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B(C6F5)3‐catalyzed tandem double hydrofunctionalization reactions initiated by intramolecular hydroamination of unactivated alkynes are described herein. In the hydroamination/hydroallylation reaction, in situ preparation of anhydrous B(C6F5)3 from B(C6F5)3 ⋅ nH2O and the use of 2,6‐di‐tert‐butylphenol as a proton source were effective. In the hydroamination/hydrocyanation reaction, a combination of B(C6F5)3 ⋅ nH2O and H2O as the proton source provided good results., ファイル公開：2020/07/01

To understand the genetics of steroid-sensitive nephrotic syndrome (SSNS), we conducted a genome-wide association study in 987 childhood SSNS patients and 3,206 healthy controls with Japanese ancestry. Beyond known associations in the HLA-DR/DQ region, common variants in NPHS1-KIRREL2 (rs56117924, P=4.94E-20, odds ratio (OR) =1.90) and TNFSF15 (rs6478109, P=2.54E-8, OR=0.72) regions achieved genome-wide significance and were replicated in Korean, South Asian and African populations. Trans-ethnic meta-analyses including Japanese, Korean, South Asian, African, European, Hispanic and Maghrebian populations confirmed the significant associations of variants in NPHS1-KIRREL2 (P(meta)=6.71E-28, OR=1.88) and TNFSF15 (P(meta)=5.40E-11, OR=1.33) loci. Analysis of the NPHS1 risk alleles with glomerular NPHS1 mRNA expression from the same person revealed allele specific expression with significantly lower expression of the transcript derived from the risk haplotype (Wilcox test p=9.3E-4). Because rare pathogenic variants in NPHS1 cause congenital nephrotic syndrome of the Finnish type (CNSF), the present study provides further evidence that variation along the allele frequency spectrum in the same gene can cause or contribute to both a rare monogenic disease (CNSF) and a more complex, polygenic disease (SSNS).

PURPOSE Dysphagia following heart failure (HF) has gained little attention. This study aimed to evaluate the incidence of dysphagia and its associations with the clinical outcomes in HF patients. METHODS This prospective cohort study included 203 consecutive hospitalized HF patients (mean age 79.5 years, 103 women) without dysphagia before admission. Dysphagia or difficulty swallowing was assessed by the Food Intake Level Scale. The primary outcome was activity of daily living, as assessed by the Barthel Index (BI) at discharge. Secondary outcomes included all-cause mortality and rehospitalization rates at 1 year after discharge. Multivariate analyses and Kaplan-Meier estimates were used to determine whether dysphagia was associated with these outcomes. RESULTS Of the 203 patients examined, 48 (23.4%) were diagnosed with dysphagia during admission. Patients who developed dysphagia were significantly older, exhibited lower muscle mass and strength, walked shorter distances, and had lower nutrition intake levels and BI scores (P < 0.05 for all values) compared with those without dysphagia. In the multivariate analyses, the presence of dysphagia at discharge was significantly associated with a lower BI (β= -0.275, P < 0.001). Furthermore, patients with dysphagia showed a significantly higher 1-year mortality than those without (20.8% vs 1.2%, P = 0.008). CONCLUSIONS Dysphagia commonly occurs during hospital admission and is associated with functional recovery and 1-year mortality in HF patients.

AIM Patients who experience heart failure are prone to malnutrition. The aim of this study was to determine the association between risk of malnutrition and physical function in patients undergoing cardiac rehabilitation following heart failure. METHODS A cross-sectional study was performed in consecutive patients hospitalised for cardiac rehabilitation following heart failure. Risk of malnutrition was evaluated using the Mini Nutritional Assessment-Short Form (MNA-SF). Physical function was evaluated using the Barthel index (BI). Univariate and multivariate analyses were used to determine whether nutritional status was associated with BI in these patients. RESULTS The present study included 105 patients (mean age of 77.3 years, 56 men and 49 women) for analysis. The median (interquartile range) scores of the MNA-SF and BI were 11 (9-13) and 75 (45-90), respectively. Patients with high risk of malnutrition (MNA-SF score

Tandem hydroalkoxylation/hydroallylation and hydroalkoxylation/hydrocyanation reactions of alkyl-substituted unactivated alkynes by catalytic systems based on B(C6F5)3·nH2O and silyl nucleophiles were developed. The characteristic high alkynophilicity of B(C6F5)3 enabled the selective activation of the unactivated alkynes in the presence of the reactive alkene of allylsilane. Moreover, the alkynes were electrophilically activated in the presence of cyanide in this catalytic system. Mechanistic studies suggest that the alkynes are activated by the different catalytic species in the two reactions.

Objectives This study evaluated the relationship between systemic inflammation and clinical outcomes in people hospitalized with acute heart failure (AHF). Methods We prospectively enrolled people newly hospitalized with AHF after excluding those with concomitant infectious or inflammatory diseases. Systemic inflammation was evaluated using the modified Glasgow Prognostic Score (mGPS) at hospitalization, and participants were classified into low-grade and high-grade inflammation groups (mGPS 0–1 and 2, respectively). The primary outcome measure was functional recovery, evaluated using the Barthel Index gain. Secondary outcome measures were dysphagia at discharge and all-cause 1-y mortality after discharge. Multivariable analyses and Kaplan-Meier estimates were used to determine the association between systemic inflammation and study outcomes. Results A total of 184 participants (mean age, 79.1 y; 48.4% female, 51.6% male) were included; 148 (80.4%) and 36 (19.6%), respectively, had low-grade and high-grade inflammation. Participants with high-grade inflammation were significantly older, had lower body mass index and muscle strength, and had lower nutrient intake, swallowing status, and Barthel Index than those with low-grade inflammation. In multivariable analyses, mGPS was significantly associated with Barthel Index gain (β = −0.229, P = 0.004) and Food Intake Level Scale (odds ratio = 5.067, P = 0.034) at discharge; mGPS was associated with 1-y mortality after discharge (P = 0.003). Conclusions Baseline systemic inflammation was negatively associated with improvements in physical function and dysphagia and with 1-y survival in people with AHF. These findings highlight the importance of focusing on the assessment of systemic inflammation to accurately predict the functional prognosis of people with AHF.

A transition-metal-free silane–iodine catalytic system comprising I2 and Et3SiH promotes intramolecular hydroalkoxylation/reduction and hydroamination/reduction of unactivated alkynes. This system allows the reaction to proceed at room temperature affording 2,4- and 2,5-disubstituted pyrrolidines as well as a 2,3-disubstituted tetrahydrofuran with high diastereoselectivity.

The Brønsted acid-catalyzed intramolecular hydroalkoxylation and hydroamination of unactivated alkynes are described. We found that unactivated alkynes are electrophilically activated by a catalytic amount of bis(trifluoromethanesulfonyl)imide to undergo intramolecular hydroalkoxylation and hydroamination. In the presence of silane, the formed reactive exo-cyclic enol ether and exo-cyclic enamine intermediates are effectively reduced to the corresponding saturated cyclic ethers and N-protected cyclic amines. The 2,4-cis and 2,5-cis pyrrolidine derivatives are produced with high diastereoselectivity. Taking advantage of this selectivity, the 2,5-cis-disubstituted prolinol was also synthesized from glutamic acid in the optically active form.

Dysphagia is an important clinical problem in older adults with heart failure. Moreover, evidence is scarce regarding the prevalence and impact of dysphagia on physical function in these patients. This study examined the association of dysphagia and physical function in patients undergoing cardiac rehabilitation following heart failure. This prospective cohort study included consecutive 149 (mean age 78.6 years, 72 women) inpatients in an acute-care hospital. Outcomes included the Food Intake Level Scale (FILS) and Barthel Index (BI) as indicators of dysphagia status and physical function, respectively. Multivariate analyses were used to determine whether FILS scores on admission and at the point of heart failure stabilization were associated with BI at discharge. Of the 149 patients, 14 (9.4%) had dysphagia at the time of stabilization of heart failure. Patients with dysphagia (FILS score

It was observed that a PhSiH2I-mediated protocol using PhSiH3 and cat. I2 caused the deiodination of 2-(iodomethyl)-2-phenyltetrahydrofuran. Stemming from the investigation of the mechanism, we found that the PhSiH3-I2 system selectively promotes diverse cascade transformations from cyclic ethers to acyclic alkyl iodides, and the PhSiH3-N-iodosuccinimide (NIS) system also promotes cascade transformations from cyclic ethers to acyclic alcohols.

BACKGROUND Stem cell transplantation (SCT) outcomes have improved over the last three decades, with many patients being rescued with this treatment. However, improved outcomes have led to issues with long-term sequelae. One of these sequelae in children is renal dysfunction, an index of which is estimated using glomerular filtration rate (eGFR). PROCEDURE We retrospectively analyzed eGFR in 83 pediatric patients who received SCT. Data from all patients extended up to 12 months or more post SCT. The median follow-up time was 127.7 months (range 12.0-268.8 months). RESULTS Eighteen patients (21.7%) had low eGFR (

Patients who experience heart failure are prone to malnutrition. The aim of this study was to determine the association between risk of malnutrition and physical function in patients undergoing cardiac rehabilitation following heart failure.A cross-sectional study was performed in consecutive patients hospitalised for cardiac rehabilitation following heart failure. Risk of malnutrition was evaluated using the Mini Nutritional Assessment-Short Form (MNA-SF). Physical function was evaluated using the Barthel index (BI). Univariate and multivariate analyses were used to determine whether nutritional status was associated with BI in these patients.The present study included 105 patients (mean age of 77.3 years, 56 men and 49 women) for analysis. The median (interquartile range) scores of the MNA-SF and BI were 11 (9-13) and 75 (45-90), respectively. Patients with high risk of malnutrition (MNA-SF score 7) were significantly older, had a lower body mass index, exhibited lower muscle mass and strength, could walk shorter distances, and had lower BI scores (all P 0.05). On multivariate analysis, the MNA-SF score was independently associated with BI (β = 0.409, P 0.001) after adjusting for age, sex, muscle mass and strength, brain natriuretic peptide levels, ejection fraction of the left ventricle, and reason for admission.Risk of malnutrition is associated with physical function in patients undergoing cardiac rehabilitation following heart failure. Early detection of malnutrition and commencement of nutritional support may improve functional recovery in these patients.

Background Recent evidence suggests that atrial fibrillation (AF) adversely affects endothelial function. The goal of this study was to assess endothelial function in patients with AF before and after restoration of sinus rhythm by catheter ablation (ABL). Methods Reactive hyperemia peripheral arterial tonometry (RH-PAT) measurements reflecting endothelial function were conducted with Endo-PAT2000 (Itamar Medical, Caesarea, Israel) in 27 patients with persistent AF before ABL and in 21 control subjects with sinus rhythm (SR). According to cardiac rhythm on the morning after ABL, patients were divided into two groups: day 1-restored SR group (n=19) and day 1-recurred AF group (n=8). Based on the cardiac rhythm at 6months after ABL, the restored SR group was further subdivided into the month 6-maintained SR group (n=11) and the month 6-recurred AF group (n=6). Results Log e RH-PAT index (RHI) was significantly lower in the persistent AF group than in the control (SR) group (0.52±0.20; 0.69±0.24, p e RHI e RHI was significantly higher after ABL than before ABL (0.53±0.20; 0.73±0.25; p e RHI of the month 6-maintained SR group was comparable to that of the day 1-restored SR group. Conclusions These results suggest that AF is associated with impairment of endothelial dysfunction and that this impairment is reversed by restoration of sinus rhythm.

Objective The aim of this study was to investigate how atopic dermatitis (AD) contributes to root resorption during orthodontic tooth movement. Materials and Methods Atopic dermatitis model mice and wild-type mice were subjected to an excessive orthodontic force (OF) to induce movement of the upper first molars. The expression levels of the tartrate-resistant acid phosphatase (TRAP), IL-17, IL-6, and RANKL proteins were determined in the periodontal ligament (PDL) by an immunohistochemical analysis. Furthermore, the effects of the compression force on co-cultures of CD4+ cells from AD patients or healthy individuals and human PDL cells were investigated with regard to the levels of secretion and mRNA expression of IL-17, IL-6, RANKL, and osteoprotegerin. Results The immunoreactivities for TRAP, IL-17, IL-6, and RANKL in the AD group were found to be significantly increased. The double immunofluorescence analysis for IL-17/CD4 detected immunoreaction. The secretion of IL-17, IL-6, and RANKL, and the mRNA levels of IL-6 and RANKL in the AD patients were increased compared with those in healthy individuals. Conclusion Th17 cells may therefore be associated with the deterioration of root resorption of AD mice, and may explain why AD patients are more susceptible to root resorption than healthy individuals when an excessive OF is applied.

Extrarenal nephroblastoma (ERNB) is a rare disease. We report a case of ERNB in a 4-year-old boy complaining of abdominal pain and vomiting. Imaging showed a retroperitoneal mass and left hydronephrosis. The mass was completely removed by surgery. The pathologic diagnosis was ERNB with favorable histology. Postoperative chemotherapy was administered for 24 weeks with actinomycin D, vincristine, and doxorubicin. No signs of recurrence were found for the next 3 years. We consider 53 reports of ERNB and our own. Median age at diagnosis was 42 months. The most common site is the retroperitoneal space (44.4%), followed by the uterus (14.8%).

The aim of this study was to investigate the amount of external apical root resorption (EARR) and the release of interleukin (IL)-6 in the gingival crevicular fluid (GCF) in subjects treated with a low-force low-friction system. Sixty patients were assigned to two groups of thirty patients for each: one group received treatment with self-ligating brackets and the other with conventional ligated edgewise brackets. All patients were treated with extraction of the maxillary first premolars. The EARR of the maxillary central incisors was evaluated on the periapical radiographs and cephalograms, taken before and after orthodontic treatment. The GCF was also collected non-invasively from the mesial and distal sides of central incisors by using filter paper strips before and after orthodontic treatment. Enzyme-linked immunosorbent assay (ELISA) kits were used to determine the IL-6 levels in the GCF samples. A significant difference was found in the amount of EARR between the patients with self-ligating brackets and conventional brackets. The mean amount of EARR was significantly lower for self-ligating brackets than conventional brackets (p < 0.05). The GCF levels of IL-6 for the patients with self-ligating brackets appliance were significantly lower than for those with the conventional brackets (p < 0.05). These results show that the mean amount of EARR and the GCF levels of IL-6 were significantly lower in the patients treated using low-force low-friction appliances than conventional brackets. Therefore, self-ligating brackets may be a useful system for reducing inflammation and EARR.

The novel catalytic system is used successfully for the preparation of a broad spectrum of substituted furans and some pyran structures.

Background: A previous report by our team showed that Waon therapy, using a far infrared-ray dry sauna at 60°C, improves cardiac and vascular function in patients with chronic heart failure (CHF). The purpose of the present study was to clarify the effect of Waon therapy on oxidative stress in CHF patients and investigate its mechanism by animal experiments. Methods and Results: Forty patients with CHF were divided into control (n=20) and Waon therapy (n=20) groups. All patients received standard optimal medications for CHF. Waon therapy group was treated with Waon therapy daily for 4 weeks. After 4 weeks of Waon therapy, concentrations of hydroperoxide and brain natriuretic peptide (BNP) decreased significantly (hydroperoxide, 422±116 to 327±88U.CARR, P

Oral Diseases (2011) 17, 489–498 Objective: The aim of this study was to investigate how interleukin (IL)-8 (cytokine-induced neutrophil chemoattractant; CINC-1) and monocyte chemotactic protein (MCP)-1/CCL2 contribute to root resorption during orthodontic tooth movement. Materials and methods: Forty 6-week-old male Wistar rats were subjected to orthodontic force of 10 or 50 g to induce a mesially tipping movement of the upper first molars for 7 days. We determined the expressions of CINC-1, CXCR2, and MCP-1 proteins in root resorption area using immunohistochemistry. Furthermore, we investigated the effects of compression forces (CF) on IL-8 and MCP-1 production by human periodontal ligament (hPDL) cells. We observed an effect of chemokine treatment on rat odonto/osteoclasts in dentin slices that recapitulated root resorption. Results: The immunoreactivity for CINC-1/CXCR2 and MCP-1 was detected in odontoclasts and PDL fibroblasts by the orthodontic force of 50 g on day 7. CF increased the secretion and the expression of mRNA of IL-8 and MCP-1 from PDL cells in a magnitude-dependent manner. Moreover, CINC-1 and MCP-1 stimulated osteoclastogenesis from rat osteoclast precursor cells. Conclusion: IL-8 (CINC-1) and MCP-1 may therefore facilitate the process of root resorption because of excessive orthodontic force.

SummaryBackgroundWe previously reported that Waon therapy upregulates endothelial nitric oxide synthase protein, and augments ischemia-induced angiogenesis in mice with hindlimb ischemia, and it improves limb ischemia in patients with peripheral arterial disease (PAD). The aim of this study was to investigate the underlying mechanism of Waon therapy for the treatment of patients with PAD, and to determine whether Waon therapy can mobilize blood-derived progenitor cells.Methods21 consecutive PAD patients received standard medications, and were randomly divided into control (n=10) and Waon therapy groups (n=11). The Waon therapy group received Waon therapy daily for 6 weeks. The control group continued conventional therapy for 6 weeks. Leg pain was scored using a visual analogue scale. The ankle-brachial pressure index (ABPI) and the 6-min walking distance were measured at baseline and 6 weeks after therapy. Frequency of circulating CD34+ progenitor cell numbers was measured by quantitative real-time polymerase chain reaction, and the serum nitrate and nitrite levels were also measured at baseline and 6 weeks after therapy.ResultsThe leg pain score, ABPI and the 6-min walking distance improved significantly after 6 weeks in the Waon therapy group, but not in the control group. Frequency of circulating CD34+ cells increased after 6 weeks of Waon therapy [2.0±1.2 (×10−4) at baseline to 3.9±1.9 (×10−4), p=0.015], while it remained unchanged in the control group [1.8±1.8 (×10−4) at baseline to 1.2±0.9 (×10−4)]. Serum nitrate and nitrite levels increased significantly after Waon therapy (29.6±17.6 to 36.0±17.7μmol/ml, p

The differentiation and functions of osteoclasts are regulated by receptor activator of nuclear factor-κB (RANK)/receptor activator of nuclear factor-κB ligand (RANKL) system that stimulates osteoclasts formation. Macrophage colony-stimulating factor (M-CSF) is also essential for osteoclastogenesis. A recent immunocytochemical study reported that RANKL/RANK and M-CSF/ c-fms were localized in the periodontal ligament of rat molars during experimental orthodontic tooth movement. The present study focused on the expressions of RANKL/RANK and M-CSF/ c-fms in root resorption area during experimental tooth movement in rats. Forty 6-week-old male Wistar rats were subjected to an orthodontic force of 10 or 50 g with a closed coil spring (wire size: 0.005 inch, diameter: 1/12 inch) ligated to the maxillary first molar cleat by a 0.008 inch stainless steel ligature wire to induce a mesial tipping movement of the upper first molars. Experimental tooth movement was undertaken for 10 days. Each sample was sliced into 6 μm continuous sections in a horizontal direction and prepared for haematoxylin and eosin (H and E) and immunohistochemistry staining for tartrate-resistant acid phosphatase (TRAP), RANK, RANKL M-CSF, and c-fms in root resorption area. Statistical analysis was carried out using a Mann–Whitney U -test with a significance level of P < 0.01. On days 7 and 10, immunoreactivity for RANKL/RANK and M-CSF/ c-fms was detected in odontoclasts with an orthodontic force of 50 g, but not 10 g. Therefore, RANKL/RANK and M-CSF/ c-fms systems may be involved in the process of root resorption by heavy orthodontic force.

Heat shock proteins (HSPs) play an important role in maintaining protein homeostasis within the cell, and they are also related to inflammation. However, it is not clear how HSPs regulate inflammatory cytokines in periodontal ligament (PDL) cells during mechanical stress. The present study focuses on the expression of HSP70 in the PDL during experimental tooth movement in rats. A total of 35 6-week-old male Wistar rats were subjected to orthodontic force of 10 g to induce mesial tipping movement of the upper first molars. Experimental tooth movement was accomplished for 14 days. We determined the expression of HSP70 proteins in the PDL during orthodontic tooth movement by immunohistochemistry. HSP70 immunoreactivity was detected in PDL fibroblasts on the compressive side by an orthodontic force of 10 g. On day 1 after tooth movement, the immunoreactivity of HSP70 was weak. On days 2, 3 and 4, we identified a greater positive reaction for HSP70 in the nucleus of fibroblasts than that recognized on the first day. The HSP70-positive reaction further increased on days 7 and 14. From our quantitative evaluation, the rate of HSP70-positive PDL fibroblasts significantly increased compared with control fibroblasts, and this occurred in a time-dependent manner. Therefore, HSP70 may function as a homeostatic factor to compensate for PDL-cell changes that occur during orthodontic force.

Aim: The aim of this study was to investigate the role of uric acid (UA) in coronary endothelial function via its effects on renal function, other coronary risk factors and asymmetric dimethylarginine (ADMA) in men and women.Methods: The study population consisted of 194 consecutive patients (119 men and 75 women) without coronary artery disease. The relationships between UA and coronary endothelial function, estimated glomerular filtration rate (eGFR), ADMA or other biochemical or anthropometric parameters were investigated.Results: Monovariate analysis of female participants demonstrated that % change in coronary blood flow (CBF) induced by acetylcholine (ACh) was inversely correlated with UA, ADMA and age (r=-0.32, p

SummaryBackgroundWe developed a Waon therapy (soothing warm therapy) and have previously reported that repeated Waon therapy improves hemodynamics, peripheral vascular function, arrhythmias, and clinical symptoms in patients with chronic heart failure (CHF). The aim of this study was to investigate the effect of Waon therapy on the prognosis of CHF patients.Patients and methodsWe studied 129 patients with CHF in NYHA functional class III or IV who were admitted to our hospital between January 1999 and March 2001. In the Waon therapy group, 64 patients were treated with a far infrared-ray dry sauna at 60°C for 15min and then kept on bed rest with a blanket for 30min. The patients were treated daily for 5 days during admission, and then at least twice a week after discharge. In the control group, 65 patients, matched for age, gender, and NYHA functional class, were treated with traditional CHF therapy. The follow-up time was scheduled for 5 years.ResultsRecent, complete follow-up data on each patient were obtained. The overall survival rate was 84.5% (Kaplan–Meier estimate). Twelve patients died in the control group and 8 patients died in the Waon therapy group at 60 months of follow-up. Cardiac events due to heart failure or cardiac death occurred in 68.7% of the control group but only 31.3% of the Waon therapy group (P

Many studies have suggested that inflammation may participate in the pathogenesis of non-valvular atrial fibrillation (AF). However, it has been unknown by exposure to what the inflammation is caused. Recently, we reported that Toll-like receptor 2 (TLR2) level on monocytes was significantly up-regulated in viral and bacterial infections, but not in non-infectious inflammatory states. Our purpose was to test the hypothesis that expression of TLR2 levels may be up-regulated in patients with non-valvular AF. A total of 48 consecutive patients with non-valvular AF who were hospitalized for catheter ablation were enrolled in this study. TLR2 levels were assayed by using flow-cytometric analysis and compared with volunteers in sinus rhythm (control group, n = 24). Additionally, C-reactive protein (CRP) and interleukin-6 (IL-6) levels were assayed, and the left atrial volume indexes (LAVI) in the non-valvular AF group were measured. The results demonstrated that TLR2 levels in the non-valvular AF group were significantly higher than in the control group (median, 4682 vs. 3866 sites/cell; P < 0.01). Moreover, non-valvular AF patients had significantly higher IL-6 levels than controls. However, there was no significant difference in CRP levels between the two groups. It was observed in 44 AF patients, in whom pulmonary vein isolation was confirmed to be successful, that the LAVI significantly diminished 1 month after ablation (median, 33.6 vs. 29.5 ml/m²; P < 0.001), but not the TLR2 and IL-6 levels. Our results implied that an infectious inflammation may participate in the pathogenesis of non-valvular AF.

The differentiation and functions of osteoclasts are regulated by the receptor activator of nuclear factor kappa beta (RANK) and its ligand (RANKL). The present study was designed to identify the expression of RANK/RANKL in the event of root resorption provoked by excessive orthodontic force and also to explore the biological mechanism of the RANK/RANKL system in regulating odontoclastogenesis in root cementum. Thirty male Wistar rats were subjected to orthodontic force of 100 g to induce a mesially tipping movement of the left mandibular first molars. The contralateral molars served as intraindividual controls. The rats were sacrificed after 3, 7, or 10 days. The mandibular body surrounding the molars was harvested and serial sections of 6-μm thickness were cut. Immunohistochemical assays were conducted to localize the expression of RANK/RANKL proteins and histomorphological examination was undertaken to identify cellular response in cementum, periodontal ligament, and alveolar bone during root resorption. Root resorption in cementum occurred at the sites corresponding to compression of the periodontal ligament, indicated by increased numbers of multinucleated osteoclasts and odontoclasts. Immunoreaction against RANKL became stronger in osteoblasts, osteoclasts, odontoclasts, and fibroblasts of the periodontal ligament from Day 3 onwards. The number of positively immunoreactive cells against RANK also increased significantly over Days 3, 7, and 10 (p

For viral infectious diseases, reliable biomarkers capable of monitoring recovery and therapeutic effects and that simultaneously discriminate between viral and bacterial infection are necessary. In this study, by using flow-cytometric quantification system, Toll-like receptor 2 (TLR2) expression levels on monocytes of influenza patients (n=47) were compared with those of healthy volunteers (n=50). Subsequently, throughout their acute, convalescent and healed phases, TLR2, C-reactive protein (CRP), serum amyroid A (SAA), and neopterin levels were followed. Additionally, TLR2 levels in other viral infectious diseases were assayed. The results showed that TLR2 level in influenza patients was remarkably up-regulated in acute phase compared to healthy volunteers (p

A novel catalytic system using I2 and PhSiH3 for the intramolecular hydroalkoxylation of unactivated alkenes is described. NMR study indicated that in situ generated PhSiH2I is a possible active catalytic species. This catalytic system allows an efficient intramolecular hydroalkoxylation of phenyl-, trialkyl-, and 1,1-dialkyl-substituted alkenes as well as a variety of unactivated monoalkyl- and 1,2-dialkyl-substituted alkenes at room temperature. Mechanistic consideration based on significant experimental observations is also discussed.

Inhibitor development is one of the major problems in hemophilia patients. Whereas the inhibitor incidence in hemophilia A is estimated to be as high as 25-30%, it appears to be less frequent in hemophilia B, occurring in about 1-3% of hemophilia B patients. There are only a few case reports about immune tolerance induction (ITI) for hemophilia B patients. The present report describes ITI with rituximab in a patient with severe hemophilia B and inhibitor. The patient was diagnosed with severe hemophilia B at 9 months. He received prophylactic replacement therapy with plasma-derived factor IX (pd FIX). After 19 exposure days, inhibitor of factor IX was detected in his plasma, and replacement therapy was stopped. However, as he suffered from intracranial hemorrhage at the age of 1 year, he underwent first ITI at the age of 1 year. Unfortunately, this failed to reduce the level of the inhibitor, and this strategy was stopped after 2 years. Second ITI with pd FIX also failed. At the age of 14 years, ITI with rituximab was performed after obtaining informed consent. The patient received rituximab 375 mg/m once a week for four doses and received 40 u/kg of pd FIX every day. At 4 weeks after the start of ITI with rituximab, the level of the inhibitor of factor IX was diminished and was undetectable for 1 year after therapy. In this patient, ITI with rituximab was well tolerated and effective. This method should be considered for patients with hemophilia B and inhibitor.

Objective: Surgical treatment of thoracic aortic surgery in patients with coronary artery disease was investigated. Methods: Between 1990 and April 2003, 330 patients underwent elective thoracic aortic surgery. Fifty-six patients who underwent aortic root reconstruction were excluded and 274 patients were examined. Fifty-four (20%) patients showed concomitant coronary artery disease. Ten had undergone coronary revascularization previously; and 3 underwent coronary revascularization [2 coronary artery bypass grafting (CABG), 1 percutaneous transluminal coronary angioplasty (PTCA)] before aortic surgery. Twenty-three patients underwent elective CABG simultaneously and 2 patients had additional coronary artery bypass because of cardiac ischemia during operation. The number of patients who underwent thoracic aortic surgery including Asc Ao+AVR was 2, hemi arch 1, total arch 15, distal arch 5, distal arch+LV aneurysmectomy 1, and thoracoabdominal Ao 1. Two patients underwent coronary revascularization with arterial grafts and the others with SVG grafts. Results: There was one hospital death (4%). In patients without coronary bypass, 2 patients suffered cardiac ischemic events. Conclusion: Our thoracic aortic operations with concomitant CABG using SVG were overall successful. Our current strategies for thoracic aortic surgery in patients with concomitant coronary artery disease include conducting a dipyridamole myocardial perfusion-imaging test first in patients not at risk of coronary artery disease, and if the test is positive, coronary angiography is performed and aggressive coronary revascularization is conducted where possible.

Feeding trials were conducted to determine the availability of amino acid-chelated trace elements to rainbow trout. Three practical diets were supplemented with trace element mix either all from sulfates (Tr-Sf), Zn and Mn from sulfates added with Cu from amino acid chelates (Cu-Am) or a mixture of trace elements from amino acid chelates (Tr-Am). Rainbow trout weighing 1.11 g were fed the experimental diets for 15 weeks. Growth, feed gain ratio (FGR), tissue distribution, retention of the elements and plasma alkaline phosphatase (ALP) activity were compared between the treatments. Absorption of the elements was determined using larger fish of approximately 95 g fed the same experimental diets. Growth and FGR were not significantly influenced by the chemical form of the elements. The highest concentration of Cu was measured in the liver, whereas highest concentrations of Zn and Mn were in bone. Plasma ALP activity was significantly higher in the Tr-Am group. The absorption of elements from the Tr-Am diet was higher but not significantly different from the other two diets. These results suggest that trace elements from Tr-Am seem to be more available than from inorganic sources tested.

The object of this study was to develop a better catheter for selective cerebral perfusion during aortic arch operation. Flow through the catheter was evaluated in an in vitro study under 40 mmHg pressure at 25°C using 40% glycerin when the catheter was straight or right-angled with either a gentle or a sharp curve. Two catheters of 14, 16, or 18 French were connected with a Y-shaped tube, and the flow through each catheter was tested in the same way when the catheters were straight or right-angled. Moreover, we evaluated the operative outcome using this new catheter in 38 patients who underwent total arch replacement. The correlation between right radial artery pressure and catheter tip pressure was examined in 17 of these 38 patients. The difference in oxygenation between the right and left hemispheres was also exmained by two-channel nearinfrared spectroscopy. The results showed that flow through the catheter was almost identical, regardless of the type of its configuration. When two catheters of different sizes were connected with a Y-shaped tube, the total flow and flow ratio between the two catheters were also similar in both the straight and the right-angled configuration. As regards the clinical outcome, there were no in-hospital deaths, no permanent neurological dysfunction, and one temporary neurological dysfunction. Dissociations between right radial artery pressure and catheter tip pressure were seen in 3 of the 17 patients. No difference in oxygenation between the two hemispheres was found. We conclude that the new catheter provided an uncluttered operative field and may contribute to improved surgical results.

The objective of the present research was to compare the availability of zinc in the form of organic zinc, zinc amino acid chelate, with in the form of sulfate in growing pigs. Twenty-five pigs of 25 d-old were divided into 5 groups. Five pigs of each group were fed a basal diet which was a commercial ration without supplying zinc or diets added 25, 50 or 100mg/kg dry matter zinc in the form of amino acid chelate, or 100mg/kg dry matter zinc in the form of sulfate for 30d. The basal diet contained 47mg/kg of zinc and did not satisfy its requirement for the pigs. The diets contained twice more calcium and 15 times more copper than the requirements for the pigs. Femoral and serum zinc concentrations were increased with supplying zinc amino acid chelate and were significantly higher in pigs given the organic zinc than in those given the inorganic zinc at the level of 100mg/kg diet. Zinc solubility in ileal digesta was gradually increased with supplying the organic zinc. Additionally, zinc solubility tended to be higher in the pigs given organic zinc than in those given the same amount of inorganic zinc. These results suggested that the availability of organic zinc was higher than inorganic zinc in the pigs fed a high calcium and copper diet, which, at least partly, resulted from the higher solubility of organic zinc in the ileum.

Interleukin (IL)-17 is an important mediator of orthodontically induced inflammatory root resorption (OIIRR). However, its role in the dental pulp (DP) has not been studied. The aim of this study was to investigate, using an atopic dermatitis (AD) model, how IL-17 contributes to OIIRR in DP. Atopic dermatitis is the most common IL-17-associated allergic disease. Atopic dermatitis model mice (AD group) and wild-type mice (control group) were subjected to an excessive orthodontic force. The localization of T-helper (Th)17 cells, IL-17, IL-6, and keratinocyte chemoattractant (KC; an IL-8-related protein in rodents) were determined in DP. In addition, CD4+ T cells, including IL-17 production cells, were obtained from patients with AD and from healthy donors, and the effects of IL-17 on the production of IL-6 and IL-8 were investigated using a co-culture of CD4+ T cells with human dental pulp (hDP) cells stimulated with substance P (SP). Immunoreactivity for Th17 cells, IL-17, IL-6, and KC was increased in DP tissue subjected to orthodontic force in the AD group compared with DP tissue subjected to orthodontic force in the control group. The cells obtained from the AD patients displayed increased IL-6 and IL-8 production. These results suggest that IL-17 may aggravate OIIRR in DP.

Bilirubin can prevent oxidation of low-density lipoprotein (LDL) and may protect against atherosclerosis and coronary heart disease (CHD). The goal of this study was to characterize the relationship between bilirubin and CHD through measurements of bilirubin concentration, coronary endothelial function, and markers of oxidative stress, inflammation, and lipid/glucose metabolism. The study population consisted of 141 patients without CHD who underwent Doppler flow study. Vascular reactivity was examined by intracoronary administration of papaverine, acetylcholine (ACh) and nitroglycerin using a Doppler guide wire. Serum bilirubin, high-sensitivity C-reactive protein (hsCRP), malondialdehyde-modified LDL, LDL cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting plasma glucose (FPG), and immunoreactive insulin were also measured. Homeostasis model assessment insulin resistance index and estimated glomerular filtration rate (eGFR) were calculated. Univariate analysis revealed that both percent change in coronary blood flow (CBF) and coronary artery diameter induced by ACh correlated positively with log-transformed bilirubin (r = 0.22, P < 0.05; r = 0.20, P < 0.05, respectively). Percent change in CBF in response to ACh correlated positively with eGFR (r = 0.24, P < 0.05) and correlated inversely with age, LDL-C, and log-transformed FPG (r = -0.24, P < 0.05; r = -0.17, P < 0.05, r = -0.22, P < 0.05, respectively). Multivariate analysis revealed that log-transformed bilirubin was the only independent predictor of percent change in CBF in response to ACh. Multivariate analysis revealed that log-transformed hsCRP and HDL-C were independent predictors of log-transformed bilirubin. These results suggest that a high level of bilirubin is associated with favorable coronary endothelial function, which may be mediated via the effect of bilirubin on inflammation and HDL-C.

Aim: Bilirubin has antioxidant properties and may protect against atherosclerosis and coronary heart disease (CHD). Further, in patients with metabolic syndrome, hyperbilirubinemia is associated with attenuation of insulin resistance. The aim of the present study was to determine the relationship between serum bilirubin concentration and coronary endothelial function in overweight patients.Methods: The study population consisted of 107 patients without CHD who underwent coronary flow studies. Vascular reactivity was examined by intra-coronary administration of papaverine and nitroglycerin. Coronary endothelial function was evaluated by assessing the change in coronary artery diameter to papaverine [percent change in flow-mediated dilatation (%FMD)] and nitroglycerin (%NTG). Serum total bilirubin, high-sensitivity C-reactive protein (hs-CRP), high density lipoprotein-cholesterol (HDL-C), fasting plasma glucose and immunoreactive insulin levels were also measured, and the homeostasis model assessment insulin resistance (HOMA-IR) index was calculated. Patients were divided into two groups according to body mass index (BMI): an overweight group (BMI ≥ 25; n = 36) and a normal weight group (BMI < 25; n = 71).Results: In the overweight group, univariate analysis revealed that log-transformed total bilirubin was positively correlated with %FMD and HDL-C (r = 0.38, p< 0.05; r = 0.30, p < 0.05, respectively) and was inversely correlated with log-transformed hs-CRP and HOMA-IR (r = −0.45, p < 0.01; r = −0.45, p< 0.05, respectively). Multivariate analysis revealed that log-transformed hs-CRP was the only independent predictor of log-transformed total bilirubin (p< 0.05).Conclusions: These results suggest that a high bilirubin level was associated with favorable coronary endothelial function in overweight patients. Further, the anti-inflammatory effects of bilirubin may mediate this effect.

Background and purpose We have reported previously that Waon therapy improves cardiac and vascular function, and prognosis of patients with chronic heart failure (CHF). CHF is characterized by generalized sympathetic activation and parasympathetic withdrawal. The purpose of this study was to evaluate the effect of Waon therapy on autonomic nervous activity in patients with CHF. Methods and subjects Fifty-four patients with CHF, who were receiving conventional therapy for CHF, were divided into Waon therapy and control groups. In the Waon therapy group, 27 patients were treated with medication and Waon therapy. In the control group, 27 patients were treated with only conventional CHF therapy. Cardiac function including cardiac output (CO) and left ventricular ejection fraction (LVEF) was evaluated by echocardiography. The heart rate variability, such as the coefficient of variation of RR intervals (CVRR), the low-frequency (LF) component, high-frequency (HF) component, the LF norm [LF/(LF+HF)], and HF norm [HF/(LF+HF)], were measured at admission and 4 weeks after treatment. Results Echocardiography demonstrated that CO and LVEF significantly increased after 4 weeks in the Waon therapy group, but did not change in the control group. In the Waon therapy group, CVRR, HF, and HF norm significantly increased 4 weeks after Waon therapy. In addition, the LF/HF ratio and LF norm significantly decreased 4 weeks after Waon therapy. In contrast, these parameters remained unchanged in the control group. Moreover, the HF and HF norm were significantly higher, and the LF/HF ratio and LF norm were significantly lower after 4 weeks of Waon therapy group than after 4 weeks of only conventional therapy. Conclusions Waon therapy improved cardiac function and autonomic nervous activity by increasing parasympathetic and decreasing sympathetic nervous activity in patients with CHF.

Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns to initiate an innate immune response. We previously reported upregulation of TLR2 expression level on monocytes of stable angina pectoris patients with significant coronary artery disease (CAD) relative to control patients without significant CAD. In this study we aimed to determine whether high level of Toll-like receptor 2 (TLR2) is a risk factor for atherogenesis, independent of established risk factors including smoking, diabetes mellitus (DM), hypertension (HT), and hyperlipidemia (HL).TLR2 expression level on circulating monocyte surfaces was measured by using our developed flow cytometry assay. Patients were classified into two groups: "Arteriosclerotic disease" group (n=108) and "Control" group (n=70). Patients of the first group had arteriosclerotic disease such as CAD, aortic aneurysm, or peripheral arterial disease (PAD). The "Control" group was sex- and age-matched to the "Arteriosclerotic disease" group.TLR2 expression was significantly higher in the "Arteriosclerotic disease" group than in the "Control" group (p0.001). Multivariate ordinal logistic regression analysis was performed; other known risk factors, which were represented to two nominal score points, 0 or 1, for patients with and without it, respectively, and TLR2 level, which was treated as a metric variable. DM (p=0.002), HT (p=0.001), HL (p0.001), and TLR2 level (p0.001) were identified as significant contributors for arteriosclerotic disease.High TLR2 expression level on monocytes may be an independent risk factor for atherogenesis.

An unhealthy lifestyle can increase the risk of cardiovascular disease. However, the mechanism by which lifestyle influences the development of cardiovascular disease remains unclear. Since coronary endothelial function is a predictor of cardiovascular prognosis, the goal of this study was to characterize the effect of enjoying hobbies on coronary endothelial function and cardiovascular outcomes. A total of 121 consecutive patients (76 men, 45 women) with almost normal coronary arteries underwent Doppler flow study of the left anterior descending coronary artery following sequential administration of papaverine, acetylcholine, and nitroglycerin. On the basis of responses to questionnaires, patients were divided into two groups; the Hobby group (n = 71) who enjoyed hobbies, and the Non-hobby group (n = 50) who had no hobbies. Cardiovascular outcomes were assessed at long-term follow-up using medical records or questionnaire surveys for major adverse cardiovascular events (MACE).The average follow-up period was 916 +/- 515 days. There were no significant differences in demographics when comparing the two groups. The percent change in coronary blood flow and coronary artery diameter induced by acetylcholine was significantly greater in the Hobby group than in the Non-hobby group (49% +/- 77% vs 25% +/- 37%, P0.05, 4% +/- 13% vs -3% +/- 20%, P0.05, respectively). The MACE rate was significantly lower in the Hobby group than in the Non-hobby group (P0.01). Enjoyment of hobbies was the only independent predictor of MACE (odds ratio 8.1 [95% confidence interval 1.60, 41.90], P = 0.01) among the variables tested. In the early stages of arteriosclerosis, enjoying hobbies may improve cardiovascular outcomes via its favorable effects on coronary endothelial function.

A 39-year-old woman had undergone mitral valve replacement (MVR) (29-mm Björk-Shiley Delrin disk) at 6 years of age. Severe mitral regurgitation, aortic regurgitation, and left ventricular dilatation were detected by echocardiography in October 2006, and MVR (ON-X 25 mm) and aortic valve replacements (St. Jude Medical Regent, 21 mm) were performed in December. The Delrin disk of the previous prosthetic valve, located at the position of the mitral valve, was markedly abraded, broadening the clearance from the valve seat. The postoperative course was smooth without complications, and the patient was discharged, walking by herself, on day 19 after surgery. A Delrin disk was used for the tilting valve in early Björk-Shiley valves, but has been replaced by pyrolytic carbon because of problems with durability of the Delrin material. Follow-ups of patients who have undergone procedures using Delrin disks ares necessary, with consideration of valve replacement.

A 56-year-old woman was seen who had been under hemodialysis treatment. In September 2003, the patient was sent to our hospital with fever and dyspnea, and artificial respiration was initiated. Bronchoscopy detected stenosis due to compression of the bronchus. Contrast computed tomography and angiography detected a pseudoaneurysm of the right common carotid artery. We performed emergency excision of the mycotic pseudoaneurysm, which was closed with an autologous pericardial patch. We also performed median sternotomy to obtain an adequate surgical view. A perfusion tube was inserted into the internal carotid artery. The inflammatory findings and dyspnea resolved postoperatively.