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Biomedical subjects

M Chiba

Publications and source records attributed to M Chiba.

At least 19 recordsLinked to original sources

Clinical diagnostic indicators of renal and bone damage in rats intramuscularly injected with depleted uranium.

The toxic effects and changes in biochemical markers related to kidney and bone in depleted uranium (DU)-injected rats were examined in order to clarify the relation between clinical biochemical markers and the degree of damage in these organs. Male Wistar rats received a single injection in the femoral muscles of 0.2, 1.0 or 2.0 mg kg(-1) of DU which was dissolved in nitric acid solution adjusted to pH 3.2, for comparison with the group injected with nitric acid solution, and the control group. Urine and faeces were collected periodically over a 24 h period. Thereafter, the rats were killed at 28 d after DU injection. The body weights of the DU-injected groups decreased dose-dependently for the first 3-7 d, and then began to increase. The DU concentrations in the urine and faeces decreased rapidly within 3-7 d after DU injection. Urinary N-acetyl-beta-D-glucosaminidase (NAG)/creatinine peaked at the third day after DU injection, with a high correlation to the injected DU doses. There were high correlations among the injected DU doses, DU concentrations in the kidney and urinary NAG/creatinine values that were obtained at 28 d, respectively. The blood urea nitrogen (BUN) and creatinine in the serum also showed a high correlation with the DU-injected doses. The results indicated that urinary NAG/creatinine, BUN and creatinine in serum were useful indicators to diagnose the renal damage by DU, as well as to estimate the DU intake and concentration in the kidney when the intake is >2 mg kg(-1) DU. The total bone mineral density of the proximal metaphysis of the tibia decreased in the 2 mg kg(-1) DU group. In addition, alterations of the trabecular bone structure by inhibiting bone formation and promoting bone resorption were observed by bone histomorphometery. The bone biochemical markers osteocalcin, tartrate-resistance acid phosphatase, pyridinoline and rat-parathyroid hormone increased in all the DU injected groups, indicating that these markers were useful as sensitive indicators for diagnosing bone damage, even if the DU dose injected is low.

Animals↗

Local RANKL gene transfer to the periodontal tissue accelerates orthodontic tooth movement.

It has been reported that not only selective alveolar-bone resorption, but also receptor activator of nuclear factor kappa B ligand (RANKL) expression is induced on the compressed side of an orthodontically moving tooth. Numerous reports have described the pharmacological acceleration of tooth movement (TM) through the activation of osteoclasts. However, because of rapid flush out by blood circulation, daily systemic administration or daily local injection is needed. Previously, we discovered that every-3-days OPG gene transfer to the periodontal-tissue inhibited RANKL-mediated osteoclastogenesis and diminished experimental TM. Therefore, we hypothesized that local RANKL gene transfer into the periodontal tissue would accelerate TM. The upper first molars of 6-week-old male Wistar rats were moved palatally using fixed orthodontic wires. The inactivated hemagglutinating-virus of Japan (HVJ) envelope vector containing the mouse RANKL expression plasmid was injected periodically into the palatal periodontal tissue of the upper first molars during TM. Local RANKL gene transfer significantly enhanced RANKL expression and osteoclastogenesis in periodontal tissue without any systemic effects. The TM rate was significantly increased in the RANKL gene transfer side. In conclusion, we demonstrated that transfer of the RANKL gene to the periodontal-tissue activated osteoclastogenesis and accelerated the amount of experimental TM. Local RANKL gene transfer might be a useful tool not only for shortening orthodontic treatment, but also for moving ankylosed teeth where teeth, fuse to the surrounding bone.

Animals↗

Compressive force induces osteoblast apoptosis via caspase-8.

Periodontal remodeling during orthodontic tooth movement is a result of mechanical stresses. The application of excessive orthodontic force induces cell death. However, the nature of compressive force-induced cell death is unclear. We examined whether the in vitro application of continuous compressive force would induce apoptosis in human osteoblast-like cells (MG-63 cells), and investigated the mechanism by which apoptosis was initiated. The cells became aligned irregularly, and cell viability decreased, indicating that the compressive force caused cell death. According to the TUNEL analysis, the number of apoptotic cells increased significantly in a time-and force-dependent manner. Caspase-3 activity increased with the magnitude of the compressive force, and this effect was reduced significantly by a caspase-8 inhibitor, whereas a caspase-9 inhibitor had no such effect. We conclude that the in vitro application of compressive force can induce apoptosis in MG-63 cells through the activation of caspase-3 via the caspase-8 signaling cascade.

Analysis of Variance↗

Cyclical tensile force on periodontal ligament cells inhibits osteoclastogenesis through OPG induction.

The periodontal ligament (PDL) maintains homeostasis of periodontal tissue under mechanical tensile-loading caused by mastication. Occlusal load inhibits atrophic alveolar bone resorption. Previously, we discovered that continuous compressive force on PDL cells induced osteoclastogenesis-supporting activity, with up-regulation of RANKL. We hypothesized that, unlike compression, cyclical tensile force up-regulates OPG expression in PDL cells via TGF-beta up-regulation, and does not induce osteoclastogenesis-supporting activity. PDL cells were mechanically stimulated by cyclical tensile force in vitro. The conditioned media of PDL cells that had been subjected to cyclical tensile force inhibited osteoclastogenesis. Cyclical tensile force up-regulated not only RANKL mRNA expression, but also OPG mRNA expression in PDL cells. Tensile force up-regulated TGF-beta expression in PDL cells as well. Administration of neutralizing antibodies to TGF-beta inhibited OPG up-regulation under cyclical tensile-force stimulation in a dose-dependent manner. Additionally, the osteoclastogenesis-inhibitory effect of the conditioned media of PDL cells under cyclical tensile force was partially rescued by the administration of TGF-beta neutralizing antibodies. In conclusion, tensile force inhibited the osteoclastogenesis-supporting activity of PDL cells by inducing the up-regulation of OPG via TGF-beta stimulation.

Adult↗

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.

Adult↗

Application of boron-entrapped stealth liposomes to inhibition of growth of tumour cells in the in vivo boron neutron-capture therapy model.

Tumour cell destruction in boron neutron-capture therapy (BNCT) is due to the nuclear reaction between (10)B and thermal neutrons. It is necessary for effective BNCT therapy to accumulate (10)B atoms in the tumour cells. The delivery system consisted of polyethylene-glycol (PEG) binding liposomes (DPPC/cholesterol/DSPC-PEG2000) with an entrapped (10)B-compound and we evaluated the cytotoxic effects of intravenously injected (10)B-PEG-liposomes on human pancreatic carcinoma xenografts in nude mice with thermal neutron irradiation. After thermal neutron irradiation of mice injected with (10)B-PEG-liposomes, growth of AsPC-1 tumours was suppressed relative to controls. Injection of (10)B-PEG-liposomes caused the greatest tumour suppression with thermal neutron irradiation in vivo. These results suggest that intravenous injection of (10)B-PEG-liposomes can increase the retention of (10)B atoms by tumour cells, causing suppression of tumour growth in vivo, after thermal neutron irradiation.

Animals↗

The relationship of bone marrow edema pattern in the mandibular condyle with joint pain in patients with temporomandibular joint disorders: longitudinal study with MR imaging.

The purpose of this study was to investigate the course of bone marrow edema pattern (decreased signal intensity on T1- or proton-density-weighted images and increased signal intensity on T2-weighted fat-suppressed images) in the mandibular condyle after improvement in clinical symptoms, and to clarify its relationship with temporomandibular joint (TMJ) pain. This study was based on 14 joints of 11 patients (all female, mean age 37.5 years) with TMJ disorders showing condylar bone marrow edema pattern on initial magnetic resonance (MR) images. All joints were re-evaluated clinically and using MR images after relief of joint pain following arthrocentesis combined with non-surgical treatment. The time interval between the initial and follow-up MR images ranged from 14 to 27 months (mean 17 months). Of the 14 joints, 4 joints (28.6%) showed a normal bone marrow signal, whereas 10 joints (71.4%) showed persistent bone marrow edema pattern on follow-up MR images (P = 0.125). Therefore, the reduction in TMJ pain did not correlate with resolution of bone marrow edema pattern in most joints. The results of this study suggest that the bone marrow edema pattern in the mandibular condyle does not always contribute to the occurrence of joint pain in patients with TMJ disorders.

Adolescent↗

Experimental observation of the 1/3 magnetization plateau in the diamond-chain compound Cu3(CO3)2(OH)2.

The magnetic susceptibility, high field magnetization, and specific heat measurements of Cu3(CO3)2(OH)2, which is a model substance for the frustrating diamond spin chain model, have been performed using single crystals. Two broad peaks are observed at around 20 and 5 K in both magnetic susceptibility and specific heat results. The magnetization curve has a clear plateau at one third of the saturation magnetization. The experimental results are examined in terms of theoretical expectations based on exact diagonalization and density matrix renormalization group methods. An origin of magnetic anisotropy is also discussed.

Journal Article↗

Longitudinal MRI follow-up of temporomandibular joint internal derangement with closed lock after successful disk reduction with mandibular manipulation.

We present a case of bilateral temporomandibular joint (TMJ) internal derangement with closed lock, which was followed over 11 years using serial MRI after successful disk reduction with mandibular manipulation. MRI of the bilateral TMJs before and after mandibular manipulation followed by anterior repositioning splint showed that the disk improved from non-reducible to reducible, and that the reducing disk persisted for 11 years, although minor changes in configuration and position of the disk occurred. These MRI findings suggest that non-surgical treatment with successful mandibular manipulation prevents progressive changes in the TMJ. This case report complements observations regarding the longitudinal course of TMJ internal derangement with closed lock after non-surgical treatment.

Adult↗

Effects of age on the stress-strain and stress-relaxation properties of the rat molar periodontal ligament.

OBJECTIVE: We examined the stress-strain and stress-relaxation properties of the periodontal ligament (PDL) in the rat molar at 2, 6, 12, and 24 months of age to elucidate age-related changes in the tooth support function of the PDL. DESIGN: From the dissected left and right mandibles in each rat, a pair of transverse sections (ca. 0.45 mm in thickness) of the first molar was cut at the middle part of the mesial root. We then obtained a load-deformation curve for the PDL, using one of the paired sections. The other section was loaded to as much as 50% of the maximum load as determined from the contralateral section, and keeping the deformation constant for 10 min, a load-relaxation curve was obtained and analysed. RESULTS: The maximum shear stress and tangent modulus decreased between 2 and 24 months of age. As the maximum shear strain increased with age (P < 0.001), the failure strain energy density did not change between 2 and 24 months of age. The stress-relaxation during the 10 min period decreased from 2 to 24 months of age (P < 0.01). The relaxation process of the PDL in each age was well described by a sum of three exponential decay functions. The age-related decrease in the relaxation was found to be mainly due to the increase in the relaxation time for the long-term relaxation component. CONCLUSION: These results indicate that the maximum shear stress and stiffness of the rat molar PDL decrease between 2 and 24 months of age; but its toughness remains unchanged due to an increase in the extensibility. Our findings further indicate that the fluid flow and movements of macromolecules within the stretched PDL fibres during the stress-relaxation decrease with advancing age.

Aging↗

Age-related and regional differences in the stress-strain and stress-relaxation behaviours of the rat incisor periodontal ligament.

Groups of rats were killed at 2, 6, 12, and 24 months of age. From dissected left and right mandibles in each rat, three pairs of transverse sections were cut at the incisal, middle, and basal regions of the incisor. One section in each pair was loaded until failure and a stress-strain curve for the periodontal ligament (PDL) was obtained. The other section was loaded to up to 50% of the maximum shear stress as determined from the contralateral section and then kept at a constant strain for 10 min, to obtain the stress-relaxation curve at the same region of the PDL. The maximum shear stress and toughness increased with age at the incisal region and the maximum shear strain increased with age at the incisal and middle regions. The tangent modulus decreased with advancing age at the middle region. The stress-relaxation during 10 min decreased with advancing age at the incisal and basal regions, but not at the middle region. The relaxation process was well described by a sum of three exponential decay functions, reflecting the short-, medium-, and long-term relaxation components. The age-related decrease in the relaxation was mainly attributable to increases in the ratio and relaxation time of the long-term relaxation component. These results suggest that with advancing age the mechanical strength and toughness of the PDL are enhanced mostly at the incisal region and that the viscous fraction is relatively decreased at the incisal and basal regions along the long axis of the rat incisor.

Aging↗

Closure of a cervical H-type tracheoesophageal fistula.

Congenital H-type tracheoesophageal fistulae in adults are infrequent. In surgery, the essential components (defining, cutting, and suturing the fistula, and preventive interposition of muscle flap) must be performed precisely. We undertook these procedures through a small collar incision. Based on results of preoperative images, the fistula was identified under minimum dissection between the trachea and esophagus. After cutting and suturing the fistula, a sternohyoid muscle flap was interposed.

Adolescent↗

Anaemia in relation to low bioavailability of dietary iron among school-aged children in the Aral Sea region, Kazakhstan.

This study investigates anaemia related to the sufficiency of dietary iron intake of school-aged children in the Kzyl-Orda region of Kazakhstan. We conducted a cross-sectional study of 97 school-aged children living in Kzyl-Orda. Blood samples were collected for measuring haemoglobin. Dietary intake data were obtained from 24-h dietary recalls. Iron bioavailability was estimated with algorithms adjusting for absorption enhancers (meat, fish and poultry, and vitamin C) and inhibitors (tea and phytates) consumed in the same meal. The median total iron intakes were adequate compared with the median basal iron requirement; however, the median bioavailable iron intakes were well below the median absorbed iron requirement. Available iron was 6.9-7.2% of the total iron intake after adjusting for the absorption enhancers, and was reduced by 3.1-4.4% after adjusting for both enhancers and inhibitors. After adjustment for energy intake, higher iron intake was significantly associated with a decreased prevalence of anaemia (odds ratio, 0.39; 95% confidence interval, 0.16-0.93; P=0.034). Some evidence suggested an association between bioavailable iron intake after adjustment of absorption enhancers and inhibitors (odds ratio, 0.43; 95% confidence interval, 0.18-1.01; P=0.053). In conclusion, low bioavailability of dietary iron seems related to anaemia in the region. Although iron fortification or supplementation programmes can be useful for promoting the anaemia prevention control programme, further efforts for nutritional education suited for family level dietary practice are necessary.

Absorption↗

Effects of alendronate on restoration of biomechanical properties of periodontium in replanted rat molars.

OBJECTIVE: We examined the effect of the pretreatment of roots with alendronate on the restoration of the support function of the healing periodontal ligament in replanted rat molars. METHODS: The left maxillary first molars were extracted, placed in 0.9% NaCl containing 1 mm alendronate (alendronate group) or 0.9% NaCl (control group) for 5 min, and were replanted into their sockets. Groups of animals were killed at 7, 14, and 21 days after replantation. Normal control rats were also killed on the same days. The force required to extract the replanted or normal tooth from its socket was measured, and a load-deformation curve was developed and analyzed. Micro-computed tomography and histologic analyses were also made. RESULTS: The mechanical properties of the healing periodontal ligament in the alendronate group were gradually restored from 7 to 21 days. However, fractures of the roots and bones during mechanical testing occurred in most of the replanted teeth in the control group at 21 days. The rates of restoration of the mechanical strength, extensibility, stiffness, and toughness for the alendronate group at 21 days were 67, 98, 74, and 68% of the normal controls, respectively. Micro-computed tomography and histologic observations revealed that bone-like structures within the pulp and ankylosis between the roots and socket bones occurred commonly in the control group, but were uncommon in the alendronate group. CONCLUSIONS: Our findings suggest that the pretreatment with alendronate inhibits the formation of abnormal mineralized tissues and results in better restoration of the support function of the healing periodontal ligament in replanted teeth.

Alendronate↗

Local OPG gene transfer to periodontal tissue inhibits orthodontic tooth movement.

Previously, we discovered that RANKL expression is induced in compressed periodontal ligament cells, and that this promotes osteoclastogenesis on the compression side in orthodontic tooth movement. We hypothesized that local OPG gene transfer to the periodontium would neutralize the RANKL activity induced by mechanical compressive force, thereby inhibiting osteoclastogenesis and diminishing tooth movement. The upper first molars of six-week-old male Wistar rats were moved palatally by means of a fixed-orthodontic wire. A mouse OPG expression plasmid [pcDNA3.1(+)-mOPG] was constructed, and the production of functional OPG protein was confirmed in vitro. The inactivated HVJ envelope vector containing pcDNA3.1(+)-mOPG or PBS was injected periodically into the palatal periodontal tissue of upper first molars. When this local OPG gene transfer was performed, OPG production was induced, and osteoclastogenesis was inhibited. Local OPG gene transfer significantly diminished tooth movement. In this study, we report that OPG gene transfer to periodontal tissue inhibited RANKL-mediated osteoclastogenesis and inhibited experimental tooth movement.

Animals↗

The effects of intrusive loading on axial movements of impeded and unimpeded rat incisors: estimation of eruptive force.

Axial movements of impeded and unimpeded rat mandibular incisors were measured following application and removal of intrusive loads of 1, 2, 5, 10 and 20 mN in a stepwise order at intervals of 1h on erupting teeth. The tooth movements were recorded by a displacement detector under artificial respiration with halothane anaesthesia. The loading and unloading procedures brought about the tooth movements in two steps: an initial rapid movement immediately after application or removal of the load and a subsequent slow and gradual movement. The initial rapid intrusive or extrusive tooth movements were significantly greater in the unimpeded than in the impeded teeth at the same load. The forces to stop extrusive tooth movements, estimated from the formula of regression lines showing correlations between the intrusive loads from 0 to 5 mN and tooth movements (microm/30 min), were 4.2 mN in the impeded and 2.9 mN in the unimpeded incisors. We suggest that repeated shortenings of the rat incisor did not cause an increase in the eruptive force and that changes in the resistance of the periodontal ligament predominantly regulate the axial movement of the rat incisor.

Animals↗

Interaction with indinavir to enhance systemic exposure of an investigational HIV protease inhibitor in rats, dogs and monkeys.

1. The use of a beneficial interaction between indinavir and compound A, a potent investigational HIV protease inhibitor to enhance systemic exposure of compound A, was investigated. 2. When administrated alone, compound A underwent extensive hepatic first-pass metabolism in rats and monkeys, resulting in low oral bioavailability. 3. In vitro studies with liver microsomes revealed that compound A metabolism was mediated exclusively by CYP3A enzymes in rats, dogs and monkeys. Indinavir, which also was metabolized predominantly by CYP3A enzymes, extensively inhibited compound A metabolism in microsomes, whereas compound A showed weak inhibitory potency on indinavir metabolism. 4. Consistent with in vitro observations, co-administration of the two compounds resulted in a 17-fold increase in oral AUC of compound A in rats owing to the inhibition of metabolism of compound A by indinavir, whereas compound A did not affect indinavir metabolism as indicated by the unchanged indinavir AUC. Similarly, the systemic exposure of compound A in dogs and monkeys was increased substantially following oral co-administration with indinavir by 7- and > 50-fold, respectively. 5. Enhancement in compound A systemic exposure by indinavir in humans, as predicted based on the in vivo animal and in vitro human liver microsomal data, was confirmed in subsequent clinical studies.

Animals↗

Anemia and iron deficiency among schoolchildren in the Aral Sea region, Kazakhstan.

The objectives of this study were to estimate the prevalence of anemia and iron deficiency among schoolchildren in the Aral Sea region of Kazakhstan and to determine the various factors associated with anemia in this population. We conducted a cross-sectional study of randomly selected schoolchildren. Blood samples were collected for measuring hemoglobin (Hb), serum ferritin (SF), total iron binding capacity (TIBC), and other hematological indices, and subjects were screened for anemia and iron deficiency. Associations between Hb concentration and SF, TIBC, anthropometric, and socioeconomic data were evaluated using regression analysis. The prevalence of anemia was 49.8 per cent although levels were mostly mild. Twenty-two per cent of the children were iron depleted (SF < 12 microg/l). Of the anemic children, 32.4 per cent were found to have iron deficiency anemia (anemia with SF < 12 microg/l). There were significant positive correlations between the levels of Hb and SF, but a negative correlation with serum TIBC. Age, mean corpuscular volume (MCV) and SF were found to be significantly related to Hb by stepwise multiple regression analysis. Multiple logistic regression analysis revealed that anemia was independently related to living district, education of father, and child's age. The results suggest that iron deficiency is an important determinant of anemia in this population; however, whole anemia cannot be solely explained by iron deficiency. Further studies are needed for consideration of micronutrients status, parasite infestation, hereditary disorders, and exposure to environmental pollutants.

Adolescent↗