Intravesical instillation with glycosaminoglycan replacement treatment in patients suffering radiation-induced haemorrhagic cystitis: When and which patients can benefit most from it?

INTRODUCTION & OBJECTIVES: Radiation-induced haemorrhagic cystitis (RHC) is a frightening complication occurring after pelvic radiotherapy (PRT) which may significantly affect patients' quality of life. Bladder instillation with glycosaminoglycan replacement therapy (GRT) including hyaluronic acid +/- chondroitin sulphate has been proposed as an emerging alternative to prevent relapses of haematuria. Strong points in favour of using GRT for RHC are the ease of administration, cost, almost absence of side effects and possibility of administration to outpatients. We investigated the effectiveness of GRT in a cohort, single-centre, of patients with past-medical history of PRT attending the outpatient clinic and/or the accident & emergency department (A&E) for RHC. MATERIALS & METHODS: Patients with diagnosis of RHC, either with toxicity grade of 2 or 3, were deemed candidate for GRT as long as no active bleeding was occurring; in the case of non-self-limiting haematuria and/or anaemia for active bleeding, admission in the urology department was prompted for bleeding control prior to GRT instillation. An induction course of 6 weekly instillations was scheduled; if tolerated, patients were given a maintenance course with at least 6 monthly instillations. The primary end-point consisted in assessing the rate of haematuria remission (either partial or complete) defined as no need to readmission in the A&E and/or in the hospital. Secondary end-points included factors related to GRT failure. Univariate and multivariate analysis were undertaken to identify clinical independent variables associated to the events. RESULTS: Fifty-one patients with at least 1-year follow-up from the first GRT were included in the analysis. 88.2, 9.8 and 2% of patients had undergone PRT because affected by prostate, uterus and colorectal cancer, respectively. Median time-to-RHC was 31 months (IQR 21-90). Access to A&E and hospital admission were needed in 47 (92.1%) and 35 (68.6%) of the patients, respectively. Twenty-two (n = 22/35, 62.9%) patients required transurethral fulguration of the bladder, while the remainders could be managed with bladder wash-out. Median number of GRT instillations was 6 (IQR 3-7). Twenty-three (45.1%) patients needed to be readmitted to hospital a second time, receiving bladder wash-out (n = 7/23, 30.4%), transurethral fulguration of the bladder (n = 10/23, 43.5%) and/or cystectomy (n = 6/23, 26.1%). Ten (19.6%) patients received a second induction course of GRT. At the last follow-up, 36 (70.6%) patients did not required further hospital admission. Type of PRT and number of hospital admissions pre-GRT were the only variables statistically associated to the events at both univariate (P = 0.032 and P = 0.045) and multivariate analysis (P = 0.048 and P = 0.049). CONCLUSIONS: GRT should be prompted as soon as possible after diagnosis of the haematuria and settling of active bleeding. Patients who had undergone adjuvant PRT after radical prostatectomy are those at higher risk of GRT failure.

Efficacy of biodegradable collagen matrix (Ologen® CM) in augmenting the success rate of Ahmed glaucoma valve implantation in canine glaucoma.

OBJECTIVE: To prospectively assess the efficacy of a biodegradable collagen matrix (ologen) in dogs with uncontrolled glaucoma receiving an Ahmed glaucoma valve (AGV) implant. ANIMAL STUDIED: Five client-owned dogs with glaucoma (five eyes). PROCEDURES: Five eyes treated for uncontrolled glaucoma underwent AGV implantation with ologen. Ologen was placed on the AGV plate and tube with a scleral flap. Complete ophthalmological examinations were performed preoperatively and at 1 and 3 days, 1 and 2 weeks, and 1, 2, 3, and 6 months postoperatively. Surgical outcomes were assessed based on the intraocular pressure (IOP), vision, frequency of anti-glaucoma eye drops, and bleb morphology; complications, if any, were recorded. The number of dogs with an IOP <20 mmHg with or without topical medications were tabulated and compared to those with an IOP ≥20 mmHg or those requiring surgery to maintain the IOP at <20 mmHg. RESULTS: The IOP significantly decreased from 47.00 ± 5.09 mmHg preoperatively to 17.00 ± 0.71 mmHg 6 months postoperatively (p = .008). IOP was controlled (<20 mmHg) in 5/5 dogs at 6 months postoperatively. Brief periods of elevated IOP (IOP ≥ 20 mmHg, IOP spike) occurred in one eye (case 5) at 1 month (35 mmHg) and 2 months (33 mmHg) postoperatively. The anti-glaucoma eye drop frequency decreased from 3.2 ± 0.44 preoperatively to 1.6 ± 0.90 at 6 months postoperatively (p = .007). CONCLUSIONS: To our knowledge, this is the first study to assess the potential safety of AGV implantation with ologen for canine glaucoma. This method effectively controlled the IOP, without any adverse effects.

Offspring of Obese Dams Exhibit Sex-Differences in Pancreatic Heparan Sulfate Glycosaminoglycans and Islet Insulin Secretion.

Offspring of obese mothers suffer higher risks of type 2 diabetes due to increased adiposity and decreased ß cell function. To date, the sex-differences in offspring islet insulin secretion during early life has not been evaluated extensively, particularly prior to weaning at postnatal day 21 (P21). To determine the role of maternal obesity on offspring islet insulin secretion, C57BL/6J female dams were fed chow or western diet from 4 weeks prior to mating to induce maternal obesity. First, offspring of chow-fed and obese dams were evaluated on postnatal day 21 (P21) prior to weaning for body composition, glucose and insulin tolerance, and islet phasic insulin-secretion. Compared to same-sex controls, both male and female P21 offspring born to obese dams (MatOb) had higher body adiposity and exhibited sex-specific differences in glucose tolerance and insulin secretion. The male MatOb offspring developed the highest extent of glucose intolerance and lowest glucose-induced insulin secretion. In contrast, P21 female offspring of obese dams had unimpaired insulin secretion. Using SAX-HPLC, we found that male MatOb had a decrease in pancreatic heparan sulfate glycosaminoglycan, which is a macromolecule critical for islet health. Notably, 8-weeks-old offspring of obese dams continued to exhibit a similar pattern of sex-differences in glucose intolerance and decreased islet insulin secretion. Overall, our study suggests that maternal obesity induces sex-specific changes to pancreatic HSG in offspring and a lasting effect on offspring insulin secretion, leading to the sex-differences in glucose intolerance.

Sulodexide in the Treatment of Patients with Early Stages of COVID-19: A Randomized Controlled Trial.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may induce several vascular endothelial-dependent systemic complications, and sulodexide has pleiotropic actions on the vascular endothelium, which may prove beneficial. We aimed to assess the effect of sulodexide when used within 3 days of coronavirus disease 2019 (COVID-19) clinical onset. We conducted a randomized placebo-controlled outpatient trial. To be included, patients must have been at high risk for severe clinical progression. Participants received sulodexide (oral 1,000 LRU/d) or placebo for 21 days. The primary endpoint was the need for hospital care. Also assessed were patients' need for supplemental oxygen as well as D-dimer and C-reactive protein (CRP) levels, thromboembolic events, major bleeding, and mortality. A total of 243 patients were included in the per-protocol analysis from June 5 to August 30, 2020. Of these, 124 received sulodexide and 119 received a placebo. Only 17.7% of the patients in the sulodexide group required hospitalization, compared with 29.4% in the placebo group (p = 0.03). This benefit persisted in the intention-to-treat analysis (15% in sulodexide group vs. 24% with placebo [p = 0.04]). With sulodexide, fewer patients required supplemental oxygen (30 vs. 42% [p = 0.05]). After 2 weeks, fewer patients had D-dimer levels >500 ng/dL (22 vs. 47% [p < 0.01]), and patients also had lower mean CRP levels (12.5 vs. 17.8 mg/dL [p < 0.01]). There were no between-group differences in thromboembolic events, major bleeding, or mortality. Treatment of COVID-19 patients with sulodexide, when provided within 3 days of clinical onset, improved their clinical outcomes. Although the results should be confirmed, sulodexide could be valuable in an outpatient setting.

Reducing hyperpigmentation after sclerotherapy: A randomized clinical trial.

OBJECTIVE: 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. METHODS: 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 χ2 test were used for comparative analyses, as appropriate. The level of significance was set at P < .05. RESULTS: 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. CONCLUSIONS: 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.

Sulodexide for the Symptoms and Signs of Chronic Venous Disease: A Systematic Review and Meta-analysis.

INTRODUCTION: 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. METHODS: 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 I2). RESULTS: 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; I2 = 0%; 270 participants). The overall risk of AEs with sulodexide was low: 3% (95% CI 1-4%) estimated from 3656 participants. CONCLUSION: 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.

Recurrent retinal vein thrombosis: prevention with Aspirin, Pycnogenol®, ticlopidine, or sulodexide.

BACKGROUND: The aim of this study is to evaluate the use of Aspirin, Pycnogenol®, ticlopidine, and sulodexide to reduce the incidence of new RTV (retinal vein thrombosis) after a first episode. Pycnogenol® is an anti-inflammatory, anti-edema, mild antiplatelet-antithrombotic agent. METHODS: The registry study evaluated the number of repeated episodes of RVT in 12 months. Possible managements were: standard management (SM); SM + Aspirin (100 mg/once day; if there were no tolerability problems); SM + Pycnogenol (100 mg/day); SM and ticlopidine (200 mg/day); SM + sulodexide (500 ULS/day). The number of subjects age and sex, distribution, the percent of smokers, the vision were comparable at inclusion. RESULTS: 307 subjects completed the study, 44 in the SM group, 90 in the Pycnogenol® group, 90 in the aspirin group, 45 in the ticlopidine group and 38 in the sulodexide group. At 12 months, recurrent RVT was documented in 22.7% of controls (SM), 3.3% of Pycnogenol® subjects (P<0.05 vs. SM; 19.4% difference). There were RVTs in 15.5% subjects using Aspirin (-7.2% vs. SM). Ticlopidine also reduced (P<0.05) the incidence of RVT in comparison with SM (-9.1%). Sulodexide reduced the occurrence of new RVT (-9.5% vs. SM). Edema was better controlled with the supplement than with all other treatments (P<0.05) (edema present in only 5.5% of the Pycnogenol® subjects). Pycnogenol® had a very good tolerability and safety profile (no patient had to stop treatment). CONCLUSIONS: Pycnogenol® is the only product able to control edema and this may reduce the incidence of recurrent RVT. This retrospective registry indicates that Aspirin, Pycnogenol®, ticlopidine an sulodexide reduce recurrent RVT without side effects. Larger studies should be planned to involve a wider range of conditions, diseases and risk factors associated with RVT and to its recurrence.

Sulodexide in venous disease.

Sulodexide is a glycosaminoglycan extracted from porcine intestinal mucosa. The purpose of this review is to discuss sulodexide's complex pharmacological profile and its clinical applications for venous disease. Sulodexide has wide-ranging biological effects on the vascular system, including antithrombotic, profibrinolytic, anti-inflammatory, endothelial protective and vasoregulatory effects. Sulodexide has emerged as a potential therapeutic option for the management of chronic venous insufficiency, including venous ulceration, and the prevention of recurrent venous thromboembolism, with a low rate of major bleeding complications. Sulodexide's pleiotropic vascular effects may facilitate the management of common venous disorders.

Assessment of the effect of mesoglycan in the treatment of audiovestibular disorders of vascular origin.

It is a well-known fact that inner ear diseases are often caused by microcirculatory disorders, and the recent literature is oriented towards investigations into the relationship between the cardiovascular system and cochleovestibular illness with related classical symptoms: tinnitus, hearing loss, and vertigo or instability. These symptoms, and particularly the vertigo, may be the alarm signal of microcirculatory disorders of the labyrinth or vertebrobasilar circulation so as to represent a possible symptom of posterior circulation stroke. The treatment aimed at correcting the haemodynamic and metabolic imbalance, generated by the cochleovestibular microcirculatory disorders, with drugs that act on the vessel wall being very useful, both alone and in combination with other treatment protocols. This is a multicenter retrospective observational study conducted in 40 neurootological laboratories with 873 patients with cardiovascular risk factors suffering from tinnitus, instability or peripheral vertigo alone or in combination with one another treated for the first time with mesoglycan. The data collected showed that the treatment with mesoglycan, irrespective of the type of vascular risk factor, is not only well tolerated but also significantly and objectively improves the cochleovestibular symptoms and the quality of life of patients suffering from tinnitus, peripheral vertigo and instability.

Prevention of recurrent venous thrombosis and post-thrombotic syndrome.

BACKGROUND: This retrospective registry study evaluated different managements on the development of post-thrombotic syndrome (PTS) and recurrent deep venous thrombosis (R-DVT). The effects of aspirin (100 mg/day), added to the "standard management" (SM) (IUA consensus), were observed in patients after a proximal DVT. METHODS: The study started after the anticoagulant period. Comparable groups used the mild-antithrombotic agent Pycnogenol® (200 mg/day), ticlopidine (250 mg/day) or sulodexide (500 ULS/day). RESULTS: The groups were comparable for sex and age distribution and clinical pictures. In the SM group, 222 patients completed the follow-up (72 months). With SM, the percentage of patients with R-DVT (requiring anticoagulants) was 17.2%; 19.8% of SM patients had a PTS. In the aspirin group (202 subjects), R-DVT was observed in 14.8% of patients; 17.32% had a PTS. The reduction in R-DVT and PTS with aspirin was significant (P<0.05) vs. the SM. There was no tolerability problem in subjects using Pycnogenol® (137 patients); they had a much lower incidence of R-DVT (5.8%) and PTS (6.5%) vs. SM and aspirin (P<0.05). Ticlopidine (121 patients) reduced the incidence of R-DVT (12.4%) and PTS (19.8% of patients) (P<0.05 vs. SM). With sulodexide the incidence of R-DVT was 6.7% (P<0.05 vs. SM); the incidence of PTS was 16.6% (P<0.05 vs. SM). The combined R-DVT+PT syndrome was observed in 14.9% of subjects using SM and in 12.9% of subjects using aspirin (P<0.05 vs. SM), in 3.6% of subjects managed with Pycnogenol® (<0.05% vs. aspirin and all other managements). The incidence was 10.74% with ticlopidine and 6.7% with sulodexide (both significantly lower than SM). CONCLUSIONS: Interaction between PTS and R-DVT are complex; recurrences cause more PTSs, and a post-thrombotic limb is prone to R-DVT. Aspirin, for patients that can tolerate it, reduces the occurrence of PTS and R-DVT. In addition, ticlopidine and sulodexide are effective. Pycnogenol® is the most effective and safe for R-DVT and particularly PTS. Its full range of anti-thrombotic activity is now under evaluation.

[Sulodexide in treatment of chronic venous insufficiency. Results of the All-Russian multicenter programme ACVEDUCT]. / Sulodeksid v lechenii khronicheskoi venoznoi nedostatochnosti. Itogi Vserossiiskoi mul'titsentrovoi programmy ACVEDUCT.

INTRODUCTION: Pharmacotherapy occupies one of the leading places in comprehensive treatment of lower-limb chronic venous diseases (CVD) and their complications. At the same time, there are not so many therapeutic agents intended for treatment of CVD and possessing evidence-based efficacy. Sulodexide (registered in Russia as Vessel Due F) is a drug with a confirmed therapeutic effect in patients with a moderately severe course of chronic venous disease or its late stages. However, the experience of using it in Russia for treatment of patients presenting with initial manifestations of chronic venous insufficiency (CVI) is still scarce. PATIENTS AND METHODS: The data concerning the use of Vessel Due F in the routine practice of treating CVD in Russian patients were collected and assessed within the framework of the ACVEDUCT programme. This observational prospective non-controlled multicentre programme included patients routinely prescribed by their attending physician Vessel Due F as a solution for injections and/or soft capsules in accordance with the registered in the Russian Federation instruction for use. A total of 2,263 patients took part in the programme. RESULTS: The majority of the patients prescribed sulodexide were diagnosed as having CEAP class C3 (38.4%) and class C4 (35.6%) CVD. Treatment was accompanied and followed by a decrease in the symptoms' severity observed in 56.4% of patients and a decrease in the number of symptoms in 42.8% of patients (thus positive dynamics was totally noted in 99.2%), with the effect of taking the drug commencing to manifest itself in patients as early as on day 15-20 of treatment. The highest rate of regression of symptoms of CVD was observed in 30-to-40-year-old patients. A statistically significant positive correlation was revealed between efficacy and the duration of treatment, the use of capsules during the term of follow up, with a negative correlation revealed between efficacy of treatment and the patient's age at which the diagnosis had been made, the stage according the CEAP classification, the total number of symptoms, a combination of risk factors. CONCLUSIONS: Sulodexide proved to be an effective, safe, well-tolerated and pathogenetically substantiated pharmacological agent for treatment of patients presenting with lower-limb CVI and should therefore be recommended for patients at early stages of formation of CVD. Patients suffering from venous trophic ulcers require higher doses and prolonged administration of the drug.

Chronic venous disease treated with sulodexide: a survey among primary care physicians in Mexico.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Sulodexide was effective and well tolerated in the treatment of CVD.

A semi-synthetic glycosaminoglycan analogue inhibits and reverses Plasmodium falciparum cytoadherence.

A feature of mature Plasmodium falciparum parasitized red blood cells is their ability to bind surface molecules of the microvascular endothelium via the parasite-derived surface protein Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1). This ligand is associated with the cytoadherence pathology observed in severe malaria. As pRBC treated with effective anti-malarial drugs are still able to cytoadhere, there is therefore a need to find an adjunct treatment that can inhibit and reverse the adhesion process. One semi-synthetic, sulfated polysaccharide has been identified that is capable of inhibiting and reversing sequestration of pRBC on endothelial cells in vitro under physiological flow conditions. Furthermore, it exhibits low toxicity in the intrinsic (APTT assay) and extrinsic (PT assay) clotting pathways, as well as exhibiting minimal effects on cell (HUVEC) viability (MTT proliferation assay). These findings suggest that carbohydrate-based anti-adhesive candidates may provide potential leads for therapeutics for severe malaria.

[Efficacy of sulodexide in treatment of chronic venous insufficiency. Results of the ACCORD trial]. / Éffektivnost' sulodeksida pri lechenii khronicheskoi venoznoi nedostatochnosti. Rezul'taty issledovaniia ACCORD.

OBJECTIVE: The purpose of our study was to evaluate both clinical and laboratory efficacy of sulodexide given at a daily dose of 500 lipasemic units (LSU) in patients presenting with class C3-C4 chronic venous insufficiency (CVI) according to the CEAP classification. PATIENTS AND METHODS: The study included a total of 25 patients diagnosed with C3-C4 CVI and prescribed to receive sulodexide at a daily dose of 500 LSU for 90 days. Efficacy was comprehensively controlled by the following tools: the disease-specific Chronic Venous Insufficiency Quality of Life Questionnaire (CIVIQ), visual-analogue methods of assessment separate symptoms; the Venous Clinical Severity Score (VCSS), as well as ultrasonographic determination of the thickness of subcutaneous fat and crural fascia. Amongst the key laboratory indices determined by means of the ELISA test were the levels of interleukin-1 alpha (IL-1α), interleukin-1 beta (IL-1ß), matrix metalloproteinases-2 and -9 (MMP-2, MMP-9), vascular endothelial growth factor A (VEGF-A), vasopressin and endothelin. RESULTS AND DISCUSSION: Of the initially enrolled 25 subjects, twenty-two patients completed the study and were taken as 100%. The 90-day treatment yielded favourable results manifesting themselves in complete disappearance of convulsions in the calf muscles detected at the first visit in 22.7% of patients (p=0.0485), a significant reduction in the frequency of complaints of decreased tolerance to static loads from 27.3 to 9.1% (p=0.2404). The volume of the crus of the control lower extremity decreased from 134.18±14. 92 to 128.42±12.46 cm3 (p=0.0006), subcutaneous fat thickness at the fixed point decreased from 1.50±0.53 to 1.32±0.46 cm (p=0.0007), and fascial thickness decreased from 0.14±0.7 to 0.11±0.04 (p=0.0359). Pain syndrome according to the visual analogue scale (VAS) decreased from 36.45±25.60 to 17.50±19.27 mm (p=0.0002). The global index of quality of life (GIQoL) according to the CIVIQ-20 increased by 27.7% compared with the baseline level (p = 0.0001), the VCSS index decreased from 6.00±1.83 to 4.86±2.05 points (p=0.0002). as for the laboratory markers of endothelial dysfunction, there was a significant decrease in the levels of MMP-2 - from 178.53±36.30 to 176.35±36.67 ng/ml (p=0.0152), MMP-9 - from 90.84±20.41 to 89.78±20.32 ng/ml (p=0.0394), and that of endothelin - from 0.42±0.10 to 0.39±0.10 fmol/ml. CONCLUSION: Sulodexide exerting a statistically significant clinical and endothelium-protecting effect turned out to be an effective drug for treatment of initial forms of chronic venous insufficiency of lower limbs.

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

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 [...].

Sulodexide in Patients with Chronic Venous Disease of the Lower Limbs: Clinical Efficacy and Impact on Quality of Life.

INTRODUCTION: 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. METHODS: 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)]. RESULTS: 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). CONCLUSION: Oral sulodexide significantly improves both objective and subjective symptoms, as well as functional and psychological aspects of QoL in patients with CVD. FUNDING: No funding or sponsorship was received for this study. Sponsorship for article processing charges and open access fees was provided by Alfa Wassermann.