Smoking in asthma is associated with elevated levels of corticosteroid resistant sputum cytokines—an exploratory study

<p>Background: Current cigarette smoking is associated with reduced acute responses to corticosteroids and worse clinical outcomes in stable chronic asthma. The mechanism by which current smoking promotes this altered behavior is currently unclear. Whilst cytokines can induce corticosteroid insensitivity in-vitro, how current and former smoking affects airway cytokine concentrations and their responses to oral corticosteroids in stable chronic asthma is unclear.</p> <p>Objectives: To examine blood and sputum cytokine concentrations in never, ex and current smokers with asthma before and after oral corticosteroids.</p> <p>Methods: Exploratory study utilizing two weeks of oral dexamethasone (equivalent to 40 mg/day prednisolone) in 22 current, 21 never and 10 ex-smokers with asthma. Induced sputum supernatant and plasma was obtained before and after oral dexamethasone. 25 cytokines were measured by multiplex microbead system (Invitrogen, UK) on a Luminex platform.</p> <p>Results: Smokers with asthma had elevated sputum cytokine interleukin (IL) -6, -7, and -12 concentrations compared to never smokers with asthma. Few sputum cytokine concentrations changed in response to dexamethasone IL-17 and IFNα increased in smokers, CCL4 increased in never smokers and CCL5 and CXCL10 reduced in ex-smokers with asthma. Ex-smokers with asthma appeared to have evidence of an ongoing corticosteroid resistant elevation of cytokines despite smoking cessation. Several plasma cytokines were lower in smokers wi</p> <p>Conclusion: Cigarette smoking in asthma is associated with a corticosteroid insensitive increase in multiple airway cytokines. Distinct airway cytokine profiles are present in current smokers and never smokers with asthma and could provide an explanatory mechanism for the altered clinical behavior observed in smokers with asthma.</p&gt

Hypoxia in atherogenesis

The anoxemia theory proposes that an imbalance between the demand for and supply of oxygen in the arterial wall is a key factor in the development of atherosclerosis. There is now substantial evidence that there are regions within the atherosclerotic plaque in which profound hypoxia exists; this may fundamentally change the function, metabolism, and responses of many of the cell types found within the developing plaque and whether the plaque will evolve into a stable or unstable phenotype. Hypoxia is characterized in molecular terms by the stabilization of hypoxia-inducible factor (HIF) 1a, a subunit of the heterodimeric nuclear transcriptional factor HIF-1 and a master regulator of oxygen homeostasis. The expression of HIF-1 is localized to perivascular tissues, inflammatory macrophages, and smooth muscle cells adjacent to the necrotic core of atherosclerotic lesions and regulates several genes that are important to vascular function including vascular endothelial growth factor, nitric oxide synthase, endothelin-1, and erythropoietin. This review summarizes the effects of hypoxia on the functions of cells involved in atherogenesis and the evidence for its potential importance from experimental models and clinical studies

The optical afterglow of the short gamma-ray burst GRB 050709

It has long been known that there are two classes of gamma-ray bursts (GRBs), mainly distinguished by their durations. The breakthrough in our understanding of long-duration GRBs (those lasting more than ~2 s), which ultimately linked them with energetic Type Ic supernovae, came from the discovery of their long-lived X-ray and optical afterglows, when precise and rapid localizations of the sources could finally be obtained. X-ray localizations have recently become available for short (duration <2 s) GRBs, which have evaded optical detection for more than 30 years. Here we report the first discovery of transient optical emission (R-band magnitude ~23) associated with a short burst; GRB 050709. The optical afterglow was localized with subarcsecond accuracy, and lies in the outskirts of a blue dwarf galaxy. The optical and X-ray afterglow properties 34 h after the GRB are reminiscent of the afterglows of long GRBs, which are attributable to synchrotron emission from ultrarelativistic ejecta. We did not, however, detect a supernova, as found in most nearby long GRB afterglows, which suggests a different origin for the short GRBs.Comment: 11 pages, 3 figures, press material at http://www.astro.ku.dk/dark

"Now he walks and walks, as if he didn't have a home where he could eat": food, healing, and hunger in Quechua narratives of madness

In the Quechua-speaking peasant communities of southern Peru, mental disorder is understood less as individualized pathology and more as a disturbance in family and social relationships. For many Andeans, food and feeding are ontologically fundamental to such relationships. This paper uses data from interviews and participant observation in a rural province of Cuzco to explore the significance of food and hunger in local discussions of madness. Carers’ narratives, explanatory models, and theories of healing all draw heavily from idioms of food sharing and consumption in making sense of affliction, and these concepts structure understandings of madness that differ significantly from those assumed by formal mental health services. Greater awareness of the salience of these themes could strengthen the input of psychiatric and psychological care with this population and enhance knowledge of the alternative treatments that they use. Moreover, this case provides lessons for the global mental health movement on the importance of openness to the ways in which indigenous cultures may construct health, madness, and sociality. Such local meanings should be considered by mental health workers delivering services in order to provide care that can adjust to the alternative ontologies of sufferers and carers

A radiographic measurement of left atrial size in dogs

The dimensions of the left atrium in cases with mitral regurgitation are an indirect measurement of its severity. The objective of this study was to evaluate the value of a new radiographic measurement, the radiographic left atrial dimension (RLAD), for detecting left atrial enlargement (LAE) in dogs. Thirty one dogs without LAE and 46 dogs with LAE were recruited in a prospective fashion. Reference left atrium dimension was measured by standard left atrium to aorta ratio (LA/Ao) by 2D echocardiography. LAE was considered if LA/Ao > 1.6. Left atrium dimension was then quantified on lateral radiographs by measuring RLAD. Vertebral heart size (VHS) was measured and RLAD was obtained by drawing a line bisecting the 90 degrees angle defined by the long and short cardiac axes lines of the VHS, up to the dorsal edge of the left atrium and comparing its length to T4’s vertebral body length. The correlation of VHS and RLAD methods with LA/Ao was estimated, as well as their sensitivity and specificity for detecting LAE. Receiver Operating Characteristic (ROC) curves were used to estimate the optimal decision criteria for each method

Genetic diversity of Brazilian isolates of feline immunodeficiency virus

We isolated Feline immunodeficiency virus (FIV) from three adult domestic cats, originating from two open shelters in Brazil. Viruses were isolated from PBMC following co-cultivation with the feline T-lymphoblastoid cell line MYA-1. All amplified env gene products were cloned directly into pGL8MYA. The nucleic acid sequences of seven clones were determined and then compared with those of previously described isolates. The sequences of all of the Brazilian virus clones were distinct and phylogenetic analysis revealed that all belong to subtype B. Three variants isolated from one cat and two variants were isolated from each of the two other cats, indicating that intrahost diversity has the potential to pose problems for the treatment and diagnosis of FIV infection

The use of a physiologically based pharmacokinetic model to evaluate deconvolution measurements of systemic absorption

BACKGROUND: An unknown input function can be determined by deconvolution using the systemic bolus input function (r) determined using an experimental input of duration ranging from a few seconds to many minutes. The quantitative relation between the duration of the input and the accuracy of r is unknown. Although a large number of deconvolution procedures have been described, these routines are not available in a convenient software package. METHODS: Four deconvolution methods are implemented in a new, user-friendly software program (PKQuest, ). Three of these methods are characterized by input parameters that are adjusted by the user to provide the "best" fit. A new approach is used to determine these parameters, based on the assumption that the input can be approximated by a gamma distribution. Deconvolution methodologies are evaluated using data generated from a physiologically based pharmacokinetic model (PBPK). RESULTS AND CONCLUSIONS: The 11-compartment PBPK model is accurately described by either a 2 or 3-exponential function, depending on whether or not there is significant tissue binding. For an accurate estimate of r the first venous sample should be at or before the end of the constant infusion and a long (10 minute) constant infusion is preferable to a bolus injection. For noisy data, a gamma distribution deconvolution provides the best result if the input has the form of a gamma distribution. For other input functions, good results are obtained using deconvolution methods based on modeling the input with either a B-spline or uniform dense set of time points