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

Laparoscopic resection of a gastrointestinal stromal tumor larger than 5 cm: Report of a Case

A 46-year-old woman was admitted to our hospital and was diagnosed with a gastric submucosal tumor at the medical examination. Upper endoscopic examination revealed a submucosal tumor in the lower body of the stomach. Abdominal computed tomography (CT) revealed a large tumor of dimensions 51 × 32 mm in the lower body of the stomach with a mixed appearance: a solid part exhibiting a contrast effect and a cystic part exhibiting no contrast. Endoscopic ultrasonic fine needle aspiration biopsy (EUS-FNAB) was performed, and a gastrointestinal stromal tumor (GIST) was diagnosed by immunohistopathological examination. Laparoscopic surgery with five ports was performed for resection. After securing the safety margin the tumor was resected circumferentially using an ultrasonically activated device (USAD). Resection entailed a significant portion of the gastric wall. During surgery, a support yarn hooked in the minor axis direction, and the defect was closed using an automatic suturing device three times. According to the third edition of the GIST clinical practice guidelines, indications for laparoscopic resection of GISTs over 5cm have been relaxed. It was considered that careful laparoscopic resection would be possible even though this was a large GIST exceeding 5 cm

Laparoscopic resection of a gastrointestinal stromal tumor larger than 5 cm: Report of a Case

A 46-year-old woman was admitted to our hospital and was diagnosed with a gastric submucosal tumor at the medical examination. Upper endoscopic examination revealed a submucosal tumor in the lower body of the stomach. Abdominal computed tomography (CT) revealed a large tumor of dimensions 51 × 32 mm in the lower body of the stomach with a mixed appearance: a solid part exhibiting a contrast effect and a cystic part exhibiting no contrast. Endoscopic ultrasonic fine needle aspiration biopsy (EUS-FNAB) was performed, and a gastrointestinal stromal tumor (GIST) was diagnosed by immunohistopathological examination. Laparoscopic surgery with five ports was performed for resection. After securing the safety margin the tumor was resected circumferentially using an ultrasonically activated device (USAD). Resection entailed a significant portion of the gastric wall. During surgery, a support yarn hooked in the minor axis direction, and the defect was closed using an automatic suturing device three times. According to the third edition of the GIST clinical practice guidelines, indications for laparoscopic resection of GISTs over 5cm have been relaxed. It was considered that careful laparoscopic resection would be possible even though this was a large GIST exceeding 5 cm

Effects of eldecalcitol on bone and skeletal muscles in glucocorticoid treated rats

Glucocorticoid causes secondary osteoporosis and myopathy, characterized by type II muscle fiber atrophy. We examined whether a new vitamin D3 analog, eldecalcitol, could inhibit glucocorticoid-induced osteopenia or myopathy in rats and determined the effects of prednisolone (PSL) and/or eldecalcitol on muscle-related gene expression. Six-month-old female Wistar rats were randomized into four groups: PSL group (10 mg/kg PSL); E group (0.05 µg/kg eldecalcitol); PSL + E group; and control group. PSL, eldecalcitol, and vehicles were administered daily for 2 or 4 weeks. Right calf muscle strength, muscle fatigue, cross-sectional areas (CSAs) of left tibialis anterior muscle fibers, and bone mineral density (BMD) were measured following administration. Pax7, MyoD, and myogenin mRNA levels in gastrocnemius muscles were also determined. The PSL + E group muscle strength was significantly higher than that of the PSL group (p < 0.05) after 4 but not 2 weeks. There was no significant difference in muscle fatigue between the groups at 2 or 4 weeks. The CSAs of type II muscle fibers were significantly larger in the E group and PSL + E group than the PSL group at 4 weeks (p = 0.0093, p = 0.0443, respectively). Eldecalcitol treatment for 4 weeks maintained the same BMD as the PSL + E group. After 2 but not 4 weeks, eldecalcitol treatment significantly increased Pax7 and myogenin mRNA expression in gastrocnemius muscle, while PSL also stimulated myogenin expression. Eldecalcitol appears to increase muscle volume and protect against femur BMD loss in PSL-administered rats. It may also stimulate myoblast differentiation into early myotubes

Estimation of Carbon Storage and Its Change in the Tokyo University Forest in Chiba : Comparison between 1995 and 1909

東京大学農学部附属千葉演習林を対象として森林簿およびGISによって1995年と1909年の炭素蓄積量を推定し，時期の違いおよび手法の違いによる炭素蓄積量の比較を行った。結果は表に加え，GISによる炭素蓄積地図として示した。その解析には林木材積に樹種固有の炭素密度を乗じて炭素蓄積量（ton）を求める「積み上げ法」を用い，天然生林樹種構成は現地調査と文献から推定した。千葉演習林全体の炭素蓄積量は1909年から1995までの間に約3.8～3.1倍増加した。また，1995年の千葉演習林における人天別炭素蓄積量を比べると，単位面積当たり平均炭素蓄積量で約1.5倍人工林の方が大きかった。千葉演習林における単位面積当たり炭素蓄積量と森林クラスとの相関を見ると，炭素蓄積量100～200（ton/ha）は人工林の70～90年生，200～300（ton/ha）は森林クラスにかかわらず100年生以上の林分が多かった。Forests have recently been highlighted for their long-term carbon absorbing function with the expectation that they can moderate global warming. This study aims to estimate the amount of carbon storage at two different times in the University Forest in Chiba where management plans have been kept since 1905. The amount of carbon in the years 1909 and 1995 were estimated, mainly with calculations based on the inventory database. Though carbon density differs by species, there was no precise species composition information in inventory database for either year. So temporal field measurement plots were established to estimate the species composition of the present natural forests. In addition to the estimated results, GIS maps were made from forest type maps for comparing the two times. As a result firstly, the total amount of carbon storage in the University Forest in Chiba in 1995 is estimated to be about 3.1 to 3.8 times larger than that in 1909. Secondly, plantation forest is superior to natural forest in terms of carbon absorption. Plantation forest absorbs about 1.5 times more carbon per hectare. Therefore, this study revealed that the afforestation activities since the establishment of the University Forest in Chiba is effective from the viewpoint of carbon storage. In the near future, it will also be necessary to develop a method to estimate carbon in the soil, which will lead to an estimate of the total amount of carbon storage in the forest

A case of infantile Barth syndrome with severe heart failure: Importance of splicing variants in the TAZ gene.

Barth syndrome (BTHS) is an X-linked disorder characterized by cardiomyopathy, skeletal myopathy, and 3-methylglutaconic aciduria. The causative pathogenic variants for BTHS are in TAZ, which encodes a putative acyltransferase named tafazzin and is involved in the remodeling of cardiolipin in the inner mitochondrial membranes. Pathogenic variants in TAZ result in mitochondrial structural and functional abnormalities. We report a case of infantile BTHS with severe heart failure, left ventricular noncompaction, and lactic acidosis, having a missense c.640C>T (p.His214Tyr) variant in TAZ, which is considered a pathogenic variant based on the previously reported amino acid substitution at the same site (c.641A>G, p.His214Arg). However, in this previously reported case, heart function was compensated and not entirely similar to the present case. Silico prediction analysis suggested that c.640C>T could alter the TAZ messenger RNA (mRNA) splicing process. TAZ mRNAs in isolated peripheral mononuclear cells from the patient and in vitro splicing analysis using minigenes of TAZ found an 8 bp deletion at the 3' end of exon 8, which resulted in the formation of a termination codon in the coding region of exon 9 (H214Nfs*3). These findings suggest that splicing abnormalities should always be considered in BTHS

Expression of MHC Class I on breast cancer cells correlates inversely with HER2 expression

HER2 is a promising target for immunotherapeutic interventions with T cell-based approaches since it is amplified and overexpressed in 20–30% of breast cancers. However, several previous studies including ours showed that HER2-overexpressing tumors may escape cytotoxic T lymphocyte-mediated lysis by downregulating MHC Class I and components of the antigen-processing machinery. The aims of the present study were to analyze the relationship between HER2 and MHC Class I expression and to elucidate the mechanisms underlying MHC Class I downregulation in breast cancer. We explored expression of HER2, MHC Class I, PTEN, Ki67, estrogen and progesterone expression in 70 breast cancer patients by immunohistochemistry (IHC) and analyzed their correlation. We also explored the components of the signal transduction pathway that are involved in the regulation of MHC Class I expression using small-interfering RNAs targeting HER2 as well as an inhibitor of HER2 signaling. HER2 expression in breast cancers correlated inversely with MHC Class I expression analyzed by IHC. HER2 depletion by small-interfering RNAs resulted in MHC Class I upregulation. Moreover, MHC Class I expression on breast cancer cell lines was upregulated by PD98059, an inhibitor of mitogen-associated protein kinases, in a dose-dependent manner. Thus, agents that target the MAPK signaling pathway may increase MHC Class I expression in breast cancer cells