Search results for: MICE strategy

Authors: Huamin Xu, Wenting Jia, Hong Jiang, Junxia Xie

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Rosmarinic acid (RA) is a natural acid that is found in a variety of herbs, such as rosemary and has multiple biological activities such as antioxidative, anti-inflammatory and antiviral activities. In this study, we investigated the neuroprotective effects of RA on dopaminergic system in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced mouse model of Parkinson’s disease (PD). The mice received oral administration of RA before MPTP injection. Results showed that the tyrosine hydroxylase expression in SN reduced and the levels of dopamine and its metabolites in the striatum decreased in MPTP intoxicated PD mice. Pretreatment with RA significantly inhibited these changes. Further studies demonstrated that MPTP treatment increased the iron content, which was counteracted by pre-treatment with RA. In addition, RA could restore the decrease of superoxide dismutase (SOD) induced by MPTP. This study provides evidence that RA could suppress MPTP-induced degeneration of the nigrostriatal dopaminergic system by regulating iron content and the expression of SOD. Thus, RA might be clinically evaluated for the prevention of neurodegenerative diseases.

Keywords: rosmarinic acid, Parkinson's disease, MPTP, dopaminergic system

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Authors: Lindie Grebe

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This paper reports on a study that explored the strategizing practices of professional accountants in the mining industry, based on Jarratt and Stiles’ dominant strategizing practice models framework. Drawing on a strategy-as-practice perspective, the paper recognises qualified professional accountants in strategic management such as Chief Executive Officers, as strategy practitioners that perform their strategizing practices and praxis within a specific context. The main findings of this paper were produced through semi-structured individual interviews with accountants that perform strategy on a business level in the South African mining industry. Qualitative data were analysed through conversation analysis over two coding-cycles. Findings describe accountant strategists as practitioners who challenge the dominant business model when a disconnect seems to exist between international corporate level strategy and business level strategy in the South African mining industry. Accountant strategy practitioners described their dominant strategizing practice model as incremental change during strategic planning and as a lived experience during strategy implementation. Findings portrayed these strategists as taking initiative as strategy leaders in a dynamic and volatile environment to combine their accounting background with strategic management and challenge the dominant business model. Understanding how accountant strategists perform strategizing offers insight into the social practice of strategic management. This understanding contributes to the body of knowledge on strategizing in the South African mining industry. In addition, knowledge on the transformation of accountants as strategists could provide valuable practice relevant insights for accounting educators and the accounting profession alike.

Keywords: accountant strategists, dominant strategizing practice models framework, mining industry, strategy-as-practice

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Authors: Chao Jen-Chih, Kuo-Wei Hsu

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Many venues and spaces in cities gradually become old and decayed as time goes by and develops. Urban regeneration is the critical strategy to promote local development, but the method of spatial reconstruction which is emphasized in the issue of urban regeneration is questioned for bringing cultural, social and economic impacts on old city areas. The idea of “Urban Regeneration Station (URS)” is proposed for Taipei City Government to introduce the entry and disturbance of communities and related groups with the concept of creative city. This study explored how an URS promotes local development again through the strength of communities and the energy of local residence community, and it established the Platform Strategy for URS. The research results are as follows: URS through the promotion of government agencies, experts, scholars and the third sector, to the selection of different types of units stationed in business, through exhibitions, seminars, and other activities to explore local development issues, vetting each stationed execution efficiency units, and different units stationed by URS establish URS overall network platform strategy.

Keywords: urban regeneration, platform strategy, creative city, Taipei city

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Authors: Yun Zuo, Wenju Li

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Shenzhen is one of China’s gates to the world. What was once a fishing village is now a metropolis of more than 10 million people. Because of its unprecedented pace of development, it also brings a serious of issues, such as the self-renewal of the city. In the paper, we use Sungang-Quingshuihe(SQ) as an example. SQ is one of the oldest districts in the east of Shenzhen. Nowadays, SQ faces many challenges. This is because once the logistics area has been slowly disappear, the new identity will be replaced. As a result, we are to minimize damages to the city in transforming process by seeking for a new design strategy. In the meantime, we think that each district in a city has its own role forming the whole city together. Therefore, a district transformation is functionally-oriented and for improving city quality in focus.

Keywords: old district, renewal strategy, public space, sustainable development

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Authors: Maria Debora Braga, Luigi Riso, Maria Grazia Zoia

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Risk-based approaches to asset allocation are portfolio construction methods that do not rely on the input of expected returns for the asset classes in the investment universe and only use risk information. They include the Minimum Variance Strategy (MV strategy), the traditional (volatility-based) Risk Parity Strategy (SRP strategy), the Most Diversified Portfolio Strategy (MDP strategy) and, for many, the Equally Weighted Strategy (EW strategy). All the mentioned approaches were based on portfolio volatility as a reference risk measure but in 2023, the Kurtosis-based Risk Parity strategy (KRP strategy) and the Minimum Kurtosis strategy (MK strategy) were introduced. Understandably, they used the fourth root of the portfolio-fourth moment as a proxy for portfolio kurtosis to work with a homogeneous function of degree one. This paper contributes mainly theoretically and methodologically to the framework of risk-based asset allocation approaches with two steps forward. First, a new and more flexible objective function considering a linear combination (with positive coefficients that sum to one) of portfolio volatility and portfolio kurtosis is used to alternatively serve a risk minimization goal or a homogeneous risk distribution goal. Hence, the new basic idea consists in extending the achievement of typical risk-based approaches’ goals to a combined risk measure. To give the rationale behind operating with such a risk measure, it is worth remembering that volatility and kurtosis are expressions of uncertainty, to be read as dispersion of returns around the mean and that both preserve adherence to a symmetric framework and consideration for the entire returns distribution as well, but also that they differ from each other in that the former captures the “normal” / “ordinary” dispersion of returns, while the latter is able to catch the huge dispersion. Therefore, the combined risk metric that uses two individual metrics focused on the same phenomena but differently sensitive to its intensity allows the asset manager to express, in the context of an objective function by varying the “relevance coefficient” associated with the individual metrics, alternatively, a wide set of plausible investment goals for the portfolio construction process while serving investors differently concerned with tail risk and traditional risk. Since this is the first study that also implements risk-based approaches using a combined risk measure, it becomes of fundamental importance to investigate the portfolio effects triggered by this innovation. The paper also offers a second contribution. Until the recent advent of the MK strategy and the KRP strategy, efforts to highlight interesting properties of risk-based approaches were inevitably directed towards the traditional MV strategy and SRP strategy. Previous literature established an increasing order in terms of portfolio volatility, starting from the MV strategy, through the SRP strategy, arriving at the EQ strategy and provided the mathematical proof for the “equalization effect” concerning marginal risks when the MV strategy is considered, and concerning risk contributions when the SRP strategy is considered. Regarding the validity of similar conclusions when referring to the MK strategy and KRP strategy, the development of a theoretical demonstration is still pending. This paper fills this gap.

Keywords: risk parity, portfolio kurtosis, risk diversification, asset allocation

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Authors: Komal Khan, Hafsa Zaneb, Saima Masood, Muhammad Younus, Sanan Raza

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Cigarette smoke induces many physiological and pathological changes in respiratory tract like goblet cell hyperplasia and regional distention of airspaces. It is also associated with elevation of inflammatory profiles in different airway compartments. As probiotics are generally known to promote mucosal tolerance, it was postulated that prophylactic use of probiotics can be helpful in reduction of respiratory damage induced by cigarette smoke exposure. Twenty-four adult mice were randomly divided into three groups (cigarette-smoke (CS) group, cigarette-smoke+ Lactobacillus (CS+ P) group, control (Cn) group), each having 8 mice. They were exposed to cigarette smoke for 28 days (6 cigarettes/ day for 6 days/week). Wright-Giemsa staining of bronchoalveolar lavage fluid (BALF) was performed in three mice per group. Tissue samples of trachea and lungs of 7 mice from each group were processed by paraffin embedding technique for haematoxylin & eosin (H & E) and alcian blue- periodic acid-Schiff (AB-PAS) staining. Then trachea (goblet cell number, ratio and loss of cilia) and lungs (airspace distention) were studied. The results showed that the number of goblet cells was increased in CS group as a result of defensive mechanism of the respiratory system against irritating substances. This study also revealed that the cells of CS group having acidic glycoprotein were found to be higher in quantity as compared to those containing neutral glycoprotein. However, CS + P group showed a decrease in goblet cell index due to enhanced immunity by prophylactically used probiotics. Moreover, H & E stained tracheas showed significant loss of cilia in CS group due to propelling of mucous but little loss in CS + P group because of having good protective tracheal epithelium. In lungs, protection of airspaces was also much more evident in CS+ P group as compared to CS group having distended airspaces, especially at 150um distance from terminal bronchiole. In addition, a comprehensive analysis of inflammatory cells population of BALF showed neutrophilia and eosinophilia was significantly reduced in CS+ P group. This study proved that probiotics are found to be useful for reduction of changes in micro-architecture of the respiratory system. Thus, dietary supplementation of probiotic as prophylactic measure can be useful in achieving immunomodulatory effects.

Keywords: cigarette smoke, probiotics, goblet cells, airspace enlargement, BALF

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Authors: Peerawat Chailom, Pimgarn Suwan-Natada

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The objective of this study is to examine the effects of e-commerce integrated for export marketing strategy on export advantage and firm performance. This study indicates that e-commerce infrastructure, organizational learning for e-commerce, and internet dissemination were antecedent of e-commerce integrated for export marketing strategy. In additional, export expertise is moderating variable of the research. In this study, 151 export businesses in Thailand are the sample of study. The results of study indicate that e-commerce integrated for export marketing strategy has significant positive influences on export advantage and export performance. Moreover, e-commerce infrastructure, organizational learning for e-commerce, and internet dissemination are have positive effects on e-commerce integrated for export marketing strategy. For moderating effect, export expertise significant influences on the relationships between e-commerce integrated for export marketing strategy and export advantage, and significant influences on the relationships between e-commerce integrated for export marketing strategy and export performance. Theoretical and practical implications are presented. Conclusion and suggestions for future research are also discussed.

Keywords: e-commerce integrated for export marketing, e-commerce infrastructure, organizational learning for e-commerce, export performance

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Authors: Hyun June Kim, Tailong Shi, Seden Akdagli, Sam Most, Yuling Yan

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Quantitative analysis of mouse whisker movement can be used to study functional recovery and regeneration of facial nerve after an injury. However, it is challenging to accurately track mouse whisker movements, and most whisker tracking methods require manual intervention, e.g. fixing the head of the mouse during a study. Here we describe a semi-automated image processing method that is applied to high-speed video recordings of free-moving mice to track whisker movements. We first track the head movement of a mouse by delineating the lower head contour frame-by-frame to locate and determine the orientation of its head. Then, a region of interest is identified for each frame, with subsequent application of the Hough transform to track individual whisker movements on each side of the head. Our approach is used to examine the functional recovery of damaged facial nerves in mice over a course of 21 days.

Keywords: mystacial macrovibrissae, whisker tracking, head tracking, facial nerve recovery

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Authors: Christine P. Gibson, Ramona Alex, Michael Farney, Johana Vallejo-Elias, Mitra Esfandiarei

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Aortic aneurysm is the leading cause of death in Marfan syndrome (MFS), a connective tissue disorder caused by mutations in fibrillin-1 gene (FBN1). MFS aneurysm is characterized by weakening of the aortic wall due to elastin fibers fragmentation and disorganization. The above-average height and distinct physical features make young adults with MFS desirable candidates for competitive sports; but little is known about the exercise limit at which they will be at risk for aortic rupture. On the other hand, aerobic cardiovascular exercise has been shown to have protective effects on the heart and aorta. We have previously reported that mild aerobic exercise can delay the formation of aortic aneurysm in a mouse model of MFS. In this study, we aimed to investigate the effects of various levels of exercise intensity on the progression of aortic aneurysm in the mouse model. Starting at 4 weeks of age, we subjected control and MFS mice to different levels of exercise intensity (8m/min, 10m/min, 15m/min, and 20m/min, corresponding to 55%, 65%, 75%, and 85% of VO2 max, respectively) on a treadmill for 30 minutes per day, five days a week for the duration of the study. At 24 weeks of age, aortic tissue were isolated and subjected to structural and functional studies using histology and wire myography in order to evaluate the effects of different exercise routines on elastin fragmentation and organization and aortic wall elasticity/stiffness. Our data shows that exercise training at the intensity levels between 55%-75% significantly reduces elastin fragmentation and disorganization, with less recovery observed in 85% MFS group. The reversibility of elasticity was also significantly restored in MFS mice subjected to 55%-75% intensity; however, the recovery was less pronounced in MFS mice subjected to 85% intensity. Furthermore, our data shows that smooth muscle cells (SMCs) contractilion in response to vasoconstrictor agent phenylephrine (100nM) is significantly reduced in MFS aorta (54.84 ± 1.63 mN/mm2) as compared to control (95.85 ± 3.04 mN/mm2). At 55% of intensity, exercise did not rescue SMCs contraction (63.45 ± 1.70 mN/mm2), while at higher intensity levels, SMCs contraction in response to phenylephrine was restored to levels similar to control aorta [65% (81.88 ± 4.57 mN/mm2), 75% (86.22 ± 3.84 mN/mm2), and 85% (83.91 ± 5.42 mN/mm2)]. This study provides the first time evidence that high intensity exercise (e.g. 85%) may not provide the most beneficial effects on aortic function (vasoconstriction) and structure (elastin fragmentation, aortic wall elasticity) during the progression of aortic aneurysm in MFS mice. On the other hand, based on our observations, medium intensity exercise (e.g. 65%) seems to provide the utmost protective effects on aortic structure and function in MFS mice. These findings provide new insights into the potential capacity, in which MFS patients could participate in various aerobic exercise routines, especially in young adults affected by cardiovascular complications particularly aortic aneurysm. This work was funded by Midwestern University Research Fund.

Keywords: aerobic exercise, aortic aneurysm, aortic wall elasticity, elastin fragmentation, Marfan syndrome

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Authors: Nana Katsitadze, Tamar Atanelishvili, Mariam Kutateladze, Alexandre Tushishvili

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In the modern world, tourism has emerged as one of the most powerful economic sectors, and due to its high economic performance, it is attractive to the countries with various levels of economic development. The purpose of the present paper, dedicated to discussing the current problems of tourism development, is to find ways which will contribute to bringing more benefits to the country from the sector. Georgia has been successfully developing leisure tourism for the last ten years, and at the next stage of development business, tourism gains particular importance for Georgia as a means of mitigating the negative socio-economic effects caused by the seasonality of tourism and as a high-cost tourism market. Therefore, the object of the paper is to study the factors that contribute to the development of business tourism. The paper uses the research methods such as system analysis, synthesis, analogy, as well as historical, comparative, economic, and statistical methods of analysis. The information base for the research is made up of the statistics on the functioning of the tourism market of Georgia and foreign countries as well as official data provided by international organizations in the field of tourism. Based on the experience of business tourism around the world and identifying the successful start of business tourism development in Georgia and its causing factors, a business tourism development model for Georgia has been developed. The model might be useful as a methodological material for developing a business tourism development concept for the countries with limited financial resources but rich in tourism resources like Georgia. On the initial stage of development (in absence of conventional centers), the suggested concept of business tourism development involves organizing small and medium-sized meetings both in large cities and in regions by using high-class hotel infrastructure and event management services. Relocation of small meetings to the regions encourages inclusive development of the sector based on increasing the awareness of these regions as tourist sites as well as the increase in employment and sales of other tourism or consumer products. Business tourism increases the number of hotel visitors in the non-seasonal period and improves hotel performance indicators, which enhances the attractiveness of investing in the hotel business. According to the present concept of business tourism development, at the initial stage, development of business tourism is based on the existing markets, including internal market, neighboring markets and the markets of geographically relatively near countries and at the next stage, the concept involves generating tourists from other relatively distant target markets. As a result, by gaining experience in business tourism, enhancing professionalism, increasing awareness and stimulating infrastructure development, the country will prepare the basis to move to a higher stage of tourism development. In addition, the experience showed that for attracting large customers, peculiarities of the field require activation of state policy and active use of marketing mechanisms and tools of the state.

Keywords: hotel industry development, MICE model, MICE strategy, MICE tourism in Georgia

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Authors: Johanrik, Arini Apriliani, Fikri Haikal, Dias Yuca, Muhammad Abdul Latif, Edijanti Goenarwo, Nurita Pratama Sari

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Diarrhea is one of the leading causes of morbidity and mortality in many countries, as well as responsible for the deaths of millions of people each year. Previous research showed that the leaves, bark, and root bark of kedondong contains saponins, tannins, and flavonoids. Tannins have anti-diarrheal effects that work as the freeze of protein/astringent, and may inhibit the secretion of chloride over the tannate bonding between protein in the intestines. Chemical compounds of flavonoids also have an effect as anti-diarrheal block receptors Cl ˉ in intestinal thus reducing the secretion of Cl ˉ to the intestinal lume .This research aims to know the anti-diarrheal activity of extracts kedondong leaf in mice Balb/C strain males in vivo. This research also proves kedondong leaves as an anti-diarrhea through trial efficacy of kedondong leaves as antisekretori and antimotilitas. This research using post-test only controlled group design. Analysis of statistical data normality and homogenity were tested by Kolmogorov Smirnov. If the data obtained homogenous then using ANOVA test. This research using ethanolic extracts kedondong leaf 200, 400 and 800 mg/kgBW to prove there is anti-diarrhea it makes into six treatment groups, for anti-secretory it makes into five treatment groups and anti-motility became five treatment groups. The result showed dose of ethanolic extracts kedondong leaf 800 mg/kgBW have significant value (p<0.005). The conclusion from this extracts kedondong leaf research 800 mg/kgBW have pharmacological effects as antidiarrhea on Balb/C strain male mice with a mechanism of action as anti-secretory and anti-motility.

Keywords: anti-diarrhea, anti-secretory, anti-motility, kedondong leaf

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Authors: Aurelija Burinskiene

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This paper presents the study for an e-commerce warehouse. The study is aiming to improve order fulfillment activity by identifying the strategy presenting the best performance. A simulation model was proposed to reach the target of this research. This model enables various scenario tests in an e-commerce warehouse, allowing them to find out for the best order fulfillment strategy. By using simulation, model authors investigated customers’ orders representing on-line purchases for one month. Experiments were designed to evaluate various order picking methods applicable to the fulfillment of customers’ orders. The research uses cost components analysis and helps to identify the best possible order picking method improving the overall performance of e-commerce warehouse and fulfillment service to the customers. The results presented show that the application of order batching strategy is the most applicable because it brings distance savings of around 6.7 percentage. This result could be improved by taking an assortment clustering action until 8.34 percentage. So, the recommendations were given to apply the method for future e-commerce warehouse operations.

Keywords: e-commerce, order, fulfilment, strategy, simulation

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Authors: Zahra F. Al-Khateeb, Shenel Shekerzade, Hasna Boumenar, Siân M. Henson, Jordi L. Tremoleda, A. T. Michael-Titus

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Traumatic brain injury (TBI) is the leading cause of disability and death in young adults and also increases the risk ofneurodegeneration. The mechanisms linking moderate to severe TBI to neurodegeneration are not known. It has been proposed that cellular senescence inductionpost-injury could amplify neuroinflammation and induce long-term changes. The impact of these processes after injury to an immature brain has not been characterised yet. We carried out a controlled cortical impact injury (CCI) in juvenile 1 month-old male CD1 mice. Animals were anesthetised and received a unilateral CCI injury. The sham group received anaesthesia and had a craniotomy. A naïve group had no intervention. The brain tissue was analysed at 5 days and 35 days post-injury using immunohistochemistry and markers for microglia, astrocytes, and senescence. Compared tonaïve animals, injured mice showed an increased microglial and astrocytic reaction early post-injury, as reflected in Iba1 and GFAP markers, respectively; the GFAP increase persisted in the later phase. The senescence analysis showed a significant increase inγH2AX-53BP1 nuclear foci, 8-oxoguanine, p19ARF, p16INK4a, and p53 expression in naïve vs. sham groups and naïve vs. CCI groups, at 5 dpi. At 35 days, the difference was no longer statistically significant in all markers. The injury induced a decrease p21 expression vs. the naïve group, at 35 dpi. These results indicate the induction of a complex senescence response after immature brain injury. Some changes occur early and may reflect the activation/proliferation of non-neuronal cells post-injury that had been hindered, whereas changes such as p21 downregulation may reflect a delayed response and pro-repair processes.

Keywords: cellular senescence, traumatic brain injury, brain injury, controlled cortical impact

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Authors: Mahnaz Zarein, Hamed Shoorei

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Background: Malathion is one of the most toxic agents widely used in agriculture throughout the world. This agent has adverse effects on the functions of multiple organs such as the reproductive system in both male and female genders. On the one hand, daily use of antioxidant supplementations such as hesperidin is capable to neutralize the deleterious impacts of malathion. Therefore, in this experimental study, the protective effects of hesperidin against ovarian toxicity induced by malathion were investigated. Material & Methods: Balb/c adult mice (n=32) were randomly divided into 4 groups including 1) the control group, treated with normal saline, 2) the Mal group, treated with 30mg/kg malathion, daily for 1 month, 3) Mal + Hes group, treated with 20 mg/kg malathion and 20 mg/kg hesperidin, daily for 1 month, and 5) Hes group, treated with 20 mg/kg hesperidin. At the end of the experimental period, mice were anesthetized and their drops of blood were collected to the assessment of some hormones such as LH, FSH, E2, and P4. Also, the right ovaries were used to H&E staining, and the left ovaries were used for IHC staining (PCNA and FSHR). Results: Histopathological assessments showed that the number of follicles, i.e. primordial, primary, and secondary, significantly decreased, while the atretic follicle counts remarkably increased compared to the control group (p<0.05). Hormonal levels revealed that the production of all mentioned hormones decreased in the Mal group in comparison with the control group (p<0.05). The expression of PCNA, as a proliferative marker, and FHSR, as a marker showing maturation, decreased when mice received malathion compared to the control group (p<0.05). Interestingly, treatment with hesperidin significantly neutralized the adverse effects of malathion on all mentioned parameters. Conclusion: Daily use of antioxidant supplementations such as hesperidin could alleviate the ovarian toxicity induced by malathion.

Keywords: malathion, ovary, antioxidant hesperidin, FSHR PCNA, ovary

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Authors: Maryam Goodarzi, Mahdieh Sheikhi, Mehdi Goodarzi

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This study intends to offer an appropriate strategy development framework for a telecommunication firm (as a case study) which works on Information and Communication Technology (ICT) projects, development of telecommunication networks, and maintenance of local networks, according to its dominant condition. In this approach, first, the objectives were set and the mission was defined. Then, the capability was assessed by SWOT matrix. Using SPACE matrix, the strategy of the company was determined. The strategic direction is set and an appropriate and superior strategy was developed and offered employing QSPM matrix. The theoretical framework or conceptual model of the present study first involves 4 stages of framework development and then from stage 3 (assessing capability) onward, a strategic management model by Fred R. David. In this respect, the tools and methods offered in the framework are appropriate for all kinds of organizations, particularly small firms, and help strategists identify, evaluate, and select strategies.

Keywords: strategy formulation, firm mission, strategic direction, space diagram, quantitative strategic planning matrix, SWOT matrix

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Authors: Ieva Bruzauskaite, Jovile Raudoniute, Karina Poliakovaite, Danguole Zabulyte, Daiva Bironaite, Ruta Aldonyte

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Introduction: Air pollution is a growing global problem which has been shown to be responsible for various adverse health outcomes. Immunotoxicity, such as dysregulated inflammation, has been proposed as one of the main mechanisms in air pollution-associated diseases. Chronic obstructive pulmonary disease (COPD) is among major morbidity and mortality causes worldwide and is characterized by persistent airflow limitation caused by the small airways disease (obstructive bronchiolitis) and irreversible parenchymal destruction (emphysema). Exact pathways explaining the air pollution induced and mediated disease states are still not clear. However, modern societies understand dangers of polluted air, seek to mitigate such effects and are in need for reliable biomarkers of air pollution. We hypothesise that post-translational modifications of structural proteins, e.g. citrullination, might be a good candidate biomarker. Thus, we have designed this study, where mice were exposed to diesel exhaust and the ongoing protein modifications and inflammation in lungs and other tissues were assessed. Materials And Methods: To assess the effects of diesel exhaust a in vivo study was designed. Mice (n=10) were subjected to everyday 2-hour exposure to diesel exhaust for 14 days. Control mice were treated the same way without diesel exhaust. The effects within lung and other tissues were assessed by immunohistochemistry of formalin-fixed and paraffin-embedded tissues. Levels of inflammation and citrullination related markers were investigated. Levels of parenchymal damage were also measured. Results: In vivo study corroborates our own data from in vitro and reveals diesel exhaust initiated inflammatory shift and modulation of lung peptidyl arginine deiminase 4 (PAD4), citrullination associated enzyme, levels. In addition, high levels of citrulline were observed in exposed lung tissue sections co-localising with increased parenchymal destruction. Conclusions: Subacute exposure to diesel exhaust renders mice lungs inflammatory and modifies certain structural proteins. Such structural changes of proteins may pave a pathways to lost/gain function of affected molecules and also propagate autoimmune processes within the lung and systemically.

Keywords: air pollution, citrullination, in vivo, lungs

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Authors: C. Panebianco, K. Adamberg, S. Adamberg, C. Saracino, M. Jaagura, K. Kolk, A. Di Chio, P. Graziano, R. Vilu, V. Pazienza

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Background/Aims: Despite recent advances in treatment options, a modest impact on the outcome of the pancreatic cancer (PC) is observed so far. Short-term fasting cycles have the potential to improve the efficacy of chemotherapy against PC. However, diseased people may refuse to follow the fasting regimen and fasting may worsen the weight loss often occurring in cancer patients. Therefore, alternative approaches are needed. The aim of this study was to assess the effect of Engineered Low glycemic food ELGIF mimicking diet on growth of cancer cell lines in vitro and in an in vivo pancreatic cancer mouse xenograft model. Materials and Methods: BxPC-3, MiaPaca-2 and Panc-1 cells were cultured in control and ELGIF mimicking diet culturing condition to evaluate the tumor growth and proliferation pathways. Pancreatic cancer xenograft mice were subjected to ELGIF to assess the tumor volume and weight as compared to mice fed with control diet. Results: Pancreatic cancer cells cultured in ELGIF mimicking medium showed decreased levels of proliferation as compared to those cultured in the standard medium. Consistently, xenograft pancreatic cancer mice subjected to ELGIF diet displayed a significant decrease in tumor growth. Conclusion: A positive effect of ELGIF diet on proliferation in vitro is associated with the decrease of tumor progression in the in vivo PC xenograft mouse model. These results suggest that engineered dietary interventions could be supportive as synergistic approach to enhance the efficacy of existing cancer treatments in pancreatic cancer patients.

Keywords: functional food, microbiota, mouse model, pancreatic cancer

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Authors: Suliman Khan, Rabeea Siddique, Mengzhou Xue

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Background: Patients with neurological disorders often display altered circadian rhythms. The disrupted circadian rhythms through chronic jetlag or shiftwork are thought to increase the risk and severity of human disease, including cancer, psychiatric, and related brain diseases. In this study, we investigated the impact of shiftwork or chronic jetlag (CJL) like conditions on mice’s brains. Transcriptome profiling based on RNA sequencing revealed that genes associated with serious neurological disorders were differentially expressed in the nucleus accumbens (NAc) and prefrontal cortex (PFC). According to the qPCR analysis, several key regulatory genes associated with neurological disorders were significantly altered in the NAc, PFC, hypothalamus, hippocampus, and striatum. Serotonin levels and the expression levels of serotonin transporters and receptors were significantly altered in mice treated with CJL. Overall, these results indicate that CJL may increase the risk of neurological disorders by disrupting the key regulatory genes, biological functions, serotonin, and corticosterone. These molecular linkages can further be studied to investigate the mechanism underlying CJL or shiftwork-mediated neurological disorders in order to develop treatment strategies.

Keywords: chronic jetlag, molecular profiles, brain disorders, circadian rhythms

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Authors: Bo-Huei Huang, Chih-Hsun Yang, Meng-Tsan Tsai

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Optical coherence tomography (OCT) enables to provide advantages of noninvasive imaging, high resolution, and high imaging speed. In this study, we integrated OCT and a CW laser for tumor diagnosis and treatment. The axial and transverse resolutions of the developed OCT system are 3 μm and 1 μm, respectively. The frame rate of OCT system is 30 frames/s. In this study, the tumor cells were implanted into the mice skin and scanned by OCT to observe the morphological and angiographic changes. With OCT imaging, 3D microstructures and skin angiography of mice skin can be simultaneously acquired, which can be utilized for identification of the tumor distribution. Then, the CW laser beam can be accurately controlled to expose on the center of the tumor, according to the OCT results. Moreover, OCT was used to monitor the induced photothermolysis and to evaluate the treatment outcome. The results showed that OCT-guided laser therapy could efficiently improve the treatment outcome and the extra damage induced by CW can be greatly reduced. Such OCT-guided laser therapy system could be a potential tool for dermatological applications.

Keywords: optical coherence tomography, laser therapy, skin tumor, position guide

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Authors: Sara Pereira-Nogueira, Tim Worbs, Marc Permanyer-Bosser, Reinhold Förster

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While the entry mechanism of lymphocytes into the lymph node via the blood are well described, it is still largely unknown how cells enter lymph nodes that arrive via afferent lymphatics. In order to address this, our group has established a micro-injection technique in mice through which cells are delivered directly into the lymphatic vessel immediately afferent to the popliteal lymph node. Injected cells can then be tracked via multi-colour fluorescence or 2-photon microscopy, and their localization can be analysed within the popliteal or downstream lymph nodes by immunohistology. Since naïve B cells express the chemokine receptor CXCR5 we intra-lymphatically co-injected B cells derived from wildtype and Cxcr5-deficient mice. While CXCR5 does not play a role in guiding B cells out of the subcapsular sinus, it affects their positioning within the lymph node parenchyma, since CXCR5-deficient B cells are impaired in migrating into the B cell follicle. The knowledge obtained by studying B-cell migration may prove beneficial in clinical settings regarding tumor metastasis or autoimmune diseases.

Keywords: afferent lymphatics, B cell migration, chemokine, intra-lymphatic injection

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Authors: Horia Păunescu

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Purpose: The study aimed to assess the depressant or antidepressant effects of several Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) in mice: the selective cyclooxygenase-2 (COX-2) inhibitor meloxicam, and the non-selective COX-1 and COX-2 inhibitors lornoxicam, sodium metamizole, and ketorolac. The current literature data regarding such effects of these agents are scarce. Materials and methods: The study was carried out on NMRI mice weighing 20-35 g, kept in a standard laboratory environment. The study was approved by the Ethics Committee of the University of Medicine and Pharmacy „Carol Davila”, Bucharest. The study agents were injected intraperitoneally, 10 mL/kg body weight (bw) 1 hour before the assessment of the locomotor activity by cage testing (n=10 mice/ group) and 2 hours before the forced swimming tests (n=15). The study agents were dissolved in normal saline (meloxicam, sodium metamizole), ethanol 11.8% v/v in normal saline (ketorolac), or water (lornoxicam), respectively. Negative and positive control agents were also given (amitryptilline in the forced swimming test). The cage floor used in the locomotor activity assessment was divided into 20 equal 10 cm squares. The forced swimming test involved partial immersion of the mice in cylinders (15/9cm height/diameter) filled with water (10 cm depth at 28C), where they were left for 6 minutes. The cage endpoint used in the locomotor activity assessment was the number of treaded squares. Four endpoints were used in the forced swimming test (immobility latency for the entire 6 minutes, and immobility, swimming, and climbing scores for the final 4 minutes of the swimming session), recorded by an observer that was "blinded" to the experimental design. The statistical analysis used the Levene test for variance homogeneity, ANOVA and post-hoc analysis as appropriate, Tukey or Tamhane tests.Results: No statistically significant increase or decrease in the number of treaded squares was seen in the locomotor activity assessment of any mice group. In the forced swimming test, amitryptilline showed an antidepressant effect in each experiment, at the 10 mg/kg bw dosage. Sodium metamizole was depressant at 100 mg/kg bw (increased the immobility score, p=0.049, Tamhane test), but not in lower dosages as well (25 and 50 mg/kg bw). Ketorolac showed an antidepressant effect at the intermediate dosage of 5 mg/kg bw, but not so in the dosages of 2.5 and 10 mg/kg bw, respectively (increased the swimming score, p=0.012, Tamhane test). Meloxicam and lornoxicam did not alter the forced swimming endpoints at any dosage level. Discussion: 1) Certain NSAIDs caused changes in the forced swimming patterns without interfering with locomotion. 2) Sodium metamizole showed a depressant effect, whereas ketorolac proved antidepressant. Conclusion: NSAID-induced mood changes are not class effects of these agents and apparently are independent of the type of inhibited cyclooxygenase (COX-1 or COX-2). Disclosure: This paper was co-financed from the European Social Fund, through the Sectorial Operational Programme Human Resources Development 2007-2013, project number POSDRU /159 /1.5 /S /138907 "Excellence in scientific interdisciplinary research, doctoral and postdoctoral, in the economic, social and medical fields -EXCELIS", coordinator The Bucharest University of Economic Studies.

Keywords: antidepressant, depressant, forced swim, NSAIDs

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Authors: M. Mousavi-Daramoroudi, H. Yousefnia, F. Abbasi-Davani, S. Zolghadri, S. Kakaei

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Despite the appropriate characteristics of ¹⁷⁷Lu and DOTATOC, to our best knowledge, the therapeutic benefit of ¹⁷⁷Lu-DOTATOC complex in breast cancer has not been reported until now. In this study, biodistribution of ¹⁷⁷Lu-DOTA-TOC in mouse tumor model for evaluation of possible utilization of this complex in breast cancer treatment was investigated.¹⁷⁷Lu was prepared with the specific activity of 2.6-3 GBq.mg^-1 and radionuclidic purity higher than 99%. The radiolabeled complex was prepared in the optimized conditions with the radiochemical purity higher than 99%. The final solution was injected to the BALB/c mice with adenocarcinoma breast cancer. The biodistribution results showed major accumulation in the kidneys as the major excretion route and the somatostatin receptor-positive tissues such as pancreas compared with the other tissues. Also, significant uptake was observed in tumor even in longer time after injection. According to the results obtained in this research study, somatostatin receptors expressed in breast cancers can be targeted with DOTATOC analogues especially with ¹⁷⁷Lu-DOTATOC as an ideal therapeutic agent.

Keywords: ¹⁷⁷Lu, adenocarcinoma breast cancer, DOTATOC, BALB/c mice

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Authors: Dilek Ozturk, Narin Ozturk, Zeliha Pala Kara, Engin Kaptan, Serap Sancar Bas, Nurten Ozsoy, Alper Okyar

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Most physiological processes oscillate in a rhythmic manner in mammals including metabolism and energy homeostasis, locomotor activity, hormone secretion, immune and endocrine system functions. Endocrine body rhythms are tightly regulated by the circadian timing system. The hypothalamic-pituitary-thyroid (HPT) axis is under circadian control at multiple levels from hypothalamus to thyroid gland. Since circadian timing system controls a variety of biological functions in mammals, circadian rhythms of biological functions may modify the drug tolerability/toxicity depending on the dosing time. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer agent that is active against many cancers. It was also found to be active in medullary thyroid cancer. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus on the thyroid gland and hormones in mice. Healthy C57BL/6J mice were synchronized with 12h:12h Light-Dark cycle (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding to Light onset). Everolimus was administered to male (5 mg/kg/day) and female mice (15 mg/kg/day) orally at ZT1-rest period- and ZT13-activity period- for 4 weeks; body weight loss, clinical signs and possible changes in serum thyroid hormone levels (TSH and free T4) were examined. Histological alterations in the thyroid gland were evaluated according to the following criteria: follicular size, colloid density and viscidity, height of the follicular epithelium and the presence of necrotic cells. The statistical significance between differences was analyzed with ANOVA. Study findings included everolimus-related diarrhea, decreased activity, decreased body weight gains, alterations in serum TSH levels, and histopathological changes in thyroid gland. Decreases in mean body weight gains were more evident in mice treated at ZT1 as compared to ZT13 (p < 0.001, for both sexes). Control tissue sections of thyroid glands exhibited well-organized histoarchitecture when compared to everolimus-treated groups. Everolimus caused histopathological alterations in thyroid glands in male (5 mg/kg, slightly) and female mice (15 mg/kg; p < 0.01 for both ZT as compared to their controls) irrespective of dosing-time. TSH levels were slightly decreased upon everolimus treatment at ZT13 in both males and females. Conversely, increases in TSH levels were observed when everolimus treated at ZT1 in both males (5 mg/kg; p < 0.05) and females (15 mg/kg; slightly). No statistically significant alterations in serum free T4 levels were observed. TSH and free T4 is clinically important thyroid hormones since a number of disease states have been linked to alterations in these hormones. Serum free T4 levels within the normal ranges in the presence of abnormal serum TSH levels in everolimus treated mice may suggest subclinical thyroid disease which may have repercussions on the cardiovascular system, as well as on other organs and systems. Our study has revealed the histological damage on thyroid gland induced by subacute everolimus administration, this effect was irrespective of dosing time. However, based on the body weight changes and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13 in both male and females. Yet, effects of everolimus on thyroid functions may deserve further studies regarding their clinical importance and chronotoxicity.

Keywords: circadian rhythm, chronotoxicity, everolimus, thyroid gland, thyroid hormones

Procedia PDF Downloads 349

Authors: G. Erkomaishvili

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The paper discusses economic policy of Georgia aiming to increase national competitiveness as well as the tools and means which will help to improve the competitiveness of the country. The sectors of the economy, in which the country can achieve the competitive advantage, are studied. It is noted that the country’s economic policy plays an important role in obtaining and maintaining the competitive advantage - authority should take measures to ensure high level of education; scientific and research activities should be funded by the state; foreign direct investments should be attracted mainly in science-intensive industries; adaptation with the latest scientific achievements of the modern world and deepening of scientific and technical cooperation. Stable business environment and export oriented strategy is the basis for the country’s economic growth. As the outcome of the research, the paper suggests the strategy for improving competitiveness in Georgia; recommendations are provided based on relevant conclusions.

Keywords: competitive advantage, competitiveness, competitiveness improvement strategy, competitiveness of Georgia

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Authors: Rozo D. Juan Felipe, Ramírez L. Leonardo Juan, Puerta A. Gabriel Alberto

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The telemedicine services require correct computing resource management to guarantee productivity and efficiency for medical and non-medical staff. The aim of this study was to examine web management strategies to ensure the availability of resources and services in telemedicine so as to provide medical information management with an accessible strategy. In addition, to evaluate the quality-of-service parameters, the followings were measured: delays, throughput, jitter, latency, available bandwidth, percent of access and denial of services based of web management performance map with profiles permissions and database management. Through 24 different test scenarios, the results show 100% in availability of medical information, in relation to access of medical staff to web services, and quality of service (QoS) of 99% because of network delay and performance of computer network. The findings of this study suggest that the proposed strategy of web management is an ideal solution to guarantee the availability, reliability, and accessibility of medical information. Finally, this strategy offers seven user profile used at telemedicine center of Bogota-Colombia keeping QoS parameters suitable to telemedicine services.

Keywords: availability, medical information, QoS, strategy, telemedicine

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Authors: T. Martini, J. M. Martínez

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An algorithmic acceleration strategy based on quasi-Newton (or secant) methods is displayed for address the practical problem of accelerating the convergence of the Newton-Lagrange method in the case of convergence to critical multipliers. Since the Newton-Lagrange iteration converges locally at a linear rate, it is natural to conjecture that quasi-Newton methods based on the so called secant equation and some minimal variation principle, could converge superlinearly, thus restoring the convergence properties of Newton's method. This strategy can also be applied to accelerate the convergence of algorithms applied to fixed-points problems. Computational experience is reported illustrating the efficiency of this strategy to solve fixed-point problems with linear convergence rate.

Keywords: algorithmic acceleration, fixed-point problems, nonlinear programming, quasi-newton method

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Authors: Chung-Young Lee, Se-Hee Ahn, Jun-Gu Choi, Youn-Jeong Lee, Hyuk-Joon Kwon, Jae-Hong Kim

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A/chicken/Korea/01310/2001 (H9N2) (01310) was passaged through embryonated chicken eggs (ECEs) by 20 times (01310-E20), and it has been used for an inactivated oil emulsion vaccine in Korea. After sequential passages, 01310-E20 showed higher pathogenicity in ECEs and acquired multiple mutations including a potential N-glycosylation at position 133 (H3 numbering) in HA and 18aa-deletion in NA stalk. To evaluate the effect of these mutations on the mammalian pathogenicity and resistance to non-specific inhibitors, we generated four PR8-derived recombinant viruses with different combinations of HA and NA from 01310-E2 and 01310-E20 (rH2N2, rH2N20, rH20N2, and rH20N20). According to our results, recombinant viruses containing 01310 E20 HA showed higher growth property in MDCK cells and higher virulence on mice than those containing 01310 E2 HA regardless of NA. The hemagglutination activity of rH20N20 was less inhibited by egg white and mouse lung extract than that of other recombinant viruses. Thus, the increased pathogenicity of 01310-E20 may be related to both higher replication efficiency and resistance to non-specific inhibitors in mice.

Keywords: avian influenza virus, egg adaptation, H9N2, N-glycosylation, stalk deletion of neuraminidase

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Authors: Jun Liu, Feihang Zhou, Gungyi Wang

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This paper expounds on the direct-driven PMSG wind power system control strategy, and analyses the stability conditions of the system. The direct-driven PMSG wind power system may generate the intense mechanical vibration, when wind speed changes dramatically. This paper proposes a new type of torque control strategy, which increases the system damping effectively, mitigates mechanical vibration of the system, and enhances the stability conditions of the system. The simulation results verify the reliability of the new torque control strategy.

Keywords: damping, direct-driven PMSG wind power system, mechanical vibration, torque control

Procedia PDF Downloads 333

Authors: P. J. Sweeney, T. Ahtoniemi, J. Puoliväli, T. Laitinen, K. Lehtimäki, A. Nurmi, D. Wells

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Duchenne muscular dystrophy (DMD) is caused by an X linked mutation in the dystrophin gene; lack of dystrophin causes a progressive muscle necrosis which leads to a progressive decrease in mobility in those suffering from the disease. The MDX mouse, a mutant mouse model which displays a frank dystrophinopathy, is currently widely employed in pre clinical efficacy models for treatments and therapies aimed at DMD. In general the end-points examined within this model have been based on invasive histopathology of muscles and serum biochemical measures like measurement of serum creatine kinase (sCK). It is established that a “critical period” between 4 and 6 weeks exists in the MDX mouse when there is extensive muscle damage that is largely sub clinical but evident with sCK measurements and histopathological staining. However, a full characterization of the MDX model remains largely incomplete especially with respect to the ability to aggravate of the muscle damage beyond the critical period. The purpose of this study was to attempt to aggravate the muscle damage in the MDX mouse and to create a wider, more readily translatable and discernible, therapeutic window for the testing of potential therapies for DMD. The study consisted of subjecting 15 male mutant MDX mice and 15 male wild-type mice to an intense chronic exercise regime that consisted of bi-weekly (two times per week) treadmill sessions over a 12 month period. Each session was 30 minutes in duration and the treadmill speed was gradually built up to 14m/min for the entire session. Baseline plasma creatine kinase (pCK), treadmill training performance and locomotor activity were measured after the “critical period” at around 10 weeks of age and again at 14 weeks of age, 6 months, 9 months and 12 months of age. In addition, kinematic gait analysis was employed using a novel analysis algorithm in order to compare changes in gait and fine motor skills in diseased exercised MDX mice compared to exercised wild type mice and non exercised MDX mice. In addition, a morphological and metabolic profile (including lipid profile), from the muscles most severely affected, the gastrocnemius muscle and the tibialis anterior muscle, was also measured at the same time intervals. Results indicate that by aggravating or exacerbating the underlying muscle damage in the MDX mouse by exercise a more pronounced and severe phenotype in comes to light and this can be picked up earlier by kinematic gait analysis. A reduction in mobility as measured by open field is not apparent at younger ages nor during the critical period, but changes in gait are apparent in the mutant MDX mice. These gait changes coincide with pronounced morphological and metabolic changes by non-invasive anatomical MRI and proton spectroscopy (1H-MRS) we have reported elsewhere. Evidence of a progressive asymmetric pathology in imaging parameters as well as in the kinematic gait analysis was found. Taken together, the data show that chronic exercise regime exacerbates the muscle damage beyond the critical period and the ability to measure through non-invasive means are important factors to consider when performing preclinical efficacy studies in the MDX mouse.

Keywords: Gait, muscular dystrophy, Kinematic analysis, neuromuscular disease

Procedia PDF Downloads 276

Authors: Hye Jin Choi, Mirim Jin, Jeong June Choi

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Green tea, which is one of the most popular of tea, contains various ingredients that help health. Epigallocatechin gallate (EGCG) is one of the main active polyphenolic compound possessing diverse biologically beneficial effects such as anti-oxidation, anti-cancer founding in green tea. This study was performed to investigate the anti-diabetic effect of high-purity EGCG ( > 98%) in a spontaneous diabetic mellitus animal model, db/db mouse. Four-week-old male db/db mice, which was induced to diabetic mellitus by the high-fat diet, were orally administered with high-purity EGCG (10, 50 and 100 mg/kg) for 4 weeks. Daily weight and diet efficiency were examined, and blood glucose level was assessed once a week. After 4 weeks of EGCG administration, fasting blood glucose level was measured. Then, the mice were sacrificed and total abdominal fat was sampled to examine the change in fat weight. Plasma was separated from the blood and the levels of aspartate amino-transferase (ALT) and alanine amino-transferase (AST) were investigated. As results, blood glucose and body weight were significantly decreased by EGCG treatment compared to the control group. Also, the amount of abdominal fat was down-regulated by EGCG. However, ALT and AST levels, which are indicators of liver function, were similar to those of control group. Taken together, our study suggests that high purity EGCG is capable of treating diabetes mellitus based in db / db mice with safety and has a potent to develop a therapeutics for metabolic disorders. This work was supported by Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry (IPET) through High Value-added Food Technology Development Program, funded by Ministry of Agriculture, Food and Rural Affairs (MAFRA) (317034-03-2-HD030)

Keywords: anti-diabetic effect, db/db mouse, diabetes mellitus, green tea, epigallocatechin gallate

Procedia PDF Downloads 187