Ryoichi Nagatomi

Impact of Nocturia on Bone Fracture and Mortality in Older Individuals: A Japanese Longitudinal Cohort Study

PURPOSE We evaluated the association of nocturia with fracture and death in a large, community based sample of Japanese individuals 70 years old or older. MATERIALS AND METHODS The baseline in this population based study was determined in 2003 by an extensive health interview with each participant. In this study we followed 784 individuals with a mean ± SD age of 76.0 ± 4.6 years (range 70 to 97). Information on mortality and fracture during the study period was provided by the National Health Insurance system and details on fractures were collected from medical records. We compared the risk of bone fracture and death with or without nocturia in a multivariate Cox proportional hazard model. RESULTS Nocturia (2 or greater voids per night) was present in 359 of the 784 participants (45.7%). Fracture was observed in 41 cases, including 32 fall related cases. For all fractures and fall related fractures with nocturia the HR was 2.01 (95% CI 1.04-3.87) and 2.20 (95% CI 1.04-4.68, each p = 0.04). Death occurred in 53 cases. The mortality rate in individuals with nocturia was significantly higher than in those without nocturia. For mortality in patients with nocturia the age-gender adjusted HR was 1.91 (95% CI 1.07-3.43, p = 0.03). Even when further adjusted for diabetes, smoking status, history of coronary disease, renal disease and stroke, tranquilizers, hypnotics and diuretics, the positive relationship was unchanged (HR 1.98, 95% CI 1.09-3.59, p = 0.03). CONCLUSIONS During a 5-year observation period elderly individuals with nocturia were at greater risk for fracture and death than those without nocturia.

Myofibers Express IL-6 After Eccentric Exercise

Background Interleukin (IL)-6 is locally produced in skeletal muscles and shows a remarkable increase in plasma after eccentric exercises. Objective To elucidate the cell types in the muscles responsible for IL-6 production after eccentric exercises. Study Design Controlled laboratory study. Methods An eccentric contraction model was made using electrical stimulation. The authors investigated the muscle damage and regeneration processes after eccentric exercises histologically, and the cell types expressing IL-6 and its subcellular compartimentalization with time immunohistochemically after eccentric exercises. Results Swollen myofibers were detected from 8 hours to 3 days after exercises. Disrupted myofibers were detected from 24 hours to 7 days, with a peak of 3 days. IL-6 was detected only in the cytoplasm of myofibers until 12 hours; thereafter, it was found in the inflammatory cells and proliferating satellite cells as well. The swollen myofibers were negatively stained for IL-6. The positive ratios of IL-6 in myofibers immediately increased after exercises, peaked in 12 hours, and then decreased. Conclusions After eccentric exercises, IL-6 expression increased in myofibers preceding the disruption of myofibers. IL-6 might be closely related to muscle damage caused by strenuous exercises.

Green tea consumption is associated with depressive symptoms in the elderly

BACKGROUND Green tea is reported to have various beneficial effects (eg, anti-stress response and antiinflammatory effects) on human health. Although these functions might be associated with the development and progression of depressive symptoms, no studies have investigated the relation between green tea consumption and depressive symptoms in a community-dwelling population. OBJECTIVE The aim of this study was to investigate the relations between green tea consumption and depressive symptoms in elderly Japanese subjects who widely consumed green tea. DESIGN We conducted a cross-sectional study in 1058 community-dwelling elderly Japanese individuals aged >or=70 y. Green tea consumption was assessed by using a self-administered questionnaire, and depressive symptoms were evaluated by using the 30-item Geriatric Depression Scale with 2 cutoffs: 11 (mild and severe depressive symptoms) and 14 (severe depressive symptoms). If a participant was consuming antidepressants, he or she was considered to have depressive symptoms. RESULTS The prevalence of mild and severe and severe depressive symptoms was 34.1% and 20.2%, respectively. After adjustment for confounding factors, the odds ratios (95% CI) for mild and severe depressive symptoms when higher green tea consumption was compared with green tea consumption of <or=1 cup/d were as follows: 2-3 cups green tea/d (0.96; 95% CI: 0.66, 1.42) and >or=4 cups green tea/d (0.56; 95% CI: 0.39, 0.81) (P for trend: 0.001). Similar relations were also observed in the case of severe depressive symptoms. CONCLUSION A more frequent consumption of green tea was associated with a lower prevalence of depressive symptoms in the community-dwelling older population.

Factors associated with suicidal ideation in an elderly urban Japanese population: A community‐based, cross‐sectional study

Abstract  The objective of the present study was to evaluate the association between suicidal ideation and potentially related factors in an elderly urban Japanese population. This was a community‐based, cross‐sectional study. Urban community residents aged 70 years or more were interviewed regarding suicidal ideation and sociodemographic and health‐related variables. Subjects with depressive symptoms underwent further evaluation by psychiatrists using criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. Associations were evaluated using univariate and multivariate logistic regression analyses. Of the 1145 eligible participants, 52 (4.5%) reported thoughts of suicide. Of 143 subjects with depressive symptoms (Geriatric Depression Scale, 14+), 22 (15.4%) reported suicidal ideation over a 2‐week period. After controlling for depressive symptoms, lack of social support and impaired instrumental activities of daily living were significantly associated with thoughts of suicide. After controlling for the potentially associated factors detected in the univariate analysis, depressive symptoms were strongly associated with thoughts of suicide. In the elderly with depressive symptoms, mental disorders, including depressive and alcohol‐related disorders, were significantly associated with suicidal ideation over a 2‐week period. In the urban community setting, screening for lack of social support, impaired instrumental activities of daily living, and depressive symptoms, followed by diagnostic evaluation for mental disorders, particularly for depressive syndromes and alcohol‐related disorders, may provide a practical and effective means of identifying elders at high risk of suicide.

Clarithromycin Inhibits Type A Seasonal Influenza Virus Infection in Human Airway Epithelial Cells

Human influenza viruses attach to sialic acid with an α2,6linkage (SAα2,6Gal) on the airway epithelial cells, and the entry of the viruses into the cells and uncoating of the viruses require low pH of endosomes. Bafilomycin A1, a macrolide antibiotic and a specific inhibitor of vacuolar H+-ATPase, inhibits growth of type A and type B human influenza viruses in Madin-Darby canine kidney cells. However, the inhibitory effects of clinically used macrolide antibiotics on influenza virus infection in human airways have not been studied. To examine the effects of clarithromycin on seasonal human influenza virus infection, cultured human tracheal epithelial cells were infected with type A influenza virus (H3N2). Influenza virus infection increased viral titers and the content of cytokines, including interleukin (IL)-1β and IL-6, in supernatant fluids, and viral RNA in the cells. Clarithromycin reduced viral titers and the content of cytokines in supernatant fluids, viral RNA in the cells, and the susceptibility to virus infection. Clarithromycin reduced the expression of SAα2,6Gal, a receptor for human influenza virus, on the mucosal surface of human tracheae, and the number and fluorescence intensity of acidic endosomes in the cells from which viral ribonucleoproteins enter into the cytoplasm. Furthermore, clarithromycin reduced nuclear factor-κB (NF-κB) proteins, including p50 and p65, in the nuclear extracts. These results suggest that clarithromycin may inhibit seasonal human influenza virus infection by reducing SAα2,6Gal partly through the inhibition of NF-κB, and increasing pH in endosomes in airway epithelial cells. Clarithromycin may modulate airway inflammation in influenza virus infection.

Notch2 negatively regulates myofibroblastic differentiation of myoblasts.

Myofibroblasts are one of the key cellular components involved in fibrosis of skeletal muscle as well as in other tissues. Transforming growth factor‐β1 (TGF‐β1) stimulates differentiation of mesenchymal cells into myofibroblasts, but little is known about the regulatory mechanisms of myofibroblastic differentiation. Since Notch2 was shown to be downregulated in TGF‐β1‐induced non‐muscle fibrogenic tissue, we investigated whether Notch2 also has a distinctive role in myofibroblastic differentiation of myogenic cells induced by TGF‐β1. TGF‐β1 treatment of C2C12 myoblasts led to expression of myofibroblastic marker α‐smooth muscle actin (α‐SMA) and collagen I with concomitant downregulation of Notch2 expression. Overexpression of active Notch2 inhibited TGF‐β1‐induced expression of α‐SMA and collagen I. Interestingly, transient knockdown of Notch2 by siRNA in C2C12 myoblasts and primary cultured muscle‐derived progenitor cells resulted in differentiation into myofibroblastic cells expressing α‐SMA and collagen I without TGF‐β1 treatment. Furthermore, we found Notch3 was counter‐regulated by Notch2 in C2C12 cells. These findings suggest that Notch2 is inhibiting differentiation of myoblasts into myofibroblasts with downregulation of Notch3 expression. J. Cell. Physiol. 210: 358–369, 2007.

Home blood pressure is associated with depressive symptoms in an elderly population aged 70 years and over: a population-based, cross-sectional analysis.

Although several epidemiologic studies have assessed the relationship between low blood pressure and depressive symptoms in geriatric populations, the results have been inconsistent. Because the white-coat phenomenon is observed frequently in patients with depressive symptoms, we have considered that blood pressure measured in nonmedical settings is important in assessing the relationship between blood pressure and depressive symptoms among the geriatric population. The aim of this study was to investigate the relationships between home blood pressure and depressive symptoms in a community-based elderly population aged 70 years and over. We analyzed a cross-sectional survey comprised of 888 community-dwelling Japanese aged 70 years and older. Blood pressure was self-measured at home, and depressive symptoms were evaluated using the 30-item Geriatric Depression Scale (GDS 30) with a cutoff point of 11. The prevalence of depressive symptoms was 34.8%. For all subjects, after adjustments for potentially confounding factors, the odds ratios of having depressive symptoms by increasing quartiles of systolic blood pressure of subjects not taking antihypertensive drugs to subjects taking them were 1.00, 0.97, 0.88, 0.59, and 0.70. Statistically significant inverse relationships were observed in subjects not taking antihypertensive drugs. No apparent association between diastolic blood pressure and depressive symptoms was observed in any subjects or in a stratified analysis of antihypertensive drug use. In this study, a higher home systolic blood pressure was independently and continuously related to a lower prevalence of depressive symptoms in participants not using antihypertensive medication. Further study is required to clarify the causality of this relationship.

Oral Health Behavior and Metabolic Syndrome and Its Components in Adults

Inflammation has been strongly related to metabolic syndrome (MetS). Periodontal disease is the most common chronic infection in adults. We investigated a cross-sectional (n = 925) and 3-year longitudinal (n = 685) relationship between the daily frequency of toothbrushing and MetS. In the cross-sectional analysis, the prevalence of MetS was 15.7%. After adjustment for potential confounding factors (including all lifestyle factors), the odds ratios (95% confidence interval [CI]) of having MetS in those who brushed 2 times/day and ≥ 3 times/day were 0.71 (0.48-1.05) and 0.47 (0.24-0.92), respectively, as compared with ratios in those with a toothbrushing frequency of ≤ 1 time/day. Increasing toothbrushing frequency tended to relate inversely to hypertriglyceridemia and high-sensitivity C-reactive protein. In the longitudinal analysis, 99 participants were newly diagnosed with MetS. The adjusted odds ratios (95% CI) of the MetS in participants who brushed 2 times/day and ≥ 3 times/day as compared with participants who brushed ≤ 1 time/day were 0.80 (0.49-1.31) and 0.43 (0.19-0.97), respectively. The frequency of toothbrushing was related inversely only to hypertriglyceridemia, consistent with the cross-sectional analysis. This study found that more frequent toothbrushing is related to a lower prevalence and incidence of MetS. These results suggest that more frequent toothbrushing may contribute to the prevention of MetS due to the inflammation/triglyceride pathway.

Macrolide antibiotics inhibit respiratory syncytial virus infection in human airway epithelial cells

To examine the effects of macrolide antibiotics on RS virus infection in airways, human tracheal epithelial cells were pre-treated with bafilomycin A(1) and clarithromycin, and infected with RS virus. Viral titers in supernatant fluids and RNA of RS virus, and concentrations of cytokines in supernatant fluids, including interleukin-6 increased with time after infection. Bafilomycin A(1) and clarithromycin reduced viral titers in supernatant fluids of RS virus, RNA of RS virus, the susceptibility to RS virus infection, and concentrations of cytokines induced by virus infection. N-acetyl-S-geranylgeranyl-L-cysteine, an inhibitor for a small GTP binding protein of RhoA, isoform A of the Ras-homologus (Rho) family, an active form of which is associated with RS virus infection via binding to its fusion protein (F protein), reduced viral titers in supernatant fluids and RNA of RS virus. Bafilomycin A(1) and clarithromycin inhibited RhoA activation induced by lysophosphatidic acid in the cells. Fasudil, an inhibitor of Rho kinase, also reduced viral titers in supernatant fluids and RNA of RS virus. These findings suggest that macrolide antibiotics may inhibit RS virus infection, partly through the reduced expression of F protein receptor, activated RhoA, and the inhibition of subsequent Rho kinase activation in human airway epithelial cells.

Knockdown of hypoxia-inducible factor-1α by siRNA inhibits C2C12 myoblast differentiation

We analyzed the role of Hypoxia‐inducible factor (HIF)‐1α in myoblast differentiation by examining the expression and regulation of HIF‐1α in proliferating and differentiating C2C12 myoblast, and by knocking down HIF‐1α of C2C12 myoblasts with small interfering RNA (siRNA), given that HIF‐1α has been shown to be involved in differentiative process in non‐muscle tissues. Although HIF‐1α mRNA was constantly expressed in C2C12 myoblasts both under growth and differentiating phase, HIF‐1α protein was hardly detectable in the growth phase but became detectable only during myogenic differentiation even under normoxia. During early stage of C2C12 myogenesis, HIF‐1α accumulated in the nuclei of myogenin‐positive myoblasts. The inhibition of proteasome in the growth phase led to HIF‐1α protein accumulation, whereas in the differentiation phase the inhibition of Hsp90, which stabilizes HIF‐1α, suppressed HIF‐1α accumulation. Therefore, we suggest that the level of HIF‐1α protein expression is regulated by a proteasome‐and chaperon‐dependent pathway in C2C12 myoblast. Knockdown of HIF‐1α effectively blocked myotube formation and myosin heavy chain (MHC) expression. Finally, HIF‐1α expression in vivo was confirmed in the regenerative muscle tissue of mice after eccentric exercise. We conclude that HIF‐1α is required for C2C12 myogenesis in vitro, and suggest that HIF‐1α may have an essential role in regenerative muscle tissue in vivo. J. Cell. Biochem. 98: 642–649, 2006.