Search results for: drug policy
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 5706

Search results for: drug policy

4476 Market-Driven Process of Brain Circulation in Knowledge Services Industry in Sri Lanka

Authors: Panagodage Janaka Sampath Fernando

Abstract:

Brain circulation has become a buzzword in the skilled migration literature. However, promoting brain circulation; returning of skilled migrants is challenging. Success stories in Asia, for instances, Taiwan, and China, are results of rigorous policy interventions of the respective governments. Nonetheless, the same policy mix has failed in other countries making it skeptical to attribute the success of brain circulation to the policy interventions per se. The paper seeks to answer whether the success of brain circulation within the Knowledge Services Industry (KSI) in Sri Lanka is a policy driven or a market driven process. Mixed method approach, which is a combination of case study and survey methods, was employed. Qualitative data derived from ten case studies of returned entrepreneurs whereas quantitative data generated from a self-administered survey of 205 returned skilled migrants (returned skilled employees and entrepreneurs) within KSI. The pull factors have driven the current flow of brain circulation within KSI but to a lesser extent, push factors also have influenced. The founding stone of the industry has been laid by a group of returned entrepreneurs, and the subsequent growth of the industry has attracted returning skilled employees. Sri Lankan government has not actively implemented the reverse brain drain model, however, has played a passive role by creating a peaceful and healthy environment for the industry. Therefore, in contrast to the other stories, brain circulation within KSI has emerged as a market driven process with minimal government interventions. Entrepreneurs play the main role in a market-driven process of brain circulation, and it is free from the inherent limitations of the reverse brain drain model such as discriminating non-migrants and generating a sudden flow of low-skilled migrants. Thus, to experience a successful brain circulation, developing countries should promote returned entrepreneurs by creating opportunities in knowledge-based industries.

Keywords: brain circulation, knowledge services industry, return migration, Sri Lanka

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4475 Rejuvenating the Water Edge: An Urban Design Initiative for Waterways. Case: Kottayam – Chenganassery, Kerala

Authors: Aswathy Rajagopal

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Many research agendas addressed interesting questions concerning the extent and character of water transport and many others looked at various phenomenon of urban waterfront development. The paper explore to highlight the importance of Inland Water Transportation(IWT) and the need for further development of IWT regulatory framework and for synergy between the inland navigation institutions both at policy and expert levels by taking the Backwater system of Kerala, India as the demonstration site. The author seeks to highlight the hurdles faced in integrating water transportation, the interchange between water and land and the waterfront development. The aim of the research is to look at the tools and methods that can be applied for waterfront regeneration and end with suggestions for policies and design considerations to guide the physical development along the proposed Kottayam –Chenganassery arterial waterway.

Keywords: waterways, inland water transportation (IWT), urban policy, waterfront development, Kerala backwaters

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4474 Circular Economy in Social Practice in Response to Social Needs: Community Actions Versus Government Policy

Authors: Sai-Kit Choi

Abstract:

While traditional social services heavily depended on Government funding and support, there were always time lag, and resources mismatch with the fast growing and changing social needs. This study aims at investigating the effectiveness of implementing Circular Economy concept in a social service setting with comparison to Government Policy in response to social needs in 3 areas: response time, suitability, and community participation. To investigate the effectiveness of implementing Circular Economy concept in a social service setting, a real service model, a community resources sharing platform, was set up and statistics of the first 6 months’ operation data were used as comparison with traditional social services. Literature review was conducted as a reference basis of traditional social services under Government Policy. Case studies were conducted to provide the qualitative perspectives of the innovative approach. The results suggest that the Circular Economy model showed extraordinarily high level of community participation. In addition, it could utilize community resources in response precisely to the burning social needs. On the other hand, the available resources were unstable when comparing to those services supported by Government funding. The research team concluded that Circular Economy has high potential in applications in social service, especially in certain areas, such as resources sharing platform. Notwithstanding, it should be aware of the stability of resources when the services targeted to support some crucial needs.

Keywords: circular economy, social innovation, community participation, sharing economy, social response

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4473 Sexual Health and Sexual Risk Behavior of the Youth with HIV Positive in Northeastern Part, Thailand

Authors: Orathai Srithongtham, Ubonsri Thabuddha

Abstract:

The youth with HIV positive is not difference from the general youth in term of sexual needs. Sexual health is crucial the most to support the youth with HIV positive to be sexual well-being. This study aims to elucidate the sexual health on protection from STDs (Sexual Transmitted Diseases) and HIV transmission and to explain sexual risk behavior of the youth with HIV positive. The target group was the youth with HIV positive about 23 cases from two provinces in northeastern part of Thailand. Qualitative method was applied for collecting data by in-depth interview. Content analysis was use for data analysis. The youth with HIV positive was protection from STDs and HIV transmission by using the condom during sexual activity. The reason to deny the condom use were ashamed, condom is not a part of life, no have fit size, and the youth fear to stigmatized as a mental disorder and fear to stigmatized as going to fuck someone. The youth who trust with nurse in clinic was dare to request the condom by face. Sexual activity without condom use is sexual risk behavior. The major causes were couple trust and the sexual enjoyment first and sexual active competition with friend without condom use. The concern on HIV was the boyfriend or girlfriend not accepts the HIV positive people, worry about the HIV transmutation, and finally not compliance to ARV drug. The youth with HIV positive was lacking of the knowledge on sexual health on the issues of access to condom and the concern to keep on relationship with the boyfriend or girlfriend. This concern issues was led to the non-adherence of ARV drug and HIV distribution. To provide the sexual health service is more essential to the youth with HIV positive.

Keywords: sexual health, sexual risk behavior, youth, HIV

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4472 Exploring Factors Affecting Electricity Production in Malaysia

Authors: Endang Jati Mat Sahid, Hussain Ali Bekhet

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Ability to supply reliable and secure electricity has been one of the crucial components of economic development for any country. Forecasting of electricity production is therefore very important for accurate investment planning of generation power plants. In this study, we aim to examine and analyze the factors that affect electricity generation. Multiple regression models were used to find the relationship between various variables and electricity production. The models will simultaneously determine the effects of the variables on electricity generation. Many variables influencing electricity generation, i.e. natural gas (NG), coal (CO), fuel oil (FO), renewable energy (RE), gross domestic product (GDP) and fuel prices (FP), were examined for Malaysia. The results demonstrate that NG, CO, and FO were the main factors influencing electricity generation growth. This study then identified a number of policy implications resulting from the empirical results.

Keywords: energy policy, energy security, electricity production, Malaysia, the regression model

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4471 Accelerated Molecular Simulation: A Convolution Approach

Authors: Jannes Quer, Amir Niknejad, Marcus Weber

Abstract:

Computational Drug Design is often based on Molecular Dynamics simulations of molecular systems. Molecular Dynamics can be used to simulate, e.g., the binding and unbinding event of a small drug-like molecule with regard to the active site of an enzyme or a receptor. However, the time-scale of the overall binding event is many orders of magnitude longer than the time-scale of simulation. Thus, there is a need to speed-up molecular simulations. In order to speed up simulations, the molecular dynamics trajectories have to be ”steared” out of local minimizers of the potential energy surface – the so-called metastabilities – of the molecular system. Increasing the kinetic energy (temperature) is one possibility to accelerate simulated processes. However, with temperature the entropy of the molecular system increases, too. But this kind ”stearing” is not directed enough to stear the molecule out of the minimum toward the saddle point. In this article, we give a new mathematical idea, how a potential energy surface can be changed in such a way, that entropy is kept under control while the trajectories are still steared out of the metastabilities. In order to compute the unsteared transition behaviour based on a steared simulation, we propose to use extrapolation methods. In the end we mathematically show, that our method accelerates the simulations along the direction, in which the curvature of the potential energy surface changes the most, i.e., from local minimizers towards saddle points.

Keywords: extrapolation, Eyring-Kramers, metastability, multilevel sampling

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4470 The Pharmacogenetics of Type 1 Cannabinoid Receptor (CB1) Gene Associated with Adverse Drug Reactions in Thai Patients

Authors: Kittitara Chunlakittiphan, Patompong Satapornpong

Abstract:

Introduction: The variation of genetics affects how our body responds to pharmaceuticals elucidates the correlation between long-term use of medical cannabis and adverse drug reactions (ADRs). Medical cannabis is regarded as the treatment for chronic pain, cancer pain, acute pain, psychological disorders, multiple sclerosis and migraine management. However, previous studies have shown that delta-9-Tetrahydrocannabinol (THC), an ingredient found in cannabis, was the cause of ADRs in CB1 receptors found in humans. Previous research suggests that distributions of the cannabinoid type 1 (CB1) receptor gene and pharmacogenetic markers, which vary amongst different populations, might affect incidences of ADRs. Although there is an evident need to investigate the level of the CB1 receptor gene (rs806365), studies on the distribution of CB1-pharmacogenetics markers in Thai patients are limited. Objective: Therefore, the aim of this study is to investigate the distribution of the rs806365 polymorphism in Thai patients who have been treated with medical cannabis. Materials and Methods: We enrolled 31 Thai patients with THC-induced ADRs and 34 THC-tolerant controls to take part in this study. All patients with THC-induced ADRs were accessed through a review of medical records by physicians. EDTA blood of 3ml was collected to obtain the CNR1 gene (rs806365) and genotyping of this gene was conducted using the real-time PCR ViiA7 (ABI, Foster City, CA, USA) following the manufacturer’s instruction. Results: The sample consisted of 65 patients (40/61.54%) were females and (25/38.46%) were males, with an age range of 19-87 years, who have been treated with medical cannabis. In this study, the most common THC-induced ADRs were dry mouth and/or dry throat, tachycardia, nausea, and arrhythmia. Across the whole sample, we found that 52.31% of Thai patients carried a heterozygous variant (rs806365, CT allele). Moreover, the number of rs806365 (CC, homozygous variant) carriers totaled seventeen people (26.15%) amongst the subjects of Thai patients treated with medical cannabis. Furthermore, 17 out of 22 patients (77.27%) who experienced severe ADRs: Tachycardia and/or arrhythmia, carried an abnormal rs806365 gene (CT and CC alleles). Conclusions: The results propose that the rs806365 gene is widely distributed amongst the Thai population and there is a link between this gene and vulnerability to developing THC-induced ADRs after being treated with medical cannabis. Therefore, it is necessary to screen for the rs806365 gene before using medical cannabis to treat a patient.

Keywords: rs806365, THC-induced adverse drug reactions, CB1 receptor, Thai population

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4469 Evaluation of Trabectedin Safety and Effectiveness at a Tertiary Cancer Center at Qatar: A Retrospective Analysis

Authors: Nabil Omar, Farah Jibril, Oraib Amjad

Abstract:

Purpose: Trabecatine is a is a potent marine-derived antineoplastic drug which binds to the minor groove of the DNA, bending DNA towards the major groove resulting in a changed conformation that interferes with several DNA transcription factors, repair pathways and cell proliferation. Trabectedin was approved by the European Medicines Agency (EMA; London, UK) for the treatment of adult patients with advanced stage soft tissue sarcomas in whom treatment with anthracyclines and ifosfamide has failed, or for those who are not candidates for these therapies. The recommended dosing regimen is 1.5 mg/m2 IV over 24 hours every 3 weeks. The purpose of this study was to comprehensively review available data on the safety and efficacy of trabectedin used as indicated for patients at a Tertiary Cancer Center at Qatar. Methods: A medication administration report generated in the electronic health record identified all patients who received trabectedin between November 1, 2015 and November 1, 2017. This retrospective chart review evaluated the indication of trabectedin use, compliance to administration protocol and the recommended monitoring parameters, number of patients improved on the drug and continued treatment, number of patients discontinued treatment due to side-effects and the reported side effects. Progress and discharged notes were utilized to report experienced side effects during trabectedin therapy. A total of 3 patients were reviewed. Results: Total of 2 out of 3 patients who received trabectedin were receiving it for non-FDA and non-EMA, approved indications; metastatic rhabdomyosarcoma and ovarian cancer stage IV with poor prognosis. And only one patient received it as indicated for leiomyosarcoma of left ureter with metastases to liver, lungs and bone. None of the patients has continued the therapy due to development of serious side effects. One patient had stopped the medication after one cycle due to disease progression and transient hepatic toxicity, the other one had disease progression and developed 12 % reduction in LVEF after 12 cycles of trabectedin, and the third patient deceased, had disease progression on trabectedin after the 10th cycle that was received through peripheral line which resulted in developing extravasation and left arm cellulitis requiring debridement. Regarding monitoring parameters, at baseline the three patients had ECHO, and Creatine Phosphokinase (CPK) but it was not monitored during treatment as recommended. Conclusion: Utilizing this medication as indicated with performing the appropriate monitoring parameters as recommended can benefit patients who are receiving it. It is important to reinforce the intravenous administration via central intravenous line, the re-assessment of left ventricular ejection fraction (LVEF) by echocardiogram or multigated acquisition (MUGA) scan at 2- to 3-month intervals thereafter until therapy is discontinued, and CPK and LFTs levels prior to each administration of trabectedin.

Keywords: trabectedin, drug-use evaluation, safety, effectiveness, adverse drug reaction, monitoring

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4468 Bullying with Neurodiverse Students and Education Policy Reform

Authors: Fharia Tilat Loba

Abstract:

Studies show that there is a certain group of students who are more vulnerable to bullying due to their physical appearance, disability, sexual preference, race, and lack of social and behavioral skills. Students with autism spectrum disorders (ASD) are one of the most vulnerable groups among these at-risk groups. Researchers suggest that focusing on vulnerable groups of students who can be the target of bullying helps to understand the causes and patterns of aggression, which ultimately helps in structuring intervention programs to reduce bullying. Since Australia ratified the United Nations Convention on the Rights of Persons with Disabilities in 2006, it has been committed to providing an inclusive, safe, and effective learning environment for all children. In addition, the 2005 Disability Standards for Education seeks to ensure that students with disabilities can access and participate in education on the same basis as other students, covering all aspects of education, including harassment and victimization. However, bullying hinders students’ ability to fully participate in schooling. The proposed study aims to synthesize the notions of traditional bullying and cyberbullying and attempts to understand the experiences of students with ASD who are experiencing bullying in their schools. The proposed study will primarily focus on identifying the gaps between policy and practice related to bullying, and it will also attempt to understand the experiences of parents of students with ASD and professionals who have experience dealing with bullying at the school level in Australia. This study is expected to contribute to the theoretical knowledge of the bullying phenomenon and provide a reference for advocacy at the school, organization, and government levels.

Keywords: education policy, bullying, Australia, neurodiversity

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4467 The Strategy for Increasing the Competitiveness of Georgia

Authors: G. Erkomaishvili

Abstract:

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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4466 Magnitude and Outcome of Resuscitation Activities at Rwanda Military Hospital for the Period of April 2013-September 2013

Authors: Auni Idi Muhire

Abstract:

Background: Prior to April 2012, resuscitations were often ineffective resulting in poor patient outcomes. An initiative was implemented at Rwanda Military Hospital (RMH) to review root causes and plan strategies to improve patient outcomes. An interdisciplinary committee was developed to review this problem. Purpose: Analyze the frequency, obstacles, and outcome of patient resuscitation following cardiac and/or respiratory arrest. Methods: A form was developed to allow recording of all actions taken during resuscitation including response times, staff present, and equipment and medications used. Results:-The patient population requiring the most resuscitation effort are the intensive care patients, most frequently the neonatal the intensive care patients (42.8%) -Despite having trained staff representatives, not all resuscitations follow protocol -Lack of compliance with drug administration guidelines was noted, particularly in initiating use of drugs despite the drug being available (59%). Lesson Learned: Basic Life Support training for interdisciplinary staff resulted in more effective response to cardiac and/or respiratory arrest at RMH. Obstacles to effective resuscitation included number of staff, knowledge and skill level of staff, availability of appropriate equipment and medications, staff communication, and patient Do not Attempt Resuscitation (DNR) status.

Keywords: resuscitation, case analysis of knowledge versus practice, intensive care, critical care

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4465 Agroecology Approaches Towards Sustainable Agriculture and Food System: Reviewing and Exploring Selected Policies and Strategic Documents through an Agroecological Lens

Authors: Dereje Regasa

Abstract:

The global food system is at a crossroads, which requires prompt action to minimize the effects of the crises. Agroecology is gaining prominence due to its contributions to sustainable food systems. To support efforts in mitigating the crises, the Food and Agriculture Organization (FAO) established alternative approaches for sustainable agri-food systems. Agroecological elements and principles were developed to guide and support measures that countries need to achieve the Sustainable Development Goals (SDGs). The SDGs require the systemic integration of practices for a smart intensification or adaptation of traditional or industrial agriculture. As one of the countries working towards SDGs, the agricultural practices in Ethiopia need to be guided by these agroecological elements and principles. Aiming at the identification of challenging aspects of a sustainable agri-food system and the characterization of an enabling environment for agroecology, as well as exploring to what extent the existing policies and strategies support the agroecological transition process, five policy and strategy documents were reviewed. These documents are the Rural Development Policy and Strategy, the Environment Policy, the Biodiversity Policy, and the Soil Strategy of the Ministry of Agriculture (MoA). Using the Agroecology Criteria Tool (ACT), the contents were reviewed, focusing on agroecological requirements and the inclusion of sustainable practices. ACT is designed to support a self-assessment of elements supporting agroecology. For each element, binary values were assigned based on the inclusion of the minimum requirements index and then validated through discussion with the document owners. The results showed that the documents were well below the requirements for an agroecological transition of the agri-food system. The Rural Development Policy and Strategy only suffice to 83% in Human and Social Value. It does not support the transition concerning the other elements. The Biodiversity Policy and Soil Strategy suffice regarding the inclusion of Co-creation and Sharing of knowledge (100%), while the remaining elements were not considered sufficiently. In contrast, the Environment Policy supports the transition with three elements accounting for 100%. These are Resilience, Recycling, and Human and Social Care. However, when the four documents were combined, elements such as Synergies, Diversity, Efficiency, Human and Social value, Responsible governance, and Co-creation and Sharing of knowledge were identified as fully supportive (100%). This showed that the policies and strategies complemented one another to a certain extent. However, the evaluation results call for improvements concerning elements like Culture and food traditions, Circular and solidarity economy, Resilience, Recycling, and Regulation and balance since the majority of the elements were not sufficiently observed. Consequently, guidance for the smart intensification of local practices is needed, as well as traditional knowledge enriched with advanced technologies. Ethiopian agricultural and environmental policies and strategies should provide sufficient support and guidance for the intensification of sustainable practices and should provide a framework for an agroecological transition towards a sustainable agri-food system.

Keywords: agroecology, diversity, recycling, sustainable food system, transition

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4464 Values That Should Be Taken into Account in the Arts: The Tension between Economic Influences and Cultural Values

Authors: Mohammad Mehdi Mazaheri, Mohammad Motiee Lahromi

Abstract:

Recently the two matters of how to evaluate art and what the influencing economic effects on cultural values are have attracted many researchers to investigate them. Therefore, in the present article the researcher made an attempt to answer the above questions. However, the fundamental distinction between this article and the other ones is in comparing the economic value (shown by monetary phrases) with cultural values (that reflects the aesthetic values and the importance of the artist). This article shows a different and trivial distinction that has a very clearly pivotal significance in the process of cultural policy making. The economic activities would be influenced when there are cultural values. The increase of commercial activities is measured by impact assessment. In other words, the value of culture is reflected in the satisfaction of the users of cultural activities. This kind of value is measured by “willingness to pay” researches. The researcher believes that these two values are dominant in the cultural policy but they include many aspects and are presented by different kinds of communities.

Keywords: economic influence, cultural values, monetary phrases, aesthetic values

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4463 Indoor and Outdoor Health Risk Factors as a Result of Smoke Emission in Developing Countries: a Case of Nigeria

Authors: Beatrice Adeoye

Abstract:

Background: One of the health challenges developing countries face is air pollution from indoor and outdoor activities. Smoke as a result of cooking, burning wastes and power generators litter the air space on a continual basis due to poverty and governance challenges. The short and long term implications of these actions are enormous and studies have attributed smoke as one of the leading preventable risk factors contributing to global burden of respiratory infections. Design/Methods: The issue at hand therefore includes an exploration of the existing policy frameworks regarding smoke, adherence to international conventions and practices, and more importantly the activities of the government in addressing these issues. Aside this, an understanding of the implications of smoke on peoples’ health and well-being also become crucial. Consequently, this article seeks to interrogate the effect of smoke on the health and well-being of Nigerians and the activities of the policy makers in addressing these challenges. Results (Main Argument): This study reviewed both primary and secondary data on poverty, smoke emission and attendant health risks coupled with existing policies on smoke and air pollution in the country. For instance, over 69% of Nigerians are poor, ranking third in the world; 2.9 billion people live in homes using wood, coal or dung as their primary cooking fuel; equally, 50.6% of Nigerians has no access to regular electricity supply. Further, sustainable policy regarding smoke emission is lacking in the country. This work further submitted that continued low standard of living as a result of governance challenges coupled with a lack of sustainable policy have aggravated the health risks related to smoke in the country. Conclusions: The implication on the health of the children, mothers and vulnerable groups for the future of the country is enormous and may continue if not addressed. Urgent attention therefore needs to be focused on this area considering what this portends for the nation now and in the future.

Keywords: air pollution, indoor, outdoor, respiratory infections

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4462 Biomimetic Systems to Reveal the Action Mode of Epigallocatechin-3-Gallate in Lipid Membrane

Authors: F. Pires, V. Geraldo, O. N. Oliveira Jr., M. Raposo

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Catechins are powerful antioxidants which have attractive properties useful for tumor therapy. Considering their antioxidant activity, these molecules can act as a scavenger of the reactive oxygen species (ROS), alleviating the damage of cell membrane induced by oxidative stress. The complexity and dynamic nature of the cell membrane compromise the analysis of the biophysical interactions between drug and cell membrane and restricts the transport or uptake of the drug by intracellular targets. To avoid the cell membrane complexity, we used biomimetic systems as liposomes and Langmuir monolayers to study the interaction between catechin and membranes at the molecular level. Liposomes were formed after the dispersion of anionic 1,2-dipalmitoyl-sn-glycero-3-[phospho-rac-(1-glycerol)(sodium salt) (DPPG) phospholipids in an aqueous solution, which mimic the arrangement of lipids in natural cell membranes and allows the entrapment of catechins. Langmuir monolayers were formed after dropping amphiphilic molecules, DPPG phospholipids, dissolved in an organic solvent onto the water surface. In this work, we mixed epigallocatechin-3-gallate (EGCG) with DPPG liposomes and exposed them to ultra-violet radiation in order to evaluate the antioxidant potential of these molecules against oxidative stress induced by radiation. The presence of EGCG in the mixture decreased the rate of lipid peroxidation, proving that EGCG protects membranes through the quenching of the reactive oxygen species. Considering the high amount of hydroxyl groups (OH groups) on structure of EGCG, a possible mechanism to these molecules interact with membrane is through hydrogen bonding. We also investigated the effect of EGCG at various concentrations on DPPG Langmuir monolayers. The surface pressure isotherms and infrared reflection-absorption spectroscopy (PM-IRRAS) results corroborate with absorbance results preformed on liposome-model, showing that EGCG interacts with polar heads of the monolayers. This study elucidates the physiological action of EGCG which can be incorporated in lipid membrane. These results are also relevant for the improvement of the current protocols used to incorporate catechins in drug delivery systems.

Keywords: catechins, lipid membrane, anticancer agent, molecular interactions

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4461 Comparative Public Administration: A Case Study of ASEAN Member States

Authors: Nattapol Pourprasert

Abstract:

This research is to study qualitative research having two objectives: 1. to study comparison of private sector of government to compare with ASEAN Member States, 2. to study trend of private enterprise administration of ASEAN Member States. The results are: (1) Thai people focus on personal resource administrative system, (2) Indonesia focuses on official system by good administrative principles, (3) Malaysia focuses on technology development to service people, (4) Philippines focuses on operation system development, (5) Singapore focuses on public service development, (6) Brunei Darussalam focuses on equality in government service of people, (7) Vietnam focuses on creating government labor base and develop testing and administration of operation test, (8) Myanmar focuses on human resources development, (9) Laos focuses on form of local administration, (10) Cambodia focuses on policy revolution in personal resources. The result of the second part of the study are: (1) Thailand created government personnel to be power under qualitative official structural event, (2) Indonesia has Bureaucracy Reform Roadmap of Bureaucracy Reform and National Development Plan Medium Term, (3) Malaysia has database for people service, (4) Philippines follows up control of units operation by government policy, (5) Singapore created reliability, participation of people to set government policy people’s demand, (6) Brunei Darussalam has social welfare to people, (7) Vietnam revolved testing system and administration including manpower base construction of government effectively, (8) Myanmar creates high rank administrators to develop country, (9) Laos distributes power to locality, and (10) Cambodia revolved personnel resource policy.

Keywords: public administration development, ASEAN member states, private sector, government

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4460 Development of Wound Dressing System Based on Hydrogel Matrix Incorporated with pH-Sensitive Nanocarrier-Drug Systems

Authors: Dagmara Malina, Katarzyna Bialik-Wąs, Klaudia Pluta

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The growing significance of transdermal systems, in which skin is a route for systemic drug delivery, has generated a considerable amount of data which has resulted in a deeper understanding of the mechanisms of transport across the skin in the context of the controlled and prolonged release of active substances. One of such solutions may be the use of carrier systems based on intelligent polymers with different physicochemical properties. In these systems, active substances, e.g. drugs, can be conjugated (attached), immobilized, or encapsulated in a polymer matrix that is sensitive to specific environmental conditions (e.g. pH or temperature changes). Intelligent polymers can be divided according to their sensitivity to specific environmental stimuli such as temperature, pH, light, electric, magnetic, sound, or electromagnetic fields. Materials & methods—The first stage of the presented research concerned the synthesis of pH-sensitive polymeric carriers by a radical polymerization reaction. Then, the selected active substance (hydrocortisone) was introduced into polymeric carriers. In a further stage, bio-hybrid sodium alginate/poly(vinyl alcohol) – SA/PVA-based hydrogel matrices modified with various carrier-drug systems were prepared with the chemical cross-linking method. The conducted research included the assessment of physicochemical properties of obtained materials i.e. degree of hydrogel swelling and degradation studies as a function of pH in distilled water and phosphate-buffered saline (PBS) at 37°C in time. The gel fraction represents the insoluble gel fraction as a result of inter-molecule cross-linking formation was also measured. Additionally, the chemical structure of obtained hydrogels was confirmed using FT-IR spectroscopic technique. The dynamic light scattering (DLS) technique was used for the analysis of the average particle size of polymer-carriers and carrier-drug systems. The nanocarriers morphology was observed using SEM microscopy. Results & Discussion—The analysis of the encapsulated polymeric carriers showed that it was possible to obtain the time-stable empty pH-sensitive carrier with an average size 479 nm and the encapsulated system containing hydrocortisone with an average 543 nm, which was introduced into hydrogel structure. Bio-hybrid hydrogel matrices are stable materials, and the presence of an additional component: pH-sensitive carrier – hydrocortisone system, does not reduce the degree of cross-linking of the matrix nor its swelling ability. Moreover, the results of swelling tests indicate that systems containing higher concentrations of the drug have a slightly higher sorption capacity in each of the media used. All analyzed materials show stable and statically changing swelling values in simulated body fluids - there is no sudden fluid uptake and no rapid release from the material. The analysis of FT-IR spectra confirms the chemical structure of the obtained bio-hybrid hydrogel matrices. In the case of modifications with a pH-sensitive carrier, a much more intense band can be observed in the 3200-3500 cm⁻¹ range, which most likely originates from the strong hydrogen interactions that occur between individual components.

Keywords: hydrogels, polymer nanocarriers, sodium alginate/poly(vinyl alcohol) matrices, wound dressings.

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4459 Epigenetic Drugs for Major Depressive Disorder: A Critical Appraisal of Available Studies

Authors: Aniket Kumar, Jacob Peedicayil

Abstract:

Major depressive disorder (MDD) is a common and important psychiatric disorder. Several clinical features of MDD suggest an epigenetic basis for its pathogenesis. Since epigenetics (heritable changes in gene expression not involving changes in DNA sequence) may underlie the pathogenesis of MDD, epigenetic drugs such as DNA methyltransferase inhibitors (DNMTi) and histone deactylase inhibitors (HDACi) may be useful for treating MDD. The available literature indexed in Pubmed on preclinical drug trials of epigenetic drugs for the treatment of MDD was investigated. The search terms we used were ‘depression’ or ‘depressive’ and ‘HDACi’ or ‘DNMTi’. Among epigenetic drugs, it was found that there were 3 preclinical trials using HDACi and 3 using DNMTi for the treatment of MDD. All the trials were conducted on rodents (mice or rats). The animal models of depression that were used were: learned helplessness-induced animal model, forced swim test, open field test, and the tail suspension test. One study used a genetic rat model of depression (the Flinders Sensitive Line). The HDACi that were tested were: sodium butyrate, compound 60 (Cpd-60), and valproic acid. The DNMTi that were tested were: 5-azacytidine and decitabine. Among the three preclinical trials using HDACi, all showed an antidepressant effect in animal models of depression. Among the 3 preclinical trials using DNMTi also, all showed an antidepressant effect in animal models of depression. Thus, epigenetic drugs, namely, HDACi and DNMTi, may prove to be useful in the treatment of MDD and merit further investigation for the treatment of this disorder.

Keywords: DNA methylation, drug discovery, epigenetics, major depressive disorder

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4458 Analyzing the Impact of Local and International Artists in Creating Cultural Identity through Public Art: Case Study of Chicago Public Policies

Authors: Kaesha M. Freyaldenhoven

Abstract:

Chicago is a city in the United States whose cultural identity is largely shaped by public art pieces. Quintessential public works created by internationally renown artists – such as Anish Kapoor’s Cloud Gate in Millennium Park and 'The Picasso' in Daley Plaza – have historically contributed to developing a shared sense of community. In 2017, the city implemented a policy titled 50x50 Neighborhood Arts Project under the Chicago Public Art Plan. The policy promotes investments in contemporary public art to elevate neighborhood cultural assets and create a sense of place. Exclusively community-based artists were commissioned to accomplish the mission of the policy. Administrators felt only local artists would be capable of capturing the true essence of a neighborhood through art. This paper discusses the relationship between the public art and the culture of its respective neighborhood through close examination of aesthetic formal properties and social significance. Research compares the role of international artists with the role of local artists in cultivating the identity of a city through site-specific artworks in Chicago. Methodology unites theoretical research on understanding art and its function in the public space with empirical research on Chicago-based works. Theoretical frameworks provide an art historical foundation to explore the manner in which physical properties convey meaning through the work itself and its placement in an urban setting. Empirical research that examines policy documentation and press announcements released by the Department of Cultural Affairs and Special Events investigates project selection processes pertaining to the artists and neighborhoods. Ethnographies and interviews of individuals from diverse social segments in contemporary Chicago society measure impacts of the works on respective populations. Findings demonstrate works created by local artists activate neighborhoods and inculcate a sense of pride among community residents. Works created by international artists garner widespread media attention that frames the city’s cultural identity across temporal and geographic zones. This research can be utilized to inform future cultural policies pertaining to the commission of public art.

Keywords: Chicago, cultural policy, public art, urban art

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4457 In vitro and in vivo Anticancer Activity of Nanosize Zinc Oxide Composites of Doxorubicin

Authors: Emma R. Arakelova, Stepan G. Grigoryan, Flora G. Arsenyan, Nelli S. Babayan, Ruzanna M. Grigoryan, Natalia K. Sarkisyan

Abstract:

Novel nanosize zinc oxide composites of doxorubicin obtained by deposition of 180 nm thick zinc oxide film on the drug surface using DC-magnetron sputtering of a zinc target in the form of gels (PEO+Dox+ZnO and Starch+NaCMC+Dox+ZnO) were studied for drug delivery applications. The cancer specificity was revealed both in in vitro and in vivo models. The cytotoxicity of the test compounds was analyzed against human cancer (HeLa) and normal (MRC5) cell lines using MTT colorimetric cell viability assay. IC50 values were determined and compared to reveal the cancer specificity of the test samples. The mechanistic study of the most active compound was investigated using Flow cytometry analyzing of the DNA content after PI (propidium iodide) staining. Data were analyzed with Tree Star FlowJo software using cell cycle analysis Dean-Jett-Fox module. The in vivo anticancer activity estimation experiments were carried out on mice with inoculated ascitic Ehrlich’s carcinoma at intraperitoneal introduction of doxorubicin and its zinc oxide compositions. It was shown that the nanosize zinc oxide film deposition on the drug surface leads to the selective anticancer activity of composites at the cellular level with the range of selectivity index (SI) from 4 (Starch+NaCMC+Dox+ZnO) to 200 (PEO(gel)+Dox+ZnO) which is higher than that of free Dox (SI = 56). The significant increase in vivo antitumor activity (by a factor of 2-2.5) and decrease of general toxicity of zinc oxide compositions of doxorubicin in the form of the above mentioned gels compared to free doxorubicin were shown on the model of inoculated Ehrlich's ascitic carcinoma. Mechanistic studies of anticancer activity revealed the cytostatic effect based on the high level of DNA biosynthesis inhibition at considerable low concentrations of zinc oxide compositions of doxorubicin. The results of studies in vitro and in vivo behavior of PEO+Dox+ZnO and Starch+NaCMC+Dox+ZnO composites confirm the high potential of the nanosize zinc oxide composites as a vector delivery system for future application in cancer chemotherapy.

Keywords: anticancer activity, cancer specificity, doxorubicin, zinc oxide

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4456 Decentralized Forest Policy for Natural Sal (Shorea robusta) Forests Management in the Terai Region of Nepal

Authors: Medani Prasad Rijal

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The study outlines the impacts of decentralized forest policy on natural Sal (shorea robusta) forests in the Terai region of Nepal. The government has implemented community forestry program to manage the forest resources and improve the livelihood of local people collectively. The forest management authorities such as conserve, manage, develop and use of forest resources were shifted to the local communities, however, the ownership right of the forestland retained by the government. Local communities took the decision on harvesting, distribution, and sell of forest products by fixing the prices independently. The local communities were putting the low value of forest products and distributed among the user households on the name of collective decision. The decision of low valuation is devaluating the worth of forest products. Therefore, the study hypothesized that decision-making capacities are equally prominent next to the decentralized policy and program formulation. To accomplish the study, individual to group level discussions and questionnaire survey methods were applied with executive committee members and user households. The study revealed that the local intuition called Community Forest User Group (CFUG) committee normally took the decisions on consensus basis. Considering to the access and affording capacity of user households having poor economic backgrounds, low pricing mechanism of forest products has been practiced, even though the Sal timber is far expensive in the local market. The local communities thought that low pricing mechanism is accessible to all user households from poor to better off households. However, the analysis of forest products distribution opposed the assumption as most of the Sal timber, which is the most valuable forest product of community forest only purchased by the limited households of better economic conditions. Since the Terai region is heterogeneous by socio-economic conditions, better off households always have higher affording capacity and possibility of taking higher timber benefits because of low price mechanism. On the other hand, the minimum price rate of forest products has poor contribution in community fund collection. Consequently, it has poor support to carry out poverty alleviation activities to poor people. The local communities have been fixed Sal timber price rate around three times cheaper than normal market price, which is a strong evidence of forest product devaluation itself. Finally, the study concluded that the capacity building of local executives as the decision-makers of natural Sal forests is equally indispensable next to the policy and program formulation for effective decentralized forest management. Unilateral decentralized forest policy may devaluate the forest products rather than devolve of power to the local communities and empower to them.

Keywords: community forestry program, decentralized forest policy, Nepal, Sal forests, Terai

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4455 Electrophoretic Changes in Testis and Liver of Mice after Exposure to Diclofenac Sodium

Authors: Deepak Mohan, Sushma Sharma, Mohammad Asif

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Diclofenac sodium being one of the most common non-steroidal anti-inflammatory drugs is normally used as painkiller and to reduce inflammation. The drug is known to alter the enzymatic activities of acid and alkaline phosphatase, glutamate oxaloacetate transaminase and glutamate pyruvate transaminases. The drug also results in change in the concentration of proteins and lipids in the body. The present study is an attempt to study different biochemical changes electrophoretically due to administration of different doses of diclofenac (4mg/kg/body weight and 14mg/kg/body weight) on liver and testes of mice from 7-28 days of investigation. Homogenization of the tissue was done, supernatant separated was loaded in the gel and native polyacrylamide gel electrophoresis was conducted. Diclofenac administration resulted in alterations of all these biochemical parameters which were observed in native polyacrylamide gel electrophoretic studies. The severe degenerative changes as observed during later stages of the experiment showed correlation with increase or decrease in the activities of all the enzymes studied in the present investigation. Image analysis of gel in liver showed a decline of 7.4 and 5.3 % in low and high dose group after 7 days whereas a decline of 9.6 and 7.5% was registered after 28 days of investigation. Similar analysis for testis also showed an appreciable decline in the activity of alkaline phosphatase after 28 days. Gel analysis of serum was also performed to find a correlation in the enzymatic activities between the tissue and blood.

Keywords: diclofenac, inflammation, polyacrylamide, phosphatase

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4454 Role of Collaborative Cultural Model to Step on Cleaner Energy: A Case of Kathmandu City Core

Authors: Bindu Shrestha, Sudarshan R. Tiwari, Sushil B. Bajracharya

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Urban household cooking fuel choice is highly influenced by human behavior and energy culture parameters such as cognitive norms, material culture and practices. Although these parameters have a leading role in Kathmandu for cleaner households, they are not incorporated in the city’s energy policy. This paper aims to identify trade-offs to transform resident behavior in cooking pattern towards cleaner technology from the questionnaire survey, observation, mapping, interview, and quantitative analysis. The analysis recommends implementing a Collaborative Cultural Model (CCM) for changing impact on the neighborhood from the policy level. The results showed that each household produces 439.56 kg of carbon emission each year and 20 percent used unclean technology due to low-income level. Residents who used liquefied petroleum gas (LPG) as their cooking fuel suffered from an energy crisis every year that has created fuel hoarding, which ultimately creates more energy demand and carbon exposure. In conclusion, the carbon emission can be reduced by improving the residents’ energy consumption culture. It recommended the city to use holistic action of changing habits as soft power of collaboration in two-way participation approach within residents, private sectors, and government to change their energy culture and behavior in policy level.

Keywords: energy consumption pattern, collaborative cultural model, energy culture, fuel stacking

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4453 Jointly Optimal Statistical Process Control and Maintenance Policy for Deteriorating Processes

Authors: Lucas Paganin, Viliam Makis

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With the advent of globalization, the market competition has become a major issue for most companies. One of the main strategies to overcome this situation is the quality improvement of the product at a lower cost to meet customers’ expectations. In order to achieve the desired quality of products, it is important to control the process to meet the specifications, and to implement the optimal maintenance policy for the machines and the production lines. Thus, the overall objective is to reduce process variation and the production and maintenance costs. In this paper, an integrated model involving Statistical Process Control (SPC) and maintenance is developed to achieve this goal. Therefore, the main focus of this paper is to develop the jointly optimal maintenance and statistical process control policy minimizing the total long run expected average cost per unit time. In our model, the production process can go out of control due to either the deterioration of equipment or other assignable causes. The equipment is also subject to failures in any of the operating states due to deterioration and aging. Hence, the process mean is controlled by an Xbar control chart using equidistant sampling epochs. We assume that the machine inspection epochs are the times when the control chart signals an out-of-control condition, considering both true and false alarms. At these times, the production process will be stopped, and an investigation will be conducted not only to determine whether it is a true or false alarm, but also to identify the causes of the true alarm, whether it was caused by the change in the machine setting, by other assignable causes, or by both. If the system is out of control, the proper actions will be taken to bring it back to the in-control state. At these epochs, a maintenance action can be taken, which can be no action, or preventive replacement of the unit. When the equipment is in the failure state, a corrective maintenance action is performed, which can be minimal repair or replacement of the machine and the process is brought to the in-control state. SMDP framework is used to formulate and solve the joint control problem. Numerical example is developed to demonstrate the effectiveness of the control policy.

Keywords: maintenance, semi-Markov decision process, statistical process control, Xbar control chart

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4452 Clarification of Taxonomic Confusions among Adulterated Drugs Coffee Seena and Seena Weed through Systematic and Pharmaceutical Markers

Authors: Shabnum Shaheen, Nida Haroon, Farah Khan, Sumera Javad, Mehreen Jalal, Samina Sarwar

Abstract:

Coffee Senna is pharmaceutically very important and used for multiple health disorders such as gastric pains, indigestion, snakebites, asthma and fever, tuberculosis and menstrual problems. However, its immense medicinal value and great demand lead to adulteration issue which could be injurious for users. Some times its adulterant Seena weed (Senna occidentalis L.) is used as its substitute which definitely not as effective as Coffee Senna. Hence, the present study was undertaken to provide some tools for systematic and pharmaceutical authentication of a shrubby plant Coffee Senna (Cassia occidentalis Linn.). These parameters included macro and micro morphological characters, anatomical and palynomorph characterization, solubility, fluorescence and phytochemical analysis. By the application of these parameters acquired results revealed that, these two plants are distinct from each other. The Coffee Seena was found to be an annual shrub with trilobed pollen, diacytic, paracytic and anisocytic stomata whereas the Seena weed stands out as an annual or perennial herb with spheroidal and circular pollen and paracytic type of stomata. The powdered drug of Coffee seena is dark grayish green whereas the powdered drug of Seena weed is light green in color. These findings are constructive in authentic identification of these plants.

Keywords: coffee senna, Senna weed, taxonomic evaluation, pharmaceutical markers

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4451 Water Safety Strategies by Service: A Study of Implementation Studies

Authors: Prince Amartey

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Water is critical to public health, quality of life, environmental preservation, economic activity, and long-term growth. In this environment, it is critical to ensure the ongoing improvement of all processes and practices that contribute to the quality and safety of water. Water safety plans (WSPs) developed by water companies are an essential public policy instrument for achieving these objectives. This manuscript examines international evidence of water safety planning adoption and implementation and reports on the current situation in Portugal as part of the necessary adaptation of the national legal framework to the publication of the Directive on water quality for human consumption. The goal is to take lessons from various successful WSP projects throughout the world while writing new legislation in Ghana and elsewhere. According to the findings, four crucial aspects and key factors of success in establishing and implementing WSPs exist commitment from leadership, technical proficiency, administration, and cooperation among agencies.

Keywords: safe drinking, risk, policy, implementation

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4450 Production of Camel Nanobodies against of Anti-Morphine-3-Glucuronide for the Development of a Biosensor for Detecting Illicit Drug

Authors: Shirin Jalili, Sadegh Hasannia, Hadi Shirzad, Afshin Khara

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Morphine is one of the most medicinally important analgesics and narcotics. Structurally, it is classified as an alkaloid because of the presence of nitrogen. Its structure is similar to that of codeine, thebaine, and heroin. An immunoassay to accurately discriminate between these analogous alkaloids would be highly beneficial. A key factor for such an assay is specificity with high sensitivity, which is totally dependent on the antibody employed. However, most antibodies against haptens are polyclonal serum antibodies that exhibit significant cross-reactivities with closely related compounds. The camel-derived single-chain antibody fragments (VHH) are the smallest molecules with antigen-binding capacity, possessing unique properties compared to other conventional antibodies. In this study, a library containing the VHH genes of a camel immunized with with morphine conjugated BSA following phage display technology was generated. By screening the camel-derived variable region of the heavy chain cDNA phage display library with the ability to bind the desired hapten, we obtained some nanobodies that recognize this hapten. Phage display expression of the Nbs from this library and pannings against this hapten resulted in a clear enrichment of four distinct Nb-displaying phages with specificity for morphine that could be a potential target site for the development of new strategies for the development of a biosensor for detecting illicit drug.

Keywords: phage display, nanobody, Morphine-3, glucuronide, ELISA, biosensor

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4449 Post Coronary Artery Stenting Reflighting: Need for Change in Policy with Changing Antiplatelet Therapy

Authors: Keshavamurthy Ganapathy Bhat, Manvinderpal Singh Marwaha

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Background: Coronary artery Disease (CAD) is a common cause of morbidity, mortality and reason for unfitness amongst aircrew. Coronary angioplasty and stenting are the standard of care for CAD. Antiplatelet drugs like Aspirin and Clopidogrel(Dual Antiplatelet therapy) are routinely prescribed post-stenting which are permitted for flying. However, in the recent past, Ticagrelor is being used in place of Clopidogrel as per ACC AHA and ESC guidelines. However Ticagrelor is not permitted for flying. Case Presentation: A 55-year-old pilot suffered Anterior Wall Myocardial Infarction. Angiography showed blockages in Left Anterior Descending Artery(LAD) and Right coronary artery (RCA). He underwent primary angioplasty and stenting LAD and subsequent stenting to RCA. Recovery was uneventful. One year later he was asymptomatic with normal Left ventricular function and no reversible perfusion defect on stress MPI. He had patent stents and coronaries on check angiogram. However, he was not allowed to fly since he was on Ticagrelor. He had to be switched over to Clopidogrel from Ticagrelor one year after stenting to permit him for flying. Similarly, switching had to be done in a 45-year-old pilot. Ticagrelor has been proven to be more effective than clopidogrel and as safe as Clopidogrel in preventing stent thrombosis. If Clopidogrel is being permitted, there is no need to restrict Ticagrelor. Hence "Policy" needs to be changed. Conclusions: Dual Antiplatelet therapy is the standard of care post coronary stenting which has been proved safe and effective. Policy needs to be changed to permit flying with Ticagrelor which is more effective than Clopidogrel and equally safe.

Keywords: antiplatelet drugs, coronary artery disease, stenting, ticagrelor

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4448 Pharmacokinetics, Dosage Regimen and in Vitro Plasma Protein Binding of Danofloxacin following Intravenous Administration in Adult Buffaloes

Authors: Zahid Manzoor, Shaukat Hussain Munawar, Zahid Iqbal, Imran Ahmad Khan, Abdul Aziz, Hafiz Muhammad Qasim

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The present study was aimed to investigate the pharmacokinetics behavior and optimal dosage regimen of danofloxacin in 8 adult healthy buffaloes of local breed (Nili Ravi) following single intravenous administration at the dose of 2.5 mg/kg body weight. Plasma drug concentrations at various time intervals were measured by HPLC method. In vitro plasma protein binding was determined employing the ultrafiltration technique. The distribution and elimination of danofloxacin was rapid, as indicated by the values (Mean±SD) of distribution half-life (t1/2α = 0.25±0.09 hours) and elimination half life (t1/2β = 3.26±0.43 hours), respectively. Volume of distribution at steady state (Vss) was 1.14±0.12 L/kg, displaying its extensive distribution into various body fluids and tissues. The high value of AUC (9.80±2.14 µg/ml.hr) reflected the vast area of the body covered by drug concentration. The mean residence time was noted to be 4.78±0.52 hours. On the basis of pharmacokinetic parameters, a suitable intravenous regimen for danofloxacin in adult buffaloes would be 6.5 mg/kg to be repeated after 12 hours intervals. The present study is the foremost pharmacokinetic study of danofloxacin in the local species which would provide the valueable contribution in the local manufacturing of danofloxacin in Pakistan in future.

Keywords: danofloxacin, pharmacokinetics, plasma protein binding, buffaloes, dosage regimen

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4447 Genotoxic Effect of Tricyclieandidepressant Drug “Clomipramine Hydrochloride’ on Somatic and Germ Cells of Male Mice

Authors: Samia A. El-Fiky, F. A. Abou-Zaid, Ibrahim M. Farag, Naira M. Efiky

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Clomipramine hydrochloride is one of the most used tricyclic antidepressant drug in Egypt. This drug contains in its chemical structure on two benzene rings. Benzene is considered to be toxic and clastogenic agent. So, the present study was designed to assess the genotoxic effect of Clomipramine hydrochloride on somatic and germ cells in mice. Three dose levels 0.195 (Low), 0.26 (Medium), and 0.65 (High) mg/kg.b.wt. were used. Seven groups of male mice were utilized in this work. The first group was employed as a control. In the remaining six groups, each of the above doses was orally administrated for two groups, one of them was treated for 5 days and the other group was given the same dose for 30 days. At the end of experiments, the animals were sacrificed for cytogenetic and sperm examination as well as histopathological investigations by using hematoxylin and eosin stains (H and E stains) and electron microscope. Concerning the sperm studies, these studies were confined to 5 days treatment with different dose levels. Moreover, the ultrastructural investigation by electron microscope was restricted to 30 days treatment with drug doses. The results of the dose dependent effect of Clomipramine showed that the treatment with three different doses induced increases of frequencies of chromosome aberrations in bone marrow and spermatocyte cells as compared to control. In addition, mitotic and meiotic activities of somatic and germ cells were declined. The treatments with medium or high doses were more effective for inducing significant increases of chromosome aberrations and significant decreases of cell divisions than treatment with low dose. The effect of high dose was more pronounced for causing such genetic deleterious in respect to effect of medium dose. Moreover, the results of the time dependent effect of Clomipramine observed that the treatment with different dose levels for 30 days led to significant increases of genetic aberrations than treatment for 5 days. Sperm examinations revealed that the treatment with Clomipramine at different dose levels caused significant increase of sperm shape abnormalities and significant decrease in sperm count as compared to control. The adverse effects on sperm shape and count were more obviousness by using the treatments with medium or high doses than those found in treatment with low dose. The group of mice treated with high dose had the highest rate of sperm shape abnormalities and the lowest proportion of sperm count as compared to mice received medium dose. In histopathological investigation, hematoxylin and eosin stains showed that, the using of low dose of Clomipramine for 5 or 30 days caused a little pathological changes in liver tissue. However, using medium and high doses for 5 or 30 days induced severe damages than that observed in mice treated with low dose. The treatment with high dose for 30 days gave the worst results of pathological changes in hepatic cells. Moreover, ultrastructure examination revealed, the mice treated with low dose of Clomipramine had little differences in liver histological architecture as compared to control group. These differences were confined to cytoplasmic inclusions. Whereas, prominent pathological changes in nuclei as well as dilated of rough Endoplasmic Reticulum (rER) were observed in mice treated with medium or high doses of Clomipramine drug. In conclusion, the present study adds evidence that treatments with medium or high doses of Clomipramine have genotoxic effects on somatic and germ cells of mice, as unwanted side effects. However, the using of low dose (especially for short time, 5 days) can be utilized as a therapeutic dose, where it caused relatively similar proportions of genetic, sperm, and histopathological changes as those found in normal control.

Keywords: clomipramine, mice, chromosome aberrations, sperm abnormalities, histopathology

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