SummarySplenectomy results in an increased risk of sepsis. The autogenous transplant of the spleen is an option for preserving splenic functions after total splenectomy. In this study, the capacity of animals undergoing autogenous spleen transplantation to respond to Staphylococcus aureus infection was investigated. BALB/c mice were divided into three groups: splenectomy followed by autotransplantation in the retroperitonium (AT), splenectomized only (SP) and operated non-splenectomized sham control (CT). Thirty days after surgery the mice were infected intravenously with S. aureus. Splenectomized mice had a higher number of colony-forming units (CFU) of S. aureus in liver and lungs in comparison with either AT or with CT mice (P < 0·05). Higher CFU numbers in lung of SP mice correlated with elevated production of interleukin-10 associated with a lower production of interferon-g and tumour necrosis factor-a. However, systemically, the level of tumour necrosis factor-a was higher in the SP group than in CT or AT. Lower titres of specific anti-S. aureus immunoglobulin (Ig)M and IgG1 were observed 6 days after infection in SP mice in comparison either with the AT or CT groups. Thus, splenectomy is detrimental to the immune response of BALB/c mice against infection by S. aureus which can be re-established by autogenous implantation of the spleen.
Apoptosis of macrophages during pulmonary Mycobacterium bovis infection: correlation with intracellular bacillary load and cytokine levels Introduction Tuberculosis (TB) is a disease of importance worldwide responsible for two million deaths and eight million new cases annually.1,2 The causative agents of TB belong to the Mycobacterium tuberculosis complex, which is a group of closely related mycobacteria including M. tuberculosis and Mycobacterium bovis. The tubercle bacilli enter the organism principally through the respiratory tract and phagocytosis of the bacilli by alveolar macrophages is the first event in the host-pathogen interaction.3,4 These bacteria are able to avoid phagosome maturation and fusion with lysosomes and so escape from the major cytotoxic mechanisms of phagocytes. 5,6 Surviving in the interior of the phagosome of the macrophage, the bacillus is guaranteed an environment that protects it from the effector mechanisms of the host and allows it to replicate. 7 During the initial stages of infection, control of proliferation of intracellular bacteria depends on natural resistance mediated by macrophages. 8,9 Besides the innate effector mechanisms used by these cells, it has been suggested that apoptosis of the infected macrophages constitutes an alternative strategy that can contribute in several ways to the host defence. This type of cellular death deprives the pathogen of its intracellular refuge, and obstructs its propagation by sequestering and retaining the mycobacteria within apoptotic bodies, which ultimately are engulfed by recruited phagocytes. [10][11][12][13][14] Recent studies have demonstrated that virulent strains of mycobacteria, such as M. tuberculosis H37Rv and M. bovis wild-type, induce significantly less apoptosis of the infected macrophages than the attenuated strains M. tuberculois H37Ra and M. bovis bacillus CalmetteGuérin (BCG), indicating that inhibition of apoptosis of
BACKGROUND: Helicobacter pylori infection is the most important risk factor for gastric atrophy and intestinal metaplasia, both considered gastric cancer precursor lesions. Therefore, the investigation of the occurrence of H. pylori infection, precursor lesions and associated factors guides the adoption of specific strategies for the control this type of cancer. OBJECTIVE: To evaluate the prevalence of H. pylori infection in patients undergoing upper digestive endoscopy, as well as the prevalence of intestinal metaplasia, atrophy and chronic inflammation and their association with H. pylori infection. METHODS: A retrospective study was performed based on reports of gastric endoscopic biopsies performed in a private laboratory affiliated to the Brazilian Public Health System (SUS). Patients were evaluated for age, gender and type of health service. The samples were evaluated for the presence of H. pylori, and also of chronic inflammation, intestinal metaplasia and glandular atrophy. RESULTS: Of a total of 4,604 patients (mean age 51±16.6), 63.9% were female and 63.1% coming from private health care service. The prevalence of H. pylori infection was 31.7% (n=1,459), and the percentage of infection was significantly higher in patients from public health service (42.0%) in relation to patients from private health service (25.6%). Among H. pylori (+) patients, a higher percentage of intestinal metaplasia (17.7% vs 13.3%) and glandular atrophy (17.6% vs 6.9%) were observed when compared to those H. pylori (-) (P<0.01). From the patients H. pylori (+) with at least one type of precursor lesion (n=418), 161 (38.5%) had metaplasia and chronic inflammation, 160 (38.3%) had atrophy and chronic inflammation and finally 97 (23.2%) presented metaplasia, atrophy and chronic inflammation simultaneously. CONCLUSION: The present study reinforces the association of H. pylori infection with gastric cancer precursor lesions in a Brazilian population, emphasizing the importance of infection prevention measures, as well as the treatment of infected patients, especially in regions with lower socioeconomic levels that show a higher prevalence of infection by H. pylori.
Trends in Psychiatry and Psychotherapy Review ArticleResumo Introdução: O objetivo deste estudo foi fazer uma revisão da literatura abrangendo o uso das diferentes abordagens da terapia baseada em mindfulness no tratamento dos transtornos de humor e ansiedade, incluindo suas habilidades e sua relação com a regulação emocional e com o medo da avaliação negativa. Métodos: Uma revisão de literatura foi realizada através de busca pelas bases científicas PubMed e PsycINFO, com as seguintes palavras-chave: mindfulness, transtornos do humor e transtornos de ansiedade. A pesquisa abrangeu os últimos 10 anos. A busca resultou em 532 artigos, sendo 24 selecionados e 16 incluídos nesta revisão. Resultados: Foram revisados seis artigos sobre programa de redução de estresse baseado em mindfulness, quatro artigos sobre terapia cognitiva baseada em mindfulness, e três sobre medo da avaliação negativa e regulação emocional. Todos os artigos abordaram mindfulness com relação aos transtornos de humor e ansiedade Conclusão: A literatura nessa área sugere que mindfulness é uma estratégia eficaz no tratamento dos transtornos de humor e ansiedade e é eficaz no protocolo de terapia em diferentes formatos, incluindo virtual. O uso de mindfulness continua a se expandir nos modelos científicos. Descritores: Mindfulness, transtornos do humor e transtornos ansiosos. AbstractIntroduction: The objective of this study was to conduct a review of the literature covering the use of different mindfulnessbased therapy approaches in treatment of mood and anxiety disorders, including mindfulness skills and mindfulness linked to emotional regulation and fear of negative appraisal. Methods: A review was conducted of literature identified by searching the scientific databases PubMed and PsycINFO with the following keywords: mindfulness, mood disorders, and anxiety disorders. The search covered the past 10 years. The search returned 532 articles, 24 were selected, their full texts were read, and 16 were included in this review. Results: Six articles about mindfulness-based stress reduction, four about mindfulness-based cognitive therapy, and three about fear of negative appraisal and emotional regulation were reviewed. All of the articles covered mindfulness in relation to mood and anxiety disorders. Conclusions: The literature in this field suggests that mindfulness is an effective strategy for the treatment of mood and anxiety disorders and is effective in therapy protocols with different structures including virtual modalities. Use of mindfulness in scientific models continues to expand.
SummaryApoptosis of macrophages has been reported as an effective host strategy to control the growth of intracellular pathogens, including pathogenic mycobacteria. Tumour necrosis factor-a (TNF-a) plays an important role in the modulation of apoptosis of infected macrophages. It exerts its biological activities via two distinct cell surface receptors, TNFR1 and TNFR2, whose extracellular domain can be released by proteolysis forming soluble TNF receptors (sTNFR1 and sTNFR2). The signalling through TNFR1 initiates the majority of the biological functions of TNF-a, leading to either cell death or survival whereas TNFR2 mediates primarily survival signals. Here, the expression of TNF-a receptors and the apoptosis of alveolar macrophages were investigated during the early phase of infection with attenuated and virulent mycobacteria in mice. A significant increase of apoptosis and high expression of TNFR1 were observed in alveolar macrophages at 3 and 7 days after infection with attenuated Mycobacterium bovis but only on day 7 in infection with the virulent M. bovis. Low surface expression of TNFR1 and increased levels of sTNFR1 on day 3 after infection by the virulent strain were associated with reduced rates of apoptotic macrophages. In addition, a significant reduction in apoptosis of alveolar macrophages was observed in TNFR1 À/À mice at day 3 after bacillus Calmette-Gu erin infection. These results suggest a potential role for TNFR1 in mycobacteria-induced alveolar macrophage apoptosis in vivo. In this scenario, shedding of TNFR1 seems to contribute to the modulation of macrophage apoptosis in a strain-dependent manner.
Bovine tuberculosis is a major cause of economic loss in countries where it is endemic, and in some countries, it may be a significant zoonotic disease problem. Therefore, new strategies for vaccine development are required, and among them, genetic immunization has potential value. The main goal of this study was to test the Mycobacterium bovis Ag85B gene as a DNA vaccine following challenge with an M. bovis virulent strain (ATCC 19274). Groups of BALB/c mice (n ؍ 10) were immunized four times intramuscularly with the pCI-Ag85B construct or the pCI vector alone as the control. High titers of total immunoglobulin G (IgG), IgG1, and IgG2a anti-Ag85B were measured in pCI-Ag85B immunized mice when compared to the pCI control group. Regarding cellular immunity, significant levels of gamma interferon (IFN-␥) (1,100 ؎ 157 pg/ml) and tumor necrosis factor alpha (650 ؎ 42 pg/ml) but not interleukin-4 were detected in splenocyte culture supernatants of pCI-Ag85B-vaccinated mice following stimulation with recombinant Ag85B. Further, the main source of IFN-␥ is CD8؉ T cells, as demonstrated by intracellular cytokine staining. As far as protection, a significant reduction in bacterial load in spleens (P < 0.05) was detected in pCI-Ag85B-immunized mice compared to the pCI vector control group. The results obtained here suggest that use of the Ag85B DNA vaccine is a promising strategy to control M. bovis infection due to its ability to induce a Th1 type of immune response. However, protective efficacy needs to be improved, since partial protection was achieved in spleens but not in lungs of vaccinated mice.
Resumo: FUNDAMENTOS: O câncer de pele é o mais frequente tipo de câncer humano e mostra aumento de sua incidência. Em muitos casos, antes do surgimento do carcinoma, instala-se uma lesão precursora, ceratose actínica, podendo evoluir para carcinoma espinocelular. Estudos buscam determinar os parâmetros com significado prognóstico na predição daqueles tumores que terão comportamento mais agressivo. OBJETIVO: Avaliar a expressão dos marcadores de proliferação celular (PCNA, Ki-67) e apoptose (p53, Bcl-2), em portadores de carcinoma espinocelular e ceratose actínica. MÉTODO: Foram estudadas amostras de 30 pacientes: sendo dez portadores do carcinoma espinocelular; dez de ceratose actínica e dez indivíduos livres de lesões submetidos à blefaroplastia. RESULTADOS: A proteína p53 foi expressa em todos os casos estudados, embora apresentassem padrões quantitativos diferentes. O Bcl-2 foi expresso em baixa intensidade. Em seis casos de ceratose actínica, nas peles de blefaroplastia, e negativo nos casos de carcinoma espinocelular. O PCNA exibiu expressão intensa, em todas as amostras. O Ki-67 apresentou expressão variável, nos casos de carcinoma e de ceratose, e negativo na pele de pálpebra. CONCLUSÃO: A expressão do Ki-67 e a não-expressão de Bcl-2, no grupo CEC, indica intensificação da atividade proliferativa. Ao passo que, a maior expressão de p53 e Bcl-2, no grupo CA, sugere imortalização celular. Palavras-chave: Apoptose; Carcinoma de células escamosas; Ceratose; Imuno-histoquímica; Proliferação de células Abstract: BACKGROUND: Skin cancer is the most frequent type of human cancer and has shown an increase in its incidence. In many cases, before the onset of the carcinoma, there might be a precursor lesion -actinic keratosis, which can develop into squamous cell carcinoma. Studies have been carried out in order to determine the parameters that have prognostic significance in predicting those tumors which have more aggressive behavior. OBJECTIVE: To evaluate the expression of markers of cell proliferation (PCNA, Ki-67) and apoptosis (p53,Bcl-2) in patients with squamous cell carcinoma and actinic keratosis. METHOD: We studied samples from 30 patients, ten patients of squamous cell carcinoma, ten with actinic keratosis and ten lesion-free samples from blepharoplasty. RESULTS: p53 protein was expressed in all cases with different quantitative patterns. Bcl-2 was expressed at low intensity in six cases of actinic keratosis in the skin from blepharoplasty and negative in cases of squamous cell carcinoma. PCNA showed intense expression in all samples. Ki-67 showed variable expression in cases of keratosis and carcinoma and negative in the skin from the eyelid. CONCLUSION: The high expression of Ki-67 associated with low expression of Bcl-2 indicates proliferation in the carcinoma group. Thus, expression of p53 and Bcl-2 in patients with actinic keratosis indicates cell immortalization.
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