Magister Scientiae - MSc (Pharmacy Administration and Policy Regulation) / Due to inadequacy of data on the effectiveness of medicines regulatory systems in Zambia, this study was framed. The aim was to evaluate legislative provisions for medicines regulation under three legalregulatory- frameworks in place over the period from 1995 to 2015. The study was structured in two distinct phases: the first involved document review of available legislation and secondary data relevant to the subject matter, covering the study period; the second involved a questionnaire survey for health practitioners to gather opinions on the effectiveness of the medicines regulatory systems in Zambia. Assessment of secondary data reported by Ministry of Health, and World Health Organisation on treatment outcomes and medicines regulation was conducted. Reviewed data showed relative reduction in incidence of some selected diseases of national importance. It was also evident that the regulatory systems had improved considerably over the study period. Responses from Health Practitioners and other players in the health and pharmaceutical sectors indicated that they were aware of medicines regulatory requirements, supported the need for medicines regulation, and indicated the need for regional collaboration and increased public awareness raising as means for improving current medicines regulatory systems. It was recommended that more comprehensive studies be undertaken to establish causal relationships between medicines regulatory systems, and disease outcomes. A further recommendation was made to implement more integrated information management systems in the Ministry of Health, and the Zambia Medicines Regulatory Authority.

Pseudomonas aeruginosa is an important pathogen of the immunocompromised, causing both acute and chronic infections. In cystic fibrosis (CF) patients, P. aeruginosa causes chronic disease. The impressive sensory network of P. aeruginosa allows the bacterium to sense and respond to a variety of stimuli found in diverse environments. Transcriptional regulators, including alternative sigma factors and response regulators, integrate signals changing gene expression, allowing P. aeruginosa to cause infection. The two-component transcriptional regulator AlgR is important in P. aeruginosa pathogenesis in both acute and chronic infections. In chronic infections, AlgR and the alternative sigma factor AlgU activate the genes responsible for alginate production. Previous work demonstrated that AlgU controls rsmA expression. RsmA is a posttranscriptional regulator that is antagonized by two small RNAs, RsmY and RsmZ. In this work, we demonstrate that AlgR directly activates rsmA expression from the same promoter as AlgU. In addition, phosphorylation was not necessary for AlgR activation of rsmA using algR and algZ mutant strains. AlgU and AlgR appear to affect the antagonizing small RNAs rsmY and rsmZ indirectly. RsmA was active in a mucA22 mutant strain using leader fusions of two RsmA targets, tssA1 and hcnA. AlgU and AlgR were necessary for posttranscriptional regulation of tssA1 and hcnA. Altogether, our work demonstrates that the alginate regulators AlgU and AlgR are important in the control of the RsmA posttranscriptional regulatory system. These findings suggest that RsmA plays an unknown role in mucoid strains due to AlgU and AlgR activities.

No description available.

No description available.

No description available.

Parmi les plus grandes menaces de la santé publique dans le monde entier, la résistance aux antibiotiques est à la pointe. Ceci en partie est dû à l'augmentation des infections causées par des bactéries pathogènes résistantes aux antibiotiques ainsi que la diminution du nombre actuel de nouveaux antibiotiques. Dans le souci de remédier à cette situation malheureuse, il y a eu récemment la ré-surfaçage des antibiotiques anciens et abandonnés comme les polymyxines. Colistine, un membre des antibiotiques de polymyxine, est maintenant considéré comme un antibiotique de «dernier recours» pour le traitement des infections bactériennes à Gram-négatives graves en raison de son action puissante contre ces agents pathogènes. Cependant, la résistance à la colistine parmi ces agents pathogènes a émergé dans plusieurs pays et est actuellement en augmentation. En raison de la nouvelle réintroduction relative de cet antibiotique, il ya un manque d'information complètes sur ses propriétés pharmacologiques ainsi que des mécanismes par lequel les bactéries développent une résistance contre celle-ci.Afin de combler ce manque d'information en ce qui concerne le mécanisme de résistance, nous avons donc entrepris ce projet. Tout d'abord, pour procéder à une surveillance épidémiologique des bactéries résistantes à la colistine chez les humains et les animaux domestiques et d'autre part, de décrypter les mécanismes moléculaires de résistance à la colistine parmi les bactéries résistantes isolées. / Among one of the greatest threats facing public health worldwide, antibiotic resistance is at the forefront. This is partly due to increase in infections caused by antibiotic-resistant pathogenic bacterial as well as the current dwindling number of new antibiotics. In a way to address this unfortunate situation, there have been recent resuscitation of old and abandoned antibiotics such as polymyxins. Colistin, a member of polymyxin antibiotics, is now regarded as a 'last-resort' antibiotic for the treatment of severe Gram-negative bacterial infections owing to its potent action against these pathogens. However, resistance to colistin among these pathogens has emerged in several countries and is currently on increase. Due to the relatively new reintroduction of this antibiotic, there is a lack of comprehensive information on its pharmacological properties as well as mechanisms by which bacteria develop resistance against it.In order to bridge this information gap in relation to the mechanism of resistance, we therefore undertook this project. First, to carry out an epidemiological surveillance of colistin-resistant bacteria in humans and domesticated animals and secondly, to decipher the molecular mechanisms mediating colistin resistance among the isolated resistant bacteria.

Submitted by Rafaela Moraes (rafaela.moraes@fgv.br) on 2016-09-12T13:53:36Z No. of bitstreams: 1 Dissertação final - Eduardo Nunes - 110911.pdf: 2445774 bytes, checksum: 5a9e59fca83a6a50ff485c12ef6ce047 (MD5) / Approved for entry into archive by Rafaela Moraes (rafaela.moraes@fgv.br) on 2016-09-12T13:54:26Z (GMT) No. of bitstreams: 1 Dissertação final - Eduardo Nunes - 110911.pdf: 2445774 bytes, checksum: 5a9e59fca83a6a50ff485c12ef6ce047 (MD5) / Approved for entry into archive by Rafaela Moraes (rafaela.moraes@fgv.br) on 2016-09-12T13:55:06Z (GMT) No. of bitstreams: 1 Dissertação final - Eduardo Nunes - 110911.pdf: 2445774 bytes, checksum: 5a9e59fca83a6a50ff485c12ef6ce047 (MD5) / Made available in DSpace on 2016-09-12T13:55:45Z (GMT). No. of bitstreams: 1 Dissertação final - Eduardo Nunes - 110911.pdf: 2445774 bytes, checksum: 5a9e59fca83a6a50ff485c12ef6ce047 (MD5) Previous issue date: 2011 / The regulatory system varies depending on the country's institutional endowment. A component of the regulatory system is regulatory governance, namely the set of safeguards that limit discretionary actions of the regulator. In Brazil, one of the safeguards is the institutional design of regulatory agencies. This design consists of a series of factors among which stands out autonomy, commonly divided into administrative, financial and political. The ultimate goal of this study is to evaluate the financial autonomy of federal regulatory agencies. The greater financial autonomy is, the more robust regulatory governance tends to be, because the institutional design plays a better role as safeguard. Strengthened governance contributes to the stability of rules, reduces regulatory risk and enhances the attraction of private investments, which ultimately leverage the country's economic development. To achieve the ultimate goal, it will be held an exploratory, descriptive and explanatory research. The means used are bibliographic, documentary and multiple cases. Each case is selected in a non-probabilistic way by typicality and accessibility, in that order, in order to reach contrasting results (theoretical replication). These criteria determine the choice of all federal regulatory agencies, with the exception of ANAC, because of the accessibility of its budgetary and financial data. Thus, from data of ANEEL, ANATEL, ANP, ANVISA, ANS, ANA, ANTAQ, ANTT and ANCINE for the years 2002 to 2010, four indicators are calculated: budget availability, budget execution, financial execution, and budget and financial overlay. The averages of these partial indicators comprise a comprehensive indicator of financial autonomy. The results are compared between the agencies, between the generations of the agencies and between the sectors of activity of the agencies, using the technique of analysis of variance with a significance level of five percent. The evaluation of the financial autonomy of federal regulatory agencies is unexpected. Rejecting the initial hypotheses, the regulatory agencies of first generation have inferior results to those agencies from second and third generation, and infrastructure agencies have inferior results to social agencies. These results highlight the need to revise the model of budgetary and financial management designed for federal regulatory agencies. The legal provision of own sources of funds is not sufficient to ensure the financial autonomy of agencies to the extent that the central government makes use of increasingly frequent resources impoundments. / O sistema regulatório varia conforme a dotação institucional do país. Um componente do sistema regulatório é a governança regulatória, isto é, o conjunto de salvaguardas que limita ações discricionárias do regulador. No caso brasileiro, uma das salvaguardas é o desenho institucional das agências reguladoras. Este desenho é formado por uma série de elementos entre os quais se destaca a autonomia, comumente dividida em administrativa, financeira e política. O objetivo final deste estudo é avaliar a autonomia financeira das agências reguladoras federais. Quanto maior a autonomia financeira, mais robusta tende a ser a governança regulatória, pois melhor é o papel desempenhado pelo desenho institucional das agências como salvaguarda. Fortalecida, a governança contribui para a estabilidade de regras, reduz o risco regulatório e potencializa a atração de investimentos privados, o que, em última análise, alavanca o desenvolvimento econômico do país. Para alcançar o objetivo final, realiza-se pesquisa exploratória, descritiva e explicativa. Os meios utilizados são bibliográficos, documentais e estudo de múltiplos casos. Cada caso é selecionado de forma não probabilística por tipicidade e por acessibilidade, nesta ordem, a fim de se chegar a resultados contrastantes (replicação teórica). Estes critérios determinam a escolha de todas as agências reguladoras federais, com exceção da ANAC, em virtude da acessibilidade de seus dados orçamentários e financeiros. Assim, a partir dos dados da ANEEL, ANATEL, ANP, ANVISA, ANS, ANA, ANTAQ, ANTT e ANCINE referentes aos anos de 2002 a 2010, são calculados quatro indicadores: de disponibilidade orçamentária, de execução orçamentária, de execução financeira e de sobreposição orçamentária e financeira. As médias aritméticas desses indicadores parciais compõem um indicador global de autonomia financeira. Os resultados encontrados são comparados entre as agências, entre as gerações das agências e entre os setores de atuação das agências, utilizando-se a técnica da análise de variância a um nível de significância de cinco por cento. A avaliação da autonomia financeira das agências reguladoras federais é surpreendente. Rejeitando as hipóteses iniciais, as agências reguladoras de primeira geração obtêm resultados inferiores às agências de segunda e terceira geração, e as agências de infraestrutura resultados inferiores às agências sociais. Estes resultados evidenciam a necessidade de revisão do modelo de gestão orçamentária e financeira concebido para as agências reguladoras federais. A previsão legal de fontes próprias de recursos não é suficiente para assegurar a autonomia financeira das agências na medida em que o governo central faz uso cada vez mais frequente de contingenciamentos de recursos.

No description available.