Biomedical subjects

M J Stevens

Publications and source records attributed to M J Stevens.

At least 19 recordsLinked to original sources

PubMed2006

Nicotinamide reverses neurological and neurovascular deficits in streptozotocin diabetic rats.

In diabetes, activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) is an important effector of oxidative-nitrosative injury, which contributes to the development of experimental diabetic peripheral neuropathy (DPN). However, the potential toxicity of complete PARP inhibition necessitates the utilization of weaker PARP inhibitors with additional therapeutic properties. Nicotinamide (vitamin B3) is a weak PARP inhibitor, antioxidant, and calcium modulator and can improve energy status and inhibit cell death in ischemic tissues. We report the dose-dependent effects of nicotinamide in an established model of early DPN. Control and streptozotocin-diabetic rats were treated with 200 to 400 mg/kg/day nicotinamide (i.p.) for 2 weeks after 2 weeks of untreated diabetes. Sciatic endoneurial nutritive blood flow was measured by microelectrode polarography and hydrogen clearance, and sciatic motor and hind-limb digital sensory nerve conduction velocities and thermal and mechanical algesia were measured by standard electrophysiological and behavioral tests. Malondialdehyde plus 4-hydroxyalkenal concentration in the sciatic nerve and amino acid-(4)-hydroxynonenal adduct and poly(ADP-ribosyl)ated protein expression in human Schwann cells were assessed by a colorimetric method with N-methyl-2-phenyl indole and Western blot analysis, respectively. Nicotinamide corrected increased sciatic nerve lipid peroxidation in concert with nerve perfusion deficits and dose-dependently attenuated nerve conduction slowing, as well as mechanical and thermal hyperalgesia. Nicotinamide (25 mM) prevented high (30 mM) glucose-induced overexpression of amino acid-(4)-hydroxynonenal adducts and poly(ADP-ribosyl)ated proteins in human Schwann cells. In conclusion, nicotinamide deserves consideration as an attractive, nontoxic therapy for the treatment of DPN.

Animals↗

PubMed2006

Early diabetes-induced biochemical changes in the retina: comparison of rat and mouse models.

AIMS/HYPOTHESIS: Recently, various transgenic and knock-out mouse models have become available for studying the pathogenesis of diabetic retinopathy. At the same time, diabetes-induced retinal changes in the wild-type mice remain poorly characterised. The present study compared retinal biochemical changes in rats and mice with similar (6-week) durations of streptozotocin-induced diabetes. MATERIALS AND METHODS: The experiments were performed on Wistar rats and C57Bl6/J mice. Retinal glucose, sorbitol, fructose, lactate, pyruvate, glutamate, alpha-ketoglutarate and ammonia were measured spectrofluorometrically by enzymatic methods. Vascular endothelial growth factor (VEGF) protein was assessed by ELISA, and poly(ADP-ribosyl)ation by immunohistochemistry and western blot analysis. Free mitochondrial and cytosolic NAD(+)/NADH ratios were calculated from the glutamate and lactate dehydrogenase systems. RESULTS: Retinal glucose concentrations were similarly increased in diabetic rats and mice, vs controls. Diabetic rats manifested approximately 26- and 5-fold accumulation of retinal sorbitol and fructose, respectively, whereas elevation of both metabolites in diabetic mice was quite modest. Correspondingly, diabetic rats had (1) increased retinal malondialdehyde plus 4-hydroxyalkenal concentrations, (2) reduced superoxide dismutase (SOD), glutathione peroxidase, glutathione reductase and glutathione transferase activities, (3) slightly increased poly(ADP-ribose) immunoreactivity and poly(ADP-ribosyl)ated protein abundance, and (4) VEGF protein overexpression. Diabetic mice lacked these changes. SOD activity was 21-fold higher in murine than in rat retinas (the difference increased to 54-fold under diabetic conditions), whereas other antioxidative enzyme activities were 3- to 10-fold lower. With the exception of catalase, the key antioxidant defence enzyme activities were increased, rather than reduced, in diabetic mice. Diabetic rats had decreased free mitochondrial and cytosolic NAD(+)/NADH ratios, consistent with retinal hypoxia, whereas both ratios remained in the normal range in diabetic mice. CONCLUSIONS/INTERPRETATION: Mice with short-term streptozotocin-induced diabetes lack many biochemical changes that are clearly manifest in the retina of streptozotocin-diabetic rats. This should be considered when selecting animal models for studying early retinal pathology associated with diabetes.

Animals↗

PubMed2006

Accelerated partial breast irradiation using interstitial high dose rate iridium brachytherapy: Early Australian experience and review of the literature.

Summary Accelerated partial breast irradiation (APBI) is an evolving new technique of adjuvant irradiation in selected women with early-stage breast cancer. We developed a pilot programme of APBI in 2000 and report end results in seven patients followed for a mean of 42.7 months (range 29-55 months). Good to excellent cosmesis and no loco-regional relapse or systemic metastases have occurred. The literature related to APBI is reviewed.

Aged↗

PubMed2004

Systematic study of the effect of disorder on nanotribology of self-assembled monolayers.

The adhesion and friction between pairs of ordered and disordered self-assembled monolayers on SiO2 are studied using molecular dynamics. The disorder is introduced by randomly removing chains from a well ordered crystalline substrate and by attaching chains to an amorphous substrate. The adhesion force between monolayers at a given separation increases monotonically with chain length at full coverage and with coverage for fixed chain length. Friction simulations are performed at shear velocities between 0.02-2 m/s at constant applied pressures between 200 and 600 MPa. Stick-slip motion is observed at full coverage but disappears with disorder. With random defects, the friction becomes insensitive to chain length, defect density, and substrate.

Journal Article↗

PubMed2004

Evaluation of orally active poly(ADP-ribose) polymerase inhibitor in streptozotocin-diabetic rat model of early peripheral neuropathy.

AIMS/HYPOTHESIS: Poly(ADP-ribose) polymerase activation depletes NAD+ and high-energy phosphates, activates protein kinase C, and affects gene expression in various tissues. This study was designed to characterise the effects of the potent, orally active poly(ADP-ribose) polymerase inhibitor PJ34 in the Wistar rat model of early diabetic neuropathy. METHODS: Control and streptozotocin-diabetic rats were maintained with or without PJ34 treatment (30 mg x kg(-1) x day(-1)) for two weeks, after two weeks without treatment. Endoneurial blood flow was assessed by hydrogen clearance; metabolites and high-energy phosphates were assayed by enzymatic spectrofluorometric methods; and poly(ADP-ribose) was detected by immunohistochemistry. RESULTS: Blood glucose concentrations were increased to a similar extent in untreated and PJ34-treated diabetic rats compared with controls. Intense poly(ADP-ribose) immunostaining was observed in the sciatic nerve of diabetic rats, but not in other groups. Final sciatic motor nerve conduction velocity and digital sensory nerve conduction velocity were reduced by 24% and 22% respectively in diabetic rats compared with controls (p<0.01 for both), and both were 98% corrected by PJ34 (p<0.01 vs diabetic group for both). In contrast, with PJ34 treatment, nerve blood flow showed a modest (17%) increase, and vascular conductance showed a tendency to increase. Free mitochondrial and cytosolic NAD+:NADH ratios, assessed from the glutamate and lactate dehydrogenase systems, phosphocreatine concentrations, and phosphocreatine:creatine ratios were decreased in diabetic rats and essentially normalised by PJ34. In both untreated and PJ34-treated diabetic rats, nerve glucose, sorbitol and fructose were increased to a similar extent. PJ34 did not affect any variables in control rats. CONCLUSIONS/INTERPRETATION: Short-term poly(ADP-ribose) polymerase inhibitor treatment reverses functional and metabolic abnormalities of early diabetic neuropathy. Complete normalisation of nerve blood flow is not required for correction of motor or sensory nerve conduction velocities, provided that a therapeutic agent can restore nerve energy state via direct action on Schwann cells.

Animals↗

PubMed2003

Treatment of localized prostate cancer using a combination of high dose rate Iridium-192 brachytherapy and external beam irradiation: initial Australian experience.

Combination high dose rate brachytherapy (HDRB) and external beam radiation therapy is technically and clinically feasible as definitive treatment for localized prostate cancer. We report the first large Australian experience using this technique of radiation dose escalation in 82 patients with intermediate- and high-risk disease. With a median follow up of 3 years (156 weeks), complications were low and overall prostate-specific antigen progression-free survival was 91% using the American Society for Therapeutic Radiology and Oncology consensus definition. The delivery of hypofractionated radiation through the HDRB component shortens overall treatment time and is both biologically and logistically advantageous. As a radiation boost strategy, HDRB is easy to learn and could be introduced into most facilities with brachytherapy capability.

Adenocarcinoma↗

PubMed2001

Surface-tethered chains entangled in a polymer melt: effects on adhesion dynamics.

The adhesion between a polymer melt and substrate is studied in the presence of chemically attached chains on the substrate surface. Extensive molecular dynamics simulations have been carried out to study the effect of temperature, tethered chain density (Sigma), tethered chain length (N(t)), and tensile pull velocity (v) on the adhesive failure mechanisms of pullout and/or scission of the tethered chains. We observe a crossover from pure chain pullout to chain scission as N(t) is increased. The value of N(t) for which this crossover begins approaches the bulk entanglement length N(e) as the temperature is lowered.

Journal Article↗

PubMed2001

Depletion of taurine in experimental diabetic neuropathy: implications for nerve metabolic, vascular, and functional deficits.

In diabetes, increased oxidative stress, disruption of signal transduction pathways, and endothelial dysfunction have been critically implicated in the pathogenesis of experimental diabetic neuropathy (EDN). The development of nerve conduction slowing in diabetes is accompanied by depletion of the beta-amino acid taurine. Since taurine functions as an antioxidant, calcium modulator, and vasodilator, taurine depletion may provide a pathogenetic link between nerve metabolic, vascular, and functional deficits complicating diabetes. The mechanism(s) of nerve taurine depletion, the localization of critical taurine deficits, and its pathophysiological significance in EDN are however unknown. This study explored the pathophysiological effects of selective nerve taurine replacement in streptozotocin-diabetic (STZ-D) rats. A polyclonal human taurine transporter (TT) antibody was also generated in order to determine potential loci of critical taurine depletion. Two weeks of STZ-D reduced sciatic motor nerve conduction velocity (NCV) by 23% (P < 0.01), decreased composite nerve blood flow by 38% (P < 0.01), and reduced nerve taurine content by 29% (P < 0.05). In STZ-D rats, a 1% taurine diet corrected nerve taurine depletion, prevented motor NCV slowing, and partially attenuated composite nerve blood flow deficits. After 6 weeks of STZ-D, a 1% taurine diet ameliorated motor NCV slowing and endoneurial nutritive blood flow deficits, prevented digital sensory NCV slowing, and reduced ouabain-sensitive nerve (Na,K)-ATPase activity. Immunohistochemical studies localized taurine and the TT to the vascular endothelium and Schwann cells of the sciatic nerve. In conclusion, taurine depletion in the vascular endothelium and Schwann cells of the sciatic nerve may contribute to the neurovascular and metabolic deficits in EDN.

Animals↗

PubMed2001

Taurine counteracts oxidative stress and nerve growth factor deficit in early experimental diabetic neuropathy.

Oxidative stress has a key role in the pathogenesis of diabetic complications. We have previously reported that taurine (T), which is known to counteract oxidative stress in tissues (lens, kidney, retina) of diabetic rats, attenuates nerve blood flow and conduction deficits in early experimental diabetic neuropathy (EDN). The purpose of this study was to evaluate whether dietary T supplementation counteracts oxidative stress and the nerve growth factor (NGF) deficit in the diabetic peripheral nerve. The experiments were performed in control rats and streptozotocin-diabetic rats fed standard or 1% T-supplemented diets for 6 weeks. All measurements were performed in the sciatic nerve. Malondialdehyde (MDA) plus 4-hydroxyalkenals (4-HA) were quantified with N-methyl-2-phenylindole. GSH, GSSG, dehydroascorbate (DHAA), and ascorbate (AA) were assayed spectrofluorometrically, T by reverse-phase HPLC, and NGF by ELISA. MDA plus 4-HA concentration (mean +/- SEM) was increased in diabetic rats (0.127 +/- 0.006 vs 0.053 +/- 0.003 micromol/g in controls, P < 0.01), and this increase was partially prevented by T (0.096 +/- 0.004, P < 0.01 vs untreated diabetic group). GSH levels were similarly decreased in diabetic rats treated with or without taurine vs controls. GSSG levels were similar in control and diabetic rats but were lower in diabetic rats treated with T (P < 0.05 vs controls). AA levels were decreased in diabetic rats (0.133 +/- 0.015 vs 0.219 +/- 0.023 micromol/g in controls, P < 0.05), and this deficit was prevented by T. DHAA/AA ratio was increased in diabetic rats vs controls (P < 0.05), and this increase was prevented by T. T levels were decreased in diabetic rats (2.7 +/- 0.16 vs 3.8 +/- 0.1 micromol/g in controls, P < 0.05) and were repleted by T supplementation (4.2 +/- 0.3). NGF levels were decreased in diabetic rats (2.35 +/- 0.20 vs 3.57 +/- 0.20 ng/g in controls, P < 0.01), and this decrease was attenuated by T treatment (3.16 +/- 0.28, P < 0.05 vs diabetic group). In conclusion, T counteracts oxidative stress and the NGF deficit in early EDN. Antioxidant effects of T in peripheral nerve are, at least in part, mediated through the ascorbate system of antioxidative defense. The findings are consistent with the important role for oxidative stress in impaired neurotrophic support in EDN.

Aldehydes↗

PubMed2001

Antioxidants attenuate early up regulation of retinal vascular endothelial growth factor in streptozotocin-diabetic rats.

AIMS/HYPOTHESIS: A strong positive correlation has been found between lipid peroxidation product and vascular endothelial growth factor concentrations in the vitreous of patients with proliferative diabetic retinopathy. To establish a causal relation between diabetes-associated enhanced oxidative stress and vascular endothelial growth factor production, we evaluated two antioxidants, DL-alpha-lipoic acid and taurine, on retinal vascular endothelial growth factor protein and mRNA expression and on parameters of oxidative stress in streptozotocin-diabetic rats. METHODS: Our experiments were on control rats and streptozotocin-diabetic rats with a 6-week duration of diabetes, treated with or without DL-alpha-lipoic acid (100 mg x kg(-1) x d(-1), i.p.) or taurine (1% in the diet) starting from induction of diabetes. Vascular endothelial growth factor protein in retinal homogenates was assessed by sandwich ELISA with an affinity-purified polyclonal antibody and vascular endothelial growth factor mRNA by ribonuclease protection assay. Retinal lipid peroxidation products i.e. malondialdehyde plus 4-hydroxyalkenals were quantified with N-methyl-2-phenylindole. Retinal reduced and oxidized glutathione, ascorbate, dehydroascorbate, and sorbitol pathway intermediates were measured spectrofluorometrically, and taurine by reverse-phase HPLC. RESULTS: Vascular endothelial growth factor protein concentration (means +/- SD) was increased in diabetic rats compared with control rats (33+/-7 vs 19+/-5 pg/mg total protein, p < 0.01) This increase was attenuated by taurine (26+/-8, p < 0.05) and prevented by DL-alpha-lipoic acid (21+/-4, p < 0.01). Vascular endothelial growth factor mRNA abundance was reduced by 1.4-fold in diabetic rats compared with control rats and this decrease was attenuated but not completely prevented by both antioxidants. Malondialdehyde plus 4-hydroxyalkenal concentration was increased in diabetic rats compared with control rats, and both antioxidants arrested accumulation of lipid peroxidation products. Taurine, reduced glutathione, oxidized glutathione, ascorbate, dehydroascorbate and sorbitol pathway intermediate concentrations as well as oxidized glutathione/reduced glutathione and dehydroascorbate/ascorbate ratios were similar in control and diabetic rats treated with or without taurine. CONCLUSION/INTERPRETATION: Oxidative stress is directly involved in up regulation of vascular endothelial growth factor protein in the retina during early diabetes.

Alternative Splicing↗

PubMed2001

Simple simulations of DNA condensation.

Molecular dynamics simulations of a simple, bead-spring model of semiflexible polyelectrolytes such as DNA are performed. All charges are explicitly treated. Starting from extended, noncondensed conformations, condensed structures form in the simulations with tetravalent or trivalent counterions. No condensates form or are stable for divalent counterions. The mechanism by which condensates form is described. Briefly, condensation occurs because electrostatic interactions dominate entropy, and the favored coulombic structure is a charge-ordered state. Condensation is a generic phenomenon and occurs for a variety of polyelectrolyte parameters. Toroids and rods are the condensate structures. Toroids form preferentially when the molecular stiffness is sufficiently strong.

Biophysical Phenomena↗

PubMed2001

What makes recovered-memory testimony compelling to jurors?

Little is known about how jurors arrive at verdicts in cases involving recovered memories of childhood sexual abuse. Study 1 investigated mock jurors' reactions to the recovered-memory testimony of an alleged victim when a therapist intervened with hypnosis, suggestion, or symptom management. When a therapist used hypnosis, jurors viewed the victim's recovered-memory testimony as particularly accurate and credible, and favored the victim in their verdicts. In Study 2, mock jurors were presented with a therapist who was sued for allegedly influencing a client's recall of false memories of abuse. In this case, however, jurors viewed therapists who used hypnosis or suggestion as more likely to have created false memories, more responsible for having caused harm, and less competent, and tended not to favor these therapists in their verdicts. We discuss these seemingly contradictory findings in terms of how culturally formed expectancies about hypnosis produce different causal explanations depending on the focus of a trial.

Adolescent↗

PubMed2001

Sex-role strain in alcoholic women.

We investigated sources of sex-role strain between alcoholic and non-alcoholic women. We compared alcoholic (n = 55) and non-alcoholic (n = 51) women on the presence of strain in their sex-role identity and strain between sex-role identity, attitudes, and behaviors in 1996. One source of sex-role strain for alcoholic women was the discrepancy between their perceived femininity when intoxicated versus when sober. A second source of strain for alcoholic women was the discrepancy between their traditionally feminine sex-role identity as well as attitudes toward marital, parental, and educational roles and their participation in male-valued activities. We offer suggestions for future research.

Adult↗

PubMed2001

New imaging techniques for cardiovascular autonomic neuropathy: a window on the heart.

Cardiovascular autonomic neuropathy (CAN) is a common complication of diabetes, which results in disabling clinical manifestations and may predispose to sudden cardiac death. Recently, direct scintigraphic assessment of cardiac sympathetic integrity has become possible with the introduction of radiolabeled analogues of norepinephrine, which are actively taken up by the sympathetic nerve terminals of the heart. This article reviews how these techniques have been utilized to improve understanding of CAN complicating diabetes. Quantitative scintigraphic assessment of cardiac sympathetic innervation heart is possible with either [123I]-metaiodobenzylguanidine (MIBG) and single photon emission computed tomography (SPECT) or [11C]-hydroxyephedrine (HED) and positron emission tomography (PET). Studies in diabetic patients have explored the sensitivity of these techniques to detect CAN, characterize the effects of glycemic control on the progression of CAN and evaluate the effects of CAN on myocardial electrophysiology, blood flow regulation and function. Deficits of left ventricular (LV) [123I]-MIBG and [11C]-HED retention have been identified in diabetic subjects without abnormalities on cardiovascular reflex testing consistent with increased sensitivity to detect CAN. Poor glycemic control results in the progression of LV tracer deficits, which can be prevented or reversed by the institution of near-euglycemia. Deficits begin distally in the LV and may extend proximally. Paradoxically, however, absolute HED retention is increased in the proximal segments of the severe CAN subjects consistent with regional "hyperinnervation." These regions also exhibit abnormal blood flow regulation. Impaired myocardial MIBG uptake correlates with altered LV diastolic filling and myocardial electrophysiological deficits and is predictive of sudden death. Scintigraphic studies have provided unique insights into the effects of diabetes on cardiac sympathetic integrity and the pathophysiological consequences of LV sympathetic dysinnervation. Future studies using complementary neurotransmitter analogues will allow different aspects of regional dysfunction to be characterized with the aim of developing therapeutic strategies to prevent or reverse CAN.

3-Iodobenzylguanidine↗

PubMed2001

Diabetes-induced changes in retinal NAD-redox status: pharmacological modulation and implications for pathogenesis of diabetic retinopathy.

Diabetes-induced changes in retinal metabolism and function have been linked to increased aldose reductase activity, hypoxia or 'pseudohypoxia' (increase in NADH/NAD+ attributed to increased sorbitol dehydrogenase activity). To address this controversy, we evaluated the effects of two vasoactive compounds, alpha(1)-adrenoceptor antagonist prazosin and antioxidant DL-alpha-lipoic acid, as well as sorbitol dehydrogenase inhibitor (SDI-157) and aldose reductase inhibitor (sorbinil) on retinal free mitochondrial and cytosolic NAD+/NADH ratios in streptozotocin-diabetic rats. Diabetes-induced decrease in mitochondrial and cytosolic NAD+/NADH ratios was completely or partially corrected by prazosin and DL-alpha-lipoic acid (despite the fact that prazosin did not affect and DL-alpha-lipoic acid even further increased sorbitol pathway activity) as well as by sorbinil, whereas SDI-157 was totally ineffective. Hypoxia-like metabolic changes in the diabetic retina originate from aldose reductase, but not sorbitol dehydrogenase activity.

Adrenergic alpha-Antagonists↗

PubMed2000

Evaluation of alpha(1)-adrenoceptor antagonist on diabetes-induced changes in peripheral nerve function, metabolism, and antioxidative defense.

The role for nerve blood flow (NBF) vs. other factors in motor nerve conduction (MNC) slowing in short-term diabetes was assessed by evaluating alpha(1)-adrenoceptor antagonist prazosin on NBF, MNC, as well as metabolic imbalances and oxidative stress in the neural tissue. Control and diabetic rats were treated with or without prazosin (5 mg.kg(-1).d(-1) for 3 wk). NBF was measured by hydrogen clearance. Both endoneurial vascular conductance and MNC velocity were decreased in diabetic rats vs. controls, and this decrease was prevented by prazosin. Free NAD(+):NADH ratios in mitochondrial cristae, matrix, and cytosol assessed by metabolite indicator method, as well as phosphocreatine levels and phosphocreatine/creatine ratios, were decreased in diabetic rats, and this reduction was ameliorated by prazosin. Neither diabetes-induced accumulation of two major glycation agents, glucose and fructose, as well as sorbitol and total malondialdehyde plus 4-hydroxyalkenals nor depletion of myo-inositol, GSH, and taurine or decrease in (Na/K)-ATP-ase activity were affected by prazosin. In conclusion, decreased NBF, but not metabolic imbalances or oxidative stress in the neural tissue, is a key mechanism of MNC slowing in short-term diabetes. Further experiments are needed to estimate whether preservation of NBF is sufficient for prevention of nerve dysfunction and morphological abnormalities in long-standing diabetes or whether the aforementioned metabolic imbalances closely associated with impaired neurotropism are of greater importance in advanced than in early diabetic neuropathy.

Adrenergic alpha-Antagonists↗

PubMed2000

Severe hypertension induced by the long-acting somatostatin analogue sandostatin LAR in a patient with diabetic autonomic neuropathy.

A 26-yr-old woman with type 1 diabetes and severe symptomatic autonomic neuropathy was treated with the long-acting somatostatin analogue Sandostatin LAR for intractable diarrhea. Her diarrhea had previously been successfully managed with three daily injections of octreotide without adverse consequences. She was given a single dose of Sandostatin LAR and within 2 weeks reported the development of increasingly frequent and severe headaches. Three weeks after the injection, she was admitted to hospital with severe hypertension, which eventually resolved with the administration of antihypertensive agents. No other underlying cause of the hypertension was discovered. Rechallenge of the patient with octreotide resulted in a transient hypertensive episode, which lasted 3 h. Severe hypertension, therefore, seems to be a possible adverse effect of treatment of diabetic diarrhea with somatostatin analogues, which should be used with great caution in subjects with severe autonomic dysfunction.

Adult↗

PubMed2000

Effects of DL-alpha-lipoic acid on peripheral nerve conduction, blood flow, energy metabolism, and oxidative stress in experimental diabetic neuropathy.

Experimental diabetic peripheral neuropathy (DPN) is marked by impaired nerve conduction velocity (NCV), reduced nerve blood flow (NBF), and a variety of metabolic abnormalities in peripheral nerve that have been variously ascribed to hyperglycemia, abnormal fatty acid metabolism, ischemic hypoxia, and/or oxidative stress. Some investigators propose that NCV slowing in experimental DPN can be explained entirely on the basis of nerve energy depletion secondary to reduced NBF. This article reports highly selective effects of administration of the antioxidant DL-alpha-lipoic acid (LA) to streptozotocin-injected diabetic rats. LA improved digital sensory but not sciatic-tibial motor NCV, corrected endoneurial nutritive but not composite NBF, increased the mitochondrial oxidative state without correcting nerve energy depletion, and enhanced the accumulation of polyol pathway intermediates without worsening myo-inositol or taurine depletion. These studies implicate oxidative stress as an important pathophysiological factor in experimental DPN. They reveal complex interrelationships among nerve perfusion, energy metabolism, osmolyte content, conduction velocity, and oxidative stress that may reflect the heterogeneous and compartmentalized composition of peripheral nerve.

Animals↗