Dissertations / Theses: 'Regulatory Affair'

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Villa, Federico. "The determinants of market access for medicines: theoretical issues and empirical evidence." Doctoral thesis, Università del Piemonte Orientale, 2021. https://hdl.handle.net/11579/148544.

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To frame the determinants of drug prices within a complex regulatory system and how these determinants influence the P&R decisions of medicine, an analysis of the Italian reference context as a whole was done, starting from the trends in the use and consumption of drugs, to the analysis of the regulatory process and market access for specific categories of drugs, orphan drugs for rare diseases. Some of the system's shortcomings are the result of limited quality control as a whole over the years, which has led to the adoption of compartmentalized pharmaceutical policies without a medium-long term strategic vision integrating clinical, pharmacoeconomic, and organizational aspects. By critically analyzing the regulatory and access system that regulates the price and reimbursement of drugs, it was possible to: (i) verify the difficult coexistence, in some cases, of European early access strategies with a rapid and complete assessment of HTA at the national level (which frustrate efforts to promote faster drug access pathways); (ii) highlight how the perception of a drug's innovativeness produces different policies in the main regulatory agencies; (iii) to underline the different view of the value of a drug between the company and the payer; (iv) the use of non-standardized P&R criteria for the definition of P&R by AIFA for different products (even for the same therapeutic area); (v) as some classes of drugs, such as orphan drugs, have had a significant increase in terms of products developed thanks to strategies to encourage investment in a previously unprofitable sector, but how this increase has also led to a significant increase in expenditure due to a P&R model not related to the low epidemiology of these diseases and/or the real impact in terms of clinical benefits of these products.

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Costa, Sara Filipa Abrantes. "Training in regulatory strategy and regulatory affairs of health products." Master's thesis, Universidade de Aveiro, 2012. http://hdl.handle.net/10773/10587.

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Mestrado em Biomedicina Farmacêutica
O presente relatório descreve as atividades desenvolvidas como estagiária no departamento de Estratégia e Assuntos Regulamentares da empresa Eurotrials, Consultores Científicos, empresa especializada na investigação clínica e consultoria científica na área da saúde. O objetivo principal desta experiência de 9 meses era um primeiro contacto com mundo do trabalho, consolidando e aprofundando os conteúdos abordados no Mestrado em Biomedicina Farmacêutica. Os Assuntos Regulamentares estão fortemente envolvidos em todo o processo de desenvolvimento do produto, desde a ideia inicial ao final do seu ciclo de vida. Tendo em conta a variedade de atividades com as quais tive oportunidade de lidar, ao longo deste relatório incluí a minha perspetiva em relação à natureza multidisciplinar que envolve a temática dos Assuntos Regulamentares.
This report describes the activities performed as a trainee in the Regulatory Strategy and Regulatory Affairs department of Eurotrials, Scientific Consultants, a company specialized in clinical research and scientific consultancy in the area of health. The main objective of this 9-month experience was the first contact with the employment world, with consolidation and deeper understanding of the contents approached in the Master in Pharmaceutical Biomedicine. Regulatory Affairs are strongly involved in the entire process of the product development, since the initial idea to the end of its life-cycle. Taking into account the variety of activities I had the opportunity to deal with, in the course of this report I included my own perspective regarding the multidisciplinary nature of Regulatory Affairs.

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Dhanraj, Keshnee. "Perceptions of the pharmaceutical industry and regulators in South Africa towards registration harmonisation in the Southern African Development Community (SADC)." University of the Western Cape, 2021. http://hdl.handle.net/11394/7956.

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Magister Pharmaceuticae - MPharm
Medicines have to be regulated in an effort to monitor their quality, safety, and efficacy. The process of medicines registration is lengthy, costly, and document-heavy. Many countries have limited expertise and resources at national medicines regulatory authorities (NMRAs) and some countries have adopted unified approaches to medicines registration legislation. Harmonised guidelines and initiatives have been adopted in South Africa and the Southern African Development Community (SADC). However, there are no studies that have identified the effects of these initiatives and guidelines on major stakeholders such as the pharmaceutical industry and regulators.

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Pinho, Bárbara Marina da Silva. "Regulatory affairs role in a multinational pharmaceutical company." Master's thesis, Universidade de Aveiro, 2014. http://hdl.handle.net/10773/12967.

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Mestrado em Biomedicina Farmacêutica
The present monograph intends to present a Regulatory Affairs department at a Multinational Pharmaceutical Company, as well as the role of the professionals working in that department. The experience which led to this monograph occurred after the conclusion of the curricular part of the Masters in Pharmaceutical Medicine, and was an opportunity to apply all the knowledge previously acquired and to develop new technical and personal skills. After the contextualisation of this document, the first chapter of this monograph introduce the Regulatory Affairs Professionals describing their principal responsibilities inside of the team. Following this, the principal activities developed by these professionals are described as well as how they interact with the different stakeholders. After framing the professional and the tasks developed, the structure of the modern Regulatory Affairs department is introduced and its impact on a Pharmaceutical Company is analysed. The following chapters promote a more personal view, showing the main activities developed during this professional experience and how the knowledge acquired prior and during it influenced the achieved results.
A presente monografia propõe apresentar um departamento de Assuntos Regulamentares de uma Empresa Multinacional Farmacêutica bem como o papel do Profissional que nele trabalha. A experiência que deu origem a esta monografia foi realizada após a conclusão da parte curricular do Mestrado em Biomedicina Farmacêutica, e foi uma oportunidade de aplicar todos os conhecimentos previamente adquiridos e de desenvolver novas competências técnicas e pessoais. Após a contextualização deste documento, o primeiro capítulo desta monografia introduz o Profissional de Assuntos Regulamentares, descrevendo as suas principais atividades dentro da equipa. De seguida, apresentam-se as atividades desenvolvidas por estes profissionais descrevendo-se como interagem com as diferentes partes envolvidas. Após o enquadramento do profissional e das atividades desempenhadas, introduz-se a estrutura de um departamento de Assuntos Regulamentares moderno e analisa-se o seu impacto numa empresa farmacêutica. Os seguintes capítulos promovem uma visão mais pessoal, mostrando as principais atividades desenvolvidas durante esta experiência e como os conhecimentos adquiridos antes e durante a mesma influenciaram os resultados adquiridos.

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Pinela, Raquel Alexandra Pires. "9 months experience as a trainee regulatory affairs officer." Master's thesis, Universidade de Aveiro, 2012. http://hdl.handle.net/10773/10900.

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Mestrado em Biomedicina Farmacêutica
O presente relatório tem como objetivo descrever as atividades desenvolvidas no âmbito do estágio curricular na área dos assuntos regulamentares, que decorreu entre 1 de Agosto de 2011 e 4 de Maio de 2012, no Departamento de Manutenção do Mercado da Phagecon – Serviços e Consultoria Farmacêutica, Lda.. Este estágio é parte integrante do programa de formação do mestrado em Biomedicina Farmacêutica e teve como principais objetivos a aquisição de experiência na realização das atividades comumente associadas aos assuntos regulamentares, bem como a consolidação de conhecimentos e o desenvolvimento de novas competências técnicas. O primeiro capítulo introduz o estágio curricular em assuntos regulamentares, seguindo-se uma descrição generalista do contexto regulamentar aplicável às atividades realizadas. Os capítulos e secções posteriores destinam-se a descrever a empresa que proporcionou o estágio, os objetivos para este definidos e as atividades e tarefas desempenhadas. Por último, será feita uma discussão crítica do estágio, incluído a análise das principais dificuldades sentidas e as competências adquiridas.
This report aims to describe the activities performed during the curricular internship in regulatory affairs, which took place from August 1, 2011 to May 4, 2012 at Marketing Maintenance Department of Phagecon – Serviços e Consultoria Farmacêutica, Lda.. The internship is an essential part of the training programme in Pharmaceutical Biomedicine and it main goals were: to gain experience in conducting common regulatory activities; to consolidate background knowledge and to develop new technical skills. The first chapter introduces the internship and is followed by a general description of the regulatory environment applicable to the activities performed. The later chapters and respective sections intend to: describe the hosting company, define internship goals and give a detailed description of the activities and tasks performed during this 9 months experience. Finally, it will be presented a critical discussion of internship outcomes, including the analysis of the main difficulties and key competences acquired.

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Mukoma, Collins. "Exploration of the Training/Educational Background and The Roles of Regulatory Affairs Associates/Officers in selected South African Based Pharmaceutical Companies in Gauteng Province." University of the Western Cape, 2004. http://hdl.handle.net/11394/8235.

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>Magister Scientiae - MSc
Regulatory Affairs (RA), within the pharmaceutical business, could be a profession that covers completely different registration parameters of a pharmaceutical product. This is often a replacement profession that was developed to shield public health by providing the smart quality pharmaceutical product as well as safety and efficacy. The study aimed to explore the coaching and role of RA associates/officers in pharmaceutical corporations in Gauteng, South Africa. The study was a cross-sectional survey, which utilized google forms with both open and closed-ended questions. Using descriptive statistics, it was found that, majority of the participants (78.3%) (RA assistants, officers, and scientists) indicated that most of the responsibilities they carry out were through informal training (i.e. learning on the job). However, even though various pharmaceutical companies have different titles for this personnel, it was observed that most of them perform almost the same functions (i.e. Prepare submissions of license variations and renewals to strict deadlines, with 91.3% of the participants learning the skills on the job). Furthermore, it was recorded that most RA personnel have experience of between 1-5 years (56.6 %) and that most RA personnel acquired their job through an internship (43.5%) and external vacancy (43.5%). Moreover, it was also observed that most RA personnel (43.5%) have more than one qualification (Honours Degree and MSc Degree). Although specialized training is required for RA personnel, only 30.4% of the participants were trained to provide strategic advice to senior management throughout the development of a new product. About 13.0% of the participants were trained to plan and develop product trials and interpret trial data.

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Kachirskaia, Ioulia. "Identifying a potential substrate of Plasmodium Falciparum cell cycle regulatory Kinase PFPK5." Honors in the Major Thesis, University of Central Florida, 2003. http://digital.library.ucf.edu/cdm/ref/collection/ETH/id/321.

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This item is only available in print in the UCF Libraries. If this is your Honors Thesis, you can help us make it available online for use by researchers around the world by following the instructions on the distribution consent form at http://library.ucf.edu/Systems/DigitalInitiatives/DigitalCollections/InternetDistributionConsentAgreementForm.pdf You may also contact the project coordinator, Kerri Bottorff, at kerri.bottorff@ucf.edu for more information.
Bachelors
Health and Public Affairs
Molecular Biology and Microbiology

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Bodnar, Olivia Verfasser], and Justus [Gutachter] [Haucap. "Five Empirical Essays on Antitrust and Regulatory Affairs / Olivia Bodnar ; Gutachter: Justus Haucap." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2021. http://d-nb.info/1224679326/34.

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Williams, George. "Establishing an effective economic regulatory policy for the European airline industry." Thesis, Cranfield University, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.278751.

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Gooch, Rebecca L. "Television production, regulation and enforcement reasons for broadcasters' non-compliance and a weakened state of regulatory affairs." Thesis, London School of Economics and Political Science (University of London), 2012. http://etheses.lse.ac.uk/353/.

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This thesis examines a group of television-makers that aimed to circumvent the regulations affecting standards of content and to reshape the boundaries of permissible violent content. It also examines the regulators who, in a period of significant regulatory restructuring, were required to police those boundaries and protect viewers from ‘harmful’ or ‘offensive’ content, and programme-contributors from ‘unfair’ treatment. In doing so, the aim is to offer a broader, empirically rich understanding of the individual, organisational and external factors that can lead to non-compliance and the relaxation of regulatory affairs over time; and to understand how rules or regulations can get pushed and reshaped. My findings revealed that both regulators and television-makers were confronted by conflicting economic and public interest objectives/responsibilities, and that, due to a variety of individual, organisational and external-level factors, they tended to prioritise their economic obligations, and this led to a loosening of the standards of consumer protection. The factors that influenced television-makers’ and regulators’ decision-making, and thereby this sequence of events, included, but were not limited to, the government’s shift toward deregulation, technological advancements, changing politics, a competitive organisational culture and a lack of sufficient accountability for television-makers.

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Maloney, William A. "The politics and dynamics of organisational and regulatory change in the water industry in England and Wales 1945-1993." Thesis, University of Strathclyde, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.389973.

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Laaroubi, Khalid. "Étude biochimique et moléculaire du facteur de croissance heparin affin regulatory peptide (HARP)." Paris 12, 1995. http://www.theses.fr/1995PA120013.

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Depuis plusieurs annees, notre laboratoire s'interesse aux facteurs de croissance ayant une affinite pour l'heparine. Notre experience dans ce domaine, ainsi que la disponibilite tres recente de differentes techniques d'analyses, nous a amenes a la detection puis a la purification a partir d'extraits de cerveau de buf adulte, d'une nouvelle molecule de 18 kda nommee harp. Nous avons decrit harp comme un facteur de croissance ayant des activites mitogene et neurotrophe. Son activite mitogene a par la suite ete remise en question par certains groupes qui, pour des raisons inconnues n'ont pu la mettre en evidence. Ils pretendaient, sans pourtant le demontrer, que l'activite mitogene de l'harp pourrait etre due a une contamination par du fgf ou par d'autres molecules ayant des proprietes identiques. Dans le but de lever cette controverse, nous avons clone l'adn complementaire de l'harp et apres transfection de cet adn dans des cellules nih 3t3, nous avons etudie les proprietes biologiques de la molecule recombinante ainsi produite. Nous avons montre que la proteine harp recombinante stimulait un grand nombre de cellules, notamment les cellules epitheliales et endotheliales et que cette activite mitogene est modulee par l'heparine. De plus, nous avons etabli dans un modele in vitro le role preponderant de l'harp dans les mecanismes participant a l'angiogenese. L'etablissement de la sequence peptidique de la proteine recombinante biologiquement active a revele l'existence d'une nouvelle forme d'harp, possedant trois acides amines supplementaires du cote n-terminal par rapport a la forme initialement decrite. Cette nouvelle forme moleculaire a ete recemment isolee a partir de surnageant d'une culture primaire de cellules epitheliales de cristallin de buf. Concernant l'implication physiologique et physiopathologique de l'harp, deux etudes ont ete menees au niveau de la prostate et du placenta

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Mrazek, Monique Francine. "The impact of differing regulatory frameworks on post-patent pharmaceutical markets in the United Kingdom, United States and Germany 1990 to 1997." Thesis, London School of Economics and Political Science (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.391052.

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This thesis analysed the effects of different regulatory frameworks on the post-patent pharmaceutical markets of the United Kingdom, Germany and the United States between 1990 and 1997. Firstly, an extensive search of peer reviewed and 'grey' literature was undertaken to develop an understanding of both the pharmaceutical and wider health policy environments during the period of study. Preference was given to prospective before and after studies with and without control groups, retrospective studies with and without controls, and case studies that were reinforced by similar supporting case studies. A comparative policy analysis of the regulatory frameworks of the three countries linked the actual or expected outcomes to pharmaceutical policies promoting the demand and supply of generic drugs. Secondly, this thesis analysed the effects of the different regulatory frameworks the cost of off-patent medicines. Molecules were selected for the study if they had experienced patent expiration between 1990 and 1997, as well as having experienced entry by two or more generic equivalents over the same time period. Contingency tables were calculated for each pair of variables analysed. The associations between the variables were tested by chi-square and the strength of the relationships was measured by Ganmia. Trends in the pricing and volume of the branded original and generic equivalents were compared. A statistical model was developed as a framework to determine significant factors affecting the market share of the original branded drug after patent expiration. The statistical model was estimated both by ordinary least squares regression and by a fixed-effects estimation. Finally, conclusions were drawn from the comparative analysis of these different regulatory approaches and policy implications are discussed.

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Augusto, Ana Isabel Santos. "Curricular internship in a clinical pharmacology unit." Master's thesis, Universidade de Aveiro, 2015. http://hdl.handle.net/10773/14882.

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Mestrado em Biomedicina Farmacêutica
The present internship report is a detailed description of my experience in the curricular internship performed at the Clinical Pharmacology Unit of the Instituto de Medicina Molecular, from October 13th 2014 to June 5th 2015. This internship was performed as part of the second and final year of the Master’s Degree in Pharmaceutical Biomedicine of the University of Aveiro. During the course of the experience I had the opportunity to participate in several projects in collaboration with different teams, most relevantly the activities related to the regulatory submission of a clinical trial in Portugal and related to the training in Pharmacovigilance. This internship has allowed me to put into practice the knowledge acquired during my academic training and deepen my knowledge on Clinical Research in a practical perspective. Additionally, it has also allowed me to improve many of skills and to understand my interests, capacities, weaknesses and strengths. In conclusion, I can affirm that this internship was an outstanding training and a very valuable professional and personal experience, for the main established objectives were achieved and exceeded.
O presente relatório de estágio descreve detalhadamente a minha experiência no estágio curricular realizado na Unidade de Farmacologia Clínica do Instituto de Medicina Molecular, desde 13 de Outubro de 2014 até 5 de Junho de 2015. Este estágio foi realizado como parte do segundo ano do Mestrado em Biomedicina Farmacêutica da Universidade de Aveiro. Durante o decorrer desta experiência, tive a oportunidade de participar em diversos projetos em colaboração com diferentes equipas, destacando-se as atividades relacionadas com a submissão de um ensaio clínico em Portugal e as atividades no âmbito da formação em Farmacovigilância. Este estágio possibilitou-me pôr em prática os conhecimentos obtidos durante a minha formação académica e aprofundar o meu conhecimento sobre investigação clínica, numa perspetiva prática. Para além disso, permitiu-me melhorar as minhas competências e perceber os meus interesses, capacidades, pontos fracos e fortes. Concluindo, posso afirmar que este estágio foi uma aprendizagem excelente e uma experiência de grande valor a nível profissional e pessoal, tendo conseguido atingir e ultrapassar os principais objetivos estabelecidos.

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Jacobs, Debra. "Do State Regulatory Institutions Matter: Using Network Theory to Explore Linkages between Air Policy Boards and Pollution Outcomes." VCU Scholars Compass, 2009. http://scholarscompass.vcu.edu/etd/2040.

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The purpose of this study is to test an adapted model of network theory against state air pollution control institutions. Air pollution control presents a regulatory problem that has interstate, intrastate and multiple federal dimensions. It is one of extreme complexity and uncertainty, from both a regulatory and scientific perspective. The changing political environment federally has enabled states to redefine their roles in the regulatory process (Adler, 1997; Krane, 2007). Drawing from network theory in intergovernmental policy processes my research tests three key factors in explaining state air pollution levels: tenure in office of the air policy administrator, the use of air policy boards, and networking encompassing agency heads, air boards and the public. Theoretically this research builds upon important work by William Berry, Paul Teske, Lawrence O’Toole, Kenneth Meier and Mark Schneider in empirically investigating the network theory of policy behavior. Network theory, as envisioned by O’Toole and Meier, provides for systematic empirical research on intergovernmental management. This research expands the network model to incorporate citizen participation and information access in agency policy-making. Further, this research develops the ozone exposure index as the dependent measure and metric of agency performance. The study limits itself to the time frame of 1999-2007. This time-frame enables me to pool data on the instances of nonattainment of National Air Quality standards for ground-level ozone. This study limits itself to ground-level ozone as the dependent measure. Ground-level ozone is primarily regulated at the state level. It and PM2.5 represent the greatest threats to human health nationally. A series of panel data statistical models are tested revealing that the two-way generalized least squares random effects regression proves the best fit for the data. Results support the hypothesis that the tenure of the air administrator positively impacts pollution reduction. The number of citizen members on air policy boards is also found positively correlated to pollution reduction. This research contributes to the field by expanding the reach of the network model to air policy. It also incorporates citizen participation into the model. Lastly, it also posits that institutional structure can be successfully tied to performance.

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Rehnström, Ida. "MedTech Firms' Business Model Alignment with Healthcare Institutional Logic : Successful Commercialization." Thesis, Luleå tekniska universitet, Institutionen för ekonomi, teknik och samhälle, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:ltu:diva-85334.

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MedTech firms experience barriers when entering the healthcare sector, although their solutions could solve healthcare challenges. The study provides a conceptual framework for MedTech firms' business environment including institutional alignments and misalignments. These insights support MedTech firms' business model development when aiming for successful commercialization. The research is conducted with a multiple case study analyzing MedTech firms' and healthcare organizations' perspective regarding the business environment and relationship dynamics. The study generated three main findings. Firstly, an organizational and institutional logic analysis outlined essential problem areas where MedTech firms and healthcare organizations align differently. Secondly, suggestions on how the MedTech firm can respond to the identified problem areas through their business model are presented. Thirdly, the study provides an example of how social- and business literature can be connected to understand complex business environments. In contrast to a majority of prior research, the study is designed for the MedTech firm's perspective where the final result answering how the business model can be improved based on healthcare organizational and business insights.

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Bernard-Pierrot, Isabelle. "Mise en évidence de déterminants structuraux impliqués dans les activité biologiques du facteur de croissance HARP (Heparin affin regulatory peptide)." Paris 11, 2002. http://www.theses.fr/2002PA11T027.

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L'HARP (Beparin Affin Regulatory Peptide) est un facteur de croissance de 18 kDa, se liant à l'héparine, fortement exprimé dans les tumeurs primaires humaines d'origine mammaire, gastro-intestinale et prostatique. L'HARP est considéré comme un facteur angiogène favorisant la progression tumorale et la dissémination métastasique. Son implication dans le processus tumoral est liée à ses activités mitogène, angiogène et transformante. L'HARP induit également, in vitro, la croissance neuritique de neurones embryonnaires de rat. Nos travaux, visant à corréler la structure de la protéine avec ses activités biologiques, montrent que l'HARP est capable de former des dimères non covalents en présence d'héparine ou de glycosaminoglycanes et suggèrent que cette forme dimérique est responsable des activités mitogène, angiogène et transformante de la protéine. Nous avons, par ailleurs, mis en évidence l'importance des résidus C-terminaux 111-136 de l'HARP dans le maintien de ces trois activités, alors qu'ils ne sont pas impliqués dans l'activité neurotrope de la protéine. Cette activité semble être exercée par les deux domaines en feuillet de la molécule, contenant chacun un motif de type TSR-1. Nos travaux démontrent également que l'HARP tronqué de ses 25 derniers acides aminés côté C-terminal (HΔ111-136), inhibe les activités mitogène, angiogène et transformante de l'HARP sauvage via une hétérodimérisation avec cette molécule. Le peptide synthétique P111-136 correspondant à cette délétion présente in vitro les mêmes propriétés inhibitrices vis à vis de l'HARP sauvage. Cependant, dans ce cas, l'inhibition est réalisée par compétition avec la protéine HARP au niveau de son site de fixation sur le récepteur cellulaire de haute affinité ALK (Anaplastie Lymphoma Kinase)
Heparin-binding Growth-associated Molecule (HB-GAM) is a heparin-binding molecule involved in neurite outgrowth and is closely related the mammalian produced growth factors Pleiotrophin or HARP reported to stimulate proliferation of several cell types including endothelials. Here, we report that HB-GAM inhibited the biological activity induced by the 165-amino acid form ofvascular endothelial growth factor (VEGF165) on human umbilical vein endothelial cells (HUVEC). Endothelial-cell proliferation induced by VEGFI65 showed about 50% inhibition in the presence of HB-GAM in a concentration of 2. 7 nM (ICso). In similar concentrations, HB-GAM blocked HUVEC migration and tube formation induced by VEGF165 in three-dimensional angiogenesis assays. In addition, HB-GAM inhibited binding of 125I-VEGF l65 to the VEGF receptors of HUVEC (IC50 : 35 nM). Additional studies using heparan sulfate deficient CHO cells that overexpressed VEGF receptors indicated that binding of 125I-VEGF165 to fms-like tyrosine kinase-1 receptor, kinase insert domaincontaining receptor and neuropilin receptor was inhibited by HB-GAM with an IC50 in the nanomolar range. We then investigated the mechanisms of this inhibition. Using a solid-phase ligand-binding assay, we found that HB-GAM interacted directely with VEGF165, with a dissociation coefficient of 1. 38 nM. Further studies indicated that the two HB-GAM -sheet domains containing the thrombospondin type-1 repeats were involved in this interaction

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Héroult, Mélanie. "Etude de la modélisation de l'angiogénèse par le facteur de croissance "Heparin Affin Regulatory Peptide" : implication dans les pathologies arthritiques." Paris 12, 2002. http://www.theses.fr/2002PA120002.

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L'angiogenèse est un processus dynamique par lequel de nouveaux capillaires sanguins sont formés par excroissance de vaisseaux pré-existants et qui est associé au développement de nombreuses pathologies prolifératives. Le but de cette étude a é d'identifier les différents domaines structuraux du facteur de croissance Heparin Affin Regulatory peptide (HARP) impliqués dans 1' angiogenèse et de rechercher la présence d'HARP dans certaines pathologies rhumatismales où le processus angiogène est déterminant. Dans cette étude, nous avons mis en évidence que I'HARP et des peptides correspondants aux extrémités N- et C-terminales de la molécule induisent selon le type de cellules endothéliales, des effets différents sur la prolifération, la migration et la différenciation. Sur les cellules endothéliales de veine ombilicale humaine, nous avons étudié le mécanisme d'action inhibiteur de l'HARP sur l'activité angiogène du VEGFI L'HARP se lie au VEGF et inhibe la fixation du VEGFI à ses récepteurs. Une étude portant sur les relations structure- fonction de l'HARP a mis en évidence que la séquence d'interaction met en jeu les domaines comportant des motifs d'homologie de type 1 de la thrombospondine-1 (TSR1) présents dans l'HARP. Parallèlement, nous avons étudié le rôle de I'HARP dans les pathologies arthritiques. L'HARP est surexprimé dans les liquides synoviaux et les membranes synoviales de patients atteints de pathologies arthritiques. Les résultats sur la distribution de ce facteur et différentes études in vitro sur le mécanisme d'action de l'HARP sur les synoviocytes, nous ont conduits à formuler l'hypothèse que l'HARP serait un facteur de croissance impliqué dans l'angiogenèse associée aux arthrites chroniques.

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Andam, Kwaw Senyi. "Essays on the Evaluation of Land Use Policy: The Effects of Regulatory Protection on Land Use and Social Welfare." Digital Archive @ GSU, 2007. http://digitalarchive.gsu.edu/pmap_diss/20.

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Societies frequently implement land use policies to regulate resource extraction or to regulate development. However, two important policy questions remain unresolved. First, how effective are land use regulations? Second, how do land use regulations affect socioeconomic conditions? Three issues complicate the evaluation of land use policies: (1) overt bias may lead to incorrect estimates of policy effects if implementation is nonrandom; (2) the policy may affect outcomes in neighboring unregulated lands; and (3) unobservable differences between regulated and unregulated lands may lead to biased assessments. Previous evaluations of land use policies fail to address these sources of bias simultaneously. In this dissertation, I develop an approach, using matching methods, which jointly accounts for these complications. I apply the approach to evaluate the effects of Costa Rica s protected areas on land use and socioeconomic outcomes between 1960 and 2000. I find that: (1) protection prevented the deforestation of only 10 percent or less of protected forests; (2) protection resulted in reforestation of only 20 percent of non-forest areas that were protected; (3) protection had little effect on land use outside protected areas, most likely because, as noted above, protected areas had only small effects on land use inside protected areas; and (4) there is little evidence that protected areas had harmful impacts on the livelihoods of local communities: on the contrary, I find that protection had small positive effects on socioeconomic outcomes. Furthermore, the methods traditionally used to conduct such evaluations are biased. In contrast to the findings above, those conventional methods overestimated the amount of avoided deforestation and erroneously implied that protection had negative impacts on the livelihoods of local communities. This dissertation contributes to policymaking by providing empirical measures of protected area effectiveness. Although annual global expenditures on protected areas are about $6.5 billion, little is known to date about the returns on these investments. This study also indicates that policymakers should give careful consideration to current proposals to compensate communities living in or around protected areas: contrary to widely held assumptions, the findings suggest that protection may not have harmful effects on socioeconomic outcomes.

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Bouderlique, Thibault. "Etude des propriétés ostéoinductrices et chondroinductrices de "l'Heparin affin regulatory peptide" sur les cellules stromales mésenchymateuses humaines, application en régénération osseuse." Phd thesis, Université Paris-Est, 2012. http://tel.archives-ouvertes.fr/tel-00904131.

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La régénération osseuse est un processus impliquant de nombreux types cellulaires comme les ostéoblastes, les chondrocytes ou les cellules stromales mésenchymateuses (CSM). Les CSM possèdent des capacités de différenciation suggérant leur implication dans ce processus de réparation. La régénération osseuse est le fruit de la coordination complexe de l'activité de nombreux facteurs de croissance. Parmi eux, l'" Heparin affin regulatory peptide " (HARP) est fortement exprimé dans le callus durant la régénération mais son rôle n'est pas clairement établi. Le but de ce travail de thèse a été (1) d'évaluer les effets de HARP sur les propriétés de migration, de prolifération et de différenciation des CSM in vitro ; (2) évaluer la capacité de HARP à induire une formation osseuse ou une régénération osseuse in vivo.Nos résultats démontrent que HARP est chémoattractant pour les CSM et potentialise leur prolifération. De plus, nous montrons pour la première fois que le traitement de CSM par HARP durant leur chondroinduction conduit à une différenciation chondrocytaire de type hypertrophique. Ce type cellulaire est primordial dans les derniers stades de la formation osseuse endochondrale qui se met en place durant la croissance osseuse, mais également durant la réparation. L'implantation de biomatériaux associés à HARP dans un défaut osseux de condyle fémoral a conduit à la formation de cartilage et d'os dans l'implant, reproduisant le mécanisme physiologique de formation osseuse endochondrale. Le biomatériau seul n'a été envahi que par du tissu fibreux.Durant les processus de réparation tissulaire, les glycosaminoglycannes (GAG), des chaînes polysaccharidiques sulfatées, composants majeurs de la matrice extracellulaire, participent à la modulation des effets des facteurs de croissance durant la réparation. Récemment, des mimétiques structuraux et fonctionnels des GAG ont été développés. Durant ma thèse, j'ai été associé au travail d'un doctorant de l'équipe de P.Albanese, qui a montré que des mimétiques de GAG induisent une différenciation ostéoblastique des CSM en l'absence de traitement ostéoinducteur. L'implantation sous-cutanée de biomatériaux covalemment associés aux mimétiques ont également été menées, et ont permis d'observer des potentialisations des processus de vascularisation de l'implant et de l'activité ostéoclastique. Ces resultats ont permis de valider l'interêt des GAG mimétiques dans le cadre des thérapies de régénération osseuse.Cette étude démontre pour la première fois les effets chondroinducteurs directs de HARP sur la production de molécules de la matrice cartilagineuse par les CSM in vitro, mais également sur la synthèse de tissu cartilagineux in vivo. Les effets de HARP observés sur la régénération osseuse confirment qu'il pourrait être un bon candidat en chirurgie orthopédique en permettant une régénération de type endochondrale typique de la réparation physiologique. De plus les nouvelles stratégies developpées dans le laboratoire sur la fonctionnalisation covalente de biomateriaux par des GAG mimétiques, meriteraient d'etre testées en association avec HARP, afin d'augmenter sa demi-vie et de controler son relarguage et ses activités biologiques in vivo.

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Zhang, Lei. "Uncompensated Care Provision and the Economic Behavior of Hospitals: the Influence of the Regulatory Environment." Diss., unrestricted, 2008. http://etd.gsu.edu/theses/available/etd-02242009-152847/.

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Thesis (Ph. D.)--Georgia State University, 2008.
Title from file title page. Paul G. Farnham, committee chair; Patricia G. Ketsche , Douglas S. Noonan (Ga. Tech.), Shiferaw Gurmu, Karen J. Minyard, William S. Custer, committee members. Description based on contents viewed June 11, 2009. Includes bibliographical references (p. 146-153).

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Elahouel, Rania. "Le Fibroblast Growth Factor 2 ( FGF-2 ) et la neuropiline-1 (NRP-1) : nouveaux partenaires moléculaires de Heparin Affin Regulatory Peptide ( HARP)." Thesis, Paris Est, 2012. http://www.theses.fr/2012PEST0066.

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HARP (Heparin Affin regulatory peptide) est un facteur de croissance qui constitue avec la midkine une sous-famille des Heparin Binding Growth Factors (HBGFs). HARP est impliqué dans de nombreux processus physiologiques comme la neurogenèse et la vasculogenèse mais aussi dans des processus physiopathologiques comme l’angiogenèse et la progression tumorale. HARP interagit avec différents récepteurs (N-syndécan, RPTPβ/ζ, et ALK). Plus récemment, il a été montré au laboratoire que la nucléoline, protéine navette entre le noyau, le cytoplasme, et la surface cellulaire est un nouveau récepteur à HARP. Malgré les avancées dans ce domaine, l’interaction de HARP avec ses récepteurs n’est pas totalement élucidée. L'objectif de ce projet de thèse était la recherche de nouveaux partenaires moléculaires qui interagissent avec HARP, de comprendre le mécanisme de leurs interaction et d’analyser les effets biologiques. A ce titre, j’ai participé à l’étude de l’interaction de HARP avec le facteur de croissance des fibroblastes, le FGF-2. Ce facteur liant l’héparine est également mitogène et angiogène. En utilisant des techniques de biocapteurs optiques et d’interaction protéine-protéine, nous avons montré une interaction directe entre HARP et le FGF-2 et qui implique les domaines C-TSR-I et C-terminale de HARP. De plus, cette interaction inhibe la migration et la prolifération des cellules endothéliales, induites par le FGF-2 ou par HARP seuls. En parallèle, j’ai mis en évidence l’interaction entre HARP et la NRP-1. NRP-1 est une protéine transmembranaire, ayant comme ligands principaux, les sémaphorines de classe 3 (SEMA 3A), le facteur de croissance endothélial vasculaire (VEGF) et le FGF-2. En plus de son rôle crucial dans le développement des systèmes nerveux et cardiovasculaires, la NRP-1 est impliquée dans les processus physiopathologiques tels que l’angiogenèse et l’invasion tumorale. Ainsi, la NRP-1 présente un profil biologique similaire à HARP. En utilisant des tests d’ELISA, d’immunoprécipitation et de « pull-down », nous avons montré que HARP interagit avec la NRP-1. Cette interaction semble être directe et s’effectue via les domaines de liaison à l’héparine TSR-I. HARP induit l’internalisation de la NRP-1 au bout de 15 minutes et son recyclage partiel à la surface cellulaire au bout d’une heure. L’internalisation de la NRP-1 s’accompagne par la phosphorylation des voies MAPK (ERK1/2), Akt et FAK. L’interaction HARP/NRP-1 est cruciale pour la migration des cellules endothéliales et l’invasion des cellules tumorales. En conclusion, ces résultats apportent de nouvelles avancées concernant les partenaires moléculaires de HARP en particulier et montrent également la complexité des interactions des facteurs de croissance entre eux et avec leurs récepteurs. Plus généralement, cette étude permet d'envisager des stratégies thérapeutiques ciblant l’interaction de la NRP-1 avec HARP et aussi les autres facteurs de croissance
HARP (Heparin Affin regulatory peptide) is a growth factor that constitutes with midkine a subfamily of Heparin Binding Growth Factors (HBGFs). HARP is involved in many physiological processes such as neurogenesis and vasculogenesis but also in pathophysiological processes such as angiogenesis and tumor progression. HARP interacts with different receptors (N-syndecan, RPTPβ / ζ and ALK). More recently, it has been shown in the laboratory that nucleolin, a protein shuttle between the nucleus, cytoplasm, and cell surface, is a new HARP receptor. Despite the advances in this field, the interaction of HARP with its receptors is not fully understood. The aim of this thesis was the search for new molecular partners that interact with HARP, to understand the mechanism of their interaction and analyze the biological effects. My work was firstly to participate to the study of the interaction of HARP with the fibroblast growth factor-2, FGF-2. This factor is also an heparin-binding factor, with mitogenic and angiogenic activities. Using techniques of optical biosensors and protein-protein interaction, we have shown a direct interaction between HARP and FGF-2 that involves C-TSR-I and C-terminus domains of HARP. In addition, HARP inhibits the migration and proliferation of endothelial cells induced by FGF-2. In parallel, I highlighted the interaction between HARP and NRP-1. NRP-1 is a transmembrane protein having as main ligands, semaphorins class 3 (SEMA 3A), the vascular endothelial growth factor (VEGF) and FGF-2. In addition to its crucial role in the development of the nervous and cardiovascular systems, the NRP-1 is involved in physiopathological processes such as angiogenesis and tumor invasion. Thus, NRP-1 has a biological profile similar to HARP. Using ELISA, immunoprecipitation and "pull-down" tests, we have shown that HARP interacts with NRP-1. This interaction appears to be direct and occurs via heparin binding domains of HARP: TSR-I. HARP induces internalization of NRP-1 after 15 minutes and partial recycling to the cell surface after one hour. The internalization of the NRP-1 is accompanied by the phosphorylation of MAPK pathways (ERK1 / 2), Akt and FAK. HARP/NRP-1 interaction is crucial for endothelial cell migration and invasion of tumor cells. In conclusion, these results provide new advances on molecular partners of HARP in particular and also show the complexity of the interactions between these growth factors and their receptors. More generally, this study allows considering therapeutic strategies targeting the interaction of NRP-1 with HARP as well as other growth factors

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Dreker, David, and Jacqueline Lampey. "Policy Instruments and their Impact on Business Practice in the Fashion Industry towards Sustainability : Learning Outcomes from the Food Industry." Thesis, Högskolan i Borås, Akademin för textil, teknik och ekonomi, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:hb:diva-22107.

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The fashion industry is not only known for its creativity and innovation, but also for its contribution to environmental pollution, climate change as well as for social imbalances and poverty. Ecological and societal standards have so far only played a minor role in this industry for production and distribution as well as for consumers for their consumption and disposal behaviour. However, in order to achieve the UN Sustainable Development Goals and prevent the maximum damage caused by pollution and exploitation, it is necessary to act more rapidly and consistently. Governmental control instruments can help to address those responsible, to regulate the market and to encourage improvements towards a more sustainable economy. The aim of this work is to develop a feasible governmental control instrument for the textile sector in order to provide possible solutions for some of the existing problems. Three different cases of already implemented policies in the food sector will be analysed and evaluated in order to detect the best-case policy with regard to sustainability as a basis for a derivation. The findings of the derived outcome will then be examined by experts in order to validate it. Finally, a recommendation summarises the findings of the literature review, the transfer of knowledge as well as the expert assessments. The result of this research paper is a control instrument derived from the food industry, which was evaluated with the help of expert interviews and has the potential to make the textile market more sustainable in the long term.

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Bellan, Natália. "Diretrizes para o processo de registro sanitário dos medicamentos." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/9/9139/tde-30072015-100420/.

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O controle sanitário no Brasil merece elevado nível de consideração, pois caracteriza-se por grande importância social e econômica. Abrange um leque grande de produtos e serviços de diversas naturezas, como: medicamentos, alimentos, produtos biológicos, vacinas, hemoderivados, saneantes e desinfetantes, produtos de higiene pessoal, perfumes e cosméticos, controle dos portos, aeroportos, estações de fronteiras e uma ampla variedade de serviços à saúde. A Agência Nacional de Vigilância Sanitária (ANVISA) foi criada no Brasil especificamente conforme artigo 3º da Lei nº 9782/1999, sendo relativamente recente comparando-se com as agências regulatórias no âmbito internacional, e desde então evoluiu, angariando respeito no nível nacional e internacional. Outras agências reguladoras igualmente importantes abrangem variedades de produtos e serviços semelhantes à ANVISA. Inclusive a Food and Drug Administration - (FDA) e a European Medicines Agency (EMA) apresentam em seu \"rool\" de medicamentos os veterinários, enquanto que no Brasil este tipo de produto é regulamentado pelo Ministério de Agricultura, Pecuária e Abastecimento (MAPA). O processo de registro no sistema de vigilância sanitária é um recurso de grande valia para assegurar a comercialização de produtos seguros e eficazes disponíveis à sociedade. Qualquer falha na cadeia produtiva pode impactar nos critérios de qualidade. Assim, a regulamentação sanitária sobre medicamentos abrange toda a cadeia farmacêutica desde o início dos estudos de pesquisa clínica até normas referente à publicidade. O objetivo desse trabalho é contribuir na promoção do conhecimento de regulação sanitária para os medicamentos pelo estudo da estrutura organizacional e atribuições da ANVISA, e paralelamente, efetuar a análise e comparação da regulamentação sanitária entre as diferentes categorias de medicamentos, bem como discutir a estratégia regulatória adotada pelo setor farmacêutico. Como material dessa pesquisa, empregou-se essencialmente, a regulamentação sanitária farmacêutica nacional, tendo como contrapontos a situação política e econômica do país, pautando-se como método a pesquisa qualitativa utilizando-se do modelo documental. Com vistas à estrutura organizacional das agências reguladoras de medicamentos descritas neste trabalho, verificou-se semelhanças inerentes as concepções técnicas e regulatórias, diferenciando-se, principalmente, da brasileira pelo fato dos medicamentos de uso humano e veterinário não estarem contemplados sob a responsabilidade da mesma instituição. Dentre as sete categorias de medicamentos estudadas, a composição técnica de seus dossiês de registro são consideravelmente análogas, sendo distintas as exigências regulatórias tangíveis aos quesitos específicos inerentes a cada tipo de medicamento. No período analisado (2009 a 2010), com o intuito de retratar a tendência regulatória adotada pelo setor farmacêutico brasileiro, as categorias de medicamentos genéricos e similares são as que mais apresentaram solicitações e deferimentos de registros no país.
The sanitary control in Brazil deserves a high level of consideration, because it is characterized by large social and economic importance. It encompasses a wide variety of products and services of various natures, as medicines, food, biological products, vaccines, blood products, sanitizing and disinfectants, toiletries, perfumes and cosmetics, control of ports, airports, frontiers stations and an extensive variety of health services. The National Agency for Sanitary Surveillance (ANVISA) was created in Brazil specifically as Article 3 of Law No. 9782/1999 and is relatively recent compared with regulatory agencies internationally, and has since evolved, gaining respect in the national and international level . Other regulatory agencies equally encompass important varieties of products and services similar from ANVISA. Even the Food and Drug Administration - (FDA) and European Medicines Agency (EMA) in its present \"rool\" medicine veterinarians, while in Brazil this type of product is regulated by the Ministry of Agriculture, Livestock and Supply (MAPA). The registration process in health monitoring system is a very valuable resource to ensure that commercialization of safe and effective products available to society. Any failure in the supply chain can impact on the quality criteria. Thus, the sanitary regulation on medicines covers the entire pharmaceutical chain since the early clinical research studies relating to the advertising standards. The objective of this work is to contribute in promoting knowledge of sanitary regulation for medicines by studying the organizational structure and responsibilities of ANVISA, and in parallel, perform analysis and comparison of the sanitary regulation between different categories of medicines, as well as discuss the regulatory strategy adopted by the pharmaceutical industry. As material of this research, we used essentially the national pharmaceutical the sanitary regulation, having as counterpoints the political and economic situation of the country, basing itself as a qualitative research method using the model document. With views to the organizational structure of drug regulatory agencies described in this study, it was found similarities inherent in the concepts and techniques regulatory, differentiating itself mainly by the fact that the Brazilian medicines for human and veterinary use are not covered under the responsibility of the same institution. Among the seven categories of drugs studied, the technical composition of their registration dossiers are considerably analogous, with different regulatory demands tangible to specific questions related to each type of medicine. In the analyzed period (2009 to 2010), in order to portray the regulatory trend adopted by the Brazilian pharmaceutical sector, the categories of generic medicines and similar are the ones that submitted more requests for deferrals and registries in the country.

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Vacherot, Francis. "Étude de l'activité mitogène du facteur de croissance Heparin Affin Regulatory Peptide (HARP) et de son implication dans la physiologie et la physiopathologie de la prostate." Paris 12, 1996. http://www.theses.fr/1996PA120020.

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Notre laboratoire a purifie a partir de cerveau de buf un facteur de croissance ayant une forte affinite pour l'heparine appele harp (heparin affin regulatory peptide) egalement connu sous le nom de ptn (pleiotrophin). In vitro, cette molecule induit la croissance neuritique des neurones embryonnaires et des cellules pc12. Harp est egalement capable d'induire la croissance des cellules endotheliales, fibroblastiques, epitheliales et musculaires lisses. Cependant cette activite mitogene est contestee, certains auteurs pretendant qu'elle reflete la presence de contaminants de type fgfs dans les fractions purifiees d'harp. Dans le but de lever cette controverse, nous avons clone et les cellules nih-3t3 sont transfectees avec l'adnc humain de l'harp. Nous avons ainsi pu montrer que la proteine harp recombinante (harpr) purifiee a partir des surnageants de culture est neurotrope, mitogene et angiogene. Les analyses structurales revelent que la proteine recombinante purifiee existe sous deux formes. Une forme longue qui possede trois acides amines supplementaires du cote nh#2-terminal de la proteine se distingue d'une forme courte. Seule la forme longue induit la proliferation cellulaire. Nous avons ensuite montre que l'activite mitogene de l'harp etait modulee par l'heparine et que cette proteine est liee a des heparanes sulfates des structures pericellulaires des cellules qui le produisent. Dans le but d'etudier le role physologique et physiopathologique de l'harp, nous avons choisi un modele d'etude hormono-sensible qui est la prostate. In vitro, la dihydrotestosterone induit l'expression des arnm de l'harp par des cellules epitheliales de prostate normales (pnt-1a). Ces cellules comme d'autres cellules de lignees tumorales (du-145 et lncap) repondent a l'effet mitogene de ce facteur. Nous avons egalement montre, qu'in situ les arnm de l'harp sont localises exclusivement au niveau des cellules du stroma fibro-musculaire de prostates humaines normales ou atteintes d'adenomes comme de cancers. La proteine harp est localisee dans le mesenchyme. Elle n'est pas detectee dans les epitheliums de prostates normales et d'adenomes alors qu'elle l'est fortement au niveau des cellules epitheliales de cancers de prostate. Nous avons, apres transfection de l'adnc de l'harp dans les cellules epitheliales normales de prostate pnt-1a, montre que ces cellules surexpriment ce facteur de croissance et presentent une transformation de leur phenotype, caracterisee par une croissance en agar mou et une croissance clonale a faible quantite de serum. L'ensemble de ces resultats suggere d'une part que ce facteur de croissance soit implique dans les interactions mesenchyme-epitheliales via un mecanisme d'action de type paracrine vis a vis des cellules epitheliales, et d'autre part que l'harp ait un role important dans les processus de transformation cellulaire

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Di, Francesco Dimitri. "La doctrine administrative de la commande publique." Thesis, Paris 2, 2018. http://www.theses.fr/2018PA020024.

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Contrairement à la doctrine fiscale, la doctrine administrative de la commande publique, quand bien même son assise est ancienne, n’a constitué que récemment un objet d’étude. Cependant, étant un outil essentiel pour les administrations, la doctrine administrative démontre à nouveau l’unilatéralité de l’action publique au motif qu’elle est l’instrumentum par lequel la direction des affaires juridiques des ministères économiques et financiers (DAJ) propose une interprétation de ce droit technique. Une étude empirique et prospective de cette doctrine administrative doit conduire à mettre en lumière toutes ces sources souterraines du droit de la commande publique sur lesquelles l’ensemble des acteurs s’appuie
Contrary to the tax doctrine, the administrative doctrine of public contracts, even though its foundation is old, has only recently been an object of study. However, being an essential tool for the administrations, the administrative doctrine demonstrates the unilateral nature of the public action because it is the instrumentum by which the Direction of Legal Affairs of the economic and financial ministries (DAJ) gives an interpretation of this technical law field. An empirical and prospective study of this administrative doctrine should lead to highlighting all these underground sources of public contrats on which all the actors relies

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Dos, Santos Célia. "Implication de la région C-terminale de l'Héparin Affin Regulatory Peptide (HARP) dans l'inhibition de la prolifération des glioblastomes et mise en évidence d'interactions entre ce facteur de croissance et d'autres Heparin Binding Growth Factors (HBGFs)." Paris 11, 2010. http://www.theses.fr/2010PA11T082.

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Tir, Nesym. "Evolution de la réglementation des institutions financières : de la lutte anti-blanchiment à la conformité." Thesis, Université Côte d'Azur (ComUE), 2019. http://www.theses.fr/2019AZUR0007.

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La mondialisation des échanges, générant un accroissement des volumes de transactions financières, a été accompagnée par une mondialisation des activités criminelles. Les techniques de blanchiment se sont adaptées à cette réalité économique. La lutte anti-blanchiment est intrinsèquement un sujet complexe qui a mobilisé une volonté d’architecture ouverte entre les acteurs publics et une interdépendance entre les régulateurs et les institutions financières. Son objectif est de viser l’action des organisations criminelles transnationales qui ont su tirer profit de la congruence entre la sophistication financière et l’ère du numérique. La réglementation de ces dernières années, concernant la lutte anti-blanchiment d’argent et lutte contre le financement du terrorisme, a mis en relief l’émergence du droit souple avec, parallèlement, un changement paradigmatique pour les institutions financières qui se retrouvent désormais à appliquer des normes restrictives émanant du législateur et d’appliquer des normes de contrainte, ou incitatives, provenant de différentes autorités de régulation, générant parfois une perception de superposition réglementaire. Insérées dans le dispositif mondial de lutte anti blanchiment, les institutions financières doivent s’adapter cette inflation réglementaire qui persiste depuis plusieurs années. Ce changement de texture normative se caractérise par une combinaison de ces différents droits dont le mouvement ne cesse de se prolonger avec le droit de la régulation bancaire et financière. Ce droit de la régulation bancaire et financière invite les institutions financières à adopter une certaine élasticité dans la mise en place des dispositifs de conformité permettant la mise en oeuvre d’outils systémiques face à une complexité endémique de la délinquance financière. La mondialisation de la criminalité financière appelle à la nécessité de la mondialisation du droit via un système de contrôle adapté de la part des acteurs de la finance. Dans ce contexte, le juriste en conformité voit ses prérogatives revisitées et sa perception bouleversée par ce mouvement de plaque tectonique réglementaire
Globalization of trade and financial transactions have been followed by globalization of financial crime.Money laundering techniques have converged in light of this economic reality. Anti-Money laundering is considered like a complex topic wich includes interaction between regulator bodies and financial institutions. It aims to counter international criminal transactions taking advantage of financial innovation and digital evolution. The anti-money laundering regulation of recents years highlights soft law wich results new normative paradigm producing regulatory overlay.Inserted in anti-money laundering worldwide program, financial institutions have to deal with regulatory inflation that has lasted for several years. This normative mutation is defined by different laws combination whose movement continues to grow with banking and financial regulatory. This banking and financial regulatory requires financial institutions to put in place a flexibility compliance program with systemic tools to cope with white-collar complexity environment. Financial crime globalization needs globalization law and regulation wich uses financial institutions monitoring system. In this context, the compliance lawyer must adapt his perception and mission with respect to tectonic plate regulation movement

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Kinuthia, Wanyee. "“Accumulation by Dispossession” by the Global Extractive Industry: The Case of Canada." Thèse, Université d'Ottawa / University of Ottawa, 2013. http://hdl.handle.net/10393/30170.

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This thesis draws on David Harvey’s concept of “accumulation by dispossession” and an international political economy (IPE) approach centred on the institutional arrangements and power structures that privilege certain actors and values, in order to critique current capitalist practices of primitive accumulation by the global corporate extractive industry. The thesis examines how accumulation by dispossession by the global extractive industry is facilitated by the “free entry” or “free mining” principle. It does so by focusing on Canada as a leader in the global extractive industry and the spread of this country’s mining laws to other countries – in other words, the transnationalisation of norms in the global extractive industry – so as to maintain a consistent and familiar operating environment for Canadian extractive companies. The transnationalisation of norms is further promoted by key international institutions such as the World Bank, which is also the world’s largest development lender and also plays a key role in shaping the regulations that govern natural resource extraction. The thesis briefly investigates some Canadian examples of resource extraction projects, in order to demonstrate the weaknesses of Canadian mining laws, particularly the lack of protection of landowners’ rights under the free entry system and the subsequent need for “free, prior and informed consent” (FPIC). The thesis also considers some of the challenges to the adoption and implementation of the right to FPIC. These challenges include embedded institutional structures like the free entry mining system, international political economy (IPE) as shaped by international institutions and powerful corporations, as well as concerns regarding ‘local’ power structures or the legitimacy of representatives of communities affected by extractive projects. The thesis concludes that in order for Canada to be truly recognized as a leader in the global extractive industry, it must establish legal norms domestically to ensure that Canadian mining companies and residents can be held accountable when there is evidence of environmental and/or human rights violations associated with the activities of Canadian mining companies abroad. The thesis also concludes that Canada needs to address underlying structural issues such as the free entry mining system and implement FPIC, in order to curb “accumulation by dispossession” by the extractive industry, both domestically and abroad.

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Chiu, Chun-Huei, and 邱君慧. "ASEAN Regulatory Affairs Study on Generic Drugs." Thesis, 2017. http://ndltd.ncl.edu.tw/handle/zu3a3m.

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Moonsamy, Marlene Rose. "Correlation between tertiary education and pharmaceutical industry requirements for regulatory affairs pharmacists." Thesis, 2016. http://hdl.handle.net/10539/21549.

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A Research Report submitted to the Faculty of Health Sciences, University of Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Master of Science in Medicine Pharmacotherapy June 2016
In the pharmaceutical sector, the health of the public is protected by medicines regulatory authorities who enforce regulatory practices to be executed by pharmaceutical companies. In South Africa, the Medicines Control Council (MCC) describes these practice requirements via guidelines, which are based on the Medicines and Related Substances Control Act 101 of 1965. The Regulatory Affairs Department is often the first point of contact between the regulatory authority and the company. Regulatory affairs pharmacists therefore require broader skill sets than scientific and technical skills. Global expansion of regulatory affairs has resulted in significant skills shortage, for which a lack of education in regulatory affairs is partially responsible. Lack of communication between academia and industry further contributes to this skills shortage. In South Africa, the Pharmacy School curricula are approved by the South African Pharmacy Council (SAPC) in keeping with The Pharmacy Act 53 of 1974. Regulatory practices however, are determined by the Medicines and Related Substances Control Act. The aim of this study was to assess if there are inconsistencies in regulatory affairs between the pharmacy curriculum and job descriptions of regulatory affairs pharmacists, and to determine if graduating pharmacists entering industrial pharmacy are equipped for their role in regulatory affairs. The objectives were to examine regulatory education and regulatory practices in industry to assess deficiencies in the required competencies of a regulatory affairs pharmacist. The appropriate sections in Pharmacy curricula from all eight Pharmacy Schools in South Africa were examined to assess the level to which regulatory affairs is taught, and the job descriptions of regulatory affairs pharmacists were examined to assess the functional competencies required. Survey studies were conducted in the Pharmacy Schools and Pharmaceutical Industry to understand the gaps between what is taught and what is required in industry practice. The results showed that B.Pharm undergraduates were insufficiently prepared for their role in regulatory affairs, once they entered the Pharmaceutical Industry sector. Regulatory Affairs education is covered partially at undergraduate level but in some detail at a post-graduate level, in some Pharmacy Schools. Improvements are required to the current B.Pharm curricula, taking into account the Medicines Act 101 of 1965 and with MCC Guidelines, to accommodate regulatory affairs education. Collaboration between academia and industry has been proposed and employed in other countries and have been shown to be successful, hence this is also recommended for South Africa with most participants expressing a willingness to do so..
MB2016

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Liu, Sin-Wei, and 劉欣維. "The regulatory affairs study on Health Food of Taiwan, China, USA and Australia." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/4um3da.

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碩士
中國醫藥大學
製藥碩士學位學程
106
As the economy and the standard of living improve, the demand for health and wellness is rapidly increasing. Under the influence of the traditional Chinese concept of health, the functional food grows quickly and becomes a flourishing industry in Taiwan. According to the flourishing of functional food industry, Taiwan government legislated the law of Health food to strengthen the supervision and control in 1999. However, there are only four hundred registered Health Foods until now. This study focused on the requirements that may be unsatisfied in the regulatory affairs on Health Food by searching the laws and the competent authorities of Health Foods and related products. Chapters 2 to 5 introduce the supervision and control systems of health foods and related products in Taiwan, China, the United States and Australia. Each chapter start from the development status of health foods in these countries, then discuss the administrative of the competent authorities. Above all regulatory, this study focused on approval processes, scientific efficacy verification and the appropriate product labeling and advertising. Chapter 6 compares the different between Taiwan, China, the United States, and Australia by the approval processes, health claims, and labels of Health Food and its related products, and analysts the strengthen and weakness of Taiwan health industry and regulation system. From an industry perspective, the characteristics of emphasizing on academic research and quality management can win the trust of occidental world on products. However, the small domestic market and the lack of capital are common disadvantages for many Small and medium-sized enterprises in Taiwan. Focusing on the overseas Chinese market and conducting strategic alliances with local manufacturers may be the solutions to involve in the international market. In terms of regulations, the health food regulations are clearly defined and detailed, and the review units are professional and rigorous. They are a benign help to the health industry and consumers, but the government need to make more efforts on the insufficient health care efficacy assessment methods, the procrastination of examination, and the inadequate health food knowledge education by well planning.

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Ding, Yu-Xing, and 丁宇星. "Shaping Regulatory Affairs Strategy in Animal Healthcare Industry at a Country Level: The Case of China." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/xx3egk.

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碩士
國立政治大學
國際經營管理英語碩士學位學程(IMBA)
107
The fast-growing global demand for livestock-derived products and pet health care has driven the animal healthcare industry to develop safe, efficacious, and high-quality veterinary medicinal products. The commercialization of most veterinary medicinal products, similar to human medicine, requires the marketing authorization from regulatory authorities. However, the complexities of regulatory environment and inconsistent regulatory requirement at different markets have still been a hurdle for multinational companies to rapidly bring new products to the market, especially to China. The objective of this study is to provide a systemic analysis on China’s regulatory landscape as well as to help animal healthcare firms develop a well-structured and robust in-country regulatory affairs strategy in China.We started from examining existing regulatory challenges and conducting gap analysis on currently proposed solutions to regulators and industry. The roadmap comprising key driving forces and elements to the regulatory approval in China as well as potential roadblocks were analyzed and constructed. The proposed “Schematic of Regulatory Affairs Process” offers a practical approach for multinational animal healthcare firms to develop the most rewarding regulatory affairs strategy in China via capturing required forces driving to the regulatory approval of veterinary medicinal product.

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Δρόσου, Γεωργία. "Μελέτη του ρόλου του αυξητικού παράγοντα HARP (Heparin Affin Regulatory Peptide) στην αγγειογένεση in vivo." Thesis, 2007. http://nemertes.lis.upatras.gr/jspui/handle/10889/753.

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H HARP (heparin-affin regulatory peptide), γνωστή και ως πλειοτροπίνη (PTN), είναι ένας 18 kDa αυξητικός παράγοντας, ο οποίος έχει υψηλή συγγένεια για την ηπαρίνη. Η HARP έχει πολλαπλές βιολογικές δράσεις, όπως συμμετέχει στη ρύθμιση του κυτταρικού πολλαπλασιασμού, στη μετανάστευση και τη διαφοροποίηση. Επιπλέον η έκφραση της σχετίζεται με την φυσιολογική και καρκινική αγγειογένεση in vitro και in vivo. Στην παρούσα εργασία μελετήθηκε η έκφραση της HARP και των υποδοχέων της, ALK και RPTPβ/ζ, στις διάφορες ημέρες ανάπτυξης της CAM εμβρύου όρνιθας. Επίσης, μελετήθηκε η μείωση της έκφρασης της ενδογενούς HARP, με πλασμίδιο που φέρει την αντινοηματική αλληλουχία (AS-HARP), στην αγγειογένεση in vivo, στη φωσφορυλίωση των Εrk1,2 και στη λεμφαγγειογένεση της CAM εμβρύου όρνιθας. Ανάλυση κατά Western και RT-PCR στις διάφορες ημέρες ανάπτυξης του εμβρύου έδειξε ότι η έκφραση της HARP συμβαδίζει με τη δημιουργία νέων αγγείων στη CAM, ενώ η έκφραση των υποδοχέων της HARP στην CAM φαίνεται να είναι αυξημένη στα πρώτα στάδια ανάπτυξης του ιστού. Επίσης, η μείωση της έκφρασης της HARP μετά τη χορήγηση του πλασμιδίου AS-HARP, μείωσε τα επίπεδα της πρωτεΐνης, το μήκος των αγγείων και τη φωσφορυλίωση των Erk1/2 στο in vivo μοντέλο της CAM εμβρύου όρνιθας. Αντίθετα, η μείωση της έκφρασης της HARP μετά τη χορήγηση του πλασμιδίου AS-HARP, δεν επηρέασε τη λεμφαγγειογένεση της CAM εμβρύου όρνιθας. Σαν τελικό συμπέρασμα προκύπτει ότι η έκφραση της ενδογενούς HARP στην CAM εμβρύου όρνιθας είναι σημαντική για τη φυσιολογική αγγειογένεση in vivo.
Heparin-affin regulatory peptide (HARP), also known as pleiotrophin or heparin-binding growth-associated molecule, is an 18 kDa growth factor that has a high affinity for heparin. HARP is involved in the control of cellular proliferation, migration and differentiation. Moreover, there is a strong correlation between HARP expression and tumor growth and angiogenesis. In the present work, we studied the expression of HARP and its receptors, ALK and RPTPβ/ζ, during development of the chicken embryo chorioallantoic membrane (CAM), in relation to angiogenesis. By western blot analysis and RT-PCR, it was shown that HARP, ALK and RPTPβ/ζ expression increased at days of on-going angiogenesis and decreased at later time points. Transfection of CAMs with an anti-sense HARP gene construct led to a significant decrease in HARP amounts compared to vector control transfected CAMs, a significant decrease in the length of CAM blood vessels, and a decrease in the phosphorylation of Erk1/2. Contrary, transfection of CAMs with the anti-sense HARP gene construct had no influence in lymphangiogenesis of the chicken embryo chorioallantoic membrane (CAM). These data suggest that endogenous HARP is involved in angiogenesis in vivo.

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Dias, José Augusto Aleixo. "Contribution of medical affairs to an efficient management in the pharmaceutical industry." Doctoral thesis, 2019. http://hdl.handle.net/10773/25719.

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During the last decade the pharmaceutical industry (PI) operations became far more complex due to several structural and organizational changes, new legislation and pharmacoeconomic constraints. The role of Medical Affairs (MA) has been increasingly important and the interactions between PI and healthcare professionals (HCP) are currently much more based on science, than in marketing or commercial arguments. This thesis provides an in-depth description of the MA function, maps key areas of activity, challenges processes and opportunities, based on the feedback collected from PI professionals, HCP, regulatory authorities, payers and patient´s associations, while suggesting metrics to evaluate the activity and impact of such actions. To collect insights from these sources two questionnaires were sent to 400 pharmaceutical industry professionals and to 197 customers, addressing the most relevant topics of the MA contribution to strategic and operational activities, while identifying areas where there was greater perceived value of their activity. There were 169 responders to the first survey (colleagues), while 40 answers to the second one (customers). The importance of the MA on the overall results of the company was very high rated and, its contribution to strategic activities was seen as essential for the support of product launch, improvement of therapeutic adherence and partnerships with Patient’s Associations. Higher scores were also given to operational activities such as medical awareness/education and symposia preparation, internal training and advisory board management. A great deal of medical effort was also spent in content creation, preparation and review of materials, in medicine related responses, presentations, reimbursement dossiers, safety risk management, internal cross functional meetings, as well as, in dealing with customers. Digital and multichannel medical labor was still rated low, while the contribution for mobile applications and similar devices gained some interest. The number of medicines considered reasonable for a Medical Affairs professional to be responsible for, was two through three. Customer facing activity was found to be reasonable up to ten customers per medical full time equivalent (FTE). MA efficiency was considered to be better exercised if office based rather than home based, while clinical research was considered to be more efficient if performed by company resources than by clinical research organizations (CRO).For these colleagues, the most important driver for clinical research in our country was said to be interest/perceived value while, long approval timelines, lack of resources and low curriculum vitae impact were identified as major roadblocks. The customer’s experience with clinical trials was greater than with investigator initiated research (IIR) or other non-interventional studies. When recruiting a Medical Affairs person, the characteristics perceived as most relevant were: a problem solving attitude, flexibility, pro-activeness and competency. The most important factors impacting Medical Affairs retention were: opportunities for personal development, recognition and work conditions. The contribution of the Medical Affairs to the reputation and credibility of the pharmaceutical industry was very highly rated. Looking at the future, most colleagues forsee a greater involvement of MA in pharmaceutical opperations. The impact of the implementation of the European Federation of Pharmaceutical Industries and Associations (EFPIA) disclosure code of ethics and transparency governing the relations between pharma industry and HCP was considered to be high, while the pharmaceutical image was assessed as good. In the future, the majority of customers foresee greater Medical Affairs involvement, while patients as well as citizens, will have a greater participation on the decision making process of their own health. At the end, set of MA metrics on volume and impact is also suggested.
Durante a última década, a gestão das operações na indústria farmacêutica (PI) tornou-se mais complexa devido a várias mudanças estruturais e organizacionais das empresas, a nova legislação e às restrições orçamentais a nível nacional e internacional. O papel dos Assuntos Médicos/Medical Affairs (MA) tem vindo a ser cada vez mais importante e as interações entre empresas farmacêuticas e os profissionais de saúde (HCP), muito mais baseadas em ciência, do que em argumentos comerciais ou de marketing. Esta tese fornece uma descrição detalhada da função MA, mapeia as principais áreas de actividade, problemas, desafios e oportunidades, com base na informação recolhida junto de profissionais da indústria farmacêutica, HCP, autoridades regulamentares, pagadores e associações de doentes, ao mesmo tempo sugerindo métricas, para avaliar a actividade e o impacto de tais ações. Para recolha de dados elaborámos dois questionários que, foram enviados por email a 400 profissionais da indústria farmacêutica e a 197 clientes, abordando os tópicos mais relevantes da contribuição de MA para as atividades estratégicas e operacionais, identificando as áreas onde existe um maior valor percebido dessa acção. Foram recebidas 169 respostas ao primeiro inquérito (colegas) enquanto que 40 respostas ao segundo inquérito (clientes). Os resultados obtidos permitem concluir que a contribuição dos MA para os resultados globais da empresa e para as estratégias definidas foi muito alta, sendo essencial para o apoio ao lançamento dos medicamentos, melhoria da adesão terapêutica e colaboração com as associações de doentes. Foram igualmente salientadas as atividades operacionais, como as relacionadas com materiais educacionais e de actualização, preparação de simpósios, treino interno e de consultoria. Um grande esforço médico é igualmente investido na criação de conteúdos, preparação e revisão de materiais, bem como, nas respostas relacionadas com os medicamentos, planos de gestão de risco, contribuição para dossiês de reembolso, em reuniões internas de alinhamento e na interacção com clientes. O contributo médico para as actividades digitais e multicanal foi ainda classificado como pouco relevante, enquanto que, as aplicações móveis registaram interesse. O número de medicamentos considerado razoável para um profissional de MA ter sob sua responsabilidade foi de dois a três, enquanto que o número de clientes a acompanhar deveria rondar os dez. A eficiência destes profissionais foi considerada melhor se exercida a partir do escritório do que do domicílio, enquanto que, a investigação clínica foi considerada mais eficiente se realizada pelos recursos da empresa vs recursos contratados (CRO).Para estes colegas, alguns dos factores determinantes para a investigação clínica no nosso país foram: o interesse na investigação e valor percebido dessa participação, enquanto que, os longos tempos de aprovação, a falta de recursos e o baixo impacto no curriculum vitae, constituíram alguns dos principais obstáculos. A experiência dos clientes com os ensaios clínicos é maior do que com os estudos de iniciativa do investigador (IIR), ou outros estudos não-intervencionais (NIS). Ao recrutar um profissional para Assuntos Médicos/Medical Affairs, as características percebidas como mais relevantes foram: uma atitude visando a solução de problemas, flexibilidade, pró-atividade e competência. Os factores mais relevantes referidos como impactantes na retenção destes profissionais foram: as oportunidades de desenvolvimento pessoal, o reconhecimento e as condições de trabalho. A contribuição dos Assuntos Médicos/Medical Affairs para a reputação e credibilidade da indústria farmacêutica foi altamente reconhecida, prevendo no futuro um ainda maior envolvimento médico nas empresas. O impacto da implementação do Código de Ética e Transparência da Federação Europeia da Indústria Farmacêutica e Associações (EFPIA), que rege as relações entre a indústria farmacêutica com os profissionais de saúde, foi considerado elevado; enquanto que a sua imagem foi avaliada como boa. No futuro, prevê-se um envolvimento maior dos Assuntos Médicos/Medical Affairs nas operações da indústria farmacêutica, dos doentes e dos cidadãos, no processo de decisão sobre a sua saúde. No final sugerem-se um conjunto de métricas sobre a actividade de MA em termos de volume e de impacto.
Programa Doutoral em Ciências e Tecnologias da Saúde

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Τριπολιτσιώτη, Δήμητρα. "Ο αυξητικός παράγοντας HARP (Heparin Affin Regulatory Peptide) ενεργοποιεί έμμεσα τον υποδοχέα ALK (Anaplastic Lymphoma Kinase)." 2013. http://hdl.handle.net/10889/6264.

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Η HARP (Heparin Affin Regulatory Peptide) είναι ένας αυξητικός παράγοντας που δεσμεύεται στην ηπαρίνη και εμπλέκεται στη ρύθμιση της κυτταρικής διαφοροποίησης, του κυτταρικού πολλαπλασιασμού καθώς και της αγγειογένεσης. Υψηλές συγκεντρώσεις του αυξητικού παράγοντα HARP έχουν βρεθεί σε ανθρώπινους καρκινικούς όγκους, σε καρκινικές κυτταρικές σειρές, όπως επίσης και σε ορό ασθενών με διάφορους τύπους καρκίνου. Επιπλέον, είναι γνωστό ότι η HARP αποτελεί υπόστρωμα για διάφορα πρωτεολυτικά ένζυμα του κυτταρικού μικροπεριβάλλοντος, με αποτέλεσμα την παραγωγή ενεργών πεπτιδίων που μπορούν να έχουν παρόμοιες ή και αντίθετες δράσεις από το ολικό μόριο. Η HARP ασκεί τις βιολογικές τις δράσεις ύστερα από πρόσδεση στους διαμεμβρανικούς υποδοχείς SDC3, RPTPβ/ζ και ALK. Παρά την ταυτοποίηση του υποδοχέα ALK ως λειτουργικού υποδοχέα της HARP, μέχρι σήμερα υπάρχουν αντικρουόμενες απόψεις αναφορικά με την αλληλεπίδρασή του με τη HARP. Στην παρούσα εργασία μελετήθηκε η αλληλεπίδραση του αυξητικού παράγοντα HARP και του υποδοχέα ALK σε καρκινικά κύτταρα PC3 ανθρώπινου προστάτη. Τα αποτελέσματα έδειξαν ότι η HARP επάγει τη φωσφορυλίωση του ALK σε κύτταρα PC3, ωστόσο δεν είχε καμία επίδραση στην ενεργοποίηση του συγκεκριμένου υποδοχέα σε κύτταρα PC3 στα οποία είχε μειωθεί η συσσώρευση του RPTPβ/ζ. Παράλληλα χρησιμοποιήθηκαν ανασυνδυασμένα πεπτίδια που είχαν εκφραστεί ως πρωτεΐνες σύντηξης με τη θειοτρανσφεράση της γλουταθειόνης (GST) και αντιστοιχούσαν σε περιοχές του αυξητικού παράγοντα HARP [P(9-110), P(9-59), P(60-110)] που προκύπτουν ύστερα από πέψη με πλασμίνη. Ύστερα από πειράματα συγκατακρήμνισης βρέθηκε ότι ο ALK αλληλεπιδρά ισχυρά με το πεπτίδιο P(60-110) αποτέλεσμα το οποίο προέκυψε και ύστερα από μεωρύθμιση των επιπέδων έκφρασης του RPTPβ/ζ. Συμπερασματικά, στην παρούσα εργασία καταδεικνύεται η έμμεση αλληλεπίδραση του υποδοχέα ALK και του αυξητικού παράγοντα HARP, η οποία βρέθηκε ότι διαμεσολαβείται από τον υποδοχέα RPTPβ/ζ. Αποδεικνύεται επίσης ότι παρόλο που η αλληλεπίδραση των δύο αυτών μορίων δεν είναι ικανή να οδηγήσει στη φωσφορυλίωση του υποδοχέα ALK, τα δύο αυτά μόρια αλληλεπιδρούν βιοχημικά καθώς η αλληλουχία 60-110 των αμινοξέων της HARP αλληλεπιδρά ισχυρά και με τις δύο μορφές του υποδοχέα, με μοριακό βάρος 220 και 140 kDa αντίστοιχα.
HARP (Heparin Affin Regulatory Peptide) is a heparin-binding growth factor, involved in the regulation of cell differentiation, cell proliferation as well as in angiogenesis. Elevated concentrations of HARP have been detected in malignancies, in cancer cell lines, as well as in the plasma of patients with different types of cancer. It is also known that HARP is substrate for different proteases of the cell microenvironment, leading to the production of biological active peptides which can exert similar or even opposite biological activities to HARP. HARP exerts its biological actions after binding to the transmembrane receptors SDC3, RPTPβ/ζ and ALK. Even though ALK has been defined as a functional HARP receptor, contradictory results have been published concerning HARP-ALK interaction. In the present work, we studied the interaction of HARP growth factor with ALK transmembrane receptor using PC3 prostate cancer cells. It was shown that HARP induces the phosphorylation of ALK in PC3 cells, however no effect on ALK activation was observed in PC3 cells after RPTPβ/ζ knockdown. We also used recombinant gst-fused peptides corresponding to various fragments of HARP [P(9-110), P(9-59), P(60-110)] which result after cleavage with plasmin. After GST pull-down assays it was shown that ALK strongly binds to the P(60-110), result that was also taken after RPTPβ/ζ knockdown. Cumulatively, our results indicate that HARP-induced ALK phosphorylation is mediated by RPTPβ/ζ. It is also demonstrated that HARP interacts biochemically with ALK, since P(60-110) strongly binded both species of ALK (220 and 140 kDa).

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Torres, João Diogo Basso da Silva. "Intership Reports and Monograph titled "Understanding Quality by Design with Monoclonal Antibodies"." Master's thesis, 2017. http://hdl.handle.net/10316/83771.

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Relatório de Estágio do Mestrado Integrado em Ciências Farmacêuticas apresentado à Faculdade de Farmácia
O presente documento compreende os Relatórios de Estágio em Farmácia Comunitária e em Assuntos Regulamentares e Farmacovigilância, e a monografia intitulada "Understanding Quality by Design with Monoclonal Antibodies". Para cada relatório, foi realizada uma análise SWOT. Quality by Design não é um conceito novo para a Indústria Farmacêutica. De facto, foi introduzido na ICH Q8 como uma abordagem melhorada para o Desenvolvimento Farmacêutico, substituindo o Quality by Testing. Esta metodologia sistemática defende que a qualidade não pode ser testada no produto; em alternativa, a qualidade deve ser construída por design. O QbD garante a qualidade através da compreensão da performance do produto, do seu processo de fabrico, e de todas as variáveis que sobre ele podem ter algum impacto. Com o QbD, testes de libertação em tempo real podem substituir os testes no produto final, uma vez que o processo de fabrico desenhado produzirá um medicamento com a qualidade desejada. No entanto, a terminologia do QbD não é clara, e levanta mal-entendidos na Indústria e nas Autoridades. Subsequentemente, definir um Perfil de Qualidade Alvo para o Produto Acabado; identificar os Atributos Críticos de Qualidade do produto, e os Parâmetros de Processo Críticos do processo de fabrico; estabelecer um alargado Design Space e definir uma estratégia de controlo que inclui especificações (para a substância ativa, excipientes e produto acabado), e controlos (para cada etapa do processo de fabrico) não está a ser alcançado à velocidade desejada. Nos Estados Unidos da América, submissões por QbD já estão a ser aprovadas para produtos acabados de origem química. Quanto aos produtos biotecnológicos, esta não é uma prática comum. Embora a Indústria esteja a progredir para a aceitação e implementação do QbD, ainda existe uma necessidade de compreender e clarificar conceitos e expectativas. Esta dissertação foi escrita para clarificar alguns termos, e aborda o Desenvolvimento Farmacêutico através do QbD. Os exemplos providenciados respeitantes aos anticorpos monoclonais têm como objetivo clarificar alguns termos do QbD que ainda são mal compreendidos, e serve de oportunidade para refletir sobre a aplicação do QbD no desenvolvimento de anticorpos monoclonais.
The present document comprises the Internship Reports on Community Pharmacy and Regulatory Affairs and Pharmacovigilance, and the monograph titled "Understanding Quality by Design with Monoclonal Antibodies". For each report, a SWOT analysis was conducted. Quality by Design is not a new concept to Pharmaceutical Industry. In fact, it was introduced in ICH Q8 as an improved approach to Pharmaceutical Development, replacing Quality by Testing. This systematic methodology defends that quality cannot be tested into products; instead, quality should be built in by design. QbD assures quality by understanding the product performance, its manufacturing process, and all the variables that may have an impact on it. With QbD, Real-Time Release Testing can replace end-product testing, as the designed manufacturing process will produce a medicine with the desired quality. However, QbD terminology is not clear, and arises several misunderstandings within the Industry and Authorities. Subsequently, setting a drug product Quality Target Product Profile (QTPP); identifying Critical Quality Attributes (CQAs) of the drug product, and Critical Process Parameters (CPPs) of the manufacturing process; establishing a wide Design Space; and defining a control strategy that includes specifications (for the drug substance, excipients and drug product), and controls (for each step of the manufacturing process) is not being achieved at the most desired speed. In the United States of America, QbD based submissions are already being approved for chemical drug products. As for biotechnological products, this is not a common practice. Although the Industry is moving towards the acceptance and implementation of QbD, there is still a need to understand and clarify concepts and expectations. This dissertation was written to clarify some terms, and addresses Pharmaceutical Development through QbD. The examples provided regarding monoclonal antibodies intent to exemplify some QbD terms that are currently still misunderstood, and serves as an opportunity to reflect about the application of QbD in the development of monoclonal antibodies development.

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Πολυκράτης, Απόστολος. "Μελέτη της βιολογικής δράσης και του μηχανισμού μεταγωγής σήματος του αυξητικού παράγοντα HARP (Heparin Affin Regulatory Peptide) σε ενδοθηλιακά κύτταρα." 2005. http://nemertes.lis.upatras.gr/jspui/handle/10889/266.

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Η Heparin affin regulatory peptide (HARP) είναι ένας αυξητικός παράγοντας με μοριακό βάρος 18 kDa, που έχει μεγάλη συγγένεια με την ηπαρίνη. Είναι συντηρημένη μεταξύ διαφόρων ειδών και παρουσιάζει 50% ομολογία με τη Midkine και την RI-HBP. Οι πρωτεΐνες αυτές συγκροτούν μια σχετικά νέα οικογένεια αυξητικών παραγόντων που έχουν συγγένεια με την ηπαρίνη. Η HARP απομονώθηκε για πρώτη φορά από τον εγκέφαλο νεογέννητου βοός ως ένα μόριο που μπορεί να επάγει την προέκταση των νευρικών κυττάρων. Επίσης, εκφράζεται στη μήτρα, στους χόνδρους και στα οστά. Αρκετές αναφορές αποδεικνύουν ότι υπάρχει μεγάλη συσχέτιση μεταξύ της έκφρασης της HARP και της ανάπτυξης καρκινικού όγκου και της αγγειογένεσης. Υψηλά επίπεδα της πρωτεΐνης έχουν ανιχνευθεί σε πολλούς καρκινικούς όγκους, αλλά και κυτταρικές σειρές που προέρχονται από διάφορους τύπους καρκίνου σε ανθρώπους. Η HARP αποτελεί μιτογόνο παράγοντα για διάφορους τύπους ενδοθηλιακών κυττάρων, ενώ μπορεί να επάγει την αγγειογένεση in vivo και in vitro. Ασκεί τη βιολογική της δράση μετά από αλληλεπίδραση με πρωτεογλυκάνες της επιφάνειας του κυττάρου, όπως η N-συνδεκάνη, ή μετά από δέσμευση σε πιο ειδικούς υποδοχείς. Η RPTPβ/ζ, η εκκρινόμενη μορφή της (φωσφακάνη), αλλά και η κινάση ALK, έχει αναφερθεί ότι μπορούν να δεσμεύουν τη HARP και να συμμετέχουν στη μεταγωγή του σήματός της. Παλαιότερες αναφορές έχουν δείξει ότι η HARP μπορεί να επάγει τις MAP-κινάσες και το μονοπάτι PI3K-Akt, ενώ αναστολείς των Erk½, ή της PI3K καταστέλλουν τη σύνθεση του DNA που επάγεται από τη HARP. Επιπλέον, η Shc και οι Erk ½ φωσφορυλιώνονται μετά από επώαση κυττάρων με HARP. Ωστόσο, τα ενδοκυτταρικά σήματα ειδικών υποδοχέων της HARP προς την PI3K ή τις MAPK δεν έχουν ακόμα χαρακτηριστεί ικανοποιητικά. Στην εργασία αυτή μελετήσαμε την επίδραση της HARP στη μετανάστευση κυττάρων HUVEC, στη δημιουργία αυλών σε υπόστρωμα matrigel, καθώς και το μονοπάτι μεταγωγής σήματος που ενεργοποιείται από τη HARP. Τα αποτελέσματά μας δείχνουν ότι η HARP επάγει τη μετανάστευση και τη διαφοροποίηση των ενδοθηλιακών κυττάρων HUVEC μετά από δέσμευσή της στην RPTPβ/ζ. Η δέσμευση αυτή οδηγεί σε ενεργοποίηση της Src, της FAK, της PI3K και των Erk ½. Το ορθοβαναδικό νάτριο, η θειική χονδροϊτίνη-C, το ΡΡ1, η wortmannin, το LY294002 και το U0126 αναστέλλουν τη μεταγωγή σήματος της HARP, καθώς και την επαγωγή της μετανάστευσης και διαφοροποίησης των HUVEC. Επιπλέον, η μείωση της έκφρασης της RPTPβ/ζ με τη χρησιμοποίηση παρεμβαλλόμενου RNA παρεμποδίζει τα ενδοκυτταρικά σήματα, καθώς και την επαγωγή της μετανάστευσης και της διαφοροποίησης που επάγεται από τη HARP. Τα αποτελέσματα αυτά δείχνουν ότι η RPTPβ/ζ αποτελεί υποδοχέα της HARP σε ενδοθηλιακά κύτταρα και αποσαφηνίζουν το μονοπάτι μεταγωγής σήματος της HARP στα κύτταρα αυτά.
Heparin affin regulatory peptide (HARP) is an 18 kDa growth factor that has a high affinity for heparin. HARP is highly conserved among species and shares 50% homology with Midkine and RI-HBP. The above proteins constitute a relatively new family of growth factors with high affinity for heparin. HARP has been originally purified from perinatal rat brain as a molecule that induces neurite outgrowth. HARP is also expressed in uterus, cartilage and bone extracts. Several reports have established a strong correlation between HARP expression and tumour growth and angiogenesis. High levels of this protein were found in many human cancers and cell lines derived from human tumours. HARP has been reported to be mitogenic for different types of endothelial cells and angiogenic in vivo and in vitro. HARP exerts its biological activity through interactions with cell surface proteoglycans, such as N-syndecan, or binding to more specific cell surface receptors. Receptor-type protein tyrosine-phosphatase β/ζ (RPTPβ/ζ) and its secreted variant phosphacan, as well as ALK, have been recently reported to bind HARP and to be implicated in its signalling.HARP has been previously shown to activate both the MAPK and PI3K - Akt signalling axes. Inhibitors of Erk½ or PI3K inhibit DNA synthesis stimulated by HARP. Additionally, analysis of tyrosine phosphorylated proteins following HARP stimulation, revealed induction of Shc and Erk ½ phosphorylation. Nevertheless, the signals from specific receptors to PI3K or MAPK are not well documented. In the present work, we examined the effect of HARP on migration and tube formation on matrigel of HUVEC and investigated the signalling pathway induced by HARP. We report that HARP induces migration and differentiation of endothelial cells through binding to RPTPβ/ζ, leading to activation of Src, FAK, PI3K and Erk½. Sodium orthovanadate, chondroitin sulfate-C, PP1, wortmannin, LY294002 and U0126 inhibit HARP-mediated signalling and HARP-induced HUVEC migration and differentiation. In addition, RPTPβ/ζ suppression using siRNA technology, interrupts intracellular signals, as well as HUVEC migration and differentiation that are induced by HARP. These results establish the role of RPTPβ/ζ as a receptor of HARP in HUVEC and elucidate the HARP signalling pathway in endothelial cells.

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Κίτσου, Παρασκευή. "Η συνδεκάνη-3 διαμεσολαβεί τις βιολογικές δράσεις της HARP." Thesis, 2011. http://nemertes.lis.upatras.gr/jspui/handle/10889/4761.

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Η HARP (Heparin Affin Regulatory Peptide) είναι ένας αυξητικός παράγοντας ο οποίος εμφανίζει πλειάδα βιολογικών δράσεων εμπλεκόμενος στη διαφοροποίηση, τον πολλαπλασιασμό και τη μετανάστευση πολλών τύπων κυττάρων, καθώς και στην αγγειογένεση και την ανάπτυξη όγκων. Η HARP έχει χρονοειδικό και ιστοειδικό πρότυπο έκφρασης, υπερεκφράζεται όμως σε καρκινικές κυτταρικές σειρές, σε ανθρώπινους καρκινικούς όγκους και βρίσκεται σε υψηλή συγκέντρωση στον ορό του αίματος ασθενών με διάφορες μορφές καρκίνου. Η HARP ασκεί τις βιολογικές της δράσεις μετά από δέσμευση στους διαμεμβρανικούς υποδοχείς, SDC3, ALK και RPTPβ/ζ. Οι βιολογικές της δράσεις προσδιορίζονται από τη συνισταμένη των δράσεων που έχει κάθε υποδοχέας της, αντικατοπτρίζοντας τον περίπλοκο μηχανισμό δράσης της. Στη συγκεκριμένη εργασία μελετήσαμε τον τρόπο με τον οποίο η SDC3 διαμεσολαβεί τις βιολογικές δράσεις της HARP σε κύτταρα DU145 και PC3, κυτταρικές σειρές από καρκίνο ανθρώπινου προστάτη. Χρησιμοποιώντας την RNAi τεχνολογία, διαμολύναμε παροδικά τα κύτταρα με siRNA ειδικά σχεδιασμένο έναντι της SDC3, μειώνοντας τα επίπεδα έκφρασης της. Καλλιεργήσαμε κύτταρα, φυσιολογικά και μετασχηματισμένα, επιδράσαμε εξωγενώς με HARP και τα αποτελέσματα έδειξαν ότι και στις δύο καρκινικές κυτταρικές σειρές, η SDC3 είναι θετικός ρυθμιστής της επαγόμενης από τη HARP κυτταρικής προσκόλλησης και μετανάστευσης. Παράλληλα, μελετήσαμε την ενεργοποίηση μορίων που εμπλέκονται στο μονοπάτι μεταγωγής σήματος της SDC3 όπως της Src, Fak, Akt, Pten και Erk1/2. Τα αποτελέσματα έδειξαν ότι η ενεργοποίησή της SDC3 από τη HARP οδηγεί στην αύξηση των επιπέδων των pSrc, pFak, pAkt και p Erk1/2, ενώ, βρέθηκε ότι μειώνεται η φωσφορυλίωση της Pten. Συμπερασματικά, στην παρούσα εργασία μελετήθηκε η συμμετοχή της συνδεκάνης 3 στις βιολογικές δράσεις της HARP, καθώς και μόρια του σηματοδοτικού μονοπατιού μεταγωγής σήματος του υποδοχέα αυτού. Βρέθηκε ότι η HARP προσδενόμενη στον υποδοχέα αυτό, επάγει την προσκόλληση και μετανάστευση των κυττάρων, δράσεις που συνδέονται με την ανάπτυξη όγκων και τη μετάσταση καρκινικών κυττάρων.
HARP (Heparin Affin Regulatory Peptide), also known as Pleiotrophin, is a growth factor involved in several biological actions such as induction of cellular proliferation, migration and angiogenesis. Elevated concentrations of this growth factor are found in many tumours, as well as in the plasma of patients with different types of cancer. HARP exerts its actions after binding to the transmembrane receptors RPTP β/ζ, ALK and N-Syndecan (SDC3). In the present work, we studied the role of the transmembrane receptor SDC3 in the biological actions of HARP. We used DU145 and PC3 transiently transfected with specific siRNA to downregulate the accumulation of SDC3. Our results show that HARP binds to SDC3 and induces the cell adhesion and migration of DU145 and PC3 cells. We also studied the signal transduction through SDC3 receptor and the activation of signaling molecules such as Src, Fak, Akt, Pten and Erk 1/2. Our results revealed that HARP induces the phosphorylation of Src kinase, Fak and Erk1/2 after binding to SDC3 in both DU145 and PC3 cells. Also, HARP increases Akt signaling cascade in PC3 cells, while it suppresses the signaling cascade induced by PTEN in DU145 cells. Consequently, HARP interaction with SDC3, results in the activation of SDC3, which in turn triggers a signal transduction pathway that leads to specific biological cell responses activates other cytoplasmic effectors. Therefore, there starts a signaling cascade that targets specific genes and cell response. In conclusion, our results indicate that SDC3 contributes, as a positive regulator, to HARP-dependent cell adhesion and migration in both DU145 and PC3 cells.

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Silva, Marta Isabel de Melo. "Internship Reports and Monograph entitled "Process Analytical Technology: principles and applications"." Master's thesis, 2017. http://hdl.handle.net/10316/83782.

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Relatório de Estágio do Mestrado Integrado em Ciências Farmacêuticas apresentado à Faculdade de Farmácia
O presente trabalho foi realizado para defesa do Relatório de Estágio em Farmácia Comunitária, do Relatório de Estágio em Indústria Farmacêutica e da Monografia intitulada “Process Analytical Technology: principles and applications”. Assim, encontra-se dividido em três partes, cada uma destinada à exploração de cada uma das atividades acima mencionadas. O Relatório de Estágio em Farmácia Comunitária assenta numa análise SWOT ao estágio realizado na Farmácia Miranda, onde é feita uma abordagem crítica aos pontos fortes, pontos fracos, oportunidades e ameaças aplicados ao estágio. Paralelamente, é feita uma confrontação com a formação académica e a sua preponderância nas tarefas realizadas, sendo tal complementada com a apresentação de casos práticos que demonstram os conhecimentos e experiência adquiridos. Igualmente, o Relatório de Estágio em Indústria Farmacêutica descreve a minha experiência, enquanto estagiária, na consultora farmacêutica Owlpharma – Consulting, Lda. São enumeradas todas as tarefas realizadas nas diferentes áreas de atuação da empresa e a importância do estágio para o desenvolvimento de diversas competências. A última parte do trabalho, descrita numa língua diferente do restante documento (inglês), é relativa à Monografia elaborada. Seguindo o tema supracitado, é feita uma apresentação e explicação dos princípios e aplicações das tecnologias analíticas em processo no fabrico farmacêutico, e os benefícios inerentes a essa aplicação. A análise da aplicação das tecnologias permite concluir que as duas principais vantagens são a libertação em tempo real e o fabrico contínuo dos medicamentos.
The present work was prepared based on the Internship Report on Community Pharmacy, the Internship Report on Pharmaceutical Industry and the Monograph entitled “Process Analytical Technology: principles and applications”. Thus, is divided in three parts, each destined to the explanation of each of the activities mentioned above. The Internship Report of Community Pharmacy is based on a SWOT analysis of the internship at Farmácia Miranda, where a critical approach to the strengths, weaknesses, opportunities and threats is taken. At the same time, a comparison is made with the academic training and its importance in the accomplished tasks. Such is complemented with the presentation of practical cases that demonstrate the knowledge and experience acquired. Similarly, the Internship Report on Pharmaceutical Industry describes my experience as a trainee in the pharmaceutical consulting firm Owlpharma – Consulting, Lda. All the activities performed in the different areas of the company and the importance of the internship for the development of several skills are listed. The last part of the document, written in a different language from the rest of the document (English), presents the Monograph. Following the aforementioned theme, a presentation and explanation of the principles and applications of process analytical technologies in the pharmaceutical manufacture is made, as well of its benefits. The analysis of the application of these technologies allowed to conclude that the two main advantages are real-time release and continuous manufacturing of drug products.

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Abreu, Patrícia da Silva. "Relatórios de Estágio e Monografia intitulada “Óleos essenciais no tratamento da Acne”." Master's thesis, 2021. http://hdl.handle.net/10316/99168.

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Relatório de Estágio do Mestrado Integrado em Ciências Farmacêuticas apresentado à Faculdade de Farmácia
Este documento está dividido em três partes. A primeira e segunda parte dizem respeito aos relatórios de estágio referentes aos estágios efetuados, enquanto a terceira parte refere-se à monografia por mim redigida.Uma das etapas finais do ciclo de estudos do Mestrado Integrado em Ciências Farmacêuticas da Faculdade de Farmácia da Universidade de Coimbra (MICF) diz respeito ao estágio curricular, tendo como objetivo principal a consolidação de conhecimentos previamente adquiridos e a sua aplicação no contexto de prática profissional. O contacto com a realidade profissional é extremamente importante uma vez que contribui para o desenvolvimento de várias competências e conhecimentos antes da entrada no mercado de trabalho. Neste sentido, estes relatórios de estágio, apresentados sob a forma de análise SWOT (Strengths, Weaknesses, Opportunities, Threats) procuram dar ênfase, de um ponto de vista interno, aos pontos fortes e fracos dos meus estágios e, de um ponto de vista externo, às oportunidades e ameaças sentidas no decorrer dos mesmos. O local escolhido para a realização do primeiro estágio foi a Farmácia Estádio, em Coimbra, sob a orientação do Dr. André Paiva, tendo sido uma experiência única e muito gratificante. Para além do estágio curricular em Farmácia Comunitária, a Faculdade de Farmácia permite-nos realizar um outro na área do medicamento, sendo-nos possível escolher entre o setor hospitalar, regulamentar ou industrial. Esta oportunidade que nos é dada, através de diversos protocolos acordados entre a faculdade e as várias entidades das diversas áreas, é de extrema importância porque nos dá a possibilidade de ter uma visão mais abrangente do papel do farmacêutico nos vários setores, permitindo-nos contactar com novas experiências e realidades, contribuindo para o desenvolvimento de várias competências e conhecimentos, dotando-nos de ferramentas imprescindíveis e preparando-nos, assim, para a entrada no mercado de trabalho. Assim sendo, optei por realizar a segunda parte do meu estágio na Pharmilab, uma empresa de consultoria especializada no setor cosmético, tendo decorrido entre os meses de janeiro a abril, sob a orientação do Dr. Daniel Ribeiro. Este relatório de estágio, apresentado sob a forma de análise SWOT (Strengths, Weaknesses, Opportunities, Threats) procura dar ênfase, de um ponto de vista interno, aos pontos fortes e fracos do meu estágio e, de um ponto de vista externo, às oportunidades e ameaças sentidas no decorrer do mesmo, tendo em conta a sua pertinência e enquadramento no plano de estudos do MICF. A terceira e última parte deste documento, diz respeito à monografia intitulada “Óleos essenciais no tratamento da Acne”. A acne vulgar é uma patologia inflamatória crónica da unidade pilossebácea, cuja causa é atribuída a vários fatores que se relacionam entre si, dos quais se destacam o aumento da produção de sebo, a alteração do processo de queratinização, a colonização e proliferação de bactérias e a inflamação da unidade pilossebácea.Apesar de não constituir um risco para a vida, a acne tem repercussões moderadas na qualidade de vida dos indivíduos que a têm, estando associada a níveis elevados de depressão e ansiedade, com grande impacto na autoestima, ocasionando problemas sociais e emocionais, muitas vezes semelhantes aos de outras doenças crónicas.Esta patologia apresenta-se principalmente sob a forma de lesões, destacando-se os comedões, as pápulas e as pústulas, sendo que, em casos mais graves, poderá manifestar-se através de nódulos, quistos e/ou cicatrizes, afetando principalmente a face, pescoço, peito, ombros e costas.Se não for tratada convenientemente, sobretudo em indivíduos com acne severa nos estados mais iniciais da patologia, podem originar-se cicatrizes profundas, de difícil resolução, que podem permanecer durante toda a vida.A terapêutica atualmente utilizada para esta patologia revela alguns efeitos secundários e está associada ao aparecimento de resistências bacterianas, factos esses que contribuem para a diminuição da adesão ao tratamento convencional. Deste modo, têm-se desenvolvido esforços no sentido de alcançar novas alternativas e dado especial atenção aos óleos essenciais no tratamento de algumas doenças cutâneas, nas quais a acne se insere.Nas últimas décadas, vários estudos têm comprovado que os óleos essenciais possuem atividades biológicas interessantes com capacidade de poderem ser utilizados como coadjuvantes ou até mesmo em substituição dos tratamentos atualmente utilizados para o tratamento da acne, destacando-se as atividades antibacterianas, antifúngicas e anti-inflamatórias, contra uma grande variedade de microrganismos.Esta monografia consiste numa revisão bibliográfica sobre a patologia da acne, onde se abordam aspetos como a sua epidemiologia, fisiopatologia, manifestações clínicas e tratamentos utilizados, bem como a utilização de óleos essenciais como futuros tratamentos desta doença.
This document is divided into three parts. The first and second part concern the internship reports referring to the internships carried out, while the third part refers to the monograph written by me.One of the final stages of the study cycle of the Integrated Master in Pharmaceutical Sciences at the Faculty of Pharmacy of the University of Coimbra (MICF) concerns the curricular internship, with the main objective of consolidating previously acquired knowledge and its application in the context of professional practice . Contact with the professional reality is extremely important as it contributes to the development of various skills and knowledge before entering the labor market. In this sense, these internship reports, provide in a form of SWOT analysis (Strengths, Weaknesses, Opportunities, Threats) seek to emphasize, from an internal point of view, the strengths and weaknesses of my internships and, from an internal point of view external, to opportunities and corrected without arising from them. The location chosen for the realization of the first internship was the Estádio Farmácia, in Coimbra, under the supervision of Dr. André Paiva, having been a unique and very rewarding experience.In addition to the curricular internship in Community Pharmacy, the Faculty of Pharmacy allows us to carry out another in the field of medicine, allowing us to choose between the hospital, regulatory or industrial sector. This opportunity that is given to us, through various protocols agreed between the faculty and as various entities from different areas, is extremely important because it gives us the possibility of having a more expanded view of the role of the pharmacist in the various sectors, allowing us to contact with new experiences and realities, contributing to the development of various skills and knowledge, providing us with essential tools and thus preparing us to enter the labor market. Therefore, I chose to do a second part of my internship at Pharmilab, a consulting company specialized in the cosmetic sector, which took place from January to April, under the guidance of Dr. Daniel Ribeiro.This internship report, presented as a SWOT analysis (Strengths, Weaknesses, Opportunities, Threats) seeks to emphasize, from an internal point of view, the strengths and weaknesses of my internship and, from an external point of view, the opportunities and felt during the course, taking into account its relevance and framework in the MICF study plan.The third and last part of this document concerns the monograph entitled “Essential Oils in the Treatment of Acne”.Acne vulgaris is a chronic inflammatory pathology of the pilosebaceous unit, the cause of which is attributed to several factors that are interrelated, among which the increase in sebum production, alteration of the keratinization process, colonization and proliferation of bacteria and inflammation of the pilosebaceous unit.Despite not being a risk to life, acne has moderate repercussions on the quality of life of individuals who have it, being associated with high levels of depression and anxiety, with a great impact on self-esteem, causing social and emotional problems, often similar those of other chronic diseases.This pathology presents itself mainly in the form of lesions, especially comedones, papules and pustules, and, in more severe cases, it can manifest itself through nodules, cysts and/or scars, mainly affecting the face , neck, chest, shoulders and back.If it is not properly treated, especially in individuals with severe acne in the earliest stages of the pathology, deep scars can be created, difficult to resolve, which can remain throughout life.The therapy currently used for this pathology reveals some side effects and is associated with the appearance of bacterial resistance, facts that contribute to the decrease in adherence to conventional treatment. Thus, efforts have been made to find new alternatives and pay special attention to essential oils in the treatment of some skin diseases, in which acne is involved.In recent decades, several studies have proven that essential oils have interesting biological activities with the ability to be used as supporting or even in replacement of treatments currently used for the treatment of acne, highlighting the antibacterial, antifungal and anti- inflammatory, against a wide variety of microorganisms.This monograph consists of a literature review on the pathology of acne, which addresses aspects such as its epidemiology, pathophysiology, clinical manifestations and treatments used, as well as the use of essential oils as future treatments for this disease.

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Abreu, Patrícia da Silva. "Relatórios de Estágio e Monografia intitulada “Óleos essenciais no tratamento da Acne”." Master's thesis, 2021. http://hdl.handle.net/10316/99177.

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Relatório de Estágio do Mestrado Integrado em Ciências Farmacêuticas apresentado à Faculdade de Farmácia
Este documento está dividido em três partes. A primeira e segunda parte dizem respeito aos relatórios de estágio referentes aos estágios efetuados, enquanto a terceira parte refere-se à monografia por mim redigida.Uma das etapas finais do ciclo de estudos do Mestrado Integrado em Ciências Farmacêuticas da Faculdade de Farmácia da Universidade de Coimbra (MICF) diz respeito ao estágio curricular, tendo como objetivo principal a consolidação de conhecimentos previamente adquiridos e a sua aplicação no contexto de prática profissional. O contacto com a realidade profissional é extremamente importante uma vez que contribui para o desenvolvimento de várias competências e conhecimentos antes da entrada no mercado de trabalho. Neste sentido, estes relatórios de estágio, apresentados sob a forma de análise SWOT (Strengths, Weaknesses, Opportunities, Threats) procuram dar ênfase, de um ponto de vista interno, aos pontos fortes e fracos dos meus estágios e, de um ponto de vista externo, às oportunidades e ameaças sentidas no decorrer dos mesmos. O local escolhido para a realização do primeiro estágio foi a Farmácia Estádio, em Coimbra, sob a orientação do Dr. André Paiva, tendo sido uma experiência única e muito gratificante. Para além do estágio curricular em Farmácia Comunitária, a Faculdade de Farmácia permite-nos realizar um outro na área do medicamento, sendo-nos possível escolher entre o setor hospitalar, regulamentar ou industrial. Esta oportunidade que nos é dada, através de diversos protocolos acordados entre a faculdade e as várias entidades das diversas áreas, é de extrema importância porque nos dá a possibilidade de ter uma visão mais abrangente do papel do farmacêutico nos vários setores, permitindo-nos contactar com novas experiências e realidades, contribuindo para o desenvolvimento de várias competências e conhecimentos, dotando-nos de ferramentas imprescindíveis e preparando-nos, assim, para a entrada no mercado de trabalho. Assim sendo, optei por realizar a segunda parte do meu estágio na Pharmilab, uma empresa de consultoria especializada no setor cosmético, tendo decorrido entre os meses de janeiro a abril, sob a orientação do Dr. Daniel Ribeiro. Este relatório de estágio, apresentado sob a forma de análise SWOT (Strengths, Weaknesses, Opportunities, Threats) procura dar ênfase, de um ponto de vista interno, aos pontos fortes e fracos do meu estágio e, de um ponto de vista externo, às oportunidades e ameaças sentidas no decorrer do mesmo, tendo em conta a sua pertinência e enquadramento no plano de estudos do MICF. A terceira e última parte deste documento, diz respeito à monografia intitulada “Óleos essenciais no tratamento da Acne”. A acne vulgar é uma patologia inflamatória crónica da unidade pilossebácea, cuja causa é atribuída a vários fatores que se relacionam entre si, dos quais se destacam o aumento da produção de sebo, a alteração do processo de queratinização, a colonização e proliferação de bactérias e a inflamação da unidade pilossebácea.Apesar de não constituir um risco para a vida, a acne tem repercussões moderadas na qualidade de vida dos indivíduos que a têm, estando associada a níveis elevados de depressão e ansiedade, com grande impacto na autoestima, ocasionando problemas sociais e emocionais, muitas vezes semelhantes aos de outras doenças crónicas.Esta patologia apresenta-se principalmente sob a forma de lesões, destacando-se os comedões, as pápulas e as pústulas, sendo que, em casos mais graves, poderá manifestar-se através de nódulos, quistos e/ou cicatrizes, afetando principalmente a face, pescoço, peito, ombros e costas.Se não for tratada convenientemente, sobretudo em indivíduos com acne severa nos estados mais iniciais da patologia, podem originar-se cicatrizes profundas, de difícil resolução, que podem permanecer durante toda a vida.A terapêutica atualmente utilizada para esta patologia revela alguns efeitos secundários e está associada ao aparecimento de resistências bacterianas, factos esses que contribuem para a diminuição da adesão ao tratamento convencional. Deste modo, têm-se desenvolvido esforços no sentido de alcançar novas alternativas e dado especial atenção aos óleos essenciais no tratamento de algumas doenças cutâneas, nas quais a acne se insere.Nas últimas décadas, vários estudos têm comprovado que os óleos essenciais possuem atividades biológicas interessantes com capacidade de poderem ser utilizados como coadjuvantes ou até mesmo em substituição dos tratamentos atualmente utilizados para o tratamento da acne, destacando-se as atividades antibacterianas, antifúngicas e anti-inflamatórias, contra uma grande variedade de microrganismos.Esta monografia consiste numa revisão bibliográfica sobre a patologia da acne, onde se abordam aspetos como a sua epidemiologia, fisiopatologia, manifestações clínicas e tratamentos utilizados, bem como a utilização de óleos essenciais como futuros tratamentos desta doença.
This document is divided into three parts. The first and second part concern the internship reports referring to the internships carried out, while the third part refers to the monograph written by me.One of the final stages of the study cycle of the Integrated Master in Pharmaceutical Sciences at the Faculty of Pharmacy of the University of Coimbra (MICF) concerns the curricular internship, with the main objective of consolidating previously acquired knowledge and its application in the context of professional practice . Contact with the professional reality is extremely important as it contributes to the development of various skills and knowledge before entering the labor market. In this sense, these internship reports, provide in a form of SWOT analysis (Strengths, Weaknesses, Opportunities, Threats) seek to emphasize, from an internal point of view, the strengths and weaknesses of my internships and, from an internal point of view external, to opportunities and corrected without arising from them. The location chosen for the realization of the first internship was the Estádio Farmácia, in Coimbra, under the supervision of Dr. André Paiva, having been a unique and very rewarding experience.In addition to the curricular internship in Community Pharmacy, the Faculty of Pharmacy allows us to carry out another in the field of medicine, allowing us to choose between the hospital, regulatory or industrial sector. This opportunity that is given to us, through various protocols agreed between the faculty and as various entities from different areas, is extremely important because it gives us the possibility of having a more expanded view of the role of the pharmacist in the various sectors, allowing us to contact with new experiences and realities, contributing to the development of various skills and knowledge, providing us with essential tools and thus preparing us to enter the labor market. Therefore, I chose to do a second part of my internship at Pharmilab, a consulting company specialized in the cosmetic sector, which took place from January to April, under the guidance of Dr. Daniel Ribeiro.This internship report, presented as a SWOT analysis (Strengths, Weaknesses, Opportunities, Threats) seeks to emphasize, from an internal point of view, the strengths and weaknesses of my internship and, from an external point of view, the opportunities and felt during the course, taking into account its relevance and framework in the MICF study plan.The third and last part of this document concerns the monograph entitled “Essential Oils in the Treatment of Acne”.Acne vulgaris is a chronic inflammatory pathology of the pilosebaceous unit, the cause of which is attributed to several factors that are interrelated, among which the increase in sebum production, alteration of the keratinization process, colonization and proliferation of bacteria and inflammation of the pilosebaceous unit.Despite not being a risk to life, acne has moderate repercussions on the quality of life of individuals who have it, being associated with high levels of depression and anxiety, with a great impact on self-esteem, causing social and emotional problems, often similar those of other chronic diseases.This pathology presents itself mainly in the form of lesions, especially comedones, papules and pustules, and, in more severe cases, it can manifest itself through nodules, cysts and/or scars, mainly affecting the face , neck, chest, shoulders and back.If it is not properly treated, especially in individuals with severe acne in the earliest stages of the pathology, deep scars can be created, difficult to resolve, which can remain throughout life.The therapy currently used for this pathology reveals some side effects and is associated with the appearance of bacterial resistance, facts that contribute to the decrease in adherence to conventional treatment. Thus, efforts have been made to find new alternatives and pay special attention to essential oils in the treatment of some skin diseases, in which acne is involved.In recent decades, several studies have proven that essential oils have interesting biological activities with the ability to be used as supporting or even in replacement of treatments currently used for the treatment of acne, highlighting the antibacterial, antifungal and anti- inflammatory, against a wide variety of microorganisms.This monograph consists of a literature review on the pathology of acne, which addresses aspects such as its epidemiology, pathophysiology, clinical manifestations and treatments used, as well as the use of essential oils as future treatments for this disease.

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Figueiredo, Alina Maria Moreira de. "Medicines registration in Portuguese-speaking African countries, focusing in the following countries: Angola, Cap Verde and Mozambique." Master's thesis, 2015. http://hdl.handle.net/10773/15537.

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Mestrado em Biomedicina Farmacêutica
This work aims to present the regulation perspective on the medicines registration in PALOPs – Países Africanos de Língua Oficial Portuguesa (Portuguese‐speaking African countries), their regulatory requirements, constraints and opportunities, focusing on the following countries: Angola, Cape Verde and Mozambique. This thesis has as purpose to deepen and systematize knowledge with regard to the registration procedure of medicines in the selected countries. Regulatory perspective is framed in the context of the health sector and its development and national regulatory agencies in developing countries in Africa. The information used was gathered from the Ministry of Health Websites in each country and/or regulatory authority of medicines, international entities and bibliography regarding the PALOP and other African countries. Health systems existing in referred countries are subject to a SWOT analysis, with discussion of the strengths and improvement opportunities for each one. The regulatory authorities of developing countries in Africa face problems of lack of funding and human resources but there is an improvement effort by several countries including the adoption of legislation in order to ensure a tighter control of medicines that are placed on the market. The drug registration is a crucial process in the evaluation of medicinal products with the purpose to place them on the market, seeking to minimize the use of low quality drugs, ineffective or counterfeit. The authorities of developing countries face the challenge of evaluating drugs without prior evaluation by more experienced officials, and simultaneously requiring qualified personnel for this purpose. As a result have been observed in recent years efforts to implement procedures, adoption of international guidelines and training of qualified personnel. It has been adopted in some countries the registration process by recognition of the evaluation made by more experienced authorities.
O presente trabalho propõe apresentar a perspectiva regulamentar do registo de medicamentos nos PALOPs – Países Africanos de Língua Oficial Portuguesa, respectivos requisitos regulamentares, dificuldades e oportunidades, com enfoque nos seguintes países: Angola, Cabo Verde e Moçambique. Esta tese tem como finalidade aprofundar e sistematizar os conhecimentos no que respeita ao registo de medicamentos nos países seleccionados. A perspectiva regulamentar é enquadrada no contexto do sector da Saúde e seu desenvolvimento e das Agências Nacionais Reguladoras dos países em desenvolvimento, no continente africano. A informação utilizada foi recolhida dos sítios Web do Ministério da saúde de cada país e/ou autoridade reguladora dos medicamentos, organismos internacionais competentes e bibliografia referente aos PALOPs e outros países africanos. Os sistemas de saúde actualmente existentes nos países referidos são alvo de uma análise SWOT, com discussão dos pontos fortes e oportunidades de melhoria para cada um. As autoridades regulamentares dos países africanos em desenvolvimento enfrentam problemas de falta de recursos financeiros e humanos, existindo no entanto um esforço de melhoria nomeadamente na adoção de legislação de forma a garantir um controlo mais apertado dos medicamentos que são colocados no mercado. O registo de medicamentos é um processo fundamental no que respeita à avaliação dos medicamentos com vista à sua colocação no mercado, procurando minimizar o uso de fármacos de baixa qualidade, ineficazes ou falsificados. As autoridades dos países em desenvolvimento enfrentam o desafio de avaliar fármacos sem a mesma ter sido realizada previamente por outras autoridades mais experientes, necessitando simultaneamente de técnicos qualificados para esse efeito. Como resultado têm sido observados nos últimos anos esforços na implementação de procedimentos, adoção de orientações internacionais e na formação de pessoal qualificado. Tem sido adotado em alguns países o processo de registo por reconhecimento da avaliação feita por autoridades mais experientes.

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Ηλιάδου, Ελένη. "Σχεδιασμός, σύνθεση και μελέτη βιολογικών δράσεων πεπτιδίων της HARP." Thesis, 2010. http://nemertes.lis.upatras.gr/jspui/handle/10889/3209.

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Η Heparin affin regulatory peptide (HARP) είναι ένας αυξητικός παράγοντας με μοριακό βάρος 18 kDa, που έχει μεγάλη συγγένεια με την ηπαρίνη. Είναι συντηρημένη μεταξύ διαφόρων ειδών και παρουσιάζει 50% ομολογία με τη Midkine και την RI-HBP. Οι πρωτεΐνες αυτές συγκροτούν μια σχετικά νέα οικογένεια αυξητικών παραγόντων που έχουν συγγένεια με την ηπαρίνη. Η HARP απομονώθηκε για πρώτη φορά από τον εγκέφαλο νεογέννητου βοός ως ένα μόριο που μπορεί να επάγει την προέκταση των νευρικών κυττάρων. Επίσης, εκφράζεται στη μήτρα, στους χόνδρους και στα οστά. Αρκετές αναφορές αποδεικνύουν ότι υπάρχει μεγάλη συσχέτιση μεταξύ της έκφρασης της HARP και της ανάπτυξης καρκινικού όγκου και της αγγειογένεσης. Η HARP αποτελεί μιτογόνο παράγοντα για διάφορους τύπους ενδοθηλιακών κυττάρων, ενώ μπορεί να επάγει την αγγειογένεση in vivo και in vitro. Ασκεί τη βιολογική της δράση μετά από αλληλεπίδραση με πρωτεογλυκάνες της επιφάνειας του κυττάρου, όπως η N-συνδεκάνη, ή μετά από δέσμευση σε πιο ειδικούς υποδοχείς. Η RPTPβ/ζ, η εκκρινόμενη μορφή της (φωσφακάνη), αλλά και η κινάση ALK, έχει αναφερθεί ότι μπορούν να δεσμεύουν τη HARP και να συμμετέχουν στη μεταγωγή του σήματός της. Ο κύριος σκοπός αυτής της διατριβής είναι η μελέτη της δομής και της δράσης της HARP, χρησιμοποιώντας μικρότερα τμήματα της HARP τα οποία τα έχουμε βιοτινυλιώσει για να διερευνήσουμε τις περαιτέρω δράσεις της, τους διάφορους μηχανισμούς και με ποιους υποδοχείς αλληλεπιδρά. Τα βιοτινυλιωμένα-σεσημασμένα πεπτίδια αποτελούν χρήσιμα εργαλεία για την βιοτεχνολογία, σε διάφορες εφαρμογές στερεής φάσης ανοσολογικών δοκιμών καθώς και τον εντοπισμό των υποδοχέων. Τα συνθετικά πεπτίδια της HARP συντέθηκαν με μεθοδολογία Fmoc/t-Bu σε στερεά φάση χρησιμοποιώντας ως στερεό υπόστρωμα τη 2-χλωροτρίτυλ-ρητίνη για την παραλαβή μιας ελεύθερης αμινοομάδας (ΝΗ2) και C-τελικού καρβοξυλικού οξέος αντίστοιχα. Για την παραγωγή βιοτινυλιωμένων πεπτιδίων, περιλαμβάνει τον σχηματισμό ενός δεσμού: της ελεύθερη αμινοομάδα με την βιοτίνη στην διάρκεια της πεπτιδικής σύνθεσης στερεής φάσης. Επειδή η βιοτίνη έχει μικρή διαλυτότητα στα διαλύματα της πεπτιδικής σύνθεσης χρησιμοποιούμε τους προσχηματισμένους ενεργοποιημένους εστέρες όπως την βιοτίνη- ONp (biotin p-nitrophenyl ester ). Τα συνθετικά πεπτίδια P(13-39) και Ρ (65-97), που αντιστοιχούσαν στην Ν-CTR-I και C-TSR-I περιοχή της HARP μελετήθηκαν ως προς την επίδρασή τους στον πολλαπλασιασμό και στην μετανάστευση των καρκινικών κυττάρων του προστάτη (PC3).
Heparin affin regulatory peptide (HARP) is an 18 kDa growth factor that has a high affinity for heparin. HARP is highly conserved among species and shares 50% homology with Midkine and RI-HBP. The above proteins constitute a relatively new family of growth factors with high affinity for heparin. HARP has been originally purified from perinatal rat and bovine brain as a molecule that induces neurite outgrowth. HARP is also expressed in uterus, cartilage and bone extracts. Several reports have established a strong correlation between HARP expression and tumour growth and angiogenesis. HARP has been reported to be mitogenic for different types of endothelial cells and angiogenic in vivo and in vitro. HARP exerts its biological activity through interactions with cell surface proteoglycans, such as N-syndecan, or binding to more specific cell surface receptors. Receptor-type protein tyrosine-phosphatase β/ζ (RPTPβ/ζ) and its secreted variant phosphacan, as well as ALK are implicated in HARP signalling. The main target of this study is to investigate the structure and the biological activities of HARP, using smaller fragments of HARP which are biotinylated in order to study its further activities, the mechanisms and the interactions with the receptor. Biotin-labelled peptides are extremely useful tools for biochemistry, with applications in solid-phase immunoassays, affinity purification and receptor localization. The synthetic peptides of HARP were synthesized by Fmoc/t-Bu solid phase methodology utilizing a 2-chlorotrityl-chloride resin to provide a free NH2- amino-group and carboxyl acid, respectively. The simplest approach for the production of biotin-labelled peptides involves capping of a resin-bound free amino group with biotin, prior to cleavage of the peptide from the resin and side-chain deprotection. Because of the poor solubility of biotin in peptide synthesis solvents, biotin is most frequently introduced using a pre-formed active ester, such as biotin p-nitrophenyl ester. The synthetic peptides, P(13-39) and P(65-97) with amino acids sequence corresponding to the N- and C-TSR-I domains of HARP, were studied for their impact to the proliferation and chemotactic (migration) on prostate cancer cells (PC3).

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Διαμαντοπούλου, Ζωή. "Μελέτη του διαφορικού ρόλου των υποδοχέων RPTPβ/ζ και ALK στις βιολογικές δράσεις του αυξητικού παράγοντα HARP και πεπτιδίων του, σε κύτταρα καρκινικών σειρών προστάτη." Thesis, 2010. http://nemertes.lis.upatras.gr/jspui/handle/10889/4206.

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Η HARP (Heparin Affin Regulatory Peptide), γνωστή και ως πλειοτροπίνη, είναι ένας αυξητικός παράγοντας που η έκφρασή του στα ενήλικα άτομα είναι περιορισμένη σε συγκεκριμένους ιστούς. Ωστόσο, έκφραση ή υπερέκφρασή της έχει παρατηρηθεί in vivo σε διάφορους όγκους και στον ορό του αίματος ασθενών με διάφορες μορφές καρκίνου, καθώς και in vitro σε διάφορες καρκινικές κυτταρικές σειρές. Παρόλο που οι in vivo βιολογικές δράσεις της HARP είναι αδιαμφισβήτητες, δεν έχει διασαφηνιστεί ο μηχανισμός με τον οποίο ασκεί τις δράσεις αυτές. Επίσης, υπάρχουν πολλά αντικρουόμενα αποτελέσματα αναφορικά με τις in vitro βιολογικές της δράσεις. Στη συγκεκριμένη εργασία διερευνήθηκε το εάν η διαφορετική έκφραση των υποδοχέων της HARP, RPTPβ/ζ και ALK, είναι ένας άλλος λόγος για τα αντικρουόμενα αυτά αποτελέσματα. Χρησιμοποιώντας την RNAi τεχνολογία, δημιουργήσαμε DU145 και PC3 κύτταρα (κυτταρικές σειρές από καρκίνο ανθρώπινου προστάτη), τα οποία σταθερά έχουν μειωμένα επίπεδα έκφρασης του RPTPβ/ζ και του ALK. Τα DU145 κύτταρα εκφράζουν μόνο τον RPTPβ/ζ, σε αντίθεση με τα PC3 κύτταρα που εκφράζουν και τους δύο υποδοχείς. Τα αποτελέσματα έδειξαν ότι ο RPTPβ/ζ καταστέλλει την επαγόμενη από HARP κυτταρική προσκόλληση και μετανάστευση, ενώ ο ALK επάγει την επαγόμενη από HARP κυτταρική μετανάστευση. Επιπλέον, η μελέτη της μεταγωγής σήματος αυτών των υποδοχέων έδειξε ότι ο RPTPβ/ζ καταστέλλει τα επίπεδα φωσφορυλίωσης της κινάσης Src, της Fak, της Pten/Akt και των Erk1/2, ενώ ο ALK επάγει την ενεργότητα της Akt και των Erk1/2. Επιπρόσθετα, η μείωση της έκφρασης του RPTPβ/ζ σχετίζεται με την επαγωγή EMT φαινοτύπου, αφού καταστέλλει την έκφραση της E-καντερίνης και επάγει την έκφραση της Ν-καντερίνης, των ιντεγκρινών-α5, -αv και β3, καθώς και της MMP9. Επιπλέον, είναι γνωστό ότι οι αυξητικοί παράγοντες αποτελούν υπόστρωμα για διάφορα πρωτεολυτικά ένζυμα του κυτταρικού μικροπεριβάλλοντος, με αποτέλεσμα την παραγωγή βιολογικά ενεργών πεπτιδίων που μπορούν να έχουν παρόμοιες ή και αντίθετες δράσεις με το ολικό μόριο. Η πλασμίνη, η τρυψίνη και η MMP2, πέπτουν την HARP και παράγουν πεπτίδια που αναστέλλουν την επαγωγική της δράση. Σύμφωνα με αυτές τις μελέτες, το ενδιαφέρον για την ανακάλυψη πεπτιδίων με αντικαρκινική δράση εντοπίζεται στο καρβοξυτελικό τμήμα της HARP, καθώς και στις δύο κεντρικές περιοχές που παρουσιάζουν ομολογία με τις επαναλαμβανόμενες αλληλουχίες της θρομβοσπονδίνης-1. Στην παρούσα εργασία μελετήθηκε ο μηχανισμός δράσης του P(122-131) και οι βιολογικές δράσεις των P(13-39) και P(65-97). Τα αποτελέσματα έδειξαν ότι το P(122- 131) μετά την πρόσδεσή του στον RPTPβ/ζ, μειώνει τα επίπεδα φωσφορυλίωσης της κινάσης Src, της Fak, της Pten και των Erk1/2 και καταστέλλει την in vitro προσκόλληση και μετανάστευση των DU145 και LNCaP κυττάρων. Επιπλέον, τα αποτελέσματα υποστηρίζουν την υπόθεση ότι το P(122-131) καταστέλλει αυτές τις διαδικασίες και μετά από τον ανταγωνισμό του με τη HARP για την πρόσδεση όχι μόνο στον ALK, αλλά και σε άλλους υποδοχείς. Τέλος, χρησιμοποιώντας το σύστημα της χοριοαλλαντοϊδικής μεμβράνης εμβρύου όρνιθας, παρατηρήσαμε ότι το P(122-131) καταστέλλει και την in vivo αγγειογένεση. Παρόμοια με το P(122-131), τα P(13-39) και P(65-97) καταστέλλουν την in vitro προσκόλληση και μετανάστευση των DU145 και PC3 κυττάρων μετά την πρόσδεσή τους στον RPTPβ/ζ. Συμπερασματικά, στην παρούσα εργασία καταδεικνύεται ο ρόλος των υποδοχέων RPTPβ/ζ και ALK στον μηχανισμό δράσης του αυξητικού παράγοντα HARP και των πεπτιδίων του. Για πρώτη φορά αποδεικνύεται ότι η ανασυνδυασμένη HARP προκαρυωτικής προέλευσης είναι βιολογικά ενεργή και ότι η δράση της εξαρτάται από τη συνισταμένη των δράσεων που έχει κάθε υποδοχέας της, αντικατοπτρίζοντας τον περίπλοκο μηχανισμό δράσης της HARP και των πεπτιδίων της.
HARP (Heparin Affin Regulatory Peptide), also known as Pleiotrophin, is a growth factor that is thought to be involved in carcinogenesis. Elevated concentrations of this growth factor are found in many types of tumors, as well as in the plasma of patients with different types of cancer. However, contradictory results have been published concerning the in vitro activities of HARP. Here, we investigated whether the differential expression of HARP receptors, namely RPTPβ/ζ and ALK, is another reason for these controversies. Using the RNAi technology, we stably transformed prostate cancer cell lines DU145 and PC3 to knockdown RPTPβ/ζ or ALK expression. DU145 cells express only RPTPβ/ζ, while PC3 cells express both RPTPβ/ζ and ALK. Our results showed that RPTPβ/ζ inhibits HARP-mediated cellular adhesion and migration, while ALK induces HARP-mediated cellular migration. Investigation of the transduction mechanism revealed that RPTPβ/ζ inactivates Src, Fak, Pten/Akt, and Erk1/2, while ALK activates Akt and Erk1/2. In addition, RPTPβ/ζ knockdown promotes a shift in expression form E- to N-cadherin, and induces the expression of integrin-α5, -αv, -β3, and MMP9. Growth factors can be hydrolyzed by proteases, leading to the production of biological active peptides. Previous studies indicate that HARP is cleaved by enzymes in the extracellular environment, such as plasmin, trypsin, chymotrypsin, and MMP2. Moreover, the resulting peptides exert altered biological functions compared to the whole molecule. Here, we investigated the effect of (P122-131), corresponding to the basic cluster of the C-terminal region of HARP, as well as the effect of P(13-39) and P(65-97) derived from the TSR domains of HARP. Our results demonstrated that P(122-131) interacts with RPTPβ/ζ, inactivates its catalytic activity, and triggers a signal transduction pathway that inhibits DU145 and LNCaP adhesion and migration, while in parallel interferes with ALK or other pleiotrophin receptors inhibiting pleiotrophin-induced cellular adhesion and migration. In addition, P(122-131) inhibits angiogenesis in vivo, as determined by the chicken embryo CAM assay. Furthermore, P(13-39) and P(65-97) interacts with RPTPβ/ζ and inhibits DU145 and PC3 adhesion and migration. Taken together, the results of this study demonstrate the effect of RPTPβ/ζ and ALK on HARP and its peptides-mediated biological actions. Our results support the hypothesis that the overall effect of pleiotrophin depends on the expression profile of its receptors. Concluding, we show that bacterial pleiotrophin is biological active and part of the diversity of pleiotrophin biological actions is due to RPTPβ/ζ and /or ALK and the complex way of their interactions and signaling.

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46

Nascimento, Beatriz Alves do. "Relatórios de Estágio e Monografia intitulada “Medicamentos Órfãos – Perspetiva Regulamentar”." Master's thesis, 2021. http://hdl.handle.net/10316/99105.

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Abstract:

Relatório de Estágio do Mestrado Integrado em Ciências Farmacêuticas apresentado à Faculdade de Farmácia
Medicamentos órfãos e doenças raras são conceitos que ouvimos com regularidade no nosso quotidiano sem a lucidez dos escassos meios de prevenção, diagnóstico e tratamento que comprometem a qualidade de vida das pessoas portadoras destas doenças, bem como dos familiares que as rodeiam.De modo a fomentar a investigação, produção e comercialização de medicamentos órfãos cada vez mais são criadas políticas pela Agência Europeia do Medicamento (EMA), através do Comité dos Medicamentos Órfãos (COMP) e pelas autoridades regulamentares nacionais. Contudo, muitas necessidades ainda não são satisfatoriamente atendidas havendo um longo caminho a percorrer no futuro.Preparar um dossier de um medicamento órfão, escrevendo o documento técnico comum (CTD), difere de um medicamento tradicional desde logo devido ao baixo número de dados clínicos e experimentais existentes e ainda pela obrigatoriedade da presença da Secção 1.7 “Exclusividade de Mercado” no módulo 1 do CTD.O presente documento visa abordar as políticas vigentes na Europa para aprovação e comercialização de medicamentos órfãos, bem como os incentivos ao seu desenvolvimento. Dado a especificidade da Secção 1.7, contém ainda um exemplo ilustrativo da mesma, de modo a elucidar os pontos fulcrais a mencionar.O estágio curricular em Indústria Farmacêutica é uma das valências proporcionadas pela Faculdade de Farmácia da Universidade de Coimbra aos seus alunos, para que estes possam concluir o seu ciclo de estudos com o maior contacto com a realidade do mundo trabalho.O presente documento tem por objetivo analisar o meu estágio em Indústria Farmacêutica, no departamento de Assuntos Regulamentar na Bluepharma Indústria Farmacêutica S.A, através de uma análise SWOT demonstrado o meu percurso na empresa entre 11 de janeiro e 2 de abril 2021.O estágio curricular em Farmácia Comunitária é um complemento à formação do Mestrado Integrado em Ciências Farmacêuticas, de caracter obrigatório, que tem como objetivo complementar os conhecimentos apreendidos ao longo da formação académica.O presente documento tem por objetivo analisar o meu estágio em Farmácia Comunitária, na Farmácia Isabel Folhas, através de uma análise SWOT que descreve o decorrer do mesmo entre 5 de abril e 22 de julho 2021.
Orphan medicines and rare diseases are concepts that we hear regularly in our daily lives without the clarity of the scarce means of prevention, diagnosis and treatment that compromise the quality of life of people living with these diseases, as well as their families.In order to foster research, production and marketing of orphan medicinal products, policies are increasingly being developed by the European Medicines Agency (EMA), through the Committee for Orphan Medicinal Products (COMP) and national regulatory authorities. However, many needs are still not adequately met with a long way to go in the future.Preparing a dossier for an orphan medicinal product, writing the Common Technical Document (CTD), differs from a traditional medicinal product from the outset due to the low amount of existing clinical and experimental data and the mandatory presence of Section 1.7 "Market Exclusivity" in module 1 of the CTD.This document aims to address Europe’s policies for the approval and marketing of orphan medicinal products and incentives for their development. Given the specificity of Section 1.7, it also contains an illustrative example of this section in order to elucidate the key points to be mentioned.Internship in Pharmaceutical Industry is one of the opportunities offered by the Faculty of Pharmacy of the University of Coimbra to its students, so that they can complete their cycle of studies with the greatest contact with the reality of professional world.The following report aims to analyze my internship in Pharmaceutical Industry, in the Regulatory Affairs department at Bluepharma Indústria Farmacêutica S.A, through a SWOT analysis demonstrating my experience in the company between January 11 and April 2, 2021.The curricular internship in Community Pharmacy is a complement to the training of the Integrated Master in Pharmaceutical Sciences, of mandatory character that aims to complement the knowledge learned during its academic training.This document aims to analyze my internship in Community Pharmacy, at Isabel Folhas Pharmacy, through a SWOT analysis that describes the course of this journey between April 5 and July 22, 2021.

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47

Третьякова, Ольга Олександрівна. "Реінжиніринг діловодства та архівної справи в органах місцевого самоврядування." Магістерська робота, 2020. https://dspace.znu.edu.ua/jspui/handle/12345/5017.

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Третьякова О. О. Реінжиніринг діловодства та архівної справи в органах місцевого самоврядування : кваліфікаційна робота магістра спеціальності 281 "Публічне управління та адміністрування" / наук. керівник О. О. Широбокова. Запоріжжя : ЗНУ, 2020. 134 с.
UA : Мета дослідження: вивчення та окреслення особливостей реінжинірингу діловодства та архівної справи в органах місцевого самоврядування (на прикладі архівного управління Запорізької міської ради). Об’єкт дослідження: історія розвитку та еволюції діловодства і архівної справи в системі публічного управління та адміністрування за період історії незалежності України. Предмет дослідження: процес реінжинірингу діловодства та архівної справи в органах місцевого самоврядування. Методи дослідження: діалектичний, системний, аналіз і синтез, індукція і дедукція, порівняння, аналогія, моделювання. Гіпотеза: розробка єдиної (уніфікованої) системи електронного документообігу для реінжинірингу діловодства та архівної справи в системі органів місцевого самоврядування сучасної України, з урахуванням всіх існуючих вимог у нормативно-правовій базі діловодства та архівної справи. Висновки: 1. В Україні створено широку нормативно-правову базу з питань реінжинірингу діловодства та архівної справи. 2. З поширенням застосування новітніх інформаційних технологій розвиваються механізми взаємодії громадян з органами місцевого самоврядування. 3. Проводиться ґрунтовна робота, пов’язана із вдосконаленням систем електронного документообігу та запровадженням їх в практичну діяльність органів місцевого самоврядування. 4. Окреслено основні недоліки роботи систем електронного документообігу та запропоновано можливі варіанти їх вирішення.
EN : Research purpose is to study and outline the features of reengineering of paperwork and archival affairs in local self-government bodies (on the example of the archival department of Zaporizhzhia City Council). Research object is the history of paperwork and archival affairs’ development and evolution in the system of public management and administration during the history of Ukraine’s independence. Research subject is the process of paperwork and archival affairs’ reengineering in local self-government bodies. Research methods are dialectical, systemic, analysis and synthesis, induction and deduction, comparison, analogy, modeling. Research hypothesis is the development of a single (unified) electronic document flow system in order to reengineer the paperwork and archival affairs in local self-government bodies of modern Ukraine, taking into account all the existing requirements in the legal and regulatory framework of paperwork and archival affairs. Conclusions: 1. The broad legal and regulatory framework for reengineering of paperwork and archival affairs is created in Ukraine. 2. The mechanisms of citizens’ interaction with local self-government bodies are developing with the spread of the latest information technologies usage. 3. Thorough work concerning the improvement of electronic document flow systems and their introduction into the practical activity of local self-government bodies is carried out. 4. The main shortcomings of the electronic document flow systems are outlined and possible solutions are suggested.

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