glucuronyl-glucosamine-glycan-sulfate and Chronic-Disease

Chronic venous disease (CVD) is a common condition associated with valvular dysfunction, venous hypertension and endothelial inflammation. Sulodexide facilitates the healing of venous ulcers and is frequently used in patients with CVD without ulcer. This review assessed the efficacy and safety of sulodexide for treatment of signs and symptoms of lower extremity CVD.. We searched MEDLINE, EMBASE, CINAHL and AMED as well as the Cochrane Central Register of Controlled Trials and the World Health Organisation (WHO) International Clinical Trials Registry Platform Search Portal. We also manually searched potentially relevant journals, conference proceedings and journal supplements. Any study monitoring any effect of sulodexide in patients with CVD at any stage of the disease, classified or non-classified, was considered. Treatment effects were estimated using standardised mean differences (SMDs), mean differences (MDs) and risk ratios (RRs), as appropriate. We calculated 95% confidence intervals (CIs) and heterogeneity (Q, tau and I. The search found 64 studies, but only 23 provided data on 7153 participants (mean age 55 years; 68% female). The 13 studies providing extractable quantitative information included 1901 participants (mean age 55.2 years; 65% female). Sulodexide decreased the intensity of pain, cramps, heaviness, oedema and total symptom score and reduced inflammatory mediators in patients with CVD. The risk of adverse events (AEs) was not different between sulodexide and placebo or heparan sulphate (RR 1.31, 95% CI 0.74-2.32; I. Sulodexide was found to have a beneficial venoactive effect on the major signs and symptoms of CVD such as pain, cramps, heaviness and oedema without increasing the risk of AEs. It is also likely to exert a systemic effect on the course of CVD by interfering with inflammatory chemokines.

Topics: Adult; Anticoagulants; Chronic Disease; Female; Glycosaminoglycans; Humans; Inflammation Mediators; Lower Extremity; Male; Middle Aged; Pain Measurement; Venous Insufficiency

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

Chronic venous disease encompasses a range of venous disorders, including those involving the lower limbs resulting from venous hypertension. The spectrum of chronic venous disease signs and symptoms shows variable severity, ranging from mild (aching, pain, and varicose veins) to severe (venous ulcers). The pathophysiology of chronic venous disease is characterized by venous hypertension, which triggers endothelial dysfunction and inflammation leading to microcirculatory and tissue damage, and eventually to varicose veins and venous ulcers. Sulodexide is an orally active mixture of glycosaminoglycan (GAG) polysaccharides with established antithrombotic and profibrinolytic activity. The agent is used in the treatment of a number of vascular disorders with increased risk of thrombosis, including intermittent claudication, peripheral arterial occlusive disease and post-myocardial infarction. Sulodexide differs from heparin because it is orally bioavailable and has a longer half-life and a smaller effect on systemic clotting and bleeding. An increasing body of preclinical evidence shows that sulodexide also exerts anti-inflammatory, endothelial-protective, and pleiotropic effects, supporting its potential efficacy in the treatment of chronic venous disease. Clinical studies of sulodexide have shown that the agent is associated with significant improvements in the clinical signs and symptoms of venous ulcers, and is therefore a recommended therapy in combination with local wound care and bandages for patients with persistent venous leg ulcers. Preliminary evidence supports the use of sulodexide in the prevention of recurrent deep venous thrombosis. Sulodexide was generally safe and well tolerated in clinical trials, without hemorrhagic complications. Sulodexide therefore appears to be a favorable option for the treatment of all stages of chronic venous disease and for the prevention of disease progression.

Topics: Animals; Chronic Disease; Clinical Trials as Topic; Disease Progression; Fibrinolytic Agents; Glycosaminoglycans; Humans; Varicose Ulcer; Vascular Diseases

Chronic kidney failure remains a major health problem worldwide. Although current treatment is focused on the renin-angiotensin system, it is essential that new treatments targeted toward novel pathophysiological mechanisms are developed if we are to make significant progress in this area. In this review, we have outlined several promising new areas while emphasizing that large, randomized, well-controlled clinical trials are essential to reach a meaningful conclusion about the efficacy and safety of novel treatment.

Topics: Amides; Anticoagulants; Antihypertensive Agents; Bicarbonates; Chronic Disease; Enzyme Inhibitors; Fumarates; Glycosaminoglycans; Humans; Indoles; Iron Chelating Agents; Kidney Diseases; Kidney Failure, Chronic; Maleimides; Pentoxifylline; Phosphodiesterase Inhibitors; Protein Kinase C; Pyridones; Renin; Renin-Angiotensin System

The authors studied efficacy of using sulodexide (Vessel Due F) in treatment of patients with clinical class C6 chronic venous disease (CVD) and type 2 diabetes mellitus (DM). The study included a total of sixty-two 18-to-75-year-old patients of both sexes suffering from class C6 CVD and type 2 DM. The patients were randomly assigned to either the Study Group (Group I) and Control Group (Group II) in the ratio of 1:1. The Study Group patients received treatment with sulodexide according to the standard regimen during 50 days. The study included taking case history, examination by a phlebologist and endocrinologist, measuring the malleolar volume, body weight, ultrasound examination of lower-limb vessels, clinical and biochemical blood analyses, coagulogram, planimetry of trophic ulcers, microbiological and cytological study. The primary end point was epithelialization of trophic ulcers after 1 month. Secondary endpoints were ulcer healing after 2 months and dynamic alterations during epithelialization. The Study Group patients as compared to the Control Group patients were found to have statistically significant improvement of the composite index of clinical assessment of VSCC severity, decrease in the malleolar volume, positive dynamics of speed velocity parameters of venous outflow and improvement of quality of life according to the SF-36 questionnaire. After 30 days, epithelialization was achieved in 11 (33.5%) cases in the Study Group and in 6 (19.4%) cases in the Control Group (p<0.05). After 60 days, epithelialization was achieved in 27 (87.1%) and 15 (48.4%) patients of the Study and Control Groups, respectively. The time to complete epithelialization in Group I and II patients amounted to 49.8 ± 1.4 and 76.6 ± 2.4 days, respectively (p<0.05). A conclusion was drawn that administration of sulodexide (Vessel Due F) is effective and pathogenetically substantiated in treatment of patients presenting with class C6 CVD and type 2 DM.. Изучена эффективность применения препарата сулодексид (Вессел Дуэ Ф) при лечении пациентов с хроническими заболеваниями вен (ХЗВ) С6 клинического класса и сахарным диабетом (СД) 2 типа. В исследование включены 62 пациента обоего пола в возрасте от 18 до 75 лет с ХЗВ С6 класса и СД 2 типа. Больные рандомизированы в основную (І) и контрольную (ІІ) группы в соотношении 1:1. Пациенты основной группы получали лечение препаратом сулодексид по стандартной схеме в течение 50 дней. При исследовании производили: сбор анамнеза, осмотр флеболога и эндокринолога, измерение маллеолярного объема, массы тела, ультразвуковое исследование сосудов нижних конечностей, клинический и биохимический анализы крови, коагулограмму, планиметрию трофических язв, микробиологическое и цитологическое исследование. Первичная конечная точка исследования – эпителизация трофических язв через 1 месяц. Вторичные конечные точки – заживление язв через 2 месяца и динамические изменения в процессе эпителизации. В основной группе по сравнению с контрольной выявлены статистически значимое улучшение суммарного показателя по клинической оценке тяжести заболевания VSCC, уменьшение маллеолярного объема, положительная динамика скоростных показателей венозного оттока и улучшение показателей качества жизни по опроснику SF-36. Через 30 дней эпителизация достигнута в 11 (33,5%) наблюдениях в основной и в 6 (19,4%) наблюдениях в контрольной группе (р<0,05). Через 60 дней эпителизация достигнута у 27 (87,1%) и 15 (48,4%) больных в основной и контрольной группах соответственно. Время полной эпителизации у пациентов І и ІІ групп соответственно составило 49,8±1,4 и 76,6±2,4 суток (р<0,05). Сделан вывод, что применение сулодексида (Вессел Дуэ Ф) является эффективным и патогенетически обоснованным при лечении пациентов с ХЗВ С6 класса и СД 2 типа.

Topics: Adult; Aged; Chronic Disease; Cytoprotection; Diabetes Mellitus, Type 2; Drug Monitoring; Endothelium, Vascular; Female; Fibrinolytic Agents; Glycosaminoglycans; Humans; Hypoglycemic Agents; Lower Extremity; Male; Middle Aged; Severity of Illness Index; Treatment Outcome; Ultrasonography, Doppler, Duplex; Vascular Diseases

Urinary albumin excretion frequently persists in diabetic patients who are treated with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB). Sulodexide, a glycosaminoglycan mixture of 80% heparan sulfate and 20% dermatan sulfate, has been hypothesized to reduce persistent albuminuria. We have conducted a multi-center randomized double-blind pilot study in order to determine the effect of 6 months' therapy with sulodexide on urinary albumin excretion and to address logistical issues for a full-scale trial.. A total of 149 patients with type 2 diabetes and an albumin:creatinine ratio (ACR) between 20 and 300 mg/g were randomized with equal allocation to either placebo, 200 mg of sulodexide or 400 mg of sulodexide. The primary endpoint was the achievement, at 6 months, of either 3(1) return to normoalbuminuria (ACR < 20 mg/g with a decrease of at least 25%) or (2) a decrease in ACR of at least 50% from the baseline value. All patients used a maximum tolerated recommended FDA approved dose of an ACEI or ARB for at least 60 days and had stable blood pressure prior to randomization.. The primary efficacy endpoint was achieved in 25.3% of the patients in the two sulodexide groups combined versus 15.4% of the placebo-treated patients (P = 0.26). The primary endpoint was achieved in 33.3% (P = 0.075 for the comparison to placebo) in the sulodexide 200 mg group and 18.4% (P = 0.781) in the sulodexide 400 mg group. (No consistent patterns of side effects were observed.. Based on the experience gained in this pilot study, one full-scale trial is currently being conducted to evaluate the effects of sulodexide on change in ACR in patients with persistent microalbuminuria, and a longer-term trial is underway to evaluate the effects of sulodexide on long-term renal disease progression in patients with overt proteinuria.

Topics: Aged; Albuminuria; Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Confidence Intervals; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Glycosaminoglycans; Humans; Hypoglycemic Agents; Male; Middle Aged; Pilot Projects; Probability; Reference Values; Severity of Illness Index; Treatment Outcome; Urinalysis

A novel pathogenetic approach to treatment of diabetic nephropathy (DN) as a severe complication of diabetes mellitus is aimed at inhibiting DN progression or its involution by means of reestablishment of heparan sulfate synthesis by glycosaminoglycane drug. In the study of 9 patients with microalbuminuria and 9 with proteinuria this drug was low-molecular heparin-sulodexide (Alfa-Wasserman, Italy). The treatment course of 3 weeks resulted in albuminuria fall in 89% of patients. In patients with microalbuminuria protein excretion returned to normal values in a week of treatment. This effect was persistent after the drug discontinuation. This was not so for protein excretion in proteinuria patients which became low after 3 weeks of treatment, but the effect was not long-lasting. The authors believe that glycosaminoglycanes hold great promise in DN, especially at early stages of renal diabetic affection.

Topics: Adolescent; Adult; Albuminuria; Chronic Disease; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Glycosaminoglycans; Heparin, Low-Molecular-Weight; Humans; Hypoglycemic Agents; Middle Aged; Time Factors

A double-blind, placebo-controlled study was carried out in 36 patients, aged 30 to 50 years, to evaluate the effectiveness of oral sulodexide in the treatment of chronic venous insufficiency due to idiopathic varices. Patients were allocated at random to receive either oral sulodexide as 2 capsules (each containing 250 lipoproteinolipase releasing units) twice daily or 2 identical placebo capsules twice daily over a period of 45 days. Using strain gauge plethysmographic data, assessments were made of the microcirculatory effects of treatment by calculating the coefficient of capillary filtration from measurements made on both legs of each patient on entry and after 30 and 45 days of treatment. The coefficient is derived from the transmembranous flow values at the occlusive pressures of 60 and 40 mmHg, the difference between the two occlusive pressures examined and a corrective factor to calculate the capillary pressure based on the pressure in the venous circulation. Statistical analysis of the results showed that sulodexide produced a significant mean reduction from baseline values of the coefficient at both the 30 and 45 day examinations whereas the coefficient increased in the placebo group. The difference between the two groups was also statistically significant. These findings suggest that sulodexide has a positive influence on capillary permeability.

Topics: Administration, Oral; Adult; Chronic Disease; Double-Blind Method; Female; Glycosaminoglycans; Humans; Hypolipidemic Agents; Male; Middle Aged; Plethysmography; Venous Insufficiency

Topics: Chronic Disease; Glycosaminoglycans; Humans; Vascular Diseases

Topics: Adult; Aged; Aged, 80 and over; Cell Line; Chronic Disease; Endoglin; Female; Glycosaminoglycans; Humans; Male; Middle Aged; Protein Isoforms; Transforming Growth Factor beta; Varicose Ulcer; Venous Insufficiency; Wound Healing

Sulodexide is a glycosaminoglycan approved for the treatment of chronic venous disease (CVD). It has been available in Mexico since 2012. The aim of the study was to understand the clinical experience of primary care physicians in the treatment of CVD with sulodexide.. Clinical data collection forms were distributed among general practitioners. Data was collected for up to four follow-up consultations. All signs and symptoms were rated with the Likert Scale at each examination: 0 to 5 (where 0 means none, and 5 very severe). Both the patient's and the physician's opinions of the effects of the treatment were recorded.. Data were collected from 1599 patients at different clinical stages of CVD, 52% of which were at advanced stages (C4-C6). A total of 434 cases were followed up with four examinations (median of thirty days between each examination). In these cases, the overall sign and symptom score decreased significantly at each examination (P<0.01). At the fourth examination, 98.9% of the patients felt better or much better than at the first examination, and 99.7% were better or much better in the physician's opinion (P<0.01). The only adverse effect was nausea, reported in two cases.. Sulodexide was effective and well tolerated in the treatment of CVD.

Topics: Adolescent; Adult; Aged; Chronic Disease; Female; Glycosaminoglycans; Humans; Male; Mexico; Middle Aged; Nausea; Practice Patterns, Physicians'; Primary Health Care; Severity of Illness Index; Surveys and Questionnaires; Venous Insufficiency; Young Adult

According to previous studies, sulodexide suppresses intravascular inflammation when used in patients with chronic venous disease (CVD). In the current study, we tested the effect of prolonged in vitro exposure of human venous endothelial cells to the serum from patients with CVD, examining the function of these cells and how it is modified when these cells are simultaneously exposed to sulodexide.. Human umbilical venous cells (HUVEC) were cultured in standard medium (control), in medium supplemented with 5% serum pooled from CVD patients (CVD-serum) or in medium from CVD patients who were treated with sulodexide (CVD-serum-SUL). The synthesis of interleukin-6 (IL-6), monocyte chemoattractant protein -1(MCP-1) and soluble intercellular adhesion molecule - 1 (s-ICAM-1) were studied at the beginning of incubation and were measured after 9 and 15 days of exposure to the studied media. The concentration of IL-6 after cell stimulation by interleukin -1 (IL-1) was also measured. In a subsequent part of the experiment, the effect of the studied sera on the in vitro replicative ageing of HUVEC was evaluated. A total of 15 passages of the cell culture were performed and both the PDT (population doubling time) and the cell hypertrophy were assessed.. The concentrations of Il-6, MCP-1, and ICAM-1 gradually increased in the supernatants containing 5% CVD serum compared with the control medium. In the supernatants obtained after cell incubation with serum from sulodexide treated patients, the increase in concentrations of IL-6, MCP-1 and ICAM-1 was significantly less than the control. Release of IL-6 after stimulation with IL-1 (100 pg/mL) was the highest in the CVD-serum group: 3540±670 pg/105 cells vs. 1850±540 pg/105 cells in the control (P<0.01 vs. CVD-serum) and 2320 ±430 pg/105 cells in CVD-serum-SUL (P<0.02 vs. CVD-serum). PDT was significantly longer in the cells incubated with CVD serum compared with the control group, and PDT was reduced when serum from sulodexide treated patients was used. The cells became senescent in the presence of CVD serum, but the cells obtained from patients at the end of 8 weeks of treatment with sulodexide showed a much weaker inflammatory phenotype than the CVD group.. Chronic in vitro exposure of HUVEC to medium supplemented with CVD patient serum induces an inflammatory phenotype. Sulodexide treatment significantly reduces that effect and slows HUVEC senescence in the milieu of CVD serum.

Topics: Aged; Cells, Cultured; Chemokine CCL2; Chronic Disease; Endothelial Cells; Glycosaminoglycans; Humans; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-6; Middle Aged; Vascular Diseases

Chronic venous disease (CVD) of the lower limbs is a common problem. It is more prevalent in women than in men and has a significant impact on patients' quality of life (QoL) and on the healthcare system. The aim of this study was to evaluate the efficacy of sulodexide in adult patients with CVD of the lower limbs and its effect on patients' QoL.. Patients with CVD were treated with sulodexide [250 LSU (lipasemic units) twice daily] for 3 months in a setting of real-life clinical practice. The endpoints of this observational non-comparative, open-label prospective study were the clinical efficacy of sulodexide (evaluated by scoring objective and subjective symptoms with a Likert-type scale) and the impact of sulodexide therapy on patients' QoL [assessed using the chronic venous insufficiency quality of life questionnaire (CIVIQ)].. The study included 450 patients (mean age 46.9 ± 10.5 years, range 17-78 years). A greater percentage of patients were female (65.4%). Three months of treatment with sulodexide significantly improved all objective and subjective symptoms (p < 0.0001). Overall, patients reported a significant improvement in all QoL scores (p < 0.0001). Adverse events were spontaneously reported by two patients (one case of epigastric pain and one of gastric pain with vomiting).. Oral sulodexide significantly improves both objective and subjective symptoms, as well as functional and psychological aspects of QoL in patients with CVD.. No funding or sponsorship was received for this study. Sponsorship for article processing charges and open access fees was provided by Alfa Wassermann.

Topics: Adult; Anticoagulants; Chronic Disease; Female; Glycosaminoglycans; Humans; Lower Extremity; Male; Middle Aged; Prospective Studies; Quality of Life; Surveys and Questionnaires; Treatment Outcome; Tunisia; Venous Insufficiency

According to previously performed studies, inflammation plays a crucial role in vein wall and leg tissue injury related to chronic venous insufficiency (CVI) development. Sulodexide (SUL) is a balanced mix of glycosaminoglycans with potential anticoagulant and profibrinolytic activity, also protecting endothelial cells and suppressing inflammatory reactions in various vascular disease-related conditions. The goal of the present study was to evaluate the anti-inflammatory action of SUL in patients with CVI.. The study was performed on a group of 11 patients with chronic venous disease (stage C5 according to CEAP classification). The mean age of the patients was 58.4±7.7 years, and none of them were diabetic. The patients were treated for 8 weeks with orally-administered SUL (2 x 500 LSU/day). Blood samples were collected at the start and at the end of the study for measurement of MMP-9, IL-6 and monocyte chemoattractant protein-1 (MCP-1). Additionally, the effect of the obtained serum samples on the function of human venous endothelial cells (HVEC) in in-vitro culture was evaluated.. After treatment with SUL, the serum concentration of MMP-9 (ng/mL) decreased from 6.50±3.48 to 5.41±1.36, P<0.05, and the concentration of IL-6 (pg/mL) decreased from 11.5±3.4 to 10.1±2.3, P<0.005. There was also a trend of decreased serum MCP-1 (pg/mL) from 31.3±23.0 before treatment to 27.1±10.7 at the end. Intracellular generation of oxygen-derived free radicals in HVEC maintained in in-vitro culture was lower in the serum samples collected after treatment with SUL: 3.09±0.35 abs/μg protein vs. 3.63±0.32 abs/μg protein, at the start, P<0.05. Synthesis of IL-6 was lower in HVEC exposed in vitro to serum collected at the end of SUL treatment: 1.02±0.31 ng/μg cell protein vs. 1.32±0.41 ng/μg cell protein before SUL treatment. The proliferation rate of HVEC was similar in serum collected at the beginning and at the end of SUL treatment.. We conclude that treatment with SUL in patients with CVI reduces intravascular inflammation and is protective for the endothelial cells and for the extracellular matrix changes related to metalloproteinase expression.

Topics: Aged; Anti-Inflammatory Agents; Anticoagulants; Chemokine CCL2; Chronic Disease; Endothelial Cells; Female; Glycosaminoglycans; Humans; Inflammation; Interleukin-6; Male; Matrix Metalloproteinase 9; Middle Aged; Treatment Outcome; Venous Insufficiency

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

We evaluated the effects of the glycosaminoglycan sulodexide (SDX; antithrombotic/profibrinolytic drug) on the activity and release of matrix metalloproteinases (MMPs) in human blood. This was a prospective non-randomized study, analyzing by zymography and ELISA the in vitro effects of SDX on pro-enzyme, complexed, and active MMP forms in plasma and serum from 60 healthy donors, and in U-937 leukemia cell line. The levels and zymographic profile of MMP-2 did not show significant changes among samples and during SDX treatments. However, pro- and complexed forms of MMP-9 were strongly affected by SDX treatment (P<0.001), with significant decrease of MMP-9 secretion from white blood cells in a dose-dependent fashion (P<0.0001), without any displacement of MMP prodomains. The mechanism of reduced release of MMP-9 forms from leukocytes and inhibition of proteolytic activity due to SDX treatment may support the hypothesis that drugs based upon inhibitors of MMP-9 activity may provide a therapeutic tool for the underlying pathological destruction of extracellular matrix, and offering novel pharmacologic applications for chronic inflammatory vascular diseases, including varicose vein and chronic venous diseases associated with enhanced MMP activation in blood and limbs.

Topics: Adult; Chronic Disease; Collagen; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Female; Glycosaminoglycans; Humans; In Vitro Techniques; Leukemia; Leukocytes; Male; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Middle Aged; Prospective Studies; U937 Cells; Vascular Diseases

Sulodexide (Vessel 2F, Italy) was given to 20 patients with diabetes mellitus type I with initial nephropathy. Urine excretion of albumin significantly fell in 18 patients and remained so in 15 patients 6 weeks after the drug discontinuation. Plasma total cholesterol tended to lowering. No changes were registered in hemostasis and carbohydrate metabolism. The authors propose combined administration of sulodexide and inhibitors of angiotensin-converting enzyme for treatment and prevention of diabetic nephropathy progression.

Topics: Adult; Analysis of Variance; Chronic Disease; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Drug Evaluation; Female; Glycosaminoglycans; Humans; Hypoglycemic Agents; Male; Statistics, Nonparametric; Time Factors