The Experts below are selected from a list of 207 Experts worldwide ranked by ideXlab platform
Brian L. Davis - One of the best experts on this subject based on the ideXlab platform.
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Simultaneous shear and pressure sensor array for assessing pressure and shear at foot/ground interface
Journal of Biomechanics, 2006Co-Authors: Jeffrey R. Mackey, Brian L. DavisAbstract:Foot ulceration is a Diabetic Complication estimated to result in over $1 billion worth of medical expenses per year in the United States alone. This multifaceted problem involves the response of plantar soft tissue to both external forces applied to the epidermis and internal changes such as vascular supply and neuropathy. Increasing evidence indicates that a combination of elevated external forces (pressure and shear) and altered tissue properties is key to the etiology of foot ulcers. The overall goal of this research is to develop a platform-type hardware system that will allow a clinician to measure three-dimensional stress tensors (i.e. pressure and shear patterns) on the plantar surface and identify areas of concern. Experimental results have demonstrated that an optical approach can provide clear indication of both shear and pressure from 50 to 400 kPa with a frequency response of 100 Hz, a stress measurement accuracy of 100 Pa and a spatial resolution of 8.0 mm. Initial evaluation of the system shows strong correlation between (i) applied shear and normal stress loads and (ii) the optical phase retardance computed for each stress axis of the polymer-based stress-sensing elements. These special sensing elements are designed to minimize the need for repeated calibration procedures-an issue that has plagued other attempts to develop multisensor shear and pressure systems. © 2005 Elsevier Ltd. All rights reserved.
Eva L Feldman - One of the best experts on this subject based on the ideXlab platform.
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Diabetic neuropathy: cellular mechanisms as therapeutic targets
Nature Reviews Neurology, 2011Co-Authors: Andrea M Vincent, Brian C. Callaghan, Andrea L. Smith, Eva L FeldmanAbstract:Neuropathy is the most common Complication of diabetes and considerably reduces patient quality of life, yet no disease-modifying therapies are currently available and symptomatic treatments generally provide only partial relief. Vincent and colleagues provide an update on the cellular mechanisms that lead to Diabetic neuropathy, which involves a complex interplay between oxidative and inflammatory pathways in neurons, Schwann cells and the microvascular endothelium. The authors highlight potential new therapeutic targets and discuss drug candidates that are in development for this debilitating Diabetic Complication. In patients with diabetes, nerve injury is a common Complication that leads to chronic pain, numbness and substantial loss of quality of life. Good glycemic control can decrease the incidence of Diabetic neuropathy, but more than half of all patients with diabetes still develop this Complication. There is no approved treatment to prevent or halt Diabetic neuropathy, and only symptomatic pain therapies, with variable efficacy, are available. New insights into the mechanisms leading to the development of Diabetic neuropathy continue to point to systemic and cellular imbalances in metabolites of glucose and lipids. In the PNS, sensory neurons, Schwann cells and the microvascular endothelium are vulnerable to oxidative and inflammatory stress in the presence of these altered metabolic substrates. This Review discusses the emerging cellular mechanisms that are activated in the Diabetic milieu of hyperglycemia, dyslipidemia and impaired insulin signaling. We highlight the pathways to cellular injury, thereby identifying promising therapeutic targets, including mitochondrial function and inflammation. Multiple metabolic imbalances underlie the development of Diabetic neuropathy Hyperglycemia, dyslipidemia and cardiovascular dysfunction are each independent risk factors for neuropathy Targeting risk factors as well as cellular oxidative stress and inflammation will be important in future treatment approaches Injury to neurons, Schwann cells and microvascular endothelial cells in the Diabetic milieu contributes to the pathogenesis of neuropathy
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receptor for advanced glycation end products activation injures primary sensory neurons via oxidative stress
Endocrinology, 2007Co-Authors: Andrea M Vincent, Lorena Perrone, Kelli A Sullivan, Carey Backus, Ann Marie Sastry, Christian M Lastoskie, Eva L FeldmanAbstract:The receptor for advanced glycation end products (RAGE) may promote Diabetic vascular and renal disease through the activation of intracellular signaling pathways that promote oxidative stress. Oxidative stress is a mediator of hyperglycemia-induced cell injury and a unifying theme for all mechanisms of Diabetic Complications, but there are few studies on the expression and potential contribution of RAGE in Diabetic neuropathy. The current study demonstrates that dorsal root ganglia neurons express functional RAGE and respond to the RAGE ligand S100 with similar downstream signaling, oxidative stress, and cellular injury as other Diabetic Complication-prone tissues. RAGE-induced phosphatidylinositol-3 kinase activity is associated with formation of reactive oxygen species, caspase-3 activation, and nuclear DNA degradation. These events are prevented by treatment with the antioxidant α-lipoic acid. Our data indicate that therapies aimed at decreasing RAGE ligands, blocking RAGE signaling, or preventing oxi...
Jeffrey R. Mackey - One of the best experts on this subject based on the ideXlab platform.
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Simultaneous shear and pressure sensor array for assessing pressure and shear at foot/ground interface
Journal of Biomechanics, 2006Co-Authors: Jeffrey R. Mackey, Brian L. DavisAbstract:Foot ulceration is a Diabetic Complication estimated to result in over $1 billion worth of medical expenses per year in the United States alone. This multifaceted problem involves the response of plantar soft tissue to both external forces applied to the epidermis and internal changes such as vascular supply and neuropathy. Increasing evidence indicates that a combination of elevated external forces (pressure and shear) and altered tissue properties is key to the etiology of foot ulcers. The overall goal of this research is to develop a platform-type hardware system that will allow a clinician to measure three-dimensional stress tensors (i.e. pressure and shear patterns) on the plantar surface and identify areas of concern. Experimental results have demonstrated that an optical approach can provide clear indication of both shear and pressure from 50 to 400 kPa with a frequency response of 100 Hz, a stress measurement accuracy of 100 Pa and a spatial resolution of 8.0 mm. Initial evaluation of the system shows strong correlation between (i) applied shear and normal stress loads and (ii) the optical phase retardance computed for each stress axis of the polymer-based stress-sensing elements. These special sensing elements are designed to minimize the need for repeated calibration procedures-an issue that has plagued other attempts to develop multisensor shear and pressure systems. © 2005 Elsevier Ltd. All rights reserved.
Andrea M Vincent - One of the best experts on this subject based on the ideXlab platform.
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Diabetic neuropathy: cellular mechanisms as therapeutic targets
Nature Reviews Neurology, 2011Co-Authors: Andrea M Vincent, Brian C. Callaghan, Andrea L. Smith, Eva L FeldmanAbstract:Neuropathy is the most common Complication of diabetes and considerably reduces patient quality of life, yet no disease-modifying therapies are currently available and symptomatic treatments generally provide only partial relief. Vincent and colleagues provide an update on the cellular mechanisms that lead to Diabetic neuropathy, which involves a complex interplay between oxidative and inflammatory pathways in neurons, Schwann cells and the microvascular endothelium. The authors highlight potential new therapeutic targets and discuss drug candidates that are in development for this debilitating Diabetic Complication. In patients with diabetes, nerve injury is a common Complication that leads to chronic pain, numbness and substantial loss of quality of life. Good glycemic control can decrease the incidence of Diabetic neuropathy, but more than half of all patients with diabetes still develop this Complication. There is no approved treatment to prevent or halt Diabetic neuropathy, and only symptomatic pain therapies, with variable efficacy, are available. New insights into the mechanisms leading to the development of Diabetic neuropathy continue to point to systemic and cellular imbalances in metabolites of glucose and lipids. In the PNS, sensory neurons, Schwann cells and the microvascular endothelium are vulnerable to oxidative and inflammatory stress in the presence of these altered metabolic substrates. This Review discusses the emerging cellular mechanisms that are activated in the Diabetic milieu of hyperglycemia, dyslipidemia and impaired insulin signaling. We highlight the pathways to cellular injury, thereby identifying promising therapeutic targets, including mitochondrial function and inflammation. Multiple metabolic imbalances underlie the development of Diabetic neuropathy Hyperglycemia, dyslipidemia and cardiovascular dysfunction are each independent risk factors for neuropathy Targeting risk factors as well as cellular oxidative stress and inflammation will be important in future treatment approaches Injury to neurons, Schwann cells and microvascular endothelial cells in the Diabetic milieu contributes to the pathogenesis of neuropathy
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receptor for advanced glycation end products activation injures primary sensory neurons via oxidative stress
Endocrinology, 2007Co-Authors: Andrea M Vincent, Lorena Perrone, Kelli A Sullivan, Carey Backus, Ann Marie Sastry, Christian M Lastoskie, Eva L FeldmanAbstract:The receptor for advanced glycation end products (RAGE) may promote Diabetic vascular and renal disease through the activation of intracellular signaling pathways that promote oxidative stress. Oxidative stress is a mediator of hyperglycemia-induced cell injury and a unifying theme for all mechanisms of Diabetic Complications, but there are few studies on the expression and potential contribution of RAGE in Diabetic neuropathy. The current study demonstrates that dorsal root ganglia neurons express functional RAGE and respond to the RAGE ligand S100 with similar downstream signaling, oxidative stress, and cellular injury as other Diabetic Complication-prone tissues. RAGE-induced phosphatidylinositol-3 kinase activity is associated with formation of reactive oxygen species, caspase-3 activation, and nuclear DNA degradation. These events are prevented by treatment with the antioxidant α-lipoic acid. Our data indicate that therapies aimed at decreasing RAGE ligands, blocking RAGE signaling, or preventing oxi...
Philip S Tsao - One of the best experts on this subject based on the ideXlab platform.
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plasma concentrations of asymmetric dimethylarginine are increased in patients with type 2 diabetes mellitus
American Journal of Cardiology, 2001Co-Authors: Fahim Abbasi, Tomoko Asagmi, John P Cooke, Cindy Lamendola, Tracey Mclaughlin, Gerald M Reaven, Markus Stuehlinger, Philip S TsaoAbstract:C heart disease (CHD), the major cause of morbidity and mortality in patients with type 2 diabetes, cannot be entirely explained by the presence of conventional risk factors. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase. Plasma ADMA concentrations have been shown to be elevated in animals and patients with hypercholesterolemia and atherosclerosis, and intracellular concentrations of ADMA are increased in regenerated endothelial cells after balloon injury in rabbits with alloxan-induced hyperglycemia. Thus, we hypothesized that increased plasma concentrations of ADMA, by inhibiting NO synthase, could play a role in the depressed endothelial cell-dependent vasodilator responses that have been described in patients with type 2 diabetes. Because endothelial dysfunction is an early event in the process of atherogenesis, we also hypothesized that plasma ADMA concentrations are elevated in hyperglycemic patients with type 2 diabetes, and could contribute to the accelerated atherogenesis in these persons. To begin evaluation of these hypotheses, we compared plasma ADMA concentrations in normal volunteers with those in patients with type 2 diabetes. • • • The study was approved by the Stanford Human Subjects Committee, and volunteers gave informed consent before entering the clinical research center. The study group consisted of 18 nonDiabetic subjects and 16 patients with type 2 diabetes. No patient with type 2 diabetes had received any pharmacologic treatment for type 2 diabetes within the past 4 weeks, and had no apparent Diabetic Complication. All participants had a normal physical examination, blood count, and chemical screening battery. Blood was drawn after an overnight fast, and plasma frozen at –70°C until thawed for measurement of plasma glucose and lipid concentrations as described previously. Plasma concentrations of ADMA and symmetric dimethylarginine (SDMA) in plasma were measured by high-performance liquid chromatography with precolumn derivatization with o-phthaldialdehyde using a modification of a previously described method. ADMA concentrations were calculated by comparing the ADMA/homoarginine ratio with standards of known concentrations. The recovery rate for ADMA was 85% and the intrasample variation was 4%. The detection limit of the assay was 0.1 M. Results are expressed as mean SE, and the statistical significance of differences between the 2 groups estimated by Student’s t test. Results in Table 1 show that the 2 groups to be compared were similar in terms of age, gender distribution, body mass index, and total and low-density lipoprotein cholesterol concentrations. By selection, plasma glucose concentrations were significantly (p 0.001) higher in patients with type 2 diabetes. In addition, plasma triglyceride concentrations were higher (p 0.02) and high-density lipoprotein cholesterol concentrations lower (p 0.005) in patients with type 2 diabetes. Importantly, low-density lipoprotein cholesterol concentrations were similar in the first 2 groups. Figure 1 shows the individual and mean ADMA concentrations of the 2 groups, and it can be seen that the ADMA concentrations were significantly higher (p 0. 01) in patients with type 2 diabetes (1.59 0.22 vs 0.69 0.04 mol/L, p 0.001). Also, the separation of the 2 groups was almost complete, with 14 of the 16 patients with type 2 diabetes having ADMA concentrations higher than all 18 normal volunteers. From the Stanford University School of Medicine, Stanford, California. This report was supported by Research Grants HL-08506, HL-58638, and RR-00070 from the National Institutes of Health, Bethesda, Maryland. Dr. Reaven’s address is: Division of Cardiovascular Medicine, Falk CVRC, Stanford Medical Center, 300 Pasteur Drive, Stanford, California 94305. E-mail: greaven@cvmed.stanford.edu. Manuscript received April 30, 2001; revised manuscript received and accepted July 17, 2001. TABLE 1 Baseline Characteristics of Normal Volunteers and Patients With Type 2 Diabetes