Long-term Variability of Desmosine/Isodesmosine as Biomarker in Alpha-1-antritrypsin Deficiency–related COPD

Desmosine and isodesmosine are products of elastin breakdown which are candidate biomarkers to measure lung destruction in COPD. Data exist on the burden of desmosines in urine and plasma in COPD but long-term changes have never been investigated. We determined the changes of desmosine levels over 14 months in urine and plasma of patients with type ZZ alpha-1-antitryspsin deficiency-related COPD. Urines and plasma for determination of desmosines were collected from 11 ex-smokers with moderate/severe emphysema at monthly intervals for 14 months. Spirometry and gas transfer were assessed at baseline and 6-month intervals. At baseline and month 14, eleven healthy partners of patients volunteered to give a blood sample for detection of desmosines. Desmosines were determined by capillary electrophoresis combined with laser-induced fluorescence. Urine and plasma desmosines were significantly increased after 14 months in patients (p = 0.027 and p = 0.0005, respectively). Plasma desmosines of healthy partners at baseline were 4-fold lower than from patients and not significantly different from values at month 14. Only a significant decline in lung gas transfer occurred in patients (p = 0.015). The variability of desmosines was higher in urine than in plasma (coefficient of variation 0.17 and 0.087, respectively). As longitudinal desmosine changes likely reflect the elevated elastic fiber turnover associated with the progression of lung damage and destruction in COPD, they appear to be a suitable marker for application in long-term studies. Plasma desmosines were more stable long-term biomarkers than desmosines in urine.     

Development of HLA-matched vascular grafts utilizing decellularized human umbilical artery

Worldwide, there is a great need of small diameter vascular grafts that can be used in human disorders such as cardiovascular and peripheral vascular disease. Until now, severe adverse reactions are caused from the use of synthetic or animal derived grafts, while the use of autologous vessels is restricted only in a small number of patients. The limited availability of the vessels might be resolved by the use of HLA-matched vascular grafts utilizing the decellularized human umbilical arteries. In this study, human umbilical arteries were decellularized and then repopulated with Mesenchymal Stem Cells. The HLA-genotype of the repopulated grafts, analyzed by Next Generation Sequencing technology, indicated their successful production. The HLA-matched vascular grafts could be generated efficiently and might be used in personalized medicine.     

Immunoreactive Elastin in benign breast tissues

Summary Immunohistological localisation of elastin was achieved by means of the peroxidase-antiperoxidase method after preliminary trypsinisation of sections from 48 benign breast biopsies. The procedure allows retrospective examination of routinely formalin-fixed, paraffin-embedded breast tissue. In general the immunolocalisation of elastin showed a close microanatomical correlation with the fibres demonstrable in sections from the same blocks by standard elastic-fibre stains. Discrepancies between elastic-fibre stains and elastin immunoreactivity appear to relate to the enhanced avidity of the antibody for immature elastin. In this way sites of recent synthesis of elastin were demonstrated in the inner zone of the periductal elastica, sclerosing adenosis, and in the internal elastic lamina of breast arteries which displayed reduplication of the internal elastic lamina or intimal proliferation.     

Age-related changes in arterial wall mechanics and composition of NIA Fischer rats

Segments of carotid and tail arteries and descending thoracic aorta were obtained from the NIA colony of Fischer rats at ages 3, 12, 24 and 30 months. Measurements of pressure and diameter were made on intact cylindrical segments under conditions of active (147 mM K⁺ and pssive (Ca²⁺ -free and 2 mM EGTA) smooth muscle. These data were used to compute active and passive mechanics. Contiguous segments were used for the analysis of connective tissue, water and electrolyte contents. Passive stiffness of the carotid and tail arteries increased monotonically with increasing age. Collagen content in the aorta and tail artery generally increased with age, while elastin content decreased in the aorta and carotid artery. The ratio of collagen to elastin increased at all sites with age. Maximum values of active stress response (force development) increased from 3 to 12 months for the carotid artery, but decreased with age (at 24 and 30 months compared to 3 and 12 months) for the tail artery. Changes in relative cell content were such that active cellular force development was the same at all ages for the carotid artery but was smaller at 24 and 30 months compared to the younger animals for the tail artery. Decreased cellular force development by arterial smooth muscle is not an anatomically uniform finding in this animal model.     

Suture-reinforced electrospun polydioxanone-elastin small-diameter tubes for use in vascular tissue engineering: a feasibility study

This study characterizes the cross-linking of electrospun elastin and the mechanical properties of suture-reinforced 1.5mm internal diameter electrospun tubes composed of blended polydioxanone (PDO) and soluble elastin. Several tube configurations were tested to assess the effects of reinforcement on tube mechanical properties. Between the electrospun layers of each double-layered prosthetic, zero, one or two 6-0 sutures were wound, maintaining 1mm spacing with a pitch of 9 degrees . Single-layered tubes without suture were also examined. Samples were cross-linked and tested for compliance and burst strength. Compliance decreased significantly (p <0.05) and burst strength significantly increased (p <0.01) with reinforcement. Uncross-linked tubes were also tested to determine the effects of cross-linking. Results demonstrated that cross-linking significantly decreases burst strength (p <0.01), while decreases in compliance for cross-linked tubes were not significant. Cross-linked suture-reinforced PDO-elastin tubes had burst pressures more than 10 times greater than normal systolic pressures and exhibited a range of compliance values, including those matching native artery. These tubes display many characteristics of the "ideal" small-diameter graft, having mechanical properties that can be tailored to match those desired in vascular replacement applications.     

Immunohistochemical Demonstration of Type II Collagen in the Chondroid Tissue of Pleomorphic Adenomas of the Salivary Glands

A study was done to investigate the presence of type II collagen and elastin in the metaplastic chondroid tissue of 21 pleornorphic adenomas of the major and minor salivary glands. Type II collagen was detected with anti-bovine type II collagen antibody after double digestion of histological sections with trypsin and hyaluronidase. The immunoreaction was positive in the chondrocytic cells and intercellular matrix. Elastic fibers in the chondroid tissue were found by orcein staining; they were scarce and randomly distributed. Although the presence of type II collagen and elastin in the metaplastic chondroid tissue is not directly implicated in the genesis of the tumor, it reveals a unique and high grade of cellular differentiation in comparison with true cartilage.     

Parametric and Nonparametric Nonlinear System Identification of Lung Tissue Strip Mechanics

Lung parenchyma is a soft biological material composed of many interacting elements such as the interstitial cells, extracellular collagen–elastin fiber network, and proteoglycan ground substance. The mechanical behavior of this delicate structure is complex showing several mild but distinct types of nonlinearities and a fractal-like long memory stress relaxation characterized by a power-law function. To characterize tissue nonlinearity in the presence of such long memory, we investigated the robustness and predictive ability of several nonlinear system identification techniques on stress–strain data obtained from lung tissue strips with various input wave forms. We found that in general, for a mildly nonlinear system with long memory, a nonparametric nonlinear system identification in the frequency domain is preferred over time-domain techniques. More importantly, if a suitable parametric nonlinear model is available that captures the long memory of the system with only a few parameters, high predictive ability with substantially increased robustness can be achieved. The results provide evidence that the first-order kernel of the stress–strain relationship is consistent with a fractal-type long memory stress relaxation and the nonlinearity can be described as a Wiener-type nonlinear structure for displacements mimicking tidal breathing. © 1999 Biomedical Engineering Society. PAC99: 8719Rr, 8710+e     

Evaluation of arterial grafts prior to coronary bypass in pseudoxanthoma elasticum

Pseudoxanthoma elasticum is a rare, inherited connective tissue disorder associated with coronary and peripheral arterial disease and accelerated atherosclerosis in medium sized arteries. We describe 110-month symptom-free survival in a patient with pseudoxanthoma elasticum who underwent coronary bypass using the left internal mammary artery at 56 years of age. The vessel was evaluated pre-operatively with angiography to determine suitability, and he has not required further investigation or intervention due to lack of symptoms.     

Abnormal colonic cholinergic and nitrergic activities in relation to elastosis in uncomplicated diverticular disease

I read with interest the review on the pathogenesis of diverticular disease by Commane et al in World J Gastroenterol 2009;15(20):2479-2488.However,I would like to discuss several important errors that the authors made whilst citing information from previously published work on the neuromuscular dysfunction in the disease.     

Spontaneous Development and Rupture of Pulmonary Artery Aneurysm: A Rare Complication in an Infant with Peripheral Pulmonary Artery Stenoses Due to Mutation of the Elastin Gene

We present a 3-year-old boy with an elastin gene mutation and multiple peripheral pulmonary stenoses, who developed aneurysms of the pulmonary arteries spontaneously. We performed transcatheter occlusion of the aneurysms with detachable coils. While pulmonary arterial aneurysms may develop following pulmonary balloon angioplasty, spontaneous development is exceedingly rare. To the best of our knowledge, this is the first report describing spontaneous development of pulmonary artery aneurysms in a patient with peripheral pulmonary artery stenoses due to mutation of the elastin gene or Williams–Beuren syndrome.