Non-motor symptoms in Parkinson’s disease

Parkinson’s disease is a hypokinetic movement disorder with cardinal motor features of bradykinesia, resting tremor and rigidity. However, non-motor symptoms, such as cognitive, neuropsychiatric, sleep, autonomic and sensory disturbances are gaining increasing attention. These non-motor symptoms may be intrinsic to the disease pathology or may be results of treatment with dopaminergic agents. Given that most, if not all, patients with Parkinson’s disease will experience non-motor symptoms, it is important to be sensitive to these phenomena, especially since some non-motor signs may precede motor impairment. Treatment may include interventions independent of traditional, dopaminergic anti-Parkinson therapy or may be tailored to increase or reduce dopamine responsiveness of the symptom.

     

Protective effect of beta-glucan extracted from Saccharomyces cerevisiae, against DNA damage and cytotoxicity in wild-type (k1) and repair-deficient (xrs5) CHO cells.

A large number of functional foods, including those that contain beta-glucan, have been shown to prevent the development of cancer and other chronic diseases. The aim of the present study was to elucidate its mechanism of action, as well as to understand its effects as an antigenotoxic, anticlastogenic agent, and to determine its capacity to preserve cell viability. The investigation was carried out in the CHO-k1 and CHO-xrs5 cell lines. The cytokinesis-blocked micronucleus assay indicated that the different doses of beta-glucan examined (5, 10, 20 and 40 microg/ml) did not show clastogenic effects. In the CHO-k1 cell line, a chemopreventive effect could be observed in all the protocols tested: pre-treatment (% reduction of 35.0-57.3), simultaneous treatment (simple--5 reduction of 19.7-55.6 and with pre-incubation--of 42.7-56.4) and post-treatment (% reduction of 17.9-37.6). This finding indicates mechanisms of action involving desmutagenesis and bioantimutagenesis, albeit the latter having a lesser role. However, in the repair-deficient CHO-xrs5 cells, beta-glucan did not show a protective effect with post-treatment (% reduction of 2.96), thus supporting the involvement of bioantimutagenesis. The comet assay in CHO-k1 cells demonstrated that beta-glucan has neither a genotoxic nor an antigenotoxic effect. Cell viability tests indicated that beta-glucan preserves cell viability in both cell lines, preventing apoptotic events. These findings suggest that beta-glucan, when present in foods, could provide them with nutraceutical characteristics and act as a dietary supplement, or that beta-glucan could be used in new drug development.     

Physical activity attitudes, preferences, and practices in African American, Hispanic, and Caucasian girls.

Physical activity levels in girls decline dramatically during adolescence, most profoundly among minorities. To explore ethnic and racial variation in attitudes toward physical activity, semistructured interviews (n = 80) and physical activity checklists (n = 130) are conducted with African American, Hispanic, and Caucasian middle school girls in six locations across the United States. Girls from all groups have similar perceptions of the benefits of physical activity, with staying in shape as the most important. Girls have similar negative perceptions of physical activity, including getting hurt, sweating, aggressive players, and embarrassment. Chores, running or jogging, exercises, and dance are common activities for girls regardless of ethnicity. Basketball, swimming, running, and dance are commonly cited favorite activities, although there are slight differences between ethnic groups. The results suggest that factors other than ethnicity contribute to girls' physical activity preferences and that distinct interventions may not be needed for each ethnic group.     

Role of tryptophan in the elevated serotonin-turnover in hepatic encephalopathy

Summary. The increase of the brain levels of 5-hydroxyindoleacetic acid (5-HIAA) in hepatic encephalopathy (HE) suggests an increased turnover of serotonin (5-HT). To study the role of tryptophan on the increased brain 5-HT metabolism in HE, we attempted to monitor brain levels of tryptophan in rats with thioacetamide-induced acute liver failure by intravenous infu-sion of branched-chain amino acids (BCAA). The effect of this treatment on 5-HT synthesis and metabolism was investigated in five brain areas. BCAA-infusions (1 and 2 gm/kg/24 h) increased the ratio BCAA/aromatic amino acids in plasma two- and fourfold, respectively, and lowered both plasma and brain levels of tryptophan. At the higher BCAA-dose all parameters suggesting an altered brain 5-HT metabolism (increased brain levels of 5-HT and 5-HIAA, increased 5-HIAA/5-HT ratio) were almost completely normalized. These results provide further evidence for the role of tryptophan in the elevation of brain 5-HT metabolism and for a potential role of BCAA in the treatment of HE. Received December 17, 1997; accepted March 19, 1998     

Some facts about sleep relevant for Landau-Kleffner syndrome

Our understanding of the neural mechanisms of non–rapid eye movement sleep (NREM) is steadily increasing. Given the intriguing activation of paroxysmal activity during NREM sleep in patients with Landau-Kleffner syndrome (LKS), a thorough characterization of commonalities and differences between the neural correlates of LKS paroxysms and normal sleep oscillations might provide useful information on the neural underpinning of this disorder. Especially, given the suspected role of sleep in brain plasticity, this type of information is needed to assess the link between cognitive deterioration and electroencephalography (EEG) paroxysms during sleep.     

A Norwegian 15D value algorithm: proposing a new procedure to estimate 15D value algorithms

Purpose

So far there is no Norwegian value algorithm to inform healthcare decision making. The 15D health state values estimated with the original 15D valuation procedure tend to be higher than the values of other generic preference-based health-related quality of life (HRQoL) instruments. The main purpose of this study was to use a new 15D valuation procedure to estimate Norwegian 15D health state values and to explore their empirical performance.

Methods

The visual analogue scale was used to collect 15D valuation data in a representative sample of the Norwegian general population. The new procedure used fewer valuation tasks and anchored the 15D health state values in an empirically assessed range. The Norwegian 15D health state values were compared to the values of five HRQoL instruments which were provided by Norwegian residents belonging to seven disease groups and a healthy population.

Results

The Norwegian 15D health state values ranged from 1 to ??0.52. Compared to 15D health state values estimated with the original procedure, the Norwegian 15D health state values were lower and more in line with values of other HRQoL instruments.

Conclusions

The new 15D valuation procedure is simpler, links the 15D health state values better to the requirements of the QALY model, and provides an empirically-based range. We recommend using the new valuation procedure in future 15D valuation studies, and the Norwegian health state values for use in 15D-based health economic analyses in Norway.

     

Influence of CYP2C9 genotypes on the pharmacokinetics and pharmacodynamics of piroxicam

OBJECTIVE: Our objective was to evaluate the influence of cytochrome P450 (CYP) 2C9 polymorphisms on the pharmacokinetics and pharmacodynamics of the nonsteroidal anti-inflammatory drug piroxicam. METHODS: Thirty-five healthy subjects with CYP2C9 genotypes *1/*1 (n=17), *1/*2 (n=9), and *1/*3 (n=9) received a single oral dose of piroxicam (20 mg). Blood samples were collected at various time points up to 240 hours for measurements of the concentrations of piroxicam and thromboxane B2 (TXB2). RESULTS: Piroxicam's area under the plasma concentration-time curve from time 0 to infinity and oral clearance corrected for body weight were 154+/-37 microg.mL-1.h and 2.0+/-0.5 mL.h-1.kg-1, respectively, in CYP2C9*1/*1 individuals, as compared with 256+/-97 mL.h-1 (P=.002) and 1.3+/- 0.4 mL.h-1.kg-1 (P=.002), respectively, in CYP2C9*1/*2 individuals and 259+/- 95 mL.h-1 (P=.002) and 1.3+/- 0.4 mL.h-1.kg-1 (P=.002), respectively, in CYP2C9*1/*3 individuals. There were no significant differences between CYP2C9*1/*2 and CYP2C 9*1/*3 individuals in these pharmacokinetic parameters (P=.95 for area under the plasma concentration-time curve from time 0 to infinity and P=.94 for oral clearance corrected for body weight). The formation of TXB2, reflecting cyclooxygenase type 1 activity, showed significant differences in the area above the effect-time curves (expressed as percent of baseline TXB2.h) between CYP2C9*1/*1 (10,190 +/- 2632) and either CYP2C9*1/*2 (19,255+/-1,291 [P=.00003]) or CYP2C9*1/*3 (18,241+/- 2397 [P=.00003]). The minimum serum TXB2 concentration, however, did not differ among the different genotypes (P=.32, ANOVA). CONCLUSION: Piroxicam's oral clearance was impaired and its inhibitory effect on cyclooxygenase 1 activity was increased in CYP2C9*1/*2 or CYP2C9*1/*3 individuals, as compared with CYP2C 9*1 homozygous individuals.