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1.
J Immunol ; 212(4): 663-676, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38149920

ABSTRACT

Implanted medical devices, from artificial heart valves and arthroscopic joints to implantable sensors, often induce a foreign body response (FBR), a form of chronic inflammation resulting from the inflammatory reaction to a persistent foreign stimulus. The FBR is characterized by a subset of multinucleated giant cells (MGCs) formed by macrophage fusion, the foreign body giant cells (FBGCs), accompanied by inflammatory cytokines, matrix deposition, and eventually deleterious fibrotic implant encapsulation. Despite efforts to improve biocompatibility, implant-induced FBR persists, compromising the utility of devices and making efforts to control the FBR imperative for long-term function. Controlling macrophage fusion in FBGC formation presents a logical target to prevent implant failure, but the actual contribution of FBGCs to FBR-induced damage is controversial. CD13 is a molecular scaffold, and in vitro induction of CD13KO bone marrow progenitors generates many more MGCs than the wild type, suggesting that CD13 regulates macrophage fusion. In the mesh implant model of FBR, CD13KO mice produced significantly more peri-implant FBGCs with enhanced TGF-ß expression and increased collagen deposition versus the wild type. Prior to fusion, increased protrusion and microprotrusion formation accompanies hyperfusion in the absence of CD13. Expression of fusogenic proteins driving cell-cell fusion was aberrantly sustained at high levels in CD13KO MGCs, which we show is due to a novel CD13 function, to our knowledge, regulating ubiquitin/proteasomal protein degradation. We propose CD13 as a physiologic brake limiting aberrant macrophage fusion and the FBR, and it may be a novel therapeutic target to improve the success of implanted medical devices. Furthermore, our data directly implicate FBGCs in the detrimental fibrosis that characterizes the FBR.


Subject(s)
Foreign Bodies , Foreign-Body Reaction , Mice , Animals , Foreign-Body Reaction/chemically induced , Foreign-Body Reaction/metabolism , Giant Cells, Foreign-Body/metabolism , Inflammation/metabolism , Foreign Bodies/metabolism , Prostheses and Implants/adverse effects , Ubiquitination
2.
Biomater Adv ; 155: 213669, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37980818

ABSTRACT

Pelvic Organ Prolapse (POP) is a common gynaecological disorder where pelvic organs protrude into the vagina. While transvaginal mesh surgery using non-degradable polymers was a commonly accepted treatment for POP, it has been associated with high rates of adverse events such as mesh erosion, exposure and inflammation due to serious foreign body response and therefore banned from clinical use after regulatory mandates. This study proposes a tissue engineering strategy using uterine endometrium-derived mesenchymal stem/stromal cells (eMSC) delivered with degradable poly L-lactic acid-co-poly ε-caprolactone (PLACL) and gelatin (G) in form of a composite electrospun nanofibrous mesh (P + G nanomesh) and evaluates the immunomodulatory mechanism at the material interfaces. The study highlights the critical acute and chronic inflammatory markers along with remodelling factors that determine the mesh surgery outcome. We hypothesise that such a bioengineered construct enhances mesh integration and mitigates the Foreign Body Response (FBR) at the host interface associated with mesh complications. Our results show that eMSC-based nanomesh significantly increased 7 genes associated with ECM synthesis and cell adhesion including, Itgb1, Itgb2, Vcam1, Cd44, Cdh2, Tgfb1, Tgfbr1, 6 genes related to angiogenesis including Ang1, Ang2, Vegfa, Pdgfa, Serpin1, Cxcl12, and 5 genes associated with collagen remodelling Col1a1, Col3a1, Col6a1, Col6a2, Col4a5 at six weeks post-implantation. Our findings suggest that cell-based tissue-engineered constructs potentially mitigate the FBR response elicited by biomaterial implants. From a clinical perspective, this construct provides an alternative to current inadequacies in surgical outcomes by modulating the immune response, inducing angiogenesis and ECM synthesis during the acute and chronic phases of the FBR.


Subject(s)
Foreign Bodies , Mesenchymal Stem Cells , Nanofibers , Female , Mice , Animals , Gelatin , Tissue Engineering/methods , Pelvic Floor , Mesenchymal Stem Cells/metabolism , Inflammation/metabolism , Foreign Bodies/metabolism , Regeneration
3.
Adv Healthc Mater ; 11(9): e2102209, 2022 05.
Article in English | MEDLINE | ID: mdl-34967497

ABSTRACT

Poly(ethylene glycol) (PEG) hydrogels hold promise for in vivo applications but induce a foreign body response (FBR). While macrophages are key in the FBR, many questions remain. This study investigates temporal changes in the transcriptome of implant-associated monocytes and macrophages. Proinflammatory pathways are upregulated in monocytes compared to control monocytes but subside by day 28. Macrophages are initially proinflammatory but shift to a profibrotic state by day 14, coinciding with fibrous capsule emergence. Next, this study assesses the origin of macrophages responsible for fibrous encapsulation using wildtype, C-C Motif Chemokine Receptor 2 (CCR2)-/- mice that lack recruited macrophages, and Macrophage Fas-Induced Apoptosis (MaFIA) mice that enable macrophage ablation. Subpopulations of recruited and tissue-resident macrophages are identified. Fibrous encapsulation proceeds in CCR2-/- mice similar to wildtype mice. However, studies in MaFIA mice indicate that macrophages are necessary for fibrous capsule formation. These findings suggest that macrophage origin impacts the FBR progression and provides evidence that tissue-resident macrophages and not the recruited macrophages may drive fibrosis in the FBR to PEG hydrogels. This study demonstrates that implant-associated monocytes and macrophages have temporally distinct transcriptomes in the FBR and that profibrotic pathways associated with macrophages may be enriched in tissue-resident macrophages.


Subject(s)
Foreign Bodies , Macrophage Activation , Animals , Biocompatible Materials/metabolism , Fibrosis , Foreign Bodies/metabolism , Hydrogels/metabolism , Hydrogels/pharmacology , Macrophages/metabolism , Mice , Mice, Inbred C57BL , Polyethylene Glycols/metabolism , Polyethylene Glycols/pharmacology
4.
Int Immunopharmacol ; 96: 107801, 2021 Jul.
Article in English | MEDLINE | ID: mdl-34162162

ABSTRACT

Cystatins are natural inhibitors of cysteine peptidases that are found practically in all living organisms. CaneCPI-5 is a sugarcane cystatin with inhibitory activity against human cathepsins B, K and L, which are cysteine proteases highly expressed in a variety of pathological conditions, usually marked by persistent inflammation and processing of the extracellular matrix. This work evaluated the effects of daily administration of the recombinant cystatin CaneCPI-5 [0.01, 0.1 or 1.0 µg in 10 µL of Phosphate-Buffered Saline (PBS)] on the inflammatory, angiogenic and fibrogenic components during chronic inflammatory response induced by subcutaneous sponge implants. The anti-inflammatory effect of treatment with CaneCPI-5 was confirmed by reduction of the levels of the pro-inflammatory mediators TNF-α, CXCL1 and CCL2/JE/MCP-1, as well as the activity of the myeloperoxidase and n-acetyl-ß-D-glucosaminidase. Treatment with CaneCPI-5 promoted angiogenesis in the implants, increasing the production of cytokines VEGF and FGF and the formation of new blood vessels. Finally, the administration of the recombinant cystatin favored the production of the pro-fibrogenic cytokine TGF-ß1 and collagen deposition next to the implants. Together, these results show the potential therapeutic application of CaneCPI-5 as an anti-inflammatory agent, capable of favoring angiogenesis and fibrogenesis processes, necessary for tissue repair.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Collagen/metabolism , Cystatins/therapeutic use , Foreign Bodies/drug therapy , Neovascularization, Physiologic/drug effects , Plant Proteins/therapeutic use , Animals , Anti-Inflammatory Agents/pharmacology , Cystatins/genetics , Cystatins/pharmacology , Cytokines/immunology , Disease Models, Animal , Down-Regulation/drug effects , Foreign Bodies/metabolism , Male , Mice, Inbred C57BL , Plant Proteins/genetics , Plant Proteins/pharmacology , Recombinant Proteins/pharmacology , Recombinant Proteins/therapeutic use , Saccharum , Skin/blood supply , Skin/drug effects , Skin/immunology , Skin/metabolism , Surgical Sponges
5.
Biomaterials ; 188: 144-159, 2019 01.
Article in English | MEDLINE | ID: mdl-30343257

ABSTRACT

The use of intracortical microelectrode arrays has gained significant attention in being able to help restore function in paralysis patients and study the brain in various neurological disorders. Electrode implantation in the cortex causes vasculature or blood-brain barrier (BBB) disruption and thus elicits a foreign body response (FBR) that results in chronic inflammation and may lead to poor electrode performance. In this study, a comprehensive insight into the acute molecular mechanisms occurring at the Utah electrode array-tissue interface is provided to understand the oxidative stress, neuroinflammation, and neurovascular unit (astrocytes, pericytes, and endothelial cells) disruption that occurs following microelectrode implantation. Quantitative real time polymerase chain reaction (qRT-PCR) was used to quantify the gene expression at acute time-points of 48-hr, 72-hr, and 7-days for factors mediating oxidative stress, inflammation, and BBB disruption in rats implanted with a non-functional 4 × 4 Utah array in the somatosensory cortex. During vascular disruption, free iron released into the brain parenchyma can exacerbate the FBR, leading to oxidative stress and thus further contributing to BBB degradation. To reduce the free iron released into the brain tissue, the effects of an iron chelator, deferoxamine mesylate (DFX), was also evaluated.


Subject(s)
Blood-Brain Barrier/pathology , Deferoxamine/therapeutic use , Electrodes, Implanted/adverse effects , Foreign Bodies/drug therapy , Foreign Bodies/etiology , Iron Chelating Agents/therapeutic use , Animals , Blood-Brain Barrier/drug effects , Blood-Brain Barrier/metabolism , Foreign Bodies/metabolism , Foreign Bodies/pathology , Inflammation/drug therapy , Inflammation/etiology , Inflammation/metabolism , Inflammation/pathology , Male , Oxidative Stress/drug effects , Rats, Sprague-Dawley
6.
Leg Med (Tokyo) ; 35: 9-11, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30227264

ABSTRACT

Postmortem computed tomography (PMCT) is becoming used more commonly in routine forensic investigation. CT is sensitive for detection of metal foreign bodies. Here we report a case of suicide due to self-ignition of kerosene that the victim had poured over herself. Prior to autopsy, PMCT detected tiny radiopaque particles arranged in a row in the surface of the back and either thigh, together with a series of similar particles under the skin lateral to the breasts or the bilateral inguinal region. At autopsy, external examination revealed third-degree burns involving charred tissues all over the body except for the head. Tattoos were visible on the back and on either thigh. The tattoos had colored designs, and the red portions corresponded to the radiopaque particles in the surface of the body. Internal examination demonstrated swelling of the axillary and inguinal lymph nodes, which corresponded to the radiopaque particles. A wave length-dispersive X-ray spectroscopy revealed deposition of mercury and titanium in the inguinal lymph nodes. Thus, it was plausible that the ink could have contributed to the radiopaque particles found by PMCT in the surface of the back and thighs, as well in the lymph nodes. The present case was able to provide clues for interpretation of radiopaque particles revealed by PMCT in the surface of the body.


Subject(s)
Foreign Bodies/diagnostic imaging , Foreign Bodies/metabolism , Forensic Medicine/methods , Mercury Compounds/metabolism , Postmortem Changes , Tattooing , Titanium/metabolism , Tomography, X-Ray Computed , Female , Humans , Ink , Lymph Nodes/diagnostic imaging , Lymph Nodes/metabolism , Middle Aged , Skin/diagnostic imaging , Skin/metabolism , Suicide
7.
Drug Deliv ; 25(1): 1147-1160, 2018 Nov.
Article in English | MEDLINE | ID: mdl-29781340

ABSTRACT

The combination of protein-coated graphene oxide (GO) and microencapsulation technology has moved a step forward in the challenge of improving long-term alginate encapsulated cell survival and sustainable therapeutic protein release, bringing closer its translation from bench to the clinic. Although this new approach in cell microencapsulation represents a great promise for long-term drug delivery, previous studies have been performed only with encapsulated murine C2C12 myoblasts genetically engineered to secrete murine erythropoietin (C2C12-EPO) within 160 µm diameter hybrid alginate protein-coated GO microcapsules implanted into syngeneic mice. Here, we show that encapsulated C2C12-EPO myoblasts survive longer and release more therapeutic protein by doubling the micron diameter of hybrid alginate-protein-coated GO microcapsules to 380 µm range. Encapsulated mesenchymal stem cells (MSC) genetically modified to secrete erythropoietin (D1-MSCs-EPO) within 380 µm-diameter hybrid alginate-protein-coated GO microcapsules confirmed this improvement in survival and sustained protein release in vitro. This improved behavior is reflected in the hematocrit increase of allogeneic mice implanted with both encapsulated cell types within 380 µm diameter hybrid alginate-protein-coated GO microcapsules, showing lower immune response with encapsulated MSCs. These results provide a new relevant step for the future clinical application of protein-coated GO on cell microencapsulation.


Subject(s)
Alginates/chemistry , Alginates/pharmacology , Capsules/chemistry , Cell Survival/drug effects , Foreign Bodies/drug therapy , Graphite/chemistry , Oxides/chemistry , Animals , Capsules/pharmacology , Cell Line , Delayed-Action Preparations/chemistry , Delayed-Action Preparations/pharmacology , Drug Compounding/methods , Drug Delivery Systems/methods , Erythropoietin/metabolism , Foreign Bodies/metabolism , Glucuronic Acid/chemistry , Glucuronic Acid/pharmacology , Hematocrit/methods , Hexuronic Acids/chemistry , Hexuronic Acids/pharmacology , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/metabolism , Mice , Myoblasts/drug effects , Myoblasts/metabolism
9.
Bone Joint J ; 98-B(12): 1662-1667, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27909129

ABSTRACT

AIMS: We present a case series of five patients who had revision surgery following magnetic controlled growing rods (MGCR) for early onset scoliosis. Metallosis was found during revision in four out of five patients and we postulated a mechanism for rod failure based on retrieval analysis. PATIENTS AND METHODS: Retrieval analysis was performed on the seven explanted rods. The mean duration of MCGR from implantation to revision was 35 months (17 to 46). The mean age at revision was 12 years (7 to 15; four boys, one girl). RESULTS: A total of six out of seven rods had tissue metallosis and pseudo-capsule surrounding the actuator. A total of four out of seven rods were pistoning. There were two rods which were broken. All rods had abrasive circumferential markings. A significant amount of metal debris was found when the actuators were carefully cut open. Analytical electron microscopy demonstrated metal fragments of predominantly titanium with a mean particle size of 3.36 microns (1.31 to 6.61). CONCLUSION: This study highlights concerns with tissue metallosis in MCGR. We recommend careful follow-up of patients who have received this implant. Cite this article: Bone Joint J 2016;98-B:1662-7.


Subject(s)
Bone Nails/adverse effects , Foreign Bodies/etiology , Scoliosis/surgery , Child , Child, Preschool , Device Removal , Female , Follow-Up Studies , Foreign Bodies/metabolism , Foreign Bodies/pathology , Humans , Magnetics , Male , Prosthesis Design , Prosthesis Failure , Reoperation/methods , Titanium/analysis
10.
BMC Bioinformatics ; 17: 111, 2016 Feb 29.
Article in English | MEDLINE | ID: mdl-26927968

ABSTRACT

BACKGROUND: Computational modeling and simulation play an important role in analyzing the behavior of complex biological systems in response to the implantation of biomedical devices. Quantitative computational modeling discloses the nature of foreign body responses. Such understanding will shed insight on the cause of foreign body responses, which will lead to improved biomaterial design and will reduce foreign body reactions. One of the major obstacles in computational modeling is to build a mathematical model that represents the biological system and to quantitatively define the model parameters. RESULTS: In this paper, we considered quantitative inter connections and logical relationships among diverse proteins and cells, which have been reported in biological experiments and literature. Based on the established biological discovery, we have built a mathematical model while unveiling the key components that contribute to biomaterial-mediated inflammatory responses. For the parameter estimation of the mathematical model, we proposed a global optimization algorithm, called Discrete Selection Levenberg-Marquardt (DSLM). This is an extension of Levenberg-Marquardt (LM) algorithm which is a gradient-based local optimization algorithm. The proposed DSLM suggests a new approach for the selection of optimal parameters in the discrete space with fast computational convergence. CONCLUSIONS: The computational modeling not only provides critical clues to recognize current knowledge of fibrosis development but also enables the prediction of yet-to-be observed biological phenomena.


Subject(s)
Algorithms , Biocompatible Materials/administration & dosage , Cell Movement , Computer Simulation , Foreign Bodies/immunology , Foreign-Body Reaction/immunology , Phagocytes/physiology , Animals , Foreign Bodies/metabolism , Implants, Experimental , Mice , Subcutaneous Tissue/immunology
11.
Sci Rep ; 6: 20635, 2016 Feb 10.
Article in English | MEDLINE | ID: mdl-26860464

ABSTRACT

Detailing the inflammatory mechanisms of biomaterial-implant induced foreign body responses (FBR) has implications for revealing targetable pathways that may reduce leukocyte activation and fibrotic encapsulation of the implant. We have adapted a model of poly(methylmethacrylate) (PMMA) bead injection to perform an assessment of the mechanistic role of the ASC-dependent inflammasome in this process. We first demonstrate that ASC(-/-) mice subjected to PMMA bead injections had reduced cell infiltration and altered collagen deposition, suggesting a role for the inflammasome in the FBR. We next investigated the NLRP3 and AIM2 sensors because of their known contributions in recognising damaged and apoptotic cells. We found that NLRP3 was dispensable for the fibrotic encapsulation; however AIM2 expression influenced leukocyte infiltration and controlled collagen deposition, suggesting a previously unexplored link between AIM2 and biomaterial-induced FBR.


Subject(s)
Apoptosis Regulatory Proteins/genetics , Biocompatible Materials/pharmacology , DNA-Binding Proteins/metabolism , Foreign Bodies/pathology , Immunity, Innate/drug effects , Inflammasomes/metabolism , Acute Disease , Adsorption , Animals , Apoptosis Regulatory Proteins/deficiency , Biocompatible Materials/chemistry , Blood Proteins/chemistry , Blood Proteins/metabolism , CARD Signaling Adaptor Proteins , Collagen Type I/metabolism , Collagen Type II/metabolism , Cytokines/analysis , DNA-Binding Proteins/deficiency , DNA-Binding Proteins/genetics , Enzyme-Linked Immunosorbent Assay , Foreign Bodies/immunology , Foreign Bodies/metabolism , Immunophenotyping , Macrophages/cytology , Macrophages/immunology , Macrophages/metabolism , Mice , Mice, Inbred C57BL , Mice, Knockout , Microscopy, Fluorescence , NLR Family, Pyrin Domain-Containing 3 Protein/deficiency , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Neutrophils/cytology , Neutrophils/immunology , Neutrophils/metabolism , Peritoneal Lavage , Polymethyl Methacrylate/chemistry , Polymethyl Methacrylate/pharmacology , Prostheses and Implants
12.
Int J Oral Maxillofac Implants ; 30(5): 1168-73, 2015.
Article in English | MEDLINE | ID: mdl-26394356

ABSTRACT

PURPOSE: Peri-implantitis is a disease characterized by soft tissue inflammation and continued loss of supporting bone, which can result in implant failure. Peri-implantitis is a multifactorial disease, and one of its triggering factors may be the presence of excess cement in the soft tissues surrounding an implant. This descriptive study evaluated the composition of foreign particles from 36 human biopsy specimens with 19 specimens selected for analysis. The biopsy specimens were obtained from soft tissues affected by peri-implantitis around cement-retained implant crowns and compared with the elemental composition of commercial luting cement. MATERIALS AND METHODS: Nineteen biopsy specimens were chosen for the comparison, and five test cements (TempBond, Telio, Premier Implant Cement, Intermediate Restorative Material, and Relyx) were analyzed using scanning electron microscopy equipped with energy dispersive x-ray spectroscopy. This enabled the identification of the chemical composition of foreign particles embedded in the tissue specimens and the composition of the five cements. Statistical analysis was conducted using classification trees to pair the particles present in each specimen with the known cements. RESULTS: The particles in each biopsy specimen could be associated with one of the commercial cements with a level of probability ranging between .79 and 1. TempBond particles were found in one biopsy specimen, Telio particles in seven, Premier Implant Cement particles in four, Relyx particles in four, and Intermediate Restorative Material particles in three. CONCLUSION: Particles found in human soft tissue biopsy specimens around implants affected by peri-implant disease were associated with five commercially available dental cements.


Subject(s)
Dental Cements/chemistry , Peri-Implantitis/pathology , Aluminum/analysis , Biopsy/methods , Crowns , Dental Materials/chemistry , Dental Prosthesis Retention , Dental Prosthesis, Implant-Supported , Eugenol/chemistry , Foreign Bodies/metabolism , Foreign Bodies/pathology , Humans , Methylmethacrylates/chemistry , Microscopy, Electron, Scanning , Resin Cements/chemistry , Retrospective Studies , Silicon/analysis , Spectrometry, X-Ray Emission , Zinc/analysis , Zinc Oxide/chemistry , Zinc Oxide-Eugenol Cement/chemistry , Zirconium/analysis
13.
Mol Med Rep ; 9(3): 872-6, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24378398

ABSTRACT

The foreign body response (FBR) is described as the host's response to implanted biomaterials, which involves a complex cascade of immune modulators. The dynamic changes of immune cells, inflammatory cytokines and the formation of a fibrous capsule remain to be elucidated. In the present study, a model of subcutaneous implantation of a tissue expander was used. The results revealed that macrophages, the main immune cells in FBR, infiltrated into the expanded tissue and located at the tissue­material interface from day 1­90. Following the decrease of the number of macrophages, collagen deposited and fibroblasts transformed into myofibroblasts at the tissue­material interface, leading to the formation of a fibrous capsule from day 14. The persistent existing macrophages led to a high expression of proinflammatory cytokines, including tumor necrosis factor­α and interleukin­1ß, both of which initiated the NK-κB and JNK inflammatory pathways, mediating the FBR to tissue expander implantation.


Subject(s)
Foreign Bodies/immunology , Tissue Expansion Devices/adverse effects , Animals , Biocompatible Materials/pharmacology , Collagen/metabolism , Cytokines/metabolism , Foreign Bodies/metabolism , Foreign Bodies/pathology , Injections, Subcutaneous , Interleukin-1beta/metabolism , JNK Mitogen-Activated Protein Kinases/metabolism , Macrophages/drug effects , Macrophages/immunology , Macrophages/metabolism , Male , Myofibroblasts/cytology , NF-kappa B/metabolism , Prostheses and Implants , Rats , Rats, Inbred Lew , Skin/pathology , Tumor Necrosis Factor-alpha/metabolism , Up-Regulation/drug effects , p38 Mitogen-Activated Protein Kinases/metabolism
14.
Top Companion Anim Med ; 28(1): 28-31, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23796486

ABSTRACT

Polyurethane adhesives are found in a large number of household products in the United States and are used for a variety of purposes. Several brands of these expanding wood glues (those containing diphenylmethane diisocyanate [MDI]) have the potential to form gastrointestinal (GI) foreign bodies if ingested. The ingested adhesive forms an expanding ball of glue in the esophagus and gastric lumen. This expansion is caused by a polymerization reaction using the heat, water, and gastric acids of the stomach. A firm mass is created that can be 4-8 times its original volume. As little as 2 oz of glue have been reported to develop gastric foreign bodies. The obstructive mass is reported to form within minutes of ingestion of the adhesive. The foreign body can lead to esophageal impaction and obstruction, airway obstruction, gastric outflow obstruction, mucosal hemorrhage, ulceration, laceration, perforation of the esophageal and gastric linings, and death. Clinical signs following ingestion include anorexia, lethargy, vomiting, tachypnea, and abdominal distention and pain, and typically develop within 12 hours. Clinical signs may depend upon the size of the mass. If left untreated, perforation and rupture of the esophagus or stomach can occur. The glue mass does not stick to the GI mucosa and is not always detectable on abdominal palpation. Radiographs are recommended to confirm the presence of the "glue-ball" foreign body, and radiographic evidence of the obstruction may be seen as early as 4-6 hours following ingestion. Emesis is contraindicated owing to the risk of aspiration of the glue into the respiratory tree or the subsequent lodging of the expanding glue mass in the esophagus. Likewise, efforts to dilute the glue and prevent the formation of the foreign body through administration of liquids, activated charcoal, or bulk-forming products to push the foreign body through the GI tract have proven ineffective. Even endoscopy performed to remove the foreign body has been shown to be unreliable. The safest, most effective, and successful therapy is surgical intervention to remove the GI foreign body. If performed early enough, complete recovery of the animal can be expected. Differential diagnoses for polyurethane adhesive ingestion include any potential cause of GI obstruction. The public is largely unaware of the hazards that ingestion of this product may produce. Public education efforts are needed to inform pet owners about the hazards of these glues and the overall importance of providing our companion animals with safe, poison-free environments.


Subject(s)
Adhesives/poisoning , Dog Diseases/chemically induced , Foreign Bodies/veterinary , Pets , Polyurethanes/poisoning , Animals , Dogs , Foreign Bodies/metabolism , Foreign Bodies/therapy , Prognosis
15.
Acta Biomater ; 9(5): 6502-10, 2013 May.
Article in English | MEDLINE | ID: mdl-23376130

ABSTRACT

Implantation of biomaterials into the body elicits a material-dependent inflammatory response called the foreign body reaction (FBR). Macrophages play a pivotal role in the FBR by orchestrating the pro-inflammatory microenvironment around the biomaterials by secreting cytokines, chemokines and growth factors. When the biomaterial is porous or degradable, macrophages can migrate into the material and continue the generation of a pro-inflammatory microenvironment inside the materials. They also regulate the degradation of biomaterials by secreting proteolytic enzymes and by phagocytosis. We hypothesize that macrophages present in the different microenvironments of the FBR have different phenotypes. Fundamental knowledge of the phenotypes of macrophages and their dynamics during the FBR will contribute to our overall understanding of the mechanisms involved in the FBR, and may provide us with additional tools to modulate the FBR. To investigate the phenotype of macrophages in the FBR, we validated phenotype-specific markers for rat macrophages in vitro by stimulating them with IFNγ/LPS, IL4/IL13 or IL4/dexamethasone to induce classically activated macrophages (M1φ) or alternatively activated macrophages (M2φ). Gene expression analysis, Western blot and immunohistochemistry revealed that iNOS and CD206 are specifically expressed by M1φ and M2φ, respectively. Using these markers, we investigated the distribution of M1φ and M2φ in the FBR induced by subcutaneously implanted hexamethylenediisocyanate cross-linked dermal sheep collagen (HDSC) disks in AO rats. We found that part of the macrophages display an M2 phenotype, whereas the M1phenotype was not detected. Our data suggest that many macrophages in the FBR induced by HDSC do not fit into the classical M1 or M2 dichotomy.


Subject(s)
Collagen/metabolism , Foreign Bodies/metabolism , Macrophages/metabolism , Animals , Base Sequence , Blotting, Western , DNA Primers , Immunohistochemistry , Male , Phenotype , Polymerase Chain Reaction , Rats
16.
Clin Hemorheol Microcirc ; 53(1-2): 97-115, 2013.
Article in English | MEDLINE | ID: mdl-22954639

ABSTRACT

Cardiovascular implants are increasingly important in regenerative medicine. To improve the safety and function of blood-contacting implants a major need exists for new polymer-based biomaterials that avoid adverse reactions, particularly thrombotic events. This review is aimed to summarize the multi-stepped and interlinked processes leading to a thrombus growth on body foreign surfaces: protein adsorption, platelet adhesion accompanied by activation and spreading and the release of substances of various organelles activating other neighboured platelets (and the plasmatic coagulation) leading to the formation of a plug of platelets and, finally, to a thrombus.


Subject(s)
Biocompatible Materials , Blood Platelets/metabolism , Materials Testing/methods , Adsorption , Foreign Bodies/metabolism , Humans , Platelet Activation , Platelet Adhesiveness , Prostheses and Implants/adverse effects , Surface Properties , Thrombosis/etiology , Thrombosis/prevention & control
17.
Am J Rhinol Allergy ; 26(3): 233-6, 2012.
Article in English | MEDLINE | ID: mdl-22643952

ABSTRACT

BACKGROUND: Penetrating trauma to the paranasal sinuses and skull base with retained foreign bodies represents a unique challenge for head and neck surgeons. Management of these injuries is complicated by associated injuries and the proximity to vital neurovascular structures. This study was designed to review the clinical experience with retained sinonasal and skull base projectile foreign bodies at a single academic tertiary care institution. METHODS: A retrospective review of patients who suffered penetrating trauma to the head with retained metallic foreign bodies in the paranasal sinuses and/or skull base between January 2002 and August 2011 was performed at a single academic medical center. RESULTS: There were 599 patients who suffered penetrating trauma to the head and neck, with 13 patients having retained metallic foreign bodies in the sinuses and/or skull base, mostly bullets or nails. Ten patients underwent urgent (n = 5) or delayed (n = 5) removal of foreign bodies accessible without compromise of adjacent structures either through an endoscopic or open approach. Three patients had multiple foreign bodies that were not removed. Three patients experienced traumatic cerebrospinal fluid fistula managed with either conservative measures (n = 2) or intraoperative repair at the time of foreign body retrieval (n = 1). All patients received prophylactic antibiotic coverage. No patients suffered infectious complications such as sinusitis from retained foreign bodies. CONCLUSION: Although not all retained foreign bodies after penetrating trauma to the head require removal, those that are safely accessible and at risk for infectious complications should be recovered. The timing and approach of retrieval are dictated by the clinical scenario.


Subject(s)
Foreign Bodies/surgery , Head Injuries, Penetrating/surgery , Paranasal Sinuses/surgery , Adolescent , Adult , Algorithms , Disease Management , Female , Foreign Bodies/metabolism , Head Injuries, Penetrating/physiopathology , Humans , Male , Middle Aged , Paranasal Sinuses/diagnostic imaging , Paranasal Sinuses/injuries , Paranasal Sinuses/metabolism , Retrospective Studies , Tomography, X-Ray Computed , Young Adult
18.
J Anesth ; 26(5): 796-7, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22644358

ABSTRACT

Accidental ingestion of a foreign body into either tracheobronchial tree or esophagus is not an uncommon occurrence. However, there is limited literature available on sequelae of post foreign body ingestion--carbon dioxide set point and apneic threshold due to chronic respiratory acidosis. We report a case of chronic airway obstruction in a 14-month-old boy with prior history of battery ingestion and share our experience in the management.


Subject(s)
Anesthetics/administration & dosage , Carbon Dioxide/metabolism , Pulmonary Disease, Chronic Obstructive/metabolism , Pulmonary Disease, Chronic Obstructive/surgery , Foreign Bodies/metabolism , Humans , Infant , Male , Tracheostomy/methods
19.
Arch Gynecol Obstet ; 284(3): 713-9, 2011 Sep.
Article in English | MEDLINE | ID: mdl-20949357

ABSTRACT

OBJECTIVE: This study aims to review cases of extra-ovarian conditions that resembled ovarian malignancy and thus, to evaluate the distribution of primary pathology mimicking ovarian malignancy. METHODS: A retrospective review of women, with final pathology of extra-ovarian diseases mimicking ovarian malignancy, which were managed at Zekai Tahir Burak Women's Health Education and Research Hospital, from January 1995 to April 2010 was undertaken. RESULTS: Among the 2,210 women treated during the study period, extra-ovarian diseases accounted for 5.11% (113/2,210) of all the cases. Of the 113 extra-ovarian diseases, 42 (37.17%) were peritoneal tuberculosis, 25 (22.13%) were gastrointestinal malignancies, 20 (17.70%) were pelvic abscess, 8 (7.08%) were pelvic echinococcosis, 8 (7.08) were schwannoma and other retroperitoneal tumors, 4 (3.53%) were malignant lymphoma, 2 (1.77%) were chronic ectopic pregnancy, gossypiboma, and mesenteric cyst, respectively. CONCLUSION: Medical awareness of infectious diseases such as peritoneal tuberculosis, pelvic abscess, and pelvic echinococcosis in the differential diagnosis of ovarian malignancy is still lacking, especially in developing countries. In addition, in case of a pelvic mass, gastrointestinal and retroperitoneal tumors and malignant lymphoma should always be considered to avoid pitfalls in diagnosis and therapy.


Subject(s)
Gastrointestinal Neoplasms/diagnosis , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/metabolism , Retroperitoneal Neoplasms/diagnosis , Abscess/diagnosis , Abscess/metabolism , Adenocarcinoma/diagnosis , Adenocarcinoma/metabolism , Adolescent , Adult , Aged , CA-125 Antigen/metabolism , Diagnosis, Differential , Echinococcosis/diagnosis , Echinococcosis/metabolism , Female , Foreign Bodies/diagnosis , Foreign Bodies/metabolism , Gastrointestinal Neoplasms/metabolism , Humans , Lymphoma/diagnosis , Lymphoma/metabolism , Mesenteric Cyst/diagnosis , Mesenteric Cyst/metabolism , Middle Aged , Neurilemmoma/diagnosis , Neurilemmoma/metabolism , Pelvis , Peritonitis, Tuberculous/diagnosis , Peritonitis, Tuberculous/metabolism , Pregnancy , Pregnancy, Ectopic/diagnosis , Pregnancy, Ectopic/metabolism , Retroperitoneal Neoplasms/metabolism , Retrospective Studies , Young Adult
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