Metabolic, hygric and ventilatory physiology of a hypermetabolic marsupial, the honey possum (Tarsipes rostratus)

The honey possum is the only non-volant mammal to feed exclusively on a diet of nectar and pollen. Like other mammalian and avian nectarivores, previous studies indicated that the honey possum's basal metabolic rate was higher than predicted for a marsupial of equivalent body mass. However, these early measurements have been questioned. We re-examined the basal metabolic rate (2.52 +/- A 0.222 ml O(2) g(-1) h(-1)) of the honey possum and confirm that it is indeed higher (162%) than predicted for other marsupials both before and after accounting for phylogenetic history. This, together with its small body mass (5.4 +/- A 0.14 g; 1.3% of that predicted by phylogeny) may be attributed to its nectarivorous diet and mesic distribution. Its high-basal metabolic rate is associated with a high-standard body temperature (36.6 +/- A 0.48A degrees C) and oxygen extraction (19.4%), but interestingly the honey possum has a high point of relative water economy (17.0A degrees C) and its standard evaporative water loss (4.33 +/- A 0.394 mg H(2)O g(-1) h(-1)) is not elevated above that of other marsupials, despite its mesic habitat and high dietary water intake.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Previous influenza infection exacerbates allergen specific response and impairs airway barrier integrity in pre‐sensitized mice

In this study we assessed the effects of antigen exposure in mice pre-sensitized with allergen following viral infection on changes in lung function, cellular responses and tight junction expression. Female BALB/c mice were sensitized to ovalbumin and infected with influenza A before receiving a second ovalbumin sensitization and challenge with saline, ovalbumin (OVA) or house dust mite (HDM). Fifteen days post-infection, bronchoalveolar inflammation, serum antibodies, responsiveness to methacholine and barrier integrity were assessed. There was no effect of infection alone on bronchoalveolar lavage cellular inflammation 15 days post-infection; however, OVA or HDM challenge resulted in increased bronchoalveolar inflammation dominated by eosinophils/neutrophils or neutrophils, respectively. Previously infected mice had higher serum OVA-specific IgE compared with uninfected mice. Mice previously infected, sensitized and challenged with OVA were most responsive to methacholine with respect to airway resistance, while HDM challenge caused significant increases in both tissue damping and tissue elastance regardless of previous infection status. Previous influenza infection was associated with decreased claudin-1 expression in all groups and decreased occludin expression in OVA or HDM-challenged mice. This study demonstrates the importance of the respiratory epithelium in pre-sensitized individuals, where influenza-infection-induced barrier disruption resulted in increased systemic OVA sensitization and downstream effects on lung function

Maternal high fat diet compromises survival and modulates lung development of offspring, and impairs lung function of dams (female mice)

© 2019 The Author(s). Published in Respiratory Research. Background: Epidemiological studies have identified strong relationships between maternal obesity and offspring respiratory dysfunction; however, the causal direction is not known. We tested whether maternal obesity alters respiratory function of offspring in early life. Methods: Female C57Bl/6 J mice were fed a high or low fat diet prior to and during two rounds of mating and resulting pregnancies with offspring lung function assessed at 2 weeks of age. The lung function of dams was measured at 33 weeks of age. Results: A high fat diet caused significant weight gain prior to conception with dams exhibiting elevated fasting glucose, and glucose intolerance. The number of surviving litters was significantly less for dams fed a high fat diet, and surviving offspring weighed more, were longer and had larger lung volumes than those born to dams fed a low fat diet. The larger lung volumes significantly correlated in a linear fashion with body length. Pups born from the second pregnancy had reduced tissue elastance compared to pups born from the first pregnancy, regardless of the dam's diet. As there was reduced offspring survival born to dams fed a high fat diet, the statistical power of lung function measures of offspring was limited. There were signs of increased inflammation in the bronchoalveolar lavage fluid of dams (but not offspring) fed a high fat diet, with more tumour necrosis factor-α, interleukin(IL)-5, IL-33 and leptin detected. Dams that were fed a high fat diet and became pregnant twice had reduced fasting glucose immediately prior to the second mating, and lower levels of IL-33 and leptin in bronchoalveolar lavage fluid. Conclusions: While maternal high fat diet compromised litter survival, it also promoted somatic and lung growth (increased lung volume) in the offspring. Further studies are required to examine downstream effects of this enhanced lung volume on respiratory function in disease settings

Elevated 17β-Estradiol Protects Females from Influenza A Virus Pathogenesis by Suppressing Inflammatory Responses

Studies of the 1918 H1N1 influenza pandemic, the H5N1 avian influenza outbreak, and the 2009 H1N1 pandemic illustrate that sex and pregnancy contribute to severe outcome from infection, suggesting a role for sex steroids. To test the hypothesis that the sexes respond differently to influenza, the pathogenesis of influenza A virus infection was investigated in adult male and female C57BL/6 mice. Influenza infection reduced reproductive function in females and resulted in greater body mass loss, hypothermia, and mortality in females than males. Whereas lung virus titers were similar between the sexes, females had higher induction of proinflammatory cytokines and chemokines, including TNF-α, IFN-γ, IL-6, and CCL2, in their lungs than males. Removal of the gonads in both sexes eliminated the sex difference in influenza pathogenesis. Manipulation of testosterone or dihydrotestosterone concentrations in males did not significantly impact virus pathogenesis. Conversely, females administered high doses of estradiol had a ≥10-fold lower induction of TNF-α and CCL2 in the lungs and increased rates of survival as compared with females that had either low or no estradiol. The protective effects of estradiol on proinflammatory cytokines and chemokines, morbidity, and mortality were primarily mediated by signaling through estrogen receptor α (ERα). In summary, females suffer a worse outcome from influenza A virus infection than males, which can be reversed by administration of high doses of estradiol to females and reflects differences in the induction of proinflammatory responses and not in virus load

Comparative physiology of Australian quolls (Dasyurus; Marsupialia)

Quolls (Dasyurus) are medium-sized carnivorous dasyurid marsupials. Tiger (3,840 g) and eastern quolls (780 g) are mesic zone species, northern quolls (516 g) are tropical zone, and chuditch (1,385 g) were once widespread through the Australian arid zone. We found that standard physiological variables of these quolls are consistent with allometric expectations for marsupials. Nevertheless, inter-specific patterns amongst the quolls are consistent with their different environments. The lower T ^sub b^ of northern quolls (34°C) may provide scope for adaptive hyperthermia in the tropics, and they use torpor for energy/water conservation, whereas the larger mesic species (eastern and tiger quolls) do not appear to. Thermolability varied from little in eastern (0.035°C °C^sup -1^) and tiger quolls (0.051°C ºC^sup -1^) to substantial in northern quolls (0.100°C ºC^sup -1^) and chuditch (0.146°C ºC^sup -1^), reflecting body mass and environment. Basal metabolic rate was higher for eastern quolls (0.662 ± 0.033 ml O^sub 2^ g^sup -1^ h^sup -1^), presumably reflecting their naturally cool environment. Respiratory ventilation closely matched metabolic demand, except at high ambient temperatures where quolls hyperventilated to facilitate evaporative heat loss; tiger and eastern quolls also salivated. A higher evaporative water loss for eastern quolls (1.43 ± 0.212 mg H^sub 2^O g^sup -1^ h^sup -1^) presumably reflects their more mesic distribution. The point of relative water economy was low for tiger (-1.3°C), eastern (-12.5°C) and northern (+3.3) quolls, and highest for the chuditch (+22.6°C). We suggest that these differences in water economy reflect lower expired air temperatures and hence lower respiratory evaporative water loss for the arid-zone chuditch relative to tropical and mesic quolls

Mechanical Abnormalities of the Airway Wall in Adult Mice After Intrauterine Growth Restriction

© Copyright © 2019 Noble, Kowlessur, Larcombe, Donovan and Wang. Developmental abnormalities of airways may impact susceptibility to asthma in later life. We used a maternal hypoxia-induced mouse model of intrauterine growth restriction (IUGR) to examine changes in mechanical properties of the airway wall. Pregnant BALB/c mice were housed under hypoxic conditions (10.5% O2) from gestational day (GD) 11 to GD 17.5 (IUGR; term, GD 21). Following hypoxic exposure, mice were returned to a normoxic environment (21% O2). A control group of pregnant mice were housed under normoxic conditions throughout pregnancy. At 8 weeks postnatal age, offspring were euthanized and a tracheasectomy performed. Tracheal segments were studied in organ baths to measure active airway smooth muscle (ASM) stress to carbachol and assess passive mechanical properties (stiffness) from stress-strain curves. In a separate group of anesthetized offspring, the forced oscillation technique was used to examine airway mechanics from relative changes in airway conductance during slow inflation and deflation between 0 and 20 cmH2O transrespiratory pressure. From predicted radius-pressure loops, storage and loss moduli and hysteresivity were calculated. IUGR offspring were lighter at birth (p < 0.05) and remained lighter at 8 weeks of age (p < 0.05) compared with Controls. Maximal stress was reduced in male IUGR offspring compared with Controls (p < 0.05), but not in females. Sensitivity to contractile agonist was not affected by IUGR or sex. Compared with the Control group, airways from IUGR animals were stiffer in vitro (p < 0.05). In vivo, airway hysteresivity (p < 0.05) was increased in the IUGR group, but there was no difference in storage or loss moduli between groups. In summary, the effects of IUGR persist to the mature airway wall, where there are clear abnormalities to ASM contractile properties and passive wall mechanics. We propose that mechanical abnormalities of the airway wall acquired through disrupted fetal growth impact susceptibility to disease

Rhinovirus exacerbates house-dust-mite induced lung disease in adult mice

Human rhinovirus is a key viral trigger for asthma exacerbations. To date, murine studies investigating rhinovirus-induced exacerbation of allergic airways disease have employed systemic sensitisation/intranasal challenge with ovalbumin. In this study, we combined human-rhinovirus infection with a clinically relevant mouse model of aero-allergen exposure using house-dust-mite in an attempt to more accurately understand the links between human-rhinovirus infection and exacerbations of asthma. Adult BALB/c mice were intranasally exposed to low-dose house-dust-mite (or vehicle) daily for 10 days. On day 9, mice were inoculated with human-rhinovirus-1B (or UV-inactivated human-rhinovirus-1B). Forty-eight hours after inoculation, we assessed bronchoalveolar cellular inflammation, levels of relevant cytokines/serum antibodies, lung function and responsiveness/sensitivity to methacholine. House-dust-mite exposure did not result in a classical TH 2 -driven response, but was more representative of noneosinophilic asthma. However, there were significant effects of house-dustmite exposure on most of the parameters measured including increased cellular inflammation (primarily macrophages and neutrophils), increased total IgE and house-dust-mite-specific IgG 1 and increased responsiveness/sensitivity to methacholine. There were limited effects of human-rhinovirus-1B infection alone, and the combination of the two insults resulted in additive increases in neutrophil levels and lung parenchymal responses to methacholine (tissue elastance). We conclude that acute rhinovirus infection exacerbates house-dust-mite-induced lung disease in adult mice. The similarity of our results using the naturally occurring allergen house-dust-mite, to previous studies using ovalbumin, suggests that the exacerbation of allergic airways disease by rhinovirus infection could act via multiple or conserved mechanisms. © 2014 Phan et al