La vectorisation des médicaments est une approche très prometteuse tant sur le plan médical qu’économique pour la livraison des substances actives ayant une faible biodisponibilité. Dans ce contexte, les polymères en étoile et les dendrimères, macromolécules symétriques et branchées, semblent être les solutions de vectorisation les plus attrayantes. En effet, ces structures peuvent combiner efficacement une stabilité élevée dans les milieux biologiques à une capacité d’encapsulation des principes actifs. Grâce à leur architecture bien définie, ils permettent d’atteindre un très haut niveau de reproductibilité de résultats, tout en évitant le problème de polydispersité. Bien que des nombreuses structures dendritiques aient été proposées ces dernières années, il est cependant à noter que la conception de nouveaux nanovecteurs dendritiques efficaces est toujours d’actualité. Ceci s’explique par des nombreuses raisons telles que celles liées à la biocompatibilité, l’efficacité d’encapsulation des agents thérapeutiques, ainsi que par des raisons économiques. Dans ce projet, de nouvelles macromolécules branchées biocompatibles ont été conçues, synthétisées et évaluées. Pour augmenter leur efficacité en tant qu’agents d’encapsulations des principes actifs hydrophobes, les structures de ces macromolécules incluent un coeur central hydrophobe à base de porphyrine, décanediol ou trioléine modifié et, également, une couche externe hydrophile à base d’acide succinique et de polyéthylène glycol. Le choix des éléments structuraux de futures dendrimères a été basé sur les données de biocompatibilité, les résultats de nos travaux de synthèse préliminaires, ainsi que les résultats de simulation in silico réalisée par une méthode de mécanique moléculaire. Ces travaux ont permis de choisir des composés les plus prometteurs pour former efficacement et d’une manière bien contrôlable des macromolécules polyesters. Ils ont aussi permis d’évaluer au préalable la capacité de futurs dendrimères de capter une molécule médicamenteuse (itraconazole). Durant cette étape, plusieurs nouveaux composés intermédiaires ont été obtenus. L’optimisation des conditions menant à des rendements réactionnels élevés a été réalisée. En se basant sur les travaux préliminaires, l’assemblage de nouveaux dendrimères de première et de deuxième génération a été effectué, en utilisant les approches de synthèse divergente et convergente. La structure de nouveaux composés a été prouvée par les techniques RMN du proton et du carbone 13C, spectroscopie FTIR, UV-Vis, analyse élémentaire, spectrométrie de masse et GPC. La biocompatibilité de produits a été évaluée par les tests de cytotoxicité avec le MTT sur les macrophages murins RAW-262.7. La capacité d’encapsuler les principes actifs hydrophobes a été étudiée par les tests avec l’itraconazole, un antifongique puissant mais peu biodisponible. La taille de nanoparticules formées dans les solutions aqueuses a été mesurée par la technique DLS. Ces mesures ont montré que toutes les structures dendritiques ont tendance à former des micelles, ce qui exclue leurs applications en tant que nanocapsules unimoléculaires. L’activité antifongique des formulations d’itraconazole encapsulé avec les dendrimères a été étudiée sur une espèce d’un champignon pathogène Candida albicans. Ces tests ont permis de conclure que pour assurer l’efficacité du traitement, un meilleur contrôle sur le relargage du principe actif était nécessaire. / The drug molecule vectorization is a very promising approach in terms of both medical and economical factors for the delivery of active substances with low bioavailability. In this context, the star polymers and dendrimers, symmetrical and branched macromolecules, seem to be more attractive solutions. Indeed, these structures can effectively combine a high stability in biological media and the ability to encapsulate active ingredients. Thanks to the well-defined architecture, they can achieve a high level of reproducibility of results, while avoiding the problem of polydispersity. In recent years, many dendritic structures have been proposed; however, the design of new effective dendritic nanocarriers is still relevant. This is due to many reasons such as related to biocompatibility, encapsulation efficiency of therapeutic agents, as well as economic reasons. In this project, new branched biocompatible macromolecules were designed, synthesized and evaluated. To increase their effectiveness as encapsulation agents for hydrophobic active principles, the structures of the proposed macromolecules include a hydrophobic central core on the basis of porphyrin, decanediol or modified triolein, and also a hydrophilic outer layer based on succinic acid and polyethylene glycol. The choice of structural elements of future dendrimers was based on the data on their biocompatibility and the results of our preliminary synthesis works, as well as the in silico simulations performed by using the method of molecular mechanics. The preliminary studies allowed for selecting the most promising compounds to effectively form polyesters macromolecules in well controlled manner, as well as to assess in advance the ability of future dendrimers to capture a drug molecule (itraconazole). During this phase, several new intermediates were obtained. The optimization of reaction conditions leading to high yields was performed. Based on the preliminary work, the assembly of new dendrimers of first and second generations was performed, by using the divergent and convergent synthesis approaches. The structures of new compounds were characterized by proton and 13C carbon NMR, FTIR, UV-Vis, elemental analysis, mass spectrometry, and GPC techniques. The biocompatibility of products was evaluated by cytotoxicity tests with MTT on murine RAW 262.7 macrophages. The ability to encapsulate hydrophobic active principles was studied by testing with itraconazole, an antifungal agent with low bioavalability. The size of nanoparticles formed in aqueous solutions was measured by the DLS technique. These measurements showed that all dendritic structures tend to form micelles, which excludes their application as unimolecular nanocapsules. The antifungal activity of itraconazole formulations with dendrimers was studied in a kind of a pathogenic fungus Candida albicans. These tests lead to the conclusion that to ensure the effectiveness of treatment, more control over the release of the active ingredient has been needed.

One of the aims included in the United Nations Millennium Development Goals is to decrease the number of the world’s population without access to sanitation and water that is safe, by half by the year 2015. The use of water that is not safe for consumption leads to water–related diseases. For the purpose of this study gastro–intestinal disease was redefined as diseases of the gastro–intestinal tract caused by pathogens that spread via contaminated drinking water, poor sanitation and inadequate hygiene. Information obtained regarding the use of gastro–intestinal disease medication, may provide information about the prevalence of gastro–intestinal disease in South Africa. The general objective of this study was to determine the prescribing patterns of gastro–intestinal medication in different geographical areas in the private health care sector of South Africa. A retrospective drug utilisation review was conducted on data obtained from a medicine claims database of a pharmacy benefit management company for 2007 and 2008. A pharmacoepidemiological approach was followed in order to determine the prevalence of gastro–intestinal disease as well as the use of gastro–intestinal medication in South Africa as well as the different provinces of South Africa. The impact of water quality and sanitation on the prevalence of gastro–intestinal disease was also investigated. Gastro–intestinal medication (used in the treatment of gastro–intestinal disease) included the following pharmacological groups according to the MIMS®–classification: antivertigo and anti–emetic agents (group 1.8), antispasmodics (group 12.3), antidiarrhoeals (group 12.7), minerals and electrolytes (group 20.4, selected according to specified NAPPI–codes) and antimicrobials (group 18). Antimicrobials had to be prescribed in combination with one of the specified gastro–intestinal medication groups in order to be classified as a gastro–intestinal medication. In 2007 and 2008 respectively, 428864 and 340921 gastro–intestinal medication items were prescribed. The most frequently prescribed gastro–intestinal medication pharmacological groups in 2007 and 2008 were beta–lactam antimicrobials (with proportion percentages of 22.77% and 20.85% in 2007 and 2008 respectively), antivertigo and anti–emetic agents, antispasmodics, antidiarrhoeals and quinolone antimicrobials. Minerals and electrolytes represented only a small proportion (2.99% and 2.56% in 2007 and 2008 respectively) of the prescribed gastro–intestinal medication in South Africa. In the Free State and Western Cape antivertigo and anti–emetic agents were the most frequently prescribed gastro–intestinal medication items, while in other provinces beta–lactam antimicrobials ranked the highest. In all provinces except the Western Cape and the Northern Cape, amoxicillin/clavulanic acid was the most frequently prescribed gastro–intestinal medication active ingredient. In the Western Cape loperamide was the most frequently prescribed active ingredient, while ciprofloxacin ranked highest as active ingredient in the Northern Cape in 2008. Based on the prescribing patterns of gastro–intestinal disease medications the treatment of gastro–intestinal disease in this section of the private health care sector of South Africa, does not fully comply with the Standard Treatment Guidelines with regard to the use of antimicrobials and electrolyte replacement therapy. / Thesis (M.Pharm. (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2011.

One of the aims included in the United Nations Millennium Development Goals is to decrease the number of the world’s population without access to sanitation and water that is safe, by half by the year 2015. The use of water that is not safe for consumption leads to water–related diseases. For the purpose of this study gastro–intestinal disease was redefined as diseases of the gastro–intestinal tract caused by pathogens that spread via contaminated drinking water, poor sanitation and inadequate hygiene. Information obtained regarding the use of gastro–intestinal disease medication, may provide information about the prevalence of gastro–intestinal disease in South Africa. The general objective of this study was to determine the prescribing patterns of gastro–intestinal medication in different geographical areas in the private health care sector of South Africa. A retrospective drug utilisation review was conducted on data obtained from a medicine claims database of a pharmacy benefit management company for 2007 and 2008. A pharmacoepidemiological approach was followed in order to determine the prevalence of gastro–intestinal disease as well as the use of gastro–intestinal medication in South Africa as well as the different provinces of South Africa. The impact of water quality and sanitation on the prevalence of gastro–intestinal disease was also investigated. Gastro–intestinal medication (used in the treatment of gastro–intestinal disease) included the following pharmacological groups according to the MIMS®–classification: antivertigo and anti–emetic agents (group 1.8), antispasmodics (group 12.3), antidiarrhoeals (group 12.7), minerals and electrolytes (group 20.4, selected according to specified NAPPI–codes) and antimicrobials (group 18). Antimicrobials had to be prescribed in combination with one of the specified gastro–intestinal medication groups in order to be classified as a gastro–intestinal medication. In 2007 and 2008 respectively, 428864 and 340921 gastro–intestinal medication items were prescribed. The most frequently prescribed gastro–intestinal medication pharmacological groups in 2007 and 2008 were beta–lactam antimicrobials (with proportion percentages of 22.77% and 20.85% in 2007 and 2008 respectively), antivertigo and anti–emetic agents, antispasmodics, antidiarrhoeals and quinolone antimicrobials. Minerals and electrolytes represented only a small proportion (2.99% and 2.56% in 2007 and 2008 respectively) of the prescribed gastro–intestinal medication in South Africa. In the Free State and Western Cape antivertigo and anti–emetic agents were the most frequently prescribed gastro–intestinal medication items, while in other provinces beta–lactam antimicrobials ranked the highest. In all provinces except the Western Cape and the Northern Cape, amoxicillin/clavulanic acid was the most frequently prescribed gastro–intestinal medication active ingredient. In the Western Cape loperamide was the most frequently prescribed active ingredient, while ciprofloxacin ranked highest as active ingredient in the Northern Cape in 2008. Based on the prescribing patterns of gastro–intestinal disease medications the treatment of gastro–intestinal disease in this section of the private health care sector of South Africa, does not fully comply with the Standard Treatment Guidelines with regard to the use of antimicrobials and electrolyte replacement therapy. / Thesis (M.Pharm. (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2011.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The soybean cultivars reaction to the causal agent of asian rust (Phakopsora pachyrhizi Syd. & P. Syd.) and mixing responsiveness of DeMethylation Inhibitor (DMI) and Quinone outsite Inhibitor (QoI) fungicides are important factors to be determined for the management of the pathogen. The activity of these fungicides sprayed on the leaves depends on the amount that it reaches the biochemical action site and the compound efficacy. Thus, the proportion of leaf deposit that it enters the leaf, the rate of entry and dissipation in the leaf tissue are determinant for the activity and diseases residual control after the occurrence of a wash. The chapter I objective was to evaluate the reaction of fifteen soybean cultivars to the causal agent of soybean rust and the responsiveness mixing Active Ingredients (AI) epoxiconazole (EPOX) + pyraclostrobin (PYR) and prothioconazole (PROT) + trifloxystrobin (TRIFL). The parameters evaluated were the latency period, residual control, progression and the Area Under the Disease Progress Curve (AUDPC). In the Chapter II, the EPOX and PYR persistence associated with mancozeb (Mz) was determined under greenhouse conditions in two commercial soybean cultivars. Artificial washes were used to determine the concentration of the remaining AI on the foliar tissues after the spraying. For this purpose, the leaves were washed with water at 0.17, 1, 2, 4, 48, 96, 192 h after the fungicide spraying and immediately collected. The EPOX and PYR concentrations were also determined on leaves at 12, 16 and 20 days after spraying. Through the high performance liquid chromatographic analysis and the experimental design, it was possible to measure the EPOX and PYR concentrations penetrated and it dissipated in whole-plant leaves, associated or not to mancozeb. The influence of the interaction between leaflets age and cultivars in the EPOX and PYR concentration on leaves after the spraying was also evaluated. Due to the scarcity of detailed studies on the performance of site-specific fungicides associated with multisite fungicides, in the Chapter III was investigated the asian rust severity and the residual control of the EPOX and PYR mixture associated mancozeb. In the chapter I, it was verified that the responsiveness of DMI and QoI mixtures to P. pachyrhizi is different among the cultivars. The greatest residual control of the pathogen in the different cultivars was through of the PROT + TRIFL spraying. In the chapter II, it was verified that mancozeb influences the persistence of DMI and QoI fungicides in soybean cultivars. The EPOX penetration rate in the cultivars was faster without the association of mancozeb to the fungicide (DMI + QoI). The association of mancozeb to the fungicide (DMI + QoI) reduced the penetration rate of PYR in DM 6563 RSF IPRO cultivar. The PYR concentration in leaves of the two cultivars at 48 h after spraying was similar by the association or not of the fungicide with mancozeb. The cultivars showed different AI penetration rates in leaves. It was observed a reduction of the AI concentrations in the foliar tissues after 48 h of the spraying, evidencing a dissipation process of the AI, after this time. The association of mancozeb to the fungicide (DMI + QoI) only influenced the persistence of PYR at 16 days after spraying in DM 6563 RSF IPRO cultivar. The dissipation rate of PYR is different between the leaves cultivars. The penetration of the AI is greater in younger leaves than in older leaves. The concentrations of PYR in soybean leaves were higher than EPOX at different sampling times, after the fungicide spraying. In the chapter III, it was verified that mancozeb associated with EPOX + PYR in spray solution increases the residual control of P. pachyrhizi and it reduces the disease severity. / A reação de cultivares de soja ao agente causal da ferrugem asiática (Phakopsora pachyrhizi Syd. & P. Syd.) e responsividade de mistura de fungicidas Inibidores da DesMetilação (IDM) e Inibidores da Quinona oxidase (IQo) são importantes fatores a serem determinados para o manejo do patógeno. A atividade desses fungicidas pulverizados na folha depende da quantidade que atinge o local de ação bioquímico e da eficácia do composto. Assim, a proporção do depósito foliar que entra na folha, a taxa de entrada e sua dissipação no tecido foliar são determinantes para a atividade e residual no controle das doenças após a ocorrência de uma lavagem. O capítulo I teve como objetivo avaliar a reação de quinze cultivares de soja ao agente causal da ferrugem asiática e responsividade da mistura dos ingredientes ativos (IA) epoxiconazol (EPOX) + piraclostrobina (PIR) e protioconazol (PROT) + trifloxistrobina (TRIFL). Os parâmetros avaliados foram o período de latência, residual de controle, progresso e a área abaixo da curva de progresso da doença (AACPD). No capítulo II, a persistência de EPOX e PIR associadas com mancozebe (Mz) em duas cultivares comerciais de soja foi determinada em condições de casa de vegetação. Lavagens artificiais foram utilizadas para determinar a concentração dos IA remanescentes nos tecidos foliares após a pulverização. Para isso, as folhas foram lavadas com água 0,17, 1, 2, 4, 48, 96, 192 h após a pulverização do fungicida e imediatamente coletadas. As concentrações de EPOX e PIR também foram determinadas em folhas aos 12, 16 e 20 dias após a pulverização. Através da análise cromatográfica liquida de alta eficiência e do desenho experimental foi possível mensurar as concentrações de EPOX e PIR penetradas e dissipadas em folhas de planta inteira, associadas ou não à mancozebe. A influência da interação de idade de trifólios e cultivares sobre as concentrações de EPOX e PIR após a pulverização também foi avaliada. Devido à escassez de estudos detalhados sobre o desempenho dos fungicidas sítio-específicos associados aos fungicidas multissítios, no capítulo III foi investigado a severidade de ferrugem asiática e o residual de controle da mistura de EPOX e PIR associada ao mancozebe. No capítulo I foi verificado que a responsividade de misturas de IDM e IQo à P. pachyrhizi é distinta entre as cultivares. O maior residual de controle do patógeno nas diferentes cultivares foi através da pulverização de PROT + TRIFL. No capítulo II foi verificado que mancozebe influencia a persistência de fungicidas IDM e IQo em cultivares de soja. A taxa de penetração de EPOX nas cultivares foi mais rápida sem a associação de mancozebe ao fungicida (IDM + IQo). A associação de mancozebe ao fungicida (IDM + IQo) reduziu a taxa de penetração de PIR na cultivar DM 6563 RSF IPRO. A concentração de PIR em folhas das duas cultivares às 48 h após a pulverização foi semelhante pela associação ou não do fungicida com mancozebe. As cultivares apresentaram diferentes taxas de penetração dos IA em folhas. Observou-se uma redução das concentrações dos IA nos tecidos foliares após 48 h da pulverização, evidenciando um processo de dissipação dos IA, após esse tempo. A associação de mancozebe ao fungicida (IDM + IQo) somente influenciou a persistência de PIR aos 16 dias após a pulverização na cultivar DM 6563 RSF IPRO. A taxa de dissipação de PIR em folhas é diferente entre as cultivares. A penetração dos IA é maior em folhas mais novas do que em folhas velhas. As concentrações de PIR em folhas de soja foram superiores que EPOX nos diferentes tempos de coletas, após a pulverização do fungicida. No capítulo III foi verificado que mancozebe associado com EPOX + PIR em calda de pulverização aumenta o residual de controle de P. pachyrhizi e reduz a severidade da doença.

Made available in DSpace on 2017-07-10T17:48:29Z (GMT). No. of bitstreams: 1 Cleiton_Pagliari_Sangali.PDF: 810970 bytes, checksum: 721cfbdc17482672e30e45378a255317 (MD5) Previous issue date: 2012-06-14 / Fundação Araucária / Aiming to assess the relative bioefficacy of DL-2-hydroxy-4-methylthio butanoic acid (DL-HMBA) and of poly-herbal ingredient (PHI) relative to DL-methionine (DLM) in broilers, two experiments were conducted. In the first experiment, 1100 Cobb 500 males and females broilers were fed either, from 1 to 21 days of age with a methionine-deficient basal diet, or the basal diet with three levels (0.170, 0.340, 0.511%) of DL-HMBA or three levels (0.111, 0.221, 0.332%) of DLM in equivalent amount of 65% of the levels of DL-HMBA or still, three levels (0.111, 0.221, 0.332%) of PHI, in equivalent amount the levels of DLM. In the second experiment, 900 Cobb 500 male broilers were fed either, from 22 to 42 days of age with a methionine-deficient basal diet, or the basal diet with three levels (0.143, 0.286 e 0.429%) of DL-HMBA or three levels (0.093, 0.186 e 0.279%) of DLM in equivalent amount of 65% of the levels of DL-HMBA or still, three levels (0.093, 0.186 e 0.279%) of PHI, in equivalent amount the levels of DLM. Simultaneous regression analysis was used to determine the bioefficacy based on weight gain and in feed conversion the of birds of experiments I and II, being that, in experiment II the bioefficacy values were also determined in function of the carcass characteristics of broilers fed with each methionine source. Performance was improved with supplementation of DL-HMBA or DLM in equivalent amount to 65% (DLM-65) of the levels of DL-HMBA, relative to those broilers fed the basal diet. However these responses were not so evident in birds supplemented with PHI. In the first experiment (stage of 1 to 21 days of age), simultaneous linear regression analysis revealed relative bioefficacy of DL-HMBA relative to DLM 39% and 44% for weight gain and feed conversion, on a product basis, respectively, being that, the performance data of birds supplemented with PHI not adjusted the simultaneously regression models, thereby, was not possible determine the bioefficacy of PHI in relation to the DLM. In the second experiment (stage of 22 to 42 days of age), simultaneous exponential regression analysis revealed bioefficacy relative of DL-HMBA and of PHI relative to DLM of 52% and 5% for weight gain and of 57% and 4% for feed conversion, on a product basis, respectively. To breast yield, the simultaneous linear regression analysis revealed relative bioefficacy of DL-HMBA in relation to DLM the 65% on a product basis. The results of this study indicate that the relative bioefficacy of DL-HMBA relative to DLM for broilers in stages of 1 to 21 and from 22 to 42 days old are respectively 42% and 58% on a product basis on average across all criteria tested / Com o objetivo de avaliar a bioeficácia do ácido DL-2-hidróxi-4 (metil) butanoico (DL-HMB) e de um poli ingrediente de ervas (PIE) em relação à DL-metionina (DLM) em frangos de corte foram realizados dois experimentos. No primeiro experimento, 1100 pintos de corte, da linhagem comercial Cobb 500, machos e fêmeas, foram alimentados de 1 a 21 dias de idade com uma dieta basal, deficiente em metionina + cistina, ou a dieta basal suplementada com três níveis (0,170, 0,340, 0,511%) de DL-HMB ou três níveis de DLM (0,111, 0,221, 0,332%) em quantidade equivalente a 65% dos nível de DL-HMB, ou ainda três níveis de PIE (0,111, 0,221, 0,332%), em quantidade equivalente aos níveis de DLM. No segundo experimento, 900 frangos de corte machos da linhagem Cobb 500 foram alimentados dos 22 aos 42 dias de idade com uma dieta basal deficiente em metionina, ou a dieta basal suplementada com três níveis (0,143, 0,286 e 0,429%) de DL-HMB ou três níveis de DLM (0,093, 0,186 e 0,279%) em quantidade equivalente a 65% dos nível de DL-HMB, ou ainda três níveis de PIE (0,093, 0,186 e 0,279%), em quantidade equivalente aos níveis de DLM. A análise de regressão simultânea foi usada para determinar a bioeficácia baseada no peso corporal e na conversão alimentar das aves dos experimentos I e II sendo que, no experimento II os valores de bioeficácia também foram determinados em função das características de carcaça das aves alimentadas com cada fonte de metionina. O desempenho foi melhorado com a suplementação de DL-HMB ou DLM em quantidade equivalente a 65% (DLM-65) dos níveis de DL-HMB, em relação aos frangos alimentados com as dietas basais. No entanto estas respostas não foram tão evidentes nas aves suplementadas com PIE. Para o primeiro experimento (fase de 1 aos 21 dias de idade) a análise de regressão linear simultânea revelou bioeficácia relativa do DL-HMB em relação à DLM de 39% e 44% para ganho de peso e conversão alimentar, em base de produto, respectivamente, sendo que, os dados de desempenho das aves suplementadas com PIE não se ajustaram significativamente aos modelos de regressão simultânea, desta forma não sendo possível determinar a bioeficácia do PIE em relação à DLM. No segundo experimento (fase de 22 aos 42 dias de idade), a análise de regressão exponencial simultânea revelou bioeficácia relativa do DL-HMB e do PIE em relação à DLM de 52% e 5% para ganho de peso e de 57% e 4% para conversão alimentar, em base de produto, respectivamente. Em relação ao rendimento de peito, a análise de regressão linear simultânea revelou uma bioeficácia relativa do DL-HMB em relação à DLM de 65%, em base de produto. Os resultados do presente estudo indicam que a bioeficácia relativa do DL-HMB em relação à DLM para frangos de corte nas fases de 1 aos 21 e dos 22 aos 42 dias de idade são respectivamente de 42% e 58% numa base de produto, em média, em todos os critérios testados

A cada dia cresce o interesse por alimentos ricos em carboidratos não disponíveis em virtude da relação inversa entre seu consumo e o risco de doenças crônicas não transmissíveis (DCNT). No presente trabalho, foi avaliado o potencial fisiológico da farinha de banana verde (FBV) como ingrediente funcional. Em ratos adultos, foi realizado ensaio de média duração (28 dias) para avaliação do efeito trófico da FBV sobre o intestino grosso e de parâmetros relacionados à tolerância à glicose. Em humanos, foram realizados ensaios clínicos de curta e média duração para avaliação dos efeitos sobre resposta glicêmica; liberação de hormônios gastrintestinais relacionados à saciedade; status antioxidante; fome e saciedade; e funcionamento intestinal. A FBV foi produzida com banana verde, Musa acuminata, de acordo com patente depositada pelo grupo (Patente (RPI - 1941), 2008). A FBV é uma fonte concentrada de carboidratos não disponíveis, com 56% de AR e 8% de FAT na base integral. A adição de FBV nas rações provocou efeito trófico no ceco dos animais, evidenciado por aumento no índice metafásico, número de células da cripta e profundidade das criptas. Além disso, a ração com FBV proporcionou melhora nos parâmetros relacionados à tolerância à glicose. Em voluntários saudáveis, a ingestão de uma única refeição adicionada de 8 g de FBV proporcionou aumento na saciedade e boa correlação entre os parâmetros fome/saciedade e níveis plasmáticos de grelina e insulina, melhorou o funcionamento intestinal, além de resultar em alta fermentabilidade in vitro em relação à lactulose. Após ingestão diária da FBV por 14 dias, os resultados da ingestão de RC0 (refeição controle antes do tratamento) e de RC14 (RC0 após 14 dias de tratamento) mostraram que ocorre melhora na tolerância à glicose, evidenciada pela menor liberação de insulina durante o GTT. O efeito positivo sobre funcionamento intestinal, sobre saciedade e sobre liberação de hormônios gastrintestinais no plasma permaneceu após ingestão prolongada da FBV. A adição da FBV na refeição resultou em aumento da capacidade antioxidante in vitro. A FBV apresenta inúmeros atributos positivos para elaboração de produtos que ampliem as opções para uma alimentação saudável, bem como propiciem saúde intestinal, visando a diminuição do risco de DCNT. / The study of unavailable carbohydrates has been of great concern due to their inverse relation with the risk for non-transmissible chronic diseases (NTCD). In the present study, the functional potential of unripe banana flour (UBF) was evaluated. In rats, a medium-term assay was carried in order to evaluate parameters related to glucose tolerance and the trophic effect of UBF on the large bowel. In healthy volunteers, short and medium-term clinical assays were carried to evaluate the effects of UBF on glycemic response; release of gastrointestinal hormones related to satiety (ghrelin, leptin and insulin); antioxidant status; hunger and satiety; and intestinal health. UBF was produced with unripe banana, Musa acuminata, subgroup Cavendish, maturation stage I, in industrial scale and according to a patent deposited by the group (Patent (RPI - 1941), 2008). UBF is a concentrated source of unavailable carbohydrates, with 56% RS and 8% DF (wet weight). Adding UBF in rat rations resulted in a trophic effect in the animals\' cecum, which was evidenced by increase in the metaphasic index, number of crypt cells and crypt depth. Moreover, the ration with UBF resulted in better glucose tolerance parameters. In healthy volunteers, adding UBF (8 g) to an only meal provided significant satiety and good correlation between the parameters hunger/ satiety and plasmatic levels of ghrelin and insulin, improved bowel habit, as well as resulted in high in vitro fermentability in relation to lactulose. After daily intake of UBF for 14 days, the results of the intake of RC0 (control meal before treatment) and RC14 (RC0 after 14 days treatment) showed that there is a positive post-prandial variation in the plasmatic concentrations of gastrointestinal hormones, as well as improvement in glucose tolerance, evidenced by lower insulin release during GTT. The positive effect on bowel habit, satiety and release of gastrointestinal hormones in plasma was kept after prolonged intake of UBF. Adding UBF to the meal provided significant increase in the in vitro antioxidant capacity. UBF presents several positive attributes for the elaboration of products that may increase the options for healthy eating habits, as well as provide intestinal health, always aiming to decrease the risk for NTCD.

Les ventes des fromages AOP subissent un affaiblissement. L’utilisation de ces fromages sous forme d’ingrédient représente une alternative intéressante à la dégustation et permettrait de maintenir une activité durable aux producteurs de ces fromages. L’objectif de ce travail est d’explorer les potentialités de 4 catégories de fromages à pâte persillée AOP du Massif-Central à être utilisés comme ingrédient à chaud pour répondre à des propriétés telles que « fondant, nappant, filant, gratinant». Les fonctionnalités recherchées pour ce type d’usage ont été prospectées à l’aide de méthodes physico-chimiques et instrumentales classiques mais également à l’aide de méthodes spectrales et sensorielles afin d’enrichir les observations de la macro et microstructure fromagère et de la perception du consommateur. Dans un premier temps, les caractéristiques physicochimiques, rhéologiques et sensorielles à froid et certaines propriétés à chaud ont été décrites pour les 4 catégories de fromages. Ces premiers résultats ont permis de cataloguer les fromages selon des caractéristiques essentiellement liées à l’organisation matricielle des composants tels que les protéines, les matières grasses, les minéraux. L’analyse sensorielle a permis de décrire précisément certaines propriétés à froid qui ne sont pas mises en évidence par d’autres analyses. Les pâtes persillées ont une grande hétérogénéité de pâte due à la présence de« veines » de moisissures. La seconde partie est une étude sur la capacité de la SFS en tant que méthode d’étude de la micro structure, à prédire la diversité de composition de ces fromages. Malgré la forte hétérogénéité des fromages, la SFS permet une « empreinte » identifiable des fromages et prédit certains mais pas la totalité des paramètres physicochimiques. L’évolution de la macro et microstructure de ces fromages au cours du chauffage et du refroidissement a ensuite été étudiée par SFS et par test de compression dynamique. Ces méthodes décrivent bien la fonte de la matière grasse et de la matrice fromagère. Elles sont corrélées entre elles et démontrent une relation entre la structure moléculaire et les propriétés rhéologiques de ces fromages. Une étude comparative des propriétés sensorielles des fromages a été menée à froid et après chauffage. Les attributs décrivent des caractéristiques de texture différentes entre les 2 conditions. Cette démarche a permis de bien différencier les 4 catégories de fromages et de mettre en évidence certains attributs de qualité ou de défaut pour une utilisation à chaud. En conclusion, ces 4 catégories de fromages à pâte persillée ont des potentialités à être utilisées comme ingrédient pour usage à chaud. L’analyse sensorielle a caractérisé les perceptions des consommateurs vis à vis de ces fromages chauffés et ainsi aider à préciser leurs fonctionnalités. Les analyses rhéologiques et spectrales ont apporté des explications liées à ce traitement au niveau de la macro et microstructure de la matrice fromagère. / Sales of PDO cheeses undergo a decline. The use of these cheeses in the form of ingredient represents an interesting alternative to the tasting and would allow to maintain a sustainable business activity to the producers of these cheeses. The objective of this work is to investigate the potentialities of four categories of Blue cheese PDO of the Massif Central as an ingredient to meet their properties during heating such as "melting, stretchability, browning". The functional properties desired for this type of cheese have been investigated by physico-chemical methods and instrumental classics and also by spectral method and sensory evaluations to enrich the observations of the macro and microstructure of the cheese and the consumer perception. First, the physicochemical, rheological, sensory characteristics and certain properties during heating have been reported for four categories of Blue cheese. These initial results allowed us to characterize the cheese studied according to their characteristics essentially which were related to the organization matrix constitutes such as proteins, fats, minerals. The sensory analysis allowed to describe exactly certain properties which are not revealed by theother analyses. Blue-veined cheeses have a great heterogeneity due to the presence of "veins" of mold. The second part is a study on the ability of the SFS method to study the micro structure and to predict the diversity of composition of these cheeses. Despite the high heterogeneity of cheeses, SFS allows an identifiable 'fingerprint' of cheese and predicts some but not the totality of the physicochemical parameters. The evolution of the macro-and microstructure of these cheeses during heating and cooling was then studied by SFS and dynamic shear test. These methods describe well the melting temperature of the fat and the cheese matrix. They are correlated between them and demonstrate a relationship between the molecular structure and the rheological properties of these cheeses. A comparative study of the sensory textural properties of cheeses was carried out in the non- and heated forms. The attributes describe different characteristics of texture between the two conditions. This approach allowed to differentiate well the four categories of cheeses and to highlight on certain attributes of quality or defects to be used in cooking application. In conclusion, these four categories of Blue-veined cheeses have the potential to be used as an ingredient in cooking application. The sensory analysis characterized the perceptions of the consumers in both non- and heated forms and thus helps to specify their features. The rheological and spectral analyses have provided explanations related to this treatment at the level of the macro and microstructure of the cheese matrix.

The master's thesis is focused on the posibility of laboratory testing of shotcrete. The important point of the thesis is properties comparison of shotcrete made in laboratory with vibrating press and concrete with the same recipe made by spraying machine. The influence of shotcrete recipe, type and dosage of accelerating ingredient is also examined.

In recent years, companies have increasingly built their businesses around network effects. Furthermore, ingredient branding has become a frequent occurrence in which companies develop their business model by incorporating their product into other products. During contact with the Swedish company Twiceme Technology and after investigating these phenomenon deeper, it appeared to be unique to have both network effects and ingredient branding in the company’s offering. That's where it was discovered a gap in the existing literature and the decision to learn more about how they're related by empirically studying companies that use network effects or ingredient branding in their business models. The overarching aim of the study is to look at characteristics among these phenomenon and analyze how network effects affect ingredient brands, and how they can be connected together. There were several phases in the empirical analysis method. A case sample group of four companies was analyzed in order to obtain a better understanding of the topic in practice. Following that, based on the previous results, the company Twiceme was evaluated as an ingredient brand with network effects. In order to address the research questions, the data extracted from the case sample group and Twiceme were analyzed and compared to theory.  From the study, it was found that achieving a strong market position for network effect companies is highly dependent on reaching the certain network size where the value of the network starts having an exponential increase. High brand equity in terms of brand awareness and reputation is needed to achieve a strong market position accelerated by network effects. Ingredient brands with network effects can generate synergy effects, allowing the network value to potentially grow even faster as a result of the increased brand equity from ingredient branding.  Based on the conclusions of the study and the proposed evaluation framework, this thesis aims to be useful for managerial decision-making and understanding of network effects and ingredient branding, and when they should explore new market opportunities. It also contributes to academia by presenting a novel research perspective in this field and provides material for future research to continue to investigate this subject. / Under de senaste åren har företag i allt högre grad byggt sina företag kring nätverkseffekter. Dessutom har ingrediensvarumärken blivit en vanlig förekomst där företag bygger sin affärsmodell på att integrera sin produkt i andra företags produkter. Under kontakten med det svenska företaget Twiceme Technology och efter att ha undersökt dessa fenomen, påvisades det vara unikt att både vara ett ingrediensvarumärke och ha nätverkseffekter i företagets erbjudande. Där upptäcktes ett gap i den befintliga litteraturen och beslutet att lära sig mer om hur de kan relateras till varandra genom att empiriskt studera företag som använder nätverkseffekter eller ingrediensvarumärkning i sina affärsmodeller. Studiens övergripande mål var att titta på egenskaper hos de bägge och analysera hur nätverkseffekter påverkar ingrediensvarumärken samt hur de kan sammankopplas. Det fanns flera faser i den empiriska analysmetoden. En fallgrupp med fyra företag analyserades för att få en bättre förståelse för ämnet i praktiken. Efter det, baserat på de tidigare resultaten, utvärderades företaget Twiceme som ett ingrediensvarumärke med nätverkseffekter. För att besvara forskningsfrågorna, analyserades data från fallprovgruppen och Twiceme och jämfördes med teorin. Från studien kan det konstateras att uppnå en stark marknadsposition för nätverkseffektföretag är mycket beroende av att uppnå en viss nätverkstorlek där företagets värdeerbjudande börjar öka exponentiellt. För att uppnå en stark marknadsposition som accelereras av nätverkseffekter behövs högt varumärkesmedvetenhet och anseende. Ingrediensvarumärken med nätverkseffekter kan generera synergieffekter, vilket gör att värdeerbjudandet potentiellt kan växa ännu snabbare till följd av det ökade varumärkeskapitalet från ingrediensvarumärken. Baserat på slutsatserna från studien och det föreslagna ramverket, syftar denna uppsats till att vara användbar för ledningsbeslut och förståelsen för nätverkseffekter och ingrediensvarumärkning, samt när de bör utforska nya marknadsmöjligheter. Det ämnar också till att bidra till akademin genom att presentera ett nytt forskningsperspektiv inom detta område och ge material för framtida forskning att fortsätta att undersöka detta ämne vidare.

Les entreprises pharmaceutiques ont progressivement adopté le concept de Process Analytical Technology (PAT) afin de contrôler et d'assurer en temps réel la qualité des produits pharmaceutiques au cours de leur production. Le PAT et un composant central du concept plus général de Quality-by-Design (QbD) promu par les agence régulatrices et visant à construire la qualité des produits via une approche scientifique et la gestion des risques.Une méthode basée sur la spectroscopie proche infrarouge (PIR) a été développée comme un outil du PAT pour contrôler en ligne la cristallisation d'un principe actif pharmaceutique. Au cours du procédé les teneurs en principe actif et en solvant résiduel doivent être déterminées avec précision afin d'atteindre un point d'ensemencement prédéfini. Une méthodologie basée sur les principes du QbD a guidé le développement et la validation de la méthode tout en assurant l'adéquation avec son utilisation prévue. Des modèles basés sur les moindres carrés partiels ont été construits à l'aide d'outils chimiométriques afin de quantifier les 2 analytes d'intérêt. La méthode a été totalement validée conformément aux requis officiels en utilisant les profils d'exactitude. Un suivi du procédé en temps réel a permis de prouver que la méthode correspond à son usage prévu.L'implémentation de cette méthode comme à l'échelle industrielle au lancement de ce nouveau procédé permettra le contrôle automatique de l'étape de cristallisation dans le but d'assurer un niveau de qualité prédéfini de l'API. D'autres avantages sont attendus incluant la réduction du temps du procédé, la suppression d'un échantillonnage difficile et d'analyses hors ligne fastidieuses. / Pharmaceutical companies are progressively adopting and introducing the Process Analytical Technology (PAT) concept to control and ensure in real-time product quality in development and manufacturing. PAT is a key component of the Quality-by-Design (QbD) framework promoted by the regulatory authorities, aiming the building of product quality based on both a strong scientific background and a quality risk management approach.An analytical method based on near infrared (NIR) spectroscopy was developed as a PAT tool to control on-line an API (active pharmaceutical ingredient) crystallization. During this process the API and residual solvent contents need to be precisely determined to reach a predefined seeding point. An original methodology based on the QbD principles was applied to conduct the development and validation of the NIR method and to ensure that it is fitted for its intended use. Partial least squares (PLS) models were developed and optimized through chemometrics tools in order to quantify the 2 analytes of interest. The method was fully validated according to the official requirements using the accuracy profile approach. Besides, a real-time process monitoring was added to the validation phase to prove and document that the method is fitted for purpose.Implementation of this method as an in-process control at industrial plant from the launch of this new pharmaceutical process will enable automatic control of the crystallization step in order to ensure a predefined quality level of the API. Other valuable benefits are expected such as reduction of the process time, and suppression of a difficult sampling and tedious off-line analyzes.