rutin and Diabetic-Angiopathies

This study was planned to demonstrate in a prospective, placebo-controlled, randomized study, whether HR (Paroven, Venoruton; 0-(beta-hydroxyethyl)-rutosides), is effective in improving the microcirculation in subjects with diabetic microangiopathy and neuropathy. Patients with severe diabetic microangiopathy, neuropathy and edema, patients with microangiopathy, without neuropathy, and 20 healthy subjects were included. Microangiopathy was defined by laser Doppler flowmetry and capillary filtration (rate of ankle swelling (RAS)). Inclusion criteria were: increase in resting flux (RF) and RAS, a decrease in venoarteriolar response (VAR), and alterations in flux increase with temperature. The 2 groups of patients and the control group were randomized in a treatment sub-group which received HR (1 g, twice daily for 6 months); those in the placebo group received similar treatment.. Groups were comparable; there were no drop-outs. There were no differences in the treatment and placebo groups at inclusion. Treatment was well tolerated; no adverse effects were reported. No variations were observed in healthy subjects at 6 months. In both groups of patients, significant decreases (P < 0.05) in RF and RAS were observed in the active treatment groups. The decrease in RAS was associated with a decrease in edema (P < 0.05) in both treatment groups. The decrease in RF and the increase in VAR were associated with a proportional decrease in RAS (P < 0.05). In patients without neuropathy, the variations in RF, VAR, and RAS were larger (P < 0.05) at 6 months. The variations in healthy subjects were limited and not significant.. The decrease in capillary filtration and edema with HR is associated with symptomatic improvement. The action on edema is beneficial for the evolution of neuropathy. The effects of HR on flux, RAS, and edema are important in early stages of microangiopathy to avoid progression to clinical stages.

Topics: Adult; Diabetic Angiopathies; Diabetic Neuropathies; Edema; Female; Humans; Hydroxyethylrutoside; Hypertension; Laser-Doppler Flowmetry; Male; Microcirculation; Middle Aged; Placebos; Skin Ulcer; Treatment Outcome; Vasoconstrictor Agents

The acute effects of hydroxyethylrutosides on capillary filtration were studied in 12 normal subjects, 25 patients with venous hypertension and 22 diabetics with microangiopathy. The two groups of patients randomly received a single oral dose (500 or 1000 mg) of hydroxyethylrutosides. A single dose of 500 mg was used for normal volunteers. In the following 6 hours capillary filtration was studied with straingauge plethysmography. The decrease in capillary filtration was evident within the first hour and was at its peak between the second and fourth hour. After 6 hours it was still significantly below baseline values in patients. The 1000 mg dose was significantly more effective in both groups of patients. This study confirms the efficacy of hydroxyethylrutosides in decreasing capillary filtration. It suggests that the effect of one dose lasts at least 6 hours and also that the higher dose is more effective.

Topics: Adult; Capillary Permeability; Carbon Dioxide; Diabetic Angiopathies; Dose-Response Relationship, Drug; Female; Humans; Hydroxyethylrutoside; Male; Middle Aged; Oxygen; Regional Blood Flow; Skin; Venous Insufficiency

This study analyzes the effect of chronic treatment with different antioxidants (N-acetyl-cysteine [NAC], taurine, a combination of NAC and taurine, and oxerutin) on long-term experimental diabetes induced by streptozotocin in rats. Glycoxidative damage was evaluated in the skin; glomerular structural changes were studied with morphometry and immunohistochemistry. Oxerutin treatment and the combined NAC plus taurine treatment resulted in reduced accumulation of collagen-linked fluorescence in skin in comparison with untreated diabetic rats. All treatments except taurine reduced glomerular accumulation of N(epsilon)-(carboxymethyl)lysine and protected against the increase in glomerular volume typical of diabetes; furthermore, the apoptosis rate was significantly decreased and the glomerular cell density was better preserved. Glycoxidative markers in the skin turned out to be good indicators of the glomerular condition. The findings that emerged from our study support the hypothesis that glomerular damage in diabetes can be prevented or at least attenuated by supplementation with specific antioxidants. Treatment with oxerutin and combined treatment with NAC plus taurine gave the most encouraging results, whereas the results of taurine-only treatment were either negligible or negative and therefore suggest caution in the use of this molecule in single-drug treatment courses.

Topics: Acetylcysteine; Animals; Anticoagulants; Blood Glucose; Collagen; Diabetes Mellitus, Experimental; Diabetic Angiopathies; Hydroxyethylrutoside; Kidney; Male; Rats; Rats, Wistar; Skin; Taurine; Time Factors

To evaluate in a group of seriously diseased patients with nonreconstructable chronic critical leg ischemia (CLI), treated by a combination of i.v. hydroxyethylrutosides (HR)* and oral anticoagulation (AC) by warfarin, the short-term effects on the cutaneous microvascular blood perfusion of the soles of feet and especially the long-term clinical outcome in terms of amputation and death.. A retrospective comparison between two groups of patients, HR + AC and a comparable reference group, fulfilling the same inclusion and exclusion criteria corresponding to the definition of CLI according to the Second European Consensus Document (1991). Clinical follow-up in both groups was made after 1, 3, 6, 12, and 24 months.. Patients were examined at university departments of clinical physiology with special interest in peripheral vascular disease, in cooperation with colleagues at university departments of surgery, internal medicine and dermatology of Karolinska Hospital, Södersjukhuset and Huddinge Hospital.. A total of seventy patients with CLI according to the definition of the Second European Consensus Document, 1991, ie, besides severe rest pain or ischemic lesions also a toe blood pressure < 30 mg Hg. Group with HR + anticoagulation (AC): 42 patients (19 diabetics, 23 nondiabetics). Reference group: 28 patients (18 diabetics, 10 nondiabetics). For distribution of age and toe blood pressure at baseline, see Table I.. Therapy group: besides ordinary standard therapy, daily HR infusions for a mean period of 3.6 weeks + oral anticoagulation continued to the end of the study at 24 months. A comparable reference group on the same basic therapy but without the combination HR + AC. PARAMETERS IN EVALUATION: Short-term parameters: clinical data, skin temperature, and fluorescein imaging. Long-term outcome: amputation or death.. Short-term and long-term results with HR + AC indicated that patients with severe CLI and very poor prognosis benefited in terms of survival and limb salvage from initial therapy with HR infusion combined with long-term oral anticoagulation. Results of this combined treatment seem at least comparable with those with i.v. prostacyclin analogies.

Topics: Administration, Oral; Aged; Amputation, Surgical; Anticoagulants; Arteriosclerosis; Blood Pressure; Cardiovascular Agents; Contrast Media; Diabetic Angiopathies; Drug Therapy, Combination; Fluorescein; Follow-Up Studies; Foot; Humans; Hydroxyethylrutoside; Infusions, Intravenous; Ischemia; Leg; Longitudinal Studies; Microcirculation; Prognosis; Retrospective Studies; Skin Temperature; Survival Rate; Treatment Outcome; Warfarin

Clinical and experimental evidence support the metabolic aetiology of diabetic microangiopathy. This paves the way for its management by transplantation of endocrine pancreas. In an informative article, the authors attempts to conceptualize their position concerning indications for pancreas transplantation and offer a review of their own experimental studies, a prerequisite before actual clinical application.

Topics: Animals; Coumarins; Diabetic Angiopathies; Diabetic Nephropathies; Dogs; Drug Combinations; Fluoresceins; Graft Rejection; Humans; Hydroxyethylrutoside; Islets of Langerhans Transplantation; Organomercury Compounds; Tetracycline

Topics: Adenosine Diphosphate; Animals; Diabetic Angiopathies; Diethylamines; Hydroxyethylrutoside; Male; Nitriles; Platelet Adhesiveness; Platelet Aggregation; Rats; Rutin