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The accumulation of gases into our atmosphere is a growing global concern that requires considerable quantification of the emission rates to mitigate the accumulation of gases in the atmosphere, especially the greenhouse gases (GHGs). In agriculture there are many sources of GHGs that require attention in order to develop practical mitigation strategies. Measuring these GHG sources often relies on highly technical instrumentation originally designed for applications outside of the emissions research in agriculture. Although the open-path laser (OPL) and open-path Fourier transform infrared (OP-FTIR) spectroscopic techniques are used in agricultural research currently, insight into their contributing error to emissions research has not been the focus of these studies. The objective of this study was to assess the applicability and performance (accuracy and precision) of OPL and OP-FTIR spectroscopic techniques for measuring gas mole fractions from agricultural sources. We measured the mole fractions of trace gases methane (CH 4), nitrous oxide (N 2 O), and ammonia (NH 3), downwind of point and area sources with a known release rate. The mole fractions measured by OP-FTIR and OPL were also input into models of atmospheric dispersion (WindTrax) allowing the calculation of fluxes. Trace gas release recoveries with WindTrax were examined by comparing the ratio of estimated and known fluxes. The OP-FTIR provided the best performance regarding stability of drift in stable conditions. The CH 4 OPL accurately detected the low background (free-air) level of CH 4 ; however, the NH 3 OPL was unable to detect the background values <10 ppbv. The dispersion modelling using WindTrax coupled with open-path measurements can be a useful tool to calculate trace gas fluxes from the well-defined source area. [ABSTRACT FROM AUTHOR]

Knowing one's HIV status is particularly important in the setting of recent tuberculosis (TB) exposure. Blood tests for assessment of tuberculosis infection, such as the QuantiFERON Gold in-tube test (QFT; Cellestis Limited, Carnegie, Victoria, Australia), offer the possibility of simultaneous screening for TB and HW with a single blood draw. We performed a cross-sectional analysis of all contacts to a highly infectious TB case in a large meatpacking factory. Twenty-two percent were foreign-born and 73% were black. Contacts were tested with both tuberculin skin testing (TST) and QFT. HIV testing was offered on an opt-out basis. Persons with TST [greater than or equal to] 10mm, positive QFT, and/or positive HIV test were offered latent TB treatment. Three hundred twenty-six contacts were screened: TST results were available for 266 people and an additional 24 reported a prior positive TST for a total of 290 persons with any TST result (89.0%). Adequate QFT specimens were obtained for 312 (95.7%) of persons. Thirty-two persons had QFT results but did not return for TST reading. Twenty-two percent met the criteria for latent TB infection. Eighty--eight percent accepted HIV testing. Two (0.7%) were HIV seropositive; both individuals were already aware of their HIV status, but one had stopped care a year previously. None of the HIV-seropositive persons had latent TB, but all were offered latent TB treatment per standard guidelines. This demonstrates that opt-out HIV testing combined with QFT in a large TB contact investigation was feasible and useful. HIV testing was also widely accepted. Pairing QFT with opt-out HIV testing should be strongly considered when possible. DOI: 10.1089/apc.2010.0102

It is widely accepted that atopic asthma depends on an allergic response in the airway, yet the immune mechanisms that underlie the development of airway hyperresponsiveness (AHR) are poorly understood. Mouse models of asthma have been developed to study the pathobiology of this disease, but there is considerable strain variation in the induction of allergic disease and AHR. The aim of this study was to compare the development of AHR in BALB/c, 129/Sv, and C57BL/6 mice after sensitization and challenge with ovalbumin (OVA). AHR to methacholine was measured using a modification of the forced oscillation technique in anesthetized, tracheostomized mice to distinguish between airway and parenchymal responses. Whereas all strains showed signs of allergic sensitization, BALB/c was the only strain to develop AHR, which was associated with the highest number of activated ([CD69.sup.+]) [CD4.sup.+] T cells in the airway wall and the highest levels of circulating OVA-specific [IgG.sub.1]. AHR did not correlate with total or antigen-specific IgE. We assessed the relative contribution of [CD4.sup.+] T cells and specific [IgG.sub.1] to the development of AHR in BALB/c mice using adoptive transfer of OVA-specific [CD4.sup.+] T cells from DO11.10 mice. AHR developed in these mice in a progressive fashion following multiple OVA challenges. There was no evidence that antigen-specific antibody had a synergistic effect in this model, and we concluded that the number of antigen-specific T cells activated and recruited to the airway wall was crucial for development of AHR. mouse models of asthma; forced oscillation technique; BALB/c; 129/Sv; C57BL/6

Understanding the mechanisms involved in respiratory tolerance to inhaled allergens could potentially result in improved therapies for asthma and allergic diseases. Airway hyperresponsiveness (AHR) is a major feature of allergic asthma, thus the aim of the current study was to investigate mechanisms underlying suppression of allergen-induced AHR during chronic allergen exposure. Adult BALB/c mice were systemically sensitized with ovalburain (OVA) in adjuvant and then challenged with a single 3 or 6 wk of OVA aerosols. Airway and parenchymal responses to inhaled methacholine (MCh), inflammatory cell counts, cytokines, OVA-specific IgE and Ig[G.sub.1], parenchymal histology, and numbers of airway [CD4.sup.+][69.sup.+] activated and [CD4.sup.+][25.sup.+][FoxP3.sup.+] regulatory T (Treg) cells were assessed 24 h after the final aerosol. Single OVA challenge resulted in AHR, eosinophilia, increased serum OVA-specific IgE, and T helper 2 (Th2) cytokines in bronchoalveolar lavage (BAL) but no difference in numbers of Treg compared with control mice. Three weeks of OVA challenges resulted in suppression of AHR and greater numbers of airway Treg cells and increased transforming growth factor-[[beta].sub.1] (TGF[[beta].sub.1]) compared with control mice despite the presence of increased eosinophilia, OVA-specific IgE and Ig[G.sub.1], and airway remodeling. Six weeks of OVA challenges restored AHR, whereas airway Treg numbers, TGF[[beta].sub.1], BAL eosinophilia, and Th2 cytokines returned to control levels. Partial in vivo depletion or adoptive transfer of Treg cells restored or inhibited AHR, respectively, but did not affect TGF[[beta].sub.1] or Th2 cytokine production. In conclusion, AHR suppression is mediated by airway Treg cells and potentially via a paracrine induction of TGF[[beta].sub.1] in the airways. asthma; T regulatory cell; lung function

Feather damaging behavior (feather picking) is a common malady of captive parrots. Diagnosis is challenging as a primary disadvantage to clinicians faced with diagnosis of parrot skin disease remains the lack of normative data for the healthy parrot epidermal microbiology. The objective of this pilot study was to establish bacterial and fungal cutaneous microbiota baselines for quaker parrots with and without feather loss. Healthy quaker parrots (Myiopsitta monachus n = 12) with intact feathers were compared to 12 quaker parrots with evidence of feather loss via next-generation DNA sequencing of bacteria and fungus swabbed from skin. Of 351 bacterial and 97 fungal species identified, no statistical differences occurred in bacteria or fungal alpha-diversity or beta-diversity based on age, sex, or feather loss. However, enclosure affected bacterial beta-diversity. The most abundant bacterial species for fully feathered quaker parrots were Exiguobacterium indicum, Sphingomonas yabuuchiae , and Corynebacterium spp.,. Fragaria/Populus euphratica, S. yabuuchiae, and E. indicum for quaker parrots with feather loss. Lactobacillales, Acinetobacter, Kocuria sp., and Streptococcus epidermidis were significantly enriched in fully feathered quaker parrots, while Streptococcaceae, Methylobacterium, Clostridiales, Nocardioidaceae, Nesterenkonia, and Actinomycetospora were significantly enriched in quaker parrots with feather loss. Both groups had Cladosporium halotolerans/sphaerospermum as the predominant fungus, while Capnodiales was significantly enriched in quaker parrots with feather loss. Use of next generation microbial sequencing as a preliminary diagnostic tool of bacterial and fungal communities of captive birds allows veterinarians to confirm cytologic diagnoses and circumvent the limitations of culture testing. Diagnostic implications include the potential transmission of pathogenic bacteria and/or fungi and pathogen resistance between cohoused birds. [ABSTRACT FROM AUTHOR]

The accumulation of gases into our atmosphere is a growing global concern that requires considerable quantification of the emission rates and mitigate the accumulation of gases in the atmosphere, especially the greenhouse gases (GHG). In agriculture there are many sources of GHG that require attention in order to develop practical mitigation strategies. Measuring these GHG sources often rely on highly technical instrumentation originally designed for applications outside of the emissions research in agriculture. Although the open-path laser (OPL) and open-path Fourier transform infrared (OP-FTIR) spectroscopic techniques are used in agricultural research currently, insight into their contributing error to emissions research has not been the focus of these studies. The objective of this study was to assess the applicability and performance (accuracy and precision) of OPL and OP-FTIR spectroscopic techniques for measuring gas concentration from agricultural sources. We measured the mixing ratios of trace gases methane (CH4), nitrous oxide (N2O), and ammonia (NH3), downwind of point and area sources with known release rates. The OP-FTIR provided the best performance regarding stability of drift in stable conditions. The CH4 OPL accurately detected the low background (free-air) level of CH4; however, the NH3 OPL was unable to detect the background values < 10 ppbv. [ABSTRACT FROM AUTHOR]

A reaction of a serine-derived organozinc reagent in benzene/dimethylacetamide with tetrahydrofuran solution of CuCN.2LiCl results in the formation of a zinc/copper reagent. The resulting compound reacts with allylic halides and tosylates to form enantiomerically pure substitution products in 32-65% yield through S(sub N)2' displacement of the leaving group. Reactions of the zinc/copper reagent with various electrophiles are discussed.

Abstract Background To characterise the acute physiological and inflammatory changes induced by low-dose RSV infection in mice. Methods BALB/c mice were infected as adults (8 wk) or weanlings (3 wk) with 1 × 105 pfu of RSV A2 or vehicle (intranasal, 30 μl). Inflammation, cytokines and inflammatory markers in bronchoalveolar lavage fluid (BALF) and airway and tissue responses to inhaled methacholine (MCh; 0.001 – 30 mg/ml) were measured 5, 7, 10 and 21 days post infection. Responsiveness to iv MCh (6 – 96 μg/min/kg) in vivo and to electrical field stimulation (EFS) and MCh in vitro were measured at 7 d. Epithelial permeability was measured by Evans Blue dye leakage into BALF at 7 d. Respiratory mechanics were measured using low frequency forced oscillation in tracheostomised and ventilated (450 bpm, flexiVent) mice. Low frequency impedance spectra were calculated (0.5 – 20 Hz) and a model, consisting of an airway compartment [airway resistance (Raw) and inertance (Iaw)] and a constant-phase tissue compartment [coefficients of tissue damping (G) and elastance (H)] was fitted to the data. Results Inflammation in adult mouse BALF peaked at 7 d (RSV 15.6 (4.7 SE) vs. control 3.7 (0.7) × 104 cells/ml; p < 0.001), resolving by 21 d, with no increase in weanlings at any timepoint. RSV-infected mice were hyperresponsive to aerosolised MCh at 5 and 7 d (PC200 Raw adults: RSV 0.02 (0.005) vs. control 1.1 (0.41) mg/ml; p = 0.003) (PC200 Raw weanlings: RSV 0.19 (0.12) vs. control 10.2 (6.0) mg/ml MCh; p = 0.001). Increased responsiveness to aerosolised MCh was matched by elevated levels of cysLT at 5 d and elevated VEGF and PGE2 at 7 d in BALF from both adult and weanling mice. Responsiveness was not increased in response to iv MCh in vivo or EFS or MCh challenge in vitro. Increased epithelial permeability was not detected at 7 d. Conclusion Infection with 1 × 105 pfu RSV induced extreme hyperresponsiveness to aerosolised MCh during the acute phase of infection in adult and weanling mice. The route-specificity of hyperresponsiveness suggests that epithelial mechanisms were important in determining the physiological effects. Inflammatory changes were dissociated from physiological changes, particularly in weanling mice.

Abstract Background Considerable variation exists in the protocols used to induce hyperresponsiveness in murine models of allergic sensitisation. We examined the effect of varying the number of antigen exposures at challenge on the development of methacholine responsiveness in systemically sensitised mice. Methods BALB/c mice were sensitised with ovalbumin (OVA), challenged with 1, 3 or 6 OVA aerosols. Lung function was measured using low frequency forced oscillations and partitioned into components representing the airways (Raw) and lung parenchyma (tissue damping (G) and tissue elastance (H)). Responsiveness to inhaled methacholine (MCh), inflammatory cell profile and circulating IgE were assessed 24 and 48 hours after challenge. The threshold dose of MCh required to elicit a detectable response (sensitivity) and response to 30 mg.mL-1 (maximal response) were determined for each compartment. Results Sensitivity; All three OVA protocols resulted in an increased sensitivity to MCh in Raw but not in G or H. These responses where present at 24 and 48 hrs, except 1 OVA aerosol in which changes had resolved by 48 hrs. Maximal response; 1 OVA aerosol increased maximal responses in Raw, G and H at 24 hrs, which was gone by 48 hrs. Three OVA aerosols increased responses in H at 48 hrs only. Six OVA challenges caused increases in Raw, G and H at both 24 and 48 hrs. Eosinophils increased with increasing antigen challenges. IgE was elevated by OVA sensitisation but not boosted by OVA aerosol challenge. Conclusions The pattern of eosinophilia, IgE and MCh responsiveness in mice was determined by antigen dose at challenge. In this study, increased sensitivity to MCh was confined to the airways whereas increases in maximal responses occurred in both the airway and parenchymal compartments. The presence of eosinophilia and IgE did not always coincide with increased responsiveness to inhaled MCh. These findings require further systematic study to determine whether different mechanisms underlie airway and parenchymal hyperresponsiveness post antigen challenge.

Neurogenic orthostatic hypotension (nOH) is a sustained reduction in blood pressure (BP) upon standing that is caused by autonomic dysfunction and is common among patients with a variety of neurodegenerative disorders (eg, Parkinson's disease, multiple system atrophy, pure autonomic failure). A systolic BP drop of ≥20 mmHg (or ≥10 mmHg diastolic) upon standing with little or no compensatory increase in heart rate is consistent with nOH. Symptoms of nOH include light-headedness, dizziness, presyncope, and syncope; these symptoms can severely impact patients' activities of daily living and increase the likelihood of potentially dangerous falls. Because of their patient contact, nurses and nurse practitioners can play a key role in identifying and evaluating patients at risk for nOH. It is advisable to screen for nOH in patients presenting with one or more of the following characteristics: those who have disorders associated with autonomic failure, those with episodes of falls or syncope, those with symptoms upon standing, those who are elderly or frail, or those taking multiple medications. Initial evaluations should include questions about postural symptoms and measurement of orthostatic BP and heart rate. A review of medications for potential agents that can have hypotensive effects should be performed before initiating treatment. Treatment for nOH may include non-pharmacologic measures and pharmacologic therapy. Droxidopa and midodrine are approved by the US Food and Drug Administration for the treatment of symptomatic nOH and symptomatic OH, respectively. nOH is associated with the coexistence of supine hypertension, and the two disorders must be carefully managed. In conclusion, timely screening and diagnosis of patients with nOH can streamline the path to disease management and treatment, potentially improving patient outcomes. [ABSTRACT FROM AUTHOR]

Current inactivated influenza vaccines are strain-specific and poorly effective against variant or mismatched viruses. They are standardized based on their hemagglutinin (HA) or ability to induce strain-specific hemagglutination inhibition (HAI) antibodies. The HA is known to undergo major conformational changes when exposed to the low pH environment of endosomes (pH 5.0 and 37°C), which are required for membrane fusion during virus cell entry. In an effort to improve these vaccines, influenza antigens treated under various low pH conditions were evaluated for increased cross-reactive antibody response and cross protection. It was found that a full range of structural and antigenic changes in HA could be induced by varying low pH treatment conditions from the mild (low pH at ≤25°C) to the strong (low pH at ≥37°C) as determined by analysis of potency, HA morphology, protease sensitivity, and reactivity with an anti-HA2 domain (CD) antibody. Inactivated antigens of both H1N1 and H3N2 strains treated at mild low pH conditions (0–25°C) exhibited only moderate HA structural and antigenic changes and markedly increased antibody response against HA2, the highly conserved part of HA, and cross protection against heterologous challenge in mice by up to 30% in survival. By contrast, antigen treated with low pH at 37°C showed more extensive structural and antigenic changes, and induced much less of an increase in antibody response against HA2, but a greater increase with response against HA1, and did not provide any increased cross protection. These results suggest that the increased response against HA2 obtained with the mild low pH treatment is associated with the increased cross protection. These antigens treated at the mild low pH conditions remained capable of inducing a high level of strain-specific HAI antibodies. Thus, they could readily be formulated as an inactivated influenza vaccine which not only provides the same strain-specific protection but also an increased cross protection against heterologous viruses. Such a vaccine could be particularly beneficial in cases of vaccine mismatch. [ABSTRACT FROM AUTHOR]

The article presents case study of a 71-year-old White male patient with autonomic imbalance and is dependent on nurses and caregivers for meals, medications, and assistance with basic care. It was observed that he had been resisting all attempts at standing and sitting and had been nonverbal for the entire duration of care.

Background: Accumulation mode particles (AMP) are formed from engine combustion and make up the inhalable vapour cloud of ambient particulate matter pollution. Their small size facilitates dispersal and subsequent exposure far from their original source, as well as the ability to penetrate alveolar spaces and capillary walls of the lung when inhaled. A significant immuno-stimulatory component of AMP is lipopolysaccharide (LPS), a product of Gram negative bacteria breakdown. As LPS is implicated in the onset and exacerbation of asthma, the presence or absence of LPS in ambient particulate matter (PM) may explain the onset of asthmatic exacerbations to PM exposure. This study aimed to delineate the effects of LPS and AMP on airway inflammation, and potential contribution to airways disease by measuring airway inflammatory responses induced via activation of the LPS cellular receptor, Toll-like receptor 4 (TLR-4).Methods: The effects of nebulized AMP, LPS and AMP administered with LPS on lung function, cellular inflammatory infiltrate and cytokine responses were compared between wildtype mice and mice not expressing TLR-4.Results: The presence of LPS administered with AMP appeared to drive elevated airway resistance and sensitivity via TLR-4. Augmented TLR4 driven eosinophilia and greater TNF-α responses observed in AMP-LPS treated mice independent of TLR-4 expression, suggests activation of allergic responses by TLR4 and non-TLR4 pathways larger than those induced by LPS administered alone. Treatment with AMP induced macrophage recruitment independent of TLR-4 expression.Conclusions: These findings suggest AMP-LPS as a stronger stimulus for allergic inflammation in the airways then LPS alone. [ABSTRACT FROM AUTHOR]

The severity of allergic diseases may be modified by vitamin D. However, the immune pathways modulated by the active form of vitamin D, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], are yet to be fully elucidated. In this study, naturally occurring CD4+ CD25+ cells from the skin-draining lymph nodes (SDLN) of mice treated with topical 1,25(OH)2D3 had an increased ability to suppress T helper type 2 (Th2) -skewed immune responses. CD4+ CD25+ cells transferred from mice treated with topical 1,25(OH)2D3 into ovalbumin (OVA) -sensitized mice challenged intranasally with OVA 18 hr later, significantly suppressed the capacity of airway-draining lymph node (ADLN) cells to proliferate and secrete cytokines in response to further OVA stimulation ex vivo. The CD4+ CD25+ cells from 1,25(OH)2D3-treated mice also reduced airway hyperresponsiveness and the proportions of neutrophils and eosinophils in bronchoalveolar lavage fluid (BALF). To test the effect of 1,25(OH)2D3 on cells able to respond to a specific antigen, CD4+ CD25+ cells were purified from the SDLN of OVA-T-cell receptor (TCR) transgenic mice treated 4 days earlier with topical 1,25(OH)2D3. CD4+ CD25+ cells from OVA-TCR mice treated with 1,25(OH)2D3 were able to alter BALF cell content and suppress ADLN responses to a similar degree to those cells from non-transgenic mice, suggesting that the effect of 1,25(OH)2D3 was not related to TCR signalling. In summary, topical 1,25(OH)2D3 increased the regulatory capacity of CD4+ CD25+ cells from the SDLN to suppress Th2-mediated allergic airway disease. This work highlights how local 1,25(OH)2D3 production by lung epithelial cells may modulate the suppressive activity of local regulatory T cells. [ABSTRACT FROM AUTHOR]

The double sigmoidal nature of the mouse pressure-volume (PV) curve is well recognized but largely ignored. This study systematically examined the effect of inflating the mouse lung to 40 cm H2O transrespiratory pressure (Prs) in vivo. Adult BALB/c mice were anesthetized, tracheostomized, and mechanically ventilated. Thoracic gas volume was calculated using plethysmography and electrical stimulation of the intercostal muscles. Lung mechanics were tracked during inflation-deflation maneuvers using a modification of the forced oscillation technique. Inflation beyond 20 cm H2O caused a shift in subsequent PV curves with an increase in slope of the inflation limb and an increase in lung volume at 20 cm H2O. There was an overall decrease in tissue elastance and a fundamental change in its volume dependence. This apparent "softening" of the lung could be recovered by partial degassing of the lung or applying a negative transrespiratory pressure such that lung volume decreased below functional residual capacity. Allowing the lung to spontaneously recover revealed that the lung required ∼1 h of mechanical ventilation to return to the original state. We propose a number of possible mechanisms for these observations and suggest that they are most likely explained by the unfolding of alveolar septa and the subsequent redistribution of the fluid lining the alveoli at high transrespiratory pressure. [ABSTRACT FROM AUTHOR]

Many chronic human lung diseases have their origin in early childhood, yet most murine models used to study them utilize adult mice. An important component of the asthma phenotype is exaggerated airway responses, frequently modelled by methacholine (MCh) challenge. The present study was undertaken to characterize MCh responses in mice from 2 to 8 wk of age measuring absolute lung volume and volume-corrected respiratory mechanics as outcome variables. Female BALB/c mice aged 2, 3, 4, 6, and 8 wk were studied during cumulative intravenous MCh challenge. Following each MCh dose, absolute lung volume was measured plethysmographically at functional residual volume and during a slow inflation to 20-hPa transrespiratory pressure. Respiratory system impedance was measured continuously during the inflation maneuver and partitioned into airway and constant-phase parenchymal components by model fitting. Volume-corrected (specific) estimates of respiratory mechanics were calculated. Intravenous MCh challenge induced a predominantly airway response with no evidence of airway closure in any age group. No changes in functional residual volume were seen in mice of any age during the MCh challenge. The specific airway resistance MCh dose response curves did not show significant differences between the age groups. The results from the present study do not show systematic differences in MCh responsiveness in mice from 2 to 8 wk of age. [ABSTRACT FROM AUTHOR]

Most studies using mice to model human lung diseases are carried out in adults, although there is emerging interest in the effects of allergen, bacterial, and viral exposure early in life. This study aims to characterize lung function in BALB/c mice from infancy (2 wk) through to adulthood (8 wk). The low-frequency forced oscillation technique was used to obtain impedance data, partitioned into components representing airway resistance, tissue damping, tissue elastance, and hysteresivity (tissue damping/ tissue elastance). Measurements were made at end-expiratory pause (transrespiratory system pressure = 2 cmH2O) and during relaxed slow expiration from 20 to 0 cmH2O. Airway resistance decreased with age from 0.63 cmH2O·ml-1·s at 2 wk to 0.24 cmH2O·ml -1·s at 8 wk (P < 0.001). Both tissue damping and tissue elastance decreased with age (P < 0.001) from 2 to 5 wk, then plateaued through to 8 wk (P < 0.001). This pattern was seen both in measurements taken at end-expiratory pause and during expiration. There were no age-related changes seen in hysteresivity when measured at end-expiratory pause, but the pattern of volume dependence did differ with the age of the mice. These changes in respiratory mechanics parallel the reported structural changes of the murine lung from the postnatal period into adulthood. [ABSTRACT FROM AUTHOR]

Background: To characterise the acute physiological and inflammatory changes induced by low-dose RSV infection in mice. Methods: BALB/c mice were infected as adults (8 wk) or weanlings (3 wk) with 1 x 105 pfu of RSV A2 or vehicle (intranasal, 30 μl). Inflammation, cytokines and inflammatory markers in bronchoalveolar lavage fluid (BALF) and airway and tissue responses to inhaled methacholine (MCh; 0.001 - 30 mg/ml) were measured 5, 7, 10 and 21 days post infection. Responsiveness to iv MCh (6 - 96 μg/min/kg) in vivo and to electrical field stimulation (EFS) and MCh in vitro were measured at 7 d. Epithelial permeability was measured by Evans Blue dye leakage into BALF at 7 d. Respiratory mechanics were measured using low frequency forced oscillation in tracheostomised and ventilated (450 bpm, flexiVent) mice. Low frequency impedance spectra were calculated (0.5 - 20 Hz) and a model, consisting of an airway compartment [airway resistance (Raw) and inertance (Iaw)] and a constant-phase tissue compartment [coefficients of tissue damping (G) and elastance (H)] was fitted to the data. Results: Inflammation in adult mouse BALF peaked at 7 d (RSV 15.6 (4.7 SE) vs. control 3.7 (0.7) x 104 cells/ml; p < 0.001), resolving by 21 d, with no increase in weanlings at any timepoint. RSV-infected mice were hyperresponsive to aerosolised MCh at 5 and 7 d (PC200 Raw adults: RSV 0.02 (0.005) vs. control 1.1 (0.41) mg/ml; p = 0.003) (PC200 Raw weanlings: RSV 0.19 (0.12) vs. control 10.2 (6.0) mg/ml MCh; p = 0.001). Increased responsiveness to aerosolised MCh was matched by elevated levels of cysLT at 5 d and elevated VEGF and PGE2 at 7 d in BALF from both adult and weanling mice. Responsiveness was not increased in response to iv MCh in vivo or EFS or MCh challenge in vitro. Increased epithelial permeability was not detected at 7 d. Conclusion: Infection with 1 x 105 pfu RSV induced extreme hyperresponsiveness to aerosolised MCh during the acute phase of infection in adult and weanling mice. The route-specificity of hyperresponsiveness suggests that epithelial mechanisms were important in determining the physiological effects. Inflammatory changes were dissociated from physiological changes, particularly in weanling mice. [ABSTRACT FROM AUTHOR]

Background: Considerable variation exists in the protocols used to induce hyperresponsiveness in murine models of allergic sensitisation. We examined the effect of varying the number of antigen exposures at challenge on the development of methacholine responsiveness in systemically sensitised mice. Methods: BALB/c mice were sensitised with ovalbumin (OVA), challenged with 1, 3 or 6 OVA aerosols. Lung function was measured using low frequency forced oscillations and partitioned into components representing the airways (Raw) and lung parenchyma (tissue damping (G) and tissue elastance (H)). Responsiveness to inhaled methacholine (MCh), inflammatory cell profile and circulating IgE were assessed 24 and 48 hours after challenge. The threshold dose of MCh required to elicit a detectable response (sensitivity) and response to 30 mg.mL-1 (maximal response) were determined for each compartment. Results: Sensitivity; All three OVA protocols resulted in an increased sensitivity to MCh in Raw but not in G or H. These responses where present at 24 and 48 hrs, except 1 OVA aerosol in which changes had resolved by 48 hrs. Maximal response; 1 OVA aerosol increased maximal responses in Raw, G and H at 24 hrs, which was gone by 48 hrs. Three OVA aerosols increased responses in H at 48 hrs only. Six OVA challenges caused increases in Raw, G and H at both 24 and 48 hrs. Eosinophils increased with increasing antigen challenges. IgE was elevated by OVA sensitisation but not boosted by OVA aerosol challenge. Conclusions: The pattern of eosinophilia, IgE and MCh responsiveness in mice was determined by antigen dose at challenge. In this study, increased sensitivity to MCh was confined to the airways whereas increases in maximal responses occurred in both the airway and parenchymal compartments. The presence of eosinophilia and IgE did not always coincide with increased responsiveness to inhaled MCh. These findings require further systematic study to determine whether different mechanisms underlie airway and parenchymal hyperresponsiveness post antigen challenge. [ABSTRACT FROM AUTHOR]

Reports on the development of a tracking impedance estimation technique to follow the changes in total respiratory impedance (Zrs) during slow total lung capacity maneuvers in six anesthetized and mechanically ventilated BALB/c mice; Findings indicating that single-frequency resistance values may become inappropriate as surrogates of airway resistance (Raw) when tissue impedance is changing.

Studies the volume dependence of airway and tissue impedances in mice. Use of model fitting to obtain parameters for airway and tissue mechanics; Pattern of changes in respiratory mechanics with increasing lung volume; Progressive fall in airway resistance; Increase in coefficients of tissue damping and elastance.