glucuronyl-glucosamine-glycan-sulfate and Varicose-Veins

Inflammation represents an important epiphenomenon in the etiopathogenesis of chronic venous disease, a worldwide debilitating condition affecting millions of subjects. The pathophysiology of chronic venous disease (CVD) is based on the hemodynamic abnormalities in conjunction to alterations in cellular and extracellular matrix biocompounds. The endothelial dysfunction results from early perturbation in the endothelium linked to glycocalyx injury and promoted by inflammatory cells and mediators (such as matrix metalloproteinases and interleukins), which lead to progressive dilation of the vein resulting in chronic venous insufficiency. Activated leukocytes during the inflammatory process release enzymes, free radicals, chemokines and inflammatory cytokines in the vessel microenvironment, which are responsible for the changes of the venous wall and venous valve, reflux and venous hypertension, and the development/progression of tissue destruction and skin changes. Sulodexide, a highly purified mixture of glycosaminoglycans composed by 80% fast moving heparin and 20% of dermatan sulphate, exhibits anti-thrombotic and profibrinolytic properties, restoring also the essential endothelial glycocalyx. Glycosaminoglycan sulodexide has been also characterized to reduce the release of inflammatory cytokines/chemokines and to inhibit the matrix metalloproteinases-related proteolytic cascades, counteracting endothelial dysfunctions. The pleiotropic effects of sulodexide set the basis for a very promising agent in treating the spectrum of CVD.

Topics: Animals; Anti-Inflammatory Agents; Cardiovascular Agents; Chronic Disease; Cytokines; Glycosaminoglycans; Humans; Inflammation Mediators; Signal Transduction; Treatment Outcome; Varicose Veins; Veins; Venous Insufficiency

Sclerotherapy for the treatment of varicose veins is one of the most common medical procedures performed in the Western world, and hyperpigmentation is one of the most frequent, dreaded, minor adverse events. There has recently been some interest in investigating the inflammatory response of the local endothelium after sclerotherapy and the possible benefits of venoactive drugs because of their pleiotropic properties. The aim of this study was to evaluate whether adding a venoactive drug (sulodexide) to the standard sclerotherapy treatment protocol for patients with varicose veins can reduce the occurrence of postsclerotherapy hyperpigmentation.. We carried out a prospective, multicenter, randomized controlled trial with a parallel group design. It included 720 patients with telangiectasia, reticular veins, or varicose veins who were candidates for sclerotherapy. Patients with reflux in deep system or saphenous veins were excluded. Group A consisted of 354 patients who received an oral dose of sulodexide twice a day for 7 days before scheduled sclerotherapy; the treatment then continued for 3 months. Group B consisted of 366 patients who received the standard sclerotherapy protocol. Polidocanol was used as the sclerosing agent, and 20 to 30 mm Hg compression stockings were used in both groups for 7 days. Control photographs were taken, and a follow-up examination took place after 1 month and 3 months. Computer software was used to analyze the treated area for incidence of hyperpigmentation, total area of hyperpigmentation, skin tone increase in the hyperpigmented area, vein disappearance, and incidence of major bleeding. The sample size was calculated to give a statistical power of 80%. Student t-test and the χ. A total of 609 patients completed the 3-month follow-up: 312 in group A and 297 in group B. After 1 month, the incidence of hyperpigmentation was 8.7% in group A and 14.8% in group B (P = .01). Group A developed an average area of hyperpigmentation of 10.7% compared with 18.2% in group B (P = .01), and the skin tone of the hyperpigmented area was lower in group A than in group B (P = .02). However, the latter difference was not significant after 3 months. The overall vein disappearance rate was similar in both groups.. Our analysis shows that by adding a venoactive drug (sulodexide) to the standard sclerotherapy protocol, the occurrence of hyperpigmentation is reduced without affecting the desired therapeutic vein elimination response.

Topics: Adult; Female; Glycosaminoglycans; Humans; Hyperpigmentation; Male; Mexico; Middle Aged; Polidocanol; Prospective Studies; Sclerosing Solutions; Sclerotherapy; Skin Pigmentation; Telangiectasis; Time Factors; Treatment Outcome; Varicose Veins

High pressure in the lower-limb veins is often associated with chronic venous insufficiency and varicose veins (VVs), making it important to search for the mechanisms and agents that control venous function. We have shown that protracted increases in venous stretch/wall tension reduce vein contraction and augment matrix metalloproteinase (MMP)-2 and -9. Also, MMP-2 and MMP-9 promote venodilation, a hallmark of VVs. Sulodexide (SDX) is a blend of glycosaminoglycans with efficient profibrinolysis and antithrombosis activities, but its actions on vein function and the mechanisms involved are unclear. We tested the hypothesis that SDX enhances venous contractile response by decreasing MMP expression/activity in veins subjected to protracted stretch. Rat inferior vena cava (IVC) rings were treated with SDX (0.001-1 mg/mL) or vehicle, equilibrated under control 0.5-g resting tension or protracted 2-g stretch for 18 hours, and the contractile response to 96-mM KCl and phenylephrine (Phe) in SDX-treated and nontreated veins was recorded. In IVC rings under control 0.5-g resting tension, SDX caused dose-dependent contraction, 96-mM KCl caused marked contraction (176-mg/mg tissue), and Phe caused dose-dependent contraction with a maximum (56-mg/mg tissue) at 10 M. In IVC subjected to protracted 2-g stretch, 96-mM KCl-induced contraction was reduced to 112 mg/mg and maximal Phe-induced contraction was decreased to 23 mg/mg. In IVC subjected to protracted 2-g stretch plus SDX, 96-mM KCl-induced contraction was restored to 228 mg/mg and maximal Phe-induced contraction was improved to 115 mg/mg. Gelatin zymography and Western blots revealed increases in MMP-2 and MMP-9 levels/gelatinolytic activity in veins subjected to protracted 2-g stretch and reversal to control levels in veins subjected to 2-g stretch plus SDX. Thus, SDX improves vein function and augments the contractile response in veins subjected to protracted stretch. The SDX-induced improvement of contraction and restoration of vein function appear to involve decreases in MMP-2 and MMP-9 and may contribute to the benefits of SDX in chronic venous insufficiency and VVs.

Topics: Animals; Down-Regulation; Glycosaminoglycans; In Vitro Techniques; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Proteolysis; Rats, Sprague-Dawley; Varicose Veins; Vasoconstriction; Vasoconstrictor Agents; Vena Cava, Inferior; Venous Insufficiency

Foam sclerotherapy is a clinical procedure for the treatment of unhealthy veins. The aim of this study was to investigate the effect of sulodexide (SUL) on stability of foams prepared using polidocanol (POL) and sodium tetradecyl sulfate (STS) detergents, more specifically with 0.25% aethoxysclerol and 0.2% Fibro-Vein sclerosing solutions.. Foams were produced by the Tessari method using three different weight ratios of POL-SUL and STS-SUL (1:0, 1:1, and 1:3).. The half-life of STS foams resulted as follows: 82 ± 1.6 s, 101.8 ± 2.6 s, and 109.7 ± 2.1 s for 1:0, 1:1, and 1:3 STS-SUL weight ratios, respectively. The same ratios were used for POL foams with the following results: 90.6 ± 3 s, 106.8 ± 2.6 s, and 107.6 ± 2.7 s for 1:0, 1:1, and 1:3 POL-SUL weight ratios, respectively.. The addition of SUL in sclerosing solutions can prolong the half-life of foams, and it could be potentially used as a foam stabilizer.

Topics: Glycosaminoglycans; Humans; Sclerosing Solutions; Sclerotherapy; Varicose Veins

The aim of this paper was to assess the use of venoactive drugs (VADs) after surgery for chronic venous disease in our operative unit in terms of patients' compliance to the therapy and a possible effect on the postoperative pain and quality of life (QoL).. Data of consecutive patients who underwent surgery were retrospectively analyzed. All patients, through telephone interview 90 days after the operation, were asked about taking the VAD (either sulodexide or MPFF) which was recommended during the postoperative period. Data were collected about the duration of therapy, the intensity of perceived pain (0-10 scale) at 1st, 7th and 30th postoperative days (POD), the length of rest from their daily activities and QoL during the first postoperative month (through Italian SF-12 questionnaire). P values <0.05 were considered significant. Results of patients who took the VAD were compared to those of patients who did not take the VAD (case-controlled study).. A total of 132 patients were operated on (43 with endovenous radiofrequency ablation, RFA; 43 with stripping or crossectomy; 46 with phlebectomies). The proportion of patients who took VADs was two thirds, similar among the three groups. Of those, 24% took VADs for less than 30 days. No significant differences were recorded between those who took and those who didn't take any drugs in terms of intensity of pain at 1st, 7th and 30th POD, days of rest from daily activities and QoL.. Irrespectively of the groups, about one third of the patients did not take the recommended VAD postoperatively. No significant difference was recorded between those who took the therapy and those who did not in terms of intensity of postoperative pain, length of rest from daily activities and QoL.

Topics: Case-Control Studies; Catheter Ablation; Female; Glycosaminoglycans; Humans; Male; Middle Aged; Pain Measurement; Pain, Postoperative; Quality of Life; Recurrence; Saphenous Vein; Surveys and Questionnaires; Varicose Veins

Chronic venous disease (CVeD) is a debilitating condition that affects millions of individuals worldwide. The condition can result in varicose veins, or advance to severe skin changes and venous ulceration. The fundamental basis for CVeD is inflammation within the venous circulation and that it is subjected to increased hydrostatic pressure resulting in increased ambulatory venous pressure. The inflammation involves leukocytes, in particular macrophages and monocytes, inflammatory modulators and chemokines, cytokine expression, growth factors, metalloproteinase (MMP) activity, and many regulatory pathways that perpetuate inflammation. Sulodexide (SDX) is a glycosaminoglycan with pro-fibrinolytic and anti-thrombotic properties. We have previously demonstrated that SDX inhibits the secretion of pro-zymogen MMP-9 from human leukocytes without displacing high molecular complexes of MMP-9. The anti-inflammatory properties of SDX on activated leukocytes have not been well established. We hypothesized that SDX will reduce the secretion of inflammatory mediators from lipopolysaccharide (LPS)-stimulated macrophages. Therefore, we evaluated the effects of SDX on LPS-stimulated macrophage secretion of various inflammatory and anti-inflammatory cytokines, chemokines, and colony stimulating factors. We used microplatebased multiplex immunoassays. LPS-stimulated macrophages in vitro caused a substantial increase of interleukins, tumor necrosis factor, interferon, chemokines and colony stimulating factors. The addition of SDX caused both a dose-dependent and dose-independent decrease in nearly all of the inflammatory cytokines, chemokines and colony stimulating factors. These findings suggest that SDX has a significant effect on the release of inflammatory mediators from macrophages, and may be useful in the treatment of early and advanced CVeD.

Topics: Anti-Inflammatory Agents; Chemokines; Chronic Disease; Colony-Stimulating Factors; Cytokines; Dose-Response Relationship, Drug; Down-Regulation; Glycosaminoglycans; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Lipopolysaccharides; Macrophages; U937 Cells; Varicose Veins

Topics: Cardiovascular Agents; Chronic Disease; Glycosaminoglycans; Humans; Treatment Outcome; Varicose Veins; Venous Insufficiency