Search results for: bone morphogenetic signaling
Commenced in January 2007
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Edition: International
Paper Count: 1118

Search results for: bone morphogenetic signaling

908 Static and Dynamic Load on Hip Contact of Hip Prosthesis and Thai Femoral Bones

Authors: K. Chalernpon, P. Aroonjarattham, K. Aroonjarattham

Abstract:

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

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907 Experimental Research of Canine Mandibular Defect Construction with the Controlled Meshy Titanium Alloy Scaffold Fabricated by Electron Beam Melting Combined with BMSCs-Encapsulating Chitosan Hydrogel

Authors: Wang Hong, Liu Chang Kui, Zhao Bing Jing, Hu Min

Abstract:

Objection We observed the repairment effection of canine mandibular defect with meshy Ti6Al4V scaffold fabricated by electron beam melting (EBM) combined with bone marrow mesenchymal stem cells (BMMSCs) encapsulated in chitosan hydrogel. Method Meshy titanium scaffolds were prepared by EBM of commercial Ti6Al4V power. The length of scaffolds was 24 mm, the width was 5 mm and height was 8mm. The pore size and porosity were evaluated by scanning electron microscopy (SEM). Chitosan /Bio-Oss hydrogel was prepared by chitosan, β- sodium glycerophosphate and Bio-Oss power. BMMSCs were harvested from canine iliac crests. BMMSCs were seeded in titanium scaffolds and encapsulated in Chitosan /Bio-Oss hydrogel. The validity of BMMSCs was evaluated by cell count kit-8 (CCK-8). The osteogenic differentiation ability was evaluated by alkaline phosphatase (ALP) activity and gene expression of OC, OPN and CoⅠ. Combination were performed by injecting BMMSCs/ Chitosan /Bio-Oss hydrogel into the meshy Ti6Al4V scaffolds and solidified. 24 mm long box-shaped bone defects were made at the mid-portion of mandible of adult beagles. The defects were randomly filled with BMMSCs/ Chitosan/Bio-Oss + titanium, Chitosan /Bio-Oss+titanium, titanium alone. Autogenous iliac crests graft as control group in 3 beagles. Radionuclide bone imaging was used to monitor the new bone tissue at 2, 4, 8 and 12 weeks after surgery. CT examination was made on the surgery day and 4 weeks, 12 weeks and 24 weeks after surgery. The animals were sacrificed in 4, 12 and 24 weeks after surgery. The bone formation were evaluated by histology and micro-CT. Results: The pores of the scaffolds was interconnected, the pore size was about 1 mm, the average porosity was about 76%. The pore size of the hydrogel was 50-200μm and the average porosity was approximately 90%. The hydrogel were solidified under the condition of 37℃in 10 minutes. The validity and the osteogenic differentiation ability of BMSCs were not affected by titanium scaffolds and hydrogel. Radionuclide bone imaging shown an increasing tendency of the revascularization and bone regeneration was observed in all the groups at 2, 4, 8 weeks after operation, and there were no changes at 12weeks.The tendency was more obvious in the BMMSCs/ Chitosan/Bio-Oss +titanium group and autogenous group. CT, Micro-CT and histology shown that new bone formed increasingly with the time extend. There were more new bone regenerated in BMMSCs/ Chitosan /Bio-Oss + titanium group and autogenous group than the other two groups. At 24 weeks, the autogenous group was achieved bone union. The BMSCs/ Chitosan /Bio-Oss group was seen extensive new bone formed around the scaffolds and more new bone inside of the central pores of scaffolds than Chitosan /Bio-Oss + titanium group and titanium group. The difference was significantly. Conclusion: The titanium scaffolds fabricated by EBM had controlled porous structure, good bone conduction and biocompatibility. Chitosan /Bio-Oss hydrogel had injectable plasticity, thermosensitive property and good biocompatibility. The meshy Ti6Al4V scaffold produced by EBM combined BMSCs encapsulated in chitosan hydrogel had good capacity on mandibular bone defect repair.

Keywords: mandibular reconstruction, tissue engineering, electron beam melting, titanium alloy

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906 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

Abstract:

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

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905 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

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904 Signaling Using Phase Shifting in Wi-Fi Backscatter System

Authors: Chang-Bin Ha, Young-Min Ko, Seongjoo Lee, Hyoung-Kyu Song

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In this paper, the signaling scheme using phase shifting is proposed for the improved performance of the Wi-Fi backscatter system. Because the communication in the Wi-Fi backscatter system is based on on-off modulation and impedance modulation by unit of packet, the data rate is very low compared to the conventional wireless systems. Also, because the Wi-Fi backscatter system is based on the RF-powered device, the achievement of high reliability is difficult. In order to increase the low data rate, the proposed scheme transmits information of multiple bits during one packet period. Also, in order to increase the reliability, the proposed scheme shifts the phase of signal in according to the transmitting information. The simulation result shows that the proposed scheme has the improved throughput performance.

Keywords: phase shifting, RF-powered device, Wi-Fi backscatter system, IoT

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903 Adaptor Protein APPL2 Could Be a Therapeutic Target for Improving Hippocampal Neurogenesis and Attenuating Depressant Behaviors and Olfactory Dysfunctions in Chronic Corticosterone-induced Depression

Authors: Jiangang Shen

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Olfactory dysfunction is a common symptom companied by anxiety- and depressive-like behaviors in depressive patients. Chronic stress triggers hormone responses and inhibits the proliferation and differentiation of neural stem cells (NSCs) in the hippocampus and subventricular zone (SVZ)-olfactory bulb (OB), contributing to depressive behaviors and olfactory dysfunction. However, the cellular signaling molecules to regulate chronic stress mediated olfactory dysfunction are largely unclear. Adaptor proteins containing the pleckstrin homology domain, phosphotyrosine binding domain, and leucine zipper motif (APPLs) are multifunctional adaptor proteins. Herein, we tested the hypothesis that APPL2 could inhibit hippocampal neurogenesis by affecting glucocorticoid receptor (GR) signaling, subsequently contributing to depressive and anxiety behaviors as well as olfactory dysfunctions. The major discoveries are included: (1) APPL2 Tg mice had enhanced GR phosphorylation under basic conditions but had no different plasma corticosterone (CORT) level and GR phosphorylation under stress stimulation. (2) APPL2 Tg mice had impaired hippocampal neurogenesis and revealed depressive and anxiety behaviors. (3) GR antagonist RU486 reversed the impaired hippocampal neurogenesis in the APPL2 Tg mice. (4) APPL2 Tg mice displayed higher GR activity and less capacity for neurogenesis at the olfactory system with lesser olfactory sensitivity than WT mice. (5) APPL2 negatively regulates olfactory functions by switching fate commitments of NSCs in adult olfactory bulbs via interaction with Notch1 signaling. Furthermore, baicalin, a natural medicinal compound, was found to be a promising agent targeting APPL2/GR signaling and promoting adult neurogenesis in APPL2 Tg mice and chronic corticosterone-induced depression mouse models. Behavioral tests revealed that baicalin had antidepressant and olfactory-improving effects. Taken together, APPL2 is a critical therapeutic target for antidepressant treatment.

Keywords: APPL2, hippocampal neurogenesis, depressive behaviors and olfactory dysfunction, stress

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902 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

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901 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

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900 Forced Swim Stress Does Not Induce Structural Chromosomal Aberrations in Rat Bone Marrow

Authors: Mohammad Y. Alfaifi

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Anything that poses a challenge or a threat to our well-being is a stress. Understanding the genetic material and cellular response of rats threatened with Repeated swimming stress provides insights that can influence human health. The aim of the present study was to assess the genetical damage and cytological changes caused by exposure of the test organism (Rattus rattus) to forced swimming stress. For this purpose, animals have been submerged in water path 15 minutes daily for 2 weeks. Following that, we performed a micronuclei (MN) test using MNNCE (Micronucleated normocromatic erythrocytes) and MNPCE (Micronucleated polychromatic erythrocytes), NDI (Nuclear division index) and cytological parameters using NDCI (nuclear division cytotoxicity index), necrotic and apoptotic cells in rat's bone marrow samples. Results showed that there was a slightly but not significant increase in the frequency of micronucleated as well as in cytological parameters in bone marrow cells.

Keywords: submergence stress, micronucleus, NDI, NDCI, toxicity, chromosomal aberrations

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899 Immunomodulatory Effect of Deer Antler Extract

Authors: Kang-Hyun Leem, Myung-Gyou Kim, Hye Kyung Kim

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Velvet antler (VA), the immature antlers of male deer, is traditionally used for thousands of years in Asian countries, such as Korea, China, Taiwan, and Mongolia. It has been considered to improve immune system and physical strength. The goal of this study was to investigate the immunomodulatory effect of deer antler velvet using in vitro system. In the first step, the effects of VA (70% ethanol extract) on the proliferation of splenocytes, bone marrow cell, and macrophages were determined. Next, the effect of VA on the production of nitric oxide and phagocytic activity in macrophage were measured. The results showed that VA treatment increased concanavalin-A stimulated splenocyte, bone marrow cells, and macrophage proliferation in a dose dependent manner. VA at 50 and 100 ug/mL concentrations significantly enhanced the concanavalin-A stimulated splenocyte proliferation by 8.8% and 18.5%, respectively. The proliferation of bone marrow cells, isolated from 5wk-old ICR mice, were increased by 25.2% and 46.5% by 50 and 100 ug/mL VA treatment. RAW 264.7 cell proliferation reached peak value at 50 ug/mL of VA treatment exhibiting 108% of the basal value. Nitric oxide production by RAW 264.7 macrophage cells was slightly reduced by VA treatment but was not statistically significant. Moreover, the phagocytic activity of macrophages was enhanced by VA treatment. These results indicate that VA is effective in immune system.

Keywords: deer antler, splenocyte, bone marrow cells, macrophage proliferation, phagocytosis

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898 Identification of Potential Small Molecule Regulators of PERK Kinase

Authors: Ireneusz Majsterek, Dariusz Pytel, J. Alan Diehl

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PKR-like ER kinase (PERK) is serine/threonie endoplasmic reticulum (ER) transmembrane kinase activated during ER-stress. PERK can activate signaling pathways known as unfolded protein response (UPR). Attenuation of translation is mediated by PERK via phosphorylation of eukaryotic initiation factor 2α (eIF2α), which is necessary for translation initiation. PERK activation also directly contributes to activation of Nrf2 which regulates expression of anti-oxidant enzymes. An increased phosphorylation of eIF2α has been reported in Alzheimer disease (AD) patient hippocampus, indicating that PERK is activated in this disease. Recent data have revealed activation of PERK signaling in non-Hodgkins lymphomas. Results also revealed that loss of PERK limits mammary tumor cell growth in vitro and in vivo. Consistent with these observations, activation of UPR in vitro increases levels of the amyloid precursor protein (APP), the peptide from which beta-amyloid plaques (AB) fragments are derived. Finally, proteolytic processing of APP, including the cleavages that produce AB, largely occurs in the ER, and localization coincident with PERK activity. Thus, we expect that PERK-dependent signaling is critical for progression of many types of diseases (human cancer, neurodegenerative disease and other). Therefore, modulation of PERK activity may be a useful therapeutic target in the treatment of different diseases that fail to respond to traditional chemotherapeutic strategies, including Alzheimer’s disease. Our goal will be to developed therapeutic modalities targeting PERK activity.

Keywords: PERK kinase, small molecule inhibitor, neurodegenerative disease, Alzheimer’s disease

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897 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

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896 Evaluation of Some Serum Proteins as Markers for Myeloma Bone Disease

Authors: V. T. Gerov, D. I. Gerova, I. D. Micheva, N. F. Nazifova-Tasinova, M. N. Nikolova, M. G. Pasheva, B. T. Galunska

Abstract:

Multiple myeloma (MM) is the most frequent plasma cell (PC) dyscrasia that involves the skeleton. Myeloma bone disease (MBD) is characterized by osteolytic bone lesions as a result of increased osteoclasts activity not followed by reactive bone formation due to osteoblasts suppression. Skeletal complications cause significant adverse effects on quality of life and lead to increased morbidity and mortality. Last decade studies revealed the implication of different proteins in osteoclast activation and osteoblast inhibition. The aim of the present study was to determine serum levels of periostin, sRANKL and osteopontin and to evaluate their role as bone markers in MBD. Materials and methods. Thirty-two newly diagnosed MM patients (mean age: 62.2 ± 10.7 years) and 33 healthy controls (mean age: 58.9 ± 7.5 years) were enrolled in the study. According to IMWG criteria 28 patients were with symptomatic MM and 4 with monoclonal gammopathy of undetermined significance (MGUS). In respect to their bone involvement all symptomatic patients were divided into two groups (G): 9 patients with 0-3 osteolytic lesions (G1) and 19 patients with >3 osteolytic lesions and/or pathologic fractures (G2). Blood samples were drawn for routine laboratory analysis and for measurement of periostin, sRANKL and osteopontin serum levels by ELISA kits (Shanghai Sunred Biological Technology, China). Descriptive analysis, Mann-Whitney test for assessment the differences between groups and non-parametric correlation analysis were performed using GraphPad Prism v8.01. Results. The median serum levels of periostin, sRANKL and osteopontin of ММ patients were significantly higher compared to controls (554.7pg/ml (IQR=424.0-720.6) vs 396.9pg/ml (IQR=308.6-471.9), p=0.0001; 8.9pg/ml (IQR=7.1-10.5) vs 5.6pg/ml (IQR=5.1-6.4, p<0.0001 and 514.0ng/ml (IQR=469.3-754.0) vs 387.0ng/ml (IQR=335.9-441.9), p<0.0001, respectively). for assessment of differences between groups and non-parametric correlation analysis were performed using GraphPad Prism v8.01. Statistical significance was found for all tested bone markers between symptomatic MM patients and controls: G1 vs controls (p<0.03), G2 vs controls (p<0.0001) for periostin; G1 vs controls (p<0.0001), G2 vs controls (p<0.0001) for sRANKL; G1 vs controls (p=0.002), G2 vs controls (p<0.0001) for osteopontin, as well between symptomatic MM patients and MGUS patients: G1 vs MGUS (p<0.003), G2 vs MGUS (p=0.003) for periostin; G1 vs MGUS (p<0.05), G2 vs MGUS (p<0.001) for sRANKL; G1 vs MGUS (p=0.011), G2 vs MGUS (p=0.0001) for osteopontin. No differences were detected between MGUS and controls and between patients in G1 and G2 groups. Spearman correlation analysis revealed moderate positive correlation between periostin and beta-2-microglobulin (r=0.416, p=0.018), percentage bone marrow myeloma PC (r=0.432, p=0.014), and serum total protein (r=0.427, p=0.015). Osteopontin levels were also positively related to beta-2-microglobulin (r=0.540, p=0.0014), percentage bone marrow myeloma PC (r=0.423, p=0.016), and serum total protein (r=0.413, p=0.019). Serum sRANKL was only related to beta-2-microglobulin levels (r=0.398, p=0.024). Conclusion: In the present study, serum levels of periostin, sRANKL and osteopontin in newly diagnosed MM patients were evaluated. They gradually increased from MGUS to more advanced stages of MM reflecting the severity of bone destruction. These results support the idea that some new protein markers could be used in monitoring the MBD as a most severe complication of MM.

Keywords: myeloma bone disease, periostin, sRANKL, osteopontin

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895 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

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894 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

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893 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

Abstract:

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

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892 Bone Mineral Density in Long-Living Patients with Coronary Artery Disease

Authors: Svetlana V. Topolyanskaya, Tatyana A. Eliseeva, Olga N. Vakulenko, Leonid I. Dvoretski

Abstract:

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

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891 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

Abstract:

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

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890 Synthesis of Tricalcium Phosphate Substituted with Magnesium Ions for Bone Regeneration

Authors: Andreia Cucuruz, Cristina Daniela Ghitulica, Georgeta Voicu, Cristina Busuioc

Abstract:

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

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889 A Novel Application of CORDYCEPIN (Cordycepssinensis Extract): Maintaining Stem Cell Pluripotency and Improving iPS Generation Efficiency

Authors: Shih-Ping Liu, Cheng-Hsuan Chang, Yu-Chuen Huang, Shih-Yin Chen, Woei-Cherng Shyu

Abstract:

Embryonic stem cells (ES) and induced pluripotnet stem cells (iPS) are both pluripotent stem cells. For mouse stem cells culture technology, leukemia inhibitory factor (LIF) was used to maintain the pluripotency of stem cells in vitro. However, LIF is an expensive reagent. The goal of this study was to find out a pure compound extracted from Chinese herbal medicine that could maintain stem cells pluripotency to replace LIF and improve the iPS generation efficiency. From 20 candidates traditional Chinese medicine we found that Cordycepsmilitaris triggered the up-regulation of stem cells activating genes (Oct4 and Sox2) expression levels in MEF cells. Cordycepin, a major active component of Cordycepsmilitaris, also could up-regulate Oct4 and Sox2 gene expression. Furthermore, we used ES and iPS cells and treated them with different concentrations of Cordycepin (replaced LIF in the culture medium) to test whether it was useful to maintain the pluripotency. The results showed higher expression levels of several stem cells markers in 10 μM Cordycepin-treated ES and iPS cells compared to controls that did not contain LIF, including alkaline phosphatase, SSEA1, and Nanog. Embryonic body formation and differentiation confirmed that 10 μM Cordycepin-containing medium was capable to maintain stem cells pluripotency after four times passages. For mechanism analysis, microarray analysis indicated extracellular matrix and Jak/Stat signaling pathway as the top two deregulated pathways. In ECM pathway, we determined that the integrin αVβ5 expression levels and phosphorylated Src levels increased after Cordycepin treatment. In addition, the phosphorylated Jak2 and phosphorylated Sat3 protein levels were increased after Cordycepin treatment and suppressed with the Jak2 inhibitor, AG490. The expression of cytokines associated with Jak2/Stat3 signaling pathway were also up-regulated by Q-PCR and ELISA assay. Lastly, we used Oct4-GFP MEF cells to test iPS generation efficiency following Cordycepin treatment. We observed that 10 Μm Cordycepin significantly increased the iPS generation efficiency in day 21. In conclusion, we demonstrated Cordycepin could maintain the pluripotency of stem cells through both of ECM and Jak2/Stat3 signaling pathway and improved iPS generation efficiency.

Keywords: cordycepin, iPS cells, Jak2/Stat3 signaling pathway, molecular biology

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888 The Role of Bone Marrow Stem Cells Transplantation in the Repair of Damaged Inner Ear in Albino Rats

Authors: Ahmed Gaber Abdel Raheem, Nashwa Ahmed Mohamed

Abstract:

Introduction: Sensorineural hearing loss (SNHL) is largely caused by the degeneration of the cochlea. Therapeutic options for SNHL are limited to hearing aids and cochlear implants. The cell transplantation approach to the regeneration of hair cells has gained considerable attention because stem cells are believed to accumulate in the damaged sites and have the potential for the repair of damaged tissues. The aim of the work: was to assess the use of bone marrow transplantation in repair of damaged inner ear hair cells in rats after the damage had been inflicted by Amikacin injection. Material and Methods: Thirty albino rats were used in this study. They were divided into three groups. Each group ten rats. Group I: used as control. Group II: Were given Amikacin- intratympanic injection till complete loss of hearing function. This could be assessed by Distortion product Otoacoustic Emission (DPOAEs) and / or auditory brain stem evoked potential (ABR). GroupIII: were given intra-peritoneal injection of bone marrow stem cell after complete loss of hearing caused by Amikacin. Clinical assessment was done using DPOAEs and / or auditory brain stem evoked potential (ABR), before and after bone marrow injection. Histological assessment of the inner ear was done by light and electron microscope. Also, Detection of stem cells in the inner ear by immunohistochemistry. Results: Histological examination of the specimens showed promising improvement in the structure of cochlea that may be responsible for the improvement of hearing function in rats detected by DPOAEs and / or ABR. Conclusion: Bone marrow stem cells transplantation might be useful for the treatment of SNHL.

Keywords: amikacin, hair cells, sensorineural hearing loss, stem cells

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887 Antiproliferative and Apoptotic Effects of an Enantiomerically Pure β-Dipeptide Derivative through PI3K/Akt-Dependent and -Independent Pathways in Human Hormone-Refractory Prostate Cancer Cells

Authors: Mei-Ling Chan, Jin-Ming Wu, Konstantin V. Kudryavtsev, Jih-Hwa Guh

Abstract:

Prostate cancer is one of the most common malignant disease in men. KUD983 is an enantiomerically pure β-dipeptide derivative, which may have anti-cancer effects. In the present study, KUD983 exhibits powerful activity against hormone-refractory prostate cancer (HRPC) PC-3 and DU145 cells. The IC50 values of KUD983 in PC-3 and DU145 cells are 0.56±0.07M and 0.50±0.04 M respectively. KUD983 induced G1 arrest of the cell cycle and subsequent apoptosis associated with the down-regulation of several related proteins including cyclin D1, cyclin E and Cdk4, and the de-phosphorylation of RB. The protein expressions of nuclear and total c-Myc protein, which was able to regulate the expression of both cyclin D1 and cyclin E, were significantly suppressed by KUD983. Phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) is an important signaling pathway that influences the energy metabolism, cell cycle, proliferation, survival and apoptosis of cells, and is associated with numerous other signaling pathways. The Western Blot data revealed that KUD983 inhibited PI3K/Akt and mTOR/p70S6K/4E-BP1 pathways. The transient transfection of constitutively active myristylated Akt (myr-Akt) cDNA significantly reversed KUD983-induced caspase activation but did not abolish the suppression of mTOR/p70S6K/4E-BP1 signaling cascade indicating the presence of both Akt-dependent and -independent pathways. Moreover, KUD983-induced effect was collaborated with the down-regulation of anti-apoptotic Bcl-2 members (e.g., Bcl-2, and Mcl-1) and IAP family members (e.g., survivin). Furthermore, KUD983 induced autophagic cell death using confocal microscopic examination, investigating the level of conversion of LC3-I to LC3-II and flow cytometric detection of AVO-positive cells. Taken together, the data suggest that KUD983 is an anticancer β-dipeptide against HRPCs through the inhibition of cell proliferation and induction of apoptotic and autophagic cell death. The suppression of signaling pathways mediated by c-Myc, PI3K/Akt and mTOR/p70S6K/4E-BP1 and the collaboration with down-regulation of Mcl-1 and survivin may indicate the mechanism of KUD983 against HRPC.

Keywords: β-dipeptide, hormone-refractory prostate cancer, mTOR, PI3K/Akt

Procedia PDF Downloads 251
886 Understanding the Information in Principal Component Analysis of Raman Spectroscopic Data during Healing of Subcritical Calvarial Defects

Authors: Rafay Ahmed, Condon Lau

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Bone healing is a complex and sequential process involving changes at the molecular level. Raman spectroscopy is a promising technique to study bone mineral and matrix environments simultaneously. In this study, subcritical calvarial defects are used to study bone composition during healing without discomposing the fracture. The model allowed to monitor the natural healing of bone avoiding mechanical harm to the callus. Calvarial defects were created using 1mm burr drill in the parietal bones of Sprague-Dawley rats (n=8) that served in vivo defects. After 7 days, their skulls were harvested after euthanizing. One additional defect per sample was created on the opposite parietal bone using same calvarial defect procedure to serve as control defect. Raman spectroscopy (785 nm) was established to investigate bone parameters of three different skull surfaces; in vivo defects, control defects and normal surface. Principal component analysis (PCA) was utilized for the data analysis and interpretation of Raman spectra and helped in the classification of groups. PCA was able to distinguish in vivo defects from normal surface and control defects. PC1 shows that the major variation at 958 cm⁻¹, which corresponds to ʋ1 phosphate mineral band. PC2 shows the major variation at 1448 cm⁻¹ which is the characteristic band of CH2 deformation and corresponds to collagens. Raman parameters, namely, mineral to matrix ratio and crystallinity was found significantly decreased in the in vivo defects compared to surface and controls. Scanning electron microscope and optical microscope images show the formation of newly generated matrix by means of bony bridges of collagens. Optical profiler shows that surface roughness increased by 30% from controls to in vivo defects after 7 days. These results agree with Raman assessment parameters and confirm the new collagen formation during healing.

Keywords: Raman spectroscopy, principal component analysis, calvarial defects, tissue characterization

Procedia PDF Downloads 196
885 Anti-Prostate Cancer Effect of GV-1001, a Novel Gonadotropin-Releasing Hormone Receptor Ligand

Authors: Ji Won Kim, Moo Yeol Lee, Keon Wook Kang

Abstract:

GV-1001, 16 amino acid fragment of human telomerase reverse transcriptase catalytic subunit (hTERT), has been developed as an injectable cancer vaccine for many types of solid tumors showing high-level of telomerase activity. In the present study, we evaluated the anti-cancer effect of GV-1001 on androgen-receptor-positive prostate cancer. Two signaling pathways, Gs-adenylate cyclase-cAMP and Gq-IP3-Ca2+ pathways play a central role in GnRH receptor (GnRHR)-mediated activities. We found that leuprolide acetate (LA) mainly acted on Gq-mediated Ca2+ signaling, while GV-1001 preferentially acted on cAMP signaling; and both the effects were counteracted by cetrorelix, a GnRHR antagonist. We further tested whether GV-1001 affects tumor growth of human prostate cancer cells in vivo. Prostate tumor xenografts were established using LNCap, androgen receptor-positive prostate cancer cells, and the nude mice bearing tumors were subcutaneously injected with GV-1001 (0.01, 0.1, 1, 10 microg/kg/day) and LA (0.01 microg/kg/day) for 2 weeks. GV-1001 (1 and 10 microg/kg/day) significantly inhibited tumor growth of LNCap xenografts. Interestingly, mRNA expression of MMP2 and MMP9 was significantly suppressed by GV-1001 injection, but not by LA administration. Boyden chamber assay revealed that GV-1001 potently inhibited cell migration of LNCap. Our finding suggests that GV-1001 as a novel GnRHR ligand, has anti-proliferative and anti-migratory effects on androgen receptor-positive prostate cancer cells.

Keywords: GV-1001, GnRH, hTERT, prostate cancer

Procedia PDF Downloads 331
884 Unravelling of the TOR Signaling Pathway in Human Fungal Pathogen Cryptococcus neoformans

Authors: Yee-Seul So, Guiseppe Ianiri, Alex Idnurm, Yong-Sun Bahn

Abstract:

Tor1 is a serine/threonine protein kinase that is widely conserved across eukaryotic species. Tor1 was first identified in Saccharomyces cerevisiae as a target of rapamycin (TOR). The TOR pathway has been implicated in regulating cellular responses to nutrients, proliferation, translation, transcription, autophagy, and ribosome biogenesis. Here we identified two homologues of S. cerevisiae Tor proteins, CNAG_06642 (Tor1) and CNAG_05220 (Tlk1, TOR-like kinase 1), in Cryptococcus neoformans causing a life-threatening fungal meningoencephalitis. Both Tor1 and Tlk1 have rapamycin-binding (RB) domains but Tlk1 has truncated RB form. To study the TOR-signaling pathway in the fungal pathogen, we attempt to construct the tor1Δ and tlk1Δ mutants and phenotypically analyze them. Although we failed to construct the tor1Δ mutant, we successfully construct the tlk1Δ mutant. The tlk1Δ mutant does not exhibit any discernable phenotypes, suggesting that Tlk1 is dispensable in C. neoformans. The essentiality of TOR1 is independently confirmed by constructing the TOR1 promoter replacement strain by using a copper transporter 4 (CTR4) promoter and the TOR1/tor1 heterozygous mutant in diploid C. neoformans strain background followed by sporulation analysis. To further analyze the function of Tor1, we construct TOR1 overexpression mutant using a constitutively active histone H3 in C. neoformans. We find that the Tor1 overexpression mutant is resistant to rapamycin but the tlk1Δ mutant does not exhibit any altered resistance to rapamycin, further confirming that Tor1, but not Tlk1, is critical for TOR signaling. Furthermore, we found that Tor1 is involved in response to diverse stresses, including genotoxic stress, oxidative stress, thermo-stress, antifungal drug treatment, and production of melanin. To identify any TOR-related transcription factors, we screened C. neoformans transcription factor library that we constructed in our previous study and identified several potential downstream factors of Tor1, including Atf1, Crg1 and Bzp3. In conclusion, the current study provides insight into the role of the TOR signaling pathway in human fungal pathogens as well as C. neoformans.

Keywords: fungal pathogen, serine/threonine kinase, target of rapamycin, transcription factor

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883 Influence of Ligature Tightening on Bone Fracture Risk in Interspinous Process Surgery

Authors: Dae Kyung Choi, Won Man Park, Kyungsoo Kim, Yoon Hyuk Kim

Abstract:

The interspinous process devices have been recently used due to its advantages such as minimal invasiveness and less subsidence of the implant to the osteoporotic bone. In this paper, we have analyzed the influences of ligature tightening of several interspinous process devices using finite element analysis. Four types of interspinous process implants were inserted to the L3-4 spinal motion segment based on their surgical protocols. Inferior plane of L4 vertebra was fixed and 7.5 Nm of extension moment were applied on superior plane of L3 vertebra with 400N of compressive load along follower load direction and pretension of the ligature. The stability of the spinal unit was high enough than that of intact model. The higher value of pretension in the ligature led the decrease of dynamic stabilization effect in cases of the WallisTM, DiamTM, Viking, and Spear®. The results of present study could be used to evaluate surgical option and validate the biomechanical characteristics of the spinal implants.

Keywords: interspinous process device, bone fracture risk, lumbar spine, finite element analysis

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882 Effects of Li2O Doping on Mechanical and Electrical Properties of Bovine Hydroxyapatite Composites (BHA)

Authors: Sibel Daglilar, Isil Kerti, Murat Karagoz, Fatih Dumludag, Oguzhan Gunduz, Faik Nuzhet Oktar

Abstract:

Hydroxyapatite (HA) materials have common use in bone repairing due to its ability to accelerate the bone growth around the implant. In spite of being a biocompatible and bioactive material, HA has a limited usage as an implant material because of its weak mechanical properties. HA based composites are required to improve the strength and toughness properties of the implant materials without compromising of biocompatibility. The excellent mechanical properties and higher biocompatibilities are expected from each of biomedical composites. In this study, HA composites were synthesized by using bovine bone reinforced doped with different amount of (wt.%) Li2O. The pressed pellets were sintered at various sintering temperatures between 1000ºC and 1300°C, and mechanical, electrical properties of the obtained products were characterized. In addition to that, in vitro stimulated body fluid (SBF) tests for these samples were conducted. The most suitable composite composition for biomedical applications was discussed among the composites studied.

Keywords: biocomposites, sintering temperature, biocompatibility, electrical property, conductivity, mechanical property

Procedia PDF Downloads 373
881 Osteitis in the Diabetic Foot in Algeria

Authors: Mohamed Amine Adaour, Mohamed Sadek Bachene, Mosaab Fortassi, Wafaa Siouda

Abstract:

— Foot infections are responsible for a significant number of hospitalizations and amputations in diabetic patients. The objective of our study is to analyze and evaluate the management of diabetic foot in a surgical setting. A retrospective study was conducted based on a selected case of suspected diabetic foot infections of osteitis treated at the Mohamed Boudiaf hospital in Medea.The case was reiterated as a therapeutic charge, consisting of treating first the infection of the soft tissues, then the osteitis: biopsy after at least 15 days of cessation of antibiotic therapy. Successful treatment of osteitis was defined at the end of a follow-up period of complete wound healing, lack of bone resection/amputation surgery at the initial bone site during follow-up , Instead, biopsies are prescribed in the treatment of soft tissue infection. The mean duration of treatment for soft tissue infection was 2-3 weeks, the duration of the antibiotic-free window of therapy prior to bone biopsy was 2-4 weeks. This patient received medical management without surgical resection. The success rate for treating osteitis at one year was 73%, and healing at one year was 88%.It is often limited to a sausage of the foot at the cost of repeated amputations. The best management remains prevention, which necessarily involves setting up a specialized and adapted centre.

Keywords: diabetic foot, bone biopsy, osteitis, algeria

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880 Tc-99m MIBI Scintigraphy to Differentiate Malignant from Benign Lesions, Detected on Planar Bone Scan

Authors: Aniqa Jabeen

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The aim of this study was to evaluate the effectiveness of Tc-99m MIBI (Technetium 99-methoxy-iso-butyl-isonitrile) scintigraphy to differentiate malignancies from benign lesions, which were detected on planar bone scans. Materials and Methods: 59 patients with bone lesions were enrolled in the study. The scintigraphic findings were compared with the clinical, radiological and the histological findings. Each patient initially underwent a three-phase bone scan with Tc-99m MDP (Methylene Diphosphonate) and if evidence of lesion found, the patient then underwent a dynamic and static MIBI scintigraphy after three to four days. The MDP and MIBI scans were evaluated visually and quantitatively. For quantitative analysis count ratios of lesions and contralateral normal side (L/C) were taken by region of interests drawn on scans. The Student T test was applied to assess the significant difference between benign and malignant lesions p-value < 0.05 was considered significant. Result: The MDP scans showed the increase tracer uptake, but there was no significant difference between benign and malignant uptake of the radiotracer. However significant difference (p-value 0.015), in uptake was seen in malignant (L/C = 3.51 ± 1.02) and benign lesion (L/C = 2.50±0.42) on MIBI scan. Three of thirty benign lesions did not show significant MIBI uptake. Seven malignant appeared as false negatives. Specificity of the scan was 86.66%, and its Negative Predictive Value (NPV) was 81.25% whereas the sensitivity of scan was 79.31%. In excluding the axial metastasis from the lesions, the sensitivity of MIBI scan increased to 91.66% and the NPV also increased to 92.85%. Conclusion: MIBI scintigraphy provides its usefulness by distinguishing malignant from benign lesions. MIBI also correctly identifies metastatic lesions. The negative predictive value of the scan points towards its ability to accurately diagnose the normal (benign) cases. However, biopsy remains the gold standard and a definitive diagnostic modality in musculoskeletal tumors. MIBI scan provides useful information in preoperative assessment and in distinguishing between malignant and benign lesions.

Keywords: benign, malignancies, MDP bone scan, MIBI scintigraphy

Procedia PDF Downloads 373
879 Physiopathology of Osteitis in the Diabetic Foot

Authors: Mohamed Amine Adaour, Mohamed Sadek Bachene, Mosaab Fortassi, Wafaa Siouda

Abstract:

Foot infections are responsible for a significant number of hospitalizations and amputations in diabetic patients. The objective of our study is to analyze and evaluate the management of diabetic foot in a surgical setting. A retrospective study was conducted based on a selected case of suspected diabetic foot infections of osteitis treated at the Mohamed Boudiaf hospital in Medea. The case was reiterated as a therapeutic charge, consisting of treating first the infection of the soft tissues, then the osteitis: biopsy after at least 15 days of cessation of antibiotic therapy. Successful treatment of osteitis was defined at the end of a follow-up period of complete wound healing, lack of bone resection/amputation surgery at the initial bone site during follow-up , Instead, biopsies are prescribed in the treatment of soft tissue infection. The mean duration of treatment for soft tissue infection was 2-3 weeks, the duration of the antibiotic-free window of therapy prior to bone biopsy was 2-4 weeks. This patient received medical management without surgical resection. The success rate for treating osteitis at one year was 73%, and healing at one year was 88%.It is often limited to a sausage of the foot at the cost of repeated amputations. The best management remains prevention, which necessarily involves setting up a specialized and adapted centre.

Keywords: osteitis, antibiotic therapy, bone biopsy, diabetic foot

Procedia PDF Downloads 57