Diabetic neuropathies

Stracke, H., Meyer, U., Schumacher, H., Federlin, K.. Mexilitine in the treatment of diabetic neuropathy, Diabetes Care 1992, 15, 1550-1555. 

Hepburn DA, MacLeod KM, Frier BM. Physiological, symptomatic and hormonal responses to acute hypoglycae-mia in type 1 diabetic patients with autonomic neuropathy. Diabet Med 1993 10(10) 940-9. 

Neumann C, Martinez D, Schmid H. Nocturnal oxygen desaturation in diabetic patients with severe autonomic neuropathy. Diabetes Res Clin Pract 1995 28 97-102. 

The participation of aldose reductase in the development of diabetic complications is assumed to be based on a triad of tissue effects sorbitol accumulation, myo-inositol depletion and decreased activity of Na/K-ATPase. These alterations, first described in the ocular lens, also occur in other tissues like the renal glomerulus, peripheral nerves and the retina. The enhanced activity of aldose reductase may therefore be involved in the development of diabetic neuropathy, diabetic retinopathy and diabetic nephropathy, although it may not be the sole factor underlying these complications. 

Sensory function Touch patient on both arms/legs and assess symmetry inquire about paresthesias. Stroke, neuropathy (diabetes, HIV, drug-induced)... 

Thomas PK, Tomlinson DR. 1999. Diabetic and hypoglycemic neuropathy. Diabetic Neuropathy Dyck PJ, Thomas PK, editors. 2nd ed, Elsevier, pp. 1219-1250. 

Nagamatsu M, Nickander KK, Schmelzer JD, Raya A, Wittrock DA, TritschlerH, et al. Lipoic acid improves nerve blood flow, reduces oxidative stress, and improves distal nerve conduction in experimental diabetic neuropathy. Diabetes Care 1995 18 1160-1167. 

Uccioli, L., P.G. Giacomini, G. Monti cone, A. Magrini, L. Durola, E. Bruno, L. Parisi, S. Di Girolamo, and G. Menzinger. 1995. Body sway in diabetic neuropathy. Diabetes Care 18(3) 339-344. 

Dejgaard A. Pathophysiology and treatment of diabetic neuropathy. Diabet Med 1988 15 97-112. 

Hotta N, Akanuma Y, Kawamori R et al. Long-term clinical effects of Epakestat, an aldose reductase inhibitor, on diabetic peripheral neuropathy. Diabetes Care 2006 29(7) 1538-1544. 

Boulton AJM, Vinik At, Arezo JC et al. Diabetic neuropathies. Diabetes Care 2005 28(4) 956-962. 

Arora, S., Smakowski, Fryberg, R.G., Simone, L.R, Freeman, R, Logerfo, F.W., and Veves, A., Differences in foot and forearm skin microcirculation in diabetic patients with and without neuropathy. Diabetes Care, 1998, 21, 1339-1344. 

The Capsaicin Study Group (1992) Effect of treatment with capsaicin on daily activities of patients with painful diabetic neuropathy. Diabet Care 15 159-165 Derry S, Lloyd R, Moore RA, McQuay HJ (2009) Topical capsaicin for chronic neuropathic pain in adults (Review). Cochrane Database Syst Rev, Issue 4. Art. No. CD007393 Glinski W, Glinska-Ferenz M, Pierozynska-Dubowska M (1991) Neurogtmic inflammation induced by capsaicin in patients with psoriasis. Acta Derm Venereol 71 51-54 Arnold WP, van de Kerkhof PC (1993) Topical capsaicin in pruritic psoriasis. J Am Acad Dermatol 29 438 142... 

Vignette 12. Treatable forms of "diabetic neuropathy" diabetes-2 dysimmune sensory-motor polyneuropathy, and genetico-diabetoid-2 dysimmune polyneuropathy... 

Used in treatment of diabetic neuropathy and retinopathy ponalrestat [72702-95-5] C2yH22BrFN202... 

Tolrestat (28) is a long-acang aldose reductase inhibitor useful in the prophylaxis of diabetic neuropathy, retinopathy, and cataracts [24 25] Lastly, the intro-ducuon of fluorine into steroids probably ushered in the modem era of fluonnated drugs Many commercial products were introduced [2] Typical of the products are the anti inflammatory glucocorticoids dexamethasone (29 X = F, Y = H), para-methasone (29, X = H, Y = F), and flumethasone (29, X = H, Y = F)... 

Association of Pain, neuropathic pain is defined as pain initiated or caused by a primary lesion, dysfunction in the nervous system". Neuropathy can be divided broadly into peripheral and central neuropathic pain, depending on whether the primary lesion or dysfunction is situated in the peripheral or central nervous system. In the periphery, neuropathic pain can result from disease or inflammatory states that affect peripheral nerves (e.g. diabetes mellitus, herpes zoster, HIV) or alternatively due to neuroma formation (amputation, nerve transection), nerve compression (e.g. tumours, entrapment) or other injuries (e.g. nerve crush, trauma). Central pain syndromes, on the other hand, result from alterations in different regions of the brain or the spinal cord. Examples include tumour or trauma affecting particular CNS structures (e.g. brainstem and thalamus) or spinal cord injury. Both the symptoms and origins of neuropathic pain are extremely diverse. Due to this variability, neuropathic pain syndromes are often difficult to treat. Some of the clinical symptoms associated with this condition include spontaneous pain, tactile allodynia (touch-evoked pain), hyperalgesia (enhanced responses to a painful stimulus) and sensory deficits. 

Rice bran is the richest natural source of B-complex vitamins. Considerable amounts of thiamin (Bl), riboflavin (B2), niacin (B3), pantothenic acid (B5) and pyridoxin (B6) are available in rice bran (Table 17.1). Thiamin (Bl) is central to carbohydrate metabolism and kreb s cycle function. Niacin (B3) also plays a key role in carbohydrate metabolism for the synthesis of GTF (Glucose Tolerance Factor). As a pre-cursor to NAD (nicotinamide adenine dinucleotide-oxidized form), it is an important metabolite concerned with intracellular energy production. It prevents the depletion of NAD in the pancreatic beta cells. It also promotes healthy cholesterol levels not only by decreasing LDL-C but also by improving HDL-C. It is the safest nutritional approach to normalizing cholesterol levels. Pyridoxine (B6) helps to regulate blood glucose levels, prevents peripheral neuropathy in diabetics and improves the immune function. 

In diabetic rats, TRPVl is enhanced on myelinated fibres and is hyperphos-phorylated by PKC [127]. In accordance with these findings, anti-TRPVl antiserum was shown to ameliorate pain in a murine model of diabetic neuropathy [128]. In humans, the density of TRPVl-positive nerve fibres is increased in women with chronic breast pain [129] and with vulvodynia [19]. Disruption of TRPV 1 gene causes attenuation of bone cancer pain in mice [130]. Pharmacological blockade of TRPVl by agonists relieved pain in AIDS patients [131]. 

Risk factors that may increase the potential for hypotension include elderly age, diabetes, autonomic neuropathy, uremia, and cardiac disease.46 The symptoms associated with hypotension during dialysis include dizziness, nausea, vomiting, sweating, and chest pain. 

Neuropathic pain is defined as spontaneous pain and hypersensitivity to pain associated with damage to or pathologic changes in the peripheral nervous system as in painful diabetic peripheral neuropathy (DPN), acquired immunodeficiency syndrome (AIDS), polyneuropathy, post-herpetic neuralgia (PHN) or pain originating in the central nervous system (CNS), that which occurs with spinal cord injury, multiple sclerosis, and stroke. Functional pain, a relatively newer concept, is pain sensitivity due to an abnormal processing or function of the central nervous system in response to normal stimuli. Several conditions considered to have this abnormal sensitivity or hyperresponsiveness include fibromyalgia and irritable bowel syndrome. 

DPN, diabetic peripheral neuropathy PHN, post-herpetic neuralgia TCA, tricyclic antidepressant. 

Owing to the lag time between initiation and effect, capsaicin is not used for treatment of acute pain from injury. Instead, topical capsaicin is used for chronic pain from musculoskeletal and neuropathic disorders. Capsaicin preparations have been studied in the treatment of pain from diabetic neuropathy, osteoarthritis, rheumatoid arthritis, postherpetic neuralgia, and other disorders.48 It is often used as an adjuvant to systemic analgesics in these chronic pain conditions. 

The pathogenesis of diabetic foot infection stems from three key factors neuropathy, angiopathy, and immunopathy. Aerobic gram-positive cocci, such as S. aureus and P-hemolytic streptococci, are the predominant pathogens in acutely infected diabetic foot ulcers. However, chronically infected wounds are subject to polymicrobial infection and require treatment with broad-spectrum antibiotics. 

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