Route of administration affects corticosteroid sensitivity of a combined ovalbumin and lipopolysaccharide model of asthma exacerbation in guinea-pigs

Lipopolysaccharide (LPS) contributes to asthma exacerbations and development of inhaled corticosteroid insensitivity. Complete resistance to systemic corticosteroids is rare and most patients lie on a continuum of steroid responsiveness. The objective of this study was to examine the sensitivity of combined ovalbumin- (Ova) and LPS-induced functional and inflammatory responses to inhaled and systemic corticosteroid in conscious guinea-pigs, to test the hypothesis that the route of administration affects its sensitivity. Guinea-pigs were sensitised to Ova and challenged with inhaled Ova alone or combined with LPS. Airways function was determined by measuring specific airways conductance via whole-body plethysmography. Airways hyperresponsiveness to histamine was determined pre- and 24h post-Ova challenge. Airways inflammation and underlying mechanisms were determined from bronchoalveolar lavage cell counts and lung tissue cytokines. Vehicle or dexamethasone was administered by once-daily intraperitoneal injection (5, 10 or 20 mg/kg) or twice-daily inhalation (4 or 20 mg/ml) for 6 days before Ova challenge or Ova with LPS. LPS exacerbated Ova-induced responses, elongating early asthmatic responses (EAR), prolonging bronchoconstriction by histamine and further elevating airways inflammation. Intraperitoneal dexamethasone (20 mg/kg) significantly reduced the elongated EAR and airways inflammation but not the increased bronchoconstriction to histamine. In contrast, inhaled dexamethasone (20 mg/ml), which inhibited responses to Ova alone, did not significantly reduce functional and inflammatory responses to combined Ova and LPS. Combined Ova and LPS-induced functional and inflammatory responses are insensitive to inhaled but only partially sensitive to systemic dexamethasone. These results suggest that the route of corticosteroid administration may be important in determining the sensitivity of asthmatic responses to these agents

Lipopolysaccharide exacerbates functional and inflammatory responses to ovalbumin and decreases sensitivity to inhaled fluticasone propionate in a guinea-pig model of asthma

Background and Purpose Asthma exacerbations contribute to corticosteroid insensitivity. Lipopolysaccharide (LPS) is ubiquitous in the environment. It causes bronchoconstriction and airways inflammation and may therefore exacerbate allergen responses. This study examined whether LPS and ovalbumin co-administration could exacerbate the airways inflammatory and functional responses to ovalbumin in conscious guinea-pigs and whether these exacerbated responses were insensitive to inhaled corticosteroid treatment with fluticasone propionate. Experimental Approach Guinea-pigs were sensitized and challenged with ovalbumin and airways function recorded as specific airways conductance (sGaw) by whole body plethysmography. Airways inflammation was measured from lung histology and bronchoalveolar lavage. Airways hyperreactivity (AHR) to inhaled histamine was examined 24h after ovalbumin. LPS was inhaled alone or 24 or 48 hours before ovalbumin and combined with ovalbumin. Fluticasone propionate (0.05, 0.1, 0.5 or 1mg/ml) or vehicle (ethanol:DMSO:saline 30:30:40) was nebulised for 15 minutes twice daily for 6 days before ovalbumin or LPS exposure. Key Results Ovalbumin inhalation caused early (EAR) and late asthmatic responses (LAR), airways hypereactivity to histamine and influx of inflammatory cells into the lungs. LPS 48 hours before and co-administered with ovalbumin exacerbated the response with increased length of the EAR, prolonged response to histamine and elevated inflammatory cells. FP 0.5 and 1mg/ml reduced the LAR, AHR and cell influx with ovalbumin alone, but was ineffective when guinea-pigs were exposed to LPS before and with ovalbumin. Conclusions and Implications LPS exposure exacerbates airways inflammatory and functional responses to allergen inhalation and decreases corticosteroid sensitivity. Its widespread presence in the environment could contribute to asthma exacerbations and corticosteroid insensitivity in humans

Adjustment of sensitisation and challenge protocols restores functional and inflammatory responses to ovalbumin in guinea-pigs

AbstractIntroductionInhalation of antigen in atopic asthma induces early (EAR) and late asthmatic responses (LARs), inflammatory cell infiltration and airways hyperresponsiveness (AHR). Previously, we have established a protocol of sensitisation and subsequent ovalbumin (Ova) inhalation challenge in guinea-pigs which induced these 4 features (Smith & Broadley, 2007). However, the responses of guinea-pigs to Ova challenge have recently declined, producing no LAR or AHR and diminished EAR and cells. By making cumulative modifications to the protocol, we sought to restore these features.MethodsGuinea-pigs were sensitised with Ova (i.p. 100 or 150μg) on days 1 and 5 or days 1, 4 and 7 and challenged with nebulised Ova (100 or 300μg/ml, 1h) on day 15. Airway function was measured in conscious guinea-pigs by whole-body plethysmography to record specific airway conductance (sGaw). Airway responsiveness to aerosolized histamine (0.3mM) was determined before and 24h after Ova challenge. Bronchoalveolar lavage was performed for total and differential inflammatory cell counts. Lung sections were stained for counting of eosinophils.ResultsLack of AHR and LAR with the original protocol was confirmed. Increasing the Ova challenge concentration from 100 to 300μg/ml restored AHR and eosinophils and increased the peak of the EAR. Increasing the number of sensitisation injections from 2 to 3 did not alter the responses. Increasing the Ova sensitisation concentration from 100 to 150μg significantly increased total cells, particularly eosinophils. A LAR was revealed and lymphocytes and eosinophils increased when either the Al(OH)3 concentration was increased or the duration between the final sensitisation injection and Ova challenge was extended from 15 to 21days.DiscussionThis study has shown that declining allergic responses to Ova in guinea-pigs could be restored by increasing the sensitisation and challenge conditions. It has also demonstrated an important dissociation between EAR, LAR, AHR and inflammation

Analysis of Relative Contributions and Challenges of Acquiring Information Literacy Skills for Lawmakers’ Constituency Performance in South West Nigeria

Abstract: This study examined the challenges of information literacy skills capacity building for the lawmakers in the South West Nigeria. Survey method was adopted for this using questionnaire as instrument for data collection. 177 legislators participated from the six states of assembly in South-West Nigeria through total enumeration to determine the number of lawmakers in the study. The questionnaire titled ``Lawmakers’ Information Literacy Skills and Constituency Performance in South-West Nigeria (LILSCP)” were distributed to responded, out of which 151 usable copies were returned to the researcher. The data collected were analyzed and presented in tables using descriptive statistics particularly frequency counts, standard deviation and simple percentages. The result of the study showed that 66.4% of the legislators have contributed to the development of their constituencies through a number of projects. 73% of the responded agreed they initiated and organized programmers based on their level of information literacy skills, as against those who search for information through CD-ROM for collaboration with international agencies find it difficult. 59% of the respondents could not locate most appropriate information resources, as against 3% who did not know how to locate at all. In spite of these challenges faced by the legislators, they were still able to contribute execute some developmental project. However, a well-informed lawmaker is a panacea for robust deliberations in the house; thus, adequate recommendations were made to achieve this

Analysis of Relative Contributions and Challenges of Acquiring Information Literacy Skills for Lawmakers’ Constituency Performance in South West Nigeria

Abstract: This study examined the challenges of information literacy skills capacity building for the lawmakers in the South West Nigeria. Survey method was adopted for this using questionnaire as instrument for data collection. 177 legislators participated from the six states of assembly in South-West Nigeria through total enumeration to determine the number of lawmakers in the study. The questionnaire titled ``Lawmakers’ Information Literacy Skills and Constituency Performance in South-West Nigeria (LILSCP)” were distributed to responded, out of which 151 usable copies were returned to the researcher. The data collected were analyzed and presented in tables using descriptive statistics particularly frequency counts, standard deviation and simple percentages. The result of the study showed that 66.4% of the legislators have contributed to the development of their constituencies through a number of projects. 73% of the responded agreed they initiated and organized programmers based on their level of information literacy skills, as against those who search for information through CD-ROM for collaboration with international agencies find it difficult. 59% of the respondents could not locate most appropriate information resources, as against 3% who did not know how to locate at all. In spite of these challenges faced by the legislators, they were still able to contribute execute some developmental project. However, a well-informed lawmaker is a panacea for robust deliberations in the house; thus, adequate recommendations were made to achieve this

Hope in dirt: report of the Fort Apache Workshop on Forensic Sedimentology Applications to Cultural Property Crime, 15—19 October 2018

A 2018 workshop on the White Mountain Apache Tribe lands in Arizona examined ways to enhance investigations into cultural property crime (CPC) through applications of rapidly evolving methods from archaeological science. CPC (also looting, graverobbing) refers to unauthorized damage, removal, or trafficking in materials possessing blends of communal, aesthetic, and scientific values. The Fort Apache workshop integrated four generally partitioned domains of CPC expertise: (1) theories of perpetrators’ motivations and methods; (2) recommended practice in sustaining public and community opposition to CPC; (3) tactics and strategies for documenting, investigating, and prosecuting CPC; and (4) forensic sedimentology—uses of biophysical sciences to link sediments from implicated persons and objects to crime scenes. Forensic sedimentology served as the touchstone for dialogues among experts in criminology, archaeological sciences, law enforcement, and heritage stewardship. Field visits to CPC crime scenes and workshop deliberations identified pathways toward integrating CPC theory and practice with forensic sedimentology’s potent battery of analytic methods

Pulmonary oedema measured by MRI correlates with late-phase response to allergen challenge

Purpose: Asthma is associated with reversible airway obstruction, leucocyte infiltration, airways hyperresponsiveness (AHR) and airways remodelling. Fluid accumulation causes pulmonary oedema contributing to airways obstruction. We examined the temporal relationship between the late asthmatic response (LAR) following allergen challenge of sensitised guinea-pigs and pulmonary oedema measured by magnetic resonance imaging (MRI). Materials and Methods: Ovalbumin (OVA) sensitised guinea-pigs received either a single OVA inhalation (acute) or nine OVA inhalations at 48 h intervals (chronic). Airways obstruction was measured as specific airways conductance (sGaw) by whole body plethysmography. AHR to inhaled histamine and bronchoalveolar lavage for leucocyte counts were measured 24 h after a single or the final chronic ovalbumin challenges. MRI was performed at intervals after OVA challenge and high intensity oedemic signals quantified. Results: Ovalbumin caused early bronchoconstriction, followed at 7 h by a LAR and at 24 h AHR and leucocyte influx. The bright intensity MRI oedema signal, peaking at 7 h, was significantly (P<0.05) greater after chronic (9.0±0.7x103 mm3) than acute OVA (7.6±0.2x103 mm3). Dexamethasone treatment before acute OVA abolished the AHR and LAR and significantly reduced eosinophils and the bright intensity MRI oedema from 9.1±1.0 to 6.4±0.3x103 mm3. Conclusion: We show a temporal relationship between oedema and the LAR and their parallel reduction, along with eosinophils and AHR, by dexamethasone. This suggests a close causative association between pulmonary oedema and impaired airways function