119 research outputs found
Inflammation and Microvasculopathy in Renal Ischemia Reperfusion Injury
No full textAcute renal failure (ARF) severely worsens prognosis of hospitalized patients. The most frequent cause of intrarenal ARF is transient or prolonged renal hypoperfusion (ischemia). Ischemia primarily affects the function and structure of tubular epithelial cells, which, in severe cases, is characterized by epithelial cell necrosis. Nevertheless, ischemia does not exclusively lead to alterations of epithelial cells but also causes interstitial inflammation and interstitial microvasculopathy. Both inflammation and microvasculopathy are particularly important in terms of postischemic kidney repair. Postischemic microvasculopathy is characterized by endothelial cell swelling with subsequent microvascular occlusion. Thus, reperfusion is inhibited (no-reflow phenomenon). Such endothelial cell dysfunction offers new therapeutic perspectives in ischemic ARF. Newer observations point towards the role of the so-called endothelial progenitor cells (EPCs) in the treatment of ARF. Systemic administration of EPCs to mice with bilateral renal ischemia mitigates postischemic endothelial cell dysfunction and protects animals from acute renal failure
Gelenkbeteiligung bei Akromegalie
No full textZusammenfassungDie Akromegalie ist eine seltene Erkrankung, welche in den meisten Fällen aus einer hypophysären Überproduktion von Wachstumshormon (GH – Growth Hormone) resultiert. Der in der Folge anhaltende IGF-1(Insulin like Growth Factor-1)-Exzess bewirkt zahlreiche morphologische und metabolische Veränderungen des Organismus inklusive Organomegalie, arterieller Hypertonie und Diabetes mellitus. Insbesondere die kardiovaskuläre Morbidität nimmt zu, diese ist auch hauptverantwortlich für vermehrte Sterblichkeit der Betroffenen. Wiewohl nicht prognoseentscheidend, manifestiert sich die Erkrankung gleichfalls am Bewegungsapparat. Drei Komplikationen sind relevant: eine Arthropathie größerer Gelenke, lumbale Wirbelsäulenveränderungen sowie das Karpaltunnelsyndrom. Die Behandlung dieser Komplikationen unterscheidet sich nicht von der Therapie anderer Krankheitsmanifestationen: entscheidend ist die Beseitigung des GH-/IGF-1-Exzesses. Je früher die Diagnose gestellt und die Behandlung eingeleitet wird, desto besser ist die Prognose, sind doch ossäre/artikuläre Veränderungen in vielen Fällen irreversibel.</jats:p
Akute Nierenschädigung (ANS) – Aktuelles zu (Früh)diagnostik und konservativer Therapie
No full textWas ist neu?
Epidemiologie Die Häufigkeit der akuten Nierenschädigung (ANS) nimmt auf gesamteuropäischer Ebene zu. Dabei lässt sich weltweit keine signifikante Verbesserung der Prognose feststellen.
ANS-Diagnosekriterien und neue Indikatoren der ANS Trotz intensiver Bemühungen konnte bislang kein Marker identifiziert werden, welcher die Serumkreatininkonzentration als ANS-Indikator ersetzen könnte. Mutmaßlich ist eher mit der Etablierung eines diagnostisch-prognostischen Marker-Panels bei ANS zu rechnen.
Konservative Maßnahmen mit gesichertem Nutzen Die derzeit verfügbaren konservativen Therapieempfehlungen sind in den letzten Jahren kaum durch neue Maßnahmen ergänzt worden. Kristalloide Volumenpräparate sind kolloidalen Lösungen meist vorzuziehen. Zudem sind balancierte Elektrolytlösungen Chlorid-reichen Präparationen bei drohender/manifester ANS wahrscheinlich überlegen. Im Rahmen einer jeden Volumentherapie ist eine Hyperhydratation betroffener Patienten jedoch zu vermeiden.</jats:p
Epac-1 activator 8-O-cAMP augments renoprotective effects of allogeneic murine EPCs in acute ischemic kidney injury
No full textPatschan D, Patschan S, Wessels JT, Becker JU, David S, Henze E, Goligorsky MS, Muller GA. Epac-1 activator 8-O-cAMP augments renoprotective effects of allogeneic murine EPCs in acute ischemic kidney injury. Am J Physiol Renal Physiol 298: F78-F85, 2010. First published November 11, 2009; doi:10.1152/ajprenal.00485.2009.-Endothelial progenitor cells (EPCs) protect kidneys from acute ischemic damage. The aim of this study was to identify "treatment parameters" that optimize an EPC-based therapy of acute ischemic renal failure. Male C57BL/6N mice underwent unilateral nephrectomy with simultaneous contralateral renal artery clamping for 30, 35, and 40 min. Tagged murine EPCs were systemically injected at the time of reperfusion. In some experiments, EPCs were pretreated with the Epac (exchange protein directly activated by cAMP-1) activator 8-pCPT-2'-O-Me-cAMP (Epac-1 Ac) and the integrin binding antagonist cyclic Arg-Gly-Asp peptide (cRGD). Injections of 106 EPCs after 30 and 35 min of renal ischemia protected animals from acute renal failure. The same effect occurred with 0.5x10(6) EPCs after a 35-min period of ischemia. If ischemia lasted for 40 min, 0.5x10(6) cells mice did not prevent acute renal failure. To analyze whether EPC integrin receptor activation would modify the cells' renoprotective activity, EPCs were pretreated with Epac-1 Ac. Such animals did not develop acute renal failure, even if ischemia lasted for 40 min. This effect was negated if the cells were pretreated with both Epac-1 Ac and cRGD. In kidneys from those animals medullopapillary EPCs were significantly accumulated. In vitro Epac-1 Ac preactivation of EPCs did not increase the overall expression intensity but induced a redistribution of beta(1)-integrins toward the cell membranes. We conclude that EPC pretreatment with the integrin receptor activator 8-pCPT-2'-O-Me-cAMP augments the anti-ischemic potential of the cells
The hormone melatonin stimulates renoprotective effects of "early outgrowth" endothelial progenitor cells in acute ischemic kidney injury
No full textPatschan D, Hildebrandt A, Rinneburger J, Wessels JT, Patschan S, Becker JU, Henze E, Kruger A, Muller GA. The hormone melatonin stimulates renoprotective effects of "early outgrowth" endothelial progenitor cells in acute ischemic kidney injury. Am J Physiol Renal Physiol 302: F1305-F1312, 2012. First published February 22, 2012; doi:10.1152/ajprenal.00445.2011.-Endothelial progenitor cells (EPCs) protect the kidney from acute ischemic injury. The aim of this study was to analyze whether pretreatment of murine "early outgrowth" EPCs (eEPCs) with the hormone melatonin increases the cells' renoprotective effects in the setting of murine acute ischemic renal failure. Male (8-12 wk old) C57B1/6N mice were subjected to unilateral ischemia-reperfusion injury postuninephrectomy (40 min). Postischemic animals were injected with either 0.5 x 10(6) untreated syngeneic murine eEPCs or with cells, pretreated with melatonin for 1 h. Injections were performed shortly after reperfusion of the kidney. While animals injected with untreated cells developed acute renal failure, eEPC pretreatment with melatonin dramatically improved renoprotective actions of the cells. These effects were completely reversed after cell pretreatment with melatonin and the MT-1/-2 antagonist luzindole. In vitro analysis revealed that melatonin reduced the amount of tumor growth factor-beta-induced eEPC apoptosis/necrosis. Secretion of vascular endothelial growth factor by the cells was markedly stimulated by the hormone. In addition, migratory activity of eEPCs was enhanced by melatonin and supernatant from melatonin-treated eEPCs stimulated migration of cultured mature endothelial cells. In summary, melatonin was identified as a new agonist of eEPCs in acute ischemic kidney injury
Patients with limited and systemic Course of systemic Sclerosis (SS) present a perturbed Regeneration of Endothelial Progenitor Cell System
No full textAcute kidney injury.
No full textAcute kidney injury is a frequent and serious complication in hospitalized patients. Mortality rates have not substantially been decreased during the last 20 years. In most patients AKI results from transient renal hypoperfusion or ischemia. The consequences include tubular cell dysfunction/damage, inflammation of the organ, and post-ischemic microvasculopathy. The two latter events perpetuate kidney damage in AKI. Clinical manifestations result from diminished excretion of water, electrolytes, and endogenous / exogenous waste products. Patients are endangered by cardiovascular complications such as hypertension, heart failure, and arrhythmia. In addition, the whole organism may be affected by systemic toxification (uremia). The diagnostic approach in AKI involves several steps with renal biopsy inevitable in some patients. The current therapy focuses on preventing further kidney damage and on treatment of complications. Different pharmacological strategies have failed to significantly improve prognosis in AKI. If dialysis treatment becomes mandatory, intermittent and continuous renal replacement therapies are equally effective. Thus, new therapies are urgently needed in order to reduce short- and long-term outcome in AKI. In this respect, stem cell-based regimens may offer promising perspectives
Impairment and Differential Expression of PR3 and MPO on Peripheral Myelomonocytic Cells with Endothelial Properties in Granulomatosis with Polyangiitis
No full textBackground. Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are autoimmune-mediated diseases characterized by vasculitic inflammation of respiratory tract and kidneys. Clinical observations indicated a strong association between disease activity and serum levels of certain types of autoantibodies (antineutrophil cytoplasm antibodies with cytoplasmic [cANCA in GPA] or perinuclear [pAN CA in MPA] immunofluorescence). Pathologically, both diseases are characterized by severe microvascular endothelial cell damage. Early endothelial outgrowth cells (eEOCs) have been shown to be critically involved in neovascularization under both physiological and pathological condition. Objectives. The principal aims of our study were (i) to analyze the regenerative activity of the eEOC system and (ii) to determine mPR3 and MPO expression in myelo monocytic cells with endothelial characteristics in GPA and MPA patients. Methods. In 27 GPA and 10 MPA patients, regenerative activity blood-derived eEOCs were analyzed using a culture-forming assay. Flk-1+, CD133+/Flk-1+, mPR3+, and Flk-1+/mPR3+ myelomonocytic cells were quantified by FACS analysis. Serum levels of Angiopoietin-1 and TNF-α were measured by ELISA. Results. We found reduced eEOC regeneration, accompanied by lower serum levels of Angiopoietin-1 in GPA patients as compared to healthy controls. In addition, the total numbers of Flk-1+ myelomonocytic cells in the peripheral circulation were decreased. Membrane PR3 expression was significantly higher in total as well as in Flk-1+ myelomonocytic cells. Expression of MPO was not different between the groups. Conclusions. These data suggest impairment of the eEOC system and a possible role for PR3 in this process in patients suffering from GPA
The endothelial-to-mesenchymal transition and endothelial cilia in EPC-mediated postischemic kidney protection
No full textRenal ischemia induces peritubular capillary rarefication and fibrosis, with the latter partly resulting from the endothelial-to-mesenchymal transition (EndoMT). Endothelial cilia transmit blood flow-associated forces into the cell. Early endothelial progenitor cells (eEPCs) have been shown to protect mice from acute kidney injury in the short term. The aim of the present study was to analyze midterm consequences of eEPC treatment in the context of endothelial cilia and the EndoMT. Male C57/Bl6N mice were subjected to unilateral renal ischemia postuninephrectomy. Syngeneic murine eEPCs were systemically injected at the time of reperfusion. Animals were investigated 1, 4, and 6 wk later. Cultured mature endothelial cells were exposed to a variable flow with versus without eEPC supernatant incubation. Systemically injected eEPCs reduced serum creatinine levels at week 1 (35 and 45 min) and week 4 (45 min). Interstitial fibrosis was significantly diminished by cell treatment at all time points as well. The EndoMT was less pronounced at week 4 (35 min) and week 6 (45 min). eEPC supernatant reduced alpha-smooth muscle actin expression and alpha-tubulin abundance in flow-treated cultured mature endothelial cells, and percentages of cilium-positive cells increased. The loss of peritubular capillaries was prevented by eEPCs. Intrarenal endothelial alpha-tubulin decreased postischemia and was further reduced by eEPC administration. We conclude that eEPCs are capable of reorganizing the endothelial cytoskeleton in an indirect manner, ultimately resulting in stabilization of the endothelial ciliome. The investigation indicates an antimesenchymal role of endothelial cilia in the process of postischemic tissue fibrosis/EndoMT.Deutsche Forschungsgemeinschaft; Jackstadt-Stiftun
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