Background: Aceclofenac is a phenylacetic acid derivative with analgesic and anti-inflammatory properties and an improved gastrointestinal tolerance compared with other NSAIDs, such as diclofenac. Objective: This study was conducted to compare the bioavailability of 2 branded formulations of aceclofenac 100 mg (test and reference) marketed in Korea. Methods: This single-dose, randomized, open-label, 2-period crossover study in healthy Korean adult volunteers was conducted at Hanyang University Medical Center (Seoul, Republic of Korea). Subjects received 1 tablet of each aceclofenac 100-mg formulation. Study drugs were administered with 240 mL of water after a 10-hour overnight fast on each of 2 treatment days separated by a 1-week washout period. After study drug administration, serial blood samples were collected over a period of 12 hours. Plasma was analyzed for aceclofenac concentration using a validated high-performance liquid chromatography method with visible detection in the range of 0.1 to 20 μg/mL, with a lower limit of quantitation of 0.1 μg/mL. Several pharmacokinetic (PK) parameters, including Cmax, Tmax, t1/2, AUC0-t, AUC0-∞, and ke, were determined from the plasma concentrations of the 2 aceclofenac formulations. Cmax, AUC0-t, and AUC0-∞ were used to test for bioequivalence after log-transformation of plasma data. The predetermined, regulatory range of 90% CI for bioequivalence was 0.80 to 1.25. Results: A total of 24 subjects were enrolled (20 men, 4 women; mean [SD] age, 23.5 [1.4] years; mean [SD] weight, 68.1 [11.5] kg). No significant differences were found based on analysis of variance, with mean values and 90% CIs of test/reference ratios for these parameters as follows: Cmax, 10.57 versus 9.79 μg/mL (0.961-1.225); AUC0-t, 19.95 versus 19.93 μg · h/mL (0.937-1.037); and AUC0-∞, 20.75 versus 20.48 μg · h/mL (0.949-1.049). Conclusion: In these healthy Korean volunteers, results from the PK analysis suggested that the test and reference formulations of aceclofenac 100-mg tablets were bioequivalent, based on the regulatory definition.

My diploma thesis deals with the optimization and verification of conditions for separation of proteins, which are contained in the twigs of elder (Sambucus nigra L.) using the technique RP-HPLC. The measurements were made with the use of a HPLC system with a UV-VIS detector. Column Zorbax 300SB-C18 300 4,6 x 250 mm and particles the size of 5 microns were used. The theoretical part describes the attributes and usage of elder and especially its proteins. The basic characteristic of the used HPLC technique is introduced. The possibilities of how to identify proteins are described. The practical part demonstrates the individual steps of optimization of the HPLC method applied to the mixture of standard proteins. The application of this method in the real sample is also reported. The final part of the diploma thesis is focused on the comparison of analysed samples taken in different seasons.

Student Number : 9902006N - MSc(Med) Dissertation - School of Medicine - Faculty of Health Sciences / Hepatocellular carcinoma (HCC) is the most common primary malignant tumour of the liver. Aflatoxin B1 (AFB1) is a potent hepatocarcinogen, and dietary iron overload has been shown to contribute to HCC development in black africans. Both are well studied hepatotoxins. The aim of this study was to use a Wistar rat model over a 12 month period to investigate synergy and the extent thereof between AFB1 ingestion and dietary iron overload. 25ug/day of AFB1, reconstituted in DMSO, was administered by gavaging the animals, over a period of 10 days with a 2 day interval in between. The chow diet was supplemented with 0.75% (w/w) ferrocene iron. Experimental subjects were divided into 4 groups. Group 1 was fed the normal chow diet. Group 2 was fed 0.75% (w/w) ferrocene iron alone. Group 3 was gavaged 250μg AFB1 alone. Group 4 was fed the 0.75% (w/w) ferrocene iron and gavaged 250μg AFB1. A number of assays were conducted to investigate synergy. Colorimetric assays were used to measure serum iron, total-iron binding capacity, ALT, AST, GGT, nitrite production, lipid peroxidation and hydroxyproline concentrations. ELISA’s were used to determine ferritin, 8-isoprostane and 8-hydroxyguanosine concentrations. Nontransferrin bound iron was measured using an HPLC method. A chemiluminescent assay was used to measure superoxide anion production. Cytokines were measured using a suspension array system. Mutagenicity was assessed using the Ames mutagenicity assay using salmonella typhimirium strains TA97, TA98, TA100 and TA102. Iron profiling indicated that iron overloading occurred with the ingestion of the ferrocene diet. Biomarkers of oxidative stress, as illustrated by the measurement of 8-hydroxyguanosine and lipid peroxidation, showed additive synergistic effects between the two carcinogens. The anti-inflammatory interleukin-10 was shown to be markedly elevated with the co-administration of the two carcinogens, indicating the elevated inflammatory processes. Additive synergistic effects were noted in terms of the liver disease marker ALT. The salmonella typhimirium strain TA102 used in the Ames mutagenicity test showed increased colony counts with respect to the coadministration of carcinogens (P<0.05), although no synergistic effect was noted. In a few of the presented parameters, the AFB1 group was not significantly different to the control group, although significant differences between the Fe group and the Fe + AFB1 groups were noted. The implication of which is that the presence of AFB1 is increasing the activity of Fe as a carcinogen, thereby acting as a co-carcinogen. Examples of such parameters illustrating this are presented in the results section including serum ALT, serum nitrite, liver and serum lipid peroxidation, liver and serum 8-hydroxyguanosine, some of the mutagenicity assays, and interleukin-10. The conclusion of this study suggests that AFB1 acts as a co-carcinogen in the presence of iron overloading, implying that a synergistic relationship between these two toxins exists.

La tuberculose est une maladie d'urgence dans le monde, l'apparition de souches résistantes au traitement a produit l'utilisation de produits naturels comme alternative. Des études ont montré que les extraits de Leucophyllum frutescens présentaient un effet antimicrobien, mais l'inconvénient est que les extraits sont récupérés dans un véhicule qui contient des solvants organiques. La préparation de nanoparticules polymériques (NP) implique l'élimination du solvant dans lequel l'actif est solubilisé, ce qui permet les utiliser comme véhicules pour l'administration des extraits. Par conséquent, le but de cette étude a été design et développer des formulations de NP avec un extrait de L. frutescens et de la rifampicine (RIF), afin d'évaluer l'activité biologique in vitro contre M. tuberculosis. Premièrement, l'extrait méthanolique de feuilles et de racines de L. frutescens et ses fractions a été obtenu. L'activité contre M. tuberculosis a été déterminée, l'extrait de racines (EMR) et ses fractions hexanique (FHR et RF1) ont été les plus actives avec une CMI de 100, 40 et 40 μg/mL, respectivement. RIF, EMH, FHR et RF1 ont été incorporés dans NP par nanoprécipitation. Des NP de ≈180 nm avec une distribution de taille homogène ont été obtenus. Les NP ont été évaluées sur M. tuberculosis, les formulations de NP-PLGA-RIF (CMI=0,10 μg/mL) et NP-PLGA-RF1 (CMI=80 μg/mL) ont montré la meilleure activité. Finalement, l'activité des formulations combinées contre M. tuberculosis a été évaluée, la combinaison de RIF avec NP-PLGA-RF1 a produit le meilleur comportement, réduisant la CMI des deux sans montrer un effet toxique. Les études réalisées dans ce travail ont montré l'utilisation potentielle d'une formulation de NP contient une fraction végétale de L. frutescens en combinaison avec le RIF comme alternative contre M. tuberculosis / Tuberculosis is an emergency disease worldwide, the emergence of resistant strains to the treatment has produced the use of natural products as alternative. Studies have shown that Leucophyllum frutescens extracts present antimicrobial effect, but the disadvantage is that the extracts are recovered in a vehicle that contains organic solvents. The preparation of polymeric nanoparticles (NP) involves the elimination of the solvent in which the active is solubilized, which makes possible to use them as vehicles for the administration of the extracts. Therefore, the aim of this study was to design and develop formulations of NP with an extract of L. frutescens, and rifampicin (RIF), in order to evaluate the in vitro biological activity against M. tuberculosis. Firstly, the methanolic extract of leaves and roots of L. frutescens and its fractions were obtained. The anti-M. tuberculosis activity was determined, being the root extract (EMR) and its hexane fractions (FHR and RF1) the most actives with a MIC of 100, 40 and 40 μg/mL, respectively. RIF, EMH, FHR and RF1 were incorporated into NP by nanoprecipitation. NP of ≈180 nm with homogeneous size distribution were obtained. The NP were evaluated on M. tuberculosis, being the formulation of NP-PLGA-RIF (MIC=0.10 μg/mL) and NP-PLGA-RF1 (CMI=80 μg/mL) with better activity. Finally, the anti-M. tuberculosis activity of the combined form formulations was evaluated, the combination of RIF with NP-PLGA-RF1 produced better behavior, reducing the MIC of both without showing toxic effect. The studies carried out in this work showed the potential use of an NP formulation contains a vegetable fraction of L. frutescens in combination with RIF as an alternative against M. tuberculosis

Phenolic substances were detected in the celery (Apium graveolens) in three species. Monitoring the phenolics were accomplished in the raw state of the plant, in the plant that was cooked, in the stock and in the dried state. In this master´s thesis are summarized results that were measured, methodology relating to the measurement as well as a description of cultivation of those plants. From the results arise that the smallest amount of phenolic substances has an extract from cooked celery. The biggest amount of phenolic substances is in the raw celery´s stalk as well as in the dried celery. In the celery were identified another three phenolics - Apigenin, Kaempferol, and Lureolin.

Phytoplankton blooms compromise the quality of freshwater ecosystems and the efficient processing of water by treatment works worldwide. This research aims to determine whether in-situ filamentous biofiltration processes mediated by living roots and synthetic filters as media can reduce or remove the phytoplankton loading (micro-algae and cyanobacteria) prior to a potable water treatment works intake. The underlying biofiltration mechanisms were investigated using field and laboratory studies. A novel macroscale biofilter with three plant species, named the "Living-Filter", installed in Farmoor II reservoir, UK, was surveyed weekly for physicochemical and biological variables under continuous flow conditions during 17 weeks. The efficiency of a mesoscale biofilter using the aquatic plant Phalaris arundinacea and synthetic filters, was tested with Microcystis aeruginosa under continuous flow conditions and in batch experiments. The 'simultaneous allelochemical method' was developed for quantifying allelochemicals from Phalaris in aqueous samples. Microscale studies were used to investigate biofilter allelochemical release in response to environmental stressors and Microcystis growth inhibition in filtered and unfiltered aqueous root exudate. Results demonstrate that the removal of phytoplankton biomass by physical mechanisms has a removal efficiency of &le;45% in the "Living-Filter" (filamentous biofilter plus synthetic fabric) and that the removal of Microcystis biomass using only biofilters was 25%. Chemical mechanisms that reduce Microcystis cell numbers are mediated by allelochemicals released from biofilter roots. Root exudate treatments on Microcystis revealed that Microcystis growth is inhibited by allelochemicals, not by nutrient competition, and that protists and invertebrates play a role in removing Microcystis. Filamentous biofilters can remove phytoplankton biomass by physical, chemical and biological mechanisms. Biofilters and synthetic filters in combination improve removal efficiency. Application of macroscale biofilters prior to potable water treatment works benefits the ecosystem. Plant properties, biofilter size to surface water ratio, and retention time must be considered to maximise the benefits of biofiltration processes.