Background: The aim of the study was to determine pregnancy-associated plasma protein-A (PAPP-A), which was recently described as a new marker of cardiovascular events, in patients with chronic renal insufficiency/failure and to find out its relationship to renal function and to prominent markers of oxidative stress (advanced oxidation protein products – AOPP) and inflammation (C-reactive protein – CRP). Methods: The studied group consisted of 36 chronic hemodialysis patients (HD), 10 patients treated with continuous ambulatory peritoneal dialysis (CAPD) and 38 patients with chronic renal insufficiency (CHRI) not yet dialyzed. PAPP-A was measured by Time Resolved Amplified Cryptate Emission technology. Determination of AOPP is based on a spectrophotometric method. Results: PAPP-A levels are statistically significantly elevated in the both groups of dialyzed patients in comparison with healthy subjects (27.0 ± 16.5 mIU/l in HD and 14.07 ± 6.73 mIU/l in CAPD vs. 8.22 ± 2.7 mIU/l in the control group, p < 0.0001 and p < 0.001, respectively, p < 0.05 HD vs. CAPD). The mean serum PAPP-A levels in the CHRI patients not yet dialyzed were not significantly higher in comparison with the control group (9.72 ±4.44 vs. 8.22 ± 2.7 mIU/l, n.s.). In the CHRI not dialyzed patients, we found a significant positive correlation between serum creatinine and PAPP-A levels (r = 0.68, p < 0.05). In comparison with controls, AOPP and CRP levels were significantly higher in HD patients [AOPP 155.0 ± 37.9 µmol/l, p < 0.0001 vs. controls, CRP 10.0 (4.6– 26.9) mg/l (median, interquartile range), p < 0.0001 vs. controls], CAPD patients [AOPP 118.5 ± 25.8 µmol/l, p < 0.0001 vs. controls, CRP 7.7 (2.0–18.8) mg/l, p < 0.01 vs. controls] and AOPP levels in chronic renal failure patients not yet dialyzed (98.5 ± 43.24 µmol/l, p < 0.01 vs. controls). The correlations between PAPP-A and AOPP (r = 0.49, p < 0.05) and PAPP-A and CRP (r = 0.48, p < 0.05) serum concentration were statistically significant in HD patients. In CAPD patients, neither a correlation between PAPP-A and AOPP nor a correlation between PAPP-A and CRP were found. Conclusion: We can conclude that serum PAPP-A levels sensitively reflect the changes in renal function, depend on dialysis modality, and may represent a novel marker associated with inflammation and oxidative stress in chronic renal failure patients.

Background: Increased serum levels of proinflammatory cytokines may contribute to the organ damage in active antineutrophil cytoplasmic antigen (ANCA)-positive renal vasculitis. Plasma exchange (PE) may influence the activity of vasculitis not only by removing pathogenic autoantibodies, but also by lowering the serum levels of circulating cytokines. Methods: Serum levels of IL-1β, IL-1ra, IL-6, IL-8, ICAM-1 and VCAM-1 were measured using ELISA in 10 patients with active ANCA-positive renal vasculitis (5 patients with Wegener’s granulomatosis, WG, and 5 patients with microscopic polyangiitis, MPA) during the course of therapeutic PE. Cytokines and adhesion molecules were measured in samples of serum obtained at the beginning and at the end of the 1st, 3rd and 5th PE and in samples of filtrate obtained during the same PE. Results: In comparison with controls, patients with ANCA had higher serum levels of IL-1ra, IL-8, ICAM-1 and VCAM-1 before the 1st PE. Serum levels of IL-6, IL-8, ICAM-1 and VCAM-1 were increased in patients with MPA, and the serum levels of all the cytokines and adhesion molecules measured in patients with WG were increased. At the end of the PE course there were decreases in the serum levels of IL-1ra and VCAM-1 in ANCA patients and IL-1ra and ICAM-1 in WG patients. Single PE in ANCA patients led only to a decrease in serum levels of ICAM-1 and VCAM-1. On the other hand, there was no change in serum levels of IL-1β and IL-8, and the serum levels of IL-1ra and IL-6 even increased at the end of a single PE, in spite of high levels of all cytokines and adhesion molecules in the plasma filtrate. Conclusion: Serum levels of soluble adhesion molecules decrease after PE, but serum levels of proinflammatory cytokines are not reduced even by a PE course. Removal of these substances by PE is obviously counteracted by their increased production, possibly further stimulated by the contact of blood with the synthetic membrane. The insufficient influence of PE on the elimination of proinflammatory cytokines may partially explain its limited effect in some patients with ANCA-positive renal vasculitis.

No abstract

Plasma exchange (PE) is an effective therapeutic method used in patients with myasthenia gravis (MG) refractory to common therapy and/or with life-threatening respiratory complications. Except for acetylcholine receptor antibodies (AChRAbs), some other inflammatory mediators possibly activated in MG may also be removed during PE. Serum levels of soluble adhesion molecules (sICAM-1 and sVCAM-1), IL-6 and soluble receptors for IL-2 (sIL-2R), IL-6 (sIL-6R) and TNFα (sTNF-R II) were measured in 20 MG patients assigned to treatment with PE. On the basis of the serum levels of AChRAb the patients were subdivided into 2 groups (8 patients with low AChRAb, 12 patients with high AChRAb). Soluble adhesion molecules and cytokines were measured before the first and last PE, at the end of the first PE and in the samples of plasma filtrate obtained during the first PE. Before the first PE patients with MG had higher serum levels of sICAM-1, sVCAM-1, sIL-2R and sTNF-R II than controls. Both after the first PE and during the course of PE, a substantial decrease in serum levels of AChRAb, sICAM-1 and sVCAM-1 was recorded. However, serum levels of sIL-2R and sTNF-R II were not significantly influenced by either a single treatment or during the course of PE. There were high levels of AChRAb, soluble adhesion molecules and soluble cytokine receptors in plasma filtrates too. Patients with high circulating AChRAb had higher serum levels of sICAM-1 and sVCAM-1 than patients with low AChRAb. Increased serum levels of soluble adhesion molecules and soluble cytokine receptors in patients with MG suggest some systemic activation of the immune response which is more pronounced in patients with high circulating AChRAb. PE led to the decrease in serum AChRAb and soluble adhesion molecules due to their effective filtration but, on the other hand, serum levels of soluble cytokine receptors were not influenced by PE, in spite of their effective filtration which is probably counteracted by their increased production, possibly stimulated by the contact of the blood with the synthetic membrane.

We present several polynomial-time algorithms for c-planarity testing for cluster hierarchy C containing clusters of size at most three. The main result is an O(|C| 3 + n)-time algorithm for clusters of size at most three on a cycle. The result is then generalized to a special class of Eulerian graphs, namely graphs obtained from a 3-connected planar graph of fixed size k by multiplying and then subdividing edges. An O(3 k · k · n 3 )-time algorithm is presented. We further give an O(|C| 2 + n)-time algorithm for general 3-connected planar graphs.