Investigation of guided wave propagation in pipes fully- and partially-embedded in concrete

The application of long-range guided-wave testing to pipes embedded in concrete results in unpredictable test-ranges. The influence of the circumferential extent of the embedding-concrete around a steel pipe on the guided wave propagation is investigated. An analytical model is used to study the axisymmetric fully embedded pipe case, while explicit finite-element and semi-analytical finite-element simulations are utilised to investigate a partially embedded pipe. Model predictions and simulations are compared with full-scale guided-wave tests. The transmission-loss of the T(0,1)-mode in an 8 in. steel pipe fully embedded over an axial length of 0.4 m is found to be in the range of 32–36 dB while it reduces by a factor of 5 when only 50% of the circumference is embedded. The transmission-loss in a fully embedded pipe is mainly due to attenuation in the embedded section while in a partially embedded pipe it depend strongly on the extent of mode-conversion at entry to the embedded-section; low loss modes with energy concentrated in the region of the circumference not-covered with concrete have been identified. The results show that in a fully embedded pipe, inspection beyond a short distance will not be possible, whereas when the concrete is debonded over a fraction of the pipe circumference, inspection of substantially longer lengths may be possible

Roflumilast Prevents the Metabolic Effects of Bleomycin-Induced Fibrosis in a Murine Model

<div><p>Fibrotic remodeling is a process common to chronic lung diseases such as chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, acute respiratory distress syndrome and asthma. Based on preclinical studies phosphodiesterase 4 (PDE4) inhibitors may exhibit beneficial anti-inflammatory and anti-remodeling properties for the treatment of these respiratory disorders. Effects of PDE4 inhibitors on changes in the lung metabolome in models of pulmonary fibrotic remodeling have not yet been explored. This work studies the effects of the PDE4 inhibitor roflumilast on changes in the lung metabolome in the common murine model of bleomycin-induced lung fibrosis by nuclear magnetic resonance (NMR) metabolic profiling of intact lung tissue. Metabolic profiling reveals strong differences between fibrotic and non-fibrotic tissue. These differences include increases in proline, glycine, lactate, taurine, phosphocholine and total glutathione and decreases in global fatty acids. In parallel, there was a loss in plasma BH4. This profile suggests that bleomycin produces alterations in the oxidative equilibrium, a strong inflammatory response and activation of the collagen synthesis among others. Roflumilast prevented most of these metabolic effects associated to pulmonary fibrosis suggesting a favorable anti-fibrotic profile.</p></div

Scores plot of Principal Component (PC) Analysis to compare the metabolome of murine lung control tissue (white circles), lung tissue from animals treated with bleomycin + vehicle (black circles), lung tissue from animals treated with bleomycin + roflumilast at 1 mg/kg/day (gray triangles) and lung tissue from animals treated with bleomycin + roflumilast at 5 mg/kg/day (gray squares).

<p>PC1 and PC2 represent the two principal component analysis used to group individuals according with the amount of different metabolites in lung tissue.</p

Effects of roflumilast on bleomycin-induced metabolites related to fatty acids, phospholipids and uracil in mouse lungs.

<p>Mice received a single dose of bleomycin (3.75 U/kg) intratracheally at day 1 and roflumilast (1 or 5 mg/kg/day p.o., once daily) or vehicle was administered from day 1 to 14 (<i>preventive protocol</i>) until analysis at day 14. Total fatty acids (A), polyunsaturated fatty acids (B), phosphocholine (C), phosphoethanolamine (D), and uracil (E) metabolites were assessed as described in Methods in murine lung control tissue (n = 17), lung tissue from animals treated with bleomycin + vehicle (n = 14), lung tissue from animals treated with bleomycin + roflumilast 1 mg/kg/day (n = 8) and lung tissue from animals treated with bleomycin + roflumilast 5 mg/kg/day (n = 4). Results are given as mean ± SD. *P<0.05 versus control, **P<0.02 versus control, #P<0.05 versus bleomycin + vehicle.</p

Effects of roflumilast on bleomycin-induced metabolites related to oxidative stress in mouse lungs.

<p>Mice received a single dose of bleomycin (3.75 U/kg) intratracheally at day 1 and roflumilast (1 or 5 mg/kg/day p.o., once daily) or vehicle was administered from day 1 to 14 (<i>preventive protocol</i>) until analysis at day 14. (A) Total glutathione and (B) taurine were assessed by NMR in murine lung control tissue (n = 17), lung tissue from animals treated with bleomycin + vehicle (n = 14), lung tissue from animals treated with bleomycin + roflumilast at 1 mg/kg/day (n = 8) and lung tissue from animals treated with bleomycin + roflumilast at 5 mg/kg/day (n = 4). Plasma levels of (C) BH4 and (D) BH4/BH2 ratio were measured by high performance liquid chromatography (HPLC). Results are given as mean ± SD. *P<0.05 versus control, **P<0.02 versus control, #P<0.05 versus bleomycin + vehicle.</p

Effects of roflumilast on bleomycin-induced metabolites related to branched chain amino acids leucine and isoleucine, glucose and lactate in mouse lungs.

<p>Mice received a single dose of bleomycin (3.75 U/kg) intratracheally at day 1 and roflumilast (1 or 5 mg·kg^-1·d^-1 p.o., once daily) or vehicle was administered from day 1 to 14 (<i>preventive protocol</i>) until analysis at day 14. Leucine (A), isoleucine (B), glucose (C), and lactate (D) were assessed as described in Methods in murine lung control tissue (n = 17), lung tissue from animals treated with bleomycin + vehicle (n = 14), lung tissue from animals treated with bleomycin + roflumilast 1 mg/kg/day (n = 8) and lung tissue from animals treated with bleomycin + roflumilast 5 mg/kg/day (n = 4). Results are given as mean ± SD *P<0.05 versus control, **P<0.02 versus control, #P<0.05 versus bleomycin + vehicle.</p

Effect of different commercial parenteral lipid emulsions on Lipopolysaccharide (LPS)-induced IL-6 and TNFα secretion in human monocytes.

<p>Human monocytes were isolated from healthy subjects and incubated in presence or absence of lipid emulsions Omegaven® 10%, Lipofundin MCT/LCT® 20%, ClinOleic® 20% or SMOFlipid® 20% at different dilutions, for 30 min followed by LPS 1 µg/mL stimulation for additional 24 hours. (A) IL-6 and (B) TNFα were measured in cell culture supernatants. The effect of lipid emulsions without stimulus was tested at 1/10 dilution. Results are expressed as means ± SEM of six independent experiments. *<i>p</i><0.05 related to the control group. #<i>p</i><0.05 values below stimulus; ⊥<i>p</i><0.05 values above the stimulus.</p

Anti-Inflammatory and Anti-Fibrotic Profile of Fish Oil Emulsions Used in Parenteral Nutrition-Associated Liver Disease

<div><p>Home parenteral nutrition (PN) is associated with many complications including severe hepatobiliary dysfunction. Commercial ω-6 fatty acid-soybean based-lipid emulsions in PN may mediate long term PN associate liver disease (PNALD) whereas ω-3-fish oil parenteral emulsions have shown to reverse PNALD in children. However, its clinical effectiveness in adults has been scarcely reported. In this work, we study the role of soybean and fish oil lipid commercial emulsions on inflammatory and profibrotic liver markers in adults with long term PNALD and in <i>in vitro</i> cellular models. Inflammatory and profibrotic markers were measured in serum of ten adults with long term PNALD and in culture supernatants of monocytes. Liver epithelial to mesenchymal transition (EMT) was induced by transforming growth factor beta 1 (TGFβ1) to evaluate <i>in vitro</i> liver fibrosis. Omegaven®, a 100% fish oil commercial emulsion, was infused during four months in two patients with severe long term PNALD reversing, at the first month, the inflammatory, profibrotic and clinical parameters of PNALD. The effect was maintained during the treatment course but impaired when conventional lipid emulsions were reintroduced. The other patients under chronic soybean oil-based PN showed elevated inflammatory and profibrotic parameters. <i>In vitro</i> human monocytes stimulated with lipopolysaccharide induced a strong inflammatory response that was suppressed by Omegaven®, but increased by soybean emulsions. In other experiments, TGFβ1 induced EMT that was suppressed by Omegaven® and enhanced by soybean oil lipid emulsions. Omegaven® improves clinical, anti-inflammatory and anti-fibrotic parameters in adults with long-term home PNALD.</p></div

Representative NMR spectra (panels i, ii, iii, iv) for murine lung control tissue (panel i), lung tissue from animals treated with bleomycin + vehicle (panel ii), lung tissue from animals treated with bleomycin + roflumilast 1 mg/kg/day (panel iii) and lung tissue from animals treated with bleomycin + roflumilast 5 mg/kg/day (panel iv).

<p>Resonances belonging to most relevant metabolites have been labeled in the spectra (1: Fatty acids, 2: Leucine, 3:Isoleucine, 4:Lactate, 5:Alanine, 6:Total glutathione, 7:Creatine, 8:Choline, 9:Phosphocholine, 10:Taurine, 11:Glycine, 12:Glucose).</p

Effect of different commercial parenteral lipid emulsions on Lipopolysaccharide (LPS)-induced TGFβ1 and MMP-9 secretion in human monocytes.

<p>Human monocytes were isolated from healthy subjects and incubated in presence or absence of lipid emulsions Omegaven® 10%, Lipofundin MCT/LCT® 20%, ClinOleic® 20% or SMOFlipid® 20% at different dilutions, for 30 min followed by LPS 1 µg/mL stimulation for additional 24 hours. (A) TGFβ1 and (B) MMP-9 were measured in cell culture supernatants. The effect of lipid emulsions without stimulus was tested at 1/10 dilution. Results are expressed as means ± SEM of six independent experiments. *<i>p</i><0.05 related to the control group. #<i>p</i><0.05 values below stimulus; ⊥<i>p</i><0.05 values above the stimulus.</p