We nonetheless take the opportunity to remark on this point that there is no high-level evidence of which vitamin D metabolites are safer and faster in normalizing sHPTH, and more importantly, the optimal dose of vitamin D3 capable of normalizing rapidly sHPTH is still being discussed and has not been established. In addition, a number of studies have demonstrated that the commonly used doses of vitamin D ( 800 UI daily), also suggested by the drug industry, may fail to normalize PTH levels in older adults with sHPTH. 8,9 The choice of calcitriol in the experimental design of our study was based mainly on the need to use a treatment that could rapidly resolve sHPTH and on the lack of available preparation of vitamin D3 at high concentrations in Italy at the time of the study.In conclusion, although we agree with the statement that plain vitamin D is the treatment of choice for vitamin D deficiency, we disagree with the interpretation of the manuscript given by Dr. Vieth, because the goal of identifying a treatment of choice for sHPTH was outside the scope of our study, whose most relevant outcome consists instead of the observation that persistence of sHPTH reduces BMD response to alendronate. To respond to the issue raised by Dr. Vieth, RCTs are needed to assess the vitamin D metabolite of choice in normalizing PTH.

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Obstructive sleep apnea syndrome (OSAS) may be one of the most important risk factors of cardiovascular disorders, although the exact mechanism remains to be elucidated. In the present study, we hypothesized that OSAS-induced hypoxic stress might be involved in the etiology of cardiovascular disorders by activating adhesion molecules, including intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and L-selectin. To examine this hypothesis, we measured circulating ICAM-1, VCAM-1, and L-selectin levels before and after sleep in OSAS patients and age-matched controls. The circulating ICAM-1, VCAM-1, and L-selectin levels increased in the OSAS patients before sleep compared with the normal subjects (ICAM-1: 392.9 +/- 48.5 vs. 201.2 +/- 55.0 ng/ml, P < 0.05; VCAM-1: 811.0 +/- 87.8 vs. 574.2 +/- 42.7 ng/ml, P < 0.05; L-selectin: 1,386.6 +/- 77.9 vs. 1,038.8 +/- 78.6 ng/ml, P < 0.01, respectively). After sleep, significantly greater levels of ICAM-1 and L-selectin, but not VCAM-1, were observed in the OSAS group. These observations suggest that OSAS-induced hypoxia activates adhesion molecules, resulting in the important risk factor of cardiovascular disorders. Treatment of OSAS can be, therefore, a potential approach to prevention of cardiovascular events.

BackgroundsAspiration pneumonia is a dominant form of community-acquired and healthcare-associated pneumonia, and a leading cause of death among ageing populations. However, the risk factors for developing aspiration pneumonia in older adults have not been fully evaluated. The purpose of the present study was to determine the risk factors for aspiration pneumonia among the elderly.Methodology and Principal FindingsWe conducted an observational study using data from a nationwide survey of geriatric medical and nursing center in Japan. The study subjects included 9930 patients (median age: 86 years, women: 76%) who were divided into two groups: those who had experienced an episode of aspiration pneumonia in the previous 3 months and those who had not. Data on demographics, clinical status, activities of daily living (ADL), and major illnesses were compared between subjects with and without aspiration pneumonia. Two hundred and fifty-nine subjects (2.6% of the total sample) were in the aspiration pneumonia group. In the univariate analysis, older age was not found to be a risk factor for aspiration pneumonia, but the following were: sputum suctioning (odds ratio [OR] = 17.25, 95% confidence interval [CI]: 13.16–22.62, p < 0.001), daily oxygen therapy (OR = 8.29, 95% CI: 4.39–15.65), feeding support dependency (OR = 8.10, 95% CI: 6.27–10.48, p < 0.001), and urinary catheterization (OR = 4.08, 95% CI: 2.81–5.91, p < 0.001). In the multiple logistic regression analysis, the risk factors associated with aspiration pneumonia after propensity-adjustment (258 subjects each) were sputum suctioning (OR = 3.276, 95% CI: 1.910–5.619), deterioration of swallowing function in the past 3 months (OR = 3.584, 95% CI: 1.948–6.952), dehydration (OR = 8.019, 95% CI: 2.720–23.643), and dementia (OR = 1.618, 95% CI: 1.031–2.539).ConclusionThe risk factors for aspiration pneumonia were sputum suctioning, deterioration of swallowing function, dehydration, and dementia. These results could help improve clinical management for preventing repetitive aspiration pneumonia.

Background-Enzymes that contribute to the local detoxification in alveoli and bronchioles have an important role in the defence mechanism against tobacco smoke. It has been suggested that genetic susceptibility to smoking injury may confer a risk for the development of chronic obstructive pulmonary disease (COPD). The polymorphisms in glutathione S-transferase P1 (GSTP1), a xenobiotic metabolising enzyme, were investigated in patients with COPD. Methods-Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were performed to genotype GSTP1 polymorphisms in exon 5 (Ile105Val) and exon 6 (Ala114Val). Blood samples were taken from 53 patients with COPD and 50 control subjects at the Tokyo University Hospital, the Juntendo University Hospital, and the Tokyo Kenbikyoin Clinic for use in the study. Results-The proportion of GSTP1/Ile105 homozygotes was significantly higher in the patients with COPD than in the control subjects (79% vs 52%). The odds ratio for GSTP1/Ile105 homozygotes versus all other genotypes was 3.5 (95% CI 2.7 to 4.6) for COPD. Polymorphism at residue 114 of GSTP1 was not found in either group.

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Cigarette smoking is thought to be a major risk factor in various lung diseases including lung cancer and emphysema. However, the direct effect of cigarette smoke on the viability of lung-derived cells has not been fully elucidated. In this study, we investigated the viability of human lung fibroblast-derived (HFL1) cells to different concentrations of cigarette smoke extract (CSE). CSE induced apoptosis at lower concentrations (10-25%) and necrosis at higher concentrations (50-100%). We also examined the effects of glutathione S-transferase P1 (GSTP1), one of the xenobiotic metabolizing and antioxidant enzymes in the lung, against the cytotoxicity of CSE. Our results indicated that the level of HFL1 cell death was decreased by transfection with a GSTP1 expression vector and was increased by GSTP1 antisense vector transfection. Therefore, transient overexpression and underexpression of GSTP1 appeared to inhibit and enhance the cytotoxic effects of CSE on HFL1 cells, suggesting that GSTP1 may have protective effects against cigarette smoke in the airway cells.