Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0599766 (functional recovery)
 13,441 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenine nucleotides speed structural and functional recovery when administered after experimental renal injury in the rat and stimulate proliferation of kidney epithelial cells. As cell migration is a component of renal regeneration after acute tubular necrosis, we have used an in vitro model of wound healing to study this process. High density, quiescent monkey kidney epithelial cultures were wounded by mechanically scraping away defined regions of the monolayer to simulate the effect of cell loss after tubular necrosis and the number of cells that migrated into the denuded area was counted. Migration was independent of cell proliferation. Provision of adenosine, adenine nucleotides, or cyclic AMP increased the number of migrating cells and accelerated repair of the wound. Other purine and pyrimidine nucleotides were not effective. Arginine-glycine-aspartic acid-serine peptide, which blocks the binding of extracellular fibronectin to its cell surface receptor, completely inhibited migration in the presence or absence of ADP. Very low concentrations of epidermal growth factor (K0.5 approximately 0.3 ng/ml) stimulated migration, whereas transforming growth factor-beta 2 was inhibitory (Ki approximately 0.2 ng/ml). Thus, adenosine and/or adenine nucleotides released from injured or dying renal cells, or administered exogenously, may stimulate surviving cells in the wounded nephron to migrate along the basement membrane, thereby rapidly restoring tubular structure and function.
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PMID:Adenine nucleotides stimulate migration in wounded cultures of kidney epithelial cells. 163 17

The cytokine leukemia inhibitory factor (LIF) favors the survival and growth of axons in vitro and in vivo. Fibronectin has been shown to enhance nerve regeneration when added in combination with various growth factors including LIF. The goal of this study was to evaluate the effect of LIF plus fibronectin on the regeneration of transected nerve and functional recovery of reinnervated skeletal muscle, in one experimental model of peripheral nerve repair, at two recovery times. The rat sciatic nerve was cut at mid-thigh level and a silicone cuff containing either saline (control), LIF, or LIF plus fibronectin (L+F) was used to bridge the proximal and distal nerve stumps leaving a 1 cm gap between them. Rats were then explored at 6 or 12 weeks following the initial surgery. Regenerating nerves were assessed by measuring the diameter of myelinated axons, conduction velocity, and number of myelinated fibers. Muscle reinnervation was assessed by measuring muscle mass, force of contraction, and histologically for changes in muscle fiber type (type I and type II). In this report we demonstrate that at 6 weeks there were significant increases in 1) nerve conduction velocity, 2) myelinated axon diameter, and 3) number of myelinated axons over that of control (saline-treated) animals. Both LIF groups demonstrated a shift in type II muscle fiber area compared to saline-treated controls, with the L+F group having a significant increase in muscle mass. At 12 weeks there was an improved recovery over and above that demonstrated at 6 weeks. Muscle mass was 65% and 42% greater than control for LIF and L+F, respectively. Force of contraction, conduction velocity, myelinated fiber number, and diameter were also significantly greater for both LIF- and L+F-treated rats than saline-treated rats. These results demonstrate that LIF significantly improves the regeneration of damaged peripheral nerves and the preservation of muscle viability, resulting in greatly enhanced recovery of skeletal muscle function.
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PMID:Leukemia inhibitory factor enhances the regeneration of transected rat sciatic nerve and the function of reinnervated muscle. 900 51

Following injury to the central nervous system, an astroglial scar forms that is thought to impede neuronal regeneration and recovery of function. It is our hypothesis that inflammatory cytokines act upon astrocytes to alter their biochemical and physical properties, which may in turn be responsible for failed neuronal regeneration. We have therefore examined the interactions of two cytokines with prominent actions following injury, interferon-gamma (IFN-gamma) and basic fibroblast growth factor (FGF2), in modulating the extracellular matrix and proliferation of astrocytes in culture. We also evaluated the effects of these cytokines on the ability of astrocytes to support the growth of neurites. IFN-gamma significantly inhibited the proliferation of rat cortical astrocytes both in serum-free and serum-containing media as measured by [3H]thymidine incorporation. Furthermore, IFN-gamma also antagonized FGF2-induced proliferation. In parallel, IFN-gamma reduced the levels of the ECM molecules tenascin, laminin, and fibronectin as evaluated by Western blot analysis and immunocytochemistry. Similarly, IFN-gamma also antagonized FGF2-induced tenascin formation. While IFN-gamma-pretreated astrocyte monolayers did not differ from control in their ability to support neurite outgrowth of cortical neurons, it antagonized the enhancement of neurite outgrowth on FGF2-treated monolayers. We demonstrate that IFN-gamma did not alter signal transduction through the FGF2 receptor down to the phosphorylation of mitogen-activated protein kinase, suggesting that the interaction is at the level of transcriptional regulation or that an alternate pathway is involved. These results support the hypothesis that inflammatory cytokines interact to modulate several facets of the gliotic response and such interactions may be important in creating the biochemical and physical properties of the glial scar.
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PMID:Inflammatory cytokines interact to modulate extracellular matrix and astrocytic support of neurite outgrowth. 941 38

The long-term prognosis of patients with ischemic cardiomyopathy is highly variable, depending on the extent of myocardial viability and the success and completeness of the revascularization techniques used. Other important factors include left ventricular function, extent of coronary artery disease (CAD), and patient age. Chronic left ventricular dysfunction in ischemic cardiomyopathy is the result of a mixture of scarred as well as hibernating myocardium. In fact, most patients have both scarring and hibernation in different regions. Transmural biopsies of dysfunctional segments reveals that recovery of function is inversely proportional to the extent of fibrosis and that endocardial fibrosis extending over 30% of the myocardial thickness precludes recovery of function.Nagueh et al. [1] evaluated the relation of contractile reserve and thallium uptake in hibernating myocardium to myocardial structure in humans. The authors found that segments with postoperative functional recovery had more wall thickening at low-dose dobutamine echocardiography (DE), higher thallium uptake, and less fibrosis (2.0 vs 28%) than those segments without recovery. Also, segments with viability on DE had less fibrosis, less vimentin and fibronectin, more glycogen, and higher thallium uptake, than those segments without viability. Importantly, segments viable by single-photon emission computed tomography (SPECT) and DE had significantly less fibrosis (1%) than those viable by only one of the two techniques. In this review, we discuss recent developments in the detection of myocardial viability, including echocardiography, nuclear cardiac imaging, magnetic resonance imaging (MRI), and other techniques.
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PMID:Myocardial viability: recent developments in detection and clinical significance. 1158 65

Cirrhosis is one of the most common causes of mortality worldwide, because hepatic dysfunction constitutes a potentially lethal condition. Having demonstrated the hepatoprotective effect of adenosine against CCl(4)-induced cirrhosis, the present study was aimed at assessing adenosine's effect on an already-established micronodular cirrhosis. Chronic administration of CCl(4) (10 weeks) induced a cirrhotic state, characterized by increased liver fibronectin and collagen types I and III content, enhanced expression of alpha-1 (I) collagen mRNA, portal hypertension, and liver dysfunction. After CCl(4) discontinuation (5 weeks), increased persitance of alpha-1 (I) collagen mRNA expression and deposition, enhanced proline incorporation into collagen and prolyl hydroxylase activity evidenced active fibrogenesis. Several weeks after CCl(4) withdrawal, deposited collagen showed an enhanced type I/III ratio, which was associated with deficient collagenolytic activity in cirrhotic livers. Liver expression of some metalloproteinases (MMPs) and of tissue inhibitors of MMPs (TIMPs) also indicated decreased collagen breakdown in cirrhotic livers. Parameters indicative of oxidative stress (mainly protein oxidation) were persistently augmented. These events were coincident with diminished regenerative capacity of the cirrhotic liver. Intraperitoneal adenosine administration to CCl(4)-induced cirrhotic rats blocked active fibrogenesis and increased the collagen degradation (most probably by decreasing liver TIMPs levels), normalizing collagen-type ratios. In addition, the nucleoside promoted an effective hepatocyte's proliferation in the cirrhotic liver and accelerated normalization of parameters indicative of liver function and oxidative stress. Thus, adenosine readily reversed an experimental cirrhosis through stimulating liver collagenolytic and proliferative capacities, as well as by accelerating functional recovery.
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PMID:Adenosine reverses a preestablished CCl4-induced micronodular cirrhosis through enhancing collagenolytic activity and stimulating hepatocyte cell proliferation in rats. 1158 63

Multipotential stem cells are an attractive choice for cell therapy after traumatic brain injury (TBI), as replacement of multiple cell types may be required for functional recovery. In the present study, neural stem cells (NSCs) derived from the germinal zone of E14.5 GFP-expressing mouse brains were cultured as neurospheres in FGF2-enhanced medium. When FGF2 was removed in vitro, NSCs expressed phenotypic markers for neurons. astrocytes, and oligodendrocytes and exhibited migratory behavior in the presence of adsorbed fibronectin (FN). NSCs (10(5) cells) were transplanted into mouse brains 1 week after a unilateral, controlled, cortical contusion (depth = 1 mm, velocity = 6 m/s, duration = 150 ms) (n = 19). NSCs were injected either directly into the injury cavity with or without an injectable FN-based scaffold [collagen I (CnI)/FN gel; n = 14] or into the striatum below the injury cavity (n = 5). At all time points examined (1 week to 3 months posttransplant), GFP+ cells were confined to the ipsilateral host brain tissue. At 1 week, cells injected into the injury cavity lined the injury penumbra while cells inserted directly into the striatum remained in or around the needle track. Striatal transplants had a lower number of surviving GFP+ cells relative to cavity injections at the 1 week time point (p < 0.01). At the longer survival times (3 weeks-3 months), 63-76% of transplanted cells migrated into the fimbria hippocampus regardless of injection site, perhaps due to cues from the degenerating hippocampus. Furthermore, cells injected into the cavity within a FN-containing matrix showed increased survival and migration at 3 weeks (p < 0.05 for both) relative to injections of cells alone. These results suggest that FGF2-responsive NSCs present a promising approach for cellular therapy following trauma and that the transplant location and environment may play an important role in graft survival and integration.
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PMID:Fibronectin promotes survival and migration of primary neural stem cells transplanted into the traumatically injured mouse brain. 1207 94

PURPOSE: A major reason for the poor functional recovery after peripheral nerve injury is the outgrowth of supernumerary axonal branches at the lesion site. Projecting within several nerve fascicles, the branches of one axon often re-innervate synchronously muscles with antagonis-tic functions and impair any coordinated activity. We hypothetized that accelerated axonal elongation through extracellular matrix proteins fos-tering neurite outgrowth might reduce axonal branching and improve recovery of function. METHODS: In a control group of rats, ramus zygomaticus, ramus buccalis, and ramus marginalis mandibulae of the facial nerve were transected and the stumps labeled with DiI, Fluoro-Gold (FG), and Fast Blue (FB). RESULTS: Neuron counts showed that the zygomatic ramus contained axons of 204 +/- 88 DiI-labeled motoneurons in the dorsal facial subnu-cleus. No perikarya were labeled by 2 or 3 tracers. After transection and suture of the facial nerve trunk, the zygomatic ramus contained axons of 328 +/- 50 motoneurons dispersed throughout the whole facial nucleus. The occurrence of double-labeled (DiI+FG and DiI+FB) motoneu-rons showed that about 30 % of all axons in the zygomatic ramus had a twin branch projecting within the buccal and/or mandibular ramus. CONCLUSIONS: Entubulation of transected facial nerve in a silicone tube containing phosphate buffered saline, collagen type I, laminin, fibronectin, or tenascin did not reduce the portion of double-labeled motoneurons. We conclude that (i) axonal branching follows a rather con-stant pattern regardless of changes in the local microenvironment; (ii) despite their known effect to support neurite outgrowth, all tested extra-cellular matrix proteins do not suppress axonal branching in the rat facial nerve model.
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PMID:Local application of extracellular matrix proteins fails to reduce the number of axonal branches after varying reconstructive surgery on rat facial nerve. 1267 Dec 14

We devised a novel nerve prosthesis composed of an elastomeric gelatinous tube and multifilament gelatinous fibers, both of which were prepared from styrene-derivatized gelatin, which allows in situ formation of a bioactive substance-incorporated gel. An in vitro study showed that the axonal regeneration potential of a photocured gelatin layer impregnated with laminin, fibronectin, and NGF was almost comparable with that of coated Matrigel. A nerve conduit and fibers prepared from photoreactive gelatin was subjected to visible-light irradiation with rotation in the presence of camphorquinone as a photoinitiator using a custom-designed apparatus. A sample of transparent gelatinous conduit with an inner diameter of 1.2 mm and a wall thickness of 0.6 mm and gelatin fibers ranging from 10 to 100 pm in diameter were produced. The photocured elastomeric gelatinous tube was flexible and had structural integrity that allowed mechanical handling without breaking. A novel nerve guidance prosthesis composed of tubes packed with fibers was assembled. This photofabrication technology may enable the design of a tailor-made shape and rapid morphogenesis and functional recovery of damaged nerve tissue.
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PMID:Photoconstructs of nerve guidance prosthesis using photoreactive gelatin as a scaffold. 1295 22

We investigated whether neurotrophin-4 (NT-4) and brain-derived neurotrophic factor (BDNF) affected the reinnervation of slow and fast motor units. Neurotrophin-impregnated or plain fibronectin (FN) conduits were inserted into a sciatic nerve gap. Fast extensor digitorum longus (EDL) and slow soleus muscles were collected 4 months postsurgery. Muscles were weighed and fibre type proportion and mean fibre diameters were derived from muscle cross-sections. All fibre types in muscles from FN animals were severely atrophied and this correlated well with type 1 fibre loss and atrophy in soleus and type 2b loss and atrophy in EDL. Treatment with NT-4 reversed soleus but not EDL mass loss above the FN group by significantly restoring type 1 muscle fibre proportion and diameters towards those of normal unoperated animals. BDNF did not increase muscle mass but did have minor effects on fibre type and diameter. Thus, NT-4 significantly improved slow motor unit recovery, and provides a basis for therapies intended to aid the functional recovery of muscles after denervating injury.
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PMID:Effect of NT-4 and BDNF delivery to damaged sciatic nerves on phenotypic recovery of fast and slow muscles fibres. 1462 46

There is a strong demand for development of nerve guide conduit with prompt nerve regeneration potential for injury-induced nerve defect. Prior to study on nerve tissue engineering using Schwann cells or nerve stem cells, the effectiveness of photofabricated scaffolds based on photocurable gelatin was examined. This study describes the evaluation of in vivo nerve tissue regeneration potentials of three custom-designed and -fabricated prostheses (inner diameter, 1.2 mm; outer diameter, 2.4 mm; wall thickness, 0.60 mm; and length, 15 mm) made of photocured gelatin: a plain photocured gelatin tube (model I), a photocured gelatin tube packed with bioactive substances (laminin, fibronectin, and nerve growth factor) coimmobilized in a photocured gelatin rod (model II), and a photocured gelatin tube packed with bioactive substances coimmobilized in multifilament fibers (model III). These prostheses were implanted between the proximal and distal stumps 10 mm of the dissected right sciatic nerve of 70 adult male Lewis rats for up to 1 year. The highest regenerative potentials were found using the model III prosthesis, followed by the model II prosthesis. Markedly retarded neural regeneration was observed using the model I prosthesis. These were evaluated from the viewpoints of functional recovery, electrophysiological responses, and tissue morphological regeneration. The significance of the synergistic cooperative functions of multifilaments, which serve as a platform that provides contact guidance to direct longitudinal cell movement and tissue ingrowth and as a cell adhesive matrix with high surface area, and immobilized bioactive substances, which enhance nerve regeneration via biological stimulation, is discussed.
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PMID:Photofabricated gelatin-based nerve conduits: nerve tissue regeneration potentials. 1556 67


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