Reduction of oxidative stress in amyotrophic lateral sclerosis following pramipexole treatment.

Oxidative abnormalities have been identified both in familial amyotrophic lateral sclerosis (FALS) and the more prevalent sporadic ALS (SALS). Mitochondria dysfunction and toxic free radicals may play a role in this disease process, although the exact pathogenesis of both forms of ALS remains unknown. 2,3-DHBA is a hydroxylated salicylate by product that has been shown to be a reliable marker of increased free radical activity and is reliably assayed by HPLC. Following an oral salicylate load, we found elevated serum levels of 2, 3-dihydroxybenzoic acid (2,3-DHBA) and DHBA/salicylate in SALS subjects. Pramipexole has been shown to reduce oxidative stress and be neuroprotective in cell and animal models of neurodegeneration. We studied 12 SALS patients to determine the levels of 2,3-DHBA both before and after treatment with pramipexole. We found that pramipexole treatment up to 6 mg/day was well tolerated. The mean 2,3-DHBA serum levels were reduced by 45% and DHBA/salicylate ratios declined by 59% following treatment with pramipexole. SALS patients show apparent increases in systemic oxygen radical production that are reduced by pramipexole treatment at conventional doses, suggesting that pramipexole or related compounds may interrupt free radical production in SALS.

Effects of sterilizing gamma irradiation on bloodspot newborn screening tests and whole blood cyclosporine and tacrolimus measurements.

Sterilizing irradiation of the US mail has been proposed as a method to prevent delivery of viable anthrax spores. Because newborn screening samples (bloodspots) and cyclosporine and tacrolimus specimens (whole blood) are delivered routinely through the mail, we studied whether sterilizing gamma irradiation could affect these test results. Specimens were exposed to 18 kGy gamma irradiation (100 hours x 18,000 rad/h), a "kill dose" for Bacillus pumilus spore strips. Irradiation had no significant effect on whole blood cyclosporine or tacrolimus results, but it had a degradative effect on bloodspot phenylalanine, hemoglobins, biotinidase, galactose-1-phosphate uridyltransferase, thyroxine, and thyrotropin. Such irradiation potentially could cause false-negative results for the detection of phenylketonuria and likely would lead to an increase in secondary testing for hemoglobin variants, but it is unlikely to lead to false-negative or false-positive results for the remaining newborn screening tests. These experiments cannot rule out possible greater effects by larger doses or other types of irradiation.