996 resultados para Tuberculosis Vaccines -- administration
Resumo:
ABSTRACT OBJECTIVE To describe the spatial distribution of avoidable hospitalizations due to tuberculosis in the municipality of Ribeirao Preto, SP, Brazil, and to identify spatial and space-time clusters for the risk of occurrence of these events. METHODS This is a descriptive, ecological study that considered the hospitalizations records of the Hospital Information System of residents of Ribeirao Preto, SP, Southeastern Brazil, from 2006 to 2012. Only the cases with recorded addresses were considered for the spatial analyses, and they were also geocoded. We resorted to Kernel density estimation to identify the densest areas, local empirical Bayes rate as the method for smoothing the incidence rates of hospital admissions, and scan statistic for identifying clusters of risk. Softwares ArcGis 10.2, TerraView 4.2.2, and SaTScanTM were used in the analysis. RESULTS We identified 169 hospitalizations due to tuberculosis. Most were of men (n = 134; 79.2%), averagely aged 48 years (SD = 16.2). The predominant clinical form was the pulmonary one, which was confirmed through a microscopic examination of expectorated sputum (n = 66; 39.0%). We geocoded 159 cases (94.0%). We observed a non-random spatial distribution of avoidable hospitalizations due to tuberculosis concentrated in the northern and western regions of the municipality. Through the scan statistic, three spatial clusters for risk of hospitalizations due to tuberculosis were identified, one of them in the northern region of the municipality (relative risk [RR] = 3.4; 95%CI 2.7–4,4); the second in the central region, where there is a prison unit (RR = 28.6; 95%CI 22.4–36.6); and the last one in the southern region, and area of protection for hospitalizations (RR = 0.2; 95%CI 0.2–0.3). We did not identify any space-time clusters. CONCLUSIONS The investigation showed priority areas for the control and surveillance of tuberculosis, as well as the profile of the affected population, which shows important aspects to be considered in terms of management and organization of health care services targeting effectiveness in primary health care.
Resumo:
An in vitro assay system that included automated radiometric quantification of 14CO2 released as a result of oxidation of 14C- substrates was applied for studying the metabolic activity of M. tuberculosis under various experimental conditions. These experiments included the study of a) mtabolic pathways, b) detection times for various inoculum sizes, c) effect of filtration on reproducibility of results, d) influence of stress environment e) minimal inhibitory concentrations for isoniazid, streptomycin, ethambutol and rifampin, and f) generation times of M. tuberculosis and M. bovis. These organisms were found to metabolize 14C-for-mate, (U-14C) acetate, (U-14C) glycerol, (1-14C) palmitic acid, 1-14C) lauric acid, (U-14C) L-malic acid, (U-14C) D-glucose, and (U-14C) D-glucose, but not (1-14C) L-glucose, (U-14C) glycine, or (U-14C) pyruvate to 14CO2. By using either 14C-for-mate, (1-14C) palmitic acid, or (1-14C) lauric acid, 10(7) organisms/vial could be detected within 24 48 hours and as few as 10 organisms/vial within 16-20 days. Reproducible results could be obtained without filtering the bacterial suspension, provided that the organisms were grown in liquid 7H9 medium with 0.05% polysorbate 80 and homogenized prior to the study. Drugs that block protein synthesis were found to have lower minimal inhibitory concentrations with the radiometric method when compared to the conventional agar dilution method. The mean generation time obtained for M. bovis and different strains of M. tuberculosis with various substrates was 9 1 hours.
Resumo:
Nine cases of tuberculosis (TB) were diagnosed among 800 uremic patients, followed-up during 11 years, a prevalence of 1125%, 2.5 times higher than that in the general population. Six patients (66.7%) had lymph node involvement (4 cervical and 2 mediastinal). Three patients (33.3%) had pulmonary involvement (2 pleuro-pulmonary and 1 bilateral apical pulmonary). Eight patients were undergoing dialysis and 1 was pre-dialytic. The duration of dialysis ranged from 1 to 60 months. Three patients had previously received immunosuppressive drugs for unsuccessful renal transplantation. Daily fever was present in all but one patient; he was asymptomatic and TB was suspected after routine chest radiography. Biopsy was the diagnostic procedure in 7 patients (77.8%), four by direct cervical lymph node biopsy, 2 by mediastinal, performed by mediastinoscopy and 1 by pleural biopsy. In 2 other patients TB was confirmed by the presence of tubercle bacilli; in sputum (1 patient) and in a bronchial flushing specimen (the other patient). Triple therapy was used in all patients (isoniazid and ethambutol in all), plus rifampicin in 8 and streptomycin in 1. One patient had jaundice and another had optical neuritis. Five patients were cured. The other four died during treatment of causes unrelated to TB or its treatment.
Resumo:
Tuberculosis (TB) was diagnosed in 25 of 466 patients who underwent renal transplant over a period of 15 years. TB developed from 1 month to 9 years post-transplant. In 56% of the cases the onset was within the first post-transplant year. TB affected several isolated or combined organs. Pulmonary involvement was present in 76% of cases, either as isolated pleuro-pulmonary (56%) or associated with other sites (20%). The non-pulmonary sites were: skin, joints, tests, urinary tract, central nervous system and lymphonodules. The diagnosis was confirmed by biopsy in 64% of the cases, by identification of tubercle bacilli in 24% and only at necropsy in 12% Biopsy specimens could be classified in three histological forms: exudative, that occurred in early onset and more severe cases granulomatous in late onset and benign cases; and mixed in intermediate cases. Azathioprine dosages were similar along post-transplant time periods in TB patients and in the control groups; and in TB patients who were cured and who died. The number of steroid treated rejection crises was greater in TB than in the control group. Prednisone doses were higher and the number of rejection crises was greater in TB patients who died than in those who were cured. Fifteen patients were cured and ten died, two of them of causes unrelated to TB. Six of the eight TB-related deaths occurred in the first 6 post-transplant months. The outcome was poor in patients in whom TB arose early in post-transplant period and where the exudative or mixed forms were present; whereas the prognosis was good in patients with late onset and granulomatous form of TB. In one patient TB was transmitted by the allograft.
Resumo:
Resumo: Os profissionais de sade podem estar expostos a vrios factores indutores de stress crnico nomeadamente de natureza profissional destacando-se, entre os seus possveis efeitos, a diminuio da resposta de anticorpos aps administrao de vacinas, entre as quais, a vacina contra a gripe. Uma vez que os trabalhadores da sade esto expostos a factores indutores de stress e, simultaneamente, a agentes biolgicos cujos efeitos podero ser prevenidos pela vacinao, pertinente estudar a influncia do stress na resposta imunitria vacina contra a gripe em enfermeiros. Constituram objectivos deste trabalho: (1) estudar a associao entre a presena de stress crnico em enfermeiros hospitalares e a insuficiente resposta imunitria vacina contra a gripe, avaliada um ms aps a vacinao (T1); (2) estudar a associao entre a presena de stress crnico em enfermeiros hospitalares e a reduo dos ttulos de anticorpos dirigidos s hemaglutininas seis meses aps a vacinao (T6) e (3) identificar algumas caractersticas das unidades de internamento e do trabalho dos participantes que possam estar associadas presena de stress crnico e estudar a sua possvel associao com a resposta imunitria vacina contra a gripe. Realizou-se um estudo caso-controlo incorporado num estudo de coortes e a amostra em estudo foi constituda por 136 enfermeiros saudveis (83,8% sexo feminino; mdia de idades de 33anos) de um hospital universitrio. Realizaram-se entrevistas individuais e aplicaram-se as verses portuguesas dos questionrios The General Health Questionnaire (GHQ12) e Maslach Burnout Inventory Human Services Survey (MBI-HSS) para determinao da presena de stress crnico pelo mtodo da triangulao, no incio do estudo (T0) e realizou-se a recolha de dados relativos caracterizao de elementos de trabalho nas unidades de internamento. Foi administrada a vacina contra a gripe e determinou-se os ttulos de anticorpos dirigidos s hemaglutininas de cada estirpe componentes da vacina contra a gripe utilizada em 2007, antes da vacinao, um ms e seis meses aps a vacinao. No se encontrou associao, ao nvel de significncia de 5%, entre a presena de stress e a insuficiente resposta vacina contra a gripe, avaliada pela taxa de indivduos que apresentaram um aumento, ao fim de um ms, inferior a quatro vezes os ttulos de anticorpos antes da vacinao. No entanto, encontrou-se uma maior proporo de indivduos com stress no grupo de participantes em que ocorreu uma diminuio do ttulo de anticorpos dirigidos hemaglutinina AH1 (ac AH1) em T6, quando comparado com o respectivo grupo controlo. A diferena entre grupos foi estatisticamente significativa, quando se avaliou a presena de stress pelo mtodo da triangulao usando a entrevista (p=0,006), pelo mtodo da triangulao usando o GHQ12 (p=0,045) e ainda usando a combinao dos trs critrios (p=0,001). Aps anlise multivariada, verificou-se que a associao entre a presena de XXVI stress e a reduo dos ac AH1 em T6 manteve significado estatstico (respectivamente, p= 0,010, p= 0,042 e p=0,002) e apresentou odds ratio ajustados, em funo de cada um dos mtodos de avaliao da presena de stress, de 3,643, de 2,733 e de 5,223. A quantidade de trabalho percepcionada como sobrecarga constituiu o factor indutor de stress mais vezes referido (58,8% da amostra e 61,8% dos enfermeiros de unidades de internamento), seguida dos conflitos entre profissionais. O contacto com o sofrimento e a morte de doentes foram identificados em quarto lugar pela amostra, mas em segundo pelos enfermeiros de unidades de internamento. Nesses, verificou-se uma associao positiva entre trabalhar em Servios onde o nmero de doentes falecidos foi muito elevado e a presena de stress, medido pelo mtodo da triangulao usando a entrevista (p=0,039), usando o GHQ12 (p=0,019), usando a escala de exausto emocional do MBI-HSS (p=0,012) e pela combinao dos trs mtodos (p=0,014). Verificou-se tambm uma associao positiva entre a presena de stress, identificada pelo mtodo da triangulao usando a escala de exausto emocional do MBI-HSS, e o trabalho em servios de internamento onde a percentagem de doentes idosos (p=0,025) e a taxa de letalidade (p=0,036) foram elevadas. Contudo, no se encontrou associao entre a exposio muito frequente ao sofrimento e morte de doentes e a reduo do ttulo de ac AH1 em T6. Possivelmente, a exposio a esse factor indutor de stress, apesar de estar relacionada com a presena de stress nos enfermeiros de servios de internamento, no foi suficientemente intenso para, por si s, estar associada reduo do ttulo de ac AH1 em T6. A associao encontrada entre a presena de stress crnico e a reduo do ttulo de anticorpos AH1 em T6 vem apoiar a resposta questo de investigao inicialmente colocada de que o stress poder influenciar negativamente a manuteno dos ttulos de anticorpos, mesmo em indivduos adultos no idosos. Assim, o risco de um enfermeiro com stress apresentar reduo do ttulo de anticorpos dirigidos hemaglutinina da estirpe AH1N1 A/Solomon Islands/3/2006 ao fim dos seis meses do estudo, foi 3,6, 2,7 ou 5,2 vezes superior ao de um enfermeiro sem stress, consoante o critrio de stress ter sido determinado, respectivamente, pelo mtodo da triangulao usando a entrevista, pelo mtodo da triangulao utilizando o GHQ12 ou pela combinao dos trs critrios. Summary: Health workers may be exposed to various factors causing chronic stress namely those related directly to their activity, in particular the decrease in the capacity of the response of antibodies after the administration of the vaccines, amongst others the Influenza vaccine. Since health workers are exposed to factors causing stress and at the same time biological agents, whose effects may be prevented through vaccination, it is important to study the influence of stress in the immunity response to the Influenza vaccine on nurses. The aims of this study are: (1) to examine the relation between chronic stress in hospital nurses and the insufficient immunity response to the Influenza vaccine, assessed at one month after vaccination (T1); (2) to examine the relation between chronic stress in hospital nurses and the decrease of the hemagglutinin titles of antibodies six months after vaccination (T6); (3) to identify some characteristics of internment units and the work of the participants that may be related to the presence of chronic stress and to study its possible relation with the immunity response to the Influenza vaccine. A control-case study, integrated in a coortes study, was carried out and the sample under analysis consisted of 136 healthy nurses (83,8% female; average age 33 years old) from a university hospital. Several individual interviews were conducted and the portuguese versions of General Health Questionnaire (GHQ12) and Maslach Burnout Inventory Human Services Survey (MBI-HSS) was applied in order to determine the presence of chronic stress, using the triangulation method at the beginning of the study (T0). Data concerning the particular features of the internment units was collected. The Influenza vaccine was administered and the titles of hemagglutinin antibodies of each strain composing the Influenza vaccine used in 2007, before vaccination, and a month and six months after vaccination, were determined. There was no statistically relevant (5%) relation between stress and the insufficient immune response to the Influenza vaccine, according to the rate of individuals that showed, after a month, a level of antibodies concentration lower than four times the level prior to the vaccination. Nevertheless, there was a greater number of individuals with stress in the group of participants in which there was a decrease of the hemagglutinin titles of antibodies AH1 (ac AH1) in T6, when compared to the control group under study. The difference between groups was statistically relevant when assessing the presence of stress by triangulation method using the interview (p=0,006), by triangulation method using the GHQ12 (p=0,045) and by the combination of the three criteria (p=0,001). After multivariate analysis, it was verified that the XXVIII relation between the presence of stress and the reduction of the ac AH1 in T6 was statistically relevant (respectively, p= 0,010, p= 0,042 and p=0,002) and the odds ratio were, according to each of the methods used to assess the presence of stress, 3,643, 2,733 and 5,223. Overwork was the most emphasised stress-causing factor (58,8% of the sample and 61,8% of the nurses working in the Internment Units), followed by conflicts arousing among co-workers. Witnessing the suffering and death of patients was ranked as the fourth cause of stress, but the second by the nurses of the internment units. The former revealed a positive connection between working in the services, where there was a high rate of deaths, and the presence of stress, when assessing the presence of stress by triangulation method using the interview (p=0,039), the GHQ12 (p=0,019), the MBI-HSS emotional exhaustion scale (p=0,012) and by the combination of the three criteria (p=0,014).There was also a connection between the presence of stress, identified by the method of triangulation using the MBI-HSS emotional exhaustion scale, and working in the internment units, where the percentage of elderly people (p=0,025) and the mortality rate (p=0,036) were high. However, there was no connection between frequent exposure to suffering and death in patients and the reduction of ac AH1 titles, in T6. Although one can establish a connection between stress in nurses working in the internment units and the aforementioned stress-causing factor, the exposure to that factor was not, per se, intense enough to reduce the ac AH1 title in T6. The relation found between the presence of chronic stress and the reduction of AH1 antibodies titles in T6, corroborates the hypothesis that stress can negatively influence the title of antibodies, even in non-elderly adults. Thus, and according to the criteria used to define stress, by the triangulation method using the interview, by the triangulation method using the GHQ12 or the combination of the three criteria respectively, the risk of a nurse suffering from stress showing a reduction in the title of hemagglutinin antibodies for the strain AH1N1 A/Solomon Islands/3/2006 six-month after Influenza vaccine was 3,6, 2,7 or 5,2 times greater than on a nurse suffering from no stress at all. Rsum: Les professionnels de la sant peuvent tre exposs diffrents facteurs inducteurs de stress chronique de nature professionnelle. On remarque, parmi les effets possibles, une baisse de la rponse des anticorps aprs ladministration de vaccins, comme en particulier, le vaccin de la grippe. Lorsque les professionnels de la sant ont t exposs des facteurs inducteurs de stress, et de manire simultane, des agents biologiques dont les effets pourront tre prvenus par la vaccination, il est pertinent dtudier linfluence du stress dans la rponse immunitaire au vaccin de la grippe chez les infirmiers. Ils ont constitu des objectifs dtudes et de discussion : (1) tudier lassociation entre la prsence de stress chronique chez les infirmiers, en milieu hospitalier, et la insuffisant rponse immunitaire au vaccin de la grippe, vrifie un mois aprs la vaccination (T1); (2) tudier lassociation entre la prsence de stress chronique chez les infirmiers, en milieu hospitalier, et la rduction de la teneur des anticorps dirig la hmaglutinina six mois aprs la vaccination (T6) (3) identifier certaines caractristiques des units dinternement, et tudier les aspects du travail des participants, qui puissent tre associe la prsence de stress chronique et tudier sa possible association avec la rponse immunitaire au vaccin de la grippe. Une tude cas-contrle incorpore dans une tude de groupe a t ralise et un chantillon, pour tude, a t constitu par 136 infirmiers sains (83,8% de sexe fminin, ge moyen 33 ans) travaillant dans un hpital universitaire. Des entretiens individuels ont t raliss et les versions portugaises des questionnaires de General Health Questionnaire (GHQ12) et Maslach Burnout Inventory- Human Service Survey (MBI-HSS) ont t utiliss pour dterminer la prsence de stress chronique grce la mthode de triangulation, au dbut de ltude (T0) et un relev de donnes relatives la caractrisation dlments de travail dans les units dinternement a t fait. Le vaccin de la grippe a t administr et les teneurs en anticorps dirigs aux hmaglutininas de chaque composant du vaccin de la grippe pour 2007 ont t dtermins, avant la vaccination et un mois et six mois aprs. On na pas trouv dassociation, un niveau significatif de au moins 5%, entre la prsence de stress et la insuffisant rponse au vaccin de la grippe, value par le taux dindividus qui ont prsent une augmentation, la fin du mois, infrieur quatre fois la teneur des anticorps par rapport avant la vaccination. Cependant , on a trouv une plus grande proportion dindividus victimes de stress dans le groupe des participants o il y a eu une baisse de la teneur des anticorps dirig la hmaglutinina AH1 (ac AH1) en T6, aprs comparaison avec le respectif groupe de contrle. La diffrence entre les groupes a t statistiquement significative lorsquon a vrifi la prsence de stress grce la mthode de triangulation, en utilisant lentretien (p=0,006), par la mthode de triangulation en utilisant le GHQ12 (p=0,045) et en utilisant aussi la combinaison des trois critres (p=0,001). Aprs une analyse XXX multivarie, on a vrifi que lassociation entre la prsence de stress et la rduction des ac AH1 en T6 a conserv un signifi statistique (respectivement, p=0,010, p=0,042 et p=0,002) et a prsent des odds ratio ajusts, en fonction de chacune des mthodes de vrification de la prsence de stress de 3,643, de 2,733 et de 5,223. La quantit de travail perue comme une surcharge constitue le facteur inducteur de stress le plus souvent cit (58,8% de lchantillon et 61,8% des infirmiers des units dinternement), suivi par les conflits entre professionnels. Le contact avec la souffrance et la mort des patients a t plac en quatrime position par lchantillon, mais en deuxime position par les infirmiers des units dinternement. Dans ces cas, on a vrifi une association vidente entre le fait de travailler dans des services o le nombre de patients dcds a t trs lev et la prsence de stress, identifie par la mthode de triangulation, en utilisant lentretien (p=0,039), le GHQ12 (p=0,019), lchelle de fatigue motionnelle du MBI-HSS (p=0,012) et en utilisant aussi la combinaison des trois critres (p=0,014). On a aussi vrifi une association positive entre la prsence de stress, identifie par la mthode de triangulation, en utilisant lchelle de fatigue motionnelle du MBI-HSS et le travail dans des services dinternement o le pourcentage de malade gs (p=0,025) et le taux de mortalit ont t levs (p=0,036). Malgr tout, on na pas trouv dassociation entre lexposition trs frquente la souffrance et la mort des patients et la rduction de la teneur de ac AH1 en T6. Probablement lexposition ce facteur inducteur de stress, bien quelle soit lie la prsence de stress chez les infirmiers des services dinternement, na pas t suffisamment intense pour, en elle-mme, tre associe la rduction de la teneur ac AH1 enT6. Lassociation trouve entre la prsence de stress chronique et la rduction de la teneur des anticorps AH1 en T6 vient renforcer lhypothse que le stress pourra influencer ngativement la manutention des teneurs en anticorps mme chez les individus adultes jeunes. Donc le risque quun infirmier stress prsente une rduction de la teneur en anticorps dirigs la hmaglutinina de le composant AH1N1-A/Solomon Island/3/2006 la fin des six mois dtudes a t 3,6, 2,7 ou 5,2 fois suprieure celui dun infirmier sans stress, aprs avoir dtermin le critre de stress, respectivement par la mthode de triangulation utilisant lentretien, par la mthode de triangulation utilisant le GHQ12 ou par la combinaison des trois critres.
Resumo:
Abstract Background: Nanotechnology has the potential to provide agriculture with new tools that may be used in the rapid detection and molecular treatment of diseases and enhancement of plant ability to absorb nutrients, among others. Data on nanoparticle toxicity in plants is largely heterogeneous with a diversity of physicochemical parameters reported, which difficult generalizations. Here a cell biology approach was used to evaluate the impact of Quantum Dots (QDs) nanocrystals on plant cells, including their effect on cell growth, cell viability, oxidative stress and ROS accumulation, besides their cytomobility. Results: A plant cell suspension culture of Medicago sativa was settled for the assessment of the impact of the addition of mercaptopropanoic acid coated CdSe/ZnS QDs. Cell growth was significantly reduced when 100 mM of mercaptopropanoic acid -QDs was added during the exponential growth phase, with less than 50% of the cells viable 72 hours after mercaptopropanoic acid -QDs addition. They were up taken by Medicago sativa cells and accumulated in the cytoplasm and nucleus as revealed by optical thin confocal imaging. As part of the cellular response to internalization, Medicago sativa cells were found to increase the production of Reactive Oxygen Species (ROS) in a dose and time dependent manner. Using the fluorescent dye H2DCFDA it was observable that mercaptopropanoic acid-QDs concentrations between 5-180 nM led to a progressive and linear increase of ROS accumulation. Conclusions: Our results showed that the extent of mercaptopropanoic acid coated CdSe/ZnS QDs cytotoxicity in plant cells is dependent upon a number of factors including QDs properties, dose and the environmental conditions of administration and that, for Medicago sativa cells, a safe range of 1-5 nM should not be exceeded for biological applications.
Resumo:
Abstract The emergence of multi and extensively drug resistant tuberculosis (MDRTB and XDRTB) has increased the concern of public health authorities around the world. The World Health Organization has defined MDRTB as tuberculosis (TB) caused by organisms resistant to at least isoniazid and rifampicin, the main first-line drugs used in TB therapy, whereas XDRTB refers to TB resistant not only to isoniazid and rifampicin, but also to a fluoroquinolone and to at least one of the three injectable second-line drugs, kanamycin, amikacin and capreomycin. Resistance in Mycobacterium tuberculosis is mainly due to the occurrence of spontaneous mutations and followed by selection of mutants by subsequent treatment. However, some resistant clinical isolates do not present mutations in any genes associated with resistance to a given antibiotic, which suggests that other mechanism(s) are involved in the development of drug resistance, namely the presence of efflux pump systems that extrude the drug to the exterior of the cell, preventing access to its target. Increased efflux activity can occur in response to prolonged exposure to subinhibitory concentrations of anti-TB drugs, a situation that may result from inadequate TB therapy. The inhibition of efflux activity with a non-antibiotic inhibitor may restore activity of an antibiotic subject to efflux and thus provide a way to enhance the activity of current anti-TB drugs. The work described in this thesis foccus on the study of efflux mechanisms in the development of multidrug resistance in M. tuberculosis and how phenotypic resistance, mediated by efflux pumps, correlates with genetic resistance. In order to accomplish this goal, several experimental protocols were developed using biological models such as Escherichia coli, the fast growing mycobacteria Mycobacterium smegmatis, and Mycobacterium avium, before their application to M. tuberculosis. This approach allowed the study of the mechanisms that result in the physiological adaptation of E. coli to subinhibitory concentrations of tetracycline (Chapter II), the development of a fluorometric method that allows the detection and quantification of efflux of ethidium bromide (Chapter III), the characterization of the ethidium bromide transport in M. smegmatis (Chapter IV) and the contribution of efflux activity to macrolide resistance in Mycobacterium avium complex (Chapter V). Finally, the methods developed allowed the study of the role of efflux pumps in M. tuberculosis strains induced to isoniazid resistance (Chapter VI). By this manner, in Chapter II it was possible to observe that the physiological adaptation of E. coli to tetracycline results from an interplay between events at the genetic level and protein folding that decrease permeability of the cell envelope and increase efflux pump activity. Furthermore, Chapter III describes the development of a semi-automated fluorometric method that allowed the correlation of this efflux activity with the transport kinetics of ethidium bromide (a known efflux pump substrate) in E. coli and the identification of efflux inhibitors. Concerning M. smegmatis, we have compared the wild-type M. smegmatis mc2155 with knockout mutants for LfrA and MspA for their ability to transport ethidium bromide. The results presented in Chapter IV showed that MspA, the major porin in M. smegmatis, plays an important role in the entrance of ethidium bromide and antibiotics into the cell and that efflux via the LfrA pump is involved in low-level resistance to these compounds in M. smegmatis. Chapter V describes the study of the contribution of efflux pumps to macrolide resistance in clinical M. avium complex isolates. It was demonstrated that resistance to clarithromycin was significantly reduced in the presence of efflux inhibitors such as thioridazine, chlorpromazine and verapamil. These same inhibitors decreased efflux of ethidium bromide and increased the retention of [14C]-erythromycin in these isolates. Finaly, the methods developed with the experimental models mentioned above allowed the study of the role of efflux pumps on M. tuberculosis strains induced to isoniazid resistance. This is described in Chapter VI of this Thesis, where it is demonstrated that induced resistance to isoniazid does not involve mutations in any of the genes known to be associated with isoniazid resistance, but an efflux system that is sensitive to efflux inhibitors. These inhibitors decreased the efflux of ethidium bromide and also reduced the minimum inhibitory concentration of isoniazid in these strains. Moreover, expression analysis showed overexpression of genes that code for efflux pumps in the induced strains relatively to the non-induced parental strains. In conclusion, the work described in this thesis demonstrates that efflux pumps play an important role in the development of drug resistance, namely in mycobacteria. A strategy to overcome efflux-mediated resistance may consist on the use of compounds that inhibit efflux activity, restoring the activity of antimicrobials that are efflux pump substrates, a useful approach particularly in TB where the most effective treatment regimens are becoming uneffective due to the increase of MDRTB/XDRTB.
Resumo:
Apresentao realizada na Conferncia "Changing Public Sevice in a Changing World" realizada em Budapeste a 24 de Abril de 2009
Resumo:
Apresentao realizada no INA por ocasio da visita de uma delegao da Repblica da Srvia a Portugal.
Resumo:
Apresentao realizada a uma delegao da Administrao pblica da Bulgria, que visitou o INA em 2 de Dezembro de 2008.
Resumo:
Comunicao apresentada na 32 conferncia anual do European Group of Public Administration (EGPA), em Toulouse.
Resumo:
Apresentao realizada no OH&S Forum 2011 - International Forum on Occupational Health and Safety: Policies, profiles and services, na Finlndia de, 20 a 22 Junho de 2011.
Resumo:
Poster apresentado na 8. Conferncia da European Academy of Occupational Health Psychology, em Valencia, 12-14 de novembro de 2008.
Resumo:
Apresentao realizada na LivingAll European Conference, em Valncia, Espanha, de 15-16 janeiro de 2009
Resumo:
Comunicao apresentada na 69th ASPA Anual Conference, em Dalas, Texas de 7 a 11 de maro de 2008
