Nerve electrophysiological changes in rats with early induced diabetes.

In rats with diabetes induced at weaning, pathological examinations have shown that the reduction of myelin thickness occurs earlier than axon size reduction. The aim of this study was to provide a detailed description of neurophysiological changes during nerve growth and maturation in rats with streptozotocin-induced diabetes in prepubertal stage. Five-day male Wistar rats received an injection of streptozotocin. Motor and sensory conduction velocities increased until 6.5 months in diabetic and control rats and at this age it became lower in diabetic rats. In diabetic rats, the amplitudes of the compound motor action potentials (CMAP) were lower by the 3 months and did not increase later. The amplitudes and areas of sensory action potentials (SNAP) increased until 9 months in both groups. SNAP duration decreased with ageing. Sensory peak 1 and peak 2 latencies became longer from 6.5 to 9 months in diabetic rats, with a longer latency difference between the 2 sensory peaks by 4 months. At 3 and 4 months of age, peak 1 and peak 2 latencies correlated with SNAP amplitude and duration in control rats but not in diabetic rats. In conclusion, in rats with early induced diabetes, the earliest electrophysiological impairments consist of lower CMAP amplitudes, and longer difference between latencies of sensory peaks 1 and 2. These sequential neurophysiological changes should be considered when testing new therapeutic approaches in diabetic neuropathy.

Effect of cerivastatin on peripheral capillary permeability to albumin and peripheral nerve function in diabetic rats.

OBJECTIVE: To examine the effect of cerivastatin on capillary permeability to albumin and peripheral nerve function in diabetic rats. ANIMALS: Diabetes was induced in male Wistar rats by i.p. injection of streptozotocin (STZ) at the age of 5 days. Forty diabetic rats were randomized in two groups: one treated by cerivastatin (diabetic treated group, DT) and the other untreated (diabetic untreated group, DU). The data were compared to a group of normal rats. MEASUREMENTS: The peripheral capillary filtration of albumin (CFA) was studied on a limb by a non-invasive isotopic method, and nerve electrophysiological measurements were performed. Rats were followed-up until 6 months. In group DU albumin retention (AR) increased by 3 months and lymphatic uptake of interstitial albumin was impaired at 6 months. None of these disorders was observed in group DT. Motor and sensory nerve conduction velocities (MNCV and SNCV) were significantly slower at 6 months in group DU but not in group DT as compared to control rats. The duration of the sensory nerve action potential (SNAP) was significantly longer in group DU than in control rats at 6 months whereas it did not differ in group DT and in control animals. CONCLUSIONS: This study shows that cerivastatin may prevent the peripheral increase in CFA and lymphatic dysfunction induced by diabetes. These beneficial effects on microcirculation may be involved in the prevention of nerve function deterioration. The underlying mechanisms are likely to be independent of a lipid-lowering effect, but their clarification needs further investigations.

In vivo sequential study of skeletal muscle capillary permeability in diabetic rats: effect of anthocyanosides.

Alterations in the capillary filtration of macromolecules are well documented in diabetic patients and experimental diabetes. Various flavonoids including anthocyanosides and ginkgo biloba extracts have been shown to be effective against experimentally induced capillary hyperfiltration. The aim of the present study was to test the effects of anthocyanosides on capillary filtration in diabetic rats. For this purpose, we have validated the use of our previously described in vivo method for measurement of the capillary filtration of albumin (CFA) in rats. Male Wistar rats with streptozotocin (STZ)-induced diabetes were randomized in 3 groups to receive either ginkgo biloba (group A), Vaccinium myrtillus (group B), or no treatment (group C). The isotopic test of CFA consisted of intravenously injecting 99mtechnetium-labeled albumin, inducing venous compression on a hindquarter, and measuring radioactivity externally on the limb before, during, and after removal of venous compression. After removal of the tourniquet, the radioactivity curve decreased. Interstitial albumin retention (AR) and the ratio of the amplitudes of the low- and high-frequency peaks (LF/HF ratio), an index of lymphatic function obtained by the fast Fourier transform of the last part of the radioactivity curve, were calculated. In STZ-treated animals, the isotopic test was performed at a mean age of 97 days (time 1) and after 6 weeks (time 2) and 12 weeks (time 3) of treatment, ie, 6 and 12 weeks after time 1. At time 1, AR was significantly higher in the 3 diabetic groups than in the control rats, without a significant difference between these groups. In group B, AR decreased significantly (P = .015) at times 2 and 3. In group C, AR increased significantly (P < .0005) from time 1 to time 3. In group A, AR increased slightly (NS) between time 1 and time 3. In groups A and C, the LF/HF ratio significantly increased with time (P < .0005) and the levels at time 3 were significantly higher versus control rats (P < .0001). In group B, the LF/HF ratio remained unchanged from time 1 to time 3 and similar to the values found in the control rats. In conclusion, these data show that (1) this new in vivo noninvasive method can be used to study CFA in skeletal muscle in diabetic rats, (2) it is reproducible and may be repeated over several months to evaluate spontaneous microcirculatory changes, and (3) anthocyanosides appear to be effective in preventing the increase in CFA and the failure of lymphatic uptake of interstitial albumin in diabetic animals.

Effect of pravastatin on erythrocyte rheological and biochemical properties in poorly controlled Type 2 diabetic patients.

AIMS: The rheological properties of erythrocytes are impaired in diabetes mellitus, especially because of changes in their membrane lipid composition. In hypercholesterolaemic patients, lowering plasma cholesterol is associated with an improvement of the erythrocyte rheological parameters. The aim of this study was to investigate the relationship between erythrocyte deformability, plasma lipids, lipid membrane composition and cytosolic cations in poorly controlled Type 2 diabetic patients and to test the effects of a cholesterol-lowering treatment on these parameters. METHODS: We compared 37 poorly controlled Type 2 diabetic patients with 26 controls. In 22 of the diabetic patients who showed an impairment in erythrocyte deformability (filtration index >10.5 on the Hanss' haemorheometer), a double-blind randomized trial compared the effect of the inhibitor of HMG CoA reductase pravastatin 20 mg per day for 4 months vs. placebo on the erythrocyte parameters. RESULTS: Compared with controls, diabetic patients had higher filtration index (FI), erythrocyte sodium and calcium contents and lower free cholesterol-phospholipids ratio in erythrocyte membranes. Erythrocyte sodium content correlated positively with the FI and the membrane free cholesterol-phospholipids ratio. In the pravastatin-treated group (11 patients), fibrinogen decreased significantly, FI reached a normal value (<10) in six patients. Four of the five other patients who still had abnormal FI after 4 months of treatment had either a high plasma triglycerides (> or =4.60 mmol/l) or a high plasma fibrinogen (> or =4 g/l) level at baseline. Only two of the 11 placebo-treated patients achieved a normal FI. CONCLUSION: These data suggest that in poorly controlled Type 2 diabetic patients there is a link between the chemical composition and the rheological properties of erythrocytes. Erythrocyte deformability may be improved by lowering plasma cholesterol with a statin.

Effects of a purified micronized flavonoid fraction on capillary filtration in diabetic patients.

The objective of the present study was to investigate the effects of a purified micronized flavonoid fraction (Daflon 500 mg) on the increased capillary filtration of albumin (CFA) which is an early change in the microcirculation of patients with diabetes. A placebo controlled trial lasting 30 to 42 days including two equal groups of 20 patients, following a 15-day initial placebo run-in phase. The CFA test employed consisted of injecting albumin labelled with technetium (99mTc) intravenously, applying a venous tourniquet to one arm, and counting the radioactivity on the ipselateral forearm using an external gamma camera. The disappearance of radioactivity was analysed by means of two parameters after the tourniquet had been released, i.e. albumin retention (AR) and the LF/HF index which indicates lymphatic function in interstitial protein clearance. All patients included exhibited an increase in these two indices before the initial placebo run-in phase and at the end of the run-in period. At the end of the treatment phase, AR had significantly decreased in the group treated by the flavonoid fraction (FF) by comparison with the placebo group, and had normalized in 65% of patients in the FF group, compared with 25% of patients in the placebo group (p = 0.010). The LF/HF index normalized in 55% of cases in the FF group, compared with no patients on placebo (p = 0.00001). This study suggests that the flavonoid fraction tested here can improve and even normalize capillary filtration of albumin in diabetic patients.