Background
The pathophysiology of both Parkinson’s disease (PD) and progressive supranuclear palsy is characterized by a pro-oxidant state. Uric acid is an oxidative stress marker. High uric acid blood levels have been associated with a reduced risk of PD and a decreased rate of disease progression. We investigated whether a low serum concentration of uric acid is also associated with progressive supranuclear palsy.
Methods
We measured serum uric acid concentrations in a subsample of the ENGENE progressive supranuclear palsy Cohort that included 75 cases and 75 frequency-matched-by-sex healthy controls (69 spouses, 6 in-laws) from 4 centers willing to participate (Case Western, Rush University, University of Utah, and University of Louisville). Case severity was characterized using the total progressive supranuclear palsy-Rating Scale, Unified PD Rating Scale and Mattis Dementia Rating Scale. Unconditional logistic regression, Pearson’s chi-squared test and Analysis of Variance were used as appropriate.
Results
The mean uric acid level among cases (4.0 mg/dl) was not significantly lower than that of controls (4.1 mg/dl). When controlling for sex, there were no between-group statistical differences in uric acid levels. Uric acid levels were not correlated with disease severity.
Conclusion
The results of this study do not provide evidence of uric acid having a protective role in progressive supranuclear palsy, even if oxidative injury is important in the pathophysiology of this disorder. The lack of statistical significance suggests that there is no direct association between uric acid levels and progressive supranuclear palsy. However, a small inverse association cannot be excluded.
Rifampin, (Rifadin) a new antimicrobial agent introduced for the treatment of tuberculosis and other infections, is a semisynthetic antibiotic of orange-red color with mdecular weight of 822.97. I t has a macrolide-like ring structure and is the 3-(4-methyl piperazinyl iminomethyl) derivative of RifamycinIn the course of chronic toxicity studies conducted in this laboratory it was noted that the oral administration of rifampin to the M . fasicularis monkey resulted in marked reductions of the serum cholesterol levels. These results are presented below.Materials and Methods. A total of 48 cynomolgus (Macaca fasicularis ) monkeys, males 3.21 +-0.65 kg and females 2.62 t_ 0.5 kg, were used. The monkeys were caged individually in an air-conditioned environment for approximately 90 days during which time they were stabilized to diet,l feed schedule, body weight, handling and dosing procedures; and a minimum of 3 blood samples were collected to establish base line hematologic and clinical chemistry values. The monkeys were grouped and divided equally by sex for administration of single daily oral doses of 40, 80, and 110-120 mg/kg of rifampin which was suspended daily in lo./: aqueous gum acacia at a concentration of 80 mg/ml. Acacia vehicle and isoniazid (25 mg/kg/day ) for tuberculosis prophylaxis were administered to controls. I n addition, control and treated monkeys were given Tang2 (5.0 ml) to increase the palatability of oral dosage forms. sv (1, 2 ) .
1, 2, 9, 10-tetramethoxyaporphine phosphate (MDL-832) was once considered a potential human antitussive. MDL-832 was administered orally in the diets of Sprague-Dawley rats at dose levels of 0, 5, 10, 20, 40, 80 and 160 mg/kg/day for 3 and 6 months and in gelatin capsules to Beagle dogs at 0, 5, 10, 15, 30 and 60 mg/kg/day for 3, 6 and 12 months. Histopathologic examinations of hematoxylin and eosin-stained cerebellar sections revealed intracytoplasmic brown pigment accumulations in large fusiform neurons (presumably the motor type) of the pons. The pigment granules were found to be PAS-positive, non-acid fast, iron-free, Sudan B-positive and fuchsinophilic. Intraneuronal pigment accumulations were seen in rats after 3 months of treatment at 80 mg but not at 40 mg and after 6 months at 20 mg but not at 10 mg. For dogs the effect was observed after 3 months at 60 mg but not at 30 mg and after 12 months at 10 mg but not at 5 mg.
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