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Anders A F Sima - One of the best experts on this subject based on the ideXlab platform.
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acetyl l carnitine improves pain Nerve Regeneration and vibratory perception in patients with chronic diabetic neuropathy an analysis of two randomized placebo controlled trials
Diabetes Care, 2005Co-Authors: Anders A F Sima, Menotti Calvani, Munish Mehra, Antonino AmatoAbstract:OBJECTIVE —We evaluated frozen databases from two 52-week randomized placebo-controlled clinical diabetic neuropathy trials testing two doses of acetyl-l-carnitine (ALC): 500 and 1,000 mg/day t.i.d. RESEARCH DESIGN AND METHODS —Intention-to-treat patients amounted to 1,257 or 93% of enrolled patients. Efficacy end points were sural Nerve morphometry, Nerve conduction velocities, vibration perception thresholds, clinical symptom scores, and a visual analogue scale for most bothersome symptom, most notably pain. The two studies were evaluated separately and combined. RESULTS —Data showed significant improvements in sural Nerve Fiber numbers and regenerating Nerve Fiber clusters. Nerve conduction velocities and amplitudes did not improve, whereas vibration perception improved in both studies. Pain as the most bothersome symptom showed significant improvement in one study and in the combined cohort taking 1,000 mg ALC. CONCLUSIONS —These studies demonstrate that ALC treatment is efficacious in alleviating symptoms, particularly pain, and improves Nerve Fiber Regeneration and vibration perception in patients with established diabetic neuropathy.
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proinsulin c peptide replacement in type 1 diabetic bb wor rats prevents deficits in Nerve Fiber Regeneration
Journal of Neuropathology and Experimental Neurology, 2003Co-Authors: Christopher R Pierson, Weixian Zhang, Anders A F SimaAbstract:We recently reported that early gene responses and expression of cytoskeletal proteins are perturbed in regenerating Nerve in type 1 insulinopenic diabetes but not in type 2 hyperinsulinemic diabetes. We hypothesized that these differences were due to impaired insulin action in the former type of diabetes. To test this hypothesis, type 1 diabetic BB/Wor-rats were replaced with proinsulin C-peptide, which enhances insulin signaling without lowering blood glucose. Following sciatic Nerve crush injury, early gene responses such as insulin-like growth factor, c-fos, and Nerve growth factor were examined longitudinally in sciatic Nerve. Neurotrophic factors, their receptors, and β-tubulin and neurofilament expression were examined in dorsal root ganglia. C-peptide replacement significantly normalized early gene responses in injured sciatic Nerve and partially corrected the expression of endogenous neurotrophic factors and their receptors, as well as neuroskeletal protein in dorsal root ganglia. These effects translated into normalization of axonal radial growth and significantly improved axonal elongation of regenerating Fibers in C-peptide-replaced BB/Wor-rats. The findings in C-peptide replaced type 1 diabetic rats were similar to those previously reported in hyperinsulinemic and iso-hyperglycemic type 2 BB/Z-rats. We conclude that impaired insulin action may be more important than hyperglycemia in suppressing Nerve Fiber Regeneration in type 1 diabetic neuropathy.
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effect of hyperglycemia and the aldose reductase inhibitor tolrestat on sural Nerve biochemistry and morphometry in advanced diabetic peripheral polyneuropathy
Journal of Diabetes and Its Complications, 1993Co-Authors: Anders A F Sima, T. C. Hohman, Jay G Graepel, Wieslaw J Bochenek, David Hicks, Douglas A. Greene, Morton B. Brown, Boas GonenAbstract:Abstract 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 dysjunction 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.
Boas Gonen - One of the best experts on this subject based on the ideXlab platform.
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effect of hyperglycemia and the aldose reductase inhibitor tolrestat on sural Nerve biochemistry and morphometry in advanced diabetic peripheral polyneuropathy
Journal of Diabetes and Its Complications, 1993Co-Authors: Anders A F Sima, T. C. Hohman, Jay G Graepel, Wieslaw J Bochenek, David Hicks, Douglas A. Greene, Morton B. Brown, Boas GonenAbstract:Abstract 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 dysjunction 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.
Artur S P Varejao - One of the best experts on this subject based on the ideXlab platform.
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functional and morphological assessment of a standardized crush injury of the rat median Nerve
Journal of Neuroscience Methods, 2009Co-Authors: Giulia Ronchi, Stefania Raimondo, Artur S P Varejao, Maria G Giacobinirobecchi, Pierluigi Tos, S Nicolino, B Battiston, Igor Papalia, Isabelle Perroteau, Stefano GeunaAbstract:The availability of effective experimental models for investigating Nerve Regeneration and designing new strategies for promoting this unique repair process is important. The aim of this study was to standardize a rat median Nerve crush injury model using a non-serrated clamp exerting a compression force of 17.02 MPa for a duration of 30s. Results showed that functional recovery, evaluated by grasping test, was already detectable at day-12 and progressively increased until day-28 after which animal performance plateaued until the end of testing (day-42), reaching a range of 75-80% of pre-operative values. Morphological analysis on the median Nerve segments, distal to the crush lesion, which were withdrawn at the end of the experiment showed that regenerated Nerve Fibers are significantly more numerous and densely packed; they are also smaller and have a thinner myelin sheath compared to controls. Together, these results provide a baseline characterization of the crush median Nerve injury experimental model for its employment in the investigation of Nerve Regeneration research, especially when a reproducible Regeneration process is required, such as for the study of biological mechanisms of peripheral Nerve Fiber Regeneration or development of new therapeutic agents for promoting posttraumatic Nerve repair.
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neural cell transplantation effects on sciatic Nerve Regeneration after a standardized crush injury in the rat
Microsurgery, 2008Co-Authors: Ana Lucia Luis, Maria J Simoes, Sandra Amado, Federica Fregnan, Stefano Geuna, A J A Ferreira, Jorge Rodrigues, Antonio Veloso, Paulo Armadadasilva, Artur S P VarejaoAbstract:The goal of the present study was to assess whether in vitro-differentiated N1E-115 cells supported by a collagen membrane would enhance rat sciatic Nerve Regeneration after a crush injury. To set up an appropriate experimental model for investigating the effects of neural cell transplantation, we have recently described the sequence of functional and morphologic changes occurring after a standardized sciatic Nerve crush injury with a nonserrated clamp. Functional recovery was evaluated using the sciatic functional index, the static sciatic index, the extensor postural thrust, the withdrawal reflex latency, and ankle kinematics. In addition, histomorphometric analysis was carried out on regenerated Nerve Fibers by means of the 2D-disector method. Based on the results of the EPT and of some of the ankle locomotor kinematic parameters analyzed, the hypothesis that N1E-115 cells may enhance Nerve Regeneration is partially supported although histomorphometry disclosed no significant difference in Nerve Fiber Regeneration between the different experimental groups. Therefore, results suggest that enrichment of equine type III collagen membrane with the N1E-115 cellular system in the rat sciatic Nerve crush model may support recovery, at least in terms of motor function. The discrepancy between functional and morphological results also suggests that the combined use of functional and morphological analysis should be recommended for an overall assessment of recovery in Nerve Regeneration studies. © 2008 Wiley-Liss, Inc. Microsurgery, 2008.
T. C. Hohman - One of the best experts on this subject based on the ideXlab platform.
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effect of hyperglycemia and the aldose reductase inhibitor tolrestat on sural Nerve biochemistry and morphometry in advanced diabetic peripheral polyneuropathy
Journal of Diabetes and Its Complications, 1993Co-Authors: Anders A F Sima, T. C. Hohman, Jay G Graepel, Wieslaw J Bochenek, David Hicks, Douglas A. Greene, Morton B. Brown, Boas GonenAbstract:Abstract 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 dysjunction 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.
David Hicks - One of the best experts on this subject based on the ideXlab platform.
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effect of hyperglycemia and the aldose reductase inhibitor tolrestat on sural Nerve biochemistry and morphometry in advanced diabetic peripheral polyneuropathy
Journal of Diabetes and Its Complications, 1993Co-Authors: Anders A F Sima, T. C. Hohman, Jay G Graepel, Wieslaw J Bochenek, David Hicks, Douglas A. Greene, Morton B. Brown, Boas GonenAbstract:Abstract 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 dysjunction 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.