Myocardial cathepsin D is downregulated in sudden cardiac death.

Cathepsins are the major lysosomal proteases that maintain intracellular homeostasis. Herein, we investigated the alterations in myocardial cathepsin expression during aging, cardiac hypertrophy, and sudden cardiac death (SCD). Cardiac tissue and blood were sampled from autopsy cases. Subjects were classified into three groups: SCD with cardiac hypertrophy (SCH), compensated cardiac hypertrophy (CCH), and control. Immunoblotting was performed for the major cardiac cathepsins and their targets: cathepsin B, D, and L (CTSB/D/L), p62, ATP synthase subunit c (ATPSC), and α-synuclein (ASNC). Immunohistochemical analysis and ELISA using serum samples were performed for CTSD. Cardiac CTSB and CTSD were upregulated with age (r = 0.63 and 0.60, respectively), whereas the levels of CTSL, p62, ATPSC, and ASNC remained unchanged. In age-matched groups, cardiac CTSD was significantly downregulated in SCH (p = 0.006) and CTSL was moderately downregulated in CCH (p = 0.021); however, p62, ATPSC, and ASNC were not upregulated in cardiac hypertrophy. Immunohistochemistry also revealed decreased myocardial CTSD levels in SCH, and serum CTSD levels were relatively lower in SCH cases. Overall, these results suggest that upregulation of cardiac CTSB and CTSD with age may compensate for the elevated proteolytic demand, and that downregulation of CTSD is potentially linked to SCH

Hochuekkito Combined with Pulmonary Rehabilitation in Apathetic Patients with Chronic Obstructive Pulmonary Disease: A Randomized Controlled Pilot Trial

The main treatment goals for chronic obstructive pulmonary disease (COPD) are the reduction of its symptoms and future risks. The addition of the traditional herbal medicine Hochuekkito (TJ-41) treatment to pulmonary rehabilitation (PR) has been reported to improve dyspnea and health-related quality of life (HRQOL) in patients with COPD. However, the reason for this improvement is not sufficiently understood. The purpose of the present study was to investigate whether the addition of TJ-41 treatment to PR improves symptoms of apathy, dyspnea, and HRQOL and increases physical activity among apathetic patients with COPD. Apathetic patients with COPD were randomly assigned to receive low-intensity exercise with (TJ-41 group) or without (control group) TJ-41 treatment for 12 weeks. A total of 29.9% of COPD patients had apathetic symptoms without severe depression. After the 12-week treatment, Apathy Scale, Patient Health Questionnaire-9, visual analog scale for dyspnea, and COPD assessment test energy scores decreased significantly in the TJ-41 group (p < 0.05), but not in the control group. Additionally, the total number of steps taken was significantly higher in the TJ-41 group than in the control group. TJ-41 combined with PR may benefit apathetic patients with COPD with respect to apathy, dyspnea, HRQOL, and physical activity, but larger randomized placebo-controlled trials are required to validate the findings because of the small sample size and lack of placebo controls in this study

Background Factors of Reflux Esophagitis and Non-Erosive Reflux Disease: A Cross-Sectional Study of 10,837 Subjects in Japan

<div><p>Background</p><p>Despite the high prevalence of gastroesophageal reflux disease (GERD), its risk factors are still a subject of controversy. This is probably due to inadequate distinction between reflux esophagitis (RE) and non-erosive reflux disease (NERD), and is also due to inadequate evaluation of adjacent stomach. Our aim is therefore to define background factors of RE and NERD independently, based on the evaluation of <i>Helicobacter pylori</i> infection and gastric atrophy.</p><p>Methods</p><p>We analyzed 10,837 healthy Japanese subjects (6,332 men and 4,505 women, aged 20–87 years) who underwent upper gastrointestinal endoscopy. RE was diagnosed as the presence of mucosal break, and NERD was diagnosed as the presence of heartburn and/or acid regurgitation in RE-free subjects. Using GERD-free subjects as control, background factors for RE and NERD were separately analyzed using logistic regression to evaluate standardized coefficients (SC), odds ratio (OR), and <i>p</i>-value.</p><p>Results</p><p>Of the 10,837 study subjects, we diagnosed 733 (6.8%) as RE and 1,722 (15.9%) as NERD. For RE, male gender (SC = 0.557, OR = 1.75), <i>HP</i> non-infection (SC = 0.552, OR = 1.74), higher pepsinogen I/II ratio (SC = 0.496, OR = 1.64), higher BMI (SC = 0.464, OR = 1.60), alcohol drinking (SC = 0.161, OR = 1.17), older age (SC = 0.148, OR = 1.16), and smoking (SC = 0.129, OR = 1.14) are positively correlated factors. For NERD, <i>HP</i> infection (SC = 0.106, OR = 1.11), female gender (SC = 0.099, OR = 1.10), younger age (SC = 0.099, OR = 1.10), higher pepsinogen I/II ratio (SC = 0.099, OR = 1.10), smoking (SC = 0.080, OR = 1.08), higher BMI (SC = 0.078, OR = 1.08), and alcohol drinking (SC = 0.076, OR = 1.08) are positively correlated factors. Prevalence of RE in subjects with chronic <i>HP</i> infection and successful <i>HP</i> eradication denotes significant difference (2.3% and 8.8%; <i>p</i><0.0001), whereas that of NERD shows no difference (18.2% and 20.8%; <i>p</i> = 0.064).</p><p>Conclusions</p><p>Significantly associated factors of NERD are considerably different from those of RE, indicating that these two disorders are pathophysiologically distinct. Eradication of <i>Helicobacter pylori</i> may have disadvantageous effects on RE but not on NERD.</p></div

Comparison between endoscopic reflux esophagitis (RE) patients and GERD-free subjects.

<p>CI, confidence interval; <i>H. pylori</i>, <i>Helicobacter pylori</i>; PG, pepsinogen; BMI, body mass index; y.o., years old. Chi-square test was used for statistical evaluation, and the correlation of each background factor between RE patients and GERD-free subjects was calculated respectively. The level of significance in the univariate analyses was set at <i>p</i> value <0.05 (*).</p

Comparison between non-erosive reflux disease (NERD) patients and GERD-free subjects.

<p>CI, confidence interval; <i>H. pylori</i>, <i>Helicobacter pylori</i>; PG, pepsinogen; BMI, body mass index; y.o., years old. Chi-square test was used for statistical evaluation; the correlation of each subject background factor between NERD patients and GERD-free subjects was calculated respectively as an odds ratio (OR) with 95% confidence interval (CI). The level of significance in the univariate analyses was set at <i>p</i> value <0.05 (*).</p

Correlation between non-erosive reflux esophagitis (NERD) and selected background factors.

<p>CI, confidence interval; <i>H. pylori</i>, <i>Helicobacter pylori</i>; PG, pepsinogen; BMI, body mass index. We evaluated age and BMI as continuous variables. Multiple logistic regression analysis was applied to calculate standardized coefficients and odds ratio for selected seven variables. The level of significance was set at <i>p</i> value <0.05 (†). The seven variables are shown in order of the absolute values of standardized coefficients.</p

Prevalence of reflux esophagitis (RE) and non-erosive reflux esophagitis (NERD) among “chronic <i>H. pylori</i> infection” subjects and “<i>H. pylori</i> successfully eradicated” subjects.

<p><i>H. pylori</i>, <i>Helicobacter pylori</i>. From the viewpoint of both RE and NERD, chi-square test was used for statistical evaluation. The level of significance in the univariate analyses was set at <i>p</i> value <0.05 (†).</p

Correlation between endoscopic reflux esophagitis (RE) and selected background factors.

<p>CI, confidence interval; <i>H. pylori</i>, <i>Helicobacter pylori</i>; PG, pepsinogen; BMI, body mass index. We evaluated age and BMI as continuous variables. Multiple logistic regression analysis was applied to calculate standardized coefficients and odds ratio for selected seven variables. The seven variables are shown in order of the absolute values of standardized coefficients. The level of significance was set at <i>p</i> value <0.05 (*).</p

Multivariate analysis of the 6,433 study subjects evaluating associations of the seven background factors with UGI-XR-based atrophic gastritis (atrophic gastritis diagnosed by double-contrast upper gastrointestinal barium X-ray radiography).

<p>Multivariate analysis of the 6,433 study subjects evaluating associations of the seven background factors with UGI-XR-based atrophic gastritis (atrophic gastritis diagnosed by double-contrast upper gastrointestinal barium X-ray radiography).</p