Search

Ciliary neurotrophic factor has recently been shown to promote the axonal regrowth of retinal ganglion cells into a peripheral nerve graft following an intracranial transection of the optic nerve (approximately 7 mm from the optic disc). It is unclear whether the enhancement of axonal regrowth by ciliary neurotrophic factor application correlates with the enhancement of survival of retinal ganglion cells and/or the up-regulation of expression of growth-associated protein-43 messenger RNA in retinas. The present study evaluated the regenerative capacity of retinal ganglion cells following intraorbital transection of the optic nerve (approximately 1.5 mm from the optic disc) and the attachment of a peripheral nerve to the ocular stump of the optic nerve. In addition, we have determined the survival of retinal ganglion cells and the expression of growth-associated protein-43 messenger RNA in ciliary neurotrophic factor-treated retinas following optic nerve transection. The results showed that in the ciliary neurotrophic factor-treated retinas, the number of retinal ganglion cells which had regrown axons into a peripheral nerve is about four times more than the control. In the axotomized retinas, ciliary neurotrophic factor initiated sprouting of axon-like processes at 14 and 28 days post-axotomy and up-regulated the expression level of growth-associated protein-43 messenger RNA at 7, 14 and 28 days post-axotomy. However, ciliary neurotrophic factor did not prevent the death of axotomized retinal ganglion cells. We suggest that one possible mechanism for the axonal regeneration of axotomized retinal ganglion cells by ciliary neurotrophic factor could be mediated by the up-regulation of growth-associated protein-43 gene expression and not by increasing the pool of surviving retinal ganglion cells after axotomy.

The invention of rotary instruments not only improved the speed of caries removal but also the destruction of sound tooth substance. Hence, as early as the 1950s, there were attempts to develop a less invasive technique, such as the air-abrasive and ultrasonic technique, for the purpose of caries removal. The proposed use of air-polishing was published in the early 1980s. Subsequent better understanding of the carious process saw the introduction of the enzyme technique in the late 1980s. Other techniques, such as chemomechanical caries removal and laser systems, have also been attempted and researched during the last four decades to minimise the unnecessary removal of sound tooth substance, although these and other techniques reviewed in this article have not yet superseded the use of rotary instruments. Furthermore, the concept of micro-cavity preparation developed in recent years and the introduction of acid-etch techniques, resin bonding and the use of glass-ionomer cements have also revolutionised the principles of cavity preparation in conservative dentistry. This article reviews the development of these various caries removal techniques and instrumentation and the evolutionary philosophies of cavity preparation promulgated over the last century or so.

The low-affinity neurotrophin receptor p75(NTR), or p75, is a 75-kDa cell surface glycoprotein that binds all neurotrophins with similar affinity and is thought to help to ensure the specificity of each neurotrophin. In order to better understand the role of p75 and how it is involved in the neurotrophic effects in the retina, we have examined its cellular localization in the adult rat retina by immunocytochemistry at both light and electron microscopic levels. The similarity between the staining pattern of p75 and that of the distribution of Müller cell processes, as marked by antibodies against S-100 and vimentin, suggests that p75 may be on the Müller cell processes and not on the retinal ganglion cells (RGCs) as previously reported. The failure to detect p75 immunoreactivity on Fluoro-Gold retrogradely labeled RGCs in the radially sectioned retinae also indicates that it is not expressed on RGCs. The results from the light microscopic immunohistochemical studies are supported at the ultrastructural level, showing that p75-immunopositive staining is localized on Muller cell processes and not on RGC bodies. Muller cell processes not only form the inner limiting membrane but also partially wrap around the RGC bodies. Our results lead us to conclude that the previously reported immunopositive staining of p75 on RGCs might belong to the surrounding Miller cell processes. Thus, the pathway of neurotrophic effects on RGCs might be, at least partially, through a glial-neuronal pathway rather than on RGCs directly.

The mammalian visual system, particularly retinal ganglion cells, has been used for studying the functions of neurotrophic factors on neurons for many years. The major biological effects of neurotrophic factors on retinal ganglion cells observed so far are the promotion of viability and axonal regeneration. However, there are still some controversies regarding the effects of neurotrophic factors on retinal ganglion cells in the literature. This review is aimed to summarize the available information on the biological actions of these neurotrophic factors on survival and axonal regeneration of retinal ganglion cells and the expressions of neurotrophic factor receptors in the retina. Generally, brain-derived neurotrophic factor, neurotrophin-4/5, fibroblast growth factor and glial cell line-derived neurotrophic factor increase the survival of retinal ganglion cells while the effect of ciliary neurotrophic factor on the viability of adult retinal ganglion cells is controversial. The ciliary neurotrophic factor is the only effective factor in promoting long distance axonal regeneration of retinal ganglion cells whereas brain-derived neurotrophic factor and neurotrophin-4/5 only enhance neurite sprouting within the retina.

Retinal ganglion cells (RGCs) and their projections in the optic nerve offer a convenient model to study survival and regeneration of mammalian central nervous system (CNS) nerve cells following injury. Possible factors affecting the death of RGCs following axotomy and various approaches to rescue the axotomized RGCs are discussed. In addition, two main strategies currently used to enhance axonal regeneration of damaged RGCs are described. The first focuses on overcoming the unfavorable extrinsic CNS environment and the second concentrates on upregulating the intrinsic growth potential of RGCs. Thus, the failure or success of RGC axonal regrowth after injury depends on the complicated interplay between the extrinsic and intrinsic factors.

Percutaneous transluminal coronary angioplasty was performed on 2 patients, each having an anomalous origin of the right coronary artery with anterior-superior orientation. Each patient had experienced post-infarction angina after an inferior wall myocardial infarction without antecedent thrombolytic therapy. The procedures were successfully performed with appropriate selection and manipulation of the guiding catheter. Our findings indicate that the Amplatz left catheter is the guiding catheter of choice in catheterizing a right coronary artery of anomalous origin with anterior-superior orientation.

Learning in dental education has long been a subject of academic research. There are different types of student learning which directly or indirectly contribute to the learning outcomes. In this paper, the various classifications of different types of learning; superficial, deep, individual, collaborative and resource-based learning are explored. In order to achieve the learning objectives, different teaching methods such as group-work, rôle-play and problem-based learning are employed. The types of resources used in present day teaching are diverse and multiple: such as print-based, computer-based technologies and audio-visual technologies. In order to assess the effectiveness of such teaching, different methods of assessment have been adopted for use in higher education. In the context of good teaching in higher education, there are a number of constraints placed upon the individual and the institution. These constraints are discussed and recommendations made whereby they may be overcome.

Objectives and Methods: An in vitro study has been carried out on the chemomechanical removal of caries in deciduous and permanent teeth. The aims of the study were to compare the efficacy of caries removal by various chemical agents including N-monochloro-DL-2-aminobutyrate (NMAB) and NMAB containing urea (NMAB-urea), to compare the efficacy on permanent and deciduous teeth and to study the dentinal surfaces produced., Results: The addition of urea to NMAB resulted in an improvement in the efficacy of caries removal. Sodium hypochlorite, saline and urea alone were also studied as caries removal agents, but were not significantly different from NMAB. Chemomechanical caries removal solutions were more effective in removing caries from deciduous teeth than from permanent teeth, especially in terms of the volume of solution used. The improvement on addition of urea was found to be greater in deciduous than in permanent teeth, the number of deciduous teeth with 'complete cares removal' being increased by about 25%. The dentinal surfaces of the cavities prepared using these solutions and in which 'complete caries removal' had been achieved were studied by scanning electron microscopy. Generally after treatment with NMAB or NMAB-urea, the surface appearance was very uneven with many undermined areas. NMAB-urea produced a 'cleaner' surface compared with that produced by NMAB alone., Conclusions: NMAB appears to be potentially more effective and clinically more useful in removing caries in deciduous teeth than in permanent teeth, and the addition of urea may enhance its efficacy, especially in the treatment of paediatric dental patients.

Although the dentine remaining after chemomechanical caries removal appears sound by normal clinical criteria, no definitive evidence has yet been obtained to confirm that the dentine surface is in fact mineralised. The aim of this study was to use backscattered electron (BSE) imaging and electron probe micro-analysis (EPMA) to ascertain the level of mineralisation of the dentine remaining in cavities prepared by this technique. Carious dentine was removed from carious lesions by means of N-monochloro-DL-2-aminobutyric acid (NMAB) or NMAB containing 2 mol/l urea. Sections of teeth in which caries removal was complete by normal clinical criteria were examined by EPMA and BSE. Dentine adjacent to the pulp was found to be less mineralised than the surrounding dentine. Although the superficial layer of dentine remaining on the cavity floors frequently appeared to have a slightly reduced mineral content, the results clearly indicated that there was no significant difference between this dentine and the underlying sound dentine.

The specificity of two caries detector dyes (0.5% basic fuchsin and 1.0% acid red) was investigated in vitro using extracted human permanent and deciduous teeth. Although the dyes stained carious dentine, sound circumpulpal dentine and the enamel-dentine junction could also be stained. Backscattered electron imaging showed that the level of mineralisation in these two parts of the tooth was lower than in normal dentine. Susceptibility to dye staining therefore appears to be a feature of reduced mineral content rather than being specific for a carious lesion. Whilst use of basic fuchsin should be avoided in view of its carcinogenic potential and ability to stain sound coronal dentine, acid red should also be used with caution and its use on the pulpal surface of deep cavity preparations would appear to be contraindicated. Use of these dyes may result in the unnecessary removal of sound dentine.

Nerve growth factor (NGF) is known to be essential for survival and maintenance of sympathetic ganglia and of embryonic sensory ganglia of neural crest origin. The present study examined the physiological and pharmacological roles of NGF in the postnatal development of sensory neurons in the dorsal root ganglion (DRG). In contrast to what is generally stated in the literature, administration of NGF antiserum to newborn rats for a period of 7 days resulted in a significant (approximately 20%) reduction of neuronal number in the lumbar DRG. Size spectrum analysis of surviving neurons revealed a shift toward larger sizes, presumably due to a preferential loss of small cells. The number of neurons in the L5 DRG was studied at various times after unilateral sciatic nerve crush in 1-day-old rats. Axotomy resulted in a substantial loss (40 to 50%) of neurons in the immature DRG. Administration of NGF antiserum to animals with axotomized DRG did not increase cell death when compared with the axotomized controls. However, the number of neurons in the antiserum-treated ganglia decreased by the same percentage (20%) when compared with the control serum-treated ganglia before and after axotomy. Treatment with NGF initially prevented the loss of neurons in the axotomized DRG. However, some neurons died during the first week despite continued NGF administration; and, subsequent to NGF withdrawal, neuronal number decreased to the same level as in control animals. Thus, removal of exogenous NGF resulted in the death of the sensory neurons which had been maintained.(ABSTRACT TRUNCATED AT 250 WORDS)

The response of dorsal root ganglia (DRG) neurons to NGF deprivation and to axotomy was examined in adult guinea pigs. The success of NGF deprivation by means of an autoimmune approach was monitored by the measurement of serum antibody titer levels against guinea pig NGF with the standard bioassay for NGF activity. That the antibody produced NGF deprivation was confirmed by histologic evidence of neuronal atrophy and apparent cell loss in sections of the superior cervical ganglia (SCG) and by marked decreases (65-80%) of SCG neurotransmitter-synthesizing enzyme activity levels. By using the autoimmune approach a new source of guinea pigs was found which consistently produced high titers of cross-reacting anti-NGF antibodies. Experiments were designed to examine the response of the sensory neuron to injury while chronically deprived of NGF. Total neuronal counts in the sixth lumbar DRG 98 days after sciatic nerve crush showed no difference between NGF-deprived and control ganglia. Measurement of the size spectrum of DRG neurons showed evidence of atrophy of the NGF-deprived neurons in both the uninjured and axotomized side compared to respective controls. The mean volume of uninjured sensory neurons measured in the NGF-deprived guinea pigs was decreased 27.7% (P less than .05) compared with that of control guinea pigs. The degree of regeneration 6 days following a nerve crush was the same in NGF-deprived sensory neurons and in controls when measured by the "pinch test" and by isotope-labeled axonal transport studies.(ABSTRACT TRUNCATED AT 250 WORDS)

The retrograde axonal transport of intravenously administered [125I]nerve growth factor ([125I]NGF) was examined in ileal mesenteric nerves maintained for short periods in vitro. [125I]NGF was injected systemically, and at various times thereafter mesenteric pedicles were ligated and incubated in vitro in Krebs-Henseleit medium under a number of different conditions. Retrogradely transported [125I]NGF began to accumulate distal to the ligature after an initial lag period and increased in a linear fashion for 3-4 h. The amount of retrogradely transported [125I]NGF was proportional to the length of the ileum innervated by each pedicle, which allowed for comparison of ileal segments of different lengths. Retrograde axonal transport of [125I]NGF was inhibited by vinblastine, colchicine and incubation in the cold, and was decreased by agents that interfere with oxidative or glycolytic metabolism. The accumulation of retrogradely transported [125I]NGF in ileal mesenteric nerves of 1-9 day streptozotocin diabetic animals placed in an in vitro bath containing normal (5.5 mM) glucose was decreased 40% compared to control animals. The induction of diabetes in vivo resulted in a greater decrease in the early phases of [125I]NGF export from ileal mesenteric nerve terminals compared to later phases. Ileal mesenteric nerve segments derived from untreated controls were incubated in vitro in media containing increased concentrations of glucose (27.5 and 50 mM) without reproducing the NGF transport defect found in diabetic animals.

We have previously demonstrated a reproducible axonopathy, involving but not confined to sympathetic neurons, which involves selectively the mesenteric nerves of chronically diabetic rats. We describe a series of experiments aimed at correlating changes in the retrograde transport of 125I-nerve growth factor (125I-NGF) with development of the lesions. 125I-NGF was injected systemically and the time course of accumulation compared in superior cervical ganglion (SCG) and superior mesenteric ganglion (SMG). 125I-NGF accumulated in the SCG with a sharp peak at 12 h, whereas in the SMG, accumulation reached a plateau, remaining at relatively constant amounts for 8 h before decreasing. There was a marked decrease in the accumulation of 125I-NGF (averaging 44% in 11 separate experiments) in the SMG at early times (approximately 12 h). These decreases were seen in animals diabetic for times ranging from 2 days to 10 mo. In contrast, no consistent decrease was observed in the SCG. The time course of 125I-NGF accumulation was unaltered in the SCG of diabetic rats but was clearly retarded in the SMG of diabetic animals. Morphometric examination of the SMG of diabetic animals and controls showed little or no atrophy or neuron loss due to diabetes. We conclude that decreases in the retrograde transport of NGF occur selectively in those ganglia (SMG) serving the alimentary tract in which mesenteric nerves develop distal axonopathy, but not in ganglia whose nerves do not ultimately develop such lesions (SCG). The decreases in retrograde transport precede the development of morphologic lesions in this system. These results are consistent with the suggestion that impairment of axonal transport may play a role in the development of axonopathy.

The distribution of nerve growth factor receptors in the lumbar spinal cord of the rat was studied with autoradiographic and immunohistochemical techniques: [125I]nerve growth factor and specific monoclonal antibody (Mab 192) against nerve growth factor receptor were used to localize nerve growth factor binding sites. The distributions of nerve growth factor binding sites with highest density within the superficial layers (laminae I and II) of the dorsal gray matter were virtually identical as demonstrated by these two ligands; this suggests that Mab 192 can be used as a specific probe to identify nerve growth factor receptors in rat nervous system. Nerve growth factor receptor binding sites, as demonstrated by autoradiography, were also found in longitudinal bundles of fibers running dorsolaterally in the lateral funiculus. However, no immunoreactivity was detected in these areas by immunohistochemistry. No specific binding was found in the dorsal horn when [125I]nerve growth factor was co-injected with unlabeled nerve growth factor or after incubation with nonspecific monoclonal antibody. Dorsal root section produced a complete loss of nerve growth factor-specific labeling pattern throughout laminae I-II of the spinal cord. This suggests that nerve growth factor receptors are localized on the nerve terminals of primary afferent fibers which synapse in the region of the spinal cord. The presence of nerve growth factor binding sites in the dorsal horn of the spinal cord is consistent with the possibility that nerve growth factor, or a nerve growth factor-like substance, derived from the central nervous system, may have a role in trophic support of dorsal root ganglion neurons.

The dynamics of the retrograde transport of [125I] nerve growth factor (NGF) and horseradish peroxidase (HRP) in dorsal root ganglion (DRG) neurons were studied in rats. After injection of [125I]NGF or HRP into crushed sciatic nerve, labelling was examined in spinal nerves, dorsal root ganglia, dorsal roots and spinal cord. Retrograde transport of either [125I]NGF or HRP was first observed in DRG neurons 6 h after injection: The maximal rate of transport (7 mm h-1) was similar for both proteins. Significant differences in the sizes of DRG neurons labelled by [125I]NGF were observed and were dependent upon survival time. No such difference was seen in HRP-injected animals. At 6 h after injection, 60% of all the HRP-labelled cells had a diameter of more than 25 micron, whereas 90% of all the [125I]NGF-labelled neurons had a diameter of less than 25 micron. With increasing survival times there was a gradual shift in the size of [125I]NGF-labelled neurons towards larger diameters. Thus, 24 h after the [125I]NGF injection, 83% of the labelled cells had a diameter greater than 25 micron. The data suggest that small diameter neurons retrogradely transport and turnover NGF faster than larger diameter neurons. There was a preferential accumulation of silver grains in small DRG neurons (mean diameter 25 micron) at early survival times (4 and 8 h); at the later survival time (24 h) the reverse was observed, i.e. larger neurons (mean diameter 42 micron) were labelled. In contrast, the mean diameter of HRP-labelled neurons remained constant (30 micron) at all times after injection. The total number of neurons ultimately labelled (approximately 80-85%) appeared to be the same with both tracers. In addition, the lack of transganglionic transport of NGF into the spinal cord and the short time span of the observable accumulated radioactivity in DRG neurons suggest the rate of degradation of transported NGF seems to be faster than HRP. As a practical matter, these data indicate that observing cells within DRG which accumulate retrogradely transported [125I]NGF at any one time gives an inaccurate picture of the size properties of cells capable of transporting the ligand.

Primary sensory neurones in cranial and dorsal root ganglia (DRG) of adult animals are generally thought to be maintained through connections with their peripheral (but not central) targets by trophic factor(s) other than nerve growth factor (NGF). Damage to the peripheral process of sensory neurones results in a dramatic response or even death of the neurones, whereas axotomy (cutting) of the central process does not initiate profound reaction in these neurones. The development and maintenance of neurones are highly dependent on a supply of trophic agents produced by targets and retrogradely transported via the peripheral process to the cell body. NGF deprivation in fetal rodents produced either by exogenously administered antibodies or by those of maternal origin, results in death of DRG and of some cranial sensory neurones. However, as chronic NGF deprivation in neonatal or adult rodents produces little or no cell death, it has been assumed that some other trophic factor(s) derived from the peripheral target sustains sensory neurones in postnatal life. By inducing NGF deprivation by autoimmunizing guinea pigs with mouse NGF and/or by cutting the central root (process) of a DRG, we demonstrate here that under certain conditions DRG neurones require NGF and centrally derived trophic support. Our results indicate that sensory neurones are maintained by the trophic support provided by both peripheral and central targets. This support is mediated by NGF and other as yet unidentified trophic factors. The relative importance of the two target fields and NGF compared with other trophic factors changes during development.

Injury to the peripheral processes produces a profound cell loss (40-50%) in the dorsal root ganglion of newborn rats. Although division of central processes produces little or no cellular change in sensory ganglion of adult animals, no information has been available on the effect of dorsal root section in developing dorsal root ganglion. We show that 6 days after dorsal rhizotomy on newborn rats, there is a 50% decrease in neuronal number in L5 dorsal root ganglion. A combined central and peripheral lesion of the sensory process results in a greater decrease in neuronal number (70%). Both of these effects can be prevented by the concomitant treatment with nerve growth factor. We also demonstrate that 125I-Ia-labeled nerve growth factor is retrogradely transported with high selectivity from the spinal cord to the dorsal root ganglion via the dorsal roots. The results indicate that trophic support for developing sensory neurons is provided through the central processes. This is presumably due to the uptake and retrograde transport of a trophic factor by the terminals of the central processes. The data suggest that nerve growth factor may be the trophic factor.

Axonal outgrowth following a crush of the goldfish optic nerve was enhanced if nerve growth factor (NGF) was administered by intraocular injection or by local application to the lesion site. Various forms of NGF (beta, 2.5S and 7S) were effective, producing a 20-40% decrease in the time required for recovery of the startle reaction to a bright light. A corresponding increase in axonal outgrowth was revealed by histological examination of the optic nerves. The effect produced by a single intraocular injection given at the time of the lesion was not further increased by subsequent injections. Up to 14 days after the lesion, the size of the retinal ganglion cell bodies and the incidence of nucleoli detectable by light microscopy were not affected by the NGF treatment.

Previous experiments have shown that nerve growth factor (NGF) enhances regeneration of goldfish optic nerve after local application of NGF at the site of the lesion. However, the site and mechanism of action of NGF are not yet known. One possibility is that NGF is taken up at the site of the lesion and retrogradely transported to the cell bodies of the retinal ganglion cells and thereby exerts its trophic effects. The present work was carried out to assess the role of retrograde transport of NGF in this enhanced regeneration of goldfish retinal ganglion cells. In intact retinal ganglion cells of the goldfish, 125I-labeled NGF was found not to be retrogradely transported from the optic tectum to the retina, suggesting that retinal ganglion cells do not possess specific NGF receptors. However, if [125I]NGF was injected at the site of an optic nerve lesion at the time of lesion, [125I]NGF was retrogradely transported from the site of a lesion of the optic nerve to the cell body of retinal ganglion cells. The accumulated radioactivity was shown to be intact NGF by SDS-PAGE. The ability of NGF to decrease the time required for recovery of visual function was observed only when NGF was administered at the time of the injury. Likewise, no transport of [125I]NGF was observed when it was injected at the crush site 16 hr or longer after crush. Thus, there is a temporal correlation between the ability of intact [125I]NGF to be retrogradely transported from a lesion site to the retina and the regenerative effect of NGF. Autoradiography showed that the [125I]NGF accumulated only in retinal ganglion cells. The transport of NGF in the lesioned goldfish visual system was not specific for NGF in that other proteins (cytochrome c, bovine serum albumin) were transported equally well. Likewise, transport of [125I]NGF was not prevented by concomitant administration of excess unlabeled NGF. The retrograde transport of [125I]NGF therefore was not selective and did not appear to be mediated by specific NGF receptors in this system. This nonspecific transport of [125I]NGF did not occur in the axotomized spinal motor neurons in the neonatal or adult rat or in the newt. However, receptor-mediated transport is seen in lesioned sensory neurons in both species.(ABSTRACT TRUNCATED AT 400 WORDS)

We have previously demonstrated the reproducible occurrence of dystrophic axonopathy and a defect in the retrograde axonal transport of 125I-nerve growth factor (125I-NGF) involving postganglionic sympathetic axons in the alimentary tract of rats with chronic streptozocin (STZ)-induced diabetes. To avoid complexities inherent in monitoring the accumulation of 125I-NGF in the superior mesenteric ganglion as a measure of retrograde transport in the peripheral axons of the extensive alimentary territory, we have examined retrograde axonal transport of 125I-NGF directly in ileal mesenteric nerves. 125I-NGF was injected systemically, and 2-2.5 h later ileal mesenteric nerve pedicles were ligated in vivo for various intervals. Retrogradely transported 125I-NGF in rat mesenteric nerves was measured distal to a ligature placed on the ileal mesenteric pedicle. Transport-unrelated processes, such as mechanical compression or bleeding at the site of ligation, did not contribute significantly to accumulation measured in this fashion. Accumulation of retrogradely transported 125I-NGF at the ligature began 4 h after ligation and remained linear for approximately 12 h. The amount of retrogradely transported 125I-NGF accumulating distal to the ligature reflected the length of the ileal segment served by the pedicle, which allowed the standardization of accumulation based on length of ileum innervated. The results of several experiments showed that 125I-NGF transport originated largely from nerve terminals within the ileal wall with a smaller component from extramural sites, probably terminals within the walls of blood vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

The retrograde axonal transport of intravenously (i.v.) administered 125I-nerve growth factor (125I-NGF) was examined in mesenteric nerves innervating the small bowel of rats with streptozocin (STZ) diabetes using methods described in detail in the companion article. The accumulation of 125I-NGF distal to a ligature on the ileal mesenteric nerves of diabetic animals was 30-40% less than in control animals. The inhibition of accumulation of 125I-NGF in diabetic animals was greater at a ligature tied 2 h after i.v. administration than at a ligature tied after 14 h, which suggests that the diabetic animals may have a lag in initiation of NGF transport in the terminal axon or retardation of transport at some site along the axon. The 125I-NGF transport defect was observed as early as 3 days after the induction of diabetes, a time before the development of structural axonal lesions, and did not worsen at later times when dystrophic axonopathy is present. Both the ileal mesenteric nerves, which eventually develop dystrophic axonopathy in experimental diabetes, and the jejunal mesenteric nerves, which never develop comparable structural alterations, showed similar 125I-NGF transport deficits, suggesting that the existence of the transport abnormality does not predict the eventual development of dystrophic axonal lesions. Autoradiographic localization of 125I-NGF in the ileal mesenteric nerves of animals that had been diabetic for 11-13 mo demonstrated decreased amounts of 125I-NGF in transit in unligated paravascular nerve fascicles. There was, however, no evidence for focal retardation of transported 125I-NGF at the sites of dystrophic axonal lesions.