75 research outputs found

    Pilot study of the safety and efficacy of angiogenic therapy in diabetic foot syndrome

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    BACKGROUND: The syndrome of diabetic foot remains the main cause of non-traumatic amputation of the lower extremity in the world. Even with the provision of comprehensive medical care in the conditions of a specialized center, 10-15% of patients do not succeed in healing the ulcerative defect due to the ischemic component. AIMS: The objective of this study is evaluation of safety and efficacy of pl-VEGF165 transfer in patients with neuroischemic type of diabetic foot syndrome. METHODS: The pilot study included 35 diabetic patients with neuroischemic foot ulcers (Wagner stage 1-2) who were not candidates for revascularization procedures (NCT02538705). The patients were closely monitored after repeated pl-VEGF165 intramuscular gene transfer (2,4 mg) at 1, 3, and 6 months after treatment. The primary efficacy endpoint was the surface area of the ulcers (sq.cm), the secondary endpoints were transcutaneous oxygen tension (Tcp02), ankle-brachial index (ABI), neuropathy disability score (NDS), neuropathy symptoms score (NSS), and Michigan neuropathy screening instrument (MNSI). Adverse events were monitored throughout the study. RESULTS: The use of pl-VEGF165 as part of complex treatment allowed to achieve wound healing in 65,7% of patients with chronic ulcerative defects, the safety of the target limb was 84%. Carrying out therapeutic angiogenesis as a part of the combined therapy ensured a reduction in the average area of the resistant to treatment defects from 3.6 [1.0; 7.05] cm2 to 0.0 [0.0;2.0] cm2 (p=0,001), which correlated with an increase in the TcPo2 index by 15% from 35 [29.5; 40.5] to 40.5 [36.0; 46.5] mm Hg (p= p=0,005) and in the ABI by 16% from 0.96 [0.82;1.08] to 1.11 [0.85; 1.24] (p=0,062). The decrease in the signs of diabetic neuropathy was determined - the scores of NSS scales and VAT decreased from 6,5 [5.75; 8.0) to 6.0 [5.25; 7.0] (p=0,004) and from 9.0 [8.0; 13.5] to 8.0 [7.0; 12.7] (p=0,001), respectively. No adverse effects associated with the use of pl-VEGF165 were recorded. CONCLUSIONS: Thus, preliminary results of the pilot study show that the use of pl-VEGF165 gene transfer in combination therapy allows for complete healing of neuroischemic diabetic foot ulcers in the majority of patients

    Comprehensive assessment of markers of apoptosis and cell proliferation during progression of atherosclerosis after surgery in patients with peripheral arterial disease

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    Abstract Background Determination of predictors that can affect development of atherosclerosis progression in the postoperative period is an urgent problem in vascular surgery. Objectives Integrated assessment of markers of apoptosis and cell proliferation in atherosclerotic lesions and their progression after surgery in patients with peripheral arterial diseases. Methods The investigation included 30 patients with stage IIB-III peripheral arterial disease. All patients have undergone open surgical interventions on the arteries of the aorto-iliac and femoral-popliteal segments. During these interventions, intraoperative specimens were obtained from the vascular wall with atherosclerotic lesions. The following values were evaluated: VEGF А165, PDGF BB, and sFas. Samples of normal vascular wall were obtained from post-mortem donors and used as a control group. Results The levels of Bax and p53 were increased (p&lt;0.001) in samples from arterial wall with atherosclerotic plaque, while sFas values were reduced (p&lt;0.001), compared to their levels in control samples. Values of PDGF BB and VEGF A165 were 1.9 and 1.7 times higher in atherosclerotic lesion samples (p=0.001), in comparison with the control group. The levels of p53 and Bax were increased against a background of reduced sFas levels in samples with progression of atherosclerosis compared to their baseline values in samples with atherosclerotic plaque (p&lt;0.05). Conclusions Initially increased values of the Bax marker against a background of reduced sFas values in vascular wall samples from patients with peripheral arterial disease is associated with risk of atherosclerosis progression in the postoperative period.</jats:p

    New predictors of atherosclerosis progression after surgical interventions on the arteries of the lower extremities

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    BACKGROUNDː Thanks to experiments on animals, the influence of biomarkers of apoptosis, proliferation and endothelial dysfunction on the pathogenesis of atherosclerosis was proved. Aim: to identify the effect of these biomarkers on the progression of atherosclerosis in patients with peripheral arterial disease after surgery. METHODSː Patients were divided into two groups: A - 40 patients who have undergone endovascular interventions, B -38 patients, who have undergone hybrid surgery on the arteries of the lower extremities. Biomarkers Bax, sFas, PDGF BB, and nitric oxide (NO) were studied before intervention, on the 1st, 7th, 30th day after the operation. RESULTSː When comparing initial values of indicators and their values in the dynamics, the difference between group A and B was not found (p &gt; 0.05). Nine patients of group В developed progression of atherosclerosis after 17 months. Roc analysis showed that initial sFas ≤ 0,92 ng / ml, initial Вах ≥ 25,3 ng / ml, NO values ≤128.4 mmol / ml, sFas ≤ 0.645 ng / ml, Вах ≥ 33,8 ng / ml on the first postoperative day, and PDGF BB amount on the 7th day ≥ 28 ng / ml is associated with progression of atherosclerosis. CONCLUSIONSː The dynamics of biomarkers of apoptosis, proliferation and endothelium dysfunction in patients after endovascular and hybrid interventions did not differ significantly. The activation of two pathways markers of apoptosis against the background of reduced synthesis of NO leads to an enhanced proliferative response and is associated with progression of atherosclerosis after surgery

    Clinical effectiveness of bioflavonoids in the treatment of secondary lower limb lymphedema

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    AIM: This study aimed to investigate the effectiveness of the application of a combination of the preparation of micronized purified flavonoid fraction (MPFF) and elastic compression in patients with acquired lymphostasis.&#x0D; MATERIALS AND METHODS: Sixty patients with stage II secondary lower limb lymphedema according to М. Foeldi were included. The patients were divided into two groups through randomization with the envelope method. The first group (n = 30) was subjected to a conservative treatment (MPFF, 1000 mg/day) coupled with elastic compression (3rd class compression stockings). The second group was given compressive therapy (third-class compression stockings). The patients were physically examined through the measurement of the circumference of the limb at different levels.&#x0D; RESULTS: In the first group, the circumference of the lower third of the shin decreased by 8.15% (p = 0.005) after 1 month and by the end of treatment by 10.6% (p 0.001), of the middle third of shin by 3.15% (p = 0.001) and 4.78% (p 0.001), and of the upper thirdby 4.08% (p 0.001) and 5.99% (p 0.001). By the end of the observation period (3 months), the circumference of the lower third of the shin in the second group (29.68 4.67 cm) was significantly greater than that in the first group (26.65 2.92 cm, p = 0.035). No adverse reactions were observed in the MPFF group.&#x0D; CONCLUSIONS: The volume of the lower limbs of patients with acquired lymphedema decreased after using a combination of MPFF and elastic compression to a larger extent than after the isolated use of elastic compression. Patients taking MPFF had a positive clinical effect without adverse reactions. Therefore, MPFF could be used in the pharmacotherapy of secondary lymphedema of the lower limbs.</jats:p
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