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.

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The current experiment was performed to examine the acute and cumulative effects of chronic manual teat stimulation on the tonic pattern of luteinizing hormone (LH) secretion in beef cows. Additionally, we characterized the plasma profile of prolactin and cortisol release to evaluate whether changes in the concentrations of these hormones occurred in response to teat stimulation and whether such changes were related to gonadotropin secretion. Six weeks after ovariectomy, nonlactating beef females were paired by age and assigned randomly to a control group (n = 3) or a stimulation group (n = 3). Stimulated cows were subjected to 20 min of continuous manual teat stripping every 4 h for 24 h. Blood samples were collected from all cows at 10-min intervals beginning 1 h before and continuing for 2 h after the onset of each stimulation period in treated animals. Numerous episodes of prolactin and cortisol release were observed in control and treated animals throughout the 24-h experiment. The percentage of stimulations accompanied by prolactin and cortisol releases for each of the three treated animals was 100 and 100, 16.7 and 50, and 50 and 100, respectively. The number of prolactin peaks observed the hour after onset of teat stimulation was greater (P less than .06) than the number observed the hour before. However, the number of cortisol peaks was not statistically related to teat stimulation. Overall, mean concentrations of prolactin and cortisol were not increased by teat stimulation. Luteinizing hormone pulse frequency (1.6 +/- .1 pulses/h) and mean LH concentrations (12.1 +/- .6 ng/ml) were not acutely or chronically affected by teat stimulation and were not related to prolactin or cortisol release. We conclude that mechanical stimulation of the teat is not singly effective in altering the pattern or quantity of tonic LH release in ovariectomized cows.

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.