s-5682 and Venous-Insufficiency

The author characterizes the edema as an important quantitative objective measure of severity for chronic venous diseases in both early and advanced stages. The problems of edema assessment methods and the importance of its management in clinical practice are discussed. The results of studies on the use of micronized purified flavonoid fraction (MPFF, Detralex) for edema syndrome coping are presented.

Topics: Chronic Disease; Diosmin; Drug Combinations; Edema; Hesperidin; Humans; Prognosis; Severity of Illness Index; Venous Insufficiency

Topics: Diosmin; Drug Combinations; Flavonoids; Hesperidin; Humans; Sclerotherapy; Varicose Veins; Vasodilator Agents; Venous Insufficiency; Venous Thrombosis

Microangiopathy of chronic venous insufficiency is characterized by elongated, dilated and coiled skin capillaries, which are surrounded by an enlarged pericapillary space (halo). Reduction of capillary number and even areas devoid of microvessels (atrophie blanche) are common in severe chronic venous insufficiency associated with focal microvascular ischaemia (decreased transcutaneous oxygen tension). The superficial network of skin lymphatic capillaries is obliterated in part. Oedema formation results from increased permeability of blood capillaries (enhanced transcapillary diffusion of sodium fluorescein) and deficient lymphatic drainage of interstitial fluid.

Topics: Diosmin; Drug Combinations; Flavonoids; Hesperidin; Humans; Lymphatic System; Lymphedema; Microcirculation; Microscopy, Fluorescence; Microscopy, Video; Skin; Venous Insufficiency

Daflon 500 mg consists of 450 mg diosmin and 50 mg flavonoid expressed as hesperidin. The authors describe its effects on the microcirculation in chronic venous insufficiency: improvement of venous tone, inhibition of prostaglandin synthesis, protection against free radicals, activation of the complement system, and increased lymphatic drainage. The authors summarize studies of its therapeutic efficacy in reducing venous capacitance, distensibility, and emptying time; reducing capillary permeability; and increasing capillary resistance.

Topics: Animals; Chronic Disease; Diosmin; Drug Combinations; Flavonoids; Hesperidin; Humans; Venous Insufficiency

Analyzed herein are the findings obtained following an examination and medical treatment of five 17-to-39-year-old male patients (average age 25.0+/-1.83 years) presenting with congenital abnormalities of the inferior vena cava. The diagnosis was made and the level of aplasia was determined based on the findings of a comprehensive instrumental examination (computed and magnetic resonance tomography of the abdominal cavity, duplex scanning of the veins of the lower extremities, of the pelvis and the retroperitoneal space, as well as on the data of pelvic phlebography, and retrograde cavography). In three of the five patients, the disease appeared to have for the first time manifested itself by a clinical picture of peripheral thrombosis (oedema of the crus and femur), and in the remaining two by an elevated body temperature and shivering, followed by oedema of the both lower limbs. Two patients were found to have aplasia of the infrarenal segment of the inferior vena cava, two subjects had aplasia of the infra-, renal and partially suprarenal portions of the vessel, and one patient suffered from aplasia of virtually the whole vena cava, excepting a small part of the suprahepatic portion, toward which converged the hepatic veins and the superior polar renal vein. With the purpose of early diagnosis of congenital abnormalities of the inferior vena cava, the protocol of examination of patients with venous diseases should include ultrasonographic mapping of the supra-, renal and infrarenal portions of the vena cava, and if agenesis is revealed, the use of computed or magnetic resonance tomography, retrograde cavography is strongly recommended. When the diagnosis of IVC aplasia is confirmed, primary medical treatment should consist in prescribing venotonic agents, elastic compression and in cases of deep veins thrombosis -anticoagulant therapy.

Topics: Adolescent; Adult; Diagnosis, Differential; Diosmin; Drug Combinations; Fibrinolytic Agents; Heparin; Hesperidin; Humans; Male; Ultrasonography, Doppler; Vascular Surgical Procedures; Vena Cava, Inferior; Venous Insufficiency

The aim of this clinical study was to compare the degree of postoperative pain (VAS--10 cm, quality of life questionnaire CIVIQ and patient diary) between two groups of patients: patients treated with Detralex 14 days before and 14 days after the stripping of greater saphenous vein (GSV) and patients not treated with Detralex. In addition, the two groups were also compared for the incidence of symptoms associated with chronic venous insufficiency (CVI) (using the VAS scale: edema, tired and heavy legs, cramps, itching sensation), size of hematoma, use of analgesics and overall efficacy of the treatment. Clinical study included 181 patients from 15 medical centers throughout the Czech Republic. High ligation and partial stripping of greater saphenous vein on one lower extremity was performed in all patients (short stripping from groin to knee). Patients were randomly assigned in two groups: patients treated with Detralex (92) and patients not treated with Detralex (89). Patients in the first group were treated with Detralex for the period of 1 month. Degree of pain and patient's health condition were evaluated by the physician during D-14 (14 days prior to the surgery), D7 and D14 (7 and 14 days after the surgery) visits using the 10-cm visual analog scale VAS. The results indicate that Detralex reduced the intensity of postoperative pain, which resulted in decreased consumption of analgesics. Hematoma was smaller in patients already using Detralex 14 days prior to the scheduled stripping procedure. These patients also showed significant improvement of CVI symptoms and the quality of life of patients with CVI. High quality venoactive drugs administered 14 days prior to the surgery improve postoperative course in patients indicated for surgical treatment of varices.

Topics: Adolescent; Adult; Chronic Disease; Diosmin; Drug Combinations; Hesperidin; Humans; Middle Aged; Pain Measurement; Pain, Postoperative; Postoperative Complications; Quality of Life; Saphenous Vein; Vascular Surgical Procedures; Venous Insufficiency

76 patients with severe venous insufficiency (CVI) entered the study. All the patients received 500 mg of Detralex twice daily for 2 months. The drug was well tolerated and relieved CVI symptoms in the majority of cases.

Topics: Chronic Disease; Diosmin; Drug Combinations; Flavonoids; Hesperidin; Humans; Tablets; Time Factors; Venous Insufficiency

During chronic venous insufficiency (CVI), microcirculatory changes, e.g. a decrease in transcutaneous oxygen pressure (tcpO2) and an increase in transcutaneous carbon dioxide pressure (tcpCO2), are implicated in the pathophysiology of trophic disorders leading ultimately to venous ulcers. Daflon 500 mg1, a micronized purified flavonoid fraction, has been shown to improve venous tone, capillary permeability and resistance, and lymphagogue activity at a daily dose of 2 tablets. To assess the effects of Daflon 500 mg on microcirculatory parameters by means of laser Doppler fluxmetry and transcutaneous oxiketry, a 3-month, double-blind, randomized, parallel-group study was carried out in 104 patients divided into 3 groups according to the daily dose: 1 tablet (group 1, n = 34), 2 tablets (group 2, n = 33), on 4 tablets (group 3, n = 37). All patients (mean age 43.7 +/- 13.1 years; 100 females, 4 males) included in the study were affected by mild CVI. They were followed for 90 days with visits at 1 month (day 28) and 3 months (day 90). At inclusion, there were no significant differences between groups as regards biometric data, mean tcpO2 (group 1, 62.7 +/- 4.5 mm Hg; group 2, 64.0 +/- 3.3 mm Hg; group 3, 64.1 +/- 3.5 mm Hg), mean tcpCO2 (group 1, 40.7 +/- 2.5 mm Hg; group 2, 39.3 +/- 2.9 mm Hg; group 3, 40.0 +/- 2.5 mm Hg) and laser Doppler parameters. Fourteen patients withdrew from the study (group 1, n = 4; group 2, n = 3; group 3, n = 7): 9 for reasons not related to treatment, 3 for adverse events, 2 because they were lost to follow-up. From day 0 to day 90, mean tcpO2 significantly increased (p < 0.001) in each group (group 1, 3.0 +/- 2.1 mm Hg; group 2, 2.9 +/- 2.1 mm Hg; group 3, 2.5 +/- 1.6 mm Hg), mean tcpCO2 significantly decreased (p < 0.001) in each group (group 1, 2.6 +/- 2.0 mm Hg; group 2, 1.7 +/- 1.9 mm Hg; group 3, 2.2 +/- 1.5 mm Hg). No significant differences were observed between groups. Laser Doppler parameters remained unchanged from day 0 to day 90 in the 3 groups. Symptoms (discomfort, pain, heaviness, burning sensation) and signs (oedema) of CVI as well as perimetric measurements of calf and supramalleolar area were significantly improved in the 3 groups. In conclusion, during this 3-month study, Daflon 500 mg improved oximetric measurements and did not alter laser Doppler parameters. These data suggest that Daflon 500 mg, at the early stages of CVI, acts favourably on the microcirculatory disturbances also involved in the pathophys

Topics: Adult; Blood Gas Monitoring, Transcutaneous; Diosmin; Double-Blind Method; Drug Combinations; Female; Flavonoids; Hesperidin; Humans; Laser-Doppler Flowmetry; Male; Microcirculation; Middle Aged; Skin; Venous Insufficiency

In the more advanced stages of chronic venous insufficiency, stasis in the skin microcirculation is associated with a decreased red blood cell velocity and an increase in packed cell volume related to the red blood cell piling phenomenon. Although the main factor determining blood viscosity is packed cell volume, the direct relationship between this variable, viscosity and velocity is no longer valid at the microcirculatory level (sigma effect). Viscosity is influenced by blood composition and red blood cell deformability. The aim of this open pilot study was to verify the variations in capillary packed cell volume in comparison with the velocity in 24 patients with third-stage chronic venous insufficiency before (day 1) and after (day 28) a 28-day treatment with Daflon 500 mg, a micronized purified flavonoid fraction consisting of diosmin, 450 mg, and hesperidin, 50 mg, per tablet, 1 g/day, and then 14 days (day 42) after cessation of treatment. Ankle skin microcirculation was evaluated by dynamic capillaroscopy. Values of relative capillary packed cell volume were calculated by a densitometric method, and red blood cell velocity was calculated using the cross-correlation simplified method. Relative capillary packed cell volume (mean +/- SD) significantly (p = 0.001) increased from day 1 (64.10 +/- 9.34%) to day 28 (72.89 +/- 5.74%) and then decreased until day 42 (66.84 +/- 7.48%). In the same patients, red blood cell velocity (mean +/- SD) significantly (p = 0.041) increased from day 1 (0.26 +/- 0.14 mm/sec) to day 28 (0.35 +/- 0.11 mm/sec) and then remained stable until day 42 (0.33 +/- 0.16 mm/sec). Two possible explanations can account for this apparent discrepancy: first, dissociation between viscosity and velocity due to the Fahraeus-Lindqvist effect (sigma effect); and secondly, increased deformability of red blood cells leading to an increased red blood cell velocity despite an increased packed cell volume. It can be concluded that Daflon 500 mg seems to have a beneficial haemorheological effect, resolving the stasis with an increase in red blood cell velocity. A concomitant increase in relative packed cell volume and red blood cell velocity after therapy suggests an improvement of the flexibility of red blood cells.

Topics: Adult; Aged; Diosmin; Drug Combinations; Female; Flavonoids; Hesperidin; Humans; Male; Microcirculation; Microscopy, Fluorescence; Microscopy, Video; Middle Aged; Rheology; Skin; Venous Insufficiency

A randomized, double-blind, multicenter trial was performed to study the pharmacodynamic and clinical activities of Daflon 500 mg,* in comparison with a nonmicronized diosmin. Daflon 500 mg is a micronized purified flavonoidic fraction consisting of 450 mg of diosmin and 50 mg of hesperidin per tablet, which has been micronized in order to ensure a better gastrointestinal absorption. Ninety patients with chronic venous insufficiency of the lower limbs, stabilized for one year, entered the study. They received either two tablets of Daflon 500 mg or an equivalent dose of nonmicronized diosmin in two divided doses each day during two months. The following parameters were studied: functional clinical symptoms in the lower extremities, ankle circumference measurement, strain gauge plethysmographic parameters with 20, 40, and 60 mmHg venous occlusion, and clinical and biochemical acceptability. Statistically significant changes were obtained in both groups of patients in comparison with baseline values. However, the improvements in all clinical symptoms and plethysmographic parameters (maximum increase of venous volume at 60 mmHg and total time for emptying) were significantly better with Daflon 500 mg than with nonmicronized diosmin. The clinical and laboratory acceptability was similar in both groups. However, the percentage of satisfied patients was 95% in the Daflon 500 mg group, versus 80% in the nonmicronized diosmin group (p < 0.01). In conclusion, the pharmacodynamic and clinical activities of Daflon 500 mg are superior to those of an equivalent dose of nonmicronized diosmin and demonstrate the therapeutic advantage of a micronized formulation in the treatment of chronic venous insufficiency.

Topics: Adult; Chronic Disease; Diosmin; Dosage Forms; Double-Blind Method; Drug Combinations; Female; Flavonoids; Hesperidin; Humans; Male; Middle Aged; Patient Satisfaction; Plethysmography; Venous Insufficiency

Although great advances have been made in the operative treatment of vascular disorders, the management of most venous problems is still nonsurgical. Daflon 500 mg* is a micronized flavonoid mixture of 90% diosmin and 10% hesperidin that has phlebotonic properties. The efficacy of Daflon 500 mg has been investigated in three double-blind, randomized trials using strain gauge plethysmography to provide quantitative information on venous hemodynamics in patients with chronic venous insufficiency. In total, 183 patients were treated with Daflon 500 mg versus a control group of equal number of patients. Daflon 500 mg produced a significant decrease in venous capacitance, venous distensibility, and venous emptying time (P < 0.001). In addition, these changes were accompanied by improvement in clinical symptoms and a decrease in the supramalleolar circumference. Clinical side effects were rare and led to treatment withdrawal in only 3 patients. It is concluded that Daflon 500 mg is of benefit to patients with chronic venous insufficiency.

Topics: Diosmin; Drug Combinations; Flavonoids; Hesperidin; Humans; Plethysmography; Randomized Controlled Trials as Topic; Venous Insufficiency

Abstract The results of 1142 patients treatment for varicose disease of the lower extremities in 2006-2014 yrs were adduced. The patients were divided on 3 groups, depending on the clinical signs severity and method of treatment. There were operated 59 patients, in 65--the proposed scheme of treatment was applied.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Angioplasty; Antioxidants; Diosmin; Disease Management; Drug Combinations; Female; Heme; Hesperidin; Humans; Lower Extremity; Male; Middle Aged; Retrospective Studies; Saphenous Vein; Sclerotherapy; Severity of Illness Index; Silicones; Sorption Detoxification; Treatment Outcome; Varicose Veins; Venous Insufficiency

Venous hypertension combined with other pathogenetic links of the development of chronic venous insufficiency creates conditions for activation of an inflammatory process. Chronization of inflammation leads to alterations in the histological structure of the vascular wall and perivasal tissues, which is reflected by changes in their physical properties (elasticity or compressibility), which may be studied by means of ultrasound elastography (USEG).. The study was aimed at exploring the possibility of using ultrasound elastography for monitoring efficacy of conservative treatment of varicose disease of lower extremities with an agent containing a micronized purified flavonoid fraction (MPFF).. we examined a total of 19 patients (38 limbs) presenting with varicose disease of clinical class C2 according to the CEAP classification. The standard ultrasound examination and USEG were carried out using the unit of expert-class "Toshiba" (Japan) with a multi-frequency linear transducer 5-12 Hz. We examined the great saphenous vein in the area of the femur and crus, its tributaries, and the small saphenous vein. All examinations were performed with the patient in the supine, prone and standing positions from the standard approaches in the second half of the day prior to treatment with a phlebotrophic agent containing MPFF (Detralex) and three months after taking the drug at a dose of 1,000 mg/day.. at baseline, according to the findings of USEG the intact veins of the lower limbs had a homogeneous pattern of the elastogram in the perivasal area. The presence of varicose transformation was associated with an inhomogeneous elastographic picture. On the background of treatment with MPFF, all patients showed a positive clinical effect in the form of decreased intensity of manifestations of complaints or complete disappearance thereof. According to the findings of ultrasound examination, there was a tendency towards a decrease in the wall thickness and diameter of the examined veins. USEG demonstrated an increase in the perivasal zones of elastographic homogeneity of tissues. The USEG-revealed alterations were more pronounced in large-diameter vessels. On the background of treatment with Detralex there was a trend towards normalization of the elastographic pattern of the vessel as a whole.. the obtained findings confirm feasibility of using the technique of ultrasound elastography for identification of objective markers of treatment response to MPFF in varicose disease.

Topics: Biological Availability; Diosmin; Drug Combinations; Drug Monitoring; Elasticity; Elasticity Imaging Techniques; Feasibility Studies; Female; Flavonoids; Hesperidin; Humans; Lower Extremity; Male; Middle Aged; Phlebitis; Saphenous Vein; Severity of Illness Index; Treatment Outcome; Varicose Veins; Venous Insufficiency

The work presents an analysis of results of conservative treatment of 48 patients aged from 32 through 76 years having postthrombophlebitic syndrome with symptoms of chronic venous insufficiency. The system of complex pharmacotherapy included phlebothropic medicines of flavonoid series (detralex) and of synthetic origin (tribenosid). The course of treatment was 2-3 months. Long-term results of the treatment were followed-up during the period from 6 months to 2 years in 44 patients. The complex treatment resulted in reliably less degree of clinical manifestations (chronic venous insufficiency). Recurrence of trophic ulcers appeared in 6 patients.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Blood Flow Velocity; Blood Viscosity; Chronic Disease; Diosmin; Drug Combinations; Drug Therapy, Combination; Female; Follow-Up Studies; Foot Ulcer; Glycosides; Hesperidin; Humans; Leg; Male; Middle Aged; Phlebography; Recurrence; Severity of Illness Index; Thrombophlebitis; Time Factors; Treatment Outcome; Ultrasonography, Doppler, Duplex; Venous Insufficiency

To verify incidence of risk factors of chronic venous insufficiency (CVI) of the lower limbs and efficacy of outpatient treatment.. A total of 4388 patients were examined by questioning and examination of the lower limbs. 1209 patients with CVI stages C1, C2 and C3 were included in the study. They received recommendations to use elastic compression, topic modalities, physiotherapy. Patients of the study group were given, in addition, detralex for 8 weeks.. Characteristic symptoms of CVI were seen in 68% males and 84% females but only 17.5 and 20%, respectively, had complaints. The risk was highest in history of CVI in the patient's mother, sitting or standing job, hard physical labour, obesity and constipation, two or more labours in women. The effect was achieved in the detralex group.. Many outpatients had symptoms of chronic venous insufficiency but had no complaints. Detralex therapy proved highly effective in outpatient practice.

Topics: Adolescent; Adult; Age Factors; Aged; Bandages; Chronic Disease; Constipation; Diosmin; Drug Combinations; Exercise Therapy; Female; Hesperidin; Humans; Incidence; Leg; Male; Middle Aged; Obesity; Risk Factors; Sex Factors; Treatment Outcome; Venous Insufficiency

Topics: Diosmin; Drug Combinations; Flavonoids; Hemorrhoids; Hesperidin; Humans; Venous Insufficiency

A research program has been developed to define an evaluation tool capable of assessing the impact of venous insufficiency and its treatments on the patient's everyday life. The methodology is described in the first part of this paper, followed by the results of the first phase of the research program, based on two surveys: a "qualitative" survey in a population of severely affected patients and a "quantitative" survey in a population of 150 patients.

Topics: Activities of Daily Living; Adolescent; Adult; Aged; Aged, 80 and over; Diosmin; Drug Combinations; Female; Flavonoids; Hesperidin; Humans; Male; Middle Aged; Pain; Quality of Life; Varicose Veins; Venous Insufficiency

Over recent years, a number of functional investigations have been developed that allow a better evaluation of the physiology of the cutaneous microcirculation than that provided by the morphologic method. These investigations are also useful in pharmacologic studies. Following a review of the anatomy and physiology of the cutaneous microcirculation, the author presents the principal techniques of investigation and the results obtained with Daflon 500 mg* on the cutaneous microcirculation evaluated by photoplethysmography of the skin in patients with venous insufficiency and leg ulcers.

Topics: Blood Pressure; Diosmin; Drug Combinations; Flavonoids; Hesperidin; Humans; Leg Ulcer; Microcirculation; Photoplethysmography; Skin; Varicose Ulcer; Venous Insufficiency

Daflon 500 mg is a new flavonoid vasoprotector venotonic agent whose active principle is micronized and contains 90% diosmin and 10% flavonoids expressed as hesperidin. In animal studies, the safety of Daflon 500 mg is shown by an LD50 (lethal dose 50) of more than 3 g/kg, ie, 180 times the daily therapeutic dose, as well as by the absence of any toxic effect after repeated oral dosing for thirteen and twenty-six weeks, using a dose representing 35 times the daily dosage, in the rate and primate. Daflon 500 mg has no mutagenic action nor any significant effect on reproductive function. Gastrointestinal tolerance is good when administered orally in the rat. Transplacental passage and passage into breast milk are minimal. In the rat, 0.003% of the administered dose has been found in each fetus and 1% in breast milk. Clinical trials fulfill international scientific requirements and have collected more than 2850 patients treated with Daflon 500 mg at the dosage of two tablets per day for six weeks to one year. The proportion of patients with side effects (10% of those treated), essentially of a gastrointestinal or autonomic nature and leading to a rate of only 1.1% trial dropouts, is less than described in 225 patients given a placebo (13.9%) in controlled trials. Satisfactory clinical acceptability already confirmed in the short term was equally found in long-term treatment. Hemodynamic parameters (systolic and diastolic blood pressure) as well as laboratory parameters (hematology, liver and renal function, metabolic) were uninfluenced even by prolonged treatment for one year at the dosage of two tablets per day.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Clinical Trials as Topic; Diosmin; Drug Combinations; Flavonoids; Hemorrhoids; Hesperidin; Humans; Mice; Rats; Rats, Wistar; Venous Insufficiency