26 research outputs found
Update on the management of diabetic polyneuropathies
The prevalence of diabetic polyneuropathy (DPN) can approach 50% in subjects with longer-duration diabetes. The most common neuropathies are generalized symmetrical chronic sensorimotor polyneuropathy and autonomic neuropathy. It is important to recognize that 50% of subjects with DPN may have no symptoms and only careful clinical examination may reveal the diagnosis. DPN, especially painful diabetic peripheral neuropathy, is associated with poor quality of life. Although there is a better understanding of the pathophysiology of DPN and the mechanisms of pain, treatment remains challenging and is limited by variable efficacy and side effects of therapies. Intensification of glycemic control remains the cornerstone for the prevention or delay of DPN but optimization of other traditional cardiovascular risk factors may also be of benefit. The management of DPN relies on its early recognition and needs to be individually based on comorbidities and tolerability to medications. To date, most pharmacological strategies focus upon symptom control. In the management of pain, tricyclic antidepressants, selective serotonin noradrenaline reuptake inhibitors, and anticonvulsants alone or in combination are current first-line therapies followed by use of opiates. Topical agents may offer symptomatic relief in some patients. Disease-modifying agents are still in development and to date, antioxidant α-lipoic acid has shown the most promising effect. Further development and testing of therapies based upon improved understanding of the complex pathophysiology of this common and disabling complication is urgently required
Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications
Superparamagnetic iron oxide nanoparticles
can providemultiple benefits for biomedical applications
in aqueous environments such asmagnetic separation or
magnetic resonance imaging. To increase the colloidal
stability and allow subsequent reactions, the introduction
of hydrophilic functional groups onto the particles’
surface is essential. During this process, the original
coating is exchanged by preferably covalently bonded
ligands such as trialkoxysilanes. The duration of the
silane exchange reaction, which commonly takes more
than 24 h, is an important drawback for this approach. In
this paper, we present a novel method, which introduces
ultrasonication as an energy source to dramatically
accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove
the generic character, different functional groups were
introduced on the surface including polyethylene glycol
chains, carboxylic acid, amine, and thiol groups. Their
colloidal stability in various aqueous buffer solutions as
well as human plasma and serum was investigated to
allow implementation in biomedical and sensing
applications.status: publishe
Update on the management of diabetic polyneuropathies
Jayadave Shakher1, Martin J Stevens1,21Heart of England NHS Foundation Trust, Birmingham, UK; 2School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UKAbstract: The prevalence of diabetic polyneuropathy (DPN) can approach 50% in subjects with longer-duration diabetes. The most common neuropathies are generalized symmetrical chronic sensorimotor polyneuropathy and autonomic neuropathy. It is important to recognize that 50% of subjects with DPN may have no symptoms and only careful clinical examination may reveal the diagnosis. DPN, especially painful diabetic peripheral neuropathy, is associated with poor quality of life. Although there is a better understanding of the pathophysiology of DPN and the mechanisms of pain, treatment remains challenging and is limited by variable efficacy and side effects of therapies. Intensification of glycemic control remains the cornerstone for the prevention or delay of DPN but optimization of other traditional cardiovascular risk factors may also be of benefit. The management of DPN relies on its early recognition and needs to be individually based on comorbidities and tolerability to medications. To date, most pharmacological strategies focus upon symptom control. In the management of pain, tricyclic antidepressants, selective serotonin noradrenaline reuptake inhibitors, and anticonvulsants alone or in combination are current first-line therapies followed by use of opiates. Topical agents may offer symptomatic relief in some patients. Disease-modifying agents are still in development and to date, antioxidant α-lipoic acid has shown the most promising effect. Further development and testing of therapies based upon improved understanding of the complex pathophysiology of this common and disabling complication is urgently required.Keywords: diabetes, neuropathic pain, microvascular, glucose&nbsp
Effects of a synthetic retinoid on skin structure, matrix metalloproteinases, and procollagen in healthy and high-risk subjects with diabetes
BACKGROUND: In diabetes foot ulceration may result from increased skin fragility. Retinoids can reverse some diabetes-induced deficits of skin structure and function but their clinical utility is limited by skin irritation. The effect of diabetes and MDI 301 a non-irritating synthetic retinoid and retinoic acid have been evaluated on matrix metalloproteinases (MMPs), procollagen expression and skin structure in skin biopsies from non-diabetic volunteers and diabetic subjects at risk of foot ulceration using organ culture techniques. METHODS: Zymography and ELISA were utilized for analysis of MMP-1,-2,-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) and immunohistochemisty for type I procollagen protein abundance. Collagen structure parameters were assessed in formalin-fixed, paraffin-embedded tissue sections. RESULTS: The % of active MMP-1 and -9 was higher and TIMP-1 abundance lower in subjects with diabetes. Type 1 procollagen abundance was reduced and skin structural deficits were increased in diabetes. Three ÎĽm MDI 301 reduced active MMP-1 and -9 abundance by 29% (p<0.05) and 40% (p<0.05), respectively and increased TIMP-1 by 45% (p=0.07). MDI 301 increased type 1 procollagen abundance by 40% (p<0.01) and completely corrected structural deficit scores. Two ÎĽm retinoic acid reduced MMP-1 but did not significantly affect skin structure. CONCLUSIONS: These data indicate that diabetic patients at risk of foot ulceration have deficits of skin structure and function. MDI 301 offers potential for repairing this skin damage complicating diabetes