Feasibility and informativeness of the Canadian occupational performance measure for identifying priorities in patients with Parkinson's disease.

OBJECTIVE: The aim of this study was to examine the feasibility and informativeness of the Canadian Occupational Performance Measure (COPM) for identifying the priorities of patients with Parkinson's disease (PD). METHODS: The COPM was administered in patients with PD who were admitted to the hospital. Feasibility was investigated by confirming the acceptability and practicality of the COPM interview. To investigate informativeness, identified priorities were classified according to the International Classification of Functioning, Disability and Health (ICF) and were cross-referenced with data from similar studies using the Patient-Specific Functional Scale (PSFS) and the Patient-Specific Index for PD (PSI-PD). RESULTS: All 61 patients who participated in this study completed the COPM, and a total of 197 priorities were identified. The most frequently identified priorities were "Recreation and leisure," "Preparing meals," "Walking," "Doing housework," and "Caring for household objects." The priorities identified using the PSFS and the PSI-PD were less diverse and focused on "Mobility" or "Self-care." CONCLUSIONS: The COPM is a feasible and informative tool for identifying priorities in patients with PD. Its informativeness was demonstrated by its ability to identify diverse priorities across the ICF domains of "Activity and participation" that had not been identified in the studies using the PSFS and PSI-PD.

Epimagnolin A, a tetrahydrofurofuranoid lignan from Magnolia fargesii, reverses ABCB1-mediated drug resistance.

BACKGROUND: Epimagnolin A is an ingredient of the Chinese crude drug Shin-i, derived from the dried flower buds of Magnolia fargesii and Magnolia flos, which has been traditionally used for the treatment of allergic rhinitis and nasal congestion, empyema, and sinusitis. The pharmacokinetic activity of epimagnolin A remains to be evaluated. PURPOSE: In this study, we examined the possible interactions of epimagnolin A with human ATP-binding cassette (ABC) transporter ABCB1, a membrane protein vital in regulating the pharmacokinetics of drugs and xenobiotics. STUDY DESIGN/METHODS: The interaction of epimagnolin A with ABCB1 was evaluated in calcein, ATPase, and MTT assays by using Flp-In-293/ABCB1 cells and purified ABCB1 and simulated in molecular docking studies. RESULTS: Epimagnolin A inhibited calcein export by Flp-In-293/ABCB1 cells in a concentration-dependent manner in a calcein assay. ATPase assay revealed a concentration-dependent stimulation of the ATPase activity of ABCB1 by epimagnolin A. Epimagnolin A also showed saturation kinetics in the relationship between the compound-stimulated ATPase activity and the compound concentration, suggesting Michaelis-Menten kinetics similar to those of the control drug, verapamil. Km and Vmax values were calculated from Hanes-Woolf plots of (compound concentration) × (compound-stimulated ATPase activity)-1 vs. (compound concentration); the Km of epimagnolin and verapamil was 42.9 ±â€¯7.53  µM and 12.3 ±â€¯4.79  µM, respectively, and the corresponding Vmax values were 156 ±â€¯15.0  µM and 109 ±â€¯3.18  µM. Molecular docking studies on human ABCB1 showed that epimagnolin A docked to the same binding pocket as verapamil, and 3-(4,5-dimethyl-2-thiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays showed that the sensitivities of Flp-In-293/ABCB1 cells against anti-cancer drugs were enhanced upon exposure to 10  µM epimagnolin A. CONCLUSION: These results strongly suggest that epimagnolin A affects the transport activity of ABCB1 as a substrate.

Comparison of Geriatric Nutritional Risk Index scores on physical performance among elderly patients with chronic obstructive pulmonary disease.

OBJECTIVES: The Geriatric Nutritional Risk Index (GNRI) is a new prognostic indicator for nutritional status-related complications and mortality among the elderly. Here we aimed to compare 6-min walk distance (6MWD) between high and low GNRI groups for patients with COPD. METHODS: We enrolled 63 elderly men with COPD. These subjects were divided into two groups based on their GNRI scores: high GNRI group (≥92 points; n = 44) and low GNRI group (n = 19); we compared 6MWD between these groups. RESULTS: The subjects' characteristics between the high and the low GNRI groups were similar, except for BMI and serum albumin levels. 6MWD were significantly lower in the low GNRI group (279.5 ± 112.3 m versus 211.1 ± 125.3 m; p = 0.03). CONCLUSIONS: The GNRI has a more close relation with exercise tolerance and may be a useful nutritional assessment scale for elderly patients with COPD.

Nitensidine A, a guanidine alkaloid from Pterogyne nitens, is a novel substrate for human ABC transporter ABCB1.

The Pterogyne nitens (Fabaceae) tree, native to South America, has been found to produce guanidine alkaloids as well as bioactive flavonols such as kaempferol, quercetin, and rutin. In the present study, we examined the possibility of interaction between human ATP-binding cassette (ABC) transporter ABCB1 and four guanidine alkaloids isolated from P. nitens (i.e., galegine, nitensidine A, pterogynidine, and pterogynine) using human T cell lymphoblast-like leukemia cell line CCRF-CEM and its multi-drug resistant (MDR) counterpart CEM/ADR5000. In XTT assays, CEM/ADR5000 cells were resistant to the four guanidine alkaloids compared to CCRF-CEM cells, although the four guanidine alkaloids exhibited some level of cytotoxicity against both CCRF-CEM and CEM/ADR5000 cells. In ATPase assays, three of the four guanidine alkaloids were found to stimulate the ATPase activity of ABCB1. Notably, nitensidine A was clearly found to stimulate the ATPase activity of ABCB1 as strongly as the control drug, verapamil. Furthermore, the cytotoxic effect of nitensidine A on CEM/ADR5000 cells was synergistically enhanced by verapamil. Nitensidine A inhibited the extrusion of calcein by ABCB1. In the present study, the possibility of interaction between ABCB1 and two synthetic nitensidine A analogs (nitensidine AT and AU) were examined to gain insight into the mechanism by which nitensidine A stimulates the ATPase activity of ABCB1. The ABCB1-dependent ATPase activity stimulated by nitensidine A was greatly reduced by substituting sulfur (S) or oxygen (O) for the imino nitrogen atom (N) in nitensidine A. Molecular docking studies on human ABCB1 showed that, guanidine alkaloids from P. nitens dock to the same binding pocket as verapamil. Nitensidine A and its analogs exhibit similar binding energies to verapamil. Taken together, this research clearly indicates that nitensidine A is a novel substrate for ABCB1. The present results also suggest that the number, binding site, and polymerization degree of the isoprenyl moiety in the guanidine alkaloids and the imino nitrogen atom cooperatively contribute to their stimulation of ABCB1's ATPase activity.