Development of Wireless Power-Transmission-Based Photodynamic Therapy for the Induction of Cell Death in Cancer Cells by Cyclometalated Iridium(III) Complexes.

Photodynamic therapy (PDT), a noninvasive method for cancer therapy, involves the generation of reactive oxygen species (ROS) by the photochemical excitation of photosensitizers (PSs) to induce cell death in cancer cells. A variety of PS including porphyrin derivatives and metal complexes such as iridium (Ir) complexes have been reported. In clinical trials, red-near infrared (NIR) light (650-900 nm) is preferred for the excitation of PSs due to its deeper penetration into tissues compared with visible light (400-500 nm). To overcome this limitation, we established a PDT system that uses cyclometalated iridium(III) (Ir(III)) complexes that are excited with blue light in the wireless power transmission (WPT) system. To achieve this, we developed a light-emitting diode (LED) light device equipped with a receiver coil that receives electricity from the transmitter coil through magnetic resonance coupling. The LEDs in the receiving device use blue light (470 nm) to irradiate a given Ir(III) complex and excite triplet oxygen (3O2) to singlet oxygen (1O2) which induces cell death in HeLa S3 cells (human cervical carcinoma cells). The results obtained in this study suggest that WPT-based PDT represents a potentially new method for the treatment of tumors by a non-battery LED, which are otherwise difficult to treat by previous PDT systems.

Intermittent local periodontal inflammation causes endothelial dysfunction of the systemic artery via increased levels of hydrogen peroxide concomitantly with overexpression of superoxide dismutase.

BACKGROUND: The present study was designed to examine whether the intermittent local periodontal inflammation induces endothelial dysfunction of the systemic artery caused by oxidative stress and if increased levels of hydrogen peroxide coexisted with overexpression of superoxide dismutase (SOD) as well as NADPH oxidase contribute to the oxidative stress. METHODS: The rats in lipopolysaccharides (LPS) group received 1500µg LPS injection to bilateral gingiva of the lower jaw a week interval from eight- to eleven-week-old. Isolated mandibles or aortas were subjected to the evaluation of histopathological changes, isometric force recordings, reactive oxygen species using 2',7'-dichlorofluorescin diacetate (10(-5)mol/L) and protein expression of NADPH oxidase subunits and SOD, respectively. RESULTS: Mandible sections demonstrated the periodontal inflammation only in the LPS group at three days, but not seven days, after the LSP injection. Acetylcholine (10(-9) to 10(-5)mol/L)-induced relaxation was reduced only in aortas from the LPS group. Gp91ds-tat and PEG-catalase restored the impaired dilation in arteries from the LPS group. Levels of reactive oxygen species were enhanced in aortas from the LPS group, whereas the increment was abolished by the treatment with gp91-ds-tat or PEG-catalase. Expression of a NADPH oxidase subunit p47phox and CuZn-SOD increased in the LPS group. CONCLUSIONS: The intermittent local periodontal inflammation induces systemic endothelial dysfunction caused by overproduction of reactive oxygen species in the systemic artery of rats and that overexpression of CuZn-SOD as well as a NADPH oxidase cytosolic subunit contributes to increased levels of hydrogen peroxide in blood vessels of this animal model.

High oxygen modifies vasodilator effect of cysteine via enhanced oxidative stress and thromboxane production in the rat mesenteric artery.

Whether high oxygen is harmful to the vascular function is unclear. The present study examined if high oxygen modifies vasodilator effect of cysteine via enhanced oxidative stress and thromboxane production. Rat mesenteric arteries with endothelium at 95 or 50 % oxygen were subjected to isometric force recordings, measurement of thromboxane B2 levels, determination of superoxide and peroxynitrite levels and evaluation of NADPH oxidase subunit protein expression, respectively. L-cysteine (0.01-3 mM) constricted or dilated arteries at 95 and 50 % oxygen, respectively. Thromboxane receptor antagonist SQ-29,548 (1 µM) abolished the constriction at 95 % oxygen. L-cysteine (3 mM) increased levels of thromboxane B2 in arteries upon 95 % oxygen application. L-cysteine relaxed arteries treated with superoxide inhibitor tiron (2 mM) or NADPH oxidase inhibitor gp91ds-tat (1 µM) irrespective of the oxygen concentration while ATP-sensitive K(+) channel inhibitor glibenclamide (1 µM) and cystathionine-γ-lyase (CSE) inhibitor DL-propargylglycine (10 mM) similarly abolished the relaxation. L-cysteine (3 mM) with 95 % oxygen augmented levels of superoxide as well as nitrotyrosine within the artery, concomitantly with enhanced membrane protein expression of NADPH oxidase subunit p47phox. The higher concentration of oxygen attenuates L-cysteine-induced vasodilation via superoxide production mediated by NADPH oxidase along with thromboxane A2 production, resulting in vasoconstriction. The increased levels of superoxide, as well as peroxynitrite, coexist with the impaired vasodilation related to ATP-sensitive K(+) channels and CSE. Higher oxygen with plasma cysteine may cause oxidative stress and vasoconstrictor prostanoid production in blood vessels.

Effectiveness of methods for detaching orthodontic implants likely to fracture upon rotational torque - an animal study.

Orthodontic implants may fracture at the cortical bone level upon rotational torque. The impacted fragment can be detached by a range of methods, which are all more or less time-consuming and injurious to the cortical bone. The aim of this study was to compare three different methods for detaching an orthodontic implant impacted in cortical bone. Health Sciences University of Hokkaido animal ethics committee approved the study protocol. Orthodontic titanium-alloy (Ti-6Al-4 V) implants were placed bilaterally on the buccal side of the mandible of beagle dogs. Subsequently, the implants were detached using either a low-speed handpiece with a round bur, alternatively by use of a low-power or a high-power ultrasonic instrument. In the first experiment, 56 orthodontic implants were placed into the dissected mandible from 7 animals. The methods for detachment were compared with respect to time interval, as well as associated undesirable bone loss as appraised by use of cone-beam computed tomography. In experiment two, 2x2 implants were placed bilaterally in the mandible of 8 animals and subsequently detached by manual rotational torque, and the described three methods for detachment. The implant socket was investigated histologically as a function of removal method immediately after removal, and after 1, 3 and 8 weeks and contrasted with the healing of the socket of the implant that was detached by manual rotational torque. Statistical significance was appraised by the use of non-parametric Kruskal-Wallis one-way analysis of variance. The method using the low-power ultrasonic required significantly longer removal time versus the two other methods, i.e. high-power ultrasonic and low-speed handpiece with a round bur (p < 0.02). The amount of undesirable bone loss was substantially larger with low-speed handpiece with a round bur compared to the two ultrasonic methods (p < 0.05). Bone formation after 3 weeks of healing was more complete following the use of low or high-power ultrasonic instrument in comparison with a low-speed handpiece rotary instrument method. Orthodontic implants likely to fracture upon rotational torque or impacted fractured fragments should be detached preferably with an ultrasonic instrument, because of less associated bone loss and more rapid bone healing compared to the use of a low-speed handpiece rotary instrument.

Kynurenine causes vasodilation and hypotension induced by activation of KCNQ-encoded voltage-dependent K(+) channels.

Kynurenine is a potential contributor to hypotension in animal and human sepsis. The present study was designed to examine whether the voltage-dependent K(+) channels encoded by the KCNQ gene family (Kv7 channels) mediate vasodilator effects of kynurenine and whether modulation of these channels ameliorates hypotension caused by this compound. Rat aortas and mesenteric arteries or human omental arteries without endothelium were used. Some rings were incubated with the selective Kv7 channel inhibitor linopirdine (10 µM). l-Kynurenine (10 µM-1 mM) induced concentration-dependent relaxation in rat aortas and mesenteric arteries as well as human omental arteries, whereas linopirdine abolished the relaxation. l-Kynurenine (1 mM) produced hyperpolarization of vascular smooth muscle, which was reversed by linopirdine (10 µM). Wistar rats received l-kynurenine (1 mM) iv and subsequent linopirdine (10 µM) iv under 3% sevoflurane inhalation. l-Kynurenine iv caused hypotension, whereas linopirdine iv partially reversed it. In conclusion, kynurenine dilates arteries from rats as well as humans via Kv7 channels in the vascular smooth muscle. In rats, this tryptophan metabolite causes hypotension, which is partly counteracted by Kv7 channel inhibition. These results suggest that modulation of Kv7 channels may be a novel strategy to treat hypotension induced by the kynurenine.

In vivo degradation of orthodontic miniscrew implants: surface analysis of as-received and retrieved specimens.

This study investigated in vivo degradation of Ti-6Al-4V alloy miniscrew implants. Miniscrew implants were placed in patients, and the surfaces were studied upon retrieval by scanning electron microscopy, microscale X-ray photoelectron spectroscopy, elastic recoil detection analysis and nanoindentation testing. Bone-like structures were formed on the retrieved specimens. The hardness and elastic modulus of the surfaces of the retrieved specimens were significantly lower than the as-received specimens, although no statistically significant differences were observed for the hardness and elastic modulus in the bulk region. Thick organic over-layer containing carbon, oxygen, and nitrogen, with the thickness greater than 50 nm, covered the retrieved specimens, and higher concentrations of hydrogen were detected in the retrieved specimens compared with the as-received specimens. Minimal degradation of the bulk mechanical properties of miniscrew implants was observed after clinical use, although precipitation of bone-like structures, formation of a carbonaceous contamination layer, and hydrogen absorption were observed on the surfaces of miniscrew implants.

Micro-CT and histologic analyses of bone surrounding immediately loaded miniscrew implants: comparing compression and tension loading.

This study investigated the effect of immediate force on bone adaptations surrounding miniscrew implants. Ten miniscrew implants were placed on the mandibles in three beagle dogs. Five pairs of miniscrew implants were immediately loaded with 150 g of continuous force using nickel-titanium coil springs for 8 weeks. The values of bone mineral density (BMD), bone mineral content (BMC), and bone volume (BV) of cortical and trabecular bone for compression loading and tension loading were obtained by µCT analysis. The percentages of bone-to-implant contact (BIC) in the compression and tension regions for cortical and trabecular bone were obtained by histologic analysis. The BMD values for the compression region of cortical bone were significantly higher compared to the tension region. The BIC values in cortical and trabecular bone at tension and compression regions were similar. In conclusion, immediate loading does not inhibit osseointegration of miniscrew implants but may stimulate bone mineralization.

Effect of immediate loading on the biomechanical properties of bone surrounding the miniscrew implants.

The aim of this study was to investigate the effect of immediate loading on the biomechanical properties of bone surrounding a miniscrew implant. Forty titanium alloy miniscrew implants were placed on the buccal side of the maxillae and mandibles in four beagle dogs. Twelve pairs of miniscrew implants were immediately loaded with approximately 150 g of continuous force using nickel-titanium coil springs and the remaining 16 implants were left unloaded for 8 weeks. Nanoindentation testing was performed (peak load 10 mN) and the hardness and elastic modulus were calculated. Two series of indentations (in cortical and trabecular bone) for both the compression and tension sides were made. For each site, five indentations were placed approximately 25 µm from the implant-bone interface and 250 µm from the screw thread. The mean hardness and elastic modulus were generally higher in mandibles than maxillae and were higher in cortical bone than in trabecular bone. The trabecular bone near the implant-bone interface on the compression side was significantly harder than that at other locations in trabecular bone. In conclusion, this is the first study that has investigated the biomechanical properties of bone surrounding a miniscrew implant under immediate loading using nanoindentation testing. The mechanical properties of bone surrounding a miniscrew implant may be influenced by immediate loading.

Effect of the quantity and quality of cortical bone on the failure force of a miniscrew implant.

This study examined the influence of the quantity and quality of cortical bone on the failure force of miniscrew implants. Twenty-six titanium alloy miniscrew implants (AbsoAnchor) 1.4mm in diameter and 5 or 7 mm long were placed in cross-sectioned maxillae (n = 6) and mandibles (n = 20) of human cadavers. Computed tomography imaging was used to estimate the cortical bone thickness and bone mineral density [total bone mineral density (TBMD, values obtained from cortical bone plus trabecular bone); cortical bone mineral density (CBMD, values obtained from only cortical bone)]. Maximum force at failure was measured in a shear test. Nanoindentation tests were performed to measure the hardness and elastic modulus of cortical bone around the miniscrew implants. The mean failure force of miniscrew implants placed in mandibles was significantly greater than that for implants in maxillae, and the bone hardness of mandibles was significantly greater than that of maxillae. The length of miniscrew implants did not influence the mean failure force in monocortical placement in the mandible. Cortical bone thickness, TBMD, CBMD, and bone hardness were significantly related to the mean failure force. CBMD was related to the mechanical properties of cortical bone. In conclusion, the quantity and quality of cortical bone greatly influenced the failure force of miniscrew implants.

Effects of CO(2) laser debonding of a ceramic bracket on the mechanical properties of enamel.

OBJECTIVE: To investigate the effects of CO(2) laser debonding of a ceramic bracket on the mechanical properties of tooth enamel. MATERIALS AND METHODS: Fifty-three human premolars were used in this study. The temperature changes of cross-sectioned specimens during laser irradiation were monitored with an infrared thermographic microscope system. Different laser output settings (3, 4, 5, and 6 W) were compared. The shear bond strength of brackets after laser irradiation was measured for specimens bonded with a conventional etch and rinse adhesive or with a self-etching adhesive, and the adhesive remnant index score was calculated. The hardness and elastic modulus of cross-sectioned enamel after laser irradiation were investigated by the nanoindentation test. Data were compared by one-way and two-way analysis of variance, followed by the Scheffé test. RESULTS: The temperature of enamel increased by about 200 degrees C under CO(2) laser irradiation with a relatively high output (5 and 6 W), and a temperature increase of about 100 degrees C to 150 degrees C was seen under laser irradiation with a low output (3 and 4 W). The bracket shear bond strength decreased under all laser irradiation conditions. The hardness and elastic modulus of enamel were not affected by CO(2) laser debonding. CONCLUSION: CO(2) laser debonding may not cause iatrogenic damage to enamel.

Force and amount of resin composite paste used in direct and indirect bonding.

OBJECTIVE: To investigate the relationship between the forces applied by the operator and the amount of adhesive used in the direct and indirect bonding methods. MATERIALS AND METHODS: A system for measuring the force applied by operator was used to test specimens prepared by 12 orthodontic specialists. To determine the proper amount of adhesive, metal brackets were bonded to transparent resin teeth using composite resin paste and different forces (100, 200, and 300 g); the area of the composite resin paste was then measured using image-analysis software. The mean forces applied in direct and indirect bonding were compared by Student's t-test. RESULTS: Various values for force were obtained for the direct bonding (53-940 g) and indirect bonding (150-870 g) techniques. Although in all cases the area of composite resin paste after the application of constant force was greater than the area of the metal brackets, an insufficient amount of composite resin paste on the bracket base was observed with forces of 100 and 200 g. CONCLUSIONS: A force of greater than 200 g might be preferable for obtaining a thin composite resin layer and for achieving sufficient spreading of the composite resin paste.

A mini-implant for orthodontic anchorage in a deep overbite case.

This article describes the orthodontic treatment of a 19-year-old female patient with anterior crowding. There was a moderate arch length discrepancy in the lower dental arch, a significant deep overbite, and a "gummy smile." We inserted an orthodontic mini-implant as anchorage for the intrusion of the upper incisor segment, followed by alignment of the upper and lower dental arches with an edgewise appliance without tooth extraction. The overbite was corrected from +7.2 mm to +1.7 mm by upper incisor intrusion, and the gummy smile was improved. Good occlusion and facial esthetics were achieved, and these results have been maintained for two years after completion of the active treatment.

Improvement in smoothness of the chewing cycle following treatment of anterior crossbite malocclusion: a case report.

This is a report of a case in which improvement in masticatory jaw movement kinematics occurred following orthodontic treatment. A patient who demonstrated a skeletal Class II jaw relationship, with anterior crossbite between the right upper and lower lateral incisors, underwent treatment with an edgewise appliance. The trajectories and smoothness of the patient's jaw-closing movement were compared before and after orthodontic treatment. The correction of the anterior crossbite allowed the patient to consistently close the jaw with wider lateral excursion. Furthermore, after treatment, smoothness of the jaw-closing movements increased significantly, and the velocity profile was characterized as closer to that predicted by the minimum jerk (maximum smoothness) kinematic model. These findings suggest the value of trajectory smoothness (jerk-cost) as an objective indicator of kinematic improvement in gum chewing. In addition, the correction of anterior crossbite is demonstrated to enable the patient to perform smoother jaw-closing movements during chewing.

Report of a patient with hypoglossia-hypodactylia syndrome and a review of the literature.

OBJECTIVE: To present the morphology of the extremities, craniofacial structures, and the oral cavity based on roentgencephalometry and three-dimensional computed tomography and magnetic resonance imaging scanning in a patient with hypoglossia-hypodactylia syndrome, discuss the orthodontic treatment method, and review the literature for the syndrome. PATIENT: The patient was a 6-year-old boy diagnosed with hypoglossia-hypodactylia syndrome at birth. He had hypodactylia as well as micrognathia with steep inclination of the anterior surface of the mandible in relation to the lower mandibular plane. He had missing mandibular incisors with concomitant bone defect limited to the associated alveolar ridge and an absence of any malformations in the mandibular ramus and condylar head. The patient had a bilateral scissors bite with an extremely constricted mandibular dental arch, skeletal Class II jaw relationship with an average mandibular plane angle and maxillary incisors inclined palatally. He had extremely reduced tongue size and hypertrophy of the floor of the mouth. Anomalies of the central nervous system were not observed. There was no evidence of hearing loss.

Rigid external distraction osteogenesis for a patient with maxillary hypoplasia and oligodontia.

OBJECTIVE: In this report, the orthodontic treatment combined with rigid external distraction osteogenesis in a 5.5-year-old girl with midfacial hypoplasia and oligodontia is described. PATIENT: The child presented with a reduced maxilla, protruding lower lip, skeletal Class III jaw relationship with a low mandibular plane angle, a short and flattened nose, anterior crossbite, and aplasia of 16 permanent teeth. The patient was treated with rigid external maxillary distraction osteogenesis, maxillary protraction headgear, and Class III elastics. Following treatment, the maxilla was displaced in a forward direction with new bone formation at the tuberosities and the mandible rotated backward in relation to the anterior cranial base. The anterior crossbite was corrected, and the skeletal jaw relationship changed from a Class III to a Class I skeletal pattern. The soft tissue facial profile showed that the nasal projection had been increased, the nasolabial angle increased, and the lower lip protrusion was reduced. Postoperative treatment results were acceptable. CONCLUSION: This report documents that early maxillary advancement with rigid external osteogenesis offers a promising treatment alternative for a very young patient with maxillary hypoplasia and oligodontia.

Numerical simulations of bubble motion in a vibrated cell under microgravity using level set and VOF algorithms.

Understanding the stability of fluid interfaces subjected to small vibrations under microgravity conditions is important for designing future materials science experiments to be conducted aboard orbiting spacecraft. During the STS-85 mission, experiments investigating the motion of a large bubble resulting from small, controlled vibrations were performed aboard the Space Shuttle Discovery. To better understand the experimental results, two-and three-dimensional simulations of the experiment were performed using level set and volume-of-fluid interface tracking algorithms. The simulations proved capable of predicting accurately the experimentally determined bubble translation behavior. Linear dependence of the bubble translation amplitude on the container translation amplitude was confirmed. In addition, the simulation model was used to confirm predictions of a theoretical inviscid model of bubble motion developed in a previous study.

Facial asymmetry in subjects with skeletal Class III deformity.

We investigated the frequency, site, amount, and direction of facial asymmetry in human adults with mandibular prognathism and examined if these characteristics were associated postnatally with cardinal clinical signs that may indicate a predisposition to facial asymmetry. Two hundred twenty young Japanese adults (69 men and 151 women) who exhibited skeletal Class III malocclusions were selected. The sample was divided into a Postnatal Factor Group and a Nonpostnatal Factor Group. The former group included those who had: (1) received orthodontic treatment using a chin cap; (2) exhibited clinical symptoms of temporomandibular joint (TMJ) disorder; (3) reported a history of maxillofacial trauma; or (4) radiographic abnormality of the condyles. Subjects with a deviation of more than 2 mm from the facial midline associated with any of the 4 landmarks (ANS, U1, L1 and Me) were classified as asymmetric and the asymmetry was measured on a postero-anterior (P-A) cephalogram. Radiographic facial asymmetry was found frequently (70%-85%, for Menton), and most obviously in the lower jaw (P < .05). Lateral displacement toward the left side of the face occurred more often than right-sided deviation (P < .001, for Menton). However, the Postnatal Factor Group showed a higher proportion of subjects with lateral deviation toward the right side (P = .0031) and a greater amount (P < .0001) of chin deviation. This was due to the fact that the subjects having TMJ problems as a postnatal factor showed no directional uniqueness in jaw deviation and exhibited a longer distance of deviation.

A stent fabricated on a selectively colored stereolithographic model for placement of orthodontic mini-implants.

The purpose of this report is to present a new method for placing orthodontic mini-implants using a stent fabricated on a selectively colored stereolithographic model. A stent was fabricated that incorporated a guide groove drilled in accordance with the planned direction of the mini-implant. Tooth crowns, gingiva, tooth roots, and the maxillary sinuses were clearly identified in the stereolithographic model. As a result, the stent could be fabricated while taking into account the anatomic characteristics of both the bone interior and the dental surface. A stent fabricated on the selectively colored stereolithographic model is suggested to be a promising device for guiding placement of orthodontic mini-implants adjacent to the tooth roots and the maxillary sinuses.