BackgroundThe tubule-interstitial fibrosis is the hallmark of progressive renal disease and is strongly associated with inflammation of this compartment. Heme-oxygenase-1 (HO-1) is a cytoprotective molecule that has been shown to be beneficial in various models of renal injury. However, the role of HO-1 in reversing an established renal scar has not yet been addressed.AimWe explored the ability of HO-1 to halt and reverse the establishment of fibrosis in an experimental model of chronic renal disease.MethodsSprague-Dawley male rats were subjected to unilateral ureteral obstruction (UUO) and divided into two groups: non-treated and Hemin-treated. To study the prevention of fibrosis, animals were pre-treated with Hemin at days -2 and -1 prior to UUO. To investigate whether HO-1 could reverse established fibrosis, Hemin therapy was given at days 6 and 7 post-surgery. After 7 and/or 14 days, animals were sacrificed and blood, urine and kidney tissue samples were collected for analyses. Renal function was determined by assessing the serum creatinine, inulin clearance, proteinuria/creatininuria ratio and extent of albuminuria. Arterial blood pressure was measured and fibrosis was quantified by Picrosirius staining. Gene and protein expression of pro-inflammatory and pro-fibrotic molecules, as well as HO-1 were performed.ResultsPre-treatment with Hemin upregulated HO-1 expression and significantly reduced proteinuria, albuminuria, inflammation and pro-fibrotic protein and gene expressions in animals subjected to UUO. Interestingly, the delayed treatment with Hemin was also able to reduce renal dysfunction and to decrease the expression of pro-inflammatory molecules, all in association with significantly reduced levels of fibrosis-related molecules and collagen deposition. Finally, TGF-β protein production was significantly lower in Hemin-treated animals.ConclusionTreatment with Hemin was able both to prevent the progression of fibrosis and to reverse an established renal scar. Modulation of inflammation appears to be the major mechanism behind HO-1 cytoprotection.

Primeira submissão em 09/10/08 Última submissão em 16/12/08 Aceito para publicação em 20/12/08 Publicado em 20/12/08 artigo origiNal original article

The kidney transplant is the main therapeutic alternative for end-stage kidney disease, and rejection is a major complication. The expression of proinflammatory cytokines is related to graft loss, whereas anti-inflammatory cytokines are associated with graft protection. The objective of this study is to evaluate the "in situ" expression of cytokines T helper 1 (tumor necrosis factor α [TNF-α]), T helper 17 (interleukin 17 [IL-17]), and regulatory T cell (transforming growth factor β [TGF-β]) and the expression of forkhead box P3 (FoxP3) in allograft kidney. We evaluated in situ expression of cytokines in allograft kidney under rejection process by indirect immunohistochemistry. Eighteen renal graft biopsies were from patients with episodes of rejection. The in situ expression of IL-17, TNF-α, and TGF-β was significantly higher in patients with acute rejection when compared with the control group. In contrast, analysis of FoxP3 expression showed few positive cells in patients with acute rejection compared with the control group. The results suggest that the expression of proinflammatory cytokines (IL-17 and TNF-α) contributes to the mechanisms of kidney transplant rejection. The increase in TGF-β expression might be an attempt to establish a process of immunoregulation or even to induce higher production of IL-17. The last hypothesis is supported by the observation of a reduced expression of FoxP3 and elevated levels of IL-17.

Transplanted organs may act as a route of transmission of infectious diseases, such as Chagas' disease. The aim of this study was to describe the transmission of the Trypanosoma cruzi through a renal transplant and the anatomo-clinical evolution of the patient after treatment with benzonidazole. The patient was a 31-year-old white male from the State of Minas Gerais in Brazil. He had renal failure secondary to diabetes and later received a kidney from a cadaveric donor. The patient was undergoing immunosuppression therapy with azathioprine, cyclosporine A, and prednisone. After the transplant, he developed an acute phase of Chagas' disease and complications from diabetes and died 2 months later. In the autopsy, T cruzi amastigotes were found in the transplanted kidney, heart, bladder, liver, and pancreas. An important reduction in the parasitemia was obtained through the treatment of the infection with benzonidazole; however, the patient died due to complications from diabetes associated with tissue lesions caused by T cruzi.

-The aim of this paper was to describe the occurrence and morphology of neurocysticercosis (NCC) in autopsies. We revised 2218 autopsies performed at the School Hospital from Federal Unversity of Triangulo Mineiro, 1970Mineiro, -2003. Data referring to age, gender and color of patients were reported and NCC was microscopically and macroscopically analyzed. We found 53 (2.4%) NCC cases. The mean age was 50 years old, 34 (64.1%) individuals were male and 36 (67.9%) white. Macroscopically, 17 cysticerci were analyzed. The most frequent location was meningocortical in 12 (70.6%) cases. Microscopically, the cysticerci presented an ovoid shape, containing the larvae preserved in 4 (23.5%) cases or in destruction degrees in 13 (76.5%) cases. Therefore, in NCC was found several general pathologic processes (necrosis, interstitial deposits, fibrosis, gliosis, inflammation) amongst which are highlighted beta-fibrillose in 13 (76.5%) cases associated to inflammatory process in 16 (94.1%) cases caused by the parasite, not yet related to NCC, and calcification present in viable and destruction parasites.KEY WORDS: autopsy neurocysticercosis, general pathologic processes, cysticercosis, central nervous system. Aspectos anatomopatológicos da neurocisticercose em pacientes autopsiadosRESUMO -O objetivo desse trabalho foi descrever ocorrência e morfologia da neurocisticercose (NCC) autópsias. Revisou-se 2218 autópsias realizadas no Hospital Escola da Universidade Federal do Triângulo Mineiro (UFTM), 1970-2003. Registrou-se idade, gênero e cor dos pacientes, analisou-se macroscopia e microscopia da NCC. Encontrou-se 53 (2,4%) casos de NCC. A média das idades foi 50 anos, sendo 34 (64,1%) do sexo masculino e 36 (67,9%) brancos, não havendo diferença significante na comparação da idade, gênero e cor dos pacientes. Analisou-se macroscopicamente 17 cisticercos. A localização mais comum foi a meningocortical em 12 (70,6%) casos. Microscopicamente, os cisticercos apresentaram forma oval contendo a larva íntegra em 4 (23,5%) casos ou em grau de destruição em 13 (76,5%) casos. Portanto, na NCC foram verificados vários processos patológicos gerais (necrose, depósitos intersticiais, fibrose, gliose, inflamação) destacando-se: beta-fibrilose em 13 (76,5%) casos associada ao processo inflamatório em 16(94,1%) casos causado pelo parasito, ainda não relatada na NCC, e calcificação presente no parasito viável e em destruição. PALAVRAS-CHAVE: autópsia, neurocisticercose, processos patológicos gerais, cisticercose, sistema nervoso central.Human cysticercosis occurs due to ingestion, with contaminated food, of eggs containing oncospheres. In the intestinal portion the oncospheres hatch, penetrate in the intestinal wall and disseminate through blood and lymph vessels until it gets to several tissues, however with great tropism to the central nervous system (CNS) 1,2 . Neurocysticercosis (NCC) is characterized by presenting several clinic manifestations 3 . The polymorphism of its clinic manifestations depends not only on its localization ...

Both chagasic groups present an autonomic impairment using linear methods. The nonlinear methods revealed that the ChHD group had a higher cardiovascular risk. Serum cytokine concentrations between chagasic patients were similar. However, ChHD showed higher concentrations of IL-10 and lower of IFN-γ, suggesting some established process of immune regulation.

No abstract

The aim of the present study was to assess the effects of an anticholinesterase agent, pyridostigmine bromide (Pyrido), on experimental chronic Chagas heart disease in mice. To this end, male C57BL/6J mice noninfected (control:Con) or chronically infected (5 months) with Trypanosoma cruzi (chagasic:Chg) were treated or not (NT) with Pyrido for one month. At the end of this period, electrocardiogram (ECG); cardiac autonomic function; heart histopathology; serum cytokines; and the presence of blood and tissue parasites by means of immunohistochemistry and PCR were assessed. In NT-Chg mice, significant changes in the electrocardiographic, autonomic, and cardiac histopathological profiles were observed confirming a chronic inflammatory response. Treatment with Pyrido in Chagasic mice caused a significant reduction of myocardial inflammatory infiltration, fibrosis, and hypertrophy, which was accompanied by a decrease in serum levels of IFNγ with no change in IL-10 levels, suggesting a shift of immune response toward an anti-inflammatory profile. Lower nondifferent numbers of parasite DNA copies were observed in both treated and nontreated chagasic mice. In conclusion, our findings confirm the marked neuroimmunomodulatory role played by the parasympathetic autonomic nervous system in the evolution of the inflammatory-immune response to T. cruzi during experimental chronic Chagas heart disease in mice.