Neuropathy In Man Research Articles

The effect of 12 weeks aerobic, resistance and combined trainings on peripheral vascular disease in type 2 diabetes with peripheral neuropathy in men

Type 2 diabetes is caused by more complications. One complication that occurs in some cases is peripheral vascular disease. Early diagnosis is very important to assess peripheral vascular disease. 44 men with type 2 diabetes were randomly divided into four groups of aerobic, resistance, combined and control. Intensity of aerobic exercise was 70–75 percent of maximum heart rate for 25–45 min, Resistance training consists of two to three sets with 8–12 repetitions and combined training consists of both aerobic and resistance training, three times a week for 12 weeks. Ankle brachial index (ABI) measurements and blood samples were analyzed before and after intervention. The collected data were analyzed using ANOVA. The resistance and combined training groups showed a significant increase in the left ABI compared to pretest (P < 0.05) Also, the aerobic and resistance training groups showed a significant increase in the right ABI compared to pretest (P < 0.05). The resistance training group was more effective than aerobic and combined training program in reduction the peripheral vascular disease.

Nanoparticles and neuropathy in man and animals-A review

Nanoparticles and neuropathy in man and animals-A review

Small-fibre neuropathy in men with type 1 diabetes and erectile dysfunction: a cross-sectional study

Aims/hypothesisThe aim of this study was to identify the contribution of small- and large-fibre neuropathy to erectile dysfunction in men with type 1 diabetes mellitus.MethodsA total of 70 participants (29 without and 41 with erectile dysfunction) with type 1 diabetes and 34 age-matched control participants underwent a comprehensive assessment of large- and small-fibre neuropathy.ResultsThe prevalence of erectile dysfunction in participants with type 1 diabetes was 58.6%. After adjusting for age, participants with type 1 diabetes and erectile dysfunction had a significantly higher score on the Neuropathy Symptom Profile (mean ± SEM 5.3 ± 0.9 vs 1.8 ± 1.2, p = 0.03), a higher vibration perception threshold (18.3 ± 1.9 vs 10.7 ± 2.4 V, p = 0.02), and a lower sural nerve amplitude (5.0 ± 1.1 vs 11.7 ± 1.5 mV, p = 0.002), peroneal nerve amplitude (2.1 ± 0.4 vs 4.7 ± 0.5 mV, p < 0.001) and peroneal nerve conduction velocity (34.8 ± 1.5 vs 41.9 ± 2.0 m/s, p = 0.01) compared with those without erectile dysfunction. There was also evidence of a marked small-fibre neuropathy with an impaired cold threshold (19.7 ± 1.4°C vs 27.3 ± 1.8°C, p = 0.003), warm threshold (42.9 ± 0.8°C vs 39.0 ± 0.9°C, p = 0.005) and heart rate variability (21.5 ± 3.1 vs 30.0 ± 3.7 beats/min, p = 0.001) and reduced intraepidermal nerve fibre density (2.8 ± 0.7 vs 5.9 ± 0.7/mm, p = 0.008), corneal nerve fibre density (12.6 ± 1.5 vs 23.9 ± 2.0/mm2, p < 0.001), corneal nerve branch density (12.7 ± 2.5 vs 31.6 ± 3.3/mm2, p < 0.001) and corneal nerve fibre length (8.3 ± 0.7 vs 14.5 ± 1.0 mm/mm2, p < 0.001) in participants with type 1 diabetes and erectile dysfunction. Erectile dysfunction correlated significantly with measures of both large- and small-fibre neuropathy.Conclusions/interpretationSmall-fibre neuropathy is prominent in patients with type 1 diabetes, and is associated with erectile dysfunction and can be objectively quantified using corneal confocal microscopy. This may allow the identification of patients who are less likely to respond to conventional therapies such as phosphodiesterase type 5 inhibitors.

Testosterone Concentrations and Cardiovascular Autonomic Neuropathy in Men with Type 1 Diabetes in the Epidemiology of Diabetes Interventions and Complications Study (EDIC).

Previous studies have reported that lower testosterone concentrations are associated with cardiovascular autonomic neuropathy (CAN), a risk factor for cardiovascular events. However, no studies have examined this relationship in men with type 1 diabetes, who are at high risk for CAN. The aim of this study was to examine the associations between testosterone concentrations and measures of CAN in a large, well-characterized cohort of men with type 1 diabetes. We conducted an analysis of men in the Diabetes Control and Complications Trial (DCCT), a randomized trial of intensive glucose control, and its observational follow-up the Epidemiology of Diabetes Intervention and Complications (EDIC) Study. Testosterone was measured by liquid chromatography mass spectrometry in stored samples from EDIC follow-up years 10 and 17. Regression models were used to assess the cross-sectional relationships between testosterone and CAN measures. The main CAN measure from EDIC follow-up year 17 was a standardized composite of R-R variation with paced breathing < 15, or R-R variation 15-20 combined with either a Valsalva ratio ≤ 1.5 or a decrease in diastolic blood pressure > 10 mm Hg upon standing. Continuous R-R variation and Valsalva ratio were secondary outcomes. Lower total and bioavailable testosterone concentrations at follow-up years 10 and 17 were not associated with the presence of CAN at year 17. In analyses using Valsalva ratio as a continuous measure, higher total (P = 0.01) and bioavailable testosterone concentrations (P = 0.005) were associated with a higher (more favorable) Valsalva ratio after adjustment for covariates including age, body mass index, smoking status, hypertension, and glycemia. Testosterone levels are not associated with CAN among men with type 1 diabetes. Although testosterone is associated with a higher Valsalva ratio, a more favorable indicator, the clinical significance of this association is not known.

VEGF levels in diagnosis of vasculitic neuropathy.

Vascular endothelial growth factor (VEGF) is secreted from endothelial cells and pericytes in response to hypoxia. It induces angiogenesis and microvascular hyperpermeability. We observe serum VEGF concentrations in some patients with vasculitic neuropathy. Plasma VEGF was measured using GenWay's human VEGF ELISA Kit, which is based on standard sandwich enzyme-linked immune-sorbent assay technology. Human VEGF specific-specific monoclonal antibodies are precoated onto 96-well plates. The human specific detection polyclonal antibodies are biotinylated. The test samples and biotinylated detection antibodies were added to the wells subsequently and then followed by washing with PBS or TBS buffer. Avidin-Biotin-Peroxidase Complex was added and unbound conjugates were washed away with PBS or TBS buffer. HRP substrate TMB was used to visualize HRP enzymatic reaction. The VEGF levels were measured in 5 patients with vasculitic neuropathy and 8 healthy controls. Plasma VEGF was higher in subjects with vasculitic neuropathy as compared to controls. In the control group, we obtained VEGF levels from 9.8 pg/mL up to 15 pg/mL with an average of 11.6 pg/mL for males and 8.9 pg/mL up to 14.5 pg/mL with average of 11.2 pg/mL for females. In female patients with vasculitic neuropathy the plasma VEGF levels were between 79.9 pg/mL and 111.2 pg/mL, with an average of 92.375 pg/mL. We had one case with vasculitic neuropathy in men, in which the plasma VEGF level was 102.9 pg/mL. The results from our study indicate that plasma VEGF levels are significantly associated with vasculitic neuropathy and may be used to predict this disease.

Gender differences in diabetes-related lower extremity amputations.

Diabetes is a major cause of morbidity and mortality in the United States, with much of the economic and social costs related to macrovascular and microvascular complications, such as myocardial infarctions, renal failure, and lower extremity amputations. While racial/ethnic differences in diabetes are well documented, less attention has been given to differences in diabetes outcomes by gender. Does gender influence the rate of diabetes-related lower extremity amputations and/or the rate of mortality after amputation? I reviewed the literature utilizing peer-reviewed publications found through MEDLINE searches. WHERE ARE WE NOW?: Major complex gender differences exist in diabetes-related lower extremity amputations: men are more likely to undergo lower extremity amputations, but women apparently have higher mortality related to these procedures. The reasons for such differences are not entirely clear, but it appears biologic factors may play important roles (increased rates of peripheral vascular disease and peripheral neuropathy in men, interaction between gender and cardiac mortality in women). WHERE DO WE NEED TO GO?: More research is warranted to confirm gender differences in diabetes-related lower extremity amputation mortality and explore underlying mechanisms for the gender differences in lower extremity amputations and its associated mortality. HOW DO WE GET THERE?: Exploring gender disparities in diabetes-related outcomes, such as lower extremity amputations, will need to become a national priority from a research (eg, National Institutes of Health) and policy (eg, Centers for Medicare and Medicaid Services) perspective. Only when we have a better understanding of the causes of such differences can we begin to make strides in addressing them.

Earlier development of diabetic neuropathy in men than in women with type 2 diabetes mellitus

Data about the prevalence of diabetic neuropathy (DN) differ substantially, depending on the population and diagnostic methods. Sex-specific differences in DN are rarely discussed. The aims of the present study were to assess the prevalence of, and analyze sex differences in, DN in a hospital population with type 2 diabetes mellitus (T2DM) over a period of 18 years. In this retrospective study performed at a university hospital endocrinology clinic in Sofia, patient clinical records from 1990-2007 were examined. Patients were included in the database only at their first admission. Data from 1705 patients with T2DM were analyzed (961 women, 744 men; mean [SD] age, 60.0 [11.9] years; diabetes duration, 9.9 [8.4] years; glycosylated hemoglobin, 9.0% [2.2%]; and body mass index, 29.4 [6.0] kg/m²). Obesity (46.3% vs 32.0%; P < 0.001), hypertension (86.7% vs 77.8%; P < 0.001), and dyslipidemia (61.2% vs 55.0%; P < 0.05) were significantly more common in women than in men, respectively. The prevalence of DN was 78.8%, with no significant sex differences. However, prevalence differed with time, corresponding to the frequency of application of electrophysiologic (electromyograms) or semiquantitative instrumental diagnostic methods. In men, the median (25th-75th percentiles) interval between diagnosis of T2DM and diagnosis of DN was 6 (1-12) years; in women, the interval was 8 (4-13) years (P < 0.01). In this study of Bulgarian patients with T2DM, women were at higher macrovascular risk than were men. A high prevalence of DN was observed among these patients. The period from the diagnosis of T2DM to DN was shorter in men than in women-this necessitates earlier screening and therapeutic intervention for DN in men. Reasons for this sex difference may include differences in lifestyle and the testosterone deficiency that is common in men with diabetes, leading to a more pronounced deficit of neurosteroids.

Expression changes of apoptotic-related proteins in nerve tissues of rats treated with allyl chloride

Allyl chloride (AC) is widely used in industries as raw material and has been reported to produce occupational peripheral neuropathies in man chronically exposure to it. Although many studies have been done addressing to it, the mechanisms still remain unclear. To elucidate the molecular mechanism of neuropathy induced by AC, we measured the contents of glutathione (GSH), Bcl-2, Bax, cytochrome c (CytC) and Caspase-3 in a time-dependent manner by biochemical and quantitative immunoblotting techniques in rats’ cerebrum and spinal cord after 3, 6, 9 and 12 weeks of AC intoxication. The results showed that the levels of Bcl-2 of cerebrum and spinal cord significantly ( P < 0.05) decreased after 9 and 6 weeks of AC intoxication, respectively, while GSH levels decreased after 12 week. However, the levels of Bax, CytC and Caspase-3 significantly ( P < 0.05) increased both in cerebrum and spinal cord. Bax levels of cerebrum and spinal cord increased after 12 and 9 weeks of AC administration, respectively. The levels of CytC and Caspase-3 also went up after 9 weeks of AC treatment in cerebrum and 9, 6 weeks in spinal cord, respectively. Thus, subchronic exposure to AC affected the expressions of apoptotic-related proteins in the central nervous system (CNS) and peripheral nervous system (PNS) tissues and the time dependent changes of these indexes occurred. The regulatory mechanism of apoptosis might be involved and served as one of mechanisms of toxic neuropathy induced by AC.

REPLY FROM DRS. BRASSARD AND POIRIER

To the Editor : We would like to thank Dr. Broderick ([2a][1]) for his interest and thoughtful comments regarding our manuscript. We agree that sympathetic dominance should not be ruled out for the increased (or preserved) exercise capacity observed in our subjects with high peak systolic blood

697: Nonarteritic Anterior Ischemic Optic Neuropathy in Men Using Sildenafil Citrate for Erectile Dysfunction: A Review of > 44,800 Patients in Clinical and Observational Studies

697: Nonarteritic Anterior Ischemic Optic Neuropathy in Men Using Sildenafil Citrate for Erectile Dysfunction: A Review of > 44,800 Patients in Clinical and Observational Studies

Optic nerve and neuroprotection strategies

Experimental studies have yielded a wealth of information related to the mechanism of ganglion cell death following injury either to the myelinated ganglion cell axon or to the ganglion cell body. However, no suitable animal models exist where injury can be directed to the optic nerve head region, particularly the unmyelinated ganglion cell axons. The process of relating the data from the various animal models to many different types of optic neuropathies in man must, therefore, be cautious. Extensive studies on the isolated optic nerve have yielded valuable information on the way white matter is affected by ischaemia and how certain types of compounds can attenuate the process. Moreover, there are now persuasive data on how ganglion cell survival is affected when the ocular blood flow is reduced in various animal models. As a consequence, the molecular mechanisms involved in ganglion cell death are fairly well understood and various pharmacological agents have been shown to blunt the process when delivered before or shortly after the insult. A battery of agents now exist that can blunt animal ganglion cell death irrespective of whether the insult was to the ganglion cell body or the myelinated axon. Whether this information can be applied for use in patients remains a matter of debate, and major obstacles need to be overcome before the laboratory studies may be applied clinically. These include the delivery of the pharmacological agents to the site of ganglion cell injury and side effects to the patients. Moreover, it is necessary to establish whether effective neuroprotection is only possible when the drug is administered at a defined time after injury to the ganglion cells. This information is essential in order to pursue the idea that a neuroprotective strategy can be applied to a disease like glaucoma, where ganglion cell death appears to occur at different times during the lifetime of the patient.

Endoneurial capillary abnormalities presage deterioration of glucose tolerance and accompany peripheral neuropathy in man.

To explore whether microangiopathy is associated with disturbed glucose tolerance and peripheral neuropathy, we assessed endoneurial capillary morphology in sural nerve biopsies from men with diabetes, impaired glucose tolerance (IGT), and normal glucose tolerance (NGT). Baseline morphology was related to glucose tolerance and neuropathy at baseline and at follow-up 6 years later. Capillary density (in number per millimeters squared) at baseline was higher in subjects with diabetes (n = 10) compared with those with NGT (n = 5) at follow-up (median [interquartile range]) (86.0 [24.3] vs. 54.9 [17.1]; P = 0.0200) and in those progressing from IGT to diabetes (n = 4) compared with those with persistent IGT (n = 4) (86.7 [25.2] vs. 54.1 [14.6]; P = 0.0433). The capillary luminal area (in micrometers squared) was lower in subjects with NGT progressing to IGT (n = 2) or subjects with IGT progressing to diabetes (n = 3) compared with subjects with constant NGT (n = 6) or constant IGT (n = 4) (11.9 [2.4] vs. 20.8 [7.8]; P = 0.0201). The capillary basement membrane area (in micrometers squared) was increased in patients with peripheral neuropathy (n = 10) compared with those without (n = 7) (114.6 [68.8] vs. 75.3 [28.7]; P = 0.0084). In conclusion, increased capillary density was associated with current or future diabetes, decreased capillary luminal area with future deterioration in glucose tolerance, and increased basement membrane area with peripheral neuropathy.

Preclinical diabetic cardiomyopathy: relation of left ventricular diastolic dysfunction to cardiac autonomic neuropathy in men with uncomplicated well-controlled type 2 diabetes

Diabetic cardiomyopathy is an ill-defined entity. This study was designed to explore the possible association between left ventricular diastolic dysfunction (LVDD) and cardiac autonomic neuropathy (CAN) independently from metabolic control. Three groups of 10 age-matched men each with well-controlled type 2 diabetes were studied: (1) subjects with normal diastolic function, (2) subjects with LVDD characterized by impaired LV relaxation, and (3) subjects with a more severe form of LVDD characterized by a pseudonormalized pattern of LV filling. No subject had evidence of clinical diabetic complications, coronary artery disease (CAD), hypertension, congestive heart failure, or thyroid or overt renal disease, and all had a negative maximal exercise test. LVDD was evaluated by Doppler echocardiographic and CAN was evaluated using spectral analysis of heart rate variability (HRV; time and frequency domains) from 24-hour Holter recordings. Findings showed that the high frequency power (HF: 0.15 to 0.4 Hz) tends to decrease with worsening diastolic function; 5.0 ± 0.2 ms 2 (mean ± SE) in group 1, 4.2 ± 0.3 ms 2 in group 2, and 3.9 ± 0.4 ms 2 ( P = .03) in group 3, respectively, whereas the low frequency power (LF: 0.04 to 0.15 Hz) was similar between groups. In the time domain, the mean squared differences of the successive RR intervals (rMSDD) also showed the same pattern, ie, 31.0 ± 2.8 ms, 23.8 ± 1.6 ms, and 21.5 ± 2.9 ms in groups 1, 2, and 3, respectively ( P = .03). The E/A ratio correlated significantly with indices of parasympathetic modulation (HF; r = 0.448, P = .013; rMSDD: r = 0.457, P = .011; pNN50: r = 0.425, P = .019). LVDD and CAN are associated in patients with otherwise uncomplicated well-controlled type 2 diabetes. The parameters defining these 2 abnormalities may serve to better define diabetic cardiomyopathy as a distinct entity and could eventually become useful prognostic indicators as it has been shown in nondiabetic populations.

Erectile and endothelial dysfunction in Type II diabetes: a possible link.

The aim of this study was to evaluate the relation between erectile dysfunction and endothelial functions, coagulation activation, peripheral and autonomic neuropathy in men with Type II (non-insulin-dependent) diabetes mellitus. We studied 30 Type II diabetic patients with symptomatic erectile dysfunction and 30 potent diabetic patients matched for age and disease. Endothelial functions were assessed with the L-arginine test, plasma thrombomodulin and cell adhesion molecules circulating concentrations. Haemostasis was evaluated with markers of thrombin activation and fibrinolysis. Quantitative sensory testing (vibratory, warming, and heat-pain thresholds), cardiovascular reflex tests and 24-h blood pressure monitoring were used to assess peripheral or autonomic neuropathy. Mean erectile score and HbA1c were 10.5+/-5.8 and 8.3+/-1.6% in patients with erectile dysfunction, and 24.0+/-0.7 and 6.8+/-1.4% in those without erectile dysfunction, respectively (p < 0.001); there was a significant relation between HbA1c and erectile function score in patients with erectile dysfunction (r = -0.45, p = 0.02). The decrease in blood pressure and platelet aggregation in response to L-arginine was lower (p < 0.05-0.02) in patients with erectile dysfunction, whereas soluble thrombomodulin, P-selectin and intercellular cell ahhesion molecule-1 concentrations were higher (p < 0.05-0.02). Indices of coagulation activation (F1 + 2 and D-dimers) and reduced fibrinolysis (PAI-1) were also found to be higher in erectile dysfunction patients. Heat-pain and warm perception thresholds. as well as cardiovascular reflex tests, were most commonly abnormal in patients with erectile dysfunction (p < 0.05). In multivariate analysis, HbA1c, MBP response to L-arginine, P-selectin, indices of coagulation, and quantitative sensory testing were independent predictors of erectile function score. Erectile dysfunction in diabetic men correlates with endothelial dysfunction. A reduced nitric oxide activity might provide a unifying explanation.

The history of folic acid.

The history of folic acid.

Sorbitol and myo-inositol levels and morphology of sural nerve in relation to peripheral nerve function and clinical neuropathy in men with diabetic, impaired, and normal glucose tolerance.

Sorbitol and myo-inositol levels and morphology of sural nerve were compared with nerve function and clinical neuropathy in men with diabetic, impaired (IGT), and normal glucose tolerance. After neurography of sural nerve and determinations of sensory thresholds for vibration, warm and cold on the foot, whole nerve sural nerve biopsy was performed in 10 men with Type 1 diabetes mellitus, 10 with IGT, and 10 with normal glucose tolerance. Polyol levels were assessed by gas-liquid chromatography/mass spectrometry. Sural nerve amplitudes were significantly lower and sorbitol levels significantly higher in diabetic patients (median (interquartile range)) (3.7 (3.5) microV and 643 (412) pmol/mg protein, respectively) both compared with IGT (11.3 (10.6)microV; P = 0.04 and 286 (83) pmol/mg protein; P = 0.0032, respectively) and normally glucose tolerant (10.0 (11.6); P = 0.0142 and 296 (250) pmol/mg protein; P = 0.0191, respectively) subjects. There were no differences in nerve morphology between the three groups. Nerve myo-inositol levels correlated, however, positively with cluster density (rs = 0.56; P = 0.0054). In diabetic and IGT subjects, sural nerve amplitudes (2.6 (3.8) vs. 12.1 (10.6) microV; P = 0.0246) and myelinated nerve fibre density (MNFD; 4,076 (1091) vs. 5,219 (668) nerve fibres/mm2; P = 0.0021) were significantly lower in nine subjects with clinical neuropathy than in 10 without. Nerve degeneration (i.e. MNFD) correlated with clinical neuropathy but not with glucose tolerance status whereas nerve myo-inositol levels positively correlated with signs of nerve regeneration (i.e. increased cluster density).

Neural architecture in transected rabbit sciatic nerve after prolonged nonreinnervation.

Observations have been made on the rabbit sciatic nerve distal to a transection, with survival periods of up to 26 mo and prevention of reinnervation. It was confirmed that the nerve becomes compartmented by fibroblast processes and that a zone of fine collagen fibrils develops around the Schwann cell columns that constitute the Büngner bands. The Schwann cells become progressively more atrophic but after 6 mo of denervation still expressed low affinity p75 nerve growth factor receptor (NGFR), the latest stage at which this was examined. NGFR was also expressed by the processes of the fibroblasts producing the endoneurial compartmentation. By 26 mo after transection the site of previous nerve fibres was indicated by sharply demarcated domains of approximately circular outline in transverse section consisting of densely packed longitudinally oriented collagen fibrils. Some of these domains still possessed centrally situated Schwann cells or residual basal lamina but many were acellular. The central collagen fibrils in these domains were of smaller diameter than those situated peripherally but were of larger size than those that form around the Büngner bands during wallerian degeneration. The peripherally located fibrils in the domains were of the same calibre as for normal endoneurial collagen. The collagen domains were encircled by fibroblast processes or at times enclosed in a perineurial cell ensheathment. Long-standing axonal loss therefore leads to a striking reorganisation of the internal architecture of peripheral nerve trunks. The findings may be relevant for the interpretation of the appearances in chronic peripheral neuropathies in man.

THE ANATOMY OF ULNAR NEUROPATHY AT THE ELBOW

S164 Introduction: There is an increased frequency of perioperative ulnar neuropathy in men compared to women. [1-3] Most authors have suggested an anatomical cause for ulnar neuropathy; however, none have described anatomical differences between genders. Therefore, we undertook the following studies to evaluate anatomical differences at the elbow between genders. Methods: First, detailed and careful dissection was performed on male and female embalmed and unembalmed cadavers to determine the course and anatomical relationships of the ulnar nerve at the elbow. Second, ultrasound measurements of the elbow region were made to quantify the amount of fat surrounding the ulnar nerve at the cubital tunnel and at the point where the nerve passes on the medial aspect of the coronoid process. Three male and three female volunteers who were similar in age and body fat % were matched for comparison. Finally, the osteology of the proximal ulna was evaluated in 29 male and 14 female skeletons. Specific measurements were made of the tubercle on the coronoid process. Results: No gross anatomical differences were found between genders regarding the course of the ulnar nerve through the upper limb. However, there was a strikingly larger (2-to-19 times greater) fat content on the medial aspect of the elbow in women compared to men, and the tubercle of the coronoid process was approximately 1.5 times larger in men (P <or=to .002, rank sum test). Discussion: The tubercle of the coronoid process (Figure 1) is a likely area for external compression-induced ischemia of the ulnar nerve because the nerve and its arterial supply (the posterior ulnar recurrent artery) are covered at the tubercle only by skin, subcutaneous fat, and a very thin aponeurosis of the flexor carpi ulnaris. Importantly, this tubercle is larger, and the nerve and blood vessels passing by it are less protected by subcutaneous fat, in men than in women. Our findings suggest that these two anatomical differences between men and women may contribute to the increased frequency of perioperative ulnar neuropathy in men.Figure 1: The ulnar nerve and its primary blood supply in the proximal forearm, the posterior ulnar recurrent artery, are very superficial and appear to be susceptible to compression from external pressure as they pass posteriomedially to the tubercle of the caronoid process.

Redistribution of axoplasm in the motor root in experimental diabetes.

Early experimental diabetes is associated with a reduction in axonal caliber. To elucidate the changes of nerve caliber further, we investigated the proximal and distal regions of the anterior root of rats after 5 weeks of streptozocin-induced diabetes. After vascular perfusion fixation, the fifth lumbar motor root was excised and two 3-mm segments were isolated, one at the level of the spinal cord and one at the dorsal root ganglion. The areas of myelinated fibers and their axons were measured by point counting. Axons from diabetic mice were enlarged proximally as compared to the controls, and reduced distally. It has been hypothesized that the reduction in axonal caliber is caused by an impairment of axonal transport of structural proteins rather than by osmotic shrinkage. Our findings indicate a redistribution of axoplasm in the nerves of the diabetic mice and support the hypothesis that changes in the axonal transport of neurofilaments are responsible for the structural changes seen in early diabetes. Similar changes could also play a role in the development of neuropathy in man.

Acidic fibroblast growth factor stimulates motor and sensory axon regeneration after sciatic nerve crush in the rat.

A time course study in untreated male Sprague-Dawley rats showed that there was no significant difference in the rate of regeneration of motor and sensory axons after a crush injury. Acidic fibroblast growth factor, given topically directly to the site of the crush injury (osmotic minipump for three days) or systemically (i.v. once daily for three days), stimulated the regeneration of motor axons and myelinated sensory axons in the sciatic nerve of the rat. Dose-dependent increases in regeneration distance were seen after 3.6, 36 or 360 ng/day were applied locally and 3 or 10 micrograms/kg per day were given systematically. The greatest effects were achieved with 36 ng/day locally or 10 micrograms/kg per day systematically, when the increase in regeneration distance over three days compared to untreated rats was 47% and 48%, respectively. Administration of heparin vehicle had no significant effect on regeneration. We conclude that since a crush injury has little effect on the endoneurial tubes and supporting cells, the stimulatory effects of acidic fibroblast growth factor on peripheral nerve regeneration seen in this study are likely to be due to a direct acceleration of axonal extension. This is in contrast with the axonal regeneration that occurs across a gap after nerve transection, where axonal extension may be secondary to stimulatory effects on non-neuronal cells providing a supporting "bridge" across the gap. These results suggest that acidic fibroblast growth factor may be clinically useful in the treatment of peripheral neuropathy in man, particularly since systemic treatment for short periods may be effective.