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Ziel dieser Arbeit war es, die antiinflammatorischen Effekte von Anthocyanen und Anthocyanidinen mit besonderem Augenmerk auf Delphinidin zu vergleichen. Desweiteren sollten im statistischen Vergleich Dosierungen gefunden werden, bei welchen die größte antiinflammatorische Wirksamkeit von Anthocyanen und Anthocyanidinen zu erwarten wäre und ein eventueller Unterschied in der Wirkung der verschiedenen Stoffe berechnet werden. Die Literaturrecherche mittels der Datenbanken „Pubmed“ und „The Cochrane Library“ lieferte 24 Studien, die die Einschlusskriterien erfüllten. Für Delphinidin allein war die Datenlage zu diesem Zeitpunkt noch zu dürftig, weswegen die Suche auf die Begriffe „Anthocyanins“ in Kombination mit „Antiinflammatory Agents“ ausgedehnt wurde. Die statistische Auswertung der Daten erfolgte unter der Fragestellung: „ Haben die Variablen Wirkstoff, Wirkdauer, Menge an Wirkstoff und Art (m-RNA oder Protein“ jeweils unter Kontrolle der anderen Variablen einen Einfluss auf die Reduktion von inflammatorischen Markern?“ Die wichtigsten Ergebnisse, die unter dieser Fragestellung errechnet werden konnten, lauten: 1. PDG zeigt eine bessere antiinflammatorische Wirksamkeit als DP und C3G, 2. Luteolin zeigt eine bessere antiinflammatorische Wirksamkeit als Cyanidin. Gründe für eine höhere antiinflammatorische Wirksamkeit von PDG im Vergleich zu DP und C3G sind derzeit noch offen. Zu diskutieren ist unter anderem, ob DP und C3G biochemisch instabilere Komplexe sind und schneller zerfallen. Grund für eine höhere antiinflammatorische Wirksamkeit von Luteolin im Vergleich zu Cyanidin könnte eine Doppelbindung zwischen C2 und C3 sein, die bei Luteolin, nicht aber bei Cyanidin zu finden ist. In der Zusammenschau dieser Ergebnisse ist festzustellen, dass weitere Studien für eine möglichst genaue statistische Analyse nötig sind, vor allem in Bezug auf die antiinflammatorischen Effekte von Delphinidin. / Aim of this study was to identify antiinflammatory effects of anthocyanins especially of delphinidin. Furthermore we wanted to find the most effectful dosages of anthocyanins and possible differences between the impact of the various substances. Therefore we performed a literally research in June 2012 on Pubmed and Cochrane Library. We found a better efficacy for PDG and Luteolin vs. C3G, Cyanidin and Delphinidin in our statistical analysis. In the synopsis of these findings we determine that further studies are required.

A antitrombina de B. jararaca foi isolada por meio de cromatografia de afinidade em coluna HiTrap Heparin HP (GE Healthcare). A análise da interação da antitrombina humana ou de B. jararaca com a heparina em sistema BIAcoreT200 demonstrou que a antitrombina de B. jararaca apresenta maior afinidade pela heparina que a antitrombina humana. Com relação à sua atividade anti-inflamatória, os resultados obtidos evidenciaram o efeito anti-inflamatório do pré e do pós-tratamento com a antitrombina de B. jararaca na resposta inflamatória aguda. A análise proteômica do exsudato inflamatório de camundongos identificou algumas proteínas possivelmente relacionadas ao mecanismo de inibição da antitrombina, como a enzima C3 do sistema complemento, a sorotransferrina, a a1-antitripsina, a apolipoproteína AI, o fibrinogênio, o cininogênio e a albumina. O processo de clonagem permitiu a obtenção da sequência completa da antitrombina de B. jararaca e apesar da longa distância evolutiva entre serpentes e humanos, diversas características da antitrombina encontram-se conservadas. / B. jararaca antithrombin was isolated by affinity chromatography using HiTrap Heparin HP column (GE Healthcare). The interaction analysis of human or B. jararaca antithrombin with heparin using a BIAcoreT200 system (GE Healthcare) demonstrated that the affinity of B. jararaca antithrombin for heparin is higher than human antithrombin. Regarding the anti-inflammatory activity of B. jararaca antithrombin, the results showed the anti-inflammatory effect of pre- and post-treatment with this molecule in acute inflammation. The proteomic analysis of inflammatory exudate of mice identified some proteins possibly related to the mechanism of inhibition of antithrombin, such as C3 complement, serum transferrin, a1-antitrypsin, apolipoprotein AI, fibrinogen, albumin and kininogen. The molecular cloning process allowed the determination of the complete sequence of B. jararaca antithrombin and despite the evolutionary distance between snakes and human, a number of characteristics are preserved in antithrombin molecule.

Diss. (sammanfattning) Linköping : Linköpings universitet, 2007. / Härtill 5 uppsatser.

Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Michal Čečrle Supervisor: Prof. PharmDr. Petr Pávek, Ph.D. Title of diploma thesis: Introduction of cellular NF-κB model NF-κB is the most important transcription factor involved in cell signaling of inflammatory processes. It participates in the inflammatory reaction in the distinct compartments of the living organism. As a transcription factor, it controls the gene expression of many genes, especially cytokines (tumor necrosis factor alfa, interleukins: IL-1β, IL-2, IL-6, IL-12; chemokines etc.). NF-κB is also a key factor in the activation of monocytes and macrophages In this diploma thesis I focused on the role of NF-κB in the monocyte cell line THP-1. This line is an important model of human macrophages in which the THP-1 line can be differentiated. Using available literature, I summarized all the available knowledge on this issue. At the same time, I conducted several experiments on NF-κB activation in the THP- 1 line as a potential model in the research and development of therapeutic intervention in NF-κB signaling to suppress inflammation.

A antitrombina de B. jararaca foi isolada por meio de cromatografia de afinidade em coluna HiTrap Heparin HP (GE Healthcare). A análise da interação da antitrombina humana ou de B. jararaca com a heparina em sistema BIAcoreT200 demonstrou que a antitrombina de B. jararaca apresenta maior afinidade pela heparina que a antitrombina humana. Com relação à sua atividade anti-inflamatória, os resultados obtidos evidenciaram o efeito anti-inflamatório do pré e do pós-tratamento com a antitrombina de B. jararaca na resposta inflamatória aguda. A análise proteômica do exsudato inflamatório de camundongos identificou algumas proteínas possivelmente relacionadas ao mecanismo de inibição da antitrombina, como a enzima C3 do sistema complemento, a sorotransferrina, a a1-antitripsina, a apolipoproteína AI, o fibrinogênio, o cininogênio e a albumina. O processo de clonagem permitiu a obtenção da sequência completa da antitrombina de B. jararaca e apesar da longa distância evolutiva entre serpentes e humanos, diversas características da antitrombina encontram-se conservadas. / B. jararaca antithrombin was isolated by affinity chromatography using HiTrap Heparin HP column (GE Healthcare). The interaction analysis of human or B. jararaca antithrombin with heparin using a BIAcoreT200 system (GE Healthcare) demonstrated that the affinity of B. jararaca antithrombin for heparin is higher than human antithrombin. Regarding the anti-inflammatory activity of B. jararaca antithrombin, the results showed the anti-inflammatory effect of pre- and post-treatment with this molecule in acute inflammation. The proteomic analysis of inflammatory exudate of mice identified some proteins possibly related to the mechanism of inhibition of antithrombin, such as C3 complement, serum transferrin, a1-antitrypsin, apolipoprotein AI, fibrinogen, albumin and kininogen. The molecular cloning process allowed the determination of the complete sequence of B. jararaca antithrombin and despite the evolutionary distance between snakes and human, a number of characteristics are preserved in antithrombin molecule.

Doctor of Philosophy / Department of Animal Sciences and Industry / Barry Bradford / High levels of milk production has been and will continue to be a priority for the global dairy industry. Non-steroidal antiinflammatory drugs administered to dairy cattle following calving can be an effective way of programming higher milk production for the entirety of lactation. When dairy cattle on a commercial dairy received either sodium salicylate or meloxicam following calving, they responded with increased whole-lactation milk production, which was driven by higher daily milk yields following the seventh week of lactation. When dairy cattle at a research dairy received sodium salicylate following calving, they did not show the same increase in milk production but feed intake, feeding behavior, and blood parameters were altered for an extended period of time. The response to treatment was largely dependent on the parity of the animal. In an effort to determine whether re-programming of the rumen environment could explain these findings, sodium salicylate was administered to batch cultures of rumen fluid, and as a result, fermentation was inhibited. When substrate was fermented in rumen fluid from heifers who had been dosed with sodium salicylate, fermentation was inhibited for an extended period of time following sodium salicylate administration. Beyond the use of compounds such as these, other factors can program lactation for higher milk production, including the gender of the calf. Analysis of lactation records from the US has indicated that cows produce more milk following the birth of a heifer calf compared to a bull. With further research, findings such as these can provide farmers with more tools for improving productivity and lead to the sustainability of the dairy industry as a whole.

Doctor of Philosophy / Department of Animal Sciences and Industry / Barry Bradford / High levels of milk production has been and will continue to be a priority for the global dairy industry. Non-steroidal antiinflammatory drugs administered to dairy cattle following calving can be an effective way of programming higher milk production for the entirety of lactation. When dairy cattle on a commercial dairy received either sodium salicylate or meloxicam following calving, they responded with increased whole-lactation milk production, which was driven by higher daily milk yields following the seventh week of lactation. When dairy cattle at a research dairy received sodium salicylate following calving, they did not show the same increase in milk production but feed intake, feeding behavior, and blood parameters were altered for an extended period of time. The response to treatment was largely dependent on the parity of the animal. In an effort to determine whether re-programming of the rumen environment could explain these findings, sodium salicylate was administered to batch cultures of rumen fluid, and as a result, fermentation was inhibited. When substrate was fermented in rumen fluid from heifers who had been dosed with sodium salicylate, fermentation was inhibited for an extended period of time following sodium salicylate administration. Beyond the use of compounds such as these, other factors can program lactation for higher milk production, including the gender of the calf. Analysis of lactation records from the US has indicated that cows produce more milk following the birth of a heifer calf compared to a bull. With further research, findings such as these can provide farmers with more tools for improving productivity and lead to the sustainability of the dairy industry as a whole.

Este trabalho aborda a espécie Pothomorphe umbellata (L.) Miq. (Piperaceae), conhecida popularmente como pariparoba. Nos últimos anos foram atribuídas diversas atividades a essa espécie, entre elas uma potente atividade antioxidante, atividade anti-inflamatória e ainda inibição in vitro do crescimento de Helicobacter pylori. Tais estudos tornam interessante a investigação da atividade antiúlcera e dos principais grupos de compostos que possam ser relacionados à esta ação, sendo estes os principais objetivos do trabalho. Para cumprir os objetivos propostos, foram utilizados diferentes modelos de ulceração gástrica em animais. Em modelo de indução por etanol acidificado, extratos brutos de folhas e raízes não inibiram significativamente a formação de lesões, porém frações do extrato de raízes conseguiram desempenho semelhante ao do lansoprazol. Em modelo de ligadura do piloro e indução por indometacina o extrato bruto de raízes (EB) não mostrou diferença em relação ao controle negativo. Em modelo de indução por ácido acético, o EB reduziu o tamanho, a presença de necrose e infiltrado inflamatório nas lesões. Com os resultados obtidos, é proposto que sua atividade esteja relacionada à capacidade antioxidante já relatada na literatura. Através de análise e separação por CLAE, foram identificadas três moléculas na fração mais ativa em relação à ação antiúlcera. Duas delas (piperumbellactamas A e B) já haviam sido descritas nessa espécie, porém nas partes aéreas. A terceira (caldensina) havia sido isolada de Piper caldense, e não foram encontrados na literatura relatos de sua ocorrência em P. umbellata. Para melhorar a solubilidade do extrato em água, foi preparada uma suspensão de nanocápsulas, que associou as substâncias mais apolares com sua matriz polimérica. Ao mesmo tempo, formou partículas de tamanho e índice de polidispersão adequados, indicando a viabilidade da formulação. / This work is based on a research of Pothomorphe umbellata (L.) Miq. (Piperaceae) extracts, popularly known as pariparoba. Through the past years, many activities have been attributed to this species, including strong antioxidant activity, anti-inflammatory effect and in vitro growth inhibition of Helicobacter pylori. On that account, the investigation of the antiulcer activity and the research for related chemical compounds was proposed, trying to establish a relationship between these compounds and the activity. To accomplish the proposal, some distinct ulcer models (in rats) were used. The crude extracts from leaves and roots had no significant effect over mucosal damage when tested in acidified ethanol model. By contrast, some fractions from the roots extract showed similar performance when compared to lansoprazole. Also, the crude extract from roots (CE) was not different from water when tested in pylorus ligation and indomethacin induction models. When tested in acetic acid model, the CE significantly reduced the lesion area, the presence of necrosis and inflammatory infiltrate. With these results, a correlation between the antioxidant (previously reported) and antiulcer activities is suggested. The chemical analysis was performed through high-performance liquid chromatography (HPLC) and three molecules were identified in the fraction which showed the stronger antiulcer activity. Two of them (piperumbellactam A and B) had been described in branches of this species. The third (caldensin) had been isolated from Piper caldense, and no record was found about its occurence in P. umbellata. In order to increase CE water solubility, a nanoparticles suspension was prepared. This formulation was able to associate the hydrophobic components to its polymeric matrix. At the same time, it exhibited adequate particle size and polydispersity index, indicating a viability of the formulation.