Ischaemic stroke and the recanalization drug tissue plasminogen activator interfere with antibacterial phagocyte function.

BACKGROUND: Stroke induces immune alterations such as impaired oxidative burst and reduced release of neutrophil extracellular traps (NETs). We hypothesised that key enzymes of these defence mechanisms may be altered in ischaemic stroke. Therefore, we analysed the intra- and extracellular amounts of myeloperoxidase (MPO) and neutrophil elastase (NE) in patient sera and granulocytes and monocytes. Because the autonomous nervous system is thought to mediate stroke-induced immune alterations, we also studied the influence of stress hormones and acetylcholine on MPO and NE. Rapid recanalization by recombinant tissue plasminogen activator (r-tPA) is the only available treatment for ischaemic stroke besides thrombectomy, and its influence on antibacterial defence mechanisms of granulocytes and monocytes were addressed here. METHODS: Ex vivo: Intracellular and serum MPO and NE were measured on days 0, 1, 3 and 5 post-stroke by either flow cytometry or enzyme-linked immunosorbent assay (ELISA) and compared to controls. In vitro: Blood from healthy donors was incubated with catecholamines, dexamethasone and acetylcholine, and the percentage of NET-producing cells and the area covered by NETs were quantified immunohistochemically. Intra- and extracellular MPO and NE were quantified by flow cytometry or ELISA. Blood samples from healthy donors were incubated with r-tPA, and oxidative burst, phagocytosis, NETosis, cytokine release, MPO and NE were quantified by flow cytometry, ELISA and microscopy. RESULTS: MPO was reduced in granulocytes but increased in sera obtained from stroke patients compared to controls. NE was not altered intracellularly but was elevated in patient sera. The percentage of NET-producing neutrophils was decreased by stress hormones and increased by acetylcholine. Neither intracellular MPO nor NE was altered by hormone treatment; however, adrenaline and acetylcholine induced NE release. r-tPA led to reduced phagocytosis and oxidative burst in granulocytes and monocytes in vitro. NETosis, MPO release and cytokines were not altered, whereas NE release was enhanced by r-tPA. CONCLUSIONS: Intracellular reduction of MPO might be responsible for reduced NETosis in stroke patients. The impact of enhanced MPO and NE serum levels in stroke patients should be addressed in future studies. r-tPA impaired antibacterial defence function in vitro. Therefore, patients who undergo unsuccessful recanalization therapy might be at higher risk for infection, which should be analysed in future investigations. Immune alterations due to r-tPA effects in stroke patients should also be investigated.

[Histopathological diagnostics for assessment questions of tendo-, ligamento-, and meniscus pathologies]. / Histopathologische Diagnostik bei Begutachtungsfragen von Tendo­, Ligamento- und Meniskuspathologien.

This review article presents the possibilities and limitations of histopathological diagnostics on the issues of joint diseases, including in the context of the medical insurance inquiries, which consider the important articular, non-osseous compartments, especially of the tendons, ligaments, and meniscus. Essential for expert assessments is the causal clarification of whether the continuity disruption has been induced exogenously by trauma or endogenously based on tissue that is functionally impaired and thus degeneratively altered. The degree of degeneration/texture disorder is determined by means of the degeneration-score, which is set in a semiquantitative, three-stage grading. Grades 1 and 2 are summed up as low-grade degeneration and compared to grade 3, high-grade degeneration. Age determination of continuity disruption is based on the assessment of the morphology of discontinuity and on the assessment of hemosiderin deposits. The tasks of histopathological diagnostics thus consist of the detection and grading of textural disorder (degeneration), the determination of the histopathologic age of existing continuity disruptions, and particularly the diagnosis of clinically/radiologically undiagnosed diseases, which may be relevant for pathogenesis. In the case of contradictory diagnoses from different diagnostic disciplines and in the case of imprecise and potentially even contradictory patient information, purely legal, judicial decisions may be necessary. In this case the legally binding assessment within the framework of legal evidence evaluation then arises.