A case of infectious heterotopic ossification in the appendectomy scar, which formed an inflammatory granuloma.

Inflammatory granulomas often develop in surgical scars due to the presence of foreign bodies, such as sutures. These granulomas are called Schloffer's tumors. Here, we report a case of heterotopic ossification(HO) in an appendectomy scar that formed an inflammatory granuloma following HO infection. A 90-year-old woman was referred to our hospital with a chief complaint of a painful mass in the right lower quadrant of her abdomen. She had a history of acute appendicitis, for which she underwent an appendectomy approximately 70 years previously. Imaging studies demonstrated a tumor containing a linear-shaped agent located in the abdominal wall under the surgical scar where the appendectomy was performed. She was then diagnosed with Schloffer's tumor, for which she underwent surgical resection. However, histopathological examination revealed that the tumor was a fibrous connective tissue mass with a lamellar bone inside.

Polymer networks with bicontinuous gradient morphologies resulting from the competition between phase separation and photopolymerization.

Poly(ethyl acrylate)/poly(methyl methacrylate) (PEA/PMMA) polymer networks (IPNs) with spatially graded bicontinuous morphology were designed and controlled by taking advantage of the spinodal decomposition process induced by photopolymerization of the MMA monomer. Spatial gradients of the quench depth, induced by the gradients of light intensity, were generated along the path of the excitation light travelling through the mixture. Bicontinuous structures with uniaxial gradient of characteristic length scales were obtained by two different methods: simply irradiating the mixture with strong light intensity along the Z-direction and using the so-called computer-assisted irradiation (CAI) method with moderate intensity to generate the light intensity gradient exclusively in the XY plane. These experimental results suggest that the combination of these two irradiation methods could provide polymer materials with biaxially co-continuous gradient morphology. An analysis method using the concept of spatial correlation function was developed to analyze the time-evolution of these graded structures. The experimental results obtained in this study suggest a promising method to design gradient polymers in the bulk state (3D) as well as on the surface (2D) by taking advantage of photopolymerization.

Papilla Formation in Response to Computer-Assisted Implant Surgery and Immediate Restoration.

This retrospective analysis was undertaken to evaluate the effect of immediate implant restoration using a computer-assisted technique in partially edentulous sites on interimplant and intertooth bone level stability and papilla formation. Nine partially edentulous patients received a total of 23 implants that supported immediately placed implant restorations. Planning was accomplished using a radiographic guide, which allowed visualization of the emergence profile from the platform of the implant to the cervical of the planned restoration. Guided implants were placed according to the manufacturer's instructions, and restorations were screw retained directly to the implant. Multiple implants were splinted at surgery with autopolymerizing resin. Measurements were made at a mean of 545 days (range 288-958) postoperatively on the basis of radiographs and photographs. Measures were: (1) distance from bone crest to platform, (2) bone crest to contact point, (3) interimplant distance at the outer diameter of the platform, and (4) papilla from highest point to a reference line. At follow-up time, the bone ridge was located higher than the implant platform (mean 0.57 mm) compared to implants whose interimplant distance was less than 3 mm (mean 0.27 mm). Mean increase of the bone level between insertion and approximate 1-year follow-up was 0.047 mm. The mean distance from the contact point to bone was 2.39/3.93 mm postoperatively, resulting in 91/71% papilla fill between implants and between implant and adjacent tooth, respectively. Computer-assisted surgery with the preplanned immediate restoration seems to be an effective method to minimize bone loss at the implant platform resulting in support for papilla.

Why guided when freehand is easier, quicker, and less costly?

Computer-assisted implant planning and subsequent production of a surgical template based on this plan has gained attention because it provides restoratively driven esthetics, patient comfort, satisfaction, and the option of flapless surgery and immediate restoration. However, it adds expense and requires more time. Another significant but not so apparent advantage may be improved survival and success over freehand techniques in types III and IV bone. This retrospective analysis was undertaken to examine that possibility. It reports 1-year outcome for 80 implants in 27 consecutively presenting patients treated over a 7-year period using computer-assisted techniques across all bone qualities in commonly encountered treatment indications in private practice. Implants were placed to support single teeth, small bridges, and complete arch restorations in exposed or immediately restored applications, based on primary stability as determined by insertion torque, resonance frequency analysis, and Periotest. For the 80 implants supporting 35 restorations, the median observation period is 2.66 years; 73 implants supporting prostheses in 22 patients had readable radiographs at 1 year. There was a 1-year overall implant survival and a success rate of 100%. Radiographic analysis demonstrated the change in bone level from the platform at 1-year is less than 2 mm. Intra-operative median measurements of primary stability were insertion torque, 40 Ncm; resonance frequency, 76 ISQ; and Periotest, -3. All intra-operative measurements were consistent for acceptable primary stability regardless of bone density. Restoratively driven diagnosis and precision planning and initial fit were possible with computer-assisted techniques resulting in the achievement of high primary stability, even in areas of less dense bone. The ability to plan implant position, drill sequence, and implant design on the basis of predetermined bone density gives the practitioner enhanced pretreatment information which can lead to improved outcome.

Alginate-dependent gene expression mechanism in Sphingomonas sp. strain A1.

Sphingomonas sp. strain A1, a Gram-negative bacterium, directly incorporates alginate polysaccharide into the cytoplasm through a periplasmic alginate-binding protein-dependent ATP-binding cassette transporter. The polysaccharide is degraded to monosaccharides via the formation of oligosaccharides by endo- and exotype alginate lyases. The strain A1 proteins for alginate uptake and degradation are encoded in both strands of a genetic cluster in the bacterial genome and inducibly expressed in the presence of alginate. Here we show the function of the alginate-dependent transcription factor AlgO and its mode of action on the genetic cluster and alginate oligosaccharides. A putative gene within the genetic cluster seems to encode a transcription factor-like protein (AlgO). Mutant strain A1 (ΔAlgO mutant) cells with a disrupted algO gene constitutively produced alginate-related proteins. DNA microarray analysis indicated that wild-type cells inducibly transcribed the genetic cluster only in the presence of alginate, while ΔAlgO mutant cells constitutively expressed the genetic cluster. A gel mobility shift assay showed that AlgO binds to the specific intergenic region between algO and algS (algO-algS). Binding of AlgO to the algO-algS intergenic region diminished with increasing alginate oligosaccharides. These results demonstrated a novel alginate-dependent gene expression mechanism. In the absence of alginate, AlgO binds to the algO-algS intergenic region and represses the expression of both strands of the genetic cluster, while in the presence of alginate, AlgO dissociates from the algO-algS intergenic region via binding to alginate oligosaccharides produced through the lyase reaction and subsequently initiates transcription of the genetic cluster. This is the first report on the mechanism by which alginate regulates the expression of the gene cluster.

Protective role for TLR4 signaling in atherosclerosis progression as revealed by infection with a common oral pathogen.

Clinical and epidemiological studies have implicated chronic infections in the development of atherosclerosis. It has been proposed that common mechanisms of signaling via TLRs link stimulation by multiple pathogens to atherosclerosis. However, how pathogen-specific stimulation of TLR4 contributes to atherosclerosis progression remains poorly understood. In this study, atherosclerosis-prone apolipoprotein-E null (ApoE(-/-)) and TLR4-deficient (ApoE(-/-)TLR4(-/-)) mice were orally infected with the periodontal pathogen Porphyromonas gingivalis. ApoE(-/-)TLR4(-/-) mice were markedly more susceptible to atherosclerosis after oral infection with P. gingivalis. Using live animal imaging, we demonstrate that enhanced lesion progression occurs progressively and was increasingly evident with advancing age. Immunohistochemical analysis of lesions from ApoE(-/-)TLR4(-/-) mice revealed an increased inflammatory cell infiltrate composed primarily of macrophages and IL-17 effector T cells (Th17), a subset linked with chronic inflammation. Furthermore, enhanced atherosclerosis in TLR4-deficient mice was associated with impaired development of Th1 immunity and regulatory T cell infiltration. In vitro studies suggest that the mechanism of TLR4-mediated protective immunity may be orchestrated by dendritic cell IL-12 and IL-10, which are prototypic Th1 and regulatory T cell polarizing cytokines. We demonstrate an atheroprotective role for TLR4 in response to infection with the oral pathogen P. gingivalis. Our results point to a role for pathogen-specific TLR signaling in chronic inflammation and atherosclerosis.

Porphyromonas gingivalis accelerates inflammatory atherosclerosis in the innominate artery of ApoE deficient mice.

OBJECTIVE: Studies in humans support a role for the oral pathogen Porphyromonas gingivalis in the development of inflammatory atherosclerosis. The goal of this study was to determine if P. gingivalis infection accelerates inflammation and atherosclerosis in the innominate artery of mice, an artery which has been reported to exhibit many features of human atherosclerotic disease, including plaque rupture. METHODS AND RESULTS: Apolipoprotein E-deficient (ApoE-/-) mice were orally infected with P. gingivalis, and magnetic resonance imaging (MRI) was used to monitor the progression of atherosclerosis in live mice. P. gingivalis infected mice exhibited a statistically significant increase in atherosclerotic plaque in the innominate artery as compared to uninfected mice. Polarized light microscopy and immunohistochemistry revealed that the innominate arteries of infected mice had increased lipids, macrophages and T cells as compared to uninfected mice. Increases in plaque, total cholesterol esters and cholesterol monohydrate crystals, macrophages, and T cells were prevented by immunization with heat-killed P. gingivalis prior to pathogen exposure. CONCLUSIONS: These are the first studies to demonstrate progression of inflammatory plaque accumulation in the innominate arteries by in vivo MRI analysis following pathogen exposure, and to document protection from plaque progression in the innominate artery via immunization.

Pathogen-mediated inflammatory atherosclerosis is mediated in part via Toll-like receptor 2-induced inflammatory responses.

Studies in humans have established that polymorphisms in genes encoding the innate immune Toll-like receptors (TLRs) are associated with inflammatory atherosclerosis. In hyperlipidemic mice, TLR2 and TLR4 have been reported to contribute to atherosclerosis progression. Human and mouse studies support a role for the oral pathogen Porphyromonas gingivalis in atherosclerosis, although the mechanisms by which this pathogen stimulates inflammatory atherosclerosis via innate immune system activation is not known. Using a genetically defined apolipoprotein E-deficient (ApoE(-/-)) mouse model we demonstrate that pathogen-mediated inflammatory atherosclerosis occurs via both TLR2-dependent and TLR2-independent mechanisms. P. gingivalis infection in mice possessing functional TLR2 induced the accumulation of macrophages as well as inflammatory mediators including CD40, IFN-gamma and the pro-inflammatory cytokines IL-1 beta, IL-6 and tumor necrosis factor-alpha in atherosclerotic lesions. The expression of these inflammatory mediators was reduced in atherosclerotic lesions from P. gingivalis-infected TLR2-deficient (TLR2(-/-)) mice. These studies provide a mechanistic link between an innate immune receptor and pathogen-accelerated atherosclerosis by a clinically and biologically relevant bacterial pathogen.

Stimulation of Toll-like receptor 2 in human platelets induces a thromboinflammatory response through activation of phosphoinositide 3-kinase.

Cells of the innate immune system use Toll-like receptors (TLRs) to initiate the proinflammatory response to microbial infection. Recent studies have shown acute infections are associated with a transient increase in the risk of vascular thrombotic events. Although platelets play a central role in acute thrombosis and accumulating evidence demonstrates their role in inflammation and innate immunity, investigations into the expression and functionality of platelet TLRs have been limited. In the present study, we demonstrate that human platelets express TLR2, TLR1, and TLR6. Incubation of isolated platelets with Pam(3)CSK4, a synthetic TLR2/TLR1 agonist, directly induced platelet aggregation and adhesion to collagen. These functional responses were inhibited in TLR2-deficient mice and, in human platelets, by pretreatment with TLR2-blocking antibody. Stimulation of platelet TLR2 also increased P-selectin surface expression, activation of integrin alpha(IIb)beta(3), generation of reactive oxygen species, and, in human whole blood, formation of platelet-neutrophil heterotypic aggregates. TLR2 stimulation also activated the phosphoinositide 3-kinase (PI3-K)/Akt signaling pathway in platelets, and inhibition of PI3-K significantly reduced Pam(3)CSK4-induced platelet responses. In vivo challenge with live Porphyromonas gingivalis, a Gram-negative pathogenic bacterium that uses TLR2 for innate immune signaling, also induced significant formation of platelet-neutrophil aggregates in wild-type but not TLR2-deficient mice. Together, these data provide the first demonstration that human platelets express functional TLR2 capable of recognizing bacterial components and activating the platelet thrombotic and/or inflammatory pathways. This work substantiates the role of platelets in the immune and inflammatory response and suggests a mechanism by which bacteria could directly activate platelets.

Favorable periodontal healing of 1-wall infrabony defects after application of calcium phosphate cement wall alone or in combination with enamel matrix derivative: a pilot study with canine mandibles.

BACKGROUND: Although various periodontal regenerative therapies are used, their effects on non-contained infrabony defects are unpredictable. Our previous studies showed that injectable, moldable, fast-setting calcium phosphate cement (CPC) promoted histocompatible periodontal healing in 3-wall intrabony defects. The present study evaluated healing patterns after surgical application of CPC walls with and without an enamel matrix derivative (EMD) in 1-wall infrabony defects in dogs. METHODS: One-wall infrabony defects (5 x 5 x 4 mm) were created surgically on the mesial and distal sides of bilateral mandibular fourth premolars in four beagle dogs. After elevating a full-thickness flap, exposed root surfaces were planed thoroughly. The 16 defects were assigned randomly to one of the following experimental conditions: CPC, CPC+EMD, EMD, and open flap debridement (OFD). Ten weeks post-surgery, the animals were sacrificed, and histologic specimens were prepared for histomorphometric evaluation. RESULTS: Defect sites treated with EMD only exhibited varying degrees of new cementum and new bone formation, whereas the OFD group presented only limited new cementum and bone formation. Defect sites where a CPC wall was implanted (CPC and CPC+EMD groups) revealed significantly greater regeneration of new bone and new cementum than in the EMD and OFD groups. No significant differences were observed between the CPC and CPC+EMD groups. CONCLUSIONS: CPC walls with and without EMD promoted regeneration of alveolar bone and cementum in 1-wall infrabony defects. Space and stable wound healing are believed to be crucial for periodontal regeneration in non-contained infrabony defects.

Injectable calcium phosphate bone cement provides favorable space and a scaffold for periodontal regeneration in dogs.

BACKGROUND: An earlier study showed that an injectable calcium phosphate cement (CPC) served as a stable scaffold for bone formation and promoted histocompatible healing of periodontal tissue in dogs. In this study, we evaluated the influence of CPC on regeneration of periodontal defects with experimental periodontitis in dogs. METHODS: Experimental periodontitis was induced by placing stainless-steel mesh on the mesial side of maxillary canines in six adult, healthy beagle dogs. Subsequently, intrabony defects were resized so as to be standard, and CPC was injected in the experimental bone defects. Non-grafted defects on the contralateral side served as controls. Twelve weeks after surgery, the animals were sacrificed and histologic specimens were prepared. Periodontal tissue healing was evaluated histologically and histometrically. RESULTS: Healing of periodontal tissues, in terms of bone and cementum formation, was consistently observed in the CPC-applied sites. CPC was partly replaced by new bone. New cementum and periodontal ligament-like tissue were observed between CPC and the root surface. New bone (P <0.05), new cementum (P <0.01), and new connective tissue attachment and adhesion (P <0.05) were significantly enhanced in the experimental sites. CONCLUSION: Calcium phosphate cement provides stable wound healing and enhanced periodontal regeneration in periodontal defects in dogs with experimental periodontitis.

Periodontal tissue healing following flap surgery using an Er:YAG laser in dogs.

BACKGROUND AND OBJECTIVES: The purpose of this study was to compare periodontal tissue healing following flap surgery using an Er:YAG laser with that of conventional surgery. STUDY DESIGN/MATERIALS AND METHODS: Bilateral premolars with experimentally induced periodontitis in six dogs were treated by periodontal flap surgery. Degranulation and root debridement in the furcation were performed using an Er:YAG laser or curet. At 3 months postsurgery, animals were sacrificed and decalcified specimens were prepared for histological and histometric analysis. RESULTS: Degranulation and root debridement were effectively performed with an Er:YAG laser without major thermal damage and significantly faster than with a curet. Histologically, the amount of newly formed bone was significantly greater in the laser group than in the curet group, although both groups showed similar amounts of cementum formation and connective tissue attachment. CONCLUSIONS: The Er:YAG laser irradiation can be safely and effectively utilized in periodontal flap surgery, and has the potential to promote new bone formation.