Decrease In Motor Nerve Conduction Velocity Research Articles

Effects of organophosphate phenyl saligenin phosphate and polyether carboxylic ionophore lasalocid on motor nerve conduction velocity, neuropathy target esterase enzyme activity, and clinical ataxia in chickens

Organophosphates (OP) are widely used chemicals in agriculture and industry. Some OPs produce a delayed type of neuropathy affecting human and animals following exposure. Subacute neurotoxic doses of some OPs can be potentiated by concomitant exposure to certain chemicals. Lasalocid is a polyether carboxylic ionophore used as a growth promotant and anti-coccidial in the cattle and poultry industries, respectively. Lasalocid is also known to induce peripheral neuropathy. Neurotoxicity of phenyl saligenin phosphate (PSP) and lasalocid and possible interaction were studied in chickens by evaluating motor nerve conduction velocity (MNCV), clinical ataxia, and neuropathy target esterase (NTE) enzyme activity. Forty-eight fryer chickens were divided into four groups as follows: Group 1 (control), group 2 was injected with single subcutaneous (s.c.) PSP (5 mg/kg), group 3 received oral lasalocid sodium (20 mg/kg, b.i.d., for 2 days), and group 4 received single s.c. PSP injection plus oral lasalocid sodium. MNCVs were decreased in groups 2, 3, and 4 compared to control. While there was no difference in MNCV between groups 2 and 3 (p > 0.05), MNCV in group 4 were significantly lower than in groups 2 and 3 (p < 0.05). NTE activities were significantly lower in PSP and PSP+lasalocid groups than in control and lasalocid group (p < 0.05). Onset of ataxia in group 4 appeared early and was exacerbated compared to groups 2 and 3. In conclusion, PSP and lasalocid could induce a significant decrease in MNCV and produce ataxia. Neuropathic OPs could be exacerbated by polyether ionophore lasalocid.

Improvement of Motor Nerve Conduction Velocity in Diabetic Rats Requires Normalization of the Polyol Pathway Metabolites Flux

Using ranirestat, an aldose reductase (AR) inhibitor, we investigated the relationship between sorbitol and fructose levels in the sciatic nerve and motor nerve conduction velocity (MNCV) in streptozotocin (STZ)-treated diabetic rats. Ranirestat inhibited rat and recombinant human AR with similar IC50 values and equipotently prevented sorbitol accumulation in rat erythrocytes and sciatic nerves in vitro. One week after STZ administration, sorbitol levels in rat erythrocytes and sciatic nerves significantly increased while MNCV decreased. Oral administration of ranirestat (0.03 – 1.0 mg/kg per day) for 3 weeks dose-dependently decreased the elevated sorbitol and fructose levels in the rat sciatic nerves without affecting blood glucose level. Particularly, at doses of 0.1 mg/kg per day or higher, ranirestat normalized both sorbitol and fructose levels in the sciatic nerves of STZ-treated rats. Ranirestat (0.1 – 1.0 mg/kg per day) also improved the STZ-induced decrease in MNCV in a dose-dependent manner. This improvement correlated with the decrease of sorbitol and fructose levels in the rat sciatic nerves. These findings indicate that ranirestat improves MNCV via normalization of sorbitol and fructose accumulation in the sciatic nerve.

Ranirestat (AS-3201), a Potent Aldose Reductase Inhibitor, Reduces Sorbitol Levels and Improves Motor Nerve Conduction Velocity in Streptozotocin-Diabetic Rats

Ranirestat (AS-3201) is a novel aldose reductase (AR) inhibitor with potentially beneficial effects on diabetic sensorimotor polyneuropathy. In this study, we performed a kinetic analysis to determine the mode of inhibition of ranirestat on AR and investigated the effects of ranirestat on sorbitol levels in the sciatic nerves and lens of streptozotocin (STZ)-diabetic rats. We also evaluated the effects on motor nerve conduction velocity (MNCV) in STZ-diabetic rats. Kinetic analyses revealed that the ranirestat inhibition of AR is uncompetitive and reversible. In the sciatic nerve and lens of STZ-diabetic rats, single oral administration of ranirestat slightly reduced sorbitol levels. However, repeated oral administration of ranirestat for 5, 21, or 60 days enhanced the reducing effect of the ranirestat on sorbitol levels in the sciatic nerves and lens of STZ-diabetic rats with maximum effects after 21 days of treatment. Finally, repeated oral administration of ranirestat for 21 or 42 days dose-dependently improved the STZ-induced decrease in MNCV in STZ-diabetic rats. These findings demonstrate that repeated oral administration of ranirestat reduces sorbitol accumulation and improves MNCV in STZ-diabetic rats, indicating that ranirestat is an agent for the management of diabetic sensorimotor polyneuropathy.

Long-Term Treatment With Ranirestat (AS-3201), a Potent Aldose Reductase Inhibitor, Suppresses Diabetic Neuropathy and Cataract Formation in Rats

We investigated the chronic functional and histopathological changes in the sciatic nerve and lens of streptozotocin (STZ)-diabetic rats and evaluated the preventive effects of ranirestat (AS-3201), a potent aldose reductase inhibitor, on these changes. Sorbitol levels in the sciatic nerve and lens, motor nerve conduction velocity (MNCV), and development of cataracts were measured in STZ-diabetic rats given a ranirestat-admixed diet (0.0005%) for 35 weeks. Ranirestat reduced sorbitol accumulation in the sciatic nerve and improved the decrease in MNCV of STZ-diabetic rats. Morphological and morphometric examination of changes in sural nerve revealed that treatment with ranirestat prevented both the deformity of myelinated fibers and the decrease in their axonal and myelin areas (atrophy). Ranirestat also averted the changes in the size frequency histogram of myelinated fibers. Finally, STZ-diabetic rats developed early lens opacities 8 weeks after STZ injection and had cataract by the end of the experimental period. However, in the ranirestat-treated diabetic rats, no lens opacity was observed in any rat throughout the entire experimental period. This study suggests that the polyol pathway plays an important role in the progress of diabetic neuropathy and cataract formation in STZ-diabetic rats. Ranirestat should be a promising agent for the treatment of complications associated with diabetes, especially neuropathy.

Endoneurial microvascular pathology in feline diabetic neuropathy

Endoneurial capillaries in nerve biopsies from 12 adult diabetic cats with varying degrees of neurological dysfunction were examined for evidence of microvascular pathology and compared to nerves obtained at necropsy from 7 adult non-diabetic cats without clinical evidence of neurological dysfunction. As reported previously [Mizisin, A.P., Nelson, R.W., Sturges, B.K., Vernau, K.M., LeCouteur, R.A., Williams, D.C., Burgers, M.L., Shelton, G.D., 2007. Comparable myelinated nerve pathology in feline and human diabetes mellitus. Acta Neuropathol. 113, 431–442.], the diabetic cats had elevated glycosylated hemoglobin and serum fructosamine levels, decreased motor nerve conduction velocity and compound muscle action potential (CMAP) amplitude, and markedly decreased myelinated nerve fiber densities. Compared to non-diabetic cats, there was a non-significant 26% increase in capillary density and a significant ( P < 0.009) 45% increase in capillary size in diabetic cats. Capillary luminal size was also significantly ( P < 0.001) increased, while an index of vasoconstriction was significantly decreased ( P < 0.001) in diabetic cats compared to non-diabetic controls. No differences in endothelial cell size, endothelial cell number or pericyte size were detected between non-diabetic and diabetic cats. In diabetic cats, basement membrane thickening, seen as a reduplication of the basal lamina, was significantly ( P < 0.0002) increased by 73% compared to non-diabetic controls. Regression analysis of either myelinated nerve fiber density or CMAP amplitude against basement membrane size demonstrated a negative correlation with significant slopes ( P < 0.03 and P < 0.04, respectively). These data demonstrate that myelinated nerve fiber injury in feline diabetic neuropathy is associated with microvascular pathology and that some of these changes parallel those documented in experimental rodent and human diabetic neuropathy.

PROTECTIVE EFFECTS OF BENDAZAC LYSINE ON DIABETIC PERIPHERAL NEUROPATHY IN STREPTOZOTOCIN‐INDUCED DIABETIC RATS

1. Diabetic neuropathy is a many faceted complication of both type I and II diabetes. The aim of the present study was to investigate the effects of bendazac lysine (BDL), an anticataract drug, on experimental diabetic peripheral neuropathy (DPN) in rats. 2. Diabetes was induced in rats by intraperitoneal injection of 75 mg/kg streptozotocin (STZ) dissolved in 0.1 mol/L citrate buffer (pH 4.4). Bendazac lysine was administered to rats at doses of 50, 100 and 200 mg/kg twice a day for 12 weeks. 3. Diabetic rats without treatment showed hypopraxia, polydipsia, polyuria, slow weight gain, cataract, increased tail-flick threshold temperature, decreased motor nerve conduction velocity (nd induced pathological morphological changes of myelinated nerve fibres. All these symptoms were ameliorated in diabetic rats treated with BDL. Bendazac lysine ameliorated the blood glucose concentration, glycosylated haemoglobin levels and insulin levels in the plasma of diabetic rats, reduced aldose reductase activity in erythrocytes and advanced glycation end-products in both nerves and serum and increase the activity of glutathione peroxidase in the nerves and Na(+)/K(+)-ATPase in the nerves and erythrocytes. 4. Bendazac lysine exerts its protective effects against the progression of diabetic peripheral neuropathy in STZ-diabetic rats through multiple mechanisms and is a potential drug for the prevention of deterioration in DPN.

Intraoperative Measurement of Pressure Adjacent to the Ulnar Nerve in Patients with Cubital Tunnel Syndrome

As hand therapists, we commonly treat cubital tunnel syndrome in patients both conservatively and postoperatively. It is interesting to learn that questions still arise regarding the cause of this nerve entrapment. Is it due to compression of the cubital tunnel wall, stretching of the nerve itself, or a combination of these factors? Previous studies have examined interstitial pressure within the cubital tunnel and have shown increased pressure with increased elbow flexion. However, these studies have all been performed in the cadaver lab. In this present study from Japan, pressure around the ulnar nerve was measured during surgery and a link was found to the duration of the disease and the severity of the neuropathy. Method: The study looked at eight patients undergoing decompression of the cubital tunnel. All of the patients complained of pain, numbness and parathesias of the ulnar hand, and loss of strength. The patients also demonstrated a positive Tinel's sign at the elbow, atrophy of the intrinsic muscles, decreased motor nerve conduction velocity, and symptom reproduction with elbow flexion. All eight patients demonstrated severe symptoms of cubital tunnel syndrome warranting surgical decompression. The Akahori classification system was used to grade the severity of the cubital tunnel syndrome. The surgical technique used is described. Pressures in each elbow were recorded at three locations: 1 cm, 2 cm, and 3 cm distal to the proximal edge of the cubital tunnel retinaculum. Measurements at each location were performed with the elbow flexed to 130° and in full extension. The measurements were taken three times and an average of the three was recorded. Statistical Analysis: The Student's t-test was used to evaluate the difference in pressures between elbow flexion and elbow extension and the differences in pressure between elbow flexion and the stages of ulnar nerve palsy. The Pearson's correlation analysis was used to study the relationship between age and pressure, motor nerve conduction velocity and pressure, and disease duration and pressure. Results: The statistical analysis indicates a statistically significant difference in the measurement of extraneural pressure with elbow flexion over elbow extension and increased pressure more proximally to the cubital tunnel than distally. Results of the statistical analysis also show a positive correlation between extraneural pressure with elbow flexion and the severity of the disease at each location in the cubital tunnel. The pressures also correlated positively with motor nerve conduction velocity. Conclusions: Previous studies on pressure around the ulnar nerve in cubital tunnel have been performed in the cadaver lab. This study measures pressure around the ulnar nerve during surgery and finds correlations with the amount of pressure and the severity of the nerve entrapment. A transducer-tipped fiberoptic probe is used to for intraoperative pressure measurement. This device was created for intracranial pressure monitoring. It is simple to use and has a rapid response to pressure changes. Reviewer's Commentary: This study makes no statement regarding the causative factors leading to cubital tunnel syndrome. However, the authors suggest that external compression plays a significant role in the development of ulnar nerve entrapment. They conclude that simple decompression of the ulnar nerve is insufficient and selected anterior transposition of the ulnar nerve as the surgical technique in all eight patients.

Uncoupling Protein 2 Promoter Polymorphism −866G/A Affects Peripheral Nerve Dysfunction in Japanese Type 2 Diabetic Patients

To determine genetic predispositions for diabetic polyneuropathy, we investigated the relationship between the -866G/A polymorphism of uncoupling protein (UCP) 2 and neurological manifestations in 197 type 2 diabetic patients. We first examined whether UCP2 mRNA had been expressed in the dorsal root ganglion (DRG) in four Long-Evans Tokushima Otsuka rats using RT-PCR and electrophoresis. Genotyping of UCP2 promoter polymorphism -866G/A was then performed in 197 unrelated Japanese type 2 diabetic patients, who were subjected to nerve conduction, quantitative vibratory perception, head-up tilt, and heart rate variability tests, by PCR restriction fragment-length polymorphism. The relationships between UCP2 genotype and various nerve functions were analyzed by uni- and multivariable analysis. Expression of UCP2 mRNA was confirmed in rat DRG. Multiple regression analysis clarified the hypothesis that the G/A + A/A genotype was significantly related to decreased motor nerve conduction velocity and impaired blood pressure maintenance on the head-up tilt test. Multiple logistic regression analysis revealed that the G/A + A/A genotypes are a significant risk factor for sensory nerve conduction slowing and orthostatic hypotension. UCP2 promoter gene polymorphism -866 G/A was significantly associated with nerve conduction slowing and vasomotor sympathetic functions. These findings suggest that the higher UCP2 activity related to the A allele has an energy-depleting effect on peripheral nerve function in type 2 diabetic patients.

Ataxia cerebelosa de Norman-Jaeken. Presentación de siete pacientes españoles

To show that the cerebellar ataxias described by Norman and by Jaeken (CDG1a) are the same disease. Seven patients, five females and two males (there were two siblings pairs), who presented a severe cerebellar disease slowly progressive associated with generalized cerebellar atrophy. The sister of one of the patients of the series had been studied because of psychomotor retardation but she died at two years of age due to respiratory problems. An autopsy was carried out that showed severe cerebellar atrophy, and the histological study revealed loss of granular cells and diverse abnormalities of Purkinje's cells, especially focal swellings of 'asteroid bodies' or 'cactus like' type. This suggested to us that Norman's ataxia and CDG1a could be the same pathological entity. All seven patients had severe cerebellar hypoplasia-atrophy and a small brainstem. Most patients showed peripheral neuropathy with decreased motor nerve conduction velocity, but very little decreased sensory nerve conduction velocity. All seven patients had highly raised serum concentrations of asialotransferrin, and heterozygous molecular PMM2 deficit (CDG1a). One of these seven cases was the patient whose sister had histological cerebellar changes corresponding to Norman's ataxia. The findings observed in our series suggest that the diseases described by Norman and Jaeken are the same pathological entity and CDG1a can be the biological basis of the histological changes of the cerebellum in Norman's ataxia. We suggest the name of Norman-Jaeken ataxia or disease for this entity.

SET binding factor 2 (SBF2) mutation causes CMT4B with juvenile onset glaucoma.

The authors report a Japanese family segregating autosomal recessive Charcot-Marie-Tooth disease (CMT) with focally folded myelin, juvenile-onset glaucoma, and a nonsense mutation of SET binding factor 2 (SBF2). The consistent phenotypic features associated with SBF2 mutations are early-onset demyelinating neuropathy, myelin folding, and markedly decreased motor nerve conduction velocities; glaucoma associates with SBF2 nonsense mutations.

Motor nerve conduction analysis of double crush syndrome in a rabbit model

AbstractThe double crush syndrome was proposed by Upton and McComas in 1973, but there are still many unclear points regarding its mechanism. We propose a model that enables electrophysiological study of the same nerve from the same individual over time. We employed 29 rabbits and used their sciatic nerves. (Four rabbits died from infection, and in nine rabbits we could not record the M-wave because the electrodes were off during the course of the study.) Sixteen rabbits were grouped into six experimental groups and one control group. Bipolar stimulus electrodes were buried at three locations in their sciatic nerves. The two areas between the proximal and intermediate electrodes and between the intermediate and distal electrodes were defined as the “nerve proximal part” and “nerve distal part,” respectively. An electrical stimulus was applied via each electrode, and the muscle action potential (M-wave) was recorded from the gastrocnemius. A narrow tube was inserted in the nerve proximal part and a wide tube in the nerve distal part. A decrease in the motor nerve conduction velocity (MCV) was observed in the nerve proximal part (narrow tube) followed by a decrease in MCV in the nerve distal part (wide tube). A wide tube was then inserted in the nerve proximal part and a narrow tube in the nerve distal part. A decrease in MCV was observed in the nerve distal part (narrow tube) followed by a decrease in MCV in the nerve proximal part (wide tube). We believe that these results are important findings in regard to the double crush syndrome (DCS) hypothesis and the reversed DCS hypothesis.

Valeur diagnostique du profil neurophysiologique classique dans les différents phénotypes de la neuropathie héréditaire sensible à la pression

Purpose. – We looked for electrodiagnostic features that raise suspicion of hereditary neuropathy with liability to pressure palsies (HNPP). Method. – A retrospective review of eight cases with confirmed histologic (one case) or chromosome 17 deletion (seven cases) analysis was performed. Results. – Autosomal dominant disease was present in 63% of the patients, 75% being men. Mean age at examination and at first symptom was 27 and 22 years respectively. Five patients have one or more acute nerve palsies, without residual deficit, but one presented sensory symptoms in internal saphena territory. Three patients had others phenotypes: a man presented with four episodes of facial palsy and one woman was asymptomatic; another patient with diabetes mellitus presented an associated chronic sensorimotor polyneuropathy. In agreement with other studies of HNPP we found in most patients a diffuse increase in distal motor latence, contrasting with normal or moderately decreased motor nerve conduction velocity, multiple electrophysiologic entrapment and diffuse reduction in sensory nerve action potential and/or velocity. However, this electrophysiological pattern was incomplete or masked in HNPP with cranial nerves palsies, in asymptomatic form of HNPP or in HNPP associated with polyneuropathy. Conclusion. – These data confirm the clinical phenotypic heterogeneity of the 17p11.2 deletion and highlight the limits of the classic electrophysiological pattern in asymptomatic HNPP or associated with uncommon clinical features.

Neuropathy in diabetic mice overexpressing human aldose reductase and effects of aldose reductase inhibitor.

The present study was designed to examine the effect of aldose reductase (AR) overexpression on the development of diabetic neuropathy by using mice transgenic for human AR. At 8 weeks of age, transgenic mice (Tg) and non-transgenic littermates (Lm) were made diabetic with streptozotocin. After 8 weeks of untreated diabetes, plasma glucose levels and the reduction in body weight were similar between the groups of diabetic animals. Despite the comparable levels of hyperglycaemia, levels of sorbitol and fructose were significantly greater in the peripheral nerve of diabetic Tg than in diabetic Lm (both P < 0.01). Ouabain sensitive Na(+),K(+)-ATPase activity was similarly decreased in both diabetic Tg and Lm. Protein kinase C activity in the sciatic nerve membrane fraction was unaffected by diabetes in Lm, but was reduced by nearly 40% in the diabetic Tg. Although both groups of diabetic animals exhibited a significant decrease in tibial nerve motor nerve conduction velocity (MNCV), this decrease was significantly more severe (P < 0.01) in diabetic Tg than in diabetic Lm. Consistent with these findings, nerve fibre atrophy was significantly more severe in diabetic Tg than in diabetic Lm (P < 0.01). These findings implicate increased polyol pathway activity in the pathogenesis of diabetic neuropathy. In support of this hypothesis, treating diabetic Tg with an aldose reductase inhibitor (WAY121-509, 4 mg/kg/day) for 8 weeks significantly prevented the accumulation of sorbitol, the decrease in MNCV and the increased myelinated fibre atrophy in diabetic Tg.

Axonal Charcot-Marie-Tooth Disease and the Neurofilament Light Gene ( NF-L)

Axonal Charcot-Marie-Tooth Disease and the Neurofilament Light Gene ( NF-L)

Guidelines for diagnosis of hereditary neuropathy with liability to pressure palsies.

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant peripheral neuropathy [1]. HNPP patients present with variously located recurrent peripheral nerve palsies, or sensory loss, often precipitated by minor trauma or compression. The dysfunction is painless, distinguishing HNPP from another inherited recurrent focal neuropathy, namely hereditary neuralgic amyotrophy [2,3]. Usually the onset is acute, but progressive weakness may occur. In most cases, patients recover within days or weeks, but relapses are frequent, and paresis may last for long periods. A number of patients show signs of a symmetrical distal neuropathy without acute nerve palsies [3,4]. Neurological examination reveals weakness and sensory loss in the distribution of affected nerves; tendon re exes are often depressed or abolished, pes cavus is infrequent, scoliosis is rare, and there is no nerve hypertrophy or CNS involvement [1]. HNPP is probably underdiagnosed because of its usually benign course. In addition, about 10±15% of mutation carriers remain clinically asymptomatic, suggesting incomplete penetrance [4,5]. Given the poverty of the clinical ®ndings in HNPP, electrophysiological examination is of great importance for its diagnosis. Nerve conduction studies reveal a characteristic pattern of mildly decreased motor nerve conduction velocities (MNCV), prolonged distal motor latencies (DML) predominantly at nerve entrapment sites, and altered sensory nerve action potentials, even in clinically nonaffected nerves or in asymptomatic at-risk individuals [6]. A simple standardized electrophysiological examination is suf®cient to identify adult gene carriers: bilaterally delayed median DML and reduced sensory velocity in the palmwrist segment, and a delayed DML or reduced MNCV in the peroneal nerve, are highly suggestive of the disease when there is a family history of HNPP [4]. Peripheral nerve biopsies show a characteristic focal sausage-shaped thickening of the myelin sheath in about 25% or less of the internodes [7], which were designated by Madrid and Bradley as `tomacula' [8,9]. The tomaculous changes are not speci®c to HNPP and can occur, even in a higher frequency in Charcot±Marie±Tooth disease or Dejerine±Sottas phenotype [10]. Some patients do not show these speci®c changes, but rather non-speci®c ®ndings with either extensive loss of ®bers, or excessive variability in thickness and length of myelin internodes [1]. However, molecular analysis has not yet been performed in these HNPP patients. An interstitial deletion in the 17p11.2 region is associated with the disorder in most HNPP families [11±16]. This is the same region, designated CMT1A monomer unit, which contains the gene encoding the peripheral myelin protein 22 (PMP22), which is duplicated in the more frequently diagnosed neuropathy, Charcot±Marie±Tooth disease type 1A (CMT1A) [11±16]. Thus, it was hypothesized that unequal crossing-over between chromosome 17 homologues would generate a duplication that could lead to CMT1A, or a deletion that could result in HNPP. This hypothesis was reinforced by the existence of de novo deletions in HNPP patients without affected parents, most of them with a paternal origin [11,13,15], but sometimes with a maternal origin [17±20]. Investigators have postulated a gene dosage effect of PMP22 contained in the CMT1A monomer unit. This hypothesis has been con®rmed by the demonstration that PMP22 protein level expression in myelin correlates with the number of gene copies [21,22]. Moreover, it has recently been shown that PMP22 mRNA level is lower in the sural nerve of HNPP patients compared with normal controls, and correlates with disease severity [23,24]. The causative role of the PMP22 gene has been de®nitely proven by the existence, in rare HNPP patients, of mutations in this gene, probably causing a loss of function Neuromuscular Disorders 10 (2000) 206±208

Effect of inhalation exposure to 2-bromopropane on the nervous system in rats

Exposure to 2-bromopropane (2-BP) is suspected to have adverse effects on the nervous system. The aim of this study was to investigate whether the exposure of rats to 2-BP had neurotoxic effects using histological and electrophysiological studies. Wistar strain male rats were exposed daily to either 100 or 1000 ppm 2-BP or to fresh air for 8 h a day for 12 weeks. Body weight was measured before exposure and every 2 weeks. Motor nerve conduction velocity (MCV) and distal latency (DL) were measured before exposure and every 4 weeks during exposure. Histological examination of the nervous system was also performed. Exposure of rats ( n=9) to 1000 ppm resulted in suppression of body weight gain and a significant decrease in brain weight compared to the control ( n=9). Electrophysiological measurements showed a significant decrease in MCV in 1000 ppm exposed rats at 8 weeks and significant prolongation of DL at 8 and 12 weeks. Abnormalities of the myelin sheath were detected in the common peroneal nerves. In 100-ppm exposed rats ( n=9), no significant changes were noted in body weight and the peripheral nerve. In conclusions, long-term exposure to 1000 ppm of 2-BP may result in peripheral neuropathy in rats.

Ultrasound therapy effect in carpal tunnel syndrome

Objective: To investigate the overall effect of repeated ultrasound treatment in carpal tunnel syndrome (CTS). Design: Patient-blinded, placebo-controlled, before-after treatment trial. Setting: University hospital PM&R department outpatient clinic and neurology department electromyography laboratory. Patients: Eighteen women with diagnosis of CTS in 30 hands. Interventions: Three groups, each with 10 cases of CTS, were randomly established. Continuous ultrasound therapy, with intensities of 1.5W/cm 2 (group A), 0.8W/cm 2 (group B), and 0.0W/cm 2 (group C), was applied to palmar carpal tunnel area for 5 minutes, 5 days a week, for 2 weeks. Outcome Measures: Patients were evaluated clinically and electrophysiologically before and after the treatment. Results: At the end of treatment, statistically significant improvement was obtained in clinical parameters in all groups: pain ( p < .05), pain/paresthesia at night/day ( p < .05), and frequency of awakening at night ( p < .05). Although there was no statistically significant before-after difference in electrophysiologic studies, slightly decreased motor nerve conduction velocity and increased motor distal latency were noted in groups A and B, but not in group C. Conclusion: Ultrasound therapy in CTS was comparable to placebo ultrasound in providing symptomatic relief, and the probability of a negative effect on motor nerve conduction needs to be considered.

Increased resitance to hypoxic conduction block in sciatic nerves of diabetic rats: Effects of extracellular glucose concentration and of aldose reductase inhibition

This study examined the effect of the aldose reductase inhibitor (ARI), ponalrestat, on decreased motor nerve conduction velocity (MNCV) and increased resistance to hypoxic conduction block (RHCB) in diabetic rats. The effects of 5 mmol/L, and 25 mmol/L glucose on RHCB were also determined. Twenty streptozotocin-diabetic rats formed two groups; untreated and ponalrestat-treated (300 mg/kg diet/day); 10 non-diabetic rats acted as controls. MNCV was measured in vivo after 4 weeks of diabetes ± treatment in the sciatic/tibialis system and rats were killed 48–72 h later. The median nerves were removed and assayed for polyol pathway metabolites by gas chromatography. The sciatic nerves were dissected to form endoneurial preparations for the recording of compound action potentials (CAPs) in vitro and maintained in media with either 5 (standard) or 25 (high) mmol/L glucose and initially gassed with 95% O 2 5% CO 2 . Oxygen content was then reduced to 8% for 40 min to study the effect of this period of hypoxia on CAP amplitude. MNCV (m/s ± SD) in diabetic rats (43.86 ± 4.86) was decreased compared to controls (52.24 ± 6.59) and this decrease was absent in the ARI-treated group (52.24 ± 6.90). The decline in CAP amplitude during a 40-min hypoxic period was greater in controls than in diabetics. Ponalrestat treatment caused a decline which was mid-way between these two in standard medium and closer to that seen in control preparations in high glucose medium. These findings give further support to the involvement of the sorbitol pathway in the development of the acute MNCV deficit in diabetic rats and indicate that it may have a partial role in the development of increased resistance to hypoxic conduction block in peripheral nerves.

Characterization of a Novel Aldose Reductase Inhibitor, TAT, and Its Effects on Streptozotocin-Induced Diabetic Neuropathy in Rats

TAT ([5-(3-thienyl)tetrazol-1-yl]acetic acid) is a novel aldose reductase (AR) inhibitor. It exhibited highly potent inhibition of partially purified AR from rat lens (IC50 = 2.1 x 10(-8) M), rabbit lens (IC50 = 2.3 x 10(-8) M) and human placenta (IC50 = 2.8 x 10(-8) M). On the other hand, TAT had a weak inhibitory activity against mouse liver aldehyde reductase (ALR) (IC50 = 2.4 x 10(-6) M) and poor inhibitory activity against several adenine nucleotide-requiring enzymes. Against rat lens AR, TAT exhibited an uncompetitive inhibition at a concentration of 1.0 x 10(-8) M and a mixed type inhibition at higher concentrations. TAT inhibited sorbitol accumulation in the isolated rat sciatic nerve (IC50 = 1.0 x 10(-6) M), rat lens (IC50 = 5.7 x 10(-6) M), human erythrocytes (IC50 = 2.5 x 10(-7) M), and rabbit erythrocytes (IC50 = 2.1 x 10(-7) M) incubated with high glucose concentrations. The oral administration of TAT (5-100 mg/kg/day) to streptozotocin (STZ)-induced diabetic rats during a 5-day treatment period decreased the sorbitol content in the sciatic nerve, dose-dependently (ED50: 8.8 mg/kg/day for the prevention and 9.0 mg/kg/day for the reversal). Moreover, TAT (2.5-40 mg/kg/day) improved the decreased motor nerve conduction velocity (MNCV) after a 14-day treatment period. There was a significant correlation between MNCV and sciatic nerve sorbitol content. From these results, TAT is expected to be useful for the clinical treatment of diabetic complications.

Effects of novel aldose reductase inhibitors, M16209 and M16287, on streptozotocin-induced diabetic neuropathy in rats

We investigated the effects of novel aldose reductase inhibitors, M16209 (1-(3-bromobenzo[b]furan-2-ylsulfonyl)hydantoin) and M16287 (1-(3-chlorobenzo[b]furan-2-ylsulfonyl)hydantoin), on neuropathy in streptozotocin-induced (STZ) diabetic rats. Both compounds (3–100 mg/kg per day, p.o.) dose dependently improved the decreased motor nerve conduction velocity in the sciatic nerve during a 14-day treatment period. These compounds also partially ameliorated the diabetes-induced histological changes in the sciatic nerve. A distinct increase in sorbitol content and a slight decrease in myo-inositol content was observed in the sciatic nerve of STZ diabetic rats, and the sorbitol accumulation was dose dependently suppressed by treatment with M16209 and M16287. Treatment started at an earlier period was more effective in the suppression of sorbitol accumulation. There was a significant correlation between motor nerve conduction velocity and nerve sorbitol content, whereas there was none between motor nerve conduction velocity and myo-inositol content. The present study indicates that M16209 and M16287 are potent aldose reductase inhibitors expected to be useful for the treatment of diabetic complications.