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The local environment of aluminum in xLa2O3-(100 -x)Al2O3 (LA) and yY2O3-(100 -y)Al2O3 (YA) glasses is investigated using 27Al MAS NMR and Raman scattering spectroscopy in the glass forming range, i.e., 27 ≤x≤ 50 and 26 ≤y≤ 37.5, respectively. The results suggest that four-fold Al ([4]Al) is predominant in both glasses, with a content of approximately 90% in LA glasses and 60% in YA glasses; the remaining percentages are made up of five- ([5]Al) and six-fold ([6]Al) Al. In LA glasses, the fraction of [4]Al increases slightly with an increase in the La2O3 content, whereas, in YA glasses, the distribution of Al species does not change. Raman scattering spectroscopy reveals that, in LA glasses, the amount of non-bridging oxygen increases with an increase in x; moreover, [5]Al and [6]Al both increase with a decrease in x for x≤ 40. Comparing with alkali earth aluminate glasses, we discuss the relationship between the fundamental structure of the AlO4 network and two parameters (the ratio of the number of oxygen atoms to that of Al and field strength).
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BACKGROUND: Maxillomandibular bone defects arise from maxillofacial injury or tumor/cyst removal. While the standard therapy for bone regeneration is transplantation with autologous bone or artificial bone, these therapies are still unsatisfactory. Autologous bone harvesting is invasive and occasionally absorbed at the implanted site. The artificial bone takes a long time to ossify and it often gets infected. Therefore, we have focused on regenerative therapy consisting of autologous bone marrow-derived mesenchymal cells (BM-MSCs), which decreases the burden on patients. Based on our previous research in patients with maxillomandibular bone defects or alveolar bone atrophy using a mixture of BM-MSCs, platelet-rich plasma (PRP), thrombin, and calcium, we confirmed the efficacy and acceptable safety profile of this treatment. In this investigator-initiated clinical study (the TEOM study), we intended to add ß-tricalcium phosphate (ß-TCP) owing to large defect with patients. The TEOM study aimed to evaluate the efficacy and safety of bone regeneration using mixtures of BM-MSCs in patients with bone defects resulting from maxillofacial injury, and tumor/cyst removal in the maxillomandibular region. METHODS: The TEOM study is an open-label, single-center, randomized controlled study involving a total of 83 segments by the Fédération Dentaire Internationale numbering system in maxillomandibular bone defects that comprise over 1/3 of the maxillomandibular area with a remaining bone height of ≤10 mm. The primary endpoint is rate of procedure sites with successful bone regeneration defined as a computed tomography (CT) value of more than 400 and a bone height of more than 10 mm. Our specific hypothesis is that the number of required regions was calculated assuming that the rate of procedure sites with successful bone regeneration is similar and the non-inferiority margin is 15.0%. DISCUSSION: The TEOM study is the first randomized controlled study of regenerative treatment using BM-MSCs for large maxillomandibular bone defects. We will evaluate the efficacy and safety in this study to provide an exploratory basis for the necessity of BM-MSCs for these patients. TRIAL REGISTRATION: This trial was registered at the University Hospital Medical information Network Clinical Trials Registry (UMIN-CTR Unique ID: UMIN000020398; Registration Date: Jan 15, 2016; URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000016543 ).
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Regeneração Óssea , Doenças Mandibulares/cirurgia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , Osteogênese , Engenharia Tecidual , Medula Óssea , Células da Medula Óssea/citologia , Regeneração Óssea/fisiologia , Humanos , Japão , Doenças Mandibulares/fisiopatologiaRESUMO
The solidification of the SrO-Al2O3 binary system was investigated under containerless conditions using an aerodynamic levitation furnace. Glass formation was observed in compositions with 35-45 mol% SrO and 55-75 mol% SrO. Cooling curves were obtained at a constant cooling rate in the range of 1-1000 °C s(-1). The crystallization temperature was apparently independent of the cooling rate and far below the melting point when the sample was fully crystallized, whereas it decreased when the sample was partially crystallized. The difference between the crystallization temperature and the melting point under containerless conditions is considered a good measure of the glass-forming ability when there is not much difference in the critical cooling rates between the melt compositions. Furthermore, the homogeneous nucleation theory suggests that the apparent time-independent crystallization temperature is attributed to the high glass-forming ability of the SrO-Al2O3 binary system. The results suggest that the experimentally obtained continuous cooling transformation diagrams under containerless conditions provide new insights regarding solidification from an undercooled melt.
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Mesenchymal stem cells (MSCs) have immunomodulatory properties and support hematopoiesis in the bone marrow (BM). To develop a new strategy to not only prevent graft-vs-host disease (GVHD) but also to enhance engraftment, a phase I trial of cord blood transplantation (CBT) combined with intra-BM injection of MSCs (MSC-CBT) was designed. Third-party BM-derived MSCs were injected intra-BM on the day of CBT. The conditioning regimen varied according to patient characteristics. GVHD prophylaxis was tacrolimus and methotrexate. The primary endpoint was toxicity related to intra-BM injection of MSCs. Clinical outcomes were compared with those of six controls who received CBT alone. Five adult patients received MSC-CBT, and no adverse events related to intra-BM injection of MSCs were observed. All patients achieved neutrophil, reticulocyte, and platelet recoveries, with median times to recoveries of 21, 35, and 38 days, respectively, comparable with controls. Grade II-IV acute GVHD developed in three controls but not in MSC-CBT patients. No patients developed chronic GVHD in both groups. At 1 year after transplantation, all MSC-CBT patients survived without relapse. This study shows the safety of MSC-CBT, and the findings also suggest that cotransplantation of MSCs may prevent GVHD with no inhibition of engraftment. This trial was registered at the University Hospital Medical Information Network Clinical Trials Registry as number 000024291.
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Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Mesenquimais , Medula Óssea , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Transplante de Células-Tronco Mesenquimais/métodosRESUMO
To evaluate the latent risk of acidosis in commercially available total parenteral nutrition (TPN) products, three types of commercially available TPN products were compared in postoperative patients. Sixty-four hospitalized patients with gastro-intestinal disease who undertook curative gastro intestinal resection were studied prospectively and administered with TPN solutions. Three types of commercially available TPN products were assigned randomly to eligible patients. Serial studies of blood acid-base status, serum electrolytes, and urinary acid-base status were conducted in the three groups administered with different TPN solutions. Patients received appropriate electrolytic solutions on the operation day and TPN solution from 2 to 7 days after operation. There were no differences among any of the serum electrolytes in the three groups. In one group, urinary pH decreased slightly and urinary net acid excretion (NAE) increased significantly after administration. This TPN product contains about 40 mEq/L of non-metabolizable acid to avoid the Maillard reaction that produces a complex of glucose and amino acids. Urinary NAE did not change in the other two groups. These TPN products do not use non-metabolizable acid to adjust pH. The present results suggest that the non-metabolizable acid may be a risk factor of metabolic acidosis.
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INTRODUCTION: Delayed hematological recovery, graft failure, and acute graft-versus-host disease (GVHD) still remain major problems in cord blood transplantation (CBT). Mesenchymal stem cells (MSCs) are known to support bone marrow stroma and promote hematopoiesis. Additionally, MSCs possess immunomodulatory properties and are used clinically for the treatment of acute GVHD. Therefore, the use of MSCs to enhance engraftment and prevent GVHD after allogeneic hematopoietic cell transplantation has been explored. Recent clinical trials have shown the feasibility and safety of intravenous cotransplantation of MSCs with cord blood cells in pediatric patients, but not in adult patients, who are at greater risk of graft failure. As for the route of administration of MSCs, direct intrabone marrow injection of MSCs is thought to enhance the engraftment of cord blood cells more than intravenous injection. Based on these background findings, this clinical trial was designed to develop a new strategy to enhance engraftment and prevent GVHD after CBT. METHODS AND ANALYSIS: This is a single-center, phase I, clinical study to evaluate the safety of CBT combined with intrabone marrow injection of ex vivo expanded MSCs from bone marrow of a third-party donor. Adult patients with hematological disorders are eligible for this study. The target sample size is 5, and the registration period is 3 years. The target dose of MSCs infused is 0.5â×â10âcells/kg of patient body weight. On the day of CBT, MSCs are injected into the intrabone marrow of the patient 4âhours before the infusion of a single cord blood unit. The conditioning regimen varies according to patient age and disease. GVHD prophylaxis consists of a combination of tacrolimus and methotrexate. The primary endpoint of this study is infusional toxicity of MSCs within 14 days after transplantation.
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Medula Óssea , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Condicionamento Pré-Transplante/métodos , Humanos , Transplante de Células-Tronco Mesenquimais/métodosRESUMO
Glasses with high elastic moduli have been in demand for many years because the thickness of such glasses can be reduced while maintaining its strength. Moreover, thinner and lighter glasses are desired for the fabrication of windows in buildings and cars, cover glasses for smart-phones and substrates in Thin-Film Transistor (TFT) displays. In this work, we report a 54Al2O3-46Ta2O5 glass fabricated by aerodynamic levitation which possesses one of the highest elastic moduli and hardness for oxide glasses also displaying excellent optical properties. The glass was colorless and transparent in the visible region, and its refractive index nd was as high as 1.94. The measured Young's modulus and Vickers hardness were 158.3 GPa and 9.1 GPa, respectively, which are comparable to the previously reported highest values for oxide glasses. Analysis made using (27)Al Magic Angle Spinning Nuclear Magnetic Resonance (MAS NMR) spectroscopy revealed the presence of a significantly large fraction of high-coordinated Al in addition to four-coordinated Al in the glass. The high elastic modulus and hardness are attributed to both the large cationic field strength of Ta(5+) ions and the large dissociation energies per unit volume of Al2O3 and Ta2O5.