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Critical limb ischemia and autologous cell therapy in diabetic foot disease, pathogenesis of Charcot osteoarthopathy.
Němcová, Andrea ; Jirkovská, Alexandra (advisor) ; Polák, Jan (referee) ; Prázný, Martin (referee)
Diabetic foot disease (DFD) is a serious complication of diabetes and, along with critical limb ischemia, significantly exacerbates the prognosis of patients. Peripheral arterial disease in patients with diabetes has an atypical clinical course, its diagnosis is challenging and is one of the most common causes of morbidity and mortality of patients with DFD. The aim of this dissertation focused on the diagnosis and treatment of DFD was to identify a suitable method for evaluating the effect of autologous cell therapy (ACT), to assess options for early diagnosis of Charcot osteoarthropathy (COA) and, possibly, to establish the association between the incidence of cardiovascular disease and DFD. In our studies concerning therapeutic vasculogenesis, we observed a significant increase in the antiangiogenic factor endostatin after ACT in contrast to its unchanged levels after standard percutaneous transluminal angioplasty; the transient increase in endostatin seems to be a marker of therapeutic vasculogenesis after ACT. A benefit of using calf muscle perfusion scintigraphy in the assessment of microcirculation and ACT effect was not clearly demonstrated. By contrast, a promising method for the evaluation of microcirculation and the effect of revascularization after ACT was MR spectroscopy of calf...
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Local and systemic pathological processes in diabetic foot diasease and their management
Dubský, Michal ; Jirkovská, Alexandra (advisor) ; Rušavý, Zdeněk (referee) ; Karetová, Debora (referee)
Local tissue factors, ischemia and infection (which are often the cause of re-ulceration) are the main pathogenetic factors for diabetic foot disease (DFD). Neuropathic bone metabolism disorder leads to Charcot osteoarthropathy (CHOA). The aim of this dissertation was to assess experimentally the effectiveness of new skin substitutes, evaluate local vasculogenesis in different types of cell therapy of DFD, the role of infection in recurrence of DFD and scintigraphic parameters of activity of CHOA. Our studies concerning local pathological processes in DFD experimentally proved that gelatine nanofibers accelerate wound healing and can be suitable scaffolds for cell transfer and skin regeneration and also that acellular porcine dermis is more effective in healing of chronic wounds then xenotransplants. Our studies concerning therapeutic vasculogenesis confirmed that efficacy of stem cells (SC) harvested from bone marrow is similar in efficacy to SC separated from peripheral blood after stimulation. We found no evidence for systemic vasculogenesis by means of a significant increase of pro-angiogenic cytokines, which confirms the paracrine effect of injected SC. We proved a significant correlation between angiogeneisis inhibitor (endostatin) and the number of injected SC, which could be an indicator of...
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