2,076 research outputs found
Metformin reduces airway glucose permeability and hyperglycaemia-induced Staphylococcus aureus load independently of effects on blood glucose
Background Diabetes is a risk factor for respiratory infection, and hyperglycaemia is associated with increased glucose in airway surface liquid and risk of Staphylococcus aureus infection.
Objectives To investigate whether elevation of basolateral/blood glucose concentration promotes airway Staphylococcus aureus growth and whether pretreatment with the antidiabetic drug metformin affects this relationship.
Methods Human airway epithelial cells grown at air–liquid interface (±18 h pre-treatment, 30 μM–1 mM metformin) were inoculated with 5×105 colony-forming units (CFU)/cm2 S aureus 8325-4 or JE2 or Pseudomonas aeruginosa PA01 on the apical surface and incubated for 7 h. Wild-type C57BL/6 or db/db (leptin receptor-deficient) mice, 6–10 weeks old, were treated with intraperitoneal phosphate-buffered saline or 40 mg/kg metformin for 2 days before intranasal inoculation with 1×107 CFU S aureus. Mice were culled 24 h after infection and bronchoalveolar lavage fluid collected.
Results Apical S aureus growth increased with basolateral glucose concentration in an in vitro airway epithelia–bacteria co-culture model. S aureus reduced transepithelial electrical resistance (RT) and increased paracellular glucose flux. Metformin inhibited the glucose-induced growth of S aureus, increased RT and decreased glucose flux. Diabetic (db/db) mice infected with S aureus exhibited a higher bacterial load in their airways than control mice after 2 days and metformin treatment reversed this effect. Metformin did not decrease blood glucose but reduced paracellular flux across ex vivo murine tracheas.
Conclusions Hyperglycaemia promotes respiratory S aureus infection, and metformin modifies glucose flux across the airway epithelium to limit hyperglycaemia-induced bacterial growth. Metformin might, therefore, be of additional benefit in the prevention and treatment of respiratory infection
Elevated Paracellular Glucose Flux across Cystic Fibrosis Airway Epithelial Monolayers Is an Important Factor for Pseudomonas aeruginosa Growth.
People with cystic fibrosis (CF) who develop related diabetes (CFRD) have accelerated pulmonary decline, increased infection with antibiotic-resistant Pseudomonas aeruginosa and increased pulmonary exacerbations. We have previously shown that glucose concentrations are elevated in airway surface liquid (ASL) of people with CF, particularly in those with CFRD. We therefore explored the hypotheses that glucose homeostasis is altered in CF airway epithelia and that elevation of glucose flux into ASL drives increased bacterial growth, with an effect over and above other cystic fibrosis transmembrane conductance regulator (CFTR)-related ASL abnormalities. The aim of this study was to compare the mechanisms governing airway glucose homeostasis in CF and non-CF primary human bronchial epithelial (HBE) monolayers, under normal conditions and in the presence of Ps. aeruginosa filtrate. HBE-bacterial co-cultures were performed in the presence of 5 mM or 15 mM basolateral glucose to investigate how changes in blood glucose, such as those seen in CFRD, affects luminal Ps. aeruginosa growth. Calu-3 cell monolayers were used to evaluate the potential importance of glucose on Ps. aeruginosa growth, in comparison to other hallmarks of the CF ASL, namely mucus hyperviscosity and impaired CFTR-dependent fluid secretions. We show that elevation of basolateral glucose promotes the apical growth of Ps. aeruginosa on CF airway epithelial monolayers more than non-CF monolayers. Ps. aeruginosa secretions elicited more glucose flux across CF airway epithelial monolayers compared to non-CF monolayers which we propose increases glucose availability in ASL for bacterial growth. In addition, elevating basolateral glucose increased Ps. aeruginosa growth over and above any CFTR-dependent effects and the presence or absence of mucus in Calu-3 airway epithelia-bacteria co-cultures. Together these studies highlight the importance of glucose as an additional factor in promoting Ps. aeruginosa growth and respiratory infection in CF disease
Patterns of self-reported behaviour change associated with receiving voluntary counselling and testing in a longitudinal study from Manicaland, Zimbabwe.
Voluntary counselling and testing (VCT) is promoted as a potential HIV prevention measure. We describe trends in uptake of VCT for HIV, and patterns of subsequent behaviour change associated with receiving VCT in a population-based open cohort in Manicaland, Zimbabwe. The relationship between receipt of VCT and subsequent reported behaviour was analysed using generalized linear models with random effects. At the third survey, 8.6% of participants (1,079/12,533), had previously received VCT. Women who received VCT, both those positive and negative, reduced their reported number of new partners. Among those testing positive, this risk reduction was enhanced with time since testing. Among men, no behavioural risk reduction associated with VCT was observed. Significant increases in consistent condom use, with regular or non-regular partners, following VCT, were not observed. This study suggests that, among women, particularly those who are infected, behavioural risk reduction does occur following VCT
Radiocarbon dating of methane and carbon dioxide evaded from a temperate peatland stream
Streams draining peatlands export large quantities of carbon in different chemical forms and
are an important part of the carbon cycle. Radiocarbon (14C) analysis/dating provides unique
information on the source and rate that carbon is cycled through ecosystems, as has recently
been demonstrated at the air-water interface through analysis of carbon dioxide (CO2) lost
from peatland streams by evasion (degassing). Peatland streams also have the potential to
release large amounts of methane (CH4) and, though 14C analysis of CH4 emitted by ebullition
(bubbling) has been previously reported, diffusive emissions have not. We describe methods
that enable the 14C analysis of CH4 evaded from peatland streams. Using these methods, we
investigated the 14C age and stable carbon isotope composition of both CH4 and CO2 evaded
from a small peatland stream draining a temperate raised mire. Methane was aged between
1617-1987 years BP, and was much older than CO2 which had an age range of 303-521 years
BP. Isotope mass balance modelling of the results indicated that the CO2 and CH4 evaded
from the stream were derived from different source areas, with most evaded CO2 originating
from younger layers located nearer the peat surface compared to CH4. The study demonstrates
the insight that can be gained into peatland carbon cycling from a methodological
development which enables dual isotope (14C and 13C) analysis of both CH4 and CO2 collected
at the same time and in the same way
Analytic structure of the S-matrix for singular quantum mechanics
The analytic structure of the S-matrix of singular quantum mechanics is examined within a multichannel framework, with primary focus on its dependence with respect to a parameter (Ω) that determines the boundary conditions. Specifically, a characterization is given in terms of salient mathematical and physical properties governing its behavior. These properties involve unitarity and associated current-conserving Wronskian relations, time-reversal invariance, and Blaschke factorization. The approach leads to an interpretation of effective nonunitary solutions in singular quantum mechanics and their determination from the unitary family.Fil: Camblong, Horacio E.. University of San Francisco; Estados UnidosFil: Epele, Luis Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Física. Laboratorio de Física Teórica; ArgentinaFil: Fanchiotti, Huner. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Física. Laboratorio de Física Teórica; ArgentinaFil: García Canal, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Física. Laboratorio de Física Teórica; Argentin
Discrepancies between UN models and DHS survey estimates of maternal orphan prevalence: insights from analyses of survey data from Zimbabwe
Finding community structure in networks using the eigenvectors of matrices
We consider the problem of detecting communities or modules in networks,
groups of vertices with a higher-than-average density of edges connecting them.
Previous work indicates that a robust approach to this problem is the
maximization of the benefit function known as "modularity" over possible
divisions of a network. Here we show that this maximization process can be
written in terms of the eigenspectrum of a matrix we call the modularity
matrix, which plays a role in community detection similar to that played by the
graph Laplacian in graph partitioning calculations. This result leads us to a
number of possible algorithms for detecting community structure, as well as
several other results, including a spectral measure of bipartite structure in
networks and a new centrality measure that identifies those vertices that
occupy central positions within the communities to which they belong. The
algorithms and measures proposed are illustrated with applications to a variety
of real-world complex networks.Comment: 22 pages, 8 figures, minor corrections in this versio
Electronic response of aligned multishell carbon nanotubes
We report calculations of the effective electronic response of aligned
multishell carbon nanotubes. A local graphite-like dielectric tensor is
assigned to every point of the multishell tubules, and the effective transverse
dielectric function of the composite is computed by solving Maxwell's
equations. Calculations of both real and imaginary parts of the effective
dielectric function are presented, for various values of the filling fraction
and the ratio of the internal and external radii of hollow tubules. Our full
calculations indicate that the experimentally measured macroscopic dielectric
function of carbon nanotube materials is the result of a strong electromagnetic
coupling between the tubes, which cannot be accounted for with the use of
simplified effective medium theories. The presence of surface plasmons is
investigated, and both optical absorption cross sections and energy-loss
spectra of aligned tubules are calculated.Comment: 4 pages, 4 figures, to appear in Phys. Rev.
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