Increased number and altered phenotype of lymphatic vessels in peripheral lung compartments of patients with COPD

<p>Background De novo lymphatic vessel formation has recently been observed in lungs of patients with moderate chronic obstructive pulmonary disease (COPD). However, the distribution of lymphatic vessel changes among the anatomical compartments of diseased lungs is unknown. Furthermore, information regarding the nature of lymphatic vessel alterations across different stages of COPD is missing. This study performs a detailed morphometric characterization of lymphatic vessels in major peripheral lung compartments of patients with different severities of COPD and investigates the lymphatic expression of molecules involved in immune cell trafficking.</p> <p>Methods Peripheral lung resection samples obtained from patients with mild (GOLD stage I), moderate-severe (GOLD stage II-III), and very severe (GOLD stage IV) COPD were investigated for podoplanin-immunopositive lymphatic vessels in distinct peripheral lung compartments: bronchioles, pulmonary blood vessels and alveolar walls. Control subjects with normal lung function were divided into never smokers and smokers. Lymphatics were analysed by multiple morphological parameters, as well as for their expression of CCL21 and the chemokine scavenger receptor D6.</p> <p>Results The number of lymphatics increased by 133% in the alveolar parenchyma in patients with advanced COPD compared with never-smoking controls (p <0.05). In patchy fibrotic lesions the number of alveolar lymphatics increased 20-fold from non-fibrotic parenchyma in the same COPD patients. The absolute number of lymphatics per bronchiole and artery was increased in advanced COPD, but numbers were not different after normalization to tissue area. Increased numbers of CCL21- and D6-positive lymphatics were observed in the alveolar parenchyma in advanced COPD compared with controls (p <0.01). Lymphatic vessels also displayed increased mean levels of immunoreactivity for CCL21 in the wall of bronchioles (p < 0.01) and bronchiole-associated arteries (p < 0.05), as well as the alveolar parenchyma (p < 0.001) in patients with advanced COPD compared with never-smoking controls. A similar increase in lymphatic D6 immunoreactivity was observed in bronchioles (p <0.05) and alveolar parenchyma (p < 0.01).</p> <p>Conclusions This study shows that severe stages of COPD is associated with increased numbers of alveolar lymphatic vessels and a change in lymphatic vessel phenotype in major peripheral lung compartments. This novel histopathological feature is suggested to have important implications for distal lung immune cell traffic in advanced COPD.</p&gt

Effects of Dissimilar Metal Coupling, Potential Distribution, and Temper Condition on Galvanic Corrosion of 5086 Aluminum Alloy in Synthetic Seawater

The galvanic corrosion behavior of 5086 aluminum alloy in three tempers {Hll6, Hll7, H32) when coupled with more noble metals {1040 steel, naval brass, and Ti-150A titanium) and immersed in aerated synthetic seawater, was studied. Galvanic current density measurements, potentiodynamic polarization determinations, and optical and electron microscopic observations were made. Galvanic corrosion of 5086 aluminum was found to be independent of temper and to decrease in the order (of coupled metals) Ti > naval brass> 1040 steel. The effect of dissimilar metal coupling decreases with time due to the formation of corrosion or product deposits on both anodic and cathodic surfaces. Coverage of the surface of the aluminum (anodic) member of couples with corrosion products tends to promote the operation of local corrosion modes. Correlations have been made between corrosion product distribution and the distribution of dissolution attack by microscopic means, and the relation of these features to potential distribution is discussed.Naval Research, Metallurgy Program Office, Code 471N00014-77-WR-70215, NR-036-120Approved for public release; distribution is unlimited

PCN162 The Cost-Effectiveness of Second-Line Crizotinib in Eml4-Alk Rearranged Advanced Non-Small Cell Lung Cancer

Background: Snoring / sleep apnea are potentially life threatening breathing occurs during sleep. Little attention is being giving to this clinical condition. Objective: To determine the prevalence of snoring and risk factors associated with obstructive sleep apnea (OSA) among adults workers in two local governments of state, Nigeria Methodology: A cross - sectional survey of 121 young adult and adults working in two local governments of Ekiti state, south western Nigeria was carried out. A self administered questionnaire that was incorporated with Epworth Sleepiness Scale and Berlin Score was used to collect data on socio-demographic characteristics, information related to snoring, sleep related problems and their anthropometric. The Body Mass Index (BMI) and blood pressure of each participant were also measured. Results: Snoring was reported in forty nine (40.5%) of the participants. Their age ranges from 23 to 65 years, mean of 43.89 ± 8.53 SD. The proportion of males and Berlin score (high risk) were significantly (p < 0.001) higher among snores than non regression found sex (OR=7.791, 95% CI =2.971- 20.429), Berlin Score (high risk) (OR= 8.642, 95% CI= 3.159 - 23.639) as significant (P< 0.001) independent risk factors for OSA. Excessive day time sleepiness as determined by ESS score of the participants. Conclusion: The overall prevalence of snoring in this study was 40.5%. Snoring was found to increase with age, body mass index, male sex and those with high risk for Berlin score with high risk of developing Obstructive sleep apne

Growth Kinetics in a Phase Field Model with Continuous Symmetry

We discuss the static and kinetic properties of a Ginzburg-Landau spherically symmetric $O(N)$ model recently introduced (Phys. Rev. Lett. {\bf 75}, 2176, (1995)) in order to generalize the so called Phase field model of Langer. The Hamiltonian contains two $O(N)$ invariant fields $\phi$ and $U$ bilinearly coupled. The order parameter field $\phi$ evolves according to a non conserved dynamics, whereas the diffusive field $U$ follows a conserved dynamics. In the limit $N \to \infty$ we obtain an exact solution, which displays an interesting kinetic behavior characterized by three different growth regimes. In the early regime the system displays normal scaling and the average domain size grows as $t^{1/2}$, in the intermediate regime one observes a finite wavevector instability, which is related to the Mullins-Sekerka instability; finally, in the late stage the structure function has a multiscaling behavior, while the domain size grows as $t^{1/4}$.Comment: 9 pages RevTeX, 9 figures included, files packed with uufiles to appear on Phy. Rev.

Differential pathways to adult metabolic dysfunction following poor nutrition at two critical developmental periods in sheep

Epidemiological and experimental studies suggest early nutrition has long-term effects on susceptibility to obesity, cardiovascular and metabolic diseases. Small and large animal models confirm the influence of different windows of sensitivity, from fetal to early postnatal life, on offspring phenotype. We showed previously that undernutrition in sheep either during the first month of gestation or immediately after weaning induces differential, sex-specific changes in adult metabolic and cardiovascular systems. The current study aims to determine metabolic and molecular changes that underlie differences in lipid and glucose metabolism induced by undernutrition during specific developmental periods in male and female sheep. Ewes received 100% (C) or 50% nutritional requirements (U) from 1–31 days gestation, and 100% thereafter. From weaning (12 weeks) to 25 weeks, offspring were then fed either ad libitum (CC, UC) or were undernourished (CU, UU) to reduce body weight to 85% of their individual target. From 25 weeks, all offspring were fed ad libitum. A cohort of late gestation fetuses were studied after receiving either 40% nutritional requirements (1–31 days gestation) or 50% nutritional requirements (104–127 days gestation). Post-weaning undernutrition increased in vivo insulin sensitivity, insulin receptor and glucose transporter 4 expression in muscle, and lowered hepatic methylation at the delta-like homolog 1/maternally expressed gene 3 imprinted cluster in adult females, but not males. Early gestational undernutrition induced lower hepatic expression of gluconeogenic factors in fetuses and reduced in vivo adipose tissue insulin sensitivity in adulthood. In males, undernutrition in early gestation increased adipose tissue lipid handling mechanisms (lipoprotein lipase, glucocorticoid receptor expression) and hepatic methylation within the imprinted control region of insulin-like growth factor 2 receptor in adulthood. Therefore, undernutrition during development induces changes in mechanisms of lipid and glucose metabolism which differ between tissues and sexes dependent on the period of nutritional restriction. Such changes may increase later life obesity and dyslipidaemia risk

Short-term rhGH increases PIIINP, a biomarker of endothelial dysfunction

Objectives: In arterial hypertension, amino-terminal propeptide of type III procollagen (PIIINP) is elevated in arterial aneurysm tissue and associated with a poor prognosis following acute myocardial infarction (MI). Recombinant human growth hormone (rhGH) administration attenuates endothelial dysfunction but increases PIIINP. This study was conducted to establish if short-term rhGH administration affects PIIINP, endothelial function and selected cardiovascular disease (CVD) risk factors, in healthy males. Design: Method: Male subjects (n=48) were randomly assigned into two groups: (1): control group (C) n=24, mean ± SD, age 32 ± 11 years; height 1.8 ± 0.06 metres; (2): rhGH administration group (rhGH) n=24, mean ± SD, age 32 ± 9 years; height 1.8 ± 0.07 metres. Blood pressure (BP), heart rate (HR), arterial pulse wave velocity (APWV), and biochemical indices were investigated. Results: PIIINP (0.28±0.1 vs. 0.42±0.2, U/ml); Insulin like growth factor-I (159±54 vs. 323±93, ng.mL-1); resting HR (72±14 vs. 78±11, b.p.m.) and rate pressure product (RPP) (90±18 vs. 97±14, bpm x mm.Hg x 10-2) all significantly increased (P<0.05). Total cholesterol (4.7±0.9 vs. 4.4±0.7, mmol.L-1); high sensitivity C-reactive protein (1.77±2.1 vs. 1.29±1.6, mg.L-1); serum homocysteine (13.2±4.0 vs. 11.7±3.1, μmol.L-1) and APWV (9.97±1.38 vs. 9.18±1.6, m.s-1) all significantly decreased (P<0.05). Conclusion: Paradoxically, there was an improvement in CVD inflammatory markers and APWV; but PIIINP and resting RPP increased. Elevated PIIINP may have a confounding adverse effect on the endothelium, but may also provide clinical prognostic information in monitoring arterial hypertension, left ventricular function in the sub-acute phase following MI and endothelial function in aortic aneurysms

The self-consistent bounce: an improved nucleation rate

We generalize the standard computation of homogeneous nucleation theory at zero temperature to a scenario in which the bubble shape is determined self-consistently with its quantum fluctuations. Studying two scalar models in 1+1 dimensions, we find the self-consistent bounce by employing a two-particle irreducible (2PI) effective action in imaginary time at the level of the Hartree approximation. We thus obtain an effective single bounce action which determines the rate exponent. We use collective coordinates to account for the translational invariance and the growth instability of the bubble and finally present a new nucleation rate prefactor. We compare the results with those obtained using the standard 1-loop approximation and show that the self-consistent rate can differ by several orders of magnitude.Comment: 28 pages, revtex, 7 eps figure

Electromagnetic Casimir densities for a wedge with a coaxial cylindrical shell

Vacuum expectation values of the field square and the energy-momentum tensor for the electromagnetic field are investigated for the geometry of a wedge with a coaxal cylindrical boundary. All boundaries are assumed to be perfectly conducting and both regions inside and outside the shell are considered. By using the generalized Abel-Plana formula, the vacuum expectation values are presented in the form of the sum of two terms. The first one corresponds to the geometry of the wedge without the cylindrical shell and the second term is induced by the presence of the shell. The vacuum energy density induced by the shell is negative for the interior region and is positive for the exterior region. The asymptotic behavior of the vacuum expectation values are investigated in various limiting cases. It is shown that the vacuum forces acting on the wedge sides due to the presence of the cylindrical boundary are always attractive.Comment: 21 pages, 7 figure