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Biomedical subjects

Toshitaka Nakamura

Publications and source records attributed to Toshitaka Nakamura.

At least 37 records · Page 2Linked to original sources
PubMed2006

Clinical study of cerebrospinal fluid dynamics using 111In-DTPA SPECT in patients with subarachnoid hemorrhage.

The ventricle-to-background ratio and clearance rate constant measured by indium-111 diethylenetriaminepenta-acetic acid single photon emission computed tomography ((111)In-DTPA SPECT) were evaluated for predicting hydrocephalus in 16 patients at 2 to 3 weeks after onset of subarachnoid hemorrhage. The activity in the lateral ventricles, basal cistern, and hemispheric convexities was measured at 6, 24, and 48 hours after lumbar injection of radionuclide. In the follow-up study, eight patients developed hydrocephalus, and required ventriculoperitoneal shunting. Radioactivity measured in the hemispheric convexity did not reach peak activity within 48 hours. The clearance rate measured by applying the mono-exponential equation failed to show delayed clearance of radionuclide in hydrocephalus. The ratio between the ventricle and basal cistern measured at 6 hours postinjection was the best predictor of hydrocephalus (F(1, 30) = 42.84, p < 0.0001). These results suggest that a single (111)In-DTPA SPECT scan may be sufficient to identify patients at risk of developing hydrocephalus.

Aged↗
PubMed2006

[Degenerative disorders of the skeleton in elderly].

Skeletal degeneration such as osteoporosis and osteoarthritis increases morbidity and mortality of aged persons. It is associated with inflammation induced by micro particles from bone and cartilage matrices and reduction in bone quality that could be due to disturbance of regulatory function of bone mass and structure in response to mechanical loading. Deformity in the skeletons induced by osteoporosis and osteoarthritis is irreversible and accumulating. To establish the substantial methods to alleviate it, we need to know the effects of gonad hormone deficiency underlying in the diseases.

Aged↗
PubMed2006

[Functional mechanism of glucocorticoid in bone turnover and bone structure].

The functional mechanism of glucocorticoid (GC)-induced osteoporosis is not fully understood. We examined to the effects of GC on bone turnover, minerals, structure, and bone strength in growing minipigs. GC administration caused prolongation of the period of bone tissue turnover in both trabecular and cortical bone and imbalance in bone formation and resorption, consequently leading to osteoporosis in growing minipigs. Bone structure were deteriorated both trabeculare and cortex. Deterioration of cortical bone rather than trabecular bone could play a role as main factor of bone fragilities in GC-induced osteoporosis.

Animals↗
PubMed2006

[Prevention of osteoporotic fracture by pharmaceutical interventions].

Osteoporosis has been successfully treated with anti-resorptive agents. Estrogen, ever regarded as the gold standard in the treatment of osteoporosis, has now been considered as one of the second line agents. Calcium and vitamin D still remain useful as important basic nutrients, given in combination with anti-resorptive treatments. Nitrogen containing bisphosphonates such as alendronate and risedronate and raloxifene have become the standard therapeutic agents in Japan, but their efficacies in prevention of vertebral and non-vertebral fractures are not completely similar. It has been established that BMD increase is not the primary factor on the prevention of vertebral fracture, but BMD increases seem to be critical to reduce the risk of non-vertebral fractures by anti-resorptive agents. Efficacy of combination of anti-resorptive agents with different action mechanisms such as bisphosphonates and raloxifene has not yet been established whether the combination further reduces the risk of non-vertebral fractures.

Bone Density Conservation Agents↗
PubMed2005

A new active vitamin D, ED-71, increases bone mass in osteoporotic patients under vitamin D supplementation: a randomized, double-blind, placebo-controlled clinical trial.

CONTEXT: ED-71 has been shown to increase lumbar bone mineral density (BMD) in osteoporotic subjects. However, vitamin D insufficiency might have influenced the effect of ED-71 on BMD. OBJECTIVE: Our objective was to examine whether ED-71 can increase BMD in osteoporotic patients under vitamin D supplementation. DESIGN, SETTING, AND PATIENTS: We conducted a randomized, double-blind, placebo-controlled clinical trial of 219 osteoporotic patients (49-87 yr of age). INTERVENTIONS: Subjects were randomly assigned to receive placebo or 0.5, 0.75, or 1.0 microg/d ED-71 for 12 months. All the subjects received 200 or 400 IU/d vitamin D(3). MAIN OUTCOME MEASURES: We assessed changes in lumbar and hip BMD and bone turnover markers from baseline. RESULTS: Lumbar BMD increased with ED-71 treatment for 12 months (2.2, 2.6, and 3.1% from baseline and 2.9, 3.4, and 3.8% vs. placebo group in subjects receiving 0.5, 0.75, and 1.0 microg ED-71, respectively). Total hip BMD also increased with 0.75 and 1.0 microg ED-71 (-0.8, 0.6, and 0.9% from baseline and 0.1, 1.5, and 1.8% vs. placebo group in the 0.5, 0.75, and 1.0 microg ED-71 groups, respectively). Bone formation and resorption markers were suppressed by approximately 20% after 12 months of 0.75 and 1.0 microg ED-71 treatment. Transient hypercalcemia over 2.6 mmol/liter occurred in 7, 5, and 23% of subjects in the 0.5, 0.75, and 1.0 microg ED-71 groups, respectively, but none of them developed sustained hypercalcemia. CONCLUSIONS: These results demonstrate that ED-71 treatment at around 0.75 microg/d can effectively and safely increase lumbar and hip BMD in osteoporotic patients with vitamin D supplementation.

Absorptiometry, Photon↗
PubMed2005

Induction of galanin-like peptide gene expression in the arcuate nucleus of the rat after acute but not chronic inflammatory stress.

Galanin-like peptide (GALP) has been recently isolated from the porcine hypothalamus. The GALP mRNA is restricted to neurons in the hypothalamic arcuate nucleus (Arc) and pituicytes in the posterior pituitary gland (PP), but physiological functions of the GALP remains unclear in both areas. We examined the effects of acute and chronic inflammatory stresses on the GALP mRNA levels in the rat Arc using in situ hybridization histochemistry. Intraperitoneal (i.p.) injection of bacterial endotoxin lipopolysaccharide (LPS) caused a marked increase of the GALP mRNA levels in the Arc. The effects of i.p. injection of LPS on the GALP mRNA levels in the Arc were significantly attenuated by pretreatment with i.p. injection of indomethacin cyclooxygenase inhibitor. Adjuvant arthritis caused by subcutaneous (s.c.) injection of heat-killed Mycobacterium butyricum as chronic inflammatory stress did not affect the GALP mRNA levels in the Arc, though the GALP mRNA levels in the pituicytes of the PP were markedly increased by two peaks at 12 h and 15 days after s.c. injection of heat-killed M. butyricum. Enzymeimmunoassay showed that the plasma concentration of GALP was not affected by these inflammatory stresses. These results suggest that acute inflammatory stress might be a potent stimulant to increase the GALP mRNA levels in the Arc of the rat via synthesis of prostaglandins.

Analysis of Variance↗
PubMed2005

Reduced expression of platelet endothelial cell adhesion molecule-1 in bone marrow cells in mice after skeletal unloading.

UNLABELLED: One week of tail suspension significantly decreased the expression of PECAM-1 in mouse tibial bone marrow cells but not those of a number of other vascular factors. Anti-PECAM-1 antibody suppressed both ALP+ CFU-f formation and ALP production under co-culture of the osteoblastic cell line and the PECAM-1+ endothelial cell line. This study suggests that the reduced ALP activity after skeletal unloading is related to downregulation of PECAM-1 expression in bone marrow cells in mice. INTRODUCTION: Vascular factors play a role in bone development and regeneration. We tested the hypothesis that skeletal unloading reduces osteogenic potential by inhibiting the molecules related to angiogenesis and/or vasculogenesis in bone marrow cells. MATERIALS AND METHODS: Eight-week-old male mice were assigned to three groups after acclimatization for 1 week: ground control (GC), tail suspension (TS), and reloading after 7-day TS (RL). Bilateral tibial and humeral samples were used for analyses. MC3T3-E1, a mouse osteoblastic cell line, and EOMA and ISOS-1, mouse endothelial cell lines, were also used. RESULTS: Flow cytometric analysis revealed that 7-day TS significantly decreased the expression of platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) in tibial bone marrow cells, but not those of angiopoietin-1, angiopoietin-2, Flk-1 (vascular endothelial growth factor receptor-2), and vascular endothelial cadherin. The expression of PECAM-1 in tibial marrow cells was reduced at day 3 of TS to 80% and still showed significantly low levels at day 7 of TS to 72% of that at the respective days of GC. This decreased expression of PECAM-1 after 7-day TS showed the GC level at 5-day reloading after 7-day TS. However, the expression of PECAM-1 in humeral marrow cells (internal bone marrow control) after TS and RL remained unchanged and equivalent to that of GC. The expression level of PECAM-1 mRNA was significantly lower at day 7 of TS to 62% of that in GC. Double labeling analyses revealed that PECAM-1+ cells mostly consisted of endothelial cells and partially of granulocytes. In bone marrow cell cultures, the formation of alkaline phosphatase (ALP)+ colony forming units-fibroblastic was significantly reduced in the presence of anti-PECAM-1 antibody in the medium compared with the presence of immunoglobulin G (0.025 times as much as ALP production with immunoglobulin G). ALP production by cultured MC3T3-E1 was enhanced in combination with PECAM-1+ EOMA (1.8 times as much as ALP production by MC3T3-E1 alone), but not in combination with PECAM-1- ISOS-1. Anti-PECAM-1 antibody inhibited the increase in ALP production under co-culture with EOMA. CONCLUSIONS: Our data show that the reduced ALP activity after skeletal unloading is closely correlated with reduced expression of PECAM-1 in bone marrow cells. We speculate that the loss of osteogenic potential after skeletal unloading is caused by the suppression of PECAM-1 signaling on endothelial cellular surface.

3T3 Cells↗
PubMed2005

Osteoclast development in immobilized bone is suppressed by parathyroidectomy in mice.

We tested the hypothesis that signaling of parathyroid hormone (PTH) facilitates osteoclastogenesis in bone marrow cells after immobilization, thereby reducing trabecular bone volume. We performed histomorphometric analyses in immobilized limbs after right sciatic neurectomy (IM) and in the contralateral limbs after sham surgery (M). Mice underwent thyroparathyroidectomy (TPTX) and then 0.2 microg/body of thyroxine was given three times a week, or the mice were subjected to sham surgery (sham). Six-week-old male ddY mice were assigned to four groups, as follows, after acclimatization for 1 week: M + sham, IM + sham; M + TPTX, and IM + TPTX. Bilateral tibial samples were used for analysis. Trabecular bone volume (BV/TV) in the secondary spongiosa of the proximal tibias in IM + sham was significantly reduced compared to that in M + sham. Osteoclast surface (Oc.S/BS) and number (Oc.N/BS) in IM + sham transiently increased at 3 and 4 weeks after IM. In contrast, TPTX partially prevented the IM-related reduction of BV/TV and completely suppressed the transient increases of Oc.S/BS and Oc.N/BS. In the bone marrow cells, the mRNA expression of RANKL was elevated in IM + sham, but not in IM + TPTX, compared to that in M + sham. The percentage of Mac-1-positive bone marrow cells, osteoclast precursors, was not altered after IM. There were no significant differences in the concentrations of interleukin (IL)-1alpha in the tibial bone marrow cell culture medium between M + sham and IM + sham. Our data demonstrated that significant increases in osteoclast surface and number after IM were suppressed in TPTX mice, closely associated with a reduction in the high expression of RANKL mRNA in the tibial bone marrow cells. We speculate that enhanced osteoclastogenesis due to limb immobilization may be related to the elevation of RANKL expression by the facilitation of parathyroid hormone signaling in bone marrow cells.

Animals↗
PubMed2005

Modulation of bone turnover by alfacalcidol and/or alendronate does not prevent glucocorticoid-induced osteoporosis in growing minipigs.

The study was performed to clarify the effects of active vitamin D (alfacalcidol) and/or alendronate (ALN) on bone tissue turnover in glucocorticoid (GC)-treated growing minipigs. Göttingen minipigs aged 8 months were divided into six groups (n = 5 each): group BC, killed for baseline control; group GC, injected subcutaneously with prednisolone (0.5 mg/kg body weight [BW] per day, 5 days/week for 24 weeks); group VC, treated with vehicle alone; group alf, treated with oral alfacalcidol at 0.1 microm/kg BW per day, 5 days/week; group ALN, treated with alendronate 1 mg/kg BW per day; and group alf* ALN, treated with both alf and ALN as above. Biochemical examinations dual-energy X-ray absorptiometry, micro-computed tomography, peripheral quantitative computed tomography, and histomorphometry were performed. In group GC, all bone chemical markers were lower than in group VC. GC treatment reduced the age-dependent augmentation of bone mass and structure by reducing the bone formation rate (BFR) and activation frequency (Ac.f) relative to VC in lumbar bone and femoral cortex. Trabecular and osteonal wall thickness values did not change by GC. Treatments with alf, ALN, and alf* ALN did not have substantial effects on bone mass or structure. Alf treatment maintained lumbar BFR and Ac.f, while ALN reduced osteoclasts. Femoral cortical Ac.f values were not affected by these treatments. GC caused reduced bone formation, leading to low tissue turnover and imbalance of bone formation and resorption. Modulation of bone tissue turnover by alfacalcidol and/or alendronate failed to maintain the growth-dependent increases in mass and structure in GC-treated young minipigs.

Absorptiometry, Photon↗
PubMed2005

Therapeutic effects of alendronate 35 mg once weekly and 5 mg once daily in Japanese patients with osteoporosis: a double-blind, randomized study.

The efficacy and safety of treatment with oral alendronate (ALN) 35 mg once weekly for 52 weeks were compared with those of ALN 5 mg once daily in a double-blind, randomized, multicenter study of Japanese patients with involutional osteoporosis. The primary efficacy end point was the percent change from baseline in the lumbar spine (L1-L4) bone mineral density (BMD) after 52 weeks of treatment. In this study, 328 patients were randomized to ALN 5 mg once daily (160 patients) or ALN 35 mg once weekly (168 patients). The adjusted mean percent change from baseline in lumbar spine (L1-L4) BMD after 52 weeks of treatment was 5.8% and 6.4% in the once-daily group and the once-weekly group, respectively (both P < 0.001). The 95% confidence interval for the difference in spine BMD change between the two treatment groups was -0.31% to 1.48%, indicating that the two regimens were therapeutically equivalent, since the confidence interval fell entirely within the predefined equivalence criterion (+/-1.5%). The time course of the spine BMD increase was also similar for both regimens. Regarding total hip BMD, mean changes from baseline at 52 weeks were 2.8% and 3.0% in the once-daily group and the once-weekly group, respectively. In addition, the bone markers (urinary deoxypyridinoline, urinary type-I collagen N-telopeptides, and serum bone-specific alkaline phosphatase) were reduced to a similar level by either treatment throughout the treatment period. The tolerability and safety profiles were also similar between the treatment groups. Taken together, we conclude that the efficacy and safety of the ALN 35-mg once-weekly regimen are therapeutically equivalent to those of the ALN 5-mg once-daily regimen.

Adult↗
PubMed2005

Bisphosphonate (YM529) delays the repair of cortical bone defect after drill-hole injury by reducing terminal differentiation of osteoblasts in the mouse femur.

We evaluated the effects of YM529, a nitrogen-containing bisphosphonate, on the repair of cortical bone after drill-hole injury at the tissue-, cell- and gene-levels in the femur of mice. Eight-week-old male C57BL/6N mice were treated with an intravenous injection of 0.01, 0.05 and 0.1 mg/kg body weight (BW) of YM529, or the vehicle (VC) once a week from 8 weeks of age until sacrifice. At 10 weeks of age (day 0), a drill-hole was made in the diaphysis of bilateral femurs. Femoral specimens were obtained at days 3, 5, 7, 10, 14, 21 and 28 after surgery. Histology and histomorphometry confirmed the early woven bone formation in 7 days after injury in all four groups, but the following lamellar bone repair in the cortical tissue area delayed only in the YM529-treated groups. Since the findings were not dose-dependent, following evaluations were performed in VC and YM529 0.1 mg/kg BW dose groups. Calcein-labeled surface of regenerated bone decreased at day 21 in the YM529 group. At day 0, CFU-f number and mineralized nodule area that developed from marrow cells were significantly smaller in YM529 group than in VC group. At day 5, however, these values increased to levels similar to those in VC group. The mRNA expression levels of BMP-2, cbfa1, osterix, type I collagen, and osteocalcin in the injured bone and marrow cells at days 3 and 5 were similar in the two groups, but were higher in YM529 group at day 7 compared with that in the VC group. At day 14, the levels of these mRNAs were still high, while that of osteocalcin was significantly reduced compared to the VC group. These data indicate that the action of YM529 on bone formation is bimodal, stimulatory on the developments of osteogenic cells for the woven bone regeneration and inhibitory on the terminal differentiation of osteoblasts for the later remodeling, consequently leading to a delay in the lamellar bone healing in the cortical tissue area.

Animals↗
PubMed2005

[Indication and significance of pharmacological intervention for back pain].

Back pain is divided into two phases; acute pain is due to the increased signal from the nociceptive receptors in the nerve endings and chronic pain is resulting from the reconstruction of the new nervous net work during the healing stage. Use of NSAIDs and opioids is indicated for the acute pain that is not eased by taking a rest. NSAIDs is also profitable to control chronic pain, but NSAIDs has complications of renal and digestive functions. Persons with ages of more than 65 are especially liable to those dysfunctions. Pharmacological intervention on back pain may not only give the therapeutic benefits but also it can provide the clues for the elucidation of the mechanism and the new therapeutic interventions.

Acute Disease↗
PubMed2005

[Trends in the determination of pharmacological intervention for osteoporosis].

WHO scientific group proposed a new strategy to identify cases for pharmacological intervention by integrating multiple factors of fracture risk. Ten independent risk factors for femoral neck fracture were presented including BMD (bone mineral density), previous fracture, bone chemical markers, and low body weight also their respective relative risk values. After adjusted for population risk, these factors were multiplied to obtain the integrated relative risk values. Then, nomograms were made to represent 10 year-fracture risk values to ages depending on the synthetic risk values. WHO group proposed to pharmacologically intervene when 10-yr risk values of femoral neck fracture exceeds 10-15%. It is a subject in many countries how they evaluate such a case-finding strategy for pharmacological intervention.

Aged↗
PubMed2005

[Osteoporosis and bone quality referred in NIH consensus 2000].

National Institute of Health Consensus Development Conference Statement 2000 included four main items. They were;definition of osteoporosis and fracture risk, different fracture risks among different segments of the population, factors for building and maintaining skeletal health throughout life, and evaluation and treatment of osteoporosis. It is clearly documented in the statement that bone strength reflects the integration of bone density and bone quality, and that evaluation of fracture in osteoporosis should depend on risk-based assessment rather than solely on the assessment of a BMD T-score. These issues indicate a new direction in the management of osteoporosis in near future.

Bone Density↗
PubMed2005

[Development of fracture risk assessment tool (FRAT) by WHO study group and its proposed application].

Risk factors for fragility fracture include BMD and other factors independent from BMD. WHO-study group has proposed a new strategy to establish international tool to estimate absolute risk values for the occurrence of femoral neck fracture at the individual levels, named as fracture risk assessment tool (FRAT). The tool issued from the group is basically derived from the integration of the data of various risk factors obtained in Sweden. It may be useful to identify cases for pharmacological intervention. However, the differences in the kinds and the relative values of fracture risks in other countries or districts have not yet been clarified. Utility of the tool may depend on the results of calibration and validation based on their own data in other districts.

Aged↗
PubMed2004

Intravenous pamidronate prevents femoral bone loss and renal stone formation during 90-day bed rest.

UNLABELLED: Long-term bed rest has potential risks of bone loss and renal stone formation. We examined the effects of resistive exercise and intravenous pamidronate on BMD, bone turnover, urinary calcium, and renal stone formation in 25 healthy males during 90-day bed rest. Pamidronate prevented femoral bone loss and renal stone formation, but resistive exercise showed little effects. INTRODUCTION: Long-term bed rest increases the risks of bone loss and urinary stone formation. Resistive exercise increases bone formation, and bisphosphonates reduce bone resorption. However, the effects of muscle exercise and bisphosphonates have not been examined side-by-side. The objectives of this study are to compare the effects of pamidronate with resistive exercise on BMD and renal stone formation during prolonged bed rest. MATERIALS AND METHODS: Twenty-five male white volunteers, 26-45 years of age, were randomly assigned to the control (n = 9), exercise (n = 9), and pamidronate (n = 7) groups and underwent 90-day 6 degrees head-down tilt bed rest. Exercise group performed squats and heel raises on a flywheel device for 30 minutes every 3 days. Pamidronate (60 mg) was administered intravenously 14 days before bed rest. BMD of the head, forearm, lumbar spine, and proximal femur; biochemical bone markers; calcium (Ca) metabolism; and abdominal radiographs were examined during 90 days of bed rest and 360 days of reloading. RESULTS: In controls, proximal femoral BMD decreased, and bone resorption markers and urinary Ca increased during bed rest, along with development of renal stones in two of nine subjects. Resistive exercise increased bone formation but was unable to prevent femoral BMD decrease and increases in bone resorption and urinary Ca during bed rest, with formation of renal stones in four of nine subjects. Pamidronate maintained femoral BMD, reduced bone resorption and urinary Ca, and completely prevented renal stone formation. CONCLUSIONS: Resistive exercise increased bone formation but could not reduce bone resorption and the risk of renal stones. In contrast, inhibition of bone resorption by pamidronate could preserve bone mineral and reduce the risk of renal stone formation during prolonged bed rest.

Adult↗