Measurement of exothermic heat released during polymerization of a lightcuring composite resin: Comparison of light irradiation modes.

High-power light-curing units have emerged that reduce the time of procedures in dental clinical work. However, patients sometimes complain of pain during the polymerization of composite resin. In this experiment, we investigated how differences in light-curing mode affect the temperature rise during composite resin polymerization in vitro. Light-curing mode conditions were divided into four groups: 3 s in plasma mode (Plm3) and 5, 10, and 20 s in standard mode. The temperature curve under Plm3 exhibited a rapid increase during the first 3 s of light curing before reaching a maximum of around 55°C. In contrast, the temperature rose rapidly but less sharply for irradiation in each standard mode compared with Plm3. These results suggest that irradiation using a high-power mode increases the temperature at an excessively high rate, and this may raise concern about side effects on the pulp.

Leaching behaviors of computer-aided design/computer-aided manufacturing composite resin component elements immersed in water.

PURPOSE: Immersion tests in purified water were conducted to evaluate the leaching behaviors of filler elements contained in computer-aided design/computer-aided manufacturing (CAD/CAM) composite resin. METHODS: Four commercial CAD/CAM resin composite blanks were tested: Shofu block HC 2 layer, Cerasmart, Katana Avencia block, and KZR-CAD HR Block 2. The specimens in the size of 10.0×12.0×2.0mm were immersed in a 50-mL conical tube containing 40mL of purified water, and then placed in a constant-temperature oven set at a temperature of 37, 60, 70, or 80°C and stored statically for 30 days. After storage, the concentrations of leached elements in the immersion solution were measured with an inductively coupled plasma atomic emission spectrometer. To characterize the surface of the specimen after the immersion test, secondary electron images were obtained. RESULTS: The immersion test resulted in the leaching of Si, the main component, from all materials tested. Some materials were found to have leached high amount of Ba or Sr in addition to Si, and remarkable surface degradation was observed. The amount of leached elements increased with increased immersion temperatures. CONCLUSIONS: Filler elements in CAD/CAM composite resins used in this study leached into purified water. The leached elements and its quantities greatly differed among materials and depend on the types of the oxides composing the filler. The amounts of leached elements varied in a temperature-dependent manner.

Anti-angiogenic and anti-tumor effects of TAK-593, a potent and selective inhibitor of vascular endothelial growth factor and platelet-derived growth factor receptor tyrosine kinase.

We recently reported that TAK-593, a novel imidazo[1,2-b]pyridazine derivative, is a highly potent and selective inhibitor of the vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) receptor tyrosine kinase families. Moreover, TAK-593 exhibits a uniquely long-acting inhibitory profile towards VEGF receptor 2 (VEGFR2) and PDGF receptor ß (PDGFRß). In this study, we demonstrated that TAK-593 potently inhibits VEGF- and PDGF-stimulated cellular phosphorylation and proliferation of human umbilical vein endothelial cells and human coronary artery smooth muscle cells. TAK-593 also potently inhibits VEGF-induced tube formation of endothelial cells co-cultured with fibroblasts. Oral administration of TAK-593 exhibited strong anti-tumor effects against various human cancer xenografts along with good tolerability despite a low level of plasma exposure. Even after the blood and tissue concentrations of TAK-593 decreased below the detectable limit, a pharmacodynamic marker (phospho VEGFR2) was almost completely suppressed, indicating that its long duration of enzyme inhibition might contribute to the potent activity of TAK-593. Immunohistochemical staining indicated that TAK-593 showed anti-proliferative and pro-apoptotic effects on tumors along with a decrease of vessel density and inhibition of pericyte recruitment to microvessels in vivo. Furthermore, dynamic contrast-enhanced magnetic resonance imaging revealed that TAK-593 reduced tumor vessel permeability prior to the onset of anti-tumor activity. In conclusion, TAK-593 is an extremely potent VEGFR/PDGFR kinase inhibitor whose potent anti-angiogenic activity suggests therapeutic potential for the treatment of solid tumors.

A novel pyrrolo[3, 2-d]pyrimidine derivative, as a vascular endothelial growth factor receptor and platelet-derived growth factor receptor tyrosine kinase inhibitor, shows potent antitumor activity by suppression of tumor angiogenesis.

We recently reported that compound 20d (comp.20d), a novel pyrrolo[3, 2-d]pyrimidine derivative, is a potent and selective inhibitor of tumor angiogenesis-related kinases, including vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR). In this study, we show that comp.20d potently blocks the VEGF- and PDGF-stimulated cellular phosphorylation (IC(50) = 2.5 and 3.6 nM, respectively) and proliferation of HUVECs and human coronary artery smooth muscle cells with IC(50) values of 2.8 and 9.6 nM, respectively, and potently inhibits the VEGF-induced tube formation of endothelial cells cocultured with fibroblasts (IC(50) = 3.3 nM). Given orally twice daily, comp.20d at the doses of 1.5-6 mg/kg showed antitumor effects in mice bearing various human cancer xenografts. Consistent with the anti-angiogenic mechanism of action, histological examination of tumors from comp. 20d-treated mice indicated a decrease in microvessel density and inhibition of pericyte recruitment to microvessels, and these were concomitant with decreased interstitial fluid pressure that allowed for therapeutic intratumoral uptake of CPT-11 (irinotecan hydrochloride). In conclusion, comp.20d is an extremely potent inhibitor of VEGFR/PDGFR kinases whose activities suggest therapeutic potential for the treatment of solid tumors that rely on angiogenesis for their survival.

Prevention of bone loss in ovariectomized rats by pulsatile transdermal iontophoretic administration of human PTH(1-34).

Serum human parathyroid hormone (1-34)[hPTH(1-34)] levels and the anabolic effect of hPTH(1-34) were compared after administration using multiple pulses of iontophoresis or subcutaneous (sc) intermittent injections to ovariectomized (OVX) Sprague Dawley rats. Triple-pulse iontophoretic administration of hPTH(1-34) (doses: 40-400 microg/patch), achieved by repeated 30-min applications of a 0.1 mA/cm(2) current separated by 45-min rest intervals, produced three sharp peaks in the serum hPTH(1-34) level in response to application of the current. Each peak appeared at the end of the 30-min current application period and was proportional to the hPTH(1-34) dose. Compared with once-daily sc injections (7 pulses/week), triple-pulses iontophoretic administered 3 times/week (9 pulses/week) for 4 weeks produced dose-related increases in the bone mineral density (BMD) of the distal 1/3 femur. For the sc administration, the relative BMD values using the vehicle injection as a reference standard for 1, 5, and 25 microg/kg/day were 104, 114, and 121%, respectively. For iontophoretic administration, the relative BMD values using the placebo patch as a reference standard for 40, 120, and 400 microg/patch were 104, 110, and 116%, respectively. The increase in the BMD plotted against the area under the hPTH(1-34) serum level-time curve (AUC) over 1 week resulted in similar straight lines in the 9 pulses/week iontophoretic administration and the 7 pulses/week sc administration groups. The estimated iontophoretic dose giving an equivalent BMD to once-daily sc administration at 5 microg/kg/day was 120 microg/patch. These findings strongly suggest that three iontophoretic pulses administered on alternate days will exert an anabolic effect equivalent to that of daily sc administration at doses giving the same weekly AUC. Furthermore, this method of administering hPTH(1-34) might enable self-medication, a useful advance in the treatment of osteoporosis.