APP with Kunitz type protease inhibitor domain (KPI) correlates with neuritic plaque density but not with cortical synaptophysin immunoreactivity in Alzheimer's disease and non-demented aged subjects: a multifactorial analysis.

PubMed

Zhan, S S; Sandbrink, R; Beyreuther, K; Schmitt, H P

1995-01-01

The formation of beta A4 amyloid protein in neuritic plaques in Alzheimer's disease (AD) and advanced age is a complex process that involves a number of both cellular and molecular mechanisms, the interrelations of which are not yet completely understood. We have examined quantitatively, in AD and aged controls an extended spectrum of amyloid plaque-related cellular and molecular factors and the cortical synaptophysin immunoreactivity (synaptic density) in order to check for interrelations between them by multifactorial analysis. In 3 cases of senile dementia of the Alzheimer type (SDAT) aged 72, 80 and 82 years, and 9 controls aged 43-88 (mean age 65) years, the cortical synaptophysin immunoreactivity was assessed, together with the numbers of neurons, astrocytes and microglial cells, senile plaques, of tangle-bearing neurons, and the amount of beta A4 amyloid precursor protein (APP) with and without the Kunitz type serine protease inhibitor (KPI) domain. The main results were: APP including the KPI domain (KPI-APP) correlated with the number of neuritic plaques, regardless of whether they occurred in SDAT or non-demented controls. There was no significant difference in the amount of KPI-APP between SDAT and controls. Conversely, APP695 (without KPI) was significantly reduced in SDAT. KPI-APP did not correlate with the synaptophysin immunoreactivity (RGVA), while APP695 showed a significant correlation with the latter in all evaluations. It also correlated with the neuron counts, which was not true for KPI-APP. These results support previous findings indicating that KPI-APP is an important local factor for amyloid deposition in the neuritic plaques, both in AD and in non-demented aged people. On the contrary, KPI-APP does not seem to be significantly involved in the mechanisms of synaptic change outside of the plaques.

Retention of antimicrobial activity in plaque and saliva following mouthrinse use in vivo.

PubMed

Otten, M P T; Busscher, H J; van der Mei, H C; Abbas, F; van Hoogmoed, C G

2010-01-01

The aim of this study was to determine the contribution of plaque and saliva towards the prolonged activity, also called substantivity, of three antimicrobial mouthrinses (Listerine®, Meridol®, Crest Pro Health®), used in combination with a toothpaste (Prodent Coolmint®). Volunteers brushed for 4 weeks with a toothpaste without antimicrobial claims, while during the last 2 weeks half of the volunteers used an antimicrobial mouthrinse in addition to brushing. At the end of the experimental period, plaque and saliva samples were collected 6 h after oral hygiene, and bacterial concentrations and viabilities were determined. The contribution of plaque and saliva towards substantivity was assessed by combining plaque obtained after mechanical cleaning only with plaque and saliva obtained after additional use of an antimicrobial rinse. Subsequently, resulting viabilities of the combined plaques were determined. The viabilities of plaque samples after additional rinsing with mouthrinses were lower than of plaque obtained after mechanical cleaning only, regardless of the rinse involved. Moreover, plaque collected 6 h after rinsing with antimicrobial mouthrinses contained a surplus of antimicrobial activity. Only Listerine showed decreased viability in saliva, but none of the mouthrinses showed any residual antimicrobial activity in saliva. The findings indicate that plaque left behind after mechanical cleaning contributes to the prolonged substantivity of antimicrobial mouthrinses. Copyright © 2010 S. Karger AG, Basel.

NATURAL HISTORY OF DENTAL PLAQUE ACCUMULATION IN MECHANICALLY VENTILATED ADULTS: A DESCRIPTIVE CORRELATIONAL STUDY

PubMed Central

Jones, Deborah J.; Munro, Cindy L.; Grap, Mary Jo

2011-01-01

Summary Objective The purpose of this study was to describe the pattern of dental plaque accumulation in mechanically ventilated adults. Accumulation of dental plaque and bacterial colonization of the oropharynx is associated with a number of systemic diseases including ventilator associated pneumonia. Research Methodology/Design Data were collected from mechanically ventilated critically ill adults (n=137), enrolled within 24 hours of intubation. Dental plaque, counts of decayed, missing and filled teeth and systemic antibiotic use was assessed on study days 1, 3, 5 and 7. Dental plaque averages per study day, tooth type and tooth location were analyzed. Setting Medical Respiratory, Surgical Trauma and Neuroscience ICU’s of a large tertiary care center in the southeast United States. Results Plaque: All surfaces > 60% plaque coverage from day 1 to day 7; Molars and Premolars contained greatest plaque average >70%. Systemic antibiotic use on day 1 had no significant effect on plaque accumulation on day 3 (p=0.73). Conclusions Patients arrive in critical care units with preexisting oral hygiene issues. Dental plaque tends to accumulate in the posterior teeth (molars and premolars) that may be hard for nurses to visualize and reach; this problem may be exacerbated by endotracheal tubes and other equipment. Knowing accumulation trends of plaque will guide the development of effective oral care protocols. PMID:22014582

Mechanical Interaction of an Expanding Coiled Stent with a Plaque-Containing Arterial Wall: A Finite Element Analysis.

PubMed

Welch, Tré R; Eberhart, Robert C; Banerjee, Subhash; Chuong, Cheng-Jen

2016-03-01

Wall injury is observed during stent expansion within atherosclerotic arteries, related in part to stimulation of the inflammatory process. Wall stress and strain induced by stent expansion can be closely examined by finite element analysis (FEA), thus shedding light on procedure-induced sources of inflammation. The purpose of this work was to use FEA to examine the interaction of a coiled polymer stent with a plaque-containing arterial wall during stent expansion. An asymmetric fibrotic plaque-containing arterial wall model was created from intravascular ultrasound (IVUS) images of a diseased artery. A 3D model for a coil stent at unexpanded state was generated in SolidWorks. They were imported into ANSYS for FEA of combined stent expansion and fibrotic plaque-distortion. We simulated the stent expansion in the plaqued lumen by increasing balloon pressure from 0 to 12 atm in 1 atm step. At increasing pressure, we examined how the expanding stent exerts forces on the fibrotic plaque and vascular wall components, and how the latter collectively resist and balance the expansive forces from the stent. Results show the expanding coiled stent creates high stresses within the plaque and the surrounding fibrotic capsule. Lower stresses were observed in adjacent medial and adventitial layers. High principal strains were observed in plaque and fibrotic capsule. The results suggest fibrotic capsule rupture might occur at localized regions. The FEA/IVUS method can be adapted for routine examination of the effects of the expansion of selected furled stents against IVUS-reconstructed diseased vessels, to improve stent deployment practices.

Respiratory pathogen colonization of dental plaque, the lower airways, and endotracheal tube biofilms during mechanical ventilation.

PubMed

Sands, Kirsty M; Wilson, Melanie J; Lewis, Michael A O; Wise, Matt P; Palmer, Nicki; Hayes, Anthony J; Barnes, Rosemary A; Williams, David W

2017-02-01

In mechanically ventilated patients, the endotracheal tube is an essential interface between the patient and ventilator, but inadvertently, it also facilitates the development of ventilator-associated pneumonia (VAP) by subverting pulmonary host defenses. A number of investigations suggest that bacteria colonizing the oral cavity may be important in the etiology of VAP. The present study evaluated microbial changes that occurred in dental plaque and lower airways of 107 critically ill mechanically ventilated patients. Dental plaque and lower airways fluid was collected during the course of mechanical ventilation, with additional samples of dental plaque obtained during the entirety of patients' hospital stay. A "microbial shift" occurred in dental plaque, with colonization by potential VAP pathogens, namely, Staphylococcus aureus and Pseudomonas aeruginosa in 35 patients. Post-extubation analyses revealed that 70% and 55% of patients whose dental plaque included S aureus and P aeruginosa, respectively, reverted back to having a predominantly normal oral microbiota. Respiratory pathogens were also isolated from the lower airways and within the endotracheal tube biofilms. To the best of our knowledge, this is the largest study to date exploring oral microbial changes during both mechanical ventilation and after recovery from critical illness. Based on these findings, it was apparent that during mechanical ventilation, dental plaque represents a source of potential VAP pathogens. Copyright © 2016 Elsevier Inc. All rights reserved.

Motion Artifact Reduction in Ultrasound Based Thermal Strain Imaging of Atherosclerotic Plaques Using Time Series Analysis

PubMed Central

Dutta, Debaditya; Mahmoud, Ahmed M.; Leers, Steven A.; Kim, Kang

2013-01-01

Large lipid pools in vulnerable plaques, in principle, can be detected using US based thermal strain imaging (US-TSI). One practical challenge for in vivo cardiovascular application of US-TSI is that the thermal strain is masked by the mechanical strain caused by cardiac pulsation. ECG gating is a widely adopted method for cardiac motion compensation, but it is often susceptible to electrical and physiological noise. In this paper, we present an alternative time series analysis approach to separate thermal strain from the mechanical strain without using ECG. The performance and feasibility of the time-series analysis technique was tested via numerical simulation as well as in vitro water tank experiments using a vessel mimicking phantom and an excised human atherosclerotic artery where the cardiac pulsation is simulated by a pulsatile pump. PMID:24808628

Numerical analysis of the hemodynamic effect of plaque ulceration in the stenotic carotid artery bifurcation

NASA Astrophysics Data System (ADS)

Wong, Emily Y.; Milner, Jaques S.; Steinman, David A.; Poepping, Tamie L.; Holdsworth, David W.

2009-02-01

The presence of ulceration in carotid artery plaque is an independent risk factor for thromboembolic stroke. However, the associated pathophysiological mechanisms - in particular the mechanisms related to the local hemodynamics in the carotid artery bifurcation - are not well understood. We investigated the effect of carotid plaque ulceration on the local time-varying three-dimensional flow field using computational fluid dynamics (CFD) models of a stenosed carotid bifurcation geometry, with and without the presence of ulceration. CFD analysis of each model was performed with a spatial finite element discretization of over 150,000 quadratic tetrahedral elements and a temporal discretization of 4800 timesteps per cardiac cycle, to adequately resolve the flow field and pulsatile flow, respectively. Pulsatile flow simulations were iterated for five cardiac cycles to allow for cycle-to-cycle analysis following the damping of initial transients in the solution. Comparison between models revealed differences in flow patterns induced by flow exiting from the region of the ulcer cavity, in particular, to the shape, orientation and helicity of the high velocity jet through the stenosis. The stenotic jet in both models exhibited oscillatory motion, but produced higher levels of phase-ensembled turbulence intensity in the ulcerated model. In addition, enhanced out-of-plane recirculation and helical flow was observed in the ulcerated model. These preliminary results suggest that local fluid behaviour may contribute to the thrombogenic risk associated with plaque ulcerations in the stenotic carotid artery bifurcation.

Plaque and gingivitis in the elderly: a randomized, single-blind clinical trial on the outcome of intensified mechanical or antibacterial oral hygiene measures.

PubMed

Schiffner, Ulrich; Bahr, Mathias; Effenberger, Susanne

2007-12-01

To study the outcome of intensified mechanical oral hygiene compared with the effect of an adjunctive antibacterial mouth rinse on plaque and gingivitis in elderly people. In a randomized, single-blind, 6-month controlled clinical study, 106 subjects, 55 years or older, were divided into four groups: (I) Participants were instructed on improved mechanical oral hygiene, including interdental hygiene; (II) subjects used an antibacterial mouth rinse containing amine and stannous fluoride in addition to their usual oral hygiene practices; (III) both intensive mechanical and antibacterial measures were combined; and (IV) a control group with no specific regimen. Gingivitis and plaque were examined. After 6 months, both plaque and gingivitis scores were significantly lower than at baseline in all groups. Reductions in gingivitis differed significantly between the control group and all other groups but not between the three intervention groups. Only groups with improved mechanical oral hygiene showed significant improvements in plaque scores compared with control. Intensive mechanical oral hygiene resulted in greater plaque reduction than the combination of an antibacterial rinse and usual oral hygiene procedures. Gingivitis was reduced by both intensive oral hygiene and use of the amine/stannous fluoride rinse. Combining intensive mechanical oral hygiene with the antibacterial rinse did not result in further gingivitis reduction.

Quantitative coronary plaque analysis predicts high-risk plaque morphology on coronary computed tomography angiography: results from the ROMICAT II trial.

PubMed

Liu, Ting; Maurovich-Horvat, Pál; Mayrhofer, Thomas; Puchner, Stefan B; Lu, Michael T; Ghemigian, Khristine; Kitslaar, Pieter H; Broersen, Alexander; Pursnani, Amit; Hoffmann, Udo; Ferencik, Maros

2018-02-01

Semi-automated software can provide quantitative assessment of atherosclerotic plaques on coronary CT angiography (CTA). The relationship between established qualitative high-risk plaque features and quantitative plaque measurements has not been studied. We analyzed the association between quantitative plaque measurements and qualitative high-risk plaque features on coronary CTA. We included 260 patients with plaque who underwent coronary CTA in the Rule Out Myocardial Infarction/Ischemia Using Computer Assisted Tomography (ROMICAT) II trial. Quantitative plaque assessment and qualitative plaque characterization were performed on a per coronary segment basis. Quantitative coronary plaque measurements included plaque volume, plaque burden, remodeling index, and diameter stenosis. In qualitative analysis, high-risk plaque was present if positive remodeling, low CT attenuation plaque, napkin-ring sign or spotty calcium were detected. Univariable and multivariable logistic regression analyses were performed to assess the association between quantitative and qualitative high-risk plaque assessment. Among 888 segments with coronary plaque, high-risk plaque was present in 391 (44.0%) segments by qualitative analysis. In quantitative analysis, segments with high-risk plaque had higher total plaque volume, low CT attenuation plaque volume, plaque burden and remodeling index. Quantitatively assessed low CT attenuation plaque volume (odds ratio 1.12 per 1 mm 3 , 95% CI 1.04-1.21), positive remodeling (odds ratio 1.25 per 0.1, 95% CI 1.10-1.41) and plaque burden (odds ratio 1.53 per 0.1, 95% CI 1.08-2.16) were associated with high-risk plaque. Quantitative coronary plaque characteristics (low CT attenuation plaque volume, positive remodeling and plaque burden) measured by semi-automated software correlated with qualitative assessment of high-risk plaque features.

[Expression and antagonist role of endothelin and nitric oxide synthase in atherosclerotic plaque].

PubMed

Song, L; Wang, D; Wang, T

1997-02-01

To study the pathogenetic mechanism of atherosclerotic plaque, the action of mediation and antagonism of endothelin (ET) and nitric oxide synthase (NOS) was investigated. In situ hybridization, RT-PCR on endothelin and NOS, cytochemistry on NOS were measured using the rabbit atherosclerosis model and cultured vascular smooth muscle cells (VSMC) from normal rabbit. Transcription of endothelin mRNA increased and transcription of NOS mRNA decreased in astherosclerotic plaque: compared with normal aorta, expression of ET gene in plaque was increased by 1.2 times and the expression of NOS gene was decreased by 22.2%; cytochemistry combined with image pattern analysis showed that ET could inhibit NOS protien synthesis in VSMC; type A receptor antagonist of ET could inhibit the role of ET which causes a decrease of NOS protein in VSMC. The imbalance between NOS and ET, namely abnormal increase of ET and/or obvious decrease of NOS, is related to atherosclerotic plaque formation.

Structural analysis of two different stent configurations.

PubMed

Simão, M; Ferreira, J M; Mora-Rodriguez, J; Ramos, H M

2017-06-01

Two different stent configurations (i.e. the well known Palmaz-Schatz (PS) and a new stent configuration) are mechanically investigated. A finite element model was used to study the two geometries under combining loads and a computational fluid dynamic model based on fluid structure interaction was developed investigating the plaque and the artery wall reactions in a stented arterial segment. These models determine the stress and displacement fields of the two stents under internal pressure conditions. Results suggested that stent designs cause alterations in vascular anatomy that adversely affect arterial stress distributions within the wall, which have impact in the vessel responses such as the restenosis. The hemodynamic analysis shows the use of new stent geometry suggests better biofluid mechanical response such as the deformation and the progressive amount of plaque growth.

[Evaluation of dental plaque by quantitative digital image analysis system].

PubMed

Huang, Z; Luan, Q X

2016-04-18

To analyze the plaque staining image by using image analysis software, to verify the maneuverability, practicability and repeatability of this technique, and to evaluate the influence of different plaque stains. In the study, 30 volunteers were enrolled from the new dental students of Peking University Health Science Center in accordance with the inclusion criteria. The digital images of the anterior teeth were acquired after plaque stained according to filming standardization.The image analysis was performed using Image Pro Plus 7.0, and the Quigley-Hein plaque indexes of the anterior teeth were evaluated. The plaque stain area percentage and the corresponding dental plaque index were highly correlated,and the Spearman correlation coefficient was 0.776 (P<0.01). Intraclass correlation coefficients of the tooth area and plaque area which two researchers used the software to calculate were 0.956 and 0.930 (P<0.01).The Bland-Altman analysis chart showed only a few spots outside the 95% consistency boundaries. The different plaque stains image analysis results showed that the difference of the tooth area measurements was not significant, while the difference of the plaque area measurements significant (P<0.01). This method is easy in operation and control,highly related to the calculated percentage of plaque area and traditional plaque index, and has good reproducibility.The different plaque staining method has little effect on image segmentation results.The sensitive plaque stain for image analysis is suggested.

IVUS-Based Computational Modeling and Planar Biaxial Artery Material Properties for Human Coronary Plaque Vulnerability Assessment

PubMed Central

Liu, Haofei; Cai, Mingchao; Yang, Chun; Zheng, Jie; Bach, Richard; Kural, Mehmet H.; Billiar, Kristen L.; Muccigrosso, David; Lu, Dongsi; Tang, Dalin

2012-01-01

Image-based computational modeling has been introduced for vulnerable atherosclerotic plaques to identify critical mechanical conditions which may be used for better plaque assessment and rupture predictions. In vivo patient-specific coronary plaque models are lagging due to limitations on non-invasive image resolution, flow data, and vessel material properties. A framework is proposed to combine intravascular ultrasound (IVUS) imaging, biaxial mechanical testing and computational modeling with fluid-structure interactions and anisotropic material properties to acquire better and more complete plaque data and make more accurate plaque vulnerability assessment and predictions. Impact of pre-shrink-stretch process, vessel curvature and high blood pressure on stress, strain, flow velocity and flow maximum principal shear stress was investigated. PMID:22428362

Effects of Low Carbohydrate High Protein (LCHP) diet on atherosclerotic plaque phenotype in ApoE/LDLR-/- mice: FT-IR and Raman imaging.

PubMed

Wrobel, T P; Marzec, K M; Chlopicki, S; Maślak, E; Jasztal, A; Franczyk-Żarów, M; Czyżyńska-Cichoń, I; Moszkowski, T; Kostogrys, R B; Baranska, M

2015-09-22

Low Carbohydrate High Protein (LCHP) diet displays pro-atherogenic effects, however, the exact mechanisms involved are still unclear. Here, with the use of vibrational imaging, such as Fourier transform infrared (FT-IR) and Raman (RS) spectroscopies, we characterize biochemical content of plaques in Brachiocephalic Arteries (BCA) from ApoE/LDLR(-/-) mice fed LCHP diet as compared to control, recomended by American Institute of Nutrition, AIN diet. FT-IR images were taken from 6-10 sections of BCA from each mice and were complemented with RS measurements with higher spatial resolution of chosen areas of plaque sections. In aortic plaques from LCHP fed ApoE/LDLR(-/-) mice, the content of cholesterol and cholesterol esters was increased, while that of proteins was decreased as evidenced by global FT-IR analysis. High resolution imaging by RS identified necrotic core/foam cells, lipids (including cholesterol crystals), calcium mineralization and fibrous cap. The decreased relative thickness of the outer fibrous cap and the presence of buried caps were prominent features of the plaques in ApoE/LDLR(-/-) mice fed LCHP diet. In conclusion, FT-IR and Raman-based imaging provided a complementary insight into the biochemical composition of the plaque suggesting that LCHP diet increased plaque cholesterol and cholesterol esters contents of atherosclerotic plaque, supporting the cholesterol-driven pathogenesis of LCHP-induced atherogenesis.

Plaque levels of patients with fixed orthodontic appliances measured by digital plaque image analysis.

PubMed

Klukowska, Malgorzata; Bader, Annike; Erbe, Christina; Bellamy, Philip; White, Donald J; Anastasia, Mary Kay; Wehrbein, Heiner

2011-05-01

A digital plaque image analysis system was developed to objectively assess dental plaque formation and coverage in patients treated with fixed orthodontic appliances. The technique was used to assess plaque levels of 52 patients undergoing treatment with fixed appliances in the Department of Orthodontics at Johannes Gutenberg University in Mainz, Germany. Plaque levels ranged from 5.1% to 85.3% of the analyzed tooth areas. About 37% of the patients had plaque levels over 50% of the dentition, but only 10% exhibited plaque levels below 15% of tooth coverage. The mean plaque coverage was 41.9% ± 18.8%. Plaque was mostly present along the gum line and around the orthodontic brackets and wires. The digital plaque image analysis system might provide a convenient quantitative technique to assess oral hygiene in orthodontic patients with multi-bracket appliances. Plaque coverage in orthodontic patients is extremely high and is 2 to 3 times higher than levels observed in high plaque-forming adults without appliances participating in clinical studies of the digital plaque image analysis system. Improved hygiene, chemotherapeutic regimens, and compliance are necessary in these patients. Copyright © 2011 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

Short communication: Dating components of human atherosclerotic plaques.

PubMed

Gonçalves, Isabel; Stenström, Kristina; Skog, Göran; Mattsson, Sören; Nitulescu, Mihaela; Nilsson, Jan

2010-04-02

Atherosclerotic plaques that give rise to acute clinical symptoms are typically characterized by degradation of the connective tissue and plaque rupture. Experimental studies have shown that mechanisms to repair vulnerable lesions exist, but the rate of remodeling of human plaque tissue has not been studied. In the present study, we determined the biological age of different components of advanced human atherosclerotic plaques by analyzing tissue levels of (14)C released into the atmosphere during the nuclear weapons tests in the late 1950s and early 1960s. Atherosclerotic plaques were obtained from 10 patients (age 46 to 80 years) undergoing carotid surgery. Different regions of the plaques were dissected and analyzed for (14)C content using accelerator mass spectrometry. At the time of surgery, the mean biological age of the cap region was 6.4+/-3.2 years, which was significantly lower than that of the shoulder region (12.9+/-3.0 years, P<0.01), the interface toward the media (12.4+/-3.3 years, P<0.01), and the core (9.8+/-4.5 years, P<0.05). Analysis of proliferative activity and rate of apoptosis showed no signs of increased cellular turnover in the cap, suggesting that the lower (14)C content reflected a more recent time of formation. These results show that the turnover time of human plaque tissue is very long and may explain why regression of atherosclerotic plaque size rarely is observed in cardiovascular intervention trials.

Use of a Vaccinia Construct Expressing the Circumsporozoite Protein in the Analysis of Protective Immunity to Plasmodium yoelii

DTIC Science & Technology

1988-01-01

William R. Majarian, 2 ,5 Frank A. Robey, 3 Walter Weiss, 1 and Stephen L. Hoffman 1 lInfectious Diseases Department, Naval Medical Research Institute...autoradiography. Recombinant viruses which were positive in this assay were subject to 3 rounds of plaque purification. Finally, plaque purified virus was...mechanisms in the protective immunity elicited by inmunization with irradiated sporozoites (3,7,8,9). In an attempt to induce a protective cellular immune

A Framework for Local Mechanical Characterization of Atherosclerotic Plaques: Combination of Ultrasound Displacement Imaging and Inverse Finite Element Analysis.

PubMed

Akyildiz, Ali C; Hansen, Hendrik H G; Nieuwstadt, Harm A; Speelman, Lambert; De Korte, Chris L; van der Steen, Antonius F W; Gijsen, Frank J H

2016-04-01

Biomechanical models have the potential to predict plaque rupture. For reliable models, correct material properties of plaque components are a prerequisite. This study presents a new technique, where high resolution ultrasound displacement imaging and inverse finite element (FE) modeling is combined, to estimate material properties of plaque components. Iliac arteries with plaques were excised from 6 atherosclerotic pigs and subjected to an inflation test with pressures ranging from 10 to 120 mmHg. The arteries were imaged with high frequency 40 MHz ultrasound. Deformation maps of the plaques were reconstructed by cross correlation of the ultrasound radiofrequency data. Subsequently, the arteries were perfusion fixed for histology and structural components were identified. The histological data were registered to the ultrasound data to construct FE model of the plaques. Material properties of the arterial wall and the intima of the atherosclerotic plaques were estimated using a grid search method. The computed displacement fields showed good agreement with the measured displacement fields, implying that the FE models were able to capture local inhomogeneities within the plaque. On average, nonlinear stiffening of both the wall and the intima was observed, and the wall of the atheroslcerotic porcine iliac arteries was markedly stiffer than the intima (877 ± 459 vs. 100 ± 68 kPa at 100 mmHg). The large spread in the data further illustrates the wide variation of the material properties. We demonstrated the feasibility of a mixed experimental-numerical framework to determine the material properties of arterial wall and intima of atherosclerotic plaques from intact arteries, and concluded that, due to the observed variation, plaque specific properties are required for accurate stress simulations.

Multimodal Chemical Imaging of Amyloid Plaque Polymorphism Reveals Aβ Aggregation Dependent Anionic Lipid Accumulations and Metabolism.

PubMed

Michno, Wojciech; Kaya, Ibrahim; Nyström, Sofie; Guerard, Laurent; Nilsson, K Peter R; Hammarström, Per; Blennow, Kaj; Zetterberg, Henrik; Hanrieder, Jörg

2018-06-01

Amyloid plaque formation constitutes one of the main pathological hallmark of Alzheimer's disease (AD) and is suggested to be a critical factor driving disease pathogenesis. Interestingly, in patients that display amyloid pathology but remain cognitively normal, Aβ deposits are predominantly of diffuse morphology suggesting that cored plaque formation is primarily associated with cognitive deterioration and AD pathogenesis. Little is known about the molecular mechanism responsible for conversion of monomeric Aβ into neurotoxic aggregates and the predominantly cored deposits observed in AD. The structural diversity among Aβ plaques, including cored/compact- and diffuse, may be linked to their distinct Aβ profile and other chemical species including neuronal lipids. We developed a novel, chemical imaging paradigm combining matrix assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) and fluorescent amyloid staining. This multimodal imaging approach was used to probe the lipid chemistry associated with structural plaque heterogeneity in transgenic AD mice (tgAPPSwe) and was correlated to Aβ profiles determined by subsequent laser microdissection and immunoprecipitation-mass spectrometry. Multivariate image analysis revealed an inverse localization of ceramides and their matching metabolites to diffuse and cored structures within single plaques, respectively. Moreover, phosphatidylinositols implicated in AD pathogenesis, were found to localise to the diffuse Aβ structures and correlate with Aβ1-42. Further, lysophospholipids implicated in neuroinflammation were increased in all Aβ deposits. The results support previous clinical findings on the importance of lipid disturbances in AD pathophysiology and associated sphingolipid processing. These data highlight the potential of multimodal imaging as a powerful technology to probe neuropathological mechanisms.

Antimicrobial photodynamic therapy suppresses dental plaque formation in healthy adults: a randomized controlled clinical trial.

PubMed

Ichinose-Tsuno, Akiko; Aoki, Akira; Takeuchi, Yasuo; Kirikae, Teruo; Shimbo, Takuro; Lee, Masaichi-Chang-Il; Yoshino, Fumihiko; Maruoka, Yutaka; Itoh, Toshiyuki; Ishikawa, Isao; Izumi, Yuichi

2014-12-15

Oral care is important for oral and systemic health, especially for elderly institutionalized individuals and compromised patients. However, conventional mechanical plaque control is often difficult for these patients because of the pain or the risk of aspiration. Although antimicrobial photodynamic therapy (aPDT), which is considered an alternative or adjunct to mechanical approaches, has potential application as a less stressful method of daily plaque control, no clinical application of this technique has been reported. We investigated the inhibitory effect of a combination of toluidine blue O (TBO), and a red light-emitting diode (LED) on dental plaque formation in healthy volunteers. The optimal concentration of TBO was determined in preliminary in vitro experiments to evaluate the bactericidal effect of aPDT on Streptococcus oralis and to clarify its safety in fibroblast cells. To survey the mechanism of TBO-mediated aPDT, the quality and quantity of reactive oxygen species (ROS) generated during aPDT were also examined using electron spin resonance (ESR) spectroscopy. Subsequently, the inhibitory effect of aPDT on dental plaque formation was investigated in eleven subjects as a clinical pilot study. The right or left mandibular premolars were randomly assigned to the treatment (with aPDT) or control (without aPDT) groups. In total, aPDT was applied six times (twice per day) to the teeth in the test group over a period of four days. On the fourth day, the study concluded and the analyses were performed. A combination of 500 or 1000 μg/ml TBO and LED irradiation for 20 s significantly decreased the number of colony forming units of Streptococcus oralis. The cytotoxicity of aPDT was comparable to that of standard antiseptics used in the oral cavity. Hydroxyl radicals were detected by ESR analysis, but singlet oxygen was not. A randomized controlled trial demonstrated that aPDT with 1000 μg/ml TBO and red LED irradiation significantly suppressed dental plaque formation without harming teeth or the surrounding tissues. aPDT has the potential to be a promising novel technical modality for dental plaque control. This trial was registered with University Hospital Medical Information Network Clinical Trials Registry (number UMIN000012504).

Optical measurement of arterial mechanical properties: from atherosclerotic plaque initiation to rupture

NASA Astrophysics Data System (ADS)

Nadkarni, Seemantini K.

2013-12-01

During the pathogenesis of coronary atherosclerosis, from lesion initiation to rupture, arterial mechanical properties are altered by a number of cellular, molecular, and hemodynamic processes. There is growing recognition that mechanical factors may actively drive vascular cell signaling and regulate atherosclerosis disease progression. In advanced plaques, the mechanical properties of the atheroma influence stress distributions in the fibrous cap and mediate plaque rupture resulting in acute coronary events. This review paper explores current optical technologies that provide information on the mechanical properties of arterial tissue to advance our understanding of the mechanical factors involved in atherosclerosis development leading to plaque rupture. The optical approaches discussed include optical microrheology and traction force microscopy that probe the mechanical behavior of single cell and extracellular matrix components, and intravascular imaging modalities including laser speckle rheology, optical coherence elastography, and polarization-sensitive optical coherence tomography to measure the mechanical properties of advanced coronary lesions. Given the wealth of information that these techniques can provide, optical imaging modalities are poised to play an increasingly significant role in elucidating the mechanical aspects of coronary atherosclerosis in the future.

Assessment of atherosclerotic plaque collagen content and architecture using polarization-sensitive optical coherence tomography (Conference Presentation)

NASA Astrophysics Data System (ADS)

Doradla, Pallavi; Villiger, Martin; Tshikudi, Diane M.; Bouma, Brett E.; Nadkarni, Seemantini K.

2016-02-01

Acute myocardial infarction, caused by the rupture of vulnerable coronary plaques, is the leading cause of death worldwide. Collagen is the primary extracellular matrix macromolecule that imparts the mechanical stability to a plaque and its reduction causes plaque instability. Intracoronary polarization sensitive optical coherence tomography (PS-OCT) measures the polarization states of the backscattered light from the tissue to evaluate plaque birefringence, a material property that is elevated in proteins such as collagen with an ordered structure. Here we investigate the dependence of the PS-OCT parameters on the quantity of the plaque collagen and fiber architecture. In this study, coronary arterial segments from human cadaveric hearts were evaluated with intracoronary PS-OCT and compared with Histopathological assessment of collagen content and architecture from picrosirius-red (PSR) stained sections. PSR sections were visualized with circularly-polarized light microscopy to quantify collagen birefringence, and the additional assessment of color hue indicated fibril thickness. Due to the ordered architecture of thick collagen fibers, a positive correlation between PS-OCT retardation and quantity of thick collagen fibers (r=0.54, p=0.04), and similarly with the total collagen content (r=0.51, p=0.03) was observed. In contrast, there was no perceivable relationship between PS-OCT retardation and the presence of thin collagen fibers (r=0.08, p=0.07), suggesting that thin and disorganized collagen fiber architecture did not significantly contribute to the PS-OCT retardation. Further analysis will be performed to assess the relationship between PS-OCT retardation and collagen architecture based on immunohistochemical analysis of collagen type. These results suggest that intracoronary PS-OCT may open the opportunity to assess collagen architecture in addition total collagen content, potentially enabling an improved understanding of coronary plaque rupture.

Graphical modeling of gene expression in monocytes suggests molecular mechanisms explaining increased atherosclerosis in smokers.

PubMed

Verdugo, Ricardo A; Zeller, Tanja; Rotival, Maxime; Wild, Philipp S; Münzel, Thomas; Lackner, Karl J; Weidmann, Henri; Ninio, Ewa; Trégouët, David-Alexandre; Cambien, François; Blankenberg, Stefan; Tiret, Laurence

2013-01-01

Smoking is a risk factor for atherosclerosis with reported widespread effects on gene expression in circulating blood cells. We hypothesized that a molecular signature mediating the relation between smoking and atherosclerosis may be found in the transcriptome of circulating monocytes. Genome-wide expression profiles and counts of atherosclerotic plaques in carotid arteries were collected in 248 smokers and 688 non-smokers from the general population. Patterns of co-expressed genes were identified by Independent Component Analysis (ICA) and network structure of the pattern-specific gene modules was inferred by the PC-algorithm. A likelihood-based causality test was implemented to select patterns that fit models containing a path "smoking→gene expression→plaques". Robustness of the causal inference was assessed by bootstrapping. At a FDR ≤0.10, 3,368 genes were associated to smoking or plaques, of which 93% were associated to smoking only. SASH1 showed the strongest association to smoking and PPARG the strongest association to plaques. Twenty-nine gene patterns were identified by ICA. Modules containing SASH1 and PPARG did not show evidence for the "smoking→gene expression→plaques" causality model. Conversely, three modules had good support for causal effects and exhibited a network topology consistent with gene expression mediating the relation between smoking and plaques. The network with the strongest support for causal effects was connected to plaques through SLC39A8, a gene with known association to HDL-cholesterol and cellular uptake of cadmium from tobacco, while smoking was directly connected to GAS6, a gene reported to have anti-inflammatory effects in atherosclerosis and to be up-regulated in the placenta of women smoking during pregnancy. Our analysis of the transcriptome of monocytes recovered genes relevant for association to smoking and atherosclerosis, and connected genes that before, were only studied in separate contexts. Inspection of correlation structure revealed candidates that would be missed by expression-phenotype association analysis alone.

A vascular biology network model focused on inflammatory processes to investigate atherogenesis and plaque instability

PubMed Central

2014-01-01

Background Numerous inflammation-related pathways have been shown to play important roles in atherogenesis. Rapid and efficient assessment of the relative influence of each of those pathways is a challenge in the era of “omics” data generation. The aim of the present work was to develop a network model of inflammation-related molecular pathways underlying vascular disease to assess the degree of translatability of preclinical molecular data to the human clinical setting. Methods We constructed and evaluated the Vascular Inflammatory Processes Network (V-IPN), a model representing a collection of vascular processes modulated by inflammatory stimuli that lead to the development of atherosclerosis. Results Utilizing the V-IPN as a platform for biological discovery, we have identified key vascular processes and mechanisms captured by gene expression profiling data from four independent datasets from human endothelial cells (ECs) and human and murine intact vessels. Primary ECs in culture from multiple donors revealed a richer mapping of mechanisms identified by the V-IPN compared to an immortalized EC line. Furthermore, an evaluation of gene expression datasets from aortas of old ApoE-/- mice (78 weeks) and human coronary arteries with advanced atherosclerotic lesions identified significant commonalities in the two species, as well as several mechanisms specific to human arteries that are consistent with the development of unstable atherosclerotic plaques. Conclusions We have generated a new biological network model of atherogenic processes that demonstrates the power of network analysis to advance integrative, systems biology-based knowledge of cross-species translatability, plaque development and potential mechanisms leading to plaque instability. PMID:24965703

Biomechanics of Atherosclerotic Coronary Plaque: Site, Stability and In Vivo Elasticity Modeling

PubMed Central

Ohayon, Jacques; Finet, Gérard; Le Floc’h, Simon; Cloutier, Guy; Gharib, Ahmed M.; Heroux, Julie; Pettigrew, Roderic I.

2016-01-01

Coronary atheroma develop in local sites that are widely variable among patients and are considerably variable in their vulnerability for rupture. This article summarizes studies conducted by our collaborative laboratories on predictive biomechanical modeling of coronary plaques. It aims to give insights into the role of biomechanics in the development and localization of atherosclerosis, the morphologic features that determine vulnerable plaque stability, and emerging in vivo imaging techniques that may detect and characterize vulnerable plaque. Composite biomechanical and hemodynamic factors that influence the actual site of development of plaques have been studied. Plaque vulnerability, in vivo, is more challenging to assess. Important steps have been made in defining the biomechanical factors that are predictive of plaque rupture and the likelihood of this occurring if characteristic features are known. A critical key in defining plaque vulnerability is the accurate quantification of both the morphology and the mechanical properties of the diseased arteries. Recently, an early IVUS based palpography technique developed to assess local strain, elasticity and mechanical instabilities has been successfully revisited and improved to account for complex plaque geometries. This is based on an initial best estimation of the plaque components’ contours, allowing subsequent iteration for elastic modulus assessment as a basis for plaque stability determination. The improved method has also been preliminarily evaluated in patients with successful histologic correlation. Further clinical evaluation and refinement are on the horizon. PMID:24043605

Plaque echodensity and textural features are associated with histologic carotid plaque instability.

PubMed

Doonan, Robert J; Gorgui, Jessica; Veinot, Jean P; Lai, Chi; Kyriacou, Efthyvoulos; Corriveau, Marc M; Steinmetz, Oren K; Daskalopoulou, Stella S

2016-09-01

Carotid plaque echodensity and texture features predict cerebrovascular symptomatology. Our purpose was to determine the association of echodensity and textural features obtained from a digital image analysis (DIA) program with histologic features of plaque instability as well as to identify the specific morphologic characteristics of unstable plaques. Patients scheduled to undergo carotid endarterectomy were recruited and underwent carotid ultrasound imaging. DIA was performed to extract echodensity and textural features using Plaque Texture Analysis software (LifeQ Medical Ltd, Nicosia, Cyprus). Carotid plaque surgical specimens were obtained and analyzed histologically. Principal component analysis (PCA) was performed to reduce imaging variables. Logistic regression models were used to determine if PCA variables and individual imaging variables predicted histologic features of plaque instability. Image analysis data from 160 patients were analyzed. Individual imaging features of plaque echolucency and homogeneity were associated with a more unstable plaque phenotype on histology. These results were independent of age, sex, and degree of carotid stenosis. PCA reduced 39 individual imaging variables to five PCA variables. PCA1 and PCA2 were significantly associated with overall plaque instability on histology (both P = .02), whereas PCA3 did not achieve statistical significance (P = .07). DIA features of carotid plaques are associated with histologic plaque instability as assessed by multiple histologic features. Importantly, unstable plaques on histology appear more echolucent and homogeneous on ultrasound imaging. These results are independent of stenosis, suggesting that image analysis may have a role in refining the selection of patients who undergo carotid endarterectomy. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

In vivo serial MRI-based models and statistical methods to quantify sensitivity and specificity of mechanical predictors for carotid plaque rupture: location and beyond.

PubMed

Wu, Zheyang; Yang, Chun; Tang, Dalin

2011-06-01

It has been hypothesized that mechanical risk factors may be used to predict future atherosclerotic plaque rupture. Truly predictive methods for plaque rupture and methods to identify the best predictor(s) from all the candidates are lacking in the literature. A novel combination of computational and statistical models based on serial magnetic resonance imaging (MRI) was introduced to quantify sensitivity and specificity of mechanical predictors to identify the best candidate for plaque rupture site prediction. Serial in vivo MRI data of carotid plaque from one patient was acquired with follow-up scan showing ulceration. 3D computational fluid-structure interaction (FSI) models using both baseline and follow-up data were constructed and plaque wall stress (PWS) and strain (PWSn) and flow maximum shear stress (FSS) were extracted from all 600 matched nodal points (100 points per matched slice, baseline matching follow-up) on the lumen surface for analysis. Each of the 600 points was marked "ulcer" or "nonulcer" using follow-up scan. Predictive statistical models for each of the seven combinations of PWS, PWSn, and FSS were trained using the follow-up data and applied to the baseline data to assess their sensitivity and specificity using the 600 data points for ulcer predictions. Sensitivity of prediction is defined as the proportion of the true positive outcomes that are predicted to be positive. Specificity of prediction is defined as the proportion of the true negative outcomes that are correctly predicted to be negative. Using probability 0.3 as a threshold to infer ulcer occurrence at the prediction stage, the combination of PWS and PWSn provided the best predictive accuracy with (sensitivity, specificity) = (0.97, 0.958). Sensitivity and specificity given by PWS, PWSn, and FSS individually were (0.788, 0.968), (0.515, 0.968), and (0.758, 0.928), respectively. The proposed computational-statistical process provides a novel method and a framework to assess the sensitivity and specificity of various risk indicators and offers the potential to identify the optimized predictor for plaque rupture using serial MRI with follow-up scan showing ulceration as the gold standard for method validation. While serial MRI data with actual rupture are hard to acquire, this single-case study suggests that combination of multiple predictors may provide potential improvement to existing plaque assessment schemes. With large-scale patient studies, this predictive modeling process may provide more solid ground for rupture predictor selection strategies and methods for image-based plaque vulnerability assessment.

Evidence HDAC9 genetic variant associated with ischaemic stroke increases risk via promoting carotid atherosclerosis

PubMed Central

Markus, Hugh S; Mäkelä, Kari-Matti; Bevan, Steve; Raitoharju, Emma; Oksala, Niku; Bis, Joshua C.; O’Donnell, Chris; Hainsworth, Atticus; Lehtimäki, Terho

2014-01-01

Background and purpose A novel association between a single nucleotide polymorphism (SNP) on chromosome 7p21.1 and large vessel ischaemic stroke, was recently identified. The most likely underlying gene is histone deacetylase 9 (HDAC9). The mechanism by which HDAC9 increases stroke risk is not clear; both vascular and neuronal mechanisms have been proposed. Methods We determined whether the lead SNPs were associated with asymptomatic carotid plaque (N=25179) and carotid intima-media thickness (N=31210) detected by carotid ultrasound in a meta-analysis of population based and community cohorts. Immunohistochemistry was used to determine whether HDAC9 was expressed in healthy human cerebral and systemic arteries. In the Tampere Vascular Study we determined whether HDAC9 mRNA expression was altered in carotid (N=29), abdominal aortic (N=15) and femoral (N=24) atherosclerotic plaques compared with control (left internal thoracic, N=28) arteries. Results Both SNPs (rs11984041 and rs2107595) were associated with common carotid IMT (rs2107595 p=0.0018) and with presence of carotid plaque (rs2107595 p=0.0022). In both cerebral and systemic arteries, HDAC9 labelling was seen in nuclei and cytoplasm of vascular smooth muscle cells, and in endothelial cells. HDAC9 expression was upregulated in carotid plaques compared to left internal thoracic controls (p=0.00000103). It was also up-regulated in aortic and femoral plaques compared to controls, with mRNA expression increased in carotid compared with femoral plaques (p=0.0038). Conclusions Our results are consistent with the 7p21.1 association acting via promoting atherosclerosis, and consistent with alterations in HDAC9 expression mediating this increased risk. Further studies in experimental models are required to confirm this link. PMID:23449258

Assessment of serum leptin, pregnancy-associated plasma protein A and CRP levels as indicators of plaque vulnerability in patients with acute coronary syndrome.

PubMed

Lodh, Moushumi; Goswami, Binita; Parida, Ashok; Patra, Surajeet; Saxena, Alpana

2012-07-01

A multifactorial aetiology of coronary artery disease (CAD) has been established in the recent past. Extensive research is now underway to understand the mechanisms responsible for plaque vulnerability. The identification of a novel biomarker that will help in the assessment of plaque status is urgently needed for the purpose of patient stratification and prognostication. The aim of the present study was to evaluate leptin, pregnancy-associated plasma protein A (PAPP-A) and C-reactive protein (CRP) levels in patients with acute coronary syndrome and to assess their diagnostic efficacy in the identification of vulnerable plaques. The study group comprised 105 patients who had chest pain along with ECG changes (ST elevation, ST depression, T inversion) and raised cardiac enzyme levels. Sixty-two patients with chest pain and ECG changes but with normal cardiac enzyme profiles were included in the control group. Lipid profiles, and leptin, PAPP-A and CRP levels were assessed in these two groups. Receiver operating characteristics (ROC) curves were plotted to determine the utility of the parameters under study as markers of plaque vulnerability. Significantly higher levels of serum lipoprotein (a), leptin, PAPP-A and high-sensitivity CRP (hs-CRP) were observed in the cases than in the controls. A positive correlation was observed between CRP and PAPP-A levels as well as CRP and leptin concentrations. ROC curve analysis revealed similar efficacies of CRP and PAPP-A levels in their ability to detect unstable plaques with areas under the curve of 0.762 and 0.732, respectively. Multivariate analysis established the superiority of hs-CRP as a predictor of plaque instability. Our study highlights the utility of both CRP and PAPP-A levels as determinants of plaque instability. Our findings necessitate population-based follow-up studies to establish the superiority of either of the two biomarkers in the field of preventive cardiology.

Fractal analysis of plaque border, a novel method for the quantification of atherosclerotic plaque contour irregularity, is associated with pro-atherogenic plasma lipid profile in subjects with non-obstructive carotid stenoses.

PubMed

Moroni, Francesco; Magnoni, Marco; Vergani, Vittoria; Ammirati, Enrico; Camici, Paolo G

2018-01-01

Plaque border irregularity is a known imaging characteristic of vulnerable plaques, but its evaluation heavily relies on subjective evaluation and operator expertise. Aim of the present work is to propose a novel fractal-analysis based method for the quantification of atherosclerotic plaque border irregularity and assess its relation with cardiovascular risk factors. Forty-two asymptomatic subjects with carotid stenosis underwent ultrasound evaluation and assessment of cardiovascular risk factors. Total, low-density lipoprotein (LDL), high-density lipoprotein (HDL) plasma cholesterol and triglycerides concentrations were measured for each subject. Fractal analysis was performed in all the carotid segments affected by atherosclerosis, i.e. 147 segments. The resulting fractal dimension (FD) is a measure of irregularity of plaque profile on long axis view of the plaque. FD in the severest stenosis (main plaque FD,mFD) was 1.136±0.039. Average FD per patient (global FD,gFD) was 1.145±0.039. FD was independent of other plaque characteristics. mFD significantly correlated with plasma HDL (r = -0.367,p = 0.02) and triglycerides-to-HDL ratio (r = 0.480,p = 0.002). Fractal analysis is a novel, readily available, reproducible and inexpensive technique for the quantitative measurement of plaque irregularity. The correlation between low HDL levels and plaque FD suggests a role for HDL in the acquisition of morphologic features of plaque instability. Further studies are needed to validate the prognostic value of fractal analysis in carotid plaques evaluation.

The influence of computational strategy on prediction of mechanical stress in carotid atherosclerotic plaques: comparison of 2D structure-only, 3D structure-only, one-way and fully coupled fluid-structure interaction analyses.

PubMed

Huang, Yuan; Teng, Zhongzhao; Sadat, Umar; Graves, Martin J; Bennett, Martin R; Gillard, Jonathan H

2014-04-11

Compositional and morphological features of carotid atherosclerotic plaques provide complementary information to luminal stenosis in predicting clinical presentations. However, they alone cannot predict cerebrovascular risk. Mechanical stress within the plaque induced by cyclical changes in blood pressure has potential to assess plaque vulnerability. Various modeling strategies have been employed to predict stress, including 2D and 3D structure-only, 3D one-way and fully coupled fluid-structure interaction (FSI) simulations. However, differences in stress predictions using different strategies have not been assessed. Maximum principal stress (Stress-P1) within 8 human carotid atherosclerotic plaques was calculated based on geometry reconstructed from in vivo computerized tomography and high resolution, multi-sequence magnetic resonance images. Stress-P1 within the diseased region predicted by 2D and 3D structure-only, and 3D one-way FSI simulations were compared to 3D fully coupled FSI analysis. Compared to 3D fully coupled FSI, 2D structure-only simulation significantly overestimated stress level (94.1 kPa [65.2, 117.3] vs. 85.5 kPa [64.4, 113.6]; median [inter-quartile range], p=0.0004). However, when slices around the bifurcation region were excluded, stresses predicted by 2D structure-only simulations showed a good correlation (R(2)=0.69) with values obtained from 3D fully coupled FSI analysis. 3D structure-only model produced a small yet statistically significant stress overestimation compared to 3D fully coupled FSI (86.8 kPa [66.3, 115.8] vs. 85.5 kPa [64.4, 113.6]; p<0.0001). In contrast, one-way FSI underestimated stress compared to 3D fully coupled FSI (78.8 kPa [61.1, 100.4] vs. 85.5 kPa [64.4, 113.7]; p<0.0001). A 3D structure-only model seems to be a computationally inexpensive yet reasonably accurate approximation for stress within carotid atherosclerotic plaques with mild to moderate luminal stenosis as compared to fully coupled FSI analysis. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Fish consumption, fish oil supplements and risk of atherosclerosis in the Tromsø study.

PubMed

Johnsen, Stein Harald; Jacobsen, Bjarne K; Brækkan, Sigrid K; Hansen, John-Bjarne; Mathiesen, Ellisiv B

2018-05-25

Whether long-chain n-3 PUFAs of marine origin have an anti-atherogenic effect in the general population has hardly been studied. In this population-based study, we hypothesized that fatty fish and fish oil intake protect against development of novel atherosclerotic plaques and is associated with reduced plaque size. We obtained questionnaire-based information on fish consumption and carotid ultrasonography from 3900 persons aged 45-74 years. The questionnaires were validated by measuring serum concentrations of PUFAs and triglycerides in a subgroup. At follow-up seven years later, 2983 (76%) went through a second ultrasound scanning. Logistic regression and general linear models were used to analyze the outcome (plaque presence and plaque area) as a function of fish consumption, including analyses stratified on fish oil supplements. At baseline, lean fish intake < 1 time/week vs. 1-1.9 times/week was associated with risk of plaque (OR 1.34, 95% CI 1.03-1.76). Fatty fish intake and use of fish oil supplements were not statistically significantly associated with atherosclerosis at baseline. In persons without plaque at baseline, total fish consumption ≥3 times/week vs. 1-1.9 times/week was associated with risk of novel plaque (OR 1.32, 95% CI 1.01-1.73) and larger plaque area (1.76 mm 2 vs. 1.46 mm 2 , p = 0.02) at follow-up. Adjustments for use of fish oil supplements had no impact on the associations, and no interactions were seen between total, fatty or lean fish consumption and fish oil intake. We found no protective effect of fatty fish eating or fish oil supplements on atherosclerotic plaque formation or plaque area in a general population. Lean fish consumption was associated with a reduced risk for plaque in cross-sectional analysis, suggesting that the beneficial effects of fish consumption on atherosclerosis may be mediated through other mechanisms than n-3 PUFAs.

Comparison between a new computer program and the reference software for gray-scale median analysis of atherosclerotic carotid plaques.

PubMed

Casella, Ivan Benaduce; Fukushima, Rodrigo Bono; Marques, Anita Battistini de Azevedo; Cury, Marcus Vinícius Martins; Presti, Calógero

2015-03-01

To compare a new dedicated software program and Adobe Photoshop for gray-scale median (GSM) analysis of B-mode images of carotid plaques. A series of 42 carotid plaques generating ≥50% diameter stenosis was evaluated by a single observer. The best segment for visualization of internal carotid artery plaque was identified on a single longitudinal view and images were recorded in JPEG format. Plaque analysis was performed by both programs. After normalization of image intensity (blood = 0, adventitial layer = 190), histograms were obtained after manual delineation of plaque. Results were compared with nonparametric Wilcoxon signed rank test and Kendall tau-b correlation analysis. GSM ranged from 00 to 100 with Adobe Photoshop and from 00 to 96 with IMTPC, with a high grade of similarity between image pairs, and a highly significant correlation (R = 0.94, p < .0001). IMTPC software appears suitable for the GSM analysis of carotid plaques. © 2014 Wiley Periodicals, Inc.

Gene transfer of inducible nitric oxide synthase complementary DNA regresses the fibrotic plaque in an animal model of Peyronie's disease.

PubMed

Davila, Hugo H; Magee, Thomas R; Vernet, Dolores; Rajfer, Jacob; Gonzalez-Cadavid, Nestor F

2004-11-01

The goal of the present study was to investigate the antifibrotic role of inducible nitric oxide synthase (iNOS) in Peyronie's disease (PD) by determining whether a plasmid expressing iNOS (piNOS) injected into a PD-like plaque can induce regression of the plaque. A PD-like plaque was induced with fibrin in the penile tunica albuginea of mice and then injected with a luciferase-expressing plasmid (pLuc), either alone or with piNOS, following luciferase expression in vivo by bioluminescence imaging. Rats were treated with either piNOS, an empty control plasmid (pC), or saline. Other groups were treated with pC or piNOS, in the absence of fibrin. Tissue sections were stained for collagen, transforming growth factor (TGF) beta1, and plasminogen-activator inhibitor (PAI-1) as profibrotic factors; copper-zinc superoxide dismutase (CuZn SOD) as scavenger of reactive oxygen species (ROS); and nitrotyrosine to detect nitric oxide reaction with ROS. Quantitative image analysis was applied. Both iNOS and xanthine oxido-reductase (XOR; oxidative stress) were estimated by Western blot analysis. Luciferase reporter expression was restricted to the penis, peaked at 3 days after injection, but continued for at least 3 wk. In rats receiving piNOS, iNOS expression also peaked at 3 days, but expression decreased at the end of treatment, when a considerable reduction of plaque size occurred. Protein nitrotyrosine, XOR, and CuZn SOD increased, and TGFbeta1 and PAI-1 decreased. The piNOS gene transfer regressed the PD plaque and expression of profibrotic factors, supporting the view that endogenous iNOS induction in PD is defense mechanism by the tissue against fibrosis.

Frequency of Subclinical Atherosclerosis in Brazilian HIV-Infected Patients.

PubMed

Salmazo, Péricles Sidnei; Bazan, Silméia Garcia Zanati; Shiraishi, Flávio Gobbis; Bazan, Rodrigo; Okoshi, Katashi; Hueb, João Carlos

2018-04-09

AIDS as well as atherosclerosis are important public health problems. The longer survival among HIV-infected is associated with increased number of cardiovascular events in this population, and this association is not fully understood. To identify the frequency of subclinical atherosclerosis in HIV-infected patients compared to control subjects; to analyze associations between atherosclerosis and clinical and laboratory variables, cardiovascular risk factors, and the Framingham coronary heart disease risk score (FCRS). Prospective cross-sectional case-control study assessing the presence of subclinical atherosclerosis in 264 HIV-infected patients and 279 controls. Clinical evaluation included ultrasound examination of the carotid arteries, arterial stiffness by pulse wave velocity (PWV) and augmentation index (AIx), laboratory analysis of peripheral blood, and cardiovascular risk according to FCRS criteria. The significance level adopted in the statistical analysis was p < 0.05. Plaques were found in 37% of the HIV group and 4% of controls (p < 0.001). Furthermore, carotid intima-media thickness was higher in the HIV group than in controls (p < 0.001). Patients with carotid plaque had higher fasting glucose, total cholesterol, low-density lipoprotein cholesterol, and triglycerides than those without plaques. The presence of HIV, adjusted for age, overweight/obesity, and smoking increased by almost fivefold the risk of atherosclerotic carotid plaque (OR: 4.9; 95%CI: 2.5-9.9; p < 0.001). Exposure to protease inhibitors did not influence carotid intima-media thickness, was not associated with carotid plaque frequency, and did not alter the mechanical characteristics of the arterial system (PWV and AIx). HIV-infected patients are at increased risk of atherosclerosis in association with classical cardiovascular risk factors. Treatment with protease inhibitors does not promote functional changes in the arteries, and shows no association with increased frequency of atherosclerotic plaques in carotid arteries. The FCRS may be inappropriate for this population.

A comparison between plaque-based and vessel-based measurement for plaque component using volumetric intravascular ultrasound radiofrequency data analysis.

PubMed

Shin, Eun-Seok; Garcia-Garcia, Hector M; Garg, Scot; Serruys, Patrick W

2011-04-01

Although percent plaque components on plaque-based measurement have been used traditionally in previous studies, the impact of vessel-based measurement for percent plaque components have yet to be studied. The purpose of this study was therefore to correlate percent plaque components derived by plaque- and vessel-based measurement using intravascular ultrasound virtual histology (IVUS-VH). The patient cohort comprised of 206 patients with de novo coronary artery lesions who were imaged with IVUS-VH. Age ranged from 35 to 88 years old, and 124 patients were male. Whole pullback analysis was used to calculate plaque volume, vessel volume, and absolute and percent volumes of fibrous, fibrofatty, necrotic core, and dense calcium. The plaque and vessel volumes were well correlated (r = 0.893, P < 0.001). There was a strong correlation between percent plaque components volumes calculated by plaque and those calculated by vessel volumes (fibrous; r = 0.927, P < 0.001, fibrofatty; r = 0.972, P < 0.001, necrotic core; r = 0.964, P < 0.001, dense calcium; r = 0.980, P < 0.001,). Plaque and vessel volumes correlated well to the overall plaque burden. For percent plaque component volume, plaque-based measurement was also highly correlated with vessel-based measurement. Therefore, the percent plaque component volume calculated by vessel volume could be used instead of the conventional percent plaque component volume calculated by plaque volume.

A method for the quantitative site-specific study of the biochemistry within dental plaque biofilms formed in vivo.

PubMed

Robinson, C; Kirkham, J; Percival, R; Shore, R C; Bonass, W A; Brookes, S J; Kusa, L; Nakagaki, H; Kato, K; Nattress, B

1997-01-01

The study of plaque biofilms in the oral cavity is difficult as plaque removal inevitably disrupts biofilm integrity precluding kinetic studies involving the penetration of components and metabolism of substrates in situ. A method is described here in which plaque is formed in vivo under normal (or experimental) conditions using a collection device which can be removed from the mouth after a specified time without physical disturbance to the plaque biofilm, permitting site-specific analysis or exposure of the undisturbed plaque to experimental conditions in vitro. Microbiological analysis revealed plaque flora which was similar to that reported from many natural sources. Analytical data can be related to plaque volume rather than weight. Using this device, plaque fluoride concentrations have been shown to vary with plaque depth and in vitro short-term exposure to radiolabelled components may be carried out, permitting important conclusions to be drawn regarding the site-specific composition and dynamics of dental plaque.

Recolonization of the oral cavity by Streptococcus mutans after a combined mechanical/chemical antisepsis protocol.

PubMed

Farina, R; Squarzoni, M A; Calura, G; Trombelli, L

2009-06-01

The bacterial colonization of teeth by Streptococcus mutans (StrepM) represents a major risk factor for the development of dental caries. At present, no clinical studies have explored the effect of a combined mechanical-chemical antisepsis protocol in a periodontally-healthy population and the pattern of recolonization of StrepM in subjects whose StrepM infection was successfully eradicated. The present study was designed in order to 1) determine the salivary and plaque changes in StrepM content after a combined mechanical/chemical antisepsis protocol; and 2) evaluate the pattern of recolonization when StrepM was successfully eradicated from saliva and plaque. Thirty-five periodontally-healthy and caries-susceptible subjects successfully entered and concluded the study. At baseline, non-surgical periodontal therapy was performed according to the principles of full mouth disinfection. Adjunctive home-based rinsing with a 0.2% chlorhexidine mouthrinse was requested for the following week. StrepM concentration was assessed in saliva and plaque at the initial contact appointment, at baseline, and 1-week, 1-month, 3-month and 6-month follow-up. A significant effect of ''time'' on StrepM concentration in saliva and plaque was observed (P<0.000). In subjects with successful eradication of StrepM at 1 week (N=17 plaque samples), StrepM infection recurrence occurred within 3-6 months. The results of the present study demonstrated that 1) the application of the investigated mechanical/chemical antisepsis protocol can effectively reduce StrepM colonies in saliva and plaque of periodontally healthy subjects; and 2) in plaque samples, StrepM infection recurrence tends to occur within 3-6 months.

Efficacy of 3 toothbrush treatments on plaque removal in orthodontic patients assessed with digital plaque imaging: a randomized controlled trial.

PubMed

Erbe, Christina; Klukowska, Malgorzata; Tsaknaki, Iris; Timm, Hans; Grender, Julie; Wehrbein, Heinrich

2013-06-01

Good oral hygiene is a challenge for orthodontic patients because food readily becomes trapped around the brackets and under the archwires, and appliances are an obstruction to mechanical brushing. The purpose of this study was to compare plaque removal efficacy of 3 toothbrush treatments in orthodontic subjects. This was a replicate-use, single-brushing, 3-treatment, examiner-blind, randomized, 6-period crossover study with washout periods of approximately 24 hours between visits. Forty-six adolescent and young adult patients with fixed orthodontics from a university clinic in Germany were randomized, based on computer-generated randomization, to 1 of 3 treatments: (1) oscillating-rotating electric toothbrush with a specially designed orthodontic brush head (Oral-B Triumph, OD17; Procter & Gamble, Cincinnati, Ohio); (2) the same electric toothbrush handle with a regular brush head (EB25; Procter & Gamble); and (3) a regular manual toothbrush (American Dental Association, Chicago, Ill). The primary outcome was the plaque score change from baseline, which we determined using digital plaque image analysis. Forty-five subjects completed the study. The differences in mean plaque removal (95% confidence interval) between the electric toothbrush with an orthodontic brush head (6% [4.4%-7.6%]) or a regular brush head (3.8% [2.2%-5.3%]) and the manual toothbrush were significant (P <0.001). Plaque removal with the electric toothbrush with the orthodontic brush head was superior (2.2%; P = 0.007) to the regular brush head. No adverse events were seen. The electric toothbrush, with either brush head, demonstrated significantly greater plaque removal over the manual brush. The orthodontic brush head was superior to the regular head. Copyright © 2013 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

Atherosclerotic plaque characterization by spatial and temporal speckle pattern analysis

NASA Astrophysics Data System (ADS)

Tearney, Guillermo J.; Bouma, Brett E.

2002-04-01

Improved methods are needed to identify the vulnerable coronary plaques responsible for acute myocardial infraction or sudden cardiac death. We describe a method for characterizing the structure and biomechanical properties of atherosclerotic plaques based on speckle pattern fluctuations. Near-field speckle images were acquired from five human aortic specimens ex vivo. The speckle decorrelation time constant varied significantly for vulnerable aortic plaques (τ = 40 ms) versus stable plaques (τ = 400 ms) and normal aorta (τ = 500 ms). These initial results indicate that different atherosclerotic plaque types may be distinguished by analysis of temporal and spatial speckle pattern fluctuations.

ARC-2006-ACD06-0213-011

NASA Image and Video Library

2006-10-03

Ames and Moffett Field (MFA) historical sites and memorials Unitary Plan Wind Tunned plaza; display and historical site plaques with the NASA logo on the Wind Tunnel valve as a backdrop. shown is the Unitary International Historic Mechanical Engineering Landmark Dedication plaque (American Society of Mechanical Engineers) May 5, 1995

Targeted Near-Infrared Fluorescence Imaging of Atherosclerosis: Clinical and Intracoronary Evaluation of Indocyanine Green.

PubMed

Verjans, Johan W; Osborn, Eric A; Ughi, Giovanni J; Calfon Press, Marcella A; Hamidi, Ehsan; Antoniadis, Antonios P; Papafaklis, Michail I; Conrad, Mark F; Libby, Peter; Stone, Peter H; Cambria, Richard P; Tearney, Guillermo J; Jaffer, Farouc A

2016-09-01

This study sought to determine whether indocyanine green (ICG)-enhanced near-infrared fluorescence (NIRF) imaging can illuminate high-risk histologic plaque features of human carotid atherosclerosis, and in coronary atheroma of living swine, using intravascular NIRF-optical coherence tomography (OCT) imaging. New translatable imaging approaches are needed to identify high-risk biological signatures of atheroma. ICG is a U.S. Food and Drug Administration-approved NIRF imaging agent that experimentally targets plaque macrophages and lipid in areas of enhanced endothelial permeability. However, it is unknown whether ICG can target atheroma in patients. Eight patients were enrolled in the BRIGHT-CEA (Indocyanine Green Fluorescence Uptake in Human Carotid Artery Plaque) trial. Five patients were injected intravenously with ICG 99 ± 25 min before clinically indicated carotid endarterectomy. Three saline-injected endarterectomy patients served as control subjects. Excised plaques underwent analysis by intravascular NIRF-OCT, reflectance imaging, microscopy, and histopathology. Next, following ICG intravenous injection, in vivo intracoronary NIRF-OCT and intravascular ultrasound imaged 3 atheroma-bearing coronary arteries of a diabetic, cholesterol-fed swine. ICG was well tolerated; no adverse clinical events occurred up to 30 days post-injection. Multimodal NIRF imaging including intravascular NIRF-OCT revealed that ICG accumulated in all endarterectomy specimens. Plaques from saline-injected control patients exhibited minimal NIRF signal. In the swine experiment, intracoronary NIRF-OCT identified ICG uptake in all intravascular ultrasound-identified plaques in vivo. On detailed microscopic evaluation, ICG localized to plaque areas exhibiting impaired endothelial integrity, including disrupted fibrous caps, and within areas of neovascularization. Within human plaque areas of endothelial abnormality, ICG was spatially related to localized zones of plaque macrophages and lipid, and, notably, intraplaque hemorrhage. This study demonstrates that ICG targets human plaques exhibiting endothelial abnormalities and provides new insights into its targeting mechanisms in clinical and experimental atheroma. Intracoronary NIRF-OCT of ICG may offer a novel, clinically translatable approach to image pathobiological aspects of coronary atherosclerosis. (Indocyanine Green Fluorescence Uptake in Human Carotid Artery Plaque [BRIGHT-CEA]; NCT01873716). Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Intravascular laser speckle imaging for the mechanical analysis of coronary plaques (Conference Presentation)

NASA Astrophysics Data System (ADS)

Hosoda, Masaki; Wang, Jing; Tsikudi, Diane; Nadkarni, Seemantini

2016-02-01

Acute myocardial infarction is frequently caused by the rupture of coronary plaques with severely compromised viscoelastic properties. We have developed a new optical technology termed intravascular laser speckle imaging (ILSI) that evaluates plaque viscoelastic properties, by measuring the time scale (time constant, τ) of temporally evolving laser speckle fluctuations. To enable coronary evaluation in vivo, an optical ILSI catheter has been developed that accomplishes omni-directional illumination and viewing of the entire coronary circumference without the need for mechanical rotation. Here, we describe the capability of ILSI for evaluating human coronary atherosclerosis in cadaveric hearts. ILSI was conducted in conjunction with optical coherence tomography (OCT) imaging in five human cadaveric hearts. The left coronary artery (LCA), left anterior descending (LAD), left circumflex artery (LCx), and right coronary artery (RCA) segments were resected and secured on custom-developed coronary holders to enable accurate co-registration between ILSI, OCT, and histopathology. Speckle time constants, τ, calculated from each ILSI section were compared with lipid and collagen content measured from quantitative Histopathological analysis of the corresponding Oil Red O and Picrosirius Red stained sections. Because the presence of low viscosity lipid elicits rapid speckle fluctuations, we observed an inverse correlation between τ measured by ILSI and lipid content (R= -0.64, p< 0.05). In contrast, the higher viscoelastic modulus of fibrous regions resulted in a positive correlation between τ and collagen content (R= 0.54, p< 0.05). These results demonstrate the feasibility of conducting ILSI evaluation of arterial mechanical properties using a miniaturized omni-directional catheter.

Preintervention lesion remodelling affects operative mechanisms of balloon optimised directional coronary atherectomy procedures: a volumetric study with three dimensional intravascular ultrasound

PubMed Central

von Birgelen, C; Mintz, G; de Vrey, E A; Serruys, P; Kimura, T; Nobuyoshi, M; Popma, J; Leon, M; Erbel, R; de Feyter, P J

2000-01-01

AIMS—To classify atherosclerotic coronary lesions on the basis of adequate or inadequate compensatory vascular enlargement, and to examine changes in lumen, plaque, and vessel volumes during balloon optimised directional coronary atherectomy procedures in relation to the state of adaptive remodelling before the intervention.
DESIGN—29 lesion segments in 29 patients were examined with intravascular ultrasound before and after successful balloon optimised directional coronary atherectomy procedures, and a validated volumetric intravascular ultrasound analysis was performed off-line to assess the atherosclerotic lesion remodelling and changes in plaque and vessel volumes that occurred during the intervention. Based on the intravascular ultrasound data, lesions were classified according to whether there was inadequate (group I) or adequate (group II) compensatory enlargement.
RESULTS—There was no significant difference in patient and lesion characteristics between groups I and II (n = 10 and 19), including lesion length and details of the intervention. Quantitative coronary angiographic data were similar for both groups. However, plaque and vessel volumes were significantly smaller in group I than in II. In group I, 9 (4)% (mean (SD)) of the plaque volume was ablated, while in group II 16 (11)% was ablated (p = 0.01). This difference was reflected in a lower lumen volume gain in group I than in group II (46 (18) mm3 v 80 (49) mm3 (p < 0.02)).
CONCLUSIONS—Preintervention lesion remodelling has an impact on the operative mechanisms of balloon optimised directional coronary atherectomy procedures. Plaque ablation was found to be particularly low in lesions with inadequate compensatory vascular enlargement.


Keywords: intravascular ultrasound; ultrasonics; remodelling; coronary artery disease; atherectomy PMID:10648496

In Vivo Visualization of Alzheimer’s Amyloid Plaques by MRI in Transgenic Mice Without a Contrast Agent

PubMed Central

Jack, Clifford R.; Garwood, Michael; Wengenack, Thomas M.; Borowski, Bret; Curran, Geoffrey L.; Lin, Joseph; Adriany, Gregor; Grohn, Olli H.J.; Grimm, Roger; Poduslo, Joseph F.

2009-01-01

One of the cardinal pathologic features of Alzheimer’s disease (AD) is formation of senile, or amyloid, plaques. Transgenic mice have been developed that express one or more of the genes responsible for familial AD in humans. Doubly transgenic mice develop “human-like” plaques, providing a mechanism to study amyloid plaque biology in a controlled manner. Imaging of labeled plaques has been accomplished with other modalities, but only MRI has sufficient spatial and contrast resolution to visualize individual plaques non-invasively. Methods to optimize visualization of plaques in vivo in transgenic mice at 9.4 T using a spin echo sequence based on adiabatic pulses are described. Preliminary results indicate that a spin echo acquisition more accurately reflects plaque size, while a T2* weighted gradient echo sequence reflects plaque iron content not plaque size. In vivo MRI – ex vivo MRI – in vitro histological correlations are provided. Histologically verified plaques as small as 50 μm in diameter were visualized in the living animal. To our knowledge this work represents the first demonstration of non-invasive in vivo visualization of individual AD plaques without the use of a contrast agent. PMID:15562496

[Study on the effect of rhizoma Chuanxiong, radix paeoniae rubra and the compound of their active ingredients, Xiongshao Capsule, on stability of atherosclerotic plaque in ApoE(-/-) mice].

PubMed

Xu, Hao; Wen, Chuan; Chen, Ke-Ji

2007-06-01

To observe the effect of Rhizoma chuanxiong (RC), Radix Paeoniae rubra (RP) and Xiongshao Capsule (XC, a compound of their active ingredients, Chuanxingols and Paeoniflorins) on stability of atherosclerotic plaque in ApoE-/- mice and to explore the probable mechanisms. The effect of RC, RP and XC in stabilizing atherosclerotic plaque, in terms of pathologic morphology, cell composition and inflammatory reaction, in the atherosclerosis model established on ApoE-/- mice was studied by using optical microscope, immunohistochemical method and computerized imaging analysis respectively. After the ApoE-/- mice being fed with high fat diet for 26 weeks, obvious atherosclerotic lesion with typical unstable characteristics was found in their aortic root. Both RC and RP had certain effects in lowering total cholesterol and increasing the thickness of fibre cap. RC could also lower the serum triglyceride (TC) level and the lipid-core/plaque area ratio as well as reduce the macrocytic infiltration. In addition to the same effects as above mentioned, XS could also raise the levels of high density lipoprotein-cholesterol (HDL-C), lower TC/HDL-C ratio, reduce inflammatory reaction and enlarge the collagen area in plaque. The acting links of RC and RP on atherosclerosis are different, the compound of their active ingredients, XS, shows a more evident effect in intervening unstable plaque. It demonstrates the effect-enhancing power of TCM compound and is worth further studying.

Mechanisms of erosion of atherosclerotic plaques.

PubMed

Quillard, Thibaut; Franck, Grégory; Mawson, Thomas; Folco, Eduardo; Libby, Peter

2017-10-01

The present review explores the mechanisms of superficial intimal erosion, a common cause of thrombotic complications of atherosclerosis. Human coronary artery atheroma that give rise to thrombosis because of erosion differ diametrically from those associated with fibrous cap rupture. Eroded lesions characteristically contain few inflammatory cells, abundant extracellular matrix, and neutrophil extracellular traps (NETs). Innate immune mechanisms such as engagement of Toll-like receptor 2 (TLR2) on cultured endothelial cells can impair their viability, attachment, and ability to recover a wound. Hyaluronan fragments may serve as endogenous TLR2 ligands. Mouse experiments demonstrate that flow disturbance in arteries with neointimas tailored to resemble features of human eroded plaques disturbs endothelial cell barrier function, impairs endothelial cell viability, recruits neutrophils, and provokes endothelial cells desquamation, NET formation, and thrombosis in a TLR2-dependent manner. Mechanisms of erosion have received much less attention than those that provoke plaque rupture. Intensive statin treatment changes the characteristic of plaques that render them less susceptible to rupture. Thus, erosion may contribute importantly to the current residual burden of risk. Understanding the mechanisms of erosion may inform the development and deployment of novel therapies to combat the remaining atherothrombotic risk in the statin era.

Diagnosis of vulnerable atherosclerotic plaques by time-resolved fluorescence spectroscopy and ultrasound imaging.

PubMed

Jo, J A; Fang, Q; Papaioannou, T; Qiao, J H; Fishbein, M C; Beseth, B; Dorafshar, A H; Reil, T; Baker, D; Freischlag, J; Shung, K K; Sun, L; Marcu, L

2006-01-01

In this study, time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) and ultrasonography were applied to detect vulnerable (high-risk) atherosclerotic plaque. A total of 813 TR-LIFS measurements were taken from carotid plaques of 65 patients, and subsequently analyzed using the Laguerre deconvolution technique. The investigated spots were classified by histopathology as thin, fibrotic, calcified, low-inflamed, inflamed and necrotic lesions. Spectral and time-resolved parameters (normalized intensity values and Laguerre expansion coefficients) were extracted from the TR-LIFS data. Feature selection for classification was performed by either analysis of variance (ANOVA) or principal component analysis (PCA). A stepwise linear discriminant analysis algorithm was developed for detecting inflamed and necrotic lesion, representing the most vulnerable plaques. These vulnerable plaques were detected with high sensitivity (>80%) and specificity (>90%). Ultrasound (US) imaging was obtained in 4 carotid plaques in addition to TR-LIFS examination. Preliminary results indicate that US provides important structural information of the plaques that could be combined with the compositional information obtained by TR-LIFS, to obtain a more accurate diagnosis of vulnerable atherosclerotic plaque.

The simulation of magnetic resonance elastography through atherosclerosis.

PubMed

Thomas-Seale, L E J; Hollis, L; Klatt, D; Sack, I; Roberts, N; Pankaj, P; Hoskins, P R

2016-06-14

The clinical diagnosis of atherosclerosis via the measurement of stenosis size is widely acknowledged as an imperfect criterion. The vulnerability of an atherosclerotic plaque to rupture is associated with its mechanical properties. The potential to image these mechanical properties using magnetic resonance elastography (MRE) was investigated through synthetic datasets. An image of the steady state wave propagation, equivalent to the first harmonic, can be extracted directly from finite element analysis. Inversion of this displacement data yields a map of the shear modulus, known as an elastogram. The variation of plaque composition, stenosis size, Gaussian noise, filter thresholds and excitation frequency were explored. A decreasing mean shear modulus with an increasing lipid composition was identified through all stenosis sizes. However the inversion algorithm showed sensitivity to parameter variation leading to artefacts which disrupted both the elastograms and quantitative trends. As noise was increased up to a realistic level, the contrast was maintained between the fully fibrous and lipid plaques but lost between the interim compositions. Although incorporating a Butterworth filter improved the performance of the algorithm, restrictive filter thresholds resulted in a reduction of the sensitivity of the algorithm to composition and noise variation. Increasing the excitation frequency improved the techniques ability to image the magnitude of the shear modulus and identify a contrast between compositions. In conclusion, whilst the technique has the potential to image the shear modulus of atherosclerotic plaques, future research will require the integration of a heterogeneous inversion algorithm. Copyright © 2016 Elsevier Ltd. All rights reserved.

CT coronary angiography: impact of adapted statistical iterative reconstruction (ASIR) on coronary stenosis and plaque composition analysis.

PubMed

Fuchs, Tobias A; Fiechter, Michael; Gebhard, Cathérine; Stehli, Julia; Ghadri, Jelena R; Kazakauskaite, Egle; Herzog, Bernhard A; Husmann, Lars; Gaemperli, Oliver; Kaufmann, Philipp A

2013-03-01

To assess the impact of adaptive statistical iterative reconstruction (ASIR) on coronary plaque volume and composition analysis as well as on stenosis quantification in high definition coronary computed tomography angiography (CCTA). We included 50 plaques in 29 consecutive patients who were referred for the assessment of known or suspected coronary artery disease (CAD) with contrast-enhanced CCTA on a 64-slice high definition CT scanner (Discovery HD 750, GE Healthcare). CCTA scans were reconstructed with standard filtered back projection (FBP) with no ASIR (0 %) or with increasing contributions of ASIR, i.e. 20, 40, 60, 80 and 100 % (no FBP). Plaque analysis (volume, components and stenosis degree) was performed using a previously validated automated software. Mean values for minimal diameter and minimal area as well as degree of stenosis did not change significantly using different ASIR reconstructions. There was virtually no impact of reconstruction algorithms on mean plaque volume or plaque composition (e.g. soft, intermediate and calcified component). However, with increasing ASIR contribution, the percentage of plaque volume component between 401 and 500 HU decreased significantly (p < 0.05). Modern image reconstruction algorithms such as ASIR, which has been developed for noise reduction in latest high resolution CCTA scans, can be used reliably without interfering with the plaque analysis and stenosis severity assessment.

A novel workflow combining plaque imaging, plaque and plasma proteomics identifies biomarkers of human coronary atherosclerotic plaque disruption.

PubMed

Lee, Regent; Fischer, Roman; Charles, Philip D; Adlam, David; Valli, Alessandro; Di Gleria, Katalin; Kharbanda, Rajesh K; Choudhury, Robin P; Antoniades, Charalambos; Kessler, Benedikt M; Channon, Keith M

2017-01-01

Atherosclerotic plaque rupture is the culprit event which underpins most acute vascular syndromes such as acute myocardial infarction. Novel biomarkers of plaque rupture could improve biological understanding and clinical management of patients presenting with possible acute vascular syndromes but such biomarker(s) remain elusive. Investigation of biomarkers in the context of de novo plaque rupture in humans is confounded by the inability to attribute the plaque rupture as the source of biomarker release, as plaque ruptures are typically associated with prompt down-stream events of myocardial necrosis and systemic inflammation. We developed a novel approach to identify potential biomarkers of plaque rupture by integrating plaque imaging, using optical coherence tomography, with both plaque and plasma proteomic analysis in a human model of angioplasty-induced plaque disruption. We compared two pairs of coronary plaque debris, captured by a FilterWire Device, and their corresponding control samples and found matrix metalloproteinase 9 (MMP9) to be significantly enriched in plaque. Plaque contents, as defined by optical coherence tomography, affect the systemic changes of MMP9. Disruption of lipid-rich plaque led to prompt elevation of plasma MMP9, whereas disruption of non-lipid-rich plaque resulted in delayed elevation of plasma MMP9. Systemic MMP9 elevation is independent of the associated myocardial necrosis and systemic inflammation (measured by Troponin I and C-reactive protein, respectively). This information guided the selection of a subset of subjects of for further label free proteomics analysis by liquid chromatography tandem mass spectrometry (LC-MS/MS). We discovered five novel, plaque-enriched proteins (lipopolysaccharide binding protein, Annexin A5, eukaryotic translocation initiation factor, syntaxin 11, cytochrome B5 reductase 3) to be significantly elevated in systemic circulation at 5 min after plaque disruption. This novel approach for biomarker discovery in human coronary artery plaque disruption can identify new biomarkers related to human coronary artery plaque composition and disruption.

Temporal shifts in clinical presentation and underlying mechanisms of atherosclerotic disease.

PubMed

Pasterkamp, Gerard; den Ruijter, Hester M; Libby, Peter

2017-01-01

The concept of the 'vulnerable plaque' originated from pathological observations in patients who died from acute coronary syndrome. This recognition spawned a generation of research that led to greater understanding of how complicated atherosclerotic plaques form and precipitate thrombotic events. In current practice, an increasing number of patients who survive their first event present with non-ST-segment elevation myocardial infarction (NSTEMI) rather than myocardial infarction (MI) with ST-segment elevation (STEMI). The culprit lesions that provide the pathological substrate for NSTEMI can vary considerably from the so-called 'vulnerable plaque'. The shift in clinical presentation of MI and stroke corresponds temporally to a progressive change in the characteristics of human plaques away from the supposed characteristics of vulnerability. These alterations in the structure and function of human atherosclerotic lesions might mirror the modifications that are produced in experimental plaques by lipid lowering, inspired by the vulnerable plaque construct. The shift in the clinical presentations of the acute coronary syndromes mandates a critical reassessment of the underlying mechanisms, proposed risk scores, the results and interpretation of preclinical experiments, as well as recognition of the limitations of the use of population data and samples collected before the application of current preventive interventions.

Collagen and related extracellular matrix proteins in atherosclerotic plaque development.

PubMed

Shami, Annelie; Gonçalves, Isabel; Hultgårdh-Nilsson, Anna

2014-10-01

The structure, composition and turnover of the extracellular matrix (ECM) as well as cell-matrix interactions are crucial in the developing atherosclerotic plaque. There is a need for further insight into specific proteins in the ECM and their functions in the developing plaque, and during the last few years a number of publications have highlighted this very important field of research. These novel findings will be addressed in the present review. This review covers literature focused on collagen and ECM proteins interacting with collagen, and what their roles may be in plaque development. Acute myocardial infarction and stroke are common diseases that cause disability and mortality, and the underlying mechanism is often the rupture of a vulnerable atherosclerotic plaque. The vascular ECM and the tissue repair in the atherosclerotic lesion are important players in plaque progression. Understanding how specific proteins in the ECM interact with cells in the plaque and affect the fate of the plaque can lead to new treatments for cardiovascular disease.

Bone marrow endothelial progenitors in atherosclerotic plaque resolution

PubMed Central

Yao, Longbiao; Heuser-Baker, Janet; Herlea-Pana, Oana; Barlic-Dicen, Jana

2013-01-01

Atherosclerosis is a major cause of morbidity and mortality in the United States. Persistently elevated circulating low-density lipoprotein, or hypercholesterolemia, and deposition of low-density lipoprotein in the vascular wall are the main inducers of atherosclerosis, which manifests itself as arterial lesions or plaques. Some plaques become thrombosis-prone and rupture, causing acute myocardial infarction or stroke. Lowering plasma cholesterol through the use of statins is the primary intervention against atherosclerosis. Treatment with statins slows progression of atherosclerosis but can only support limited plaque regression. Partially regressed plaques continue to pose a serious threat due to their remaining potential to rupture. Thus, new interventions inducing complete reversal of atherosclerosis are being sought. Implementation of new therapies will require clear understanding of the mechanisms driving plaque resolution. In this Commentary, we highlight the role of bone marrow endothelial progenitors in atherosclerotic plaque regression and discuss how regenerative cell-based interventions could be used in combination with plasma lipid-lowering to induce plaque reversal in order to prevent and/or reduce adverse cardiovascular events. PMID:23538778

Multi-scale AM-FM motion analysis of ultrasound videos of carotid artery plaques

NASA Astrophysics Data System (ADS)

Murillo, Sergio; Murray, Victor; Loizou, C. P.; Pattichis, C. S.; Pattichis, Marios; Barriga, E. Simon

2012-03-01

An estimated 82 million American adults have one or more type of cardiovascular diseases (CVD). CVD is the leading cause of death (1 of every 3 deaths) in the United States. When considered separately from other CVDs, stroke ranks third among all causes of death behind diseases of the heart and cancer. Stroke accounts for 1 out of every 18 deaths and is the leading cause of serious long-term disability in the United States. Motion estimation of ultrasound videos (US) of carotid artery (CA) plaques provides important information regarding plaque deformation that should be considered for distinguishing between symptomatic and asymptomatic plaques. In this paper, we present the development of verifiable methods for the estimation of plaque motion. Our methodology is tested on a set of 34 (5 symptomatic and 29 asymptomatic) ultrasound videos of carotid artery plaques. Plaque and wall motion analysis provides information about plaque instability and is used in an attempt to differentiate between symptomatic and asymptomatic cases. The final goal for motion estimation and analysis is to identify pathological conditions that can be detected from motion changes due to changes in tissue stiffness.

Randomized Trial of Plaque-Identifying Toothpaste: Decreasing Plaque and Inflammation.

PubMed

Fasula, Kim; Evans, Carla A; Boyd, Linda; Giblin, Lori; Belavsky, Benjamin Z; Hetzel, Scott; McBride, Patrick; DeMets, David L; Hennekens, Charles H

2017-06-01

Randomized data are sparse about whether a plaque-identifying toothpaste reduces dental plaque and nonexistent for inflammation. Inflammation is intimately involved in the pathogenesis of atherosclerosis and is accurately measured by high-sensitivity C-reactive protein (hs-CRP), a sensitive marker for cardiovascular disease. The hypotheses that Plaque HD (TJA Health LLC, Joliet, Ill), a plaque-identifying toothpaste, produces statistically significant reductions in dental plaque and hs-CRP were tested in this randomized trial. Sixty-one apparently healthy subjects aged 19 to 44 years were assigned at random to this plaque-identifying (n = 31) or placebo toothpaste (n = 30) for 60 days. Changes from baseline to follow-up in dental plaque and hs-CRP were assessed. In an intention-to-treat analysis, the plaque-identifying toothpaste reduced mean plaque score by 49%, compared with a 24% reduction in placebo (P = .001). In a prespecified subgroup analysis of 38 subjects with baseline levels >0.5 mg/L, the plaque-identifying toothpaste reduced hs-CRP by 29%, compared with a 25% increase in placebo toothpaste (P = .041). This plaque-identifying toothpaste produced statistically significant reductions in dental plaque and hs-CRP. The observed reduction in dental plaque confirms and extends a previous observation. The observed reduction in inflammation supports the hypothesis of a reduction in risks of cardiovascular disease. The direct test of this hypothesis requires a large-scale randomized trial of sufficient size and duration designed a priori to do so. Such a finding would have major clinical and public health implications. Copyright © 2017 Elsevier Inc. All rights reserved.

Impact of Wall Shear Stress and Pressure Variation on the Stability of Atherosclerotic Plaque

NASA Astrophysics Data System (ADS)

Taviani, V.; Li, Z. Y.; Sutcliffe, M.; Gillard, J.

Rupture of vulnerable atheromatous plaque in the carotid and coronary arteries often leads to stroke and heart attack respectively. The mechanism of blood flow and plaque rupture in stenotic arteries is still not fully understood. A three dimensional rigid wall model was solved under steady and unsteady conditions assuming a time-varying inlet velocity profile to investigate the relative importance of axial forces and pressure drops in arteries with asymmetric stenosis. Flow-structure interactions were investigated for the same geometry and the results were compared with those retrieved with the corresponding one dimensional models. The Navier-Stokes equations were used as the governing equations for the fluid. The tube wall was assumed linearly elastic, homogeneous isotropic. The analysis showed that wall shear stress is small (less than 3.5%) with respect to pressure drop throughout the cycle even for severe stenosis. On the contrary, the three dimensional behavior of velocity, pressure and wall shear stress is in general very different from that predicted by one dimensional models. This suggests that the primary source of mistakes in one dimensional studies comes from neglecting the three dimensional geometry of the plaque. Neglecting axial forces only involves minor errors.

Role of infrasound pressure waves in atherosclerotic plaque rupture: a theoretical approach.

PubMed

Tsatsaris, Athanasios; Koukounaris, Efstathios; Motsakos, Theodoros; Perrea, Despina

2007-01-01

To investigate the role of infrasound aortic pressure waves (IPW) in atherosclerotic plaque rupture. Atherosclerotic plaques have been simulated partly, in two dimensions, as being short or long Conical Intersections (CIS), that is to say elliptic, parabolic or hyperbolic surfaces. Consequently, the course and reflection of the generated aortic pressure wave (infrasound domain-less than 20Hz) has been examined around the simulated plaques. The incidence of IPW on plaque surface results both in reflection and "refraction" of the wave. The IPW course within tissue, seems to be enhanced by high Cu-level presence at these areas according to recent evidence (US2003000388213). The "refracted", derived wave travels through plaque tissue and is eventually accumulated to the foci of the respective CIS-plaque geometry. The foci location within or underneath atheroma declares zones where infrasound energy is mostly absorbed. This process, among other mechanisms may contribute to plaque rupture through the development of local hemorrhage and inflammation in foci areas. In future, detection of foci areas and repair (i.e. via Laser Healing Microtechnique) may attenuate atherosclerotic plaque rupture behavior.

Vulnerable Atherosclerotic Plaque Elasticity Reconstruction Based on a Segmentation-Driven Optimization Procedure Using Strain Measurements: Theoretical Framework

PubMed Central

Le Floc’h, Simon; Tracqui, Philippe; Finet, Gérard; Gharib, Ahmed M.; Maurice, Roch L.; Cloutier, Guy; Pettigrew, Roderic I.

2016-01-01

It is now recognized that prediction of the vulnerable coronary plaque rupture requires not only an accurate quantification of fibrous cap thickness and necrotic core morphology but also a precise knowledge of the mechanical properties of plaque components. Indeed, such knowledge would allow a precise evaluation of the peak cap-stress amplitude, which is known to be a good biomechanical predictor of plaque rupture. Several studies have been performed to reconstruct a Young’s modulus map from strain elastograms. It seems that the main issue for improving such methods does not rely on the optimization algorithm itself, but rather on preconditioning requiring the best estimation of the plaque components’ contours. The present theoretical study was therefore designed to develop: 1) a preconditioning model to extract the plaque morphology in order to initiate the optimization process, and 2) an approach combining a dynamic segmentation method with an optimization procedure to highlight the modulogram of the atherosclerotic plaque. This methodology, based on the continuum mechanics theory prescribing the strain field, was successfully applied to seven intravascular ultrasound coronary lesion morphologies. The reconstructed cap thickness, necrotic core area, calcium area, and the Young’s moduli of the calcium, necrotic core, and fibrosis were obtained with mean relative errors of 12%, 4% and 1%, 43%, 32%, and 2%, respectively. PMID:19164080

Dickkopf1 destabilizes atherosclerotic plaques and promotes plaque formation by inducing apoptosis of endothelial cells through activation of ER stress

PubMed Central

Di, Mingxue; Wang, Lin; Li, Mengmeng; Zhang, Yu; Liu, Xinxin; Zeng, Renya; Wang, Han; Chen, Yifei; Chen, Weijia; Zhang, Yun; Zhang, Mei

2017-01-01

Several clinical studies reported that Dickkopf1 (DKK1) plasma levels are correlated with atherosclerosis. However, the impact of DKK1 on the formation and vulnerability of atherosclerotic plaques remains elusive. This study investigated DKK1’s effects on enlargement and destabilization of plaques by targeting endothelial cells and assessing the possible cellular mechanisms involved. The effects of DKK1 on atherogenesis and plaque stability were evaluated in ApoE−/− mice using lentivirus injections to knockdown and knock-in the DKK1 gene. The presence of DKK1 resulted in enlarged and destabilized atherosclerotic lesions and increased apoptosis, while silencing of DKK1 alleviated plaque formation and vulnerability in the whole progression of atherosclerosis. DKK1 expression was upregulated in response to ox-LDL treatment in a time- and concentration-dependent manner on human umbilical vein endothelial cell (HUVEC). The interference of DKK1 reversed ox-LDL-induced apoptosis in HUVECs. The mechanism underlying this effect was DKK1’s activation of the JNK signal transduction pathway and inhibition of canonical Wnt signaling, following by activation of the IRE1α and eif2α/CHOP pathways. In conclusion, DKK1 promotes plaque formation and vulnerability partly by inducing apoptosis in endothelial cells, which partly through inducing the JNK-endoplasmic reticulum stress pathway and inhibiting canonical Wnt signaling. PMID:28703797

Gap junctions contain different amounts of cholesterol which undergo unique sequestering processes during fiber cell differentiation in the embryonic chicken lens.

PubMed

Biswas, Sondip K; Lo, Woo-Kuen

2007-03-09

To determine the possible changes in the distribution of cholesterol in gap junction plaques during fiber cell differentiation and maturation in the embryonic chicken lens. The possible mechanism by which cholesterol is removed from gap junction plaques is also investigated. Filipin cytochemistry in conjunction with freeze-fracture TEM was used to visualize cholesterol, as represented by filipin-cholesterol complexes (FCCs) in gap junction plaques. Quantitative analysis on the heterogeneous distribution of cholesterol in gap junction plaques was conducted from outer and inner cortical regions. A novel technique combining filipin cytochemistry with freeze-fracture replica immunogold labeling (FRIL) was used to label Cx45.6 and Cx56 antibodies in cholesterol-containing gap junctions. Filipin cytochemistry and freeze-fracture TEM and thin-section TEM were used to examine the appearance and nature of the cholesterol-containing vesicular structures associated with gap junction plaques. Chicken lens fibers contain cholesterol-rich, cholesterol-intermediate and cholesterol-free gap junction populations in both outer and inner cortical regions. Filipin cytochemistry and FRIL studies confirmed that cholesterol-containing junctions were gap junctions. Quantitative analysis showed that approximately 86% of gap junctions in the outer cortical zone were cholesterol-rich gap junctions, whereas approximately 81% of gap junctions in the inner cortical zone were cholesterol-free gap junctions. A number of pleiomorphic cholesterol-rich vesicles of varying sizes were often observed in the gap junction plaques. They appear to be involved in the removal of cholesterol from gap junction plaques through endocytosis. Gap junctions in the young fibers are enriched with cholesterol because they are assembled in the unique cholesterol-rich cell membranes in the lens. A majority of cholesterol-rich gap junctions in the outer young fibers are transformed into cholesterol-free ones in the inner mature fibers during fiber cell maturation. A distinct endocytotic process appears to be involved in removing cholesterol from the cholesterol-containing gap junctions, and it may play a major role in the transformation of cholesterol-rich gap junctions into cholesterol-free ones during fiber cell maturation.

Plaque-left-behind after brushing: intra-oral reservoir for antibacterial toothpaste ingredients.

PubMed

Otten, Marieke P T; Busscher, Henk J; Abbas, Frank; van der Mei, Henny C; van Hoogmoed, Chris G

2012-10-01

Plaque is never fully removed by brushing and may act as a reservoir for antibacterial ingredients, contributing to their substantive action. This study investigates the contribution of plaque-left-behind and saliva towards substantivity of three antibacterial toothpastes versus a control paste without antibacterial claims. First, volunteers brushed 2 weeks with a control or antibacterial toothpaste. Next, plaque and saliva samples were collected 6 and 12 h after brushing and bacterial concentrations and viabilities were measured. The contributions of plaque and saliva towards substantivity were determined by combining control plaques with experimental plaque or saliva samples and subsequently assessing their viabilities. Bacterial compositions in the various plaque and saliva samples were compared using denaturing gradient gel electrophoresis. The viabilities of plaques after brushing with Colgate-Total® and Crest-Pro-Health® were smaller than of control plaques and up to 12 h after brushing with Crest-Pro-Health® plaques still contained effective, residual antibacterial activity against control plaques. No effective, residual antibacterial activity could be measured in saliva samples after brushing. There was no significant difference in bacterial composition of plaque or saliva after brushing with the different toothpastes. Plaque-left-behind after mechanical cleaning contributes to the substantive action of an antibacterial toothpaste containing stannous fluoride (Crest-Pro-Health®). The absorptive capacity of plaque-left-behind after brushing is of utmost clinical importance, since plaque is predominantly left behind in places where its removal and effective killing matter most. Therewith this study demonstrates a clear and new beneficial effect of the use of antibacterial toothpastes.

Microbial profiling of dental plaque from mechanically ventilated patients

PubMed Central

Twigg, Joshua A.; Lewis, Michael A. O.; Wise, Matt P.; Marchesi, Julian R.; Smith, Ann; Wilson, Melanie J.; Williams, David W.

2016-01-01

Micro-organisms isolated from the oral cavity may translocate to the lower airways during mechanical ventilation (MV) leading to ventilator-associated pneumonia (VAP). Changes within the dental plaque microbiome during MV have been documented previously, primarily using culture-based techniques. The aim of this study was to use community profiling by high throughput sequencing to comprehensively analyse suggested microbial changes within dental plaque during MV. Bacterial 16S rDNA gene sequences were obtained from 38 samples of dental plaque sampled from 13 mechanically ventilated patients and sequenced using the Illumina platform. Sequences were processed using Mothur, applying a 97 % gene similarity cut-off for bacterial species level identifications. A significant ‘microbial shift’ occurred in the microbial community of dental plaque during MV for nine out of 13 patients. Following extubation, or removal of the endotracheal tube that facilitates ventilation, sampling revealed a decrease in the relative abundance of potential respiratory pathogens and a compositional change towards a more predominantly (in terms of abundance) oral microbiota including Prevotella spp., and streptococci. The results highlight the need to better understand microbial shifts in the oral microbiome in the development of strategies to reduce VAP, and may have implications for the development of other forms of pneumonia such as community-acquired infection. PMID:26690690

Microbial profiling of dental plaque from mechanically ventilated patients.

PubMed

Sands, Kirsty M; Twigg, Joshua A; Lewis, Michael A O; Wise, Matt P; Marchesi, Julian R; Smith, Ann; Wilson, Melanie J; Williams, David W

2016-02-01

Micro-organisms isolated from the oral cavity may translocate to the lower airways during mechanical ventilation (MV) leading to ventilator-associated pneumonia (VAP). Changes within the dental plaque microbiome during MV have been documented previously, primarily using culture-based techniques. The aim of this study was to use community profiling by high throughput sequencing to comprehensively analyse suggested microbial changes within dental plaque during MV. Bacterial 16S rDNA gene sequences were obtained from 38 samples of dental plaque sampled from 13 mechanically ventilated patients and sequenced using the Illumina platform. Sequences were processed using Mothur, applying a 97% gene similarity cut-off for bacterial species level identifications. A significant 'microbial shift' occurred in the microbial community of dental plaque during MV for nine out of 13 patients. Following extubation, or removal of the endotracheal tube that facilitates ventilation, sampling revealed a decrease in the relative abundance of potential respiratory pathogens and a compositional change towards a more predominantly (in terms of abundance) oral microbiota including Prevotella spp., and streptococci. The results highlight the need to better understand microbial shifts in the oral microbiome in the development of strategies to reduce VAP, and may have implications for the development of other forms of pneumonia such as community-acquired infection.

Bacterial Diversity and Community Structure of Supragingival Plaques in Adults with Dental Health or Caries Revealed by 16S Pyrosequencing

PubMed Central

Xiao, Cuicui; Ran, Shujun; Huang, Zhengwei; Liang, Jingping

2016-01-01

Dental caries has a polymicrobial etiology within the complex oral microbial ecosystem. However, the overall diversity and structure of supragingival plaque microbiota in adult dental health and caries are not well understood. Here, 160 supragingival plaque samples from patients with dental health and different severities of dental caries were collected for bacterial genomic DNA extraction, pyrosequencing by amplification of the 16S rDNA V1–V3 hypervariable regions, and bioinformatic analysis. High-quality sequences (2,261,700) clustered into 10,365 operational taxonomic units (OTUs; 97% identity), representing 453 independent species belonging to 122 genera, 66 families, 34 orders, 21 classes, and 12 phyla. All groups shared 7522 OTUs, indicating the presence of a core plaque microbiome. α diversity analysis showed that the microbial diversity in healthy plaques exceeded that of dental caries, with the diversity decreasing gradually with the severity of caries. The dominant phyla of plaque microbiota included Bacteroidetes, Actinobacteria, Proteobacteria, Firmicutes, Fusobacteria, and TM7. The dominant genera included Capnocytophaga, Prevotella, Actinomyces, Corynebacterium, Neisseria, Streptococcus, Rothia, and Leptotrichia. β diversity analysis showed that the plaque microbial community structure was similar in all groups. Using LEfSe analysis, 25 differentially abundant taxa were identified as potential biomarkers. Key genera (27) that potentially contributed to the differential distributions of plaque microbiota between groups were identified by PLS-DA analysis. Finally, co-occurrence network analysis and function predictions were performed. Treatment strategies directed toward modulating microbial interactions and their functional output should be further developed. PMID:27499752

Asbestos-related diseases in automobile mechanics.

PubMed

Ameille, Jacques; Rosenberg, Nicole; Matrat, Mireille; Descatha, Alexis; Mompoint, Dominique; Hamzi, Lounis; Atassi, Catherine; Vasile, Manuela; Garnier, Robert; Pairon, Jean-Claude

2012-01-01

Automobile mechanics have been exposed to asbestos in the past, mainly due to the presence of chrysotile asbestos in brakes and clutches. Despite the large number of automobile mechanics, little is known about the non-malignant respiratory diseases observed in this population. The aim of this retrospective multicenter study was to analyse the frequency of pleural and parenchymal abnormalities on high-resolution computed tomography (HRCT) in a population of automobile mechanics. The study population consisted of 103 automobile mechanics with no other source of occupational exposure to asbestos, referred to three occupational health departments in the Paris area for systematic screening of asbestos-related diseases. All subjects were examined by HRCT and all images were reviewed separately by two independent readers; who in the case of disagreement discussed until they reached agreement. Multiple logistic regression models were constructed to investigate factors associated with pleural plaques. Pleural plaques were observed in five cases (4.9%) and interstitial abnormalities consistent with asbestosis were observed in one case. After adjustment for age, smoking status, and a history of non-asbestos-related respiratory diseases, multiple logistic regression models showed a significant association between the duration of exposure to asbestos and pleural plaques. The asbestos exposure experienced by automobile mechanics may lead to pleural plaques. The low prevalence of non-malignant asbestos-related diseases, using a very sensitive diagnostic tool, is in favor of a low cumulative exposure to asbestos in this population of workers.

Asbestos-related diseases in automobile mechanics

PubMed Central

Ameille, Jacques; Rosenberg, Nicole; Matrat, Mireille; Descatha, Alexis; Mompoint, Dominique; Hamzi, Lounis; Atassi, Catherine; Vasile, Manuela; Garnier, Robert; Pairon, Jean-Claude

2012-01-01

Purpose Automobile mechanics have been exposed to asbestos in the past, mainly due to the presence of chrysotile asbestos in brakes and clutches. Despite the large number of automobile mechanics, little is known about the non-malignant respiratory diseases observed in this population. The aim of this retrospective multicenter study was to analyze the frequency of pleural and parenchymal abnormalities on HRCT in a population of automobile mechanics. Methods The study population consisted of 103 automobile mechanics with no other source of occupational exposure to asbestos, referred to three occupational health departments in the Paris area for systematic screening of asbestos–related diseases. All subjects were examined by HRCT and all images were reviewed separately by two independent readers, with further consensus in the case of disagreement. Multiple logistic regression models were constructed to investigate factors associated with pleural plaques. Results Pleural plaques were observed in 5 cases (4.9%) and interstitial abnormalities consistent with asbestosis were observed in 1 case. After adjustment for age, smoking status, and a history of non-asbestos-related respiratory diseases, multiple logistic regression models showed a significant association between the duration of exposure to asbestos and pleural plaques. Conclusions The asbestos exposure experienced by automobile mechanics may lead to pleural plaques. The low prevalence of non-malignant asbestos-related diseases, using a very sensitive diagnostic tool, is in favor of a low cumulative exposure to asbestos in this population of workers. PMID:21965465

Graphical Modeling of Gene Expression in Monocytes Suggests Molecular Mechanisms Explaining Increased Atherosclerosis in Smokers

PubMed Central

Verdugo, Ricardo A.; Zeller, Tanja; Rotival, Maxime; Wild, Philipp S.; Münzel, Thomas; Lackner, Karl J.; Weidmann, Henri; Ninio, Ewa; Trégouët, David-Alexandre; Cambien, François; Blankenberg, Stefan; Tiret, Laurence

2013-01-01

Smoking is a risk factor for atherosclerosis with reported widespread effects on gene expression in circulating blood cells. We hypothesized that a molecular signature mediating the relation between smoking and atherosclerosis may be found in the transcriptome of circulating monocytes. Genome-wide expression profiles and counts of atherosclerotic plaques in carotid arteries were collected in 248 smokers and 688 non-smokers from the general population. Patterns of co-expressed genes were identified by Independent Component Analysis (ICA) and network structure of the pattern-specific gene modules was inferred by the PC-algorithm. A likelihood-based causality test was implemented to select patterns that fit models containing a path “smoking→gene expression→plaques”. Robustness of the causal inference was assessed by bootstrapping. At a FDR ≤0.10, 3,368 genes were associated to smoking or plaques, of which 93% were associated to smoking only. SASH1 showed the strongest association to smoking and PPARG the strongest association to plaques. Twenty-nine gene patterns were identified by ICA. Modules containing SASH1 and PPARG did not show evidence for the “smoking→gene expression→plaques” causality model. Conversely, three modules had good support for causal effects and exhibited a network topology consistent with gene expression mediating the relation between smoking and plaques. The network with the strongest support for causal effects was connected to plaques through SLC39A8, a gene with known association to HDL-cholesterol and cellular uptake of cadmium from tobacco, while smoking was directly connected to GAS6, a gene reported to have anti-inflammatory effects in atherosclerosis and to be up-regulated in the placenta of women smoking during pregnancy. Our analysis of the transcriptome of monocytes recovered genes relevant for association to smoking and atherosclerosis, and connected genes that before, were only studied in separate contexts. Inspection of correlation structure revealed candidates that would be missed by expression-phenotype association analysis alone. PMID:23372645

Short-term effects of povidone iodine and sodium fluoride therapy on plaque levels and microbiome diversity.

PubMed

Reilly, C; Goettl, M; Steinmetz, M; Nikrad, J; Jones, R S

2016-03-01

The objective of this study is to evaluate the effect of short-term changes in the oral microbial ecology of dental plaque and plaque levels after topical treatment of a combination of 10% povidone iodine (PI) and 5% sodium fluoride varnish (FV). A single group design intervention study on 12 pediatric patients, who underwent two baseline plaques samplings before the intervention, were enrolled in the study. A modified mixed dentition Silness-Löe plaque index score was used to assess plaque accumulation and microbial composition was assessed by amplicon sequencing analysis of the 16S rRNA V4 region. Dental plaque accumulation (P = 0.0424) was reduced after 1 week using PI/FV application. This reduction was not observed between the two double-baseline visits. 16S rRNA analysis showed that the single PI/FV therapy did not have dramatic shifts in the plaque microbiome community depicted by hierarchical cluster and principle component analysis. More subtle changes were found when analyzing the Shannon diversity index after the application of PI/FV vs two baselines prior to combination therapy. The bacteria within the dental biofilms showed resilience in maintaining the overall community diversity but reduced biofilm accumulation following PI/FV therapy. Repeated uses of PI/FV may augment plaque control during dental rehabilitation in children. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Directional spatial frequency analysis of lipid distribution in atherosclerotic plaque

NASA Astrophysics Data System (ADS)

Korn, Clyde; Reese, Eric; Shi, Lingyan; Alfano, Robert; Russell, Stewart

2016-04-01

Atherosclerosis is characterized by the growth of fibrous plaques due to the retention of cholesterol and lipids within the artery wall, which can lead to vessel occlusion and cardiac events. One way to evaluate arterial disease is to quantify the amount of lipid present in these plaques, since a higher disease burden is characterized by a higher concentration of lipid. Although therapeutic stimulation of reverse cholesterol transport to reduce cholesterol deposits in plaque has not produced significant results, this may be due to current image analysis methods which use averaging techniques to calculate the total amount of lipid in the plaque without regard to spatial distribution, thereby discarding information that may have significance in marking response to therapy. Here we use Directional Fourier Spatial Frequency (DFSF) analysis to generate a characteristic spatial frequency spectrum for atherosclerotic plaques from C57 Black 6 mice both treated and untreated with a cholesterol scavenging nanoparticle. We then use the Cauchy product of these spectra to classify the images with a support vector machine (SVM). Our results indicate that treated plaque can be distinguished from untreated plaque using this method, where no difference is seen using the spatial averaging method. This work has the potential to increase the effectiveness of current in-vivo methods of plaque detection that also use averaging methods, such as laser speckle imaging and Raman spectroscopy.

Influence of Adaptive Statistical Iterative Reconstruction on coronary plaque analysis in coronary computed tomography angiography.

PubMed

Precht, Helle; Kitslaar, Pieter H; Broersen, Alexander; Dijkstra, Jouke; Gerke, Oke; Thygesen, Jesper; Egstrup, Kenneth; Lambrechtsen, Jess

The purpose of this study was to study the effect of iterative reconstruction (IR) software on quantitative plaque measurements in coronary computed tomography angiography (CCTA). Thirty patients with a three clinical risk factors for coronary artery disease (CAD) had one CCTA performed. Images were reconstructed using FBP, 30% and 60% adaptive statistical IR (ASIR). Coronary plaque analysis was performed as per patient and per vessel (LM, LAD, CX and RCA) measurements. Lumen and vessel volumes and plaque burden measurements were based on automatic detected contours in each reconstruction. Lumen and plaque intensity measurements and HU based plaque characterization were based on corrected contours copied to each reconstruction. No significant changes between FBP and 30% ASIR were found except for lumen- (-2.53 HU) and plaque intensities (-1.28 HU). Between FBP and 60% ASIR the change in total volume showed an increase of 0.94%, 4.36% and 2.01% for lumen, plaque and vessel, respectively. The change in total plaque burden between FBP and 60% ASIR was 0.76%. Lumen and plaque intensities decreased between FBP and 60% ASIR with -9.90 HU and -1.97 HU, respectively. The total plaque component volume changes were all small with a maximum change of -1.13% of necrotic core between FBP and 60% ASIR. Quantitative plaque measurements only showed modest differences between FBP and the 60% ASIR level. Differences were increased lumen-, vessel- and plaque volumes, decreased lumen- and plaque intensities and a small percentage change in the individual plaque component volumes. Copyright © 2016 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

Modeling of Mechanical Stress Exerted by Cholesterol Crystallization on Atherosclerotic Plaques.

PubMed

Luo, Yuemei; Cui, Dongyao; Yu, Xiaojun; Chen, Si; Liu, Xinyu; Tang, Hongying; Wang, Xianghong; Liu, Linbo

2016-01-01

Plaque rupture is the critical cause of cardiovascular thrombosis, but the detailed mechanisms are not fully understood. Recent studies have found abundant cholesterol crystals in ruptured plaques, and it has been proposed that the rapid expansion of cholesterol crystals in a limited space during crystallization may contribute to plaque rupture. To evaluate the effect of cholesterol crystal growth on atherosclerotic plaques, we modeled the expansion of cholesterol crystals during the crystallization process in the necrotic core and estimated the stress on the thin cap with different arrangements of cholesterol crystals. We developed a two-dimensional finite element method model of atherosclerotic plaques containing expanding cholesterol crystals and investigated the effect of the magnitude and distribution of crystallization on the peak circumferential stress born by the cap. Using micro-optical coherence tomography (μOCT), we extracted the cross-sectional geometric information of cholesterol crystals in human atherosclerotic aorta tissue ex vivo and applied the information to the model. The results demonstrate that (1) the peak circumference stress is proportionally dependent on the cholesterol crystal growth; (2) cholesterol crystals at the cap shoulder impose the highest peak circumference stress; and (3) spatial distributions of cholesterol crystals have a significant impact on the peak circumference stress: evenly distributed cholesterol crystals exert less peak circumferential stress on the cap than concentrated crystals.

Relationship between thin cap fibroatheroma identified by virtual histology and angioscopic yellow plaque in quantitative analysis with colorimetry.

PubMed

Yamamoto, Masanori; Takano, Masamichi; Okamatsu, Kentaro; Murakami, Daisuke; Inami, Shigenobu; Xie, Yong; Seimiya, Koji; Ohba, Takayoshi; Seino, Yoshihiko; Mizuno, Kyoichi

2009-03-01

Thin cap fibroatheroma (TCFA) is considered to be a vulnerable plaque. Virtual Histology-intravascular ultrasound (VH-IVUS) can precisely identify TCFA in vivo. Intense yellow plaque on angioscopy determined by quantitative colorimetry with L a b color space corresponds with histological TCFA; in particular, a plaque of color b value >23 indicates an atheroma with a fibrous cap thickness <100 mum. In the present study, the relationship between VH-TCFA and angioscopic plaque color determined by colorimetry was investigated. Fifty-seven culprit plaques in 57 patients were evaluated by VH-IVUS and angioscopy. VH-TCFA was defined as a plaque with a necrotic core >10% of plaque area without overlying fibrous tissue, and angioscopic TCFA was a plaque with b value >23. The frequency of angioscopic TCFA was higher in the VH-TCFA group than in the VH-non-TCFA group (74% vs 23%, P=0.0002). Moreover, yellow color intensity (b value) significantly correlated with plaque classification on VH-IVUS. When TCFA detected with angioscopy was used as the gold standard, the sensitivity, specificity, and accuracy for TCFA with VH-IVUS was 68%, 81%, and 75%, respectively. VH-TCFA strongly correlated with angioscopic TCFA determined by a quantitative analysis with colorimetry.

Characterization of specimens obtained by different sampling methods for evaluation of periodontal bacteria.

PubMed

Okada, Ayako; Sogabe, Kaoru; Takeuchi, Hiroaki; Okamoto, Masaaki; Nomura, Yoshiaki; Hanada, Nobuhiro

2017-12-27

Quantitative analysis of periodontal bacteria is considered useful for clinical diagnosis, evaluation and assessment of the risk of periodontal disease. The purpose of this study was to compare the effectiveness of sampling of saliva, supragingival and subgingival plaque for evaluation of periodontal bacteria. From each of 12 subjects, i) subgingival plaque was collected from the deepest pocket using a sterile paper point, ii) stimulated whole saliva was collected after chewing gum, and iii) supragingival plaque was collected using a tooth brush. These samples were sent to the medical examination laboratory for quantitative analysis of the counts of three periodontal bacterial species: Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia. The proportions of these bacteria in subgingival plaque were higher than those in saliva or supragingival plaque, but lower in subgingival plaque than in saliva or supragingival plaque. In several cases, periodontal bacteria were below the levels of detection in subgingival plaque. We concluded that samples taken from subgingival plaque may be more useful for evaluating the proportion of periodontal bacteria in deep pockets than is the case for other samples. Therefore, for evaluation of periodontal bacteria, clinicians should consider the characteristics of the specimens obtained using different sampling methods.

Dental plaque biofilm in oral health and disease.

PubMed

Seneviratne, Chaminda Jayampath; Zhang, Cheng Fei; Samaranayake, Lakshman Perera

2011-01-01

Dental plaque is an archetypical biofilm composed of a complex microbial community. It is the aetiological agent for major dental diseases such as dental caries and periodontal disease. The clinical picture of these dental diseases is a net result of the cross-talk between the pathogenic dental plaque biofilm and the host tissue response. In the healthy state, both plaque biofilm and adjacent tissues maintain a delicate balance, establishing a harmonious relationship between the two. However, changes occur during the disease process that transform this 'healthy' dental plaque into a 'pathogenic' biofilm. Recent advances in molecular microbiology have improved the understanding of dental plaque biofilm and produced numerous clinical benefits. Therefore, it is imperative that clinicians keep abreast with these new developments in the field of dentistry. Better understanding of the molecular mechanisms behind dental diseases will facilitate the development of novel therapeutic strategies to establish a 'healthy dental plaque biofilm' by modulating both host and microbial factors. In this review, the present authors aim to summarise the current knowledge on dental plaque as a microbial biofilm and its properties in oral health and disease.

Computational Fluid Dynamics Simulations of Hemodynamics in Plaque Erosion

PubMed Central

Campbell, Ian C.; Timmins, Lucas H.; Giddens, Don P.; Virmani, Renu; Veneziani, Alessandro; Rab, S. Tanveer; Samady, Habib; McDaniel, Michael C.; Finn, Aloke V.; Taylor, W. Robert; Oshinski, John N.

2013-01-01

Purpose We investigated whether local hemodynamics were associated with sites of plaque erosion and hypothesized that patients with plaque erosion have locally elevated WSS magnitude in regions where erosion has occurred. Methods We generated 3D, patient-specific models of coronary arteries from biplane angiographic images in 3 human patients with plaque erosion diagnosed by optical coherence tomography (OCT). Using computational fluid dynamics, we simulated pulsatile blood flow and calculated both wall shear stress (WSS) and oscillatory shear index (OSI). We also investigated anatomic features of plaque erosion sites by examining branching and local curvature in x-ray angiograms of barium-perfused autopsy hearts. Results Neither high nor low magnitudes of mean WSS were associated with sites of plaque erosion. OSI and local curvature were also not associated with erosion. Anatomically, 8 of 13 hearts had a nearby bifurcation upstream of the site of plaque erosion. Conclusions This study provides preliminary evidence that neither hemodynamics nor anatomy are predictors of plaque erosion, based upon a very unique dataset. Our sample sizes are small, but this dataset suggests that high magnitudes of wall shear stress, one potential mechanism for inducing plaque erosion, are not necessary for erosion to occur. PMID:24223678

[Is regression of atherosclerotic plaque possible?

PubMed

Páramo, José A; Civeira, Fernando

As it is well-known, a thrombus evolving into a disrupted/eroded atherosclerotic plaque causes most acute coronary syndromes. Plaque stabilization via reduction of the lipid core and/or thickening of the fibrous cap is one of the possible mechanisms accounted for the clinical benefits displayed by different anti-atherosclerotic strategies. The concept of plaque stabilization was developed to explain how lipid-lowering agents could decrease adverse coronary events without substantial modifications of the atherosclerotic lesion ('angiographic paradox'). A number of imaging modalities (vascular ultrasound and virtual histology, MRI, optical coherence tomography, positron tomography, etc.) are used for non-invasive assessment of atherosclerosis; most of them can identify plaque volume and composition beyond lumen stenosis. An 'aggressive' lipid-lowering strategy is able to reduce the plaque burden and the incidence of cardiovascular events; this may be attributable, at least in part, to plaque-stabilizing effects. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

Effect of longitudinal anatomical mismatch of stenting on the mechanical environment in human carotid artery with atherosclerotic plaques.

PubMed

Fan, Zhenmin; Liu, Xiao; Sun, Anqiang; Zhang, Nan; Fan, Zhanming; Fan, Yubo; Deng, Xiaoyan

2017-10-01

Longitudinal anatomic mismatch (LAM) of stenting (i.e., a stenotic artery segment is not fully covered by a deployed stent) worsens the mechanical environment in the treated artery, which most likely is the cause for the associated high risks of restenosis, myocardial infarction and stent thrombosis. To probe the possibility, we constructed a patient-specific carotid model with two components of plaques (lipid and calcified plaque) based on MRI images; we numerically compared three different stenting scenarios in terms of von Mises stress (VMS) distribution in the treated arteries, namely, the short stenting (LAM), the medium stenting and the long stenting. The results showed that the short stenting led to more areas with abnormally high VMS along the inner surface of the treated artery with a much higher surface-averaged VMS at the distal end of the stent than both the medium and long stenting. While the VMS distribution in the calcified plaques was similar for the three stenting models, it was quite different in the lipid plaques among the three stenting models. The lipid plaque of the short-stent model showed more volume of the lipid plaque subjected to high VMS than those of the other two models. Based on the obtained results, we may infer that the short stenting (i.e., LAM) may aggravate vascular injury due to high VMS on the artery-stent interaction surface and within the lipid plaque. Therefore, to obtain a better outcome, a longer stent, rather than a short one, might be needed for arterial stenting. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.

Tanshinone II A stabilizes vulnerable plaques by suppressing RAGE signaling and NF-κB activation in apolipoprotein-E-deficient mice

PubMed Central

Zhao, Dong; Tong, Lufang; Zhang, Lixin; Li, Hong; Wan, Yingxin; Zhang, Tiezhong

2016-01-01

Tanshinone II A (TSIIA) is a diterpene quinone extracted from the roots of Salvia miltiorrhiza with anti-inflammatory and anti-oxidant properties that is used to treat atherosclerosis. In the current study, morphological analyses were conducted to evaluate the effects of TSIIA on atherosclerotic vulnerable plaque stability. Additionally, receptor of advanced glycation end products (RAGE), adhesion molecule, and matrix-metalloproteinases (MMPs) expression, and nuclear factor-κB (NF-κB) activation were examined in apolipoprotein E (apoE)-deficient mice treated with TSIIA. Eight-week-old apoE−/− mice were administered TSIIA and fed an atherogenic diet for 8 weeks. TSIIA exhibited no effects on plaque size. Analysis of the vulnerable plaque composition demonstrated decreased numbers of macrophages and smooth muscle cells, and increased collagen content in apoE-deficient mice treated with TSIIA compared with untreated mice. Western blotting revealed that TSIIA downregulated the expression levels of vascular cellular adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and MMP-2, −3, and −9, suppressed RAGE, and inhibited NF-κB, JNK and p38 activation. The present study demonstrated that the underlying mechanism of TSIIA stabilization of vulnerable plaques involves interfering with RAGE and NF-κB activation, and downregulation of downstream inflammatory factors, including ICAM-1, VCAM-1, and MMP-2, −3 and −9 in apoE−/− mice. PMID:27840935

Stress, social support, emotional regulation, and exacerbation of diffuse plaque psoriasis.

PubMed

Picardi, A; Mazzotti, E; Gaetano, P; Cattaruzza, M S; Baliva, G; Melchi, C F; Biondi, M; Pasquini, P

2005-01-01

The authors' aim was to investigate the role of stressful events, perceived social support, attachment security, and alexithymia in triggering exacerbations of diffuse plaque psoriasis. Inpatients experiencing a recent exacerbation of diffuse plaque psoriasis (N=33) were compared with inpatients with skin conditions believed to have a negligible psychosomatic component (N=73). Stressful events during the last year were assessed with Paykel's Interview for Recent Life Events. Attachment style, alexithymia, and perceived social support were assessed with the Experiences in Close Relationships questionnaire, the Toronto Alexithymia Scale, and the Multidimensional Scale of Perceived Social Support, respectively. Multiple logistic regression analysis was used to control for age, gender, education, marital status, and alcohol consumption. In relation to comparison subjects, the patients with psoriasis had lower perceived social support and higher attachment-related avoidance. Also, they were more likely to have high alexithymic characteristics. There were no differences between the patients with psoriasis and the comparison subjects in scores on the Experiences in Close Relationships anxiety scale, the total number of stressful events, and the number of undesirable, uncontrollable, or major events. Although caution should be applied in generalizing these findings to outpatients, this study suggests that alexithymia, attachment-related avoidance, and poor social support might increase susceptibility to exacerbations of diffuse plaque psoriasis, possibly through impaired emotional regulation. Several physiological mechanisms involving the neuroendocrine and the immune system might mediate the interplay between stress, personality, and diffuse plaque psoriasis.

Modeling plaque fissuring and dissection during balloon angioplasty intervention.

PubMed

Gasser, T Christian; Holzapfel, Gerhard A

2007-05-01

Balloon angioplasty intervention is traumatic to arterial tissue. Fracture mechanisms such as plaque fissuring and/or dissection occur and constitute major contributions to the lumen enlargement. However, these types of mechanically-based traumatization of arterial tissue are also contributing factors to both acute procedural complications and chronic restenosis of the treatment site. We propose physical and finite element models, which are generally useable to trace fissuring and/or dissection in atherosclerotic plaques during balloon angioplasty interventions. The arterial wall is described as an anisotropic, heterogeneous, highly deformable, nearly incompressible body, whereas tissue failure is captured by a strong discontinuity kinematics and a novel cohesive zone model. The numerical implementation is based on the partition of unity finite element method and the interface element method. The later is used to link together meshes of the different tissue components. The balloon angioplasty-based failure mechanisms are numerically studied in 3D by means of an atherosclerotic-prone human external iliac artery, with a type V lesion. Image-based 3D geometry is generated and tissue-specific material properties are considered. Numerical results show that in a primary phase the plaque fissures at both shoulders of the fibrous cap and stops at the lamina elastica interna. In a secondary phase, local dissections between the intima and the media develop at the fibrous cap location with the smallest thickness. The predicted results indicate that plaque fissuring and dissection cause localized mechanical trauma, but prevent the main portion of the stenosis from high stress, and hence from continuous tissue damage.

Aortic arch atherosclerosis in patients with severe aortic stenosis can be argued by greater day-by-day blood pressure variability.

PubMed

Iwata, Shinichi; Sugioka, Kenichi; Fujita, Suwako; Ito, Asahiro; Matsumura, Yoshiki; Hanatani, Akihisa; Takagi, Masahiko; Di Tullio, Marco R; Homma, Shunichi; Yoshiyama, Minoru

2015-07-01

Although it is well known that the prevalence of aortic arch plaques, one of the risk factors for ischemic stroke, is high in patients with severe aortic stenosis, the underlying mechanisms are not well understood. Increased day-by-day blood pressure (BP) variability is also known to be associated with stroke; however, little is known on the association between day-by-bay BP variability and aortic arch atherosclerosis in patients with aortic stenosis. Our objective was to clarify the association between day-by-day BP variables (average values and variability) and aortic arch atherosclerosis in patients with severe aortic stenosis. The study population consisted of 104 consecutive patients (mean age 75 ± 8 years) with severe aortic stenosis who were scheduled for aortic valve replacement. BP was measured in the morning in at least 4 consecutive days (mean 6.8 days) prior to the day of surgery. Large (≥4 mm), ulcerated, or mobile plaques were defined as complex plaques using transesophageal echocardiography. Cigarette smoking and all systolic BP variables were associated with the presence of complex plaques (p < 0.05), whereas diastolic BP variables were not. Multiple regression analysis indicated that day-by-day mean systolic BP and day-by-day systolic BP variability remained independently associated with the presence of complex plaques (p < 0.05) after adjustment for age, male sex, cigarette smoking, hypertension, hypercholesterolemia, and diabetes mellitus. These findings suggest that higher day-by-day mean systolic BP and day-by-day systolic BP variability are associated with complex plaques in the aortic arch and consequently stroke risk in patients with aortic stenosis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Analysis of the antibacterial activity and plaque control benefit of colgate total dentifrice via clinical evaluation and real-time polymerase chain reaction.

PubMed

Xu, Tao; Deshmukh, Meenal; Barnes, Virginia Monsul; Trivedi, Harsh M; Du-Thumm, Laurence; Richter, Rose; Cummins, Diane

2005-01-01

This study analyzed, from a combined clinical and molecular biologic perspective, the antibacterial and antiplaque efficacy of Colgate Total dentifrice (CTD). A single-blind crossover study design utilized 11 healthy human subjects. After a one-week washout period, subjects donated dental plaque, received a dental prophylaxis, and subsequently brushed with a test product. Twenty-four hours postbrushing, dental plaque was collected and a clinical plaque score determined. Dental plaque was submitted for Real-time Polymerase Chain Reaction (Real-time PCR) analysis. The same procedure was repeated in accordance with a crossover design for the use of the second test product. Following a one-week washout, a plaque donation, prophylaxis, and brushing with the test product ensued for each subject. Twenty-four hours post-brushing, the subjects returned for a plaque score and plaque donation. Twenty-four hours after brushing, dental plaque coverage increased 17.88% +/- 8.27% with CTD, compared to 30.42% +/- 9.97% with Colgate Cavity Protection (CCP; p = 0.005). Real-time PCR found plaque collected 24 hours after brushing with CTD exhibited, on average, fewer representative periodontal pathogens (Fusobacterium nucleatum, Actinobacillus actinomycetemcomitans, Tannerella forsythensis, and Porphyromonas gingivalis) and fewer early colonizers (Actinomyces naeslundii) than plaque collected before brushing, whereas CCP showed a moderate effect on oral bacteria. The study provides clinical and molecular biological evidence to substantiate the antibacterial and plaque control benefits of Colgate Total, and suggests the value of combining a molecular biological method with clinical research to corroborate clinical benefits.

Dental plaque development on a hydroxyapatite disk in young adults observed by using a barcoded pyrosequencing approach

PubMed Central

Takeshita, Toru; Yasui, Masaki; Shibata, Yukie; Furuta, Michiko; Saeki, Yoji; Eshima, Nobuoki; Yamashita, Yoshihisa

2015-01-01

Dental plaque is a dynamic microbial biofilm ecosystem that comprises hundreds of species including difficult-to-cultivate bacteria. We observed the assembly of a plaque bacterial community through 16S rRNA gene analysis. Plaque samples that accumulated on a hydroxyapatite disk for 1, 2, 3, 4, 5, and 7 days with saliva on day 0 were collected from 19 young adults using a removable resin splint. Quantitative PCR analysis showed that the total bacterial amount gradually increased and reached a plateau on day 4. Barcoded pyrosequencing analysis revealed that the microbial richness and diversity particularly increased between days 5 and 7. A principal coordinate analysis plot based on unweighted UniFrac showed the community assembly in a time-related manner, which became increasingly similar to the salivary microbiota. Facultative anaerobic bacteria such as Streptococcus, Neisseria, Abiotrophia, Gemella, and Rothia were predominant in the plaque bacterial community in the earlier days, whereas obligate anaerobes, such as Porphyromonas, Fusobacterium, Prevotella, and Capnocytophaga showed increased dominance on later days. UniFrac analysis also demonstrated that dental caries experience had a significant effect on the assembly process. Our results reveal the development pattern of the plaque bacterial community as well as the inter-individual differences associated with dental caries experience. PMID:25633431

Dental plaque development on a hydroxyapatite disk in young adults observed by using a barcoded pyrosequencing approach.

PubMed

Takeshita, Toru; Yasui, Masaki; Shibata, Yukie; Furuta, Michiko; Saeki, Yoji; Eshima, Nobuoki; Yamashita, Yoshihisa

2015-01-30

Dental plaque is a dynamic microbial biofilm ecosystem that comprises hundreds of species including difficult-to-cultivate bacteria. We observed the assembly of a plaque bacterial community through 16S rRNA gene analysis. Plaque samples that accumulated on a hydroxyapatite disk for 1, 2, 3, 4, 5, and 7 days with saliva on day 0 were collected from 19 young adults using a removable resin splint. Quantitative PCR analysis showed that the total bacterial amount gradually increased and reached a plateau on day 4. Barcoded pyrosequencing analysis revealed that the microbial richness and diversity particularly increased between days 5 and 7. A principal coordinate analysis plot based on unweighted UniFrac showed the community assembly in a time-related manner, which became increasingly similar to the salivary microbiota. Facultative anaerobic bacteria such as Streptococcus, Neisseria, Abiotrophia, Gemella, and Rothia were predominant in the plaque bacterial community in the earlier days, whereas obligate anaerobes, such as Porphyromonas, Fusobacterium, Prevotella, and Capnocytophaga showed increased dominance on later days. UniFrac analysis also demonstrated that dental caries experience had a significant effect on the assembly process. Our results reveal the development pattern of the plaque bacterial community as well as the inter-individual differences associated with dental caries experience.

A uni-extension study on the ultimate material strength and extreme extensibility of atherosclerotic tissue in human carotid plaques.

PubMed

Teng, Zhongzhao; Feng, Jiaxuan; Zhang, Yongxue; Sutcliffe, Michael P F; Huang, Yuan; Brown, Adam J; Jing, Zaiping; Lu, Qingsheng; Gillard, Jonathan H

2015-11-05

Atherosclerotic plaque rupture occurs when mechanical loading exceeds its material strength. Mechanical analysis has been shown to be complementary to the morphology and composition for assessing vulnerability. However, strength and stretch thresholds for mechanics-based assessment are currently lacking. This study aims to quantify the ultimate material strength and extreme extensibility of atherosclerotic components from human carotid plaques. Tissue strips of fibrous cap, media, lipid core and intraplaque hemorrhage/thrombus were obtained from 21 carotid endarterectomy samples of symptomatic patients. Uni-extension test with tissue strips was performed until they broke or slid. The Cauchy stress and stretch ratio at the peak loading of strips broken about 2mm away from the clamp were used to characterize their ultimate strength and extensibility. Results obtained indicated that ultimate strength of fibrous cap and media were 158.3 [72.1, 259.3] kPa (Median [Inter quartile range]) and 247.6 [169.0, 419.9] kPa, respectively; those of lipid and intraplaque hemorrhage/thrombus were 68.8 [48.5, 86.6] kPa and 83.0 [52.1, 124.9] kPa, respectively. The extensibility of each tissue type were: fibrous cap - 1.18 [1.10, 1.27]; media - 1.21 [1.17, 1.32]; lipid - 1.25 [1.11, 1.30] and intraplaque hemorrhage/thrombus - 1.20 [1.17, 1.44]. Overall, the strength of fibrous cap and media were comparable and so were lipid and intraplaque hemorrhage/thrombus. Both fibrous cap and media were significantly stronger than either lipid or intraplaque hemorrhage/thrombus. All atherosclerotic components had similar extensibility. Moreover, fibrous cap strength in the proximal region (closer to the heart) was lower than that of the distal. These results are helpful in understanding the material behavior of atherosclerotic plaques. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Contemporary perspective on plaque control.

PubMed

Marsh, P D

2012-06-22

The aim of this review article is to provide a scientific platform that will enable the dental team to develop a rational approach to plaque control based on the latest knowledge of the role of the oral microflora in health and disease. The resident oral microflora is natural and forms spatially-organised, interactive, multi-species biofilms on mucosal and dental surfaces in the mouth. These resident oral microbial communities play a key function in the normal development of the physiology of the host and are important in preventing colonisation by exogenous and often undesirable microbes. A dynamic balance exists between the resident microflora and the host in health, and disease results from a breakdown of this delicate relationship. Patients should be taught effective plaque control techniques that maintain dental biofilms at levels compatible with oral health so as to retain the beneficial properties of the resident microflora while reducing the risk of dental disease from excessive plaque accumulation. Antimicrobial and antiplaque agents in oral care products can augment mechanical plaque control by several direct and indirect mechanisms that not only involve reducing or removing dental biofilms but also include inhibiting bacterial metabolism when the agents are still present at sub-lethal concentrations.

Adherence to a Mediterranean diet is associated with the presence and extension of atherosclerotic plaques in middle-aged asymptomatic adults: The Aragon Workers' Health Study.

PubMed

Mateo-Gallego, Rocío; Uzhova, Irina; Moreno-Franco, Belén; León-Latre, Montserrat; Casasnovas, José A; Laclaustra, Martín; Peñalvo, José L; Civeira, Fernando

The Mediterranean diet (MeDi) is known to prevent cardiovascular events but the mechanisms mediating this association are not fully understood. The objective of the study was to examine the association between MeDi adherence and the presence and extent of atherosclerotic plaques in carotid, femoral, and aorta territories and its relationship with risk factors in asymptomatic middle-aged adults. Cross-sectional analysis of the Aragon Workers' Health Study, a cohort of 2588 subjects (94.9% men aged 51.3 ± 3.89 years) without previous cardiovascular history. Participants underwent carotid, femoral, and aorta ultrasound for the quantification of number and thickness of plaques and intima-media thickness. To estimate the participant's adherence to MeDi, we computed the Alternative MEDiterranean index (aMED). The overall aMED score was 4.19 ± 1.70, representing a moderate adherence to MeDi. aMED score was associated with the presence of plaque in femoral arteries (odds ratio highest vs lowest aMED score quartile: 0.63; 95% confidence interval: 0.48-0.83; P trend = .045) independently of risk factors and mediators. The strongest association between aMED quartiles and presence of plaque was found among smokers, both in femoral (0.39 [0.22-0.69]; P trend = .001) and in any territory (0.33 [0.14-0.79], P trend = .008). aMED was inversely associated with the number of plaques in all territories except for carotids. MeDi adherence showed a dose-dependent protective association with the presence, number, and thickness of plaques independent of other risk factors. The association was strongest for femoral arteries and among smokers. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Morphological differences in coronary arteries following rotational atherectomy versus balloon angioplasty: ultrasound and angioscopic observations

NASA Astrophysics Data System (ADS)

Bass, Theodore A.; Gilmore, Paul S.; White, Christopher J.; Chami, Youssef G.; Kircher, Barbara J.; Conetta, Donald A.

1993-09-01

Percutaneous transluminal coronary rotational atherectomy (PTCRA) is an exciting new device to recannulate obstructed coronary arteries. This device works as a high speed `drill,' selectively cutting hard atherosclerotic plaque while preferentially sparing the softer, less diseased vascular luminal surface. At speeds as high as 200,000 rpm the plaque is pulverized into small particles easily handled by the circulatory system with no untoward clinical sequela. Balloon angioplasty does not remove atherosclerotic plaque. It dilates the vessel by mechanically stretching, compressing and splitting the plaque and vessel lining. We compare morphological and surface luminal characteristics of vessels post PTCRA to vessels post PTCA.

In-depth proteomic analysis of the byssus from marine mussel Mytilus coruscus.

PubMed

Qin, Chuan-Li; Pan, Qi-Dong; Qi, Qi; Fan, Mei-Hua; Sun, Jing-Jing; Li, Nan-Nan; Liao, Zhi

2016-07-20

Mussels attach to various submerged surfaces by using the byssus, which contains different proteins and is a promising source of water-resistant bio-adhesives for potential use in biotechnological and medical applications. The protein composition of the byssus has not yet been fully understood although at least eleven byssal proteins were characterized previously. In order to increase genomic resources and identify new byssal proteins from mussel Mytilus coruscus, high-throughput Illumina sequencing was undertaken on the foot, and 79,997,776 paired-ends reads were generated, yielding a library containing 88,825ft unigenes. The M. coruscus byssus was divided into three parts, the proximal thread, the distal thread, and the plaque. Byssal proteins from each part of the byssus were analyzed by shotgun-LTQ analysis. The MS/MS spectra were searched against the foot unigenes dataset and 48 byssal proteins were identified from the M. coruscus byssus. From the whole set, 17, 5, and 11 proteins were exclusive to the proximal thread, the distal thread, and the plaque, respectively. These data can be used as a resource for further studies on the roles of byssal proteins in the deposition of different byssus parts (thread vs. plaque) or in the different mechanical properties (tenacity vs. adhesion). Byssal proteins are the major component that controls different aspects of the byssal formation process and thus a source of bioactive molecules that would offer interesting perspectives in biomaterials and bio-adhesive fields. In this paper, we characterized the protein set from different partsof Mytilus coruscus byssus by a combination of transcriptome/proteome technical. A whole set of 48 byssal proteins were described here, including proteins of collagen-like, C1q domain-containing, protease inhibitor-like, tyrosinase-like, SOD, and others. Thread (the distal portion and the proximal portion) and plaque showed distinct protein composition. Of the whole byssal protein set, 11 are exclusive to the plaque, 17 are exclusive to the proximal thread, and 5 are exclusive to the distal thread. Only four proteins are shared by all the three parts of the byssus. The new byssal proteins reported here represent a significant expansion of the knowledge base of Mytilus byssal proteins, and are important for further exploring the mechanism of adhesion in mussel. Copyright © 2016 Elsevier B.V. All rights reserved.

Aortic atherosclerotic plaque detection using a multiwavelength handheld photoacoustic imaging system

NASA Astrophysics Data System (ADS)

Hirano, Susumu; Namita, Takeshi; Kondo, Kengo; Yamakawa, Makoto; Shiina, Tsuyoshi

2016-03-01

Patients affected by diseases caused by arteriosclerosis are increasing. Atherosclerosis, which is becoming an especially difficult health problem, forms plaques from lipids such as cholesterol located in walls of the aorta, cerebral artery, and coronary artery. Because lipid-rich plaques are vulnerable and because arterial rupture causes acute vascular occlusion, early detection is crucially important to prevent plaque growth and rupture. Ultrasound systems can detect plaques but cannot discriminate between vulnerable and equable plaques. To evaluate plaques non-invasively and easily, we developed a handheld photoacoustic imaging device. Its usefulness was verified in phantom experiments with a bovine aorta in which mimic plaque had been embedded. Photoacoustic images taken at wavelengths that produce high light absorbance by lipids show strong photoacoustic signals from the boundary of the mimic plaque. Results confirmed that our system can evaluate plaque properties by analysis with the photoacoustic spectrum. The effects of surrounding tissues and tissue components on plaque evaluation were investigated using a layered phantom. The mimic plaque located under a 6 mm blood layer was also evaluated. Results of these analyses demonstrate the system's usefulness.

Calcium glycerophosphate and caries: a review of the literature.

PubMed

Lynch, R J M

2004-01-01

To review studies in the dental literature regarding the anti-caries mode of action of glycerophosphate with special reference to calcium glycerophosphate. The cariostatic properties of calcium glycerophosphate have been demonstrated during numerous in vivo and in vitro studies. Several mechanisms have been suggested and these include plaque-pH buffering, elevation of plaque calcium and phosphate levels and direct interaction with dental mineral. There is credible evidence that calcium glycerophosphate has the potential to reduce the progression of caries via all of these mechanisms if it is applied frequently and at a sufficiently high concentration. Reduction of plaque mass has also been proposed as a cariostatic mechanism but this seems less likely. Animal studies have shown that the calcium glycerophosphate/sodium monofluorophosphate system can have a greater anti-caries effect than sodium monofluorophosphate alone and this was subsequently confirmed in a caries clinical trial. We conclude that elevation of calcium levels in plaque is the most likely explanation and that any means of enhancing this effect has significant promise as a means to further increase in anti-caries potential of the calcium glycerophosphate/sodium monofluorophosphate system compared to sodium monofluorophosphate alone.

Ultrasound Assessment of Carotid Plaque Echogenicity Response to Statin Therapy: A Systematic Review and Meta-Analysis

PubMed Central

Ibrahimi, Pranvera; Jashari, Fisnik; Bajraktari, Gani; Wester, Per; Henein, Michael Y.

2015-01-01

Objective: To evaluate in a systematic review and meta-analysis model the effect of statin therapy on carotid plaque echogenicity assessed by ultrasound. Methods: We have systematically searched electronic databases (PubMed, MEDLINE, EMBASE and Cochrane Center Register) up to April, 2015, for studies evaluating the effect of statins on plaque echogenicity. Two researchers independently determined the eligibility of studies evaluating the effect of statin therapy on carotid plaque echogenicity that used ultrasound and grey scale median (GSM) or integrated back scatter (IBS). Results: Nine out of 580 identified studies including 566 patients’ carotid artery data were meta-analyzed for a mean follow up of 7.2 months. A consistent increase in the echogenicity of carotid artery plaques, after statin therapy, was reported. Pooled weighted mean difference % (WMD) on plaque echogenicity after statin therapy was 29% (95% CI 22%–36%), p < 0.001, I2 = 92.1%. In a meta-regression analysis using % mean changes of LDL, HDL and hsCRP as moderators, it was shown that the effects of statins on plaque echogenicity were related to changes in hsCRP, but not to LDL and HDL changes from the baseline. The effect of statins on the plaque was progressive; it showed significance after the first month of treatment, and the echogenicity continued to increase in the following six and 12 months. Conclusions: Statin therapy is associated with a favorable increase of carotid plaque echogenicity. This effect seems to be dependent on the period of treatment and hsCRP change from the baseline, independent of changes in LDL and HDL. PMID:25984600

Morphological Characterization of Thioflavin-S-Positive Amyloid Plaques in Transgenic Alzheimer Mice and Effect of Passive Aβ Immunotherapy on Their Clearance

PubMed Central

Bussière, Thierry; Bard, Frédérique; Barbour, Robin; Grajeda, Henry; Guido, Terry; Khan, Karen; Schenk, Dale; Games, Dora; Seubert, Peter; Buttini, Manuel

2004-01-01

Transgenic mice mimicking certain features of Alzheimer’s disease (AD)-pathology, namely amyloid plaques and neurofibrillary tangles, have been developed in an effort to better understand the mechanism leading to the formation of these characteristic cerebral lesions. More recently, these animal models have been widely used to investigate emergent therapies aimed at the reduction of the cerebral amyloid load. Several studies have shown that immunotherapy targeting the amyloid peptide (Aβ) is efficacious at clearing the amyloid plaques or preventing their formation, and at reducing the memory/behavior impairment observed in these animals. In AD, different types of plaques likely have different pathogenic significance, and further characterization of plaque pathology in the PDAPP transgenic mice would enhance the evaluation of potential therapeutics. In the present study, a morphological classification of amyloid plaques present in the brains of PDAPP mice was established by using Thioflavin-S staining. Neuritic dystrophy associated with amyloid plaques was also investigated. Finally, the efficacy of passive immunization with anti-Aβ antibodies on the clearance of Thio-S positive amyloid plaques was studied. Our results show that distinct morphological types of plaques are differentially cleared depending upon the isotype of the antibody. PMID:15331422

The occult aftermath of boxing.

PubMed Central

Roberts, G W; Allsop, D; Bruton, C

1990-01-01

The repeated head trauma experienced by boxers can lead to the development of dementia pugilistica (DP)--punch drunk syndrome. The neuropathology of DP in a classic report by Corsellis et al describes the presence of numerous neurofibrillary tangles in the absence of plaques, in contrast to the profusion of tangles and plaques seen in Alzheimer's disease (AD). The DP cases used in that report were re-investigated with immunocytochemical methods and an antibody raised to the beta-protein present in AD plaques. We found that all DP cases with substantial tangle formation showed evidence of extensive beta-protein immunoreactive deposits (plaques). These diffuse "plaques" were not visible with Congo-red or standard silver stains. The degree of beta-protein deposition was comparable to that seen in AD. Our data indicate that the present neuropathological description of DP (tangles but no plaques) should be altered to acknowledge the presence of substantial beta-protein deposition (plaques). The molecular markers present in the plaques and tangles of DP are the same as those in AD. Similarities in clinical symptoms, distribution of pathology and neurochemical deficits also exist. Epidemiological studies have shown that head injury is a risk factor in AD. It is probable that DP and AD share common pathogenic mechanisms leading to tangle and plaque formation. Images PMID:2191084

Involvement of histone methylation in macrophage apoptosis and unstable plaque formation in methionine-induced hyperhomocysteinemic ApoE-/- mice.

PubMed

Cong, Guangzhi; Yan, Ru; Huang, Hui; Wang, Kai; Yan, Ning; Jin, Ping; Zhang, Na; Hou, Jianjun; Chen, Dapeng; Jia, Shaobin

2017-03-15

Hyperhomocysteinemia (Hhcy) is an independent risk factor of atherosclerosis and promotes unstable plaque formation. Epigenetic mechanisms play an important role in the pathogenesis of atherosclerosis induced by Hhcy. However, the exact mechanism is still undefined. Lesional apoptotic cells and necrotic core formation contribute greatly to the progression of plaque. The present study sought to determine whether modification of histone methylation is involved in macrophage apoptosis and unstable plaque formation in the condition of Hhcy. The unstable plaque formation, lesional apoptotic cells and status of histone methylation were monitored in the aortas of Hhcy ApoE -/- mice induced by a high-methionine (HM) diet for 20weeks. Involvement of histone methylation in macrophage apoptosis and foam cell formation were assessed in macrophage Raw 264.7 cells after being challenged with homocysteine alone or in combination with the histone methylation inhibitor BIX 01294. The unstable plaque formation and lesion apoptotic cells are increased in ApoE -/ - mice supplemented with high-methionine (HM), accompanied with a decreased expression of histone H3 lysine 9 dimethylation. Hhcy increases the apoptosis of macrophages and inhibits the histone H3 lysine 9 dimethylation, as well as the expression of histone methyltransferase G9a in vitro. Inhibition of histone methylation by BIX01294 enhances macrophage apoptosis and foam cell formation in vitro. Our data suggest that Hhcy promotes the progression of atherosclerosis via macrophage apoptosis. Histone methylation might be involved in macrophage apoptosis and unstable plaque formation in methionine induced hyperhomocysteinemic ApoE -/- mice. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of Eicosapentaenoic and Docosahexaenoic Acids Added to Statin Therapy on Coronary Artery Plaque in Patients With Coronary Artery Disease: A Randomized Clinical Trial.

PubMed

Alfaddagh, Abdulhamied; Elajami, Tarec K; Ashfaque, Hasan; Saleh, Mohamad; Bistrian, Bruce R; Welty, Francine K

2017-12-15

Although statins reduce cardiovascular events, residual risk remains. Therefore, additional modalities are needed to reduce risk. We evaluated the effect of eicosapentaenoic acid and docosahexaenoic acid in pharmacologic doses added to statin treatment on coronary artery plaque volume. A total of 285 subjects with stable coronary artery disease on statins were randomized to omega-3 ethyl-ester (1.86 g of eicosapentaenoic acid and 1.5 g of docosahexaenoic acid daily) or no omega-3 (control) for 30 months. Coronary plaque volume was assessed by coronary computed tomographic angiography. Mean (SD) age was 63.0 (7.7) years; mean low-density lipoprotein cholesterol ≤80 mg/dL. In the intention-to-treat analysis, our primary endpoint, noncalcified plaque volume, was not different between groups ( P =0.14) but approached significance in the per protocol analysis ( P =0.07). When stratified by age in the intention-to-treat analysis, younger omega-3 subjects had significantly less progression of the primary endpoint, noncalcified plaque ( P =0.013), and fibrous, calcified and total plaque. In plaque subtype analysis, controls had significant progression of fibrous plaque compared to no change in the omega-3 ethyl-ester group (median % change [interquartile range], 5.0% [-5.7, 20.0] versus -0.1% [-12.3, 14.5], respectively; P =0.018). Among those on low-intensity statins, omega-3 ethyl-ester subjects had attenuation of fibrous plaque progression compared to controls (median % change [interquartile range], 0.3% [-12.8, 9.0] versus 4.8% [-5.1, 19.0], respectively; P =0.032). In contrast, those on high-intensity statins had no difference in plaque change in either treatment arm. High-dose eicosapentaenoic acid and docosahexaenoic acid provided additional benefit to statins in preventing progression of fibrous coronary plaque in subjects adherent to therapy with well-controlled low-density lipoprotein cholesterol levels. The benefit on low-intensity statin, but not high-intensity statin, suggests that statin intensity affects plaque volume. URL: http://www.ClinicalTrials.gov. Unique identifier: NCT01624727. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Advances in helical stent design and fabrication thermal treatment and structural interaction studies of the simulated plaque-laden artery

NASA Astrophysics Data System (ADS)

Welch, Tre Raymond

Advancements in processing biomaterials have lead to the development of bioresorbable PLLA drug-loaded stents with different geometric configurations. To further advance the technology, systematic studies have been carried out. This dissertation consists of five specific aims: (1) To characterize the effects of thermal annealing on the mechanical characteristics of PLLA helical stent, (2) To characterize the mechanical characteristics of a PLLA double helix stent, (3) To characterize the physical and chemical properties of PLLA films impregnated with niacin and curcumin, (4) To characterize the mechanical interaction of expanded stent and vascular wall with both model simulation and experimental studies using PDMS phantom arteries, (5) To simulate the stent-plaque-artery interactions using computer models. Results and their significances in bioresorbable PLLA drug-loaded stents technology as well as clinical prospects will be presented. For Aim1, thermal annealing is shown to improve mechanical characteristics of the helical stent, including pressure-diameter response curves, incremental stiffness, and collapse pressure. Differential scanning calorimetric analysis of stent fiber reveals that thermal annealing contribute to increased percent crystallinity, thus enhanced mechanical characteristics of the stent. For Aim 2, the new double helix design was shown to leads to improved mechanical characteristics of stent, including pressure-diameter response curves, incremental stiffness, and collapse pressure. Further, it was found to lead to an increased percent crystallinity and reduced degradation rate. For Aim 3, the changes in mechanical properties, crystallinity in PLLA polymer loaded with curcumin, or niacin, or both from that of control are clearly delineated. Results from Aim 4 shed lights on the mechanical disturbance in the vicinity of deployed stent and vascular wall as well as the abnormal shear stresses on the vascular endothelium. Their implications in triggering thrombi formation are discussed. Results from Aim 5 provided insights on the stent-plaque-artery mechanical interaction and how the altered mechanical environment after stent deployment could affect vascular remodeling and factors lead to re-stenosis. The significances of this work in advancing the bioresorbable PLLA drug-loaded stents technology as well as its clinical prospects are presented.

Effect of rosuvastatin on atherosclerotic plaque stability: An intravascular ultrasound elastography study.

PubMed

Li, Zhaohuan; Wang, Lin; Hu, Xiaobo; Zhang, Pengfei; Chen, Yifei; Liu, Xinxin; Xu, Mingjun; Zhang, Yun; Zhang, Mei

2016-05-01

The present study aimed to investigate the effect of potent rosuvastatin therapy on plaque mechanical stabilization as seen on IVUSE. 14 purebred New Zealand rabbits were fed a high-cholesterol diet; the abdominal aorta endothelium was balloon-injured after 2 weeks; at week 13, 7 rabbits received rosuvastatin (1.5 mg/kg/day), and the other 7 received an equal volume of saline. IVUS images of abdominal aortas were acquired, and 2 consecutive frames near the end-diastole images in situ were used to construct an IVUS elastogram. Control rabbits showed a significant increase in shear strain (SS) and area strain (AS) in total plaques. The rosuvastatin group showed no change in SS and AS, but serum TG and LDL-C levels were reduced, with less lipid deposition, macrophage infiltration, production of proinflammatory cytokines and apoptosis in plaques. The changes in SS and AS from baseline between groups significantly differed (SS: 1.15 (1.96) % vs. -0.99 ± 2.83%, p = 0.013; AS: 1.25 (2.29) % vs. -1.67 ± 5.05%, p = 0.022). At follow-up, for controls, strain values were increased in the shoulder of eccentric plaques (SS: 2.66 ± 1.31% vs. 4.86 ± 1.93%, p = 0.016; AS: 4.45 ± 2.33% vs. 7.91 ± 2.74%, p = 0.009) but not the plaque body. Changes in SS and AS in the plaque shoulder differed between the control and rosuvastatin groups (SS: 2.20 ± 2.17% vs. -0.87 ± 3.31%, p = 0.028; AS: 2.10 (4.61) % vs. -2.75 ± 5.97%, p = 0.009). Rosuvastatin therapy in rabbits with atherosclerotic plaques led to less vulnerable plaque features. IVUSE is a very sensitive technique for detecting pharmacologically-induced mechanical changes in rabbit atherosclerotic plaques. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Evaluation of carotid plaque vulnerability in vivo: Correlation between dynamic contrast-enhanced MRI and MRI-modified AHA classification.

PubMed

Ge, Xiaoqian; Zhou, Zien; Zhao, Huilin; Li, Xiao; Sun, Beibei; Suo, Shiteng; Hackett, Maree L; Wan, Jieqing; Xu, Jianrong; Liu, Xiaosheng

2017-09-01

To noninvasively monitor carotid plaque vulnerability by exploring the relationship between pharmacokinetic parameters (PPs) of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and plaque types based on MRI-modified American Heart Association (AHA) classification, as well as to assess the ability of PPs in discrimination between stable and vulnerable plaques suspected on MRI. Of 70 consecutive patients with carotid plaques who volunteered for 3.0T MRI (3D time-of-flight [TOF], T 1 -weighted, T 2 -weighted, 3D magnetization-prepared rapid acquisition gradient-echo [MP-RAGE] and DCE-MRI), 66 participants were available for analysis. After plaque classification according to MRI-modified AHA Lesion-Type (LT), PPs (K trans , k ep , v e , and v p ) of DCE-MRI were measured. The Extended Tofts model was used for calculation of PPs. For participants with multiple carotid plaques, the plaque with the worst MRI-modified AHA LT was chosen for analysis. Correlations between PPs and plaque types and the ability of these parameters to distinguish stable and vulnerable plaques suspected on MRI were assessed. Significant positive correlation between K trans and LT III to VI was found (ρ = 0.532, P < 0.001), as was the correlation between k ep and LT III to VI (ρ = 0.409, P < 0.001). Stable and vulnerable plaques suspected on MRI could potentially be distinguished by K trans (sensitivity 83%, specificity 100%) and k ep (sensitivity 77%, specificity 91%). K trans and k ep from DCE-MRI can provide quantitative information to monitor plaque vulnerability in vivo and differentiate vulnerable plaques suspected on MRI from stable ones. These two parameters could be adopted as imaging biomarkers for plaque characterization and risk stratification. 1 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:870-876. © 2017 International Society for Magnetic Resonance in Medicine.

A Novel Approach to the Elucidation of the Mechanism of Development of Androgen-Independent Growth of Prostate Cancer

DTIC Science & Technology

2001-01-01

with 1.0 with differential hybridization to the two probes. Phage plaques corresponding ml of RIPA buffer with protease inhibitors (PBS, 1% NP40, 0.5...hybridized to radiolabeled probe prepared from plaque-purified phage . at 10,000 X g for 20 min; supernatants were collected and centrifuged again to...Screening. Lambda phage plaques from the primary unamplified Differential expression screening of cDNA libraries constructed CWR22 library were plated

Mechanism of Polykaryocytosis Associated with Noncytopathic Infection by Measles Virus

PubMed Central

Atherton, John G.; Chaparas, Sotiros D.; Cremer, Martha; Gordon, Irving

1965-01-01

Atherton, John G. (University of Southern California, Los Angeles), Sotiros G. Chaparas, Martha Cremer, and Irving Gordon. Mechanism of polykaryocytosis associated with noncytopathic infection by measles virus. J. Bacteriol. 90:213–219. 1965.—Infection with a measles virus variant resulted not only in formation of polykaryocytes (PK) but also in formation of multicellular immunofluorescent foci (IFF) in which no cytopathic effect could be detected. The ratio of IFF to PK changed from 27 to 4 during the first passage and remained 4 after a second passage. PK were plaques. Plaque assay was linear in the presence of IFF. To investigate the mechanism of PK formation, radioautography was done on cells pulse-labeled with tritiated thymidine before virus multiplication began. The results showed that PK were formed by fusion; there were no PK whose nuclei contained no label, and the proportion of labeled nuclei (32%) and distribution of grain counts was the same in PK as in uninvolved cells, ruling out nuclear replication without concomitant cytoplasmic membrane formation as the mechanism of formation of these PK. Early in PK development, neutral red uptake was markedly increased (“red” plaques). As PK matured, hyperchromicity disappeared (“white” plaques). This sequence provided an index of rate of evolution of PK. Rate of PK maturation was more rapid at 37 than at 32 C. Images PMID:16562019

Evaluation of the biomechanics of atherosclerosis by acoustic microscopy

NASA Astrophysics Data System (ADS)

Saijo, Yoshifumi; Nitta, Shin-ichi; Schiott Jorgensen, Claus; Falk, Erling

2001-07-01

Acoustic microscopy provides not only the morphology, but also the biomechanical properties of the biological soft tissues. The biomechanics of atherosclerosis is important because the pathophysiology of atherosclerosis is closely related with mechanical properties and mechanical stress. Rupture of the fibrous cap of atheromatous plaque is the initial event in acute coronary syndrome such as acute myocardial infarction or unstable angina. In addition to extrinsic physical stresses to the plaque, the intrinsic biomechanical property of the plaque is important for assessing the mechanism of the rupture. Two sets of SAMs operating in 100 to 200 MHz and in 800 MHz to 1.3 GHz were equipped to measure the acoustic properties of atherosclerosis of human or mouse arteries. The values of attenuation and sound speed in the tissue components of atherosclerosis were measured by analyzing the frequency dependent characteristics of the amplitude and phase signals. Both values were highest in calcification and lowest in lipid pool. Although attenuation and sound speed were relatively high in intimal fibrosis, the inhomogeneity of acoustic parameters was found within the fibrous cap. Polarized microscopy for the collagen stained with Picrosirius red showed that the attenuation of ultrasound was significantly higher in type I collagen with orange polarized color compared to type III collagen with green color. SAM has shown the possibility to detect the plaque vulnerability and it might improve our understanding of the sudden rupture from micro-mechanical point of view.

Intraplaque stretch in carotid atherosclerotic plaque--an effective biomechanical predictor for subsequent cerebrovascular ischemic events.

PubMed

Teng, Zhongzhao; Sadat, Umar; Wang, Wenkai; Bahaei, Nasim S; Chen, Shengyong; Young, Victoria E; Graves, Martin J; Gillard, Jonathan H

2013-01-01

Stretch is a mechanical parameter, which has been proposed previously to affect the biological activities in different tissues. This study explored its utility in determining plaque vulnerability. One hundred and six patients with mild to moderate carotid stenosis were recruited in this study (53 symptomatic and 53 asymptomatic). High resolution, multi-sequence magnetic resonance (MR) imaging was performed to delineate various plaque components. Finite element method was used to predict high stretch concentration within the plaque. During a two-year follow-up, 11 patients in symptomatic group and 3 in asymptomatic group experienced recurrent cerebrovascular events. Plaque stretch at systole and stretch variation during one cardiac cycle was greater in symptomatic group than those in the asymptomatic. Within the symptomatic group, a similar trend was observed in patients with recurrent events compared to those without. Plaques with high stretch concentration and large stretch variation are associated with increased risk of future cerebrovascular events.

Bone Genes in the Kidney of Stone Formers

NASA Astrophysics Data System (ADS)

Evan, Andrew P.; Bledsoe, Sharon B.

2008-09-01

Intraoperative papillary biopsies from kidneys of idiopathic-calcium oxalate stone formers (ICSF) have revealed a distinct pattern of mineral deposition in the interstitium of the renal papilla. The earliest sites of these deposits, termed Randall's plaque, are found in the basement membrane of thin loops of Henle and appear to spread into the surrounding interstitium down to the papillary epithelium. Recent studies show kidney stones of ICSF patients grow attached to the renal papilla and at sites of Randall's plaque. Together these observations suggest that plaque formation may be the critical step in stone formation. In order to control plaque formation and thereby reduce future kidney stone development, the mechanism of plaque deposition must be understood. Because the renal papilla has unique anatomical features similar to bone and the fact that the interstitial deposits of ICSF patients are formed of biological apatite, this paper tests the hypothesis that sites of interstitial plaque form as a result of cell-mediated osteoblast-like activity.

CXCL4 Plasma Levels Are Not Associated with the Extent of Coronary Artery Disease or with Coronary Plaque Morphology

PubMed Central

Erbel, Christian; Korosoglou, Grigorios; Ler, Pearlyn; Akhavanpoor, Mohammadreza; Domschke, Gabriele; Linden, Fabian; Doesch, Andreas O.; Buss, Sebastian J.; Giannitsis, Evangelos; Katus, Hugo A.; Gleissner, Christian A.

2015-01-01

Background CXCL4 is a platelet chemokine released at micromolar concentrations upon platelet activation. CXCL4 has been shown to promote atherogenesis by various mechanisms. However, data on CXCL4 plasma levels in patients with coronary artery disease are largely inconclusive. Computed coronary artery angiography (CCTA) represents an excellent tool to quantify and characterize coronary atherosclerotic plaques. We hypothesized that increased CXCL4 plasma levels may be associated with features of plaque instability resulting in adverse cardiovascular events. Specifically, we sought to determine whether CXCL4 levels are correlated with specific features of coronary artery disease including (1) plaque volume, (2) calcium score, (3) degree of stenosis, or (4) vascular remodeling. Methods and Results CXCL4 plasma levels were measured by ELISA in 217 patients undergoing CCTA for suspected CAD (mean age 64.2 ± 9.4 years, 107 (49.3%) male). Mean CXCL4 plasma levels were 12.5 ± 4.6 ng/mL. There was no significant correlation between CXCL4 levels and any clinical or demographic parameters including cardiovascular risk factors. CXCL4 plasma levels did not differ between patient with or without coronary artery disease (CAD: 12.5 ± 4.5 ng/ml, no CAD: 12.5 ± 4.8 ng/ml). Neither univariate nor multivariate analysis showed an association between CXCL4 levels and plaque volume, total calcium score, degree of stenosis, or vascular remodeling. Subgroup analysis of patients with CAD as confirmed by CCTA did not show any association of CXCL4 levels with the extent of CAD. Conclusions While CXCL4 may be present and active within the arterial wall, local increase of CXCL4 may not translate into systemically elevated CXCL4 levels. Further studies will have to test whether CXCL4 may still represent a suitable therapeutic target in human atherosclerosis. PMID:26524462

CXCL4 Plasma Levels Are Not Associated with the Extent of Coronary Artery Disease or with Coronary Plaque Morphology.

PubMed

Erbel, Christian; Korosoglou, Grigorios; Ler, Pearlyn; Akhavanpoor, Mohammadreza; Domschke, Gabriele; Linden, Fabian; Doesch, Andreas O; Buss, Sebastian J; Giannitsis, Evangelos; Katus, Hugo A; Gleissner, Christian A

2015-01-01

CXCL4 is a platelet chemokine released at micromolar concentrations upon platelet activation. CXCL4 has been shown to promote atherogenesis by various mechanisms. However, data on CXCL4 plasma levels in patients with coronary artery disease are largely inconclusive. Computed coronary artery angiography (CCTA) represents an excellent tool to quantify and characterize coronary atherosclerotic plaques. We hypothesized that increased CXCL4 plasma levels may be associated with features of plaque instability resulting in adverse cardiovascular events. Specifically, we sought to determine whether CXCL4 levels are correlated with specific features of coronary artery disease including (1) plaque volume, (2) calcium score, (3) degree of stenosis, or (4) vascular remodeling. CXCL4 plasma levels were measured by ELISA in 217 patients undergoing CCTA for suspected CAD (mean age 64.2 ± 9.4 years, 107 (49.3%) male). Mean CXCL4 plasma levels were 12.5 ± 4.6 ng/mL. There was no significant correlation between CXCL4 levels and any clinical or demographic parameters including cardiovascular risk factors. CXCL4 plasma levels did not differ between patient with or without coronary artery disease (CAD: 12.5 ± 4.5 ng/ml, no CAD: 12.5 ± 4.8 ng/ml). Neither univariate nor multivariate analysis showed an association between CXCL4 levels and plaque volume, total calcium score, degree of stenosis, or vascular remodeling. Subgroup analysis of patients with CAD as confirmed by CCTA did not show any association of CXCL4 levels with the extent of CAD. While CXCL4 may be present and active within the arterial wall, local increase of CXCL4 may not translate into systemically elevated CXCL4 levels. Further studies will have to test whether CXCL4 may still represent a suitable therapeutic target in human atherosclerosis.

Aggregation and Disaggregation of Senile Plaques in Alzheimer Disease

NASA Astrophysics Data System (ADS)

Cruz, L.; Urbanc, B.; Buldyrev, S. V.; Christie, R.; Gomez-Isla, T.; Havlin, S.; McNamara, M.; Stanley, H. E.; Hyman, B. T.

1997-07-01

We quantitatively analyzed, using laser scanning confocal microscopy, the three-dimensional structure of individual senile plaques in Alzheimer disease. We carried out the quantitative analysis using statistical methods to gain insights about the processes that govern Aβ peptide deposition. Our results show that plaques are complex porous structures with characteristic pore sizes. We interpret plaque morphology in the context of a new dynamical model based on competing aggregation and disaggregation processes in kinetic steady-state equilibrium with an additional diffusion process allowing Aβ deposits to diffuse over the surface of plaques.

Aortic Arch Plaques and Risk of Recurrent Stroke and Death

PubMed Central

Di Tullio, Marco R.; Russo, Cesare; Jin, Zhezhen; Sacco, Ralph L.; Mohr, J.P.; Homma, Shunichi

2010-01-01

Background Aortic arch plaques are a risk factor for ischemic stroke. Although the stroke mechanism is conceivably thromboembolic, no randomized studies have evaluated the efficacy of antithrombotic therapies in preventing recurrent events. Methods and Results The relationship between arch plaques and recurrent events was studied in 516 patients with ischemic stroke, double–blindly randomized to treatment with warfarin or aspirin as part of the Patent Foramen Ovale in Cryptogenic Stroke Study (PICSS), based on the Warfarin-Aspirin Recurrent Stroke Study (WARSS). Plaque thickness and morphology was evaluated by transesophageal echocardiography. End-points were recurrent ischemic stroke or death over a 2-year follow-up. Large plaques (≥4mm) were present in 19.6% of patients, large complex plaques (those with ulcerations or mobile components) in 8.5 %. During follow-up, large plaques were associated with a significantly increased risk of events (adjusted Hazard Ratio 2.12, 95% Confidence Interval 1.04-4.32), especially those with complex morphology (HR 2.55, CI 1.10-5.89). The risk was highest among cryptogenic stroke patients, both for large plaques (HR 6.42, CI 1.62-25.46) and large-complex plaques (HR 9.50, CI 1.92-47.10). Event rates were similar in the warfarin and aspirin groups in the overall study population (16.4% vs. 15.8%; p=0.43). Conclusions In patients with stroke, and especially cryptogenic stroke, large aortic plaques remain associated with an increased risk of recurrent stroke and death at two years despite treatment with warfarin or aspirin. Complex plaque morphology confers a slight additional increase in risk. PMID:19380621

Visualization of Monocytic Cells in Regressing Atherosclerotic Plaques by Intravital 2-Photon and Positron Emission Tomography-Based Imaging-Brief Report.

PubMed

Li, Wenjun; Luehmann, Hannah P; Hsiao, Hsi-Min; Tanaka, Satona; Higashikubo, Ryuji; Gauthier, Jason M; Sultan, Deborah; Lavine, Kory J; Brody, Steven L; Gelman, Andrew E; Gropler, Robert J; Liu, Yongjian; Kreisel, Daniel

2018-05-01

Aortic arch transplants have advanced our understanding of processes that contribute to progression and regression of atherosclerotic plaques. To characterize the dynamic behavior of monocytes and macrophages in atherosclerotic plaques over time, we developed a new model of cervical aortic arch transplantation in mice that is amenable to intravital imaging. Vascularized aortic arch grafts were transplanted heterotropically to the right carotid arteries of recipient mice using microsurgical suture techniques. To image immune cells in atherosclerotic lesions during regression, plaque-bearing aortic arch grafts from B6 ApoE-deficient donors were transplanted into syngeneic CX 3 CR1 GFP reporter mice. Grafts were evaluated histologically, and monocytic cells in atherosclerotic plaques in ApoE-deficient grafts were imaged intravitally by 2-photon microscopy in serial fashion. In complementary experiments, CCR2 + cells in plaques were serially imaged by positron emission tomography using specific molecular probes. Plaques in ApoE-deficient grafts underwent regression after transplantation into normolipidemic hosts. Intravital imaging revealed clusters of largely immotile CX 3 CR1 + monocytes/macrophages in regressing plaques that had been recruited from the periphery. We observed a progressive decrease in CX 3 CR1 + monocytic cells in regressing plaques and a decrease in CCR2 + positron emission tomography signal during 4 months. Cervical transplantation of atherosclerotic mouse aortic arches represents a novel experimental tool to investigate cellular mechanisms that contribute to the remodeling of atherosclerotic plaques. © 2018 American Heart Association, Inc.

The role of microglial cells and astrocytes in fibrillar plaque evolution in transgenic APP(SW) mice.

PubMed

Wegiel, J; Wang, K C; Imaki, H; Rubenstein, R; Wronska, A; Osuchowski, M; Lipinski, W J; Walker, L C; LeVine, H

2001-01-01

Ultrastructural reconstruction of 27 fibrillar plaques in different stages of formation and maturation was undertaken to characterize the development of fibrillar plaques in the brains of human APP(SW) transgenic mice (Tg2576). The study suggests that microglial cells are not engaged in Abeta removal and plaque degradation, but in contrast, are a driving force in plaque formation and development. Fibrillar Abeta deposition at the amyloid pole of microglial cells appears to initiate three types of neuropil response: degeneration of neurons, protective activation of astrocytes, and attraction and activation of microglial cells sustaining plaque growth. Enlargement of neuronal processes and synapses with accumulation of degenerated mitochondria, dense bodies, and Hirano-type bodies is the marker of toxic injury of neurons by fibrillar Abeta. Separation of amyloid cores from neurons and degradation of amyloid cores by cytoplasmic processes of hypertrophic astrocytes suggest the protective and defensive character of astrocytic response to fibrillar Abeta. The growth of cored plaque from a small plaque with one microglial cell with an amyloid star and a few dystrophic neurites to a large plaque formed by several dozen microglial cells seen in old mice is the effect of attraction and activation of microglial cells residing outside of the plaque perimeter. This mechanism of growth of plaques appears to be characteristic of cored plaques in transgenic mice. Other features in mouse microglial cells that are absent in human brain are clusters of vacuoles, probably of lysosomal origin. They evolve into circular cisternae and finally into large vacuoles filled with osmiophilic, amorphous material and bundles of fibrils that are poorly labeled with antibody to Abeta. Microglial cells appear to release large amounts of fibrillar Abeta and accumulate traces of fibrillar Abeta in a lysosomal pathway.

The effect of tooth brushing and flossing sequence on interdental plaque reduction and fluoride retention: A randomized controlled clinical trial.

PubMed

Mazhari, Fatemeh; Boskabady, Marzie; Moeintaghavi, Amir; Habibi, Atieh

2018-05-09

Mechanical plaque control methods such as brushing and flossing are highly recommended to remove dental plaque. The aim of this study is to evaluate the efficacy of the sequence of brushing and flossing on reducing interdental plaque and increasing fluoride retention in that area. This randomized controlled crossover trial was conducted on 25 dental students. After prophylaxis, they were asked to discontinue all forms of oral hygiene for 48 hours. The study was performed in two phases with two-week washout intervals. In one phase, they first brushed, then flossed (sequence 1: brush-floss group). In the other phase they initially used dental floss then brushed (sequence 2: floss-brush group). At each phase, dental plaque (using the Rustogi Modified Navy Plaque Index) and fluoride concentrations (using a fluoride ion specific electrode) were measured before and after flossing and brushing, and the dental plaque reduction and fluoride increase were compared between the two groups using the mixed model test. A significance level of 5% was selected. In the floss-brush group interdental and whole plaque was reduced significantly more than the brush-floss group (p = 0.001, p = 0.009 respectively). However, marginal plaque did not show any statistically significant difference between the two groups (p = 0.2). Fluoride concentrations in interdental plaque were significantly higher in the floss-brush group than the other group (p = 0.027). The results showed that flossing followed by brushing is preferred to brushing then flossing in order to reduce interdental plaque and increase fluoride concentration in interdental plaque. This article is protected by copyright. All rights reserved. © 2018 American Academy of Periodontology.

Dental plaque as a biofilm and a microbial community – implications for health and disease

PubMed Central

Marsh, Philip D

2006-01-01

Dental plaque is a structurally- and functionally-organized biofilm. Plaque forms in an ordered way and has a diverse microbial composition that, in health, remains relatively stable over time (microbial homeostasis). The predominant species from diseased sites are different from those found in healthy sites, although the putative pathogens can often be detected in low numbers at normal sites. In dental caries, there is a shift toward community dominance by acidogenic and acid-tolerating species such as mutans streptococci and lactobacilli, although other species with relevant traits may be involved. Strategies to control caries could include inhibition of biofilm development (e.g. prevention of attachment of cariogenic bacteria, manipulation of cell signaling mechanisms, delivery of effective antimicrobials, etc.), or enhancement of the host defenses. Additionally, these more conventional approaches could be augmented by interference with the factors that enable the cariogenic bacteria to escape from the normal homeostatic mechanisms that restrict their growth in plaque and out compete the organisms associated with health. Evidence suggests that regular conditions of low pH in plaque select for mutans streptococci and lactobacilli. Therefore, the suppression of sugar catabolism and acid production by the use of metabolic inhibitors and non-fermentable artificial sweeteners in snacks, or the stimulation of saliva flow, could assist in the maintenance of homeostasis in plaque. Arguments will be presented that an appreciation of ecological principles will enable a more holistic approach to be taken in caries control. PMID:16934115

MRI-based biomechanical parameters for carotid artery plaque vulnerability assessment.

PubMed

Speelman, Lambert; Teng, Zhongzhao; Nederveen, Aart J; van der Lugt, Aad; Gillard, Jonathan H

2016-03-01

Carotid atherosclerotic plaques are a major cause of ischaemic stroke. The biomechanical environment to which the arterial wall and plaque is subjected to plays an important role in the initiation, progression and rupture of carotid plaques. MRI is frequently used to characterize the morphology of a carotid plaque, but new developments in MRI enable more functional assessment of carotid plaques. In this review, MRI based biomechanical parameters are evaluated on their current status, clinical applicability, and future developments. Blood flow related biomechanical parameters, including endothelial wall shear stress and oscillatory shear index, have been shown to be related to plaque formation. Deriving these parameters directly from MRI flow measurements is feasible and has great potential for future carotid plaque development prediction. Blood pressure induced stresses in a plaque may exceed the tissue strength, potentially leading to plaque rupture. Multi-contrast MRI based stress calculations in combination with tissue strength assessment based on MRI inflammation imaging may provide a plaque stress-strength balance that can be used to assess the plaque rupture risk potential. Direct plaque strain analysis based on dynamic MRI is already able to identify local plaque displacement during the cardiac cycle. However, clinical evidence linking MRI strain to plaque vulnerability is still lacking. MRI based biomechanical parameters may lead to improved assessment of carotid plaque development and rupture risk. However, better MRI systems and faster sequences are required to improve the spatial and temporal resolution, as well as increase the image contrast and signal-to-noise ratio.

The influence of composition and location on the toughness of human atherosclerotic femoral plaque tissue.

PubMed

Cunnane, E M; Barrett, H E; Kavanagh, E G; Mongrain, R; Walsh, M T

2016-02-01

The toughness of femoral atherosclerotic tissue is of pivotal importance to understanding the mechanism of luminal expansion during cutting balloon angioplasty (CBA) in the peripheral vessels. Furthermore, the ability to relate this parameter to plaque composition, pathological inclusions and location within the femoral vessels would allow for the improvement of existing CBA technology and for the stratification of patient treatment based on the predicted fracture response of the plaque tissue to CBA. Such information may lead to a reduction in clinically observed complications, an improvement in trial results and an increased adoption of the CBA technique to reduce vessel trauma and further endovascular treatment uptake. This study characterises the toughness of atherosclerotic plaque extracted from the femoral arteries of ten patients using a lubricated guillotine cutting test to determine the critical energy release rate. This information is related to the location that the plaque section was removed from within the femoral vessels and the composition of the plaque tissue, determined using Fourier Transform InfraRed spectroscopy, to establish the influence of location and composition on the toughness of the plaque tissue. Scanning electron microscopy (SEM) is employed to examine the fracture surfaces of the sections to determine the contribution of tissue morphology to toughness. Toughness results exhibit large inter and intra patient and location variance with values ranging far above and below the toughness of healthy porcine arterial tissue (Range: 1330-3035 for location and 140-4560J/m(2) for patients). No significant difference in mean toughness is observed between patients or location. However, the composition parameter representing the calcified tissue content of the plaque correlates significantly with sample toughness (r=0.949, p<0.001). SEM reveals the presence of large calcified regions in the toughest sections that are absent from the least tough sections. Regression analysis highlights the potential of employing the calcified tissue content of the plaque as a preoperative tool for predicting the fracture response of a target lesion to CBA (R(2)=0.885, p<0.001). This study addresses a gap in current knowledge regarding the influence of plaque location, composition and morphology on the toughness of human femoral plaque tissue. Such information is of great importance to the continued improvement of endovascular treatments, particularly cutting balloon angioplasty (CBA), which require experimentally derived data as a framework for assessing clinical cases and advancing medical devices. This study identifies that femoral plaque tissue exhibits large inter and intra patient and location variance regarding tissue toughness. Increasing calcified plaque content is demonstrated to correlate significantly with increasing toughness. This highlights the potential for predicting target lesion toughness which may lead to an increased adoption of the CBA technique and also further the uptake of endovascular treatment. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Molecular Phenotyping Small (Asian) versus Large (Western) Plaque Psoriasis Shows Common Activation of IL-17 Pathway Genes, but Different Regulatory Gene Sets

PubMed Central

Kim, Jaehwan; Oh, Chil-Hwan; Jeon, Jiehyun; Baek, Yoosang; Ahn, Jaewoo; Kim, Dong Joo; Lee, Hyun-Soo; da Rosa, Joel Correa; Suárez-Fariñas, Mayte; Lowes, Michelle A.; Krueger, James G.

2015-01-01

Psoriasis is present in all racial groups, but in varying frequencies and severity. Considering that small plaque psoriasis is specific to the Asian population and severe psoriasis is more predominant in the Western population, we defined Asian small and intermediate plaque psoriasis as psoriasis subtypes, and compared their molecular signatures with classic subtype of Western large plaque psoriasis. Two different characteristics of psoriatic spreading—vertical growth and radial expansion—were contrasted between subtypes, and genomic data were correlated to histologic and clinical measurements. Compared to Western large plaque psoriasis, Asian small plaque psoriasis revealed limited psoriasis spreading, but IL-17A and IL-17-regulated pro-inflammatory cytokines were highly expressed. Paradoxically, IL-17A and IL-17-regulated pro-inflammatory cytokines were lower in Western large plaque psoriasis, while T cells and dendritic cells in total psoriatic skin area were exponentially increased. Negative immune regulators, such as CD69 and FAS, were decreased in both Western large plaque psoriasis and psoriasis with accompanying arthritis or obesity, and their expression was correlated with psoriasis severity index. Based on the disease subtype comparisons, we propose that dysregulation of T cell expansion enabled by downregulation of immune negative regulators is the main mechanism for development of large plaque psoriasis subtypes. PMID:26763436

Endothelial glycocalyx, apoptosis and inflammation in an atherosclerotic mouse model

PubMed Central

Mensah, Solomon; Hirshberg, Carly; Tarbell, John M.

2016-01-01

Background and aims Previous experiments suggest that both increased endothelial cell apoptosis and endothelial surface glycocalyx shedding could play a role in the endothelial dysfunction and inflammation of athero-prone regions of the vasculature. We sought to elucidate the possibly synergistic mechanisms by which endothelial cell apoptosis and glycocalyx shedding promote atherogenesis. Methods 4- to 6-week old male C57Bl/6 apolipoprotein E knockout (ApoE−/−) mice were fed a Western diet for 10 weeks and developed plaques in their brachiocephalic arteries. Results Glycocalyx coverage and thickness were significantly reduced over the plaque region compared to the non-plaque region (coverage plaque: 71±23%, non-plaque: 97±3%, p= 0.02; thickness plaque: 0.85±0.15 μm, non-plaque: 1.2±0.21 μm, p= 0.006). Values in the non-plaque region were not different from those found in wild type mice fed a normal diet (coverage WT: 92±3%, p= 0.7 vs. non-plaque ApoE−/−, thickness WT: 1.1±0.06 μm, p= 0.2 vs. non-plaque ApoE−/−). Endothelial cell apoptosis was significantly increased in ApoE−/− mice compared to wild type mice (ApoE−/− :64.3±33.0, WT: 1.1±0.5 TUNEL-pos/cm, p= 2×10−7). The number of apoptotic endothelial cells per unit length was 2 times higher in the plaque region than in the non-plaque region of the same vessel (p= 3×10−5). Increased expression of matrix metalloproteinase 9 co-localized with glycocalyx shedding and plaque buildup. Conclusions Our results suggest that, in concert with endothelial apoptosis that increases lipid permeability, glycocalyx shedding initiated by inflammation facilitates monocyte adhesion and macrophage infiltration that promote lipid retention and the development of atherosclerotic plaques. PMID:27529818

Comparison by optical coherence tomography of the frequency of lipid coronary plaques in current smokers, former smokers, and nonsmokers.

PubMed

Abtahian, Farhad; Yonetsu, Taishi; Kato, Koji; Jia, Haibo; Vergallo, Rocco; Tian, Jinwei; Hu, Sining; McNulty, Iris; Lee, Hang; Yu, Bo; Jang, Ik-Kyung

2014-09-01

Smoking is associated with high incidence of cardiovascular events including acute coronary syndrome. We sought to characterize coronary plaques in patients with ongoing smoking using optical coherence tomography (OCT) compared with former smokers and nonsmokers. We identified 465 coronary plaques from 182 subjects who underwent OCT imaging for all 3 coronary arteries. Subjects were divided into 3 groups: current smokers (n = 41), former smokers (n = 67), and nonsmokers (n = 74). OCT analysis included the presence of lipid-rich plaque, thin-cap fibroatheroma (TCFA), calcification, maximum lipid arc, lipid core length, lipid index, and fibrous cap thickness. Lipid index was defined by mean lipid arc multiplied by lipid core length. Compared with former smokers and nonsmokers, the incidence of lipid plaques and TCFA was significantly higher in current smokers (lipid plaques: 68.0% vs 45.9% and 52.6%, p = 0.002; TCFA: 18.4% vs 7.6% and 9.9%, p = 0.018). There was a trend for higher plaque disruption in current smokers. Former smokers were more likely to have calcified plaques than current and nonsmokers (52.9% vs 32.0% and 38.0%, p = 0.001). In a multivariate analysis, current smoking, low-density lipoprotein, and presentation with acute coronary syndrome were independently associated with the presence of TCFAs. In conclusion, current smokers are more likely to have lipid plaques and OCT-defined vulnerable plaques (TCFAs). Former smokers have increased number of calcified plaques. These results may explain the increased risk of acute cardiac events among smokers. Copyright © 2014 Elsevier Inc. All rights reserved.

Local Non-Esterified Fatty Acids Correlate With Inflammation in Atheroma Plaques of Patients With Type 2 Diabetes

PubMed Central

Mas, Sebastián; Martínez-Pinna, Roxana; Martín-Ventura, Jose Luis; Pérez, Raul; Gomez-Garre, Dulcenombre; Ortiz, Alberto; Fernandez-Cruz, Arturo; Vivanco, Fernando; Egido, Jesús

2010-01-01

OBJECTIVE Atherosclerosis is prevalent in diabetic patients, but there is little information on the localization of nonesterified fatty acids (NEFAs) within the plaque and their relationship with inflammation. We sought to characterize the NEFA composition and location in human diabetic atheroma plaques by metabolomic analysis and imaging and to address their relationship with inflammation activity. RESEARCH DESIGN AND METHODS Time-of-flight secondary ion mass spectrometry (TOF-SIMS) was used for metabolomic analysis imaging of frozen carotid atheroma plaques. Carotid endarterectomy specimens were used for conventional immunohistochemistry, laser-capture microdissection quantitative PCR, and in situ Southwestern hybridization. Biological actions of linoleic acid were studied in cultured vascular smooth muscle cells (VSMCs). RESULTS TOF-SIMS imaging evidenced a significant increase in the quantity of several NEFA in diabetic versus nondiabetic atheroma plaques. Higher levels of NEFA were also found in diabetic sera. The presence of LPL mRNA in NEFA-rich areas of the atheroma plaque, as well as the lack of correlation between serum and plaque NEFA, suggests a local origin for plaque NEFA. The pattern of distribution of plaque NEFA is similar to that of MCP-1, LPL, and activated NF-κB. Diabetic endarterectomy specimens showed higher numbers of infiltrating macrophages and T-lymphocytes—a finding that associated with higher NEFA levels. Finally, linoleic acid activates NF-κB and upregulates NF-κB–mediated LPL and MCP-1 expression in cultured VSMC. DISCUSSION There is an increased presence of NEFA in diabetic plaque neointima. NEFA levels are higher in diabetic atheroma plaques than in nondiabetic subjects. We hypothesize that NEFA may be produced locally and contribute to local inflammation. PMID:20200316

Differences in coronary plaque composition with aging measured by coronary computed tomography angiography.

PubMed

Tota-Maharaj, Rajesh; Blaha, Michael J; Rivera, Juan J; Henry, Travis S; Choi, Eue-Keun; Chang, Sung-A; Yoon, Yeonyee E; Chun, Eun Ju; Choi, Sang-Il; Blumenthal, Roger S; Chang, Hyuk-Jae; Nasir, Khurram

2012-07-12

Little is known about the independent impact of aging on coronary plaque morphology and composition in the era of cardiac computed tomography angiography (CCTA). We studied 1015 consecutive asymptomatic South Korean subjects (49 ± 10 years, 64% men) who underwent 64-slice CCTA during routine health evaluation. Coronary plaque characteristics were analyzed on a per-segment basis according to the modified AHA classification. Plaques with >50% calcified tissue were classified as calcified (CAP), plaques with <50% calcified tissue were classified as mixed (MCAP), and plaques without calcium were classified as non-calcified (NCAP). Multiple regression analysis was employed to describe the cross-sectional association between age tertile and plaque type burden (≥ 2 affected segments) after adjustment for other cardiovascular risk factors. The prevalence of coronary plaque increased with age, (1st tertile: 7.5%, 3rd tertile: 38.5% [p<0.001]). The relative contribution of NCAP to overall plaque burden decreased with age from nearly 50% in the first tertile to approximately 20% in the third, while there was a reciprocal increase in both MCAP and CAP subtypes. In multivariable analysis, patients in the oldest tertile had a 2.5-fold increase in burden of NCAP, yet a nearly 40-fold increase in MCAP and 16-fold increase in CAP compared to the youngest tertile. In conclusion, CCTA is an effective method for measuring age-related differences in the burden of individual coronary plaque subtypes. Future research is needed to determine whether the increase in mixed and calcified plaques seen with aging produce an independent contribution to the age-related increase in cardiovascular risk. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Immunohistological Analysis of Intracoronary Thrombus Aspirate in STEMI Patients: Clinical Implications of Pathological Findings.

PubMed

Blasco, Ana; Bellas, Carmen; Goicolea, Leyre; Muñiz, Ana; Abraira, Víctor; Royuela, Ana; Mingo, Susana; Oteo, Juan Francisco; García-Touchard, Arturo; Goicolea, Francisco Javier

2017-03-01

Thrombus aspiration allows analysis of intracoronary material in patients with ST-segment elevation myocardial infarction. Our objective was to characterize this material by immunohistology and to study its possible association with patient progress. This study analyzed a prospective cohort of 142 patients undergoing primary angioplasty with positive coronary aspiration. Histological examination of aspirated samples included immunohistochemistry stains for the detection of plaque fragments. The statistical analysis comprised histological variables (thrombus age, degree of inflammation, presence of plaque), the patients' clinical and angiographic features, estimation of survival curves, and logistic regression analysis. Among the histological markers, only the presence of plaque (63% of samples) was associated with postinfarction clinical events. Factors associated with 5-year event-free survival were the presence of plaque in the aspirate (82.2% vs 66.0%; P = .033), smoking (82.5% smokers vs 66.7% nonsmokers; P = .036), culprit coronary artery (83.3% circumflex or right coronary artery vs 68.5% anterior descending artery; P = .042), final angiographic flow (80.8% II-III vs 30.0% 0-I; P < .001) and left ventricular ejection fraction ≥ 35% at discharge (83.7% vs 26.7%; P < .001). On multivariable Cox regression analysis with these variables, independent predictors of event-free survival were the presence of plaque (hazard ratio, 0.37; 95%CI, 0.18-0.77; P = .008), and left ventricular ejection fraction (hazard ratio, 0.92; 95%CI, 0.88-0.95; P < .001). The presence of plaque in the coronary aspirate of patients with ST elevation myocardial infarction may be an independent prognostic marker. CD68 immunohistochemical stain is a good method for plaque detection. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Quantification of plaque area and characterization of plaque biochemical composition with atherosclerosis progression in ApoE/LDLR(-/-) mice by FT-IR imaging.

PubMed

Wrobel, Tomasz P; Mateuszuk, Lukasz; Kostogrys, Renata B; Chlopicki, Stefan; Baranska, Malgorzata

2013-11-07

In this work the quantitative determination of atherosclerotic lesion area (ApoE/LDLR(-/-) mice) by FT-IR imaging is presented and validated by comparison with atherosclerotic lesion area determination by classic Oil Red O staining. Cluster analysis of FT-IR-based measurements in the 2800-3025 cm(-1) range allowed for quantitative analysis of the atherosclerosis plaque area, the results of which were highly correlated with those of Oil Red O histological staining (R(2) = 0.935). Moreover, a specific class obtained from a second cluster analysis of the aortic cross-section samples at different stages of disease progression (3, 4 and 6 months old) seemed to represent the macrophages (CD68) area within the atherosclerotic plaque.

Effectiveness of Azadirachta indica (neem) mouthrinse in plaque and gingivitis control: a systematic review.

PubMed

Dhingra, K; Vandana, K L

2017-02-01

The aim of this systematic review was to evaluate the effectiveness of Azadirachta indica (neem)-based herbal mouthrinse in improving plaque control and gingival health. Literature search was accomplished using electronic databases (PubMed, Cochrane Central Register of Controlled Trials and EMBASE) and manual searching, up to February 2015, for randomized controlled trials (RCTs) presenting clinical data for efficacy of neem mouthrinses when used alone or as an adjunct to mechanical oral hygiene as compared to chlorhexidine mouthrinses for controlling plaque and gingival inflammation in patients with gingivitis. Of the total 206 articles searched, three randomized controlled trials evaluating neem-based herbal mouthrinses were included. Due to marked heterogeneity observed in study characteristics, meta-analysis was not performed. These studies reported that neem mouthrinse was as effective as chlorhexidine mouthrinse when used as an adjunct to toothbrushing in reducing plaque and gingival inflammation in gingivitis patients. However, the quality of reporting and evidence along with methods of studies was generally flawed with unclear risk of bias. Despite the promising results shown in existing randomized controlled trials, the evidence concerning the clinical use of neem mouthrinses is lacking and needs further reinforcement with high-quality randomized controlled trials based on the reporting guidelines of herbal CONSORT statement. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Painting blood vessels and atherosclerotic plaques with an adhesive drug depot

PubMed Central

Kastrup, Christian J.; Nahrendorf, Matthias; Figueiredo, Jose Luiz; Lee, Haeshin; Kambhampati, Swetha; Lee, Timothy; Cho, Seung-Woo; Gorbatov, Rostic; Iwamoto, Yoshiko; Dang, Tram T.; Dutta, Partha; Yeon, Ju Hun; Cheng, Hao; Pritchard, Christopher D.; Vegas, Arturo J.; Siegel, Cory D.; MacDougall, Samantha; Okonkwo, Michael; Thai, Anh; Stone, James R.; Coury, Arthur J.; Weissleder, Ralph; Langer, Robert; Anderson, Daniel G.

2012-01-01

The treatment of diseased vasculature remains challenging, in part because of the difficulty in implanting drug-eluting devices without subjecting vessels to damaging mechanical forces. Implanting materials using adhesive forces could overcome this challenge, but materials have previously not been shown to durably adhere to intact endothelium under blood flow. Marine mussels secrete strong underwater adhesives that have been mimicked in synthetic systems. Here we develop a drug-eluting bioadhesive gel that can be locally and durably glued onto the inside surface of blood vessels. In a mouse model of atherosclerosis, inflamed plaques treated with steroid-eluting adhesive gels had reduced macrophage content and developed protective fibrous caps covering the plaque core. Treatment also lowered plasma cytokine levels and biomarkers of inflammation in the plaque. The drug-eluting devices developed here provide a general strategy for implanting therapeutics in the vasculature using adhesive forces and could potentially be used to stabilize rupture-prone plaques. PMID:23236189

Genesis and growth of extracellular vesicle-derived microcalcification in atherosclerotic plaques

PubMed Central

Hutcheson, Joshua D.; Goettsch, Claudia; Bertazzo, Sergio; Maldonado, Natalia; Ruiz, Jessica L.; Goh, Wilson; Yabusaki, Katsumi; Faits, Tyler; Bouten, Carlijn; Franck, Gregory; Quillard, Thibaut; Libby, Peter; Aikawa, Masanori; Weinbaum, Sheldon; Aikawa, Elena

2015-01-01

Clinical evidence links arterial calcification and cardiovascular risk. Finite-element modelling of the stress distribution within atherosclerotic plaques has suggested that subcellular microcalcifications in the fibrous cap may promote material failure of the plaque, but that large calcifications can stabilize it. Yet the physicochemical mechanisms underlying such mineral formation and growth in atheromata remain unknown. Here, by using three-dimensional collagen hydrogels that mimic structural features of the atherosclerotic fibrous cap, and high-resolution microscopic and spectroscopic analyses of both the hydrogels and of calcified human plaques, we demonstrate that calcific mineral formation and maturation results from a series of events involving the aggregation of calcifying extracellular vesicles, and the formation of microcalcifications and ultimately large calcification zones. We also show that calcification morphology and the plaque’s collagen content – two determinants of atherosclerotic plaque stability - are interlinked. PMID:26752654

Computational Fluid Dynamics Analysis of the Effect of Plaques in the Left Coronary Artery

PubMed Central

Chaichana, Thanapong; Sun, Zhonghua; Jewkes, James

2012-01-01

This study was to investigate the hemodynamic effect of simulated plaques in left coronary artery models, which were generated from a sample patient's data. Plaques were simulated and placed at the left main stem and the left anterior descending (LAD) to produce at least 60% coronary stenosis. Computational fluid dynamics analysis was performed to simulate realistic physiological conditions that reflect the in vivo cardiac hemodynamics, and comparison of wall shear stress (WSS) between Newtonian and non-Newtonian fluid models was performed. The pressure gradient (PSG) and flow velocities in the left coronary artery were measured and compared in the left coronary models with and without presence of plaques during cardiac cycle. Our results showed that the highest PSG was observed in stenotic regions caused by the plaques. Low flow velocity areas were found at postplaque locations in the left circumflex, LAD, and bifurcation. WSS at the stenotic locations was similar between the non-Newtonian and Newtonian models although some more details were observed with non-Newtonian model. There is a direct correlation between coronary plaques and subsequent hemodynamic changes, based on the simulation of plaques in the realistic coronary models. PMID:22400051

A comparison of Listerine® and sodium bicarbonate oral cleansing solutions on dental plaque colonisation and incidence of ventilator associated pneumonia in mechanically ventilated patients: a randomised control trial.

PubMed

Berry, A M

2013-10-01

Effective oral hygiene has been proposed as a key factor in the reduction of dental plaque colonisation and subsequent development of ventilator associated pneumonia (VAP). Listerine(®) oral rinse, while used extensively in dental practice has rarely been tested in mechanically ventilated patients. Sodium bicarbonate as an oral rinse has been more commonly utilised in oral hygiene regimens in intensive care patients. To test the efficacies of the essential oil mouth rinse, Listerine(®) (Pfizer) and sodium bicarbonate in the reduction of dental plaque colonisation with respiratory pathogens and the subsequent development of VAP. The study design was a prospective, single blind randomised comparative study of adult patients mechanically ventilated for at least 4 days. Patients were randomised to Listerine(®) (Pfizer) oral rinse twice daily, sodium bicarbonate oral rinse 2/24 or sterile water 2/24 (control group). All groups received tooth brushing 3 times a day. Dental plaque colonisation (primary outcome) and incidence of ventilator associated pneumonia (secondary outcome) were studied. Three hundred and ninety-eight patients were randomised to either the Listerine group (127), sodium bicarbonate group (133) or the control group (138). Baseline characteristics were similar for all groups. There were no significant differences between the control and study groups in colonisation of dental plaque at Day 4 (p=0.243). Ventilator associated pneumonia was diagnosed in 18 patients. The incidence was, Listerine(®) group 4.7%, sodium bicarbonate group 4.5% and control 4.3% [OR, 0.99; 95% CI, 0.31 to 3.16; p=0.92]. Compared to the control group, Listerine(®) or sodium bicarbonate oral rinses were not more effective in the reduction of colonisation of dental plaque or the incidence of VAP. Given the low incidence of VAP, the common factor of a small, soft toothbrush as part of an oral hygiene regimen suggests possible benefit in mechanically ventilated patients. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Linkages between oral commensal bacteria and atherosclerotic plaques in coronary artery disease patients.

PubMed

Chhibber-Goel, Jyoti; Singhal, Varsha; Bhowmik, Debaleena; Vivek, Rahul; Parakh, Neeraj; Bhargava, Balram; Sharma, Amit

2016-01-01

Coronary artery disease is an inflammatory disorder characterized by narrowing of coronary arteries due to atherosclerotic plaque formation. To date, the accumulated epidemiological evidence supports an association between oral bacterial diseases and coronary artery disease, but has failed to prove a causal link between the two. Due to the recent surge in microbial identification and analyses techniques, a number of bacteria have been independently found in atherosclerotic plaque samples from coronary artery disease patients. In this study, we present meta-analysis from published studies that have independently investigated the presence of bacteria within atherosclerotic plaque samples in coronary artery disease patients. Data were collated from 63 studies covering 1791 patients spread over a decade. Our analysis confirms the presence of 23 oral commensal bacteria, either individually or in co-existence, within atherosclerotic plaques in patients undergoing carotid endarterectomy, catheter-based atherectomy, or similar procedures. Of these 23 bacteria, 5 ( Campylobacter rectus , Porphyromonas gingivalis , Porphyromonas endodontalis , Prevotella intermedia , Prevotella nigrescens ) are unique to coronary plaques, while the other 18 are additionally present in non-cardiac organs, and associate with over 30 non-cardiac disorders. We have cataloged the wide spectrum of proteins secreted by above atherosclerotic plaque-associated bacteria, and discuss their possible roles during microbial migration via the bloodstream. We also highlight the prevalence of specific poly-microbial communities within atherosclerotic plaques. This work provides a resource whose immediate implication is the necessity to systematically catalog landscapes of atherosclerotic plaque-associated oral commensal bacteria in human patient populations.

Effect of the presence of dental plaque on oral sugar clearance and salivary pH: an in vivo study.

PubMed

Pradhan, Debapriya; Jain, Deepak; Gulati, Amit; Kolhe, Swapnil J; Baad, Rajendra; Rao, B Sunil

2012-11-01

Fermentable carbohydrates and microorganisms in the plaque play a significant role in the pathogenesis of dental caries. Oral clearance of sugars and salivary pH is affected by the presence of plaque. This study was conducted to study the effect of the presence of plaque on the salivary clearance of sucrose and on salivary pH. The study design was of a randomized controlled parallel group clinical trial and included two groups: The control group and plaque group, as follows: Control group--subjects without plaque and plaque group--subjects with plaque. Salivary sucrose determination was done by using the anthrone technique. A digital pH meter estimated the salivary pH. The Student's t test and Mann-Whitney test was employed to compare the intergroup differences. Pearson's correlation coefficient was used for analysis. The salivary sucrose clearance time was increased by presence of plaque. The presence of plaque led to increased salivary sucrose concentrations and increased the salivary sucrose clearance time. The dental caries is the dynamic relationship among the dental plaque microbiota, dietary carbohydrates, saliva and cariogenic potential of the dental plaque. Caries occur preferentially in the dentition sites characterized by high exposure to carbohydrate and diminished salivary effect.

Keeping an eye on the ring: COMS plaque loading optimization for improved dose conformity and homogeneity.

PubMed

Gagne, Nolan L; Cutright, Daniel R; Rivard, Mark J

2012-09-01

To improve tumor dose conformity and homogeneity for COMS plaque brachytherapy by investigating the dosimetric effects of varying component source ring radionuclides and source strengths. The MCNP5 Monte Carlo (MC) radiation transport code was used to simulate plaque heterogeneity-corrected dose distributions for individually-activated source rings of 14, 16 and 18 mm diameter COMS plaques, populated with (103)Pd, (125)I and (131)Cs sources. Ellipsoidal tumors were contoured for each plaque size and MATLAB programming was developed to generate tumor dose distributions for all possible ring weighting and radionuclide permutations for a given plaque size and source strength resolution, assuming a 75 Gy apical prescription dose. These dose distributions were analyzed for conformity and homogeneity and compared to reference dose distributions from uniformly-loaded (125)I plaques. The most conformal and homogeneous dose distributions were reproduced within a reference eye environment to assess organ-at-risk (OAR) doses in the Pinnacle(3) treatment planning system (TPS). The gamma-index analysis method was used to quantitatively compare MC and TPS-generated dose distributions. Concentrating > 97% of the total source strength in a single or pair of central (103)Pd seeds produced the most conformal dose distributions, with tumor basal doses a factor of 2-3 higher and OAR doses a factor of 2-3 lower than those of corresponding uniformly-loaded (125)I plaques. Concentrating 82-86% of the total source strength in peripherally-loaded (131)Cs seeds produced the most homogeneous dose distributions, with tumor basal doses 17-25% lower and OAR doses typically 20% higher than those of corresponding uniformly-loaded (125)I plaques. Gamma-index analysis found > 99% agreement between MC and TPS dose distributions. A method was developed to select intra-plaque ring radionuclide compositions and source strengths to deliver more conformal and homogeneous tumor dose distributions than uniformly-loaded (125)I plaques. This method may support coordinated investigations of an appropriate clinical target for eye plaque brachytherapy.

Strategic Protein Target Analysis for Developing Drugs to Stop Dental Caries

PubMed Central

Horst, J.A.; Pieper, U.; Sali, A.; Zhan, L.; Chopra, G.; Samudrala, R.; Featherstone, J.D.B.

2012-01-01

Dental caries is the most common disease to cause irreversible damage in humans. Several therapeutic agents are available to treat or prevent dental caries, but none besides fluoride has significantly influenced the disease burden globally. Etiologic mechanisms of the mutans group streptococci and specific Lactobacillus species have been characterized to various degrees of detail, from identification of physiologic processes to specific proteins. Here, we analyze the entire Streptococcus mutans proteome for potential drug targets by investigating their uniqueness with respect to non-cariogenic dental plaque bacteria, quality of protein structure models, and the likelihood of finding a drug for the active site. Our results suggest specific targets for rational drug discovery, including 15 known virulence factors, 16 proteins for which crystallographic structures are available, and 84 previously uncharacterized proteins, with various levels of similarity to homologs in dental plaque bacteria. This analysis provides a map to streamline the process of clinical development of effective multispecies pharmacologic interventions for dental caries. PMID:22899687

C-reactive protein in atherosclerosis - A risk marker but not a causal factor? A 13-year population-based longitudinal study: The Tromsø study.

PubMed

Eltoft, Agnethe; Arntzen, Kjell Arne; Hansen, John-Bjarne; Wilsgaard, Tom; Mathiesen, Ellisiv B; Johnsen, Stein Harald

2017-08-01

CRP predicts cardiovascular disease (CVD) in large epidemiologic studies. The aim of the present study was to elucidate the role of CRP in atherosclerosis formation and progression in a prospective population-based study. 6503 middle-aged subjects from The Tromsø study had serum CRP, carotid ultrasound and complete covariate data collected at baseline in 1994. Of these, 4730 and 2917 attended follow-up surveys with repeated assessments in 2001 and 2007, respectively. The cross-sectional associations between CRP and subclinical carotid atherosclerosis, and the longitudinal associations between baseline CRP and novel plaque formation and plaque progression were assessed in generalized estimating equations and linear mixed models stratified by sex. At baseline, traditional risk factors and plaque prevalence increased by CRP risk categories (<1 mg/L, 1-3 mg/L, and >3 mg/L) in both sexes. In cross-sectional analyses, multivariable-adjusted CRP was associated with plaque prevalence and total plaque area (TPA) in men and women. Age-adjusted baseline CRP >3 mg/L compared to CRP <1 mg/L predicted novel plaque formation (OR 1.44, CI 1.08-1.92) and TPA progression (β = 0.0.029 (CI, 0.003-0.056)) in men, but not in women. In neither men nor women was baseline CRP a predictor of TPA-progression or novel plaque formation when adjusted for traditional risk factors. CRP was associated with plaque presence and TPA in cross-sectional analyses, but was not an independent predictor of novel plaque formation or plaque progression. Our findings suggest that CRP may link to CVD by other mechanisms than promoting formation and progression of atherosclerotic plaques. Copyright © 2017 Elsevier B.V. All rights reserved.

Ultrasound Tissue Characterization of Vulnerable Atherosclerotic Plaque

PubMed Central

Picano, Eugenio; Paterni, Marco

2015-01-01

A thrombotic occlusion of the vessel fed by ruptured coronary atherosclerotic plaque may result in unstable angina, myocardial infarction or death, whereas embolization from a plaque in carotid arteries may result in transient ischemic attack or stroke. The atherosclerotic plaque prone to such clinical events is termed high-risk or vulnerable plaque, and its identification in humans before it becomes symptomatic has been elusive to date. Ultrasonic tissue characterization of the atherosclerotic plaque is possible with different techniques—such as vascular, transesophageal, and intravascular ultrasound—on a variety of arterial segments, including carotid, aorta, and coronary districts. The image analysis can be based on visual, video-densitometric or radiofrequency methods and identifies three distinct textural patterns: hypo-echoic (corresponding to lipid- and hemorrhage-rich plaque), iso- or moderately hyper-echoic (fibrotic or fibro-fatty plaque), and markedly hyperechoic with shadowing (calcific plaque). Hypoechoic or dishomogeneous plaques, with spotty microcalcification and large plaque burden, with plaque neovascularization and surface irregularities by contrast-enhanced ultrasound, are more prone to clinical complications than hyperechoic, extensively calcified, homogeneous plaques with limited plaque burden, smooth luminal plaque surface and absence of neovascularization. Plaque ultrasound morphology is important, along with plaque geometry, in determining the atherosclerotic prognostic burden in the individual patient. New quantitative methods beyond backscatter (to include speed of sound, attenuation, strain, temperature, and high order statistics) are under development to evaluate vascular tissues. Although not yet ready for widespread clinical use, tissue characterization is listed by the American Society of Echocardiography roadmap to 2020 as one of the most promising fields of application in cardiovascular ultrasound imaging, offering unique opportunities for the early detection and treatment of atherosclerotic disease. PMID:25950760

Distinguishing characteristics of idiopathic calcium oxalate kidney stone formers with low amounts of Randall's plaque.

PubMed

Wang, Xiangling; Krambeck, Amy E; Williams, James C; Tang, Xiaojing; Rule, Andrew D; Zhao, Fang; Bergstralh, Eric; Haskic, Zejfa; Edeh, Samuel; Holmes, David R; Herrera Hernandez, Loren P; Lieske, John C

2014-10-07

Overgrowth of calcium oxalate on Randall's plaque is a mechanism of stone formation among idiopathic calcium oxalate stone-formers (ICSFs). It is less clear how stones form when there is little or no plaque. Participants were a consecutive cohort of ICSFs who underwent percutaneous nephroscopic papillary mapping in the kidney or kidneys containing symptomatic stones and a papillary tip biopsy from a representative calyx during a stone removal procedure between 2009 and 2013. The distribution of Randall's plaque coverage was analyzed and used to divide ICSFs into those with a high (≥5%; mean, 10.5%; n=10) versus low (<5%; mean, 1.5%; n=32) amount of plaque coverage per papilla. Demographic and laboratory features were compared between these two groups. Low-plaque stone formers tended to be obese (50% versus 10%; P=0.03) and have a history of urinary tract infection (34% versus 0%; P=0.04). They were less likely to have multiple prior stone events (22% versus 80%; P=0.002) and had a lower mean 24-hour urine calcium excretion (187±86 mg versus 291±99 mg; P<0.01). Morphologically, stones from patients with low amounts of plaque lacked a calcium phosphate core by microcomputed tomography. Papillary biopsies from low plaque stone-formers revealed less interstitial and basement membrane punctate crystallization. These findings suggest that other pathways independent of Randall's plaque may contribute to stone pathogenesis among a subgroup of ICSFs who harbor low amounts of plaque. Copyright © 2014 by the American Society of Nephrology.

Histopathology Predicts the Mechanism of Stone Formation

NASA Astrophysics Data System (ADS)

Evan, Andrew P.

2007-04-01

About 5% of American women and 12% of men will develop a kidney stone at some time in their life and these numbers appear to be on the rise. Despite years of scientific research into the mechanisms of stone formation and growth, limited advances have been made until recently. Randall's original observations and thoughts on the mechanisms for kidney stone formation have been validated for idiopathic calcium oxalate stone formers (ICSF) but not for most other stone forming groups. Our current studies on selected groups of human stone formers using intraoperative papillary biopsies has shown overwhelming evidence for the presence of Randall's plaque in ICSF and that stone formation and growth are exclusively linked to its availability to urinary ions and proteins. Intense investigation of the plaque-stone junction is needed if we are to understand the factors leading to the overgrowth process on exposed regions of plaque. Such information should allow the development of treatment strategies to block stone formation in ICSF patients. Patients who form brushite stones, or who form apatite stones because of distal renal tubular acidosis (dRTA), or patients with calcium oxalate stones due to obesity bypass procedures, or patients with cystinuria, get plugged inner medullary collecting ducts (IMCD) which leads to total destruction of the lining cells and focal sites of interstitial fibrosis. These stone formers have plaque but at levels equal to or below non-stone formers, which would suggest that they form stones by a different mechanism than do ICSF patients.

Inhibition of Tongue Coat and Dental Plaque Formation by Stabilized Chlorine Dioxide Vs Chlorhexidine Mouthrinse: A Randomized, Triple Blinded Study

PubMed Central

Kini, Vineet Vaman; Padhye, Ashvini

2015-01-01

Background Chlorine dioxide (ClO2) is an oxidizing agent with known bactericidal, viricidal and fungicidal properties. Its efficacy in reducing the halitosis has been established by previous literature. However, data evaluating its antiplaque property is scarce. Chlorhexidine (CHX) is considered as the gold standard and an effective adjunctive to mechanical plaque removal. However, it is associated with few reversible side effects. Therefore a study was conducted to assess the antiplaque property of ClO2 containing mouthrinse against CHX mouthrinse. Aims and Objectives To evaluate the efficacy of stabilized chlorine dioxide containing mouthrinse and CHX containing mouthrinse in inhibition of tongue coat accumulation and dental plaque formation using a four day plaque regrowth model clinically and microbiologically in a healthy dental cohort. Materials and Methods A Single Center, Randomized, Triple blinded, Microbiological clinical trial was conducted involving 25 healthy dental students volunteers (11 males, 14 females). Two commercially available mouthrinse: Mouthrinse A – Aqueous based ClO2 mouthrinse Freshchlor® and Mouthrinse B - Aqueous based 0.2% CHX mouthrinse Hexidine® were selected as the test products. Subjects were asked to rinse and gargle for 1 minute with the allocated mouthrinse under supervision after supragingival scaling, polishing and tongue coat removal. After four hours, smears were taken from the buccal mucosa and tooth surface. On the fifth day from baseline of four day non brushing plaque regrowth model the samples were again taken from buccal mucosa and tooth surface followed by recording of plaque scores by Rastogi Modification of Navy Plaque index, extent of tongue coat by Winkel’s tongue coating index and measuring tongue coat wet weight in grams. The samples collected were subjected to microbial analysis and the results were expressed as colony forming units (CFUs) per sample. Statistical Analysis The Data was analysed using SPSS 16.00 and presented using descriptive statistics. Independent t-test was used for the comparison between mouthrinse A groups & mouthrinse B group. Results The plaque scores and Winkels tongue coat scores, wet tongue coat weight recorded on the fifth day after the use of the two mouthrinse didn’t show a statistically significant difference. The CFU per sample from tooth and mucosa after four hours revealed low bacteria count with respect to mouthrinse B however the CFU obtained on the fifth day did not show a statistically significant difference between the two mouthrinse. Conclusion The clinical antiplaque efficacy of CHX and ClO2 mouthwash is comparable and so is the efficacy in reducing the oral bacterial load. PMID:26501017

Short term clinical effect of active and inactive Salvadora persica miswak on dental plaque and gingivitis.

PubMed

Sofrata, Abier; Brito, Fernanda; Al-Otaibi, Meshari; Gustafsson, Anders

2011-10-11

Salvadora persica shrub has been used traditionally in folk medicine for different medical condition treatments. The habitual use of Salvadora persica roots (chewing sticks) for dental hygiene is still wildly spread throughout parts of Asia, Africa, and Middle. It is one of the most important species with its reported strong antibacterial, antifungal, and antiviral effects. Mechanical removal of dental plaque is regarded as an effective mean of controlling progression of periodontal disease. To evaluate the effect of active and inactive miswak on dental plaque, subgingival microbiota and gingival inflammation in patients with gingivitis. In this double blinded randomized controlled trial 68 gingivitis patients were randomly assigned to either active or inactive miswak group, and were instructed to use only issued miswaks for oral hygiene during 3 weeks experimental period. Registration of plaque, gingival inflammation, and plaque samples were taken at baseline and on completion of the study. Plaque samples were analyzed by DNA-DNA hybridization technique. Active miswak significantly reduced dental plaque (p = 0.007). There were no differences between active and inactive miswak in reduction of approximal plaque and composition of subgingival microbiota. Miswak has an overall effect on dental plaque and gingival inflammation scores. Similar results were achieved by active and inactive miswak in difficult to reach areas, indicating miswak has limited chemical effects on this study population. Therefore, miswak can be used as a dental hygiene method in conjunction with interproximal cleaning aides. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Complement factor C5a induces atherosclerotic plaque disruptions

PubMed Central

Wezel, Anouk; de Vries, Margreet R; Lagraauw, H Maxime; Foks, Amanda C; Kuiper, Johan; Quax, Paul HA; Bot, Ilze

2014-01-01

Complement factor C5a and its receptor C5aR are expressed in vulnerable atherosclerotic plaques; however, a causal relation between C5a and plaque rupture has not been established yet. Accelerated atherosclerosis was induced by placing vein grafts in male apoE−/− mice. After 24 days, when advanced plaques had developed, C5a or PBS was applied locally at the lesion site in a pluronic gel. Three days later mice were killed to examine the acute effect of C5a on late stage atherosclerosis. A significant increase in C5aR in the plaque was detectable in mice treated with C5a. Lesion size and plaque morphology did not differ between treatment groups, but interestingly, local treatment with C5a resulted in a striking increase in the amount of plaque disruptions with concomitant intraplaque haemorrhage. To identify the potential underlying mechanisms, smooth muscle cells and endothelial cells were treated in vitro with C5a. Both cell types revealed a marked increase in apoptosis after stimulation with C5a, which may contribute to lesion instability in vivo. Indeed, apoptosis within the plaque was seen to be significantly increased after C5a treatment. We here demonstrate a causal role for C5a in atherosclerotic plaque disruptions, probably by inducing apoptosis. Therefore, intervention in complement factor C5a signalling may be a promising target in the prevention of acute atherosclerotic complications. PMID:25124749

Functional expression of dental plaque microbiota.

PubMed

Peterson, Scott N; Meissner, Tobias; Su, Andrew I; Snesrud, Erik; Ong, Ana C; Schork, Nicholas J; Bretz, Walter A

2014-01-01

Dental caries remains a significant public health problem and is considered pandemic worldwide. The prediction of dental caries based on profiling of microbial species involved in disease and equally important, the identification of species conferring dental health has proven more difficult than anticipated due to high interpersonal and geographical variability of dental plaque microbiota. We have used RNA-Seq to perform global gene expression analysis of dental plaque microbiota derived from 19 twin pairs that were either concordant (caries-active or caries-free) or discordant for dental caries. The transcription profiling allowed us to define a functional core microbiota consisting of nearly 60 species. Similarities in gene expression patterns allowed a preliminary assessment of the relative contribution of human genetics, environmental factors and caries phenotype on the microbiota's transcriptome. Correlation analysis of transcription allowed the identification of numerous functional networks, suggesting that inter-personal environmental variables may co-select for groups of genera and species. Analysis of functional role categories allowed the identification of dominant functions expressed by dental plaque biofilm communities, that highlight the biochemical priorities of dental plaque microbes to metabolize diverse sugars and cope with the acid and oxidative stress resulting from sugar fermentation. The wealth of data generated by deep sequencing of expressed transcripts enables a greatly expanded perspective concerning the functional expression of dental plaque microbiota.

Functional expression of dental plaque microbiota

PubMed Central

Peterson, Scott N.; Meissner, Tobias; Su, Andrew I.; Snesrud, Erik; Ong, Ana C.; Schork, Nicholas J.; Bretz, Walter A.

2014-01-01

Dental caries remains a significant public health problem and is considered pandemic worldwide. The prediction of dental caries based on profiling of microbial species involved in disease and equally important, the identification of species conferring dental health has proven more difficult than anticipated due to high interpersonal and geographical variability of dental plaque microbiota. We have used RNA-Seq to perform global gene expression analysis of dental plaque microbiota derived from 19 twin pairs that were either concordant (caries-active or caries-free) or discordant for dental caries. The transcription profiling allowed us to define a functional core microbiota consisting of nearly 60 species. Similarities in gene expression patterns allowed a preliminary assessment of the relative contribution of human genetics, environmental factors and caries phenotype on the microbiota's transcriptome. Correlation analysis of transcription allowed the identification of numerous functional networks, suggesting that inter-personal environmental variables may co-select for groups of genera and species. Analysis of functional role categories allowed the identification of dominant functions expressed by dental plaque biofilm communities, that highlight the biochemical priorities of dental plaque microbes to metabolize diverse sugars and cope with the acid and oxidative stress resulting from sugar fermentation. The wealth of data generated by deep sequencing of expressed transcripts enables a greatly expanded perspective concerning the functional expression of dental plaque microbiota. PMID:25177549

Calorie restriction attenuates astrogliosis but not amyloid plaque load in aged rhesus macaques: a preliminary quantitative imaging study

PubMed Central

Sridharan, Aadhavi; Pehar, Mariana; Salamat, M Shahriar; Pugh, Thomas D; Bendlin, Barbara B; Willette, Auriel A; Anderson, Rozalyn M; Kemnitz, Joseph W; Colman, Ricki J; Weindruch, Richard H; Puglielli, Luigi; Johnson, Sterling C

2013-01-01

While moderate calorie restriction (CR) in the absence of malnutrition has been consistently shown to have a systemic, beneficial effect against aging in several animals models, its effect on the brain microstructure in a non-human primate model remains to be studied using post-mortem histopathologic techniques. In the present study, we investigated differences in expression levels of glial fibrillary acid protein (GFAP) and β-amyloid plaque load in the hippocampus and the adjacent cortical areas of 7 Control (ad libitum)-fed and 6 CR male rhesus macaques using immunostaining methods. CR monkeys expressed significantly lower levels (∼30% on average) of GFAP than Controls in the CA region of the hippocampus and entorhinal cortex, suggesting a protective effect of CR in limiting astrogliosis. These results recapitulate the neuroprotective effects of CR seen in shorter-lived animal models. There was a significant positive association between age and average amyloid plaque pathology in these animals, but there was no significant difference in amyloid plaque distribution between the two groups. Two of the seven Control animals (28.6%) and one of the six CR animal (16.7%) did not express any amyloid plaques, five of seven Controls (71.4%) and four of six CR animals (66.7%) expressed minimal to moderate amyloid pathology, and one of six CR animals (16.7%) expressed severe amyloid pathology. That CR affects levels of GFAP expression but not amyloid plaque load provides some insight into the means by which CR is beneficial at the microstructural level, potentially by offsetting the increased load of oxidatively damaged proteins, in this non-human primate model of aging. The present study is a preliminary post-mortem histological analysis of the effects of CR on brain health, and further studies using molecular and biochemical techniques are warranted to elucidate underlying mechanisms. PMID:23473840

Impact of Multiple Complex Plaques on Short-and Long-Term Clinical in Patients Presenting with ST-Segment Elevation Myocardial Infarction (From the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction [HORIZONS-AMI] Trial)

PubMed Central

Keeley, Ellen C.; Mehran, Roxana; Brener, Sorin J.; Witzenbichler, Bernhard; Guagliumi, Giulio; Dudek, Dariusz; Kornowski, Ran; Dressler, Ovidiu; Fahy, Martin; Xu, Ke; Grines, Cindy L.; Stone, Gregg W.

2014-01-01

It is not known whether the extent and severity of non-culprit coronary lesions correlate with outcomes in patients with STEMI referred for primary PCI. We sought to quantify complex plaques in ST-segment elevation myocardial infarction (STEMI) patients referred for primary percutaneous coronary intervention (PCI) and to determine their effect on short- and long-term clinical outcomes by examining the core laboratory database for plaque analysis from the HORIZONS-AMI study. Baseline demographic, angiographic, and procedural details were compared between patients with single vs. multiple complex plaques undergoing single vessel PCI. Multivariable analysis was performed for predictors of long-term major adverse cardiac events (MACE), a combined end point of death, reinfarction, ischemic target vessel revascularization, or stroke, and for death alone. Single vessel PCI was performed in 3,137 patients (87%): 2,174 (69%) had multiple complex plaques and 963 (31%) had a single complex plaque. Compared to those with a single complex plaque, patients with multiple complex plaques were older (p<0.0001) and had more comorbidities. The presence of multiple complex plaques was an independent predictor of 3-year MACE (hazard ratio [HR]: 1.58; 95% confidence interval [CI]: 1.26–1.98, p<0.0001), and death alone (HR: 1.68; 95% CI: 1.05–2.70, p=0.03). In conclusion, multiple complex plaques are present in the majority of STEMI patients undergoing primary PCI and their presence is an independent predictor of short- and long-term MACE, including death. (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction [HORIZONS-AMI]; NCT00433966) PMID:24703369

Cluster analysis: a new approach for identification of underlying risk factors for coronary artery disease in essential hypertensive patients.

PubMed

Guo, Qi; Lu, Xiaoni; Gao, Ya; Zhang, Jingjing; Yan, Bin; Su, Dan; Song, Anqi; Zhao, Xi; Wang, Gang

2017-03-07

Grading of essential hypertension according to blood pressure (BP) level may not adequately reflect clinical heterogeneity of hypertensive patients. This study was carried out to explore clinical phenotypes in essential hypertensive patients using cluster analysis. This study recruited 513 hypertensive patients and evaluated BP variations with ambulatory blood pressure monitoring. Four distinct hypertension groups were identified using cluster analysis: (1) younger male smokers with relatively high BP had the most severe carotid plaque thickness but no coronary artery disease (CAD); (2) older women with relatively low diastolic BP had more diabetes; (3) non-smokers with a low systolic BP level had neither diabetes nor CAD; (4) hypertensive patients with BP reverse dipping were most likely to have CAD but had least severe carotid plaque thickness. In binary logistic analysis, reverse dipping was significantly associated with prevalence of CAD. Cluster analysis was shown to be a feasible approach for investigating the heterogeneity of essential hypertension in clinical studies. BP reverse dipping might be valuable for prediction of CAD in hypertensive patients when compared with carotid plaque thickness. However, large-scale prospective trials with more information of plaque morphology are necessary to further compare the predicative power between BP dipping pattern and carotid plaque.

Cluster analysis: a new approach for identification of underlying risk factors for coronary artery disease in essential hypertensive patients

PubMed Central

Guo, Qi; Lu, Xiaoni; Gao, Ya; Zhang, Jingjing; Yan, Bin; Su, Dan; Song, Anqi; Zhao, Xi; Wang, Gang

2017-01-01

Grading of essential hypertension according to blood pressure (BP) level may not adequately reflect clinical heterogeneity of hypertensive patients. This study was carried out to explore clinical phenotypes in essential hypertensive patients using cluster analysis. This study recruited 513 hypertensive patients and evaluated BP variations with ambulatory blood pressure monitoring. Four distinct hypertension groups were identified using cluster analysis: (1) younger male smokers with relatively high BP had the most severe carotid plaque thickness but no coronary artery disease (CAD); (2) older women with relatively low diastolic BP had more diabetes; (3) non-smokers with a low systolic BP level had neither diabetes nor CAD; (4) hypertensive patients with BP reverse dipping were most likely to have CAD but had least severe carotid plaque thickness. In binary logistic analysis, reverse dipping was significantly associated with prevalence of CAD. Cluster analysis was shown to be a feasible approach for investigating the heterogeneity of essential hypertension in clinical studies. BP reverse dipping might be valuable for prediction of CAD in hypertensive patients when compared with carotid plaque thickness. However, large-scale prospective trials with more information of plaque morphology are necessary to further compare the predicative power between BP dipping pattern and carotid plaque. PMID:28266630

Quantitative analysis of the polarization characteristics of atherosclerotic plaques

NASA Astrophysics Data System (ADS)

Gubarkova, Ekaterina V.; Kirillin, Michail Y.; Dudenkova, Varvara V.; Kiseleva, Elena B.; Moiseev, Alexander A.; Gelikonov, Grigory V.; Timofeeva, Lidia B.; Fiks, Ilya I.; Feldchtein, Felix I.; Gladkova, Natalia D.

2016-04-01

In this study we demonstrate the capability of cross-polarization optical coherence tomography (CP OCT) to assess collagen and elastin fibers condition in atherosclerotic plaques basing on ratio of the OCT signal levels in cross- and co- polarizations. We consider the depolarization factor (DF) and the effective birefringence (Δn) as quantitative characteristics of CP OCT images. We revealed that calculation of both DF and Δn in the region of interest (fibrous cap) yields a statistically significant difference between stable and unstable plaques (0.46+/-0.21 vs 0.09+/-0.04 for IDF; (4.7+/-1.0)•10-4 vs (2.5+/-0.7)•10-4 for Δn p<0.05). In parallel with CP OCT we used the nonlinear microscopy for analysis of thin cross-section of atherosclerotic plaque, revealing the different average isotropy index of collagen and elastin fibers for stable and unstable plaques (0.30 +/- 0.10 vs 0.70 +/- 0.08; p<0.001). The proposed approach for quantitative assessment of CP OCT images allows cross-scattering and birefringence characterization of stable and unstable atherosclerotic plaques.

Plaque Echolucency and Stroke Risk in Asymptomatic Carotid Stenosis: A Systematic Review and Meta-Analysis

PubMed Central

Gupta, Ajay; Kesavabhotla, Kartik; Baradaran, Hediyeh; Kamel, Hooman; Pandya, Ankur; Giambrone, Ashley E.; Wright, Drew; Pain, Kevin J.; Mtui, Edward E.; Suri, Jasjit S.; Sanelli, Pina C.; Mushlin, Alvin I.

2014-01-01

Background and Purpose Ultrasonographic plaque echolucency has been studied as a stroke risk marker in carotid atherosclerotic disease. We performed a systematic review and meta-analysis to summarize the association between ultrasound determined carotid plaque echolucency and future ipsilateral stroke risk. Methods We searched the medical literature for studies evaluating the association between carotid plaque echolucency and future stroke in asymptomatic patients. We included prospective observational studies with stroke outcome ascertainment after baseline carotid plaque echolucency assessment. We performed a meta-analysis and assessed study heterogeneity and publication bias. We also performed subgroup analyses limited to patients with stenosis ≥50%, studies in which plaque echolucency was determined via subjective visual interpretation, studies with a relatively lower risk of bias, and studies published after the year 2000. Results We analyzed data from 7 studies on 7557 subjects with a mean follow up of 37.2 months. We found a significant positive relationship between predominantly echolucent (compared to predominantly echogenic) plaques and the risk of future ipsilateral stroke across all stenosis severities (0-99%) (relative risk [RR], 2.31, 95% CI, 1.58-3.39, P<.001) and in subjects with ≥50% stenosis (RR, 2.61 95% CI, 1.47-4.63, P=.001). A statistically significant increased RR for future stroke was preserved in all additional subgroup analyses. No statistically significant heterogeneity or publication bias was present in any of the meta-analyses. Conclusions The presence of ultrasound-determined carotid plaque echolucency provides predictive information in asymptomatic carotid artery stenosis beyond luminal stenosis. However, the magnitude of the increased risk is not sufficient on its own to identify patients likely to benefit from surgical revascularization. PMID:25406150

Chlorhexidine mouthwash reduces plaque and gingivitis.

PubMed

Herrera, David

2013-03-01

Medline, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched along with the reference lists of all selected studies. Only English language studies were included. Randomised controlled clinical trials comparing chlorhexidine (CHX) to placebo/control mouthrinses for oral hygiene in studies of at least four weeks duration were included. Screening, selection and data abstractions were conducted independently by two reviewers. Where possible meta-analysis of weighted mean differences was carried out using fixed or random effects models where appropriate. Thirty studies were included, with 13 studies contributing to the meta-analysis. The meta-analysis found significant differences favouring CHX for a range of indices; the Plaque Index Silness & Löe, Plaque-Index Quigley & Hein (PIQH), the Gingival Index (GI), Papillary BIeeding Index, Bleeding on Marginal Probing and the Lobene Stain Index. Relative to control, the reduction with CHX for plaque was 33% and for gingivitis 26%. CHX rinsing groups demonstrated significantly more staining. In gingivitis patients, CHX mouthrinses together with OH versus placebo, or control mouthrinse provide significant reductions in plaque and gingivitis scores, but a significant increase in staining score.

A multiscale modelling approach to understand atherosclerosis formation: A patient-specific case study in the aortic bifurcation

PubMed Central

Alimohammadi, Mona; Pichardo-Almarza, Cesar; Agu, Obiekezie; Díaz-Zuccarini, Vanessa

2017-01-01

Atherogenesis, the formation of plaques in the wall of blood vessels, starts as a result of lipid accumulation (low-density lipoprotein cholesterol) in the vessel wall. Such accumulation is related to the site of endothelial mechanotransduction, the endothelial response to mechanical stimuli and haemodynamics, which determines biochemical processes regulating the vessel wall permeability. This interaction between biomechanical and biochemical phenomena is complex, spanning different biological scales and is patient-specific, requiring tools able to capture such mathematical and biological complexity in a unified framework. Mathematical models offer an elegant and efficient way of doing this, by taking into account multifactorial and multiscale processes and mechanisms, in order to capture the fundamentals of plaque formation in individual patients. In this study, a mathematical model to understand plaque and calcification locations is presented: this model provides a strong interpretability and physical meaning through a multiscale, complex index or metric (the penetration site of low-density lipoprotein cholesterol, expressed as volumetric flux). Computed tomography scans of the aortic bifurcation and iliac arteries are analysed and compared with the results of the multifactorial model. The results indicate that the model shows potential to predict the majority of the plaque locations, also not predicting regions where plaques are absent. The promising results from this case study provide a proof of concept that can be applied to a larger patient population. PMID:28427316

Endothelial glycocalyx, apoptosis and inflammation in an atherosclerotic mouse model.

PubMed

Cancel, Limary M; Ebong, Eno E; Mensah, Solomon; Hirschberg, Carly; Tarbell, John M

2016-09-01

Previous experiments suggest that both increased endothelial cell apoptosis and endothelial surface glycocalyx shedding could play a role in the endothelial dysfunction and inflammation of athero-prone regions of the vasculature. We sought to elucidate the possibly synergistic mechanisms by which endothelial cell apoptosis and glycocalyx shedding promote atherogenesis. 4- to 6-week old male C57Bl/6 apolipoprotein E knockout (ApoE(-/-)) mice were fed a Western diet for 10 weeks and developed plaques in their brachiocephalic arteries. Glycocalyx coverage and thickness were significantly reduced over the plaque region compared to the non-plaque region (coverage plaque: 71 ± 23%, non-plaque: 97 ± 3%, p = 0.02; thickness plaque: 0.85 ± 0.15 μm, non-plaque: 1.2 ± 0.21 μm, p = 0.006). Values in the non-plaque region were not different from those found in wild type mice fed a normal diet (coverage WT: 92 ± 3%, p = 0.7 vs. non-plaque ApoE(-/-), thickness WT: 1.1 ± 0.06 μm, p = 0.2 vs. non-plaque ApoE(-/-)). Endothelial cell apoptosis was significantly increased in ApoE(-/-) mice compared to wild type mice (ApoE(-/-):64.3 ± 33.0, WT: 1.1 ± 0.5 TUNEL-pos/cm, p = 2 × 10(-7)). The number of apoptotic endothelial cells per unit length was 2 times higher in the plaque region than in the non-plaque region of the same vessel (p = 3 × 10(-5)). Increased expression of matrix metalloproteinase 9 co-localized with glycocalyx shedding and plaque buildup. Our results suggest that, in concert with endothelial apoptosis that increases lipid permeability, glycocalyx shedding initiated by inflammation facilitates monocyte adhesion and macrophage infiltration that promote lipid retention and the development of atherosclerotic plaques. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Quantification of carotid atherosclerotic plaque components using feature space analysis and magnetic resonance imaging.

PubMed

Karmonik, Christof; Basto, Pamela; Morrisett, Joel D

2006-01-01

Atherosclerosis is one of the main causes of cardiovascular disease, accounting for more than one third of all deaths in the United States, there is a growing need to develop non-invasive techniques to assess the severity of atherosclerotic plaque burden. Recent research has suggested that not the size of the atherosclerotic plaque but rather its composition is indicative for plaque rupture as the underlying event of stroke and acute coronary syndrome. With its excellent soft-tissue contrast, magnetic resonance imaging (MRI) is a favored modality for examining plaque composition. In an ex-vivo study, aimed to show the feasibility of quantifying the components of carotid atherosclerotic plaques in-vivo, we acquired multi-contrast MRI images of 13 freshly excised endarterectomy tissues with commercially available MRI sequences and a human surface coil. Feature space analysis (FSA) was utilized in four representative tissues to determine the total relative abundance of calcific, lipidic, fibrotic, thrombotic and normal components as well as in consecutive 2 mm sections across the carotid bifurcation in each tissue. Excellent qualitative agreement between the FSA results and the results obtained from histological methods was observed. This study demonstrates the feasibility of combining MRI with FSA to quantify carotid atherosclerotic plaques in-vivo.

Plaque disruption by coronary computed tomographic angiography in stable patients vs. acute coronary syndrome: a feasibility study.

PubMed

Bilolikar, Abhay N; Goldstein, James A; Madder, Ryan D; Chinnaiyan, Kavitha M

2016-03-01

This study was designed to determine whether coronary CT angiography (CTA) can detect features of plaque disruption in clinically stable patients and to compare lesion prevalence and features between stable patients and those with acute coronary syndrome (ACS). We retrospectively identified patients undergoing CTA, followed by invasive coronary angiography (ICA) within 60 days. Quantitative 3-vessel CTA lesion analysis was performed on all plaques ≥25% stenosis to assess total plaque volume, low attenuation plaque (LAP, <50 HU) volume, and remodelling index. Plaques were qualitatively assessed for CTA features of disruption, including ulceration and intra-plaque dye penetration (IDP). ICA was employed as a reference standard for disruption. A total of 145 (94 ACS and 51 stable) patients were identified. By CTA, plaque disruption was evident in 77.7% of ACS cases. Although more common among those with ACS, CTA also detected plaque disruption in 37.3% of clinically stable patients (P < 0.0001). Clinically stable patients commonly manifest plaques with features of disruption as determined by CTA. Though the prevalence of plaque disruption is less than patients with ACS, these findings support the concept that some clinically stable patients may harbour 'silent' disrupted plaques. These findings may have implications for detection of 'at risk' plaques and patients. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Amyloid-β Plaques in Clinical Alzheimer’s Disease Brain Incorporate Stable Isotope Tracer In Vivo and Exhibit Nanoscale Heterogeneity

PubMed Central

Wildburger, Norelle C.; Gyngard, Frank; Guillermier, Christelle; Patterson, Bruce W.; Elbert, Donald; Mawuenyega, Kwasi G.; Schneider, Theresa; Green, Karen; Roth, Robyn; Schmidt, Robert E.; Cairns, Nigel J.; Benzinger, Tammie L. S.; Steinhauser, Matthew L.; Bateman, Randall J.

2018-01-01

Alzheimer’s disease (AD) is a neurodegenerative disorder with clinical manifestations of progressive memory decline and loss of executive function and language. AD affects an estimated 5.3 million Americans alone and is the most common form of age-related dementia with a rapidly growing prevalence among the aging population—those 65 years of age or older. AD is characterized by accumulation of aggregated amyloid-beta (Aβ) in the brain, which leads to one of the pathological hallmarks of AD—Aβ plaques. As a result, Aβ plaques have been extensively studied after being first described over a century ago. Advances in brain imaging and quantitative measures of Aβ in biological fluids have yielded insight into the time course of plaque development decades before and after AD symptom onset. However, despite the fundamental role of Aβ plaques in AD, in vivo measures of individual plaque growth, growth distribution, and dynamics are still lacking. To address this question, we combined stable isotope labeling kinetics (SILK) and nanoscale secondary ion mass spectrometry (NanoSIMS) imaging in an approach termed SILK–SIMS to resolve plaque dynamics in three human AD brains. In human AD brain, plaques exhibit incorporation of a stable isotope tracer. Tracer enrichment was highly variable between plaques and the spatial distribution asymmetric with both quiescent and active nanometer sub-regions of tracer incorporation. These data reveal that Aβ plaques are dynamic structures with deposition rates over days indicating a highly active process. Here, we report the first, direct quantitative measures of in vivo deposition into plaques in human AD brain. Our SILK–SIMS studies will provide invaluable information on plaque dynamics in the normal and diseased brain and offer many new avenues for investigation into pathological mechanisms of the disease, with implications for therapeutic development. PMID:29623063

Amyloid-β Plaques in Clinical Alzheimer's Disease Brain Incorporate Stable Isotope Tracer In Vivo and Exhibit Nanoscale Heterogeneity.

PubMed

Wildburger, Norelle C; Gyngard, Frank; Guillermier, Christelle; Patterson, Bruce W; Elbert, Donald; Mawuenyega, Kwasi G; Schneider, Theresa; Green, Karen; Roth, Robyn; Schmidt, Robert E; Cairns, Nigel J; Benzinger, Tammie L S; Steinhauser, Matthew L; Bateman, Randall J

2018-01-01

Alzheimer's disease (AD) is a neurodegenerative disorder with clinical manifestations of progressive memory decline and loss of executive function and language. AD affects an estimated 5.3 million Americans alone and is the most common form of age-related dementia with a rapidly growing prevalence among the aging population-those 65 years of age or older. AD is characterized by accumulation of aggregated amyloid-beta (Aβ) in the brain, which leads to one of the pathological hallmarks of AD-Aβ plaques. As a result, Aβ plaques have been extensively studied after being first described over a century ago. Advances in brain imaging and quantitative measures of Aβ in biological fluids have yielded insight into the time course of plaque development decades before and after AD symptom onset. However, despite the fundamental role of Aβ plaques in AD, in vivo measures of individual plaque growth, growth distribution, and dynamics are still lacking. To address this question, we combined stable isotope labeling kinetics (SILK) and nanoscale secondary ion mass spectrometry (NanoSIMS) imaging in an approach termed SILK-SIMS to resolve plaque dynamics in three human AD brains. In human AD brain, plaques exhibit incorporation of a stable isotope tracer. Tracer enrichment was highly variable between plaques and the spatial distribution asymmetric with both quiescent and active nanometer sub-regions of tracer incorporation. These data reveal that Aβ plaques are dynamic structures with deposition rates over days indicating a highly active process. Here, we report the first, direct quantitative measures of in vivo deposition into plaques in human AD brain. Our SILK-SIMS studies will provide invaluable information on plaque dynamics in the normal and diseased brain and offer many new avenues for investigation into pathological mechanisms of the disease, with implications for therapeutic development.

Label-free imaging of atherosclerotic plaques using third-harmonic generation microscopy

PubMed Central

Small, David M.; Jones, Jason S.; Tendler, Irwin I.; Miller, Paul E.; Ghetti, Andre; Nishimura, Nozomi

2017-01-01

Multiphoton microscopy using laser sources in the mid-infrared range (MIR, 1,300 nm and 1,700 nm) was used to image atherosclerotic plaques from murine and human samples. Third harmonic generation (THG) from atherosclerotic plaques revealed morphological details of cellular and extracellular lipid deposits. Simultaneous nonlinear optical signals from the same laser source, including second harmonic generation and endogenous fluorescence, resulted in label-free images of various layers within the diseased vessel wall. The THG signal adds an endogenous contrast mechanism with a practical degree of specificity for atherosclerotic plaques that complements current nonlinear optical methods for the investigation of cardiovascular disease. Our use of whole-mount tissue and backward scattered epi-detection suggests THG could potentially be used in the future as a clinical tool. PMID:29359098

The walking dead: macrophage inflammation and death in atherosclerosis.

PubMed

Kavurma, Mary M; Rayner, Katey J; Karunakaran, Denuja

2017-04-01

To highlight recent studies that describe novel inflammatory and signaling mechanisms that regulate macrophage death in atherosclerosis. Macrophages contribute to all stages of atherosclerosis. The traditional dogma states that in homeostatic conditions, macrophages undergo apoptosis and are efficiently phagocytosed to be cleared by a process called efferocytosis. In advanced atherosclerosis, however, defective efferocytosis results in secondary necrosis of these uncleared apoptotic cells, which ultimately contributes to the formation of the characteristic necrotic core and the vulnerable plaque. Here, we outline the different types of lesional macrophage death: apoptosis, autophagic and the newly defined necroptosis (i.e. a type of programmed necrosis). Recent discoveries demonstrate that macrophage necroptosis directly contributes to necrotic core formation and plaque instability. Further, promoting the resolution of inflammation using preresolving mediators has been shown to enhance efferocytosis and decrease plaque vulnerability. Finally, the canonical 'don't eat me' signal CD47 has recently been described as playing an important role in atherosclerotic lesion progression by impairing efficient efferocytosis. Although we have made significant strides in improving our understanding of cell death and clearance mechanisms in atherosclerosis, there still remains unanswered questions as to how these pathways can be harnessed using therapeutics to promote lesion regression and disease stability. Improving our understanding of the mechanisms that regulate macrophage death in atherosclerosis, in particular apoptosis, necroptosis and efferocytosis, will provide novel therapeutic opportunities to resolve atherosclerosis and promote plaque stability.

Numerical simulation of haemodynamics and low-density lipoprotein transport in the rabbit aorta and their correlation with atherosclerotic plaque thickness

PubMed Central

Liu, Xiao; Zhang, Peng; Feng, Chenglong; Sun, Anqiang; Kang, Hongyan; Deng, Xiaoyan; Fan, Yubo

2017-01-01

Two mechanisms of shear stress and mass transport have been recognized to play an important role in the development of localized atherosclerosis. However, their relationship and roles in atherogenesis are still obscure. It is necessary to investigate quantitatively the correlation among low-density lipoproteins (LDL) transport, haemodynamic parameters and plaque thickness. We simulated blood flow and LDL transport in rabbit aorta using computational fluid dynamics and evaluated plaque thickness in the aorta of a high-fat-diet rabbit. The numerical results show that regions with high luminal LDL concentration tend to have severely negative haemodynamic environments (HEs). However, for regions with moderately and slightly high luminal LDL concentration, the relationship between LDL concentration and the above haemodynamic indicators is not clear cut. Point-by-point correlation with experimental results indicates that severe atherosclerotic plaque corresponds to high LDL concentration and seriously negative HEs, less severe atherosclerotic plaque is related to either moderately high LDL concentration or moderately negative HEs, and there is almost no atherosclerotic plaque in regions with both low LDL concentration and positive HEs. In conclusion, LDL distribution is closely linked to blood flow transport, and the synergetic effects of luminal surface LDL concentration and wall shear stress-based haemodynamic indicators may determine plaque thickness. PMID:28424305

Relationship between Plaque Echo, Thickness and Neovascularization Assessed by Quantitative and Semi-quantitative Contrast-Enhanced Ultrasonography in Different Stenosis Groups.

PubMed

Song, Yan; Feng, Jun; Dang, Ying; Zhao, Chao; Zheng, Jie; Ruan, Litao

2017-12-01

The aim of this study was to determine the relationship between plaque echo, thickness and neovascularization in different stenosis groups using quantitative and semi-quantitative contrast-enhanced ultrasound (CEUS) in patients with carotid atherosclerosis plaque. A total of 224 plaques were divided into mild stenosis (<50%; 135 plaques, 60.27%), moderate stenosis (50%-69%; 39 plaques, 17.41%) and severe stenosis (70%-99%; 50 plaques, 22.32%) groups. Quantitative and semi-quantitative methods were used to assess plaque neovascularization and determine the relationship between plaque echo, thickness and neovascularization. Correlation analysis revealed no relationship of neovascularization with plaque echo in the groups using either quantitative or semi-quantitative methods. Furthermore, there was no correlation of neovascularization with plaque thickness using the semi-quantitative method. The ratio of areas under the curve (RAUC) was negatively correlated with plaque thickness (r = -0.317, p = 0.001) in the mild stenosis group. With the quartile method, plaque thickness of the mild stenosis group was divided into four groups, with significant differences between the 1.5-2.2 mm and ≥3.5 mm groups (p = 0.002), 2.3-2.8 mm and ≥3.5 mm groups (p <0.001) and 2.9-3.4 mm and ≥3.5 mm groups (p <0.001). Both semi-quantitative and quantitative CEUS methods characterizing neovascularization of plaque are equivalent with respect to assessing relationships between neovascularization, echogenicity and thickness. However, the quantitative method could fail for plaque <3.5 mm because of motion artifacts. Copyright © 2017 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.

Association of CD147 genetic polymorphisms with carotid atherosclerotic plaques in a Han Chinese population with cerebral infarction.

PubMed

Ni, Tongtian; Chen, Min; Yang, Kang; Shao, Jianwei; Fu, Yi; Zhou, Weijun

2017-08-01

Given the important role of CD147 in the development of atherosclerosis, we speculated that CD147 genetic polymorphisms might influence the formation of carotid atherosclerotic plaques. The study was to investigate the association between CD147 gene polymorphisms and susceptibility to carotid atherosclerotic plaques in individuals with cerebral infarction (CI). Eight SNPs in the regulatory and coding regions of the CD147 gene were examined using polymerase chain reaction-ligase detection reaction (PCR-LDR) in DNA samples from 732 Chinese patients with CI, divided into a carotid plaque group (n=475) and a non-carotid plaque group (n=257). Significant differences were found in the genotypes and allele frequencies of the rs4919862 SNP between the carotid plaque and non-carotid plaque groups of CI patients (P<0.05), while the frequencies of the C allele and the CC genotype in the non-carotid plaque group were significantly lower than those in the carotid plaque group, and the frequencies of the T allele in the non-carotid plaque group were significantly higher than those in the carotid plaque group (P<0.05). In addition, there was strong linkage disequilibrium among the rs4919862, rs8637 and rs8259 sites. In a haplotype analysis, the occurrence rate of the haplotype GATGCAGC was 2.095 times higher in the carotid plaque group than in the non-carotid plaque group (P<0.05). These results showed that the rs4919862 SNP of CD147 was closely associated with carotid atherosclerotic plaques formation. Thus, polymorphisms of the CD147 gene may be related to the tendency for carotid atherosclerotic plaques. Copyright © 2017 Elsevier Ltd. All rights reserved.

Chair-side detection of Prevotella Intermedia in mature dental plaque by its fluorescence.

PubMed

Nomura, Yoshiaki; Takeuchi, Hiroaki; Okamoto, Masaaki; Sogabe, Kaoru; Okada, Ayako; Hanada, Nobuhiro

2017-06-01

Prevotella intermedia/nigrescens is one of the well-known pathogens causing periodontal diseases, and the red florescence excited by the visible blue light caused by the protoporphyrin IX in the bacterial cells could be useful for the chair-side detection. The aim of this study was to evaluated levels of periodontal pathogen, especially P. intermedia in clinical samples of red fluorescent dental plaque. Thirty two supra gingival plaque samples from six individuals were measured its fluorescence at 640nm wavelength excited by 409nm. Periodontopathic bacteria were counted by the Invader PLUS PCR assay. Co-relations the fluorescence intensity and bacterial counts were analyzed by Person's correlation coefficient and simple and multiple regression analysis. Positive and negative predictive values of the fluorescence intensities for with or without P. intermedia in supragingival plaque was calculated. When relative fluorescence unit (RFU) were logarithmic transformed, statistically significant linear relations between RFU and bacterial counts were obtained for P. intermedia, Porphyromonas gingivalis and Tannerella forsythia. By the multiple regression analysis, only P. intermedia had statistically significant co-relation with fluorescence intensities. All of the fluorescent dental plaque contained P. intermedia m. In contrast, 28% of non-fluorescent plaques contained P. intermedia. To check the fluorescence dental plaque in the oral cavity could be the simple chair-side screening of the mature dental plaque before examining the periodontal pathogens especially P. intermedia by the PCR method. Copyright © 2017 Elsevier B.V. All rights reserved.

Matrix vesicles in the fibrous cap of atherosclerotic plaque: possible contribution to plaque rupture.

PubMed

Bobryshev, Y V; Killingsworth, M C; Lord, R S A; Grabs, A J

2008-10-01

Plaque rupture is the most common type of plaque complication and leads to acute ischaemic events such as myocardial infarction and stroke. Calcification has been suggested as a possible indicator of plaque instability. Although the role of matrix vesicles in the initial stages of arterial calcification has been recognized, no studies have yet been carried out to examine a possible role of matrix vesicles in plaque destabilization. Tissue specimens selected for the present study represented carotid specimens obtained from patients undergoing carotid endarterectomy. Serial frozen cross-sections of the tissue specimens were cut and mounted on glass slides. The thickness of the fibrous cap (FCT) in each advanced atherosclerotic lesion, containing a well developed lipid/necrotic core, was measured at its narrowest sites in sets of serial sections. According to established criteria, atherosclerotic plaque specimens were histologically subdivided into two groups: vulnerable plaques with thin fibrous caps (FCT <100 microm) and presumably stable plaques, in which fibrous caps were thicker than 100 microm. Twenty-four carotid plaques (12 vulnerable and 12 presumably stable plaques) were collected for the present analysis of matrix vesicles in fibrous caps. In order to provide a sufficient number of representative areas from each plaque, laser capture microdissection (LCM) was carried out. The quantification of matrix vesicles in ultrathin sections of vulnerable and stable plaques revealed that the numbers of matrix vesicles were significantly higher in fibrous caps of vulnerable plaques than those in stable plaques (8.908+0.544 versus 6.208+0.467 matrix vesicles per 1.92 microm2 standard area; P= 0.0002). Electron microscopy combined with X-ray elemental microanalysis showed that some matrix vesicles in atherosclerotic plaques were undergoing calcification and were characterized by a high content of calcium and phosphorus. The percentage of calcified matrix vesicles/microcalcifications was significantly higher in fibrous caps in vulnerable plaques compared with that in stable plaques (6.705+/-0.436 versus 5.322+/-0494; P= 0.0474). The findings reinforce a view that the texture of the extracellular matrix in the thinning fibrous cap of atherosclerotic plaque is altered and this might contribute to plaque destabilization.

Impaired JIP3-dependent axonal lysosome transport promotes amyloid plaque pathology

PubMed Central

Gowrishankar, Swetha; Wu, Yumei

2017-01-01

Lysosomes robustly accumulate within axonal swellings at Alzheimer’s disease (AD) amyloid plaques. However, the underlying mechanisms and disease relevance of such lysosome accumulations are not well understood. Motivated by these problems, we identified JNK-interacting protein 3 (JIP3) as an important regulator of axonal lysosome transport and maturation. JIP3 knockout mouse neuron primary cultures accumulate lysosomes within focal axonal swellings that resemble the dystrophic axons at amyloid plaques. These swellings contain high levels of amyloid precursor protein processing enzymes (BACE1 and presenilin 2) and are accompanied by elevated Aβ peptide levels. The in vivo importance of the JIP3-dependent regulation of axonal lysosomes was revealed by the worsening of the amyloid plaque pathology arising from JIP3 haploinsufficiency in a mouse model of AD. These results establish the critical role of JIP3-dependent axonal lysosome transport in regulating amyloidogenic amyloid precursor protein processing and support a model wherein Aβ production is amplified by plaque-induced axonal lysosome transport defects. PMID:28784610

Long life nickel electrodes for a nickel-hydrogen cell: Cycle life tests

NASA Technical Reports Server (NTRS)

Lim, H. S.; Verzwyvelt, S. A.

1985-01-01

In order to develop a long life nickel electrode for a Ni/H2 cell, the cycle life of nickel electrodes was tested in Ni/H2 boiler plate cells. A 19 test cell matrix was made of various nickel electrode designs including three levels each of plaque mechanical strength, median pore size of the plaque, and active material loading. Test cells were cycled to the end of their life (0.5v) in a 45 minute low Earth orbit cycle regime at 80% depth-of-discharge. It is shown that the active material loading level affects the cycle life the most with the optimum loading at 1.6 g/cc void. Mechanical strength does not affect the cycle life noticeably in the bend strength range of 400 to 700 psi. It is found that the best plaque is made of INCO nickel powder type 287 and has median pore size of 13 micron.

Xanthine Oxidase Inhibition by Febuxostat Attenuates Experimental Atherosclerosis in Mice

PubMed Central

Nomura, Johji; Busso, Nathalie; Ives, Annette; Matsui, Chieko; Tsujimoto, Syunsuke; Shirakura, Takashi; Tamura, Mizuho; Kobayashi, Tsunefumi; So, Alexander; Yamanaka, Yoshihiro

2014-01-01

Atherosclerosis is a chronic inflammatory disease due to lipid deposition in the arterial wall. Multiple mechanisms participate in the inflammatory process, including oxidative stress. Xanthine oxidase (XO) is a major source of reactive oxygen species (ROS) and has been linked to the pathogenesis of atherosclerosis, but the underlying mechanisms remain unclear. Here, we show enhanced XO expression in macrophages in the atherosclerotic plaque and in aortic endothelial cells in ApoE−/− mice, and that febuxostat, a highly potent XO inhibitor, suppressed plaque formation, reduced arterial ROS levels and improved endothelial dysfunction in ApoE−/− mice without affecting plasma cholesterol levels. In vitro, febuxostat inhibited cholesterol crystal-induced ROS formation and inflammatory cytokine release in murine macrophages. These results demonstrate that in the atherosclerotic plaque, XO-mediated ROS formation is pro-inflammatory and XO-inhibition by febuxostat is a potential therapy for atherosclerosis. PMID:24686534

Detection of High-Risk Atherosclerotic Plaque

PubMed Central

Fleg, Jerome L.; Stone, Gregg W.; Fayad, Zahi A.; Granada, Juan F.; Hatsukami, Thomas S.; Kolodgie, Frank D.; Ohayon, Jacques; Pettigrew, Roderic; Sabatine, Marc S.; Tearney, Guillermo; Waxman, Sergio; Domanski, Michael J.; Srinivas, Pothur R.; Narula, Jagat

2013-01-01

The leading cause of major morbidity and mortality in most countries around the world is atherosclerotic cardiovascular disease, most commonly caused by thrombotic occlusion of a high-risk coronary plaque resulting in myocardial infarction or cardiac death, or embolization from a high-risk carotid plaque resulting in stroke. The lesions prone to result in such clinical events are termed vulnerable or high-risk plaques, and their identification may lead to the development of pharmacological and mechanical intervention strategies to prevent such events. Autopsy studies from patients dying of acute myocardial infarction or sudden death have shown that such events typically arise from specific types of atherosclerotic plaques, most commonly the thin-cap fibroatheroma. However, the search in human beings for vulnerable plaques before their becoming symptomatic has been elusive. Recently, the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study demonstrated that coronary plaques that are likely to cause future cardiac events, regardless of angiographic severity, are characterized by large plaque burden and small lumen area and/or are thin-cap fibroatheromas verified by radiofrequency intravascular ultrasound imaging. This study opened the door to identifying additional invasive and noninvasive imaging modalities that may improve detection of high-risk atherosclerotic lesions and patients. Beyond classic risk factors, novel biomarkers and genetic profiling may identify those patients in whom noninvasive imaging for vulnerable plaque screening, followed by invasive imaging for risk confirmation is warranted, and in whom future pharmacological and/or device-based focal or regional therapies may be applied to improve long-term prognosis. PMID:22974808

Spectrometric analysis and scanning electronic microscopy of two pleural plaques from mediaeval Portuguese period.

PubMed

Fernandes, T; Granja, R; Thillaud, P L

2014-01-01

During an archaeological excavation at a mediaeval monastery (Flor da Rosa, Crato, Portugal), a skeleton of a adult woman was found with two calcifications in the thoracic cage. The location and the macroscopic analysis of the calcifications allowed them to be assigned as pleural plaques. Spectrometric analysis and scanning electronic microscopy enabled to establish that it originated with an infectious process. These results associated with the lesions found in the ribs and vertebrae strongly suggest tuberculosis as the cause of these pleural plaques. Copyright © 2013 Sociedade Portuguesa de Pneumologia. Published by Elsevier España. All rights reserved.

Predict value of adiponectin for coronary atherosclerosis plaques according to computed tomography angiography in an asymptomatic population.

PubMed

Gan, Lu; Yang, Li; Yan, Guangtao

2018-05-25

The association between serum adiponectin levels and coronary atherosclerosis plaque characteristics in asymptomatic populations is unclear. To examine the predictive value of serum adiponectin levels for coronary high risk plaques as detected by computed tomography angiography (CTA). This was a cross-sectional study. All patients were divided into high risk plaque group and non high risk plaque group. The FRS was calculated for each patient. CTA was performed for each patient. Adiponectin levels were measured by flow fluorescence immunmicrobead assay (FFIA). Receiver-operating characteristic (ROC) curves and multivariate analysis was used to determine the predictive value of adiponectin for high risk plaques. The high risk plaque group showed lower adiponectin levels than non high risk plaque group (median, 7.27 vs. 8.51 μg/ml, P = 0.003). The multivariate analysis showed that age (OR = 2.62, 95%CI: 1.51-4.56, P = 0.001), hyperlipidemia (OR = 1.89, 95%CI: 1.07-3.36, P = 0.029), high-density lipoprotein cholesterol (HDL-C) (OR = 0.46, 95%CI: 0.24-0.87, P = 0.02), the ratio of total cholesterol to high-density lipoproteincholesterol (TC/HDL-C) (OR = 0.69, 95%CI: 0.50-0.94, P = 0.02), apolipoprotein B (apoB) (OR = 3.08, 95%CI: 1.50-6.32, P = 0.002), and adiponectin (OR = 0.37, 95%CI: 0.19-0.74, P = 0.005) were independently associated with the presence of high risk plaques. AUC of the multivariate model for high-risk plaques was 0.728 (95%CI: 0.627-0.783). Sensitivity was 74.9%, specificity was 60.2%, the positive predictive value was 65.3%, and the negative predictive value was 70.6%. Decreased adiponectin levels were associated with the presence of high-risk plaques in asymptomatic populations at low to intermediate FRS. Adiponectin can play an important role in plaque screening before coronary CTA. Copyright © 2018 Elsevier Inc. All rights reserved.

The influence of constitutive law choice used to characterise atherosclerotic tissue material properties on computing stress values in human carotid plaques.

PubMed

Teng, Zhongzhao; Yuan, Jianmin; Feng, Jiaxuan; Zhang, Yongxue; Brown, Adam J; Wang, Shuo; Lu, Qingsheng; Gillard, Jonathan H

2015-11-05

Calculating high stress concentration within carotid atherosclerotic plaques has been shown to be complementary to anatomical features in assessing vulnerability. Reliability of stress calculation may depend on the constitutive laws/strain energy density functions (SEDFs) used to characterize tissue material properties. Different SEDFs, including neo-Hookean, one-/two-term Ogden, Yeoh, 5-parameter Mooney-Rivlin, Demiray and modified Mooney-Rivlin, have been used to describe atherosclerotic tissue behavior. However, the capacity of SEDFs to fit experimental data and the difference in the stress calculation remains unexplored. In this study, seven SEDFs were used to fit the stress-stretch data points of media, fibrous cap, lipid and intraplaque hemorrhage/thrombus obtained from 21 human carotid plaques. Semi-analytic solution, 2D structure-only and 3D fully coupled fluid-structure interaction (FSI) analyses were used to quantify stress using different SEDFs and the related material stability examined. Results show that, except for neo-Hookean, all other six SEDFs fitted the experimental points well, with vessel stress distribution in the circumferential and radial directions being similar. 2D structural-only analysis was successful for all seven SEDFs, but 3D FSI were only possible with neo-Hookean, Demiray and modified Mooney-Rivlin models. Stresses calculated using Demiray and modified Mooney-Rivlin models were nearly identical. Further analyses indicated that the energy contours of one-/two-term Ogden and 5-parameter Mooney-Rivlin models were not strictly convex and the material stability indictors under homogeneous deformations were not always positive. In conclusion, considering the capacity in characterizing material properties and stabilities, Demiray and modified Mooney-Rivlin SEDF appear practical choices for mechanical analyses to predict the critical mechanical conditions within carotid atherosclerotic plaques. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Clinical validation of robot simulation of toothbrushing - comparative plaque removal efficacy

PubMed Central

2014-01-01

Background Clinical validation of laboratory toothbrushing tests has important advantages. It was, therefore, the aim to demonstrate correlation of tooth cleaning efficiency of a new robot brushing simulation technique with clinical plaque removal. Methods Clinical programme: 27 subjects received dental cleaning prior to 3-day-plaque-regrowth-interval. Plaque was stained, photographically documented and scored using planimetrical index. Subjects brushed teeth 33–47 with three techniques (horizontal, rotating, vertical), each for 20s buccally and for 20s orally in 3 consecutive intervals. The force was calibrated, the brushing technique was video supported. Two different brushes were randomly assigned to the subject. Robot programme: Clinical brushing programmes were transfered to a 6-axis-robot. Artificial teeth 33–47 were covered with plaque-simulating substrate. All brushing techniques were repeated 7 times, results were scored according to clinical planimetry. All data underwent statistical analysis by t-test, U-test and multivariate analysis. Results The individual clinical cleaning patterns are well reproduced by the robot programmes. Differences in plaque removal are statistically significant for the two brushes, reproduced in clinical and robot data. Multivariate analysis confirms the higher cleaning efficiency for anterior teeth and for the buccal sites. Conclusions The robot tooth brushing simulation programme showed good correlation with clinically standardized tooth brushing. This new robot brushing simulation programme can be used for rapid, reproducible laboratory testing of tooth cleaning. PMID:24996973

Clinical validation of robot simulation of toothbrushing--comparative plaque removal efficacy.

PubMed

Lang, Tomas; Staufer, Sebastian; Jennes, Barbara; Gaengler, Peter

2014-07-04

Clinical validation of laboratory toothbrushing tests has important advantages. It was, therefore, the aim to demonstrate correlation of tooth cleaning efficiency of a new robot brushing simulation technique with clinical plaque removal. Clinical programme: 27 subjects received dental cleaning prior to 3-day-plaque-regrowth-interval. Plaque was stained, photographically documented and scored using planimetrical index. Subjects brushed teeth 33-47 with three techniques (horizontal, rotating, vertical), each for 20s buccally and for 20s orally in 3 consecutive intervals. The force was calibrated, the brushing technique was video supported. Two different brushes were randomly assigned to the subject. Robot programme: Clinical brushing programmes were transfered to a 6-axis-robot. Artificial teeth 33-47 were covered with plaque-simulating substrate. All brushing techniques were repeated 7 times, results were scored according to clinical planimetry. All data underwent statistical analysis by t-test, U-test and multivariate analysis. The individual clinical cleaning patterns are well reproduced by the robot programmes. Differences in plaque removal are statistically significant for the two brushes, reproduced in clinical and robot data. Multivariate analysis confirms the higher cleaning efficiency for anterior teeth and for the buccal sites. The robot tooth brushing simulation programme showed good correlation with clinically standardized tooth brushing.This new robot brushing simulation programme can be used for rapid, reproducible laboratory testing of tooth cleaning.

Evaluation of carotid plaque echogenicity based on the integral of the cumulative probability distribution using gray-scale ultrasound images.

PubMed

Huang, Xiaowei; Zhang, Yanling; Meng, Long; Abbott, Derek; Qian, Ming; Wong, Kelvin K L; Zheng, Rongqing; Zheng, Hairong; Niu, Lili

2017-01-01

Carotid plaque echogenicity is associated with the risk of cardiovascular events. Gray-scale median (GSM) of the ultrasound image of carotid plaques has been widely used as an objective method for evaluation of plaque echogenicity in patients with atherosclerosis. We proposed a computer-aided method to evaluate plaque echogenicity and compared its efficiency with GSM. One hundred and twenty-five carotid plaques (43 echo-rich, 35 intermediate, 47 echolucent) were collected from 72 patients in this study. The cumulative probability distribution curves were obtained based on statistics of the pixels in the gray-level images of plaques. The area under the cumulative probability distribution curve (AUCPDC) was calculated as its integral value to evaluate plaque echogenicity. The classification accuracy for three types of plaques is 78.4% (kappa value, κ = 0.673), when the AUCPDC is used for classifier training, whereas GSM is 64.8% (κ = 0.460). The receiver operating characteristic curves were produced to test the effectiveness of AUCPDC and GSM for the identification of echolucent plaques. The area under the curve (AUC) was 0.817 when AUCPDC was used for training the classifier, which is higher than that achieved using GSM (AUC = 0.746). Compared with GSM, the AUCPDC showed a borderline association with coronary heart disease (Spearman r = 0.234, p = 0.050). Our experimental results suggest that AUCPDC analysis is a promising method for evaluation of plaque echogenicity and predicting cardiovascular events in patients with plaques.

Mathematical modeling of coupled drug and drug-encapsulated nanoparticle transport in patient-specific coronary artery walls

NASA Astrophysics Data System (ADS)

Hossain, Shaolie S.; Hossainy, Syed F. A.; Bazilevs, Yuri; Calo, Victor M.; Hughes, Thomas J. R.

2012-02-01

The majority of heart attacks occur when there is a sudden rupture of atherosclerotic plaque, exposing prothrombotic emboli to coronary blood flow, forming clots that can cause blockages of the arterial lumen. Diseased arteries can be treated with drugs delivered locally to vulnerable plaques. The objective of this work was to develop a computational tool-set to support the design and analysis of a catheter-based nanoparticulate drug delivery system to treat vulnerable plaques and diffuse atherosclerosis. A three-dimensional mathematical model of coupled mass transport of drug and drug-encapsulated nanoparticles was developed and solved numerically utilizing isogeometric finite element analysis. Simulations were run on a patient-specific multilayered coronary artery wall segment with a vulnerable plaque and the effect of artery and plaque inhomogeneity was analyzed. The method captured trends observed in local drug delivery and demonstrated potential for optimizing drug design parameters, including delivery location, nanoparticle surface properties, and drug release rate.

[Imprints of coronary plaque particles in the PTCA balloon surface during the dilatation processing].

PubMed

Werner, D; Behrend, D; Schmitz, K P; Urbaszek, W

1995-05-01

Seventy-six PTCA-balloons after coronary angioplasty were studied for superficial changes using scanning electron microscopy (SEM) after fixing in glutardialdehyde. Coronary plaque particles were identified on the balloon surface in 52 cases (68%). Twelve new and unused balloons were subjected to the same chemical treatment and SEM showed no imprints. The average length of the longest imprinted plaques was 128 +/- 201 microns and the average number of plaque particles per balloon was 4.9 +/- 2.7. The maximal dilatation pressure and the number of dilatations showed no influence on the impregnation of plaque particles. However, longer plaque imprints tended to occur under low dilatation pressure. Imprints of plaque particles were significantly higher in patients with low cholesterol (p = 0.0001) and low triglycerides (p = 0.0016). No correlation was seen between imprint length and lipid levels. Similarly, the different balloon materials (polyethylene, polyolefincopolymer) showed no significant differences with regard to plaque occurrence. The PTCA-balloons, plaque particles and six coronary plaques obtained after endatherectomy were subjected to energy dispersive x-ray analysis (EDX) under SEM as EDX reveals qualitative and quantitative information about the structural elements. Highly significant differences in calcium, sodium, phosphorus and silicon contents (p = 0.0000) between plaque particles and balloon surface were observed, owing to the absence of these in balloon material. Thus EDX offers additional advantages over SEM in that it clearly differentiates deformed balloon surface, plaque particle, and retained contrast medium. Plaque particles can be recovered from balloon surfaces after PTCA. Depending upon their size, they could lead to coronary spasm or microembolic phenomenon.

Aspartame Intake Relates to Coronary Plaque Burden and Inflammatory Indices in Human Immunodeficiency Virus

PubMed Central

Hall, Leangelo N.; Sanchez, Laura R.; Hubbard, Jane; Lee, Hang; Looby, Sara E.; Srinivasa, Suman; Zanni, Markella V.; Stanley, Takara L.; Lo, Janet; Grinspoon, Steven K.

2017-01-01

Abstract Background. Dietary sweeteners may contribute to metabolic dysregulation and cardiovascular disease (CVD), but this has not been assessed in human immunodeficiency virus (HIV). Methods. One hundred twenty-four HIV-infected and 56 non-HIV-infected participants, without history of known coronary artery disease were included. Dietary intake was assessed using a 4-day food record. Coronary plaque was determined using cardiac computed tomography angiography. Results. Human immunodeficiency virus-infected participants had significantly greater intake of dietary sweeteners, including total sugar (P = .03) and added sugar (P = .009); intake of aspartame (artificial sweetener) was greater among aspartame consumers with HIV versus non-HIV consumers (P = .03). Among HIV-infected participants, aspartame intake was significantly associated with coronary plaque (P = .002) and noncalcified plaque (P = .007) segments, as well as markers of inflammation/immune activation (monocyte chemoattractant protein 1 and lipoprotein-associated phospholipase A2), which may contribute to increased atherogenesis. In multivariable regression modeling, aspartame remained an independent predictor of plaque in HIV. In contrast, among non-HIV-infected participants, no sweetener type was shown to relate to plaque characteristics. Conclusions. We demonstrate increased intake of dietary sweeteners and a potential novel association between aspartame intake, plaque burden, and inflammation in HIV. Our data suggest that aspartame may contribute to CVD risk in HIV. Further studies should address potential mechanisms by which aspartame may contribute to increased plaque burden and cardiovascular benefits of dietary strategies targeting aspartame intake in HIV. PMID:28695142

Recent Advances in Fluorescent Angioscopy for Molecular Imaging of Human Atherosclerotic Coronary Plaque

PubMed Central

2017-01-01

Purpose of Review: In vivo imaging of the native substances, including lipoproteins, that comprise human atherosclerotic plaques is currently beyond the scope of any available imaging techniques. Color and near-infrared fluorescent angioscopy (CFA and NIRFA, respectively) systems have been recently developed for molecular imaging of lipoproteins within the human coronary arterial wall ex vivo and/or in vivo. The author reviews recent findings on lipoprotein deposition in human coronary plaques obtained by these imaging techniques. Recent Findings: Using specific biomarkers, native pro-atherogenic substances such as oxidized low-density lipoprotein (ox-LDL), LDL, triglycerides (TG), apolipoprotein B-100 (ApoB-100), and lysophosphatidylcholine (LPC), and the anti-atherogenic substance such as high-density lipoprotein (HDL) were visualized by CFA, and LDL and cholesterol by NIRFA, in coronary plaques obtained from autopsy subjects. The relationship between incidence and plaque morphology differed for each substance. The incidence of ox-LDL and LDL on color fluorescence microscopy correlated well with that observed using immunohistochemical techniques. During coronary catheterization in patients, ox-LDL, LDL, and HDL in coronary plaques were visualized by CFA or NIRFA. Conclusions: Using CFA or NIRFA, the distribution of the major native pro-atherogenic and antiatherogenic lipoproteins and their components within human coronary plaques can be evaluated ex vivo and/or in vivo. Fluorescent angioscopy could help our understanding of the molecular mechanisms of coronary atherosclerosis and in the evaluation of the effects of therapy targeting the substances comprising atherosclerotic coronary plaques. PMID:28381766

Relationship Between Central and Peripheral Atherosclerosis and Left Ventricular Dysfunction in a Community Population

PubMed Central

Tsao, Connie W.; Gona, Philimon; Salton, Carol; Murabito, Joanne M.; Oyama, Noriko; Danias, Peter G.; O’Donnell, Christopher J.; Manning, Warren J.; Yeon, Susan B.

2011-01-01

We aimed to determine the relationships between resting left ventricular (LV) wall motion abnormalities (WMAs), aortic plaque, and PAD in a community cohort. 1726 Framingham Heart Study Offspring Cohort participants (806 males, 65±9 years) underwent cardiovascular magnetic resonance with quantification of aortic plaque volume and assessment of regional LV systolic function. Claudication, lower extremity revascularization, and ankle-brachial index (ABI) were recorded at Examination 7. WMAs were associated with greater aortic plaque burden, decreased ABI, and claudication in age- and sex-adjusted analyses (all p<0.001), which were not significant after adjustment for cardiovascular risk factors. In age- and sex-adjusted analyses, both the presence (p<0.001) and volume of aortic plaque were associated with decreased ABI (p<0.001). After multivariable adjustment, ABI≤0.9 or prior revascularization was associated with a three-fold odds of aortic plaque (p=0.0083). Plaque volume significantly increased with decreasing ABI in multivariable-adjusted analyses (p<0.0001). In this free-living population, associations of WMAs with aortic plaque burden and clinical measures of PAD were attenuated after adjustment for coronary heart disease risk factors. Aortic plaque volume and ABI remained strongly negatively correlated after multivariable adjustment. Our findings suggest that the association between coronary heart disease and non-coronary atherosclerosis is explained by cardiovascular risk factors. Aortic atherosclerosis and PAD remain strongly associated after multivariable adjustment suggesting shared mechanisms beyond those captured by traditional risk factors. PMID:21708875

Effect of baking soda in dentifrices on plaque removal.

PubMed

Myneni, Srinivas R

2017-11-01

The prevention of dental caries and periodontal diseases targets control of dental plaque biofilm. In this context, chemical agents could represent a valuable complement to mechanical plaque control by reducing and controlling biofilm formation. The literature on the effectiveness of different dentifrices has not, however, been carefully categorized. A lack of consensus exists among dental professionals on a recommendation for a universal dentifrice for plaque control. The authors reviewed the scientific data on the different properties of sodium bicarbonate (baking soda)-containing dentifrices and their effectiveness in plaque removal. The results of the literature search show that baking soda-containing dentifrices are ideal candidates to be considered as a universal dentifrice because baking soda is inexpensive, abundant in supply, highly biocompatible, exhibits specific antibacterial properties to oral microorganisms, has low abrasivity, and is effective in plaque biofilm removal. Although some patients may benefit from desensitizing or high fluoride-containing dentifrices, those with routine needs may find using dentifrices containing baking soda and fluoride effective. Baking soda and fluoride dentifrices, therefore, may perhaps be considered as a criterion standard for patients with routine oral hygiene needs. Copyright © 2017 American Dental Association. Published by Elsevier Inc. All rights reserved.

Detection of Aβ plaque-associated astrogliosis in Alzheimer's disease brain by spectroscopic imaging and immunohistochemistry† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7an01747b

PubMed Central

Tamagnini, Francesco; Jeynes, J. Charles G.; Mattana, Sara; Swift, Imogen; Nallala, Jayakrupakar; Hancock, Jane; Brown, Jonathan T.; Randall, Andrew D.; Stone, Nick

2018-01-01

Recent work using micro-Fourier transform infrared (μFTIR) imaging has revealed that a lipid-rich layer surrounds many plaques in post-mortem Alzheimer's brain. However, the origin of this lipid layer is not known, nor is its role in the pathogenesis of Alzheimer's disease (AD). Here, we studied the biochemistry of plaques in situ using a model of AD. We combined FTIR, Raman and immunofluorescence images, showing that astrocyte processes co-localise with the lipid ring surrounding many plaques. We used μFTIR imaging to rapidly measure chemical signatures of plaques over large fields of view, and selected plaques for higher resolution analysis with Raman microscopy. Raman maps showed similar lipid rings and dense protein cores as in FTIR images, but also revealed cell bodies. We confirmed the presence of plaques using amylo-glo staining, and detected astrocytes using immunohistochemistry, revealing astrocyte co-localisation with lipid rings. This work is important because it correlates biochemical changes surrounding the plaque with the biological process of astrogliosis. PMID:29230441

Neutrophil Response to Dental Plaque by Gender and Race

PubMed Central

Wahaidi, V.Y.; Dowsett, S.A.; Eckert, G.J.; Kowolik, M.J.

2009-01-01

The inflammatory response, which has both genetic and environmental components, is a central mechanism linking oral and systemic diseases. We hypothesized that dental plaque accumulation over 21 days in the experimental gingivitis model would elicit systemic inflammatory responses [change in white blood cell (WBC) count and neutrophil activity], and that these responses would differ by gender/race. We recruited 156 healthy young adults, including black and white males and females. Plaque Index (PI), Gingival Index (GI), systemic WBC counts, and peripheral neutrophil oxidative activity were recorded. Overall, 128 participants completed the study. During the experimental phase, the correlation between PI and GI was 0.79. Total WBC and neutrophil counts did not change. Neutrophil activity increased in blacks but not whites, suggesting that there may be racial differences in the inflammatory response to dental plaque accumulation. PMID:19734456

Ischemic Stroke Patients Demonstrate Increased Carotid Plaque Microvasculature Compared to (Ocular) Transient Ischemic Attack Patients

PubMed Central

van Hoof, Raf H.M.; Schreuder, Floris H.B.M.; Nelemans, Patty; Truijman, Martine T.B.; van Orshoven, Narender P.; Schreuder, Tobien H.; Mess, Werner H.; Heeneman, Sylvia; van Oostenbrugge, Robert J.; Wildberger, Joachim E.; Kooi, M. Eline

2017-01-01

Background Patients with a recent ischemic stroke have a higher risk of recurrent stroke compared to (ocular) transient ischemic attack (TIA) patients. Plaque microvasculature is considered as a feature of plaque vulnerability and can be quantified with carotid dynamic contrast-enhanced MRI (DCE-MRI). The purpose of this cross-sectional study was to explore the association between plaque microvasculature and the type of recent cerebrovascular events in symptomatic patients with mild-to-moderate carotid stenosis. Methods A total of 87 symptomatic patients with a recent stroke (n = 35) or (ocular) TIA (n = 52) underwent carotid DCE-MRI examination. Plaque microvasculature was studied in the vessel wall and adventitia using DCE-MRI and the pharmacokinetic modeling parameter Ktrans. Statistical analysis was performed with logistic regression, correcting for associated clinical risk factors. Results The 75th percentile adventitial (OR 1.97, 95% CI 1.18–3.29) Ktrans was significantly associated with a recent ischemic stroke compared to (ocular) TIA in multivariate analysis, while clinical risk factors were not significantly associated with the type of event. Conclusions This study indicates a positive association of leaky plaque microvasculature with a recent ischemic stroke compared to (ocular) TIA. Prospective longitudinal studies are needed to investigate whether Ktrans or other plaque characteristics may serve as an imaging marker for predicting (the type of) future cerebrovascular events. PMID:28946147

Carotid plaque characterization using CT and MRI scans for synergistic image analysis

NASA Astrophysics Data System (ADS)

Getzin, Matthew; Xu, Yiqin; Rao, Arhant; Madi, Saaussan; Bahadur, Ali; Lennartz, Michelle R.; Wang, Ge

2014-09-01

Noninvasive determination of plaque vulnerability has been a holy grail of medical imaging. Despite advances in tomographic technologies , there is currently no effective way to identify vulnerable atherosclerotic plaques with high sensitivity and specificity. Computed tomography (CT) and magnetic resonance imaging (MRI) are widely used, but neither provides sufficient information of plaque properties. Thus, we are motivated to combine CT and MRI imaging to determine if the composite information can better reflect the histological determination of plaque vulnerability. Two human endarterectomy specimens (1 symptomatic carotid and 1 stable femoral) were imaged using Scanco Medical Viva CT40 and Bruker Pharmascan 16cm 7T Horizontal MRI / MRS systems. μCT scans were done at 55 kVp and tube current of 70 mA. Samples underwent RARE-VTR and MSME pulse sequences to measure T1, T2 values, and proton density. The specimens were processed for histology and scored for vulnerability using the American Heart Association criteria. Single modality-based analyses were performed through segmentation of key imaging biomarkers (i.e. calcification and lumen), image registration, measurement of fibrous capsule, and multi-component T1 and T2 decay modeling. Feature differences were analyzed between the unstable and stable controls, symptomatic carotid and femoral plaque, respectively. By building on the techniques used in this study, synergistic CT+MRI analysis may provide a promising solution for plaque characterization in vivo.

A Quantitative Model of Early Atherosclerotic Plaques Parameterized Using In Vitro Experiments.

PubMed

Thon, Moritz P; Ford, Hugh Z; Gee, Michael W; Myerscough, Mary R

2018-01-01

There are a growing number of studies that model immunological processes in the artery wall that lead to the development of atherosclerotic plaques. However, few of these models use parameters that are obtained from experimental data even though data-driven models are vital if mathematical models are to become clinically relevant. We present the development and analysis of a quantitative mathematical model for the coupled inflammatory, lipid and macrophage dynamics in early atherosclerotic plaques. Our modeling approach is similar to the biologists' experimental approach where the bigger picture of atherosclerosis is put together from many smaller observations and findings from in vitro experiments. We first develop a series of three simpler submodels which are least-squares fitted to various in vitro experimental results from the literature. Subsequently, we use these three submodels to construct a quantitative model of the development of early atherosclerotic plaques. We perform a local sensitivity analysis of the model with respect to its parameters that identifies critical parameters and processes. Further, we present a systematic analysis of the long-term outcome of the model which produces a characterization of the stability of model plaques based on the rates of recruitment of low-density lipoproteins, high-density lipoproteins and macrophages. The analysis of the model suggests that further experimental work quantifying the different fates of macrophages as a function of cholesterol load and the balance between free cholesterol and cholesterol ester inside macrophages may give valuable insight into long-term atherosclerotic plaque outcomes. This model is an important step toward models applicable in a clinical setting.

Automatic segmentation and 3D reconstruction of intravascular ultrasound images for a fast preliminar evaluation of vessel pathologies.

PubMed

Sanz-Requena, Roberto; Moratal, David; García-Sánchez, Diego Ramón; Bodí, Vicente; Rieta, José Joaquín; Sanchis, Juan Manuel

2007-03-01

Intravascular ultrasound (IVUS) imaging is used along with X-ray coronary angiography to detect vessel pathologies. Manual analysis of IVUS images is slow and time-consuming and it is not feasible for clinical purposes. A semi-automated method is proposed to generate 3D reconstructions from IVUS video sequences, so that a fast diagnose can be easily done, quantifying plaque length and severity as well as plaque volume of the vessels under study. The methodology described in this work has four steps: a pre-processing of IVUS images, a segmentation of media-adventitia contour, a detection of intima and plaque and a 3D reconstruction of the vessel. Preprocessing is intended to remove noise from the images without blurring the edges. Segmentation of media-adventitia contour is achieved using active contours (snakes). In particular, we use the gradient vector flow (GVF) as external force for the snakes. The detection of lumen border is obtained taking into account gray-level information of the inner part of the previously detected contours. A knowledge-based approach is used to determine which level of gray corresponds statistically to the different regions of interest: intima, plaque and lumen. The catheter region is automatically discarded. An estimate of plaque type is also given. Finally, 3D reconstruction of all detected regions is made. The suitability of this methodology has been verified for the analysis and visualization of plaque length, stenosis severity, automatic detection of the most problematic regions, calculus of plaque volumes and a preliminary estimation of plaque type obtaining for automatic measures of lumen and vessel area an average error smaller than 1mm(2) (equivalent aproximately to 10% of the average measure), for calculus of plaque and lumen volume errors smaller than 0.5mm(3) (equivalent approximately to 20% of the average measure) and for plaque type estimates a mismatch of less than 8% in the analysed frames.

Efficacy of Statin Therapy in Inducing Coronary Plaque Regression in Patients with Low Baseline Cholesterol Levels

PubMed Central

Nozue, Tsuyoshi; Yamamoto, Shingo; Tohyama, Shinichi; Fukui, Kazuki; Umezawa, Shigeo; Onishi, Yuko; Kunishima, Tomoyuki; Sato, Akira; Miyake, Shogo; Morino, Yoshihiro; Yamauchi, Takao; Muramatsu, Toshiya; Hibi, Kiyoshi; Terashima, Mitsuyasu; Suzuki, Hiroshi; Michishita, Ichiro

2016-01-01

Aim: The efficacy of statin therapy in inducing coronary plaque regression may depend on baseline cholesterol levels. We aimed to determine the efficacy of statin therapy in inducing coronary plaque regression in statin-naïve patients with low cholesterol levels using serial intravascular ultrasound (IVUS) data from the treatment with statin on atheroma regression evaluated by virtual histology IVUS (TRUTH) study. Methods: The TRUTH study is a prospective, multicenter trial, comparing the efficacies of pitavastatin and pravastatin in coronary plaque regression in 164 patients. All patients were statin-naïve and received statin therapy only after study enrollment. The primary endpoint was the observation of coronary plaque progression, despite statin therapy. Results: Serial IVUS data, at baseline and after an 8-month follow-up, were available for 119 patients. The patients were divided into three groups based on non-high-density lipoprotein cholesterol (HDL-C) levels—low: ≤ 140 mg/dl, n = 38; moderate: 141–169 mg/dl, n = 42; and high: ≥ 170 mg/dl, n = 39. Coronary plaque progression was noted in the low cholesterol group, whereas plaque regression was noted in the moderate and high cholesterol groups [%Δplaque volume: 2.3 ± 7.4 vs. − 2.7 ± 10.7 vs. − 3.2 ± 7.5, p = 0.004 (analysis of variance)]. After adjusting for all variables, a low non-HDLC level (≤ 140 mg/dl) was identified as an independent predictor of coronary plaque progression [odds ratio, 3.7; 95% confidence interval, 1.5–9.1, p = 0.004]. Conclusion: Serial IVUS data analysis indicated that statin therapy was less effective in inducing coronary plaque regression in patients with low cholesterol levels but more effective in those with high cholesterol levels at baseline. University Hospital Medical Information Network (UMIN) (UMIN ID: C000000311). PMID:27040362

[Dental plaque microcosm biofilm behavior on a resin composite incorporated with nano-antibacterial inorganic filler containing long-chain alkyl quaternary ammonium salt].

PubMed

Junling, Wu; Qiang, Zhang; Ruinan, Sun; Ting, Zhu; Jianhua, Ge; Chuanjian, Zhou

2015-12-01

To develop a resin composite incorporated with nano-antibacterial inorganic filler containing long-chain alkyl quaternary ammonium salt, and to measure its effect on human dental plaque microcosm biofilm. A novel nano-antibacterial inorganic filler containing long-chain alkyl quaternary ammonium salt was synthesized according to methods introduced in previous research. Samples of the novel nano-antibacterial inorganic fillers were modified by a coupling agent and then added into resin composite at 0%, 5%, 10%, 15% or 20% mass fractions; 0% composite was used as control. A flexural test was used to measure resin composite mechanical properties. Results showed that a dental plaque microcosm biofilm model with human saliva as inoculum was formed. Colony-forming unit (CFU) counts, lactic acid production, and live/dead assay of biofilm on the resin composite were calculated to test the effect of the resin composite on human dental plaque microcosm biofilm. The incorporation of nano-antibacterial inorganic fillers with as much as 15% concentration into the resin composite showed no adverse effect on the mechanical properties of the resin composite (P > 0.05). Resin composite containing 5% or more nano-antibacterial inorganic fillers significantly inhibited the metabolic activity of dental plaque microcosm biofilm, suggesting its strong antibacterial potency (P < 0.05). This novel resin composite exhibited a strong antibacterial property upon the addition of up to 5% nano-antibacterial inorganic fillers, thereby leading to effective caries inhibition in dental application.

Increased popliteal circumferential wall tension induced by orthostatic body posture is associated with local atherosclerotic plaques.

PubMed

Gemignani, Tiago; Azevedo, Renata C; Higa, Celina M; Coelho, Otávio R; Matos-Souza, José R; Nadruz, Wilson

2012-09-01

Lower limb arteries are exposed to higher hemodynamic burden in erectile posture. This study evaluated the effects of body posture on popliteal, carotid and brachial circumferential wall tension (CWT) and investigated the relationship between local CWT and atherosclerotic plaques in subjects with cardiovascular risk factors. Two hundred and three subjects (118 women and 85 men) with cardiovascular risk factors (smoking, hypertension or diabetes mellitus) underwent clinical and laboratory analysis and had their blood pressure measured in the arm and calf in supine and orthostatic positions. Arteries were evaluated by ultrasound analysis, while CWT was calculated according to Laplace's law. Among the enrolled participants, 47%, 29% and none presented popliteal, carotid and brachial plaques, respectively. Carotid CWT measurements were not associated with local plaques after adjustment for potential confounders. Conversely, general linear model and logistic regression analyses adjusted for potential confounders demonstrated that peak orthostatic CWT was the only local hemodynamic parameter showing significant relationship with popliteal plaques in the whole sample. In gender-specific analyses, although positively correlated with popliteal plaques in both genders, local peak orthostatic CWT exhibited an independent association with popliteal plaques after adjustment for potential confounders only in women. Popliteal CWT measured in orthostatic posture, rather than in supine position, is associated with popliteal atherosclerotic plaques, particularly in women. These findings suggest that erectile posture might play a role in the atherogenesis of leg arteries by modifying local hemodynamic forces and that there may be gender differences in this regard. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Shedding Light on the Molecular Pathology of Amyloid Plaques in Transgenic Alzheimer's Disease Mice Using Multimodal MALDI Imaging Mass Spectrometry.

PubMed

Kaya, Ibrahim; Zetterberg, Henrik; Blennow, Kaj; Hanrieder, Jörg

2018-05-04

Senile plaques formed by aggregated amyloid β peptides are one of the major pathological hallmarks of Alzheimer's disease (AD) which have been suggested to be the primary influence triggering the AD pathogenesis and the rest of the disease process. However, neurotoxic Aβ aggregation and progression are associated with a wide range of enigmatic biochemical, biophysical and genetic processes. MALDI imaging mass spectrometry (IMS) is a label-free method to elucidate the spatial distribution patterns of intact molecules in biological tissue sections. In this communication, we utilized multimodal MALDI-IMS analysis on 18 month old transgenic AD mice (tgArcSwe) brain tissue sections to enhance molecular information correlated to individual amyloid aggregates on the very same tissue section. Dual polarity MALDI-IMS analysis of lipids on the same pixel points revealed high throughput lipid molecular information including sphingolipids, phospholipids, and lysophospholipids which can be correlated to the ion images of individual amyloid β peptide isoforms at high spatial resolutions (10 μm). Further, multivariate image analysis was applied in order to probe the multimodal MALDI-IMS data in an unbiased way which verified the correlative accumulations of lipid species with dual polarity and Aβ peptides. This was followed by the lipid fragmentation obtained directly on plaque aggregates at higher laser pulse energies which provided tandem MS information useful for structural elucidation of several lipid species. Majority of the amyloid plaque-associated alterations of lipid species are for the first time reported here. The significance of this technique is that it allows correlating the biological discussion of all detected plaque-associated molecules to the very same individual amyloid plaques which can give novel insights into the molecular pathology of even a single amyloid plaque microenvironment in a specific brain region. Therefore, this allowed us to interpret the possible roles of lipids and amyloid peptides in amyloid plaque-associated pathological events such as focal demyelination, autophagic/lysosomal dysfunction, astrogliosis, inflammation, oxidative stress, and cell death.

Do radial oxygen loss and external aeration affect iron plaque formation and arsenic accumulation and speciation in rice?

PubMed Central

Wu, Chuan; Ye, Zhihong; Li, Hui; Wu, Shengchun; Deng, Dan; Zhu, Yongguan; Wong, Minghung

2012-01-01

Hydroponic experiments were conducted to investigate the effect of radial oxygen loss (ROL) and external aeration on iron (Fe) plaque formation, and arsenic (As) accumulation and speciation in rice (Oryza sativa L.). The data showed that there were significant correlations between ROL and Fe concentrations in Fe plaque produced on different genotypes of rice. There were also significant differences in the amounts of Fe plaque formed between different genotypes in different positions of roots and under different aeration conditions (aerated, normal, and stagnant treatments). In aerated treatments, rice tended to have a higher Fe plaque formation than in a stagnant solution, with the greatest formation at the root tip decreasing with increasing distances away, in accordance with a trend of spatial ROL. Genotypes with higher rates of ROL induced higher degrees of Fe plaque formation. Plaques sequestered As on rice roots, with arsenate almost double that with arsenite, leading to decreased As accumulation in both roots and shoots. The major As species detected in roots and shoots was arsenite, ranging from 34 to 78% of the total As in the different treatments and genotypes. These results contribute to our understanding of genotypic differences in As uptake by rice and the mechanisms causing rice genotypes with higher ROL to show lower overall As accumulation. PMID:22345639

Effectiveness of erythrosine-mediated photodynamic antimicrobial chemotherapy on dental plaque aerobic microorganisms: A randomized controlled trial.

PubMed

Bhat, Manohar; Acharya, Swathi; Prasad, Kakarla Veera Venkata; Kulkarni, Raghavendra; Bhat, Anithraj; Bhat, Devikripa

2017-01-01

Dental plaque is one of the predominant causes of major oral diseases. Although mechanical and chemical methods are extensively followed to control the development of plaque, plaque-related diseases still persist. Therefore, this necessitates for alternative measures of plaque control, one such alternative is photodynamic antimicrobial chemotherapy (PACT). Split mouth randomized clinical trial (CTRI/2017/03/008239) was conducted on 30 participants who reported to the hospital. Participants were asked to rinse their mouth for 1 min using 10 ml of 25 μM erythrosine solutions. Same tooth on both quadrants of the same jaw are selected as the test and control. Intervention used was halogen-based composite curing light with wavelength of 500-590 nm. Plaque sample from the control tooth and test tooth was collected before and after exposure, respectively, and sent to microbiological laboratory for colony count. Logarithmic mean and standard deviation of control group with 10 2 dilutions of aerobic microbial count were found to be 5.34 ± 0.94, and for experimental group, it was 4.47 ± 1.37. The statistical difference between mean CFU values between aerobic bacterial counts was significant ( P = 0.006). Erythrosine-mediated PACT reduces the extent of dental plaque microbial count and has a potential preventive and therapeutic use in day-to-day life and dental clinics.

Matrix vesicles in the fibrous cap of atherosclerotic plaque: possible contribution to plaque rupture

PubMed Central

Bobryshev, Y V; Killingsworth, M C; Lord, R S A; Grabs, A J

2008-01-01

Plaque rupture is the most common type of plaque complication and leads to acute ischaemic events such as myocardial infarction and stroke. Calcification has been suggested as a possible indicator of plaque instability. Although the role of matrix vesicles in the initial stages of arterial calcification has been recognized, no studies have yet been carried out to examine a possible role of matrix vesicles in plaque destabilization. Tissue specimens selected for the present study represented carotid specimens obtained from patients undergoing carotid endarterectomy. Serial frozen cross-sections of the tissue specimens were cut and mounted on glass slides. The thickness of the fibrous cap (FCT) in each advanced atherosclerotic lesion, containing a well developed lipid/necrotic core, was measured at its narrowest sites in sets of serial sections. According to established criteria, atherosclerotic plaque specimens were histologically subdivided into two groups: vulnerable plaques with thin fibrous caps (FCT <100 μm) and presumably stable plaques, in which fibrous caps were thicker than 100 μm. Twenty-four carotid plaques (12 vulnerable and 12 presumably stable plaques) were collected for the present analysis of matrix vesicles in fibrous caps. In order to provide a sufficient number of representative areas from each plaque, laser capture microdissection (LCM) was carried out. The quantification of matrix vesicles in ultrathin sections of vulnerable and stable plaques revealed that the numbers of matrix vesicles were significantly higher in fibrous caps of vulnerable plaques than those in stable plaques (8.908±0.544 versus 6.208±0.467 matrix vesicles per 1.92 μm2 standard area; P= 0.0002). Electron microscopy combined with X-ray elemental microanalysis showed that some matrix vesicles in atherosclerotic plaques were undergoing calcification and were characterized by a high content of calcium and phosphorus. The percentage of calcified matrix vesicles/microcalcifications was significantly higher in fibrous caps in vulnerable plaques compared with that in stable plaques (6.705±0.436 versus 5.322±0A94; P= 0.0474). The findings reinforce a view that the texture of the extracellular matrix in the thinning fibrous cap of atherosclerotic plaque is altered and this might contribute to plaque destabilization. PMID:18194456

A four-week clinical study to evaluate and compare the effectiveness of a baking soda dentifrice and an antimicrobial dentifrice in reducing plaque.

PubMed

Ghassemi, Annahita; Vorwerk, Linda M; Hooper, William J; Putt, Mark S; Milleman, Kimberly R

2008-01-01

To evaluate and compare the effectiveness in reducing plaque of a fluoride dentifrice containing baking soda and a non-baking soda fluoride dentifrice containing an antimicrobial (triclosan/copolymer) system after a single brushing and over a four-week period of daily brushing. A total of 207 subjects completed this randomized, blinded, parallel-group clinical study. Twenty-four hour plaque buildup was scored at baseline and after two and four weeks of twice-daily use of the products. Additionally, controlled single brushing with the assigned dentifrice, followed by post-brushing plaque assessment, was performed at the start (baseline visit) and end (Week-4 visit) of the study. Plaque was scored using the Turesky, et al. modification of Quigley-Hein Index at six sites per tooth, according to Soparkar's modification. Mean baseline whole mouth plaque scores for the baking soda and triclosan dentifrice groups were 2.90 +/- 0.40 and 2.90 +/- 0.39, respectively, and the difference was not statistically significant. Within-group analysis showed that both products significantly reduced the amount of plaque over the four-week period (p < 0.001). Between-group analysis showed that brushing with the baking soda dentifrice exhibited significantly greater reduction in plaque scores (p < 0.001) after two and four weeks of brushing as compared to the triclosan dentifrice. After four weeks, the mean plaque reduction for the baking soda dentifrice group (0.34 +/- 0.32) was 2.22-fold greater than that observed for the triclosan dentifrice group (0.15 +/- 0.24). Similarly, single brushing with the baking soda dentifrice showed a 1.88- to 2.08-fold greater pre- to post-brushing plaque difference as compared to the triclosan dentifrice at the baseline visit (mean plaque reduction: baking soda 0.54 +/- 0.26; triclosan 0.28 +/- 0.18; ratio 1.88X) and Week-4 visit (baking soda 0.47 +/- 0.21; triclosan 0.23 +/- 0.15; ratio 2.08X). Similar to the whole mouth scores, evaluation of various tooth sites (facial, lingual, proximal, and gingival) showed a significantly greater reduction in plaque scores for brushing with the baking soda dentifrice as compared to brushing with the triclosan dentifrice. The results of this study indicate that the baking soda dentifrice was more effective than the non-baking soda, antimicrobial dentifrice in plaque removal after a single tooth brushing, and in maintaining significantly lower plaque levels during a four-week period of twice daily, unsupervised tooth brushing.

Plaque shift and distal embolism in patients with acute myocardial infarction: a volumetric intravascular ultrasound analysis from the HORIZONS-AMI trial.

PubMed

Wu, Xiaofan; Maehara, Akiko; He, Yong; Xu, Kai; Oviedo, Carlos; Witzenbichler, Bernhard; Lansky, Alexandra J; Dressler, Ovidiu; Parise, Helen; Stone, Gregg W; Mintz, Gary S

2013-08-01

Vessel expansion and axial plaque redistribution or distal plaque embolization contribute to the increase in lumen dimensions after stent implantation. Preintervention and postintervention grayscale volumetric intravascular ultrasound was used to study 43 de novo native coronary lesions treated with TAXUS or Express bare metal stents in the HORIZONS-AMI Trial. There was a decrease in lesion segment plaque + media (P + M) volume (-19.5 ± 22.2 mm(3) ) that was associated with a decrease in overall analysis segment (lesion plus 5 mm long proximal and distal reference segments) P + M volume (-17.5 ± 21.0 mm(3) ) that was greater than the shift of plaque from the lesion to the proximal and distal reference segments (1.9 ± 4.5 mm(3) , P < 0.0001). Overall analysis segment P + M volume decreased more in the angiographic thrombus (+) versus the thrombus (-) group (27.4 ± 23.4 vs. -8.9 ± 14.3 mm(3) , P = 0.003), whereas plaque shift to the reference segments showed no significant difference between the two groups (1.5 ± 5.2 vs. 2.3 ± 3.9 mm(3) , P = 0.590). Compared with the angiographic thrombus (-) group, patients in the thrombus (+) group more often developed no reflow (25% vs. 0%, P = 0.012) and had a higher preintervention CK-MB (P = 0.011), postintervention CK-MB (P < 0.001), and periprocedural (post-PCI minus pre-PCI) elevation of CK-MB (P = 0.001). In acute myocardial infarction lesions, there was a marked poststenting reduction in overall plaque volume that was significantly greater in patients with angiographic thrombus than without thrombus and may have explained a greater periprocedural rise in CK-MB. © 2013 Wiley Periodicals, Inc.

Interactions among variants in TXA2R, P2Y12 and GPIIIa are associated with carotid plaque vulnerability in Chinese population.

PubMed

Yi, Xingyang; Lin, Jing; Luo, Hua; Zhou, Ju; Zhou, Qiang; Wang, Yanfen; Wang, Chun

2018-04-03

The associations between variants in platelet activation-relevant genes and carotid plaque vulnerability are not fully understood. The aim of the present study was to investigate the associations of the variants in platelet activation-relevant genes and interactions among these variants with carotid plaque vulnerability. There were no significant differences in the frequencies of genotypes of the 11 variants between patients and controls. Among 396 patients, 102 patients had not carotid plaque, 106 had VP, and 188 had SP. The 11 variants were not independently associated with risk of carotid plaque vulnerability after adjusting for potential confounding variables. However, the GMDR analysis showed that there were synergistic effects of gene-gene interactions among TXA2Rr s1131882, GPIIIa rs2317676 and P2Y12 rs16863323 on carotid plaque vulnerability. The high-risk interactions among the three variants were associated with high platelet activation, and independently associated with the risk of carotid plaque vulnerability. Eleven variants in platelet activation-relevant genes were examined using mass spectrometry methods in 396 ischemic stroke patients and 291controls. Platelet-leukocyte aggregates and platelet aggregation were also measured. Carotid plaques were assessed by B-mode ultrasound. According to the results of ultrasound, the patients were stratified into three groups: non-plaque group, vulnerable plaque (VP) group and stable plaque (SP) group. Furthermore, gene-gene interactions were analyzed using generalized multifactor dimensionality reduction (GMDR) methods. The rs1131882, rs2317676, and rs16863323 three-loci interactions may confer a higher risk of carotid plaque vulnerability, and might be potential markers for plaque instability.

Validation of Noninvasive In Vivo Compound Ultrasound Strain Imaging Using Histologic Plaque Vulnerability Features.

PubMed

Hansen, Hendrik H G; de Borst, Gert Jan; Bots, Michiel L; Moll, Frans L; Pasterkamp, Gerard; de Korte, Chris L

2016-11-01

Carotid plaque rupture is a major cause of stroke. Key issue for risk stratification is early identification of rupture-prone plaques. A noninvasive technique, compound ultrasound strain imaging, was developed providing high-resolution radial deformation/strain images of atherosclerotic plaques. This study aims at in vivo validation of compound ultrasound strain imaging in patients by relating the measured strains to typical features of vulnerable plaques derived from histology after carotid endarterectomy. Strains were measured in 34 severely stenotic (>70%) carotid arteries at the culprit lesion site within 48 hours before carotid endarterectomy. In all cases, the lumen-wall boundary was identifiable on B-mode ultrasound, and the imaged cross-section did not move out of the imaging plane from systole to diastole. After endarterectomy, the plaques were processed using a validated histology analysis technique. Locally elevated strain values were observed in regions containing predominantly components related to plaque vulnerability, whereas lower values were observed in fibrous, collagen-rich plaques. The median strain of the inner plaque layer (1 mm thickness) was significantly higher (P<0.01) for (fibro)atheromatous (n=20, strain=0.27%) than that for fibrous plaques (n=14, strain=-0.75%). Also, a significantly larger area percentage of the inner layer revealed strains above 0.5% for (fibro)atheromatous (45.30%) compared with fibrous plaques (31.59%). (Fibro)atheromatous plaques were detected with a sensitivity, specificity, positive predictive value, and negative predictive value of 75%, 86%, 88%, and 71%, respectively. Strain did not significantly correlate with fibrous cap thickness, smooth muscle cell, or macrophage concentration. Compound ultrasound strain imaging allows differentiating (fibro)atheromatous from fibrous carotid artery plaques. © 2016 American Heart Association, Inc.

Comparative effect of chewing sticks and toothbrushing on plaque removal and gingival health.

PubMed

Al-Otaibi, Meshari; Al-Harthy, Mohammed; Söder, Birgitta; Gustafsson, Anders; Angmar-Månsson, Birgit

2003-01-01

The aim of the study was to compare the effect of the chewing stick (miswak), and toothbrushing on plaque removal and gingival health. The participants comprised 15 healthy Saudi Arabian male volunteers aged 21 to 36 years, attending the Dental Center at Al-Noor Specialist Hospital in Makkah City in Saudi Arabia. The study was designed as a single, blind, randomized crossover study. The Turesky modified Quigley-Hein plaque and Löe-Silness gingival indices and digital photographs of plaque distribution were recorded at baseline, one week after professional tooth cleaning, and again following three weeks use of either the miswak or toothbrush. Professional tooth cleaning was repeated, and after a further three weeks use of either the miswak or toothbrush (using the alternative method to that used in the first experimental period), plaque and gingival indices, and digital photographs of plaque distribution were recorded anew. Compared to toothbrushing, the use of the miswak resulted in significant reductions in plaque (p < 0.001) and gingival (p < 0.01) indices. Image analysis of the plaque distribution showed a significant difference in reduction of plaque between the miswak and toothbrush periods (p < 0.05). It is concluded that the miswak is more effective than toothbrushing for reducing plaque and gingivitis, when preceded by professional instruction in its correct application. The miswak appeared to be more effective than toothbrushing for removing plaque from the embrasures, thus enhancing interproximal health.

Template-directed deposition of amyloid

NASA Astrophysics Data System (ADS)

Ha, Chanki

The formation of amyloid plaques in tissue is a pathological feature of many neurodegenerative diseases. Amyloid deposition, the process of amyloid plaque growth by the association of individual soluble amyloid molecules with a pre-existing amyloid template (i.e. plaque), is known to be critical for amyloid formation in vivo. In order to characterize amyloid deposition, we developed novel, synthetic amyloid templates like amyloid plaques in the human Alzheimer's brain by attaching amyloid seeds covalently onto an N-hydroxysuccinimide-activated surface. Amyloid plaques with a characteristic beta-sheet structure formed through a conformational rearrangement of soluble insulin or Abeta monomers upon interaction with the template. The amyloid deposition rate followed saturation kinetics with respect to insulin concentration in the solution. According to visualization of temporal evolution of Abeta plaque deposition on a template, it was found that mature amyloid plaques serve as a sink of soluble Abeta in a solution as well as a reservoir of small aggregates such as oligomers and protofibrils. Quantitative analysis of seeding efficiencies of three different Abeta species revealed that oligomeric forms of Abeta act more efficiently as seeds than monomers or fibrils do. Furthermore, studies on the interaction between Abeta40 and 42 showed an important role of Abeta42 in amyloid deposition. A slightly acidic condition was found to be unfavorable for amyloid plaque formation. Effects of metal ions on amyloid deposition indicated that Fe3+, but not Cu3 and Zn2+, is important for the deposition of amyloid plaques. The binding of Fe3+ to Abeta42 peptide was confirmed by using SIMS analysis. Zn2+ induced nonfibrillar amorphous aggregates, but the release of Zn2+ from Abeta42 deposits by Fe3+ triggered the formation of amyloid fibers. Effects or metal ion chelators such as ethylenediamine tetraacetic acid, deferoxamine, and clioquinol on amyloid deposition were tested to determine if they can be effective in preventing the deposition of amyloid plaques. The results may give insights into understanding the effects of environmental factors on amyloid plaque deposition and important information for therapeutic development for Alzheimer's disease.

18F-Fluoride and 18F-Fluorodeoxyglucose Positron Emission Tomography After Transient Ischemic Attack or Minor Ischemic Stroke

PubMed Central

Jenkins, William S. A.; Irkle, Agnese; Moss, Alastair; Sng, Greg; Forsythe, Rachael O.; Clark, Tim; Roberts, Gemma; Fletcher, Alison; Lucatelli, Christophe; Rudd, James H. F.; Davenport, Anthony P.; Mills, Nicholas L.; Al-Shahi Salman, Rustam; Dennis, Martin; Whiteley, William N.; van Beek, Edwin J. R.; Dweck, Marc R.; Newby, David E.

2017-01-01

Background— Combined positron emission tomography (PET) and computed tomography (CT) can assess both anatomy and biology of carotid atherosclerosis. We sought to assess whether 18F-fluoride or 18F-fluorodeoxyglucose can identify culprit and high-risk carotid plaque. Methods and Results— We performed 18F-fluoride and 18F-fluorodeoxyglucose PET/CT in 26 patients after recent transient ischemic attack or minor ischemic stroke: 18 patients with culprit carotid stenosis awaiting carotid endarterectomy and 8 controls without culprit carotid atheroma. We compared standardized uptake values in the clinically adjudicated culprit to the contralateral asymptomatic artery, and assessed the relationship between radiotracer uptake and plaque phenotype or predicted cardiovascular risk (ASSIGN score [Assessing Cardiovascular Risk Using SIGN Guidelines to Assign Preventive Treatment]). We also performed micro PET/CT and histological analysis of excised plaque. On histological and micro PET/CT analysis, 18F-fluoride selectively highlighted microcalcification. Carotid 18F-fluoride uptake was increased in clinically adjudicated culprit plaques compared with asymptomatic contralateral plaques (log10standardized uptake valuemean 0.29±0.10 versus 0.23±0.11, P=0.001) and compared with control patients (log10standardized uptake valuemean 0.29±0.10 versus 0.12±0.11, P=0.001). 18F-Fluoride uptake correlated with high-risk plaque features (remodeling index [r=0.53, P=0.003], plaque burden [r=0.51, P=0.004]), and predicted cardiovascular risk [r=0.65, P=0.002]). Carotid 18F-fluorodeoxyglucose uptake appeared to be increased in 7 of 16 culprit plaques, but no overall differences in uptake were observed in culprit versus contralateral plaques or control patients. However, 18F-fluorodeoxyglucose did correlate with predicted cardiovascular risk (r=0.53, P=0.019), but not with plaque phenotype. Conclusions— 18F-Fluoride PET/CT highlights culprit and phenotypically high-risk carotid plaque. This has the potential to improve risk stratification and selection of patients who may benefit from intervention. PMID:28292859

A direct vulnerable atherosclerotic plaque elasticity reconstruction method based on an original material-finite element formulation: theoretical framework

PubMed Central

Bouvier, Adeline; Deleaval, Flavien; Doyley, Marvin M; Yazdani, Saami K; Finet, Gérard; Le Floc'h, Simon; Cloutier, Guy; Pettigrew, Roderic I; Ohayon, Jacques

2016-01-01

The peak cap stress (PCS) amplitude is recognized as a biomechanical predictor of vulnerable plaque (VP) rupture. However, quantifying PCS in vivo remains a challenge since the stress depends on the plaque mechanical properties. In response, an iterative material finite element (FE) elasticity reconstruction method using strain measurements has been implemented for the solution of these inverse problems. Although this approach could resolve the mechanical characterization of VPs, it suffers from major limitations since (i) it is not adapted to characterize VPs exhibiting high material discontinuities between inclusions, and (ii) does not permit real time elasticity reconstruction for clinical use. The present theoretical study was therefore designed to develop a direct material-FE algorithm for elasticity reconstruction problems which accounts for material heterogeneities. We originally modified and adapted the extended FE method (Xfem), used mainly in crack analysis, to model material heterogeneities. This new algorithm was successfully applied to six coronary lesions of patients imaged in vivo with intravascular ultrasound. The results demonstrated that the mean relative absolute errors of the reconstructed Young's moduli obtained for the arterial wall, fibrosis, necrotic core, and calcified regions of the VPs decreased from 95.3±15.56%, 98.85±72.42%, 103.29±111.86% and 95.3±10.49%, respectively, to values smaller than 2.6 × 10−8±5.7 × 10−8% (i.e. close to the exact solutions) when including modified-Xfem method into our direct elasticity reconstruction method. PMID:24240392

Detection and characterization of early plaque formations by Raman probe spectroscopy and optical coherence tomography: an in vivo study on a rabbit model

NASA Astrophysics Data System (ADS)

Matthäus, Christian; Dochow, Sebastian; Egodage, Kokila D.; Romeike, Bernd F.; Brehm, Bernhard R.; Popp, Jürgen

2018-01-01

Intravascular imaging techniques provide detailed specification about plaque appearance and morphology, but cannot deliver information about the biochemical composition of atherosclerotic plaques. As the biochemical composition is related to the plaque type, important aspects such as the risk of a plaque rupture and treatment are still difficult to assess. Currently, various spectroscopic techniques are tested for potential applications for the chemical analysis of plaque depositions. Here, we employ Raman spectroscopy in combination with optical coherence tomography (OCT) for the characterization of plaques on rabbits in vivo. Experiments were carried out on New Zealand white rabbits treated with a fat- and cholesterol-enriched diet, using a Raman probe setup with a 785-nm multimode laser as an excitation source. Subsequently, OCT images were acquired with a swept source at 1305±55 nm at 22.6 mW. Raman spectra were recorded from normal regions and regions with early plaque formations. The probe positioning was monitored by x-ray angiography. The spectral information identified plaque depositions consisting of lipids, with triglycerides as the major component. Afterward, OCT images of the spectroscopically investigated areas were obtained. The spectral information correlates well with the observed intravascular morphology and is in good agreement with histology. Raman spectroscopy can provide detailed biochemical specification of atherosclerotic plaques.

Lytic and Chemotactic Features of the Plaque-Forming Bacterium KD531 on Phaeodactylum tricornutum

PubMed Central

Chen, Zhangran; Zheng, Wei; Yang, Luxi; Boughner, Lisa A.; Tian, Yun; Zheng, Tianling; Xu, Hong

2017-01-01

Phaeodactylum tricornutum is a dominant bloom forming species and potential biofuel feedstock. To control P. tricornutum bloom or to release lipids from P. tricornutum, we previously screened and identified the lytic bacterium Labrenzia sp. KD531 toward P. tricornutum. In the present study, we evaluated the lytic activity of Labrenzia sp. KD531 on microalgae and investigated its lytic mechanism. The results indicated that the lytic activity of KD531 was temperature- and pH-dependent, but light-independent. In addition to P. tricornutum, KD531 also showed lytic activity against other algal species, especially green algae. A quantitative analysis of algal cellular protein, carbohydrate and lipid content together with measurements of dry weight after exposure to bacteria-infected algal lysate indicated that the bacterium KD531 influenced the algal biomass by disrupting the algal cells. Both chemotactic analysis and microscopic observations of subsamples from different regions of formed plaques showed that KD531 could move toward and then directly contact algal cells. Direct contact between P. tricornutum and KD531 cells was essential for the lytic process. PMID:29312256

In Situ FTIR Microspectroscopy of Brain Tissue from a Transgenic Mouse Model of Alzheimer Disease

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

Rak,M.; Del Bigio, M.; Mai, S.

2007-01-01

Plaques composed of the A{beta} peptide are the main pathological feature of Alzheimer's disease. Dense-core plaques are fibrillar deposits of A{beta}, showing all the classical properties of amyloid including {beta}-sheet secondary structure, while diffuse plaques are amorphous deposits. We studied both plaque types, using synchrotron infrared (IR) microspectroscopy, a technique that allows the chemical composition and average protein secondary structure to be investigated in situ. We examined plaques in hippocampal, cortical and caudal tissue from 5- to 21-month-old TgCRND8 mice, a transgenic model expressing doubly mutant amyloid precursor protein, and displaying impaired hippocampal function and robust pathology from an earlymore » age. Spectral analysis confirmed that the congophilic plaque cores were composed of protein in a {beta}-sheet conformation. The amide I maximum of plaque cores was at 1623 cm-1, and unlike for in vitro A{beta} fibrils, the high-frequency (1680-1690 cm-1) component attributed to antiparallel {beta}-sheet was not observed. A significant elevation in phospholipids was found around dense-core plaques in TgCRND8 mice ranging in age from 5 to 21 months. In contrast, diffuse plaques were not associated with IR detectable changes in protein secondary structure or relative concentrations of any other tissue components.« less

Inhibition of Tongue Coat and Dental Plaque Formation by Stabilized Chlorine Dioxide Vs Chlorhexidine Mouthrinse: A Randomized, Triple Blinded Study.

PubMed

Yadav, Seema Roodmal; Kini, Vineet Vaman; Padhye, Ashvini

2015-09-01

Chlorine dioxide (ClO2) is an oxidizing agent with known bactericidal, viricidal and fungicidal properties. Its efficacy in reducing the halitosis has been established by previous literature. However, data evaluating its antiplaque property is scarce. Chlorhexidine (CHX) is considered as the gold standard and an effective adjunctive to mechanical plaque removal. However, it is associated with few reversible side effects. Therefore a study was conducted to assess the antiplaque property of ClO2 containing mouthrinse against CHX mouthrinse. To evaluate the efficacy of stabilized chlorine dioxide containing mouthrinse and CHX containing mouthrinse in inhibition of tongue coat accumulation and dental plaque formation using a four day plaque regrowth model clinically and microbiologically in a healthy dental cohort. A Single Center, Randomized, Triple blinded, Microbiological clinical trial was conducted involving 25 healthy dental students volunteers (11 males, 14 females). Two commercially available mouthrinse: Mouthrinse A - Aqueous based ClO2 mouthrinse Freshchlor(®) and Mouthrinse B - Aqueous based 0.2% CHX mouthrinse Hexidine(®) were selected as the test products. Subjects were asked to rinse and gargle for 1 minute with the allocated mouthrinse under supervision after supragingival scaling, polishing and tongue coat removal. After four hours, smears were taken from the buccal mucosa and tooth surface. On the fifth day from baseline of four day non brushing plaque regrowth model the samples were again taken from buccal mucosa and tooth surface followed by recording of plaque scores by Rastogi Modification of Navy Plaque index, extent of tongue coat by Winkel's tongue coating index and measuring tongue coat wet weight in grams. The samples collected were subjected to microbial analysis and the results were expressed as colony forming units (CFUs) per sample. The Data was analysed using SPSS 16.00 and presented using descriptive statistics. Independent t-test was used for the comparison between mouthrinse A groups & mouthrinse B group. The plaque scores and Winkels tongue coat scores, wet tongue coat weight recorded on the fifth day after the use of the two mouthrinse didn't show a statistically significant difference. The CFU per sample from tooth and mucosa after four hours revealed low bacteria count with respect to mouthrinse B however the CFU obtained on the fifth day did not show a statistically significant difference between the two mouthrinse. The clinical antiplaque efficacy of CHX and ClO2 mouthwash is comparable and so is the efficacy in reducing the oral bacterial load.

Software and Algorithms for Biomedical Image Data Processing and Visualization

NASA Technical Reports Server (NTRS)

Talukder, Ashit; Lambert, James; Lam, Raymond

2004-01-01

A new software equipped with novel image processing algorithms and graphical-user-interface (GUI) tools has been designed for automated analysis and processing of large amounts of biomedical image data. The software, called PlaqTrak, has been specifically used for analysis of plaque on teeth of patients. New algorithms have been developed and implemented to segment teeth of interest from surrounding gum, and a real-time image-based morphing procedure is used to automatically overlay a grid onto each segmented tooth. Pattern recognition methods are used to classify plaque from surrounding gum and enamel, while ignoring glare effects due to the reflection of camera light and ambient light from enamel regions. The PlaqTrak system integrates these components into a single software suite with an easy-to-use GUI (see Figure 1) that allows users to do an end-to-end run of a patient s record, including tooth segmentation of all teeth, grid morphing of each segmented tooth, and plaque classification of each tooth image. The automated and accurate processing of the captured images to segment each tooth [see Figure 2(a)] and then detect plaque on a tooth-by-tooth basis is a critical component of the PlaqTrak system to do clinical trials and analysis with minimal human intervention. These features offer distinct advantages over other competing systems that analyze groups of teeth or synthetic teeth. PlaqTrak divides each segmented tooth into eight regions using an advanced graphics morphing procedure [see results on a chipped tooth in Figure 2(b)], and a pattern recognition classifier is then used to locate plaque [red regions in Figure 2(d)] and enamel regions. The morphing allows analysis within regions of teeth, thereby facilitating detailed statistical analysis such as the amount of plaque present on the biting surfaces on teeth. This software system is applicable to a host of biomedical applications, such as cell analysis and life detection, or robotic applications, such as product inspection or assembly of parts in space and industry.

Successful Expansion of an Underexpanded Stent by Rotational Atherectomy

PubMed Central

Vales, Lori; Coppola, John; Kwan, Tak

2013-01-01

The current routine use of intracoronary stents in percutaneous coronary intervention (PCI) has significantly reduced rates of restenosis, compared with balloon angioplasty alone. On the contrary, small post-stenting luminal dimensions due to undilatable, heavily calcified plaques have repeatedly been shown to significantly increase the rates of in-stent restenosis. Rotational atherectomy of lesions is an alternative method to facilitate PCI and prevent underexpansion of stents, when balloon angioplasty fails to successfully dilate a lesion. Stentablation, using rotational atherectomy to expand underexpanded stents deployed in heavily calcified plaques, has also been reported. We report a case via the transradial approach of rotational-atherectomy–facilitated PCI of in-stent restenosis of a severely underexpanded stent due to a heavily calcified plaque. We review the literature and suggest rotational atherectomy may have a role in treating a refractory, severely underexpanded stent caused by a heavily calcified plaque through various proposed mechanisms. PMID:24436587

Regulation of naturally occurring autoantibody secretion by a radiosensitive lymphocyte: initial characterization and ontogeny

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

Moticka, E.J.

1983-10-01

Low level irradiation (400-500 R) of normal mice or of murine spleen cells resulted in the detection of an enhanced number of plaque-forming cells against bromelain-treated autologous red cells (Br MRBC) 1 day later. The mechanism responsible for the increased numbers of plaques is apparently the elimination of a suppressor T cell since the addition of thymocytes or of Lyt 1+2+ splenic cells to cultures of irradiated cells reversed the radiation-induced increase. Studies on the ontogeny of the phenomenon indicate that anti-Br MRBC plaques can be formed by spleen cells taken from mice shortly after birth although adult levels aremore » not reached until after 3 weeks of age. Radiation-induced increases in the number of plaques were not seen until 3 weeks of age, thus, suggesting a temporal developmental sequence of the ability to produce autoantibodies and to regulate such production.« less

Aspartame Intake Relates to Coronary Plaque Burden and Inflammatory Indices in Human Immunodeficiency Virus.

PubMed

Hall, Leangelo N; Sanchez, Laura R; Hubbard, Jane; Lee, Hang; Looby, Sara E; Srinivasa, Suman; Zanni, Markella V; Stanley, Takara L; Lo, Janet; Grinspoon, Steven K; Fitch, Kathleen V

2017-01-01

Dietary sweeteners may contribute to metabolic dysregulation and cardiovascular disease (CVD), but this has not been assessed in human immunodeficiency virus (HIV). One hundred twenty-four HIV-infected and 56 non-HIV-infected participants, without history of known coronary artery disease were included. Dietary intake was assessed using a 4-day food record. Coronary plaque was determined using cardiac computed tomography angiography. Human immunodeficiency virus-infected participants had significantly greater intake of dietary sweeteners, including total sugar ( P = .03) and added sugar ( P = .009); intake of aspartame (artificial sweetener) was greater among aspartame consumers with HIV versus non-HIV consumers ( P = .03). Among HIV-infected participants, aspartame intake was significantly associated with coronary plaque ( P = .002) and noncalcified plaque ( P = .007) segments, as well as markers of inflammation/immune activation (monocyte chemoattractant protein 1 and lipoprotein-associated phospholipase A 2 ), which may contribute to increased atherogenesis. In multivariable regression modeling, aspartame remained an independent predictor of plaque in HIV. In contrast, among non-HIV-infected participants, no sweetener type was shown to relate to plaque characteristics. We demonstrate increased intake of dietary sweeteners and a potential novel association between aspartame intake, plaque burden, and inflammation in HIV. Our data suggest that aspartame may contribute to CVD risk in HIV. Further studies should address potential mechanisms by which aspartame may contribute to increased plaque burden and cardiovascular benefits of dietary strategies targeting aspartame intake in HIV. © The Author 2017. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

Relationship between central and peripheral atherosclerosis and left ventricular dysfunction in a community population.

PubMed

Tsao, Connie W; Gona, Philimon; Salton, Carol; Murabito, Joanne M; Oyama, Noriko; Danias, Peter G; O'Donnell, Christopher J; Manning, Warren J; Yeon, Susan B

2011-08-01

We aimed to determine the relationships between resting left ventricular (LV) wall motion abnormalities (WMAs), aortic plaque, and peripheral artery disease (PAD) in a community cohort. A total of 1726 Framingham Heart Study Offspring Cohort participants (806 males, 65 ± 9 years) underwent cardiovascular magnetic resonance with quantification of aortic plaque volume and assessment of regional left ventricular systolic function. Claudication, lower extremity revascularization, and ankle-brachial index (ABI) were recorded at the most contemporaneous examination visit. WMAs were associated with greater aortic plaque burden, decreased ABI, and claudication in age- and sex-adjusted analyses (all p < 0.001), which were not significant after adjustment for cardiovascular risk factors. In age- and sex-adjusted analyses, both the presence (p < 0.001) and volume of aortic plaque were associated with decreased ABI (p < 0.001). After multivariable adjustment, an ABI ≤ 0.9 or prior revascularization was associated with a threefold odds of aortic plaque (p = 0.0083). Plaque volume significantly increased with decreasing ABI in multivariable-adjusted analyses (p < 0.0001). In this free-living population, associations of WMAs with aortic plaque burden and clinical measures of PAD were attenuated after adjustment for coronary heart disease risk factors. Aortic plaque volume and ABI remained strongly negatively correlated after multivariable adjustment. Our findings suggest that the association between coronary heart disease and non-coronary atherosclerosis is explained by cardiovascular risk factors. Aortic atherosclerosis and PAD remain strongly associated after multivariable adjustment, suggesting shared mechanisms beyond those captured by traditional risk factors.

Antibacterial effect of taurolidine (2%) on established dental plaque biofilm.

PubMed

Arweiler, Nicole Birgit; Auschill, Thorsten Mathias; Sculean, Anton

2012-04-01

Preliminary data have suggested that taurolidine may bear promising disinfectant properties for the therapy of bacterial infections. However, at present, the potential antibacterial effect of taurolidine on the supragingival plaque biofilm is unknown. To evaluate the antibacterial effect of taurolidine on the supragingival plaque biofilm using the vital fluorescence technique and to compare it with the effect of NaCl and chlorhexidine (CHX), 18 subjects had to refrain from all mechanical and chemical hygiene measures for 24 h. A voluminous supragingival plaque sample was taken from the buccal surfaces of the lower molars and wiped on an objective slide. The sample was then divided into three equal parts and mounted with one of the three test or control preparations (a) NaCl, (b) taurolidine 2% and (c) CHX 0.2%. After a reaction time of 2 min, the test solutions were sucked of. Subsequently, the plaque biofilm was stained with fluorescence dye and vitality of the plaque flora was evaluated under the fluorescence microscope (VF%). Plaque samples treated with NaCl showed a mean VF of 82.42 ± 6.04%. Taurolidine affected mean VF with 47.57 ± 16.60% significantly (p < 0.001, paired t test). The positive control CHX showed the lowest mean VF values (34.41 ± 14.79%; p < 0.001 compared to NaCl, p = 0.017 compared to taurolidine). Taurolidine possesses a significant antibacterial effect on the supragingival plaque biofilm which was, however, not as pronounced as that of CHX.

Microbiota-based Signature of Gingivitis Treatments: A Randomized Study.

PubMed

Huang, Shi; Li, Zhen; He, Tao; Bo, Cunpei; Chang, Jinlan; Li, Lin; He, Yanyan; Liu, Jiquan; Charbonneau, Duane; Li, Rui; Xu, Jian

2016-04-20

Plaque-induced gingivitis can be alleviated by various treatment regimens. To probe the impacts of various anti-gingivitis treatments on plaque microflora, here a double blinded, randomized controlled trial of 91 adults with moderate gingivitis was designed with two anti-gingivitis regimens: the brush-alone treatment and the brush-plus-rinse treatment. In the later group, more reduction in both Plaque Index (TMQHI) and Gingival Index (mean MGI) at Day 3, Day 11 and Day 27 was evident, and more dramatic changes were found between baseline and other time points for both supragingival plaque microbiota structure and salivary metabonomic profiles. A comparison of plaque microbiota changes was also performed between these two treatments and a third dataset where 50 subjects received regimen of dental scaling. Only Actinobaculum, TM7 and Leptotrichia were consistently reduced by all the three treatments, whereas the different microbial signatures of the three treatments during gingivitis relieve indicate distinct mechanisms of action. Our study suggests that microbiota based signatures can serve as a valuable approach for understanding and potentially comparing the modes of action for clinical treatments and oral-care products in the future.

Microbiota-based Signature of Gingivitis Treatments: A Randomized Study

PubMed Central

Huang, Shi; Li, Zhen; He, Tao; Bo, Cunpei; Chang, Jinlan; Li, Lin; He, Yanyan; Liu, Jiquan; Charbonneau, Duane; Li, Rui; Xu, Jian

2016-01-01

Plaque-induced gingivitis can be alleviated by various treatment regimens. To probe the impacts of various anti-gingivitis treatments on plaque microflora, here a double blinded, randomized controlled trial of 91 adults with moderate gingivitis was designed with two anti-gingivitis regimens: the brush-alone treatment and the brush-plus-rinse treatment. In the later group, more reduction in both Plaque Index (TMQHI) and Gingival Index (mean MGI) at Day 3, Day 11 and Day 27 was evident, and more dramatic changes were found between baseline and other time points for both supragingival plaque microbiota structure and salivary metabonomic profiles. A comparison of plaque microbiota changes was also performed between these two treatments and a third dataset where 50 subjects received regimen of dental scaling. Only Actinobaculum, TM7 and Leptotrichia were consistently reduced by all the three treatments, whereas the different microbial signatures of the three treatments during gingivitis relieve indicate distinct mechanisms of action. Our study suggests that microbiota based signatures can serve as a valuable approach for understanding and potentially comparing the modes of action for clinical treatments and oral-care products in the future. PMID:27094556

Phylogenetic Analysis Shows That Neolithic Slate Plaques from the Southwestern Iberian Peninsula Are Not Genealogical Recording Systems

PubMed Central

García Rivero, Daniel; O'Brien, Michael J.

2014-01-01

Prehistoric material culture proposed to be symbolic in nature has been the object of considerable archaeological work from diverse theoretical perspectives, yet rarely are methodological tools used to test the interpretations. The lack of testing is often justified by invoking the opinion that the slippery nature of past human symbolism cannot easily be tackled by the scientific method. One such case, from the southwestern Iberian Peninsula, involves engraved stone plaques from megalithic funerary monuments dating ca. 3,500–2,750 B.C. (calibrated age). One widely accepted proposal is that the plaques are ancient mnemonic devices that record genealogies. The analysis reported here demonstrates that this is not the case, even when the most supportive data and techniques are used. Rather, we suspect there was a common ideological background to the use of plaques that overlay the southwestern Iberian Peninsula, with little or no geographic patterning. This would entail a cultural system in which plaque design was based on a fundamental core idea, with a number of mutable and variable elements surrounding it. PMID:24558384

Fluoride-induced enhancement of diffusion in streptococcal model plaque biofilms.

PubMed

Rose, R K; Turner, S J

1998-01-01

It has been demonstrated that fluoride decreases the calcium-binding affinity of Streptococcus mutans and approximately doubles the calcium-binding capacity. To investigate the effect of this mechanism on calcium mobility in plaque, 45Ca flux was measured from a condensed films of S. mutans into tracer-free solution. Bacteria were suspended in pH 7.0 or 5.0 buffer including 0, 5, 10, 15 or 20 mmol/l Ca2+ carrier, with or without 5 mmol/l F- and with 45Ca and 3H-inulin. The appearance of 45Ca and 3H-inulin in carrier-containing but initially tracer-free buffer was measured and extracellular fraction (Ve) and bound calcium were calculated. As the ratio (R) of bound to free Ca2+ approached zero at high [Ca2+], the measured diffusion coefficient (rDe) approached the effective diffusion coefficient (De), such that: rDe = De/(1+R). Fluoride increased the rate of calcium diffusion by a reduction in the binding affinity. This work demonstrates that fluoride significantly increases mobility in plaque; this may increase the rate at which calcium is transported between plaque and an underlying lesion and so promote remineralization. This mechanism could also increase the penetration of bacteriocides and suggests a novel method for biofilm treatment.

Nanomedicine for the molecular diagnosis of cardiovascular pathologies

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

Juenet, Maya; Varna, Mariana; Aid-Launais, Rachida

Predicting acute clinical events caused by atherosclerotic plaque rupture remains a clinical challenge. Anatomic mapping of the vascular tree provided by standard imaging technologies is not always sufficient for a robust diagnosis. Yet biological mechanisms leading to unstable plaques have been identified and corresponding biomarkers have been described. Nanosystems charged with contrast agents and targeted towards these specific biomarkers have been developed for several types of imaging modalities. The first systems that have reached the clinic are ultrasmall superparamagnetic iron oxides for Magnetic Resonance Imaging. Their potential relies on their passive accumulation by predominant physiological mechanisms in rupture-prone plaques. Activemore » targeting strategies are under development to improve their specificity and set up other types of nanoplatforms. Preclinical results show a huge potential of nanomedicine for cardiovascular diagnosis, as long as the safety of these nanosystems in the body is studied in depth. - Highlights: • Ischemic stroke and myocardial infarction are the main causes of death in the world. • Their prevalence is related to late detection of high-risk atherosclerotic plaques. • Biomarkers of atherosclerosis evolution and potential ligands have been identified. • Nanosystems based on these ligands appear promising for early molecular diagnosis. • Preclinical and clinical nanosystems for common imaging modalities are described.« less

Differences in root aeration, iron plaque formation and waterlogging tolerance in six mangroves along a continues tidal gradient.

PubMed

Cheng, Hao; Wang, You-Shao; Fei, Jiao; Jiang, Zhao-Yu; Ye, Zhi-Hong

2015-10-01

Mangrove is a special coastal forest along tropical and subtropical intertidal shores. However, how mangroves adapt to tidal flooding and the mechanisms involved in mangrove zonation are still poorly understood. In this study, a pot trial with different tide treatments was conducted to investigate the differences in root anatomy, porosity, radial oxygen loss, iron plaque formation and waterlogging tolerance among six mangroves along a continuous tidal gradient. The index of waterlogging tolerance illustrated that Sonneratia apetala possessed the highest index, followed by Aeguceras corniculatum/Kandelia, Rhizophora stylosa, Heritiera littorlis and Thespesia populnea. Waterlogging tolerances of the mangroves were found to be positively correlated with their root porosity, radial oxygen loss and iron plaque formation. Waterlogging-sensitive species such as landward semi-mangroves exhibited small root porosity and ROL, while waterlogging-tolerant species such as seaward pioneer and rhizophoraceous mangroves exhibited extensive porosity, ROL and iron plaque formation. Nevertheless, grater root porosity and iron plaque formation were detected in permanent waterlogged plants when compared to drained plants. In conclusion, The present study proposes a structural adaptive strategy to tidal flooding in mangroves, such that the mangroves with higher root porosity, ROL and iron plaque appeared to exhibit higher waterlogging tolerance and adaptability in anaerobic foreshores.

The plaque- and gingivitis-inhibiting capacity of a commercially available essential oil product. A parallel, split-mouth, single blind, randomized, placebo-controlled clinical study.

PubMed

Preus, Hans Ragnar; Koldsland, Odd Carsten; Aass, Anne Merete; Sandvik, Leiv; Hansen, Bjørn Frode

2013-11-01

Studies have reported commercially available essential oils with convincing plaque and gingivitis preventing properties. However, no tests have compared these essential oils, i.e. Listerine(®), against their true vehicle controls. To compare the plaque and gingivitis inhibiting effect of a commercially-available essential oil (Listerine(®) Total Care) to a negative (22% hydro-alcohol solution) and a positive (0.2% chlorhexidine (CHX)) control in an experimental gingivitis model. In three groups of 15 healthy volunteers, experimental gingivitis was induced and monitored over 21 days, simultaneously treated with Listerine(®) Total Care (test), 22% hydro-alcohol solution (negative control) and 0.2% chlorhexidine solution (positive control), respectively. The upper right quadrant of each individual received mouthwash only, whereas the upper left quadrant was subject to both rinses and mechanical oral hygiene. Plaque, gingivitis and side-effects were assessed at day 7, 14 and 21. After 21 days, the chlorhexidine group showed significantly lower average plaque and gingivitis scores than the Listerine(®) and alcohol groups, whereas there was little difference between the two latter. Listerine(®) Total Care had no statistically significant effect on plaque formation as compared to its vehicle control.

Carotid Plaque Morphological Classification Compared With Biomechanical Cap Stress: Implications for a Magnetic Resonance Imaging-Based Assessment.

PubMed

Gijsen, Frank J H; Nieuwstadt, Harm A; Wentzel, Jolanda J; Verhagen, Hence J M; van der Lugt, Aad; van der Steen, Antonius F W

2015-08-01

Two approaches to target plaque vulnerability-a histopathologic classification scheme and a biomechanical analysis-were compared and the implications for noninvasive risk stratification of carotid plaques using magnetic resonance imaging were assessed. Seventy-five histological plaque cross sections were obtained from carotid endarterectomy specimens from 34 patients (>70% stenosis) and subjected to both a Virmani histopathologic classification (thin fibrous cap atheroma with <0.2-mm cap thickness, presumed vulnerable) and a peak cap stress computation (<140 kPa: presumed stable; >300 kPa: presumed vulnerable). To demonstrate the implications for noninvasive plaque assessment, numeric simulations of a typical carotid magnetic resonance imaging protocol were performed (0.62×0.62 mm(2) in-plane acquired voxel size) and used to obtain the magnetic resonance imaging-based peak cap stress. Peak cap stress was generally associated with histological classification. However, only 16 of 25 plaque cross sections could be labeled as high-risk (peak cap stress>300 kPa and classified as a thin fibrous cap atheroma). Twenty-eight of 50 plaque cross sections could be labeled as low-risk (a peak cap stress<140 kPa and not a thin fibrous cap atheroma), leading to a κ=0.39. 31 plaques (41%) had a disagreement between both classifications. Because of the limited magnetic resonance imaging voxel size with regard to cap thickness, a noninvasive identification of only a group of low-risk, thick-cap plaques was reliable. Instead of trying to target only vulnerable plaques, a more reliable noninvasive identification of a select group of stable plaques with a thick cap and low stress might be a more fruitful approach to start reducing surgical interventions on carotid plaques. © 2015 American Heart Association, Inc.

Around Marshall

NASA Image and Video Library

2000-10-26

This plaque, located on the grounds of Marshall Space Flight Center in Huntsville, Alabama,commemorates the designation of the Saturn V Rocket as a National Historic Mechanical Engineering Landmark by the American Society of Mechanical Engineers in 1980.

Gadolinium Enhancement in Intracranial Atherosclerotic Plaque and Ischemic Stroke: A Systematic Review and Meta-Analysis.

PubMed

Gupta, Ajay; Baradaran, Hediyeh; Al-Dasuqi, Khalid; Knight-Greenfield, Ashley; Giambrone, Ashley E; Delgado, Diana; Wright, Drew; Teng, Zhongzhao; Min, James K; Navi, Babak B; Iadecola, Costantino; Kamel, Hooman

2016-08-15

Gadolinium enhancement on high-resolution magnetic resonance imaging (MRI) has been proposed as a marker of inflammation and instability in intracranial atherosclerotic plaque. We performed a systematic review and meta-analysis to summarize the association between intracranial atherosclerotic plaque enhancement and acute ischemic stroke. We searched the medical literature to identify studies of patients undergoing intracranial vessel wall MRI for evaluation of intracranial atherosclerotic plaque. We recorded study data and assessed study quality, with disagreements in data extraction resolved by a third reader. A random-effects odds ratio was used to assess whether, in any given patient, cerebral infarction was more likely in the vascular territory supplied by an artery with MRI-detected plaque enhancement as compared to territory supplied by an artery without enhancement. We calculated between-study heterogeneity using the Cochrane Q test and publication bias using the Begg-Mazumdar test. Eight articles published between 2011 and 2015 met inclusion criteria. These studies provided information about plaque enhancement characteristics from 295 arteries in 330 patients. We found a significant positive relationship between MRI enhancement and cerebral infarction in the same vascular territory, with a random effects odds ratio of 10.8 (95% CI 4.1-28.1, P<0.001). No significant heterogeneity (Q=11.08, P=0.14) or publication bias (P=0.80) was present. Intracranial plaque enhancement on high-resolution vessel wall MRI is strongly associated with ischemic stroke. Evaluation for plaque enhancement on MRI may be a useful test to improve diagnostic yield in patients with ischemic strokes of undetermined etiology. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Long Life Nickel Electrodes for a Nickel-hydrogen Cell: Cycle Life Tests

NASA Technical Reports Server (NTRS)

Lim, H. S.; Verzwyvelt, S. A.

1984-01-01

In order to develop a long life nickel electrode for a Ni/H2 cell, cycle life tests of nickel electrodes were carried out in Hi/H2 boiler plate cells. A 19 test cell matrix was made of various nickel electrode designs including three levels each of plaque mechanical strength, median pore size of the plaque, and active material loading. Test cells were cycled to the end of their life (0.5v) in a 45-minute low earth orbit cycle regime at 80% depth-of-discharge. The results show that the active material loading level affects the cycle life the most with the optimum loading at 1.6 g/cc void. Mechanical strength did not affect the cycle life noticeably in the bend strength range of 400 to 700 psi. The best plaque type appears to be one which is made of INCO nickel powder type 287 and has a median pore size of 13 micron.

Red fluorescence imaging for dental plaque detection and quantification: pilot study

NASA Astrophysics Data System (ADS)

Liu, Zhao; Gomez, Juliana; Khan, Soniya; Peru, Debbie; Ellwood, Roger

2017-09-01

The red fluorescence of dental plaque originating from porphyrins in oral bacteria may allow visualization, detection, and scoring of plaque without disclosing agents. Two studies were conducted. The first included 24 healthy participants who abstained from oral hygiene for 24 h. Dental plaque was collected from tooth surfaces, and a 10% solution was prepared. These were scanned by a molecular spectrometer to identify the optimum excitation and emission wavelengths of plaque for developing a red fluorescence imaging system. Fourteen healthy subjects completed the second study. After a washout period (1 week), participants had a prophylaxis at baseline and abstained from oral hygiene during the study. They were monitored using the fluorescence imaging system at baseline, 24 h, and 48 h. A dentist clinically assessed plaque after disclosing and on red fluorescence images. Three descriptors were extracted from images and a RUSBoost classifier derived computer fluorescence scores through cross-validation. Red fluorescence plaque levels increased during the 48-h accumulation. Plaque progression was identified by dentist assessment and computer analysis, presenting significant differences between visits at tooth and subject levels (p<0.05). Moderate correlations showed between clinical plaque and red fluorescence plaque (r=0.62 dentist, r=0.55 computer). The best agreement was observed when disclosing plaque threshold at level 2, for both dentist evaluation (sensitivity 71.1%, specificity 67.7%, accuracy 70.2%) and computer classification (sensitivity 68.4%, specificity 62.9%, accuracy 67.1%). Given the correlation with clinical diagnosis, red fluorescence imaging shows its potential for providing an objective and promising method for proper oral hygiene assessment.

The association of lesion eccentricity with plaque morphology and components in the superficial femoral artery: a high-spatial-resolution, multi-contrast weighted CMR study.

PubMed

Li, Feiyu; McDermott, Mary McGrae; Li, Debiao; Carroll, Timothy J; Hippe, Daniel S; Kramer, Christopher M; Fan, Zhaoyang; Zhao, Xihai; Hatsukami, Thomas S; Chu, Baocheng; Wang, Jinnan; Yuan, Chun

2010-07-01

Atherosclerotic plaque morphology and components are predictors of subsequent cardiovascular events. However, associations of plaque eccentricity with plaque morphology and plaque composition are unclear. This study investigated associations of plaque eccentricity with plaque components and morphology in the proximal superficial femoral artery using cardiovascular magnetic resonance (CMR). Twenty-eight subjects with an ankle-brachial index less than 1.00 were examined with 1.5 T high-spatial-resolution, multi-contrast weighted CMR. One hundred and eighty diseased locations of the proximal superficial femoral artery (about 40 mm) were analyzed. The eccentric lesion was defined as [(Maximum wall thickness- Minimum wall thickness)/Maximum wall thickness] >or= 0.5. The arterial morphology and plaque components were measured using semi-automatic image analysis software. One hundred and fifteen locations were identified as eccentric lesions and sixty-five as concentric lesions. The eccentric lesions had larger wall but similar lumen areas, larger mean and maximum wall thicknesses, and more calcification and lipid rich necrotic core, compared to concentric lesions. For lesions with the same lumen area, the degree of eccentricity was associated with an increased wall area. Eccentricity (dichotomous as eccentric or concentric) was independently correlated with the prevalence of calcification (odds ratio 3.78, 95% CI 1.47-9.70) after adjustment for atherosclerotic risk factors and wall area. Plaque eccentricity is associated with preserved lumen size and advanced plaque features such as larger plaque burden, more lipid content, and increased calcification in the superficial femoral artery.

Dental plaque removal with a novel battery-powered toothbrush.

PubMed

Biesbrock, Aaron R; Walters, Patricia; Bartizek, Robert D; Ruhlman, Douglas; Donly, Kevin J

2002-04-01

To compare the plaque removal efficacy of a positive control power toothbrush (Oral-B Ultra Plaque Remover) to an experimental power toothbrush (Crest SpinBrush) following a single use. This study was a randomized, controlled, examiner-blind, 2-period crossover design which examined plaque removal with the two toothbrushes following a single use in 38 completed subjects. Plaque was scored before and after brushing using the Turesky Modification of the Quigley-Hein Index. Baseline plaque scores were 1.89 and 1.91 for the experimental toothbrush and control toothbrush treatment groups, respectively. With respect to all surfaces examined, the experimental toothbrush delivered an adjusted (via analysis of covariance) mean difference between baseline and post-brushing plaque scores of 0.46 while the control toothbrush delivered an adjusted mean difference of 0.45. These results were not statistically significant (P=0.645). A 95% one-sided upper confidence limit on the Ultra Plaque Remover minus SpinBrush difference in amount of plaque removed was calculated as 9.4% of the Ultra Plaque Remover adjusted mean. A common criterion for what is known as an "at least as good as" test is that the 95% one-sided confidence limit on the product difference is below 10% of the control product mean. Using this criterion, the SpinBrush is at least as good as the Oral-B Ultra Plaque Remover. With respect to buccal and lingual surfaces, the experimental toothbrush delivered very similar results relative to the control toothbrush. These results were also not statistically significant (P> 0.564).

Automated image-based assay for evaluation of HIV neutralization and cell-to-cell fusion inhibition.

PubMed

Sheik-Khalil, Enas; Bray, Mark-Anthony; Özkaya Şahin, Gülsen; Scarlatti, Gabriella; Jansson, Marianne; Carpenter, Anne E; Fenyö, Eva Maria

2014-08-30

Standardized techniques to detect HIV-neutralizing antibody responses are of great importance in the search for an HIV vaccine. Here, we present a high-throughput, high-content automated plaque reduction (APR) assay based on automated microscopy and image analysis that allows evaluation of neutralization and inhibition of cell-cell fusion within the same assay. Neutralization of virus particles is measured as a reduction in the number of fluorescent plaques, and inhibition of cell-cell fusion as a reduction in plaque area. We found neutralization strength to be a significant factor in the ability of virus to form syncytia. Further, we introduce the inhibitory concentration of plaque area reduction (ICpar) as an additional measure of antiviral activity, i.e. fusion inhibition. We present an automated image based high-throughput, high-content HIV plaque reduction assay. This allows, for the first time, simultaneous evaluation of neutralization and inhibition of cell-cell fusion within the same assay, by quantifying the reduction in number of plaques and mean plaque area, respectively. Inhibition of cell-to-cell fusion requires higher quantities of inhibitory reagent than inhibition of virus neutralization.

Catheter design optimization for practical intravascular photoacoustic imaging (IVPA) of vulnerable plaques

NASA Astrophysics Data System (ADS)

Iskander-Rizk, Sophinese; Wu, Min; Springeling, Geert; Mastik, Frits; Beurskens, Robert H. S. H.; van der Steen, Antonius F. W.; van Soest, Gijs

2018-02-01

Intravascular photoacoustic/ultrasound imaging (IVPA/US) can image the structure and composition of atherosclerotic lesions identifying lipid-rich plaques ex vivo and in vivo. In the literature, multiple IVPA/US catheter designs were presented and validated both in ex-vivo models and preclinical in-vivo situations. Since the catheter is a critical component of the imaging system, we discuss here a catheter design oriented to imaging plaque in a realistic and translatable setting. We present a catheter optimized for light delivery, manageable flush parameters and robustness with reduced mechanical damage risks at the laser/catheter joint interface. We also show capability of imaging within sheath and in water medium.

Microbial carriage state of peripheral blood dendritic cells (DCs) in chronic periodontitis influences DC differentiation, atherogenic potential.

PubMed

Carrion, Julio; Scisci, Elizabeth; Miles, Brodie; Sabino, Gregory J; Zeituni, Amir E; Gu, Ying; Bear, Adam; Genco, Caroline A; Brown, David L; Cutler, Christopher W

2012-09-15

The low-grade oral infection chronic periodontitis (CP) has been implicated in coronary artery disease risk, but the mechanisms are unclear. In this study, a pathophysiological role for blood dendritic cells (DCs) in systemic dissemination of oral mucosal pathogens to atherosclerotic plaques was investigated in humans. The frequency and microbiome of CD19(-)BDCA-1(+)DC-SIGN(+) blood myeloid DCs (mDCs) were analyzed in CP subjects with or without existing acute coronary syndrome and in healthy controls. FACS analysis revealed a significant increase in blood mDCs in the following order: healthy controls < CP < acute coronary syndrome/CP. Analysis of the blood mDC microbiome by 16S rDNA sequencing showed Porphyromonas gingivalis and other species, including (cultivable) Burkholderia cepacia. The mDC carriage rate with P. gingivalis correlated with oral carriage rate and with serologic exposure to P. gingivalis in CP subjects. Intervention (local debridement) to elicit a bacteremia increased the mDC carriage rate and frequency in vivo. In vitro studies established that P. gingivalis enhanced by 28% the differentiation of monocytes into immature mDCs; moreover, mDCs secreted high levels of matrix metalloproteinase-9 and upregulated C1q, heat shock protein 60, heat shock protein 70, CCR2, and CXCL16 transcripts in response to P. gingivalis in a fimbriae-dependent manner. Moreover, the survival of the anaerobe P. gingivalis under aerobic conditions was enhanced when within mDCs. Immunofluorescence analysis of oral mucosa and atherosclerotic plaques demonstrate infiltration with mDCs, colocalized with P. gingivalis. Our results suggest a role for blood mDCs in harboring and disseminating pathogens from oral mucosa to atherosclerosis plaques, which may provide key signals for mDC differentiation and atherogenic conversion.

Lapaquistat acetate, a squalene synthase inhibitor, changes macrophage/lipid-rich coronary plaques of hypercholesterolaemic rabbits into fibrous lesions.

PubMed

Shiomi, M; Yamada, S; Amano, Y; Nishimoto, T; Ito, T

2008-07-01

Inhibition of squalene synthesis could transform unstable, macrophage/lipid-rich coronary plaques into stable, fibromuscular plaques. We have here treated WHHLMI rabbits, a model for coronary atherosclerosis and myocardial infarction, with a novel squalene synthase inhibitor, lapaquistat acetate (TAK-475). Young male WHHLMI rabbits were fed a diet supplemented with lapaquistat acetate (100 or 200 mg per kg body weight per day) for 32 weeks. Serum lipid levels were monitored every 4 weeks. After the treatment, lipoprotein lipid and coenzyme Q10 levels were assayed, and coronary atherosclerosis and xanthomas were examined histopathologically or immunohistochemically. From histopathological and immunohistochemical sections, the composition of the plaque was analysed quantitatively with computer-assisted image analysis. Xanthoma was evaluated grossly. Lapaquistat acetate decreased plasma cholesterol and triglyceride levels, by lowering lipoproteins containing apoB100. Development of atherosclerosis and xanthomatosis was suppressed. Accumulation of oxidized lipoproteins, macrophages and extracellular lipid was decreased in coronary plaques of treated animals. Treatment with lapaquistat acetate increased collagen concentration and transformed coronary plaques into fibromuscular plaques. Lapaquistat acetate also suppressed the expression of matrix metalloproteinase-1 and plasminogen activator inhibitor-1 in the plaque and increased peripheral coenzyme Q10 levels. Increased coenzyme Q10 levels and decreased very low-density lipoprotein cholesterol levels were correlated with improvement of coronary plaque composition. Inhibition of squalene synthase by lapaquistat acetate delayed progression of coronary atherosclerosis and changed coronary atheromatous plaques from unstable, macrophage/lipid accumulation-rich, lesions to stable fibromuscular lesions.

64Cu-DOTATATE PET/MRI for Detection of Activated Macrophages in Carotid Atherosclerotic Plaques: Studies in Patients Undergoing Endarterectomy.

PubMed

Pedersen, Sune Folke; Sandholt, Benjamin Vikjær; Keller, Sune Høgild; Hansen, Adam Espe; Clemmensen, Andreas Ettrup; Sillesen, Henrik; Højgaard, Liselotte; Ripa, Rasmus Sejersten; Kjær, Andreas

2015-07-01

A feature of vulnerable atherosclerotic plaques of the carotid artery is high activity and abundance of lesion macrophages. There is consensus that this is of importance for plaque vulnerability, which may lead to clinical events, such as stroke and transient ischemic attack. We used positron emission tomography (PET) and the novel PET ligand [(64)Cu] [1,4,7,10-tetraazacyclododecane-N,N',N″,N‴-tetraacetic acid]-d-Phe1,Tyr3-octreotate ((64)Cu-DOTATATE) to specifically target macrophages via the somatostatin receptor subtype-2 in vivo. Ten patients underwent simultaneous PET/MRI to measure (64)Cu-DOTATATE uptake in carotid artery plaques before carotid endarterectomy. (64)Cu-DOTATATE uptake was significantly higher in symptomatic plaque versus the contralateral carotid artery (P<0.001). Subsequently, a total of 62 plaque segments were assessed for gene expression of selected markers of plaque vulnerability using real-time quantitative polymerase chain reaction. These results were compared with in vivo (64)Cu-DOTATATE uptake calculated as the mean standardized uptake value. Univariate analysis of real-time quantitative polymerase chain reaction and PET showed that cluster of differentiation 163 (CD163) and CD68 gene expression correlated significantly but weakly with mean standardized uptake value in scans performed 85 minutes post injection (P<0.001 and P=0.015, respectively). Subsequent multivariate analysis showed that CD163 correlated independently with (64)Cu-DOTATATE uptake (P=0.031) whereas CD68 did not contribute significantly to the final model. The novel PET tracer (64)Cu-DOTATATE accumulates in atherosclerotic plaques of the carotid artery. CD163 gene expression correlated independently with (64)Cu-DOTATATE uptake measured by real-time quantitative polymerase chain reaction in the final multivariate model, indicating that (64)Cu-DOTATATE PET is detecting alternatively activated macrophages. This association could potentially improve noninvasive identification and characterization of vulnerable plaques. © 2015 The Authors.

Computer-implemented system and method for automated and highly accurate plaque analysis, reporting, and visualization

NASA Technical Reports Server (NTRS)

Kemp, James Herbert (Inventor); Talukder, Ashit (Inventor); Lambert, James (Inventor); Lam, Raymond (Inventor)

2008-01-01

A computer-implemented system and method of intra-oral analysis for measuring plaque removal is disclosed. The system includes hardware for real-time image acquisition and software to store the acquired images on a patient-by-patient basis. The system implements algorithms to segment teeth of interest from surrounding gum, and uses a real-time image-based morphing procedure to automatically overlay a grid onto each segmented tooth. Pattern recognition methods are used to classify plaque from surrounding gum and enamel, while ignoring glare effects due to the reflection of camera light and ambient light from enamel regions. The system integrates these components into a single software suite with an easy-to-use graphical user interface (GUI) that allows users to do an end-to-end run of a patient record, including tooth segmentation of all teeth, grid morphing of each segmented tooth, and plaque classification of each tooth image.

In vitro determination of the mechanical and chemical properties of a fibre orthodontic retainer.

PubMed

Silvestrini-Biavati, Armando; Angiero, Francesca; Gibelli, Francesca; Signore, Antonio; Benedicenti, Stefano

2012-12-01

The aim of this study was to analyse, in vitro, the chemical and mechanical properties of a new fibre retainer, Everstick, comparing its characteristics with the requirements for an orthodontic retainer. Chemical analysis was used to examine seven fibre bundles exposed to a photocuring lamp and then to different acids and resistance to corrosion by artificial saliva fortified with plaque acids. The mechanical properties examined were tensile strength and resistance to flexural force. Ten fibre samples were tested for each mechanical analysis and the mean value and standard deviation were calculated. Wilcoxon signed rank test was used to evaluate change in weight after treatment in each group. To determine changes over time between the groups for each acid considered separately, both repeated measures analysis of variance (ANOVA) on original data and on rank transformed data were used. If the results were different, ANOVA on rank-transformed data was considered. Acetic acid was found to be the most corrosive and caused the most substance loss: both pure and at the salivary pH value. Hydrofluoric acid was the most damaging. For all acids analysed in both groups (lactic, formic, acetic, propionic), changes after treatment were statistically different between two groups (P < 0.001 for lactic, acetic, propionic; P = 0.004 for formic acid).The mean Young's modulus value was 68 510 MPa. Deformation before the fibre separated into its constituent elements (glass fibre and composite) was 3.9 per cent, stress to rupture was 1546 MPa, and resistance to bending was 534 MPa. The deflection produced over a length of 12 mm was 1.4 mm. The fibre bundle was attacked by acids potentially present in the oral cavity; the degree of aggressiveness depending on the acid concentration. To preserve fibre bundles long term, careful plaque control is necessary, especially in the interproximal spaces, to avoid acid formation. The tested product was found to be sufficiently strong to oppose flexural and occlusal forces.

Preliminary antiplaque efficacy of aloe vera mouthwash on 4 day plaque re-growth model: randomized control trial.

PubMed

Gupta, Rajendra Kumar; Gupta, Devanand; Bhaskar, Dara John; Yadav, Ankit; Obaid, Khursheed; Mishra, Sumit

2014-04-01

Due to increasing resistance to antibiotics and rising incidence of oral diseases, there is a need for alternative treatment modalities to combat oral diseases. The aim of the present study was to access the effect of Aloe vera mouthwash on the dental plaque in the experimental period of 4 days and to compare it with the bench mark control chlorhexidine and placebo (saline water). A total of 300 systemically healthy subjects were randomly allocated into 3 groups: Aloe vera mouthwash group (n=100), control group (=100)-chlorhexidene group and saline water-Placebo (n=100). To begin with, Gingival index (GI) and plaque index (PI) were recorded. Then, baseline plaque scores were brought to zero by professionally cleaning the teeth with scaling and polishing. After randomization of the participants into three groups they were refrained from regular mechanical oral hygiene measures. Subjects were asked to swish with respective mouthwash (Aloe vera mouthwash, 0.2%chlorhexidine gluconate mouthwash, or normal saline) as per therapeutic dose for 4 days. The results showed that Aloe vera mouthrinse is equally effective in reducing plaque as Chlorhexidine compared to placebo over a period of 4 days. There was a significant reduction on plaque in Aloe vera and chlorhexidine groups and no statistically significant difference was observed among them (p>0.05). Aloe vera mouthwash showed no side effects. The results of the present study indicated that Aloe vera may prove an effective mouthwash due to its ability in reducing dental plaque.

Material properties of components in human carotid atherosclerotic plaques: a uniaxial extension study.

PubMed

Teng, Zhongzhao; Zhang, Yongxue; Huang, Yuan; Feng, Jiaxuan; Yuan, Jianmin; Lu, Qingsheng; Sutcliffe, Michael P F; Brown, Adam J; Jing, Zaiping; Gillard, Jonathan H

2014-12-01

Computational modelling to calculate the mechanical loading within atherosclerotic plaques has been shown to be complementary to defining anatomical plaque features in determining plaque vulnerability. However, its application has been partially impeded by the lack of comprehensive knowledge about the mechanical properties of various tissues within the plaque. Twenty-one human carotid plaques were collected from endarterectomy. The plaque was cut into rings, and different type of atherosclerotic tissues, including media, fibrous cap (FC), lipid and intraplaque haemorrhage/thrombus (IPH/T) was dissected for uniaxial extension testing. In total, 65 media strips from 17 samples, 59 FC strips from 14 samples, 38 lipid strips from 11 samples, and 21 IPH/T strips from 11 samples were tested successfully. A modified Mooney-Rivlin strain energy density function was used to characterize the stretch-stress relationship. The stiffnesses of media and FC are comparable, as are lipid and IPH/T. However, both media and FC are stiffer than either lipid or IPH/T. The median values of incremental Young's modulus of media, FC, lipid and IPH/T at λ=1 are 290.1, 244.5, 104.4, 52.9, respectively; they increase to 1019.5, 817.4, 220.7 and 176.9 at λ=1.1; and 4302.7, 3335.0, 533.4 and 268.8 at λ=1.15 (unit, kPa; λ, stretch ratio). The material constants of each tissue type are suggested to be: media, c1=0.138kPa, D1=3.833kPa and D2=18.803; FC, c1=0.186kPa, D1=5.769kPa and D2=18.219; lipid, c1=0.046kPa, D1=4.885kPa and D2=5.426; and IPH/T, c1=0.212kPa, D1=4.260kPa and D2=5.312. It is concluded that all soft atherosclerotic tissues are non-linear, and both media and FC are stiffer than either lipid or IPH/T. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Fluoride bioavailability in saliva and plaque

PubMed Central

2012-01-01

Background Different fluoride formulations may have different effects on caries prevention. It was the aim of this clinical study to assess the fluoride content, provided by NaF compared to amine fluoride, in saliva and plaque. Methods Eight trained volunteers brushed their teeth in the morning for 3 minutes with either NaF or amine fluoride, and saliva and 3-day-plaque-regrowth was collected at 5 time intervals during 6 hours after tooth brushing. The amount of collected saliva and plaque was measured, and the fluoride content was analysed using a fluoride sensitive electrode. All subjects repeated all study cycles 5 times, and 3 cycles per subject underwent statistical analysis using the Wilcoxon-Mann-Whitney test. Results Immediately after brushing the fluoride concentration in saliva increased rapidly and dropped to the baseline level after 360 minutes. No difference was found between NaF and amine fluoride. All plaque fluoride levels were elevated after 30 minutes until 120 minutes after tooth brushing, and decreasing after 360 minutes to baseline. According to the highly individual profile of fluoride in saliva and plaque, both levels of bioavailability correlated for the first 30 minutes, and the fluoride content of saliva and plaque was back to baseline after 6 hours. Conclusions Fluoride levels in saliva and plaque are interindividually highly variable. However, no significant difference in bioavailability between NaF and amine fluoride, in saliva, or in plaque was found. PMID:22230722

A Cross-Sectional Survey of Bacterial Species in Plaque from Client Owned Dogs with Healthy Gingiva, Gingivitis or Mild Periodontitis

PubMed Central

Davis, Ian J.; Wallis, Corrin; Deusch, Oliver; Colyer, Alison; Milella, Lisa; Loman, Nick; Harris, Stephen

2013-01-01

Periodontal disease is the most widespread oral disease in dogs which if left untreated results in significant pain to the pet and loss of dentition. The objective of this study was to identify bacterial species in canine plaque that are significantly associated with health, gingivitis and mild periodontitis (<25% attachment loss). In this survey subgingival plaque samples were collected from 223 dogs with healthy gingiva, gingivitis and mild periodontitis with 72 to 77 samples per health status. DNA was extracted from the plaque samples and subjected to PCR amplification of the V1-V3 region of the 16S rDNA. Pyrosequencing of the PCR amplicons identified a total of 274 operational taxonomic units after bioinformatic and statistical analysis. Porphyromonas was the most abundant genus in all disease stages, particularly in health along with Moraxella and Bergeyella. Peptostreptococcus, Actinomyces, and Peptostreptococcaceae were the most abundant genera in mild periodontitis. Logistic regression analysis identified species from each of these genera that were significantly associated with health, gingivitis or mild periodontitis. Principal component analysis showed distinct community profiles in health and disease. The species identified show some similarities with health and periodontal disease in humans but also major differences. In contrast to human, healthy canine plaque was found to be dominated by Gram negative bacterial species whereas Gram positive anaerobic species predominate in disease. The scale of this study surpasses previously published research and enhances our understanding of the bacterial species present in canine subgingival plaque and their associations with health and early periodontal disease. PMID:24349448

Comparison between MDCT and Grayscale IVUS in a Quantitative Analysis of Coronary Lumen in Segments with or without Atherosclerotic Plaques

PubMed Central

Falcão, João L. A. A.; Falcão, Breno A. A.; Gurudevan, Swaminatha V.; Campos, Carlos M.; Silva, Expedito R.; Kalil-Filho, Roberto; Rochitte, Carlos E.; Shiozaki, Afonso A.; Coelho-Filho, Otavio R.; Lemos, Pedro A.

2015-01-01

Background The diagnostic accuracy of 64-slice MDCT in comparison with IVUS has been poorly described and is mainly restricted to reports analyzing segments with documented atherosclerotic plaques. Objectives We compared 64-slice multidetector computed tomography (MDCT) with gray scale intravascular ultrasound (IVUS) for the evaluation of coronary lumen dimensions in the context of a comprehensive analysis, including segments with absent or mild disease. Methods The 64-slice MDCT was performed within 72 h before the IVUS imaging, which was obtained for at least one coronary, regardless of the presence of luminal stenosis at angiography. A total of 21 patients were included, with 70 imaged vessels (total length 114.6 ± 38.3 mm per patient). A coronary plaque was diagnosed in segments with plaque burden > 40%. Results At patient, vessel, and segment levels, average lumen area, minimal lumen area, and minimal lumen diameter were highly correlated between IVUS and 64-slice MDCT (p < 0.01). However, 64-slice MDCT tended to underestimate the lumen size with a relatively wide dispersion of the differences. The comparison between 64-slice MDCT and IVUS lumen measurements was not substantially affected by the presence or absence of an underlying plaque. In addition, 64-slice MDCT showed good global accuracy for the detection of IVUS parameters associated with flow-limiting lesions. Conclusions In a comprehensive, multi-territory, and whole-artery analysis, the assessment of coronary lumen by 64-slice MDCT compared with coronary IVUS showed a good overall diagnostic ability, regardless of the presence or absence of underlying atherosclerotic plaques. PMID:25993595

A cross-sectional survey of bacterial species in plaque from client owned dogs with healthy gingiva, gingivitis or mild periodontitis.

PubMed

Davis, Ian J; Wallis, Corrin; Deusch, Oliver; Colyer, Alison; Milella, Lisa; Loman, Nick; Harris, Stephen

2013-01-01

Periodontal disease is the most widespread oral disease in dogs which if left untreated results in significant pain to the pet and loss of dentition. The objective of this study was to identify bacterial species in canine plaque that are significantly associated with health, gingivitis and mild periodontitis (<25% attachment loss). In this survey subgingival plaque samples were collected from 223 dogs with healthy gingiva, gingivitis and mild periodontitis with 72 to 77 samples per health status. DNA was extracted from the plaque samples and subjected to PCR amplification of the V1-V3 region of the 16S rDNA. Pyrosequencing of the PCR amplicons identified a total of 274 operational taxonomic units after bioinformatic and statistical analysis. Porphyromonas was the most abundant genus in all disease stages, particularly in health along with Moraxella and Bergeyella. Peptostreptococcus, Actinomyces, and Peptostreptococcaceae were the most abundant genera in mild periodontitis. Logistic regression analysis identified species from each of these genera that were significantly associated with health, gingivitis or mild periodontitis. Principal component analysis showed distinct community profiles in health and disease. The species identified show some similarities with health and periodontal disease in humans but also major differences. In contrast to human, healthy canine plaque was found to be dominated by Gram negative bacterial species whereas Gram positive anaerobic species predominate in disease. The scale of this study surpasses previously published research and enhances our understanding of the bacterial species present in canine subgingival plaque and their associations with health and early periodontal disease.

Mechanisms of inhibition by fluoride of urease activities of cell suspensions and biofilms of Staphylococcus epidermidis, Streptococcus salivarius, Actinomyces naeslundii and of dental plaque.

PubMed

Barboza-Silva, E; Castro, A C D; Marquis, R E

2005-12-01

Fluoride is known to be a potent inhibitor of bacterial ureases and can also act in the form of hydrofluoric acid as a transmembrane proton conductor to acidify the cytoplasm of intact cells with possible indirect, acid inhibition of urease. Our research objectives were to assess the inhibitory potencies of fluoride for three urease-positive bacteria commonly found in the mouth and to determine the relative importance of direct and indirect inhibition of ureases for overall inhibition of intact cells or biofilms. The experimental design involved intact bacteria in suspensions, mono-organism biofilms, cell extracts, and dental plaque. Standard enzymatic assays for ammonia production from urea were used. We found that ureolysis by cells in suspensions or mono-organism biofilms of Staphylococcus epidermidis, Streptococcus salivarius or Actinomyces naeslundii was inhibited by fluoride at plaque levels of 0.1-0.5 mm in a pH-dependent manner. The results of experiments with the organic weak acids indomethacin and capric acid, which do not directly inhibit urease enzyme, indicated that weak-acid effects leading to cytoplasmic acidification are also involved in fluoride inhibition. However, direct fluoride inhibition of urease appeared to be the major mechanism for reduction in ureolytic activity in acid environments. Results of experiments with freshly harvested supragingival dental plaque indicated responses to fluoride similar to those of S. salivarius with pH-dependent fluoride inhibition and both direct and indirect inhibition of urease. Fluoride can act to diminish alkali production from urea by oral bacteria through direct and indirect mechanisms.

[Preferred sites of accumulation of microbial plaque as shown by the color of the exterior surface of complete dentures].

PubMed

Merdes, L; Soueidan, A; Le Bars, P; Tabbi-Aneni, N

2009-03-01

The observation of the denture plaque for complete dentures caused many clinical works and researches, since 30 years. Most of the studies were interested, by the prosthetic under-surface. New data show that the polished (exterior) surface on the denture palate is colonized more than hard palate. The aim of our study is to locate the favorite zones of the accumulation of the denture plaque on the level of the suction polished faces of the acrylic resin. We proceeded by immersion during 24 hours of 62 used full dentures belongs to 33 patients, with mucous membranes of various clinical aspects in a plaque disclosing solution of erythrosine type. The suction faces were divided into several zones of marking. We record 100% of coloring of the interdental zones on the maxillary and mandibular prosthesis. On maxillary prosthesis: 100% of the former and posterior vestibular zones are colored. The bottom of the palate is colored to 67.74%, a rate equivalent to the zones of fractures. On mandibular prosthesis: retromolar and sublingual zones, are colored to 96.77%. The former hall is colored with a rate of 90.32%. The posterior vestibular zone seems the least colored with a rate of 80.64%. The former area of the hall carved in an aesthetic objective is generally colored as well on the maxillary and mandibular prosthesis. We point out that this zone should not be much carved on the level of the area simulating the attached gum. Patients should be always incited to practice a mechanical hygiene, which takes part largely in the evacuation of the denture plaque on prosthetic surfaces. This revealing plaque use should integrate a clinical attitude of good practice, to motivate a patient with prosthetic hygiene or to detect zones of cracks objectifying a mechanical weakness of a prosthesis to be taken again, as well as the checking of the quality of repair joint during a routine control.

Can insoluble polysaccharide concentration in dental plaque, sugar exposure and cariogenic microorganisms predict early childhood caries? A follow-up study.

PubMed

Parisotto, T M; Stipp, R; Rodrigues, L K A; Mattos-Graner, R O; Costa, L S; Nobre-Dos-Santos, M

2015-08-01

Insoluble polysaccharide (IP) has been associated with caries prevalence in young children. However, the power of IP to predict ECC needs to be demonstrated. To assess the relationships between early childhood caries (ECC) and extracellular insoluble polysaccharides (IP) in dental plaque, sugar exposure and cariogenic microorganisms. Visible plaque on maxillary incisors was recorded, followed by caries diagnosis in 65 preschoolers (3-4 years) at baseline and after 1 year. Plaque was collected for mutans streptococci (MS), total microorganism (TM) and lactobacilli (LB) enumerations in selective media, as well as for IP analysis, which was later assessed by colorimetry. Sugar/sucrose exposure was assessed by a diet chart. Positive correlations were found among the prevalence of caries and MS, TM, LB, solid sucrose and visible dental plaque. Additionally, children with IP concentrations in dental plaque higher than 2.36 μg/mg (odds ratio-OR=6.8), with visible plaque on maxillary incisors (OR=4.3), harbouring LB (OR=13) and exposed to solid sugar more than twice/day (OR=5) showed higher risk of developing caries (p<0.05). Extracellular insoluble polysaccharides, solid sugar/sucrose, visible dental plaque and cariogenic microorganisms could predict caries development, partially explaining the ECC pattern. Copyright © 2015 Elsevier Ltd. All rights reserved.

Comparative efficacy of two battery-powered toothbrushes on dental plaque removal.

PubMed

Ruhlman, C Douglas; Bartizek, Robert D; Biesbrock, Aaron R

2002-01-01

A number of clinical studies have consistently demonstrated that power toothbrushes deliver superior plaque removal compared to manual toothbrushes. Recently, a new power toothbrush (Crest SpinBrush) has been marketed with a design that fundamentally differs from other marketed power toothbrushes. Other power toothbrushes feature a small, round head designed to oscillate for enhanced cleaning between the teeth and below the gumline. The new power toothbrush incorporates a similar round oscillating head in conjunction with fixed bristles, which allows the user to brush with optimal manual brushing technique. The objective of this randomized, examiner-blind, parallel design study was to compare the plaque removal efficacy of a positive control power toothbrush (Colgate Actibrush) to an experimental toothbrush (Crest SpinBrush) following a single use among 59 subjects. Baseline plaque scores were 1.64 and 1.40 for the experimental toothbrush and control toothbrush treatment groups, respectively. With regard to all surfaces examined, the experimental toothbrush delivered an adjusted (via analysis of covariance) mean difference between baseline and post-brushing plaque scores of 0.47, while the control toothbrush delivered an adjusted mean difference of 0.33. On average, the difference between toothbrushes was statistically significant (p = 0.013). Because the covariate slope for the experimental group was statistically significantly greater (p = 0.001) than the slope for the control group, a separate slope model was used. Further analysis demonstrated that the experimental group had statistically significantly greater plaque removal than the control group for baseline plaque scores above 1.43. With respect to buccal surfaces, using a separate slope analysis of covariance, the experimental toothbrush delivered an adjusted mean difference between baseline and post-brushing plaque scores of 0.61, while the control toothbrush delivered an adjusted mean difference of 0.39. This difference between toothbrushes was also statistically significant (p = 0.002). On average, the results on lingual surfaces demonstrated similar directional scores favoring the experimental toothbrush; however these results did not achieve statistical significance. In conclusion, the experimental Crest SpinBrush, with its novel fixed and oscillating bristle design, was found to be more effective than the positive control Colgate Actibrush, which is designed with a small round oscillating cluster of bristles.

Association between Randall's Plaque and Calcifying Nanoparticles

NASA Technical Reports Server (NTRS)

Ciftcioglu, Neva; Vejdani, Kaveh; Lee, Olivia; Mathew, Grace; Aho, Katja M.; Kajander, Olavi; McKay, David S.; Jones, Jeff A.; Hayat, Matthew; Stoller, Marshall L.

2007-01-01

Randall's plaques, first described by Alexander Randall in the 1930s, are small subepithelial calcifications in the renal papillae (RP) that also extend deeply into the renal medulla. Despite the strong correlation between the presence of these plaques and the formation of renal stones, the precise origin and pathogenesis of Randall s plaque formation remain elusive. The discovery of calcifying nanoparticles (CNP) and their detection in many calcifying processes of human tissues has raised hypotheses about their possible involvement in renal stone formation. We collected RP and blood samples from 17 human patients who had undergone laparoscopic nephrectomy due to neoplasia. Homogenized RP tissues and serum samples were cultured for CNP. Scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS) analysis were performed on fixed RP samples. Immunohistochemical staining (IHS) was applied on the tissue samples using CNP-specific monoclonal antibody (mAb). Randall s plaques were visible on gross inspection in 11 out of 17 collected samples. Cultures of all serum samples and 13 tissue homogenates had CNP growth within 4 weeks. SEM revealed spherical apatite formations in 14 samples, with calcium and phosphate peaks detected by EDS analysis. IHS was positive in 9 out of 17 samples. A strong link was found between the presence of Randall s plaques and the detection of CNP, also referred to as nanobacteria. These results suggest new insights into the etiology of Randall's plaque formation, and will help us understand the pathogenesis of stone formation. Further studies on this topic may lead us to new approaches on early diagnosis and novel medical therapies of kidney stone formation.

16S rDNA-based metagenomic analysis of dental plaque and lung bacteria in patients with severe acute exacerbations of chronic obstructive pulmonary disease.

PubMed

Tan, L; Wang, H; Li, C; Pan, Y

2014-12-01

Acute exacerbations of chronic obstructive pulmonary disease (AE-COPD) are leading causes of mortality in hospital intensive care units. We sought to determine whether dental plaque biofilms might harbor pathogenic bacteria that can eventually cause lung infections in patients with severe AE-COPD. Paired samples of subgingival plaque biofilm and tracheal aspirate were collected from 53 patients with severe AE-COPD. Total bacterial DNA was extracted from each sample individually for polymerase chain reaction amplification and/or generation of bacterial 16S rDNA sequences and cDNA libraries. We used a metagenomic approach, based on bacterial 16S rDNA sequences, to compare the distribution of species present in dental plaque and lung. Analysis of 1060 sequences (20 clones per patient) revealed a wide range of aerobic, anaerobic, pathogenic, opportunistic, novel and uncultivable bacterial species. Species indistinguishable between the paired subgingival plaque and tracheal aspirate samples (97-100% similarity in 16S rDNA sequence) were dental plaque pathogens (Aggregatibacter actinomycetemcomitans, Capnocytophaga sputigena, Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola) and lung pathogens (Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa and Streptococcus pneumoniae). Real-time polymerase chain reaction of 16S rDNA indicated lower levels of Pseudomonas aeruginosa and Porphyromonas gingivalis colonizing the dental plaques compared with the paired tracheal aspirate samples. These results support the hypothesis that dental bacteria may contribute to the pathology of severe AE-COPD. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Symptomatic and asymptomatic carotid artery plaque

PubMed Central

Mughal, Majid M; Khan, Mohsin K; DeMarco, J Kevin; Majid, Arshad; Shamoun, Fadi; Abela, George S

2011-01-01

Carotid atherosclerotic plaques represent both stable and unstable atheromatous lesions. Atherosclerotic plaques that are prone to rupture owing to their intrinsic composition such as a large lipid core, thin fibrous cap and intraplaque hemorrhage are associated with subsequent thromboembolic ischemic events. At least 15–20% of all ischemic strokes are attributable to carotid artery atherosclerosis. Characterization of plaques may enhance the understanding of natural history and ultimately the treatment of atherosclerotic disease. MRI of carotid plaque and embolic signals during transcranial Doppler have identified features beyond luminal stenosis that are predictive of future transient ischemic attacks and stroke. The value of specific therapies to prevent stroke in symptomatic and asymptomatic patients with severe carotid artery stenosis are the subject of current research and analysis of recently published clinical trials that are discussed in this article. PMID:21985544

Vascular mechanics of the coronary artery

NASA Technical Reports Server (NTRS)

Veress, A. I.; Vince, D. G.; Anderson, P. M.; Cornhill, J. F.; Herderick, E. E.; Klingensmith, J. D.; Kuban, B. D.; Greenberg, N. L.; Thomas, J. D.

2000-01-01

This paper describes our research into the vascular mechanics of the coronary artery and plaque. The three sections describe the determination of arterial mechanical properties using intravascular ultrasound (IVUS), a constitutive relation for the arterial wall, and finite element method (FEM) models of the arterial wall and atheroma. METHODS: Inflation testing of porcine left anterior descending coronary arteries was conducted. The changes in the vessel geometry were monitored using IVUS, and intracoronary pressure was recorded using a pressure transducer. The creep and quasistatic stress/strain responses were determined. A Standard Linear Solid (SLS) was modified to reproduce the non-linear elastic behavior of the arterial wall. This Standard Non-linear Solid (SNS) was implemented into an axisymetric thick-walled cylinder numerical model. Finite element analysis models were created for five age groups and four levels of stenosis using the Pathobiological Determinants of Atherosclerosis Youth (PDAY) database. RESULTS: The arteries exhibited non-linear elastic behavior. The total tissue creep strain was epsilon creep = 0.082 +/- 0.018 mm/mm. The numerical model could reproduce both the non-linearity of the porcine data and time dependent behavior of the arterial wall found in the literature with a correlation coefficient of 0.985. Increasing age had a strong positive correlation with the shoulder stress level, (r = 0.95). The 30% stenosis had the highest shoulder stress due to the combination of a fully formed lipid pool and a thin cap. CONCLUSIONS: Studying the solid mechanics of the arterial wall and the atheroma provide important insights into the mechanisms involved in plaque rupture.

Plaque removal efficacy of a battery-operated toothbrush compared to a manual toothbrush.

PubMed

Ruhlman, C D; Bartizek, R D; Biesbrock, A R

2001-08-01

Recently, a new power toothbrush has been marketed with a design that fundamentally differs from other marketed power toothbrushes, in that it incorporates a round oscillating head, in conjunction with fixed bristles. The objective of this study was to compare the plaque removal efficacy of a control manual toothbrush (Colgate Navigator) to this experimental power toothbrush (Crest SpinBrush) following a single use. This study was a randomized, controlled, examiner-blind, 4-period crossover design which examined plaque removal with the two toothbrushes following a single use in 40 completed subjects. Plaque was scored before and after brushing using the Turesky Modification of the Quigley-Hein Index. Baseline plaque scores were 1.77 for both the experimental toothbrush and control toothbrush treatment groups. With respect to all surfaces examined, the experimental toothbrush delivered an adjusted (via analysis of covariance) mean difference between baseline and post-brushing plaque scores of 0.48 while the control toothbrush delivered an adjusted mean difference of 0.35. The experimental toothbrush removed, on average, 37.6% more plaque than the control toothbrush. These results were statistically significant (P< 0.001). With respect to buccal surfaces, the experimental toothbrush delivered an adjusted mean difference between baseline and post-brushing plaque scores of 0.54 while the control toothbrush delivered an adjusted mean difference of 0.42. This represents 27.8% more plaque removal with the experimental toothbrush compared to the control toothbrush. These results were also statistically significant (P= 0.001). Results on lingual surfaces also demonstrated statistically significantly (P< 0.001) greater plaque removal for the experimental toothbrush with an average of 53.4% more plaque removal.

Type D personality and coronary atherosclerotic plaque vulnerability: The potential mediating effect of health behavior.

PubMed

Cheng, Fangman; Lin, Ping; Wang, Yini; Liu, Guojie; Li, Ling; Yu, Huai; Yu, Bo; Zhao, Zhenjuan; Gao, Xueqin

2018-05-01

The association between type D personality and coronary plaque vulnerability has been suggested. The objective of the study was to evaluate the potential mediating effects of health behavior on the association between type D personality and plaque vulnerability in coronary artery disease (CAD) patients. A total of 319 CAD patients were assessed for type D personality and health behavior via self-administered questionnaires. The plaque vulnerability, evaluated according to characteristics, accompaniment, and outcomes of plaque, was assessed by optical coherence tomography. Regression analysis showed that type D personality was independently associated with lipid plaque (odds ratio [OR] = 2.387, p = 0.001), thin cap fibroatheroma (TCFA) (OR = 2.366, p = 0.001), rupture (OR = 2.153, p = 0.002), and lipid arc (β = -0.291, p < 0.001). Mediation analyses showed that aspects of health behavior were significant mediators of the relationship between type D personality and plaque vulnerability. Psychological stress mediated the relationship between type D and lipid plaque (p = 0.030), TCFA (p = 0.034), and rupture (p = 0.013). Living habits significantly mediated the relationship between type D and lipid plaque (p = 0.028), TCFA (p = 0.036), but not rupture (p = 0.066). Participating in activities was not a significant mediator of the relationship between type D personality and lipid plaque (p = 0.115), TCFA (p = 0.115), or rupture (p = 0.077). Health behaviors (psychological stress and living habits) may be mediators of the association between type D personality and plaque vulnerability. Copyright © 2018 Elsevier Inc. All rights reserved.

Compositional stability of a salivary bacterial population against supragingival microbiota shift following periodontal therapy.

PubMed

Yamanaka, Wataru; Takeshita, Toru; Shibata, Yukie; Matsuo, Kazuki; Eshima, Nobuoki; Yokoyama, Takeshi; Yamashita, Yoshihisa

2012-01-01

Supragingival plaque is permanently in contact with saliva. However, the extent to which the microbiota contributes to the salivary bacterial population remains unclear. We compared the compositional shift in the salivary bacterial population with that in supragingival plaque following periodontal therapy. Samples were collected from 19 patients with periodontitis before and after periodontal therapy (mean sample collection interval, 25.8 ± 2.6 months), and their bacterial composition was investigated using barcoded pyrosequencing analysis of the 16S rRNA gene. Phylogenetic community analysis using the UniFrac distance metric revealed that the overall bacterial community composition of saliva is distinct from that of supragingival plaque, both pre- and post-therapy. Temporal variation following therapy in the salivary bacterial population was significantly smaller than in the plaque microbiota, and the post-therapy saliva sample was significantly more similar to that pre-therapy from the same individual than to those from other subjects. Following periodontal therapy, microbial richness and biodiversity were significantly decreased in the plaque microbiota, but not in the salivary bacterial population. The operational taxonomic units whose relative abundances changed significantly after therapy were not common to the two microbiotae. These results reveal the compositional stability of salivary bacterial populations against shifts in the supragingival microbiota, suggesting that the effect of the supragingival plaque microbiota on salivary bacterial population composition is limited.

Effect of a new pre-brushing rinse on dental plaque removal.

PubMed

Vouros, J; Sakellari, D; Konstantinidis, A

1994-11-01

Non-prescription prebrushing rinses to facilitate dental plaque removal have been advertised in recent years. The purpose of the present study was to determine the plaque removal effectiveness of Plax (Colgate) prebrushing rinse by comparing it to a placebo solution. 19 dental students volunteered for this double blind study which consisted of 2 experimental periods. The following procedure was followed: 3 weeks after scaling and polishing, the participants abstained from oral hygiene for 3 days to allow dental plaque to accumulate. After plaque disclosing, the 4 mandibular incisors were photographed using a strictly defined technique, as described by Quirynen et al. Then the volunteers mouthrinsed for 30 s with 15 ml of a solution provided to them. Neither the volunteers nor the examiners knew which solution (test or control) was used. After mouthrinsing, the participants were allowed to brush their teeth and the remaining plaque was photographed again. During the 2nd experimental period, the same procedure was followed, and the 2nd solution was used for mouthrinsing. The effectiveness of the solutions was evaluated by comparing the proportion of dental plaque removed during the 2 experimental periods. The area of dental plaque was measured by an electronic high-precision device (planimeter). The proportion of plaque removed after rinsing with Plax was 0.40 +/- 0.23 and after rising with placebo 0.42 +/- 0.24, of the tooth surface (p = 0.962). Analysis of data by means of paired t-test between the 2 experimental periods revealed no beneficial effect regarding plaque removal when Plax was used.

Lapaquistat acetate, a squalene synthase inhibitor, changes macrophage/lipid-rich coronary plaques of hypercholesterolaemic rabbits into fibrous lesions

PubMed Central

Shiomi, M; Yamada, S; Amano, Y; Nishimoto, T; Ito, T

2008-01-01

Background and purpose: Inhibition of squalene synthesis could transform unstable, macrophage/lipid-rich coronary plaques into stable, fibromuscular plaques. We have here treated WHHLMI rabbits, a model for coronary atherosclerosis and myocardial infarction, with a novel squalene synthase inhibitor, lapaquistat acetate (TAK-475). Experimental approach: Young male WHHLMI rabbits were fed a diet supplemented with lapaquistat acetate (100 or 200 mg per kg body weight per day) for 32 weeks. Serum lipid levels were monitored every 4 weeks. After the treatment, lipoprotein lipid and coenzyme Q10 levels were assayed, and coronary atherosclerosis and xanthomas were examined histopathologically or immunohistochemically. From histopathological and immunohistochemical sections, the composition of the plaque was analysed quantitatively with computer-assisted image analysis. Xanthoma was evaluated grossly. Key results: Lapaquistat acetate decreased plasma cholesterol and triglyceride levels, by lowering lipoproteins containing apoB100. Development of atherosclerosis and xanthomatosis was suppressed. Accumulation of oxidized lipoproteins, macrophages and extracellular lipid was decreased in coronary plaques of treated animals. Treatment with lapaquistat acetate increased collagen concentration and transformed coronary plaques into fibromuscular plaques. Lapaquistat acetate also suppressed the expression of matrix metalloproteinase-1 and plasminogen activator inhibitor-1 in the plaque and increased peripheral coenzyme Q10 levels. Increased coenzyme Q10 levels and decreased very low-density lipoprotein cholesterol levels were correlated with improvement of coronary plaque composition. Conclusion and implications: Inhibition of squalene synthase by lapaquistat acetate delayed progression of coronary atherosclerosis and changed coronary atheromatous plaques from unstable, macrophage/lipid accumulation-rich, lesions to stable fibromuscular lesions. PMID:18587443

First experiences with model based iterative reconstructions influence on quantitative plaque volume and intensity measurements in coronary computed tomography angiography.

PubMed

Precht, H; Kitslaar, P H; Broersen, A; Gerke, O; Dijkstra, J; Thygesen, J; Egstrup, K; Lambrechtsen, J

2017-02-01

Investigate the influence of adaptive statistical iterative reconstruction (ASIR) and the model-based IR (Veo) reconstruction algorithm in coronary computed tomography angiography (CCTA) images on quantitative measurements in coronary arteries for plaque volumes and intensities. Three patients had three independent dose reduced CCTA performed and reconstructed with 30% ASIR (CTDI vol at 6.7 mGy), 60% ASIR (CTDI vol 4.3 mGy) and Veo (CTDI vol at 1.9 mGy). Coronary plaque analysis was performed for each measured CCTA volumes, plaque burden and intensities. Plaque volume and plaque burden show a decreasing tendency from ASIR to Veo as median volume for ASIR is 314 mm 3 and 337 mm 3 -252 mm 3 for Veo and plaque burden is 42% and 44% for ASIR to 39% for Veo. The lumen and vessel volume decrease slightly from 30% ASIR to 60% ASIR with 498 mm 3 -391 mm 3 for lumen volume and vessel volume from 939 mm 3 to 830 mm 3 . The intensities did not change overall between the different reconstructions for either lumen or plaque. We found a tendency of decreasing plaque volumes and plaque burden but no change in intensities with the use of low dose Veo CCTA (1.9 mGy) compared to dose reduced ASIR CCTA (6.7 mGy & 4.3 mGy), although more studies are warranted. Copyright © 2016 The College of Radiographers. Published by Elsevier Ltd. All rights reserved.

Semiquantitative analysis of atherosclerotic plaque using optical coherence tomography and time-of-flight secondary ion mass spectrometry

NASA Astrophysics Data System (ADS)

Korol, Renee M.; Togonu-Bickersteth, Babajide; Yang, Victor X.; Dimov, Stamen; Vatsya, Pracha; Gordon, Maggie; Vitkin, Alex; Liu, Liying; Canham, Peter; Clarke, Sharon; Lucas, Alexandra

2003-10-01

Atherosclerosis is the underlying vascular pathology that initiates arterial thromboembolic occlusions (myocardial infarctions, strokes and peripheral vessel blockage). Two imaging modalities, Optical Coherence Tomography (OCT) and Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS), were investigated for detection and compositional analysis of unstable plaque associated with plaque erosion and sudden occlusion. OCT produces high resolution images whereas mass spectrometry images provide information on the spatial distribution of chemical elements. Diseased carotid arteries taken from patients with high-risk lesions were imaged with OCT and ToF-SIMS to give molecular and metabolic information, and matched with histopathology. OCT results show clear indications of vascular remodeling by the presence of fatty acid deposits, fibrous tissue and calcifications. ToF-SIMS further characterized changes based on secondary ion topography analysis where a high 23Na/39K ratio was indicative of arterial tissue degradation and the amount of 40Ca corresponded with late stage atherosclerosis. This pilot experiment has demonstrated that in vitro OCT imaging and ToF-SIMS of diseased carotid arteries have scientific merit for targeting clinically relevant morphology and metabolic changes to compare stable and unstable plaque. These optical techniques provide complimentary metabolic and molecular information on unstable plaque, specifically cell break-down with altered ion ratios of 23Na, 39K and 40Ca.

Toward the detection of intraplaque hemorrhage in carotid artery lesions using photoacoustic imaging

NASA Astrophysics Data System (ADS)

Arabul, Mustafa Umit; Heres, Maarten; Rutten, Marcel C. M.; van Sambeek, Marc R.; van de Vosse, Frans N.; Lopata, Richard G. P.

2017-04-01

Photoacoustic imaging (PAI) may have the ability to reveal the composition and the anatomical structure of carotid plaques, which determines its mechanical properties and vulnerability. We used PAI and plane wave ultrasound (PUS) imaging to obtain three-dimensional (3-D) images of endarterectomy samples ex vivo and compared the results with histology to investigate the potential of PAI-based identification of intraplaque hemorrhage. Seven carotid plaque samples were obtained from patients undergoing carotid endarterectomy and imaged with a fully integrated hand-held photoacoustic (PA) probe, consisting of a pulsed diode laser (tpulse=130 ns, Epulse=1 mJ, λ=808 nm) and a linear array transducer (fc=7.5 MHz). The samples were rotated 360 deg with 10 deg steps, and data were spatially compounded to obtain complete 3-D images of the plaques. Areas of high absorption in the 3-D datasets were identified and compared to histological data of the plaques. Data in six out of seven endarterectomy samples revealed the presence of intraplaque hemorrhages that were not visible in the PUS images. Due to the noninvasive nature of PAI, this ex vivo study may elucidate preclinical studies toward the in vivo, noninvasive, vulnerability assessment of the atherosclerotic carotid plaque.

Activation of activator protein 2 alpha by aspirin alleviates atherosclerotic plaque growth and instability in vivo

PubMed Central

Yang, Jing-Jing; Li, Peng; Wang, Fu; Liang, Wen-Jing; Ma, Hui; Chen, Yuan; Ma, Zhi-Min; Li, Quan-Zhong; Peng, Qi-Sheng; Zhang, Yun; Wang, Shuang-Xi

2016-01-01

Aims Aspirin has been used for the secondary prevention and treatment of cardiovascular disease for several decades. We investigated the roles of transcriptional factor activator protein 2α (AP-2α) in the beneficial effects of aspirin in the growth and vulnerability of atherosclerotic plaque. Methods and Results In mice deficient of apolipoprotein E (Apoe-/-), aspirin (20, 50 mg/kg/day) suppressed the progression of atherosclerosis in aortic roots and increased the plaque stability in carotid atherosclerotic plaques induced by collar-placement. In vivo lentivirus-mediated RNA interference of AP-2α reversed the inhibitory effects of aspirin on atherosclerosis in Apoe-/- mice. Mechanically, aspirin increased AP-2α phosphorylation and its activity, upregulated IkBα mRNA and protein levels, and reduced oxidative stress in cultured vascular smooth muscle cells. Furthermore, deficiency of AP-2α completely abolished aspirin-induced upregulation of IkBα levels and inhibition of oxidative stress in Apoe-/- mice. Clinically, conventional doses of aspirin increased AP-2α phosphorylation and IkBα protein expression in humans subjects. Conclusion Aspirin activates AP-2α to upregulate IkBα gene expression, resulting in attenuations of plaque development and instability in atherosclerosis. PMID:27391154

Demographics and Characterization of 10,282 Randall Plaque-Related Kidney Stones

PubMed Central

Letavernier, Emmanuel; Vandermeersch, Sophie; Traxer, Olivier; Tligui, Mohamed; Baud, Laurent; Ronco, Pierre; Haymann, Jean-Philippe; Daudon, Michel

2015-01-01

Abstract Renal stone incidence has progressively increased in industrialized countries, but the implication of Randall plaque in this epidemic remains unknown. Our objectives were to determine whether the prevalence of Randall plaque-related stones increased during the past decades after having analyzed 30,149 intact stones containing mainly calcium oxalate since 1989 (cross-sectional study), and to identify determinants associated with Randall plaque-related stones in patients (case–control study). The proportion of Randall plaque-related stones was assessed over 3 time periods: 1989–1991, 1999–2001, and 2009–2011. Moreover, we analyzed clinical and biochemical parameters of 105 patients affected by calcium oxalate stones, with or without plaque. Of 30,149 calcium oxalate stones, 10,282 harbored Randall plaque residues (34.1%). The prevalence of Randall plaque-related stones increased dramatically during the past years. In young women, 17% of calcium oxalate stones were associated with Randall plaque during the 1989–1991 period, but the proportion rose to 59% 20 years later (P < 0.001). Patients with plaques experienced their first stone-related event earlier in life as compared with those without plaque (median age 26 vs 34 years, P = 0.02), had increased ionized serum calcium levels (P = 0.04), and increased serum osteocalcin (P = 0.001) but similar 25-hydroxyvitamin D levels. The logistic regression analysis showed that age (odds ratio [OR] 0.96, confidence interval [CI] 0.926–0.994, P = 0.02), weight (OR 0.97, CI 0.934–0.997, P = 0.03), and osteocalcin serum levels (OR 1.12, CI 1.020–1.234, P = 0.02) were independently associated with Randall plaque. The prevalence of the FokI f vitamin D receptor polymorphism was higher in patients with plaque (P = 0.047). In conclusion, these findings point to an epidemic of Randall plaque-associated renal stones in young patients, and suggest a possible implication of altered vitamin D response. PMID:25761176

MRI of plaque characteristics and relationship with downstream perfusion and cerebral infarction in patients with symptomatic middle cerebral artery stenosis.

PubMed

Lu, Shan-Shan; Ge, Song; Su, Chun-Qiu; Xie, Jun; Mao, Jian; Shi, Hai-Bin; Hong, Xun-Ning

2017-10-30

Intracranial plaque characteristics are associated with stroke events. Differences in plaque features may explain the disconnect between stenosis severity and the presence of ischemic stroke. To investigate the relationship between plaque characteristics and downstream perfusion changes, and their contribution to the occurrence of cerebral infarction beyond luminal stenosis. Case control. Forty-six patients with symptomatic middle cerebral artery (MCA) stenosis (with acute cerebral infarction, n = 30; without acute cerebral infarction, n = 16). 3.0T with 3D turbo spin echo sequence (3D-SPACE). Luminal stenosis grade, plaque features including lesion T 2 and T 1 hyperintense components, plaque enhancement grade, and plaque distribution were assessed. Brain perfusion was evaluated on mean transient time maps based on the Alberta Stroke Program Early CT score (MTT-ASPECTS). Plaque features, grade of luminal stenosis, and MTT-ASPECTS were compared between two groups. The association between plaque features and MTT-ASPECTS were assessed using Spearman's correlation analysis. Multivariate logistic regression and receiver operating characteristic (ROC) curves were constructed to assess the effect of significant variables alone and their combination in determining the occurrence of cerebral infarction. Stronger enhanced plaques were associated with downstream lower MTT-ASPECTS (P = 0.010). Plaque enhancement grade (P = 0.039, odds ratio [OR] 5.9, 95% confidence interval [CI] 1.1-32) and MTT-ASPECTS (P = 0.003, OR 2.6, 95% CI 1.4-4.7) were associated with a recent cerebral infarction, whereas luminal stenosis grade was not (P = 0.128). The combination of MTT-ASPECTS and plaque enhancement grade provided incremental information beyond luminal stenosis grade alone. The area under the receiver operating characteristic curve (AUC) improved from 0.535 to 0.921 (P < 0.05). Strongly enhanced plaques are associated with a higher likelihood of downstream perfusion impairment. Plaque enhancement and perfusion evaluation may play a complementary role to luminal stenosis in determining the occurrence of acute cerebral infarction. 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017. © 2017 International Society for Magnetic Resonance in Medicine.

Identification of Mature Atherosclerotic Plaque Proteome Signatures Using Data-Independent Acquisition Mass Spectrometry.

PubMed

Hansmeier, Nicole; Buttigieg, Josef; Kumar, Pankaj; Pelle, Shaneen; Choi, Kyoo Yoon; Kopriva, David; Chao, Tzu-Chiao

2018-01-05

Atherosclerosis is a chronic inflammatory disease with complex pathobiology and one of the most common causes of cardiovascular events. The process is characterized by complex vascular remodeling processes that require the actions of numerous proteins. The composition of atherosclerotic plaque is increasingly recognized as a major factor governing the occurrence of cardiovascular or neurological symptoms. To gain deeper insights into the composition of atherosclerotic plaques, we created quantitative proteome profiles of advanced plaque tissues of six male patients undergoing carotid endarterectomy for stroke prevention. Using a quantitative, data-independent proteome approach, we identified 4181 proteins with an average protein coverage of 45%. An analysis of the quantitative composition of the tissue revealed key players of vascular remodeling processes. Moreover, compared with proximal arterial tissue, 20 proteins in mature plaques were enriched, whereas 52 proteins were found in lower quantities. Among the proteins with increased abundance were prominent extracellular matrix proteins such as biglycan and lumican, whereas cytoskeletal markers for contractile smooth muscle cells (SMCs) were decreased. Taken together, this study provides the most comprehensive quantitative assessment of mature human plaque tissue to date, which indicates a central role of SMCs in the structure of advanced atherosclerotic plaques.

Spatial distribution of osteoblast-specific transcription factor Cbfa1 and bone formation in atherosclerotic arteries.

PubMed

Bobryshev, Yuri V; Killingsworth, Murray C; Lord, Reginald S A

2008-08-01

The mechanisms of ectopic bone formation in arteries are poorly understood. Osteoblasts might originate either from stem cells that penetrate atherosclerotic plaques from the blood stream or from pluripotent mesenchymal cells that have remained in the arterial wall from embryonic stages of the development. We have examined the frequency of the expression and spatial distribution of osteoblast-specific factor-2/core binding factor-1 (Osf2/Cbfa1) in carotid and coronary arteries. Cbfa1-expressing cells were rarely observed but were found in all tissue specimens in the deep portions of atherosclerotic plaques under the necrotic cores. The deep portions of atherosclerotic plaques under the necrotic cores were characterized by the lack of capillaries of neovascularization. In contrast, plaque shoulders, which were enriched by plexuses of neovascularization, lacked Cbfa1-expressing cells. No bone formation was found in any of the 21 carotid plaques examined and ectopic bone was observed in only two of 12 coronary plaques. We speculate that the sparse invasion of sprouts of neovascularization into areas underlying the necrotic cores, where Cbfa1-expressing cells reside, might explain the rarity of events of ectopic bone formation in the arterial wall. This study has also revealed that Cbfa1-expressing cells contain alpha-smooth muscle actin and myofilaments, indicating their relationship with arterial smooth muscle cells.

From Lipid Retention to Immune-Mediate Inflammation and Associated Angiogenesis in the Pathogenesis of Atherosclerosis.

PubMed

Usman, Ammara; Ribatti, Domenico; Sadat, Umar; Gillard, Jonathan H

2015-08-26

Atherosclerosis is a leading cause of mortality and long-term morbidity worldwide. It is a lipoprotein-driven disease that leads to plaque formation at focal areas in the arterial blood vessels through intimal inflammation, necrosis, fibrosis, and calcification. Adventitial and intimal angiogenesis contributes to the progression of intimal hyperplasia and the development of a necrotic core. The volatile nature of an atheromatous plaque is responsible for approximately 60% of symptomatic carotid artery diseases and about 75% of acute coronary events. In this review the pathogenesis of atherosclerosis is discussed from the initial step of lipid retention to advanced stages of immune-mediate inflammation and associated angiogenesis. Mechanisms of plaque rupture are also discussed.

Genotoxic assessment of chlorhexidine mouthwash on exfoliated buccal epithelial cells in chronic gingivitis patients

PubMed Central

Khan, Saif; Khan, Asad Ullah; Hasan, Sadaf

2016-01-01

Background: Chlorhexidine (CHX) is the gold standard of all chemical plaque control agents and the most commonly prescribed mouthwash. However, several studies have shown cytotoxic and genotoxic effects of CHX on various eukaryotic cells. In this study, we have used micronuclei as a biomarker of DNA damage in buccal epithelial cells of chronic gingivitis patients who were given adjunct 0.2% CHX for plaque control. Materials and Methods: Chronic gingivitis patients who were exclusively on mechanical plaque control methods were taken as control (Group A) (n = 101), and chronic gingivitis patients who along with mechanical plaque control measures were taking 0.2% chlorhexidine mouthwash as adjunct were taken as cases (Group B) (n = 255). The Group B was further divided into 5 subgroups (B1, B2, B3, B4, B5) (n = 51) on increasing duration of usage of CHX from ≤1 week to 24 weeks. Buccal epithelial cells were gently scrapped from the buccal mucosa using soft toothbrush. The epithelial cells were collected in buffer solution and centrifuged at 8000 rpm for 5 min. The buccal epithelial cells were air dried, fixed, and stained with 5% Giemsa stain on preheated glass microscopic slides and observed under microscope to screen 2000 nucleated cells per individual for number of micronucleated cells and micronuclei as genotoxic measure. Results: The mean number of micronucleated cells was found to be 0.41 ± 0.71 for Group A as compared values ranging from 1.65 ± 2.09 (Group B1) to 11.7 ± 1.87 (Group B5) in different subgroups of Group B, and similarly, the mean number of micronuclei was found to be 0.48 ± 0.80 for Group A as compared to values ranging from 2.57 ± 1.64 (Group B1) to 14.5 ± 2.49 (Group B5) in different subgroups of Group B using analysis of variance (P < 0.001). Conclusion: We conclude that CHX mouthwash is genotoxic to buccal epithelial cells and there is incremental trend in genotoxicity as the duration of usage is increased. PMID:29238137

Assessment of sex differences in plaque morphology by coronary computed tomography angiography--are men and women the same?

PubMed

Grunau, Gilat L; Ahmadi, Amir; Rezazadeh, Saman; Faraji, Reza; Amid, Sima; O'Connell, Tim; Heilbron, Brett; Leipsic, Jonathon; Taylor, Carolyn M

2014-02-01

The objective of this study was to assess whether sex differences exist in plaque burden and plaque subtype as assessed by coronary computed tomography angiography (CCTA). The study cohort included 937 consecutive patients who underwent CCTA between 2008 and 2010. Stenosis was quantified using the Society of Cardiovascular Computed Tomography stenosis grading scale and a total stenosis score (TSS) was generated. Plaque morphology (PM) was reported as predominantly calcified (CP), noncalcified (NCP), or mixed (MP) plaque, and CP, NCP, and MP percentages were calculated. On multivariate analysis, men were significantly more likely to have plaque (65.9% of men vs. 44.6% of women, p<0.001), at least one segment with ≥50% stenosis (22.7% of men vs. 10.3% of women, p<0.001) and higher TSS (mean score=2.81 for men vs. 1.58 for women, p<0.001). Sex was the strongest predictor in all models (odds ratio [OR]=2.55, 95% confidence interval [CI] 1.78-3.67, p<0.001 for any plaque; OR=2.48, 95% CI 1.48-4.16, p<0.01 for segments with ≥50% stenosis; β=1.46, 95% CI 0.69-2.22, p<0.001 for TSS). Among patients with coronary plaque present, no significant sex differences in PM were found. Sex was the strongest risk factor for the presence and extent of plaque. Significant sex differences in PM did not exist.

Amyloid load and neural elements in Alzheimer's disease and nondemented individuals with high amyloid plaque density.

PubMed

Mochizuki, A; Peterson, J W; Mufson, E J; Trapp, B D

1996-11-01

The amyloid burden and relationship between amyloid deposits and neural elements were investigated in sections of prefrontal neocortex from eight Alzheimer's disease (AD) patients and four age-matched nondemented controls with high amyloid plaque density (HPND). Computer-based image analysis revealed that the total area occupied by betaA4 immunoreactivity was significantly greater (P < 0.031) in AD (27.1%) than in HPND (14.5%) sections. The total betaA4-positive area occupied by nondiffuse plaques was significantly greater (P < 0.05) in AD (13.6%) than in HPND (5.2%) sections. The percentage of diffuse (DPs) and nondiffuse plaques (NDPs) which contained neurons, astrocytes, microglia, dystrophic neurites, and amyloid precursor protein (APP) was also determined. The frequency of association between betaA4 and these neural elements was similar between AD and HPND cases in both diffuse and nondiffuse plaques. Forty percent of DPs in AD and HPND sections contained neuronal perikarya. Microglia, dystrophic neurites, and APP were detected in most nondiffuse plaques in both AD and HPND sections. While astrocyte cell bodies were not present in either diffuse or nondiffuse plaques, their processes were detected in most. These findings indicate that amyloid deposition and nondiffuse plaques are greater in AD than in HPND sections. The association between microglia and nondiffuse plaques supports the hypothesis that these resident immune cells participate in aggregation and redistribution of amyloid deposits and possibly formation of dystrophic neurites.

The NF-κB pathway: regulation of the instability of atherosclerotic plaques activated by Fg, Fb, and FDPs.

PubMed

Cao, Yongjun; Zhou, Xiaomei; Liu, Huihui; Zhang, Yanlin; Yu, Xiaoyan; Liu, Chunfeng

2013-11-01

Recently, the molecular mechanism responsible for the instability of atherosclerotic plaques has gradually become a hot topic among researchers and clinicians. Matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) play an important role in the processes of formation and development of atherosclerosis. In this study, we established and employed the transwell co-culture system of rabbit aortic endothelial cells and smooth muscle cells to explore the relationship between fibrin (Fb), fibrinogen (Fg), and/or their degradation products (FDPs) in relation to the instability of atherosclerotic plaques; meanwhile, we observed the effects of Fg, Fb, and FDPs on the mRNA levels of MMPs and VEGF as well as on the activation of nuclear factor-kappa B (NF-κB). We concluded that Fb, Fg, and FDPs are involved in the progression of the instability of atherosclerotic plaques via increasing the expression of MMPs and VEGF. This effect might be mediated by the NF-кB pathway.

Assessment of plaque vulnerability in atherosclerosis via intravascular photoacoustic imaging of targeted liposomal ICG J-aggregates (Conference Presentation)

NASA Astrophysics Data System (ADS)

Harris, Justin T.; Dumani, Diego S.; Cook, Jason R.; Sokolov, Konstantin V.; Emelianov, Stanislav Y.; Homan, Kimberly A.

2017-03-01

While molecular and cellular imaging can be used to visualize the conventional morphology characteristics of vulnerable plaques, there is a need to monitor other physiological factors correlated with high rupture rates; a high M1 activated macrophage concentration is one such indicator of high plaque vulnerability. Here, we present a molecularly targeted contrast agent for intravascular photoacoustic (IVPA) imaging consisting of liposomes loaded with indocyanine green (ICG) J-aggregates with high absorption at 890 nm, allowing for imaging in the presence of blood. This "Lipo-ICG" was targeted to a biomarker of M1 activated macrophages in vulnerable plaques: folate receptor beta (FRβ). The targeted liposomes accumulate in plaques through areas of endothelial dysfunction, while the liposome encapsulation prevents nonspecific interaction with lipids and endothelium. Lipo-ICG specifically interacts with M1 activated macrophages, causing a spectral shift and change in the 890/780 nm photoacoustic intensity ratio upon breakdown of J-aggregates. This sensing mechanism enables assessment of the M1 activated macrophage concentration, providing a measure of plaque vulnerability. In a pilot in vivo study utilizing ApoE deficient mouse models of atherosclerosis, diseased mice showed increased uptake of FRβ targeted Lipo-ICG in the heart and arteries vs. normal mice. Likewise, targeted Lipo-ICG showed increased uptake vs. two non-targeted controls. Thus, we successfully synthesized a contrast agent to detect M1 activated macrophages in high risk atherosclerotic plaques and exhibited targeting both in vitro and in vivo. This biocompatible agent could enable M1 macrophage detection, allowing better clinical decision making in treatment of atherosclerosis.

Step down Vascular Calcification Analysis using State-of-the-Art Nanoanalysis Techniques

PubMed Central

Curtze, Sven C.; Kratz, Marita; Steinert, Marian; Vogt, Sebastian

2016-01-01

New insights into the architecture and formation mechanisms of calcific lesions down to the nanoscale open a better understanding of atherosclerosis and its pathogenesis. Scanning electron – and atomic force microscope based nano-analytical characterization techniques were adapted to the assessment of an ex-vivo calcified coronary artery. Human atherosclerotic tissue and bone tissue reside a typical chemistry of Magnesium and Sodium rich Calcium phosphates, identified as whitlockite and Calcium apatite, respectively. Despite the obvious similarities in both chemistry and crystallography, there are also clear differences between calcified vascular tissue and bone such as the highly oriented growth in bone, revealing meso-crystal character, as opposed to the anisotropic character of calcified vascular lesions. While the grain size in vascular calcified plaques is in the range of nanometers, the grain size in bone appears larger. Spherical calcific particles present in both the coronary artery wall and embedded in plaques reveal concentric layers with variations in both organic content and degree of hydration. PMID:26980376

Step down Vascular Calcification Analysis using State-of-the-Art Nanoanalysis Techniques.

PubMed

Curtze, Sven C; Kratz, Marita; Steinert, Marian; Vogt, Sebastian

2016-03-16

New insights into the architecture and formation mechanisms of calcific lesions down to the nanoscale open a better understanding of atherosclerosis and its pathogenesis. Scanning electron - and atomic force microscope based nano-analytical characterization techniques were adapted to the assessment of an ex-vivo calcified coronary artery. Human atherosclerotic tissue and bone tissue reside a typical chemistry of Magnesium and Sodium rich Calcium phosphates, identified as whitlockite and Calcium apatite, respectively. Despite the obvious similarities in both chemistry and crystallography, there are also clear differences between calcified vascular tissue and bone such as the highly oriented growth in bone, revealing meso-crystal character, as opposed to the anisotropic character of calcified vascular lesions. While the grain size in vascular calcified plaques is in the range of nanometers, the grain size in bone appears larger. Spherical calcific particles present in both the coronary artery wall and embedded in plaques reveal concentric layers with variations in both organic content and degree of hydration.

Arsenic rich iron plaque on macrophyte roots--an ecotoxicological risk?

PubMed

Taggart, M A; Mateo, R; Charnock, J M; Bahrami, F; Green, A J; Meharg, A A

2009-03-01

Arsenic is known to accumulate with iron plaque on macrophyte roots. Three to four years after the Aznalcóllar mine spill (Spain), residual arsenic contamination left in seasonal wetland habitats has been identified in this form by scanning electron microscopy. Total digestion has determined arsenic concentrations in thoroughly washed 'root+plaque' material in excess of 1000 mg kg(-1), and further analysis using X-ray absorption spectroscopy suggests arsenic exists as both arsenate and arsenite. Certain herbivorous species feed on rhizomes and bulbs of macrophytes in a wide range of global environments, and the ecotoxicological impact of consuming arsenic rich iron plaque associated with such food items remains to be quantified. Here, greylag geese which feed on Scirpus maritimus rhizome and bulb material in areas affected by the Aznalcóllar spill are shown to have elevated levels of arsenic in their feces, which may originate from arsenic rich iron plaque.

The presence of Helicobacter pylori in dental plaque of children and their parents: is it related to their periodontal status and oral hygiene?

PubMed

Tsami, A; Petropoulou, P; Kafritsa, Y; Mentis, Y A; Roma-Giannikou, E

2011-12-01

To investigate the possible presence of H. pylori in subgingival dental plaque of children with upper gastrointestinal symptoms, as well as of their parents' and to detect any association between the presence of H. pylori and oral hygiene together with the periodontal status of children and their parents. The study comprised of 35 children with upper gastrointestinal symptoms, aged 4 to 14 years and 45 family members (mothers and/or fathers). Gastric biopsies were collected from all children for CLO-test, histology and culture. Serology was used to assess the H. pylori infection status of their parents. Before endoscopy, subgingival dental plaque from children and their parents were collected from 4 healthy and 4 diseased sites, and the clinical indices (gingival index, plaque index, bleeding on probing, pocket depth, loss of clinical attachment) after plaque collection were recorded. The Chi-square test was performed to investigate possible differences between children and their parents and logistic regression analysis was used to evaluate the association of parental infection status with that of children. 15 out of 35 children (42.86%) were found H. pylori-positive. In 6 out of the 15 infected children (40%) H. pylori was also identified in their subgingival plaque samples, as well as in one among the 20 non infected children. The presence of H. pylori in dental plaque was significantly associated with its presence in the gastric antrum (p=0.0274). H. pylori was identified in the dental plaque of 7 mothers corresponding to children with positive PCR in their dental plaque and of 4 fathers (one corresponding with his child found H. pylori positive in dental plaque). Children who had H. pylori identified in their dental plaque belonged to families with members also having H. pylori in dental plaque. No significant relationship between periodontal clinical parameters and detection of H. pylori in dental plaque in both children and their parents was found. However, the presence of H. pylori in the subgingival plaque samples was significantly correlated with the parental diseased sites (p=0.02). H. pylori was detected in subgingival dental plaque of children and their families, possibly acting as a "reservoir" contributing to the intra-familial spread. Efficient oral hygiene and healthy periodontal status could reduce this transmission.

Systems analysis of thrombus formation

PubMed Central

Diamond, Scott L.

2016-01-01

The systems analysis of thrombosis seeks to quantitatively predict blood function in a given vascular wall and hemodynamic context. Relevant to both venous and arterial thrombosis, a Blood Systems Biology approach should provide metrics for rate and molecular mechanisms of clot growth, thrombotic risk, pharmacological response, and utility of new therapeutic targets. As a rapidly created multicellular aggregate with a polymerized fibrin matrix, blood clots result from hundreds of unique reactions within and around platelets propagating in space and time under hemodynamic conditions. Coronary artery thrombosis is dominated by atherosclerotic plaque rupture, complex pulsatile flows through stenotic regions producing high wall shear stresses, and plaque-derived tissue factor driving thrombin production. In contrast, venous thrombosis is dominated by stasis or depressed flows, endothelial inflammation, white blood cell-derived tissue factor, and ample red blood cell incorporation. By imaging vessels, patient-specific assessment using computational fluid dynamics provides an estimate of local hemodynamics and fractional flow reserve. High dimensional ex vivo phenotyping of platelet and coagulation can now power multiscale computer simulations at the subcellular to cellular to whole vessel scale of heart attacks or strokes. Additionally, an integrated systems biology approach can rank safety and efficacy metrics of various pharmacological interventions or clinical trial designs. PMID:27126646

Quantification In Situ of Crystalline Cholesterol and Calcium Phosphate Hydroxyapatite in Human Atherosclerotic Plaques by Solid-State Magic Angle Spinning NMR

PubMed Central

Guo, Wen; Morrisett, Joel D.; DeBakey, Michael E.; Lawrie, Gerald M.; Hamilton, James A.

2010-01-01

Because of renewed interest in the progression, stabilization, and regression of atherosclerotic plaques, it has become important to develop methods for characterizing structural features of plaques in situ and noninvasively. We present a nondestructive method for ex vivo quantification of 2 solid-phase components of plaques: crystalline cholesterol and calcium phosphate salts. Magic angle spinning (MAS) nuclear magnetic resonance (NMR) spectra of human carotid endarterectomy plaques revealed 13C resonances of crystalline cholesterol monohydrate and a 31P resonance of calcium phosphate hydroxyapatite (CPH). The spectra were obtained under conditions in which there was little or no interference from other chemical components and were suitable for quantification in situ of the crystalline cholesterol and CPH. Carotid atherosclerotic plaques showed a wide variation in their crystalline cholesterol content. The calculated molar ratio of liquid-crystalline cholesterol to phospholipid ranged from 1.1 to 1.7, demonstrating different capabilities of the phospholipids to reduce crystallization of cholesterol. The spectral properties of the phosphate groups in CPH in carotid plaques were identical to those of CPH in bone. 31P MAS NMR is a simple, rapid method for quantification of calcium phosphate salts in tissue without extraction and time-consuming chemical analysis. Crystalline phases in intact atherosclerotic plaques (ex vivo) can be quantified accurately by solid-state 13C and 31PMAS NMR spectroscopy. PMID:10845882

Optimization of dual-wavelength intravascular photoacoustic imaging of atherosclerotic plaques using Monte Carlo optical modeling

NASA Astrophysics Data System (ADS)

Dana, Nicholas; Sowers, Timothy; Karpiouk, Andrei; Vanderlaan, Donald; Emelianov, Stanislav

2017-10-01

Coronary heart disease (the presence of coronary atherosclerotic plaques) is a significant health problem in the industrialized world. A clinical method to accurately visualize and characterize atherosclerotic plaques is needed. Intravascular photoacoustic (IVPA) imaging is being developed to fill this role, but questions remain regarding optimal imaging wavelengths. We utilized a Monte Carlo optical model to simulate IVPA excitation in coronary tissues, identifying optimal wavelengths for plaque characterization. Near-infrared wavelengths (≤1800 nm) were simulated, and single- and dual-wavelength data were analyzed for accuracy of plaque characterization. Results indicate light penetration is best in the range of 1050 to 1370 nm, where 5% residual fluence can be achieved at clinically relevant depths of ≥2 mm in arteries. Across the arterial wall, fluence may vary by over 10-fold, confounding plaque characterization. For single-wavelength results, plaque segmentation accuracy peaked at 1210 and 1720 nm, though correlation was poor (<0.13). Dual-wavelength analysis proved promising, with 1210 nm as the most successful primary wavelength (≈1.0). Results suggest that, without flushing the luminal blood, a primary and secondary wavelength near 1210 and 1350 nm, respectively, may offer the best implementation of dual-wavelength IVPA imaging. These findings could guide the development of a cost-effective clinical system by highlighting optimal wavelengths and improving plaque characterization.

Simultaneous amplification of two bacterial genes: more reliable method of Helicobacter pylori detection in microbial rich dental plaque samples.

PubMed

Chaudhry, Saima; Idrees, Muhammad; Izhar, Mateen; Butt, Arshad Kamal; Khan, Ayyaz Ali

2011-01-01

Polymerase Chain reaction (PCR) assay is considered superior to other methods for detection of Helicobacter pylori (H. pylori) in oral cavity; however, it also has limitations when sample under study is microbial rich dental plaque. The type of gene targeted and number of primers used for bacterial detection in dental plaque samples can have a significant effect on the results obtained as there are a number of closely related bacterial species residing in plaque biofilm. Also due to high recombination rate of H. pylori some of the genes might be down regulated or absent. The present study was conducted to determine the frequency of H. pylori colonization of dental plaque by simultaneously amplifying two genes of the bacterium. One hundred dental plaque specimens were collected from dyspeptic patients before their upper gastrointestinal endoscopy and presence of H. pylori was determined through PCR assay using primers targeting two different genes of the bacterium. Eighty-nine of the 100 samples were included in final analysis. With simultaneous amplification of two bacterial genes 51.6% of the dental plaque samples were positive for H. pylori while this prevalence increased to 73% when only one gene amplification was used for bacterial identification. Detection of H. pylori in dental plaque samples is more reliable when two genes of the bacterium are simultaneously amplified as compared to one gene amplification only.

Carotid Plaque Morphology in Asymptomatic Patients with and without Metabolic Syndrome.

PubMed

Cury, Marcus Vinícius Martins; Presti, Calógero; Bonadiman, Suellen Stevam Timotheo; Casella, Ivan Benaduce; Benabou, Joseph Elias; da Silva, Erasmo Simão; de Luccia, Nelson; Puech-Leão, Pedro

2017-02-01

The aim of this study was to determine the impact of metabolic syndrome (MetS) on the morphology of carotid plaques, as evaluated using duplex ultrasound (DUS) with computer-assisted analysis. In this cross-sectional observational study, we analyzed 148 carotid artery plaques in asymptomatic patients. Data were obtained via clinical and laboratory examinations, and DUS was performed by a single operator. All plaques were scanned in a longitudinal fashion, and the best segment was selected, recorded, and evaluated using dedicated software. The main software-based analyses included gray-scale median (GSM) measurements and carotid plaque morphology histograms. MetS was identified in 51.8% of patients. Comparisons of patients with MetS and patients without MetS indicated that the former patients used more classes of antihypertensive drugs (2.49 vs. 1.93; P = 0.004) and were treated with statins for a longer period (71.08 vs. 49.17 months; P = 0.003). Most patients of both types exhibited moderate carotid artery stenosis ranging from 50% to 69% (n = 62; 37.3%), and MetS was not associated with an increased prevalence of severe carotid artery stenosis. The mean GSM was greater in the MetS group than in the non-MetS group (74.18 vs. 61.63; P = 0.012). The histogram analysis revealed that there were lower quantities of blood and fat (2.91 vs. 3.88; P = 0.006; 10.21 vs. 15.08; P = 0.004, respectively) and more fibrous tissue (19.93 vs. 14.55; P = 0.015) in the carotid plaques of patients with MetS than in the carotid plaques of patients without MetS. The present study demonstrated that MetS did not affect the stenosis grade or did it lead to unstable carotid plaques. Copyright © 2016 Elsevier Inc. All rights reserved.

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

Badiyan, Shahed N.; Rao, Rajesh C.; Apicelli, Anthony J.

Purpose: To assess the impact on local tumor control of intraoperative ultrasonographic plaque visualization and selective application of transpupillary thermotherapy (TTT) in the treatment of posterior uveal melanoma with iodine-125 (I-125) episcleral plaque brachytherapy (EPB). Methods and Materials: Retrospective analysis of 526 patients treated with I-125 EPB for posterior uveal melanoma. Clinical features, dosimetric parameters, TTT treatments, and local tumor control outcomes were recorded. Statistical analysis was performed using Cox proportional hazards and Kaplan-Meier life table method. Results: The study included 270 men (51%) and 256 women (49%), with a median age of 63 years (mean, 62 years; range, 16-91more » years). Median dose to the tumor apex was 94.4 Gy (mean, 97.8; range, 43.9-183.9) and to the tumor base was 257.9 Gy (mean, 275.6; range, 124.2-729.8). Plaque tilt >1 mm away from the sclera at plaque removal was detected in 142 cases (27%). Supplemental TTT was performed in 72 patients (13.7%). One or 2 TTT sessions were required in 71 TTT cases (98.6%). After a median follow-up of 45.9 months (mean, 53.4 months; range, 6-175 months), local tumor recurrence was detected in 19 patients (3.6%). Local tumor recurrence was associated with lower dose to the tumor base (P=.02). Conclusions: Ultrasound-guided plaque localization of I-125 EPB is associated with excellent local tumor control. Detection of plaque tilt by ultrasonography at plaque removal allows supplemental TTT to be used in patients at potentially higher risk for local recurrence while sparing the majority of patients who are at low risk. Most patients require only 1 or 2 TTT sessions.« less

Subclinical carotid atherosclerosis in patients with chronic obstructive pulmonary disease: a meta-analysis of literature studies.

PubMed

Ambrosino, Pasquale; Lupoli, Roberta; Cafaro, Giovanni; Iervolino, Salvatore; Carone, Mauro; Pappone, Nicola; Di Minno, Matteo Nicola Dario

2017-09-01

Chronic obstructive pulmonary disease (COPD) patients have an increased cardiovascular (CV) morbidity and mortality. Common carotid intima-media thickness (CCA-IMT) and carotid plaques are surrogate markers of subclinical atherosclerosis and predictors of CV events. We performed a meta-analysis to evaluate the association between COPD and subclinical atherosclerosis. Studies evaluating the impact of COPD on CCA-IMT and on the prevalence of carotid plaques were systematically searched. Twenty studies (2082 COPD patients and 4844 controls) were included, 12 studies with data on CCA-IMT (13 data-sets on 1180 COPD patients and 2312 controls) and 12 studies reporting on the prevalence of carotid plaques (1231 COPD patients and 4222 controls). Compared to controls, COPD patients showed a significantly higher CCA-IMT (mean difference [MD]: 0.201 mm; 95%CI: 0.142, 0.260; p < .001), and an increased prevalence of carotid plaques (Odds Ratio [OR]: 2.503; 95%CI: 1.333, 2.175; p < .0001). Meta-regression models showed a direct association between disease severity [as expressed by Global Initiative for Chronic Obstructive Lung Disease (GOLD) class] and the difference in the risk of carotid plaques presence between COPD patients and controls. COPD is significantly associated with subclinical atherosclerosis. These findings may be useful to plan adequate CV prevention strategies. Key messages COPD patients show a higher CCA-IMT and an increased prevalence of carotid plaques compared with controls. A more severe pulmonary disease is associated with a higher prevalence of carotid plaques in COPD patients. Screening for subclinical atherosclerosis may be worthy in COPD patients to plan specific prevention strategies.

Prediction of periodontopathic bacteria in dental plaque of periodontal healthy subjects by measurement of volatile sulfur compounds in mouth air.

PubMed

Kishi, Mitsuo; Ohara-Nemoto, Yuko; Takahashi, Masahiro; Kishi, Kayo; Kimura, Shigenobu; Aizawa, Fumie; Yonemitsu, Masami

2013-03-01

The aim of this study was to determine whether measurements of volatile sulfur compounds (VSCs) are useful to predict colonization of periodontopathic bacteria. For this purpose, we assessed the relationships among distributions of 4 species of periodontopathic bacteria in tongue coating and dental plaque, oral conditions including VSC concentration in mouth air, and smoking habit of periodontal healthy young subjects. The subjects were 108 young adults (mean age, 23.5±2.56 years) without clinical periodontal pockets. Information regarding smoking habit was obtained by interview. After VSC concentration in mouth, air was measured with a portable sulfide monitor (Halimeter(®)), non-stimulated saliva flow and dental caries status were assessed, and tongue coating and dental plaque samples were collected from the subjects. The tongue coating samples were weighed to determine the amount. The colonization of Porphyromonas gingivalis, Tannerella forsythia, Prevotella intermedia, and Treponema denticola in both tongue coating and plaque samples was investigated using species-specific polymerase chain reaction assays. Significant relationships were observed between the colonization of periodontopathic bacteria in tongue coating and plaque samples, especially that of P. gingivalis. VSC concentration showed the most significant association with colonization of P. gingivalis in both tongue coating and dental plaque. Logistic regression analysis demonstrated that the adjusted partial correlation coefficient [Exp(B)] values for VSC concentration with the colonization of P. gingivalis, P. intermedia, and T. denticola in dental plaque were 135, 35.4 and 10.4, respectively. In addition, smoking habit was also shown to be a significant variable in regression models [Exp(B)=6.19, 8.92 and 2.53, respectively]. Therefore, receiver operating characteristic analysis was performed to predict the colonization of periodontal bacteria in dental plaque in the subjects divided by smoking habit. Based on our results, we found cut-off values that indicated likelihood ratios (LR) within the efficient range for positive findings in both groups. The present results demonstrated that measurement of VSC concentration in mouth air is a useful method to predict the presence of colonization of some periodontopathic bacteria in dental plaque. Copyright © 2012 Elsevier Ltd. All rights reserved.

Comparison of anti-plaque efficacy between a low and high cost dentifrice: A short term randomized double-blind trial

PubMed Central

Ganavadiya, Rahul; Shekar, B. R. Chandra; Goel, Pankaj; Hongal, Sudheer G.; Jain, Manish; Gupta, Ruchika

2014-01-01

Objective: The aim of this study was to compare the anti-plaque efficacy of a low and high cost commercially available tooth paste among 13-20 years old adolescents in a Residential Home, Bhopal, India. Materials and Methods: The study was randomized double-blind parallel clinical trial conducted in a Residential Home, Bhopal, India. A total of 65 patients with established dental plaque and gingivitis were randomly assigned to either low cost or high cost dentifrice group for 4 weeks. The plaque and gingival scores at baseline and post-intervention were assessed and compared. Statistical analysis was performed using paired t-test and the independent sample t-test. The statistical significance was fixed at 0.05. Results: Results indicated a significant reduction in plaque and gingival scores in both groups post-intervention compared with the baseline. Difference between the groups was not significant. No adverse events were reported and both the dentifrices were well-tolerated. Conclusion: Low cost dentifrice is equally effective to the high cost dentifrice in reducing plaque and gingival inflammation. PMID:25202220

Dual-mode ultrasound arrays for image-guided targeting of atheromatous plaques

NASA Astrophysics Data System (ADS)

Ballard, John R.; Casper, Andrew J.; Liu, Dalong; Haritonova, Alyona; Shehata, Islam A.; Troutman, Mitchell; Ebbini, Emad S.

2012-11-01

A feasibility study was undertaken in order to investigate alternative noninvasive treatment options for atherosclerosis. In particular, the aim of this study was to investigate the potential use of Dual-Mode Ultrasound Arrays (DMUAs) for image guided treatment of atheromatous plaques. DMUAs offer a unique treatment paradigm for image-guided surgery allowing for robust image-based identification of tissue targets for localized application of HIFU. In this study we present imaging and therapeutic results form a 3.5 MHz, 64-element fenestrated prototype DMUA for targeting lesions in the femoral artery of familial hypercholesterolemic (FH) swine. Before treatment, diagnostic ultrasound was used to verify the presence of plaque in the femoral artery of the swine. Images obtained with the DMUA and a diagnostic (HST 15-8) transducer housed in the fenestration were analyzed and used for guidance in targeting of the plaque. Discrete therapeutic shots with an estimated focal intensity of 4000-5600 W/cm2 and 500-2000 msec duration were performed at several planes in the plaque. During therapy, pulsed HIFU was interleaved with single transmit focus imaging from the DMUA and M2D imaging from the diagnostic transducer for further analysis of lesion formation. After therapy, the swine's were recovered and later sacrificed after 4 and 7 days for histological analysis of lesion formation. At sacrifice, the lower half of the swine was perfused and the femoral artery with adjoining muscle was fixed and stained with H&E to characterize HIFU-induced lesions. Histology has confirmed that localized thermal lesion formation within the plaque was achieved according to the planned lesion maps. Furthermore, the damage was confined to the plaque tissue without damage to the intima. These results offer the promise of a new treatment potentially suited for vulnerable plaques. The results also provide the first real-time demonstration of DMUA technology in targeting fine tissue structures for precise lesion formation in the presence or arterial pulsation and tissue motion. In this paper, we show results from targeting both proximal and distal sides of the vessel wall with a series of 5 - 7 discrete shots in each plane (typically three planes per plaque). Experiments to demonstrate a full treatment forming contiguous lesion within the target plaque are currently underway.

Effects of COX1-2/5-LOX blockade in Alzheimer transgenic 3xTg-AD mice.

PubMed

Bitto, Alessandra; Giuliani, Daniela; Pallio, Giovanni; Irrera, Natasha; Vandini, Eleonora; Canalini, Fabrizio; Zaffe, Davide; Ottani, Alessandra; Minutoli, Letteria; Rinaldi, Mariagrazia; Guarini, Salvatore; Squadrito, Francesco; Altavilla, Domenica

2017-05-01

Alzheimer's disease (AD) is associated with amyloid plaques (Aβ) and hyperphosphorylated tau protein tangles in the brain. We investigated the possible neuroprotective role of flavocoxid, a dual inhibitor of cyclooxygenases-1/2 (COX-1/2) and 5-Lipoxygenase (5-LOX), in triple-transgenic (3xTg-AD) mice. Mice were 3 months at the beginning of the study. Animals received once daily for 3-month saline solution or flavocoxid (20 mg/kg/ip). Morris water maze was used to assess learning and memory. Histology was performed to evidence Aβ plaques and neuronal loss, while inflammatory proteins were determined by western blot analysis. Saline-treated 3xTg-AD mice showed an impairment in spatial learning and memory (assessed at 6 months of age), and increased expression of inflammatory and apoptotic molecules. Treatment of 3xTg-AD mice with flavocoxid reduced: (1) learning and memory loss; (2) the increased eicosanoid production and the phosphorylation level of amyloid precursor protein (APP-pThr668), Aβ 1-42, p-tau (pThr181), pERK, and the activation of the NLRP3 inflammasome; (3) Aβ plaques; and (4) neuronal loss, compared to saline-treated animals. Pharmacological blockade of both COX-1/2 and 5-LOX was able to counteract the progression of AD by targeting pathophysiological mechanisms up- and downstream of Aβ and tau.

High speed intravascular photoacoustic imaging of atherosclerotic arteries (Conference Presentation)

NASA Astrophysics Data System (ADS)

Piao, Zhonglie; Ma, Teng; Qu, Yueqiao; Li, Jiawen; Yu, Mingyue; He, Youmin; Shung, K. Kirk; Zhou, Qifa; Kim, Chang-Seok; Chen, Zhongping

2016-02-01

Cardiovascular disease is the leading cause of death in the industrialized nations. Accurate quantification of both the morphology and composition of lipid-rich vulnerable atherosclerotic plaque are essential for early detection and optimal treatment in clinics. In previous works, intravascular photoacoustic (IVPA) imaging for detection of lipid-rich plaque within coronary artery walls has been demonstrated in ex vivo, but the imaging speed is still limited. In order to increase the imaging speed, a high repetition rate laser is needed. In this work, we present a high speed integrated IVPA/US imaging system with a 500 Hz optical parametric oscillator laser at 1725 nm. A miniature catheter with 1.0 mm outer diameter was designed with a 200 μm multimode fiber and an ultrasound transducer with 45 MHz center frequency. The fiber was polished at 38 degree and enclosed in a glass capillary for total internal reflection. An optical/electrical rotary junction and pull-back mechanism was applied for rotating and linearly scanning the catheter to obtain three-dimensional imaging. Atherosclerotic rabbit abdominal aorta was imaged as two frame/second at 1725 nm. Furthermore, by wide tuning range of the laser wavelength from 1680 nm to 1770 nm, spectroscopic photoacoustic analysis of lipid-mimicking phantom and an human atherosclerotic artery was performed ex vivo. The results demonstrated that the developed IVPA/US imaging system is capable for high speed intravascular imaging for plaque detection.

[Association of human epicardial adipose tissue volume and inflammatory mediators with atherosclerosis and vulnerable coronary atherosclerotic plaque].

PubMed

Zhou, Liangliang; Gong, Jianbin; Li, Demin; Lu, Guangming; Chen, Dong; Wang, Jing

2015-02-01

To investigate the relation of epicardial adipose tissue volume (EATV) determined by dual-source CT (DSCT) cardiac angiography and EAT-derived inflammatory factors to coronary heart disease (CHD) and vulnerable plaque. A total of 260 patients underwent cardiac computed tomography to evaluate stenosis of coronary artery, and blood samples were obtained from each patient. CHD was confirmed in 180 patients by DSA and CHD was excluded in the remaining 80 patients (NCHD). Vascular remodeling index and plaque vulnerability parameters (fatty volume, fibrous volume and calcification volume and fiber volume) were measured in CHD patients and correlation with EATV was analyzed. Epicardial adipose tissue (EAT) and intrathoracic adipose tissue (TAT) were collected from 40 CHD patients undergoing CABG surgery, and, mRNA and protein expressions of leptin and MMP9 were detected by RT-PCR and Western blot analysis. (1) The EATV was significantly higher in the CHD group than in NCHD group ((121.2 ± 40.6) mm³ vs. (74.7 ± 18.1) mm³, P = 0.01). (2) Subgroup analysis of the CHD patients demonstrated that EATV was significantly higher in patients with positive remodeling than in patients without positive remodeling ((97.6 ± 42.0) cm³ vs. (75.5 ± 25.4) cm³, P = 0.01). Lipid plaque volume was positively correlated with EATV (r = 0.34, P = 0.002); however, fiber plaque volume was negatively correlated with EATV (r = -0.30, P = 0.008). (3) Logistic regression analysis indicated that EATV was an independent risk factor for positive vascular remodeling (OR = 2.01, 95% CI: 1.30-2.32, P = 0.01). (4) mRNA and protein expression of leptin and MMP9 in EAT was significantly upregulated in 40 CHD patients who received CABG surgery compared to 40 NCHD patients (P < 0.01). However, there was no significant difference (P > 0.05) in mRNA and protein expression of leptin and MMP9 from the SAT between CHD and NCHD patients. (5) In the CHD group, leptin and MMP9 levels in EAT and EATV were positively correlated with lipid plaque volume and fibrous plaque volume (P < 0.05). EATV is an independent risk factors of coronary heart disease and plaque vulnerability; EAT secretion of inflammatory cytokines from CHD patients is significant increased compared to NCHD patients, EAT secretion of inflammatory cytokines are positively correlated with EATV, both of which are determinants affecting vascular remodeling. Reducing EATV might help to attenuate inflammation and plaque vulnerability and reduce the risk of coronary heart disease.

Factors associated with resistance to dementia despite high Alzheimer disease pathology.

PubMed

Erten-Lyons, D; Woltjer, R L; Dodge, H; Nixon, R; Vorobik, R; Calvert, J F; Leahy, M; Montine, T; Kaye, J

2009-01-27

Autopsy series have shown that some elderly people remain with normal cognitive function during life despite having high burdens of pathologic lesions associated with Alzheimer disease (AD) at death. Understanding why these individuals show no cognitive decline, despite high AD pathologic burdens, may be key to discovery of neuroprotective mechanisms. A total of 36 subjects who on autopsy had Braak stage V or VI and moderate or frequent neuritic plaque scores based on Consortium to Establish a Registry for Alzheimer's Disease (CERAD) standards were included. Twelve had normal cognitive function and 24 a diagnosis of AD before death. Demographic characteristics, clinical and pathologic data, as well as antemortem brain volumes were compared between the groups. In multiple regression analysis, antemortem hippocampal and total brain volumes were significantly larger in the group with normal cognitive function after adjusting for gender, age at MRI, time from MRI to death, Braak stage, CERAD neuritic plaque score, and overall presence of vascular disease. Larger brain and hippocampal volumes were associated with preserved cognitive function during life despite a high burden of Alzheimer disease (AD) pathologic lesions at death. A better understanding of processes that lead to preservation of brain volume may provide important clues for the discovery of mechanisms that protect the elderly from AD.

Statistical strategy for anisotropic adventitia modelling in IVUS.

PubMed

Gil, Debora; Hernández, Aura; Rodriguez, Oriol; Mauri, Josepa; Radeva, Petia

2006-06-01

Vessel plaque assessment by analysis of intravascular ultrasound sequences is a useful tool for cardiac disease diagnosis and intervention. Manual detection of luminal (inner) and media-adventitia (external) vessel borders is the main activity of physicians in the process of lumen narrowing (plaque) quantification. Difficult definition of vessel border descriptors, as well as, shades, artifacts, and blurred signal response due to ultrasound physical properties trouble automated adventitia segmentation. In order to efficiently approach such a complex problem, we propose blending advanced anisotropic filtering operators and statistical classification techniques into a vessel border modelling strategy. Our systematic statistical analysis shows that the reported adventitia detection achieves an accuracy in the range of interobserver variability regardless of plaque nature, vessel geometry, and incomplete vessel borders.

PLACD-7T Study: Atherosclerotic Carotid Plaque Components Correlated with Cerebral Damage at 7 Tesla Magnetic Resonance Imaging.

PubMed

den Hartog, A G; Bovens, S M; Koning, W; Hendrikse, J; Pasterkamp, G; Moll, F L; de Borst, G J

2011-02-01

In patients with carotid artery stenosis histological plaque composition is associated with plaque stability and with presenting symptomatology. Preferentially, plaque vulnerability should be taken into account in pre-operative work-up of patients with severe carotid artery stenosis. However, currently no appropriate and conclusive (non-) invasive technique to differentiate between the high and low risk carotid artery plaque in vivo is available. We propose that 7 Tesla human high resolution MRI scanning will visualize carotid plaque characteristics more precisely and will enable correlation of these specific components with cerebral damage. The aim of the PlaCD-7T study is 1: to correlate 7T imaging with carotid plaque histology (gold standard); and 2: to correlate plaque characteristics with cerebral damage ((clinically silent) cerebral (micro) infarcts or bleeds) on 7 Tesla high resolution (HR) MRI. We propose a single center prospective study for either symptomatic or asymptomatic patients with haemodynamic significant (70%) stenosis of at least one of the carotid arteries. The Athero-Express (AE) biobank histological analysis will be derived according to standard protocol. Patients included in the AE and our prospective study will undergo a pre-operative 7 Tesla HR-MRI scan of both the head and neck area. We hypothesize that the 7 Tesla MRI scanner will allow early identification of high risk carotid plaques being associated with micro infarcted cerebral areas, and will thus be able to identify patients with a high risk of periprocedural stroke, by identification of surrogate measures of increased cardiovascular risk.

PLACD-7T Study: Atherosclerotic Carotid Plaque Components Correlated with Cerebral Damage at 7 Tesla Magnetic Resonance Imaging

PubMed Central

den Hartog, A.G; Bovens, S.M; Koning, W; Hendrikse, J; Pasterkamp, G; Moll, F.L; de Borst, G.J

2011-01-01

Introduction: In patients with carotid artery stenosis histological plaque composition is associated with plaque stability and with presenting symptomatology. Preferentially, plaque vulnerability should be taken into account in pre-operative work-up of patients with severe carotid artery stenosis. However, currently no appropriate and conclusive (non-) invasive technique to differentiate between the high and low risk carotid artery plaque in vivo is available. We propose that 7 Tesla human high resolution MRI scanning will visualize carotid plaque characteristics more precisely and will enable correlation of these specific components with cerebral damage. Study objective: The aim of the PlaCD-7T study is 1: to correlate 7T imaging with carotid plaque histology (gold standard); and 2: to correlate plaque characteristics with cerebral damage ((clinically silent) cerebral (micro) infarcts or bleeds) on 7 Tesla high resolution (HR) MRI. Design: We propose a single center prospective study for either symptomatic or asymptomatic patients with haemodynamic significant (70%) stenosis of at least one of the carotid arteries. The Athero-Express (AE) biobank histological analysis will be derived according to standard protocol. Patients included in the AE and our prospective study will undergo a pre-operative 7 Tesla HR-MRI scan of both the head and neck area. Discussion: We hypothesize that the 7 Tesla MRI scanner will allow early identification of high risk carotid plaques being associated with micro infarcted cerebral areas, and will thus be able to identify patients with a high risk of periprocedural stroke, by identification of surrogate measures of increased cardiovascular risk. PMID:22294972

Plaque surface irregularity and calcification length within carotid plaque predict secondary events in patients with coronary artery disease.

PubMed

Nonin, Shinichi; Iwata, Shinichi; Sugioka, Kenichi; Fujita, Suwako; Norioka, Naoki; Ito, Asahiro; Nakagawa, Masashi; Yoshiyama, Minoru

2017-01-01

Although comprehensive risk factor modification is recommended, a uniform management strategy does not necessarily prevent secondary events in patients with coronary artery disease (CAD). Therefore, identification of high-risk patients who may benefit from more intensive interventions may improve prognosis. Carotid ultrasound can reliably identify systemic atherosclerosis, and carotid plaque and intima-media thickness (IMT) are known independent risk factors for CAD. However, it is unclear whether findings on carotid ultrasound can improve prediction of secondary CAD events. The study population comprised 146 consecutive patients with CAD (mean age, 66 ± 9 years; 126 with angina pectoris, 20 with acute myocardial infarction). IMT, plaque score, plaque area, plaque surface irregularity, and calcification length (calculated by summing the calcified lesions within each plaque accompanied by acoustic shadow) were measured at baseline. Patients were followed for 10 years to ascertain secondary CAD events defined as hard major adverse cardiovascular events (MACE; cardiac death and acute myocardial infarction) and as total MACE (hard MACE and angina pectoris with coronary revascularization). Multiple regression analysis demonstrated that calcification length (p < 0.05) and plaque surface irregularity (p < 0.01) remained independently associated with total MACE after adjustment for age, sex, diabetes mellitus, dyslipidemia, hypertension, chronic kidney disease, smoking, and multivessel CAD. These findings suggest that the combination of calcification length and plaque surface irregularity has additional value beyond traditional risk classification. Intensive intervention for these high-risk patients may avoid or delay progression of atherosclerosis towards secondary CAD events. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Magnetic resonance imaging of atherothrombotic plaques.

PubMed

Usman, Ammara; Sadat, Umar; Graves, Martin J; Gillard, Jonathan H

2015-11-01

Atherosclerosis remains the leading cause of long term morbidity and mortality worldwide, despite significant advances in its management. Vulnerable atherothrombotic plaques are predominantly responsible for thromboembolic ischaemic events in arterial beds, such as the carotid, coronary and lower limb arteries. MRI has emerged as a non-invasive, non-irradiating and highly reproducible imaging technique which allows detailed morphological and functional assessment of such plaques. It also has the potential to monitor the efficacy of established and evolving anti-atherosclerosis drugs. It is envisaged that by careful identification and understanding of the underlying cellular and molecular mechanisms that govern atherosclerosis, novel treatment strategies can be formulated which may reduce the persistent high mortality and morbidity rates associated with this disease. MRI shows promise in achieving this goal. Copyright © 2015 Elsevier Ltd. All rights reserved.

Community and gene composition of a human dental plaque microbiota obtained by metagenomic sequencing

PubMed Central

Xie, G.; Chain, P.S.G.; Lo, C.; Liu, K-L.; Gans, J.; Merritt, J.; Qi, F.

2010-01-01

SUMMARY Human dental plaque is a complex microbial community containing an estimated 700 to 19,000 species/phylotypes. Despite numerous studies analysing species richness in healthy and diseased human subjects, the true genomic composition of the human dental plaque microbiota remains unknown. Here we report a metagenomic analysis of a healthy human plaque sample using a combination of second-generation sequencing platforms. A total of 860 million base pairs of non-human sequences were generated. Various analysis tools revealed the presence of 12 well-characterized phyla, members of the TM-7 and BRC1 clade, and sequences that could not be classified. Both pathogens and opportunistic pathogens were identified, supporting the ecological plaque hypothesis for oral diseases. Mapping the metagenomic reads to sequenced reference genomes demonstrated that 4% of the reads could be assigned to the sequenced species. Preliminary annotation identified genes belonging to all known functional categories. Interestingly, although 73% of the total assembled contig sequences were predicted to code for proteins, only 51% of them could be assigned a functional role. Furthermore, ~ 2.8% of the total predicted genes coded for proteins involved in resistance to antibiotics and toxic compounds, suggesting that the oral cavity is an important reservoir for antimicrobial resistance. PMID:21040513

Community and gene composition of a human dental plaque microbiota obtained by metagenomic sequencing.

PubMed

Xie, G; Chain, P S G; Lo, C-C; Liu, K-L; Gans, J; Merritt, J; Qi, F

2010-12-01

Human dental plaque is a complex microbial community containing an estimated 700 to 19,000 species/phylotypes. Despite numerous studies analysing species richness in healthy and diseased human subjects, the true genomic composition of the human dental plaque microbiota remains unknown. Here we report a metagenomic analysis of a healthy human plaque sample using a combination of second-generation sequencing platforms. A total of 860 million base pairs of non-human sequences were generated. Various analysis tools revealed the presence of 12 well-characterized phyla, members of the TM-7 and BRC1 clade, and sequences that could not be classified. Both pathogens and opportunistic pathogens were identified, supporting the ecological plaque hypothesis for oral diseases. Mapping the metagenomic reads to sequenced reference genomes demonstrated that 4% of the reads could be assigned to the sequenced species. Preliminary annotation identified genes belonging to all known functional categories. Interestingly, although 73% of the total assembled contig sequences were predicted to code for proteins, only 51% of them could be assigned a functional role. Furthermore, ~2.8% of the total predicted genes coded for proteins involved in resistance to antibiotics and toxic compounds, suggesting that the oral cavity is an important reservoir for antimicrobial resistance. © 2010 John Wiley & Sons A/S.

Outcomes and Control Rates for I-125 Plaque Brachytherapy for Uveal Melanoma: A Community-Based Institutional Experience

PubMed Central

Cook, Taylor

2014-01-01

Purpose. To evaluate our community-based institutional experience with plaque brachytherapy for uveal melanomas with a focus on local control rates, factors impacting disease progression, and dosimetric parameters impacting treatment toxicity. Methods and Materials. Our institution was retrospectively reviewed from 1996 to 2011; all patients who underwent plaque brachytherapy for uveal melanoma were included. Follow-up data were collected regarding local control, distant metastases, and side effects from treatment. Analysis was performed on factors impacting treatment outcomes and treatment toxicity. Results. A total of 107 patients underwent plaque brachytherapy, of which 88 had follow-up data available. Local control at 10 years was 94%. Freedom from progression (FFP) and overall survival at 10 years were 83% and 79%, respectively. On univariate analysis, there were no tumor or dosimetric treatment characteristics that were found to have a prognostic impact on FFP. Brachytherapy treatment was well tolerated, with clinically useful vision (>20/200) maintained in 64% of patients. Statistically significant dosimetric relationships were established with cataract, glaucoma, and retinopathy development (greatest P = 0.05). Conclusions. Treatment with plaque brachytherapy demonstrates excellent outcomes in a community-based setting. It is well tolerated and should remain a standard of care for COMS medium sized tumors. PMID:24734198

Intra-familial comparison of supragingival dental plaque microflora using the checkerboard DNA-DNA hybridisation technique.

PubMed

Mannaa, Alaa; Carlén, Anette; Dahlén, Gunnar; Lingström, Peter

2012-12-01

The aims of the present study were to correlate the quantified supragingival plaque bacteria between mothers and their children and identify possible microbial associations. A total of 86 mothers and their 4- to 6-year-old and 12- to 16-year-old children participated. Pooled supragingival plaque samples were obtained from interproximal sites between teeth 16/15, 25/26, 35/36 and 46/45 in mothers and older children and teeth 55/54, 64/65, 74/75 and 85/84 in younger children. All the samples were individually analysed for their content of 18 bacterial strains using checkerboard DNA-DNA hybridisation (whole genomic probes). Microbial associations were sought using cluster analysis (dendrogram) for all three age groups together, while community ordination techniques were used for each of the three groups separately. Three complexes were formed from the dendrogram in addition to associations between these complexes and remaining bacterial strains. Principal component analysis results were similar in all three groups. The correlation analyses of bacterial counts between mothers and their children showed a significant association for most of the bacterial strains (p<0.05 or 0.01). Supragingival plaque microbiota are correlated between mothers and their children. In addition, similar supragingival plaque microbial associations are present in family members.. Copyright © 2012 Elsevier Ltd. All rights reserved.

The Clinical Effectiveness of Post-Brushing Rinsing in Reducing Plaque and Gingivitis: A Systematic Review

PubMed Central

Patthi, Basavaraj; Singla, Ashish; Gupta, Ritu; Jankiram, Chandrasheker; Kumar, Jishnu Krishna; Vashishtha, Vaibhav; Malhi, Ravneet

2016-01-01

Introduction Dental plaque is the major etiological factor associated with the development of gingivitis. Hence, maintenance of oral hygiene is very essential. Aim To systematically review the literature on the effects of a post toothbrushing rinsing on plaque and parameters of gingival inflammation. Materials and Methods A literature review was performed in PubMed Central and Cochrane library, embase, google scholar were searched up to February 2015 to identify appropriate studies. The primary outcome measure was plaque and gingival inflammation reduction. Results Out of the total 56 titles appeared, 08articles fulfilled the criteria and were selected for the review. One article which was hand searched and one article which was through e-mail was included. A statistically significant reduction in overall plaque and gingivitis was noted when different mouth rinses were compared to the control (p<0.05). It was seen that chlorhexidine is the best antiplaque and antigingivitis agent but due to its side effects after continuous use, was not indicated for long term use. Probiotic was superior to chlorhexidine in terms of reduction of gingival inflammation. Conclusion There are relatively few studies evaluating the association between post toothbrushing rinsing and gingivitis. A clear effect was observed, indicating that different mouthrinses (chlorhexidine, probiotic, herbal, essential oil mouthrinse) when used as an adjunct to mechanical means of oral hygiene, provides an additional benefit with regard to plaque and gingivitis reduction as compared to a placebo or control. PMID:27437376

Clinical and microbiological benefits of strict supragingival plaque control as part of the active phase of periodontal therapy.

PubMed

Feres, Magda; Gursky, Lauren Christine; Faveri, Marcelo; Tsuzuki, Claudia Ota; Figueiredo, Luciene Cristina

2009-10-01

To compare the clinical and microbiological effects of scaling and root planing (SRP) alone or combined with mechanical [professional plaque control (PPC)] or chemical [chlorhexidine rinsing (CHX)] control of supragingival plaque in the treatment of chronic periodontitis. Sixty subjects were randomly assigned to receive SRP alone or combined with PPC (twice a week) or with CHX rinsing (twice a day). The adjunctive treatments began with SRP and were continued for 42 days. Clinical and microbiological examinations were performed at baseline, 2 and 6 months post-therapy. Subgingival plaque samples were analysed for 38 bacterial species by checkerboard DNA-DNA hybridization. The two test treatments were more effective in improving probing depth and clinical attachment level (CAL) than SRP alone, even in intermediate and deep sites. CAL gain was better maintained in the CHX group. The most beneficial microbiological changes were observed in CHX-treated subjects, who showed a significant reduction in the proportions of red and orange complexes, as well as an increase in the proportions of the host-compatible bacterial species. Strict plaque control performed during and after SRP improves periodontal treatment outcomes. The greatest microbiological and clinical benefits were observed with the use of CHX rinsing.

Mechanism of Enhancement of Virus Plaques by Cationic Polymers

PubMed Central

Wallis, Craig; Melnick, Joseph L.

1968-01-01

It has been assumed that plaque enhancement by cationic polymers is due to their binding of sulfated polysaccharides in agar. However, viruses that are enhanced by cationic polymers, diethylaminoethyl-dextran, and protamine were found not to be inhibited by polyanions in agar under the usual overlay conditions. In the case of adenovirus, enhancement by protamine seems to be due to the protamine serving as a source of arginine; enzymes released from the cultured cells digest the protamine and provide a reservoir of arginine for the cells. Other viruses (herpes and echovirus types 3, 4, 5, and 6) known to be susceptible to agar inhibitors were found to be enhanced by cationic polymers even under starch gel and methylcellulose overlays, which are free of polyanions. Since cationic polymers enhance the diffusion of virus through agar or starch gel, plaque enhancement seems to be the result of the gel becoming positively charged so that viruses can move effectively through them. The observation that starch gel and methylcellulose enhance plaque formation with viruses known to be inhibited under agar was also reinvestigated. When the consistency of the agar gel was reduced to the same viscosity of starch gel and methylcellulose overlays, the same plaque counts and sizes were observed under all three overlays. PMID:4986901

Molecular Imaging of Inflammation in Atherosclerosis

PubMed Central

Wildgruber, Moritz; Swirski, Filip K.; Zernecke, Alma

2013-01-01

Acute rupture of vulnerable plaques frequently leads to myocardial infarction and stroke. Within the last decades, several cellular and molecular players have been identified that promote atherosclerotic lesion formation, maturation and plaque rupture. It is now widely recognized that inflammation of the vessel wall and distinct leukocyte subsets are involved throughout all phases of atherosclerotic lesion development. The mechanisms that render a stable plaque unstable and prone to rupture, however, remain unknown and the identification of the vulnerable plaque remains a major challenge in cardiovascular medicine. Imaging technologies used in the clinic offer minimal information about the underlying biology and potential risk for rupture. New imaging technologies are therefore being developed, and in the preclinical setting have enabled new and dynamic insights into the vessel wall for a better understanding of this complex disease. Molecular imaging has the potential to track biological processes, such as the activity of cellular and molecular biomarkers in vivo and over time. Similarly, novel imaging technologies specifically detect effects of therapies that aim to stabilize vulnerable plaques and silence vascular inflammation. Here we will review the potential of established and new molecular imaging technologies in the setting of atherosclerosis, and discuss the cumbersome steps required for translating molecular imaging approaches into the clinic. PMID:24312156

Infection of nonphagocytic host cells by legionella.

PubMed

Day, Shandra R; Sifri, Costi D; Hoffman, Paul S

2013-01-01

Legionella pneumophila is an intracellular pathogen of free-living protozoa that can also infect alveolar macrophages, L929 fibroblast cells, and HeLa cells. Infection of nonphagocytic cells by L. pneumophila can be used to study invasion mechanisms, compare infectivity of different strains and identify factors important for virulence. Virulent strains of L. pneumophila exposed to monolayers of L929 cells are able to invade and form virus-like plaques, which can be enumerated as a measure of infectivity. Invasiveness of HeLa cells can also be used to evaluate relative infectivity and to study mechanisms of invasion and to track the development of cyst-like forms. The detailed methods of both the L929 plaque assay and HeLa cell invasion assay are described.

Gene profiling of cathepsin K deficiency in atherogenesis: profibrotic but lipogenic.

PubMed

Lutgens, S P M; Kisters, N; Lutgens, E; van Haaften, R I M; Evelo, C T A; de Winther, M P J; Saftig, P; Daemen, M J A P; Heeneman, S; Cleutjens, K B J M

2006-11-01

Recently, we showed that cathepsin K deficiency reduces atherosclerotic plaque progression, induces plaque fibrosis, but aggravates macrophage foam cell formation in the ApoE -/- mouse. To obtain more insight into the molecular mechanisms by which cathepsin K disruption evokes the observed phenotypic changes, we used microarray analysis for gene expression profiling of aortic arches of CatK -/-/ApoE -/- and ApoE -/- mice on a mouse oligo microarray. Out of 20 280 reporters, 444 were significantly differentially expressed (p-value of < 0.05, fold change of > or = 1.4 or < or = - 1.4, and intensity value of > 2.5 times background in at least one channel). Ingenuity Pathway Analysis and GenMAPP revealed upregulation of genes involved in lipid uptake, trafficking, and intracellular storage, including caveolin - 1, - 2, - 3 and CD36, and profibrotic genes involved in transforming growth factor beta (TGFbeta) signalling, including TGFbeta2, latent TGFbeta binding protein-1 (LTBP1), and secreted protein, acidic and rich in cysteine (SPARC), in CatK -/-/ApoE -/- mice. Differential gene expression was confirmed at the mRNA and protein levels. In vitro modified low density lipoprotein (LDL) uptake assays, using bone marrow derived macrophages preincubated with caveolae and scavenger receptor inhibitors, confirmed the importance of caveolins and CD36 in increasing modified LDL uptake in the absence of cathepsin K. In conclusion, we suggest that cathepsin K deficiency alters plaque phenotype not only by decreasing proteolytic activity, but also by stimulating TGFbeta signalling. Besides this profibrotic effect, cathepsin K deficiency has a lipogenic effect owing to increased lipid uptake mediated by CD36 and caveolins. Copyright 2006 Pathological Society of Great Britain and Ireland.

Inhibition of Bim Enhances Replication of Varicella-Zoster Virus and Delays Plaque Formation in Virus-Infected Cells

PubMed Central

Liu, XueQiao

2014-01-01

Programmed cell death (apoptosis) is an important host defense mechanism against intracellular pathogens, such as viruses. Accordingly, viruses have evolved multiple mechanisms to modulate apoptosis to enhance replication. Varicella-zoster virus (VZV) induces apoptosis in human fibroblasts and melanoma cells. We found that VZV triggered the phosphorylation of the proapoptotic proteins Bim and BAD but had little or no effect on other Bcl-2 family members. Since phosphorylation of Bim and BAD reduces their proapoptotic activity, this may prevent or delay apoptosis in VZV-infected cells. Phosphorylation of Bim but not BAD in VZV-infected cells was dependent on activation of the MEK/extracellular signal-regulated kinase (ERK) pathway. Cells knocked down for Bim showed delayed VZV plaque formation, resulting in longer survival of VZV-infected cells and increased replication of virus, compared with wild-type cells infected with virus. Conversely, overexpression of Bim resulted in earlier plaque formation, smaller plaques, reduced virus replication, and increased caspase 3 activity. Inhibition of caspase activity in VZV-infected cells overexpressing Bim restored levels of virus production similar to those seen with virus-infected wild-type cells. Previously we showed that VZV ORF12 activates ERK and inhibits apoptosis in virus-infected cells. Here we found that VZV ORF12 contributes to Bim and BAD phosphorylation. In summary, VZV triggers Bim phosphorylation; reduction of Bim levels results in longer survival of VZV-infected cells and increased VZV replication. PMID:24227856

Biologic plausibility, cellular effects, and molecular mechanisms of eicosapentaenoic acid (EPA) in atherosclerosis.

PubMed

Borow, Kenneth M; Nelson, John R; Mason, R Preston

2015-09-01

Residual cardiovascular (CV) risk remains in dyslipidemic patients despite intensive statin therapy, underscoring the need for additional intervention. Eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid, is incorporated into membrane phospholipids and atherosclerotic plaques and exerts beneficial effects on the pathophysiologic cascade from onset of plaque formation through rupture. Specific salutary actions have been reported relating to endothelial function, oxidative stress, foam cell formation, inflammation, plaque formation/progression, platelet aggregation, thrombus formation, and plaque rupture. EPA also improves atherogenic dyslipidemia characterized by reduction of triglycerides without raising low-density lipoprotein cholesterol. Other beneficial effects of EPA include vasodilation, resulting in blood pressure reductions, as well as improved membrane fluidity. EPA's effects are at least additive to those of statins when given as adjunctive therapy. In this review, we present data supporting the biologic plausibility of EPA as an anti-atherosclerotic agent with potential clinical benefit for prevention of CV events, as well as its cellular effects and molecular mechanisms of action. REDUCE-IT is an ongoing, randomized, controlled study evaluating whether the high-purity ethyl ester of EPA (icosapent ethyl) at 4 g/day combined with statin therapy is superior to statin therapy alone for reducing CV events in high-risk patients with mixed dyslipidemia. The results from this study are expected to clarify the role of EPA as adjunctive therapy to a statin for reduction of residual CV risk. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Clinical outcome of nonculprit plaque ruptures in patients with acute coronary syndrome in the PROSPECT study.

PubMed

Xie, Yong; Mintz, Gary S; Yang, Junqing; Doi, Hiroshi; Iñiguez, Andrés; Dangas, George D; Serruys, Patrick W; McPherson, John A; Wennerblom, Bertil; Xu, Ke; Weisz, Giora; Stone, Gregg W; Maehara, Akiko

2014-04-01

The aim of this study was to report the frequency, patient and lesion-related characteristics, and outcomes of subclinical, nonculprit plaque ruptures in the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study. Plaque rupture and subsequent thrombosis is the most common cause of acute coronary syndrome (ACS). Secondary, subclinical, nonculprit plaque ruptures have been seen in both stable patients and patients with ACS; however, reports of the natural history of these secondary plaque ruptures are limited. After successful stenting in 697 patients with ACS, 3-vessel grayscale and intravascular ultrasound virtual histology (IVUS-VH) was performed in the proximal-mid segments of all 3 coronary arteries as part of a prospective multicenter study. Among 660 patients with complete IVUS data, 128 plaque ruptures were identified in 105 nonculprit lesions in 100 arteries from 93 patients (14.1%). Although the minimum lumen area (MLA) was similar, the plaque burden was significantly greater in nonculprit lesions with a plaque rupture compared with nonculprit lesions without a plaque rupture (66.0% [95% confidence interval: 64.5% to 67.4%] vs. 56.0% [95% confidence interval: 55.6% to 56.4%]; p < 0.0001). IVUS-VH analysis revealed that a nonculprit lesion with a plaque rupture was more often classified as a fibroatheroma than a nonculprit lesion without a plaque rupture (77.1% vs. 51.4%; p < 0.0001). Independent predictors of a plaque rupture were lesion length (per 10 mm; odds ratio: 1.30; p < 0.0001), plaque burden at the MLA site (per 10%; odds ratio: 2.56; p < 0.0001), vessel area at the MLA site (per 1 mm(2); odds ratio: 1.13; p < 0.0001), and VH-thin-cap fibroatheroma (odds ratio: 1.80; p = 0.016). During 3 years of follow-up, the incidence of overall major adverse cardiac events did not differ significantly between the patients with and patients without subclinical, nonculprit plaque ruptures. Secondary, nonculprit plaque ruptures were seen in 14% of patients with ACS and were associated with a fibroatheroma phenotype with a residual necrotic core but not with adverse outcomes if patients were treated with optimal medical therapy as part of a multicenter study. (Providing Regional Observations to Study Predictors of Events in the Coronary Tree [PROSPECT]; NCT00180466). Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

In Idiopathic Calcium Oxalate Stone Formers, Unattached Stones Show Evidence of Having Originated as Attached Stones on Randall’s Plaque

PubMed Central

Miller, Nicole L.; Williams, James C.; Evan, Andrew P.; Bledsoe, Sharon B.; Coe, Fredric L.; Worcester, Elaine M.; Munch, Larry C.; Handa, Shelly E.; Lingeman, James E.

2009-01-01

Objective To analyze the structure and composition of unattached stones in idiopathic calcium oxalate stone formers (ICSF) and compare them to attached stones from the same cohort in order to investigate whether more than one pathogenic mechanism exists for stone formation in ICSF. Patients and methods ICSF undergoing percutaneous nephrolithotomy or ureteroscopy for treatment of nephrolithiasis were consented for this study. All accessible renal papillae were endoscopically imaged using a digital endoscope. All stones were removed and determined by the operating surgeon to be attached or unattached to the underlying papilla. Micro-computed tomography (micro-CT), which provides three-dimensional analysis of entire stones, was used to compare the structure and composition of attached versus unattached stones. Results Of 115 stones collected from 9 patients (12 renal units), only 25 stones were found not to be attached to renal papillae. Of these 25 stones, 4 were lost and 12 showed definite morphological evidence of having been attached to tissue, probably having been knocked off of papillae during access. For the remaining 9 stones, micro-CT analysis revealed at least one internal region of calcium phosphate within each of these unattached calcium oxalate (CaOx) stones. That is, the internal structure of the unattached stones is consistent with their having originated attached to RP, and then having become detached but retained in the kidney, with new layers of CaOx eventually covering the original attachment site. Conclusions Micro CT analysis supports the hypothesis that in ICSF, both attached and unattached stones occur as a result of a common pathogenic mechanism. That is, in this type of stone former, CaOx stones—even those not showing morphology that betrays attachment—all originate attached to interstitial plaque on the renal papilla. PMID:19549258

A quantitative comparison of plaque types in Alzheimer's disease and senile dementia of the Lewy body type.

PubMed

McKenzie, J E; Edwards, R J; Gentleman, S M; Ince, P G; Perry, R H; Royston, M C; Roberts, G W

1996-01-01

In a previous study we reported no difference in the overall beta-amyloid protein (beta AP) load between Alzheimer's disease (AD) and senile dementia of the Lewy body type (SDLT). However, it is possible that differences in the morphology of beta AP plaque types exist, analogous to the differences in cytoskeletal pathology found in these two disorders. We have carried out a quantitative image analysis of plaque subtypes in the temporal lobe of AD (n = 8), SDLT (n = 9) and control (n = 11) cases. Measurements of beta AP load and plaque density were consistently higher in AD and SDLT than in controls. When AD and SDLT cases were compared no differences were seen in either the density or relative proportions of classic and diffuse plaques. Based on these results we suggest that the variation in the clinical course of these diseases reflects differences in the cytoskeletal pathology, whereas the final stages of profound dementia common to both disorders is associated with the deposition of beta AP.

Prothrombotic changes in diabetes mellitus.

PubMed

Morel, Olivier; Jesel, Laurence; Abbas, Malak; Morel, Nicolas

2013-07-01

Although our understanding of vascular pathology has greatly improved in recent years, the cellular and molecular mechanisms underlying the enhanced thrombotic propensity in type 2 diabetes mellitus (T2DM) remain incompletely characterized. Detrimental interactions between activated vascular cells (i.e., platelets, leukocytes, endothelial cells) and the vulnerable atheromatous plaque are a major determinant of the increased atherothrombotic burden in T2DM patients. Endothelial damage and accelerated senescence, impairment of the endothelial progenitor cell repair system, plaque neovascularization and inflammation, decreased clearance of detrimental molecules within the plaque, and increased expression of matrix metalloproteinases may collectively contribute to intraplaque hemorrhage and subsequent rupture. Notably, recent data demonstrates the central importance of the tissue factor-microparticle-mediated pathway in diabetic thrombophilia and cardiovascular complications. Acting as detrimental amplifiers of various biological responses (including thrombogenicity and plaque remodeling), microparticles have also emerged as a key marker of global vascular damage in T2DM patients. Available evidence suggests that targeting the tissue factor-microparticle pathway may be a promising approach for reducing the burden of the atherosclerotic complications of diabetes. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Myocardial Bridge and Acute Plaque Rupture.

PubMed

Perl, Leor; Daniels, David; Schwartz, Jonathan; Tanaka, Shige; Yeung, Alan; Tremmel, Jennifer A; Schnittger, Ingela

2016-01-01

A myocardial bridge (MB) is a common anatomic variant, most frequently located in the left anterior descending coronary artery, where a portion of the coronary artery is covered by myocardium. Importantly, MBs are known to result in a proximal atherosclerotic lesion. It has recently been postulated that these lesions predispose patients to acute coronary events, even in cases of otherwise low-risk patients. One such mechanism may involve acute plaque rupture. In this article, we report 2 cases of patients with MBs who presented with acute coronary syndromes despite having low cardiovascular risk. Their presentation was life-risking and both were treated urgently and studied with coronary angiographies and intravascular ultrasound. This latter modality confirmed a rupture of an atherosclerotic plaque proximal to the MB as a likely cause of the acute events. These cases, of unexplained acute coronary syndrome in low-risk patients, raise the question of alternative processes leading to the event and the role MB play as an underlying cause of ruptured plaques. In some cases, an active investigation for this entity may be warranted, due to the prognostic implications of the different therapeutic modalities, should an MB be discovered.

Sinter of uniform, predictable, blemish-free nickel plaque for large aerospace nickel cadmium cells

NASA Technical Reports Server (NTRS)

Seiger, H. N.

1975-01-01

A series of nickel slurry compositions were tested. Important slurry parameters were found to be the nature of the binder, a pore former and the method of mixing. A slow roll mixing which is non-turbulent successfully eliminated entrapped air so that bubbles and pockets were avoided in the sinter. A slurry applicator was developed which enabled an equal quantity of slurry to be applied to both sides of the grid. Sintering in a furnace having a graded atmosphere characteristic, ranging from oxidizing to strongly reducing, improved adhesion of porous sinter to grid and resulted in a uniform welding of nickel particles to each other throughout the plaque. Sintering was carried out in a horizontal furnace having three heating zones and 16 heating control circuits. Tests used for plaque evaluation include (1) appearance, (2) grid location and adhesion, (3) mechanical strength, (4) thickness, (5) weight per unit area, (6) void volume per unit area, (7) surface area and (8) electrical resistance. Plaque material was impregnated using Heliotek proprietary processes and 100 AH cells were fabricated.

Bacterial sex in dental plaque.

PubMed

Olsen, Ingar; Tribble, Gena D; Fiehn, Nils-Erik; Wang, Bing-Yan

2013-01-01

Genes are transferred between bacteria in dental plaque by transduction, conjugation, and transformation. Membrane vesicles can also provide a mechanism for horizontal gene transfer. DNA transfer is considered bacterial sex, but the transfer is not parallel to processes that we associate with sex in higher organisms. Several examples of bacterial gene transfer in the oral cavity are given in this review. How frequently this occurs in dental plaque is not clear, but evidence suggests that it affects a number of the major genera present. It has been estimated that new sequences in genomes established through horizontal gene transfer can constitute up to 30% of bacterial genomes. Gene transfer can be both inter- and intrageneric, and it can also affect transient organisms. The transferred DNA can be integrated or recombined in the recipient's chromosome or remain as an extrachromosomal inheritable element. This can make dental plaque a reservoir for antimicrobial resistance genes. The ability to transfer DNA is important for bacteria, making them better adapted to the harsh environment of the human mouth, and promoting their survival, virulence, and pathogenicity.

The Association of Pericardial Fat with Coronary Artery Plaque Index at MR Imaging: The Multi-Ethnic Study of Atherosclerosis (MESA)

PubMed Central

Miao, Cuilian; Chen, Shaoguang; Ding, Jingzhong; Liu, Kiang; Li, Debiao; Macedo, Robson; Lai, Shenghan; Vogel-Claussen, Jens; Brown, Elizabeth R.; Lima, João A. C.

2011-01-01

Purpose: To determine the relationship of pericardial fat, which secretes proinflammatory markers that have been implicated in coronary atherosclerosis, with atherosclerotic plaque in an asymptomatic population–based cohort. Materials and Methods: In this institutional review board–approved study, all participants supplied written informed consent. One hundred eighty-three participants (89 women, 94 men; mean age, 61 years ± 9 [standard deviation]) from the community-based Multi-Ethnic Study of Atherosclerosis (MESA) were included. The coronary artery eccentricity (ratio of maximal to minimal coronary artery wall thickness) was determined by using magnetic resonance (MR) imaging and served as an index of plaque burden. The pericardial fat volume was determined by using computed tomography. Linear regression coefficient analysis was used to correlate pericardial fat volume with coronary artery wall thickness and plaque eccentricity. Results: Pericardial fat volume correlated significantly with degree of plaque eccentricity (P < .05) in both men and women. After adjustments for body mass index (BMI) and waist circumference, traditional risk factors, C-reactive protein level, and coronary artery calcium content, the relationship between pericardial fat and plaque eccentricity remained significant in men (P < .01) but not in women. BMI and waist circumference correlated with degree of plaque eccentricity in the univariate model (P < .05) but not after adjustment for pericardial fat volume or traditional risk factors. Conclusion: Pericardial fat volume, rather than BMI and waist circumference, was more strongly related to plaque eccentricity as a measure of coronary atherosclerotic plaque burden. The results support the proposed role of pericardial fat in association with atherosclerosis. © RSNA, 2011 PMID:21846753

The effect of iron plaque on uptake and translocation of norfloxacin in rice seedlings grown in paddy soil.

PubMed

Yan, Dafang; Ma, Wei; Song, Xiaojing; Bao, Yanyu

2017-03-01

Although the role of iron plaque on rice root surface has been investigated in recent years, its effect on antibiotic uptake remains uncertain. In the study, pot experiment was conducted to investigate the effect of iron plaque on uptake and translocation of norfloxacin (adding 10 and 50 mg·kg -1 treatments) in rice seedlings grown in paddy soil. Iron plaque was induced by adding different amounts of Fe(II) in soil. The results showed that the presence of norfloxacin can decrease the amount of iron plaque induced. After rice with iron plaque induced, norfloxacin was mainly accumulated in iron plaque on root surface, followed by inside root, but its translocation from root to other rice tissues is not observed. Iron plaque played the role of a barrier for norfloxacin uptake into rice roots under high norfloxacin concentration of 50 mg·kg -1 , however not that under low concentration of 10 mg·kg -1 . And the barrier function was the most strongest with adding Fe(II) of 30 mg·kg -1 as combined action of iron plaque and rhizosphere effect. Fluorescence microscope analysis showed that norfloxacin mainly distributed in the outside of root cell, which showed its translocation as apoplastic pathway in rice. Comparing with non-rhizosphere, more norfloxacin was accumulated in rhizosphere soil. Maybe, strong root oxidization (high Eh values) induced more iron oxide formation in rhizosphere and on root surface, which led to norfloxacin's mobility towards to rhizosphere through its strong adsorption of iron oxides and then promoted its uptake by rice on root surface.

Gender differences in coronary plaque composition by coronary computed tomography angiography.

PubMed

Blaha, Michael J; Nasir, Khurram; Rivera, Juan J; Choi, Eue-Keun; Chang, Sung-A; Yoon, Yeonyee E; Chun, Eun Ju; Choi, Sang-il; Agatston, Arthur; Blumenthal, Roger S; Chang, Hyuk-Jae

2009-12-01

Coronary computed tomography angiography allows the differentiation of non-calcified (NCAP), calcified (CAP), and mixed coronary artery plaques (MCAP). Although males are thought to have a higher prevalence of atherosclerosis for a given age, there are currently few data regarding age-adjusted sex differences in plaque morphology and composition. We studied 1015 consecutive asymptomatic South Korean patients (49+/-10 years, 64% men) who underwent 64-slice coronary computed tomography angiography during a routine health evaluation. Coronary plaque characteristics were analyzed on a per-segment basis according to the modified AHA classification. Plaques with more than 50% calcified tissue were classified as CAP, plaques with less than 50% calcified tissue were classified as MCAP, and plaques without calcium were classified as NCAP. Multiple regression analysis was used to describe the cross-sectional association between sex and plaque-type burden (>or=2 affected segments) after adjustment for age and other cardiovascular risk factors. There was a greater prevalence of coronary plaque among men (13 vs. 4%, P<0.001). Males were more likely to have an increased burden of CAP (4 vs. 1%, P = 0.01) and MCAP (5 vs. 1%, P<0.001), whereas the burden of NCAP was similar across sex (2 vs. 1%, P = 0.28). After multivariable adjustment, men have six to seven times greater odds of having an increased burden of CAP and MCAP, whereas no sex difference was observed in the burden of NCAP. In this population of asymptomatic middle-aged Korean individuals, males had a significantly greater burden of MCAP and CAP. Future studies will determine whether these differences contribute to the accelerated cardiovascular risk observed in men.

Association between triglyceride/HDL cholesterol ratio and carotid atherosclerosis in postmenopausal middle-aged women.

PubMed

Masson, Walter; Siniawski, Daniel; Lobo, Martín; Molinero, Graciela; Huerín, Melina

2016-01-01

The triglyceride/HDL cholesterol ratio, as a surrogate marker of insulin resistance, may be associated to presence of subclinical carotid atherosclerosis in postmenopausal women. The aim of this study was to explore this association. Women (last menstrual period≥2 years) in primary prevention up to 65 years of age were recruited. Association between the triglyceride/HDL cholesterol (HDL-C) ratio and presence of carotid plaque, assessed by ultrasonography, was analyzed. ROC analysis was performed, determining the precision of this ratio to detect carotid plaque. A total of 332 women (age 57±5 years) were recruited. Triglyceride/HDL-C ratio was 2.35±1.6. Prevalence of carotid plaque was 29%. Women with carotid plaque had higher triglyceride/HDL-C ratios (3.33±1.96 vs. 2.1±1.2, P<.001) than women with no carotid plaque. A positive relationship was seen between quintiles of this ratio and prevalence of carotid plaque (p<.001). Regardless of other risk factors, women with higher triglyceride/HDL-C ratios were more likely to have carotid plaque (odds ratio 1.47, 95% confidence interval 1.20-1.79, P<.001). The area under the curve of the triglyceride/HDL-C ratio to detect carotid plaque was .71 (95% confidence interval .65 to .76), and the optimal cut-off point was 2.04. In postmenopausal women in primary prevention, insulin resistance, estimated from the triglyceride/HDL-C ratio, was independently associated to a greater probability of carotid plaque. A value of such ratio greater than 2 may be used for assessing cardiovascular risk in this particular group of women. Copyright © 2016 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

The use of plaque score measurements to assess changes in atherosclerotic plaque burden induced by lipid-lowering therapy over time: the METEOR study.

PubMed

Peters, Sanne A E; Dogan, Soner; Meijer, Rudy; Palmer, Mike K; Grobbee, Diederick E; Crouse, John R; O'Leary, Daniel H; Evans, Gregory W; Raichlen, Joel S; Bots, Michiel L

2011-01-01

To evaluate whether plaque scoring measurements are able to track changes in atherosclerotic plaque burden over time and to study whether this is affected by lipid-lowering therapy. Data used were from METEOR (Measuring Effects on Intima-Media Thickness: an Evaluation Of Rosuvastatin), a randomized controlled trial of rosuvastatin 40 mg among 984 low-risk patients with modest carotid intima-media thickening (CIMT). In this analysis, duplicate ultrasound images from 12 carotid sites were collected at the baseline and end of the study from 495 European patients and were evaluated for plaque presence and severity. Plaques were scored from near and far walls of the 12 sites (0= none; 1= minimal; 2= moderate; 3= severe) and plaque scores (PS) were combined into two summary measures for each examination. The MeanMaxPS is the mean over the 12 carotid sites of the maximum score at each site and the MaxMaxPS reflects the most severe lesion at any site. Baseline MeanMaxPS and MaxMaxPS were 0.31 (SD: 0.20) and 1.15 (SD: 0.51), respectively. Changes in MeanMaxPS and MaxMaxPS significantly differed between rosuvastatin and placebo (mean difference: -0.03 [SE: 0.01; p =0.016] and -0.09 [SE: 0.04; p =0.027], respectively). In contrast to rosuvastatin, which demonstrated no change from the baseline, placebo showed significant progression in MeanMaxPS and MaxMaxPS (p =0.002; both). The plaque-scoring method proved capable of assessing the change in atherosclerotic plaque burden over time and proved useful to evaluate lipid-lowering in asymptomatic individuals with a low risk of cardiovascular disease and subclinical atherosclerosis.

Is the red fluorescence of dental plaque related to its cariogenicity?

NASA Astrophysics Data System (ADS)

Bittar, Daniela G.; Pontes, Laura Regina A.; Calvo, Ana Flávia B.; Novaes, Tatiane F.; Braga, Mariana M.; Freitas, Patrícia M.; Tabchoury, Cinthia P. M.; Mendes, Fausto M.

2014-06-01

It has been speculated that the red fluorescence emitted by dental plaque could be related to its cariogenicity. To test this hypothesis, we designed this crossover in situ study, with two experimental phases of 14 days each. Seventeen volunteers, wearing a palatal appliance with bovine enamel blocks, were instructed to drip a 20% sucrose solution (experimental group) or purified water (control group) onto the enamel blocks eight times daily. The specimens were removed after 4, 7, 10, and 14 days, and the red fluorescence of dental plaque formed on the enamel blocks was assessed using a quantitative light-induced fluorescence device. After the plaque removal, surface and cross-sectional microhardness tests were performed to assess the mineral loss. The comparisons were made by a multilevel linear regression analysis. We observed a significant increase in the red fluorescence of the dental plaque after longer periods of formation, but this trend was verified in both groups. The mineral loss assessed by the microhardness techniques, contrariwise, showed a significant increase only in the experimental group. In conclusion, the red fluorescence emitted by the dental plaque indicates a mature biofilm, but this fact is not necessarily associated with its cariogenicity.

In vivo antiplaque efficacy of combined antimicrobial dentifrice and rinse hygiene regimens.

PubMed

White, Donald J; Barker, Matthew L; Klukowska, Malgorzata

2008-06-01

To evaluate using digital plaque image analysis the antiplaque efficacy of oral care regimens including use of antimicrobial toothpaste in combination with antimicrobial mouthrinse. 16 subjects completed the study protocol including: (1) initial treatment phase, all subjects used a standard sodium fluoride dentifrice with 2x/day brushing, (2) second treatment phase, subjects were randomized to two treatment groups: stannous fluoride/sodium hexametaphosphate dentifrice or sodium fluoride triclosan/copolymer dentifrice; (3) third treatment phase, the group using stannous fluoride dentifrice rinsed with alcohol-free cetylpyridinium chloride mouthrinse and the group using triclosan dentifrice rinsed with essential oil mouthrinse. During each phase, plaque levels were assessed in the morning before toothbrushing (AM), post-brushing in the morning (PB) and in the afternoon (PM). Stannous fluoride dentifrice was superior to triclosan dentifrice in plaque growth inhibition between toothbrushing. Both mouthrinses provided additional plaque prevention benefits when used with antimicrobial dentifrices. The cetylpyridinium chloride mouthrinse and stannous fluoride dentifrice regimen was particularly effective, building accretive efficacy over time. Average plaque reductions exceeded 50% vs. sodium fluoride dentifrice alone. Chemotherapeutic dentifrices and rinses increase plaque control used alone and particularly in combination. The stannous fluoride-cetylpyridinium chloride regimen showed the greatest benefits.

Correlations between gene expression highlight a different activation of ACE/TLR4/PTGS2 signaling in symptomatic and asymptomatic plaques in atherosclerotic patients.

PubMed

Ferronato, Silvia; Scuro, Alberto; Gomez-Lira, Macarena; Mazzucco, Sara; Olivato, Silvia; Turco, Alberto; Elisa, Orlandi; Malerba, Giovanni; Romanelli, Maria Grazia

2018-06-19

Inflammation has a key role and translates the effects of many known risk factors for the disease in atherosclerotic vulnerable plaques. Aiming to look into the elements that induce the development of either a vulnerable or stable atherosclerotic plaque, and considering that inflammation has a central role in the progression of lesions, we analyzed the expression of genes involved in the ACE/TLR4/PTGS2 signaling in carotid plaques of symptomatic and asymptomatic patients. Patients with internal carotid artery stenosis undergoing carotid endarterectomy at Verona University Hospital were included in this study. A total of 71 patients was considered for gene expression analysis (29 atherothrombotic stroke patients and 42 asymptomatic patients). Total RNA was extracted from the excised plaques and expression of PTGS2, ACE, TLR4, PTGER4, PTGER3, EPRAP and ACSL4 genes was analyzed by real-time PCR. The correlation between the pair of genes was studied by Spearman coefficient. From the analyzed genes, we did not observe any individual difference in gene expression but the network of co-expressed genes suggests a different activation of pathways in the two groups of plaques.

Predictors of Plaque Rupture Within Nonculprit Fibroatheromas in Patients With Acute Coronary Syndromes: The PROSPECT Study.

PubMed

Zheng, Bo; Mintz, Gary S; McPherson, John A; De Bruyne, Bernard; Farhat, Naim Z; Marso, Steven P; Serruys, Patrick W; Stone, Gregg W; Maehara, Akiko

2015-10-01

The study sought to examine the relative importance of lesion location versus vessel area and plaque burden in predicting plaque rupture within nonculprit fibroatheromas (FAs) in patients with acute coronary syndromes. Previous studies have demonstrated that plaque rupture is associated with larger vessel area and greater plaque burden clustering in the proximal segments of coronary arteries. In the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study 3-vessel grayscale and radiofrequency-intravascular ultrasound was performed after successful percutaneous coronary intervention in 697 patients with acute coronary syndromes. Untreated nonculprit lesion FAs were classified as proximal (<20 mm), mid (20 to 40 mm), and distal (>40 mm) according to the distance from the ostium to the maximum necrotic core site. Overall, 74 ruptured FAs and 2,396 nonruptured FAs were identified in nonculprit vessels. The majority of FAs (73.6%) were located within 40 mm of the ostium, and the vessel area and plaque burden progressively decreased from proximal to distal FA location (both p < 0.001). In a multivariate logistic regression model, independent predictors for plaque rupture included the distance from the ostium to the maximum necrotic core site per millimeter (odds ratio [OR]: 0.86; 95% confidence interval [CI]: 0.76 to 0.98; p = 0.02), plaque burden per 10% (OR: 2.05; 95% CI: 1.63 to 2.58; p < 0.0001), vessel area per mm(2) (OR: 1.14; 95% CI: 1.11 to 1.17; p < 0.0001), calcium (OR: 0.09; 95% CI: 0.05 to 0.18; p < 0.0001), and right coronary artery location (OR: 2.16; 95% CI: 1.25 to 3.27; p = 0.006). By receiver-operating characteristic analysis, vessel area correlated with plaque rupture stronger than either plaque burden (p < 0.001) or location (p < 0.001). Large vessel area, plaque burden, proximal location, right coronary artery location, and lack of calcium were associated with FA plaque rupture. The present study suggests that among these variables, vessel area may be the strongest predictor of plaque rupture among non-left main coronary arteries. ( An Imaging Study in Patients With Unstable Atherosclerotic Lesions [PROSPECT]; NCT00180466). Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

SU-E-T-635: Process Mapping of Eye Plaque Brachytherapy

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

Huynh, J; Kim, Y

Purpose: To apply a risk-based assessment and analysis technique (AAPM TG 100) to eye plaque brachytherapy treatment of ocular melanoma. Methods: The role and responsibility of personnel involved in the eye plaque brachytherapy is defined for retinal specialist, radiation oncologist, nurse and medical physicist. The entire procedure was examined carefully. First, major processes were identified and then details for each major process were followed. Results: Seventy-one total potential modes were identified. Eight major processes (corresponding detailed number of modes) are patient consultation (2 modes), pretreatment tumor localization (11), treatment planning (13), seed ordering and calibration (10), eye plaque assembly (10),more » implantation (11), removal (11), and deconstruction (3), respectively. Half of the total modes (36 modes) are related to physicist while physicist is not involved in processes such as during the actual procedure of suturing and removing the plaque. Conclusion: Not only can failure modes arise from physicist-related procedures such as treatment planning and source activity calibration, but it can also exist in more clinical procedures by other medical staff. The improvement of the accurate communication for non-physicist-related clinical procedures could potentially be an approach to prevent human errors. More rigorous physics double check would reduce the error for physicist-related procedures. Eventually, based on this detailed process map, failure mode and effect analysis (FMEA) will identify top tiers of modes by ranking all possible modes with risk priority number (RPN). For those high risk modes, fault tree analysis (FTA) will provide possible preventive action plans.« less

Multi-contrast MRI registration of carotid arteries based on cross-sectional images and lumen boundaries

NASA Astrophysics Data System (ADS)

Wu, Yu-Xia; Zhang, Xi; Xu, Xiao-Pan; Liu, Yang; Zhang, Guo-Peng; Li, Bao-Juan; Chen, Hui-Jun; Lu, Hong-Bing

2017-02-01

Ischemic stroke has great correlation with carotid atherosclerosis and is mostly caused by vulnerable plaques. It's particularly important to analysis the components of plaques for the detection of vulnerable plaques. Recently plaque analysis based on multi-contrast magnetic resonance imaging has attracted great attention. Though multi-contrast MR imaging has potentials in enhanced demonstration of carotid wall, its performance is hampered by the misalignment of different imaging sequences. In this study, a coarse-to-fine registration strategy based on cross-sectional images and wall boundaries is proposed to solve the problem. It includes two steps: a rigid step using the iterative closest points to register the centerlines of carotid artery extracted from multi-contrast MR images, and a non-rigid step using the thin plate spline to register the lumen boundaries of carotid artery. In the rigid step, the centerline was extracted by tracking the crosssectional images along the vessel direction calculated by Hessian matrix. In the non-rigid step, a shape context descriptor is introduced to find corresponding points of two similar boundaries. In addition, the deterministic annealing technique is used to find a globally optimized solution. The proposed strategy was evaluated by newly developed three-dimensional, fast and high resolution multi-contrast black blood MR imaging. Quantitative validation indicated that after registration, the overlap of two boundaries from different sequences is 95%, and their mean surface distance is 0.12 mm. In conclusion, the proposed algorithm has improved the accuracy of registration effectively for further component analysis of carotid plaques.

High resolution magnetic resonance imaging in pathogenesis diagnosis of single lenticulostriate infarction with nonstenotic middle cerebral artery, a retrospective study.

PubMed

Sun, Li-Li; Li, Zhong-Hao; Tang, Wen-Xiong; Liu, Lei; Chang, Fei-Yan; Zhang, Xue-Bin; Ye, Wei-Jie; Lu, Shuo; Liu, Zun-Jing; Zhu, Xian-Jin

2018-04-25

It is usually difficult to identify stroke pathogenesis for single lenticulostriate infarction with nonstenotic middle cerebral artery (MCA). Our aim is to differentiate the two pathogeneses, non-branch atheromatous small vessel disease and branch atheromatous disease (BAD) by high-resolution magnetic resonance imaging (HR-MRI). Thirty-two single lenticulostriate infarction patients with nonstenotic MCA admitted to the China-Japan Friendship Hospital from December 2014 to August 2017 were enrolled for retrospective analysis. National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), atherosclerotic risk factors, imaging features, and the characteristic of MCA vessel wall in HR-MRI were evaluated. MCA plaques were detected in 15(46.9%) patients which implied BAD and 8 of 15 (53.3%) patients had plaques location in upper dorsal side of the vessel wall. Patients with HR-MRI identified plaques had a significantly larger infarction lesion length (1.95 ± 0.86 cm versus 1.38 ± 0.55 cm; P = 0.031) and larger lesion volume (2.95 ± 3.94 cm 3 versus 0.90 ± 0.94 cm 3 ; P = 0.027) than patients without plaques. Patients with HR-MRI identified plaques had a significant higher percentage of proximal lesions than patients without plaques (P = 0.055). However, according to the location of MCA plaques, there were no significant differences in terms of imaging features, NIHSS and mRS. We demonstrated high frequency of MCA atheromatous plaques visualized in single lenticulostriate infarction patients with nonstenotic MCA by using HR-MRI. Patients with HR-MRI identified plaque presented larger infarction lesions and more proximal lesions than patients without plaque, which were consistent with imaging features of BAD. HR-MRI is an important and effective tool for identifying stroke etiology in patients with nonstenotic MCA.

Spatio-temporal texture (SpTeT) for distinguishing vulnerable from stable atherosclerotic plaque on dynamic contrast enhancement (DCE) MRI in a rabbit model

PubMed Central

Wan, Tao; Madabhushi, Anant; Phinikaridou, Alkystis; Hamilton, James A.; Hua, Ning; Pham, Tuan; Danagoulian, Jovanna; Kleiman, Ross; Buckler, Andrew J.

2014-01-01

Purpose: To develop a new spatio-temporal texture (SpTeT) based method for distinguishing vulnerable versus stable atherosclerotic plaques on DCE-MRI using a rabbit model of atherothrombosis. Methods: Aortic atherosclerosis was induced in 20 New Zealand White rabbits by cholesterol diet and endothelial denudation. MRI was performed before (pretrigger) and after (posttrigger) inducing plaque disruption with Russell's-viper-venom and histamine. Of the 30 vascular targets (segments) under histology analysis, 16 contained thrombus (vulnerable) and 14 did not (stable). A total of 352 voxel-wise computerized SpTeT features, including 192 Gabor, 36 Kirsch, 12 Sobel, 52 Haralick, and 60 first-order textural features, were extracted on DCE-MRI to capture subtle texture changes in the plaques over the course of contrast uptake. Different combinations of SpTeT feature sets, in which the features were ranked by a minimum-redundancy-maximum-relevance feature selection technique, were evaluated via a random forest classifier. A 500 iterative 2-fold cross validation was performed for discriminating the vulnerable atherosclerotic plaque and stable atherosclerotic plaque on per voxel basis. Four quantitative metrics were utilized to measure the classification results in separating between vulnerable and stable plaques. Results: The quantitative results show that the combination of five classes of SpTeT features can distinguish between vulnerable (disrupted plaques with an overlying thrombus) and stable plaques with the best AUC values of 0.9631 ± 0.0088, accuracy of 89.98% ± 0.57%, sensitivity of 83.71% ± 1.71%, and specificity of 94.55% ± 0.48%. Conclusions: Vulnerable and stable plaque can be distinguished by SpTeT based features. The SpTeT features, following validation on larger datasets, could be established as effective and reliable imaging biomarkers for noninvasively assessing atherosclerotic risk. PMID:24694153

Vaspin attenuates the progression of atherosclerosis by inhibiting ER stress-induced macrophage apoptosis in apoE−/− mice

PubMed Central

LIN, YING; ZHUANG, JIANHUI; LI, HAILING; ZHU, GUOFU; ZHOU, SHUNPING; LI, WEIMING; PENG, WENHUI; XU, YAWEI

2016-01-01

Visceral adipose tissue-derived serine protease inhibitor (vaspin) is a novel adipokine with potential insulin-sensitizing properties, which was initially detected in the visceral adipose tissue of genetically obese rats. Previous studies have demonstrated that vaspin exerts a protective effect on arteries undergoing atherosclerosis in vitro, and it has been shown to exert anti-inflammatory and antimigratory effects on vascular smooth muscle cells. Vaspin promotes proliferation and inhibits apoptosis in endothelial cells, and decreases proliferation of the arterial intima under diabetic conditions. In addition, macrophage apoptosis is an important characteristic of atherosclerotic plaque development. In vivo experiments were performed by histological analysis, including Oil Red O, hematoxylin and eosin and Masson's trichrome staining. Mice were injected with lentivirus via the tail vein and tissues were obtained for histological analysis. Cell apoptosis was determined by flow cytometry of Annexin-V/propidium iodide dual staining and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling assay. Total proteins were extracted and protein expression levels were detected by western blot analysis. The present study aimed to investigate whether vaspin was able to protect against atherosclerotic development in vivo, and to explore the underlying mechanisms of the potential antiatherogenic effects. The results of the current study indicated that vaspin inhibited the progression of atherosclerotic plaques in apoE−/− mice by inhibiting endoplasmic reticulum stress-induced macrophage apoptosis. PMID:26708512

Short-term effect of mechanical plaque control on salivary mutans streptococci in preschool children.

PubMed

Liu, Min; Ge, Lihong; Zheng, Shuguo; Yuan, Chao; Zhang, Bo; Xu, Tao

2014-01-01

To determine the effect of mechanical tooth cleaning by toothbrush and dental floss on mutans streptococci in the saliva of preschool children. This blinded, randomised controlled clinical trial included 54 3-year-old preschool children with detectable mutans streptococci in saliva. The children were randomly divided into a test and a control group. Dental college students cleaned the teeth of test group participants with toothbrush and dental floss under the indication of a plaque disclosing agent once a day. The control group received no intervention. Dentocult SM Strip mutans (D-SM) strips were used to test the mutans streptococci in saliva. The D-SM test scores declined from 1.82 to 0.95 for the test group after the teeth were cleaned 10 times (P < 0.001) and the scores increased to 1.62 after tooth cleaning ceased for 2 weeks (P > 0.05 compared with baseline). The D-SM level of the control group did not change significantly. Meticulous and continuous plaque control with toothbrush and dental floss can decrease the mutans streptococci level in preschool children. However, the effect ceased as the intervention ceased.

Novel anti-microbial therapies for dental plaque-related diseases.

PubMed

Allaker, Robert P; Douglas, C W Ian

2009-01-01

Control of dental plaque-related diseases has traditionally relied on non-specific removal of plaque by mechanical means. As our knowledge of oral disease mechanisms increases, future treatment is likely to be more targeted, for example at small groups of organisms, single species or at key virulence factors they produce. The aim of this review is to consider the current status as regards novel treatment approaches. Maintenance of oral hygiene often includes use of chemical agents; however, increasing problems of resistance to synthetic antimicrobials have encouraged the search for alternative natural products. Plants are the source of more than 25% of prescription and over-the-counter preparations, and the potential of natural agents for oral prophylaxis will therefore be considered. Targeted approaches may be directed at the black-pigmented anaerobes associated with periodontitis. Such pigments provide an opportunity for targeted phototherapy with high-intensity monochromatic light. Studies to date have demonstrated selective killing of Porphyromonas gingivalis and Prevotella intermedia in biofilms. Functional inhibition approaches, including the use of protease inhibitors, are also being explored to control periodontitis. Replacement therapy by which a resident pathogen is replaced with a non-pathogenic bacteriocin-producing variant is currently under development with respect to Streptococcus mutans and dental caries.

Abnormal Thiamine-Dependent Processes in Alzheimer’s Disease. Lessons from Diabetes

PubMed Central

Gibson, Gary E.; Hirsch, Joseph A.; Cirio, Rosanna T.; Jordan, Barry D.; Fonzetti, Pasquale; Elder, Jessica

2013-01-01

Reduced glucose metabolism is an invariant feature of Alzheimer’s Disease (AD) and an outstanding biomarker of disease progression. Glucose metabolism may be an attractive therapeutic target, whether the decline initiates AD pathophysiology or is a critical component of a cascade. The cause of cerebral regional glucose hypometabolism remains unclear. Thiamine-dependent processes are critical in glucose metabolism and are diminished in brains of AD patients at autopsy. Further, the reductions in thiamine-dependent processes are highly correlated to the decline in clinical dementia rating scales. In animal models, thiamine deficiency exacerbates plaque formation, promotes phosphorylation of tau and impairs memory. In contrast, treatment of mouse models of AD with the thiamine derivative benfotiamine diminishes plaques, decreases phosphorylation of tau and reverses memory deficits. Diabetes predisposes to AD, which suggests they may share some common mechanisms. Benfotiamine diminishes peripheral neuropathy in diabetic humans and animals. In diabetes, benfotiamine induces key thiamine-dependent enzymes of the pentose shunt to reduce accumulation of toxic metabolites including advanced glycation end products (AGE). Related mechanisms may lead to reversal of plaque formation by benfotiamine in animals. If so, the use of benfotiamine could provide a safe intervention to reverse biological and clinical processes of AD progression. PMID:22982063

Mechanism of lumen gain with a novel rotational aspiration atherectomy system for peripheral arterial disease: examination by intravascular ultrasound.

PubMed

Hassan, Ali H M; Ako, Junya; Waseda, Katsuhisa; Honda, Yasuhiro; Zeller, Thomas; Leon, Martin B; Fitzgerald, Peter J

2010-01-01

The purpose of this study was to evaluate the mechanism of luminal gain with a novel atheroablation system (Pathway PV) for the treatment of peripheral artery disease using intravascular ultrasound (IVUS). The atherectomy system is a rotational atherectomy device, which employs expandable rotating blades with ports that allow flushing and aspiration of the plaque material or thrombus. In this first-in-man clinical study, IVUS analysis was available in 6 patients with lower limb ischemia treated with this device. The treatment results were assessed using IVUS at pre and post atherectomy. Lumen beyond burr size (LBB) was defined as lumen gain divided by the estimated burr area determined by the burr-size. IVUS analysis was available in six patients (superficial femoral artery n=3, popliteal artery n=2, posterior tibial artery n=1). Atheroablation achieved a significant increase in lumen area (LA) (preintervention 3.9+/-0.4, postatheroablation 8.0+/-1.7 mm(2), P<.05), and significant reduction in plaque area (27.5+/-4.0, 23.7+/-3.1 mm(2), P=.001), while there was no change in the vessel area (31.3+/-4.2, 32.1+/-2.8 mm(2), P=.4). LBB was 57.4+/-51.3%. This novel rotational aspiration atherectomy device achieved significant luminal gain by debulking in the absence of vessel stretching. The LA was greater than burr-sized lumen expectancy at cross-sections along the treated segments, suggesting a complimentary role of aspiration in luminal gain in atherosclerotic peripheral artery lesions.

Debulking Atherectomy in the Peripheral Arteries: Is There a Role and What is the Evidence?

PubMed

Katsanos, Konstantinos; Spiliopoulos, Stavros; Reppas, Lazaros; Karnabatidis, Dimitris

2017-07-01

Traditional percutaneous balloon angioplasty and stent placement is based on mechanical plaque disruption and displacement within the arterial wall. On the contrary, transcatheter atherectomy achieves atherosclerotic plaque clearance by means of directional plaque excision or rotational plaque removal or laser plaque ablation. Debulking atherectomy may allow for a more uniform angioplasty result at lower pressures with consequently less vessel barotrauma and improved luminal gain, thereby decreasing the risk of plaque recoil and dissection that may require permanent metal stenting. It has been also argued that atherectomy may disrupt the calcium barrier and optimize drug transfer and delivery in case of drug-coated balloon applications. The authors discuss the various types of atherectomy devices available in clinical practice to date and critically appraise their mode of action as well as relevant published data in each case. Overall, amassed randomized and observational evidence indicates that percutaneous atherectomy of the femoropopliteal and infrapopliteal arteries may achieve high technical success rates and seems to lessen the frequency of bailout stenting, however, at the expense of increased risk of peri-procedural distal embolization. Long-term clinical outcomes reported to date do not support the superiority of percutaneous atherectomy over traditional balloon angioplasty and stent placement in terms of vessel patency or limb salvage. The combination of debulking atherectomy and drug-coated balloons has shown promise in early studies, especially in the treatment of more complex lesions. Unanswered questions and future perspectives of this continuously evolving endovascular technology as part of a broader treatment algorithm are discussed.

Classification of human coronary atherosclerotic plaques using ex vivo high-resolution multicontrast-weighted MRI compared with histopathology.

PubMed

Li, Tao; Li, Xin; Zhao, Xihai; Zhou, Weihua; Cai, Zulong; Yang, Li; Guo, Aitao; Zhao, Shaohong

2012-05-01

The objective of our study was to evaluate the feasibility of ex vivo high-resolution multicontrast-weighted MRI to accurately classify human coronary atherosclerotic plaques according to the American Heart Association classification. Thirteen human cadaver heart specimens were imaged using high-resolution multicontrast-weighted MR technique (T1-weighted, proton density-weighted, and T2-weighted). All MR images were matched with histopathologic sections according to the landmark of the bifurcation of the left main coronary artery. The sensitivity and specificity of MRI for the classification of plaques were determined, and Cohen's kappa analysis was applied to evaluate the agreement between MRI and histopathology in the classification of atherosclerotic plaques. One hundred eleven MR cross-sectional images obtained perpendicular to the long axis of the proximal left anterior descending artery were successfully matched with the histopathologic sections. For the classification of plaques, the sensitivity and specificity of MRI were as follows: type I-II (near normal), 60% and 100%; type III (focal lipid pool), 80% and 100%; type IV-V (lipid, necrosis, fibrosis), 96.2% and 88.2%; type VI (hemorrhage), 100% and 99.0%; type VII (calcification), 93% and 100%; and type VIII (fibrosis without lipid core), 100% and 99.1%, respectively. Isointensity, which indicates lipid composition on histopathology, was detected on MRI in 48.8% of calcified plaques. Agreement between MRI and histopathology for plaque classification was 0.86 (p < 0.001). Ex vivo high-resolution multicontrast-weighted MRI can accurately classify advanced atherosclerotic plaques in human coronary arteries.

Impact of the Distance from the Stent Edge to the Residual Plaque on Edge Restenosis following Everolimus-Eluting Stent Implantation

PubMed Central

Myojo, Masahiro; Sawaki, Daigo; Iwata, Hiroshi; Kiyosue, Arihiro; Higashikuni, Yasutomi; Tanaka, Tomofumi; Fujita, Daishi; Ando, Jiro; Fujita, Hideo; Hirata, Yasunobu; Komuro, Issei

2015-01-01

Objectives This study aimed to assess the relation between stent edge restenosis (SER) and the distance from the stent edge to the residual plaque using quantitative intravascular ultrasound. Background Although percutaneous coronary intervention with drug-eluting stents has improved SER rates, determining an appropriate stent edge landing zone can be challenging in cases of diffuse plaque lesions. It is known that edge vascular response can occur within 2 mm from the edge of a bare metal stent, but the distance to the adjacent plaque has not been evaluated for drug-eluting stents. Methods A total of 97 proximal residual plaque lesions (plaque burden [PB] >40%) treated with everolimus-eluting stents were retrospectively evaluated to determine the distance from the stent edge to the residual plaque. Results The SER group had significantly higher PB (59.1 ± 6.1% vs. 51.9 ± 9.1% for non-SER; P = 0.04). Higher PB was associated with SER, with the cutoff value of 54.74% determined using receiver operating characteristic (ROC) curve analysis. At this cutoff value of PB, the distance from the stent edge to the lesion was significantly associated with SER (odds ratio = 2.05, P = 0.035). The corresponding area under the ROC curve was 0.725, and the cutoff distance value for predicting SER was 1.0 mm. Conclusion An interval less than 1 mm from the proximal stent edge to the nearest point with the determined PB cutoff value of 54.74% was significantly associated with SER in patients with residual plaque lesions. PMID:25775115

Occurrence of Helicobacter pylori and its major virulence genotypes in dental plaque samples of patients with chronic periodontitis in Iran

PubMed Central

Valadan Tahbaz, Sahel; Yadegar, Abbas; Amirmozafari, Nour; Yaghoobee, Siamak; Ehsani Ardakani, Mohammad Javad; Zojaji, Homayoun

2017-01-01

Aim: This study was aimed to investigate the presence of H. pylori and its virulence genotypes in dental plaques of Iranian patients with chronic periodontitis. Background: Helicobacter pylori is a Gram-negative bacterium that is associated with atrophic gastritis, peptic ulcer, and gastric cancer. Several studies have detected this bacterium in the oral cavity, suggesting it as a potential reservoir. Methods: A hundred individuals were divided in 2 groups: 50 patients with chronic periodontitis (case group), and 50 subjects in non-periodontitis (control group). Supragingival and subgingival plaque samples were collected from the individuals using wood wedges and sterile paper points respectively, and prepared for PCR analysis. Results: Totally, H. pylori DNA was detected in 5 out of 100 (5%) dental plaques. Of 5 dental plaques positive for H. pylori, cagA gene was detected in 4 specimen, 3 in periodontitis group and one in non-periodontitis group. The H. pylori vacA s1m1 genotype was predominantly detected in 2/5 samples. The babA2 gene was detected in all (5/5) H. pylori-positive dental plaques. There was no significant correlation between the presence of H. pylori genotypes from dental plaques and chronic periodontitis (P > 0.05). Conclusion: Our results revealed that the rate of H. pylori is very low in the dental plaques of Iranian patients with chronic periodontitis. Majority of H. pylori strains from oral cavity were highly virulent based on the main clinically virulence factors they carried. PMID:29511475

Impact of the distance from the stent edge to the residual plaque on edge restenosis following everolimus-eluting stent implantation.

PubMed

Takahashi, Masao; Miyazaki, Susumu; Myojo, Masahiro; Sawaki, Daigo; Iwata, Hiroshi; Kiyosue, Arihiro; Higashikuni, Yasutomi; Tanaka, Tomofumi; Fujita, Daishi; Ando, Jiro; Fujita, Hideo; Hirata, Yasunobu; Komuro, Issei

2015-01-01

This study aimed to assess the relation between stent edge restenosis (SER) and the distance from the stent edge to the residual plaque using quantitative intravascular ultrasound. Although percutaneous coronary intervention with drug-eluting stents has improved SER rates, determining an appropriate stent edge landing zone can be challenging in cases of diffuse plaque lesions. It is known that edge vascular response can occur within 2 mm from the edge of a bare metal stent, but the distance to the adjacent plaque has not been evaluated for drug-eluting stents. A total of 97 proximal residual plaque lesions (plaque burden [PB] >40%) treated with everolimus-eluting stents were retrospectively evaluated to determine the distance from the stent edge to the residual plaque. The SER group had significantly higher PB (59.1 ± 6.1% vs. 51.9 ± 9.1% for non-SER; P = 0.04). Higher PB was associated with SER, with the cutoff value of 54.74% determined using receiver operating characteristic (ROC) curve analysis. At this cutoff value of PB, the distance from the stent edge to the lesion was significantly associated with SER (odds ratio = 2.05, P = 0.035). The corresponding area under the ROC curve was 0.725, and the cutoff distance value for predicting SER was 1.0 mm. An interval less than 1 mm from the proximal stent edge to the nearest point with the determined PB cutoff value of 54.74% was significantly associated with SER in patients with residual plaque lesions.

Absence of Akt1 reduces vascular smooth muscle cell migration and survival and induces features of plaque vulnerability and cardiac dysfunction during atherosclerosis

PubMed Central

Fernández-Hernando, Carlos; József, Levente; Jenkins, Deborah; Lorenzo, Annarita Di; Sessa, William C.

2009-01-01

Objective Deletion of Akt1 leads to severe atherosclerosis and occlusive coronary artery disease. VSMC are an important component of atherosclerotic plaques, responsible for promoting plaque stability in advanced lesions. Fibrous caps of unstable plaques contain less collagen and ECM components and fewer VSMCs than caps from stable lesions. Here, we investigated the role of Akt1 in VSMC proliferation, migration and oxidative stress-induce apoptosis. In addition, we also characterized the atherosclerotic plaque morphology and cardiac function in an atherosclerosis-prone mouse model deficient in Akt1. Methods and Results Absence of Akt1 reduces VSMC proliferation and migration. Mechanistically, the proliferation and migratory phenotype found in Akt1 null VSMCs was linked to reduced Rac-1 activity and MMP-2 secretion. Serum starvation and stress-induced apoptosis was enhanced in Akt1 null VSMCs as determined by flow cytometry using Annexin V/PI staining. Immunohistochemical analysis of atherosclerotic plaques from Akt1−/−ApoE−/− mice showed a dramatic increase in plaque vulnerability characteristics such as enlarged necrotic core and reduced fibrous cap and collagen content. Finally, we show evidences of myocardial infarcts and cardiac dysfunction in Akt1−/−ApoE−/− mice analyzed by immunohistochemistry and echocardiography respectively. Conclusion Akt1 is essential for VSMC proliferation, migration and protection against oxidative stress-induce apoptosis. Absence of Akt1 induces features of plaque vulnerability and cardiac dysfunction in a mouse model of atherosclerosis. PMID:19762778

Ultrasound analysis of gray-scale median value of carotid plaques is a useful reference index for cerebro-cardiovascular events in patients with type 2 diabetes.

PubMed

Ariyoshi, Kyoko; Okuya, Shigeru; Kunitsugu, Ichiro; Matsunaga, Kimie; Nagao, Yuko; Nomiyama, Ryuta; Takeda, Komei; Tanizawa, Yukio

2015-01-01

Measurements of plaque echogenicity, the gray-scale median (GSM), were shown to correlate inversely with risk factors for cerebro-cardiovascular disease (CVD). The eicosapentaenoic acid (EPA)/arachidonic acid (AA) ratio is a potential predictor of CVD risk. In the present study, we assessed the usefulness of carotid plaque GSM values and EPA/AA ratios in atherosclerotic diabetics. A total of 84 type 2 diabetics with carotid artery plaques were enrolled. On admission, platelet aggregation and lipid profiles, including EPA and AA, were examined. Using ultrasound, mean intima media thickness and plaque score were measured in carotid arteries. Plaque echogenicity was evaluated using computer-assisted quantification of GSM. The patients were then further observed for approximately 3 years. Gray-scale median was found to be a good marker of CVD events. On multivariate logistic regression analysis, GSM <32 and plaque score ≥5 were significantly associated with past history and onset of CVD during the follow-up period, the odds ratios being 7.730 (P = 0.014) and 4.601 (P = 0.046), respectively. EPA/AA showed a significant correlation with GSM (P = 0.012) and high-density lipoprotein cholesterol (P = 0.039), and an inverse correlation with platelet aggregation (P = 0.046) and triglyceride (P = 0.020). Although most patients with CVD had both low GSM and low EPA/AA values, an association of EPA/AA with CVD events could not be statistically confirmed. The present results suggest the GSM value to be useful as a reference index for CVD events in high-risk atherosclerotic diabetics. Associations of the EPA/AA ratio with known CVD risk factors warrant a larger and more extensive study to show the usefulness of this parameter.

Ultrasound analysis of gray-scale median value of carotid plaques is a useful reference index for cerebro-cardiovascular events in patients with type 2 diabetes

PubMed Central

Ariyoshi, Kyoko; Okuya, Shigeru; Kunitsugu, Ichiro; Matsunaga, Kimie; Nagao, Yuko; Nomiyama, Ryuta; Takeda, Komei; Tanizawa, Yukio

2015-01-01

Aims/Introduction Measurements of plaque echogenicity, the gray-scale median (GSM), were shown to correlate inversely with risk factors for cerebro-cardiovascular disease (CVD). The eicosapentaenoic acid (EPA)/arachidonic acid (AA) ratio is a potential predictor of CVD risk. In the present study, we assessed the usefulness of carotid plaque GSM values and EPA/AA ratios in atherosclerotic diabetics. Materials and Methods A total of 84 type 2 diabetics with carotid artery plaques were enrolled. On admission, platelet aggregation and lipid profiles, including EPA and AA, were examined. Using ultrasound, mean intima media thickness and plaque score were measured in carotid arteries. Plaque echogenicity was evaluated using computer-assisted quantification of GSM. The patients were then further observed for approximately 3 years. Results Gray-scale median was found to be a good marker of CVD events. On multivariate logistic regression analysis, GSM <32 and plaque score ≥5 were significantly associated with past history and onset of CVD during the follow-up period, the odds ratios being 7.730 (P = 0.014) and 4.601 (P = 0.046), respectively. EPA/AA showed a significant correlation with GSM (P = 0.012) and high-density lipoprotein cholesterol (P = 0.039), and an inverse correlation with platelet aggregation (P = 0.046) and triglyceride (P = 0.020). Although most patients with CVD had both low GSM and low EPA/AA values, an association of EPA/AA with CVD events could not be statistically confirmed. Conclusions The present results suggest the GSM value to be useful as a reference index for CVD events in high-risk atherosclerotic diabetics. Associations of the EPA/AA ratio with known CVD risk factors warrant a larger and more extensive study to show the usefulness of this parameter. PMID:25621138

Synthesis and Preliminary Evaluation of Phenyl 4-123I-Iodophenylcarbamate for Visualization of Cholinesterases Associated with Alzheimer Disease Pathology.

PubMed

Macdonald, Ian R; Reid, G Andrew; Pottie, Ian R; Martin, Earl; Darvesh, Sultan

2016-02-01

Acetylcholinesterase and butyrylcholinesterase accumulate with brain β-amyloid (Aβ) plaques in Alzheimer disease (AD). The overall activity of acetylcholinesterase is found to decline in AD, whereas butyrylcholinesterase has been found to either increase or remain the same. Although some cognitively normal older adults also have Aβ plaques within the brain, cholinesterase-associated plaques are generally less abundant in such individuals. Thus, brain imaging of cholinesterase activity associated with Aβ plaques has the potential to distinguish AD from cognitively normal older adults, with or without Aβ accumulation, during life. Current Aβ imaging agents are not able to provide this distinction. To address this unmet need, synthesis and evaluation of a cholinesterase-binding ligand, phenyl 4-(123)I-iodophenylcarbamate ((123)I-PIP), is described. Phenyl 4-iodophenylcarbamate was synthesized and evaluated for binding potency toward acetylcholinesterase and butyrylcholinesterase using enzyme kinetic analysis. This compound was subsequently rapidly radiolabeled with (123)I and purified by high-performance liquid chromatography. Autoradiographic analyses were performed with (123)I-PIP using postmortem orbitofrontal cortex from cognitively normal and AD human brains. Comparisons were made with an Aβ imaging agent, 2-(4'-dimethylaminophenyl)-6-(123)I-iodo-imidazo[1,2-a]pyridine ((123)I-IMPY), in adjacent brain sections. Tissues were also stained for Aβ and cholinesterase activity to visualize Aβ plaque load for comparison with radioligand uptake. Synthesized and purified PIP exhibited binding to cholinesterases. (123)I was successfully incorporated into this ligand. (123)I-PIP autoradiography with human tissue revealed accumulation of radioactivity only in AD brain tissues in which Aβ plaques had cholinesterase activity. (123)I-IMPY accumulated in brain tissues with Aβ plaques from both AD and cognitively normal individuals. Radiolabeled ligands specific for cholinesterases have potential for use in neuroimaging AD plaques during life. The compound herein described, (123)I-PIP, can detect cholinesterases associated with Aβ plaques and can distinguish AD brain tissues from those of cognitively normal older adults with Aβ plaques. Imaging cholinesterase activity associated with Aβ plaques in the living brain may contribute to the definitive diagnosis of AD during life. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

[Influence of the fluoride releasing dental materials on the bacterial flora of dental plaque].

PubMed

Płuciennik, Małgorzata; Sakowska, Danuta; Krzemiński, Zbigniew; Piatowska, Danuta

2008-01-01

The assessment of influence of silver-free, fluor releasing dental materials on dental plaque bacteria quantity. 17 patients were included into the study. 51 restorations were placed following manufacturers recommendations. Following materials were used: conventional glassionomer Ketac-Molar ESPE, resin modified glassionomer Fuji II LC GC and fluor containing composite Charisma Heraeus Kulzer Class V restorations were placed in following teeth of upper and lower jaw: canines, first bicuspids, second bicuspids. Sound enamel was a control. After 10 weeks the 72 hours old dental plaque was collected from surface of restorations and control using sterile probe. Total amount of 68 dental plaques were investigated. Each plaque was placed on scaled and sterile aluminum foil. The moist weight of dental plaque was scaled. Dental plaque was moved into 7 ml 0.85% NaCl solution reduced by cystein chlorine hydrogen and disintegrated by ultrasounds (power:100 Watt, wave amplitude: 5 micorm). The suspension of dental plaque was serially diluted from 10(-4) to 10(-5) in sterile 0,85% NaCl solution, and seeded with amount of 0.1 ml on appropriate base. In dental plaque trials the amount of cariogenic bacteria was calculated--Streptococcus mutans, Streptococcus, Lactobacillus, Veillonella and Neisseria, and also total amount of aerobic and anaerobic bacteria was measured. Microbiologic studies were performed in Institute of Microbiology, Medical University, Łódź. Statistical analysis of collected data was accomplished. In 72 hours old dental plaques collected from the surfaces of Ketac -Molar, Fuji II LC, Charisma after 10 weeks since being placed into the class V cavity, results show no statistically significant differences in the amount of Streptococcus mutans, Streptococcus spp., Lactobacillus spp., Veillonella spp., Neisseria spp, in total amount of aerobic and anaerobic bacteria and in the quantity proportion of Streptococcus mutans versus Streptococcus spp. in comparison with control trail. Results show no statistically significant differences in the amount of listed above bacteria and in the proportion of Streptococcus mutans versus Streptococcus spp. in 72 hours old dental plaques collected from surfaces of investigated restorative materials.

An efficient two-stage approach for image-based FSI analysis of atherosclerotic arteries

PubMed Central

Rayz, Vitaliy L.; Mofrad, Mohammad R. K.; Saloner, David

2010-01-01

Patient-specific biomechanical modeling of atherosclerotic arteries has the potential to aid clinicians in characterizing lesions and determining optimal treatment plans. To attain high levels of accuracy, recent models use medical imaging data to determine plaque component boundaries in three dimensions, and fluid–structure interaction is used to capture mechanical loading of the diseased vessel. As the plaque components and vessel wall are often highly complex in shape, constructing a suitable structured computational mesh is very challenging and can require a great deal of time. Models based on unstructured computational meshes require relatively less time to construct and are capable of accurately representing plaque components in three dimensions. These models unfortunately require additional computational resources and computing time for accurate and meaningful results. A two-stage modeling strategy based on unstructured computational meshes is proposed to achieve a reasonable balance between meshing difficulty and computational resource and time demand. In this method, a coarsegrained simulation of the full arterial domain is used to guide and constrain a fine-scale simulation of a smaller region of interest within the full domain. Results for a patient-specific carotid bifurcation model demonstrate that the two-stage approach can afford a large savings in both time for mesh generation and time and resources needed for computation. The effects of solid and fluid domain truncation were explored, and were shown to minimally affect accuracy of the stress fields predicted with the two-stage approach. PMID:19756798

Mildly elevated serum total bilirubin levels are negatively associated with carotid atherosclerosis among elderly persons with type 2 diabetes.

PubMed

Kawamoto, Ryuichi; Ninomiya, Daisuke; Hasegawa, Yoichi; Kasai, Yoshihisa; Kusunoki, Tomo; Ohtsuka, Nobuyuki; Kumagi, Teru; Abe, Masanori

2016-01-01

Diabetes is strongly associated with several mechanisms of tissue damage such as oxidative stress. Serum bilirubin may have a beneficial role in preventing oxidative changes in cardiovascular disease (CVD). Limited information is available on whether serum bilirubin is an independent confounding factor for carotid atherosclerosis among elderly persons with type 2 diabetes. The study subjects were 169 men aged 79 ± 8 (mean ± SD) years and 205 women aged 81 ± 8 years that were enrolled consecutively from patients in the medical department. Carotid intima-media thickness (IMT) and plaque were derived via B-mode ultrasonography. Multiple linear regression analysis showed that serum total bilirubin (β = -0.160) was significantly associated with carotid IMT. Compared to subjects with a serum total bilirubin of tertile-1 (0.13-0.58 mg/dL), the multivariate-adjusted odds ratio (95% confidence interval) of carotid IMT ≥1.0 mm including plaque and carotid plaque was 0.46 (0.23-0.93) and 0.32 (0.17-0.60) in the Tertile-3 group (0.87-1.93 mg/dL), respectively. Next, data were further stratified by gender, age, smoking status, medication and prevalence of CVD. There were no significant differences in serum total bilirubin levels between selected subgroups. Our data demonstrated a negative association between serum total bilirubin and carotid atherosclerosis among elderly persons with type 2 diabetes.

Amyloid deposition in the hippocampus and entorhinal cortex: Quantitative analysis of a transgenic mouse model

PubMed Central

Reilly, John F.; Games, Dora; Rydel, Russell E.; Freedman, Stephen; Schenk, Dale; Young, Warren G.; Morrison, John H.; Bloom, Floyd E.

2003-01-01

Various transgenic mouse models of Alzheimer's disease (AD) have been developed that overexpress mutant forms of amyloid precursor protein in an effort to elucidate more fully the potential role of β-amyloid (Aβ) in the etiopathogenesis of the disease. The present study represents the first complete 3D reconstruction of Aβ in the hippocampus and entorhinal cortex of PDAPP transgenic mice. Aβ deposits were detected by immunostaining and thioflavin fluorescence, and quantified by using high-throughput digital image acquisition and analysis. Quantitative analysis of amyloid load in hippocampal subfields showed a dramatic increase between 12 and 15 months of age, with little or no earlier detectable deposition. Three-dimensional reconstruction in the oldest brains visualized previously unrecognized sheets of Aβ coursing through the hippocampus and cerebral cortex. In contrast with previous hypotheses, compact plaques form before significant deposition of diffuse Aβ, suggesting that different mechanisms are involved in the deposition of diffuse amyloid and the aggregation into plaques. The dentate gyrus was the hippocampal subfield with the greatest amyloid burden. Sublaminar distribution of Aβ in the dentate gyrus correlated most closely with the termination of afferent projections from the lateral entorhinal cortex, mirroring the selective vulnerability of this circuit in human AD. This detailed temporal and spatial analysis of Aβ and compact amyloid deposition suggests that specific corticocortical circuits express selective, but late, vulnerability to the pathognomonic markers of amyloid deposition, and can provide a basis for detecting prior vulnerability factors. PMID:12697936

Periodontal Status in Smokers and Nonsmokers: A Clinical, Microbiological, and Histopathological Study

PubMed Central

Sreedevi, Maddipati; Ramesh, Alampalli; Dwarakanath, Chini

2012-01-01

A case-control study was done to assess the influence of smoking on clinical, microbiological, and histopathological parameters. Methods. Two hundred dentate male patients (100 smokers and 100 nonsmokers) ranging between 25 and 50 years were enrolled in the study. Periodontal parameters were recorded. Plaque samples were collected for microbial analysis for BANA test. Gingival biopsies were obtained from selected site for assessing histopathological changes. Results. Both groups showed almost similar plaque levels (P=0.258), but smokers had reduced gingival (0.62 ± 0.31) and bleeding indices (28.53 ± 17.52) and an increased calculus index (1.62 ± 0.36). Smokers had an increased probing depth of 4–7 mm (P=0.009) and overall increased CAL. No difference in microbiota was found between the two groups. Histopathologically smokers showed a decreased blood vessel density (8.84 ± 0.96) and inflammatory cells (52.00 ± 9.79). Conclusions. It is quite possible that many of the pathogenic mechanisms involved in tissue degradation in periodontitis in smokers could be quite different from those in nonsmokers. PMID:22505904

Three-dimensional modeling of oxidized-LDL accumulation and HDL mass transport in a coronary artery: a proof-of-concept study for predicting the region of atherosclerotic plaque development.

PubMed

Sakellarios, Antonis I; Siogkas, Panagiotis K; Athanasiou, Lambros S; Exarchos, Themis P; Papafaklis, Michail I; Bourantas, Christos V; Naka, Katerina K; Michalis, Lampros K; Filipovic, Nenad; Parodi, Oberdan; Fotiadis, Dimitrios I

2013-01-01

Low density lipoprotein (LDL) has a significant role on the atherosclerotic plaque development, while the concentration of high density lipoproteins (HDL) is considered to play an atheroprotective role according to several biochemical mechanisms. In this work, it is the first time that both LDL and HDL concentrations are taken into account in order to predict the regions prone for plaque development. Our modeling approach is based on the use of a realistic three-dimensional reconstructed pig coronary artery in two time points. Biochemical data measured in the pig were also included in order to develop a more customized model. We modeled coronary blood flow by solving the Navier-Stokes equations in the arterial lumen and plasma filtration in the arterial wall using Darcy's Law. HDL transport was modeled only in the arterial lumen using the convection-diffusion equation, while LDL transport was modeled both in the lumen and the arterial wall. An additional novelty of this work is that we model the oxidation of LDL taking into account the atheroprotective role of HDL. The results of our model were in good agreement with histological findings demonstrating that increased oxidized LDL is found near regions of advanced plaques, while non-oxidized LDL is found in regions of early plaque types.

Macrophage activation by heparanase is mediated by TLR-2 and TLR-4 and associates with plaque progression.

PubMed

Blich, Miry; Golan, Amnon; Arvatz, Gil; Sebbag, Anat; Shafat, Itay; Sabo, Edmond; Cohen-Kaplan, Victoria; Petcherski, Sirouch; Avniel-Polak, Shani; Eitan, Amnon; Hammerman, Haim; Aronson, Doron; Axelman, Elena; Ilan, Neta; Nussbaum, Gabriel; Vlodavsky, Israel

2013-02-01

Factors and mechanisms that activate macrophages in atherosclerotic plaques are incompletely understood. We examined the capacity of heparanase to activate macrophages. Highly purified heparanase was added to mouse peritoneal macrophages and macrophage-like J774 cells, and the levels of tumor necrosis factor-α, matrix metalloproteinase-9, interlukin-1, and monocyte chemotactic protein-1 were evaluated by ELISA. Gene expression was determined by RT-PCR. Cells collected from Toll-like receptor-2 and Toll-like receptor-4 knockout mice were evaluated similarly. Heparanase levels in the plasma of patients with acute myocardial infarction, stable angina, and healthy subjects were determined by ELISA. Immunohistochemistry was applied to detect the expression of heparanase in control specimens and specimens of patients with stable angina or acute myocardial infarction. Addition or overexpression of heparanase variants resulted in marked increase in tumor necrosis factor-α, matrix metalloproteinase-9, interlukin-1, and monocyte chemotactic protein-1 levels. Mouse peritoneal macrophages harvested from Toll-like receptor-2 or Toll-like receptor-4 knockout mice were not activated by heparanase. Plasma heparanase level was higher in patients with acute myocardial infarction, compared with patients with stable angina and healthy subjects. Pathologic coronary specimens obtained from vulnerable plaques showed increased heparanase staining compared with specimens of stable plaque and controls. Heparanase activates macrophages, resulting in marked induction of cytokine expression associated with plaque progression toward vulnerability.

A (Sub)Micro-Scale Investigation of Fe Plaque Distribution in Selected Wetland Plant Root Epidermis

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

Feng, Huan

This study focuses on investigation of the distribution of Fe plaque in the root epidermis of the selected wetland plant species (Phragmites australis, Typha latifolia and Spartina alterniflora) using synchrotron X-ray microfluoresces, X-ray absorption near edge structure and transmission X-ray microscope techniques with (sub)micro-scale resolution. The wetland plants were collected in Liberty State Park, New Jersey, USA, and Yangtze River intertidal zone, Shanghai, China, respectively, during the different time period. Although a number of early studies have reported that Fe-oxides can precipitate on the surface of aquatic plants in the rhizosphere to form iron plaque, the role of Fe plaquemore » in regulating metal biogeochemical cycle has been in discussion for decades. The results from this study show that Fe is mainly distributed in the epidermis non-uniformly, and the major Fe species is ferric Fe (Fe3+). This information is needed to make broad inferences about the relevant plant metal uptake mechanisms because Fe accumulation and distribution in the root system is important to understanding the metal transport processes that control the mobility of metals in plants. This study improves our understanding of Fe plaque distributions and speciation in the wetland plant root system, and helps us to understand the function of Fe plaque in metal transport and accumulation through the root system.« less

Visualizing the effect of dynamin inhibition on annular gap vesicle formation and fission

PubMed Central

Nickel, Beth; Boller, Marie; Schneider, Kimberly; Shakespeare, Teresa; Gay, Vernon; Murray, Sandra A.

2013-01-01

Summary Although gap junction plaque assembly has been extensively studied, mechanisms involved in plaque disassembly are not well understood. Disassembly involves an internalization process in which annular gap junction vesicles are formed. These vesicles undergo fission, but the molecular machinery needed for these fissions has not been described. The mechanoenzyme dynamin has been previously demonstrated to play a role in gap junction plaque internalization. To investigate the role of dynamin in annular gap junction vesicle fission, immunocytochemical, time-lapse and transmission electron microscopy were used to analyze SW-13 adrenocortical cells in culture. Dynamin was demonstrated to colocalize with gap junction plaques and vesicles. Dynamin inhibition, by siRNA knockdown or treatment with the dynamin GTPase inhibitor dynasore, increased the number and size of gap junction ‘buds’ suspended from the gap junction plaques. Buds, in control populations, were frequently released to form annular gap junction vesicles. In dynamin-inhibited populations, the buds were larger and infrequently released and thus fewer annular gap junction vesicles were formed. In addition, the number of annular gap junction vesicle fissions per hour was reduced in the dynamin-inhibited populations. We believe this to be the first report addressing the details of annular gap junction vesicle fissions and demonstrating a role of dynamin in this process. This information is crucial for elucidating the relationship between gap junctions, membrane regulation and cell behavior. PMID:23591819

Visualizing the effect of dynamin inhibition on annular gap vesicle formation and fission.

PubMed

Nickel, Beth; Boller, Marie; Schneider, Kimberly; Shakespeare, Teresa; Gay, Vernon; Murray, Sandra A

2013-06-15

Although gap junction plaque assembly has been extensively studied, mechanisms involved in plaque disassembly are not well understood. Disassembly involves an internalization process in which annular gap junction vesicles are formed. These vesicles undergo fission, but the molecular machinery needed for these fissions has not been described. The mechanoenzyme dynamin has been previously demonstrated to play a role in gap junction plaque internalization. To investigate the role of dynamin in annular gap junction vesicle fission, immunocytochemical, time-lapse and transmission electron microscopy were used to analyze SW-13 adrenocortical cells in culture. Dynamin was demonstrated to colocalize with gap junction plaques and vesicles. Dynamin inhibition, by siRNA knockdown or treatment with the dynamin GTPase inhibitor dynasore, increased the number and size of gap junction 'buds' suspended from the gap junction plaques. Buds, in control populations, were frequently released to form annular gap junction vesicles. In dynamin-inhibited populations, the buds were larger and infrequently released and thus fewer annular gap junction vesicles were formed. In addition, the number of annular gap junction vesicle fissions per hour was reduced in the dynamin-inhibited populations. We believe this to be the first report addressing the details of annular gap junction vesicle fissions and demonstrating a role of dynamin in this process. This information is crucial for elucidating the relationship between gap junctions, membrane regulation and cell behavior.

Asymptomatic carotid stenosis is associated with cognitive impairment.

PubMed

Lal, Brajesh K; Dux, Moira C; Sikdar, Siddhartha; Goldstein, Carly; Khan, Amir A; Yokemick, John; Zhao, Limin

2017-10-01

Cerebrovascular risk factors (eg, hypertension, coronary artery disease) and stroke can lead to vascular cognitive impairment. The Asymptomatic Carotid Stenosis and Cognitive Function study evaluated the isolated impact of asymptomatic carotid stenosis (no prior ipsilateral or contralateral stroke or transient ischemic attack) on cognitive function. Cerebrovascular hemodynamic and carotid plaque characteristics were analyzed to elucidate potential mechanisms affecting cognition. There were 82 patients with ≥50% asymptomatic carotid stenosis and 62 controls without stenosis but matched for vascular comorbidities who underwent neurologic, National Institutes of Health Stroke Scale, and comprehensive neuropsychological examination. Overall cognitive function and five domain-specific scores were computed. Duplex ultrasound with Doppler waveform and B-mode imaging defined the degree of stenosis, least luminal diameter, plaque area, and plaque gray-scale median. Breath-holding index (BHI) and microembolization were measured using transcranial Doppler. We assessed cognitive differences between stenosis patients and control patients and of stenosis patients with low vs high BHI and correlated cognitive function with microembolic counts and plaque characteristics. Stenosis and control patients did not differ in vascular risk factors, education, estimated intelligence, or depressive symptoms. Stenosis patients had worse composite cognitive scores (P = .02; Cohen's d = 0.43) and domain-specific scores for learning/memory (P = .02; d = 0.42) and motor/processing speed (P = .01; d = 0.65), whereas scores for executive function were numerically lower (P = .08). Approximately 49.4% of all stenosis patients were impaired in at least two cognitive domains. Precisely 50% of stenosis patients demonstrated a reduced BHI. Stenosis patients with reduced BHI performed worse on the overall composite cognitive score (t = -2.1; P = .02; d = 0.53) and tests for learning/memory (t = -2.7; P = .01; d = 0.66). Cognitive function did not correlate with measures of plaque burden (degree of stenosis, least luminal diameter, and plaque area) or with plaque gray-scale median. Asymptomatic carotid stenosis is associated with cognitive impairment independent of known vascular risk factors for vascular cognitive impairment. Approximately 49.4% of these patients demonstrate impairment in at least two neuropsychological domains. The deficit is driven primarily by reduced motor/processing speed and learning/memory and is mild to moderate in severity. The mechanism for impairment is likely to be hemodynamic as evidenced by reduced cerebrovascular reserve and the likely result of hypoperfusion from a pressure drop across the stenosis in the presence of inadequate collateralization. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Comparative analysis of the electroencephalogram in patients with Alzheimer's disease, diffuse axonal injury patients and healthy controls using LORETA analysis.

PubMed

Ianof, Jéssica Natuline; Fraga, Francisco José; Ferreira, Leonardo Alves; Ramos, Renato Teodoro; Demario, José Luiz Carlos; Baratho, Regina; Basile, Luís Fernando Hindi; Nitrini, Ricardo; Anghinah, Renato

2017-01-01

Alzheimer's disease (AD) is a dementia that affects a large contingent of the elderly population characterized by the presence of neurofibrillary tangles and senile plaques. Traumatic brain injury (TBI) is a non-degenerative injury caused by an external mechanical force. One of the main causes of TBI is diffuse axonal injury (DAI), promoted by acceleration-deceleration mechanisms. To understand the electroencephalographic differences in functional mechanisms between AD and DAI groups. The study included 20 subjects with AD, 19 with DAI and 17 healthy adults submitted to high resolution EEG with 128 channels. Cortical sources of EEG rhythms were estimated by exact low-resolution electromagnetic tomography (eLORETA) analysis. The eLORETA analysis showed that, in comparison to the control (CTL) group, the AD group had increased theta activity in the parietal and frontal lobes and decreased alpha 2 activity in the parietal, frontal, limbic and occipital lobes. In comparison to the CTL group, the DAI group had increased theta activity in the limbic, occipital sublobar and temporal areas. The results suggest that individuals with AD and DAI have impairment of electrical activity in areas important for memory and learning.

Urease activity as a risk factor for caries development in children during a three-year study period: a survival analysis approach

PubMed Central

Morou-Bermudez, E; Elias-Boneta, A; Billings, RJ; Burne, RA; Garcia-Rivas, V; Brignoni-Nazario, V; Suárez-Pérez, E

2011-01-01

Recent cross-sectional studies suggest that reduced ability to generate alkali via the urease pathway in dental plaque may be an important caries risk factor, but it has not been assessed prospectively. OBJECTIVE To evaluate the effect of plaque and saliva urease activity on the risk for developing new caries over a three-year period in children. METHODS A panel of 80 children, three to six years of age at recruitment, was followed prospectively for three years. Plaque urease activity, saliva urease activity and dental caries were measured every six months. Survival analysis methodology was used to evaluate the effect of urease on caries development during the study period adjusted for gender, age, baseline caries levels, sugar consumption, amount of plaque, and mutans streptococci levels. RESULTS The risk for developing new caries increased in a dose-responsive manner with increasing levels of urease activity in saliva (adjusted HRQ4 vs. Q1: 4.98; 95%CI: 1.33, 18.69) and with decreasing urease activity in plaque (adjusted HRQ4 vs. Q1: 0.29; 95%CI: 0.11, 0.76). Multiple measurements of urease activity were conducted to overcome the variability of urease activity in this study. Baseline caries and mutans streptococci in saliva were also important predictors of caries risk. CONCLUSIONS Increased urease activity in saliva can be an indicator of increased caries risk in children, while increased urease activity in plaque may be associated with reduced caries risk. The reproducibility of urease measurements must be improved before these findings can be further tested and clinically applied. PMID:21784411

Autophagy is required for endothelial cell alignment and atheroprotection under physiological blood flow

PubMed Central

Vion, Anne-Clemence; Hammoutene, Adel; Poisson, Johanne; Lasselin, Juliette; Devue, Cecile; Pic, Isabelle; Dupont, Nicolas; Busse, Johanna; Stark, Konstantin; Lafaurie-Janvore, Julie; Barakat, Abdul I.; Loyer, Xavier; Souyri, Michele; Viollet, Benoit; Julia, Pierre; Tedgui, Alain; Codogno, Patrice; Rautou, Pierre-Emmanuel

2017-01-01

It has been known for some time that atherosclerotic lesions preferentially develop in areas exposed to low SS and are characterized by a proinflammatory, apoptotic, and senescent endothelial phenotype. Conversely, areas exposed to high SS are protected from plaque development, but the mechanisms have remained elusive. Autophagy is a protective mechanism that allows recycling of defective organelles and proteins to maintain cellular homeostasis. We aimed to understand the role of endothelial autophagy in the atheroprotective effect of high SS. Atheroprotective high SS stimulated endothelial autophagic flux in human and murine arteries. On the contrary, endothelial cells exposed to atheroprone low SS were characterized by inefficient autophagy as a result of mammalian target of rapamycin (mTOR) activation, AMPKα inhibition, and blockade of the autophagic flux. In hypercholesterolemic mice, deficiency in endothelial autophagy increased plaque burden only in the atheroresistant areas exposed to high SS; plaque size was unchanged in atheroprone areas, in which endothelial autophagy flux is already blocked. In cultured cells and in transgenic mice, deficiency in endothelial autophagy was characterized by defects in endothelial alignment with flow direction, a hallmark of endothelial cell health. This effect was associated with an increase in endothelial apoptosis and senescence in high-SS regions. Deficiency in endothelial autophagy also increased TNF-α–induced inflammation under high-SS conditions and decreased expression of the antiinflammatory factor KLF-2. Altogether, these results show that adequate endothelial autophagic flux under high SS limits atherosclerotic plaque formation by preventing endothelial apoptosis, senescence, and inflammation. PMID:28973855

Intracellular high cholesterol content disorders the clock genes, apoptosis-related genes and fibrinolytic-related genes rhythmic expressions in human plaque-derived vascular smooth muscle cells.

PubMed

Lin, Changpo; Tang, Xiao; Xu, Lirong; Qian, Ruizhe; Shi, Zhenyu; Wang, Lixin; Cai, Tingting; Yan, Dong; Fu, Weiguo; Guo, Daqiao

2017-07-10

The clock genes are involved in regulating cardiovascular functions, and their expression disorders would lead to circadian rhythm disruptions of clock-controlled genes (CCGs), resulting in atherosclerotic plaque formation and rupture. Our previous study revealed the rhythmic expression of clock genes were attenuated in human plaque-derived vascular smooth muscle cells (PVSMCs), but failed to detect the downstream CCGs expressions and the underlying molecular mechanism. In this study, we examined the difference of CCGs rhythmic expression between human normal carotid VSMCs (NVSMCs) and PVSMCs. Furthermore, we compared the cholesterol and triglycerides levels between two groups and the link to clock genes and CCGs expressions. Seven health donors' normal carotids and 19 carotid plaques yielded viable cultured NVSMCs and PVSMCs. The expression levels of target genes were measured by quantitative real-time PCR and Western-blot. The intracellular cholesterol and triglycerides levels were measured by kits. The circadian expressions of apoptosis-related genes and fibrinolytic-related genes were disordered. Besides, the cholesterol levels were significant higher in PVSMCs. After treated with cholesterol or oxidized low density lipoprotein (ox-LDL), the expressions of clock genes were inhibited; and the rhythmic expressions of clock genes, apoptosis-related genes and fibrinolytic-related genes were disturbed in NVSMCs, which were similar to PVSMCs. The results suggested that intracellular high cholesterol content of PVSMCs would lead to the disorders of clock genes and CCGs rhythmic expressions. And further studies should be conducted to demonstrate the specific molecular mechanisms involved.

Studies of protein aggregation in A53T α-synuclein transgenic, Tg2576 transgenic, and P246L presenilin-1 knock-in cross bred mice.

PubMed

Emmer, Kristel L; Covy, Jason P; Giasson, Benoit I

2012-01-24

Synucleinopathies are a group of neurodegenerative disorders, including Parkinson disease, associated with neuronal amyloid inclusions comprised of the presynaptic protein α-synuclein (α-syn); however the biological events that initiate and lead to the formation of these inclusions are still poorly understood. There is mounting evidence that intracellular α-syn aggregation may proceed via a seeding mechanism and could spread between neurons through a prion-like mechanism that may involve other amyloidogenic proteins. Several lines of evidence suggest that Aβ peptides and/or extracellular Aβ deposits may directly or indirectly promote intracellular α-syn aggregation. To assess the effects of Aβ peptides and extracellular Aβ deposits on α-syn aggregate formation, transgenic mice (line M83) expressing A53T human α-syn that are sensitive to developing α-syn pathological inclusions were cross bred to Tg2576 transgenic mice that generated elevated levels of Aβ peptides and develop abundant Aβ plaques. In addition these mice were bred to mice with the P264L presenilin-1 knock-in mutation that further promotes Aβ plaque formation. These mice demonstrated the expected formation of Aβ plaques; however despite the accumulation of hyperphosphorylated α-syn dystrophic neurites within or surrounding Aβ plaques, no additional α-syn pathologies were observed. These studies show that Aβ amyloid deposits can cause the local aggregation of α-syn, but these did not lead to more extensive α-syn pathology. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Rice bran enzymatic extract reduces atherosclerotic plaque development and steatosis in high-fat fed ApoE-/- mice.

PubMed

Perez-Ternero, Cristina; Claro, Carmen; Parrado, Juan; Herrera, Maria Dolores; Alvarez de Sotomayor, Maria

2017-05-01

Rice bran is a by-product of rice milling and is rich in bioactive molecules such as γ-oryzanol, phytosterols, and tocotrienols. The rice bran enzymatic extract (RBEE) previously showed vessel remodeling prevention and lipid-lowering, antioxidant, anti-inflammatory, and antiapoptotic activities. The aim of this study was to identify RBEE hypolipidemic mechanisms and to study the effects of RBEE on the progression of atherosclerosis disease and linked vascular dysfunction and liver steatosis in apolipoprotein E-knockout (ApoE-/-) mice fed low- or high-fat (LFD, HFD, respectively) and cholesterol diets. ApoE-/- mice were fed LFD (13% kcal) or HFD (42% kcal) supplemented or not supplemented with 1 or 5% RBEE (w/w) for 23 wk. Then, serum, aorta, liver, and feces were collected and flash frozen for further analysis. RBEE supplementation of HFD improved serum values by augmenting high-density lipoprotein cholesterol and preventing total cholesterol and aspartate aminotransferase increase. 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity was attenuated (1 and 5% RBEE) and cholesterol excretion increased (5% RBEE). Diet supplementation with 5% RBEE reduced plaque development regardless of the diet. In HFD-fed mice, both doses of RBEE reduced lipid deposition and macrophage infiltration in the aortic sinus and downregulated intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression. None of these effects was observed in mice fed LFD. Liver steatosis was reduced by RBEE supplementation of LFD (1% RBEE) and HFD (1 and 5% RBEE) and nuclear peroxisome proliferator-activated receptor-α expression upregulated in the HDF 5% RBEE group. Regular consumption of RBEE-supplemented HFD reduced plaque development and liver steatosis by decreasing inflammation and hyperlipidemia through an HMG-CoA reductase activity and lipid excretion-related mechanism. Copyright © 2016 Elsevier Inc. All rights reserved.

Incremental Value of Plaque Enhancement in Patients with Moderate or Severe Basilar Artery Stenosis: 3.0 T High-Resolution Magnetic Resonance Study.

PubMed

Wang, Wanqian; Yang, Qi; Li, Debiao; Fan, Zhaoyang; Bi, Xiaoming; Du, Xiangying; Wu, Fang; Wu, Ye; Li, Kuncheng

2017-01-01

To investigate the clinical relevance of plaque's morphological characteristics and distribution pattern using 3.0 T high-resolution magnetic resonance imaging (HRMRI) in patients with moderate or severe basilar artery (BA) atherosclerosis stenosis. Fifty-seven patients (33 symptomatic patients and 24 asymptomatic patients) were recruited for 3.0 T HRMRI scan; all of them had >50% stenosis on the BA. The intraplaque hemorrhage (IPH), contrast-enhancement pattern, and distribution of BA plaques were compared between the symptomatic and asymptomatic groups. Factors potentially associated with posterior ischemic stroke were calculated by multivariate analyses. Enhancement of BA plaque was more frequently observed in symptomatic than in asymptomatic patients (27/33, 81.8% versus 11/24, 45.8%; p < 0.01). In multivariate regression analysis, plaque enhancement (OR = 7.193; 95% CI: 1.880-27.517; p = 0.004) and smoking (OR = 4.402; 95% CI: 2.218-15.909; p = 0.024) were found to be independent risk factors of posterior ischemic events in patients with BA stenosis >50%. Plaques were mainly distributed at the ventral site (39.3%) or involved more than two arcs (21.2%) in the symptomatic group but were mainly distributed at left (33.3%) and right (25.0%) sites in the asymptomatic group.

Prevalence of Helicobacter pylori in the adolescent oral cavity: dependence on orthodontic therapy, oral flora and hygiene.

PubMed

Wichelhaus, Andrea; Brauchli, Lorenz; Song, Qunsheng; Adler, Guido; Bode, Günter

2011-07-01

Helicobacter pylori (HP) infection usually occurs in childhood. While there are various studies on the prevalence of HP in dental plaque, ours is the first to analyze its prevalence during orthodontic therapy and its interaction with competitive bacteria in adolescents. The prevalence of HP was examined before and during the first 12 weeks of orthodontic therapy with fixed appliances in 11 patients with a mean age of 12.7 years. A total of 93 plaque samples were analyzed using PCR. The data acquired at every consultation were the following: PCR analysis of dental plaque and (13)C urea breath tests for HP, quantitative analyses of saliva for Lactobacilli and Streptococcus mutans, the interproximal plaque index (API), and sulcus bleeding index (SBI). The prevalence of HP in plaque was 82% before orthodontic therapy, dropping to 54% during therapy (t test, p≤0.05). In contrast to HP's prevalence, the Lactobacilli count rose (p≤0.05). The number of Streptococcus mutans bacteria in saliva decreased during orthodontic therapy (p≤0.05). The prevalence of HP in dental plaque amounted to 82%. Orthodontic treatment did not reduce its prevalence. The prevalence of Lactobacilli was inversely proportional to that of HP.

Polarization properties of amyloid-beta plaques in Alzheimer's disease (Conference Presentation)

NASA Astrophysics Data System (ADS)

Baumann, Bernhard; Wöhrer, Adelheid; Ricken, Gerda; Pircher, Michael; Kovacs, Gabor G.; Hitzenberger, Christoph K.

2016-03-01

In histopathological practice, birefringence is used for the identification of amyloidosis in numerous tissues. Amyloid birefringence is caused by the parallel arrangement of fibrous protein aggregates. Since neurodegenerative processes in Alzheimer's disease (AD) are also linked to the formation of amyloid-beta (Aβ) plaques, optical methods sensitive to birefringence may act as non-invasive tools for Aβ identification. At last year's Photonics West, we demonstrated polarization-sensitive optical coherence tomography (PS-OCT) imaging of ex vivo cerebral tissue of advanced stage AD patients. PS-OCT provides volumetric, structural imaging based on both backscatter contrast and tissue polarization properties. In this presentation, we report on polarization-sensitive neuroimaging along with numerical simulations of three-dimensional Aβ plaques. High speed PS-OCT imaging was performed using a spectral domain approach based on polarization maintaining fiber optics. The sample beam was interfaced to a confocal scanning microscope arrangement. Formalin-fixed tissue samples as well as thin histological sections were imaged. For comparison to the PS-OCT results, ray propagation through plaques was modeled using Jones analysis and various illumination geometries and plaque sizes. Characteristic polarization patterns were found. The results of this study may not only help to understand PS-OCT imaging of neuritic Aβ plaques but may also have implications for polarization-sensitive imaging of other fibrillary structures.

Assessment of salivary and plaque pH and oral health status among children with and without intellectual disabilities.

PubMed

Radha, G; Swathi, V; Jha, Abhishek

2016-01-01

This study explores the association of disabilities and oral health. The aim of the study was to assess the salivary and plaque pH and oral health status of children with and without disabilities. A total of 100 schoolchildren (50 with disabilities and 50 without disabilities) were examined from 9 to 15 years age group. Saliva and plaque pH analysis were done to both the groups. Clinical data were collected on periodontal status, dental caries using WHO criteria. pH values of different groups, difference between the means were calculated using independent t-test, and frequency distribution was analyzed using Chi-square test. Statistical significance, P value was set at 0.05. Mean plaque and salivary pH scores were lesser (5.73 and 5.67) in children with intellectual disabilities (IDs) (P< 0.001). Subjects with disabilities had also statistically significant higher CPI scores and decayed, missing, and filled scores than their healthy counterparts (P< 0.001). There is a statistically significant difference in plaque and salivary pH among children with and without ID with lower plaque and salivary pH among children with ID. In addition to this, the oral health was also more compromised in children with ID, which confirms a need for preventive treatment for these children.

Association between increased epicardial adipose tissue volume and coronary plaque composition.

PubMed

Yamashita, Kennosuke; Yamamoto, Myong Hwa; Ebara, Seitarou; Okabe, Toshitaka; Saito, Shigeo; Hoshimoto, Koichi; Yakushiji, Tadayuki; Isomura, Naoei; Araki, Hiroshi; Obara, Chiaki; Ochiai, Masahiko

2014-09-01

To assess the relationship between epicardial adipose tissue volume (EATV) and plaque vulnerability in significant coronary stenosis using a 40-MHz intravascular ultrasound (IVUS) imaging system (iMap-IVUS), we analyzed 130 consecutive patients with coronary stenosis who underwent dual-source computed tomography (CT) and cardiac catheterization. Culprit lesions were imaged by iMap-IVUS before stenting. The iMAP-IVUS system classified coronary plaque components as fibrous, lipid, necrotic, or calcified tissue, based on the radiofrequency spectrum. Epicardial adipose tissue was measured as the tissue ranging from -190 to -30 Hounsfield units. EATV, calculated as the sum of the fat areas on short-axis images, was 85.0 ± 34.0 cm(3). There was a positive correlation between EATV and the percentage of necrotic plaque tissue (R (2) = 0.34, P < 0.01), while there was a negative correlation between EATV and the percentage of fibrous tissue (R (2) = 0.24, P < 0.01). Multivariate analysis revealed that an increased low-density lipoprotein cholesterol level (β = 0.15, P = 0.03) and EATV (β = 0.14, P = 0.02) were independently associated with the percentage of necrotic plaque tissue. An increase in EATV was associated with the development of coronary atherosclerosis and, potentially, with the most dangerous type of plaque.

The sleep–wake cycle and Alzheimer’s disease: what do we know?

PubMed Central

Lim, Miranda M.; Gerstner, Jason R.; Holtzman, David M.

2014-01-01

SUMMARY Sleep–wake disturbances are a highly prevalent and often disabling feature of Alzheimer’s disease (AD). A cardinal feature of AD includes the formation of amyloid plaques, associated with the extracellular accumulation of the amyloid-β (Aβ) peptide. Evidence from animal and human studies suggests that Aβ pathology may disrupt the sleep–wake cycle, in that as Aβ accumulates, more sleep–wake fragmentation develops. Furthermore, recent research in animal and human studies suggests that the sleep–wake cycle itself may influence Alzheimer’s disease onset and progression. Chronic sleep deprivation increases amyloid plaque deposition, and sleep extension results in fewer plaques in experimental models. In this review geared towards the practicing clinician, we discuss possible mechanisms underlying the reciprocal relationship between the sleep–wake cycle and AD pathology and behavior, and present current approaches to therapy for sleep disorders in AD. PMID:25405649

Application of the laguerre deconvolution method for time-resolved fluorescence spectroscopy to the characterization of atherosclerotic plaques.

PubMed

Jo, J A; Fang, Q; Papaioannou, T; Qiao, J H; Fishbein, M C; Beseth, B; Dorafshar, A H; Reil, T; Baker, D; Freischlag, J; Marcu, L

2005-01-01

This study investigates the ability of time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) to detect inflammation in atherosclerotic lesion, a key feature of plaque vulnerability. A total of 348 TR-LIFS measurements were taken from carotid plaques of 30 patients, and subsequently analyzed using the Laguerre deconvolution technique. The investigated spots were classified as Early, Fibrotic/Calcified or Inflamed lesions. A stepwise linear discriminant analysis algorithm was developed using spectral and TR features (normalized intensity values and Laguerre expansion coefficients at discrete emission wavelengths, respectively). Features from only three emission wavelengths (390, 450 and 500 nm) were used in the classifier. The Inflamed lesions were discriminated with sensitivity > 80% and specificity > 90 %, when the Laguerre expansion coefficients were included in the feature space. These results indicate that TR-LIFS information derived from the Laguerre expansion coefficients at few selected emission wavelengths can discriminate inflammation in atherosclerotic plaques. We believe that TR-LIFS derived Laguerre expansion coefficients can provide a valuable additional dimension for the detection of vulnerable plaques.

Prevalence of noncalcified coronary plaque in patients with calcium score of 0: the silent enemy.

PubMed

Koulaouzidis, George; Charisopoulou, Dafni; Jenkins, Paul J; Koulaouzidis, Anastasios; McArthur, Tony

2013-04-01

Noncalcified coronary artery plaques (NCAPs) are susceptible to rupture, resulting in coronary artery thrombosis. Using computer tomography coronary angiography (CTCA), we evaluated the prevalence and degree of stenosis caused by NCAP in patients without coronary artery calcification (CAC). A retrospective analysis of 447 symptomatic patients with 0 CAC score revealed negative CTCA in 400 (89.5%). Noncalcified coronary artery plaques were demonstrated in 47 (10.5%), with 4 presenting stenosis >50%. Patients with positive CTCA, compared to those with normal CTCA, had significantly higher mean age (56.2 years vs 50.6 years, P < .004) and higher pretest coronary artery disease (CAD) probability (26% vs 34%, P < .0001). Noncalcified coronary artery plaque was predominantly developed in the proximal segment of the left anterior descending artery. Noncalcified coronary artery plaque is present in up to 10% of patients with a CAC score of 0. Computer tomography coronary angiography could be of diagnostic value in symptomatic patients with multiple risk factors for CAD, even in the absence of CAC.

The Lipid-Rich Plaque Study of vulnerable plaques and vulnerable patients: Study design and rationale.

PubMed

Waksman, Ron; Torguson, Rebecca; Spad, Mia-Ashley; Garcia-Garcia, Hector; Ware, James; Wang, Rui; Madden, Sean; Shah, Priti; Muller, James

2017-10-01

It has been hypothesized that the outcome post-PCI could be improved by the detection and subsequent treatment of vulnerable patients and lipid-rich vulnerable coronary plaques (LRP). A near-infrared spectroscopy (NIRS) catheter capable of detecting LRP is being evaluated in The Lipid-Rich Plaque Study. The LRP Study is an international, multicenter, prospective cohort study conducted in patients with suspected coronary artery disease (CAD) who underwent cardiac catheterization with possible ad hoc PCI for an index event. Patient level and plaque level events were detected by follow-up in the subsequent 2 years. Enrollment began in February 2014 and was completed in March 2016; a total of 1,562 patients were enrolled. Adjudication of new coronary event occurrence and de novo culprit lesion location during the 2-year follow-up is performed by an independent clinical end-points committee (CEC) blinded to NIRS-IVUS findings. The first analysis of the results will be performed when at least 20 de novo events have occurred for which follow-up angiographic data and baseline NIRS-IVUS measurements are available. It is expected that results of the study will be announced in 2018. The LRP Study will test the hypotheses that NIRS-IVUS imaging to detect LRP in patients can identify vulnerable patients and vulnerable plaques. Identification of vulnerable patients will assist future studies of novel systemic therapies; identification of localized vulnerable plaques would enhance future studies of possible preventive measures. Copyright © 2017 Elsevier Inc. All rights reserved.

Design and Synthesis of Gold Nanoparticle Contrast Agents for Atherosclerosis Imaging with Computed tomography

NASA Astrophysics Data System (ADS)

Chhour, Peter

Cell tracking offers the opportunity to study migration and localization of cells in vivo, allowing investigations of disease mechanisms and drug efficacy. Monocytes play a key role in the progression of atherosclerotic plaques in the coronary arteries. While x-ray computed tomography (CT) is commonly used to clinically assess coronary plaque burden, cell tracking with CT is mostly unexplored. The establishment of monocyte cell tracking tools would allow for the direct investigation of gene and drug therapies aimed at monocyte recruitment in atherosclerosis. In this thesis, we present the design and optimization of gold nanoparticles as CT contrast agents for cell tracking of monocyte recruitment to atherosclerotic plaques. Gold nanoparticle polymer constructs with controlled localization are evaluated as potential monocyte labels. However, cytotoxic effects were observed at concentrations necessary for cell labeling. Therefore, variations in physical and chemical properties of gold nanoparticles were explored as cell labels for monocyte tracking. Each formulation was screened for effects on cell viability, cell function and uptake in monocytes. The uptake in monocytes revealed a complex relationship with nanoparticle size behavior dependent on the surface ligand used. This led to the selection of an optimal size and coating for monocyte labeling, 11-mercaptoundecanoic acid coated 15 nm gold nanoparticles. This formulation was further investigated for cell viability, function, and uptake with isolated primary monocytes. Moreover, primary monocytes labeled with this formulation were used to observe monocyte recruitment in atherosclerotic mice. Mice with early atherosclerotic plaques received intravenously injections of gold labeled monocytes and their recruitment to plaques were observed over 5 days with CT. Increases in CT attenuation in the plaque and transmission electron microscopy of plaque sections indicated the presence of gold labeled monocytes in the plaque. These results demonstrate the feasibility of using CT to track ex-vivo labeled cells non-invasively with CT and could further be used to investigate drugs aimed at modulating monocyte recruitment in the treatment of atherosclerosis. This work expands the applications of cell tracking and may lead to additional uses in other diseases.

The effectiveness of a magnetized water oral irrigator (Hydro Floss) on plaque, calculus and gingival health.

PubMed

Johnson, K E; Sanders, J J; Gellin, R G; Palesch, Y Y

1998-04-01

The purpose of this study was to evaluate the effects of a magnetized water oral irrigator on plaque, calculus and gingival health. 29 patients completed this double-blind crossover study. Each patient was brought to baseline via an oral prophylaxis with a plaque index < or = 1 and a gingival index < or = 1. Subjects used the irrigator for a period of 3 months with the magnet and 3 months without the magnet. After each 3 month interval, data were collected using the plaque index, gingival index, and accretions index. The repeated measures analysis on plaque, gingival and calculus indices yielded a statistically-significant period effect for PlI (p=0.0343), GI (p=0.0091), and approached significance for calculus (p=0.0593). This meant that the effect of irrigation resulted in a decrease of all indices over time. Therefore, the treatment effect on each index was evaluated using only the measurements obtained at the end of the first period (i.e., assuming a parallel design). Irrigation with magnetized water resulted in 64% less calculus compared to the control group. The reduction was statistically significant (p< or =0.02). The reduction by 27% in gingival index was not statistically significant. The reduction in plaque was minimal (2.2%). A strong positive correlation between the plaque index and the Watt accretion index was observed. The magnetized water oral irrigator could be a useful adjunct in the prevention of calculus accumulation in periodontal patients, but appears to have minimal effect on plaque reduction. The results indicated a clinical improvement in the gingival index, but this was not a statistically significant finding.

Aspirin inhibits human telomerase activation in unstable carotid plaques

PubMed Central

LI, FANGMING; GUO, YI; JIANG, XIN; ZHONG, JIANXIN; LI, GUANDONG; SUN, SHENGGANG

2013-01-01

The activation of telomerase in unstable plaques is an important factor in atherosclerosis, and may be predictive of the risk of cerebrovascular diseases. Human telomerase reverse transcriptase (hTERT) is a subunit of telomerase that is essential for telomerase activation. The aim of the present study was to investigate whether aspirin inhibits the activation of telomerase and hTERT in unstable carotid plaques. Polymorphonuclear neutrophils (PMNs) derived from carotid plaques were isolated from the washing medium of angioplasty balloons, while circulating PMNs, isolated from arterial blood, served as the controls. A polymerase chain reaction-based telomeric repeat amplification protocol (TRAP) enzyme-linked immunosorbent assay (ELISA) was used to measure the telomerase activity in the cells following treatment with aspirin. The mRNA and protein expression of hTERT were detected by a reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis, respectively. The results revealed that the atherosclerotic plaques were positive for telomerase activity, and that aspirin inhibited the telomerase activity of the PMNs derived from the plaques. In addition, aspirin was demonstrated to inhibit the mRNA and protein expression of hTERT through the suppression of hTERT transcriptional activity; however, it had no inhibitory effect on the telomerase activity of the circulating PMNs. Thus, the activation of telomerase in resident PMNs is critical in the instability of carotid plaques. The upregulation of telomerase and hTERT during the progression of atherosclerosis may indicate a role for telomerase in the vascular remodeling that occurs during atherogenesis. Aspirin was demonstrated to inhibit the activation of telomerase via an hTERT-dependent manner in the PMN cells of unstable carotid plaques, and thus hTERT may be considered as a target in the treatment of cerebrovascular diseases. PMID:23935747

Wall-based measurement features provides an improved IVUS coronary artery risk assessment when fused with plaque texture-based features during machine learning paradigm.

PubMed

Banchhor, Sumit K; Londhe, Narendra D; Araki, Tadashi; Saba, Luca; Radeva, Petia; Laird, John R; Suri, Jasjit S

2017-12-01

Planning of percutaneous interventional procedures involves a pre-screening and risk stratification of the coronary artery disease. Current screening tools use stand-alone plaque texture-based features and therefore lack the ability to stratify the risk. This IRB approved study presents a novel strategy for coronary artery disease risk stratification using an amalgamation of IVUS plaque texture-based and wall-based measurement features. Due to common genetic plaque makeup, carotid plaque burden was chosen as a gold standard for risk labels during training-phase of machine learning (ML) paradigm. Cross-validation protocol was adopted to compute the accuracy of the ML framework. A set of 59 plaque texture-based features was padded with six wall-based measurement features to show the improvement in stratification accuracy. The ML system was executed using principle component analysis-based framework for dimensionality reduction and uses support vector machine classifier for training and testing-phases. The ML system produced a stratification accuracy of 91.28%, demonstrating an improvement of 5.69% when wall-based measurement features were combined with plaque texture-based features. The fused system showed an improvement in mean sensitivity, specificity, positive predictive value, and area under the curve by: 6.39%, 4.59%, 3.31% and 5.48%, respectively when compared to the stand-alone system. While meeting the stability criteria of 5%, the ML system also showed a high average feature retaining power and mean reliability of 89.32% and 98.24%, respectively. The ML system showed an improvement in risk stratification accuracy when the wall-based measurement features were fused with the plaque texture-based features. Copyright © 2017 Elsevier Ltd. All rights reserved.

Increase in the adhesion molecule P-selectin in endothelium overlying atherosclerotic plaques. Coexpression with intercellular adhesion molecule-1.

PubMed Central

Johnson-Tidey, R. R.; McGregor, J. L.; Taylor, P. R.; Poston, R. N.

1994-01-01

P-selectin (GMP-140) is an adhesion molecule present within endothelial cells that is rapidly translocated to the cell membrane upon activation, where it mediates endothelial-leukocyte interactions. Immunohistochemical analysis of human atherosclerotic plaques has shown strong expression of P-selectin by the endothelium overlying active atherosclerotic plaques. P-selectin is not, however, detected in normal arterial endothelium or in endothelium overlying inactive fibrous plaques. Color image analysis was used to quantitate the degree of P-selectin expression in the endothelium and demonstrates a statistically significant increase in P-selectin expression by atherosclerotic endothelial cells. Double immunofluorescence shows that some of this P-selectin is expressed on the luminal surface of the endothelial cells. Previous work has demonstrated a significant up-regulation in the expression of the intercellular adhesion molecule-1 in atherosclerotic endothelium and a study on the expression of intercellular adhesion molecule-1 and P-selectin in atherosclerosis shows a highly positive correlation. These results suggest that the selective and cooperative expression of P-selectin and intercellular adhesion molecule-1 may be involved in the recruitment of monocytes into sites of atherosclerosis. Images Figure 1 Figure 3 Figure 4 Figure 5 PMID:7513951

Myocardial Bridge and Acute Plaque Rupture

PubMed Central

Perl, Leor; Daniels, David; Schwartz, Jonathan; Tanaka, Shige; Yeung, Alan; Tremmel, Jennifer A.; Schnittger, Ingela

2016-01-01

A myocardial bridge (MB) is a common anatomic variant, most frequently located in the left anterior descending coronary artery, where a portion of the coronary artery is covered by myocardium. Importantly, MBs are known to result in a proximal atherosclerotic lesion. It has recently been postulated that these lesions predispose patients to acute coronary events, even in cases of otherwise low-risk patients. One such mechanism may involve acute plaque rupture. In this article, we report 2 cases of patients with MBs who presented with acute coronary syndromes despite having low cardiovascular risk. Their presentation was life-risking and both were treated urgently and studied with coronary angiographies and intravascular ultrasound. This latter modality confirmed a rupture of an atherosclerotic plaque proximal to the MB as a likely cause of the acute events. These cases, of unexplained acute coronary syndrome in low-risk patients, raise the question of alternative processes leading to the event and the role MB play as an underlying cause of ruptured plaques. In some cases, an active investigation for this entity may be warranted, due to the prognostic implications of the different therapeutic modalities, should an MB be discovered. PMID:28251167

Adjunctive dental therapy via tooth plaque reduction and gingivitis treatment by blue light-emitting diodes tooth brushing

NASA Astrophysics Data System (ADS)

Genina, Elina A.; Titorenko, Vladimir A.; Belikov, Andrey V.; Bashkatov, Alexey N.; Tuchin, Valery V.

2015-12-01

The efficacy of blue light-emitting toothbrushes (B-LETBs) (405 to 420 nm, power density 2 mW/cm2) for reduction of dental plaques and gingival inflammation has been evaluated. Microbiological study has shown the multifactor therapeutic action of the B-LETBs on oral pathological microflora: in addition to partial mechanical removal of bacteria, photodynamic action suppresses them up to 97.5%. In the pilot clinical studies, subjects with mild to moderate gingivitis have been randomly divided into two groups: a treatment group that used the B-LETBs and a control group that used standard toothbrushes. Indices of plaque, gingival bleeding, and inflammation have been evaluated. A significant improvement of all dental indices in comparison with the baseline (by 59%, 66%, and 82% for plaque, gingival bleeding, and inflammation, respectively) has been found. The treatment group has demonstrated up to 50% improvement relative to the control group. We have proposed the B-LETBs to serve for prevention of gingivitis or as an alternative to conventional antibiotic treatment of this disease due to their effectiveness and the absence of drug side effects and bacterial resistance.

Macrophagic CD146 promotes foam cell formation and retention during atherosclerosis

PubMed Central

Luo, Yongting; Duan, Hongxia; Qian, Yining; Feng, Liqun; Wu, Zhenzhen; Wang, Fei; Feng, Jing; Yang, Dongling; Qin, Zhihai; Yan, Xiyun

2017-01-01

The persistence of cholesterol-engorged macrophages (foam cells) in the artery wall fuels the development of atherosclerosis. However, the mechanism that regulates the formation of macrophage foam cells and impedes their emigration out of inflamed plaques is still elusive. Here, we report that adhesion receptor CD146 controls the formation of macrophage foam cells and their retention within the plaque during atherosclerosis exacerbation. CD146 is expressed on the macrophages in human and mouse atheroma and can be upregulated by oxidized low-density lipoprotein (oxLDL). CD146 triggers macrophage activation by driving the internalization of scavenger receptor CD36 during lipid uptake. In response to oxLDL, macrophages show reduced migratory capacity toward chemokines CCL19 and CCL21; this capacity can be restored by blocking CD146. Genetic deletion of macrophagic CD146 or targeting of CD146 with an antibody result in much less complex plaques in high-fat diet-fed ApoE−/− mice by causing lipid-loaded macrophages to leave plaques. Collectively, our findings identify CD146 as a novel retention signal that traps macrophages within the artery wall, and a promising therapeutic target in atherosclerosis treatment. PMID:28084332

Adjunctive dental therapy via tooth plaque reduction and gingivitis treatment by blue light-emitting diodes tooth brushing.

PubMed

Genina, Elina A; Titorenko, Vladimir A; Belikov, Andrey V; Bashkatov, Alexey N; Tuchin, Valery V

2015-01-01

The efficacy of blue light-emitting toothbrushes (B-LETBs) (405 to 420 nm, power density 2  mW/cm(2)) for reduction of dental plaques and gingival inflammation has been evaluated. Microbiological study has shown the multifactor therapeutic action of the B-LETBs on oral pathological microflora: in addition to partial mechanical removal of bacteria, photodynamic action suppresses them up to 97.5%. In the pilot clinical studies, subjects with mild to moderate gingivitis have been randomly divided into two groups: a treatment group that used the B-LETBs and a control group that used standard toothbrushes. Indices of plaque, gingival bleeding, and inflammation have been evaluated. A significant improvement of all dental indices in comparison with the baseline (by 59%, 66%, and 82% for plaque, gingival bleeding, and inflammation, respectively) has been found. The treatment group has demonstrated up to 50% improvement relative to the control group. We have proposed the B-LETBs to serve for prevention of gingivitis or as an alternative to conventional antibiotic treatment of this disease due to their effectiveness and the absence of drug side effects and bacterial resistance.

The effect of coronary artery plaque composition, morphology and burden on Absorb bioresorbable vascular scaffold expansion and eccentricity - A detailed analysis with optical coherence tomography.

PubMed

Shaw, Elizabeth; Allahwala, Usaid K; Cockburn, James A; Hansen, Thomas C E; Mazhar, Jawad; Figtree, Gemma A; Hansen, Peter S; Bhindi, Ravinay

2015-04-01

Suboptimal stent expansion correlates with adverse cardiac events. There is limited information regarding Absorb bioresorbable vascular scaffold (BVS) expansion characteristics. Optical coherence tomography (OCT) allows for high-resolution assessment of plaque morphology, composition and assessment of BVS expansion. This study evaluates coronary plaque composition, morphology and burden and their effect on Absorb BVS expansion using OCT. Two thousand three hundred and thirty four frames totalling 462.6 mm of BVS from twenty OCT-guided BVS implantations were examined. 200 μm longitudinal cross-sections of each BVS were analysed for lumen contours and plaque characteristics. The relationship between each plaque characteristic and scaffold expansion index (SEI) or scaffold eccentricity index (SEC) was analysed by repeated measures ANOVA. Forty-four fibrous and 265 calcific plaques were identified. Lower SEI was significantly (p<0.001) associated with greater calcific plaque (CP) area (mean SEI 78.9% vs. 80.0%), thickness (78.5% vs. 80.4%) and lower CP depth (78.3% vs. 80.2%). Lower SEC was significantly (p<0.001) associated with greater fibrous plaque (FP) area (0.84 vs. 0.85), thickness (0.83 vs. 0.86), arc angle (0.84 vs. 0.85), greater CP area (0.83 vs. 0.86), CP thickness (0.83 vs. 0.86), CP angle (0.84 vs. 0.85) and lower CP depth (0.84 vs. 0.85). Greater FP area was associated with greater SEI (81.0% vs. 80.0%, p<0.001), even after adjustment for target vessel size. Greater FP angle (80.7% vs 78.3%, p<0.001) and quadrants occupied were also associated (80.0% vs 78.5%, p<0.002) with greater SEI. BVS expansion and eccentricity are significantly impacted by plaque composition, morphology and burden. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

A randomized clinical study comparing the plaque inhibition effect of a SnF2/SHMP dentifrice (blend-a-med EXPERT GUMS PROTECTION) and a chlorhexidine digluconate dentifrice (Lacalut Aktiv).

PubMed

Bellamy, P G; Khera, N; Day, T N; Mussett, A J; Barker, M L

2009-01-01

To compare the plaque inhibition benefits of a control 0.454% stannous fluoride/sodium hexametaphosphate/sodium fluoride dentifrice (SnF2/SHMP with 1450 ppm F) to a chlorhexidine digluconate (0.05%), aluminum lactate (0.8%), and aluminum fluoride (AlF3/Chx with 1400 ppm F) dentifrice. Twenty-nine subjects were randomized to a two-period, two-treatment, double-blind crossover sequence using blend-a-med EXPERT GUMS PROTECTION toothpaste (SnF2/SHMP) and Lacalut Aktiv toothpaste (AlF3/Chx). Each treatment was used along with a standard manual toothbrush (Oral-B P35 Indicator) for 17 days. Digital plaque image analysis (DPIA) was used at the end of each period for three consecutive days to evaluate plaque levels; a) overnight (A.M. pre-brush); b) following 40 seconds of brushing with the test product (A.M. post-brush); and c) mid-afternoon (P.M.). Images were analyzed using an objective computer algorithm to calculate the total area of visible plaque. A four-day washout period was instituted for the crossover phase. Twenty-seven subjects completed the study. The SnF2/SHMP dentifrice provided a statistically significant lower level of plaque area coverage compared to the AlF3/Chx dentifrice at all time points. For the SnF2/SHMP dentifrice, plaque coverage was 19.4% lower (p = 0.0043) at the A.M. pre-brush, 25.6% lower (p = 0.0014) at the A.M. post-brush, and 19.8% lower (p = 0.0057) at the P.M. measure relative to the AlF3/Chx dentifrice. The blend-a-med EXPERT GUMS PROTECTION toothpaste inhibits plaque regrowth, both overnight and during the day, to a significantly greater degree than Lacalut Aktiv. Additionally, immediately after brushing with blend-a-med EXPERT GUMS PROTECTION, subjects had significantly less plaque than after brushing with Lacalut Aktiv.

Prevalence of subclinical atherosclerosis is increased in systemic sclerosis and is associated with serum proteins: a cross-sectional, controlled study of carotid ultrasound.

PubMed

Schiopu, Elena; Au, Karen M; McMahon, Maureen A; Kaplan, Mariana J; Divekar, Anagha; Singh, Ram R; Furst, Daniel E; Clements, Philip J; Ragvendra, Nagesh; Zhao, Wenpu; Maranian, Paul; Khanna, Dinesh

2014-04-01

SSc is associated with an increased prevalence of atherosclerosis (ATS). This study assessed the prevalence of subclinical ATS as measured by carotid US and explored serum proteins to identify potential biomarkers of SSc-ATS. Forty-six SSc female patients and 46 age- and ethnicity-matched controls underwent carotid US to assess the presence of plaque and carotid intima media thickness (CIMT). Abstracted data included demographics, ATS risk factors and serum measurements [cholesterol, proinflammatory high-density lipoprotein (piHDL), CRP, lipoproteins]. Serum cytokines/proteins analyses included circulating type I IFN activity by quantifying IFN-inducible genes, soluble junctional adhesion molecule A (sJAM-A) and 100 serum proteins by using a microplate-based multiplex platform. Proteins significant at P < 0.05 on bivariate analyses for the presence of plaque were used to develop a composite measure. Patients with SSc had more plaque (45.6% vs 19.5%, P = 0.01) but similar CIMT compared with controls. Multiplex analysis detected significant associations between serum proteins of inflammation, vasculopathy and fibrosis with ATS in SSc, including IL-2, IL-6, CRP, keratinocyte growth factor, intercellular adhesion molecule 1, endoglin, plasminogen activator inhibitor 1 and insulin-like growth factor binding protein 3 associated with carotid plaque. Myeloid progenitor inhibitory factor 1, serum amyloid A, thrombomodulin, N-terminal pro-brain natriuretic peptide (BNP), and Clara cell secretory protein 16 kD correlated with CIMT. The median composite score for the plaque group was 6 and for the no plaque group it was 2 (P < 0.0001). Patients with SSc have a higher prevalence of carotid plaque than matched controls, and patients with SSc-plaque vs patients without plaque have elevated serum proteins implicated in both vasculopathy and fibrosis. Further studies are needed to evaluate the role of these proteins in SSc compared with healthy controls.

Remineralisation by chewing sugar-free gums in a randomised, controlled in situ trial including dietary intake and gauze to promote plaque formation.

PubMed

Cochrane, N J; Shen, P; Byrne, S J; Walker, G D; Adams, G G; Yuan, Y; Reynolds, C; Hoffmann, B; Dashper, S G; Reynolds, E C

2012-01-01

Remineralisation has been shown to be an effective mechanism of preventing the progression of enamel caries. The aim of this double-blind, randomised, cross-over in situ study was to compare enamel remineralisation by chewing sugar-free gum with or without casein phosphopeptide amorphous calcium phosphate (CPP-ACP) where the enamel lesions were exposed to dietary intake and some were covered with gauze to promote plaque formation. Participants wore removable palatal appliances containing 3 recessed enamel half-slabs with subsurface lesions covered with gauze and 3 without gauze. Mineral content was measured by transverse microradiography, and plaque composition was analysed by real-time polymerase chain reaction. For both the gauze-free and gauze-covered lesions, the greatest amount of remineralisation was produced by the CPP-ACP sugar-free gum, followed by the gum without CPP-ACP and then the no-gum control. Recessing the enamel in the appliance allowed plaque accumulation without the need for gauze. There was a trend of less remineralisation and greater variation in mineral content for the gauze-covered lesions. The cell numbers of total bacteria and streptococci were slightly higher in the plaque from the gauze-covered enamel for 2 of the 3 treatment legs; however, there was no significant difference in Streptococcus mutans cell numbers. In conclusion, chewing sugar-free gum containing CPP-ACP promoted greater levels of remineralisation than a sugar-free gum without CPP-ACP or a no-gum control using an in situ remineralisation model including dietary intake irrespective of whether gauze was used to promote plaque formation or not. Copyright © 2012 S. Karger AG, Basel.

Histological Stratification of Thick and Thin Plaque Psoriasis Explores Molecular Phenotypes with Clinical Implications

PubMed Central

Kim, Dong Joo; Brodmerkel, Carrie; Correa da Rosa, Joel; Krueger, James G.; Suárez-Fariñas, Mayte

2015-01-01

Psoriasis, which presents as red, scaly patches on the body, is a common, autoimmune skin disease that affects 2 to 3 percent of the world population. To leverage recent molecular findings into the personalized treatment of psoriasis, we need a strategy that integrates clinical stratification with molecular phenotyping. In this study, we sought to stratify psoriasis patients by histological measurements of epidermal thickness, and to compare their molecular characterizations by gene expression, serum cytokines, and response to biologics. We obtained histological measures of epidermal thickness in a cohort of 609 psoriasis patients, and identified a mixture of two subpopulations—thick and thin plaque psoriasis—from which they were derived. This stratification was verified in a subcohort of 65 patients from a previously published study with significant differences in inflammatory cell infiltrates in the psoriatic skin. Thick and thin plaque psoriasis shared 84.8% of the meta-analysis-derived psoriasis transcriptome, but a stronger dysregulation of the meta-analysis-derived psoriasis transcriptome was seen in thick plaque psoriasis on microarray. RT-PCR revealed that gene expression in thick and thin plaque psoriasis was different not only within psoriatic lesional skin but also in peripheral non-lesional skin. Additionally, differences in circulating cytokines and their changes in response to biologic treatments were found between the two subgroups. All together, we were able to integrate histological stratification with molecular phenotyping as a way of exploring clinical phenotypes with different expression levels of the psoriasis transcriptome and circulating cytokines. PMID:26176783

OCT-measured plaque free wall angle is indicative for plaque burden: overcoming the main limitation of OCT?

PubMed

Hoogendoorn, Ayla; Gnanadesigan, Muthukaruppan; Zahnd, Guillaume; van Ditzhuijzen, Nienke S; Schuurbiers, Johan C H; van Soest, Gijs; Regar, Evelyn; Wentzel, Jolanda J

2016-10-01

The aim of this study was to investigate the relationship between the plaque free wall (PFW) measured by optical coherence tomography (OCT) and the plaque burden (PB) measured by intravascular ultrasound (IVUS). We hypothesize that measurement of the PFW could help to estimate the PB, thereby overcoming the limited ability of OCT to visualize the external elastic membrane in the presence of plaque. This could enable selection of the optimal stent-landing zone by OCT, which is traditionally defined by IVUS as a region with a PB < 40 %. PB (IVUS) and PFW angle (OCT and IVUS) were measured in 18 matched IVUS and OCT pullbacks acquired in the same coronary artery. We determined the relationship between OCT measured PFW (PFWOCT) and IVUS PB (PBIVUS) by non-linear regression analysis. An ROC-curve analysis was used to determine the optimal cut-off value of PFW angle for the detection of PB < 40 %. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated. There is a significant correlation between PFWOCT and PBIVUS (r(2) = 0.59). The optimal cut-off value of the PFWOCT for the prediction of a PBIVUS < 40 % is ≥220° with a PPV of 78 % and an NPV of 84 %. This study shows that PFWOCT can be considered as a surrogate marker for PBIVUS, which is currently a common criterion to select an optimal stent-landing zone.

Association between Randall's Plaque and Calcifying Nanoparticles

NASA Technical Reports Server (NTRS)

Citfcioglu, Neva; Vejdani, Kaveh; Lee, Olivia; Mathew, Grace; Aho, Katja M.; Kajander, Olavi; McKay, David S.; Jones, Jeffrey A.; Feiveson, Alan H.; Stoller, Marshall L.

2007-01-01

Randall initially described calcified subepithelial papillary plaques, which he hypothesized as nidi for kidney stone formation. The discovery of calcifying nanoparticles (CNP) in many calcifying processes of human tissues has raised another hypothesis about their possible involvement in urinary stone formation. This research is the first attempt to investigate the potential association of these two hypotheses. We collected renal papilla and blood samples from 17 human patients who had undergone laparoscopic nephrectomy due to neoplasia. Immunohistochemical staining (IHS) was applied on the tissue samples using monoclonal antibody 8D10 (mAb) against CNP. Homogenized papillary tissues and serum samples were cultured for CNP. Scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS) analysis were performed on fixed papillary samples. Randall's plaques were visible on gross inspection in 11 out of 17 collected samples. IHS was positive for CNP antigen in 8 of these 11 visually positive samples, but in only 1 of the remaining 6 samples. SEM revealed spherical apatite formations in 14 samples, all of which had calcium and phosphate peaks detected by EDS analysis. From this study, there was some evidence of a link between the presence of Randall's plaques and the detection of CNP, also referred to as nanobacteria. Although causality was not demonstrated, these results suggest that further studies with negative control samples should be made to explore the etiology of Randall's plaque formation, thus leading to a better understanding of the pathogenesis of stone formation.

Variogram methods for texture classification of atherosclerotic plaque ultrasound images

NASA Astrophysics Data System (ADS)

Jeromin, Oliver M.; Pattichis, Marios S.; Pattichis, Constantinos; Kyriacou, Efthyvoulos; Nicolaides, Andrew

2006-03-01

Stroke is the third leading cause of death in the western world and the major cause of disability in adults. The type and stenosis of extracranial carotid artery disease is often responsible for ischemic strokes, transient ischemic attacks (TIAs) or amaurosis fugax (AF). The identification and grading of stenosis can be done using gray scale ultrasound scans. The appearance of B-scan pictures containing various granular structures makes the use of texture analysis techniques suitable for computer assisted tissue characterization purposes. The objective of this study is to investigate the usefulness of variogram analysis in the assessment of ultrasound plague morphology. The variogram estimates the variance of random fields, from arbitrary samples in space. We explore stationary random field models based on the variogram, which can be applied in ultrasound plaque imaging leading to a Computer Aided Diagnosis (CAD) system for the early detection of symptomatic atherosclerotic plaques. Non-parametric tests on the variogram coefficients show that the cofficients coming from symptomatic versus asymptomatic plaques come from distinct distributions. Furthermore, we show significant improvement in class separation, when a log point-transformation is applied to the images, prior to variogram estimation. Model fitting using least squares is explored for anisotropic variograms along specific directions. Comparative classification results, show that variogram coefficients can be used for the early detection of symptomatic cases, and also exhibit the largest class distances between symptomatic and asymptomatic plaque images, as compared to over 60 other texture features, used in the literature.

Tyrosine gated electron transfer is key to the toxic mechanism of Alzheimer's disease beta-amyloid.

PubMed

Barnham, Kevin J; Haeffner, Fredrik; Ciccotosto, Giuseppe D; Curtain, Cyril C; Tew, Deborah; Mavros, Christine; Beyreuther, Konrad; Carrington, Darryl; Masters, Colin L; Cherny, Robert A; Cappai, Roberto; Bush, Ashley I

2004-09-01

Alzheimer's disease (AD) is characterized by the presence of neurofibrillary tangles and amyloid plaques, which are abnormal protein deposits. The major constituent of the plaques is the neurotoxic beta-amyloid peptide (Abeta); the genetics of familial AD support a direct role for this peptide in AD. Abeta neurotoxicity is linked to hydrogen peroxide formation. Abeta coordinates the redox active transition metals, copper and iron, to catalytically generate reactive oxygen species. The chemical mechanism underlying this process is not well defined. With the use of density functional theory calculations to delineate the chemical mechanisms that drive the catalytic production of H2O2 by Abeta/Cu, tyrosine10 (Y10) was identified as a pivotal residue for this reaction to proceed. The relative stability of tyrosyl radicals facilitates the electron transfers that are required to drive the reaction. Confirming the theoretical results, mutation of the tyrosine residue to alanine inhibited H2O2 production, Cu-induced radicalization, dityrosine cross-linking, and neurotoxicity.

Clinical and microbiological effects of mechanical instrumentation and local antimicrobials during periodontal supportive therapy in aggressive periodontitis patients: smoker versus non-smoker patients.

PubMed

Guarnelli, Maria Elena; Farina, Roberto; Cucchi, Alessandro; Trombelli, Leonardo

2010-11-01

To compare the clinical and microbiological effects of ultrasonic mechanical instrumentation (UMI) associated to home-care use of amine fluoride/stannous fluoride (AmF/SnF(2) )-containing mouthrinse and toothpaste in smoker and non-smoker patients affected by generalized aggressive periodontitis (G-AgP) during a recall session of supportive periodontal therapy (SPT). Thirteen smokers and 25 non-smokers G-AgP patients enrolled in an SPT programme received a single session of UMI associated with home-care use of AmF/SnF(2) -containing mouthrinse and toothpaste. Clinical and microbiological parameters were assessed pre-treatment, at 6 and 12 weeks post-treatment. In both groups, UMI plus AmF/SnF(2) -implemented oral hygiene use determined a significant decrease of total bacterial counts, with non-smokers exhibiting a lower count compared with smokers at 12 weeks. No significant differences were observed between smokers and non-smokers in the counts of total pathogens and red complex species at each observation interval. Clinically, a significant reduction of supragingival plaque, gingival inflammation and probing pocket depth was similarly observed in both groups. A combined mechanical/chemical plaque control approach based on UMI and the use of AmF/SnF(2) agents resulted in the reduction of supragingival plaque deposits, gingival inflammation and subgingival periodontal pathogens in G-AgP patients during SPT, with no substantial difference between smokers and non-smokers. © 2010 John Wiley & Sons A/S.

Improved plaque materials for aerospace nickel-cadmium cells

NASA Technical Reports Server (NTRS)

Luksha, E.; Gordy, D. J.

1971-01-01

Improved cadmium electrode substrates with precisely controlled microstructures for possible use in aerospace nickel-cadmium cells were prepared. The preparative technique was a powder metallurgical process in which a fugitive pore-former and a nickel powder were blended, then isostatically compacted, and subsequently sintered. Cadmium electrodes prepared from such substrates were cycle tested using an accelerated tortuous test regime. It was discovered that plaques of 60% or 80% porosity prepared with a 25 micron pore-former were better than state-of-the-art electrodes in terms of efficienty and/or mechanical strength. The 60% structures were particularly outstanding in this respect in that they had efficiencies only 5-10 percentage points lower than state-of-the-art electrodes and vastly superior mechanical properties. This added strength was observed to eliminate cracking and physical degradation of the electrodes during processing and cycling. The cadmium electrodes prepared from the 80% porous substrates proved to be the best electrodes made during the course of the work from the point of view of highest efficiency. Three-point bend tests were used to measure mechanical properties of the plaques produced and also as a general characterization tool. In addition, the BET surface areas of selected specimens was determined. The SEM was used for judging microscopic uniformity and quantitatively determining the induced pore size and various other fine structures in the substrates. The technique of X-ray radiography was used to follow the bulk uniformity of the substrates at various stages of their processing.

Association of traditional cardiovascular risk factors with coronary plaque sub-types assessed by 64-slice computed tomography angiography in a large cohort of asymptomatic subjects.

PubMed

Rivera, Juan J; Nasir, Khurram; Cox, Pedro R; Choi, Eue-Keun; Yoon, Yeonyee; Cho, Iksung; Chun, Eun-Ju; Choi, Sang-Il; Blumenthal, Roger S; Chang, Hyuk-Jae

2009-10-01

Although prior studies have shown that traditional cardiovascular (CV) risk factors are associated with the burden of coronary atherosclerosis, less is known about the relationship of risk factors with coronary plaque sub-types. Coronary computed tomography angiography (CCTA) allows an assessment of both, total disease burden and plaque characteristics. In this study, we investigate the relationship between traditional CV risk factors and the presence and extent of coronary plaque sub-types in a large group of asymptomatic individuals. The study population consisted of 1015 asymptomatic Korean subjects (53+/-10 years; 64% were males) free of known CV disease who underwent 64-slice CCTA as part of a health screening evaluation. We analyzed plaque characteristics on a per-segment basis according to the modified American Heart Association classification. Plaques in which calcified tissue occupied more than 50% of the plaque area were classified as calcified (CAP), <50% calcified area as mixed (MCAP), and plaques without any calcium as non-calcified (NCAP). A total of 215 (21%) subjects had coronary plaque while 800 (79%) had no identifiable disease. Multivariate regression analysis demonstrated that increased age (per decade) and gender are the strongest predictors for the presence of any coronary plaque or the presence of at least one segment of CAP and MCAP (any plaque-age: OR 2.89; 95% CI 2.34, 3.56; male gender: OR 5.21; 95% CI 3.20, 8.49; CAP-age: OR 2.75; 95% CI 2.12, 3.58; male gender: 4.78; 95% CI 2.48, 9.23; MCAP-age: OR 2.62; 95% CI 2.02, 3.39; male gender: OR 4.15; 95% CI 2.17, 7.94). The strongest predictors for the presence of any NCAP were gender (OR 3.56; 95% CI 1.96-6.55) and diabetes mellitus (OR 2.87; 95% CI 1.63-5.08). When looking at the multivariate association between the presence of >/=2 coronary segments with a plaque sub-type and CV risk factors, male gender was the strongest predictor for CAP (OR 7.31; 95% CI 2.12, 25.20) and MCAP (OR 5.54; 95% CI 1.84, 16.68). Alternatively, smoking was the strongest predictor for the presence of >/=2 coronary segments with NCAP (OR 4.86; 95% CI 1.68, 14.07). Low-density lipoprotein cholesterol (LDL-C) was only a predictor for the presence and extent of mixed coronary plaque. Age and gender are overall the strongest predictors of atherosclerosis as assessed by CCTA in this large asymptomatic Korean population and these two risk factors are not particularly associated with a specific coronary plaque sub-type. Smoking is a strong predictor of NCAP, which has been suggested by previous reports as a more vulnerable lesion. Whether a specific plaque sub-type is associated with a worse prognosis is yet to be determined by future prospective studies.

Clinical and angiographic characteristics of patients likely to have vulnerable plaques: analysis from the PROSPECT study.

PubMed

Bourantas, Christos V; Garcia-Garcia, Hector M; Farooq, Vasim; Maehara, Akiko; Xu, Ke; Généreux, Philippe; Diletti, Roberto; Muramatsu, Takashi; Fahy, Martin; Weisz, Giora; Stone, Gregg W; Serruys, Patrick W

2013-12-01

This study sought to determine the clinical and angiographic variables that would identify patients with high-risk "vulnerable" coronary plaques. In the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study, in patients successfully treated for acute coronary syndrome (ACS), plaque composition, plaque burden, and minimal luminal area as detected by 3-vessel radiofrequency intravascular ultrasound (IVUS) imaging were associated with an increased risk of developing future events from untreated atherosclerotic lesions (vulnerable plaques). Whether baseline demographic and angiographic findings can be used to identify patients most likely to have vulnerable coronary plaques has not been examined. On the basis of 3-vessel radiofrequency IVUS imaging, patents in the PROSPECT trial were classified in 2 groups according to whether or not one or more untreated high-risk plaques were present, defined as having ≥2 high-risk features (a thin-cap fibroatheroma, plaque burden ≥70%, and/or minimal luminal area ≤4 mm(2)). The high-risk group (those with one or more high-risk lesions) had higher Framingham risk score (7.5 ± 3.4 vs. 6.9 ± 3.3; p = 0.04), more extensive coronary artery disease, and more nonculprit lesion-related cardiovascular events during the 3-year follow-up (hazard ratio: 2.63; 95% confidence interval: 1.62 to 3.66; p < 0.0001). However, demographic factors had poor discrimination in detecting high-risk patients (area under the curve 0.55), and discrimination was only slightly improved when angiographic variables were entered into the model (area under the curve 0.64). Clinical and angiographic characteristics had poor predictive accuracy in identifying patients with untreated high-risk plaques related to future adverse events. This finding highlights the potential value of comprehensive 3-vessel imaging assessment (either invasive or noninvasive) to evaluate plaque phenotype for more accurate risk stratification of patients admitted with ACS. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Differentiation of early from advanced coronary atherosclerotic lesions: systematic comparison of CT, intravascular US, and optical frequency domain imaging with histopathologic examination in ex vivo human hearts.

PubMed

Maurovich-Horvat, Pál; Schlett, Christopher L; Alkadhi, Hatem; Nakano, Masataka; Stolzmann, Paul; Vorpahl, Marc; Scheffel, Hans; Tanaka, Atsushi; Warger, William C; Maehara, Akiko; Ma, Shixin; Kriegel, Matthias F; Kaple, Ryan K; Seifarth, Harald; Bamberg, Fabian; Mintz, Gary S; Tearney, Guillermo J; Virmani, Renu; Hoffmann, Udo

2012-11-01

To establish an ex vivo experimental setup for imaging coronary atherosclerosis with coronary computed tomographic (CT) angiography, intravascular ultrasonography (US), and optical frequency domain imaging (OFDI) and to investigate their ability to help differentiate early from advanced coronary plaques. All procedures were performed in accordance with local and federal regulations and the Declaration of Helsinki. Approval of the local Ethics Committee was obtained. Overall, 379 histologic cuts from nine coronary arteries from three donor hearts were acquired, coregistered among modalities, and assessed for the presence and composition of atherosclerotic plaque. To assess the discriminatory capacity of the different modalities in the detection of advanced lesions, c statistic analysis was used. Interobserver agreement was assessed with the Cohen κ statistic. Cross sections without plaque at coronary CT angiography and with fibrous plaque at OFDI almost never showed advanced lesions at histopathologic examination (odds ratio [OR]: 0.02 and 0.06, respectively; both P<.0001), while mixed plaque at coronary CT angiography, calcified plaque at intravascular US, and lipid-rich plaque at OFDI were associated with advanced lesions (OR: 2.49, P=.0003; OR: 2.60, P=.002; and OR: 31.2, P<.0001, respectively). OFDI had higher accuracy for discriminating early from advanced lesions than intravascular US and coronary CT angiography (area under the receiver operating characteristic curve: 0.858 [95% confidence interval {CI}: 0.802, 0.913], 0.631 [95% CI: 0.554, 0.709], and 0.679 [95% CI: 0.618, 0.740]; respectively, P<.0001). Interobserver agreement was excellent for OFDI and coronary CT angiography (κ=0.87 and 0.85, respectively) and was good for intravascular US (κ=0.66). Systematic and standardized comparison between invasive and noninvasive modalities for coronary plaque characterization in ex vivo specimens demonstrated that coronary CT angiography and intravascular US are reasonably associated with plaque composition and lesion grading according to histopathologic findings, while OFDI was strongly associated. These data may help to develop initial concepts of sequential imaging strategies to identify patients with advanced coronary plaques. © RSNA, 2012

Effects of Hyperthyroidism on Coronary Artery Disease: A Computed Tomography Angiography Study.

PubMed

Beyer, Christoph; Plank, Fabian; Friedrich, Guy; Wildauer, Matthias; Feuchtner, Gudrun

2017-10-01

Changes in thyroid hormone concentration can negatively affect the cardiovascular system. Subclinical hyperthyroidism has been linked to an increase of cardiovascular heart disease, however, clinical effects and significance are still uncertain. Therefore, we analyzed coronary computed tomography angiographies of patients with overt and subclinical hyperthyroidism for quantitative parameters and plaque morphology. Seven hundred forty-four (47.1% female) patients who underwent coronary computed tomography angiography were stratified into 3 groups: 51 patients with overt, 74 patients with subclinical hyperthyroidism, and 619 patients with euthyroidism. Analysis included grades of stenosis (no stenosis = 0, mild < 50%, intermediate 50%-70%, or high-grade > 70%) and plaque types (noncalcified, mixed, and calcified), segment involvement score (SIS), noncalcified SIS, and high-risk plaque features (napkin ring sign, low attenuation plaque, spotty calcifications, positive remodelling). Patients with overt and subclinical hyperthyroidism had more high-grade stenoses (39.2% vs 37.8% vs 24.2%; P = 0.007) and a higher coronary calcium score (456.5 vs 199.5 vs 155.9; P < 0.0001). Also, a total higher plaque burden has been found (SIS: 3.3 vs 3.2 vs 2.2; P < 0.0001; noncalcified SIS (1.2 vs 1.1 vs 0.6; P < 0.0001)). Patients with overt hyperthyroidism, followed by those with subclinical hyperthyroidism, had the most high-risk plaque features: napkin ring (21.6% vs 9.5% vs 6.0%, P < 0.0001), low attenuation plaque (35.3% vs 27% vs 8.7%, P < 0.0001), spotty calcification (35.3% vs 18.9% vs 19.1%, P = 0.02), and positive remodelling (37.3% vs 37.8% vs 25.5%, P = 0.02). After a mean follow-up of 168 months, significantly more revascularizations were documented for hyperthyroid patients. Patients with subclinical and overt hyperthyroidism showed more high-grade coronary stenoses, plaque burden, and high-risk plaque features than patients with euthyroidism, which indicates that an increase of thyroid hormones might lead to coronary vascular degeneration and plaque instability. Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Study of process variables associated with manufacturing hermetically-sealed nickel-cadmium cells

NASA Technical Reports Server (NTRS)

Miller, L.; Doan, D. J.; Carr, E. S.

1971-01-01

A program to determine and study the critical process variables associated with the manufacture of aerospace, hermetically-sealed, nickel-cadmium cells is described. The determination and study of the process variables associated with the positive and negative plaque impregnation/polarization process are emphasized. The experimental data resulting from the implementation of fractional factorial design experiments are analyzed by means of a linear multiple regression analysis technique. This analysis permits the selection of preferred levels for certain process variables to achieve desirable impregnated plaque characteristics.

Low-levels of fluoride in plaque and saliva and their effects on the demineralisation and remineralisation of enamel; role of fluoride toothpastes.

PubMed

Lynch, R J M; Navada, R; Walia, R

2004-01-01

To summarise support for current consensus on the likely means by which fluoride toothpastes reduce caries and review some relevant studies of the effect of low levels of fluoride on the demineralisation and remineralisation of enamel. The major anti-caries effect of fluoride toothpastes is thought to result from small but protracted elevations in levels of fluoride in plaque and saliva. Fluoride incorporated into enamel systemically does not reduce enamel solubility sufficiently to exert an anti-caries effect. Fluoride has the potential to exert an anti-caries benefit largely through three mechanisms; inhibition of demineralisation, promotion of remineralisation and interference with bacterial growth and metabolism. However, the low levels of fluoride thought to influence caries are insufficient to have a significant effect via the latter mechanism. Thus reductions in caries resulting from the use of fluoride toothpastes can be linked to modification of the demineralisation/remineralisation balance by direct effects on dental mineral exerted topically by low levels of fluoride. Numerous in vitro studies have shown that low levels of fluoride, typical of those found after many hours in resting plaque and saliva, and resulting from the regular use of fluoride toothpastes, can have a profound effect on enamel demineralisation and remineralisation.

Deep brain two-photon NIR fluorescence imaging for study of Alzheimer's disease

NASA Astrophysics Data System (ADS)

Chen, Congping; Liang, Zhuoyi; Zhou, Biao; Ip, Nancy Y.; Qu, Jianan Y.

2018-02-01

Amyloid depositions in the brain represent the characteristic hallmarks of Alzheimer's disease (AD) pathology. The abnormal accumulation of extracellular amyloid-beta (Aβ) and resulting toxic amyloid plaques are considered to be responsible for the clinical deficits including cognitive decline and memory loss. In vivo two-photon fluorescence imaging of amyloid plaques in live AD mouse model through a chronic imaging window (thinned skull or craniotomy) provides a mean to greatly facilitate the study of the pathological mechanism of AD owing to its high spatial resolution and long-term continuous monitoring. However, the imaging depth for amyloid plaques is largely limited to upper cortical layers due to the short-wavelength fluorescence emission of commonly used amyloid probes. In this work, we reported that CRANAD-3, a near-infrared (NIR) probe for amyloid species with excitation wavelength at 900 nm and emission wavelength around 650 nm, has great advantages over conventionally used probes and is well suited for twophoton deep imaging of amyloid plaques in AD mouse brain. Compared with a commonly used MeO-X04 probe, the imaging depth of CRANAD-3 is largely extended for open skull cranial window. Furthermore, by using two-photon excited fluorescence spectroscopic imaging, we characterized the intrinsic fluorescence of the "aging pigment" lipofuscin in vivo, which has distinct spectra from CRANAD-3 labeled plaques. This study reveals the unique potential of NIR probes for in vivo, high-resolution and deep imaging of brain amyloid in Alzheimer's disease.

Molecular magnetic resonance imaging of atherosclerotic vessel wall disease.

PubMed

Nörenberg, Dominik; Ebersberger, Hans U; Diederichs, Gerd; Hamm, Bernd; Botnar, René M; Makowski, Marcus R

2016-03-01

Molecular imaging aims to improve the identification and characterization of pathological processes in vivo by visualizing the underlying biological mechanisms. Molecular imaging techniques are increasingly used to assess vascular inflammation, remodeling, cell migration, angioneogenesis and apoptosis. In cardiovascular diseases, molecular magnetic resonance imaging (MRI) offers new insights into the in vivo biology of pathological vessel wall processes of the coronary and carotid arteries and the aorta. This includes detection of early vascular changes preceding plaque development, visualization of unstable plaques and assessment of response to therapy. The current review focuses on recent developments in the field of molecular MRI to characterise different stages of atherosclerotic vessel wall disease. A variety of molecular MR-probes have been developed to improve the non-invasive detection and characterization of atherosclerotic plaques. Specifically targeted molecular probes allow for the visualization of key biological steps in the cascade leading to the development of arterial vessel wall lesions. Early detection of processes which lead to the development of atherosclerosis and the identification of vulnerable atherosclerotic plaques may enable the early assessment of response to therapy, improve therapy planning, foster the prevention of cardiovascular events and may open the door for the development of patient-specific treatment strategies. Targeted MR-probes allow the characterization of atherosclerosis on a molecular level. Molecular MRI can identify in vivo markers for the differentiation of stable and unstable plaques. Visualization of early molecular changes has the potential to improve patient-individualized risk-assessment.

Antioxidant proteins TSA and PAG interact synergistically with Presenilin to modulate Notch signaling in Drosophila.

PubMed

Wangler, Michael F; Reiter, Lawrence T; Zimm, Georgianna; Trimble-Morgan, Jennifer; Wu, Jane; Bier, Ethan

2011-07-01

Alzheimer's disease (AD) pathogenesis is characterized by senile plaques in the brain and evidence of oxidative damage. Oxidative stress may precede plaque formation in AD; however, the link between oxidative damage and plaque formation remains unknown. Presenilins are transmembrane proteins in which mutations lead to accelerated plaque formation and early-onset familial Alzheimer's disease. Presenilins physically interact with two antioxidant enzymes thiol-specific antioxidant (TSA) and proliferation-associated gene (PAG) of the peroxiredoxin family. The functional consequences of these interactions are unclear. In the current study we expressed a presenilin transgene in Drosophila wing and sensory organ precursors of the fly. This caused phenotypes typical of Notch signaling loss-of-function mutations. We found that while expression of TSA or PAG alone produced no phenotype, co-expression of TSA and PAG with presenilin led to an enhanced Notch loss-of-function phenotype. This phenotype was more severe and more penetrant than that caused by the expression of Psn alone. In order to determine whether these phenotypes were indeed affecting Notch signaling, this experiment was performed in a genetic background carrying an activated Notch (Abruptex) allele. The phenotypes were almost completely rescued by this activated Notch allele. These results link peroxiredoxins with the in vivo function of Presenilin, which ultimately connects two key pathogenetic mechanisms in AD, namely, antioxidant activity and plaque formation, and raises the possibility of a role for peroxiredoxin family members in Alzheimer's pathogenesis.

A 12-week clinical comparison of an oscillating-rotating power brush versus a marketed sonic brush with self-adjusting technology in reducing plaque and gingivitis.

PubMed

Klukowska, Malgorzata; Grender, Julie M; Conde, Erinn; Goyal, C Ram

2013-01-01

The aim of this investigation was to assess the comparative gingivitis and plaque reduction efficacy of a leading oscillating-rotating power toothbrush and a recently introduced sonic toothbrush in adults with gingivitis. This was a 12-week, randomized and controlled, parallel group, examiner-blind, single-center clinical study of 130 adults with pre-existing gingivitis and plaque. At baseline, the Modified Gingival Index (MGI), Gingival Bleeding Index (GBI), and total number of bleeding sites were assessed, along with plaque levels (whole mouth, gingival margin, and interproximal) via the Rustogi Modified Navy Plaque Index (RMNPI). Qualified subjects were randomly assigned to one of two power toothbrush test groups: the Oral-B Triumph with SmartGuide (marketed in the United States as the Oral-B Professional Care SmartSeries 5000 [D34]) oscillating-rotating brush, or the Colgate ProClinical A1500 (also marketed as elmex ProClinical) sonic brush. Subjects brushed at home for two minutes twice daily with their assigned power toothbrush and a marketed sodium fluoride dentifrice, and were reevaluated for gingivitis at Week 4 and Week 12 via the MGI, GBI, and total number of bleeding sites, and for plaque reduction via the RMNPI. Ninety-seven percent (97%) of the 130 enrolled subjects completed the trial and 62 and 65 subjects in the oscillating-rotating and sonic brush groups, respectively, had evaluable data for analysis. Statistically significant mean reductions in all three gingivitis parameters and plaque relative to baseline were seen at both Weeks 4 and 12 with unsupervised use of both test toothbrushes (p < 0.001). The oscillating-rotating power brush provided statistically significantly superior reductions compared to the sonic brush in mean adjusted MGI (31% and 29% at Weeks 4 and 12, respectively; p < 0.001), GBI (17% at Week 12; p = 0.047), and total number of bleeding sites (48% and 30% at Weeks 4 and 12, respectively; p = 0.002), and produced statistically significantly greater relative mean adjusted plaque reductions for RMNPI whole mouth plaque (38% and 24% at Weeks 4 and 12, respectively; p < 0.001), gingival margin plaque (36% at Week 4; p = 0.004), and interproximal plaque (39% and 26% at Weeks 4 and 12, respectively; p < 0.001). Both power toothbrushes were well-tolerated. An advanced oscillating-rotating power toothbrush produced substantial, statistically superior reductions in plaque and gingivitis via multiple outcome measures compared to a new sonic toothbrush after both four weeks and 12 weeks of tooth brushing.

Using a portable sulfide monitor as a motivational tool: a clinical study.

PubMed

Uppal, Ranjit Singh; Malhotra, Ranjan; Grover, Vishakha; Grover, Deepak

2012-01-01

Bad breath has a significant impact on daily life of those who suffer from it. Oral malodor may rank only behind dental caries and periodontal disease as the cause of patient's visit to dentist. An aim of this study was to use a portable sulfide monitor as a motivational tool for encouraging the patients towards the better oral hygiene by correlating the plaque scores with sulfide monitor scores, and comparing the sulfide monitor scores before and after complete prophylaxis and 3 months after patient motivation. 30 patients with chronic periodontitis, having chief complaint of oral malodor participated in this study. At first visit, the plaque scores (P1) and sulfide monitor scores before (BCR1) and after complete oral prophylaxis (BCR2) were taken. Then the patients were motivated towards the better oral hygiene. After 3 months, plaque scores (P2) and sulfide monitor scores (BCR3) were recorded again. It was done using SPSS (student package software for statistical analysis). Paired sample test was performed. Statistically significant reduction in sulfide monitor scores was reported after the complete oral prophylaxis and 3 months after patient motivation. Plaque scores were significantly reduced after a period of 3 months. Plaque scores and breathchecker scores were positively correlated. An intensity of the oral malodor was positively correlated with the plaque scores. The portable sulfide monitor was efficacious in motivating the patients towards the better oral hygiene.

Use of non-linear mixed-effects modelling and regression analysis to predict the number of somatic coliphages by plaque enumeration after 3 hours of incubation.

PubMed

Mendez, Javier; Monleon-Getino, Antonio; Jofre, Juan; Lucena, Francisco

2017-10-01

The present study aimed to establish the kinetics of the appearance of coliphage plaques using the double agar layer titration technique to evaluate the feasibility of using traditional coliphage plaque forming unit (PFU) enumeration as a rapid quantification method. Repeated measurements of the appearance of plaques of coliphages titrated according to ISO 10705-2 at different times were analysed using non-linear mixed-effects regression to determine the most suitable model of their appearance kinetics. Although this model is adequate, to simplify its applicability two linear models were developed to predict the numbers of coliphages reliably, using the PFU counts as determined by the ISO after only 3 hours of incubation. One linear model, when the number of plaques detected was between 4 and 26 PFU after 3 hours, had a linear fit of: (1.48 × Counts 3 h + 1.97); and the other, values >26 PFU, had a fit of (1.18 × Counts 3 h + 2.95). If the number of plaques detected was <4 PFU after 3 hours, we recommend incubation for (18 ± 3) hours. The study indicates that the traditional coliphage plating technique has a reasonable potential to provide results in a single working day without the need to invest in additional laboratory equipment.

Use of a disclosed plaque visualization technique improved the self-performed, tooth brushing ability of primary schoolchildren.

PubMed

Chounchaisithi, Napa; Santiwong, Busayarat; Sutthavong, Sirikarn; Asvanit, Pompun

2014-02-01

Disclosing agents have a long history of use as an aid in children's tooth brushing instruction. However, their benefit when used to improve self-performed tooth brushing ability without any tooth brushing instruction has not been investigated. To evaluate the effect of disclosed plaque visualization on improving the self-performed, tooth brushing ability of primary school children. A cluster-randomized, crossover study was conducted in Nakhon Nayok province, Thailand. A total of 122 second-grade schoolchildren, aged 8-10 years old, from 12 schools were randomly divided into 2 groups. The first group was assigned to brush with disclosed plaque visualization, while the other group brushed without disclosed plaque visualization. One month later the groups switched procedures. Tooth brushing ability was evaluated by the subjects' reduction in patient hygiene performance (PHP) scores. The data were analyzed using repeated-measures analysis of variance, with significance set at p<0.05. Disclosed plaque visualization had a significant effect on improving the children's self-performed, tooth brushing ability in all areas of the mouth (p<0.001), particularly for anterior teeth, mandibular teeth, buccal surfaces, and areas adjacent to the gingival margin (p<0.001). Disclosed plaque visualization is a viable technique to improve children's self-performed tooth brushing ability, and could be used in school-based oral health promotion programs.

Traditional Chinese medication Tongxinluo attenuates apoptosis in ox-LDL-stimulated macrophages by enhancing Beclin-1-induced autophagy.

PubMed

Chen, Yifei; Li, Mengmeng; Zhang, Yu; Di, Mingxue; Chen, Weijia; Liu, Xiaolin; Yu, Fangpu; Wang, Han; Zhen, Xi; Zhang, Mei

2018-06-22

In advanced atherosclerosis, a large number of necrotic core increases plaque vulnerability, which leads to the occurrence of acute atherothrombotic cardiovascular events. Macrophage apoptosis plays an important role in secondary necrosis. The present study aimed to examine and describe the effect of the traditional Chinese medication Tongxinluo (TXL) on macrophage apoptosis in advanced atherosclerotic plaques and to explore its mechanism. By observing the effect of TXL on ox-LDL-stimulated macrophage apoptosis, it was shown that TXL significantly inhibited ox-LDL-induced apoptosis of macrophages by enhancing autophagy. Therapeutic mechanism of TXL included increasing the expression of Beclin-1 and improving the dissociation of Bcl-2-Beclin-1 Complex. Apolipoprotein E knockout (apoE-/-) mice with a high fat diet were divided into four groups: saline group (Saline gavage), low dose TXL group (0.38 g/kg/d, gavage), medium dose TXL group (0.75 g/kg/day, gavage), and high dose TXL group (1.5 g/kg/day, gavage). 4 weeks after carotid-artery surgery, lentiviral of Beclin-1 silencing was injected through the tail vein. TXL treatment significantly reduced macrophage apoptosis dose-dependently and the result was blocked by Beclin-1 silencing. In addition, the increased Lc3b dots by TXL almost localized to macrophages in advanced atherosclerotic plaque. Compared with the same dose of TXL shBeclin-1 group, plaque area and vulnerability index of TXL groups decreased. The anti-apoptosis effects of TXL on atherosclerosis was related to the improvement of autophagy via Beclin-1. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Piperlongumine inhibits atherosclerotic plaque formation and vascular smooth muscle cell proliferation by suppressing PDGF receptor signaling

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

Son, Dong Ju; Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA; Kim, Soo Yeon

2012-10-19

Highlights: Black-Right-Pointing-Pointer Anti-atherogenic effect of PL was examined using partial carotid ligation model in ApoE KO mice. Black-Right-Pointing-Pointer PL prevented atherosclerotic plaque development, VSMCs proliferation, and NF-{kappa}B activation. Black-Right-Pointing-Pointer Piperlongumine reduced vascular smooth muscle cell activation through PDGF-R{beta} and NF-{kappa}B-signaling. Black-Right-Pointing-Pointer PL may serve as a new therapeutic molecule for atherosclerosis treatment. -- Abstract: Piperlongumine (piplartine, PL) is an alkaloid found in the long pepper (Piper longum L.) and has well-documented anti-platelet aggregation, anti-inflammatory, and anti-cancer properties; however, the role of PL in prevention of atherosclerosis is unknown. We evaluated the anti-atherosclerotic potential of PL in an in vivo murinemore » model of accelerated atherosclerosis and defined its mechanism of action in aortic vascular smooth muscle cells (VSMCs) in vitro. Local treatment with PL significantly reduced atherosclerotic plaque formation as well as proliferation and nuclear factor-kappa B (NF-{kappa}B) activation in an in vivo setting. PL treatment in VSMCs in vitro showed inhibition of migration and platelet-derived growth factor BB (PDGF-BB)-induced proliferation to the in vivo findings. We further identified that PL inhibited PDGF-BB-induced PDGF receptor beta activation and suppressed downstream signaling molecules such as phospholipase C{gamma}1, extracellular signal-regulated kinases 1 and 2 and Akt. Lastly, PL significantly attenuated activation of NF-{kappa}B-a downstream transcriptional regulator in PDGF receptor signaling, in response to PDGF-BB stimulation. In conclusion, our findings demonstrate a novel, therapeutic mechanism by which PL suppresses atherosclerosis plaque formation in vivo.« less

A comparative study of plaque mutans streptococci levels in children receiving glass ionomer cement and amalgam restorations.

PubMed

Ertuğrul, Fahinur; Eltem, Rengin; Eronat, Cemal

2003-01-01

The restorative materials amalgam (Standalloy F) and glass ionomer cements (Chelon Silver) were comparatively investigated to determine the number of mutans streptococci Saliva and plaque were collected from patients before and 40 days after the insertion of their restorations. Total bateria and mutans streptococci counts were found to be statistically significantly reduced when compared with the prerestoration counts in the saliva samples (P<0.001). Microbiological analysis of the dental plaque showed that the number of mutans streptococci in the glass ionomer cements was significantly lower than in the amalgam restorations (P<0.001). This study showed that silver glass ionomer cements inhibited the growth of mutans streptococci.

Control of Plaque and Gingivitis by an Herbal Toothpaste - A Randomised Controlled Study.

PubMed

Geidel, Alexander; Krüger, Monika; Schrödl, Wieland; Jentsch, Holger

To compare the efficacy of an herbal toothpaste with two other chemically active toothpastes regarding plaque and gingivitis control. Seventy-six (27 females and 49 males, mean age 47.8 years, range 40-58 years) of 84 initial participants with slight and moderate chronic periodontitis used standardised manual toothbrushes and their usual technique for daily manual mechanical plaque control for 24 weeks of supportive periodontal therapy. The volunteers were randomly assigned to one of 3 groups: group 1 used the herbal toothpaste, group 2 a triclosan/copolymer toothpaste, and group 3 an amine/stannous fluoride toothpaste. OHI, API, SBI, BOP, PD and AL were recorded at baseline and after 6, 12 and 24 weeks (PD and AL only at baseline). The Kruskal-Wallis, Mann-Whitney U-, Friedman, and Wilcoxon tests were used for statistical analysis. Moderate changes occurred in API and OHI in all groups. The herbal toothpaste resulted in significantly lower API and OHI in comparison to the fluoride toothpaste during the study period (p = 0.001 and 0.049, minimum and maximum of cases, respectively). SBI was significantly improved in all groups starting after 12 weeks (p = 0.001 and 0.033). BOP remained largely unchanged in all groups and was always significant lower in the herbal toothpaste group (p = 0.001 and 0.036). During the study period of 24 weeks, the herbal toothpaste was as good as the control toothpastes. No side effects were seen. In terms of improving periodontal conditions, the tested herbal toothpaste could be a suitable alternative to conventional toothpastes with artificial chemical ingredients.

Risk factor profile for sudden cardiac death during mountain hiking.

PubMed

Burtscher, M; Pachinger, O; Schocke, M F H; Ulmer, H

2007-07-01

Mountain hiking is associated with a death rate of about 4 deaths per 100,000 hikers annually. About 50 % of all fatalities during mountain hiking are sudden cardiac deaths (SCDs). But there are only few data available regarding risk factors and triggers associated with SCD during mountain hiking. Thus, a case-control analysis between persons who died suddenly during mountain hiking and randomly selected controls was carried out. Risk factor profiles of 179 males over the age of 34 who suffered SCD during mountain hiking were compared to those of 537 matched controls. Hikers who died suddenly during mountain hiking were much more likely to have had a prior MI (17% vs. 0.9%; p < 0.001), known coronary artery disease (CAD) without prior MI (17 % vs. 4%; p < 0.001), diabetes (6% vs. 1 %; p < 0.001), hypercholesterolemia (54 % vs. 20%; p < 0.001), and were less engaged in regular mountain sports activities (31% vs. 58%; p < 0.001) compared to hikers from the control group. Based on the reported relationship between traditional risk factors and coronary plaque morphology, acute plaque rupture with thrombus formation and subsequent lethal arrhythmias may be assumed to be a dominant mechanism precipitating SCD during hiking. In contrast, in skiers especially non-occlusive plaques may precipitate ischemia leading to an imbalance between oxygen demand and supply and subsequent lethal arrhythmias. As preventive measures recommended to hikers at risk, adaptation to regular mountain sports activities by an adequate training program and pharmacological interventions, e.g. lipid lowering drugs, aspirin, and beta-blockers, should be considered.

Aloe vera: It's effect on gingivitis

PubMed Central

Ajmera, Neha; Chatterjee, Anirban; Goyal, Vikas

2013-01-01

Objective: Aloe vera is the oldest medicinal plant that has maintained its popularity over the course of time. It is widely known for its medicinal uses in wound healing, as an analgesic, and for its anti-inflammatory properties. Aim: The aim of this study is to evaluate the anti-inflammatory property of aloe vera mouthwash on plaque-induced gingivitis. Materials and Methods: Forty-five patients who were diagnosed with plaque-induced gingivitis were included in the study. They were divided into three groups with fifteen patients in each group. Group 1 was asked to rinse with 10 ml of aloe vera mouthwash twice daily for three months. Group 2 were treated with scaling only. Group 3 patients were asked to rinse with aloe vera mouthwash and scaling was done. The clinical changes were evaluated with Loe and Silness gingival index (1963) and Muhlemann and Son's Sulcus bleeding index (1971) at baseline, after one month and three months, respectively. Results: The data obtained was compared statistically. The paired ‘t’ test was done for intragroup comparison and one-way analysis of variance with a post hoc Tukey test was used for intergroup comparison. The data was obtained at the baseline, end of first month, and end of the third month. The result suggested reduction in gingival inflammation in all the three groups, but it was more in the aloe vera mouthwash and scaling group. Hence, it was concluded that aloe vera had a significant anti-inflammatory property. Thus, it can be used as an adjunct to mechanical therapy for treating plaque-induced gingivitis. PMID:24174720

Ephrin-A1/EphA4-mediated adhesion of monocytes to endothelial cells.

PubMed

Jellinghaus, Stefanie; Poitz, David M; Ende, Georg; Augstein, Antje; Weinert, Sönke; Stütz, Beryl; Braun-Dullaeus, Rüdiger C; Pasquale, Elena B; Strasser, Ruth H

2013-10-01

The Eph receptors represent the largest family of receptor tyrosine kinases. Both Eph receptors and their ephrin ligands are cell-surface proteins, and they typically mediate cell-to-cell communication by interacting at sites of intercellular contact. The major aim of the present study was to investigate the involvement of EphA4-ephrin-A1 interaction in monocyte adhesion to endothelial cells, as this process is a crucial step during the initiation and progression of the atherosclerotic plaque. Immunohistochemical analysis of human atherosclerotic plaques revealed expression of EphA4 receptor and ephrin-A1 ligand in major cell types within the plaque. Short-time stimulation of endothelial cells with the soluble ligand ephrin-A1 leads to a fourfold increase in adhesion of human monocytes to endothelial cells. In addition, ephrin-A1 further increases monocyte adhesion to already inflamed endothelial cells. EphrinA1 mediates its effect on monocyte adhesion via the activated receptor EphA4. This ephrinA1/EphA4 induced process involves the activation of the Rho signaling pathway and does not require active transcription. Rho activation downstream of EphA4 leads to increased polymerization of actin filaments in endothelial cells. This process was shown to be crucial for the proadhesive effect of ephrin-A1. The results of the present study show that ephrin-A1-induced EphA4 forward signaling promotes monocyte adhesion to endothelial cells via activation of RhoA and subsequent stress-fiber formation by a non-transcriptional mechanism. Copyright © 2013 Elsevier B.V. All rights reserved.

Oral Arginine Metabolism May Decrease the Risk for Dental Caries in Children

PubMed Central

Nascimento, M.M.; Liu, Y.; Kalra, R.; Perry, S.; Adewumi, A.; Xu, X.; Primosch, R.E.; Burne, R.A.

2013-01-01

Arginine metabolism by oral bacteria via the arginine deiminase system (ADS) increases the local pH, which can neutralize the effects of acidification from sugar metabolism and reduce the cariogenicity of oral biofilms. To explore the relationship between oral arginine metabolism and dental caries experience in children, we measured ADS activity in oral samples from 100 children and correlated it with their caries status and type of dentition. Supragingival dental plaque was collected from tooth surfaces that were caries-lesion-free (PF) and from dentinal (PD) and enamel (PE) caries lesions. Regardless of children’s caries status or type of dentition, PF (378.6) had significantly higher ADS activity compared with PD (208.4; p < .001) and PE (194.8; p = .005). There was no significant difference in the salivary arginolytic activity among children with different caries status. Mixed-model analysis showed that plaque caries status is significantly associated with ADS activity despite children’s age, caries status, and dentition (p < .001), with healthy plaque predicting higher ADS activity compared with diseased plaque. Plaque arginine metabolism varies greatly among children and tooth sites, which may affect their susceptibility to caries. PMID:23640952

Comparison of the Effect of Toothbrushing Education Via Video, Lecture and Pamphlet on the Dental Plaque Index of 12-Year-Old Children.

PubMed

Ramezaninia, Javad; Naghibi Sistani, Mohammad Mehdi; Ahangari, Zohreh; Gholinia, Hemmat; Jahanian, Iman; Gharekhani, Samaneh

2018-04-11

The aim of this study was to compare the effect of different modes of toothbrushing education (lecture, video and pamphlet) on the dental plaque index (PI) of adolescents. The cluster randomized intervention was performed on 128 participants aged 12 years, who were allocated into four groups based on the type of intervention. Group 1: no intervention; and groups 2, 3, 4: education via lecture, video, and pamphlet, respectively (n = 32). Their plaque index was measured at the baseline, 24 h and two months later. Data were analyzed by repeated measures analysis of variance (ANOVA), one-way ANOVA, independent and paired t-test. The plaque indices of groups 2, 3, 4 at 24 h (p values < 0.001) and two months (p values < 0.001) showed a significant reduction when compared to the baseline. The lowest PI score was observed in the pamphlet, video and lecture groups at 24 h, respectively. After 2 months, the lowest score of PI was measured in lecture, video and pamphlet groups, respectively; however, these differences were non-significant. Therefore, toothbrushing education via lecture, video and pamphlet reduced the dental plaque index with the same effectiveness.

Effect of posterior crown margin placement on gingival health.

PubMed

Reitemeier, Bernd; Hänsel, Kristina; Walter, Michael H; Kastner, Christian; Toutenburg, Helge

2002-02-01

The clinical impact of posterior crown margin placement on gingival health has not been thoroughly quantified. This study evaluated the effect of posterior crown margin placement with multivariate analysis. Ten general dentists reviewed 240 patients with 480 metal-ceramic crowns in a prospective clinical trial. The alloy was randomly selected from 2 high gold, 1 low gold, and 1 palladium alloy. Variables were the alloy used, oral hygiene index score before treatment, location of crown margins at baseline, and plaque index and sulcus bleeding index scores recorded for restored and control teeth after 1 year. The effect of crown margin placement on sulcular bleeding and plaque accumulation was analyzed with regression models (P<.05). The probability of plaque at 1 year increased with increasing oral hygiene index score before treatment. The lingual surfaces demonstrated the highest probability of plaque. The risk of bleeding at intrasulcular posterior crown margins was approximately twice that at supragingival margins. Poor oral hygiene before treatment and plaque also were associated with sulcular bleeding. Facial sites exhibited a lower probability of sulcular bleeding than lingual surfaces. Type of alloy did not influence sulcular bleeding. In this study, placement of crown margins was one of several parameters that affected gingival health.

Relationship between Pyruvate Kinase Activity and Cariogenic Biofilm Formation in Streptococcus mutans Biotypes in Caries Patients

PubMed Central

Krzyściak, Wirginia; Papież, Monika; Jurczak, Anna; Kościelniak, Dorota; Vyhouskaya, Palina; Zagórska-Świeży, Katarzyna; Skalniak, Anna

2017-01-01

Streptococcus mutans (MS) and its biotype I are the strains most frequently found in dental plaque of young children. Our results indicate that in children pyruvate kinase (PK) activity increases significantly in dental plaque, and this corresponds with caries progression. The MS strains isolated in this study or their main glycolytic metabolism connected with PK enzymes might be useful risk factors for studying the pathogenesis and target points of novel therapies for dental caries. The relationship between PK activity, cariogenic biofilm formation and selected biotypes occurrence was studied. S. mutans dental plaque samples were collected from supragingival plaque of individual deciduous molars in 143 subjects. PK activity was measured at different time points during biofilm formation. Patients were divided into two groups: initial stage decay, and extensive decay. Non-parametric analysis of variance and analysis of covariance were used to determine the connections between S. mutans levels, PK activity and dental caries biotypes. A total of 143 strains were derived from subjects with caries. Biotyping data showed that 62, 23, 50, and 8 strains were classified as biotypes I, II, III, IV, respectively. PK activity in biotypes I, II, and IV was significantly higher in comparison to that in biotype III. The correlation between the level of S. mutans in dental plaque and PK activity was both statistically significant (p < 0.05) and positive. The greater the level of S. mutans in the biofilm (colony count and total biomass), the higher the PK activity; similarly, a low bacterial count correlated with low PK activity. PMID:28559883

Pyrosequencing of Plaque Microflora In Twin Children with Discordant Caries Phenotypes

PubMed Central

Zhang, Meng; Chen, Yongxing; Xie, Lingzhi; Li, Yuhong; Jiang, Han; Du, Minquan

2015-01-01

Despite recent successes in the control of dental caries, the mechanism of caries development remains unclear. To investigate the causes of dental decay, especially in early childhood caries, the supragingival microflora composition of 20 twins with discordant caries phenotypes were analyzed using high-throughput pyrosequencing. In addition, the parents completed a lifestyle questionnaire. A total of 228,789 sequencing reads revealed 10 phyla, 84 genera, and 155 species of microflora, the relative abundances of these strains varied dramatically among the children, Comparative analysis between groups revealed that Veillonella, Corynebacterium and Actinomyces were presumed to be caries-related genera, Fusobacterium, Kingella and Leptotrichia were presumed to be healthy-related genus, yet this six genera were not statistically significant (P>0.05). Moreover, a cluster analysis revealed that the microbial composition of samples in the same group was often dissimilar but that the microbial composition observed in twins was usually similar. Although the genetic and environmental factors that strongly influence the microbial composition of dental caries remains unknown, we speculate that genetic factors primarily influence the individual's susceptibility to dental caries and that environmental factors primarily regulate the microbial composition of the dental plaque and the progression to caries. By using improved twins models and increased sample sizes, our study can be extended to analyze the specific genetic and environmental factors that affect the development of caries. PMID:26524687

Risk factors associated with the carotid intima-media thickness and plaques: ESPREDIA Study.

PubMed

Mostaza, Jose M; Lahoz, Carlos; Salinero-Fort, Miguel A; Laguna, Fernando; Estirado, Eva; García-Iglesias, Francisca; González Alegre, Teresa; Sabín, Concesa; López, Silvia; Cornejo, Victor

To evaluate whether there were any differences in the risk factor profile associated with either the intima-media thickness (IMT) or the presence of carotid plaques. Cross-sectional study in 1475 subjects between 45 and 75years, randomly selected from the population of the Northwest area of Madrid (Spain). They had a physical exam, blood analysis, and ultrasound measurement of the IMT and of the presence of plaques. Mean IMT was 0.725±0.132mm. Forty seven percent of the participants had carotid plaques. In multivariate analysis, factors directly associated with the IMT were, age (β0.227, P<.0001), sex (β0.104, P<.0001), presence of hypertension (β0.082, P=.002), diabetes (β0.130, P<.0001) and current smoking (β0.107, P<.0001), systolic blood pressure (SBP) (β0.219, P<.0001) and LDL-cholesterol levels (β0.074, P=.003), and inversely, diastolic blood pressure (DBP) (β-0.124, P=.001), HDL-cholesterol (β-0.111, P<.0001) and triglyceride levels (β-0.060, P=.028). The presence of plaques was directly associated with age (OR1.08; 95%CI: 1.05-1.10), sex (OR1.95; 95%CI: 1.52-2.51), current smoking (OR2.75; 95%CI: 1.92-3.95), history of hypertension (OR1.58; 95%CI: 1.22-2.04) or diabetes (OR1.84; 95%CI: 1.31-2.58), statin treatment (OR1.56; 95%CI: 1.19-2.04) and SBP (OR1.03; 95%CI: 1.02-1.05), and inversely with DBP (OR0.98; 95%CI: 0.96-0.99). Factors associated with the IMT and the presence of plaques are similar, a finding that support a continuum between muscular layer hypertrophy and arteriosclerosis development. Copyright © 2017 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

Assessing the use of Quantitative Light-induced Fluorescence-Digital as a clinical plaque assessment.

PubMed

Han, Sun-Young; Kim, Bo-Ra; Ko, Hae-Youn; Kwon, Ho-Keun; Kim, Baek-Il

2016-03-01

The aims of this study were to compare the relationship between red fluorescent plaque (RF plaque) area by Quantitative Light-induced Fluorescence-Digital (QLF-D) and disclosed plaque area by two-tone disclosure, and to assess the bacterial composition of the RF plaque by real time-PCR. Fifty healthy subjects were included and 600 facial surfaces of their anterior teeth were examined. QLF-D was taken on two separate occasions (before and after disclosing), and the RF plaque area was calculated based on Plaque Percent Index (PPI). After disclosing, the stained plaque area was analyzed to investigate the relationship with the RF plaque area. The relationship was evaluated using Pearson correlation and paired t-test. Then, the RF and non-red fluorescent (non-RF) plaque samples were obtained from the same subject for real-time PCR test. Total 10 plaque samples were compared the ratio of the 6 of bacteria using Wilcoxon signed rank test. Regarding the paired t-test, the blue-staining plaque area (9.3±9.2) showed significantly similarity with the RF plaque area (9.1±14.9, p=0.80) at ΔR20, however, the red-staining plaque area (31.6±20.9) presented difference from the RF plaque area (p<0.0001). In addition, bacterial composition of Prevotella intermedia and Streptococcus anginosus was associated with substantially more the RF plaque than the non-RF plaque (p<0.05). The plaque assessment method using QLF-D has potential to detect mature plaque, and the plaque area was associated with the blue-staining area using two-tone disclosure. Copyright © 2015 Elsevier B.V. All rights reserved.

Comparison of red autofluorescing plaque and disclosed plaque-a cross-sectional study.

PubMed

Volgenant, Catherine M C; Fernandez Y Mostajo, Mercedes; Rosema, Nanning A M; van der Weijden, Fridus A; Ten Cate, Jacob M; van der Veen, Monique H

2016-12-01

The aim of this cross-sectional study was to assess the correlation between dental plaque scores determined by the measurement of red autofluorescence or by visualization with a two-tone solution. Clinical photographs were used for this study. Overnight plaque from the anterior teeth of 48 participants was assessed for red fluorescence on photographs (taken with a QLF-camera) using a modified Quigley & Hein (mQH) index. A two-tone disclosing solution was applied. Total disclosed plaque was clinically assessed using the mQH index. In addition, total and blue disclosed plaque was scored on clinical photographs using the mQH index. A strong correlation was observed between the total disclosed plaque scored on photographs and the clinical scores (r = 0.70 at site level; r = 0.88 at subject level). The correlation between red fluorescent plaque and total plaque, as assessed on the photographs, was moderate to strong and significant (r = 0.50 at the site level; r = 0.70 at the subject level), with the total plaque scores consistently higher than the red fluorescent plaque scores. The correlation between red fluorescent plaque and blue disclosed plaque was weak to moderate and significant (r = 0.30 at the site level; r = 0.50 at the subject level). Plaque, as scored on white-light photographs, corresponds well with clinically assessed plaque. A weak to moderate correlation between red fluorescing plaque and total disclosed plaque or blue disclosed plaque was found. What at present is considered to be matured dental plaque, which appears blue following the application of a two-tone disclosing solution, is not in agreement with red fluorescent dental plaque assessment.

Prevalence of Subclinical Coronary Artery Disease in Masters Endurance Athletes With a Low Atherosclerotic Risk Profile.

PubMed

Merghani, Ahmed; Maestrini, Viviana; Rosmini, Stefania; Cox, Andrew T; Dhutia, Harshil; Bastiaenan, Rachel; David, Sarojini; Yeo, Tee Joo; Narain, Rajay; Malhotra, Aneil; Papadakis, Michael; Wilson, Mathew G; Tome, Maite; AlFakih, Khaled; Moon, James C; Sharma, Sanjay

2017-07-11

Studies in middle-age and older (masters) athletes with atherosclerotic risk factors for coronary artery disease report higher coronary artery calcium (CAC) scores compared with sedentary individuals. Few studies have assessed the prevalence of coronary artery disease in masters athletes with a low atherosclerotic risk profile. We assessed 152 masters athletes 54.4±8.5 years of age (70% male) and 92 controls of similar age, sex, and low Framingham 10-year coronary artery disease risk scores with an echocardiogram, exercise stress test, computerized tomographic coronary angiogram, and cardiovascular magnetic resonance imaging with late gadolinium enhancement and a 24-hour Holter. Athletes had participated in endurance exercise for an average of 31±12.6 years. The majority (77%) were runners, with a median of 13 marathon runs per athlete. Most athletes (60%) and controls (63%) had a normal CAC score. Male athletes had a higher prevalence of atherosclerotic plaques of any luminal irregularity (44.3% versus 22.2%; P =0.009) compared with sedentary males, and only male athletes showed a CAC ≥300 Agatston units (11.3%) and a luminal stenosis ≥50% (7.5%). Male athletes demonstrated predominantly calcific plaques (72.7%), whereas sedentary males showed predominantly mixed morphology plaques (61.5%). The number of years of training was the only independent variable associated with increased risk of CAC >70th percentile for age or luminal stenosis ≥50% in male athletes (odds ratio, 1.08; 95% confidence interval, 1.01-1.15; P =0.016); 15 (14%) male athletes but none of the controls revealed late gadolinium enhancement on cardiovascular magnetic resonance imaging. Of these athletes, 7 had a pattern consistent with previous myocardial infarction, including 3(42%) with a luminal stenosis ≥50% in the corresponding artery. Most lifelong masters endurance athletes with a low atherosclerotic risk profile have normal CAC scores. Male athletes are more likely to have a CAC score >300 Agatston units or coronary plaques compared with sedentary males with a similar risk profile. The significance of these observations is uncertain, but the predominantly calcific morphology of the plaques in athletes indicates potentially different pathophysiological mechanisms for plaque formation in athletic versus sedentary men. Coronary plaques are more abundant in athletes, whereas their stable nature could mitigate the risk of plaque rupture and acute myocardial infarction. © 2017 American Heart Association, Inc.

Metoprolol Reduces Proinflammatory Cytokines and Atherosclerosis in ApoE−/− Mice

PubMed Central

Ulleryd, Marcus A.; Bernberg, Evelina; Yang, Li Jin; Bergström, Göran M. L.; Johansson, Maria E.

2014-01-01

A few studies in animals and humans suggest that metoprolol (β1-selective adrenoceptor antagonist) may have a direct antiatherosclerotic effect. However, the mechanism behind this protective effect has not been established. The aim of the present study was to evaluate the effect of metoprolol on development of atherosclerosis in ApoE−/− mice and investigate its effect on the release of proinflammatory cytokines. Male ApoE−/− mice were treated with metoprolol (2.5 mg/kg/h) or saline for 11 weeks via osmotic minipumps. Atherosclerosis was assessed in thoracic aorta and aortic root. Total cholesterol levels and Th1/Th2 cytokines were analyzed in serum and macrophage content in lesions by immunohistochemistry. Metoprolol significantly reduced atherosclerotic plaque area in thoracic aorta (P < 0.05 versus Control). Further, metoprolol reduced serum TNFα and the chemokine CXCL1 (P < 0.01 versus Control for both) as well as decreasing the macrophage content in the plaques (P < 0.01 versus Control). Total cholesterol levels were not affected. In this study we found that a moderate dose of metoprolol significantly reduced atherosclerotic plaque area in thoracic aorta of ApoE−/− mice. Metoprolol also decreased serum levels of proinflammatory cytokines TNFα and CXCL1 and macrophage content in the plaques, showing that metoprolol has an anti-inflammatory effect. PMID:25105129

Protease-Activated Receptor-2 Deficiency Attenuates Atherosclerotic Lesion Progression and Instability in Apolipoprotein E-Deficient Mice

PubMed Central

Zuo, Pengfei; Zuo, Zhi; Zheng, Yueyue; Wang, Xin; Zhou, Qianxing; Chen, Long; Ma, Genshan

2017-01-01

Inflammatory mechanisms are involved in the process of atherosclerotic plaque formation and rupture. Accumulating evidence suggests that protease-activated receptor (PAR)-2 contributes to the pathophysiology of chronic inflammation on the vasculature. To directly examine the role of PAR-2 in atherosclerosis, we generated apolipoprotein E/PAR-2 double-deficient mice. Mice were fed with high-fat diet for 12 weeks starting at ages of 6 weeks. PAR-2 deficiency attenuated atherosclerotic lesion progression with reduced total lesion area, reduced percentage of stenosis and reduced total necrotic core area. PAR-2 deficiency increased fibrous cap thickness and collagen content of plaque. Moreover, PAR-2 deficiency decreased smooth muscle cell content, macrophage accumulation, matrix metallopeptidase-9 expression and neovascularization in plaque. Relative quantitative PCR assay using thoracic aorta revealed that PAR-2 deficiency reduced mRNA expression of inflammatory molecules, such as vascular cell adhesion molecule-1, intercellular adhesion molecule-1, tumor necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1. In vitro experiment, we found that PAR-2 deficiency reduced mRNA expression of interferon-γ, interleukin-6, TNF-α and MCP-1 in macrophage under unstimulated and lipopolysaccharide-stimulated conditions. These results suggest that PAR-2 deficiency attenuates the progression and instability of atherosclerotic plaque. PMID:28959204

A Polymethyl Methacrylate-Based Acrylic Dental Resin Surface Bound with a Photoreactive Polymer Inhibits Accumulation of Bacterial Plaque.

PubMed

Fukunishi, Miya; Inoue, Yuuki; Morisaki, Hirobumi; Kuwata, Hirotaka; Ishihara, Kazuhiko; Baba, Kazuyoshi

The aim of this study was to examine the ability of a poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butylmethacrylate-co-2-methacryloyloxyethyloxy-p-azidobenzoate) (PMBPAz) coating on polymethyl methacrylate (PMMA)-based dental resin to inhibit bacterial plaque formation, as well as the polymer's durability against water soaking and chemical exposure. Successful application of PMBPAz on PMMA surfaces was confirmed by x-ray photoelectron spectroscopy (XPS) and measuring the static air contact angle in water. The anti-adhesive effects to bacterial plaque were evaluated using Streptococcus mutans biofilm formation assay. The mechanical and chemical durabilities of the PMBPAz coating on the PMMA surfaces were examined using soaking and immersion tests, respectively. XPS signals for phosphorus and nitrogen atoms and hydrophilic status on PMMA surfaces treated with PMBPAz were observed, indicating the presence of the polymer on the substrates. The treated PMMA surfaces showed significant inhibition of S mutans biofilm formation compared to untreated surfaces. The PMBPAz coating was preserved after water soaking and chemical exposure. In addition, water soaking did not decrease the ability of treated PMMA to inhibit biofilm formation compared to treated PMMA specimens not subjected to water soaking. This study suggests that PMBPAz coating may represent a useful modification to PMMA surfaces for inhibiting denture plaque accumulation.

Effect of early statin therapy after acute coronary syndromes: a concise review of the recent data.

PubMed

Bybee, Kevin A; Wright, R Scott; Kopecky, Stephen L

2002-01-01

HMG Co-A reductase inhibitors(statins) have been shown, in three large randomized trials, to decrease adverse cardiac events in patients with clinically evident coronary artery disease. All of these trials have excluded patients with an acute coronary syndrome within the three months prior to enrollment. Statin therapy is thought to stabilize coronary plaque and decrease the risk of plaque rupture. Statins have been shown to quickly reduce levels of LDL-C in addition to altering systemic inflammatory responses, improving endothelial function, and reducing platelet aggregation and activation. These mechanisms are potentially beneficial in the setting of acute coronary syndromes, a time of profound plaque instability. There is a growing body of evidence supporting the early initiation of statin therapy in the setting of acute coronary syndromes. This paper reviews the available data from randomized-controlled trials and observational studies evaluating the effect of early statin initiation during, or soon following, an acute coronary syndrome.

Blood Flow in Stenotic Carotid Bifurcation

NASA Astrophysics Data System (ADS)

Rayz, Vitaliy L.; Williamson, Shobha Devi; Berger, Stanley A.; Saloner, David

2004-11-01

Mechanical forces induced by blood flow on an arterial wall play an important role in the development and growth of atherosclerotic plaque. To assess vulnerability of a plaque it is important to model the flow in a realistic, patient-specific geometry. Three-dimensional models of stenotic carotid bifurcations were obtained from MR images and grids were generated for the flow domains. The unsteady, incompressible Navier-Stokes equations were solved numerically using physiological boundary conditions. The results obtained by computations were compared with in-vivo ultrasound measurements and flow visualization experiments carried out for the same geometry. The simulations show a high velocity jet forming at the stenotic throat and a strong recirculation zone downstream of the stenosis. The jet grows rapidly during the systolic part of the pulse. During diastole the flow is more stagnant. The flow is highly three-dimensional and unsteady which is clearly demonstrated by the flow streamlines. These unsteady flows cause rapid temporal and spatial changes of the forces acting on the atherosclerotic plaque, which has important effects on its growth and stability.

Plaque bacterial microbiome diversity in children younger than 30 months with or without caries prior to eruption of second primary molars.

PubMed

Xu, He; Hao, Wenjing; Zhou, Qiong; Wang, Wenhong; Xia, Zhongkui; Liu, Chuan; Chen, Xiaochi; Qin, Man; Chen, Feng

2014-01-01

Our primary objective is to phylogenetically characterize the supragingival plaque bacterial microbiome of children prior to eruption of second primary molars by pyrosequencing method for studying etiology of early childhood caries. Supragingival plaque samples were collected from 10 caries children and 9 caries-free children. Plaque DNA was extracted, used to generate DNA amplicons of the V1-V3 hypervariable region of the bacterial 16S rRNA gene, and subjected to 454-pyrosequencing. On average, over 22,000 sequences per sample were generated. High bacterial diversity was noted in the plaque of children with caries [170 operational taxonomical units (OTU) at 3% divergence] and caries-free children (201 OTU at 3% divergence) with no significant difference. A total of 8 phyla, 15 classes, 21 orders, 30 families, 41 genera and 99 species were represented. In addition, five predominant phyla (Firmicute, Fusobacteria, Proteobacteria, Bacteroidetes and Actinobacteria) and seven genera (Leptotrichia, Streptococcus, Actinomyces, Prevotella, Porphyromonas, Neisseria, and Veillonella) constituted a majority of contents of the total microbiota, independent of the presence or absence of caries. Principal Component Analysis (PCA) presented that caries-related genera included Streptococcus and Veillonella; while Leptotrichia, Selenomonas, Fusobacterium, Capnocytophaga and Porphyromonas were more related to the caries-free samples. Neisseria and Prevotella presented approximately in between. In both groups, the degree of shared organism lineages (as defined by species-level OTUs) among individual supragingival plaque microbiomes was minimal. Our study represented for the first time using pyrosequencing to elucidate and monitor supragingival plaque bacterial diversity at such young age with second primary molar unerrupted. Distinctions were revealed between caries and caries-free microbiomes in terms of microbial community structure. We observed differences in abundance for several microbial groups between the caries and caries-free host populations, which were consistent with the ecological plaque hypothesis. Our approach and findings could be extended to correlating microbiomic changes after occlusion establishment and caries treatment.

Ultrastructure and morphology of biofilms on thermoplastic orthodontic appliances in 'fast' and 'slow' plaque formers.

PubMed

Low, Bernard; Lee, Wilson; Seneviratne, C J; Samaranayake, Lakshman P; Hägg, Urban

2011-10-01

The aim of this study was to investigate the morphological features and distribution of biofilms on Invisalign orthodontic appliances, in a sample of 'slow' and 'fast' plaque formers using scanning electron microscopy (SEM). Fifty-six Chinese male/female volunteers (aged 19-39 years) were screened for their plaque-forming rate using the plaque percentage index (PPI) coupled with digital photography and computer-based image analysis, after a period of 48 hours of abstinence from oral hygiene procedures. Eleven volunteers (seven males/four females) representing the lowest and highest ends of the plaque formation spectrum were chosen as slow and fast plaque formers, respectively. The subjects wore a full-coverage splint appliance, in which four tiles of Invisalign material were embedded. These tiles were collected at intervals of 1, 3, 6, 12, 24, and 48 hours, as well as 3, 7, and 14 days, immediately fixed in 10 per cent paraformaldehyde in 0.2 M cacodylate buffer solution and prepared for SEM. The surface configuration of the Invisalign appliance was visualized, as well as the chronological pattern of biofilm formation. Significance between fast and slow plaque formers was determined using a Student's t-test. Colonization appeared to centre initially on the raised edges or textured surfaces of the appliance, and initial adhesion was quicker and more abundant in the fast plaque-forming group. In the later stages of biofilm development, both groups showed no discernible differences in biofilm accrual on the surfaces, but the fast group displayed a more complex biofilm structure. More recessed and sheltered areas of the appliance, such as the cusp tips and attachment dimples, harboured more biofilm than the flat surfaces. Hence, it seems that the novel Invisialign orthodontic appliance is a useful tool to investigate the features of biofilm formation in time-course studies.

Localization of Coronary High-Intensity Signals on T1-Weighted MR Imaging: Relation to Plaque Morphology and Clinical Severity of Angina Pectoris.

PubMed

Matsumoto, Kenji; Ehara, Shoichi; Hasegawa, Takao; Sakaguchi, Mikumo; Otsuka, Kenichiro; Yoshikawa, Junichi; Shimada, Kenei

2015-10-01

This study sought to investigate the relationship between localization of high-intensity signals (HISs) on T1-weighted imaging (T1WI) with the noncontrast magnetic resonance technique and plaque morphology detected on optical coherence tomography, and the clinical severity of angina pectoris. Since the introduction of the T1WI noncontrast magnetic resonance technique for plaque imaging, some groups have reported that HISs in the coronary artery on T1WI are associated with a vulnerable morphology and future cardiac events. However, the association between the localization of HISs, such as coronary intrawall or intraluminal, and plaque morphology has not been investigated. One hundred lesions with either stable or unstable angina were included and divided into 3 groups according to the following criteria using T1WI. First, the plaques with the ratio between the signal intensities of coronary plaque and cardiac muscle ≤1.0 were classified as non-HISs (n = 39). Then, HISs with the ratio between the signal intensities of coronary plaque and cardiac muscle >1.0 were classified into 2 types by using cross-sectional T1WI. Those localized within the coronary wall when the lumen was identified were defined as intrawall HISs (n = 37), whereas those occupying the lumen when the lumen was not, or even if only partly, identified, were defined as intraluminal HISs (n = 24). Multivariate analysis revealed that intrawall HISs were associated with macrophage accumulation and the absence of calcification assessed by using optical coherence tomography. In contrast, thrombus and intimal vasculature were independent factors associated with intraluminal HISs. Furthermore, 50% of patients with intraluminal HISs experienced rest angina, such as Braunwald class II or III. This study shows that intrawall and intraluminal HISs on T1WI in patients with angina are related to the different types of vulnerable plaque morphology and the clinical severity. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Effects of tongue cleaning on bacterial flora in tongue coating and dental plaque: a crossover study

PubMed Central

2014-01-01

Background The effects of tongue cleaning on reconstruction of bacterial flora in dental plaque and tongue coating itself are obscure. We assessed changes in the amounts of total bacteria as well as Fusobacterium nucleatum in tongue coating and dental plaque specimens obtained with and without tongue cleaning. Methods We conducted a randomized examiner-blind crossover study using 30 volunteers (average 23.7 ± 3.2 years old) without periodontitis. After dividing randomly into 2 groups, 1 group was instructed to clean the tongue, while the other did not. On days 1 (baseline), 3, and 10, tongue coating and dental plaque samples were collected after recording tongue coating score (Winkel tongue coating index: WTCI). After a washout period of 3 weeks, the same examinations were performed with the subjects allocated to the alternate group. Genomic DNA was purified from the samples and applied to SYBR® Green-based real-time PCR to quantify the amounts of total bacteria and F. nucleatum. Results After 3 days, the WTCI score recovered to baseline, though the amount of total bacteria in tongue coating was significantly lower as compared to the baseline. In plaque samples, the bacterial amounts on day 3 and 10 were significantly lower than the baseline with and without tongue cleaning. Principal component analysis showed that variations of bacterial amounts in the tongue coating and dental plaque samples were independent from each other. Furthermore, we found a strong association between amounts of total bacteria and F. nucleatum in specimens both. Conclusions Tongue cleaning reduced the amount of bacteria in tongue coating. However, the cleaning had no obvious contribution to inhibit dental plaque formation. Furthermore, recovery of the total bacterial amount induced an increase in F. nucleatum in both tongue coating and dental plaque. Thus, it is recommended that tongue cleaning and tooth brushing should both be performed for promoting oral health. PMID:24423407

Effects of tongue cleaning on bacterial flora in tongue coating and dental plaque: a crossover study.

PubMed

Matsui, Miki; Chosa, Naoyuki; Shimoyama, Yu; Minami, Kentaro; Kimura, Shigenobu; Kishi, Mitsuo

2014-01-14

The effects of tongue cleaning on reconstruction of bacterial flora in dental plaque and tongue coating itself are obscure. We assessed changes in the amounts of total bacteria as well as Fusobacterium nucleatum in tongue coating and dental plaque specimens obtained with and without tongue cleaning. We conducted a randomized examiner-blind crossover study using 30 volunteers (average 23.7 ± 3.2 years old) without periodontitis. After dividing randomly into 2 groups, 1 group was instructed to clean the tongue, while the other did not. On days 1 (baseline), 3, and 10, tongue coating and dental plaque samples were collected after recording tongue coating score (Winkel tongue coating index: WTCI). After a washout period of 3 weeks, the same examinations were performed with the subjects allocated to the alternate group. Genomic DNA was purified from the samples and applied to SYBR® Green-based real-time PCR to quantify the amounts of total bacteria and F. nucleatum. After 3 days, the WTCI score recovered to baseline, though the amount of total bacteria in tongue coating was significantly lower as compared to the baseline. In plaque samples, the bacterial amounts on day 3 and 10 were significantly lower than the baseline with and without tongue cleaning. Principal component analysis showed that variations of bacterial amounts in the tongue coating and dental plaque samples were independent from each other. Furthermore, we found a strong association between amounts of total bacteria and F. nucleatum in specimens both. Tongue cleaning reduced the amount of bacteria in tongue coating. However, the cleaning had no obvious contribution to inhibit dental plaque formation. Furthermore, recovery of the total bacterial amount induced an increase in F. nucleatum in both tongue coating and dental plaque. Thus, it is recommended that tongue cleaning and tooth brushing should both be performed for promoting oral health.

Plaque morphology detected with Duplex ultrasound before carotid angioplasty and stenting (CAS) is not a predictor of carotid artery in-stent restenosis, a case control study.

PubMed

Wasser, Katrin; Karch, André; Gröschel, Sonja; Witzenhausen, Janin; Gröschel, Klaus; Bähr, Mathias; Liman, Jan

2013-11-05

In-stent restenosis (ISR) is an important factor endangering the long-term safety and efficacy of carotid artery angioplasty and stenting (CAS). It is plausible that soft vulnerable plaques are more likely to be injured during CAS procedure and are therefore more likely to initiate the cascade finally leading to ISR. The aim of this study was to investigate if plaque morphology detected by a simple applicable Duplex ultrasound score before CAS can be used as a predictor for ISR. Within a prospectively collected single-centre CAS database of 281 patients (comprising 300 arteries) with high-grade carotid artery stenosis, who underwent CAS between May 2003 and January 2013, we conducted a nested case-control study. Plaque morphology before CAS was analysed by a blinded investigator and each parameter of the Total Plaque Risk Score (TPRS) as well as the whole score was evaluated with regard to its diagnostic validity for ISR. We analysed the data of 10 patients with ISR and 50 patients without ISR. There were no significant differences with respect to baseline characteristics, vascular risk factors, and degree of stenosis between patients with and without ISR. The duration of follow-up was longer in patients with ISR (p = 0.024) and these patients were more likely to show increased PSV (p = 0.012) immediately after CAS than patients without ISR. Neither individual parameters of the TPRS score nor the score as a whole were suitable as a diagnostic test for ISR development. In the present study we could demonstrate that the non-contrast enhanced DUS of the pre-interventional plaque formation cannot be used as a predictor for the development of ISR. Evaluating a more sophisticated, but not routinely available approach e.g. by ultrasound based plaque perfusion imaging or CT based plaque analysis could be helpful in the future in order to assess the role of plaque morphology in the context of ISR development.

Clinical comparison of plaque inhibition effects of a novel stabilized stannous fluoride dentifrice and a chlorhexidine digluconate dentifrice using digital plaque imaging.

PubMed

Bellamy, P G; Boulding, A; Farmer, S; Day, T N; Mussett, A J; Barker, M L

2011-01-01

To compare the plaque inhibition efficacy of a novel 0.454% stannous fluoride (SnF2) test dentifrice with sodium hexametaphosphate and stannous chloride to a chlorhexidine digluconate (0.05%), aluminium lactate (0.8%), and aluminium fluoride marketed control dentifrice (Lacalut Aktiv or AlF3/Chx). This was a randomized, two-treatment, two-period, double-blind crossover study that compared the SnF2 test dentifrice to the AlF3/Chx control dentifrice. Each of the two treatment periods lasted for 17 consecutive days of product use, during which subjects were required to brush twice per day with their assigned dentifrice using a standard manual toothbrush (Oral-B P35 Indicator). The two periods of the crossover were separated by a four-day washout period. Plaque levels on the facial anterior tooth surfaces were evaluated and averaged among three assessment days at the end of each treatment period using digital plaque imaging analysis (DPIA). The evening prior to assessments, subjects only brushed lingual surfaces. Assessment time points were carried out in the morning following no morning brushing (A.M. pre-brush), following 40 seconds of brushing with the assigned dentifrice (A.M. post-brush), and in the afternoon (P.M.). The DPIA captured images were used to calculate and analyze visible plaque coverage. Twenty-eight subjects were randomized and completed the study. At each assessment time point, the SnF2 test dentifrice demonstrated a statistically significant lower plaque level compared to the AlF3/Chx dentifrice: A.M. mean pre-brush 15.9% lower, p < 0.05; A.M. mean post-brush 22.2% lower, p < 0.05; P.M. mean 24.3% lower, p < 0.005. Compared to the AlF3/Chx control dentifrice, the novel SnF2 test dentifrice significantly inhibited plaque regrowth overnight and during the day. Immediately after brushing there was also significantly less plaque coverage with the SnF2 test dentifrice.

Dynamics of the microglial/amyloid interaction indicate a role in plaque maintenance.

PubMed

Bolmont, Tristan; Haiss, Florent; Eicke, Daniel; Radde, Rebecca; Mathis, Chester A; Klunk, William E; Kohsaka, Shinichi; Jucker, Mathias; Calhoun, Michael E

2008-04-16

Microglial cells aggregate around amyloid plaques in Alzheimer's disease, but, despite their therapeutic potential, various aspects of their reactive kinetics and role in plaque pathogenesis remain hypothetical. Through use of in vivo imaging and quantitative morphological measures in transgenic mice, we demonstrate that local resident microglia rapidly react to plaque formation by extending processes and subsequently migrating toward plaques, in which individual transformed microglia somata remain spatially stable for weeks. The number of plaque-associated microglia increased at a rate of almost three per plaque per month, independent of plaque volume. Larger plaques were surrounded by larger microglia, and a subset of plaques changed in size over time, with an increase or decrease related to the volume of associated microglia. Far from adopting a more static role, plaque-associated microglia retained rapid process and membrane movement at the plaque/glia interface. Microglia internalized systemically injected amyloid-binding dye at a much higher rate in the vicinity of plaques. These results indicate a role for microglia in plaque maintenance and provide a model with multiple targets for therapeutic intervention.

Dynamics of the Microglial/Amyloid Interaction Indicate a Role in Plaque Maintenance

PubMed Central

Bolmont, Tristan; Haiss, Florent; Eicke, Daniel; Radde, Rebecca; Mathis, Chester A.; Klunk, William E.; Kohsaka, Shinichi; Jucker, Mathias

2008-01-01

Microglial cells aggregate around amyloid plaques in Alzheimer's disease, but, despite their therapeutic potential, various aspects of their reactive kinetics and role in plaque pathogenesis remain hypothetical. Through use of in vivo imaging and quantitative morphological measures in transgenic mice, we demonstrate that local resident microglia rapidly react to plaque formation by extending processes and subsequently migrating toward plaques, in which individual transformed microglia somata remain spatially stable for weeks. The number of plaque-associated microglia increased at a rate of almost three per plaque per month, independent of plaque volume. Larger plaques were surrounded by larger microglia, and a subset of plaques changed in size over time, with an increase or decrease related to the volume of associated microglia. Far from adopting a more static role, plaque-associated microglia retained rapid process and membrane movement at the plaque/glia interface. Microglia internalized systemically injected amyloid-binding dye at a much higher rate in the vicinity of plaques. These results indicate a role for microglia in plaque maintenance and provide a model with multiple targets for therapeutic intervention. PMID:18417708

Differences in subclinical cardiovascular disease between African American and Caucasian women with systemic lupus erythematosus.

PubMed

Rhew, Elisa Y; Manzi, Susan M; Dyer, Alan R; Kao, Amy H; Danchenko, Natalya; Barinas-Mitchell, Emma; Sutton-Tyrrell, Kim; McPherson, David D; Pearce, William; Edmundowicz, Daniel; Kondos, George T; Ramsey-Goldman, Rosalind

2009-02-01

Racial differences exist in disease rates and mortality in both cardiovascular disease (CVD) and systemic lupus erythematosus (SLE). The objective of this cross-sectional study was to compare the frequency and risk factors for subclinical CVD in African American (AA) and Caucasian women with SLE and no prior CVD events. Traditional CVD risk factors and SLE-related factors were assessed in 309 SLE women. Subclinical CVD was assessed by carotid ultrasound to measure intimamedial thickness (IMT) and plaque, and electron beam computed tomography (EBCT) was used to measure coronary artery calcium (CAC). AA women had less education and higher levels of body mass index, blood pressure, lipoprotein(a), C-reactive protein (CRP), fibrinogen, and erythrocyte sedimentation rate (ESR). However, AA women had lower albumin, more and longer duration of corticosteroid use, higher SLE disease activity and damage, and more dsDNA antibodies compared with Caucasian women after adjustment for age and study site. More AA women had carotid plaque (adjusted odds ratio [OR], 1.94; 95% confidence interval [CI], 1.03-3.65) and higher carotid IMT (0.620 vs 0.605 mm, P = 0.07) but similar CAC compared with Caucasians. A multivariate analysis revealed that the following risk factor variables were significantly different between the racial groups and associated with plaque: blood pressure, current corticosteroid use, SLE disease activity, and SLE damage. All factors contributed to the result, but no individual risk factor fully accounted for the association between race and plaque. In conclusion, the presence of carotid plaque was higher in AA compared with Caucasian women with SLE, in contrast to studies of non-SLE subjects, in which AA have similar or less plaque than Caucasians. A combination of SLE-related and traditional CVD risk factors explained the racial difference in plaque burden.

Differences in Subclinical Cardiovascular Disease between African American and Caucasian Women with Systemic Lupus Erythematosus

PubMed Central

Rhew, Elisa Y.; Manzi, Susan M.; Dyer, Alan R.; Kao, Amy H.; Danchenko, Natalya; Barinas-Mitchell, Emma; Sutton-Tyrrell, Kim; McPherson, David D.; Pearce, William; Edmundowicz, Daniel; Kondos, George T.; Ramsey-Goldman, Rosalind

2009-01-01

Racial differences exist in disease rates and mortality in both cardiovascular disease (CVD) and Systemic Lupus Erythematosus (SLE). The objective of this cross-sectional study was to compare the frequency of and risk factors for subclinical CVD in African-American (AA) and Caucasian women with SLE and no prior CVD events. Traditional CVD risk factors and SLE-related factors were assessed in 309 SLE women. Subclinical CVD was assessed by carotid ultrasound to measure intima-medial thickness (IMT) and plaque, and electron beam computed tomography (EBCT) to measure coronary artery calcium (CAC). AA had less education, higher body mass index, blood pressure, lipoprotein(a), CRP, fibrinogen, and ESR, but lower albumin; more and longer duration of corticosteroid use; higher SLE disease activity and damage; and more had dsDNA antibodies compared to Caucasian women, after adjustment for age and study-site. More AA had carotid plaque (adjusted OR 1.94, 95%CI 1.03, 3.65) and higher carotid IMT (0.620 vs. 0.605mm, p=0.07) compared with Caucasians, but similar CAC. Multivariate analysis included risk factor variables significantly different between the racial groups and associated with plaque: blood pressure, current corticosteroid use, SLE disease activity and damage. All factors contributed, but no individual risk factor fully accounted for the association between race and plaque. In conclusion, the presence of carotid plaque was higher in AA compared with Caucasian women with SLE, in contrast to studies of non-SLE subjects, where AA have similar or less plaque than Caucasians. A combination of SLE-related and traditional CVD risk factors explained the racial difference in plaque burden. PMID:19138649

[Analysis of organic acids in human dental plaque by means of gas chromatography/mass spectrometry].

PubMed

Li, J; Dai, C; Zhou, X; Xiang, Z; Chen, H

1999-09-01

The purpose of this study was to investigate the composition of plaque fatty acids in the healthy population. The study was made on 10 volunteers over the age of 18 who were divided into three sub-groups (3-4 individuals). Neither subject exhibited clinical evidence of salivary gland disorder and any medication affecting salivary functions were not used. A sensitive GC/MS method with VG7070E mass spectrometer was developed in our study. The sample separation was carried out on a fused silica capillary column with OV-1. The column size was 23 m x 0.23 mm. The temperature program was as follows: from 40 degrees C to 120 degrees C fast, then from 120 degrees C to 240 degrees C at 6 degrees C/min. The results showed that there were 14 organic acids and isomers present in plaque. They were C12:0, C14:0, C15:0, C16:0, C16:1, C18:0, C18:1, C18:2, C20:0 and phenylacetic acid, phenylpropionic acid. The higher content of fatty acids in the sample were C16:0, C18:0, and C18:1. The aromatic acids were detected only in some samples. The odd-numbers fatty acids and aromatic acids were for the first time detected. The origin of organic acids in plaque is an ongoing area of research. Our data clearly identify the bacterial contribution to the organic acids of plaque matrix, which may have a special relationship with bacteria metabolism. The research will help us to understand fatty acids metabolism of dental plaque and to determine their role in the microbial homeostasis of dental plaque.

Effects of plaque lengths on stent surface roughness.

PubMed

Syaifudin, Achmad; Takeda, Ryo; Sasaki, Katsuhiko

2015-01-01

The physical properties of the stent surface influence the effectiveness of vascular disease treatment after stent deployment. During the expanding process, the stent acquires high-level deformation that could alter either its microstructure or the magnitude of surface roughness. This paper constructed a finite element simulation to observe the changes in surface roughness during the stenting process. Structural transient dynamic analysis was performed using ANSYS, to identify the deformation after the stent is placed in a blood vessel. Two types of bare metal stents are studied: a Palmaz type and a Sinusoidal type. The relationship between plaque length and the changes in surface roughness was investigated by utilizing three different length of plaque; plaque length longer than the stent, shorter than the stent and the same length as the stent. In order to reduce computational time, 3D cyclical and translational symmetry was implemented into the FE model. The material models used was defined as a multilinear isotropic for stent and hyperelastic for the balloon, plaque and vessel wall. The correlation between the plastic deformation and the changes in surface roughness was obtained by intermittent pure tensile test using specimen whose chemical composition was similar to that of actual stent material. As the plastic strain is achieved from FE simulation, the surface roughness can be assessed thoroughly. The study found that the plaque size relative to stent length significantly influenced the critical changes in surface roughness. It was found that the length of stent which is equal to the plaque length was preferable due to the fact that it generated only moderate change in surface roughness. This effect was less influential to the Sinusoidal stent.

Lens ion homeostasis relies on the assembly and/or stability of large connexin 46 gap junction plaques on the broad sides of differentiating fiber cells

PubMed Central

Cheng, Catherine; Nowak, Roberta B.; Gao, Junyuan; Sun, Xiurong; Biswas, Sondip K.; Lo, Woo-Kuen; Mathias, Richard T.

2015-01-01

The eye lens consists of layers of tightly packed fiber cells, forming a transparent and avascular organ that is important for focusing light onto the retina. A microcirculation system, facilitated by a network of gap junction channels composed of connexins 46 and 50 (Cx46 and Cx50), is hypothesized to maintain and nourish lens fiber cells. We measured lens impedance in mice lacking tropomodulin 1 (Tmod1, an actin pointed-end capping protein), CP49 (a lens-specific intermediate filament protein), or both Tmod1 and CP49. We were surprised to find that simultaneous loss of Tmod1 and CP49, which disrupts cytoskeletal networks in lens fiber cells, results in increased gap junction coupling resistance, hydrostatic pressure, and sodium concentration. Protein levels of Cx46 and Cx50 in Tmod1−/−;CP49−/− double-knockout (DKO) lenses were unchanged, and electron microscopy revealed normal gap junctions. However, immunostaining and quantitative analysis of three-dimensional confocal images showed that Cx46 gap junction plaques are smaller and more dispersed in DKO differentiating fiber cells. The localization and sizes of Cx50 gap junction plaques in DKO fibers were unaffected, suggesting that Cx46 and Cx50 form homomeric channels. We also demonstrate that gap junction plaques rest in lacunae of the membrane-associated actin-spectrin network, suggesting that disruption of the actin-spectrin network in DKO fibers may interfere with gap junction plaque accretion into micrometer-sized domains or alter the stability of large plaques. This is the first work to reveal that normal gap junction plaque localization and size are associated with normal lens coupling conductance. PMID:25740157

Metal ions differentially influence the aggregation and deposition of Alzheimer's beta-amyloid on a solid template.

PubMed

Ha, Chanki; Ryu, Jungki; Park, Chan Beum

2007-05-22

The abnormal deposition and aggregation of beta-amyloid (Abeta) on brain tissues are considered to be one of the characteristic neuropathological features of Alzheimer's disease (AD). Environmental conditions such as metal ions, pH, and cell membranes are associated with Abeta deposition and plaque formation. According to the amyloid cascade hypothesis of AD, the deposition of Abeta42 oligomers as diffuse plaques in vivo is an important earliest event, leading to the formation of fibrillar amyloid plaques by the further accumulation of soluble Abeta under certain environmental conditions. In order to characterize the effect of metal ions on amyloid deposition and plaque growth on a solid surface, we prepared a synthetic template by immobilizing Abeta oligomers onto a N-hydroxysuccinimide ester-activated solid surface. According to our study using ex situ atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FT-IR), and thioflavin T (ThT) fluorescence spectroscopy, Cu2+ and Zn2+ ions accelerated both Abeta40 and Abeta42 deposition but resulted only in the formation of "amorphous" aggregates. In contrast, Fe3+ induced the deposition of "fibrillar" amyloid plaques at neutral pH. Under mildly acidic environments, the formation of fibrillar amyloid plaques was not induced by any metal ion tested in this work. Using secondary ion mass spectroscopy (SIMS) analysis, we found that binding Cu ions to Abeta deposits on a solid template occurred by the possible reduction of Cu ions during the interaction of Abeta with Cu2+. Our results may provide insights into the role of metal ions on the formation of fibrillar or amorphous amyloid plaques in AD.

Lens ion homeostasis relies on the assembly and/or stability of large connexin 46 gap junction plaques on the broad sides of differentiating fiber cells.

PubMed

Cheng, Catherine; Nowak, Roberta B; Gao, Junyuan; Sun, Xiurong; Biswas, Sondip K; Lo, Woo-Kuen; Mathias, Richard T; Fowler, Velia M

2015-05-15

The eye lens consists of layers of tightly packed fiber cells, forming a transparent and avascular organ that is important for focusing light onto the retina. A microcirculation system, facilitated by a network of gap junction channels composed of connexins 46 and 50 (Cx46 and Cx50), is hypothesized to maintain and nourish lens fiber cells. We measured lens impedance in mice lacking tropomodulin 1 (Tmod1, an actin pointed-end capping protein), CP49 (a lens-specific intermediate filament protein), or both Tmod1 and CP49. We were surprised to find that simultaneous loss of Tmod1 and CP49, which disrupts cytoskeletal networks in lens fiber cells, results in increased gap junction coupling resistance, hydrostatic pressure, and sodium concentration. Protein levels of Cx46 and Cx50 in Tmod1(-/-);CP49(-/-) double-knockout (DKO) lenses were unchanged, and electron microscopy revealed normal gap junctions. However, immunostaining and quantitative analysis of three-dimensional confocal images showed that Cx46 gap junction plaques are smaller and more dispersed in DKO differentiating fiber cells. The localization and sizes of Cx50 gap junction plaques in DKO fibers were unaffected, suggesting that Cx46 and Cx50 form homomeric channels. We also demonstrate that gap junction plaques rest in lacunae of the membrane-associated actin-spectrin network, suggesting that disruption of the actin-spectrin network in DKO fibers may interfere with gap junction plaque accretion into micrometer-sized domains or alter the stability of large plaques. This is the first work to reveal that normal gap junction plaque localization and size are associated with normal lens coupling conductance. Copyright © 2015 the American Physiological Society.

Genetic susceptibility for Alzheimer disease neuritic plaque pathology.

PubMed

Shulman, Joshua M; Chen, Kewei; Keenan, Brendan T; Chibnik, Lori B; Fleisher, Adam; Thiyyagura, Pradeep; Roontiva, Auttawut; McCabe, Cristin; Patsopoulos, Nikolaos A; Corneveaux, Jason J; Yu, Lei; Huentelman, Matthew J; Evans, Denis A; Schneider, Julie A; Reiman, Eric M; De Jager, Philip L; Bennett, David A

2013-09-01

While numerous genetic susceptibility loci have been identified for clinical Alzheimer disease (AD), it is important to establish whether these variants are risk factors for the underlying disease pathology, including neuritic plaques. To investigate whether AD susceptibility loci from genome-wide association studies affect neuritic plaque pathology and to additionally identify novel risk loci for this trait. Candidate analysis of single-nucleotide polymorphisms and genome-wide association study in a joint clinicopathologic cohort, including 725 deceased subjects from the Religious Orders Study and the Rush Memory and Aging Project (2 prospective, community-based studies), followed by targeted validation in an independent neuroimaging cohort, including 114 subjects from multiple clinical and research centers. A quantitative measure of neuritic plaque pathologic burden, based on assessments of silver-stained tissue averaged from multiple brain regions. Validation based on β-amyloid load by immunocytochemistry, and replication with fibrillar β-amyloid positron emission tomographic imaging with Pittsburgh Compound B or florbetapir. Besides the previously reported APOE and CR1 loci, we found that the ABCA7 (rs3764650; P = .02) and CD2AP (rs9349407; P = .03) AD susceptibility loci are associated with neuritic plaque burden. In addition, among the top results of our genome-wide association study, we discovered a novel variant near the amyloid precursor protein gene (APP, rs2829887) that is associated with neuritic plaques (P = 3.3 × 10-6). This polymorphism was associated with postmortem β-amyloid load as well as fibrillar β-amyloid in 2 independent cohorts of adults with normal cognition. These findings enhance understanding of AD risk factors by relating validated susceptibility alleles to increased neuritic plaque pathology and implicate common genetic variation at the APP locus in the earliest, presymptomatic stages of AD.

Rationale and design of the PREDICT (Plaque Registration and Evaluation Detected In Computed Tomography) registry.

PubMed

Yamamoto, Hideya; Awai, Kazuo; Kuribayashi, Sachio; Kihara, Yasuki

2014-01-01

At least two-thirds of cases of acute coronary syndrome are caused by disruption of an atherosclerotic plaque. The natural history of individual plaques is unknown and needs to be established. The Plaque Registration and Evaluation Detected In Computed Tomography (PREDICT) registry is a prospective, multicenter, longitudinal, observational registry. This registry was designed to examine the relationships among coronary CT angiography (CTA) findings and clinical findings, mortality, and morbidity. The relationships among progression of coronary atherosclerosis, including changes in plaque characteristics on coronary CTA, and serum lipid levels and modification of coronary risk factors will also be evaluated. From October 2009 to December 2012, 3015 patients who underwent coronary CTA in 29 centers in Japan were enrolled. These patients were followed for 2 years. The primary end points were considered as all-cause mortality and major cardiac events, including cardiac death, nonfatal myocardial infarction, and unstable angina that required hospitalization. The secondary end points were heart failure that required administration of diuretics, target vessel revascularization, cerebral infarction, peripheral arterial disease, and invasive coronary angiography. Blood pressure, serum lipid, and C-reactive protein levels and all cardiovascular events were recorded at 1 and 2 years. If the initial coronary CTA showed any stenosis or plaques, follow-up coronary CTA was scheduled at 2 years to determine changes in coronary lesions, including changes in plaque characteristics. Analysis of the PREDICT registry data will clarify the relationships between coronary CTA findings and cardiovascular mortality and morbidity in a collaborative multicenter fashion. This trial is registered at www.clinicaltrials.gov as NCT 00991835. Copyright © 2014 Society of Cardiovascular Computed Tomography. All rights reserved.

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

Aryal, P; Molloy, JA; Rivard, MJ

Purpose: To investigate the effect of plaque design and radionuclides on eye plaque dosimetry. Methods: The Monte Carlo N-particle Code version 6 (MCNP6) was used for radiation transport simulations. The 14 mm and 16 mm diameter COMS plaques and the model EP917 plaque were simulated using brachytherapy seeds containing I-125, Pd-103, and Cs-131 radionuclides. The origin was placed at the scleral inner surface. The central axis (CAX) doses of both COMS plaques at −1 mm, 0 mm, 1 mm, 2 mm, 5 mm, 10 mm, 15 mm, 20 mm, and 22.6 mm were compared to the model EP917 plaque. Dosemore » volume histograms (DVHs) were also created for both COMS plaques for the tumor and outer sclera then compared to results for the model EP917 plaque. Results: For all radionuclides, the EP917 plaque delivered higher dose (max 343%) compared to the COMS plaques, except for the 14 mm COMS plaque with Cs-131 at 1 mm and 2 mm depths from outer sclera surface. This could be due to source design. For all radionuclides, the 14 mm COMS plaque delivered higher doses compared to the 16 mm COMS plaque for the depths up to 5 mm. Dose differences were not significant beyond depths of 10 mm due to ocular lateral scatter for the different plaque designs. Tumor DVHs for the 16 mm COMS plaque with Cs-131 provided better dose homogeneity and conformity compared to other COMS plaques with I-125 and Pd-103. Using Pd-103, DVHs for the 16 mm COMS plaque delivered less dose to outer sclera compared to other plaques. Conclusion: This study identified improved tumor homogeneity upon considering radionuclides and plaque designs, and found that scleral dose with the model EP917 plaque was higher than for the 16 mm COMS plaque for all the radionuclides studied.« less

Mesenchymal Stem Cells Stabilize Atherosclerotic Vulnerable Plaque by Anti-Inflammatory Properties.

PubMed

Wang, Shuang-shuang; Hu, Si-wang; Zhang, Qing-hua; Xia, Ai-xiang; Jiang, Zhi-xin; Chen, Xiao-min

2015-01-01

Formation and progression of atherosclerotic vulnerable plaque (VP) is the primary cause of many cardio-cerebrovascular diseases such as acute coronary syndrome and stroke. It has been reported that bone marrow mesenchymal stem cells (MSC) exhibit protective effects against many kinds of diseases including myocardial infarction. Here, we examined the effects of intravenous MSC infusion on a VP model and provide novel evidence of its influence as a therapy in this animal disease model. Thirty healthy male New Zealand white rabbits were randomly divided into a MSC, VP or stable plaque (SP) group (n = 10/group) and received high fat diet and cold-induced common carotid artery intimal injury with liquid nitrogen to form atherosclerotic plaques. Serum hs-CRP, TNF-α, IL-6 and IL-10 levels were measured by ELISA at 1, 2, 3, 7, 14, 21 and 28 days after MSC transplantation. The animals were sacrificed at 4 weeks after MSC transplantation. Lesions in the right common carotid were observed using H&E and Masson staining, and the fibrous cap/lipid core ratio of atherosclerotic plaques were calculated. The expression of nuclear factor κB (NF-κB) and matrix metalloproteinase 1, 2, 9 (MMP-1,2,9) in the plaque were detected using immunohistochemistry, and apoptotic cells in the plaques were detected by TUNEL. In addition, the level of TNF-α stimulated gene/protein 6 (TSG-6) mRNA and protein were measured by quantitative Real-Time PCR and Western blotting, respectively. Two rabbits in the VP group died of lung infection and cerebral infarction respectively at 1 week after plaque injury by liquid nitrogen. Both H&E and Masson staining revealed that the plaques from the SP and MSC groups had more stable morphological structure and a larger fibrous cap/lipid core ratio than the VP group. Serum hs-CRP, TNF-α and IL-6 were significantly down-regulated, whereas IL-10 was significantly up-regulated in the MSC group compared with the VP group. .Immunohistochemistry analysis revealed that NF-κB and MMP expression was reduced in the MSC and SP groups compared to the VP group. Cell apoptosis decreased significantly in both the MSC and SP groups in comparison to the VP group. TSG-6 mRNA and protein expression were higher in the plaques of the MSC group compared to the VP and SP groups. Our study results suggest that MSC transplantation can effectively stabilize vulnerable plaques in atherosclerotic rabbits. This may potentially offer a new clinical application of MSC in atherosclerosis.

Experimental design

NASA Technical Reports Server (NTRS)

Lim, H. S.

1983-01-01

The design of long life, low weight nickel cadmium cells is studied. The status of a program to optimize nickel electrodes for the best performance is discussed. The pore size of the plaque, the mechanical strength and active material loading are considered in depth.

Topographic association of angioscopic yellow plaques with coronary atherosclerotic plaque: assessment with quantitative colorimetry in human coronary artery autopsy specimens.

PubMed

Ishibashi, Fumiyuki; Lisauskas, Jennifer B; Kawamura, Akio; Waxman, Sergio

2008-01-01

Yellow plaques seen during coronary angioscopy are thought to be the surrogates for superficial intimal lipids in coronary plaque. Given diffuse and heterogeneous nature of atherosclerosis, yellow plaques in coronaries may be seen as several yellow spots on diffuse coronary plaque. We examined the topographic association of yellow plaques with coronary plaque. In 40 non-severely stenotic ex-vivo coronary segments (average length: 52.2 +/- 3.1 mm), yellow plaques were examined by angioscopy with quantitative colorimetry. The segments were cut perpendicular to the long axis of the vessel at 2 mm intervals, and 1045 slides with 5 microm thick tissue for whole segments were prepared. To construct the plaque surface, each tissue slice was considered to be representative of the adjacent 2 mm. The circumference of the lumen and the lumen border of plaque were measured in each slide, and the plaque surface region was constructed. Coronary plaque was in 37 (93%) of 40 segments, and consisted of a single mass [39.9 +/- 3.9 (0-100) mm, 311.3 +/- 47.4 (0.0-1336.2) mm2]. In 30 (75%) segments, multiple (2-9) yellow plaques were detected on a mass of coronary plaque. The number of yellow plaques correlated positively with coronary plaque surface area (r = 0.77, P < 0.0001). Yellow plaques in coronaries detected by angioscopy with quantitative colorimetry, some of them are associated with lipid cores underneath thin fibrous caps, may be used to assess the extent of coronary plaque. Further research using angioscopy could be of value to study the association of high-risk coronaries with acute coronary syndromes.

Comparison of frequency of calcified versus non-calcified coronary lesions by computed tomographic angiography in patients with stable versus unstable angina pectoris.

PubMed

Meijs, Matthijs F L; Meijboom, W Bob; Bots, Michiel L; Kyrzopoulos, Stamatis; Eu, Rick Neoh; Prokop, Mathias; Doevendans, Pieter A; de Feyter, Pim J; Cramer, Maarten J

2009-08-01

Computed tomographic coronary angiography (CTCA) can noninvasively identify calcified and noncalcified coronary plaques. The aim of this study was to compare the phenotypes of all plaques and of culprit plaques between patients with unstable angina pectoris (UAP) and those with stable angina pectoris (SAP), because plaque characteristics may differ between these patients. In 110 patients with UAP and 189 with SAP from a multicenter study comparing 64-slice CTCA with conventional coronary angiography, the number and phenotypes (noncalcified, mixed, and calcified) of coronary plaques were compared. In a subanalysis in 50 patients with UAP and 64 with SAP, culprit plaque characteristics, including culprit plaque cross-sectional area relative to total vessel cross-sectional area, culprit plaque length, remodeling index, and spotty calcification, were determined. Odds ratios for the presence of UAP, adjusted for clinical variables and the total number of plaques, were calculated for plaque characteristics on CTCA. Although the number of plaques was similar for patients with UAP and those with SAP, plaques in patients with UAP were more frequently noncalcified than in patients with SAP. The odds ratio for UAP was 1.3 (95% confidence interval [CI] 1.1 to 1.5) per noncalcified plaque. In the culprit plaque subanalysis, odds ratios for UAP were 0.99 (95% CI 0.96 to 1.01) per millimeter culprit plaque length, 2.7 (95% CI 1.2 to 6.4) for noncalcified culprit plaque, and 1.06 (95% CI 0.99 to 1.13) per percentage relative culprit plaque cross-sectional area. No significant relation was found between remodeling index or spotty calcification and UAP. In conclusion, noncalcified plaques and large noncalcified culprit plaques are more frequently found in patients with UAP than in those with SAP.

Primary prevention of peri-implantitis: managing peri-implant mucositis.

PubMed

Jepsen, Søren; Berglundh, Tord; Genco, Robert; Aass, Anne Merete; Demirel, Korkud; Derks, Jan; Figuero, Elena; Giovannoli, Jean Louis; Goldstein, Moshe; Lambert, France; Ortiz-Vigon, Alberto; Polyzois, Ioannis; Salvi, Giovanni E; Schwarz, Frank; Serino, Giovanni; Tomasi, Cristiano; Zitzmann, Nicola U

2015-04-01

Over the past decades, the placement of dental implants has become a routine procedure in the oral rehabilitation of fully and partially edentulous patients. However, the number of patients/implants affected by peri-implant diseases is increasing. As there are--in contrast to periodontitis--at present no established and predictable concepts for the treatment of peri-implantitis, primary prevention is of key importance. The management of peri-implant mucositis is considered as a preventive measure for the onset of peri-implantitis. Therefore, the remit of this working group was to assess the prevalence of peri-implant diseases, as well as risks for peri-implant mucositis and to evaluate measures for the management of peri-implant mucositis. Discussions were informed by four systematic reviews on the current epidemiology of peri-implant diseases, on potential risks contributing to the development of peri-implant mucositis, and on the effect of patient and of professionally administered measures to manage peri-implant mucositis. This consensus report is based on the outcomes of these systematic reviews and on the expert opinion of the participants. Key findings included: (i) meta-analysis estimated a weighted mean prevalence for peri-implant mucositis of 43% (CI: 32-54%) and for peri-implantitis of 22% (CI: 14-30%); (ii) bleeding on probing is considered as key clinical measure to distinguish between peri-implant health and disease; (iii) lack of regular supportive therapy in patients with peri-implant mucositis was associated with increased risk for onset of peri-implantitis; (iv) whereas plaque accumulation has been established as aetiological factor, smoking was identified as modifiable patient-related and excess cement as local risk indicator for the development of peri-implant mucositis; (v) patient-administered mechanical plaque control (with manual or powered toothbrushes) has been shown to be an effective preventive measure; (vi) professional intervention comprising oral hygiene instructions and mechanical debridement revealed a reduction in clinical signs of inflammation; (vii) adjunctive measures (antiseptics, local and systemic antibiotics, air-abrasive devices) were not found to improve the efficacy of professionally administered plaque removal in reducing clinical signs of inflammation. Consensus was reached on recommendations for patients with dental implants and oral health care professionals with regard to the efficacy of measures to manage peri-implant mucositis. It was particularly emphasized that implant placement and prosthetic reconstructions need to allow proper personal cleaning, diagnosis by probing and professional plaque removal. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

p62-enriched inclusion bodies in macrophages protect against atherosclerosis

PubMed Central

Sergin, Ismail; Bhattacharya, Somashubhra; Emanuel, Roy; Esen, Emel; Stokes, Carl J.; Evans, Trent D.; Arif, Batool; Curci, John A.; Razani, Babak

2016-01-01

Autophagy is a catabolic cellular mechanism that degrades dysfunctional proteins and organelles. Atherosclerotic plaque formation is enhanced in mice with macrophages that cannot undergo autophagy because of a deficiency of an autophagy component such as ATG5. We showed that exposure of macrophages to atherogenic lipids led to an increase in the abundance of the autophagy chaperone p62, which colocalized with polyubiquitinated proteins in cytoplasmic inclusions. p62 accumulation was increased in ATG5-null macrophages, which had large cytoplasmic ubiquitin-positive p62 inclusions. Aortas from atherosclerotic mice and plaques from human endarterectomy samples showed increased abundance of p62 and polyubiquitinated proteins that co-localized with plaque macrophages, suggesting that p62-enriched protein aggregates were characteristic of atherosclerosis. The formation of the cytoplasmic inclusions depended on p62 because lipid-loaded p62-null macrophages accumulated polyubiquitinated proteins in a diffuse cytoplasmic pattern. The failure of these aggregates to form was associated with increased secretion of IL-1β and enhanced macrophage apoptosis, which depended on the p62 ubiquitin-binding domain and at least partly involved p62-mediated clearance of NLRP3 inflammasomes. Consistent with our in vitro observations, p62-deficient mice formed greater numbers of more complex atherosclerotic plaques, and p62 deficiency further increased atherosclerotic plaque burden in mice with a macrophage-specific ablation of ATG5. Together, these data suggested that sequestration of cytotoxic ubiquitinated proteins by p62 protects against atherogenesis, a condition in which the clearance of protein aggregates is disrupted. PMID:26732762

A rotational ablation tool for calcified atherosclerotic plaque removal.

PubMed

Kim, Min-Hyeng; Kim, Hyung-Jung; Kim, Nicholas N; Yoon, Hae-Sung; Ahn, Sung-Hoon

2011-12-01

Atherosclerosis is a major cardiovascular disease involving accumulations of lipids, white blood cells, and other materials on the inside of artery walls. Since the calcification found in the advanced stage of atherosclerosis dramatically enhances the mechanical properties of the plaque, restoring the original lumen of the artery remains a challenge. High-speed rotational atherectomy, when performed with an ablating grinder to remove the plaque, produces much better results in the treatment of calcified plaque compared to other methods. However, the high-speed rotation of the Rotablator commercial rotational atherectomy device produces microcavitation, which should be avoided because of the serious complications it can cause. This research involves the development of a high-speed rotational ablation tool that does not generate microcavitation. It relies on surface modification to achieve the required surface roughness. The surface roughness of the tool for differential cutting was designed based on lubrication theory, and the surface of the tool was modified using Nd:YAG laser beam engraving. Electron microscope images and profiles indicated that the engraved surface of the tool had approximately 1 μm of root mean square surface roughness. The ablation experiment was performed on hydroxyapatite/polylactide composite with an elastic modulus similar to that of calcified plaque. In addition, differential cutting was verified on silicone rubber with an elastic modulus similar to that of a normal artery. The tool performance and reliability were evaluated by measuring the ablation force exerted, the size of the debris generated during ablation, and through visual inspection of the silicone rubber surface.

Microstructures of Randall's plaques and their interfaces with calcium oxalate monohydrate kidney stones reflect underlying mineral precipitation mechanisms.

PubMed

Sethmann, Ingo; Wendt-Nordahl, Gunnar; Knoll, Thomas; Enzmann, Frieder; Simon, Ludwig; Kleebe, Hans-Joachim

2017-06-01

Randall's plaques (RP) are preferred sites for the formation of calcium oxalate monohydrate (COM) kidney stones. However, although processes of interstitial calcium phosphate (CaP) plaque formation are not well understood, the potential of plaque microstructures as indicators of CaP precipitation conditions received only limited attention. We investigated RP-associated COM stones for structural details of the calcified tissues and microstructural features of plaque-stone interfaces as indicators of the initial processes of stone formation. Significantly increased CaP supersaturation can be expected for interstitial fluid, if reabsorbed ions from the tubular system continuously diffuse into the collagenous connective tissue. Densely packed, fine-grained CaP particles were found in dense textures of basement membranes while larger, laminated particles were scattered in coarse-meshed interstitial tissue, which we propose to be due to differential spatial confinements and restrictions of ion diffusion. Particle morphologies suggest an initial precipitation as metastable amorphous calcium phosphate (ACP). Morphologies and arrangements of first COM crystals at the RP-stone interface ranged from stacked euhedral platelets to skeletal morphologies and even porous, dendritic structures, indicating, in this order, increasing levels of COM supersaturation. Furthermore, these first COM crystals were often coated with CaP. On this basis, we propose that ions from CaP-supersaturated interstitial fluid may diffuse through porous RP into the urine, where a resulting local increase in COM supersaturation could trigger crystal nucleation and, hence, initiate stone formation. Ion-depleted fluid in persistent pores of initial COM layers may get replenished from interstitial fluid, leading to CaP precipitation in porous COM.

Study design and rationale of "Synergistic Effect of Combination Therapy with Cilostazol and ProbUcol on Plaque Stabilization and Lesion REgression (SECURE)" study: a double-blind randomised controlled multicenter clinical trial

PubMed Central

2011-01-01

Background Probucol, a cholesterol-lowering agent that paradoxically also lowers high-density lipoprotein cholesterol has been shown to prevent progression of atherosclerosis. The antiplatelet agent cilostazol, which has diverse antiatherogenic properties, has also been shown to reduce restenosis in previous clinical trials. Recent experimental studies have suggested potential synergy between probucol and cilostazol in preventing atherosclerosis, possibly by suppressing inflammatory reactions and promoting cholesterol efflux. Methods/design The Synergistic Effect of combination therapy with Cilostazol and probUcol on plaque stabilization and lesion REgression (SECURE) study is designed as a double-blind, randomised, controlled, multicenter clinical trial to investigate the effect of cilostazol and probucol combination therapy on plaque volume and composition in comparison with cilostazol monotherapy using intravascular ultrasound and Virtual Histology. The primary end point is the change in the plaque volume of index intermediate lesions between baseline and 9-month follow-up. Secondary endpoints include change in plaque composition, neointimal growth after implantation of stents at percutaneous coronary intervention target lesions, and serum levels of lipid components and biomarkers related to atherosclerosis and inflammation. A total of 118 patients will be included in the study. Discussion The SECURE study will deliver important information on the effects of combination therapy on lipid composition and biomarkers related to atherosclerosis, thereby providing insight into the mechanisms underlying the prevention of atherosclerosis progression by cilostazol and probucol. Trial registration number ClinicalTrials (NCT): NCT01031667 PMID:21226953

Does the presence of the Helicobacter pylori in the dental plaque associate with its gastric infection? A meta-analysis and systematic review.

PubMed

Navabi, Nader; Aramon, Moein; Mirzazadeh, Ali

2011-10-01

There is a great deal of studies on the relationship between the existence of Helicobacter pylori (H. pylori) in oral cavity (dental plaque) and in stomach of patients, with conflicting results worldwide. The purpose of this study was to systematically review the existing litreature to assess if the dental plaque could be a source of gastric H. pylori infection and to explore the source of heterogeneity around it. We searched all the papers published since 2000 on international (Medline, ISI, Embase) databases using standard keywords. Two researchers evaluated the articles with standard critical appraisal form independently and those articles with the quality acquired greater than 70% were included in the study. The combined results were calculated with weighted average and the source of hetrogeneity was tested by meta-regression (random) model. Finally, 23 studies were included (1861 patients). The prevalence of co-infection of gastric and dental plaque H. pylori was 49.7% (95% CI 16-83.4%) and the percent of agreement between the dental plaque H. pylori status and the gastric H. pylori was estimated as 82%. Only one study has reported that dental treatment has a preventive effect on the recurrence of gastric H. pylori infection. Co-infection of gastric H. pylori and dental plaque is reported by half of the studies. However, there is not enough evidence for the efficacy of dental treatment on prevention of recurrent gastric H. pylori infection.

Community-level assessment of dental plaque bacteria susceptibility to triclosan over 19 years.

PubMed

Haraszthy, Violet I; Sreenivasan, Prem K; Zambon, Joseph J

2014-06-02

Triclosan is a broad-spectrum antimicrobial agent used in toothpaste to reduce dental plaque, gingivitis and oral malodor. This community-level assessment evaluated the susceptibility of dental plaque bacteria to triclosan in samples collected over 19 years. A total of 155 dental plaque samples were collected at eleven different times over 19 years from 58 adults using 0.3% triclosan, 2% copolymer, 0.243% sodium fluoride toothpaste and from 97 adults using toothpaste without triclosan. These included samples from 21 subjects who used triclosan toothpaste for at least five years and samples from 20 control subjects. The samples were cultured on media containing 0, 7.5 or 25 μg/ml triclosan. Descriptive statistics and p values were computed and a linear regression model and the runs test were used to examine susceptibility over time. Growth inhibition averaged 99.451% (91.209 - 99.830%) on media containing 7.5 μg/ml triclosan and 99.989% (99.670 - 100%) on media containing 25 μg/ml triclosan. There was no change in microbial susceptibility to triclosan over time discernible by regression analysis or the runs test in plaque samples taken over 19 years including samples from subjects using a triclosan-containing dentifrice for at least five years. This community-level assessment of microbial susceptibility to triclosan among supragingival plaque bacteria is consistent with the long-term safety of a 0.3% triclosan, 2% copolymer, 0.243% sodium fluoride dentifrice.

Cardiovascular Risk Stratification in Patients with Metabolic Syndrome Without Diabetes or Cardiovascular Disease: Usefulness of Metabolic Syndrome Severity Score.

PubMed

Masson, Walter; Epstein, Teo; Huerín, Melina; Lobo, Lorenzo Martín; Molinero, Graciela; Angel, Adriana; Masson, Gerardo; Millán, Diana; De Francesca, Salvador; Vitagliano, Laura; Cafferata, Alberto; Losada, Pablo

2017-09-01

The estimated cardiovascular risk determined by the different risk scores, could be heterogeneous in patients with metabolic syndrome without diabetes or vascular disease. This risk stratification could be improved by detecting subclinical carotid atheromatosis. To estimate the cardiovascular risk measured by different scores in patients with metabolic syndrome and analyze its association with the presence of carotid plaque. Non-diabetic patients with metabolic syndrome (Adult Treatment Panel III definition) without cardiovascular disease were enrolled. The Framingham score, the Reynolds score, the new score proposed by the 2013 ACC/AHA Guidelines and the Metabolic Syndrome Severity Calculator were calculated. Prevalence of carotid plaque was determined by ultrasound examination. A Receiver Operating Characteristic analysis was performed. A total of 238 patients were enrolled. Most patients were stratified as "low risk" by Framingham score (64%) and Reynolds score (70.1%). Using the 2013 ACC/AHA score, 45.3% of the population had a risk ≥7.5%. A significant correlation was found between classic scores but the agreement (concordance) was moderate. The correlation between classical scores and the Metabolic Syndrome Severity Calculator was poor. Overall, the prevalence of carotid plaque was 28.2%. The continuous metabolic syndrome score used in our study showed a good predictive power to detect carotid plaque (area under the curve 0.752). In this population, the calculated cardiovascular risk was heterogenic. The prevalence of carotid plaque was high. The Metabolic Syndrome Severity Calculator showed a good predictive power to detect carotid plaque.

Currently available methodologies for the processing of intravascular ultrasound and optical coherence tomography images.

PubMed

Athanasiou, Lambros; Sakellarios, Antonis I; Bourantas, Christos V; Tsirka, Georgia; Siogkas, Panagiotis; Exarchos, Themis P; Naka, Katerina K; Michalis, Lampros K; Fotiadis, Dimitrios I

2014-07-01

Optical coherence tomography and intravascular ultrasound are the most widely used methodologies in clinical practice as they provide high resolution cross-sectional images that allow comprehensive visualization of the lumen and plaque morphology. Several methods have been developed in recent years to process the output of these imaging modalities, which allow fast, reliable and reproducible detection of the luminal borders and characterization of plaque composition. These methods have proven useful in the study of the atherosclerotic process as they have facilitated analysis of a vast amount of data. This review presents currently available intravascular ultrasound and optical coherence tomography processing methodologies for segmenting and characterizing the plaque area, highlighting their advantages and disadvantages, and discusses the future trends in intravascular imaging.

Antimicrobial efficacy of amine fluoride based tooth gels compared to a toothpaste in a phase 2/step 2 in-vitro test model

PubMed Central

Schiller, Anne; Großjohann, Beatrice; Welk, Alexander; Hübner, Nils-Olaf; Braun, Dagmar; Assadian, Ojan; Kramer, Axel

2012-01-01

Introduction: The aim of the present study was to determine the antimicrobial effect of various gel formulations on plaque formation; different tooth gels were compared to a toothpaste containing comparable antimicrobial ingredients with regard to its microbiocidal activity. The study was conducted under the assumption, that a chief requirement for the prevention of plaque formation is the combination of mechanical removal and antimicrobial activity, and not the sole capability of mechanical plaque removal. Methods: Ledermix® fluoride gel as commercially available with preservative, and without preservative and perfume oils, Elmex® gelée, and Meridol® toothpaste were tested in a standardized in-vitro test modification of the quantitative suspension test EN 1040. Instead of testing in a suspension, the respective product was directly placed on a standardized contaminated sterile stainless steel disk without adding any bio-burden. 50% egg yolk in Aqua dest. was used as a neutralizer. Results: Within 1 min, Elmex® gelée showed a RF >5 log10 against S. pyogenes and S. sanguinis. Against S. mutans, a log10 RF of ≥5 was achieved after 2 min, against C. albicans after 5 min, and against P. aeruginosa after 10 min S. aureus was the most difficult organisms to be reduced. After an application time of 10 min, only a log10 RF of 2.4 was achieved. Ledermix exceeded the antimicrobial efficacy of Elmex® gelée against S. mutans and C. albicans and was already effective against these organisms after 1 min, but did not show the same antimicrobial efficacy as Elmex® gelée against P. aeruginosa. Similar to Elmex® gelée, a required reduction of >5 log10 for antimicrobials under no organic challenge was not achieved against S. aureus. Ledermix® fluoride gel without preservatives and Ledermix® fluoride gel without preservatives and perfume oil did not show the antimicrobial efficacy of the standard Ledermix® fluoride gel formulation, indicating that the observed antimicrobial efficacy is chiefly based on the preservative, and possibly the perfume oil. Compared to the tested gels, Meridol® toothpaste was less effective and reached any antimicrobial effect >5 log10 only against S. sanguinis after 10 min. Conclusion: All unmodified tested gels showed an antimicrobial effect. Because no relevant antimicrobial efficacy against plaque forming bacteria was achieved within 2 min, in practice, an anti-plaque forming effect based on the antimicrobial action of gels cannot be assumed when used in the oral cavity. However, the results of the present study indicate that the antimicrobial efficacy of gels is determined by their formulation and that for the prevention of plaque formation the combination of mechanical removal and antimicrobial activity is not the chief requirement only, but a sustained antimicrobial effect may be of greater importance. PMID:22558041

Analysis of oral microbiota in children with dental caries by PCR-DGGE and barcoded pyrosequencing.

PubMed

Ling, Zongxin; Kong, Jianming; Jia, Peng; Wei, Chaochun; Wang, Yuezhu; Pan, Zhiwen; Huang, Wujing; Li, Lanjuan; Chen, Hui; Xiang, Charlie

2010-10-01

Oral microbiota plays a vital role in maintaining the homeostasis of oral cavity. Dental caries are among the most common oral diseases in children and pathogenic bacteria contribute to the development of the disease. However, the overall structure of bacterial communities in the oral cavity from children with dental caries has not been explored deeply heretofore. We used high-throughput barcoded pyrosequencing and PCR-denaturing gradient gel electrophoresis (DGGE) to examine bacterial diversity of oral microbiota in saliva and supragingival plaques from 60 children aged 3 to 6 years old with and without dental caries from China. The multiplex barcoded pyrosequencing was performed in a single run, with multiple samples tagged uniquely by multiplex identifiers. As PCR-DGGE analysis is a conventional molecular ecological approach, this analysis was also performed on the same samples and the results of both approaches were compared. A total of 186,787 high-quality sequences were obtained for evaluating bacterial diversity and 41,905 unique sequences represented all phylotypes. We found that the oral microbiota in children was far more diverse than previous studies reported, and more than 200 genera belonging to ten phyla were found in the oral cavity. The phylotypes in saliva and supragingival plaques were significantly different and could be divided into two distinct clusters (p < 0.05). The bacterial diversity in oral microbiome analyzed by PCR-DGGE and barcoded pyrosequencing was employed to cross validate the data sets. The genera of Streptococcus, Veillonella, Actinomyces, Granulicatella, Leptotrichia, and Thiomonas in plaques were significantly associated with dental caries (p < 0.05). The results showed that there was no one specific pathogen but rather pathogenic populations in plaque that significantly correlated with dental caries. The enormous diversity of oral microbiota allowed for a better understanding of oral microecosystem, and these pathogenic populations in plaque provide new insights into the etiology of dental caries and suggest new targets for interventions of the disease.

Protection against atherogenesis with the polymer drag-reducing agent Separan AP-30.

PubMed

Faruqui, F I; Otten, M D; Polimeni, P I

1987-03-01

The inhibitory effect of Separan AP-30, an anionic polyacrylamide, on atherosclerotic plaque formation in aortas of rabbits on a high (2%) cholesterol diet was tested over a period extending from 37 to 170 days. Atherogenesis was quantified morphometrically by application of a computer-assisted image analysis of histologic cross sections of the aorta. The area of vessel wall-atheroma interface, fraction of lumen occluded, and other indexes of atherogenesis were measured in each of 26 segments of aorta excised from the animals, half of which were administered injections (intravenous) of Separan three times a week. Regression analysis of the morphometric data indicates that the polyelectrolyte exerts a powerful antiatherogenic effect in all regions of the aorta, inhibiting the formation of plaque mass to less than half in the aortic arch and about one-fifth in the descending aorta as compared with the aortic plaque masses in untreated rabbits. Results are compatible with the suggestion that a novel hemodynamic principle in vivo, polymer drag reduction, might be effectively applied against atherosclerosis.

A Finite Difference Numerical Analysis of Heat Transfer in Atheromatous Plaque for Percutaneous Transluminal Microwave Angioplasty

DTIC Science & Technology

1990-06-01

procedures resulted in varying degrees of vessel wall injuries that occurred at the site of arterial wall dilation. These injuries included intimal ...splitting, subintimal dissection , medial tears, and submedial dissection as shown in Figure 3 (Duber et al., 1986). 5 Tunica Adventitia Tunica Media...of the leg and limbs whereas fatty and fibrofatty plaques are usually deposited in the coronary arteries . Further numerical experiments were

Atherosclerotic lesions in mouse and man: is it the same disease?

PubMed

Bentzon, Jacob Fog; Falk, Erling

2010-10-01

Genetically-engineered mice with hyperlipidemia are the most widely used atherosclerosis models today, but recent advances in transgenesis open the possibility to create new models in alternative species, such as the rat and pig. It seems relevant at this point in time to review some of the strengths and weaknesses of the mouse. The histology of lesion development in mouse and man has more similarities than differences, and comparative genetics show that many mechanisms of murine and human atherogenesis are shared. Unfortunately, the most feared complication of human atherosclerosis, that is, plaque rupture and thrombosis, occur extremely rarely in mice. This is a major problem. Most patients today are not treated before symptoms ensue, and at this late stage of the disease, mechanisms identified during plaque development in the mouse may not be very important. Murine atherosclerosis models are highly valuable for identifying atherogenic mechanisms that can be targeted by preventive medicine. However, models with thrombotic complications and large animal models suitable for interventional procedures and imaging would be more supportive for current clinical practice and are highly wanted.

Mechanical behavior of peripheral stents and stent-vessel interaction: A computational study

NASA Astrophysics Data System (ADS)

Dottori, Serena; Flamini, Vittoria; Vairo, Giuseppe

2016-05-01

In this paper stents employed to treat peripheral artery disease are analyzed through a three-dimensional finite-element approach, based on a large-strain and large-displacement formulation. Aiming to evaluate the influence of some stent design parameters on stent mechanics and on the biomechanical interaction between stent and arterial wall, quasi-static and dynamic numerical analyses are carried out by referring to computational models of commercially and noncommercially available versions of both braided self-expandable stents and balloon-expandable stents. Addressing isolated device models, opening mechanisms and flexibility of both opened and closed stent configurations are numerically experienced. Moreover, stent deployment into a stenotic peripheral artery and possible postdilatation angioplasty (the latter for the self-expandable device only) are simulated by considering different idealized vessel geometries and accounting for the presence of a stenotic plaque. Proposed results highlight important differences in the mechanical response of the two types of stents, as well as a significant influence of the vessel shape on the stress distributions arising upon the artery-plaque system. Finally, computational results are used to assess both the stent mechanical performance and the effectiveness of the stenting treatment, allowing also to identify possible critical conditions affecting the risk of stent fracture, tissue damage, and/or pathological tissue response.

Imaging of lipids in atherosclerotic lesion in aorta from ApoE/LDLR-/- mice by FT-IR spectroscopy and Hierarchical Cluster Analysis.

PubMed

P Wrobel, Tomasz; Mateuszuk, Lukasz; Chlopicki, Stefan; Malek, Kamilla; Baranska, Malgorzata

2011-12-21

Spectroscopy-based approaches can provide an insight into the biochemical composition of a tissue sample. In the present work Fourier transform infrared (FT-IR) spectroscopy was used to develop a reliable methodology to study the content of free fatty acids, triglycerides, cholesteryl esters as well as cholesterol in aorta from mice with atherosclerosis (ApoE/LDLR(-/-) mice). In particular, distribution and concentration of palmitic, oleic and linoleic acid derivatives were analyzed. Spectral analysis of pure compounds allowed for clear discrimination between free fatty acids and other similar moieties based on the carbonyl band position (1699-1710 cm(-1) range). In order to distinguish cholesteryl esters from triglycerides a ratio of carbonyl band to signal at 1010 cm(-1) was used. Imaging of lipids in atherosclerotic aortic lesions in ApoE/LDLR(-/-) mice was followed by Hierarchical Cluster Analysis (HCA). The aorta from C57Bl/6J control mice (fed with chow diet) was used for comparison. The measurements were completed with an FT-IR spectrometer equipped with a 128 × 128 FPA detector. In cross-section of aorta from ApoE/LDLR(-/-) mice a region of atherosclerotic plaque was clearly identified by HCA, which was later divided into 2 sub-regions, one characterized by the higher content of cholesterol, while the other by higher contents of cholesteryl esters. HCA of tissues deposited on normal microscopic glass, hence limited to the 2200-3800 cm(-1) spectral range, also identified a region of atherosclerotic plaque. Importantly, this region correlates with the area stained by standard histological staining for atherosclerotic plaque (Oil Red O). In conclusion, the use of FT-IR and HCA may provide a novel tool for qualitative and quantitative analysis of contents and distribution of lipids in atherosclerotic plaque.

The nature of iron deposits differs between symptomatic and asymptomatic carotid atherosclerotic plaques

DOE PAGES

Kopriva, David; Kisheev, Anastasye; Meena, Deiter; ...

2015-11-25

Iron within atherosclerotic plaque has been implicated as a catalyst of oxidative stress that causes progression of plaque, and plaque rupture. Iron is believed to accumulate within plaque by incorporation of erythrocytes following plaque rupture and hemorrhage. There is only indirect evidence to support this hypothesis. Plaque specimens were obtained from ten symptomatic and fifteen asymptomatic patients undergoing carotid endarterectomy at a single institution. Plaques were sectioned for study using synchrotron radiation induced X-ray fluorescence the study the distribution of zinc, calcium and iron. Histologic staining was carried out with Prussian Blue, and immunohistochemical staining was done to localize macrophagesmore » with CD68. Data were compared against patient clinical variables. Ten symptomatic (15 ± 10 days between index symptoms and surgery) and fifteen asymptomatic carotid plaques were studied. Zinc and calcium co-localized in mineralized areas of symptomatic and asymptomatic plaque. Iron was identified away from zinc and calcium in both symptomatic and asymptomatic plaques. Within the symptomatic plaques, iron was found within the thrombus associated with plaque rupture and hemorrhage. It did not stain with Prussian Blue, but was found in association with CD68 positive macrophages. In symptomatic plaques, the abundance of iron showed an association with the source patient’s LDL cholesterol (R 2 = 0.39, Significance F = 0.05). Iron in asymptomatic plaque was present as hemosiderin/ferritin that stained positive with Prussian Blue, and was observed in association with CD68 positive macrophages. Iron in acutely symptomatic plaques is found within thrombus, in the presence of macrophages. Moreover, the abundance of iron in symptomatic plaques is associated with the source patient’s LDL cholesterol. Within asymptomatic plaques, iron is found in association with macrophages, as hemosiderin/ferritin.« less

The Nature of Iron Deposits Differs between Symptomatic and Asymptomatic Carotid Atherosclerotic Plaques

PubMed Central

Kopriva, David; Kisheev, Anastasye; Meena, Deiter; Pelle, Shaneen; Karnitsky, Max; Lavoie, Andrea; Buttigieg, Josef

2015-01-01

Iron within atherosclerotic plaque has been implicated as a catalyst of oxidative stress that causes progression of plaque, and plaque rupture. Iron is believed to accumulate within plaque by incorporation of erythrocytes following plaque rupture and hemorrhage. There is only indirect evidence to support this hypothesis. Plaque specimens were obtained from ten symptomatic and fifteen asymptomatic patients undergoing carotid endarterectomy at a single institution. Plaques were sectioned for study using synchrotron radiation induced X-ray fluorescence the study the distribution of zinc, calcium and iron. Histologic staining was carried out with Prussian Blue, and immunohistochemical staining was done to localize macrophages with CD68. Data were compared against patient clinical variables. Ten symptomatic (15 ± 10 days between index symptoms and surgery) and fifteen asymptomatic carotid plaques were studied. Zinc and calcium co-localized in mineralized areas of symptomatic and asymptomatic plaque. Iron was identified away from zinc and calcium in both symptomatic and asymptomatic plaques. Within the symptomatic plaques, iron was found within the thrombus associated with plaque rupture and hemorrhage. It did not stain with Prussian Blue, but was found in association with CD68 positive macrophages. In symptomatic plaques, the abundance of iron showed an association with the source patient’s LDL cholesterol (R2 = 0.39, Significance F = 0.05). Iron in asymptomatic plaque was present as hemosiderin/ferritin that stained positive with Prussian Blue, and was observed in association with CD68 positive macrophages. Iron in acutely symptomatic plaques is found within thrombus, in the presence of macrophages. The abundance of iron in symptomatic plaques is associated with the source patient’s LDL cholesterol. Within asymptomatic plaques, iron is found in association with macrophages, as hemosiderin/ferritin. PMID:26606178

The nature of iron deposits differs between symptomatic and asymptomatic carotid atherosclerotic plaques

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

Kopriva, David; Kisheev, Anastasye; Meena, Deiter

Iron within atherosclerotic plaque has been implicated as a catalyst of oxidative stress that causes progression of plaque, and plaque rupture. Iron is believed to accumulate within plaque by incorporation of erythrocytes following plaque rupture and hemorrhage. There is only indirect evidence to support this hypothesis. Plaque specimens were obtained from ten symptomatic and fifteen asymptomatic patients undergoing carotid endarterectomy at a single institution. Plaques were sectioned for study using synchrotron radiation induced X-ray fluorescence the study the distribution of zinc, calcium and iron. Histologic staining was carried out with Prussian Blue, and immunohistochemical staining was done to localize macrophagesmore » with CD68. Data were compared against patient clinical variables. Ten symptomatic (15 ± 10 days between index symptoms and surgery) and fifteen asymptomatic carotid plaques were studied. Zinc and calcium co-localized in mineralized areas of symptomatic and asymptomatic plaque. Iron was identified away from zinc and calcium in both symptomatic and asymptomatic plaques. Within the symptomatic plaques, iron was found within the thrombus associated with plaque rupture and hemorrhage. It did not stain with Prussian Blue, but was found in association with CD68 positive macrophages. In symptomatic plaques, the abundance of iron showed an association with the source patient’s LDL cholesterol (R 2 = 0.39, Significance F = 0.05). Iron in asymptomatic plaque was present as hemosiderin/ferritin that stained positive with Prussian Blue, and was observed in association with CD68 positive macrophages. Iron in acutely symptomatic plaques is found within thrombus, in the presence of macrophages. Moreover, the abundance of iron in symptomatic plaques is associated with the source patient’s LDL cholesterol. Within asymptomatic plaques, iron is found in association with macrophages, as hemosiderin/ferritin.« less

Porphyromonas gingivalis Accelerates Inflammatory Atherosclerosis in the Innominate Artery of ApoE Deficient Mice

PubMed Central

Hayashi, Chie; Viereck, Jason; Hua, Ning; Phinikaridou, Alkystis; Madrigal, Andres G.; Gibson, Frank C.; Hamilton, James A.; Genco, Caroline A.

2011-01-01

Objective Studies in humans support a role for the oral pathogen Porphyromonas gingivalis in the development of inflammatory atherosclerosis. The goal of this study was to determine if P. gingivalis infection accelerates inflammation and atherosclerosis in the innominate artery of mice, an artery which has been reported to exhibit many features of human atherosclerotic disease, including plaque rupture. Methods and Results Apolipoprotein E-deficient (ApoE−/−) mice were orally infected with P. gingivalis, and Magnetic Resonance Imaging (MRI) was used to monitor the progression of atherosclerosis in live mice. P. gingivalis infected mice exhibited a statistically significant increase in atherosclerotic plaque in the innominate artery as compared to uninfected mice. Polarized light microscopy and immunohistochemistry revealed that the innominate arteries of infected mice had increased lipids, macrophages and T cells as compared to uninfected mice. Increases in plaque, total cholesterol esters and cholesterol monohydrate crystals, macrophages, and T cells were prevented by immunization with heat-killed P. gingivalis prior to pathogen exposure. Conclusions These are the first studies to demonstrate progression of inflammatory plaque accumulation in the innominate arteries by in-vivo MRI analysis following pathogen exposure, and to document protection from plaque progression in the innominate artery via immunization. PMID:21251656

Comparative evaluation of terminalia chebula extract mouthwash and chlorhexidine mouthwash on plaque and gingival inflammation - 4-week randomised control trial.

PubMed

Gupta, Devanand; Gupta, Rajendra Kumar; Bhaskar, Dara John; Gupta, Vipul

2015-01-01

The present study was conducted to assess the effectiveness of Terminalia chebula on plaque and gingival inflammation and compare it with the gold standard chlorhexidine (CHX 0.2%) and distilled water as control (placebo). A double-blind randomised control trial was conducted among undergraduate students who volunteered. They were randomly allocated into three study groups: 1) Terminalia chebula mouthwash (n = 30); 2) chlorhexidine (active control) (n = 30); 3) distilled water (placebo) (n = 30). Assessment was carried out according to plaque score and gingival score. Statistical analysis was carried out to compare the effect of both mouthwashes. ANOVA and post-hoc LSD tests were performed using SPSS version 17 with p ≤ 0.05 considered statistically significant. Our result showed that Terminalia chebula mouthrinse is as effective as chlorhexidine in reducing dental plaque and gingival inflammation. The results demonstrated a significant reduction of gingival bleeding and plaque indices in both groups over a period of 15 and 30 days as compared to the placebo. The results of the present study indicate that Terminalia chebula may prove to be an effective mouthwash. Terminalia chebula extract mouthrinse can be used as an alternative to chlorhexidine mouthrinse as it has similar properties without the side-effects of the latter.

Analysis of carotid lumen surface morphology using three-dimensional ultrasound imaging

NASA Astrophysics Data System (ADS)

Chiu, Bernard; Beletsky, Vadim; Spence, J. David; Parraga, Grace; Fenster, Aaron

2009-03-01

Carotid plaque surface irregularity and ulcerations play an important role in the risk of ischemic stroke. Ulcerated or fissured plaque, characterized by irregular surface morphology, exposes thrombogenic materials to the bloodstream, possibly leading to life- or brain-threatening thrombosis and embolization. Therefore, the quantification of plaque surface irregularity is important to identify high-risk plaques that would likely lead to vascular events. Although a number of studies have characterized plaque surface irregularity using subjective classification schemes with two or more categories, only a few have quantified surface irregularity using an objective and continuous quantity, such as Gaussian or mean curvature. In this work, our goal was to use both Gaussian and mean curvatures for identifying ulcers from 3D carotid ultrasound (US) images of human subjects. Before performing experiments using patient data, we verified the numerical accuracy of the surface curvature computation method using discrete spheres and tori with different sampling intervals. We also showed that three ulcers of the vascular phantom with 2 mm, 3 mm and 4 mm diameters were associated with high Gaussian and mean curvatures, and thus, were easily detected. Finally, we demonstrated the application of the proposed method for detecting ulcers on luminal surfaces, which were segmented from the 3D US images acquired for two human subjects.

The antibacterial effect of sage extract (Salvia officinalis) mouthwash against Streptococcus mutans in dental plaque: a randomized clinical trial.

PubMed

Beheshti-Rouy, Maryam; Azarsina, Mohadese; Rezaie-Soufi, Loghman; Alikhani, Mohammad Yousef; Roshanaie, Ghodratollah; Komaki, Samira

2015-06-01

The aim of the study was to evaluate the clinical effects of a mouthwash containing Sage (Salvia officinalis) extracts on Streptococcus mutans (SM) causing dental plaque in school-aged children. A double blind clinical trial study was conducted in a dormitory on 70 girls aged 11-14 years having the same socioeconomic and oral hygiene conditions. These students were randomly divided into 2 groups; the first group (N=35) using Sage mouthwash, and the second group (N=35) using placebo mouthwash without active any ingredients. At the baseline, plaque samples obtained from the buccal surfaces of teeth were sent to laboratory to achieve SM colony count. These tests were reevaluated after 21 days of using the mouthwashes. Statistical data analysis was performed using t-student tests with p<0.05 as the level of significance. Sage mouthwash significantly reduced the colony count (P=0.001). Average number of colonies in test group was 3900 per plaque sample at the baseline, and 300 after mouthwash application. In the control group, pre-test colony count was 4400 that was reduced to 4000; although this reduction wasn't significant. The Sage mouthwash effectively reduced the number of Streptococcus mutans in dental plaque.

Coronary Plaque Morphology and the Anti-Inflammatory Impact of Atorvastatin: A Multicenter 18F-Fluorodeoxyglucose Positron Emission Tomographic/Computed Tomographic Study.

PubMed

Singh, Parmanand; Emami, Hamed; Subramanian, Sharath; Maurovich-Horvat, Pal; Marincheva-Savcheva, Gergana; Medina, Hector M; Abdelbaky, Amr; Alon, Achilles; Shankar, Sudha S; Rudd, James H F; Fayad, Zahi A; Hoffmann, Udo; Tawakol, Ahmed

2016-12-01

Nonobstructive coronary plaques manifesting high-risk morphology (HRM) associate with an increased risk of adverse clinical cardiovascular events. We sought to test the hypothesis that statins have a greater anti-inflammatory effect within coronary plaques containing HRM. In this prospective multicenter study, 55 subjects with or at high risk for atherosclerosis underwent 18 F-fluorodeoxyglucose positron emission tomographic/computed tomographic imaging at baseline and after 12 weeks of treatment with atorvastatin. Coronary arterial inflammation ( 18 F-fluorodeoxyglucose uptake, expressed as target-to-background ratio) was assessed in the left main coronary artery (LMCA). While blinded to the PET findings, contrast-enhanced computed tomographic angiography was performed to characterize the presence of HRM (defined as noncalcified or partially calcified plaques) in the LMCA. Arterial inflammation (target-to-background ratio) was higher in LMCA segments with HRM than those without HRM (mean±SEM: 1.95±0.43 versus 1.67±0.32 for LMCA with versus without HRM, respectively; P=0.04). Moreover, atorvastatin treatment for 12 weeks reduced target-to-background ratio more in LMCA segments with HRM than those without HRM (12 week-baseline Δtarget-to-background ratio [95% confidence interval]: -0.18 [-0.35 to -0.004] versus 0.09 [-0.06 to 0.26]; P=0.02). Furthermore, this relationship between coronary plaque morphology and change in LMCA inflammatory activity remained significant after adjusting for baseline low-density lipoprotein and statin dose (β=-0.27; P=0.038). In this first study to evaluate the impact of statins on coronary inflammation, we observed that the anti-inflammatory impact of statins is substantially greater within coronary plaques that contain HRM features. These findings suggest an additional mechanism by which statins disproportionately benefit individuals with more advanced atherosclerotic disease. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00703261. © 2016 The Authors.

Application of the gingival contour plaque index: six-month plaque and gingivitis study.

PubMed

Scherl, Dale S; Bork, Kim; Coffman, Lori; Lowry, Stephen R; VanCleave, Misty

2009-01-01

The Gingival Contour Plaque Index (GCPI) is a recently introduced and validated method of measuring plaque accumulation in dogs. It focuses on plaque accumulated along the gingival margin. Plaque accumulation in this area leads to gingival inflammation and, potentially, periodontitis. A 6-month plaque and gingivitis study was conducted to demonstrate the clinical research application of the GCPI, and to ensure that documented quantification of plaque-reducing efficacy could be related to a reduction in gingivitis. Advantages of the GCPI method are the ability to quantify plaque accumulation in an awake dog with fewer research personnel and more efficient time usage.

Molecular analysis of 16S rRNA genes identifies potentially periodontal pathogenic bacteria and archaea in the plaque of partially erupted third molars.

PubMed

Mansfield, J M; Campbell, J H; Bhandari, A R; Jesionowski, A M; Vickerman, M M

2012-07-01

Small subunit rRNA sequencing and phylogenetic analysis were used to identify cultivable and uncultivable microorganisms present in the dental plaque of symptomatic and asymptomatic partially erupted third molars to determine the prevalence of putative periodontal pathogens in pericoronal sites. Template DNA prepared from subgingival plaque collected from partially erupted symptomatic and asymptomatic mandibular third molars and healthy incisors was used in polymerase chain reaction with broad-range oligonucleotide primers to amplify 16S rRNA bacterial and archaeal genes. Amplicons were cloned, sequenced, and compared with known nucleotide sequences in online databases to identify the microorganisms present. Two thousand three hundred two clones from the plaque of 12 patients carried bacterial sequences from 63 genera belonging to 11 phyla, including members of the uncultivable TM7, SR1, and Chloroflexi, and difficult-to-cultivate Synergistetes and Spirochaetes. Dialister invisus, Filifactor alocis, Fusobacterium nucleatum, Porphyromonas endodontalis, Prevotella denticola, Tannerella forsythia, and Treponema denticola, which have been associated with periodontal disease, were found in significantly greater abundance in pericoronal compared with incisor sites. Dialister invisus and F nucleatum were found in greater abundance in sites exhibiting clinical symptoms. The archaeal species, Methanobrevibacter oralis, which has been associated with severe periodontitis, was found in 3 symptomatic patients. These findings have provided new insights into the complex microbiota of pericoronitis. Several bacterial and archaeal species implicated in periodontal disease were recovered in greater incidence and abundance from the plaque of partially erupted third molars compared with incisors, supporting the hypothesis that the pericoronal region may provide a favored niche for periodontal pathogens in otherwise healthy mouths. Copyright © 2012 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Arterial wave reflection and subclinical atherosclerosis in rheumatoid arthritis.

PubMed

Gunter, Sule; Robinson, Chanel; Woodiwiss, Angela J; Norton, Gavin R; Hsu, Hon-Chun; Solomon, Ahmed; Tsang, Linda; Millen, Aletta M E; Dessein, Patrick H

2018-01-01

Atherosclerotic cardiovascular disease risk is increased in rheumatoid arthritis (RA). Wave reflection occurs at arterial branching points, which are particularly prone to atherosclerosis. We explored the relationship of wave reflection with atherosclerosis in RA. One hundred and sixty three RA patients (110 white, 31 Asian, 17 black and 5 of mixed ancestry) without cardiovascular disease participated. Arterial stiffness, wave reflection, pressure pulsatility, plaque in the extracranial carotid artery tree and the mean of the left and right common carotid arteries intima-thickness were determined. Associations were identified in multivariable regression models. One SD increase in reflected wave pressure (OR (95% CI) = 2.54 (1.41-4.44), p=0.001), reflection magnitude (OR (95% CI) = 1.84 (1.17-2.89), p=0.008), central pulse pressure (OR (95% CI) = 1.89 (1.12-3.22), p=0.02) and peripheral pulse pressure (OR (95% CI) = 2.09 (1.23-3.57), p=0.007) were associated with plaque. The association of wave reflection with plaque was independent of arterial stiffness and pressure pulsatility, and was present in both hypertensive and normotensive RA patients. In receiver operator characteristic curve analysis, the optimal cutoff value for reflected wave pressure in predicting plaque presence was 25 mmHg with a sensitivity, specificity, positive predictive value and negative predictive value of 45.2%, 89.3%, 78.6% and 66.2%, respectively; a reflected wave pressure of >25 mmHg was associated with plaque in univariate and adjusted analysis (p<0.0001 for both). Arterial function was not independently related to carotid intima-media thickness. Consideration and therapeutic targeting of wave reflection may improve cardiovascular disease prevention in RA.

Detection of attenuated plaque in stable angina with 64-multidetector computed tomography: a comparison with intravascular ultrasound.

PubMed

Jinzaki, Masahiro; Okabe, Teruo; Endo, Ayaka; Kawamura, Akio; Koga, Seiko; Yamada, Minoru; Fukuda, Keiichi; Kuribayashi, Sachio

2012-01-01

To clarify multidetector computed tomography (MDCT) findings of attenuated plaque detected by intravascular ultrasound (IVUS). One hundred and fifty-four patients with stable angina underwent MDCT before IVUS. The attenuated plaque was identified in the targeted artery with IVUS, and the same artery was analyzed with MDCT for the presence of a high density area (HDA) >130 Hounsfield units (HU), and a low density area (LDA) <30 HU. A HDA in attenuated plaque was compared with that in calcified plaque. Ten attenuated plaques and 15 calcified plaques were identified in 9 of 154 patients (males=9, 66.2 ± 9.5 years). Eight of the 10 attenuated plaques and all 15 calcified plaques were accompanied with a HDA on MDCT. The HDA ranged from 174 to 667 HU (mean 389.0 ± 148.3 HU) in the 8 attenuated plaques, and from 545 to 1,205 HU (mean 920.9 ± 215.9 HU) in 15 calcified plaques. There was a significant difference in CT density of the HDA between the attenuated and calcified plaque (P<0.001). All attenuated plaques contained LDA <30 HU in the portions without HDA. MDCT has the ability to demonstrate attenuated plaque as the combination of HDA (approximately 400 HU on average) and LDA <30 HU. The HDA can be differentiated from calcified plaque by its lower CT density value.

Influence of reminder therapy for controlling bacterial plaque in patients undergoing orthodontic treatment: A systematic review and meta-analysis.

PubMed

Lima, Igor Felipe Pereira; de Andrade Vieira, Walbert; de Macedo Bernardino, Ítalo; Costa, Pedro Augusto; Lima, Anderson Paulo Barbosa; Pithon, Matheus Melo; Paranhos, Luiz Renato

2018-04-17

To assess the scientific evidence regarding the influence of reminder therapy on plaque index, gingival index, and white spots in patients subjected to orthodontic treatment. Randomized clinical trials were searched in the electronic databases LILACS, PubMed, SciELO, Scopus, Web of Science, Embase, LIVIVO, and Cochrane Library. The databases OpenThesis and OpenGrey were used to capture the "gray literature," preventing selection and publication biases. The risk of bias was assessed by the Joanna Briggs Institute Critical Appraisal Checklist for Randomized Controlled Trials tool. The software Review Manager was used for the meta-analysis. The heterogeneity among studies was assessed through the I 2 statistic. A summary of the overall strength of evidence available was assessed using the Grades of Recommendations Assessment, Development, and Evaluation tool. A total of 332 records were found, from which only 7 articles met the inclusion criteria and were subjected to analysis. Reminder therapy showed improved scores for the plaque index (standardized mean difference = -1.22; 95% confidence interval = -2.03 to -0.42; P = .003) and the gingival index (standardized mean difference = 1.49; 95% confidence interval = -2.61 to 0.37; P = .009). Moreover, there was lower occurrence of white spots (relative risk = 0.53; 95% confidence interval = 0.38 to 0.74; P < .001) when reminder therapy was implemented. According to the existing high-quality evidence, reminder therapy is a valuable strategy and may contribute to the reduction of plaque and gingival indices as well as to the lower occurrence of white spots in patients subjected to orthodontic treatment.

Effect of slice thickness on brain magnetic resonance image texture analysis

PubMed Central

2010-01-01

Background The accuracy of texture analysis in clinical evaluation of magnetic resonance images depends considerably on imaging arrangements and various image quality parameters. In this paper, we study the effect of slice thickness on brain tissue texture analysis using a statistical approach and classification of T1-weighted images of clinically confirmed multiple sclerosis patients. Methods We averaged the intensities of three consecutive 1-mm slices to simulate 3-mm slices. Two hundred sixty-four texture parameters were calculated for both the original and the averaged slices. Wilcoxon's signed ranks test was used to find differences between the regions of interest representing white matter and multiple sclerosis plaques. Linear and nonlinear discriminant analyses were applied with several separate training and test sets to determine the actual classification accuracy. Results Only moderate differences in distributions of the texture parameter value for 1-mm and simulated 3-mm-thick slices were found. Our study also showed that white matter areas are well separable from multiple sclerosis plaques even if the slice thickness differs between training and test sets. Conclusions Three-millimeter-thick magnetic resonance image slices acquired with a 1.5 T clinical magnetic resonance scanner seem to be sufficient for texture analysis of multiple sclerosis plaques and white matter tissue. PMID:20955567

Characterization of human arterial tissue affected by atherosclerosis using multimodal nonlinear optical microscopy

NASA Astrophysics Data System (ADS)

Baria, Enrico; Cicchi, Riccardo; Rotellini, Matteo; Nesi, Gabriella; Massi, Daniela; Pavone, Francesco S.

2016-03-01

Atherosclerosis is a widespread cardiovascular disease caused by the deposition of lipids (such as cholesterol and triglycerides) on the inner arterial wall. The rupture of an atherosclerotic plaque, resulting in a thrombus, is one of the leading causes of death in the Western World. Preventive assessment of plaque vulnerability is therefore extremely important and can be performed by studying collagen organization and lipid composition in atherosclerotic arterial tissues. Routinely used diagnostic methods, such as histopathological examination, are limited to morphological analysis of the examined tissues, whereas an exhaustive characterization requires immune-histochemical examination and a morpho-functional approach. Instead, a label-free and non-invasive alternative is provided by nonlinear microscopy. In this study, we combined SHG and FLIM microscopy in order to characterize collagen organization and lipids in human carotid ex vivo tissues affected by atherosclerosis. SHG and TPF images, acquired from different regions within atherosclerotic plaques, were processed through image pattern analysis methods (FFT, GLCM). The resulting information on collagen and cholesterol distribution and anisotropy, combined with collagen and lipids fluorescence lifetime measured from FLIM images, allowed characterization of carotid samples and discrimination of different tissue regions. The presented method can be applied for automated classification of atherosclerotic lesions and plaque vulnerability. Moreover, it lays the foundation for a potential in vivo diagnostic tool to be used in clinical setting.

Automated tissue characterization of in vivo atherosclerotic plaques by intravascular optical coherence tomography images

PubMed Central

Ughi, Giovanni Jacopo; Adriaenssens, Tom; Sinnaeve, Peter; Desmet, Walter; D’hooge, Jan

2013-01-01

Intravascular optical coherence tomography (IVOCT) is rapidly becoming the method of choice for the in vivo investigation of coronary artery disease. While IVOCT visualizes atherosclerotic plaques with a resolution <20µm, image analysis in terms of tissue composition is currently performed by a time-consuming manual procedure based on the qualitative interpretation of image features. We illustrate an algorithm for the automated and systematic characterization of IVOCT atherosclerotic tissue. The proposed method consists in a supervised classification of image pixels according to textural features combined with the estimated value of the optical attenuation coefficient. IVOCT images of 64 plaques, from 49 in vivo IVOCT data sets, constituted the algorithm’s training and testing data sets. Validation was obtained by comparing automated analysis results to the manual assessment of atherosclerotic plaques. An overall pixel-wise accuracy of 81.5% with a classification feasibility of 76.5% and per-class accuracy of 89.5%, 72.1% and 79.5% for fibrotic, calcified and lipid-rich tissue respectively, was found. Moreover, measured optical properties were in agreement with previous results reported in literature. As such, an algorithm for automated tissue characterization was developed and validated using in vivo human data, suggesting that it can be applied to clinical IVOCT data. This might be an important step towards the integration of IVOCT in cardiovascular research and routine clinical practice. PMID:23847728

A Novel Murine Candidiasis Model with Severe Colonization in the Stomach Induced by N-acetylglucosamine-treatment and Its Scoring System Based on Local Characteristic Stomach Symptoms.

PubMed

Ishijima, Sanae A; Abe, Shigeru

2015-01-01

We developed a novel murine candidiasis model of the gastrointestinal tract using N-acetylglucosamine ( GlcNAc ) as a tool to aggravate symptoms. Forty-eight hours after intragastrically inoculating Candida albicans cells to immunosuppressed and GlcNAc-treated mice, vigorously accumulating patchy whitish plaques were observed on their inner stomach surface. Candida cells colonizing the plaques consisted of both yeast and mycelia, and were directly stained with Calcofluor White M2R. Aggravation of the candidiasis symptoms was dependent on GlcNAc concentration in drinking water, wherein administration of 50 mM GlcNAc not only severely worsened stomach symptoms, but also significantly increased Candida cell number in the stomach and small intestine. The aggravation effect of GlcNAc was enhanced by addition of sedative chemical chlorpromazine chloride after inoculation. In order to semi-quantitatively assess colonization by Candida in the stomach, we devised a new symptom scoring system that represents the extent of the patchy whitish plaques on the mucosal epithelium of the stomach. Histochemical analysis of Candida-infected tissues revealed not only a large amount of thick Candida mycelia invading mucosal epithelial stomach tissues but also infiltrating inflammatory cells. These results suggest that this murine gastrointestinal candidiasis model could serve as a useful tool for evaluating the protective activity of antifungal agents, probiotics, or functional foods against gastrointestinal candidiasis. Furthermore, from another point of view, this novel murine model could also be used to analyze the pathological mechanisms behind the translocation of C. albicans across intestinal barriers, which results in systemic Candida dissemination and infection.

Anti-atherosclerotic effects of pravastatin in brachiocephalic artery in comparison with en face aorta and aortic roots in ApoE/LDLR-/- mice.

PubMed

Kostogrys, Renata B; Franczyk-Zarow, Magdalena; Gasior-Glogowska, Marlena; Kus, Edyta; Jasztal, Agnieszka; Wrobel, Tomasz P; Baranska, Malgorzata; Czyzynska-Cichon, Izabela; Drahun, Anna; Manterys, Angelika; Chlopicki, Stefan

2017-02-01

Cholesterol-dependent and independent mechanisms were proposed to explain anti-atherosclerotic action of statins in humans. However, their effects in murine models of atherosclerosis have not been consistently demonstrated. Here, we studied the effects of pravastatin on atherosclerosis in ApoE/LDLR -/- mice fed a control and atherogenic diet. ApoE/LDLR -/- mice were fed a control (CHOW) or an atherogenic (Low Carbohydrate High Protein, LCHP) diet. Two doses of pravastatin (40mg/kg and 100mg/kg) were used. The anti-atherosclerotic effects of pravastatin in en face aorta, cross-sections of aortic roots and brachiocephalic artery (BCA) were analysed. The lipid profile was determined. Fourier Transform Infrared Spectroscopy followed by Fuzzy C-Means (FCM) clustering was used for the quantitative assessment of plaque composition. Treatment with pravastatin (100mg/kg) decreased total and LDL cholesterol only in the LCHP group, but displayed a pronounced anti-atherosclerotic effect in BCA and abdominal aorta. The anti-atherosclerotic effect of pravastatin (100mg/kg) in BCA was associated with significant alterations of the chemical plaque composition, including a fall in cholesterol and cholesterol esters contents independently on total cholesterol and LDL concentration in plasma. Pravastatin at high (100mg/kg), but not low dose displayed a pronounced anti-atherosclerotic effect in ApoE/LDLR -/- mice fed a CHOW or LCHP diet that was remarkable in BCA, visible in en face aorta, whereas it was not observed in aortic roots, suggesting that previous inconsistencies might have been due to the various sites of atherosclerotic plaque analysis. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

Characterisation of Atherogenic Effects of Low Carbohydrate, High Protein Diet (LCHP) in ApoE/LDLR-/- Mice.

PubMed

Kostogrys, R B; Johann, C; Czyżyńska, I; Franczyk-Żarów, M; Drahun, A; Maślak, E; Jasztal, A; Gajda, M; Mateuszuk, Ł; Wrobel, T P; Baranska, M; Wybrańska, I; Jezkova, K; Nachtigal, P; Chlopicki, S

2015-08-01

Low Carbohydrate High Protein diet represents a popular strategy to achieve weight loss. The aim of this study was to characterize effects of low carbohydrate, high protein diet (LCHP) on atherosclerotic plaque development in brachiocephalic artery (BCA) in apoE/LDLR-/- mice and to elucidate mechanisms of proatherogenic effects of LCHP diet. Atherosclerosis plaques in brachiocephalic artery (BCA) as well as in aortic roots, lipoprotein profile, inflammation biomarkers, expression of SREBP-1 in the liver as well as mortality were analyzed in Control diet (AIN-93G) or LCHP (Low Carbohydrate High Protein) diet fed mice. Area of atherosclerotic plaques in aortic roots or BCA from LCHP diet fed mice was substantially increased as compared to mice fed control diet and was characterized by increased lipids and cholesterol contents (ORO staining, FT-IR analysis), increased macrophage infiltration (MOMA-2) and activity of MMPs (zymography). Pro-atherogenic phenotype of LCHP fed apoE/LDLR-/- mice was associated with increased plasma total cholesterol concentration, and in LDL and VLDL fractions, increased TG contents in VLDL, and a modest increase in plasma urea. LCHP diet increased SCD-1 index, activated SREBP-1 transcription factor in the liver and triggered acute phase response as evidence by an increased plasma concentration of haptoglobin, CRP or AGP. Finally, in long-term experiment survival of apoE/LDLR-/- mice fed LCHP diet was substantially reduced as compared to their counterparts fed control diet suggesting overall detrimental effects of LCHP diet on health. The pro-atherogenic effect of LCHP diet in apoE/LDLR-/- mice is associated with profound increase in LDL and VLDL cholesterol, VLDL triglicerides, liver SREBP-1 upregulation, and systemic inflammation.

Neuroinflammation, hyperphosphorylated tau, diffuse amyloid plaques, and down-regulation of the cellular prion protein in air pollution exposed children and young adults.

PubMed

Calderón-Garcidueñas, Lilian; Kavanaugh, Michael; Block, Michelle; D'Angiulli, Amedeo; Delgado-Chávez, Ricardo; Torres-Jardón, Ricardo; González-Maciel, Angelica; Reynoso-Robles, Rafael; Osnaya, Norma; Villarreal-Calderon, Rodolfo; Guo, Ruixin; Hua, Zhaowei; Zhu, Hongtu; Perry, George; Diaz, Philippe

2012-01-01

Air pollution exposures have been linked to neuroinflammation and neuropathology. Autopsy samples of the frontal cortex from control (n = 8) and pollution-exposed (n = 35) children and young adults were analyzed by RT-PCR (n = 43) and microarray analysis (n = 12) for gene expression changes in oxidative stress, DNA damage signaling, NFκB signaling, inflammation, and neurodegeneration pathways. The effect of apolipoprotein E (APOE) genotype on the presence of protein aggregates associated with Alzheimer's disease (AD) pathology was also explored. Exposed urbanites displayed differential (>2-fold) regulation of 134 genes. Forty percent exhibited tau hyperphosphorylation with pre-tangle material and 51% had amyloid-β (Aβ) diffuse plaques compared with 0% in controls. APOE4 carriers had greater hyperphosphorylated tau and diffuse Aβ plaques versus E3 carriers (Q = 7.82, p = 0.005). Upregulated gene network clusters included IL1, NFκB, TNF, IFN, and TLRs. A 15-fold frontal down-regulation of the prion-related protein (PrP(C)) was seen in highly exposed subjects. The down-regulation of the PrP(C) is critical given its important roles for neuroprotection, neurodegeneration, and mood disorder states. Elevation of indices of neuroinflammation and oxidative stress, down-regulation of the PrP(C) and AD-associated pathology are present in young megacity residents. The inducible regulation of gene expression suggests they are evolving different mechanisms in an attempt to cope with the constant state of inflammation and oxidative stress related to their environmental exposures. Together, these data support a role for air pollution in CNS damage and its impact upon the developing brain and the potential etiology of AD and mood disorders.

High-resolution magnetic resonance imaging of carotid atherosclerotic plaques - a correlation study with histopathology.

PubMed

Xia, Zhangyong; Yang, Hua; Yuan, Xiaochun; Wang, Jiyue; Zhang, Shigang; Zhang, Liyong; Qu, Yang; Chen, Jun; Jiao, Liqun; Wang, Le-Xin; Du, Yifeng

2017-07-01

This study aimed to utilize high-resolution magnetic resonance imaging (MRI) to investigate the characteristics of stable and vulnerable carotid arteriosclerotic plaques, with correlations to histopathological findings. High-resolution MRI was performed in 817 patients, using three-dimensional magnetic resonance angiography. Plaque composition was evaluated by measuring the areas occupied by calcification, a lipid-rich necrotic core, intra-plaque haemorrhage, and fibrous cap rupture. Plaque morphology was analysed by measuring vessel wall area, thickness, and luminal area at the bifurcation of the common carotid artery. Plaque tissues were sampled during carotid endarterectomy and examined using haematoxylin-eosin, Oil Red O, Masson trichrome staining, and immunohistochemical staining for CD68. Patients were divided into stable plaque group (n = 462) and vulnerable plaque group (n = 355), based on intraoperative observations and postoperative histopathological findings. Compared to the stable plaque group, the vulnerable plaque group exhibited increased vessel wall areas and thickness, and decreased mean luminal areas (P < 0.001). The vulnerable plaque group also had a lower collagen content, a higher lipid content, and higher CD68 expression in plaque tissues on histological examinations (P < 0.01). Incidences of lipid-rich necrotic core (38.1 % vs. 34.3 %), intra-plaque haemorrhage (26.9 % vs. 22.8 %), plaque calcification (45.2 % vs. 40.9 %), and fibrous cap rupture (36.0 % vs 39.8 %) in the plaques were concordant with MRI observations and histopathological findings (p > 0.05). Stable and vulnerable carotid plaques had different morphologies and compositions. High-resolution MRI can assess such differences qualitatively and quantitatively in vivo and provide guidance for risk stratification and management.

[Pathophysiological role of tissue renin-angiotensin-aldosterone system (RAAS) in human atherosclerosis].

PubMed

Fukui, Kensuke; Yamada, Hiroyuki; Matsubara, Hiroaki

2012-09-01

Renin-angiotensin-aldosterone system (RAAS) has been demonstrated to play an important role in the pathogenesis of atherosclerosis development both in animal experiments and in clinical studies. Numerous clinical studies have shown that blockade of RAAS exerts beneficial effects to restore the impaired endothelial function and to reduce the mortality and morbidity of cardiovascular diseases beyond their blood pressure lowering effect. However, the underlying mechanisms of stabilizing vulnerable plaque and inhibiting plaque rupture associated with acute coronary syndrome have not yet been fully elucidated. Here, we summarized the characteristics of tissue RAAS expressions in human atherosclerotic lesions and assessed their therapeutic relevance in the prevention of atherosclerotic cardiovascular diseases.

The inter-observer agreement in the assessment of carotid plaque neovascularization by contrast-enhanced ultrasonography: The impact of plaque thickness.

PubMed

Chen, Jian; Zhang, Yan-Ming; Song, Ze-Zhou; Fu, Yan-Fei; Geng, Yu

2018-04-10

The interobserver agreement in the assessment of the grade of carotid plaque neovascularization by contrast-enhanced ultrasonography is poorly established. We examined 140 carotid plaques in 66 patients (all patients had bilateral plaques, and 8 patients had 2 plaques on one side). We performed conventional and contrast-enhanced ultrasonography to analyze the presence of carotid plaque neovascularization, which was graded by two independent observers whose interobserver agreement (κ) was evaluated according to the thickness of carotid plaque. For all carotid plaques, the mean κ was 0.689 (95% confidence interval 0.604-0.774). It was 0.689 (0.569-0.808), 0.637 (0.487-0.787), and 0.740 (0.585-0.896), respectively for carotid plaques with maximal thickness <2 mm, from 2 mm to 3 mm, and >3 mm. The interobserver agreement for assessing carotid plaque neovascularization by using contrast-enhanced ultrasonography is substantial and acceptable for research purposes, regardless of the maximal thickness of the plaque. © 2018 Wiley Periodicals, Inc.

Virulent variants emerging in mice infected with the apathogenic prototype strain of the parvovirus minute virus of mice exhibit a capsid with low avidity for a primary receptor.

PubMed

Rubio, Mari-Paz; López-Bueno, Alberto; Almendral, José M

2005-09-01

The mechanisms involved in the emergence of virulent mammalian viruses were investigated in the adult immunodeficient SCID mouse infected by the attenuated prototype strain of the parvovirus Minute Virus of Mice (MVMp). Cloned MVMp intravenously inoculated in mice consistently evolved during weeks of subclinical infection to variants showing altered plaque phenotypes. All the isolated large-plaque variants spread systemically from the oronasal cavity and replicated in major organs (brain, kidney, liver), in sharp contrast to the absolute inability of the MVMp and small-plaque variants to productively invade SCID organs by this natural route of infection. The virulent variants retained the MVMp capacity to infect mouse fibroblasts, consistent with the lack of genetic changes across the 220-to-335 amino acid sequence of VP2, a capsid domain containing main determinants of MVM tropism. However, the capsid of the virulent variants shared a lower affinity than the wild type for a primary receptor used in the cytotoxic infection. The capsid gene of a virulent variant engineered in the MVMp background endowed the recombinant virus with a large-plaque phenotype, lower affinity for the receptor, and productive invasiveness by the oronasal route in SCID mice, eventually leading to 100% mortality. In the analysis of virulence in mice, both MVMp and the recombinant virus similarly gained the bloodstream 1 to 2 days postoronasal inoculation and remained infectious when adsorbed to blood cells in vitro. However, the wild-type MVMp was cleared from circulation a few days afterwards, in contrast to the viremia of the recombinant virus, which was sustained for life. Significantly, attachment to an abundant receptor of primary mouse kidney epithelial cells by both viruses could be quantitatively competed by wild-type MVMp capsids, indicating that virulence is not due to an extended receptor usage in target tissues. We conclude that the selection of capsid-receptor interactions of low affinity, which favors systemic infection, is a major evolutionary process in the adaptation of parvoviruses to new hosts and in the cause of disease.

Virulent Variants Emerging in Mice Infected with the Apathogenic Prototype Strain of the Parvovirus Minute Virus of Mice Exhibit a Capsid with Low Avidity for a Primary Receptor

PubMed Central

Rubio, Mari-Paz; López-Bueno, Alberto; Almendral, José M.

2005-01-01

The mechanisms involved in the emergence of virulent mammalian viruses were investigated in the adult immunodeficient SCID mouse infected by the attenuated prototype strain of the parvovirus Minute Virus of Mice (MVMp). Cloned MVMp intravenously inoculated in mice consistently evolved during weeks of subclinical infection to variants showing altered plaque phenotypes. All the isolated large-plaque variants spread systemically from the oronasal cavity and replicated in major organs (brain, kidney, liver), in sharp contrast to the absolute inability of the MVMp and small-plaque variants to productively invade SCID organs by this natural route of infection. The virulent variants retained the MVMp capacity to infect mouse fibroblasts, consistent with the lack of genetic changes across the 220-to-335 amino acid sequence of VP2, a capsid domain containing main determinants of MVM tropism. However, the capsid of the virulent variants shared a lower affinity than the wild type for a primary receptor used in the cytotoxic infection. The capsid gene of a virulent variant engineered in the MVMp background endowed the recombinant virus with a large-plaque phenotype, lower affinity for the receptor, and productive invasiveness by the oronasal route in SCID mice, eventually leading to 100% mortality. In the analysis of virulence in mice, both MVMp and the recombinant virus similarly gained the bloodstream 1 to 2 days postoronasal inoculation and remained infectious when adsorbed to blood cells in vitro. However, the wild-type MVMp was cleared from circulation a few days afterwards, in contrast to the viremia of the recombinant virus, which was sustained for life. Significantly, attachment to an abundant receptor of primary mouse kidney epithelial cells by both viruses could be quantitatively competed by wild-type MVMp capsids, indicating that virulence is not due to an extended receptor usage in target tissues. We conclude that the selection of capsid-receptor interactions of low affinity, which favors systemic infection, is a major evolutionary process in the adaptation of parvoviruses to new hosts and in the cause of disease. PMID:16103180

Effect of medicinal plants on the crystallization of cholesterol

NASA Astrophysics Data System (ADS)

Saraswathi, N. T.; Gnanam, F. D.

1997-08-01

One of the least desirable calcifications in the human body is the mineral deposition in atherosclerosis plaques. These plaques principally consist of lipids such as cholesterol, cholesteryl esters, phospholipids and triglycerides. Chemical analysis of advanced plaques have shown the presence of considerable amounts of free cholesterol identified as cholesterol monohydrate crystals. Cholesterol has been crystallized in vitro. The extracts of some of the Indian medicinal plants detailed below were used as additives to study their effect on the crystallization behaviour of cholesterol. It has been found that many of the herbs have inhibitory effect on the crystallization such as nucleation, crystal size and habit modification. The inhibitory effect of the plants are graded as Commiphora mughul > Aegle marmeleos > Cynoden dactylon > Musa paradisiaca > Polygala javana > Alphinia officinarum > Solanum trilobatum > Enicostemma lyssopifolium.

The usefulness of optical analyses for detecting vulnerable plaques using rabbit models

NASA Astrophysics Data System (ADS)

Nakai, Kanji; Ishihara, Miya; Kawauchi, Satoko; Shiomi, Masashi; Kikuchi, Makoto; Kaji, Tatsumi

2011-03-01

Purpose: Carotid artery stenting (CAS) has become a widely used option for treatment of carotid stenosis. Although technical improvements have led to a decrease in complications related to CAS, distal embolism continues to be a problem. The purpose of this research was to investigate the usefulness of optical methods (Time-Resolved Laser- Induced Fluorescence Spectroscopy [TR-LIFS] and reflection spectroscopy [RS] as diagnostic tools for assessment of vulnerable atherosclerotic lesions, using rabbit models of vulnerable plaque. Materials & Methods: Male Japanese white rabbits were divided into a high cholesterol diet group and a normal diet group. In addition, we used a Watanabe heritable hyperlipidemic (WHHL) rabbit, because we confirmed the reliability of our animal model for this study. Experiment 1: TR-LIFS. Fluorescence was induced using the third harmonic wave of a Q switch Nd:YAG laser. The TR-LIFS was performed using a photonic multi-channel analyzer with ICCD (wavelength range, 200 - 860 nm). Experiment 2: RS. Refection spectra in the wavelength range of 900 to 1700 nm were acquired using a spectrometer. Results: In the TR-LIFS, the wavelength at the peak was longer by plaque formation. The TR-LIFS method revealed a difference in peak levels between a normal aorta and a lipid-rich aorta. The RS method showed increased absorption from 1450 to 1500 nm for lipid-rich plaques. We observed absorption around 1200 nm due to lipid only in the WHHL group. Conclusion: These methods using optical analysis might be useful for diagnosis of vulnerable plaques. Keywords: Carotid artery stenting, vulnerable plaque, Time-Resolved Laser-Induced Fluorescence

Does the presence of the Helicobacter pylori in the dental plaque associate with its gastric infection? A meta-analysis and systematic review

PubMed Central

Navabi, Nader; Aramon, Moein; Mirzazadeh, Ali

2011-01-01

Background: There is a great deal of studies on the relationship between the existence of Helicobacter pylori (H. pylori) in oral cavity (dental plaque) and in stomach of patients, with conflicting results worldwide. The purpose of this study was to systematically review the existing litreature to assess if the dental plaque could be a source of gastric H. pylori infection and to explore the source of heterogeneity around it. Methods: We searched all the papers published since 2000 on international (Medline, ISI, Embase) databases using standard keywords. Two researchers evaluated the articles with standard critical appraisal form independently and those articles with the quality acquired greater than 70% were included in the study. The combined results were calculated with weighted average and the source of hetrogeneity was tested by meta-regression (random) model. Results: Finally, 23 studies were included (1861 patients). The prevalence of co-infection of gastric and dental plaque H. pylori was 49.7% (95% CI 16–83.4%) and the percent of agreement between the dental plaque H. pylori status and the gastric H. pylori was estimated as 82%. Only one study has reported that dental treatment has a preventive effect on the recurrence of gastric H. pylori infection. Conclusion: Co-infection of gastric H. pylori and dental plaque is reported by half of the studies. However, there is not enough evidence for the efficacy of dental treatment on prevention of recurrent gastric H. pylori infection. PMID:22135688

Plaque Tissue Morphology-Based Stroke Risk Stratification Using Carotid Ultrasound: A Polling-Based PCA Learning Paradigm.

PubMed

Saba, Luca; Jain, Pankaj K; Suri, Harman S; Ikeda, Nobutaka; Araki, Tadashi; Singh, Bikesh K; Nicolaides, Andrew; Shafique, Shoaib; Gupta, Ajay; Laird, John R; Suri, Jasjit S

2017-06-01

Severe atherosclerosis disease in carotid arteries causes stenosis which in turn leads to stroke. Machine learning systems have been previously developed for plaque wall risk assessment using morphology-based characterization. The fundamental assumption in such systems is the extraction of the grayscale features of the plaque region. Even though these systems have the ability to perform risk stratification, they lack the ability to achieve higher performance due their inability to select and retain dominant features. This paper introduces a polling-based principal component analysis (PCA) strategy embedded in the machine learning framework to select and retain dominant features, resulting in superior performance. This leads to more stability and reliability. The automated system uses offline image data along with the ground truth labels to generate the parameters, which are then used to transform the online grayscale features to predict the risk of stroke. A set of sixteen grayscale plaque features is computed. Utilizing the cross-validation protocol (K = 10), and the PCA cutoff of 0.995, the machine learning system is able to achieve an accuracy of 98.55 and 98.83%corresponding to the carotidfar wall and near wall plaques, respectively. The corresponding reliability of the system was 94.56 and 95.63%, respectively. The automated system was validated against the manual risk assessment system and the precision of merit for same cross-validation settings and PCA cutoffs are 98.28 and 93.92%for the far and the near wall, respectively.PCA-embedded morphology-based plaque characterization shows a powerful strategy for risk assessment and can be adapted in clinical settings.

Augmenting Amyloid PET Interpretations With Quantitative Information Improves Consistency of Early Amyloid Detection.

PubMed

Harn, Nicholas R; Hunt, Suzanne L; Hill, Jacqueline; Vidoni, Eric; Perry, Mark; Burns, Jeffrey M

2017-08-01

Establishing reliable methods for interpreting elevated cerebral amyloid-β plaque on PET scans is increasingly important for radiologists, as availability of PET imaging in clinical practice increases. We examined a 3-step method to detect plaque in cognitively normal older adults, focusing on the additive value of quantitative information during the PET scan interpretation process. Fifty-five F-florbetapir PET scans were evaluated by 3 experienced raters. Scans were first visually interpreted as having "elevated" or "nonelevated" plaque burden ("Visual Read"). Images were then processed using a standardized quantitative analysis software (MIMneuro) to generate whole brain and region of interest SUV ratios. This "Quantitative Read" was considered elevated if at least 2 of 6 regions of interest had an SUV ratio of more than 1.1. The final interpretation combined both visual and quantitative data together ("VisQ Read"). Cohen kappa values were assessed as a measure of interpretation agreement. Plaque was elevated in 25.5% to 29.1% of the 165 total Visual Reads. Interrater agreement was strong (kappa = 0.73-0.82) and consistent with reported values. Quantitative Reads were elevated in 45.5% of participants. Final VisQ Reads changed from initial Visual Reads in 16 interpretations (9.7%), with most changing from "nonelevated" Visual Reads to "elevated." These changed interpretations demonstrated lower plaque quantification than those initially read as "elevated" that remained unchanged. Interrater variability improved for VisQ Reads with the addition of quantitative information (kappa = 0.88-0.96). Inclusion of quantitative information increases consistency of PET scan interpretations for early detection of cerebral amyloid-β plaque accumulation.

Comparative analysis of cell proliferation ratio in plaque and erosive oral lichen planus: An immunohistochemical study.

PubMed

Redder, C Pramod; Pandit, Siddharth; Desai, Dinkar; Kandagal, V Suresh; Ingaleshwar, Pramod S; Shetty, Sharan J; Vibhute, Nupura

2014-05-01

Proliferating cell nuclear antigen (PCNA) is a nuclear protein synthesized in the late G1 and S-phase of the cell cycle. Detection of this protein represents a useful marker of the proliferation status of lesions. This study has been carried out to evaluate the cell proliferation rate in oral lichen planus (OLP) and comparison between plaque and erosive lichen planus, which indicates the potential for malignant transformation. This study was comprised of 64 cases of histologically proven lichen planus, out of which 32 cases of plaque and erosive each was taken. Two sections were taken from each, one for H and E staining to verify histological diagnosis according to Eisenberg criteria, other sections were stained according to super sensitive polymer horse radish peroxidise method for identifying immunohistochemical expression of PCNA. Data were statistically analyzed by Tukey high-range statistical domain test. Statistically significant P value was considered <0.05. In two types of lichen planus, erosive type (66.86%) showed higher expression of PCNA followed by plaque (17.07%). Overall, P value was <0.001, which was statistically significant. It indicates that proliferation activity is more in erosive lichen planus followed by plaque type, which ultimately results in increased rate of malignant transformation. PCNA is a good nuclear protein marker to evaluate the proliferation status of OLP. Out of the two types of lichen planus, erosive type possesses more proliferative ratio and chances of malignant change is more in this type. It emphasizes the importance of long-term follow-up with erosive type when compared with plaque type.