Taro Kojima

Statins Protect Human Aortic Smooth Muscle Cells From Inorganic Phosphate-Induced Calcification by Restoring Gas6-Axl Survival Pathway

Vascular calcification is clinically important in the development of cardiovascular disease. It is reported that hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (statins) inhibited vascular calcification in several clinical trials. However, the mechanism is poorly understood. Recently, it has been suggested that apoptosis is one of the important processes regulating vascular smooth muscle cell (VSMC) calcification. In this study, we investigated the effect of statins on VSMC calcification by testing their effect on apoptosis, focusing in particular on regulation of the survival pathway mediated by growth arrest-specific gene 6 (Gas6), a member of the vitamin K–dependent protein family, and its receptor, Axl. In human aortic smooth muscle cells (HASMC), statins significantly inhibited inorganic phosphate (Pi)-induced calcification in a concentration-dependent manner (reduced by 49% at 0.1 &mgr;mol/L atorvastatin). The inhibitory effect of statins was mediated by preventing apoptosis, which was increased by Pi in a concentration-dependent manner, and not by inhibiting sodium-dependent phosphate cotransporter (NPC) activity, another mechanism regulating HASMC calcification. Furthermore, the antiapoptotic effect of statins was dependent on restoration of Gas6, whose expression was downregulated by Pi. Restoration of Gas6 mRNA by statins was mediated by mRNA stabilization, and not by an increase in transcriptional activity. Suppression of Gas6 using small interfering RNA and the Axl-extracellular domain abolished the preventive effect of statins on Pi-induced apoptosis and calcification. These data demonstrate that statins protected HASMC from Pi-induced calcification by inhibiting apoptosis via restoration of the Gas6-Axl pathway.

Amelioration of Vascular Endothelial Dysfunction in Obstructive Sleep Apnea Syndrome by Nasal Continuous Positive Airway Pressure

BACKGROUND Asymmetric NG,NG-dimethylarginine (ADMA) is an endogenous inhibitor of endothelial nitric oxide (NO) synthase and its plasma concentration is elevated in patients with cardiovascular risk factors, including hyperlipidemia, hypertension, diabetes, and hyperhomocysteinemia. Obstructive sleep apnea syndrome (OSAS) has been attracting attention as a risk factor for cardiovascular disorders because it often accompanies hypertension, obesity, glucose impairment, and dyslipidemia, all of which are factors in metabolic syndrome and risk factors for cardiovascular disease. METHODS AND RESULTS In the present study, flow-mediated vasodilatation (FMD) of the brachial artery and plasma concentrations of ADMA were measured before and after nasal continuous positive airway pressure (nCPAP) therapy, which abrogates apnea, in 10 male patients aged 36-69 years old, who were given a diagnosis of OSAS by polysomnography. The percent FMD (%FMD) improved significantly from 3.3+/-0.3% to 5.8+/-0.4% (p<0.01) and 6.6+/-0.3% (p<0.01), before, 1 week, and 4 weeks after nCPAP, respectively. At the same time, the plasma NOx concentrations, metabolites of NO, tended to increase, but the plasma ADMA concentration decreased inversely to %FMD and NOx. A negative correlation between %FMD and plasma ADMA concentration, and a positive correlation between %FMD and plasma NOx concentrations were observed. CONCLUSION Nasal CPAP improves endothelial function, in part by the decreasing ADMA concentration, thereby potentiating NO production.

Polypharmacy as a risk for fall occurrence in geriatric outpatients

Objective:  To investigate the predictors of falls, such as comorbidity and medication, in geriatric outpatients in a longitudinal observational study.

Association of polypharmacy with fall risk among geriatric outpatients

Aim:  To investigate the association of fall risk with comorbidities and medications in geriatric outpatients in a cross‐sectional design.

High risk of adverse drug reactions in elderly patients taking six or more drugs: Analysis of inpatient database

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Screening Tool for Older Persons’ Appropriate Prescriptions in Japanese: Report of the Japan Geriatrics Society Working Group on “Guidelines for medical treatment and its safety in the elderly”

In 2005, the Japan Geriatrics Society published a list of potentially inappropriate medication that was an extract from the “Guidelines for medical treatment and its safety in the elderly 2005.” The 2005 guidelines are due for a revision, and a new comprehensive list of potentially inappropriate medications is required.

Visceral fat accumulation and metabolic risk factor clustering in older adults.

OBJECTIVES: To examine the relationship between visceral fat area (VFA) evaluated using computed tomography (CT) scans and the number of metabolic risk factors in older adults.

Factors Associated with Prolonged Hospital Stay in a Geriatric Ward of a University Hospital in Japan

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The association of change in medication regimen and use of inappropriate medication based on beers criteria with adverse outcomes in Japanese long-term care facilities.

To describe medication use including potentially inappropriate medication (PIM) and examine the association between adverse outcomes and patient factors including PIM use in Japanese elderly patients in long‐term care facilities.

TAKO-TSUBO LEFT VENTRICULAR DYSFUNCTION CAUSED BY A FALL

older than for those younger than 60; the sensitivity and specificity were 75.0% and 68.5% in the former and 47.9% and 56.0% in the latter. From ROC curve analysis, 14 mm was chosen as the cutoff value of EV for those aged 60 and older, and 16 mm was chosen as the cutoff value of EV for those younger than 60. The sensitivity and specificity of EV in diagnosing Graves’ disease were not good in the total 113 untreated patients with Graves’ disease studied, but the sensitivity and specificity of EV for the diagnosis of Graves’ disease was good for those aged 60 and older. No association was noted between EV and TRAb.