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This study was made with the objective of reevaluating the colon denervation in chronic Chagas' disease. The diameters of neuron perikaryons of the myenteric plexus were measured on paraffin sections in a ring from the sigmoid in Chagas' disease patients, 17 with and 10 without megacolon and in 10 non-chagasic controls. All neurons were counted in ten en-echelon sections. Neuron hypertrophy only occurred in the group with megacolon, and the average increase in diameter was 69.3%. This could generate an error factor in the neuron count by increasing the probability of neurons being seen in a greater number of histological sections. The original result of the neuron count gave medians of 1264, 1961, and 2665 in the groups of chagasic patients with megacolon, without megacolon, and in the control, respectively. The denervation was greater than 55% in only seven megacolon cases (41.2%). After applying a correction factor, the median in the group with megacolon was 746, and the denervation was greater than 55% in 13 cases (76.5%). This occurrence demonstrates the need to apply a correction factor when the neuron count in chagasic megacolon is being evaluated and in the other pathologies where neuron hypertrophy may be found.

Background/Aims: Recent evidence shows a critical role of the CD4+ T cell with the Th1/Th2 paradigm as a possible effector mechanism in ischemia and reperfusion injury. We hypothesize that a polarized Th1 activation response may negatively influence the renal IRI through its relationship with chemokine production (MCP-1) and with a protective tissue response (HO-1). Methods: We subjected mice to renal ischemia for 45 min using IL-4 and IL-12 knockout C57BL/6. We then measured serum urea levels, performed histomorphometric analysis for tubular necrosis and regeneration, and evaluated the mRNA expression of HO-1, t-bet, Gata-3 and MCP-1 by real-time PCR at 24, 48 and 120 h after surgery. Results/Conclusions: The IL-4 knockout mice had a statistically significant rise in serum urea levels post IRI compared with control animals. The IL-12-deficient mice were not affected. The IL-4-deficient mice had a statistically significant increase in tubular injury and impairment in cell regeneration. The IRI in IL-4-deficient mice was accompanied by higher levels of HO-1, t-bet and later up-regulation of MCP-1. These findings suggest that the deleterious effects of the Th1 cell involve increased production of chemokines such as MCP-1.

Ischemia and reperfusion injury (IRI) is the main etiology of acute renal failure in native and transplanted kidneys. In the transplantation field, immunosuppressive drugs may play an additional role in acute graft dysfunction. Rapamycin may impair renal regeneration post IRI. Heme oxygenase 1 (HO-1) is a protective gene with anti-inflammatory and anti-apoptotic actions. We investigated whether HO-1 played a role in rapamycin-induced renal dysfunction in an established model of IRI. Rapamycin (3 mg/kg) was administered to mice before being subjected to 45 min of ischemia. Animals subjected to IRI presented with impaired renal function that peaked at 24 h (2.05+/-0.23 mg/dl), decreasing thereafter. Treatment with rapamycin caused even more renal dysfunctions (2.30+/-0.33 mg/dl), sustained up to 120 h after reperfusion (1.54+/-0.4 mg/dl), when compared to the control (0.63+/-0.09 mg/dl, P<0.05). Rapamycin delayed tubular regeneration that was normally higher in the control group at day 5 (68.53+/-2.30 vs 43.63+/-3.11%, P<0.05). HO-1 was markedly upregulated after IRI and its expression was even enhanced by rapamycin (1.32-fold). However, prior induction of HO-1 by cobalt protoporphyrin improved the renal dysfunction imposed by rapamycin, mostly at later time points. These results demonstrated that rapamycin used in ischemic-injured organs could also negatively affect post-transplantation recovery. Modulation of HO-1 expression may represent a feasible approach to limit rapamycin acute toxicity.