Rabbit sciatic nerve fascicle and 'endoneurial' preparations for in vitro studies of peripheral nerve glucose metabolism.
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Adenosine Triphosphate↗
Biomedical subjects
D A Greene
Publications and source records attributed to D A Greene.
In vitro studies of the substrates for energy production and the effects of insulin on glucose utilization in the neural components of peripheral nerve.
An "endoneurial" preparation from a rabbit tibial nerve fascicle was used to study the ability of peripheral nerve axons and Schwann cells to derive their composite energy requirements from glucose, D-beta-hydroxybutyrate, or albumin-bound palmitate, and the effects of insulin in vitro on their composite glucose utilization. Samples incubated with 5 mM glucose for 2 h maintained a stable O2 uptake and P-creatine and ATP concentrations, and they exhibited a slight increase in P-creatine/creatine ratio (the electron microscopic appearance of the preparation was previously shown to be unaltered under these conditions). The rate of glucose oxidation required to account for the O2 uptake accounted for 61% of the glucose uptake. In samples incubated without substrate for 2 h, a marked fall in tissue glucose was associated with a 50% decrease in O2 uptake and with decreases in P-creatine, ATP, and in the P-creatine/creating ratio. In medium lacking glucose but containing 5 mM DL-beta-hydroxybutyrate, a stable rate of D-beta-hydroxybutyrate uptake was observed, and acetoacetate production accounted for only a small fraction; significant decreases in O2 uptake or ATP were prevented, and, although P-creatinde and the P-creatine/creatine ratio fell, they remained significantly higher than after incubation without substrate. An efficient blood-nerve barrier to albumin is known to exist. Medium containing albumin-bound palmitate with molar ratios or palmitate/albumin of 1 or 2 (highest FFA concentration, 1.32 meq/L) failed to prevent decreases in P-creatine, ATP, and in the P-creatine/creatine ratio during incubations without glucose; the associated O2 uptakes suggested that the tissue is susceptible to respiratory uncoupling and depression son exposure to albumin-blund palmitate as compared with non-neural tissue. Insulin (100 or 1000 microU/ml) had no detectable effects on glucose utilization in the endoneurial preparation during 2-h incubations with 5 mM glucose or (U-14C) glucose. In contrast, in epineurial tissue from rabbit sciatic nerve, insulin (100 micronU/ml) increased (U-14C) glucose incorporation into CO2 and total lipid. The neural components of peripheral nerve are probably dependent on glucose as their major substrate for energy production and respiration under most physiologic conditions in which elevated plasma ketone body concentrations are absent; their composite glucose utilization is not subject to acute, direct regulation by insulin in concentrations that might reasonably be derived from plasma insulin of pancreatic origin.
Adenosine Triphosphate↗
The complications of diabetes mellitus.
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Adult↗
An alteration in internodal myelin membrane structure in large sciatic nerve fibres in rats with acute streptozotocin diabetes and impaired nerve conduction velocity.
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Animals↗
Unusual echocardiographic manifestation of pericardial effusion.
Echocardiographic and sector scanning examinations were performed in a patient with pericardial effusion. In addition to the demonstration of fluid posterior to the left ventricle and anterior to the right ventricle, as in most significant pericardial effusions, there was an echo-free space representing fluid recorded posterior to the left atrium. Several possible explanations of this finding are offered.
Adult↗
Diabetic polyneuropathy: the importance of insulin deficiency, hyperglycemia and alterations in myoinositol metabolism in its pathogenesis.
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Acute Disease↗
Congenital complete tracheal rings. Report of a case.
An unusual congenital tracheal anomaly is described. Complete (closed) tracheal rings, occupying the entire length of the trachea, have seldom been reported. Most affected patients succumb to respiratory infections in early infancy. Diagnosis of this anomaly is difficult during life, but radiographic and endoscopic examinations may be revealing. There is no known definitive treatment, although the airway may be managed long enough for body growth to relieve the obstruction. This rare anomaly should be considered in those cases of intermittent respiratory obstruction that are not associated with other more common causes of stridor.
Humans↗
Localized cervical lymphadenopathy induced by diphenylhydantoin sodium.
Diphenylhydantoin sodium is a standard drug in the treatment of convulsive disorders. Numerous untoward reactions have been reported. Lymphadenopathy related to drug-induced hypersensitivity has occurred. A yound woman undergoing treatment for seizures developed a large, tender, localized neck mass, associated with trismus, spasmotic torticollis, fever, eosinophilia, and skin rash. She was thought to be suffering from a deep cervical fascial space abscess. Symptoms subsided rapidly after elimination of anticonvulsant medication.
Adult↗
Effects of insulin and dietary myoinositol on impaired peripheral motor nerve conduction velocity in acute streptozotocin diabetes.
The factors influencing the development of impaired sciatic motor nerve conduction velocity (MNCV) in acute experimental diabetes were examined. Decreased MNCV developed by the 14th day after streptozotocin administration but only in rats which became hyperglycemic. Insulin treatment, begun on day 3, failed to prevent imparied MNCV in diabetic rats in which improved or normal weight gain and a decreased degree of hyperglycemia was induced. However, insulin treatment prevented the development of impaired MNCV in a group of diabetic rats in which the tail vein plasma glucose concentration was never found to exceed 160 mg/dl during days 6 through 14, andin which the mean plus or minus SEM of the average plasma glucose concentration for each animal during the same period was 75 plus or minus 18 mg/dl. In normal rats fed diets containing 0.011% or 0.069% free myoinositol (a presumably normal range), sciatic nerve free myoinositol concentrations were 90- and 60-fold higher than those in plasma. On these diets the development of impaired MNCV in the diabetics was associated with a decrease in nerve free myoinositol as compared with nerves from normals fed the same diet, despite similar plasma levels in the normals and diabetics. Plasma and nerve free myoinositol increased with increasing dietary myoinositol content in both normals and diabetics, and nerve myoinositol content could be acutely increased by an i.p. myoinositol load. By supplementing the diets with 1.0% myoinositol, the difference in nerve myoinositol in normal and diabetic rats on day 14 was abolished; on this diet the development of impaired MNCV in the diabetics was moderated or totally prevented, despite persistent hyperglycemia and elevated nerve sorbitol and fructose concentrations. Insulin treatment that prevented impaired MNCV prevented a decrease in nerve myoinositol in diabetics. These studies suggest that insulin deficiency, and possibly hyperglycemia, are primary factors in the development of imparied MNCV in acute experimental diabetes. However, the development of impaired MNCV appears to be related in some manner to a derangement in the regulation of nerve free myoinositol content, which appears to be subject to modification by increases in plasma myoinositol concentration over a critical range.
Animals↗
Effects of aldose reductase inhibitors on the progression of nerve fiber damage in diabetic neuropathy.
Aldose reductase inhibitors improve nerve biochemistry, function, and structure in diabetic animals and increase nerve conduction in diabetic patients. Nevertheless, it has been difficult to demonstrate a benefit from these agents in patients with clinically overt diabetic neuropathy. Direct measurement of the nerve tissue penetration and biochemical and biological potency of these compounds is essential to fully understand and evaluate their effectiveness. Human sural nerve biopsies obtained from diabetic neuropathic patients undergoing treatment with an aldose reductase inhibitor revealed a reduction in intermediates of the polyol pathway. Specific morphologic lesions that correlate with the degree of clinical and electrophysiologic impairment also were identified. Morphologic evaluation of sural nerve biopsies obtained after aldose reductase inhibitor treatment suggests that these biochemically effective compounds ameliorate clinically relevant structural lesions in patients with diabetic neuropathy.
Aldehyde Reductase↗
Effect of hyperglycemia and the aldose reductase inhibitor tolrestat on sural nerve biochemistry and morphometry in advanced diabetic peripheral polyneuropathy. The Tolrestat Study Group.
Tolrestat is a well tolerated nonhydantoin aldose reductase inhibitor that has been reported to improve nerve conduction in diabetic animals and humans. Its effects on nerve biochemistry and structure have not been studied in patients with diabetic neuropathy. Patients with advanced diabetic neuropathy treated with long-term open-label tolrestat were randomly assigned to continuation on drug treatment or to placebo-controlled drug withdrawal for 12 months. At the end of this period, sural nerve biopsies were obtained for measurement of glucose, sorbitol, and fructose content, and for detailed morphometric analysis. Tolrestat ameliorated the glucose-mediated increase in sorbitol and fructose in sural nerve tissue. No statistically significant differences in nerve morphometry emerged between the two groups; however, both treatment groups exhibited increased nerve-fiber regeneration and normalization of axo-glial dysfunction and segmental demyelination following long-term tolrestat treatment. These findings are similar to those previously reported in a placebo-controlled sequential nerve biopsy study with the aldose reductase inhibitor sorbinil. Thus tolrestat is a biochemically effective aldose reductase inhibitor in human diabetic nerve with potential therapeutic efficacy for diabetic neuropathy.
Aldehyde Reductase↗
Components of variance for vibratory and thermal threshold testing in normal and diabetic subjects.
Quantitative sensory testing (QST) is commonly used in the assessment of diabetic neuropathy. However, little data are available on the reliability of tactile and thermal testing devices. Reproducibility of QST measures between centers has not been previously reported. This study was designed to validate QST testing procedures and determine if these devices are suitable for large scale multicenter clinical trials. Finger and toe vibratory (Vf, Vt) and thermal (Tf, Tt) thresholds were determined for ten normal individuals by a two-alternative forced-choice procedure using the Optacon Tactile Tester (OTT) and Thermal Sensitivity Tester (TST). Threshold measurements were reproducible between technologists and had a day-to-day coefficient of variation of Vf 20%, Vt 23%, Tf 41%, and Tt 95%. Thresholds were determined for 140 normal individuals at six centers. Mean threshold values between centers were not significantly different. Center-to-center coefficients of variation (CV) were Vf 44%, Vt 45%, Tf 47%, and Tt 87%. There was no significant difference in threshold measures with regard to sex, side studied, presence of calluses, or skin temperature. Vf thresholds significantly correlated with age (p < 0.01). There was no correlation between either vibratory or thermal thresholds in normal individuals, and nerve conduction velocities (NCV). Thermal and vibratory thresholds were determined for 98 diabetic patients. Diabetic subjects without clinical evidence of neuropathy were not significantly different from normal individuals, but diabetic patients with neuropathy had increased thresholds compared to normals (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Glucose-induced alterations in nerve metabolism: current perspective on the pathogenesis of diabetic neuropathy and future directions for research and therapy.
Recent animal and in vitro studies have identified several interrelated metabolic abnormalities in diabetic nerve that are attributable to elevated ambient glucose concentrations. In combination, these metabolic changes may induce a variety of biochemical and biophysical alterations in peripheral nerve that are highly relevant to the pathogenesis of diabetic neuropathy. This article reviews the current status of several of these metabolic defects and describes ways in which their interaction could lead to pathogenetically important changes in nerve metabolism, function, and structure. Areas of related future research are also discussed.
Animals↗
Insulinoma in a 94-year-old woman: long-term therapy with verapamil.
Several drugs can be used to control hypoglycemia caused by insulin-secreting pancreatic tumors but none are reliably efficacious or free of side effects. We report the case of a woman with an insulinoma who refused surgical intervention and was successfully treated with the Ca2+-channel blocker verapamil.
Adenoma, Islet Cell↗