Dans le cadre d'infections ostéo-articulaire (IOA), l'utilisation de matériels étrangers peut, en cas de contamination, aboutir à la formation d'un biofilm associé à un risque plus important d'échec du traitement et de récidive. Les bactéries sous forme de biofilm sont en effet protégées de l'action du système immunitaire et ont une tolérance plus importante aux antibiotiques. A l'heure actuelle, l'activité des antibiotiques est déterminée par la CMI (Concentration Minimale Inhibitrice), mais cette valeur ne tient pas compte de la forme sessile des bactéries. C'est pourquoi, la société BioFilm Control a développé un nouveau test, l'Antibiofilmogramme®, permettant de déterminer la CMI biofilm (CMIb) reflétant la capacité préventive des antibiotiques sur l'installation des microorganismes en biofilm. L'objectif de ma thèse a été dans un premier temps de participer à la démonstration de la valeur clinique de ce nouveau test dans le cadre des IOA à Staphylococcus aureus. Nous avons pu mettre en place un recueil prospectif et réaliser les premiers essais in vitro. Nos résultats obtenus pour la cloxacillin ont pu par la suite être confirmés sur un modèle in vivo d'infection sur matériel. Dans un second temps, nous avons pu caractériser la capacité de formation de biofilm des souches cliniques en fonction des profils de résistance obtenus en Antibiofilmogramme®. Nous avons pu mettre en évidence des profils différents liés à la clonalité des souches. Enfin, nous avons pu mettre au point une nouvelle méthode de rinçage et de quantification des biofilms pour les modèles en microplaque via l'utilisation de vapeur. Cette approche simple améliore grandement la reproductibilité des résultats et préserve l'intégrité structurelle des biofilms / In the context of Bone and Joint Infections (BJIs), the orthopedic devices are preferential surface for microorganisms to adhere and form biofilm associated with high rates of failures and relapses. Within biofilm, bacteria are protected from the host immune response and are able to survive in the presence of high concentration of antibiotics. The standard Minimal Inhibitory Concentration (MIC) informs on the antibiotic susceptibility of planktonic bacteria, but is not suited for biofilm. The company BioFilm Control developed a new test named Antibiofilmogram® which measures early-stage biofilm growth in presence of antibiotics, and provides a biofilm Minimal Inhibitory Concentration (bMIC). The aim of my PhD research was first to take part in the demonstration of the clinical value of this new test for Staphylococcus aureus BJIs. We established a prospective collection of data and strains and realized the first in vitro assays. Our results for cloxacillin were confirmed in an in vivo model of catheter-associated infection. Second, we characterized the biofilm formation capacity of various clinical isolates based on the Antibiofilmogram® resistance profile. We showed that the biofilm formation capacity is correlated with clonal lineage. Finally, we were able to develop a new method of washing and quantifying biofilms for microplate system using steam. This simple approach preserves the biofilm integrity and lead to highly reproducible data

Corrosion in pipelines and reservoir tanks in oil plants is a serious problem in the energy industries around the world because it causes a huge economic loss due to not only frequent replacements of the parts of pipelines and tanks but also potential damage of the entire fields of crude oil. Previous studies have revealed that corrosions are generated mainly by microbial activities and they are now called as Microbial Influenced Corrosion (MIC) or simply bio-corrosion. Bacterial species actually causing bio-corrosion is crucial for the suppression of the corrosion. To diagnose and give proper treatment to pipelines in industrial plants, it is essential to identify the bacterial species responsible for bio-corrosions. For attaining at this aim, I conducted an analysis of the microbial community at the corrosion sites in pipelines of oil plants, using the comparative metagenomic analysis along with bioinformatics and statistics. In this study, I collected and analyzed various bio-corrosion samples from four different oil fields. First, I collected samples from the seawater pipelines that are essential in the oil fields to maintain seawater injection system (field#1), and then I conducted the metagenomic analysis of these samples. The metagenomes obtained revealed that samples in both sites contain a wide range of bacterial taxa. However, the comparative analysis of the microbial community with statistics in the comparison between sites with corrosion and without corrosion revealed the presence of microorganisms whose abundances were significantly higher in sites with corrosion. Some of these microbes can be sulfate reducers and sulfur oxidizers of which are considered to be casual agents in recent bio-corrosion models. In addition to the seawater pipelines, I also collect samples from corrosion sites in oil pipelines at Field #2 and #3. My metagenomic analysis combined with statistics showed that several microorganisms are speculated to be very active at the corrosion sites in the oil pipeline. Although biological mechanisms of forming bio-corrosion in the oil pipelines still remain unclear, these microbial species are suggested to be some of the responsible bacteria for bio-corrosion in the oil pipelines. Besides seawater injection systems, groundwater injection systems are often used, especially in inland oil fields. Therefore, more detailed understanding of biocorrosion in the groundwater injection system is also required in oil industries. In the present studies, I then analyzed the microbial communities in pipelines in the oil field where groundwater is used as injection water (field #4). I collected samples from four different facilities in the field #4. Metagenome analysis revealed that microbial community structures were largely different even among samples from the same facility. Treatments such as biocide and demineralization at each location in the pipeline may affect the microbial communities independently. The results indicated that microbial inspection throughout the pipeline network is important to protect industrial plants from bio-corrosions. Identifying the bacterial species responsible to bio-corrosion, this study provides us with information on bacterial indicators that will be available to classify and diagnose bio-corrosions. Furthermore, these species may be available as biomarkers to detect the events of bio-corrosion at an early stage. Then, any appropriate care such as the appropriate choice of biocides can be taken immediately and appropriately. Thus, my study will provide a platform for obtaining microbial information related to bio-corrosion that enables us to obtain a practical approach to protect them from bio-corrosion.

This study shows the importance of leading toward missional change within BUSA in post-1994 contexts incorporating global, afro-centric missional perspectives as South African Baptists. As my research will indicate, BUSA is at a crucial junction, and I contend that BUSA’s main problem is primarily a missiological problem, with ecclesiastical challenges that urgently need to be addressed by BUSA’s leaders. The importance of BUSA’s critical self- reflection and analysis is paramount. Does BUSA and her mission have a future, or will it fade into obscurity? Utilizing the South African Baptist faith heritage as an important interlocutor with a view to retrospective and prospective Baptist ecclesiology in post- 1994 South African society. Special recognition is given to the contribution of emerging Afro-centric missional voices within the current South African/African context. In doing so, this study seeks to be leadership-oriented, biblically-based and Afro-centric in its approach to missional change with South African Baptist Union churches. Toward missional leadership within BUSA churches this study: <ul> <li>1. Uncovers the importance of an Afro-centric missional ecclesiology, taking into consideration both local and global trends and conversations.</li> <li>2. Uncover a retrospective view of Baptist Ecclesiology within the Southern African context, with its relevance to the history and present-day context of ministry within BUSA.</li> <li>3. Analyses existing statistical data found within the Baptist Annual Handbook, to establish denominational trends since 1994, with a view to identifying significant ministry trends operable within BUSA.</li> 4. Collects, analyses and interprets data from a number of churches from within the Baptist Union of Southern Africa that stand out as significant in three or more ‘missional indicators’ in the first tier of research and analysis. In reading through the pages to follow, you will journey alongside the researcher in:</li> </ul> <ul> <li> Analysing and interpreting the history of Baptists in South Africa with reference to BUSA, BCSA, SABMS and the ABK through a ‘missional lens’</li>. <li> Critically examining current trends visible within BUSA churches since 1994 to the present-day.</li> <li> Undertaking qualitative research to identify phenomenology of people’s shared experience in BUSA</li> <li> Interpreting and objectifying statistical results drawn from qualitative research at local church level; making further recommendations towards an Afro-centric missional ecclesiology relevant to BUSA churches in post-1994 contexts.</li> </ul> / Thesis (PhD)--University of Pretoria, 2012. / Science of Religion and Missiology / unrestricted

Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical chemistry and Pharmaceutical analysis Author: Petr Šlechta Supervisor: doc. PharmDr. Jan Zitko, Ph.D. Consultant: MSc. Ghada Basem Bouz, Ph.D. Title of diploma thesis: Derivatives combining the fragment of pyrazinamide and 4-aminosalicylic acid as antimycobacterial compounds According to WHO, tuberculosis (TB) is the leading cause of death from a single infectious organism worldwide and the number of cases with drug resistant TB is still increasing, creating the need for new antituberculotics. Therefore, we report design, synthesis and antimicrobial evaluation of a series of hybrid compounds combining different pyrazinamide derivates and p- aminosalicylic acid as potential antituberculotic agents. The compounds were prepared by mixing different pyrazinecarboxylic acids, after activation by 1,1'-carbonyldiimidazole, with p- aminosalicylic acid in dimethylsulfoxide as a solvent. Obtained compounds were in vitro tested for their antimycobacterial activity against M. tuberculosis H37Rv, M. tuberculosis H37Ra and four other mycobacterial strains. Prepared compounds were also in vitro screened for antibacterial, antifungal, and cytotoxic (HepG2) activity. Most compounds showed antimycobacterial activity in range of...

SYNTHESIS AND EVALUATION OF N-PYRIDYLBENZAMIDES AS POTENTIAL ANTIMICROBIAL COMPOUNDS Eliška Suchánková Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic The derivatives of N-pyridylbenzamide were designed and synthesized to be in vitro tested for antimycobacterial activity against Mycobacterium tuberculosis H37Ra, M. smegmatis, M. aurum and in vitro cytotoxicity in HepG2 cells. These compounds are pyridinyl analogues of previously prepared N-pyrazinylbenzamides that have shown a significant in vitro antimycobacterial activity. The title compounds were synthesized by acylation of aminopyridine or chloropyridine-2-amine by selected benzoyl chlorides. Final compounds were described by elementary analysis, melting point, 1 H and 13 C spectra and IR spectroscopy. Generally, prepared compounds possess lower antimycobacterial activity than previously tested N-pyrazinylbenzamides. However, there are some cases, in which the derivatives of pyridine were more effective compared to the derivatives of pyrazine; mainly against M. smegmatis. The best antimycobacterial activity was proved for derivatives of 2-amino-6-chloropyridine and substituted benzoyl chloride, corresponding with higher lipophilicity of these compounds;...

This study was undertaken to compare the MIC (minimum inhibitory concentration) and MPC (mutant prevention concentration) values for oxytetracycline and florfenicol against strains of Pasteurella multocida isolated from cattle and pigs, and for enrofloxacin against strains of Salmonella Typhimurium isolated from horses. Isolates of P. multocida from cattle and pigs, and S. Typhimurium from horses were obtained from specimens or isolates from contributing laboratories. All the equine isolates and 50% of the cattle and pig isolates were from clinically sick animals. All isolates were tested in duplicate with both the MIC and the MPC methods. The MIC method used was the standardized microdilution method performed in microtitre plates. The MPC method used was according to the method described by Blondeau. This method was modified, to make use of smaller plates and lower volumes of antimicrobials, but retaining a final bacterial concentration of 109 colony-forming units per ml. The antimicrobials were dissolved as described in the certificates of analyses. Enrofloxacin and oxytetracycline were dissolved in water, and florfenicol was dissolved in alcohol. For the MPC method, an additional control was added to one quadrant of a four-quadrant 90mm plate/petri dish. The antimicrobials were tested as individual antimicrobials and not as combinations. Both the MIC and MPC methods included ATCC (American Type Culture Collection) strains as control organisms and were evaluated according to the guidelines of the CLSI (Clinical and Laboratory Standards Institute). The MIC50 values for enrofloxacin against Salmonella Typhimurium isolates from horses was 0.25 ìg/ml and the MPC50 values 0.5 ìg/ml. A comparative reference range was not available as enrofloxacin is not registered in South Africa for use in horses, and is used extra-labelly. The results for florfenicol against P. multocida yielded an MIC50 value of 0.5 ìg/ml and an MPC50 value of <2 ìg/ml. The close relationship of these two concentrations is an indication of the effectiveness of florfenicol when used against P. multocida. The PD/PK data with a value of 141.78 for AUC/MIC provided additional support for the efficacy of florfenicol against P. multocida. The PD/PK value of >125, is an effective parameter for treatment of Gram-negative bacteria. The corresponding results for oxytetracycline were above the MIC value but fell within the mutant selection window. The results point to the fact that the use of oxytetracycline against P. multocida may not be effective in preventing the appearance of first step mutant strains when used at current recommended dosages. The PK/PD data, using AUC/MIC, yielded a value of 56. Some of the isolates (55.17%) had an MPC value of 16 ìg/ml. Whereas the MIC method is used routinely in diagnostic laboratories, the MPC method can be employed to generate data that can be applied where antimicrobial treatment of certain bacteria is problematic and standard treatment may lead to the development of resistance. Data obtained from such studies will enable manufacturers of antimicrobial drugs to adapt antimicrobial therapy where practical and feasible to prevent the development of first step mutants. / Dissertation (MSc)--University of Pretoria, 2012. / Veterinary Tropical Diseases / unrestricted

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Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical chemistry and Pharmaceutical analysis Author: Petr Šlechta Supervisor: doc. PharmDr. Jan Zitko, Ph.D. Consultant: MSc. Ghada Basem Bouz, Ph.D. Title of diploma thesis: Derivatives combining the fragment of pyrazinamide and 4-aminosalicylic acid as antimycobacterial compounds According to WHO, tuberculosis (TB) is the leading cause of death from a single infectious organism worldwide and the number of cases with drug resistant TB is still increasing, creating the need for new antituberculotics. Therefore, we report design, synthesis and antimicrobial evaluation of a series of hybrid compounds combining different pyrazinamide derivates and p- aminosalicylic acid as potential antituberculotic agents. The compounds were prepared by mixing different pyrazinecarboxylic acids, after activation by 1,1'-carbonyldiimidazole, with p- aminosalicylic acid in dimethylsulfoxide as a solvent. Obtained compounds were in vitro tested for their antimycobacterial activity against M. tuberculosis H37Rv, M. tuberculosis H37Ra and four other mycobacterial strains. Prepared compounds were also in vitro screened for antibacterial, antifungal, and cytotoxic (HepG2) activity. Most compounds showed antimycobacterial activity in range of...

This thesis entails the design and implementation of a multiple input single output (MISO) DC-DC converter using the flyback topology to charge tablets/ smartphones or any USB powered portable device. The MISO converter will enable the use of various renewable energy sources such as a solar panel/ rechargeable battery combination, bicycle dynamo, hydroelectric power, and wind turbine. This paper will cover the design, simulations, and test results of the MISO converter. The flyback topology was chosen due to its low part count and its efficiency at low power. The proposed converter has a nominal 12V input to output USB 2.0 requirements (5V at 2.5W). Results from both computer simulation using LTSpice and hardware tests demonstrate the functionality of the proposed MISO converter with solar/battery and bicycle dynamo inputs. Overall performance of the converter in terms of efficiency, line and load regulations, as well as its charging ability to a cell phone will be presented in this report.

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