Search results for: myocardial tissue engineering

Authors: Sun Il Yu, Jung Hyun Joo, Hwa Sung Shin

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Astrocytes are known as dominant cells in CNS and play a role as a supporter of CNS activity and regeneration. Recently, three-dimensional culture of astrocytes were actively applied to understand in vivo astrocyte works. Electrospun nanofibers are attractive for 3D cell culture system because they have a high surface to volume ratio and porous structure, and have already been used for 3D astrocyte cultures. In this research, the stiffness of cellulose acetate (CA) nanofiber was controlled by heat treatment. As stiffness increased, astrocyte cell viability and adhesion increased. Reactivity of astrocyte was also upregulated in stiffer CA nanofiber in terms of GFAP, an intermediate filament protein. Finally, we demonstrated that stiffness-controllable CA is attractive for astrocyte tissue engineering.

Keywords: astrocyte, cellulose acetate, nanofiber, tissue scaffold

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Authors: Yasuyuki Takahashi, Hayato Ishimura, Masao Miyagawa, Teruhito Mochizuki

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Quantitative measurement of myocardium perfusion is possible with single photon emission computed tomography (SPECT) using a semiconductor detector. However, accumulation of ^99mTc-tetrofosmin in the liver may make it difficult to assess that accurately in the inferior myocardium. Our idea is to reduce the high accumulation in the liver by using dynamic SPECT imaging and a technique called time subtraction. We evaluated the performance of a new SPECT system with a cadmium-zinc-telluride solid-state semi- conductor detector (Discovery NM 530c; GE Healthcare). Our system acquired list-mode raw data over 10 minutes for a typical patient. From the data, ten SPECT images were reconstructed, one for every minute of acquired data. Reconstruction with the semiconductor detector was based on an implementation of a 3-D iterative Bayesian reconstruction algorithm. We studied 20 patients with coronary artery disease (mean age 75.4 ± 12.1 years; range 42-86; 16 males and 4 females). In each subject, 259 MBq of ^99mTc-tetrofosmin was injected intravenously. We performed both a phantom and a clinical study using dynamic SPECT. An approximation to a liver-only image is obtained by reconstructing an image from the early projections during which time the liver accumulation dominates (0.5~2.5 minutes SPECT image-5~10 minutes SPECT image). The extracted liver-only image is then subtracted from a later SPECT image that shows both the liver and the myocardial uptake (5~10 minutes SPECT image-liver-only image). The time subtraction of liver was possible in both a phantom and the clinical study. The visualization of the inferior myocardium was improved. In past reports, higher accumulation in the myocardium due to the overlap of the liver is un-diagnosable. Using our time subtraction method, the image quality of the ^99mTc-tetorofosmin myocardial SPECT image is considerably improved.

Keywords: 99mTc-tetrofosmin, dynamic SPECT, time subtraction, semiconductor detector

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Authors: Hassan Athari, Abdurrahim Bolukbasi, Dogan Ciloglu

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This study represented the respiratory alveoli system, and determined the trajectory of inhaled particles more accurately using the modified three-dimensional model with deformable walls of alveoli. The study also considered the tissue tension in the model to demonstrate the effect of lung. Tissue tensions are transferred by the lung parenchyma and produce the pressure gradient. This load expands the alveoli and establishes a sub-ambient (vacuum) pressure within the lungs. Thus, at the alveolar level, the flow field and movement of alveoli wall lead to an integrated effect. In this research, we assume that the three-dimensional alveolus has a visco-elastic tissue (walls). For accurate investigation of pulmonary tissue mechanical properties on particle transport and alveolar flow field, the actual relevance between tissue movement and airflow is solved by two-way FSI (Fluid Structure Interaction) simulation technique in the alveolus. Therefore, the essence of real simulation of pulmonary breathing mechanics can be achieved by developing a coupled FSI computational model. We, therefore conduct a series of FSI simulations over a range of tissue models and breathing rates. As a result, the fluid flows and streamlines have changed during present flexible model against the rigid models and also the two-way coupling particle trajectories have changed against the one-way particle coupling.

Keywords: FSI, two-way particle coupling, alveoli, CDF

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Authors: Abdou Elhendy

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Numerous study have shown the efficacy of the percutaneous intervention (PCI) and coronary stenting in improving left ventricular function and relieving exertional angina. Furthermore, PCI remains the main line of therapy in acute myocardial infarction. Improvement of procedural techniques and new devices have resulted in an increased number of PCI in those with difficult and extensive lesions, multivessel disease as well as total occlusion. Immediate and late outcome may be compromised by acute thrombosis or the development of fibro-intimal hyperplasia. In addition, progression of coronary artery disease proximal or distal to the stent as well as in non-stented arteries is not uncommon. As a result, complications can occur, such as acute myocardial infarction, worsened heart failure or recurrence of angina. In a stent, restenosis can occur without symptoms or with atypical complaints rendering the clinical diagnosis difficult. Routine invasive angiography is not appropriate as a follow up tool due to associated risk and cost and the limited functional assessment. Exercise and pharmacologic stress testing are increasingly used to evaluate the myocardial function, perfusion and adequacy of revascularization. Information obtained by these techniques provide important clues regarding presence and severity of compromise in myocardial blood flow. Stress echocardiography can be performed in conjunction with exercise or dobutamine infusion. The diagnostic accuracy has been moderate, but the results provide excellent prognostic stratification. Adding myocardial contrast agents can improve imaging quality and allows assessment of both function and perfusion. Stress radionuclide myocardial perfusion imaging is an alternative to evaluate these patients. The extent and severity of wall motion and perfusion abnormalities observed during exercise or pharmacologic stress are predictors of survival and risk of cardiac events. According to current guidelines, stress echocardiography and radionuclide imaging are considered to have appropriate indication among patients after PCI who have cardiac symptoms and those who underwent incomplete revascularization. Stress testing is not recommended in asymptomatic patients, particularly early after revascularization, Coronary CT angiography is increasingly used and provides high sensitive for the diagnosis of coronary artery stenosis. Average sensitivity and specificity for the diagnosis of in stent stenosis in pooled data are 79% and 81%, respectively. Limitations include blooming artifacts and low feasibility in patients with small stents or thick struts. Anatomical and functional cardiac imaging modalities are corner stone for the assessment of patients after PCI and provide salient diagnostic and prognostic information. Current imaging techniques cans serve as gate keeper for coronary angiography, thus limiting the risk of invasive procedures to those who are likely to benefit from subsequent revascularization. The determination of which modality to apply requires careful identification of merits and limitation of each technique as well as the unique characteristic of each individual patient.

Keywords: coronary artery disease, stress testing, cardiac imaging, restenosis

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Authors: Carolina N. França, Jônatas B. do Amaral, Maria C.O. Izar, Ighor L. Teixeira, Francisco A. Fonseca

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Introduction: Atherosclerosis is a progressive disease, characterized by lipid and fibrotic element deposition in large-caliber arteries. Conditions related to the development of atherosclerosis, as dyslipidemia, hypertension, diabetes, and smoking are associated with endothelial dysfunction. There is a frequent recurrence of cardiovascular outcomes after acute myocardial infarction and, at this sense, cycles of mobilization of monocyte subtypes (classical, intermediate and nonclassical) secondary to myocardial infarction may determine the colonization of atherosclerotic plaques in different stages of the development, contributing to early recurrence of ischemic events. The recruitment of different monocyte subsets during inflammatory process requires the expression of chemokine receptors CCR2, CCR5, and CX3CR1, to promote the migration of monocytes to the inflammatory site. The aim of this study was to evaluate the effect of lipid-lowering treatment by six months in the monocyte phenotype and chemokine receptor levels of patients after Acute Myocardial Infarction (AMI). Methods: This is a PROBE (prospective, randomized, open-label trial with blinded endpoints) study (ClinicalTrials.gov Identifier: NCT02428374). Adult patients (n=147) of both genders, ageing 18-75 years, were randomized in a 2x2 factorial design for treatment with rosuvastatin 20 mg/day or simvastatin 40 mg/day plus ezetimibe 10 mg/day as well as ticagrelor 90 mg 2x/day and clopidogrel 75 mg, in addition to conventional AMI therapy. Blood samples were collected at baseline, after one month and six months of treatment. Monocyte subtypes (classical - inflammatory, intermediate - phagocytic and nonclassical – anti-inflammatory) were identified, quantified and characterized by flow cytometry, as well as the expressions of the chemokine receptors (CCR2, CCR5 and CX3CR1) were also evaluated in the mononuclear cells. Results: After six months of treatment, there was an increase in the percentage of classical monocytes and reduction in the nonclassical monocytes (p=0.038 and p < 0.0001 Friedman Test), without differences for intermediate monocytes. Besides, classical monocytes had higher expressions of CCR5 and CX3CR1 after treatment, without differences related to CCR2 (p < 0.0001 for CCR5 and CX3CR1; p=0.175 for CCR2). Intermediate monocytes had higher expressions of CCR5 and CX3CR1 and lower expression of CCR2 (p = 0.003; p < 0.0001 and p = 0.011, respectively). Nonclassical monocytes had lower expressions of CCR2 and CCR5, without differences for CX3CR1 (p < 0.0001; p = 0.009 and p = 0.138, respectively). There were no differences after the comparison between the four treatment arms. Conclusion: The data suggest a time-dependent modulation of classical and nonclassical monocytes and chemokine receptor levels. The higher percentage of classical monocytes (inflammatory cells) suggest a residual inflammatory risk, even under preconized treatments to AMI. Indeed, these changes do not seem to be affected by choice of the lipid-lowering strategy.

Keywords: acute myocardial infarction, chemokine receptors, lipid-lowering treatment, monocyte subtypes

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Authors: Ximena Calle, Plinio Cantero-López, Felipe Muñoz-Córdova, Mayarling-Francisca Troncoso, Sergio Lavandero, Valentina Parra

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MUL1, a mitochondrial E3 ubiquitin ligase anchored to the outer mitochondrial membrane, is highly expressed in the heart. MUL1 is involved in multiple biological pathways associated with mitochondrial dynamics. Increased MUL1 affects the balance between fission and fusion, affecting mitochondrial function, which plays a crucial role in myocardial function. Therefore, it is interesting to evaluate the effect of cardiac-specific overexpression of MUL1 on myocardial function. Aim: To determine heart functionality in a mouse model with cardio-specific overexpression MUL1 protein. Methods and Results: Male C57BL/Tg transgenic mice with cardiomyocyte-specific overexpression of MUL1 (n=10) and control (n=4) were evaluated at 12, 27, and 35 weeks of age. Glucose tolerance curve determination was performed after a 6-hours fast to assess metabolic capacity, treadmill test, and systolic, and diastolic pressure was evaluated by the mouse tail-cuff blood pressure system equipment. The result showed no glucose tolerance curve, and the treadmill test demonstrated no significant changes between groups. However, substantial changes in diastolic function were observed by ultrasound and determination of cardiac hypertrophy proteins by western blot. Conclusions: Cardio-specific overexpression of MUL1 in mice without any treatment affects diastolic cardiac function, thus showing the important role contributed by MUL1 in the heart. Future research should evaluate the effect of cardiomyocyte-specific overexpression of MUL1 in pathological conditions such as a high-fat diet is one of the main risk factors for cardiovascular disease.

Keywords: diastolic dysfunction, hypertrophy cardiac, mitochondrial E3 ubiquitin ligase 1, MUL1

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Authors: Yusser Olguín, Diego Benavente, Fernando Dorta, Nicole Orellana, Cristian Acevedo

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One of the greatest challenges of tissue engineering is the generation of materials in which the highest possible number of conditions can be incorporated to stimulate the proliferation and differentiation of cells, which will be transformed together with the material into new functional tissue. In this sense, considering the properties of microfluidics and its relationship with cellular micro-environments, the possibility of controlling flow patterns and the ability to design diverse patterns in the chips, a microfluidic cell culture system can be established as a means for the evaluation of the effect of different parameters in a controlled and precise manner. Specifically in relation to the study and development of alternatives in peripheral nervous tissue engineering, it is necessary to consider different physical and chemical neurotrophic stimuli that promote cell growth and differentiation. Chemical stimuli include certain vitamins, glucocorticoids, gangliosides, and growth factors, while physical stimuli include topological stimuli, mechanical forces of the cellular environment and electrical stimulation. In this context, the present investigation shows the results of cell stimulation in a microbioreactor using electrical and chemical stimuli, where the differentiation of PC12 cells as a neuronal model is evidenced by neurite expression, dependent on the stimuli and their combination. The results were analysed with a multi-factor statistical approach, showing several relationships and dependencies between different parameters. Chip design, operating parameters and concentrations of neurotrophic chemical factors were found to be preponderant, based on the characteristics of the electrical stimuli.

Keywords: microfluidics, nerve tissue engineering, microbioreactor, electrical stimuli

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Authors: Ali Kassem, Yhea Kishik, Ali Hassan, Mohamed Abdelwahab

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Introduction: Accelerated coronary and peripheral vascular atherosclerosis is one of the most common and chronic complications of diabetes mellitus. A recent aspect of coronary artery disease in this condition is its silent nature. The aim of the work: Detection of the prevalence of silent myocardial ischemia (SMI) in Upper Egypt type 2 diabetic males and to select male diabetic population who should be screened for SMI. Patients and methods: 100 type 2 diabetic male patients with a negative history of angina or anginal equivalent symptoms and 30 healthy control were included. Full medical history and thorough clinical examination were done for all participants. Fasting and post prandial blood glucose level, lipid profile, (HbA1c), microalbuminuria, and C-reactive protein were done for all participants Resting ECG, trans-thoracic echocardiography, treadmill exercise ECG, myocardial perfusion imaging were done for all participants and patients positive for one or more NITs were subjected for coronary angiography. Results Twenty nine patients (29%) were positive for one or more NITs in the patients group compared to only one case (3.3%) in the controls. After coronary angiography, 20 patients were positive for significant coronary artery stenosis in the patients group, while it was refused to be done by the patient in the controls. There were statistical significant difference between the two groups regarding, hypertension, dyslipidemia and obesity, family history of DM and IHD with higher levels of microalbuminuria, C-reactive protein, total lipids in patient group versus controls According to coronary angiography, patients were subdivided into two subgroups, 20 positive for SMI (positive for coronary angiography) and 80 negative for SMI (negative for coronary angiography). No statistical difference regarding family history of DM and type of diabetic therapy was found between the two subgroups. Yet, smoking, hypertension, obesity, dyslipidemia and family history of IHD were significantly higher in diabetics positive versus those negative for SMI. 90% of patients in subgroup positive for SMI had two or more cardiac risk factors while only two patients had one cardiac risk factor (10%). Uncontrolled DM was detected more in patients positive for SMI. Diabetic complications were more prevalent in patients positive for SMI versus those negative for SMI. Most of the patients positive for SMI have DM more than 5 years duration. Resting ECG and resting Echo detected only 6 and 11 cases, respectively, of the 20 positive cases in group positive for SMI compared to treadmill exercise ECG and myocardial perfusion imaging that detected 16 and 18 cases respectively, Conclusion: Type 2 diabetic male patients should be screened for detection of SMI when aged above 50 years old, diabetes duration is more than 5 years, presence of two or more cardiac risk factors and/or patients suffering from one or more of the chronic diabetic complications. CRP, is an important parameter for selection of type 2 diabetic male patients who should be screened for SMI. Non invasive cardiac tests are reliable for screening of SMI in these patients in our locality.

Keywords: C-reactive protein, Silent myocardial ischemia, Stress tests, type 2 DM

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Authors: G. Dadashova, A. Bakhshaliyev

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Aim: Determine gender differences in the etiology and clinical outcomes, as well as in the remodeling of the left ventricle (LV) in patients with chronic heart failure (CHF), suffering from arterial hypertension (AH) and coronary heart disease (CHD). Material and methods: The study included 112 patients of both sexes; aged 45 to 60 years with postinfarction cardiosclerosis had functional class (FC) heart failure II-IV of NYHA which were examined on the basis of Azerbaijan Scientific Research Institute of Cardiology. The patients were divided into 2 groups: 1st c. 60 males, mean age 54,8 ± 3,3 years, and 2nd gr 52 women, mean age 55,8 ± 3,1 years. To assess cardiac hemodynamic all patients underwent echocardiography (B-M-modes) using ‘Vivid 3’. Thus on the basis of indicators such as the index of the relative thickness of the left ventricle wall and the index of left ventricular mass (LVMI) was identified the architectonic model of the left ventricle. Results: According to our research leading cause of heart failure in women is 50.5% of cases of hypertension, ischemic heart disease 23.7% (with 79.5% of the cases developed in patients with chronic heart failure who did not have a history of myocardial infarction). While in men is the undisputed leader of CHD, forming 78.3% of CHF (80.3% in men with CHF occurred after myocardial infarction). According to our research in women more often than men CHF develops a type of diastolic dysfunction (DD, and left ventricular ejection fraction remained unchanged. Since DD occurs in men at 65,8% vs. 76,4% of women when p < 0,05. In the group of women was more common prognostic neblagopryatnye remodeling - eccentric hypertrophy of the left ventricle: 68% vs. 54.5% among men (p < 0,05), concentric left ventricular hypertrophy: 21% in women vs 19,1% (p > 0,05 ). Conclusions: Patients with heart failure are a number of gender-specific: the prevalence of hypertension in women, and coronary heart disease in men. While in women with heart failure often recorded diastolic dysfunction and characterized by the development of prognostically unfavorable remodeling types: eccentric and concentric LV hypertrophy.

Keywords: chronic heart failure, arterial hypertension, remodeling, diastolic dysfunction, men, women, ischemic heart disease

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Authors: A. Beatti, L. Chipchase, A. Rayner, T. Souvlis

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The aims of this study were to investigate the depth of interferential current (IFC) penetration through soft tissue and to investigate the area over which IFC spreads during clinical application. Premodulated IFC and ‘true’ IFC at beat frequencies of 4, 40 and 90Hz were applied via four electrodes to the distal medial thigh of 15 healthy subjects. The current was measured via three Teflon coated fine needle electrodes that were inserted into the superficial layer of skin, then into the subcutaneous tissue (≈1 cm deep) and then into muscle tissue (≈2 cm deep). The needle electrodes were placed in the middle of the four IFC electrodes, between two channels and outside the four electrodes. Readings were taken at each tissue depth from each electrode during each treatment frequency then digitized and stored for analysis. All voltages were greater at all depths and locations than baseline (p < 0.01) and voltages decreased with depth (P=0.039). Lower voltages of all currents were recorded in the middle of the four electrodes with the highest voltage being recorded outside the four electrodes in all depths (P=0.000).For each frequency of ‘true’ IFC, the voltage was higher in the superficial layer outside the electrodes (P ≤ 0.01).Premodulated had higher voltages along the line of one circuit (P ≤ 0.01). Clinically, IFC appears to pass through skin layers to depth and is more efficient than premodulated IFC when targeting muscle tissue.

Keywords: electrotherapy, interferential current, interferential therapy, medium frequency current

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Authors: Ashraf Ali, Kriti Upadhyay, Puja Sohal, Anant Mohan, Randeep Guleria

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Background: Gene silencing by aberrant promoter hypermethylation is common in lung cancer and is an initiating event in its development. Aim: To evaluate the gene promoter hypermethylation frequency in serum and tissue of lung cancer patients. Method: 95 newly diagnosed untreated advance stage lung cancer patients and 50 cancer free matched controls were studied. Bisulfite modification of tissue and serum DNA was done; modified DNA was used as a template for methylation-specific PCR analysis. Survival was assessed for one year. Results: Of 95 patients, 82% were non-small cell lung cancer (34% squamous cell carcinoma, 34% non-small cell lung cancer and 14% adenocarcinoma) and 18% were small cell lung cancer. Biopsy revealed that tissue of 89% and 75% of lung cancer patients and 85% and 52% of controls had promoter hypermethylated for MGMT (p=0.35) and p16(p<0.001) gene, respectively. In serum, 33% and 49% of lung cancer patients and 28% and 43% controls were positive for MGMT and p16 gene. No significant correlation was found between survival and clinico-pathological parameters. Conclusion: High gene promoter methylation frequency of p16 gene in tissue biopsy may be linked with early stages of carcinogenesis. Appropriate follow-up is required for confirmation of this finding.

Keywords: lung cancer, MS- PCR, methylation, molecular biology

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Authors: M. Alam, P. Seshaiyer

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The rupture predictability of intracranial aneurysm is one of the most important parameters for physicians in surgical treatment. As most of the intracranial aneurysms are asymptomatic, still the rupture potential of both symptomatic and asymptomatic lesions is relatively unknown. Moreover, an intracranial aneurysm constrained by a nerve tissue might be a common scenario for a physician to deal with during the treatment process. Here, we perform a computational modeling of nerve tissue constrained intracranial saccular aneurysm to show a protective role of constrained tissue on the aneurysm. A comparative parametric study of the model also performs taking long constraint, medium constraint, short constraint, point contact, narrow neck aneurysm, wide neck aneurysm as parameters for the analysis. Results show that contact constraint aneurysm generates less stress near the fundus compared to no constraint aneurysm, hence works as a protective wall for the aneurysm not to be ruptured.

Keywords: rupture potential, intracranial saccular aneurysm, anisotropic hyper-elastic material, finite element analysis

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Authors: A. M. Malagon Escandon, J. A. Arenas Alatorre, C. P. Chaires Rosas, N. A. Vazquez Torres, B. Hernandez Tellez, G. Pinon Zarate, M. Herrera Enriquez, A. E. Castell Rodriguez

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The current approach to the treatment of bone defects involves the use of scaffolds that provide a biological and mechanically stable niche to favor tissue repair. Despite the significant progress in the field of bone tissue engineering, several main problems associated are attributed to giving a low biodegradation degree, does not promote osseointegration and regeneration, if the bone is not healing as well as expected or fails to heal, will not be given a proper ossification or new bone formation. The actual approaches of bone tissue regeneration are directed to the use of decellularized native extracellular matrices, which are able of retain their own architecture, mechanic properties, biodegradability and promote new bone formation because they are capable of conserving proteins and other factors that are founded in physiological concentrations. Therefore, we propose an extracellular matrix-based bioscaffolds derived from bovine cancellous bone, which is processed by decellularization, demineralization, and hydrolysis of the collagen protein, these protocols have been successfully carried out in other organs and tissues; the effectiveness of its biosafety has also been previously evaluated in vivo and Food and Drug Administration (FDA) approved. In the specific case of bone, a more complex treatment is needed in comparison with other organs and tissues because is necessary demineralization and collagen denaturalization. The present work was made in order to obtain a temporal scaffold that succeed in degradation in an inversely proportional way to the synthesis of extracellular matrix and the maturation of the bone by the cells of the host.

Keywords: bioactive, biodegradable, bone, extracellular matrix-based bioscaffolds, stem cells, tissue engineering

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Authors: Parthasarathi Pramanik

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Body packing is a way of transfer drugs across the international border or any drug prohibited area. The drugs are usually hidden in body packets inside the anatomical body cavities like mouth, intestines, rectum, ear, vagina etc. Cocaine is a very common drug for body packing across the world. A 48 year old male was reported dead in his hotel after complaining of chest pain and vomiting. At autopsy, there were eighty-two white cylindrical body packs in the stomach, small and large intestines. Seals of few of the packets were opened. Toxicological examination revealed presence of cocaine in the stomach, liver, kidney and hair samples. Microscopically, presence of myocardial necrosis with interstitial oedema along with hypertrophy and fibrosis of the myocardial fibre suggested heart failure due to cocaine cardio toxicity. However, focal lymphocyte infiltration and perivascular fibrosis in the myocardium also indicated chronic cocaine toxicity of the deceased. After careful autopsy examination it was considered the victim was died due congestive heart failure secondary to acute and chronic cocaine poisoning.

Keywords: cardiac failure, cocaine, body packer, sudden death

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Authors: Lin Feng, E. Lingling, Hongchen Liu

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In order to evaluate the effects of autologous blood vessels and nerves on vascularization. A dog model of tissue-engineered bone vascularization was established by constructing inferior alveolar neurovascular bundles through the mandibular canal. Sixteen 12-month-old healthy beagles were randomly divided into two groups (n=8). Group A retained inferior alveolar neurovascular bundles, and Group B retained inferior alveolar nerves. Bone marrow mesenchymal stem cells were injected into β-tricalcium phosphate to prepare internal tissue-engineered bone scaffold. A personalized titanium mesh was then prepared by rapid prototyping and fixed by external titanium scaffold. Two dogs in each group were sacrificed on the 30th, 45th, 60th, and 90th postoperative days respectively. The bone was visually examined, scanned by CT, and subjected to HE staining, immunohistochemical staining, vascular casting and PCR to detect the changes in osteogenesis and vascularization.The two groups had similar outcomes in regard to osteogenesis and vascularization (P>0.05) both showed remarkable regenerative capacities. The model of tissue-engineered bone vascularization is potentially applicable in clinical practice to allow satisfactory osteogenesis and vascularization.

Keywords: inferior alveolar neurovascular bundle, osteogenesis, tissue-engineered bone, vascularization

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Authors: Souradip Paul, Arijit Paramanick, M. Suheshkumar Singh

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Traumatic injury is the leading worldwide health problem. Annually, millions of surgical wounds are created for the sake of routine medical care. The healing of these unintended injuries is always monitored based on visual inspection. The maximal restoration of tissue functionality remains a significant concern of clinical care. Although minor injuries heal well with proper care and medical treatment, large injuries negatively influence various factors (vasculature insufficiency, tissue coagulation) and cause poor healing. Demographically, the number of people suffering from severe wounds and impaired healing conditions is burdensome for both human health and the economy. An incomplete understanding of the functional and molecular mechanism of tissue healing often leads to a lack of proper therapies and treatment. Hence, strong and promising medical guidance is necessary for monitoring the tissue regeneration processes. Photoacoustic imaging (PAI), is a non-invasive, hybrid imaging modality that can provide a suitable solution in this regard. Light combined with sound offers structural, functional and molecular information from the higher penetration depth. Therefore, molecular and structural mechanisms of tissue repair will be readily observable in PAI from the superficial layer and in the deep tissue region. Blood vessel formation and its growth is an essential tissue-repairing components. These vessels supply nutrition and oxygen to the cell in the wound region. Angiogenesis (formation of new capillaries from existing blood vessels) contributes to new blood vessel formation during tissue repair. The betterment of tissue healing directly depends on angiogenesis. Other optical microscopy techniques can visualize angiogenesis in micron-scale penetration depth but are unable to provide deep tissue information. PAI overcomes this barrier due to its unique capability. It is ideally suited for deep tissue imaging and provides the rich optical contrast generated by hemoglobin in blood vessels. Hence, an early angiogenesis detection method provided by PAI leads to monitoring the medical treatment of the wound. Along with functional property, mechanical property also plays a key role in tissue regeneration. The wound heals through a dynamic series of physiological events like coagulation, granulation tissue formation, and extracellular matrix (ECM) remodeling. Therefore tissue elasticity changes, can be identified using non-contact photoacoustic elastography (PAE). In a nutshell, angiogenesis and biomechanical properties are both critical parameters for tissue healing and these can be characterized in a single imaging modality (PAI).

Keywords: PAT, wound healing, tissue coagulation, angiogenesis

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Authors: S. M. Satyam, K. L. Bairy, R. Pirasanthan, R. L. Vaishnav

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Zincovit tablets have been used as nutritional food supplement over a prolonged period of time. The aim of the present study was to investigate the cardio-protective effect of combined formulation of grape seed extract and Zincovit tablets (40, 80 and 160 mg/kg) using a Langendorff model of ischemia-reperfusion in Wistar rats. Following 21 days of pre-treatment, combined formulation of grape seed extract and Zincovit tablets significantly attenuated ischemia-reperfusion induced cardiac injury in terms of increased coronary flow rate (p < 0.01), decreased creatine kinase activity in coronary effluent (p < 0.05), decreased MDA (p < 0.001), 4-HNE (p < 0.001) and increased protein thiol content (p < 0.01) in comparison with the untreated (control) group. This study opens an avenue to clinical studies to demonstrate the validity of this paradigm as a nutritional food supplement, which could improve the clinical outcome of patients subjected to percutaneous angioplasty.

Keywords: grape seed extract, myocardial ischemia-reperfusion injury, oxidative stress, Zincovit tablets

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Authors: Mohammad Shakir, Reshma Jolly, Mohammad Shoeb Khan, Noor-E-Iram

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A nanocomposite system incorporating dextrin into nano-hydroxyapatite/chitin matrix (n-HA/DX/CT) has been successfully synthesized via co-precipitation route at room temperature for the application in bone tissue engineering by investigating biocompatibility, cytotoxicity and mechanical properties. The FTIR spectra of n-HA/DX/CT nanocomposite indicated a considerable intermolecular interaction between the various components of the system. The results of XRD, TEM and TGA/DTA revealed that the crystallinity, size and thermal stability of the n-HA/DX/CT scaffold has decreased and increased respectively. The result of SEM image of the n-HA/DX/CT scaffold indicated that the incorporation of dextrin affected the surface morphology while considerable in-vitro bioactivity has been observed in n-HA/DX/CT based on SBF study, referring a step towards possibility of making direct bond to living bone if implanted. Moreover, MTT assay suggested the non-toxic nature of n-HA/DX/CT to murine fibroblast L929 cells. The swelling study of n-HA/DX/CT scaffold indicated the low swelling rate for n-HADX/CT. All these results have paved the way for n-HA/DX/CT to be used as a competent material for bone tissue engineering.

Keywords: autograft, chitin, dextrin, nanocomposite

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Authors: Azadeh Rouhandeh, Chris Joslin, Zhen Qu, Yuu Ono

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The centre of rotation of the hip joint is needed for an accurate simulation of the joint performance in many applications such as pre-operative planning simulation, human gait analysis, and hip joint disorders. In human movement analysis, the hip joint center can be estimated using a functional method based on the relative motion of the femur to pelvis measured using reflective markers attached to the skin surface. The principal source of errors in estimation of hip joint centre location using functional methods is soft tissue artefacts due to the relative motion between the markers and bone. One of the main objectives in human movement analysis is the assessment of soft tissue artefact as the accuracy of functional methods depends upon it. Various studies have described the movement of soft tissue artefact invasively, such as intra-cortical pins, external fixators, percutaneous skeletal trackers, and Roentgen photogrammetry. The goal of this study is to present a non-invasive method to assess the displacements of the markers relative to the underlying bone using optical motion capture data and tissue thickness from ultrasound measurements during flexion, extension, and abduction (all with knee extended) of the hip joint. Results show that the artefact skin marker displacements are non-linear and larger in areas closer to the hip joint. Also marker displacements are dependent on the movement type and relatively larger in abduction movement. The quantification of soft tissue artefacts can be used as a basis for a correction procedure for hip joint kinematics.

Keywords: hip joint center, motion capture, soft tissue artefact, ultrasound depth measurement

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Authors: Sayyed-javad Ziaolhagh, Ali-Reza Saadatifar

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Introduction: Athletes frequently perform anabolic steroid resistance exercise, but the effects of medical doses and abuse along with resistance exercise on structural damage to the Pancreases and also jujube extract are unknown. The aim of this study was to investigate the effects of resistance training on body weight and hip fractures induced by boldenone injection in male rats. Materials and methods: In this experimental study, 30 male Wistar rats aged 8-12 weeks (weight 202±9.34 g) were randomly divided into five groups: control, boldenone, extract of iujuba+boldenone, boldenone+resistance training and boldenone+resistance training +extract of jujuba. The resistance training program included climbing the ladder for 8 weeks, 3 days a week, 1 session training in a day and each session consisted of the 3 sets and 5 repetitions. Injection was conducted in depth in the hamstring once a week on an appointed day. After anesthesia, autopsy was performed, and the cardiac tissue was isolated. Results: Results showed that boldenone caused tissue damage, congestion, and nuclei unclear and diffuse. In the group "resistance + Boldenone," The Pancreases tissue showed a high degree of hyperemia, and the muscle cells were somewhat abnormal. In boldenone + jujube, the appearance of the tissue was normal, and the rejuvenating effect was visible. Conclusion: Boldenone appears to cause structural damage to the Pancreases tissue. Strength training with Jujube Extract can reduce part of the pancreatic system disorders (necrosis and inflammation) caused by anabolic steroid use.

Keywords: boldenone, Jujube extract, pancreases tissue, resistance training

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Authors: Hassan Mohammadi Khujin

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Tissue engineering is the science of tissues and complex organs creation using scaffolds, cells and biologically active components. Most cells require scaffolds to grow and proliferate. These temporary support structures for tissue regeneration are later replaced with extracellular matrix produced inside the body. Recent advances in additive manufacturing methods allow production of highly porous, complex three dimensional scaffolds suitable for cell growth and proliferation. The current paper investigates the mechanical properties, including elastic modulus and compressive strength, as well as fluid flow dynamics, including permeability and flow-induced shear stress of scaffolds with four triply periodic minimal surface (TPMS) configurations, namely the Schwarz primitive, the Schwarz diamond, the gyroid, and the Neovius structures. Higher porosity in all scaffold types resulted in lower mechanical properties. The permeability of the scaffolds was determined using Darcy's law with reference to geometrical parameters and the pressure drop derived from the computational fluid dynamics (CFD) analysis. Higher porosity enhanced permeability and reduced wall shear stress in all scaffold designs.

Keywords: highly porous scaffolds, tissue engineering, finite elements analysis, CFD analysis

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Authors: Yusra Pintaningrum, Ilma Fahira Basyir, Sony Hilal Wicaksono, Vito A. Damay

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Background: Coronary artery calcium (CAC) scores play an important role in improving prognostic accuracy and can be selectively used to guide the allocation of statin therapy for atherosclerotic cardiovascular disease outcomes and potentially associated with the occurrence of MACE (Major Adverse Cardiovascular Event) and MI (Myocardial Infarction). Objective: This systematic review and meta-analysis aim to analyze the findings of a study about CAC Score and statin treatment effect on MI and MACE risk. Methods: Search for published scientific articles using the PRISMA (Preferred Reporting, Items for Systematic Reviews and Meta-Analysis) method conducted on PubMed, Cochrane Library, and Medline databases published in the last 20 years on “coronary artery calcium” AND “statin” AND “cardiovascular disease” Further systematic review and meta-analysis using RevMan version 5.4 were performed based on the included published scientific articles. Results: Based on 11 studies included with a total of 1055 participants, we performed a meta-analysis and found that individuals with CAC score > 0 increased risk ratio of MI 8.48 (RR = 9.48: 95% CI: 6.22 – 14.45) times and MACE 2.48 (RR = 3.48: 95% CI: 2.98 – 4.05) times higher than CAC score 0 individual. Statin compared against non-statin treatment showed a statistically insignificant overall effect on the risk of MI (P = 0.81) and MACE (P = 0.89) in an individual with elevated CAC score 1 – 100 (P = 0.65) and > 100 (P = 0.11). Conclusions: This study found that an elevated CAC scores individual has a higher risk of MI and MACE than a non-elevated CAC score individual. There is no significant effect of statin compared against non-statin treatment to reduce MI and MACE in elevated CAC score individuals of 1 – 100 or > 100.

Keywords: coronary artery calcium, statin, cardiovascular disease, myocardial infarction, MACE

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Authors: Mehrdad Sheikhvatan, Mohammad Ali Boroumand, Mehrdad Behmanesh, Shayan Ziaee

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Contradictory results have been obtained regarding the role of integrin, beta 3 (ITGB3) gene polymorphisms in occurrence of acute myocardial infarction (MI) in patients with coronary artery disease (CAD). Hence, we aimed to assess the association between 1565C/T polymorphism of ITGB3 gene and increased risk for acute MI in patients who suffered premature CAD in Iranian population. Our prospective study included 1000 patients (492 men and 508 women aged 21 to 55 years) referred to Tehran Heart center during a period of four years from 2008 to 2011 with the final diagnosis of premature CAD and classified into two groups with history of MI (n = 461) and without of MI (n = 539). The polymorphism variants were determined by PCR-RFLP technique by entering 10% of randomized samples and then genotyping of the polymorphism was also conducted by High Resolution Melting (HRM) method. Among study samples, 640 were followed with a median follow-up time 45.74 months for determining association of long-term major adverse cardiac events (MACE) and genotypes of polymorphisms. There was no significant difference in the frequency of 1565C/T polymorphism between the MI and non-MI groups. The frequency of wild genotype was 69.2% and 72.2%, the frequency of homozygous genotype was 21.3% and 18.4%, and the frequency of mutant genotype was 9.5% and 9.5%, respectively (p=0.505). Results were also similar when adjusted for covariates in a multivariate logistic regression model. No significant difference was also found in total-MACE free survival rate between the patients with different genotypes of 1565C/T polymorphism in both MI and non-MI group. The carriage of the 1565C/T polymorphism of ITGB3 gene seems unlikely to be a significant risk factor for the development of MI in Iranian patients with premature CAD. The presence of this ITGB3 gene polymorphism may not also predict long-term cardiac events.

Keywords: coronary artery disease, myocardial infarction, gene, integrin, beta 3, polymorphism

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Authors: P. I. Bobyleva, E. R. Andreeva, I. V. Andrianova, E. V. Maslova, L. B. Buravkova

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This work studied the ability of adipose tissue-derived mesenchymal stromal cells (MSCs) to form stroma for expansion of cord blood hematopoietic cells. We showed that 72-hour interaction of MSCs with cord blood mononuclear cells (MNCs) in vitro at atmospheric (20%) and low (5%) O2 conditions increased the expression of ICAM-1, HCAM (at the beginning of interaction) on MSCs. Viability of MSCs and MNCs were maintained at high level. Adhesion of MNCs to MSCs was faster at 20% O2. MSCs promoted the proliferation of adhered MNCs to form the suspension containing great number of hematopoietic colony-forming units, and this effect was more pronounced at 5% O2. Thus, adipose-derived MSCs supplied sufficient stromal support to cord blood MNCs both at 20% and 5% О2, providing their adhesion with further expansion of new generation of different hematopoietic lineages.

Keywords: hematopoietic stem and progenitor cells, mesenchymal stromal cells, tissue-related oxygen, adipose tissue

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Authors: Simone F. Medeiros, Isabela F. Santos, Rodolfo M. Moraes, Jaspreet K. Kular, Marcus A. Johns, Ram Sharma, Amilton M. Santos

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Tissue engineering aims to develop alternatives to treat damaged tissues by promoting their regeneration. Its basic principle is to place cells on a scaffold capable of promoting cell functions, and for this purpose, polymeric nanoparticles have been successfully used due to the ability of some macro chains to mimic the extracellular matrix and influence cell functions. In general, nanoparticles require surface chemical modification to achieve cell adhesion, and recent advances in their synthesis include methods for modifying the ligand density and distribution onto nanoparticles surface. However, this work reports the development of biodegradable polymeric nanoparticles capable of promoting cellular adhesion without any surface chemical modification by ligands. Biocompatible and biodegradable nanoparticles based on poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBHV) were synthesized by solvent evaporation method. The produced nanoparticles were small in size (85 and 125 nm) and colloidally stable against time in aqueous solution. Morphology evaluation showed their spherical shape with small polydispersity. Human osteoblast-like cells (MG63) were cultured in the presence of PHBHV nanoparticles, and growth kinetics were compared to those grown on tissue culture polystyrene (TCPS). Cell attachment on non-tissue culture polystyrene (non-TCPS) pre-coated with nanoparticles was assessed and compared to attachment on TCPS. These findings reveal the potential of PHBHV nanoparticles for cell adhesion and growth, without requiring a matrix ligand to support cells, to be used as scaffolds, in tissue engineering applications.

Keywords: tissue engineering, PHBHV, stem cells, cellular attachment

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Authors: Barsha Saha, Shouvik Chakravarty, Sukanta Ray, Kshaunish Das, Nidhan K. Biswas, Srikanta Goswami

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Pancreatic Ductal Adenocarcinoma is a well-recognised cause of cancer death with a five-year survival rate of about 9%, and its incidence in India has been found to be increased manifold in recent years. Due to delayed detection, this highly metastatic disease has a poor prognosis. Several molecular alterations happen during the progression of the disease from pre-cancerous conditions, and many such alterations could be investigated for their biomarker potential. MicroRNAs have been shown to be prognostic for PDAC patients in a variety of studies. We hereby used NGS technologies to evaluate the role of small RNA changes during pancreatic cancer development from chronic pancreatitis. Plasma samples were collected from pancreatic cancer patients (n=16), chronic pancreatitis patients (n=8), and also from normal individuals (n=16). Pancreatic tumour tissue (n=5) and adjacent normal tissue samples (n=5) were also collected. Sequencing of small RNAs was carried out after small RNAs were isolated from plasma samples and tissue samples. We find that certain microRNAs are highly deregulated in pancreatic cancer patients in comparison to normal samples. A combinatorial analysis of plasma and tissue microRNAs and subsequent exploration of their targets and altered molecular pathways could not only identify potential biomarkers for disease diagnosis but also help to understand the underlying mechanism.

Keywords: small RNA sequencing, pancreatic cancer, biomarkers, tissue sample

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Authors: Sheng Yu Chen, Shi-Heng Wang

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Aim: Based on human, animal experiments, and genetic studies, cysteinyl leukotrienes, LTC4, LTD4, and LTE4, are inflammatory substances that are metabolized by 5-lipooxygenase from arachidonic acid, and these substances trigger asthma. In addition, the synthetic pathway of cysteinyl leukotriene is relevant to the increase in cardiovascular diseases such as myocardial ischemia and stroke. Given the situation, we aim to investigate whether cysteinyl leukotrienes receptor antagonist (LTRA), montelukast which cures those who have asthma has potential protective effects on cardiovascular diseases. Method: We conducted a cohort study, and enrolled participants which are newly diagnosed with asthma (ICD-9 CM code 493. X) between 2002 to 2011. The data source is from Taiwan National Health Insurance Research Database Patients with a previous history of myocardial infarction or ischemic stroke were excluded. Among the remaining participants, every montelukast user was matched with two randomly non-users by sex, and age. The incident cardiovascular diseases, including myocardial infarction and ischemic stroke, were regarded as outcomes. We followed the participants until outcomes come first or the end of the following period. To explore the protective effect of montelukast on the risk of cardiovascular disease, we use multivariable Cox regression to estimate the hazard ratio with adjustment for potential confounding factors. Result: There are 55876 newly diagnosed asthma patients who had at least one claim of inpatient admission or at least three claims of outpatient records. We enrolled 5350 montelukast users and 10700 non-users in this cohort study. The following mean (±SD) time of the Montelukast group is 5 (±2.19 )years, and the non-users group is 6.2 5.47 (± 2.641) years. By using multivariable Cox regression, our analysis indicated that the risk of incident cardiovascular diseases between montelukast users (n=43, 0.8%) and non-users (n=111, 1.04%) is approximately equal. [adjusted hazard ratio 0.992; P-value:0.9643] Conclusion: In this population-based study, we found that the use of montelukast is not associated with a decrease in incident MI or IS.

Keywords: asthma, inflammation, montelukast, insurance research database, cardiovascular diseases

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Authors: Chi-Chang Lin, Jiun-Yan Chiu

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Periodontal disease, oral cancer relating trauma is the prominent factor devastating bone tissue that is crucial to reestablishing in clinical. As we know, common symptom, osteoporosis, and infection limiting the ability of the bone tissue to recover cause difficulty before implantation therapy. Regeneration of bone tissue is the fundamental therapy before surgical processes. To promote the growth of bone tissue, many commercial products still have sophisticated problems that need to overcome. Regrettably, there is no available material which is apparently preferable for releasing and controlling of loading dosage, or mitigating inflammation. In our study, a hydrogel-based composite membrane has been prepared by using Gellan gum (GG), gamma-polyglutamic acid (γ-PGA) and glycerol with simple sol-gel method. GG is a natural material that is massively adopted in cartilage. Unfortunately, the strength of pure GG film is a manifest weakness especially under simulating body fluidic conditions. We utilize another biocompatible material, γ-PGA as cross-linker which can form tri-dimension structure that enhancing the strength. Our result indicated the strength of pure GG membrane can be obviously improved by cross-linked with γ-PGA (0.5, 0.6, 0.7, 0.8, 0.9, 1.0 w/v%). Besides, blending with glycerol (0, 1.0, 2.0, 3.0 w/v%) can significantly improve membrane toughness that corresponds to practical use. The innovative composited hydrogel made of GG, γ-PGA, and glycerol is attested with neat results including elongation and biocompatibility that take the advantage of extension covering major trauma. Recommendations are made for treatment to build up the foundation of bone tissue that would help patients to escape from the suffering and shorten the amount of time in recovery.

Keywords: bone tissue, gellan gum, regeneration, toughness

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Authors: Abbas Shafiee, Mohammad Taghi Ahmadian, Maryam Hoviattalab

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The biomechanical behavior of brain tissue is needed for predicting the traumatic brain injury (TBI). Each year over 1.5 million people sustain a TBI in the USA. The appropriate coefficients for injury prediction can be evaluated using experimental data. In this study, an experimental setup on brain soft tissue was developed to perform unconfined compression tests at quasistatic strain rates ∈0.0004 s-1 and 0.008 s-1 and 0.4 stress relaxation test under unconfined uniaxial compression with ∈ 0.67 s-1 ramp rate. The fitted visco-hyperelastic parameters were utilized by using obtained stress-strain curves. The experimental data was validated using finite element analysis (FEA) and previous findings. Also, influence of friction coefficient on unconfined compression and relaxation test and effect of ramp rate in relaxation test is investigated. Results of the findings are implemented on the analysis of a human brain under high acceleration due to impact.

Keywords: brain soft tissue, visco-hyperelastic, finite element analysis (FEA), friction, quasistatic strain rate

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Authors: Bangoura Issa, Ji-Young Kang, M. T. H. Chowdhury, Ji-Eun Lee, Yong-Ki Hong

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Investigation was carried out for the production of value-added abalone Haliotis discus hannai containing bioactive phlorotannin by feeding phlorotannin-rich seaweed Eisenia bicyclis 2 weeks prior to harvesting. Accumulation of phlorotannins was proceded by feeding with E. bicyclis after 4 days of starvation. HPLC purification afforded two major phlorotannins. Mass spectrometry and 1H-nuclear magnetic resonance analysis clarified their structures to be as 7-phloroeckol and eckol. Throughout the feeding period of 20 days, 7-phloroeckolol was accumulated in the muscle (foot muscle tissue) up to 0.18±0.12 mg g-1 dry weight of tissue after 12 days. Eckol reached 0.21±0.03 mg g-1 dry weight of tissue after 18 days. By feeding Laminaria japonica as reference, abalone showed no detection of phlorotannins in the muscle tissue. Seaweed consumption and growth rate of abalone revealed almost similar when feed with E. bicyclis or L. japonicain 20 days. Phlorotannins reduction to half-maximal accumulation values took 1.0 day and 2.7 days for 7-phloroeckol and eckol respectively, after replacing the feed to L. japonica.

Keywords: abalone, accumulation, eisenia bicyclis, phlorotannins

Procedia PDF Downloads 356