Allergic asthma is characterized by airway inflammation initiated by adaptive immune responses to aeroallergens. Recent data suggest that severe asthma may be a different form of asthma rather than an increase in asthma symptoms and that innate immune responses to LPS can modulate adaptive immune responses to allergens. In this study, we evaluated the hypothesis that airway exposure to different doses of LPS induces different form of asthma. Our study showed that neutrophilic inflammation and IFN-γ expression were higher in induced sputum from severe asthma patients than from mild to moderate asthmatics. Animal experiments indicated that allergen sensitization with low-dose LPS (0.1 μg) induced type 2 asthma phenotypes, i.e., airway hyperresponsiveness, eosinophilic inflammation, and allergen-specific IgE up-regulation. In contrast, allergen sensitization with high-dose LPS (10 μg) induced asthma phenotypes, i.e., airway hyperresponsiveness and noneosinophilic inflammation that were not developed in IFN-γ-deficient mice, but unaffected in the absence of IL-4. During the allergen sensitization period, TNF-α expression was found to be enhanced by both low- and high-dose LPS, whereas IL-12 expression was only enhanced by high-dose LPS. Interestingly, the asthma phenotypes induced by low-dose LPS, but not by high-dose LPS, were completely inhibited in TNF-α receptor-deficient mice, whereas the asthma phenotypes induced by high-dose LPS were abolished in the homozygous null mutation of the STAT4 gene. These findings suggest that airway exposure levels of LPS induces different forms of asthma that are type 1 and type 2 asthma phenotypes by high and low LPS levels, respectively.
SUMMARY Impaired consciousness in temporal lobe seizures has a major negative impact on quality of life. The prevailing view holds that this disorder impairs consciousness by seizure spread to the bilateral temporal lobes. We propose instead that seizures invade subcortical regions and depress arousal, causing impairment through decreases rather than through increases in activity. Using functional magnetic resonance imaging in a rodent model, we found increased activity in regions known to depress cortical function including lateral septum and anterior hypothalamus. Importantly, we found suppression of intralaminar thalamic and brainstem arousal systems and suppression of the cortex. At a cellular level, we found reduced firing of identified cholinergic neurons in the brainstem pedunculopontine tegmental nucleus and basal forebrain. Finally, we used enzyme-based amperometry to demonstrate reduced cholinergic neurotransmission in both cortex and thalamus. Decreased subcortical arousal is a novel mechanism for loss of consciousness in focal temporal lobe seizures.
Nanowires can serve as three-dimensional platforms at the nanometer scale for highly efficient chemical energy storage and conversion vehicles, such as fuel cells and secondary batteries. Here we report a coin-type Si nanowire (NW) half-cell Li-ion battery showing the Li capacity of approximately 4000 mAh/g, which nearly approaches the theoretical limit of 4200 mAh/g, with very high Coulombic efficiency of up to 98%. Concomitantly, we provide direct evidence of reversible phase transitions in the Si NW anodes at the full electrochemical cycles, varying from pure Si to Li22Si5 phase, which has been known empirically inaccessible in the bulk limit.
ObjectiveTo prevent the occurrence of CV events such as MI and stroke among professional drivers in Korea, bus drivers were compared to other occupations through the Framingham risk scoring system (FRS) or metabolic syndrome (MS) of cardiovascular disease (CVD) risk assessment methods.MethodsIn October 2012, a health examination survey was conducted for 443 male bus drivers in a big city. Their CVD risk factors were compared to those of a ‘total employed’ (A group) and ‘crafts and machine operators’ (B group) extracted from Fifth Korea National Health and Nutrition Examination Survey (KNHANES, 2010) data by using FRS and MS. We calculated proportions of the CVD risk factors distribution between bus drivers and the A, B groups by the bootstrapping method. The Odds ratio (OR) between CV event risk combining MS with CHD equivalent risk of FRS and occupational factors like shift patterns and professional driving duration/age ratios (PDAR) of bus drivers was calculated through multinominal logistic regression.ResultsThe proportion of BMI ≥ 25 kg/m2 was 53.9% and waist circumference ≥ 90cm was 40.9% among bus drivers. Hypertension and MS prevalence of bus drivers was 53.3%, 49.9% which is higher than 17.6%, 22.6% in the A group and 19.7%, 23.8% in the B group respectively. OR of high CV event risk in alternate shift was 2.58 (95% CI 1.33~5.00) in comparison with double shift pattern and OR in PDAR ≥ 0.5 was 2.18 (95% CI 1.15~4.14).ConclusionMiddle aged male drivers in a big city of Korea stand a higher chance of developing CV event than other professions of the same age.
The role of alveolar macrophages (AMs) in the pathogenesis of asthma is still unknown. The aim of the present study was to investigate the effects of AM in the murine model of asthma. AMs were selectively depleted by liposomes containing clodronate just before allergen challenges, and changes in inflammatory cells and cytokine concentrations in bronchoalveolar lavage (BAL) fluid were measured. AMs were then adoptively transferred to AM-depleted sensitized mice and changes were measured. Phenotypic changes in AMs were evaluated after in vitro allergen stimulation. AM-depletion after sensitization significantly increased the number of eosinophils and lymphocytes and the concentrations of IL-4, IL-5 and GM-CSF in BAL fluid. These changes were significantly ameliorated only by adoptive transfer of unsensitized AMs, not by sensitized AMs. In addition, in vitro allergen stimulation of AMs resulted in their gaining the ability to produce inflammatory cytokines, such as IL-1β, IL-6 and TNF-α, and losing the ability to suppress GM-CSF concentrations in BAL fluid. These findings suggested that AMs worked probably through GM-CSF-dependent mechanisms, although further confirmatory experiments are needed. Our results indicate that the role of AMs in the context of airway inflammation should be re-examined.
Background and Purpose-To clarify the role of vascular NAD(P)H oxidase in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH), both the activity and/or activation mechanisms of NAD(P)H oxidase in the cerebral vasculature and the effect of oxidase inhibition on SAH-induced cerebral vasospasm were assessed. Methods-The changes in the luminal perimeter of the middle cerebral artery were measured histologically after SAH was induced according to a 2-hemorrhage model in rats. The NAD(P)H oxidase activity in the cerebral vasculature was measured with a lucigenin assay at different time intervals from 12 hours to 14 days after injection of autologous blood into cisterna magna. The membrane translocation of p47phox and the protein expression of membrane subunits (gp91phox and p22phox) of NAD(P)H oxidase were analyzed using Western blot analysis. Results-The luminal perimeter of the middle cerebral artery started to decrease on day 1 and peaked on day 5 after a second injection of blood, and these changes were significantly ameliorated by treatment with an NAD(P)H oxidase inhibitor, diphenyleneiodonium. At 24 hours after the second injection of blood, both vascular production of superoxide anion and NAD(P)H oxidase activity were markedly increased with enhanced membrane translocation of p47phox, but by 48 hours the enzyme activity had regained normal values. However, no significant changes in the expression of gp91phox and p22phox were observed throughout the experiments. Conclusions-These findings suggest that the activation of NAD(P)H oxidase through enhanced assembly of the oxidase components in the early stages of SAH might contribute to the delayed cerebral vasospasm in SAH rats.
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