Flow stagnation volume and abdominal aortic aneurysm growth: Insights from patient-specific computational flow dynamics of Lagrangian-coherent structures.

PubMed

Joly, Florian; Soulez, Gilles; Garcia, Damien; Lessard, Simon; Kauffmann, Claude

2018-01-01

Abdominal aortic aneurysms (AAA) are localized, commonly-occurring dilations of the aorta. When equilibrium between blood pressure (loading) and wall mechanical resistance is lost, rupture ensues, and patient death follows, if not treated immediately. Experimental and numerical analyses of flow patterns in arteries show direct correlations between wall shear stress and wall mechano-adaptation with the development of zones prone to thrombus formation. For further insights into AAA flow topology/growth interaction, a workout of patient-specific computational flow dynamics (CFD) is proposed to compute finite-time Lyapunov exponents and extract Lagrangian-coherent structures (LCS). This computational model was first compared with 4-D phase-contrast magnetic resonance imaging (MRI) in 5 patients. To better understand the impact of flow topology and transport on AAA growth, hyperbolic, repelling LCS were computed in 1 patient during 8-year follow-up, including 9 volumetric morphologic AAA measures by computed tomography-angiography (CTA). LCS defined barriers to Lagrangian jet cores entering AAA. Domains enclosed between LCS and the aortic wall were considered to be stagnation zones. Their evolution was studied during AAA growth. Good correlation - 2-D cross-correlation coefficients of 0.65, 0.86 and 0.082 (min, max, SD) - was obtained between numerical simulations and 4-D MRI acquisitions in 6 specific cross-sections from 4 patients. In follow-up study, LCS divided AAA lumens into 3 dynamically-isolated zones: 2 stagnation volumes lying in dilated portions of the AAA, and circulating volume connecting the inlet to the outlet. The volume of each zone was tracked over time. Although circulating volume remained unchanged during 8-year follow-up, the AAA lumen and main stagnation zones grew significantly (8 cm 3 /year and 6 cm 3 /year, respectively). This study reveals that transient transport topology can be quantified in patient-specific AAA during disease progression by CTA, in parallel with lumen morphology. It is anticipated that analysis of the main AAA stagnation zones by patient-specific CFD on a yearly basis could help to predict AAA growth and rupture. Copyright © 2017 Elsevier Ltd. All rights reserved.

Blood flow and coherent vortices in the normal and aneurysmatic aortas: a fluid dynamical approach to intra-luminal thrombus formation.

PubMed

Biasetti, Jacopo; Hussain, Fazle; Gasser, T Christian

2011-10-07

Abdominal aortic aneurysms (AAAs) are frequently characterized by the development of an intra-luminal thrombus (ILT), which is known to have multiple biochemical and biomechanical implications. Development of the ILT is not well understood, and shear-stress-triggered activation of platelets could be the first step in its evolution. Vortical structures (VSs) in the flow affect platelet dynamics, which motivated the present study of a possible correlation between VS and ILT formation in AAAs. VSs educed by the λ(2)-method using computational fluid dynamics simulations of the backward-facing step problem, normal aorta, fusiform AAA and saccular AAA were investigated. Patient-specific luminal geometries were reconstructed from computed tomography scans, and Newtonian and Carreau-Yasuda models were used to capture salient rheological features of blood flow. Particularly in complex flow domains, results depended on the constitutive model. VSs developed all along the normal aorta, showing that a clear correlation between VSs and high wall shear stress (WSS) existed, and that VSs started to break up during late systole. In contrast, in the fusiform AAA, large VSs developed at sites of tortuous geometry and high WSS, occupying the entire lumen, and lasting over the entire cardiac cycle. Downward motion of VSs in the AAA was in the range of a few centimetres per cardiac cycle, and with a VS burst at that location, the release (from VSs) of shear-stress-activated platelets and their deposition to the wall was within the lower part of the diseased artery, i.e. where the thickest ILT layer is typically observed. In the saccular AAA, only one VS was found near the healthy portion of the aorta, while in the aneurysmatic bulge, no VSs occurred. We present a fluid-dynamics-motivated mechanism for platelet activation, convection and deposition in AAAs that has the potential of improving our current understanding of the pathophysiology of fluid-driven ILT growth.

On the Impact of Intraluminal Thrombus Mechanical Behavior in AAA Passive Mechanics.

PubMed

Riveros, Fabián; Martufi, Giampaolo; Gasser, T Christian; Rodriguez-Matas, Jose F

2015-09-01

Intraluminal thrombus (ILT) is a pseudo-tissue that develops from coagulated blood, and is found in most abdominal aortic aneurysms (AAAs) of clinically relevant size. A number of studies have suggested that ILT mechanical characteristics may be related to AAA risk of rupture, even though there is still great controversy in this regard. ILT is isotropic and inhomogeneous and may appear as a soft (single-layered) or stiff (multilayered fibrotic) tissue. This paper aims to investigate how ILT constitution and topology influence the magnitude and location of peak wall stress (PWS). In total 21 patient-specific AAAs (diameter 4.2-5.4 cm) were reconstructed from computer tomography images and biomechanically analyzed using state-of-the-art modeling assumptions. Results indicated that PWS correlated stronger with ILT volume (ρ = 0.44, p = 0.05) and minimum thickness of ILT layer (ρ = 0.73, p = 0.001) than with maximum AAA diameter (ρ = 0.05, p = 0.82). On average PWS was 20% (SD 12%) higher for FE models that used soft instead of stiff ILT models (p < 0.001). PWS location strongly correlated with sites of minimum ILT thickness in the section of maximum AAA diameter and was independent from ILT stiffness. In addition, ILT heterogeneity, i.e., the spatial composition of soft and stiff thrombus tissue, can considerably influence stress in the AAA wall. The present study is limited to identification of influential biomechanical factors, and how its findings translate to an AAA rupture risk assessment remains to be explored by clinical studies.

Gender, smoking, body size, and aneurysm geometry influence the biomechanical rupture risk of abdominal aortic aneurysms as estimated by finite element analysis.

PubMed

Lindquist Liljeqvist, Moritz; Hultgren, Rebecka; Siika, Antti; Gasser, T Christian; Roy, Joy

2017-04-01

Finite element analysis (FEA) has been suggested to be superior to maximal diameter measurements in predicting rupture of abdominal aortic aneurysms (AAAs). Our objective was to investigate to what extent previously described rupture risk factors were associated with FEA-estimated rupture risk. One hundred forty-six patients with an asymptomatic AAA of a 40- to 60-mm diameter were retrospectively identified and consecutively included. The patients' computed tomography angiograms were analyzed by FEA without (neutral) and with (specific) input of patient-specific mean arterial pressure (MAP), gender, family history, and age. The maximal wall stress/wall strength ratio was described as a rupture risk equivalent diameter (RRED), which translated this ratio into an average aneurysm diameter of corresponding rupture risk. In multivariate linear regression, RRED neutral increased with female gender (3.7 mm; 95% confidence interval [CI], 0.13-7.3) and correlated with patient height (0.27 mm/cm; 95% CI, 0.11-0.43) and body surface area (BSA, 16 mm/m 2 ; 95% CI, 8.3-24) and inversely with body mass index (BMI, -0.40 mm/kg m -2 ; 95% CI, -0.75 to -0.054) in a wall stress-dependent manner. Wall stress-adjusted RRED neutral was raised if the patient was currently smoking (1.1 mm; 95% CI, 0.21-1.9). Age, MAP, family history, and patient weight were unrelated to RRED neutral . In specific FEA, RRED specific increased with female gender, MAP, family history positive for AAA, height, and BSA, whereas it was inversely related to BMI. All results were independent of aneurysm diameter. Peak wall stress and RRED correlated with aneurysm diameter and lumen volume. Female gender, current smoking, increased patient height and BSA, and low BMI were found to increase the mechanical rupture risk of AAAs. Previously described rupture risk factors may in part be explained by patient characteristic-dependent variations in aneurysm biomechanics. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Astragaloside IV Attenuated 3,4-Benzopyrene-Induced Abdominal Aortic Aneurysm by Ameliorating Macrophage-Mediated Inflammation.

PubMed

Wang, Jiaoni; Zhou, Yingying; Wu, Shaoze; Huang, Kaiyu; Thapa, Saroj; Tao, Luyuan; Wang, Jie; Shen, Yigen; Wang, Jinsheng; Xue, Yangjing; Ji, Kangting

2018-01-01

Abdominal aortic aneurysm (AAA), characterized by macrophage infiltration-mediated inflammation and oxidative stress, is a potentially fatal disease. Astragaloside IV (AS-IV) has been acknowledged to exhibit antioxidant and anti-inflammatory properties. This study was designed to investigate the protective effect of AS-IV against AAA formation induced by 3,4-benzopyrene (Bap) and angiotensin II (Ang II), and to explore probable mechanisms. Results showed that AS-IV decreased AAA formation, and reduced macrophage infiltration and expression of matrix metalloproteinase. Furthermore, AS-IV abrogated Bap-/Ang II-induced NF-κB activation and oxidative stress. In vitro , AS-IV inhibition of macrophage activation and NF-κB was correlated with increased phosphorylation of phosphatidylinositol 3-kinase (PI3-K)/AKT. Together, our findings suggest that AS-IV has potential as an intervention in the formation of AAA. (1)The protective effect of Astragaloside IV (AS-IV) on abdominal aortic aneurysm (AAA) is associated with its suppressing effects on inflammation in the aortic wall.(2)AS-IV abrogated 3,4-benzopyrene (Bap)/angiotensin II (Ang II)-induced nuclear factor-κB (NF-κB) activation and oxidative stress.(3)AS-IV inhibited Bap-induced RAW264.7 macrophage cells activation by inhibiting oxidative stress and NF-κB activation through phosphatidylinositol 3-kinase (PI3-K)/AKT pathway.AS-IV is a potential preventive agent for cigarette smoking-related AAA.

Overexpression of Catalase in Vascular Smooth Muscle Cells Prevents the Formation of Abdominal Aortic Aneurysms

PubMed Central

Parastatidis, Ioannis; Weiss, Daiana; Joseph, Giji; Taylor, W Robert

2013-01-01

Objective Elevated levels of oxidative stress have been reported in abdominal aortic aneurysms (AAA), but which reactive oxygen species (ROS) promotes the development of AAA remains unclear. Here we investigate the effect of the hydrogen peroxide (H2O2) degrading enzyme catalase on the formation of AAA. Approach and Results AAA were induced with the application of calcium chloride (CaCl2) on mouse infrarenal aortas. The administration of PEG-catalase, but not saline, attenuated the loss of tunica media and protected against AAA formation (0.91±0.1 mm vs. 0.76±0.09 mm). Similarly, in a transgenic mouse model, catalase over-expression in the vascular smooth muscle cells (VSMC) preserved the thickness of tunica media and inhibited aortic dilatation by 50% (0.85±0.14 mm vs. 0.57±0.08 mm). Further studies showed that injury with CaCl2 decreased catalase expression and activity in the aortic wall. Pharmacologic administration or genetic over-expression of catalase restored catalase activity and subsequently decreased matrix metalloproteinase activity. In addition, a profound reduction in inflammatory markers and VSMC apoptosis was evident in aortas of catalase over-expressing mice. Interestingly, as opposed to infusion of PEG-catalase, chronic over-expression of catalase in VSMC did not alter the total aortic H2O2 levels. Conclusions The data suggest that a reduction in aortic wall catalase activity can predispose to AAA formation. Restoration of catalase activity in the vascular wall enhances aortic VSMC survival and prevents AAA formation primarily through modulation of matrix metalloproteinase activity. PMID:23950141

Histology and Biaxial Mechanical Behavior of Abdominal Aortic Aneurysm Tissue Samples.

PubMed

Pancheri, Francesco Q; Peattie, Robert A; Reddy, Nithin D; Ahamed, Touhid; Lin, Wenjian; Ouellette, Timothy D; Iafrati, Mark D; Luis Dorfmann, A

2017-03-01

Abdominal aortic aneurysms (AAAs) represent permanent, localized dilations of the abdominal aorta that can be life-threatening if progressing to rupture. Evaluation of risk of rupture depends on understanding the mechanical behavior of patient AAA walls. In this project, a series of patient AAA wall tissue samples have been evaluated through a combined anamnestic, mechanical, and histopathologic approach. Mechanical properties of the samples have been characterized using a novel, strain-controlled, planar biaxial testing protocol emulating the in vivo deformation of the aorta. Histologically, the tissue ultrastructure was highly disrupted. All samples showed pronounced mechanical stiffening with stretch and were notably anisotropic, with greater stiffness in the circumferential than the axial direction. However, there were significant intrapatient variations in wall stiffness and stress. In biaxial tests in which the longitudinal stretch was held constant at 1.1 as the circumferential stretch was extended to 1.1, the maximum average circumferential stress was 330 ± 70 kPa, while the maximum average axial stress was 190 ± 30 kPa. A constitutive model considering the wall as anisotropic with two preferred directions fit the measured data well. No statistically significant differences in tissue mechanical properties were found based on patient gender, age, maximum bulge diameter, height, weight, body mass index, or smoking history. Although a larger patient cohort is merited to confirm these conclusions, the project provides new insight into the relationships between patient natural history, histopathology, and mechanical behavior that may be useful in the development of accurate methods for rupture risk evaluation.

Characterization of the mechanical behavior and pathophysiological state of abdominal aortic aneurysms based on 4D ultrasound strain imaging

NASA Astrophysics Data System (ADS)

Wittek, Andreas; Blase, Christopher; Derwich, Wojciech; Schmitz-Rixen, Thomas; Fritzen, Claus-Peter

2017-06-01

Abdominal aortic aneurysms (AAA) are a degenerative disease of the human aortic wall that may lead to weakening and eventually rupture of the wall with high mortality rates. Since the currently established criterion for surgical or endovascular treatment of the disease is imprecise in the individual case and treatment is not free of complications, the need for additional patient-individual biomarkers for short-term AAA rupture risk as basis for improved clinical decision making. Time resolved 3D ultrasound combined with speckle tracking algorithms is a novel non-invasive medical imaging technique that provides full-field displacement and strain measurements of aortic and aneurysmal wall motion. This is patient-individual information that has not been used so far to assess wall strength and rupture risk. The current study uses simple statistical indices of the heterogeneous spatial distribution of in-plane strain components as biomarkers for the pathological state of the aortic and aneurysmal wall. The pathophysiological rationale behind this approach are the known changes in microstructural composition of the aortic wall with progression of AAA development that results in increased stiffening and heterogeneity of the walls mechanical properties and in decreased wall strength. In a comparative analysis of the aortic wall motion of young volunteers without known cardiovascular diseases, aged arteriosclerotic patients without AAA, and AAA patients, mean values of all in-plane strain components were significantly reduced, and the heterogeneity of circumferential strain was significantly increased in the AAA group compared to both other groups. The capacity of the proposed method to differentiate between wall motion of aged, arteriosclerotic patients and AAA patients is a promising step towards a new method for in vivo assessment of AAA wall strength or stratification of AAA rupture risk as basis for improved clinical decision making on surgical or endovascular treatment of AAA.

Turbulence significantly increases pressure and fluid shear stress in an aortic aneurysm model under resting and exercise flow conditions.

PubMed

Khanafer, Khalil M; Bull, Joseph L; Upchurch, Gilbert R; Berguer, Ramon

2007-01-01

The numerical models of abdominal aortic aneurysm (AAA) in use do not take into account the non-Newtonian behavior of blood and the development of local turbulence. This study examines the influence of pulsatile, turbulent, non-Newtonian flow on fluid shear stresses and pressure changes under rest and exercise conditions. We numerically analyzed pulsatile turbulent flow, using simulated physiological rest and exercise waveforms, in axisymmetric-rigid aortic aneurysm models (AAMs). Discretization of governing equations was achieved using a finite element scheme. Maximum turbulence-induced shear stress was found at the distal end of an AAM. In large AAMs (dilated to undilated diameter ratio = 3.33) at peak systolic flow velocity, fluid shear stress during exercise is 70.4% higher than at rest. Our study provides a numerical, noninvasive method for obtaining detailed data on the forces generated by pulsatile turbulent flow in AAAs that are difficult to study in humans and in physical models. Our data suggest that increased flow turbulence results in increased shear stress in aneurysms. While pressure readings are fairly uniform along the length of an aneurysm, the kinetic energy generated by turbulence impacting on the wall of the distal half of the aneurysm increases fluid and wall shear stress at this site. If the increased fluid shear stress results in further dilation and hence further turbulence, wall stress may be a mechanism for aneurysmal growth and eventual rupture.

3D-Printed Tissue-Mimicking Phantoms for Medical Imaging and Computational Validation Applications

PubMed Central

Shahmirzadi, Danial; Li, Ronny X.; Doyle, Barry J.; Konofagou, Elisa E.; McGloughlin, Tim M.

2014-01-01

Abstract Abdominal aortic aneurysm (AAA) is a permanent, irreversible dilation of the distal region of the aorta. Recent efforts have focused on improved AAA screening and biomechanics-based failure prediction. Idealized and patient-specific AAA phantoms are often employed to validate numerical models and imaging modalities. To produce such phantoms, the investment casting process is frequently used, reconstructing the 3D vessel geometry from computed tomography patient scans. In this study the alternative use of 3D printing to produce phantoms is investigated. The mechanical properties of flexible 3D-printed materials are benchmarked against proven elastomers. We demonstrate the utility of this process with particular application to the emerging imaging modality of ultrasound-based pulse wave imaging, a noninvasive diagnostic methodology being developed to obtain regional vascular wall stiffness properties, differentiating normal and pathologic tissue in vivo. Phantom wall displacements under pulsatile loading conditions were observed, showing good correlation to fluid–structure interaction simulations and regions of peak wall stress predicted by finite element analysis. 3D-printed phantoms show a strong potential to improve medical imaging and computational analysis, potentially helping bridge the gap between experimental and clinical diagnostic tools. PMID:28804733

On the effect of computed tomography resolution to distinguish between abdominal aortic aneurysm wall tissue and calcification: A proof of concept.

PubMed

Barrett, H E; Cunnane, E M; O Brien, J M; Moloney, M A; Kavanagh, E G; Walsh, M T

2017-10-01

The purpose of this study is to determine the optimal target CT spatial resolution for accurately imaging abdominal aortic aneurysm (AAA) wall characteristics, distinguishing between tissue and calcification components, for an accurate assessment of rupture risk. Ruptured and non-ruptured AAA-wall samples were acquired from eight patients undergoing open surgical aneurysm repair upon institutional review board approval and informed consent was obtained from all patients. Physical measurements of AAA-wall cross-section were made using scanning electron microscopy. Samples were scanned using high resolution micro-CT scanning. A resolution range of 15.5-155μm was used to quantify the influence of decreasing resolution on wall area measurements, in terms of tissue and calcification. A statistical comparison between the reference resolution (15.5μm) and multi-detector CT resolution (744μm) was also made. Electron microscopy examination of ruptured AAAs revealed extremely thin outer tissue structure <200μm in radial distribution which is supporting the aneurysm wall along with large areas of adjacent medial calcifications far greater in area than the tissue layer. The spatial resolution of 155μm is a significant predictor of the reference AAA-wall tissue and calcification area measurements (r=0.850; p<0.001; r=0.999; p<0.001 respectively). The tissue and calcification area at 155μm is correct within 8.8%±1.86 and 26.13%±9.40 respectively with sensitivity of 87.17% when compared to the reference. The inclusion of AAA-wall measurements, through the use of high resolution-CT will elucidate the variations in AAA-wall tissue and calcification distributions across the wall which may help to leverage an improved assessment of AAA rupture risk. Copyright © 2017 Elsevier B.V. All rights reserved.

Adipocytes and abdominal aortic aneurysm: Putative potential role of adipocytes in the process of AAA development.

PubMed

Kugo, Hirona; Moriyama, Tatsuya; Zaima, Nobuhiro

2018-01-15

Background Adipose tissue plays a role in the storage of excess energy as triglycerides (TGs). Excess fat accumulation causes various metabolic and cardiovascular diseases. It has been reported that ectopic fat deposition and excess TG accumulation in non-adipose tissue might be important predictors of cardiometabolic and vascular risk. For example, ectopic fat in perivascular tissue promotes atherosclerotic plaque formation in the arterial wall. Objective Recently, it has been reported that ectopic fat (adipocyte) in the vascular wall of an abdominal aortic aneurysm (AAA) is present in both human and experimental animal models. The pathological significance of adipocytes in the AAA wall has not been fully understood. In this review, we summarized the functions of adipocytes and discussed potential new drugs that target vascular adipocytes for AAA treatment. Result Previous studies suggest that adipocytes in vascular wall play an important role in the development of AAA. Conclusion Adipocytes in the vascular wall could be novel targets for the development of AAA therapeutic drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Understanding the pathogenesis of abdominal aortic aneurysms

PubMed Central

Kuivaniemi, Helena; Ryer, Evan J.; Elmore, James R.; Tromp, Gerard

2016-01-01

Summary An aortic aneurysm is a dilatation in which the aortic diameter is ≥ 3.0 cm. If left untreated, the aortic wall continues to weaken and becomes unable to withstand the forces of the luminal blood pressure resulting in progressive dilatation and rupture, a catastrophic event associated with a mortality of 50 – 80%. Smoking and positive family history are important risk factors for the development of abdominal aortic aneurysms (AAA). Several genetic risk factors have also been identified. On the histological level, visible hallmarks of AAA pathogenesis include inflammation, smooth muscle cell apoptosis, extracellular matrix degradation, and oxidative stress. We expect that large genetic, genomic, epigenetic, proteomic and metabolomic studies will be undertaken by international consortia to identify additional risk factors and biomarkers, and to enhance our understanding of the pathobiology of AAA. Collaboration between different research groups will be important in overcoming the challenges to develop pharmacological treatments for AAA. PMID:26308600

CXCL8 hyper-signaling in the aortic abdominal aneurysm.

PubMed

Kokje, Vivianne B C; Gäbel, Gabor; Dalman, Ron L; Koole, Dave; Northoff, Bernd H; Holdt, Lesca M; Hamming, Jaap F; Lindeman, Jan H N

2018-08-01

There are indications for elevated CXCL8 levels in abdominal aortic aneurysm disease (AAA). CXCL8 is concurrently involved in neutrophil-mediated inflammation and angiogenesis, two prominent and distinctive characteristics of AAA. As such we considered an evaluation of a role for CXCL8 in AAA progression relevant. ELISA's, real time PCR and array analysis were used to explore CXCL8 signaling in AAA wall samples. A role for CXCL8 in AAA disease was tested through the oral CXCR1/2 antagonist DF2156A in the elastase model of AAA disease. There is an extreme disparity in aortic wall CXCL8 content between AAA and aortic atherosclerotic disease (median [IQR] aortic wall CXCL8 content: 425 [141-1261] (AAA) vs. 23 [2.8-89] (atherosclerotic aorta) µg/g protein (P < 1 · 10 -14 )), and abundant expression of the CXCR1 and 2 receptors in AAA. Array analysis followed by pathway analysis showed that CXCL8 hyper-expression in AAA is followed increased by IL-8 signaling (Z-score for AAA vs. atherosclerotic control: 2.97, p < 0.0001). Interference with CXCL8 signaling through DF2156A fully abrogated AAA formation and prevented matrix degradation in the murine elastase model of AAA disease (p < 0.001). CXCL8-signaling is a prominent and distinctive feature of AAA, interference with the pathway constitutes a promising target for medical stabilization of AAA. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Effect of aorto-iliac bifurcation and iliac stenosis on flow dynamics in an abdominal aortic aneurysm

NASA Astrophysics Data System (ADS)

Patel, Shivam; Usmani, Abdullah Y.; Muralidhar, K.

2017-06-01

Physiological flows in rigid diseased arterial flow phantoms emulating an abdominal aortic aneurysm (AAA) under rest conditions with aorto-iliac bifurcation and iliac stenosis are examined in vitro through 2D PIV measurements. Flow characteristics are first established in the model resembling a symmetric AAA with a straight outlet tube. The influence of aorto-iliac bifurcation and iliac stenosis on AAA flow dynamics is then explored through a comparison of the nature of flow patterns, vorticity evolution, vortex core trajectory and hemodynamic factors against the reference configuration. Specifically, wall shear stress and oscillatory shear index in the bulge portion of the models are of interest. The results of this investigation indicate overall phenomenological similarity in AAA flow patterns across the models. The pattern is characterized by a central jet and wall-bounded vortices whose strength increases during the deceleration phase as it moves forward. The central jet impacts the wall of AAA at its distal end. In the presence of an aorto-iliac bifurcation as well as iliac stenosis, the flow patterns show diminished strength, expanse and speed of propagation of the primary vortices. The positions of the instantaneous vortex cores, determined using the Q-function, correlate with flow separation in the bulge, flow resistance due to a bifurcation, and the break in symmetry introduced by a stenosis in one of the legs of the model. Time-averaged WSS in a healthy aorta is around 0.70 N m-2 and is lowered to the range ±0.2 N m-2 in the presence of the downstream bifurcation with a stenosed common iliac artery. The consequence of changes in the flow pattern within the aneurysm on disease progression is discussed.

The Relationship Between Pulsatile Flow Impingement and Intraluminal Thrombus Deposition in Abdominal Aortic Aneurysms.

PubMed

Lozowy, Richard J; Kuhn, David C S; Ducas, Annie A; Boyd, April J

2017-03-01

Direct numerical simulations were performed on four patient-specific abdominal aortic aneurysm (AAA) geometries and the resulting pulsatile blood flow dynamics were compared to aneurysm shape and correlated with intraluminal thrombus (ILT) deposition. For three of the cases, turbulent vortex structures impinged/sheared along the anterior wall and along the posterior wall a zone of recirculating blood formed. Within the impingement region the AAA wall was devoid of ILT and remote to this region there was an accumulation of ILT. The high wall shear stress (WSS) caused by the impact of vortexes is thought to prevent the attachment of ILT. WSS from impingement is comparable to peak-systolic WSS in a normal-sized aorta and therefore may not damage the wall. Expansion occurred to a greater extent in the direction of jet impingement and the wall-normal force from the continuous impact of vortexes may contribute to expansion. It was shown that the impingement region has low oscillatory shear index (OSI) and recirculation zones can have either low or high OSI. No correlation could be identified between OSI and ILT deposition since different flow dynamics can have similar OSI values.

A numerical framework for studying the biomechanical behavior of abdominal aortic aneurysm

NASA Astrophysics Data System (ADS)

Jalalahmadi, Golnaz; Linte, Cristian; Helguera, María.

2017-03-01

Abdominal aortic aneurysm (AAA) is known as a leading cause of death in the United States. AAA is an abnormal dilation of the aorta, which usually occurs below the renal arteries and causes an expansion at least 1.5 times its normal diameter. It has been shown that biomechanical parameters of the aortic tissue coupled with a set of specific geometric parameters characterizing the vessel expansion, affect the risk of aneurysm rupture. Here, we developed a numerical framework that incorporates both biomechanical and geometrical factors to study the behavior of abdominal aortic aneurysm. Our workflow enables the extraction of the aneurysm geometry from both clinical quality, as well as low-resolution MR images. We used a two-parameter, hyper-elastic, isotropic, incompressible material to model the vessel tissue. Our numerical model was tested using both synthetic and mouse data and we evaluated the effects of the geometrical and biomechanical properties on the developed peak wall stress. In addition, we performed several parameter sensitivity studies to investigate the effect of different factors affecting the AAA and its behavior and rupture. Lastly, relationships between different geometrical and biomechanical parameters and peak wall stress were determined. These studies help us better understand vessel tissue response to various loading, geometry and biomechanics conditions, and we plan to further correlate these findings with the pathophysiological conditions from a patient population diagnosed with abdominal aortic aneurysms.

A two-system, single-analysis, fluid-structure interaction technique for modelling abdominal aortic aneurysms.

PubMed

Kelly, S C; O'Rourke, M J

2010-01-01

This work reports on the implementation and validation of a two-system, single-analysis, fluid-structure interaction (FSI) technique that uses the finite volume (FV) method for performing simulations on abdominal aortic aneurysm (AAA) geometries. This FSI technique, which was implemented in OpenFOAM, included fluid and solid mesh motion and incorporated a non-linear material model to represent AAA tissue. Fully implicit coupling was implemented, ensuring that both the fluid and solid domains reached convergence within each time step. The fluid and solid parts of the FSI code were validated independently through comparison with experimental data, before performing a complete FSI simulation on an idealized AAA geometry. Results from the FSI simulation showed that a vortex formed at the proximal end of the aneurysm during systolic acceleration, and moved towards the distal end of the aneurysm during diastole. Wall shear stress (WSS) values were found to peak at both the proximal and distal ends of the aneurysm and remain low along the centre of the aneurysm. The maximum von Mises stress in the aneurysm wall was found to be 408kPa, and this occurred at the proximal end of the aneurysm, while the maximum displacement of 2.31 mm occurred in the centre of the aneurysm. These results were found to be consistent with results from other FSI studies in the literature.

Improving the Efficiency of Abdominal Aortic Aneurysm Wall Stress Computations

PubMed Central

Zelaya, Jaime E.; Goenezen, Sevan; Dargon, Phong T.; Azarbal, Amir-Farzin; Rugonyi, Sandra

2014-01-01

An abdominal aortic aneurysm is a pathological dilation of the abdominal aorta, which carries a high mortality rate if ruptured. The most commonly used surrogate marker of rupture risk is the maximal transverse diameter of the aneurysm. More recent studies suggest that wall stress from models of patient-specific aneurysm geometries extracted, for instance, from computed tomography images may be a more accurate predictor of rupture risk and an important factor in AAA size progression. However, quantification of wall stress is typically computationally intensive and time-consuming, mainly due to the nonlinear mechanical behavior of the abdominal aortic aneurysm walls. These difficulties have limited the potential of computational models in clinical practice. To facilitate computation of wall stresses, we propose to use a linear approach that ensures equilibrium of wall stresses in the aneurysms. This proposed linear model approach is easy to implement and eliminates the burden of nonlinear computations. To assess the accuracy of our proposed approach to compute wall stresses, results from idealized and patient-specific model simulations were compared to those obtained using conventional approaches and to those of a hypothetical, reference abdominal aortic aneurysm model. For the reference model, wall mechanical properties and the initial unloaded and unstressed configuration were assumed to be known, and the resulting wall stresses were used as reference for comparison. Our proposed linear approach accurately approximates wall stresses for varying model geometries and wall material properties. Our findings suggest that the proposed linear approach could be used as an effective, efficient, easy-to-use clinical tool to estimate patient-specific wall stresses. PMID:25007052

Histopathological analysis of cellular localization of cathepsins in abdominal aortic aneurysm wall.

PubMed

Lohoefer, Fabian; Reeps, Christian; Lipp, Christina; Rudelius, Martina; Zimmermann, Alexander; Ockert, Stefan; Eckstein, Hans-Henning; Pelisek, Jaroslav

2012-08-01

An important feature of abdominal aortic aneurysm (AAA) is the destruction of vessel wall, especially elastin and collagen. Besides matrix metalloproteinases, cathepsins are the most potent elastolytic enzymes. The expression of cathepsins with known elastolytic and collagenolytic activities in the individual cells within AAA has not yet been determined. The vessel wall of 32 AAA patients and 10 organ donors was analysed by immunohistochemistry for expression of cathepsins B, D, K, L and S, and cystatin C in all cells localized within AAA. Luminal endothelial cells (ECs) of AAA were positive for cathepsin D and partially for cathepsins B, K and S. Endothelial cells of the neovessels and smooth muscle cells in the media were positive for all cathepsins tested, especially for cathepsin B. In the inflammatory infiltrate all cathepsins were expressed in the following pattern: B > D = S > K = L. Macrophages showed the highest staining intensity for all cathepsins. Furthermore, weak overall expression of cystatin C was observed in all the cells localized in the AAA with the exception of the ECs. There is markedly increased expression of the various cathepsins within the AAA wall compared to healthy aorta. Our data are broadly consistent with a role for cathepsins in AAA; and demonstrate expression of cathepsins D, B and S in phagocytic cells in the inflammatory infiltrate; and also may reveal a role for cathepsin B in lymphocytes. © 2012 The Authors. International Journal of Experimental Pathology © 2012 International Journal of Experimental Pathology.

Two C-C Family Chemokines, Eotaxin and RANTES, Are Novel Independent Plasma Biomarkers for Abdominal Aortic Aneurysm.

PubMed

Jones, Gregory T; Phillips, L Victoria; Williams, Michael J A; van Rij, Andre M; Kabir, Tasnuva D

2016-04-28

Inflammation of the aortic wall is recognised as a key pathogenesis of abdominal aortic aneurysm (AAA). This study was undertaken to determine whether inflammatory cytokines could be used as biomarkers for the presence of AAA. Tissue profiles of 27 inflammatory cytokine were examined in AAA (n=14) and nonaneurysmal (n=14) aortic tissues. Three cytokines, regulated upon activation normally T-cell expressed and secreted (RANTES), eotaxin, and macrophage inflammatory protein 1 beta (MIP-1b), had increased expression in AAA, particularly within the adventitial layer of the aortic wall. Basic fibroblast growth factor (bFGF) had reduced expression in all layers of the AAA wall. Examination of the circulating plasma profiles of AAA (n=442) and AAA-free controls (n=970) suggested a (risk factor adjusted) AAA-association with eotaxin, RANTES, and high sensitivity C-reactive protein (hsCRP). A plasma inflammatory cytokine score, calculated using these three markers, suggested a strong risk association with AAA (odds ratio, 4.8; 95% CI, 3.5-6.7; P<0.0001), independent of age, sex, history of ischemic heart disease, and smoking. Contrary to reports suggesting a distinct T helper 2-associated inflammatory profile in AAA, this current study suggests a more-generalized pattern of inflammation, albeit with some potentially distinct features, including elevated plasma eotaxin and decreased plasma RANTES. In combination with hsCRP, these markers may have potential utility as AAA biomarkers. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

A novel strategy to translate the biomechanical rupture risk of abdominal aortic aneurysms to their equivalent diameter risk: method and retrospective validation.

PubMed

Gasser, T C; Nchimi, A; Swedenborg, J; Roy, J; Sakalihasan, N; Böckler, D; Hyhlik-Dürr, A

2014-03-01

To translate the individual abdominal aortic aneurysm (AAA) patient's biomechanical rupture risk profile to risk-equivalent diameters, and to retrospectively test their predictability in ruptured and non-ruptured aneurysms. Biomechanical parameters of ruptured and non-ruptured AAAs were retrospectively evaluated in a multicenter study. General patient data and high resolution computer tomography angiography (CTA) images from 203 non-ruptured and 40 ruptured aneurysmal infrarenal aortas. Three-dimensional AAA geometries were semi-automatically derived from CTA images. Finite element (FE) models were used to predict peak wall stress (PWS) and peak wall rupture index (PWRI) according to the individual anatomy, gender, blood pressure, intra-luminal thrombus (ILT) morphology, and relative aneurysm expansion. Average PWS diameter and PWRI diameter responses were evaluated, which allowed for the PWS equivalent and PWRI equivalent diameters for any individual aneurysm to be defined. PWS increased linearly and PWRI exponentially with respect to maximum AAA diameter. A size-adjusted analysis showed that PWS equivalent and PWRI equivalent diameters were increased by 7.5 mm (p = .013) and 14.0 mm (p < .001) in ruptured cases when compared to non-ruptured controls, respectively. In non-ruptured cases the PWRI equivalent diameters were increased by 13.2 mm (p < .001) in females when compared with males. Biomechanical parameters like PWS and PWRI allow for a highly individualized analysis by integrating factors that influence the risk of AAA rupture like geometry (degree of asymmetry, ILT morphology, etc.) and patient characteristics (gender, family history, blood pressure, etc.). PWRI and the reported annual risk of rupture increase similarly with the diameter. PWRI equivalent diameter expresses the PWRI through the diameter of the average AAA that has the same PWRI, i.e. is at the same biomechanical risk of rupture. Consequently, PWRI equivalent diameter facilitates a straightforward interpretation of biomechanical analysis and connects to diameter-based guidelines for AAA repair indication. PWRI equivalent diameter reflects an additional diagnostic parameter that may provide more accurate clinical data for AAA repair indication. Copyright © 2013 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

TGFβ (Transforming Growth Factor-β) Blockade Induces a Human-Like Disease in a Nondissecting Mouse Model of Abdominal Aortic Aneurysm.

PubMed

Lareyre, Fabien; Clément, Marc; Raffort, Juliette; Pohlod, Stefanie; Patel, Meghana; Esposito, Bruno; Master, Leanne; Finigan, Alison; Vandestienne, Marie; Stergiopulos, Nikolaos; Taleb, Soraya; Trachet, Bram; Mallat, Ziad

2017-11-01

Current experimental models of abdominal aortic aneurysm (AAA) do not accurately reproduce the major features of human AAA. We hypothesized that blockade of TGFβ (transforming growth factor-β) activity-a guardian of vascular integrity and immune homeostasis-would impair vascular healing in models of nondissecting AAA and would lead to sustained aneurysmal growth until rupture. Here, we test this hypothesis in the elastase-induced AAA model in mice. We analyze AAA development and progression using ultrasound in vivo, synchrotron-based ultrahigh resolution imaging ex vivo, and a combination of biological, histological, and flow cytometry-based cellular and molecular approaches in vitro. Systemic blockade of TGFβ using a monoclonal antibody induces a transition from a self-contained aortic dilatation to a model of sustained aneurysmal growth, associated with the formation of an intraluminal thrombus. AAA growth is associated with wall disruption but no medial dissection and culminates in fatal transmural aortic wall rupture. TGFβ blockade enhances leukocyte infiltration both in the aortic wall and the intraluminal thrombus and aggravates extracellular matrix degradation. Early blockade of IL-1β or monocyte-dependent responses substantially limits AAA severity. However, blockade of IL-1β after disease initiation has no effect on AAA progression to rupture. Endogenous TGFβ activity is required for the healing of AAA. TGFβ blockade may be harnessed to generate new models of AAA with better relevance to the human disease. We expect that the new models will improve our understanding of the pathophysiology of AAA and will be useful in the identification of new therapeutic targets. © 2017 American Heart Association, Inc.

Locally applied leptin induces regional aortic wall degeneration preceding aneurysm formation in apolipoprotein E-deficient mice.

PubMed

Tao, Ming; Yu, Peng; Nguyen, Binh T; Mizrahi, Boaz; Savion, Naphtali; Kolodgie, Frank D; Virmani, Renu; Hao, Shuai; Ozaki, C Keith; Schneiderman, Jacob

2013-02-01

Leptin promotes atherosclerosis and vessel wall remodeling. As abdominal aortic aneurysm (AAA) formation involves tissue remodeling, we hypothesized that local leptin synthesis initiates and promotes this process. Human surgical AAA walls were analyzed for antigen and mRNA levels of leptin and leptin receptor, as well as mRNA for matrix metalloproteinases (MMP)-9 and MMP-12. Leptin and leptin receptor antigen were evident in all AAAs, and leptin, MMP-9, and MMP-12 mRNA was increased relative to age-matched nondilated controls. To simulate in vivo local leptin synthesis, ApoE(-/-) mice were subjected to a paravisceral periaortic application of low-dose leptin. Leptin-treated aortas exhibited decreased transforming growth factor-β and increased MMP-9 mRNA levels 5 days after surgery, and leptin receptor mRNA was upregulated by day 28. Serial ultrasonography demonstrated accelerated regional aortic diameter growth after 28 days, correlating with local medial degeneration, increased MMP-9, MMP-12, and periadventitial macrophage clustering. Furthermore, the combination of local periaortic leptin and systemic angiotensin II administration augmented medial MMP-9 synthesis and aortic aneurysm size. Leptin is locally synthesized in human AAA wall. Paravisceral aortic leptin in ApoE(-/-) mice induces local medial degeneration and augments angiotensin II-induced AAA, thus suggesting novel mechanistic links between leptin and AAA formation.

Locally Applied Leptin Induces Regional Aortic Wall Degeneration Preceding Aneurysm Formation in ApoE Deficient Mice

PubMed Central

Tao, Ming; Yu, Peng; Nguyen, Binh T.; Mizrahi, Boaz; Savion, Naphtali; Kolodgie, Frank D.; Virmani, Renu; Hao, Shuai; Ozaki, C. Keith; Schneiderman, Jacob

2013-01-01

Objective Leptin promotes atherosclerosis and vessel wall remodeling. As abdominal aorta aneurysm (AAA) formation involves tissue remodeling, we hypothesized that local leptin synthesis initiates and promotes this process. Methods and Results Human surgical AAA walls were analyzed for antigen and mRNA levels of leptin and leptin receptor (ObR), as well as mRNA for matrix metalloproteinases (MMP)-9, and MMP-12. Leptin and ObR antigen were evident in all AAAs, and, leptin, MMP-9, and MMP-12 mRNA was increased relative to age-matched non-dilated controls. To simulate in vivo local leptin synthesis, ApoE-/- mice were subjected to a para-visceral peri-aortic application of low-dose leptin. Leptin-treated aortas exhibited decreased TGFβ and increased MMP-9 mRNA levels 5 days after surgery, and ObR mRNA was up-regulated by day 28. Serial ultrasonography demonstrated accelerated regional aortic diameter growth after 28 days, correlating with local medial degeneration, increased MMP-9, MMP-12 and peri-adventitial macrophage clustering. Furthermore, the combination of local peri-aortic leptin and systemic angiotensin II administration augmented medial MMP-9 synthesis and aortic aneurysm size. Conclusions Leptin is locally synthesized in human AAA wall. Para-visceral aortic leptin in ApoE-/- mice induces local medial degeneration, and augments angiotensin II-induced AAA, thus suggesting novel mechanistic links between leptin and AAA formation. PMID:23220275

Adventitial adipogenic degeneration is an unidentified contributor to aortic wall weakening in the abdominal aortic aneurysm.

PubMed

Doderer, Stefan A; Gäbel, Gabor; Kokje, Vivianne B C; Northoff, Bernd H; Holdt, Lesca M; Hamming, Jaap F; Lindeman, Jan H N

2018-06-01

The processes driving human abdominal aortic aneurysm (AAA) progression are not fully understood. Although antiinflammatory and proteolytic strategies effectively quench aneurysm progression in preclinical models, so far all clinical interventions failed. These observations hint at an incomplete understanding of the processes involved in AAA progression and rupture. Interestingly, strong clinical and molecular associations exist between popliteal artery aneurysms (PAAs) and AAAs; however, PAAs have an extremely low propensity to rupture. We thus reasoned that differences between these aneurysms may provide clues toward (auxiliary) processes involved in AAA-related wall debilitation. A better understanding of the pathophysiologic processes driving AAA growth can contribute to pharmaceutical treatments in the future. Aneurysmal wall samples were collected during open elective and emergency repair. Control perirenal aorta was obtained during kidney transplantation, and reference popliteal tissue obtained from the anatomy department. This study incorporates various techniques including (immuno)histochemistry, Western Blot, quantitative polymerase chain reaction, microarray, and cell culture. Histologic evaluation of AAAs, PAAs, and control aorta shows extensive medial (PAA) and transmural fibrosis (AAA), and reveals abundant adventitial adipocytes aggregates as an exclusive phenomenon of AAAs (P < .001). Quantitative polymerase chain reaction, immunohistochemistry, Western blotting, and microarray analysis showed enrichment of adipogenic mediators (C/EBP family P = .027; KLF5 P < .000; and peroxisome proliferator activated receptor-γ, P = .032) in AAA tissue. In vitro differentiation tests indicated a sharply increased adipogenic potential of AAA adventitial mesenchymal cells (P < .0001). Observed enrichment of adipocyte-related genes and pathways in ruptured AAA (P < .0003) supports an association between the extent of fatty degeneration and rupture. This translational study identifies extensive adventitial fatty degeneration as an ignored and distinctive feature of AAA disease. Enrichment of adipocyte genesis and adipocyte-related genes in ruptured AAA point to an association between the extent of fatty degeneration and rupture. This observation may (partly) explain the failure of medical therapy and could provide a lead for pharmaceutical alleviation of AAA progression. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun Zhonghua, E-mail: z.sun@curtin.edu.a; Chaichana, Thanapong

The purpose of the study was to investigate the hemodynamic effect of stent struts (wires) on renal arteries in patients with abdominal aortic aneurysms (AAAs) treated with suprarenal stent-grafts. Two sample patients with AAA undergoing multislice CT angiography pre- and postsuprarenal fixation of stent-grafts were selected for inclusion in the study. Eight juxtarenal models focusing on the renal arteries were generated from the multislice CT datasets. Four types of configurations of stent wires crossing the renal artery ostium were simulated in the segmented aorta models: a single wire crossing centrally, a single wire crossing peripherally, a V-shaped wire crossing centrally,more » and multiple wires crossing peripherally. The blood flow pattern, flow velocity, wall pressure, and wall shear stress at the renal arteries pre- and post-stent-grafting were analyzed and compared using a two-way fluid structure interaction analysis. The stent wire thickness was simulated with a diameter of 0.4, 1.0, and 2.0 mm, and hemodynamic analysis was performed at different cardiac cycles. The interference of stent wires with renal blood flow was mainly determined by the thickness of stent wires and the type of configuration of stent wires crossing the renal ostium. The flow velocity was reduced by 20-30% in most of the situations when the stent wire thickness increased to 1.0 and 2.0 mm. Of the four types of configuration, the single wire crossing centrally resulted in the highest reduction of flow velocity, ranging from 21% to 28.9% among three different wire thicknesses. Wall shear stress was also dependent on the wire thickness, which decreased significantly when the wire thickness reached 1.0 and 2.0 mm. In conclusion, our preliminary study showed that the hemodynamic effect of suprarenal stent wires in patients with AAA treated with suprarenal stent-grafts was determined by the thickness of suprarenal stent wires. Research findings in our study are useful for follow-up of patients treated with suprarenal stent-grafts to ensure long-term safety of the suprarenal fixation.« less

In vivo assessment of aortic aneurysm wall integrity using elastin-specific molecular magnetic resonance imaging.

PubMed

Botnar, René M; Wiethoff, Andrea J; Ebersberger, Ullrich; Lacerda, Sara; Blume, Ulrike; Warley, Alice; Jansen, Christian H P; Onthank, David C; Cesati, Richard R; Razavi, Reza; Marber, Michael S; Hamm, Bernd; Schaeffter, Tobias; Robinson, Simon P; Makowski, Marcus R

2014-07-01

The incidence of abdominal aortic aneurysms (AAAs) has increased during the last decades. However, there is still controversy about the management of medium-sized AAAs. Therefore, novel biomarkers, besides aneurysmal diameter, are needed to assess aortic wall integrity and risk of rupture. Elastin is the key protein for maintaining aortic wall tensile strength and stability. The progressive breakdown of structural proteins, in particular, medial elastin, is responsible for the inability of the aortic wall to withstand intraluminal hemodynamic forces. Here, we evaluate the usefulness of elastin-specific molecular MRI for the in vivo characterization of AAAs. To induce AAAs, ApoE(-/-) mice were infused with angiotensin-II. An elastin-specific magnetic resonance molecular imaging agent (ESMA) was administered after 1, 2, 3, and 4 weeks of angiotensin-II infusion to assess elastin composition of the aorta (n=8 per group). The high signal provided by ESMA allowed for imaging with high spatial resolution, resulting in an accurate assessment of ruptured elastic laminae and the compensatory expression of elastic fibers. In vivo contrast-to-noise ratios and R1-relaxation rates after ESMA administration were in good agreement with ex vivo histomorphometry (Elastica van Gieson stain) and gadolinium concentrations determined by inductively coupled plasma mass spectroscopy. Electron microscopy confirmed colocalization of ESMA with elastic fibers. Changes in elastin content could be readily delineated and quantified at different stages of AAAs by elastin-specific molecular magnetic resonance imaging. ESMA-MRI offers potential for the noninvasive detection of the aortic rupture site prior to dilation of the aorta and the subsequent in vivo monitoring of compensatory repair processes during the progression of AAAs. © 2014 American Heart Association, Inc.

A NASTRAN Vibration Model of the AH-1G Helicopter Airframe. Volume 1

DTIC Science & Technology

1974-06-01

Bulkhead .012 ZZ 1863343 Bulkhead .012 AAA 1863345 Bulkhead .012 j EBB 1863546 Bulkhead .012 j ccc 1863746 Bulkhead .012 \\ ODD 1863748...123 12) 123 RULE AAA AAA AAA AAA BBB EBB AAA AAA AAA AAA BBB BBB OMIT D.O.F. 456 456 123 123 123 123 123 123 123 123 RULE...load in the member Increases. The program determines the section properties, unsytnmetrical bending stresses, element loads and shear flows for a

Recombinant adeno-associated virus vector carrying the thrombomodulin lectin-like domain for the treatment of abdominal aortic aneurysm.

PubMed

Lai, Chao-Han; Wang, Kuan-Chieh; Kuo, Cheng-Hsiang; Lee, Fang-Tzu; Cheng, Tsung-Lin; Chang, Bi-Ing; Yang, Yu-Jen; Shi, Guey-Yueh; Wu, Hua-Lin

2017-07-01

Thrombomodulin (TM), through its lectin-like domain (TMD1), sequesters proinflammatory high-mobility group box 1 (HMGB1) to prevent it from engaging the receptor for advanced glycation end product (RAGE) that sustains inflammation and tissue damage. Our previous study demonstrated that short-term treatment with recombinant TM containing all the extracellular domains (i.e., rTMD123) inhibits HMGB1-RAGE signaling and confers protection against CaCl 2 -induced AAA formation. In this study, we attempted to further optimize TM domains, as a potential therapeutic agent for AAA, using the recombinant adeno-associated virus (AAV) vector. The therapeutic effects of recombinant TMD1 (rTMD1) and recombinant AAV vectors carrying the lectin-like domain of TM (rAAV-TMD1) were evaluated in the CaCl 2 -induced AAA model and angiotensin II-infused AAA model, respectively. In the CaCl 2 -induced model, treatment with rTMD1 suppressed the tissue levels of HMGB1 and RAGE, macrophage accumulation, elastin destruction and AAA formation, and the effects were comparable to a mole-equivalent dosage of rTMD123. In the angiotensin II-infused model, a single intravenous injection of rAAV-TMD1 (10 11 genome copies), which resulted in a persistently high serum level of TMD1 for at least 12 weeks, effectively attenuated AAA formation with suppression of HMGB1 and RAGE levels and inhibition of proinflammatory cytokine production, macrophage accumulation, matrix metalloproteinase activities and oxidative stress in the aortic wall. These findings corroborate the therapeutic potential of the TM lectin-like domain in AAA. The attenuation of angiotensin II-infused AAA by one-time delivery of rAAV-TMD1 provides a proof-of-concept validation of its application as potential gene therapy for aneurysm development. Copyright © 2017 Elsevier B.V. All rights reserved.

Hypoperfusion of the Adventitial Vasa Vasorum Develops an Abdominal Aortic Aneurysm

PubMed Central

Sasaki, Takeshi; Sano, Masaki; Yamamoto, Naoto; Saito, Takaaki; Inuzuka, Kazunori; Hayasaka, Takahiro; Goto-Inoue, Naoko; Sugiura, Yuki; Sato, Kohji; Kugo, Hirona; Moriyama, Tatsuya; Konno, Hiroyuki; Setou, Mitsutoshi; Unno, Naoki

2015-01-01

The aortic wall is perfused by the adventitial vasa vasorum (VV). Tissue hypoxia has previously been observed as a manifestation of enlarged abdominal aortic aneurysms (AAAs). We sought to determine whether hypoperfusion of the adventitial VV could develop AAAs. We created a novel animal model of adventitial VV hypoperfusion with a combination of a polyurethane catheter insertion and a suture ligation of the infrarenal abdominal aorta in rats. VV hypoperfusion caused tissue hypoxia and developed infrarenal AAA, which had similar morphological and pathological characteristics to human AAA. In human AAA tissue, the adventitial VV were stenotic in both small AAAs (30–49 mm in diameter) and in large AAAs (> 50 mm in diameter), with the sac tissue in these AAAs being ischemic and hypoxic. These results indicate that hypoperfusion of adventitial VV has critical effects on the development of infrarenal AAA. PMID:26308526

On the potential increase of the oxidative stress status in patients with abdominal aortic aneurysm.

PubMed

Pincemail, J; Defraigne, J O; Cheramy-Bien, J P; Dardenne, N; Donneau, A F; Albert, A; Labropoulos, N; Sakalihasan, N

2012-01-01

Abdominal aortic aneurysm (AAA) is a major cause of preventable deaths in older patients. Oxidative stress has been suggested to play a key role in the pathogenesis of AAA. However, only few studies have been conducted to evaluate the blood oxidative stress status of AAA patients. Twenty seven AAA patients (mean age of 70 years) divided into two groups according to AAA size (≤ 50 or > 50 mm) were compared with an age-matched group of 18 healthy subjects. Antioxidants (vitamins C and E, β-carotene, glutathione, thiols, and ubiquinone), trace elements (selenium, copper, zinc, and copper/zinc ratio) and markers of oxidative damage to lipids (lipid peroxides, antibodies against oxidized patients, and isoprostanes) were measured in each subject. The comparison of the three groups by ordinal logistic regression showed a significant decrease of the plasma levels of vitamin C (P = 0.011), α-tocopherol (P = 0.016) but not when corrected for cholesterol values, β-carotene (P = 0.0096), ubiquinone (P = 0.014), zinc (P = 0.0035), and of selenium (P = 0.0038), as AAA size increased. By contrast, specific markers of lipid peroxidation such as the Cu/Zn ratio (P = 0.046) and to a lesser extent isoprostanes (P = 0.052) increased. The present study emphasizes the potential role of the oxidative stress in AAA disease and suggests that an antioxidant therapy could be of interest to delay AAA progression.

Staff members' perceptions of an animal-assisted activity.

PubMed

Bibbo, Jessica

2013-07-01

To examine the perceptions of staff members toward the implementation of an animal-assisted activity (AAA) in an outpatient regional cancer center. Quasi-experimental, post-test design. An adult outpatient regional cancer center in northern California. 34 facility staff members. Self-report questionnaire following four weeks of AAA visitation. Visits took place three times a week for a total of 12 visits. Perceptions of the AAA. Previous perceptions toward AAA influenced the perceptions of the visitation's efficacy. Direct and indirect interaction with the visiting AAA teams was positively associated with perceptions of the AAA. A disagreement occurred that the AAA had caused extra stress or work for staff. Enjoyment of interacting with the dog handler was not significantly different from interacting with the dog; however, it was more positively correlated to acceptance of the AAA. The study provided evidence that the AAA was generally accepted by staff members. Individual staff members' perceptions of dogs and AAAs can influence their receptivity to AAA interventions. Interaction with AAA teams should be voluntary and available for patients and staff members. AAA may be introduced into facilities without creating the perception of extra stress or work for staff members. Providing staff the opportunity to interact with visiting AAA teams may be beneficial for the success of such programs. The human handler in AAA teams may play a vital role in the staff acceptance of such programs.

Oxidative Stress in Aortas of Patients with Advanced Occlusive and Aneurysmal Diseases.

PubMed

Lucas, Márcio L; Carraro, Cristina C; Belló-Klein, Adriane; Kalil, Antônio N; Aerts, Newton R; Carvalho, Fabiano B; Fernandes, Marilda C; Zettler, Claudio G

2018-06-06

Aortoiliac occlusive disease (AOD) and abdominal aortic aneurysm (AAA) are very important cardiovascular diseases that present different aspects of pathophysiology; however, oxidative stress and inflammatory response seem be relevant in both of them. Our objective was to evaluate oxidative damage and degree of inflammatory infiltrate in aortas of patients surgically treated for AOD and AAA. Levels of reactive oxygen species (ROS), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, and myeloperoxidase (MPO) expression as well as nitrite levels and superoxide dismutase (SOD) and catalase (CAT) activities were evaluated in aortas of patients with AOD (n = 16) or AAA (n = 14), while the control group was formed by cadaveric organ donors (n = 10). We also analyzed the degree of inflammatory infiltrate in these aortas. There was an increase in ROS levels and NADPH oxidase activity in patients with AOD and AAA when compared with the control group, and the AOD group demonstrated higher ROS production and NADPH oxidase activity and also nitrite levels when compared with the AAA group (P < 0.001). On the other hand, an increase of SOD activity in the AOD group and CAT activity in the AAA group was observed. Inflammatory infiltrate and MPO expression were higher in the AOD group when compared with the control group (P < 0.05). Oxidative stress is relevant in both AOD and AAA, though AOD presented higher ROS levels and NADPH activity. Increased activities of antioxidant enzymes may be a compensatory phenomenon which occurs in aortas of patients with AOD and AAA. Perhaps, a relationship between oxidative stress and degree of inflammatory infiltrate may exist in the pathophysiology of AOD and AAA. Copyright © 2018 Elsevier Inc. All rights reserved.

Quantitative expression and localization of cysteine and aspartic proteases in human abdominal aortic aneurysms

PubMed Central

Lohoefer, Fabian; Reeps, Christian; Lipp, Christina; Rudelius, Martina; Haertl, Felix; Matevossian, Edouard; Zernecke, Alma; Eckstein, Hans-Henning; Pelisek, Jaroslav

2014-01-01

Cysteine and aspartic proteases possess high elastolytic activity and might contribute to the degradation of the abdominal aortic aneurysm (AAA) wall. The aim of this study was to analyze, in detail, the proteases (cathepsins B, D, K, L and S, and inhibitor cystatin C) found in human AAA and healthy aortic tissue samples. The vessel walls from AAA patients (n=36) and nonaneurysmal aortae (n=10) were retrieved using conventional surgical repair and autopsy methods. Serum samples from the same AAA patients and 10 healthy volunteers were also collected. Quantitative expression analyses were performed at the mRNA level using real-time reverse transcriptase-PCR (RT–PCR). Furthermore, analyses at the protein level included western blot and immunoprecipitation analyses. Cellular sources of cysteine/aspartic proteases and cystatin C were identified by immunohistochemistry (IHC). All cysteine/aspartic proteases and cystatin C were detected in the AAA and control samples. Using quantitative RT–PCR, a significant increase in expression was observed for cathepsins B (P=0.021) and L (P=0.018), compared with the controls. Cathepsin B and cystatin C were also detected in the serum of AAA patients. Using IHC, smooth muscle cells (SMCs) and macrophages were positive for all of the tested cathepsins, as well as cystatin C; in addition, the lymphocytes were mainly positive for cathepsin B, followed by cathepsins D and S. All cysteine/aspartic proteases analyzed in our study were detected in the AAA and healthy aorta. The highest expression was found in macrophages and SMCs. Consequently, cysteine/aspartic proteases might play a substantial role in AAA. PMID:24833013

Tissue factor levels and the fibrinolytic system in thin and thick intraluminal thrombus and underlying walls of abdominal aortic aneurysms.

PubMed

Siennicka, Aldona; Zuchowski, Marta; Kaczmarczyk, Mariusz; Cnotliwy, Miłosław; Clark, Jeremy Simon; Jastrzębska, Maria

2018-03-20

The hemostatic system cooperates with proteolytic degradation in processes allowing abdominal aortic aneurysm (AAA) formation. In previous studies, it has been suggested that aneurysm rupture depends on intraluminal thrombus (ILT) thickness, which varies across each individual aneurysm. We hypothesized that hemostatic components differentially accumulate in AAA tissue in relation to ILT thickness. Thick (A1) and thin (B1) segments of ILTs and aneurysm wall sections A (adjacent to A1) and B (adjacent to B1) from one aneurysm sac were taken from 35 patients undergoing elective repair. Factor levels were measured using enzyme-linked immunosorbent assay of protein extract. Tissue factor (TF) activities were significantly higher in thinner segments of AAA (B1 vs A1, P = .003; B vs A, P < .001; B vs A1, P < .001; B vs B1, P = .001). Significantly higher tissue plasminogen activator was found in thick thrombus-covered wall segments (A) than in B, A1, and B1 (P = .015, P < .001, and P < .001, respectively). Plasminogen concentrations were highest in ILT. Concentrations of α 2 -antiplasmin in thin ILT adjacent walls (B) were higher compared with wall (A) adjacent to thick ILT (P = .021) and thick ILT (A1; P < .001). Significant correlations between levels of different factors were mostly found in thick ILT (A1). However, no correlations were found at B sites, except for a correlation between plasmin and TF activities (r = 0.55; P = .004). These results suggest that higher TF activities are present in thinner AAA regions. These parameters and local fibrinolysis may be part of the processes leading to destruction of the aneurysm wall. Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Does lower limb exercise worsen renal artery hemodynamics in patients with abdominal aortic aneurysm?

PubMed

Sun, Anqiang; Tian, Xiaopeng; Zhang, Nan; Xu, Zaipin; Deng, Xiaoyan; Liu, Ming; Liu, Xiao

2015-01-01

Renal artery stenosis (RAS) and renal complications emerge in some patients after endovascular aneurysm repair (EVAR) to treat abdominal aorta aneurysm (AAA). The mechanisms for the causes of these problems are not clear. We hypothesized that for EVAR patients, lower limb exercise could negatively influence the physiology of the renal artery and the renal function, by decreasing the blood flow velocity and changing the hemodynamics in the renal arteries. To evaluate this hypothesis, pre- and post-operative models of the abdominal aorta were reconstructed based on CT images. The hemodynamic environment was numerically simulated under rest and lower limb exercise conditions. The results revealed that in the renal arteries, lower limb exercise decreased the wall shear stress (WSS), increased the oscillatory shear index (OSI) and increased the relative residence time (RRT). EVAR further enhanced these effects. Because these parameters are related to artery stenosis and atherosclerosis, this preliminary study concluded that lower limb exercise may increase the potential risk of inducing renal artery stenosis and renal complications for AAA patients. This finding could help elucidate the mechanism of renal artery stenosis and renal complications after EVAR and warn us to reconsider the management and nursing care of AAA patients.

Abdominal aortic aneurysms: an autoimmune disease?

PubMed

Jagadesham, Vamshi P; Scott, D Julian A; Carding, Simon R

2008-12-01

Abdominal aortic aneurysms (AAAs) are a multifactorial degenerative vascular disorder. One of the defining features of the pathophysiology of aneurysmal disease is inflammation. Recent developments in vascular and molecular cell biology have increased our knowledge on the role of the adaptive and innate immune systems in the initiation and propagation of the inflammatory response in aortic tissue. AAAs share many features of autoimmune disease, including genetic predisposition, organ specificity and chronic inflammation. Here, this evidence is used to propose that the chronic inflammation observed in AAAs is a consequence of a dysregulated autoimmune response against autologous components of the aortic wall that persists inappropriately. Identification of the molecular and cellular targets involved in AAA formation will allow the development of therapeutic agents for the treatment of AAA.

Effect of a High-sucrose Diet on Abdominal Aortic Aneurysm Development in a Hypoperfusion-induced Animal Model.

PubMed

Miyamoto, Chie; Kugo, Hirona; Hashimoto, Keisuke; Sawaragi, Ayaka; Zaima, Nobuhiro; Moriyama, Tatsuya

2018-05-01

Abdominal aortic aneurysm (AAA) is a vascular disease that results in rupture of the abdominal aorta. The risk factors for the development of AAA include smoking, male sex, hypertension, and age. AAA has a high mortality rate, but therapy for AAA is restricted to surgery in cases of large aneurysms. Clarifying the effect of dietary food on the development of AAA would be helpful for patients with AAAs. However, the relationship between dietary habits and the development of AAA is largely unknown. In our previous study, we demonstrated that adipocytes in vascular wall can induce the rupture of AAA. Therefore, we focused on the diet-induced abnormal triglyceride metabolism, which has the potential to drive AAA development. In this study, we have evaluated the effects of a high-sucrose diet on the development of AAA in a vascular hypoperfusion-induced animal model. A high sucrose diet induced high serum TG level and fatty liver. However, the AAA rupture risk and the AAA diameter were not significantly different between the control and high-sucrose groups. The intergroup differences in the elastin degradation score and collagen-positive area were insignificant. Moreover, matrix metalloproteinases, macrophages, and monocyte chemoattractant protein-1-positive areas did not differ significantly between groups. These results suggest that a high-sucrose diet does not affect the appearance of vascular adipocyte and AAA development under the vascular hypoperfusion condition.

Increased 18F-FDG Uptake Is Predictive of Rupture in a Novel Rat Abdominal Aortic Aneurysm Rupture Model

PubMed Central

English, Sean J.; Piert, Morand R.; Diaz, Jose A.; Gordon, David; Ghosh, Abhijit; D'Alecy, Louis G.; Whitesall, Steven E.; Sharma, Ashish K.; DeRoo, Elise P.; Watt, Tessa; Su, Gang; Henke, Peter K.; Eliason, Jonathan L.; Ailawadi, Gorav; Upchurch, Gilbert R.

2015-01-01

Objective To determine whether 18F-fluorodeoxyglucose (18F-FDG) micro–positron emission tomography (micro-PET) can predict abdominal aortic aneurysm (AAA) rupture. Background An infrarenal AAA model is needed to study inflammatory mechanisms that drive rupture. 18F-FDG PET can detect vascular inflammation in animal models and patients. Methods After exposing Sprague-Dawley rats to intra-aortic porcine pancreatic elastase (PPE) (12 U/mL), AAA rupture was induced by daily, subcutaneous, β-aminopropionitrile (BAPN, 300 mg/kg, N = 24) administration. Negative control AAA animals (N = 15) underwent daily saline subcutaneous injection after PPE exposure. BAPN-exposed animals that did not rupture served as positive controls [nonruptured AAA (NRAAA) 14d, N = 9]. Rupture was witnessed using radiotelemetry. Maximum standard uptakes for 18F-FDG micro-PET studies were determined. Aortic wall PAI-1, uPA, and tPA concentrations were determined by western blot analyses. Interleukin (IL)-1β, IL-6, IL-10, and MIP-2 were determined by Bio-Plex bead array. Neutrophil and macrophage populations per high-power field were quantified. Matrix metalloproteinase (MMP) activities were determined by zymography. Results When comparing ruptured AAA (RAAA) to NRAAA 14d animals, increased focal 18F-FDG uptakes were detected at subsequent sites of rupture (P = 0.03). PAI-1 expression was significantly less in RAAA tissue (P = 0.01), with comparable uPA and decreased tPA levels (P = 0.02). IL-1β (P = 0.04), IL-6 (P = 0.001), IL-10 (P = 0.04), and MIP-2 (P = 0.02)expression, neutrophil (P = 0.02) and macrophage presence (P = 0.002), and MMP9 (P < 0.0001) activity were increased in RAAA tissue. Conclusions With this AAA rupture model, increased prerupture 18F-FDG uptake on micro-PET imaging was associated with increased inflammation in the ruptured AAA wall. 18F-FDG PET imaging may be used to monitor inflammatory changes before AAA rupture. PMID:24651130

Quantitative HDL Proteomics Identifies Peroxiredoxin-6 as a Biomarker of Human Abdominal Aortic Aneurysm

PubMed Central

Burillo, Elena; Jorge, Inmaculada; Martínez-López, Diego; Camafeita, Emilio; Blanco-Colio, Luis Miguel; Trevisan-Herraz, Marco; Ezkurdia, Iakes; Egido, Jesús; Michel, Jean-Baptiste; Meilhac, Olivier; Vázquez, Jesús; Martin-Ventura, Jose Luis

2016-01-01

High-density lipoproteins (HDLs) are complex protein and lipid assemblies whose composition is known to change in diverse pathological situations. Analysis of the HDL proteome can thus provide insight into the main mechanisms underlying abdominal aortic aneurysm (AAA) and potentially detect novel systemic biomarkers. We performed a multiplexed quantitative proteomics analysis of HDLs isolated from plasma of AAA patients (N = 14) and control study participants (N = 7). Validation was performed by western-blot (HDL), immunohistochemistry (tissue), and ELISA (plasma). HDL from AAA patients showed elevated expression of peroxiredoxin-6 (PRDX6), HLA class I histocompatibility antigen (HLA-I), retinol-binding protein 4, and paraoxonase/arylesterase 1 (PON1), whereas α-2 macroglobulin and C4b-binding protein were decreased. The main pathways associated with HDL alterations in AAA were oxidative stress and immune-inflammatory responses. In AAA tissue, PRDX6 colocalized with neutrophils, vascular smooth muscle cells, and lipid oxidation. Moreover, plasma PRDX6 was higher in AAA (N = 47) than in controls (N = 27), reflecting increased systemic oxidative stress. Finally, a positive correlation was recorded between PRDX6 and AAA diameter. The analysis of the HDL proteome demonstrates that redox imbalance is a major mechanism in AAA, identifying the antioxidant PRDX6 as a novel systemic biomarker of AAA. PMID:27934969

Endothelin-1 overexpression exacerbates atherosclerosis and induces aortic aneurysms in apolipoprotein E knockout mice.

PubMed

Li, Melissa W; Mian, Muhammad Oneeb Rehman; Barhoumi, Tlili; Rehman, Asia; Mann, Koren; Paradis, Pierre; Schiffrin, Ernesto L

2013-10-01

Endothelin (ET)-1 plays a role in vascular reactive oxygen species production and inflammation. ET-1 has been implicated in human atherosclerosis and abdominal aortic aneurysm (AAA) development. ET-1 overexpression exacerbates high-fat diet-induced atherosclerosis in apolipoprotein E(-/-) (Apoe(-/-)) mice. ET-1-induced reactive oxygen species and inflammation may contribute to atherosclerosis progression and AAA development. Eight-week-old male wild-type mice, transgenic mice overexpressing ET-1 selectively in endothelium (eET-1), Apoe(-/-) mice, and eET-1/Apoe(-/-) mice were fed high-fat diet for 8 weeks. eET-1/Apoe(-/-) had a 45% reduction in plasma high-density lipoprotein (P<0.05) and presented ≥ 2-fold more aortic atherosclerotic lesions compared with Apoe(-/-) (P<0.01). AAAs were detected only in eET-1/Apoe(-/-) (8/21; P<0.05). Reactive oxygen species production was increased ≥ 2-fold in perivascular fat, media, or atherosclerotic lesions in the ascending aorta and AAAs of eET-1/Apoe(-/-) compared with Apoe(-/-) (P<0.05). Monocyte/macrophage infiltration was enhanced ≥ 2.5-fold in perivascular fat of ascending aorta and AAAs in eET-1/Apoe(-/-) compared with Apoe(-/-) (P<0.05). CD4(+) T cells were detected almost exclusively in perivascular fat (3/6) and atherosclerotic lesions (5/6) in ascending aorta of eET-1/Apoe(-/-) (P<0.05). The percentage of spleen proinflammatory Ly-6C(hi) monocytes was enhanced 26% by ET-1 overexpression in Apoe(-/-) (P<0.05), and matrix metalloproteinase-2 was increased 2-fold in plaques of eET-1/Apoe(-/-) (P<0.05) compared with Apoe(-/-). ET-1 plays a role in progression of atherosclerosis and AAA formation by decreasing high-density lipoprotein, and increasing oxidative stress, inflammatory cell infiltration, and matrix metalloproteinase-2 in perivascular fat, vascular wall, and atherosclerotic lesions.

A Relation Between Near-Wall Particle-Hemodynamics and Onset of Thrombus Formation in Abdominal Aortic Aneurysms

PubMed Central

Basciano, C.; Kleinstreuer, C.; Hyun, S.; Finol, E. A.

2014-01-01

A novel computational particle-hemodynamics analysis of key criteria for the onset of an intraluminal thrombus (ILT) in a patient-specific abdominal aortic aneurysm (AAA) is presented. The focus is on enhanced platelet and white blood cell residence times as well as their elevated surface-shear loads in near-wall regions of the AAA sac. The generalized results support the hypothesis that a patient's AAA geometry and associated particle-hemodynamics have the potential to entrap activated blood particles, which will play a role in the onset of ILT. Although the ILT history of only a single patient was considered, the modeling and simulation methodology provided allow for the development of an efficient computational tool to predict the onset of ILT formation in complex patient-specific cases. PMID:21373952

Abdominal aorta aneurysm (AAA): Is there a role for prevention and therapy using antioxidants?

PubMed

Pincemail, Joël; Defraigne, Jean-Olivier; Courtois, Audrey; Albert, Adelin; Cheramy-Bien, Jean-Paul; Sakalihasan, Natzi

2017-09-18

Abdominal aortic aneurysm (AAA) is a degenerative disease that cause mortality in people aged > 65 years. Increased reactive oxygen species (ROS) and oxidative stress seems to play a pivotal role in AAA pathogenesis. Several sources of ROS have been identified in aortic tissues using experimental models: inflammation, increased activity of NAD(P)H or NOX, over-expression of inducible nitric oxide synthase (iNOS), uncoupled endothelial nitric oxide synthase (eNOS), platelets activation and iron release from hemoglobin. Reducing oxidative stress by antioxidants has been shown to be a potential strategy for limiting AAA development. Human studies confirmed that oxidative stress and endothelial dysfunction are well associated with AAA development. Unfortunately, there is currently no evidence showing that strategies using low molecular weight antioxidants (vitamins C and E, β-carotene) as target for ROS is effective to reduce human AAA progression. However, recent epidemiological data have highlighted the positive role of a diet enriched in fruits which contain high amounts of antioxidant polyphenols. By their ability to restore endothelial function but also their capacity to stimulate enzymatic antioxidants trough activation of the Keap1/Nrf2/ARE pathway, polyphenols can represent a promising treatment target for reducing human AAA progression. Clinical studies are therefore urgently necessary to confirm such a suggestion. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Evaluation of the thrombus of abdominal aortic aneurysms using contrast enhanced ultrasound - preliminary results

NASA Astrophysics Data System (ADS)

Łukasiewicz, Adam; Garkowski, Adam; Rutka, Katarzyna; Janica, Jacek; Łebkowska, Urszula

2016-09-01

It is hypothesized that the degree of vascularization of the thrombus may have a significant impact on the rupture of aortic aneurysms. The presence of neovascularization of the vessel wall and mural thrombus has been confirmed only in histopathological studies. However, no non-invasive imaging technique of qualitative assessment of thrombus and neovascularization has been implemented so far. Contrast-enhanced ultrasound (CEUS) has been proposed as a feasible and minimally invasive technique for in vivo visualization of neovascularization in the evaluation of tumors and atherosclerotic plaques. The aim of this study was the evaluation of mural thrombus and AAAs wall with CEUS. CEUS was performed in a group of seventeen patients with AAAs. The mural thrombus enhancement was recognized in 12 cases, yet no significant correlation between the degree of contrast enhancement and AAAs diameter, thrombus width, and thrombus echogenicity was found. We observed a rise in AAAs thrombus heterogeneity with the increase in the aneurysm diameter (r = 0.62, p = 0.017). In conclusion CEUS can visualize small channels within AAAs thrombus, which could be a result of an ongoing angiogenesis. There is a need for further research to find out whether the degree of vascularization of the thrombus may have a significant impact on the rupture of aneurysms.

Reproducibility of ECG-gated ultrasound diameter assessment of small abdominal aortic aneurysms.

PubMed

Bredahl, K; Eldrup, N; Meyer, C; Eiberg, J E; Sillesen, H

2013-03-01

No standardised ultrasound procedure to obtain reliable growth estimates for abdominal aortic aneurysms (AAA) is currently available. We investigated the feasibility and reproducibility of a novel approach controlling for a combination of vessel wall delineation and cardiac cycle variation. Prospective comparative study. Consecutive patients (N = 27) with an AAA, attending their 6-month control as part of a medical treatment trial, were scanned twice by two ultrasound operators. Then, all ultrasound recordings were transferred to a core facility and analysed by a third person. The AAA diameter was determined in four different ways: from the leading edge of adventitia on the anterior wall to either the leading edge of the adventitia (method A) or leading edge of the intima (method B) on the posterior wall, with both measurements performed in systole and diastole. Inter-operator reproducibility was ± 3 mm for all methods applied. There was no difference in outcome between methods A and B; likewise, end-diastolic measurement did not improve reproducibility in preference to peak-systolic measurement. The use of a standardised ultrasound protocol including ECG-gating and subsequent off-line reading with minute calliper placement reduces variability. This may be of use in developing protocols to better detect even small AAA growth rates during clinical trials. Copyright © 2012 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

18F-FDG uptake assessed by PET/CT in abdominal aortic aneurysms is associated with cellular and molecular alterations prefacing wall deterioration and rupture.

PubMed

Courtois, Audrey; Nusgens, Betty V; Hustinx, Roland; Namur, Gauthier; Gomez, Pierre; Somja, Joan; Defraigne, Jean-Olivier; Delvenne, Philippe; Michel, Jean-Baptiste; Colige, Alain C; Sakalihasan, Natzi

2013-10-01

Rupture of abdominal aortic aneurysms (AAAs) leads to a significant morbidity and mortality in aging populations, and its prediction would be most beneficial to public health. Spots positive for uptake of (18)F-FDG detected by PET are found in 12% of AAA patients (PET+), who are most often symptomatic and at high rupture risk. Comparing the (18)F-FDG-positive site with a negative site from the same aneurysm and with samples collected from AAA patients with no (18)F-FDG uptake should allow the discrimination of biologic alterations that would help in identifying markers predictive of rupture. Biopsies of the AAA wall were obtained from patients with no (18)F-FDG uptake (PET0, n = 10) and from PET+ patients (n = 8), both at the site positive for uptake and at a distant negative site of the aneurysmal wall. Samples were analyzed by immunohistochemistry, quantitative real-time polymerase chain reaction, and zymography. The sites of the aneurysmal wall with a positive (18)F-FDG uptake were characterized by a strikingly increased number of adventitial inflammatory cells, highly proliferative, and by a drastic reduction of smooth muscle cells (SMCs) in the media as compared with their negative counterpart and with the PET0 wall. The expression of a series of genes involved in the maintenance and remodeling of the wall was significantly modified in the negative sites of PET+, compared with the PET0 wall, suggesting a systemic alteration of the aneurysmal wall. Furthermore, a striking increase of several matrix metalloproteinases (MMPs), notably the MMP1 and MMP13 collagenases, was observed in the positive sites, mainly in the adventitia. Moreover, PET+ patients were characterized by a higher circulating C-reactive protein. Positive (18)F-FDG uptake in the aneurysmal wall is associated with an active inflammatory process characterized by a dense infiltrate of proliferating leukocytes in the adventitia and an increased circulating C-reactive protein. Moreover, a loss of SMC in the media and alterations of the expression of genes involved in the remodeling of adventitia and collagen degradation potentially participate in the weakening of the aneurysmal wall preceding rupture.

Phenylalanine and tyrosine levels are rate-limiting factors in production of health promoting metabolites in Vitis vinifera cv. Gamay Red cell suspension

PubMed Central

Manela, Neta; Oliva, Moran; Ovadia, Rinat; Sikron-Persi, Noga; Ayenew, Biruk; Fait, Aaron; Galili, Gad; Perl, Avichai; Weiss, David; Oren-Shamir, Michal

2015-01-01

Environmental stresses such as high light intensity and temperature cause induction of the shikimate pathway, aromatic amino acids (AAA) pathways, and of pathways downstream from AAAs. The induction leads to production of specialized metabolites that protect the cells from oxidative damage. The regulation of the diverse AAA derived pathways is still not well understood. To gain insight on that regulation, we increased AAA production in red grape Vitis vinifera cv. Gamay Red cell suspension, without inducing external stress on the cells, and characterized the metabolic effect of this induction. Increased AAA production was achieved by expressing a feedback-insensitive bacterial form of 3-deoxy- D-arabino-heptulosonate 7-phosphate synthase enzyme (AroG*) of the shikimate pathway under a constitutive promoter. The presence of AroG* protein led to elevated levels of primary metabolites in the shikimate and AAA pathways including phenylalanine and tyrosine, and to a dramatic increase in phenylpropanoids. The AroG* transformed lines accumulated up to 20 and 150 fold higher levels of resveratrol and dihydroquercetin, respectively. Quercetin, formed from dihydroquercetin, and resveratrol, are health promoting metabolites that are induced due to environmental stresses. Testing the expression level of key genes along the stilbenoids, benzenoids, and phenylpropanoid pathways showed that transcription was not affected by AroG*. This suggests that concentrations of AAAs, and of phenylalanine in particular, are rate-limiting in production of these metabolites. In contrast, increased phenylalanine production did not lead to elevated concentrations of anthocyanins, even though they are also phenylpropanoid metabolites. This suggests a control mechanism of this pathway that is independent of AAA concentration. Interestingly, total anthocyanin concentrations were slightly lower in AroG* cells, and the relative frequencies of the different anthocyanins changed as well. PMID:26236327

Phenylalanine and tyrosine levels are rate-limiting factors in production of health promoting metabolites in Vitis vinifera cv. Gamay Red cell suspension.

PubMed

Manela, Neta; Oliva, Moran; Ovadia, Rinat; Sikron-Persi, Noga; Ayenew, Biruk; Fait, Aaron; Galili, Gad; Perl, Avichai; Weiss, David; Oren-Shamir, Michal

2015-01-01

Environmental stresses such as high light intensity and temperature cause induction of the shikimate pathway, aromatic amino acids (AAA) pathways, and of pathways downstream from AAAs. The induction leads to production of specialized metabolites that protect the cells from oxidative damage. The regulation of the diverse AAA derived pathways is still not well understood. To gain insight on that regulation, we increased AAA production in red grape Vitis vinifera cv. Gamay Red cell suspension, without inducing external stress on the cells, and characterized the metabolic effect of this induction. Increased AAA production was achieved by expressing a feedback-insensitive bacterial form of 3-deoxy- D-arabino-heptulosonate 7-phosphate synthase enzyme (AroG (*)) of the shikimate pathway under a constitutive promoter. The presence of AroG(*) protein led to elevated levels of primary metabolites in the shikimate and AAA pathways including phenylalanine and tyrosine, and to a dramatic increase in phenylpropanoids. The AroG (*) transformed lines accumulated up to 20 and 150 fold higher levels of resveratrol and dihydroquercetin, respectively. Quercetin, formed from dihydroquercetin, and resveratrol, are health promoting metabolites that are induced due to environmental stresses. Testing the expression level of key genes along the stilbenoids, benzenoids, and phenylpropanoid pathways showed that transcription was not affected by AroG (*). This suggests that concentrations of AAAs, and of phenylalanine in particular, are rate-limiting in production of these metabolites. In contrast, increased phenylalanine production did not lead to elevated concentrations of anthocyanins, even though they are also phenylpropanoid metabolites. This suggests a control mechanism of this pathway that is independent of AAA concentration. Interestingly, total anthocyanin concentrations were slightly lower in AroG(*) cells, and the relative frequencies of the different anthocyanins changed as well.

Heterogeneous histomorphology, yet homogeneous vascular smooth muscle cell dedifferentiation, characterize human aneurysm disease.

PubMed

Busch, Albert; Hartmann, Elena; Grimm, Caroline; Ergün, Süleyman; Kickuth, Ralph; Otto, Christoph; Kellersmann, Richard; Lorenz, Udo

2017-11-01

Abdominal aortic aneurysm (AAA) is a frequent, potentially life-threatening, disease that can only be treated by surgical means such as open surgery or endovascular repair. No alternative treatment is currently available, and despite expanding knowledge about the pathomechanism, clinical trials on medical aneurysm abrogation have led to inconclusive results. The heterogeneity of human AAA based on histologic examination is thereby generally neglected. In this study we aimed to further elucidate the role of these differences in aneurysm disease. Tissue samples from AAA and popliteal artery aneurysm patients were examined by histomorphologic analysis, immunohistochemistry, Western blot, and polymerase chain reaction. The results were correlated with clinical data such as aneurysm diameter and laboratory results. The morphology of human AAA vessel wall probes varies tremendously based on the grade of inflammation. This correlates with increasing intima/media thickness and upregulation of the vascular endothelial growth factor cascade but not with any clinical parameter or the aneurysm diameter. The phenotypic switch of vascular smooth muscle cells occurred regardless of the inflammatory state and expressional changes of the transcription factors Kruppel-like factor-4 and transforming growth factor-β lead to differential protein localization in aneurysmal compared with control arteries. These changes were in similar manner also observed in samples from popliteal artery aneurysms, which, however, showed a more homogenous phenotype. Heterogeneity of AAA vessel walls based on inflammatory morphology does not correlate with AAA diameter yet harbors specific implications for basic research and possible aneurysm detection. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

The effects of nicotine administration on the pathophysiology of rat aortic wall.

PubMed

Kugo, H; Zaima, N; Tanaka, H; Urano, T; Unno, N; Moriyama, T

2017-01-01

Abdominal aortic aneurysm (AAA) is the progressive dilation of the abdominal aorta. Nicotine is reported to be associated with the development and rupture of AAA, but the pathological effects of nicotine on normal rat aorta have not been determined. We investigated pathological changes in the aortic wall of rats caused by the administration of nicotine. Nicotine administration weakened the vascular wall, increased gelatinolytic activity and promoted the destruction of elastin and collagen in the rat abdominal aorta. There were no differences in the areas positive for matrix metalloproteinase (MMP)-2 and MMP-9 between the control and nicotine treated groups. The areas positive for MMP-12 in the nicotine group were significantly greater than for the control group. Gelatinolytic activity in the aortic wall was increased significantly in the nicotine group. Our findings suggest that MMP-12 is sensitive to nicotine exposure in rats.

[A study on residual strain of abdominal aortic aneurysm after intraperitoneal administration of saturated hydrogen saline in rats].

PubMed

Song, Yuxiang; Chen, Feng; Xiong, Jiang; Guo, Wei; Pan, Xiujie; Jia, Senhao; Liu, Jie

2013-07-01

By observation of the diameter, progression rate, wall thickness, and the opening angle of the abnormal aortic of abdominal aortic aneurysm (AAA) in rats, to observe the effect of saturated hydrogen saline on residual strain of AAA rats, and to investigate its inhibition effect on AAA formation. Twenty healthy male Sprague Dawley rats (weighing, 200-220 g) were randomly divided into 2 groups, which was made the AAA model by infiltration of the abdominal arota with 0.5 mol/L calcium chloride. Saturated hydrogen saline (5 mL/kg) or saline (5 mL/kg) was injected intraperitoneally in the experimental group or control group respectively, every day for 28 days. At 28 days, the diameter, progression rate, wall thickness, and opening angle of the abnormal aorta were mearsured. The aortic tissue was harvested for histological examination (HE staining and aldehyde-fuchsin staining). At 28 days after operation, the diameter of abnormal aorta in 2 groups were significantly higher than preoperative ones (P < 0.05), the progression rate in experimental group (65% +/- 15%) was significantly lower than that in control group (128% +/- 54%) (t=3.611, P=0.005). The opening angle and the wall thickness in experimental group were (88.78 +/- 29.20) degrees and (0.14 +/- 0.03) mm respectively, had significant differences when compared with the values in control group [(44.23 +/- 28.52) degrees and (0.36 +/- 0.05) mm respectively] (P < 0.01). The integrity and continuity of the aortic wall in experimental group were superior to that in the control group. Compared with the control group, the injury of elastic fiber in aortic wall and the infiltration of inflammation were all reduced. Saturated hydrogen saline can maintain good mechanical properties and reduce dilatation of the aorta by increasing residual strain and reducing the remodeling of it.

Update on Abdominal Aortic Aneurysm Research: From Clinical to Genetic Studies

PubMed Central

Kuivaniemi, Helena; Ryer, Evan J.; Elmore, James R.; Hinterseher, Irene; Smelser, Diane T.; Tromp, Gerard

2014-01-01

An abdominal aortic aneurysm (AAA) is a dilatation of the abdominal aorta with a diameter of at least 3.0 cm. AAAs are often asymptomatic and are discovered as incidental findings in imaging studies or when the AAA ruptures leading to a medical emergency. AAAs are more common in males than females, in individuals of European ancestry, and in those over 65 years of age. Smoking is the most important environmental risk factor. In addition, a positive family history of AAA increases the person's risk for AAA. Interestingly, diabetes has been shown to be a protective factor for AAA in many large studies. Hallmarks of AAA pathogenesis include inflammation, vascular smooth muscle cell apoptosis, extracellular matrix degradation, and oxidative stress. Autoimmunity may also play a role in AAA development and progression. In this Outlook paper, we summarize our recent studies on AAA including clinical studies related to surgical repair of AAA and genetic risk factor and large-scale gene expression studies. We conclude with a discussion on our research projects using large data sets available through electronic medical records and biobanks. PMID:24834361

Advanced Oxidation Protein Products and Carbonylated Proteins as Biomarkers of Oxidative Stress in Selected Atherosclerosis-Mediated Diseases.

PubMed

Gryszczyńska, Bogna; Formanowicz, Dorota; Budzyń, Magdalena; Wanic-Kossowska, Maria; Pawliczak, Elżbieta; Formanowicz, Piotr; Majewski, Wacław; Strzyżewski, Krzysztof Wojciech; Kasprzak, Magdalena P; Iskra, Maria

2017-01-01

The main question of this study was to evaluate the intensity of oxidative protein modification shown as advanced oxidation protein products (AOPP) and carbonylated proteins, expressed as protein carbonyl content (C=O) in abdominal aortic aneurysms (AAA), aortoiliac occlusive disease (AIOD), and chronic kidney disease (CKD). The study was carried out in a group of 35 AAA patients and 13 AIOD patients. However, CKD patients were divided into two groups: predialysis (PRE) included 50 patients or hemodialysis (HD) consisted of 34 patients. AOPP and C=O were measured using colorimetric assay kit, while C-reactive protein concentration was measured by high-sensitivity assay (hsCRP). The concentration of AOPP in both AAA and AIOD groups was higher than in PRE and HD groups according to descending order: AAA~AIOD > HD > PRE. The content of C=O was higher in the PRE group in comparison to AIOD and AAA according to the descending order: PRE~HD > AAA~AIOD. AAA, AIOD, and CKD-related atherosclerosis (PRE and HD) contribute to the changes in the formation of AOPP and C=O. They may promote modification of proteins in a different way, probably due to the various factors that influence oxidative stress here.

Inhibition of endoplasmic reticulum stress by intermedin1-53 attenuates angiotensin II-induced abdominal aortic aneurysm in ApoE KO Mice.

PubMed

Ni, Xian-Qiang; Lu, Wei-Wei; Zhang, Jin-Sheng; Zhu, Qing; Ren, Jin-Ling; Yu, Yan-Rong; Liu, Xiu-Ying; Wang, Xiu-Jie; Han, Mei; Jing, Qing; Du, Jie; Tang, Chao-Shu; Qi, Yong-Fen

2018-06-26

Endoplasmic reticulum stress (ERS) is involved in the development of abdominal aortic aneurysm (AAA). Since bioactive peptide intermedin (IMD)1-53 protects against AAA formation, here we investigated whether IMD1-53 attenuates AAA by inhibiting ERS. AAA model was induced by angiotensin II (AngII) in ApoE KO mouse background. AngII-treated mouse aortas showed increased ERS gene transcription of caspase12, eukaryotic translation initiation factor 2a (eIf2a) and activating transcription factor 4(ATF4).The protein level of ERS marker glucose regulated protein 94(GRP94), ATF4 and C/EBP homologous protein 10(CHOP) was also up-regulated by AngII. Increased ERS levels were accompanied by severe VSMC apoptosis in human AAA aorta. In vivo administration of IMD1-53 greatly reduced AngII-induced AAA and abrogated the activation of ERS. To determine whether IMD inhibited AAA by ameliorating ERS, we used 2 non-selective ERS inhibitors phenyl butyrate (4-PBA) and taurine (TAU). Similar to IMD, PBA, and TAU significantly reduced the incidence of AAA and AAA-related pathological disorders. In vitro, AngII infusion up-regulated CHOP, caspase12 expression and led to VSMC apoptosis. IMD siRNA aggravated the CHOP, caspase12-mediated VSMC apoptosis, which was abolished by ATF4 silencing. IMD infusion promoted the phosphorylation of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) in aortas in ApoE KO mice, and the AMPK inhibitor compound C abolished the protective effect of IMD on VSMC ERS and apoptosis induced by AngII. In conclusion, IMD may protect against AAA formation by inhibiting ERS via activating AMPK phosphorylation.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheng, Lik Fai, E-mail: rickieclf@yahoo.com.hk; Cheung, Kwok Fai; Chan, Kwong Man

Nellix Endovascular Aneurysm Sealing (EVAS) system is a new concept and technology of abdominal aortic aneurysm (AAA) repair. Elective EVAS using Nellix device was performed for a 83-year-old man with AAA. 2-month post-EVAS CTA surveillance demonstrated mild enlargement of aneurysmal sac and separation of the EndoBags, but without detectable endoleak. The patient developed sudden AAA rupture with retroperitoneal hematoma at about 4 months after EVAS. We postulated that early enlargement of aneurysmal sac and separation of EndoBags of Nellix devices after EVAS, even without detectable endoleak, might indicate significant aneurysmal wall weakening with increased risk of later AAA rupture. To themore » best of the authors’ knowledge, this was the first reported case of aortic rupture after EVAS without detectable endoleak during and after the procedure.« less

Engineering Silicone Rubbers for In vitro Studies: Creating AAA Models and ILT Analogues with Physiological Properties

PubMed Central

Corbett, T.J.; Doyle, B.J.; Callanan, A.; Walsh, M.T.; McGloughlin, T.M

2010-01-01

Background In vitro studies of abdominal aortic aneurysm (AAA) have been widely reported. Frequently mock artery models with intraluminal thrombus (ILT) analogues are used to mimic the AAA in vivo. While the models used may be physiological, their properties are frequently either not reported or investigated. Method of Approach This study is concerned with the testing and characterisation of previously used vessel analogue materials and the development of new materials for the manufacture of AAA models. These materials were used in conjunction with a previously validated injection moulding technique to manufacture AAA models of ideal geometry. To determine the model properties (stiffness (β) and compliance) the diameter change of each AAA model was investigated under incrementally increasing internal pressures and compared to published in vivo studies to determine if the models behaved physiologically. A FEA study was implemented to determine if the pressure – diameter change behaviour of the models could be predicted numerically. ILT analogues were also manufactured and characterised. Ideal models were manufactured with ILT analogue internal to the aneurysm region and the effect of the ILT analogue on the model compliance and stiffness was investigated. Results The wall materials had similar properties to aortic tissue at physiological pressures (Einit 2.22MPa and 1.57MPa (aortic tissue: 1.8MPa)). ILT analogues had similar Young’s modulus to the medial layer of ILT (0.24 and 0.33MPa (ILT: 0.28MPa)). All models had aneurysm sac compliance in the physiological range (2.62 – 8.01×10-4/mmHg (AAA in vivo: 1.8 – 9.4×10-4/mmHg)). The necks of our AAA models had similar stiffness to healthy aortas (20.44 – 29.83 (healthy aortas in vivo: 17.5±5.5)). Good agreement was seen between the diameter changes due to pressurisation in the experimental and FEA wall models with a maximum error of 7.3% at 120mmHg. It was also determined that the inclusion of ILT analogue in the sac of our models could have an effect on the compliance of the model neck. Conclusions Ideal AAA models with physiological properties were manufactured. The behaviour of these models due to pressurisation was predicted using FEA, validating this technique for the future design of realistic, physiological AAA models. Addition of ILT analogues in the aneurysm sac was shown to affect neck behaviour. This could have implications for endovascular AAA repair due to the importance of the neck for stent-graft fixation. PMID:20524746

The incidence of incisional hernia after aortic aneurysm is not higher than after benign colorectal interventions: A retrospective control-matched cohort study.

PubMed

Wiegering, A; Liebetrau, D; Menzel, S; Bühler, C; Kellersmann, R; Dietz, U A

2018-01-01

Abdominal aortic aneurysms (AAA) have most probably an inflammatory origin, whereby the elastica is the layer actually involved. In the past, collagen weackness was supposed to be the shared cause of both, AAA and incisional hernias. Since the development of new techniques of closure of the abdominal wall over the last decade, collagen deficency seems to play only a secondary etiologic role. The aim of the study was to investigate whether the incidence of incisional hernia following laparotomy due to AAA differs from that of colorectal interventions. This was a retrospective control matched cohort study. After screening of 403 patients with colorectal interventions and 96 patients with AAA, 27 and 72 patients, respectively were included. The match criteria for inclusion of patients with colorectal interventions were: age, benign underlying disease and median xiphopubic laparotomy. The primary endpoint was the incidence of an incisional hernia. The secondary endpoints were the risk profile, length of stay in the intensive care unit and postoperative complications. Data analysis was carried in the consecutive collective from 2006 to 2008. In the group with AAA the mean follow-up was 34.5±18.1 months and in the group with colorectal interventions 35.7±21.4 months. The incidence of incisional hernias showed no significant differences between the two groups. In the AAA group 10 patients (13.8%) developed an incisional hernia in contrast to 7 patients in the colorectal intervention group (25.9%). In our collective patients with AAA did not show an increased incidence of incisional hernia in comparison to patients with colorectal interventions with comparable size of the laparotomy access and age. The quality of closure of the abdominal wall seems to be an important factor for the prevention of incisional hernia.

Vitamin D Receptor Activation Reduces Angiotensin-II-Induced Dissecting Abdominal Aortic Aneurysm in Apolipoprotein E-Knockout Mice.

PubMed

Martorell, Sara; Hueso, Luisa; Gonzalez-Navarro, Herminia; Collado, Aida; Sanz, Maria-Jesus; Piqueras, Laura

2016-08-01

Abdominal aortic aneurysm (AAA) is a vascular disorder characterized by chronic inflammation of the aortic wall. Low concentrations of vitamin D3 are associated with AAA development; however, the potential direct effect of vitamin D3 on AAA remains unknown. This study evaluates the effect of oral treatment with the vitamin D3 receptor (VDR) ligand, calcitriol, on dissecting AAA induced by angiotensin-II (Ang-II) infusion in apoE(-/-) mice. Oral treatment with calcitriol reduced Ang-II-induced dissecting AAA formation in apoE(-/-) mice, which was unrelated to systolic blood pressure or plasma cholesterol concentrations. Immunohistochemistry and reverse-transcription polymerase chain reaction analysis demonstrated a significant increase in macrophage infiltration, neovessel formation, matrix metalloproteinase-2 and matrix metalloproteinase-9, chemokine (CCL2 [(C-C motif) ligand 2], CCL5 [(C-C motif) ligand 5], and CXCL1 [(C-X-C motif) ligand 1]) and vascular endothelial growth factor expression in suprarenal aortic walls of apoE(-/-) mice infused with Ang-II, and all were significantly reduced by cotreatment with calcitriol. Phosphorylation of extracellular signal-regulated kinases 1/2, p38 mitogen-activated protein kinase, and nuclear factor-κB was also decreased in the suprarenal aortas of apoE(-/-) mice cotreated with calcitriol. These effects were accompanied by a marked increase in VDR-retinoid X receptor (RXR) interaction in the aortas of calcitriol-treated mice. In vitro, VDR activation by calcitriol in human endothelial cells inhibited Ang-II-induced leukocyte-endothelial cell interactions, morphogenesis, and production of endothelial proinflammatory and angiogenic chemokines through VDR-RXR interactions, and knockdown of VDR or RXR abolished the inhibitory effects of calcitriol. VDR activation reduces dissecting AAA formation induced by Ang-II in apoE(-/-) mice and may constitute a novel therapeutic strategy to prevent AAA progression. © 2016 American Heart Association, Inc.

Redox proteomic analysis of serum from aortic anerurysm patients: insights on oxidation of specific protein target.

PubMed

Spadaccio, Cristiano; Coccia, Raffaella; Perluigi, Marzia; Pupo, Gilda; Schininà, Maria Eugenia; Giorgi, Alessandra; Blarzino, Carla; Nappi, Francesco; Sutherland, Fraser W; Chello, Massimo; Di Domenico, Fabio

2016-06-21

oxidative stress is undoubtedly one of the main players in abdominal aortic aneurysm (AAA) pathophysiology. Recent studies in AAA patients reported an increase in the indices of oxidative damage at the tissue level and in biological fluids coupled with the loss of counter-regulatory mechanisms of protection from oxidative stress. We recently reported, in a proteomic analysis of AAA patient sera, changes in the expression of several proteins exerting important modulatory activities on cellular proliferation, differentiation and response to damage. This study aimed to explore the involvement of protein oxidation, at peripheral levels, in AAA. a redox proteomic approach was used to investigate total and specific protein carbonylation and protein-bound 4-hydroxy-2-nonenal (HNE) in the serum of AAA patients compared with age-matched controls. our results show increased oxidative damage to protein as indexed by the total carbonyl levels and total protein-bound HNE. By redox proteomics we identified specific carbonylation of three serum proteins: serum retinol-binding protein, vitamin D-binding protein and fibrinogen α-chain HNE. We also identified increased protein-bound HNE levels for hemopexin, IgK chain C region and IgK chain V-III region SIE. In addition we found a high correlation between specific protein carbonylation and protein-bound HNE and the aortic diameter. Moreover the analysis of serum proteins with antioxidant activity demonstrates the oxidation of albumin together with the overexpression of transferrin, haptoglobin and HSPs 90, 70, 60 and 32. this study support the involvement of oxidative stress in the pathogenesis of AAA and might provide a further degree of knowledge in the cause-effect role of oxidative stress shedding new light on the molecular candidates involved in the disease.

Combining two potential causes of metalloproteinase secretion causes abdominal aortic aneurysms in rats: a new experimental model

PubMed Central

Mata, Karina M; Prudente, Paula S; Rocha, Fabio S; Prado, Cibele M; Floriano, Elaine M; Elias, Jorge; Rizzi, Elen; Gerlach, Raquel F; Rossi, Marcos A; Ramos, Simone G

2011-01-01

Progress in understanding the pathophysiology of abdominal aortic aneurysms (AAA) is dependent in part on the development and application of effective animal models that recapitulate key aspects of the disease. The objective was to produce an experimental model of AAA in rats by combining two potential causes of metalloproteinase (MMP) secretion: inflammation and turbulent blood flow. Male Wistar rats were randomly divided in four groups: Injury, Stenosis, Aneurysm and Control (40/group). The Injury group received a traumatic injury to the external aortic wall. The Stenosis group received an extrinsic stenosis at a corresponding location. The Aneurysm group received both the injury and stenosis simultaneously, and the Control group received a sham operation. Animals were euthanized at days 1, 3, 7 and 15. Aorta and/or aneurysms were collected and the fragments were fixed for morphologic, immunohistochemistry and morphometric analyses or frozen for MMP assays. AAAs had developed by day 3 in 60–70% of the animals, reaching an aortic dilatation ratio of more than 300%, exhibiting intense wall remodelling initiated at the adventitia and characterized by an obvious inflammatory infiltrate, mesenchymal proliferation, neoangiogenesis, elastin degradation and collagen deposition. Immunohistochemistry and zymography studies displayed significantly increased expressions of MMP-2 and MMP-9 in aneurysm walls compared to other groups. The haemo-dynamic alterations caused by the stenosis may have provided additional contribution to the MMPs liberation. This new model illustrated that AAA can be multifactorial and confirmed the key roles of MMP-2 and MMP-9 in this dynamic remodelling process. PMID:21039990

Association between osteopontin and human abdominal aortic aneurysm.

PubMed

Golledge, Jonathan; Muller, Juanita; Shephard, Neil; Clancy, Paula; Smallwood, Linda; Moran, Corey; Dear, Anthony E; Palmer, Lyle J; Norman, Paul E

2007-03-01

In vitro and animal studies have implicated osteopontin (OPN) in the pathogenesis of aortic aneurysm. The relationship between serum concentration of OPN and variants of the OPN gene with human abdominal aortic aneurysm (AAA) was investigated. OPN genotypes were examined in 4227 subjects in which aortic diameter and clinical risk factors were measured. Serum OPN was measured by ELISA in two cohorts of 665 subjects. The concentration of serum OPN was independently associated with the presence of AAA. Odds ratios (and 95% confidence intervals) for upper compared with lower OPN tertiles in predicting presence of AAA were 2.23 (1.29 to 3.85, P=0.004) for the population cohort and 4.08 (1.67 to 10.00, P=0.002) for the referral cohort after adjusting for other risk factors. In 198 patients with complete follow-up of aortic diameter at 3 years, initial serum OPN predicted AAA growth after adjustment for other risk factors (standardized coefficient 0.24, P=0.001). The concentration of OPN in the aortic wall was greater in patients with small AAAs (30 to 50 mm) than those with aortic occlusive disease alone. There was no association between five single nucleotide polymorphisms or haplotypes of the OPN gene and aortic diameter or AAA expansion. Serum and tissue concentrations of OPN are associated with human AAA. We found no relationship between variation of the OPN gene and AAA. OPN may be a useful biomarker for AAA presence and growth.

Loss of Drosophila i-AAA protease, dYME1L, causes abnormal mitochondria and apoptotic degeneration.

PubMed

Qi, Y; Liu, H; Daniels, M P; Zhang, G; Xu, H

2016-02-01

Mitochondrial AAA (ATPases Associated with diverse cellular Activities) proteases i-AAA (intermembrane space-AAA) and m-AAA (matrix-AAA) are closely related and have major roles in inner membrane protein homeostasis. Mutations of m-AAA proteases are associated with neuromuscular disorders in humans. However, the role of i-AAA in metazoans is poorly understood. We generated a deletion affecting Drosophila i-AAA, dYME1L (dYME1L(del)). Mutant flies exhibited premature aging, progressive locomotor deficiency and neurodegeneration that resemble some key features of m-AAA diseases. dYME1L(del) flies displayed elevated mitochondrial unfolded protein stress and irregular cristae. Aged dYME1L(del) flies had reduced complex I (NADH/ubiquinone oxidoreductase) activity, increased level of reactive oxygen species (ROS), severely disorganized mitochondrial membranes and increased apoptosis. Furthermore, inhibiting apoptosis by targeting dOmi (Drosophila Htra2/Omi) or DIAP1, or reducing ROS accumulation suppressed retinal degeneration. Our results suggest that i-AAA is essential for removing unfolded proteins and maintaining mitochondrial membrane architecture. Loss of i-AAA leads to the accumulation of oxidative damage and progressive deterioration of membrane integrity, which might contribute to apoptosis upon the release of proapoptotic molecules such as dOmi. Containing ROS level could be a potential strategy to manage mitochondrial AAA protease deficiency.

Early Enlargement of Aneurysmal Sac and Separation of EndoBags of Nellix Endovascular Aneurysm Sealing System as Signs of Increased Risk of Later Aneurysm Rupture.

PubMed

Cheng, Lik Fai; Cheung, Kwok Fai; Chan, Kwong Man; Ma, Johnny Ka Fai; Luk, Wing Hang; Chan, Micah Chi King; Ng, Carol Wing Kei; Mahboobani, Neeraj Ramesh; Ng, Wai Kin; Wong, Ting

2016-11-01

Nellix Endovascular Aneurysm Sealing (EVAS) system is a new concept and technology of abdominal aortic aneurysm (AAA) repair. Elective EVAS using Nellix device was performed for a 83-year-old man with AAA. 2-month post-EVAS CTA surveillance demonstrated mild enlargement of aneurysmal sac and separation of the EndoBags, but without detectable endoleak. The patient developed sudden AAA rupture with retroperitoneal hematoma at about 4 months after EVAS. We postulated that early enlargement of aneurysmal sac and separation of EndoBags of Nellix devices after EVAS, even without detectable endoleak, might indicate significant aneurysmal wall weakening with increased risk of later AAA rupture. To the best of the authors' knowledge, this was the first reported case of aortic rupture after EVAS without detectable endoleak during and after the procedure.

Sugarcane transcriptome analysis in response to infection caused by Acidovorax avenae subsp. avenae

PubMed Central

Grativol, Clícia; de Armas, Elvismary M.; Entenza, Júlio O. P.; Thiebaut, Flávia; Lima, Marcelo de F.; Farrinelli, Laurent; Hemerly, Adriana S.; Lifschitz, Sérgio; Ferreira, Paulo C. G.

2016-01-01

Sugarcane is an important tropical crop mainly cultivated to produce ethanol and sugar. Crop productivity is negatively affected by Acidovorax avenae subsp avenae (Aaa), which causes the red stripe disease. Little is known about the molecular mechanisms triggered in response to the infection. We have investigated the molecular mechanism activated in sugarcane using a RNA-seq approach. We have produced a de novo transcriptome assembly (TR7) from sugarcane RNA-seq libraries submitted to drought and infection with Aaa. Together, these libraries present 247 million of raw reads and resulted in 168,767 reference transcripts. Mapping in TR7 of reads obtained from infected libraries, revealed 798 differentially expressed transcripts, of which 723 were annotated, corresponding to 467 genes. GO and KEGG enrichment analysis showed that several metabolic pathways, such as code for proteins response to stress, metabolism of carbohydrates, processes of transcription and translation of proteins, amino acid metabolism and biosynthesis of secondary metabolites were significantly regulated in sugarcane. Differential analysis revealed that genes in the biosynthetic pathways of ET and JA PRRs, oxidative burst genes, NBS-LRR genes, cell wall fortification genes, SAR induced genes and pathogenesis-related genes (PR) were upregulated. In addition, 20 genes were validated by RT-qPCR. Together, these data contribute to a better understanding of the molecular mechanisms triggered by the Aaa in sugarcane and opens the opportunity for the development of molecular markers associated with disease tolerance in breeding programs. PMID:27936012

Sugarcane transcriptome analysis in response to infection caused by Acidovorax avenae subsp. avenae.

PubMed

Santa Brigida, Ailton B; Rojas, Cristian A; Grativol, Clícia; de Armas, Elvismary M; Entenza, Júlio O P; Thiebaut, Flávia; Lima, Marcelo de F; Farrinelli, Laurent; Hemerly, Adriana S; Lifschitz, Sérgio; Ferreira, Paulo C G

2016-01-01

Sugarcane is an important tropical crop mainly cultivated to produce ethanol and sugar. Crop productivity is negatively affected by Acidovorax avenae subsp avenae (Aaa), which causes the red stripe disease. Little is known about the molecular mechanisms triggered in response to the infection. We have investigated the molecular mechanism activated in sugarcane using a RNA-seq approach. We have produced a de novo transcriptome assembly (TR7) from sugarcane RNA-seq libraries submitted to drought and infection with Aaa. Together, these libraries present 247 million of raw reads and resulted in 168,767 reference transcripts. Mapping in TR7 of reads obtained from infected libraries, revealed 798 differentially expressed transcripts, of which 723 were annotated, corresponding to 467 genes. GO and KEGG enrichment analysis showed that several metabolic pathways, such as code for proteins response to stress, metabolism of carbohydrates, processes of transcription and translation of proteins, amino acid metabolism and biosynthesis of secondary metabolites were significantly regulated in sugarcane. Differential analysis revealed that genes in the biosynthetic pathways of ET and JA PRRs, oxidative burst genes, NBS-LRR genes, cell wall fortification genes, SAR induced genes and pathogenesis-related genes (PR) were upregulated. In addition, 20 genes were validated by RT-qPCR. Together, these data contribute to a better understanding of the molecular mechanisms triggered by the Aaa in sugarcane and opens the opportunity for the development of molecular markers associated with disease tolerance in breeding programs.

Characterization of the Modular Design of the Autolysin/Adhesin Aaa from Staphylococcus Aureus

PubMed Central

Hirschhausen, Nina; Schlesier, Tim; Peters, Georg; Heilmann, Christine

2012-01-01

Background Staphylococcus aureus is a frequent cause of serious and life-threatening infections, such as endocarditis, osteomyelitis, pneumonia, and sepsis. Its adherence to various host structures is crucial for the establishment of diseases. Adherence may be mediated by a variety of adhesins, among them the autolysin/adhesins Atl and Aaa. Aaa is composed of three N-terminal repeated sequences homologous to a lysin motif (LysM) that can confer cell wall attachment and a C-terminally located cysteine, histidine-dependent amidohydrolase/peptidase (CHAP) domain having bacteriolytic activity in many proteins. Methodology/Principal Findings Here, we show by surface plasmon resonance that the LysM domain binds to fibrinogen, fibronectin, and vitronectin respresenting a novel adhesive function for this domain. Moreover, we demonstrated that the CHAP domain not only mediates the bacteriolytic activity, but also adherence to fibrinogen, fibronectin, and vitronectin, thus demonstrating for the first time an adhesive function for this domain. Adherence of an S. aureus aaa mutant and the complemented aaa mutant is slightly decreased and increased, respectively, to vitronectin, but not to fibrinogen and fibronectin, which might at least in part result from an increased expression of atl in the aaa mutant. Furthermore, an S. aureus atl mutant that showed enhanced adherence to fibrinogen, fibronectin, and endothelial cells also demonstrated increased aaa expression and production of Aaa. Thus, the redundant functions of Aaa and Atl might at least in part be interchangeable. Lastly, RT-PCR and zymographic analysis revealed that aaa is negatively regulated by the global virulence gene regulators agr and SarA. Conclusions/Significance We identified novel functions for two widely distributed protein domains, LysM and CHAP, i.e. the adherence to the extracellular matrix proteins fibrinogen, fibronectin, and vitronectin. The adhesive properties of Aaa might promote S. aureus colonization of host extracellular matrix and tissue, suggesting a role for Aaa in the pathogenesis of S. aureus infections. PMID:22768285

Characterization of the modular design of the autolysin/adhesin Aaa from Staphylococcus aureus.

PubMed

Hirschhausen, Nina; Schlesier, Tim; Peters, Georg; Heilmann, Christine

2012-01-01

Staphylococcus aureus is a frequent cause of serious and life-threatening infections, such as endocarditis, osteomyelitis, pneumonia, and sepsis. Its adherence to various host structures is crucial for the establishment of diseases. Adherence may be mediated by a variety of adhesins, among them the autolysin/adhesins Atl and Aaa. Aaa is composed of three N-terminal repeated sequences homologous to a lysin motif (LysM) that can confer cell wall attachment and a C-terminally located cysteine, histidine-dependent amidohydrolase/peptidase (CHAP) domain having bacteriolytic activity in many proteins. Here, we show by surface plasmon resonance that the LysM domain binds to fibrinogen, fibronectin, and vitronectin respresenting a novel adhesive function for this domain. Moreover, we demonstrated that the CHAP domain not only mediates the bacteriolytic activity, but also adherence to fibrinogen, fibronectin, and vitronectin, thus demonstrating for the first time an adhesive function for this domain. Adherence of an S. aureus aaa mutant and the complemented aaa mutant is slightly decreased and increased, respectively, to vitronectin, but not to fibrinogen and fibronectin, which might at least in part result from an increased expression of atl in the aaa mutant. Furthermore, an S. aureus atl mutant that showed enhanced adherence to fibrinogen, fibronectin, and endothelial cells also demonstrated increased aaa expression and production of Aaa. Thus, the redundant functions of Aaa and Atl might at least in part be interchangeable. Lastly, RT-PCR and zymographic analysis revealed that aaa is negatively regulated by the global virulence gene regulators agr and SarA. We identified novel functions for two widely distributed protein domains, LysM and CHAP, i.e. the adherence to the extracellular matrix proteins fibrinogen, fibronectin, and vitronectin. The adhesive properties of Aaa might promote S. aureus colonization of host extracellular matrix and tissue, suggesting a role for Aaa in the pathogenesis of S. aureus infections.

Effects of osteoprotegerin/TNFRSF11B in two models of abdominal aortic aneurysms.

PubMed

Vorkapic, Emina; Kunath, Anne; Wågsäter, Dick

2018-04-27

Osteoprotegerin (OPG), additionally termed tumor necrosis factor receptor superfamily member 11B, is produced by vascular smooth muscle cells (VSMCs) and endothelial cells in the vasculature, and its release may be modulated by pro‑inflammatory cytokines, including interleukin‑1β and tumor necrosis factor‑α. The present study investigated the effects of treatment with low‑dose human recombinant OPG on abdominal aortic aneurysm (AAA) development in mice. Mice were treated with 1 µg human recombinant OPG four times (or vehicle) for 2 weeks prior to inducing AAA. A total of two different models for inducing AAA were used to investigate the hypothesis as to whether OPG is involved in key events of AAA development, using osmotic mini‑pumps with angiotensin II in apolipoprotein‑E (ApoE‑/‑) mice for 28 days or using periaortic application of CaCl2 on the aorta in C57Bl/6J mice for 14 days. OPG was continuously administered during the experimental period. Histological staining using Masson's trichrome, Verhoeff's van‑Gieson and picro‑sirius red, in addition to reverse transcription‑quantitative polymerase chain reaction analysis of various markers, were used to analyze phenotypic alterations. Treatment with OPG had no inhibitory effect on AAA development in the angiotensin II model in ApoE‑/‑ mice, which developed suprarenal aneurysms, although it increased vessel wall thickness of the aorta and total collagen in C57Bl/6J mice using the CaCl2 model that induced infrarenal dilation of the aorta. Treatment with OPG did not inhibit aneurysm development and key events, including inflammation, extracellular matrix or VSMC remodeling, in aortas from OPG‑treated mice with periaortic treatment with CaCl2. The results indicated that mice treated with low levels of human recombinant OPG may have a more stable aneurysmal phenotype due to compensatory production of collagen and increased vessel wall thickness of the aorta, potentially protecting the aneurysm from rupture. Further studies investigating rupture models of AAA in addition to using higher levels of OPG are require to verify this speculation. Furthermore, treatment with low levels of OPG in patients with AAA may represent a novel therapeutic strategy for the treatment of AAA as well as attenuate the adverse effects associated with the administration of normal and high dosages of OPG.

3D analysis of vortical structures in an abdominal aortic aneurysm by stereoscopic PIV

NASA Astrophysics Data System (ADS)

Deplano, Valérie; Guivier-Curien, Carine; Bertrand, Eric

2016-11-01

The present work presents an experimental in vitro three-dimensional analysis of the flow dynamics in an abdominal aortic aneurysm (AAA) through stereoscopic particle image velocimetry (SPIV) measurements. The experimental set-up mimics the pathophysiological context involving a shear thinning blood analogue fluid, compliant AAA and aorto-iliac bifurcation walls and controlled inlet and outlet flow rate and pressure waveforms as well as working fluid temperature. SPIV was carefully calibrated and conducted to assess the three velocity components in the AAA volume. For the first time in the literature, the 3D vortex ring genesis, propagation, and vanishing in the AAA bulge are experimentally described and quantified. In comparison with classical 2-component PIV measurements (2C PIV), the third component of the velocity vector was shown to be of importance in such a geometry, especially, during the deceleration phase of the flow rate. The 3D velocity magnitude reached up more than 20 % of the 2D one showing that 2C PIV are definitively not accurate enough to provide a complete description of flow behaviour in an AAA. In addition to potential clinical implications of a full 3D vortex ring description in AAA evolution, the 3D in vitro experimental quantification of the flow dynamics carried out in the present study offers an interesting tool for the validation of fluid-structure interaction numerical studies dealing with AAA.

The interleukin-10-1082 'A' allele and abdominal aortic aneurysms.

PubMed

Bown, Matthew J; Lloyd, Geraint M; Sandford, Rebecca M; Thompson, John R; London, Nicholas J M; Samani, Nilesh J; Sayers, Robert D

2007-10-01

Abdominal aortic aneurysms (AAA) are caused by inflammatory processes in the wall of the aorta resulting in degradation of structural proteins. This inflammatory process is mediated, in part, by cytokines, and interleukin-10 (IL-10) is a predominantly anti-inflammatory cytokine. A single nucleotide polymorphism in the promoter region of the IL-10 gene that affects transcription has been associated with AAA in a small study. The aim of this study was to determine whether this polymorphism is associated with AAA and also examine its effect on the growth of small AAA. A case control study was performed. A total of 389 patients with AAA and 404 healthy controls were recruited. IL-10-1082 polymorphisms were determined by polymerase chain reaction-based methods. In the case of patients with small AAA (<5.5 cm), serial size measurements were recorded to determine mean growth rate. There was a statistically significant difference both in allele and genotype frequencies between the case and control groups with the IL-10-1082 'A' allele being more common in the AAA group (P = .006). In the AAA group, genotype frequencies were as follows: GG 84, GA 201, and AA 104. In the control group, the genotype frequencies were GG 118, GA 205, and AA 81. The odds ratio for the 'A' allele as a risk factor for AAA was 1.50 (95% confidence interval 1.09 to 2.07). Regression modeling revealed that the IL-10-1082 genotype was, however, not independently associated with AAA if age, tobacco use, hypertension, and history of coronary or peripheral artery disease was taken into account. There was a trend towards lower plasma IL-10 level in IL-10 AA carriers, but the IL-10 'A' allele did not have any discernible effect on the growth of small AAA. This study demonstrates that the IL-10-1082 'A' allele is associated with AAA, although this association is likely to be secondary to an association between IL-10-1082 genotype and other markers of cardiovascular disease rather than AAA per se.

The Abdominal Aortic Aneurysm and Intraluminal Thrombus: Current Concepts of Development and Treatment

PubMed Central

Piechota-Polanczyk, Aleksandra; Jozkowicz, Alicja; Nowak, Witold; Eilenberg, Wolf; Neumayer, Christoph; Malinski, Tadeusz; Huk, Ihor; Brostjan, Christine

2015-01-01

The pathogenesis of the abdominal aortic aneurysm (AAA) shows several hallmarks of atherosclerotic and atherothrombotic disease, but comprises an additional, predominant feature of proteolysis resulting in the degradation and destabilization of the aortic wall. This review aims to summarize the current knowledge on AAA development, involving the accumulation of neutrophils in the intraluminal thrombus and their central role in creating an oxidative and proteolytic environment. Particular focus is placed on the controversial role of heme oxygenase 1/carbon monoxide and nitric oxide synthase/peroxynitrite, which may exert both protective and damaging effects in the development of the aneurysm. Treatment indications as well as surgical and pharmacological options for AAA therapy are discussed in light of recent reports. PMID:26664891

Role of Interleukin-1 Signaling in a Mouse Model of Kawasaki Disease-Associated Abdominal Aortic Aneurysm.

PubMed

Wakita, Daiko; Kurashima, Yosuke; Crother, Timothy R; Noval Rivas, Magali; Lee, Youngho; Chen, Shuang; Fury, Wen; Bai, Yu; Wagner, Shawn; Li, Debiao; Lehman, Thomas; Fishbein, Michael C; Hoffman, Hal M; Shah, Prediman K; Shimada, Kenichi; Arditi, Moshe

2016-05-01

Kawasaki disease (KD) is the most common cause of acquired cardiac disease in US children. In addition to coronary artery abnormalities and aneurysms, it can be associated with systemic arterial aneurysms. We evaluated the development of systemic arterial dilatation and aneurysms, including abdominal aortic aneurysm (AAA) in the Lactobacillus casei cell-wall extract (LCWE)-induced KD vasculitis mouse model. We discovered that in addition to aortitis, coronary arteritis and myocarditis, the LCWE-induced KD mouse model is also associated with abdominal aorta dilatation and AAA, as well as renal and iliac artery aneurysms. AAA induced in KD mice was exclusively infrarenal, both fusiform and saccular, with intimal proliferation, myofibroblastic proliferation, break in the elastin layer, vascular smooth muscle cell loss, and inflammatory cell accumulation in the media and adventitia. Il1r(-/-), Il1a(-/-), and Il1b(-/-) mice were protected from KD associated AAA. Infiltrating CD11c(+) macrophages produced active caspase-1, and caspase-1 or NLRP3 deficiency inhibited AAA formation. Treatment with interleukin (IL)-1R antagonist (Anakinra), anti-IL-1α, or anti-IL-1β mAb blocked LCWE-induced AAA formation. Similar to clinical KD, the LCWE-induced KD vasculitis mouse model can also be accompanied by AAA formation. Both IL-1α and IL-1β play a key role, and use of an IL-1R blocking agent that inhibits both pathways may be a promising therapeutic target not only for KD coronary arteritis, but also for the other systemic arterial aneurysms including AAA that maybe seen in severe cases of KD. The LCWE-induced vasculitis model may also represent an alternative model for AAA disease. © 2016 American Heart Association, Inc.

Chinese Herbal Medicine as a Potential Treatment of Abdominal Aortic Aneurysm

PubMed Central

Seto, Sai Wang; Chang, Dennis; Kiat, Hosen; Wang, Ning; Bensoussan, Alan

2018-01-01

Abdominal aortic aneurysm (AAA) is an irreversible condition where the abdominal aorta is dilated leading to potentially fatal consequence of aortic rupture. Multiple mechanisms are involved in the development and progression of AAA, including chronic inflammation, oxidative stress, vascular smooth muscle (VSMC) apoptosis, immune cell infiltration and extracellular matrix (ECM) degradation. Currently surgical therapies, including minimally invasive endovascular aneurysm repair (EVAR), are the only viable interventions for AAAs. However, these treatments are not appropriate for the majority of AAAs, which measure <50 mm. Substantial effort has been invested to identify and develop pharmaceutical treatments such as statins and doxycycline for this potentially lethal condition but these interventions failed to offer a cure or to retard the progression of AAA. Chinese herbal medicine (CHM) has been used for the management of cardiovascular diseases for thousands of years in China and other Asian countries. The unique multi-component and multi-target property of CHMs makes it a potentially ideal therapy for multifactorial diseases such as AAA. In this review, we review the current scientific evidence to support the use of CHMs for the treatment of AAA. Mechanisms of action underlying the effects of CHMs on AAA are also discussed. PMID:29732374

Chinese Herbal Medicine as a Potential Treatment of Abdominal Aortic Aneurysm.

PubMed

Seto, Sai Wang; Chang, Dennis; Kiat, Hosen; Wang, Ning; Bensoussan, Alan

2018-01-01

Abdominal aortic aneurysm (AAA) is an irreversible condition where the abdominal aorta is dilated leading to potentially fatal consequence of aortic rupture. Multiple mechanisms are involved in the development and progression of AAA, including chronic inflammation, oxidative stress, vascular smooth muscle (VSMC) apoptosis, immune cell infiltration and extracellular matrix (ECM) degradation. Currently surgical therapies, including minimally invasive endovascular aneurysm repair (EVAR), are the only viable interventions for AAAs. However, these treatments are not appropriate for the majority of AAAs, which measure <50 mm. Substantial effort has been invested to identify and develop pharmaceutical treatments such as statins and doxycycline for this potentially lethal condition but these interventions failed to offer a cure or to retard the progression of AAA. Chinese herbal medicine (CHM) has been used for the management of cardiovascular diseases for thousands of years in China and other Asian countries. The unique multi-component and multi-target property of CHMs makes it a potentially ideal therapy for multifactorial diseases such as AAA. In this review, we review the current scientific evidence to support the use of CHMs for the treatment of AAA. Mechanisms of action underlying the effects of CHMs on AAA are also discussed.

Abdominal Aortic Aneurysm (AAA)

MedlinePlus

... plaque buildup causes the walls of the abdominal aorta to become weak and bulge outward like a ... treated? What is an abdominal aortic aneurysm? The aorta, the largest artery in the body, is a ...

Pulse wave imaging in normal, hypertensive and aneurysmal human aortas in vivo: a feasibility study

NASA Astrophysics Data System (ADS)

Li, Ronny X.; Luo, Jianwen; Balaram, Sandhya K.; Chaudhry, Farooq A.; Shahmirzadi, Danial; Konofagou, Elisa E.

2013-07-01

Arterial stiffness is a well-established biomarker for cardiovascular risk, especially in the case of hypertension. The progressive stages of an abdominal aortic aneurysm (AAA) have also been associated with varying arterial stiffness. Pulse wave imaging (PWI) is a noninvasive, ultrasound imaging-based technique that uses the pulse wave-induced arterial wall motion to map the propagation of the pulse wave and measure the regional pulse wave velocity (PWV) as an index of arterial stiffness. In this study, the clinical feasibility of PWI was evaluated in normal, hypertensive, and aneurysmal human aortas. Radiofrequency-based speckle tracking was used to estimate the pulse wave-induced displacements in the abdominal aortic walls of normal (N = 15, mean age 32.5 ± 10.2 years), hypertensive (N = 13, mean age 60.8 ± 15.8 years), and aneurysmal (N = 5, mean age 71.6 ± 11.8 years) human subjects. Linear regression of the spatio-temporal variation of the displacement waveform in the anterior aortic wall over a single cardiac cycle yielded the slope as the PWV and the coefficient of determination r2 as an approximate measure of the pulse wave propagation uniformity. The aortic PWV measurements in all normal, hypertensive, and AAA subjects were 6.03 ± 1.68, 6.69 ± 2.80, and 10.54 ± 6.52 m s-1, respectively. There was no significant difference (p = 0.15) between the PWVs of the normal and hypertensive subjects while the PWVs of the AAA subjects were significantly higher (p < 0.001) compared to those of the other two groups. Also, the average r2 in the AAA subjects was significantly lower (p < 0.001) than that in the normal and hypertensive subjects. These preliminary results suggest that the regional PWV and the pulse wave propagation uniformity (r2) obtained using PWI, in addition to the PWI images and spatio-temporal maps that provide qualitative visualization of the pulse wave, may potentially provide valuable information for the clinical characterization of aneurysms and other vascular pathologies that regionally alter the arterial wall mechanics.

Structure, Mechanics, and Histology of Intraluminal Thrombi in Abdominal Aortic Aneurysms.

PubMed

Tong, Jianhua; Holzapfel, Gerhard A

2015-07-01

It has been recognized that the intraluminal thrombus (ILT) is a biologically active material contributing in the progression and rupture of abdominal aortic aneurysms (AAAs). To advance our understanding of the potential role of ILT in the natural history of AAAs, the structural, mechanical, and histological characteristics of ILTs have been studied with great interest over the past decade. Given that the ILT is evolving and changing its composition during AAA progression, attention has been paid to exploring the chemomechanical effects of ILT on the underlying wall properties. Various biomechanical and chemomechanical data, and related models have provided advanced insights into AAA pathogenesis which have served as a basis for clinical diagnosis. The goal of this review is to describe and summarize recent advances in the research of ILT found in the aorta in terms of structure, mechanics, and histology on a patient-specific basis. We point to some possible future studies which hopefully stimulate multidisciplinary research to address open problems.

The effect of flow recirculation on abdominal aortic aneurysm

NASA Astrophysics Data System (ADS)

Taib, Ishkrizat; Amirnordin, Shahrin Hisham; Madon, Rais Hanizam; Mustafa, Norrizal; Osman, Kahar

2012-06-01

The presences of flow recirculation at the abdominal aortic aneurysm (AAA) region yield the unpredictable failure of aneurismal wall. The failure of the aneurismal wall is closely related to the hemodynamic factor. Hemodynamic factor such as pressure and velocity distribution play a significance role of aneurysm growth and rupture. By using the computational approach, the influence of hemodynamic factor is investigated using computational fluid dynamic (CFD) method on the virtual AAA model. The virtual 3D AAAs model was reconstructed from Spiral Computed Tomography scan (CT-scan). The blood flow is assumed as being transient, laminar and Newtonian within a rigid section of the vessel. The blood flow also driven by an imposed of pressure gradient in the form of physiological waveform. The pulsating blood flow is also considered in this simulation. The results on pressure distribution and velocity profile are analyzed to interpret the behaviour of flow recirculation. The results show the forming of vortices is seen at the aneurysm bulge. This vortices is form at the aneurysm region then destroyed rapidly by flow recirculation. Flow recirculation is point out much higher at distal end of aneurysm closed to iliac bifurcation. This phenomenon is managed to increase the possibility of aneurysm growth and rupture.

Nanoparticles Effectively Target Rapamycin Delivery to Sites of Experimental Aortic Aneurysm in Rats.

PubMed

Shirasu, Takuro; Koyama, Hiroyuki; Miura, Yutaka; Hoshina, Katsuyuki; Kataoka, Kazunori; Watanabe, Toshiaki

2016-01-01

Several drugs targeting the pathogenesis of aortic aneurysm have shown efficacy in model systems but not in clinical trials, potentially owing to the lack of targeted drug delivery. Here, we designed a novel drug delivery system using nanoparticles to target the disrupted aortic aneurysm micro-structure. We generated poly(ethylene glycol)-shelled nanoparticles incorporating rapamycin that exhibited uniform diameter and long-term stability. When injected intravenously into a rat model in which abdominal aortic aneurysm (AAA) had been induced by infusing elastase, labeled rapamycin nanoparticles specifically accumulated in the AAA. Microscopic analysis revealed that rapamycin nanoparticles were mainly distributed in the media and adventitia where the wall structures were damaged. Co-localization of rapamycin nanoparticles with macrophages was also noted. Rapamycin nanoparticles injected during the process of AAA formation evinced significant suppression of AAA formation and mural inflammation at 7 days after elastase infusion, as compared with rapamycin treatment alone. Correspondingly, the activities of matrix metalloproteinases and the expression of inflammatory cytokines were significantly suppressed by rapamycin nanoparticle treatment. Our findings suggest that the nanoparticle-based delivery system achieves specific delivery of rapamycin to the rat AAA and might contribute to establishing a drug therapy approach targeting aortic aneurysm.

Nanoparticles Effectively Target Rapamycin Delivery to Sites of Experimental Aortic Aneurysm in Rats

PubMed Central

Shirasu, Takuro; Koyama, Hiroyuki; Miura, Yutaka; Hoshina, Katsuyuki; Kataoka, Kazunori; Watanabe, Toshiaki

2016-01-01

Several drugs targeting the pathogenesis of aortic aneurysm have shown efficacy in model systems but not in clinical trials, potentially owing to the lack of targeted drug delivery. Here, we designed a novel drug delivery system using nanoparticles to target the disrupted aortic aneurysm micro-structure. We generated poly(ethylene glycol)-shelled nanoparticles incorporating rapamycin that exhibited uniform diameter and long-term stability. When injected intravenously into a rat model in which abdominal aortic aneurysm (AAA) had been induced by infusing elastase, labeled rapamycin nanoparticles specifically accumulated in the AAA. Microscopic analysis revealed that rapamycin nanoparticles were mainly distributed in the media and adventitia where the wall structures were damaged. Co-localization of rapamycin nanoparticles with macrophages was also noted. Rapamycin nanoparticles injected during the process of AAA formation evinced significant suppression of AAA formation and mural inflammation at 7 days after elastase infusion, as compared with rapamycin treatment alone. Correspondingly, the activities of matrix metalloproteinases and the expression of inflammatory cytokines were significantly suppressed by rapamycin nanoparticle treatment. Our findings suggest that the nanoparticle-based delivery system achieves specific delivery of rapamycin to the rat AAA and might contribute to establishing a drug therapy approach targeting aortic aneurysm. PMID:27336852

Vitamin E Inhibits Abdominal Aortic Aneurysm Formation in Angiotensin II–Infused Apolipoprotein E–Deficient Mice

PubMed Central

Gavrila, Dan; Li, Wei Gen; McCormick, Michael L.; Thomas, Manesh; Daugherty, Alan; Cassis, Lisa A.; Miller, Francis J.; Oberley, Larry W.; Dellsperger, Kevin C.; Weintraub, Neal L.

2014-01-01

Background Abdominal aortic aneurysms (AAAs) in humans are associated with locally increased oxidative stress and activity of NADPH oxidase. We investigated the hypothesis that vitamin E, an antioxidant with documented efficacy in mice, can attenuate AAA formation during angiotensin II (Ang II) infusion in apolipoprotein E–deficient mice. Methods and Results Six-month-old male apolipoprotein E–deficient mice were infused with Ang II at 1000 ng/kg per minute for 4 weeks via osmotic minipumps while consuming either a regular diet or a diet enriched with vitamin E (2 IU/g of diet). After 4 weeks, abdominal aortic weight and maximal diameter were determined, and aortic tissues were sectioned and examined using biochemical and histological techniques. Vitamin E attenuated formation of AAA, decreasing maximal aortic diameter by 24% and abdominal aortic weight by 34% (P<0.05, respectively). Importantly, animals treated with vitamin E showed a 44% reduction in the combined end point of fatal+nonfatal aortic rupture (P<0.05). Vitamin E also decreased aortic 8-isoprostane content (a marker of oxidative stress) and reduced both aortic macrophage infiltration and osteopontin expression (P<0.05, respectively). Vitamin E treatment had no significant effect on the extent of aortic root atherosclerosis, activation of matrix metalloproteinases 2 or 9, serum lipid profile, or systolic blood pressure. Conclusions Vitamin E ameliorates AAAs and reduces the combined end point of fatal+nonfatal aortic rupture in this animal model. These findings are consistent with the concept that oxidative stress plays a pivotal role in Ang II–driven AAA formation in hyperlipidemic mice. PMID:15933246

Circulating Vascular Basement Membrane Fragments are Associated with the Diameter of the Abdominal Aorta and Their Expression Pattern is Altered in AAA Tissue.

PubMed

Holsti, Mari; Wanhainen, Anders; Lundin, Christina; Björck, Martin; Tegler, Gustaf; Svensson, Johan; Sund, Malin

2018-04-12

Abdominal aortic aneurysm (AAA) is characterised by enhanced proteolytic activity, and extracellular matrix (ECM) remodelling in the vascular wall. Type IV and XVIII collagen/endostatin are structural proteins in vascular basement membrane (VBM), a specialised ECM structure. Here the association between plasma levels of these collagens with the aortic diameter and expansion rate is studied, and their expression in aortic tissue characterised. This was a retrospective population based cohort study. Type IV and XVIII collagen/endostatin were analysed in plasma by ELISA assay in 615 men, divided into three groups based on the aortic diameter: 1) normal aorta ≤ 25 mm, 2) sub-aneurysmal aorta (SAA) 26-29 mm, and 3) AAA ≥ 30 mm. Follow up data were available for 159 men. The association between collagen levels and aortic diameter at baseline, and with the expansion rate at follow up were analysed in ordinal logistic regression and linear regression models, controlling for common confounding factors. Tissue expression of the collagens was analysed in normal aorta (n = 6) and AAA (n = 6) by immunofluorescence. Plasma levels of type XVIII collagen/endostatin (136 ng/mL [SD 29] in individuals with a normal aorta diameter, 154 ng/ml [SD 45] in SAA, and 162 ng/ml [SD 46] in AAA; p = .001) and type IV collagen (105 ng/mL [SD 42] normal aorta, 124 ng/ml [SD 46] SAA, and 127 ng/ml [SD 47] AAA; p = .037) were associated with a larger aortic diameter. A significant association was found between the baseline levels of type XVIII/endostatin and the aortic expansion rate (p = .035), but in the multivariable model, only the initial aortic diameter remained significantly associated with expansion (p = .005). Altered expression patterns of both collagens were observed in AAA tissue. Plasma levels of circulating type IV and XVIII collagen/endostatin increase with AAA diameter. The expression pattern of VBM proteins is altered in the aneurysm wall. Copyright © 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.

Functional Diversity of AAA+ Protease Complexes in Bacillus subtilis

PubMed Central

Elsholz, Alexander K. W.; Birk, Marlene S.; Charpentier, Emmanuelle; Turgay, Kürşad

2017-01-01

Here, we review the diverse roles and functions of AAA+ protease complexes in protein homeostasis, control of stress response and cellular development pathways by regulatory and general proteolysis in the Gram-positive model organism Bacillus subtilis. We discuss in detail the intricate involvement of AAA+ protein complexes in controlling sporulation, the heat shock response and the role of adaptor proteins in these processes. The investigation of these protein complexes and their adaptor proteins has revealed their relevance for Gram-positive pathogens and their potential as targets for new antibiotics. PMID:28748186

Functional Diversity of AAA+ Protease Complexes in Bacillus subtilis.

PubMed

Elsholz, Alexander K W; Birk, Marlene S; Charpentier, Emmanuelle; Turgay, Kürşad

2017-01-01

Here, we review the diverse roles and functions of AAA+ protease complexes in protein homeostasis, control of stress response and cellular development pathways by regulatory and general proteolysis in the Gram-positive model organism Bacillus subtilis . We discuss in detail the intricate involvement of AAA+ protein complexes in controlling sporulation, the heat shock response and the role of adaptor proteins in these processes. The investigation of these protein complexes and their adaptor proteins has revealed their relevance for Gram-positive pathogens and their potential as targets for new antibiotics.

Circulating cadmium concentration and risk of aortic aneurysms: A nested case-control study within the Malmö Diet and Cancer cohort.

PubMed

Fagerberg, Björn; Borné, Yan; Sallsten, Gerd; Smith, J Gustav; Acosta, Stefan; Persson, Margaretha; Melander, Olle; Forsgard, Niklas; Gottsäter, Anders; Hedblad, Bo; Barregard, Lars; Engström, Gunnar

2017-06-01

Diet and smoking expose the general population to cadmium (Cd), which is a toxic metal that accumulates in the arterial wall. In experimental studies, Cd causes reductions in proliferation of smooth muscle cells and cellular synthesis of procollagen. The aim of this study was to examine whether blood Cd levels, a valid measure of Cd exposure, are associated with increased risk of abdominal aortic aneurysm (AAA). All middle-aged men and women enrolled in the Malmö Diet and Cancer study (n = 30 447) were followed from the baseline examination in 1991-1996 through 2009. A total of 297 cases with AAA and two randomly selected control subjects for each case, matched for age and sex, were included. Blood Cd was analysed by inductively coupled plasma mass spectrometry. Diagnoses of AAA, thoracic aortic aneurysm and aortic dissection were obtained from registers. Increased blood Cd was associated with increased risk of incident AAA after adjustment for smoking and other established risk factors for AAA. The highest tertile of blood Cd concentrations had a rate ratio of 2.5 (95% confidence interval 1.3, 5.0) for incident AAA. Concentration of blood Cd (log transformed) was not associated with AAA in never-smokers (n = 24). Blood Cd levels corresponding to the upper tertile of the distribution in the age- and sex-matched control group were associated with a 2.5-fold increase in rate ratio for incident AAA. This relationship was not found in the small group of never-smokers. Copyright © 2017. Published by Elsevier B.V.

Mitochondrial dysfunction: bench-to-bedside optical monitoring of tissue vitality

NASA Astrophysics Data System (ADS)

Mayevsky, Avraham; Dekel, Nava; Oren, Levi; Deutsch, Assaf; Pewzner, Eliyahu

2008-02-01

In normal cell the mitochondria are the major source of energy for cellular functions. They serve as biosensors for oxidative stress and involved also in termination of cell function by apoptosis. The involvement of mitochondria in pathological states such as neurodegenerative diseases, sepsis, stroke and cancer are well documented. The involvement of mitochondrial respiration and function in cancer development, proliferation and possible therapy were initiated 75 years ago by Otto Warburg. Monitoring of NADH fluorescence in vivo as an intracellular oxygen indicator was established in the 1950-1970 by Britton Chance and collaborators. In the last 20 years we developed and used a multiparametric monitoring system enabling real time assessment of mitochondria NADH, microcirculatory blood flow and volume as well as HbO II oxygenation. In order to use this technology in clinical practice the commercial developed device-the "CritiView" was tested in animal models as well as in patients hospitalized in the critical care departments. In patients we tested the viability of the urethral wall (a less-vital tissue) by a 3 way Foley urinary catheter that contains the optical probe. The catheter was introduced to patients underwent open heart by-pass surgery or abdominal aorta aneurysm (AAA) operations. The monitoring started immediately after the insertion of the catheter to the patient and was stopped when the patient was discharged from the operation room. The results show that monitoring of the vitality of the Urethral wall provides information in correlation to the surgical procedure performed. In the AAA patients the occlusion of the aorta led to severe ischemia developed in the urethral wall and recovery of signals were recorded after the reopening of the aorta. In patients under went heart bypass surgery the urethra vitality was decreased dramatically during the operation and recovery was noted in most patients after the discharge of the patient from the operation room.

Combination Therapy with Atorvastatin and Amlodipine Suppresses Angiotensin II-Induced Aortic Aneurysm Formation

PubMed Central

Takahashi, Kikuyo; Matsumoto, Yasuharu; Do.e, Zhulanqiqige; Kanazawa, Masanori; Satoh, Kimio; Shimizu, Takuya; Sato, Akira; Fukumoto, Yoshihiro; Shimokawa, Hiroaki

2013-01-01

Background Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease. It is controversial whether statin and calcium channel blockers (CCBs) has an inhibitory effect on the expansion of AAA. Some studies reported that CCBs have an inhibitory effect on Rho-kinase activity. Rho-kinase plays an important role in the pathogenesis of various cardiovascular diseases. However, there is no study reporting of the association between Rho-kinase and human AAAs. Methods and Results Experimental AAA was induced in Apolipoprotein E-deficient (ApoE-/-) mice infused with angiotensin II (AngII) for 28 days. They were randomly divided into the following 5 groups; saline infusion alone (sham), AngII infusion alone, AngII infusion plus atorvastatin (10 mg/kg/day), AngII infusion plus amlodipine (1 mg/kg/day), and AngII infusion plus combination therapy with atorvastatin (10 mg/kg/day) and amlodipine (1 mg/kg/day). The combination therapy significantly suppressed AngII-induced increase in maximal aortic diameter as compared with sham, whereas each monotherapy had no inhibitory effects. The combination therapy significantly reduced AngII-induced apoptosis and elastin degradation at the AAA lesion, whereas each monotherapy did not. Moreover, Rho-kinase activity, as evaluated by the extent of phosphorylation of myosin-binding subunit (a substrate of Rho-kinase) and matrix metalloproteinase activity were significantly increased in the AngII-induced AAA lesion as compared with sham, both of which were again significantly suppressed by the combination therapy. In human aortic samples, immunohistochemistory revealed that the activity and expression of Rho-kinase was up-regulated in AAA lesion as compared with abdominal aorta from control subjects. Conclusions Rho-kinase is up-regulated in the aortic wall of human AAA. The combination therapy with amlodipine and Atorvastatin, but not each monotherapy, suppresses AngII-induced AAA formation in mice in vivo, for which Rho-kinase inhibition may be involved. PMID:23967318

Mechanics, Mechanobiology, and Modeling of Human Abdominal Aorta and Aneurysms

PubMed Central

Humphrey, J.D.; Holzapfel, G.A.

2011-01-01

Biomechanical factors play fundamental roles in the natural history of abdominal aortic aneurysms (AAAs) and their responses to treatment. Advances during the past two decades have increased our understanding of the mechanics and biology of the human abdominal aorta and AAAs, yet there remains a pressing need for considerable new data and resulting patient-specific computational models that can better describe the current status of a lesion and better predict the evolution of lesion geometry, composition, and material properties and thereby improve interventional planning. In this paper, we briefly review data on the structure and function of the human abdominal aorta and aneurysmal wall, past models of the mechanics, and recent growth and remodeling models. We conclude by identifying open problems that we hope will motivate studies to improve our computational modeling and thus general understanding of AAAs. PMID:22189249

SMYD2 promoter DNA methylation is associated with abdominal aortic aneurysm (AAA) and SMYD2 expression in vascular smooth muscle cells.

PubMed

Toghill, Bradley J; Saratzis, Athanasios; Freeman, Peter J; Sylvius, Nicolas; Bown, Matthew J

2018-01-01

Abdominal aortic aneurysm (AAA) is a deadly cardiovascular disease characterised by the gradual, irreversible dilation of the abdominal aorta. AAA is a complex genetic disease but little is known about the role of epigenetics. Our objective was to determine if global DNA methylation and CpG-specific methylation at known AAA risk loci is associated with AAA, and the functional effects of methylation changes. We assessed global methylation in peripheral blood mononuclear cell DNA from 92 individuals with AAA and 93 controls using enzyme-linked immunosorbent assays, identifying hyper-methylation in those with large AAA and a positive linear association with AAA diameter ( P  < 0.0001, R 2  = 0.3175).We then determined CpG methylation status of regulatory regions in genes located at AAA risk loci identified in genome-wide association studies, using bisulphite next-generation sequencing (NGS) in vascular smooth muscle cells (VSMCs) taken from aortic tissues of 44 individuals (24 AAAs and 20 controls). In IL6R , 2 CpGs were hyper-methylated ( P  = 0.0145); in ERG , 13 CpGs were hyper-methylated ( P  = 0.0005); in SERPINB9 , 6 CpGs were hypo-methylated ( P  = 0.0037) and 1 CpG was hyper-methylated ( P  = 0.0098); and in SMYD2 , 4 CpGs were hypo-methylated ( P  = 0.0012).RT-qPCR was performed for each differentially methylated gene on mRNA from the same VSMCs and compared with methylation. This analysis revealed downregulation of SMYD2 and SERPINB9 in AAA, and a direct linear relationship between SMYD2 promoter methylation and SMYD2 expression ( P  = 0.038). Furthermore, downregulation of SMYD2 at the site of aneurysm in the aortic wall was further corroborated in 6 of the same samples used for methylation and gene expression analysis with immunohistochemistry. This study is the first to assess DNA methylation in VSMCs from individuals with AAA using NGS, and provides further evidence there is an epigenetic basis to AAA. Our study shows that methylation status of the SMYD2 promoter may be linked with decreased SMYD2 expression in disease pathobiology. In support of our work, downregulated SMYD2 has previously been associated with adverse cardiovascular physiology and inflammation, which are both hallmarks of AAA. The identification of such adverse epigenetic modifications could potentially contribute towards the development of epigenetic treatment strategies in the future.

m-AAA and i-AAA complexes coordinate to regulate OMA1, the stress-activated supervisor of mitochondrial dynamics.

PubMed

Consolato, Francesco; Maltecca, Francesca; Tulli, Susanna; Sambri, Irene; Casari, Giorgio

2018-04-09

The proteolytic processing of dynamin-like GTPase OPA1, mediated by the activity of both YME1L1 [intermembrane (i)-AAA protease complex] and OMA1, is a crucial step in the regulation of mitochondrial dynamics. OMA1 is a zinc metallopeptidase of the inner mitochondrial membrane that undergoes pre-activating proteolytic and auto-proteolytic cleavage after mitochondrial import. Here, we identify AFG3L2 [matrix (m) - AAA complex] as the major protease mediating this event, which acts by maturing the 60 kDa pre-pro-OMA1 to the 40 kDa pro-OMA1 form by severing the N-terminal portion without recognizing a specific consensus sequence. Therefore, m - AAA and i - AAA complexes coordinately regulate OMA1 processing and turnover, and consequently control which OPA1 isoforms are present, thus adding new information on the molecular mechanisms of mitochondrial dynamics and neurodegenerative diseases affected by these phenomena.This article has an associated First Person interview with the first author of the paper. © 2018. Published by The Company of Biologists Ltd.

Inflammatory cell phenotypes in AAAs: their role and potential as targets for therapy.

PubMed

Dale, Matthew A; Ruhlman, Melissa K; Baxter, B Timothy

2015-08-01

Abdominal aortic aneurysms (AAAs) are characterized by chronic inflammatory cell infiltration. AAA is typically an asymptomatic disease and caused ≈15 000 deaths annually in the United States. Previous studies have examined both human and murine aortic tissue for the presence of various inflammatory cell types. Studies show that in both human and experimental AAAs, prominent inflammatory cell infiltration, such as CD4(+) T cells and macrophages, occurs in the damaged aortic wall. These cells have the ability to undergo phenotypic modulation based on microenvironmental cues, potentially influencing disease progression. Proinflammatory CD4(+) T cells and classically activated macrophages dominate the landscape of aortic infiltrates. The skew to proinflammatory phenotypes alters disease progression and plays a role in causing chronic inflammation. The local cytokine production and presence of inflammatory mediators, such as extracellular matrix breakdown products, influence the uneven balance of the inflammatory infiltrate phenotypes. Understanding and developing new strategies that target the proinflammatory phenotype could provide useful therapeutic targets for a disease with no current pharmacological intervention. © 2015 American Heart Association, Inc.

A mathematical model of aortic aneurysm formation

PubMed Central

Hao, Wenrui; Gong, Shihua; Wu, Shuonan; Xu, Jinchao; Go, Michael R.; Friedman, Avner; Zhu, Dai

2017-01-01

Abdominal aortic aneurysm (AAA) is a localized enlargement of the abdominal aorta, such that the diameter exceeds 3 cm. The natural history of AAA is progressive growth leading to rupture, an event that carries up to 90% risk of mortality. Hence there is a need to predict the growth of the diameter of the aorta based on the diameter of a patient’s aneurysm at initial screening and aided by non-invasive biomarkers. IL-6 is overexpressed in AAA and was suggested as a prognostic marker for the risk in AAA. The present paper develops a mathematical model which relates the growth of the abdominal aorta to the serum concentration of IL-6. Given the initial diameter of the aorta and the serum concentration of IL-6, the model predicts the growth of the diameter at subsequent times. Such a prediction can provide guidance to how closely the patient’s abdominal aorta should be monitored. The mathematical model is represented by a system of partial differential equations taking place in the aortic wall, where the media is assumed to have the constituency of an hyperelastic material. PMID:28212412

Genetic variation within the Y chromosome is not associated with histological characteristics of the atherosclerotic carotid artery or aneurysmal wall.

PubMed

Haitjema, Saskia; van Setten, Jessica; Eales, James; van der Laan, Sander W; Gandin, Ilaria; de Vries, Jean-Paul P M; de Borst, Gert J; Pasterkamp, Gerard; Asselbergs, Folkert W; Charchar, Fadi J; Wilson, James F; de Jager, Saskia C A; Tomaszewski, Maciej; den Ruijter, Hester M

2017-04-01

Haplogroup I, a common European paternal lineage of the Y chromosome, is associated with increased risk of coronary artery disease in British men. It is unclear whether this haplogroup or any other haplogroup on the Y chromosome is associated with histological characteristics of the diseased vessel wall in other vascular manifestations of cardiovascular diseases showing a male preponderance. We examined Dutch men undergoing either carotid endarterectomy from the Athero-Express biobank (AE, n = 1217) or open aneurysm repair from the Aneurysm-Express biobank (AAA, n = 393). Upon resolving the Y chromosome phylogeny, each man was assigned to one of the paternal lineages based on combinations of single nucleotide polymorphisms of the male-specific region of the Y chromosome. We examined the associations between the Y chromosome and the histological characteristics of the carotid plaque and aneurysm wall, including lipid content, leukocyte infiltration and intraplaque haemorrhage, in all men. A majority of men were carriers of either haplogroup I (AE: 28% AAA: 24%) or haplogroup R (AE: 59% AAA: 61%). We found no association between Y chromosomal haplogroups and histological characteristics of plaque collected from carotid arteries or tissue specimens of aneurysms. Moreover, the distribution of frequency for all Y chromosomal haplogroups in both cohorts was similar to that of a general population of Dutch men. Our data show that genetic variation on the Y chromosome is not associated with histological characteristics of the plaques from carotid arteries or specimens of aneurysms in men of Dutch origin. Copyright © 2017 Elsevier B.V. All rights reserved.

Endothelial and smooth muscle cells from abdominal aortic aneurysm have increased oxidative stress and telomere attrition.

PubMed

Cafueri, Giuseppe; Parodi, Federica; Pistorio, Angela; Bertolotto, Maria; Ventura, Francesco; Gambini, Claudio; Bianco, Paolo; Dallegri, Franco; Pistoia, Vito; Pezzolo, Annalisa; Palombo, Domenico

2012-01-01

Abdominal aortic aneurysm (AAA) is a complex multi-factorial disease with life-threatening complications. AAA is typically asymptomatic and its rupture is associated with high mortality rate. Both environmental and genetic risk factors are involved in AAA pathogenesis. Aim of this study was to investigate telomere length (TL) and oxidative DNA damage in paired blood lymphocytes, aortic endothelial cells (EC), vascular smooth muscle cells (VSMC), and epidermal cells from patients with AAA in comparison with matched controls. TL was assessed using a modification of quantitative (Q)-FISH in combination with immunofluorescence for CD31 or α-smooth muscle actin to detect EC and VSMC, respectively. Oxidative DNA damage was investigated by immunofluorescence staining for 7, 8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dG). Telomeres were found to be significantly shortened in EC, VSMC, keratinocytes and blood lymphocytes from AAA patients compared to matched controls. 8-oxo-dG immunoreactivity, indicative of oxidative DNA damage, was detected at higher levels in all of the above cell types from AAA patients compared to matched controls. Increased DNA double strand breaks were detected in AAA patients vs controls by nuclear staining for γ-H2AX histone. There was statistically significant inverse correlation between TL and accumulation of oxidative DNA damage in blood lymphocytes from AAA patients. This study shows for the first time that EC and VSMC from AAA have shortened telomeres and oxidative DNA damage. Similar findings were obtained with circulating lymphocytes and keratinocytes, indicating the systemic nature of the disease. Potential translational implications of these findings are discussed.

PET Imaging of Abdominal Aortic Aneurysm with 64Cu-Labeled Anti-CD105 Antibody Fab Fragment.

PubMed

Shi, Sixiang; Orbay, Hakan; Yang, Yunan; Graves, Stephen A; Nayak, Tapas R; Hong, Hao; Hernandez, Reinier; Luo, Haiming; Goel, Shreya; Theuer, Charles P; Nickles, Robert J; Cai, Weibo

2015-06-01

The critical challenge in abdominal aortic aneurysm (AAA) research is the accurate diagnosis and assessment of AAA progression. Angiogenesis is a pathologic hallmark of AAA, and CD105 is highly expressed on newly formed vessels. Our goal was to use (64)Cu-labeled anti-CD105 antibody Fab fragment for noninvasive assessment of angiogenesis in the aortic wall in a murine model of AAA. Fab fragment of TRC105, a mAb that specifically binds to CD105, was generated by enzymatic papain digestion and conjugated to NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid) for (64)Cu labeling. The binding affinity/specificity of NOTA-TRC105-Fab was evaluated by flow cytometry and various ex vivo studies. BALB/c mice were anesthetized and treated with calcium phosphate to induce AAA and underwent weekly PET scans using (64)Cu-NOTA-TRC105-Fab. Biodistribution and autoradiography studies were also performed to confirm the accuracy of PET results. NOTA-TRC105-Fab exhibited high purity and specifically bound to CD105 in vitro. Uptake of (64)Cu-NOTA-TRC105-Fab increased from a control level of 3.4 ± 0.1 to 9.5 ± 0.4 percentage injected dose per gram (%ID/g) at 6 h after injection on day 5 and decreased to 7.2 ± 1.4 %ID/g on day 12, which correlated well with biodistribution and autoradiography studies (i.e., much higher tracer uptake in AAA than normal aorta). Of note, enhanced AAA contrast was achieved, due to the minimal background in the abdominal area of mice. Degradation of elastic fibers and highly expressed CD105 were observed in ex vivo studies. (64)Cu-NOTA-TRC105-Fab cleared rapidly through the kidneys, which enabled noninvasive PET imaging of the aorta with enhanced contrast and showed increased angiogenesis (CD105 expression) during AAA. (64)Cu-NOTA-TRC105-Fab PET may potentially be used for future diagnosis and prognosis of AAA. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Adventitial Tertiary Lymphoid Organs as Potential Source of MicroRNA Biomarkers for Abdominal Aortic Aneurysm

PubMed Central

Spear, Rafaelle; Boytard, Ludovic; Blervaque, Renaud; Chwastyniak, Maggy; Hot, David; Vanhoutte, Jonathan; Staels, Bart; Lemoine, Yves; Lamblin, Nicolas; Pruvot, François-René; Haulon, Stephan; Amouyel, Philippe; Pinet, Florence

2015-01-01

Abdominal aortic aneurysm (AAA) is an inflammatory disease associated with marked changes in the cellular composition of the aortic wall. This study aims to identify microRNA (miRNA) expression in aneurysmal inflammatory cells isolated by laser microdissection from human tissue samples. The distribution of inflammatory cells (neutrophils, B and T lymphocytes, mast cells) was evaluated in human AAA biopsies. We observed in half of the samples that adventitial tertiary lymphoid organs (ATLOs) with a thickness from 0.5 to 2 mm were located exclusively in the adventitia. Out of the 850 miRNA that were screened by microarray in isolated ATLOs (n = 2), 164 miRNAs were detected in ATLOs. The three miRNAs (miR-15a-3p, miR-30a-5p and miR-489-3p) with the highest expression levels were chosen and their expression quantified by RT-PCR in isolated ATLOs (n = 4), M1 (n = 2) and M2 macrophages (n = 2) and entire aneurysmal biopsies (n = 3). Except for the miR-30a-5p, a similar modulation was found in ATLOs and the two subtypes of macrophages. The modulated miRNAs were then evaluated in the plasma of AAA patients for their potential as AAA biomarkers. Our data emphasize the potential of miR-15a-3p and miR-30a-5p as biomarkers of AAA but also as triggers of ATLO evolution. Further investigations will be required to evaluate their targets in order to better understand AAA pathophysiology. PMID:25993295

Inhibition of early AAA formation by aortic intraluminal pentagalloyl glucose (PGG) infusion in a novel porcine AAA model.

PubMed

Kloster, Brian O; Lund, Lars; Lindholt, Jes S

2016-05-01

The vast majority of abdominal aortic aneurysms found in screening programs are small, and as no effective treatment exits, many will expand until surgery is indicated. Therefore, it remains intriguing to develop a safe and low cost treatment of these small aneurysms, that is able to prevent or delay their expansion. In this study, we investigated whether intraluminal delivered pentagalloyl glucose (PGG) can impair the early AAA development in a porcine model. The infrarenal aorta was exposed in thirty pigs. Twenty underwent an elastase based AAA inducing procedure and ten of these received an additional intraluminal PGG infusion. The final 10 were sham operated and served as controls. All pigs who only had an elastase infusion developed macroscopically expanding AAAs. In pigs treated with an additional PGG infusion the growth rate of the AP-diameter rapidly returned to physiological values as seen in the control group. In the elastase group, histology revealed more or less complete resolution of the elastic lamellae in the media while they were more abundant, coherent and structurally organized in the PGG group. The control group displayed normal physiological growth and histology. In our model, intraluminal delivered PGG is able to penetrate the aortic wall from the inside and impair the early AAA development by stabilizing the elastic lamellae and preserving their integrity. The principle holds a high clinical potential if it can be translated to human conditions, since it, if so, potentially could represent a new drug for stabilizing small abdominal aneurysms.

Label-free quantitative proteomic analysis of human plasma-derived microvesicles to find protein signatures of abdominal aortic aneurysms.

PubMed

Martinez-Pinna, Roxana; Gonzalez de Peredo, Anne; Monsarrat, Bernard; Burlet-Schiltz, Odile; Martin-Ventura, Jose Luis

2014-08-01

To find potential biomarkers of abdominal aortic aneurysms (AAA), we performed a differential proteomic study based on human plasma-derived microvesicles. Exosomes and microparticles isolated from plasma of AAA patients and control subjects (n = 10 each group) were analyzed by a label-free quantitative MS-based strategy. Homemade and publicly available software packages have been used for MS data analysis. The application of two kinds of bioinformatic tools allowed us to find differential protein profiles from AAA patients. Some of these proteins found by the two analysis methods belong to main pathological mechanisms of AAA such as oxidative stress, immune-inflammation, and thrombosis. Data analysis from label-free MS-based experiments requires the use of sophisticated bioinformatic approaches to perform quantitative studies from complex protein mixtures. The application of two of these bioinformatic tools provided us a preliminary list of differential proteins found in plasma-derived microvesicles not previously associated to AAA, which could help us to understand the pathological mechanisms related to this disease. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Total laparorobotic repair of abdominal aortic aneurysm with sac exclusion obliteration and aortobifemoral bypass.

PubMed

Wu, Timothy; Prema, Jateen; Zagaja, Gregory; Shalhav, Arieh; Bassiouny, Hisham S

2009-01-01

A 65-year-old man with coronary artery disease, hypertension, and peripheral vascular disease was found to have an asymptomatic abdominal aortic aneurysm (AAA) of 5.5 cm on surveillance for his peripheral vascular disease. Cardiac stress testing demonstrated no evidence of myocardial ischemia, and he opted to undergo open repair of his aneurysm. Laparorobotic repair of the infrarenal AAA using the da Vinci robotic system was performed with an aortobifemoral bypass. We describe a novel technique for AAA exclusion using a cerclage method, which greatly facilitates repair of infrarenal AAAs using laparorobotic techniques. Laparorobotic repair of infrarenal AAA can be greatly facilitated by AAA sac exclusion and obliteration without the need to ligate all lumbar arteries or to open the aneurysm. This virtually avoids blood loss from the sac and minimizes the possibility for open conversion as a result of poor visualization. Minimally invasive aortic intervention for aneurysmal disease using laparascopic methods has been reported in the literature. Problems associated with this technique include a prolonged learning curve and difficulty completing intracorporeal anastomoses. Robotic surgery provides an advantage over laparoscopic surgery in its ability to provide greater degrees of freedom in a relatively small field of view along with superior high-definition, three-dimensional visualization. To date, there have been no known reports of using robotic surgery in the United States as a sole method for repair of AAA. We report our technique of combining robotic surgery with a novel procedure for sac exclusion and obliteration to successfully repair AAA without the need for opening the aneurysm sac and endoaneurysmorrhaphy.

Determining the influence of calcification on the failure properties of abdominal aortic aneurysm (AAA) tissue.

PubMed

O'Leary, Siobhan A; Mulvihill, John J; Barrett, Hilary E; Kavanagh, Eamon G; Walsh, Michael T; McGloughlin, Tim M; Doyle, Barry J

2015-02-01

Varying degrees of calcification are present in most abdominal aortic aneurysms (AAAs). However, their impact on AAA failure properties and AAA rupture risk is unclear. The aim of this work is evaluate and compare the failure properties of partially calcified and predominantly fibrous AAA tissue and investigate the potential reasons for failure. Uniaxial mechanical testing was performed on AAA samples harvested from 31 patients undergoing open surgical repair. Individual tensile samples were divided into two groups: fibrous (n=31) and partially calcified (n=38). The presence of calcification was confirmed by fourier transform infrared spectroscopy (FTIR). A total of 69 mechanical tests were performed and the failure stretch (λf), failure stress (σf) and failure tension (Tf) were recorded for each test. Following mechanical testing, the failure sites of a subset of both tissue types were examined using scanning electron microscopy (SEM)/energy dispersive X-ray spectroscopy (EDS) to investigate the potential reasons for failure. It has been shown that the failure properties of partially calcified tissue are significantly reduced compared to fibrous tissue and SEM and EDS results suggest that the junction between a calcification deposit and the fibrous matrix is highly susceptible to failure. This study implicates the presence of calcification as a key player in AAA rupture risk and provides further motivation for the development of non-invasive methods of measuring calcification. Copyright © 2014 Elsevier Ltd. All rights reserved.

Systemic Upregulation of IL-10 (Interleukin-10) Using a Nonimmunogenic Vector Reduces Growth and Rate of Dissecting Abdominal Aortic Aneurysm.

PubMed

Adam, Matti; Kooreman, Nigel; Jagger, Ann; Wagenhaeuser, Markus U; Mehrkens, Dennis; Wang, Yongming; Kayama, Yosuke; Toyama, Kensuke; Raaz, Uwe; Schellinger, Isabel N; Maegdefessel, Lars; Spin, Joshua M; Hamming, Jaap F; Quax, Paul H A; Baldus, Stephan; Wu, Joseph C; Tsao, Philip S

2018-06-07

Recruitment of immunologic competent cells to the vessel wall is a crucial step in formation of abdominal aortic aneurysms (AAA). Innate immunity effectors (eg, macrophages), as well as mediators of adaptive immunity (eg, T cells), orchestrate a local vascular inflammatory response. IL-10 (interleukin-10) is an immune-regulatory cytokine with a crucial role in suppression of inflammatory processes. We hypothesized that an increase in systemic IL-10-levels would mitigate AAA progression. Using a single intravenous injection protocol, we transfected an IL-10 transcribing nonimmunogenic minicircle vector into the Ang II (angiotensin II)-ApoE -/- infusion mouse model of AAA. IL-10 minicircle transfection significantly reduced average aortic diameter measured via ultrasound at day 28 from 166.1±10.8% (control) to 131.0±5.8% (IL-10 transfected). Rates of dissecting AAA were reduced by IL-10 treatment, with an increase in freedom from dissecting AAA from 21.5% to 62.3%. Using flow cytometry of aortic tissue from minicircle IL-10-treated animals, we found a significantly higher percentage of CD4 + /CD25 + /Foxp3 (forkhead box P3) + regulatory T cells, with fewer CD8 + /Granzyme B + cytotoxic T cells. Furthermore, isolated aortic macrophages produced less TNF-α (tumor necrosis factor-α), more IL-10, and were more likely to be MRC1 (mannose receptor, C type 1)-positive alternatively activated macrophages. These results concurred with gene expression analysis of LPS-stimulated and Ang II-primed human peripheral blood mononuclear cells. Taken together, we provide an effective gene therapy approach to AAA in mice by enhancing antiinflammatory and dampening proinflammatory pathways through minicircle-induced augmentation of systemic IL-10 expression. © 2018 American Heart Association, Inc.

Rationale and Design of the ARREST Trial Investigating Mesenchymal Stem Cells in the Treatment of Small Abdominal Aortic Aneurysm.

PubMed

Wang, S Keisin; Green, Linden A; Gutwein, Ashley R; Drucker, Natalie A; Motaganahalli, Raghu L; Fajardo, Andres; Babbey, Clifford M; Murphy, Michael P

2018-02-01

Abdominal aortic aneurysms (AAAs) are a major source of morbidity and mortality despite continuing advances in surgical technique and care. Although the inciting factors for AAA development continue to be elusive, accumulating evidence suggests a significant periaortic inflammatory response leading to degradation and dilation of the aortic wall. Previous human trials have demonstrated safety and efficacy of mesenchymal stem cells (MSCs) in the treatment of inflammation-related pathologies such as rheumatoid arthritis, graft versus host disease, and transplant rejection. Therefore, herein, we describe the Aortic Aneurysm Repression with Mesenchymal Stem Cells (ARREST) trial, a phase I investigation into the safety of MSC infusion for patients with small AAA and the cells' effects on modulation of AAA-related inflammation. ARREST is a phase I, single-center, double-blind, randomized controlled trial (RCT) investigating infusion both dilute and concentrated MSCs compared to placebo in 36 small AAA (35-45 mm) patients. Subjects will be followed by study personnel for 12 months to ascertain incidence of adverse events, immune cell phenotype expression, peripheral cytokine profile, and periaortic inflammation. Maximum transverse aortic diameter will be assessed regularly for 5 years by a combination of computed tomography and duplex sonography. Four patients have thus far been enrolled, randomized, and treated per protocol. We anticipate the conclusion of the treatment phase within the next 24 months with ongoing long-term follow-up. ARREST will be pivotal in assessing the safety of MSC infusion and provide preliminary data on the ability of MSCs to favorably modulate the pathogenic AAA host immune response. The data gleaned from this phase I trial will provide the groundwork for a larger, phase III RCT which may provide the first pharmaceutical intervention for AAA. Copyright © 2017 Elsevier Inc. All rights reserved.

Endothelial MMP-9 drives the inflammatory response in abdominal aortic aneurysm (AAA).

PubMed

Ramella, Martina; Boccafoschi, Francesca; Bellofatto, Kevin; Md, Antonia Follenzi; Fusaro, Luca; Boldorini, Renzo; Casella, Francesco; Porta, Carla; Settembrini, Piergiorgio; Cannas, Mario

2017-01-01

Progression of abdominal aortic aneurysm (AAA) is typified by chronic inflammation and extracellular matrix (ECM) degradation of the aortic wall. Vascular inflammation involves complex interactions among inflammatory cells, endothelial cells (ECs), vascular smooth muscle cells (vSMCs), and ECM. Although vascular endothelium and medial neoangiogenesis play a key role in AAA, the molecular mechanisms underlying their involvement are only partially understood. In AAA biopsies, we found increased MMP-9, IL-6, and monocyte chemoattractant protein-1 (MCP-1), which correlated with massive medial neo-angiogenesis (C4d positive staining). In this study, we developed an in vitro model in order to characterize the role of endothelial matrix metalloproteinase-9 (e-MMP-9) as a potential trigger of medial disruption and in the inflammatory response bridging between ECs and vSMC. Lentiviral-mediated silencing of e-MMP-9 through RNA interference inhibited TNF-alpha-mediated activation of NF-κB in EA.hy926 human endothelial cells. In addition, EA.hy926 cells void of MMP-9 failed to migrate in a 3D matrix. Moreover, silenced EA.hy926 affected vSMC behavior in terms of matrix remodeling. In fact, also MMP-9 in vSMC resulted inhibited when endothelial MMP-9 was suppressed.

Regulatory coiled-coil domains promote head-to-head assemblies of AAA+ chaperones essential for tunable activity control.

PubMed

Carroni, Marta; Franke, Kamila B; Maurer, Michael; Jäger, Jasmin; Hantke, Ingo; Gloge, Felix; Linder, Daniela; Gremer, Sebastian; Turgay, Kürşad; Bukau, Bernd; Mogk, Axel

2017-11-22

Ring-forming AAA+ chaperones exert ATP-fueled substrate unfolding by threading through a central pore. This activity is potentially harmful requiring mechanisms for tight repression and substrate-specific activation. The AAA+ chaperone ClpC with the peptidase ClpP forms a bacterial protease essential to virulence and stress resistance. The adaptor MecA activates ClpC by targeting substrates and stimulating ClpC ATPase activity. We show how ClpC is repressed in its ground state by determining ClpC cryo-EM structures with and without MecA. ClpC forms large two-helical assemblies that associate via head-to-head contacts between coiled-coil middle domains (MDs). MecA converts this resting state to an active planar ring structure by binding to MD interaction sites. Loss of ClpC repression in MD mutants causes constitutive activation and severe cellular toxicity. These findings unravel an unexpected regulatory concept executed by coiled-coil MDs to tightly control AAA+ chaperone activity.

Prophylactic Mesh Reinforcement versus Sutured Closure to Prevent Incisional Hernias after Open Abdominal Aortic Aneurysm Repair via Midline Laparotomy: A Systematic Review and Meta-Analysis.

PubMed

Indrakusuma, Reza; Jalalzadeh, Hamid; van der Meij, Jessica E; Balm, Ron; Koelemay, Mark J W

2018-04-20

Incisional hernia is a frequent late complication after open abdominal aortic aneurysm (AAA) repair. We aimed to determine whether prophylactic mesh reinforcement of the abdominal wall at open AAA repair via midline laparotomy reduces the rate of incisional hernia compared to standard sutured closure. A systematic review and meta-analysis was carried out in accordance with the PRISMA statement (PROSPERO registration CRD42017072508). Randomised controlled trials (RCTs) comparing prophylactic mesh reinforcement with standard sutured closure were eligible for inclusion. MEDLINE, Embase, and the Cochrane Library were searched. A meta-analysis with a random effects model was carried out to estimate pooled risk ratios (RR) with 95% confidence intervals (CIs) for the incidence of, and re-operation rate for, incisional hernias. Assessments of methodological quality, quality of evidence, and strength of recommendations were done with the Cochrane Collaboration's tool for assessing risk of bias and the GRADE approach. Four RCTs with a total of 388 patients were included in the meta-analysis. Pooled analysis showed that mesh reinforcement significantly reduced the risk of incisional hernia after AAA repair compared with standard sutured closure (RR 0.27, 95% CI 0.11-0.66). The pooled rate of re-operations was not different between groups (RR 0.23, 95% CI 0.11-1.05). Mesh reinforcement did not cause more intra-operative or post-operative complications than sutured closure. The risk of bias in studies was low and the quality of evidence was rated as moderate. Prophylactic mesh reinforcement of the abdominal wall after open AAA repair via midline laparotomy significantly reduces the risk of incisional hernia. However, no significant difference in re-operation for incisional hernia was found. Copyright © 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.

Analysis of reactive oxygen metabolites (ROMs) after cardiovascular surgery as a marker of oxidative stress.

PubMed

Kanaoka, Yuji; Inagaki, Ei-ichirou; Hamanaka, Souhei; Masaki, Hisao; Tanemoto, Kazuo

2010-10-01

The transient systemic low perfusion that occurs during cardiovascular surgery leads to oxidative stress and the production of free radicals. A systemic increase of various markers of oxidative stress has been shown to occur during cardiopulmonary bypass (CPB). However, these markers have not been adequately evaluated because they seem to be reactive and short-lived. Here, oxidative stress was measured using the free radical analytical system (FRAS 4) assessing the derivatives of reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP). Blood samples were taken from 21 patients undergoing elective cardiovascular surgery. CPB was used in 15 patients, and abdominal aortic aneurysm (AAA) surgery without CPB was performed in 6. Measurements of d-ROMs and BAP were taken before surgery, 1 day, 1 week, and 2 weeks after surgery, and oxidative stress was evaluated. The d-ROM level increased gradually after cardiovascular surgery up to 2 weeks. Over time, the d-ROM level after surgery involving CPB became higher than that after AAA surgery. This difference reached statistical significance at 1 week and lasted to 2 weeks. The prolongation of CPB was prone to elevate the d-ROM level whereas the duration of the aortic clamp in AAA surgery had no relation to the d-ROM level. The BAP was also elevated after surgery, and was positively correlated with the level of d-ROMs. In this study, patients who underwent cardiovascular surgery involving CPB had significant oxidative damage. The production of ROMs was shown to depend on the duration of CPB. Damage can be reduced if CPB is avoided. When CPB must be used, shortening the CPB time may be effective in reducing oxidative stress.

Integrated regulation of PIKK-mediated stress responses by AAA+ proteins RUVBL1 and RUVBL2

PubMed Central

Izumi, Natsuko; Yamashita, Akio; Ohno, Shigeo

2012-01-01

Proteins of the phosphatidylinositol 3-kinase-related protein kinase (PIKK) family are activated by various cellular stresses, including DNA damage, premature termination codon and nutritional status, and induce appropriate cellular responses. The importance of PIKK functions in the maintenance of genome integrity, accurate gene expression and the proper control of cell growth/proliferation is established. Recently, ATPase associated diverse cellular activities (AAA+) proteins RUVBL1 and RUVBL2 (RUVBL1/2) have been shown to be common regulators of PIKKs. The RUVBL1/2 complex regulates PIKK-mediated stress responses through physical interactions with PIKKs and by controlling PIKK mRNA levels. In this review, the functions of PIKKs in stress responses are outlined and the physiological significance of the integrated regulation of PIKKs by the RUVBL1/2 complex is presented. We also discuss a putative “PIKK regulatory chaperone complex” including other PIKK regulators, Hsp90 and the Tel2 complex. PMID:22540023

PspF-binding domain PspA1-144 and the PspA·F complex: New insights into the coiled-coil-dependent regulation of AAA+ proteins.

PubMed

Osadnik, Hendrik; Schöpfel, Michael; Heidrich, Eyleen; Mehner, Denise; Lilie, Hauke; Parthier, Christoph; Risselada, H Jelger; Grubmüller, Helmut; Stubbs, Milton T; Brüser, Thomas

2015-11-01

Phage shock protein A (PspA) belongs to the highy conserved PspA/IM30 family and is a key component of the stress inducible Psp system in Escherichia coli. One of its central roles is the regulatory interaction with the transcriptional activator of this system, the σ(54) enhancer-binding protein PspF, a member of the AAA+ protein family. The PspA/F regulatory system has been intensively studied and serves as a paradigm for AAA+ enzyme regulation by trans-acting factors. However, the molecular mechanism of how exactly PspA controls the activity of PspF and hence σ(54) -dependent expression of the psp genes is still unclear. To approach this question, we identified the minimal PspF-interacting domain of PspA, solved its structure, determined its affinity to PspF and the dissociation kinetics, identified residues that are potentially important for PspF regulation and analyzed effects of their mutation on PspF in vivo and in vitro. Our data indicate that several characteristics of AAA+ regulation in the PspA·F complex resemble those of the AAA+ unfoldase ClpB, with both proteins being regulated by a structurally highly conserved coiled-coil domain. The convergent evolution of both regulatory domains points to a general mechanism to control AAA+ activity for divergent physiologic tasks via coiled-coil domains. © 2015 John Wiley & Sons Ltd.

Inflammatory cell phenotypes in AAAs; their role and potential as targets for therapy

PubMed Central

Dale, Matthew A; Ruhlman, Melissa K.; Baxter, B. Timothy

2015-01-01

Abdominal aortic aneurysms are characterized by chronic inflammatory cell infiltration. AAA is typically an asymptomatic disease and caused approximately 15,000 deaths annually in the U.S. Previous studies have examined both human and murine aortic tissue for the presence of various inflammatory cell types. Studies show that in both human and experimental AAAs, prominent inflammatory cell infiltration, such as CD4+ T cells and macrophages, occurs in the damaged aortic wall. These cells have the ability to undergo phenotypic modulation based on microenvironmental cues, potentially influencing disease progression. Pro-inflammatory CD4+ T cells and classically activated macrophages dominate the landscape of aortic infiltrates. The skew to pro-inflammatory phenotypes alters disease progression and plays a role in causing chronic inflammation. The local cytokine production and presence of inflammatory mediators, such as extracellular matrix breakdown products, influence the uneven balance of the inflammatory infiltrate phenotypes. Understanding and developing new strategies that target the pro-inflammatory phenotype could provide useful therapeutic targets for a disease with no current pharmacological intervention. PMID:26044582

Endovascular Aneurysm Repair of Acute Occlusion of Abdominal Aortic Aneurysm with Intra-Aneurysmal Dissection.

PubMed

Terai, Yasuhiko; Mitsuoka, Hiroshi; Nakai, Masanao; Goto, Shinnosuke; Miyano, Yuta; Tsuchiya, Hirokazu; Yamazaki, Fumio

2015-11-01

To report a rare case of acute abdominal aortic aneurysm (AAA) occlusion successfully treated by endovascular aneurysm repair (EVAR). An 89-year-old man complained of severe back pain and weakness in the bilateral lower extremities. Although there were neither acute ischemic signs on the brain computed tomography (CT) nor critical leg ischemia, the patient presented progressing weakness in the bilateral lower extremities and decreased sensation in the perianal and saddle area. Contrast-enhanced CT demonstrated an infrarenal AAA, the formation of an ulcer-like lesion in the aneurysmal wall, and the complete occlusion of distal AAA because of the caudal extension of intramural hematoma. Both common iliac arteries were patent because of the development of collateral vessels. The neurologic symptoms were considered to be caused by the occlusion of lumbar radicular arteries. EVAR seemed anatomically feasible, if the occlusion could be crossed by guidewires from both side of the common femoral artery. Wires easily traversed the occlusion, and the stent graft could be smoothly unwrapped and opened. The patient could recover decent iliac arterial flow. The neurovascular deficits recovered within 4 days after the procedure. Although our experience may not be reproduced in all case of AAA occlusion, EVAR warrants consideration to reduce the high mortality rate associated with the classical treatments. Copyright © 2015 Elsevier Inc. All rights reserved.

In Vivo Molecular Characterization of Abdominal Aortic Aneurysms Using Fibrin-Specific Magnetic Resonance Imaging.

PubMed

Botnar, René M; Brangsch, Julia; Reimann, Carolin; Janssen, Christian H P; Razavi, Reza; Hamm, Bernd; Makowski, Marcus R

2018-05-30

The incidence of abdominal aortic aneurysms (AAAs) will significantly increase during the next decade. Novel biomarkers, besides diameter, are needed for a better characterization of aneurysms and the estimation of the risk of rupture. Fibrin is a key protein in the formation of focal hematoma associated with the dissection of the aortic wall and the development of larger thrombi during the progression of AAAs. This study evaluated the potential of a fibrin-specific magnetic resonance (MR) probe for the in vivo characterization of the different stages of AAAs. AAAs spontaneously developed in ApoE -/- mice following the infusion of angiotensin-II (Ang-II, 1 μg/kg -1 ·per minute). An established fibrin-specific molecular MR probe (EP2104R, 10 μmol/kg -1 ) was administered after 1 to 4 weeks following Ang-II infusion (n=8 per group). All imaging experiments were performed on a clinical 3T Achieva MR system with a microscopy coil (Philips Healthcare, Netherlands). The development of AAA-associated fibrin-rich hematoma and thrombi was assessed. The high signal generated by the fibrin probe enabled high-resolution MR imaging for an accurate assessment and quantification of the relative fibrin composition of focal hematoma and thrombi. Contrast-to-noise-ratios (CNRs) and R1-relaxation rates following the administration of the fibrin probe were in good agreement with ex vivo immunohistomorphometry ( R 2 =0.83 and 0.85) and gadolinium concentrations determined by inductively coupled plasma mass spectroscopy ( R 2 =0.78 and 0.72). The fibrin-specific molecular MR probe allowed the delineation and quantification of changes in fibrin content in early and advanced AAAs. Fibrin MRI could provide a novel in vivo biomarker to improve the risk stratification of patients with aortic aneurysms. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

CFD and PTV steady flow investigation in an anatomically accurate abdominal aortic aneurysm.

PubMed

Boutsianis, Evangelos; Guala, Michele; Olgac, Ufuk; Wildermuth, Simon; Hoyer, Klaus; Ventikos, Yiannis; Poulikakos, Dimos

2009-01-01

There is considerable interest in computational and experimental flow investigations within abdominal aortic aneurysms (AAAs). This task stipulates advanced grid generation techniques and cross-validation because of the anatomical complexity. The purpose of this study is to examine the feasibility of velocity measurements by particle tracking velocimetry (PTV) in realistic AAA models. Computed tomography and rapid prototyping were combined to digitize and construct a silicone replica of a patient-specific AAA. Three-dimensional velocity measurements were acquired using PTV under steady averaged resting boundary conditions. Computational fluid dynamics (CFD) simulations were subsequently carried out with identical boundary conditions. The computational grid was created by splitting the luminal volume into manifold and nonmanifold subsections. They were filled with tetrahedral and hexahedral elements, respectively. Grid independency was tested on three successively refined meshes. Velocity differences of about 1% in all three directions existed mainly within the AAA sack. Pressure revealed similar variations, with the sparser mesh predicting larger values. PTV velocity measurements were taken along the abdominal aorta and showed good agreement with the numerical data. The results within the aneurysm neck and sack showed average velocity variations of about 5% of the mean inlet velocity. The corresponding average differences increased for all velocity components downstream the iliac bifurcation to as much as 15%. The two domains differed slightly due to flow-induced forces acting on the silicone model. Velocity quantification through narrow branches was problematic due to decreased signal to noise ratio at the larger local velocities. Computational wall pressure and shear fields are also presented. The agreement between CFD simulations and the PTV experimental data was confirmed by three-dimensional velocity comparisons at several locations within the investigated AAA anatomy indicating the feasibility of this approach.

Rapid reversal of colonic pneumatosis with restoration of mesenteric arterial supply.

PubMed

Abidali, Hussein; Cole, Lauren; Seetharam, Anil Bellur

2018-06-07

Pneumatosis cystoides intestinalis (PCI) is characterized by gas-filled cystic lesions within the wall of the large intestine and presents along a spectrum of clinical severity ranging from benign to life threatening. Etiopathogenesis is multifactorial and postulated to result from either mechanical or bacterial causes. In this report, we present a patient with chronic abdominal pain evaluated with colonoscopy revealing segmental PCI isolated to the distal colon. Further investigation revealed an abdominal aortic aneurysm (AAA) compromising the inferior mesenteric artery takeoff. Endovascular repair of the AAA resulted in clinical resolution of abdominal pain and endoscopic resolution of PCI. To our knowledge, this is the first report to document endoscopic resolution of PCI with restoration of mesenteric arterial supply, highlighting vascular insufficiency as a predisposing and reversible pathogenic mechanism.

Maintaining Elastogenicity of Mesenchymal Stem Cell-Derived Smooth Muscle Cells in Two-Dimensional Culture.

PubMed

Dahal, Shataakshi; Broekelman, Thomas; Mecham, Robert P; Ramamurthi, Anand

2018-06-01

Abdominal aortic aneurysms (AAAs) are localized expansions of the abdominal aorta that grow slowly to rupture. AAA growth is driven by irreversible elastic matrix breakdown in the aorta wall by chronically upregulated matrix metalloproteases (MMPs). Since adult vascular smooth muscle cells (SMCs) poorly regenerate elastic matrix, we previously explored utility of bone marrow mesenchymal stem cells and SMCs derived therefrom (BM-SMCs) for this purpose. One specific differentiated phenotype (cBM-SMCs) generated on a fibronectin substrate in presence of exogenous transforming growth factor-β and platelet-derived growth factor exhibited superior elastogenicity versus other phenotypes, and usefully provided proelastogenic and antiproteolytic stimuli to aneurysmal SMCs. Since in vivo cell therapy demands large cell inoculates, these derived SMCs must be propagated in vitro while maintaining their superior elastogenic, proelastogenic, and antiproteolytic characteristics. In this work, we thus investigated the culture conditions that must be provided to this propagation phase, which ensure that the differentiated SMCs maintain their phenotype and matrix regenerative benefits. Our results indicate that our BM-SMCs retain their phenotype in long-term culture even in the absence of differentiation growth factors and fibronectin substrate, but these conditions must be continued to be provided during postdifferentiation propagation if they are to maintain their superior elastic matrix deposition, crosslinking, and fiber formation properties. Our study, however, showed that cells propagated under these conditions exhibit higher expression of MMP-2, but favorably, no expression of elastolytic MMP-9. Hence, the study outcomes provide crucial guidelines to maintain phenotypic stability of cBM-SMCs during their propagation in two-dimensional culture before their delivery to the AAA wall for therapy.

Genome-wide screen identifies a novel p97/CDC-48-dependent pathway regulating ER-stress-induced gene transcription.

PubMed

Marza, Esther; Taouji, Saïd; Barroso, Kim; Raymond, Anne-Aurélie; Guignard, Léo; Bonneu, Marc; Pallares-Lupon, Néstor; Dupuy, Jean-William; Fernandez-Zapico, Martin E; Rosenbaum, Jean; Palladino, Francesca; Dupuy, Denis; Chevet, Eric

2015-03-01

The accumulation of misfolded proteins in the endoplasmic reticulum (ER) activates the Unfolded Protein Response (UPR(ER)) to restore ER homeostasis. The AAA(+) ATPase p97/CDC-48 plays key roles in ER stress by promoting both ER protein degradation and transcription of UPR(ER) genes. Although the mechanisms associated with protein degradation are now well established, the molecular events involved in the regulation of gene transcription by p97/CDC-48 remain unclear. Using a reporter-based genome-wide RNAi screen in combination with quantitative proteomic analysis in Caenorhabditis elegans, we have identified RUVB-2, a AAA(+) ATPase, as a novel repressor of a subset of UPR(ER) genes. We show that degradation of RUVB-2 by CDC-48 enhances expression of ER stress response genes through an XBP1-dependent mechanism. The functional interplay between CDC-48 and RUVB-2 in controlling transcription of select UPR(ER) genes appears conserved in human cells. Together, these results describe a novel role for p97/CDC-48, whereby its role in protein degradation is integrated with its role in regulating expression of ER stress response genes. © 2015 The Authors.

Genome-wide screen identifies a novel p97/CDC-48-dependent pathway regulating ER-stress-induced gene transcription

PubMed Central

Marza, Esther; Taouji, Saïd; Barroso, Kim; Raymond, Anne-Aurélie; Guignard, Léo; Bonneu, Marc; Pallares-Lupon, Néstor; Dupuy, Jean-William; Fernandez-Zapico, Martin E; Rosenbaum, Jean; Palladino, Francesca; Dupuy, Denis; Chevet, Eric

2015-01-01

The accumulation of misfolded proteins in the endoplasmic reticulum (ER) activates the Unfolded Protein Response (UPRER) to restore ER homeostasis. The AAA+ ATPase p97/CDC-48 plays key roles in ER stress by promoting both ER protein degradation and transcription of UPRER genes. Although the mechanisms associated with protein degradation are now well established, the molecular events involved in the regulation of gene transcription by p97/CDC-48 remain unclear. Using a reporter-based genome-wide RNAi screen in combination with quantitative proteomic analysis in Caenorhabditis elegans, we have identified RUVB-2, a AAA+ ATPase, as a novel repressor of a subset of UPRER genes. We show that degradation of RUVB-2 by CDC-48 enhances expression of ER stress response genes through an XBP1-dependent mechanism. The functional interplay between CDC-48 and RUVB-2 in controlling transcription of select UPRER genes appears conserved in human cells. Together, these results describe a novel role for p97/CDC-48, whereby its role in protein degradation is integrated with its role in regulating expression of ER stress response genes. PMID:25652260

A multiantioxidant supplementation reduces damage from ischaemia reperfusion in patients after lower torso ischaemia. A randomised trial.

PubMed

Wijnen, M H W A; Roumen, R M H; Vader, H L; Goris, R J A

2002-06-01

open repair of intra-abdominal aortic aneurysm (AAA) is associated with lower torso ischaemia and reperfusion. to examine the effect of antioxidants on the activation and sequestration of white blood cells and muscle injury during AAA repair. forty-two patients undergoing elective infrarenal aneurysm repair, were randomised to either standard therapy (22 patients) or standard therapy with additional multiantioxidant supplementation (20 patients). Vitamin E and C, Allopurinol, N-acetylcysteine and mannitol was administered perioperatively. White blood cell count (WBC), serum creatine kinase, aspartateaminotransferase, lactate and lipofuscine were measured. WBC remained higher after reperfusion in the antioxidant group (p = 0.008). CK, ASAT and lipofuscine levels were significantly lower after reperfusion in the antioxidant group (p = 0.02, p = 0.018, p = 0.017). multi-antioxidant supplementation was associated with a reduction in serum CK and ASAT after AAA repair. This is likely due to a reduction in oxidative stress and a decreased leucocyte sequestration and activation. Copyright 2002 Elsevier Science Ltd.

The major-effect quantitative trait locus CsARN6.1 encodes an AAA ATPase domain-containing protein that is associated with waterlogging stress tolerance by promoting adventitious root formation

USDA-ARS?s Scientific Manuscript database

In plants, the formation of hypocotyl-derived adventitious roots (AR) is an important morphological acclimation to waterlogging stress, but its genetic basis is largely unknown. In the present study, with combined use of bulked segregant analysis-based high throughput next-gen whole genome sequencin...

Effect of statin therapy on serum activity of proteinases and cytokines in patients with abdominal aortic aneurysm

PubMed Central

Muehling, Bernd; Oberhuber, Alexander; Schelzig, Hubert; Bischoff, Gisela; Marx, Nikolaus; Sunder-Plassmann, Ludger; Orend, Karl H

2008-01-01

Background and aims: Metalloproteinases (MMPs) are considered to be key enzymes in the pathogenesis of abdominal aortic aneurysms (AAA), with elevated levels in diseased aorta and in patient sera. Statins seem to exert an inhibitory effect on MMP activity in the aortic wall. No data exist on the effect of statins on serum activity of MMPs and inflammatory cytokines (interleukins, IL). Methods: The serum activities of MMP2 and MMP9, osteoprotegerin (OPG), and IL6 and IL10 in 63 patients undergoing elective infrarenal aneurysm repair were measured on the day before surgery. Levels were correlated to statin therapy and aneurysm diameter. Results: There was no significant difference between the two groups in the activity of circulating levels of MMP2/9, OPG, and IL6/10 in patients with infrarenal aortic aneurysm. IL6 levels in patients with AAA larger than 6 cm were significantly elevated; differences in serum activities of MMP2/9, OPG, and IL10 were not related to AAA diameter. Conclusion: Serum activities of MMP2/9, OPG, and IL6/10 are not correlated to statin therapy; IL6 levels are higher in patients with large aneurysms. Hence the effect of statin therapy in the treatment of aneurismal disease remains to be elucidated. PMID:19337556

Pre-surgical Psychological and Neuroendocrine Predictors of Psychiatric Morbidity Following Major Vascular Surgery: A Prospective Longitudinal Study

PubMed Central

King, Anthony P.; Abelson, James L.; Gholami, Bardia; Upchurch, Gilbert R.; Henke, Peter; Graham, Linda; Liberzon, Israel

2015-01-01

Objective Major life stressors, including major surgeries, are often followed by psychiatric symptoms and disorders. Prior retrospective work found abdominal-aortic aneurysm (AAA) repair is followed by increased psychiatric morbidity, which may adversely influence physical and functional recovery. Identifying risk factors prior to surgery, such as dysregulation in stress response systems, might be useful to improving preventative intervention. Methods Two hundred and sixteen patients receiving open AAA or aortofemoral bypass (AFB) surgeries, endovascular AAA repair (EVAR), or nonsurgical AAA treatment were recruited from two vascular surgery services. Psychiatric symptoms and salivary cortisol measures (waking, 4 pm, and 11 pm, before and after low-dose dexamethasone) were obtained at intake and 3 and 9 month followups. Results Following open surgeries, 18% of patients had new psychiatric disorders, compared to 4% of patients receiving EVAR or nonsurgical treatment (odds ratio = 6.0, 95% CI 1.6 - 22.1, p=.007). Having a history of major depression predicted onset of new disorders in surgical patients. Pre-surgical cortisol levels were associated with both baseline (r=.23, p<.05) and 9 month (r=.32, p<.01) psychiatric symptoms (cortisol B=1.0, SE=0.48, p<.05 in repeated measures mixed model). Conclusion Open AAA repair surgery is prospectively linked to development of psychiatric morbidity, and history of depression elevates risk. Cortisol measures prior to surgery are associated with current and future psychological functioning, suggesting potential neurobiological mechanisms that may contribute to vulnerability. These results can help identify surgical patients at risk, and point to potential targets for risk reduction interventions. PMID:26461854

Use of regional mechanical properties of abdominal aortic aneurysms to advance finite element modeling of rupture risk.

PubMed

Tierney, Áine P; Callanan, Anthony; McGloughlin, Timothy M

2012-02-01

To investigate the use of regional variations in the mechanical properties of abdominal aortic aneurysms (AAA) in finite element (FE) modeling of AAA rupture risk, which has heretofore assumed homogeneous mechanical tissue properties. Electrocardiogram-gated computed tomography scans from 3 male patients with known infrarenal AAA were used to characterize the behavior of the aneurysm in 4 different segments (posterior, anterior, and left and right lateral) at maximum diameter and above the infrarenal aorta. The elasticity of the aneurysm (circumferential cyclic strain, compliance, and the Hudetz incremental modulus) was calculated for each segment and the aneurysm as a whole. The FE analysis inclusive of prestress (pre-existing tensile stress) produced a detailed stress pattern on each of the aneurysm models under pressure loading. The 4 largest areas of stress in each region were considered in conjunction with the local regional properties of the segment to define a specific regional prestress rupture index (RPRI). In terms of elasticity, there were average reductions of 68% in circumferential cyclic strain and 63% in compliance, with a >5-fold increase in incremental modulus, between the healthy and the aneurysmal aorta for each patient. There were also regional variations in all elastic properties in each individual patient. The average difference in total stress inclusive of prestress was 59%, 67%, and 15%, respectively, for the 3 patients. Comparing the strain from FE models with the CT scans revealed an average difference in strain of 1.55% for the segmented models and 3.61% for the homogeneous models, which suggests that the segmented models more accurately reflect in vivo behavior. RPRI values were calculated for each segment for all patients. A greater understanding of the local material properties and their use in FE models is essential for greater accuracy in rupture prediction. Quantifying the regional behavior will yield insight into the changes in patient-specific aneurysms and increase understanding about the progression of aneurysmal disease.

Investigation of the Aerodynamic Performance of a DG808s UAS in Propeller Slipstream Using Computational Fluid Dynamics

NASA Astrophysics Data System (ADS)

Chandra, Yatish

Unmanned Aerial Systems (UASs) are relatively affordable and immediately available compared to commercial aircraft. Hence, their aerodynamics and design accuracies are often based on extrapolating from design standards and procedures widely used in the aerospace industry for commercial aircraft with most often, acceptable results. Engineering level software such as Advanced Aircraft Analysis (AAA) use general aviation aircraft data and later extrapolate them onto UASs for aerodynamic and flight dynamics modeling but are limited by their platform repository and relatively high Reynolds number evaluations. UASs however, are aircraft which fly at comparatively low speeds and low Reynolds number with close proximities between the components wherein such standards may not hold good. This thesis focuses on evaluating the accuracy and impact of such industry standards on the aerodynamics and flight dynamics of UASs. A DG808s UAS is chosen for the study which was previously modeled using the AAA software at The University of Kansas by the Flight Systems Team. Using the STAR-CCM+ code, performance data were compared and assessed with AAA. Aerodynamic simulations were carried out for two different configurations viz., aircraft with and without propeller slipstream effects. Data obtained for the non-powered simulations were found to be in good agreement with the AAA model. For the powered flight however, discrepancies between the AAA model and CFD data were observed with large values for the vertical tail side-force coefficient. A comparison with the system identification data from the flight tests was made to confirm and validate this vertical tail behavior with the help of rudder deflection inputs. A relationship between the propeller RPM and the aerodynamic model was established by simulating two different propeller speeds. Based on the STAR-CCM+ data and the resulting comparisons with AAA, updates necessary to the UAS aerodynamic and flight dynamics models currently used in the industry were discussed and concluded with a stress on dependency on higher fidelity methods such as Computational Fluid Dynamics.

Self-efficacy is an independent predictor for postoperative six-minute walk distance after elective open repair of abdominal aortic aneurysm.

PubMed

Hayashi, Kazuhiro; Kobayashi, Kiyonori; Shimizu, Miho; Tsuchikawa, Yohei; Kodama, Akio; Komori, Kimihiro; Nishida, Yoshihiro

2018-05-01

Open surgery is performed to treat abdominal aortic aneurysm (AAA), although the subsequent surgical stress leads to worse physical status. Preoperative self-efficacy has been reported to predict postoperative physical status after orthopedic surgery; however, it has not been sufficiently investigated in patients undergoing abdominal surgery. The purpose of the present study is to investigate the correlation between preoperative self-efficacy and postoperative six-minute walk distance (6MWD) in open AAA surgery. Seventy patients who underwent open AAA surgery were included. Functional exercise capacity was measured using preoperative and 1 week postoperative 6MWD. Self-efficacy was preoperatively measured using self-efficacy for physical activity (SEPA). The correlations of postoperative 6MWD with age, height, BMI, preoperative 6MWD, SEPA, Hospital Anxiety and Depression Scale (HADS) score, operative time, and blood loss were investigated using multivariate analysis. Single regression analysis showed that postoperative 6MWD was significantly correlated with age (r = -0.553, p ≤ 0.001), height (r = 0.292, p = 0.014), Charlson's comorbidity index (r = -0.268, p = 0.025), preoperative 6MWD (r = 0.572, p ≤ 0.001), SEPA (r = 0.586, p ≤ 0.001), and HADS-depression (r = -0.296, p = 0.013). Multiple regression analysis showed that age (p = 0.002), preoperative 6MWD (p = 0.013), and SEPA (p = 0.043) score were significantly correlated with postoperative 6MWD. Self-efficacy was an independent predictor for postoperative 6MWD after elective open AAA surgery. This suggests the importance of assessing not only physical status but also psychological factors such as self-efficacy. Implications for Rehabilitation Preoperative self-efficacy has been limited to reports after orthopedic surgery. We showed that preoperative self-efficacy predicted postoperative 6MWD after AAA surgery. Treatment to improve self-efficacy might be useful in patients receiving AAA surgery in rehabilitation.

Chronic Kidney Disease Is Positively and Diabetes Mellitus Is Negatively Associated with Abdominal Aortic Aneurysm

PubMed Central

Uchida, Haruhito A.; Kakio, Yuki; Umebayashi, Ryoko; Okuyama, Yuka; Fujii, Yasuhiro; Ozawa, Susumu; Yoshida, Masashi; Oshima, Yu; Sano, Shunji; Wada, Jun

2016-01-01

Background and Aims Chronic kidney disease (CKD) and diabetes mellitus (DM) are considered as risk factors for cardiovascular diseases. The purpose of this study was to clarify the relationship of CKD and DM with the presence of abdominal aortic aneurysm (AAA). Methods We enrolled 261 patients with AAA (AAA+) and age-and-sex matched 261 patients without AAA (AAA-) at two hospitals between 2008 and 2014, and examined the association between the risk factors and the presence of AAA. Furthermore, in order to investigate the prevalence of AAA in each group, we enrolled 1126 patients with CKD and 400 patients with DM. Results The presence of CKD in patients with AAA+ was significantly higher than that in patients with AAA- (AAA+; 65%, AAA-; 52%, P = 0.004). The presence of DM in patients with AAA+ was significantly lower than that in patients with AAA- (AAA+; 17%, AAA-; 35%, P < 0.001). A multivariate logistic regression analysis demonstrated that hypertension, ischemic heart disease and CKD were independent determinants, whereas, DM was a negatively independent determinant, for the presence of AAA. The prevalence of AAA in patients with CKD 65 years old and above was 5.1%, whereas, that in patients with DM 65 years old and above was only 0.6%. Conclusion CKD is a positively associated with the presence of AAA. In contrast, DM is a negatively associated with the presence of AAA in Japanese population. PMID:27764090

Long-term outcomes after repair of symptomatic abdominal aortic aneurysms.

PubMed

Chandra, Venita; Trang, Karen; Virgin-Downey, Whitt; Dalman, Ronald L; Mell, Matthew W

2018-04-25

Previous studies have reported increased perioperative mortality of nonruptured symptomatic abdominal aortic aneurysms (Sx-AAA) compared with asymptomatic elective AAA (E-AAA) repairs, but no long-term-outcomes have been reported. We sought to compare long-term outcomes of Sx-AAA and E-AAA after repair at a single academic institution. Patients receiving AAA repair for Sx-AAA and E-AAA from 1995 through 2015 were included. Ruptured AAA and suprarenal or thoracoabdominal AAA were excluded. Demographics, comorbidities, and operative approach were collected. Long-term mortality was the primary outcome, determined by chart review or link to Social Security Death Index. Additionally, long-term mortality and reinterventions were compared after groups were matched with nearest neighbor propensity to reduce bias. AAA repair was performed for 1054 E-AAA (383 open repair [36%], 671 endovascular aneurysm repair [EVAR] [64%]), and 139 symptomatic aneurysms (60 open repair [43%], 79 EVAR [57%]). Age (73 years vs 74 years; P = .13) and aneurysm diameter were similar between Sx-AAA and E-AAA (6.0 cm vs 5.8 cm; P = .5). The proportion of women was higher for Sx-AAA (26% vs 16%; P = .003), as was the proportion of non-Caucasians (40% vs 29%; P = .009). After propensity matching, there were no differences between groups for patient characteristics, AAA diameter, treatment modality, or comorbidities, including hypertension, coronary artery disease, congestive heart failure, diabetes, hyperlipidemia, lung disease, diabetes, renal disease, and smoking history. Women were treated for Sx-AAA at significantly smaller aortic diameters; however, compared with men (5.1 cm vs 6.3 cm; P < .001). Perioperative mortality was 5.0% for Sx-AAA and 2.3% for E-AAA (P = .055). By life-table analysis, Sx-AAA had lower 5-year (62% vs 71%) and 10-year (39% vs 51%) survivals (P = .01) compared with E-AAA for the entire cohort. Similar trends were observed for 5-year and 10-year mortality after propensity matching (63% and 40% vs 71% and 52%; P = .05). When stratified by repair type 5-year and 10-year survivals trended lower after open surgery (68% and 42% Sx-AAA vs 84% and 59% E-AAA; P = .08) but not EVAR (59% and 40% Sx-AAA vs 61% and 49% E-AAA; P = .4). Aneurysm-related reinterventions were similar for Sx-AAA and E-AAA (15% vs 14%; P = .8). Reinterventions were more common after EVAR compared with open repair (22% vs 7%, Sx-AAA P = .015; 20% vs 4% E-AAA; P = .007). Patients with Sx-AAA had lower long-term survival and similar aneurysm-related reinterventions compared with patients with E-AAA undergoing repair. Women also underwent repair for Sx-AAA at a significantly smaller size when compared with men, which emphasizes the role of gender in AAA symptomatology. Differences in long-term survival may be only partially explained by measured patient, aneurysm, and operative factors, and may reflect unmeasured social factors or suggest inherent differences in pathophysiology of Sx-AAAs. Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

[The role of estrogen in the formation and development of abdominal aortic aneurysm: experiment with rats].

PubMed

Wu, Xiao-fei; Zhang, Jian; Xin, Shi-jie; Duan, Zhi-quan; Zhang, Gong

2007-02-13

To investigate the role of estrogen in the formation and development of abdominal aortic aneurysm (AAA). Twenty male Wistar rats were randomly divided into 2 equal groups: experiment group, injected with 17-beta estradiol (E2) intraperitoneally 1 week before the establishment of AAA once a day for 3 weeks (until 2 weeks after the establishment of AAA), and underwent infusion of pancreatic elastase into the infrarenal abdominal aorta through a catheter inserted into the left common iliac artery o as to establish the AAA model, and control group, injected with normal saline intraperitoneally for 3 weeks. Two weeks after the establishment of AAA model, the rats underwent laparotomy, blood samples were collected from vena cava inferior to detect the level of E2 by radioimmunoassay and then the aneurysms were harvested to undergo immunohistochemistry and real-time PCR to detect the protein expression and mRNA expression of matrix metalloproteinase (MMP)-2 and MMP-9. The plasma E2 level of the experiment group was (28+/-6) pg/ml, significantly higher than that of the control group [(5.86+/-0.24) pg/ml, P<0.01]. The aorta dilatation rate of the experiment group was (103+/-4)%, significantly lower than that of the control group [(172+/-13)%, P<0.01]. The destruction of arterial wall, degradation of elastic fibers, and infiltration of inflammatory cells were all more severe in the control group than in the experiment group. The relative mRNA expression of MMP-2 of the experiment group was 0.07+/-0.04, significantly lower than that of the control group (0.22+/-0.07, P<0.01); and the relative mRNA expression of MMP-9 of the experiment group was 1.4+/-0.7, significantly lower than that of the control group (7.4+/-2.8, P<0.01). The protein expression of MMP-2 of the experiment group was (22+/-3)%, significantly lower than that of the control group [(50+/-12)%, P<0.01], and the protein expression of MMP-9 of the experiment group was (23+/-2)%, significantly lower than that of the control group too [(45+/-10)%, P<0.01]. Estrogen inhibits the AAA formation and development by reducing the MMP-2 and MMP-9 mRNA and protein expression and the infiltration of inflammatory cells.

Diverging effects of diabetes mellitus in patients with peripheral artery disease and abdominal aortic aneurysm and the role of advanced glycation end-products: ARTERY study - protocol for a multicentre cross-sectional study.

PubMed

de Vos, L C; Boersema, J; Hillebrands, J L; Schalkwijk, C G; Meerwaldt, R; Breek, J C; Smit, A J; Zeebregts, C J; Lefrandt, J D

2017-04-11

Diabetes mellitus is a well-defined risk factor for peripheral artery disease (PAD), but protects against the development and growth of abdominal aortic aneurysm (AAA). Diabetes mellitus is associated with arterial stiffening and peripheral arterial media sclerosis. Advanced glycation end-products (AGEs) are increased in diabetes mellitus and cardiovascular disease. AGEs are known to form cross-links between proteins and are associated with arterial stiffness. Whether AGEs contribute to the protective effects of diabetes mellitus in AAA is unknown. Therefore, the ARTERY ( A dvanced glycation end-p R oducts in patients with peripheral ar T ery dis E ase and abdominal ao R tic aneur Y sm) study is designed to evaluate the role of AGEs in the diverging effects of diabetes mellitus on AAA and PAD. This cross-sectional multicentre study will compare the amount, type and location of AGEs in the arterial wall in a total of 120 patients with AAA or PAD with and without diabetes mellitus (n=30 per subgroup). Also, local and systemic vascular parameters, including pulse wave velocity, will be measured to evaluate the association between arterial stiffness and AGEs. Finally, AGEs will be measured in serum, urine, and assessed in skin with skin autofluorescence using the AGE Reader. This study is approved by the Medical Ethics committees of University Medical Center Groningen, Martini Hospital and Medisch Spectrum Twente, the Netherlands. Study results will be disseminated through peer-reviewed journals and scientific events. trialregister.nl NTR 5363. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

AAA+ Machines of Protein Destruction in Mycobacteria.

PubMed

Alhuwaider, Adnan Ali H; Dougan, David A

2017-01-01

The bacterial cytosol is a complex mixture of macromolecules (proteins, DNA, and RNA), which collectively are responsible for an enormous array of cellular tasks. Proteins are central to most, if not all, of these tasks and as such their maintenance (commonly referred to as protein homeostasis or proteostasis) is vital for cell survival during normal and stressful conditions. The two key aspects of protein homeostasis are, (i) the correct folding and assembly of proteins (coupled with their delivery to the correct cellular location) and (ii) the timely removal of unwanted or damaged proteins from the cell, which are performed by molecular chaperones and proteases, respectively. A major class of proteins that contribute to both of these tasks are the AAA+ (ATPases associated with a variety of cellular activities) protein superfamily. Although much is known about the structure of these machines and how they function in the model Gram-negative bacterium Escherichia coli , we are only just beginning to discover the molecular details of these machines and how they function in mycobacteria. Here we review the different AAA+ machines, that contribute to proteostasis in mycobacteria. Primarily we will focus on the recent advances in the structure and function of AAA+ proteases, the substrates they recognize and the cellular pathways they control. Finally, we will discuss the recent developments related to these machines as novel drug targets.

Family Members of Patients with Abdominal Aortic Aneurysms are at Increased Risk for Aneurysms: Analysis of 618 Probands and their Families from the Liège AAA Family Study

PubMed Central

Sakalihasan, Natzi; Defraigne, Jean-Olivier; Kerstenne, Marie-Ange; Cheramy-Bien, Jean-Paul; Smelser, Diane T.; Tromp, Gerard; Kuivaniemi, Helena

2014-01-01

Background The objectives were to answer the following questions using a well-characterized population in Liège, Belgium: 1) what percentage of abdominal aortic aneurysm (AAA) patients have a positive family history for AAA, 2) what is the prevalence of AAAs among relatives of AAA patients; and 3) do familial and sporadic AAA cases differ in clinical characteristics. Methods and Results Unrelated AAA patients diagnosed at the Cardiovascular Surgery Department, University Hospital of Liège, Belgium, between 1999 and 2012 were invited to the study. A detailed family history was obtained in interviews and recorded using Progeny software. In the initial interview 62 (10%) of the 618 AAA patients reported a positive family history for AAA. We divided the 618 patients into two study groups: Group I: 296 AAA patients (268; 91% males) were followed up with computerized tomography combined with positron emission tomography, and Group II: 322 AAA patients (295; 92% males) whose families were invited to ultrasonography screening. Ultrasonography screening identified 24 new AAAs among 186 relatives (≥ 50 years) of 144 families yielding a prevalence of 13%. The highest prevalence (25%) was found among brothers. By combining the number of AAAs found by ultrasonography screening with those diagnosed previously the observed lifetime prevalence of AAA was estimated to be 32% in brothers. The familial AAA cases were more likely to have a ruptured AAA than the sporadic cases (8% vs. 2.4%; P<0.0001). Conclusions The findings confirm previously found high prevalence of AAA among brothers, support genetic contribution to AAA pathogenesis and provide rationale for targeted screening of relatives of AAA patients. PMID:24365082

Family members of patients with abdominal aortic aneurysms are at increased risk for aneurysms: analysis of 618 probands and their families from the Liège AAA Family Study.

PubMed

Sakalihasan, Natzi; Defraigne, Jean-Olivier; Kerstenne, Marie-Ange; Cheramy-Bien, Jean-Paul; Smelser, Diane T; Tromp, Gerard; Kuivaniemi, Helena

2014-05-01

The objectives were to answer the following questions with the help of a well-characterized population in Liège, Belgium: 1) what percentage of patients with abdominal aortic aneurysm (AAA) have a positive family history for AAA? 2) what is the prevalence of AAAs among relatives of patients with AAA? and 3) do familial and sporadic AAA cases differ in clinical characteristics? Patients with unrelated AAA diagnosed at the Cardiovascular Surgery Department, University Hospital of Liège, Belgium, between 1999 and 2012 were invited to the study. A detailed family history was obtained in interviews and recorded using Progeny software. We divided the 618 patients into 2 study groups: group I, 296 patients with AAA (268; 91% men) were followed up with computerized tomography combined with positron emission tomography; and group II, 322 patients with AAA (295; 92% men) whose families were invited to ultrasonographic screening. In the initial interview, 62 (10%) of the 618 patients with AAA reported a positive family history for AAA. Ultrasonographic screening identified 24 new AAAs among 186 relatives (≥50 years) of 144 families yielding a prevalence of 13%. The highest prevalence (25%) was found among brothers. By combining the number of AAAs found by ultrasonographic screening with those diagnosed previously the observed lifetime prevalence of AAA was estimated to be 32% in brothers. The familial AAA cases were more likely to have a ruptured AAA than the sporadic cases (8% vs. 2.4%; P < 0.0001). The findings confirm previously found high prevalence of AAA among brothers, support genetic contribution to AAA pathogenesis, and provide rationale for targeted screening of relatives of patients with AAA. Copyright © 2014 Elsevier Inc. All rights reserved.

The major-effect quantitative trait locus CsARN6.1 encodes an AAA ATPase domain-containing protein that is associated with waterlogging stress tolerance by promoting adventitious root formation.

PubMed

Xu, Xuewen; Ji, Jing; Xu, Qiang; Qi, Xiaohua; Weng, Yiqun; Chen, Xuehao

2018-03-01

In plants, the formation of hypocotyl-derived adventitious roots (ARs) is an important morphological acclimation to waterlogging stress; however, its genetic basis remains fragmentary. Here, through combined use of bulked segregant analysis-based whole-genome sequencing, SNP haplotyping and fine genetic mapping, we identified a candidate gene for a major-effect QTL, ARN6.1, that was responsible for waterlogging tolerance due to increased AR formation in the cucumber line Zaoer-N. Through multiple lines of evidence, we show that CsARN6.1 is the most possible candidate for ARN6.1 which encodes an AAA ATPase. The increased formation of ARs under waterlogging in Zaoer-N could be attributed to a non-synonymous SNP in the coiled-coil domain region of this gene. CsARN6.1 increases the number of ARs via its ATPase activity. Ectopic expression of CsARN6.1 in Arabidopsis resulted in better rooting ability and lateral root development in transgenic plants. Transgenic cucumber expressing the CsARN6.1 Asp allele from Zaoer-N exhibited a significant increase in number of ARs compared with the wild type expressing the allele from Pepino under waterlogging conditions. Taken together, these data support that the AAA ATPase gene CsARN6.1 has an important role in increasing cucumber AR formation and waterlogging tolerance. © 2018 The Authors The Plant Journal © 2018 John Wiley & Sons Ltd.

Developmental Localization and Methylesterification of Pectin Epitopes during Somatic Embryogenesis of Banana (Musa spp. AAA)

PubMed Central

Xu, Chunxiang; Zhao, Lu; Pan, Xiao; Šamaj, Jozef

2011-01-01

Background The plant cell walls play an important role in somatic embryogenesis and plant development. Pectins are major chemical components of primary cell walls while homogalacturonan (HG) is the most abundant pectin polysaccharide. Developmental regulation of HG methyl-esterification degree is important for cell adhesion, division and expansion, and in general for proper organ and plant development. Methodology/Principal Findings Developmental localization of pectic homogalacturonan (HG) epitopes and the (1→4)-β-D-galactan epitope of rhamnogalacturonan I (RG-I) and degree of pectin methyl-esterification (DM) were studied during somatic embryogenesis of banana (Musa spp. AAA). Histological analysis documented all major developmental stages including embryogenic cells (ECs), pre-globular, globular, pear-shaped and cotyledonary somatic embryos. Histochemical staining of extracellularly secreted pectins with ruthenium red showed the most intense staining at the surface of pre-globular, globular and pear-shaped somatic embryos. Biochemical analysis revealed developmental regulation of galacturonic acid content and DM in diverse embryogenic stages. Immunodots and immunolabeling on tissue sections revealed developmental regulation of highly methyl-esterified HG epitopes recognized by JIM7 and LM20 antibodies during somatic embryogenesis. Cell walls of pre-globular/globular and late-stage embryos contained both low methyl-esterified HG epitopes as well as partially and highly methyl-esterified ones. Extracellular matrix which covered surface of early developing embryos contained pectin epitopes recognized by 2F4, LM18, JIM5, JIM7 and LM5 antibodies. De-esterification of cell wall pectins by NaOH caused a decrease or an elimination of immunolabeling in the case of highly methyl-esterified HG epitopes. However, immunolabeling of some low methyl-esterified epitopes appeared stronger after this base treatment. Conclusions/Significance These data suggest that both low- and highly-methyl-esterified HG epitopes are developmentally regulated in diverse embryogenic stages during somatic embryogenesis. This study provides new information about pectin composition, HG methyl-esterification and developmental localization of pectin epitopes during somatic embryogenesis of banana. PMID:21826225

Abdominal Aortic Aneurysm: Evolving Controversies and Uncertainties.

PubMed

Carino, Davide; Sarac, Timur P; Ziganshin, Bulat A; Elefteriades, John A

2018-06-01

Abdominal aortic aneurysm (AAA) is defined as a permanent dilatation of the abdominal aorta that exceeds 3 cm. Most AAAs arise in the portion of abdominal aorta distal to the renal arteries and are defined as infrarenal. Most AAAs are totally asymptomatic until catastrophic rupture. The strongest predictor of AAA rupture is the diameter. Surgery is indicated to prevent rupture when the risk of rupture exceeds the risk of surgery. In this review, we aim to analyze this disease comprehensively, starting from an epidemiological perspective, exploring etiology and pathophysiology, and concluding with surgical controversies. We will pursue these goals by addressing eight specific questions regarding AAA: (1) Is the incidence of AAA increasing? (2) Are ultrasound screening programs for AAA effective? (3) What causes AAA: Genes versus environment? (4) Animal models: Are they really relevant? (5) What pathophysiology leads to AAA? (6) Indications for AAA surgery: Are surgeons over-eager to operate? (7) Elective AAA repair: Open or endovascular? (8) Emergency AAA repair: Open or endovascular?

Risk of abdominal aortic aneurysm (AAA) among male and female relatives of AAA patients.

PubMed

van de Luijtgaarden, Koen M; Rouwet, Ellen V; Hoeks, Sanne E; Stolker, Robert J; Verhagen, Hence Jm; Majoor-Krakauer, Danielle

2017-04-01

Sex affects the presentation, treatment, and outcomes of abdominal aortic aneurysm (AAA). Although AAAs are less prevalent in women, at least in the general population, women with an AAA have a poorer prognosis in comparison to men. Sex differences in the genetic predisposition for aneurysm disease remain to be established. In this study we investigated the familial risk of AAA for women compared to men. All living AAA patients included in a 2004-2012 prospective database were invited to the multidisciplinary vascular/genetics outpatient clinic between 2009 and 2012 for assessment of family history using detailed questionnaires. AAA risk for male and female relatives was calculated separately and stratified by sex of the AAA patients. Families of 568 AAA patients were investigated and 22.5% of the patients had at least one affected relative. Female relatives had a 2.8-fold and male relatives had a 1.7-fold higher risk than the estimated sex-specific population risk. Relatives of female AAA patients had a higher aneurysm risk than relatives of male patients (9.0 vs 5.9%, p = 0.022), corresponding to 5.5- and 2.0-fold increases in aneurysm risk in the female and male relatives, respectively. The risk for aortic aneurysm in relatives of AAA patients is higher than expected from population risk. The excess risk is highest for the female relatives of AAA patients and for the relatives of female AAA patients. These findings endorse targeted AAA family screening for female and male relatives of all AAA patients.

Structural insights into the Escherichia coli lysine decarboxylases and molecular determinants of interaction with the AAA+ ATPase RavA

PubMed Central

Kandiah, Eaazhisai; Carriel, Diego; Perard, Julien; Malet, Hélène; Bacia, Maria; Liu, Kaiyin; Chan, Sze W. S.; Houry, Walid A.; Ollagnier de Choudens, Sandrine; Elsen, Sylvie; Gutsche, Irina

2016-01-01

The inducible lysine decarboxylase LdcI is an important enterobacterial acid stress response enzyme whereas LdcC is its close paralogue thought to play mainly a metabolic role. A unique macromolecular cage formed by two decamers of the Escherichia coli LdcI and five hexamers of the AAA+ ATPase RavA was shown to counteract acid stress under starvation. Previously, we proposed a pseudoatomic model of the LdcI-RavA cage based on its cryo-electron microscopy map and crystal structures of an inactive LdcI decamer and a RavA monomer. We now present cryo-electron microscopy 3D reconstructions of the E. coli LdcI and LdcC, and an improved map of the LdcI bound to the LARA domain of RavA, at pH optimal for their enzymatic activity. Comparison with each other and with available structures uncovers differences between LdcI and LdcC explaining why only the acid stress response enzyme is capable of binding RavA. We identify interdomain movements associated with the pH-dependent enzyme activation and with the RavA binding. Multiple sequence alignment coupled to a phylogenetic analysis reveals that certain enterobacteria exert evolutionary pressure on the lysine decarboxylase towards the cage-like assembly with RavA, implying that this complex may have an important function under particular stress conditions. PMID:27080013

Spatial Analysis of Hospital Incidence and in Hospital Mortality of Abdominal Aortic Aneurysms in Germany: Secondary Data Analysis of Nationwide Hospital Episode (DRG) Data.

PubMed

Kuehnl, Andreas; Salvermoser, Michael; Erk, Alexander; Trenner, Matthias; Schmid, Volker; Eckstein, Hans-Henning

2018-06-01

This study aimed to analyze the spatial distribution and regional variation of the hospital incidence and in hospital mortality of abdominal aortic aneurysms (AAA) in Germany. German DRG statistics (2011-2014) were analysed. Patients with ruptured AAA (rAAA, I71.3, treated or not) and patients with non-ruptured AAA (nrAAA, I71.4, treated by open or endovascular aneurysm repair) were included. Age, sex, and risk standardisation was done using standard statistical procedures. Regional variation was quantified using systematic component of variation. To analyse spatial auto-correlation and spatial pattern, global Moran's I and Getis-Ord Gi* were calculated. A total of 50,702 cases were included. Raw hospital incidence of AAA was 15.7 per 100,000 inhabitants (nrAAA 13.1; all rAAA 2.7; treated rAAA 1.6). The standardised hospital incidence of AAA ranged from 6.3 to 30.3 per 100,000. Systematic component of variation proportion was 96% in nrAAA and 55% in treated rAAA. Incidence rates of all AAA were significantly clustered with above average values in the northwestern parts of Germany and below average values in the south and eastern regions. Standardised mortality of nrAAA ranged from 1.7% to 4.3%, with that of treated rAAA ranging from 28% to 52%. Regional variation and spatial distribution of standardised mortality was not different from random. There was significant regional variation and clustering of the hospital incidence of AAA in Germany, with higher rates in the northwest and lower rates in the southeast. There was no significant variation in standardised (age/sex/risk) mortality between counties. Copyright © 2018. Published by Elsevier B.V.

Failure of antioxidants to protect against angiotensin II-induced aortic rupture in aged apolipoprotein(E)-deficient mice.

PubMed

Jiang, F; Jones, G T; Dusting, G J

2007-11-01

Oxidative stress may be involved in the development of abdominal aortic aneurysms (AAAs). Previous studies indicate that antioxidants protect against AAA formation during chronic angiotensin (Ang) II infusion in apolipoprotein E-deficient (ApoE(0)) mice. We here examine if these protective effects also occurred in aged ApoE(0) mice. Male ApoE(0) mice (50-60 weeks) were randomly divided into 4 groups: saline, Ang II (1000 ng kg(-1) min(-1) for 4 weeks), Ang II plus antioxidants (0.1% vitamin E in food plus 0.1% vitamin C in drinking water), and Ang II plus losartan (30 mg kg(-1) day(-1)). Exogenous Ang II increased systolic blood pressure by 40 mmHg and resulted in the formation of pseudoaneurysms (rupture and extramural haematoma) in the abdominal aorta in 50% of animals. True aneurysmal dilatation was rarely observed. Antioxidants decreased systemic oxidative stress (plasma malondialdehyde), but had only minor effects on aortic rupture, relative to the complete prevention by losartan. Immunohistochemistry revealed strong matrix metalloproteinase-9 (MMP-9) expression in atherosclerotic plaques and at the sites of rupture. Antioxidants did not affect tumour necrosis factor-alpha-stimulated MMP-9 release from U937 cells. In addition, antioxidants had little effects on Ang II-induced renal dysfunction. In contrast to previous findings in younger mice, antioxidants had only minor effects on Ang II-induced aortic rupture in aged mice. Our results demonstrate that the pathological features of the aneurysmal remodelling induced by Ang II in old ApoE(0) mice are distinct from those of human AAA.

Sex- and Disease-Specific Inflammasome Signatures in Circulating Blood Leukocytes of Patients with Abdominal Aortic Aneurysm

PubMed Central

Wu, Xiaoyu; Cakmak, Sinan; Wortmann, Markus; Hakimi, Maani; Zhang, Jian; Böckler, Dittmar; Dihlmann, Susanne

2016-01-01

Male sex is a risk factor for abdominal aortic aneurysm (AAA). Within the AAA adventitia, infiltrating leukocytes express high levels of inflammasome components. To further elucidate the role of inflammatory cells in the pathogenesis of AAA, we here addressed expression and functionality of inflammasome components in peripheral blood mononuclear cells (PBMC) of AAA patients in association with sex. PBMC and plasma were isolated from 100 vascular patients, including 34 pairs of AAA patients and age/sex-matched non-AAA patients. Male PBMC were found to express significantly higher mRNA levels of AIM2, NLRP3, ASC (PYCARD), CASP1, CASP5, and IL1B (all P < 0.0001) than female PBMC. Within the male patients, PBMC of AAA patients displayed increased mRNA levels of NLRP3 (P = 0.044), CASP1 (P = 0.032) and IL1B (P = 0.0004) compared with matched non-AAA PBMC, whereas there was no difference between female AAA and non-AAA patients. The relative protein level of NLRP3 was significantly lower in PBMC lysates from all AAA patients than in matched controls (P = 0.038), whereas AIM2 and active Caspase-1 (p10) protein levels were significantly increased (P = 0.014 and P = 0.049). ELISA revealed significantly increased IL-1α (mean = 6.34 versus 0.01 pg/mL) and IL-1β plasma levels (mean = 12.07 versus 0.04 pg/mL) in AAA patients. The data indicate that male PBMC display a systemic proinflammatory state with primed inflammasomes that may contribute to AAA-pathogenesis. The AAA-specific inflammasome activation pattern suggests differential regulation of the sensors AIM2 and NLRP3 in inflammatory cells of AAA patients. PMID:27474483

A structural analysis of the AAA+ domains in Saccharomyces cerevisiae cytoplasmic dynein

PubMed Central

Gleave, Emma S.; Schmidt, Helgo; Carter, Andrew P.

2014-01-01

Dyneins are large protein complexes that act as microtubule based molecular motors. The dynein heavy chain contains a motor domain which is a member of the AAA+ protein family (ATPases Associated with diverse cellular Activities). Proteins of the AAA+ family show a diverse range of functionalities, but share a related core AAA+ domain, which often assembles into hexameric rings. Dynein is unusual because it has all six AAA+ domains linked together, in one long polypeptide. The dynein motor domain generates movement by coupling ATP driven conformational changes in the AAA+ ring to the swing of a motile element called the linker. Dynein binds to its microtubule track via a long antiparallel coiled-coil stalk that emanates from the AAA+ ring. Recently the first high resolution structures of the dynein motor domain were published. Here we provide a detailed structural analysis of the six AAA+ domains using our Saccharomycescerevisiae crystal structure. We describe how structural similarities in the dynein AAA+ domains suggest they share a common evolutionary origin. We analyse how the different AAA+ domains have diverged from each other. We discuss how this is related to the function of dynein as a motor protein and how the AAA+ domains of dynein compare to those of other AAA+ proteins. PMID:24680784

An Unusual Complication of EVAR, Spontaneous Rectus Sheath Hematoma: A Case Report

PubMed Central

Sirivanichai, Chusak

2009-01-01

Objective: To report a successful conservative management in a case of spontaneous rectus sheath hematoma (SRSH) after Endovascular Aneurysmal Repair (EVAR) of infrarenal Abdominal Aortic Aneurysm (AAA). Case Presentation: An 84-year-old woman with a 6 cm in diameter infrarenal AAA underwent EVAR at our hospital. During the procedure, intravenous heparin was administered to keep the activated clotting time around 300 seconds. One hour after the procedure, the patient complained of pain on her right side abdomen. Physical examination revealed a tender mass in the right lower abdominal wall. Laboratory studies showed a fall in hemoglobin from 12.7 g/dl to 9.3 g/dl. Ultrasound (US) examination demonstrated an 8 × 5 cm hematoma within the right rectus muscle. Follow-up US examination revealed that the hematoma had enlarged and a computed tomography (CT) examination of the lower abdomen was performed. CT scan showed a smooth-shaped mass within the layers of the anterolateral abdominal wall leading to enlargement of the right rectus abdominis muscle without signs of active bleeding. A conservative management was considered. Result: The clinical course was uneventful with a stable hemodynamic state. The patient was discharged 12 days later and was doing well at the 2 week follow-up. Conclusion: Spontaneous rectus sheath hematoma is an unusual complication of a patient on anticoagulant therapy during EVAR. A prompt radiological investigation may prevent unnecessary surgical procedures in this unusual complication. PMID:23555371

Controlled release of ascorbic acid from gelatin hydrogel attenuates abdominal aortic aneurysm formation in rat experimental abdominal aortic aneurysm model.

PubMed

Tanaka, Akiko; Hasegawa, Tomomi; Morimoto, Keisuke; Bao, Wulan; Yu, Jie; Okita, Yutaka; Tabata, Yasuhiko; Okada, Kenji

2014-09-01

Abdominal aortic aneurysms (AAAs) are associated with oxidative stress and inflammatory response. We investigated the hypothesis that the known antioxidant ascorbic acid, which can also promote elastin and collagen production by smooth muscle cells, would prevent AAA formation in a rat model. An intraluminal elastase and extraluminal calcium chloride-induced rat AAA model was used, and the animals were divided into three groups: control (group C, n = 18), the aorta wrapped with a saline-impregnated gelatin hydrogel sheet (group G, n = 18), and the aorta wrapped with a gelatin hydrogel sheet incorporating ascorbic acid (group A, n = 18). Wrapping of the sheet was completed at the end of treatment for AAA creation. The aortic dilatation ratio was measured, and aortic tissues were further examined for oxidative stress and oxidative DNA damage using biochemical and histologic techniques. Aortic dilatation at both 4 and 8 weeks was inhibited in group A (dilatation ratio [%] at 4 weeks: 186.2 ± 21.8 in group C, 152.3 ± 10.2 in group G, 126.8 ± 11.6 in group A; P < .0001; dilatation ratio [%] at 8 weeks: 219.3 ± 37.5 in group C, 194.0 ± 11.6 in group G, 145.7 ± 8.3 in group A; P = .0002). Elastin and collagen content were significantly preserved in group A (elastin, P = .0015; collagen, P < .0001). The messenger RNA expressions of matrix metalloproteinase (MMP)-9, monocyte chemotactic protein-1, interleukin-1β, and tissue necrosis factor-α (P = .0024, P < .0001, P < .0001, and P < .0001, respectively) were downregulated in group A (P = .0024), whereas tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 were both upregulated in group A (TIMP-1, P = .0014; TIMP-2, P < .0001). Gelatin zymography showed activities of pro-MMP-2, MMP-2, and MMP-9 were significantly suppressed in group C (P < .0001 for each). Reactive oxygen species expression and 8-hydroxydeoxyguanosine and cluster of differentiation 68 staining were significantly suppressed in group A (reactive oxygen species expression, P < .0001; 8-hydroxydeoxyguanosine-positive cells, P < .0001; cluster of differentiation 68 positive cells, P < .0001). Controlled release of ascorbic acid using gelatin hydrogel sheet-attenuated AAA formation through antioxidant and anti-inflammatory effect, regulation of MMP-2, TIMP-1, and TIMP-2, and preserving elastin and collagen in this animal model. Copyright © 2014 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

A Near-Wall Reynolds-Stress Closure Without Wall Normals

NASA Technical Reports Server (NTRS)

Yuan, S. P.; So, R. M. C.

1997-01-01

Turbulent wall-bounded complex flows are commonly encountered in engineering practice and are of considerable interest in a variety of industrial applications. The presence of a wall significantly affects turbulence characteristics. In addition to the wall effects, turbulent wall-bounded flows become more complicated by the presence of additional body forces (e.g. centrifugal force and Coriolis force) and complex geometry. Most near-wall Reynolds stress models are developed from a high-Reynolds-number model which assumes turbulence is homogenous (or quasi-homogenous). Near-wall modifications are proposed to include wall effects in near-wall regions. In this process, wall normals are introduced. Good predictions could be obtained by Reynolds stress models with wall normals. However, ambiguity arises when the models are applied in flows with multiple walls. Many models have been proposed to model turbulent flows. Among them, Reynolds stress models, in which turbulent stresses are obtained by solving the Reynolds stress transport equations, have been proved to be the most successful ones. To apply the Reynolds stress models to wall-bounded flows, near-wall corrections accounting for the wall effects are needed, and the resulting models are called near-wall Reynolds stress models. In most of the existing near-wall models, the near-wall corrections invoke wall normals. These wall-dependent near-wall models are difficult to implement for turbulent flows with complex geometry and may give inaccurate predictions due to the ambiguity of wall normals at corners connecting multiple walls. The objective of this study is to develop a more general and flexible near-wall Reynolds stress model without using any wall-dependent variable for wall-bounded turbulent flows. With the aid of near-wall asymptotic analysis and results of direct numerical simulation, a new near-wall Reynolds stress model (NNWRS) is formulated based on Speziale et al.'s high-Reynolds-stress model with wall-independent near-wall corrections. Moreover, only one damping function is used for flows with a wide range of Reynolds numbers to ensure that the near-wall modifications diminish away from the walls.

Lifetime Risk and Risk Factors for Abdominal Aortic Aneurysm in a 24-Year Prospective Study: The ARIC Study (Atherosclerosis Risk in Communities).

PubMed

Tang, Weihong; Yao, Lu; Roetker, Nicholas S; Alonso, Alvaro; Lutsey, Pamela L; Steenson, Carol C; Lederle, Frank A; Hunter, David W; Bengtson, Lindsay G S; Guan, Weihua; Missov, Emil; Folsom, Aaron R

2016-12-01

Abdominal aortic aneurysm (AAA) is an important vascular disease in older adults, but data on lifetime risk of AAA are sparse. We examined lifetime risk of AAA in a community-based cohort and prospectively assessed the association between midlife cardiovascular risk factors and AAAs. In ARIC study (Atherosclerosis Risk in Communities), 15 792 participants were recruited at visit 1 in 1987 to 1989 and followed up through 2013. Longitudinal smoking status was defined using smoking behavior ascertained from visit 1 (1987-1989) to visit 4 (1996-1998). We followed up participants for incident, clinical AAAs using hospital discharge diagnoses, Medicare outpatient diagnoses, or death certificates through 2011 and identified 590 incident AAAs. An abdominal ultrasound was conducted in 2011 to 2013 in 5911 surviving participants, and 75 asymptomatic AAAs were identified. We estimated the lifetime risk of AAA from the index age 45 years through 85 years of age. At age 45, the lifetime risk for AAA was 5.6% (95% confidence interval, 4.8-6.1) and was higher in men (8.2%) and current smokers (10.5%). Smokers who quit smoking between visit 1 and visit 4 had a 29% lower AAA lifetime risk compared with continuous smokers but had a higher risk than pre-visit 1 quitters. The lifetime risk of rupture or medical intervention was 1.6% (95% confidence interval, 1.2-1.8). Smoking, white race, male sex, greater height, and greater low-density lipoprotein or total cholesterol were associated with an increased risk of clinical AAA and asymptomatic AAA. At least 1 in 9 middle-aged current smokers developed AAA in their lifetime. Smoking cessation reduced the lifetime risk of AAA. © 2016 American Heart Association, Inc.

From tissue iron retention to low systemic haemoglobin levels, new pathophysiological biomarkers of human abdominal aortic aneurysm.

PubMed

Martinez-Pinna, R; Lindholt, J S; Madrigal-Matute, J; Blanco-Colio, L M; Esteban-Salan, M; Torres-Fonseca, M M; Lefebvre, T; Delbosc, S; Laustsen, J; Driss, F; Vega de Ceniga, M; Gouya, L; Weiss, G; Egido, J; Meilhac, O; Michel, J-B; Martin-Ventura, J

2014-07-03

Iron deposits are observed in tissue of abdominal aortic aneurysm (AAA) patients, although the underlying mechanisms are not completely elucidated. Therefore we explored circulating markers of iron metabolism in AAA patients, and tested if they could serve as biomarkers of AAA. Increased red blood cell (RBC)-borne iron retention and transferrin, transferrin receptor and ferritin expression was observed in AAA tissue compared to control aorta (immunohistochemistry and western blot). In contrast, decreased circulating iron, transferrin, mean corpuscular haemoglobin concentration (MCHC) and haemoglobin concentration, along with circulating RBC count, were observed in AAA patients (aortic diameter >3 cm, n=114) compared to controls (aortic diameter <3 cm, n=88) (ELISA), whereas hepcidin concentrations were increased in AAA subjects (MS/MS assay). Moreover, iron, transferrin and haemoglobin levels were negatively, and hepcidin positively, correlated with aortic diameter in AAA patients. The association of low haemoglobin with AAA presence or aortic diameter was independent of specific risk factors. Moreover, MCHC negatively correlated with thrombus area in another cohort of AAA patients (aortic diameter 3-5 cm, n=357). We found that anaemia was significantly more prevalent in AAA patients (aortic diameter >5 cm, n=8,912) compared to those in patients with atherosclerotic aorto-iliac occlusive disease (n=17,737) [adjusted odds ratio=1.77 (95% confidence interval: 1.61;1.93)]. Finally, the mortality risk among AAA patients with anaemia was increased by almost 30% [adjusted hazard ratio: 1.29 (95% confidence interval: 1.16;1.44)] as compared to AAA subjects without anaemia. In conclusion, local iron retention and altered iron recycling associated to high hepcidin and low transferrin systemic concentrations could lead to reduced circulating haemoglobin levels in AAA patients. Low haemoglobin levels are independently associated to AAA presence and clinical outcome.

[Identifying barriers to screening for abdominal aortic aneurysm in general practice: Qualitative study of 14 general practitioners in Paris].

PubMed

Niclot, J; Stansal, A; Saint-Lary, O; Lazareth, I; Priollet, P

2018-05-01

Abdominal aortic aneurysm (AAA) is a silent pathology with often fatal consequences in case of rupture. AAA screening, recommended in France and many other countries, has shown its effectiveness in reducing specific mortality. However, AAA screening rate remains insufficient. To identify barriers to AAA screening in general practice. Qualitative study carried out during 2016 among general practitioners based in Paris. Fourteen physicians were included. Most of the barriers were related to the physician: unawareness about AAA and screening recommendations, considering AAA as a secondary question not discussed with the patient, abdominal aorta not included in cardiovascular assessment, no search for a familial history of AAA, AAA considered a question for the specialist, lack of time, lack of training, numerous screenings to propose, oversight. Some barriers are related to the patient: unawareness of the pathology and family history of AAA, refusal, questioning the pertinence of the doctor's comments, failure to respect the care pathway. Others are related to AAA: source of anxiety, low prevalence, rarity of complications. The remaining barriers are related to screening: cost-benefit and risk-benefit ratios, sonographer unavailability, constraint for the patient, overmedicalization. Information and training of general practitioners about AAA must be strengthened in order to optimize AAA screening and reduce specific mortality. Copyright © 2018. Published by Elsevier Masson SAS.

Matricellular protein CCN3 mitigates abdominal aortic aneurysm

PubMed Central

Zhang, Chao; van der Voort, Dustin; Shi, Hong; Qing, Yulan; Hiraoka, Shuichi; Takemoto, Minoru; Yokote, Koutaro; Moxon, Joseph V.; Norman, Paul; Rittié, Laure; Atkins, G. Brandon; Gerson, Stanton L.; Shi, Guo-Ping; Golledge, Jonathan; Dong, Nianguo; Perbal, Bernard; Prosdocimo, Domenick A.

2016-01-01

Abdominal aortic aneurysm (AAA) is a major cause of morbidity and mortality; however, the mechanisms that are involved in disease initiation and progression are incompletely understood. Extracellular matrix proteins play an integral role in modulating vascular homeostasis in health and disease. Here, we determined that the expression of the matricellular protein CCN3 is strongly reduced in rodent AAA models, including angiotensin II–induced AAA and elastase perfusion–stimulated AAA. CCN3 levels were also reduced in human AAA biopsies compared with those in controls. In murine models of induced AAA, germline deletion of Ccn3 resulted in severe phenotypes characterized by elastin fragmentation, vessel dilation, vascular inflammation, dissection, heightened ROS generation, and smooth muscle cell loss. Conversely, overexpression of CCN3 mitigated both elastase- and angiotensin II–induced AAA formation in mice. BM transplantation experiments suggested that the AAA phenotype of CCN3-deficient mice is intrinsic to the vasculature, as AAA was not exacerbated in WT animals that received CCN3-deficient BM and WT BM did not reduce AAA severity in CCN3-deficient mice. Genetic and pharmacological approaches implicated the ERK1/2 pathway as a critical regulator of CCN3-dependent AAA development. Together, these results demonstrate that CCN3 is a nodal regulator in AAA biology and identify CCN3 as a potential therapeutic target for vascular disease. PMID:26974158

A structural analysis of the AAA+ domains in Saccharomyces cerevisiae cytoplasmic dynein.

PubMed

Gleave, Emma S; Schmidt, Helgo; Carter, Andrew P

2014-06-01

Dyneins are large protein complexes that act as microtubule based molecular motors. The dynein heavy chain contains a motor domain which is a member of the AAA+ protein family (ATPases Associated with diverse cellular Activities). Proteins of the AAA+ family show a diverse range of functionalities, but share a related core AAA+ domain, which often assembles into hexameric rings. Dynein is unusual because it has all six AAA+ domains linked together, in one long polypeptide. The dynein motor domain generates movement by coupling ATP driven conformational changes in the AAA+ ring to the swing of a motile element called the linker. Dynein binds to its microtubule track via a long antiparallel coiled-coil stalk that emanates from the AAA+ ring. Recently the first high resolution structures of the dynein motor domain were published. Here we provide a detailed structural analysis of the six AAA+ domains using our Saccharomycescerevisiae crystal structure. We describe how structural similarities in the dynein AAA+ domains suggest they share a common evolutionary origin. We analyse how the different AAA+ domains have diverged from each other. We discuss how this is related to the function of dynein as a motor protein and how the AAA+ domains of dynein compare to those of other AAA+ proteins. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Designation as “Unfit for Open Repair” Is Associated With Poor Outcomes After Endovascular Aortic Aneurysm Repair

PubMed Central

De Martino, Randall R.; Brooke, Benjamin S.; Robinson, William; Schanzer, Andres; Indes, Jeffrey E.; Wallaert, Jessica B.; Nolan, Brian W.; Cronenwett, Jack L.; Goodney, Philip P.

2014-01-01

Background Endovascular aortic aneurysm repair (EVAR) is often offered to patients with abdominal aortic aneurysms (AAAs) considered preoperatively to be unfit for open AAA repair (oAAA). This study describes the short- and long-term outcomes of patients undergoing EVAR with AAAs <6.5 cm who are considered unfit for oAAA. Methods and Results We analyzed elective EVARs for AAAs <6.5 cm diameter in the Vascular Study Group of New England (2003–2011). Patients were designated as fit or unfit for oAAA by the treating surgeon. End points included in-hospital major adverse events and long-term mortality. We identified patient characteristics associated with being unfit for open repair and predictors of survival using multivariable analyses. Of 1653 EVARs, 309 (18.7%) patients were deemed unfit for oAAA. These patients were more likely to have advanced age, cardiac disease, chronic obstructive pulmonary disease, and larger aneurysms at the time of repair (54 versus 56 mm, P=0.001). Patients unfit for oAAA had higher rates of cardiac (7.8% versus 3.1%, P<0.01) and pulmonary (3.6 versus 1.6, P<0.01) complications and worse survival rates at 5 years (61% versus 80%; log rank P<0.01) compared with those deemed fit for oAAA. Finally, patients designated as unfit for oAAA had worse survival, even adjusting for patient characteristics and aneurysm size (hazard ratio, 1.6; 95% confidence interval, 1.2–2.2; P<0.01). Conclusions In patients with AAAs <6.5 cm, designation by the operating surgeon as unfit for oAAA provides insight into both short- and long-term efficacy of EVAR. Patients unable to tolerate oAAA may not benefit from EVAR unless their risk of AAA rupture is very high. PMID:24046399

A Three-Ring Circus: Metabolism of the Three Proteogenic Aromatic Amino Acids and Their Role in the Health of Plants and Animals.

PubMed

Parthasarathy, Anutthaman; Cross, Penelope J; Dobson, Renwick C J; Adams, Lily E; Savka, Michael A; Hudson, André O

2018-01-01

Tyrosine, phenylalanine and tryptophan are the three aromatic amino acids (AAA) involved in protein synthesis. These amino acids and their metabolism are linked to the synthesis of a variety of secondary metabolites, a subset of which are involved in numerous anabolic pathways responsible for the synthesis of pigment compounds, plant hormones and biological polymers, to name a few. In addition, these metabolites derived from the AAA pathways mediate the transmission of nervous signals, quench reactive oxygen species in the brain, and are involved in the vast palette of animal coloration among others pathways. The AAA and metabolites derived from them also have integral roles in the health of both plants and animals. This review delineates the de novo biosynthesis of the AAA by microbes and plants, and the branching out of AAA metabolism into major secondary metabolic pathways in plants such as the phenylpropanoid pathway. Organisms that do not possess the enzymatic machinery for the de novo synthesis of AAA must obtain these primary metabolites from their diet. Therefore, the metabolism of AAA by the host animal and the resident microflora are important for the health of all animals. In addition, the AAA metabolite-mediated host-pathogen interactions in general, as well as potential beneficial and harmful AAA-derived compounds produced by gut bacteria are discussed. Apart from the AAA biosynthetic pathways in plants and microbes such as the shikimate pathway and the tryptophan pathway, this review also deals with AAA catabolism in plants, AAA degradation via the monoamine and kynurenine pathways in animals, and AAA catabolism via the 3-aryllactate and kynurenine pathways in animal-associated microbes. Emphasis will be placed on structural and functional aspects of several key AAA-related enzymes, such as shikimate synthase, chorismate mutase, anthranilate synthase, tryptophan synthase, tyrosine aminotransferase, dopachrome tautomerase, radical dehydratase, and type III CoA-transferase. The past development and current potential for interventions including the development of herbicides and antibiotics that target key enzymes in AAA-related pathways, as well as AAA-linked secondary metabolism leading to antimicrobials are also discussed.

A Three-Ring Circus: Metabolism of the Three Proteogenic Aromatic Amino Acids and Their Role in the Health of Plants and Animals

PubMed Central

Parthasarathy, Anutthaman; Cross, Penelope J.; Dobson, Renwick C. J.; Adams, Lily E.; Savka, Michael A.; Hudson, André O.

2018-01-01

Tyrosine, phenylalanine and tryptophan are the three aromatic amino acids (AAA) involved in protein synthesis. These amino acids and their metabolism are linked to the synthesis of a variety of secondary metabolites, a subset of which are involved in numerous anabolic pathways responsible for the synthesis of pigment compounds, plant hormones and biological polymers, to name a few. In addition, these metabolites derived from the AAA pathways mediate the transmission of nervous signals, quench reactive oxygen species in the brain, and are involved in the vast palette of animal coloration among others pathways. The AAA and metabolites derived from them also have integral roles in the health of both plants and animals. This review delineates the de novo biosynthesis of the AAA by microbes and plants, and the branching out of AAA metabolism into major secondary metabolic pathways in plants such as the phenylpropanoid pathway. Organisms that do not possess the enzymatic machinery for the de novo synthesis of AAA must obtain these primary metabolites from their diet. Therefore, the metabolism of AAA by the host animal and the resident microflora are important for the health of all animals. In addition, the AAA metabolite-mediated host-pathogen interactions in general, as well as potential beneficial and harmful AAA-derived compounds produced by gut bacteria are discussed. Apart from the AAA biosynthetic pathways in plants and microbes such as the shikimate pathway and the tryptophan pathway, this review also deals with AAA catabolism in plants, AAA degradation via the monoamine and kynurenine pathways in animals, and AAA catabolism via the 3-aryllactate and kynurenine pathways in animal-associated microbes. Emphasis will be placed on structural and functional aspects of several key AAA-related enzymes, such as shikimate synthase, chorismate mutase, anthranilate synthase, tryptophan synthase, tyrosine aminotransferase, dopachrome tautomerase, radical dehydratase, and type III CoA-transferase. The past development and current potential for interventions including the development of herbicides and antibiotics that target key enzymes in AAA-related pathways, as well as AAA-linked secondary metabolism leading to antimicrobials are also discussed. PMID:29682508

Peak AAA fatty acid homolog contaminants present in the dietary supplement l-Tryptophan associated with the onset of eosinophilia-myalgia syndrome.

PubMed

Klarskov, Klaus; Gagnon, Hugo; Racine, Mathieu; Boudreault, Pierre-Luc; Normandin, Chad; Marsault, Eric; Gleich, Gerald J; Naylor, Stephen

2018-05-22

The eosinophilia-myalgia syndrome (EMS) outbreak that occurred in the USA and elsewhere in 1989 was caused by the ingestion of Showa Denko K.K. (SD) L-tryptophan (L-Trp). "Six compounds" detected in the L-Trp were reported as case-associated contaminants. Recently the final and most statistically significant contaminant, "Peak AAA" was structurally characterized. The "compound" was actually shown to be two structural isomers resulting from condensation reactions of L-Trp with fatty acids derived from the bacterial cell membrane. They were identified as the indole C-2 anteiso (AAA 1 -343) and linear (AAA 2 -343) aliphatic chain isomers. Based on those findings, we utilized a combination of on-line HPLC-electrospray ionization mass spectrometry (LC-MS), as well as both precursor and product ion tandem mass spectrometry (MS/MS) to facilitate identification of a homologous family of condensation products related to AAA 1 -343 and AAA 2 -343. We structurally characterized eight new AAA 1 -XXX/AAA 2 -XXX contaminants, where XXX represents the integer molecular ions of all the related homologs, differing by aliphatic chain length and isomer configuration. The contaminants were derived from the following fatty acids of the bacterial cell membrane, 5-methylheptanoic acid (anteiso-C8:0) for AAA 1 -315; n-octanoic acid (n-C8:0) for AAA 2 -315; 6-methyloctanoic acid (anteiso-C9:0) for AAA 1 -329; n-nonanoic acid (n-C9:0) for AAA 2 -329; 10-methyldodecanoic acid (anteiso-C13:0) for AAA 1 -385; n-tridecanoic acid (n-C13:0) for AAA 2 -385; 11-methyltridecanoic acid (anteiso-C14:0) for AAA 1 -399; and n-tetradecanoic acid (n-C14:0) for AAA 2 -399. The concentration levels for these contaminants were estimated to be 0.1-7.9 μg / 500 mg of an individual SD L-Trp tablet or capsule The structural similarity of these homologs to case-related contaminants of Spanish Toxic Oil Syndrome (TOS) is discussed. Copyright © 2018 Elsevier B.V. All rights reserved.

AAA Foundation for Traffic Safety

MedlinePlus

... of Top Deadly Mistakes Made by Teen Drivers -- AAA AAA: Road debris causes avoidable crashes, deaths Save the ... and 500 deaths! Foundation News Stay Tuned New AAA Foundation for Traffic Safety website coming Fall 2017 ...

Aryl acylamidase activity exhibited by butyrylcholinesterase is higher in chick than in horse, but much lower than in fetal calf serum.

PubMed

Weitnauer, E; Robitzki, A; Layer, P G

1998-10-02

Several side activities have been attributed to butyrylcholinesterase (BChE), including aryl acylamidase (AAA) activity, which is an amidase-like activity with unknown physiological function splitting the artificial substrate o-nitroacetanilide. For avians, extensive developmental data have pointed to neurogenetic functions of BChE, however, a possible AAA activity of BChE has not been studied. In this study, we first compare the relative levels of AAA exhibited by BChE in whole sera from chick, fetal calves (FCS) and horse. Remarkably, FCS exhibits a 400-fold higher ratio of AAA/BChE than horse and 80-fold higher than chick serum. We then show that an immunoisolated preparation of BChE from chicken serum presents significant activity for AAA. Both in sera and with the purified enzyme, the AAA activity is fully inhibited by anticholinesterase drugs, showing that AAA activity is exclusively conveyed by the BChE molecule. Noticeably, AAA inhibition even occurs at lower drug concentrations than that of BChE activity itself. Moreover, AAA is sensitive to serotonin. These data indicate that (1) AAA is a general feature of serum BChE of vertebrates including avians, (2) AAA is effectively inhibited by cholinergic and serotonergic agents, and (3) AAA may have a developmental role, since it is much pronounced in a serum from fetal animals. Functionally, deamination of neuropeptides, a link between cholinergic and serotonergic neurotransmitter systems, and roles in lipoprotein metabolism could be relevant.

Structural basis for the ATP-independent proteolytic activity of LonB proteases and reclassification of their AAA+ modules.

PubMed

An, Young Jun; Na, Jung-Hyun; Kim, Myung-Il; Cha, Sun-Shin

2015-10-01

Lon proteases degrade defective or denature proteins as well as some folded proteins for the control of cellular protein quality. There are two types of Lon proteases, LonA and LonB. Each consists of two functional components: a protease component and an ATPase associated with various cellular activities (AAA+ module). Here, we report the 2.03 -resolution crystal structure of the isolated AAA+ module (iAAA+ module) of LonB from Thermococcus onnurineus NA1 (TonLonB). The iAAA+ module, having no bound nucleotide, adopts a conformation virtually identical to the ADP-bound conformation of AAA+ modules in the hexameric structure of TonLonB; this provides insights into the ATP-independent proteolytic activity observed in a LonB protease. Structural comparison of AAA+ modules between LonA and LonB revealed that the AAA+ modules of Lon proteases are separated into two distinct clades depending on their structural features. The AAA+ module of LonB belongs to the -H2 & Ins1 insert clade (HINS clade)- defined for the first time in this study, while the AAA+ module of LonA is a member of the HCLR clade.

Roles of conserved arginines in ATP-binding domains of AAA+ chaperone ClpB from Thermus thermophilus.

PubMed

Yamasaki, Takashi; Nakazaki, Yosuke; Yoshida, Masasuke; Watanabe, Yo-hei

2011-07-01

ClpB, a member of the expanded superfamily of ATPases associated with diverse cellular activities (AAA+), forms a ring-shaped hexamer and cooperates with the DnaK chaperone system to reactivate aggregated proteins in an ATP-dependent manner. The ClpB protomer consists of an N-terminal domain, an AAA+ module (AAA-1), a middle domain, and a second AAA+ module (AAA-2). Each AAA+ module contains highly conserved WalkerA and WalkerB motifs, and two arginines (AAA-1) or one arginine (AAA-2). Here, we investigated the roles of these arginines (Arg322, Arg323, and Arg747) of ClpB from Thermus thermophilus in the ATPase cycle and chaperone function by alanine substitution. These mutations did not affect nucleotide binding, but did inhibit the hydrolysis of the bound ATP and slow the threading of the denatured protein through the central pore of the T. thermophilus ClpB ring, which severely impaired the chaperone functions. Previously, it was demonstrated that ATP binding to the AAA-1 module induced motion of the middle domain and stabilized the ClpB hexamer. However, the arginine mutations of the AAA-1 module destabilized the ClpB hexamer, even though ATP-induced motion of the middle domain was not affected. These results indicated that the three arginines are crucial for ATP hydrolysis and chaperone activity, but not for ATP binding. In addition, the two arginines in AAA-1 and the ATP-induced motion of the middle domain independently contribute to the stabilization of the hexamer. © 2011 The Authors Journal compilation © 2011 FEBS.

Intervisceral artery origins in patients with abdominal aortic aneurysmal disease; evidence for systemic vascular remodelling.

PubMed

Bailey, Damian M; Evans, Tom G; Thomas, Kate Gower; White, Richard D; Twine, Chistopher P; Lewis, Michael H; Williams, Ian M

2016-08-01

What is the central question of this study? To what extent focal abdominal aortic aneurysmal (AAA) disease is associated with systemic remodelling of the vascular tree remains unknown. The present study examined whether anatomical differences exist between distances of the intervisceral artery origins and AAA location/size in patients with disease compared with healthy patients. What is the main finding and its importance? Intervisceral artery distances were shown to be consistently greater in AAA patients, highlighting the systemic nature of AAA disease that extends proximally to the abdominal aorta and its branches. The anatomical description of the natural variation in visceral artery origins has implications for the design of stent grafts and planning complex open aortic surgery. The initial histopathology of abdominal aortic aneurysmal (AAA) disease is atherosclerotic, later diverting towards a distinctive dilating rather than occlusive aortic phenotype. To what extent focal AAA disease is associated with systemic remodelling of the vascular tree remains unknown. The present study examined whether anatomical differences exist between the intervisceral artery origins and AAA location/size in patients with AAA disease (AAA+) relative to those without (AAA-). Preoperative contrast-enhanced computerized tomograms were reviewed in 90 consecutive AAA+ patients scheduled for open repair who underwent an infrarenal (n = 45), suprarenal (n = 26) or supracoeliac clamp (n = 19). These were compared with 39 age-matched AAA- control patients. Craniocaudal measurements were recorded from the distal origin of the coeliac artery to the superior mesenteric artery and from the origin of the superior mesenteric artery to both renal artery origins. Serial blood samples were obtained for estimation of the glomerular filtration rate before and after surgery. Intervisceral artery origins were shown to be consistently greater in AAA+ patients (P < 0.05 versus AAA-), although unrelated to AAA diameter (P > 0.05). Postoperative renal function became progressively more impaired the more proximal the clamp placement (estimated glomerular filtration rate for supracoeliac < suprarenal < infrarenal clamps, P < 0.05). These findings highlight the systemic nature of AAA disease that extends proximally to the abdominal aorta and its branches. The anatomical description of the natural variation in visceral artery origins has implications for the design of stent grafts and planning complex open aortic surgery. © 2016 The Authors. Experimental Physiology © 2016 The Physiological Society.

Biomarkers for AAA: Encouraging steps but clinical relevance still to be delivered.

PubMed

Htun, Nay Min; Peter, Karlheinz

2014-10-01

Potential biomarkers have been investigated using proteomic studies in a variety of diseases. Some biomarkers have central roles in both diagnosis and monitoring of various disorders in clinical medicine, such as troponins, brain natriuretic peptide, and C-reactive protein. Although several biomarkers have been suggested in human abdominal aortic aneurysm (AAA), reliable markers have been lacking. In this issue, Moxon et al. [Proteomics Clin Appl. 2014, 8, 762-772] undertook a broad and systematic proteomic approach toward identification of biomarkers in a commonly used AAA mouse model (AAA created by angiotensin-II infusion). In this mouse model, apolipoprotein C1 and matrix metalloproteinase-9 were identified as novel biomarkers of stable AAA. This finding represents an important step forward, toward a clinically relevant role of biomarkers in AAA. This also encourages for further studies toward the identification of biomarkers (or their combinations) that can predict AAA progression and rupture, which would represent a major progress in AAA management and would establish an AAA biomarker as a much anticipated clinical tool. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

49 CFR 173.302a - Additional requirements for shipment of nonliquefied (permanent) compressed gases in...

Code of Federal Regulations, 2011 CFR

2011-10-01

... elastic expansion was determined at the time of the last test or retest by the water jacket method. (3) Either the average wall stress or the maximum wall stress does not exceed the wall stress limitation shown in the following table: Type of steel Average wall stress limitation Maximum wall stress...

Reconsidering gender relative to risk of rupture in the contemporary management of abdominal aortic aneurysms.

PubMed

Skibba, Afshin A; Evans, James R; Hopkins, Steven P; Yoon, H Richard; Katras, Tony; Kalbfleisch, John H; Rush, Daniel S

2015-12-01

Abdominal aortic aneurysms (AAAs) may rupture at smaller diameters in women than in men, and women may be at higher risk and have poorer outcomes in elective and emergent interventions because of age and comorbidities. Practice guidelines recommending elective AAA repair at >5.5 cm are gender neutral and may not adequately reflect increased risks in women or the potential advantages of elective lower risk endovascular procedures. Patients with a diagnosis of AAA discharged from a single referral hospital during a 14-year period were identified for retrospective analysis. A total of 2121 patients with AAAs were studied, 499 women (23.5%) and 1622 men (76.5%). Women were older and had a greater incidence of hypertension, smoking, chronic obstructive pulmonary disease, dyslipidemia, and renal insufficiency. Intact AAAs in 467 women had a mean diameter of 4.4 ± 1.3 cm compared with 1538 men at 5.0 ± 1.4 cm (P < .01). The ruptured AAAs in 32 women (6.4%) had a mean diameter of 6.1 ± 1.5 cm compared with 84 men (5.2%) at 7.7 ± 1.9 cm (P < .01). Women had a twofold increased frequency of AAA rupture than men at all size intervals (P < .01). The frequency of ruptured AAAs <5.5 cm among 10 of 32 women with ruptured AAAs was 31.3%; among 7 of 84 men with ruptured AAAs, it was 8.3% (P < .01). The frequency of ruptured AAAs <5.5 cm in all 383 women with AAAs <5.5 cm was 2.6%; in 1042 men, it was 0.6% (P < .01). Of the 1211 AAA repairs, 574 (47.4%) were open aneurysm repair (OAR) and 637 (52.6%) were endovascular aneurysm repair (EVAR). Mortality after elective OAR in 475 patients of both sexes was 5.1%; for EVAR in 676 patients, mortality was 1.6% (P < .01). No differences in mortality with respect to OAR or EVAR were found between the female and male cohorts in either intact or ruptured AAAs. Women with AAAs are older and have a higher frequency of cardiovascular risk factors than men. Women rupture AAAs with a greater frequency than men at all size intervals and have a fourfold increased frequency of rupture at <5.5 cm. No differences in surgical mortality between women and men were found. Current practice guidelines for elective AAA operative intervention should be reconsidered and stratified by gender. Published by Elsevier Inc.

Variations in Abdominal Aortic Aneurysm Care: A Report From the International Consortium of Vascular Registries

PubMed Central

Sedrakyan, Art; Mao, Jialin; Venermo, Maarit; Faizer, Rumi; Debus, Sebastian; Behrendt, Christian-Alexander; Scali, Salvatore; Altreuther, Martin; Schermerhorn, Marc; Beiles, Barry; Szeberin, Zoltan; Eldrup, Nikolaj; Danielsson, Gudmundur; Thomson, Ian; Wigger, Pius; Björck, Martin; Cronenwett, Jack L.; Mani, Kevin

2016-01-01

Background: This project by the ICVR (International Consortium of Vascular Registries), a collaboration of 11 vascular surgical quality registries, was designed to evaluate international variation in the contemporary management of abdominal aortic aneurysm (AAA) with relation to recommended treatment guidelines from the Society for Vascular Surgery and the European Society for Vascular Surgery. Methods: Registry data for open and endovascular AAA repair (EVAR) during 2010 to 2013 were collected from 11 countries. Variations in patient selection and treatment were compared across countries and across centers within countries. Results: Among 51 153 patients, 86% were treated for intact AAA (iAAA) and 14% for ruptured AAA. Women constituted 18% of the entire cohort (range, 12% in Switzerland–21% in the United States; P<0.01). Intact AAAs were repaired at diameters smaller than recommended by guidelines in 31% of men (<5.5 cm; range, 6% in Iceland–41% in Germany; P<0.01) and 12% of women with iAAA (<5 cm; range, 0% in Iceland–16% in the United States; P<0.01). Overall, use of EVAR for iAAA varied from 28% in Hungary to 79% in the United States (P<0.01) and for ruptured AAA from 5% in Denmark to 52% in the United States (P<0.01). In addition to the between-country variations, significant variations were present between centers in each country in terms of EVAR use and rate of small AAA repair. Countries that more frequently treated small AAAs tended to use EVAR more frequently (trend: correlation coefficient, 0.51; P=0.14). Octogenarians made up 23% of all patients, ranging from 12% in Hungary to 29% in Australia (P<0.01). In countries with a fee-for-service reimbursement system (Australia, Germany, Switzerland, and the United States), the proportions of small AAA (33%) and octogenarians undergoing iAAA repair (25%) were higher compared with countries with a population-based reimbursement model (small AAA repair, 16%; octogenarians, 18%; P<0.01). In general, center-level variation within countries in the management of AAA was as important as variation between countries. Conclusions: Despite homogeneous guidelines from professional societies, significant variation exists in the management of AAA, most notably for iAAA diameter at repair, use of EVAR, and the treatment of elderly patients. ICVR provides an opportunity to study treatment variation across countries and to encourage optimal practice by sharing these results. PMID:27784712

Differential gene expression in human abdominal aortic aneurysm and aortic occlusive disease

PubMed Central

Moran, Corey S.; Schreurs, Charlotte; Lindeman, Jan H. N.; Walker, Philip J.; Nataatmadja, Maria; West, Malcolm; Holdt, Lesca M.; Hinterseher, Irene; Pilarsky, Christian; Golledge, Jonathan

2015-01-01

Abdominal aortic aneurysm (AAA) and aortic occlusive disease (AOD) represent common causes of morbidity and mortality in elderly populations which were previously believed to have common aetiologies. The aim of this study was to assess the gene expression in human AAA and AOD. We performed microarrays using aortic specimen obtained from 20 patients with small AAAs (≤ 55mm), 29 patients with large AAAs (> 55mm), 9 AOD patients, and 10 control aortic specimens obtained from organ donors. Some differentially expressed genes were validated by quantitative-PCR (qRT-PCR)/immunohistochemistry. We identified 840 and 1,014 differentially expressed genes in small and large AAAs, respectively. Immune-related pathways including cytokine-cytokine receptor interaction and T-cell-receptor signalling were upregulated in both small and large AAAs. Examples of validated genes included CTLA4 (2.01-fold upregulated in small AAA, P = 0.002), NKTR (2.37-and 2.66-fold upregulated in small and large AAA with P = 0.041 and P = 0.015, respectively), and CD8A (2.57-fold upregulated in large AAA, P = 0.004). 1,765 differentially expressed genes were identified in AOD. Pathways upregulated in AOD included metabolic and oxidative phosphorylation categories. The UCP2 gene was downregulated in AOD (3.73-fold downregulated, validated P = 0.017). In conclusion, the AAA and AOD transcriptomes were very different suggesting that AAA and AOD have distinct pathogenic mechanisms. PMID:25944698

Structural Insights into the Unusually Strong ATPase Activity of the AAA Domain of the Caenorhabditis elegans Fidgetin-like 1 (FIGL-1) Protein*

PubMed Central

Peng, Wentao; Lin, Zhijie; Li, Weirong; Lu, Jing; Shen, Yuequan; Wang, Chunguang

2013-01-01

The FIGL-1 (fidgetin like-1) protein is a homolog of fidgetin, a protein whose mutation leads to multiple developmental defects. The FIGL-1 protein contains an AAA (ATPase associated with various activities) domain and belongs to the AAA superfamily. However, the biological functions and developmental implications of this protein remain unknown. Here, we show that the AAA domain of the Caenorhabditis elegans FIGL-1 protein (CeFIGL-1-AAA), in clear contrast to homologous AAA domains, has an unusually high ATPase activity and forms a hexamer in solution. By determining the crystal structure of CeFIGL-1-AAA, we found that the loop linking helices α9 and α10 folds into the short helix α9a, which has an acidic surface and interacts with a positively charged surface of the neighboring subunit. Disruption of this charge interaction by mutagenesis diminishes both the ATPase activity and oligomerization capacity of the protein. Interestingly, the acidic residues in helix α9a of CeFIGL-1-AAA are not conserved in other homologous AAA domains that have relatively low ATPase activities. These results demonstrate that the sequence of CeFIGL-1-AAA has adapted to establish an intersubunit charge interaction, which contributes to its strong oligomerization and ATPase activity. These unique properties of CeFIGL-1-AAA distinguish it from other homologous proteins, suggesting that CeFIGL-1 may have a distinct biological function. PMID:23979136

Structural insights into the unusually strong ATPase activity of the AAA domain of the Caenorhabditis elegans fidgetin-like 1 (FIGL-1) protein.

PubMed

Peng, Wentao; Lin, Zhijie; Li, Weirong; Lu, Jing; Shen, Yuequan; Wang, Chunguang

2013-10-11

The FIGL-1 (fidgetin like-1) protein is a homolog of fidgetin, a protein whose mutation leads to multiple developmental defects. The FIGL-1 protein contains an AAA (ATPase associated with various activities) domain and belongs to the AAA superfamily. However, the biological functions and developmental implications of this protein remain unknown. Here, we show that the AAA domain of the Caenorhabditis elegans FIGL-1 protein (CeFIGL-1-AAA), in clear contrast to homologous AAA domains, has an unusually high ATPase activity and forms a hexamer in solution. By determining the crystal structure of CeFIGL-1-AAA, we found that the loop linking helices α9 and α10 folds into the short helix α9a, which has an acidic surface and interacts with a positively charged surface of the neighboring subunit. Disruption of this charge interaction by mutagenesis diminishes both the ATPase activity and oligomerization capacity of the protein. Interestingly, the acidic residues in helix α9a of CeFIGL-1-AAA are not conserved in other homologous AAA domains that have relatively low ATPase activities. These results demonstrate that the sequence of CeFIGL-1-AAA has adapted to establish an intersubunit charge interaction, which contributes to its strong oligomerization and ATPase activity. These unique properties of CeFIGL-1-AAA distinguish it from other homologous proteins, suggesting that CeFIGL-1 may have a distinct biological function.

Prior Radiological Investigations in 65-Year-Old Men Screened for AAA.

PubMed

Meecham, Lewis; Summerour, Virginia; Hobbs, Simon; Newman, Jeremy; Wall, Michael L

2018-05-01

The National Health Service abdominal aortic aneurysm screening programme (NAAASP) is now fully operational. Those who have previously been formally investigated for abdominal aortic aneurysm (AAA) are excluded; however, many patients undergo radiological investigation of the abdomen for other reasons. Such practices may find incidental AAA which may be eroding the performance of the NAAASP. We investigated the rates of preinvestigation before invitation to screening in our local AAA screening programme. Electronic patient records were retrospectively reviewed for all patients called between March 2013 and February 2016 in 1 local AAA screening programme. Their records were interrogated to identify any abdominal imaging within 5 years of their invitation to screening. Two thousand six hundred thirty-eight men were invited for screening; of these, 563 (21.3%) had been "prescreened". Median time between prescreening and screening was 19 months (0-60 months). Ultrasound abdomen was the most prevalent at 248 (44.0%). Two thousand two hundred forty-three (85.0%) men attended screening, and 6 (0.27%) were excluded for known AAA. Prevalence of AAA was 1.8% (n = 41). Of these, 15 (36.6%) had prior investigation with 6 (40.0%) having AAA diagnosed. Therefore, 9 (22.0%) had potential missed AAA on "prescreening" (mean diameter 35 mm [30-45], mean time lapse between investigation and screening 21.1 months [1-49]). Incidence of missed aneurysm in the "prescreened" cohort was 1.6% (9/563). Large numbers of men invited for AAA screening have undergone preinvestigation of their abdominal aorta, with 60% of the present AAA being missed. Reliance on incidental detection of AAA would leave many patients undiagnosed in the community-at risk of future rupture. Copyright © 2018 Elsevier Inc. All rights reserved.

Increased galectin-3 levels are associated with abdominal aortic aneurysm progression and inhibition of galectin-3 decreases elastase-induced AAA development.

PubMed

Fernandez-García, Carlos-Ernesto; Tarin, Carlos; Roldan-Montero, Raquel; Martinez-Lopez, Diego; Torres-Fonseca, Monica; Lindhot, Jes S; Vega de Ceniga, Melina; Egido, Jesus; Lopez-Andres, Natalia; Blanco-Colio, Luis-Miguel; Martín-Ventura, Jose-Luis

2017-11-15

Abdominal aortic aneurysm (AAA) evolution is unpredictable and no specific treatment exists for AAA, except surgery to prevent aortic rupture. Galectin-3 has been previously associated with CVD, but its potential role in AAA has not been addressed. Galectin-3 levels were increased in the plasma of AAA patients ( n =225) compared with the control group ( n =100). In addition, galectin-3 concentrations were associated with the need for surgical repair, independently of potential confounding factors. Galectin-3 mRNA and protein expression were increased in human AAA samples compared with healthy aortas. Experimental AAA in mice was induced via aortic elastase perfusion. Mice were treated intravenously with the galectin-3 inhibitor modified citrus pectin (MCP, 10 mg/kg, every other day) or saline. Similar to humans, galectin-3 serum and aortic mRNA levels were also increased in elastase-induced AAA mice compared with control mice. Mice treated with MCP showed decreased aortic dilation, as well as elastin degradation, vascular smooth muscle cell (VSMC) loss, and macrophage content at day 14 postelastase perfusion compared with control mice. The underlying mechanism(s) of the protective effect of MCP was associated with a decrease in galectin-3 and cytokine (mainly CCL5) mRNA and protein expression. Interestingly, galectin-3 induced CCL5 expression by a mechanism involving STAT3 activation in VSMC. Accordingly, MCP treatment decreased STAT3 phosphorylation in elastase-induced AAA. In conclusion, increased galectin-3 levels are associated with AAA progression, while galectin-3 inhibition decreased experimental AAA development. Our data suggest the potential role of galectin-3 as a therapeutic target in AAA. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Epidemiology and outcome of aortic aneurysms in Hong Kong.

PubMed

Cheng, Stephen W K; Ting, Albert C W; Tsang, Simon H Y

2003-02-01

The objective of this study was to determine epidemiology and mortality statistics for abdominal aortic aneurysms (AAAs) in Hong Kong. Data from three sources were obtained and analyzed: (1) Hong Kong Hospital Authority discharge statistics for 1999 and 2000; (2) a survey on aortic aneurysms in public hospitals conducted by the Working Group of Vascular Surgery; and (3) the Department of Surgery, University of Hong Kong Medical Center aortic aneurysm database. The disease pattern, distribution, and operative mortality were determined. The annual incidence of AAA in Hong Kong is 13.7 per 100,000 population and 105 per 100,000 for those aged 65 and above. About 10% of the AAAs that presented were ruptured. The mean age of the AAA patients was 74 years, with 84% of them over age 65. The operative repair rate for AAAs was low, being only 8% for intact aneurysms and 54% for ruptured ones. Overall, 45% of all aneurysm repairs were performed for a ruptured AAA. There is diverse practice between major vascular centers and smaller regional hospitals. The territory-wide operative mortality rates for intact and ruptured aneurysms were 10% (range 4-24%) and 70% (range 38--100%), respectively. There was no gender bias in the rupture and operative rates. The overall mortality was 17% for intact AAAs and 78% for ruptured AAAs. The average length of hospital stay was 19 days for elective AAA surgery and 13 days for ruptured AAAs. The number of operations in high-volume centers is increasing with a concomitant decrease in operative mortality. There are no definitive data to indicate that the incidence of AAAs is rising, but a trend toward an increasing number of operations in referral centers is noted. The low repair rates for intact AAAs and the high proportion of repairs for ruptured aneurysms suggest that AAAs are undertreated in Hong Kong.

Mitochondrial AAA proteases--towards a molecular understanding of membrane-bound proteolytic machines.

PubMed

Gerdes, Florian; Tatsuta, Takashi; Langer, Thomas

2012-01-01

Mitochondrial AAA proteases play an important role in the maintenance of mitochondrial proteostasis. They regulate and promote biogenesis of mitochondrial proteins by acting as processing enzymes and ensuring the selective turnover of misfolded proteins. Impairment of AAA proteases causes pleiotropic defects in various organisms including neurodegeneration in humans. AAA proteases comprise ring-like hexameric complexes in the mitochondrial inner membrane and are functionally conserved from yeast to man, but variations are evident in the subunit composition of orthologous enzymes. Recent structural and biochemical studies revealed how AAA proteases degrade their substrates in an ATP dependent manner. Intersubunit coordination of the ATP hydrolysis leads to an ordered ATP hydrolysis within the AAA ring, which ensures efficient substrate dislocation from the membrane and translocation to the proteolytic chamber. In this review, we summarize recent findings on the molecular mechanisms underlying the versatile functions of mitochondrial AAA proteases and their relevance to those of the other AAA+ machines. Copyright © 2011 Elsevier B.V. All rights reserved.

Science, Society, and Social Networking

NASA Astrophysics Data System (ADS)

White, K. S.; Lohwater, T.

2009-12-01

The increased use of social networking is changing the way that scientific societies interact with their members and others. The American Association for the Advancement of Science (AAAS) uses a variety of online networks to engage its members and the broader scientific community. AAAS members and non-members can interact with AAAS staff and each other on AAAS sites on Facebook, YouTube, and Twitter, as well as blogs and forums on the AAAS website (www.aaas.org). These tools allow scientists to more readily become engaged in policy by providing information on current science policy topics as well as methods of involvement. For example, members and the public can comment on policy-relevant stories from Science magazine’s ScienceInsider blog, download a weekly policy podcast, receive a weekly email update of policy issues affecting the scientific community, or watch a congressional hearing from their computer. AAAS resource websites and outreach programs, including Communicating Science (www.aaas.org/communicatingscience), Working with Congress (www.aaas.org/spp/cstc/) and Science Careers (http://sciencecareers.sciencemag.org) also provide tools for scientists to become more personally engaged in communicating their findings and involved in the policy process.

APC-PCI complex levels for screening of AAA in patients with peripheral atherosclerosis.

PubMed

Zarrouk, Moncef; Keshavarz, Kave; Lindblad, Bengt; Gottsäter, Anders

2013-11-01

To evaluate the use of activated protein C-protein C inhibitor (APC-PCI) complex levels for detection of abdominal aortic aneurysm (AAA) in patients with peripheral atherosclerotic disease (PAD). APC-PCI levels and aortic diameter evaluated in 511 PAD patients without previously known AAA followed-up concerning survival for 4.8(0.5) years. AAA was found in 13% of patients. Aortic diameter correlated (r = 0.138; p = 0.002) with APC-PCI levels which were higher (0.40[0.45] vs. 0.30[0.49] μg/l; p = 0.004) in patients with AAA. This difference persisted in multivariate analysis (p = 0.029). A threshold value of APC-PCI ≥0.15 μg/L showed a specificity of 11%, a sensitivity of 97% and a negative predictive value of 96% for an AAA diagnosis. APC-PCI levels were higher in patients with AAA, and showed high sensitivity but low specificity for the diagnosis and can therefore not be considered as a screening tool in PAD patients. An AAA prevalence of 13% in patients with PAD indicates a need for AAA screening within this population.

Research on wall shear stress considering wall roughness when shear swirling flow vibration cementing

NASA Astrophysics Data System (ADS)

Cui, Zhihua; Ai, Chi; Feng, Fuping

2017-01-01

When shear swirling flow vibration cementing, the casing is revolving periodically and eccentrically, which leads to the annulus fluid in turbulent swirling flow state. The wall shear stress is more than that in laminar flow field when conventional cementing. The paper mainly studied the wall shear stress distribution on the borehole wall when shear swirling flow vibration cementing based on the finite volume method. At the same time, the wall roughness affected and changed the turbulent flow near the borehole wall and the wall shear stress. Based on the wall function method, the paper established boundary conditions considering the wall roughness and derived the formula of the wall shear stress. The results showed that the wall roughness significantly increases the wall shear stress. However, the larger the wall roughness, the greater the thickness of mud cake, which weakening the cementing strength. Considering the effects in a comprehensive way, it is discovered that the particle size of solid phase in drilling fluid is about 0.1 mm to get better cementing quality.

AAA-ATPases in Protein Degradation

PubMed Central

Yedidi, Ravikiran S.; Wendler, Petra; Enenkel, Cordula

2017-01-01

Proteolytic machineries containing multisubunit protease complexes and AAA-ATPases play a key role in protein quality control and the regulation of protein homeostasis. In these protein degradation machineries, the proteolytically active sites are formed by either threonines or serines which are buried inside interior cavities of cylinder-shaped complexes. In eukaryotic cells, the proteasome is the most prominent protease complex harboring AAA-ATPases. To degrade protein substrates, the gates of the axial entry ports of the protease need to be open. Gate opening is accomplished by AAA-ATPases, which form a hexameric ring flanking the entry ports of the protease. Protein substrates with unstructured domains can loop into the entry ports without the assistance of AAA-ATPases. However, folded proteins require the action of AAA-ATPases to unveil an unstructured terminus or domain. Cycles of ATP binding/hydrolysis fuel the unfolding of protein substrates which are gripped by loops lining up the central pore of the AAA-ATPase ring. The AAA-ATPases pull on the unfolded polypeptide chain for translocation into the proteolytic cavity of the protease. Conformational changes within the AAA-ATPase ring and the adjacent protease chamber create a peristaltic movement for substrate degradation. The review focuses on new technologies toward the understanding of the function and structure of AAA-ATPases to achieve substrate recognition, unfolding and translocation into proteasomes in yeast and mammalian cells and into proteasome-equivalent proteases in bacteria and archaea. PMID:28676851

AAA-ATPases in Protein Degradation.

PubMed

Yedidi, Ravikiran S; Wendler, Petra; Enenkel, Cordula

2017-01-01

Proteolytic machineries containing multisubunit protease complexes and AAA-ATPases play a key role in protein quality control and the regulation of protein homeostasis. In these protein degradation machineries, the proteolytically active sites are formed by either threonines or serines which are buried inside interior cavities of cylinder-shaped complexes. In eukaryotic cells, the proteasome is the most prominent protease complex harboring AAA-ATPases. To degrade protein substrates, the gates of the axial entry ports of the protease need to be open. Gate opening is accomplished by AAA-ATPases, which form a hexameric ring flanking the entry ports of the protease. Protein substrates with unstructured domains can loop into the entry ports without the assistance of AAA-ATPases. However, folded proteins require the action of AAA-ATPases to unveil an unstructured terminus or domain. Cycles of ATP binding/hydrolysis fuel the unfolding of protein substrates which are gripped by loops lining up the central pore of the AAA-ATPase ring. The AAA-ATPases pull on the unfolded polypeptide chain for translocation into the proteolytic cavity of the protease. Conformational changes within the AAA-ATPase ring and the adjacent protease chamber create a peristaltic movement for substrate degradation. The review focuses on new technologies toward the understanding of the function and structure of AAA-ATPases to achieve substrate recognition, unfolding and translocation into proteasomes in yeast and mammalian cells and into proteasome-equivalent proteases in bacteria and archaea.

Abdominal aortic aneurysm and the association with serum levels of Homocysteine, vitamins B6, B12 and Folate

PubMed Central

Lindqvist, Markus; Hellström, Anders; Henriksson, Anders E

2012-01-01

Previous investigations have shown hyperhomocysteinemi in patients with abdominal aortic aneurysm (AAA). In the present study we evaluated the circulating level of homocysteine (Hcy) in relation to renal function, vitamins B6, B12 and folate status in AAA patients with special regard to aneurysm size, and rupture. Hcy, Creatinine, B6, B12 and folate were measured in 119 patients with AAA and 36 controls without aneurysm matched by age, gender and smoking habit. As expected there was a weak correlation between Hcy and vitamins B6, B12 or folate. We found similar levels of Hcy, B6 and folic acid in patients with nonruptured AAA compared to the control group matched by age, gender and smoking habit. There was no correlation between maximum diameter of the nonruptured AAA (n=78) and Hcy, B6 or folate. However, the present study shows a significant inverse correlation between maximum diameter of the nonruptured AAA (n=78) and B12 (r = -0.304, p=0.007) with significant higher levels in small AAA compared to large AAA. In conclusion, Hcy does not seem to be a useful biomarker in AAA disease. The unexpected finding of B12 levels correlating to aneurysm diameter warrants urgent further investigation of B12 supplement to prevent progression of small AAA. PMID:23173106

Abdominal aortic aneurysm and the association with serum levels of Homocysteine, vitamins B6, B12 and Folate.

PubMed

Lindqvist, Markus; Hellström, Anders; Henriksson, Anders E

2012-01-01

Previous investigations have shown hyperhomocysteinemi in patients with abdominal aortic aneurysm (AAA). In the present study we evaluated the circulating level of homocysteine (Hcy) in relation to renal function, vitamins B6, B12 and folate status in AAA patients with special regard to aneurysm size, and rupture. Hcy, Creatinine, B6, B12 and folate were measured in 119 patients with AAA and 36 controls without aneurysm matched by age, gender and smoking habit. As expected there was a weak correlation between Hcy and vitamins B6, B12 or folate. We found similar levels of Hcy, B6 and folic acid in patients with nonruptured AAA compared to the control group matched by age, gender and smoking habit. There was no correlation between maximum diameter of the nonruptured AAA (n=78) and Hcy, B6 or folate. However, the present study shows a significant inverse correlation between maximum diameter of the nonruptured AAA (n=78) and B12 (r = -0.304, p=0.007) with significant higher levels in small AAA compared to large AAA. In conclusion, Hcy does not seem to be a useful biomarker in AAA disease. The unexpected finding of B12 levels correlating to aneurysm diameter warrants urgent further investigation of B12 supplement to prevent progression of small AAA.

Antioxidant Vitamin C attenuates experimental abdominal aortic aneurysm development in an elastase-induced rat model.

PubMed

Shang, Tao; Liu, Zhao; Liu, Chang-jian

2014-05-01

We investigated the hypothesis that an antioxidant, Vitamin C, could attenuate abdominal aortic aneurysm (AAA) development in a rat model. An AAA model induced by intraluminal infusion was created in 36 male Sprague Dawley rats, which were randomly distributed into three groups: Sham (saline infused, placebo treated), Control (elastase infused, placebo treated), and Vitamin C (elastase infused, vitamin C treated). Vitamin C and placebo were intraperitoneally injected, initiating 1 wk before the infusion and continuing throughout the study. The aortic dilatation ratio was measured, and aortic tissues were further examined using biochemical and histologic techniques. Vitamin C attenuated the development of AAA, decreasing maximal aortic diameter by 25.8% (P < 0.05) and preserving elastin lamellae (P < 0.05). Vitamin C also decreased 8-hydroxyguanine (a marker of oxidative damage to DNA) and 8-isoprostane content (a marker of oxidative stress) in aortic tissues (P < 0.05, respectively). The proteins of matrix metalloproteinase (MMP)-2, MMP-9, and interleukin 6 were markedly downregulated (P < 0.05, respectively), accompanied with notably reduced messenger RNA expression of tumor necrosis factor-α, MMP-2/9, and interleukin 1β (P < 0.05, respectively). However, messenger RNA of tissue inhibitors of metalloproteinase-1 and tissue inhibitors of metalloproteinase-2 were both significantly upregulated in Vitamin C group. Vitamin C treatment had no significant effect on systolic blood pressure (P > 0.05). Vitamin C attenuated AAA development in an elastase-induced rat model via crucial protective effect, which was mediated by an increased level of antioxidant in cooperation with preserving elastin lamellae, inhibiting matrix-degrading proteinases and suppressing inflammatory responses. Copyright © 2014. Published by Elsevier Inc.

Abdominal aortic aneurysms: pre- and post-procedural imaging.

PubMed

Hallett, Richard L; Ullery, Brant W; Fleischmann, Dominik

2018-05-01

Abdominal aortic aneurysm (AAA) is a relatively common, potentially life-threatening disorder. Rupture of AAA is potentially catastrophic with high mortality. Intervention for AAA is indicated when the aneurysm reaches 5.0-5.5 cm or more, when symptomatic, or when increasing in size > 10 mm/year. AAA can be accurately assessed by cross-sectional imaging including computed tomography angiography and magnetic resonance angiography. Current options for intervention in AAA patients include open surgery and endovascular aneurysm repair (EVAR), with EVAR becoming more prevalent over time. Cross-sectional imaging plays a crucial role in AAA surveillance, pre-procedural assessment, and post-EVAR management. This paper will discuss the current role of imaging in the assessment of AAA patients prior to intervention, in evaluation of procedural complications, and in long-term follow-up of EVAR patients.

Time trends in hospital admissions and mortality due to abdominal aortic aneurysms in France, 2002-2013.

PubMed

Robert, M; Juillière, Y; Gabet, A; Kownator, S; Olié, V

2017-05-01

Abdominal aortic aneurysms (AAA) are serious disease with a high fatality rate but recent epidemiologic data showed a decrease of AAA mortality. Our objective was to estimate, in France, the hospitalization, inhospital mortality and mortality rates due to AAA and to analyze their trends over time. Hospitalization data were extracted from the hospital discharge summaries in the national database between 2002 and 2013. The analysis covered all patients hospitalized for AAA as a principal diagnosis. During the same period, all death certificates mentioning AAA as an initial cause of death were included in the study. Crude and standardized rates were calculated according to age and sex. Poisson regression was used to analyze the average annual percent change. In 2013, there were 8853 patients hospitalized for AAA in France (7986 unruptured and 867 ruptured). Between 2002 and 2013, the rate of patients hospitalized for unruptured AAA decreased slightly in men (-5.0%) but increased in women (+5.2%). By contrast, the rate of patients hospitalized for ruptured AAA has decreased by >20% in men and women. The proportion of endovascular treatment of unruptured AAA rose from <10% in 2005 to 35% in women and 40% in men in 2013. In 2013, 939 deaths from AAA were recorded. Mortality for this disease declined significantly from 2002 to 2013 in men and women. The unfavorable epidemiological trends in women and important evolution of the management of AAA call for an epidemiological surveillance of this disease. Copyright © 2017 Elsevier B.V. All rights reserved.

49 CFR 178.60 - Specification 8AL steel cylinders with porous fillings for acetylene.

Code of Federal Regulations, 2011 CFR

2011-10-01

... thickness; wall stress. The wall thickness/wall stress of the cylinder must conform to the following: (1) The calculated wall stress at 750 psi may not exceed 35,000 psi, or one-half of the minimum ultimate... stress must be made by the formula: S = [P(1.3D2 + 0.4d2)] / (D2 − d2) Where: S = wall stress in pounds...

Modification of tRNALys UUU by Elongator Is Essential for Efficient Translation of Stress mRNAs

PubMed Central

Sansó, Miriam; Buhne, Karin; Carmona, Mercè; Paulo, Esther; Hermand, Damien; Rodríguez-Gabriel, Miguel; Ayté, José; Leidel, Sebastian; Hidalgo, Elena

2013-01-01

The Elongator complex, including the histone acetyl transferase Sin3/Elp3, was isolated as an RNA polymerase II-interacting complex, and cells deficient in Elongator subunits display transcriptional defects. However, it has also been shown that Elongator mediates the modification of some tRNAs, modulating translation efficiency. We show here that the fission yeast Sin3/Elp3 is important for oxidative stress survival. The stress transcriptional program, governed by the Sty1-Atf1-Pcr1 pathway, is affected in mutant cells, but not severely. On the contrary, cells lacking Sin3/Elp3 cannot modify the uridine wobble nucleoside of certain tRNAs, and other tRNA modifying activities such as Ctu1-Ctu2 are also essential for normal tolerance to H2O2. In particular, a plasmid over-expressing the tRNALys UUU complements the stress-related phenotypes of Sin3/Elp3 mutant cells. We have determined that the main H2O2-dependent genes, including those coding for the transcription factors Atf1 and Pcr1, are highly expressed mRNAs containing a biased number of lysine-coding codons AAA versus AAG. Thus, their mRNAs are poorly translated after stress in cells lacking Sin3/Elp3 or Ctu2, whereas a mutated atf1 transcript with AAA-to-AAG lysine codons is efficiently translated in all strain backgrounds. Our study demonstrates that the lack of a functional Elongator complex results in stress phenotypes due to its contribution to tRNA modification and subsequent translation inefficiency of certain stress-induced, highly expressed mRNAs. These results suggest that the transcriptional defects of these strain backgrounds may be a secondary consequence of the deficient expression of a transcription factor, Atf1-Pcr1, and other components of the transcriptional machinery. PMID:23874237

Modification of tRNA(Lys) UUU by elongator is essential for efficient translation of stress mRNAs.

PubMed

Fernández-Vázquez, Jorge; Vargas-Pérez, Itzel; Sansó, Miriam; Buhne, Karin; Carmona, Mercè; Paulo, Esther; Hermand, Damien; Rodríguez-Gabriel, Miguel; Ayté, José; Leidel, Sebastian; Hidalgo, Elena

2013-01-01

The Elongator complex, including the histone acetyl transferase Sin3/Elp3, was isolated as an RNA polymerase II-interacting complex, and cells deficient in Elongator subunits display transcriptional defects. However, it has also been shown that Elongator mediates the modification of some tRNAs, modulating translation efficiency. We show here that the fission yeast Sin3/Elp3 is important for oxidative stress survival. The stress transcriptional program, governed by the Sty1-Atf1-Pcr1 pathway, is affected in mutant cells, but not severely. On the contrary, cells lacking Sin3/Elp3 cannot modify the uridine wobble nucleoside of certain tRNAs, and other tRNA modifying activities such as Ctu1-Ctu2 are also essential for normal tolerance to H2O2. In particular, a plasmid over-expressing the tRNA(Lys) UUU complements the stress-related phenotypes of Sin3/Elp3 mutant cells. We have determined that the main H2O2-dependent genes, including those coding for the transcription factors Atf1 and Pcr1, are highly expressed mRNAs containing a biased number of lysine-coding codons AAA versus AAG. Thus, their mRNAs are poorly translated after stress in cells lacking Sin3/Elp3 or Ctu2, whereas a mutated atf1 transcript with AAA-to-AAG lysine codons is efficiently translated in all strain backgrounds. Our study demonstrates that the lack of a functional Elongator complex results in stress phenotypes due to its contribution to tRNA modification and subsequent translation inefficiency of certain stress-induced, highly expressed mRNAs. These results suggest that the transcriptional defects of these strain backgrounds may be a secondary consequence of the deficient expression of a transcription factor, Atf1-Pcr1, and other components of the transcriptional machinery.

Molecularly Defined Nanostructures Based on a Novel AAA-DDD Triple Hydrogen-Bonding Motif.

PubMed

Papmeyer, Marcus; Vuilleumier, Clément A; Pavan, Giovanni M; Zhurov, Konstantin O; Severin, Kay

2016-01-26

A facile and flexible method for the synthesis of a new AAA-DDD triple hydrogen-bonding motif is described. Polytopic supramolecular building blocks with precisely oriented AAA and DDD groups are thus accessible in few steps. These building blocks were used for the assembly of large macrocycles featuring four AAA-DDD interactions and a macrobicyclic complex with a total of six AAA-DDD interactions. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Matrix metalloproteinase-2 gene variants and abdominal aortic aneurysm.

PubMed

Smallwood, L; Warrington, N; Allcock, R; van Bockxmeer, F; Palmer, L J; Iacopetta, B; Golledge, J; Norman, P E

2009-08-01

To investigate associations between two polymorphisms of the matrix metalloproteinase-2 gene (MMP2) and the incidence and progression of abdominal aortic aneurysm (AAA). Cases and controls were recruited from a trial of screening for AAAs. The association between two variants of MMP2 (-1360C>T, and +649C>T) in men with AAA (n=678) and in controls (n=659) was examined using multivariate analyses. The association with AAA expansion (n=638) was also assessed. In multivariate analyses with adjustments for multiple testing, no association between either SNP and AAA presence or expansion was detected. MMP2 -1360C>T and +649C>T variants are not risk factors for AAA.

The accuracy of combined physical examination and ultrasonography for the detection of abdominal aorta aneurysm.

PubMed

Cârstea, Doina; Streba, Letiţia Adela Maria; Glodeanu, Adina; Cârstea, A P; Vancu, Mihaela; Ninulescu, Ana-Maria

2008-01-01

Atherosclerosis is the most frequent cause in the appearance of an abdominal aorta aneurysm (AAA) and plays an important role in his development. Most AAA does not cause any symptoms, especially when talking about elderly patients, however, many of those aneurysms can be detected during physical examination. Their detection is very important because the natural evolution and the major reason in treating AAA is their tendency to rupture. We present the case of an adult man with a complex clinical pathology, but not related to the AAA. The diagnosis of the AAA has been suspicion through palpation, and the abdominal ultrasound exam confirmed it. This case is particular interesting, as the AAA requires surgical intervention, while patient's health status was poor. An essential issue is establishing the importance of the AAA screening, when there are no symptoms present. For now, there are not satisfactory studies to be used as a guide.

A multi-component parallel-plate flow chamber system for studying the effect of exercise-induced wall shear stress on endothelial cells.

PubMed

Wang, Yan-Xia; Xiang, Cheng; Liu, Bo; Zhu, Yong; Luan, Yong; Liu, Shu-Tian; Qin, Kai-Rong

2016-12-28

In vivo studies have demonstrated that reasonable exercise training can improve endothelial function. To confirm the key role of wall shear stress induced by exercise on endothelial cells, and to understand how wall shear stress affects the structure and the function of endothelial cells, it is crucial to design and fabricate an in vitro multi-component parallel-plate flow chamber system which can closely replicate exercise-induced wall shear stress waveforms in artery. The in vivo wall shear stress waveforms from the common carotid artery of a healthy volunteer in resting and immediately after 30 min acute aerobic cycling exercise were first calculated by measuring the inner diameter and the center-line blood flow velocity with a color Doppler ultrasound. According to the above in vivo wall shear stress waveforms, we designed and fabricated a parallel-plate flow chamber system with appropriate components based on a lumped parameter hemodynamics model. To validate the feasibility of this system, human umbilical vein endothelial cells (HUVECs) line were cultured within the parallel-plate flow chamber under abovementioned two types of wall shear stress waveforms and the intracellular actin microfilaments and nitric oxide (NO) production level were evaluated using fluorescence microscope. Our results show that the trends of resting and exercise-induced wall shear stress waveforms, especially the maximal, minimal and mean wall shear stress as well as oscillatory shear index, generated by the parallel-plate flow chamber system are similar to those acquired from the common carotid artery. In addition, the cellular experiments demonstrate that the actin microfilaments and the production of NO within cells exposed to the two different wall shear stress waveforms exhibit different dynamic behaviors; there are larger numbers of actin microfilaments and higher level NO in cells exposed in exercise-induced wall shear stress condition than resting wall shear stress condition. The parallel-plate flow chamber system can well reproduce wall shear stress waveforms acquired from the common carotid artery in resting and immediately after exercise states. Furthermore, it can be used for studying the endothelial cells responses under resting and exercise-induced wall shear stress environments in vitro.

High aryl acylamidase activity associated with cobra venom acetylcholinesterase: biological significance.

PubMed

Rajesh, Ramanna V; Layer, Paul G; Boopathy, Rathanam

2009-01-01

Investigation of the non-classical functions of cholinesterases (ChEs) has been the subject of interest in the past three decades. One of which is aryl acylamidase (AAA) activity associated with ChEs, but characterized in in vitro, as an enzyme, splitting the artificial substrate o-nitroacetanilide with unknown physiological function. In the present study, we have compared levels of AAA activity of AChE from different sources like goat brain, electric eel organ and from venoms of different snakes. Remarkably cobra venom showed the highest AAA activity and also high AAA/AChE ratio. Both serotonergenic and cholinergic inhibitors inhibited the cobra venom AAA activity in a concentration dependent manner, which also underlines the association of AAA with AChE of cobra venom. The study becomes interesting because of i) the cobra venom AChE exists in monomeric globular forms; ii) in Alzheimer's disease too the most abundant forms of cholinesterases are monomeric globular forms, thought to be involved in the pathogenesis of Alzheimer's disease; iii) the effect of Alzheimer's disease drugs on the AAA activity of cobra venom, indicated that AAA activity of cobra venom was more sensitive than AChE and iv) Huperzine and Tacrine showed more pronounced effect on AAA. Thus, this study elucidates the high AAA associated with cobra venom AChE may serve as one of the prominent activity to test the pharmacological effect of AD drugs, as other sources were found to have lower activity.

Genetic analysis on HLA loci in Japanese patients with abdominal aortic aneurysm.

PubMed

Sugimoto, T; Sada, M; Miyamoto, T; Yao, H

2003-08-01

autoimmunity has been proposed as one of the pathogenesis of abdominal aortic aneurysm (AAA). There is also a likelihood that when aorto-iliac occlusive disease (AIOD) coexists with AAA, some other occlusive atherosclerotic diseases, such as ischemic heart disease and cerebrovascular disease, may develop, leading to a very poor long-term prognosis. Previous studies using serological HLA typing showed that HLA-DR15 was a risk factor for AAA. In this study, we performed HLA-DNA typing by PCR to clarify the relationship between AAA and HLA genotypes in Japanese patients with AAA. In addition, we analyzed whether HLA genotypes are involved in the pathogenesis of AIOD. we examined 78 HLA genotypes of class I (HLA-A and -B) and class II (HLA-DR) and found that 60.4 and 30.4% of 49 AAA patients had HLA-A2 and HLA-B61, respectively. These frequencies were significantly higher than those in control individuals (HLA-A2, p < 0.05; HLA-B61, p < 0.005). We also found that 55.6% of nine AAA patients with AIOD had both HLA-B52 and HLA-DR B1*1502. In contrast, only 10.0% each of 40 AAA patients without AIOD showed HLA-B53 or HLA-DR B1*1502. this study showed that HLA A-2 and HLA B-61, but not HLA DR-15, were important genetic risk factors for the development of AAA among the Japanese population. We also found high frequencies of HLA-B52 and HLA-DR B1*1502 in the AAA patients with AIOD than in those without, although this must be confirmed using a larger number of AAA patients with AIOD.

Inhibition of plasmin-mediated TAFI activation may affect development but not progression of abdominal aortic aneurysms

PubMed Central

Bridge, Katherine; Revill, Charlotte; Macrae, Fraser; Bailey, Marc; Yuldasheva, Nadira; Wheatcroft, Stephen; Butlin, Roger; Foster, Richard; Scott, D. Julian; Gils, Ann; Ariёns, Robert

2017-01-01

Objective Thrombin-activatable fibrinolysis inhibitor (TAFI) reduces the breakdown of fibrin clots through its action as an indirect inhibitor of plasmin. Studies in TAFI-deficient mice have implicated a potential role for TAFI in Abdominal Aortic Aneurysm (AAA) disease. The role of TAFI inhibition on AAA formation in adult ApoE-/- mice is unknown. The aim of this paper was to investigate the effects of TAFI inhibition on AAA development and progression. Methods Using the Angiotensin II model of AAA, male ApoE-/- mice were infused with Angiotensin II 750ng/kg/min with or without a monoclonal antibody inhibitor of plasmin-mediated activation of TAFI, MA-TCK26D6, or a competitive small molecule inhibitor of TAFI, UK-396082. Results Inhibition of TAFI in the Angiotensin II model resulted in a decrease in the mortality associated with AAA rupture (from 40.0% to 16.6% with MA-TCK26D6 (log-rank Mantel Cox test p = 0.16), and 8.3% with UK-396082 (log-rank Mantel Cox test p = 0.05)). Inhibition of plasmin-mediated TAFI activation reduced the incidence of AAA from 52.4% to 30.0%. However, late treatment with MA-TCK26D6 once AAA were already established had no effect on the progression of AAA in this model. Conclusions The formation of intra-mural thrombus is responsible for the dissection and early rupture in the angiotensin II model of AAA, and this process can be prevented through inhibition of TAFI. Late treatment with a TAFI inhibitor does not prevent AAA progression. These data may indicate a role for inhibition of plasmin-mediated TAFI activation in the early stages of AAA development, but not in its progression. PMID:28472123

Combination of endovascular graft exclusion and drug therapy in AAA with hypertension or hyperglycemia.

PubMed

Wang, Dile; Qu, Bihui; He, Tao

2017-08-01

The objective of the present study was to evaluate the efficacy of combination of endovascular graft exclusion and drugs for hypertension/hyperglycemia for the treatment of abdominal aortic aneurysm (AAA). We analyzed 156 patients with AAA. Eighty-four patients were hypertensive and 72 were hyperglycemic. After endovascular graft exclusion, hypertensive patients were divided into four groups and treated with cyclopenthiazide, reserpine, propranolol, and placebo respectively. Hyperglycemic patients were divided into three groups and treated with metformin, insulin, and placebo respectively. Body temperature and peripheral blood leukocytes were measured at day 1, 2, 7, and 14 after endovascular graft exclusion. Size of AAAs, blood pressure, and blood sugar were measured again after 1 year. In hypertensive patients, the size of AAAs reduced after endovascular graft exclusion, while the combined treatments with cyclopenthiazide, reserpine, or propranolol helped to reduce blood pressure (blood pressure decrease <10 mmHg (18/21), <10 mmHg (12/21), <10 mmHg (8/21), and <10 mmHg (10/21) in the control group, cyclopenthiazide group, reserpine group, and propranolol group, respectively. AAA size decreased in the control group (P<0.001) and in the other three groups (P<0.0001). Similar results were obtained in hyperglycemic patients. The size of AAAs reduced after endovascular graft exclusion. Combined treatment with Metformin and Insulin reduced blood sugar (control, blood sugar >7.8 mmol/L (22/24), AAA size (P<0.001); metformin, blood sugar >7.8 mmol/L (14/24), AAA size (P<0.0001); insulin, blood sugar >7.8 mmol/L (11/24), AAA size (P<0.0001). Combination of endovascular graft exclusion with medicine is more effective than the former treatment alone for AAA therapy.

NASA Airborne Astronomy Ambassadors (AAA) Professional Development and NASA Connections

NASA Astrophysics Data System (ADS)

Backman, D. E.; Clark, C.; Harman, P. K.

2017-12-01

NASA's Airborne Astronomy Ambassadors (AAA) program is a three-part professional development (PD) experience for high school physics, astronomy, and earth science teachers. AAA PD consists of: (1) blended learning via webinars, asynchronous content learning, and in-person workshops, (2) a STEM immersion experience at NASA Armstrong's B703 science research aircraft facility in Palmdale, California, and (3) ongoing opportunities for connection with NASA astrophysics and planetary science Subject Matter Experts (SMEs). AAA implementation in 2016-18 involves partnerships between the SETI Institute and seven school districts in northern and southern California. AAAs in the current cohort were selected by the school districts based on criteria developed by AAA program staff working with WestEd evaluation consultants. The selected teachers were then randomly assigned by WestEd to a Group A or B to support controlled testing of student learning. Group A completed their PD during January - August 2017, then participated in NASA SOFIA science flights during fall 2017. Group B will act as a control during the 2017-18 school year, then will complete their professional development and SOFIA flights during 2018. A two-week AAA electromagnetic spectrum and multi-wavelength astronomy curriculum aligned with the Science Framework for California Public Schools and Next Generation Science Standards was developed by program staff for classroom delivery. The curriculum (as well as the AAA's pre-flight PD) capitalizes on NASA content by using "science snapshot" case studies regarding astronomy research conducted by SOFIA. AAAs also interact with NASA SMEs during flight weeks and will translate that interaction into classroom content. The AAA program will make controlled measurements of student gains in standards-based learning plus changes in student attitudes towards STEM, and observe & record the AAAs' implementation of curricular changes. Funded by NASA: NNX16AC51

Loss of MURC/Cavin-4 induces JNK and MMP-9 activity enhancement in vascular smooth muscle cells and exacerbates abdominal aortic aneurysm.

PubMed

Miyagawa, Kotaro; Ogata, Takehiro; Ueyama, Tomomi; Kasahara, Takeru; Nakanishi, Naohiko; Naito, Daisuke; Taniguchi, Takuya; Hamaoka, Tetsuro; Maruyama, Naoki; Nishi, Masahiro; Kimura, Taizo; Yamada, Hiroyuki; Aoki, Hiroki; Matoba, Satoaki

2017-06-03

Abdominal aortic aneurysm (AAA) is relatively common in elderly patients with atherosclerosis. MURC (muscle-restricted coiled-coil protein)/Cavin-4 modulating the caveolae function of muscle cells is expressed in cardiomyocytes, skeletal muscle cells and smooth muscle cells. Here, we show a novel functional role of MURC/Cavin-4 in vascular smooth muscle cells (VSMCs) and AAA development. Both wild-type (WT) and MURC/Cavin-4 knockout (MURC -/- ) mice subjected to periaortic application of CaCl 2 developed AAAs. Six weeks after CaCl 2 treatment, internal and external aortic diameters were significantly increased in MURC -/- AAAs compared with WT AAAs, which were accompanied by advanced fibrosis in the tunica media of MURC -/- AAAs. The activity of JNK and matrix metalloproteinase (MMP) -2 and -9 were increased in MURC -/- AAAs compared with WT AAAs at 5 days after CaCl 2 treatment. At 6 weeks after CaCl 2 treatment, MURC -/- AAAs exhibited attenuated JNK activity compared with WT AAAs. There was no difference in the activity of MMP-2 or -9 between saline and CaCl 2 treatments. In MURC/Cavin-4-knockdown VSMCs, TNFα-induced activity of JNK and MMP-9 was enhanced compared with control VSMCs. Furthermore, WT, MURC -/- , apolipoprotein E -/- (ApoE -/- ), and MURC/Cavin-4 and ApoE double-knockout (MURC -/- ApoE -/- ) mice were subjected to angiotensin II (Ang II) infusion. In both ApoE -/- and MURC -/- ApoE -/- mice infused for 4 weeks with Ang II, AAAs were promoted. The internal aortic diameter was significantly increased in Ang II-infused MURC -/- ApoE -/- mice compared with Ang II-infused ApoE -/- mice. In MURC/Cavin-4-knockdown VSMCs, Ang II-induced activity of JNK and MMP-9 was enhanced compared with control VSMCs. Our results suggest that MURC/Cavin-4 in VSMCs modulates AAA progression at the early stage via the activation of JNK and MMP-9. MURC/Cavin-4 is a potential therapeutic target against AAA progression. Copyright © 2017 Elsevier Inc. All rights reserved.

Abdominal aortic aneurysm screening program in Poland.

PubMed

Jawien, A; Formankiewicz, B; Derezinski, T; Migdalski, A; Brazis, P; Woda, L

Screening for abdominal aortic aneurysms (AAA) is currently recommended by several vascular societies. In countries where it has been introduced the prevalence of AAAs differed greatly and was mainly related to cigarette smoking. The screening program also had an enormous impact on the decrease of AAA ruptures and reduced mortality rate. These facts have led to the introduction of the first screening program for AAAs in Poland. The aim of the study was to determine the prevalence of AAAs among men aged 60 years and older undergoing ultrasound examination of the abdominal aorta. A single ultrasonography of the abdomen was performed to assess the aorta from the renal arteries to the bifurcation and the diameter of the aorta was measured at its widest point. The cut-off value for determining an aortic aneurysm was set at a diameter of ≥ 30 mm. All ultrasonography measurements were performed by physicians in outpatient departments throughout the Kuyavian-Pomeranian Province. Additionally, each subject had to fill out a questionnaire with demographic data, smoking habits, existing comorbidities and familial occurrence of AAAs. The study was conducted from October 2009 to November 2011. The abdominal aorta ultrasound examinations were carried out in 1556 men aged 60 years and older. The prevalence of AAA in the study population was 6.0 % (94 out of 1556). The average age of the men was 69 years (SD 6 years, range 60-92 years). In the study population 55 % of the men smoked or had smoked and 3 % were aware of the presence of AAAs in family members. There were three risk factors significantly associated with the presence of AAAs: age (p < 0.05), smoking (72.3 % vs 53.9 %, p = 0.004) and family history of AAAs (9.6 % vs 2.7 %, p = 0.017). The prevalence of AAAs among men in Poland is higher than in other European countries and the USA. The screening program for AAAs is an easy and reliable method for detecting early stages of the disease and risk factors which are the driving forces for the development of AAAs.

Vitamins and abdominal aortic aneurysm.

PubMed

Takagi, Hisato; Umemoto, Takuya

2017-02-01

To summarize the association of vitamins (B6, B12, C, D, and E) and abdominal aortic aneurysm (AAA), we reviewed clinical studies with a comprehensive literature research and meta-analytic estimates. To identify all clinical studies evaluating the association of vitamins B6/B12/C/D/E and AAA, databases including MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched through April 2015, using Web-based search engines (PubMed and OVID). For each case-control study, data regarding vitamin levels in both the AAA and control groups were used to generate standardized mean differences (SMDs) and 95% confidence intervals (CIs). Pooled analyses of the 4 case-control studies demonstrated significantly lower circulating vitamin B6 levels (SMD, -0.33; 95% CI, -0.55 to -0.11; P=0.003) but non-significantly lower vitamin B12 levels (SMD, -0.42; 95% CI, -1.09 to 0.25; P=0.22) in patients with AAA than subjects without AAA. Pooled analyses of the 2 case-control studies demonstrated significantly lower levels of circulating vitamins C (SMD, -0.71; 95% CI, -1.23 to -0.19; P=0.007) and E (SMD, -1.76; 95% CI, -2.93 to 0.60; P=0.003) in patients with AAA than subjects without AAA. Another pooled analysis of the 3 case-control studies demonstrated significantly lower circulating vitamin D (25-hydroxyvitamin D) levels (SMD, -0.25; 95% CI, -0.50 to -0.01; P=0.04) in patients with AAA than subjects without AAA. In a double-blind controlled trial, 4.0-year treatment with a high-dose folic acid and vitamin B6/B12 multivitamin in kidney transplant recipients did not reduce a rate of AAA repair despite significant reduction in homocysteine level. In another randomized, double-blind, placebo-controlled trial, 5.8-year supplementation with α-tocopherol (vitamin E) had no preventive effect on large AAA among male smokers. In clinical setting, although low circulating vitamins B6/C/D/E (not B12) levels are associated with AAA presence, vitamins B6/B12/E supplementation may not reduce AAA incidence.

Elevated ventricular wall stress disrupts cardiomyocyte t-tubule structure and calcium homeostasis.

PubMed

Frisk, Michael; Ruud, Marianne; Espe, Emil K S; Aronsen, Jan Magnus; Røe, Åsmund T; Zhang, Lili; Norseng, Per Andreas; Sejersted, Ole M; Christensen, Geir A; Sjaastad, Ivar; Louch, William E

2016-10-01

Invaginations of the cellular membrane called t-tubules are essential for maintaining efficient excitation-contraction coupling in ventricular cardiomyocytes. Disruption of t-tubule structure during heart failure has been linked to dyssynchronous, slowed Ca(2+) release and reduced power of the heartbeat. The underlying mechanism is, however, unknown. We presently investigated whether elevated ventricular wall stress triggers remodelling of t-tubule structure and function. MRI and blood pressure measurements were employed to examine regional wall stress across the left ventricle of sham-operated and failing, post-infarction rat hearts. In failing hearts, elevated left ventricular diastolic pressure and ventricular dilation resulted in markedly increased wall stress, particularly in the thin-walled region proximal to the infarct. High wall stress in this proximal zone was associated with reduced expression of the dyadic anchor junctophilin-2 and disrupted cardiomyocyte t-tubular structure. Indeed, local wall stress measurements predicted t-tubule density across sham and failing hearts. Elevated wall stress and disrupted cardiomyocyte structure in the proximal zone were also associated with desynchronized Ca(2+) release in cardiomyocytes and markedly reduced local contractility in vivo. A causative role of wall stress in promoting t-tubule remodelling was established by applying stretch to papillary muscles ex vivo under culture conditions. Loads comparable to wall stress levels observed in vivo in the proximal zone reduced expression of junctophilin-2 and promoted t-tubule loss. Elevated wall stress reduces junctophilin-2 expression and disrupts t-tubule integrity, Ca(2+) release, and contractile function. These findings provide new insight into the role of wall stress in promoting heart failure progression. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.

The Antiaircraft Journal. Volume 94, Number 6, November-December 1951

DTIC Science & Technology

1951-12-01

authorized by the Visiting Forces Act. Getting their heads together, the Yanks and Tommies have discovered each other to be pretty regular fellows...Francis A., to 3Sth AAA Brig, Ft Meade, Md. McDaniel, Otto L., to Hq Fourth Army, Ft Sam Houston, Tex. Pape, Robin B., to SOth AAA Gp, Ft Totten , NY...to 71 Sth AAA Gun Bn, Ft Totten , NJ. Kee, Pat M., to 209th AAA Gp, Indiantown Gap, Pa. Kennaman, Jack R., to SOlst AAA Gun Bn, North Richland, Wash

Using Genetic Buffering Relationships Identified in Fission Yeast To Elucidate the Molecular Pathology of Tuberous Sclerosis

DTIC Science & Technology

2016-07-01

5’-aat tat ttt ata tgg aat gag caa gta tgt ttt atc ata att gac cag ttc att tca agg acc ttc aaa aat ata cct acg aat tcg agc tcg ttt aaa c-3’), or...oTsc13 (5’-tta aga gtt cag att tgc ttt atg tgg tta ttc tgc tga agg tcc taa ttt att gac gtt gaa aaa taa agg cca cat agc gga tcc ccg ggt taa tta a-3...and oTsc14 (5’-ata aaa aaa att aat taa tga tgg caa ggc aca atc gta atc aat ctt tta att tag gac ttt tta tat gcc ctt atg gcg aat tcg agc tcg ttt aaa c

Gorham disease of the lumbar spine with an abdominal aortic aneurysm: a case report.

PubMed

Kakuta, Yohei; Iizuka, Haku; Kobayashi, Ryoichi; Iizuka, Yoichi; Takahashi, Toru; Mohara, Jun; Takagishi, Kenji

2014-01-01

Reports of Gorham disease of the lumbar spine complicated by abdominal aortic aneurysms are rare. We herein report the case of a patient with Gorham disease of the lumber spine involving an abdominal aortic aneurysm (AAA). Case report. A 49-year-old man had a 1-month history of right leg pain and severe low back pain. Plain lumbar radiography revealed an osteolytic lesion in the L4 vertebral body. Computed tomography images demonstrated the presence of an extensive osteolytic lesion in the L4 vertebral body and an AAA in front of the L4 vertebral body. The patient underwent mass resection, spinal reconstruction, and blood vessel prosthesis implantation. During surgery, it was found that the wall of the aorta had completely disappeared and was shielded by the tumor mass; therefore, we speculated that the mass in the lumbar spine had directly invaded the aorta. The patient was able to walk without right leg or low back pain 1 year after undergoing surgery. No recurrence was demonstrated in the magnetic resonance images taken 1 year and 10 months after surgery. Copyright © 2014 Elsevier Inc. All rights reserved.

Notch γ-Secretase Inhibitor Dibenzazepine Attenuates Angiotensin II-Induced Abdominal Aortic Aneurysm in ApoE Knockout Mice by Multiple Mechanisms

PubMed Central

Zheng, Yue-Hong; Li, Fang-Da; Tian, Cui; Ren, Hua-Liang; Du, Jie; Li, Hui-Hua

2013-01-01

Abdominal aortic aneurysm (AAA) is a life-threatening aortic disease in the elderly. Activation of Notch1 pathway plays a critical role in the development of AAA, but the underlying mechanisms remain poorly understood. In the present study, we explored the mechanisms by which Notch1 activation regulates angiotensin II (Ang II)-induced AAA formation and evaluated the therapeutic potential of a new Notch γ-secretase inhibitor, dibenzazepine (DBZ), for the treatment of AAA. Apolipoprotein E knockout (Apo E−/−) mice infused for 4 weeks with Ang II (1000 ng/kg/min, IP) using osmotic mini-pumps were received an intraperitoneal injection of either vehicle or 1 mg/kg/d DBZ. Notch1 signaling was activated in AAA tissue from both Ang II-infused Apo E−/− mice and human undergoing AAA repair in vivo, with increased expression of Notch intracellular domain (NICD) and its target gene Hes1, and this effect was effectively blocked by DBZ. Moreover, infusion of Ang II markedly increased the incidence and severity of AAA in Apo E−/− mice. In contrast, inhibition of Notch activation by DBZ prevented AAA formation in vivo. Furthermore, DBZ markedly prevented Ang II-stimulated accumulation of macrophages and CD4+ T cells, and ERK-mediated angiogenesis, simultaneously reversed Th2 response, in vivo. In conclusion, these findings provide new insight into the multiple mechanisms of Notch signaling involved in AAA formation and suggest that γ-secretase inhibitor DBZ might be a novel therapeutic drug for treating AAAS. PMID:24358274

Abdominal aortic aneurysm repair in New Zealand: a validation of the Australasian Vascular Audit.

PubMed

Khashram, Manar; Thomson, Ian A; Jones, Gregory T; Roake, Justin A

2017-05-01

In New Zealand (NZ), there are two major sources of operative data for abdominal aortic aneurysm (AAA) repair: the Australasian Vascular Audit (AVA) and the National Minimum Data Set (NMDS). Since the introduction of the AVA in NZ, there has not been any attempt at the validation of outcome data. The aims of this study were to report the outcomes of AAA repair and validate the AAA data captured by AVA using the NMDS. AAA procedures performed in NZ from January 2010 to December 2014 were extracted from the AVA and NMDS. Patients identified from the AVA had their survival status matched to the NMDS. Only primary AAA procedures were included for the analysis, with re-interventions and graft infections excluded. Demographical, risk factors and outcome data were used for validation. The number of patients undergoing primary AAA procedure from AVA and NMDS was 1713 and 2078, respectively. The AVA inpatient mortality for elective and rupture AAA was 1.6 and 32.2%, respectively. The NMDS 30-day mortality from AAA was 2.5 and 31.5%. Overall, 1604 patients were available for matching, and the NMDS correctly reported 98.1% of endovascular aneurysm repair and 94.2% of elective AAA repairs; however, there were major differences in comorbidity reporting between the data sets. Both data sets were incomplete, but combining administrative (NMDS) and clinical (AVA) data sets provided a more accurate assessment of mortality figures. More than 80% of AAA repairs are captured by AVA, but further work to improve compliance and comorbidity documentation is required. © 2016 Royal Australasian College of Surgeons.

Branched chain and aromatic amino acids change acutely following two medical therapies for type 2 diabetes mellitus.

PubMed

Walford, Geoffrey A; Davis, Jaclyn; Warner, A Sofia; Ackerman, Rachel J; Billings, Liana K; Chamarthi, Bindu; Fanelli, Rebecca R; Hernandez, Alicia M; Huang, Chunmei; Khan, Sabina Q; Littleton, Katherine R; Lo, Janet; McCarthy, Rita M; Rhee, Eugene P; Deik, Amy; Stolerman, Elliot; Taylor, Andrew; Hudson, Margo S; Wang, Thomas J; Altshuler, David; Grant, Richard W; Clish, Clary B; Gerszten, Robert E; Florez, Jose C

2013-12-01

Elevated circulating levels of branched chain and aromatic amino acids (BCAA/AAAs) are associated with insulin resistance and incident type 2 diabetes (T2D). BCAA/AAAs decrease acutely during an oral glucose tolerance test (OGTT), a diagnostic test for T2D. It is unknown whether changes in BCAA/AAAs also signal an early response to commonly used medical therapies for T2D. A liquid chromatography-mass spectrometry approach was used to measure BCAA/AAAs in 30 insulin sensitive (IS) and 30 insulin resistant (IR) subjects before and after: (1) one dose of a sulfonylurea medication, glipizide, 5 mg orally; (2) two days of twice daily metformin 500 mg orally; and (3) a 75-g OGTT. Percent change in BCAA/AAAs was determined after each intervention. Following glipizide, which increased insulin and decreased glucose in both subject groups, BCAA/AAAs decreased in the IS subjects only (all P<0.05). Following metformin, which decreased glucose and insulin in only the IR subjects, 4 BCAA/AAAs increased in the IR subjects at or below P=0.05, and none changed in the IS subjects. Following OGTT, which increased glucose and insulin in all subjects, BCAA/AAAs decreased in all subjects (P<0.05). BCAA/AAAs changed acutely during glipizide and metformin administration, and the magnitude and direction of change differed by the insulin resistance status of the individual and the intervention. These results indicate that BCAA/AAAs may be useful biomarkers for monitoring the early response to therapeutic interventions for T2D. © 2013.

Branched chain and aromatic amino acids change acutely following two medical therapies for type 2 diabetes mellitus

PubMed Central

Walford, Geoffrey A.; Davis, Jaclyn; Warner, A. Sofia; Ackerman, Rachel J.; Billings, Liana K.; Chamarthi, Bindu; Fanelli, Rebecca R.; Hernandez, Alicia M.; Huang, Chunmei; Khan, Sabina Q.; Littleton, Katherine R.; Lo, Janet; McCarthy, Rita M.; Rhee, Eugene P.; Deik, Amy; Stolerman, Elliot; Taylor, Andrew; Hudson, Margo S.; Wang, Thomas J.; Altshuler, David; Grant, Richard W.; Clish, Clary B.; Gerszten, Robert E.; Florez, Jose C.

2013-01-01

Objective Elevated circulating levels of branched chain and aromatic amino acids (BCAA/AAAs) are associated with insulin resistance and incident type 2 diabetes (T2D). BCAA/AAAs decrease acutely during an oral glucose tolerance test (OGTT), a diagnostic test for T2D. It is unknown whether changes in BCAA/AAAs also signal an early response to commonly used medical therapies for T2D. Materials and Methods A liquid chromatography-mass spectrometry approach was used to measure BCAA/AAAs in 30 insulin sensitive (IS) and 30 insulin resistant (IR) subjects before and after: 1) one dose of a sulfonylurea medication, glipizide, 5 mg orally; 2) two days of twice daily metformin 500 mg orally; and 3) a 75-gram OGTT. Percent change in BCAA/AAAs was determined after each intervention. Results Following glipizide, which increased insulin and decreased glucose in both subject groups, BCAA/AAAs decreased in the IS subjects only (all P<0.05). Following metformin, which decreased glucose and insulin in only the IR subjects, 4 BCAA/AAAs increased in the IR subjects at or below P=0.05, and none changed in the IS subjects. Following OGTT, which increased glucose and insulin in all subjects, BCAA/AAAs decreased in all subjects (P<0.05). Conclusions BCAA/AAAs changed acutely during glipizide and metformin administration, and the magnitude and direction of change differed by the insulin resistance status of the individual and the intervention. These results indicate that BCAA/AAAs may be useful biomarkers for monitoring the early response to therapeutic interventions for T2D. PMID:23953891

Enhancing human-animal relationships through veterinary medical instruction in animal-assisted therapy and animal-assisted activities.

PubMed

Schaffer, Caroline Brunsman

2008-01-01

Instruction in animal-assisted therapy (AAT) and animal-assisted activities (AAAs) teaches veterinary medical students to confidently and assertively maximize the benefits and minimize the risks of this union of animals and people. Instruction in AAT/AAA also addresses requirements by the American Veterinary Medical Association Council on Education that accredited schools/colleges of veterinary medicine include in their standard curriculum the topics of the human-animal bond, behavior, and the contributions of the veterinarian to the overall public and professional health care teams. Entry-level veterinarians should be prepared to: (1) assure that animals who provide AAT/AAA are healthy enough to visit nursing homes, hospitals, or other institutions; (2) promote behavior testing that selects animals who will feel safe, comfortable, and connected; (3) advise facilities regarding infection control and ways to provide a safe environment where the animals, their handlers, and the people being visited will not be injured or become ill; and (4) advocate for their patients and show compassion for their clients when animals are determined to be inappropriate participants in AAT/AAA programs. This article presents AAT/AAA terminology, ways in which veterinarians can advocate for AAT/AAA, the advantages of being involved in AAT/AAA, a model AAT/AAA practicum from Tuskegee University's School of Veterinary Medicine (TUSVM), and examples of co-curricular activities in AAT/AAA by TUSVM's student volunteers.

Lipoprotein(a) Levels in Patients With Abdominal Aortic Aneurysm.

PubMed

Kotani, Kazuhiko; Sahebkar, Amirhossein; Serban, Maria-Corina; Ursoniu, Sorin; Mikhailidis, Dimitri P; Mariscalco, Giovanni; Jones, Steven R; Martin, Seth; Blaha, Michael J; Toth, Peter P; Rizzo, Manfredi; Kostner, Karam; Rysz, Jacek; Banach, Maciej

2017-02-01

Circulating markers relevant to the development of abdominal aortic aneurysm (AAA) are currently required. Lipoprotein(a), Lp(a), is considered a candidate marker associated with the presence of AAA. The present meta-analysis aimed to evaluate the association between circulating Lp(a) levels and the presence of AAA. The PubMed-based search was conducted up to April 30, 2015, to identify the studies focusing on Lp(a) levels in patients with AAA and controls. Quantitative data synthesis was performed using a random effects model, with standardized mean difference (SMD) and 95% confidence interval (CI) as summary statistics. Overall, 9 studies were identified. After a combined analysis, patients with AAA were found to have a significantly higher level of Lp(a) compared to the controls (SMD: 0.87, 95% CI: 0.41-1.33, P < .001). This result remained robust in the sensitivity analysis, and its significance was not influenced after omitting each of the included studies from the meta-analysis. The present meta-analysis confirmed a higher level of circulating Lp(a) in patients with AAA compared to controls. High Lp(a) levels can be associated with the presence of AAA, and Lp(a) may be a marker in screening for AAA. Further studies are needed to establish the clinical utility of measuring Lp(a) in the prevention and management of AAA.

Understanding the molecular mechanism of aryl acylamidase activity of acetylcholinesterase - An in silico study.

PubMed

Chinnadurai, Raj Kumar; Saravanaraman, Ponne; Boopathy, Rathanam

2015-08-15

Acetylcholinesterase (AChE) exhibits two different activities, namely esterase and aryl acylamidase (AAA). Unlike esterase, AAA activity of AChE is inhibited by the active site inhibitors while remaining unaffected by the peripheral anionic site inhibitors. This differential inhibitory pattern of active and peripheral anionic site inhibitors on the AAA activity remains unanswered. To answer this, we investigated the mechanism of binding and trafficking of AAA substrates using in silico tools. Molecular docking of serotonin and AAA substrates (o-nitroacetanilide, and o-nitrotrifluoroacetanilide,) onto AChE shows that these compounds bind at the side door of AChE. Thus, we conceived that the AAA substrates prefer the side door to reach the active site for their catalysis. Further, steered molecular dynamics simulations show that the force required for binding and trafficking of the AAA substrate through the side door is comparatively lesser than their dissociation (900kJ/mol/nm). Among the two substrates, o-nitrotrifluoroacetanilide required lesser force (380kJ/mol/nm) than o-nitroacetanilide the (550kJ/mol/nm) for its binding, thus validating o-nitrotrifluoroacetanilide as a better substrate. With these observations, we resolve that the AAA activity of AChE is mediated through its side door. Therefore, binding of PAS inhibitors at the main door of AChE remain ineffective against AAA activity. Copyright © 2015 Elsevier Inc. All rights reserved.

Introducing AAA-MS, a rapid and sensitive method for amino acid analysis using isotope dilution and high-resolution mass spectrometry.

PubMed

Louwagie, Mathilde; Kieffer-Jaquinod, Sylvie; Dupierris, Véronique; Couté, Yohann; Bruley, Christophe; Garin, Jérôme; Dupuis, Alain; Jaquinod, Michel; Brun, Virginie

2012-07-06

Accurate quantification of pure peptides and proteins is essential for biotechnology, clinical chemistry, proteomics, and systems biology. The reference method to quantify peptides and proteins is amino acid analysis (AAA). This consists of an acidic hydrolysis followed by chromatographic separation and spectrophotometric detection of amino acids. Although widely used, this method displays some limitations, in particular the need for large amounts of starting material. Driven by the need to quantify isotope-dilution standards used for absolute quantitative proteomics, particularly stable isotope-labeled (SIL) peptides and PSAQ proteins, we developed a new AAA assay (AAA-MS). This method requires neither derivatization nor chromatographic separation of amino acids. It is based on rapid microwave-assisted acidic hydrolysis followed by high-resolution mass spectrometry analysis of amino acids. Quantification is performed by comparing MS signals from labeled amino acids (SIL peptide- and PSAQ-derived) with those of unlabeled amino acids originating from co-hydrolyzed NIST standard reference materials. For both SIL peptides and PSAQ standards, AAA-MS quantification results were consistent with classical AAA measurements. Compared to AAA assay, AAA-MS was much faster and was 100-fold more sensitive for peptide and protein quantification. Finally, thanks to the development of a labeled protein standard, we also extended AAA-MS analysis to the quantification of unlabeled proteins.

Association of statin prescription with small abdominal aortic aneurysm progression

PubMed Central

Ferguson, Craig D.; Clancy, Paula; Bourke, Bernard; Walker, Philip J.; Dear, Anthony; Buckenham, Tim; Norman, Paul; Golledge, Jonathan

2009-01-01

Background Statins have been suggested to reduce expansion of abdominal aortic aneurysms (AAA) independent of lipid lowering effects. Methods We assessed the association of statin treatment and serum low density lipoprotein (LDL) concentrations with small AAA expansion. 652 patients undergoing surveillance of small AAAs were entered into the study from five vascular centers. In a subset fasting lipids (n=451) and other biomarkers (n=216) were measured. AAA diameter was followed by ultrasound surveillance for a median of 5 years. Results 349 (54%) of the patients were prescribed statins. Adjusting for other risk factors statin prescription was not associated with AAA growth (odds ratio, OR, 1.23, 95% confidence interval, CI, 0.86–1.76). Above median AAA growth was positively associated with initial diameter (OR 1.78 per 4.35mm larger initial aortic diameter, 95% CI 1.49–2.14) and negatively associated with diabetes (OR 0.37, 95% CI 0.22–0.62). Above median serum LDL concentration was not associated with AAA growth. Patients receiving statins had lower serum C-reactive protein concentrations but similar matrix metalloproteinase-9 and interleukin-6 concentrations to those not prescribed these medications. Conclusions We found no association between statin prescription or LDL concentration with AAA expansion. The results do not support the findings of smaller studies and suggest that statins may have no benefit in reducing AAA progression. PMID:20152231

The Antiaircraft Journal. Volume 95, Number 2, March-April 1952

DTIC Science & Technology

1952-04-01

Command, Yoko- hama. Breuning, E. G., Far East Command, Yoko- hama Cacchiotti, Ralph R., 31st AAA Brig., Ft Lewis, Wash. Colbert , Edward F., 197th AAA Gp...Wilbur B., 47th AAA Brig., Cp Stew- art, Ga. Frick, Edwin J., 336th AAA Gun Bn, Cp Ed- wards. Mass. Gildon, Milo E., USA Alaska, Fort Richard- son

A conserved inter-domain communication mechanism regulates the ATPase activity of the AAA-protein Drg1.

PubMed

Prattes, Michael; Loibl, Mathias; Zisser, Gertrude; Luschnig, Daniel; Kappel, Lisa; Rössler, Ingrid; Grassegger, Manuela; Hromic, Altijana; Krieger, Elmar; Gruber, Karl; Pertschy, Brigitte; Bergler, Helmut

2017-03-17

AAA-ATPases fulfil essential roles in different cellular pathways and often act in form of hexameric complexes. Interaction with pathway-specific substrate and adaptor proteins recruits them to their targets and modulates their catalytic activity. This substrate dependent regulation of ATP hydrolysis in the AAA-domains is mediated by a non-catalytic N-terminal domain. The exact mechanisms that transmit the signal from the N-domain and coordinate the individual AAA-domains in the hexameric complex are still the topic of intensive research. Here, we present the characterization of a novel mutant variant of the eukaryotic AAA-ATPase Drg1 that shows dysregulation of ATPase activity and altered interaction with Rlp24, its substrate in ribosome biogenesis. This defective regulation is the consequence of amino acid exchanges at the interface between the regulatory N-domain and the adjacent D1 AAA-domain. The effects caused by these mutations strongly resemble those of pathological mutations of the AAA-ATPase p97 which cause the hereditary proteinopathy IBMPFD (inclusion body myopathy associated with Paget's disease of the bone and frontotemporal dementia). Our results therefore suggest well conserved mechanisms of regulation between structurally, but not functionally related members of the AAA-family.

Homocysteine Level and Risk of Abdominal Aortic Aneurysm: A Meta-Analysis

PubMed Central

Cao, Hui; Hu, Xinhua; Zhang, Qiang; Li, Jun; Wang, Junpeng; Shao, Yang; Liu, Bing; Xin, Shijie

2014-01-01

Objectives Previous studies have reported inconsistent findings regarding the association between elevated plasma homocysteine (Hcy) levels and abdominal aortic aneurysm (AAA). We investigated this association between Hcy levels in patients with AAA and unaffected controls by conducting a meta-analysis and systematic review. Methods We conducted a systematic literature search (up to August 2013) of the PubMed database and Embase. We selected observational studies that evaluated Hcy levels in subjects with AAA compared to unaffected controls. Criteria for inclusion were the assessment of baseline Hcy and risk of AAA as an outcome. The results were presented as odd ratio (OR) and corresponding 95% confidence intervals (CI) comparing AAA patients to the control subjects. Results 7 studies with 6,445 participants were identified and analyzed. Overall, elevated plasma Hcy was associated with an increased risk of AAA (3.29; 95% CI 1.66–6.51). The pooled adjusted OR from a random effect model of only men participants in the AAA compared with the control group was 2.36 (95% CI 0.63–8.82). Conclusion This meta-analysis and systematic review suggested that Hcy significantly increased the risk of AAA. PMID:24465733

Wall Shear Stress, Wall Pressure and Near Wall Velocity Field Relationships in a Whirling Annular Seal

NASA Technical Reports Server (NTRS)

Morrison, Gerald L.; Winslow, Robert B.; Thames, H. Davis, III

1996-01-01

The mean and phase averaged pressure and wall shear stress distributions were measured on the stator wall of a 50% eccentric annular seal which was whirling in a circular orbit at the same speed as the shaft rotation. The shear stresses were measured using flush mounted hot-film probes. Four different operating conditions were considered consisting of Reynolds numbers of 12,000 and 24,000 and Taylor numbers of 3,300 and 6,600. At each of the operating conditions the axial distribution (from Z/L = -0.2 to 1.2) of the mean pressure, shear stress magnitude, and shear stress direction on the stator wall were measured. Also measured were the phase averaged pressure and shear stress. These data were combined to calculate the force distributions along the seal length. Integration of the force distributions result in the net forces and moments generated by the pressure and shear stresses. The flow field inside the seal operating at a Reynolds number of 24,000 and a Taylor number of 6,600 has been measured using a 3-D laser Doppler anemometer system. Phase averaged wall pressure and wall shear stress are presented along with phase averaged mean velocity and turbulence kinetic energy distributions located 0.16c from the stator wall where c is the seal clearance. The relationships between the velocity, turbulence, wall pressure and wall shear stress are very complex and do not follow simple bulk flow predictions.

An AAA-DDD triply hydrogen-bonded complex easily accessible for supramolecular polymers.

PubMed

Han, Yi-Fei; Chen, Wen-Qiang; Wang, Hong-Bo; Yuan, Ying-Xue; Wu, Na-Na; Song, Xiang-Zhi; Yang, Lan

2014-12-15

For a complementary hydrogen-bonded complex, when every hydrogen-bond acceptor is on one side and every hydrogen-bond donor is on the other, all secondary interactions are attractive and the complex is highly stable. AAA-DDD (A=acceptor, D=donor) is considered to be the most stable among triply hydrogen-bonded sequences. The easily synthesized and further derivatized AAA-DDD system is very desirable for hydrogen-bonded functional materials. In this case, AAA and DDD, starting from 4-methoxybenzaldehyde, were synthesized with the Hantzsch pyridine synthesis and Friedländer annulation reaction. The association constant determined by fluorescence titration in chloroform at room temperature is 2.09×10(7)  M(-1) . The AAA and DDD components are not coplanar, but form a V shape in the solid state. Supramolecular polymers based on AAA-DDD triply hydrogen bonded have also been developed. This work may make AAA-DDD triply hydrogen-bonded sequences easily accessible for stimuli-responsive materials. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Phytotoxicity and uptake of roxarsone by wheat (Triticum aestivum L.) seedlings.

PubMed

Fu, Qing-Long; Blaney, Lee; Zhou, Dong-Mei

2016-12-01

Roxarsone (ROX), the primary aromatic arsenical additive (AAA) used in animal feeding operations, is of increasing concern to environmental and human health due to land application of ROX-laden animal manure. Few studies have investigated the phytotoxicity, uptake mechanisms, and speciation of AAA in crop plants. In this study, wheat seedlings were employed to address these issues under hydroponic conditions. Compared to inorganic arsenic, ROX was less toxic to wheat root elongation. Wheat roots were more sensitive to ROX stress than shoots. For the first time, metabolized inorganic arsenic was detected in plants, although ROX was the predominant detected arsenic species in wheat seedlings. ROX uptake and toxicity to roots were inhibited by humic acid at concentrations higher than 50 mg/L due to interaction with ROX. Phosphate enhanced ROX uptake, but no trends were observed for ROX uptake in the presence of glycerol at concentrations lower than 250 mM. In addition, ROX uptake was significantly decreased by silicate (Si(IV), 0.5-10 mM) and the metabolic inhibitor, 2,4-dinitrophenol (0.5-2 mM), indicating that ROX transport into wheat roots was actively mediated by Si(IV)-sensitive transporters. These findings provide important insights into the fate and speciation of AAA in soil-water-plant systems relevant to human health. Copyright © 2016 Elsevier Ltd. All rights reserved.

Creation of Abdominal Aortic Aneurysms in Sheep by Extrapolation of Rodent Models: Is It Feasible?

PubMed

Verbrugghe, Peter; Verhoeven, Jelle; Clijsters, Marnick; Vervoort, Dominique; Coudyzer, Walter; Verbeken, Eric; Meuris, Bart; Herijgers, Paul

2018-06-07

Abdominal aortic aneurysms (AAAs) are a potentially deathly disease, needing surgical or endovascular treatment. To evaluate potentially new diagnostic tools and treatments, a large animal model, which resembles not only the morphological characteristics but also the pathophysiological background, would be useful. Rodent animal aneurysm models were extrapolated to sheep. Four groups were created: intraluminal infusion with an elastase-collagenase solution (n = 4), infusion with elastase-collagenase solution combined with proximal stenosis (n = 7), aortic xenograft (n = 3), and elastase-collagenase-treated xenograft (n = 4). At fixed time intervals (6, 12, and 24 weeks), computer tomography and autopsy with histological evaluation were performed. The described models had a high perioperative mortality (45%), due to acute aortic thrombosis or fatale hemorrhage. A maximum aortic diameter increase of 30% was obtained in the protease-stenosis group. In the protease-treated groups, some histological features of human AAAs, such as inflammation, thinning of the media, and loss of elastin could be reproduced. In the xenotransplant groups, a pronounced inflammatory reaction was visible at the start. In all models, inflammation decreased and fibrosis occurred at long follow-up, 24 weeks postoperatively. None of the extrapolated small animal aneurysm models could produce an AAA in sheep with similar morphological features as the human disease. Some histological findings of human surgical specimens could be reproduced in the elastase-collagenase-treated groups. Long-term histological evaluation indicated stabilization and healing of the aortic wall months after the initial stimulus. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

LMIP/AAA: Local Authentication, Authorization and Accounting (AAA) Protocol for Mobile IP

NASA Astrophysics Data System (ADS)

Chenait, Manel

Mobile IP represents a simple and scalable global mobility solution. However, it inhibits various vulnerabilities to malicious attacks and, therefore, requires the integration of appropriate security services. In this paper, we discuss two authentication schemes suggested for Mobile IP: standard authentication and Mobile IP/AAA authentication. In order to provide Mobile IP roaming services including identity verication, we propose an improvement to Mobile/AAA authentication scheme by applying a local politic key management in each domain, hence we reduce hando latency by avoiding the involvement of AAA infrastructure during mobile node roaming.

Sex differences in abdominal aortic aneurysms.

PubMed

Boese, Austin C; Chang, Lin; Yin, Ke-Jie; Chen, Y Eugene; Lee, Jean-Pyo; Hamblin, Milton H

2018-06-01

Abdominal aortic aneurysm (AAA) is a vascular disorder with a high case fatality rate in the instance of rupture. AAA is a multifactorial disease, and the etiology is still not fully understood. AAA is more likely to occur in men, but women have a greater risk of rupture and worse prognosis. Women are reportedly protected against AAA possibly by premenopausal levels of estrogen and are, on average, diagnosed at older ages than men. Here, we review the present body of research on AAA pathophysiology in humans, animal models, and cultured cells, with an emphasis on sex differences and sex steroid hormone signaling.

Endoplasmic reticulum-derived reactive oxygen species (ROS) is involved in toxicity of cell wall stress to Candida albicans.

PubMed

Yu, Qilin; Zhang, Bing; Li, Jianrong; Zhang, Biao; Wang, Honggang; Li, Mingchun

2016-10-01

The cell wall is an important cell structure in both fungi and bacteria, and hence becomes a common antimicrobial target. The cell wall-perturbing agents disrupt synthesis and function of cell wall components, leading to cell wall stress and consequent cell death. However, little is known about the detailed mechanisms by which cell wall stress renders fungal cell death. In this study, we found that ROS scavengers drastically attenuated the antifungal effect of cell wall-perturbing agents to the model fungal pathogen Candida albicans, and these agents caused remarkable ROS accumulation and activation of oxidative stress response (OSR) in this fungus. Interestingly, cell wall stress did not cause mitochondrial dysfunction and elevation of mitochondrial superoxide levels. Furthermore, the iron chelator 2,2'-bipyridyl (BIP) and the hydroxyl radical scavengers could not attenuate cell wall stress-caused growth inhibition and ROS accumulation. However, cell wall stress up-regulated expression of unfold protein response (UPR) genes, enhanced protein secretion and promoted protein folding-related oxidation of Ero1, an important source of ROS production. These results indicated that oxidation of Ero1 in the endoplasmic reticulum (ER), rather than mitochondrial electron transport and Fenton reaction, contributed to cell wall stress-related ROS accumulation and consequent growth inhibition. Our findings uncover a novel link between cell wall integrity (CWI), ER function and ROS production in fungal cells, and shed novel light on development of strategies promoting the antifungal efficacy of cell wall-perturbing agents against fungal infections. Copyright © 2016 Elsevier Inc. All rights reserved.

Cell Wall Metabolism in Response to Abiotic Stress

PubMed Central

Gall, Hyacinthe Le; Philippe, Florian; Domon, Jean-Marc; Gillet, Françoise; Pelloux, Jérôme; Rayon, Catherine

2015-01-01

This review focuses on the responses of the plant cell wall to several abiotic stresses including drought, flooding, heat, cold, salt, heavy metals, light, and air pollutants. The effects of stress on cell wall metabolism are discussed at the physiological (morphogenic), transcriptomic, proteomic and biochemical levels. The analysis of a large set of data shows that the plant response is highly complex. The overall effects of most abiotic stress are often dependent on the plant species, the genotype, the age of the plant, the timing of the stress application, and the intensity of this stress. This shows the difficulty of identifying a common pattern of stress response in cell wall architecture that could enable adaptation and/or resistance to abiotic stress. However, in most cases, two main mechanisms can be highlighted: (i) an increased level in xyloglucan endotransglucosylase/hydrolase (XTH) and expansin proteins, associated with an increase in the degree of rhamnogalacturonan I branching that maintains cell wall plasticity and (ii) an increased cell wall thickening by reinforcement of the secondary wall with hemicellulose and lignin deposition. Taken together, these results show the need to undertake large-scale analyses, using multidisciplinary approaches, to unravel the consequences of stress on the cell wall. This will help identify the key components that could be targeted to improve biomass production under stress conditions. PMID:27135320

DOE Office of Scientific and Technical Information (OSTI.GOV)

Badkul, R; Nicolai, W; Pokhrel, D

Purpose: To compare the impact of Pencil Beam(PB) and Anisotropic Analytic Algorithm(AAA) dose calculation algorithms on OARs and planning target volume (PTV) in thoracic spine stereotactic body radiation therapy (SBRT). Methods: Ten Spine SBRT patients were planned on Brainlab iPlan system using hybrid plan consisting of 1–2 non-coplanar conformal-dynamic arcs and few IMRT beams treated on NovalisTx with 6MV photon. Dose prescription varied from 20Gy to 30Gy in 5 fractions depending on the situation of the patient. PB plans were retrospectively recalculated using the Varian Eclipse with AAA algorithm using same MUs, MLC pattern and grid size(3mm).Differences in dose volumemore » parameters for PTV, spinal cord, lung, and esophagus were analyzed and compared for PB and AAA algorithms. OAR constrains were followed per RTOG-0631. Results: Since patients were treated using PB calculation, we compared all the AAA DVH values with respect to PB plan values as standard, although AAA predicts the dose more accurately than PB. PTV(min), PTV(Max), PTV(mean), PTV(D99%), PTV(D90%) were overestimated with AAA calculation on average by 3.5%, 1.84%, 0.95%, 3.98% and 1.55% respectively as compared to PB. All lung DVH parameters were underestimated with AAA algorithm mean deviation of lung V20, V10, V5, and 1000cc were 42.81%,19.83%, 18.79%, and 18.35% respectively. AAA overestimated Cord(0.35cc) by mean of 17.3%; cord (0.03cc) by 12.19% and cord(max) by 10.5% as compared to PB. Esophagus max dose were overestimated by 4.4% and 5cc by 3.26% for AAA algorithm as compared to PB. Conclusion: AAA overestimated the PTV dose values by up to 4%.The lung DVH had the greatest underestimation of dose by AAA versus PB. Spinal cord dose was overestimated by AAA versus PB. Given the critical importance of accuracy of OAR and PTV dose calculation for SBRT spine, more accurate algorithms and validation of calculated doses in phantom models are indicated.« less

Wall shear stress measurement in blade end-wall corner region

NASA Technical Reports Server (NTRS)

Bhargava, R.; Raj, R.; Boldman, D. R.

1987-01-01

The magnitude and the direction of wall shear stress and surface pressure in the blade end-wall corner region were investigated. The measurements were obtained on a specially designed Preston tube, the tip of which could be concentrically rotated about its axis of rotation at the measurement location. The magnitude of wall shear stress in the vicinity of the corner was observed to increase significantly (170 percent) compared to its far-upstream value; the increase was consistently higher on the blade surface compared to the value on the plate surface of the blade end-wall corner. On both surfaces in the blade end-wall corner, the variation of the wall shear stress direction was found to be more predominant in the vicinity of the blade leading-edge location. The trend of the measured wall shear stress direction showed good agreement with the limiting streamline directions obtained from the flow visualization studies.

Mutant Analysis Reveals Allosteric Regulation of ClpB Disaggregase

PubMed Central

Franke, Kamila B.; Bukau, Bernd; Mogk, Axel

2017-01-01

The members of the hexameric AAA+ disaggregase of E. coli and S. cerevisiae, ClpB, and Hsp104, cooperate with the Hsp70 chaperone system in the solubilization of aggregated proteins. Aggregate solubilization relies on a substrate threading activity of ClpB/Hsp104 fueled by ATP hydrolysis in both ATPase rings (AAA-1, AAA-2). ClpB/Hsp104 ATPase activity is controlled by the M-domains, which associate to the AAA-1 ring to downregulate ATP hydrolysis. Keeping M-domains displaced from the AAA-1 ring by association with Hsp70 increases ATPase activity due to enhanced communication between protomers. This communication involves conserved arginine fingers. The control of ClpB/Hsp104 activity is crucial, as hyperactive mutants with permanently dissociated M-domains exhibit cellular toxicity. Here, we analyzed AAA-1 inter-ring communication in relation to the M-domain mediated ATPase regulation, by subjecting a conserved residue of the AAA-1 domain subunit interface of ClpB (A328) to mutational analysis. While all A328X mutants have reduced disaggregation activities, their ATPase activities strongly differed. ClpB-A328I/L mutants have reduced ATPase activity and when combined with the hyperactive ClpB-K476C M-domain mutation, suppress cellular toxicity. This underlines that ClpB ATPase activation by M-domain dissociation relies on increased subunit communication. The ClpB-A328V mutant in contrast has very high ATPase activity and exhibits cellular toxicity on its own, qualifying it as novel hyperactive ClpB mutant. ClpB-A328V hyperactivity is however, different from that of M-domain mutants as M-domains stay associated with the AAA-1 ring. The high ATPase activity of ClpB-A328V primarily relies on the AAA-2 ring and correlates with distinct conformational changes in the AAA-2 catalytic site. These findings characterize the subunit interface residue A328 as crucial regulatory element to control ATP hydrolysis in both AAA rings. PMID:28275610

Prevalence of previously undiagnosed abdominal aortic aneurysms in the area of Como: the ComoCuore "looking for AAA" ultrasonography screening.

PubMed

Corrado, Giovanni; Durante, Alessandro; Genchi, Vincenzo; Trabattoni, Loris; Beretta, Sandro; Rovelli, Enza; Foglia-Manzillo, Giovanni; Ferrari, Giovanni

2016-08-01

The prognosis for abdominal aortic aneurysm (AAA) rupture is poor. Long-term follow-up of population-based randomized trials has demonstrated that ultrasound (US) screening for abdominal aortic aneurysms (AAAs) measuring 3 cm or greater decreases AAA-related mortality rates and is cost-effective. We though to prospectively perform during a 26-month period a limited US examination of the infrarenal aorta in volunteers of both gender aged 60-85 years without history of AAA living in the area of Como, Italy. From September 2010 to November 2013 ComoCuore, a no-profit nongovernmental association, enrolled 1555 people (aged 68.8 ± 6.8 years; 48.6 % males). Clinical data and a US imaging of the aorta were collected for each participant. AAA was found in 22 volunteers (1.4 %) mainly males (2.5 % in males vs. 0.4 % in females p = 0.005). Overall, the prevalence of cardiovascular risk factors was higher in patients with vs. without AAA (mean 2.9 ± 3.0 vs. 1.4 ± 1.0 respectively, p < 0.0001). Independent predictors of AAA on multivariate analysis were age (OR 1.14, 1.06-1.22; p < 0.0001), male gender (OR 8.23, 1.79-37.91; p = 0.007), and both current (OR 4.98, 1.57-15.79; p = 0.007) and previous smoking (OR 2.76, 1.12-8.94; p = 0.03). Our study confirms the feasibility of one time US screening for AAA in a large cohort of asymptomatic people. Independent predictors of AAA were male sex, older age and a history of smoking. Accordingly to recent data the prevalence of AAA seems to be declining, maybe due to a reduction of smoking in Italy.

Molecular cloning and expression of five glutathione S-transferase (GST) genes from Banana (Musa acuminata L. AAA group, cv. Cavendish).

PubMed

Wang, Zhuo; Huang, Suzhen; Jia, Caihong; Liu, Juhua; Zhang, Jianbin; Xu, Biyu; Jin, Zhiqiang

2013-09-01

Three tau class MaGSTs responded to abiotic stress, MaGSTF1 and MaGSTL1 responded to signaling molecules, they may play an important role in the growth of banana plantlet. Glutathione S-transferases (GST) are multifunctional detoxification enzymes that participate in a variety of cellular processes, including stress responses. In this study, we report the molecular characteristics of five GST genes (MaGSTU1, MaGSTU2, MaGSTU3, MaGSTF1 and MaGSTL1) cloned from banana (Musa acuminate L. AAA group, cv. Cavendish) using a RACE-PCR-based strategy. The predicted molecular masses of these GSTs range from 23.4 to 27.7 kDa and their pIs are acidic. At the amino acid level, they share high sequence similarity with GSTs in the banana DH-Pahang (AA group) genome. Phylogenetic analysis showed that the deduced amino acid sequences of MaGSTs also have high similarity to GSTs of other plant species. Expression analysis by semi-quantitative RT-PCR revealed that these genes are differentially expressed in various tissues. In addition, their expression is regulated by various stress conditions, including exposure to signaling molecules, cold, salinity, drought and Fusarium oxysporum f specialis(f. Sp) cubense Tropical Race 4 (Foc TR4) infection. The expression of the tau class MaGSTs (MaGSTU1, MaGSTU2 and MaGSTU3) mainly responded to cold, salinity and drought while MaGSTF1 and MaGSTL1 expressions were upregulated by signaling molecules. Our findings suggest that MaGSTs play a key role in both development and abiotic stress responses.

Attenuation of aortic aneurysms with stem cells from different genders.

PubMed

Davis, John P; Salmon, Morgan; Pope, Nicolas H; Lu, Guanyi; Su, Gang; Sharma, Ashish K; Ailawadi, Gorav; Upchurch, Gilbert R

2015-11-01

No medical therapies are yet available to slow abdominal aortic aneurysm (AAA) growth. This study sought to investigate the effect of different genders of bone marrow-derived mesenchymal stem cells (MSC) on AAA growth in a murine AAA model. Given the decreased rate of AAA in women, it is hypothesized that female MSC would attenuate AAA growth more so than male MSC. Aortas of 8-10-wk-old male C57Bl/6 mice were perfused with purified porcine pancreatic elastase to induce AAA formation. Bone marrow-derived MSC from male and female mice were dosed via tail vein injection (3 million cells per dose, 500 μL of volume per injection) on postaortic perfusion days 1, 3, and 5. Aortas were harvested after 14 d. Mean aortic dilation in the elastase group was 121 ± 5.2% (mean ± standard error of the mean), while male MSC inhibited AAA growth (87.8 ± 6.9%, P = 0.008) compared with that of elastase. Female MSC showed the most marked attenuation of AAA growth (75.2 ± 8.3% P = 0.0004). Proinflammatory cytokines tumor necrosis factor α, interleukin 1β, and monocyte chemotactic protein-1 (MCP-1) were only decreased in tissues treated with female MSC (P = 0.017, P = 0.001, and P < 0.0001, respectively, when compared with elastase). These data exhibit that female MSC more strongly attenuate AAA growth in the murine model. Furthermore, female MSC and male MSC inhibit proinflammatory cytokines at varying levels. The effects of MSC on aortic tissue offer a promising insight into biologic therapies for future medical treatment of AAAs in humans. Copyright © 2015 Elsevier Inc. All rights reserved.

The prevalence of abdominal aortic aneurysms in the rural/urban population in central Poland - Gniewkowo Aortic Study.

PubMed

Dereziński, Tadeusz L; Fórmankiewicz, Bartosz; Migdalski, Arkadiusz; Brazis, Paweł; Jakubowski, Grzegorz; Woda, Łukasz; Jawień, Arkadiusz

2017-01-01

Abdominal aortic aneurysm (AAA) is a widening of the aorta below the renal arteries with a diameter equal to or greater than 3 cm. The prevalence of AAA is estimated at 4-8% in men aged 65 years or older and 1-2% among women over 65 years old. Participation in screening programmes has decreased the number of aortic ruptures. All men aged 60 years and older, and women aged 65 years and older living in the rural/urban commune in central Poland were invited to participate in the study. In total 922 persons (61% of the invited population) entered the study. The men were divided into two groups: 60-64 years old, and 65 years and older. Screening abdomen ultrasound was performed and demographic data was collected. Among the 922 examined persons two (1.01%) AAAs were diagnosed in the group of men 60-64 years of age, three (0.82%) AAAs amongst women ≥ 65 years old, and 33 (9.29%) AAAs were found in the group of men aged 65 years and older. A positive relationship between the presence of AAA and smoking (p = 0.0048), age of men (p = 0.0009), and history of myocardial infarction/acute coronary syndrome (MI/ACS) (p = 0.0079) was found. There was no correlation between the frequency of AAA and diabetes mellitus (p = 0.46), hypertension (p = 0.38), and family history of AAA (p = 0.44). The prevalence of AAA in men aged 65 years and older is seemingly larger than in previously conducted studies, while among men 60-64 years of age and women aged ≥ 65 it is similar. Older age, smoking, and a history of MI/ACS were the most important risk factors of AAA occurrence.

Clinical Efficacy of Transthoracic Echocardiography for Screening Abdominal Aortic Aneurysm in Turkish Patients.

PubMed

Kilic, Salih; Saracoglu, Erhan; Cekici, Yusuf

2018-03-01

The objective of this study was to investigate the prevalence of abdominal aortic aneurysm (AAA) in Turkish patients aged ≥ 65 years, and to demonstrate the applicability of echocardiography to AAA screening. Transthoracic echocardiography (TTE) was performed in all consecutive patients aged ≥ 65 years who were referred to cardiology clinics or were referred from other outpatient clinics. The abdominal aorta (AA) of each patient was scanned using the same probe, and the time spent was recorded. Demographic and clinic characteristics of the patients were recorded at the end of the echocardiography. Among 1948 patients (mean age 70.9 ± 6 years; 49.8% male), the AA was visualized in 96.3%. AAA was identified in 3.7% (69/1878) of the patients, of whom AAA was previously known in 20.3% (n = 14). The prevalence of unknown AAA was 2.93%. The average time needed to scan and measure the AA was 1 minute and 3 seconds (±23 seconds). Aortic root diameters were significantly higher in the patients with AAA than in those without AAA (34.7 ± 4.2 vs. 29.8 ± 4.7; p < 0.001). Age (per 1 year increase) [odds ratio (OR), 1.245; p < 0.001], male gender (OR, 5.382; p < 0.001), smoking (OR, 2.118; p = 0.037), and aortic root diameter (per 1 mm increase) (OR, 1.299; p < 0.001) were independent predictors of AAA. This study is important in that it showed a high prevalence of AAA in Turkish patients aged ≥ 65 years, and demonstrated that AAA can be visualized in the majority of patients in as little as 1 minute during TTE.

Identification of a genetic variant associated with abdominal aortic aneurysms on chromosome 3p12.3 by genome wide association.

PubMed

Elmore, James R; Obmann, Melissa A; Kuivaniemi, Helena; Tromp, Gerard; Gerhard, Glenn S; Franklin, David P; Boddy, Amy M; Carey, David J

2009-06-01

The goal of this project was to identify genetic variants associated with abdominal aortic aneurysms (AAAs). A genome wide association study was carried out using pooled DNA samples from 123 AAA cases and 112 controls matched for age, gender, and smoking history using Affymetrix 500K single nucleotide polymorphism (SNP) arrays (Affymetrix, Inc, Santa Clara, Calif). The difference in mean allele frequency between cases and controls was calculated for each SNP and used to identify candidate genomic regions. Association of candidate SNPs with AAA was confirmed by individual TaqMan genotype assays in a total of 2096 cases and controls that included an independent replication sample set. A genome wide association study of AAA cases and controls identified a candidate AAA-associated haplotype on chromosome 3p12.3. By individual genotype analysis, four SNPs in this region were significantly associated with AAA in cases and controls from the original study population. One SNP in this region (rs7635818) was genotyped in a total of 502 cases and 736 controls from the original study population (P = .017) and 448 cases and 410 controls from an independent replication sample (P = .013; combined P value = .0028; combined odds ratio [OR] = 1.33). An even stronger association with AAA was observed in a subset of smokers (391 cases, 241 controls, P = .00041, OR = 1.80), which represent the highest risk group for AAA. The AAA-associated haplotype is located approximately 200 kbp upstream of the CNTN3 gene transcription start site. This study identifies a region on chromosome 3 that is significantly associated with AAA in 2 distinct study populations.

Geometric analysis of ruptured and nonruptured abdominal aortic aneurysms.

PubMed

Kimura, Masaru; Hoshina, Katsuyuki; Miyahara, Kazuhiro; Nitta, Jun; Kobayashi, Masaharu; Yamamoto, Sota; Ohshima, Marie

2018-06-15

The objective of this study was to use parameters to determine the geometric differences between ruptured abdominal aortic aneurysms (AAAs) and nonruptured AAAs. Computed tomography data of 38 ruptured AAAs and 215 electively repaired (nonruptured) AAAs were collected from multiple institutes. We compared the ruptured AAA group and nonruptured AAA group with 1:1 matching by using the Mahalanobis distance, which was calculated using the patient's age, sex, and AAA diameter. We selected the longitudinal AAA image in multiplanar reconstruction view, placed a hypothetical ellipse on the aneurysm's protruded curve, and placed a circle on the portion connecting the aneurysm and the aorta. We then measured the aspect ratio (the vertical diameter divided by the horizontal diameter) and fillet radius (the radius of arc). The aspect ratio was significantly lower in the ruptured group than in the nonruptured group (2.02 ± 0.53 vs 2.60 ± 1.02; P = .002), as was the fillet radius (0.28 ± 0.18 vs 0.81 ± 0.44; P < .001). Receiver operating characteristic analysis revealed that the area under the curve of the aspect ratio was 0.688, and the optimal cutoff point was 2.23, with sensitivity and specificity of 0.55 and 0.76, respectively. The area under the curve of the fillet radius was 0.933, and the optimal cutoff was 0.347, with sensitivity and specificity of 0.97 and 0.87, respectively. The geometric analysis performed in this study revealed that ruptured AAAs had a smaller fillet radius and smaller aspect ratio than nonruptured AAAs did. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Plasma D-dimer as a predictor of the progression of abdominal aortic aneurysm.

PubMed

Vele, E; Kurtcehajic, A; Zerem, E; Maskovic, J; Alibegovic, E; Hujdurovic, A

2016-11-01

Essentials D-dimer could provide important information about abdominal aortic aneurysm (AAA) progression. The greatest diameter of the infrarenal aorta and the value of plasma D-dimer were determined. AAA progression is correlated with increasing plasma D-dimer levels. The increasing value of plasma D-dimer could be a predictor of aneurysm progression. Background The natural course of abdominal aortic aneurysm (AAA) is mostly asymptomatic and unpredictable. D-dimer could provide potentially important information about subsequent AAA progression. Objectives The aims of this study were to establish the relationship between the progression of an abdominal aortic aneurysm (AAA) and plasma D-dimer concentration over a 12-month period and determine the value of plasma D-dimer in patients with sub-aneurysmal aortic dilatation. Patients/Methods This was a prospective observational study that involved 33 patients with an AAA, 30 patients with sub-aneurysmal aortic dilatation and 30 control subjects. The greatest diameter of the infrarenal aorta, which was assessed by ultrasound, and the value of plasma D-dimer were determined for all subjects at baseline assessment, as well as after 12 months for those with an AAA. Results A positive correlation was found between the diameter of an AAA and plasma D-dimer concentration at the baseline and the control measurement stages. There was a strong positive correlation between AAA progression and increasing plasma D-dimer concentration over a 12-month period. Among patients with sub-aneurysmal aortic dilatation (n = 30), the value of plasma D-dimer was higher compared with matched controls (n = 30). Conclusions There is a strongly positive correlation between AAA progression and increasing plasma D-dimer concentration. The value of plasma D-dimer is higher in patients with sub-aneurysmal aortic dilatation than in control subjects. © 2016 International Society on Thrombosis and Haemostasis.

Variation in Death Rate After Abdominal Aortic Aneurysmectomy in the United States

PubMed Central

Dimick, Justin B.; Stanley, James C.; Axelrod, David A.; Kazmers, Andris; Henke, Peter K.; Jacobs, Lloyd A.; Wakefield, Thomas W.; Greenfield, Lazar J.; Upchurch, Gilbert R.

2002-01-01

Objective To determine whether high-volume hospitals (HVHs) have lower in-hospital death rates after abdominal aortic aneurysm (AAA) repair compared with low-volume hospitals (LVHs). Summary Background Data Select statewide studies have shown that HVHs have superior outcomes compared with LVHs for AAA repair, but they may not be representative of the true volume–outcome relationship for the entire United States. Methods Patients undergoing repair of intact or ruptured AAAs in the Nationwide Inpatient Sample (NIS) for 1996 and 1997 were included (n = 13,887) for study. The NIS represents a 20% stratified random sample representative of all U.S. hospitals. Unadjusted and case mix-adjusted analyses were performed. Results The overall death rate was 3.8% for intact AAA repair and 47% for ruptured AAA repair. For repair of intact AAAs, HVHs had a lower death rate than LVHs. The death rate after repair of ruptured AAA was also slightly lower at HVHs. In a multivariate analysis adjusting for case mix, having surgery at an LVH was associated with a 56% increased risk of in-hospital death. Other independent risk factors for in-hospital death included female gender, age older than 65 years, aneurysm rupture, urgent or emergent admission, and comorbid disease. Conclusions This study from a representative national database documents that HVHs have a significantly lower death rate than LVHs for repair of both intact and ruptured AAA. These data support the regionalization of patients to HVHs for AAA repair. PMID:11923615

Comparison of Conscious Sedation and Asleep-Awake-Asleep Techniques for Awake Craniotomy.

PubMed

Dilmen, Ozlem Korkmaz; Akcil, Eren Fatma; Oguz, Abdulvahap; Vehid, Hayriye; Tunali, Yusuf

2017-01-01

Since awake craniotomy (AC) has become a standard of care for supratentorial tumour resection, especially in the motor and language cortex, determining the most appropriate anaesthetic protocol is very important. The aim of this retrospective study is to compare the effectiveness of conscious sedation (CS) to "awake-asleep-awake" (AAA) techniques for supratentorial tumour resection. Forty-two patients undergoing CS and 22 patients undergoing AAA were included in the study. The primary endpoint was to compare the CS and AAA techniques with respect to intraoperative pain and agitation in patients undergoing supratentorial tumour resection. The secondary endpoint was comparison of the other intraoperative complications. This study results show that the incidence of intraoperative agitation and seizure were lower in the AAA group than in the CS group. Intraoperative blood pressures were significantly higher in the CS group than in the AAA group during the pinning and incision, but the level of blood pressures did not need antihypertensive treatment. Otherwise, blood pressures were significantly higher in the AAA group than in the CS group during the neurological examination and the severity of hypertension needed statistically significant more antihypertensive treatment in the AAA group. As a result of hypertension, the amount of intraoperative bleeding was higher in the AAA group than in the CS group. In conclusion, the AAA technique may provide better results with respect to agitation and seizure, but intraoperative hypertension needed a vigilant follow-up especially in the wake-up period. Copyright © 2016 Elsevier Ltd. All rights reserved.

Statins: the holy grail of Abdominal Aortic Aneurysm (AAA) growth attenuation? A systematic review of the literature.

PubMed

Dunne, Jonathan A; Bailey, Marc A; Griffin, Kathryn J; Sohrabi, Soroush; Coughlin, Patrick A; Scott, D Julian A

2014-01-01

In the era of Abdominal Aortic Aneurysm (AAA) screening, pharmacotherapies to attenuate AAA growth are sought. HMG Co-A reductase inhibitors (statins) have pleiotropic actions independent of their lipid lowering effects and have been suggested as potential treatment for small AAAs. We systematically review the clinical evidence for this effect. Medline, EMBASE and the Cochrane Central Register of Controlled Trials (1950-2011) were searched for studies reporting data on the role of statin therapy on AAA growth rate. No language restrictions were placed on the search. References of retrieved articles and pertinent journals were hand searched. Included studies were reviewed by 2 independent observers. The search retrieved 164 papers, 100 were irrelevant based on their title, 47 were reviews and 1 was a letter. 8 studies were excluded based on review of their abstract leaving 8 for inclusion in the study. Eight observational clinical studies with a total of 4,466 patients were reviewed. Four studies demonstrated reduced AAA expansion in statin users while 4 studies failed to demonstrate this effect. The method of determining AAA growth rates varied significantly between the studies and the ability of many studies to control for misclassification bias was poor. The claim that statins attenuate AAA growth remains questionable. Further prospective studies with stringent identification and verification of statin usage and a standardised method of estimating AAA growth rates are required. Statin type and dose also merit consideration.

Epidemiology and contemporary management of abdominal aortic aneurysms.

PubMed

Ullery, Brant W; Hallett, Richard L; Fleischmann, Dominik

2018-05-01

Abdominal aortic aneurysm (AAA) is most commonly defined as a maximal diameter of the abdominal aorta in excess of 3 cm in either anterior-posterior or transverse planes or, alternatively, as a focal dilation ≥ 1.5 times the diameter of the normal adjacent arterial segment. Risk factors for the development of AAA include age > 60, tobacco use, male gender, Caucasian race, and family history of AAA. Aneurysm growth and rupture risk appear to be associated with persistent tobacco use, female gender, and chronic pulmonary disease. The majority of AAAs are asymptomatic and detected incidentally on various imaging studies, including abdominal ultrasound, and computed tomographic angiography. Symptoms associated with AAA may include abdominal or back pain, thromboembolization, atheroembolization, aortic rupture, or development of an arteriovenous or aortoenteric fistula. The Screening Abdominal Aortic Aneurysms Efficiently (SAAAVE) Act provides coverage for a one-time screening abdominal ultrasound at age 65 for men who have smoked at least 100 cigarettes and women who have family history of AAA disease. Medical management is recommended for asymptomatic patients with AAAs < 5 cm in diameter and focuses on modifiable risk factors, including smoking cessation and blood pressure control. Primary indications for intervention in patients with AAA include development of symptoms, rupture, rapid aneurysm growth (> 5 mm/6 months), or presence of a fusiform aneurysm with maximum diameter of 5.5 cm or greater. Intervention for AAA includes conventional open surgical repair and endovascular aortic stent graft repair.

An investigation on near wall transport characteristics in an adiabatic upward gas-liquid two-phase slug flow

NASA Astrophysics Data System (ADS)

Zheng, Donghong; Che, Defu

2007-08-01

The near-wall transport characteristics, inclusive of mass transfer coefficient and wall shear stress, which have a great effect on gas-liquid two-phase flow induced internal corrosion of low alloy pipelines in vertical upward oil and gas mixing transport, have been both mechanistically and experimentally investigated in this paper. Based on the analyses on the hydrodynamic characteristics of an upward slug unit, the mass transfer in the near wall can be divided into four zones, Taylor bubble nose zone, falling liquid film zone, Taylor bubble wake zone and the remaining liquid slug zone; the wall shear stress can be divided into two zones, the positive wall shear stress zone associated with the falling liquid film and the negative wall shear stress zone associated with the liquid slug. Based on the conventional mass transfer and wall shear stress characteristics formulas of single phase liquid full-pipe turbulent flow, corrected normalized mass transfer coefficient formula and wall shear stress formula are proposed. The calculated results are in good agreement with the experimental data. The shear stress and the mass transfer coefficient in the near wall zone are increased with the increase of superficial gas velocity and decreased with the increase of superficial liquid velocity. The mass transfer coefficients in the falling liquid film zone and the wake zone of leading Taylor bubble are lager than those in the Taylor bubble nose zone and the remaining liquid slug zone, and the wall shear stress associated falling liquid film is larger than that associated the liquid slug. The mass transfer coefficient is within 10-3 m/s, and the wall shear stress below 103 Pa. It can be concluded that the alternate wall shear stress due to upward gas-liquid slug flow is considered to be the major cause of the corrosion production film fatigue cracking.

Microbubbles and Blood Brain Barrier Opening: A Numerical Study on Acoustic Emissions and Wall Stress Predictions

PubMed Central

Goertz, David E.; Hynynen, Kullervo

2015-01-01

Focused ultrasound with microbubbles is an emerging technique for blood brain barrier (BBB) opening. Here, a comprehensive theoretical model of a bubble-fluid-vessel system has been developed which accounts for the bubble’s non-spherical oscillations inside a microvessel, and its resulting acoustic emissions. Numerical simulations of unbound and confined encapsulated bubbles were performed to evaluate the effect of the vessel wall on acoustic emissions and vessel wall stresses. Using a Marmottant shell model, the normalized second harmonic to fundamental emissions first decreased as a function of pressure (>50 kPa) until reaching a minima ("transition point") at which point they increased. The transition point of unbound compared to confined bubble populations occurred at different pressures and was associated with an accompanying increase in shear and circumferential wall stresses. As the wall stresses depend on the bubble to vessel wall distance, the stresses were evaluated for bubbles with their wall at a constant distance to a flat wall. As a result, the wall stresses were bubble size and frequency dependent and the peak stress values induced by bubbles larger than resonance remained constant versus frequency at a constant mechanical index. PMID:25546853

Protein quality control in organelles - AAA/FtsH story.

PubMed

Janska, Hanna; Kwasniak, Malgorzata; Szczepanowska, Joanna

2013-02-01

This review focuses on organellar AAA/FtsH proteases, whose proteolytic and chaperone-like activity is a crucial component of the protein quality control systems of mitochondrial and chloroplast membranes. We compare the AAA/FtsH proteases from yeast, mammals and plants. The nature of the complexes formed by AAA/FtsH proteases and the current view on their involvement in degradation of non-native organellar proteins or assembly of membrane complexes are discussed. Additional functions of AAA proteases not directly connected with protein quality control found in yeast and mammals but not yet in plants are also described shortly. Following an overview of the molecular functions of the AAA/FtsH proteases we discuss physiological consequences of their inactivation in yeast, mammals and plants. The molecular basis of phenotypes associated with inactivation of the AAA/FtsH proteases is not fully understood yet, with the notable exception of those observed in m-AAA protease-deficient yeast cells, which are caused by impaired maturation of mitochondrial ribosomal protein. Finally, examples of cytosolic events affecting protein quality control in mitochondria and chloroplasts are given. This article is part of a Special Issue entitled: Protein Import and Quality Control in Mitochondria and Plastids. Copyright © 2012 Elsevier B.V. All rights reserved.

Abdominal aortic aneurysm: novel mechanisms and therapies.

PubMed

Davis, Frank M; Rateri, Debra L; Daugherty, Alan

2015-11-01

Abdominal aortic aneurysm (AAA) is a pathological condition of permanent dilation that portends the potentially fatal consequence of aortic rupture. This review emphasizes recent advances in mechanistic insight into aneurysm pathogenesis and potential pharmacologic therapies that are on the horizon for AAAs. An increasing body of evidence demonstrates that genetic factors, including 3p12.3, DAB2IP, LDLr, LRP1, matrix metalloproteinase (MMP)-3, TGFBR2, and SORT1 loci, are associated with AAA development. Current human studies and animal models have shown that many leukocytes and inflammatory mediators, such as IL-1, IL-17, TGF-β, and angiotensin II, are involved in the pathogenesis of AAAs. Leukocytic infiltration into aortic media leads to smooth muscle cell depletion, generation of reactive oxygen species, and extracellular matrix fragmentation. Preclinical investigations into pharmacological therapies for AAAs have provided intriguing insight into the roles of microRNAs in regulating many pathological pathways in AAA development. Several large clinical trials are ongoing, seeking to translate preclinical findings into therapeutic options. Recent studies have identified many potential mechanisms involved in AAA pathogenesis that provide insight into the development of a medical treatment for this disease.

The m-AAA Protease Associated with Neurodegeneration Limits MCU Activity in Mitochondria.

PubMed

König, Tim; Tröder, Simon E; Bakka, Kavya; Korwitz, Anne; Richter-Dennerlein, Ricarda; Lampe, Philipp A; Patron, Maria; Mühlmeister, Mareike; Guerrero-Castillo, Sergio; Brandt, Ulrich; Decker, Thorsten; Lauria, Ines; Paggio, Angela; Rizzuto, Rosario; Rugarli, Elena I; De Stefani, Diego; Langer, Thomas

2016-10-06

Mutations in subunits of mitochondrial m-AAA proteases in the inner membrane cause neurodegeneration in spinocerebellar ataxia (SCA28) and hereditary spastic paraplegia (HSP7). m-AAA proteases preserve mitochondrial proteostasis, mitochondrial morphology, and efficient OXPHOS activity, but the cause for neuronal loss in disease is unknown. We have determined the neuronal interactome of m-AAA proteases in mice and identified a complex with C2ORF47 (termed MAIP1), which counteracts cell death by regulating the assembly of the mitochondrial Ca 2+ uniporter MCU. While MAIP1 assists biogenesis of the MCU subunit EMRE, the m-AAA protease degrades non-assembled EMRE and ensures efficient assembly of gatekeeper subunits with MCU. Loss of the m-AAA protease results in accumulation of constitutively active MCU-EMRE channels lacking gatekeeper subunits in neuronal mitochondria and facilitates mitochondrial Ca 2+ overload, mitochondrial permeability transition pore opening, and neuronal death. Together, our results explain neuronal loss in m-AAA protease deficiency by deregulated mitochondrial Ca 2+ homeostasis. Copyright © 2016 Elsevier Inc. All rights reserved.

Structural Elements Regulating AAA+ Protein Quality Control Machines.

PubMed

Chang, Chiung-Wen; Lee, Sukyeong; Tsai, Francis T F

2017-01-01

Members of the ATPases Associated with various cellular Activities (AAA+) superfamily participate in essential and diverse cellular pathways in all kingdoms of life by harnessing the energy of ATP binding and hydrolysis to drive their biological functions. Although most AAA+ proteins share a ring-shaped architecture, AAA+ proteins have evolved distinct structural elements that are fine-tuned to their specific functions. A central question in the field is how ATP binding and hydrolysis are coupled to substrate translocation through the central channel of ring-forming AAA+ proteins. In this mini-review, we will discuss structural elements present in AAA+ proteins involved in protein quality control, drawing similarities to their known role in substrate interaction by AAA+ proteins involved in DNA translocation. Elements to be discussed include the pore loop-1, the Inter-Subunit Signaling (ISS) motif, and the Pre-Sensor I insert (PS-I) motif. Lastly, we will summarize our current understanding on the inter-relationship of those structural elements and propose a model how ATP binding and hydrolysis might be coupled to polypeptide translocation in protein quality control machines.

Benefits and harms of screening men for abdominal aortic aneurysm in Sweden: a registry-based cohort study.

PubMed

Johansson, Minna; Zahl, Per Henrik; Siersma, Volkert; Jørgensen, Karsten Juhl; Marklund, Bertil; Brodersen, John

2018-06-16

Large reductions in the incidence of abdominal aortic aneurysm (AAA) and AAA-related mortality mean that results from randomised trials of screening for the disorder might be out-dated. The aim of this study was to estimate the effect of AAA screening in Sweden on disease-specific mortality, incidence, and surgery. Individual data on the incidence of AAA, AAA mortality, and surgery for AAA in a cohort of men aged 65 years who were invited to screening between 2006 and 2009, were compared with data from an age-matched contemporaneous cohort of men who were not invited for AAA screening. We also analysed national data for all men aged 40-99 years between Jan 1, 1987, and Dec 31, 2015, to explore background trends. Adjustment for confounding was done by weighting the analyses with a propensity score obtained from a logistic regression model on cohort year, marital status, educational level, income, and whether the patient already had an AAA diagnosis at baseline. Adjustment for differential attrition was also done by weighting the analyses with the inverse probability of still being in the cohort 6 years after screening. Generalised estimating equations were used to adjust the variance for repeated measurement and in response to the weighting. AAA mortality in Swedish men has decreased from 36 to ten deaths per 100 000 men aged 65-74 years between the early 2000s and 2015. Mortality decreased at similar rates in all Swedish counties, irrespective of whether AAA screening was offered. After 6 years with screening, we found a non-significant reduction in AAA mortality associated with screening (adjusted odds ratio [aOR] 0·76, 95% CI 0·38-1·51), which means that two men (95% CI -3 to 7) avoid death from AAA for every 10 000 men offered screening. Screening was associated with increased odds of AAA diagnosis (aOR 1·52, 95% CI 1·16-1·99; p=0·002) and an increased risk of elective surgery (aOR 1·59, 95% CI 1·20-2·10; p=0·001), such that for every 10 000 men offered screening, 49 men (95% CI 25-73) were likely to be overdiagnosed, 19 of whom (95% CI 1-37) had avoidable surgery that increased their risk of mortality and morbidity. AAA screening in Sweden did not contribute substantially to the large observed reductions in AAA mortality. The reductions were mostly caused by other factors, probably reduced smoking. The small benefit and substantially less favourable benefit-to-harm balance call the continued justification of the intervention into question. Research Unit and Section for General Practice, FoUU-centrum Fyrbodal, Sweden, and the region of Västra Götaland, Sweden. Copyright © 2018 Elsevier Ltd. All rights reserved.

On investigating wall shear stress in two-dimensional plane turbulent wall jets

NASA Astrophysics Data System (ADS)

Mehdi, Faraz; Johansson, Gunnar; White, Christopher; Naughton, Jonathan

2012-11-01

Mehdi & White [Exp Fluids 50:43-51(2011)] presented a full momentum integral based method for determining wall shear stress in zero pressure gradient turbulent boundary layers. They utilized the boundary conditions at the wall and at the outer edge of the boundary layer. A more generalized expression is presented here that uses just one boundary condition at the wall. The method is mathematically exact and has an advantage of having no explicit streamwise gradient terms. It is successfully applied to two different experimental plane turbulent wall jet datasets for which independent estimates of wall shear stress were known. Complications owing to experimental inaccuracies in determining wall shear stress from the proposed method are also discussed.

Low prevalence of abdominal aortic aneurysm in the Seychelles population aged 50 to 65 years.

PubMed

Yerly, Patrick; Madeleine, George; Riesen, Walter; Bovet, Pascal

2013-03-01

The prevalence of abdominal aortic aneurysm (AAA) and its risk factors are well known in Western countries but few data are available from low- and middle- income countries. We are not aware of systematically collected population- based data on AAA in the African region. We evaluated the prevalence of AAA in a population- based cardiovascular survey conducted in the Republic of Seychelles in 2004 (Indian Ocean, African region). Among the 353 participants aged 50 to 64 years and screened with ultrasound, the prevalence of AAA was 0.3% (95% CI: 0- 0.9) and the prevalence of ectatic dilatations of the abdominal aorta was 1.5% (95% CI: 0.2- 2.8). The prevalence of AAA in the general population seemed lower in Seychelles than in Western countries, despite a high prevalence in Seychelles of risk factors of AAA, such as smoking (in men), high blood pressure and hypercholesterolaemia.

Recent Advances in Molecular Mechanisms of Abdominal Aortic Aneurysm Formation

PubMed Central

Annambhotla, Suman; Bourgeois, Sebastian; Wang, Xinwen; Lin, Peter H.; Yao, Qizhi; Chen, Changyi

2010-01-01

Abdominal Aortic Aneurysm (AAA) is an increasingly common clinical condition with fatal implications. It is associated with advanced age, male gender, cigarette smoking, atherosclerosis, hypertension, and genetic predisposition. Although significant evidence has emerged in the last decade, the molecular mechanisms of AAA formation remains poorly understood. Currently, the treatment for AAA remains primarily surgical with the lone innovation of endovascular therapy. With advance in the human genome, understanding precisely which molecules and genes mediate AAA development and blocking their activity at the molecular level could lead to important new discoveries and therapies. This review summarizes recent updates in molecular mechanisms of AAA formation including animal models, autoimmune components, infection, key molecules and cytokines, mechanical forces, genetics and pharmacotherapy. This review will be helpful to those who want to recognize the newest endeavors within the field and identify possible lines of investigation in AAA. PMID:18259804

In vivo topical application of acetyl aspartic acid increases fibrillin-1 and collagen IV deposition leading to a significant improvement of skin firmness.

PubMed

Gillbro, J M; Merinville, E; Cattley, K; Al-Bader, T; Hagforsen, E; Nilsson, M; Mavon, A

2015-10-01

Acetyl aspartic acid (A-A-A) was discovered through gene array analysis with corresponding Cmap analysis. We found that A-A-A increased keratinocyte regeneration, inhibited dermal matrix metalloprotease (MMP) expression and relieved fibroblast stiffness through reduction of the fibroblast stiffness marker F-actin. Dermal absorption studies showed successful delivery to both the epidermal and dermal regions, and in-use trial demonstrated that 1% A-A-A was well tolerated. In this study, the aim was to investigate whether A-A-A could stimulate the synthesis of extracellular matrix supporting proteins in vivo and thereby improving the viscoelastic properties of human skin by conducting a dual histological and biophysical clinical study. Two separate double-blind vehicle-controlled in vivo studies were conducted using a 1% A-A-A containing oil-in-water (o/w) emulsion. In the histological study, 16 female volunteers (>55 years of age) exhibiting photodamaged skin on their forearm were included, investigating the effect of a 12-day treatment of A-A-A on collagen IV (COLIV) and fibrillin-1. In a subsequent pilot study, 0.1% retinol was used for comparison to A-A-A (1%). The biomechanical properties of the skin were assessed in a panel of 16 women (>45 years of age) using the standard Cutometer MPA580 after topical application of the test products for 28 days. The use of multiple suction enabled the assessment of F4, an area parameter specifically representing skin firmness. Twelve-day topical application of 1% A-A-A significantly increased COLIV and fibrillin with 13% and 6%, respectively, compared to vehicle. 1% A-A-A and 0.1% retinol were found to significantly reduce F4 after 28 days of treatment by 15.8% and 14.7%, respectively, in the pilot Cutometer study. No significant difference was found between retinol and A-A-A. However, only A-A-A exhibited a significant effect vs. vehicle on skin firmness which indicated the incremental benefit of A-A-A as a skin-firming active ingredient. In this study, we showed the in vivo efficacy of 1% A-A-A both on a protein level (fibrillin and collagen IV) and on a clinical end point, specifically skin firmness, providing proof that, acetyl aspartic acid has a strong potential as an anti-ageing 'cosmeceutical' ingredient answering the needs of our key consumer base. © 2015 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

The Relationship Between Serum Interleukin-1α and Asymptomatic Infrarenal Abdominal Aortic Aneurysm Size, Morphology, and Growth Rates.

PubMed

Ahmad, Mehtab; Kuravi, Sahithi; Hodson, James; Rainger, G Ed; Nash, Gerard B; Vohra, Rajiv K; Bradbury, Andrew W

2018-02-16

In a pilot study, a relationship between abdominal aortic aneurysm (AAA) diameter and serum interleukin (IL)-1α levels was reported, and that endothelial cell (EC) activation in vitro in response to serum from patients with AAA was blocked by anti-IL-1α antibodies. The aim of the present study was to further investigate the relationship between serum IL-1α and asymptomatic infrarenal AAA size, morphology, and growth rates. Serum IL-1α was measured using enzyme linked immunosorbent assay in 101 patients with asymptomatic, infrarenal AAA and related to aneurysm size, morphology, and growth rates. IL-1α was measured in 101 patients. There was no statistically significant difference in mean age between men and women. IL-1α was detectable in 62.4% of patients; median IL-1α titre was 3.26 pg/mL. There was no statistically significant relationship between IL-1α and maximum AAA antero-posterior diameter as measured by ultrasound (p = .649), AAA morphology (aortic length [p = .394], sac [p = .369], and thrombus volume [p = .629]) as measured on computed tomography, absolute increase in AAA diameter (p = .214), or AAA growth rate (p = .230). IL-1α is detectable in the majority of patients with infrarenal AAA, but the cause and clinical significance of this novel observation remains unknown. Copyright © 2018 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Abdominal aortic aneurysm screening program using hand-held ultrasound in primary healthcare

PubMed Central

Kostov, Belchin; Navarro González, Marta; Cararach Salami, Daniel; Pérez Jiménez, Alfonso; Gilabert Solé, Rosa; Bru Saumell, Concepció; Donoso Bach, Lluís; Villalta Martí, Mireia; González-de Paz, Luis; Ruiz Riera, Rafael; Riambau Alonso, Vicenç; Acar-Denizli, Nihan; Farré Almacellas, Marta; Ramos-Casals, Manuel; Benavent Àreu, Jaume

2017-01-01

We determined the feasibility of abdominal aortic aneurysm (AAA) screening program led by family physicians in public primary healthcare setting using hand-held ultrasound device. The potential study population was 11,214 men aged ≥ 60 years attended by three urban, public primary healthcare centers. Participants were recruited by randomly-selected telephone calls. Ultrasound examinations were performed by four trained family physicians with a hand-held ultrasound device (Vscan®). AAA observed were verified by confirmatory imaging using standard ultrasound or computed tomography. Cardiovascular risk factors were determined. The prevalence of AAA was computed as the sum of previously-known aneurysms, aneurysms detected by the screening program and model-based estimated undiagnosed aneurysms. We screened 1,010 men, with mean age of 71.3 (SD 6.9) years; 995 (98.5%) men had normal aortas and 15 (1.5%) had AAA on Vscan®. Eleven out of 14 AAA-cases (78.6%) had AAA on confirmatory imaging (one patient died). The total prevalence of AAA was 2.49% (95%CI 2.20 to 2.78). The median aortic diameter at diagnosis was 3.5 cm in screened patients and 4.7 cm (p<0.001) in patients in whom AAA was diagnosed incidentally. Multivariate logistic regression analysis identified coronary heart disease (OR = 4.6, 95%CI 1.3 to 15.9) as the independent factor with the highest odds ratio. A screening program led by trained family physicians using hand-held ultrasound was a feasible, safe and reliable tool for the early detection of AAA. PMID:28453577

Analysis of the cooperative ATPase cycle of the AAA+ chaperone ClpB from Thermus thermophilus by using ordered heterohexamers with an alternating subunit arrangement.

PubMed

Yamasaki, Takashi; Oohata, Yukiko; Nakamura, Toshiki; Watanabe, Yo-hei

2015-04-10

The ClpB/Hsp104 chaperone solubilizes and reactivates protein aggregates in cooperation with DnaK/Hsp70 and its cofactors. The ClpB/Hsp104 protomer has two AAA+ modules, AAA-1 and AAA-2, and forms a homohexamer. In the hexamer, these modules form a two-tiered ring in which each tier consists of homotypic AAA+ modules. By ATP binding and its hydrolysis at these AAA+ modules, ClpB/Hsp104 exerts the mechanical power required for protein disaggregation. Although ATPase cycle of this chaperone has been studied by several groups, an integrated understanding of this cycle has not been obtained because of the complexity of the mechanism and differences between species. To improve our understanding of the ATPase cycle, we prepared many ordered heterohexamers of ClpB from Thermus thermophilus, in which two subunits having different mutations were cross-linked to each other and arranged alternately and measured their nucleotide binding, ATP hydrolysis, and disaggregation abilities. The results indicated that the ATPase cycle of ClpB proceeded as follows: (i) the 12 AAA+ modules randomly bound ATP, (ii) the binding of four or more ATP to one AAA+ ring was sensed by a conserved Arg residue and converted another AAA+ ring into the ATPase-active form, and (iii) ATP hydrolysis occurred cooperatively in each ring. We also found that cooperative ATP hydrolysis in at least one ring was needed for the disaggregation activity of ClpB. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Disparities in outcomes for Hispanic patients undergoing endovascular and open abdominal aortic aneurysm repair.

PubMed

Williams, Timothy K; Schneider, Eric B; Black, James H; Lum, Ying Wei; Freischlag, Julie A; Perler, Bruce A; Abularrage, Christopher J

2013-01-01

Previous studies have demonstrated racial and ethnic disparities associated with the outcomes of abdominal aortic aneurysm (AAA) repair, although little is known about the influence of race and ethnicity on the costs associated with these disparities. The current study was undertaken to examine the influence of race and ethnicity on the outcomes of endovascular (EVAR) and open repair (open AAA) of unruptured AAA and its effect on costs in contemporary practice. The Nationwide Inpatient Sample (2005 to 2008) was queried using ICD-9-CM codes for unruptured AAA (441.4). The primary outcomes were mortality and total hospital charges. Multivariate analyses were performed adjusting for age, gender, race, comorbidities (Charlson index), year, insurance type, and hospital characteristics. A total of 62,728 patients underwent EVAR and 24,253 patients underwent open AAA. White patients (72%) were more likely to undergo EVAR than Hispanic (69%) or black patients (69%; P = 0.02). On univariate analysis, in-hospital mortality after EVAR was increased in Hispanic patients compared with white patients (1% vs 2%; P = 0.02). There were no differences in mortality after EVAR between white and black patients, and there were no racial or ethnic differences in mortality after open AAA. Hispanic ethnicity remained an independent risk factor for increased mortality after AAA repair on multivariate analysis (RR 1.64; 95% CI [1.05 to 2.57]; P = 0.03). Hispanic ethnicity was associated with increased hospital charges compared with white ethnicity after both EVAR ($108,886 vs $77,748; P < 0.001) and open AAA ($134,356 vs $85,536; P < 0.001) and for black patients after open AAA ($101,168 vs $85,536; P = 0.04). Hispanic ethnicity is an independent risk factor for mortality after AAA repair independent of insurance type or hospital characteristics. There were dramatic disparities in hospital costs for Hispanic patients undergoing either EVAR or open AAA and for black patients after open AAA compared with white patients. This observation seems unrelated to length of stay, postoperative complications, and admission status. Further studies are needed to determine whether these disparities extend beyond the primary hospitalization. Copyright © 2013 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.

Safety assessment of a novel active ingredient, acetyl aspartic acid, according to the EU Cosmetics Regulation and the Scientific Committee on Consumer Safety guidelines.

PubMed

Daly, P; Moran, G

2015-10-01

Acetyl aspartic acid (A-A-A) was proposed as a new novel active ingredient for use in cosmetics. The safety of A-A-A was assessed by following an in-house-developed 'New Ingredient Testing Strategy', which was designed in accordance with the Scientific Committee on Consumer Safety (SCCS) notes of guidance and the requirements of Annex I of the EU Cosmetics Regulation. The aim of the project was to determine whether A-A-A was safe for use in cosmetics and to determine a maximum permitted safe level in the formulations. A literature review was conducted, consulting over 40 different information sources. This highlighted a number of gaps which required testing data. A-A-A was tested for phototoxicity according to OECD test guideline 432, skin irritation according to OECD test guideline 439 and eye irritation according to OECD test guideline 437. Dermal absorption of A-A-A was measured according to OECD test guideline 428 and was used to calculate the margin of safety (MoS). Finally, A-A-A was tested in a human repeat insult patch test (HRIPT) and a 14-day in-use tolerance study. A-A-A was non-phototoxic and was non-irritating to skin and eyes in in vitro testing. Dermal absorption was calculated to be 5%. The MoS for A-A-A was 351, at a level of 5%, for all cosmetic product types, indicating no systemic safety toxicity concern. A-A-A at 5% under occlusive patch on a panel of 50 adult volunteers induced no skin irritation or allergic reaction in the HRIPT study. Finally, repeated application of A-A-A to the periocular area, twice per day for 14 days, in 21 female volunteers, demonstrated that 1% A-A-A was well tolerated following dermatological and ophthalmological assessment in a cosmetic formulation. A-A-A was assessed as safe by the cosmetic safety assessor for use in cosmetics at a level of 5% in all cosmetic product types, in line with the requirements of the EU Cosmetics Regulation and in accordance with the SCCS notes of guidance. © 2015 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Wall relaxation and the driving forces for cell expansive growth

NASA Technical Reports Server (NTRS)

Cosgrove, D. J.

1987-01-01

When water uptake by growing cells is prevented, the turgor pressure and the tensile stress in the cell wall are reduced by continued wall loosening. This process, termed in vivo stress relaxation, provides a new way to study the dynamics of wall loosening and to measure the wall yield threshold and the physiological wall extensibility. Stress relaxation experiments indicate that wall stress supplies the mechanical driving force for wall yielding. Cell expansion also requires water absorption. The driving force for water uptake during growth is created by wall relaxation, which lowers the water potential of the expanding cells. New techniques for measuring this driving force show that it is smaller than believed previously; in elongating stems it is only 0.3 to 0.5 bar. This means that the hydraulic resistance of the water transport pathway is small and that rate of cell expansion is controlled primarily by wall loosening and yielding.

Inflammatory Cells and Proteases in Abdominal Aortic Aneurysm and its Complications.

PubMed

Haiying, Jiang; Sasaki, Takeshi; Jin, Enze; Kuzuya, Masafumi; Cheng, Xianwu

2018-05-30

Abdominal aortic aneurysm (AAA), a common disease among elderly individuals, involves the progressive dilatation of the abdominal aorta as a consequence of degeneration. The mechanisms of AAA formation, development and rupture are largely unknown. Surgical repair is the only available method of treatment since the lack of knowledge regarding the pathogenesis of AAA has hindered the development of suitable medical treatments, particularly the development of drugs. In this review, we describe the inflammatory cells and proteases that may be involved in the formation and development of AAA. This knowledge can contribute to the development of new drugs for AAA. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Fundamental Characteristics of AAA+ Protein Family Structure and Function.

PubMed

Miller, Justin M; Enemark, Eric J

2016-01-01

Many complex cellular events depend on multiprotein complexes known as molecular machines to efficiently couple the energy derived from adenosine triphosphate hydrolysis to the generation of mechanical force. Members of the AAA+ ATPase superfamily (ATPases Associated with various cellular Activities) are critical components of many molecular machines. AAA+ proteins are defined by conserved modules that precisely position the active site elements of two adjacent subunits to catalyze ATP hydrolysis. In many cases, AAA+ proteins form a ring structure that translocates a polymeric substrate through the central channel using specialized loops that project into the central channel. We discuss the major features of AAA+ protein structure and function with an emphasis on pivotal aspects elucidated with archaeal proteins.

Intraoperative CT in the assessment of posterior wall acetabular fracture stability.

PubMed

Cunningham, Brian; Jackson, Kelly; Ortega, Gil

2014-04-01

Posterior wall acetabular fractures that involve 10% to 40% of the posterior wall may or may not require an open reduction and internal fixation. Dynamic stress examination of the acetabular fracture under fluoroscopy has been used as an intraoperative method to assess joint stability. The aim of this study was to demonstrate the value of intraoperative ISO computed tomography (CT) examination using the Siemens ISO-C imaging system (Siemens Corp, Malvern, Pennsylvania) in the assessment of posterior wall acetabular fracture stability during stress examination under anesthesia. In 5 posterior wall acetabular fractures, standard fluoroscopic images (including anteroposterior pelvis and Judet radiographs) with dynamic stress examinations were compared with the ISO-C CT imaging system to assess posterior wall fracture stability during stress examination. After review of standard intraoperative fluoroscopic images under dynamic stress examination, all 5 cases appeared to demonstrate posterior wall stability; however, when the intraoperative images from the ISO-C CT imaging system demonstrated that 1 case showed fracture instability of the posterior wall segment during stress examination, open reduction and internal fixation was performed. The use of intraoperative ISO CT imaging has shown an initial improvement in the surgeon's ability to assess the intraoperative stability of posterior wall acetabular fractures during stress examination when compared with standard fluoroscopic images. Copyright 2014, SLACK Incorporated.

Associations of Diabetes and Obesity with Risk of Abdominal Aortic Aneurysm in Men.

PubMed

Wang, Lu; Djousse, Luc; Song, Yiqing; Akinkuolie, Akintunde O; Matsumoto, Chisa; Manson, JoAnn E; Gaziano, J Michael; Sesso, Howard D

2017-01-01

Background. The associations of diabetes and obesity with the risk of abdominal aortic aneurysm (AAA) are inconclusive in previous studies. Subjects/Methods. We conducted prospective analysis in the Physicians' Health Study. Among 25,554 male physicians aged ≥ 50 years who reported no AAA at baseline, 471 reported a newly diagnosed AAA during a mean of 10.4 years' follow-up. Results. Compared with men who had baseline body mass index (BMI) < 25 kg/m 2 , the multivariable hazard ratio (HR [95% CI]) of newly diagnosed AAA was 1.30 [1.06-1.59] for BMI 25-<30 kg/m 2 and 1.69 [1.24-2.30] for BMI ≥ 30 kg/m 2 . The risk of diagnosed AAA was significantly higher by 6% with each unit increase in baseline BMI. This association was consistent regardless of the other known AAA risk factors and preexisting vascular diseases. Overall, baseline history of diabetes tended to be associated with a lower risk of diagnosed AAA (HR = 0.79 [0.57-1.11]); this association appeared to vary by follow-up time (HR = 1.56 and 0.63 during ≤ and >2 years' follow-up, resp.). Conclusion. In a large cohort of middle-aged and older men, obesity was associated with a higher risk, while history of diabetes tended to associate with a lower risk of diagnosed AAA, particularly over longer follow-up.

Effect of AMPK signal pathway on pathogenesis of abdominal aortic aneurysms

PubMed Central

Yang, Le; Shen, Lin; Gao, Peixian; Li, Gang; He, Yuxiang; Wang, Maohua; Zhou, Hua; Yuan, Hai; Jin, Xing; Wu, Xuejun

2017-01-01

Background and aims Determine the effect of AMPK activation and inhibition on the development of AAA (abdominal aortic aneurysm). Methods AAA was induced in ApoE−/− mice by Ang II (Angiotensin II)-infusion. AICAR (5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside) was used as AMPK activator and Compound C was used as AMPK inhibitor. We further investigate the effect of metformin, a widely used anti-diabetic drug which could activate AMPK signal pathway, on the pathogenesis of aneurysm. Results Phospho-AMPK level was significantly decreased in AAA tissue compared with control aortas. AICAR significantly reduced the incidence, severity and mortality of aneurysm in the Ang II-infusion model. AICAR also alleviated macrophage infiltration and neovascularity in Ang II infusion model at day 28. The expression of pro-inflammatory factors, angiogenic factors and the activity of MMPs were also alleviated by AICAR during AAA induction. On the other hand, Compound C treatment did not exert obvious protective effect. AMPK activation may inhibit the activation of nuclear factor-κB (NF-κB) and signal transducer and activator of transcription-3 (STAT-3) during AAA induction. Administration of metformin also activated AMPK signal pathway and retarded AAA progression in Ang II infusion model. Conclusions Activation of AMPK signaling pathway may inhibit the Ang II-induced AAA in mice. Metformin may be a promising approach to the treatment of AAA. PMID:29190959

Assessment of the accuracy of AortaScan for detection of abdominal aortic aneurysm (AAA).

PubMed

Abbas, A; Smith, A; Cecelja, M; Waltham, M

2012-02-01

AortaScan AMI 9700 is a portable 3D ultrasound device that automatically measures the maximum diameter of the abdominal aorta without the need for a trained sonographer. It is designed to rapidly diagnose or exclude an AAA and may have particular use in screening programs. Our objective was to determine its accuracy to detect AAA. Subjects from our AAA screening and surveillance programs were examined. The aorta was scanned using the AortaScan and computed tomography (CT). Ninety-one subjects underwent imaging (44 AAA on conventional ultrasound surveillance and 47 controls). The largest measurement obtained by AortaScan was compared against the CT-aortic measurement. The mean aortic diameter was 2.8 cm. The CT scan confirmed the diagnosis of AAA in 43 subjects. There was one false positive measurement on conventional ultrasound. AortaScan missed the diagnosis of AAA in eight subjects. There were thirteen false positive measurements. The sensitivity, specificity, positive and negative predictive values were 81%, 72%, 72% and 81% respectively. A device to detect AAA without the need for a trained operator would have potential in a community-based screening programme. The AortaScan, however, lacks adequate sensitivity and significant technical improvement is necessary before it could be considered a replacement for trained screening personnel. Copyright © 2011 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

KRE5 Suppression Induces Cell Wall Stress and Alternative ER Stress Response Required for Maintaining Cell Wall Integrity in Candida glabrata

PubMed Central

Sasaki, Masato; Ito, Fumie; Aoyama, Toshio; Sato-Okamoto, Michiyo; Takahashi-Nakaguchi, Azusa; Chibana, Hiroji; Shibata, Nobuyuki

2016-01-01

The maintenance of cell wall integrity in fungi is required for normal cell growth, division, hyphae formation, and antifungal tolerance. We observed that endoplasmic reticulum stress regulated cell wall integrity in Candida glabrata, which possesses uniquely evolved mechanisms for unfolded protein response mechanisms. Tetracycline-mediated suppression of KRE5, which encodes a predicted UDP-glucose:glycoprotein glucosyltransferase localized in the endoplasmic reticulum, significantly increased cell wall chitin content and decreased cell wall β-1,6-glucan content. KRE5 repression induced endoplasmic reticulum stress-related gene expression and MAP kinase pathway activation, including Slt2p and Hog1p phosphorylation, through the cell wall integrity signaling pathway. Moreover, the calcineurin pathway negatively regulated cell wall integrity, but not the reduction of β-1,6-glucan content. These results indicate that KRE5 is required for maintaining both endoplasmic reticulum homeostasis and cell wall integrity, and that the calcineurin pathway acts as a regulator of chitin-glucan balance in the cell wall and as an alternative mediator of endoplasmic reticulum stress in C. glabrata. PMID:27548283

Abdominal Aortic Aneurysms in “High-Risk” Surgical Patients

PubMed Central

Jordan, William D.; Alcocer, Francisco; Wirthlin, Douglas J.; Westfall, Andrew O.; Whitley, David

2003-01-01

Objective To evaluate the early results of endovascular grafting for high-risk surgical candidates in the treatment of abdominal aortic aneurysms (AAA). Summary Background Data Since the approval of endoluminal grafts for treatment of AAA, endovascular repair of AAA (EVAR) has expanded to include patients originally considered too ill for open AAA repair. However, some concern has been expressed regarding technical failure and the durability of endovascular grafts. Methods The University of Alabama at Birmingham (UAB) Computerized Vascular Registry identified all patients who underwent abdominal aneurysm repair between January 1, 2000, and June 12, 2002. Patients were stratified by type of repair (open AAA vs. EVAR) and were classified as low risk or high risk. Patients with at least one of the following classifications were classified as high risk: age more than 80 years, chronic renal failure (creatinine > 2.0), compromised cardiac function (diminished ventricular function or severe coronary artery disease), poor pulmonary function, reoperative aortic procedure, a “hostile” abdomen, or an emergency operation. Death, systemic complications, and length of stay were tabulated for each group. Results During this 28-month period, 404 patients underwent AAA repair at UAB. Eighteen patients (4.5%) died within 30 days of their repair or during the same hospitalization. Two hundred seventeen patients (53%) were classified as high risk. Two hundred fifty-nine patients (64%) underwent EVAR repair, and 130 (50%) of these were considered high-risk patients (including four emergency procedures). One hundred forty-five patients (36%) underwent open AAA repair, including 15 emergency operations. All deaths occurred in the high-risk group: 12 (8.3%) died after open AAA repair and 6 (2.3%) died after EVAR repair. Postoperative length of stay was shorter for EVAR repair compared to open AAA. Conclusions High-risk and low-risk patients can undergo EVAR repair with a lower rate of short-term systemic complications and a shorter length of stay compared to open AAA. Despite concern regarding the durability of EVAR, high-risk patients should be evaluated for EVAR repair before committing to open AAA repair. PMID:12724628

SU-F-T-609: Impact of Dosimetric Variation for Prescription Dose Using Analytical Anisotropic Algorithm (AAA) in Lung SBRT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kawai, D; Takahashi, R; Kamima, T

Purpose: Actual irradiated prescription dose to patients cannot be verified. Thus, independent dose verification and second treatment planning system are used as the secondary check. AAA dose calculation engine has contributed to lung SBRT. We conducted a multi-institutional study to assess variation of prescription dose for lung SBRT when using AAA in reference to using Acuros XB and Clarkson algorithm. Methods: Six institutes in Japan participated in this study. All SBRT treatments were planed using AAA in Eclipse and Adaptive Convolve (AC) in Pinnacle3. All of the institutes used a same independent dose verification software program (Simple MU Analysis: SMU,more » Triangle Product, Ishikawa, Japan), which implemented a Clarkson-based dose calculation algorithm using CT image dataset. A retrospective analysis for lung SBRT plans (73 patients) was performed to compute the confidence limit (CL, Average±2SD) in dose between the AAA and the SMU. In one of the institutes, a additional analysis was conducted to evaluate the variations between the AAA and the Acuros XB (AXB). Results: The CL for SMU shows larger systematic and random errors of 8.7±9.9 % for AAA than the errors of 5.7±4.2 % for AC. The variations of AAA correlated with the mean CT values in the voxels of PTV (a correlation coefficient : −0.7) . The comparison of AXB vs. AAA shows smaller systematic and random errors of −0.7±1.7%. The correlation between dose variations for AXB and the mean CT values in PTV was weak (0.4). However, there were several plans with more than 2% deviation of AAPM TG114 (Maximum: −3.3 %). Conclusion: In comparison for AC, prescription dose calculated by AAA may be more variable in lung SBRT patient. Even AXB comparison shows unexpected variation. Care should be taken for the use of AAA in lung SBRT. This research is partially supported by Japan Agency for Medical Research and Development (AMED)« less

A knowledge-based design framework for airplane conceptual and preliminary design

NASA Astrophysics Data System (ADS)

Anemaat, Wilhelmus A. J.

The goal of work described herein is to develop the second generation of Advanced Aircraft Analysis (AAA) into an object-oriented structure which can be used in different environments. One such environment is the third generation of AAA with its own user interface, the other environment with the same AAA methods (i.e. the knowledge) is the AAA-AML program. AAA-AML automates the initial airplane design process using current AAA methods in combination with AMRaven methodologies for dependency tracking and knowledge management, using the TechnoSoft Adaptive Modeling Language (AML). This will lead to the following benefits: (1) Reduced design time: computer aided design methods can reduce design and development time and replace tedious hand calculations. (2) Better product through improved design: more alternative designs can be evaluated in the same time span, which can lead to improved quality. (3) Reduced design cost: due to less training and less calculation errors substantial savings in design time and related cost can be obtained. (4) Improved Efficiency: the design engineer can avoid technically correct but irrelevant calculations on incomplete or out of sync information, particularly if the process enables robust geometry earlier. Although numerous advancements in knowledge based design have been developed for detailed design, currently no such integrated knowledge based conceptual and preliminary airplane design system exists. The third generation AAA methods are tested over a ten year period on many different airplane designs. Using AAA methods will demonstrate significant time savings. The AAA-AML system will be exercised and tested using 27 existing airplanes ranging from single engine propeller, business jets, airliners, UAV's to fighters. Data for the varied sizing methods will be compared with AAA results, to validate these methods. One new design, a Light Sport Aircraft (LSA), will be developed as an exercise to use the tool for designing a new airplane. Using these tools will show an improvement in efficiency over using separate programs due to the automatic recalculation with any change of input data. The direct visual feedback of 3D geometry in the AAA-AML, will lead to quicker resolving of problems as opposed to conventional methods.

Prospective Observational Evaluation of Time-Dependency of Adalimumab Immunogenicity and Drug Concentrations: The Poetic Study.

PubMed

Ungar, Bella; Engel, Tal; Yablecovitch, Doron; Lahat, Adi; Lang, Alon; Avidan, Benjamin; Har-Noy, Ofir; Carter, Dan; Levhar, Nina; Selinger, Limor; Neuman, Sandra; Natour, Ola Haj; Yavzori, Miri; Fudim, Ella; Picard, Orit; Kopylov, Uri; Chowers, Yehuda; Naftali, Timna; Broide, Efrat; Shachar, Eyal; Eliakim, Rami; Ben-Horin, Shomron

2018-06-01

Adalimumab is usually self-injected at home, making prospective serial-sampling studies challenging and scarce. This has led to a gap in knowledge about evolution of anti-adalimumab antibodies (AAAs) over time and its correlation with clinical and inflammatory outcomes. A program for home visits by physicians at induction, every 3 months and at event of relapse, was established prospectively for Crohn's disease (CD) patients. At each visit, patients' clinical scores were determined and sera were obtained for C-reactive protein, drug, and AAA levels. This cohort was compared to a parallel prospective cohort of infliximab-treated CD patients. In a subgroup of 29 patients, trough and in-between-trough levels were compared, to elucidate the importance of timing of sampling during the injection cycle. Ninety-eight CD patients starting adalimumab were prospectively followed (median follow-up 44 weeks) and 621 serum samples were analyzed. Thirty-three patients (32%) developed AAA; 18/33 (55%) of them as early as week 2, and 26/33 (79%) by week 14. Induction period AAAs were strongly associated with primary non-response (odds ratio (OR) = 5.4, 95% confidence interval (CI): 1.6-17.8, p = 0.005). As compared to antibodies-to-infliximab (ATI), AAA formation rate over time was significantly lower (p = 0.01) and AAA were much more specific-85% of AAA events were associated with loss-of-response compared with 58% rate for ATI (p = 0.01). In 29 patients sampled serially during an injection cycle, levels of drug and AAA seemed comparable between four time-points during a single cycle both in patients with or without AAA (n = 8, n = 21, respectively). When followed prospectively and serially, AAAs are found to arise earlier than previously appreciated and their impact may be more pronounced for primary rather than secondary, non-response. Drug and AAA levels were similar both at trough and in-between injections, enabling to simplify therapeutic drug monitoring of adalimumab.

Polymorphisms of the interleukin-6 gene promoter and abdominal aortic aneurysm.

PubMed

Smallwood, L; Allcock, R; van Bockxmeer, F; Warrington, N; Palmer, L J; Iacopetta, B; Norman, P E

2008-01-01

Elevated levels of circulating interleukin-6 (IL-6) have been reported in patients with abdominal aortic aneurysms (AAAs). Although this implicates inflammation as a cause of AAAs, there is also evidence that the aneurysmal aorta may secrete IL-6 into the circulation as a result of aortic proteolysis. Genetic association studies are one means of trying to clarify the role of specific mediators in the causal pathway. The aim of the present study was to examine the association between variants of the IL-6 gene and AAAs. An association study involving 677 men with screen-detected AAAs and 656 age-matched controls was performed. Three variants in the IL-6 promoter region were analysed: IL-6-174G>C (rs1800795), IL-6-572G>C (rs1800796) and IL-6-597G>A (rs1800797). Univariate regression of SNP genotype on AAA as a binary outcome was initially performed under a range of genetic models (additive, dominant and recessive). This was followed by multivariate analyses, testing the same models but including risk factors known to be associated with AAAs. All analyses and haplotype estimation were performed under a generalized linear model framework. IL-6-572G>C polymorphism (frequency 1.5% in cases) was identified as an independent risk factor for AAA with an odds ratio (OR) of 6.00 (95%CI: 1.22, 29.41) when applied to the recessive model. No association was seen in the additive or dominant models. In a multivariate analysis using the most common haplotype (h.111, frequency 48.7%) as a reference, h.211 (frequency 4.4%) was an independent risk factor for AAA (OR 1.56, 95%CI: 1.02, 2.39). The IL-6 572G>C polymorphism (and h.211 haplotype) is associated with AAA, however it is too rare to be an important cause of most AAAs. This does not support the concept that the elevated level of IL-6 reported in patients with AAAs is a primary cause of the aneurysmal process.

Adalimumab for Treatment of Noninfectious Uveitis: Immunogenicity and Clinical Relevance of Measuring Serum Drug Levels and Antidrug Antibodies.

PubMed

Cordero-Coma, Miguel; Calleja-Antolín, Sara; Garzo-García, Irene; Nuñez-Garnés, Ana M; Álvarez-Castro, Carolina; Franco-Benito, Manuel; Ruiz de Morales, Jose G

2016-12-01

To evaluate the rate of immunogenicity induced by adalimumab and its relationship with drug serum levels and clinical responses in patients with noninfectious uveitis. Prospective observational study. Consecutive patients from 1 referral center who initiated treatment with adalimumab for active noninfectious uveitis resistant to conventional therapy. All patients received 40 mg adalimumab every other week. Patients were evaluated clinically and immunologically before and after 4, 8, and 24 weeks of treatment. Clinical evaluation included assessment of changes in visual acuity, degree of inflammation in the anterior chamber and vitreous cavity, central macular thickness, and retinal angiographic leakage. Immunologic evaluation included assessment of serum trough adalimumab and antibodies against adalimumab (AAA) levels and class II HLA typing. Twenty-five patients were enrolled. Overall, 18 of 25 patients (72%) showed a favorable clinical response to adalimumab therapy. Eleven patients (44%) achieved a complete response and 7 (28%) achieved a partial response. However, 7 of 25 patients (28%) were considered nonresponders. Median trough adalimumab serum levels were higher in responders than in nonresponders (P < 0.001). We observed AAA positivity (AAA+) at least 1 time point in 8 of 25 patients (32%), including 4 with transitory AAA and 4 with permanent AAA. In all patients with permanent AAA+, trough adalimumab levels became undetectable (P < 0.001). However, in patients who demonstrated transitory AAA+, no correlation was observed between AAA titers and adalimumab trough levels (P = 0.2).Concomitant immunosuppression did not show any protective effect on adalimumab immunogenicity in our cohort. An association between the presence of AAA+ and a worse uveitis outcome was observed only in patients with permanent AAA+, which correlated with undetectable adalimumab trough levels (P = 0.014). Treatment of noninfectious uveitis with adalimumab is associated with high rates of favorable clinical response. Overall, adalimumab trough levels were higher in responder patients. Development of permanent AAA was associated with undetectable trough adalimumab levels and worse uveitis outcome. Immunogenicity was more common in patients in whom uveitis was associated with a systemic disease and was not influenced by concomitant immunosuppressors. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Carotid and coronary disease management prior to open and endovascular aortic surgery. What are the current guidelines?

PubMed

Thompson, J P

2014-04-01

Several bodies produce broadly concurring and updated guidelines for the evaluation and treatment of cardiovascular disease in both surgical and non-surgical patients. Recent developments include revised recommendations on preoperative stress testing, referral for possible coronary revascularization and medical management. It is recognized that non-invasive cardiac tests are relatively poor at predicting perioperative risk, and "prophylactic" coronary revascularization has a limited role. The planned aortic intervention (open or endovascular repair) also influences preoperative management. Patients presenting for elective abdominal aortic aneurysm (AAA) repair should only be referred for cardiological testing if they have active symptoms of coronary artery disease (CAD), known CAD and poor functional exercise capacity, or multiple risk factors for CAD. Coronary revascularization before AAA surgery should be limited to patients with established indications, so cardiac stress testing should only be performed if it would change management i.e. the patient is a candidate for and would benefit from coronary revascularization. When endovascular aortic repair is planned, it is reasonable to proceed to surgery without further cardiac stress testing or evaluation unless otherwise indicated. All non-emergency patients require medical optimization, but perioperative beta blockade benefits only certain patients. Some of the data informing recent guidelines have been questioned and some guidelines are being revised. Current guidelines do not specifically address the management of patients with known or suspected carotid artery disease who may require aortic surgery. For these patients, an individualized approach is required. This review considers recent guidelines. Algorithms for investigation and management based on their recommendations are included.

Oxidative stress reduces trophoblast FOXO1 and integrin β3 expression that inhibits cell motility.

PubMed

Chen, Chie-Pein; Chen, Cheng-Yi; Wu, Yi-Hsin; Chen, Chia-Yu

2018-06-08

Preeclampsia is a serious pregnancy complication associated with placental oxidative stress and impaired trophoblast migration. The mechanism of defective trophoblast migration remains unknown. Forkhead box O1 (FOXO1) is a transcription factor. Integrin β3 is involved in cell motility. We hypothesized that FOXO1 mediates expression of trophoblast integrin β3, which could be impaired by oxidative stress and have implications in preeclampsia. The expressions of FOXO1 and integrin β3 were significantly reduced in preeclamptic placentas (n = 15) compared to that of controls (n = 15; p < 0.01). HTR-8/SVneo and JEG-3 trophoblasts were transfected to express wild-type FOXO1-WT or constitutively-expressed nuclear mutant form, FOXO1-AAA. The FOXO1 in HTR-8/SVneo and 3A-Sub-E trophoblasts was silenced by small interfering RNA. AKT-mediated phosphorylation inactivated FOXO1, but FOXO1-AAA was not phosphorylated. The expression of trophoblast integrin β3 was significantly elevated by FOXO1 overexpression and inhibited by FOXO1 knockdown. FOXO1 regulates integrin β3 at the transcriptional level via binding to the putative FOXO1 response element site between position -1154 to -1139 (TGAGATGTTTTGAAAG) in HTR-8/SVneo trophoblasts. The level of phosphorylated FOXO1 was decreased, and the FOXO1 level was increased in trophoblasts treated with AKT inhibitor MK2206, leading to upregulation of integrin β3. The capabilities of trophoblast adhesion and migration were enhanced by FOXO1-overexpression or MK2206, and inhibited by silencing FOXO1 or oxidative stress with H 2 O 2 . These results suggest that FOXO1 enhances trophoblast integrin β3 expression, and mediates cell adhesion and migration. By affecting the expression of FOXO1 and cell motility in trophoblasts, oxidative stress plays a role in the development of preeclampsia. Copyright © 2018 Elsevier Inc. All rights reserved.

Clinical implementation and evaluation of the Acuros dose calculation algorithm.

PubMed

Yan, Chenyu; Combine, Anthony G; Bednarz, Greg; Lalonde, Ronald J; Hu, Bin; Dickens, Kathy; Wynn, Raymond; Pavord, Daniel C; Saiful Huq, M

2017-09-01

The main aim of this study is to validate the Acuros XB dose calculation algorithm for a Varian Clinac iX linac in our clinics, and subsequently compare it with the wildely used AAA algorithm. The source models for both Acuros XB and AAA were configured by importing the same measured beam data into Eclipse treatment planning system. Both algorithms were validated by comparing calculated dose with measured dose on a homogeneous water phantom for field sizes ranging from 6 cm × 6 cm to 40 cm × 40 cm. Central axis and off-axis points with different depths were chosen for the comparison. In addition, the accuracy of Acuros was evaluated for wedge fields with wedge angles from 15 to 60°. Similarly, variable field sizes for an inhomogeneous phantom were chosen to validate the Acuros algorithm. In addition, doses calculated by Acuros and AAA at the center of lung equivalent tissue from three different VMAT plans were compared to the ion chamber measured doses in QUASAR phantom, and the calculated dose distributions by the two algorithms and their differences on patients were compared. Computation time on VMAT plans was also evaluated for Acuros and AAA. Differences between dose-to-water (calculated by AAA and Acuros XB) and dose-to-medium (calculated by Acuros XB) on patient plans were compared and evaluated. For open 6 MV photon beams on the homogeneous water phantom, both Acuros XB and AAA calculations were within 1% of measurements. For 23 MV photon beams, the calculated doses were within 1.5% of measured doses for Acuros XB and 2% for AAA. Testing on the inhomogeneous phantom demonstrated that AAA overestimated doses by up to 8.96% at a point close to lung/solid water interface, while Acuros XB reduced that to 1.64%. The test on QUASAR phantom showed that Acuros achieved better agreement in lung equivalent tissue while AAA underestimated dose for all VMAT plans by up to 2.7%. Acuros XB computation time was about three times faster than AAA for VMAT plans, and computation time for other plans will be discussed at the end. Maximum difference between dose calculated by AAA and dose-to-medium by Acuros XB (Acuros_D m,m ) was 4.3% on patient plans at the isocenter, and maximum difference between D 100 calculated by AAA and by Acuros_D m,m was 11.3%. When calculating the maximum dose to spinal cord on patient plans, differences between dose calculated by AAA and Acuros_D m,m were more than 3%. Compared with AAA, Acuros XB improves accuracy in the presence of inhomogeneity, and also significantly reduces computation time for VMAT plans. Dose differences between AAA and Acuros_D w,m were generally less than the dose differences between AAA and Acuros_D m,m . Clinical practitioners should consider making Acuros XB available in clinics, however, further investigation and clarification is needed about which dose reporting mode (dose-to-water or dose-to-medium) should be used in clinics. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Shared Genetic Risk Factors of Intracranial, Abdominal, and Thoracic Aneurysms.

PubMed

van 't Hof, Femke N G; Ruigrok, Ynte M; Lee, Cue Hyunkyu; Ripke, Stephan; Anderson, Graig; de Andrade, Mariza; Baas, Annette F; Blankensteijn, Jan D; Böttinger, Erwin P; Bown, Matthew J; Broderick, Joseph; Bijlenga, Philippe; Carrell, David S; Crawford, Dana C; Crosslin, David R; Ebeling, Christian; Eriksson, Johan G; Fornage, Myriam; Foroud, Tatiana; von Und Zu Fraunberg, Mikael; Friedrich, Christoph M; Gaál, Emília I; Gottesman, Omri; Guo, Dong-Chuan; Harrison, Seamus C; Hernesniemi, Juha; Hofman, Albert; Inoue, Ituro; Jääskeläinen, Juha E; Jones, Gregory T; Kiemeney, Lambertus A L M; Kivisaari, Riku; Ko, Nerissa; Koskinen, Seppo; Kubo, Michiaki; Kullo, Iftikhar J; Kuivaniemi, Helena; Kurki, Mitja I; Laakso, Aki; Lai, Dongbing; Leal, Suzanne M; Lehto, Hanna; LeMaire, Scott A; Low, Siew-Kee; Malinowski, Jennifer; McCarty, Catherine A; Milewicz, Dianna M; Mosley, Thomas H; Nakamura, Yusuke; Nakaoka, Hirofumi; Niemelä, Mika; Pacheco, Jennifer; Peissig, Peggy L; Pera, Joanna; Rasmussen-Torvik, Laura; Ritchie, Marylyn D; Rivadeneira, Fernando; van Rij, Andre M; Santos-Cortez, Regie Lyn P; Saratzis, Athanasios; Slowik, Agnieszka; Takahashi, Atsushi; Tromp, Gerard; Uitterlinden, André G; Verma, Shefali S; Vermeulen, Sita H; Wang, Gao T; Han, Buhm; Rinkel, Gabriël J E; de Bakker, Paul I W

2016-07-14

Intracranial aneurysms (IAs), abdominal aortic aneurysms (AAAs), and thoracic aortic aneurysms (TAAs) all have a familial predisposition. Given that aneurysm types are known to co-occur, we hypothesized that there may be shared genetic risk factors for IAs, AAAs, and TAAs. We performed a mega-analysis of 1000 Genomes Project-imputed genome-wide association study (GWAS) data of 4 previously published aneurysm cohorts: 2 IA cohorts (in total 1516 cases, 4305 controls), 1 AAA cohort (818 cases, 3004 controls), and 1 TAA cohort (760 cases, 2212 controls), and observed associations of 4 known IA, AAA, and/or TAA risk loci (9p21, 18q11, 15q21, and 2q33) with consistent effect directions in all 4 cohorts. We calculated polygenic scores based on IA-, AAA-, and TAA-associated SNPs and tested these scores for association to case-control status in the other aneurysm cohorts; this revealed no shared polygenic effects. Similarly, linkage disequilibrium-score regression analyses did not show significant correlations between any pair of aneurysm subtypes. Last, we evaluated the evidence for 14 previously published aneurysm risk single-nucleotide polymorphisms through collaboration in extended aneurysm cohorts, with a total of 6548 cases and 16 843 controls (IA) and 4391 cases and 37 904 controls (AAA), and found nominally significant associations for IA risk locus 18q11 near RBBP8 to AAA (odds ratio [OR]=1.11; P=4.1×10(-5)) and for TAA risk locus 15q21 near FBN1 to AAA (OR=1.07; P=1.1×10(-3)). Although there was no evidence for polygenic overlap between IAs, AAAs, and TAAs, we found nominally significant effects of two established risk loci for IAs and TAAs in AAAs. These two loci will require further replication. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Genetic analysis of abdominal aortic aneurysms (AAA)

DOE Office of Scientific and Technical Information (OSTI.GOV)

St. Jean, P.L.; Hart, B.K.; Zhang, X.C.

1994-09-01

The association between AAA and gender, smoking (SM), hypertension (HTN) and inguinal herniation (IH) was examined in 141 AAA probands and 139 of their 1st degree relatives with aortic exam (36 affected, 103 unaffected). There was no significant difference between age at diagnosis of affecteds and age at exam of unaffecteds. Of 181 males, 142 had AAA; of 99 females, 35 had AAA. Using log-linear modeling AAA was significantly associated at the 5% level with gender, SM and HTN but not IH. The association of AAA with SM and HTN held when males and females were analyzed separately. HTN wasmore » -1.5 times more common in both affected males and females, while SM was 1.5 and 2 times more common in affected males and females, respectively. Tests of association and linkage analyses were performed with relevant candidate genes: 3 COL3A1 polymorphisms (C/T, ALA/THR, AvaII), 2 ELN polymorphisms (SER/GLY, (CA)n), FBN1(TAAA)n, 2 APOB polymorphisms (Xbal,Ins/Del), CLB4B (CA)n, PI and markers D1S243 (CA)n, HPR (CA)n and MFD23(CA)n. The loci were genotyped in > 100 AAA probands and > 95 normal controls. No statistically significant evidence of association at the 5% level was obtained for any of the loci using chi-square test of association. 28 families with 2 or more affecteds were analyzed using the affected pedigree member method (APM) and lod-score analyses. There was no evidence for linkage with any loci using APM. Lod-score analysis under an autosomal recessive model resulted in excluding linkage (lod score < -2) of all loci to AAA at {theta}=0.0. Under an autosomal dominant model, linkage was excluded at {theta}=0.0 to ELN, APOB, CLG4B, D1S243, HPR and MFD23. The various genes previously proposed in AAA pathogenesis are neither associated nor casually related in our study population.« less

Multi-Centre Study on Cardiovascular Risk Management on Patients Undergoing AAA Surveillance.

PubMed

Saratzis, A; Dattani, N; Brown, A; Shalhoub, J; Bosanquet, D; Sidloff, D; Stather, P

2017-07-01

The risk of cardiovascular events and death in patients with abdominal aortic aneurysms (AAA) is high. Screening has been introduced to reduce AAA related mortality; however, after AAA diagnosis, cardiovascular modification may be as important to patient outcomes as surveillance. The aim of this study was to assess cardiovascular risk reduction in patients with small AAA. Institutional approval was granted for The Vascular and Endovascular Research Network (VERN) to retrospectively collect data pertaining to cardiovascular risk reduction from four tertiary vascular units in England. Patients with small AAA (January 2013-December 2015) were included. Demographic details, postcode, current medications, and smoking status were recorded using a bespoke electronic database and analysed. In a secondary analysis VERN contacted all AAA screening units in England and Wales to assess their current protocols relating to CV protection. In total, 1053 patients were included (mean age 74 ± 9 years, all men). Of these, 745 patients (70.8%) had been prescribed an antiplatelet agent and 787 (74.7%) a statin. Overall, only 666 patients (63.2%) were prescribed both a statin and antiplatelet. Two hundred and sixty eight patients (32.1%) were current smokers and the proportion of patients who continued to smoke decreased with age. Overall, only 401 patients (48.1%) were prescribed a statin, antiplatelet, and had stopped smoking. In the secondary analysis 38 AAA screening units (84% national coverage) replied. Thirty-one units (82%) suggest changes to the patient's prescription; however, none monitor compliance with these recommendations or assess whether the general practitioner has been made aware of the AAA diagnosis or prescription advice. Many patients with small AAA are not prescribed an antiplatelet/statin, and still smoke cigarettes, and therefore remain at high risk of cardiovascular morbidity and mortality. National guidance to ensure this high risk group of patients is adequately protected from poor cardiovascular outcomes is lacking. Copyright © 2017 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Prevalence of abdominal aortic aneurysm (AAA) in a population undergoing computed tomography colonography in Canterbury, New Zealand.

PubMed

Khashram, M; Jones, G T; Roake, J A

2015-08-01

There is compelling level 1 evidence in support of screening men for abdominal aortic aneurysm (AAA) to reduce AAA mortality. However, New Zealand (NZ) lacks data on AAA prevalence, and national screening has not been implemented. The aim of this study was to determine the prevalence of AAA in a population undergoing a computed tomography colonography (CTC) for gastrointestinal symptoms. This was an observational study; all consecutive CTCs performed in three regions of the South Island of NZ over a 4 year period were reviewed. Data on abdominal and thoracic aorta diameters ≥30 mm, and iliac and femoral aneurysms ≥20 mm were recorded. Previous aortic surgical grafts or endovascular stents were also documented. Demographics, survival, and AAA related outcomes were collected and used for analysis. Included were 4,893 scans on 4,644 patients (1,933 men [41.6%], 2,711 women [58.4%]) with a median age of 69.3 years (range 17.0-97.0 years). There were 309 scans on 289 patients (75.4% men) who had either an aneurysm or a previous aortic graft with a median age of 79.6 years (range 57.0-96.0 years). Of these, 223 had a native AAA ≥30 mm. The prevalence of AAA rose with age from 1.3% in men aged 55-64 years, to 9.1% in 65-74 year olds, 16.8% in 75-84 year olds, and 22.0% in ≥85 year olds. The corresponding figures in women were 0.4%, 2%, 3.9%, and 6.2%, respectively. In this observational study, the prevalence of AAA was high and warrants further evaluation. The results acquired help to define a population that may benefit from a national AAA screening programme. Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Abdominal Aortic Aneurysm: Novel Mechanisms and Therapies

PubMed Central

Davis, Frank M.; Rateri, Debra L.; Daugherty, Alan

2015-01-01

Purpose of review Abdominal aortic aneurysm (AAA) is a pathological condition of permanent dilation that portends the potentially fatal consequence of aortic rupture. This review emphasizes recent advances in mechanistic insight into aneurysm pathogenesis and potential pharmacologic therapies that are on the horizon for AAAs. Recent Findings An increasing body of evidence demonstrates that genetic factors, including 3p12.3, DAB2IP, LDLr, LRP1, MMP3, TGFβR2 and SORT1 loci, are associated with AAA development. Current human studies and animal models have shown that many leukocytes and inflammatory mediators, such as IL-1, IL-17, TGF-β and angiotensin II, are involved in the pathogenesis of AAAs. Leukocytic infiltration into aortic media leads to smooth muscle cell depletion, generation of reactive oxygen species, and extracellular matrix fragmentation. Recent preclinical investigations into pharmacological therapies for AAAs have provided intriguing insight for roles of microRNAs to regulate many pathological pathways in AAA development. Several large clinical trials are ongoing seeking to translate preclinical findings into therapeutic options. Summary Recent studies have identified many potential mechanisms involved in AAA pathogenesis that provide insight for the development of a medical treatment for this disease. PMID:26352243

The peroxisomal AAA ATPase complex prevents pexophagy and development of peroxisome biogenesis disorders

PubMed Central

Law, Kelsey B.; Bronte-Tinkew, Dana; Di Pietro, Erminia; Snowden, Ann; Jones, Richard O.; Moser, Ann; Brumell, John H.; Braverman, Nancy

2017-01-01

ABSTRACT Peroxisome biogenesis disorders (PBDs) are metabolic disorders caused by the loss of peroxisomes. The majority of PBDs result from mutation in one of 3 genes that encode for the peroxisomal AAA ATPase complex (AAA-complex) required for cycling PEX5 for peroxisomal matrix protein import. Mutations in these genes are thought to result in a defect in peroxisome assembly by preventing the import of matrix proteins. However, we show here that loss of the AAA-complex does not prevent matrix protein import, but instead causes an upregulation of peroxisome degradation by macroautophagy, or pexophagy. The loss of AAA-complex function in cells results in the accumulation of ubiquitinated PEX5 on the peroxisomal membrane that signals pexophagy. Inhibiting autophagy by genetic or pharmacological approaches rescues peroxisome number, protein import and function. Our findings suggest that the peroxisomal AAA-complex is required for peroxisome quality control, whereas its absence results in the selective degradation of the peroxisome. Thus the loss of peroxisomes in PBD patients with mutations in their peroxisomal AAA-complex is a result of increased pexophagy. Our study also provides a framework for the development of novel therapeutic treatments for PBDs. PMID:28521612

The peroxisomal AAA ATPase complex prevents pexophagy and development of peroxisome biogenesis disorders.

PubMed

Law, Kelsey B; Bronte-Tinkew, Dana; Di Pietro, Erminia; Snowden, Ann; Jones, Richard O; Moser, Ann; Brumell, John H; Braverman, Nancy; Kim, Peter K

2017-05-04

Peroxisome biogenesis disorders (PBDs) are metabolic disorders caused by the loss of peroxisomes. The majority of PBDs result from mutation in one of 3 genes that encode for the peroxisomal AAA ATPase complex (AAA-complex) required for cycling PEX5 for peroxisomal matrix protein import. Mutations in these genes are thought to result in a defect in peroxisome assembly by preventing the import of matrix proteins. However, we show here that loss of the AAA-complex does not prevent matrix protein import, but instead causes an upregulation of peroxisome degradation by macroautophagy, or pexophagy. The loss of AAA-complex function in cells results in the accumulation of ubiquitinated PEX5 on the peroxisomal membrane that signals pexophagy. Inhibiting autophagy by genetic or pharmacological approaches rescues peroxisome number, protein import and function. Our findings suggest that the peroxisomal AAA-complex is required for peroxisome quality control, whereas its absence results in the selective degradation of the peroxisome. Thus the loss of peroxisomes in PBD patients with mutations in their peroxisomal AAA-complex is a result of increased pexophagy. Our study also provides a framework for the development of novel therapeutic treatments for PBDs.

The preventive and curative effects of melatonin against abdominal aortic aneurysm in rats.

PubMed

Tekin, Gözde; İsbir, Selim; Şener, Göksel; Çevik, Özge; Çetinel, Şule; Dericioğlu, Okan; Arsan, Sinan; Çobanoğlu, Adnan

2018-05-01

Oxygen free radicals are important components involved in the histopathologic tissue alterations observed during abdominal aortic aneurysms (AAAs). This study examined whether melatonin has protective or therapeutic effects against AAAs. Sprague-Dawley rats were divided into four groups. A CaCl 2 model was used to induce AAA. Starting on the operation day (Mel+AAA+Mel group) or 4 weeks after the operation (AAA+Mel group), the rats received intraperitoneal melatonin (10 mg/kg/day) for 6 and 2 weeks, respectively. The control and AAA groups received vehicle for 2 weeks after the sham operation and AAA induction, respectively. Angiographic measurements were recorded at the beginning, week 4, and week 6 of the study. After decapitation, aorta tissues were taken for the measurement of malondialdehyde, 8-hydroxy-2'-deoxyguanosine, glutathione levels, and myeloperoxidase and caspase-3 activity. Matrix metalloproteinase (MMP)-2, MMP-9, tumor necrosis factor-α, and inducible nitric oxide synthase protein expressions were analyzed by Western blot technique. Aortic tissues were also examined by light microscopy. CaCl 2 caused an inflammatory response and oxidative damage indicated by rises in malondialdehyde and 8-hydroxy-2'-deoxyguanosine levels. Myeloperoxidase and caspase-3 activities were increased, but glutathione levels were reduced. On the one hand, MMP-2, MMP-9, tumor necrosis factor-α, and inducible nitric oxide synthase protein expressions were increased in the vehicle-treated AAA group. On the other hand, melatonin treatment reversed all of these biochemical indices and histopathologic alterations. According to the data, although melatonin tended to reverse the biochemical parameters given on week 4, the preventive effect is more pronounced when given concomitantly with AAA induction because values were closer to the control levels. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Awake Craniotomy Anesthesia: A Comparison of the Monitored Anesthesia Care and Asleep-Awake-Asleep Techniques.

PubMed

Eseonu, Chikezie I; ReFaey, Karim; Garcia, Oscar; John, Amballur; Quiñones-Hinojosa, Alfredo; Tripathi, Punita

2017-08-01

Commonly used sedation techniques for an awake craniotomy include monitored anesthesia care (MAC), using an unprotected airway, and the asleep-awake-asleep (AAA) technique, using a partially or totally protected airway. We present a comparative analysis of the MAC and AAA techniques, evaluating anesthetic management, perioperative outcomes, and complications in a consecutive series of patients undergoing the removal of an eloquent brain lesion. Eighty-one patients underwent awake craniotomy for an intracranial lesion over a 9-year period performed by a single-surgeon and a team of anesthesiologists. Fifty patients were treated using the MAC technique, and 31 were treated using the AAA technique. A retrospective analysis evaluated anesthetic management, intraoperative complications, postoperative outcomes, pain management, and complications. The MAC and AAA groups had similar preoperative patient and tumor characteristics. Mean operative time was shorter in the MAC group (283.5 minutes vs. 313.3 minutes; P = 0.038). Hypertension was the most common intraoperative complication seen (8% in the MAC group vs. 9.7% in the AAA group; P = 0.794). Intraoperative seizure occurred at a rate of 4% in the MAC group and 3.2% in the AAA group (P = 0.858). Awake cases were converted to general anesthesia in no patients in the MAC group and in 1 patient (3.2%) in the AAA group (P = 0.201). No cases were aborted in either group. The mean hospital length of stay was 3.98 days in the MAC group and 3.84 days in the AAA group (P = 0.833). Both the MAC and AAA sedation techniques provide an efficacious and safe method for managing awake craniotomy cases and produce similar perioperative outcomes, with the MAC technique associated with shorter operative time. Copyright © 2017 Elsevier Inc. All rights reserved.

Ultraviolet B Exposure Inhibits Angiotensin II-Induced Abdominal Aortic Aneurysm Formation in Mice by Expanding CD4+Foxp3+ Regulatory T Cells.

PubMed

Hayashi, Tomohiro; Sasaki, Naoto; Yamashita, Tomoya; Mizoguchi, Taiji; Emoto, Takuo; Amin, Hilman Zulkifli; Yodoi, Keiko; Matsumoto, Takuya; Kasahara, Kazuyuki; Yoshida, Naofumi; Tabata, Tokiko; Kitano, Naoki; Fukunaga, Atsushi; Nishigori, Chikako; Rikitake, Yoshiyuki; Hirata, Ken-Ichi

2017-08-31

Pathogenic immune responses are known to play an important role in abdominal aortic aneurysm (AAA) development. Ultraviolet B (UVB) irradiation has been demonstrated to have therapeutic potential not only for cutaneous diseases but also for systemic inflammatory diseases in mice by suppressing immunoinflammatory responses. We investigated the effect of UVB irradiation on experimental AAA. We used an angiotensin II-induced AAA model in apolipoprotein E-deficient mice fed a high-cholesterol diet. Mice aged 10 weeks were irradiated with 5 kJ/m 2 UVB once weekly for 6 weeks (UVB-irradiated, n=38; nonirradiated, n=42) and were euthanized for evaluation of AAA formation at 16 weeks. Overall, 93% of angiotensin II-infused mice developed AAA, with 60% mortality possibly because of aneurysm rupture. UVB irradiation significantly decreased the incidence (66%) and mortality (29%) of AAA ( P =0.004 and P =0.006, respectively). UVB-irradiated mice had significantly smaller diameter AAA ( P =0.008) and fewer inflammatory cells in the aortic aneurysm tissue than nonirradiated mice, along with systemic expansion of CD4 + Foxp3 + regulatory T cells and decreased effector CD4 + CD44 high CD62L low T cells in para-aortic lymph nodes. Genetic depletion of regulatory T cells abrogated these beneficial effects of UVB treatment, demonstrating a critical role of regulatory T cells. Our data suggest that UVB-dependent expansion of regulatory T cells has beneficial effects on experimental AAA and may provide a novel strategy for the treatment of AAA. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Electron cryomicroscopy structure of a membrane-anchored mitochondrial AAA protease.

PubMed

Lee, Sukyeong; Augustin, Steffen; Tatsuta, Takashi; Gerdes, Florian; Langer, Thomas; Tsai, Francis T F

2011-02-11

FtsH-related AAA proteases are conserved membrane-anchored, ATP-dependent molecular machines, which mediate the processing and turnover of soluble and membrane-embedded proteins in eubacteria, mitochondria, and chloroplasts. Homo- and hetero-oligomeric proteolytic complexes exist, which are composed of homologous subunits harboring an ATPase domain of the AAA family and an H41 metallopeptidase domain. Mutations in subunits of mitochondrial m-AAA proteases have been associated with different neurodegenerative disorders in human, raising questions on the functional differences between homo- and hetero-oligomeric AAA proteases. Here, we have analyzed the hetero-oligomeric yeast m-AAA protease composed of homologous Yta10 and Yta12 subunits. We combined genetic and structural approaches to define the molecular determinants for oligomer assembly and to assess functional similarities between Yta10 and Yta12. We demonstrate that replacement of only two amino acid residues within the metallopeptidase domain of Yta12 allows its assembly into homo-oligomeric complexes. To provide a molecular explanation, we determined the 12 Å resolution structure of the intact yeast m-AAA protease with its transmembrane domains by electron cryomicroscopy (cryo-EM) and atomic structure fitting. The full-length m-AAA protease has a bipartite structure and is a hexamer in solution. We found that residues in Yta12, which facilitate homo-oligomerization when mutated, are located at the interface between neighboring protomers in the hexamer ring. Notably, the transmembrane and intermembrane space domains are separated from the main body, creating a passage on the matrix side, which is wide enough to accommodate unfolded but not folded polypeptides. These results suggest a mechanism regarding how proteins are recognized and degraded by m-AAA proteases.

Obesity is not an independent risk factor for adverse perioperative and long-term clinical outcomes following open AAA repair or EVAR.

PubMed

Park, Brian; Dargon, Phong; Binette, Christopher; Babic, Bruna; Thomas, Tina; Divinagracia, Thomas; Dahn, Michael S; Menzoian, James O

2011-10-01

Moderate (body mass index [BMI] ≥30) and morbid obesity (BMI ≥35) is increasing at an alarming rate in vascular surgery patients. The objective of this study was to determine the impact of obesity on perioperative and long-term clinical outcomes following open abdominal aortic aneurysm (AAA) repair or endovascular aneurysm repair (EVAR). This review includes patients that underwent open AAA repair (n = 403) or EVAR (n = 223) from 1999 to 2009. Specific patient characteristics such as comorbid diseases, medications, and body mass index (BMI) were assessed. Specific perioperative outcomes such as length of stay, myocardial infarctions, and mortality were reviewed. In addition, long-term outcomes such as rates of reintervention, permanent renal dysfunction, and mortality beyond 30 days were also assessed. The incidence of obesity in open AAA patients was 25.3% (documented incidence 1.5%) and for EVAR was 24.6% (documented incidence 4%). Moderate and morbid obesity was associated with longer intensive care unit (ICU) admissions for both open AAA or EVAR patients (P < .05). However, no significant differences in perioperative outcomes in terms of overall length of stay, myocardial infarction, acute renal failure, wound infections, or mortality were noted between obese and nonobese patients underoing open AAA repair or EVAR (P > .05). Similarly, moderate and morbid obesity was not associated with significant differences in rates of reintervention, permanent renal dysfunction, and mortality beyond 30 days for patients undergoing open AAA repair or EVAR (P > .05). The results of this study indicate that moderate and morbid obesity are not independently associated with adverse perioperative and long-term clinical outcomes for patients undergoing open AAA repair or EVAR. Therefore, either open AAA repair or EVAR can be accomplished safely in moderately obese and morbidly obese patients.

Evaluation of the relationship between plasma lipids and abdominal aortic aneurysm: A Mendelian randomization study.

PubMed

Weng, Lu-Chen; Roetker, Nicholas S; Lutsey, Pamela L; Alonso, Alvaro; Guan, Weihua; Pankow, James S; Folsom, Aaron R; Steffen, Lyn M; Pankratz, Nathan; Tang, Weihong

2018-01-01

Studies have reported that higher circulating levels of total cholesterol (TC), low-density lipoprotein (LDL) cholesterol and lower of high-density lipoprotein (HDL) cholesterol may be associated with increased risk of abdominal aortic aneurysm (AAA). Whether dyslipidemia causes AAA is still unclear and is potentially testable using a Mendelian randomization (MR) approach. We investigated the associations between blood lipids and AAA using two-sample MR analysis with SNP-lipids association estimates from a published genome-wide association study of blood lipids (n = 188,577) and SNP-AAA association estimates from European Americans (EAs) of the Atherosclerosis Risk in Communities (ARIC) study (n = 8,793). We used inverse variance weighted (IVW) MR as the primary method and MR-Egger regression and weighted median MR estimation as sensitivity analyses. Over a median of 22.7 years of follow-up, 338 of 8,793 ARIC participants experienced incident clinical AAA. Using the IVW method, we observed positive associations of plasma LDL cholesterol and TC with the risk of AAA (odds ratio (OR) = 1.55, P = 0.02 for LDL cholesterol and OR = 1.61, P = 0.01 for TC per 1 standard deviation of lipid increment). Using the MR-Egger regression and weighted median methods, we were able to validate the association of AAA risk with TC, although the associations were less consistent for LDL cholesterol due to wider confidence intervals. Triglycerides and HDL cholesterol were not associated with AAA in any of the MR methods. Assuming instrumental variable assumptions are satisfied, our finding suggests that higher plasma TC and LDL cholesterol are causally associated with the increased risk of AAA in EAs.

Impact of surgeon and hospital experience on outcomes of abdominal aortic aneurysm repair in New York State.

PubMed

Meltzer, Andrew J; Connolly, Peter H; Schneider, Darren B; Sedrakyan, Art

2017-09-01

This study aimed to assess the impact of the surgeon's and hospital's experience on the outcomes of open surgical repair (OSR) and endovascular aneurysm repair (EVAR) of intact and ruptured abdominal aortic aneurysms (AAAs) in New York State. New York Statewide Planning and Research Cooperative System data were used to identify patients undergoing AAA repair from 2000 to 2011. Characteristics of the provider and hospital were determined by linkage to the New York Office of Professions and National Provider Identification databases. Distinct hierarchical logistic regression models for EVAR and OSR for intact and ruptured AAAs were created to adjust for the patient's comorbidities and to evaluate the impact of the surgeon's and hospital's experience on outcomes. The provider's years since medical school graduation as well as annual volume of the facility and provider are examined in tertiles. Adjusted odds ratios and 95% confidence intervals are presented. A total of 18,842 patients underwent AAA repair by a vascular surgeon. For intact AAAs (n = 17,118), 26.2% of patients underwent OSR and 73.8% underwent EVAR. For ruptured AAAs (n = 1724), 63.9% underwent OSR and 36.1% underwent EVAR. After intact AAA repair, OSR adjusted outcomes were significantly influenced by the surgeon's annual volume but not by the facility's volume or the surgeon's age. The lowest volume providers (1-4 OSRs) had higher in-hospital mortality rates than high-volume (>11 OSRs) surgeons (adjusted odds ratio, 1.87 [95% confidence interval, 1.1-3.17]). Low-volume providers also had higher odds of major complications (1.23 [1-1.51]). For patients with intact AAA undergoing EVAR, mortality was higher at low-volume facilities (2.6 [1.3-5.3] and 2.7 [1.5-4.8] for <33 EVARs and 34-81 EVARs, respectively). After OSR for ruptured AAA, treatment at a low-volume facility (<9 OSRs for ruptured AAA) was associated with greater mortality than at high-volume (>27 OSRs for ruptured AAA) centers (1.56 [1.02-2.39]), whereas low-volume physicians (<4 OSRs for ruptured AAA) had higher odds of major complications (1.58 [1.04-2.41]). In the case of EVAR for rupture, there were no characteristics of the hospital or surgeon significantly associated with poorer outcomes. For intact AAA, the surgeon's volume was an important factor for OSR outcomes, whereas low facility volume was associated with worse outcomes after EVAR. For ruptured AAA, low-volume surgeons and low-volume facilities had worse outcomes after OSR but not after EVAR. The interaction between the surgeon's volume and the hospital's volume is complex and varies on the basis of the acuity of presentation and treatment modality. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

A Computational Model for Biomechanical Effects of Arterial Compliance Mismatch

PubMed Central

He, Fan; Hua, Lu; Gao, Li-jian

2015-01-01

Background. Compliance mismatch is a negative factor and it needs to be considered in arterial bypass grafting. Objective. A computational model was employed to investigate the effects of arterial compliance mismatch on blood flow, wall stress, and deformation. Methods. The unsteady blood flow was assumed to be laminar, Newtonian, viscous, and incompressible. The vessel wall was assumed to be linear elastic, isotropic, and incompressible. The fluid-wall interaction scheme was constructed using the finite element method. Results. The results show that there are identical wall shear stress waveforms, wall stress, and strain waveforms at different locations. The comparison of the results demonstrates that wall shear stresses and wall strains are higher while wall stresses are lower at the more compliant section. The differences promote the probability of intimal thickening at some locations. Conclusions. The model is effective and gives satisfactory results. It could be extended to all kinds of arteries with complicated geometrical and material factors. PMID:27019580

Fundamental Characteristics of AAA+ Protein Family Structure and Function

PubMed Central

2016-01-01

Many complex cellular events depend on multiprotein complexes known as molecular machines to efficiently couple the energy derived from adenosine triphosphate hydrolysis to the generation of mechanical force. Members of the AAA+ ATPase superfamily (ATPases Associated with various cellular Activities) are critical components of many molecular machines. AAA+ proteins are defined by conserved modules that precisely position the active site elements of two adjacent subunits to catalyze ATP hydrolysis. In many cases, AAA+ proteins form a ring structure that translocates a polymeric substrate through the central channel using specialized loops that project into the central channel. We discuss the major features of AAA+ protein structure and function with an emphasis on pivotal aspects elucidated with archaeal proteins. PMID:27703410

Fenestrated endovascular aortic repair and clinical trial devices for complex abdominal aortic aneurysms.

PubMed

Brinster, Clayton J; Milner, Ross

2018-06-01

Endovascular aortic repair (EVAR) has revolutionized the treatment of infrarenal abdominal aortic aneurysm (AAA), with consistently low reported perioperative morbidity and mortality. Universal applicability of EVAR to treat AAA is hindered by several specific anatomic constraints, however, and many patients cannot be treated with commercially available stent-grafts within the device specific instructions for use. Treatment of these complex pararenal aneurysms is increasingly accomplished by extension of EVAR into the visceral segment of the abdominal aorta with branches or fenestrations that allow perfusion of the visceral and renal arteries. Fenestrated endovascular aneurysm repair (FEVAR) was initially developed to treat high-risk patients unfit for open surgery and anatomically ineligible for standard infrarenal EVAR, but this technique has evolved over the past decade into a mature treatment option for complex AAA. High-volume, single-center reports, multicenter series and clinical reviews have demonstrated that FEVAR is a safe and effective technique with favorable results at proficient centers. Generalizability of these outcomes to less advanced centers remains unproven, and reintervention rates following FEVAR in the mid- and long-term, even among the most experienced centers, remain a concern. Several off-the-shelf devices that are undergoing clinical trial seek to broaden the anatomic applicability and overall availability of FEVAR. A significant number of patients are not candidates for off-the-shelf or customized stent-grafts, however, stressing the need for continued refinement of existing devices, development of novel devices with broader indications for use, and maintenance of open surgical skills.

A Near-Wall Reynolds-Stress Closure without Wall Normals

NASA Technical Reports Server (NTRS)

Yuan, S. P.; So, R. M. C.

1997-01-01

With the aid of near-wall asymptotic analysis and results of direct numerical simulation, a new near-wall Reynolds stress model (NNWRS) is formulated based on the SSG high-Reynolds-stress model with wall-independent near-wall corrections. Only one damping function is used for flows with a wide range of Reynolds numbers to ensure that the near-wall modifications diminish away from the walls. The model is able to reproduce complicated flow phenomena induced by complex geometry, such as flow recirculation, reattachment and boundary-layer redevelopment in backward-facing step flow and secondary flow in three-dimensional square duct flow. In simple flows, including fully developed channel/pipe flow, Couette flow and boundary-layer flow, the wall effects are dominant, and the NNWRS model predicts less degree of turbulent anisotropy in the near-wall region compared with a wall-dependent near-wall Reynolds Stress model (NWRS) developed by So and colleagues. The comparison of the predictions given by the two models rectifies the misconception that the overshooting of skin friction coefficient in backward-facing step flow prevalent in those near-wall, models with wall normal is caused by he use of wall normal.

Structural Basis for Disassembly of Katanin Heterododecamers.

PubMed

Nithianantham, Stanley; McNally, Francis J; Al-Bassam, Jawdat

2018-05-11

The reorganization of microtubules in mitosis, meiosis and development requires the microtubule-severing activity of katanin.  Katanin is a heterodimer composed of an ATPase Associated with diverse cellular Activities (AAA) subunit and a regulatory subunit. Microtubule severing requires ATP hydrolysis by katanin's conserved AAA ATPase domains. Whereas other AAA ATPases form stable hexamers, we show that katanin only forms monomer or dimers of heterodimers in solution.  Katanin oligomers consistent with hexamers of heterodimers or heterododecamers were only observed for an ATP hydrolysis deficient mutant in the presence of ATP.  X-ray structures of katanin's AAA ATPase in monomeric nucleotide-free and pseudo-oligomeric ADP-bound states reveal conformational changes in AAA subdomains that explained the structural basis for instability of katanin heterododecamer.  We propose that the rapid dissociation of katanin AAA oligomers may lead to an auto-inhibited state that prevents inappropriate microtubule severing, or that cyclical disassembly into heterodimers may critically contribute to the microtubule-severing mechanism. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

A Non-Competitive Inhibitor of VCP/p97 and VPS4 Reveals Conserved Allosteric Circuits in Type I and II AAA ATPases.

PubMed

Pöhler, Robert; Krahn, Jan H; van den Boom, Johannes; Dobrynin, Grzegorz; Kaschani, Farnusch; Eggenweiler, Hans-Michael; Zenke, Frank T; Kaiser, Markus; Meyer, Hemmo

2018-02-05

AAA ATPases have pivotal functions in diverse cellular processes essential for survival and proliferation. Revealing strategies for chemical inhibition of this class of enzymes is therefore of great interest for the development of novel chemotherapies or chemical tools. Here, we characterize the compound MSC1094308 as a reversible, allosteric inhibitor of the type II AAA ATPase human ubiquitin-directed unfoldase (VCP)/p97 and the type I AAA ATPase VPS4B. Subsequent proteomic, genetic and biochemical studies indicate that MSC1094308 binds to a previously characterized drugable hotspot of p97, thereby inhibiting the D2 ATPase activity. Our results furthermore indicate that a similar allosteric site exists in VPS4B, suggesting conserved allosteric circuits and drugable sites in both type I and II AAA ATPases. Our results may thus guide future chemical tool and drug discovery efforts for the biomedically relevant AAA ATPases. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Pathophysiology of AAA: heredity vs environment.

PubMed

Björck, Martin; Wanhainen, Anders

2013-01-01

Abdominal aortic aneurysm (AAA) has a complex pathophysiology, in which both environmental and genetic factors play important roles, the most important being smoking. The recently reported falling prevalence rates of AAA in northern Europe and Australia/New Zeeland are largely explained by healthier smoking habits. Dietary factors and obesity, in particular abdominal obesity, are also of importance. A family history of AAA among first-degree relatives is present in approximately 13% of incident cases. The probability that a monozygotic twin of a person with an AAA has the disease is 24%, 71 times higher than that for a monozygotic twin of a person without AAA. Approximately 1000 SNPs in 100 candidate genes have been studied, and three genome-wide association studies were published, identifying different diverse weak associations. An example of interaction between environmental and genetic factors is the effect of cholesterol, where genetic and dietary factors affect levels of both HDL and LDL. True epigenetic studies have not yet been published. Copyright © 2013 Elsevier Inc. All rights reserved.

Near-wall similarity in a pressure-driven three-dimensional turbulent boundary layer

NASA Technical Reports Server (NTRS)

Pierce, F. J.; Mcallister, J. E.

1980-01-01

Mean velocity, measured wall pressure and wall shear stress fields were made in a three dimensional pressure-driven turbulent boundary layer created by a cylinder with trailing edge placed normal to a flat plate floor. The direct force wall shear stress measurements were made with floating element direct force sensing shear meter that responded to both the magnitude and direction of the local wall shear stress. The ability of 10 near wall similarity models to describe the near wall velocity field for the measured flow under a wide range of skewing conditions and a variety of pressure gradient and wall shear vector orientations was used.

Outcomes for Symptomatic Abdominal Aortic Aneurysms in the American College of Surgeons National Surgical Quality Improvement Program (NSQIP)

PubMed Central

Soden, Peter A.; Zettervall, Sara L.; Ultee, Klaas H.J.; Darling, Jeremy D.; Buck, Dominique B.; Hile, Chantel N.; Hamdan, Allen D.; Schermerhorn, Marc L.

2016-01-01

Introduction Historically symptomatic AAAs were found to have intermediate mortality compared to asymptomatic and ruptured AAAs but, with wider EVAR use, a more recent study suggested mortality of symptomatic aneurysms were similar to asymptomatic AAAs. These prior studies were limited by small numbers. The purpose of this study is to evaluate the mortality and morbidity associated with symptomatic AAA repair in a large contemporary population. Methods All patients undergoing infrarenal AAA repair were identified in the 2011–2013 ACS-NSQIP, Vascular Surgery targeted module. We excluded acute conversions to open repair and those for whom the surgical indication was embolization, dissection, thrombosis, or not documented. We compared 30-day mortality and major adverse events (MAE) for asymptomatic, symptomatic, and ruptured AAA repair, stratified by EVAR and open repair, with univariate analysis and multivariable logistic regression. Results 5502 infrarenal AAAs were identified, 4495 asymptomatic (830 open repair, 3665 [82%] EVAR), 455 symptomatic (143 open, 312 [69%] EVAR), and 552 ruptured aneurysms (263 open, 289 [52%] EVAR). Aneurysm diameter was similar between asymptomatic and symptomatic AAAs, when stratified by procedure type, but larger for ruptured aneurysms (EVAR symptomatic 5.8cm ±1.6 vs. ruptured 7.5cm ±2.0, P<.001; open repair symptomatic 6.4cm ±1.9 vs. ruptured 8.0cm ±1.9, P<.001). The proportion of females was similar in symptomatic and ruptured AAA (27% vs. 23%, P=.14, respectively), but lower in asymptomatic AAA (20%, P<.001). Symptomatic AAAs had intermediate 30-day mortality compared to asymptomatic and ruptured aneurysms after both EVAR (asymptomatic 1.4% vs. symptomatic 3.8%, P=.001; symptomatic vs. 22% ruptured, P<.001) and open repair (asymptomatic 4.3% vs. symptomatic 7.7% , P=.08; symptomatic vs. 57% ruptured, P<.001). After adjustment for age, gender, repair type, dialysis dependence, and history of severe COPD, patients undergoing repair of symptomatic AAAs were twice as likely to die within 30-days compared to those with asymptomatic aneurysms (OR 2.1, 95%CI 1.3–3.5). When stratified by repair type the effect size and direction of the odds ratios were similar (EVAR OR 2.4, CI 1.2–4.7; open repair OR 1.8, CI 0.86–3.9), although not significant for open repair. Patients with ruptured aneurysms had a sevenfold increased risk of 30-day mortality compared to symptomatic patients (OR 6.5, CI 4.1–10.6). Conclusion Patients with symptomatic AAAs had a two-fold increased risk of perioperative mortality, compared to asymptomatic aneurysms undergoing repair. Furthermore, patients with ruptured aneurysms have a seven-fold increased risk of mortality compared to symptomatic aneurysms. PMID:27146791

Simultaneous repair of abdominal aortic aneurysm and resection of unexpected, associated abdominal malignancies.

PubMed

Illuminati, Giulio; Calio', Francesco G; D'Urso, Antonio; Lorusso, Riccardo; Ceccanei, Gianluca; Vietri, Francesco

2004-12-15

The management of unexpected intra-abdominal malignancy, discovered at laparotomy for elective treatment of an abdominal aortic aneurysm (AAA), is controversial. It is still unclear whether both conditions should be treated simultaneously or a staged approach is to be preferred. To contribute in improving treatment guidelines, we retrospectively reviewed the records of patients undergoing laparotomy for elective AAA repair. From January 1994 to March 2003, 253 patients underwent elective, trans-peritoneal repair of an AAA. In four patients (1.6%), an associated, unexpected neoplasm was detected at abdominal exploration, consisting of one renal, one gastric, one ileal carcinoid, and one ascending colon tumor. All of them were treated at the same operation, after aortic repair and careful isolation of the prosthetic graft. The whole series' operative mortality was 3.6%. None of the patients simultaneously treated for AAA and tumor resection died in the postoperative period. No graft-related infections were observed. Simultaneous treatment of AAA and tumor did not prolong significantly the mean length of stay in the hospital, compared to standard treatment of AAA alone. Except for malignancies of organs requiring major surgical resections, simultaneous AAA repair and resection of an associated, unexpected abdominal neoplasm can be safely performed, in most of the patients, sparing the need for a second procedure. Endovascular grafting of the AAA can be a valuable tool in simplifying simultaneous treatment, or in staging the procedures with a very short delay.

Functional characterization of T cells in abdominal aortic aneurysms.

PubMed

Forester, Nerys D; Cruickshank, Sheena M; Scott, D Julian A; Carding, Simon R

2005-06-01

Abdominal aortic aneurysms (AAA) exhibit features of a chronic inflammatory disorder. The functional attributes of the T cells in AAA tissue are unclear, with little quantitative or functional data. Using a novel, non-enzymatic method to isolate viable cells from AAA tissue, functional properties of AAA T cells were investigated for the first time. Composition and phenotype of AAA T cells was determined by flow cytometry and verified by immunohistochemistry. Tissue mononuclear cells (MNCs) were cultured in the presence of T-cell mitogens, and cell cycle analysis and cytokine production assessed. Typical cell yield was 4.5 x 10(6) cells per gram of AAA tissue. The majority (58.1+/-5.3%) of haematopoietic (CD45+) cells recovered were CD3+ T cells, B cells comprised 41.1+/-5.7%, natural killer cells 7.3+/-2.5%, and macrophages 2%. Freshly isolated T cells were in resting (G1) state, with 25% expressing the activation-associated cell surface antigens major histocompatibility complex II and CD25. When stimulated in vitro, a significant proportion entered S and G2 phase of the cell cycle, up-regulated CD25, and secreted tumour necrosis factor-alpha, interferon-gamma, interleukin (IL)-5 and IL-6. Despite patient differences, the composition of the AAA inflammatory infiltrate was remarkably consistent, and when re-stimulated ex-vivo T cells produced a stereotypical cytokine response, consistent with the hypothesis that AAA T cells can promote tissue inflammation by secretion of proinflammatory cytokines, and in addition provide signals for B-cell help.

Distinct Effect of Benzalkonium Chloride on the Esterase and Aryl Acylamidase Activities of Butyrylcholinesterase.

PubMed

Jaganathan; Boopathy

2000-08-01

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) from vertebrates, other than their predominant acylcholine hydrolase (esterase) activity, display a genuine aryl acylamidase activity (AAA) capable of hydrolyzing the synthetic substrate o-nitroacetanilide to o-nitroaniline. This AAA activity is strongly inhibited by classical cholinesterase (ChE) inhibitors. In the present study, benzalkonium chloride (BAC), a cationic detergent widely used as a preservative in pharmaceutical preparations, has been shown to distinctly modulate the esterase and AAA activities of BChEs. The detergent BAC was able to inhibit the esterase activity of human serum and horse serum BChEs and AChEs from electric eel and human erythrocyte. The remarkable property of BAC was its ability to profoundly activate the AAA activity of human serum and horse serum BChEs but not the AAA activity of AChEs. Thus BAC seem to preferentially activate the AAA activity of BChEs alone. Results of the study using the ChE active site-specific inhibitor diisopropyl phosphorofluoridate indicated that BAC binds to the active site of ChEs. Furthermore, studies using a structural homolog of BAC indicated that the alkyl group of BAC is essential not only for its interaction with ChEs but also for its distinct effect on the esterase and AAA activities of BChEs. This is the first report of a compound that inhibits the esterase activity, while simultaneously activating the AAA activity, of BChEs. Copyright 2000 Academic Press.

Peptide inhibitor of CXCL4-CCL5 heterodimer formation, MKEY, inhibits experimental aortic aneurysm initiation and progression.

PubMed

Iida, Yasunori; Xu, Baohui; Xuan, Haojun; Glover, Keith J; Tanaka, Hiroki; Hu, Xiaolei; Fujimura, Naoki; Wang, Wei; Schultz, Joshua R; Turner, Court R; Dalman, Ronald L

2013-04-01

Macrophages are critical contributors to abdominal aortic aneurysm (AAA) disease. We examined the ability of MKEY, a peptide inhibitor of CXCL4-CCL5 interaction, to influence AAA progression in murine models. AAAs were created in 10-week-old male C57BL/6J mice by transient infrarenal aortic porcine pancreatic elastase infusion. Mice were treated with MKEY via intravenous injection either (1) before porcine pancreatic elastase infusion or (2) after aneurysm initiation. Immunostaining demonstrated CCL5 and CCR5 expression on aneurysmal aortae and mural monocytes/macrophages, respectively. MKEY treatment partially inhibited migration of adaptively transferred leukocytes into aneurysmal aortae in recipient mice. Although all vehicle-pretreated mice developed AAAs, aneurysms formed in only 60% (3/5) and 14% (1/7) of mice pretreated with MKEY at 10 and 20 mg/kg, respectively. MKEY pretreatment reduced aortic diameter enlargement, preserved medial elastin fibers and smooth muscle cells, and attenuated mural macrophage infiltration, angiogenesis, and aortic metalloproteinase 2 and 9 expression after porcine pancreatic elastase infusion. MKEY initiated after porcine pancreatic elastase infusion also stabilized or reduced enlargement of existing AAAs. Finally, MKEY treatment was effective in limiting AAA formation after angiotensin II infusion in apolipoprotein E-deficient mice. MKEY suppresses AAA formation and progression in 2 complementary experimental models. Peptide inhibition of CXCL4-CCL5 interactions may represent a viable translational strategy to limit progression of human AAA disease.

SU-F-T-413: Calculation Accuracy of AAA and Acuros Using Cerrobend Blocks for TBI at 400cm

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lamichhane, N; Studenski, M

2016-06-15

Purpose: It is essential to assess the lung dose during TBI to reduce toxicity. Here we characterize the accuracy of the AAA and Acuros algorithms when using cerrobend lung shielding blocks at an extended distance for TBI. Methods: We positioned a 30×30×30 cm3 solid water slab phantom at 400 cm SSD and measured PDDs (Exradin A12 and PTW parallel plate ion chambers). A 2 cm thick, 10×10 cm2 cerrobend block was hung 2 cm in front of the phantom. This geometry was reproduced in the planning system for both AAA and Acuros. In AAA, the mass density of the cerrobendmore » block was forced to 9.38 g/cm3 and in Acuros it was forced to 8.0 g/cm3 (limited to selecting stainless steel). Three different relative electron densities (RED) were tested for each algorithm; 4.97, 6.97, and 8.97. Results: PDDs from both Acuros and AAA underestimated the delivered dose. AAA calculated that depth dose was higher for RED of 4.97 as compared to 6.97 and 8.97 but still lower than measured. There was no change in the percent depth dose with changing relative electron densities for Acuros. Conclusion: Care should be taken before using AAA or Acuros with cerrobend blocks as the planning system underestimates dose. Acuros limits the ability to modify RED when compared to AAA.« less

Associations of Diabetes and Obesity with Risk of Abdominal Aortic Aneurysm in Men

PubMed Central

Djousse, Luc; Song, Yiqing; Akinkuolie, Akintunde O.; Matsumoto, Chisa; Manson, JoAnn E.; Gaziano, J. Michael; Sesso, Howard D.

2017-01-01

Background. The associations of diabetes and obesity with the risk of abdominal aortic aneurysm (AAA) are inconclusive in previous studies. Subjects/Methods. We conducted prospective analysis in the Physicians' Health Study. Among 25,554 male physicians aged ≥ 50 years who reported no AAA at baseline, 471 reported a newly diagnosed AAA during a mean of 10.4 years' follow-up. Results. Compared with men who had baseline body mass index (BMI) < 25 kg/m2, the multivariable hazard ratio (HR [95% CI]) of newly diagnosed AAA was 1.30 [1.06–1.59] for BMI 25–<30 kg/m2 and 1.69 [1.24–2.30] for BMI ≥ 30 kg/m2. The risk of diagnosed AAA was significantly higher by 6% with each unit increase in baseline BMI. This association was consistent regardless of the other known AAA risk factors and preexisting vascular diseases. Overall, baseline history of diabetes tended to be associated with a lower risk of diagnosed AAA (HR = 0.79 [0.57–1.11]); this association appeared to vary by follow-up time (HR = 1.56 and 0.63 during ≤ and >2 years' follow-up, resp.). Conclusion. In a large cohort of middle-aged and older men, obesity was associated with a higher risk, while history of diabetes tended to associate with a lower risk of diagnosed AAA, particularly over longer follow-up. PMID:28326193

Identification and classification of genes required for tolerance to freeze-thaw stress revealed by genome-wide screening of Saccharomyces cerevisiae deletion strains.

PubMed

Ando, Akira; Nakamura, Toshihide; Murata, Yoshinori; Takagi, Hiroshi; Shima, Jun

2007-03-01

Yeasts used in bread making are exposed to freeze-thaw stress during frozen-dough baking. To clarify the genes required for freeze-thaw tolerance, genome-wide screening was performed using the complete deletion strain collection of diploid Saccharomyces cerevisiae. The screening identified 58 gene deletions that conferred freeze-thaw sensitivity. These genes were then classified based on their cellular function and on the localization of their products. The results showed that the genes required for freeze-thaw tolerance were frequently involved in vacuole functions and cell wall biogenesis. The highest numbers of gene products were components of vacuolar H(+)-ATPase. Next, the cross-sensitivity of the freeze-thaw-sensitive mutants to oxidative stress and to cell wall stress was studied; both of these are environmental stresses closely related to freeze-thaw stress. The results showed that defects in the functions of vacuolar H(+)-ATPase conferred sensitivity to oxidative stress and to cell wall stress. In contrast, defects in gene products involved in cell wall assembly conferred sensitivity to cell wall stress but not to oxidative stress. Our results suggest the presence of at least two different mechanisms of freeze-thaw injury: oxidative stress generated during the freeze-thaw process, and defects in cell wall assembly.

Numerical simulation of the stress distribution in a coal mine caused by a normal fault

NASA Astrophysics Data System (ADS)

Zhang, Hongmei; Wu, Jiwen; Zhai, Xiaorong

2017-06-01

Luling coal mine was used for research using FLAC3D software to analyze the stress distribution characteristics of the two sides of a normal fault zone with two different working face models. The working faces were, respectively, on the hanging wall and the foot wall; the two directions of mining were directed to the fault. The stress distributions were different across the fault. The stress was concentrated and the influenced range of stress was gradually larger while the working face was located on the hanging wall. The fault zone played a negative effect to the stress transmission. Obviously, the fault prevented stress transmission, the stress concentrated on the fault zone and the hanging wall. In the second model, the stress on the two sides decreased at first, but then increased continuing to transmit to the hanging wall. The concentrated stress in the fault zone decreased and the stress transmission was obvious. Because of this, the result could be used to minimize roadway damage and lengthen the time available for coal mining by careful design of the roadway and working face.

Wall shear stress in intracranial aneurysms and adjacent arteries☆

PubMed Central

Wang, Fuyu; Xu, Bainan; Sun, Zhenghui; Wu, Chen; Zhang, Xiaojun

2013-01-01

Hemodynamic parameters play an important role in aneurysm formation and growth. However, it is difficult to directly observe a rapidly growing de novo aneurysm in a patient. To investigate possible associations between hemodynamic parameters and the formation and growth of intracranial aneurysms, the present study constructed a computational model of a case with an internal carotid artery aneurysm and an anterior communicating artery aneurysm, based on the CT angiography findings of a patient. To simulate the formation of the anterior communicating artery aneurysm and the growth of the internal carotid artery aneurysm, we then constructed a model that virtually removed the anterior communicating artery aneurysm, and a further two models that also progressively decreased the size of the internal carotid artery aneurysm. Computational simulations of the fluid dynamics of the four models were performed under pulsatile flow conditions, and wall shear stress was compared among the different models. In the three aneurysm growth models, increasing size of the aneurysm was associated with an increased area of low wall shear stress, a significant decrease in wall shear stress at the dome of the aneurysm, and a significant change in the wall shear stress of the parent artery. The wall shear stress of the anterior communicating artery remained low, and was significantly lower than the wall shear stress at the bifurcation of the internal carotid artery or the bifurcation of the middle cerebral artery. After formation of the anterior communicating artery aneurysm, the wall shear stress at the dome of the internal carotid artery aneurysm increased significantly, and the wall shear stress in the upstream arteries also changed significantly. These findings indicate that low wall shear stress may be associated with the initiation and growth of aneurysms, and that aneurysm formation and growth may influence hemodynamic parameters in the local and adjacent arteries. PMID:25206394

Determination of wall shear stress from mean velocity and Reynolds shear stress profiles

NASA Astrophysics Data System (ADS)

Volino, Ralph J.; Schultz, Michael P.

2018-03-01

An analytical method is presented for determining the Reynolds shear stress profile in steady, two-dimensional wall-bounded flows using the mean streamwise velocity. The method is then utilized with experimental data to determine the local wall shear stress. The procedure is applicable to flows on smooth and rough surfaces with arbitrary pressure gradients. It is based on the streamwise component of the boundary layer momentum equation, which is transformed into inner coordinates. The method requires velocity profiles from at least two streamwise locations, but the formulation of the momentum equation reduces the dependence on streamwise gradients. The method is verified through application to laminar flow solutions and turbulent DNS results from both zero and nonzero pressure gradient boundary layers. With strong favorable pressure gradients, the method is shown to be accurate for finding the wall shear stress in cases where the Clauser fit technique loses accuracy. The method is then applied to experimental data from the literature from zero pressure gradient studies on smooth and rough walls, and favorable and adverse pressure gradient cases on smooth walls. Data from very near the wall are not required for determination of the wall shear stress. Wall friction velocities obtained using the present method agree with those determined in the original studies, typically to within 2%.

Abdominal aortic aneurysm: An update

PubMed

Chuen, Jason; Theivendran, Mayo

2018-05-01

Abdominal aortic aneurysm (AAA) remains one of the hallmark pathologies in vascular surgery and an area of intense research interest. Treatment options have expanded in recent years to increase the range of morphology suitable for endovascular aneurysm repair (EVAR), and with potential implications on treatment thresholds. This article is the first of two that will outline current treatment options for AAA, including areas of controversy and research in AAA disease, to inform the development of Australasian clinical guidelines and health policy. Medical therapy options remain limited and no aneurysm-specific pharmacotherapy is currently available. Recent years have witnessed a significant shift in AAA surgery from open repair to EVAR and expansion of EVAR techniques. General management of cardiovascular risk factors remains key to reducing all-cause mortality for patients with AAA.

Porphyromonas gingivalis Participates in Pathogenesis of Human Abdominal Aortic Aneurysm by Neutrophil Activation. Proof of Concept in Rats

PubMed Central

Delbosc, Sandrine; Alsac, Jean-Marc; Journe, Clement; Louedec, Liliane; Castier, Yves; Bonnaure-Mallet, Martine; Ruimy, Raymond; Rossignol, Patrick; Bouchard, Philippe; Michel, Jean-Baptiste; Meilhac, Olivier

2011-01-01

Background Abdominal Aortic Aneurysms (AAAs) represent a particular form of atherothrombosis where neutrophil proteolytic activity plays a major role. We postulated that neutrophil recruitment and activation participating in AAA growth may originate in part from repeated episodes of periodontal bacteremia. Methods and Findings Our results show that neutrophil activation in human AAA was associated with Neutrophil Extracellular Trap (NET) formation in the IntraLuminal Thrombus, leading to the release of cell-free DNA. Human AAA samples were shown to contain bacterial DNA with high frequency (11/16), and in particular that of Porphyromonas gingivalis (Pg), the most prevalent pathogen involved in chronic periodontitis, a common form of periodontal disease. Both DNA reflecting the presence of NETs and antibodies to Pg were found to be increased in plasma of patients with AAA. Using a rat model of AAA, we demonstrated that repeated injection of Pg fostered aneurysm development, associated with pathological characteristics similar to those observed in humans, such as the persistence of a neutrophil-rich luminal thrombus, not observed in saline-injected rats in which a healing process was observed. Conclusions Thus, the control of periodontal disease may represent a therapeutic target to limit human AAA progression. PMID:21533243

Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci

PubMed Central

Tromp, Gerard; Kuivaniemi, Helena; Gretarsdottir, Solveig; Baas, Annette F.; Giusti, Betti; Strauss, Ewa; van‘t Hof, Femke N.G.; Webb, Thomas R.; Erdman, Robert; Ritchie, Marylyn D.; Elmore, James R.; Verma, Anurag; Pendergrass, Sarah; Kullo, Iftikhar J.; Ye, Zi; Peissig, Peggy L.; Gottesman, Omri; Verma, Shefali S.; Malinowski, Jennifer; Rasmussen-Torvik, Laura J.; Borthwick, Kenneth M.; Smelser, Diane T.; Crosslin, David R.; de Andrade, Mariza; Ryer, Evan J.; McCarty, Catherine A.; Böttinger, Erwin P.; Pacheco, Jennifer A.; Crawford, Dana C.; Carrell, David S.; Gerhard, Glenn S.; Franklin, David P.; Carey, David J.; Phillips, Victoria L.; Williams, Michael J.A.; Wei, Wenhua; Blair, Ross; Hill, Andrew A.; Vasudevan, Thodor M.; Lewis, David R.; Thomson, Ian A.; Krysa, Jo; Hill, Geraldine B.; Roake, Justin; Merriman, Tony R.; Oszkinis, Grzegorz; Galora, Silvia; Saracini, Claudia; Abbate, Rosanna; Pulli, Raffaele; Pratesi, Carlo; Saratzis, Athanasios; Verissimo, Ana R.; Bumpstead, Suzannah; Badger, Stephen A.; Clough, Rachel E.; Cockerill, Gillian; Hafez, Hany; Scott, D. Julian A.; Futers, T. Simon; Romaine, Simon P.R.; Bridge, Katherine; Griffin, Kathryn J.; Bailey, Marc A.; Smith, Alberto; Thompson, Matthew M.; van Bockxmeer, Frank M.; Matthiasson, Stefan E.; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Blankensteijn, Jan D.; Teijink, Joep A.W.; Wijmenga, Cisca; de Graaf, Jacqueline; Kiemeney, Lambertus A.; Lindholt, Jes S.; Hughes, Anne; Bradley, Declan T.; Stirrups, Kathleen; Golledge, Jonathan; Norman, Paul E.; Powell, Janet T.; Humphries, Steve E.; Hamby, Stephen E.; Goodall, Alison H.; Nelson, Christopher P.; Sakalihasan, Natzi; Courtois, Audrey; Ferrell, Robert E.; Eriksson, Per; Folkersen, Lasse; Franco-Cereceda, Anders; Eicher, John D.; Johnson, Andrew D.; Betsholtz, Christer; Ruusalepp, Arno; Franzén, Oscar; Schadt, Eric E.; Björkegren, Johan L.M.; Lipovich, Leonard; Drolet, Anne M.; Verhoeven, Eric L.; Zeebregts, Clark J.; Geelkerken, Robert H.; van Sambeek, Marc R.; van Sterkenburg, Steven M.; de Vries, Jean-Paul; Stefansson, Kari; Thompson, John R.; de Bakker, Paul I.W.; Deloukas, Panos; Sayers, Robert D.; Harrison, Seamus C.; van Rij, Andre M.; Samani, Nilesh J.

2017-01-01

Rationale: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. Objective: To identify additional AAA risk loci using data from all available genome-wide association studies. Methods and Results: Through a meta-analysis of 6 genome-wide association study data sets and a validation study totaling 10 204 cases and 107 766 controls, we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches, we observed no new associations between the lead AAA single nucleotide polymorphisms and coronary artery disease, blood pressure, lipids, or diabetes mellitus. Network analyses identified ERG, IL6R, and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. Conclusions: The 4 new risk loci for AAA seem to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease. PMID:27899403

Beneficial Effects of Pre-operative Exercise Therapy in Patients with an Abdominal Aortic Aneurysm: A Systematic Review.

PubMed

Pouwels, S; Willigendael, E M; van Sambeek, M R H M; Nienhuijs, S W; Cuypers, P W M; Teijink, J A W

2015-01-01

The impact of post-operative complications in abdominal aortic aneurysm (AAA) surgery is substantial, and increases with age and concomitant co-morbidities. This systematic review focuses on the possible effects of pre-operative exercise therapy (PET) in patients with AAA on post-operative complications,aerobic capacity, physical fitness, and recovery. A systematic search on PET prior to AAA surgery was conducted. The methodological quality of the included studies was rated using the Physiotherapy Evidence Database scale. The agreement between the reviewers was assessed with Cohen's kappa. Five studies were included, with a methodological quality ranging from moderate to good. Cohen's kappa was 0.79. Three studies focused on patients with an AAA (without indication for surgical repair) with physical fitness as the outcome measure. One study focused on PET in patients awaiting AAA surgery and one study focused on the effects of PET on post-operative complications, length of stay, and recovery. PET has beneficial effects on various physical fitness variables of patients with an AAA. Whether this leads to less complications or faster recovery remains unclear. In view of the large impact of post-operative complications, it is valuable to explore the possible benefits of a PET program in AAA surgery.

Hyperhomocysteinaemia is an independent risk factor of abdominal aortic aneurysm in a Chinese Han population

PubMed Central

Liu, Jie; Wei Zuo, Shang; Li, Yue; Jia, Xin; Jia, Sen Hao; Zhang, Tao; Xiang Song, Yu; Qi Wei, Ying; Xiong, Jiang; Hua Hu, Yong; Guo, Wei

2016-01-01

The associations between hyperhomocysteinaemia (HHcy), methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, and abdominal aortic aneurysm (AAA) remain controversial, with only few studies focused on these associations within the Chinese population. We performed subgroup and interaction analyses in a Chinese Han population to investigate these associations. In all, 155 AAA patients and 310 control subjects were evaluated for serum total homocysteine levels and MTHFR C677T polymorphisms. Multiple logistic regression models were used to evaluate the aforementioned associations. Interaction and stratified analyses were conducted according to age, sex, smoking status, drinking status, and chronic disease histories. The multiple logistic analyses showed a significant association between HHcy and AAA but no significant association between MTHFR C677T polymorphism and AAA. The interaction analysis showed that age and peripheral arterial disease played an interactive role in the association between HHcy and AAA, while drinking status played an interactive role in the association between MTHFR C677T polymorphism and AAA. In conclusion, HHcy is an independent risk factor of AAA in a Chinese Han population, especially in the elderly and peripheral arterial disease subgroups. Longitudinal studies and clinical trials aimed to reduce homocysteine levels are warranted to assess the causal nature of these relationships PMID:26865327

Preclinical Evaluation of RYM1, a Matrix Metalloproteinase-Targeted Tracer for Imaging Aneurysm.

PubMed

Toczek, Jakub; Ye, Yunpeng; Gona, Kiran; Kim, Hye-Yeong; Han, Jinah; Razavian, Mahmoud; Golestani, Reza; Zhang, Jiasheng; Wu, Terence L; Jung, Jae-Joon; Sadeghi, Mehran M

2017-08-01

Matrix metalloproteinases (MMPs) play a key role in abdominal aortic aneurysm (AAA) development. Accordingly, MMP-targeted imaging provides important information regarding vessel wall biology in the course of aneurysm development. Given the small size of the vessel wall and its proximity with blood, molecular imaging of aneurysm optimally requires highly sensitive tracers with rapid blood clearance. To this end, we developed a novel hydrosoluble zwitterionic MMP inhibitor, RYM, on the basis of which a pan-MMP tracer, RYM1, was designed. Here, we describe the development and preclinical evaluation of RYM1 in comparison with RP805, a commonly used pan-MMP tracer in murine models of aneurysm. Methods: The macrocyclic hydroxamate-based pan-MMP inhibitor coupled with 6-hydrazinonicotinamide, RYM1, was synthesized and labeled with 99m Tc. Radiochemical stability of 99m Tc-RYM1 was evaluated by radio-high-performance liquid chromatography analysis. Tracer blood kinetics and biodistribution were compared with 99m Tc-RP805 in C57BL/6J mice ( n = 10). 99m Tc-RYM1 binding to aneurysm and specificity were evaluated by quantitative autoradiography in apolipoprotein E-deficient (apoE -/- ) mice with CaCl 2 -induced carotid aneurysm ( n = 11). Angiotensin II-infused apoE -/- ( n = 16) mice were used for small-animal SPECT/CT imaging. Aortic tissue MMP activity and macrophage marker CD68 expression were assessed by zymography and reverse-transcription polymerase chain reaction. Results: RYM1 showed nanomolar range inhibition constants for several MMPs. 99m Tc-RYM1 was radiochemically stable in mouse blood for 5 h and demonstrated rapid renal clearance and lower blood levels in vivo compared with 99m Tc-RP805. 99m Tc-RYM1 binding to aneurysm and its specificity were shown by autoradiography in carotid aneurysm. Angiotensin II infusion in apoE -/- mice for 4 wk resulted in AAA formation in 36% (4/11) of surviving animals. In vivo 99m Tc-RYM1 small-animal SPECT/CT images showed higher uptake of the tracer in AAA than nondilated aortae. Finally, aortic uptake of 99m Tc-RYM1 in vivo correlated with aortic MMP activity and CD68 expression. Conclusion: The newly developed pan-MMP inhibitor-based tracer 99m Tc-RYM1 displays favorable pharmacokinetics for early vascular imaging and enables specific detection of inflammation and MMP activity in aneurysm. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

NASA Airborne Astronomy Ambassadors (AAA)

NASA Astrophysics Data System (ADS)

Backman, D. E.; Harman, P. K.; Clark, C.

2016-12-01

NASA's Airborne Astronomy Ambassadors (AAA) is a three-part professional development (PD) program for high school physics and astronomy teachers. The AAA experience consists of: (1) blended-learning professional development composed of webinars, asynchronous content learning, and a series of hands-on workshops (2) a STEM immersion experience at NASA Armstrong Flight Research Center's B703 science research aircraft facility in Palmdale, California, and (3) ongoing participation in the AAA community of practice (CoP) connecting participants with astrophysics and planetary science Subject Matter Experts (SMEs). The SETI Institute (SI) is partnering with school districts in Santa Clara and Los Angeles Counties during the AAA program's "incubation" period, calendar years 2016 through 2018. AAAs will be selected by the school districts based on criteria developed during spring 2016 focus group meetings led by the program's external evaluator, WestEd.. Teachers with 3+ years teaching experience who are assigned to teach at least 2 sections in any combination of the high school courses Physics (non-AP), Physics of the Universe (California integrated model), Astronomy, or Earth & Space Sciences are eligible. Partner districts will select at least 48 eligible applicants with SI oversight. WestEd will randomly assign selected AAAs to group A or group B. Group A will complete PD in January - June of 2017 and then participate in SOFIA science flights during fall 2017 (SOFIA Cycle 5). Group B will act as a control during the 2017-18 school year. Group B will then complete PD in January - June of 2018 and participate in SOFIA science flights in fall 2018 (Cycle 6). Under the current plan, opportunities for additional districts to seek AAA partnerships with SI will be offered in 2018 or 2019. A nominal two-week AAA curriculum component will be developed by SI for classroom delivery that will be aligned with selected California Draft Science Framework Disciplinary Core Ideas, Crosscutting Concepts, and Science and Engineering Practices. (The California Draft Framework in turn is aligned with NGSS). The AAA program will demonstrate student gains in standards-based student learning, measure changes in student attitudes towards STEM, and observe & record Ambassadors' implementation of curricular changes.

Diabetes mellitus increases the risk of ruptured abdominal aortic aneurysms.

PubMed

Wierzba, Waldemar; Sliwczynski, Andrzej; Pinkas, Jaroslaw; Jawien, Arkadiusz; Karnafel, Waldemar

2017-09-01

The publication is a polemical response to reports that present data that diabetes reduces the risk of rupture of abdominal aortic aneurysm (AAA). The study analyzed all cases of developing AAA in patients with and without diabetes in 2012 in Poland. Data for the analysis were obtained with a unique and complete resources of the National Health Fund (NFZ) and population data from the Central Statistical Office (GUS). In Poland during 2012 2,227,453 patients with diabetes were treated, 975,364 males and 1,252,089 females. The incidence of AAA without rupture in patients without diabetes calculated per 100,000 of the non-diabetes general population was 25.0 +/- 9.0 in males and 5.6 +/- 2.3 in females. The incidence of ruptured AAA in the general population without diabetes was 3.6 +/- 0.9 in males, and 0.6 +/- 0.3 in females calculated per 100,000 of inhabitants without diabetes. The incidence of AAA without rupture in patients with diabetes was 184.897 +/- 70.653 in males and 35.364 +/- 24.925 in females calculated per 100,000 of patients diagnosed with diabetes. The incidence of ruptured AAA in patients with diabetes was 21.090 +/- 6.050 in males and 5.170 +/- 3.053 in females calculated per 100,000 of patients diagnosed with diabetes. The incidence rate for ruptured AAA in 2012 in Poland is statistically higher both in females and males in the population with diabetes. The incidence rate for AAA without rupture in 2012 in Poland is statistically higher in patients diagnosed with diabetes.

Low Serum Levels of EPA are Associated with the Size and Growth Rate of Abdominal Aortic Aneurysm.

PubMed

Aikawa, Tatsuro; Miyazaki, Tetsuro; Shimada, Kazunori; Sugita, Yurina; Shimizu, Megumi; Ouchi, Shohei; Kadoguchi, Tomoyasu; Yokoyama, Yasutaka; Shiozawa, Tomoyuki; Hiki, Masaru; Takahashi, Shuhei; Al Shahi, Hamad; Dohi, Shizuyuki; Amano, Atsushi; Daida, Hiroyuki

2017-09-01

Omega-3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been reported to reduce the risk of cardiovascular disease. However, whether omega-3 PUFAs are involved in the pathogenesis of abdominal aortic aneurysms (AAA) remains unclear. We analyzed 67 consecutive patients admitted for the elective surgical repair of AAA. We investigated the association of serum EPA and DHA levels as well as the EPA/AA ratio with the size of AAA assessed using three-dimensional reconstructed computed tomography images. Mean patient age was 70±9 years and 60 patients were male. Serum EPA and DHA levels were 75.2±35.7 μg/mL and 146.1±48.5 μg/mL, respectively. EPA/AA ratio was 0.44±0.22, which was lower than those in healthy Japanese subject and equivalent to those in Japanese patients with coronary artery disease as previously reported. Mean of the maximum AAA diameter was 56.4±8.9 mm, and serum EPA levels and EPA/AA ratio negatively correlated with it (r=-0.32 and r=-0.32, respectively). Multiple liner regression analysis showed that EPA levels were significant independent factor contributing to the maximum AAA diameter. Furthermore, low serum EPA levels and low EPA/AA ratio were significantly associated with the growth rate of AAA diameter (r=-0.43 and r=-0.33, respectively). EPA levels in patients with AAA were relatively low. Low serum EPA levels and EPA/AA ratio were associated with the size and growth rate of AAA.

Functional characterization of T cells in abdominal aortic aneurysms

PubMed Central

Forester, Nerys D; Cruickshank, Sheena M; Scott, D Julian A; Carding, Simon R

2005-01-01

Abdominal aortic aneurysms (AAA) exhibit features of a chronic inflammatory disorder. The functional attributes of the T cells in AAA tissue are unclear, with little quantitative or functional data. Using a novel, non-enzymatic method to isolate viable cells from AAA tissue, functional properties of AAA T cells were investigated for the first time. Composition and phenotype of AAA T cells was determined by flow cytometry and verified by immunohistochemistry. Tissue mononuclear cells (MNCs) were cultured in the presence of T-cell mitogens, and cell cycle analysis and cytokine production assessed. Typical cell yield was 4·5 × 106 cells per gram of AAA tissue. The majority (58·1 ± 5·3%) of haematopoietic (CD45+) cells recovered were CD3+ T cells, B cells comprised 41·1 ± 5·7%, natural killer cells 7·3 ± 2·5%, and macrophages 2%. Freshly isolated T cells were in resting (G1) state, with 25% expressing the activation-associated cell surface antigens major histocompatibility complex II and CD25. When stimulated in vitro, a significant proportion entered S and G2 phase of the cell cycle, up-regulated CD25, and secreted tumour necrosis factor-α, interferon-γ, interleukin (IL)-5 and IL-6. Despite patient differences, the composition of the AAA inflammatory infiltrate was remarkably consistent, and when re-stimulated ex-vivo T cells produced a stereotypical cytokine response, consistent with the hypothesis that AAA T cells can promote tissue inflammation by secretion of proinflammatory cytokines, and in addition provide signals for B-cell help. PMID:15885133

Atmospheric Pressure and Abdominal Aortic Aneurysm Rupture: Results From a Time Series Analysis and Case-Crossover Study.

PubMed

Penning de Vries, Bas B L; Kolkert, Joé L P; Meerwaldt, Robbert; Groenwold, Rolf H H

2017-10-01

Associations between atmospheric pressure and abdominal aortic aneurysm (AAA) rupture risk have been reported, but empirical evidence is inconclusive and largely derived from studies that did not account for possible nonlinearity, seasonality, and confounding by temperature. Associations between atmospheric pressure and AAA rupture risk were investigated using local meteorological data and a case series of 358 patients admitted to hospital for ruptured AAA during the study period, January 2002 to December 2012. Two analyses were performed-a time series analysis and a case-crossover study. Results from the 2 analyses were similar; neither the time series analysis nor the case-crossover study showed a significant association between atmospheric pressure ( P = .627 and P = .625, respectively, for mean daily atmospheric pressure) or atmospheric pressure variation ( P = .464 and P = .816, respectively, for 24-hour change in mean daily atmospheric pressure) and AAA rupture risk. This study failed to support claims that atmospheric pressure causally affects AAA rupture risk. In interpreting our results, one should be aware that the range of atmospheric pressure observed in this study is not representative of the atmospheric pressure to which patients with AAA may be exposed, for example, during air travel or travel to high altitudes in the mountains. Making firm claims regarding these conditions in relation to AAA rupture risk is difficult at best. Furthermore, despite the fact that we used one of the largest case series to date to investigate the effect of atmospheric pressure on AAA rupture risk, it is possible that this study is simply too small to demonstrate a causal link.

Animal-assisted activity and emotional status of patients with Alzheimer's disease in day care.

PubMed

Mossello, Enrico; Ridolfi, Alessandro; Mello, Anna Maria; Lorenzini, Giulia; Mugnai, Francesca; Piccini, Carolina; Barone, Domenico; Peruzzi, Anna; Masotti, Giulio; Marchionni, Niccolò

2011-08-01

Preliminary studies suggest beneficial effects of animal-assisted activities (AAA) on behavioral and psychological symptoms of dementia (BPSD), but data are inconsistent. This study aimed to assess the effect of AAA with dogs on cognition, BPSD, emotional status and motor activity in severe Alzheimer's disease (AD). Ten patients attending an Alzheimer Day Care Center (ADCC) participated in a repeated measures study, which included: two weeks' pre-intervention, three weeks' control activity with plush dogs (CA), and three weeks' AAA. Cognitive function (Severe Impairment Battery), mood (Cornell Scale for Depression in Dementia; CSDD), BPSD (Neuropsychiatric Inventory; NPI) and agitation (Cohen-Mansfield Agitation Inventory; CMAI) were assessed at baseline and after each period. Observed Emotion Rating Scale (OERS) for emotional status, Agitated Behavior Mapping Instrument (ABMI) and a checklist for motor activity were completed across the study periods, both during intervention sessions and after three hours. Cognition and NPI were unchanged across the study. Declines in the CMAI and CSDD scores after AAA were not significant, while the NPI anxiety item score decreased in comparison with CA (CA 3.1±2.3, AAA 1.5±2.7, p = 0.04). OERS "sadness" decreased (p = 0.002), while "pleasure" (p = 0.016) and "general alertness" (p = 0.003) increased during AAA compared with CA sessions, and observed sadness remained lower after three hours (p = 0.002). Motor activity increased significantly during AAA. In this sample of severe AD patients in ADCC, AAA was associated with a decrease in anxiety and sadness and an increase in positive emotions and motor activity in comparison with a control activity.

Characterization of the binding specificity of Anguilla anguilla agglutinin (AAA) in comparison to Ulex europaeus agglutinin I (UEA-I).

PubMed

Baldus, S E; Thiele, J; Park, Y O; Hanisch, F G; Bara, J; Fischer, R

1996-08-01

Using immunochemical and immunohistochemical methods, the binding site of Anguilla anguilla agglutinin (AAA) was characterized and compared with the related fucose-specific lectin from Ulex europaeus (UEA-I). In solid-phase enzyme-linked immunoassays, the two lectins recognized Fuc alpha 1-2Gal beta-HSA. AAA additionally cross-reacted with neoglycolipids bearing lacto-N-fucopentaose (LNFP) I [H type 1] and II [Le(a)] and lactodifucotetraose (LDFT) as glycan moieties. UEA-I, on the other hand, bound to a LDFT-derived neoglycolipid but not to the other neoglycolipids tested. Binding of AAA to gastric mucin was competitively neutralized by Le(a)-specific monoclonal antibodies. UEA-I binding, on the other hand, was reduced after co-incubation with H type 2- and Le(y)-specific monoclonal antibodies. According to our results, AAA reacts with fucosylated type 1 chain antigens, whereas UEA-I binds only to the alpha 1-2-fucosylated LDFT-derived neoglycolipid. In immunohistochemical studies, the reactivity of AAA and UEA-I in normal pyloric mucosa from individuals with known Lewis and secretor status was analysed. AAA showed a broad reaction in the superficial pyloric mucosa from secretors and non-secretors, but AAA reactivity was more pronounced in Le(a+b-) individuals. On the other hand, UEA-I stained the superficial pyloric mucosa only from secretor individuals. A staining of deep mucous glands by the lectins was found in all specimens. Both reacted with most human carcinomas of different origin. Slight differences in their binding pattern were observed and may be explained by the different fine-specificities of the lectins.

Molecular insights into the m-AAA protease-mediated dislocation of transmembrane helices in the mitochondrial inner membrane.

PubMed

Lee, Seoeun; Lee, Hunsang; Yoo, Suji; Kim, Hyun

2017-12-08

Protein complexes involved in respiration, ATP synthesis, and protein import reside in the mitochondrial inner membrane; thus, proper regulation of these proteins is essential for cell viability. The m -AAA protease, a conserved hetero-hexameric AAA (ATPase associated with diverse cellular activities) protease, composed of the Yta10 and Yta12 proteins, regulates mitochondrial proteostasis by mediating protein maturation and degradation. It also recognizes and mediates the dislocation of membrane-embedded substrates, including foreign transmembrane (TM) segments, but the molecular mechanism involved in these processes remains elusive. This study investigated the role of the TM domains in the m -AAA protease by systematic replacement of one TM domain at a time in yeast. Our data indicated that replacement of the Yta10 TM2 domain abolishes membrane dislocation for only a subset of substrates, whereas replacement of the Yta12 TM2 domain impairs membrane dislocation for all tested substrates, suggesting different roles of the TM domains in each m -AAA protease subunit. Furthermore, m -AAA protease-mediated membrane dislocation was impaired in the presence of a large downstream hydrophilic moiety in a membrane substrate. This finding suggested that the m -AAA protease cannot dislocate large hydrophilic domains across the membrane, indicating that the membrane dislocation probably occurs in a lipid environment. In summary, this study highlights previously underappreciated biological roles of TM domains of the m -AAA proteases in mediating the recognition and dislocation of membrane-embedded substrates. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Salt stress causes cell wall damage in yeast cells lacking mitochondrial DNA.

PubMed

Gao, Qiuqiang; Liou, Liang-Chun; Ren, Qun; Bao, Xiaoming; Zhang, Zhaojie

2014-03-03

The yeast cell wall plays an important role in maintaining cell morphology, cell integrity and response to environmental stresses. Here, we report that salt stress causes cell wall damage in yeast cells lacking mitochondrial DNA (ρ 0 ). Upon salt treatment, the cell wall is thickened, broken and becomes more sensitive to the cell wall-perturbing agent sodium dodecyl sulfate (SDS). Also, SCW11 mRNA levels are elevated in ρ 0 cells. Deletion of SCW11 significantly decreases the sensitivity of ρ 0 cells to SDS after salt treatment, while overexpression of SCW11 results in higher sensitivity. In addition, salt stress in ρ 0 cells induces high levels of reactive oxygen species (ROS), which further damages the cell wall, causing cells to become more sensitive towards the cell wall-perturbing agent.

Thinner regions of intracranial aneurysm wall correlate with regions of higher wall shear stress: a 7.0 tesla MRI

PubMed Central

Blankena, Roos; Kleinloog, Rachel; Verweij, Bon H.; van Ooij, Pim; ten Haken, Bennie; Luijten, Peter R.; Rinkel, Gabriel J.E.; Zwanenburg, Jaco J.M.

2016-01-01

Purpose To develop a method for semi-quantitative wall thickness assessment on in vivo 7.0 tesla (7T) MRI images of intracranial aneurysms for studying the relation between apparent aneurysm wall thickness and wall shear stress. Materials and Methods Wall thickness was analyzed in 11 unruptured aneurysms in 9 patients, who underwent 7T MRI with a TSE based vessel wall sequence (0.8 mm isotropic resolution). A custom analysis program determined the in vivo aneurysm wall intensities, which were normalized to signal of nearby brain tissue and were used as measure for apparent wall thickness (AWT). Spatial wall thickness variation was determined as the interquartile range in AWT (the middle 50% of the AWT range). Wall shear stress was determined using phase contrast MRI (0.5 mm isotropic resolution). We performed visual and statistical comparisons (Pearson’s correlation) to study the relation between wall thickness and wall shear stress. Results 3D colored AWT maps of the aneurysms showed spatial AWT variation, which ranged from 0.07 to 0.53, with a mean variation of 0.22 (a variation of 1.0 roughly means a wall thickness variation of one voxel (0.8mm)). In all aneurysms, AWT was inversely related to WSS (mean correlation coefficient −0.35, P<0.05). Conclusions A method was developed to measure the wall thickness semi-quantitatively, using 7T MRI. An inverse correlation between wall shear stress and AWT was determined. In future studies, this non-invasive method can be used to assess spatial wall thickness variation in relation to pathophysiologic processes such as aneurysm growth and –rupture. PMID:26892986

77 FR 13608 - Proposed Data Collections Submitted for Public Comment and Recommendations

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-07

... Against AIDS (AAA) in 2009, a 5-year, multifaceted communication campaign consisting of several campaigns targeting various high-risk populations. The overall goals of AAA are to increase HIV/AIDS awareness and reduce HIV incidence in the United States. Each AAA campaign uses mass media and direct-to-consumer...

Advanced, Analytic, Automated (AAA) Measurement of Engagement during Learning

ERIC Educational Resources Information Center

D'Mello, Sidney; Dieterle, Ed; Duckworth, Angela

2017-01-01

It is generally acknowledged that engagement plays a critical role in learning. Unfortunately, the study of engagement has been stymied by a lack of valid and efficient measures. We introduce the advanced, analytic, and automated (AAA) approach to measure engagement at fine-grained temporal resolutions. The AAA measurement approach is grounded in…

Common iliac artery aneurysms in patients with abdominal aortic aneurysms.

PubMed

Armon, M P; Wenham, P W; Whitaker, S C; Gregson, R H; Hopkinson, B R

1998-03-01

To determine the incidence of common iliac artery (CIA) aneurysms in patients with abdominal aortic aneurysms (AAA) and to evaluate the relationship between AAA and CIA diameter. Spiral CT angiography was used to measure the maximum diameters of the abdominal aorta and the common iliac arteries of 215 patients with AAA. The median CIA diameter was 1.7 cm--significantly greater than the published mean of 1.25 (2 S.D. = 0.85-1.65) cm of an age-matched, non-vascular population. Thirty-four patients (16%) had unilateral and 26 patients (12%) bilateral CIA aneurysms > or = 2.4 cm diameter. Eight-six vessels (20%) were affected. Right CIA diameters were wider than left CIA diameters (p < 0.0001, Wilcoxon matched-pairs signed rank test). The correlation between AAA size and CIA diameter was weak. The AAA population has abnormally dilated common iliac arteries. In this population, common iliac artery aneurysms should be defined as those greater than 2.4 cm diameter. 20% of CIAs in patients with AAA are aneurysmal according to this definition.

AAA (2010) CAPD clinical practice guidelines: need for an update.

PubMed

DeBonis, David A

2017-09-01

Review and critique of the clinical value of the AAA CAPD guidance document in light of criteria for credible and useful guidance documents, as discussed by Field and Lohr. A qualitative review of the of the AAA CAPD guidelines using a framework by Field and Lohr to assess their relative value in supporting the assessment and management of CAPD referrals. Relevant literature available through electronic search tools and published texts were used along with the AAA CAPD guidance document and the chapter by Field and Lohr. The AAA document does not meet many of the key requirements discussed by Field and Lohr. It does not reflect the current literature, fails to help clinicians understand for whom auditory processing testing and intervention would be most useful, includes contradictory suggestions which reduce clarity and appears to avoid conclusions that might cast the CAPD construct in a negative light. It also does not include input from diverse affected groups. All of these reduce the document's credibility. The AAA CAPD guidance document will need to be updated and re-conceptualised in order to provide meaningful guidance for clinicians.

Epidemiology of abdominal aortic aneurysms in the Asian community.

PubMed

Spark, J I; Baker, J L; Vowden, P; Wilkinson, D

2001-03-01

Studies relating to the ethnic origin of patients with an abdominal aortic aneurysm (AAA) are few and are mainly concerned with the differences between black and white Americans. The purpose of this study was to determine whether the incidence of AAA among the Asian population of Bradford is different from that in the Caucasian population. A retrospective study of patients with an AAA was carried out between 1990 and 1997 using data collected by the Patient Administrative Service, personal databases of the vascular consultants and theatre records. Information about the ethnic composition of the population of Bradford was obtained from the 1991 national census. Demographic data, including ethnic origin and clinical details, were obtained from patient notes. Two hundred and thirty-three patients with an AAA were identified during the study interval. The Asian population comprised 14.0 per cent of the total population of Bradford. Twenty-eight AAAs would be expected per year. All of the aneurysms identified occurred in the Caucasian population and none in the Asian community. These early results suggest that AAA is rare among the Asian population.

Log-layer mismatch and modeling of the fluctuating wall stress in wall-modeled large-eddy simulations

NASA Astrophysics Data System (ADS)

Yang, Xiang I. A.; Park, George Ilhwan; Moin, Parviz

2017-10-01

Log-layer mismatch refers to a chronic problem found in wall-modeled large-eddy simulation (WMLES) or detached-eddy simulation, where the modeled wall-shear stress deviates from the true one by approximately 15 % . Many efforts have been made to resolve this mismatch. The often-used fixes, which are generally ad hoc, include modifying subgrid-scale stress models, adding a stochastic forcing, and moving the LES-wall-model matching location away from the wall. An analysis motivated by the integral wall-model formalism suggests that log-layer mismatch is resolved by the built-in physics-based temporal filtering. In this work we investigate in detail the effects of local filtering on log-layer mismatch. We show that both local temporal filtering and local wall-parallel filtering resolve log-layer mismatch without moving the LES-wall-model matching location away from the wall. Additionally, we look into the momentum balance in the near-wall region to provide an alternative explanation of how LLM occurs, which does not necessarily rely on the numerical-error argument. While filtering resolves log-layer mismatch, the quality of the wall-shear stress fluctuations predicted by WMLES does not improve with our remedy. The wall-shear stress fluctuations are highly underpredicted due to the implied use of LES filtering. However, good agreement can be found when the WMLES data are compared to the direct numerical simulation data filtered at the corresponding WMLES resolutions.

[Ultrasound screening of abdominal aortic aneurysm: Lessons from Vesale 2013].

PubMed

Laroche, J P; Becker, F; Baud, J M; Miserey, G; Jaussent, A; Picot, M C; Bura-Rivière, A; Quéré, I

2015-12-01

Although aneurysm of the abdominal infra-renal aorta (AAA) meets criteria warranting B mode ultrasound screening, the advantages of mass screening versus selective targeted opportunistic screening remain a subject of debate. In France, the French Society of Vascular Medicine (SFMV) and the Health Authority (HAS) published recommendations for targeted opportunistic screening in 2006 and 2013 respectively. The SFMV held a mainstream communication day on November 21, 2013 in France involving participants from metropolitan France and overseas departments that led to a proposal for free AAA ultrasound screening: the Vesalius operation. Being a consumer operation, the selection criteria were limited to age (men and women between 60 and 75 years); the age limit was lowered to 50 years in case of direct family history of AAA. More than 7000 people (as many women as men) were screened in 83 centers with a 1.70% prevalence of AAA in the age-based target population (3.12% for men, 0.27% for women). The median diameter of detected AAA was 33 mm (range 20 to 74 mm). The prevalence of AAA was 1.7% in this population. Vesalius data are consistent with those of the literature both in terms of prevalence and for cardiovascular risk factors with the important role of smoking. Lessons from Vesalius to take into consideration are: screening is warranted in men 60 years and over, especially smokers, and in female smokers. Screening beyond 75 years should be discussed. Given the importance of screening, the SFMV set up a year of national screening for AAA (Vesalius operation 2014/2015) in order to increase public and physician awareness about AAA detection, therapeutic management, and monitoring. AAA is a serious, common, disease that kills 6000 people each year. The goal of screening is cost-effective reduction in the death toll. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Human serum cholinesterase from liver pathological samples exhibit highly elevated aryl acylamidase activity.

PubMed

Boopathy, Rathanam; Rajesh, Ramanna Valmiki; Darvesh, Sultan; Layer, Paul G

2007-05-01

Although aspartate aminotransferase (AST) and gamma-glutamyltransferase (gamma GT) enzymes are widely used as markers for liver disorders, the ubiquitous enzyme butyrylcholinesterase (BChE), synthesized in liver is also used as marker in the assessment of liver pathophysiology. This BChE enzyme in addition to its esterase activity has yet another enzymatic function designated as aryl acylamidase (AAA) activity. It is determined in in vitro based on the hydrolysis of the synthetic substrate o-nitroacetanilide. In the present study, human serum cholinesterase (BChE) activity was studied with respect to its AAA activity on the BChE protein (AAA(BChE)) in patients with liver disorders. AST and gamma GT values were taken into account in this study as known markers for liver disorders. Blood samples were grouped into 3 based on esterase activity associated with BChE protein. They are normal, low, and very low BChE activity but with markedly increased AST and gamma GT levels. These samples were tested for their respective AAA function. Association of AAA with BChE from samples was proved using BChE monoclonal antibody precipitation experiment. The absolute levels of AAA were increased as BChE activity decreased while deviating from normal samples and such deviation was directly proportional to the severity of the liver disorder. Differences between these groups became prominent after determining the ratios of AAA(BChE) to BChE activities. Samples showing very high AAA(BChE) to BChE ratio were also showing high to very high gamma GT values. These findings establish AAA(BChE) as an independently regulated enzymatic activity on BChE especially in liver disorders. Moreover, since neither the low esterase activity of BChE by itself nor increased levels of AST/gamma GT are sufficient pathological indicators, this pilot study merits replication with large sample numbers.

Angiotensin-Induced Abdominal Aortic Aneurysms in Hypercholesterolemic Mice: Role of Serum Cholesterol and Temporal Effects of Exposure

PubMed Central

Prins, Petra A.; Hill, Michael F.; Airey, David; Nwosu, Sam; Perati, Prudhvidhar R.; Tavori, Hagai; F. Linton, MacRae; Kon, Valentina; Fazio, Sergio; Sampson, Uchechukwu K.

2014-01-01

Objective Understanding variations in size and pattern of development of angiotensin II (Ang II)-induced abdominal aortic aneurysms (AAA) may inform translational research strategies. Thus, we sought insight into the temporal evolution of AAA in apolipoprotein (apo)E−/− mice. Approach A cohort of mice underwent a 4-week pump-mediated infusion of saline (n = 23) or 1500 ng/kg/min of Ang II (n = 85) and AAA development was tracked via in vivo ultrasound imaging. We adjusted for hemodynamic covariates in the regression models for AAA occurrence in relation to time. Results The overall effect of time was statistically significant (p<0.001). Compared to day 7 of AngII infusion, there was no decrease in the log odds of AAA occurrence by day 14 (−0.234, p = 0.65), but compared to day 21 and 28, the log odds decreased by 9.07 (p<0.001) and 2.35 (p = 0.04), respectively. Hemodynamic parameters were not predictive of change in aortic diameter (Δ) (SBP, p = 0.66; DBP, p = 0.66). Mean total cholesterol (TC) was higher among mice with large versus small AAA (601 vs. 422 mg/ml, p<0.0001), and the difference was due to LDL. AngII exposure was associated with 0.43 mm (95% CI, 0.27 to 0.61, p<0.0001) increase in aortic diameter; and a 100 mg/dl increase in mean final cholesterol level was associated with a 12% (95% CI, 5.68 to 18.23, p<0.0001) increase in aortic diameter. Baseline cholesterol was not associated with change in aortic diameter (p = 0.86). Conclusions These are the first formal estimates of a consistent pattern of Ang II-induced AAA development. The odds of AAA occurrence diminish after the second week of Ang II infusion, and TC is independently associated with AAA size. PMID:24465413

Dosimetric comparison of peripheral NSCLC SBRT using Acuros XB and AAA calculation algorithms.

PubMed

Ong, Chloe C H; Ang, Khong Wei; Soh, Roger C X; Tin, Kah Ming; Yap, Jerome H H; Lee, James C L; Bragg, Christopher M

2017-01-01

There is a concern for dose calculation in highly heterogenous environments such as the thorax region. This study compares the quality of treatment plans of peripheral non-small cell lung cancer (NSCLC) stereotactic body radiation therapy (SBRT) using 2 calculation algorithms, namely, Eclipse Anisotropic Analytical Algorithm (AAA) and Acuros External Beam (AXB), for 3-dimensional conformal radiation therapy (3DCRT) and volumetric-modulated arc therapy (VMAT). Four-dimensional computed tomography (4DCT) data from 20 anonymized patients were studied using Varian Eclipse planning system, AXB, and AAA version 10.0.28. A 3DCRT plan and a VMAT plan were generated using AAA and AXB with constant plan parameters for each patient. The prescription and dose constraints were benchmarked against Radiation Therapy Oncology Group (RTOG) 0915 protocol. Planning parameters of the plan were compared statistically using Mann-Whitney U tests. Results showed that 3DCRT and VMAT plans have a lower target coverage up to 8% when calculated using AXB as compared with AAA. The conformity index (CI) for AXB plans was 4.7% lower than AAA plans, but was closer to unity, which indicated better target conformity. AXB produced plans with global maximum doses which were, on average, 2% hotter than AAA plans. Both 3DCRT and VMAT plans were able to achieve D95%. VMAT plans were shown to be more conformal (CI = 1.01) and were at least 3.2% and 1.5% lower in terms of PTV maximum and mean dose, respectively. There was no statistically significant difference for doses received by organs at risk (OARs) regardless of calculation algorithms and treatment techniques. In general, the difference in tissue modeling for AXB and AAA algorithm is responsible for the dose distribution between the AXB and the AAA algorithms. The AXB VMAT plans could be used to benefit patients receiving peripheral NSCLC SBRT. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

SU-E-T-538: Evaluation of IMRT Dose Calculation Based on Pencil-Beam and AAA Algorithms.

PubMed

Yuan, Y; Duan, J; Popple, R; Brezovich, I

2012-06-01

To evaluate the accuracy of dose calculation for intensity modulated radiation therapy (IMRT) based on Pencil Beam (PB) and Analytical Anisotropic Algorithm (AAA) computation algorithms. IMRT plans of twelve patients with different treatment sites, including head/neck, lung and pelvis, were investigated. For each patient, dose calculation with PB and AAA algorithms using dose grid sizes of 0.5 mm, 0.25 mm, and 0.125 mm, were compared with composite-beam ion chamber and film measurements in patient specific QA. Discrepancies between the calculation and the measurement were evaluated by percentage error for ion chamber dose and γ〉l failure rate in gamma analysis (3%/3mm) for film dosimetry. For 9 patients, ion chamber dose calculated with AAA-algorithms is closer to ion chamber measurement than that calculated with PB algorithm with grid size of 2.5 mm, though all calculated ion chamber doses are within 3% of the measurements. For head/neck patients and other patients with large treatment volumes, γ〉l failure rate is significantly reduced (within 5%) with AAA-based treatment planning compared to generally more than 10% with PB-based treatment planning (grid size=2.5 mm). For lung and brain cancer patients with medium and small treatment volumes, γ〉l failure rates are typically within 5% for both AAA and PB-based treatment planning (grid size=2.5 mm). For both PB and AAA-based treatment planning, improvements of dose calculation accuracy with finer dose grids were observed in film dosimetry of 11 patients and in ion chamber measurements for 3 patients. AAA-based treatment planning provides more accurate dose calculation for head/neck patients and other patients with large treatment volumes. Compared with film dosimetry, a γ〉l failure rate within 5% can be achieved for AAA-based treatment planning. © 2012 American Association of Physicists in Medicine.

Association of high sensitivity C-reactive protein and abdominal aortic aneurysm: a meta-analysis and systematic review.

PubMed

Wang, Yunpeng; Shen, Guanghui; Wang, Haiyang; Yao, Ye; Sun, Qingfeng; Jing, Bao; Liu, Gaoyan; Wu, Jia; Yuan, Chao; Liu, Siqi; Liu, Xinyu; Li, Shiyong; Li, Haocheng

2017-12-01

To evaluate the association of high sensitivity C-reactive protein (hsCRP) with the presence of abdominal aortic aneurysm (AAA). Medline, Cochrane, Embase, and Google Scholar databases were searched until 22 June 2016 using the keywords predictive factors, biomarkers, abdominal aortic aneurysm, prediction, high sensitivity C-reactive protein, and hsCRP. Prospective studies, retrospective studies, and cohort studies were included. Twelve case-control studies were included in the meta-analysis with a total of 8345 patients (1977 in the AAA group and 6368 in the control group). The pooled results showed that AAA patients had higher hsCRP value than the control group (difference in means = 1.827, 95% CI = 0.010 to 3.645, p = .049). Subgroup analysis found AAA patients with medium or small aortic diameter (<50 mm) had higher hsCRP plasma levels than the control group (difference in means = 1.301, 95% CI = 0.821 to 1.781, p < .001). In patients with large aortic diameter (≥50 mm), no difference was observed in hsCRP levels between the AAA and control groups (difference in means = 1.769, 95% CI = -1.387 to 4.925, p = .272). Multi-regression analysis found the difference in means of hsCRP plasma levels between AAA and control groups decreased as aortic diameter increased (slope = -0.04, p < .001), suggesting that hsCRP levels may be inversely associated with increasing aneurysm size. Our findings suggest that hsCRP levels may possibly be used as a diagnostic biomarker for AAA patients with medium or small aortic diameter but not for AAA patients with large aortic diameter. The correlation between serum hsCRP level and AAA aneurysm is not conclusive due to the small number of included articles and between-study heterogeneity.

Anatomic characteristics of ruptured abdominal aortic aneurysm on conventional CT scans: Implications for rupture risk.

PubMed

Fillinger, Mark F; Racusin, Jessica; Baker, Robert K; Cronenwett, Jack L; Teutelink, Arno; Schermerhorn, Marc L; Zwolak, Robert M; Powell, Richard J; Walsh, Daniel B; Rzucidlo, Eva M

2004-06-01

The purpose of this study was to analyze anatomic characteristics of patients with ruptured abdominal aortic aneurysms (AAAs), with conventional two-dimensional computed tomography (CT), including comparison with control subjects matched for age, gender, and size. Records were reviewed to identify all CT scans obtained at Dartmouth-Hitchcock Medical Center or referring hospitals before emergency AAA repair performed because of rupture or acute severe pain (RUP group). CT scans obtained before elective AAA repair (ELEC group) were reviewed for age and gender match with patients in the RUP group. More than 40 variables were measured on each CT scan. Aneurysm diameter matching was achieved by consecutively deleting the largest RUP scan and the smallest ELEC scan to prevent bias. CT scans were analyzed for 259 patients with AAAs: 122 RUP and 137 ELEC. Patients were well matched for age, gender, and other demographic variables or risk factors. Maximum AAA diameter was significantly different in comparisons of all patients (RUP, 6.5 +/- 2 cm vs ELEC, 5.6 +/- 1 cm; P <.0001), and mean diameter of ruptured AAAs was 5 mm smaller in female patients (6.1 +/- 2 cm vs 6.6 +/- 2 cm; P =.007). Two hundred patients were matched for diameter, gender, and age (100 from each group; maximum AAA diameter, 6.0 +/- 1 cm vs 6.0 +/- 1 cm). Analysis of diameter-matched AAAs indicated that most variables were statistically similar in the two groups, including infrarenal neck length (17 +/- 1 mm vs 19 +/- 1 mm; P =.3), maximum thrombus thickness (25 +/- 1 mm vs 23 +/- 1 mm, P =.4), and indices of body habitus, such as [(maximum AAA diameter)/(normal suprarenal aorta diameter)] or [(maximum AAA diameter)/(L3 transverse diameter)]. Multivariate analysis controlling for gender indicated that the most significant variables for rupture were aortic tortuosity (odds ratio [OR] 3.3, indicating greater risk with no or mild tortuosity), diameter asymmetry (OR, 3.2 for a 1-cm difference in major-minor axis), and current smoking (OR, 2.7, with the greater risk in current smokers). When matched for age, gender, and diameter, ruptured AAAs tend to be less tortuous, yet have greater cross-sectional diameter asymmetry. On conventional two-dimensional CT axial sections, it appears that when diameter asymmetry is associated with low aortic tortuosity, the larger diameter on axial sections more accurately reflects rupture risk, and when diameter asymmetry is associated with moderate or severe aortic tortuosity, the smaller diameter on axial sections more accurately reflects rupture risk. Current smoking is significantly associated with rupture, even when controlling for gender and AAA anatomy.

Selective Intra-procedural AAA sac Embolization During EVAR Reduces the Rate of Type II Endoleak.

PubMed

Mascoli, C; Freyrie, A; Gargiulo, M; Gallitto, E; Pini, R; Faggioli, G; Serra, C; De Molo, C; Stella, A

2016-05-01

The pre-treatment presence of at least six efferent patent vessels (EPV) from the AAA sac and/or AAA thrombus volume ratio (VR%) <40% are considered to be positive predictive factors for persistent type II endoleak (ELIIp). The aim of the present study was to evaluate the effectiveness of sac embolization during EVAR in patients with pre-operative morphological risk factors (p-MRF) for ELIIp. Patients undergoing EVAR and intra-procedural AAA sac embolization (Group A, 2012-2013) were retrospectively selected and compared with a control group of patients with the same p-MRF, who underwent EVAR without intra-procedural sac embolization (Group B, 2008-2010). The presence of ELIIp was evaluated by duplex ultrasound at 0 and 6 months, and by contrast enhanced ultrasound at 12 months. The association between AAA diameter, age, COPD, smoking, anticoagulant therapy, and AAA sac embolization with ELIIp was evaluated using multiple logistic regression. The primary endpoint was the effectiveness of the intra-procedural AAA sac embolization for ELIIp prevention. Secondary endpoints were AAA sac evolution and freedom from ELIIp and embolization related re-interventions at 6-12 months. Seventy patients were analyzed: 26 Group A and 44 Group B; the groups were homogeneous for clinical/morphological characteristics. In Group A the median number of coils positioned in AAA sac was 4.1 (IQR 1). There were no complications related to the embolization procedures. A significantly lower number of ELIIp was detected in Group A than in Group B (8/26 vs. 33/44, respectively, p < .001) at discharge, and this was confirmed at 6-12 months (7/26 vs. 30/44 respectively, p = .001, and 5/25 vs. 32/44, respectively, p < .001). On multivariate analysis, intra-procedural AAA sac embolization was the only factor independently associated with freedom from ELIIp at 6 (OR 0.196, 95% CI 0.06-0.63; p = .007) and 12 months (OR 0.098, 95% CI 0.02-0.35; p < .001). No differences in median AAA sac diameter shrinkage were detected between the two groups at 6-12 months (p = .42 and p = .58, respectively). Freedom from ELIIp related and embolization related re-interventions was 100% in both groups, at 6 and 12 months. Selective intra-procedural AAA sac embolization in patients with p-MRF is safe and could be an effective method to reduce ELIIp. Further studies are mandatory to support these results at long-term follow up. Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Large scale structures in a turbulent boundary layer and their imprint on wall shear stress

NASA Astrophysics Data System (ADS)

Pabon, Rommel; Barnard, Casey; Ukeiley, Lawrence; Sheplak, Mark

2015-11-01

Experiments were performed on a turbulent boundary layer developing on a flat plate model under zero pressure gradient flow. A MEMS differential capacitive shear stress sensor with a 1 mm × 1 mm floating element was used to capture the fluctuating wall shear stress simultaneously with streamwise velocity measurements from a hot-wire anemometer traversed in the wall normal direction. Near the wall, the peak in the cross correlation corresponds to an organized motion inclined 45° from the wall. In the outer region, the peak diminishes in value, but is still significant at a distance greater than half the boundary layer thickness, and corresponds to a structure inclined 14° from the wall. High coherence between the two signals was found for the low-frequency content, reinforcing the belief that large scale structures have a vital impact on wall shear stress. Thus, estimation of the wall shear stress from the low-frequency velocity signal will be performed, and is expected to be statistically significant in the outer boundary layer. Additionally, conditionally averaged mean velocity profiles will be presented to assess the effects of high and low shear stress. This material is based upon work supported by the National Science Foundation Graduate Research Fellowship under Grant No. DGE-1315138.

Elastic-Plastic Thermal Stress Analysis of a High-Pressure Cryogenic Storage Tank

NASA Technical Reports Server (NTRS)

Barker, J. Mark; Field, Robert E. (Technical Monitor)

2003-01-01

The thermal stresses on a cryogenic storage tank contribute strongly to the state of stress of the tank material and its ability to withstand operational stresses. These thermal stresses also affect the growth of any surface damage that might occur in the tank walls. These stresses are particularly of concern during the initial cooldown period for a new tank placed into service, and during any subsequent thermal cycles. A previous preliminary elastic analysis showed that the thermal stress on the inner wall would reach approximately 1,000MPa (145,000 psi). This stress far exceeds the ASTM specified room temperature values for both yield (170MPa) and ultimate (485 MPa) strength for 304L stainless steel. The present analysis determines the thermal stresses using an elastic-plastic model. The commercial software application ANSYS was used to determine the transient spatial temperature profile and the associated spatial thermal stress profiles in a segment of a thick-walled vessel during a typical cooldown process. A strictly elastic analysis using standard material properties for 304L stainless steel showed that the maximum thermal stress on the inner and outer walls was approximately 960 MPa (tensile) and - 270 MPa (compressive) respectively. These values occurred early in the cooldown process, but at different times, An elastic-plastic analysis showed significantly reducing stress, as expected due to the plastic deformation of the material. The maximum stress for the inner wall was approximately 225 MPa (tensile), while the maximum stress for the outer wall was approximately - 130 MPa (compressive).

The Mitochondrial m-AAA Protease Prevents Demyelination and Hair Greying.

PubMed

Wang, Shuaiyu; Jacquemyn, Julie; Murru, Sara; Martinelli, Paola; Barth, Esther; Langer, Thomas; Niessen, Carien M; Rugarli, Elena I

2016-12-01

The m-AAA protease preserves proteostasis of the inner mitochondrial membrane. It ensures a functional respiratory chain, by controlling the turnover of respiratory complex subunits and allowing mitochondrial translation, but other functions in mitochondria are conceivable. Mutations in genes encoding subunits of the m-AAA protease have been linked to various neurodegenerative diseases in humans, such as hereditary spastic paraplegia and spinocerebellar ataxia. While essential functions of the m-AAA protease for neuronal survival have been established, its role in adult glial cells remains enigmatic. Here, we show that deletion of the highly expressed subunit AFG3L2 in mature mouse oligodendrocytes provokes early-on mitochondrial fragmentation and swelling, as previously shown in neurons, but causes only late-onset motor defects and myelin abnormalities. In contrast, total ablation of the m-AAA protease, by deleting both Afg3l2 and its paralogue Afg3l1, triggers progressive motor dysfunction and demyelination, owing to rapid oligodendrocyte cell death. Surprisingly, the mice showed premature hair greying, caused by progressive loss of melanoblasts that share a common developmental origin with Schwann cells and are targeted in our experiments. Thus, while both neurons and glial cells are dependant on the m-AAA protease for survival in vivo, complete ablation of the complex is necessary to trigger death of oligodendrocytes, hinting to cell-autonomous thresholds of vulnerability to m-AAA protease deficiency.

Polymorphisms of the matrix metalloproteinase 9 gene and abdominal aortic aneurysm.

PubMed

Smallwood, L; Allcock, R; van Bockxmeer, F; Warrington, N; Palmer, L J; Iacopetta, B; Golledge, J; Norman, P E

2008-10-01

Increased matrix metalloproteinase (MMP) 9 activity has been implicated in the formation of abdominal aortic aneurysm (AAA). The aim was to explore the association between potentially functional variants of the MMP-9 gene and AAA. The -1562C > T and -1811A > T variants of the MMP-9 gene were genotyped in 678 men with an AAA (at least 30 mm in diameter) and 659 control subjects (aortic diameter 19-22 mm) recruited from a population-based trial of screening for AAA. Levels of MMP-9 were measured in a random subset of 300 cases and 84 controls. The association between genetic variants (including haplotypes) and AAA was assessed by multivariable logistic regression. There was no association between the MMP-9-1562C > T (odds ratio (OR) 0.70 (95 per cent confidence interval (c.i.) 0.27 to 1.82)) or -1811A > T (OR 0.71 (95 per cent c.i. 0.28 to 1.85)) genotypes, or the most common haplotype (OR 0.81 (95 per cent c.i. 0.62 to 1.05)) and AAA. The serum MMP-9 concentration was higher in cases than controls, and in minor allele carriers in cases and controls, although the differences were not statistically significant. In this study, the genetic tendency to higher levels of circulating MMP-9 was not associated with AAA.

Polymorphisms of the MMP-9 gene and abdominal aortic aneurysm

PubMed Central

Smallwood, Linda; Allcock, Richard; van Bockxmeer, Frank; Warrington, Nicole; Palmer, Lyle J; Iacopetta, Barry; Golledge, Jonathan; Norman, Paul E

2008-01-01

Background Increased matrix metalloproteinase-9 (MMP-9) activity has been implicated in the formation of abdominal aortic aneurysms (AAAs). The aim of the present study was to explore the association between potentially functional variants of the MMP-9 gene and AAA. Method The −1562C>T and −1811A>T variants of the MMP-9 gene were genotyped in 678 men with AAAs (>30mm in diameter) and 659 controls (aortic diameter 19−22mm) recruited from a population-based trial of screening for AAAs. The levels of MMP-9 were measured in a random subset of 300 cases and 84 controls. The association between genetic variants (including haplotypes) and AAA was assessed using multivariate logistic regression. Results There was no association between the MMP-9 −1562C>T (OR 0.70 95%CI 0.27, 1.82) or −1811A>T (OR 0.71, 95%CI 0.28, 1.85) genotypes, or the most common haplotype (OR 0.81 95%CI 0.62, 1.05), and AAA. The serum MMP-9 concentration (ng/mL) was higher in cases than controls and in minor allele carriers in cases and controls although the differences were not statistically significant. Conclusion The results suggest that a genetic tendency to have higher levels of circulating MMP-9 is not associated with AAAs. PMID:18763261

Differential proteome analysis during early somatic embryogenesis in Musa spp. AAA cv. Grand Naine.

PubMed

Kumaravel, Marimuthu; Uma, Subbaraya; Backiyarani, Suthanthiram; Saraswathi, Marimuthu Somasundaram; Vaganan, Muthu Mayil; Muthusamy, Muthusamy; Sajith, Kallu Purayil

2017-01-01

Endogenous hormone secretion proteins along with stress and defense proteins play predominant role in banana embryogenesis. This study reveals the underlying molecular mechanism during transition from vegetative to embryogenic state. Banana (Musa spp.) is well known globally as a food fruit crop for millions. The requirement of quality planting material of banana is enormous. Although mass multiplication through tissue culture is in vogue, high-throughput techniques like somatic embryogenesis (SE) as a mass multiplication tool needs to be improved. Apart from clonal propagation, SE has extensive applications in genetic improvement and mutation. SE in banana is completely genome-dependent and most of the commercial cultivars exhibit recalcitrance. Thus, understanding the molecular basis of embryogenesis in Musa will help to develop strategies for mass production of quality planting material. In this study, differentially expressed proteins between embryogenic calli (EC) and non-embryogenic calli (NEC) with respect to the explant, immature male flower buds (IMFB), of cv. Grand Naine (AAA) were determined using two-dimensional gel electrophoresis (2DE). The 2DE results were validated through qRT-PCR. In total, 65 proteins were identified: 42 were highly expressed and 23 were less expressed in EC compared to NEC and IMFB. qRT-PCR analysis of five candidate proteins, upregulated in EC, were well correlated with expression at transcript level. Further analysis of proteins showed that embryogenesis in banana is associated with the control of oxidative stress. The regulation of ROS scavenging system and protection of protein structure occurred in the presence of heat shock proteins. Alongside, high accumulation of stress-related cationic peroxidase and plant growth hormone-related proteins like indole-3-pyruvate monooxygenase and adenylate isopentenyltransferase in EC revealed the association with the induction of SE.

Analysis of a Typical Chinese High School Biology Textbook Using the AAAS Textbook Standards

ERIC Educational Resources Information Center

Liang, Ye; Cobern, William W.

2013-01-01

The purpose of this study was to evaluate a typical Chinese high school biology textbook using the textbook standards of the American Association for the Advancement of Science (AAAS). The data were composed of three chapters selected from the textbook. Each chapter was analyzed and rated using the AAAS textbook standards. Pearson correlations…

40 CFR 78.1 - Purpose and scope.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., subparts AAA through III of part 96 of this chapter or State regulations approved under § 51.124(o)(1) or... HHHH of part 60 of this chapter, subparts AA through II of part 96 of this chapter, subparts AAA... chapter. (8) Under subparts AAA through III of part 96 of this chapter, (i) The decision on the deduction...

40 CFR 280.104 - Local government bond rating test.

Code of Federal Regulations, 2010 CFR

2010-07-01

... million or more, excluding refunded obligations, with a Moody's rating of Aaa, Aa, A, or Baa, or a Standard & Poor's rating of AAA, AA, A, or BBB. Where a local government has multiple outstanding issues... bonds of $1 million or more, excluding refunded issues and by also having a Moody's rating of Aaa, A, A...

External validation of Vascular Study Group of New England risk predictive model of mortality after elective abdominal aorta aneurysm repair in the Vascular Quality Initiative and comparison against established models.

PubMed

Eslami, Mohammad H; Rybin, Denis V; Doros, Gheorghe; Siracuse, Jeffrey J; Farber, Alik

2018-01-01

The purpose of this study is to externally validate a recently reported Vascular Study Group of New England (VSGNE) risk predictive model of postoperative mortality after elective abdominal aortic aneurysm (AAA) repair and to compare its predictive ability across different patients' risk categories and against the established risk predictive models using the Vascular Quality Initiative (VQI) AAA sample. The VQI AAA database (2010-2015) was queried for patients who underwent elective AAA repair. The VSGNE cases were excluded from the VQI sample. The external validation of a recently published VSGNE AAA risk predictive model, which includes only preoperative variables (age, gender, history of coronary artery disease, chronic obstructive pulmonary disease, cerebrovascular disease, creatinine levels, and aneurysm size) and planned type of repair, was performed using the VQI elective AAA repair sample. The predictive value of the model was assessed via the C-statistic. Hosmer-Lemeshow method was used to assess calibration and goodness of fit. This model was then compared with the Medicare, Vascular Governance Northwest model, and Glasgow Aneurysm Score for predicting mortality in VQI sample. The Vuong test was performed to compare the model fit between the models. Model discrimination was assessed in different risk group VQI quintiles. Data from 4431 cases from the VSGNE sample with the overall mortality rate of 1.4% was used to develop the model. The internally validated VSGNE model showed a very high discriminating ability in predicting mortality (C = 0.822) and good model fit (Hosmer-Lemeshow P = .309) among the VSGNE elective AAA repair sample. External validation on 16,989 VQI cases with an overall 0.9% mortality rate showed very robust predictive ability of mortality (C = 0.802). Vuong tests yielded a significant fit difference favoring the VSGNE over then Medicare model (C = 0.780), Vascular Governance Northwest (0.774), and Glasgow Aneurysm Score (0.639). Across the 5 risk quintiles, the VSGNE model predicted observed mortality significantly with great accuracy. This simple VSGNE AAA risk predictive model showed very high discriminative ability in predicting mortality after elective AAA repair among a large external independent sample of AAA cases performed by a diverse array of physicians nationwide. The risk score based on this simple VSGNE model can reliably stratify patients according to their risk of mortality after elective AAA repair better than other established models. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Does continuous trusted adult support in childhood impart life-course resilience against adverse childhood experiences - a retrospective study on adult health-harming behaviours and mental well-being.

PubMed

Bellis, Mark A; Hardcastle, Katie; Ford, Kat; Hughes, Karen; Ashton, Kathryn; Quigg, Zara; Butler, Nadia

2017-03-23

Adverse childhood experiences (ACEs) including child abuse and household problems (e.g. domestic violence) increase risks of poor health and mental well-being in adulthood. Factors such as having access to a trusted adult as a child may impart resilience against developing such negative outcomes. How much childhood adversity is mitigated by such resilience is poorly quantified. Here we test if access to a trusted adult in childhood is associated with reduced impacts of ACEs on adoption of health-harming behaviours and lower mental well-being in adults. Cross-sectional, face-to-face household surveys (aged 18-69 years, February-September 2015) examining ACEs suffered, always available adult (AAA) support from someone you trust in childhood and current diet, smoking, alcohol consumption and mental well-being were undertaken in four UK regions. Sampling used stratified random probability methods (n = 7,047). Analyses used chi squared, binary and multinomial logistic regression. Adult prevalence of poor diet, daily smoking and heavier alcohol consumption increased with ACE count and decreased with AAA support in childhood. Prevalence of having any two such behaviours increased from 1.8% (0 ACEs, AAA support, most affluent quintile of residence) to 21.5% (≥4 ACEs, lacking AAA support, most deprived quintile). However, the increase was reduced to 7.1% with AAA support (≥4 ACEs, most deprived quintile). Lower mental well-being was 3.27 (95% CIs, 2.16-4.96) times more likely with ≥4 ACEs and AAA support from someone you trust in childhood (vs. 0 ACE, with AAA support) increasing to 8.32 (95% CIs, 6.53-10.61) times more likely with ≥4 ACEs but without AAA support in childhood. Multiple health-harming behaviours combined with lower mental well-being rose dramatically with ACE count and lack of AAA support in childhood (adjusted odds ratio 32.01, 95% CIs 18.31-55.98, ≥4 ACEs, without AAA support vs. 0 ACEs, with AAA support). Adverse childhood experiences negatively impact mental and physical health across the life-course. Such impacts may be substantively mitigated by always having support from an adult you trust in childhood. Developing resilience in children as well as reducing childhood adversity are critical if low mental well-being, health-harming behaviours and their combined contribution to non-communicable disease are to be reduced.

Time-varying wall stress: an index of ventricular vascular coupling.

PubMed

Dell'Italia, L J; Blackwell, G G; Thorn, B T; Pearce, D J; Bishop, S P; Pohost, G M

1992-08-01

Previous work in the isolated heart and intact circulation has suggested that the relationship between wall stress and time during left ventricular (LV) ejection is linear and that the slope, which will be referred to as time-varying wall stress, increases in response to augmentation in afterload. However, the etiology of the increase in slope has not been determined in an intact animal. Magnetic resonance imaging coupled with high-fidelity LV pressure measurement using a nonferrous catheter-tip manometer generates a detailed assessment of wall stress in an animal model where the thorax and pericardium have never been disturbed. Accordingly, six anesthetized dogs were studied during autonomic blockade with atropine and propranolol during angiotensin infusion, producing three widely disparate left ventricular systolic pressures (87 +/- 7 vs. 124 +/- 13 vs. 152 +/- 10 mmHg, P less than 0.001). Time-varying wall stress did not change from low to medium load (-42.4 +/- 9.5 to -27.3 +/- 22.3 g.cm-2.ms-1) but increased significantly at high load (-21.7 +/- 14.9 g.cm-2.ms-1, P less than 0.05). Analysis of the relative contribution of pressure, chamber radius, wall thickness, and long-axis dimension to the changes in time-varying wall stress demonstrated only the pressure component to change its relative contribution at medium (P less than 0.001) and high load (P less than 0.001). Therefore, we conclude that the increase in time-varying wall stress results from augmentation of pressure in the latter one-half of systole that is incompletely offset by shortening and wall thickening.(ABSTRACT TRUNCATED AT 250 WORDS)

Cost-effectiveness of intensive smoking cessation therapy among patients with small abdominal aortic aneurysms.

PubMed

Mani, Kevin; Wanhainen, Anders; Lundkvist, Jonas; Lindström, David

2011-09-01

Smoking cessation is one of the few available strategies to decrease the risk for expansion and rupture of small abdominal aortic aneurysms (AAAs). The cost-effectiveness of an intensive smoking cessation therapy in patients with small AAAs identified at screening was evaluated. A Markov cohort simulation model was used to compare an 8-week smoking cessation intervention with adjuvant pharmacotherapy and annual revisits vs nonintervention among 65-year-old male smokers with a small AAA identified at screening. The smoking cessation rate was tested in one-way sensitivity analyses in the intervention group (range, 22%-57%) and in the nonintervention group (range, 3%-30%). Literature data on the effect of smoking on AAA expansion and rupture was factored into the model. The intervention was cost-effective in all tested scenarios and sensitivity analyses. The smoking cessation intervention was cost-effective due to a decreased need for AAA repair and decreased rupture rate even when disregarding the positive effects of smoking cessation on long-term survival. The incremental cost/effectiveness ratio reached the willingness-to-pay threshold value of €25,000 per life-year gained when assuming an intervention cost of > €3250 or an effect of ≤ 1% difference in long-term smoking cessation between the intervention and nonintervention groups. Smoking cessation resulted in a relative risk reduction for elective AAA repair by 9% and for rupture by 38% over 10 years of follow-up. An adequate smoking cessation intervention in patients with small AAAs identified at screening can cost-effectively increase long-term survival and decrease the need for AAA repair. Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Editor's Choice - Inequalities in Abdominal Aortic Aneurysm Screening in England: Effects of Social Deprivation and Ethnicity.

PubMed

Jacomelli, J; Summers, L; Stevenson, A; Lees, T; Earnshaw, J J

2017-06-01

Population screening for abdominal aortic aneurysm (AAA) in men is currently ongoing in several countries. The aim was to examine the effects of deprivation and ethnicity on uptake of screening for abdominal aortic aneurysm (AAA) and prevalence of AAA. This was a review of outcomes from a population screening programme using data collected contemporaneously on a bespoke national database. Men aged 65 in two annual cohorts (2013/14 and 2014/15) were invited for AAA screening. Attendance and prevalence of AAA (aortic diameter >2.9 cm) were recorded. Results were compared according to measures of social deprivation and recorded ethnicity. Some 593,032 men were invited and 461,898 attended for ultrasound screening; uptake 77.9%. Uptake was related to social deprivation: 65.1% in the most deprived decile, 84.1% in the least deprived: OR for least deprived 2.84, 95% CI 2.76-2.92, p<.0001. Men in deprived areas were more likely to actively decline screening: 6% versus 3.8% in the least deprived decile. AAA were twice as common in the most deprived compared with the least deprived decile: OR 2.1, 95% CI 1.77-2.27, p<.0001. AAA were more common in white British men than in black (OR 0.46, 95% CI 0.31-0.71) or Asian (OR 0.18, 95% CI 0.13-0.26) men. There was considerable local variation in all findings. Social deprivation affects uptake of AAA screening in 65 year old men. Local factors are the most important determinants of uptake, so solutions to improve uptake must be designed at local, not national level. Copyright © 2017 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Somatic HLA Mutations Expose the Role of Class I-Mediated Autoimmunity in Aplastic Anemia and its Clonal Complications.

PubMed

Babushok, Daria V; Duke, Jamie L; Xie, Hongbo M; Stanley, Natasha; Atienza, Jamie; Perdigones, Nieves; Nicholas, Peter; Ferriola, Deborah; Li, Yimei; Huang, Hugh; Ye, Wenda; Morrissette, Jennifer J D; Kearns, Jane; Porter, David L; Podsakoff, Gregory M; Eisenlohr, Laurence C; Biegel, Jaclyn A; Chou, Stella T; Monos, Dimitrios S; Bessler, Monica; Olson, Timothy S

2017-10-10

Acquired aplastic anemia (aAA) is an acquired deficiency of early hematopoietic cells, characterized by inadequate blood production, and a predisposition to myelodysplastic syndrome (MDS) and leukemia. Although its exact pathogenesis is unknown, aAA is thought to be driven by Human Leukocyte Antigen (HLA)-restricted T cell immunity, with earlier studies favoring HLA class II-mediated pathways. Using whole exome sequencing (WES), we recently identified two aAA patients with somatic mutations in HLA class I genes. We hypothesized that HLA class I mutations are pathognomonic for autoimmunity in aAA, but were previously underappreciated because the Major Histocompatibility Complex (MHC) region is notoriously difficult to analyze by WES. Using a combination of targeted deep sequencing of HLA class I genes and single nucleotide polymorphism array (SNP-A) genotyping we screened 66 aAA patients for somatic HLA class I loss. We found somatic HLA loss in eleven patients (17%), with thirteen loss-of-function mutations in HLA-A *33:03, HLA-A *68:01, HLA-B *14:02 and HLA-B *40:02 alleles. Three patients had more than one mutation targeting the same HLA allele. Interestingly, HLA-B *14:02 and HLA-B *40:02 were significantly overrepresented in aAA patients, compared to ethnicity-matched controls. Patients who inherited the targeted HLA alleles, regardless of HLA mutation status, had a more severe disease course with more frequent clonal complications as assessed by WES, SNP-A, and metaphase cytogenetics, and more frequent secondary MDS. The finding of recurrent HLA class I mutations provides compelling evidence for a predominant HLA class I-driven autoimmunity in aAA, and establishes a novel link between aAA patients' immunogenetics and clonal evolution.

Somatic HLA mutations expose the role of class I–mediated autoimmunity in aplastic anemia and its clonal complications

PubMed Central

Duke, Jamie L.; Xie, Hongbo M.; Stanley, Natasha; Atienza, Jamie; Perdigones, Nieves; Nicholas, Peter; Ferriola, Deborah; Li, Yimei; Huang, Hugh; Ye, Wenda; Morrissette, Jennifer J. D.; Kearns, Jane; Porter, David L.; Podsakoff, Gregory M.; Eisenlohr, Laurence C.; Biegel, Jaclyn A.; Chou, Stella T.; Monos, Dimitrios S.; Bessler, Monica; Olson, Timothy S.

2017-01-01

Acquired aplastic anemia (aAA) is an acquired deficiency of early hematopoietic cells, characterized by inadequate blood production, and a predisposition to myelodysplastic syndrome (MDS) and leukemia. Although its exact pathogenesis is unknown, aAA is thought to be driven by human leukocyte antigen (HLA)–restricted T cell immunity, with earlier studies favoring HLA class II-mediated pathways. Using whole-exome sequencing (WES), we recently identified 2 patients with aAA with somatic mutations in HLA class I genes. We hypothesized that HLA class I mutations are pathognomonic for autoimmunity in aAA, but were previously underappreciated because the major histocompatibility complex (MHC) region is notoriously difficult to analyze by WES. Using a combination of targeted deep sequencing of HLA class I genes and single nucleotide polymorphism array (SNP-A) genotyping, we screened 66 patients with aAA for somatic HLA class I loss. We found somatic HLA loss in 11 patients (17%), with 13 loss-of-function mutations in HLA-A*33:03, HLA-A*68:01, HLA-B*14:02, and HLA-B*40:02 alleles. Three patients had more than 1 mutation targeting the same HLA allele. Interestingly, HLA-B*14:02 and HLA-B*40:02 were significantly overrepresented in patients with aAA compared with ethnicity-matched controls. Patients who inherited the targeted HLA alleles, regardless of HLA mutation status, had a more severe disease course with more frequent clonal complications as assessed by WES, SNP-A, and metaphase cytogenetics, and more frequent secondary MDS. The finding of recurrent HLA class I mutations provides compelling evidence for a predominant HLA class I-driven autoimmunity in aAA and establishes a novel link between immunogenetics and clonal evolution of patients with aAA. PMID:28971166

Markers of vitamin D metabolism and incidence of clinically diagnosed abdominal aortic aneurysm: The Atherosclerosis Risk in Communities Study.

PubMed

Lutsey, Pamela L; Rooney, Mary R; Folsom, Aaron R; Michos, Erin D; Alonso, Alvaro; Tang, Weihong

2018-06-01

Little is known about whether markers of vitamin D metabolism are associated with the development of abdominal aortic aneurysm (AAA), though these markers have been linked to other cardiovascular diseases. We tested the hypotheses that risk of AAA is higher among individuals with low serum concentrations of 25-hydroxy vitamin D [25(OH)D], and among those with elevated concentrations of calcium, fibroblast growth factor 23 (FGF23), phosphorus, and parathyroid hormone (PTH) using data from a cohort of black and white individuals with long-term follow-up. Markers of vitamin D metabolism were measured using serum collected in 1990-1992 from ARIC study participants (mean ± SD age 56.9 ± 5.7 years, 43.2% male, 23.9% black). A total of 12,770 participants were followed until 2011 for incident AAA. Multivariable-adjusted Cox regression models were used. A total of 449 incident AAA events occurred over a median follow-up of 19.7 years. For the association between serum calcium and risk of incident AAA there was evidence of interaction by sex ( p-interaction 0.02). Among women, in the fully adjusted model, the hazard ratio (95% confidence interval) comparing the highest to lowest quartile was 2.43 (1.25-4.73), whereas in men it was 1.01 (0.72-1.43). Not associated with risk of incident AAA were 25(OH)D, FGF23, phosphorus, and PTH. In this large prospective cohort, there was little evidence that markers of vitamin D metabolism are associated with risk of incident AAA. The positive association of calcium with AAA among women may warrant further investigation and replication in other populations.

Regionalization of Emergent Vascular Surgery for Patients With Ruptured AAA Improves Outcomes.

PubMed

Warner, Courtney J; Roddy, Sean P; Chang, Benjamin B; Kreienberg, Paul B; Sternbach, Yaron; Taggert, John B; Ozsvath, Kathleen J; Stain, Steven C; Darling, R Clement

2016-09-01

Safe and efficient endovascular aneurysm repair (EVAR) for ruptured abdominal aortic aneurysm (r-AAA) requires advanced infrastructure and surgical expertise not available at all US hospitals. The objective was to assess the impact of regionalizing r-AAA care to centers equipped for both open surgical repair (r-OSR) and EVAR (r-EVAR) by vascular surgeons. A retrospective review of all patients with r-AAA undergoing open or endovascular repair in a 12-hospital region. Patient demographics, transfer status, type of repair, and intraoperative variables were recorded. Outcomes included perioperative morbidity and mortality. Four hundred fifty-one patients with r-AAA were treated from 2002 to 2015. Three hundred twenty-one patients (71%) presented initially to community hospitals (CHs) and 130 (29%) presented to the tertiary medical center (MC). Of the 321 patients presenting to CH, 133 (41%) were treated locally (131 OSR; 2 EVAR) and 188 (59%) were transferred to the MC. In total, 318 patients were treated at the MC (122 OSR; 196 EVAR). At the MC, r-EVAR was associated with a lower mortality rate than r-OSR (20% vs 37%, P = 0.001). Transfer did not influence r-EVAR mortality (20% in r-EVAR presenting to MC vs 20% in r-EVAR transferred, P > 0.2). Overall, r-AAA mortality at the MC was 20% lower than CH (27% vs 46%, P < 0.001). Regionalization of r-AAA repair to centers equipped for both r-EVAR and r-OSR decreased mortality by approximately 20%. Transfer did not impact the mortality of r-EVAR at the tertiary center. Care of r-AAA in the US should be centralized to centers equipped with available technology and vascular surgeons.

The impact of endovascular aneurysm repair on mortality for elective abdominal aortic aneurysm repair in England and the United States.

PubMed

Karthikesalingam, Alan; Holt, Peter J; Vidal-Diez, Alberto; Bahia, Sandeep S; Patterson, Benjamin O; Hinchliffe, Robert J; Thompson, Matthew M

2016-08-01

Procedural mortality is of paramount importance for patients undergoing elective abdominal aortic aneurysm (AAA) repair. Previous comparative studies have demonstrated international differences in the care of ruptured AAA. This study compared the use of endovascular aneurysm repair (EVAR) and in-hospital mortality for elective AAA repair in England and the United States. The English Hospital Episode Statistics and the U.S. Nationwide Inpatient Sample (NIS) were interrogated for elective AAA repair from 2005 to 2010. In-hospital mortality and the use of EVAR were analyzed separately for each health care system, after within-country risk adjustment for age, gender, year, and an accepted national comorbidity index. The study included 21,272 patients with AAA in England, of whom 86.61% were male, with median (interquartile range) age of 74 (69-79) years. There were 196,113 AAA patients in the United States, of whom 76.14% were male, with median (interquartile range) age of 73 (67-78) years. In-hospital mortality was greater in England (4.09% vs 1.96 %; P < .01) and EVAR less common (37.33% vs 64.36%; P < .01). These observations persisted in age- and gender-matched comparison. In both countries, lower mortality and greater use of EVAR were seen in centers performing greater numbers of AAA repairs per annum. In England, lower mortality and greater use of EVAR were seen in teaching hospitals with larger bed capacity. In-hospital survival and the uptake of EVAR are lower in England than in the United States. In both countries, mortality was lowest in high-caseload centers performing a greater proportion of cases with endovascular repair. These common factors suggest strategies for improving outcomes for patients requiring elective AAA repair. Copyright © 2016. Published by Elsevier Inc.

On the optimization of low-cost FDM 3D printers for accurate replication of patient-specific abdominal aortic aneurysm geometry.

PubMed

Chung, Michael; Radacsi, Norbert; Robert, Colin; McCarthy, Edward D; Callanan, Anthony; Conlisk, Noel; Hoskins, Peter R; Koutsos, Vasileios

2018-01-01

There is a potential for direct model manufacturing of abdominal aortic aneurysm (AAA) using 3D printing technique for generating flexible semi-transparent prototypes. A patient-specific AAA model was manufactured using fused deposition modelling (FDM) 3D printing technology. A flexible, semi-transparent thermoplastic polyurethane (TPU), called Cheetah Water (produced by Ninjatek, USA), was used as the flexible, transparent material for model manufacture with a hydrophilic support structure 3D printed with polyvinyl alcohol (PVA). Printing parameters were investigated to evaluate their effect on 3D-printing precision and transparency of the final model. ISO standard tear resistance tests were carried out on Ninjatek Cheetah specimens for a comparison of tear strength with silicone rubbers. It was found that an increase in printing speed decreased printing accuracy, whilst using an infill percentage of 100% and printing nozzle temperature of 255 °C produced the most transparent results. The model had fair transparency, allowing external inspection of model inserts such as stent grafts, and good flexibility with an overall discrepancy between CAD and physical model average wall thicknesses of 0.05 mm (2.5% thicker than the CAD model). The tear resistance test found Ninjatek Cheetah TPU to have an average tear resistance of 83 kN/m, higher than any of the silicone rubbers used in previous AAA model manufacture. The model had lower cost (4.50 GBP per model), shorter manufacturing time (25 h 3 min) and an acceptable level of accuracy (2.61% error) compared to other methods. It was concluded that the model would be of use in endovascular aneurysm repair planning and education, particularly for practicing placement of hooked or barbed stents, due to the model's balance of flexibility, transparency, robustness and cost-effectiveness.

The pupylation machinery is involved in iron homeostasis by targeting the iron storage protein ferritin.

PubMed

Küberl, Andreas; Polen, Tino; Bott, Michael

2016-04-26

The balance of sufficient iron supply and avoidance of iron toxicity by iron homeostasis is a prerequisite for cellular metabolism and growth. Here we provide evidence that, in Actinobacteria, pupylation plays a crucial role in this process. Pupylation is a posttranslational modification in which the prokaryotic ubiquitin-like protein Pup is covalently attached to a lysine residue in target proteins, thus resembling ubiquitination in eukaryotes. Pupylated proteins are recognized and unfolded by a dedicated AAA+ ATPase (Mycobacterium proteasomal AAA+ ATPase; ATPase forming ring-shaped complexes). In Mycobacteria, degradation of pupylated proteins by the proteasome serves as a protection mechanism against several stress conditions. Other bacterial genera capable of pupylation such as Corynebacterium lack a proteasome, and the fate of pupylated proteins is unknown. We discovered that Corynebacterium glutamicum mutants lacking components of the pupylation machinery show a strong growth defect under iron limitation, which was caused by the absence of pupylation and unfolding of the iron storage protein ferritin. Genetic and biochemical data support a model in which the pupylation machinery is responsible for iron release from ferritin independent of degradation.

The pupylation machinery is involved in iron homeostasis by targeting the iron storage protein ferritin

PubMed Central

Küberl, Andreas; Polen, Tino; Bott, Michael

2016-01-01

The balance of sufficient iron supply and avoidance of iron toxicity by iron homeostasis is a prerequisite for cellular metabolism and growth. Here we provide evidence that, in Actinobacteria, pupylation plays a crucial role in this process. Pupylation is a posttranslational modification in which the prokaryotic ubiquitin-like protein Pup is covalently attached to a lysine residue in target proteins, thus resembling ubiquitination in eukaryotes. Pupylated proteins are recognized and unfolded by a dedicated AAA+ ATPase (Mycobacterium proteasomal AAA+ ATPase; ATPase forming ring-shaped complexes). In Mycobacteria, degradation of pupylated proteins by the proteasome serves as a protection mechanism against several stress conditions. Other bacterial genera capable of pupylation such as Corynebacterium lack a proteasome, and the fate of pupylated proteins is unknown. We discovered that Corynebacterium glutamicum mutants lacking components of the pupylation machinery show a strong growth defect under iron limitation, which was caused by the absence of pupylation and unfolding of the iron storage protein ferritin. Genetic and biochemical data support a model in which the pupylation machinery is responsible for iron release from ferritin independent of degradation. PMID:27078093

Aortic stent grafting: a new approach to a deadly diagnosis: one hospital's findings in defining new care processes.

PubMed

Kalinowski, H

2001-01-01

Ruptured abdominal aortic aneurysm (AAA) is the 13th leading cause of death in the United States. Diagnosis is the key to prevention of death from AAA. Millions of Americans harbor this silent, potentially lethal aneurysm. For over 50 years, conventional open surgical repair has been performed for ruptured aortic abdominal aneurysm. It is a major operation with an extended hospital stay and recovery period. An alternative approach to AAA repair has evolved over the past 10 years that combines advances in catheter and stent technologies. With the AAA aortic stent graft, patients usually do not require intensive care and are discharged home within 48 hours of the procedure. This article describes the AAA aortic stent graft procedure, in the formation of a case management team to develop a clinical pathway and standing orders for these patients and defines the outcomes of care.

Advanced, Analytic, Automated (AAA) Measurement of Engagement During Learning

PubMed Central

D’Mello, Sidney; Dieterle, Ed; Duckworth, Angela

2017-01-01

It is generally acknowledged that engagement plays a critical role in learning. Unfortunately, the study of engagement has been stymied by a lack of valid and efficient measures. We introduce the advanced, analytic, and automated (AAA) approach to measure engagement at fine-grained temporal resolutions. The AAA measurement approach is grounded in embodied theories of cognition and affect, which advocate a close coupling between thought and action. It uses machine-learned computational models to automatically infer mental states associated with engagement (e.g., interest, flow) from machine-readable behavioral and physiological signals (e.g., facial expressions, eye tracking, click-stream data) and from aspects of the environmental context. We present15 case studies that illustrate the potential of the AAA approach for measuring engagement in digital learning environments. We discuss strengths and weaknesses of the AAA approach, concluding that it has significant promise to catalyze engagement research. PMID:29038607

Canine Outreach Promoting Engagement: The Effect of Meaningful Activities on Students' Attitudes Toward Cognitively Impaired Older Adults.

PubMed

Yordy, B Morgan; Pope, W Stuart; Wang, Chih-Hsuan

2018-06-14

Animal-assisted activities (AAAs) show promise in providing emotional and social benefits to older adults and may be used as a tool to promote therapeutic communication between students and cognitively impaired older adults. The purpose was to develop a program incorporating AAAs to enhance social engagement of cognitively impaired older adults in a community respite program and in turn enhance student comfort when caring for this vulnerable population. The Dementia Attitudes Scale, a validated tool, was used to measure students' attitudes before and after AAA intervention. Data were analyzed using repeated-measures analysis of variance. Students were significantly more comfortable and demonstrated a gain in knowledge after AAAs were included in the community clinical experience. Incorporating AAAs into student community/service-learning clinical experience improved communication between students and cognitively impaired older adults, improving students' attitudes when caring for this population.

Advanced, Analytic, Automated (AAA) Measurement of Engagement During Learning.

PubMed

D'Mello, Sidney; Dieterle, Ed; Duckworth, Angela

2017-01-01

It is generally acknowledged that engagement plays a critical role in learning. Unfortunately, the study of engagement has been stymied by a lack of valid and efficient measures. We introduce the advanced, analytic, and automated (AAA) approach to measure engagement at fine-grained temporal resolutions. The AAA measurement approach is grounded in embodied theories of cognition and affect, which advocate a close coupling between thought and action. It uses machine-learned computational models to automatically infer mental states associated with engagement (e.g., interest, flow) from machine-readable behavioral and physiological signals (e.g., facial expressions, eye tracking, click-stream data) and from aspects of the environmental context. We present15 case studies that illustrate the potential of the AAA approach for measuring engagement in digital learning environments. We discuss strengths and weaknesses of the AAA approach, concluding that it has significant promise to catalyze engagement research.

Animal-assisted interventions in internal and rehabilitation medicine: a review of the recent literature.

PubMed

Muñoz Lasa, S; Ferriero, G; Brigatti, E; Valero, R; Franchignoni, F

2011-06-01

While conventional wisdom has always affirmed the value of animals in promoting human well-being, only recently has their therapeutic role in medicine become the focus of dedicated research. Therapeutic modalities that use animals as a tool for improving the physical, emotional, cognitive and/or social functioning of humans are called animal-assisted interventions (AAI), and are classified into: animal-assisted activities (AAA); animal-assisted therapy (AAT); and service animal programs (SAP). The aim of this review is to analyze the papers published between 2001 and 2010 in the most influential medical journals dealing with AAI, and discuss their findings in the light of what may be of interest for internal medicine and rehabilitation. A total of 35 articles met the strict inclusion criteria for this review: 18 papers dealing with AAA, 8 with AAT, and 9 with SAP. The therapeutic outcomes associated with AAA are: enhancement of socialization; reduction of stress, anxiety and loneliness; improvement in mood and general well-being; and development of leisure/recreation skills. Regarding AAT, horses are often used as a complementary strategy to facilitate the normalization of muscle tone and improve motor skills in children with cerebral palsy and persons with lower limb spasticity. Finally, most SAP utilize dogs, that assist people with various disabilities in performing everyday activities, thus reducing their dependence on other persons. Further studies are needed to better define the fields and programs for the therapeutic use of animals and to increase their utilization in medicine, as a promising, complementary and natural means to improve both functional autonomy and quality of life.

Mechanical analysis of the strains generated by water tension in plant stems. Part I: stress transmission from the water to the cell walls.

PubMed

Alméras, Tancrède; Gril, Joseph

2007-11-01

Plant tissues shrink and swell in response to changes in water pressure. These strains can be easily measured, e.g., at the surface of tree stems, to obtain indirect information about plant water status and other physiological parameters. We developed a mechanical model to clarify how water pressure is transmitted to cell walls and causes shrinkage of plant tissues, particularly in the case of thick-walled cells such as wood fibers. Our analysis shows that the stress inside the fiber cell walls is lower than the water tension. The difference is accounted for by a stress transmission factor that depends on two main effects. The first effect is the dilution of the stress through the cell wall, because water acts at the lumen border and is transmitted to the outer border of the cell, which has a larger circumference. The second effect is the partial conversion of radial stress into tangential stress. Both effects are quantified as functions of parameters of the cell wall structure and its mechanical properties.

Diagnostic Techniques to Elucidate the Aerodynamic Performance of Acoustic Liners

NASA Technical Reports Server (NTRS)

June, Jason; Bertolucci, Brandon; Ukeiley, Lawrence; Cattafesta, Louis N., III; Sheplak, Mark

2017-01-01

In support of Topic A.2.8 of NASA NRA NNH10ZEA001N, the University of Florida (UF) has investigated the use of flow field optical diagnostic and micromachined sensor-based techniques for assessing the wall shear stress on an acoustic liner. Stereoscopic particle image velocimetry (sPIV) was used to study the velocity field over a liner in the Grazing Flow Impedance Duct (GFID). The results indicate that the use of a control volume based method to determine the wall shear stress is prone to significant error. The skin friction over the liner as measured using velocity curve fitting techniques was shown to be locally reduced behind an orifice, relative to the hard wall case in a streamwise plane centered on the orifice. The capacitive wall shear stress sensor exhibited a linear response for a range of shear stresses over a hard wall. PIV over the liner is consistent with lifting of the near wall turbulent structure as it passes over an orifice, followed by a region of low wall shear stress.

Triglyceride glucose index and common carotid wall shear stress.

PubMed

Tripolino, Cesare; Irace, Concetta; Scavelli, Faustina B; de Franceschi, Maria S; Esposito, Teresa; Carallo, Claudio; Gnasso, Agostino

2014-02-01

Alterations in wall shear stress contribute to both clinical and subclinical atherosclerosis. Several conditions such as hypertension, diabetes, and obesity can impair shear stress, but the role of insulin resistance has never been investigated. The present study was designed to investigate whether insulin resistance assessed by TyG Index associates with wall shear stress in the common carotid artery. One hundred six individuals were enrolled. Blood pressure, lipids, glucose, and cigarette smoking were evaluated. TyG Index was calculated as log[fasting triglycerides × fasting glucose / 2]. Subjects underwent blood viscosity measurement and echo-Doppler evaluation of carotid arteries to calculate wall shear stress. The association between TyG Index and carotid wall shear stress was assessed by simple and multiple regression analyses. TyG Index was significantly and inversely associated with carotid wall shear stress both in simple (r = -0.44, P < 0.001) and multiple regression analyses accounting for age, sex, and major cardiovascular risk factors. The association was further confirmed after exclusion of subjects with diabetes, dyslipidemia, fasting blood glucose greater than 100 mg/dL, and triglycerides greater than 150 mg/dL. The present findings suggest that increasing insulin resistance, as assessed by TyG Index, associates with atherosclerosis-prone shear stress reduction in the common carotid artery.

78 FR 39973 - Application of Section 108(i) to Partnerships and S Corporations

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-03

... (AAA), as defined in section 1368(e)(1), of an S corporation partner that has a deferred amount with... amount in the taxable year of the reacquisition. The AAA of an S corporation partner is not decreased by its share of any deferred OID deduction in the taxable year in which the deferred OID accrues. The AAA...

US Army And The Emergence Of Unmanned Threats

DTIC Science & Technology

2016-05-26

43 iv Acronyms A2/AD Anti-Access/Area Denial AAA Anti-aircraft Artillery ADP Army...possessed sufficient resources and motivation to challenge local air superiority at the bridgehead. 66 Allied anti-aircraft artillery ( AAA ) raced to...Remagen. 482nd AAA , organic to Ninth Armored Division advanced through the division column to emplace at the bridge. With the vulnerability of the

A Quantitative Methodology for Determining the Critical Benchmarks for Project 2061 Strand Maps

ERIC Educational Resources Information Center

Kuhn, G.

2008-01-01

The American Association for the Advancement of Science (AAAS) was tasked with identifying the key science concepts for science literacy in K-12 students in America (AAAS, 1990, 1993). The AAAS Atlas of Science Literacy (2001) has organized roughly half of these science concepts or benchmarks into fifty flow charts. Each flow chart or strand map…

40 CFR 78.3 - Petition for administrative review and request for evidentiary hearing.

Code of Federal Regulations, 2010 CFR

2010-07-01

... for administrative review of a decision of the Administrator that is made under subparts AAA through... Administrator that is made under subparts AAA through III of part 97 and that is appealable under § 78.1(a): (i... of this chapter, subparts AAA through III of part 96 of this chapter, subparts AAAA through IIII of...

--No Title--

Science.gov Websites

;background-color:#ddd;border-bottom:3px solid #aaa;padding:8px;margin-top:12px;height:auto;overflow:hidden }#how_use_car{clear:both;background-color:#ddd;border-bottom:3px solid #aaa;padding:8px;margin-top:20px ;height:auto;overflow:hidden}#results{clear:both;background-color:#ddd;border-bottom:3px solid #aaa;padding:8px

Jaundice as a Rare Indication for Aortic Aneurysm Repair.

PubMed

Rieß, Henrik C; Tsilimparis, Nikolaos; Behrendt, Christian A; Wipper, Sabine; Debus, Eike S; Larena-Avellaneda, Axel

2015-10-01

Compression of adjacent anatomic structures by an abdominal aortic aneurysm (AAA) can result in a variety of symptoms. We describe the case of an 88-year-old Caucasian woman with jaundice, elevated laboratory parameters for extrahepatic and intrahepatic cholestasis, and concomitant juxtarenal AAA compressing the liver hilum. Following exclusion of other common causes for cholestasis, the patient was considered to have a symptomatic AAA. Open abdominal aortic surgery revealed a contained rupture and was repaired. Obstructive jaundice secondary to a compromising AAA is a rare condition and to the best of our knowledge has not been reported to date. Copyright © 2015 Elsevier Inc. All rights reserved.

Development and Characterization of Novel Bioluminecent Systems

DTIC Science & Technology

2013-07-01

Ppy I108R. The following primers and their respective reverse compliments were used: Y447E, 5´- CT TTA ATT AAA TAC AAA GGA GAG CAG GTG GCC CCC GCT G...3´ [EcoRV] and I108R, 5´- GGA GTT GCA GTG GCG CCC GCG AAC GAC CGT TAT AAT GAA CGT-3´ [KasI] (bold represents the mutated codons, underlined...primers and their respective reverse compliments: Y447C, 5´- G AAG TCT TTA ATA AAA TAC AAA GGA TGT CAG GTG GCC CCC GCT G -3´ [PacI] and I108C, 5´- GGA

Deletion of BMAL1 in Smooth Muscle Cells Protects Mice From Abdominal Aortic Aneurysms.

PubMed

Lutshumba, Jenny; Liu, Shu; Zhong, Yu; Hou, Tianfei; Daugherty, Alan; Lu, Hong; Guo, Zhenheng; Gong, Ming C

2018-05-01

Abdominal aortic aneurysm (AAA) has high mortality rate when ruptured, but currently, there is no proven pharmacological therapy for AAA because of our poor understanding of its pathogenesis. The current study explored a novel role of smooth muscle cell (SMC) BMAL1 (brain and muscle Arnt-like protein-1)-a transcription factor known to regulate circadian rhythm-in AAA development. SMC-selective deletion of BMAL1 potently protected mice from AAA induced by (1) MR (mineralocorticoid receptor) agonist deoxycorticosterone acetate or aldosterone plus high salt intake and (2) angiotensin II infusion in hypercholesterolemia mice. Aortic BMAL1 was upregulated by deoxycorticosterone acetate-salt, and deletion of BMAL1 in SMCs selectively upregulated TIMP4 (tissue inhibitor of metalloproteinase 4) and suppressed deoxycorticosterone acetate-salt-induced MMP (matrix metalloproteinase) activation and elastin breakages. Moreover, BMAL1 bound to the Timp4 promoter and suppressed Timp4 transcription. These results reveal an important, but previously unexplored, role of SMC BMAL1 in AAA. Moreover, these results identify TIMP4 as a novel target of BMAL1, which may mediate the AAA protective effect of SMC BMAL1 deletion. © 2018 American Heart Association, Inc.

Surgery insight: advances in endovascular repair of abdominal aortic aneurysms.

PubMed

Baril, Donald T; Jacobs, Tikva S; Marin, Michael L

2007-04-01

Despite improvements in diagnostic and therapeutic methods and an increased awareness of their clinical significance, abdominal aortic aneurysms (AAAs) continue to be a major source of morbidity and mortality. Endovascular repair of AAAs, initially described in 1990, offers a less-invasive alternative to conventional open repair. The technology and devices used for endovascular repair of AAAs have progressed rapidly and the approach has proven to be safe and effective in short to midterm investigations. Furthermore, several large trials have demonstrated that elective endovascular repair is associated with lower perioperative morbidity and mortality than open repair. The long-term benefits of endovascular repair relative to open repair, however, continue to be studied. In addition to elective repair, the use of endovascular repair for ruptured AAAs has been increasing, and has been shown to be associated with reduced perioperative morbidity and mortality. Advances in endovascular repair of AAAs, including the development of branched and fenestrated grafts and the use of implantable devices to measure aneurysm-sac pressures following stent-graft deployment, have further broadened the application of the technique and have enhanced postoperative monitoring. Despite these advances, endovascular repair of AAAs remains a relatively novel technique, and further long-term data need to be collected.

m-AAA Complexes Are Not Crucial for the Survival of Arabidopsis Under Optimal Growth Conditions Despite Their Importance for Mitochondrial Translation.

PubMed

Kolodziejczak, Marta; Skibior-Blaszczyk, Renata; Janska, Hanna

2018-05-01

For optimal mitochondrial activity, the mitochondrial proteome must be properly maintained or altered in response to developmental and environmental stimuli. Based on studies of yeast and humans, one of the key players in this control are m-AAA proteases, mitochondrial inner membrane-bound ATP-dependent metalloenzymes. This study focuses on the importance of m-AAA proteases in plant mitochondria, providing their first experimentally proven physiological substrate. We found that the Arabidopsis m- AAA complexes composed of AtFTSH3 and/or AtFTSH10 are involved in the proteolytic maturation of ribosomal subunit L32. Consequently, in the double Arabidopsis ftsh3/10 mutant, mitoribosome biogenesis, mitochondrial translation and functionality of OXPHOS (oxidative phosphorylation) complexes are impaired. However, in contrast to their mammalian or yeast counterparts, plant m-AAA complexes are not critical for the survival of Arabidopsis under optimal conditions; ftsh3/10 plants are only slightly smaller in size at the early developmental stage compared with plants containing m-AAA complexes. Our data suggest that a lack of significant visible morphological alterations under optimal growth conditions involves mechanisms which rely on existing functional redundancy and induced functional compensation in Arabidopsis mitochondria.

Persistent type II endoleak after EVAR: the predictive value of the AAA thrombus volume.

PubMed

Gallitto, Enrico; Gargiulo, Mauro; Mascoli, Chiara; Freyrie, Antonio; DE Matteis, Massimo; Serra, Carla; Bianchini Massoni, Claudio; Faggioli, Gianluca; Stella, Andrea

2018-02-01

Persistent type II endoleaks (ELIIp, ≥6 months) after an endovascular aneurysm repair (EVAR) can be associated with adverse outcomes. The aims of this study are the evaluation of the incidence of ELIIp, their preoperative morphological predictive features (PMF) and the post-EVAR abdominal aortic aneurysm (AAA) evolution in the presence of ELIIp. Patients underwent EVAR between 2008 and 2010 were prospectively collected. Cases with ELIIp (group A: AG) were identified. A control group without ELIIp (group B: BG), homogeneous for clinical characteristics, follow-up timing and methods (CTA and/or CEUS at 6.12 months and yearly thereafter) was retrospectively selected. The PMF evaluated by computed-tomography-angiography (CTA) were: AAA-diameter, number and diameter of AAA efferent patent vessels (EPV), AAA-total volume (TV), AAA-thrombus volume (THV) and TV/THV rate (%VR). Volumes were calculated by the dedicated vessels analysis software. AG and BG were compared. The primary endpoint was to evaluate the incidence of ELIIp. Secondary endpoints were to analyze the relation between PMF and ELIIp and to assess the post-EVAR AAA-evolution in the presence of ELIIp. Between 2008 and 2010, 200 patients underwent EVAR to treat AAA electively. An ELIIp was detected in 35cases (17.5%) (AG). Twenty-seven patients (13.5%) were included in BG. An overall of 62 patients (GA+GB) were analyzed. The mean pre-operative AAA diameter and EPV were 58±11.6 mm and 5.5±1.8 mm, respectively. The mean TV and THV were 187±111.5 cc and 82±75 cc, respectively. The median %VR was 42.3%. ELIIp was correlated to EPV≥6 (χ2, p=.015) and %VR <40% (logistic regression, P=0.032). The mean follow-up was 22±9 months. Seven (20%) ELIIp spontaneously sealed and 6 (17%) required reinterventions (2 conversions to OR). There were not PMF associated to ELIIp evolution and AAA growth post-EVAR. ELIIp is a not rare complication and it could require re-interventions. Our data suggest that VEP≥6 or %VT<40% are risk factors for ELIIp. No PMF was able to predict the ELIIp evolution. The relative high rate of re-interventions, could suggest the need of adjunctive/preventing primary procedures in patients at high-risk for ELIIp.

Prophylactic Residual Aneurysmal Sac Embolization with Expandable Hydrogel Embolic Devices for Endoleak Prevention: Preliminary Study in Dogs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hiraki, Takao; Pavcnik, Dusan, E-mail: pavcnikd@ohsu.edu; Uchida, Barry T.

2005-05-15

Objective. To explore the feasibility and efficacy of residual aneurysmal sac (RAS) embolization with the expandable hydrogel embolic device (EHED) in prevention of endoleaks in a surgically created and endoluminally treated abdominal aortic aneurysm (AAA). Methods. In eight dogs, an AAA was created by means of side-to-side anastomosis between the infrarenal abdominal aorta and inferior vena cava (IVC) with ligation of the IVC above and below the anastomotic end, followed by deployment of an endograft with holes. The RAS was then embolized with the EHED. One animal was killed immediately after RAS embolization and one animal died 12 hr aftermore » the procedure. Follow-up aortograms were obtained in six animals after 1 day (1 animal), 2 weeks and 6 months (1 animal), and 8 weeks (4 animals). Results. Four animals had no endoleaks on the follow-up aortograms. The remaining two animals with incomplete RAS embolization had moderate type III endoleaks. Type I or II endoleaks were not seen in any animals. Complications included RAS wall penetration by the devices with platinum wires in two animals (nos. 1 and 2), device migration into an aortic circulation through the endograft holes in two animals (nos. 2 and 3) or through distal interstices between the aortic wall and endograft in one animal (no. 8), aortic occlusion in three animals (nos. 3, 7, and 8), and RAS rupture in one animal (no. 7). Histologic examination showed expanded hydrogels occupying the RAS with associated mature or immature organized thrombus, fibrinous thrombus, or degenerate blood cells. Conclusion. RAS embolization was feasible with the EHED, although additional modifications to the device are required to avoid complications. Angiographic and histologic results suggested that RAS embolization with the EHED may help in the prevention of endoleaks.« less

Stress failure of pulmonary capillaries: role in lung and heart disease

NASA Technical Reports Server (NTRS)

West, J. B.; Mathieu-Costello, O.

1992-01-01

Pulmonary capillaries have extremely thin walls to allow rapid exchange of respiratory gases across them. Recently it has been shown that the wall stresses become very large when the capillary pressure is raised, and in anaesthetised rabbits, ultrastructural damage to the walls is seen at pressures of 40 mm Hg and above. The changes include breaks in the capillary endothelial layer, alveolar epithelial layer, and sometimes all layers of the wall. The strength of the thin part of the capillary wall can be attributed to the type IV collagen in the extracellular matrix. Stress failure of pulmonary capillaries results in a high-permeability form of oedema, or even frank haemorrhage, and is apparently the mechanism of neurogenic pulmonary oedema and high-altitude pulmonary oedema. It also explains the exercise-induced pulmonary haemorrhage that occurs in all racehorses. Several features of mitral stenosis are consistent with stress failure. Overinflation of the lung also leads to stress failure, a common cause of increased capillary permeability in the intensive care environment. Stress failure also occurs if the type IV collagen of the capillary wall is weakened by autoantibodies as in Goodpasture's syndrome. Neutrophil elastase degrades type IV collagen and this may be the starting point of the breakdown of alveolar walls that is characteristic of emphysema. Stress failure of pulmonary capillaries is a hitherto overlooked and potentially important factor in lung and heart disease.

Financial Impact of PEVAR Compared With Standard Endovascular Repair in Canadian Hospitals.

PubMed

Roche-Nagle, Graham; Hazel, Maureen; Rajan, Dheeraj K

2018-05-01

The percutaneous endovascular abdominal aortic repair (PEVAR) approach is a minimally invasive technique that has demonstrated clinical benefit over traditional surgical cut down associated with standard endovascular abdominal aortic aneurysm (AAA) repair (EVAR). The objective of our study was to evaluate the budget impact to a Canadian hospital of changing the technique for AAA repair from the EVAR approach to the PEVAR approach. We examined the budget impact of replacing the EVAR approach with the PEVAR approach in a Canadian hospital that performs 100 endovascular AAA repairs annually. The model incorporates the costs associated with surgery, length of stay, and postoperative complications occurring within 30 days. The use of PEVAR in AAA repair is associated with increased access device costs when compared with the EVAR approach (CAD$1000 vs CAD$400). However, AAA repair completed with the PEVAR approach demonstrates reduced operating time (101 minutes vs 133 minutes), length of stay (2.2 days vs 3.5 days), time in the recovery room (174 minutes vs 193 minutes), and postoperative complications (6% vs 30%), which offset the increased device costs. The model establishes that switching to the PEVAR approach in a Canadian hospital performing 100 AAA repairs annually would result in a potential cost avoidance of CAD$245,120. A change in AAA repair technique from EVAR to PEVAR can be a cost-effective solution for Canadian hospitals. Copyright © 2017 Canadian Association of Radiologists. Published by Elsevier Inc. All rights reserved.

Point Mutations in the Stem Region and the Fourth AAA Domain of Cytoplasmic Dynein Heavy Chain Partially Suppress the Phenotype of NUDF/LIS1 Loss in Aspergillus nidulans

PubMed Central

Zhuang, Lei; Zhang, Jun; Xiang, Xin

2007-01-01

Cytoplasmic dynein performs multiple cellular tasks but its regulation remains unclear. The dynein heavy chain has a N-terminal stem that binds to other subunits and a C-terminal motor unit that contains six AAA (ATPase associated with cellular activities) domains and a microtubule-binding site located between AAA4 and AAA5. In Aspergillus nidulans, NUDF (a LIS1 homolog) functions in the dynein pathway, and two nudF6 partial suppressors were mapped to the nudA dynein heavy chain locus. Here we identified these two mutations. The nudAL1098F mutation resides in the stem region, and nudAR3086C is in the end of AAA4. These mutations partially suppress the phenotype of nudF deletion but do not suppress the phenotype exhibited by mutants of dynein intermediate chain and Arp1. Surprisingly, the stronger ΔnudF suppressor, nudAR3086C, causes an obvious decrease in the basal level of dynein's ATPase activity and an increase in dynein's distribution along microtubules. Thus, suppression of the ΔnudF phenotype may result from mechanisms other than simply the enhancement of dynein's ATPase activity. The fact that a mutation in the end of AAA4 negatively regulates dynein's ATPase activity but partially compensates for NUDF loss indicates the importance of the AAA4 domain in dynein regulation in vivo. PMID:17237507

PM2.5 promotes abdominal aortic aneurysm formation in angiotensin Ⅱ-infused apoe-/- mice.

PubMed

Jun, Xie; Jin, Geng; Fu, Chen; Jinxuan, Zhao; Xuelin, Li; Jiaxin, Hu; Shuaihua, Qiao; Anqi, Shan; Jianzhou, Chen; Lian, Zhou; Xiwen, Zhang; Baoli, Zhu; Biao, Xu

2018-08-01

Particulate matter 2.5 (PM2.5) has proven to be associated with morbidity and mortality from cardiovascular diseases. However, whether PM2.5 could promote the formation of abdominal aortic aneurysm (AAA) is unclear. Present study aimed to explore the relationship between PM2.5 exposure and AAA development. Ang Ⅱ-infused apoe -/- mice were treated with PM2.5 or saline by intranasal instillation. Four weeks later, histological and immunohistological analyses were used to evaluate the effect of PM2.5 on AAA formation. Human aortic smooth muscle cells (HASMCs) were also employed to further analyze the adverse effect of PM2.5 in vitro. We found that PM2.5 could significantly increase the AAA incidence, the maximal abdominal aortic diameter and could promote the degradation of elastin. Additionally, the expression of senescence markers, P21 and P16 were also enhanced after PM2.5 exposure. We also found that PM2.5 significantly increased the AAA related pathological changes, MMP2 and MCP-1 expression in HASMCs. Meanwhile, PM2.5 could increase the expression of senescence markers P21, P16 and SA-β-gal activity, also the reactive oxygen species levels in vitro. PM2.5 promoted the formation of AAA in an Ang Ⅱ-induced AAA model. The underlying mechanism might be cellular senescence after PM2.5 exposure. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

A methodology for developing anisotropic AAA phantoms via additive manufacturing.

PubMed

Ruiz de Galarreta, Sergio; Antón, Raúl; Cazón, Aitor; Finol, Ender A

2017-05-24

An Abdominal Aortic Aneurysm (AAA) is a permanent focal dilatation of the abdominal aorta at least 1.5 times its normal diameter. The criterion of maximum diameter is still used in clinical practice, although numerical studies have demonstrated the importance of biomechanical factors for rupture risk assessment. AAA phantoms could be used for experimental validation of the numerical studies and for pre-intervention testing of endovascular grafts. We have applied multi-material 3D printing technology to manufacture idealized AAA phantoms with anisotropic mechanical behavior. Different composites were fabricated and the phantom specimens were characterized by biaxial tensile tests while using a constitutive model to fit the experimental data. One composite was chosen to manufacture the phantom based on having the same mechanical properties as those reported in the literature for human AAA tissue; the strain energy and anisotropic index were compared to make this choice. The materials for the matrix and fibers of the selected composite are, respectively, the digital materials FLX9940 and FLX9960 developed by Stratasys. The fiber proportion for the composite is equal to 0.15. The differences between the composite behavior and the AAA tissue are small, with a small difference in the strain energy (0.4%) and a maximum difference of 12.4% in the peak Green strain ratio. This work represents a step forward in the application of 3D printing technology for the manufacturing of AAA phantoms with anisotropic mechanical behavior. Copyright © 2017 Elsevier Ltd. All rights reserved.

Clustering behavior in microbial communities from acute endodontic infections.

PubMed

Montagner, Francisco; Jacinto, Rogério C; Signoretti, Fernanda G C; Sanches, Paula F; Gomes, Brenda P F A

2012-02-01

Acute endodontic infections harbor heterogeneous microbial communities in both the root canal (RC) system and apical tissues. Data comparing the microbial structure and diversity in endodontic infections in related ecosystems, such as RC with necrotic pulp and acute apical abscess (AAA), are scarce in the literature. The aim of this study was to examine the presence of selected endodontic pathogens in paired samples from necrotic RC and AAA using polymerase chain reaction (PCR) followed by the construction of cluster profiles. Paired samples of RC and AAA exudates were collected from 20 subjects and analyzed by PCR for the presence of selected strict and facultative anaerobic strains. The frequency of species was compared between the RC and the AAA samples. A stringent neighboring clustering algorithm was applied to investigate the existence of similar high-order groups of samples. A dendrogram was constructed to show the arrangement of the sample groups produced by the hierarchical clustering. All samples harbored bacterial DNA. Porphyromonas endodontalis, Prevotella nigrescens, Filifactor alocis, and Tannerela forsythia were frequently detected in both RC and AAA samples. The selected anaerobic species were distributed in diverse small bacteria consortia. The samples of RC and AAA that presented at least one of the targeted microorganisms were grouped in small clusters. Anaerobic species were frequently detected in acute endodontic infections and heterogeneous microbial communities with low clustering behavior were observed in paired samples of RC and AAA. Copyright © 2012. Published by Elsevier Inc.

Interaction between a normal shock wave and a turbulent boundary layer at high transonic speeds. Part 2: Wall shear stress

NASA Technical Reports Server (NTRS)

Liou, M. S.; Adamson, T. C., Jr.

1979-01-01

An analysis is presented of the flow in the two inner layers, the Reynolds stress sublayer and the wall layer. Included is the calculation of the shear stress at the wall in the interaction region. The limit processes considered are those used for an inviscid flow.

Effect of exercise on hemodynamic conditions in the abdominal aorta.

PubMed

Taylor, C A; Hughes, T J; Zarins, C K

1999-06-01

The beneficial effect of exercise in the retardation of the progression of cardiovascular disease is hypothesized to be caused, at least in part, by the elimination of adverse hemodynamic conditions, including flow recirculation and low wall shear stress. In vitro and in vivo investigations have provided qualitative and limited quantitative information on flow patterns in the abdominal aorta and on the effect of exercise on the elimination of adverse hemodynamic conditions. We used computational fluid mechanics methods to examine the effects of simulated exercise on hemodynamic conditions in an idealized model of the human abdominal aorta. A three-dimensional computer model of a healthy human abdominal aorta was created to simulate pulsatile aortic blood flow under conditions of rest and graded exercise. Flow velocity patterns and wall shear stress were computed in the lesion-prone infrarenal aorta, and the effects of exercise were determined. A recirculation zone was observed to form along the posterior wall of the aorta immediately distal to the renal vessels under resting conditions. Low time-averaged wall shear stress was present in this location, along the posterior wall opposite the superior mesenteric artery and along the anterior wall between the superior and inferior mesenteric arteries. Shear stress temporal oscillations, as measured with an oscillatory shear index, were elevated in these regions. Under simulated light exercise conditions, a region of low wall shear stress and high oscillatory shear index remained along the posterior wall immediately distal to the renal arteries. Under simulated moderate exercise conditions, all the regions of low wall shear stress and high oscillatory shear index were eliminated. This numeric investigation provided detailed quantitative data on the effect of exercise on hemodynamic conditions in the abdominal aorta. Our results indicated that moderate levels of lower limb exercise are necessary to eliminate the flow reversal and regions of low wall shear stress in the abdominal aorta that exist under resting conditions. The lack of flow reversal and increased wall shear stress during exercise suggest a mechanism by which exercise may promote arterial health, namely with the elimination of adverse hemodynamic conditions.

26 CFR 1.1368-3 - Examples.

Code of Federal Regulations, 2010 CFR

2010-04-01

... date. On March 1, 2001, S makes a distribution of $38 to A. The balance in Corporation S's AAA is $100... stock and debt to $0. Under § 1.1368-2(a)(3), S's AAA as of December 31, 1997, has a deficit of $150 as... distributes $110 to B. The balance in the AAA (negative $150 from 1997) is increased by $220 for S's income...

Measurement of Wall Shear Stress in High Speed Air Flow Using Shear-Sensitive Liquid Crystal Coating.

PubMed

Zhao, Jisong

2018-05-17

Wall shear stress is an important quantity in fluid mechanics, but its measurement is a challenging task. An approach to measure wall shear stress vector distribution using shear-sensitive liquid crystal coating (SSLCC) is described. The wall shear stress distribution on the test surface beneath high speed jet flow is measured while using the proposed technique. The flow structures inside the jet flow are captured and the results agree well with the streakline pattern that was visualized using the oil-flow technique. In addition, the shock diamonds inside the supersonic jet flow are visualized clearly using SSLCC and the results are compared with the velocity contour that was measured using the particle image velocimetry (PIV) technique. The work of this paper demonstrates the application of SSLCC in the measurement/visualization of wall shear stress in high speed flow.

Measurement of Wall Shear Stress in High Speed Air Flow Using Shear-Sensitive Liquid Crystal Coating

PubMed Central

Zhao, Jisong

2018-01-01

Wall shear stress is an important quantity in fluid mechanics, but its measurement is a challenging task. An approach to measure wall shear stress vector distribution using shear-sensitive liquid crystal coating (SSLCC) is described. The wall shear stress distribution on the test surface beneath high speed jet flow is measured while using the proposed technique. The flow structures inside the jet flow are captured and the results agree well with the streakline pattern that was visualized using the oil-flow technique. In addition, the shock diamonds inside the supersonic jet flow are visualized clearly using SSLCC and the results are compared with the velocity contour that was measured using the particle image velocimetry (PIV) technique. The work of this paper demonstrates the application of SSLCC in the measurement/visualization of wall shear stress in high speed flow. PMID:29772822

Support for chemistry symposia at the 2011 American Association for the Advancement of Science meeting, February 17-21 2011

DOE Office of Scientific and Technical Information (OSTI.GOV)

Charles Casey

2011-08-20

This proposal supported Chemistry Symposia at the 2011 American Association for the Advancement of Science (AAAS) Meeting in Washington, DC February 17-21, 2011. The Chemistry Section of AAAS presented an unusually strong set of symposia for the 2011 AAAS meeting to help celebrate the 2011 International Year of Chemistry. The AAAS meeting provided an unusual opportunity to convey the excitement and importance of chemistry to a very broad audience and allowed access to a large contingent of the scientific press. Excellent suggestions for symposia were received from AAAS Chemistry Fellows and from the chairs of the American Chemical Society Technicalmore » Divisions. The AAAS Chemistry executive committee selected topics that would have wide appeal to scientists, the public, and the press for formal proposals of symposia. The symposia proposals were peer reviewed by AAAS. The Chemistry Section made a strong case to the program selection committee for approval of the chemistry symposia and 6 were approved for the 2011 annual meeting. The titles of the approved symposia were: (1) Powering the Planet: Generation of Clean Fuels from Sunlight and Water, (2) Biological Role and Consequences of Intrinsic Protein Disorder, (3) Chemically Speaking: How Organisms Talk to Each Other, (4) Molecular Self-Assembly and Artificial Molecular Machines, (5) Frontiers in Organic Materials for Information Processing, Energy and Sensors, and (6) Celebrating Marie Curie's 100th Anniversary of Her Nobel Prize in Chemistry. The Chemistry Section of AAAS is provided with funds to support only 1-2 symposia a year. Because of the much greater number of symposia approved in conjunction with observance of the 2011 International Year of Chemistry, additional support was sought from DOE to help support the 30 invited speakers and 8 symposia moderators/organizers. Support for the symposia provided the opportunity to highlight the excitement of current chemical research, to educate the public about the achievements of chemistry and its contributions to the well-being of humankind. The 2011 AAAS Annual Meeting provided an important opportunity to play a prominent role in the global celebration of the 2011 International Year of Chemistry.« less

Sex differences in mortality after abdominal aortic aneurysm repair in the UK

PubMed Central

Saratzis, A.; Sweeting, M. J.; Michaels, J.; Powell, J. T.; Thompson, S. G.; Bown, M. J.

2017-01-01

Background The UK abdominal aortic aneurysm (AAA) screening programmes currently invite only men for screening because the benefit in women is uncertain. Perioperative risk is critical in determining the effectiveness of screening, and contemporary estimates of these risks in women are lacking. The aim of this study was to compare mortality following AAA repair between women and men in the UK. Methods Anonymized data from the UK National Vascular Registry (NVR) for patients undergoing AAA repair (January 2010 to December 2014) were analysed. Co‐variables were extracted for analysis by sex. The primary outcome measure was in‐hospital mortality. Secondary outcome measures included mortality by 5‐year age groups and duration of hospital stay. Logistic regression was performed to adjust for age, calendar time, AAA diameter and smoking status. NVR‐based outcomes were checked against Hospital Episode Statistics (HES) data. Results A total of 23 245 patients were included (13·0 per cent women). Proportionally, more women than men underwent open repair. For elective open AAA repair, the in‐hospital mortality rate was 6·9 per cent in women and 4·0 per cent in men (odds ratio (OR) 1·48, 95 per cent c.i. 1·08 to 2·02; P = 0·014), whereas for elective endovascular AAA repair it was 1·8 per cent in women and 0·7 per cent in men (OR 2·86, 1·72 to 4·74; P < 0·001); the results in HES were similar. For ruptured AAA, there was no sex difference in mortality within the NVR; however, in HES, for ruptured open AAA repair, the in‐hospital mortality rate was higher in women (33·6 versus 27·1 per cent; OR 1·36, 1·16 to 1·59; P < 0·001). Conclusion Women have a higher in‐hospital mortality rate than men after elective AAA repair even after adjustment. This higher mortality may have an impact on the benefit offered by any screening programme offered to women. PMID:28745403

How Quickly Do Asymptomatic Infrarenal Abdominal Aortic Aneurysms Grow and What Factors Affect Aneurysm Growth Rates? Analysis of a Single Centre Surveillance Cohort Database.

PubMed

Ahmad, Mehtab; Mistry, Rakesh; Hodson, James; Bradbury, Andrew W

2017-11-01

Abdominal aortic aneurysm (AAA) maximum antero-posterior diameter (MAPD) is the parameter most commonly used to inform the timing of surgical intervention. However, other factors, such as growth rates and patient comorbidities are likely to be important considerations as they may influence AAA related complications including rupture, operative outcomes, and the clinical and cost effectiveness of continued surveillance. This was a retrospective analysis of a 20 year period of a single centre AAA surveillance database. In total, 5363 AAA measurements in 692 patients were analysed for patient demographics, including comorbidity and drug history, growth and rupture rates, and cause of death. A significant proportion of patients (n = 73; 11%) were kept under surveillance despite having a MAPD < 30 mm. Overall, mean aneurysm growth rate was 2.3 mm/year. Elective repair was undertaken in 20.1% and those who required surgical intervention had significantly faster growth rates. Only 3.9% of patients in surveillance ruptured, 40.7% of whom had a MAPD <55 mm at their last scan. Of the 214 deaths recorded, only 11.7% were related to AAA. The majority of patients who died in surveillance did so from malignancy. Patients with larger AAA (MAPD > 40 mm) on entry into surveillance were significantly more likely to receive surgical intervention, as were those whose AAA expanded >4 mm/year. Females had significantly higher growth rates, and those with diabetes had significantly smaller growth rates. Other comorbidities and drug history were not associated with AAA growth, or 5 and 10 year surgery free survival. The results highlight several areas for service improvement. Specifically, it is important not to maintain surveillance in patients who are very unlikely to ever grow to a point where AAA surgery would be contemplated on grounds or age and/or comorbidity. Similarly, patients should be discharged from surveillance when this likelihood becomes apparent. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Breaking symmetry in non-planar bifurcations: distribution of flow and wall shear stress.

PubMed

Lu, Yiling; Lu, Xiyun; Zhuang, Lixian; Wang, Wen

2002-01-01

Non-planarity in blood vessels is known to influence arterial flows and wall shear stress. To gain insight, computational fluid dynamics (CFD) has been used to investigate effects of curvature and out-of-plane geometry on the distribution of fluid flows and wall shear stresses in a hypothetical non-planar bifurcation. Three-dimensional Navier-Stokes equations for a steady state Newtonian fluid were solved numerically using a finite element method. Non-planarity in one of the two daughter vessels is found to deflect flow from the inner wall of the vessel to the outer wall and to cause changes in the distribution of wall shear stresses. Results from this study agree to experimental observations and CFD simulations in the literature, and support the view that non-planarity in blood vessels is a factor with important haemodynamic significance and may play a key role in vascular biology and pathophysiology.

Spatio-temporal characteristics of large scale motions in a turbulent boundary layer from direct wall shear stress measurement

NASA Astrophysics Data System (ADS)

Pabon, Rommel; Barnard, Casey; Ukeiley, Lawrence; Sheplak, Mark

2016-11-01

Particle image velocimetry (PIV) and fluctuating wall shear stress experiments were performed on a flat plate turbulent boundary layer (TBL) under zero pressure gradient conditions. The fluctuating wall shear stress was measured using a microelectromechanical 1mm × 1mm floating element capacitive shear stress sensor (CSSS) developed at the University of Florida. The experiments elucidated the imprint of the organized motions in a TBL on the wall shear stress through its direct measurement. Spatial autocorrelation of the streamwise velocity from the PIV snapshots revealed large scale motions that scale on the order of boundary layer thickness. However, the captured inclination angle was lower than that determined using the classic method by means of wall shear stress and hot-wire anemometry (HWA) temporal cross-correlations and a frozen field hypothesis using a convection velocity. The current study suggests the large size of these motions begins to degrade the applicability of the frozen field hypothesis for the time resolved HWA experiments. The simultaneous PIV and CSSS measurements are also used for spatial reconstruction of the velocity field during conditionally sampled intense wall shear stress events. This material is based upon work supported by the National Science Foundation Graduate Research Fellowship under Grant No. DGE-1315138.

Wall shear stress estimates in coronary artery constrictions

NASA Technical Reports Server (NTRS)

Back, L. H.; Crawford, D. W.

1992-01-01

Wall shear stress estimates from laminar boundary layer theory were found to agree fairly well with the magnitude of shear stress levels along coronary artery constrictions obtained from solutions of the Navier Stokes equations for both steady and pulsatile flow. The relatively simple method can be used for in vivo estimates of wall shear stress in constrictions by using a vessel shape function determined from a coronary angiogram, along with a knowledge of the flow rate.

Abdominal aortic aneurysm with periaortic malignant lymphoma differentiated from aneurysmal rupture by clinical presentation and magnetic resonance imaging.

PubMed

Kamata, Sokichi; Itou, Yoshito; Idoguchi, Koji; Imakita, Masami; Funatsu, Toshihiro; Yagihara, Toshikatsu

2018-06-01

Abdominal aortic aneurysm (AAA) associated with periaortic malignant lymphoma is difficult to differentiate from aneurysmal rupture because of similarities in their clinical presentation and appearance on computed tomography images. We here report a case of AAA associated with periaortic malignant lymphoma diagnosed preoperatively with an absence of typical symptoms, showing that AAA in periaortic malignant lymphoma can present without any clinical correlates. Magnetic resonance imaging was used to confirm the diagnosis. The patient was treated by endovascular repair, which may be safer and more effective than open surgery for AAA associated with malignant lymphoma because of the tight adhesion between the aneurysm and the lymphoid tissue.

Experimental study of the flow in the wake of a stationary sphere immersed in a turbulent boundary layer

NASA Astrophysics Data System (ADS)

van Hout, René; Eisma, Jerke; Elsinga, Gerrit E.; Westerweel, Jerry

2018-02-01

In many applications, finite-sized particles are immersed in a turbulent boundary layer (TBL) and it is of interest to study wall effects on the instantaneous shedding of turbulence structures and associated mean velocity and Reynolds stress distributions. Here, 3D flow field dynamics in the wake of a prototypical, small sphere (D+=50 , 692

Cell Wall Remodeling Enzymes Modulate Fungal Cell Wall Elasticity and Osmotic Stress Resistance.

PubMed

Ene, Iuliana V; Walker, Louise A; Schiavone, Marion; Lee, Keunsook K; Martin-Yken, Hélène; Dague, Etienne; Gow, Neil A R; Munro, Carol A; Brown, Alistair J P

2015-07-28

The fungal cell wall confers cell morphology and protection against environmental insults. For fungal pathogens, the cell wall is a key immunological modulator and an ideal therapeutic target. Yeast cell walls possess an inner matrix of interlinked β-glucan and chitin that is thought to provide tensile strength and rigidity. Yeast cells remodel their walls over time in response to environmental change, a process controlled by evolutionarily conserved stress (Hog1) and cell integrity (Mkc1, Cek1) signaling pathways. These mitogen-activated protein kinase (MAPK) pathways modulate cell wall gene expression, leading to the construction of a new, modified cell wall. We show that the cell wall is not rigid but elastic, displaying rapid structural realignments that impact survival following osmotic shock. Lactate-grown Candida albicans cells are more resistant to hyperosmotic shock than glucose-grown cells. We show that this elevated resistance is not dependent on Hog1 or Mkc1 signaling and that most cell death occurs within 10 min of osmotic shock. Sudden decreases in cell volume drive rapid increases in cell wall thickness. The elevated stress resistance of lactate-grown cells correlates with reduced cell wall elasticity, reflected in slower changes in cell volume following hyperosmotic shock. The cell wall elasticity of lactate-grown cells is increased by a triple mutation that inactivates the Crh family of cell wall cross-linking enzymes, leading to increased sensitivity to hyperosmotic shock. Overexpressing Crh family members in glucose-grown cells reduces cell wall elasticity, providing partial protection against hyperosmotic shock. These changes correlate with structural realignment of the cell wall and with the ability of cells to withstand osmotic shock. The C. albicans cell wall is the first line of defense against external insults, the site of immune recognition by the host, and an attractive target for antifungal therapy. Its tensile strength is conferred by a network of cell wall polysaccharides, which are remodeled in response to growth conditions and environmental stress. However, little is known about how cell wall elasticity is regulated and how it affects adaptation to stresses such as sudden changes in osmolarity. We show that elasticity is critical for survival under conditions of osmotic shock, before stress signaling pathways have time to induce gene expression and drive glycerol accumulation. Critical cell wall remodeling enzymes control cell wall flexibility, and its regulation is strongly dependent on host nutritional inputs. We also demonstrate an entirely new level of cell wall dynamism, where significant architectural changes and structural realignment occur within seconds of an osmotic shock. Copyright © 2015 Ene et al.

Extremely high wall-shear stress events in a turbulent boundary layer

NASA Astrophysics Data System (ADS)

Pan, Chong; Kwon, Yongseok

2018-04-01

The present work studies the fluctuating characteristics of the streamwise wall-shear stress in a DNS of a turbulent boundary layer at Re τ =1500 from a structural view. The two-dimensional field of the fluctuating friction velocity u‧ τ (x,z) is decomposed into the large- and small-scale components via a recently proposed scale separation algorithm, Quasi-bivariate Variational Mode Decomposition (QB-VMD). Both components are found to be dominated by streak-like structures, which can be regarded as the wall signature of the inner-layer streaks and the outer-layer LSMs, respectively. Extreme positive/negative wall-shear stress fluctuation events are detected in the large-scale component. The former’s occurrence frequency is nearly one order of magnitude higher than the latter; therefore, they contribute a significant portion of the long tail of the wall-shear stress distribution. Both two-point correlations and conditional averages show that these extreme positive wall-shear stress events are embedded in the large-scale positive u‧ τ streaks. They seem to be formed by near-wall ‘splatting’ process, which are related to strong finger-like sweeping (Q4) events originated from the outer-layer positive LSMs.

Application of mean wall shear stress boundary condition to complex turbulent flows using a wall-modeled large eddy simulation

NASA Astrophysics Data System (ADS)

Cho, Minjeong; Lee, Jungil; Choi, Haecheon

2012-11-01

The mean wall shear stress boundary condition was successfully applied to turbulent channel and boundary flows using large eddy simulation without resolving near-wall region (see Lee, Cho & Choi in this book of abstracts). In the present study, we apply this boundary condition to more complex flows where flow separation and redeveloping flow exist. As a test problem, we consider flow over a backward-facing step at Reh = 22860 based on the step height. Turbulent boundary layer flow at the inlet (Reθ = 1050) is obtained using inflow generation technique by Lund et al. (1998) but with wall shear stress boundary condition. First, we prescribe the mean wall shear stress distribution obtained from DNS (Kim, 2011, Ph.D. Thesis, Stanford U.) as the boundary condition of present simulation. Here we give no-slip boundary condition at flow-reversal region. The present results are in good agreements with the flow statistics by DNS. Currently, a dynamic approach of obtaining mean wall shear stress based on the log-law is being applied to the flow having flow separation and its results will be shown in the presentation. Supported by the WCU and NRF programs.

Structure of high and low shear-stress events in a turbulent boundary layer

NASA Astrophysics Data System (ADS)

Gomit, G.; de Kat, R.; Ganapathisubramani, B.

2018-01-01

Simultaneous particle image velocimetry (PIV) and wall-shear-stress sensor measurements were performed to study structures associated with shear-stress events in a flat plate turbulent boundary layer at a Reynolds number Reτ≈4000 . The PIV field of view covers 8 δ (where δ is the boundary layer thickness) along the streamwise direction and captures the entire boundary layer in the wall-normal direction. Simultaneously, wall-shear-stress measurements that capture the large-scale fluctuations were taken using a spanwise array of hot-film skin-friction sensors (spanning 2 δ ). Based on this combination of measurements, the organization of the conditional wall-normal and streamwise velocity fluctuations (u and v ) and of the Reynolds shear stress (-u v ) can be extracted. Conditional averages of the velocity field are computed by dividing the histogram of the large-scale wall-shear-stress fluctuations into four quartiles, each containing 25% of the occurrences. The conditional events corresponding to the extreme quartiles of the histogram (positive and negative) predominantly contribute to a change of velocity profile associated with the large structures and in the modulation of the small scales. A detailed examination of the Reynolds shear-stress contribution related to each of the four quartiles shows that the flow above a low wall-shear-stress event carries a larger amount of Reynolds shear stress than the other quartiles. The contribution of the small and large scales to this observation is discussed based on a scale decomposition of the velocity field.

Abdominal aortic feminism.

PubMed

Mortimer, Alice Emily

2014-11-14

A 79-year-old woman presented to a private medical practice 2 years previously for an elective ultrasound screening scan. This imaging provided the evidence for a diagnosis of an abdominal aortic aneurysm (AAA) to be made. Despite having a number of recognised risk factors for an AAA, her general practitioner at the time did not follow the guidance set out by the private medical professional, that is, to refer the patient to a vascular specialist to be entered into a surveillance programme and surgically evaluated. The patient became symptomatic with her AAA, was admitted to hospital and found to have a tender, symptomatic, 6 cm leaking AAA. She consented for an emergency open AAA repair within a few hours of being admitted to hospital, despite the 50% perioperative mortality risk. The patient spent 4 days in intensive care where she recovered well. She was discharged after a 12 day hospital stay but unfortunately passed away shortly after her discharge from a previously undiagnosed gastric cancer. 2014 BMJ Publishing Group Ltd.

The level of aryl acylamidase activity displayed by human butyrylcholinesterase depends on its molecular distribution.

PubMed

Montenegro, M F; Moral-Naranjo, M T; Páez de la Cadena, M; Campoy, F J; Muñoz-Delgado, E; Vidal, C J

2008-09-25

Butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE) display both esterase and aryl acylamidase (AAA) activities. Their AAA activity can be measured using o-nitroacetanilide (ONA). In human samples depleted of acetylcholinesterase, we noticed that the ratio of amidase to esterase activities varied depending on the source, despite both activities being due to BuChE. Searching for an explanation, we compared the activities of BuChE molecular forms in samples of human colon, kidney and serum, and observed that BuChE monomers (G(1)) hydrolyzed o-nitroacetanilide much faster than tetramers (G(4)). This fact suggested that association might cause differences in the AAA site between single and polymerized subunits. This and other post-translational modifications in BuChE subunits probably determine their level of AAA activity. The higher amidase activity of monomers could justify the presence of single BuChE subunits in cells as a way to preserve the AAA activity of BuChE, which could be lost by oligomerization.

Abdominal aortic feminism

PubMed Central

Mortimer, Alice Emily

2014-01-01

A 79-year-old woman presented to a private medical practice 2 years previously for an elective ultrasound screening scan. This imaging provided the evidence for a diagnosis of an abdominal aortic aneurysm (AAA) to be made. Despite having a number of recognised risk factors for an AAA, her general practitioner at the time did not follow the guidance set out by the private medical professional, that is, to refer the patient to a vascular specialist to be entered into a surveillance programme and surgically evaluated. The patient became symptomatic with her AAA, was admitted to hospital and found to have a tender, symptomatic, 6 cm leaking AAA. She consented for an emergency open AAA repair within a few hours of being admitted to hospital, despite the 50% perioperative mortality risk. The patient spent 4 days in intensive care where she recovered well. She was discharged after a 12 day hospital stay but unfortunately passed away shortly after her discharge from a previously undiagnosed gastric cancer. PMID:25398912

Ribosomes slide on lysine-encoding homopolymeric A stretches

PubMed Central

Koutmou, Kristin S; Schuller, Anthony P; Brunelle, Julie L; Radhakrishnan, Aditya; Djuranovic, Sergej; Green, Rachel

2015-01-01

Protein output from synonymous codons is thought to be equivalent if appropriate tRNAs are sufficiently abundant. Here we show that mRNAs encoding iterated lysine codons, AAA or AAG, differentially impact protein synthesis: insertion of iterated AAA codons into an ORF diminishes protein expression more than insertion of synonymous AAG codons. Kinetic studies in E. coli reveal that differential protein production results from pausing on consecutive AAA-lysines followed by ribosome sliding on homopolymeric A sequence. Translation in a cell-free expression system demonstrates that diminished output from AAA-codon-containing reporters results from premature translation termination on out of frame stop codons following ribosome sliding. In eukaryotes, these premature termination events target the mRNAs for Nonsense-Mediated-Decay (NMD). The finding that ribosomes slide on homopolymeric A sequences explains bioinformatic analyses indicating that consecutive AAA codons are under-represented in gene-coding sequences. Ribosome ‘sliding’ represents an unexpected type of ribosome movement possible during translation. DOI: http://dx.doi.org/10.7554/eLife.05534.001 PMID:25695637

Multifunctional Mitochondrial AAA Proteases

PubMed Central

Glynn, Steven E.

2017-01-01

Mitochondria perform numerous functions necessary for the survival of eukaryotic cells. These activities are coordinated by a diverse complement of proteins encoded in both the nuclear and mitochondrial genomes that must be properly organized and maintained. Misregulation of mitochondrial proteostasis impairs organellar function and can result in the development of severe human diseases. ATP-driven AAA+ proteins play crucial roles in preserving mitochondrial activity by removing and remodeling protein molecules in accordance with the needs of the cell. Two mitochondrial AAA proteases, i-AAA and m-AAA, are anchored to either face of the mitochondrial inner membrane, where they engage and process an array of substrates to impact protein biogenesis, quality control, and the regulation of key metabolic pathways. The functionality of these proteases is extended through multiple substrate-dependent modes of action, including complete degradation, partial processing, or dislocation from the membrane without proteolysis. This review discusses recent advances made toward elucidating the mechanisms of substrate recognition, handling, and degradation that allow these versatile proteases to control diverse activities in this multifunctional organelle. PMID:28589125

Multifunctional Mitochondrial AAA Proteases.

PubMed

Glynn, Steven E

2017-01-01

Mitochondria perform numerous functions necessary for the survival of eukaryotic cells. These activities are coordinated by a diverse complement of proteins encoded in both the nuclear and mitochondrial genomes that must be properly organized and maintained. Misregulation of mitochondrial proteostasis impairs organellar function and can result in the development of severe human diseases. ATP-driven AAA+ proteins play crucial roles in preserving mitochondrial activity by removing and remodeling protein molecules in accordance with the needs of the cell. Two mitochondrial AAA proteases, i-AAA and m-AAA, are anchored to either face of the mitochondrial inner membrane, where they engage and process an array of substrates to impact protein biogenesis, quality control, and the regulation of key metabolic pathways. The functionality of these proteases is extended through multiple substrate-dependent modes of action, including complete degradation, partial processing, or dislocation from the membrane without proteolysis. This review discusses recent advances made toward elucidating the mechanisms of substrate recognition, handling, and degradation that allow these versatile proteases to control diverse activities in this multifunctional organelle.

Optical microangiography reveals collateral blood perfusion dynamics in mouse cerebral cortex after focal stroke

NASA Astrophysics Data System (ADS)

Baran, Utku; Li, Yuandong; Wang, Ruikang K.

2015-03-01

Arteriolo-arteriolar anastomosis's role in regulating blood perfusion through penetrating arterioles during stroke is yet to be discovered. We apply ultra-high sensitive optical microangiography (UHS-OMAG) and Doppler optical microangiography (DOMAG) techniques to evaluate vessel diameter and red blood cell velocity changes in large number of pial and penetrating arterioles in relation with arteriolo-arteriolar anastomosis (AAA) during and after focal stroke. Thanks to the high sensitivity of UHS-OMAG, we were able to image pial microvasculature up to capillary level through a cranial window (9 mm2), and DOMAG provided clear image of penetrating arterioles up to 500μm depth. Results showed that penetrating arterioles close to a strong AAA connection dilate whereas penetrating arterioles constrict significantly in weaker AAA regions. These results suggest that AAA plays a major role in active regulation of the pial arterioles, and weaker AAA connections lead to poor blood perfusion to penumbra through penetrating arterioles.

Sustained expression of MCP-1 by low wall shear stress loading concomitant with turbulent flow on endothelial cells of intracranial aneurysm.

PubMed

Aoki, Tomohiro; Yamamoto, Kimiko; Fukuda, Miyuki; Shimogonya, Yuji; Fukuda, Shunichi; Narumiya, Shuh

2016-05-09

Enlargement of a pre-existing intracranial aneurysm is a well-established risk factor of rupture. Excessive low wall shear stress concomitant with turbulent flow in the dome of an aneurysm may contribute to progression and rupture. However, how stress conditions regulate enlargement of a pre-existing aneurysm remains to be elucidated. Wall shear stress was calculated with 3D-computational fluid dynamics simulation using three cases of unruptured intracranial aneurysm. The resulting value, 0.017 Pa at the dome, was much lower than that in the parent artery. We loaded wall shear stress corresponding to the value and also turbulent flow to the primary culture of endothelial cells. We then obtained gene expression profiles by RNA sequence analysis. RNA sequence analysis detected hundreds of differentially expressed genes among groups. Gene ontology and pathway analysis identified signaling related with cell division/proliferation as overrepresented in the low wall shear stress-loaded group, which was further augmented by the addition of turbulent flow. Moreover, expression of some chemoattractants for inflammatory cells, including MCP-1, was upregulated under low wall shear stress with concomitant turbulent flow. We further examined the temporal sequence of expressions of factors identified in an in vitro study using a rat model. No proliferative cells were detected, but MCP-1 expression was induced and sustained in the endothelial cell layer. Low wall shear stress concomitant with turbulent flow contributes to sustained expression of MCP-1 in endothelial cells and presumably plays a role in facilitating macrophage infiltration and exacerbating inflammation, which leads to enlargement or rupture.

Color and opacity of composites protected with surface sealants and submitted to artificial accelerated aging.

PubMed

Aguilar, Fabiano Gamero; Roberti Garcia, Lucas da Fonseca; Cruvinel, Diogo Rodrigues; Sousa, Ana Beatriz Silva; de Carvalho Panzeri Pires-de-Souza, Fernanda

2012-01-01

To evaluate the color similarity, stability and opacity of composites (TPH, Charisma, and Concept, shade A2) protected with surface sealants (Fortify Plus and Biscover) and cyanoacrylate (Super Bonder). Forty specimens of each composite were made and separated into 4 groups (n=10) according to the surface protection: GI - without sealant; GII - cyanoacrylate; GIII - Fortify Plus; GIV - Biscover. Color and opacity readings were taken before and after Artificial Acelerated Aging (AAA) and the values obtained for color stability were submitted to statistical analysis by 2-way ANOVA and Bonferroni's test (P<.05). The values acquired for color similarity were submitted to 1-way ANOVA and Tukey's test (P<.05). The specimen sufaces were compared before and after AAA using Scanning Electronic Microscopy (SEM). Studied composites did not present the same values for the coordinates L*, a* and b * before AAA, indicating that there was no color similarity among them. All composites presented color alteration after AAA with clinically unacceptable values. Protected groups presented lower opacity variation after AAA, in comparison with the control goup. SEM evaluation demonstrated that AAA increased the surface irregularities in all of the studied groups. Surface sealants were not effective in maintaining composite color, but were able to maintain opacity.

Animal models in the research of abdominal aortic aneurysms development.

PubMed

Patelis, N; Moris, D; Schizas, D; Damaskos, C; Perrea, D; Bakoyiannis, C; Liakakos, T; Georgopoulos, S

2017-12-20

Abdominal aortic aneurysm (AAA) is a prevalent and potentially life threatening disease. Many animal models have been developed to simulate the natural history of the disease or test preclinical endovascular devices and surgical procedures. The aim of this review is to describe different methods of AAA induction in animal models and report on the effectiveness of the methods described in inducing an analogue of a human AAA. The PubMed database was searched for publications with titles containing the following terms "animal" or "animal model(s)" and keywords "research", "aneurysm(s)", "aorta", "pancreatic elastase", "Angiotensin", "AngII" "calcium chloride" or "CaCl(2)". Starting date for this search was set to 2004, since previously bibliography was already covered by the review of Daugherty and Cassis (2004). We focused on animal studies that reported a model of aneurysm development and progression. A number of different approaches of AAA induction in animal models has been developed, used and combined since the first report in the 1960's. Although specific methods are successful in AAA induction in animal models, it is necessary that these methods and their respective results are in line with the pathophysiology and the mechanisms involved in human AAA development. A researcher should know the advantages/disadvantages of each animal model and choose the appropriate model.

A nurse-run clinic for patients with incidentally discovered small abdominal aortic aneurysms is feasible and cost-effective.

PubMed

Griffin, J L; Clarke, G A; Roake, J A; Lewis, D R

2015-04-01

Patients with incidentally discovered small abdominal aortic aneurysms (AAA) require assessment by a vascular surgery department for possible enrollment in a surveillance programme. Our unit implemented a vascular nurse-run AAA clinic in October 2010. The aim of this study was to assess the feasibility of a specialist nurse-run small AAA clinic. Demographic and clinical data were collected prospectively for all patients seen in the new vascular nurse clinic between October 2010 and November 2012. A validated AAA operative mortality score was used to aid decision making by the vascular nurse. Some 250 patients were seen in the clinic. 198 (79.2%) patients were enrolled in surveillance, 40 (16%) declined enrollment and 12 (4.8%) were referred to a consultant clinic for further assessment. The majority of patients were male and the mean age was 73.7 years. Co-morbidities included hypertension, a history of cardiovascular disease, and hyperlipidaemia. The majority of referrals were considered to be low operative risk. No aneurysms ruptured whilst under surveillance. A nurse-run clinic that assesses patients with incidentally discovered small AAAs for inclusion in AAA surveillance is a feasible alternative to assessment of these patients in a consultant-run clinic. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

EPA Prevents the Development of Abdominal Aortic Aneurysms through Gpr-120/Ffar-4.

PubMed

Kamata, Ryo; Bumdelger, Batmunkh; Kokubo, Hiroki; Fujii, Masayuki; Yoshimura, Koichi; Ishida, Takafumi; Ishida, Mari; Yoshizumi, Masao

2016-01-01

Abdominal aortic aneurysms (AAAs), which commonly occur among elderly individuals, are accompanied by a risk of rupture with a high mortality rate. Although eicosapentaenoic acid (EPA) has been reported to prevent AAA formation, the mechanism by which EPA works on vascular smooth muscle cells is unknown. This study aimed to investigate the mechanism by which orally-administered EPA prevents the formation of severe AAAs that develop in Osteoprotegerin (Opg) knockout (KO) mice. In the CaCl2-induced AAA model, EPA attenuated the enhanced progression of AAAs in Opg-KO mice, including the increase in aortic diameter with destruction of elastic fibers in the media. Immunohistochemical analyses showed that EPA reduced the phosphorylation of transforming growth factor beta-activated kinase-1/Map3k7 (Tak-1) and c-Jun NH2-terminal kinase (JNK), as well as the expression of Matrix metalloproteinase-9 (Mmp-9) in the media of the aorta. In smooth muscle cell cultures, rh-TRAIL-induced activation of the Tak-1-JNK pathway and increase in Mmp-9 expression were inhibited by EPA. Moreover, GW9508, a specific ligand for G-protein coupled receptor (Gpr)-120/Free fatty acid receptor (Ffar)-4, mimicked the effects of EPA. The effects of EPA were abrogated by knockdown of the Gpr-120/Ffar-4 receptor gene. Our data demonstrate that the Trail-Tak-1-JNK-Mmp-9 pathway is responsible for the enhancement of AAAs in Opg-KO mice, and that EPA inhibits the Tak-1-JNK pathway by activating Gpr-120/Ffar-4, which results in the attenuation of AAA development.

EPA Prevents the Development of Abdominal Aortic Aneurysms through Gpr-120/Ffar-4

PubMed Central

Kamata, Ryo; Bumdelger, Batmunkh; Kokubo, Hiroki; Fujii, Masayuki; Yoshimura, Koichi; Ishida, Takafumi; Ishida, Mari; Yoshizumi, Masao

2016-01-01

Abdominal aortic aneurysms (AAAs), which commonly occur among elderly individuals, are accompanied by a risk of rupture with a high mortality rate. Although eicosapentaenoic acid (EPA) has been reported to prevent AAA formation, the mechanism by which EPA works on vascular smooth muscle cells is unknown. This study aimed to investigate the mechanism by which orally-administered EPA prevents the formation of severe AAAs that develop in Osteoprotegerin (Opg) knockout (KO) mice. In the CaCl2-induced AAA model, EPA attenuated the enhanced progression of AAAs in Opg-KO mice, including the increase in aortic diameter with destruction of elastic fibers in the media. Immunohistochemical analyses showed that EPA reduced the phosphorylation of transforming growth factor beta-activated kinase-1/Map3k7 (Tak-1) and c-Jun NH2-terminal kinase (JNK), as well as the expression of Matrix metalloproteinase-9 (Mmp-9) in the media of the aorta. In smooth muscle cell cultures, rh-TRAIL-induced activation of the Tak-1-JNK pathway and increase in Mmp-9 expression were inhibited by EPA. Moreover, GW9508, a specific ligand for G-protein coupled receptor (Gpr)-120/Free fatty acid receptor (Ffar)-4, mimicked the effects of EPA. The effects of EPA were abrogated by knockdown of the Gpr-120/Ffar-4 receptor gene. Our data demonstrate that the Trail-Tak-1-JNK-Mmp-9 pathway is responsible for the enhancement of AAAs in Opg-KO mice, and that EPA inhibits the Tak-1-JNK pathway by activating Gpr-120/Ffar-4, which results in the attenuation of AAA development. PMID:27764222

Patients with abdominal aortic aneurysm have a high prevalence of popliteal artery aneurysms.

PubMed

Tuveson, Viktoria; Löfdahl, Hedvig E; Hultgren, Rebecka

2016-08-01

Patients with abdominal aortic aneurysms (AAA) are more prone to develop popliteal artery aneurysms (PAA), but the prevalence is not well known. Our aim was to investigate the prevalence of PAA in patients with AAA, and to determine whether a certain risk factor profile is more commonly found in patients with concurrent aneurysms. All AAA patients (ICD code I71.3, I71.4) attending the outpatient clinic at the Karolinska University Hospital between 2011 and 2013 were included in the study cohort (n=465); 48% (225) had been subjected to an ultrasound or computed tomography scan of their popliteal arteries. In these patients, three definitions of PAA were considered (⩾ 10.5, ⩾ 12, ⩾ 15 mm), although the overall analysis is based on PAA ⩾ 12 mm. The mean age was 70.7 years (SD 7.5), 89% were men, and the mean AAA diameter was 47 mm (SD 14). The prevalence of PAA was 19% (n=43) by definition ⩾ 12 mm, and 11% (n=25) with 15 mm. Claudication was more frequently found in AAA patients with PAA than patients without PAA. Sensitivity between clinical examination and radiology was 26%, and the specificity for clinical examination was 90%. In conclusion, owing to the high prevalence of PAA in AAA patients, described by us and others, the low cost and risks associated with ultrasound and the poor sensitivity at clinical examination, all women and men with AAA should undergo one radiological examination of their popliteal arteries. © The Author(s) 2016.

Endovascular strategy for the elective treatment of concomitant aortoiliac aneurysm and symptomatic large bowel diverticular disease.

PubMed

Illuminati, Giulio; Ricco, Jean-Baptiste; Schneider, Fabrice; Caliò, Francesco G; Ceccanei, Gianluca; Pacilè, Maria A; Pizzardi, Giulia; Palumbo, Piergaspare; Vietri, Francesco

2014-07-01

The purpose of this study was to evaluate the strategy for treatment of patients presenting with asymptomatic diverticular disease of the large bowel associated with an asymptomatic aortoiliac aneurysmal (AAA) disease. Sixty-nine patients were included in this retrospective study. The patients were divided into 5 groups according to the type and sequence of the surgical treatment: 32 patients (47%) underwent colectomy followed by a staged open AAA repair (group A); 10 patients (14%) were treated with open AAA repair followed by a staged colectomy (group B); 13 patients (18%) received endovascular aneurysm repair (EVAR) followed by a staged bowel resection (group C); 8 patients (12%) had a bowel resection followed by staged EVAR (group D); and 6 patients (9%) underwent simultaneous open AAA repair and bowel resection (group E). Primary end points were mortality and complications after any of the procedures. Secondary end point was the time interval between the staged procedures. The cumulative death rate for delayed treatment of AAA was 6.5% and 0% for delayed treatment of diverticular disease [P=0.22]. The mean time interval between the staged procedures was 11 days for EVAR/colon resection (group C and group D) and 73 days for open AAA repair/colon resection (group A and group B; P<0.01). EVAR allows a significant reduction in the time required between AAA repair and colon resection, but no definite rule can be established regarding the sequence of staged procedures. Combined procedures should be reserved for selected cases. Copyright © 2014 Elsevier Inc. All rights reserved.

A detailed kinetic mechanism including methanol and nitrogen pollutants relevant to the gas-phase combustion and pyrolysis of biomass-derived fuels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Coda Zabetta, Edgardo; Hupa, Mikko

2008-01-15

A detailed chemical kinetic mechanism for the simulation of the gas-phase combustion and pyrolysis of biomass-derived fuels was compiled by assembling selected reaction subsets from existing mechanisms (parents). The mechanism, here referred to as ''AaA,'' includes reaction subsets for the oxidation of hydrogen (H{sub 2}), carbon monoxide (CO), light hydrocarbons (C{sub 1} and C{sub 2}), and methanol (CH{sub 3}OH). The mechanism also takes into account reaction subsets of nitrogen pollutants, including the reactions relevant to staged combustion, reburning, and selective noncatalytic reduction (SNCR). The AaA mechanism was validated against suitable experimental data from the literature. Overall, the AaA mechanism gavemore » more accurate predictions than three other mechanisms of reference, although the reference mechanisms performed better occasionally. The predictions from AaA were also found to be consistent with the predictions of its parent mechanisms within most of their range of validity, thus transferring the validity of the parents to the inheriting mechanism (AaA). In parametric studies the AaA mechanism predicted that the effect of methanol on combustion and pollutants is often similar to that of light hydrocarbons, but it also showed that there are important exceptions, thus suggesting that methanol should be taken into account when simulating biomass combustion. To our knowledge, the AaA mechanism is currently the only mechanism that accounts for the chemistry of methanol and nitrogen relevant to the gas-phase combustion and pyrolysis of biomass-derived fuels. (author)« less

Increased AAA-TOB3 correlates with lymph node metastasis and advanced stage of lung adenocarcinoma.

PubMed

Liu, Yanfeng; Bu, Lina; Li, Wei; Wu, Wei; Wang, Shengyu; Diao, Xin; Zhou, Jing; Chen, Guoan; Yang, Shuanying

2017-07-24

This study was to investigate the differential mitochondrial protein expressions in human lung adenocarcinoma and provide preliminary data for further exploration of the carcinogenic mechanism. Total proteins of A549 and 16HBE mitochondria were extracted through 2D polyacrylamide gel electrophoresis (2-DE). The differential mitochondria proteins were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and were further confirmed by Western blot, immunoelectron microscopy and immunohistochemistry (IHC) in A549 cells as well as lung adenocarcinoma tissues. A total of 41 differentially expressed protein spots were found in A549 mitochondria. Of them, 15 proteins were highly expressed and 26 proteins were lowly expressed in the mitochondria of A549 (by more than 1.5 times). Among the 15 more highly expressed proteins, AAA-TOB3 (by more than 3 times) was highly expressed in the mitochondria of A549 compared with the 16HBE, by LC-MS/MS identification. High electron density and clear circular colloidal gold-marked AAA-TOB3 particles were observed in the A549 cells via immunoelectron microscopy. Besides, AAA-TOB3 was confirmed to be elevated in lung adenocarcinoma by Western blot and IHC. Moreover, increased AAA-TOB3 correlated with lymph node metastasis and advanced stage of lung adenocarcinoma (p<0.05). AAA-TOB3 was highly expressed in lung adenocarcinoma, and the up-regulation of AAA-TOB3 correlated with lymph node metastasis and advanced stage of lung adenocarcinoma, which suggested that it could serve as a potential molecular marker for lung adenocarcinoma.

Second-order near-wall turbulence closures - A review

NASA Technical Reports Server (NTRS)

So, R. M. C.; Lai, Y. G.; Zhang, H. S.; Hwang, B. C.

1991-01-01

Advances in second-order near-wall turbulence closures are summarized. All closures under consideration are based on high-Reynolds-number models. Most near-wall closures proposed to date attempt to modify the high-Reynolds-number models for the dissipation function and the pressure redistribution term so that the resultant models are applicable all the way to the wall. The asymptotic behavior of the near-wall closures is examined and compared with the proper near-wall behavior of the exact Reynolds-stress equations. It is found that three second-order near-wall closures give the best correlations with simulated turbulence statistics. However, their predictions of near-wall Reynolds-stress budgets are considered to be incorrect. A proposed modification to the dissipitation-rate equation remedies part of those predictions. It is concluded that further improvements are required if a complete replication of all the turbulence properties and Reynolds-stress budgets by a statistical model of turbulence is desirable.

MitoCPR-A surveillance pathway that protects mitochondria in response to protein import stress.

PubMed

Weidberg, Hilla; Amon, Angelika

2018-04-13

Mitochondrial functions are essential for cell viability and rely on protein import into the organelle. Various disease and stress conditions can lead to mitochondrial import defects. We found that inhibition of mitochondrial import in budding yeast activated a surveillance mechanism, mitoCPR, that improved mitochondrial import and protected mitochondria during import stress. mitoCPR induced expression of Cis1, which associated with the mitochondrial translocase to reduce the accumulation of mitochondrial precursor proteins at the mitochondrial translocase. Clearance of precursor proteins depended on the Cis1-interacting AAA + adenosine triphosphatase Msp1 and the proteasome, suggesting that Cis1 facilitates degradation of unimported proteins. mitoCPR was required for maintaining mitochondrial functions when protein import was compromised, demonstrating the importance of mitoCPR in protecting the mitochondrial compartment. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Vascular surgical society of great britain and ireland: immunoglobulin A antibodies against chlamydia pneumoniae are associated with expansion of small abdominal aortic aneurysms and declining ankle blood pressure

PubMed

Lindholt; Vammen; Henneberg; Fasting

1999-05-01

BACKGROUND: The potential correlation between chronic infection with Chlamydia pneumoniae and the progression of small abdominal aortic aneurysms (AAAs) and lower limb atherosclerosis was studied. METHODS: Mass screening for AAA was carried out in outdoor clinics at all hospitals in the county. Some 139 men (aged 65-73 years) with a 3.0-4.9-cm AAA were followed prospectively for 1-3 (mean 2.7) years. Initially, an interview and examination was performed, and blood samples were taken. RESULTS: Some 62 per cent (53-71 per cent) had an immunoglobulin (Ig) A level of 40 or more, or an IgG level of 64 or above. Some 83 per cent (74-93 per cent) had an IgA level of 20 or more, or an IgG level of 32 or more. Men with an IgA level of 20 or more had 51 per cent greater AAA expansion and men with an IgA level of 40 or above had 24 per cent more expansion. An IgA level of 20 or more, or IgA of 40 or greater, were significant independent predictors of AAA expansion adjusted for age, smoking, initial AAA size, steroid treatment, diastolic blood pressure, pulmonary function and other plasma factors. The ankle blood pressure index (ABI) of the IgA-seropositive men decreased 11 per cent, while the ABI decreased by 5 per cent among IgA-seronegative men (P < 0.05). The significant difference persisted after adjusting for age, smoking, initial systolic ankle blood pressure, initial brachial systolic or diastolic blood pressure, but disappeared after adjusting for low-density lipoprotein (LDL) levels. CONCLUSION: A high proportion of men with a small AAA have signs of chronic C. pneumoniae infection. The progression of AAAs and lower limb atherosclerosis seems to be correlated to chronic infection with C. pneumoniae.

Identifying patients with AAA with the highest risk following endovascular repair.

PubMed

Cadili, Ali; Turnbull, Robert; Hervas-Malo, Marilou; Ghosh, Sunita; Chyczij, Harold

2012-08-01

It has been demonstrated that endovascular repair of arterial disease results in reduced perioperative morbidity and mortality compared to open surgical repair. The rates of complications and need for reinterventions, however, have been found to be higher than that in open repair. The purpose of this study was to identify the predictors of endograft complications and mortality in patients undergoing endovascular abdominal aortic aneurysm (AAA) repair; specifically, our aim was to identify a subset of patients with AAA whose risk of periprocedure mortality was so high that they should not be offered endovascular repair. We undertook a prospective review of patients with AAA receiving endovascular therapy at a single institution. Collected variables included age, gender, date of procedure, indication for procedure, size of aneurysm (where applicable), type of endograft used, presence of rupture, American Society of Anesthesiologists (ASA) class, major medical comorbidities, type of anesthesia (general, epidural, or local), length of intensive care unit (ICU) stay, and length of hospital stay. These factors were correlated with the study outcomes (overall mortality, graft complications, morbidity, and reintervention) using univariate and multivariate logistic regression. A total of 199 patients underwent endovascular AAA repair during the study period. The ICU stay, again, was significantly correlated with the primary outcomes (death and graft complications). In addition, length of hospital stay greater than 3 days, also emerged as a statistically significant predictor of graft complications in this subgroup (P = .024). Survival analysis for patients with AAA revealed that age over 85 years and ICU stay were predictive of decreased survival. Statistical analysis for other subgroups of patients (inflammatory AAA or dissection) was not performed due to the small numbers in these subgroups. Patients with AAA greater than 85 years of age are at a greater risk of mortality following endovascular repair. In addition, patients who are expected to require postprocedure ICU admission are also at an increased risk of mortality following endovascular repair.

Thermal-stress analysis of IFMIF target back-wall made of reduced-activation ferritic steel and austenitic stainless steel

NASA Astrophysics Data System (ADS)

Ida, Mizuho; Chida, Teruo; Furuya, Kazuyuki; Wakai, Eiichi; Nakamura, Hiroo; Sugimoto, Masayoshi

2009-04-01

For long time operation of a liquid lithium target of the International Fusion Materials Irradiation Facility, annual replacement of a back-wall, a part of the flow channel, is planned, since the target suffers neutron damage of more than 50 dpa/fpy. Considering irradiation/activation conditions, remote weld on stainless steel 316L between a back-wall and a target assembly was employed. Furthermore, dissimilar weld between the 316L and a reduced-activation ferritic/martensitic steel F82H in the back-wall was employed. The objective of this study is to clarify structures and materials of the back-wall with acceptable thermal-stress under nuclear heating. Thermal-stress analysis was done using a code ABAQUS and data of the nuclear heating. As a result, thermal-stress in the back-wall is acceptable level, if thickness of the stress-mitigation part is more than 5 mm. With results of the analysis, necessity of material data for F82H and 316L under conditions of irradiation tests and mechanical tests are clarified.

49 CFR 178.45 - Specification 3T seamless steel cylinder.

Code of Federal Regulations, 2011 CFR

2011-10-01

..., and service pressure. A DOT 3T cylinder is a seamless steel cylinder with a minimum water capacity of...) Wall thickness. The minimum wall thickness must be such that the wall stress at the minimum specified... the physical tests required in paragraphs (j) and (k) of this section. A wall stress of more than 90...

One-year outcomes after ruptured abdominal aortic aneurysms repair: is evar the best choice? A single-center experience.

PubMed

Martinelli, O; Fenelli, C; Ben-Hamida, J; Fresilli, M; Irace, F G; Picone, V; Malaj, A; Gossetti, B; Irace, L

2018-06-06

Treatment of ruptured abdominal aortic aneurysms (rAAAs) is still burdened by high morbidity and mortality. Although endovascular aortic repair (EVAR) offers encouraging results in elective setting, its role as first line strategy to treat rAAA is still debated. Our aim was to compare early and late outcomes in patients undergoing open surgical repair (OSR) compared with those submitted to vs EVAR for rAAAs. A retrospective review of data extracted from medical records identified 105 consecutive patients with rAAA who were submitted to open or endovascular repairs from 2008 to 2016. Primary endpoint was to assess the rAAA-related mortality in the immediate postoperative, within 1 month and 1 year after ORS and EVAR Secondary endpoints included: length of stay, AAA-related postoperative complications such as acute limb ischemia, myocardial infarction, renal and respiratory failure and rAAA-related re-interventions. Statistical analysis was performed using the Fisher exact test,χ2 test and logistic regression calculations. Early and midterm survival rates were assessed with Cox model. Of the 105 patients with rAAA 70.48% underwent OSR including 41.89% which was hemodynamically (Hd) unstable and the remaining 29.52% was submitted to rEVAR. (all Hd stable). Compared EVAR group, the OSR group had a higher RAAA-related mortality rate for both Hd stable and Hd unstable patients: 18.92% vs 6.45% at 24 hours; (P = .185) 39.19% vs 19.35% at 30 days (P = .082); 44.59% vs 38.71% at 1 year (P = .734) If only Hd stable patients were considered, mortality following OSR and EVAR was: 6.98% vs 6.45% at 24 hours (P = .703); 27.91% vs 19.35% at 30 days (P = .567); 32.56% vs 38.71% at 1 year (P = .764). Mean length of stay for patients was 15 days after OSR and 10 days after rEVAR (P = .002). At 1-year follow-up, the overall rAAA-related complications incidence was higher in the rEVAR group than in the OSR group (47.85% vs 18.33%; P = .008); re-interventions were 18.33% in OSR group vs 21.82% in EVAR group (P = .917). Cox model showed that instability and coronary artery disease were predictors of overall mortality of rAAAs. EVAR does not independently reduce 1-year mortality in comparison with OSR in Hd-stable patients. Urgent EVAR for rAAAs in unstable patients can be limited by logistical problems. It follows that patients selected for OSR have a more complex aortic anatomy and worse Hd status than those sumitted to rEVAR. rEVAR burdened by a higher incidence of procedure-related complications than OSR. Reconfiguration of acute aortic services and establishment of standardized institutional protocols might be advisable for improvements in the management of ruptured AAA. A carefully evaluation of whether the benefits of an endovascular strategy translate into longer term benefit is needed before definitive conclusions can be drawn about the advantages of EVAR as first-line strategy for ruptured aneurysms. Copyright © 2018 Elsevier Inc. All rights reserved.

On the role of stress anisotropy in the growth of stems.

PubMed

Baskin, Tobias I; Jensen, Oliver E

2013-11-01

We review the role of anisotropic stress in controlling the growth anisotropy of stems. Instead of stress, growth anisotropy is usually considered in terms of compliance. Anisotropic compliance is typical of cell walls, because they contain aligned cellulose microfibrils, and it appears to be sufficient to explain the growth anisotropy of an isolated cell. Nevertheless, a role for anisotropic stress in the growth of stems is indicated by certain growth responses that appear too rapid to be accounted for by changes in cell-wall compliance and because the outer epidermal wall of most growing stems has microfibrils aligned axially, an arrangement that would favour radial expansion based on cell-wall compliance alone. Efforts to quantify stress anisotropy in the stem have found that it is predominantly axial, and large enough in principle to explain the elongation of the epidermis, despite its axial microfibrils. That the epidermis experiences a stress deriving from the inner tissue, the so-called 'tissue stress', has been widely recognized; however, the origin of the dominant axial direction remains obscure. Based on geometry, an isolated cylindrical cell should have an intramural stress anisotropy favouring the transverse direction. Explanations for tissue stress have invoked differential elastic moduli, differential plastic deformation (so-called differential growth), and a phenomenon analogous to the maturation stress generated by secondary cell walls. None of these explanations has been validated. We suggest that understanding the role of stress anisotropy in plant growth requires a deeper understanding of the nature of stress in hierarchical, organic structures.

Seismic amplitude measurements suggest foreshocks have different focal mechanisms than aftershocks

USGS Publications Warehouse

Lindh, A.; Fuis, G.; Mantis, C.

1978-01-01

The ratio of the amplitudes of P and S waves from the foreshocks and aftershocks to three recent California earthquakes show a characteristic change at the time of the main events. As this ratio is extremely sensitive to small changes in the orientation of the fault plane, a small systematic change in stress or fault configuration in the source region may be inferred. These results suggest an approach to the recognition of foreshocks based on simple measurements of the amplitudes of seismic waves. Copyright ?? 1978 AAAS.

Previously Identified Deficiencies Not Corrected in the General Fund Enterprise Business System Program

DTIC Science & Technology

2011-06-15

Army AAA Report No. A-2009-0226- FFM , “Examination of Federal Financial Management Improvement Act Compliance - Test Validation General Fund Enterprise...Business System Release 1.2,” September 30, 2009 AAA Report No. A-2009-0231- FFM , “General Fund Enterprise Business System - Federal Financial...Management Improvement Act Compliance Examination of Release 1.3 Functionality,” September 30, 2009 AAA Report No. A-2009-0232- FFM , “General Fund

Genetic Variations in SLCO Transporter Genes Contributing to Racial Disparity in Aggressiveness of Prostate Cancer

DTIC Science & Technology

2016-10-01

Contract Specialist U.S. Army Medical Research Acquisition Activity, MCMR- AAA -E, 820 Chandler Street, Fort Detrick, MD 21702-5014 Phone: (301) 619-4018...Funding Agency’s Procuring Contracting/Grants Officer: Ayi Ayayi, Contract Specialist U.S. Army Medical Research Acquisition Activity, MCMR- AAA -E, 820...Ayayi, Contract Specialist, U.S. Army Medical Research Acquisition Activity, MCMR- AAA -E, 820 Chandler Street, Fort Detrick, MD 21702-5014 Phone

Updates on AAA screening and surveillance

PubMed

Theivendran, Mayo; Chuen, Jason

2018-05-01

Screening and diagnostic surveillance of latent conditions have a profound impact on public healthcare expenditure and clinical outcomes. Abdominal aortic aneurysm (AAA) remains one of the hallmark pathologies in vascular surgery and an area of intense research interest. This article is the second of two that will outline current areas of controversy and research in AAA disease in order to support a more detailed understanding of issues in managing patients with this condition, and inform the development of Australasian clinical guidelines and health policy. Screening and surveillance of AAA should be evidence-based and follow clinical guidelines; however, advances in treatment technology and epidemiological data have influenced results. Goals of care and cost‑effectiveness should play central parts in screening and surveillance strategies.

Ruptured abdominal aortic aneurysm: Is endovascular aneurysm repair the answer for everybody?

PubMed

Aziz, Faisal

2016-03-01

Treatment paradigms for elective repair of asymptomatic abdominal aortic aneurysms (AAA) have evolved during the past 2 decades, with endovascular aneurysm repair as the preferred treatment modality. The patient care strategy for emergent treatment for ruptured AAA is not as straightforward, due in part to surgeon expertise and stent-graft availability at the institution. Although most reports have extrapolated elective endovascular aneurysm repair feasibility data to the ruptured AAA patient and the aneurysm anatomy, these expectations should be interpreted with caution. In the absence of level I evidence, and lack of adequate local hospital resources, endovascular aneurysm repair-first policy might not be feasible for all the patients who present with ruptured AAA. Copyright © 2016 Elsevier Inc. All rights reserved.

Novel Molecular Imaging Approaches to Abdominal Aortic Aneurysm Risk Stratification

PubMed Central

Toczek, Jakub; Meadows, Judith L.; Sadeghi, Mehran M.

2015-01-01

Selection of patients for abdominal aortic aneurysm (AAA) repair is currently based on aneurysm size, growth rate and symptoms. Molecular imaging of biological processes associated with aneurysm growth and rupture, e.g., inflammation and matrix remodeling, could improve patient risk stratification and lead to a reduction in AAA morbidity and mortality. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and ultrasmall superparamagnetic particles of iron oxide (USPIO) magnetic resonance imaging are two novel approaches to AAA imaging evaluated in clinical trials. A variety of other tracers, including those that target inflammatory cells and proteolytic enzymes (e.g., integrin αvβ3 and matrix metalloproteinases), have proven effective in preclinical models of AAA and show great potential for clinical translation. PMID:26763279

The AAA protein spastin possesses two levels of basal ATPase activity.

PubMed

Fan, Xiangyu; Lin, Zhijie; Fan, Guanghui; Lu, Jing; Hou, Yongfei; Habai, Gulijiazi; Sun, Linyue; Yu, Pengpeng; Shen, Yuequan; Wen, Maorong; Wang, Chunguang

2018-05-01

The AAA ATPase spastin is a microtubule-severing enzyme that plays important roles in various cellular events including axon regeneration. Herein, we found that the basal ATPase activity of spastin is negatively regulated by spastin concentration. By determining a spastin crystal structure, we demonstrate the necessity of intersubunit interactions between spastin AAA domains. Neutralization of the positive charges in the microtubule-binding domain (MTBD) of spastin dramatically decreases the ATPase activity at low concentration, although the ATP-hydrolyzing potential is not affected. These results demonstrate that, in addition to the AAA domain, the MTBD region of spastin is also involved in regulating ATPase activity, making interactions between spastin protomers more complicated than expected. © 2018 Federation of European Biochemical Societies.

Role of AAA(+)-proteins in peroxisome biogenesis and function.

PubMed

Grimm, Immanuel; Erdmann, Ralf; Girzalsky, Wolfgang

2016-05-01

Mutations in the PEX1 gene, which encodes a protein required for peroxisome biogenesis, are the most common cause of the Zellweger spectrum diseases. The recognition that Pex1p shares a conserved ATP-binding domain with p97 and NSF led to the discovery of the extended family of AAA+-type ATPases. So far, four AAA+-type ATPases are related to peroxisome function. Pex6p functions together with Pex1p in peroxisome biogenesis, ATAD1/Msp1p plays a role in membrane protein targeting and a member of the Lon-family of proteases is associated with peroxisomal quality control. This review summarizes the current knowledge on the AAA+-proteins involved in peroxisome biogenesis and function.

Dehydration induced loss of photosynthesis in Arabidopsis leaves during senescence is accompanied by the reversible enhancement in the activity of cell wall β-glucosidase.

PubMed

Patro, Lichita; Mohapatra, Pranab Kishor; Biswal, Udaya Chand; Biswal, Basanti

2014-08-01

The physiology of loss of photosynthetic production of sugar and the consequent cellular sugar reprogramming during senescence of leaves experiencing environmental stress largely remains unclear. We have shown that leaf senescence in Arabidopsis thaliana causes a significant reduction in the rate of oxygen evolution and net photosynthetic rate (Pn). The decline in photosynthesis is further aggravated by dehydration. During dehydration, primary photochemical reaction of thylakoids and net photosynthesis decrease in parallel with the increase in water deficit. Senescence induced loss in photosynthesis is accompanied by a significant increase in the activity of cell wall hydrolyzing enzyme such as β-glucosidase associated with cell wall catabolism. The activity of this enzyme is further enhanced when the senescing leaves experience dehydration stress. It is possible that both senescence and stress separately or in combination result in the loss in photosynthesis which could be a signal for an enhancement in the activity of β-glucosidase that breaks down cell wall polysaccharides to sugar to sustain respiration for metabolic activities of plants experiencing stress. Thus dehydration response of cell wall hydrolases of senescing leaves is considered as plants' strategy to have cell wall polysaccharides as an alternative energy source for completion of energy requiring senescence process, stress survival and maintenance of recovery potential of energy deficit cells in the background of loss in photosynthesis. Withdrawal of stress (rehydration) distinctly exhibits recovery of photosynthesis and suppression of enzyme activity. Retention of the signaling for sugar reprogramming through breakdown of cell wall polysaccharides in the senescing leaves exposed to severe drought stress suggests that senescing leaves like mature ones possess potential for stress recovery. The precise mechanism of stress adaptation of senescing leaves is yet to be known. A significant accumulation of anthocyanin and flavonoids may be an indicator of stress adaptation of senescing leaves. In addition, stress induced enhancement of nonphotochemical quenching (NPQ), a stress protection provision in green plants, also suggests the potential of the leaves to develop adaptational mechanism to counter the dehydration stress. Copyright © 2014 Elsevier B.V. All rights reserved.

Correlation between vortices and wall shear stress in a curved artery model under pulsatile flow conditions

NASA Astrophysics Data System (ADS)

Cox, Christopher; Plesniak, Michael W.

2017-11-01

One of the most physiologically relevant factors within the cardiovascular system is the wall shear stress. The wall shear stress affects endothelial cells via mechanotransduction and atherosclerotic regions are strongly correlated with curvature and branching in the human vasculature, where the shear stress is both oscillatory and multidirectional. Also, the combined effect of curvature and pulsatility in cardiovascular flows produces unsteady vortices. In this work, our goal is to assess the correlation between multiple vortex pairs and wall shear stress. To accomplish this, we use an in-house high-order flux reconstruction Navier-Stokes solver to simulate pulsatile flow of a Newtonian blood-analog fluid through a rigid 180° curved artery model. We use a physiologically relevant flow rate and generate results using both fully developed and uniform entrance conditions, the latter motivated by the fact that flow upstream to a curved artery may not be fully developed. Under these two inflow conditions, we characterize the evolution of various vortex pairs and their subsequent effect on several wall shear stress metrics. Supported by GW Center for Biomimetics and Bioinspired Engineering.

Runge-Kutta method for wall shear stress of blood flow in stenosed artery

NASA Astrophysics Data System (ADS)

Awaludin, Izyan Syazana; Ahmad, Rokiah@Rozita

2014-06-01

A mathematical model of blood flow through stenotic artery is considered. A stenosis is defined as the partial occlusion of the blood vessels due to the accumulation of cholesterols, fats and the abnormal growth of tissue on the artery walls. The development of stenosis in the artery is one of the factors that cause problem in blood circulation system. This study was conducted to determine the wall shear stress of blood flow in stenosed artery. Modified mathematical model is used to analyze the relationship of the wall shear stress versus the length and height of stenosis. The existing models that have been created by previous researchers are solved using fourth order Runge-Kutta method. Numerical results show that the wall shear stress is proportionate to the length and height of stenosis.

Cell wall pectic arabinans influence the mechanical properties of Arabidopsis thaliana inflorescence stems and their response to mechanical stress.

PubMed

Verhertbruggen, Yves; Marcus, Susan E; Chen, Jianshe; Knox, J Paul

2013-08-01

Little is known of the dynamics of plant cell wall matrix polysaccharides in response to the impact of mechanical stress on plant organs. The capacity of the imposition of a mechanical stress (periodic brushing) to reduce the height of the inflorescence stem of Arabidopsis thaliana seedlings has been used to study the role of pectic arabinans in the mechanical properties and stress responsiveness of a plant organ. The arabinan-deficient-1 (arad1) mutation that affects arabinan structures in epidermal cell walls of inflorescence stems is demonstrated to reduce the impact on inflorescence stem heights caused by mechanical stress. The arabinan-deficient-2 (arad2) mutation, that does not have detectable impact on arabinan structures, is also shown to reduce the impact on stem heights caused by mechanical stress. The LM13 linear arabinan epitope is specifically detected in epidermal cell walls of the younger, flexible regions of inflorescence stems and increases in abundance at the base of inflorescence stems in response to an imposed mechanical stress. The strain (percentage deformation) of stem epidermal cells in the double mutant arad1 × arad2 is lower in unbrushed plants than in wild-type plants, but rises to wild-type levels in response to brushing. The study demonstrates the complexity of arabinan structures within plant cell walls and also that their contribution to cell wall mechanical properties is a factor influencing responsiveness to mechanical stress.

Quantification of wall shear stress in large blood vessels using Lagrangian interpolation functions with cine phase-contrast magnetic resonance imaging.

PubMed

Cheng, Christopher P; Parker, David; Taylor, Charles A

2002-09-01

Arterial wall shear stress is hypothesized to be an important factor in the localization of atherosclerosis. Current methods to compute wall shear stress from magnetic resonance imaging (MRI) data do not account for flow profiles characteristic of pulsatile flow in noncircular vessel lumens. We describe a method to quantify wall shear stress in large blood vessels by differentiating velocity interpolation functions defined using cine phase-contrast MRI data on a band of elements in the neighborhood of the vessel wall. Validation was performed with software phantoms and an in vitro flow phantom. At an image resolution corresponding to in vivo imaging data of the human abdominal aorta, time-averaged, spatially averaged wall shear stress for steady and pulsatile flow were determined to be within 16% and 23% of the analytic solution, respectively. These errors were reduced to 5% and 8% with doubling in image resolution. For the pulsatile software phantom, the oscillation in shear stress was predicted to within 5%. The mean absolute error of circumferentially resolved shear stress for the nonaxisymmetric phantom decreased from 28% to 15% with a doubling in image resolution. The irregularly shaped phantom and in vitro investigation demonstrated convergence of the calculated values with increased image resolution. We quantified the shear stress at the supraceliac and infrarenal regions of a human abdominal aorta to be 3.4 and 2.3 dyn/cm2, respectively.

Debonding Stress Concentrations in a Pressurized Lobed Sandwich-Walled Generic Cryogenic Tank

NASA Technical Reports Server (NTRS)

Ko, William L.

2004-01-01

A finite-element stress analysis has been conducted on a lobed composite sandwich tank subjected to internal pressure and cryogenic cooling. The lobed geometry consists of two obtuse circular walls joined together with a common flat wall. Under internal pressure and cryogenic cooling, this type of lobed tank wall will experience open-mode (a process in which the honeycomb is stretched in the depth direction) and shear stress concentrations at the junctures where curved wall changes into flat wall (known as a curve-flat juncture). Open-mode and shear stress concentrations occur in the honeycomb core at the curve-flat junctures and could cause debonding failure. The levels of contributions from internal pressure and temperature loading to the open-mode and shear debonding failure are compared. The lobed fuel tank with honeycomb sandwich walls has been found to be a structurally unsound geometry because of very low debonding failure strengths. The debonding failure problem could be eliminated if the honeycomb core at the curve-flat juncture is replaced with a solid core.

Dimensionless number is central to stress relaxation and expansive growth of the cell wall.

PubMed

Ortega, Joseph K E

2017-06-07

Experiments demonstrate that both plastic and elastic deformation of the cell wall are necessary for wall stress relaxation and expansive growth of walled cells. A biophysical equation (Augmented Growth Equation) was previously shown to accurately model the experimentally observed wall stress relaxation and expansive growth rate. Here, dimensional analysis is used to obtain a dimensionless Augmented Growth Equation with dimensionless coefficients (groups of variables, or Π parameters). It is shown that a single Π parameter controls the wall stress relaxation rate. The Π parameter represents the ratio of plastic and elastic deformation rates, and provides an explicit relationship between expansive growth rate and the wall's mechanical properties. Values for Π are calculated for plant, algal, and fungal cells from previously reported experimental results. It is found that the Π values for each cell species are large and very different from each other. Expansive growth rates are calculated using the calculated Π values and are compared to those measured for plant and fungal cells during different growth conditions, after treatment with IAA, and in different developmental stages. The comparison shows good agreement and supports the claim that the Π parameter is central to expansive growth rate of walled cells.

Dosimetric comparison of Acuros XB deterministic radiation transport method with Monte Carlo and model-based convolution methods in heterogeneous media

PubMed Central

Han, Tao; Mikell, Justin K.; Salehpour, Mohammad; Mourtada, Firas

2011-01-01

Purpose: The deterministic Acuros XB (AXB) algorithm was recently implemented in the Eclipse treatment planning system. The goal of this study was to compare AXB performance to Monte Carlo (MC) and two standard clinical convolution methods: the anisotropic analytical algorithm (AAA) and the collapsed-cone convolution (CCC) method. Methods: Homogeneous water and multilayer slab virtual phantoms were used for this study. The multilayer slab phantom had three different materials, representing soft tissue, bone, and lung. Depth dose and lateral dose profiles from AXB v10 in Eclipse were compared to AAA v10 in Eclipse, CCC in Pinnacle3, and EGSnrc MC simulations for 6 and 18 MV photon beams with open fields for both phantoms. In order to further reveal the dosimetric differences between AXB and AAA or CCC, three-dimensional (3D) gamma index analyses were conducted in slab regions and subregions defined by AAPM Task Group 53. Results: The AXB calculations were found to be closer to MC than both AAA and CCC for all the investigated plans, especially in bone and lung regions. The average differences of depth dose profiles between MC and AXB, AAA, or CCC was within 1.1, 4.4, and 2.2%, respectively, for all fields and energies. More specifically, those differences in bone region were up to 1.1, 6.4, and 1.6%; in lung region were up to 0.9, 11.6, and 4.5% for AXB, AAA, and CCC, respectively. AXB was also found to have better dose predictions than AAA and CCC at the tissue interfaces where backscatter occurs. 3D gamma index analyses (percent of dose voxels passing a 2%∕2 mm criterion) showed that the dose differences between AAA and AXB are significant (under 60% passed) in the bone region for all field sizes of 6 MV and in the lung region for most of field sizes of both energies. The difference between AXB and CCC was generally small (over 90% passed) except in the lung region for 18 MV 10 × 10 cm2 fields (over 26% passed) and in the bone region for 5 × 5 and 10 × 10 cm2 fields (over 64% passed). With the criterion relaxed to 5%∕2 mm, the pass rates were over 90% for both AAA and CCC relative to AXB for all energies and fields, with the exception of AAA 18 MV 2.5 × 2.5 cm2 field, which still did not pass. Conclusions: In heterogeneous media, AXB dose prediction ability appears to be comparable to MC and superior to current clinical convolution methods. The dose differences between AXB and AAA or CCC are mainly in the bone, lung, and interface regions. The spatial distributions of these differences depend on the field sizes and energies. PMID:21776802

Comparison of cell-type-specific vs transmural aortic gene expression in experimental aneurysms.

PubMed

Sho, Eiketsu; Sho, Mien; Nanjo, Hiroshi; Kawamura, Koichi; Masuda, Hirotake; Dalman, Ronald L

2005-05-01

Abdominal aortic aneurysm (AAA) progression and disease resistance are related to mural cellularity; adventitial macrophages and neocapillaries predominate in larger, advanced aneurysms, whereas smaller AAAs have fewer macrophages and retain more medial smooth muscle cells (SMCs). Expression analysis of mRNA derived from the entire aorta may mask the role that specific cell types play in modulating disease progression. We used laser capture microdissection (LCM) to isolate SMC and macrophage-predominant mural cell populations for gene expression analysis in variable-flow AAA. Rat AAAs were created via porcine pancreatic elastase (PPE) infusion. Aortic flow was increased via femoral arteriovenous fistula creation (HF-AAA) or reduced via unilateral iliac ligation (LF-AAA) in selected cohorts. SMC and macrophage-predominant cell populations were isolated via LCM and analyzed for expression of pro-inflammatory transcription factors and chemokines, cytokines, and proteolytic enzymes via real-time polymerase chain reaction. Aortic PPE infusion precipitated endothelial cell (EC) denudation, SMC apoptosis, and elastic lamellar degeneration. Increased aortic flow (HF > NF > LF) stimulated restorative EC and SMC proliferation (45.8 +/- 6.6 > 30.5 +/- 2.1 > 21 +/- 3.6 and 212.2 +/- 9.8 > 136.5 +/- 8.9 > 110 +/- 13.5, respectively, for both cell types; P < .05) at 5 days after PPE infusion, while simultaneously reducing medial SMC apoptosis and transmural macrophage infiltration. Expression of nuclear factor kappa B (NF-kappab), granulocyte macrophage-colony stimulating factor (GM-CSF), macrophage migration inhibitory (MIF), heparin-binding EGF-like factor (HB-EGF) and inducible nitric oxide synthase (iNOS) varied between cell types and flow conditions at all time points examined. Gelatinolytic protease expression varied by cell type in response to flow loading (eg, increased in SMCs, decreased in macrophages), consistent with observed patterns of elastolysis and SMC proliferation reported in prior experiments. Flow differentially regulates cell-specific AAA gene expression. Whole-organ analysis of AAA tissue lysates obscures important cellular responses to inflammation and flow, and may explain previous seemingly contradictory observations regarding proteolysis and cell proliferation. Cell-type specific expression and functional analyses may substantially clarify the pathophysiology of AAA disease. Understanding aneurysmal aortic degeneration at the most fundamental level is a critical precursor to the development of next-generation therapies such as drug-eluting endografts and/or medical therapies to limit expansion of preclinical AAA in high-risk or elderly patients. Although animal modeling is necessary to gain insight into the early initiating events of AAA disease, the methods used in such analyses have critical bearing on the conclusions drawn regarding pathogenesis and potential therapeutic derivations. By analyzing cell-type-specific gene expression rather than whole-organ tissue lysates, the precise roles of important mediators such as metalloproteinases can be placed in the appropriate context. Further refinement of these techniques may allow cell-specific therapies to be applied at defined time points in disease progression with improved patient outcome and reduced procedural morbidity.

Mating-Induced Shedding of Cell Walls, Removal of Walls from Vegetative Cells, and Osmotic Stress Induce Presumed Cell Wall Genes in Chlamydomonas1

PubMed Central

Hoffmann, Xenia-Katharina; Beck, Christoph F.

2005-01-01

The first step in sexual differentiation of the unicellular green alga Chlamydomonas reinhardtii is the formation of gametes. Three genes, GAS28, GAS30, and GAS31, encoding Hyp-rich glycoproteins that presumably are cell wall constituents, are expressed in the late phase of gametogenesis. These genes, in addition, are activated by zygote formation and cell wall removal and by the application of osmotic stress. The induction by zygote formation could be traced to cell wall shedding prior to gamete fusion since it was seen in mutants defective in cell fusion. However, it was absent in mutants defective in the initial steps of mating, i.e. in flagellar agglutination and in accumulation of adenosine 3′,5′-cyclic monophosphate in response to this agglutination. Induction of the three GAS genes was also observed when cultures were exposed to hypoosmotic or hyperosmotic stress. To address the question whether the induction seen upon cell wall removal from both gametes and vegetative cells was elicited by osmotic stress, cell wall removal was performed under isosmotic conditions. Also under such conditions an activation of the genes was observed, suggesting that the signaling pathway(s) is (are) activated by wall removal itself. PMID:16183845

Effect of food intake on left ventricular wall stress.

PubMed

Gårdinger, Ylva; Hlebowicz, Joanna; Björgell, Ola; Dencker, Magnus

2014-01-28

Left ventricular wall stress has been investigated in a variety of populations, but the effect of food intake has not been evaluated. We assessed whether left ventricular wall stress is affected by food intake in healthy subjects. Twenty-three healthy subjects aged 25.6 ± 4.5 years were investigated. Meridional end-systolic wall stress (ESS) and circumferential end-systolic wall stress (cESS) were measured before, 30 minutes after, and 110 minutes after a standardised meal. Both ESS and cESS decreased significantly (P < 0.001) from fasting values 30 minutes after the meal, and had not returned to baseline after 110 minutes. ESS decreased from 65 ± 16 kdynes/cm2 (fasting) to 44 ± 12 kdynes/cm2 30 minutes after, and to 58 ± 13 kdynes/cm2 110 minutes after eating. cESS decreased from 98 ± 24 kdynes/cm2 to 67 ± 18 kdynes/cm2 30 minutes after, and to 87 ± 19 kdynes/cm2 110 minutes after the meal. This study shows that left ventricular wall stress is affected by food intake in healthy subjects.

A film-based wall shear stress sensor for wall-bounded turbulent flows

NASA Astrophysics Data System (ADS)

Amili, Omid; Soria, Julio

2011-07-01

In wall-bounded turbulent flows, determination of wall shear stress is an important task. The main objective of the present work is to develop a sensor which is capable of measuring surface shear stress over an extended region applicable to wall-bounded turbulent flows. This sensor, as a direct method for measuring wall shear stress, consists of mounting a thin flexible film on the solid surface. The sensor is made of a homogeneous, isotropic, and incompressible material. The geometry and mechanical properties of the film are measured, and particles with the nominal size of 11 μm in diameter are embedded on the film's surface to act as markers. An optical technique is used to measure the film deformation caused by the flow. The film has typically deflection of less than 2% of the material thickness under maximum loading. The sensor sensitivity can be adjusted by changing the thickness of the layer or the shear modulus of the film's material. The paper reports the sensor fabrication, static and dynamic calibration procedure, and its application to a fully developed turbulent channel flow at Reynolds numbers in the range of 90,000-130,000 based on the bulk velocity and channel full height. The results are compared to alternative wall shear stress measurement methods.

SU-E-T-381: Evaluation of Calculated Dose Accuracy for Organs-At-Risk Located at Out-Of-Field in a Commercial Treatment Planning System for High Energy Photon Beams Produced From TrueBeam Accelerators

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, L; Ding, G

Purpose: Dose calculation accuracy for the out-of-field dose is important for predicting the dose to the organs-at-risk when they are located outside primary beams. The investigations on evaluating the calculation accuracy of treatment planning systems (TPS) on out-of-field dose in existing publications have focused on low energy (6MV) photon. This study evaluates out-of-field dose calculation accuracy of AAA algorithm for 15MV high energy photon beams. Methods: We used the EGSnrc Monte Carlo (MC) codes to evaluate the AAA algorithm in Varian Eclipse TPS (v.11). The incident beams start with validated Varian phase-space sources for a TrueBeam linac equipped with Millenniummore » 120 MLC. Dose comparisons between using AAA and MC for CT based realistic patient treatment plans using VMAT techniques for prostate and lung were performed and uncertainties of organ dose predicted by AAA at out-of-field location were evaluated. Results: The results show that AAA calculations under-estimate doses at the dose level of 1% (or less) of prescribed dose for CT based patient treatment plans using VMAT techniques. In regions where dose is only 1% of prescribed dose, although AAA under-estimates the out-of-field dose by 30% relative to the local dose, it is only about 0.3% of prescribed dose. For example, the uncertainties of calculated organ dose to liver or kidney that is located out-of-field is <0.3% of prescribed dose. Conclusion: For 15MV high energy photon beams, very good agreements (<1%) in calculating dose distributions were obtained between AAA and MC. The uncertainty of out-of-field dose calculations predicted by the AAA algorithm for realistic patient VMAT plans is <0.3% of prescribed dose in regions where the dose relative to the prescribed dose is <1%, although the uncertainties can be much larger relative to local doses. For organs-at-risk located at out-of-field, the error of dose predicted by Eclipse using AAA is negligible. This work was conducted in part using the resources of Varian research grant VUMC40590-R.« less

Crystal Structure and Biochemical Characterization of a Mycobacterium smegmatis AAA-Type Nucleoside Triphosphatase Phosphohydrolase (Msm0858).

PubMed

Unciuleac, Mihaela-Carmen; Smith, Paul C; Shuman, Stewart

2016-05-15

AAA proteins (ATPases associated with various cellular activities) use the energy of ATP hydrolysis to drive conformational changes in diverse macromolecular targets. Here, we report the biochemical characterization and 2.5-Å crystal structure of a Mycobacterium smegmatis AAA protein Msm0858, the ortholog of Mycobacterium tuberculosis Rv0435c. Msm0858 is a magnesium-dependent ATPase and is active with all nucleoside triphosphates (NTPs) and deoxynucleoside triphosphates (dNTPs) as substrates. The Msm0858 structure comprises (i) an N-terminal domain (amino acids [aa] 17 to 201) composed of two β-barrel modules and (ii) two AAA domains, D1 (aa 212 to 473) and D2 (aa 476 to 744), each of which has ADP in the active site. Msm0858-ADP is a monomer in solution and in crystallized form. Msm0858 domains are structurally homologous to the corresponding modules of mammalian p97. However, the position of the N-domain modules relative to the AAA domains in the Msm0858-ADP tertiary structure is different and would impede the formation of a p97-like hexameric quaternary structure. Mutational analysis of the A-box and B-box motifs indicated that the D1 and D2 AAA domains are both capable of ATP hydrolysis. Simultaneous mutations of the D1 and D2 active-site motifs were required to abolish ATPase activity. ATPase activity was effaced by mutation of the putative D2 arginine finger, suggesting that Msm0858 might oligomerize during the ATPase reaction cycle. A truncated variant Msm0858 (aa 212 to 745) that lacks the N domain was characterized as a catalytically active homodimer. Recent studies have underscored the importance of AAA proteins (ATPases associated with various cellular activities) in the physiology of mycobacteria. This study reports the ATPase activity and crystal structure of a previously uncharacterized mycobacterial AAA protein, Msm0858. Msm0858 consists of an N-terminal β-barrel domain and two AAA domains, each with ADP bound in the active site. Msm0858 is a structural homolog of mammalian p97, with respect to the linear order and tertiary structures of their domains. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

SU-E-T-516: Dosimetric Validation of AcurosXB Algorithm in Comparison with AAA & CCC Algorithms for VMAT Technique.

PubMed

Kathirvel, M; Subramanian, V Sai; Arun, G; Thirumalaiswamy, S; Ramalingam, K; Kumar, S Ashok; Jagadeesh, K

2012-06-01

To dosimetrically validate AcurosXB algorithm for Volumetric Modulated Arc Therapy (VMAT) in comparison with standard clinical Anisotropic Analytic Algorithm(AAA) and Collapsed Cone Convolution(CCC) dose calculation algorithms. AcurosXB dose calculation algorithm is available with Varian Eclipse treatment planning system (V10). It uses grid-based Boltzmann equation solver to predict dose precisely in lesser time. This study was made to realize algorithms ability to predict dose accurately as its delivery for which five clinical cases each of Brain, Head&Neck, Thoracic, Pelvic and SBRT were taken. Verification plans were created on multicube phantom with iMatrixx-2D detector array and then dose prediction was done with AcurosXB, AAA & CCC (COMPASS System) algorithm and the same were delivered onto CLINAC-iX treatment machine. Delivered dose was captured in iMatrixx plane for all 25 plans. Measured dose was taken as reference to quantify the agreement between AcurosXB calculation algorithm against previously validated AAA and CCC algorithm. Gamma evaluation was performed with clinical criteria distance-to-agreement 3&2mm and dose difference 3&2% in omnipro-I'MRT software. Plans were evaluated in terms of correlation coefficient, quantitative area gamma and average gamma. Study shows good agreement between mean correlation 0.9979±0.0012, 0.9984±0.0009 & 0.9979±0.0011 for AAA, CCC & Acuros respectively. Mean area gamma for criteria 3mm/3% was found to be 98.80±1.04, 98.14±2.31, 98.08±2.01 and 2mm/2% was found to be 93.94±3.83, 87.17±10.54 & 92.36±5.46 for AAA, CCC & Acuros respectively. Mean average gamma for 3mm/3% was 0.26±0.07, 0.42±0.08, 0.28±0.09 and 2mm/2% was found to be 0.39±0.10, 0.64±0.11, 0.42±0.13 for AAA, CCC & Acuros respectively. This study demonstrated that the AcurosXB algorithm had a good agreement with the AAA & CCC in terms of dose prediction. In conclusion AcurosXB algorithm provides a valid, accurate and speedy alternative to AAA and CCC algorithms in a busy clinical environment. © 2012 American Association of Physicists in Medicine.

Alfalfa Cellulose Synthase Gene Expression under Abiotic Stress: A Hitchhiker’s Guide to RT-qPCR Normalization

PubMed Central

Guerriero, Gea; Legay, Sylvain; Hausman, Jean-Francois

2014-01-01

Abiotic stress represents a serious threat affecting both plant fitness and productivity. One of the promptest responses that plants trigger following abiotic stress is the differential expression of key genes, which enable to face the adverse conditions. It is accepted and shown that the cell wall senses and broadcasts the stress signal to the interior of the cell, by triggering a cascade of reactions leading to resistance. Therefore the study of wall-related genes is particularly relevant to understand the metabolic remodeling triggered by plants in response to exogenous stresses. Despite the agricultural and economical relevance of alfalfa (Medicago sativa L.), no study, to our knowledge, has addressed specifically the wall-related gene expression changes in response to exogenous stresses in this important crop, by monitoring the dynamics of wall biosynthetic gene expression. We here identify and analyze the expression profiles of nine cellulose synthases, together with other wall-related genes, in stems of alfalfa plants subjected to different abiotic stresses (cold, heat, salt stress) at various time points (e.g. 0, 24, 72 and 96 h). We identify 2 main responses for specific groups of genes, i.e. a salt/heat-induced and a cold/heat-repressed group of genes. Prior to this analysis we identified appropriate reference genes for expression analyses in alfalfa, by evaluating the stability of 10 candidates across different tissues (namely leaves, stems, roots), under the different abiotic stresses and time points chosen. The results obtained confirm an active role played by the cell wall in response to exogenous stimuli and constitute a step forward in delineating the complex pathways regulating the response of plants to abiotic stresses. PMID:25084115

Arg753gln and Arg677 Trp Polymorphisms of Toll-Like Receptor 2 In Acute Apical Abscess

PubMed Central

Miri-Moghaddam, Ebrahim; Farhad Mollashahi, Narges; Naghibi, Nava; Garme, Yasaman; Bazi, Ali

2018-01-01

Statement of the Problem: Genetic polymorphisms can alter immunity response against pathogens, which in turn influence individuals’ susceptibility to certain infections. Purpose: Our aim was to determine the association of Arg753Gln (rs5743708) and Arg677Trp (rs12191786) polymorphisms of toll like receptor-2 gene with the two clinical forms of apical periodontitis: acute apical abscess (AAA) and asymptomatic apical periodontitis (AAP). Materials and Method: There were 50 patients with AAA as case group and 50 with AAP as control group. Genotyping was done using Tetra-ARMS (amplification refractory mutation system) PCR. Results: Heterozygous genotype of Arg677Trp polymorphism was associated with risk of AAA (OR=1.9, 95% CI: 0.7-5.5, p= 0.05). Although statistically insignificant, Arg677Trp polymorphism promoted the risk of AAA in dominant model (OR=2.1, 95% CI: 0.7-5.9, p> 0.05). The frequency of mutant allele (T) of Arg677Trp polymorphism was higher in AAA (14%) than AAP (7%) subjects (OR=1.7, 95% CI: 0.6-4.7). For Arg753Gln polymorphism, wild homozygous (GG) represented the dominant genotype in both cases (96%) and controls (100%). Variant allele (A) of Arg753Gln polymorphism was identified in 2% of AAA, while no individual represented with this allele in AAP subjects. Individuals with Arg753Gln; Arg677Trp (GG; TC) combination showed an elevated risk of AAA (OR=1.6, 95% CI: 0.5- 4.2, p> 0.05). Conclusion: Arg677Trp polymorphism of TLR-2 rendered a higher risk for the development of abscesses in apical periodontitis. It is recommended to explore role of this polymorphism in other populations. PMID:29854884

B-Cell Depletion Promotes Aortic Infiltration of Immunosuppressive Cells and Is Protective of Experimental Aortic Aneurysm.

PubMed

Schaheen, Basil; Downs, Emily A; Serbulea, Vlad; Almenara, Camila C P; Spinosa, Michael; Su, Gang; Zhao, Yunge; Srikakulapu, Prasad; Butts, Cherié; McNamara, Coleen A; Leitinger, Norbert; Upchurch, Gilbert R; Meher, Akshaya K; Ailawadi, Gorav

2016-11-01

B-cell depletion therapy is widely used for treatment of cancers and autoimmune diseases. B cells are abundant in abdominal aortic aneurysms (AAA); however, it is unknown whether B-cell depletion therapy affects AAA growth. Using experimental models of murine AAA, we aim to examine the effect of B-cell depletion on AAA formation. Wild-type or apolipoprotein E-knockout mice were treated with mouse monoclonal anti-CD20 or control antibodies and subjected to an elastase perfusion or angiotensin II infusion model to induce AAA, respectively. Anti-CD20 antibody treatment significantly depleted B1 and B2 cells, and strikingly suppressed AAA growth in both models. B-cell depletion resulted in lower circulating IgM levels, but did not affect the levels of IgG or cytokine/chemokine levels. Although the total number of leukocyte remained unchanged in elastase-perfused aortas after anti-CD20 antibody treatment, the number of B-cell subtypes was significantly lower. Interestingly, plasmacytoid dendritic cells expressing the immunomodulatory enzyme indole 2,3-dioxygenase were detected in the aortas of B-cell-depleted mice. In accordance with an increase in indole 2,3-dioxygenase+ plasmacytoid dendritic cells, the number of regulatory T cells was higher, whereas the expression of proinflammatory genes was lower in aortas of B-cell-depleted mice. In a coculture model, the presence of B cells significantly lowered the number of indole 2,3-dioxygenase+ plasmacytoid dendritic cells without affecting total plasmacytoid dendritic cell number. The present results demonstrate that B-cell depletion protects mice from experimental AAA formation and promotes emergence of an immunosuppressive environment in aorta. © 2016 American Heart Association, Inc.

Clonal Expansion of T Cells in Abdominal Aortic Aneurysm: A Role for Doxycycline as Drug of Choice?

PubMed Central

Kroon, Albert M.; Taanman, Jan-Willem

2015-01-01

Most reported studies with animal models of abdominal aortic aneurysm (AAA) and several studies with patients have suggested that doxycycline favourably modifies AAA; however, a recent large long-term clinical trial found that doxycycline did not limit aneurysm growth. Thus, there is currently no convincing evidence that doxycycline reduces AAA expansion. Here, we critically review the available experimental and clinical information about the effects of doxycycline when used as a pharmacological treatment for AAA. The view that AAA can be considered an autoimmune disease and the observation that AAA tissue shows clonal expansion of T cells is placed in the light of the well-known inhibition of mitochondrial protein synthesis by doxycycline. In T cell leukaemia animal models, this inhibitory effect of the antibiotic has been shown to impede T cell proliferation, resulting in complete tumour eradication. We suggest that the available evidence of doxycycline action on AAA is erroneously ascribed to its inhibition of matrix metalloproteinases (MMPs) by competitive binding of the zinc ion co-factor. Although competitive binding may explain the inhibition of proteolytic activity, it does not explain the observed decreases of MMP mRNA levels. We propose that the observed effects of doxycycline are secondary to inhibition of mitochondrial protein synthesis. Provided that serum doxycycline levels are kept at adequate levels, the inhibition will result in a proliferation arrest, especially of clonally expanding T cells. This, in turn, leads to the decrease of proinflammatory cytokines that are normally generated by these cells. The drastic change in cell type composition may explain the changes in MMP mRNA and protein levels in the tissue samples. PMID:25993290

Genes and abdominal aortic aneurysm.

PubMed

Hinterseher, Irene; Tromp, Gerard; Kuivaniemi, Helena

2011-04-01

Abdominal aortic aneurysm (AAA) is a multifactorial disease with a strong genetic component. Since the first candidate gene studies were published 20 years ago, approximately 100 genetic association studies using single nucleotide polymorphisms (SNPs) in biologically relevant genes have been reported on AAA. These studies investigated SNPs in genes of the extracellular matrix, the cardiovascular system, the immune system, and signaling pathways. Very few studies were large enough to draw firm conclusions and very few results could be replicated in another sample set. The more recent unbiased approaches are family-based DNA linkage studies and genome-wide genetic association studies, which have the potential of identifying the genetic basis for AAA, only when appropriately powered and well-characterized large AAA cohorts are used. SNPs associated with AAA have already been identified in these large multicenter studies. One significant association was of a variant in a gene called contactin-3, which is located on chromosome 3p12.3. However, two follow-up studies could not replicate this association. Two other SNPs, which are located on chromosome 9p21 and 9q33, were replicated in other samples. The two genes with the strongest supporting evidence of contribution to the genetic risk for AAA are the CDKN2BAS gene, also known as ANRIL, which encodes an antisense ribonucleic acid that regulates expression of the cyclin-dependent kinase inhibitors CDKN2A and CDKN2B, and DAB2IP, which encodes an inhibitor of cell growth and survival. Functional studies are now needed to establish the mechanisms by which these genes contribute toward AAA pathogenesis. Copyright © 2011 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.

m-AAA proteases, mitochondrial calcium homeostasis and neurodegeneration

PubMed Central

Patron, Maria; Sprenger, Hans-Georg; Langer, Thomas

2018-01-01

The function of mitochondria depends on ubiquitously expressed and evolutionary conserved m-AAA proteases in the inner membrane. These ATP-dependent peptidases form hexameric complexes built up of homologous subunits. AFG3L2 subunits assemble either into homo-oligomeric isoenzymes or with SPG7 (paraplegin) subunits into hetero-oligomeric proteolytic complexes. Mutations in AFG3L2 are associated with dominant spinocerebellar ataxia (SCA28) characterized by the loss of Purkinje cells, whereas mutations in SPG7 cause a recessive form of hereditary spastic paraplegia (HSP7) with motor neurons of the cortico-spinal tract being predominantly affected. Pleiotropic functions have been assigned to m-AAA proteases, which act as quality control and regulatory enzymes in mitochondria. Loss of m-AAA proteases affects mitochondrial protein synthesis and respiration and leads to mitochondrial fragmentation and deficiencies in the axonal transport of mitochondria. Moreover m-AAA proteases regulate the assembly of the mitochondrial calcium uniporter (MCU) complex. Impaired degradation of the MCU subunit EMRE in AFG3L2-deficient mitochondria results in the formation of deregulated MCU complexes, increased mitochondrial calcium uptake and increased vulnerability of neurons for calcium-induced cell death. A reduction of calcium influx into the cytosol of Purkinje cells rescues ataxia in an AFG3L2-deficient mouse model. In this review, we discuss the relationship between the m-AAA protease and mitochondrial calcium homeostasis and its relevance for neurodegeneration and describe a novel mouse model lacking MCU specifically in Purkinje cells. Our results pledge for a novel view on m-AAA proteases that integrates their pleiotropic functions in mitochondria to explain the pathogenesis of associated neurodegenerative disorders. PMID:29451229

Arg753gln and Arg677 Trp Polymorphisms of Toll-Like Receptor 2 In Acute Apical Abscess.

PubMed

Miri-Moghaddam, Ebrahim; Farhad Mollashahi, Narges; Naghibi, Nava; Garme, Yasaman; Bazi, Ali

2018-06-01

Genetic polymorphisms can alter immunity response against pathogens, which in turn influence individuals' susceptibility to certain infections. Our aim was to determine the association of Arg753Gln (rs5743708) and Arg677Trp (rs12191786) polymorphisms of toll like receptor-2 gene with the two clinical forms of apical periodontitis: acute apical abscess (AAA) and asymptomatic apical periodontitis (AAP). There were 50 patients with AAA as case group and 50 with AAP as control group. Genotyping was done using Tetra-ARMS (amplification refractory mutation system) PCR. Heterozygous genotype of Arg677Trp polymorphism was associated with risk of AAA (OR=1.9, 95% CI: 0.7-5.5, p = 0.05). Although statistically insignificant, Arg677Trp polymorphism promoted the risk of AAA in dominant model (OR=2.1, 95% CI: 0.7-5.9, p > 0.05). The frequency of mutant allele (T) of Arg677Trp polymorphism was higher in AAA (14%) than AAP (7%) subjects (OR=1.7, 95% CI: 0.6-4.7). For Arg753Gln polymorphism, wild homozygous (GG) represented the dominant genotype in both cases (96%) and controls (100%). Variant allele (A) of Arg753Gln polymorphism was identified in 2% of AAA, while no individual represented with this allele in AAP subjects. Individuals with Arg753Gln; Arg677Trp (GG; TC) combination showed an elevated risk of AAA (OR=1.6, 95% CI: 0.5- 4.2, p > 0.05). Arg677Trp polymorphism of TLR-2 rendered a higher risk for the development of abscesses in apical periodontitis. It is recommended to explore role of this polymorphism in other populations.

Structure determination of disease associated peak AAA from l-Tryptophan implicated in the eosinophilia-myalgia syndrome.

PubMed

Klarskov, Klaus; Gagnon, Hugo; Boudreault, Pierre-Luc; Normandin, Chad; Plancq, Baptiste; Marsault, Eric; Gleich, Gerald J; Naylor, Stephen

2018-01-05

The eosinophilia-myalgia syndrome (EMS) outbreak of 1989 that occurred in the USA and elsewhere was caused by the ingestion of l-Tryptophan (L-Trp) solely manufactured by the Japanese company Showa Denko K.K. (SD). Six compounds present in the SD L-Trp were reported to be case-associated contaminants. However, "one" of these compounds, Peak AAA has remained structurally uncharacterized, despite the fact that it was described as "the only statistically significant (p=0.0014) contaminant". Here, we employ on-line microcapillary-high performance liquid chromatography-electrospray ionization mass spectrometry (LC-MS), and tandem mass spectrometry (MS/MS) to determine that Peak AAA is in fact two structurally related isomers. Peak AAA 1 and Peak AAA 2 differed in LC retention times, and were determined by accurate mass-LC-MS to both have a protonated molecular ion (MH +) of mass 343.239Da (Da), corresponding to a molecular formula of C 21 H 30 N 2 O 2, and possessing eight degrees of unsaturation (DoU) for the non-protonated molecule. By comparing the LC-MS and LC-MS-MS retention times and spectra with authentic synthetic standards, Peak AAA 1 was identified as the intermolecular condensation product of L-Trp with anteiso 7-methylnonanoic acid, to afford (S)-2-amino-3-(2-((S,E)-7-methylnon-1-en-1-yl)-1H-indol-3-yl)propanoic acid. Peak AAA 2 was determined to be a condensation product of L-Trp with decanoic acid, which produced (S)-2-amino-3-(2-((E)-dec-1-en-1-yl)-1H-indol-3-yl)propanoic acid. Copyright © 2017 Elsevier B.V. All rights reserved.

Meiotic Clade AAA ATPases: Protein Polymer Disassembly Machines.

PubMed

Monroe, Nicole; Hill, Christopher P

2016-05-08

Meiotic clade AAA ATPases (ATPases associated with diverse cellular activities), which were initially grouped on the basis of phylogenetic classification of their AAA ATPase cassette, include four relatively well characterized family members, Vps4, spastin, katanin and fidgetin. These enzymes all function to disassemble specific polymeric protein structures, with Vps4 disassembling the ESCRT-III polymers that are central to the many membrane-remodeling activities of the ESCRT (endosomal sorting complexes required for transport) pathway and spastin, katanin p60 and fidgetin affecting multiple aspects of cellular dynamics by severing microtubules. They share a common domain architecture that features an N-terminal MIT (microtubule interacting and trafficking) domain followed by a single AAA ATPase cassette. Meiotic clade AAA ATPases function as hexamers that can cycle between the active assembly and inactive monomers/dimers in a regulated process, and they appear to disassemble their polymeric substrates by translocating subunits through the central pore of their hexameric ring. Recent studies with Vps4 have shown that nucleotide-induced asymmetry is a requirement for substrate binding to the pore loops and that recruitment to the protein lattice via MIT domains also relieves autoinhibition and primes the AAA ATPase cassettes for substrate binding. The most striking, unifying feature of meiotic clade AAA ATPases may be their MIT domain, which is a module that is found in a wide variety of proteins that localize to ESCRT-III polymers. Spastin also displays an adjacent microtubule binding sequence, and the presence of both ESCRT-III and microtubule binding elements may underlie the recent findings that the ESCRT-III disassembly function of Vps4 and the microtubule-severing function of spastin, as well as potentially katanin and fidgetin, are highly coordinated. Copyright © 2015 Elsevier Ltd. All rights reserved.

Structural dynamics of the MecA-ClpC complex: a type II AAA+ protein unfolding machine.

PubMed

Liu, Jing; Mei, Ziqing; Li, Ningning; Qi, Yutao; Xu, Yanji; Shi, Yigong; Wang, Feng; Lei, Jianlin; Gao, Ning

2013-06-14

The MecA-ClpC complex is a bacterial type II AAA(+) molecular machine responsible for regulated unfolding of substrates, such as transcription factors ComK and ComS, and targeting them to ClpP for degradation. The six subunits of the MecA-ClpC complex form a closed barrel-like structure, featured with three stacked rings and a hollow passage, where substrates are threaded and translocated through successive pores. Although the general concepts of how polypeptides are unfolded and translocated by internal pore loops of AAA(+) proteins have long been conceived, the detailed mechanistic model remains elusive. With cryoelectron microscopy, we captured four different structures of the MecA-ClpC complexes. These complexes differ in the nucleotide binding states of the two AAA(+) rings and therefore might presumably reflect distinctive, representative snapshots from a dynamic unfolding cycle of this hexameric complex. Structural analysis reveals that nucleotide binding and hydrolysis modulate the hexameric complex in a number of ways, including the opening of the N-terminal ring, the axial and radial positions of pore loops, the compactness of the C-terminal ring, as well as the relative rotation between the two nucleotide-binding domain rings. More importantly, our structural and biochemical data indicate there is an active allosteric communication between the two AAA(+) rings and suggest that concerted actions of the two AAA(+) rings are required for the efficiency of the substrate unfolding and translocation. These findings provide important mechanistic insights into the dynamic cycle of the MecA-ClpC unfoldase and especially lay a foundation toward the complete understanding of the structural dynamics of the general type II AAA(+) hexamers.

m-AAA proteases, mitochondrial calcium homeostasis and neurodegeneration.

PubMed

Patron, Maria; Sprenger, Hans-Georg; Langer, Thomas

2018-03-01

The function of mitochondria depends on ubiquitously expressed and evolutionary conserved m-AAA proteases in the inner membrane. These ATP-dependent peptidases form hexameric complexes built up of homologous subunits. AFG3L2 subunits assemble either into homo-oligomeric isoenzymes or with SPG7 (paraplegin) subunits into hetero-oligomeric proteolytic complexes. Mutations in AFG3L2 are associated with dominant spinocerebellar ataxia (SCA28) characterized by the loss of Purkinje cells, whereas mutations in SPG7 cause a recessive form of hereditary spastic paraplegia (HSP7) with motor neurons of the cortico-spinal tract being predominantly affected. Pleiotropic functions have been assigned to m-AAA proteases, which act as quality control and regulatory enzymes in mitochondria. Loss of m-AAA proteases affects mitochondrial protein synthesis and respiration and leads to mitochondrial fragmentation and deficiencies in the axonal transport of mitochondria. Moreover m-AAA proteases regulate the assembly of the mitochondrial calcium uniporter (MCU) complex. Impaired degradation of the MCU subunit EMRE in AFG3L2-deficient mitochondria results in the formation of deregulated MCU complexes, increased mitochondrial calcium uptake and increased vulnerability of neurons for calcium-induced cell death. A reduction of calcium influx into the cytosol of Purkinje cells rescues ataxia in an AFG3L2-deficient mouse model. In this review, we discuss the relationship between the m-AAA protease and mitochondrial calcium homeostasis and its relevance for neurodegeneration and describe a novel mouse model lacking MCU specifically in Purkinje cells. Our results pledge for a novel view on m-AAA proteases that integrates their pleiotropic functions in mitochondria to explain the pathogenesis of associated neurodegenerative disorders.

Attitude towards one's illness vs. attitude towards a surgical operation, displayed by patients diagnosed with asymptomatic abdominal aortic aneurysm and asymptomatic internal carotid artery stenosis.

PubMed

Stanisić, M; Rzepa, T

2012-08-01

Two most frequent asymptomatic diseases qualifying for vascular surgery are abdominal aortic aneurysm (AAA) and internal carotid artery stenosis (ICAS). Emotions experienced by the patient activate processes of dealing with the cognitive dissonance of asymptomatic disease. The aim of this paper was to compare the reasons involved in decision making on surgery in two asymptomatic vascular pathologies. Fifty patients were divided into two groups: the ICAS group-27 (CAS or CEA) and the AAA group-23 (EVAR or open surgical operation (OSR). Specific questionnaire regarding: 1) self-image; 2) attitude to one's illness; 3) reasons for decision on surgery was applied for the study. The χ² test was used to for the analysis. The AAA patients reacted emotionally (88.2%) comparing to ICAS patients reacting "rationally" (59.3%) (α=0.05). In AAA patients attitude towards themselves had worsened (α=0.001) AAA patients were less likely to seek support in decision on surgery (α=0.01). ICAS patients are internally motivated (78.7%), whereas AAA patients are externally motivated (63.9%) (α=0.001). Reasons underlying the decision on surgery, were predominantly rational (55.8%). In the process of decision-making on surgery by asymptomatic patients, evolutionary transformation takes place - the emotional attitude to one's illness leads to rationally evaluated decision. Regardless of the causes the process of making a decision on surgical operation tended to run more smoothly in ICAS patients. The ICAS patients tended to display a rational attitude to their illness. AAA patients displayed a distinctly emotional attitude towards their illness.

Numerical design and optimization of hydraulic resistance and wall shear stress inside pressure-driven microfluidic networks.

PubMed

Damiri, Hazem Salim; Bardaweel, Hamzeh Khalid

2015-11-07

Microfluidic networks represent the milestone of microfluidic devices. Recent advancements in microfluidic technologies mandate complex designs where both hydraulic resistance and pressure drop across the microfluidic network are minimized, while wall shear stress is precisely mapped throughout the network. In this work, a combination of theoretical and modeling techniques is used to construct a microfluidic network that operates under minimum hydraulic resistance and minimum pressure drop while constraining wall shear stress throughout the network. The results show that in order to minimize the hydraulic resistance and pressure drop throughout the network while maintaining constant wall shear stress throughout the network, geometric and shape conditions related to the compactness and aspect ratio of the parent and daughter branches must be followed. Also, results suggest that while a "local" minimum hydraulic resistance can be achieved for a geometry with an arbitrary aspect ratio, a "global" minimum hydraulic resistance occurs only when the aspect ratio of that geometry is set to unity. Thus, it is concluded that square and equilateral triangular cross-sectional area microfluidic networks have the least resistance compared to all rectangular and isosceles triangular cross-sectional microfluidic networks, respectively. Precise control over wall shear stress through the bifurcations of the microfluidic network is demonstrated in this work. Three multi-generation microfluidic network designs are considered. In these three designs, wall shear stress in the microfluidic network is successfully kept constant, increased in the daughter-branch direction, or decreased in the daughter-branch direction, respectively. For the multi-generation microfluidic network with constant wall shear stress, the design guidelines presented in this work result in identical profiles of wall shear stresses not only within a single generation but also through all the generations of the microfluidic network under investigation. The results obtained in this work are consistent with previously reported data and suitable for a wide range of lab-on-chip applications.

The role of IL-6 in pathogenesis of abdominal aortic aneurysm in mice.

PubMed

Nishihara, Michihide; Aoki, Hiroki; Ohno, Satoko; Furusho, Aya; Hirakata, Saki; Nishida, Norifumi; Ito, Sohei; Hayashi, Makiko; Imaizumi, Tsutomu; Fukumoto, Yoshihiro

2017-01-01

Although the pathogenesis of abdominal aortic aneurysm (AAA) remains unclear, evidence is accumulating to support a central role for inflammation. Inflammatory responses are coordinated by various soluble cytokines of which IL-6 is one of the major proinflammatory cytokines. In this study we examined the role of IL-6 in the pathogenesis of experimental AAA induced by a periaortic exposure to CaCl2 in mice. We now report that the administration of MR16-1, a neutralizing monoclonal antibody specific for the mouse IL-6 receptor, mildly suppressed the development of AAA. The inhibition of IL-6 signaling provoked by MR16-1 also resulted in a suppression of Stat3 activity. Conversely, no significant changes in either NFκB activity, Jnk activity or the expression of matrix metalloproteinases (Mmp) -2 and -9 were identified. Transcriptome analyses revealed that MR16-1-sensitive genes encode chemokines and their receptors, as well as factors that regulate vascular permeability and cell migration. Imaging cytometric analyses then consistently demonstrated reduced cellular infiltration for MR16-1-treated AAA. These results suggest that IL-6 plays an important but limited role in AAA pathogenesis, and primarily regulates cell migration and infiltration. These data would also suggest that IL-6 activity may play an important role in scenarios of continuous cellular infiltration, possibly including human AAA.

The role of IL-6 in pathogenesis of abdominal aortic aneurysm in mice

PubMed Central

Nishihara, Michihide; Ohno, Satoko; Furusho, Aya; Hirakata, Saki; Nishida, Norifumi; Ito, Sohei; Hayashi, Makiko; Imaizumi, Tsutomu; Fukumoto, Yoshihiro

2017-01-01

Although the pathogenesis of abdominal aortic aneurysm (AAA) remains unclear, evidence is accumulating to support a central role for inflammation. Inflammatory responses are coordinated by various soluble cytokines of which IL-6 is one of the major proinflammatory cytokines. In this study we examined the role of IL-6 in the pathogenesis of experimental AAA induced by a periaortic exposure to CaCl2 in mice. We now report that the administration of MR16-1, a neutralizing monoclonal antibody specific for the mouse IL-6 receptor, mildly suppressed the development of AAA. The inhibition of IL-6 signaling provoked by MR16-1 also resulted in a suppression of Stat3 activity. Conversely, no significant changes in either NFκB activity, Jnk activity or the expression of matrix metalloproteinases (Mmp) -2 and -9 were identified. Transcriptome analyses revealed that MR16-1-sensitive genes encode chemokines and their receptors, as well as factors that regulate vascular permeability and cell migration. Imaging cytometric analyses then consistently demonstrated reduced cellular infiltration for MR16-1-treated AAA. These results suggest that IL-6 plays an important but limited role in AAA pathogenesis, and primarily regulates cell migration and infiltration. These data would also suggest that IL-6 activity may play an important role in scenarios of continuous cellular infiltration, possibly including human AAA. PMID:28982132

Telomerase deficiency in bone marrow-derived cells attenuates angiotensin II-induced abdominal aortic aneurysm formation.

PubMed

Findeisen, Hannes M; Gizard, Florence; Zhao, Yue; Cohn, Dianne; Heywood, Elizabeth B; Jones, Karrie L; Lovett, David H; Howatt, Deborah A; Daugherty, Alan; Bruemmer, Dennis

2011-02-01

Abdominal aortic aneurysms (AAA) are an age-related vascular disease and an important cause of morbidity and mortality. In this study, we sought to determine whether the catalytic component of telomerase, telomerase reverse transcriptase (TERT), modulates angiotensin (Ang) II-induced AAA formation. Low-density lipoprotein receptor-deficient (LDLr-/-) mice were lethally irradiated and reconstituted with bone marrow-derived cells from TERT-deficient (TERT-/-) mice or littermate wild-type mice. Mice were placed on a diet enriched in cholesterol, and AAA formation was quantified after 4 weeks of Ang II infusion. Repopulation of LDLr-/- mice with TERT-/- bone marrow-derived cells attenuated Ang II-induced AAA formation. TERT-deficient recipient mice revealed modest telomere attrition in circulating leukocytes at the study end point without any overt effect of the donor genotype on white blood cell counts. In mice repopulated with TERT-/- bone marrow, aortic matrix metalloproteinase-2 (MMP-2) activity was reduced, and TERT-/- macrophages exhibited decreased expression and activity of MMP-2 in response to stimulation with Ang II. Finally, we demonstrated in transient transfection studies that TERT overexpression activates the MMP-2 promoter in macrophages. TERT deficiency in bone marrow-derived macrophages attenuates Ang II-induced AAA formation in LDLr-/- mice and decreases MMP-2 expression. These results point to a previously unrecognized role of TERT in the pathogenesis of AAA.

Bleaching agent action on color stability, surface roughness and microhardness of composites submitted to accelerated artificial aging.

PubMed

Rattacaso, Raphael Mendes Bezerra; da Fonseca Roberti Garcia, Lucas; Aguilar, Fabiano Gamero; Consani, Simonides; de Carvalho Panzeri Pires-de-Souza, Fernanda

2011-04-01

The purpose of this study was to evaluate the bleaching agent action on color stability, surface roughness and microhardness of composites (Charisma, Filtek Supreme and Heliomolar - A2) submitted to accelerated artificial aging (AAA). A Teflon matrix (12 x 2 mm) was used to fabricate 18 specimens (n=6) which, after polishing (Sof-Lex), were submitted to initial color reading (ΔE), Knoop microhardness (KHN) (50 g/15 s load) and roughness (R(a)) (cut-off 0.25 mm) tests. Afterwards, the samples were submitted to AAA for 384 hours and new color, microhardness and roughness readings were performed. After this, the samples were submitted to daily application (4 weeks) of 16% Carbamide Peroxide (NiteWhite ACP) for 8 hours and kept in artificial saliva for 16 hours. New color, microhardness and roughness readings were made at the end of the cycle, and 15 days after bleaching. Comparison of the ΔE means (2-way ANOVA, Bonferroni, P<.05) indicated clinically unacceptable color alteration for all composites after AAA, but without significant difference. Statistically significant increase in the KHN values after AAA was observed, but without significant alterations 15 days after bleaching. For R(a) there was no statistically significant difference after AAA and 15 days after bleaching. The alterations promoted by the bleaching agent and AAA are material dependent.

Emergence of Clonal Hematopoiesis in the Majority of Patients with Acquired Aplastic Anemia

PubMed Central

Babushok, Daria V.; Perdigones, Nieves; Perin, Juan C.; Olson, Timothy S.; Ye, Wenda; Roth, Jacquelyn J.; Lind, Curt; Cattier, Carine; Li, Yimei; Hartung, Helge; Paessler, Michele E.; Frank, Dale M.; Xie, Hongbo M.; Cross, Shanna; Cockroft, Joshua D.; Podsakoff, Gregory M.; Monos, Dimitrios; Biegel, Jaclyn A.; Mason, Philip J.; Bessler, Monica

2015-01-01

Acquired aplastic anemia (aAA) is a non-malignant disease caused by autoimmune destruction of early hematopoietic cells. Clonal hematopoiesis is a late complication, seen in 20–25% of older patients. We hypothesized that clonal hematopoiesis in aAA is a more general phenomenon, which can arise early in disease even in younger patients. To evaluate clonal hematopoiesis in aAA, we used comparative whole exome sequencing of paired bone marrow and skin in 22 patients. We found somatic mutations in sixteen patients (72.7%) with a median disease duration of 1 year; twelve (66.7%) were patients with pediatriconset aAA. Fifty-eight mutations in 51 unique genes were primarily in pathways of immunity and transcriptional regulation. Most frequently mutated was PIGA, with 7 mutations. Only two mutations were in genes recurrently-mutated in MDS. Two patients had oligoclonal loss of HLA alleles, linking immune escape to clone emergence. Two patients had activating mutations in key signaling pathways (STAT5B(p.N642H), CAMK2G(p.T306M)). Our results suggest that clonal hematopoiesis in aAA is common, with two mechanisms emerging― immune escape and increased proliferation. Our findings expand conceptual understanding of this non-neoplastic blood disorder. Future prospective studies of clonal hematopoiesis in aAA will be critical for understanding outcomes, and for designing personalized treatment strategies. PMID:25800665

2-Aminoadipic acid is a biomarker for diabetes risk

PubMed Central

Wang, Thomas J.; Ngo, Debby; Psychogios, Nikolaos; Dejam, Andre; Larson, Martin G.; Vasan, Ramachandran S.; Ghorbani, Anahita; O’Sullivan, John; Cheng, Susan; Rhee, Eugene P.; Sinha, Sumita; McCabe, Elizabeth; Fox, Caroline S.; O’Donnell, Christopher J.; Ho, Jennifer E.; Florez, Jose C.; Magnusson, Martin; Pierce, Kerry A.; Souza, Amanda L.; Yu, Yi; Carter, Christian; Light, Peter E.; Melander, Olle; Clish, Clary B.; Gerszten, Robert E.

2013-01-01

Improvements in metabolite-profiling techniques are providing increased breadth of coverage of the human metabolome and may highlight biomarkers and pathways in common diseases such as diabetes. Using a metabolomics platform that analyzes intermediary organic acids, purines, pyrimidines, and other compounds, we performed a nested case-control study of 188 individuals who developed diabetes and 188 propensity-matched controls from 2,422 normoglycemic participants followed for 12 years in the Framingham Heart Study. The metabolite 2-aminoadipic acid (2-AAA) was most strongly associated with the risk of developing diabetes. Individuals with 2-AAA concentrations in the top quartile had greater than a 4-fold risk of developing diabetes. Levels of 2-AAA were not well correlated with other metabolite biomarkers of diabetes, such as branched chain amino acids and aromatic amino acids, suggesting they report on a distinct pathophysiological pathway. In experimental studies, administration of 2-AAA lowered fasting plasma glucose levels in mice fed both standard chow and high-fat diets. Further, 2-AAA treatment enhanced insulin secretion from a pancreatic β cell line as well as murine and human islets. These data highlight a metabolite not previously associated with diabetes risk that is increased up to 12 years before the onset of overt disease. Our findings suggest that 2-AAA is a marker of diabetes risk and a potential modulator of glucose homeostasis in humans. PMID:24091325

Assessing heterogeneity in oligomeric AAA+ machines.

PubMed

Sysoeva, Tatyana A

2017-03-01

ATPases Associated with various cellular Activities (AAA+ ATPases) are molecular motors that use the energy of ATP binding and hydrolysis to remodel their target macromolecules. The majority of these ATPases form ring-shaped hexamers in which the active sites are located at the interfaces between neighboring subunits. Structural changes initiate in an active site and propagate to distant motor parts that interface and reshape the target macromolecules, thereby performing mechanical work. During the functioning cycle, the AAA+ motor transits through multiple distinct states. Ring architecture and placement of the catalytic sites at the intersubunit interfaces allow for a unique level of coordination among subunits of the motor. This in turn results in conformational differences among subunits and overall asymmetry of the motor ring as it functions. To date, a large amount of structural information has been gathered for different AAA+ motors, but even for the most characterized of them only a few structural states are known and the full mechanistic cycle cannot be yet reconstructed. Therefore, the first part of this work will provide a broad overview of what arrangements of AAA+ subunits have been structurally observed focusing on diversity of ATPase oligomeric ensembles and heterogeneity within the ensembles. The second part of this review will concentrate on methods that assess structural and functional heterogeneity among subunits of AAA+ motors, thus bringing us closer to understanding the mechanism of these fascinating molecular motors.

2-Aminoadipic acid is a biomarker for diabetes risk.

PubMed

Wang, Thomas J; Ngo, Debby; Psychogios, Nikolaos; Dejam, Andre; Larson, Martin G; Vasan, Ramachandran S; Ghorbani, Anahita; O'Sullivan, John; Cheng, Susan; Rhee, Eugene P; Sinha, Sumita; McCabe, Elizabeth; Fox, Caroline S; O'Donnell, Christopher J; Ho, Jennifer E; Florez, Jose C; Magnusson, Martin; Pierce, Kerry A; Souza, Amanda L; Yu, Yi; Carter, Christian; Light, Peter E; Melander, Olle; Clish, Clary B; Gerszten, Robert E

2013-10-01

Improvements in metabolite-profiling techniques are providing increased breadth of coverage of the human metabolome and may highlight biomarkers and pathways in common diseases such as diabetes. Using a metabolomics platform that analyzes intermediary organic acids, purines, pyrimidines, and other compounds, we performed a nested case-control study of 188 individuals who developed diabetes and 188 propensity-matched controls from 2,422 normoglycemic participants followed for 12 years in the Framingham Heart Study. The metabolite 2-aminoadipic acid (2-AAA) was most strongly associated with the risk of developing diabetes. Individuals with 2-AAA concentrations in the top quartile had greater than a 4-fold risk of developing diabetes. Levels of 2-AAA were not well correlated with other metabolite biomarkers of diabetes, such as branched chain amino acids and aromatic amino acids, suggesting they report on a distinct pathophysiological pathway. In experimental studies, administration of 2-AAA lowered fasting plasma glucose levels in mice fed both standard chow and high-fat diets. Further, 2-AAA treatment enhanced insulin secretion from a pancreatic β cell line as well as murine and human islets. These data highlight a metabolite not previously associated with diabetes risk that is increased up to 12 years before the onset of overt disease. Our findings suggest that 2-AAA is a marker of diabetes risk and a potential modulator of glucose homeostasis in humans.

Inverse Interscale Transport of the Reynolds Shear Stress in Plane Couette Turbulence

NASA Astrophysics Data System (ADS)

Kawata, Takuya; Alfredsson, P. Henrik

2018-06-01

Interscale interaction between small-scale structures near the wall and large-scale structures away from the wall plays an increasingly important role with increasing Reynolds number in wall-bounded turbulence. While the top-down influence from the large- to small-scale structures is well known, it has been unclear whether the small scales near the wall also affect the large scales away from the wall. In this Letter we show that the small-scale near-wall structures indeed play a role to maintain the large-scale structures away from the wall, by showing that the Reynolds shear stress is transferred from small to large scales throughout the channel. This is in contrast to the turbulent kinetic energy transport which is from large to small scales. Such an "inverse" interscale transport of the Reynolds shear stress eventually supports the turbulent energy production at large scales.

Animal-assisted activities in pediatric oncology: results from a survey of top-ranked pediatric oncology hospitals

PubMed Central

Chubak, Jessica; Hawkes, Rene

2015-01-01

Animal-assisted activities (AAA) are increasingly common, yet little is known about practices in pediatric oncology. To address this gap, we surveyed the top twenty pediatric oncology hospitals in the United States in May and June of 2014. Questionnaires were sent via email and generally returned by email or postal mail. Among the nineteen responding hospitals, the 18 that offered AAA to pediatric patients formed the basis of our analysis. All sites had written AAA policies. Most programs were restricted to dogs. At 11 hospitals, children with cancer could participate in AAA activities. Outpatient waiting rooms and individual inpatient rooms were the most common locations for AAA with pediatric oncology patients. Safety precautions varied by hospital, but all required hand sanitation after visits and that animals receive an annual health examination, be on a leash or in a carrier, be ≥1 year old, and not be directly from a shelter. Our findings reveal consistencies and variations in practice that may help other hospitals develop their own programs and researchers identify areas of future study. PMID:26589356

Animal-Assisted Activities: Results From a Survey of Top-Ranked Pediatric Oncology Hospitals.

PubMed

Chubak, Jessica; Hawkes, Rene

2016-07-01

Animal-assisted activities (AAA) are increasingly common, yet little is known about practices in pediatric oncology. To address this gap, we surveyed the top 20 pediatric oncology hospitals in the United States in May and June of 2014. Questionnaires were sent via e-mail and generally returned by e-mail or postal mail. Among the 19 responding hospitals, the 18 that offered AAA to pediatric patients formed the basis of our analysis. All sites had written AAA policies. Most programs were restricted to dogs. At 11 hospitals, children with cancer could participate in AAA activities. Outpatient waiting rooms and individual inpatient rooms were the most common locations for AAA with pediatric oncology patients. Safety precautions varied by hospital, but all required hand sanitation after visits and that animals receive an annual health examination, be on a leash or in a carrier, be ≥1 year old, and not be directly from a shelter. Our findings reveal consistencies and variations in practice that may help other hospitals develop their own programs and researchers identify areas of future study. © 2015 by Association of Pediatric Hematology/Oncology Nurses.

49 CFR 178.47 - Specification 4DS welded stainless steel cylinders for aircraft use.

Code of Federal Regulations, 2010 CFR

2010-10-01

... both with a water capacity of not over 100 pounds and a service pressure of at least 500 but not over... (b) of this section. (f) Wall thickness. The minimum wall thickness must be such that the wall stress...) Calculation for sphere must be made by the formula: S = PD / 4tE Where: S = Wall stress in psi; P = Test...

Stress-strain relationship and seismic performance of cast-in-situ phosphogypsum.

PubMed

Zhang, Yichao; Dai, Shaobin; Weng, Wanlin; Huang, Jun; Su, Ying; Cai, Yue

2017-06-16

Phosphogypsum is a waste by-product during the production of phosphoric acid. It not only occupies landfill, but also pollutes the environment, which becomes an important factor restricting the sustainable development of the phosphate fertilizer industry. Research into cast-in-situ phosphogypsum will greatly promote the comprehensive utilization of stored phosphogypsum. The aim of this study was to clarify the mechanical properties of phosphogypsum. Stress-strain relationships of cast-in-situ phosphogypsum were investigated through axial compressive experiments, and seismic performance of cast-in-situ phosphogypsum walls and aerated-concrete masonry walls were simulated based on the experimental results and using finite element analysis. The results showed that the stress-strain relationship fitted into a polynomial equation. Moreover, the displacement ductility index and the energy dissipation index of cast-in-situ phosphogypsum wall were 6.587 and 3.425, respectively. The stress-strain relationship for earthquake-resistant performance of cast-in-situ phosphogypsum walls is better than that of aerated-concrete masonry walls. The curve of stress-strain relationship and the evaluation of earthquake-resistant performance provide theoretical support for the application of cast-in-situ phosphogypsum in building walls.

Wall shear measurement in sand-water mixture flows

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yucel, O.; Grad, W.H.

1975-07-01

The wall shear stress was measured in clear-water and sand-water mixture flows with the use of a flush-mounting hot-film shear-sensor. Data were obtained with 2 shear-sensors and 2 different sands (d50 = 0.45 mm and d50 = 0.88 mm) with solids concentrations of up to Cmax = 1.6% by vol, and for flow Reynolds number of 10/sup 5/ < RD < 6 x 10/sup 5/. The measured sensor wall shear stresses were compared with the true wall shear stresses obtained with the energy head loss measurements conducted in a pipeline system. The results of the tests in the clear-water flowsmore » confirmed the relationship between the sensor power output, Ps, and the wall shear stress, tauo, given by tauo1/3 = APs + B, in which A and B are calibration coefficients. The tests with the low-concentration sand-water mixtures in a vertical pipe indicated that for the present range of experiments, sensor power outputs with the mixtures exceeded those for clear-water by an average of 5%. It is shown that the shear sensors are delicate but accurate instruments that can be used for the measurement of the wall shear stress. (13 refs.)« less

Response of hot element flush wall gauges in oscillating laminar flow

NASA Technical Reports Server (NTRS)

Giddings, T. A.; Cook, W. J.

1986-01-01

The time dependent response characteristics of flush-mounted hot element gauges used as instruments to measure wall shear stress in unsteady periodic air flows were investigated. The study was initiated because anomalous results were obtained from the gauges in oscillating turbulent flows for the phase relation of the wall shear stress variation, indicating possible gauge response problems. Flat plate laminar oscillating turbulent flows characterized by a mean free stream velocity with a superposed sinusoidal variation were performed. Laminar rather than turbulent flows were studied, because a numerical solution for the phase angle between the free stream velocity and the wall shear stress variation that is known to be correct can be obtained. The focus is on comparing the phase angle indicated by the hot element gauges with corresponding numerical prediction for the phase angle, since agreement would indicate that the hot element gauges faithfully follow the true wall shear stress variation.

Comment to 'Regarding "Diabetes mellitus increases the risk of ruptured abdominal aortic aneurysms"'.

PubMed

Wierzba, Waldemar; Sliwczynski, Andrzej; Pinkas, Jaroslaw; Jawien, Arkadiusz; Karnafel, Waldemar

2018-01-01

This publication is a commentary on the Letter to the Editor by Juliette Raffort and Fabien Lareyre. This article clarifies a number of concerns about the method of calculating the index of prevalence of ruptured abdominal aortic aneurysms (AAA). The method of qualifying patients for the study and the method of calculating the index of prevalence of ruptured AAA in cohorts of diabetic and non-diabetic patients was presented. Most researchers calculate the Index of Prevalence per 100,000 of the general population. This gives the misleading result that diabetes reduces the risk of AAA rupture.We used a method which calculated prevalence per 100,000 with diabetes mellitus and per 100,000 without diabetes mellitus. This method confirms that diabetes mellitus increases the risk of ruptured AAA.

RANKL-mediated osteoclastogenic differentiation of macrophages in the abdominal aorta of angiotensin II-infused apolipoprotein E knockout mice.

PubMed

Tanaka, Teruyoshi; Kelly, Matthew; Takei, Yuichiro; Yamanouchi, Dai

2018-04-20

Osteoclastogenic activation of macrophages (OCG) occurs in human abdominal aortic aneurysms (AAAs) and in calcium chloride-induced degenerative AAAs in mice, which have increased matrix metalloproteinase activity. As the activity of OCG in dissecting aneurysms is not clear, we tested the hypothesis that OCG contributes to angiotensin II (Ang II)-induced dissecting aneurysm (Ang II-induced AAA) in apolipoprotein E knockout mice. AAAs were produced in apolipoprotein E knockout mice via the administration of Ang II. Additionally, receptor activator of nuclear factor kB ligand (RANKL)-neutralizing antibody (5 mg/kg) was administered to one group of mice 7 days prior to Ang II infusion. Aneurysmal sections were probed for presence of RANKL and tartrate-resistant acid phosphatase via immunohistochemistry and immunofluorescence staining. Mouse aortas were also examined for RANKL and matrix metalloproteinase 9 expression via Western blot. In vitro murine vascular smooth muscle cells (MOVAS) and murine macrophages (RAW 264.7) were analyzed for the expression of osteogenic factors via Western blot, qPCR, and flow cytometry in response to Ang II or RANKL stimulation. The signaling pathway that mediates Ang II-induced RANKL expression in MOVAS cells was also investigated via application of TG101348, a Janus kinase 2 (JAK2) inhibitor, and Western blot analysis. Immunohistochemical staining of Ang II-induced AAA sections revealed OCG as evidenced by increased RANKL and tartrate-resistant acid phosphatase expression compared with control mice. Immunofluorescence staining of AAA sections revealed co-localization of vascular smooth muscle cells and RANKL, revealing vascular smooth muscle cells as one potential source of RANKL. Systemic administration of RANKL-neutralizing antibody suppressed Ang II-induced AAA, with significant reduction of the maximum diameter of the abdominal aorta compared with vehicle controls (1.5 ± 0.4 mm vs 2.2 ± 0.2 mm). Ang II (1 μM) treatment induced a significant increase in RANKL messenger RNA expression levels in MOVAS cells compared with the vehicle control (1.0 ± 0.2 vs 2.8 ± 0.2). The activities of JAK2 and signal transducer and activator of transcription 5 (STAT5) were also significantly increased by Ang II treatment. Inhibition of JAK2/STAT5 suppressed Ang II-induced RANKL expression, suggesting the involvement of the JAK2/STAT5 signaling pathway. OCG with increased RANKL expression was present in Ang II-induced AAA, and neutralization of RANKL suppressed AAA formation. As neutralization of RANKL has been used clinically to treat osteoporosis and other osteoclast-related diseases, additional study of the effectiveness of RANKL neutralization in AAA is warranted. Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

75 FR 67973 - Ocean Transportation Intermediary License Applicants

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-04

... Office of Transportation Intermediaries, Federal Maritime Commission, Washington, DC 20573. AAA Cargo, Inc. dba AAA Cargo Express Inc. (OFF), 14536 Roscoe Blvd., Suite 99 & 101, Panorama City, CA 91402...

Home Health Care

MedlinePlus

... neighbors, and your local Area Agency on Aging (AAA) to learn more about the home health care ... and assistance provider or Area Agency on Aging (AAA). For help connecting to these agencies, contact the ...

Respite Care

MedlinePlus

... local church group or area agency on aging (AAA) will even run a formal “Friendly Visitor Program” ... of the cost of respite care. Your local AAA will have more information on whether financial assistance ...

Reciprocal Interactions between Cadmium-Induced Cell Wall Responses and Oxidative Stress in Plants

PubMed Central

Loix, Christophe; Huybrechts, Michiel; Vangronsveld, Jaco; Gielen, Marijke; Keunen, Els; Cuypers, Ann

2017-01-01

Cadmium (Cd) pollution renders many soils across the world unsuited or unsafe for food- or feed-orientated agriculture. The main mechanism of Cd phytotoxicity is the induction of oxidative stress, amongst others through the depletion of glutathione. Oxidative stress can damage lipids, proteins, and nucleic acids, leading to growth inhibition or even cell death. The plant cell has a variety of tools to defend itself against Cd stress. First and foremost, cell walls might prevent Cd from entering and damaging the protoplast. Both the primary and secondary cell wall have an array of defensive mechanisms that can be adapted to cope with Cd. Pectin, which contains most of the negative charges within the primary cell wall, can sequester Cd very effectively. In the secondary cell wall, lignification can serve to immobilize Cd and create a tougher barrier for entry. Changes in cell wall composition are, however, dependent on nutrients and conversely might affect their uptake. Additionally, the role of ascorbate (AsA) as most important apoplastic antioxidant is of considerable interest, due to the fact that oxidative stress is a major mechanism underlying Cd toxicity, and that AsA biosynthesis shares several links with cell wall construction. In this review, modifications of the plant cell wall in response to Cd exposure are discussed. Focus lies on pectin in the primary cell wall, lignification in the secondary cell wall and the importance of AsA in the apoplast. Regarding lignification, we attempt to answer the question whether increased lignification is merely a consequence of Cd toxicity, or rather an elicited defense response. We propose a model for lignification as defense response, with a central role for hydrogen peroxide as substrate and signaling molecule. PMID:29163592

Turbulent Boundary Layer on a Cylinder in Axial Flow

DTIC Science & Technology

1988-09-29

finding the wall shea stress. Finally, ft ;hould be noted that the wall shear stress can be found from the streamwrwise gradient of the mornsntum...somewhat butter collapse than inner scaling, suggesting that the outer flow affects events at the wall. By comparison, the burst frequency in a planar

Army Needs to Improve Controls and Audit Trails for the General Fund Enterprise Business System Acquire-to-Retire Business Process

DTIC Science & Technology

2013-09-13

Event 1.4.4,” August 7, 2012 AAA Attestation Report A-2010-0187- FFM , “General Fund Enterprise Business System - Federal Financial Management...Improvement Act Compliance. Examination of Requirements Through Test Event 1.4.0,” September 14, 2010 AAA Audit Report A-2009-0232- FFM , “General Fund...September 30, 2009 AAA Audit Report A-2009-0231- FFM , “General Fund Enterprise Business System - Federal Financial Management Improvement Act

Readily functionalized AAA-DDD triply hydrogen-bonded motifs.

PubMed

Tong, Feng; Linares-Mendez, Iamnica J; Han, Yi-Fei; Wisner, James A; Wang, Hong-Bo

2018-04-25

Herein we present a new, readily functionalized AAA-DDD hydrogen bond array. A novel AAA monomeric unit (3a-b) was obtained from a two-step synthetic procedure starting with 2-aminonicotinaldehyde via microwave radiation (overall yield of 52-66%). 1H NMR and fluorescence spectroscopy confirmed the complexation event with a calculated association constant of 1.57 × 107 M-1. Likewise, the usefulness of this triple hydrogen bond motif in supramolecular polymerization was demonstrated through viscosity measurements in a crosslinked supramolecular alternating copolymer.

Transformation of the People’s Army of Vietnam, 1954-1975

DTIC Science & Technology

2016-05-26

career. My family, both at home and the Army, are the reason I come to work. vi Acronyms AAA Anti-Aircraft Artillery ARVN Army of the...transformation in response to the United States war effort was the modernization of their Anti-Aircraft Artillery ( AAA ). On 2 March 1965, the United States...the AAA into a capable force, the north sought external support. The DRV turned to the USSR to procure equipment to combat the air threat from the

Live Well

MedlinePlus

... talkHIV Act Against AIDS Get Email Updates on AAA Anonymous Feedback HIV/AIDS Media Infographics Syndicated Content ... talkHIV Act Against AIDS Get Email Updates on AAA Anonymous Feedback HIV/AIDS Media Infographics Syndicated Content ...