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Mark A. Yorek - One of the best experts on this subject based on the ideXlab platform.

  • Effect of treating streptozotocin-induced diabetic rats with sorbinil, myo-inositol or aminoguanidine on endoneurial blood flow, Motor Nerve Conduction velocity and vascular function of epineurial arterioles of the sciatic Nerve.
    International journal of experimental diabetes research, 2002
    Co-Authors: Lawrence J. Coppey, Joyce A. Dunlap, Jill S. Gellett, Eric P. Davidson, Mark A. Yorek
    Abstract:

    Previously we have demonstrated that diabetes causes impairment in vascular function of epineurial vessels, which precedes the slowing of Motor Nerve Conduction velocity. Treatment of diabetic rats with aldose reductase inhibitors, aminoguanidine or myo-inositol supplementation have been shown to improve Motor Nerve Conduction velocity and/or decreased endoneurial blood flow. However, the effect these treatments have on vascular reactivity of epineurial vessels of the sciatic Nerve is unknown. In these studies we examined the effect of treating streptozotocin-induced rats with sorbinil, aminoguanidine or myo-inositol on Motor Nerve Conduction velocity, endoneurial blood flow and endothelium dependent vascular relaxation of arterioles that provide circulation to the region of the sciatic Nerve. Treating diabetic rats with sorbinil, aminoguanidine or myo-inositol improved the reduction of endoneurial blood flow and Motor Nerve Conduction velocity. However, only sorbinil treatment significantly improved the diabetes-induced impairment of acetylcholinemediated vasodilation of epineurial vessels of the sciatic Nerve. All three treatments were efficacious in preventing the appropriate metabolic derangements associated with either activation of the polyol pathway or increased nonenzymatic glycation. In addition, sorbinil was shown to prevent the diabetes-induced decrease in lens glutathione level. However, other markers of oxidative stress were not vividly improved by these treatments. These studies suggest that sorbinil treatment may be more effective in preventing neural dysfunction in diabetes than either aminoguanidine or myoinositol.

  • changes in endoneurial blood flow Motor Nerve Conduction velocity and vascular relaxation of epineurial arterioles of the sciatic Nerve in zdf obese diabetic rats
    Diabetes-metabolism Research and Reviews, 2002
    Co-Authors: Lawrence J. Coppey, Mark A. Yorek, Joyce A. Dunlap, Jill S. Gellett, Eric P. Davidson
    Abstract:

    Background We have previously reported that in streptozotocin-induced diabetic rats, reduction in endoneurial blood flow (EBF) and impairment of acetylcholine-mediated vascular relaxation of arterioles that provide circulation to the sciatic Nerve precedes slowing of Motor Nerve Conduction velocity (MNCV). However, in animal models of type 2 diabetes it is unknown whether slowing of MNCV is accompanied by vascular dysfunction. Methods Using ZDF-lean and ZDF-obese diabetic rats we examined whether diabetes-induced slowing in MNCV was associated with a reduction in EBF and impaired vascular relaxation in epineurial arterioles of the sciatic Nerve. We measured MNCV in the sciatic Nerve using a non-invasive procedure, and sciatic Nerve nutritive blood flow using microelectrode polarography. In vitro videomicroscopy was employed to quantify arteriolar diameter responses to acetylcholine in arterioles overlying the sciatic Nerve. Results MNCV and EBF in hyperglycemic (4-week duration) ZDF-obese diabetic rats were significantly decreased by 30% and 63%, respectively, compared to age-matched ZDF-lean rats. Acetylcholine elicited a dose-dependent dilation of epineurial vessels from ZDF-lean and ZDF-obese diabetic rats, although acetylcholine-induced dilation was significantly reduced in ZDF-obese diabetic rats. Determination of markers of oxidative stress provided ambiguous results. Superoxide levels were increased in epineurial vessels from ZDF-obese diabetic rats. Lens glutathione levels were decreased and serum thiobarbituric acid reactive substances increased in ZDF-obese diabetic rats but sciatic Nerve conjugated diene and glutathione levels were not significantly different compared to ZDF-lean rats. Conclusions Diabetes causes a reduction in EBF and impairment in vascular relaxation in epineurial vessels in ZDF-obese diabetic rats. This impaired vascular response is associated with neural dysfunction. Copyright © 2002 John Wiley & Sons, Ltd.

  • effect of m40403 treatment of diabetic rats on endoneurial blood flow Motor Nerve Conduction velocity and vascular function of epineurial arterioles of the sciatic Nerve
    British Journal of Pharmacology, 2001
    Co-Authors: Lawrence J. Coppey, Joyce A. Dunlap, Jill S. Gellett, Eric P. Davidson, Donald D Lund, Daniela Salvemini, Mark A. Yorek
    Abstract:

    To further explore the effect of antioxidants in preventing diabetes-induced vascular and neural dysfunction we treated streptozotocin-induced diabetic rats daily with subcutaneous injections of 10 mg kg−1 of M40403 (n=11) and compared the results obtained from 17 control rats and 14 untreated diabetic rats. M40403 is a manganese(II) complex with a bis(cyclo-hexylpyridine)-substituted macrocyclic ligand that was designed to be a selective functional mimetic of superoxide dismutase. Thus, M40403 provides a useful tool to evaluate the roles of superoxide in disease states. Treatment with M40403 significantly improved diabetes-induced decrease in endoneurial blood flow, acetylcholine-mediated vascular relaxation in arterioles that provide circulation to the region of the sciatic Nerve, and Motor Nerve Conduction velocity (P<0.05). M40403 treatment also reduced the appearance of superoxide in the aorta and epineurial vessels and peroxynitrite in epineurial vessels. Treating diabetic rats with M40403 reduced the diabetes-induced increase in thiobarbituric acid reactive substances in serum but did not prevent the decrease in lens glutathione level. Treating diabetic rats with M40403 did not improve sciatic Nerve Na+/K+ ATPase activity or the sorbitol, fructose or myo-inositol content of the sciatic Nerve. These studies provide additional evidence that diabetes-induced oxidative stress and the generation of superoxide and perhaps peroxynitrite may be partially responsible for the development of diabetic vascular and neural complications. British Journal of Pharmacology (2001) 134, 21–29; doi:10.1038/sj.bjp.0704216

  • effect of antioxidant treatment of streptozotocin induced diabetic rats on endoneurial blood flow Motor Nerve Conduction velocity and vascular reactivity of epineurial arterioles of the sciatic Nerve
    Diabetes, 2001
    Co-Authors: Lawrence J. Coppey, Joyce A. Dunlap, Jill S. Gellett, Eric P. Davidson, Donald D Lund, Mark A. Yorek
    Abstract:

    We have shown that diabetes-induced reduction in endoneurial blood flow (EBF) and impaired endothelium-dependent vascular relaxation precede slowing of Motor Nerve Conduction velocity (MNCV) and decreased sciatic Nerve Na + /K + ATPase activity. Furthermore, vascular dysfunction was accompanied by an accumulation of superoxide in arterioles that provide circulation to the sciatic Nerve. In the present study, we examined the effect that treatment of streptozotocin-induced diabetic rats with antioxidants has on vascular and neural function. Diabetic rats were treated with 0.5% α-lipoic acid as a diet supplement or with hydroxyethyl starch deferoxamine (HES-DFO) by weekly intravenous injections at a dose of 75 mg/kg. The treatments significantly improved diabetes-induced decrease in EBF, acetylcholine-mediated vascular relaxation in arterioles that provide circulation to the region of the sciatic Nerve, and MNCV. The treatments also reduced the production of superoxide by the aorta and superoxide and peroxynitrite by arterioles that provide circulation to the region of the sciatic Nerve. Treating diabetic rats with α-lipoic acid prevented the diabetes-induced increase in thiobarbituric acid–reactive substances in serum and significantly improved lens glutathione levels. In contrast, treating diabetic rats with HES-DFO did not prevent diabetes-induced changes of either of these markers of oxidative stress. Diabetes-induced increase in sciatic Nerve conjugated diene levels was not improved by treatment with either α-lipoic acid or HES-DFO. Treating diabetic rats with α-lipoic acid but not HES-DFO partially improved sciatic Nerve Na + /K + ATPase activity and myo -inositol content. The increase in sciatic Nerve sorbitol levels in diabetic rats was unchanged by either treatment. These studies suggest that diabetes-induced oxidative stress and the generation of superoxide may be partially responsible for the development of diabetic vascular and neural complications.

  • effect of antioxidant treatment of streptozotocin induced diabetic rats on endoneurial blood flow Motor Nerve Conduction velocity and vascular reactivity of epineurial arterioles of the sciatic Nerve
    Diabetes, 2001
    Co-Authors: Lawrence J. Coppey, Joyce A. Dunlap, Jill S. Gellett, Eric P. Davidson, Donald D Lund, Mark A. Yorek
    Abstract:

    We have shown that diabetes-induced reduction in endoneurial blood flow (EBF) and impaired endothelium-dependent vascular relaxation precede slowing of Motor Nerve Conduction velocity (MNCV) and decreased sciatic Nerve Na(+)/K(+) ATPase activity. Furthermore, vascular dysfunction was accompanied by an accumulation of superoxide in arterioles that provide circulation to the sciatic Nerve. In the present study, we examined the effect that treatment of streptozotocin-induced diabetic rats with antioxidants has on vascular and neural function. Diabetic rats were treated with 0.5% alpha-lipoic acid as a diet supplement or with hydroxyethyl starch deferoxamine (HES-DFO) by weekly intravenous injections at a dose of 75 mg/kg. The treatments significantly improved diabetes-induced decrease in EBF, acetylcholine-mediated vascular relaxation in arterioles that provide circulation to the region of the sciatic Nerve, and MNCV. The treatments also reduced the production of superoxide by the aorta and superoxide and peroxynitrite by arterioles that provide circulation to the region of the sciatic Nerve. Treating diabetic rats with alpha-lipoic acid prevented the diabetes-induced increase in thiobarbituric acid-reactive substances in serum and significantly improved lens glutathione levels. In contrast, treating diabetic rats with HES-DFO did not prevent diabetes-induced changes of either of these markers of oxidative stress. Diabetes-induced increase in sciatic Nerve conjugated diene levels was not improved by treatment with either alpha-lipoic acid or HES-DFO. Treating diabetic rats with alpha-lipoic acid but not HES-DFO partially improved sciatic Nerve Na(+)/K(+) ATPase activity and myo-inositol content. The increase in sciatic Nerve sorbitol levels in diabetic rats was unchanged by either treatment. These studies suggest that diabetes-induced oxidative stress and the generation of superoxide may be partially responsible for the development of diabetic vascular and neural complications.

Yuzhou Guan - One of the best experts on this subject based on the ideXlab platform.

  • Conduction block and Nerve cross sectional area in multifocal Motor neuropathy
    Frontiers in Neurology, 2019
    Co-Authors: Yi Li, Shuang Wu, Qingyun Ding, Yuzhou Guan
    Abstract:

    Introduction: Motor Nerve Conduction block (CB) is the main electrophysiological feature of multifocal Motor neuropathy (MMN). Increased cross-sectional area (CSA) can be detected by Nerve ultrasound in MMN. In this study, we aim to analyze the correlation between CB and CSA in MMN. Methods: Twelve patients with MMN were recruited. Ultrasonography tests and Motor Nerve Conduction studies were performed on median and ulnar Nerves simultaneously. CSA was measured at 10 consecutive sites on those Nerves， meanwhile Nerves were traced continuously and recorded thoroughly under ultrasound. Results: In Motor Nerve Conduction studies, 12 definite CB and 12 probable CB areas were detected across standard segments of median and ulnar Nerves. With ultrasound studies, increased CSA was detected at 36 sites. There were 9 standard segments with CB and increased CSA, 15 segments with CB but normal CSA, and 27 segments with increased CSA but no CB. Discussion: In MMN, Motor Nerve CB was not always consistent with increased CSA.

  • Conduction block and Nerve cross sectional area in multifocal Motor neuropathy
    Frontiers in Neurology, 2019
    Co-Authors: Jingwen Niu, Yuzhou Guan, Liying Cui, Qingyun Ding, Tanxin Liu, Mingsheng Liu
    Abstract:

    Introduction: Motor Nerve Conduction block (CB) is the main electrophysiological feature of multifocal Motor neuropathy (MMN). Increased cross-sectional area (CSA) can be detected by Nerve ultrasound in MMN. In this study, we aim to analyze the correlation between CB and CSA in MMN. Methods: Twelve patients with MMN were recruited. Ultrasonography tests and Motor Nerve Conduction studies (NCSs) were performed on median and ulnar Nerves simultaneously. CSA was measured at 10 consecutive sites on those Nerves, meanwhile Nerves were traced continuously and recorded thoroughly under ultrasound. Results: In Motor NCSs, 12 definite CB and 12 probable CB areas were detected across standard segments of median and ulnar Nerves. With ultrasound studies, increased CSA was detected at 36 sites. There were 9 standard segments with CB and increased CSA, 15 segments with CB but normal CSA, and 27 segments with increased CSA but no CB. Discussion: In MMN, Motor Nerve CB was not always consistent with increased CSA.

  • Motor Nerve Conduction block predicting outcome of guillain barre syndrome
    Frontiers in Neurology, 2018
    Co-Authors: Yi Li, Shuang Wu, Qingyun Ding, Yuzhou Guan
    Abstract:

    Introduction: Motor Nerve Conduction blocks (CBs) could be detected in both acute inflammatory demyelinating polyradiculoneuropathy (AIDP) and acute Motor axonal neuropathy (AMAN). We aimed to identify the correlation between CBs and functional outcome in the two subtypes of GBS. Methods: Motor Nerve Conduction studies were performed in 17 patients with AIDP and 23 with AMAN. All patients were treated with intravenous immunoglobulin, and their disabilities were evaluated with Hughes functional grading scale before treatment, 1 month and 6 months after onset. Results: AMAN with CBs had higher reduction of Hughes grade (indicating more improved outcomes) at one month (1.71±0.83 vs 1±0.67, p=0.034) than AIDP with CBs. AMAN with CBs had higher reduction of Hughes grade at one month (1.71±0.83 vs 0.56±0.73, p=0.002) than AMAN without CBs. The reduction of Hughes grade at one month showed no significant difference between AIDP with and without CBs. Discussion: Motor Nerve CBs in AMAN indicated better prognosis than in AIDP.

  • Motor Nerve Conduction Block Predicting Outcome of Guillain-Barre Syndrome
    Frontiers Media S.A., 2018
    Co-Authors: Jingwen Niu, Mingsheng Liu, Yuzhou Guan, Qingyun Ding, Qing Sun, Liying Cui
    Abstract:

    Introduction: Motor Nerve Conduction blocks (CBs) could be detected in both acute inflammatory demyelinating polyradiculoneuropathy (AIDP) and acute Motor axonal neuropathy (AMAN). We aimed to identify the correlation between CBs and functional outcome in the two subtypes of GBS.Methods: Motor Nerve Conduction studies were performed in 17 patients with AIDP and 23 with AMAN. All patients were treated with intravenous immunoglobulin, and their disabilities were evaluated with Hughes functional grading scale before treatment, 1 month and 6 months after onset.Results: AMAN with CBs had higher reduction of Hughes grade (indicating more improved outcomes) at 1 month (1.71 ± 0.83 vs. 1 ± 0.67, p = 0.034) than AIDP with CBs. AMAN with CBs had higher reduction of Hughes grade at 1 month (1.71 ± 0.83 vs. 0.56 ± 0.73, p = 0.002) than AMAN without CBs. The reduction of Hughes grade at 1 month showed no significant difference between AIDP with and without CBs.Discussion: Motor Nerve CBs in AMAN indicated better prognosis than in AIDP

  • Motor Nerve Conduction study and muscle strength in newly diagnosed poems syndrome
    Muscle & Nerve, 2015
    Co-Authors: Mingsheng Liu, Zhangyu Zou, Yuzhou Guan, Daobin Zhou, Liying Cui
    Abstract:

    Introduction: Mixed demyelination and axonal loss are electrophysiological features of polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome. It is unclear whether the demyelination and axonal loss occur concurrently. Methods: Electromyography was performed in 37 patients with newly diagnosed POEMS syndrome. Compound muscle action potential (CMAP) amplitude, distal Motor latency, Motor Conduction velocity (MCV), and spontaneous activity were collected. Muscle strength was measured according to the Medical Research Council (MRC) scale. Results: MCV decreased in all Nerves with decreased CMAP amplitude and in 93% of Nerves with normal amplitude. CMAP amplitude decreased in 54% of Nerves with decreased MCV and was normal in all Nerves with normal MCV. MCV deceased in 95% of Nerves with normal MRC. Abnormal spontaneous activity was detected in 32% of upper limb muscles. Conclusions: Demyelination may be the main manifestation in POEMS neuropathy at an early stage, and axonal loss may be secondary to demyelination as the disease progresses. Muscle Nerve 51: 19–23, 2015

Lawrence J. Coppey - One of the best experts on this subject based on the ideXlab platform.

  • Effect of treating streptozotocin-induced diabetic rats with sorbinil, myo-inositol or aminoguanidine on endoneurial blood flow, Motor Nerve Conduction velocity and vascular function of epineurial arterioles of the sciatic Nerve.
    International journal of experimental diabetes research, 2002
    Co-Authors: Lawrence J. Coppey, Joyce A. Dunlap, Jill S. Gellett, Eric P. Davidson, Mark A. Yorek
    Abstract:

    Previously we have demonstrated that diabetes causes impairment in vascular function of epineurial vessels, which precedes the slowing of Motor Nerve Conduction velocity. Treatment of diabetic rats with aldose reductase inhibitors, aminoguanidine or myo-inositol supplementation have been shown to improve Motor Nerve Conduction velocity and/or decreased endoneurial blood flow. However, the effect these treatments have on vascular reactivity of epineurial vessels of the sciatic Nerve is unknown. In these studies we examined the effect of treating streptozotocin-induced rats with sorbinil, aminoguanidine or myo-inositol on Motor Nerve Conduction velocity, endoneurial blood flow and endothelium dependent vascular relaxation of arterioles that provide circulation to the region of the sciatic Nerve. Treating diabetic rats with sorbinil, aminoguanidine or myo-inositol improved the reduction of endoneurial blood flow and Motor Nerve Conduction velocity. However, only sorbinil treatment significantly improved the diabetes-induced impairment of acetylcholinemediated vasodilation of epineurial vessels of the sciatic Nerve. All three treatments were efficacious in preventing the appropriate metabolic derangements associated with either activation of the polyol pathway or increased nonenzymatic glycation. In addition, sorbinil was shown to prevent the diabetes-induced decrease in lens glutathione level. However, other markers of oxidative stress were not vividly improved by these treatments. These studies suggest that sorbinil treatment may be more effective in preventing neural dysfunction in diabetes than either aminoguanidine or myoinositol.

  • changes in endoneurial blood flow Motor Nerve Conduction velocity and vascular relaxation of epineurial arterioles of the sciatic Nerve in zdf obese diabetic rats
    Diabetes-metabolism Research and Reviews, 2002
    Co-Authors: Lawrence J. Coppey, Mark A. Yorek, Joyce A. Dunlap, Jill S. Gellett, Eric P. Davidson
    Abstract:

    Background We have previously reported that in streptozotocin-induced diabetic rats, reduction in endoneurial blood flow (EBF) and impairment of acetylcholine-mediated vascular relaxation of arterioles that provide circulation to the sciatic Nerve precedes slowing of Motor Nerve Conduction velocity (MNCV). However, in animal models of type 2 diabetes it is unknown whether slowing of MNCV is accompanied by vascular dysfunction. Methods Using ZDF-lean and ZDF-obese diabetic rats we examined whether diabetes-induced slowing in MNCV was associated with a reduction in EBF and impaired vascular relaxation in epineurial arterioles of the sciatic Nerve. We measured MNCV in the sciatic Nerve using a non-invasive procedure, and sciatic Nerve nutritive blood flow using microelectrode polarography. In vitro videomicroscopy was employed to quantify arteriolar diameter responses to acetylcholine in arterioles overlying the sciatic Nerve. Results MNCV and EBF in hyperglycemic (4-week duration) ZDF-obese diabetic rats were significantly decreased by 30% and 63%, respectively, compared to age-matched ZDF-lean rats. Acetylcholine elicited a dose-dependent dilation of epineurial vessels from ZDF-lean and ZDF-obese diabetic rats, although acetylcholine-induced dilation was significantly reduced in ZDF-obese diabetic rats. Determination of markers of oxidative stress provided ambiguous results. Superoxide levels were increased in epineurial vessels from ZDF-obese diabetic rats. Lens glutathione levels were decreased and serum thiobarbituric acid reactive substances increased in ZDF-obese diabetic rats but sciatic Nerve conjugated diene and glutathione levels were not significantly different compared to ZDF-lean rats. Conclusions Diabetes causes a reduction in EBF and impairment in vascular relaxation in epineurial vessels in ZDF-obese diabetic rats. This impaired vascular response is associated with neural dysfunction. Copyright © 2002 John Wiley & Sons, Ltd.

  • effect of m40403 treatment of diabetic rats on endoneurial blood flow Motor Nerve Conduction velocity and vascular function of epineurial arterioles of the sciatic Nerve
    British Journal of Pharmacology, 2001
    Co-Authors: Lawrence J. Coppey, Joyce A. Dunlap, Jill S. Gellett, Eric P. Davidson, Donald D Lund, Daniela Salvemini, Mark A. Yorek
    Abstract:

    To further explore the effect of antioxidants in preventing diabetes-induced vascular and neural dysfunction we treated streptozotocin-induced diabetic rats daily with subcutaneous injections of 10 mg kg−1 of M40403 (n=11) and compared the results obtained from 17 control rats and 14 untreated diabetic rats. M40403 is a manganese(II) complex with a bis(cyclo-hexylpyridine)-substituted macrocyclic ligand that was designed to be a selective functional mimetic of superoxide dismutase. Thus, M40403 provides a useful tool to evaluate the roles of superoxide in disease states. Treatment with M40403 significantly improved diabetes-induced decrease in endoneurial blood flow, acetylcholine-mediated vascular relaxation in arterioles that provide circulation to the region of the sciatic Nerve, and Motor Nerve Conduction velocity (P<0.05). M40403 treatment also reduced the appearance of superoxide in the aorta and epineurial vessels and peroxynitrite in epineurial vessels. Treating diabetic rats with M40403 reduced the diabetes-induced increase in thiobarbituric acid reactive substances in serum but did not prevent the decrease in lens glutathione level. Treating diabetic rats with M40403 did not improve sciatic Nerve Na+/K+ ATPase activity or the sorbitol, fructose or myo-inositol content of the sciatic Nerve. These studies provide additional evidence that diabetes-induced oxidative stress and the generation of superoxide and perhaps peroxynitrite may be partially responsible for the development of diabetic vascular and neural complications. British Journal of Pharmacology (2001) 134, 21–29; doi:10.1038/sj.bjp.0704216

  • effect of antioxidant treatment of streptozotocin induced diabetic rats on endoneurial blood flow Motor Nerve Conduction velocity and vascular reactivity of epineurial arterioles of the sciatic Nerve
    Diabetes, 2001
    Co-Authors: Lawrence J. Coppey, Joyce A. Dunlap, Jill S. Gellett, Eric P. Davidson, Donald D Lund, Mark A. Yorek
    Abstract:

    We have shown that diabetes-induced reduction in endoneurial blood flow (EBF) and impaired endothelium-dependent vascular relaxation precede slowing of Motor Nerve Conduction velocity (MNCV) and decreased sciatic Nerve Na + /K + ATPase activity. Furthermore, vascular dysfunction was accompanied by an accumulation of superoxide in arterioles that provide circulation to the sciatic Nerve. In the present study, we examined the effect that treatment of streptozotocin-induced diabetic rats with antioxidants has on vascular and neural function. Diabetic rats were treated with 0.5% α-lipoic acid as a diet supplement or with hydroxyethyl starch deferoxamine (HES-DFO) by weekly intravenous injections at a dose of 75 mg/kg. The treatments significantly improved diabetes-induced decrease in EBF, acetylcholine-mediated vascular relaxation in arterioles that provide circulation to the region of the sciatic Nerve, and MNCV. The treatments also reduced the production of superoxide by the aorta and superoxide and peroxynitrite by arterioles that provide circulation to the region of the sciatic Nerve. Treating diabetic rats with α-lipoic acid prevented the diabetes-induced increase in thiobarbituric acid–reactive substances in serum and significantly improved lens glutathione levels. In contrast, treating diabetic rats with HES-DFO did not prevent diabetes-induced changes of either of these markers of oxidative stress. Diabetes-induced increase in sciatic Nerve conjugated diene levels was not improved by treatment with either α-lipoic acid or HES-DFO. Treating diabetic rats with α-lipoic acid but not HES-DFO partially improved sciatic Nerve Na + /K + ATPase activity and myo -inositol content. The increase in sciatic Nerve sorbitol levels in diabetic rats was unchanged by either treatment. These studies suggest that diabetes-induced oxidative stress and the generation of superoxide may be partially responsible for the development of diabetic vascular and neural complications.

  • effect of antioxidant treatment of streptozotocin induced diabetic rats on endoneurial blood flow Motor Nerve Conduction velocity and vascular reactivity of epineurial arterioles of the sciatic Nerve
    Diabetes, 2001
    Co-Authors: Lawrence J. Coppey, Joyce A. Dunlap, Jill S. Gellett, Eric P. Davidson, Donald D Lund, Mark A. Yorek
    Abstract:

    We have shown that diabetes-induced reduction in endoneurial blood flow (EBF) and impaired endothelium-dependent vascular relaxation precede slowing of Motor Nerve Conduction velocity (MNCV) and decreased sciatic Nerve Na(+)/K(+) ATPase activity. Furthermore, vascular dysfunction was accompanied by an accumulation of superoxide in arterioles that provide circulation to the sciatic Nerve. In the present study, we examined the effect that treatment of streptozotocin-induced diabetic rats with antioxidants has on vascular and neural function. Diabetic rats were treated with 0.5% alpha-lipoic acid as a diet supplement or with hydroxyethyl starch deferoxamine (HES-DFO) by weekly intravenous injections at a dose of 75 mg/kg. The treatments significantly improved diabetes-induced decrease in EBF, acetylcholine-mediated vascular relaxation in arterioles that provide circulation to the region of the sciatic Nerve, and MNCV. The treatments also reduced the production of superoxide by the aorta and superoxide and peroxynitrite by arterioles that provide circulation to the region of the sciatic Nerve. Treating diabetic rats with alpha-lipoic acid prevented the diabetes-induced increase in thiobarbituric acid-reactive substances in serum and significantly improved lens glutathione levels. In contrast, treating diabetic rats with HES-DFO did not prevent diabetes-induced changes of either of these markers of oxidative stress. Diabetes-induced increase in sciatic Nerve conjugated diene levels was not improved by treatment with either alpha-lipoic acid or HES-DFO. Treating diabetic rats with alpha-lipoic acid but not HES-DFO partially improved sciatic Nerve Na(+)/K(+) ATPase activity and myo-inositol content. The increase in sciatic Nerve sorbitol levels in diabetic rats was unchanged by either treatment. These studies suggest that diabetes-induced oxidative stress and the generation of superoxide may be partially responsible for the development of diabetic vascular and neural complications.

Joyce A. Dunlap - One of the best experts on this subject based on the ideXlab platform.

  • Effect of treating streptozotocin-induced diabetic rats with sorbinil, myo-inositol or aminoguanidine on endoneurial blood flow, Motor Nerve Conduction velocity and vascular function of epineurial arterioles of the sciatic Nerve.
    International journal of experimental diabetes research, 2002
    Co-Authors: Lawrence J. Coppey, Joyce A. Dunlap, Jill S. Gellett, Eric P. Davidson, Mark A. Yorek
    Abstract:

    Previously we have demonstrated that diabetes causes impairment in vascular function of epineurial vessels, which precedes the slowing of Motor Nerve Conduction velocity. Treatment of diabetic rats with aldose reductase inhibitors, aminoguanidine or myo-inositol supplementation have been shown to improve Motor Nerve Conduction velocity and/or decreased endoneurial blood flow. However, the effect these treatments have on vascular reactivity of epineurial vessels of the sciatic Nerve is unknown. In these studies we examined the effect of treating streptozotocin-induced rats with sorbinil, aminoguanidine or myo-inositol on Motor Nerve Conduction velocity, endoneurial blood flow and endothelium dependent vascular relaxation of arterioles that provide circulation to the region of the sciatic Nerve. Treating diabetic rats with sorbinil, aminoguanidine or myo-inositol improved the reduction of endoneurial blood flow and Motor Nerve Conduction velocity. However, only sorbinil treatment significantly improved the diabetes-induced impairment of acetylcholinemediated vasodilation of epineurial vessels of the sciatic Nerve. All three treatments were efficacious in preventing the appropriate metabolic derangements associated with either activation of the polyol pathway or increased nonenzymatic glycation. In addition, sorbinil was shown to prevent the diabetes-induced decrease in lens glutathione level. However, other markers of oxidative stress were not vividly improved by these treatments. These studies suggest that sorbinil treatment may be more effective in preventing neural dysfunction in diabetes than either aminoguanidine or myoinositol.

  • changes in endoneurial blood flow Motor Nerve Conduction velocity and vascular relaxation of epineurial arterioles of the sciatic Nerve in zdf obese diabetic rats
    Diabetes-metabolism Research and Reviews, 2002
    Co-Authors: Lawrence J. Coppey, Mark A. Yorek, Joyce A. Dunlap, Jill S. Gellett, Eric P. Davidson
    Abstract:

    Background We have previously reported that in streptozotocin-induced diabetic rats, reduction in endoneurial blood flow (EBF) and impairment of acetylcholine-mediated vascular relaxation of arterioles that provide circulation to the sciatic Nerve precedes slowing of Motor Nerve Conduction velocity (MNCV). However, in animal models of type 2 diabetes it is unknown whether slowing of MNCV is accompanied by vascular dysfunction. Methods Using ZDF-lean and ZDF-obese diabetic rats we examined whether diabetes-induced slowing in MNCV was associated with a reduction in EBF and impaired vascular relaxation in epineurial arterioles of the sciatic Nerve. We measured MNCV in the sciatic Nerve using a non-invasive procedure, and sciatic Nerve nutritive blood flow using microelectrode polarography. In vitro videomicroscopy was employed to quantify arteriolar diameter responses to acetylcholine in arterioles overlying the sciatic Nerve. Results MNCV and EBF in hyperglycemic (4-week duration) ZDF-obese diabetic rats were significantly decreased by 30% and 63%, respectively, compared to age-matched ZDF-lean rats. Acetylcholine elicited a dose-dependent dilation of epineurial vessels from ZDF-lean and ZDF-obese diabetic rats, although acetylcholine-induced dilation was significantly reduced in ZDF-obese diabetic rats. Determination of markers of oxidative stress provided ambiguous results. Superoxide levels were increased in epineurial vessels from ZDF-obese diabetic rats. Lens glutathione levels were decreased and serum thiobarbituric acid reactive substances increased in ZDF-obese diabetic rats but sciatic Nerve conjugated diene and glutathione levels were not significantly different compared to ZDF-lean rats. Conclusions Diabetes causes a reduction in EBF and impairment in vascular relaxation in epineurial vessels in ZDF-obese diabetic rats. This impaired vascular response is associated with neural dysfunction. Copyright © 2002 John Wiley & Sons, Ltd.

  • effect of m40403 treatment of diabetic rats on endoneurial blood flow Motor Nerve Conduction velocity and vascular function of epineurial arterioles of the sciatic Nerve
    British Journal of Pharmacology, 2001
    Co-Authors: Lawrence J. Coppey, Joyce A. Dunlap, Jill S. Gellett, Eric P. Davidson, Donald D Lund, Daniela Salvemini, Mark A. Yorek
    Abstract:

    To further explore the effect of antioxidants in preventing diabetes-induced vascular and neural dysfunction we treated streptozotocin-induced diabetic rats daily with subcutaneous injections of 10 mg kg−1 of M40403 (n=11) and compared the results obtained from 17 control rats and 14 untreated diabetic rats. M40403 is a manganese(II) complex with a bis(cyclo-hexylpyridine)-substituted macrocyclic ligand that was designed to be a selective functional mimetic of superoxide dismutase. Thus, M40403 provides a useful tool to evaluate the roles of superoxide in disease states. Treatment with M40403 significantly improved diabetes-induced decrease in endoneurial blood flow, acetylcholine-mediated vascular relaxation in arterioles that provide circulation to the region of the sciatic Nerve, and Motor Nerve Conduction velocity (P<0.05). M40403 treatment also reduced the appearance of superoxide in the aorta and epineurial vessels and peroxynitrite in epineurial vessels. Treating diabetic rats with M40403 reduced the diabetes-induced increase in thiobarbituric acid reactive substances in serum but did not prevent the decrease in lens glutathione level. Treating diabetic rats with M40403 did not improve sciatic Nerve Na+/K+ ATPase activity or the sorbitol, fructose or myo-inositol content of the sciatic Nerve. These studies provide additional evidence that diabetes-induced oxidative stress and the generation of superoxide and perhaps peroxynitrite may be partially responsible for the development of diabetic vascular and neural complications. British Journal of Pharmacology (2001) 134, 21–29; doi:10.1038/sj.bjp.0704216

  • effect of antioxidant treatment of streptozotocin induced diabetic rats on endoneurial blood flow Motor Nerve Conduction velocity and vascular reactivity of epineurial arterioles of the sciatic Nerve
    Diabetes, 2001
    Co-Authors: Lawrence J. Coppey, Joyce A. Dunlap, Jill S. Gellett, Eric P. Davidson, Donald D Lund, Mark A. Yorek
    Abstract:

    We have shown that diabetes-induced reduction in endoneurial blood flow (EBF) and impaired endothelium-dependent vascular relaxation precede slowing of Motor Nerve Conduction velocity (MNCV) and decreased sciatic Nerve Na + /K + ATPase activity. Furthermore, vascular dysfunction was accompanied by an accumulation of superoxide in arterioles that provide circulation to the sciatic Nerve. In the present study, we examined the effect that treatment of streptozotocin-induced diabetic rats with antioxidants has on vascular and neural function. Diabetic rats were treated with 0.5% α-lipoic acid as a diet supplement or with hydroxyethyl starch deferoxamine (HES-DFO) by weekly intravenous injections at a dose of 75 mg/kg. The treatments significantly improved diabetes-induced decrease in EBF, acetylcholine-mediated vascular relaxation in arterioles that provide circulation to the region of the sciatic Nerve, and MNCV. The treatments also reduced the production of superoxide by the aorta and superoxide and peroxynitrite by arterioles that provide circulation to the region of the sciatic Nerve. Treating diabetic rats with α-lipoic acid prevented the diabetes-induced increase in thiobarbituric acid–reactive substances in serum and significantly improved lens glutathione levels. In contrast, treating diabetic rats with HES-DFO did not prevent diabetes-induced changes of either of these markers of oxidative stress. Diabetes-induced increase in sciatic Nerve conjugated diene levels was not improved by treatment with either α-lipoic acid or HES-DFO. Treating diabetic rats with α-lipoic acid but not HES-DFO partially improved sciatic Nerve Na + /K + ATPase activity and myo -inositol content. The increase in sciatic Nerve sorbitol levels in diabetic rats was unchanged by either treatment. These studies suggest that diabetes-induced oxidative stress and the generation of superoxide may be partially responsible for the development of diabetic vascular and neural complications.

  • effect of antioxidant treatment of streptozotocin induced diabetic rats on endoneurial blood flow Motor Nerve Conduction velocity and vascular reactivity of epineurial arterioles of the sciatic Nerve
    Diabetes, 2001
    Co-Authors: Lawrence J. Coppey, Joyce A. Dunlap, Jill S. Gellett, Eric P. Davidson, Donald D Lund, Mark A. Yorek
    Abstract:

    We have shown that diabetes-induced reduction in endoneurial blood flow (EBF) and impaired endothelium-dependent vascular relaxation precede slowing of Motor Nerve Conduction velocity (MNCV) and decreased sciatic Nerve Na(+)/K(+) ATPase activity. Furthermore, vascular dysfunction was accompanied by an accumulation of superoxide in arterioles that provide circulation to the sciatic Nerve. In the present study, we examined the effect that treatment of streptozotocin-induced diabetic rats with antioxidants has on vascular and neural function. Diabetic rats were treated with 0.5% alpha-lipoic acid as a diet supplement or with hydroxyethyl starch deferoxamine (HES-DFO) by weekly intravenous injections at a dose of 75 mg/kg. The treatments significantly improved diabetes-induced decrease in EBF, acetylcholine-mediated vascular relaxation in arterioles that provide circulation to the region of the sciatic Nerve, and MNCV. The treatments also reduced the production of superoxide by the aorta and superoxide and peroxynitrite by arterioles that provide circulation to the region of the sciatic Nerve. Treating diabetic rats with alpha-lipoic acid prevented the diabetes-induced increase in thiobarbituric acid-reactive substances in serum and significantly improved lens glutathione levels. In contrast, treating diabetic rats with HES-DFO did not prevent diabetes-induced changes of either of these markers of oxidative stress. Diabetes-induced increase in sciatic Nerve conjugated diene levels was not improved by treatment with either alpha-lipoic acid or HES-DFO. Treating diabetic rats with alpha-lipoic acid but not HES-DFO partially improved sciatic Nerve Na(+)/K(+) ATPase activity and myo-inositol content. The increase in sciatic Nerve sorbitol levels in diabetic rats was unchanged by either treatment. These studies suggest that diabetes-induced oxidative stress and the generation of superoxide may be partially responsible for the development of diabetic vascular and neural complications.

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  • Effect of treating streptozotocin-induced diabetic rats with sorbinil, myo-inositol or aminoguanidine on endoneurial blood flow, Motor Nerve Conduction velocity and vascular function of epineurial arterioles of the sciatic Nerve.
    International journal of experimental diabetes research, 2002
    Co-Authors: Lawrence J. Coppey, Joyce A. Dunlap, Jill S. Gellett, Eric P. Davidson, Mark A. Yorek
    Abstract:

    Previously we have demonstrated that diabetes causes impairment in vascular function of epineurial vessels, which precedes the slowing of Motor Nerve Conduction velocity. Treatment of diabetic rats with aldose reductase inhibitors, aminoguanidine or myo-inositol supplementation have been shown to improve Motor Nerve Conduction velocity and/or decreased endoneurial blood flow. However, the effect these treatments have on vascular reactivity of epineurial vessels of the sciatic Nerve is unknown. In these studies we examined the effect of treating streptozotocin-induced rats with sorbinil, aminoguanidine or myo-inositol on Motor Nerve Conduction velocity, endoneurial blood flow and endothelium dependent vascular relaxation of arterioles that provide circulation to the region of the sciatic Nerve. Treating diabetic rats with sorbinil, aminoguanidine or myo-inositol improved the reduction of endoneurial blood flow and Motor Nerve Conduction velocity. However, only sorbinil treatment significantly improved the diabetes-induced impairment of acetylcholinemediated vasodilation of epineurial vessels of the sciatic Nerve. All three treatments were efficacious in preventing the appropriate metabolic derangements associated with either activation of the polyol pathway or increased nonenzymatic glycation. In addition, sorbinil was shown to prevent the diabetes-induced decrease in lens glutathione level. However, other markers of oxidative stress were not vividly improved by these treatments. These studies suggest that sorbinil treatment may be more effective in preventing neural dysfunction in diabetes than either aminoguanidine or myoinositol.

  • changes in endoneurial blood flow Motor Nerve Conduction velocity and vascular relaxation of epineurial arterioles of the sciatic Nerve in zdf obese diabetic rats
    Diabetes-metabolism Research and Reviews, 2002
    Co-Authors: Lawrence J. Coppey, Mark A. Yorek, Joyce A. Dunlap, Jill S. Gellett, Eric P. Davidson
    Abstract:

    Background We have previously reported that in streptozotocin-induced diabetic rats, reduction in endoneurial blood flow (EBF) and impairment of acetylcholine-mediated vascular relaxation of arterioles that provide circulation to the sciatic Nerve precedes slowing of Motor Nerve Conduction velocity (MNCV). However, in animal models of type 2 diabetes it is unknown whether slowing of MNCV is accompanied by vascular dysfunction. Methods Using ZDF-lean and ZDF-obese diabetic rats we examined whether diabetes-induced slowing in MNCV was associated with a reduction in EBF and impaired vascular relaxation in epineurial arterioles of the sciatic Nerve. We measured MNCV in the sciatic Nerve using a non-invasive procedure, and sciatic Nerve nutritive blood flow using microelectrode polarography. In vitro videomicroscopy was employed to quantify arteriolar diameter responses to acetylcholine in arterioles overlying the sciatic Nerve. Results MNCV and EBF in hyperglycemic (4-week duration) ZDF-obese diabetic rats were significantly decreased by 30% and 63%, respectively, compared to age-matched ZDF-lean rats. Acetylcholine elicited a dose-dependent dilation of epineurial vessels from ZDF-lean and ZDF-obese diabetic rats, although acetylcholine-induced dilation was significantly reduced in ZDF-obese diabetic rats. Determination of markers of oxidative stress provided ambiguous results. Superoxide levels were increased in epineurial vessels from ZDF-obese diabetic rats. Lens glutathione levels were decreased and serum thiobarbituric acid reactive substances increased in ZDF-obese diabetic rats but sciatic Nerve conjugated diene and glutathione levels were not significantly different compared to ZDF-lean rats. Conclusions Diabetes causes a reduction in EBF and impairment in vascular relaxation in epineurial vessels in ZDF-obese diabetic rats. This impaired vascular response is associated with neural dysfunction. Copyright © 2002 John Wiley & Sons, Ltd.

  • effect of m40403 treatment of diabetic rats on endoneurial blood flow Motor Nerve Conduction velocity and vascular function of epineurial arterioles of the sciatic Nerve
    British Journal of Pharmacology, 2001
    Co-Authors: Lawrence J. Coppey, Joyce A. Dunlap, Jill S. Gellett, Eric P. Davidson, Donald D Lund, Daniela Salvemini, Mark A. Yorek
    Abstract:

    To further explore the effect of antioxidants in preventing diabetes-induced vascular and neural dysfunction we treated streptozotocin-induced diabetic rats daily with subcutaneous injections of 10 mg kg−1 of M40403 (n=11) and compared the results obtained from 17 control rats and 14 untreated diabetic rats. M40403 is a manganese(II) complex with a bis(cyclo-hexylpyridine)-substituted macrocyclic ligand that was designed to be a selective functional mimetic of superoxide dismutase. Thus, M40403 provides a useful tool to evaluate the roles of superoxide in disease states. Treatment with M40403 significantly improved diabetes-induced decrease in endoneurial blood flow, acetylcholine-mediated vascular relaxation in arterioles that provide circulation to the region of the sciatic Nerve, and Motor Nerve Conduction velocity (P<0.05). M40403 treatment also reduced the appearance of superoxide in the aorta and epineurial vessels and peroxynitrite in epineurial vessels. Treating diabetic rats with M40403 reduced the diabetes-induced increase in thiobarbituric acid reactive substances in serum but did not prevent the decrease in lens glutathione level. Treating diabetic rats with M40403 did not improve sciatic Nerve Na+/K+ ATPase activity or the sorbitol, fructose or myo-inositol content of the sciatic Nerve. These studies provide additional evidence that diabetes-induced oxidative stress and the generation of superoxide and perhaps peroxynitrite may be partially responsible for the development of diabetic vascular and neural complications. British Journal of Pharmacology (2001) 134, 21–29; doi:10.1038/sj.bjp.0704216

  • effect of antioxidant treatment of streptozotocin induced diabetic rats on endoneurial blood flow Motor Nerve Conduction velocity and vascular reactivity of epineurial arterioles of the sciatic Nerve
    Diabetes, 2001
    Co-Authors: Lawrence J. Coppey, Joyce A. Dunlap, Jill S. Gellett, Eric P. Davidson, Donald D Lund, Mark A. Yorek
    Abstract:

    We have shown that diabetes-induced reduction in endoneurial blood flow (EBF) and impaired endothelium-dependent vascular relaxation precede slowing of Motor Nerve Conduction velocity (MNCV) and decreased sciatic Nerve Na + /K + ATPase activity. Furthermore, vascular dysfunction was accompanied by an accumulation of superoxide in arterioles that provide circulation to the sciatic Nerve. In the present study, we examined the effect that treatment of streptozotocin-induced diabetic rats with antioxidants has on vascular and neural function. Diabetic rats were treated with 0.5% α-lipoic acid as a diet supplement or with hydroxyethyl starch deferoxamine (HES-DFO) by weekly intravenous injections at a dose of 75 mg/kg. The treatments significantly improved diabetes-induced decrease in EBF, acetylcholine-mediated vascular relaxation in arterioles that provide circulation to the region of the sciatic Nerve, and MNCV. The treatments also reduced the production of superoxide by the aorta and superoxide and peroxynitrite by arterioles that provide circulation to the region of the sciatic Nerve. Treating diabetic rats with α-lipoic acid prevented the diabetes-induced increase in thiobarbituric acid–reactive substances in serum and significantly improved lens glutathione levels. In contrast, treating diabetic rats with HES-DFO did not prevent diabetes-induced changes of either of these markers of oxidative stress. Diabetes-induced increase in sciatic Nerve conjugated diene levels was not improved by treatment with either α-lipoic acid or HES-DFO. Treating diabetic rats with α-lipoic acid but not HES-DFO partially improved sciatic Nerve Na + /K + ATPase activity and myo -inositol content. The increase in sciatic Nerve sorbitol levels in diabetic rats was unchanged by either treatment. These studies suggest that diabetes-induced oxidative stress and the generation of superoxide may be partially responsible for the development of diabetic vascular and neural complications.

  • effect of antioxidant treatment of streptozotocin induced diabetic rats on endoneurial blood flow Motor Nerve Conduction velocity and vascular reactivity of epineurial arterioles of the sciatic Nerve
    Diabetes, 2001
    Co-Authors: Lawrence J. Coppey, Joyce A. Dunlap, Jill S. Gellett, Eric P. Davidson, Donald D Lund, Mark A. Yorek
    Abstract:

    We have shown that diabetes-induced reduction in endoneurial blood flow (EBF) and impaired endothelium-dependent vascular relaxation precede slowing of Motor Nerve Conduction velocity (MNCV) and decreased sciatic Nerve Na(+)/K(+) ATPase activity. Furthermore, vascular dysfunction was accompanied by an accumulation of superoxide in arterioles that provide circulation to the sciatic Nerve. In the present study, we examined the effect that treatment of streptozotocin-induced diabetic rats with antioxidants has on vascular and neural function. Diabetic rats were treated with 0.5% alpha-lipoic acid as a diet supplement or with hydroxyethyl starch deferoxamine (HES-DFO) by weekly intravenous injections at a dose of 75 mg/kg. The treatments significantly improved diabetes-induced decrease in EBF, acetylcholine-mediated vascular relaxation in arterioles that provide circulation to the region of the sciatic Nerve, and MNCV. The treatments also reduced the production of superoxide by the aorta and superoxide and peroxynitrite by arterioles that provide circulation to the region of the sciatic Nerve. Treating diabetic rats with alpha-lipoic acid prevented the diabetes-induced increase in thiobarbituric acid-reactive substances in serum and significantly improved lens glutathione levels. In contrast, treating diabetic rats with HES-DFO did not prevent diabetes-induced changes of either of these markers of oxidative stress. Diabetes-induced increase in sciatic Nerve conjugated diene levels was not improved by treatment with either alpha-lipoic acid or HES-DFO. Treating diabetic rats with alpha-lipoic acid but not HES-DFO partially improved sciatic Nerve Na(+)/K(+) ATPase activity and myo-inositol content. The increase in sciatic Nerve sorbitol levels in diabetic rats was unchanged by either treatment. These studies suggest that diabetes-induced oxidative stress and the generation of superoxide may be partially responsible for the development of diabetic vascular and neural complications.