Hamri Co.

Ibaraki, Japan

Hamri Co.

Ibaraki, Japan

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To understand sleep mechanisms and develop treatments for sleep disorders, investigations using animal models are essential. The sleep architecture of rodents differs from that of diurnal mammals including humans and non-human primates. Sleep studies have been conducted in non-human primates; however, these sleep assessments were performed on animals placed in a restraint chair connected via the umbilical area to the recording apparatus. To avoid restraints, cables, and other stressful apparatuses and manipulations, telemetry systems have been developed. In the present study, sleep recordings in unrestrained cynomolgus monkeys (Macaca fascicularis) and common marmoset monkeys (Callithrix jacchus) were conducted to characterize normal sleep. For the analysis of sleep-wake rhythms in cynomolgus monkeys, telemetry electroencephalography (EEG), electromyography (EMG), and electrooculography (EOG) signals were used. For the analysis of sleep-wake rhythms in marmosets, telemetry EEG and EOG signals were used. Both monkey species showed monophasic sleep patterns during the dark phase. Although non-rapid eye movement (NREM) deep sleep showed higher levels at the beginning of the dark phase in cynomolgus monkeys, NREM deep sleep rarely occurred during the dark phase in marmosets. Our results indicate that the use of telemetry in non-human primate models is useful for sleep studies, and that the different NREM deep sleep activities between cynomolgus monkeys and common marmoset monkeys are useful to examine sleep functions.


The purpose of the present study was to determine whether teriparatide and monthly minodronic acid would have an additive effect on cancellous bone mass in ovariectomized rats. Seven-week-old female Sprague-Dawley rats were randomized into five groups of 10 animals each, including a sham-operation. +. vehicle group, an ovariectomy (OVX). +. vehicle group, an OVX. +. minodronic acid (6. μg/kg. s.c., every 4. weeks) group, an OVX. +. teriparatide (20. μg/kg. s.c., daily) group, and an OVX. +. minodronic acid. +. teriparatide group. After the 12-week experimental period, static and dynamic histomorphometric analyses were performed on the cancellous bone of the tibial proximal metaphysis. OVX decreased the bone volume per total volume (BV/TV) and the trabecular number (Tb.N) and increased the trabecular separation (Tb.Sp) as a result of increased bone remodeling. Minodronic acid prevented the OVX-induced decreases in BV/TV, while teriparatide increased the BV/TV and trabecular width (Tb.Wi) beyond the values of the sham controls. Minodronic acid prevented, but teriparatide only mitigated, the OVX-induced decrease in Tb.N, although both drugs similarly prevented the OVX-induced increase in Tb.Sp. A combination of teriparatide and minodronic acid further increased the BV/TV and Tb.N and decreased the Tb.Sp as a result of the suppression of bone remodeling, compared with teriparatide alone. These results suggest the differential effect of teriparatide and monthly minodronic acid on cancellous bone structure and the additive effect of the two drugs on cancellous bone mass in OVX rats. © 2014 Elsevier Inc.


Iwamoto J.,Keio University | Seki A.,Hamri Co. | Sato Y.,Mitate Hospital | Matsumoto H.,Keio University
Calcified Tissue International | Year: 2012

Renal insufficiency induces cortical bone loss in rats. The present study examined the influence of vitamin K 2 on renal function, cortical bone mass, and bone strength in rats with renal insufficiency. Thirty male Sprague-Dawley rats (8 weeks old) were randomized by the stratified weight method to the following three groups of 10 animals each: sham operation (control), 5/6 nephrectomy, and 5/6 nephrectomy + oral vitamin K 2 (menaquinone-4, menatetrenone, 30 mg/kg, 5 days/week). Treatment was initiated 10 days after surgery. After 6 weeks of treatment, samples of serum, urine, and bone (femur and tibia) were obtained. Renal function was evaluated, bone histomorphometric analysis was performed on the tibial diaphysis, and the bone mineral density (BMD) and mechanical strength of the femoral diaphysis were determined by peripheral quantitative computed tomography and a three-point bending test, respectively. Nephrectomy induced renal dysfunction, as indicated by increased levels of serum creatinine and urea nitrogen along with a decrease of creatinine clearance; and it also decreased BMD without significantly affecting bone strength at the femoral diaphysis. Vitamin K 2 improved renal function parameters but did not significantly influence BMD at the femoral diaphysis. However, vitamin K 2 decreased the bone marrow area of the tibial diaphysis and increased the stiffness of the femoral diaphysis. These findings suggest that administration of vitamin K 2 improves renal function and increases cortical bone strength without altering BMD in rats with renal insufficiency. © 2011 Springer Science+Business Media, LLC.


Iwamoto J.,Keio University | Seki A.,Hamri Co. | Sato Y.,Mitate Hospital
Chinese Journal of Physiology | Year: 2014

High-dose glucocorticoids reduce cortical bone gain in rats. The aim of the present study was to examine the effect of the intermittent administration of human parathyroid hormone (1-34) (hPTH[1-34]) on cortical bone in rats treated with high-dose prednisolone (PSL). Twenty-five female Sprague-Dawley rats (6 weeks old) were randomized into the following three groups: a vehicle administration (control) group, a PSL (10 mg/kg s.c., 5 times a week) administration group, and a PSL + hPTH(1-34) (30 μg/kg s.c., 3 times a week) administration group. After 8 weeks of treatment, the bone mineral density (BMD) of the femoral diaphysis was determined using peripheral quantitative computed tomography, and a static bone histomorphometric analysis was performed on the tibial diaphysis. PSL administration induced a decrease in the BMD of the femoral diaphysis, compared with the control group, as well as decreases in the total tissue area, cortical area, percent cortical area, and periosteal perimeter and increases in the marrow area, percent marrow area, and endocortical perimeter of the tibial diaphysis, compared with the control group. The intermittent administration of hPTH(1-34) to PSL-treated rats attenuated PSL-related changes in the BMD of the femoral diaphysis and the percent cortical area, marrow area, percent marrow area, and endocortical perimeter of the tibial diaphysis. The findings of the present study suggest that the intermittent administration of hPTH(1-34) improves cortical BMD, acts on the endocortical bone surface, and improves cortical bone geometry, in rats treated with highdose PSL. © 2014 by The Chinese Physiological Society and Airiti Press Inc.


Iwamoto J.,Keio University | Seki A.,Hamri Co. | Sato Y.,Mitate Hospital | Matsumoto H.,Keio University | And 2 more authors.
Calcified Tissue International | Year: 2010

The purpose of the present preclinical study was to determine whether vitamin K2 would promote bone healing in a rat femoral osteotomy model with or without glucocorticoid (GC) treatment. Thirty-eight 6 week-old female Sprague-Dawley rats underwent a unilateral osteotomy of the femoral diaphysis followed by intramedullary wire fixation and then were randomized into four groups that received the following treatment schedules: vehicle, vitamin K2, GC + vehicle, and GC + vitamin K2. GC (prednisolone, 2.5 mg/kg) was administered subcutaneously twice a week. Vitamin K2 (menatetrenone, 30 mg/ kg) was administered orally five times a week. After 8 weeks of treatment, the wires were removed and a bone histomorphometric analysis was performed on the bone tissue inside the callus. Vitamin K2 administration to GCuntreated rats decreased the osteoclast surface/bone surface (OcS/BS), osteoblast surface (ObS)/BS, eroded surface (ES)/BS, and bone formation rate (BFR)/BS and increased the lamellar area/bone area. Although GC treatment increased the ES/BS and decreased the ObS/BS, BFR/BS, and lamellar area/bone area, vitamin K2 administration to GC-treated rats decreased the OcS/BS and prevented an increase in the ES/BS and a decrease in the lamellar area/ bone area. These results suggested that vitamin K2 downregulated bone turnover and stimulated lamellar bone formation in GC-untreated rats and prevented an increase in bone resorption while maintaining bone formation and prevented a decrease in lamellar bone formation in GCtreated rats. Thus, vitamin K2 appears to be effective for promoting bone healing in a rat femoral osteotomy model with or without GC treatment. © Springer Science+Business Media, LLC 2010.


Yamamoto D.,Nagoya University | Iida T.,Nagoya University | Kuroda K.,Nagoya University | Ichino R.,EcoTopia Science Institute | And 2 more authors.
Materials Transactions | Year: 2012

Anodizing of Ti specimens were performed in concentrated H 3PO 4 aqueous solutions with a purpose to incorporate a large amount of phosphate ion into anodized coatings, and their osteoconductivity was evaluated in in vivo test. Ti specimens were anodized in 0.1-11M H 3PO 4 aqueous solutions up to 200V at a rate of 0.1Vs -1. Anodized coatings were evaluated with SEM, TEM, XRD, XPS, and laser microscope. Anodized specimens were implanted in rats' tibia for 14 d, and then extracted. When anodized in concentrated (≥2M) H 3PO 4 aqueous solutions under spark discharge, crystallized anatase transformed to amorphous anatase by containing a large amount of PO 4 3- in crystal lattice of TiO 2. The amorphous anatase coatings had better osteoconductivity than the crystallized anatase coatings. It is not exactly clear what was the intrinsic factor for the high osteoconductivity, but the crystallinity of anatase and/or PO 4 3- in the film is considered to be responsible for the difference in bone-forming ability of TiO 2 films. © 2012 The Japan Institute of Metals.


Yamamoto D.,Nagoya University | Kawai I.,Nagoya University | Kuroda K.,Nagoya University | Ichino R.,EcoTopia Science Institute | And 2 more authors.
Materials Transactions | Year: 2011

The aim of this study was to elucidate the relationship between the surface roughness and osteoconductivity of anodized titanium surfaces. Before anodizing, titanium substrates with different surface roughness were prepared by wet-polishing. These substrates were anodized at various voltages in H 3PO 4, H 2SO 4, and NaOH aqueous solutions, and their surface roughness was controlled simultaneously at the micron level. Surface roughness of these coatings was expressed with the arithmetical means (Ra). The osteoconductivity of anodized samples was evaluated by in vivo tests. In in vivo tests, samples were implanted in rats' tibia for 14 d. Anatase type TiO 2 films were formed on all of the anodized samples for in vivo tests. It was newly found that TiO 2 film with small Ra value exhibited high osteoconductivity than that with high Ra value, especially when Ra value was <0:3 μm. In addition, the osteoconductivity of anodized samples with Ra/μm > 0:3 was not improved by anodizing, showing the same low osteoconductivity of as-polished samples. These tendencies were observed for all of the TiO 2 films regardless of the type of electrolytes. © 2011 The Japan Institute of Metals.


Iwamoto J.,Keiyu Orthopaedic Hospital | Seki A.,Hamri Co. | Nango N.,Ratoc System Engineering Co.
Calcified Tissue International | Year: 2016

Teriparatide (TPTD) is known to increase the cortical thickness and porosity. The purpose of the present study was to determine whether switching from TPTD to ibandronate (IBN) would be useful for improving cortical bone parameters as assessed using high-resolution quantitative computed tomography (HR-QCT) analyses in mature rabbits. Forty-two female New Zealand white rabbits (18–22 weeks old) were randomized into six groups of 7 animals each as follows: 4-week vehicle administration group, 4-week TPTD administration group (20 μg/kg, subcutaneously [s.c.], daily), 12-week vehicle administration group, 4-week TPTD administration + 8-week vehicle administration group, 4-week TPTD administration + 8-week lower-dose IBN administration group (20 μg/kg, s.c., every 4 weeks), and 4-week TPTD administration + 8-week higher-dose IBN administration group (100 μg/kg, s.c., every 4 weeks). After the 4- or 12-week experimental period, the cortical bone of the distal femoral diaphysis was processed for HR-QCT analysis. The 4-week TPTD administration increased the pore ratio, number, and density as well as the cortical area, thickness, and bone mineral content (BMC), without significant influencing the volumetric bone mineral density (BMD). The 4-week TPTD administration + 8-week vehicle administration decreased the pore ratio, number, and density as well as the cortical area and thickness, compared with the 4-week TPTD administration, but the pore ratio, cortical area, and thickness were still higher compared with the 12-week vehicle administration. The 4-week TPTD administration + 8-week higher-dose IBN administration, but not the 4-week TPTD administration + 8-week lower-dose IBN administration, increased the cortical area, thickness, BMC, and volumetric BMD and decreased the pore ratio, but not the pore number or density, compared with the 4-week TPTD administration + 8-week vehicle administration. These results suggest that higher-dose IBN after TPTD therapy has a beneficial effect on the BMC, volumetric BMD, cortical area, thickness, and porosity in mature rabbits. © 2016 Springer Science+Business Media New York


This study investigated the effects of combined teriparatide (an anabolic agent) and monthly risedronate (an anti-resorptive agent) therapy on cancellous bone mass in orchidectomized (ORX) rats. Fifty 14-week-old male Sprague–Dawley rats were randomized into five groups of ten animals each: sham-operation + vehicle; ORX + vehicle; ORX + risedronate (90 μg/kg subcutaneous, every 4 weeks); ORX + teriparatide (30 μg/kg subcutaneous, three times per week); and ORX + risedronate + teriparatide. After the 12-week experimental period, cancellous bone in the tibial proximal metaphysis was examined by static and dynamic histomorphometric analyses. ORX decreased bone volume per total volume (BV/TV) and trabecular number (Tb.N), and increased trabecular separation (Tb.Sp). Risedronate increased BV/TV and Tb.N above the sham control values, while teriparatide prevented the ORX-induced decrease in BV/TV and increased trabecular width (Tb.Wi) above sham control levels. Risedronate decreased Tb.Sp below control values, while teriparatide prevented the ORX-induced increase in Tb.Sp. The combination of teriparatide and risedronate further increased BV/TV and Tb.N and decreased Tb.Sp as a result of suppression of bone remodeling, compared with teriparatide alone. These results suggest that teriparatide and monthly risedronate exert different effects on cancellous bone structure and thus have additive effects on cancellous bone mass in ORX rats. © 2015, Springer Science+Business Media New York.


Iwamoto J.,Keio University | Seki A.,Hamri Co. | Sato Y.,Mitate Hospital | Matsumoto H.,Keio University | And 2 more authors.
Calcified Tissue International | Year: 2011

The purpose of the present study was to examine the effect of vitamin K2 on cancellous and cortical bone mass in rats with streptozotocin (STZ)-induced type 1 diabetes. Twenty-seven male Sprague-Dawley rats aged 12 weeks were randomized by the weight-stratified method into the following three groups: age-matched control group, STZ + vehicle group, and STZ + vitamin K 2 group. STZ (40 + 50 mg/kg) was administered intravenously twice during the initial 1-week period. Vitamin K2 (menatetrenone, 30 mg/kg) was administered orally 5 days a week. After 12 weeks of treatment, the serum glucose concentration and femoral length and weight were measured and histomorphometric analysis was performed on the cancellous and cortical bone of the distal femoral metaphysis and femoral diaphysis, respectively. STZ administration induced hyperglycemia and a decrease in femoral weight. The STZ + vehicle group also showed cancellous osteopenia due to a decrease in the number of osteoblasts/bone surface (N.Ob/BS) and the osteoblast surface (ObS)/BS without any significant changes in boneresorption parameters, but it did not have a significant decrease in cortical bone mass. Administration of vitamin K2 to STZ-treated rats prevented the development of hyperglycemia and a decrease in femoral weight. Vitamin K2 also prevented cancellous osteopenia by inhibiting the decrease in N.Ob/BS and ObS/BS without significantly affecting bone-resorption parameters, but it did not significantly increase cortical bone mass. These results suggest that vitamin K2 has beneficial effects on glucose concentration and cancellous bone mass in rats with STZ-induced type 1 diabetes. © Springer Science+Business Media, LLC 2010.

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