The combination therapy with alfacalcidol and risedronate improves the mechanical property in lumbar spine by affecting the material properties in an ovariectomized rat model of osteoporosis

<p>Abstract</p> <p>Background</p> <p>We conducted the present study to investigate the therapeutic effects of a combination treatment of alfacalcidol (ALF) and risedronate (RIS) on the bone mechanical properties of bone and calcium (Ca) metabolism using an ovariectomized (OVX) rat model of osteoporosis.</p> <p>Methods</p> <p>Female Wistar rats were OVX- or sham-operated at 40 weeks of age. Twelve weeks post-surgery, rats were randomized into seven groups: 1) sham + vehicle, 2) OVX + vehicle, 3) OVX + ALF 0.025 μg/kg/day, 4) OVX + ALF 0.05 μg, 5) OVX + RIS 0.3 mg, 6) OVX + RIS 3.0 mg, 7) OVX + ALF 0.025 μg + RIS 0.3 mg. Each drug was administered orally five times a week for 12 weeks. After treatment, we evaluated the mechanical properties of the lumbar vertebra and femoral midshaft. In the lumbar vertebra, structural and material analyses were performed using micro-computed tomography (micro-CT) and microbeam X-ray diffraction (micro-XRD), respectively. Biochemical markers in serum and urine were also determined.</p> <p>Results</p> <p>(1) With respect to improvement in the mechanical strength of the lumbar spine and the femoral midshaft, the combination treatment of ALF and RIS at their sub-therapeutic doses was more effective than each administered as a monotherapy; (2) In the suppression of bone resorption and the amelioration of microstructural parameters, the effects of ALF and RIS were considered to be independent and additive; (3) The improvement of material properties, such as microstructural parameters and the biological apatite (Bap) c-axis orientation, contributed to the reinforcement of spinal strength; and (4) The combination treatment of ALF and RIS normalized urinary Ca excretion, suggesting that this treatment ameliorated the changes in Ca metabolism.</p> <p>Conclusion</p> <p>These results demonstrate that the combination treatment of ALF and RIS at their sub-therapeutic doses can improve the mechanical properties of the spine as well as the femur and ameliorate changes in Ca metabolism in an animal model of osteoporosis, suggesting that the combination treatment of ALF and RIS has a therapeutic advantage over each monotherapy for the treatment of osteoporosis.</p

The discourse of the two countries about Nung Tri Cao: The "hero" of the ethnic minorities in the Sino-Vietnamese border region

I take up Nung Tri Cao, who established Tai peoples\u27 original kingdom in the Sino-Vietnamese border region in the 11 century, and examine what kind of discourses two countries, China and Vietnam, now use in order to subsume the “Hero of the ethnic minorities” into each history of their own nations in order to integrate their multi-ethnic countries.Nung Tri Cao strongly opposed against the Ly Dynasty of Vietnam, and asked the Tong Dynasty to be subjected many times.But, the Tong Dynasty did not allow him for fear that the relationship with the Ly Dynasty would become worse.Therefore, Nung Tri Cao fought also with the Tong Dynasty, and in the end, was defeated and fled to the Yunnan.When China and Vietnam claimed that they were brother countries of the Socialism, both evaluated Nung Tri Cao as “People” side and two dynasties as “Feudal”.However, through the time when the two countries\u27 relationship turned worse, each evaluation about Nung Tri Cao changed.Now, the discourse of the Guang Xi Province, the home area of Nung Tri Cao in Chinese side, can become official narrative in China.Nung Tri Cao is one of the symbols for many intellectuals of the Guang Xi to assert their ethnic identity to the Chinese central government, and so Nung Tri Cao has been highly evaluated.Their discourse is now distinctive as emphasizing that Nung Tri Cao was against the invasion of the Ly Dynasty and that he cooperated with the Nanhan\u27s scholars who had beaten by Tong Dynasty.This episode was narrated as cooperation between different ethnic groups.On the other hand, in Vietnam, discourses between the central government and the Cao Bang Province, which want to develop tourism as home region of Nung Tri Cao, have not agreed each other.And in accordance with the line of the central government, Nung Tri Cao has not been referred recently as he asked Tong to obey many times.Nung Tri Cao\u27s achievements cannot fulfill the conditions to become a “Hero” of Vietnam.China has now succeeded to include Nung Tri Cao into their national history though he had been talked as a traitor against the Chinese dynasty in pre-modern times, but Vietnam now ignores Nung Tri Cao though some of the people in Cao Bang province still worship Nung Tri Cao.Vietnam failed to include him into their national history

Relationships between insulin resistance, blood glucose levels and gastric motility : an electrogastrography and external ultrasonography study

Background : Detailed information concerning the influence of insulin resistance on gastrointestinal motility are not available. Methods : The relationship between insulin resistance and gastric motility and emptying, and changes in gastric motility with changes in blood glucose level were investigated using electrogastrography (EGG) and external ultrasonography in 20 non-diabetic subjects. The homeostasis model assessment ratio (HOMA-R) was used as an index of insulin resistance. The cut off value for HOMA-R was set at 1.7. Subjects with HOMA-R ≥ 1.7 were the high HOMA-R group, and HOMA-R < 1.7 were the normal HOMA-R group. In the EGG data, a Fast Fourier Transform (FFT) analysis was performed, and the mean peak power was compared among brady-, normal-, and tachy-gastria. Results : In the fasting state, the ratios of brady-gastria in EGG and HOMA-R were significantly positively correlated, and the ratios of normal-gastria and HOMA-R were significantly negatively correlated. When glucose was intravenously administered, the ratio of normal-gastria was significantly decreased and the ratio of brady-gastria was significantly increased in subjects with a high HOMA-R. In a gastric emptying test by external ultrasonography, gastric emptying activity was significantly decreased in subjects with a high HOMA-R. Conclusions : We conclude that insulin resistance induces abnormal gastric motility. Though abnormal gastric motility is related to HOMA-R, the findings herein suggest that incretin, showing insulin resistance, or an adipocyokine might be related to the differences in EGG in both groups. The relation between abnormal gastric motility and other serum parameters (incretin, adipocyokine, etc) would contribute to a better understanding of this process

Defect of Adaptation to Hypoxia in Patients With COPD Due to Reduction of Histone Deacetylase 7

BackgroundHypoxia inducible factor (HIF)-1 plays an important role in cellular adaptation to hypoxia by activating oxygen-regulated genes such as vascular endothelial growth factor (VEGF) and erythropoietin. Sputum VEGF levels are reported to be decreased in COPD, despite hypoxia. Here we show that patients with COPD fail to induce HIF-1α and VEGF under hypoxic condition because of a reduction in histone deacetylase (HDAC) 7.MethodsPeripheral blood mononuclear cells (PBMCs) were obtained from patients with moderate to severe COPD (n = 21), smokers without COPD (n = 12), and nonsmokers (n = 15). PBMCs were exposed to hypoxia (1% oxygen, 5% CO2, and 94% N2) for 24 h, and HIF-1α and HDAC7 protein expression in nuclear extracts were determined by sodium dodecyl sulfate poly acrylamide gel electrophoresis (SDS-PAGE)/Western blotting.ResultsHIF-1α was significantly induced by hypoxia in each group when compared with the normoxic condition (12-fold induction in nonsmokers, 24-fold induction in smokers without COPD, fourfold induction in COPD), but induction of HIF-1α under hypoxia was significantly lower in patients with COPD than in nonsmokers and smokers without COPD (P < .05 and P < .01, respectively). VEGF messenger RNA detected by quantitative real-time polymerase chain reaction was correlated with HIF-1α protein in nuclei (r = 0.79, P < .05), and HDAC7 protein expression was correlated with HIF-1α protein in nuclei (r = 0.46, P < .05). HDAC7 knockdown inhibited hypoxia-induced HIF-1α activity in U937 cells, and HIF-1α nuclear translocation and HIF-1α binding to the VEGF promoter in A549 cells.ConclusionsHDAC7 reduction in COPD causes a defect of HIF-1α induction response to hypoxia with impaired VEGF gene expression. This poor cellular adaptation might play a role in the pathogenesis of COPD

Purification, crystallization and preliminary crystallographic characterization of the α2,6-sialyltransferase from Photobacterium sp. JT-ISH-224

Crystallization of the α2,6-sialyltransferase from Photobacterium

Osteocyte Network; a Negative Regulatory System for Bone Mass Augmented by the Induction of Rankl in Osteoblasts and Sost in Osteocytes at Unloading

Reduced mechanical stress is a major cause of osteoporosis in the elderly, and the osteocyte network, which comprises a communication system through processes and canaliculi throughout bone, is thought to be a mechanosensor and mechanotransduction system; however, the functions of osteocytes are still controversial and remain to be clarified. Unexpectedly, we found that overexpression of BCL2 in osteoblasts eventually caused osteocyte apoptosis. Osteoblast and osteoclast differentiation were unaffected by BCL2 transgene in vitro. However, the cortical bone mass increased due to enhanced osteoblast function and suppressed osteoclastogenesis at 4 months of age, when the frequency of TUNEL-positive lacunae reached 75%. In the unloaded condition, the trabecular bone mass decreased in both wild-type and BCL2 transgenic mice at 6 weeks of age, while it decreased due to impaired osteoblast function and enhanced osteoclastogenesis in wild-type mice but not in BCL2 transgenic mice at 4 months of age. Rankl and Opg were highly expressed in osteocytes, but Rankl expression in osteoblasts but not in osteocytes was increased at unloading in wild-type mice but not in BCL2 transgenic mice at 4 months of age. Sost was locally induced at unloading in wild-type mice but not in BCL2 transgenic mice, and the dissemination of Sost was severely interrupted in BCL2 transgenic mice, showing the severely impaired osteocyte network. These findings indicate that the osteocyte network is required for the upregulation of Rankl in osteoblasts and Sost in osteocytes in the unloaded condition. These findings suggest that the osteocyte network negatively regulate bone mass by inhibiting osteoblast function and activating osteoclastogenesis, and these functions are augmented in the unloaded condition at least partly through the upregulation of Rankl expression in osteoblasts and that of Sost in osteocytes, although it cannot be excluded that low BCL2 transgene expression in osteoblasts contributed to the enhanced osteoblast function

Evaluation of the simulator with automatic irrigation control system designed for countermeasures of internal contamination in dental unit water lines

The prevention of nosocomial infections is an imperative task. The dental chair unit (DCU) is an indispensable device used in dental treatment. However, it is known that the dental unit water line (DUWL) can become contaminated with biofilm, consisting mainly of heterotrophic bacteria (HB). Recently, the International Organization for Standardization specified the methods for testing DUWL contamination management. On these grounds, a simulator reproducing DUWL was prepared to standardize the examination method of the DUWL contamination. Objectives To evaluate the reproducibility of the DUWL simulator, monitor the DUWL contamination states, and test the efficacy of a commercial decontaminant for DUWL. Methods The DUWL simulator was assembled by a DCU manufacturing company. The simulator's DUWL was filled with tap water (TW), and left for approximately one year. Neutral electrolyzed water (NEW) was used as a decontaminant for DUWL. Both TW and NEW were passed through DUWL in a timely manner simulating daily dental treatment. Water was sampled from the air turbine hand piece weekly for 4 weeks and used for HB culture. Contamination status was evaluated by measuring bacterial adenosine triphosphate release and by culturing on Reasoner's 2A medium. Results The DUWL released contaminated water had a bacterial count of over 6 × 104 cfu/mL. After passing NEW through DUWL for 1 week, the count drastically decreased to its basal level and remained steady for 4 weeks. However, TW showed no effect on DUWL decontamination throughout the examination periods. Conclusions The DUWL simulator could be useful to examine the efficacy of the decontaminant for DUWL and development of new methods in DUWL contamination management

The Wnt Signaling Antagonist Kremen1 is Required for Development of Thymic Architecture

Wnt signaling has been reported to regulate thymocyte proliferation and selection at several stages during T cell ontogeny, as well as the expression of FoxN1 in thymic epithelial cells (TECs). Kremen1 (Krm1) is a negative regulator of the canonical Wnt signaling pathway, and functions together with the secreted Wnt inhibitor Dickkopf (Dkk) by competing for the lipoprotein receptor-related protein (LRP)-6 co-receptor for Wnts. Here krm1 knockout mice were used to examine krm1 expression in the thymus and its function in thymocyte and TEC development. krm1 expression was detected in both cortical and medullary TEC subsets, as well as in immature thymocyte subsets, beginning at the CD25+CD44+ (DN2) stage and continuing until the CD4+CD8+(DP) stage. Neonatal mice show elevated expression of krm1 in all TEC subsets. krm1− / − mice exhibit a severe defect in thymic cortical architecture, including large epithelial free regions. Much of the epithelial component remains at an immature Keratin 5+ (K5) Keratin 8+(K8) stage, with a loss of defined cortical and medullary regions. A TOPFlash assay revealed a 2-fold increase in canonical Wnt signaling in TEC lines derived from krm1− / − mice, when compared with krm1+ / + derived TEC lines. Fluorescence activated cell sorting (FACS) analysis of dissociated thymus revealed a reduced frequency of both cortical (BP1+EpCAM+) and medullary (UEA-1+ EpCAMhi) epithelial subsets, within the krm1− / − thymus. Surprisingly, no change in thymus size, total thymocyte number or the frequency of thymocyte subsets was detected in krm1− / − mice. However, our data suggest that a loss of Krm1 leads to a severe defect in thymic architecture. Taken together, this study revealed a new role for Krm1 in proper development of thymic epithelium