Submitted by Rosivalda Pereira (mrs.pereira@ufma.br) on 2017-06-21T18:41:34Z No. of bitstreams: 1 MarianaArruda.pdf: 2529159 bytes, checksum: 9c046b656b8e783eff46c6684ac9e4b1 (MD5) / Made available in DSpace on 2017-06-21T18:41:34Z (GMT). No. of bitstreams: 1 MarianaArruda.pdf: 2529159 bytes, checksum: 9c046b656b8e783eff46c6684ac9e4b1 (MD5) Previous issue date: 2016-06-30 / Fundação de Amparo à Pesquisa e ao Desenvolvimento Científico e Tecnológico do Maranhão (FAPEMA) / Respiratory infections are leading causes of morbidity and mortality worldwide. The presence of a bacterial etiology generally leads to an intervention with antimicrobial therapy in these infections. Moreover, the abusive and indiscriminate use of antibiotics has produced bacterial resistance, which currently represents a serious public health problem. Thus, natural products may be new therapeutic options to combat drugresistant bacteria. Given the above, this study aimed to investigate the antimicrobial and anti-inflammatory of four plant species: Bixa orellana L. (annatto), Chenopodium ambrosioides L. (American wormseed), Mentha piperita L. (peppermint) and Psidium guajava L. (guava). From the hydroalcoholic extracts of B. orellana (seeds), C. ambrosioides (leaves), M. piperita (leaves) and P. guajava (leaves) in vitro antimicrobial activity was determined by agar diffusion assay, followed by the broth microdilution assay, against seven bacterial strains causing respiratory infections, including: Acinetobacter baumannii, Bordetella pertussis, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pneumoniae and Streptococcus pyogenes. The antimicrobial activity on biofilm formation was evaluated against reference strains of biofilm-producing P. aeruginosa and S. aureus. The most promising extracts were subjected to chemical characterization by high-performance liquid chromatography (HPLC), cytotoxicity, and anti-inflammatory activity test by evaluation of nitric oxide and hydrogen peroxide inhibition as well as their effects on phagocytosis in mice peritoneal macrophages. The tested plant extracts showed antimicrobial activity against at least one of the microorganisms tested. The B. orellana extract showed the highest inhibition zone (16 mm) against S. pyogenes, while the smaller one (8 mm) was found in M. piperita extract against B. pertussis and S. pyogenes. The broth microdilution method was more sensitive, it was demonstrated that extracts of B. orellana, M. piperita, and P. guajava showed activity against all tested pathogens. The lowest inhibitory concentration detected was 0.5 mg/ml P. guajava extract front bacteria P. aeruginosa and S. aureus. P. guajava and B. orellana extracts were able to reduce biofilm formation by P. aeruginosa in 95% and by S. aureus in 93%, both at a concentration of 64 mg/ml. Of the four plant extracts, the one from M. piperita was the most promising, since showed both antimicrobial activity against all the strains studied and the ability to reduce nitric oxide production in macrophages stimulated with LPS. The results indicate a potential of this plant species in the research and development of new antimicrobial agents against the major respiratory pathogens and their associated disease. / As infecções respiratórias são importantes causas de morbidade e mortalidade em todo o mundo. Quando há o envolvimento de uma etiologia bacteriana, os antibióticos são geralmente indicados no tratamento dessas infecções. Por outro lado, o uso abusivo e indiscriminado de antimicrobianos tem propiciado o desenvolvimento de resistência bacteriana, que representa um sério problema de saúde pública. Desta forma, existe a necessidade de investigação de novas alternativas para o controle dessas infecções, como por exemplo, produtos naturais para fins terapêuticos. Diante do exposto, esse estudo teve como objetivo investigar a atividade antimicrobiana e anti-inflamatória de quatro espécies vegetais: Bixa orellana L. (urucum), Chenopodium ambrosioides L. (mastruz), Mentha piperita L. (hortelã) e Psidium guajava L. (goiaba). A partir dos extratos hidroalcoólicos de B. orellana (sementes), C. ambrosioides (folhas), M. piperita (folhas) e P. guajava (folhas) foram realizadas investigação da atividade antimicrobiana in vitro pelo ensaio de difusão em ágar, seguido pela microdiluição em caldo, contra sete cepas bacterianas causadoras de infecções respiratórias, incluindo: Acinetobacter baumannii, Bordetella pertussis, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pneumoniae e Streptococcus pyogenes. A atividade antimicrobiana sobre biofilme foi avaliada contra cepas de referência de P. aeruginosa e de S. aureus produtoras de biofilme. Os extratos que apresentaram melhores atividades foram submetidos a caracterização química pela cromatografia líquida de alta eficiência (CLAE), ensaio de citotoxicidade e avaliação da atividade anti-inflamatória pela dosagem de óxido nítrico e peróxido de hidrogênio, bem como análise da fagocitose em macrófagos peritoneais de camundongo. Os resultados mostraram que os extratos apresentaram atividade antimicrobiana contra, pelo menos, um dos microrganismos testados. O extrato de B. orellana apresentou o maior halo de inibição (16 mm) contra S. pyogenes, enquanto o menor halo (8 mm) foi verificado no extrato de M. piperita contra B. pertussis e S. pyogenes. O método de microdiluição em caldo foi mais sensível, tendo demonstrado que os extratos de B. orellana, M. piperita e P. guajava apresentaram atividade contra todos os patógenos testados. A menor concentração inibitória detectada foi de 0,5 mg/mL do extrato de P. guajava frente as bactérias P. aeruginosa e S. aureus. Os extratos de P. guajava e B. orellana foram os únicos que apresentaram atividade sob a formação de biofilme, principalmente B. orellana com taxas de redução de 95% sob o biofilme formado por P. aeruginosa e de 93% sob o biofilme formado por S. aureus, ambos na concentração de 64 mg/mL. Dos quatro extratos estudados, destaca-se M. piperita, uma vez que apresentou atividade antimicrobiana contra todas as cepas estudadas e também reduziu a produção de óxido nítrico em macrófagos estimulados com lipopolissacarídeo (LPS). Os resultados obtidos indicam o potencial dessa espécie vegetal na pesquisa e desenvolvimento de novos agentes antimicrobianos e anti-inflamatório.

Planejou-se um estudo com o objetivo de se avaliar os níveis plasmáticos de vitamina A, carotenóides e proteína ligadora de retinol (RBP) em 311 crianças, de 7 meses a onze anos de idade, com história de infecções das vias aéreas superiores (IVAS), pneumonia e diarréia, residentes na área urbana da Cidade de São Paulo, Brasil, e atendidas na santa Casa de Misericórdia de São Paulo. As crianças foram classificadas de acordo com seus níveis de vitamina A e carotenóides segundo o critério proposto pelo Interdepartmental Committee on Nutrition for National Defense (ICNND). Para caracterizar estado nutricional das crianças determinou-se o hematócrito e foram realizadas dosagens de hemoglobina e proteinas plasmáticas, medidas antropométricas e avaliação do consumo dietético de alimentos fontes de carotenóides e vitamina A, pelo método da freqüência de consumo alimentar. Os niveis plasmáticos de vitamina A (ug/dl) e RBP (mg/dl) foram mais baixos (p<0,05) nos grupos diarréia e pneumonia (15,2 ug/dl e 1,7 mg/dl; 15,2 ug/dl e 0,7 mg/dl, respectivamente), quando comparados com os grupos IVAS e testemunha (19,0 ug/dl; 2,4 mg/dl e 18,8 ug/dl; 2,6 mg/dl, respectivamente). Os níveis de carotenóides foram mais baixos nos três grupos de estudo em relação ao grupo testemunha (p<0,05). Trinta e quatro pacientes internados do grupo pneumonia foram divididos aleatóriamente, em dois sub-grupos: testemunha (com tratamento de rotina hospitalar) e experimental (tratamento de rotina mais suplementação com 200.000 UI de palmitato de retinila hidromiscível). Após cerca de uma semana da administração de vitamina A, foi verificado aumento estatisticamente significante (p<0,05) nas médias dos niveis de vitamina A (experimental: 26,5 ug/dl; testemunha: 24,1 ug/dl) e RBP (experimental: 2,2 mg/dl; testemunha: 2,9 mg/dl) nos dois grupos, em relação aos niveis basais de vitamina A (experimental: 14,1 ug/dl; testemunha: 16,1 ug/dl) e RBP (experimental: 0,8 mg/dl; testemunha: O, 6 mg/dl)· Não houve diferenças estatísticas quando foram comparadas as médias dos niveis de vitamina A nos grupos experimental e testemunha, após a suplementação (26,5 ug/dl e 24,1 ug/dl, respectivamente). O estudo sugere que os baixos níveis circulantes de vitamina A podem ser conseqüência da reduzida mobilização da vitamina A durante a fase de infecção, devido a baixa disponibilidade de RBP. / The present study was carried out in order to assess the plasma levels of vitamin A, carotenoids and retinol binding protein (RBP) of three-hundred and eleven children aged from seven months to eleven years, who had a history of upper respiratory infection (URI), pneumonia and diarrhoea. The children were resident in the urban area of the Municipality of São Paulo, Brazil, and were seen at the \"Santa Casa de Misericórdia de São Paulo\" Hospital. The Interdepartmental Committee on Nutrition for National Defense (ICNND) criterion was used to classify the children according to their plasma vitamin A and carotenoid levels. Other measurements such as hemoglobin, hematocrit and plasma proteins dosage, anthropometry, as well as vitamin A and carotenoids qualitative intake, evaluated through the food frequency method, were taken in order to characterize the nutritional status of the children. The data shows that plasma vitamin A (ug/dl) and RBP (mg/dl) levels in the diarrhoea (15.2 ug/dl; 1.7 mg/dl) and pneumonia (15.2 ug/dl; 0.7 mg/dl) groups were lower (p<0.05) than those observed in the control (18.8 ug/dl; 2.6 mg/dl) and URI (19.0 J.lg/dl; 2.4 mg/dl) groups. The plasma carotenoid levels were lower in all study groups when compared to the control group (p<0.05). Thirty four hospitalized patients from the pneumonia group were randomly allocated into two groups. The experimental group, besides the routine treatment, received 200.000 UI of aqueous retinyl palmitate oral solution, whereas the control group recei ved only the routine treatment. This clinical trial showed that after one week there was a statistically signif icant (p<0.05) increase in average levels of vitamin A (experimental group: 14.1 ug/dl --> 26.5 ug/dl; control group: 16.1 ug/dl --> 24.1 ug/dl) and RBP (experimental group: O. 8 mg/dl --> 2. 2 mg/dl; control group: 0.6 mg/dl --> 2.9 mg/dl) in both groups as from the baseline. When the final average levels of vitamin A (26.5 ug/dl and 24.1 ug/dl) were compared, any statistically significant difference was found between the groups. This study suggests that low levels of circulating plasma vitamin A maybe a consequence of a reduced mobilization of this vitamin during infectious disease due to low plasma RBP levels.

Thesis (Ph.D.)--University of Alberta, 2010. / A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Doctor of Philosophy, Medical Sciences - Pediatrics. Title from pdf file main screen (viewed on January 24, 2010). Includes bibliographical references.

Respiratory syncytial virus (RSV) infection causes ~64 million cases of respiratory disease and 200,000 deaths annually worldwide, yet there is no broadly effective prophylactic or treatment regimen. RSV can produce acute respiratory illness in patients of all ages but strikes the age extremes, infants and the elderly, with highest frequency presumably due to innate immune deficiencies. A higher morbidity and mortality has been reported for the elderly above 65 years of age, which has been attributed to immune senescence. Efforts to generate an effective vaccine have thus far been unsuccessful. The innate immune system provides the first line of defense against viral pathogens with a repertoire of anatomical barriers, phagocytic immune cells, pattern recognition receptors (PRRs) and antiviral cytokines like interferons (IFNs). The precise mechanism of subversion of innate immunity in young and aged is poorly understood. A better understanding of innate immune pathways is expected to aid in the development of appropriate vaccines or prophylactics for these high-risk groups. Previously, the RSV nonstructural protein 1 (NS1) was shown to antagonize IFN responses by disrupting components of the innate immune system, although the mechanism is not well defined. We hypothesized that NS1 targets constituents of the PRR pathways to evade innate immunity and thus ensure viral survival. Using microscopy and co-immunoprecipitation assays, we found that NS1 localizes to the mitochondria and binds to the mitochondrially associated adaptor protein MAVS, thus preventing MAVS interaction with the RNA helicase, RIG-I. Expression of NS1 was also correlated with upstream IFN-response regulator, LGP2, and its expression was inducible in the absence of a viral infection. Tetracycline-inducible expression of recombinant NS1 in a cell model also promoted viral replication and emphasizes the key contribution of NS1 to RSV survival. Through this study, we demonstrated a mechanism for RSV NS1 in the disruption of early innate responses through mitochondrial localization and alteration of the RLH signaling. Whereas the above studies showed the importance RSV-induced innate immune pathways, whether the expression and signaling of innate immune pathways were adversely affected upon RSV infection in the high-risk groups remains unknown. Since elderly individuals are at an increased risk for severe bronchiolitis and RSV-induced pneumonia, often resulting in hospitalization and medical intervention and adaptive immune cell functionality and responsiveness reportedly decline with age, we hypothesized a similar age-related deterioration of the innate antiviral system. In this investigation, we used an aged mouse model to correlate age-associated changes in innate immune gene expression with RSV pathology. Of 84 antiviral genes examined, five genes including RIG-I, IFNAR1, TLR8, IL-1Β, and osteopontin (OPN) were associated with both age and infection. In response to RSV infection, aged mice had delayed induction of antiviral genes and diminished ability to secrete IL-6 in response to TLR7/8 agonist in primary alveolar macrophages. Lungs from aged, RSV-infected mice had increased cellular infiltration and prolonged infection as compared to young mice. In summary, age-related decline in expression and functionality of antiviral defenses were correlated with enhance RSV-induced lung disease in aged mice. In the absence of infection, aged mice chronically overproduced IL-1Β and OPN relative to young mice. Upon infection, aged mice had impaired ability to secrete higher levels of IL-1Β and mucus. In contrast, OPN secretion remained high and prolonged in aged mice throughout infection. The age-related decline in host antiviral gene induction and delayed cytokine production correlated with enhanced disease pathology. Using a transgenic strain of mice deficient in OPN (OPN-KO), we observed greater resistance to RSV and enhanced secretion of mucus, but unaltered cellular infiltration into the lungs. Therefore, OPN overproduction and defective mucus production likely contribute to pathology in aged mice. These findings demonstrate that RSV targets the innate virus recognition and antiviral cytokine activation pathways but also that the antiviral defense system is significantly affected by age. Consequently, efforts to generate vaccines or develop therapies that stimulate IFN induction may prove unsuccessful in the elderly given that RSV virulence factors and age weaken these responses. This study contributes to our understanding of how aging relates to the RSV subversion of the host antiviral response and should help with the development of better antiviral therapies suited to the growing elderly population.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / Public Health / Master / Master of Public Health

This cross-sectional, community-based study was designed to compare the health outcomes of 2 - 5 year-old children in different types of preschools. The Integrated Child Development Services (ICDS), run by the government of India, created a system of preschools, called anganwadis, to combat malnutrition, provide health education for mothers, and preschool for children 2 - 6 years old in 1975. Many children attend their local anganwadis, while others attend private schools, and others do not attend school at all. A pre-tested questionnaire was used to interview 125 urban and 130 rural mothers regarding their knowledge, attitudes, and practices about acute diarrheal disease (ADD), acute respiratory infections (ARI), and nutrition (practice only) as they pertained to their 2 - 5 year-old child. Two-week and four-week health recalls were obtained to determine which children had experienced diarrhea or ARIs during those time periods. Anthropometric measurements of the children (weight, height, upper-arm circumference) were collected whenever possible. The study was carried out in an urban slum rural villages surrounding in and surrounding Bangalore, India. Data was collected from March through May of 2009. Through data analysis, KAP and child health scores were calculated to compare four preschool types: anganwadis receiving health check-ups from a medical college, anganwadis not receiving the medical check- ups, other (non-anganwadi) preschools and children not attending preschool. Analyses were performed to identify gaps in KAP, determine the impact of KAP on nutritional status, determine the impact of KAP on ADD and ARI, and determine if preschool type influences KAP scores. Children not attending preschool of any type are at higher risk of ADD, ARI, and being underweight. These children have mothers with the lowest attitude scores. Mothers of children in other preschools have the highest percentage of good knowledge and practice scores. Children who attend other preschools also have the lowest prevalence of underweight. This information can be useful in designing interventions for specific populations.

This thesis is based on studies in Butajira district in the south central part of Ethiopia and one study in the Ethio-Swedish Children's Hospital in Addis Ababa. The Butajira project has a continuous demographic surveillance system, established in 1987 in a sample of 10 communities with a total baseline population of about 30,000. The project includes the development and evaluation of a system for continuous registration of vital events and provides a baseline population and sampling frame for health related research activities. The thesis used different study designs within the surveillance system. A carriership study was undertaken to determine the potential bacterial respiratory pathogens among under-five children. A clinical study was done to investigate aetiological agents among young infants (below 3 months) with pneumonia, sepsis and meningitis in a hospital setting. Interview studies were carried out on mothers' perceptions of illness and practices in the care of children with acute respiratory infections. Within the surveillance system, patterns of under-five mortality were analysed. A nested case-referent design was applied to assess public health and behavioural determinants of mortality. A cohort study was performed among under-fives in three communities to estimate the magnitude of illness burden, particularly from ARI, as well as to assess determinants of ARI morbidity. Among 1126 under-five children, 85% were found to harbour H. influenzae, 83% M. catarrhalis and 90% S. pneumoniae in the nasopharynx. The hospital-based study isolated S. pneumoniae, Streptococcus group A, Salmonella group B, E. coli and H. influenzae in the age group below 3 months. The study of mothers' perceptions and practices, showed that mothers do know the symptoms of measles and whooping cough, while they do not recognize pneumonia as an illness entity and are not aware of fast breathing as an important sign of pneumonia. The mortality studies showed a high infant and under-five mortality rate. ARI was responsible for one fifth of the under-five mortality and almost one third of the infant mortality rate. Cause of death in the case-referent study was determined using a validated verbal autopsy method. Breast-feeding and supplementary feeding were demonstrated to be strongly protective when controlling for parental and environmental determinants of mortality. A one year prospective home surveillance study showed that illness was reported in 5.8% of 1,216 person-years. ARI contributed half of this illness load and was particularly associated with parental factors. Among sanitation factors, the absence of piped water was an important determinant of morbidity. Among housing factors, the type of roof and lighting source for the house, and among parental factors, illiteracy of either parents and having a farmer as a father, were found to be independently associated with increased morbidity. Among health and behavioural factors, preterm delivery and lack of immunization were associated with increased morbidity. The results of the studies of this thesis have been utilized to design an intervention case management package. The intervention study and evaluation of its impact is now on-going. / <p>Diss. (sammanfattning) Umeå : Umeå universitet, 1994, härtill 7 uppsatser.</p> / digitalisering@umu.se

This research involved a rigorous implementation of the conceptual framework of Australia's National Strategy for Quality Use of Medicines through a planned sequence of studies across a large defined geographical region to test the hypothesis that: The National Strategy for Quality Use of Medicines can be used to design, implement and evaluate a research program to achieve sustained improvement in health care in a regional setting.

Thesis (M.P.H.M (Primary Health Care Management))--Mahidol University, 2004.