bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential regulation of VEGF, HIF1α and angiopoietin‐1, ‐2 and ‐4 by hypoxia and ionizing radiation in human glioblastoma
Authors: Lund Eva L. , Høg Anja , Olsen Minna W.B. , Hansen Lasse T. , Engelholm Svend A. , Kristjansen Paul E.G.
Published: January 2004

We examined how ionizing radiation (IR) delivered under either severe hypoxia (< 0.1% O2) or normoxia affects the expression of hypoxia inducible factor 1α (HIF‐1α) and the angiogenic factors vascular endothelial growth factor (VEGF) and angiopoietins 1, 2 and 4 in U87 human glioblastoma cells. IR was delivered as single doses of 0, 2, 5, 10 and 20 Gy after 6‐hr hypoxic incubation and in normoxic controls. Irradiation at any dose did not affect the cellular protein levels of any of the angiopoietins, whereas hypoxia led to increasing levels of both angiopoietin‐4 and angiopoietin‐2. Levels of angiopoietin‐1 protein were unaltered throughout the observation period. A dose‐dependent increase in levels of secreted VEGF in the medium occurred after IR at doses from 5–20 Gy. In hypoxic cells, 20 Gy IR induced an additional significant increase in VEGF relative to nonirradiated hypoxic control cells with elevated baseline VEGF levels induced by hypoxia. HIF‐1α and glucose transporter‐1 (Glut‐1) were not correspondingly upregulated by IR. Blocking HIF‐1α by antisense treatment induced a reduced baseline VEGF at normoxia, while the relative upregulation of VEGF by IR was unaffected. These data provide evidence that VEGF is upregulated by IR by mechanisms independent of HIF‐1 transactivation. © 2003 Wiley‐Liss, Inc.
Effects of adrenomedullin on endothelial cells in the multistep process of angiogenesis: Involvement of CRLR/RAMP2 and CRLR/RAMP3 receptors
Authors: Fernandez‐Sauze Samantha , Delfino Christine , Mabrouk Kamel , Dussert Christophe , Chinot Olivier , Martin Pierre‐Marie , Grisoli Francois , Ouafik L'Houcine , Boudouresque Françoise
Published: January 2004

Recently, we demonstrated that U87 glioblastoma xenograft tumors treated with anti‐adrenomedullin (AM) antibody were less vascularized than control tumors, suggesting that AM might be involved in neovascularization and/or vessel stabilization. Angiogenesis, the sprouting of new capillaries from preexisting blood vessels, is a multistep process that involves migration and proliferation of endothelial cells, remodeling of the extracellular matrix and functional maturation of the newly assembled vessels. In our study, we analyzed the role of AM on human umbilical vein endothelial cell (HUVEC) phenotype related to different stages of angiogenesis. Here we report evidence that AM promoted HUVEC migration and invasion in a dose‐dependent manner. The action of AM is specific and is mediated by the calcitonin receptor‐like receptor/receptor activity‐modifying protein‐2 and ‐3 (CRLR/RAMP2; CRLR/RAMP3) receptors. Furthermore, AM was able to induce HUVEC differentiation into cord‐like structures on Matrigel. Suboptimal concentrations of vascular endothelial growth factor (VEGF) and AM acted synergistically to induce angiogenic‐related effects on endothelial cells in vitro. Blocking antibodies to VEGF did not significantly inhibit AM‐induced capillary tube formation by human endothelial cells, indicating that AM does not function indirectly through upregulation of VEGF. These findings suggest that the proangiogenic action of AM on cultured endothelial cells via CRLR/RAMP2 and CRLR/RAMP3 receptors may translate in vivo into enhanced neovascularization and therefore identify AM and its receptors acting as potential new targets for antiangiogenic therapies. © 2003 Wiley‐Liss, Inc.
Maternal representations during pregnancy and early motherhood
Authors: Ilicali Ebru Taskin , Fisek Guler Okman
Published: January 2004

The aim of the present study was to study the maternal representations of pregnant women and mothers in their early postpartum period, by beginning the process of validating the maternal representations questionnaire L'entretien R1 and by developing a means to assess the content‐free aspects of the representations. Participants were 23 primiparous (first‐time mothers) pregnant women in their fourth to seventh month of pregnancy and 22 primiparous mothers in their early (zero to six months) postpartum period. It was found that the four subscales of L'entretien (self‐as‐mother, self‐as‐person, own‐mother, and partner) produced meaningful results for Turkish subjects. The results were compatible with the idea of integrated representations of self‐as‐person and self‐as‐mother even in the second trimester of their pregnancy and also showed that they could differentiate themselves from their mothers as early as that period. The results revealed no significant differences in the content and content‐free dimensions of the representations of pregnant women and mothers. ©2004 Michigan Association for Infant Mental Health.
Maternal limit setting during toddlerhood, delay of gratification, and behavior problems at age five
Authors: Houck Gail M. , Lecuyer‐Maus Elizabeth A.
Published: January 2004

In this study, self‐regulation was examined in relation to maternal limit setting during toddlerhood. Observational coding of limit‐setting interactions was carried out at 12, 24, and 36 months using the Prohibition Coding Scheme (Houck & LeCuyer, 1995; LeCuyer‐Maus & Houck, 2002). At five years, self‐regulation was assessed by observation of self‐imposed delay‐of‐gratification (Shoda, Mischel, & Peake, 1990), and behavior problems were measured by maternal report on a behavior checklist (CBCL; Achenbach, 1991). Maternal limit‐setting patterns at every age differentiated subsequent duration of delay, but not behavior problems. A power‐based maternal pattern in limit setting adversely affected later self‐imposed delay. Although an indirect limit‐setting pattern optimized the child's delay duration, a teaching‐based pattern yielded more consistently positive outcomes at 36 months and normative delay durations at age five years. ©2004 Michigan Association for Infant Mental Health.
Parent‐completed screening for social emotional problems in young children: The effects of risk/disability status and gender on performance
Authors: Squires Jane , Bricker Diane , Twombly Elizabeth
Published: January 2004

Results of psychometric studies on the Ages and Stages Questionnaires: Social Emotional (ASQ:SE), a parent‐completed screening tool for infants, toddlers, and preschoolers, are described. The ability of the ASQ:SE to distinguish risk and disabilities groups, and the relationship of gender and ASQ:SE scores were examined. No/low risk, at risk, developmental disabilities, and social emotional disability groups were significantly different at all eight age intervals (i.e., 6, 12, 18, 24, 30, 36, 48, and 60 months). Significant differences were found between males and females at the 30‐, 36‐, 48‐, and 60‐month age intervals. These data support the ASQ:SE as a valid screening test to assist in early identification of social and emotional problems in young children. ©2004 Michigan Association for Infant Mental Health.
Predicting maternal reactivity/sensitivity: The role of infant emotionality, maternal depressiveness/anxiety, and social support
Authors: Mertesacker Bettina , Bade Ulla , Haverkock Antje , Pauli‐Pott Ursula
Published: January 2004

It was hypothesized that an accumulation of unfavorable conditions, i.e., high negative emotionality and low positive emotionality of the infant, maternal depression and anxiety, and lacking social and emotional support can attenuate mothers' reactivity/sensitivity. Maternal reactivity/sensitivity was observed during home visits and in the laboratory. Infant negative and positive emotionality was assessed by mother reports and behavioral observations. Maternal depressiveness/anxiety as well as social support were assessed via questionnaires. All mothers were primiparous and had healthy infants. Data collection was conducted at the infants' ages of four months (37 dyads) and eight months (33 dyads). The sample consisted of 19 male and 18 female infants (four‐months' measurement). Whereas the presence of a single risk factor was not related to maternal reactivity/sensitivity, the combination was. A decrease in maternal reactivity/sensitivity over the course of time was demonstrated for mothers who had to deal with high negative emotionality of the infant in combination with either high depressiveness/anxiety or low social support at the infants' age of four months. No significant main or interaction effects could be shown for infant positive emotionality. ©2004 Michigan Association for Infant Mental Health.
First‐time mothers in home visitation services utilizing child development specialists
Authors: Culp Anne McDonald , Culp Rex E. , Hechtner‐Galvin Tamara , Howell Christina S. , Saathoff‐Wells Tara , Marr Pam
Published: January 2004

Professionals in the field of child development were employed to provide home visitation services to 156 mothers and infants prenatally through the infants' first birthdays. Compared to a control group of mothers (n = 107), the intervention mothers utilized more community resources, had safer homes, had more appropriate developmental expectations, had better understanding of noncorporal punishment, and had behaviors that were more accepting and respectful to their infants. The home visitors were well educated, with experience in home visitation, and supervised. Program implementation procedures were documented and supervised. Program fidelity and the efficacy of using child development specialists as home visitors are discussed in regards to the positive findings. ©2004 Michigan Association for Infant Mental Health.
Effect of composition of interpenetrating polymer network hydrogels based on poly(acrylic acid) and gelatin on tissue response: A quantitative in vivo study
Authors: Burugapalli Krishna , Koul Veena , Dinda Amit K.
Published: December 2003

The local tissue response of the biomaterial is the most important criteria for determination of its biocompatibility. In the present study, full and semi‐interpenetrating polymer networks (IPN) based on polyacrylic acid (AAc) and gelatin (Ge) crosslinked with 0.5 mol % N,N′‐methylene bisacrylamide (BAm) and 4% glutaraldehyde (GA), respectively, were evaluated for tissue response in rats. IPNs with varying ratios of AAc and Ge were implanted subcutaneously in rats. Gentamicin sulfate (GS)‐loaded IPN samples were also studied to evaluate the possible therapeutic use of these polymers. The site of implantation was biopsied and processed for light microscopy (LM) with image analysis for assessment of tissue reaction at 2‐, 6‐, and 12‐week intervals. The tissue reaction was evaluated as a function of composition and time. The degree of neutrophil, lymphocyte and macrophage infiltration, fibrosis, granuloma formation, integration with extracellular matrix, vascular proliferation, and damage of adjacent structures were assessed. Polymers with >66% crosslinked Ge (Gx) showed persistence of acute inflammatory reaction till 3 months, with marked tissue injury and fibrosis. On the other hand, high crosslinked AAc (Ax) content showed chronic inflammatory reaction with high macrophage infiltration. Macrophages took active part in phagocytosis, degradation, and removal of polymers without granuloma formation or significant giant cell reaction. The IPNs with acrylic acid and gelatin in the ratio of 1:1 showed least tissue reaction and thus appeared to be most biocompatible. The majority of the polymers showed integration with extracellular matrix and growth of capillaries in and around the polymer. The heamogram, liver and renal function tests, and histology of vital organs were all normal. GS loading showed no additional local or systemic reaction suggesting the potential usefulness of the hydrogels as carrier for drugs such as GS. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 68A: 210–218, 2004
Carboxymethylcellulose‐stabilized collagenous rhOP‐1 device—a novel carrier biomaterial for the repair of mandibular continuity defects
Authors: Wang Huiming , Springer Ingo N. G. , Schildberg Hendrik , Acil Yahya , Ludwig Klaus , Rueger David R. , Terheyden Hendrik
Published: December 2003

Human recombinant osteogenic protein‐1 (rhOP‐1) is osteoinductive. Efforts are made to develop carrier biomaterials with improved space‐keeping properties. Bovine collagen type I matrix charged with rhOP‐1 was suggested to be an advantageous device of relative liquid quality. We hypothesized that the addition of carboxymethylcellulose (CMC) may stabilize the device and facilitate the regeneration of mandibular continuity defects without further addition of mineralized carrier materials. To test this hypothesis, the anatomical shape, functional remodeling, and mechanical stability of such bony regenerates were evaluated in the course of an animal experiment. Mandibular continuity defects of 5 cm in size were created in five Göttingen minipigs on one side (contralateral hemimandible: control) and bridged with titanium plates. Four animals were treated with the rhOP‐1 device (3000 μg rhOP‐1, 2 g collagen, 1 g CMC), and one animal was treated with a placebo device omitting rhOP‐1. After 12 weeks of experimental period, bony continuity was reestablished in rhOP‐1‐treated hemimandibles. The bony regenerates were of good anatomical shape, volume, and functional remodeling. Placebo treatment led to insufficient bony regenerates of significant lower bone volume (volume in 3D‐CT scan 29.81 cm3 vs 8.85 cm3). To produce 1 mm of bending, 1972 N were needed for rhOP‐1‐treated hemimandibles, 2617 N for control hemimandibles, and 642 N for the placebo treated hemimandible. CMC stabilization of collagen carrier biomaterials for rhOP‐1 provides good plasticity as well as excellent space‐keeping properties and may not interfere with osteoinduction. The results of this preliminary study suggest that the applied rhOP‐1 device offers a potential option for further studies on the reconstruction of mandibular defects. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 68A: 219–226, 2004
Effects of multigrooved surfaces on osteoblast‐like cells in vitro: Scanning electron microscopic observation and mRNA expression of osteopontin and osteocalcin
Authors: Matsuzaka K. , Yoshinari M. , Shimono M. , Inoue T.
Published: December 2003

This study evaluated the behavior of osteoblast‐like cells on multigrooved surfaces consisting of a combination of microgrooves and macrogrooves. A polystyrene substrate was fabricated with multigrooves with 90‐degree, V‐shaped microgrooves with a 2‐μm pitch cut on trapezoidal macrogrooves, which had a 50‐μm ridge width, a 50‐μm wall width, a 50‐μm bottom width, and 25‐μm depth. Smooth polystyrene substrates were also prepared as controls. Rat bone marrow cells were cultured as osteoblast‐like cells on the substrates for morphological evaluation using a scanning electron microscope, and for biochemical evaluation using the quantitative reverse transcriptase‐polymerase chain reaction technique for osteopontin and osteocalcin mRNA expression. After 8 days of incubation, the osteoblast‐like cells were aligned parallel to the surface grooves on the multigrooved substrates. After 16 days of incubation, a dense mineralized extracellular matrix (ECM) was produced along the multigrooves. The ECM on the multigrooved surface appeared oriented more in the direction of the grooves than on the smooth surface, and trapezoid‐shaped macrogrooves of the ECM were cast upside down. Although there were not significant differences, the osteopontin and osteocalcin mRNA expressions of the osteoblast‐like cells on the multigrooved surfaces tended to be higher than on smooth surfaces. These results suggest that multigrooves could be used to control the orientation of mineralized ECM as well as of cells, and also to enhance the production of mineralized ECM. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 68A: 227–234, 2004
Immobilized concentration gradients of nerve growth factor guide neurite outgrowth
Authors: Kapur Terri Adams , Shoichet Molly S.
Published: December 2003

Axons are guided to their targets by a combination of haptotactic and chemotactic cues. We previously demonstrated that soluble neurotrophic factor concentration gradients guide axons in a model system. In an attempt to translate this model system to a device for implantation, our goal was to immobilize a stable neurotrophic concentration gradient for axonal (or neurite) guidance. Nerve growth factor (NGF) was immobilized within poly(2‐hydroxyethylmethacrylate) [p(HEMA)] microporous gels using a gradient maker. The NGF was stably immobilized, with only ∼0.05% of the amount originally incorporated into the gel released over an 8‐day period. Immobilized NGF was bioactive: the percent of PC12 cells extending neurites on NGF‐immobilized p(HEMA) gels was 16 ± 2%, which was statistically the same as those exposed to soluble NGF (22 ± 6%). We were able to predict and reproducibly create stable NGF concentration gradients in the gel. At an NGF concentration gradient of 357 ng/mL/mm, PC12 cell neurites were guided up the gradient. The facile, flexible, and reproducible nature of this method allowed us to translate soluble growth factor gradient models to stable growth factor gradient devices that may ultimately enhance axonal guidance and regeneration in vivo. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 68A: 235–243, 2004
Substrate‐dependent cellular behavior of Swiss 3T3 fibroblasts and activation of Rho family during adhesion and spreading processes
Authors: Kato Shinya , Kidoaki Satoru , Matsuda Takehisa
Published: December 2003

Recent biochemical studies revealed that intracellular Rho guanosine triphosphatases (Rho, Rac1, and Cdc42) are key regulatory molecules that link surface receptors to cytoskeletal organization and regulation of cell shape/morphology/motility. In this study, Swiss 3T3 fibroblasts were cultured on three representative substrates [tissue culture polystyrene dishes, nontreated polystyrene, and poly(ethylene terephthalate)] for 24 h after plating. Time‐dependent changes in cell shape, morphology, cytoskeletal dynamics, and motility as well as Rho family activities were determined on each substrate. The cells on tissue culture polystyrene and on poly(ethylene terephthalate), which induced rapid and relatively rapid cell spreading, respectively, expressed Rac1 and Cdc42 activities continuously during the observation period. In contrast, such activities were suppressed in cells on polystyrene, which induced slow spreading but the highest cell motility compared with the other two substrates. Although a clear‐cut relationship between cellular behavior and Rho family activation was not obtained, substrate‐dependent coordinated control of cellular activities by Rho family is discussed. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 68A: 314–324, 2004
Cytotoxicity evaluation of ceramic particles of different sizes and shapes
Authors: Yamamoto Akiko , Honma Rieko , Sumita Masae , Hanawa Takao
Published: December 2003

When artificial hip or knee joints are implanted in the human body, they release metallic, ceramic, and polymeric debris into the surrounding tissues. The toxicity of the released particles is of two types: chemical, caused by the released soluble ions and monomers, and mechanical, a result of mechanical stimulation produced by the insoluble particles. In this study, the cytotoxicity of particles of TiO2, Al2O3, ZrO2, Si3N4, and SiC for murine fibroblasts and macrophages were examined to evaluate just their mechanical toxicity because these particles are not expected to release soluble metal ions. Different sizes and shapes of TiO2 particles were used to evaluate the effect of size and shape on particle cytotoxicity. The results suggest that the cytotoxicity of ceramic particles does not depend on their chemical species. Cytotoxicity levels were lower than those of corresponding metal ions, indicating that the mechanical toxicity of particles is lower than the chemical toxicity of released soluble ions and monomers. The differences in size did not affect the mechanical toxicity of these particles. The dendritic particles had a higher cytotoxicity level for macrophages than did spindle and spheric particles. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 68A: 244–256, 2004
Fibronectin interactions with osteoblasts: Identification of a non–integrin‐mediated binding mechanism using a real‐time fluorescence binding assay
Authors: Sim Bushra , Cladera Josep , O'Shea Paul
Published: December 2003

Fibronectin (Fn) is an extracellular matrix protein that interacts with specific integrins on the cell surface, initiating signal transduction processes that lead to a reorganization of the cytoskeleton and the assembly of focal adhesions. Cell surface proteoglycans or glycosaminoglycans (GAGs) such as heparan sulfate are also known to participate in the interaction of Fn with the cell surface by binding to two different heparin‐binding domains. The influence of Fn and GAGs on the spreading and differentiation of human osteoblasts was also previously described. In the current work, a method developed in our laboratory is established to evaluate the interaction between Fn and human osteoblasts and the influence of GAGs on such interactions. This technique makes use of fluoresceinphosphatidylethanolamine (FPE) such that when inserted into the lipidic bilayer, it acts as a fluorescent indicator of membrane interactions. The results indicate that the binding profile of Fn with the osteoblast cell surface is best represented by a hyperbolic single binding site model with a membrane affinity of 120 nM. Removal of cell surface heparan sulfate by treatment with heparitinase indicates that the cell surface moiety is directly involved in the binding process. Studies directed to assess the influence of heparin on the interaction of Fn with osteoblasts reveal that although it does not hamper Fn binding to the cell surface, it blocks the initial attachment to Fn‐coated surfaces, indicating that binding to the integrin receptor alone is not enough to promote cell attachment but that the participation of the cell‐surface GAGs is also a necessary condition. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 68A: 352–359, 2004
Gingival organotypic culture and langerhans cells: A tool for immunotoxicologic experiments
Authors: Lamarque Stéphane , Pellen‐Mussi Pascal , Rougier Nathalie , Le Lan Jacky , Chesne Christophe , Bonnaure‐Mallet Martine
Published: December 2003

Langerhans cells (LCs) are dendritic cells localized in epidermis and mucosal tissues, where they are responsible for triggering the immune response. To study LCs in the oral epithelium, organotypic cultures were prepared using gingival explants. Immunochemical techniques using anti‐CD1a, anti‐HLA‐DR, and anti‐Langerin antibodies were used to detect and quantify LCs at various times. Observations were made by light and confocal microscopy. Quantification studies showed that there is a statistically significant drop in LC numbers in the epithelial tissue after 96 h of incubation. Gingival organotypic cultures thus are a good model for studying the migration of LCs and their involvement in contact hypersensitivity and periodontal diseases. The model offers potential utility as a tool for the study of periodontal tissue in the presence of different stimuli and for conducting immunotoxicologic experiments. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 68A: 257–263, 2004
Use of an intramedullary in vivo model to study bone formation and maintenance in ceramic porous domains
Authors: Pabbruwe Moreica B. , Standard Owen C. , Sorrell Charles. C. , Howlett C. Rolfe
Published: December 2003

Tissue ingrowth, differentiation, and osteogenesis in a porous bioinert bioceramic were studied using an intramedullary model. Pure alumina tubes (1.3 mm outer diameter, 0.6 mm inner diameter, 15 mm length) were implanted in the femoral medullary canal of young female rats for 4, 6, 8, 12, and 16 weeks. Tissues present within each tube were characterized by histology and quantified by histomorphometry. A tissue front consisting of undifferentiated mesenchymal cells, fibrovascular tissue, osteoid, woven bone, and marrow penetrated the tube from both ends. Behind the front, woven bone remodeled to produce a thin layer of lamellar bone that lined the tube walls the entire distance to the tube ends and enclosed a marrow‐filled lumen. The front was considered to represent the differentiation cascade from mesenchymal cells to fibrovascular tissue to osteoid to woven bone and marrow to lamellar bone and marrow. The fronts advanced into the tube with time such that, by 16 weeks, they were close to meeting or had met. In several instances, the tube was completely lined with a thin layer of mature lamellar bone continuous between the two ends and enclosing marrow. This configuration was considered to be the final equilibrium of tissues within the tube. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 68A: 305–313, 2004
Peripheral nerve regeneration by microbraided poly(L‐lactide‐co‐glycolide) biodegradable polymer fibers
Authors: Bini T. B. , Gao Shujun , Xu Xiaoyun , Wang Shu , Ramakrishna S. , Leong Kam. W.
Published: December 2003

Tiny tubes with fiber architecture were developed by a novel method of fabrication upon introducing some modification to the microbraiding technique, to function as nerve guide conduit and the feasibility of in vivo nerve regeneration was investigated through several of these conduits. Poly(L‐lactide‐co‐glycolide) (10:90) polymer fibers being biocompatible and biodegradable were used for the fabrication of the conduits. The microbraided nerve guide conduits (MNGCs) were characterized using scanning electron microscopy to study the surface morphology and fiber arrangement. Degradation tests were performed and the micrographs of the conduit showed that the degradation of the conduit is by fiber breakage indicating bulk hydrolysis of the polymer. Biological performances of the conduits were examined in the rat sciatic nerve model with a 12‐mm gap. After implantation of the MNGC to the right sciatic nerve of the rat, there was no inflammatory response. One week after implantation, a thin tissue capsule was formed on the outer surface of the conduit, indicating good biological response of the conduit. Fibrin matrix cable formation was seen inside the MNGC after 1 week implantation. One month after implantation, 9 of 10 rats showed successful nerve regeneration. None of the implanted tubes showed tube breakage. The MNGCs were flexible, permeable, and showed no swelling apart from its other advantages. Thus, these new poly(L‐lactide‐co‐glycolide) microbraided conduits can be effective aids for nerve regeneration and repair and may lead to clinical applications. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 68A: 286–295, 2004
Osteointegration of bioactive glass‐coated and uncoated zirconia in osteopenic bone: An in vivo experimental study
Authors: Aldini N. Nicoli , Fini M. , Giavaresi G. , Martini L. , Dubini B. , Bossi M. G. Ponzi , Rustichelli F. , Krajewski A. , Ravaglioli A. , Mazzocchi M. , Giardino R.
Published: December 2003

In elderly and osteoporotic patients an age‐related loss of osteoinductivity could be the biological cause of implant failure regardless of the high quality of the implanted device. yttria stabilized tetragonal zirconia (YSTZ), either coated with the bioactive glass named RKKP bioglaze® (RKKP) or uncoated, was implanted in the distal femurs of sham‐operated and ovariectomized female rats. Animals were sacrificed at 30 and 60 days. Histomorphometry and microhardness tests were performed to assess osteointegration rate as well as bone quality around the implants. Significant decreases (p < 0.0005) in trabecular bone volume, BV/TV (41%), trabecular bone surface BS/TV (33%), trabecular thickness Tb.Th (20%), and trabecular number Tb.N (32%), together with a significant increase in trabecular separation Tb.Sp (184%), were found for the osteopenic rats compared with the sham‐operated rats. At both experimental times the RKKP coating ensured a better osteointegration rate with higher AI values than the uncoated YSTZ, even when osteopenic rats were used (48% at 30 days and 12% at 60 days). No differences were observed at the bone‐biomaterial interfaces for either material when comparing sham‐operated with osteopenic rats. The present results demonstrate that the RKKP bioactive glass used as a coating ensures a high osteointegration rate even in osteoporotic bone, which is already visible from postoperative day 30 and is still apparent on day 60. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 68A: 264–272, 2004
Ultrastructure and nanomechanical properties of cementum dentin junction
Authors: Ho S. P. , Balooch M. , Goodis H. E. , Marshall G. W. , Marshall S. J.
Published: December 2003

The attachment between cementum and dentin has been given several definitions and nomenclature, including: interzonal layer, intermediate cementum, collagen hiatus, Hopewell‐Smith's hyaline layer, and more commonly, cementum–dentin junction (CDJ). Understanding the attachment of two structurally dissimilar hard tissues such as cementum and dentin defined by a junction may provide information necessary to engineer functionally graded materials that can be used for efficient tooth restorations in clinical dentistry and other bioengineering applications. Hence, in this study, as a first step toward understanding the CDJ using a biomechanical approach, it was hypothesized that the CDJ between cementum and dentin is a wide zone with mechanical properties significantly lower than the neighboring tissues. The structure of the CDJ was studied using an atomic force microscope (AFM), and site‐specific mechanical response of the three regions; cementum, CDJ, and dentin were determined using an AFM‐nanoindenter under dry and wet conditions. The AFM results of the CDJ demonstrated a valley under dry conditions and a peak under wet conditions. The magnitude of the depth of the valley was approximately the same as the height of the peak of the CDJ, ranging from 10 to 40 μm. The nanomechanical properties under dry conditions indicated no significant difference (p > 0.05) in elastic modulus and hardness of the CDJ (Er = 17.5 ± 2.7 GPa, H = 0.6 ± 0.1 GPa) and cementum (Er = 18.7 ± 2.5 GPa, H = 0.6 ± 0.1 GPa). The mechanical properties of the CDJ were significantly lower (p ≪ 0.05) than dentin (Er = 19.9 ± 2.9 GPa, H = 0.6 ± 0.1 GPa) under dry conditions. However, under more relevant hydrated conditions, the mechanical properties of CDJ (Er 3.0 ± 0.7 GPa, H = 0.1 ± 0.0 GPa) were significantly lower (p ≪ 0.05) than those of cementum (Er 6.8 ± 1.9 GPa, H = 0.2 ± 0.1 GPa) and dentin (Er 9.4 ± 2.3 GPa, H = 0.3 ± 0.1 GPa). Based on the results from this study, it can be concluded that the CDJ can be regarded as a wide zone containing large quantities of proteins including collagen that contribute to hydration and significantly reduce mechanical properties, compared with the adjacent hard tissues, cementum, and dentin. The lower mechanical properties of the CDJ may make it possible for it to redistribute occlusal loads to the alveolar bone. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 68A: 343–351, 2004
Surface analyses of micro‐arc oxidized and hydrothermally treated titanium and effect on osteoblast behavior
Authors: Zhang Y. M. , Bataillon‐Linez P. , Huang P. , Zhao Y. M. , Han Y. , Traisnel M. , Xu K. W. , Hildebrand H. F.
Published: December 2003

Osteoblast adhesion on the implant material surface is essential for the success of any implant in which osteointegration is required. Surface properties of implant material have a critical role in the cell adhesion progress. Titanium and its alloys are widespread and increasingly used as implant material in dentistry and orthopedics because of their excellent biocompatibility, which is attributed to a passive layer of TiO2 on the surface. In this study, the micro‐arc oxidizing (MAO) and hydrothermally synthesizing (HS) methods were used to modify the TiO2 layer on the titanium surface. The surface microstructure was observed by scanning electron microscopy. The surface energy was assessed. The mouse osteoblastic cell line (MC3T3‐E1) was seeded on the treated surfaces to evaluate their effect on cell behavior. This included cell adhesion kinetics, cell proliferation, cell morphology, and cytoskeletal organization. The surface structure of MAO samples exhibited micropores with a diameter of 1–3 μm, whereas the MAO–HS‐treated samples showed additional multiple crystalline microparticles on the microporous surface. The surface energy of MAO and MAO–HS was higher than that of titanium. The cell adhesion rate was higher on the MAO–HS surface than on the MAO and titanium surface, but without any significant difference between them. After 3 days of culture, cells proliferated significantly more on the MAO and titanium surface than on the MAO–HS surface. The cytoskeletal organization was analyzed by actin and vinculin staining on all the samples. We conclude that the MAO and MAO–HS methods change the surface energy of TiO2 layer on the titanium surface. This may have an influence on the initial cell attachment. Other surface characteristics may be involved in the cell proliferation, which is different from cell attachment on the sample surface. A longer‐duration cell experiment should be conducted to see the effect on cell differentiation. Future in vivo evaluation may give further evidence to optimize the surface character of this kind of implant material. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 68A: 383–391, 2004
Gene expression changes in BALB/3T3 transformants induced by poly(L‐lactic acid) or polyurethane films
Authors: Matsuoka Atsuko , Tsuchiya Toshie
Published: December 2003

We performed DNA microarray analysis on two BALB/3T3 transformants (A5 and A6) induced by polyurethane (PU) film, two (L11 and L21) induced by biodegradable poly(L‐lactic acid) (PLLA) film, and the parental cells. The transforming ability of the cells was in the order A5 < A6 < L21 < L11. In all, 1176 cancer‐related genes were up‐ or down‐regulated in at least one transformant. Those that were markedly up‐regulated were c‐fos protooncogene, FBJ osteosarcoma oncogene B, and Jun oncogene; those markedly down‐regulated were pleiotrophin, histidine triad nucleotide‐binding protein, protein kinase C iota, and large multifunctional protease 7. A common function of proteins encoded by genes that underwent marked expression changes was bone formation. The genes were c‐fos, FBJ osteosarcoma, Jun, pleiotrophin, a disintegrin‐like and metalloprotease with TS‐1 motif protein 1. This finding was consistent with the tumor formation in the 2‐year PLLA or PU subcutaneous implantation into rats. The number of genes that underwent marked expression change in each transformant was consistent with its malignancy. PLLA induced more malignant transformants than PU, especially in relation to osteosarcoma‐like gene expression. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 68A: 376–382, 2004
Tissue adhesiveness and host response of in situ photopolymerizable interpenetrating networks containing methylprednisolone acetate
Authors: Zilinski Jodi L. , Kao Weiyuan John
Published: December 2003

Interpenetrating networks (IPNs) of varying formulations were investigated as candidates for an in situ photopolymerizable drug delivery matrix containing poly(ethylene glycol) diacrylate and gelatin. The anti‐inflammatory agent methylprednisolone acetate was loaded into the IPN. Bond strength between the IPN and tissue (i.e., muscle, dermis, skin) was determined by a modified American Society for Testing and Materials peel test at constant peel rate. The IPNs provided adhesion values of up to 5.7N, which were three‐ to fivefold lower than that of the commercial tissue bioadhesive. The subcutaneous cage implant system was utilized to assess material host response and drug efficacy in vivo. IPN formulations elicited a more intense acute inflammatory response than the empty cage controls. Methylprednisolone acetate loaded within the IPNs lowered the level of inflammatory response to levels that were comparable to the empty cage baseline controls. In conclusion, a methodology was developed to quantify the tissue adhesiveness of an in situ photopolymerized IPN matrix containing anti‐inflammatory agents. The efficacy of drug‐loaded IPN in affecting the host inflammatory response was demonstrated in vivo. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 68A: 392–400, 2004
Administration of bone marrow cells into surgically induced fibrocollagenous tunnels induces angiogenesis in ischemic rat hindlimb model
Authors: Padilla Luis , Krötzsch Edgar , Schalch Paul , Figueroa Siegfried , Miranda Adriana , Rojas Enrique , Esperante Sandro , Villegas Fernando , De La Garza Anabel S. , Di Silvio Mauricio
Published: December 2003

We established a comparative model of angiogenic induction in previously formed fibrocollagenous tunnels in rat inner thigh muscles. A unilateral hindlimb chronic ischemia model was performed in male Sprague‐Dawley rats. A device was then inserted in the central portion of the inner thigh muscles. Vascularity in the ischemic limb was determined by means of an angiographic score, capillary/fiber ratio, and endothelial proliferation by histochemistry and immunohistochemistry. Autologous transplant of bone marrow, vascular endothelial growth factor (VEGF), or collagen‐polyvinylpyrrolidone plus heparin induced significant vascularization of the ischemic hindlimb when compared to saline solution. However, the bone marrow group presented a higher angiographic score than the other two. No differences among groups were observed in capillary/fiber ratio or proliferation, except for the VEGF group, where capillary proliferating cells were significantly higher than in controls. Based on these results, bone marrow‐derived progenitor cells may constitute a safe and viable alternative for the induction of therapeutic angiogenesis. © 2003 Wiley‐Liss, Inc. MICROSURGERY 23:568–574 2003
Effects of hyaluronic acid on peripheral nerve scarring and regeneration in rats
Authors: Özgenel Güzin Yeşim
Published: December 2003

The purpose of this experimental study was to investigate the effects of topical applications of hyaluronic acid on peripheral nerve scarring and regeneration in an adult rat model. After the right sciatic nerves of 48 rats were transected and immediately repaired, nerves were randomly divided into two groups. Nerves to which were applied hyaluronic acid comprised the experimental group, and nerves to which were applied saline comprised the control group. Perineural scarring was evaluated at 4 and 12 weeks macroscopically and histologically. Nerves treated with hyaluronic acid demonstrated significant reduction in perineural scar thickness (P < 0.05, Student's t‐test). Histomorphologic nerve analysis, electrophysiologic studies, muscle mass evaluation, and serial functional walking‐track analysis were performed for evaluation of peripheral nerve regeneration at 12 weeks. The results showed better conduction velocities, increased axon‐fiber diameter, and faster functional recovery in hyaluronic acid‐treated nerves (P < 0.05, Student's t‐test). In conclusion, hyaluronic acid appears to be effective in preventing perineural scar formation, resulting in enhancement of peripheral nerve regeneration. © 2003 Wiley‐Liss, Inc. MICROSURGERY 23:575–581 2003
C1‐esterase inhibitor and a novel peptide inhibitor improve contractile function in reperfused skeletal muscle
Authors: Toomayan Glen A. , Chen Long‐En , Jiang Hai‐Xiang , Qi Wen‐Ning , Seaber Anthony V. , Frank Michael M. , Urbaniak James R.
Published: December 2003

To determine the role of inhibition of complement activation in the contractile function of skeletal muscle ischemia‐reperfusion (I/R) injury, the rat extensor digitorum longus (EDL) muscles underwent 3 h ischemia and received human C1‐esterase inhibitor (C1‐INH, 100 IU/kg), a synthetic C1q A chain peptide with a similar inhibitory effect on activated C1 (peptide, 5 mg/kg), or human serum albumin control. Results showed a significant overall increase in tetanic contractile forces of the reperfused EDL in both C1‐INH and peptide groups compared to controls. Maximum improvement occurred with peptide treatment at 120‐Hz stimulation, with an increase in force from 38 ± 4% of normal in controls to 52 ± 4% in peptide‐treated rats. There were no significant differences between C1‐INH and peptide groups. Plasma C3 and C4 activities were significantly increased in both treated groups, suggesting inhibition of complement activation. Our results suggest that complement activation is involved in I/R injury, and inhibition of complement activation may therefore represent a potential therapeutic approach to reducing or preventing I/R injury. © 2003 Wiley‐Liss, Inc. MICROSURGERY 23:561–567 2003
Comparison of different managements of large superficial veins in distally based fasciocutaneous flaps with a veno‐neuro‐adipofascial pedicle: An experimental study using a rabbit model
Authors: Chang Shi‐Min , Gu Yu‐Dong , Li Ji‐Feng
Published: December 2003

The role of large superficial veins in the survival of a distally based fasciocutaneous flap with a veno‐neuro‐adipofascial pedicle was studied in a rabbit model. A sural veno‐neuro‐fasciocutaneous flap model (6 × 2 cm) with a distally based lesser saphenous veno‐neuro‐adipofascial pedicle (1.5 cm) was established. Fifteen rabbits were randomly divided into three groups with 10 flaps in each group. In group I, the distal lesser saphenous vein was left open (venous inflow remained) after the flap was raised. In group II, the lesser saphenous vein was ligated in the pedicle (no venous inflow). In group III, the venous pedicle was left open in the pedicle, and the proximal end was microsurgically anastomosed to the recipient vein (outflow established). Intravenous pressure, flap survival, and histology were examined. The results showed that the values of intravenous pressure in group I were significantly higher than in group II (P < 0.001). The mean flap survival rate of group III (94.5%) was significantly higher (P < 0.001) than of groups I (22.7%) and II (55.5%). Histology showed that the lesser saphenous vein in group I was extremely dilated and filled with thrombosis. This experiment demonstrated that establishing a superficial venous outflow channel by anastomosis at the proximal end, or interrupting the inflow channel by ligation at the distal pedicle, may significantly improve the survival rate of distally based veno‐neuro‐fasciocutaneous flaps. © 2003 Wiley‐Liss, Inc. MICROSURGERY 23:555–560 2003
New experimantal composite flap model in rats: Gluteus maximus‐tensor fascia lata osteomuscle flap
Authors: Nasir Serdar , Aydin Asim , Kayikçioğlu Aycan , Sökmensüer Cenk , Çobaner Azem
Published: December 2003

Experimental animal models need to be developed for studies of composite flaps that have often recently been used for defects of both bone and soft tissues. A consistent anatomy, simple surgical technique, and reliable blood flow are essential for the success of experimental flap studies. Here we propose a gluteus maximus‐tensor fascia lata osteomuscle flap in rats as a model of these qualities. Gluteus maximus and tensor fascia lata muscles and the adjacent iliac bone segment were combined as a lateral circumflex femoral artery‐based flap. To test the reliability of this composite flap, three types of composite tissues were harvested and replaced: osteomusculocutaneous flap, osteomuscle flap, and osteomuscle composite graft. The osteomusculocutaneous flap was elevated by including a skin island over the gluteal region. The osteomuscle graft was formed by deliberately dividing the vascular pedicle of the osteomuscle flap. Direct observation revealed complete necrosis of the skin islands in all osteomusculocutaneous flaps. Microangiography of the flap demonstrated that both muscles and the attached bone were supplied by the pedicle. Dye studies with nitro blue tetrazolium (NBT) and India ink demonstrated dye uptake in both muscle and bone components in osteomuscle flaps. Histological examinations also demonstrated the viability of both tissues only in the flap group. Bone scintigraphy performed in flaps on postoperative day 7 demonstrated radionuclide uptake, confirming perfusion of the bony segment. The gluteus maximus‐tensor fascia lata osteomuscle flap is a reliable and simple model for composite flap studies that offers the following advantages: 1) it is a new composite flap which includes bone, 2) it can be dissected easily with the naked eye, without using the microscope, 3) it has a long pedicle for flap displacement, and 4) it is a small animal model. © 2003 Wiley‐Liss, Inc. MICROSURGERY 23:582–588 2003
Microsurgical treatment for bilateral thumb defect: Five case reports
Authors: Xu Lei , Gu Yu‐Dong , Xu Jian‐Guang , Rui Yong‐Jun , Shou Kui‐Sui
Published: December 2003

The authors present a new and efficient treatment for reconstruction of bilateral defective thumbs by different configured toe‐tissuestransplantations in a single stage, including bilateral second‐toe transfer in 2 cases, bilateral hallux wrap‐around flap transfer in 1 case, bilateral modified hallux wrap‐around flap transfer in 1 case, and combined second toe with island flap with neurovascular pedicles from the proximal and dorsal aspect of the index finger transfer in 1 case. In total, eight transferred tissues survived uneventfully after circulation monitor and medicine administration according to the rules of microsurgery, and in two other transferred toe tissues, temporary circulation crises occurred. Over a 1‐year follow‐up, the satisfactory appearance and excellent function of the reconstructed bilateral thumbs were noted. For ensuring the success of the procedure, the authors emphasize the establishment of a double artery supply and venous return‐flow systems and the modification of the hallux wrap‐around flap dissection and tendon repair. Meanwhile, three‐stage systemically functional rehabilitations also improved functional restoration of reconstructed thumbs. © 2003 Wiley‐Liss, Inc. MICROSURGERY 23:547–554 2003
Crossover between the cell size and wavelength of the incident radiation in a metamaterial
Authors: Prati Enrico
Published: January 2004

One of the strongest limitations in metamaterials technology is the constraint of the lattice constant to be much smaller than the incident wavelength. This paper describes an experiment, based on SSRs at 50 GHz, to restore the resonant behavior even if such a constraint is not fulfilled, thus suggesting a way to reach infrared and visible frequencies. © 2004 Wiley Periodicals, Inc. Microwave Opt Technol Lett 40: 269–272, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.11349
Folded‐loop antenna with a reflector for mobile handsets at 2.0 GHz
Authors: Hirata Akimasa , Adachi Takahiko , Shiozawa Toshiyuki
Published: January 2004

A folded‐loop antenna with a reflector for mobile handsets at the 2.0‐GHz band is analyzed, taking the effect of the human head into account. The reflector is arranged between the human head and the driver. The width and height of the reflector are chosen to be slightly smaller and larger than those of the driver, respectively. Based upon numerical investigations, this antenna is found to enhance radiation efficiency by 20% and reduce peak specific absorption rates (SARs) averaged over 1 g and 10 g of tissues by 70%–85%. © 2004 Wiley Periodicals, Inc. Microwave Opt Technol Lett 40: 272–275, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.11350