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Query: UMLS:C0031117 (peripheral neuropathy)
 10,577 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetic neuropathy, a challenging contemporary problem, has a clinical prevalence of 60% problematic peripheral neuropathy occurs in about 20%. Recent concepts in aetiopathogenesis include the role of sorbitol excess and myoinositol depletion in causing deficient Na+/K+ ATPase activity. Sorbitol excess per se may result in intraneuronal oedema. Besides these metabolic hypotheses, theories on endoneurial microcapillary pathology and hypoxia have gained favour. Furthermore, a unifying concept of sorbitol excess with intraneuronal oedema leading to secondary vascular compromise has been suggested. A new research classification linking clinical and laboratory evaluation has been proposed which may serve to unify research results. Quantitative sensory testing, autonomic function testing and electrodiagnosis have been utilised to detect incipient diabetic neuropathy. The benefit of 'tight' glycaemic control has been objectively documented by using laboratory parameters. Oral myoinositol supplementation and gangliosides have produced marginal improvement. The role of intraneuronal oedema in the pathogenesis of diabetic neuropathy and its reversal by aldose reductase inhibitors holds out fresh promise for their use in prevention and treatment.
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PMID:Diabetic peripheral neuropathy. 130 35

Guinea pigs fed a diet low in zinc develop clinical signs of apparent neurological origin. The signs include abnormal posture and locomotion as well as hypersensitivity to touch. In this study, electrophysiological and biochemical measurements were made on sciatic nerves from zinc-deficient and repleted animals as well as on controls fed either ad libitum or restricted to maintain weight comparable to those consuming the deficient diet. Both in vivo and in vitro measurements showed decreased motor nerve conduction velocity (NCV) in nerves of deficient animals. A longitudinal study showed excellent correlation of NCV and severity of clinical signs. Nerves from zinc-deficient guinea pigs had decreased Na,K-ATPase activity, but the number of sodium channels, as determined by saxitoxin binding, was not affected. It was concluded that the clinical signs of neuropathy in zinc deficiency are associated with impaired NCV and decreased Na,K-ATPase activity of peripheral nerves. The zinc-deficient guinea pig provides a useful model to study the biochemical defect in a peripheral neuropathy.
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PMID:Zinc status and peripheral nerve function in guinea pigs. 216 49

Nerve conduction slowing, a hallmark of both experimental and human diabetic neuropathy, is improved or corrected by aldose reductase inhibitors such as sorbinil. Recent animal experiments attribute acutely reversible nerve conduction slowing in diabetes to a myo-inositol (MI)-related defect in the nerve Na-K-ATPase (which generates the transmembrane sodium and potassium potentials necessary for nerve impulse conduction and the sodium gradient necessary for sodium-dependent uptake of substrates). This MI-related abnormality in Na-K-ATPase function is currently viewed as a cyclic, metabolic defect involving sequential alteration of Na-dependent MI uptake, MI content, MI incorporation into membrane phospholipids, and phospholipid-dependent Na-K-ATPase function in peripheral nerve. Aldose reductase inhibitors have been shown to normalize both nerve MI content and nerve Na-K-ATPase activity. These observations suggest that the acute effects of aldose reductase inhibitors on nerve conduction in both diabetic animals and patients may be mediated by correction of an underlying MI-related nerve Na-K-ATPase defect. Furthermore, this sorbinil-corrected Na-K-ATPase defect in diabetic nerve may contribute to other biochemical, functional, and structural abnormalities present in patients with diabetic peripheral neuropathy.
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PMID:A sodium-pump defect in diabetic peripheral nerve corrected by sorbinil administration: relationship to myo-inositol metabolism and nerve conduction slowing. 242 Nov 35

Decreased sciatic nerve myo-inositol content and Na+-K+-ATPase activity have been associated with slowing of motor nerve conduction in the acutely diabetic rat and have been invoked as possible pathogenic factors in diabetic peripheral neuropathy. Aldose reductase inhibitors prevent these abnormalities in peripheral nerves of the streptozocin (STZ)-diabetic rat. Whether an analogous biochemical abnormality occurs in the autonomic nervous system and plays a role in the development of diabetic autonomic dysfunction is unknown. Therefore we examined the effect of 8 wk of untreated STZ diabetes and administration of 20 mg X kg-1 X day-1 of the aldose reductase inhibitor sorbinil on myo-inositol level and Na+-K+-ATPase activity in rat superior cervical ganglia. Both myo-inositol concentration and Na+-K+-ATPase activity were reduced in ganglia from untreated STZ-diabetic rats, and sorbinil administration prevented these abnormalities. Thus, a sorbinil-responsive metabolic defect involving myotional abnormalities in the somatic and autonomic nervous systems in diabetes.
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PMID:Decreased myo-inositol content and Na+-K+-ATPase activity in superior cervical ganglion of STZ-diabetic rat and prevention by aldose reductase inhibition. 301 4

Trembler mutant mice are affected by a peripheral neuropathy characterized by hypomyelination, demyelination, and Schwann cell proliferation. In adult mutants, supernumerary Schwann cells form membranous structures known as 'onion-bulb' formations. The activities of the Na+, K+-ATPase and of two ouabain-insensitive Mg2+-ATPases were investigated in sciatic nerves of young and adult mutants. The Na+, K+-ATPase activities were 92 and 76% of the control values in young and adult mutants, respectively. By immunoblot analysis, the alpha-subunit of the Na+, K+-ATPase had an identical apparent molecular weight in controls at both ages and in young mutants. In adult mutants, on the contrary, the alpha-subunit appeared smaller by about 2 kd, similar to that in kidney, indicating that the Na+, K+-ATPase was localized mainly on supernumerary Schwann cells. In addition, in the mutants, the developmental increase of both the mitochondrial and the nonmitochondrial Mg2+-ATPase was abnormally high. We suggest that the abnormal increase of the nonmitochondrial Mg2+-ATPase activity during development reflects an enrichment of that enzyme in 'onion-bulb' formations.
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PMID:Three ATPase activities have an abnormal developmental time course in trembler sciatic nerves. 303 62

Endoneurial sodium, potassium adenosine triphosphatase (Na+,K+-ATPase) and Mg2+-ATPase activities were determined in routine sural nerve biopsies from patients being evaluated for peripheral neuropathy. A significant reduction of endoneurial Na+,K+-ATPase and Mg2+-ATPase activities was shown in six sural nerve biopsies from patients with Tangier disease complicated by mononeuropathy multiplex or progressive axonal neuropathy. Peripheral nerve ATPase activities did not correlate with myelinated or unmyelinated nerve fiber densities in these biopsies. Other peripheral neuronal disorders with reduced endoneurial Na+,K+-ATPase and Mg2+-ATPase activities included severe vasculitic neuropathy, diabetic neuropathy, tomaculous neuropathy, and motoneuron disease. Such reduced levels of ATPase activity in peripheral nerve may relate to altered endoneurial lipid metabolism and impaired axoplasmic flow.
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PMID:Endoneurial ATPase activity in Tangier disease and other peripheral neuropathies. 615 83

Experimental diabetes in rodents is associated with diminished activity of sodium-potassium-adenosine triphosphatase (Na+ -K+ -ATPase) in the sciatic nerve, an abnormality that has been invoked as being factorial in the genesis of diabetic peripheral neuropathy. Whether a parallel metabolic abnormality occurs in the autonomic vagus nerve is unknown. To answer this question, adult male rats made diabetic with streptozotocin (45 mg/kg) and age-matched nondiabetic controls were killed at 1 and 3 months after induction of diabetes. The cervical vagi and sciatic nerves were excised, weighed, and homogenized, and Na+ -K+ -ATPase activities were determined. After 1 month, the diabetic animals showed a significantly reduced sciatic nerve Na+ -K+ -ATPase activity as compared with respective controls, whether expressed in micromoles per gram wet weight per hour (20.5 +/- 4.9 [mean +/- SEM] vs 61.6 +/- 13.0) or micromoles per milligram of protein per hour (0.77 +/- 0.21 vs 2.48 +/- 0.57, p < 0.05, diabetic vs control, respectively). Diabetic vagus nerve Na+ -K+ -ATPase activity was also diminished (40.6 +/- 6.9 mumol/gm wet weight per hour vs 63.2 +/- 9.7 mumol/gm wet weight per hour and 3.83 +/- 0.81 mumol/mg protein per hour vs 5.86 +/- 0.73 mumol/mg protein per hour), but the results did not reach statistical significance. After 3 months, diabetic sciatic nerve Na+ -K+ -ATPase activity was still significantly less than the control group value (16.89 +/- 3.91 mumol/mg wet weight per hour vs 38.9 +/- 4.24 mumol/gm wet weight per hour and 0.48 +/- 0.11 mumol/mg protein per hour vs 1.04 +/- 0.14 mumol/mg protein per hour; p < 0.05, diabetic vs control, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Impaired rodent vagal nerve sodium-potassium-ATPase activity in streptozotocin diabetes. 784 68

The rationale for these experiments is that administration of L-carnitine and/or short-chain acylcarnitines attenuates myocardial dysfunction 1) in hearts from diabetic animals (in which L-carnitine levels are decreased); 2) induced by ischemia-reperfusion in hearts from nondiabetic animals; and 3) in nondiabetic humans with ischemic heart disease. The objective of these studies was to investigate whether imbalances in carnitine metabolism play a role in the pathogenesis of diabetic peripheral neuropathy. The major findings in rats with streptozotocin-induced diabetes of 4-6 weeks duration were that 24-h urinary carnitine excretion was increased approximately twofold and L-carnitine levels were decreased in plasma (46%) and sciatic nerve endoneurium (31%). These changes in carnitine levels/excretion were associated with decreased caudal nerve conduction velocity (10-15%) and sciatic nerve changes in Na(+)-K(+)-ATPase activity (decreased 50%), Mg(2+)-ATPase (decreased 65%), 1,2-diacyl-sn-glycerol (DAG) (decreased 40%), vascular albumin permeation (increased 60%), and blood flow (increased 65%). Treatment with acetyl-L-carnitine normalized plasma and endoneurial L-carnitine levels and prevented all of these metabolic and functional changes except the increased blood flow, which was unaffected, and the reduction in DAG, which decreased another 40%. In conclusion, these observations 1) demonstrate a link between imbalances in carnitine metabolism and several metabolic and functional abnormalities associated with diabetic polyneuropathy and 2) indicate that decreased sciatic nerve endoneurial ATPase activity (ouabain-sensitive and insensitive) in this model of diabetes is associated with decreased DAG.
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PMID:Neural dysfunction and metabolic imbalances in diabetic rats. Prevention by acetyl-L-carnitine. 795 1

This study is an attempt to assess the role of dietary supplementation in the treatment and prevention of diabetic peripheral neuropathy. The authors developed an animal model system to study this problem. Animals given streptozotocin to induce a type I diabetic state showed elevated glucose levels and decreased body weight. Analysis of the sciatic nerve revealed a decrease in nerve conduction velocity and Na(+)-K(+)-ATPase activity. The activity of protein kinase C, another component of the nerve transmission process, was also affected by the diabetic state. The dietary intervention of polyunsaturated fatty acids seemed to revert some of these changes toward normal.
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PMID:Polyunsaturated fatty acid supplementation in peripheral neuropathy. 836 34

The aims of this study were to investigate the effect of aminoguanidine (AG) on slowing of motor nerve conduction velocity (MNCV) of the sciatic nerve in streptozocin-induced diabetic rats and to assess its mechanism of action. The MNCV of the sciatic nerve was measured electrophysiologically in diabetic rats treated with and without AG for 16 weeks. To elucidate the action of AG, morphological lesion and abnormality of polyol pathway metabolism in the nerve were examined and tissue levels of advanced glycosylation end-products (AGE) were determined as an indicator of AGE accumulation in tissue. Diabetic rats were treated with AG at three doses of 10, 25 and 50 mg/kg for 16 weeks. Myelinated fiber morphometry and nerve Na+,K(-)-ATPase activity were determined. The AGE levels in renal cortex were measured by a specific ELISA. Aminoguanidine dose-dependently ameliorated slowing of MNCV 16 weeks after the treatment without changing body weight or blood glucose levels. No difference in myelinated fiber morphometry or Na+,K(+)-ATPase activity with or without AG treatment was detected in diabetic rats. Diabetes increased the AGE level in the renal cortex by six times compared to non-diabetic rats, and AG reduced the rise in the AGE level by 40%. The MNCV was inversely correlated with the AGE levels. We conclude that improvement of conduction slowing by AG in experimental diabetes may be through decreasing the AGE level in the peripheral tissues. Aminoguanidine may have a therapeutic potential in controlling diabetic peripheral neuropathy.
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PMID:Slowing of peripheral motor nerve conduction was ameliorated by aminoguanidine in streptozocin-induced diabetic rats. 864 Feb 99


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