Chlamydia pneumoniae Induces Interferon Gamma Responses in Peripheral Blood Mononuclear Cells in Children with Allergic Asthma.

Respiratory infections caused by Chlamydia pneumoniae have been associated with exacerbations of asthma. Cell-mediated immunity (CMI) is critical for maintaining immunity. We compared interferon (IFN)-γ responses in C. pneumoniae-infected peripheral blood mononuclear cells (PBMC) in paediatric patients ± asthma. Presence of C. pneumoniae was tested from asthma patients (N = 17) and non-asthmatic controls (N = 16) (PCR). PBMC were infected for 1 h ± C. pneumoniae AR-39 (MOI = 0.1) and cultured for 48 h. IFN-γ levels were measured in supernatants (ELISA). C. pneumoniae-IgG antibodies in serum were determined (MIF). All subjects tested negative for C. pneumoniae (PCR). C. pneumoniae-induced IFN-γ production in vitro was more prevalent in asthma compared with non-asthma; levels of IFN-γ were higher in asthma compared with non-asthma (P = 0.003). There was no association between recent respiratory infection and positive IFN-γ responses. These data show that C. pneumoniae modulates IFN-γ responses in patients with asthma, even in absence of active infection.

Chlamydia pneumoniae induces interleukin-12 responses in peripheral blood mononuclear cells in asthma and the role of toll like receptor 2 versus 4: a pilot study.

BACKGROUND: Chlamydia pneumoniae causes respiratory infection in adults and children, and has been associated with asthma exacerbations and induction of Immunoglobulin (Ig) E responses. We previously reported that C. pneumoniae enhances T helper (Th) 2 responses of peripheral blood mononuclear cells (PBMC) from asthmatic patients. It is likely that toll like receptor (TLR)-2 and TLR-4 mediate cytokine responses and host defense against C. pneumoniae. Thus, we sought to determine whether engagement of TLR-2 or TLR-4 may induce IL-12 production in our C. pneumoniae model. METHODS: PBMC (1.5 × 106) from asthmatic patients (N = 10) and non-asthmatic controls (N = 5) were infected or mock-infected for 1 h ± C. pneumoniae TW183 at a multiplicity of infection (MOI) = 1 and MOI = 0.1, and cultured for 48 h ± anti- TLR-2 and TLR-4 antibodies (Abs) (1 mg/mL). Interleukin (IL)-12 (48 h p.i.) and total IgE levels (day 10) were measured in supernatants (ELISA). RESULTS: High IgE levels were detected in supernatants of C. pneumoniae- infected PBMC from asthmatics on day 10, compared with mock-infected PBMC (p < 0.03). In contrast, IgE was not detected (<0.3 ng/mL) in either C. pneumoniae infected or mock-infected PBMC from non-asthmatics. IL-12 production by C. pneumoniae-infected asthmatic and non-asthmatic PBMC were similar. When anti-TLR4, but not anti-TLR2, was included in culture, IL-12 production by C. pneumoniae- infected asthmatic PBMC decreased. CONCLUSIONS: C. pneumoniae infection induces IgE production and modulates IL-12 responses in patients with asthma, which may be caused, in part, by differences in TLR-2 and TLR-4 stimulation.

Increased seroprevalence of Enterovirus 71 IgE antibodies in asthmatic compared with non-asthmatic children.

BACKGROUND: Asthma is a common pediatric chronic inflammatory airway disease. Respiratory viral infections are frequent infectious triggers for exacerbations of asthma. OBJECTIVE: We sought to determine whether Enterovirus 71 (EV71), a ubiquitous virus that causes systemic inflammatory responses in children but is not a known respiratory pathogen, can also serve as an infectious trigger for asthma. METHODS: Specific EV71 IgE and IgM antibodies (Abs), total serum IgE, and IL-2 and IL-4 cytokine levels in serum of asthmatic and non-asthmatic children (N = 42, ages 5-19; N = 35, ages 1-20, respectively) were measured (ELISA). RESULTS: Asthmatic children had higher EV71 IgE Ab levels than non-asthmatic (P < 0.001). Non-asthmatic children had significantly higher EV71 IgM Ab levels than asthmatic (P < 0.001). Despite low serum IgE levels of non-asthmatic, compared with asthmatic (P < 0.001), the non-asthmatic children produced significantly more IL-2 and IL-4 than asthmatic (P < 0.001; P < 0.001). The ages of the asthmatics, but not the non-asthmatics had a significant effect on the levels of EV 71 IgE Abs (P = 0.02; P = 0.356). A test of difference between these two slopes was significant. However, the ages of the non-asthmatic, but not the asthmatic children had a significant effect on the levels of EV 71 IgM Abs; a test of difference between these two slopes was significant. CONCLUSIONS: Increased specific EV71 IgE Ab responses may indicate that EV71 infection may also be an infectious trigger in asthma. However, the role of specific EV71 IgM Abs, Th2 cytokines, and age in non-asthmatic children should be further studied.

Disaster Olympics: A Model for Resident Education.

OBJECTIVES: The aim of this study was to describe an educational method teaching Disaster Medicine to American Emergency Medicine (EM) physicians and to evaluate knowledge attainment using this method. METHODS: This was an observational study using a pre-test and a post-test. A full-scale disaster exercise (FSE) was conducted at a large academic center with two hospitals in Brooklyn, New York (USA). Eighty-two EM residents (physicians in training, post medical school) participated in the study. Inclusion criteria for study participation was all EM residents training at the State University of New York (SUNY) Downstate at the time of the study. There were no exclusion criteria. The exercise was a disaster drill designed as "Olympic Games." Participants in the exercise took a pre-test and a post-test. The primary outcome of the study was the mean difference between pre-test and post-test scores of the study participants using independent sample t-tests. Secondary outcomes of the study were percent of critical actions met by the residents and the hospitals as measured by direct observation of trained study personnel during the exercise. RESULTS: Mean resident post-test scores were higher than pre-test scores to a degree that was statistically significant (62% versus 53%; P =.002). The residents' performances ranged from 48% to 63% of objectives met. The hospitals' performances met 50% to 100% of their objectives. CONCLUSION: The use of an Olympic Games format was an effective model for disaster education for physicians. The model allowed for evaluation of performance and protocols of participants and hospital systems, respectively, and may be used objectively to evaluate for areas of improvement. The Disaster Olympics drill was found to improve emergency preparedness knowledge in the population studied and may constitute a novel and efficacious methodology in disaster training. Daniel P , Gist R , Grock A , Kohlhoff S , Roblin P , Arquilla B . Disaster Olympics: a model for resident education. Prehosp Disaster Med. 2016;31(3):237-241.

Low-dose acyclovir for HSV-2 meningitis in a child.

A 7-y-old girl with genital herpes following sexual abuse presented with dysuria, fever and meningeal signs. Acyclovir (15 mg/kg/d for 10 d) was administered for severe genitourinary symptoms. The CSF culture was positive for HSV type 2. Complete resolution of all symptoms demonstrates that, as in adults, HSV-2 meningitis does not require high-dose or prolonged acyclovir therapy.

In vitro activity of a novel diaminopyrimidine compound, iclaprim, against Chlamydia trachomatis and C. pneumoniae.

The in vitro activities of iclaprim, a novel dihydrofolate reductase inhibitor, azithromycin, and levofloxacin were tested against 10 strains of Chlamydia trachomatis and 10 isolates of Chlamydia pneumoniae. For C. trachomatis and C. pneumoniae, the iclaprim MIC and minimal bactericidal concentration at which 90% of isolates were inhibited (MIC(90) and MBC(90)) were 0.5 micro g/ml, compared to an azithromycin MIC(90) and MBC(90) of 0.125 micro g/ml and levofloxacin MIC(90)s and MBC(90)s of 1 micro g/ml for C. trachomatis and 0.5 micro g/ml for C. pneumoniae.

SV40 T/t-antigens sensitize mammary gland epithelial cells to oxidative stress and apoptosis.

As shown recently, the SV40 T/t-antigens (T/t-ag) exert a strong apoptotic activity in mouse mammary gland epithelial cells (ME-cells) leading to premature gland involution at late pregnancy. This high spontaneous cell death rate (20%) is also maintained in T/t-ag positive ME-tissue culture cell lines (e.g., 8/61-A), but not in those ME-cells that have switched off the SV40 T/t-transgene expression. In this study, we demonstrate for the first time that the T/t-ag sensitize ME-cells to oxidative stress leading to apoptosis. Treatment of the 8/61-A ME-cells with catalase, a scavenger of H2O2, completely blocked spontaneous cell death, which was linked to downregulation of caspase-3 activity. Furthermore, exposure of the cells to low concentrations of H2O2 highly increased the apoptosis rate. These findings suggest that the T/t-ag positive ME-cells contain either elevated levels of reactive oxygen species or reduced antioxidant activities. During spontaneous and H2O2-induced apoptosis, the activity of caspase-3 is significantly increased. In addition, the 8/61-A cells accumulated p21 and Bax proteins while the level of the anti-apoptotic protein Bcl-2 decreased implying a posttranscriptional regulation of apoptosis.