Association of poor oral health with increased incidence of dysphagia and impaired improvement in nutritional status among patients with acute heart failure: a prospective cohort study.

AIMS: This study aimed to clarify the association between oral health and the incidence of dysphagia as well as the recovery of nutritional status and improvement of dysphagia in hospitalized patients with acute heart failure. METHODS: Hospitalized patients with AHF were prospectively enrolled. Oral health was evaluated using the Japanese Version of the Oral Health Assessment Tool (OHAT-J) after circulation dynamics improved (defined as baseline), and participants were classified into good and poor oral health groups (OHAT-J 0-2 and ≧ 3, respectively). The primary outcome measure was the incidence of dysphagia evaluated using the Food Intake Level Scale (FILS) at baseline. Secondary outcome measures were nutritional status and FILS score at discharge. Nutritional status was assessed using the Mini Nutritional Assessment Short Form (MNA-SF). Univariate and multivariate logistic regression analyses were used to determine the association between oral health and the study outcomes. RESULTS: Of the 203 recruited patients (mean age, 79.5 years; 50.7% female), 83 (40.9%) were in the poor oral health group. Participants with poor oral health were significantly older, had lower skeletal muscle mass and strength, lower nutrient intake and nutritional status, worse swallowing status, as well as lower cognitive level, and physical function than those with good oral health. In multivariate logistic regression analyses, baseline poor oral health was significantly associated with the incidence of dysphagia (odds ratio = 1.036, P = 0.020), as well as with the improvement in nutritional status (odds ratio = 0.389, P = 0.046) and dysphagia (odds ratio = 0.199, P = 0.026) at discharge. CONCLUSIONS: Poor baseline oral health was associated with the incidence of dysphagia, as well as with the lack of improvement in nutritional status and dysphagia in patients with acute heart failure.

Association of resting energy expenditure-based energy intake sufficiency with functional recovery, dysphagia, and 1-year mortality following heart failure: A prospective observational study.

AIM: Evidence for the influence of resting energy expenditure (REE)-based energy intake on the outcomes of patients with heart failure (HF) is scarce. This study evaluates the relationship between REE-based energy intake sufficiency and clinical outcomes in hospitalized HF patients. METHODS: This prospective observational study included newly admitted patients with acute HF. REE was measured using indirect calorimetry at baseline and total energy consumption (TEE) was calculated by multiplying REE with activity index. Energy intake (EI) was recorded, and the patients were classified into two groups, namely, the energy intake sufficiency (i.e., EI/TEE ≥1) and energy intake deficiency groups (i.e., EI/TEE <1). The primary outcome was the performance of activities of daily living, assessed using the Barthel Index, at discharge. Other outcomes included dysphagia at discharge and all-cause 1-year mortality following discharge. Dysphagia was defined as a Food Intake Level Scale (FILS) score of <7. Multivariable analyses and Kaplan-Meier estimates were used to determine the association of energy sufficiency both at baseline and at discharge with the outcomes of interest. RESULTS: The analysis included 152 patients (mean age, 79.7 years; 51.3% women); of them, 40.1% and 42.8% had inadequate energy intake both at baseline and at discharge, respectively. In multivariable analyses, energy intake sufficiency at discharge was significantly associated with the BI (ß = 0.136, p = 0.002) and FILS score (odds ratio = 0.027, p < 0.001) at discharge. Moreover, energy intake sufficiency at discharge was associated with 1-year mortality after discharge (p < 0.001). CONCLUSION: Adequate energy intake during hospitalization was associated with improved physical and swallowing functions and 1-year survival in HF patients. Adequate nutritional management is essential for hospitalized HF patients, suggesting that adequate energy intake may lead to optimal outcomes.

Role of systemic inflammation in functional recovery, dysphagia, and 1-y mortality in heart failure: A prospective cohort study.

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 (ß = -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.

Incidence of Dysphagia and Its Association With Functional Recovery and 1-Year Mortality in Hospitalized Older Patients With Heart Failure: A Prospective Cohort Study.

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 (ß= -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.

Dysphagia is associated with poor physical function in patients with acute heart failure: a prospective cohort study.

BACKGROUND: 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. AIMS: This study examined the association of dysphagia and physical function in patients undergoing cardiac rehabilitation following heart failure. METHODS: 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. RESULTS: Of the 149 patients, 14 (9.4%) had dysphagia at the time of stabilization of heart failure. Patients with dysphagia (FILS score < 7) were significantly older, more demented, exhibited lower muscle mass and strength, walked shorter distances, and had lower energy and protein intakes, longer length of stay, and lower BI scores (all, p < 0.05) compared to those without dysphagia. Multiple regression analyses showed that FILS score was independently associated with BI at discharge (ß = 0.364, p < 0.001). CONCLUSIONS: Dysphagia was associated with declined physical function in patients undergoing cardiac rehabilitation following heart failure. Early detection and management of dysphagia can promote timely functional recovery in these patients.

Risk of malnutrition is associated with poor physical function in patients undergoing cardiac rehabilitation following heart failure.

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 < 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 (ß = 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. CONCLUSIONS: 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.

Long-term outcome of renal function in children after stem cell transplantation measured by estimated glomerular filtration rate.

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 (<90 ml/min/1.73 m2 ) post SCT. Cumulative incidence of low eGFR was 25.8 ± 2.0%. Nine (10.6%) patients had a low eGFR pre-SCT. However, pre- and post-SCT incidence of low eGFR were not correlated. Meanwhile, only two patients (2.4%) exhibited severe renal dysfunction, with eGFRs < 60 ml/min/1.73 m2 . Independent risk factors for low eGFR were solid tumor and use of fludarabine. Moreover, age at SCT ≥ 7 years was also a long-term post-SCT risk factor for low eGFR in all patients. CONCLUSION: Independent post-SCT long-term risk factors for low eGFR in children were solid tumor and use of fludarabine. Moreover, age at SCT ≥ 7 years was a post-SCT long-term risk factor for low eGFR across all patients.

Extrarenal Nephroblastoma of the Retroperitoneal Space in Children: A Case Report and Review of the Literature.

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%).

Reagents for diverse iodosilane-mediated transformations.

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.

Intramolecular Hydroalkoxylation of Unactivated Alkenes Using Silane-Iodine Catalytic System.

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.

Successful treatment of immune tolerance induction with rituximab in a patient with severe hemophilia B and inhibitor.

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.

Interleukin-17/T-helper 17 cells in an atopic dermatitis mouse model aggravate orthodontic root resorption in dental pulp.

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.

Atrial fibrillation-induced endothelial dysfunction improves after restoration of sinus rhythm.

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 6 months 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: Loge 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<0.01). Multivariate logistic regression analysis revealed that persistent AF was the only independent predictor of impaired endothelial function defined as loge RHI<0.6 (odds ratio, 4.96; 95% CI, 1.2 to 21.3; p<0.05). Loge RHI was significantly higher after ABL than before ABL (0.53±0.20; 0.73 ± 0.25; p<0.01) in the day 1-restored SR group. Loge 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.

Characterization of the effect of serum bilirubin concentrations on coronary endothelial function via measurement of high-sensitivity C-reactive protein and high-density lipoprotein cholesterol.

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.

Highly sensitive cardiac troponin T in heart failure: comparison with echocardiographic parameters and natriuretic peptides.

BACKGROUND: Circulating cardiac troponin T is a marker of cardiomyocyte injury, and predicts adverse outcomes in patients with chronic heart failure. However, the significance of highly sensitive cardiac troponin T (hs-TnT) in cardiac dysfunction remains uncertain. The purpose of this study is to evaluate the correlation between hs-TnT and echocardiographic parameters or natriuretic peptides in patients with heart failure. METHODS AND RESULTS: We analyzed 283 consecutive out- or in-patients who had B-type natriuretic peptide (BNP) ≥20 pg/mL and were examined by echocardiography (mean age 66.5±13.9 years old; 159 males). Hs-TnT, BNP, N-terminal pro-BNP (NT-proBNP), and creatinine levels were measured simultaneously. LVEDD (left ventricular end-diastolic dimension), LVEF (left ventricular ejection fraction), E', E/E', left ventricular (LV) Tei index, and right ventricular (RV) Tei index were determined with echocardiography. The linear regression analyses demonstrated that loghs-TnT correlated with LVEDD (R=0.242, p<0.0001), LVEF (R=-0.369, p<0.0001), E' (R=-0.447, p<0.0001), E/E' (R=0.364, p<0.0001), LV Tei index (R=0.303, p<0.0001), RV Tei index (R=0.443, p<0.0001), and estimated glomerular filtration rate (eGFR) (R=-0.489, p<0.0001). Using multiple variable regression analysis, loghs-TnT independently correlated with LVEF, E/E', RV Tei index, and eGFR. Furthermore, loghs-TnT significantly correlated with logBNP (R=0.567, p<0.0001) or logNT-proBNP (R=0.647, p<0.0001). Multiple variable regression analysis demonstrated that loghs-TnT independently correlated with logBNP, age, and eGFR, or with logNT-proBNP, age, sex, and eGFR. CONCLUSIONS: The hs-TnT correlated with cardiac dysfunction evaluated by echocardiography and natriuretic peptides in patients with heart failure. The elevation of hs-TnT levels in heart failure may represent cardiac dysfunction due to minor and ongoing myocardial injury.

Relationship between bilirubin concentration, coronary endothelial function, and inflammatory stress in overweight patients.

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.

Improvement of autonomic nervous activity by Waon therapy in patients with chronic heart failure.

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.

Expressions of RANKL/RANK and M-CSF/c-fms in root resorption lacunae in rat molar by heavy orthodontic force.

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.

Effect of Waon therapy on oxidative stress in chronic heart failure.

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<0.001; BNP, 402±221 to 225±137pg/ml, P<0.001), and the nitric oxide metabolites increased (71.2±35.4 to 92.0±40.5mmol/L, P<0.05). In contrast, none of these variables changed over the 4-week interval in the control group. Furthermore, animal experiments were performed using TO-2 cardiomyopathic hamsters. On immunohistochemistry, cardiac expression of 4-hydroxy-2-nonenal, a marker of oxidative stress, was decreased in the 4-week Waon therapy compared to untreated hamsters. On Western blotting, cardiac expressions of heat shock protein (HSP) 27, manganese superoxide dismutase and HSP32, which reduce oxidative stress, were significantly upregulated in the 4-week Waon therapy compared to untreated hamsters. CONCLUSIONS: Waon therapy decreases oxidative stress in patients and hamsters with heart failure.

Waon therapy mobilizes CD34+ cells and improves peripheral arterial disease.

BACKGROUND: We 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. METHODS: 21 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. RESULTS: The 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 ± 17.7 µmol/ml, p<0.05), but not in the control group (34.4 ± 9.4 to 38.3 ± 8.8 µmol/ml). CONCLUSION: Waon therapy mobilized circulating endothelial progenitor cells and improved limb ischemia in patients with PAD. Waon therapy is a highly promising therapy for patients with PAD.