Effect of treatment with cyclophosphamide in low doses upon the onset of delayed type hypersensitivity in mice chronically infected with Trypanosoma cruzi: involvement of heart interstitial dendritic cells

Acute infection with Trypanosoma cruzi results in intense myocarditis, which progresses to a chronic, asymptomatic indeterminate form. The evolution toward this chronic cardiac form occurs in approximately 30% of all cases of T. cruzi infection. Suppression of delayed type hypersensitivity (DTH) has been proposed as a potential explanation of the indeterminate form. We investigated the effect of cyclophosphamide (CYCL) treatment on the regulatory mechanism of DTH and the participation of heart interstitial dendritic cells (IDCs) in this process using BALB/c mice chronically infected with T. cruzi. One group was treated with CYCL (20 mg/kg body weight) for one month. A DTH skin test was performed by intradermal injection of T. cruzi antigen (3 mg/mL) in the hind-footpad and measured the skin thickness after 24 h, 48 h and 72 h. The skin test revealed increased thickness in antigen-injected footpads, which was more evident in the mice treated with CYCL than in those mice that did not receive treatment. The thickened regions were characterised by perivascular infiltrates and areas of necrosis. Intense lesions of the myocardium were present in three/16 cases and included large areas of necrosis. Morphometric evaluation of lymphocytes showed a predominance of TCD8 cells. Heart IDCs were immunolabelled with specific antibodies (CD11b and CD11c) and T. cruzi antigens were detected using a specific anti-T. cruzi antibody. Identification of T. cruzi antigens, sequestered in these cells using specific anti-T. cruzi antibodies was done, showing a significant increase in the number of these cells in treated mice. These results indicate that IDCs participate in the regulatory mechanisms of DTH response to T. cruzi infection.

Enfermedad inflamatoria intestinal y cirugía / Intestinal inflamatory disease and sugery

El objetivo de este artículo es divulgar el rol actual de la cirugía en la enfermedad inflamatoria crónica del intestino, considerando que se han consolidado avances significativos en los últimos 20 a 25 años y tomando en cuenta que no menos del 20 a 45 por ciento de los pacientes con colitis ulcerativa idiopática (CUI), y del 90 por ciento de los portadores de enfermedad de Crohn (EC), requerirán una operación, debido a su condición, durante el transcurso de sus vidas. Se exponen las indicaciones quirúrgicas, urgentes y electivas, en ambas enfermedades, destacando dentro de las primeras, el megacolon tóxico, perforación y hemorragia masiva; y en las electivas, el fracaso o imposibilidad de seguir el tratamiento médico, la aparición de displasia en la CUI; cáncer, tanto en la CUI como en la EC; y las estenosis y fístulas sintomáticas en el EC. Se comenta el tipo de operación más apropiada en cada situación, destacando la colectomía subtotal como operación de urgencia estándar de las afecciones colónicas agudas, y las resecciones mínimas, e incluso estenoplastía, en la EC del intestino delgado. La operación electiva ideal en la CUI es la proctolectomía restauradora con reservorio ileal y anastomosis entre el reservorio y el ano. Tal intervención reseca toda la mucosa colo-rectal, eliminando el órgano de choque, al mismo tiempo que preserva la función esfinteriana. Ella está contraindicada en situaciones de urgencia, al igual que en la colitis de la EC. Los pacientes sometidos a un reservorio pueden lograr una excelente calidad de vida, pero a costa de una considerable morbilidad, aunque con una muy baja letalidad.

The effect of methotrexate and azathioprine on the serum levels of IgA-alfa1-antitrypsin complex in juvenile chronic arthritis

In the present study we investigated the influence of methotrexate (MTX) and azathioprine (AZA) on the serum levels of the IgA-alpha1-antitypsin (IgA-AT) complex in patients with the systemic form of juvenile chronic arthritis (JCA). Fifty-six JCA patients (22 treated with MTX, 18 treated with AZA, and 16 not treated with any immuno-suppressive agent) were enrolled in the study. MTX dosage ranged from 0.3 to 0.5 mg kg(-1) week(-1) while AZA was given daily at an average dose of 1 mg/kg. MTX was given for 13 months (SD = 7 months) whereas AZA for 11 months (SD = 6 months). The average value of the complex was higher in JCA patients than in both control groups (0.74 + 0.73 U vs 0.37 + 0.13 U (control children), P<0.001 and vs 0.23 + 0.12 U (control adults), P<0.001). Values exceeding the normal range were found in twenty-two JCA patients (39.4 percent). Serum IgA-AT level was lowest in the MTX group compared to AZA and non-treated patients (0.56 + 0.24 U, 0.76 + 0.43 U, 0.95 + 0.52 U, respectively, P<0.05). IgA values exceeding normal levels for age were found in 14 percent of the patients. A correlation between the levels of the IgA-AT complex and C-reactive protein (r = 0.43, P<0.01), alpha1-acid-glycoprotein (r = 0.45, P<0.01), alpha1-antichymotrypsin (r = 0.52, P<0.01), alpha1-antitrypsin (r = 0.40, P<0.01) and IgA (r = 0.56, P<0.01) was established.