Long-term experimental diabetes may best model the prominent and irreversible sensory deficits of chronic human diabetic polyneuropathy. Whereas irretrievable loss of sensory neurons, if present, would be an unfortunate feature of the disease, systematic unbiased counting has indicated that sensory neurons survive long-term experimental diabetes. In this study, we examined ...

Upregulation of vascular NAD(P)H oxidase has been considered an important source for elevated levels of reactive oxygen species that contribute to several cardiovascular disease states, including the vascular complications of diabetes mellitus. Previous studies have shown that treatment with antioxidants corrects impaired nerve function and blood flow in diabetic rats. ...

Increased activity of the beta-isoform of protein kinase C (PKC) has been linked to the vascular and neural complications of diabetes mellitus. Treatment with the PKCbeta inhibitor, (s)-13-[(dimethylamino)methyl]-10,11,14,15-tetrahydro-4,9:16,21-dimetheno-1H,13H-dibenzo[e,k]pyrrolo[3,4-h][1,4,13]oxadiazacyclohexadecene-1,3(2H)-dione, (LY333531), improves somatic nerve function and blood flow in diabetic rats. The aim was to assess whether LY333531 treatment could prevent nitric ...

OBJECTIVE: The purpose of this study was to determine the changes in the amplitudes of a sensory nerve action potential (NAP) to a conditioning stimulus given prior to a test stimulus at 2-8 ms intervals in healthy subjects and patients with diabetes mellitus with no clinical signs of neuropathy and ...

To further understand the role of aldose reductase (AR) in the etiology of diabetic neuropathy, we generated transgenic mice that overexpress AR specifically in the Schwann cells under the control of the rat myelin protein zero (P0) promoter. One of the transgenic mouse lines, which has overexpression of AR mRNA ...

We report a patient with Type 2 diabetes mellitus complicated by neuropathy affecting the phrenic nerves, resulting in fatal respiratory failure. Diabetic mononeuropathy is common and usually recovers spontaneously, but bilateral phrenic nerve involvement appears to be uncommon and difficult to treat. The pathology of diabetic mononeuropathy is not well ...

Vascular defects contribute substantially to neuropathic changes associated with metabolic abnormalities in diabetes. Statins appear to exert beneficial effects on vascular function independent of cholesterol lowering. In studies of the streptozotocin-induced diabetes rat model, rosuvastatin treatment was shown to correct sciatic motor and saphenous sensory nerve conduction velocity deficits (large ...

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, ...

Proinsulin C-peptide treatment can partially prevent nerve dysfunction in type 1 diabetic rats and patients. This could be due to a direct action on nerve fibers or via vascular mechanisms as C-peptide stimulates the nitric oxide (NO) system and NO-mediated vasodilation could potentially account for any beneficial C-peptide effects. To ...

Ulnar neuropathy in the forearm is an unusual cause of hand weakness and sensory loss that is most often attributed to compression of the nerve distally within the humero-ulnar arcade (cubital tunnel). An association with diabetes mellitus, however, has not been reported. We identified four patients with type I diabetes ...

The tetrodotoxin-resistant sodium channel alpha subunit, Nav1.8, is exclusively expressed in primary sensory neurons and is suggested to play a role in the generation of ectopic action potentials after axonal injury and thereby contribute to neuropathic pain. Here we investigated the involvement of Nav1.8 in ectopic impulse generation in damaged ...

OBJECTIVE: Our aims were to better understand the mechanisms underlying peripheral neuropathy with diabetes mellitus and to test the hypothesis that acute lowering of glucose levels induces apoptosis in hypoxic neurons. METHODS: We used rat dissociated dorsal root ganglion (DRG) neurons incubated in a medium high in glucose concentration (700 ...

Four patients with type 2 diabetes mellitus developed mononeuritis multiplex subacutely. Sural nerve biopsies showed multifocal axonal loss in all patients, with epineurial perivascular inflammation affecting small calibre vessels in three. Three patients improved with immunotherapy. These observations suggest that mononeuritis multiplex in diabetes may be caused by an immune ...

It is known that diabetic neuropathy is the result of endoneurial edema caused by various biochemical reactions triggered by hyperglycemia. This sequence of events can cause cessation of circulation at the perineurial level, or the tough layer, which is not resilient enough to spread intraneural pressure. Internal and external limiting ...

Poly-(R)-3-hydroxybutyrate, a linear polymer of the ketone body, R-3-hydroxybutyric acid, is an amphiphilic, water-insoluble, salt-solvating polymer. In humans, shortchain, complexed polyhydroxybutyrate has been found in a wide variety of tissues and in atherosclerotic plaques. In the circulation, plasma polyhydroxybutyrate concentrations correlate strongly with atherogenic lipid profiles. We compared polyhydroxybutyrate levels ...

Neurogenic positional pedal neuritis is a presentation of neuritic symptoms in one or both feet usually affected by body position, specifically, the position of the spine. Its etiology is similar to that of neurogenic-induced claudication caused by spinal stenosis in that the symptoms are caused by compression or irritation of ...

AIMS/HYPOTHESIS: The accurate detection, characterization and quantification of human diabetic neuropathy are important to define at risk patients, anticipate deterioration, and assess new therapies. Corneal confocal microscopy is a reiterative, rapid, non-invasive in vivo clinical examination technique capable of imaging corneal nerve fibres. The aim of this study was to ...

OBJECTIVE: To report on the value of interdigital nerve (IDN) conduction study (NCS) of the foot for the recognition of diabetic sensory polyneuropathy with normal routine NCS and the nature of electrophysiological abnormality in early diabetic sensory polyneuropathy. METHODS: The sensory nerve conductions in the two digital and 4 IDNs ...

The objective was to determine whether stress-activated protein kinases (SAPKs) mediated the transfer of diabetes-induced stress signals from the periphery to somata of sensory neurons. Thus, we characterized axonal transport of SAPKs in peripheral nerve, studied any alteration in streptozotocin (STZ)-diabetic rats and examined effects of neurotrophin-3 (NT-3) on diabetes-induced ...

Chronic hydrocephalus that begins in childhood and progresses only very gradually is sometimes called "arrested" hydrocephalus. Data suggest that this state eventually can become symptomatic and may be treatable by shunting. However, the pathological substrate of the disorder is not entirely understood. We studied chronic hydrocephalus in rats, 9 months ...

This study aimed to show ultrastructural effects of diabetes and cadmium on the optic nerve. We used 52 healthy Swiss albino male rats. They were divided into four groups: control (C), diabetic (D), cadmium, (Cd), and diabetic with cadmium (D + Cd). The diabetic condition was created by intravenous injection ...

Diabetic neuropathy is the most common peripheral neuropathy in western countries. Although every effort has been made to clarify the pathogenic mechanism of diabetic neuropathy, thereby devising its ideal therapeutic drugs, neither convinced hypotheses nor unequivocally effective drugs have been established. In view of the pathologic basis for the treatment ...

The structure of the central and peripheral nervous systems was studied. in the C57BL/6Akita (Akita) mouse, a non-obese type 2 diabetes model characterized by early onset, autosomal dominant inheritance and a mutation of the insulin 2 gene. Usual neuropathological examinations showed no remarkable abnormalities in the brain, spinal cord or ...

OBJECTIVE: To measure the conduction velocity, absolute refractory period and duration of the action potential for individual afferents of the median nerve in diabetic patients and to examine correlations between measures and with temperature and compare this to data from normal subjects. METHODS: The technique of percutaneous microneurography was used ...

AIM/HYPOTHESIS: Diabetic neuropathy is accompanied by a range of positive (paresthaesia, dysesthaesia, pain) and negative (hypesthaesia, anesthaesia) neurological symptoms suggesting widespread alterations in axonal excitability. The nature and the mechanisms underlying these alterations in axonal excitability are not well understood. The aim of this study was to examine the extent ...

Hedgehog proteins modulate development and patterning of the embryonic nervous system. As expression of desert hedgehog and the hedgehog receptor, patched-1, persist in the postnatal and adult peripheral nerves, the hedgehog pathway may have a role in maturation and maintenance of the peripheral nervous system in normal and disease states. ...

Composite scores may be more sensitive and reproducible than single attributes of nerve conduction for detection of peripheral neuropathy, but this requires validation in large patient cohorts. Also, the concordance of individual attributes versus composite scores with clinical measures of severity has not been tested. Here, we study these issues ...

Mechanical hyperalgesia is an early symptom of diabetic neuropathy. To evaluate the mechanisms underlying this symptom, it was studied and compared in rat models of systemic and local hyperglycemia. Systemic hyperglycemia was induced by a single injection of streptozotocin (STZ, 50 mg/kg). Local hyperglycemia either in L(5) dorsal root ganglion ...

Several functional properties of Na,K-ATPase are strongly dependent on membrane fatty acid composition, but the underlying mechanism is still not well defined. We have studied the effects of two types of supplementations enriched in the w3 polyunsaturated fatty acids on the Na,K-ATPase and Mg-ATPase activities in sciatic nerve (SN) and ...

A great variety of alterations have been described in the nervous system of diabetic animals. They are named as diabetic neuropathy and affect the brain, spinal cord and peripheral nerves. In diabetic animals, plasma and tissue catecholamine levels have been reported to be increased, decreased or unchanged, and these disparities ...

We compared the development of sciatic nerve neuropathy in young diabetic rats with that in non-diabetic aged rats. Diabetes was induced in six-month old rats by injection with alloxan and was moderately controlled by single daily injections of insulin. Blood insulin levels in diabetic rats were significantly reduced compared to ...

Nerve conduction studies performed between 1994 and 1996 on the median nerves of 204 hands of 113 patients [20 patients in hemodialysis (HD) with diabetic nephropathy, 27 without diabetes mellitus in HD for 10 years or more, 18 without diabetes mellitus in HD for less than 10 years, and 48 ...

Sensory neuropathy is common symptom of the diabetes mellitus and the prevalence of oral lesions is higher in diabetic patients. The distribution of substance P was studied immunohistochemically in streptozotocin induced diabetic rat's tongue. The morphological association of sensory nerves (substance P immunoreactive) with mast cells (nerve fibre-mast cell contact) ...

BACKGROUND: Myo-inositol plays a key role in an important intracellular signalling pathway. A deranged myo-inositol metabolism has been associated with neural tube defects. A myo-inositol loading test was performed to investigate the kinetics in healthy women of reproductive age. METHODS: Five healthy non-obese females [mean age (standard deviation: SD) 22.8 ...

The aim of the study was to investigate antioxidant (alpha-lipoic acid [LA]) and gamma-linolenic acid treatments in the prevention of changes in autonomic nerves induced in streptozotocin-diabetic rats. Autonomic nerves supplying the heart, penis, and gut were examined using immunohistochemical and biochemical techniques. LA and gamma-linolenic acid (present in evening ...

BACKGROUND: Peripheral neuropathy commonly develops in patients with advanced chronic renal failure. The uremic neuropathy is often subclinical and detectable only by electrophysiological studies. Receptors to erythropoietin (EPO) have been described on non-hematopoietic cells including neuronal cells. METHODS: In order to evaluate the effect of five months' EPO therapy on ...

OBJECTIVE: To explore the role of insulin-like growth factor 1 (IGF-1) gene expression abnormality in neurotrophic causes of diabetic peripheral neurophathy. METHODS: Diabetes was induced in Sprague Dawley rats by alloxan. The parameters were measured as follows: IGF-1 mRNA by revere transcriptase-polymer chain reaction (RT-PCR); IGF-1 peptide by enzyme-linked immunosorbent ...

Diabetes is known to activate MAP kinase p38 in sensory neurons in both rats and patients. In vitro, activation of p38 in sensory neurons by combined glucose and oxidant stress causes cell damage or death. Consequently we tested the hypothesis that inhibition of MAP kinase p38 might prevent neuronal dysfunction ...

OBJECTIVE: The aim of the current study was to determine the validity of the Toronto Clinical Scoring System (CSS) in reflecting the presence and severity of diabetic peripheral sensorimotor polyneuropathy (DSP) as determined by myelinated fiber density (FD) on sural nerve biopsy. RESEARCH DESIGN AND METHODS: Eighty-nine patients with both ...

Peripheral neuropathy is a serious diabetic complication. Delayed nerve regeneration in diabetic animal models suggests abnormalities in proliferation/differentiation of Schwann cells (SC). We recently reported that endothelins (ETs) regulate proliferation and phenotype in primary and immortalized SC (iSC). We now investigated changes in the effects of ETs on SC proliferation ...

Nutritional supplementation with dehydroepiandrosterone (DHEA) may be a candidate for treating diabetes-induced vascular and neural dysfunction. DHEA is a naturally occurring adrenal androgen that has antioxidant properties and is reportedly reduced in diabetes. Using a prevention protocol, we found that dietary supplementation of streptozotocin-induced diabetic rats with 0.1, 0.25, or ...

In this study, neurological complications associated with spontaneously occurring feline diabetes were comprehensively evaluated. Physical and neurological examinations, electrophysiological assessment, and biochemical and histological analysis of nerve and muscle biopsy specimens were performed in 19 diabetic cats and referenced to similar data from 28 nondiabetic cats without evidence of neuropathy. ...

We have previously suggested that alterations in sequential early gene responses of trophic factors (IGF-1 -->c-fos-->NGF) contribute to impaired peripheral nerve regeneration in type 1 diabetic BB/W-rats. To study the role these responses may play in type 2 diabetic nerve regeneration, BB/Z-rats were subjected to sciatic nerve crush injury. The ...

We report here a novel sorbitol dehydrogenase inhibitor, 16, that shows very high oral potency (50 microg/kg) in normalizing elevated fructose levels in the sciatic nerve of chronically diabetic rats and sustained duration of action (>24 h). Furthermore, 16 shows attractive pharmaceutical properties, including good solubility in simulated human gastric ...

PURPOSE It has been proposed that a deficiency in the axonal transport of nerve growth factor (NGF) may have an important role in inducing diabetic neuropathy, which contributes to diabetic cystopathy. Therefore, in streptozotocin (Sigma Chemical Co., St. Louis, Missouri) induced diabetic rats we investigated the relationship of bladder function ...

BACKGROUND: The transition metal-catalyzed reaction is a major source of oxygen free radicals, which play an important role in vascular dysfunction leading to ischemia in diabetic tissues. The inhibition of polyol pathway hyperactivity has been reported to ameliorate neurovascular abnormalities in diabetic rats and has been proposed to improve the ...

Elevated protein kinase C activity has been linked to the vascular and neural complications of diabetes. The aim of the present study was to examine the involvement of the beta-isoform of protein kinase C in abnormalities of neuronal function, neural tissue perfusion and endothelium-dependent vasodilation in diabetes, by treatment with ...

This study investigated the time-course of the nociceptive neuropeptide substance P and nerve growth factor (NGF), which facilitates substance P production, in lumbar and cervical dorsal root ganglia (DRG) of streptozotocin-induced diabetic rats. Levels of substance P and NGF were measured by radioimmunoassay and sandwich enzyme-linked immunosorbent assay, respectively, 2 ...

The present study was performed to determine whether nitric oxide overproduction is associated with deterioration in peripheral nerve function in type 1 diabetes. We measured peripheral nerve function and biochemical indicators of nitrosative stress annually for 3 years in 37 patients with type 1 diabetes. Plasma nitrite and nitrate (collectively ...

AIM: While the mechanism in the pathogenesis of diabetic corneal disease is unclear, aldose reductase has been implicated in corneal disease. The effects of an oral aldose reductase inhibitor (ARI) on the ocular surface of diabetic patients after cataract surgery were studied. METHODS: This clinical trial was designed to be ...