Nihon Bioresearch Inc
Nihon Bioresearch Inc
Sakai H.,Waseda University |
Sakai H.,Waseda Bioscience Research Institute in Singapore |
Suzuki Y.,Nihon Bioresearch Inc. |
Sou K.,Waseda University |
Kano M.,Nihon Bioresearch Inc.
Journal of Biomedical Materials Research - Part A | Year: 2012
Intravenous injection of liposomes into pigs reportedly induces anaphylactoid reactions at a small dose, resulting in circulatory disorder. Hemoglobin vesicles (HbVs) are artificial oxygen carriers encapsulating Hb solution in liposomes. It is not known how pigs respond to HbV injection. We aimed to analyze the cardiopulmonary responses to small injections of HbV and empty vesicle (EV) and compare them with a conventional liposome (CL) with a different lipid composition containing phosphatidylglycerol (PG). PG is known to induce an anaphylactoid reaction in pigs. Nine male miniature pigs were used for HbV, EV, and CL injections. The anesthetized pig received 0.05 and 0.5 mL/kg of a test fluid for the first and second injection with a 70 min interval. Results show that CL repeatedly induced significant increases in systemic and pulmonary arterial pressures and vascular resistances and decreases in heart rate and cardiac output (CO). HbV and EV at the first injection-induced pulmonary hypertension, with significantly smaller changes in systemic arterial pressure and CO. No remarkable response was visible at the second injection in spite of a larger dosage. Only CL repeatedly induced thrombocytopenia, leukocytopenia, and plasma thromboxane B2 increase resulting from complement activation, although HbV and EV showed smaller changes. Transmittance electron micrograph of pulmonary intravascular macrophages (PIMs) showed phagocytosis of HbV, indicating the possibility that nonspecific phagocytosis by PIMs relates to the responses observed after the first injection. HbV does not induce a significant anaphylactoid reaction in pigs compared with CL because of the different lipid composition. © 2012 Wiley Periodicals, Inc.
Takahashi K.,National Institute of Mental Health |
Murasawa H.,Nihon Bioresearch Inc. |
Yamaguchi K.,Nihon Bioresearch Inc. |
Yamada M.,National Institute of Mental Health |
And 5 more authors.
Behavioural Brain Research | Year: 2011
Growing evidence indicates that the glutamatergic neurotransmitter system is central to the neurobiology and treatment of depression. Riluzole, a drug currently used to slow the progression of amyotrophic lateral sclerosis (ALS), directly affects the glutamatergic system. In this study, we investigated the effects of riluzole in olfactory bulbectomy (OBX) rats, an animal model of depression. The olfactory bulbs in rats were removed by suction. The emotionality of rats was measured by scoring their responses to given stimuli, i.e., attack, startle, struggle, and fight responses. The OBX rats chronically treated with vehicle for 7 days at 14 days following surgery showed significant increases in emotionality responses. Single (1st day administration) and subchronic (7th day administration) riluzole treatment (1-10. mg/kg, po) significantly and dose-dependently reduced hyperemotional responses in OBX rats. Both single and subchronic riluzole treatment (10. mg/kg, po) had no significant effects on the emotional responses in sham operated rats. In addition, we demonstrated that single riluzole treatment (10. mg/kg, po) significantly decreased extracellular glutamate levels in medial prefrontal cortex of OBX rats by in vivo microdialysis. We provide the first experimental evidence that riluzole rapidly attenuated hyperemotional responses in OBX rats, an animal model of depression. © 2010 Elsevier B.V.
Hirasawa Y.,Meijo University |
Hirasawa Y.,Nihon Bioresearch Inc. |
Sakai T.,Meijo University |
Ito M.,Meijo University |
And 3 more authors.
European Journal of Pharmacology | Year: 2011
Hyperglycemia and hyperlipidemia are considered critical to the development of diabetic nephropathy. The aim of this study is to clarify the effect of cholesterol on advanced-glycation-end-products and the mechanisms behind the advanced-glycation-end-product-cholesterol-aggregated bovine serum albumin (BSA)-induced proliferation of mesangial cells. Mesangial cells were treated with advanced-glycation-end-product-cholesterol-aggregated-BSA, and RNA and protein were isolated. Cholesterol caused a 1.5-fold increase in fluorescent intensity and 2-fold increase in advanced-glycation-end-products in vitro. Pyridoxamine, aminoguanidine, and N-acetyl-l-cycteine suppressed the production of advanced-glycation-end-product-cholesterol-aggregated-BSA. Advanced-glycation-end-product-cholesterol-BSA was analyzed by matrix-assisted-laser-desorption/ionization-time of flight mass spectrometry, and peaks were found to shift toward a higher mass. Advanced-glycation-end- product-cholesterol-aggregated-BSA induced overexpression of the mRNA of transforming growth factor-beta1, collagen type 1, collagen type 4 and receptor for advanced-glycation-end-products, and the proliferation of mesangial cells. The injection of advanced-glycation-end-product-cholesterol-aggregated-BSA caused glomerular changes and albuminuria in non-diabetic mice. A transforming-growth-factor-beta receptor1 kinase inhibitor or Mitogen-activated-Protein-Kinase/Extracellular-Signal-regulated-Kinase kinase (ERK) inhibitor (U-0126) suppressed the proliferation of mesangial cells induced by advanced-glycation-end-product-cholesterol-aggregated-BSA dose-dependently. U-0126 inhibited the phosphorylation of ERK1/2 in advanced-glycation-end- product-cholesterol-aggregated-BSA treated mesangial cells. These findings suggested that cholesterol promotes the formation of advanced-glycation-end- products-protein and that advanced-glycation-end-product-cholesterol-aggregated protein stimulates mesangial cells to proliferate via transforming-growth- factor-beta receptors and the ERK-MAPK pathway in diabetic glomeruli. © 2011 Elsevier B.V. All rights reserved.
Ohata A.,Otsuka Pharmaceutical Factory Inc. |
Tamura N.,Otsuka Pharmaceutical Factory Inc. |
Iwata K.,Otsuka Pharmaceutical Factory Inc. |
Abe N.,Otsuka Pharmaceutical Factory Inc. |
And 4 more authors.
Journal of Surgical Research | Year: 2014
Background Preventing interbowel adhesions still remains a challenge. Peritoneal mesothelial damage can induce postoperative adhesions. Our study evaluated the effects of 3% trehalose solution on mesothelial protection and adhesion prevention. Also, we compared this novel solution with Seprafilm regarding efficacy. Methods Mesothelial damage was induced on the cultured human mesothelial cell (Met-5A) and rabbit cecum-serosal surface by air-drying for 60 min, and trehalose solution was applied. Cell integrity was tested by measuring lactate dehydrogenase, and serosal-morphologic changes were analyzed using scanning electron microscopy. Intra-abdominal adhesions were induced in rabbits by the combination of abrasion and air-drying procedures. Animals were divided into four groups: control, 3% trehalose solution, Seprafilm, and 3% trehalose solution with Seprafilm. Adhesions were evaluated blindly 7 d later. Results Lactate dehydrogenase release from the Met-5A cells was reduced dose-dependently by trehalose (P < 0.05). Morphologic studies clearly showed that mesothelial cells on the serosal surface were kept intact by 3% trehalose solution. In a rabbit adhesion model, 3% trehalose solution reduced adhesions between bowel and bowel or bowel and surrounding structures (P < 0.01 versus control and Seprafilm). Seprafilm reduced adhesions between abdominal wall and underlying viscera (P < 0.01 versus control and 3% trehalose solution). Three-percent trehalose solution with Seprafilm showed additive effects of adhesion prevention, reducing adhesion formation at the previously mentioned sites. Conclusions Three-percent trehalose solution protects mesothelial cells and leads to reduced adhesions between bowel and bowel or bowel and surrounding structures. This effect seems to be resulted from the characteristics of the solution covering most areas that potentially develop adhesions. © 2014 Elsevier Inc. All rights reserved.
Yoshimura M.,Kikkoman Corporation |
Toyoshi T.,Nihon Bioresearch Inc. |
Sano A.,Kikkoman Corporation |
Izumi T.,Kikkoman Corporation |
And 7 more authors.
Journal of Agricultural and Food Chemistry | Year: 2010
This study aimed to investigate the effects of a γ-aminobutyric acid (GABA) rich tomato (Solanum lycopersicum L.) cultivar 'DG03-9' in comparison with 'Momotaro', a commonly consumed tomato cultivar in Japan, on systolic blood pressure (SBP) in spontaneously hypertensive rats (SHR). In a single administration study, treatment with the GABA-rich cultivar elicited a significant decrease in SBP compared to the control group. In a chronic administration study, SHR were fed diets containing one of the tomato cultivars for 4 weeks. Both cultivars significantly reduced the increase In SBP compared to the control. The antihypertensive effect of the GABA-rich cultivar was higher than that of the commonly consumed cultivar in both the single- and chronic-administration studies. Treatment with a comparable amount of GABA elicited a similar response to treatment with the GABA-rich cultivar. These results suggest that the GABA-rich cultivar 'DG03-9' is a potent antihypertensive food and may be useful for treating hypertension effectively. © 2009 American Chemical Society.
Kasai S.,Eisai Co. |
Ito A.,Ito Bone Histomorphometry Institute |
Shindo K.,Canon Inc. |
Toyoshi T.,Nihon Bioresearch Inc. |
Bando M.,Eisai Co.
PLoS ONE | Year: 2015
Oxidative stress affects bone turnover. Preventative effects of antioxidants such as vitamin E on reduced bone mineral density and fractures associated with aging, osteoporosis, and smoking have been examined in animals and humans. The effects of vitamin E (α-tocopherol; αT) on bone health have yielded conflicting and inconclusive results from animal studies. In this study, to determine the bone effects of αT, we investigated the in vivo effects of αT on the bone mineral density, bone mass, bone microstructure, bone resorption, and osteogenesis through peripheral quantitative computed tomography (pQCT) measurements, micro-computed tomography (micro-CT) analyses, and bone histomorphometry of lumbar vertebrae and femurs in normal female Wistar rats fed diets containing αT in different quantities (0, 30, 120, or 600 mg/kg diet) for 8 weeks. To validate our hypotheses regarding bone changes, we examined ovariectomized rats as an osteoporosis model and control sham-operated rats in parallel. As expected, ovariectomized rats had reduced bone mineral density in lumbar vertebrae and the distal metaphyses of their femurs, reduced bone mass and deteriorated microstructure of cancellous bones in the vertebral body and distal femur metaphyses, and reduced bone mass due to resorption-dominant enhanced bone turnover in secondary cancellous bones in these sites. In comparison, αT administered to normal rats, even at the highest dose, did not induce reduced bone mineral density of lumbar vertebrae and femurs or a reduced bone mass or fragile microstructure of cancellous bones of the vertebral body and distal femur metaphyses. Instead, αT-fed rats showed a tendency for an osteogenesis-dominant bone mass increase in secondary cancellous bones in the vertebral body, in which active bone remodeling occurs. Thus, αT consumption may have beneficial effects on bone health. © 2015 Kasai et al.
Matsui Y.,Nihon Bioresearch Inc |
Matsui Y.,Meijo University |
Hirasawa Y.,Nihon Bioresearch Inc |
Sugiura T.,Nihon Bioresearch Inc |
And 3 more authors.
Biological and Pharmaceutical Bulletin | Year: 2010
In an acute treatment experiment, metformin (150, 300 mg/kg, per os (p.o.)) markedly reduced the consumption of a high-fat diet (HFD) (45 kcal% fat-containing diet) for 2 h after the HFD was given to the fasted male C57BL/6J (B6) mice. In addition, metformin at a higher dose increased plasma active glucagon-like peptide-1 (GLP-1) levels at 1h after the HFD was given. On the other hand, pioglitazone (12 mg/kg,p.o.) slightly increased the food intake but did not affect active GLP-1 levels when given at 6 and 12 mg/kg, p.o. In a long-team experiment for 9 weeks, metformin treatment (0.25, 0.5% in the HFD) resulted in reduction of body weight gain and HFD intake. When wet weights of various body fat pads of each mouse were measured at 9 weeks after treatment, metformin markedly decreased these weights. However, pioglitazone treatment (0.01, 0.02% in the HFD) did not have obvious effects on these parameters. Oral glucose tolerance test was carried out after 20-h fasting at 4 weeks post-treatment. Whereas metformin treatment (0.25, 0.5%) markedly improved glucose intolerance, pi-oglitazone treatment (0.02%) slightly improved this parameter. At 9 weeks, both metformin and pioglitazone markedly improved hyperglycemia and hyperinsulinemia. Metformin treatment also improved hyperleptinemia, whereas pioglitazone was ineffective. These results indicate that metformin reduces body weight gain and improves glucose intolerance in HFD-induced obese diabetic B6 mice. © 2010 Pharmaceutical Society of Japan.
Takakura S.,Astellas Pharma Inc. |
Toyoshi T.,Nihon Bioresearch Inc. |
Hayashizaki Y.,Astellas Pharma Inc. |
Takasu T.,Astellas Pharma Inc.
Life Sciences | Year: 2016
Aims We investigated the effect of the selective sodium-dependent glucose cotransporter 2 inhibitor ipragliflozin on the simultaneous progression of diabetic microvascular complications of retinopathy, nephropathy and neuropathy in individual Spontaneously Diabetic Torii (SDT) fatty rats. Main methods Ipragliflozin was administered to male SDT fatty rats for 12 weeks. Male Sprague-Dawley rats of the same age were used as non-diabetic controls. Non-fasting plasma glucose and glycated hemoglobin levels were measured every 4 weeks. Cataract formation was monitored once a week, and the electroretinogram was measured after 6 weeks of treatment. After the treatment period, motor nerve conduction velocity was measured and urinalysis was conducted. Tissue samples were then dissected for histopathological examination. Key findings Treatment with ipragliflozin reduced glycated hemoglobin levels, inhibited the progression of cataract formation, prevented the prolongation of oscillatory potential peaks in the electroretinogram, ameliorated the slowing of motor nerve conduction velocity, and reduced the severity of glomerulosclerosis in SDT fatty rats. Significance These results suggest that the control of hyperglycemia with ipragliflozin slows the progression of the diabetic complications of retinopathy, nephropathy, and neuropathy. © 2016 Elsevier Inc. All rights reserved.
PubMed | Nihon Bioresearch Inc. and Astellas Pharma Inc.
Type: | Journal: Life sciences | Year: 2016
We investigated the effect of the selective sodium-dependent glucose cotransporter 2 inhibitor ipragliflozin on the simultaneous progression of diabetic microvascular complications of retinopathy, nephropathy and neuropathy in individual Spontaneously Diabetic Torii (SDT) fatty rats.Ipragliflozin was administered to male SDT fatty rats for 12weeks. Male Sprague-Dawley rats of the same age were used as non-diabetic controls. Non-fasting plasma glucose and glycated hemoglobin levels were measured every 4weeks. Cataract formation was monitored once a week, and the electroretinogram was measured after 6weeks of treatment. After the treatment period, motor nerve conduction velocity was measured and urinalysis was conducted. Tissue samples were then dissected for histopathological examination.Treatment with ipragliflozin reduced glycated hemoglobin levels, inhibited the progression of cataract formation, prevented the prolongation of oscillatory potential peaks in the electroretinogram, ameliorated the slowing of motor nerve conduction velocity, and reduced the severity of glomerulosclerosis in SDT fatty rats.These results suggest that the control of hyperglycemia with ipragliflozin slows the progression of the diabetic complications of retinopathy, nephropathy, and neuropathy.
PubMed | Nihon Bioresearch Inc.
Type: Journal Article | Journal: The Journal of toxicological sciences | Year: 2016
The body surface area (BSA) of an organism is an important parameter for evaluating physiological functions. In drug development, normalization by BSA is an appropriate method for extrapolating doses between species. The BSA of animals has generally been estimated by multiplying a constant by the power of the body weight (BW). Recently, the use of miniature pigs in non-clinical studies for medical drugs or devices has gradually been increasing. However, verification of their BSA is not as yet sufficient. In this study, we measured the BSAs of 40 laboratory miniature pigs (11 males and 9 females of Gttingen minipig and 14 males and 6 females of Nippon Institute for Biological Science [NIBS] miniature pig) by analyzing computed tomography (CT) images, since measurements using a CT scanner were expected to more precisely determine BSA than classical measuring techniques. The measurement results showed the BSAs of the 20 Gttingen minipigs to range from 0.4358 to 0.8356 m(2) (the working BW range: 12.7-37.0 kg) and 20 NIBS miniature pigs to range from 0.2906 to 0.8675 m(2) (the working BW range: 7.9-41.5 kg). Since accuracy and reproducibility were confirmed by measuring the surface area of an acrylic cuboid, we concluded the measurement method employed in this study to be very reliable. We propose the following estimating formula for BSA of laboratory miniature pigs: 100 BSA [m(2)] = 7.98 BW [kg](2/3).