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Tumor dissemination and invasive behavior are associated with a majority of cancer-related mortality cases. Loss of E-cadherin, which is caused by several tumor-promoting factors, is associated with metastasis and poor prognosis in many neoplasms. In this study, we aimed to identify small molecule compounds that restore the expression of E-cadherin, because these molecules are most likely to suppress tumor malignancy by restoring E-cadherin function and/or by inhibiting signals that suppress E-cadherin expression. Here, we developed a fluorescence screen system based on E-cadherin expression. A pilot drug library screen revealed that methotrexate (MTX) strongly induces E-cadherin expression in a colorectal cancer cell line, SW620. From the screen for 9600 compounds, we identified 9 hit compounds, which restored the expression of E-cadherin in SW620 and/or a melanoma cell line, SK-MEL-28. We confirmed that MTX and the other identified compounds transcriptionally promote E-cadherin expression. Among these, 2 compounds suppressed migration/invasion capacity in colorectal cancer cells and 3 in melanoma cells. A compound reduced SW620 migration and invasion with subtle effects on cell viability in SW620, SK-MEL-28, and a non-tumor cell line, HaCaT, with decrease in AKT and ERK1/2 protein levels. One of the other compounds reduced SK-MEL-28 cell migration and invasion and affected the viability only of SW620 and SK-MEL-28 cells but not HaCaT cells. These results suggest that these compounds would be attractive lead molecules as anti-metastasis agents., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Since the Bombyx mori genome sequence was published, conserved synteny between B. mori and some other lepidopteran species has been revealed by either FISH (fluorescence in situ hybridization) with BAC (bacterial artificial chromosome) probes or linkage analysis. However, no species belonging to the Noctuidae, the largest lepidopteran family which includes serious polyphagous pests, has been analyzed so far with respect to genome-wide conserved synteny and gene order. For that purpose, we selected the noctuid species Helicoverpa armigera and Mamestra brassicae, both with n = 31 chromosomes. Gene-defined fosmid clones from M. brassicae and BAC clones from a closely related species of H. armigera, Heliothis virescens, were used for a FISH analysis on pachytene chromosomes. We recognized all H. armigera chromosomes from specific cross-hybridization signals of 146 BAC probes. With 100 fosmid clones we identified and characterized all 31 bivalents of M. brassicae. Synteny and gene order were well conserved between the two noctuid species. The comparison with the model species B. mori (n = 28) showed the same phenomenon for 25 of the 28 chromosomes. Three chromosomes (#11, #23 and #24) had two counterparts each in H. armigera and M. brassicae. Since n = 31 is the modal chromosome number in Lepidoptera, the noctuid chromosomes probably represent an ancestral genome organization of Lepidoptera. This is the first identification of a full karyotype in Lepidoptera by means of BAC cross-hybridization between species. The technique shows the potential to expand the range of analyzed species efficiently., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

EGFR is a target protein for the treatment of non small cell lung cancer (NSCLC). The mutations associated with the activation of EGFR kinase activity, such as L858R and G719S, destabilize the inactive conformation of EGFR and are closely linked with the development of NSCLC. The additional T790M mutation reportedly causes drug resistance against the commercially available EGFR inhibitors, gefitinib and erlotinib. In this study, we searched for novel G719S/T790M EGFR inhibitors by a new in silico screening strategy, using two datasets. The results of in silico screening using protein-ligand docking are affected by the selection of 3D structure of the target protein. As the first strategy, we chose the 3D structures for in silico screening by test dockings using the G719S/T790M crystal structure, its molecular dynamics snapshots, and known inhibitors of the drug-resistant EGFR. In the second strategy, we selected the 3D structures by test dockings using all of the EGFR structures, regardless of the mutations, and all of the known EGFR inhibitors. Using each of the 3D structures selected by the strategies, 1000 compounds were chosen from the 71,588 compounds. Kinase assays identified 15 G719S/T790M EGFR inhibitors, including two compounds with novel scaffolds. Analyses of their structure-activity relationships revealed that interactions with the mutated Met790 residue specifically increase the inhibitory activity against G719S/T790M EGFR., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Anaplastic lymphoma kinase (ALK) has been in the spotlight in recent years as a promising new target for therapy of non-small-cell lung cancer (NSCLC). Since the identification of the echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion gene in some NSCLC patients was reported in 2007, various research groups have been seeking ALK inhibitors. Above all, crizotinib (PF-02341066) has been under clinical trial, and its therapeutic efficacy of inhibiting ALK in NSCLC has been reported. Among anticancer drugs, drug resistance appears frequently necessitating various kinds of inhibitors. We identified novel ALK inhibitors by virtual screening from the public chemical library collected by the Chemical Biology Research Initiative (CBRI) at the University of Tokyo, and inhibitors that are more potent were developed., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Apoptosis signal-regulating kinase 1 (ASK1, also called MAP3K5) is a mitogen-activated protein kinase kinase kinase (MAP3K) that plays important roles in stress-induced cell death and inflammation, and is expected as a new therapeutic target for cancer, cardiovascular diseases, and neurodegenerative diseases. We identified novel ASK1 inhibitors by virtual screening from the public chemical library collected by Chemical Biology Research Initiative (CBRI) at the University of Tokyo., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Tumor necrosis factor (TNF-alpha) is a pleiotropic cytokine exerting both inflammatory and cell death activity and is thought to play a role in the pathogenesis of atherosclerosis. The present study was designed to examine whether the raloxifene analogue, LY117018 could inhibit TNF-alpha-induced apoptosis in vascular endothelial cells and to clarify the involved mechanisms. Apoptosis of endothelial cells was determined by DNA fragmentation assay and the activation of caspase-3. LY117018 significantly inhibited TNF-alpha-induced caspase-3 activation and cell DNA fragmentation levels in bovine carotid artery endothelial cells. The inhibitory effect of LY117018 was abolished by an estrogen receptor antagonist ICI 182,780. p38 MAPK, JNK, ERK1/2 and Akt have been shown to act as apoptotic or anti-apoptotic signals. TNF-alpha stimulated the phosphorylation levels of p38 MAPK, JNK, ERK1/2 and Akt in vascular endothelial cells. TNF-alpha-induced apoptosis was significantly decreased by SB203580, a p38 MAPK inhibitor or SP600125, a JNK inhibitor, but was enhanced by an ERK1/2 pathway inhibitor, PD98059 or a PI3-kinase/Akt pathway inhibitor, wortmannin. The anti-apoptotic effect of LY117018 was abrogated only by PD98059 but was not affected by the inhibitors for p38 MAPK, JNK, or Akt. LY117018 stimulated the further increase in phosphorylation of ERK1/2 in TNF-alpha treated endothelial cells but it did not affect phosphorylation levels of p38 MAPK, JNK or Akt. These results suggest that LY 110718 prevents caspase-3 dependent apoptosis induced by TNF-alpha in vascular endothelial cells through activation of the estrogen receptors and the ERK1/2 signaling pathway.

A selective estrogen receptor modulator, raloxifene, has been shown to reduce cardiovascular events in relatively high-risk postmenopausal women with osteoporosis. However, the mechanisms by which raloxifene exerts a pharmacological effect on cardiovascular organs have not been fully elucidated. The present study was designed to examine whether the raloxifene analogue, 6-hydroxy-2-(p-hydroxyphenyl)-benzo(b) thien-3-yl-p-(2-(pyrrolidinyl)ethoxy phenyl ketone (LY117018), could inhibit apoptosis and to clarify the signaling pathway in vascular endothelial cells. LY117018 significantly inhibited hydrogen peroxide-induced apoptosis in bovine carotid artery endothelial cells. The anti-apoptotic effect of LY117018 was abolished by an estrogen receptor antagonist, 7alpha,7beta-(9[(4,4,5,5,5-Pentafluoropentyl)sulfinyl]nonyl) estra-1,3,5(10)-triene-3,17-diol (ICI 182,780). Mitogen-activated protein kinases (MAPK), including p38, c-Jun N-terminal kinase (JNK) and extracellular signal-regulated protein kinase1/2 (ERK1/2), and Akt, have been shown to act as apoptotic or anti-apoptotic signals. Phosphorylation of p38, JNK, ERK1/2 and Akt was examined. LY117018 increased ERK1/2 phosphorylation but did not enhance the phosphorylation of p38, JNK, or Akt. The anti-apoptotic effect of LY117018 was prevented by treatment with 2-[2'-amino-3'-methoxyphenyl]-oxanaphthalen-4-one (PD98059), an upstream inhibitor of ERK1/2. LY117018 stimulated an increase in ERK1/2 phosphorylation, which was diminished by ICI 182,780. The activation of ERK/1/2 by LY117018 was not inhibited by the transcription inhibitor, actinomycin D. These results suggest that estrogen receptors and the ERK1/2 signaling pathway are involved in the anti-apoptotic action of LY117018 in vascular endothelial cells.

Regeneration of alveolar bone is essential for periodontal treatment. Recently, cell replacement therapy has been focused on periodontal disease, but the source of the cells that regenerate alveolar bone is still uncertain. Therefore, to clarify the source of these bone-regenerating cells, we transplanted GFP-transgenic rat molars into the subcutaneous tissues of wild-type rats. Five days after transplantation, the tooth was surrounded by connective tissue containing many blood vessels. At 10 days, bone-like tissue was formed in the connective tissue between the branches of the bifurcated root. This hard tissue expanded to almost all of this bifurcation area without osseous ankylosis after 20 days. All osteoblast-like cells in the newly formed matrix were immunopositive for GFP. In addition, these cells and the peripheral cells of the matrix showed intense immunoreactivity for BMP4, Runx2, BSP, and OPN. These results demonstrate that periodontal ligament tissue contains osteoprogenitor cells that have the ability to regenerate alveolar bone. Our model suggests that these regeneration processes might be similar to normal alveolar bone formation.

To examine how fibroblast growth factor-2 (FGF-2) affects the BMP signaling pathway during bone morphogenetic protein-2 (BMP-2)-induced ectopic bone formation, we implanted type I collagen disks containing constant amounts of BMP-2 (5 micrograms) and varying amounts of FGF-2 onto the back muscles of adult male mice. We then performed histological analyses and histomorphometry, and measured bone mineral density and radiopaque area on the discs 1, 2, and 3 weeks after implantation. We also determined the expression profiles of several genes involved in bone formation and the BMP signaling pathway in the muscle that had been adjacent to the implanted disc and in muscle-derived primary culture cells that had similarly been treated with a constant concentration of BMP-2 and a varying concentration of FGF-2. In the presence of a constant amount of BMP-2, we confirmed that low doses of FGF-2 increased ectopic bone formation in vivo and high doses inhibited bone formation. Northern and/or Western blots of recovered muscle from the in vivo experiment and treated muscle-derived primary culture cells from the in vitro experiment revealed that low doses of FGF-2, but not high doses, increased the expression BMP receptor (BMPR)-1B, phosphorylated Smad1, Noggin, and Osteocalcin. Our results indicate that low-dose FGF-2 may facilitate BMP-2-induced ectopic bone formation by altering the expression of BMPRs on the surface of bone forming progenitor cells. They also indicate that the inhibitory effect of high-dose FGF-2 is not mediated via increased expression of the BMP inhibitor Noggin.

Objective: The goal of this work was to improve the mechanical strength of laser-welded gold alloy with age-hardenability at intraoral temperature., Methods: The gold alloy was cast conventionally in plate patterns (0.5 mm x 3.0 mm x 20 mm). After bench-cooling the mold to room temperature (as-cast state), transverse sections of the plate were made at mid-span. They were butted against one another and welded using Nd:YAG laser (current: 320 A; time: 10 ms; spot diameter: 1 mm). Three laser pulses were applied from both sides to cover the joint width (3.0 mm) of the specimens before or after solution heat treatment at 700 degrees C/5 min. Uncut control specimens (non-welded) were also prepared. After solution treatment, two different heat treatments were given the laser-welded specimens: high-temperature aging at 250 degrees C/15 min, or intraoral aging at 37 degrees C/3 days. Control specimens underwent all of the heat treatments after solution treatment. Tensile testing was conducted at a crosshead speed of 2 mm/min and a gauge length of 10 mm., Results: Solution treatment of the gold alloy before laser-welding did not improve the mechanical strength of laser-welded gold alloy after high-temperature aging or intraoral aging. The joint strengths of laser-welded gold alloy were improved only by solution heat treatments after laser-welding and subsequent aging treatment at high or intraoral temperatures., Significance: The results of this study indicated that laser-welded cast gold alloy prostheses aged at high or intraoral temperatures produce high strength when they are solution-treated after laser-welding.

This study examined the Hg evaporation during setting from experimental Ag-Sn-Cu alloy powders with and without Pd. Four series of alloy powders were fabricated to examine the effect on the Hg evaporation of the alloy compositions (all percentages in this report are weight percents): Pd (0-1.5), Cu (9.0-14.0), Ag (57.0-63.7), and Sn (24.9-29.5). These variations in composition produced alloy powders with gamma-Ag3Sn to beta-AgSn ratios varying from 0.0 to 23.9. The total amounts of Hg released from 10 min after trituration were measured from cylindrical specimens (4 x 8mm; n = 4 ) at 37 degrees C using a Hg vapor analyzer. The results were compared to those from commercial alloys (one high-Cu and one low-Cu alloy). All amalgams made from alloys containing 1.5% Pd exhibited lower Hg vapor release than any other amalgams, with the exception of the low-Cu amalgam. The results clearly showed that the alloy formulation affected the mercury evaporation behavior during setting of the resultant amalgams. A small addition of Pd to the alloy can produce amalgams with 50-60% less Hg vapor release during setting than a leading commercial high-Cu amalgam, Tytin.

This study characterized the corrosion behavior of cast CP titanium made with a face-coating method. Wax patterns were coated with oxide slurry of Y(2)O(3) or ZrO(2) before investing with a MgO-based investment. Three surface preparations were tested: ground, sandblasted, and as-cast. Uncoated castings served as controls. Sixteen-hour open circuit potential (OCP) measurement, linear polarization and potentiodynamic cathodic polarization were performed in an aerated modified Tani-Zucchi synthetic saliva at 37 degrees C. Anodic polarization was conducted in the same deaerated medium. Polarization resistance (R(p)) and Tafel slopes were determined. Corrosion current density was calculated for each specimen. Results (n=4) were subjected to nonparametric statistical analysis (alpha=0.05). Cross sections of cast specimens were examined by optical microscopy. Energy dispersive spectroscopy (EDS) spot analysis was performed at various depths below the surface. The OCP stabilized within several hours for all the specimens. Apparent differences in anodic polarization behavior were observed among the different surfaces. A distinctive wide passive region followed by breakdown was seen on specimens with ground and sandblasted surfaces. There were no significant differences in the corrosion resistance among the control and the two face-coating groups for each group. The Mann-Whitney test showed significantly lower OCP and higher R(p) values for ground surfaces. The surface condition significantly affected the corrosion behavior more than the face coating methods. In most cases, specimens with as-cast surfaces exhibited the least corrosion resistance during the potentiodynamic anodic polarization.

After using cast titanium prostheses in clinical dental practice, severe wear of titanium teeth has been observed. This in vitro study evaluated the wear behavior of teeth made with several cast titanium alloys containing copper (CP Ti+3.0 wt% Cu; CP Ti+5.0 wt% Cu; Ti-6Al-4V +1.0 wt% Cu; Ti-6Al-4V+4.0 wt% Cu) and compared the results with those for commercially pure (CP) titanium, Ti-6Al-4V, and gold alloy. Wear testing was performed by repeatedly grinding upper and lower teeth under flowing water in an experimental testing apparatus. Wear resistance was assessed as volume loss (mm(3)) at 5kgf (grinding force) after 50,000 strokes. Greater wear was found for the six types of titanium than for the gold alloy. The wear resistance of the experimental CP Ti+Cu and Ti-6Al-4V+Cu alloys was better than that of CP titanium and Ti-6Al-4V, respectively. Although the gold alloy had the best wear property, the 4% Cu in Ti-6Al-4V alloy exhibited the best results among the titanium metals. Alloying with copper, which introduced the alpha Ti/Ti(2)Cu eutectoid, seemed to improve the wear resistance.

Objective: The purpose of the present study was to evaluate the grindability of a series of cast Ti-Cu alloys in order to develop a titanium alloy with better grindability than commercially pure titanium (CP Ti), which is considered to be one of the most difficult metals to machine., Methods: Experimental Ti-Cu alloys (0.5, 1.0, 2.0, 5.0, and 10.0 mass% Cu) were made in an argon-arc melting furnace. Each alloy was cast into a magnesia mold using a centrifugal casting machine. Cast alloy slabs (3.5 mm x 8.5 mm x 30.5 mm), from which the hardened surface layer (250 microm) was removed, were ground using a SiC abrasive wheel on an electric handpiece at four circumferential speeds (500, 750, 1000, or 1250 m/min) at 0.98 N (100 gf). Grindability was evaluated by measuring the amount of metal volume removed after grinding for 1min. Data were compared to those for CP Ti and Ti-6Al-4V., Results: For all speeds, Ti-10% Cu alloy exhibited the highest grindability. For the Ti-Cu alloys with a Cu content of 2% or less, the highest grindability corresponded to an intermediate speed. It was observed that the grindability increased with an increase in the Cu concentration compared to CP Ti, particularly for the 5 or 10% Cu alloys at a circumferential speed of 1000 m/min or above., Significance: By alloying with copper, the cast titanium exhibited better grindability at high speed. The continuous precipitation of Ti(2)Cu among the alpha-matrix grains made this material less ductile and facilitated more effective grinding because small broken segments more readily formed.

Since dental casting requires replication of complex shapes with great accuracy, this study examined how well some commercial titanium alloys and experimental titanium-copper alloys filled a mold cavity. The metals examined were three types of commercial dental titanium [commercially pure titanium (hereinafter noted as CP-Ti), Ti-6Al-4V (T64) and Ti-6Al-7Nb (T67)], and experimental titanium-copper alloys [3%, 5% and 10% Cu (mass %)]. The volume percentage filling the cavity was evaluated in castings prepared in a very thin perforated sheet pattern and cast in a centrifugal casting machine. The flow behavior of the molten metal was also examined using a so-called "tracer element technique." The amounts of CP-Ti and all the Ti-Cu alloys filling the cavity were similar; less T64 and T67 filled the cavity. However, the Ti-Cu alloys failed to reach the end of the cavities due to a lower fluidity compared to the other metals. A mold prepared with specially designed perforated sheets was effective at differentiating the flow behavior of the metals tested. The present technique also revealed that the more viscous Ti-Cu alloys with a wide freezing range failed to sequentially flow to the end of the cavity., (Copyright 2003 Elsevier Science Ltd.)

Objectives: This study evaluated the mechanical properties of cast Ti-Cu alloys with the hope of developing an alloy for dental casting with better mechanical properties than unalloyed titanium., Methods: Ti-Cu alloys with five concentrations of copper (0.5, 1.0, 2.0, 5.0 and 10.0 mass%) were made in an argon-arc melting furnace. The alloys were cast into magnesia-based molds using a centrifugal casting machine. The microstructure, microhardness profile of the specimen cross section, tensile strength, yield strength, and elongation were determined for the castings. Scanning electron microscope fractography was undertaken for the fractured surfaces after tensile testing. XRD was performed on the polished specimens. Results were analyzed using one-way ANOVA and the Student-Newman-Keuls tests., Results: The mean tensile strengths of all the cast Ti-Cu alloys were significantly (p<0.05) higher than for cast commercially pure titanium (CP Ti). Of the Ti-Cu alloys tested, the 5 and 10% Cu alloys had significantly higher strength than the rest. The 10% Cu alloy exhibited the lowest mean elongation. CP Ti and the 0.5 and 1% Cu alloys showed higher ductility. The bulk hardness of all the cast Ti-Cu alloys, except for the 10% Cu alloy, and CP Ti was approximately the same., Significance: By alloying with copper, the cast titanium became stronger. Increases in the tensile strength (30%) and yield strength (40%) over CP Ti were obtained for the 5% Cu alloy. Elongation was approximately 3%, which was similar to cast Ti-6Al-4V. Ti-Cu alloys, such as the 5% Cu alloy, could be used for prosthetic dental applications if other properties necessary for dental castings are obtained.

A reaction layer forms on cast titanium alloy surfaces due to the reaction of the molten metal with the investment. This surface layer may affect the corrosion of the alloy in the oral environment. The objective of this study was to characterize the in vitro corrosion behavior of cast titanium alloys. ASTM Grade 2 CP titanium, Ti-6Al-4V, Ti-6Al-7Nb and Ti-13Nb-13Zr alloys were cast into a MgO-based investment. Experiments were performed on castings (N=4) with three surface conditions: (A) as-cast surface after sandblasting, (B) polished surface after removal of the reaction layer, and (C) sandblasted surface after removal of the reaction layer. Open-circuit potential (OCP) measurement, linear polarization, and potentiodynamic cathodic polarization were performed in aerated (air+10% CO(2)) modified Tani-Zucchi synthetic saliva at 37 degrees C. Potentiodynamic anodic polarization was subsequently conducted in the same medium deaerated with N(2)+10% CO(2) gas 2 h before and during the experiment. Polarization resistance (R(P)) and corrosion rate (I(CORR)) were calculated. Numerical results were subjected to nonparametric statistical analysis at alpha=0.05. The OCP stabilized for all the specimens after 6 x 10(4)s. Apparent differences in anodic polarization were observed among the different surfaces for all the metals. A passivation region followed by breakdown and repassivation were seen on specimens with surfaces A and C. An extensive passive region was observed on all the metals with surface B. The Kruskal-Wallis test showed no significant differences in OCP, R(p), I(CORR) or break down potential for each of the three surfaces among all the metals. The Mann-Whitney test showed significantly lower R(P) and higher I(CORR) values for surface C compared to the other surfaces. Results indicate that the surface condition has more effect on corrosion of these alloys than the surface reaction layer. Within the oxidation potential range of the oral cavity, all the metal/surface combinations examined showed excellent corrosion resistance.

Objective: Studies have been performed using high- and low-copper amalgams to measure the amounts of mercury dissolution from dental amalgam in liquids such as artificial saliva; however, in most cases, mercury dissolution has been measured under static conditions and as such, may be self-limiting. This study measured the mercury release from low- and high-copper amalgams into flowing aqueous solutions to determine whether the total amounts of dissolution vary under these conditions when tested at neutral and acidic pH., Methods: High- and low-copper amalgam specimens were prepared and kept for 3 days. They were then longitudinally suspended in dissolution cells with an outlet at the bottom. Deionized water or acidic solution (pH1) was pumped through the cell. Test solutions were collected at several time periods up to 6 days or 1 month and then analyzed with a cold vapor atomic absorption spectrophotometer. After dissolution testing, the specimens were examined using SEM/XEDA for any selective degradation of the phases in the amalgam., Results: Except for the high-copper amalgam in the pH1 solution, the dissolution rates were found to decrease exponentially with time. The rate for the high-copper amalgam in pH1 solution slowly increased for 1 month. The total amounts (microgram/cm(2)) of mercury released over 6 days or 1 month from both types of amalgam in deionized water were not significantly different (p>/=0.05). The high-copper amalgam released significantly more mercury than the low-copper amalgam in the pH1 solution at both time periods. For both amalgams, the dissolution in pH1 was significantly higher than in deionized water., Significance: Mercury dissolution from amalgam under dynamic conditions is enhanced in an acidic media, and most prominently for a high-copper formulation.

Pure titanium and titanium alloys are potential materials for the fabrication of cast dental appliances. One important factor in producing sound castings is the capacity of the metal to fill the mold. This study used a wedge-shaped mold to compare the mold filling of titanium with that of conventional dental casting alloys. The metals used were CP Ti, Ti-6Al-7Nb, Ti-6Al-4V, Ti with 1 and 4wt% Cu and ADA Type III gold alloy and an Ni-Cr alloy. The castings were cut into four pieces parallel to the triangular surface. Mold filling was evaluated as the distance between the tip of the cast wedge and theoretical tip of the triangle. The mold filling of the gold alloy was superior compared to all the metals tested, while the mold filling of the Ni-Cr alloy was the worst. There were no statistical differences at the 30 degrees marginal angle for all the cast titanium metals. At the sharper 15 degrees angle, CP Ti and Ti-6Al-7Nb was superior to both the Ti-Cu alloys. Although the mold filling of titanium was inferior compared to the gold alloy, the data justify the use of titanium for the production of dental appliances.

Objective: The aim of this study was to investigate the effect of various heat treatments on the mechanical properties of gold alloys capable of age-hardening at intraoral temperature., Methods: Dumbbell-shaped patterns (ISO 6871) were cast with three gold alloys (Sofard; NC Type-IV; Aurum Cast, NihombashiTokuriki Co.). The Sofard alloy is age-hardenable at intraoral temperature. The castings underwent various heat treatments [as-cast (AC); solution treatment (ST); high-temperature aging (HA); intraoral aging (IA)]. After these heat treatments, ultimate tensile strength (UTS), 0.2% offset yield strength (YS), and elongation (EL) were measured at a strain rate of 1.7x10(-4)/s. Fracture surfaces of the specimens after tensile testing were observed using SEM. Vickers hardness was also measured after heat treating., Results: After IA, the hardness values of the Sofard alloy increased and reached values similar to the hardness of the Sofard specimens aged at high temperature (HA). The hardness values of the NC Type-IV and Aurum Cast specimens slightly increased after IA, but did not reach the values of the specimens after HA. All the Sofard, NC Type-IV and Aurum Cast specimens showed significantly (P<0.05) greater hardness values after HA, compared with the values after any other heat treatments (AC, ST and IA). The UTS and YS of the specimens indicated a tendency similar to the results obtained for hardness. The Sofard specimens with ST showed the greatest elongation compared to the corresponding NC Type-IV and Aurum Cast specimens. However, the elongation of the Sofard specimens was abruptly reduced after intraoral aging., Conclusion: Intraoral aging significantly improved the mechanical properties and hardness of the Sofard alloy.

The purpose of this study was to investigate the bond strength between porcelain and experimental cast titanium alloys. Eleven binary titanium alloys were examined: Ti-Cr (15, 20, 25 wt%), Ti-Pd (15, 20, 25 wt%), Ti-Ag (10, 15, 20 wt%), and Ti-Cu (5, 10 wt%). As controls, the bond strengths for commercially pure titanium (KS-50, Kobelco, Japan) and a high noble gold alloy (KIK, Ishifuku, Japan) were also examined. Castings were made using a centrifugal casting unit (Ticast Super R, Selec Co., Japan). Commercial porcelain for titanium (TITAN, Noritake, Japan) was applied to cast specimens. The bond strengths were evaluated using a three-point bend test according to ISO 9693. Since the elastic modulus value is needed to evaluate the bond strength, the modulus was measured for each alloy using a three-point bend test. Results were analyzed using one-way ANOVA/S-N-K test (alpha = 0.05). Although the elastic moduli of the Ti-Pd alloys were significantly lower than those of other alloys (p = 0.0001), there was a significant difference in bond strength only between the Ti-25Pd and Ti-15Ag alloys (p = 0.009). The strengths determined for all the experimental alloys ranged from 29.4 to 37.2MPa, which are above the minimum value required by the ISO specification (25 MPa).

Objectives: A reaction layer forms on cast titanium surfaces due to the reaction of the molten titanium with the investment material. Such a layer prevents strong adhesion between titanium and porcelain. This study characterized the effects of surface modifications on cast titanium surfaces and titanium-ceramic adhesion., Methods: ASTM grade II CP titanium was cast into an MgO-based mold. Castings were devested by sandblasting with alumina particles, and subjected to surface modification by immersion in one of the following solutions: (1) 35% HNO3-5% HF at room temperature for 1min; (2) 50% NaOH-10% CuSO4 x 5H2O at 105 degreesC for 10min; (3) the NaOH-CuSO4 solution followed by the HNO3-HF solution; (4) 50% NaOH-10% NaSO4 at 105 degreesC for 10 min; (5) the NaOH-NaSO4 solution followed by the HNO3-HF solution; and (6) 50% NaOH solution at 105 degreesC for 10min. Surfaces only sandblasted with alumina were used as controls. Specimen surfaces were characterized by XRD and SEM/EDS, and hardness-depth profiles were determined. All specimens were sandblasted with 110 microm alumina particles before porcelain firing. An ultra-low-fusing porcelain (Vita Titankeramik) was fused on the titanium surfaces. The titanium-ceramic adhesion was characterized by a biaxial flexure test, and area fraction of adherent porcelain (AFAP) was determined by X-ray spectroscopy., Results: EDS analyses revealed a substantial amount (13-17 wt%) of Al on the control, and specimens modified with Methods 2, 4, and 6. XRD revealed residual stress in the titanium surfaces and corundum on the control, and Methods 2, 4, and 6 specimens. A new Ti(Cu, Al)2 phase was identified on the titanium surfaces modified by immersion in 50% NaOH-10% CuSO4 x 5H2O aqueous solution. Reduced residual stress was observed on Method 1, 3, and 5 specimens. No corundum peaks were detected on these specimens. Compared to the control, significantly lower (P < 0.05) hardness values were found for Methods 1-3 and Method 5 specimens at 20 microm below the surfaces and for Method 1-5 specimens at 50 microm below the surfaces. Significantly higher (P < 0.05) AFAP values were found for surfaces modified with Methods 2-6 compared to the control and Method 1, and no significant differences were found among Methods 1-6, and between control and Method 1., Significance: Based on the results from the present study, porcelain adherence to cast CP titanium can be improved by the caustic baths used in the study.

Objective: The purpose of this study was to investigate the cutting efficiency of air-turbine burs on cast free-machining titanium alloy (DT2F) and to compare the results with those for cast commercially pure (CP) Ti, Ti-6Al-4V alloy, and dental casting alloys., Methods: The cast metal (DT2F, CP Ti, Ti-6Al-4V, Type IV gold alloy and Co-Cr alloy) specimens were cut with air-turbine burs (carbide burs and diamond points) at air pressures of 138 or 207 kPa and a cutting force of 0.784 N. The cutting efficiency of each bur was evaluated as volume loss calculated from the weight loss cut for 5 s and the density of each metal. The bulk microhardness was measured to correlate the machinability and the hardness of each metal., Results: The amounts of DT2F cut with the carbide burs were significantly (p < 0.05) greater than for the other titanium specimens at either 138 or 207 kPa. The diamond points exhibited similar machining efficiency among all metals except for Type IV gold alloy. The increase in the volume loss of Co-Cr alloy (Vitallium) cut with the diamond points showed a negative value (-29%) with an increase in air pressure from 138 to 207 kPa. There was a negative correlation between the amounts of metal removed (volume loss) and the hardness (r2 = 0.689) when the carbide burs were used., Significance: The results of this study indicated that a free-machining titanium alloy (DT2F) exhibited better machinability compared to CP Ti and Ti-6Al-4V alloy when using carbide fissure burs. When machining cast CP Ti and its alloys, carbide fissure burs possessed a greater machining efficiency than the diamond points and are recommended for titanium dental prostheses.

Substance P plays an important role in neurogenic inflammation with granulocyte infiltration. To investigate cytokines involved in the substance P-induced inflammation and the mechanism of cell activation, we studied the release of TNF (tumor necrosis factor)-alpha and histamine from human skin slices in response to substance P and antigen. Substance P induced the release of histamine and TNF-alpha in a dose-dependent manner at concentrations from 0.8 to 100 microM. PD 098059 (2'-amino-3'-methoxyflavone) selectively inhibited the release of TNF-alpha, but not the release of histamine induced by either substance P or antigen. SB 203580 ([4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-++ +imida zole]) slightly inhibited TNF-alpha release induced by antigen, but not that induced by substance P, and slightly enhanced histamine release induced by either stimulation. The release of TNF-alpha in response to either stimulation was inhibited by 1 nM-1 microM dexamethasone, but histamine release was not affected. These results suggest that substance P, in addition to antigen, induced TNF-alpha release from human skin by a mitogen-activated protein (MAP) kinase, predominantly extracellular signaling-regulated protein kinase (ERK)-dependent, and dexamethasone-sensitive pathway, which is separate from that for histamine release from mast cells.

This study investigated the machinability (ease of metal removal) of commercially pure (CP) titanium and Ti-6Al-4V alloy. Both CP Ti and Ti-6Al-4V were cast into magnesia molds. Two types of specimens (with alpha-case and without alpha-case) were made for CP Ti and Ti-6Al-4V. Machinability (n = 5) was evaluated as volume loss (mm3) by cutting/grinding the 3.0 mm surface using fissure burs and silicon carbide (SiC) under two machining conditions: (1) two machining forces (100 or 300 gf) at two rotational speeds (15000 or 30000 rpm) for 1 min, and (2) constant machining force of 100 gf and rotational speed of 15000 rpm for 1, 2, 5, 10, and 30 min. As controls, conventionally cast Co-Cr and Type IV gold alloys were evaluated in the same manner as the titanium. When fissure burs were used, there was a significant difference in the machinability between CP titanium with alpha-case and without alpha-case. On the other hand, there was no appreciable difference in the amount of metal removed for each tested metal when using the SiC points.

Objectives: Although the advent of orthotopic lower urinary reconstruction in women is a major achievement in the evolution of urinary diversion, the mechanism of voiding dysfunction remains incompletely understood. We report on the voiding function of ileal neobladder in 12 female patients., Methods: A neobladder was constructed using an ileal segment. Voiding function was evaluated in terms of voiding pattern and continence. Chain cystography was performed postoperatively to detect the existence of urethral angulation. Median follow-up was 33.2 months (range 8.4 to 77.4)., Results: Of the 1 2 patients, 10 (83.3%) achieved excellent daytime continence, and 6 (50%) had nighttime incontinence despite regular voiding during the night. Three patients (25%) sometimes or often performed self-catheterization because of difficulty in urinating. One patient (8.3%) was unable to void and required regular intermittent catheterization. Chain cystogram revealed urethral angulation in the 3 patients with difficulty in urinating or hypercontinence., Conclusions: An orthotopic neobladder can be constructed in women with excellent functional results. Urethral angulation appears to be one of the main mechanisms for voiding dysfunction, and further studies on the functional anatomy of the female urethra are needed to improve the voiding function of the orthotopic neobladder in women.

Objective: The aim of this study was to determine if Hg vaporization during setting and after abrasion of amalgams could be reduced by adding indium to Hg prior to trituration., Methods and Materials: Hg-In alloys (0,5,10,15 wt% In) were triturated with commercial amalgam alloys (Tytin, Kerr; Artalloy, Degussa; Sybraloy, Kerr) and condensed into cylinders (4 x 8 mm). In one experiment, Hg release during setting was measured in air (37 degrees C) with a Jerome 431 Hg analyzer (n = 4). In a second experiment, amalgams aged two months were uniformly abraded on wet #600 SiC, blotted dry, and Hg release was measured in air (22 degrees C) for 30 min with a Jerome 411 Hg analyzer (n = 6). Total Hg was determined by integration (ng/mm2). Results were compared by ANOVA and Tukey's test (alpha = 0.05)., Results: Indium reduced Hg release from amalgams during setting. Amalgams ceased Hg release within 5 h. Indium did not reduce Hg release from abraded, set amalgams except Artalloy w/15% In., Significance: Coupled with our previous studies, this work shows that 5-15 wt% indium can be added to effectively reduce Hg release during setting, but not after abrasion of set amalgams.

The corrosion of cast or milled ASTM Grade II CP titanium with different surface conditions was studied by potentiodynamic anodic polarization and immersion testing. Specimens were fabricated using three dental titanium casting systems and from machined titanium. Three surface conditions were tested: (1) sandblasted with surface reaction layers remaining; (2) polished surface without surface reaction layers; and (3) sandblasted surface without surface reaction layers. An acidic saline solution (0.1 M lactic acid/0.1 M NaC1 [pH = 2]) and an artificial saliva were used as the corrosion media. Anodic polarization was performed starting at 50 mV below the rest potential and terminating at +2250 mV vs Ag/AgCl. Two surface conditions (sandblasted with the surface reaction layers and polished without such layers) were examined in the immersion test. Specimens were immersed in the corrosion media at 37 degrees C for six months. The recovered solution was analyzed by an atomic absorption spectrophotometer for titanium dissolution. A distinctive passive region on the polarization diagram, ranging from approximately 0 to approximately +1300 mV, was observed for all specimens in both media. Great similarity was observed for all the sandblasted specimens which had larger primary passive current densities and passive regions compared to the polished ones. A current density peak at approximately +1600 mV seen for all the specimens with sandblasted surfaces was less well defined for the polished specimens. Immersion testing in the acidic saline solution revealed no significant differences among the polished specimens. A significant increase (P < 0.05) in titanium dissolution was found for the sandblasted specimens with surface reaction layers remaining on the surfaces made with phosphate-bonded SiO2/Al2O3 investment compared to the polished ones. Significant differences were also found between sandblasted specimens with the surface reaction layers resulting from different investment materials and different casting methods. Measurable amounts of titanium were not found for all specimens in the artificial saliva after six months. It is evident that the corrosion behavior of cast CP titanium is similar to that of machined titanium. The surface roughness appears to be a more prominent factor than do the surface reaction layers on the polarization behavior of the CP titanium under the present experimental conditions. Surface roughness and the presence of the surface reaction layers both affect the dissolution of titanium.

Objective: Mercury vapor release from amalgams during setting significantly decreases when the amalgams are prepared with binary Hg-In liquid alloys. The objective of this study was to compare the cytotoxicity of amalgams made with experimental Hg-In alloys with that of amalgam without In and a commercial In-containing amalgam., Methods: Amalgam specimens were prepared by triturating a high-Cu alloy powder (Tytin, Kerr) with pure Hg or Hg-In liquid alloy containing 5, 20 or 50% In and also by triturating an In-containing high-copper alloy powder (Indiloy, Shofu) with pure Hg. After the specimens were aged for 2 wk, a cylindrical specimen of each amalgam was immersed consecutively in cell culture medium for 0-8, 8-48 and 48-72 h. The cytotoxicity of the extracts was determined by placing them in contact with Balb/c 3T3 mouse fibroblasts for 24 h, after which the succinic dehydrogenase (SDH) activity was measured and expressed as a percentage of the Teflon negative controls. The results were statistically compared using ANOVA and Tukey's test (alpha = 0.05). The concentration of elements released into the extracts was determined by atomic absorption spectrophotometry and evaluated by Kruskal-Wallis and nonparametric multiple comparisons., Results: For the 0-8 h and 8-48 h intervals, the 20% In amalgam was significantly (p < 0.05) less toxic than the other amalgams, and not different from the Teflon control. Results for the other amalgams were only slightly depressed compared to the Teflon control. For the 48-72 h interval, all amalgams were essentially no different from the control. Copper was the element dominantly released into the medium from all the amalgams tested., Significance: For amalgam tested after aging, alloying indium to mercury did not deleteriously affect the cytotoxicity of the resultant amalgam compared to the amalgam without indium.

Objectives: This study used cyclic voltammetry to examine the effect of the composition of dental amalgams on their electrochemical behavior, including reactions occurring outside of oral conditions., Methods: Amalgams (residual mercury 47.5%) were prepared using two low-copper (3 wt% Cu) powders and five high-copper powders (40-80 wt% Ag, 12-30 wt% Cu) with and without zinc (1.5 wt%). Cyclic voltammograms were obtained at 37 degrees C in 1.0% NaCl scanning at 2 mV/s in the potential range from -1.5 V to +0.8 V vs. Ag/AgCl., Results: During the anodic scans, AgCl and Hg2Cl2 films were formed on all amalgams except the one with only 40 wt% Ag. In all high-copper amalgams, a prominent Cu (oxidation) peak was found at -0.1 V, indicating the release of copper during corrosion. Zinc affected the oxidation process for both low- and high-copper amalgams. When zinc was absent, a peak for Sn2+ oxidation appeared at -0.4 V. When zinc was present, a Sn4+ oxidation peak was revealed at -0.6 V. In some amalgams, there was evidence of the selective corrosion (pitting corrosion) of tin and copper. In the lowest silver-content amalgam, no protective films were formed, which is indicative of its poor corrosion resistance. As expected, in all the low-copper amalgams, an extreme increase in current density was recorded immediately at 0 V, due to the release of tin from gamma 2., Significance: Cyclic voltammetry is useful for the rapid examination (less than an hour) of the electrochemical behavior of amalgams, specifically to obtain information on the formation of compounds and the sequences of electrochemical reactions.

Objective: Finding an optimal soldering system for a titanium prosthesis has become increasingly important with the successful introduction of titanium and titanium alloys to dentistry. This study examined the effect of corrosion on the strength of the soldered joints of pure titanium and Ti-6Al-4V alloys joined using various solders., Methods: Commercially pure titanium and Ti-6Al-4V alloy rods (2 mm in diameter; 25 mm long) were soldered in an argon atmosphere using four solders: two kinds of titanium-based solder, a gold-based solder, and a silver-based solder. Tensile strengths were examined before or after immersion treatments. Specimens were immersed in either a 0.9% NaCl or 1.0% lactic acid solution held at 35 degrees C for 3 and 8 wk. The amounts of various metal elements released were determined by atomic absorption photospectroscopy. The natural potentials and potentiodynamic polarization behavior of the soldered specimens in 0.9% NaCl or 1.0% lactic acid were determined by a computer-assisted corrosion measurement system. The results were analyzed by ANOVA and Student's t-test., Results: The cp-titanium and Ti-6Al-4V samples soldered with titanium-based solders exhibited tensile strengths of 300-400 MPa and were not significantly affected by immersion in either solution (no significant difference at p < 0.05). The strengths of both the cp-titanium and titanium alloy specimens soldered with gold-based solder were significantly lower than for any of the other specimens and were affected by immersion in the 0.9% NaCl solution (p < 0.01). The cp-titanium and Ti-6Al-4V specimens that were soldered with titanium-based solders did not show any transpassive regions or breakdown in the natural electrode potential range. On the contrary, the specimens soldered with gold-based and silver-based solders showed transpassive regions or breakdown potentials at less than 0 mV in 0.9% NaCl solution., Significance: It is recommended that titanium-based solder be employed for titanium and titanium alloys.

Objectives: This study evaluated the mechanical properties under static and cyclic loading conditions of various types of glass ionomers used for bases and core build-ups under restorations., Methods: Compressive strength and three-point flexural strength of two different glass ionomers and two metal-reinforced glass ionomers were determined 1 d after the start of mixing. The flexural fatigue resistance of these materials was measured in the load range of 650 g to 1050 g using a three-point bending machine, and fractured surfaces of the specimens were examined using SEM., Results: All the glass ionomers exhibited similar compressive and flexural strengths. The results analyzed by Cox' proportional hazard model demonstrated that the admixed-type metal-reinforced glass ionomer had the highest fatigue resistance, while the water-hardening glass ionomer had the lowest fatigue resistance among the materials examined (p<0.5)., Significance: There was no significant improvement in the static mechanical properties from incorporating metal particles into the glass ionomers. However, the addition of metal particles as in the admixed-type metal-reinforced glass ionomer produced a material with increased fatigue resistance.

Objectives: This study was conducted to determine the effect of zinc in amalgam on the static mechanical properties and resistance to fatigue-crack propagation of amalgams., Methods: Fatigue, creep, compressive and flexure tests were performed on high-Cu Dispersalloy (Johnson and Johnson Dental Products Co., East Windsor, NJ, USA) and low-Cu Velvalloy (S.S. White Dental Products Int., Philadelphia, PA, USA) in both Zn-containing and Zn-free formulations. Linear Elastic Fracture Mechanics principles were used to characterize the fatigue behavior (crack lengths were monitored)., Results: The incorporation of Zn into these amalgams significantly improved their fatigue and creep resistance, while the effect of Zn on the static compressive and flexure strengths was not consistent. Zn significantly increased (p < 0.05) the resistance to fatigue crack propagation during Stage II crack growth for both amalgams, and increased the variations in crack velocity for a given stress intensity difference, without visibly altering the path or nature of the fatigue cracks. Possible influences on fatigue behavior were the mixed microstructure (particles and matrix), the nature of the crack tip, and creep., Significance: The superior resistance to tensile fatigue crack propagation of amalgams containing small amounts of Zn (approximately 1 wt%) in vitro compared with amalgams with no Zn correlated with the superior resistance to marginal breakdown in vivo of Zn-containing amalgams. The range of stress intensities over which stable cracks could propagate was small, while the large variations observed in fatigue crack growth rates for individual materials invalidate predicting a unique fatigue life from the empirical equations obtained.

Objectives: An in vitro screening test was used to compare the cytotoxicity and elemental release from mercury- and gallium-based dental restorative materials., Methods: The test employed three sequential extractions of the samples into cell-culture medium which were then used to evaluate the cytotoxicity of the samples and the release of elements from the samples. Cytotoxicity was measured by placing the extract in contact with Balb/c mouse fibroblasts for 24 h and measuring the succinic dehydrogenase activity of the cells. The release of elements was measured by means of atomic absorption spectrophotometry., Results: Samples of Tytin (Kerr) showed no cytotoxicity compared to Teflon controls. Dispersalloy (Johnson and Johnson) was severely cytotoxic initially when Zn release was greatest, but was less toxic between 48 and 72 h as Zn release decreased. Gallium Alloy GF (Tokuriki Honten) was moderately cytotoxic after 8 h, and increased in cytotoxicity thereafter, which correlated with a substantial and persistent release of Ga from this material., Significance: The results of the current study concurred with in vivo assessments of these materials, and the use of sequential extractions was useful in determining trends in the cytotoxicity and elemental release from these materials.

The release of mercury from two freshly triturated amalgams exposed to a reducing atmosphere, hydrogen, was quantitated at three different temperatures. A low-copper and a high-copper amalgam were placed into a flowing hydrogen gas atmosphere for 60 min after trituration, and then the hydrogen was replaced by compressed air. The results were compared to those obtained in a previous study in which air and argon atmospheres were used under identical conditions. At 37 degrees C, the rate of evaporation of mercury from the amalgams was similar when they were exposed to hydrogen before being exposed to air. During exposure to hydrogen, the evaporation rate appeared to exceed the limit of the gold film mercury analyzer (284 pg/mm2/s), but was rapidly reduced upon exposure to air. The results were identical to those from argon exposure. When the same experiment was performed at 80 degrees C, the evaporation rate after hydrogen exposure was greater than that after exposure to argon, and far greater than that during exposure to air alone. Similar results were achieved at 110 degrees C, but there was less difference between hydrogen and argon exposure. The results support previous studies which show that the evaporation of mercury from amalgam is mainly limited by the formation of an oxide film.

Biphasic calcium phosphate ceramics consist of both beta-tricalcium phosphate and hydroxyapatite. This study was performed to examine the in vitro stability of biphasic calcium phosphate ceramics in deionized distilled water and in physiological solutions. Biphasic calcium phosphates of two different molar ratios and pure hydroxyapatite and pure beta-tricalcium phosphate granules were tested. X-ray diffraction data were obtained before and after immersion. Surface morphology was compared using scanning electron microscopy. The pure beta-tricalcium phosphate and the beta-tricalcium phosphate in the biphasic calcium phosphate ceramics gradually converted to apatite. Needle-like apatite crystals were observed on the surface of biphasic calcium phosphate and beta-tricalcium phosphate, but hydroxyapatite showed no change.

An in vitro method is described in which measurements were made of the total amount of mercury vapor released from three types of amalgam during routine dental procedures. It was found that the greatest amount of mercury was released during dry polishing of one amalgam (44 micrograms). Removal of amalgam from a Class I cavity under water spray and high volume evacuation also generated large amounts of mercury as expected (15-20 micrograms). However, under the more clinically relevant conditions of extending evacuation for one minute to remove residual amalgam and mercury after cutting, this value was reduced by approximately 90%. The total amount of mercury generated during placement (6-8 micrograms), wet polishing (2-4 micrograms) and trituration (1-2 micrograms) were also measured. The study showed that dental procedures associated with amalgam do potentially expose the patient and operator to mercury vapor. However, the total amount of mercury released during any procedure was far below the total exposure level calculated from the daily threshold limits established by regulatory agencies for occupational exposure.

We examined the distribution of synapsin I in the gerbil brain and investigated ischemic damage of presynaptic terminals immunohistochemically by using this protein as a marker protein of synaptic vesicles. The reaction for synapsin I in normal gerbil brain is exclusively localized in the neuropil, and other brain structures such as neuronal soma, dendrites, axon bundles, glia and endothelial cells exhibited little immunoreactivity. In a reproducible gerbil model of unilateral cerebral ischemia, ischemic loss of synapsin I immunoreactivity in the affected hemisphere was confined to the area exhibiting overt infarction, where the breakdown of this protein was also confirmed by the immunoblot analysis, and noted much later than that of microtubule-associated protein 2 immunoreactivity, which was demonstrated in neuronal soma and dendrites. In the non-affected hemisphere, selective damage of presynaptic terminals due to Wallerian degeneration and subsequently occurring resynaptogenesis at the molecular layer of the dentate gyrus were clearly demonstrated as a loss and recovery of immunoreaction for synapsin I, respectively. In a gerbil model of bilateral cerebral ischemia, immunoreaction for synapsin I was persistently preserved after seven days to two months recirculation following a brief period of global forebrain ischemia in the CA1 region of the hippocampus, where delayed neuronal death was consistently observed.(ABSTRACT TRUNCATED AT 250 WORDS)

In comparison with haemagglutinin (HA)-active strains of Bordetella bronchiseptica, the HA-deficient strains lacked a 150 kDa protein band on SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Adsorption of partially purified HA with bovine erythrocytes showed the loss of the 150 kDa band in the supernatant. This 150 kDa protein was purified by high-performance liquid chromatography using gel filtration columns. Electron microscopic examination revealed that the purified HA possessed a fine filamentous structure with dimensions of approximately 2 x 150 nm, which was considered to represent the filamentous haemagglutinin of B. bronchiseptica. Both the cell-free antigen obtained from the culture supernatant of phase-I strain of the bacteria and the bovine erythrocytes, which combined with crude HA showed an excellent protective activity of the challenge by virulent strain of B. bronchiseptica in mice.

The purpose of this study was to compare the relative cytotoxicity of amalgams, alloys, and their constituent elements and phases, by means of a rapid and sensitive in vitro cell culture test. Pure copper and zinc showed intensive cytotoxicity, significantly greater than that of pure silver and mercury. Pure tin was non-cytotoxic. The gamma-one phase (Ag2Hg3) revealed moderate cytotoxicity, which was significantly decreased by the addition of 1.5% and 5% Sn. However, the addition of 1.5% Zn to gamma 1 containing 1.5% Sn dramatically increased the cytotoxicity of gamma 1 to the same level as that of pure zinc. Whenever zinc was present in amalgams, higher cytotoxicity was revealed. High-copper amalgams showed the same cytotoxicity as a zinc-free low-copper amalgam. The addition of selenium did not reduce the cytotoxicity of amalgam. The cytotoxicity of amalgams was reduced after 24 h. The results of this study suggest that the major contributor to the cytotoxicity of alloy for amalgam is probably copper, while that for amalgam is zinc.

The dynamic mechanical properties of two high-copper amalgams (Tytin and Dispersalloy) and two traditional amalgams (Aristalloy and Aristalloy with Zn) were measured over a temperature range of 0-70 degrees C and at frequencies of 0.1, 1, and 10 Hz by means of a DuPont DMA. Values of storage modulus (E') for the amalgams were equivalent to the Young's modulus (E) measured from static mechanical test methods, with Dispersalloy demonstrating the highest moduli. Values of E' decreased with increased temperature. E' of traditional amalgams decreased more rapidly than did those of the Cu-rich amalgams. Values of loss modulus (E") for Tytin were smaller than those of Dispersalloy and the two types of Aristalloy. High values of E" for the traditional amalgams correspond to a greater viscous behavior. Marked differences between the magnitude of tan delta and its temperature coefficients for traditional and high-copper amalgams were observed, which is indicative of differences in visco-elastic behavior between these two amalgam systems.

Several manipulative variables have been shown to influence the physical properties of dental amalgam. Variation in trituration time has been reported to affect creep, compressive strength, and diametral tensile strength in various amalgams. Recent classification of amalgam alloys by particle microstructure reveals four categories: single-composition lathe-cut; single-composition spherical; lathe-cut and eutectic admixture; and lathe-cut and single-composition spherical admixture. The effect of variation of trituration times has not been studied for these newer high-copper alloys. A representative from each classification was selected and physical properties tested, with varied times for trituration utilized. Results showed little compromise in laboratory values for the properties tested. Additional laboratory and clinical trials are warranted, but this study supports the premise that clinicians may vary trituration time to improve handling characteristics without significantly affecting mechanical properties.