Evaluation of the local effects of vitamin E (E-Mousse) on free radicals in diabetic microangiopathy: a randomized, controlled trial.

The aims of the study were to evaluate the short-term effects of a new thermosensitive, vitamin E (V-E) mousse on local free radicals (FR) and skin flux in diabetic microangiopathy. A group of 40 patients with diabetic microangiopathy was included. The variation in measurements of skin FR was evaluated by the D-Rom test. Subjects were between 45 and 65 years with type II diabetes and good metabolic control. E-mousse, a thermoactive preparation of acetate vitamin E (20%), was applied twice daily on the whole surface of the leg (below knee) and foot for 3 weeks. The contralateral leg was untreated acting as control. Subjects with age between 45 and 65 years with type II diabetes (diagnosed at least 5 years before) and good metabolic control (blood sugar < 180 mg/dL) were included after informed consent. Patients with uncontrolled diabetes, peripheral vascular disease, and severe lower limbs infections were excluded. Local free radicals (FR) and laser Doppler flux including the venoarteriolar response (VAR) were evaluated. The tolerability was evaluated by a semiquantitative score. Of the 40 included patients 34 completed the study. The 2 groups were comparable. At 3 weeks there was no decrease in FR in controls; the decrease in the treatment group was 45.3% (p < 0.05). Also in the treatment group RF decreased (p < 0.05) and the VARveno improved from an average of 21% to an average of 38% (p < 0.05). No significant variations were observed in the control group. The variation in symptomatic score was from a total value of 8 to 5 in the control group and from 8 to 1 in the treatment group (p < 0.02). Their tolerability was good. In conclusion local treatment with E-mousse for 3 weeks in diabetic microangiopathy improves skin microcirculation and the metabolic condition as shown by the decrease in FR.

Intermittent claudication in diabetics: treatment with exercise and pentoxifylline--a 6-month, controlled, randomized trial.

The aims of this study were to evaluate the effect of PXF (1600 mg daily) in diabetic patients with intermittent claudication. Of the 60 included patients, 53 completed the study (27 in the PXF group). There were seven dropouts. The groups were comparable for age, sex distribution, and total walking distance (TWD), and risk factors. There was an increase in TWD at 3 and 6 months in both groups (p<0.05) possibly due to exercise. However the increase (both absolute and percentage) in TWD was significantly larger in the PXF group. At 6 months, PXF produced a 292% increase in TWD (vs 180% produced by placebo) (p<0.02). The excess increase produced by PXF treatment was 112% at 6 months in comparison with placebo (p<0.02). Treatment was well tolerated. Between-group analysis favors PXF considering TWD, and results indicate good efficacy and tolerability.

Treatment of severe intermittent claudication with PGE1--a short-term vs a long-term infusion plan--a 20 week, European randomized trial--analysis of efficacy and costs.

The efficacy, safety, and cost of prostaglandin E1 (PGE1) in the treatment of severe intermittent claudication was studied by comparing a long-term treatment protocol (LTP) with a short-term treatment protocol (STP) in a randomized 20-week study. The study included 109 patients (96 completed the study) with an average total walking distance of 65.5 +/- 8 m (range 20-109). Phase 1 was a 2-week run-in phase (no treatment) for both protocols. In LTP, phase 2 was the main treatment phase. In the LTP, treatment was performed with 2-hour infusions (60 microg PGE1, 5 days each week for 4 weeks). In phase 3 (4-week interval period) PGE1 was administered twice a week (same dosage). In phase 4 (monitoring lasting 3 months, from week 9 to 20) no drugs were used. In STP, phase 2 treatment was performed in 2 days by a 2-hour infusion (1st day: morning 20 microg, afternoon 40 microg; 2nd day morning and afternoon 60 microg). The reduced dosage was used only at the first cycle (week 0) to evaluate reduced tolerability or side effects. Full dosage (60 microg b.i.d.) was used for all other cycles. The same cycle was repeated at the beginning of weeks 4, 8, and 12. The observation period was between weeks 12 and 20. A treadmill test was performed at inclusion, at the beginning of each phase, and at the end of the 20th week. A similar progressive physical training plan (based on walking) and a reduction in risk factors levels plan was used in both groups. Intention-to-treat analysis indicated an increase in walking distance, which improved at 4 weeks (101.5% in STP vs 78.3% in LTP), at 8 weeks (260.9% STP vs 107.3% LTP), and at 20 weeks (351% STP vs 242% LTP). Comparable increases in pain-free walking distance were observed in the two groups. No serious drug-related side effects were observed. Local, mild adverse reactions were seen in 7% of the treated subjects in the LTP and 5% in the STP. Average cost of LTP was approximately 6,588 ECU; for STP the average cost was approximately 1,881 ECU. The cost to achieve an improvement in walking distance of 1 m was 35.6 ECU with the LTP and 9.45 ECU with the STP (26% of the LTP cost; p<0.02). For an average 100% increase in walking distance the LTP cost was 1,937 ECU vs 550 ECU with STP (p<0.02). The cost of PGE1 (including infusion and operative costs) was 25% of the total cost for LTP (24.9% for STP). In summary, between-group-analysis favors STP, in terms of walking distance and costs. Results indicate good efficacy and tolerability of PGE1 treatment. With STP less time is spent in infusion and more can be spent in the exercise program. STP reduces costs, speeds up rehabilitation, and may be used in a larger number of nonspecialized units available to follow the protocol.

[Control of the progress of arteriosclerosis in high risk subjects treated with mesoglycan. Measuring the intima media]. / Controllo della progressione dell'arteriosclerosi in soggetti ad alto rischio trattati con mesoglicano. Misurazione dell'intima-media.

BACKGROUND: Noninvasive ultrasonic biopsy (UB) can be used to classify arteriosclerotic lesions and their progression in the carotid and femoral bifurcation. Also the evaluation of intima-media thickness (IMT) is useful to quantify the progression of early arteriosclerosis. METHODS: Two randomly selected groups of asymptomatic subjects were included in a 18 month, open study. One group was treated with oral mesoglycan (200 mg/day) and one group was followed-up as control. The two groups were comparable for age and sex distribution. RESULTS: The average UB score was 14.4 +/- 5 in the treatment group and 14.3 +/- 8 in the control group. After 18 months the UB score was 15.7 +/- 4 in the treatment and 16.2 +/- 6 in the control group. The average increase in IMT in 18 months in the treatment group was 0.016 mm equivalent to 0.0106 mm per year. In the control group the average increase was 0.119 equivalent to 0.0793 per year. Therefore the increase in IMT was 7.48 times greater in the control group. These differences were significant (p < 0.05). Two drop-outs were recorded in the treatment group and 1 in the control group. CONCLUSIONS: In conclusion IMT measurements showed a decreased level of IMT progression in subjects under mesoglycan treatment. These results need to be confirmed by a larger randomised study.

Fibrinolytic enhancement in diabetic microangiopathy with defibrotide.

Skin microcirculation was evaluated in 117 patients with diabetic microangiopathy over a period of six months. They were divided into two groups. Group 1 (64 patients) was treated with oral defibrotide, a new profibrinolytic drug, in association with diet and oral antidiabetic drugs. Group 2 (53 patients) was treated only with diet and antidiabetic agents. The microcirculation was studied by means of laser-Doppler flowmetry transcutaneous partial pressure of oxygen and carbon dioxide pressure measurements, and evaluation of capillary filtration. After six months, patients in group 1 improved their microcirculatory parameters in association with an improvement in signs and symptoms. Moreover, 30 patients in group 1 and 36 in group 2 were followed up for eighteen months, and the authors observed that the deterioration of the microcirculatory parameters was significantly slowed in diabetics treated with defibrotide. A decrease in plasma fibrinogen during defibrotide treatment was observed in all treated patients in association with an increased fibrinolytic activity. In conclusion, it appears that defibrotide, enhancing fibrinolysis, improved the microcirculation in diabetics, preventing further, progressive deterioration.

Acute effects of hydroxyethylrutosides on capillary filtration in normal volunteers, patients with venous hypertension and in patients with diabetic microangiopathy (a dose comparison study).

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.

Elastic stockings in diabetic microangiopathy. Long-term clinical and microcirculatory evaluation.

One hundred and forty nine diabetics with microangiopathy were followed up for 4 years and studied by laser-Doppler flowmetry - measuring skin blood flux at rest [RF] and the venoarteriolar response [VAR]. Seventy four patients were advised to wear elastic stockings and 75 were kept as controls with the aim of evaluating the effects of stockings on the evolution of diabetic microangiopathy. After 4 years a significant deterioration was found in RF (increased) and VAR (decreased) in the untreated group in comparison with controls. Also 10 ulcerations developed in the untreated subjects (6.6% of limbs) in comparison with 3 ulcerations (2.02%) in the treated group. The difference was statistically significant. Therefore elastic stockings appear to be useful in diabetics with microangiopathy as they protect against the deterioration of the microcirculation and reduce the development of ulcerations.

[Progression of lesions of the arterial wall evaluated by ultrasonic biopsy in asymptomatic subjects and in diabetic and hyperlipidemic patients treated with bezafibrate. A 4-year follow-up]. / Progressione delle lesioni della parete arteriosa valutate con biopsia ultrasonica in soggetti asintomatici ed in diabetici ed iperlipidemici trattati con bezafibrato. Follow-up di 4 anni.

Non-invasive arterial ultrasonic biopsy (UB) has been used to evaluate and follow-up arterial wall changes in four years in asymptomatic subjects, hyperlipidemics and diabetics. Both groups of patients were randomised in a treatment group (bezafibrate 400 mg daily) and in a control group. The rate of progression (ROP) into the next higher UB class was recorded by UB scans repeated every six months. In diabetics and hyperlipidemics the rate of progression (ROP, namely the percent of patients progressing to the next class) was significantly higher than the ROP in the asymptomatic subjects. However in the bezafibrate group the ROP was significantly lower than that observed in the controls. As each UB class corresponds to different levels of risks of occult coronary ischemia and cardiovascular events in the following four years, the reduction of ROP with bezafibrate was an important and positive achievement.

[Efficacy of TTFCA in reducing the ratio between lymphatic and plasma protein concentration in lymphatic and postphlebitic edema]. / Efficacia di TTFCA nel ridurre il rapporto tra concentrazione linfatica e plasmatica di proteine nell'edema linfatico e postflebitico.

In subjects with lymphatic problems and postphlebitic edema there is a significant difference in the ratio between lymphatic and plasma concentration of protein (CL/CP) in the foot. Two groups of patients were studied (one group with lymphedema and the other with postphlebitic limbs) in order to assess the CL/CP ratio before and after TTCFA treatment (Centellase). The study confirmed the efficacy of treatment in achieving a significant reduction of CL/CP and distal edema.

[Vascular reactivity related to postural changes in diabetics]. / La reattività vascolare da variazioni posturali nei diabetici.

Resting skin flow (RF) and the venoarteriolar response (VAR) were studied in 40 patients with diabetic microangiopathy and neuropathy, in 40 diabetes with microangiopathy and in 30 normal subjects using laser-Doppler flowmetry. In patients with microangiopathy and neuropathy RF was increased and the VAR was impaired to a greater extent than in patients without neuropathy. We evaluated the microangiopathy index (VAR/RF) that was lower in diabetics without neuropathy and even lower in those with neuropathy than in normals We also evaluated the VAR with different postural changes.