Takenori Yamashita

Drinking hydrogen water ameliorated cognitive impairment in senescence-accelerated mice.

Hydrogen has been reported to have neuron protective effects due to its antioxidant properties, but the effects of hydrogen on cognitive impairment due to senescence-related brain alterations and the underlying mechanisms have not been characterized. In this study, we investigated the efficacies of drinking hydrogen water for prevention of spatial memory decline and age-related brain alterations using senescence-accelerated prone mouse 8 (SAMP8), which exhibits early aging syndromes including declining learning ability and memory. However, treatment with hydrogen water for 30 days prevented age-related declines in cognitive ability seen in SAMP8 as assessed by a water maze test and was associated with increased brain serotonin levels and elevated serum antioxidant activity. In addition, drinking hydrogen water for 18 weeks inhibited neurodegeneration in hippocampus, while marked loss of neurons was noted in control, aged brains of mice receiving regular water. On the basis of our results, hydrogen water merits further investigation for possible therapeutic/preventative use for age-related cognitive disorders.

Adolescent exercise associated with long-term superior measures of bone geometry: a cross-sectional DXA and MRI study

Objective: To investigate whether childhood sports participation, particularly weight-bearing sports, has any effect on bone mineral content (BMC), areal bone mineral density (aBMD) and bone geometric characteristics in middle-aged postmenopausal women. Design/setting: In this cross-sectional comparison of two groups, 46 middle-aged women (mean age, 60.2 (SD 5.6) years; range, 52–73 years) were grouped according to sport participation during growth: weight-bearing sports, including high-impact weight-bearing activities; and low-impact non-weight-bearing sports or no participation. Main outcome measures: Dual energy X-ray absorptiometry (DXA)-measured BMC, aBMD in the lumbar spine and femur. Magnetic resonance imaging (MRI) determined bone geometric characteristics in the femur, such as femoral mid-diaphyseal cross-sectional area, periosteal and endosteal perimeters and maximum and minimum second moment of area. Results: Postmenopausal middle-aged women with participation in weight-bearing sports during junior high to high school (12–18 years old) displayed significantly greater BMC in both lumbar spine and femoral neck regions, and also significantly greater femoral mid-diaphyseal bone cross-sectional area, periosteal perimeter and maximum and minimum second moment of area than the non-weight-bearing sports group. Conclusions: Adolescent weight-bearing exercise exerts preservational effects on femoral mid-diaphyseal size and shape, while DXA-measured BMC effectively identified the same tendency. Weight-bearing exercise in youth affects bone, and these effects may be preserved as BMC, geometric and structural advantages even after 40 years.

Immune Activation and Radioprotection by Propolis

In this study, we focused on immune stimulation by Propolis, and examined changes in the effect of irradiation after Propolis administration. We also examined the radioprotective effect of Propolis by observing its effect on the immune system. The effect of immune activation by Propolis was investigated by measuring the total immunoglobulin (Ig) G and IgM. The radioprotective effect of immune activation by Propolis was investigated by measuring the T-lymphocyte subsets in the peripheral blood of mice following whole body irradiation. Compared with the control group, the IgG was significantly reduced in the Propolis group, indicating that Propolis suppressed IgG production. ELISA revealed that the amount of IgM in mouse serum was significantly higher in the Propolis group as compared with the control group, indicating that Propolis increased IgM production. The number of CD4-positive cells was increased only in the Propolis group. Likewise, the number of CD4-positive cells increased by 81% in the Propolis with irradiation group compared with the irradiation group alone. Compared with the control group, the Propolis group increased CD8-positive cells. Compared with the irradiation alone group, CD8-positive cells were decreased by Propolis with irradiation group. Propolis activated macrophages to stimulate interferon (IFN)-gamma production in association with the secondary activation of T-lymphocytes, resulting in a decrease in IgG and IgM production. Cytokines released from macrophages in mouse peripheral blood after Propolis administration activated helper T-cells to proliferate. In addition, activated macrophages in association with the secondary T-lymphocyte activation increased IFN-gamma production and stimulated proliferation of cytotoxic T-cells and suppressor T-cells, indicating the activation of cell-mediated immune responses.

Taurine Administration Mitigates Cisplatin Induced Acute Nephrotoxicity by Decreasing DNA Damage and Inflammation: An Immunocytochemical Study

Cisplatin (CDDP) is one of the most effective chemotherapeutic agent used in the treatment of many kind of solid tumors. Its primary side effect is nephrotoxicity. The aim of this study to investigate the effects of taurine on cisplatin-induced acute nephrotoxicity. A single intraperitoneal injection of CDDP (15 mg/kg, or 25 mg/kg) deteriorated the kidney functions as reflected by histopathological changes. Histopathological changes were observed in all cisplatin groups. In the cisplatin group, oxidative stress was evident in the cisplatin group by observing an increase in 8-OHdG expression, an indicator of oxidative DNA damage. CDDP also resulted to an increase in CD68 expression in the renal tissues of CDDP groups. Taurine transporter (TauT) was down-regulated, and p53 was up-regulated in renal tissues as indicated by immunohistochemical analysis. Administration with taurine prior to a cisplatin injection was able to protect against deterioration of kidney function, to abrogate the decline in anti-oxidants and to suppress the increase in DNA damage. Moreover, taurine inhibited p53 activation and improved the pathological changes induced by cisplatin. This study demonstrates the protective effects of taurine in attenuating the expression of pro-inflammatory mediators and in improving antioxidant capacity in the kidney of cisplatin-injected rats. Thus, taurine could be a beneficial dietary supplement to attenuate cisplatin induced nephrotoxicity.

Effect of Taurine on iNOS-Mediated DNA Damage in Drug-Induced Renal Injury.

Owing to an outstanding wide antitumor spectrum and excellent anti-tumor effect cisplatin has been used in chemotherapy for malignant tumor. However, cisplatin has strong side effects such as renal injury. Taurine has been found to protect against inflammatory tissue damage in a variety of experimental models. The aim of the present study was to investigate the effect of taurine against iNOS dependent DNA damage in cisplatin-induced renal injury in rats. With the help of a rat model of drug-induced kidney damage, we have assessed the nephrotoxic effects of different doses of cisplatin in the presence and absence of taurine. Immunohistochemical methods were used to examine the distribution of arginine, iNOS, citrulline and 8-nitroguanine in renal tissue. The expression levels of citrulline, iNOS, and 8-nitroguanine immunoreactivities were found to increase as a function of the dose of cisplatin used, and to decrease in the presence of taurine. The expression level of arginine immunoreactivity was reduced as a function of the dose of cisplatin used. On the other hand, iNOS, 8-nitroguanine and citrulline immunohistochemical staining showed an intense immunoreactivity in the renal tubule of cisplatin-treated animals; and arginine immunoreactivity was localized in the renal tubule of taurine-treated animals. We also confirmed the decrease of citrulline and iNOS expression in the renal tubule after taurine administration as well as the expression level of 8-nitroguanine, a nitrative stress marker in the same animals. The present results support the concept that taurine may have a protective role in the formation of cisplatin-related DNA lesions arising through iNOS-mediated nitrative stress.

Characteristics of bone strength and metabolism in type 2 diabetic model Tsumura, Suzuki, Obese Diabetes mice

Objective Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by hyperglycemia, hyperinsulinemia, and complications such as obesity and osteoporosis. The Tsumura, Suzuki, Obese Diabetes (TSOD) mouse is an animal model of spontaneous obese T2DM. However, bone metabolism in TSOD mice is yet to be investigated. The objective of the present study was to investigate the effects of T2DM on bone mass, metabolism, microstructure, and strength in TSOD mice. Methods We determined the following parameters in TSOD mice and Tsumura, Suzuki, Non-obesity (TSNO) mice (as controls): serum glucose levels; serum insulin levels; bone mass; bone microstructure; bone metabolic markers; and bone strength. We also performed the oral glucose tolerance test and examined histological sections of the femur. We compared these data between both groups at pre-diabetic (10 weeks) and established (20 weeks) diabetic conditions. Results Bone strength, such as extrinsic mechanical properties, increased with age in the TSOD mice and intrinsic material properties decreased at both 10 weeks and 20 weeks. Bone resorption marker levels in TSOD mice were significantly higher than those in the control mice at both ages, but there was no significant difference in bone formation markers between the groups. Bone mass in TSOD mice was lower than that in controls at both ages. The trabecular bone volume at the femoral greater trochanter increased with age in the TSOD mice. The femoral mid-diaphysis in TSOD mice was more slender and thicker than that in TSNO mice at both ages. Conclusions Bone mass of the femur was lower in TSOD mice than in TSNO mice because hyperinsulinemia during pre-diabetic and established diabetic conditions enhanced bone resorption due to high bone turnover. In addition, our data suggest that the bone mass of the femur was significantly reduced as a result of chronic hyperglycemia during established diabetic conditions in TSOD mice. We suggest that bone strength in the femur deteriorated due to the reduction of bone mass and because the femoral mid-diaphysis was more slender in TSOD mice.

Characteristics of Bone Strength and Metabolism in Type 2 Diabetic Model Nagoya Shibata Yasuda Mice

We evaluated the suitability of Nagoya Shibata Yasuda (NSY) mice as an animal model for examining the influence of a glucose metabolism disorder on bone integrity, using Institute of Cancer Research (ICR) mice as controls. We selected six NSY and ICR mice each that were matched for weight, and measured serum glucose levels, serum insulin levels, and conducted an oral glucose tolerance test. Histological sections of the femurs of both mouse lines were prepared, and the bone strength, mass, and microstructure of the femur were compared, along with bone metabolism. Serum glucose levels were significantly higher in the NSY mice than in the control mice, but body weight and serum insulin levels did not differ between the groups. Bone mass, microstructure, and strength of the femur, and bone metabolism were lower in the NSY mice than in the control mice. In the cortical bone of the femur in the NSY mice, several parts were not stained with eosin, demonstrating a strong negative correlation between serum glucose levels and bone mineral density; however, there was a negative correlation between serum glucose levels and bone metabolic markers. The bone turnover rate in the NSY mice was decreased by hyperglycemia, resulting in a thinner and shorter femur, reduced cortical and trabecular areas, and lower bone mass compared to those of the control mice. Collectively, these results suggest deteriorated bone strength of the femur in NSY mice, serving as a useful model for studying the link between glucose metabolism and bone integrity.

Effect of Radiation on the Expression of Taurine Transporter in the Intestine of Mouse

There has been a growing interest on the effects of radiation since the Fukushima nuclear power plant accident of 2011. Taurine has been reported to have a radioprotective effect in irradiated mice. However, the detailed mechanism of this radioprotective effect is still awaiting clarification. The aim of this study was to investigation how radiation affects the expression of taurine and to shed light on the mechanism accounting for radioprotective and radiation mitigating effect. Six-week-old male mice were randomly divided into two groups: IR group (7 Gy irradiation) and IR + Tau group (7 Gy irradiation + taurine 3000 mg/kg/day). We examined the survival rate, the expression of taurine and taurine transporter in the small intestine and the urinary taurine concentration. In this study, no statistically significant difference was found in the survival rate between IR Group and IR + Tau Group. Three days and 7 days after irradiation, the urinary taurine concentration of IR + Tau group increased more than that of IR group. Three days and 10 days after irradiation, the expression of taurine and taurine transporter in the small intestine of IR group and IR + Tau group decreased more than that of normal small intestine. It is reported that radiation exposure increases the urinary taurine concentration. We found that the radiation exposure decreases the expression of the taurine transporter in the small intestine of mouse. This finding suggests that a decrease in the expression of the taurine transporter promotes the release of taurine from the tissue into the urine.

Pharmaceutical Production of Anti-tumor and Immune-potentiating Enterococcus faecalis-2001 β-glucans: Enhanced Activity of Macrophage and Lymphocytes in Tumor-implanted Mice

BACKGROUND Enterococcus faecalis 2001 is a probiotic lactic acid bacterium and has been used as a biological response modifier (BRM). From physiological limitation of bacterial preservation in storage and safety, the live E. faecalis 2001 has been heat-treated and the BRM components containing high level of β-glucan, named EF-2001, were prepared. METHOD The heat-treated EF-2001 has been examined for the antioxidative potential for radical scavenging and anti-tumor activities as well as immune-enhancing response in mice. Lymphocyte versus polymorphonuclear leukocyte ratio was increased in mice upon treatment with EF-2001. The number of lymphocytes was increased in the EF-2001-treated group. In the mice bearing two different Ehrlich solid and Sarcoma-180 carcinomas, the treatment with EF-2001 resulted in anti-tumor action. Tumor-suppressive capacity upon treatment with EF-2001 was significantly increased compared to normal controls. RESULTS During the time interval administration of 5 weeks between the priming and secondary administration of EF-2001, the expression and production levels of TNF-α were also observed in the EF- 2001-administered mice. Additionally, anti-tumor activity examined with the intravenous administration of EF 2001 with a 34 times interval was also observed, as the growth of Sarcoma180 cells was clearly inhibited by the EF-2001. CONCLUSION From the results, it was suggested that the immune response is enhanced due to antioxidative activity caused by the EF-2001 and anti-tumor activity by NK cells and TNF-α.

Effect of low‐repetition jump training on bone mineral density in young women

The hypothesis of the present study was that low‐repetition and high‐impact training of 10 maximum vertical jumps/day, 3 times/week would be effective for improving bone mineral density (BMD) in ordinary young women. Thirty‐six female college students, with mean age, height, and weight of 20.7±0.7 years, 158.9±4.6 cm, and 50.4±5.5 kg, respectively, were randomly divided into two groups: jump training and a control group. After 6 months of maximum vertical jumping exercise intervention, BMD in the femoral neck region significantly increased in the jump group from the baseline (0.984±0.081 vs 1.010±0.080 mg/cm2; P<0.01), although there was no significant change in the control group (0.985±0.0143 vs 0.974±0.134 mg/cm2). And also lumbar spine (L(2–4)) BMD significantly increased in the jump training group from the baseline (0.991±0.115 vs 1.015±0.113 mg/cm2; P<0.01), whereas no significant change was observed in the control group (1.007±0.113 vs 1.013±0.110 mg/cm2). No significant interactions were observed at other measurement sites, Wards triangle, greater trochanter, and total hip BMD. Calcium intakes and accelometry‐determined physical daily activity showed no significant difference between the two groups. From the results of the present study, low‐repetition and high‐impact jumps enhanced BMD at the specific bone sites in young women who had almost reached the age of peak bone mass.