Noncontact Tactile Display Based on Radiation Pressure of Airborne Ultrasound.

This paper describes a tactile display which provides unrestricted tactile feedback in air without any mechanical contact. It controls ultrasound and produces a stress field in a 3D space. The principle is based on a nonlinear phenomenon of ultrasound: Acoustic radiation pressure. The fabricated prototype consists of 324 airborne ultrasound transducers, and the phase and intensity of each transducer are controlled individually to generate a focal point. The DC output force at the focal point is 16 mN and the diameter of the focal point is 20 mm. The prototype produces vibrations up to 1 kHz. An interaction system including the prototype is also introduced, which enables users to see and touch virtual objects.

Frequency of nocturnal sudden death in patients with multiple system atrophy.

Sudden death has been reported in patients with multiple system atrophy (MSA), although the frequency of this event has not been well delineated. We investigated the frequency and potential causes of sudden death in patients with MSA. During the 5-year observation period, 10 of 45 patients with probable MSA died. The causes of death included sudden death of unknown etiology (seven patients), aspiration pneumonia (one patient), asphyxia after vomiting (one patient), and lung cancer (one patient). The mean survival time of patients with sudden death was 63.0 +/- 24.7 months (range, 39-116 months). Among seven patients who experienced sudden death, six were found to have died during sleep. Among these patients, two had been treated with tracheostomy and three with continuous positive airway pressure (CPAP) or noninvasive positive pressure ventilation (NPPV) during sleep, suggesting that these treatments do not always prevent sudden death in patients with MSA. Nocturnal sudden death should be recognized as the most common mechanism of death in patients with MSA.

Clodronate inhibits PGE(2) production in compressed periodontal ligament cells.

Periodontal ligament (PDL) cells play an essential role in orthodontic tooth movement. We recently reported that clodronate, a non-N-containing bisphosphonate, strongly inhibited tooth movement in rats, and thus could be a useful adjunct for orthodontic treatment. However, it is not clear how clodronate affects the responses of PDL cells to orthodontic force. In this study, we hypothesized that clodronate prevents the mechanical stress-induced production of prostaglandin E(2) (PGE(2)), interleukin-1beta (IL-1beta), and nitric oxide (NO) in human PDL cells. A compressive stimulus caused a striking increase in PGE(2) production, while the responses of IL-1beta and NO were less marked. Clodronate concentration-dependently inhibited the stress-induced production of PGE(2). Clodronate also strongly inhibited stress-induced gene expression for COX-2 and RANKL. These results suggest that the inhibitory effects of clodronate on tooth movement and osteoclasts may be due, at least in part, to the inhibition of COX-2-dependent PGE(2) production and RANKL expression in PDL cells.

Circadian rhythms in serum bone markers and their relation to the effect of etidronate in rats.

Circadian rhythmicity is an essential feature of bone metabolism. The present study was undertaken to (Aoshima et al., 1998) determine the changes in bone resorption and formation in rats over 24h, (Black et al., 1999) evaluate the effect of the consecutive administration of etidronate on circadian rhythms of serum bone markers, and (Blumsohn et al., 1994) determine whether the effect of etidronate on bone metabolism is circadian time-dependent. One hundred twenty male Wistar rats, which had been adapted to a 12/12h light/dark cycle, were injected subcutaneously once daily with either 0.5 mgP/kg etidronate or 0.9% NaCl (control group) at 0090, 1300, 1700, 2100, 0100, or 0500h for 10d. Serum was collected and tibiae were dissected 24h after the last injection. Serum pyridinoline (Pyd), tartrate-resistant acid phosphatase (TRAP), osteocalcin (OC), alkaline phosphatase (ALP), calcium (Ca), phosphorus (Pi), calcitonin (CT), and parathyroid hormone (PTH) were determined. Bone mineral density (BMD) in the proximal tibia, and the rate of formation of longitudinal trabecular bone over the past 48h were also determined using a chronological labeling method with NTA-Pb. The results showed characteristic circadian rhythms in serum bone markers in rats, with peaks in both bone resorption and bone formation during the animals' rest span. The administration of etidronate at the different times of the day decreased the level of bone-resorption markers (Pyd and TRAP) without affecting the circadian patterns of markers of bone formation (OC and ALP). However, the magnitude of the decrease due to etidronate was not uniform throughout the day, and was greatest during the daytime. Etidronate increased the BMD in the tibial metaphysis in all of the time-treatment groups, but the magnitude of the increase did not vary with the time of etidronate administration. The present data provide a physiological basis for future studies on bone metabolism and may be important in the design of future experiments and in the interpretation of experimental data.

Diurnal variation in the response of the mandible to orthopedic force.

Bone and cartilage metabolism is known to be more active during rest than during periods of activity. The purpose of this study was to examine the hypothesis that mandibular retractive force could be more effective when applied to rats during rest. Mandibular retractive force caused a considerable reduction in the condylar length in experimental groups, and the magnitude of this reduction was greater in the Light-period (08:00-20:00) group than in the Dark-period (20:00-08:00) group. The differentiation and proliferation of chondrocytes were inhibited in animals in the Light-period group, compared with those in the Dark-period group. These results suggest that the orthopedic effects of mandibular retractive force vary depending on the time of day the force is applied, and that such force may be more effective while animals are resting than while they are active.

Estrous-cycle-dependent variation in orthodontic tooth movement.

Sex hormones, including estradiol, play important physiological roles in bone metabolism. The purpose of this study was to investigate whether there is estrous-cycle-dependent variation in orthodontic tooth movement, and, if so, to determine the mechanism. Ten-week-old female Wistar rats were used. They received repeated orthodontic force during specific phases in the estrous cycle. Tooth movement in animals that received force principally in estrus was about 33% greater than that in animals that received such force principally in pro-estrus (p < 0.05). Serum estradiol levels also varied according to the estrous cycle, with a peak during pro-estrus and a nadir during estrus, and were inversely related to tooth movement. Furthermore, there were negative correlations between estradiol and both serum TRAP activity and pyridinoline (r = -0.42, p < 0.05; r = -0.59, p < 0.001). These results suggest that cyclic changes in the estradiol level may be associated with the estrous-cycle-dependent variation in tooth movement through its effects on bone resorption.

Activin A increases the bone mass of grafted bone in C3H/HeJ mice.

Activin A, a member of the TGF-b superfamily, is abundant in bone matrix, but little is known about its physiological role in bone metabolism. The present study was undertaken to determine whether topical activin A can increase the bone mass of isografted bone. The tibiae were bilaterally dissected from a donor C3H/HeJ mouse and transplanted subcutaneously in the dorsal region of a recipient mouse. One isografted tibia was topically infused for either 1, 2, 3, or 4 weeks with activin A, using an osmotic minipump at a dose of 0.02, 0.2, or 2 ng/hr. The other tibia was infused with 0.9% NaCl (control). The following results were obtained: (1) Topical activin A (2 ng/hr) stimulated periosteal bone formation after 2 or 3 weeks. The bone area in a standardized transverse section averaged 1.3 fold that in the control. (2) Numerous cuboidal or conical osteoblasts appeared on the surface of newly formed bone after the infusion of activin A for 2 or 3 weeks. Autoradiographic studies using 3H-proline revealed that the surface area of newly formed bone labelled with autoradiographic silver grains was greater in activin A-treated bone than in the control, suggesting an increased synthesis and secretion of collagen by osteoblasts. (3) Topical activin A increased the number of osteoclasts after 2 to 4 weeks. Furthermore, enhanced or increased bone resorption was observed in the projected anterior site of activin A-treated bone after 4 weeks. These results suggest that topical activin A increases the bone mass of isografted bone by increasing bone turnover.

Effects of topical administration of clodronate on alveolar bone resorption in rats with experimental periodontitis.

BACKGROUND: We examined whether topical administration of a bisphosphonate clodronate could prevent alveolar bone loss in rats with experimental periodontitis. METHODS: On day 0, elastic rings were placed around the cervix of the right and left maxillary first molars (M1) to induce inflammatory periodontitis. Fifty microl of clodronate solution at a concentration of either 0 (0.9% NaCl), 20, 40, or 60 mM was injected into the subperiosteal palatal area adjacent to the interdental area between M1 and M2 on either the left or right (experimental) side on days 0, 2, 4, and 6. The contralateral side served as a control and received 0.9% NaCl solution without clodronate. The animals were sacrificed on day 7. RESULTS: Histological examination and determination of bone mineral density in the interdental alveolar bone area between M1 and M2 revealed that placement of an elastic ring caused severe vertical and horizontal bone resorption on the control side, while the topical administration of clodronate significantly prevented such alveolar bone loss. The number of osteoclasts on the experimental side was decreased compared with the control side. Furthermore, many of the osteoclasts on the experimental side were detached from the surface of the alveolar bone and had degenerated appearances, such as rounded shapes and a loss of polarity. CONCLUSIONS: These results suggest that topical administration of clodronate may be effective in preventing osteoclastic bone resorption in periodontitis.

Radiotherapy with concurrent docetaxel and carboplatin for head and neck cancer.

BACKGROUND: This study was designed to evaluate the concomitant use of docetaxel and carboplatin for radiosensitization in head and neck cancer. MATERIALS AND METHODS: One dose of docetaxel at 10 mg/m2 and five doses of carboplatin at AUC of 0.4 per week were administered to patients during the first two weeks of radiotherapy. Sixteen patients were treated with this regimen. Radiotherapy was given to a total dose of 64.8 to 82.0 Gy. Altered fractionation radiotherapy was performed in 12 patients with untreated advanced tumors. RESULTS: The complete response (CR) rate was 81%, with a partial response (PR) rate of 19%. Toxicities included grade 3 mucositis in 69% of patients and grade 2 dermatitis in 56% of patients. CONCLUSION: This schedule of docetaxel and carboplatin combined with radiotherapy may become a useful approach for the management of head and neck cancer with proper management of mucositis.

Influence of nocturnal bruxism on the stomatognathic system. Part I: a new device for measuring mandibular movements during sleep.

The purpose of this study was to investigate the influence of bruxism on the stomatognathic system. A new device for measuring nocturnal mandibular movements was developed using a PIN photodiode sensor, integrated with polysomnography including electromyography (EMG), electroencephalography (EEG) and electro oculography (EOG). One bruxing event was defined depending upon EMG activities above 5% maximum voluntary contraction (MVC), and mandibular movement for each event was classified into three patterns (clenching, grinding and mix). Three subjects were selected for this study. Two of these reported a bruxing habit and one subject had some symptoms of temporomandibular dysfunction (TMD). Mandibular movement was analysed for these subjects. Frequency and duration of the bruxism events were 4.5-10.9 and 47.8-174.9 s h(-1) respectively. Clenching type bruxism was most frequently observed for all three subjects and EMG activities during clenching were stronger than grinding.

What controls attention in natural environments?

The highly task-specific fixation patterns revealed in performance of natural tasks demonstrate the fundamentally active nature of vision, and suggest that in many situations, top-down processes may be a major factor in the acquisition of visual information. Understanding how a top-down visual system could function requires understanding the mechanisms that control the initiation of the different task-specific computations at the appropriate time. This is particularly difficult in dynamic environments, like driving, where many aspects of the visual input may be unpredictable. We therefore examined drivers' abilities to detect Stop signs in a virtual environment when the signs were visible for restricted periods of time. Detection performance is heavily modulated both by the instructions and the local visual context. This suggests that visibility of the signs requires active search, and that the frequency of this search is influenced by learnt knowledge of the probabilistic structure of the environment.

Phenytoin-induced bone loss and its prevention with alfacalcidol or calcitriol in growing rats.

Studies were carried out to determine the effects and mechanism of action of phenytoin on the bone metabolism in male rats. Administration of phenytoin, 20 mg/kg/ day for 5 weeks, did not affect the growth curve. Biochemical data indicated that the serum osteocalcin, a marker of bone formation, was decreased significantly but there were no significant differences in the levels of serum calcium, pyridinoline, 25-hydroxyvitamin D3 (25OHD) and parathyroid hormone (PTH) in the phenytoin-treated group compared with the vehicle-treated group. The values of bone mineral density (BMD) were decreased in all regions of bones tested (mandibular head, tibial metaphysis, tibial diaphysis, femoral metaphysis, and femoral diaphysis) in the phenytoin-treated group. In histomorphometric analysis, phenytoin decreased trabecular bone volume and trabecular thickness, and increased osteoclast numbers per area of bone surface in the secondary trabecular bone of the tibia. Additionally, there was no significant difference in osteoid thickness. Combined administration of either alfacalcidol or calcitriol with phenytoin for 5 weeks prevented the reduction of BMD induced by phenytoin. From these findings, it is unlikely that toxic effects on the growth curve caused the decreased BMD induced by phenytoin. It is also evident that repeated administration of phenytoin may cause osteopenia which may be due to bone loss by inhibiting bone formation and/or by accelerating bone resorption rather than osteoid accumulation. The bone loss is not rachitic because of the lack of increase in osteoid thickness. Moreover, combined administration of alfacalcidol or calcitriol with phenytoin showed a preventative effect against bone loss. The bone loss induced by phenytoin in this study may be a convenient model for further research into the problem of drug-induced osteopenia.

Tooth movement and changes in periodontal tissue in response to orthodontic force in rats vary depending on the time of day the force is applied.

The purpose of this study was to investigate whether there are any differences in tooth movement or in the response of periodontal tissue to orthodontic force when the force is applied at different times of the day. One hundred 6-week-old male Wistar rats were divided into one control group without force application and three experimental groups based on the time of day the force was applied to the upper first molars. Animals in the whole-day group received force continuously throughout the experimental period, while animals in the light- and dark-period groups received force only during the light (07:00-19:00) or dark period (19:00-07:00), respectively. Tooth movement was measured using the occlusal view of a precise plaster model with a profile projector. Periodontal tissues were evaluated histologically. The time course of tooth movement varied among the groups. Tooth movement over 21 days in the whole-day and light-period groups was about twice that as in the dark-period group. The formation of new bone on the tension side in the whole-day and light-period groups was more than twice that as in the dark-period group. On the pressure side, more osteoclasts appeared on the alveolar bone in the whole-day and light-period groups than in the dark-period group. The light-period group showed less extensive hyalinization of the periodontal ligament (PDL) than the whole-day group. The area of root resorption on day 21 also varied among the groups. Interference by masticatory forces did not seem to be a principal cause of the decreased tooth movement in the dark-period group. These results indicate that there are considerable variations in tooth movement and in the response of periodontal tissue to orthodontic force when the force is applied at different times of the day in rats. The results suggest that diurnal rhythms in bone metabolism have important implications in orthodontic treatment.

Ultrasonic six-axis deformation sensing.

In this paper, we describe a newly developed deformation sensing scheme in a soft medium, which is based on precise encoding and decoding of deformation components into ultrasound wavefronts. It can detect three translational components and three rotational components of displacement around a transmitter position nearly simultaneously. We assume a cell structure that consists of a 2 x 2 ultrasonic transmitter matrix and a 2 x 2 ultrasonic receiver matrix, which are placed face to face at a distance of a few tens of wavelengths. All of the transmitter elements are driven sinusoidally and simultaneously, but they are switched into the same, reversed, or quadrature phases to generate a particular shape of wavefront on the receiver matrix. The receiver elements are connected in such a way to obtain amplitude and spatial gradients of the wavefront at a center of the receiver matrix. First, we describe the transduction theory for the six dimensions and show the orthogonality, locality, and simultaneity of this sensing scheme. Then, we describe the fabrication and experimental evaluation of the cell. We also describe a prototype tactile sensor in which a single cell is embedded in a flexible hemispherical fingertip-like body.

Effect of suprachiasmatic nucleus lesion on circadian dentin increment in rats.

Mammalian dentin universally shows circadian increments. However, little is known about the mechanism of this phenomenon. The purpose of the present study was to investigate the role of the suprachiasmatic nucleus (SCN) in the generation of circadian rhythm in dentin increment. Rats underwent lesion of the SCN by electrodes and were maintained under constant light to examine whether the circadian increment free runs. The rats were injected with nitrilotriacetato lead to chronologically label the growing dentin. Two weeks after the operation, maxillary incisors and the locations of lesions in the brain were examined histologically. A harmonic (Fourier) analysis was performed to examine the densitometric pattern of the dentin increments to determine their periodicity. In rats with a completely lesioned SCN, ultradian increments, but no circadian increments, were observed in the dentin. Alternatively, in rats with an intact or only partially lesioned SCN, circadian increments persisted or were only temporarily disturbed. These results suggest that the SCN plays an important role in the generation of the circadian dentin increment in rats.

Preventive effects of a Chinese herbal medicine, hochu-ekki-to, on bone loss in ovariectomized rats.

To evaluate the effects of a traditional Chinese herbal medicine, Hochu-ekki-to [Bu-zong-yi-qi-tang], on the bone loss induced by ovariectomy in rats, ovariectomized female rats of the Sprague-Dawley strain at age 35 weeks were daily given Hochu-ekki-to and/or 17 alpha-ethynylestradiol for 8 weeks by gastric tube and, subsequently, the serum hormone levels and the tibial bone mineral density were measured. Hochu-ekki-to treatment suppressed the ovariectomy-induced reduction of the bone mineral density in the whole and metaphysis of tibia with a slight increase of serum levels of estradiol and progesterone, maintaining bone mineral density values similar to that in the estradiol treated ovariectomized rats, as well as the intact control rats. Hochu-ekki-to is suggested to elevate the serum levels of ovarian hormones slightly and prevent bone loss in ovariectomized rats.

Novel method for simultaneous analysis of p53 and K-ras mutations and p53 protein expression in single histologic sections.

BACKGROUND AND OBJECTIVE: Abnormal protein expression and gene mutation should be examined on exactly identified lesions. To perform simultaneous analyses of oncogene or tumor suppressor gene mutations and related protein expression in single histologic sections, we have developed a novel method using an antigen-retrieval solution for a polymerase chain reaction template before immunohistochemical staining. METHODS: Using 20 cases of sporadic colorectal carcinoma, several kinds of antigen-retrieval solutions were tested after heating rehydrated, 4-microm-thick, formalin-fixed, paraffin-embedded histologic sections at 96 degrees C for 20 minutes. Polymerase chain reaction-single-strand conformation polymorphism analysis was conducted for p53 (exons 5 through 9) and K-ras (exons 1 and 2), and the histologic sections were then immunostained with monoclonal antibody against p53. RESULTS: DNA analysis of antigen-retrieval solutions was possible in all 20 cases and revealed completely consistent results (100%) with fresh cancer tissue and microdissected cancer tissue of paraffin-embedded histologic sections. With this method, K-ras mutations were positive in 10 of 20 cases (exon 1 in 9 cases and exon 2 in 1 case) and p53 mutations were positive in 9 of 20 cases (exon 5 in 4 cases, exon 6 in 1, exon 7 in 3, and exon 8 in 1 case), with 8 of the 9 p53 mutation cases showing diffuse p53 protein expression on immunostaining. Base alterations of all abnormal conformers were confirmed with direct sequencing. For polymerase chain reaction-single-strand conformation polymorphism analysis, sodium citrate buffer (pH 6.0) was found to be the optimal antigen-retrieval solution. CONCLUSIONS: This newly developed method can be used for routine immunostaining and genetic analysis with single histologic sections.

Antinociceptive effect induced by intraperitoneal administration of vitamin K2 (menatetrenone) in ICR mice.

The antinociceptive effect of vitamin K2 (menatetrenone) in mice was examined using tail-flick and formalin test. Menatetrenone at doses of 10, 50 and 100 mg/kg, i.p. produced a dose-dependent and significant inhibition of the tail-flick response in mice. Menatetrenone (50 and 100 mg/kg, i.p.) had no significant effect on the duration of the first phase of the formalin-induced flinching. However, menatetrenone (100 mg/kg, i.p.) significantly inhibited the second phase of the formalin-induced flinching. I.p. administration of menatetrenone (100 mg/kg) significantly reduced the duration of nociceptive responses induced by i.t. injection of bradykinin, but not of substance P, prostaglandin E2 or N-methyl-D-aspartate (NMDA). These present data suggest that i.p. pretreatment with menatetrenone produced dose-dependent antinociceptive effect in mice. This effect may be, at least in part, mediated by the inhibition of bradykinin dependent nociceptive transmission in the spinal cord.

Bone mineral density of alveolar bone in rats during pregnancy and lactation.

BACKGROUND: The present study was designed to investigate the effect of pregnancy and lactation on the bone mineral density (BMD) of alveolar bone in rats fed diets containing different amounts of calcium (Ca). The effects of different levels of Ca intake by the mothers on the BMD of alveolar bone in their pups were also examined. METHODS: Ten-week-old female Wistar rats were housed with male rats for breeding and were divided into 3 groups fed diets containing 0.9, 0.3, and 0.02% Ca, respectively. They were further divided into 2 groups according to pregnancy or non-pregnancy. Animals in the pregnant group were raised with their own pups for lactation. After the experiment, all animals were sacrificed, their mandibles were dissected, and soft x-ray microradiographs were taken to determine BMD in the interdental area with an image analyzer. RESULTS: In both groups, BMD in alveolar bone decreased based on the amount of Ca in the diet, but the magnitude of this decrease was much greater in the pregnant group than in the non-pregnant group. There was no significant difference in BMD between 2 groups fed a 0.9% Ca diet. The BMD of alveolar bone in the pups also decreased depending on the amount of Ca in the diet. CONCLUSIONS: The above results suggest that pregnancy and subsequent lactation could be risk factors for alveolar bone loss, especially under conditions of Ca insufficiency or deficiency and that Ca insufficiency or deficiency in the mother caused decreases in the BMD of alveolar bone in the pups.

Phenytoin and its metabolite, 5-(4-hydroxyphenyl)-5-phenylhydantoin, show bone resorption in cultured neonatal mouse calvaria.

The effects of phenytoin and its major metabolite, 5-(4-hydroxyphenyl)-5-phenylhydantoin (HPPH), on bone resorption of neonatal mouse calvaria were examined in vitro. Both phenytoin and HPPH induced significant bone resorption as compared to the controls after 72 h in culture. This effect may be the cause of phenytoin-induced bone loss in vivo.