Reconsideration of histopathology and ultrastructural aspects of the human liver in yellow fever

Yellow fever is a re-emerging infectious disease that currently is at risk of urbanization due to the advance of the Aedes aegypti vector. The disease affects about 200,000 individuals annually, mainly in tropical Africa and South America. It causes severe disease involving especially the liver, with lesions characterized by midzonal steatosis, apoptosis and lytic necrosis of the hepatocytes. Quantitative histological and immunohistochemical analysis of 53 human hepatic samples demonstrated apoptosis, steatosis and lytic necrosis of hepatocytes with midzonal pattern. No substantial alterations and reticular network were observed. The inflammatory infiltrate consisted of mononuclear cells and intensity was minimal or moderate, disproportionate to the intense death of the hepatocytes. Hepatic damage in yellow fever resulted mainly from a massive death of hepatocytes due to apoptosis and to a lesser extent due to lytic necrosis. It is recommended that therapeutic regimens for serious cases should include measures to protect against apoptosis. (c) 2005 Elsevier B.V. All rights reserved

The inflammasome in leprosy skin lesions: an immunohistochemical evaluation

Luciana Mota Silva,1 Jorge Rodrigues de Sousa,2,3 Kelly Emi Hirai,1 Leônidas Braga Dias Jr,1 Ismari Perini Furlaneto,1 Francisca Regina Oliveira Carneiro,1 Tinara Leila de Souza Aarão,1 Mirian Nacagami Sotto,4,5 Juarez Antonio Simões Quaresma1–3,5 1Center of Biological and Health Science, State University of Para, Belem, Brazil; 2Tropical Medicine Center, Federal Do Para University, Belem, Brazil; 3Evandro Chagas Institute, Ministry of Health, Ananindeua, Brazil; 4School of Medicine, Sao Paulo University, Sao Paulo, Brazil; 5Tropical Medicine Institute, Sao Paulo University, Sao Paulo, Brazil Objective: Leprosy is a chronic infectious disease presenting with a spectrum of clinical manifestations that correspond to the type of immune response that develops in the host. Factors that may be involved in this process include inflammasomes, cytosolic proteins responsible for the activation of caspase 1, IL-1β and IL-18 secretion, and induction of a type of death called pyroptosis.Patients and methods: We evaluated the expression of inflammasome markers (nucleotide-binding oligomerization domain-like receptor containing pyrin domain 1 [NLRP1], nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 [NLRP3], caspase 1, IL-1β, and IL-18) by immunohistochemistry in 43 samples of skin lesions of leprosy patients from the groups indeterminate (I) leprosy (13 patients), tuberculoid (TT) leprosy (15 patients), and lepromatous leprosy (LL; 15 patients).Results: The evaluated markers were most upregulated in LL lesions, followed by lesions of TT leprosy and I leprosy. Differences were statistically significant between the I leprosy and LL leprosy forms and between the I leprosy and TT leprosy forms. Positive and significant correlations were found between IL-18 and caspase 1 in LL (r=0.7516, P=0.0012) and TT leprosy (r=0.7366, P=0.0017). In I leprosy, correlations were detected between caspase 1 and IL-1β (r=0.6412, P=0.0182), NLRP1 and IL-18 (r=0.5585, P=0.473), NLRP3 and IL-18 (r=0.6873, P=0.0094), and NLRP1 and NLRP3 (r=0.8040, P=0.0009).Conclusion: The expression of inflammasome markers in LL lesions indicates the ineffectiveness of this protein complex in controlling the infection. Caspase 1 may be involved in the pyroptotic cell death in the lepromatous form of the disease. Inflammasomes may act together in the initial phase of I leprosy; this phenomenon may influence the clinical outcome of the disease. Keywords: IL-1β, NLRP, Mycobacterium leprae, immune response, pyroptosi

In situ detection of Chlamydia pneumoniae, C. trachomatis, and cytokines among cardiovascular diseased patients from the Amazon region of Brazil

Larissa S Freitas,1 Núbia Caroline C Almeida,1 Maria Alice Freitas Queiroz,1 Marcelo M Zaninotto,2 Hellen T Fuzii,3 Alfredo Ribeiro-Silva,4 Antonio CR Vallinoto,1 Marluísa OG Ishak,1 Juarez AS Quaresma,3 Ricardo Ishak1 1Virus Laboratory, Institute of Biological Sciences, Federal University of Para, 2Hospital of Clinic Gaspar Viana, 3Laboratory of Immunopathology, Nucleus of Tropical Medicine, Federal University of Para, Belém, 4Departament of Pathology, Medical School of Ribeirão Preto, University of Sao Paulo, São Paulo, Brazil Background: Chronic coronary artery disease has been associated, as a consequence of the local inflammatory reaction with previous or persistent infection with Chlamydia pneumoniae, which led to the investigation of the association of cardiovascular disease and previous infection with C. trachomatis and the role of cytokine profile (in situ) markers in the vascular system tissues. Methods: Sixty-nine biopsies were collected for immunohistochemical analysis for the presence of IL-6, IL-8, TNF-α, IFN-γ, TGF-β, and IL-10, in 16 fragments from atheromatous plaques, 32 aorta fragments, and 21 valve fragments, using a tissue microarray technique for paraffin embedded tissues. Results: Most patients undergoing revascularization surgery were men >50 years, while those undergoing valve replacement were mostly women <50 years. TNF-α was the most prevalent marker, detected in 91.7% (55/60) of the samples. The mean percent area stained was greater in patients infected with C. pneumoniae (3.81% vs 1.92%; p=0.0115) and specifically in the aorta (4.83% vs 2.25%; p=0.0025); C. trachomatis infection was higher in valves, and C. pneumoniae in plaques, both without statistical significance. There was no significant difference in the cytokine staining profile between patients previously infected with both species and uninfected patients. Conclusion: Although there was no difference in the cytokine profile between patients previously infected with both species of Chlamydia, and uninfected patients, the presence of the bacteria antigens in the three biological specimens indicates it is important to focus on the role of C. trachomatis. It is necessary to improve the understanding of the natural history of chronic coronary artery disease and the clinical history of the patients and cytokine dynamics in cardiac disease in the presence or absence of infectious agents. Keywords: Chlamydia, C. pneumoniae, C. trachomatis, atherosclerosis, cytokine