The initiation of sugar cataract formation by the aldose reductase catalyzed accumulation of sorbitol in diabetic rats, and its prevention by the administration of aldose reductase inhibitors at the onset or early stages of diabetes, has been well established. In contrast, the inhibition of sorbitol dehydrogenase by 4-[4-(N,N-dimethylsulfamoyl)piperazino]-2-hydroxymethylpyrimidine (SDI-1) has ...

This study examined the role of p38 mitogen-activated protein (MAP) kinase in transducing high glucose into deficits in nerve conduction velocity (NCV) that are characteristic of diabetic neuropathy. p38 activation and NCV were measured in streptozocin-induced diabetic rats treated with a p38 inhibitor, an aldose reductase inhibitor, and insulin. Dorsal ...

In contrast to earlier views, new data indicate that proinsulin C-peptide exerts important physiological effects and shows the characteristics of an endogenous peptide hormone. C-peptide in nanomolar concentrations binds specifically to cell membranes, probably to a G-protein coupled receptor. Ca(2+)- and MAP-kinase dependent signalling pathways are activated, resulting in stimulation ...

Diabetic polyneuropathy is the most common acquired diffuse disorder of the peripheral nervous system. It is generally assumed that insulin benefits human and experimental diabetic neuropathy indirectly by lowering glucose levels. Insulin also provides potent direct support of neurons and axons, and there is a possibility that abnormalities in direct ...

Sensory neurons in diabetes may be primarily targeted by diabetes and their involvement may account for prominent sensory loss and pain in diabetic patients. Previous studies demonstrating evidence of excessive polyol flux, microangiopathy, and oxidative stress involving sensory axons and ganglia have been joined by more recent work demonstrating altered ...

Both structural and functional differences between normal and diabetic nerve have been observed, in human patients and animal models. We hypothesize that these structural differences are quantifiable, morphologically and mechanically, with the ultimate aim of understanding the contribution of these differences to permanent nerve damage. The outer collagenous epineurial and ...

To explore the molecular abnormalities underlying the degeneration of the node of Ranvier, a characteristic aberration of type 1 diabetic neuropathy, we examined in type 1 BB/Wor and type 2 BBZDR/Wor rats changes in expression of key molecules that make up the nodal and paranodal apparatus of peripheral nerve. Their ...

[1-(3,5-Difluoro-4-hydroxyphenyl)-1H-pyrrol-3-yl]phenylmethanone (6) was synthesized as a putative bioisostere of the known aldose reductase (AR) inhibitor (3-benzoylpyrrol-1-yl)acetic acid (I). It was found that 6 is approximately 5 times more potent as an in vitro inhibitor of AR than I, with an IC(50) value in the submicromolar range. Furthermore, 6 showed considerable ...

We sought to develop and validate a standardized cutaneous nerve regeneration model and to define the rate of epidermal nerve fibre (ENF) regeneration first in healthy control subjects and then in neuropathic and neuropathy-free subjects with diabetes. Next, we assessed the effect of different factors on the rate of nerve ...

Sensory neuropathy is a prominent component of diabetic neuropathy. It is not entirely clear how diabetes influences skin innervation, and whether these changes are correlated with clinical signs and laboratory findings. To investigate these issues, we performed skin biopsies on the distal leg of 38 consecutive type 2 diabetic patients ...

The effect of passive smoking on levels of neurotrophin in tears was studied in normal subjects or patients with atopic keratoconjunctivitis (AKC). Basal levels of neurotrophins, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and NT-4, in tears were significantly higher in AKC patients than those in normal ...

OBJECTIVE: To investigate the auditory rehabilitative results achieved in five patients with cochlear implants (CIs) who subsequently received, due to poor results, auditory brainstem implants (ABIs). MATERIAL AND METHODS: Between April 1997 and March 2003, 37 patients (age range 14 months to 70 years) were fitted with ABIs in our ...

Dysfunction of the autonomic nervous system is a recognized complication of diabetes, ranging in severity from relatively minor sweating and pupillomotor abnormality to debilitating interference with cardiovascular, genitourinary, and alimentary dysfunction. Neuroaxonal dystrophy (NAD), a distinctive distal axonopathy involving terminal axons and synapses, represents the neuropathologic hallmark of diabetic sympathetic ...

In this study we examine the multifocal electroretinogram (mfERG) recorded from patients suffering from Leber's hereditary optic neuropathy (LHON), a degeneration of the ganglion cell and nerve fibre layers of the retina. We compared the mfERGs recorded from 11 patients with LHON, to those from 11 control subjects. The pattern ...

Galanin peptide in primary sensory neurons may confer analgesia following injury. Its presence in regenerative axon sprouts where pain may be initiated has not been examined. We examined very early outgrowth of peptidergic axon sprouts after sciatic nerve crush in mice with experimental streptozotocin-induced diabetes. Diabetic mice had a retarded ...

AIMS/HYPOTHESIS: Sensory neuropathy in diabetic patients frequently presents itself as progressive loss of thermal perception, while some patients describe concurrent spontaneous pain, allodynia or hyperalgesia. Diabetic rats develop thermal hypoalgesia and tactile allodynia by unknown mechanisms. We investigated whether sensory disorders in rats were related to glucose metabolism by aldose ...

AIMS/HYPOTHESIS: Poly(ADP-ribose) polymerase activation depletes NAD+ and high-energy phosphates, activates protein kinase C, and affects gene expression in various tissues. This study was designed to characterise the effects of the potent, orally active poly(ADP-ribose) polymerase inhibitor PJ34 in the Wistar rat model of early diabetic neuropathy. METHODS: Control and streptozotocin-diabetic ...

OBJECTIVE: Since patients with large-fibre neuropathy do not show abnormal body sway during stance, the hypothesis was tested that postural control is not impaired until myelinated fibres of medium size are affected. METHODS: In 22 diabetic neuropathic patients and 13 normals, we recorded: (1) body sway area (SA), (2) stretch ...

In the present study, the authors examined whether treating streptozotocin-induced diabetic rats with the combination of alpha-lipoic acid and fidarestat, an aldose reductase inhibitor, can promote the formation of dihydrolipoic acid in diabetic animals and thereby enhance the efficacy of alpha-lipoic acid as monotherapy toward preventing diabetic vascular and neural ...

Treatment with alpha-lipoic acid (LA) or evening primrose oil (EPO), individually, fails to prevent diabetes-induced changes in enteric nerves. Since synergy between these treatments has been reported, the aim was to investigate the effectiveness of combined LA/EPO treatment. LA and EPO were administered in the diet (approximately 80 and 200 ...

A simplified approach to subperiosteal midface lifting with suspension is described, which has been performed on 75 patients since 1986. In comparison with standard facelifting, this technique results in long-lasting vertical resuspension of ptotic midfacial tissues. To date there has been a high rate of patient satisfaction with no cases ...

BACKGROUND: As part of our ongoing studies concerning the efficacy of using topically applied medications to treat retinal and optic nerve diseases, we previously showed that insulin accumulated in the retina, optic nerve, and cerebrospinal fluid (CSF) following topical application. The purpose of this study was to investigate which route ...

Oxidative and nitrosative stress play a key role in the pathogenesis of diabetic neuropathy, but the mechanisms remain unidentified. Here we provide evidence that poly(ADP-ribose) polymerase (PARP) activation, a downstream effector of oxidant-induced DNA damage, is an obligatory step in functional and metabolic changes in the diabetic nerve. PARP-deficient (PARP(-/-)) ...

Diabetic neuropathy is associated with changes in the extracellular matrix of the perineurium, including thickening of the basement membrane of the perineurial cells. Peripheral vascular disease (PVD) is a common vascular condition that can occur in the absence or presence of diabetes. Thickening of the vascular basement membrane of the ...

OBJECTIVE: To examine the variations and the anatomical characteristics of the tendinous arch of pelvic fascia (TAPF), the tendinous arch of levator ani (TALA) and the obturator fascia (Ofa) that are important structures in paravaginal defect repair and their relations with important neurovascular structures. STUDY DESIGN: We carried our study ...

PURPOSE: To determine the incidence of sixth nerve palsy in a population-based study, with particular emphasis on associated coexisting medical conditions and to use these data to develop a management algorithm. DESIGN: Retrospective, population-based case series. PARTICIPANTS: All residents of Olmsted County, Minnesota, USA, diagnosed with sixth nerve palsy between ...

AIMS: To determine the effects of acute hyperglycaemia on anorectal motor and sensory function in patients with diabetes mellitus. METHODS: In eight patients with Type 1, and 10 patients with Type 2 diabetes anorectal motility and sensation were evaluated on separate days while the blood glucose concentration was stabilized at ...

PURPOSE: Corneal confocal microscopy is a reiterative, rapid, noninvasive in vivo clinical examination technique capable of imaging corneal nerve fibers. Nerve fiber tortuosity may indicate a degenerative and attempted regenerative response of nerve fibers to diabetes. The purpose of this study was to define alterations in the tortuosity of corneal ...

We have examined the role of chondroitin sulfate proteoglycans (CSPGs) and keratan sulfate proteoglycans (KSPGs) in directing mossy fiber (MF) outgrowth and regeneration in rat hippocampal slice cultures. MFs normally exhibit a very specific innervation pattern that is restricted to the stratum lucidum (SL). In addition, MFs in hippocampal slice ...

Aberrations in nitrergic neurotransmission, due to a decrease in neuronal nitric oxide (NO) synthase (nNOS) protein, play an important role in the pathogenesis of autonomic neuropathy in diabetes. Until recently the mechanism of the decrease in nNOS protein content in nitrergic nerves during diabetes was debated. Two different views were ...

Diabetes mellitus is a common cause of peripheral nervous system disorders that manifest in a variety of clinical forms, many of which are often misdiagnosed. Over the past two decades, our understanding of the pathophysiology of diabetic nerve injury has improved remarkably through the elucidation of the important roles of ...

Connecting peptide (C-peptide) is secreted along with insulin in equimolar amounts into portal circulation in response to beta cell stimulation. The biological function of C-peptide had been mostly limited to establishing the secondary and tertiary structure of proinsulin. Recent studies have suggested that C-peptide can impact several functions, such as ...

Taurine is a semiessential amino acid, and its deficiency is involved in retinal and cardiac degenerations. In recent years, it was found that diabetes mellitus (DM) is associated with taurine, and many in vivo experimental studies showed that taurine administration is able to reduce the alterations induced by DM in ...

Nerve regeneration in diabetes is essential for reversal of neuropathy as well as the recovery of nerves from injury due to acute nerve compression and entrapment. Endoneural hypoxia due to hyperglycemia-induced blood flow reductions is observed early in the course of diabetes, and the resultant ischemia plays a role in ...

Na+,K(+)-ATPase is an ubiquitous membrane enzyme that allows the extrusion of three sodium ions from the cell and two potassium ions from the extracellular fluid. Its activity is decreased in many tissues of streptozotocin-induced diabetic animals. This impairment could be at least partly responsible for the development of diabetic complications. ...

The most common microvascular diabetic complication, diabetic peripheral polyneuropathy (DPN), affects type 1 diabetic patients more often and more severely. In recent decades, it has become increasingly clear that perpetuating pathogenetic mechanisms, molecular, functional, and structural changes and ultimately the clinical expression of DPN differ between the two major types ...

Peripheral diabetic neuropathy (PDN) affects up to 60% to 70% of diabetic patients, and is the leading cause of foot amputation. The pathogenesis of PDN involves multiple mechanisms. The findings obtained in 1999 to 2003 support the role of previously established mechanisms such as increased aldose reductase activity, nonenzymatic glycation ...

Symmetrical sensory polyneuropathy, the most common form of diabetic neuropathy in humans, is associated with a spectrum of structural changes in peripheral nerve that includes axonal degeneration, paranodal demyelination, and loss of myelinated fibers--the latter probably the result of a dying-back of distal axons. Mitochondrial dysfunction has recently been proposed ...

The accumulation of AGEs (advanced glycation end products) in diabetes mellitus has been implicated in the biochemical dysfunction associated with the chronic development of microvascular complications of diabetes--nephropathy, retinopathy and peripheral neuropathy. We investigated the concentrations of fructosyl-lysine and AGE residues in protein extracts of renal glomeruli, retina, peripheral nerve ...

BACKGROUND: Diabetes mellitus is associated with deficits in cerebral function. Vascular disorders may play a role in the pathogenesis and provide a potential target for treatment. The present study examined if prevention and intervention treatment with the angiotensin converting enzyme inhibitor enalapril could improve peripheral and central neurophysiological deficits in ...

It has been shown that alphaMSH and the nonmelanotropic ACTH/MSH(4-9) analog ORG 2766 can ameliorate cisplatin-induced neurotoxicity and ototoxicity. Here, we investigated whether these peptides delay the occurrence of the cisplatin-induced shift in auditory threshold, and whether they affect the subsequent recovery of cochlear potentials. Chronically implanted round window electrodes ...

Clinical and electroneuromyographic studies were performed in 121 patients with diabetic polyneuropathy (DPN) before and after courses of treatment with pulsed electromagnetic fields with complex modulation (PEMF-CM) at different frequencies (100 and 10 Hz). Testing of patients using the TSS and NIS LL scales demonstrated a correlation between the severity ...

Neuropathy is one of the most debilitating complications of both type 1 and type 2 diabetes, with estimates of prevalence between 50-90% depending on the means of detection. Diabetic neuropathies are heterogeneous and there is variable involvement of large myelinated fibers and small, thinly myelinated fibers. Many of the neuronal ...

Diabetic neuropathy is a common complication of diabetes mellitus patients. It is a wide range of abnormalities affecting proximal and distal peripheral sensory and motor nerves. Although plasma hyperosmolality is a common finding in diabetes mellitus, the effects of hyperosmolality on conduction of various sensory signal components have not been ...

Patients with complaints of numbness, tingling, and dysesthesias in the toes and feet are frequently referred to neurologists. Often, the only objective evidence for peripheral nerve dysfunction in these patients is limited to small-caliber sensory nerve fibers. On examination these patients may have reduced distal pinprick sensation, and distal leg ...

During treatment for type 2 diabetes with a diabetic diet (without medication), a 61-year-old Japanese man suddenly developed hyposmia. The fasting plasma glucose was 208 mg/dl and haemoglobin A1c was 8.6%. On investigation, there were no indications of disease of the brain, or the nasal or paranasal sinuses. The intravenous ...

The distinction between metabolic and structural changes occurring in autonomic neurons during diabetes has not been fully clarified. Here we demonstrate that nitric oxide synthase-containing (nitrergic) neurons innervating the penis and gastric pylorus of streptozotocin-induced diabetic rats undergo a selective degenerative process in two phases. In the first phase, nitrergic ...

BACKGROUND AND OBJECTIVES: Nerve stimulation is a useful technique to identify peripheral nerves before blockade. We report 2 cases of the failure of nerve stimulation to accurately localize the sciatic nerve in patients with diabetes mellitus undergoing outpatient foot procedures. We also introduce a novel approach to performing a popliteal ...

Elevated plasma lipids contribute to neurovascular dysfunction in diabetes. Statins have lipid-lowering properties and can modulate endothelial nitric oxide (NO) bioavailability. The aim was to assess the impact of these factors on autonomic nitrergic nerve and endothelial function. Thus, the effects of diabetes and treatment with the HMG-CoA reductase inhibitor ...

Diabetic polyneuropathy (DPN) is the most common chronic complication of diabetes and affects Type 1 diabetic patients disproportionately. In the last two decades it has become increasingly evident that underlying metabolic, molecular and functional mechanisms and, ultimately, structural changes differ in DPN between the two major types of diabetes. In ...