The novel type B MAO inhibitor PF9601N enhances the duration of L-DOPA-induced contralateral turning in 6-hydroxydopamine lesioned rats

Summary. The present study examined the effect of the highly potent and selective MAO B inhibitor PF9601N on L-DOPA-induced rotational behavior in unilateral nigrostriatal 6-hydroxydopamine lesioned rats. Three doses of PF9601N (20, 40 and 60 mg/kg) were administered 30 min before an injection of L-DOPA (25 mg/kg), and both contralateral and ipsilateral rotational behavior was measured. In addition, we also studied the effect produced by another MAO B inhibitor, deprenyl (20 mg/kg), the MAO A inhibitor, clorgyline (20 mg/kg), and the dopamine reuptake inhibitor, GBR2909 (7.5 mg/kg) on L-DOPA-induced rotational behavior. The results showed that PF9601N plus L-DOPA significantly enhanced the duration of contralateral rotational behavior with respect to L-DOPA plus vehicle in a dose-related manner. At the dose of 40 and 60 mg/kg, PF9601N produced significantly more overall contralateral turning than L-DOPA plus vehicle, and at the dose of 60 mg/kg, PF9601N produced significantly more turning behavior than L-DOPA plus deprenyl. These results suggest that PF9601N may be used as a novel tool in the treatment of Parkinson's disease. Received March 18, 1999; accepted September 23, 1999     

The efficacy of diflunisal in osteoarthritis of the knee. A Canadian Multicenter Study

Diflunisal, a long acting antiinflammatory analgesic was compared in high (1000 mg daily) and low (750 mg daily) doses with placebo in a randomized, double blind study of 6 weeks' duration in patients with osteoarthritis of the knee. Two hundred twenty-seven patients from 47 centers completed the study--high dose 69, low dose 88 and placebo 70. Pain relief was significantly greater with both doses of diflunisal than with placebo. Both patient and investigator global opinions reflected significantly greater efficacy with diflunisal. Although there was a trend in favour of the higher dose, no statistically significant differences in efficacy were found between the 2 doses of diflunisal studied. Overall adverse reactions with diflunisal were no more frequent than with placebo, but gastrointestinal side effects were significantly greater with the higher dose.     

Reversal of guanethidine blockade of sympathetic nerve terminals by tetraethylammonium and 4-aminopyridine

1 The effect of tetraethylammonium (TEA) and 4-aminopyridine (4-AP) on the inhibitory effect of guanethidine on noradrenaline (NA) release was investigated in the perfused spleen of the cat. 2 Guanethidine blocked the release of NA evoked by nerve stimulation. TEA and 4-AP readily reversed this inhibitory effect, and the NA output was nearly doubled after repeated stimulation of the nerves. On subsequent perfusion with Krebs solution without TEA or 4-AP, the inhibitory effect of guanethidine reappeared. 3 The reversal of guanethidine blockade of sympathetic nerves by TEA and 4-AP is discussed.     

Neuropraxia of the palmar cutaneous branch of the ulnar nerve during carpal tunnel decompression

Carpal tunnel syndrome is one of the most commonly encountered conditions in the hand clinic and carpal tunnel decompression is the most frequently performed procedure in hand surgery. It is an effective procedure for patients with carpal tunnel syndrome. However, there is a high risk of complications that can be avoided with an understanding of wrist anatomy, appropriate planning and execution. We highlight one such complication, a case of neuropraxia of the palmar cutaneous branch of the ulnar nerve that followed carpal tunnel decompression.     

Th1 and Th2 lymphocyte migration across the human BBB is specifically regulated by interferon beta and copolymer-1

Lymphocyte migration into the central nervous system is a central event in lesion formation in MS. Both interferon beta (IFNbeta) and copolymer-1 (Cop-1) reduce the overall lymphocyte entry into the brain through the blood-brain barrier (BBB) as judged by MRI based studies. In this study, we used a modified Boyden chamber assay in which human brain microvascular endothelial cell (HBEC) monolayers are grown on a fibronectin coated transwell membrane to evaluate in vitro migration of allo-antigen Th1 and Th2 lymphocytes across brain endothelium. We confirmed previous observations showing that migration rates of Th2 lymphocytes across HBECs were higher than migration rates of Th1 cells. When HBECs were pre-treated with IFNbeta (100 U/ml) 30 min prior to migration, the migration rate of Th1 was significantly decreased (45% reduction) while the migration of Th2 remained unchanged. Addition of Cop-1 (30 microg/ml) to HBEC monolayers 30 min prior to migration significantly increased the migration rate of Th2 cells and did not affect the migration of Th1 cells. We did not observe any changes in (1) the expression of adhesion molecules on the surface of HBECs and (2) the pattern of chemokine production by HBECs after IFNbeta or Cop-1 treatment. The changes in cellular migration rates were not paralleled with changes in diffusion of large molecular weight tracers across brain ECs. Our data support the notion that immuno-modulators used for the treatment of MS selectively and differentially regulate the migration of T helper lymphocyte subsets and that Cop-1 promotes trans-endothelial migration of Th2 cells across the BBB.