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Junior, Edison Claudino Bicudo. "O circuito superior marginal: produção de medicamentos e o território brasileiro." Universidade de São Paulo, 2006. http://www.teses.usp.br/teses/disponiveis/8/8136/tde-17072007-104024/.
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O presente trabalho pretende explorar o conceito de circuito superior marginal, proposto por Milton Santos em 1975. Esse conceito faz referência a um subsistema econômico presente nas cidades dos países do Terceiro Mundo. Nesse subsistema, encontramos ações que são, a um só tempo, ligadas às lógicas da modernização e dotadas de menor conteúdo em técnica, ciência e informação. Com isso, formam-se ações híbridas, que expressam tanto as racionalidades globais, instrumentais, como as racionalidades locais, comunicacionais. Para a realização desse estudo, cuidamos da produção de medicamentos no território brasileiro. Embora atentando para as novas condições de hegemonia dos laboratórios multinacionais, enfatizamos a situação dos pequenos laboratórios. Estes se dedicam a produções menos complexas e empregam técnicas e informações menos sofisticadas. Além disso, ficam submetidos ao controle político que os agentes hegemônicos passam a realizar, sobretudo em função dos aparelhos normativos que regulam as ações no território. Nessa medida, os pequenos produtores de medicamentos conformam, para a atividade farmacêutica, um circuito superior marginal. Nosso estudo quer entender as integrações desse circuito com o meio construído em várias situações urbanas brasileiras.This work aims to explore the concept of marginal superior system, proposed by Milton Santos in 1975. This concept does reference to an economic subsystem that is presented in cities of Third World. In this subsystem we can find actions that are at the same time linked to the rationalities of the modernization and endowed with small contents in terms of technique, science, and information. Thus, hybrid actions emerge, expressing as global and instrumental rationalities as local and communicational rationalities. In order to develop this study, we are concerned about the production of medicines in the Brazilian territory. Though we consider the new conditions of hegemony from the multinational laboratories, we focused the situation of small laboratories. These latter ones develop less complex productions and employ less sophisticated techniques and information. Besides, they are submitted to the political control of the hegemonic actors, especially based on the normative tools that rule the actions in the territory. Thus, the small laboratories constitute, for the pharmaceutical activity, a marginal superior system. Our study aims to understand the linkages between this system and the built environment in several Brazilian urban situations.
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Van, Heerden Ilse. "Evaluation of a phytogenic product from two western herbal medicines to replace an antimicrobial growth promoter in poultry production." Thesis, University of Pretoria, 2010. http://hdl.handle.net/2263/28482.
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Antimicrobial growth promoters (AGPs) are substances that are added to feed in sub-therapeutic levels in intensive animal production to improve weight gain and conversion of feed (FCR) into body mass. AGPs have been used widely as growth promoters in broiler and pig production under high-density growth conditions. Despite the observed efficacy, the use of AGPs has been criticized due to its possible role in the development of antibiotic resistance in human pathogens. Directive 183/2003 of the European Parliament, issued in 2003, banned of the use of all antibiotic agents as growth promoters in the European Union from 2006. The new context caused an increase in the search for alternative growth promoters. The aim of this study was to produce a commercially viable prophylactic antibacterial phytogenic product from Ginkgo biloba and Hypericum perforatum with a low potential to develop resistance, as an alternative to AGPs in poultry production. The first objective of this study based on earlier results of the Phytomedicine Programme, was to evaluate the activity and potentize extracts from Ginkgo biloba and Hypericum perforatum for optimal activity against relevant bacterial pathogens. Extracts of ethyl acetate (EA), hexane, dichloromethane (DCM) and acetone (in order of activity) from a direct extraction procedure of powdered G. biloba leaves were active against Enterococcus faecalis, Staphylococcus aureus and Clostridium perfringens. The EA, hexane and DCM extracts were 2 to 3 times more active than the acetone extract (average total activity 1728 ml/g dry extract for the 3 pathogens). The DCM-, EA-, acetone- and hexane extracts (in order of activity) from the direct extraction procedure from H. perforatum were only active against C. perfringens with the first three extracts having a total activity of between 1026 and 1333 ml/g dry material and the hexane extract a total activity of 333 ml/g dry material. The spectrum of activity of G. biloba corresponds to that of Zn-bacitracin, which is commonly used an antibiotic growth promoter in the poultry industry. The second objective in this study was to combine extracts or fractions of extracts of G. biloba and H. perforatum to optimise activity against selected bacterial pathogens. A synergistic effect could be observed when combining a ratio of 1:5 of G. biloba: H. perforatum (hexane extracts) or 1:15 (acetone extracts) against E. faecalis while only an indifferent (neutral) effect was observed against C. perfringens. After elucidation of the quantitative and qualitative aspects involved in the antimicrobial activity, the major antibacterial compound from G. biloba was isolated and characterized as ginkgolic acid (C17:1). It was also determined whether activity against E. faecalis and C. perfringens in an extract or fraction of and extract of G. biloba can be attributed only to ginkgolic acid or whether synergism or other interactions also play a role in the antibacterial activity. It was shown that synergistic interactions are at play between constituents in the hexane and EA fraction, with the last mentioned fraction not containing any ginkgolic acid. These results support the use of the whole extract as opposed to isolated compounds as antimicrobial agents against pathogenic organisms. Two important pharmacodynamic parameters were investigated i.e. resistance development to a hexane extract and the isolated ginkgolic acid from G. biloba against E. faecalis and secondly the time-kill dynamics of this hexane extract over 24 h against E. faecalis. The bactericidal nature of the hexane extract from G. biloba as well the absence of decreased susceptibility to this extract (and the isolated ginkgolic acid) in the resistance studies against E. faecalis indicate that this extract has potential to be exploited as a alternative to AGPs in the poultry industry. The final objective was to determine the effect of extracts of G. biloba alone or in combination with H. perforatum extracts on the performance of broiler chickens over a 35 day period. The effect of these extracts on C. perfringens in the intestine of broilers was also investigated. No significant differences were found with relation to any of the production parameters studied (FCR, live weight or % survival) although a trend towards more favourable European Performance Efficiency Factor index values were observed for treatments containing G. biloba (5% improvement) or a combination of G. biloba and H. perforatum (2.1% improvement) compared to the untreated control. Similarly, Zn-Bacitracin resulted in a 5.5% improvement compared to the untreated control. There was a general trend (not statistically significant, P=0.05) towards a reduction in C. perfringens scores in the feed supplemented with G. biloba- in combination with H. perforatum extract which can probably be ascribed to the direct antimicrobial effect. The rate of colonization was however too low to cause infection probably due to lack of virulence of the C. perfringens challenge and the absence of predisposing factors due to the hygienic growth conditions used. It is necessary for an effective disease model to be developed in order for the efficacy of any new treatment method to be properly evaluated. Such a model will require a much higher incidence of disease and reproducibility than was achieved in this project. The safety of using extracts of G. biloba with ginkgolic acid as the prime antibacterial compound was considered. The active dose was at least 42 times lower than safe dosage recommended in the literature. The combination of extracts of G. biloba and H. perforatum holds promise as a potential growth promoter in poultry production. Better results may be achieved if potentized extracts are used and compared with Zn-Bacitracin and a negative control under industrial growth conditions where the birds are stressed and natural infections would take place. CopyrightThesis (PhD)--University of Pretoria, 2009.
Paraclinical Sciences
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Beaney, Alison M. "The development and implementation of appropriate standards for the preparation and production of medicines." Thesis, University of Sunderland, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.514221.
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PUPILLO, Gaia. "Radioisotopes production via accelerator for nuclear medicine applications." Doctoral thesis, Università degli studi di Ferrara, 2014. http://hdl.handle.net/11392/2388938.
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SORTE, JUNIOR Waldemiro Francisco. "The Role of Governmental Policies in Nurturing the Pharmaceutical Industry in Brazil: The Mix of Centralized Procurement, Public Drug Production and Public-private Partnerships." 名古屋大学大学院国際開発研究科, 2012. http://hdl.handle.net/2237/16249.
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Böttcher, Malin, Jenny Fredriksson, Anna Hellquist, and Maria Jenmalm. "Effects of breast milk from allergic and non-allergic mothers on mitogen- and allergen-induced cytokine production." Linköpings universitet, Pediatrik, 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-26400.
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Breast milk contains several components that provide specific immunity and affect the maturation of the infant's immune system. The aim of this study was to analyze the effects of breast milk, on mitogen- and allergen-induced cytokine production from cord blood mononuclear cells (CBMC), and if those effects differ between allergic and non-allergic mothers. The cells were incubated for 96 h with phytohemagglutinin (PHA), ovalbumin or cat dander in the presence of various dilutions of colostrum. Colostrum inhibited both mitogen- and cat-induced IFN-γ and mitogen-induced interleukin-4 (IL-4) production. The inhibition on IFN-γ production was to some extent caused by TGF-β, as the effect was modified when an anti-TGF-β antibody was added to the cultures. In contrast, colostrum enhanced allergen-induced production of the Th2-like cytokines IL-5 and IL-13, and this was accompanied with increased production of IL-10. No differences were found between allergic and non-allergic mothers. The inhibitory effect of breast milk on IFN-γ production, which was partly due to the high levels of TGF-β, together with the enhancing effect on IL-10 secretion, confirm that breast milk is anti-inflammatory. Although the production of IL-5 and IL-13 was enhanced by colostrum, this was accompanied with an increased production of IL-10. Together with the high levels of TGF-β in breast milk and inhibitory effect of colostrum on IL-4 production, this suggests a possible mechanism whereby breast-feeding may protect against the development of allergy. Despite differences in the composition of breast milk between allergic and non-allergic mothers, the effects of breast milk on cytokine production from CBMC were independent of the atopic status of the mothers.
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Abell, Kaitlynn M. "Predictive analytics and data management in beef cattle production medicine." Diss., Kansas State University, 2017. http://hdl.handle.net/2097/35418.
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Doctor of PhilosophyDepartment of Diagnostic Medicine/Pathobiology
Robert L. Larson
Bradley J. White
Utilization of data analytics allows for rapid and real-time decision making in the food animal production industry. The objective of my research was to implement and utilize different data analytic strategies in multiple sectors of the beef cattle industry in order to determine management, health, and performance strategies. A retrospective analysis using reproductive and genomic records demonstrated that a bull will sire a larger number of calves in a multiple sire-pasture compared to other bulls in the same pasture. A further study was performed to determine if behavior differences existed among bulls in a multiple-sire pasture, and the ability of accelerometers to predict breeding behaviors. Machine learning techniques used classifiers on accelerometer data to predict behavior events lying, standing, walking, and mounting. The classifiers were able to accurately predict lying and standing, but walking and mounting resulted in a lower predictable accuracy due to the extremely low prevalence of these behaviors. Finally, a new form of meta-analysis to the veterinary literature, a mixed treatment comparison, was able to accurately identify differences in metaphylactic antimicrobials on outcomes of bovine respiratory disease morbidity, mortality, and retreatment morbidity. The meta-analysis was not successful in determining the effects of metaphylactic antimicrobials on performance outcomes.
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MARTINI, Petra. "High-Yield Cyclotron Production of Metallic Radioisotopes for Nuclear Medicine." Doctoral thesis, Università degli studi di Ferrara, 2018. http://hdl.handle.net/11392/2487885.
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The main purpose of LARAMED project (LAboratoty of Radioisotopes for MEDicine), founded at LNL-INFN, is the R&D on cyclotron production of conventional, such as Tc-99m (TECHN-OSP projects), and emerging, such as Cu-67 (COME project), metallic medical radioisotopes. The aim of my PhD has been the development, optimization and automation of post-irradiation target processing systems, enabling to recover in high yield highly pure radioisotopes (RI), one of the most critical steps in the RI cyclotron production.
The possibility of a reactor-produced molybdenum-99 shortage, used as parent nuclide of in 99Mo/99m Tc generators, is still a potential scenario. The direct cyclotron-production of Tc-99m through the (p,2n) reaction on a Mo-100 target seemed to be a reliable solution. In the framework of TECHN-OSP project, a technology for enabling the in-hospital cyclotron self-production of Tc-99m, in order to afford the availability of the most used radiometal in diagnostic applications in case of shortages, has been developed. The Tc-99m cyclotron-production optimization included the design of a solid target, the development of an automatic module for target processing and enriched target material recovery study. In this thesis, the description of Tc-99m production experiments, performed in collaboration with the Sant’Orsola Hospital in Bologna, and the development of the automatic module for target processing, are well detailed.
During my PhD I had the opportunity to collaborate with the Canadian research group at TRIUMF (Vancouver, CA), also working on Tc-99m cyclotron-production, by contributing at the optimization and automation of molybdenum target dissolution and purification procedure of cyclotron-produced Tc-99m. In this thesis a comparison between the two developed, Italian and Canadian, target processing setup is also reported.
Alongside that, I have collaborated to COME project whose purpose is the evaluation of the cyclotron production efficiency of Cu-67, a particularly interesting RI for its application in “theranostics”. The large scale cyclotron-production of this RI is still a poorly studied key point. In order to define the Cu-67 best cyclotron-production route, we focused our attention on unknown cross-section measurement of nuclear reactions on a Zn-70 target (35-70MeV energy range). Essential for this project was the development and optimization of a high yield separation and purification procedure of Cu-67 from the Zn-70 bulk and the co-produced Ga-67 contaminant that, having the same γ-lines of Cu-67 (both decay to Zn-67 with similar half-lives), poses a serious issue for the determination of the activity of Cu-67. The description of the experiments, performed in collaboration with ARRONAX, is reported in this thesis.
Finally, the clinical needs of larger amount of the PET radiometal generator-produced Ga-68 prompted TRIUMF Life Sciences division to investigate Ga-68 cyclotron-production from liquid target since it is based on the existing medical-cyclotron network and technology. This technique will improve the availability of Ga-68 in hospitals housing an appropriate cyclotron by making them independent self-producers. Since the major problem affecting liquid targets is the contamination with radioactive/stable metals (e.g. iron) coming from the dissolution of some material from vacuum isolation or target body components during the irradiation, a separation and purification procedure together with a semi-automatic system, particularly focused on the purification of Ga-68 from Zn and Fe, have been developed. The main purpose is to obtain a final product suitable for medical use and to enable radiolabeling and in-vivo imaging studies with cyclotron produced 68Ga-DOTATOC.Il progetto LARAMED (LAboratoty of Radioisotopes for MEDicine), fondato presso i LNL-INFN, ha come scopo l’R&D per la produzione da ciclotrone di radioisotopi metallici convenzionali, come il Tc-99m (progetto TECHN-OSP, ed emergenti, come il Cu-67 (progetto COME), per uso medicale. L'obiettivo del mio dottorato di ricerca è stato lo sviluppo, ottimizzazione e automazione di sistemi di processamento dei target irraggiati al fine di estrarre, in alta resa e purezza, il radioisotopo (RI) di interesse, uno dei passaggi più critici nella produzione da ciclotrone dei RI per la medicina. La possibilità di un’ulteriore crisi di produzione da reattori nucleari di Mo-99, nuclide genitore nei generatori Mo-99/Tc-99m, è ancora uno scenario possibile. La produzione diretta di Tc-99m da ciclotrone per mezzo della reazione nucleare Mo-100(p,2n) sembra essere una soluzione alternativa affidabile. Nell’ambito del progetto TECHN-OSP è stata sviluppata una tecnologia in grado di rendere le radiofarmacie delle Medicine Nucleari, che ospitano un ciclotrone appropriato, indipendenti nella produzione di Tc-99m al fine di sopperire ad ogni eventuale carenza nell’approvvigionamento dei generatori. L’ottimizzazione della produzione ha previsto la progettazione di un target, lo sviluppo di un modulo automatico per il processamento del target e lo studio del recupero del materiale arricchito costituente il target stesso. In questa tesi sono descritti i test di produzione di Tc-99m, eseguiti in collaborazione con l'ospedale Sant'Orsola di Bologna, ed in particolare lo sviluppo di un modulo automatico di processamento del target. Nel corso del dottorato, ho avuto l'opportunità di collaborare con il gruppo di ricerca canadese al TRIUMF (Vancouver, CA), anch’esso coinvolto nell’ottimizzazione della produzione di Tc-99m da ciclotrone, contribuendo all'ottimizzazione e automazione delle procedure di dissoluzione e purificazione di Tc-99m da target di Mo-100. In questa tesi viene anche riportato un confronto tra i due sistemi di processamento target da me sviluppati, in Italia e in Canada. Parallelamente ho collaborato al progetto COME il cui obiettivo risiede nella valutazione dell'efficienza di produzione di Cu-67 da ciclotrone, RI particolarmente interessante per le sue applicazioni in “teranostica”. La produzione da ciclotrone su larga scala di questo RI è ancora un punto chiave scarsamente studiato. Al fine di definire la migliore via di produzione di Cu-67, abbiamo focalizzato l’attenzione su misure di sezioni d’urto inedite (target Zn-70, protoni incidenti di energie 35-70MeV). Essenziale per questo progetto è stato lo sviluppo di un processo altamente efficiente di separazione di Cu-67 dal target e dal Ga-67, coprodotto che, avendo le stesse linee γ del Cu-67, crea problemi nella determinazione dell'attività di Cu-67. La descrizione degli esperimenti, eseguita in collaborazione con ARRONAX, è riportata in questa tesi. Infine, le esigenze cliniche di una maggiore quantità di Ga-68, RI PET attualmente prodotto da generatore Ge-68/Ga-68, hanno spinto il gruppo di ricerca del TRIUMF a studiare la produzione di Ga-68 da ciclotrone a partire da un target liquido di Zn-68, al fine di migliorare la disponibilità di Ga-68 negli ospedali che ospitano un ciclotrone appropriato rendendoli produttori indipendenti. Poiché il problema principale che colpisce la produzione da target liquido è la contaminazione da metalli (es. Fe) provenienti dalla degradazione di alcuni componenti del corpo del target, è stata sviluppata una procedura di separazione e purificazione del Ga-68 da Zn e Fe. Lo scopo principale è quello di ottenere un prodotto finale adatto all’uso medico e di consentire la radio-marcatura di (Ga-68)-DOTATOC e studi di imaging in vivo con Ga-68 prodotto da ciclotrone.
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Robson, Jo. "Neologism production in jargon aphasia." Thesis, City, University of London, 1998. http://openaccess.city.ac.uk/17418/.
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This study investigates a jargon speaker, LT, whose connected speech is composed almost entirely of neologisms. Despite the general intelligibility of his speech, LT is able to produce discrete responses in picture naming tasks. Neologisms were investigated for their phonemic content. Non word responses maintained the normal English distribution of phonemes. Importantly, they also showed greater than chance levels of target relatedness. Analysis of LT's responses to a set of stimuli controlled for their consonant content allowed more detailed investigation of the nature of target and error phonology. A strong influence of phoneme frequency was identified. Higher frequency consonants showed a pattern of frequent but rather indiscriminate use. They often appeared in target related contexts but were also frequently misused in contexts where they were not required by the target phonology. Lower frequency consonants were realised less often. However, their use was restricted to target related contexts and they seldom appeared as error phonology. Further investigation showed that LT's ability to realise target phonology was influenced by the nature of the output task. A semantically primed reading condition resulted in a significant increase in the number of correct responses. Neologistic output showed a significant increase in the ability to realise target phonemes. Patterns of individual consonant use also showed significant changes. High frequency consonants showed a more refined distribution, appearing less frequently as error phonology. Low frequency consonants increased their rate of use but continued to be restricted to target related contexts. The findings of the investigations are discussed. The results are best explained by theories of neologism production which maintain a direct relationship between target and neologistic phonology and which propose a single mechanism underlying the production of both target related and abstruse neologistic output. Interactive activation accounts of lexical processing appear to be well placed to explain LT's output and a preliminary account is offered. Recommendations for the future investigation of neologistic output are made.
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Field, Helen. "On production of recombinant immunoglobulin variable domains." Thesis, University of Oxford, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.330288.
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Demontrond, Isabelle. "Production of antibodies for cell surface antigens." Thesis, University of Southampton, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.316348.
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Reece, Thomas Ray. "Public health and swine production medicine aspects of vH1N1 influenza virus." Kansas State University, 2012. http://hdl.handle.net/2097/13807.
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Master of Public HealthDepartment of Diagnostic Medicine and Pathobiology
Robert L. Larson
Variant H1N1 influenza (vH1N1) virus is an issue both in swine production medicine and in the arena of public health. Influenza viruses can infect but not always produce disease in avian, humans and swine. Swine are unique among the three previously mentioned species in that their respiratory epithelium possesses three receptor sites for the virus types common to each of the three mentioned species. Swine influenza virus (SI) is common and widespread in nearly all Midwestern swine herds and can be transmitted by both direct contact and aerosolization. All of the three previously mentioned species have the potential to re-assort (produce virons containing genetic material of different virons to produce a unique influenza virus (IV). Because of their three specific receptor sites, swine have the greatest re-assortment capability. This re-assortment has the potential is a low mortality/high morbidity disease that is a substantial cost to the swine industry due to its negative effect on production parameters such as average daily gain (ADG) and feed efficiency (FE). It is a public health concern due to its potential to produce different virus types which may have increased mortality/morbidity in humans. Avian are the IV reservoir and have the ability to introduce virus types that are foreign to specific populations in all venues on the planet. It is in the mutual best interest of public health and swine production to mitigate the introduction of different virus types in swine and to control existing infections in swine populations with a goal of establishing SI-free herds. Mitigation for swine populations can occur through vaccination, diagnosis/isolation, and Biosecurity procedures designed to reduce/eliminate IV introduction into swine production facilities. In addition, preventing the interaction of infected humans with swine is another component of swine population Biosecurity.
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Menezes, Nayra Karinne Bernardes de. "Uma análise sobre aquisição e criação de conhecimento na produção de fármacos similares." Universidade do Vale do Rio dos Sinos, 2010. http://www.repositorio.jesuita.org.br/handle/UNISINOS/3541.
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Este estudo objetiva em analisar: Como Adquirir e Criar o Conhecimento para o Processo de Produção de Fármacos Similares que perderam patente. Tem como intuito, de contribuir sobre a discussão da relação entre imitação e inovação no processo de produção. Medicamentos sem patente têm competido com base em preços, ao invés de inovação. Considerando que a competição não é baseada em inovações, recursos e conhecimento são necessários para melhorar o processo de produção destes medicamentos, como um caminho para obter um equilíbrio entre preço e qualidade. Este estudo investiga habilidades estratégicas específicas e diferentes conhecimentos que tem sido usado em casos particulares. Informações empíricas foram levantadas em laboratórios situados no Distrito Agroindustrial de Anápolis (DAIA, Brasil), que é o grupo principal de indústrias dedicadas à produção de medicamentos que estão fora da lei de patentes da América Latina. Os dados foram coletados após várias entrevistas, análises de documentos e observação direta. As evidências mostram que os conhecimentos científicos e tecnológicos têm melhorado a produção de tais medicamentos. Esse melhoramento depende de recursos internos dos laboratórios, assim como, fontes externas de Institutos de Pesquisas e Universidades. Finalmente, o estudo sugere que todo o processo necessário para imitar as fórmulas de medicamentos que ganharam domínio público, contribui para construir capabilities relacionadas à inovação.
This study intends to analyse how to acquire and create knowledge to improve the production process of medicines which are out of patent protection rules. It intends to contribute to the discussion about relations between imitation and innovation in industrial production. Medicines which are out of patent rules have been competing on a basis of price rather than on innovation. However, considering that even if competition is not based on innovation, knowledge resources are needed to improve the production processes of these medicines as a way to achieve an optimal balance between price and quality. This study investigates the specific strategic skills and kinds of knowledge that have been used in this particular case. Empirical data was obtained from labs situated at Anapolis District (DAIA, Brasil), which is the main cluster of industries dedicated to the production of medicines that are out of patent rules in Latin America. Data was collected through interviews, documents analysis and direct observation. The evidences show that scientific and technological knowledge have been improved on the production of these medicines. This improvement depends on internal resources of the lab as well on the interaction with external sources as research institutes and Universities. Finally, the study suggests that all the processes required to imitate dominated formulas of medicines which are out of patent rules contribute to build capabilities related to innovation.
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Daghman, Nureddin A. "A study of the factors regulating erythropoietin production." Thesis, Queen's University Belfast, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.337043.
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Wai, Wing-yin Eric. "Effect of herbal medicine (Ganoderma lucidum) on nitric oxide production in macrophages." Click to view the E-thesis via HKUTO, 2003. http://sunzi.lib.hku.hk/hkuto/record/B3197126X.
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Basford, Christina Louise. "Production of stem cell populations from umbilical cord blood for regenerative medicine." Thesis, University of Newcastle Upon Tyne, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.519640.
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衛穎賢 and Wing-yin Eric Wai. "Effect of herbal medicine (Ganoderma lucidum) on nitric oxide production in macrophages." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2003. http://hub.hku.hk/bib/B3197126X.
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Edialla, figueiredo zaire Carla. "L’introduction des traitements antirétroviraux de 3ème ligne au Brésil : Contexte, Modalités, Enjeux, Perspectives." Thesis, Sorbonne Paris Cité, 2018. http://www.theses.fr/2018USPCD073.
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Si de nombreux travaux ont été consacrés à la politique menée au Brésil dans la lutte contre la pandémie du Sida, très peu en revanche prennent pour objet central ses développements les plus récents qui consistent en l’introduction d’une 3ème ligne d’antirétroviraux pour les patients qui en ont besoin. L’introduction d’une troisième ligne soulève des problèmes complexes et pour parte inédits. Quel mode de sélection des patients, comment les déclarer éligibles ? Quel mode d’administration et de suivi ? Comment l’hôpital s’organise-t-il ? Est-il préparé pour faire face à cette tache inédite ? Est-il toujours en situation de la faire de manière efficace ? Enfin last but not least comment assurer le surcoût de financement que représente l’acquisition de la 3ème ligne dont les prix sur le marché mondial sont prohibitifs et sans rapports avec les prix des antirétroviraux de première et même de seconde ligne. Des politiques locales de production (sous licence) de tels médicaments sont-elles possibles ? À quelles conditions ? Telles sont les questions au centre de cette thèse. Pour tenter d’y réponde, la thèse est organisée en deux parties : la première présente les caractéristiques de l’épidémie et le contexte institutionnel de sa prise en charge ; la deuxième retrace et analyse les conditions de l’introduction d’une 3ème ligne de traitement antirétroviral au Brésil. La pérennité du programme brésilien est confrontée à plusieurs défis. Tout d’abord, (i) l’arrivée de nouveaux patients qui commencent un traitement chaque année. Le traitement offrant une espérance de vie plus longue, (ii) les patients restent inscrits dans le programme plus longtemps. Enfin, pendant cette période, les patients restent plus vulnérables aux mutations virologiques, (iii) ce qui exige un changement de thérapie. L'analyse du cas brésilien montre que la nécessité croissante d'intégrer de nouveaux traitements dans les protocoles nationaux représente une charge très lourde pour le budget du programme de lutte contre le Sida. Ainsi en 2014, l’achat des médicaments de 3ème ligne représentaient-ils 34,88% du coût total d’achat des antirétroviraux. Entre 2010 et 2014, ces médicaments ont eu aussi une forte influence sur la croissance du coût total des antirétroviraux. Aussi pour tenter de surmonter les obstacles qui se dressent dans l’accès aux médicaments contre le VIH, le Brésil s’est-il engagé dans une politique de production nationale à travers le Partenariat de Développement Productif (PDP), et encourage-t-il de plus en plus l’industrie brésilienne à s’engager dans la production d’antirétroviraux. Enfin en se tournant du côté de la demande ce travail donne un aperçu de la situation des patients brésiliens assistés par l’hôpital public. Une étude de cas met en évidence qu’avant de faire face au VIH, les patients doivent surmonter d’autres défis tels que l’instabilité financière et le manque de scolarité qui mène à la méconnaissance de ses droits. Ce cadre ne permet pas de produire les résultats d’observance souhaités : seulement 20,7% des 145 patients ont une bonne observance. Des politiques de soins tournées vers les patients de 2ème et 3ème lignes sont donc indispensables pour éviter et prévenir les changements de thérapies en lien à une observance inadéquateThe continuity of the Brazilian HIV / AIDS program faces several challenges: first, it is necessary to count the annual arrival of new patients. Next, we show that the program increases life expectancy and thus patients spend more time in the program. Finally, it should be noted that during the long treatment period, patients are vulnerable to viral mutations, which requires a change in therapeutic treatment. The analysis of the Brazilian case shows that the increasing need to integrate new drugs into therapeutic protocols makes it difficult to budget for patented antiretrovirals. In 2014, expenditures with 3rd line antiretrovirals reached 34.88% of the total antiretroviral budget and served only 3.8% of Brazilian patients in the same year. Brazil admits that investing in innovation is important in order to overcome barriers to access to medicines. In this way, the country imposes its national production policy through the Partnership for Productive Development (PPD) program, intensifying support to the Brazilian industry for the manufacture of medicines. We present a case study of the situation of Brazilian patients treated in a public hospital. According to data from the pharmacy, only 20.7% of the 145 patients have good therapeutic adherence. The Brazilian health system and the protocols to fight HIV suppose the integrality of the health care, that is to say that all the needs for the recovery of the state of health must be filled. The establishment of specific care policies for 2nd and 3rd line patients is imperative to avoid and prevent changes in therapies related to inadequate therapeutic adherence
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Malkani, Olaniran Angeli Krishin. "The response to, and production of cytokines in psoriasis." Thesis, Imperial College London, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.364354.
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McKnight, Andrew John. "The repertoire of lymphokine production by T cell subpopulations." Thesis, University of Oxford, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.291402.
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Thompson, K. M. "The production of human monoclonal antibodies from autoimmune patients." Thesis, University of Bath, 1986. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.356846.
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Alsalem, Jawaher Abdullah. "Vitamin D3 production by ocular barrier epithelial cells." Thesis, University of Birmingham, 2013. http://etheses.bham.ac.uk//id/eprint/4243/.
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Extra-renal synthesis of vitamin D3 has been reported in many tissues and cells including barrier sites where it induced immunomodulatory effects. I investigated local synthesis of vitamin D3 and its role in the induction of host defense peptides (HDPs) in human ocular barrier epithelial cells. I also examined the association between vitamin D receptor (VDR) single nucleotide polymorphism (SNP) with intermediate uveitis (IU) in Caucasians. Human corneal endothelial (HCEC-12), non-pigmented ciliary body epithelial (ODM-2), and adult retinal pigment epithelial (ARPE-19) cell lines, expressed mRNA and protein for VDR and vitamin D3 pathway elements and can locally synthesise 1,25(OH)2D3 in vitro. These cells upregulated mRNA, but not protein expression of HDPs in response to vitamin D3. IL-1β and TNF-\(\alpha\) did not synergise with vitamin D3 to upregulate HDPs in ocular barrier epithelial cells. VDR single nucleotide polymorphisms BsmI (rs1544410) is significantly associated with IU. Allele rs1544410-T and genotype rs1544410-CT were higher in IU patients than healthy controls. The results show that that extra-renal production of active vitamin D3 occurs in ocular barrier cells and may contribute to immune regulation in the eye. The association with SNP in the vitamin D3 receptor gene and intermediate uveitis suggests that genetic control of vitamin D3 may be linked to ocular inflammatory disease.
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Kirkemo, Fredrik Motland. "Adam Lonicer's Kreuterbuch and 16th century distillation : An experimental approach to the study of Adam Lonicer and some of the technology applied by him and his contemporaries in the production of medicines." Thesis, Norges teknisk-naturvitenskapelige universitet, Institutt for kjemi, 2014. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-24590.
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The Kreuterbuch published by Adam Lonicer (1528--1586) in 1569 experienced immense popularity in the 16th century. The book is a lavishly illustrated herbal, in which distillation is a central theme. It has formed the basis for a full-scale reconstruction of distillation processes from the 16th century. With the aid of specialized craftsmen and -women from the University's workshop a furnace, equipment and glassware needed to reproduce the distillation techniques of the Renaissance were reconstructed. The ultimate goal of the reconstruction was both to investigate the equipment and techniques' efficiency with some modern methods, and to explore the synergetic effect of working with texts in parallel with the actual reconstruction. The methodology of reconstructing historical equipment and experiments in alchemy and chemistry has showed promise in several studies in history of science (Holmes and Levere, 2002), but as Martinón-Torres (2011) has pointed out, there is "a slant in practice-oriented studies towards the metallurgical aspects of alchemy that leaves much room for research on the practical aspects of iatrochemistry". The analyses of the reconstructed equipment shows that some of the hypotheses concerning the evolution of distillation technology should be revised.The thesis has been a part of the interdisciplinary Mubil (Museum and Library -- a digital laboratory) project.
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Wang, Ling, and Shunbin Ning. ""Toll-Free" Pathways for Production of Type I Interferons." Digital Commons @ East Tennessee State University, 2017. https://dc.etsu.edu/etsu-works/6540.
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Pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) are recognized by different cellular pathogen recognition receptors (PRRs), which are expressed on cell membrane or in the cytoplasm of cells of the innate immune system. Nucleic acids derived from pathogens or from certain cellular conditions represent a large category of PAMPs/DAMPs that trigger production of type I interferons (IFN-I) in addition to pro-inflammatory cytokines, by specifically binding to intracellular Toll-like receptors or cytosolic receptors. These cytosolic receptors, which are not related to TLRs and we call them "Toll-free" receptors, include the RNA-sensing RIG-I like receptors (RLRs), the DNA-sensing HIN200 family, and cGAS, amongst others. Viruses have evolved myriad strategies to evoke both host cellular and viral factors to evade IFN-I-mediated innate immune responses, to facilitate their infection, replication, and establishment of latency. This review outlines these "Toll-free" innate immune pathways and recent updates on their regulation, with focus on cellular and viral factors with enzyme activities.
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Cano, Garrido Olivia. "Production of protein nanomaterials in lactic acid bacteria for human and animal medicine." Doctoral thesis, Universitat Autònoma de Barcelona, 2016. http://hdl.handle.net/10803/392682.
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Tot i que Escherichia coli és el bacteri més àmpliament usat en el camp de la producció de proteïnes recombinants, aquest conté lipopolisacàrids (LPS) en la seva membrana externa. Com a conseqüència de la presència d’aquest contaminant bacterià, el potencial dels productes proteics produïts amb finalitats mèdiques en aquest microorganisme Gram-negatiu es veu severament limitat. En aquest context, els bacteris de l’àcid làctic (BAL), un grup de microorganismes Gram-positius, han anat guanyant importància com a alternativa per la producció de proteïnes recombinants segures. Els BAL, que no contenen endotoxines, són àmpliament reconeguts pel seu ús en la indústria alimentària, i a més a més, han estat classificats com organismes “Generally Recognized As Safe” (GRAS) per part de les agències reguladores. Tanmateix, durant les últimes dècades, diverses eines han estat desenvolupades per millor els sistemes d’expressió proteics GRAS, amb l’objectiu de sintetitzar proteïnes heteròlogues lliures de toxines , la majoria d’aquetes utilitzant el bacteri Lactococcus lactis.
Les proteïnes recombinants solubles s’associen normalment a una elevada inestabilitat i a alts costos associats als processos de producció i purificació, esdevenint econòmicament inviables pel desenvolupament de productes comercials basats en proteïnes per medicina humana i, molt especialment, per medicina animal. Contràriament, l’ús de proteïnes heteròlogues en forma de nanopartícules amiloides biològicament actives, s’ha presentat com una alternativa rentable i estable. Estudis recents evidencien l’enorme potencial d’aquestes nanopartícules proteiques en l’àmbit de la nanomedicina. No obstant, tot i el seu potencial, aquestes nanopartícules han estat bàsicament produïdes en E.coli i, fins al moment, la seva producció no ha estat explorada en BAL. A més a més, la seva ultraestructura no s’ha estudiat en detall, essent una important tasca que encara queda per resoldre.
Així doncs, en aquest estudi, hem descrit l’organització supramolecular d’aquestes nanopartícules composades alhora per proteïnes en estat amiloide i natiu. D’altra banda, hem dut a terme el desenvolupament d’una metodologia per tal de produir materials proteics econòmics, segurs i funcionals mitjançant una plataforma de producció lliure de LPS. Concretament, s’ha utilitzat L. Lactis per tal de produir aquestes nanoestructures proteiques recombinants amb rellevància en medicina humana i animal.
Així mateix, s’han determinat també les propietats fisicoquímiques d’aquestes nanopartícules fent ús d’una amplia varietat de tècniques. A grans trets, degut a característiques com la seva activitat biològica, estabilitat, versatilitat i seguretat, aquestes nanopartícules proteiques esdevenen un material prometedor per finalitats terapèutiques.Despite Escherichia coli is the workhouse for recombinant protein production purposes, this bacterial species contains lipopolysaccharide (LPS) in its outer membrane. Consequently, the presence of bacterial endotoxic contaminants severely restricts the potential medical applications of protein goods produced in this Gram-negative microorganism. In this context, lactic acid bacteria (LAB), a group of Gram-positive microorganisms, has been gaining momentum as an alternative for the production of safe recombinant proteins. LAB, which lack endotoxins, are widely well-known by their use in the food industry and are generally recognized as safe (GRAS) organisms by regulatory agencies. Interestingly, during the last decades, many tools have been developed using these food-grade expression systems with the aim to synthesise heterologous proteins, most of them being developed in Lactococcus lactis. Recombinant soluble proteins are often associated to instability and high production and purification costs, being not economically viable for the development of protein-based commercial products for human, but specially, for animal medicine. In this regard, the use of heterologous proteins in form of biologically active amyloidal nanoparticles has been shown to be a cost-effective and stable alternative. Concomitantly, recent studies evidence the enormous potential of these protein-based nanoparticles in nanomedicine. Nevertheless, despite its potential, protein nanoparticles have essentially been produced in E. coli and they have never been described as LAB products. Besides, their ultrastructure has not been studied in detail, remaining as an unsolved task. Thus, in the present study, we have further described the supramolecular organization of these protein nanoparticles composed by both amyloid-like and native-like proteins. On the other side, we have developed a methodology to produce inexpensive, safe, and functional protein-based materials in a LPS-free production platform. Specially, we have used L. lactis to produce nanostructured recombinant proteins relevant for human and animal medicine. Besides, we have also determined the physico-chemical properties of such nanoparticles using a wide variety of techniques. Altogether, the biological functionality, stability, safety, and te versatility of the platform, make these protein-only nanoparticles a very promising material for therapeutic purposes.
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Wainer, Rafael. "When medicine cannot cure : dying children, palliative care, and the production of companionship." Thesis, University of British Columbia, 2008. http://hdl.handle.net/2429/1597.
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Although the curative model of medical care is predominant it is necessary to consider the palliative strategies at the end-of-life. The inter-relation of dying children, their families and pediatric palliative care teams are seldom analyzed outside Palliative Care. However, it is important to ethnographically think about the disturbing experiences of body and subject disintegration while people are directly experiencing them, even when the person is a child or a newborn baby. A central topic in this study is how personhood, body formation and disintegration, and childhood can be understood within the context of unevenly constructed and shared palliative communication with and without words. Hence, I analyze in this study how a Palliative Care Team in the city of Buenos Aires provides care, communicates, and ultimately produces a particular companionship to dying children and their families. This work is built on qualitative information gathered and produced during my four-month fieldwork with the Palliative Care Team. The ethnographic techniques (participant observation, non-participant observation and open-ended semi-structured interviews) I conducted show that their strategies of care and communication have as the main goal the process of companionship at the end of children’s lives. It is necessary to understand how patients, parents, and other family members are situated in this field of tensions between restorative and palliative medicine, and brought into this culture of Palliative Care in a public children’s hospital. My research asks, in what ways are pediatric Palliative Care practices exclusive to the social and cultural contexts of Buenos Aires? This work has three main sections: 1. care, 2. communication, and 3. companionship. In section one I focus on the clinical and non-clinical aspects of care involving the professionals’ and volunteers’ practices of giving care. In section two I concentrate my attention on the verbal and non-verbal aspects of the Palliative Care Team communication with children and families. In section three I consider the professional production of ‘companionship’. In this thesis I will demonstrate the significance of this concept according to the Palliative Care Team members and how care and communication are the base for the ‘production of companionship.’
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Lake, Elizabeth Mary. "Medicine and publishing in early nineteenth century Ireland : Production and consumption 1801-1858." Thesis, University of Ulster, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.532174.
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Irwin, Christa Kalberer. "The use of systematic reviews for decision making in animal production medicine and policy." [Ames, Iowa : Iowa State University], 2010. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:1476307.
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Ab, Razak Nur Izah. "MicroRNA modulation of aldosterone production in the adrenal gland." Thesis, University of Glasgow, 2016. http://theses.gla.ac.uk/7719/.
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Hypertension is the major risk factor for coronary disease worldwide. Primary hypertension is idiopathic in origin but is thought to arise from multiple risk factors including genetic, lifestyle and environmental influences. Secondary hypertension has a more definite aetiology; its major single cause is primary aldosteronism (PA), the greatest proportion of which is caused by aldosteroneproducing adenoma (APA), where aldosterone is synthesized at high levels by an adenoma of the adrenal gland. There is strong evidence to show that high aldosterone levels cause adverse effects on cardiovascular, cerebrovascular, renal and other systems. Extensive studies have been conducted to analyse the role that regulation of CYP11B2, the gene encoding the aldosterone synthase enzyme plays in determining aldosterone production and the development of hypertension. One significant regulatory factor that has only recently emerged is microRNA (miRNA). miRNAs are small non-coding RNAs, synthesized by a series of enzymatic processes, that negatively regulate gene expression at the posttranscriptional level. Detection and manipulation of miRNA is now known to be a viable method in the treatment, prevention and prognosis of certain diseases. The aim of the present study was to identify miRNAs likely to have a role in the regulation of corticosteroid biosynthesis. To achieve this, the miRNA profile of APA and normal human adrenal tissue was compared, as was the H295R adrenocortical cell line model of adrenocortical function, under both basal conditions and following stimulation of aldosterone production. Key differentially-expressed miRNAs were then identified and bioinformatic tools used to identify likely mRNA targets and pathways for these miRNAs, several of which were investigated and validated using in vitro methods. The background to this study is set out in Chapter 1 of this thesis, followed by a description of the major technical methods employed in Chapter 2. Chapter 3 presents the first of the study results, analysing differences in miRNA profile between APA and normal human adrenal tissue. Microarray was implemented to detect the expression of miRNAs in these two tissue types and several miRNAs were found to vary significantly and consistently between them. Furthermore, members of several miRNA clusters exhibited similar changes in expression pattern between the two tissues e.g. members of cluster miR-29b-1 (miR-29a-3p and miR-29b-3p) and of cluster miR-29b-2 (miR-29b-3p and miR-29c- 3p) are downregulated in APA, while members of cluster let-7a-1 (let-7a-5p and let-7d-5p), cluster let-7a-3 (let-7a-5p and let-7b-5p) and cluster miR-134 (miR- 134 and miR-382) are upregulated. Further bioinformatic analysis explored the possible biological function of these miRNAs using Ingenuity® Systems Pathway Analysis software. This led to the identification of validated mRNAs already known to be targeted by these miRNAs, as well as the prediction of other mRNAs that are likely targets and which are involved in processes relevant to APA pathology including cholesterol synthesis (HMGCR) and corticosteroidogenesis (CYP11B2). It was therefore hypothesised that increases in miR-125a-5p or miR- 335-5p would reduce HMGCR and CYP11B2 expression. Chapter 4 describes the characterisation of H295R cells of different strains and sources (H295R Strain 1, 2, 3 and HAC 15). Expression of CYP11B2 was assessed following application of 3 different stimulants: Angio II, dbcAMP and KCl. The most responsive strain to stimulation was Strain 1 at lower passage numbers. Furthermore, H295R proliferation increased following Angio II stimulation. In Chapter 5, the hypothesis that increases in miR-125a-5p or miR-335-5p reduces HMGCR and CYP11B2 expression was tested using realtime quantitative RT-PCR and transfection of miRNA mimics and inhibitors into the H295R cell line model of adrenocortical function. In this way, miR-125a-5p and miR-335-5p were shown to downregulate CYP11B2 and HMGCR expression, thereby validating certain of the bioinformatic predictions generated in Chapter 3. The study of miRNA profile in the H295R cell lines was conducted in Chapter 6, analysing how it changes under conditions that increase aldosterone secretion, including stimulation Angiotensin II, potassium chloride or dibutyryl cAMP (as a substitute for adrenocorticotropic hormone). miRNA profiling identified 7 miRNAs that are consistently downregulated by all three stimuli relative to basal cells: miR-106a-5p, miR-154-3p, miR-17-5p, miR-196b-5p, miR-19a-3p, miR-20b- 5p and miR-766-3p. These miRNAs include those derived from cluster miR-106a- 5p/miR-20b-5p and cluster miR-17-5p/miR-19a-3p, each producing a single polycistronic transcript. IPA bioinformatic analysis was again applied to identify experimentally validated and predicted mRNA targets of these miRNAs and the key biological pathways likely to be affected. This predicted several interactions between miRNAs derived from cluster miR-17-5p/miR-19a-3p and important mRNAs involved in cholesterol biosynthesis: LDLR and ABCA1. These predictions were investigated by in vitro experiment. miR-17-5p/miR-106a-p and miR-20b-5p were found to be consistently downregulated by stimulation of aldosterone biosynthesis. Moreover, miR-766-3p was upregulation throughout. Furthermore, I was able to validate the downregulation of LDLR by miR-17 transfection, as predicted by IPA. In summary, this study identified key miRNAs that are differentially-expressed in vivo in cases of APA or in vitro following stimulation of aldosterone biosynthesis. The many possible biological actions these miRNAs could have were filtered by bioinformatic analysis and selected interactions validated in vitro. While direct actions of these miRNAs on steroidogenic enzymes were identified, cholesterol handling also emerged as an important target and may represent a useful point of intervention in future therapies designed to modulate aldosterone biosynthesis and reduce its harmful effects.
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Edkins, Adrienne Lesley. "Integrin-ligand interactions and cytokine production by monocytic cells." Thesis, University of Glasgow, 2008. http://theses.gla.ac.uk/286/.
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CD23 is a Type II glycoprotein that exists in both membrane-bound (mbCD23) and soluble (sCD23) forms and functions as the low affinity receptor for IgE. CD23 interacts with a range of proteins to fulfil its function in vivo. Through interactions with its ligands IgE and CD21, CD23 regulates the levels of IgE in serum. Soluble CD23 also interacts with members of the integrin family of membrane receptors. Integrins are heterodimeric transmembrane receptors that participate in bidirectional signalling across membranes and have a critical role in cellular adhesion reactions. CD23 interacts with four integrins, αVβ3 and αVβ5 from the αV integrin family, and αMβ2 and αXβ2, from the β2 family of integrins. Using peptide array technology, we identified set of overlapping peptides derived from the soluble CD23 sequence that interact with integrins expressed on the surface of monocytic cells and with purified αVβ3 and αVβ5 integrins in in vitro Biacore assays. These peptides all contained a common basic tripeptide motif, termed the Arg-Lys-Cys (RKC) motif. Integrins traditionally recognise and bind the Arg-Gly-Asp (RGD) tripeptide in their ligands in a cation-dependent manner. However, the in vitro interaction between RKC-containing peptides and purified integrins was determined to be cation-independent, salt-sensitive and independent of RGD binding. The interaction was blocked by full length CD23. Substitution of the residues in the RKC motif reduced or abolished binding of the peptides to integrins expressed on cells and in vitro, as measured by Biacore analysis, and abolished the competition with CD23. Taken together, these data suggest that the RKC motif is the site in CD23 that is recognised and bound by αVβ3 and αVβ5 integrins. The RKC motif can be considered a novel recognition motif for integrins, as it is cation-independent, and its binding is not blocked by the presence of RGD-containing integrin ligands. Therefore it is likely that the RKC motif interacts with integrins at a site other than that used for RGD-binding, similar to the interactions that have been described for the binding of the HIV Tat protein. The interaction between sCD23 and its integrin receptors is important in the regulation of cytokine production by monocytic cells. Most monocytic cells will express a combination of the different CD23-binding integrins simultaneously and, therefore, the cytokine output of that cell will be the net result of the interaction of CD23 with a combination of integrins. We used monoclonal antibodies to investigate the role of individual integrins in cytokine production. Antibodies were selected to allow comparision of the cytokine response between, a) integrin families, b) integrin subunits, and c) integrin epitopes. The cytokine profile induced by integrin ligation did not differ between the αV and β2 integrin families, although the concentration of cytokines produced varied depending on the heterodimer targeted. However, within a particular family, cytokine production induced by integrin ligation was specific and relied on the recognition of a precise epitope on the integrin. Cytokine production by CD23-binding integrins appears to require the ligation of the α subunit of the integrin heterodimer. We identified an antibody directed against the αVβ3 integrin that induced high levels of cytokine production. Cytokine production following ligation of the integrin with this antibody was dependent on activation of the ERK/MAPK pathway in cells. This production of cytokines and phosphorylation of ERK was enhanced by the addition of macrophage colony stimulating factor (M-CSF) and partially inhibited by an anti-TLR-2 antibody. Chronic stimulation (<3 days) of THP-1 cells with the anti-αVβ3 antibody in the presence of M-CSF led to morphological changes in the cell line associated with the development of a more macrophage-like phenotype and the continued production of cytokines. Analysis of the changes in cell surface marker expression and cytokine profiles suggested that the THP-1 cells had undergone an M2b programme of macrophage activation in response to αVβ3 ligation. Data presented herein reinforce the importance of the role of integrins in the control of adhesion-independent signalling pathways in suspension cells.
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Till, Stephen James. "Regulation of T-cell interleukin-5 production and proliferation in allergic disease." Thesis, Imperial College London, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.267241.
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Smith, Sharon Lesley. "Production of markers of neurological damage induced by cerebral ischaemia or neurotoxins." Thesis, University of Nottingham, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.359770.
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Allaker, R. P. "The production of cytotoxic and inflammatory compounds by skin and oral microorganisms." Thesis, University of the West of England, Bristol, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.355849.
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Zweit, Jamal H. "The production of medium half-life radionuclides for positron emission tomography." Thesis, University of Manchester, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.257443.
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Malu, Muia Ndavi. "Production and role of #gamma#-interferon during Theileria parva infections." Thesis, University of Cambridge, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.259628.
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Lentmaier, Claudia. "Characterization of capsaicinoid production in recombinant Saccharomyces cerevisiae." Thesis, Malmö universitet, Fakulteten för hälsa och samhälle (HS), 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:mau:diva-27076.
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Kapsaicinoider är ämnen som finns i chilifrukterna och har på senaste tiden fått intresse som läkemedel på grund av sina analgetiska, anti-inflammatoriska och anti-cancer egenskaper. Ett nytt tillvägagångssätt att producera kapsaicinoider kan vara syntesen i rekombinant Saccharomyces cerevisiae med hjälp av metabolisk engineering och rekombinant DNA-tekniker. Gener från Capsicum chinensis, som kodar för enzymerna capsaicinoid-syntas (CS) och acyl-CoA-syntas (ACS), integrerades i S. cerevisiae i tidigare projekt. Den kända laboratoriesträngen CEN.PK modifierades med plasmidtransformation och för vildtyp-stammen ERF 5273 användes den nya CRISPR/Cas9-tekniken. Syftet med detta projekt är att ytterligare karakterisera och jämföra dessa tidigare konstruerade stammar angående deras förmåga att producera nonivamid eller andra jästspecifika kapsaicinoider. Vidare undersöks huruvida kapsaicinoider utsöndras i odlings-medium eller om de ackumuleras intracellulärt. Stammarna odlades i en bioreaktor i lite laboratorieskala. Som odlingsmedium används ett definierat medium med eller utan tillsatser. Odlings-medium kompletterades med vanillyl-amin och nonanoic acid som precursor. För att identifiera de kapsaicinoid-producerande stammarna extraherades supernatanten och cellpelleten och analyserades kromatografisk med HPLC. Resultaten från denna studie visade att jäststammarna, som innehöll båda generna (ACS + CS), sannolikt producerade nonivamid om de odlades i kompletterat medium. Vidare observerades bildning av nonivamid som ackumulerades i själva cellen. Möjligtvis producerades också jästspecifika kapsaicinoider, men topphöjden är nästan inte mätbar. Därför måste dessa resultat bekräftas ytterligare. Framtida arbeten behövs för att säkerställa och förbättra produktionen av kapsaicinoider.Keywords: acyl-CoA syntas, kapsaicinoider, kapsaicinoid syntas, metabolisk engineering, Saccharomyces cerevisiae, nonivamideCapsaicinoids are compounds found in chili plants and have recently gained interest as pharmaceuticals due to their analgesic, anti-inflammatory and anti-cancer properties. A novel approach producing capsaicinoids could be synthesis in recombinant Saccharomyces cerevisiae with help of metabolic engineering. Genes from Capsicum chinensis, encoding the enzymes capsaicinoid synthase (CS) and acyl-CoA synthase (ACS), were previously inserted into S. cerevisiae. The known laboratory stain CEN.PK was modified with plasmid transformation and the novel CRISPR/Cas9 technology was used for the wild type strain ERF 5273. The aim of this project is to further characterize and compare these previously constructed strains concerning their ability to produce nonivamide or yeast specific capsaicinoids. Furthermore, it is examined whether capsaicinoids are excreted into the broth or accumulated intracellularly. Four different strains were cultivated in bench-scale bioreactors using medium supplemented with or without different precursors (vanillylamine and nonanoic acid). Culture broth supernatants and cell pellets were extracted and analyzed by HPLC in order to identify the capsaicinoid-producing strains. The results from this study revealed that the yeast strains harbouring both genes (ACS+CS) produced most likely nonivamide if they were cultivated in media supplemented with both precursors. Nonivamide formation was equally observed in broth supernatant and cell pellet. Additionally it was shown that yeast specific capsaicinoid production occured, althoug the peak height was close to the limit of detection and these results have to be confirmed further. Future work needs to be done in order to ensure and improve capsaicinoid production.Keywords: acyl-CoA synthase, capsaicinoids, capsaicinoid synthase, metabolic engineering, Saccharomyces cerevisiae, nonivamide.
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Rovedatti, Laura. "Differential regulation of interleukin-17 and interferon-y production in inflammatory bowel disease." Thesis, Queen Mary, University of London, 2010. http://qmro.qmul.ac.uk/xmlui/handle/123456789/1272.
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Background and Aims. Interleukin (IL)-17 is now known to be involved in a number of chronic inflammatory disorders. However, the mechanisms regulating its production in inflammatory bowel disease (IBD) are still unclear. Methods. Endoscopic biopsies or surgical specimens were taken from inflamed and uninflamed colonic mucosa of 72 IBD patients (38 with Crohn’s disease and 34 with ulcerative colitis), and normal colon of 38 control subjects. IL-17 and interferon (IFN)- were detected by ELISA in the supernatants of biopsies cultured ex vivo, and anti-CD3/CD28-stimulated lamina propria mononuclear cells (LPMCs) incubated with IL-12, IL-23, IL-1β plus IL-6, transforming growth factor (TGF)-β1, or anti-IL-21 neutralising antibody. Intracellular flow cytometry was performed to analyse mucosal Th17 and Th1/Th17 cells. Results. IL-17 production by organ culture biopsies was higher in IBD inflamed mucosa than IBD uninflamed mucosa and controls, and was equivalent in amount to IFN-. Anti-CD3/CD28-stimulated IBD LPMCs produced higher IL-17 amounts compared to controls. The percentages of Th17 and Th1/Th17 cells were increased in IBD patients than controls. IL-23 and IL-1 plus IL-6 had no effect on IBD LPMC production of IL-17, however IL-12 markedly increased IFN- production and decreased IL-17 production. TGF-β1 dose-dependently decreased IFN-, but had no significant inhibitory effect on IL-17 production. Blocking IL-21 significantly down-regulated IL-17 production. Conclusions. Our findings support a role for IL-12, TGF- and IL-21 in modulating IL-17/IFN- production in IBD. The abundant IL-17 in inflamed IBD mucosa may help explain the relative lack of efficacy of anti-IFN- antibodies in clinical trials of Crohn’s disease.
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Rohloff, Jens. "Cultivation of Herbs and Medicinal Plants in Norway - Essential Oil Production and Quality Control." Doctoral thesis, Norwegian University of Science and Technology, Department of Biology, 2003. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-415.
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Essential oils (EO) are plant secondary metabolites that are known for their fragrance and food flavour properties. They consist of a complex mixture of mono- and sesquiterpenes, phenyl propanoids and oxygenated compounds. EOs can be present in different plant organs and materials, and their storage is related to specialised secretory structures. The yield of EOs from plant raw materials by distillation or pressing may on average vary from 0.1 – 1%, thus restricting the major EO production to the plant group of aromatic plants. Due to their function as signalling compounds between different types of organisms and diverse biological systems, their general antimicrobial and antioxidative effects and medicinal activity, EOs offer a promising potential for future applications within the fields of agriculture, medicine, pharmaceutical industry and biotechnology.
Changed consumer demands and raised interest in natural product compounds, especially essential oils, have formed the basis for initiating the research project “Norwegian Herb Production (Norsk Urteproduksjon NUP)” to encourage the cultivation, processing, marketing and distribution of aromatic and medicinal plants. The production, composition and quality characteristics of EOs (yield and terpene composition) from chamomile, lemon balm, oregano, peppermint, sachalinmint, thyme and yarrow have been investigated in the project period between 1994-1998.
Much focus has been put on the application of solid-phase microextraction (SPME) coupled with gas chromatography-mass spectrometry (GC-MS) for the analysis of EO volatiles from various aromatic and medicinal plants. SPME is a fast, solvent-free and non- destructive sample preparation technique where the analytes are extracted from fluid or solid matrices by headspace (HS) or direct immersion sampling (DI). Apart from EO isolation by common distillation, the applicability and sensitivity of the SPME fibre has made it feasible to carry out qualitative and semi-quantitative HS analyses of aromatic plants with regard to changes of EO metabolism during ontogenesis and plant development.
Based on NUP-results from field trials in the period between 1995-1996, the mint species peppermint (Mentha × piperita L.) and sachalinmint (Mentha sachalinensis (Briq.) Kudô) have been studied in detail (Papers B, D and E). Comparative analyses by applying distillation sampling and SPME have been carried out in order to study the advantages and disadvantages of both techniques (Papers B and E). It could be shown, that SPME offers a fast and reliable method for detecting quality-impact compounds from the p-menthane group (menthol, menthone, neomenthol, isomenthone and menthyl acetate). A distinct increase in the menthol/menthone ratio in the basipetal direction could be detected for peppermint and sachalinmint by applying SPME, thus revealing within-plant quality differences according to pharmacopeial requirements. Taking the increase of EO production from the vegetative to the generative growth stage into account, the harvest of mint plants in bloom will result in better EO yield and quality with regard to higher amounts of menthol.
When applying HS-SPME on complex EO volatile matrices such as known for yarrow (Achillea millefolium L.; Paper C), one might deal with fibre-partitioning effects of the different mono- and sesquiterpenes due to their physical and chemical properties. Despite these disadvantages, HS-SPME appears to be a sensitive extraction method for the screening of EO volatiles from complex sample matrices. Comparative analyses of volatiles from rose root rhizomes (Rhodiola rosea L.) have been carried out in order to characterize the rose-like odour compounds (Paper F). A total of 75 and 59 compounds have been identified by distillation sampling and HS-SPME, respectively, thus underscoring the excellent extraction properties and applicability of the SPME fibre.
Paper A gives a brief overview of EO biosynthesis and chemical structures, plant sources and methods of EO production. Before leading over to the main topic of HS-SPME applications by referring to numerous examples from the research work at The Plant Biocenter in the past 5 years, an introduction of solid-phase microextraction with regard to devices, procedures and extraction parameters is given.
The advantages and disadvantages of distillation vs. SPME are outlined on the background of comparative analyses of peppermint, chamomile, basil and dill. Furthermore, the utilization of HS-SPME for quantitative studies with regard to extraction time and analyte concentration is being highlighted. Examples for the screening of chemotypes (hops −Humulus lupulus L.) and cultivars (dill – Anethum graveolens L.) and ontogenetic studies are given (Mentha species; arnica −Arnica montana L.). Finally, the applicability of HS-SPME for the quality assessment of processed herbs (sweet basil −Ocimum basilicum L.) and phytomedicinal preparations (red coneflower – Echinacea purpurea L.) is being discussed.
The advantages of HS-SPME over classical distillation and headspace applications are impressive due to drastically reduced analysis time and will introduce new frontiers in plant volatile research with regard to secondary metabolism, plant-insect interactions and in vivo studies. The user-friendliness of operating SPME will initiate the development of future applications and equipment for the monitoring of volatiles for plant biological and environmental studies, extraction automation, on-site sampling and on-fibre storage of analytes.
Paper VI reprinted with kind permission of Elsevier, Sciencedirect, www.sciencedirect.com
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MORAES, VANESSA. "Desenvolvimento de um metodo de preparacao de um tracador de estanho, o sup[117m]Sn, a partir da irradiacao de estanho natural com feixe de protons do Ciclotron do IPEN." reponame:Repositório Institucional do IPEN, 2000. http://repositorio.ipen.br:8080/xmlui/handle/123456789/9285.
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Made available in DSpace on 2014-10-09T12:25:41Z (GMT). No. of bitstreams: 0Made available in DSpace on 2014-10-09T14:03:41Z (GMT). No. of bitstreams: 1 06873.pdf: 3893215 bytes, checksum: 6d198b442dc331f7ee99c5eb2cd23c10 (MD5)
Dissertacao (Mestrado)
IPEN/D
Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP
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Bishop, Simon. "HRM in public private partnerships : working in a health production system." Thesis, University of Nottingham, 2011. http://eprints.nottingham.ac.uk/12159/.
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This study explores the changing nature of employment and employment management within multi-organisational public services ‘partnerships’. In line with international trends, a major feature of the 1997-2010 New Labour government’s public policy was encouraging partnerships between organisations of all sectors to run public services. Within healthcare, central government has increasingly been seen as taking on a role of market regulator, with organisations from all sectors allowed to plan as well as provide public services (Illife and Munro, 2000). As part of this picture, bringing private companies into partnership arrangements with the National Health Service has been seen as a catalyst for workforce re-configuration and employment change through furthering the reach of private sector type Human Resource Management. However, research has illustrated how inter-organisational contracts can also restrict an organisations choice of employment practice, disrupt the direct relationship between managers and employees, and undermine any aspirations for fair or consistent employment (Marchington et al, 2005). In more recent healthcare partnerships, employment is further complicated as partnerships involve powerful professional groups with their own protected employment systems and established norms of practice. This study seeks to investigate the prospects for HRM within such a professionalised partnership context through comparative case study of two Independent Sector Treatment Centres (ISTCs) operating under differing employment regulations and contractual agreements. In both cases, private sector management sought to impose a more ‘rationalised’ and standardised approach to work with a greater focus on outputs and productivity, placing ISTCs at the forefront of the Fordist ‘scientific-bureaucratic’ (Harrison, 2002) approach to medicine. However, the study identifies a number of limits to the degree to which the management of the private health care companies could shape HRM practices in line with these aims. The thesis also examines how being separate from, or integrated with, existing National Health Service organisations can lead to different types of contingencies affecting work and employment, and multiple varieties of inconsistency across the workforce. The findings of the study are explored in terms of the implications for public policy, health service management and HRM theory.
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McLoughlin, Eimear Maureen. "Time series analysis and modelling of diseases in production animal populations." Thesis, Queen's University Belfast, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.334509.
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Pourazar, Jamshid. "Activation of epithelial signal transduction pathways, cytokine production and airway inflammation following diesel exhaust exposure." Doctoral thesis, Umeå : Department of Public Health and Clinical Medicine, Umeå University, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-795.
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Julin, Madeleine. "Tar production – traditional medicine and potential threat to biodiversity in the Marrakesh region: An ethnobotanical study." Thesis, Uppsala universitet, Systematisk biologi, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-141824.
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Manenti, S. "RADIONUCLIDES FOR MEDICINE - EXCITATION FUNCTIONS FOR THE PRODUCTION OF TC-99M, ZR-89 AND PD-103." Doctoral thesis, Università degli Studi di Milano, 2017. http://hdl.handle.net/2434/476931.
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The production of radionuclides for medicine is one of the most important directions of nuclear chemistry and nuclear industry. Radionuclides are used both for medical diagnostics of various diseases as well as for internal radiotherapy: the consumption of pharmaceuticals based on radioactive isotopes is growing fast.
The main amount of commercial medical radionuclides is produced on nuclear reactors but more and more radiopharmaceuticals are produced on the base of accelerator produced isotopes. Even if the accelerator production is more expensive, it can provide a wider range of radionuclides and often provide higher specific activity.
This work is focused on the production optimization of three main radionuclides Tc-99m, Zr-89 and Pd-103 irradiating, correspondingly, targets of enriched molybdenum-100, natural yttrium-89 and natural rhodium-103 with proton or deuteron beams accelerated by cyclotrons. Formation of several by-products synthesized in the same targets is also investigated because it is important to understand the presence of all the possible impurities to be removed with the radiochemical procedures.
All these radionuclides are important and used in nuclear medicine.
Tc-99m is considered the “workhorse” of radiopharmaceutical imaging and it is usually obtained from another radioactive parent isotope Mo-99 produced mostly in the world on nuclear reactors. However, in the last years, the direct production of Tc-99m from the Mo-100-enriched targets in low-energy proton accelerators – nuclear reaction (p, 2n) – is considered as possible substitution of reactor production and has good prospects for local needs.
Zr-89 is a radionuclide extremely prospective for labelling monoclonal antibodies, bio-distribution studies, and immuno-positron emission tomography (PET) imaging.
Pd-103 is used in brachytherapy and, with the rapid development of nanoscience and nanotechnology, it becomes appealing to make injectable nano-scale brachytherapy seeds.
The production of Zr-89 and Pd-103 by protons was well studied and considered. In contrast, there are few experimental data on the excitation functions of the deuteron-induced nuclear reactions or these are rather scattered: the (d,2n) reaction appears to be very attractive and it deserves particular interest of study.
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Restrick, Louise Jane. "Cytokine and leukotriene production in asthma : bronchoalveolar lavage studies in asthmatic and normal subjects." Thesis, Queen Mary, University of London, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.266178.
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Inglis, G. E. "Human blood group specific monoclonal antibody production using immunogens derived from non-human sources." Thesis, Open University, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.383844.
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Bostanci, Nagihan. "Interleukin-1[Alpha] production in periodontal disease : the interaction of bacteria and gene polymorphisms." Thesis, Queen Mary, University of London, 2007. http://qmro.qmul.ac.uk/xmlui/handle/123456789/1419.
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There is good evidence that interleukin-I alpha (IL-Ia) plays a key role in both the host response to bacteria and the tissue destruction associated with periodontal disease. This thesis investigated the interaction of bacterial, genetic and pharmacological factors in the regulation of IL-la in periodontal disease. To investigate the stimulation of IL-la by periodontal pathogens, human monocytes were challenged with a wide range of periodontal species. Most of the species tested stimulated high levels of IL-la. Induction by P. gingivalis was notably weak. Co-stimulation with P. gingivalis antagonised the ability of other bacterial species to induce IL-la, and this antagonism was due to the specific nature of its LPS. The association of periodontal. disease with host genetic variation was investigated by screening the IL-lA promoter region by direct sequencing in patients with aggressive periodontitis. Three single-nucleotide polymorphisms (SNPs) were identified including rs3783521 C>T, rs1800794 C>T, rs1800587 C>T. However, the prevalence of polymorphic alleles between patients and healthy subjects was similar. To test if any of these polymorphisms effect transcription of IL-IA, the polymorphisms of interest were introduced into an IL-lu luciferase reporter construct by site-directed mutagenesis. Only one of these polymorphisms, rs1800587 (-899), resulted in a significant change in transcription using transient transfection assays. The T allele of this SNP reduced both the basal activity and the response to LPS or periodontopathogens. Therefore, the rs1800587 SNP might play a role in the regulation of IL-lA gene transcription induced by bacteria. The central role played by IL-1 a in the pathogenesis of periodontal disease suggests that immunomodulation may offer a therapeutic option. Sub-antimicrobial concentrations of doxycycline inhibited IL-Ict production in response to bacterial stimulation by human monocytes. This effect appears to be at translational level rather than transcription. It does not appear to involve the regulation of NF-icB activity, or the suppression of IL-Ict transcription, or doxycycline chelation properties. In conclusion, IL-la is a pivotal cytokine involved in periodontal disease, and its regulation is a complex event governed by bacterial factors, host genetics and pharmacological agents.
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Connolly, Kim. "Artificial limb cosmesis design : a study of materials and production methods for improved performance." Thesis, University of Surrey, 1990. http://epubs.surrey.ac.uk/843828/.
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A strain analysis of the foams used as cosmeses for artificial limbs was conducted. It was found that on flexion of an artificial limb strain occurred in the knee region. The mechanical properties of cosmeses materials suggested that the foams would not fail at the strain levels measured when undamaged. However, when the foam became cracked the properties of the foams were reduced to a level that would make failure likely to occur when the cracks reached critical lengths. The failure mechanism of the foam coverings was established via the use of a test rig, designed and built to simulate the interaction between the artificial limb patella piece and the foam. Foam samples were tested both with and without protective elastic netting. The primary cause of failure was found to be wear induced cracking. It was recommended that the design of the patella piece should be changed so as to be less damaging, and that netting should be used for all foams. Silicone foam materials were formulated and investigated for their suitability as a cosmesis foam. Silicone foam samples were tested on the fatigue test rig. Skinned silicone foams with netting had lifetimes three times that of any cosmesis foam tested in a condition currently used in production procedure, and 35% longer than any foam tested in any condition. It was found from leg measurement studies that there was a general leg shape for males and females. Details of leg shapes were transferred to a C.A.D. system. A match from the C.A.D. system for a single amputee's limb can be found. The accuracy of matching is at worst 5%. The current accuracy of matching is generally 15%. The information from the C.A.D. system can be used either to produce moulds for a cosmesis moulding system, or be used in conjunction with a C.N.C. lathe for the direct cutting of cosmeses.
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Ito, Yukitaka. "Turbulence Activates Platelet Biogenesis to Enable Clinical Scale Ex Vivo Production." Kyoto University, 2020. http://hdl.handle.net/2433/252983.
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Ferraro, Alastair James. "Probing the sensitivity of autoantibody production to B cell depletion by Rituximab." Thesis, University of Birmingham, 2010. http://etheses.bham.ac.uk//id/eprint/691/.
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Rituximab, a monoclonal antibody directed against the human CD20 antigen, causes profound depletion of all B cells. When used in patients with autoimmune disease, IgG autoantibody titres often fall whilst serum IgG anti-tetanus toxoid antibody titres are unaffected. Antibodies of both these antibody specificities have features associated with production by long-lived CD20- plasma cells that should be resistant to Rituximab. Reasons for the differential loss of these apparently similar types of antibody were investigated. Initial experiments established multiplexed bead assays to measure, in parallel, serum titres of multiple antibody specificities. Paired acute and convalescent sera, from 11 patients treated with Rituximab for Wegener‟s granulomatosis, were then studied. During 5 months after treatment, and following clinical remission, IgG anti-Proteinase 3 autoantibody titres fell gradually. All other measured antibody titres remained little changed. These findings favour the hypothesis that autoantibody producing plasma cells are sustained by disease related inflammation. Subsequent experimental studies support a wider hypothesis -that inflamed sites can support increased plasma cell numbers. In the prolific humoral response of QM mice to immunisation with NP-Ficoll, concurrent infection with attenuated Salmonella enterica serovar Typhimurium increases splenic capacity to support plasma cells. The enhanced support may reflect locally increased IL-6 production.