Testing lazaroids U-74389G and U-83836E for therapeutic value in experimental allergic encephalomyelitis in the Lewis rat.

Reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI) are toxic molecules that are thought to play a pathogenic role in many disease states, and data from prior studies indicate a role for ROI and RNI in the pathogenesis of experimental allergic encephalomyelitis (EAE). ROI and RNI can elicit tissue damage by initiating the chain reaction of lipid peroxidation. Lazaroids are a series of compounds that have been shown to interrupt lipid peroxidation. In the present study, the lazaroids, U-74389G and U-83836E, were administered to Lewis rats with EAE in order to evaluate their therapeutic effectiveness. Several different doses and administration routes, which were based on the manufacturer's (Upjohn) recommendations and a prior experimental study, were employed: 1) intraperitoneal injection (IP), 1mg drug/kg body weight, 1x/day from 7-18 days postencephalitogen injection (diseases onset approximately 9 day), male; 2) IP, 1mg/kg, 1x/day from 0-18 days, male; 3) intravenous (IV) cannula, 3mg/kg, 2x/day from 7-18 days, female; 4) IV cannula, 3mg/kg, 2x/day from 7-18 days, male; and 5) IV cannula, 10mg/kg, 2x/day from 7-18 days, female. The weights and clinical signs were evaluated on a daily basis. In all treatment regimens, there was an absence of a statistically significant difference between the vehicle-treated animals and the two groups of drug-treated animals. These data imply that lipid peroxidation may not be an effective therapeutic site in EAE. It is important to note that there are several different types of EAE and our study only explored the EAE model in the Lewis rat.(ABSTRACT TRUNCATED AT 250 WORDS)

Nasal mast cells: a preliminary report on their ultrastructure.

The ultrastructure of mast cells found in normal inferior turbinate was compared with the features found in the inferior turbinate in two groups of patients, those with allergic rhinitis due to dust mite hypersensitivity and those with nasal polyps; the latter group also had their polyps studied. Adenoid tissue was examined in children with secretory otitis media to see if there was evidence of mast cell degranulation, which would support the hypothesis that either local allergic or other mast cell-mediated reactions caused the condition. The mast cells from five normal turbinates varied considerably in size, shape and distribution, but were found mainly in the submucosa. There was no difference in the morphology of cells of different sizes and they could not be sub-grouped into either connective tissue or mucosal mast cells. Most granules were electron dense and homogeneous, although scrolls and crystalline structures were seen occasionally. Some of the granules contained lighter material and others had become vacuoles. Mitochondria were present in all cells suggesting active metabolism. The three patients with allergic rhinitis showed extensive but variable degranulation of the mast cells in all depths of the mucosa. Nine of the 10 cases with nasal polyps had mast cells identified in both the polyp and the turbinate. They were only normal in one turbinate and in one patient it was impossible to identify mast cells. All the mast cells were degranulated extensively in all other specimens. The adenoids from seven children had identifiable mast cells, which were less frequently found than in the turbinates. There was some degranulation in four of the patients and in one it was fairly extensive.