Search results for: bone marrow macrophages
660 Numerical Simulation of Bio-Chemical Diffusion in Bone Scaffolds
Authors: Masoud Madadelahi, Amir Shamloo, Seyedeh Sara Salehi
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Previously, some materials like solid metals and their alloys have been used as implants in human’s body. In order to amend fixation of these artificial hard human tissues, some porous structures have been introduced. In this way, tissues in vicinity of the porous structure can be attached more easily to the inserted implant. In particular, the porous bone scaffolds are useful since they can deliver important biomolecules like growth factors and proteins. This study focuses on the properties of the degradable porous hard tissues using a three-dimensional numerical Finite Element Method (FEM). The most important studied properties of these structures are diffusivity flux and concentration of different species like glucose, oxygen, and lactate. The process of cells migration into the scaffold is considered as a diffusion process, and related parameters are studied for different values of production/consumption rates.Keywords: bone scaffolds, diffusivity, numerical simulation, tissue engineering
Procedia PDF Downloads 385659 The Aminoguanidine Reduced NO Synthase Activity and Infiltration of Macrophages in Inflammation Induced by LPS in Rats
Authors: Hakim Chayeb
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Macrophages (Mo) play an essential role in host defense against pathogens. These inflammatory cells contain a large group of inducible enzymes such as NO synthase (NOS). This study was conducted to characterize experimentally induced inflammation in vivo by lipopolysaccharides (LPS). LPS is an essential component of the outer membrane of Gram-negative bacteria and a potent inducer of macrophage. Except control rats, all rats received different doses of LPS intra-peritoneally. The involvement of inducible NO synthase (iNOS) and constitutive (cNOS ) in the modulation of the inflammatory response was studied by treating the rats with L-NAME (non-selective NOS inhibitor) or aminoguanidine (AG inhibitor of iNOS). Inhibitors were injected 24 hours before LPS administration. The results showed that esterase activity (a marker of macrophage infiltration) which is induced by LPS is reduced by AG, was potentiated by treatment with L-NAME in tissue homogenates of the liver, kidney and spleen. Meanwhile, the concentrations of nitric oxide (NO) induced by LPS were reduced with AG and are completely inhibited with L-NAME in the tissues studied. NO concentrations and plasma transaminase levels have undergone remarkable increases in rats treated with LPS alone. However, the AG significantly reduced these rates. Our results highlighted the role of NO synthase inhibitors in reducing of inflammatory responses that characterize many infectious diseases.Keywords: aminoguanidine, esterase, LPS, L-NAME, macrophage, nitric oxide
Procedia PDF Downloads 259658 Stem Cell Fate Decision Depending on TiO2 Nanotubular Geometry
Authors: Jung Park, Anca Mazare, Klaus Von Der Mark, Patrik Schmuki
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In clinical application of TiO2 implants on tooth and hip replacement, migration, adhesion and differentiation of neighboring mesenchymal stem cells onto implant surfaces are critical steps for successful bone regeneration. In a recent decade, accumulated attention has been paid on nanoscale electrochemical surface modifications on TiO2 layer for improving bone-TiO2 surface integration. We generated, on titanium surfaces, self-assembled layers of vertically oriented TiO2 nanotubes with defined diameters between 15 and 100 nm and here we show that mesenchymal stem cells finely sense TiO2 nanotubular geometry and quickly decide their cell fate either to differentiation into osteoblasts or to programmed cell death (apoptosis) on TiO2 nanotube layers. These cell fate decisions are critically dependent on nanotube size differences (15-100nm in diameters) of TiO2 nanotubes sensing by integrin clustering. We further demonstrate that nanoscale topography-sensing is feasible not only in mesenchymal stem cells but rather seems as generalized nanoscale microenvironment-cell interaction mechanism in several cell types composing bone tissue network including osteoblasts, osteoclast, endothelial cells and hematopoietic stem cells. Additionally we discuss the synergistic effect of simultaneous stimulation by nanotube-bound growth factor and nanoscale topographic cues on enhanced bone regeneration.Keywords: TiO2 nanotube, stem cell fate decision, nano-scale microenvironment, bone regeneration
Procedia PDF Downloads 432657 Study and Analyze of Metallic Glasses for Biomedical Applications: From Soft to Bone Tissue Engineering
Authors: A. Monfared, S. Faghihi
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Metallic glasses (MGs) are newcomers in the field of metals that show great potential for soft and bone tissue engineering due to the amorphous structure that endows unique properties. Up to now, various MGs based on Ti, Zr, Mg, Zn, Fe, Ca, and Sr in the form of a ribbon, bulk, thin-film, and powder have been investigated for biomedical purposes. This article reviews the compositions and biomedical properties of MGs as well as analyzes results in order to guide new approaches and future development of MGs.Keywords: metallic glasses, biomaterials, biocompatibility, biocorrosion
Procedia PDF Downloads 213656 Cryptosporidium Parvum oocytic Antigen Induced a Pro-Inflammatory DC Phenotype
Authors: Connick K, Lalor R, Murphy A, O’Neill S. M., Rabab S. Zalat, Eman E. El Shanawany
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Cryptosporidium parvum is an opportunistic intracellular parasite that causes mild to severe diarrhea in human and animal populations and is an important zoonotic disease globally. In immunocompromised hosts, infection Canbe life-threatening as no effective treatments are currently available to control infection. To increase our understanding of the mechanisms that play a role in host-parasite interactions at the level of the immune response, we investigated the effects of Cryptosporidium parvum antigen (CPA) on bone marrow-derived (DCS). Herein we examined cytokine secretion and cell surface marker expression on DCs exposed to CPA. We also measured cytokine production in CD4+ cells co-cultured with CPA primed DCs in the presence of anti-CD3. CPA induced a significant increase in the production of interleukin(IL)-12p40, IL-10, IL-6, and TNF-α by DCs and enhanced the expression of the cell surface markers TLR4, CD80, CD86, and MHC11. CPA primed DC co-cultured in the presence of anti-CD3 with CD4+ T-cells inhibited the secretion of Th2 associated cytokines, notably IL-5 and IL-13, with no effects on the secretions of interferon (IFN)-γ, IL-2, IL-17, and IL-10. These findings support studies in the literature that CPA can induce the full maturation of DCs that subsequently initiate Th1 immune responses critical to the resolution of C. parvum infection.Keywords: cryptosporidium parvum, dendritic cells, IL-12 p70, cell surface marker
Procedia PDF Downloads 173655 The Prognostic Values of Current Staging Schemes in Temporal Bone Carcinoma: A Real-World Evidence-Based Study
Authors: Minzi Mao, Jianjun Ren, Yu Zhao
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Objectives: The absence of a uniform staging scheme for temporal bone carcinoma (TBC) seriously impedes the improvement of its management strategies. Therefore, this research was aimed to investigate the prognostic values of two currently applying staging schemes, namely, the modified Pittsburgh staging system (MPB) and Stell’s T classification (Stell-T) in patients with TBC. Methods: Areal-world single-institution retrospectivereview of patientsdiagnosed with TBC between2008 and 2019 was performed. Baseline characteristics were extracted, and patients were retrospectively staged by both the MPB and Stell-T classifications. Cox regression analyseswereconductedtocomparetheoverall survival (OS). Results: A total of 69 consecutive TBC patients were included in thisstudy. Univariate analysis showed that both Stell-T and T- classifications of the modified Pittsburgh staging system (MPB-T) were significant prognostic factors for all TBC patients as well as temporal bone squamous cell carcinoma (TBSCC, n=50) patients (P < 0.05). However, only Stell-T was confirmed to be an independent prognostic factor in TBSCC patients (P = 0.004). Conclusions: Tumor extensions, quantified by both Stell-T and MPB-T classifications, are significant prognostic factors for TBC patients, especially for TBSCC patients. However, only the Stell-T classification is an independent prognostic factor for TBSCC patients.Keywords: modified pittsburgh staging system, overall survival, prognostic factor, stell’s T- classification, temporal bone carcinoma
Procedia PDF Downloads 129654 The Long-Term Effects of Immediate Implantation, Early Implantation and Delayed Implantation at Aesthetics Area
Authors: Xing Wang, Lin Feng, Xuan Zou, Hongchen liu
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Immediate Implantation after tooth extraction is considered to be the ideal way to retain the alveolar bone, but some scholars believe the aesthetic effect in the Early Implantation case are more reliable. In this study, 89 patients were added to this retrospective study up to 5 years. Assessment indicators was including the survival of the implant (peri-implant infection, implant loosening, shedding, crowns and occlusal), aesthetics (color and fullness gums, papilla height, probing depth, X-ray alveolar crest height, the patient's own aesthetic satisfaction, doctors aesthetics score), repair defects around the implant (peri-implant bone changes in height and thickness, whether the use of autologous bone graft, whether to use absorption/repair manual nonabsorbable material), treatment time, cost and the use of antibiotics.The results demonstrated that there is no significant difference in long-term success rate of immediate implantation, early implantation and delayed implantation (p> 0.05). But the results indicated immediate implantation group could get get better aesthetic results after two years (p< 0.05), but may increase the risk of complications and failures (p< 0.05). High-risk indicators include gingival recession, labial bone wall damage, thin gingival biotypes, planting position and occlusal restoration bad and so on. No matter which type of implanting methods was selected, the extraction methods and bone defect amplification techniques are observed as a significant factors on aesthetic effect (p< 0.05).Keywords: immediate implantation, long-term effects, aesthetics area, dental implants
Procedia PDF Downloads 356653 Case Report: Clinical Improvement of Forbrain Neurologic Signs in 3- Month- Old Persian Mastiff Dog with Calvarial Hyperostosis Syndrome after Corticosteroid, Antiepileptic and Antibiotic Therapy
Authors: Hamidreza Jahani, Zahra Salehzadeh, Ehsan Amini, Mohsen Tohidifar
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Calvarial Hyperostosis Syndrome (CHS) is a benign bone disease of the skull. It is a non-neoplastic and proliferative bone disease, and the main feature of the disease is progressive and asymmetrical bone involvement. CHS is mostly reported in young male and female bullmastiff dogs and less frequently in other breeds. The etiology of CHS is unknown. This is the first case report of CHS in Iran. A 3-month-old male Persian Mastiff was presented with chief complaints of multiple episodes of seizure, pacing, bizarre behavior, delayed growth, head pressing, and difficulty in opening the mouth. Central blindness and open fontanelles were observed in clinical examination. No abnormality was found in the complete blood count and routine blood biochemical tests. CT scan findings include cortical thickening of frontal and parietal bones and enlargement of the left retropharyngeal lymph node. For treatment, oral clindamycin for two weeks, prednisolone and phenobarbital for one month, respectively, were administrated, and the case showed improvement after a week and recovered after one month.Keywords: calvarial hyperostosis, Persian Mastiff, frontal bone, seizure
Procedia PDF Downloads 137652 Preparation and Characterization of Poly (ε-caprolactone) Loaded with Layered Double Hydroxide Nanohybrid Intercalated with Alendronate for Osteoporosis Treatment
Authors: Seyedeh Faranak Baniahmad, Soroor Yousefi
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Osteoporosis is a bone disease which increases the bone fracture risk, reduces the bone mineral density (BMD) and alters the amount and variety of proteins in bones. Antiresorptive therapy is one the most popular Osteoporosis treatment methods. In this method the bisphosphonates, hormones, calcitonin or the selective estrogen receptor modulators is replaced. In order to reduce undesirable effects and to increase the bioavailability of drug agents, the controlled drug delivery systems have been utilized. In current study, the controlled release of Alendronate from LDH-PCL with (0, 5, 10, 15 % wt. of LDH) was investigated. The results showed that the release of alendronate from the lamellar LDH incorporated into the PCL matrix is much slower than the release of alendronate from the PCL. Therefore such systems are very promising, in which the antiresorptive drug has to remain in the matrix for longer time and can be released in controlled manner.Keywords: osteoporosis, alendronate, poly (ε–caprolactone), layered double hydroxide
Procedia PDF Downloads 394651 Static and Dynamic Load on Hip Contact of Hip Prosthesis and Thai Femoral Bones
Authors: K. Chalernpon, P. Aroonjarattham, K. Aroonjarattham
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Total hip replacement had been one of the most successful operations in hip arthritis surgery. The purpose of this research had been to develop a dynamic hip contact of Thai femoral bone to analyze the stress distribution on the implant and the strain distribution on the bone model under daily activities and compared with the static load simulation. The results showed the different of maximum von Mises stress 0.14 percent under walking and 0.03 percent under climbing stair condition and the different of equivalent total strain 0.52 percent under walking and 0.05 percent under climbing stair condition. The muscular forces should be evaluated with dynamic condition to reduce the maximum von Mises stress and equivalent total strain.Keywords: dynamic loading, static load, hip prosthesis, Thai femur, femoral bone, finite element analysis
Procedia PDF Downloads 349650 Morphometric and Radiographic Studies on the Tarsal Bones of Adult Chinkara (Gazella bennettii)
Authors: Salahud Din, Saima Masood, Hafsa Zaneb, Habib-Ur Rehman, Imad Khan, Muqader Shah
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The present study was carried out on the gross anatomy, biometery and radiographic analysis of tarsal bones in twenty specimens of adult chinkara (Gazella bennettii). The desired bones were collected from the graveyards present in the locality of the different safari parks and zoos in Pakistan. To observe the edges and articulations between the bones, the radiographic images were acquired in craniocaudals and mediolateral views of the intact limbs. The gross and radiographic studies of the tarsus of adult Chinkara were carried out in University of Veterinary and Animal Sciences, Lahore, Pakistan. The tarsus of chinkara comprised of five bones both grossly and radiographically, settled in three transverse rows: tibial and fibular tarsal in the proximal, central and fourth fused tarsal in the middle row, the first, second and third fused tarsal in the distal row. The fibular tarsal was the largest and longest bone of the hock, situated on the lateral side and had a bulbous tuber calcis 'point of the hock' at the proximal extremity which projects upward and backward. The average maximum height and breadth for fibular tarsal was 5.61 ± 0.23 cm and 2.06 ± 0.13 cm, respectively. The tibial tarsal bones were the 2nd largest bone of the proximal row and lie on the medial side of the tarsus bears trochlea at either end. The average maximum height and breadth for tibial tarsal was 2.79 ± 0.05 cm and 1.74 ± 0.01 cm, respectively. The central and the fourth tarsals were fused to form a large bone which extends across the entire width of the tarsus and articulates with all bones of the tarsus. A nutrient foramen was present in the center of the non auricular area, more prominent on the ventral surface. The average maximum height and breadth for central and fourth fused tarsal was 1.51 ± 0.13 cm and 2.08 ± 0.07 cm, respectively. The first tarsal was a quadrilateral piece of bone placed on the poteriomedial surface of the hock. The greatest length and maximum breadth of the first tarsal was 0.94 ± 0.01 cm and 1.01 ± 0.01 cm, respectively. The second and third fused tarsal bone resembles the central but was smaller and triangular in outline. It was situated between the central above and the large metatarsal bone below. The greatest length and maximum breadth of second and third fused tarsal was 0.98 ± 0.01 cm and 1.49 ± 0.01 cm.Keywords: chinkara, morphometry, radiography, tarsal bone
Procedia PDF Downloads 171649 Novel Molecular Mechanisms Involved in Macrophage Phenotypic Polarization
Authors: Mansi Srivastava, Uzma Saqib, Adnan Naim, Anjali Roy, Dongfang Liu, Deepak Bhatnagar, Ravinder Ravinder, Mirza S. Baig
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Macrophages polarize to proinflammatory M1 or anti-inflammatory M2 states with distinct physiological functions. This transition within the M1 to M2 phenotypes decides the nature, duration, and severity of an inflammatory response. However, inspite of a substantial understanding of the fate of these phenotypes, the underlying molecular mechanisms are not well understood. We have investigated the role of Neuronal nitric oxide synthase (NOS1) mediated regulation of Activator protein 1 (AP-1) transcription factor in macrophages as a critical effector of macrophage phenotypic change. Activator protein 1 (AP-1) is a group of dimeric transcription factors composed of jun, Fos, and ATF family proteins. We determined that NOS1-derived nitric oxide (NO) facilitate Fos and jun interaction which induces IL12 & IL23 expression. Pharmacological inhibition of NOS1 inhibits Fos and jun interaction but increases ATF2 and Fos dimerization. Switching of Fos and jun dimer to ATF2 and jun dimerization switches phenotype from IL–12high IL-23high IL-10low to IL–12low IL-23lowIL-10high phenotype, respectively. Together, these findings highlight a key role of the TLR4-NOS1-AP1 signaling axis in regulating macrophage polarization.Keywords: inflammation, macrophage, lipopolysaccharide (LPS), proinflammatory cytokines, activator protein 1 (AP-1), neuronal nitric oxide synthase (NOS1)
Procedia PDF Downloads 284648 Bone Mineral Density and Trabecular Bone Score in Ukrainian Women with Obesity
Authors: Vladyslav Povoroznyuk, Nataliia Dzerovych, Larysa Martynyuk, Tetiana Kovtun
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Obesity and osteoporosis are the two diseases whose increasing prevalence and high impact on the global morbidity and mortality, during the two recent decades, have gained a status of major health threats worldwide. Obesity purports to affect the bone metabolism through complex mechanisms. Debated data on the connection between the bone mineral density and fracture prevalence in the obese patients are widely presented in literature. There is evidence that the correlation of weight and fracture risk is site-specific. The aim of this study was to evaluate the Bone Mineral Density (BMD) and Trabecular Bone Score (TBS) in the obese Ukrainian women. We examined 1025 40-89-year-old women, divided them into the groups according to their body mass index: Group a included 360 women with obesity whose BMI was ≥30 kg/m2, and Group B – 665 women with no obesity and BMI of < 30 kg/m2. The BMD of total body, lumbar spine at the site L1-L4, femur and forearm were measured by DXA (Prodigy, GEHC Lunar, Madison, WI, USA). The TBS of L1-L4 was assessed by means of TBS iNsight® software installed on our DXA machine (product of Med-Imaps, Pessac, France). In general, obese women had a significantly higher BMD of lumbar spine, femoral neck, proximal femur, total body, and ultradistal forearm (p<0.001) in comparison with women without obesity. The TBS of L1-L4 was significantly lower in obese women compared to non-obese women (p<0.001). The BMD of lumbar spine, femoral neck and total body differed to a significant extent in women of 40-49, 50-59, 60-69, and 70-79 years (p<0.05). At same time, in women aged 80-89 years the BMD of lumbar spine (p=0.09), femoral neck (p=0.22) and total body (p=0.06) barely differed. The BMD of ultradistal forearm was significantly higher in women of all age groups (p<0.05). The TBS of L1-L4 in all the age groups tended to reveal the lower parameters in obese women compared with the non-obese; however, those data were not statistically significant. By contrast, a significant positive correlation was observed between the fat mass and the BMD at different sites. The correlation between the fat mass and TBS of L1-L4 was also significant, although negative. Women with vertebral fractures had a significantly lower body weight, body mass index and total body fat mass in comparison with women without vertebral fractures in their anamnesis. In obese women the frequency of vertebral fractures was 27%, while in women without obesity – 57%.Keywords: obesity, trabecular bone score, bone mineral density, women
Procedia PDF Downloads 443647 In vivo Evidence of Protective Effect of Hyparrhenia Hirta against Nitrate-Induced Genotoxicity
Authors: H. Bouaziz-Ketata, G. Ben Salah, Z. Aidi, C. Kallel, H. Kammoun, F. Fakhfakh, N. Zeghal
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The present study was performed to evaluate the potential protective effect of Hyparrhenia hirta methanolic extract in NaNO3-induced genotoxic and hematotoxic effects. Male Wistar rats were randomly divided into three groups: a control group and two treated groups during 50 days with NaNO3 administered at a dose of 400 mg kg-1 bw either alone in drinking water or co-administered with Hyparrhenia hirta at a dose of 200 mg kg-1 bw. NaNO3 treatment showed a significant increase in the frequencies of total chromosomal aberrations, aberrant metaphases and micronucleus in bone-marrow cells. In parallel, the NaNO3-treated group showed a significant decrease in red blood cell count, hemoglobin and hematocrit and a significant increase in total white blood cell, in neutrophil and eosinophil counts. Platelet count, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration remained unchanged in treated groups compared to those of controls. Hyparrhenia hirta methanolic extract appeared to be effective against genotoxic and hematotoxic changes induced by nitrate, as evidenced by the improvement of the markers cited above.Keywords: Hyparrhenia hirta, sodium nitrate, erythrocytes, genotoxicity
Procedia PDF Downloads 258646 Biocompatible Porous Titanium Scaffolds Produced Using a Novel Space Holder Technique
Authors: Yunhui Chen, Damon Kent, Matthew Dargusch
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Synthetic scaffolds are a highly promising new approach to replace both autografts and allografts to repair and remodel damaged bone tissue. Biocompatible porous titanium scaffold was manufactured through a powder metallurgy approach. Magnesium powder was used as space holder material which was compacted with titanium powder and removed during sintering. Evaluation of the porosity and mechanical properties showed a high level of compatibility with human bone. Interconnectivity between pores is higher than 95% for porosity as low as 30%. The elastic moduli are 39 GPa, 16 GPa and 9 GPa for 30%, 40% and 50% porosity samples which match well to that of natural bone (4-30 GPa). The yield strengths for 30% and 40% porosity samples of 315 MPa and 175 MPa are superior to that of human bone (130-180 MPa). In-vitro cell culture tests on the scaffold samples using Human Mesenchymal Stem Cells (hMSCs) demonstrated their biocompatibility and indicated osseointegration potential. The scaffolds allowed cells to adhere and spread both on the surface and inside the pore structures. With increasing levels of porosity/interconnectivity, improved cell proliferation is obtained within the pores. It is concluded that samples with 30% porosity exhibit the best biocompatibility. The results suggest that porous titanium scaffolds generated using this manufacturing route have excellent potential for hard tissue engineering applications.Keywords: scaffolds, MG-63 cell culture, titanium, space holder
Procedia PDF Downloads 235645 The Role of Human Cartilage Glycoprotein in Osteoporosis and Osteoporotic Fractures
Authors: Hasanzade Nazenin, Hasanova Naila
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According to the WHO, osteoporosis is one of the most important health problems in the world and occupies the 4th place in its importance after cardiovascular pathology, oncological diseases and diabetes mellitus. The significance of osteoporosis is determined by its prevalence among the population, the severity of the course, the cause of death, disability, reduced quality of life, high economic costs for prevention and treatment. Osteoporosis is a systemic skeletal disease characterized by a decrease in bone mass and a violation of the structure of bone tissue, leading to an increase in bone fragility and the risk of fractures. Osteoporosis is manifested by low-traumatic fractures. Due to the complexity of the recovery process, the treatment of osteoporotic fractures is one of the important problems of modern traumatology. Diagnostic markers are needed to monitor the recovery period. Human cartilage glycoprotein -39, which has been studied so far in inflammatory processes in the bones, may allow the development of the correct treatment regimen, reflecting the level of metabolic processes in the bone tissue. The study was performed to examine the dynamics of human cartilage glycoprotein-39 (HCgp39) in the blood serum during osteoporosis and fracture healing. The material of the study is formed by the examination results of 68 people aged 38-83. Group I - control group consisted of 14 practically healthy people, group II - 14 patients with osteoporosis, group III - 15 patients with non-osteoporotic fractures, group IV - 25 patients with osteoporotic fractures. In groups, they were analyzed by enzyme-linked immunosorbent assay 3 times during the first month. As a result, in the first month of the recovery period, no significant difference was observed in the HCgp39 dynamics for groups II and IV (p> 0.05). However, there was a significant reduction in group III (p <0.05). As no osteoporotic changes were observed in this patient group, bone healing was rapid and it was possible to monitor the dynamics of HCgp39 changes within 1 month. Patients with osteoporosis and other bone fractures in the process of complete recovery need to study HCgp39 more as a diagnostic indicator.Keywords: osteoporosis, osteoporotic fractures, human cartilage glycoprotein, HCgp39
Procedia PDF Downloads 15644 Can Bone Resorption Reduce with Nanocalcium Particles in Astronauts?
Authors: Ravi Teja Mandapaka, Prasanna Kumar Kukkamalla
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Poor absorption of calcium, elevated levels in serum and loss of bone are major problems of astronauts during space travel. Supplementation of calcium could not reveal this problem. In normal condition only 33% of calcium is absorbed from dietary sources. In this paper effect of space environment on calcium metabolism was discussed. Many surprising study findings were found during literature survey. Clinical trials on ovariectomized mice showed that reduction of calcium particles to nano level make them more absorbable and bioavailable. Control of bone loss in astronauts in critical important In Fortification of milk with nana calcium particles showed reduces urinary pyridinoline, deoxypyridinoline levels. Dietary calcium and supplementation do not show much retention of calcium in zero gravity environment where absorption is limited. So, the fortification of foods with nano calcium particles seemed beneficial for astronauts during and after space travel in their speedy recovery.Keywords: nano calcium, astronauts, fortification, supplementation
Procedia PDF Downloads 494643 Radioprotective Effects of Super-Paramagnetic Iron Oxide Nanoparticles Used as Magnetic Resonance Imaging Contrast Agent for Magnetic Resonance Imaging-Guided Radiotherapy
Authors: Michael R. Shurin, Galina Shurin, Vladimir A. Kirichenko
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Background. Visibility of hepatic malignancies is poor on non-contrast imaging for daily verification of liver malignancies prior to radiation therapy on MRI-guided Linear Accelerators (MR-Linac). Ferumoxytol® (Feraheme, AMAG Pharmaceuticals, Waltham, MA) is a SPION agent that is increasingly utilized off-label as hepatic MRI contrast. This agent has the advantage of providing a functional assessment of the liver based upon its uptake by hepatic Kupffer cells proportionate to vascular perfusion, resulting in strong T1, T2 and T2* relaxation effects and enhanced contrast of malignant tumors, which lack Kupffer cells. The latter characteristic has been recently utilized for MRI-guided radiotherapy planning with precision targeting of liver malignancies. However potential radiotoxicity of SPION has never been addressed for its safe use as an MRI-contrast agent during liver radiotherapy on MRI-Linac. This study defines the radiomodulating properties of SPIONs in vitro on human monocyte and macrophage cell lines exposed to 60Go gamma-rays within clinical radiotherapy dose range. Methods. Human monocyte and macrophages cell line in cultures were loaded with a clinically relevant concentration of Ferumoxytol (30µg/ml) for 2 and 24 h and irradiated to 3Gy, 5Gy and 10Gy. Cells were washed and cultured for additional 24 and 48 h prior to assessing their phenotypic activation by flow cytometry and function, including viability (Annexin V/PI assay), proliferation (MTT assay) and cytokine expression (Luminex assay). Results. Our results reveled that SPION affected both human monocytes and macrophages in vitro. Specifically, iron oxide nanoparticles decreased radiation-induced apoptosis and prevented radiation-induced inhibition of human monocyte proliferative activity. Furthermore, Ferumoxytol protected monocytes from radiation-induced modulation of phenotype. For instance, while irradiation decreased polarization of monocytes to CD11b+CD14+ and CD11bnegCD14neg phenotype, Ferumoxytol prevented these effects. In macrophages, Ferumoxytol counteracted the ability of radiation to up-regulate cell polarization to CD11b+CD14+ phenotype and prevented radiation-induced down-regulation of expression of HLA-DR and CD86 molecules. Finally, Ferumoxytol uptake by human monocytes down-regulated expression of pro-inflammatory chemokines MIP-1α (Macrophage inflammatory protein 1α), MIP-1β (CCL4) and RANTES (CCL5). In macrophages, Ferumoxytol reversed the expression of IL-1RA, IL-8, IP-10 (CXCL10) and TNF-α, and up-regulates expression of MCP-1 (CCL2) and MIP-1α in irradiated macrophages. Conclusion. SPION agent Ferumoxytol increases resistance of human monocytes to radiation-induced cell death in vitro and supports anti-inflammatory phenotype of human macrophages under radiation. The effect is radiation dose-dependent and depends on the duration of Feraheme uptake. This study also finds strong evidence that SPIONs reversed the effect of radiation on the expression of pro-inflammatory cytokines involved in initiation and development of radiation-induced liver damage. Correlative translational work at our institution will directly assess the cyto-protective effects of Ferumoxytol on human Kupfer cells in vitro and ex vivo analysis of explanted liver specimens in a subset of patients receiving Feraheme-enhanced MRI-guided radiotherapy to the primary liver tumors as a bridge to liver transplant.Keywords: superparamagnetic iron oxide nanoparticles, radioprotection, magnetic resonance imaging, liver
Procedia PDF Downloads 72642 Ethanol Extract of Potentilla pradoxa Nutt Inhibits LPS-induced Inflammatory Responses via NF-κB and AP-1 Inactivation
Authors: Hae-Jun Lee, Ji-Sun Shin, Kyung-Tae Lee
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Potentilla species (Rosasease) have been used in traditional medicine to treat different ailment, disease or malady. In this study, we investigated the anti-inflammatory effects of ethanol extracts of NUTT (EPP) in lipopolysaccharide (LPS)-induced Raw 264.7 macrophages and septic mice. EPP suppressed LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production in LPS-induced Raw 264.7 macrophages. Consistent with these observations, EPP reduced the expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) by downregulation of their promoter activities. EPP inhibited tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) at production and mRNA levels. Molecularly, EPP attenuated the LPS-induced transcriptional activity, and DNA-binding activity of nuclear factor-κB (NF-κB), and this was associated with a decrease of translocation and phosphorylation of p65 NF-κB by inhibiting the inhibitory κB-α (IκB-α) degradation and IκB kinase-α/β (IKK-α/β) phosphorylation. Furthermore, EPP suppressed the LPS-induced activation of activator protein-1 (AP-1) by reducing the expression of c-Fos and c-Jun in nuclear. EPP also reduced the phosphorylation of mitogen-activated protein kinase (MAPK), such as p38 MAPK and c-Jun N-terminal kinase/stress-activated protein kinase (JNK). In a sepsis model, pretreatment with EPP reduced the LPS-induced lethality. Collectively, these results suggest that the anti-inflammatory effects of EPP were associated with the suppression of NF-κB and AP-1 activation, and support its possible therapeutic role for the treatment of sepsis.Keywords: anti-inflammation, activator protein-1, nuclear factor κB, Potentilla paradoxa Nutt
Procedia PDF Downloads 334641 Synthesis and Characterization of Hydroxyapatite from Biowaste for Potential Medical Application
Authors: M. D. H. Beg, John O. Akindoyo, Suriati Ghazali, Nitthiyah Jeyaratnam
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Over the period of time, several approaches have been undertaken to mitigate the challenges associated with bone regeneration. This includes but not limited to xenografts, allografts, autografts as well as artificial substitutions like bioceramics, synthetic cements and metals. The former three techniques often come along with peculiar limitation and problems such as morbidity, availability, disease transmission, collateral site damage or absolute rejection by the body as the case may be. Synthetic routes remain the only feasible alternative option for treatment of bone defects. Hydroxyapatite (HA) is very compatible and suitable for this application. However, most of the common methods for HA synthesis are either expensive, complicated or environmentally unfriendly. Interestingly, extraction of HA from bio-wastes have been perceived not only to be cost effective, but also environment friendly. In this research, HA was synthesized from bio-waste: namely bovine bones through three different methods which are hydrothermal chemical processes, ultrasound assisted synthesis and ordinary calcination techniques. Structure and property analysis of the HA was carried out through different characterization techniques such as TGA, FTIR, and XRD. All the methods applied were able to produce HA with similar compositional properties to biomaterials found in human calcified tissues. Calcination process was however observed to be more efficient as it eliminated all the organic components from the produced HA. The HA synthesized is unique for its minimal cost and environmental friendliness. It is also perceived to be suitable for tissue and bone engineering applications.Keywords: hydroxyapatite, bone, calcination, biowaste
Procedia PDF Downloads 249640 Finite Element Analysis of Mini-Plate Stabilization of Mandible Fracture
Authors: Piotr Wadolowski, Grzegorz Krzesinski, Piotr Gutowski
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The aim of the presented investigation is to recognize the possible mechanical issues of mini-plate connection used to treat mandible fractures and to check the impact of different factors for the stresses and displacements within the bone-stabilizer system. The mini-plate osteosynthesis technique is a common type of internal fixation using metal plates connected to the fractured bone parts by a set of screws. The selected two types of plate application methodology used by maxillofacial surgeons were investigated in the work. Those patterns differ in location and number of plates. The bone geometry was modeled on the base of computed tomography scans of hospitalized patient done just after mini-plate application. The solid volume geometry consisting of cortical and cancellous bone was created based on gained cloud of points. Temporomandibular joint and muscle system were simulated to imitate the real masticatory system behavior. Finite elements mesh and analysis were performed by ANSYS software. To simulate realistic connection behavior nonlinear contact conditions were used between the connecting elements and bones. The influence of the initial compression of the connected bone parts or the gap between them was analyzed. Nonlinear material properties of the bone tissues and elastic-plastic model of titanium alloy were used. The three cases of loading assuming the force of magnitude of 100N acting on the left molars, the right molars and the incisors were investigated. Stress distribution within connecting plate shows that the compression of the bone parts in the connection results in high stress concentration in the plate and the screws, however the maximum stress levels do not exceed material (titanium) yield limit. There are no significant differences between negative offset (gap) and no-offset conditions. The location of the external force influences the magnitude of stresses around both the plate and bone parts. Two-plate system gives generally lower von Misses stress under the same loading than the one-plating approach. Von Mises stress distribution within the cortical bone shows reduction of high stress field for the cases without the compression (neutral initial contact). For the initial prestressing there is a visible significant stress increase around the fixing holes at the bottom mini-plate due to the assembly stress. The local stress concentration may be the reason of bone destruction in those regions. The performed calculations prove that the bone-mini-plate system is able to properly stabilize the fractured mandible bone. There is visible strong dependency between the mini-plate location and stress distribution within the stabilizer structure and the surrounding bone tissue. The results (stresses within the bone tissues and within the devices, relative displacements of the bone parts at the interface) corresponding to different models of the connection provide a basis for the mechanical optimization of the mini-plate connections. The results of the performed numerical simulations were compared to clinical observation. They provide information helpful for better understanding of the load transfer in the mandible with the stabilizer and for improving stabilization techniques.Keywords: finite element modeling, mandible fracture, mini-plate connection, osteosynthesis
Procedia PDF Downloads 246639 Association of Clostridium difficile Infection and Bone Cancer
Authors: Daniela Prado, Lexi Frankel, Amalia Ardeljan, Lokesh Manjani, Matthew Cardeiro, Omar Rashid
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Background: Clostridium difficile (C. diff) is a gram-positive bacterium that is known to cause life-threatening diarrhea and severe inflammation of the colon. It originates as an alteration of the gut microbiome and can be transmitted through spores. Recent studies have shown a high association between the development of C. diff in cancer patients due to extensive hospitalization. However, research is lacking regarding C. diff’s association in the causation or prevention of cancer. The objective of this study was to therefore assess the correlation between Clostridium difficile infection (CDI) and the incidence of bone cancer. Methods: This retrospective analysis used data provided by a Health Insurance Portability and Accountability Act (HIPAA) compliant national database to evaluate the patients infected versus patients not infected with C. diff using ICD-10 and ICD-9 codes. Access to the database was granted by the Holy Cross Health, Fort Lauderdale, for the purpose of academic research. Standard statistical methods were used. Results: Between January 2010 and December 2019, the query was analyzed and resulted in 78863 patients in both the infected and control group, respectively. The two groups were matched by age range and CCI score. The incidence of bone cancer was 659 patients (0.835%) in the C. diff group compared to 1941 patients (2.461%) in the control group. The difference was statistically significant by a P-value < 2.2x10^-16 with an odds ratio (OR)= 0.33 (0.31-0.37) with a 95% confidence interval (CI). Treatment for CDI was analyzed for both C. diff infected and noninfected populations. 91 out of 16,676 (0.55%) patients with a prior C. diff infection and treated with antibiotics were compared to the control group were 275 out of 16,676 (1.65%) patients with no history of CDI and received antibiotic treatment. Results remained statistically significant by P-value <2.2x10-16 with an OR= 0.42 (0.37, 0.48). and a 95% CI. Conclusion: The study shows a statistically significant correlation between C. diff and a reduced incidence of bone cancer. Further evaluation is recommended to assess the potential of C. difficile in reducing bone cancer incidence.Keywords: bone cancer, colitis, clostridium difficile, microbiome
Procedia PDF Downloads 277638 Piled Critical Size Bone-Biomimetic and Biominerizable Nanocomposites: Formation of Bioreactor-Induced Stem Cell Gradients under Perfusion and Compression
Authors: W. Baumgartner, M. Welti, N. Hild, S. C. Hess, W. J. Stark, G. Meier Bürgisser, P. Giovanoli, J. Buschmann
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Perfusion bioreactors are used to solve problems in tissue engineering in terms of sufficient nutrient and oxygen supply. Such problems especially occur in critical size grafts because vascularization is often too slow after implantation ending up in necrotic cores. Biominerizable and biocompatible nanocomposite materials are attractive and suitable scaffold materials for bone tissue engineering because they offer mineral components in organic carriers – mimicking natural bone tissue. In addition, human adipose derived stem cells (ASCs) can potentially be used to increase bone healing as they are capable of differentiating towards osteoblasts or endothelial cells among others. In the present study, electrospun nanocomposite disks of poly-lactic-co-glycolic acid and amorphous calcium phosphate nanoparticles (PLGA/a-CaP) were seeded with human ASCs and eight disks were stacked in a bioreactor running with normal culture medium (no differentiation supplements). Under continuous perfusion and uniaxial cyclic compression, load-displacement curves as a function of time were assessed. Stiffness and energy dissipation were recorded. Moreover, stem cell densities in the layers of the piled scaffold were determined as well as their morphologies and differentiation status (endothelial cell differentiation, chondrogenesis and osteogenesis). While the stiffness of the cell free constructs increased over time caused by the transformation of the a-CaP nanoparticles into flake-like apatite, ASC-seeded constructs showed a constant stiffness. Stem cell density gradients were histologically determined with a linear increase in the flow direction from the bottom to the top of the 3.5 mm high pile (r2 > 0.95). Cell morphology was influenced by the flow rate, with stem cells getting more roundish at higher flow rates. Less than 1 % osteogenesis was found upon osteopontin immunostaining at the end of the experiment (9 days), while no endothelial cell differentiation and no chondrogenesis was triggered under these conditions. All ASCs had mainly remained in their original pluripotent status within this time frame. In summary, we have fabricated a critical size bone graft based on a biominerizable bone-biomimetic nanocomposite with preserved stiffness when seeded with human ASCs. The special feature of this bone graft was that ASC densities inside the piled construct varied with a linear gradient, which is a good starting point for tissue engineering interfaces such as bone-cartilage where the bone tissue is cell rich while the cartilage exhibits low cell densities. As such, this tissue-engineered graft may act as a bone-cartilage interface after the corresponding differentiation of the ASCs.Keywords: bioreactor, bone, cartilage, nanocomposite, stem cell gradient
Procedia PDF Downloads 308637 Bone Mineral Density in Long-Living Patients with Coronary Artery Disease
Authors: Svetlana V. Topolyanskaya, Tatyana A. Eliseeva, Olga N. Vakulenko, Leonid I. Dvoretski
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Introduction: Limited data are available on osteoporosis in centenarians. Therefore, we evaluated bone mineral density in long-living patients with coronary artery disease (CAD). Methods: 202 patients hospitalized with CAD were enrolled in this cross-sectional study. The patients' age ranged from 90 to 101 years. The majority of study participants (64.4%) were women. The main exclusion criteria were any disease or medication that can lead to secondary osteoporosis. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. Results: Normal lumbar spine BMD was observed in 40.9%, osteoporosis – in 26.9%, osteopenia – in 32.2% of patients. Normal proximal femur BMD values were observed in 21.3%, osteoporosis – in 39.9%, and osteopenia – in 38.8% of patients. Normal femoral neck BMD was registered only in 10.4% of patients, osteoporosis was observed in 60.4%, osteopenia in 29.2%. Significant positive correlation was found between all BMD values and body mass index of patients (p < 0.001). Positive correlation was registered between BMD values and serum uric acid (p=0.0005). The likelihood of normal BMD values with hyperuricemia increased 3.8 times, compared to patients with normal uric acid, who often have osteoporosis (Odds Ratio=3.84; p = 0.009). Positive correlation was registered between all BMD values and body mass index (p < 0.001). Positive correlation between triglycerides levels and T-score (p=0.02), but negative correlation between BMD and HDL-cholesterol (p=0.02) were revealed. Negative correlation between frailty severity and BMD values (p=0.01) was found. Positive correlation between BMD values and functional abilities of patients assessed using Barthel index (r=0,44; p=0,000002) and IADL scale (r=0,36; p=0,00008) was registered. Fractures in history were observed in 27.6% of patients. Conclusions: The study results indicate some features of BMD in long-livers. In the study group, significant relationships were found between bone mineral density on the one hand, and patients' functional abilities on the other. It is advisable to further study the state of bone tissue in long-livers involving a large sample of patients.Keywords: osteoporosis, bone mineral density, centenarians, coronary artery disease
Procedia PDF Downloads 144636 Tuberculous Osteomyelitis Mimicking Tumours and Tumour-Like Lesions of Bone: Clinico-Radiologic Study of 22 Patients
Authors: Parveen Kundu, Zile Singh, Kunika Kundu, Swaran Kaur
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Context: Tuberculous osteomyelitis is a relatively uncommon condition that can present with various clinical and radiological features, often mimicking bone tumors or tumor-like lesions. In endemic countries like India, tuberculosis should be considered as a potential differential diagnosis for lytic bone lesions. This study aimed to highlight the different presentations of tuberculosis that can mimic tumors or tumor-like lesions in bone and emphasize the successful outcome of antitubercular therapy (ATT) in treating these cases. Research Aim: The main objective of this research was to explore the varied presentations of tuberculosis that mimic bone tumors or tumor-like lesions both clinically and radiologically, focusing on different bones. The study aimed to raise awareness among clinicians about this possibility and highlight the importance of histopathological confirmation before initiating treatment for lytic bone lesions. Methodology: This study utilized a retrospective review of 22 patients with suspected lytic bone lesions, who were subsequently diagnosed with tuberculous osteomyelitis through histopathological examination. The cases were collected over a period of ten years. Eleven cases required curettage for extensive lesions with sequestrations, while all 22 patients received 12 months of antitubercular therapy. Findings: The study included 14 male and 8 female patients, ranging in age from 3 to 61 years, with an average age of 22.05. The clinical and radiological presentations varied, with examples including bone cysts in the metaphyseal area of long bones, lesions resembling chondroblastomas, giant cell tumors, and osteoid osteoma, as well as multifocal lytic lesions resembling metastasis or multiple myeloma. One patient had lesions in both the clavicle and hand. Lesions mimicking chondromas were also observed in the phalanges of the hand and foot metatarsal. All patients showed resolution of the lesions and no residual disability following ATT. Theoretical Importance: This study highlights the importance of considering tuberculosis as a potential differential diagnosis for lytic bone lesions, particularly in endemic regions. It emphasizes the need for histopathological confirmation to accurately diagnose tuberculous osteomyelitis, as this is considered the gold standard. Data Collection and Analysis Procedures: Data for this study were collected retrospectively from medical records and radiological images of the 22 patients. The cases were analyzed based on clinical presentation, radiological findings, and histopathological confirmation. The outcomes of antitubercular therapy were also assessed. The data were summarized and presented descriptively. Question Addressed: This study aimed to address the question of how tuberculosis can mimic different bone tumors and tumor-like lesions clinically and radiologically. It also aimed to assess the successful outcome of antitubercular therapy in treating these cases. Conclusion: Tuberculous osteomyelitis can present with varied clinical and radiological features, often mimicking bone tumors or tumor-like lesions. Clinicians should consider tuberculosis as a potential diagnosis for lytic bone lesions, especially in endemic areas. Histopathological confirmation is essential for accurate diagnosis. Antitubercular therapy is an effective treatment for tuberculous osteomyelitis, leading to the resolution of the lesions with no residual disability.Keywords: tuberculosis, tumor, curettage, bone
Procedia PDF Downloads 90635 Synthesis of Tricalcium Phosphate Substituted with Magnesium Ions for Bone Regeneration
Authors: Andreia Cucuruz, Cristina Daniela Ghitulica, Georgeta Voicu, Cristina Busuioc
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Ceramics based on calcium phosphates have lately increased attention for tissue engineering because they can be used as substitute bones or for bone regeneration since they mimic very well the nanostructure of tough bone tissue, but also because of other advantages such as a very good biocompatibility and osseointegration. This study aims the preparation and characterization of ceramic materials on the basis of TCP (Ca₃(PO₄)₂), within which calcium ions are substituted by magnesium ions (Mg²⁺) in order to improve the regenerative properties of these materials. TCP-Mg material was synthesized by chemical precipitation method using calcium oxide (CaO) and phosphoric acid (H₃PO₄) as precursors. The objective was to obtain powders with different concentrations of Mg in order to analyze the effect of magnesium ions on the physicochemical properties of phosphate ceramics and in vitro degradation in simulated biological fluid (SBF). Ceramic powders were characterized in vitro but also from the compositional and microstructural point of view. TCP_Mg powders were prepared through wet chemical method from calcium oxide (CaO), magnesium oxide nanopowder (MgO < 50 nm particle size (BET) Sigma Aldrich), phosphoric acid (H₃PO₄ - 85 wt.% in H₂O, 99.99% trace metals basis - Sigma Aldrich). In order to determine the quantities of raw materials, calculations were performed to obtain HAp with Ca/P ratio of 1.5.Keywords: bone regeneration, magnesium substitution, tricalcium phosphate, tissue engineering
Procedia PDF Downloads 346634 Restoring Total Form and Function in Patients with Lower Limb Bony Defects Utilizing Patient-Specific Fused Deposition Modelling- A Neoteric Multidisciplinary Reconstructive Approach
Authors: Divya SY. Ang, Mark B. Tan, Nicholas EM. Yeo, Siti RB. Sudirman, Khong Yik Chew
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Introduction: The importance of the amalgamation of technological and engineering advances with surgical principles of reconstruction cannot be overemphasized. With earlier detection of cancer, consequences of high-speed living and neglect, like traumatic injuries and infection, resulting in increasingly younger patients with bone defects. This may result in malformations and suboptimal function that is more noticeable and palpable in the younger, active demographic. Our team proposes a technique that encapsulates a mesh of multidisciplinary effort, tissue engineering and reconstructive principles. Methods/Materials: Our patient was a young competitive footballer in his early 30s who was diagnosed with submandibular adenoid cystic carcinoma with bony involvement. He was thus counselled for a right hemi mandibulectomy, the floor of mouth resection, right selective neck dissection, tracheostomy, and free fibular flap reconstruction of his mandible and required post-operative radiotherapy. Being young and in his prime sportsman years, he was unable to accept the morbidities associated with using his fibula to reconstruct his mandible despite it being the gold standard reconstructive option. The fibula is an ideal vascularized bone flap because it’s reliable and easily shaped with relatively minimal impact on functional outcomes. The fibula contributes to 30% of weightbearing and is the attachment for the lateral compartment muscles; it is stronger in footballers concerning lateral bending. When harvesting the fibula, the distal 6-8cm and up to 10% of the total length is preserved to maintain the ankle’s stability, thus, minimizing the impact on daily activities. There are studies that have noted gait variability post-operatively. Therefore, returning to a premorbid competitive level may be doubtful. To improve his functional outcomes, the decision was made to try and restore the fibula's form and function. Using the concept of Fused Deposition Modelling (FDM), our team comprising of Plastics, Otolaryngology, Orthopedics and Radiology, worked with Osteopore to design a 3D bioresorbable implant to regenerate the fibula defect (14.5cm). Bone marrow was harvested via reaming the contralateral hip prior to the wide resection. 30mls of his blood was obtained for extracting platelet rich plasma. These were packed into the Osteopore 3D-printed bone scaffold. This was then secured into the fibula defect with titanium plates and screws. The flexor hallucis longus and soleus were anchored along the construct and intraosseous membrane, done in a single setting. Results: He was reviewed closely as an outpatient over 10 months post operatively. He reported no discernable loss or difference in ankle function. He is satisfied and back in training and our team has video and photographs that substantiate his progress. Conclusion: FDM allows regeneration of long bone defects. However, we aimed to also restore his eversion and inversion that is imperative for footballers and hence reattached his previously dissected muscles along the length of the Osteopore implant. We believe that the reattachment of the muscle stabilizes not only the construct but allows optimum muscle tensioning when moving his ankle. This is a simple but effective technique in restoring complete function and form in a young patient whose minute muscle control is imperative to life.Keywords: fused deposition modelling, functional reconstruction, lower limb bony defects, regenerative surgery, 3D printing, tissue engineering
Procedia PDF Downloads 73633 Suppression of Immunostimulatory Function of Dendritic Cells and Prolongation of Skin Allograft Survival by Dryocrassin
Authors: Hsin-Lien Lin, Ju-Hui Fu
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Dendritic cells (DCs) are the major professional antigen-presenting cells for the development of optimal T-cell immunity. DCs can be used as pharmacological targets to screen novel biological modifiers for the treatment of harmful immune responses, such as transplantation rejection. Dryopteris crassirhizoma Nakai (Aspiadaceae) is used for traditional herbal medicine in the region of East Asia. The root of this fern plant has been listed for treating inflammatory diseases. Dryocrassin is the tetrameric phlorophenone component derived from Dryopteris. Here, we tested the immunomodulatory potential of dryocrassin on lipopolysaccharide (LPS)-stimulated activation of mouse bone marrow-derived DCs in vitro and in skin allograft transplantation in vivo. Results demonstrated that dryocrassin reduced the secretion of tumor necrosis factor-α, interleukin-6, and interleukin-12p70 by LPS-stimulated DCs. The expression of LPS-induced major histocompatibility complex class II, CD40, and CD86 on DCs was also blocked by dryocrassin. Moreover, LPS-stimulated DC-elicited allogeneic T-cell proliferation was lessened by dryocrassin. In addition, dryocrassin inhibited LPS-induced activation of IϰB kinase, JNK/p38 mitogen-activated protein kinase, as well as the translocation of NF-ϰB. Treatment with dryocrassin obviously diminished 2,4-dinitro-1-fluorobenzene- induced delayed-type hypersensitivity and prolonged skin allograft survival. Dryocrassin may be one of the potent immunosuppressive agents for transplant rejection through the destruction of DC maturation and function.Keywords: dryocrassin, dendritic cells, immunosuppression, skin allograft
Procedia PDF Downloads 386632 Development of Cationic Gelatin Nanoparticles as an Antigen-Carrier for Mucosal Immunization
Authors: Ping-Lun Jiang, Hung-Jun Lin, Shen-Fu Lin, Mei-Yin Chien, Ting-Wei Li, Chun-Han Lin, Der-Zen Liu
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Mucosal vaccine induces both mucosal (secretory IgA) and systemic immune responses and it is considered an ideal vaccination strategy for prevention of infectious diseases. One important point to be considered in mucosal vaccination is effective antigen delivery system which can manage effective delivery of antigen to antigen-presenting cells (APCs) of mucosal. In the present study, cationic gelatin nanoparticles were prepared as ideal carriers for more efficient antigen delivery. The average diameter of cationic gelatin nanoparticle was approximate 190 nm, and the zeta potential was about +45 mV, then ovalbumin (OVA) was physically absorbed onto cationic gelatin nanoparticle. The OVA absorption rate was near 95% the zeta potential was about +20 mV. We show that cationic gelatin nanoparticle effectively facilitated antigen uptake by mice bone marrow-derived dendritic cells (mBMDCs) and RAW264.7 cells and induced higher levels of pro-inflammatory cytokines. C57BL/6 mice twice immunized intranasally with OVA-absorbed cationic gelatin nanoparticle induced high levels of OVA-specific IgG in the serum and IgA in their in the nasal and lung wash fluid. These results indicate that nasal administration of cationic gelatin nanoparticles induced both mucosal and systemic immune responses and cationic gelatin nanoparticles might be a potential antigen delivery carrier for further clinical applications.Keywords: antigen delivery, antigen-presenting cells, gelatin nanoparticle, mucosal vaccine
Procedia PDF Downloads 359631 Bacillus cereus Bacteremia and Multi-Organ Failure With Diffuse Brain Hypoxia During Acute Lymphoblastic Leukemia Induction Therapy. A Case Report
Authors: Roni Rachel Mendelson, Caileigh Pudela
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Bacillus cereus is a toxin-producing, facultatively anaerobic gram-positive bacterium that is widely distributed environmentally. It can quickly multiply at room temperature with an abundantly present preformed toxin. When ingested, this toxin can cause gastrointestinal illness, which is the commonly known manifestation of the disease. Bacillus cereus sepsis is a disease that is mostly concerning in the population of the immunocompromised patients. One of them is acute lymphoblastic leukemia’s patients during induction. Pediatric acute lymphoblastic leukemia is a common pediatric hematologic malignancy. It is characterized by the rapid proliferation of poorly differentiated lymphoid progenitor cells inside the bone marrow. We present here a 21-month-old boy undergoing induction chemotherapy for acute lymphoblastic leukemia who developed bacillus sepsis bacteremia and, as a result, multi organ failure leading to seizures and multiple strokes. Our case report highlights the extensive overall and neurological damage that can be caused because of bacillus cereus bacteremia, which can lead to higher mortality rate and decreased in survivorship in a highly curable disease. It is very subtle and difficult to recognize and appears to be deteriorating extremely fast. There should be a low threshold for work up and empiric coverage for neutropenic patients during acute lymphoblastic leukemia induction therapy.Keywords: acute lymphoblastic leukemia, bacillus cereus, immunocompromised, sepsis
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