allopurinol and Uveitis

We report an unusual case of leishmaniosis with the involvement of mammary glands in an old cat with what seems to be a concurrent regressive feline leukemia virus infection. Leishmania donovani complex parasites were identified for the first time in inflammatory breast fluid during a clinical recurrence manifested about 4 years after the first diagnosis of feline leishmaniosis. Combined treatment with allopurinol and meglumine antimoniate resulted in clinical cure of mammary lesion and a concurrent uveitis.

Topics: Allopurinol; Animals; Antiprotozoal Agents; Cat Diseases; Cats; Female; Leishmania donovani; Leishmaniasis; Leukemia Virus, Feline; Leukemia, Feline; Mammary Glands, Animal; Meglumine Antimoniate; Portugal; Uveitis

Topics: Allopurinol; Animals; Autoimmune Diseases; Down-Regulation; Immunologic Factors; Intercellular Adhesion Molecule-1; Purinergic P2 Receptor Antagonists; Receptors, Purinergic P2; Receptors, Purinergic P2X7; Tumor Necrosis Factor-alpha; Uveitis

Allopurinol shows beneficial effects in the systemic treatment of lens-induced uveitis. This is believed to be due to the reduction of oxidative tissue damage via a dose-dependent free radical scavenging ability and an immunomodulating effect. The purpose of this study was to investigate the immunological effects in experimental autoimmune uveitis after systemic treatment with allopurinol (AL) and steroids (STER).. 31 male Lewis rats were immunized with crude retinal extract, Freund's Adjuvans and pertussis toxin. The rats were divided into four groups: healthy rats (BASIS, n = 3), experimental autoimmune-uveitis without therapy (EAU, n = 9), 50 mg/kg bw. allopurinol i.v. (ALSYS, n = 9), and 7.5 mg/kg bw. methylprednisolone i.v. (STSYS, n = 10). ALSYS and STSYS received five intravenous injections during the 2 weeks immunization period. The rats' sera were tested against Western Blots (WB) of electrophoretic separations of retinal proteins. Based on digital image analysis, an analysis of discriminance was performed.. The multivariate analysis of discriminance revealed a significance difference between the WBs of ALSYS and STSYS (p < 0.01) compared to EAU without therapy. The number and intensity of peaks in WBs were strongly reduced in the ALSYS group compared to EAU.. AL revealed a strong immunomodulating effect in the treatment of experimental autoimmune uveitis that is markedly stronger than that of steroids. Together with the antioxidative effect of allopurinol known from previous studies, this drug could be a new promising therapeutic approach in the treatment of uveitis.

Topics: Allopurinol; Animals; Anti-Inflammatory Agents; Autoantibodies; Autoimmune Diseases; Blotting, Western; Dose-Response Relationship, Drug; Free Radical Scavengers; Immune Tolerance; Injections, Intravenous; Male; Methylprednisolone; Rats; Rats, Inbred Lew; Retina; Uveitis

We assessed the suppressive effect of a combination of cyclosporin (an immunosuppressive agent) and allopurinol (a xanthine oxidase inhibitor and radical scavenger) on experimental autoimmune uveoretinitis (EAU) in Lewis rats, induced by interphotoreceptor retinoid-binding protein (IRBP).. After the immunization of Lewis rats with 30 micrograms of IRBP. We administrated cyclosporin and/or allopurinol to the IRBP-immunized Lewis rats. We observed the incidence and the severity of EAU. Histological, immunological, and biochemical examinations were performal 13 days after the immunization. The suppressive effect of these drugs in vitro on the production of free radicals derived from polymorphonuclear leukocytes.. The incidence of EAU was suppressed by 50% at 13 days after immunization, and in terms of clinical and histological findings, inflammatory reaction was more inhibited by the combination of these drugs than by either cyclosporin or allopurinol alone. Lymphocyte proliferation assay against IRBP was significantly inhibited by the combination of drugs. No adverse systemic effects were identified. Cyclosporin and allopurinol inhibited radical production both separately and in combination.. This suggests that suppression of EAU is based not only on inhibited cell-mediated immunity but also on inhibited production of free radicals derived from polymorphonuclear leukocytes.

Topics: Allopurinol; Animals; Autoimmune Diseases; Cyclosporine; Free Radical Scavengers; Immunosuppressive Agents; Male; Rats; Rats, Inbred Lew; Retinitis; Uveitis; Xanthine Oxidase

The aim of this study was to evaluate the immunomodulating activity of allopurinol using a model of lens-induced uveitis (LIU) and to compare these effects to those of steroids.. We tested the sera of both LIU and control rats against western blots (WB) of SDS-PAGE separations of protein fractions from normal and LIU rat lenses. These blots were scanned using digital image analysis. A newly developed technique was used to compare the complex autoantibody (AAB) repertoires. Five groups of LIU rats were investigated: no treatment; single doses of methylprednisolone (MPR; 7.5 mg/kg body wt.i.v.); allopurinol (AL; 50 mg/kg body wt. i.v.); a combination of both drugs (AL and MPR); repeated application of AL (ALFR; 50 mg/kg body wt.i.v. every 2 weeks during the immunization period and a daily dose of approx. 25 mg/kg body wt. orally).. Immunization induced complex antibody repertoires against lens proteins. Antibody repertoires of LIU rats were identical, regardless of whether the proteins were obtained from control, uveitis eyes, or corresponding healthy eyes of the same individual. AL showed a dose-dependent immunological effect in LIU treatment. Given as a single dose, AL revealed no significant change in the AAB repertoire; however, ALFR showed very clear modification of the AAB repertoires compared to both controls and rats receiving steroids.. These results suggest dose-dependent effects of allopurinol in LIU treatment. Repeated application during the immunization period induced a strong immunomodulating effect of AL that was not observed after single doses.

Topics: Adjuvants, Immunologic; Allopurinol; Animals; Antimetabolites; Autoantibodies; Autoantigens; Blotting, Western; Crystallins; Dose-Response Relationship, Drug; Drug Administration Routes; Drug Therapy, Combination; Electrophoresis, Polyacrylamide Gel; Glucocorticoids; Male; Methylprednisolone; Rats; Rats, Wistar; Uveitis

The paper presents the case of a serious uveitis not yielding to a conventional therapy. After an insight differential diagnostics it was found that the gout made the disease etiology. After including a specific therapy an improvement in the local status was achieved.

Topics: Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Female; Gout; Gout Suppressants; Humans; Injections, Intramuscular; Middle Aged; Piroxicam; Prednisolone; Uveitis

To evaluate the effects of allopurinol in lens induced uveitis (LIU) by morphological methods and to compare these effects with those of steroids and a combination of both drugs biochemically and morphologically.. Lipid peroxides (LPO) of the retinal tissue were determined by two different methods (thiobarbituric acid assay (TBA) and high performance liquid chromatography expressed as malondialdehyde-like substances). Myeloperoxidase (MPO) activity in the iris/ciliary body complex was analysed spectrophotometrically. Histological changes on three morphological levels of LIU eyes were evaluated.. Both allopurinol and the combination of allopurinol/prednisolone led to a significant reduction in the increaed retinal LPO values. Prednisolone only revealed significant effects on retinal LPO when being measured with the TBA method. MPO activity in iris and ciliary body was significantly reduced in all therapy groups. The morphological evaluation of the sections by two masked investigators revealed a significant reduction (p < 0.05) in the inflammation score in all therapy groups. Morphometric studies using the QUANTIMED system (Leica, Cambridge) showed significantly reduced values (p < 0.05) in the allopurinol group and in the group receiving prednisolone and allopurinol. Prednisolone alone did not lead to a significant reduction in the values.. The findings show that both allopurinol and steroids exert positive effects on the variables determined in LIU. The effects of steroids are believed to be mostly due to their direct action on inflammatory cells. The recently reported scavenging effects of methylprednisolone should play a minor role in this disease model. Allopurinol and oxypurinol act as direct scavengers of free radicals and hypochlorous acid, which is produced via MPO catalysis, thus leading to a reduction in tissue inflammation and tissue damage.

Topics: Allopurinol; Animals; Anti-Inflammatory Agents; Chromatography, High Pressure Liquid; Ciliary Body; Contact Lenses; Disease Models, Animal; Drug Therapy, Combination; Free Radical Scavengers; Image Processing, Computer-Assisted; Iris; Lipid Peroxides; Male; Peroxidase; Prednisolone; Rats; Rats, Wistar; Retina; Uveitis

Topics: Animals; Eye Proteins; Leukocyte Count; Rats; Transferrin; Uveitis; Xanthine Oxidase

In addition to the inhibition of xanthine oxidase, allopurinol is known to act, dependent on the dose, as a free radical scavenger, an antioxidant, and a "scavenger" of hypochlorous acid. This activity was investigated using a model of lens-induced uveitis.. Lipid peroxides (LPO) were determined in aqueous humor and in retinal tissue. Reduced and oxidized glutathione (GSH and GSSG) of the aqueous humor and myeloperoxidase (MPO) activity in the iris-ciliary body complex were analyzed. Allopurinol and oxypurinol concentrations were determined by high-performance liquid chromatography in aqueous humor and retinal tissue of both control eyes and eyes with uveitis. These measurements were performed 6 hours after intravenous application of allopurinol.. In lens-induced uveitis, LPO are significantly elevated, GSH is reduced, and GSSG and MPO are increased. A xanthine oxidase inhibition dose (< 10 mg/kg body weight) of allopurinol showed no effects on oxidative tissue damage in the model used in this study. Higher doses, however, were able to reduce the oxidative damage. Allopurinol (20 mg/kg body weight) had slight effects on GSH and GSSG. All parameters improved using a dose of 50 mg/kg body weight; a dose of 100 mg/kg body weight only showed additional improvement in GSH and GSSG. There was no further change in the other parameters. Allopurinol and oxypurinol concentrations in aqueous humor and retinal tissue showed a dose dependency reaching scavenger concentrations after application of 50 mg/kg body weight of allopurinol.. These results suggest that the xanthine oxidase mechanism plays a minor role in the oxidative tissue damage due to lens-induced uveitis. Free radicals and oxidants are generated by activated leukocytes; therefore, the effect of higher doses of allopurinol is due to its free radical scavenging and antioxidative activity.

Topics: Allopurinol; Animals; Anterior Eye Segment; Antioxidants; Chromatography, High Pressure Liquid; Crystallins; Disease Models, Animal; Dose-Response Relationship, Drug; Free Radical Scavengers; Glutathione; Lens, Crystalline; Lipid Peroxides; Male; Oxypurinol; Peroxidase; Rats; Rats, Wistar; Retina; Uveitis

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Dexamethasone; Free Radical Scavengers; Free Radicals; In Vitro Techniques; Indomethacin; Iron; Liposomes; Male; Oxygen Consumption; Peroxides; Phosphatidylcholines; Rabbits; Superoxides; Thiazoles; Uveitis; Xanthine Oxidase

Lodoxamide, a xanthine oxidase inhibitor, has antiphlogistic effects in the treatment of acute uveitis. The role of xanthine oxidase generated free radicals is discussed.

Topics: Animals; Disease Models, Animal; Drug Evaluation; Endophthalmitis; Oxamic Acid; Rats; Superoxides; Uveitis; Xanthine Oxidase

Intravitreal injection of a superoxide-generating reaction mixture of xanthine oxidase and xanthine, either with or without rabbit plasma, was shown to be a mediator of an intense uveal and retinal inflammation in pigmented and albino rabbits. Controls of heat-inactivated xanthine oxidase with or without rabbit plasma, or plasma by itself, was without effect on ocular tissues. Xanthine alone as a control exhibited little or no inflammatory response. Controls of active xanthine oxidase by itself, or with rabbit plasma, produced a very strong inflammatory response that may represent enzymic reaction with endogenous xanthine. When the superoxide generating reaction mixture was given intravitreally the reaction began in the anterior segment within 16 hours and reached its peak after 2 days. The response in the posterior segment was delayed and did not become evident until after at least 24 hours, and may be due to the close proximity of the anterior chamber to the ciliary processes where cellular exudates first appear. Anterior segment uveitis began to recede after 4 days but posterior segment inflammation persisted beyond 6 days, and in many instances, led to retinitis, and retinal detachment. Superoxide dismutase was effectively used in vitro to quench superoxide in the reaction mixture but it did not prevent inflammatory reactions in vivo because it was found to possess strong toxic qualities of its own in ocular tissues. Other free radicals of oxygen, as well as hydrogen peroxide, can develop with the breakdown of superoxide, and cause tissue damage. A known ability of superoxide to convert a plasma precursor into a factor chemotactic for neutrophils may also cause superoxide production in situ by accumulating neutrophils. Because phagocytes are potential sources of superoxide, this study provides a good experimental model for studying the influence of oxygen free radicals in ocular inflammatory disease.

Topics: Animals; Female; Free Radicals; Male; Rabbits; Retinitis; Superoxides; Uveitis; Xanthine; Xanthine Oxidase; Xanthines