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      Evaluation of the Effects of Mesoglycan on Some Markers of Endothelial Damage and Walking Distance in Diabetic Patients with Peripheral Arterial Disease

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          Abstract

          The aim of this study was to evaluate the variation of some parameters involved in peripheral artery disease progression in diabetic patients with peripheral artery disease after six months of mesoglycan. We enrolled 64 Caucasian, type 2 diabetic patients, with stage IIa peripheral artery disease. They were randomized to mesoglycan (Prisma ®), 50 mg twice a day, or placebo, for six months. We evaluated: glycemic control, metalloproteinase-2, and -9 (MMP-2, and -9), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion protein-1 (sVCAM-1), interleukin-6 (IL-6), soluble E-selectin (sE-selectin), high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), and plasminogen activator inhibitor-1 (PAI-1). We recorded a decrease of MMP-2, MMP-9, sE-selectin, TNF-α, sVCAM-1, and IL-6 compared to baseline, and to placebo in the group treated with mesoglycan. Regarding sICAM-1, and hs-CRP, instead, we recorded a decrease with mesoglycan only compared to baseline. Preliminary results seem to suggest an improvement of pain free walking distance with mesoglycan in 18 patients both compared to baseline and to placebo, even if data should be taken cautiously. Our study showed that supplementation with mesoglycan improved endothelial dysfunction in type 2 diabetic patients with peripheral artery disease. Regarding the preliminary data suggesting also a slight improvement of clinical parameters such as pain free walking distance, more data and a bigger sample of patients are necessary to better verify this aspect.

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          Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: executive summary. The Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD).

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            Society for Vascular Surgery practice guidelines for atherosclerotic occlusive disease of the lower extremities: management of asymptomatic disease and claudication.

            Peripheral arterial disease (PAD) continues to grow in global prevalence and consumes an increasing amount of resources in the United States health care system. Overall rates of intervention for PAD have been rising steadily in recent years. Changing demographics, evolution of technologies, and an expanding database of outcomes studies are primary forces influencing clinical decision making in PAD. The management of PAD is multidisciplinary, involving primary care physicians and vascular specialists with varying expertise in diagnostic and treatment modalities. PAD represents a broad spectrum of disease from asymptomatic through severe limb ischemia. The Society for Vascular Surgery Lower Extremity Practice Guidelines committee reviewed the evidence supporting clinical care in the treatment of asymptomatic PAD and intermittent claudication (IC). The committee made specific practice recommendations using the GRADE (Grades of Recommendation Assessment, Development and Evaluation) system. There are limited Level I data available for many of the critical questions in the field, demonstrating the urgent need for comparative effectiveness research in PAD. Emphasis is placed on risk factor modification, medical therapies, and broader use of exercise programs to improve cardiovascular health and functional performance. Screening for PAD appears of unproven benefit at present. Revascularization for IC is an appropriate therapy for selected patients with disabling symptoms, after a careful risk-benefit analysis. Treatment should be individualized based on comorbid conditions, degree of functional impairment, and anatomic factors. Invasive treatments for IC should provide predictable functional improvements with reasonable durability. A minimum threshold of a >50% likelihood of sustained efficacy for at least 2 years is suggested as a benchmark. Anatomic patency (freedom from restenosis) is considered a prerequisite for sustained efficacy of revascularization in IC. Endovascular approaches are favored for most candidates with aortoiliac disease and for selected patients with femoropopliteal disease in whom anatomic durability is expected to meet this minimum threshold. Conversely, caution is warranted in the use of interventions for IC in anatomic settings where durability is limited (extensive calcification, small-caliber arteries, diffuse infrainguinal disease, poor runoff). Surgical bypass may be a preferred strategy in good-risk patients with these disease patterns or in those with prior endovascular failures. Common femoral artery disease should be treated surgically, and saphenous vein is the preferred conduit for infrainguinal bypass grafting. Patients who undergo invasive treatments for IC should be monitored regularly in a surveillance program to record subjective improvements, assess risk factors, optimize compliance with cardioprotective medications, and monitor hemodynamic and patency status.
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              Progressive vs single-stage treadmill tests for evaluation of claudication.

              The reliability of claudication pain and the metabolic and hemodynamic measurements of the lower limbs of patients with stable peripheral vascular occlusive disease (PVOD) were compared during and following single-stage (S) and progressive (P) treadmill tests. Ten patients (69.8 +/- 1.8 yr; X +/- SE) walked to maximal claudication pain twice a month for 4 months. Patients walked at 1.5 mph up a 7.5% grade (S test) and at 2 mph on a 0% grade, increasing by 2% every 2 min (P test). Distance walked to the onset of claudication pain (CPD) and maximal walking distance (MWD) were recorded. Foot transcutaneous oxygen tension (TcPO2) was measured before, during, and after exercise, while ankle systolic blood pressure (SBP) and the ankle-to-brachial SBP index (ABI) were measured before and after exercise. Intraclass correlation coefficients (R) of CPD and MWD during S tests were R = 0.53 and R = 0.55, respectively. In contrast, the respective R values during P tests were R = 0.89 and R = 0.93. Higher R values of foot TcPO2 were also obtained during and following P tests, while ankle SBP and ABI were highly reliable following both tests. It is concluded that the severity of PVOD is better assessed by P treadmill tests because clinical measurements are more reliable during exercise and recovery.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                06 March 2017
                March 2017
                : 18
                : 3
                : 572
                Affiliations
                [1 ]Centre of Diabetes and Metabolic Diseases, Department of Internal Medicine and Therapeutics, University of Pavia and Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy; labmedmol@ 123456smatteo.pv.it (D.A.); dr.davideromano85@ 123456gmail.com (D.R.); pamelamaffioli@ 123456hotmail.it (M.P.)
                [2 ]Centre for the Study of Endocrine-Metabolic Pathophysiology and Clinical Research, University of Pavia, 27100 Pavia, Italy
                [3 ]Centre for Prevention, Surveillance, Diagnosis and Treatment of Rare Diseases, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
                [4 ]Laboratory of Molecular Medicine, University of Pavia, 27100 Pavia, Italy
                Author notes
                [* ]Correspondence: giuseppe.derosa@ 123456unipv.it ; Tel.: +39-0382-526-217; Fax: +39-0382-526-259
                Article
                ijms-18-00572
                10.3390/ijms18030572
                5372588
                28272312
                9065a623-669b-43f3-82f1-8e678a5d5b32
                © 2017 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 01 November 2016
                : 09 February 2017
                Categories
                Article

                Molecular biology
                endothelial damage,mesoglycan,peripheral artery disease
                Molecular biology
                endothelial damage, mesoglycan, peripheral artery disease

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