Spironolactone, but not enalapril, potentiates hypoxia-inducible factor-1 alpha and Ets-1 expression in newborn rat kidney.

Hypoxia is regarded as an important physiological factor that controls nephrogenesis. We investigated whether the renin-angiotensin-aldosterone system (RAAS) affects hypoxia-related target genes in developing kidneys. Newborn rat pups were treated with enalapril (30 mg/kg/d) or spironolactone (200 mg/kg/d) for 7 days. Tissue hypoxia was assessed by the uptake of a hypoxyprobe-1, pimonidazole (200 mg/kg), and the expression of hypoxia-responsive genes. In the enalapril group, hypoxia-inducible factor (HIF)-1alpha, HIF-2alpha, and Ets-1 protein expression were not changed, compared to the control group. In the spironolactone group, HIF-1alpha and Ets-1 protein expression were significantly increased by immunoblots and immunohistochemistry, whereas HIF-2alpha protein expression was not changed, compared to the control group. In the enalapril group, the immunoactivity of pimonidazole was not significantly different from that of the controls. However, in the spironolactone group, pimonidazole staining demonstrated that the cortex and medulla underwent severe hypoxia. In summary, our data showed that aldosterone inhibition in the developing kidney augmented the hypoxic responses, and up-regulated the expression of key mediators of hypoxia including HIF-1alpha and Ets-1. Angiotensin II inhibition did not affect hypoxia-related alterations in the developing kidney. The components of RAAS may differentially modulate renal hypoxia and its related target genes in the developing rat kidney.

Acute tubulointerstitial nephritis complicated by Salmonella enteritidis gastroenteritis.

Invasive non-typhoidal salmonellosis may occur in otherwise healthy children. We report an immunocompetent 3-year-old boy with Salmonella enteritidis gastroenteritis complicated by acute tubulointerstitial nephritis who presented with fever, bloody diarrhea and gross hematuria. This case is the first report of non-typhoidal salmonellosis associated with biopsy-proven tubulointerstitial nephritis in a child.

Churg-Strauss syndrome in a child with IgA nephropathy.

Churg-Strauss syndrome (CSS) is a rare systemic vasculitis associated with asthma and eosinophilia. Withdrawal of corticosteroids in asthmatic patients is known to be a powerful trigger for the development of CSS. Renal involvement in patients with CSS is commonly manifested as antineutrophil cytoplasm antibody-associated necrotizing crescentic glomerulonephritis, however, concomitant CSS and the nephrotic syndrome or IgA nephropathy are rare. We report a 12-year-old boy with CSS associated with IgA nephropathy that developed while tapering oral steroids. The patient had a history of the nephrotic syndrome and asthma.

Albumin versus normal saline for dehydrated term infants with metabolic acidosis due to acute diarrhea.

UNLABELLED: To compare the efficacy of albumin to normal saline (NS) for initial hydration therapy for dehydrated term infants with severe metabolic acidosis due to acute diarrhea. STUDY DESIGN: We randomized 33 infants presenting with moderate-to-severe dehydration and metabolic acidosis (pH <7.25 or base excess (BE) <-15) into two groups, an albumin group (n=15) and a NS group (n=18). For initial hydration treatment, the albumin group received 5% albumin (10 ml kg(-1)), whereas the NS group received NS (10 ml kg(-1)). RESULT: After 3 h of treatment, both groups improved. However, the magnitude of improvement in the pH, BE and HCO(3)(-) levels were not different in comparisons between these two groups. In addition, there were no differences either in the body weight and weight gain 4 days after treatment or in the length of hospital stay. CONCLUSION: Albumin was not more effective than NS for initial hydration treatment of dehydrated term infants with metabolic acidosis due to acute diarrhea.

Immunohistochemical characterization of cellular infiltrate in nasal polyp from aspirin-sensitive asthmatic patients.

BACKGROUND: The immunopathologic mechanism of nasal polyp in aspirin-sensitive asthma remains to be further defined. OBJECTIVE: To characterize the features of the inflammatory cellular infiltrate in the nasal polyp tissue from aspirin-sensitive asthmatic patients. METHODS: We have taken nasal polyp tissue during nasal polyp resection from 13 aspirin-sensitive asthma, 6 allergic, and 12 non-allergic subjects. Immunohistochemistry was employed to stain and enumerate the individual inflammatory cell types using monoclonal antibodies against tryptase (AA1) to identify mast cells, against secreted forms of eosinophil cationic protein (EG2), to identify activated eosinophils, against neutrophil elastase (NE) for neutrophils and against T cell surface markers (CD3) to identify total T cells. RESULTS: There were no significant differences in AA1 + cells among three groups (P>.05). EG2 + cells tended to be higher in ASA-sensitive asthmatic patients than in allergic and non-allergic subjects, but no statistical significance was observed. NE+ cells were found in most subjects of the three groups and their numbers were significantly higher in allergic subjects than in aspirin-sensitive asthma (P<.05). Some patients had CD3+ cells with no statistical significance among the three groups. Significant correlation was found in numbers between NE+ cell and AA1+ cell (r=.44, P=.01), and between NE+ cell and EG2+ cell (r=.40, P=.02). CONCLUSION: These findings suggested that major effector cells such as mast cells and eosinophils might be placed in the center of the inflammatory response of nasal polyps, regardless of their association with aspirin sensitivity.

Neutrophil infiltration and release of IL-8 in airway mucosa from subjects with grain dust-induced occupational asthma.

BACKGROUND: The immuno-pathological mechanism for occupational asthma induced by grain dust (GD) remains to be clarified. There have been few reports suggesting the involvement of neutrophils inducing bronchoconstriction after inhalation of GD. OBJECTIVE: To further understand the role of neutrophil in the pathogenesis of GD-induced asthma. MATERIALS AND METHODS: We studied the phenotype of leucocytes of the bronchial mucosa in patients with GD-induced asthma. Bronchial biopsy specimens were obtained by fibreoptic bronchoscopy from six subjects with GD-induced asthma. Six allergic asthma patients sensitive to house dust mite were enrolled as controls. Bronchial biopsy specimens were examined by immunohistochemistry with a panel of monoclonal antibodies to tryptase-containing mast cell (AA1), activated eosinophil (EG2), pan T-lymphocyte (CD3) and neutrophil elastase (NE). Induced sputum was collected before and after the GD-bronchoprovocation test. The IL-8 level in the sputum was measured using ELISA. RESULTS: There was a significant increase in the number of AA1+ and NE+ cells in bronchial mucosa of GD-induced asthma, compared with those of allergic asthma (P=0.01, P=0.01, respectively). No significant differences were observed in the number of EG2+ and CD3+ cells (P = 0.13, P=0.15, respectively). IL-8 was abundant in the sputum of all GD-induced asthma patients and significantly increased after the bronchial challenges compared with the baseline value (P = 0.03). CONCLUSION: These findings support the view that neutrophil recruitment together with mast cells may contribute to the bronchoconstriction induced by GD. A possible involvement of IL-8 was suggested.

Immunohistochemical characterization of the cellular infiltrate in airway mucosa of toluene diisocyanate (TDI)-induced asthma: comparison with allergic asthma.

Toluene diisocyanate (TDI) is the most prevalent agent in occupational asthma (OA) in Korea. The immuno-pathologic mechanism for TDI-induced bronchoconstriction remains to be clarified. We studied the immunohistochemical finding of inflammatory cells in bronchial mucosa in subjects with TDI-induced asthma. Fiberoptic bronchial biopsy specimens were obtained from nine subjects with TDI-induced asthma. Six allergic asthma sensitive to house dust mite were enrolled as controls. Bronchial biopsy specimens were examined by immunohistology with a panel of monoclonal antibodies to mast cell tryptase (AA1), secretary form of eosinophil cationic protein (EG2), pan T-lymphocyte (CD3) and neutrophil elastase (NE). There was a significant increase in the number of AA1+, EG2+ and NE+ cells in TDI-induced asthma compared to those of allergic asthma (p=0.02, p=0.04, p=0.03, respectively). No significant differences were observed in the number of CD3+ cells (p=0.27). These findings support the view that neutrophil recruitment together with eosinophil and mast cell, may contribute to the bronchoconstriction induced by TDI.