bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microglial dystrophy in the aged and Alzheimer's disease brain is associated with ferritin immunoreactivity
Authors: Lopes Kryslaine O. , Sparks D. Larry , Streit Wolfgang J. 
Published: April 2008

AbstractDegeneration of microglial cells may be important for understanding the pathogenesis of aging‐related neurodegeneration and neurodegenerative diseases. In this study, we analyzed the morphological characteristics of microglial cells in the nondemented and Alzheimer's disease (AD) human brain using ferritin immunohistochemistry. The central hypothesis was that expression of the iron storage protein ferritin increases the susceptibility of microglia to degeneration, particularly in the aged brain since senescent microglia might become less efficient in maintaining iron homeostasis and free iron can promote oxidative damage. In a primary set of 24 subjects (age range 34–97 years) examined, microglial cells immunoreactive for ferritin were found to constitute a subpopulation of the larger microglial pool labeled with an antibody for HLA‐DR antigens. The majority of these ferritin‐positive microglia exhibited aberrant morphological (dystrophic) changes in the aged and particularly in the AD brain. No spatial correlation was found between ferritin‐positive dystrophic microglia and senile plaques in AD tissues. Analysis of a secondary set of human postmortem brain tissues with a wide range of postmortem intervals (PMI, average 10.94 ± 5.69 h) showed that the occurrence of microglial dystrophy was independent of PMI and consequently not a product of tissue autolysis. Collectively, these results suggest that microglial involvement in iron storage and metabolism contributes to their degeneration, possibly through increased exposure of the cells to oxidative stress. We conclude that ferritin immunohistochemistry may be a useful method for detecting degenerating microglia in the human brain. © 2008 Wiley‐Liss, Inc.
The chemokine receptor CXCR2 is differentially regulated on glial cells in vivo but is not required for successful remyelination after cuprizone‐induced demyelination
Authors: Lindner Maren , Trebst Corinna , Heine Sandra , Skripuletz Thomas , Koutsoudaki Paraskevi N. , Stangel Martin 
Published: April 2008

AbstractUnravelling the factors that can positively influence remyelination is one of the major challenges in multiple sclerosis research. Expression of the chemokine receptor CXCR2 on oligodendrocytes both in vitro and in MS lesions has suggested a possible role for CXCR2 in the recruitment of oligodendrocyte precursor cells (OPC). To investigate the function of CXCR2 during remyelination in vivo, we studied this receptor in cuprizone‐induced demyelination and subsequent remyelination. We found that CXCR2 is constitutively expressed on OPC, whereas on macrophages/microglia CXCR2 is upregulated upon activation during demyelination. Hence, the expression of CXCR2 is differentially regulated in oligodendrocytes and macrophages/microglia. Furthermore, we subjected CXCR2−/− mice to the cuprizone model demonstrating that remyelination was not altered in comparison to wildtype controls. In addition, the number of OPC and the amount of microglial accumulation were similar in both CXCR2−/− and wildtype animals during the whole demyelination and remyelination process. These results suggest that despite expression on OPC and microglia CXCR2 plays only a minor role during remyelination. © 2008 Wiley‐Liss, Inc.
Activated microglia modulate astroglial enzymes involved in oxidative and inflammatory stress and increase the resistance of astrocytes to oxidative stress in Vitro
Authors: Röhl Claudia , Armbrust Elisabeth , Kolbe Karola , Lucius Ralph , Maser Edmund , Venz Simone , Gülden Michael 
Published: April 2008

AbstractNeuropathological processes in the central nervous system are commonly accompanied by an activation of microglia and astrocytes. The involvement of both cell populations in the onset and progress of neurological disorders has been widely documented, implicating both beneficial and detrimental influences on the neural tissue. Nevertheless, little is known about the interplay of these glial cell populations, especially under diseased conditions. To examine the effects of activated microglia on astrocytes purified rat astroglial cell cultures were treated with medium conditioned by purified quiescent (MCM[−]) or lipopolysaccharide (LPS)‐activated rat microglia (MCM[+]) and subjected to a comparative proteome analysis based on two‐dimensional gel electrophoresis. No significant down regulation of proteins was observed. The majority of the 19 proteins identified by means of nano HPLC/ESI‐MS/MS in the 12 most prominent protein spots significantly overexpressed (≥2‐fold) in MCM[+] treated astrocytes are involved in inflammatory processes and oxidative stress response: superoxide dismutases (Sod), peroxiredoxins, glutathione S‐transferases (Gst), nucleoside diphosphate kinase B, argininosuccinate synthase (Ass), and cellular retinol‐binding protein I (Rbp1). Sod2, Rbp1, Gstp1, and Ass were also significantly increased on the mRNA level determined by quantitative RT‐PCR. The upregulation of antioxidative enzymes in astrocytes was accompanied by a higher resistance to oxidative stress induced by H2O2. These results show that activated microglia change the expression of antioxidative proteins in astrocytes and protect them against oxidative stress, which might be an effective way to increase the neuroprotective potential of astrocytes under pathological conditions associated with oxidative stress and inflammation. © 2008 Wiley‐Liss, Inc.
Sodium signals in cerebellar Purkinje neurons and Bergmann glial cells evoked by glutamatergic synaptic transmission
Authors: Bennay Mustapha , Langer Julia , Meier Silke D. , Kafitz Karl W. , Rose Christine R. 
Published: April 2008

AbstractGlial cells express specific high‐affinity transporters for glutamate that play a central role in glutamate clearance at excitatory synapses in the brain. These transporters are electrogenic and are mainly energized by the electrochemical gradient for sodium. In the present study, we combined somatic whole‐cell patch‐clamp recordings with quantitative Na+ imaging in fine cellular branches of cerebellar Bergmann glial cells and in dendrites of Purkinje neurons to analyze intracellular Na+ signals close to activated synapses. We demonstrate that pressure application of glutamate and glutamate agonists causes local Na+ signals in the mM range. Furthermore, we analyzed the pharmacological profile, as well as the time course and spatial distribution of Na+ signals following short synaptic burst stimulation of parallel or climbing fibers. While parallel fibers stimulation resulted in local sodium transients that were largest in processes close to the stimulation pipette, climbing fibers stimulation elicited global sodium transients throughout the entire cell. Glial sodium signals amounted to several mM, were mainly caused by sodium influx following inward transport of glutamate and persisted for tens of seconds. Sodium transients in dendrites of Purkinje neurons, in contrast, were mainly caused by activation of AMPA receptors and had much faster kinetics. By reducing the driving force for sodium‐dependent glutamate uptake, intracellular sodium accumulation in glial cells upon repetitive activity might provide a negative feedback mechanism, promoting the diffusion of glutamate and the activation of extrasynaptic glutamate receptors at active synapses in the cerebellum. © 2008 Wiley‐Liss, Inc.
Inhibition of Rho‐dependent pathways by Clostridium botulinum C3 protein induces a proinflammatory profile in microglia
Authors: Hoffmann Anja , Hofmann Fred , Just Ingo , Lehnardt Seija , Hanisch Uwe‐Karsten , Brück Wolfgang , Kettenmann Helmut , Ahnert‐Hilger Gudrun , Höltje Markus 
Published: April 2008

AbstractSuccessful regeneration in the central nervous system crucially depends on the adequate environment. Microglia as brain immune‐competent cells importantly contribute to this task by producing pro‐ and anti‐inflammatory mediators. Any environmental change transforms these cells towards an activated phenotype, leading to major morphological, transcriptional and functional alterations. Rho GTPases affect multiple cellular properties, including the cytoskeleton, and C3 proteins are widely used to study their involvement. Especially C3bot from Clostridium botulinum has been considered to promote neuronal regeneration by changing Rho activity. Yet C3bot may exert cellular influences through alternative mechanisms. To determine the role of Rho‐dependent pathways in microglia we investigated the influence of C3bot on functional properties of cultivated primary mouse microglial cells. Nanomolar concentrations of C3bot transformed microglia towards an activated phenotype and triggered the release of nitric oxide and several proinflammatory cyto‐ and chemokines. These inductions were not mediated by the ROCK‐kinase pathway, since its selective inhibitors Y27632 and H1152 had no effect. C3‐induced and Rho‐mediated NO release was instead found to be under the control of NFκB, as revealed by treatment with the NFκB inhibitor PDTC. Thus, C3bot induces a proinflammatory response in microglia resembling the classical proinflammatory phenotype elicited by bacterial LPS. The findings are relevant for the use of C3bot in regenerative approaches. © 2008 Wiley‐Liss, Inc.
Prognostic impact of bcl‐2 expression on advanced nasopharyngeal carcinoma
Authors: Chen Mu‐Kuan , Lai Jui‐Chung , Chang Cheng‐Chuan , Chang Julia H. , Chang Yu‐Jun , Chen Hui‐Chuan 
Published: April 2008

AbstractBackgroundOur aim was to evaluate the prognostic impact of bcl‐2 expression on patients with advanced nasopharyngeal carcinoma (NPC).MethodsOne hundred five patients with advanced NPC treated with high‐dose radiotherapy were included. The relationship between bcl‐2 expression, TNM stage, and disease‐specific survival was analyzed.ResultsWithin the same stage III and IV, patients with negative bcl‐2 expression had better disease‐free survival. The disease‐free survival of patients with stage IV NPC with negative bcl‐2 expression was paradoxically better than that of patients with stage III NPC with positive bcl‐2 expression. In the advanced NPC, the disease‐free survival of patients with stage III cancer was better than that of patients with stage IV cancer (p = .06); in contrast, patients with bcl‐2‐positive tumors had a worse disease‐free 5‐year survival (p = .02). The Cox regression model revealed that only bcl‐2 expression was statistically significant (p = .03).ConclusionIn advanced staged NPC, bcl‐2 expression represented an important prognostic factor. © 2008 Wiley Periodicals, Inc. Head Neck, 2008
Using multiple‐variable indicator kriging to assess groundwater quality for irrigation in the aquifers of the Choushui River alluvial fan
Authors: Jang Cheng‐Shin , Chen Shih‐Kai , Ching‐Chieh Lin 
Published: April 2008

AbstractThis work attempted to locate clean and safe groundwater for irrigation use in the Choushui River alluvial fan. Multiple‐variable indicator kriging (MVIK) was adopted to evaluate numerous hydrochemical parameters for a standard of water quality for irrigation in Taiwan. Many hydrochemical parameters in groundwater were distinguished into three main categories—salinity/sodium hazard, nitrogen hazard and heavy metal hazard. Safe and potential hazardous regions of groundwater for irrigation were delineated according to different probabilities estimated by MVIK. The probabilistic results of the classifications gave an opportunity to explore the spatial uncertainty of the hazards and helped government administrators establish a sound policy associated with the development and management of groundwater resources. Analysis of the results indicate that the central distal‐fan and mid‐fan aquifers are the best places to extract clean and safe groundwater for irrigation, and the deep aquifer (exceeding 200 m depth) has wider regions with clean and safe groundwater for irrigation than shallow aquifers. The northern and southern aquifers, with multiple hazards, limit groundwater use for irrigation. Although the proximal‐fan aquifer is a zone of groundwater recharge, the high nitrogen content seriously affects the environment and is not suitable for irrigation use. Copyright © 2008 John Wiley & Sons, Ltd.
The mechanical strength of collagen gels containing glycosaminoglycans and populated with fibroblasts
Authors: Saddiq Ziad A. , Barbenel Joseph C. , Grant M. Helen 
Published: April 2008

AbstractCollagen gels provide a biocompatible matrix for replacing soft tissues, but it is essential to determine whether the mechanical properties of the matrix can be retained after cell ingrowth into the collagen scaffold. We have determined the mechanical strength of four collagen gel compositions (plain collagen; collagen‐chrondroitin‐6‐sulphate glycosaminoglycan (GAG); collagen crosslinked with carbodiimide and putrescine, and collagen‐GAG with the crosslinkers) in the presence of either 3T3 mouse fibroblasts or human skin fibroblasts, to determine whether cellular activity influences the mechanical properties of the matrix, and whether the crosslinking processes alter the effects of the cells. The presence of GAG and the crosslinkers increased the strength and stiffness of the unseeded gels, but there was no evidence for synergy between these treatments. In all cases, the gels became significantly weaker after 6 days in the presence of either human or mouse fibroblasts, as judged by the decrease in the values of the maximum load and stress before failure, and the stiffness decreased as shown by the lower values of the incremental modulus. With most parameters, the effect of the cells was independent of gel composition, and the presence of crosslinkers or GAG did not impart resistance to the cell‐induced decrease in strength. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Selective protein adsorption modulates platelet adhesion and activation to oligo(ethylene glycol)‐terminated self‐assembled monolayers with C18 ligands
Authors: Gonçalves Inês C. , Martins M. Cristina L. , Barbosa Mário A. , Naeemi Esmaeel , Ratner Buddy D. 
Published: April 2008

AbstractThis study focuses on the selective binding of albumin to a nanostructured surfaces to inhibit other blood proteins from adsorbing thereby reducing platelet adhesion and activation. Tetra (ethylene‐glycol)‐terminated self‐assembled monolayers (EG4 SAMs) with different percentages of C18 ligands on the surface were characterized by contact angle measurements, X‐ray photoelectron microscopy, infrared reflection‐absorption spectroscopy, and ellipsometry. A specific surface (2.5% C18 SAM) was found to be selective for human serum albumin (HSA) in the presence of both albumin and fibrinogen (HFG). The importance of this concentration of C18 ligands was stressed in reversibility studies since that surface exchanged almost all the preadsorbed HSA by HSA in solution, but not by HFG. The effect of protein adsorption in the subsequent adhesion and activation of platelets was studied by pre‐immersing the surfaces in albumin and plasma before contact with platelets. Scanning electron microscopy and glutaraldehyde induced fluorescence technique images showed that as surfaces got more hydrophobic due to the immobilization of C18 ligands, the number of adherent platelets increased and their morphology changed from round to fully spread. Pre‐immersion in HSA led to an 80% decrease in platelet adhesion and reduction of activation. Pre‐immersion in 1% plasma was only relevant in 2.5% C18 SAMs since this was the only surface that demonstrated less adhesion of platelets comparing with buffer pre‐immersion. However, they still adsorb more platelets then when HSA was preadsorbed. This was confirmed in competition studies between HSA and plasma that suggested that other plasma proteins were also adsorbing to this surface. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Mineral apposition rates provide significant information on long‐term effects in BMP‐induced bone regeneration
Authors: Schopper Christian , Moser Doris , Spassova‐Tzekova Else , Russmueller Guenter , Goriwoda Walter , Lagogiannis Georgios , Ewers Rolf , Redl Heinz 
Published: April 2008

AbstractIn this study, a CaP biomaterial was used as a carrier for rhBMP‐2. Biomaterials were investigated in calvarial and femoral defects using a rabbit animal model, with unloaded biomaterials serving as control. Fluorochrome labels were administered at days 14 and 70. Specimens were retrieved after 12 weeks for histological analysis. When area fractions were assessed by conventional histomorphometry, no significant effect of rhBMP‐2 on the amounts of regenerated bone and residual biomaterial were seen by 12 weeks. After mineral appositional rate (MAR) measurement using double labels, calculation yielded significantly higher MARs for defects at both implantation sites, when compared with surrounding bone, whether or not biomaterials were loaded with rhBMP‐2. Analyzing the effect of rhBMP‐2, both defect sites showed significantly higher MARs in the rhBMP‐2 group. MARs of bone surrounding the defects had also been elevated significantly by rhBMP‐2 at calvarial and femoral implantation sites. It is concluded that MAR measurement is suitable to identify long‐term effects of rhBMP‐2 on bone formation at a time when conventional histomorphometry using fractional area determination is inadequate. Also, by MAR assessment, effects of rhBMP‐2 on surrounding bone can be documented. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Gentamicin‐eluting bioresorbable composite fibers for wound healing applications
Authors: Zilberman Meital , Golerkansky Esty , Elsner Jonathan J. , Berdicevsky Israela 
Published: April 2008

AbstractNew gentamicin‐eluting bioresorbable core/shell fiber structures were developed and studied. These structures were composed of a polyglyconate core and a porous poly(DL‐lactic‐co‐glycolic acid) (PDLGA) shell loaded with the antibiotic agent gentamicin, prepared using freeze drying of inverted emulsions. These unique fibers are designed to be used as basic elements of bioresorbable burn and ulcer dressings. The investigation focused on the effects of the emulsion's composition (formulation) on the shell's microstructure, on the drug release profile from the fibers, and on bacterial inhibition. The release profiles generally exhibited an initial burst effect accompanied by a decrease in release rates with time. Albumin was found to be the most effective surfactant for stabilizing the inverted emulsions. All three formulation parameters had a significant effect on gentamicin's release profile. An increase in the polymer and organic:aqueous phase ratio or a decrease in the drug content resulted in a lower burst release and a more moderate release profile. The released gentamicin also resulted in a significant decrease in bacterial viability and practically no bacteria survived after 2 days when using bacterial concentrations of 1 × 107 CFU/mL. Thus, our new fiber structures are effective against the relevant bacterial strains and can be used as basic elements of bioresorbable drug‐eluting wound dressings. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Microfabricated poly(ethylene glycol) templates enable rapid screening of triculture conditions for cardiac tissue engineering
Authors: Iyer Rohin K. , Chiu Loraine L. Y. , Radisic Milica 
Published: April 2008

AbstractThe purpose of this study was to design a simple system for cultivation of micro‐scale cardiac organoids and investigate the effects of cellular composition on the organoid function. We hypothesized that cultivation of cardiomyocytes (CM) on preformed networks of fibroblasts (FB) and endothelial cells (EC) would enhance the structural and functional properties of the organoids, compared to simultaneously seeding the three cell types or cultivating enriched CM alone. Microchannels for cell seeding were created by photopolymerization of poly(ethylene glycol) diacrylate. In the preculture group the channels were seeded with a mixture of NIH 3T3 FB and D4T EC, following by addition of neonatal rat CM after 2 days of FB/EC preculture. The control microchannels were seeded simultaneously with FB/EC/CM (simultaneous triculture) or with enriched CM alone (enriched CM). Preculture resulted in cylindrical, contractile, and compact cardiac organoids that contained elongated CM expressing connexin‐43 and cardiac troponin I. In contrast, simultaneous triculture resulted in noncontractile organoids with clusters of CM growing separately from elongated FBs and ECs. The staining for Connexin‐43 was absent in the simultaneous triculture group. When fixed or frozen FB/EC were utilized as a preculture substrate for CM, noncontractile organoids were obtained; while preculture on a single cell type (either FB or EC) resulted in contractile organoids but with inferior properties compared to preculture with both FB/EC. These results emphasize the importance of living cells, presence of both nonmyocyte cell types as well as sequential seeding approach for cultivation of functional multicell type cardiac organoids. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Comparative effects of scaffold pore size, pore volume, and total void volume on cranial bone healing patterns using microsphere‐based scaffolds
Authors: Petrie Aronin Caren E. , Sadik Karim W. , Lay Ann L. , Rion Dave B. , Tholpady Sunil S. , Ogle Roy C. , Botchwey Edward A. 
Published: April 2008

AbstractBony craniofacial deficits resulting from injury, disease, or birth defects remain a considerable clinical challenge. In this study, microsphere‐based scaffold fabrication methods were use to study the respective effects of scaffold pore size, open pore volume, and total void volume fraction on osseous tissue infiltration and bone regeneration in a critical size rat cranial defect. To compare the healing effects of these parameters, three different scaffolds types were fabricated: solid 100 μm spheres, solid 500 μm spheres, and hollow 500 μm spheres. These constructs were implanted into surgically created rat calvarial defects. By 90‐days post op, results of micro computed tomography (CT) analysis showed that all scaffolds generated similar amounts of new bone which was significantly greater than untreated controls. Interestingly, the spatial distribution of new bone within the defect area varied by scaffold group. MicroCT and histological analysis demonstrated healing restricted to the dural side in the hollow 500 μm group, whereas the solid 500 μm group demonstrated healing along the dural side and within the center of the defect. Solid 100 μm groups demonstrated healing along the dural layer, periosteal layer, and within the center of the defect. These results suggest that pore size and closed void volume may both play important roles in scaffold degradation patterns and associated bone healing. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009