The neuronal ceroid-lipofuscinoses (NCLs) are a group of recessively inhented neurodegenerative lysosomal storage diseases, the pathogenesis of which is unknown. In the present study, we have rneasured iron and w p e r in cerebrospinal fluids (CSF) using methods that detect these metals in a "loosely bound" form, complexable to the chelators bleomycin and 1,1 O-phenanthroline. We studied 25 children with NCL, 21 children with encephalopathy of sorne other type, and 5 control children without neurological complications. The CSF concentrations of loosely bound iron at neutral pH values and of loosely bound copper did not correlate with the clinical diagnosis of the patients, nor did they parallel degenerative symptoms in NCL, such as mental irnpairrnent, visual loss, motor handicap, and epilepsy. However, the concentrations of loosely bound iron and copper increased significantly with the age of the patient; this is a novel finding and may represent increasing tissue destruction with age. Our present findings do not s u p p t a major role for primary iron toxicity in the developrnent of neuronal degeneration. To investigate any secondary pathological role for malplaced transition rnetals, further research is required.
The effect of ethanol on the adsorption of aspirin, quinidine and amitriptyline to activated charcoal was studied in vitro at pH 1.2 and 7.0. The adsorption of these drugs was greatly dependent on the charcoal-drug ratio and on the pH. Ethanol (10%) significantly (P<0.001) increased the percentage of their unadsorbed fraction at both pHs in vitro. In six healthy volunteers activated chiircoal (50 g), ingested 5 min. after aspirin (1000 mg) and quinidine sulfate (200 mg), reduced their bioavailability by about 70% (aspirin) and 99% (quinidine). A significant desorption of aspirin but not that of quinidine from charcoal was obvious on the second and third days and seemed to be related to the effect of pH. The absorption of' ethanol was not significantly prevented by charcoal. The concomitant ingestion of alcohol (50 g) with drugs antagonized only slightly the ability of charcoal to reduce the absorption of aspirin and quinidine.A'cy-words: Activated charcoalethanolaspirinquinidineamitriptylinein virroman
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