Autophagy in Preeclampsia

Autophagy may be involved in gestation complicated by preeclampsia (PE) due to the presence of placental lesions caused by hypoxia at fetomaternal interphase. Autophagy is a lysosomal degradation pathway, removing protein aggregates and organelles damaged and thereby maintaining cell integrity. In preeclampsia, deficient myometrial penetration by extravillous cytotrophoblast occurs during the first trimester of pregnancy, leading to placental insufficiency. Several placental functions, like nutrient and oxygen input to the fetus during pregnancy, might benefit or even rely on autophagy and related material recycling within the cell. Deficiency in autophagy mechanism has been correlated to inflammatory responses. Autophagy is regulated during placentation and appears to be a possible factor in the development of preeclampsia. In this chapter, we intend to discuss evidence on autophagy pathway in pregnancy and the crosstalk between autophagy and inflammation in preeclampsia

Efeito inibidor da deferoxamina sobre a sobrevivência do Paracoccidioides brasiliensis em monócitos humanos: reversão por holotransferrina e não por apotransferrina

The mechanisms used by Paracoccidioides brasiliensis to survive into phagocytic cells are not clear. Cellular iron metabolism is of critical importance to the growth of several intracellular pathogens whose capacity to multiply in mononuclear phagocytes is dependent on the availability of intracellular iron. Thus, the objective of this paper was to investigate the role of intracellular iron in regulating the capacity of P. brasiliensis yeast cells to survive within human monocytes. Treatment of monocytes with deferoxamine, an iron chelator, suppressed the survival of yeasts in a concentration-dependent manner. The effect of deferoxamine was reversed by iron-saturated transferrin (holotransferrin) but not by nonsaturated transferrin (apotransferrin). These results strongly suggest that P. brasiliensis survival in human monocytes is iron dependent.Os mecanismos utilizados pelo Paracoccidioides brasiliensis para sobreviver em células fagocitárias ainda não estão elucidados. O metabolismo celular férrico é muito importante para o crescimento de inúmeros patógenos intracelulares cuja capacidade de se multiplicarem em fagócitos mononucleares é dependente da disponibilidade intracelular do íon ferro. Assim, o objetivo deste trabalho foi investigar o papel do ferro intracelular sobre a capacidade do P. brasiliensis sobreviver em monócitos humanos. O tratamento de monócitos com deferoxamina, uma droga quelante, diminuiu a sobrevivência de leveduras do fungo de forma dose-dependente. O efeito inibidor da deferoxamina sobre a sobrevivência do P. brasiliensis foi revertido por transferrina saturada com ferro (holotransferrina) mas não por transferrina insaturada (apotransferrina). Estes resultados sugerem que a sobrevivência do P. brasiliensis em monócitos humanos é dependente do íon ferro

Cervical, intradermal reaction for diagnosis of Eurytrema sp infection in cattle

Foram realizadas intradermo-reações (IDR) cervicais em 101 bovinos, machos e fêmeas, que receberam, simultaneamente e ao acaso, em sete áreas adjacentes, 0,1 ml de salina e igual volume de um extrato antigênico de Eurytrema sp, nas seguintes concentrações de proteína: 25ng/ml, 50|jg/ml, 100pg/ml, 250pg/ml, 500[jg/ml e 1 mg/ml. Feitas todas as injeções intradérmicas e, ao final de 30min, com auxílio de uma régua milimetrada, de cada pápula produzida foram medidos os dois diâmetros maiores, extraídas as médias (diâmetros inicial, D,e final, D) e calculada a diferença Di - D,. No dia seguinte acompanhava-se o abate de cada animal a fim de se verificar, por meio de exames macroscópicos dos respectivos pâncreas, se eram ou não parasitados por Eurytrema sp. Concluiu-se, então, que o extrato salino bruto do trematódeo, utilizado como antígeno, deverá conter, no momento de sua utilização, concentração de proteínas equivalente a 250pg/ml e, respectivamente, serem consideradas positivas e negativas as IDR que apresentarem Di - D, > 2,5mm e Di - D* < 2,5mm.Cervical, intradermal reactions (IDR) were performed in 101, male and female, adult cattle slaughtered in the Viçosa abattoir Each animal received simultaneously and randomly 0,1ml of salina and salina extract of Eurytrema sp antigen in the following protein concentrations: 25(jg/ml, 50|jg/ml, 100pg/ml, 250Mg/ml, 500pg/ml and 1 mg/ml. Immediately after the injections, as well as 30 minutes later, the millimetered whealswere measured by means of a millimetered ruler in order to get the mean diameter in both times (D, initial mean diameter; Di, final mean diameter). Then, Di - D, was calculated, and in the next day each pancreas was macroscopically examined in order to investigate the parasitic condition. The following conclusions were reached: 1) all IDR showing wheal increase of 2.5mm might be considered positive, whereas the other ones (with Di - D, < 2.5mm) might be regarded as negative; 2) Eurytrema sp antigen, at the moment of its use, ought to have a concentration of 250|jg/ml of protein/ml

Paracoccidioidioidomicose experimental do hamster: estudo da imunidade celular e humoral, correlação com a morfologia das lesões de inoculação e disseminação

BV UNIFESP: Teses e dissertaçõe

Transferência de resposta imune ao Paracoccidioides brasiliensis em hamsters, com fator de transferência dialisável: estudo da especificidade e dos efeitos sobre a infecção experimental

BV UNIFESP: Teses e dissertaçõe

Immunologic aspects of West syndrome and evidence of plasma inhibitory effects on T cell function

OBJETIVO: O objetivo deste estudo foi determinar o perfil da deficiência imune em um grupo bem definido de epilepsia: crianças com síndrome de West (SW) e seus padrões EEG de evolução, idade-dependentes, como os complexos onda-aguda- onda lenta generalizadas da síndrome de Lenox-Gastaut (SLG) e as pontas multifocais independentes (PMI). MÉTODO: Um grupo de 50 crianças, 33 com SW, 10 com SLG, 7 com PMI e 20 crianças sadias (controle) foram avaliadas em relação aos seguintes parâmetros:determinação de subpopulações de linfócitos T (CD1, CD3, CD4 e CD8), relação CD4/CD8 e resposta proliferativa de linfócitos frente a fitohemaglutinina (PHA), na presença de plasma autólogo ou de plasma AB (homólogo). A prova cutânea de sensibilização ao Dinitroclorobenzeno (DNCB) foi realizada apenas nos pacientes. Os níveis séricos de IgG, IgA e IgM foram comparados aos valores normais em crianças Brasileiras, em diferentes faixas etárias. RESULTADOS: A resposta ao DNCB foi ausente ou fracamente reativa em 76% dos pacientes. Níveis séricos elevados de IgG (45,7%) e de IgM (61,4%) e baixos de IgA (23,9%) foram detectados nos pacientes. A determinação das subpopulações de linfócitos T em sangue periférico mostrou: deficiência nas proporções de células CD3+ (p<0,05) e de CD4+ (p<0,05), aumento de CD8+ (p<0,01) e diminuição da relação CD4 / CD8 (p<0,001). A proporção de células CD1+ no grupo controle manteve-se menor que 3%, enquanto que em 18% dos pacientes esses níveis variaram entre 3 e 11%. A resposta proliferativa de linfócitos frente a PHA revelou índices blastogênicos significativamente mais baixos apenas quando células dos pacientes foram cultivadas na presença do próprio plasma (plasma autólogo). Quando estas células foram cultivadas na presença de plasma AB, não se evidenciou diferença significativa em relação ao grupo controle. CONCLUSÃO: A imunodeficiência na SW caracterizou-se por: anergia, alteração de imunidade mediada por células e dos níveis de imunoglobulinas, presença de timócitos imaturos na circulação periférica e deficiência funcional de linfócitos T induzida por fatores plasmáticos inibidores. Discutem-se as principais evidências de disfunção imune como imunodeficiência e autoimunidade.STUDY OBJECTIVE: The purpose of this study was to assess the extent of immune dysfunction in a well-defined group of epileptic patients: children with diagnosis of West syndrome (WS) or with transitions to another age-related EEG patterns, the multifocal independent spikes (MIS), and the slow spike-wave complexes (Lennox-Gastaut syndrome - LGS). Thus, WS was studied at different points of the natural evolutive history of the disease. METHOD: A group of 50 patients (33 with WS, 10 with LGS and 7 with MIS) and 20 age-matched healthy controls were submitted to enumeration of T lymphocyte subsets: CD1, CD3, CD4, CD8, CD4/CD8 ratio and lymphocyte proliferation assay to phytohaemagglutinin (PHA), in the presence of autologous and AB, homologous plasma. Dinitrochlorobenzene (DNCB) skin test sensitization was performed only in patients. Determinations of IgG, IgA, and IgM serum levels were compared to standard values for Brazilian population in different age ranges. RESULTS: Sensitization to DNCB showed absent or low skin reactions in 76% of the patients. High levels of IgG (45.7%) and IgM (61.4%), and lower levels of IgA (23.9%) were detected in the serum of the patients. Enumeration of lymphocyte subsets in peripheral blood showed: low CD3+ (p<0.05), low CD4+ (p<0.05), high CD8+ (p<0.01) and low CD4+ / CD8+ ratio (p<0.001). The proportion of CD1+ cells in the control group was less than 3%, while ranged between 6 and 11 % in 18% of the patients. The in vitro PHA-induced T cell proliferation showed significantly low blastogenic indices only when patients, cells were cultured in presence of their own plasma. No differences in blastogenic indices were observed when the cells of patients and controls were cultured with human AB plasma. CONCLUSION: The immunodeficiency in WS was mainly characterized by anergy, impaired cell-mediated immunity, altered levels of immunoglobulins, presence of immature thymocytes in peripheral blood and functional impairment of T lymphocytes induced by plasma inhibitory factors

Tumor necrosis factor-alpha in gestation and puerperium of women with gestational hypertension and pre-eclampsia

Problem High plasma levels of tumor necrosis factor-alpha (TNF-alpha) in pregnant women have been associated with the pathogenesis of pre-eclampsia (PE). This study evaluated TNF-alpha plasma levels and monocyte production in gestational hypertension (GH) and PE during gestation and at puerperium.Method of study This study included 128 women, of whom 20 were non-pregnant (NP) normotensive (NT), and 108 were pregnant: 36 NT, 27 with GH, and 45 with PE. Peripheral blood plasma was used for TNF-alpha and uric acid determination. TNF-alpha was determined in plasma and lipopolysaccharide (LPS)-stimulated and non-stimulated monocyte supernatants by L929 bioassay.Results Tumor necrosis factor-alpha and uric acid plasma levels were higher in PE than in GH pregnancies. In both hypertensive groups, these parameters positively correlated and were significantly more elevated than in NT and NP women. TNF-alpha plasma levels and monocyte production were higher in hypertensive than in NT women during gestation, and significantly decreased at puerperium. Although decreased, TNF-alpha release in LPS-stimulated PE monocytes, was still significantly higher than in the other pregnant groups.Conclusion In vivo monocyte activation in GH and PE pregnant women was characterized by in vitro TNF-alpha production. The fact that higher circulating concentrations of TNF-alpha and uric acid were observed in PE than in GH suggests an association with disease severity