Search results for: mice bone
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1270

Search results for: mice bone

700 Finite Element Analysis of Dental Implant for Prosthesis

Authors: Mayur Chaudhari, Ashutosh Gaikwad, Shubham Kavathale, Aditya Mule, Dilip Panchal, Puja Verma

Abstract:

The purpose of this investigation was to locate restorative bio-materials for the manufacture of implants and crowns. A three-dimensional (3D) finite element analysis (FEA) was carried out to evaluate the stress distribution in the implant and abutment with several types of bio-materials and various prosthetic crowns. While the dental implant, abutment, and screw were subjected to a vertical impact force, the effects of mechanical characteristics such as Young's modulus and Poisson's ratio were evaluated and contrasted. Crowns are made from zirconia, cobalt, ceramic, acrylic resin, and porcelain materials. Implants are made from materials such as titanium, zirconia, PEEK, and CFR-PEEK. SolidWorks was used to create the 3D geometry, and Ansys Software was used to analyze it. The results show that using CFR-PEEK implants and an acrylic resin crown resulted in less bone stress than using alternative materials. In order to reduce the amount of stress on the bone and possibly prevent implant failure, the study's findings support the use of a CFR PEEK implant, abutment, and crown in bruxism patients.

Keywords: biomaterials, implant, crown, abutment

Procedia PDF Downloads 40
699 Piezosurgery in Periodontics and Oral Implantology

Authors: Neelesh Papineni

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Aim: Piezosurgery is a relatively new technique for osteotomy and osteoplasty that uses ultrasonic vibration. The conventional method of treating periodontal cases are by conventional surgeries. However, in this advancing field the use of motor-driven instruments is being considered less invasive. Out of these motor-driven instruments, piezo-electric device has been introduced to the field of periodontics and oral implantology. This article discusses about the wide range of application of piezo-electric device in periodontology, its advantages over conventional surgical therapies and other motor-driven instruments. Results: Piezo- electric has shown better results in aspect of osteotomy, osteoplasty, implants, and any procedure which includes conserving the bone. Also piezo-electric does not cause any kind of damage to the surrounding soft tissue and eliminates the risk of bone necrosis which is a risk factor in other motor driven instruments. Conclusion: In this era of modern dentistry , a successful periodontal and implant surgery requires a sound osseous support. This review gives a pictorial representation about the wide range of application of piezo-electric device in periodontology.

Keywords: piezo-electric, osteotomy, osteoplasty, implantology

Procedia PDF Downloads 359
698 Alveolar Ridge Preservation in Post-extraction Sockets Using Concentrated Growth Factors: A Split-Mouth, Randomized, Controlled Clinical Trial

Authors: Sadam Elayah

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Background: One of the most critical competencies in advanced dentistry is alveolar ridge preservation after exodontia. The aim of this clinical trial was to assess the impact of autologous concentrated growth factor (CGF) as a socket-filling material and its ridge preservation properties following the lower third molar extraction. Materials and Methods: A total of 60 sides of 30 participants who had completely symmetrical bilateral impacted lower third molars were enrolled. The short-term outcome variables were wound healing, swelling and pain, clinically assessed at different time intervals (1st, 3rd & 7th days). While the long-term outcome variables were bone height & width, bone density and socket surface area in the coronal section. Cone beam computed tomography images were obtained immediately after surgery and three months after surgery as a temporal measure. Randomization was achieved by opaque, sealed envelopes. Follow-up data were compared to baseline using Paired & Unpaired t-tests. Results: The wound healing index was significantly better in the test sides (P =0.001). Regarding the facial swelling, the test sides had significantly fewer values than the control sides, particularly on the 1st (1.01±.57 vs 1.55 ±.56) and 3rd days (1.42±0.8 vs 2.63±1.2) postoperatively. Nonetheless, the swelling disappeared within the 7th day on both sides. The pain scores of the visual analog scale were not a statistically significant difference between both sides on the 1st day; meanwhile, the pain scores were significantly lower on the test sides compared with the control sides, especially on the 3rd (P=0.001) and 7th days (P˂0.001) postoperatively. Regarding long-term outcomes, CGF sites had higher values in height and width when compared to Control sites (Buccal wall 32.9±3.5 vs 29.4±4.3 mm, Lingual wall 25.4±3.5 vs 23.1±4 mm, and Alveolar bone width 21.07±1.55vs19.53±1.90 mm) respectively. Bone density showed significantly higher values in CGF sites than in control sites (Coronal half 200±127.3 vs -84.1±121.3, Apical half 406.5±103 vs 64.2±158.6) respectively. There was a significant difference between both sites in reducing periodontal pockets. Conclusion: CGF application following surgical extraction provides an easy, low-cost, and efficient option for alveolar ridge preservation. Thus, dentists may encourage using CGF during dental extractions, particularly when alveolar ridge preservation is required.

Keywords: platelet, extraction, impacted teeth, alveolar ridge, regeneration, CGF

Procedia PDF Downloads 49
697 Gut Microbial Dynamics in a Mouse Model of Inflammation-Linked Carcinogenesis as a Result of Diet Supplementation with Specific Mushroom Extracts

Authors: Alvarez M., Chapela M. J., Balboa E., Rubianes D., Sinde E., Fernandez de Ana C., Rodríguez-Blanco A.

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The gut microbiota plays an important role as gut inflammation could contribute to colorectal cancer development; however, this role is still not fully understood, and tools able to prevent this progression are yet to be developed. The main objective of this study was to monitor the effects of a mushroom extracts formulation in gut microbial community composition of an Azoxymethane (AOM)/Dextran sodium sulfate (DSS) mice model of inflammation-linked carcinogenesis. For the in vivo study, 41 adult male mice of the C57BL / 6 strain were obtained. 36 of them have been induced in a state of colon carcinogenesis by a single intraperitoneal administration of AOM at a dose of 12.5 mg/kg; the control group animals received instead of the same volume of 0.9% saline. DSS is an extremely toxic polysaccharide sulfate that causes chronic inflammation of the colon mucosa, favoring the appearance of severe colitis and the production of tumors induced by AOM. Induction by AOM/DSS is an interesting platform for chemopreventive intervention studies. This time the model was used to monitor gut microbiota changes as a result of supplementation with a specific mushroom extracts formulation previously shown to have prebiotic activity. The animals have been divided into three groups: (i) Cancer + mushroom extracts formulation experimental group: to which the MicoDigest2.0 mushroom extracts formulation developed by Hifas da Terra S.L has been administered dissolved in drinking water at an estimated concentration of 100 mg / ml. (ii) Control group of animals with Cancer: to which normal water has been administered without any type of treatment. (iii) Control group of healthy animals: these are the animals that have not been induced cancer or have not received any treatment in drinking water. This treatment has been maintained for a period of 3 months, after which the animals were sacrificed to obtain tissues that were subsequently analyzed to verify the effects of the mushroom extract formulation. A microbiological analysis has been carried out to compare the microbial communities present in the intestines of the mice belonging to each of the study groups. For this, the methodology of massive sequencing by molecular analysis of the 16S gene has been used (Ion Torrent technology). Initially, DNA extraction and metagenomics libraries were prepared using the 16S Metagenomics kit, always following the manufacturer's instructions. This kit amplifies 7 of the 9 hypervariable regions of the 16S gene that will then be sequenced. Finally, the data obtained will be compared with a database that makes it possible to determine the degree of similarity of the sequences obtained with a wide range of bacterial genomes. Results obtained showed that, similarly to certain natural compounds preventing colorectal tumorigenesis, a mushroom formulation enriched the Firmicutes and Proteobacteria phyla and depleted Bacteroidetes. Therefore, it was demonstrated that the consumption of the mushroom extracts’ formulation developed could promote the recovery of the microbial balance that is disrupted in the mice model of carcinogenesis. More preclinical and clinical studies are needed to validate this promising approach.

Keywords: carcinogenesis, microbiota, mushroom extracts, inflammation

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696 The Combination of Curcuma Extract and IgG Colostrum on Strongyloides Infection in CD1 Mice

Authors: Laurentius J. M. Rumokoy, Jimmy Posangi, Wisje Lusia Toar, Julio Lopez Aban

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The threat of pathogen infection agents to the neonates is a major health problem to the new born life livestock. Neonate losses became an important case in the world as well as in Indonesia. This condition can be triggered by an infection with nematode in conjunction with a failure of immunoglobulin passive transfer. The study was conducted to evaluate the role of the curcuma combined with IgG colostrum on the development of parasites in the gut of CD1 mice. Animal experiments were divided in four groups (G) based on the treatment: G1 (infection only); G2 (curcuma+infection), G3 (IgG + infection) and G4 (curcuma+IgG+infection). The parameters measured were EPG (eggs per gram) and female in the intestine. The results obtained showed that the treatment has no a significant influence on the number of eggs per gram of feces in the group infected compared to the control group without receiving IgG nor curcuma. However, the EGP response tended to decrease at day 6 in G3 and G4 with a minimum number at zero eggs. This performant showed that the immunoglobulin-G and curcuma substances could slightly decreased the number of eggs in animal infected with Strongyloides. The results obtained showed also that the treatment has no significant difference (P > 0.05) on female larva in the gut of MCD1 experimental. In other side, we found that the best performance to inhibit the female quantity in the gut was the treatment with IgG and infection of parasite in G3. In this treatment, the minimum number was five female only in the gut. The results described IgG response was better than the curcuma single use in reducing the female parasite in the gut. This positive response of IgG compared to other controls group was associated with the function of colostrum antibodies.

Keywords: parasites, livestock, curcuma, colostrums

Procedia PDF Downloads 155
695 Local Treatment of Metastatic Squamous Cell Carcinoma of The Mandible Using for the First Time Cryosurgery

Authors: Wahid Terro, Miray Terro, Franco Lugnani

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Roughly 90% of mouth cancer is squamous cell carcinoma. Oral region metastases are considered uncommon. The most frequent sources of metastatic tumors to the mouth are primary cancers from the lung and breast with the latter being the most common site for tumors that metastasize to the jawbones. Treatment involves surgery, radiation, chemotherapy, or a combination of these. However, these treatment modalities entail severe aesthetic and functional side effects. This article aims to present an alternative and unprecedented treatment modality for metastatic mandibular bone carcinoma – Cryosurgery. A 37-year-old female patient presented with gradually increasing pain over several weeks whose radiological tests revealed a formation of mass in the left mandibular ramus. A biopsy obtained by bone puncture of the ramus was reported to be metastatic breast squamous cell carcinoma. The patient has been successfully treated without esthetic and functional side effects by using for the first-time worldwide cryosurgery. We conclude that it is value promoting this method for current and future use.

Keywords: carcinoma, mandible, metastasis, breast

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694 Unidentified Remains with Extensive Bone Disease without a Clear Diagnosis

Authors: Patricia Shirley Almeida Prado, Selma Paixão Argollo, Maria De Fátima Teixeira Guimarães, Leticia Matos Sobrinho

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Skeletal differential diagnosis is essential in forensic anthropology in order to differentiate skeletal trauma from normal osseous variation and pathological processes. Thus, part of forensic anthropological field is differentiate skeletal criminal injuries from the normal skeletal variation (bone fusion or nonunion, transitional vertebrae and other non-metric traits), non-traumatic skeletal pathology (myositis ossificans, arthritis, bone metastasis, osteomyelitis) from traumatic skeletal pathology (myositis ossificans traumatic) avoiding misdiagnosis. This case shows the importance of effective pathological diagnosis in order to accelerate the identification process of skeletonized human remains. THE CASE: An unidentified skeletal remains at the medico legal institute Nina Rodrigues-Salvador, of a male young adult (29 to 40 years estimated) showing a massive heterotopic ossification on its right tibia at upper epiphysis and adjacent articular femur surface; an extensive ossification on the right clavicle (at the sternal extremity) also presenting an heterotopic ossification at right scapulae (upper third of scapulae lateral margin and infraglenoid tubercule) and at the head of right humerus at the shoulder joint area. Curiously, this case also shows an unusual porosity in certain vertebrae´s body and in some tarsal and carpal bones. Likewise, his left fifth metacarpal bones (right and left) showed a healed fracture which led both bones distorted. Based on identification, of pathological conditions in human skeletal remains literature and protocols these alterations can be misdiagnosed and this skeleton may present more than one pathological process. The anthropological forensic lab at Medico-legal Institute Nina Rodrigues in Salvador (Brazil) adopts international protocols to ancestry, sex, age and stature estimations, also implemented well-established conventions to identify pathological disease and skeletal alterations. The most compatible diagnosis for this case is hematogenous osteomyelitis due to following findings: 1: the healed fracture pattern at the clavicle showing a cloaca which is a pathognomonic for osteomyelitis; 2: the metacarpals healed fracture does not present cloaca although they developed a periosteal formation. 3: the superior articular surface of the right tibia shows an extensive inflammatory healing process that extends to adjacent femur articular surface showing some cloaca at tibia bone disease. 4: the uncommon porosities may result from hematogenous infectious process. The fractures probably have occurred in a different moments based on the healing process; the tibia injury is more extensive and has not been reorganized, while metacarpals and clavicle fracture is properly healed. We suggest that the clavicle and tibia´s fractures were infected by an existing infectious disease (syphilis, tuberculosis, brucellosis) or an existing syndrome (Gorham’s disease), which led to the development of osteomyelitis. This hypothesis is supported by the fact that different bones are affected in diverse levels. Like the metacarpals that do not show the cloaca, but then a periosteal new bone formation; then the unusual porosities do not show a classical osteoarthritic processes findings as the marginal osteophyte, pitting and new bone formation, they just show an erosive process without bone formation or osteophyte. To confirm and prove our hypothesis we are working on different clinical approaches like DNA, histopathology and other image exams to find the correct diagnostic.

Keywords: bone disease, forensic anthropology, hematogenous osteomyelitis, human identification, human remains

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693 Layer-by-Layer Coated Dexamethasone Microcrystals for Experimental Inflammatory Bowel Disease Therapy

Authors: Murtada Ahmed Oshi, Jin-Wook Yoo

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Layer-by-layer (LBL) coating has gained popularity for drug delivery of therapeutic drugs. Herein we described a novel approach for enhancing the therapeutic efficiency of the locally administered dexamethasone (Dex) for inflammatory bowel disease (IBD). We utilized a LBL-coating technique on Dex microcrystals (DexMCs) with multiple layers of polyelectrolytes composed of poly (allylamine hydrochloride) (PAH), poly (sodium 4-styrene sulfonate) (PSS) and Eudragit® S100 (ES). The successful deposition of the layers onto DexMCs surfaces were confirmed through zeta potential measurement and confocal laser scanning microscopy. The surface morphology was investigated through scanning electron microscopy. The drug encapsulation efficiency was 95% with a mean particle size of 2 µm and negative surface charge (-40 mV). Moreover, in vitro drug release study showed a minimum release of the drug ( 15%) at an acidic condition during initial first 5 h, followed by sustained-release at an alkaline condition. For in vivo study, LBL-DxMCs were administered orally to ICR mice suffering from dextran sulfate sodium-induced colitis. LBL-DxMCs substantially enhanced anti-IBD activities as compared to DxMCs. Macroscopic, histological and biochemical (tumor necrosis factor-α, interleukin-6 and myeloperoxidase) examinations revealed marked improvements of colitis signs in the mice treated with LBL-DxMCs compared with those treated with DxMCs. Overall, LBL-DxMCs could be a suitable candidate for the treatment of IBD.

Keywords: dexamethasone, inflammatory bowel disease, LBL-coating, polyelectrolytes

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692 In silico Designing and Insight into Antimalarial Potential of Chalcone-Quinolinylpyrazole Hybrids by Preclinical Study in Mice

Authors: Deepika Saini, Sandeep Jain, Ajay Kumar

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The quinoline scaffold is one of the most widely studied in the discovery of derivatives with various heterocyclic moieties due to its potential antimalarial activities. In the present study, a chalcone series of quinoline derivatives clubbed with pyrazole were synthesized to evaluate their antimalarial property by in vitro schizont maturation inhibition assay against both chloroquine sensitive, 3D7 and chloroquine resistant, RKL9 strain of Plasmodium falciparum. Further, top five compounds were studied for in vivo preclinical study for antimalarial potential against P. berghei in Swiss albino mice. To understand the mechanism of synthesized analogues, they were screened computationally by molecular docking techniques. Compounds were docked into the active site of a protein receptor, Plasmodium falciparum Cysteine Protease Falcipain-2. The compounds were successfully synthesized, and structural confirmation was performed by FTIR, 1H-NMR, mass spectrometry and elemental analysis. In vitro study suggested that the compounds 5b, 5g, 5l, 5s and 5u possessed best antimalarial activity and further tested for in vivo screening. Compound 5u (CH₃ on both rings) with EC₅₀ 0.313 & 0.801 µg/ml against CQ-S & CQ-R strains of P. falciparum respectively and 78.01% suppression of parasitemia. The molecular docking studies of the compounds helped in understanding the mechanism of action against falcipain-2. The present study reveals the binding signatures of the synthesized ligands within the active site of the protein, and it explains the results from in vitro study in their EC₅₀ values and percentage parasitemia.

Keywords: antimalarial activity, chalcone, docking, quinoline

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691 Production, Characterisation, and in vitro Degradation and Biocompatibility of a Solvent-Free Polylactic-Acid/Hydroxyapatite Composite for 3D-Printed Maxillofacial Bone-Regeneration Implants

Authors: Carlos Amnael Orozco-Diaz, Robert David Moorehead, Gwendolen Reilly, Fiona Gilchrist, Cheryl Ann Miller

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The current gold-standard for maxillofacial reconstruction surgery (MRS) utilizes auto-grafted cancellous bone as a filler. This study was aimed towards developing a polylactic-acid/hydroxyapatite (PLA-HA) composite suitable for fused-deposition 3D printing. Functionalization of the polymer through the addition of HA was directed to promoting bone-regeneration properties so that the material can rival the performance of cancellous bone grafts in terms of bone-lesion repair. This kind of composite enables the production of MRS implants based off 3D-reconstructions from image studies – namely computed tomography – for anatomically-correct fitting. The present study encompassed in-vitro degradation and in-vitro biocompatibility profiling for 3D-printed PLA and PLA-HA composites. PLA filament (Verbatim Co.) and Captal S hydroxyapatite micro-scale HA powder (Plasma Biotal Ltd) were used to produce PLA-HA composites at 5, 10, and 20%-by-weight HA concentration. These were extruded into 3D-printing filament, and processed in a BFB-3000 3D-Printer (3D Systems Co.) into tensile specimens, and were mechanically challenged as per ASTM D638-03. Furthermore, tensile specimens were subjected to accelerated degradation in phosphate-buffered saline solution at 70°C for 23 days, as per ISO-10993-13-2010. This included monitoring of mass loss (through dry-weighing), crystallinity (through thermogravimetric analysis/differential thermal analysis), molecular weight (through gel-permeation chromatography), and tensile strength. In-vitro biocompatibility analysis included cell-viability and extracellular matrix deposition, which were performed both on flat surfaces and on 3D-constructs – both produced through 3D-printing. Discs of 1 cm in diameter and cubic 3D-meshes of 1 cm3 were 3D printed in PLA and PLA-HA composites (n = 6). The samples were seeded with 5000 MG-63 osteosarcoma-like cells, with cell viability extrapolated throughout 21 days via resazurin reduction assays. As evidence of osteogenicity, collagen and calcium deposition were indirectly estimated through Sirius Red staining and Alizarin Red staining respectively. Results have shown that 3D printed PLA loses structural integrity as early as the first day of accelerated degradation, which was significantly faster than the literature suggests. This was reflected in the loss of tensile strength down to untestable brittleness. During degradation, mass loss, molecular weight, and crystallinity behaved similarly to results found in similar studies for PLA. All composite versions and pure PLA were found to perform equivalent to tissue-culture plastic (TCP) in supporting the seeded-cell population. Significant differences (p = 0.05) were found on collagen deposition for higher HA concentrations, with composite samples performing better than pure PLA and TCP. Additionally, per-cell-calcium deposition on the 3D-meshes was significantly lower when comparing 3D-meshes to discs of the same material (p = 0.05). These results support the idea that 3D-printable PLA-HA composites are a viable resorbable material for artificial grafts for bone-regeneration. Degradation data suggests that 3D-printing of these materials – as opposed to other manufacturing methods – might result in faster resorption than currently-used PLA implants.

Keywords: bone regeneration implants, 3D-printing, in vitro testing, biocompatibility, polymer degradation, polymer-ceramic composites

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690 Inhibitory Effect of Lactic Acid Bacteria on Uropathogenic Escherichia coli-Induced Urinary Tract Infections

Authors: Cheng-Chih Tsai, Yu-Hsuan Liu, Cheng-Ying Ho, Chun-Chin Huang

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The aim of this study evaluated the in vitro and in vivo antimicrobial activity of selected lactic acid bacteria (LAB) against Uropathogenic Escherichia coli (UPEC) for prevention and amelioration of UTIs. We screened LAB strains with antimicrobial effects on UPEC using a well-diffusion assay, bacterial adherence to the uroepithelium cell line SV-HUC-1 (BCRC 60358), and a coculture inhibition assay. The results showed that the 7 LAB strains (Lactobacillus paracasei, L. salivarius, two Pediococcus pentosaceus strains, two L. plantarum strains, and L. crispatus) and the fermented probiotic products produced by these multi-LAB strains exhibited potent zones of inhibition against UPEC. Moreover, the LAB strains and probiotic products adhered strongly to the uroepithelium SV-HUC-1 cell line. The growth of UPEC strains was also markedly inhibited after co-culture with the LAB strains and probiotic products in human urine. In addition, the enhanced levels of IL-6, IL-8 and lactic acid dehydrogenase were significantly decreased by treatments with the LAB strains and probiotic products in UPEC-induced SV-HUC-1 cells. Furthermore, oral administration of probiotic products reduced the number of viable UPEC in the urine of UPEC-challenged BALB/c mice. Taken together, this study demonstrates that probiotic supplementation may be useful as an adjuvant therapy for the treatment of bacterial-induced urinary tract infections.

Keywords: lactic acid bacterium, SV-HUC-1 uroepithelium, urinary tract infection, uropathogenic Escherichia coli, BALB/c mice

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689 Allium Cepa Extract Provides Neuroprotection Against Ischemia Reperfusion Induced Cognitive Dysfunction and Brain Damage in Mice

Authors: Jaspal Rana, Alkem Laboratories, Baddi, Himachal Pradesh, India Chitkara University, Punjab, India

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Oxidative stress has been identified as an underlying cause of ischemia-reperfusion (IR) related cognitive dysfunction and brain damage. Therefore, antioxidant based therapies to treat IR injury are being investigated. Allium cepa L. (onion) is used as culinary medicine and is documented to have marked antioxidant effects. Hence, the present study was designed to evaluate the effect of A. cepa outer scale extract (ACE) against IR induced cognition and biochemical deficit in mice. ACE was prepared by maceration with 70% methanol and fractionated into ethylacetate and aqueous fractions. Bilateral common carotid artery occlusion for 10 min followed by 24 h reperfusion was used to induce cerebral IR injury. Following IR injury, ACE (100 and 200 mg/kg) was administered orally to animals for 7 days once daily. Behavioral outcomes (memory and sensorimotor functions) were evaluated using Morris water maze and neurological severity score. Cerebral infarct size, brain thiobarbituric acid reactive species, reduced glutathione, and superoxide dismutase activity was also determined. Treatment with ACE significantly ameliorated IR mediated deterioration of memory and sensorimotor functions and rise in brain oxidative stress in animals. The results of the present investigation revealed that ACE improved functional outcomes after cerebral IR injury, which may be attributed to its antioxidant properties.

Keywords: stroke, neuroprotection, ischemia reperfusion, herbal drugs

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688 Neuropharmacological and Neurochemical Evaluation of Methanolic Extract of Elaeocarpus sphaericus (Gaertn.) Stem Bark by Using Multiple Behaviour Models of Mice

Authors: Jaspreet Kaur, Parminder Nain, Vipin Saini, Sumitra Dahiya

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Elaeocarpus sphaericus has been traditionally used in the Indian traditional medicine system for the treatment of stress, anxiety, depression, palpitation, epilepsy, migraine and lack of concentration. The study was investigated to evaluate the neurological potential such as anxiolytic, muscle relaxant and sedative activity of methanolic extract of Elaeocarpus sphaericus stem bark (MEESSB) in mice. Preliminary phytochemical screening and acute oral toxicity of MEESSB was carried out by using standard methods. The anxiety was induced by employing Elevated Plus-Maze (EPM), Light and Dark Test (LDT), Open Field Test (OFT) and Social Interaction test (SIT). The motor coordination and sedative effect was also observed by using actophotometer, rota-rod apparatus and ketamine-induced sleeping time, respectively. Animals were treated with different doses of MEESSB (i.e.100, 200, 400 and 800 mg/kg orally) and diazepam (2 mg/kg i.p) for 21 days. Brain neurotransmitters like dopamine, serotonin and nor-epinephrine level were estimated by validated methods. Preliminary phytochemical analysis of the extract revealed the presence of tannins, phytosterols, steroids and alkaloids. In the acute toxicity studies, MEESSB was found to be non-toxic and with no mortality. In anxiolytic studies, the different doses of MEESSB showed a significant (p<0.05) effect on EPM and LDT. In OFT and SIT, a significant (p<0.05) increase in ambulation, rearing and social interaction time was observed. In the case of motor coordination activity, the MEESSB does not cause any significant effect on the latency to fall off from the rotarod bar as compared to the control group. Moreover, no significant effects on ketamine-induced sleep latency and total sleeping time induced by ketamine were observed. Results of neurotransmitter estimation revealed the increased concentration of dopamine, whereas the level of serotonin and nor-epinephrine was found to be decreased in the mice brain, with MEESSB at dose 800 mg/kg only. The study has validated the folkloric use of the plant as an anxiolytic in Indian traditional medicine while also suggesting potential usefulness in the treatment of stress and anxiety without causing sedation.

Keywords: anxiolytic, behavior experiments, brain neurotransmitters, elaeocarpus sphaericus

Procedia PDF Downloads 159
687 Antioxidant Defense Mechanisms in Murine Epidermis and Dermis and Their Responses to Ultraviolet Light

Authors: Ben Abderrahmane Ayoub El Fateh, Bnina Rachid

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A comprehensive comparison of antioxidant defenses in the dermis and epidermis and their response to exposure to ultraviolet (UV) irradiation has not previously been attempted. In this study, enzymic and non-enzymic antioxidants in epidermis and dermis of hairless mice were compared. Enzyme activities are presented both as units/gram of skin and units/milligram of protein; arguments are presented for the superiority of skin wet weight as a reference base. Catalase, glutathione peroxidase, and glutathione reductase (units/gram of skin) were higher in the epidermis than dermis by 49%, 86%, and 74%, respectively. Superoxide dismutase did not follow this pattern. Lipophilic antioxidants ( -tocopherol, ubiquinol 9, and ubiquinone 9) and hydrophilic antioxidants (ascorbic acid, dehydroascorbic acid, and glutathione) were 24–95% higher in the epidermis than in dermis. In contrast, oxidized glutathione was 60% lower in the epidermis than in dermis. Mice were irradiated with solar light to examine the response of these cutaneous layers to UV irradiation. After irradiation with 25 J/cm2 (UVA + UVB, from a solar simulator), 10 times the minimum erythemal dose, epidermal and dermal catalase and superoxide dismutase activities were greatly decreased. Tocopherol, ubiquinol 9, ubiquinone 9, ascorbic acid, dehydroascorbic acid, and reduced glutathione decreased in both epidermis and dermis by 26-93%. Oxidizedgiutathione showed a slight, non-significant increase. Because the reduction in total ascorbate and catalase was much more severe in the epidermis than dermis, it can be concluded that UV light is more damaging to the antioxidant defenses in the epidermis than in the dermis.

Keywords: antioxidant defenses, enzymic, epidermis, oxidizedgiutathione

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686 Improval of Fracture Healing of Osteoporotic Bone by Lovastatin-Incorporated Poly-(DL-Lactide)

Authors: Nurul Izzah Ibrahim, Isa Naina Mohamed, Norazlina Mohamed, Ahmad Nazrun Shuid

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Osteoporosis disease delays fracture healing. Statins have shown potential for osteoporosis and to promote fracture healing. The effects of statin can be further potentiated by combining it with a carrier known as poly-(DL-lactide), which would provide persistent release of statin to the fracture site. This study was designed to investigate the effects of direct injection of poly-(DL-lactide)-incorporated lovastatin on fracture healing of postmenopausal osteoporosis rat model. Twenty-four Sprague-Dawley female rats were divided into 3 groups: sham-operated (SO), ovariectomized-control rats (OVxC) and poly-(DL-lactide)-incorporated lovastatin (OVx+Lov) groups. The OVx+Lov group was given a single injection of 750 µg/kg lovastatin particles incorporated with poly-(DL-lactide). After 4 weeks, the fractured tibiae were dissected out for biomechanical assessments of the callus. The OVx+Lov group showed significantly better callus strength than the OVxC group (p<0.05). In conclusion, a single injection of lovastatin-incorporated poly-(DL-lactide) was able to promote better fracture healing of osteoporotic bone.

Keywords: statins, fracture healing, osteoporosis, poly-(DL-lactide)

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685 Molecular Docking and Synthesis of Nitrogen-Containing Bisphosphonates

Authors: S. Ghalem, M. Mesmoudi, I. Daoudand, H. Allali

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The nitrogen-containing bisphosphonates (N-BPs) are well established as the treatments of choice for disorders of excessive bone resorption, myeloma and bone metastases, and osteoporosis. They inhibit farnesyl pyrophosphate synthase (FFPS), a key enzyme in the mevalonate pathway, resulting in inhibition of the prenylation of small GTP-binding proteins in osteoclasts and disruption of their cytoskeleton, adhesion/spreading, and invasion of cancer cells. A very few examples for synthesis of α-amino bisphosphonates based on several amino acids are known from the literature. In the present work, esters of aminoacid react with ketophsophonate (or their analog acid or acyl) to afford the desired products, α-iminophosphonates. The reaction of imine with dimethyl phosphate in the presence of catalytic amount of I2 give ester of α-aminobisphosphonate as sole product in good yield. Finally, we used computational docking methods to predict how several α-aminobisphosphonates bind to FPPS and how R and X influence. Pamidronate, β-aminobisphosphonate already marketed, was used as reference. These results are of interest since they represent a new and simple way to sythesize α-aminobisphosphonates with a free COOH group increased by R2 functionalisable and opening up the possibility of using the molecular docking to facilitate the design of other, novel FFPS inhibitors.

Keywords: drug research, cancer, α-amino bisphosphonates, molecular docking

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684 The Role of a Biphasic Implant Based on a Bioactive Silk Fibroin for Osteochondral Tissue Regeneration

Authors: Lizeth Fuentes-Mera, Vanessa Perez-Silos, Nidia K. Moncada-Saucedo, Alejandro Garcia-Ruiz, Alberto Camacho, Jorge Lara-Arias, Ivan Marino-Martinez, Victor Romero-Diaz, Adolfo Soto-Dominguez, Humberto Rodriguez-Rocha, Hang Lin, Victor Pena-Martinez

Abstract:

Biphasic scaffolds in cartilage tissue engineering have been designed to influence not only the recapitulation of the osteochondral architecture but also to take advantage of the healing ability of bone to promote the implant integration with the surrounding tissue and then bone restoration and cartilage regeneration. This study reports the development and characterization of a biphasic scaffold based on the assembly of a cartilage phase constituted by fibroin biofunctionalized with bovine cartilage matrix; cellularized with differentiated pre-chondrocytes from adipose tissue stem cells (autologous) and well attached to a bone phase (bone bovine decellularized) to mimic the structure of the nature of native tissue and to promote the cartilage regeneration in a model of joint damage in pigs. Biphasic scaffolds were assembled by fibroin crystallization with methanol. The histological and ultrastructural architectures were evaluated by optical and scanning electron microscopy respectively. Mechanical tests were conducted to evaluate Young's modulus of the implant. For the biological evaluation, pre-chondrocytes were loaded onto the scaffolds and cellular adhesion, proliferation, and gene expression analysis of cartilage extracellular matrix components was performed. The scaffolds that were cellularized and matured for 10 days were implanted into critical 3 mm in diameter and 9-mm in depth osteochondral defects in a porcine model (n=4). Three treatments were applied per knee: Group 1: monophasic cellular scaffold (MS) (single chondral phase), group 2: biphasic scaffold, cellularized only in the chondral phase (BS1), group 3: BS cellularized in both bone and chondral phases (BS2). Simultaneously, a control without treatment was evaluated. After 4 weeks of surgery, integration and regeneration tissues were analyzed by x-rays, histology and immunohistochemistry evaluation. The mechanical assessment showed that the acellular biphasic composites exhibited Young's modulus of 805.01 kPa similar to native cartilage (400-800 kPa). In vitro biological studies revealed the chondroinductive ability of the biphasic implant, evidenced by an increase in sulfated glycosaminoglycan (GAGs) and type II collagen, both secreted by the chondrocytes cultured on the scaffold during 28 days. No evidence of adverse or inflammatory reactions was observed in the in vivo trial; however, In group 1, the defects were not reconstructed. In group 2 and 3 a good integration of the implant with the surrounding tissue was observed. Defects in group 2 were fulfilled by hyaline cartilage and normal bone. Group 3 defects showed fibrous repair tissue. In conclusion; our findings demonstrated the efficacy of biphasic and bioactive scaffold based on silk fibroin, which entwined chondroinductive features and biomechanical capability with appropriate integration with the surrounding tissue, representing a promising alternative for osteochondral tissue-engineering applications.

Keywords: biphasic scaffold, extracellular cartilage matrix, silk fibroin, osteochondral tissue engineering

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683 Magnitude of Infection and Associated factor in Open Tibial Fractures Treated Operatively at Addis Ababa Burn Emergency and Trauma Center April, 2023

Authors: Tuji Mohammed Sani

Abstract:

Back ground: An open tibial fracture is an injury where the fractured bone directly communicates with the outside environment. Due to the specific anatomical features of the tibia (limited soft tissue coverage), more than quarter of its fractures are classified as open, representing the most common open long-bone injuries. Open tibial fractures frequently cause significant bone comminution, periosteal stripping, soft tissue loss, contamination and are prone to bacterial entry with biofilm formation, which increases the risk of deep bone infection. Objective: The main objective of the study was to determine Prevalence of infection and its associated factors in surgically treated open tibial fracture in Addis Ababa Burn Emergency and Trauma (AaBET) center. Method: A facility based retrospective cross-sectional study was conducted among patient treated for open tibial fracture at AaBET center from September 2018 to September 2021. The data was collected from patient’s chart using structured data collection form, and Data was entered and analyzed using SPSS version 26. Bivariable and multiple binary logistic regression were fitted. Multicollinearity was checked among candidate variables using variance inflation factor and tolerance, which were less than 5 and greater than 0.2, respectively. Model adequacy were tested using Hosmer-Lemeshow goodness of fitness test (P=0.711). AOR at 95% CI was reported, and P-value < 0.05 was considered statistically significant. Result: This study found that 33.9% of the study participants had an infection. Initial IV antibiotic time (AOR=2.924, 95% CI:1.160- 7.370) and time of wound closure from injury (AOR=3.524, 95% CI: 1.798-6.908), injury to admission time (AOR=2.895, 95% CI: 1.402 – 5.977). and definitive fixation method (AOR=0.244, 95% CI: 0.113 – 0.4508) were the factors found to have a statistically significant association with the occurrence of infection. Conclusion: The rate of infection in open tibial fractures indicates that there is a need to improve the management of open tibial fracture treated at AaBET center. Time from injury to admission, time from injury to first debridement, wound closure time, and initial Intra Venous antibiotic time from the injury are an important factor that can be readily amended to improve the infection rate. Whether wound closed before seven days or not were more important factor associated with occurrences of infection.

Keywords: infection, open tibia, fracture, magnitude

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682 Luteolin Exhibits Anti-Diabetic Effects by Increasing Oxidative Capacity and Regulating Anti-Oxidant Metabolism

Authors: Eun-Young Kwon, Myung-Sook Choi, Su-Jung Cho, Ji-Young Choi, So Young Kim, Youngji Han

Abstract:

Overweight and obesity have been linked to a low-grade chronic inflammatory response and an increased risk of developing metabolic syndrome including insulin resistance, type 2 diabetes mellitus and certain types of cancers. Luteolin is a dietary flavonoid with anti-inflammatory, anti-oxidant, anti-cancer and anti-diabetic properties. However, little is known about the detailed mechanism associated with the effect of luteolin on inflammation-related obesity and its complications. The aim of the present study was to reveal the anti-diabetic effect of luteolin in diet-induced obesity mice using “transcriptomics” tool. Thirty-nine male C57BL/6J mice (4-week-old) were randomly divided into 3 groups and were fed normal diet, high-fat diet (HFD, 20% fat) and HFD+0.005% (w/w) luteolin for 16 weeks. Luteolin improved insulin resistance, as measured by HOMA-IR and glucose tolerance, along with preservation action of pancreatic β-cells, compared to the HFD group. Luteoiln was significantly decreased the levels of leptin and ghrelin that play a pivotal role in energy balance, and the macrophage low-grade inflammation marker sCD163 (soluble Cd antigen 163) in plasma. Activities of hepatic anti-oxidant enzymes (catalase and glutathione peroxidase) were increased, while the levels of plasma transaminase (GOT and GPT) and oxidative damage markers (hepatic mitochondria H2O2 and TBARS) were markedly decreased by luteolin supplementation. In addition, luteolin increased oxidative capacity and fatty acid utilization by presenting decrease in enzyme activities of citrate synthase, cytochrome C oxidase and β-hydroxyacyl CoA dehydrogenase and UCP3 gene expression compared to high-fat diet. Moreover, our microarray results of muscle also revealed down-regulated gene expressions associated with TCA cycle by HFD were reversed to normal level by luteolin treatment. Taken together, our results indicate that luteolin is one of bioactive components for improving insulin resistance by increasing oxidative capacity, modulating anti-oxidant metabolism and suppressing inflammatory signaling cascades in diet-induced obese mice. These results provide possible therapeutic targets for prevention and treatment of diet-induced obesity and its complications.

Keywords: anti-oxidant metabolism, diabetes, luteolin, oxidative capacity

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681 Rapid Identification and Diagnosis of the Pathogenic Leptospiras through Comparison among Culture, PCR and Real Time PCR Techniques from Samples of Human and Mouse Feces

Authors: S. Rostampour Yasouri, M. Ghane, M. Doudi

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Leptospirosis is one of the most significant infectious and zoonotic diseases along with global spreading. This disease is causative agent of economoic losses and human fatalities in various countries, including Northern provinces of Iran. The aim of this research is to identify and compare the rapid diagnostic techniques of pathogenic leptospiras, considering the multifacetedness of the disease from a clinical manifestation and premature death of patients. In the spring and summer of 2020-2022, 25 fecal samples were collected from suspected leptospirosis patients and 25 Fecal samples from mice residing in the rice fields and factories in Tonekabon city. Samples were prepared by centrifugation and passing through membrane filters. Culture technique was used in liquid and solid EMJH media during one month of incubation at 30°C. Then, the media were examined microscopically. DNA extraction was conducted by extraction Kit. Diagnosis of leptospiras was enforced by PCR and Real time PCR (SYBR Green) techniques using lipL32 specific primer. Out of the patients, 11 samples (44%) and 8 samples (32%) were determined to be pathogenic Leptospira by Real time PCR and PCR technique, respectively. Out of the mice, 9 Samples (36%) and 3 samples (12%) were determined to be pathogenic Leptospira by the mentioned techniques, respectively. Although the culture technique is considered to be the gold standard technique, but due to the slow growth of pathogenic Leptospira and lack of colony formation of some species, it is not a fast technique. Real time PCR allowed rapid diagnosis with much higher accuracy compared to PCR because PCR could not completely identify samples with lower microbial load.

Keywords: culture, pathogenic leptospiras, PCR, real time PCR

Procedia PDF Downloads 64
680 Analgesic and Anti-inflammatoryactivities of Camel Thorn in Experimental Animals

Authors: Abdelkader H. El Debani, Huda Gargoum, Awad G. Abdellatif

Abstract:

The aim of this study is to investigate analgesic and the anti-inflammatory effects Camel Thorn Extract (CTE) in rodents. Male albino mice weighing 20-25 gm. were divided into different groups each of 8 mice. The control was given normal saline i. p., the first group was given normal saline i. p. the 2nd, 3rd, 4th, groups received different doses of CTE (330, 660, and 1300 mg/kg) respectively and the 6th group received 5mg/kg of morphine i. p. All groups (except the control group) were given acetic acid 40 min after receiving the different treatment. The number of writhes was recorded 5 min after acetic acid injection for 15 min and the % of inhibition of writhing were calculated. Different groups of rats weighing 180- 220 gm., were divided into three groups each of 5 rats. At the beginning, the volumes of the right and left paw in animals were measured by using of the plethysmometer. The 1st group was given 660 mg /kg i. p. of CTE, the 2nd group received indomethacin (5 mg/kg i. p.). One hour later, edema was induced by sub planter injection of 0.1 ml of 1 % freshly prepared suspension of carrageenan into the right hind paws of the rats. The volume of the injected paws and contra-lateral paws were measured at 0, 0.5, 1, 2, 3, 4, and 5 hours using plethysmometer. The volume of the left paw of the rat was subtracted from the volume of the right paw of the same animal. Our results showed that 330,660 and 1300 mg/kg produced 14, 49 and 84%of inhibition of writhes, indicating that CTE has a strong analgesic activity. Our data also showed that the % of inhibition of edema at 30, 60, 120, 180, and 240 min was 14,51,71,61, and 56% in the animals given camel thorn extract whereas these figures in animals given endomethacin were 14, 24, 54, 52, and 54%. These results indicate that camel thorn has anti-inflammatory activities. The mechanism of analgesic and anti-inflammatory activities needs further investigations.

Keywords: camel thorn, imdomethacin, morphine, pharmaceutical medicine

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679 Impact of Treatment of Fragility Fractures Due to Osteoporosis as an Economic Burden Worldwide: A Systematic Review

Authors: Fabiha Tanzeem

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BACKGROUND: Osteoporosis is a skeletal disease that is associated with a reduction in bone mass and microstructures of the bone and deterioration of bone tissue. Fragility fracture due to osteoporosis is the most significant complication of osteoporosis. The increasing prevalence of fragility fractures presents a growing burden on the global economy. There is a rapidly evolving need to improve awareness of the costs associated with these types of fractures and to review current policies and practices for the prevention and management of the disease. This systematic review will identify and describe the direct and indirect costs associated with osteoporotic fragility fractures from a global perspective from the included studies. The review will also find out whether the costs required for the treatment of fragility fractures due to osteoporosis impose an economic burden on the global healthcare system. METHODS: Four major databases were systematically searched for direct and indirect costs of osteoporotic fragility fracture studies in the English Language. PubMed, Cochrane Library, Embase and Google Scholar were searched for suitable articles published between 1990 and July 2020. RESULTS: The original search yielded 1166 papers; from these, 27 articles were selected for this review according to the inclusion and exclusion criteria. In the 27 studies, the highest direct costs were associated with the treatment of pelvic fractures, with the majority of the expenditure due to hospitalization and surgical treatments. It is also observed that most of the articles are from developed countries. CONCLUSION: This review indicates the significance of the economic burden of osteoporosis globally, although more research needs to be done in developing countries. In the treatment of fragility fractures, direct costs were the main reported expenditure in this review. The healthcare costs incurred globally can be significantly reduced by implementing measures to effectively prevent the disease. Raising awareness in children and adults by improving the quality of the information available and standardising policies and planning of services requires further research.

Keywords: systematic review, osteoporosis, cost of illness

Procedia PDF Downloads 151
678 Porous Titanium Scaffolds Fabricated by Metal Injection Moulding Using Potassium-Chloride and Space Holder

Authors: Ali Dehghan Manshadi, David H. StJohn, Matthew S. Dargusch, M. Qian

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Biocompatible, highly porous titanium scaffolds were manufactured by metal injection moulding of spherical titanium powder (powder size: -45 µm) with potassium chloride (powder size: -250 µm) as a space holder. Property evaluation of scaffolds confirmed a high level of compatibility between their mechanical properties and those of human cortical bone. The optimum sintering temperature was found to be 1250°C producing scaffolds with more than 90% interconnected pores in the size range of 200-250 µm, yield stress of 220 MPa and Young’s modulus of 7.80 GPa, all of which are suitable for bone tissue engineering. Increasing the sintering temperature to 1300°C increased the Young’s modulus to 22.0 GPa while reducing the temperature to 1150°C reduced the yield stress to 120 MPa due to incomplete sintering. The residual potassium chloride was determined vs. sintering temperature. A comparison was also made between the porous titanium scaffolds fabricated in this study and the additively manufactured titanium lattices of similar porosity reported in the literature.

Keywords: titanium, metal injection moulding, mechanical properties, scaffolds

Procedia PDF Downloads 189
677 Seal and Heal Miracle Ointment: Effects of Cryopreserved and Lyophilized Amniotic Membrane on Experimentally Induced Diabetic Balb/C Mice

Authors: Elizalde D. Bana

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Healing restores continuity and form through cell replication; hence, conserving structural integrity. In response to the worldwide pressing problem of chronic wounds in the healthcare delivery system, the researcher aims to provide effective intervention to preserve the structural integrity of the person. The wound healing effects of cryopreserved and lyophilized amniotic membrane (AM) of a term fetus embedded into two (2) concentrations (1.5 % and 1.0 %) of absorption-based ointment has been evaluated in vivo using the excision wound healing model 1x1 cm size. The total protein concentration in full term fetus was determined by the Biuret and Bradford methods, which are based on UV-visible spectroscopy. The percentages of protein presence in 9.5 mg (Mass total sample) of Amniotic membrane ranges between 14.77 – 14.46 % in Bradford method, while slightly lower to 13.78 – 13.80 % concentration in Biuret method, respectively. Bradford method evidently showed higher sensitivity for proteins than Biuret test. Overall, the amniotic membrane is composed principally of proteins in which a copious amount of literature substantially proved its healing abilities. After which, an area of 1 cm by 1 cm skin tissue was excised to its full thickness from the dorsolateral aspect of the isogenic mice and was applied twice a day with the ointment formulation having two (2) concentrations for the diabetic group and non-diabetic group. The wounds of each animal were left undressed and its area was measured every other day by a standard measurement formula from day 2,4,6,8,10,12 and 14. By the 14th day, the ointment containing 1.5 % of AM in absorption-based ointment applied to non-diabetic and diabetic group showed 100 % healing. The wound areas in the animals treated with the standard antibiotic, Mupirocin Ointment (Brand X) showed a 100% healing by the 14th day but with traces of scars, indicating that AM prepared from cryopreservation and lyophilization, at that given concentration, had a better wound healing property than the standard antibiotic. Four (4) multivariate tests were used which showed a significant interaction between days and treatments, meaning that the ointments prepared in two differing concentrations and induced in different groups of the mice had a significant effect on the percent of contraction over time. Furthermore, the evaluations of its effectiveness to wound healing were all significant although in differing degrees. It is observed that the higher the concentrations of amniotic membrane, the more effective are the results.

Keywords: wounds, healing, amniotic membrane ointments, biomedical, stem cell

Procedia PDF Downloads 290
676 Cup-Cage Construct for Treatment of Severe Acetabular Bone Loss in Revision Total Hip Arthroplasty: Midterm Clinical and Radiographic Outcomes

Authors: Faran Chaudhry, Anser Daud, Doris Braunstein, Oleg Safir, Allan Gross, Paul Kuzyk

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Background: Acetabular reconstruction in the context of massive acetabular bone loss is challenging. In rare scenarios where the extent of bone loss precludes shell placement (cup-cage), reconstruction at our center consisted of a cage combined with highly porous metal augments. This study evaluates survivorship, complications, and functional outcomes using this technique. Methods: A total of 131 cup-cage implants (129 patients) were included in our retrospective review of revisions of total hip arthroplasty from January 2003 to January 2022. Among these cases, 100/131 (76.3%) were women, the mean age at surgery time was 68.7 years (range, 29.0 to 92.0; SD, 12.4), and the mean follow-up was 7.7 years (range, 0.02 to 20.3; SD, 5.1). Kaplan-Meier survivorship analysis was conducted with failure defined as revision surgery and/or failure of the cup-cage reconstruction. Results: A total of 30 implants (23%) reached the study endpoint involving all-cause revision. Overall survivorship was 74.8% at 10 years and 69.8% at 15 years. Reasons for revision included infection 12/131 (9.1%), dislocation 10/131 (7.6%), aseptic loosening of cup and/or cage 5/131 (3.8%), and aseptic loosening of the femoral stem 2/131 (1.5%). The mean LLD improved from 12.2 ± 15.9 mm to 3.9 ± 11.8 (p<0.05). The horizontal and vertical hip centres on plain film radiographs were significantly improved (p<0.05). Functionally, there was a decrease in the number of patients requiring the use of gait aids, with fewer patients (34, 25.9%) using a cane, walker, or wheelchair post-operatively compared to pre-operatively (58, 44%). There was a significant increase in the number of independent ambulators from 24 to 47 (36%). Conclusion: The cup-cage construct is a reliable treatment option for the treatment of various acetabular defects. There are favourable survivorship, clinical and radiographic outcomes, with a satisfactory complication rate.

Keywords: revision total hip arthroplasty, acetabular defect, pelvic discontinuity, trabecular metal augment, cup-cage

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675 Triple Immunotherapy to Overcome Immune Evasion by Tumors in a Melanoma Mouse Model

Authors: Mary-Ann N. Jallad, Dalal F. Jaber, Alexander M. Abdelnoor

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Introduction: Current evidence confirms that both innate and adaptive immune systems are capable of recognizing and abolishing malignant cells. The emergence of cancerous tumors in patients is, therefore, an indication that certain cancer cells can resist elimination by the immune system through a process known as “immune evasion”. In fact, cancer cells often exploit regulatory mechanisms to escape immunity. Such mechanisms normally exist to control the immune responses and prohibit exaggerated or autoimmune reactions. Recently, immunotherapies have shown promising yet limited results. Therefore this study investigates several immunotherapeutic combinations and devises a triple immunotherapy which harnesses the innate and acquired immune responses towards the annihilation of malignant cells through overcoming their ability of immune evasion, consequently hampering malignant progression and eliminating established tumors. The aims of the study are to rule out acute/chronic toxic effects of the proposed treatment combinations, to assess the effect of these combinations on tumor growth and survival rates, and to investigate potential mechanisms underlying the phenotypic results through analyzing serum levels of anti-tumor cytokines, angiogenic factors and tumor progression indicator, and the tumor-infiltrating immune-cells populations. Methodology: For toxicity analysis, cancer-free C57BL/6 mice are randomized into 9 groups: Group 1 untreated, group 2 treated with sterile saline (solvent of used treatments), group 3 treated with Monophosphoryl-lipid-A, group 4 with anti-CTLA4-antibodies, group 5 with 1-Methyl-Tryptophan (Indolamine-Dioxygenase-1 inhibitor), group 6 with both MPLA and anti-CTLA4-antibodies, group 7 with both MPLA and 1-MT, group 8 with both anti-CTLA4-antibodies and 1-MT, and group 9 with all three: MPLA, anti-CTLA4-antibodies and 1-MT. Mice are monitored throughout the treatment period and for three following months. At that point, histological sections from their main organs are assessed. For tumor progression and survival analysis, a murine melanoma model is generated by injecting analogous mice with B16F10 melanoma cells. These mice are segregated into the listed nine groups. Their tumor size and survival are monitored. For a depiction of underlying mechanisms, melanoma-bearing mice from each group are sacrificed at several time-points. Sera are tested to assess the levels of Interleukin-12 (IL-12), Vascular-Endothelial-Growth Factor (VEGF), and S100B. Furthermore, tumors are excised for analysis of infiltrated immune cell populations including T-cells, macrophages, natural killer cells and immune-regulatory cells. Results: Toxicity analysis shows that all treated groups present no signs of neither acute nor chronic toxicity. Their appearance and weights were comparable to those of control groups throughout the treatment period and for the following 3 months. Moreover, histological sections from their hearts, kidneys, lungs, and livers were normal. Work is ongoing for completion of the remaining study aims. Conclusion: Toxicity was the major concern for the success of the proposed comprehensive combinational therapy. Data generated so far ruled out any acute or chronic toxic effects. Consequently, ongoing work is quite promising and may significantly contribute to the development of more effective immunotherapeutic strategies for the treatment of cancer patients.

Keywords: cancer immunotherapy, check-point blockade, combination therapy, melanoma

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674 Characteristics of Edible Film Made from Skin and Bone Fish Gelatin, Spotted Oceanic Triggerfish (Canthidermis maculata) and Tilapia Fish (Oreochromis niloticus)

Authors: Normalina Arpi, Fahrizal Fahrizal, Dewi Yunita

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Edible films can increase the shelf life of various food products by acting as water, oxygen, and lipid barrier. Fish gelatin as a film-forming agent has unique characteristics but varies depending on fish species. The purpose of this research is to characterize edible film made using skin and bone fish gelatin with the addition of plasticizer. Gelatin of spotted oceanic triggerfish (Canthidermis maculata) and tilapia (Oreochromis niloticus) were used. Glycerol and sorbitol with concentration of 0.25 and 0.5 % were added as a plasticizer. Spotted oceanic triggerfish gelatin with sorbitol resulted film with higher tensile strength and oxygen permeability, whereas tilapia gelatin with glycerol produced an edible film with higher elongation and water vapor permeability. The edible film made of spotted oceanic triggerfish gelatin and 0.25% sorbitol had the best characteristics.

Keywords: edible film, fish gelatin , glycerol, sorbitol

Procedia PDF Downloads 142
673 Interaction Between Gut Microorganisms and Endocrine Disruptors - Effects on Hyperglycaemia

Authors: Karthika Durairaj, Buvaneswari G., Gowdham M., Gilles M., Velmurugan G.

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Background: Hyperglycaemia is the primary cause of metabolic illness. Recently, researchers focused on the possibility that chemical exposure could promote metabolic disease. Hyperglycaemia causes a variety of metabolic diseases dependent on its etiologic conditions. According to animal and population-based research, individual chemical exposure causes health problems through alteration of endocrine function with the influence of microbial influence. We were intrigued by the function of gut microbiota variation in high fat and chemically induced hyperglycaemia. Methodology: C57/Bl6 mice were subjected to two different treatments to generate the etiologic-based diabetes model: I – a high-fat diet with a 45 kcal diet, and II - endocrine disrupting chemicals (EDCs) cocktail. The mice were monitored periodically for changes in body weight and fasting glucose. After 120 days of the experiment, blood anthropometry, faecal metagenomics and metabolomics were performed and analyzed through statistical analysis using one-way ANOVA and student’s t-test. Results: After 120 days of exposure, we found hyperglycaemic changes in both experimental models. The treatment groups also differed in terms of plasma lipid levels, creatinine, and hepatic markers. To determine the influence on glucose metabolism, microbial profiling and metabolite levels were significantly different between groups. The gene expression studies associated with glucose metabolism vary between hosts and their treatments. Conclusion: This research will result in the identification of biomarkers and molecular targets for better diabetes control and treatment.

Keywords: hyperglycaemia, endocrine-disrupting chemicals, gut microbiota, host metabolism

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672 Pre-Implementation of Total Body Irradiation Using Volumetric Modulated Arc Therapy: Full Body Anthropomorphic Phantom Development

Authors: Susana Gonçalves, Joana Lencart, Anabela Gregório Dias

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Introduction: In combination with chemotherapy, Total Body Irradiation (TBI) is most used as part of the conditioning regimen prior to allogeneic hematopoietic stem cell transplantation. Conventional TBI techniques have a long application time but non-conformality of beam-application with the inability to individually spare organs at risk. Our institution’s intention is to start using Volumetric Modulated Arc Therapy (VMAT) techniques to increase homogeneity of delivered radiation. As a first approach, a dosimetric plan was performed on a computed tomography (CT) scan of a Rando Alderson antropomorfic phantom (head and torso), using a set of six arcs distributed along the phantom. However, a full body anthropomorphic phantom is essential to carry out technique validation and implementation. Our aim is to define the physical and chemical characteristics and the ideal manufacturing procedure of upper and lower limbs to our anthropomorphic phantom, for later validate TBI using VMAT. Materials and Methods: To study the better fit between our phantom and limbs, a CT scan of Rando Alderson anthropomorphic phantom was acquired. CT was performed on GE Healthcare equipment (model Optima CT580 W), with slice thickness of 2.5 mm. This CT was also used to access the electronic density of soft tissue and bone through Hounsfield units (HU) analysis. Results: CT images were analyzed and measures were made for the ideal upper and lower limbs. Upper limbs should be build under the following measures: 43cm length and 7cm diameter (next to the shoulder section). Lower limbs should be build under the following measures: 79cm length and 16.5cm diameter (next to the thigh section). As expected, soft tissue and bone have very different electronic density. This is important to choose and analyze different materials to better represent soft tissue and bone characteristics. The approximate HU values of the soft tissue and for bone shall be 35HU and 250HU, respectively. Conclusion: At the moment, several compounds are being developed based on different types of resins and additives in order to be able to control and mimic the various constituent densities of the tissues. Concurrently, several manufacturing techniques are being explored to make it possible to produce the upper and lower limbs in a simple and non-expensive way, in order to finally carry out a systematic and appropriate study of the total body irradiation. This preliminary study was a good starting point to demonstrate the feasibility of TBI with VMAT.

Keywords: TBI, VMAT, anthropomorphic phantom, tissue equivalent materials

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671 An Inquiry on Imaging of Soft Tissues in Micro-Computed Tomography

Authors: Matej Patzelt, Jana Mrzilkova, Jan Dudak, Frantisek Krejci, Jan Zemlicka, Zdenek Wurst, Petr Zach, Vladimir Musil

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Introduction: Micro-CT is well used for examination of bone structures and teeth. On the other hand visualization of the soft tissues is still limited. The goal of our study was to elaborate methodology for soft tissue samples imaging in micro-CT. Methodology: We used organs of rats and mice. We either did a preparation of the organs and fixation in contrast solution or we did cannulation of blood vessels and their injection for imaging of the vascular system. First, we scanned native specimens, then we created corrosive specimens by resins. In the next step, we injected vascular system either by Aurovist contrast agent or by Exitron. In the next step, we focused on soft tissues contrast increase. We scanned samples fixated in Lugol solution, samples fixated in pure ethanol and in formaldehyde solution. All used methods were afterwards compared. Results: Native specimens did not provide sufficient contrast of the tissues in any of organs. Corrosive samples of the blood stream provided great contrast and details; on the other hand, it was necessary to destroy the organ. Further examined possibility was injection of the AuroVist contrast that leads to the great bloodstream contrast. Injection of Exitron contrast agent comparing to Aurovist did not provide such a great contrast. The soft tissues (kidney, heart, lungs, brain, and liver) were best visualized after fixation in ethanol. This type of fixation showed best results in all studied tissues. Lugol solution had great results in muscle tissue. Fixation by formaldehyde solution showed similar quality of contrast in the tissues like ethanol. Conclusion: Before imaging, we need to, first, determinate which structures of the soft tissues we want to visualize. In the case of the bloodstream, the best was AuroVist and corrosive specimens. Muscle tissue is best visualized by Lugol solution. In the case of the organs containing cavities, like kidneys or brain, the best way was ethanol fixation.

Keywords: experimental imaging, fixation, micro-CT, soft tissues

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