Statil-sensitive polyol formation in nerve of galactose-fed mice.

The sciatic nerve of diabetic C57BL/Ks mice did not accumulate either sorbitol or fructose despite elevated nerve glucose levels, nor did they show a depletion of free myo-inositol. Galactose feeding of both nondiabetic and diabetic mice for five days resulted in marked accumulations of dulcitol in nerve indicating polyol forming activity. Levels of myo-inositol showed small elevations in nerves of galactose-fed mice which reached significance when compared to diabetic mice fed the standard diet.

Studies on peripheral nerve and lens in long-term experimental diabetes: effects of the aldose reductase inhibitor statil.

This study determined the axonal transport of choline acetyltransferase (ChAT) activity and its content in several tissues in nondiabetic control rats and in four groups of rats with streptozotocin-induced diabetes of 6-months duration. Diabetic rats were either untreated, treated only with either the aldose reductase inhibitor Statil (Imperial Chemical Industries, Pharmaceuticals Division, Macclesfield, UK) or insulin, or were given the two in combination. Insulin treatment consisted of a single weekly injection of a long-acting insulin, a regime designed not to control the diabetes, but to provide regular respite from the catabolic dominance of uncontrolled diabetes.

Ganglioside treatment of streptozotocin-diabetic rats prevents defective axonal transport of 6-phosphofructokinase activity.

This study measured axonal transport of 6-phosphofructokinase (PFK) and aldolase activities in the sciatic nerves of rats with short-term streptozotocin-induced diabetes. The diabetic rats showed deficits in anterograde (69% of controls; p less than 0.001) and retrograde (33% of controls; p less than 0.

Deficient axonal transport of substance P in streptozocin-induced diabetic rats. Effects of sorbinil and insulin.

This study measured the accumulation of substance P-like immunoreactivity (SPLI) proximal and distal to 12-h constricting ligatures applied to rat sciatic nerves. There were three separate experiments, and the baseline for each consisted of control and age-matched rats with 3 wk of untreated streptozocin-induced diabetes. We compared the effects of twice-daily insulin treatment, daily sorbinil (25 mg.

The overstated risk of preoperative hypokalemia.

To examine the relation between preoperative hypokalemia and frequency of intraoperative arrhythmias, Holter monitoring was employed in 447 patients undergoing major cardiac or vascular operations, the group at greatest risk for life-threatening arrhythmias. Based on serum potassium levels measured immediately before surgery, 57% of patients were normokalemic (greater than or equal to 3.6 mEq/L), 34% hypokalemic (3.

Ganglioside treatment of diabetic rats; effects on nerve adenosine triphosphatase activity and motor nerve conduction velocity.

Ouabain-sensitive ATPase activity (expressed as nmol ADP produced/h/mg (wet) nerve +/- SEM) was measured in homogenates of sciatic nerve from control rats and rats with streptozotocin-induced diabetes of 8 wk duration. Nerves from diabetic rats showed activity (21.7 +/- 2.

Does galactose feeding provide a valid model of consequences of exaggerated polyol-pathway flux in peripheral nerve in experimental diabetes?

This study was designed to examine the effect of exaggerated polyol-pathway flux on sciatic nerve content of polyols, myo-inositol, and water. Rats with streptozocin-induced diabetes of 3- and 12-wk duration and nondiabetic rats fed for 5 days on a diet containing 20% galactose were employed initially. All three conditions showed marked elevation of nerve polyol content, combined with fructose accumulation in the diabetic rats.

Axonal transport and tissue contents of substance P in rats with long-term streptozotocin-diabetes. Effects of the aldose reductase inhibitor 'statil'.

This study examined the axonal transport of substance P-like immunoreactivity (SPLI) and its content in dorsal root ganglion, trigeminal ganglion, stomach and ileum of non-diabetic rats and two groups of rats with streptozotocin-induced diabetes of 9 months duration. One diabetic group received the aldose reductase inhibitor 'Statil' throughout the period of study. To reduce morbidity all diabetic animals were given twice-weekly injections of a long-acting insulin which restricted weight loss but did not prevent regular and severe hyperglycaemia.

Fast anterograde axonal transport of choline-containing lipids in rats with experimental diabetes.

This study was designed to measure the velocity of axonal transport of choline-containing lipids in sensory and motoneurones of control rats and rats with streptozotocin-induced diabetes of 3 weeks duration. An additional experiment was performed in which nerves from control and diabetic rats were maintained in vitro during the period between injection of isotope in the nerve cell body region and arrest of transport. This was done to preclude the effects of temperature differences between controls and diabetics.

Protecting the brachial plexus during median sternotomy.

Injury to the brachial plexus was prospectively assessed in 335 patients undergoing median sternotomy for cardiac operation. All patients were placed in the hand-up position (elbows elevated, arms abducted 90 degrees, and elbows flexed) after right internal jugular vein cannulation (23 cannulation attempts were bilateral). Twenty-eight patients had new upper extremity complaints after the operation, of whom 16 (4.

Opposite effects of diabetes and galactosaemia on adenosine triphosphatase activity in rat nervous tissue.

This study measured the ouabain-sensitive adenosine triphosphatase activity in sciatic nerve, lumbar dorsal root ganglia and superior cervical ganglia from control rats, rats with 8 weeks streptozotocin-induced diabetes and rats fed a diet containing 20% galactose for 8 weeks. Whilst the sciatic nerves of the diabetic rats showed a 42% reduction in ouabain-sensitive adenosine triphosphatase activity, the galactose-fed rats showed an increase of 124% (p less than 0.01 and p less than 0.

Reduced anterograde and retrograde accumulation of axonally transported phosphofructokinase in streptozotocin-diabetic rats: effects of insulin and the aldose reductase inhibitor 'Statil'.

This study examined anterograde and retrograde accumulation of axonally transported 6-phosphofructokinase activity, proximal and distal to sciatic nerve constrictions, in rats with streptozotocin-induced diabetes of 4 weeks' duration. There were deficits in accumulation on both sides of the constriction in untreated diabetic rats (proximal accumulation 66% of controls, p less than 0.05; distal accumulation 32% of controls, p less than 0.

Defects of axonal transport in experimental diabetes that are unrelated to the sorbitol pathway.

This study examined the effect of experimental diabetes on the anterograde and retrograde axonal transport of phosphofructokinase activity. Rats with streptozotocin-induced diabetes of 4 weeks duration showed phosphofructokinase activity accumulation deficits both proximal (53% and 65% in two separate experiments) and distal (80% and 70%) to 24-h sciatic nerve constrictions. There was no significant effect of diabetes on the phosphofructokinase activity per unit length in unconstricted sciatic nerve.

Anterograde and retrograde axonal transport of 6-phosphofructokinase activity in the rat sciatic nerve.

Optimal conditions for the measurement of phosphofructokinase activity in segments of rat sciatic nerve were established. It was found that maximal activity was obtained when the Triton X-100 concentration of the extraction buffer was 1% (v:v). Nerve segments could be stored at ?80 degrees C for at least 1 week without measurable loss of activity.

Neutrophil sorbitol production impairs oxidative killing in diabetes.

The mechanism whereby hyperglycaemia inhibits neutrophil function is unclear. We have examined neutrophil killing of Candida albicans in the presence of increased concentrations of glucose and galactose. Killing was abolished in 50 mmol/l glucose and 10 and 50 mmol/l galactose.

Fast anterograde axonal transport in wasted and non-wasted diabetic rats; effects of aldose reductase inhibition.

This study measured the velocity of the fast anterograde axonal transport of [3H]-proline-labelled proteins in sciatic motoneurones of rats with streptozotocin diabetes of 12 weeks duration and in age matched controls. Four groups of diabetic animals were studied. One of these groups remained untreated whilst 2 diabetic groups received a long-acting insulin twice weekly to limit body wasting, but to permit regular hyperglycaemia.

Studies of sorbinil on axonal transport in streptozotocin-diabetic rats.

Deficits of axonal transport in short-term experimental diabetes may be a consequence of increased sorbitol pathway flux and may contribute to the development of degenerative neuropathies. Therefore, we studied the effect of the aldose reductase inhibitor sorbinil on the axonal transport of choline acetyltransferase (ChAT) in the cholinergic neurons of the sciatic nerve of rats with short-term streptozotocin diabetes. In addition, to examine the extent of axonal transport deficits, we studied the axonal transport of choline containing lipids in sensory neurons of the sciatic nerve of similarly diabetic rats and the effects of sorbinil thereon.

Slow component-a of axonal transport, nerve myo-inositol, and aldose reductase inhibition in streptozocin-diabetic rats.

This study measured sugars and polyols, weight/unit length, and slow component-a of axonal transport (SCa) in dorsal root afferents of the sciatic nerves of control rats and rats with streptozocin (STZ)-induced diabetes of 4-wk duration. The effects of two treatments--aldose reductase inhibition [Statil ("Statil" is a trademark; the property of Imperial Chemical Industries PLC.) ICI 128436 at 25 mg/kg/day, p.

Prevention of defects of axonal transport in experimental diabetes by aldose reductase inhibitors.

Experiments on streptozotocin-diabetic rats have indicated that axonal transport of choline acetyltransferase is reduced in sciatic nerve. Treatment with an aldose reductase inhibitor both prevented and reversed this defect which was related to marked accumulations of sorbitol and fructose. Concurrent with these accumulations the content of myo-inositol in diabetic peripheral nerve is depleted.

Pattern-deficient forelimb regeneration in adult bullfrogs.

This study was designed to test the ability of adult bullfrogs (Rana catesbeiana) to regenerate forelimbs, both with and without various experimental treatments. Distal humerus-level forelimb amputations provided with additional deviated (sciatic) nerve and/or repeated soft-tissue injury exhibited considerable outgrowth. However, control sham-operated forelimbs also produced regenerates with comparable frequency, size, and morphological complexity.

Fast orthograde axonal transport in sciatic motoneurones and nerve temperature in streptozotocin-diabetic rats.

This study measured the velocity of fast orthograde axonal transport of incorporated 3H-proline in motoneurones of the sciatic nerve in control rats and in rats with streptozotocin-induced diabetes of 3 weeks duration. Sciatic nerve and abdominal cavity temperatures were monitored throughout the period of measurement of transport velocity, and the rats were warmed to minimise hypothermia at both sites. There was marked abdominal and sciatic nerve hypothermia immediately after operation, and this effect was more intense in diabetic rats than in control rats.

Prevention of defective axonal transport in streptozocin-diabetic rats by treatment with "Statil" (ICI 128436), an aldose reductase inhibitor.

This investigation examined the effect of treatment of streptozocin-diabetic rats with the aldose reductase inhibitor "Statil" (25 mg/kg/day p.o.) on axonal transport in cholinergic neurons of the sciatic and vagal nerves and on nerve polyol and sugar levels.

Motor nerve conduction velocity and nerve polyols in mice with short-term genetic or streptozotocin-induced diabetes.

This study examined the relation between sciatic motor nerve conduction velocity and sciatic nerve contents of sorbitol, fructose, and myo-inositol in diabetic mice. Two groups of spontaneously diabetic animals (age 12 to 14 weeks and age 20 weeks) were compared with age-matched controls. In another experiment 17-week-old nondiabetic mice (of the same strain) were administered streptozotocin to induce diabetes and were subject to similar measurements 3 weeks later; age-matched controls were studied concomitantly.

Reversal of deficits in axonal transport and nerve conduction velocity by treatment of streptozotocin-diabetic rats with myo-inositol.

This study examined the effects of myo-inositol treatment on the deficits of motor nerve conduction velocity and of axonal transport of choline acetyltransferase in rats with streptozotocin-induced diabetes. Motor nerve conduction velocity was measured in seven groups of male rats. Two groups formed nondiabetic controls; one survived for 3 and the other for 6 weeks, then motor nerve conduction velocity was again measured and the accumulation of choline acetyltransferase activity proximal to a 24-h sciatic nerve constriction was estimated.