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Suppression of arthritis by an active center analogue of Cu2Zn2-superoxide dismutase (1994)

Miesel, R. ; Dietrich, A. ; Brandl, B. ; [et al.]

Springer

Rheumatology international 14 (1994), S. 119-126

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ISSN: 1437-160X

Keywords: Active center analogues of superoxide dismutase ; Collagen type II-induced arthritis ; Potassium peroxochromate arthritis ; Autoimmunity ; Chemiluminescence ; Inhibition of tumor necrosis factor alpha ; Reactive oxygen species

Source: Springer Online Journal Archives 1860-2000

Topics: Medicine

Notes: Abstract The anti-arthritic and anti-inflammatory efficacy of CuPu(Py)2 {[N, N′-bis(2-pyridylmethylene)-1,4-butanediamine] (N, N′, N″, N‴)}-Cu(II), a serum-stable active center analogue of Cu2Zn2-superoxide dismutase (SOD; EC 1.15.1.1), was tested in male DBA/1xB10A (4R) mice suffering from potassium-peroxochromate-induced (PIA) or collagen type II-induced arthritis (CIA). Parameters including the arthritis index, the plasma SOD activity, and the inhibition of phagocytic responses in unseparated blood were used for the assessment of disease activity. A dose-dependent suppression of arthritis was noted in both models. The ED50 was 2.5±0.4 μmol/kg/day of CuPu(Py)2 for PIA and 4.0±1.1 μmol/kg/day for CIA. The arthritis index correlated with both the levels of reactive oxygen species (ROS) generated by phorbol ester-activated neutrophils and monocytes in unseparated blood (r=0.892) and the SOD-like activity in plasma (r=0.857). CuPu(Py)2 inhibited also the lipoplysaccharide-induced release of tumor necrosis factor alpha from human monocytes and neutrophils in a dose-dependent manner. Unlike SOD, which exerts successful anti-rheumatic activity mainly upon intra-articular injection, the SOD-mimic CuPu(Py)2 can be applied systemically. Non-proteinaceous low molecular weight antioxidases may well be suited to control oxidative stress-derived damage in rheumatic diseases by modulation of ROS-dependent signal transduction pathways.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF00300814

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Em-tomography of section collapse, a non-linear phenomenon (1995)

van Marle, J. ; Dietrich, A. ; Jonges, K. ; [et al.]

New York, NY [u.a.] : Wiley-Blackwell

Microscopy Research and Technique 31 (1995), S. 311-316

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ISSN: 1059-910X

Keywords: EM-tomography ; Reconstructions ; Back projection ; Section collapse ; Distortion of Z dimensions ; Life and Medical Sciences ; Cell & Developmental Biology

Source: Wiley InterScience Backfile Collection 1832-2000

Topics: Natural Sciences in General

Notes: Using back projection for reconstruction and tilt series of Epon or Lowicryl embedded and sectioned material, we demonstrated: (1) a reduction in thickness of 50% for Epon and 80% for Lowicryl sections, and (2) a non-uniform density distribution along the electron-optical axis in sections. The highest density was found at the vacuum exposed side of the section. The formvar side of the section showed a similar increase in density, but not to the same extent. Minimalization of electron exposure, even without pre-exposure, did not affect the reconstructed thickness, nor did it affect the non-uniform density distribution. However, parallax measurements showed that at 150K, collapse of Epon sections does not take place. For EM-tomography of plastic embedded material our findings imply that at the top and bottom portion of the sections the dimensions of the reconstructed structures are distorted, but that in the middle portion the dimensions are reliably retained. © 1995 Wiley-Liss, Inc.

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