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The anti-phlogistic effect of dietary vitamin E supplementation on the acute inflammation observed in experimental lens-induced uveitis in Brown Norway rats was studied. The effects of vitamin E were examined using histopathologic parameters as well as by measuring the levels of arachidonic acid metabolites. Histologic examination of the eyes revealed that the vitamin E-deficient animals had the most severe destruction of the retina, while those animals receiving the vitamin E-supplemented diet exhibited the best preservation of the retinal architecture. Levels of arachidonic acid metabolites, as determined by radioimmunoassay, were significantly higher in vitamin E deficient rats as compared with rats on a normal diet.

Anti-inflammatory potentials of a safe, common dietary component, quercetin, were investigated in suppression of intraocular inflammation induced by retinal S antigen. Lewis rats sensitized to S antigen were treated daily with intraperitoneal injections of quercetin. Control rats with S-antigen-induced uveitis were similarly treated with diluent. When compared with controls the treated group showed marked reduction in uveal and retinal inflammation and in vasculitis and perivasculitis. Morphometric analysis revealed a significant reduction (p less than 0.005) in choroidal thickness when compared with that of control animals. These results clearly show the antiphlogistic effects of quercetin in experimental uveitis.

Modulation of signal transduction at the surface of inflammatory cells appears to influence acute inflammation. Adenosine, a well-known chemical messenger, inhibits the production of superoxide by sti

Dimethyl thiourea is a highly specific hydroxyl radical scavenger. The anti inflammatory potential of this hydroxyl radical scavenger was studied in Lewis rats sensitized with soluble lens protein. Intraperitoneal injection of dimethyl thiourea into the experimental animals at the onset of the disease resulted in marked reduction of intraocular inflammation, hemorrhage and edema, and eliminated the retinal and choroidal necrotizing vasculitis that was characteristic in untreated animals. These findings indicate that dimethyl thiourea may act as a potent antiphlogistic agent in the treatment of experimental lens induced uveitis.

In acute inflammation, the tissue damage is generally mediated through polymorphonuclear leukocytes and macrophages. Recent studies on the mechanism of this leukocyte-mediated cytolysis have demonstrated that these cells, on stimulation, release a variety of reactive products. These metabolic products consist of superoxide and hydrogen peroxide, which in turn can form highly reactive species such as hydroxyl radicals. It is believed that these oxygen products play an important role in the tissue damage that occurs in inflammations such as uveitis. The ocular structures contain various antioxidant enzymes that normally protect against free radical mediated injury. In experimental animal models of uveitis, it has been shown that antioxidants and free radical scavengers can function as antiinflammatory agents and can protect the eye from inflammation-mediated tissue damage.

An acute lens-induced necrotizing intraocular inflammation was produced in Lewis rats. Treatment of these animals by intraperitoneal injection of glutathione peroxidase resulted in marked decrease in uveal inflammation, retinal edema, hemorrhage and vasculitis. Intraperitoneal injection of glutathione peroxidase resulted in increased levels of this enzyme in ocular tissue. These findings suggest that glutathione peroxidase can modulate acute lens-induced ocular inflammation by serving as a potent anti-inflammatory agent.

• Lewis rats with retinal S-antigeninduced uveitis were treated with the enzymatic antioxidants superoxide dismutase and catalase or with the hydroxyl radical scavenger dimethyl thiourea for one week. The enucleated eyes of these animals and of normal saline-treated control rats were studied for the presence of lipid peroxidation products in the retina; in addition, choroidal thickness was measured by morphometric analysis to determine the severity of choroidal inflammation. Control animals showed severe chorioretinal inflammation and presence of lipid peroxidation products. Intraocular inflammation was less severe and formation of conjugated dienes and malonaldehyde was significantly inhibited in animals treated with the enzyme antioxidants or dimethyl thiourea. These results suggest that free radicals generated during intraocular inflammation can lead to retinal damage by peroxidation of its lipid cell membranes.

Bacterial membranes present solid-ordered/liquid-disordered (so/ld) cooperative melting event close to physiological temperature. The cellular advantage of this thermotropic melting event is yet to be determined. We show that this thermal behavior provides resistance towards a membrane active antibacterial agent.Phospholipase A2 type IIA (sPLA2-IIA) is a hydrolytic enzyme which presents antibacterial properties towards Gram positive bacteria. The enzyme has higher activity in ld phase compared to so phase in anionic membranes. We show that the lipid phase behavior of Staphylococcus aureus (S.aureus) membranes as measured by FTIR modulates sPLA2-IIA by inducing a sharp drop in activity below the melting temperature of the membrane (centered at 15.3°C).The effects of sPLA2-IIA treatment on cell viability are also investigated. While above the main melting event viability drops to 20% of the initial CFU after treatment, below the main melting event cell viability only drops to 60% under the same treatment. This strongly suggests that cells in the solid-ordered phase are better adapted to survive the enzymatic insult.These results led us to explore if a subpopulation of S.aureus enriched in ordered lipids can be selected after repeated treatment with sPLA2-IIA at 37°C. After selecting for resistance at 37°C we measured growth curves, membrane order, and cell viability as a function of treatment temperature. The results suggest that at 37°C there is a bacterial subpopulation with increased membrane rigidity that insures survival of the colony to an insult by sPLA2-IIA. This subpopulation also presents a longer latency period which can be explained by the increased presence in ordered lipids, which are known to inhibit cell division. Even if the growth conditions are not optimal, the presence of this subpopulation ensures survival from the antibacterial insult.