Disease fingerprinting with cDNA microarrays reveals distinct gene expression profiles in lethal type 1 and type 2 cytokine-mediated inflammatory reactions

Development of polarized immune responses controls resistance and susceptibility to many microorganisms. However, studies of several infectious, allergic, and autoimmune diseases have shown that chronic type-1 and type-2 cytokine responses can also cause significant morbidity and mortality if left unchecked. We used mouse cDNA microarrays to molecularly phenotype the gene expression patterns that characterize two disparate but equally lethal forms of liver pathology that develop in Schistosoma mansoni infected mice polarized for type-1 and type-2 cytokine responses. Hierarchical clustering analysis identified at least three groups of genes associated with a polarized type-2 response and two linked with an extreme type-1 cytokine phenotype. Predictions about liver fibrosis,  apoptosis, and granulocyte recruitment and activation generated by the microarray studies were confirmed later by traditional biological assays. The data show that cDNA microarrays are useful not only for determining  coordinated gene expression profiles but are also highly effective for molecularly “fingerprinting” diseased tissues. Moreover, they illustrate the potential of genome-wide approaches for generating comprehensive views on the molecular and biochemical mechanisms regulating infectious  disease pathogenesis.

Point Process Methodology for On-line Spatio-temporal Disease Surveillance

The AEGISS (Ascertainment and Enhancement of Gastrointestinal Infection Surveillance and Statistics) project aims to use spatio-temporal statistical methods to identify anomalies in the space-time distribution of non-specific, gastrointestinal infections in the UK, using the Southampton area in southern England as a test-case. In this paper, we use the AEGISS project to illustrate how spatio-temporal point process methodology can be used in the development of a rapid-response, spatial surveillance system. Current surveillance of gastroenteric disease in the UK relies on general practitioners reporting cases of suspected food-poisoning through a statutory notification scheme, voluntary laboratory reports of the isolation of gastrointestinal pathogens and standard reports of general outbreaks of infectious intestinal disease by public health and environmental health authorities. However, most statutory notifications are made only after a laboratory reports the isolation of a gastrointestinal pathogen. As a result, detection is delayed and the ability to react to an emerging outbreak is reduced. For more detailed discussion, see Diggle et al. (2003). A new and potentially valuable source of data on the incidence of non-specific gastro-enteric infections in the UK is NHS Direct, a 24-hour phone-in clinical advice service. NHS Direct data are less likely than reports by general practitioners to suffer from spatially and temporally localized inconsistencies in reporting rates. Also, reporting delays by patients are likely to be reduced, as no appointments are needed. Against this, NHS Direct data sacrifice specificity. Each call to NHS Direct is classified only according to the general pattern of reported symptoms (Cooper et al, 2003). The current paper focuses on the use of spatio-temporal statistical analysis for early detection of unexplained variation in the spatio-temporal incidence of non-specific gastroenteric symptoms, as reported to NHS Direct. Section 2 describes our statistical formulation of this problem, the nature of the available data and our approach to predictive inference. Section 3 describes the stochastic model. Section 4 gives the results of fitting the model to NHS Direct data. Section 5 shows how the model is used for spatio-temporal prediction. The paper concludes with a short discussion.

Évaluation du lavage articulaire avec des salines hypertoniques dans le traitement de l’arthrite septique chez le veau

L’arthrite septique chez les bovins est une affection le plus souvent d’origine bactérienne qui est une cause de boiterie fréquente associée à des pertes économiques importantes. Le traitement, qui doit être initié le plus rapidement possible, s’appuie sur l’utilisation combinée d’anti-inflammatoires non stéroïdiens, d’un ou de plusieurs lavages articulaires ainsi que d’antibiotiques administrés de façon systémique pour un minimum de 3 semaines. Cette durée d’administration constitue une difficulté pour les élevages dits biologiques pour lesquels un cahier des charges strict limite un recours prolongé aux antibiotiques. Ainsi le traitement efficace de diverses conditions infectieuses et celui de l’arthrite septique en particulier dans ces élevages peut être compromis. L’objectif de ce travail est de s’appuyer sur les propriétés antimicrobiennes des solutions de saline hypertonique (SSH) pour limiter l’utilisation des antibiotiques dans les cas d’arthrite septique chez les veaux en intégrant ces solutions pour le lavage des articulations infectées. Notre première étude a consisté à déterminer la sécurité d’emploi de deux concentrations de SSH (une commerciale à 7.2% et une maison à 15%) dans des articulations supposées saines chez le veau. Une synovite sévère associée à des signes cliniques caractéristiques d’atteintes articulaires a été observé lors de l’utilisation de SSH 15%. Son utilisation clinique comme solution de lavage articulaire est par conséquent déconseillée. Concernant la SSH 7.2%, malgré une synovite d’intensité variable, nous n’avons pas noté des signes cliniques caractéristiques d’atteintes articulaires. Son utilisation dans un contexte expérimental d’infection articulaire nous a paru réaliste. Notre seconde étude a permis d’évaluer les effets du lavage articulaire avec de la SSH 7.2% dans un modèle expérimental d’infection à Escherichia coli. Trois groupes de traitement ont été constitués. Dans le premier groupe (traitement standard), un lavage était effectué avec du lactate de Ringer (LRS) et les veaux recevaient une administration biquotidienne de ceftiofur par voie intraveineuse pour 21 jours. Dans le deuxième groupe (LRS), un lavage était effectué avec du LRS et aucun antibiotique n’était administré. Enfin dans le troisième groupe (SSH), un lavage était effectué avec de la SSH 7.2% sans qu’aucun antibiotique ne soit administré. Tous les veaux ont reçu du kétoprofen quotidiennement pendant 3 jours. L’inoculation s’est fait au jour 1 et les traitements ont débuté au jour 2. L’efficacité des traitements a été établie sur des critères cliniques, bactériologiques et cytologiques. Dans le modèle que nous avons utilisé, les trois groupes de traitements ont conduits à une guérison clinique et bactériologique satisfaisante (absence de boiterie, de douleur et de croissance bactérienne dans le liquide articulaire en fin d’étude). La guérison cytologique n’a quant à elle pas été jugée satisfaisante avec des moyennes de comptage et de pourcentage en neutrophiles tout groupe confondu bien supérieures aux valeurs normales (11.39x109/l de neutrophiles représentant 74.73% des leucocytes en fin d’étude). Le traitement avec la SSH 7.2% s’est révélé être significativement plus traumatique et pas plus efficace dans l’élimination de l’infection comparativement au traitement LRS. D’autre part, le lavage articulaire au LRS s’est révélé être aussi efficace et sécuritaire que le traitement standard de l’arthrite septique qui incluait 21 jours de ceftiofur administré par voie intraveineuse. Ainsi, bien que le lavage avec de la SSH 7.2% n’est pas démontré de résultats satisfaisants qui permettrait de limiter le recours aux antibiotiques dans les filières biologiques, l’association d’un lavage au LRS avec le ketoprofen s’est révélée être une alternative possible. De nouvelles études sont requises pour confirmer ses résultats et pour déterminer le rôle respectif du lavage articulaire et du ketoprofen dans la guérison lors d’arthrite septique.

Atividade antimalárica de plantas medicinais da biorregião do Araripe-CE em modelo murino - Plasmodium berghei

Malaria, also popularly known as maleita , intermittent fever, paludism, impaludism, third fever or fourth fever, is an acute infectious febrile disease, which, in human beings, is caused by four species: Plasmodium falciparum, P. vivax, P. malariae and P. ovale. Malaria, one of the main infectious diseases in the world, is the most important parasitoses, with 250 million annual cases and more than 1 million deaths per year, mainly in children younger than live years of age. The prophylactic and therapeutic arsenal against malaria is quite restricted, since all the antimalarials currently in use have some limitation. Many plant species belonging to several families have been tested in vivo, using the murine experimental model Plasmodium berghei or in vitro against P. falciparum, and this search has been directed toward plants with antithermal, antimalarial or antiinflammatory properties used in popular Brazilian bolk medicine. Studies assessing the biological activity of medicinal plant essential oils have revealed activities of interest, such as insecticidal, spasmolytic and antiplasmodic action. It has also been scientifically established that around 60% of essential oils have antifungal properties and that 35% exhibit antibacterial properties. In our investigation, essential oils were obtained from the species Vanillosmopsis arborea, Lippia sidoides and Croton zethneri which are found in the bioregion of Araripe-Ceará. The chemical composition of these essential oils was partially characterized and the presence of monoterpenes and sesquiterpenes. The acute toxicity of these oils was assessed in healthy mice at different doses applied on a single day and on four consecutive days, and in vitro cytotoxicity in HeLa and Raw cell lines was determined at different concentrations. The in vivo tests obtained lethal dose values of 7,1 mg/Kg (doses administered on a single day) and 1,8 mg/Kg (doses administered over four days) for 50% of the animals. In the in vitro tests, the inhibitory concentration for 50% of cell growth in Hela cell lines was 588 μg/mL (essential oil from C. zethneri after 48 h), from 340-555 μg/mL (essential oil from L. sidoides, after 24 and 48 h). The essential oil from V. arborea showed no cytotoxicity and none of the essential oils were cytotoxic in Raw cell lines. These data suggest a moderate toxicity in the essential XVIII oils under study, a finding that does not impede their testing in in vivo antimalarial assays. Was shown the antimalarial activity of the essential oils in mice infected with P. berghei was assessed. The three species showed antimalarial activity from 36%-57% for the essential oil from the stem of V. arborea; from 32%-82% for the essential oil from the leaves of L. sidoides and from 40%-70% of reduction for the essential oil from the leaves of C. zethneri. This is the first study showing evidence of antimalarial activity with these species from northeast Brazil. Further studies to isolate the active ingredients of these oils are needed to determine if a single active ingredient accounts for the antimalarial activity or if a complex integration of all the compounds present occurs, a situation reflected in their biological activity

Da negatividade a positividade: possível trânsito de saberes, práticas e representações sociais sobre o estigma da hanseníase

Leprosy is a chronic infectious-contagious disease, caused by Mycobacterium leprae, manifested by dermatological and neurological signs and symptoms and has great disabling power. It was marked by a strong stigma throughout its history, since its bearers represented a threat, target of fear and social contempt. Currently, leprosy has treatment and cure, and the need to separate the diseased from family and social environment is no more necessary. However, patients still suffer prejudice and discrimination. This study aimed to understand the social representations of leprosy that interfere modifying mental health of the patient with leprosy in relation to stigma and prejudice. This is a descriptive and exploratory study, with qualitative approach, which involved 22 users of the Special Care Clinic in Infectious Diseases at the Hospital Giselda Trigueiro, located in Natal / RN. They were in use of multidrug therapy in the period of data collection, were of both sexes, aged between 16 and 80 years of age and classified as paucibacillary or multibacillary. The study was approved by the UFRN Ethics in Research Committee. Data collection was performed by filling the questionnaire identification and then for conducting the semi-structured interview, which was recorded. After the end of data collection, there was the construction of tables and graphs, using the Microsoft Excel Start 2010 for proper characterization of the research subjects; and for the treatment of the data obtained from the interviews, was used the Content Analysis and based on the Theory of Social Representations. The subjects studied were mostly male (64%), married or in a stable relationship (68%), concentrated in the age group 50-60 years (36%) and 28-38 years (23%), had at most elementary education (65%) and were low-income (59%). Of the total respondents, 64% were classified as multibacillary, with predominantly dimorfous form, and 50% had disability grade I or II, with different periods of diagnosis. The reports originate two categories: 1. The negative meanings of illness and leprosy; and 2. The positive meanings of illness in leprosy, which were subsequently subdivided into subcategories. Thus, it was found that in the group studied, the social representation of leprosy experiences a moment of transition, as regards the understanding of the disease and its way of experiencing the disease process. Such representation is anchored in the quality of information on the disease of its bearers and aimed at an attempt to face the illness of leprosy as a "normal process". It was found in this study that the transition is due to the work of combating stigma and consequences of leprosy, which is able to gradually transform reality, both regarding the team work of reference, and in relation to a broader character, of actions of health education, which favors overcoming of psychosocial disabilities

Estimação de parâmetros genéticos para resistência à infecção por IMNV em camarões Litopenaeus vannamei por meio de análise de sobrevivência

The main specie of marine shrimp raised at Brazil and in the world is Litopenaeus vannamei, which had arrived in Brazil in the `80s. However, the entry of infectious myonecrosis virus (IMNV), causing the infectious myonecrosis disease in marine shrimps, brought economic losses to the national shrimp farming, with up to 70% of mortality in the shrimp production. In this way, the objective was to evaluate the survival of shrimps Litopenaeus vannamei infected with IMNV using the non parametric estimator of Kaplan-Meier and a model of frailty for grouped data. It were conducted three tests of viral challenges lasting 20 days each, at different periods of the year, keeping the parameters of pH, temperature, oxygen and ammonia monitored daily. It was evaluated 60 full-sib families of L. vannamei infected by IMNV in each viral challenge. The confirmation of the infection by IMNV was performed using the technique of PCR in real time through Sybr Green dye. Using the Kaplan-Meier estimator it was possible to detect significant differences (p <0.0001) between the survival curves of families and tanks and also in the joint analysis between viral challenges. It were estimated in each challenge, genetic parameters such as genetic value of family, it`s respective rate risk (frailty), and heritability in the logarithmic scale through the frailty model for grouped data. The heritability estimates were respectively 0.59; 0.36; and 0.59 in the viral challenges 1; 2; and 3, and it was also possible to identify families that have lower and higher rates of risk for the disease. These results can be used for selecting families more resistant to the IMNV infection and to include characteristic of disease resistance in L. vannamei into the genetic improvement programs

Papilomatose oral em cães: revisão da literatura e estudo de doze casos

Canine papillomatosis is an infectious viral disease characterized by oral, cutaneous or ocular papillomas, usually benign. The treatment is indicated in animals, with multiple tumors that produce pharyngeal obstruction, and problems, of eating or for aesthetic reasons. Different treatment protocols have been proposed, including surgical excision, cryosurgery, electro surgery, autogenous or recombinant vaccines, imunomodulators drugs, systemic and intralesional chemotherapy. In this study were reviewed the more important aspects of canine oral papillomatosis. In the 12 studied animals, the papillomas were observed predominantly in mouth, gum and palate regions, in puppies until 12 months, presenting combined infection with ehrlichiosis. The treatment using Propionibacterium acnes and/or autogenous vaccine showed efficacy in eight dogs (66.7%).

Síndromes oculares secundárias a infecção pelo Herpesvirus felino-1-Revisão

The feline infectious respiratory disease is the most common diagnosed infection in the veterinary clinic routine, being the Feline Herpesvirus1 the most important causal agent. Once infected, the cat will become a lifetime latent carrier, experiencing episodes of viral reactivation and spontaneous spread especially when there is a stress factor involved. This virus acts in the upper respiratory system and is also associated with eye diseases. The diagnosis is made by viral isolation and treatment protocol is based on a topic antiviral therapy, even though many of them are epiteliotoxic and may progress with intense discomfort in felines.The purpose of this paper is to describe the main ocular manifestations and syndromes seen in cats suffering from feline herpesvirus. Conjunctivitis, epithelial and stromal keratitis, corneal ulceration and indolent ulcers are the main ocular manifestations associated with viral infection, whereas symblepharon, keratoconjunctivitis sicca, proliferative keratitis and corneal sequestration are the main eye syndromes that can be observed in infected animals.

Perfil sérico de estresse oxidativo, antioxidantes e micronutrientes em pacientes com hanseníase

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Efeito de desnutrição e das citocinas pró-inflamatórias na infecção experimental em camundongos Balb/c infectados com Trypanosoma cruzi

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Soroepidemiologia da sífilis em gestantes e seus recém-nascidos

A sífilis é uma doença infecto-contagiosa sistêmica causada pelo Treponema pallidum, parasita exclusivo do homem, cuja transmissão se faz essencialmente pelo contato sexual. A incidência desífilis congênita tem atingido proporções de verdadeira epidemia, apesar do conhecimento de medidas que poderiam controlar esta doença. A investigação caracterizou gestantes com sífilis internadas na FSCMPA no período de janeiro de 2001 até junho de 2003, quanto às características sócio-demográficas, comportamento para promoção da saúde sexual e reprodutiva, dados sorológicos e clínicos relacionados à sífilis no binômio mãe/recém-nascido. O estudo é de natureza analítico-descritivo, de corte transversal, com 245 gestantes, a partir da revisão de prontuários destes pacientes, com sorologia positiva para sífilis e do recém-nascido, testados pelo método de VDRL. A incidência de sífilis em gestantes foi de 1,73% do total de pacientes internadas nos últimos 2 anos e meio. O perfil epidemiológico demonstrou que os principais fatores de risco para aquisição da sífilis na gestação foram: ausência de acompanhamento pré-natal e de tratamento, inclusive do parceiro sexual. De acordo com a soropositividade materna no pós-natal, verificou-se que a possibilidade de um recém-nascido ter sífilis, se VDRL positivo, foi de 98,68%. A icterícia e o baixo peso foram os sinais clinícos de maior ocorrência, a prematuridade também foi sinal clínico observado. Estas análises revelam a necessidade de campanhas educativas mais abrangentes, sobre os fatores de risco para aquisição desta enfermidade e um melhor atendimento às gestantes no pré-natal, com acompanhamento e diagnóstico controle das gestantes.

O comportameno clínico-cardiológico, eletrocardiográfico e radiológico do tórax de pacientes com leptospirose internados no Hospital Universitário João de Barros Barreto, no período de 2002-2003, Belém-Pará

A leptospirose apresenta alta prevalência em nossa região. É uma doença infecciosa, multissistêmica, que acomete vários órgãos e o envolvimento cardíaco é freqüente, constituindo atualmente uma das principais causas de morte dos portadores desta afecção. O objetivo do trabalho foi avaliar o comportamento clínico-epidemiológico, eletrocardiográfico e radiológico do tórax de pacientes com diagnóstico clínico-epidemiológico, eletrocardiográfico e radiológico do tórax de pacientes em diagnóstico clínico-epidemiológico de leptospirose na fase aguda e em ambiente hospitalar. Para este propósito, foi realizado um estudo transversal com 41 pacientes, seis do sexo feminino e 35 do sexo masculino, com idades entre 15 e 78 anos, internados no Hospital Universitário João de Barros Barreto, no período de fevereiro de 2002 a junho de 2003. Os participantes do estudo submeteram-se à anamnese e exame clínico, com ênfase ao aparelho cardiovascular, realizaram de um a três eletrocardiogramas, uma radiografia do tórax e exames laboratoriais de rotina. Analisando-se os achados clínicos, 37 (90,2 %) apresentaram sinais e sintomas compatíveis com envolvimento miocárdico. As anormalidades eletrocardiográficas ocorreram em 20 casos, correspondendo a 48,7 % do total. O nível médio de potássio foi de 3,8 meq/l. A maioria das alterações foram reversíveis e, a principal, correspondeu ao supradesnivelamento de segmento ST, sem diferença estatística significante (p>0,05) entre elas. Nos 37 enfermos que apresentaram sintomas e sinais sugestivos de comprometimento cardíaco, não houve diferença estatística significativa (p> 0,05) entre os eletrocardiogramas normais e os alterados. Em apenas oito indivíduos houve anormalidades radiológicas (19,5 %), sendo que o aumento discreto do ventrículo esquerdo com infiltrado intersticial nas bases pulmonares foi o principal achado, com diferença estatística significante (p<0,05) entre outros tipos de infiltrados pulmonares. Portanto, neste estudo, os principais achados clínicos foram: hepatomegalia e dispnéia; eletrocardiográficos: supradesnível de segmento ST e taquicardia sinusal com reversão na maioria dos caos e radiológicos: aumento ventricular esquerdo discreto com infiltrado pulmonar nas bases.

Caracterização morfológica e fenotípica de leveduras do gênero Cryptococcus com ênfase na pesquisa de Cryptococcus neoormans isoladas de amostras de água de mar e areia de três ambientes costeiros do estado de São Paulo: Canal de São Sebastião, Baixada Santista e Ubatuba

The yeast Cryptococcus neoformans is the etiologic agent of cryptococcosis, an infectious cosmopolitan disease that affects humans. Although rare, this disease is potentially fatal, especially for immunocompromised hosts. This pathogen is frequently isolated from excrements of pigeons and parrots, with many environmental sources such as birds, pigeon droppings, eucalyptus leaves, decaying trees, towers, churches and places of storage of grain (the port area). The isolation of this microorganism has been obtained also from the aquatic environment. The identification of environmental sources is needed to protect human health, especially susceptible populations such as immunocompromised. Therefore, this study investigated the presence of Cryptococcus neoformans in yeast isolates obtained from samples of sea water and sand from three regions of São Paulo: São Sebastião Channel, Santos and Ubatuba. Isolates were analyzed according to micro-and macroscopic characteristics and biochemical tests: microculture, urease, ink nankin, auxanograma, zymogram and phenol. We analyzed 199 isolates, 175 of which had features suggestive for Cryptococcus spp. in microculture. All these 175 isolates were sown in the Christensen urea middle to verify the production of urease and submitted to the technique nankin ink to visualize the capsule. Of these, only 24 were selected for the next test that was the auxanograma (assimilation of carbohydrate and nitrogen). Of the 24, 10 were tested in zymograms (fermented sugar), from which 5 were selected for the phenoloxidase test in medium containing dopamine. None of the 5 isolates tested had black or brown color characteristic of Cryptococcus neoformans. According to these tests, we arrived at 5 isolates identified to the genus Cryptococcus, but not the neoformans specie

Comparação entre métodos diagnósticos da tuberculose em bovinos abatidos em matadouros-frigoríficos do Estado de São Paulo

Pós-graduação em Medicina Veterinária - FCAV

Nanoencapsulação de compostos de rutênio, análise de sua atividade anti - Mycobacterium tuberculosis e biodisponibilidade oral

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)