Effect of Influenza Virus Infection in a Murine Model of Asthma.

Respiratory virus infection is a major cause of asthma exacerbation. However, the underlying mechanisms of this exacerbation are unknown. Therefore, to determine the mechanisms, we examined the effect of influenza infection in a murine model of asthma. Mice were divided into four groups: the phosphate-buffered saline (PBS), house dust mite(HDM), influenza, and HDM/influenza groups. The influenza group and the HDM/influenza group were infected with influenza A virus. We measured airway resistance (Penh value), examined the lung tissue for pathology, and analyzed the cells and cytokines in bronchoalveolar lavage fluid (BALF) by ELISA. At 50 mg/mL methacholine, the HDM/influenza group showed a significantly higher Penh value than the PBS, HDM, and influenza groups. The number of neutrophils in BALF was higher in the HDM/influenza group than in the HDM group. A significantly greater number of lymphocytes and macrophages were detected in the HDM/influenza group than in the HDM group. IFN-γ and IL-1ß levels were higher in the HDM/influenza group than in the HDM group. IL-5 levels did not vary between the HDM and HDM/influenza groups, IL-10 was significantly lower in the HDM/influenza than in the HDM group. Chemokine (C-X-C motif) ligand 1 (CXCL1) and regulated upon activation, normal T cell expressed and secreted (RANTES) were higher in the HDM/influenza group than in the HDM group. In a murine model of asthma, influenza-induced airway inflammation appeared to be caused by simultaneous activation of neutrophilic and eosinophilic inflammation.

The effect of rhinovirus on airway inflammation in a murine asthma model.

PURPOSE: The aim of the present study was to investigate the differences in lower airway inflammatory immune responses, including cellular responses and responses in terms of inflammatory mediators in bronchoalveolar lavage fluid (BALF) and the airway, to rhinovirus (RV) infection on asthma exacerbation by comparing a control and a murine asthma model, with or without RV infection. METHODS: BALB/c mice were intraperitoneally injected with a crude extract of Dermatophagoides farinae (Df) or phosphate buffered saline (PBS) and were subsequently intranasally treated with a crude extract of Df or PBS. Airway responsiveness and cell infiltration, differential cell counts in BALF, and cytokine and chemokine concentrations in BALF were measured 24 hours after intranasal RV1B infection. RESULTS: RV infection increased the enhanced pause (Penh) in both the Df sensitized and challenged mice (Df mice) and PBS-treated mice (PBS mice) (P<0.05). Airway eosinophil infiltration increased in Df mice after RV infection (P<0.05). The levels of interleukin (IL) 13, tumor necrosis factor alpha, and regulated on activation, normal T cells expressed and secreted (RANTES) increased in response to RV infection in Df mice, but not in PBS mice (P<0.05). The level of IL-10 significantly decreased following RV infection in Df mice (P<0.05). CONCLUSION: Our findings suggest that the augmented induction of proinflammatory cytokines, Th2 cytokines, and chemokines that mediate an eosinophil response and the decreased induction of regulatory cytokines after RV infection may be important manifestations leading to airway inflammation with eosinophil infiltration and changes in airway responsiveness in the asthma model.

Evaluation of changes in random blood glucose and body mass index during and after completion of chemotherapy in children with acute lymphoblastic leukemia.

PURPOSE: Improved survival of patients with childhood acute lymphoblastic leukemia (ALL) has drawn attention to the potential for late consequences of previous treatments among survivors, including metabolic syndrome. In this study, we evaluated changes in 3 parameters, namely, random blood glucose, body mass index (BMI), and Z score for BMI (Z-BMI), in children with ALL during chemotherapy and after completion of treatment. METHODS: Patients newly diagnosed with ALL from January, 2005 to December, 2008 at Saint Mary's Hospital, The Catholic University of Korea, who completed treatment with chemotherapy only were included (n=107). Random glucose, BMI, and Z-BMI were recorded at 5 intervals: at diagnosis, before maintenance treatment, at completion of maintenance treatment, and 6 and 12 months after completion of maintenance treatment. Similar analyses were conducted on 2 subcohorts based on ALL risk groups. RESULTS: For random glucose, a paired comparison showed significantly lower levels at 12 months post-treatment compared to those at initial diagnosis (P<0.001) and before maintenance (P<0.001). The Z-BMI score was significantly higher before maintenance than at diagnosis (P<0.001), but decreased significantly at the end of treatment (P<0.001) and remained low at 6 months (P<0.001) and 12 months (P<0.001) post-treatment. Similar results were obtained upon analysis of risk group-based subcohorts. CONCLUSION: For a cohort of ALL patients treated without allogeneic transplantation or cranial irradiation, decrease in random glucose and Z-BMI after completion of chemotherapy does not indicate future glucose intolerance or obesity.

Neostigmine for the treatment of acute colonic pseudo-obstruction (ACPO) in pediatric hematologic malignancies.

BACKGROUND: Acute colonic pseudo-obstruction (ACPO) refers to dilatation of the colon and decreased bowel motility without evidence of mechanical obstruction. Neostigmine, an acetylcholinesterase inhibitor, has been used in patients in whom supportive therapy failed to resolve ACPO. Here, we report the results of administering neostigmine to treat ACPO in children with hematologic malignancies. METHODS: Between September 2005 and December 2009, 10 patients (8 male and 2 female) were diagnosed with ACPO at the Department of Pediatrics, Catholic University of Korea. Diagnosis of ACPO was based on typical clinical features as well as colonic dilatation found on abdominal CT imaging. Neostigmine was administered subcutaneously at a dosage of 0.01 mg/kg/dose (maximum 0.5 mg) twice daily for a maximum of 5 total doses. ACPO was determined to be responsive to neostigmine if the patient showed both stool passage and improvement of clinical symptoms. RESULTS: The study group included 8 acute lymphoblastic leukemia patients, 1 patient with malignant lymphoma, and 1 patient with juvenile myelomonocytic leukemia. The median age at ACPO diagnosis was 8.5 years (range, 3-14). Overall, 8 patients (80%) showed therapeutic response to neostigmine at a median of 29 hours after the initial administration (range, 1-70). Two patients (20%) showed side effects of grade 2 or above, but none complained of cardiovascular symptoms that required treatment. CONCLUSION: In this study, ACPO was diagnosed most often in late-childhood ALL patients. Subcutaneous neostigmine can be used to effectively treat ACPO diagnosed in children with hematologic malignancies without major cardiovascular complications.