Isolated cutaneous response to granulocyte-monocyte colony stimulating factor in fatal idiopathic disseminated Bacillus-Calmette-Guerin infection

Severe disseminated Bacillus-Calmette-Guerin (BCG) infection is very rare and has been regarded as idiopathic when no immunodeficiency is present. This entity seems to be due to several new types of inherited abnormalities in the pathways important in defence against Mycobacteria. Although improvement with interferon-γ (IFN-γ) has been reported in some patients, to our knowledge there are no reports on the effect of other cytokines in the treatment of these patients. We report here the clinical response to IFN-γ and granulocyte-monocyte colony stimulating factor (GM-CSF) treatment in a patient with idiopathic disseminated BCG infection who failed to respond to multiple antimycobacterial agents. The patient showed partial and transitory response to IFN-γ, however, GM-CSF treatment led to rapid improvement of skin lesions within 2 weeks without any effect on the progression of the disease in the other organ systems. Conclusion The response of idiopathic disseminated Bacillus-Calmette-Guerin infection to granulocyte-monocyte colony stimulating factor treatment was limited to cutaneous lesions. Granulocyte-monocyte colony stimulating factor may have acted to promote wound healing or the levels of this factor achieved in other affected organs may have been inadequate. Received: 26 January 1999 / Accepted: 1 July 1999     

Paraoxonase, total antioxidant activity and peroxide levels in marasmic children: relationships with leptin

OBJECTIVES: The aim of this study was to investigate the oxidant/antioxidant status, paraoxonase (PON) activity and leptin levels in children with marasmic malnutrition. DESIGN AND METHODS: Thirty marasmic children (age 14.4+/-10.3 months) and 28 control subjects were included. Plasma PON activity, total antioxidant activity (TAO), total peroxide (TPX) and leptin levels were measured. RESULTS: Malnourished children had significantly lower leptin (3.6+/-1.1 vs. 11.8+/-4.5 ng/mL, P<0.001), PON activity (66.4+/-28.6 vs. 221.3+/-31.6 IU/L, P<0.001) and TAO (1.44+/-0.12 vs. 2.45+/-0.61 mmol Trolox equiv/L, P<0.001); and higher TPX (15.6+/-6.4 vs. 5.9+/-1.9 micromol/L, P<0.001) values than in controls. Significant negative correlation was found between PON and TPX (P=0.040) and positive correlation between TAO and BMI (P=0.034) in patients. No significant correlation was found between leptin and oxidant/antioxidant parameters (P>0.05). CONCLUSIONS: Children with marasmic malnutrition had increased pro-oxidant and decreased antioxidant status. Extent of oxidative stress increases with malnutrition severity. Antioxidants could be given during nutritional rehabilitation.     

Arsenic trioxide induces apoptosis in peripheral blood T lymphocyte subsets by inducing oxidative stress: a role of Bcl-2

Arsenic trioxide (As(2)O(3)) has been used successfully in the treatment of acute promyelocytic leukemia. However, effects of As(2)O(3) in normal peripheral blood T cells have not been studied in detail. The purpose of this study was to investigate whether As(2)O(3) would induce apoptosis in normal T cells and therefore may have immunosuppressive side effects. Apoptosis was measured by terminal deoxynucleotidyl transferase-mediated nick end labeling assay, caspase activation by flow cytometry and colorimetric assay, mitochondrial transmembrane potential (deltapsi(m)), intracellular reactive oxygen species (ROS), and intracellular reduced glutathione (GSH) by flow cytometry. The release of cytochrome c and apoptosis-inducing factor (AIF) from the mitochondria was measured by confocal microscopy, and the expression of molecules regulating apoptosis was measured by Western blotting. As(2)O(3), at clinically achievable therapeutic concentrations, induces apoptosis in peripheral blood T cells. As(2)O(3)-induced apoptosis was associated with reduced deltapsi(m), enhanced generation of intracellular ROS, decreased levels of intracellular GSH, release of cytochrome c and AIF from the mitochondria, activation of caspases, down-regulation of Bcl-2 and Bcl-x(L), and up-regulation of Bax expression. In addition, exogenous GSH protected lymphocytes from As(2)O(3)-induced apoptosis. Furthermore, overexpression of Bcl-2 inhibited As(2)O(3)-induced apoptosis and blocked depolarization of deltapsi(m), generation of ROS, and release of both cytochrome c and AIF. These data indicate that As(2)O(3) induces apoptosis in T cells by enhancing oxidative stress and that Bcl-2 appears to play a major role in As(2)O(3)-induced apoptosis.     

Oleanolic acid and ursolic acid derived from Cornus officinalis Sieb. et Zucc. suppress epidermal growth factor- and phorbol ester-induced MUC5AC mucin production and gene expression from human airway epithelial cells

In this study, the effects of oleanolic acid and ursolic acid on MUC5AC mucin production and gene expression induced by epidermal growth factor (EGF) and phorbol 12‐myristate 13‐acetate (PMA) from human airway epithelial cells were investigated. Confluent NCI‐H292 cells were pretreated with each agent for 30 min and then stimulated with EGF and PMA for 24 h, respectively. MUC5AC mucin gene expression and mucin protein production were measured by RT‐PCR and ELISA. Oleanolic acid and ursolic acid were found to inhibit the production of MUC5AC mucin protein induced by EGF and PMA, and both compounds also inhibited the expression of MUC5AC mucin gene induced by EGF and PMA. These results suggest that oleanolic acid and ursolic acid can regulate mucin gene expression, and production of mucin protein, by directly acting on airway epithelial cells. Copyright © 2011 John Wiley & Sons, Ltd.