Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nerve growth factor (NGF) is reduced in epidermal keratinocytes in human diabetic skin, and this decrease has been related to dysfunction of cutaneous sensory fibres. In vitro studies show that keratinocytes express both NGF and its high-affinity receptor, trkA, and that NGF may increase keratinocyte proliferation and its own expression via an autocrine loop. However, the level of trkA expression in vivo by keratinocytes in normal and diabetic skin is unknown. We have therefore measured trkA expression in calf skin biopsies from patients with early subclinical diabetic neuropathy and control subjects, using in situ hybridisation combined with image analysis quantification. Expression of trkC was also studied, as its endogenous ligand neurotrophin-3 (NT-3) is related to NGF, and is present in human epidermis. Hybridisation signal was seen for both trkA and trkC localised throughout the epidermal layer of control skin, with a higher density of silver grain deposition observed for trkA mRNA. However, in diabetic epidermis there was a significant increase (P < 0.001) for both trk A (control, 0.178 +/- 0.013; diabetic, 0.304 +/- 0.032; mean silver grain counts/microm2 +/- SEM) and trkC expression (controls, 0.059 +/- 0.004; diabetics, 0.191 +/- 0.010). The up-regulation of epidermal trk receptors may result from decreased autocrine neurotrophin action, and could represent a compensatory mechanism.
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PMID:trkA and trkC expression is increased in human diabetic skin. 919 81

The cholinergic neurons of the basal forebrain system are sensitive to nerve growth factor (NGF), a member of the neurotrophin gene family. Since the cholinergic system is affected early in the course of Alzheimer's disease (AD), it was hypothesized that a deficit in NGF, e.g. reduced neurotrophin uptake by specific receptors, may play a role in neuronal cell death in AD. We quantitated mRNA levels of neurotrophins (NGF, BDNF, NT-3, NT-4/5) and their receptors (trkA, trkB, trkC, p75) in AD postmortem parietal cortex (n = 16) and cerebellum (n = 11). We applied highly sensitive reverse transcription-polymerase chain reaction (RT-PCR) in rapid autopsy derived brain tissue (mean postmortem delay 147+/-96 min., n = 53) to minimize postmortem mRNA variations. In the AD parietal cortex trkA mRNA levels were more than two times lower as compared to controls (n = 16, mean+/-SEM 0.26+/-0.07 units/S12, range, 0-1.78, and n = 11, 0.59+/-0.10 units/S12, range, 0.17-1.10, respectively, P = 0.015). TrkA mRNA levels did not appear to be altered in the AD cerebellum as compared to normal human cerebellum. NGF, BDNF, NT-3, NT-4/5, as well as trkB, trkC and p75 mRNA levels were unchanged in AD parietal cortex and cerebellum as compared to controls. This finding suggests that a reduced expression of the trkA receptor may contribute to impaired NGF-trkA signalling and a reduced transport of NGF in cholinergic neurons. These results reveal a central specific role of the high affinity NGF receptor during neurodegeneration in AD.
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PMID:Decreased trkA neurotrophin receptor expression in the parietal cortex of patients with Alzheimer's disease. 950 43

Neurotrophin-3 (NT-3), a member of the neurotrophin family, has been shown to be necessary for the development of muscle spindle and Merkel cell afferent nerve fibres in animal models. The presence of NT-3 in the suprabasal epidermis, where many unmyelinated sensory fibres terminate, has been shown for the first time. As these fibres are affected in early diabetic neuropathy and a clinical trial of recombinant human NT-3 in diabetic neuropathy is in progress, the concentrations of endogenous NT-3 in skin of 24 patients at different stages of diabetic polyneuropathy have been investigated. NT-3 concentrations, measured with a specific immunoassay, were significantly higher in affected skin biopsies from patients with diabetic neuropathy than matched control skin (diabetic skin 6.32 (1.18) pg/mg v control skin 1.28 (0.05) (mean (SEM)); p<0.004, Mann-Whitney U test), particularly in the later stages. The optical density of NT-3-immunostaining was also significantly greater in the epidermis in diabetic patients (diabetic epidermis 0.30 (0.06) v controls 0.24 (0.01); p<0.02). No correlation was found between individual quantitative sensory tests and the increase of NT-3 concentration. The increase of NT-3 seems to reflect the degree of skin denervation in diabetic neuropathy, and may represent a compensatory mechanism. The concentrations of NT-3 in other peripheral targets deserve study in diabetic neuropathy.
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PMID:Neurotrophin-3 is increased in skin in human diabetic neuropathy. 972 60

During development, neurotrophic factors play an important role in the guidance and outgrowth of axons. Our working hypothesis is that neurotrophic factors involved in the development of axons of a particular CNS tract are among the most promising candidates for stimulating and directing the regrowth of fibers of this tract in the lesioned adult animal. The neurotrophin NT-3 is known to be involved in the target selection of outgrowing corticospinal tract (CST) fibers. We studied the capacity of locally applied NT-3 to stimulate and direct the regrowth of axons of the CST in the lesioned adult rat spinal cord. We also studied the effect of NT-3 application on the functional recovery of rats after spinal cord injury, using the gridwalk test. NT-3 was applied at the site of the lesion dissolved into rat tail collagen type I. Four weeks after spinal cord injury and collagen implantation, significantly more CST fibers had regrown into the collagen matrix containing NT-3 (22 +/- 6%, mean +/- SEM) than into the control collagen matrix without NT-3 (7 +/- 2%). No CST fibers grew into areas caudal to the collagen implant. Despite the absence of regrowth of corticospinal axons into host tissue caudal to the lesion area, functional recovery was observed in rats with NT-3 containing collagen implants.
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PMID:Collagen containing neurotrophin-3 (NT-3) attracts regrowing injured corticospinal axons in the adult rat spinal cord and promotes partial functional recovery. 974 66

In craniofacial surgery, bone is needed to augment misshapen areas and to fill gaps during repair of congenital anomalies and injuries resulting into bone deficiencies. Examples of conditions requiring bone tissue include missing alveolar bone in cleft palates, bony nasal pyramid defects following removal of fistulous tracts or cysts and defects following removal of sinus and mandibular tumors. Moreover, maxillofacial neurosensory deficiencies may be caused by various surgical procedures, such as tooth extraction, osteotomies, pre-prosthetic procedures, excision of tumors or cysts, surgery of TMJ, and surgical treatment of fractures and cleft lip/palate. Therefore, a tissue engineering approach to craniofacial surgery has a crucial importance: the use of various composites with osteoconductive ceramics, polymers, bioactive factors, cells, or a combination of them, offers the possibility of rapid tissue regeneration and integration with the host tissue. In this study, a composite consisting of two well-known biomaterials, collagen/hydroxyapatite (Col/HAp), was used as a drug delivery device for neurotrophin - nerve growth factor beta (NGF beta). This delivery device, enriched with neurogenic-osteogenic factor, was analyzed in vitro and in vivo. It was implanted into calvaria defects of 20 Wistar rats, weighing 200-250 g. Implants were left in place for different periods of time. Controls were as follows: (a) contralateral defect without any implant; and (b) contralateral defect implanted with composite without NGF factor. The rats were euthanized after 30 days, and the implant sites and explants were examined clinically, histologically, SEM and histomorphometrically. Our results evidenced stimulation of periosteal and endocortical woven and lamellar bone formation, with increases in bone mass and decreases in bone marrow. We found that NGF enhanced the remodeling activity in the intracortical region, and induced an increase in the intracortical cavity number and area by the end of the study. In vitro results were in line with in vivo ones. We believe that the composite proposed in this study has considerable advantages in tissue engineering and is very suitable as a biomaterial for the filling of irregular defects in maxillo-facial surgery. Two areas of clinical research will be impacted by this system. The first is pharmaceutical research on drug delivery and high-throughput screening of neurotrophic-osteogenic compounds. Transplantation research is the second area that will benefit from the system.
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PMID:Nerve growth factor beta(NGF beta) delivery via a collagen/hydroxyapatite (Col/HAp) composite and its effects on new bone ingrowth. 1534 79