bluuebunny/crossref_metadata_2025_split huggingface dataset:
The biomechanical response to doses of TGF‐β2 in the healing rabbit medial collateral ligament
Authors: Spindler Kurt P. , Murray Martha M. , Detwiler Kenneth B. , Tarter Jeremy T. , Dawson John M. , Nanney Lillian B. , Davidson Jeffrey M. 
Published: February 2003

AbstractLigament injuries result in significant disability in over 100,000 patients each year. Despite current methods of treatment, 13% of patients with medial collateral ligament (MCL) injury develop early signs of arthritis, suggesting an incomplete return of knee stability. The principal hypothesis of this work was that the addition of TGF‐β2 to the healing MCL would accelerate the development of scar strength and stiffness. Forty‐four rabbits were divided evenly into four groups, with each group receiving either 0.1, 1 or 5 μg of TGF‐β2 and the fourth group receiving 1 μg TGF‐β2 and 1 μg of PDGF. Each rabbit underwent bilateral transection of the MCL, with one side having treatment with one of four doses of growth factor and the other side left untreated. All animals were sacrificed at 6 weeks and the structural properties of maximum load at failure, stiffness, and energy absorbed at failure measured. All treatment groups demonstrated an increase in scar mass, but no group had a significant increase in scar load at failure at 6 weeks. The addition of 0.1 μg TGF‐β2 led to a significant increase in scar stiffness. The addition of PDGF had no significant effect on any of the parameters studied. This study suggests the mechanical stiffness, but not the load at failure, of ligament scar can be significantly altered by the administration of TGF‐β2.© 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Acute changes in the axonal cytoskeleton after mild stretching of the rat brachial plexus
Authors: Kikukawa Kenshi , Fukunaga Kohji , Kato Teiji , Yamaga Makio , Miyamoto Eishichi , Takagi Katsumasa 
Published: February 2003

AbstractWe have developed an animal model to investigate acute changes in the axonal cytoskeleton caused by a mild stretching of the peripheral nerve in the upper limbs of rats. Rat forelimbs were continuously stretched at 2 N for 1 h. Thereafter, a part of the brachial plexus and median nerve were harvested and processed for electron microscopic analysis. The total number of microtubules in the brachial plexus decreased to 55% of that of the control animals (p<0.05) without change in the number of neurofilaments. No significant changes in microtubules or neurofilaments were observed in the median nerve. By Western blotting analysis, the amount of tau protein in the stretch group significantly decreased in the brachial plexus but not in the median nerve. However, no significant changes in the amount of tubulin protein were observed in either the brachial plexus or median nerve. These results suggest that the microtubules were depolymerized by stretching of the brachial plexus and that the depolymerization may have been mediated by the decrease in the tau protein.© 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Influence of a standardized closed soft tissue trauma on resistance to local infection. An experimental study in rats
Authors: Kälicke Thomas , Schlegel Urs , Printzen Gert , Schneider Erich , Muhr Gert , Arens Stephan 
Published: February 2003

AbstractPurpose: The etiology of local posttraumatic infection in the locomotor system depends on the amount, virulence and pathogenicity of the inoculated microorganisms and the local/systemic host damage due to the type and extent of the accident or iatrogenic trauma. The relative effect of these factors remains unclear. In particular, it is still unclear today whether—in presence of microorganisms—soft tissue damage and its pathophysiological consequences lead to infection after soft tissue trauma, or whether the bacterial contamination is the primarily cause for posttraumatic infection. The aim of the project was to gain information on the consequences of a soft tissue injury in terms of resistance to local infection. Since clinical populations are too heterogeneous, the problem was investigated in a standardized, reduced (no surgery or implants) experimental in vivo model.Method: In female Sprague‐Dawley‐rats with a standardized closed soft tissue trauma to the tibialis anterior muscle (group I: n = 13) or without (group II: n = 13), we compared the incidence of local infection after a pairwise local, percutaneously injected bacterial challenge with various concentrations of Staphylococcus aureus (2 × 104‐2 × 106 colony forming units, CFU). The standardized closed soft tissue trauma was created by application of a specially designed, computer controlled impact device. The contaminated soft tissue and the underlying bone were removed under sterile conditions after five days and quantitatively evaluated for bacterial growths. Infection was defined as positive bacterial growth at the soft tissue and/or bone. A stepwise experimental design with an „up‐and‐down”︁ dosage technique was used to adjust the bacterial challenge in the area of the ID50 (50% infection dose). Statistical evaluation of the difference between the infection rates of both groups was performed by two‐sided fisher exact test (p<0.05).Results: The overall infection rate was 46%. For the group with soft tissue trauma the ID50 was 1.32 × 105 CFU and 1.05 × 106 CFU for the group without soft tissue trauma. The infection rate was 69% (9 of 13 animals) for the group with soft tissue trauma and 23% (3 of 13 animals) for the group without soft tissue trauma. This difference is statistically significant (p = 0.047).Conclusions: The infection rate after a standardized closed soft tissue injury was significantly higher and the ID50 lower than without soft tissue trauma. Our results demonstrate that in presence of microorganisms it is not primarily the bacterial contamination but rather the soft tissue damage and its pathophysiological consequences resulting in decreased infection resistance that secondarily lead to infection.© 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Inhibition of tendon cell migration by dexamethasone is correlated with reduced alpha‐smooth muscle actin gene expression: A potential mechanism of delayed tendon healing
Authors: Tsai Wen‐Chung , Tang Fuk‐Tan , Wong May‐Kuen , Pang Jong‐Hwei S. 
Published: February 2003

AbstractLocal corticosteroid injection is commonly used to treat sports‐related tendon injuries. However, isolated cases of tendon rupture following injection suggest that this treatment may impair the healing process. Tendon healing requires the migration of tendon cells to the repair site, followed by the proliferation and synthesis of the extracellular matrix. This study was designed to determine the effect of dexamethasone on the migration of tendon cells intrinsic to rat Achilles tendon at concentrations similar to those typically used for local injection treatment.Furthermore, the existence of a correlation between this effect and the expression of the contractile actin isoform, α‐smooth muscle (SM) actin, which is associated with cell motility, was also examined. Using cultured tendon cells, migration was evaluated by counting the number of initial outgrowths from the tendon explants and by transwell filter migration assay. The distribution and assembly of α‐SM actin were assessed by immunocytochemistry. The mRNA and protein expressions of α‐SM actin were determined by reverse transcription‐polymerase chain reaction (RT‐PCR) and Western blot analysis. Dose‐dependent dexamethasone inhibition was demonstrated for both tendon cells outgrowth from the explants, ex vivo, and migration of tendon cells through the transwell filter, in vitro. Immunocytochemical staining revealed significant decreases in both the amount and assembly of α‐SM actin in cells.Suppression of mRNA expression and protein level of α‐SM actin was revealed from RT‐PCR and Western blot analyses. In conclusion, dexamethasone inhibits tendon cell migration that is correlated with decreased gene expression of α‐SM actin.© 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Effects of a cultured autologous chondrocyte‐seeded type II collagen scaffold on the healing of a chondral defect in a canine model
Authors: Lee C. R. , Grodzinsky A. J. , Hsu H.‐P. , Spector M. 
Published: February 2003

AbstractUsing a previously established canine model for repair of articular cartilage defects, this study evaluated the 15‐week healing of chondral defects (i.e., to the tidemark) implanted with an autologous articular chondrocyte‐seeded type II collagen scaffold that had been cultured in vitro for four weeks prior to implantation. The amount and composition of the reparative tissue were compared to results from our prior studies using the same animal model in which the following groups were analyzed: defects implanted with autologous chondrocyte‐seeded collagen scaffolds that had been cultured in vitro for approximately 12 h prior to implantation, defects implanted with autologous chondrocytes alone, and untreated defects. Chondrocytes, isolated from articular cartilage harvested from the left knee joint of six adult canines, were expanded in number in monolayer for three weeks, seeded into porous type II collagen scaffolds, cultured for an additional four weeks in vitro and then implanted into chondral defects in the trochlear groove of the right knee joints. The percentages of specific tissue types filling the defects were evaluated histomorphometrically and certain mechanical properties of the repair tissue were determined. The reparative tissue filled 88 ± 6% (mean ± SEM; range 70–100%) of the cross‐sectional area of the original defect, with hyaline cartilage accounting for 42 ± 10% (range 7–67%) of defect area. These values were greater than those reported previously for untreated defects and defects implanted with a type II collagen scaffold seeded with autologous chondrocytes within 12 h prior to implantation. Most striking, was the decreased amount of fibrous tissue filling the defects in the current study, 5 ± 5% (range 0–26%) as compared to previous treatments. Despite this improvement, indentation testing of the repair tissue formed in this study revealed that the compressive stiffness of the repair tissue was well below (20‐fold lower stiffness) that of native articular cartilage.© 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
AMPA receptor potentiation by acetylcholinesterase is age‐dependently upregulated at synaptogenesis sites of the rat brain
Authors: Olivera Silvia , Henley Jeremy M. , Rodriguez‐Ithurralde Daniel 
Published: February 2003

AbstractWe have used radioligand binding to synaptic membranes from distinct rat brain regions and quantitative autoradiography to investigate the postnatal evolution of acetylcholinesterase (AChE)‐evoked up‐regulation of α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA) receptors in CNS areas undergoing synaptogenesis. Incubation of synaptosomal membranes or brain sections with purified AChE caused a developmentally modulated enhancement in the binding of [3H]‐(S)–AMPA and the specific AMPA receptor ligand [3H]‐(S)‐5–fluorowillardiine, but did not modify binding to kainate neitherN‐methyl‐d‐aspartate receptors. In all postnatal ages investigated (4, 7, 14, 20, 27, 40 days‐old and adult rats), AChE effect on binding was concentration‐dependent and blocked by propidium, BW 284c51, diisopropylfluorophosphonate and eserine, therefore requiring indemnity of both peripheral and active sites of the enzyme. AChE‐mediated enhancement of [3H]–fluorowillardiine binding was measurable in all major CNS areas, but displayed remarkable anatomical selectivity and developmental regulation. Autoradiograph densitometry exhibited distinct temporal profiles and peaks of treated/control binding ratios for different cortices, cortical layers, and nuclei. Within the parietal, occipital and temporal neocortices, hippocampal CA1 field and cerebellum, AChE‐potentiated binding ratios peaked in chronological correspondence with synaptogenesis periods of the respective AMPA‐receptor containing targets. This modulation of AMPA receptors by AChE is a molecular mechanism able to transduce localized neural activity into durable modifications of synaptic molecular structure and function. It might also contribute to AChE‐mediated neurotoxicity, as postulated in Alzheimer's disease and other CNS disorders.
Lead‐induced developmental perturbations in hippocampal Sp1 DNA‐binding are prevented by zinc supplementation: in vivo evidence for Pb and Zn competition
Authors: Basha Md.Riyaz , Wei Wei , Brydie Michelle , Razmiafshari M. , Zawia N.H. 
Published: February 2003

AbstractZinc finger protein (ZFP) transcription factors are essential for regulation of gene expression in the developing brain. We previously reported that Pb exposure perturbed the DNA‐binding of ZFP such as Sp1 and Egr‐1 in the cerebellum, which play critical role in CNS development. In this study, we focused on hippocampal Sp1 DNA‐binding and mRNA expression in neonatal Pb‐exposed animals. The expression pattern of an Sp1 target (NMDAR1) gene was also monitored. To study in vivo and in vitro competition between Pb and Zn, we supplemented animals with Zn, and examined the effects of both metals on hippocampal Sp1 DNA‐binding and the DNA‐binding of a recombinant Sp1 protein (rhSp1). Tissue metal analysis revealed that only the disposition of Pb in the brain but not its distribution in the blood was influenced by the presence of Zn. The developmental profile of Sp1 DNA‐binding exhibited a peak on PND 15 which subsequently declined to adult levels. Consistent with earlier studies, Pb exposure produced premature peaks of Sp1 DNA‐binding on PND 5 which later returned to adult levels. The basal and Pb‐induced developmental patterns of Sp1 mRNA departed from its DNA‐binding profiles. However, the expression patterns of the NMDAR1 gene were relative to Sp1 DNA‐binding. Supplementation with zinc provided a protective effect on Pb‐induced changes in Sp1 DNA‐binding. Moreover, Pb and Zn directly interfered with the DNA‐binding of rhSp1 in vitro. These data suggest that Pb and Zn can compete both in vivo and in vitro at the zinc finger domain of Sp1 with a consequential effect on Sp1 DNA‐binding, subsequent gene expression and brain development.
Localization of urokinase‐type plasminogen activator, its receptor, and inhibitors in mouse forebrain during postnatal development
Authors: Del Bigio Marc R. , Hosain Shahid , Altumbabic Mensura 
Published: February 2003

AbstractProteolytic enzymes are postulated to play a role in cell migration and synapse organization during brain development. Among these, urokinase‐type plasminogen activator (uPA) has been studied in neoplastic and cultured brain cells extensively. We hypothesized that uPA, its receptor, and its inhibitors would be expressed in immature glial and neuronal cells in postnatal mouse forebrain. Immature cortical neurons were immunoreactive for uPA, its receptor, and its substrate plasminogen peaking at the end of postnatal week two, consistent with the postulated role in synaptogenesis. Immunoreactivity for uPA receptor was also observed on astroglial cells in vitro. Neither it nor uPA were convincingly detected in subventricular zone precursor cells, immature white matter or pre‐labeled immature cells that had been transplanted into brain. Plasminogen activator inhibitor type 1 immunoreactivity was observed on endothelia up to 12 days age, and type 2 was observed to surround immature cells.We conclude, based on the spatial and temporal distribution of immunoreactivity, that uPA and its receptor may be relatively more important for synaptogenesis, remodeling, and reactive processes than for cell migration in developing mouse brain.
Repeated seizure‐associated long‐lasting changes of N‐methyl‐d‐aspartate receptor properties in the developing rat brain
Authors: Doriat Jean‐François , Koziel Violette , Humbert Anne‐Claude , Daval Jean‐Luc 
Published: February 2003

AbstractGlutamate NMDA receptor has been implicated in brain developmental processes as well as in excitotoxicity and seizure mediation. A previous study has shown that an acute episode of seizures for 30 min in rats altered NMDA receptor characteristics, mainly in the very immature animal. In order to assess whether receptor modifications may also account for long‐lasting cerebral disabilities, medium‐ and long‐term consequences of repeated seizures in developing rats on brain NMDA receptor properties were investigated. Seizures were induced once a day for 3 consecutive days, either from postnatal day 5 (P5) to P7 or from P15 to P17. NMDA receptors were then analysed at P15, P25 and P60 (adulthood) by measuring specific binding of [3H]MK‐801 on brain membrane preparations. In addition, allosteric modulation of NMDA receptors by exogenous glutamate and glycine was investigated. Seizures from P5 to P7 led to a 22% increase in the density of [3H]MK‐801 binding sites measured at P15, but did not affect NMDA receptor density or affinity at P25 or P60. P15–P17 seizures led to a 21% decrease in the density of binding sites and to a 33% decrease in receptor dissociation constant at P25, while they were without effect at P60. Moreover, P5–P7 and P15–P17 seizures were both associated with a suppression of the glutamate/glycine‐induced receptor activation at P60. These modifications might account for long‐term alterations in cerebral excitability or plasticity after early convulsive disorders, with regards to altered cognitive capacities, epileptogenesis and brain susceptibility to recurrent seizures.
Fluoride‐induced depletion of polyphosphoinositides in rat brain cortical slices: a rationale for the inhibitory effects on phospholipase C
Authors: Sarri Elisabet , Claro Enrique 
Published: February 2003

AbstractFluoride, which is used commonly as a pharmacological tool to activate phosphoinositide‐phospholipase C coupled to the heterotrymeric Gq/11 proteins, inhibited the phosphorylation of phosphatidylinositol (PtdIns) to polyphosphoinositides (PtdIns4P and PtdIns4,5P2) in membranes from rat brain cortex. Fluoride enhanced basal production of 3H‐inositol phosphates in membranes prepared from brain cortical slices that had been prelabeled with [3H]inositol, but inhibited the stimulation elicited by carbachol in the presence of GTPγS. However in both cases fluoride depleted [3H]PtdIns4P content by 95%. The inhibitory effects of fluoride on the release of 3H‐inositol phosphates in slices were not apparent in a pulse [3H]inositol‐labeling strategy, but became dramatic in a continuous labeling protocol, particularly at long incubation times. Prelabeling slices with [3H]inositol in the presence of fluoride precluded polyphosphoinositide labeling, and eliminated phospholipase C responsiveness to carbachol under normal or depolarizing conditions, and to the calcium ionophore ionomycin. The lack of response of 3H‐polyphosphoinositide‐depleted slices to phospholipase C stimuli was not due to fluoride poisoning, unaccesibility of the [3H]inositol label to phospholipase C or desensitization of Gq/11, as the effect of carbachol and GTPγS was restored, in the presence of ATP, in membranes prepared from slices that had been labeled in the presence of fluoride. In conclusion, our data show that fluoride, at a concentration similar to that used to stimulate directly Gq/11‐coupled phospholipase C, effectively blocks the synthesis of phospholipase C substrates from PtdIns.
Cellular localization of estrogen receptors on neurones in various regions of cultured rat CNS: coexistence with cholinergic and galanin receptors
Authors: Hösli Elisabeth , Hösli L. 
Published: February 2003

AbstractAutoradiographic studies have shown that many neurones in explant cultures of rat neocortex, hippocampus, preoptic area and spinal cord express binding sites for [3H]‐estradiol which are distributed over the cell bodies and primary processes. By means of immunohistochemistry, it was observed that neurones were labelled by monoclonal antibodies against estrogen α‐receptors and a polyclonal antibody against estrogen β‐receptors. Immunoreactivity was distributed over the soma and primary processes of the cells, the nuclei being more intensely stained. Double‐immunostaining revealed a colocalization of estrogen α‐ and β‐receptors on approximately half of the neurones in cultures from neocortex and hippocampus whereas in cultures from preoptic area and spinal cord only few cells were double‐stained. On many neurones, a coexistence of estrogen receptors and cholinergic muscarinic or nicotinic sites was found. Furthermore, combined autoradiographic and immunohistochemical studies have shown a colocalization of receptors for estrogen and the neuropeptide [125I]‐galanin. The coexistence of estrogen and cholinergic sites as well as of estrogen and galanin receptors on the same neurones are discussed with respect to neurodegenerative events such as Alzheimer's disease.
Plasticity of 5‐hydroxytryptamine1B receptors during postnatal development in the rat visual cortex
Authors: Ruiz Gloria , Bancila Mircea , Valenzuela Mauricio , Daval Geneviève , Hossein Kia Kami , Vergé Daniel 
Published: February 2003

AbstractThe distribution of 5‐hydroxytryptamine1A and 5‐hydroxytryptamine1B receptors in the visual cortex was studied by quantitative autoradiography during postnatal development. Overall, receptor densities increased throughout development, but exhibited regional rearrangements, particularly in the case of 5‐hydroxytryptamine1B receptors. Neonatal treatment with 5,7‐dihydroxytryptamine, which causes selective degeneration of serotoninergic neurons, had no effect on the density of 5‐hydroxytryptamine1A receptors in the visual cortex. However, a transient increase in 5‐hydroxytryptamine1B at postnatal days 10–12 was observed after this treatment, suggesting a regulation of postsynaptic receptors. Neonatal enucleation resulted in a marked increase in 5‐hydroxytryptamine1B binding sites in all layers of the visual cortex by P16, whereas it had no effect upon 5‐hydroxytryptamine1A binding sites.These results show that both receptor subtypes do not exhibit striking transient features in the visual cortex during postnatal development, but rather undergo discrete reorganizations. 5‐Hydroxytryptamine1B receptors show changes in density after either neonatal degeneration of serotoninergic neurons or enucleation, indicating that the serotoninergic system involving this receptor subtype can exhibit some postnatal plasticity in the visual cortex.