Bone remodeling is a tightly coupled process consisting of repetitive cycles of bone resorption and formation. Both processes are governed by mechanical signals, which operate in conjunction with local and systemic factors in a discrete anatomic structure designated a basic multicellular unit (BMU). The microenvironment around total joint arthroplasty is a dynamic and complex milieu influenced by the chemical and physical stimuli associated with servicing the prosthesis. A key factor limiting the longevity of the prosthesis is polyethylene wear, which induces particle disease, and this may lead to increased and prolonged activity of BMUs resulting in periprosthetic osteolysis. Several pathways regulating BMU function have been reported in the past, including RANKL/RANK/OPG/TRAF6, TNF-α/TNFR/TRAF1, and IL-6/CD126/JAK/STAT. Moreover, the expression and functional activity of all these molecules can be affected by variations in their genes. These may explain the differences in severity of bone defects or prosthetic failure between patients with similar wear rates and the same prosthesis. Simultaneously, this data strongly support the theory of individual susceptibility to prosthetic failure., J. Gallo, M. Raška, F. Mrázek, M. Petřek., and Obsahuje bibliografii a bibliografické odkazy
Glucocorticoid (GC) therapy is one of the methods of choices for treatment of autoimmune diseases (ADs). In addition, adrenal androgens are known as immunoprotective GC-antagonists. Adrenal steroids preferentially influence the Th1-components over the Th2 ones. We investigated steroid metabolome (using gas chromatography-mass spectrometry) in healthy controls (H), GC-untreated patients with ADs different from IgA nephropathy (U), GC-treated patients with ADs different from IgA nephropathy (T) and in patients with IgA nephropathy (IgAN), which were monitored on the beginning (N0), after one week (N1) and after one month (N2) of prednisolone therapy (60 mg of prednisolone/day/m2 of body surface). Between-group differences were assessed by one-way ANOVA, while the changes during the therapy were evaluated by repeated measures ANOVA. The ANOVA testing was followed by Duncan’s multiple comparisons. IgAN patients and patients with other ADs exhibited lack of adrenal androgens due to attenuated activity of adrenal zona reticularis (ZR). Androgen levels including their 7α-, 7β-, and 16α-hydroxy-metabolites were further restrained by GC-therapy. Based on these results and data from the literature, we addressed the question, whether a combination of GCs with Δ5-steroids or their more stable synthetic derivatives may be optimal for the treatment of antibodies-mediated ADs., I. Šterzl, M. Hill, L. Stárka, M. Velíková, R. Kančeva, J. Jemelková, L. Czerneková, P. Kosztyu, J. Zadražil, K. Matoušovic, K. Vondrák, M. Raška., and Obsahuje bibliografii