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Aim: To elucidate mechanisms by which mineral trioxide aggregate (MTA) suppresses pro‐inflammatory cytokine mRNA expression in lipopolysaccharide (LPS)‐stimulated RAW264.7 macrophages. Methodology: Mineral trioxide aggregate extracts were prepared by immersing set ProRoot MTA in culture medium. RAW264.7 cells were cultured in the presence of LPS and MTA extracts. mRNA expression levels of interleukin (IL)‐1α, IL‐6, early growth response 2 (Egr2), suppressor of cytokine signalling 3 (Socs3) and IL‐10 were quantified with reverse transcription‐quantitative polymerase chain reaction. Phosphorylation of nuclear factor‐kappa B (NF‐κB) p65 in RAW264.7 cells was analysed by Western blotting. Intracellular calcium imaging was performed with Fluo‐4 AM. The activity of nuclear factor of activated T cells (NFAT) was determined by luciferase assays. Enforced expression and silencing of Egr2 in RAW264.7 cells were carried out using an expression vector and specific RNAi, respectively. In vivo kinetics of Egr2+ cells in MTA‐treated rat molar pulp tissues were examined using immunohistochemistry. Data were analysed by one‐way analysis of variance, followed by the Tukey–Kramer test (P < 0.05). Results: Exposure to MTA extracts resulted in reduced mRNA expression levels of IL‐1α and IL‐6, as well as reduced expression of phosphorylated NF‐κB, in LPS‐stimulated RAW264.7 cells. Exposure to MTA extracts induced Ca2+ influx, which was blocked by NPS2143, an antagonist of calcium‐sensing receptor (CaSR); Ca2+ influx then triggered activation of calcineurin/NFAT signalling and enhanced mRNA expression of Egr2. Enforced expression of Egr2 in RAW264.7 cells promoted the expression of both IL‐10 and Socs3. In vivo application of MTA onto rat molar pulp tissue resulted in the appearance of Egr2‐expressing cells that coexpressed CD163, a typical M2 macrophage marker. Conclusions: Mineral trioxide aggregate extracts induced downregulation of IL‐1α and IL‐6 in LPS‐stimulated RAW264.7 cells via CaSR‐induced activation of calcineurin/NFAT/Egr2 signalling and subsequent upregulation of IL‐10 and Socs3. [ABSTRACT FROM AUTHOR]

Background and purpose: The association between an increased supraventricular ectopic beat (SVEB) and subclinical cerebrovascular disease remains unclear. Given the emerging concept that an increased SVEB is a marker of atrial cardiomyopathy or atherosclerosis burden, we sought to determine whether excessive supraventricular ectopic activity (ESVEA) is associated with a higher burden of subclinical cerebrovascular disease in the middle‐aged to older cohort with neither apparent stroke nor atrial fibrillation. Methods: We conducted a cross‐sectional population‐based study of 462 men (mean age, 68.1 years) who underwent 24‐h Holter electrocardiography and brain magnetic resonance imaging. ESVEA was defined as the presence of >10 SVEBs/h. Subclinical cerebrovascular diseases were defined as silent brain infarct (SBI), white matter hyperintensity (WMH) and intracranial atherosclerotic stenosis (ICAS). The association of ESVEA with the presence of subclinical cerebrovascular diseases was adjusted for potential confounding covariates. Results: A total of 88 (19.0%) participants had ESVEA and 81 (17.5%), 91 (19.7%) and 109 (23.6%) had SBI, WMH and ICAS, respectively. In multivariable‐adjusted Poisson regression with robust error variance, ESVEA was associated with the presence of WMH (relative risk, 1.58; 95% confidence interval, 1.06–2.36) and ICAS (relative risk, 1.49; 95% confidence interval, 1.02–2.18), but not with that of SBI (relative risk, 1.32; 95% confidence interval, 0.86–2.01). These associations were consistent when the graded distributions of subclinical cerebrovascular diseases were applied as outcomes in ordinal logistic regression. Conclusions: The ESVEA was independently associated with higher burdens of WMH and ICAS. This suggests that increased SVEBs might improve risk stratification of individuals at high risk of subclinical cerebrovascular disease and consequently apparent ischaemic stroke. [ABSTRACT FROM AUTHOR]

Central nervous system lomentosporiosis is a rare pathological condition in immunocompromised patients. We describe a fatal case of meningitis caused by Lomentospora prolificans (which was previously named Scedosporium prolificans), after an allogeneic hematopoietic stem cell transplantation (allo- HSCT). To our knowledge, no cases of Lomentospora meningitis following allo- HSCT have been reported previously. Particularly in neutropenic patients, it is important to consider L. prolificans when a fungal infection is suspected and antifungal agents are ineffective. [ABSTRACT FROM AUTHOR]

Wearing dentures has been believed to decrease the instability of the postural sway using the total length of centre of pressure (CoP) trajectory or the magnitude of its variability. However, the physical aspects of the postural sway have not been taken into account while evaluating the CoP in patients who wear dentures. The CoP fluctuations are found to show a random walk process. Therefore, changes in the random movement of CoP caused by wearing dentures should be examined by nonlinear dynamics that enables analysis of the characteristics found in the random movement. We evaluated the effect of complete denture installation on CoP sway for twenty-six edentulous patients by performing the following steps. First, we excluded subjects who did not show crossover in spectral analyses. Then, we evaluated the spectral characteristics and phase shifts of the velocities of CoP sway for the subjects who showed crossover. We found that wearing complete dentures decreased the fluctuations in the high-frequency part of the power spectral density ( PSD) and the phase shift in the mediolateral direction. On the other hand, we also found that the use of complete dentures decreased the fluctuations of PSD amplitude in the anteroposterior direction. From the point of view of the kinetic energy of the musculoskeletal system, we suggested that the use of complete dentures could reduce the energy consumption for the standing posture. [ABSTRACT FROM AUTHOR]

Background and Purpose: Cerebral aneurysm is a frequent cerebrovascular event and a major cause of fatal subarachnoid haemorrhage, but there is no medical treatment for this condition. Haemodynamic stress and, recently, chronic inflammation have been proposed as major causes of cerebral aneurysm. Nevertheless, links between haemodynamic stress and chronic inflammation remain ill-defined, and to clarify such links, we evaluated the effects of prostaglandin E(2) (PGE(2) ), a mediator of inflammation, on the formation of cerebral aneurysms.Experimental Approach: Expression of COX and prostaglandin E synthase (PGES) and PGE receptors were examined in human and rodent cerebral aneurysm. The incidence, size and inflammation of cerebral aneurysms were evaluated in rats treated with COX-2 inhibitors and mice lacking each prostaglandin receptor. Effects of shear stress and PGE receptor signalling on expression of pro-inflammatory molecules were studied in primary cultures of human endothelial cells (ECs).Key Results: COX-2, microsomal PGES-1 and prostaglandin E receptor 2 (EP(2) ) were induced in ECs in the walls of cerebral aneurysms. Shear stress applied to primary ECs induced COX-2 and EP(2) . Inhibition or loss of COX-2 or EP(2) in vivo attenuated each other's expression, suppressed nuclear factor κB (NF-κB)-mediated chronic inflammation and reduced incidence of cerebral aneurysm. EP(2) stimulation in primary ECs induced NF-κB activation and expression of the chemokine (C-C motif) ligand 2, essential for cerebral aneurysm.Conclusions and Implications: These results suggest that shear stress activated PGE(2) -EP(2) pathway in ECs and amplified chronic inflammation via NF-κB. We propose EP(2) as a therapeutic target in cerebral aneurysm. [ABSTRACT FROM AUTHOR]

Nozaki K, Kaku M, Yamashita Y, Yamauchi M, Miura H. Effect of cyclic mechanical loading on osteoclast recruitment in periodontal tissue. J Periodont Res 2009; doi: 10.1111/j.1600-0765.2008.01193.x. © 2009 The Authors. Journal compilation © 2009 Blackwell Munksgaard Background and Objective: It is well accepted that cyclic mechanical loading induces osteoclastogenesis in periodontal tissue, but its molecular mechanisms are not well understood, in part because of a lack of appropriate models. In this study, we investigated a novel device that allows cyclic mechanical loading to be performed in a well-controlled manner. Furthermore, by employing this model, the effect of cyclic loading on osteoclast recruitment in the periodontal tissue was described. Material and Methods: By using a newly developed device, the cyclic loading of 20 n (reference loading corresponding to the fracture hardness of dietary pellets) and two excessive loadings (i.e. 30 and 40 n) were applied to maxillary right molars in rats for up to 7 d, and osteoclast recruitment in the periodontal tissue was evaluated by analyzing relevant marker proteins using immunohistochemistry. Results: Osteoclastogenesis was induced by day 3 within alveolar bone subjected to a compression force of 30 n. With both 30 and 40 n loadings, cells that were positive to for tartrate-resistant acid phosphate, receptor activator of nuclear factor-κB ligand and osteoprotegerin were significantly increased in the alveolar bone/periodontal ligament in a time-dependent manner. Conclusion: A new device was developed that allows various levels of cyclic mechanical loading to be exerted. By using this device in rats, early events of osteoclast recruitment in the periodontal tissues were observed with excessive loadings in a time-dependent manner, indicating the usefulness of this model. [ABSTRACT FROM AUTHOR]