The antiinflammatory efficacy of CuPu(Py)2 ([[N,N'-bis(2-pyridylmethylene)-1,4-butanediamine] (N,N',N'',N''')]-Cu2+), a serum stable active center analog of Cu2Zn2superoxide dismutase (SOD), was tested in vitro and in vivo in male Wistar rats suffering from potassium peroxochromate-induced inflammation. Parameters including 99mTc gamma-scintigraphic imaging, the arthritis score, the plasma superoxide dismutase activity, the inhibition of plasma sulfhydryl depletion as well as mitogenic and phagocytic responses were used to quantify the disease activity. All parameters improved impressively during the treatment with CuPu(Py)2 and resembled those of healthy animals after 21 days. The arthritis score was inhibited by 80% (P > 0.001) and the plasma SOD activity enhanced by 380% (P > 0.001). The depletion of plasma sulfhydryls and the leukocytic responses to concanavalin A, tetradecanoylphorbolacetate, and lipopolysaccharide were significantly reduced (P > 0.001) and correlated well with the arthritis score. The collapse of antioxidant defenses in human plasma as well as the depolymerization of hyaluronic acid was mimicked in vitro and successfully inhibited by CuPu(Py)2. Oxidant-induced injury of plasma components during the aqueous decay of potassium peroxochromate were demonstrated to activate the oxidative burst of phagocytes in human blood. The role of impaired pro- and antioxidant balances in the etiology of inflammatory and autoimmune rheumatic diseases is discussed.
The total radical-trapping antioxidative capacity (TRAC) of plasma was evaluated in samples from patients suffering from various inflammatory and autoimmune rheumatic diseases (n=104) and correlated with the phorbol ester-stimulated chemiluminescence (CL) of neutrophils and monocytes in unseparated blood. Plasma and blood samples from age- and sex-matched healthy volunteers (n=25) and from patients with non-rheumatic internal diseases (n=31) served as controls. A 2 to 10 fold increase in whole blood chemiluminescence was found in rheumatic patients, which paralleled 50-80% decreased levels of plasma TRAC-values. While significant correlations between CL and TRAC were determined for patients with inflammatory arthritic diseases no correlations were found with patients suffering from connective tissue diseases. Prednisolone treatment of individual patients increased plasma TRAC-values substantially and decreased elevated levels of phagocytic CL generation to that of healthy controls. The main potential application of the assays described here is for the convenient assessment of disease activity and progression in individual patients with rheumatic diseases.
The case of a 41/2-year-old girl with disseminated neuroblastoma and concomitant osteomyelitis is reported. Neuroblastoma was detected in the vertebral column, the right suprarenal fossa, the left side of cranium and in bone marrow aspirates. Osteomyelitis was present in the left femur and was due to Salmonella tennessee. For the first time in the literature the two lesions were demonstrated by means of simultaneous 131I-MIBG and 99mTc-DPD scintigraphy. The diagnoses were proved by direct histological and microbiological studies.
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