CoordenaÃÃo de AperfeiÃoamento de NÃvel Superior / A doenÃa de Chagas (DC) à considerada negligenciada sob vÃrios aspectos, dentre eles, por ser uma doenÃa que atinge pessoas de baixo nÃvel socioeconÃmico, pela falta de investimento em pesquisas para conhecer seu real panorama de prevalÃncia e pela limitada efetividade dos medicamentos disponÃveis. O presente estudo avaliou a soroprevalÃncia da infecÃÃo chagÃsica e o perfil sociodemogrÃfico de indivÃduos residentes no municÃpio de Limoeiro do Norte â CE, no perÃodo de abril a novembro de 2013. O estudo soroepidemiolÃgico foi realizado em 812 indivÃduos selecionados de forma aleatÃria incluindo habitantes locais, de ambos os sexos, com idade a partir de dois anos. Para atender aos objetivos, empregou-se o teste ELISA para pesquisa de anticorpos IgG anti-Trypanosoma cruzi e um questionÃrio semiestruturado para traÃar o perfil sociodemogrÃfico. As variÃveis do questionÃrio foram analisadas, por meio dos testes qui-quadrado ou exato de Fisher. Foram analisados 812 indivÃduos, dentre os quais 4,2% (34) apresentaram sorologia reagente para DC. As variÃveis sociodemogrÃficas que apresentaram associaÃÃo significativa com positividade para DC foram: idade maior que 50 anos (RP= 27,6; IC= 6,66-114,4; p= 0,000); escolaridade atà ensino fundamental incompleto (RP= 5,15; IC= 1,83-14,47; p= 0,000) e ocupaÃÃo aposentado (RP= 7,25; IC= 3,72- 14,14; p= 0,000). As condiÃÃes atuais de moradia dos participantes diagnosticados com infecÃÃo chagÃsica foram semelhantes Ãs dos nÃo infectados. A positividade para DC foi 6,17 vezes maior no grupo daqueles que jà residiram em casas de taipa (IC= 2,19â17,37). NÃo houve transmissÃo vertical nos indivÃduos estudados, uma vez que nenhum dos participantes, com mÃe chagÃsica, foi reagente para anticorpos anti-T. cruzi. NÃo houve associaÃÃo entre transfusÃes e positividade, indicando, que a transmissÃo se deu, possivelmente, por via vetorial nessa Ãrea. Dentre os indivÃduos infectados com T. cruzi, a maioria relatou ter algum problema de saÃde (p=0,000), sendo que a hipertensÃo arterial sistÃmica foi à Ãnica comorbidade, dentre as citadas, que mostrou associaÃÃo com a DC (p=0,000). Os indivÃduos com sorologia positiva predominaram, de maneira significativa, entre aqueles que vÃo mais de duas vezes ao mÃdico por ano (p=0,000) e que realizam algum tipo de exame com frequÃncia (p=0,025). Esse estudo possibilitou conhecer a soroprevalÃncia da infecÃÃo chagÃsica, o perfil sociodemogrÃfico dos infectados, verificar as variÃveis que tiveram associaÃÃo significativa com DC e beneficiar indivÃduos com o diagnÃstico precoce na fase crÃnica da infecÃÃo para que possam receber cuidados especÃficos. / Chagas disease (CD) is considered neglected in many aspects, among them, for being a disease that affects people of low socioeconomic status, for the lack of investment in research to characterize the real picture of its prevalence and for the limited effectiveness of available drugs. The present study evaluated the seroprevalence of T. cruzi infection and the sociodemographic profile of people living in the city of Limoeiro do Norte - CE in the period from April to November, 2013. The seroepidemiological study was conducted in 812 randomly selected individuals including local people of both sexes, aged at least 2 years. To meet the objectives, we used the ELISA test for IgG anti-Trypanosoma cruzi antibodies and a semi-structured questionnaire to find the sociodemographic profile. Questionnaire variables were analyzed using the chi-square or Fisher exact test. From the 812 individuals anlyzed, 4.2% (34) were seropositive for CD. The following sociodemographic variables were significantly associated with seropositivity for CD: age greater than 50 years (OR = 27.6, CI = 6.66 to 114.4, p = 0.000); incomplete primary education (PR = 5, 15 CI = 1.83 to 14.47, p = 0.000) and retired occupation (PR = 7.25, CI = 3.72 to 14.14, p = 0.000). The current housing conditions of the participants diagnosed with Chagas disease were similar to those uninfected. Seropositivity for CD was 6.17 times higher in the group of those who have lived in mud houses (CI = 2.19 to 17.37). There was no vertical transmission in the subjects studied, since none of the participants with Chagas-infected mother was reactive for anti-T. cruzi. There was no association between transfusions and seropositivity, indicating that vectorial transmission possibly occurred in this area. Among individuals infected with T. cruzi, most reported having at least one health problem (p = 0.000), and hypertension was the only comorbidity out of those cited that showed association with CD (p = 0.000). There was a significant predominance of seropositivity among those individuals that go to the doctor more than twice a year (p = 0.000) and perform some kind of test frequently (p = 0.025). This study brought us the seroprevalence of T. cruzi infection, the sociodemographic profile of those infected and the characteristics that were significantly associated with CD. Furthermore, the study allowed us to benefit individuals with early diagnosis in the chronic phase of the infection, so that they can receive specialized care.

The American Visceral Leishmaniasis (AVL) is endemic in tropical and subtropical regions of Latin America. In Brazil, in recent years has been expanding and building up. Historically, the state of Ceara has been presented in several cities a high prevalence of the disease, however, the city of Fortaleza, escaping this epidemiological pattern always reported low incidence of the disease, however, from 2005, showed an increase in the number of cases and spatial distribution, showing an expanding epidemic of the disease. The aim of this study was to evaluate the spatial and temporal distribution of disease incidence in the period 1995 to 2008. We analyzed the cases of AVL reported in SINAN and SIM, considering only patients in Fortaleza, who met the criteria adopted by the Ministry of Health for confirmation of diagnosis and the site of infection. The cases were georeferenced and analyzed based on the indicators: incidence and mortality and the following variables: dependent - confirmed cases of the disease and independent - age, age group, sex, place of residence, clinical manifestation, clinical course and type of diagnosis. We used spatial analysis techniques to analyze the cases. During the study period were recorded human cases of AVL 1267, of which 50% were younger than 4 years and 74 deaths. The year 2007 was presented the highest incidence of the disease. The highest incidence of cases were in males (64.3%). The average age of cases of AVL increased in epidemic period. The disease is clinically expressed differently in the epidemic phase, compared with the endemic phase. The risk of infection was higher in males than in females. Mortality was high only in the age group above 60 years. There was a significant increase in disease incidence in the elderly. Diagnostic tests showed high sensitivity and specificity. Over 70% of cases were confirmed through laboratory tests. We observed a decrease in cure rate and an increase in cases of co-infection with HIV. In the epidemic phase, spatial diffusion of disease was the kind of contagion. The diffusion process was linked to environmental factors and socioeconomic factors. We identified areas of high risk for the disease occurrence based on spatial analysis techniques. The study revealed the establishment of a new epidemiological pattern for kala-azar in Fortaleza, mainly characterized by the appearance of an emerging problem: the increase of cases of co-infection with HIV. Also revealed that environmental factors and socioeconomic factors were crucial in the processes of urbanization and expansion of the disease in the city. / A Leishmaniose Visceral Americana (LVA) à uma doenÃa endÃmica nas regiÃes tropicais e subtropicais da America Latina. No Brasil, nos Ãltimos anos, vem se expandindo e urbanizando-se. Historicamente, o Estado do Cearà tem apresentado, em diversos municÃpios, altas prevalÃncias da enfermidade; entretanto, a cidade de Fortaleza, fugindo desse padrÃo epidemiolÃgico sempre registrou baixa ocorrÃncia da doenÃa, no entanto, a partir de 2005, apresentou incremento significativo no nÃmero de casos e na distribuiÃÃo espacial, evidenciando uma expansÃo epidÃmica da doenÃa. O objetivo deste estudo foi avaliar a distribuiÃÃo espacial e temporal da incidÃncia da doenÃa, no perÃodo de 1995 a 2008. Foram analisados os casos de LVA notificados no SINAN e no SIM, considerando-se apenas os pacientes residentes em Fortaleza, que preenchiam os critÃrios adotados pelo MinistÃrio da SaÃde para confirmaÃÃo diagnÃstica e do local da infecÃÃo. Os casos foram georreferenciados e analisados com base nos indicadores: taxa de incidÃncia e letalidade e nas seguintes variÃveis: dependente â casos confirmados da doenÃa e independentes â sexo,faixa etÃria, grupo etÃrio, local de residÃncia, manifestaÃÃo clÃnica, evoluÃÃo clÃnica, tipo de diagnÃstico, tipo de tratament e escolaridade. Foram utilizadas tÃcnicas de anÃlise espacial para analisar os casos. No perÃodo do estudo foram registrados 1.267 casos humanos de LVA, dos quais 50% eram menores de 4 anos, e 74 Ãbitos. O ano de 2007 foi o que apresentou a maior taxa de incidÃncia da doenÃa. A maior ocorrÃncia de casos foi em indivÃduos do sexo masculino (64,3%). Houve mudanÃa de perfil da idade e da forma de expressÃo clÃnica da doenÃa na fase epidÃmica, comparada com a fase endÃmica. O risco de adoecer no sexo masculino foi maior do que no sexo feminino. A letalidade foi alta apenas na faixa etÃria acima dos 60 anos. Houve um crescimento significativo na incidÃncia da doenÃa em pessoas idosas. Os exames diagnÃsticos apresentaram alta sensibilidade e especificidade. Mais de 70% dos casos foram confirmados por critÃrio laboratorial. Foi observada uma queda na taxa de cura e um aumento dos casos de co-infecÃÃo por HIV. Na fase epidÃmica, a difusÃo espacial da doenÃa foi do tipo por contÃgio. O processo de difusÃo esteve associado aos fatores ambientais e socioeconÃmicos. Foram identificadas as Ãreas de alto risco para a ocorrÃncia da doenÃa com base nas tÃcnicas de anÃlise espacial. O estudo revelou o estabelecimento de um novo padrÃo epidemiolÃgico para o calazar em Fortaleza, caracterizado principalmente pelo surgimento de um problema emergente: o incremento de casos de co-infecÃÃo por HIV. Revelou, ainda, que os fatores ambientais e socioeconÃmicos foram determinantes nos processos de urbanizaÃÃo e expansÃo da doenÃa na cidade.

A endometrite é a causa mais importante de infertilidade em éguas falhadas e inflige grandes perdas na indústria de criação de equinos. Infecções uterinas bacterianas podem ocorrer em 25 % a 60 % das éguas estéreis e os agentes patogênicos mais frequentemente isolados são Streptococcus zooepidemicus e Escherichia coli. A endometrite causada por Streptococcus sp tem sido amplamente estudada, no entanto, pouco se sabe sobre a resposta endometrial da égua à E. Coli. Infecção focal induzida por E. coli foi associada com resposta inflamatória uterina menos exsudativa do que infecção por Streptococcus zooepidemicus. Em contrapartida, alguns estudos têm mostrado que as infecções uterinas por E. coli foram menos propensos a ter evidência citológica de inflamação. O objetivo deste estudo foi descrever a resposta inflamatória após a inoculação intra-uterina com três diferentes cepas de E. coli na égua. Nove éguas cíclicas , com idades entre 7 e 20 anos, foram selecionadas e seu estro detectado por palpação transretal e ultrassom. Somente éguas clinicamente normais com citologia negativa e bacteriologia foram utilizadas no experimento. Três diferentes cepas de E. coli obtidas a partir de: (UT) swab uterino de uma égua com endometrite, (VE) swab do vestíbulo de uma égua saudável e (FE) a partir de fezes de égua, foram utlizadas. Subsequentemente , as éguas foram submetidas a inoculação intrauterina com 3x109de bactérias de uma das três diferentes cepas E. coli. Todas as éguas foram desafiadas com as três cepas de E. coli de forma aleatória nos ciclos subseqüentes. Um dia após a infecção, foram realizados exame clínico do trato genital por espéculo, ultrassonografia, citologia endometrial e cultura bacteriológica. Estes procedimentos foram repetidos diariamente até ser diagnosticado cultura bacteriana e citologia negativa. Todas as éguas tiveram leve (<10/campo ) a grave (> 20/campo) neutrofilia endometrial 24h após a inoculação de E. coli. Em 25 das 27 infecções ( 92,6 %), sinais clínicos vaginais e líquido intra-uterino (LIU) foram detectados. Sinais clínicos vaginais graves como aspecto purulento e mucosa hiperêmica foram observadas em 17 infecções e 8 apresentaram sinais leves. Apenas 59,2% das infecções experimentais (16/27) foram positivas à cultura para E. coli 24h após a infecção. O tempo necessário para a eliminação das bactérias foi, em média de 2,8 dias ( ± 1,0 ). O tempo para o desaparecimento da inflamação (presença de leucócitos polimorfonucleares) foi em média 3,4 dias (±0.8). Em conclusão, a endometrite causada por E. coli provocou citologia positiva e a maioria das éguas desenvolveram sinais clínicos vaginais de endometrite e acúmulo de liquido intrauterino, não havendo diferença entre as cepas de E. coli. / Endometritis is the most important cause of infertility in barren mares and inflicts major losses on the equine breeding industry. Bacterial uterine infections occur in 25% to 60% of barren mares and the most frequently isolated pathogens are Streptococcus zooepidemicus and Escherichia coli. Endometritis caused by Streptococcus sp has been widely studied. However, little is known about the mare’s endometrial response to E. coli. Focal infection induced by E. coli was associated with less exudative uterine inflammatory response than by Streptococcus zooepidemicus. In contrast some studies have shown that uterine infections by E coli were less likely to have cytological evidence of inflammation. Treatment of mares with persistent uterine infections needs to be directed towards the underlying breakdown of the uterine defense and against the microbial agent. The aim of this study was to describe the inflammatory response after intrauterine inoculation with three different strains of E. coli in the mare. Nine cyclic mares aged between 7 and 20 years old were selected and their estrous detected by transrectal palpation and ultrasound. Only clinically normal mares with negative cytology and bacteriology were used. Three different strains of E. coli obtained from: (UT) uterine swab of a mare with endometritis, (VE) vestibular swab from a healthy mare and (MA) from mare manure, were used. Subsequently, the mares were submitted to intrauterine inoculation with 3x109 E. coli of one of the three different strains. All mares were challenged with each strain of E. coli in a randomized order in the subsequent different cycles. One day after infection, clinical examination of the genital tract by speculum, ultrasound, endometrial cytology and bacteriological cultures were performed. These procedures were repeated daily until negative culture and negative cytology were diagnosed. All mares had slight (<10/field) to severe (> 20/field) endometrial neutrophilia 24h after E. coli inoculation. In 25 of 27 infections (92.6%), vaginal clinical signs and intrauterine fluid (IUF) were detected. Severe vaginal signs with purulent aspect and hyperemic mucosa were observed in 17 infections and 8 presented mild signs. Only 59.2% of the examinations (16/27) were E. coli positive 24h after the infection. The time needed for elimination of bacteria in mares treated with leukocytes and mares of control group was in average 2.8 days and the cytology remained positive 3.4 days in average. In conclusion, E. coli endometritis provoke a positive cytology and most of the mares developed vaginal clinical signs of endometritis and IUF, with no difference among E. coli strains.

No description available.

No description available.

No description available.

No description available.

Translational control has a direct impact on cancer development and progression. Quantitative and qualitative changes of cap-dependent translation initiation contribute to neoplastic transformation and progression. However, the idea that “alternative” mechanisms of translation initiation, such as IRES-dependent translation, can be involved in the tumorigenesis is emerging. Because the relevance of this kind of translation initiation in cancer progression is not so well clarified, the purpose of my work was to study the impact of IRES-dependent mRNA translation on tumourigenesis and cancer progression with particular regard for breast cancer. The data obtained clarify the function of cap-independent translation in cancer. Particularly they suggested that the deregulation of IRES-dependent translation can be considered a sort of pro-oncogenic stimulus characterized by the inhibition of the expression of some proteins that block cell growth and proliferation and by the over expression of other proteins that contributed to cell survival. In addition, under stress condition, such as a hypoxia, in immortalized epithelial cell lines, changes in cap-independent translation are associated with an induction of expression of stem cell markers, and with the selection of a sub group of cells that have an increased ability to self-renewing and therefore in the acquisition of a more aggressive phenotype.

In cycling cells positive stimuli like nutrient, growth factors and mitogens increase ribosome biogenesis rate and protein synthesis to ensure both growth and proliferation. In contrast, under stress situation, proliferating cells negatively modulate ribosome production to reduce protein synthesis and block cell cycle progression. The main strategy used by cycling cell to coordinate cell proliferation and ribosome biogenesis is to share regulatory elements, which participate directly in ribosome production and in cell cycle regulation. In fact, there is evidence that stimulation or inhibition of cell proliferation exerts direct effect on activity of the RNA polymerases controlling the ribosome biogenesis, while several alterations in normal ribosome biogenesis cause changes of the expression and the activity of the tumor suppressor p53, the main effector of cell cycle progression inhibition. The available data on the cross-talk between ribosome biogenesis and cell proliferation have been until now obtained in experimental model in which changes in ribosome biogenesis were obtained either by reducing the activity of the RNA polymerase I or by down-regulating the expression of the ribosomal proteins. The molecular pathways involved in the relationship between the effect of the inhibition of RNA polymerase III (Pol III) activity and cell cycle progression have been not yet investigated. In eukaryotes, RNA Polymerase III is responsible for transcription of factors involved both in ribosome assembly (5S rRNA) and rRNA processing (RNAse P and MRP).Thus, the aim of this study is characterize the effects of the down-regulation of RNA Polymerase III activity, or the specific depletion of 5S rRNA. The results that will be obtained might lead to a deeper understanding of the molecular pathway that controls the coordination between ribosome biogenesis and cell cycle, and might give useful information about the possibility to target RNA Polymerase III for cancer treatment.

Background: Circulating tumor cells (CTCs) and circulating free plasma DNA (FPDNA) have been proposed as biomarkers predictive of outcome and response to therapy in solid tumors. We investigated the multiple associations of the presence of CTC and the levels of FPDNA with the outcome and/or the response to chemotherapy in patients with localized breast cancer (LBC), metastatic breast cancer (MBC) and advanced ovarian cancer (AOC). Experimental Design: Blood samples were collected before (baseline), during and after therapy in 40 LBC and 50 AOC patients treated with neo-adjuvant chemotherapy. In 20 MBC patients blood was sampled at baseline and every each cycle of adjuvant chemotherapy. Real time PCR was applied to quantify FPDNA using the Quantifiler Human Quantification kit and CTCs through the detection of tumor-cell specific mRNA levels with or without epithelial enrichment. Results: At baseline CTCs were detected in 90% MBC, 42.5% LBC and 33% AOC patients respectively. The presence of baseline CTC was significantly associated with shorter overall survival (OS) in MBC and AOC patients, and shorter progression free survival (PFS) in LBC patients. Presence of CTCs at the end of neo-adjuvant chemotherapy was detected in 42% LBC and 18% AOC patients and was associated with shorter PFS and OS only in LBC. Increased FPDNA levels at baseline were found in 65% MBC, 17.5% LBC and 76% AOC patients but never related to OS. Baseline FPDNA high levels were associated with shorter PFS only in LBC patients. High FPDNA levels after neo-adjuvant chemotherapy were detected in 57% LBC and 48% AOC patients. Increased FPDNA after neo-adjuvant was associated with response to therapy and shorter PFS in AOC patients. Conclusions: Detection of CTCs may represent a prognostic and predictive biomarker in LBC, MBC and AOC. Quantification of FPDNA could be useful for monitoring response to therapy in AOC patients.