How to evaluate effects of occupational therapy - lessons learned from an exploratory randomized controlled trial.

BACKGROUND: Although occupational therapy (OT) is frequently prescribed in clinical practice, there is still insufficient evidence regarding its efficacy to improve Parkinson's Disease (PD)-related activity limitations. OBJECTIVES: To evaluate the efficacy of OT and the validity of different outcome-parameters to reflect efficacy, including gold-standard clinical rating scales and quantitative motor assessments. METHODS: 40 patients were included in an exploratory, randomized-controlled, single-blinded trial, receiving either (I) ten weeks of OT, with a main focus on motor aspects of activity limitations and a ten-week follow-up assessment or (II) no intervention. Inclusion criteria were diagnosis of PD and Hoehn & Yahr stage 2-3. Patients with major depression, other neurological or orthopedic diseases or OT beforehand were excluded from the study. To monitor treatment effects the MDS-UPDRS part II and III were used for patient- and clinician-based assessment. Objective Pegboard as well as Q-Motor "tremormotography" and "digitomotography" were applied. RESULTS: The interventional group reported a subjective amelioration of activity limitations, with a significant improvement of MDS-UPDRS part II at the end of the study (p = 0.030). However, clinician's rating and quantitative motor assessment failed to detect a significant improvement of motor impairment and fine motor control. CONCLUSIONS: This study goes in line with previous trials, showing an individual improvement of activity limitations from the patients' point of view. The discrepancy between self-perception, focusing on activity limitation, and clinician-based rating, focusing on motor impairment, challenges the current gold standard assessments as valid outcome parameters for occupational therapy trials aiming for an individualized improvement of disease burden.

Enzymatic degradation of the triterpenoid saponin helianthoside 2.

Helianthoside 2 (1), the main bisdesmosidic saponin of Helianthus annuus L. was converted to the products 2, 3 and 4 by several, optimized enzymatic hydrolysis methods. Monosaccharide units of the acylglycosidic at C-28 of the sapogenin bonded, linear chain oligosaccharide were cleaved, but the branched trisaccharide at C-3 of the aglycone are stable under the conditions used. Compounds 2 and 3 are new triterpenoid glycosides, which were characterized as 28-O-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranoside (2) and 28-O-alpha-L-arabinopyranoside (3) of 3-O-[alpha-L-rhamnopyranosyl-(1-->3)][beta-D-xylopyranosyl-(1-->4)] beta-D-glucopyranoside of 3 beta,16 alpha-dihydroxy-olean-12-en-28-oic acid.

Expression of the extraneuronal monoamine transporter (uptake2) in human glioma cells.

Tritiated methylphenylpyridinium ([3H]MPP+), a substrate of the neuronal and extraneuronal noradrenaline transporter (uptake1 and uptake2, respectively) and of the organic cation transporter (OCT1), was used to characterize the amine transport system of the established human glioma cell line SK-MG-1. Uptake of [3H]MPP+ (25 nM) into SK-MG-1 cells increased linearly with time for up to 15 min. Selective uptake1 inhibitors (e.g. (+)oxaprotiline) or omission of Na+ or Cl-ions did not affect [3H]MPP+ uptake, whereas uptake2 inhibitors such as O-methyl-isoprenaline (OMI) or corticosterone as well as depolarizing concentrations of K+ or Ba2+ strongly reduced [3H]MPP+ uptake. Initial rates of OMI(100 microM)-sensitive [3H]MPP+ uptake were saturable, with a K(m) of about 17 microM and a maximal rate of about 50 pmol/(min x mg protein). IC50 (or Ki) values for inhibition of [3H]MPP+ uptake by substrates and inhibitors of uptake2 or OCT1 were highly significantly correlated with published IC50 values for inhibition of uptake2 but not with corresponding values for inhibition of OCT1. The results presented here clearly demonstrate that human glioma cells express an uptake2 transporter. Thus, glial cells in the human central nervous system endowed with this transporter are likely to contribute to the inactivation of neuronally released noradrenaline.

Accelerated maximal velocity of the red blood cell Na+/K+ pump in hyperlipidemia is related to increase in 1-palmitoyl,2-arachidonoyl-plasmalogen phosphatidylethanolamine.

Among several phospholipid classes and molecular species of phosphatidylcholine and phosphatidylethanolamine (PE) analyzed, only the percentage of the molecular species 1-palmitoyl,2-arachidonoyl (16: 0/20: 4)-plasmalogen-(alkenylacyl)-PE showed positive relations to the maximal activity and to the dissociation constant of the red blood cell Na+/K+ pump for Na+ in normo- and hyperlipidemic donors. A preferential interaction of this molecular species with the Na+/K+ pump is proposed.

Molecular species of membrane phospholipids containing arachidonic acid and linoleic acid contribute to the interindividual variability of red blood cell Na(+)-Li+ countertransport: in vivo and in vitro evidence.

Previous studies indicate a particular sensitivity of red blood cell Na(+)-Li+ countertransport activity to small variations in the fatty acid composition of membrane phospholipids. To assess whether the interindividual variability of Na(+)-Li+ countertransport is related to differences in the species pattern of erythrocyte phosphatidylcholine (PC) and phosphatidylethanolamine (PE) in vivo, the molecular species composition of PC and PE as well as the kinetics of Na(+)-Li+ countertransport were analyzed in parallel in normo- and hyperlipidemic donors. Both in diacyl-PC and in diacyl-PE the species 16:0/20:4 and 16:0/18:2 were, respectively, positively and negatively related to the apparent maximal velocity of Na(+)-Li+ countertransport. The sum of all species with 20:4 at sn2 of diacyl-PE exhibited a strong positive (r = 0.82, 2p < 0.001), and those containing 18:2 a negative correlation (r = -0.63, 2p < 0.01) to the transport activity. Essentially similar connections were observed between these species and the apparent affinity of the transport system for intracellular Na+. To evaluate whether the associations between molecular species of membrane phospholipids and Na(+)-Li+ countertransport activity were indicative of a causal relationship, the species 16:0/20:4-PC and 16:0/18:2-PC were selectively introduced into the erythrocyte membrane by means of the PC-specific transfer protein. Replacement of 11% of native PC by 16:0/18:2-PC inhibited the transport rate by about 25%. Exchange of 6 and 9% of PC with 16:0/20:4-PC, in contrast, accelerated the transport rate by 30 and 60%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Relations of sodium-lithium countertransport kinetics to plasma and red cell membrane phospholipids in hyperlipidemia.

As compared to 7 normolipidemic donors, the maximal velocity of sodium-lithium countertransport was accelerated by nearly 70% in 10 patients with elevated levels of triglyceride-rich lipoproteins and tended to be stimulated also in 5 patients with hypercholesterolemia. No significant differences were observed between normolipidemia and both hyperlipidemic groups for the apparent affinities of the transport system for intracellular sodium and extracellular lithium. Strong positive relations of the maximal activity of sodium-lithium countertransport to the percentages of red cell membrane phosphatidylcholine (r = 0.85, 2P < 0.001), the phosphatidylcholine/sphingomyelin (r = 0.82, 2P < 0.001) and the phosphatidylcholine/phosphatidylethanolamine ratio (r = 0.81, 2P < 0.001) were seen in all donors. A negative correlation was found to membrane sphingomyelin (r = -0.72, 2P < 0.001). Also plasma phosphatidylcholine and sphingomyelin exhibited positive and negative associations, respectively, to the maximal activity of sodium-lithium countertransport (r = 0.66, 2P < 0.01 and r = -0.78, 2P < 0.001). Among several plasma lipoprotein parameters investigated, total triglycerides or VLDL cholesterol levels showed independent relations to both the plasma and the membrane phosphatidylcholine/sphingomyelin ratio as well as to the maximal velocity of sodium-lithium countertransport. The results indicate that an increase in red cell membrane phosphatidylcholine and a concomitant fall in sphingomyelin are closely associated with the acceleration of sodium-lithium countertransport in hyperlipidemia.

Changes of membrane phospholipid composition of human erythrocytes in hyperlipidemias. I. Increased phosphatidylcholine and reduced sphingomyelin in patients with elevated levels of triacylglycerol-rich lipoproteins.

The composition of red blood cell membrane and plasma phospholipids has been analyzed in patients with hyperlipidemias. In red cells of patients with elevated levels of triacylglycerol-rich lipoproteins, phosphatidylcholine (PC) was raised and sphingomyelin (SM) reduced, resulting in a 20% increase of the membrane PC/SM ratio. In plasma phospholipids of these patients PC and SM levels were also higher and lower, respectively and the plasma PC/SM ratio was elevated by more than 50%. Close positive correlations between plasma and membrane phospholipids were obtained for PC, SM and the PC/SM ratio in normolipidemic and hyperlipidemic donors. Plasmalogen phosphatidylethanolamine (PE), a supposed endogenous protector against lipid oxidation, was reduced by about 20% in red cell membrane lipids in hyperlipidemic patients. Also plasmalogen-PE in plasma tended to be reduced in hyperlipidemic donors. Plasma HDL levels were positively related to the content of plasmalogen PE in the red cell membrane. In conclusion, there are closely related increases in PC/SM ratios in plasma and the red cell membrane in patients with elevated levels of triacylglycerol-rich lipoproteins. It is speculated that decreases in red cell membrane plasmalogen-PE in hyperlipidemic patients could be related to impaired antioxidant protection, possibly as a consequence of reductions in plasma HDL levels.