beta-escin and Varicose-Veins

The involvement of the microvascular structure in chronic venous insufficiency (CVI) causes venous hypertensive microangiopathy (VHM), which leads to venous ulceration. VHM is characterized by enlarged and ramified capillaries, increased flux and capillary permeability, edema, and altered function of microlymphatics. TcPO2 is decreased and CO2 increased. This perfusional paradox is caused by hyperperfusion in the deep skin layers with hypoperfusion of superficial nutritional capillaries. Exchanges in the capillary bed are altered. Nutritional skin alterations eventually lead to venous ulceration. Edema is the consequence of increased capillary pressure, reduced clearance, and by an increased exchange surface of capillaries. The aim of this randomized, placebo-controlled study was to evaluate the effect of local treatment with Essaven gel (EG) in 22 subjects with VHM due to severe varicose veins, treated with a single application. Measurements of flux, PO2 and PCO2 in standardized conditions of application indicated a significant decrease of the abnormally increased flux and CO2; PO2 increased in the treatment group. Essaven gel, in comparison with placebo and controls acutely improves the microcirculation in VHM even with a single application.

Topics: Administration, Topical; Adult; Double-Blind Method; Drug Combinations; Escin; Female; Fibrinolytic Agents; Heparin; Humans; Hypertension; Male; Microcirculation; Middle Aged; Phospholipids; Skin; Varicose Veins

The aim of this randomized, placebo-controlled study was to evaluate the effect of local treatment with Essaven gel (EG), in comparison with placebo in 30 patients with superficial vein thrombosis (SVT). The 8-week study evaluated SVT with an analogue clinical/symptomatic score. SVT was associated with varicose veins. In patients treated with active EG the decrease in score was significantly larger (p< 0.02) than in the placebo group. No intolerance was observed. The decrease in score in the placebo group was due to spontaneous resolution and to skin manipulation and massage. In conclusion local treatment with EG in SVT improves signs/symptoms much faster than placebo. This study confirms earlier observation on the effective, local use of EG in SVT.

Topics: Drug Combinations; Escin; Female; Fibrinolytic Agents; Heparin; Humans; Male; Middle Aged; Phospholipids; Varicose Veins; Venous Thrombosis

Topics: Adolescent; Adult; Aged; Clinical Trials as Topic; Delayed-Action Preparations; Double-Blind Method; Escin; Female; Hemodynamics; Humans; Male; Middle Aged; Placebos; Plant Extracts; Saponins; Varicose Veins; Venous Insufficiency

Eight prospective, controlled, randomised studies on the incidence of postoperative thrombosis in gynaecological patients receiving various drugs for prevention of thromboembolism are analysed. In all patients diagnosis had been established by objective means. The rate of thrombosis in patients without drug prophylaxis has been found to vary between 14 and 29%. Infusions of dextran as well as administration of low-dose subcutaneous heparin significantly reduce the incidence of deep vein thrombosis, even as compared to postoperative oral anticoagulation with cumarins. No difference has been found between dextran and oral anticoagulants, when cumarin adminstration was started before operation, nor between dextran and heparin. Aescin did not show any prophylactic effect. High age, severe leg-vein varicosis as well as surgery for malignant disease increase the risk of thrombosis. No significant influence of overweight, previous deep venous thrombosis, epidural anaesthesia or vaginal operation as compared to abdominal approach could be demonstrated. There are no properly controlled, prospective, randomised studies on the incidence of postoperative fatal pulmonary embolism as influenced by drugs in gynaecological surgery.

Topics: Age Factors; Anesthesia; Dextrans; Escin; Female; Genital Diseases, Female; Heparin; Humans; Obesity; Postoperative Complications; Thromboembolism; Thrombophlebitis; Varicose Veins

Topics: Clinical Trials as Topic; Drug Combinations; Drug Evaluation; Escin; Flavonoids; Hesperidin; Humans; Phosphatidylcholines; Placebos; Saponins; Varicose Veins

Topics: Clinical Trials as Topic; Drug Combinations; Drug Evaluation; Escin; Flavonoids; Hesperidin; Humans; Phosphatidylcholines; Saponins; Varicose Veins

Topics: Adult; Aged; Clinical Trials as Topic; Delayed-Action Preparations; Drug Combinations; Escin; Female; Humans; Hydroxyethylrutoside; Male; Middle Aged; Nylidrin; Pyridoxine; Thiamine; Varicose Veins

Saponosides (horse chestnut seed extract, escin) and flavonoids (diosmin, Daflon 500, Servier, France) exhibit venotonic properties that have been utilized in treatment of varicose veins. However, the cellular mechanisms underlying the venotonic properties of escin and diosmin are unclear. Because Ca(2+) is a major regulator of venous smooth muscle (VSM) function, we tested the hypothesis that escin and diosmin promote Ca(2+)-dependent venous contraction.. Rings of inferior vena cava (IVC) from male rats were suspended in a tissue bath for measurement of isometric contraction. Following control contraction to 96 mM KCl, the effects of escin and diosmin (10(-10) to 10(-4) M) on vein contraction were measured. To test the role of intracellular Ca(2+) release, the vein response to escin and diosmin was measured in Ca(2+)-free (2mM EGTA) Krebs. To test for Ca(2+)-dependent effects, IVC segments were pretreated with escin or diosmin (10(-4) M) in 0 Ca(2+) Krebs, then extracellular CaCl(2) (0.1, 0.3, 0.6, 1, 2.5 mM) was added and the [Ca(2+)](e)-contraction relationship was constructed. To test for synergistic effects of diosmin, IVC segments were pretreated with diosmin (10(-4) M), then stimulated with KCl (16-96 mM) or escin (10(-10) to 10(-4) M) and vein contraction was measured. Contraction data were presented as mg/mg tissue (means ± SEM).. In IVC segments incubated in normal Krebs (2.5 mM Ca(2+)), escin caused concentration-dependent contraction (max 104.3 ± 19.6 at 10(-4) M). Escin-induced contraction was not a rigor state, because after washing with Krebs, the veins returned to a relaxed state. In Ca(2+)-free Krebs, there was essentially no contraction to escin. In escin-treated veins incubated in 0 Ca(2+) Krebs, stepwise addition of extracellular CaCl(2) caused corresponding increases in contraction (max 80.0 ± 11.1 at 2.5 mM). In the absence of escin, the α-adrenergic agonist phenylephrine (PHE, 10(-5) M), angiotensin II (AngII, 10(-6) M), and membrane depolarization by KCl (96 mM) caused significant contraction (122.5 ± 45.1, 114.2 ± 12.2 and 221.7 ± 35.4, respectively). In IVC segments pretreated with escin (10(-4) M), the contractile response to PHE (9.7 ± 2.6), AngII (36.0 ± 9.1), and KCl (82.3 ± 10.2) was significantly reduced. Diosmin (10(-4) M) caused small contractions in normal Krebs (11.7 ± 1.9) and Ca(2+)-free Krebs (4.2 ± 2.2). In diosmin-treated veins incubated in 0 Ca(2+) Krebs, addition of extracellular CaCl(2) caused minimal contraction. Diosmin did not enhance the IVC contraction to PHE, AngII, or escin, but enhanced the contractile response to KCl (24-51 mM).. In rat IVC, escin induces extracellular Ca(2+)-dependent contraction, but disrupts α-adrenergic and AT(1)R receptor-mediated pathways and depolarization-induced contraction. The initial venotonic benefits of escin may be offset by disruption of vein response to endogenous venoconstrictors, limiting its long-term therapeutic benefits in varicose veins. Diosmin does not cause venous contraction or potentiate the venotonic effects of endogenous venoconstrictors or escin ex vivo, and its use as venotonic may need to be further evaluated.

Topics: Adrenergic alpha-1 Receptor Agonists; Angiotensin II; Animals; Calcium Signaling; Diosmin; Dose-Response Relationship, Drug; Escin; In Vitro Techniques; Male; Membrane Potentials; Muscle, Smooth, Vascular; Phenylephrine; Potassium Chloride; Rats; Rats, Sprague-Dawley; Receptor, Angiotensin, Type 1; Receptors, Adrenergic, alpha-1; Varicose Veins; Vasoconstriction; Vasoconstrictor Agents; Vena Cava, Inferior

The triterpene saponin escin is the active component of the extract of seeds of Aesculus hippocastanum used in the treatment of chronic venous insufficiency. Escin is also used experimentally to increase membrane permeability in isolated cells. Since endothelial dysfunction is postulated to be involved in venous insufficiency, the possible endothelium-protectant effect of escin was explored in rat aortic rings, a model widely used to study such effects with cardiovascular agents. Escin enhanced endothelium-dependent relaxation induced by acetylcholine when such relaxation had been reduced by exposure to the superoxide ion generator pyrogallol. This effect was attributed to enhanced nitric oxide production by endothelial nitric oxide synthase, a calcium-dependent enzyme, activated by the increased endothelial cell permeability to calcium induced by escin. Another effect of escin thought to contribute to its therapeutic activity is its ability to produce venous contraction. The compound was found to induce concentration-related contraction also in rat aortic rings. This response was partially inhibited by removal of the endothelium or by preincubation with indomethacin, and was completely abolished by incubation in a calcium-free perfusion fluid. Contraction was considered to be due mainly to the aforementioned effect on calcium permeability, with some mediation by release of endothelial vasoconstrictor prostanoids. It was concluded that, in rat aorta, escin possesses an endothelium-protectant action and a direct contractile effect. The former could contribute to its beneficial effect in the treatment of venous insufficiency, while the latter could constitute a limiting side effect.

Topics: Animals; Aorta, Thoracic; Dose-Response Relationship, Drug; Endothelium, Vascular; Escin; In Vitro Techniques; Male; Nitric Oxide Synthase Type III; Protective Agents; Rats; Varicose Veins; Vasoconstriction

To test in vitro the constrictor and relaxation responsiveness of variously diseased segments of human saphenous vein from patients with varicose vein disease.. The vein segments were derived (i) from the inguinal saphenous vein (valvularly incompetent and slightly dilated; tissue A); (ii) from the distal end of the lower leg just above the medial ankle (competent; tissue B); (iii) from a tributary to the long saphenous vein just below the knee (dilated, incompetent and overtly varicose; tissue C). The contractile responses were tested with phenylephrine (an alpha-adrenergic receptor agonist) and aescin, a clinically used phlebotonic drug derived from horse chestnut extract. Relaxant responses were tested with acetylcholine and sodium nitroprusside.. Both contractile agents contracted vein segments from the inguinal and ankle area with similar potency and efficacy, but were virtually without effect in the overtly varicose segments from the calf. EC50 values (molar concentration of the agonist that produces 50% of the maximum effect) in tissues A and B were 2.9 +/- 0.3 and 2.5 +/- 0.5 micromol l(-1) (phenylephrine) and 9.4 +/- 1.0 and 15.9 +/- 2.5 micromol l(-1) (aescin); the corresponding maximum effects (maximum effect, percent of KCl-induced contraction) were 76 +/- 3 and 70 +/- 4% (phenylephrine) and 70 +/- 2 and 71 +/- 3% (aescin) (P = NS in both cases for A vs B). In tissue C, the maximum effects were 5 +/- 5% (phenylephrine) and 10 +/- 7% (aescin) of KCl-induced contraction (not significantly different from zero). Acetylcholine-induced relaxation was similar for vein segments from locations A and B, whereas sodium nitroprusside was more effective in tissue B than A.. These findings support the notion that abnormalities within the venous wall affect venous smooth muscle contractility. Since competent and incompetent clinically normal vessels show normal contractile responses, whereas varicose vessels are not responsive to vasoactive drugs, it is likely that pharmacological treatment regimens are effective in early, but not in late stages of the disease.

Topics: Acetylcholine; Dose-Response Relationship, Drug; Escin; Female; Humans; Middle Aged; Muscle, Smooth, Vascular; Nitroprusside; Phenylephrine; Saphenous Vein; Varicose Veins; Vasoconstrictor Agents; Vasodilator Agents

Topics: Acute Disease; Adult; Drug Combinations; Drug Evaluation; Escin; Female; Gels; Heparin; Humans; Male; Middle Aged; Phospholipids; Postoperative Care; Postphlebitic Syndrome; Thrombophlebitis; Varicose Veins

Topics: Drug Combinations; Escin; Hesperidin; Humans; Methods; Phosphatidylcholines; Sclerosing Solutions; Telangiectasis; Varicose Veins

Topics: Drug Combinations; Drug Evaluation; Escin; Flavonoids; Hesperidin; Humans; Leg; Light; Phosphatidylcholines; Plethysmography; Postphlebitic Syndrome; Saponins; Varicose Veins; Venous Insufficiency

Topics: Administration, Oral; Administration, Topical; Drug Combinations; Escin; Flavonoids; Hesperidin; Humans; Phosphatidylcholines; Plethysmography; Saponins; Varicose Veins; Vasoconstriction; Veins

Topics: Acetylglucosaminidase; Arylsulfatases; Drug Combinations; Escin; Glucuronidase; Heparin; Hexosaminidases; Humans; Salicylates; Saponins; Sulfatases; Varicose Veins

Topics: Adult; Drug Combinations; Escin; Female; Humans; Lysosomes; Male; Plant Extracts; Saponins; Varicose Veins

Topics: Blood Flow Velocity; Blood Viscosity; Drug Combinations; Escin; Heparin; Humans; Rheology; Salicylates; Saponins; Varicose Veins

Topics: Adult; Drug Evaluation; Escin; Female; Heparin; Humans; Leg; Male; Middle Aged; Phlebitis; Phosphatidylcholines; Rutin; Saponins; Thermography; Thrombosis; Varicose Veins; Vascular Diseases

Topics: Adult; Aged; Delayed-Action Preparations; Drug Combinations; Escin; Female; Flavonoids; Humans; Male; Middle Aged; Saponins; Silymarin; Varicose Veins

Topics: Drug Combinations; Edema; Escin; Heparin; Humans; Leg; Rutin; Saponins; Thrombophlebitis; Varicose Veins; Venous Insufficiency

Topics: Drug Evaluation; Escin; Female; Humans; Male; Phosphatidylcholines; Rutin; Saponins; Thrombophlebitis; Varicose Veins; Venous Insufficiency

Topics: Blood Circulation; Drug Combinations; Escin; Female; Humans; Phlebitis; Phosphatidylcholines; Rutin; Saponins; Varicose Veins

Controlled experiments confirmed the therapeutic usefulness in gynecology of a phlebokinetic drug, in which EPL (polyunsaturated phosphatidylcholine) was combined with escine and rutine. The drug is particularly recommended for the prophylaxis and treatment of vein disorders caused by oral contraceptives. A total of 75 patients were treated with the drug (Essaven), in addition to the usual treatment (such as anticoagulants), while 75 controls received the usual treatment only. Results were excellent in cases of varicose veins, where the symptoms were eliminated in almost all cases. In cases of phlebitis and thrombophlebitis, the response was less univocal, but a definite improvement was evident in a good number of cases treated with Essaven; the drug also favored the return to normal conditions after thrombophlebitis attacks, reducing the duration of their painful aftereffects. The drug can be used daily for very long periods without side effects. It can also be used safely during pregnancy, without adverse effects on the fetus and on delivery. It is regarded as ideal to avoid the side effects of contraceptives on the venous system.

Topics: Adult; Aged; Contraceptives, Oral; Escin; Female; Humans; Phlebitis; Phospholipids; Pregnancy; Rutin; Saponins; Varicose Veins

Topics: Aesculus; Capillary Permeability; Escin; Flavonoids; Rats; Saponins; Thrombophlebitis; Varicose Veins

Topics: Aesculus; Erysipelas; Escin; Esophageal and Gastric Varices; Humans; Kidney Diseases; Leg Ulcer; Myocarditis; Thrombophlebitis; Thrombosis; Varicose Veins

Topics: Aesculus; Drug Combinations; Escin; Flavones; Flavonoids; Humans; Phospholipids; Thrombophlebitis; Thrombosis; Varicose Veins

Topics: Drug Combinations; Escin; Humans; Leg; Plant Extracts; Plants; Varicose Veins