Quantitative Estimation of the Hydrogen-Atom-Donating Ability of 4-Substituted Hantzsch Ester Radical Cations.

The purpose of this study is to investigate thermodynamic and kinetic properties on the hydrogen-atom-donating ability of 4-substituted Hantzsch ester radical cations (XRH•+), which are excellent NADH coenzyme models. Gibbs free energy changes and activation free energies of 17 XRH•+ releasing H• [denoted as ΔG HD o(XRH•+) and ΔG HD ≠(XRH•+)] were calculated using density functional theory (DFT) and compared with that of Hantzsch ester (HEH2) and NADH. ΔG HD o(XRH•+) range from 19.35 to 31.25 kcal/mol, significantly lower than that of common antioxidants (such as ascorbic acid, BHT, the NADH coenzyme, and so forth). ΔG HD ≠(XRH•+) range from 29.81 to 39.00 kcal/mol, indicating that XRH•+ spontaneously releasing H• are extremely slow unless catalysts or active intermediate radicals exist. According to the computed data, it can be inferred that the Gibbs free energies and activation free energies of the core 1,4-dihydropyridine radical cation structure (DPH•+) releasing H• [ΔG HD o(DPH•+) and ΔG HD ≠(DPH•+)] should be 19-32 kcal/mol and 29-39 kcal/mol in acetonitrile, respectively. The correlations between the thermodynamic driving force [ΔG HD o(XRH•+)] and the activation free energy [ΔG HD ≠(XRH•+)] are also explored. Gibbs free energy is the important and decisive parameter, and ΔG HD ≠(XRH•+) increases in company with the increase of ΔG HD o(XRH•+), but no simple linear correlations are found. Even though all XRH•+ are judged as excellent antioxidants from the thermodynamic view, the computed data indicate that whether XRH•+ is an excellent antioxidant in reaction is decided by the R substituents in 4-position. XRH•+ with nonaromatic substituents tend to release R• instead of H• to quench radicals. XRH•+ with aromatic substituents tend to release H• and be used as antioxidants, but not all aromatic substituted Hantzsch esters are excellent antioxidants.

Comparison of the clinical characteristics and comprehensive assessments of the 2011 and 2017 GOLD classifications for patients with COPD in China.

OBJECTIVE: Compared with the 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD), there have been significant changes in the 2017 GOLD classification. The purpose of this study was to analyze the changes in clinical characteristics of the new A-B-C-D system and to explore its role in comprehensive assessment of COPD. SUBJECTS AND METHODS: A total of 631 stable COPD patients were included in a cross-sectional survey. Data collected included baseline data and pulmonary function testing results, respiratory muscle strength, symptoms and quality of life, exercise capacity, nutritional status, and anxiety and depression as a comprehensive assessment. Based on the 2011 GOLD and 2017 GOLD classifications, patients were divided into Groups A1-D1 and Groups A2-D2, respectively. RESULTS: In the 2011 GOLD, 64 subjects in Group C1 were reclassified into Group A2 (41.6%), while 77 subjects in Group D1 were reclassified into Group B2 (27.1%). The old and new grading systems were somewhat consistent (Cohen's kappa=0.6963, P<0.001). Lung function was lower, while the body mass index, airflow obstruction, dyspnea, and exercise capacity index (BODE index) was higher in Group A2 than in Group A1 (P<0.001). In Group B2, lung function, 6-minute walking distance (6MWD), and respiratory muscle strength were significantly lower than in Group B1 (P<0.001), while the BODE index (P<0.001) was higher. In comprehensive assessment, subjects in Groups B2 and D2 had significantly lower lung function, 6MWD, respiratory muscle strength, quality of life, higher symptom scores, and BODE index than subjects in Group A2 (P<0.001). The differences between Group A2 and C2 were small. CONCLUSION: Compared with the 2011 GOLD, the 2017 GOLD reclassified more patients into Groups A and B, those with significantly worse lung function and higher BODE index. In the comprehensive assessment of the new classification, Groups B and D may have greater disease severity. However, the effectiveness of the new grading system in predicting patient prognosis, and its guidance on the use of drugs, remains to be explored in future studies.

Cycle ergometer and inspiratory muscle training offer modest benefit compared with cycle ergometer alone: a comprehensive assessment in stable COPD patients.

BACKGROUND: Cycle ergometer training (CET) has been shown to improve exercise performance of the quadriceps muscles in patients with COPD, and inspiratory muscle training (IMT) may improve the pressure-generating capacity of the inspiratory muscles. However, the effects of combined CET and IMT remain unclear and there is a lack of comprehensive assessment. MATERIALS AND METHODS: Eighty-one patients with COPD were randomly allocated to three groups: 28 received 8 weeks of CET + IMT (combined training group), 27 received 8 weeks of CET alone (CET group), and 26 only received 8 weeks of free walking (control group). Comprehensive assessment including respiratory muscle strength, exercise capacity, pulmonary function, dyspnea, quality of life, emotional status, nutritional status, and body mass index, airflow obstruction, and exercise capacity index were measured before and after the pulmonary rehabilitation program. RESULTS: Respiratory muscle strength, exercise capacity, inspiratory capacity, dyspnea, quality of life, depression and anxiety, and nutritional status were all improved in the combined training and CET groups when compared with that in the control group (P<0.05) after pulmonary rehabilitation program. Inspiratory muscle strength increased significantly in the combined training group when compared with that in the CET group (ΔPImax [maximal inspiratory pressure] 5.20±0.89 cmH2O vs 1.32±0.91 cmH2O; P<0.05). However, there were no significant differences in the other indices between the two groups (P>0.05). Patients with weakened respiratory muscles in the combined training group derived no greater benefit than those without respiratory muscle weakness (P>0.05). There were no significant differences in these indices between the patients with malnutrition and normal nutrition after pulmonary rehabilitation program (P>0.05). CONCLUSION: Combined training is more effective than CET alone for increasing inspiratory muscle strength. IMT may not be useful when combined with CET in patients with weakened inspiratory muscles. Nutritional status had slight impact on the effects of pulmonary rehabilitation. A comprehensive assessment approach can be more objective to evaluate the effects of combined CET and IMT.