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Sample records for neuritic plaque density

  1. Genetic susceptibility for Alzheimer disease neuritic plaque pathology.

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    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.

  2. Visualization of neuritic plaques in Alzheimer’s disease by polarization-sensitive optical coherence microscopy

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    Baumann, Bernhard; Woehrer, Adelheid; Ricken, Gerda; Augustin, Marco; Mitter, Christian; Pircher, Michael; Kovacs, Gabor G.; Hitzenberger, Christoph K.

    2017-03-01

    One major hallmark of Alzheimer’s disease (AD) and cerebral amyloid angiopathy (CAA) is the deposition of extracellular senile plaques and vessel wall deposits composed of amyloid-beta (Aβ). In AD, degeneration of neurons is preceded by the formation of Aβ plaques, which show different morphological forms. Most of them are birefringent owing to the parallel arrangement of amyloid fibrils. Here, we present polarization sensitive optical coherence microscopy (PS-OCM) for imaging mature neuriticplaques based on their birefringent properties. Formalin-fixed, post-mortem brain samples of advanced stage AD patients were investigated. In several cortical brain regions, neuriticplaques were successfully visualized in tomographic and three-dimensional (3D) images. Cortical grey matter appeared polarization preserving, whereas neuritic plaques caused increased phase retardation. Consistent with the results from PS-OCM imaging, the 3D structure of senile Aβ plaques was computationally modelled for different illumination settings and plaque sizes. Furthermore, the birefringent properties of cortical and meningeal vessel walls in CAA were investigated in selected samples. Significantly increased birefringence was found in smaller vessels. Overall, these results provide evidence that PS-OCM is able to assess amyloidosis based on intrinsic birefringent properties.

  3. Existing plaques and neuritic abnormalities in APP:PS1 mice are not affected by administration of the gamma-secretase inhibitor LY-411575

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    Golde Todd E

    2009-05-01

    Full Text Available Abstract The γ-secretase complex is a major therapeutic target for the prevention and treatment of Alzheimer's disease. Previous studies have shown that treatment of young APP mice with specific inhibitors of γ-secretase prevented formation of new plaques. It has not yet been shown directly whether existing plaques would be affected by γ-secretase inhibitor treatment. Similarly, alterations in neuronal morphology in the immediate vicinity of plaques represent a plaque-specific neurotoxic effect. Reversal of these alterations is an important endpoint of successful therapy whether or not a treatment affects plaque size. In the present study we used longitudinal imaging in vivo with multiphoton microscopy to study the effects of the orally active γ-secretase inhibitor LY-411575 in 10–11 month old APP:PS1 mice with established amyloid pathology and neuritic abnormalities. Neurons expressed YFP allowing fluorescent detection of morphology whereas plaques were labelled with methoxy-XO4. The same identified neurites and plaques were followed in weekly imaging sessions in living mice treated daily (5 mg/kg for 3 weeks with the compound. Although LY-411575 reduced Aβ levels in plasma and brain, it did not have an effect on the size of existing plaques. There was also no effect on the abnormal neuritic curvature near plaques, or the dystrophies in very close proximity to senile plaques. Our results suggest that therapeutics aimed at inhibition of Aβ generation are less effective for reversal of existing plaques than for prevention of new plaque formation and have no effect on the plaque-mediated neuritic abnormalities, at least under these conditions where Aβ production is suppressed but not completely blocked. Therefore, a combination therapy of Aβ suppression with agents that increase clearance of amyloid and/or prevent neurotoxicity might be needed for a more effective treatment in patients with pre-existing pathology.

  4. Comparison of neurite density measured by MRI and histology after TBI.

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    Shiyang Wang

    Full Text Available Functional recovery after brain injury in animals is improved by marrow stromal cells (MSC which stimulate neurite reorganization. However, MRI measurement of neurite density changes after injury has not been performed. In this study, we investigate the feasibility of MRI measurement of neurite density in an animal model of traumatic brain injury (TBI with and without MSC treatment.Fifteen male Wistar rats, were treated with saline (n = 6 or MSCs (n = 9 and were sacrificed at 6 weeks after controlled cortical impact (CCI. Healthy non-CCI rats (n = 5, were also employed. Ex-vivo MRI scans were performed two days after the rats were sacrificed. Multiple-shell hybrid diffusion imaging encoding scheme and spherical harmonic expansion of a two-compartment water diffusion displacement model were used to extract neurite related parameters. Bielshowski and Luxol Fast blue was used for staining axons and myelin, respectively. Modified Morris water maze and neurological severity score (mNSS test were performed for functional evaluation. The treatment effects, the correlations between neurite densities measured by MRI and histology, and the correlations between MRI and functional variables were calculated by repeated measures analysis of variance, the regression correlation analysis tests, and spearman correlation coefficients.Neurite densities exhibited a significant correlation (R(2>0.80, p<1E-20 between MRI and immuno-histochemistry measurements with 95% lower bound of the intra-correlation coefficient (ICC as 0.86. The conventional fractional anisotropy (FA correlated moderately with histological neurite density (R(2 = 0.59, P<1E-5 with 95% lower bound of ICC as 0.76. MRI data revealed increased neurite reorganization with MSC treatment compared with saline treatment, confirmed by histological data from the same animals. mNSS were significantly correlated with MRI neurite density in the hippocampus region.The present studies

  5. Performance of [18F]flutemetamol amyloid imaging against the neuritic plaque component of CERAD and the current (2012) NIA-AA recommendations for the neuropathologic diagnosis of Alzheimer's disease.

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    Salloway, Stephen; Gamez, Jose E; Singh, Upinder; Sadowsky, Carl H; Villena, Teresa; Sabbagh, Marwan N; Beach, Thomas G; Duara, Ranjan; Fleisher, Adam S; Frey, Kirk A; Walker, Zuzana; Hunjan, Arvinder; Escovar, Yavir M; Agronin, Marc E; Ross, Joel; Bozoki, Andrea; Akinola, Mary; Shi, Jiong; Vandenberghe, Rik; Ikonomovic, Milos D; Sherwin, Paul F; Farrar, Gill; Smith, Adrian P L; Buckley, Christopher J; Thal, Dietmar Rudolf; Zanette, Michelle; Curtis, Craig

    2017-01-01

    Performance of the amyloid tracer [ 18 F]flutemetamol was evaluated against three pathology standard of truth (SoT) measures including neuritic plaques (CERAD "original" and "modified" and the amyloid component of the 2012 NIA-AA guidelines). After [ 18 F]flutemetamol imaging, 106 end-of-life patients who died underwent postmortem brain examination for amyloid plaque load. Blinded positron emission tomography scan interpretations by five independent electronically trained readers were compared with pathology measures. By SoT, sensitivity and specificity of majority image interpretations were, respectively, 91.9% and 87.5% with "original CERAD," 90.8% and 90.0% with "modified CERAD," and 85.7% and 100% with the 2012 NIA-AA criteria. The high accuracy of either CERAD criteria suggests that [ 18 F]flutemetamol predominantly reflects neuritic amyloid plaque density. However, the use of CERAD criteria as the SoT can result in some false-positive results because of the presence of diffuse plaques, which are accounted for when the positron emission tomography read is compared with the 2012 NIA-AA criteria.

  6. White matter microstructure pathology in classic galactosemia revealed by neurite orientation dispersion and density imaging.

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    Timmers, Inge; Zhang, Hui; Bastiani, Matteo; Jansma, Bernadette M; Roebroeck, Alard; Rubio-Gozalbo, M Estela

    2015-03-01

    White matter abnormalities have been observed in patients with classic galactosemia, an inborn error of galactose metabolism. However, magnetic resonance imaging (MRI) data collected in the past were generally qualitative in nature. Our objective was to investigate white matter microstructure pathology and examine correlations with outcome and behaviour in this disease, by using multi-shell diffusion weighted imaging. In addition to standard diffusion tensor imaging (DTI), neurite orientation dispersion and density imaging (NODDI) was used to estimate density and orientation dispersion of neurites in a group of eight patients (aged 16-21 years) and eight healthy controls (aged 15-20 years). Extensive white matter abnormalities were found: neurite density index (NDI) was lower in the patient group in bilateral anterior areas, and orientation dispersion index (ODI) was increased mainly in the left hemisphere. These specific regional profiles are in agreement with the cognitive profile observed in galactosemia, showing higher order cognitive impairments, and language and motor impairments, respectively. Less favourable white matter properties correlated positively with age and age at onset of diet, and negatively with behavioural outcome (e.g. visual working memory). To conclude, this study provides evidence of white matter pathology regarding density and dispersion of neurites in these patients. The results are discussed in light of suggested pathophysiological mechanisms.

  7. Deficits in Neurite Density Underlie White Matter Structure Abnormalities in First-Episode Psychosis.

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    Rae, Charlotte L; Davies, Geoff; Garfinkel, Sarah N; Gabel, Matt C; Dowell, Nicholas G; Cercignani, Mara; Seth, Anil K; Greenwood, Kathryn E; Medford, Nick; Critchley, Hugo D

    2017-11-15

    Structural abnormalities across multiple white matter tracts are recognized in people with early psychosis, consistent with dysconnectivity as a neuropathological account of symptom expression. We applied advanced neuroimaging techniques to characterize microstructural white matter abnormalities for a deeper understanding of the developmental etiology of psychosis. Thirty-five first-episode psychosis patients, and 19 healthy controls, participated in a quantitative neuroimaging study using neurite orientation dispersion and density imaging, a multishell diffusion-weighted magnetic resonance imaging technique that distinguishes white matter fiber arrangement and geometry from changes in neurite density. Fractional anisotropy (FA) and mean diffusivity images were also derived. Tract-based spatial statistics compared white matter structure between patients and control subjects and tested associations with age, symptom severity, and medication. Patients with first-episode psychosis had lower regional FA in multiple commissural, corticospinal, and association tracts. These abnormalities predominantly colocalized with regions of reduced neurite density, rather than aberrant fiber bundle arrangement (orientation dispersion index). There was no direct relationship with active symptoms. FA decreased and orientation dispersion index increased with age in patients, but not control subjects, suggesting accelerated effects of white matter geometry change. Deficits in neurite density appear fundamental to abnormalities in white matter integrity in early psychosis. In the first application of neurite orientation dispersion and density imaging in psychosis, we found that processes compromising axonal fiber number, density, and myelination, rather than processes leading to spatial disruption of fiber organization, are implicated in the etiology of psychosis. This accords with a neurodevelopmental origin of aberrant brain-wide structural connectivity predisposing individuals to

  8. Early long-term administration of the CSF1R inhibitor PLX3397 ablates microglia and reduces accumulation of intraneuronal amyloid, neuritic plaque deposition and pre-fibrillar oligomers in 5XFAD mouse model of Alzheimer's disease.

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    Sosna, Justyna; Philipp, Stephan; Albay, Ricardo; Reyes-Ruiz, Jorge Mauricio; Baglietto-Vargas, David; LaFerla, Frank M; Glabe, Charles G

    2018-03-01

    Besides the two main classical features of amyloid beta aggregation and tau-containing neurofibrillary tangle deposition, neuroinflammation plays an important yet unclear role in the pathophysiology of Alzheimer's disease (AD). Microglia are believed to be key mediators of neuroinflammation during AD and responsible for the regulation of brain homeostasis by balancing neurotoxicity and neuroprotective events. We have previously reported evidence that neuritic plaques are derived from dead neurons that have accumulated intraneuronal amyloid and further recruit Iba1-positive cells, which play a role in either neuronal demise or neuritic plaque maturation or both. To study the impact of microglia on neuritic plaque development, we treated two-month-old 5XFAD mice with a selective colony stimulation factor 1 receptor (CSF1R) inhibitor, PLX3397, for a period of 3 months, resulting in a significant ablation of microglia. Directly after this treatment, we analyzed the amount of intraneuronal amyloid and neuritic plaques and performed behavioral studies including Y-maze, fear conditioning and elevated plus maze. We found that early long-term PLX3397 administration results in a dramatic reduction of both intraneuronal amyloid as well as neuritic plaque deposition. PLX3397 treated young 5XFAD mice also displayed a significant decrease of soluble fibrillar amyloid oligomers in brain lysates, a depletion of soluble pre-fibrillar oligomers in plasma and an improvement in cognitive function measured by fear conditioning tests. Our findings demonstrate that CSF1R signaling, either directly on neurons or mediated by microglia, is crucial for the accumulation of intraneuronal amyloid and formation of neuritic plaques, suggesting that these two events are serially linked in a causal pathway leading to neurodegeneration and neuritic plaque formation. CSF1R inhibitors represent potential preventative or therapeutic approach that target the very earliest stages of the formation of

  9. Age-dependent differences in brain tissue microstructure assessed with neurite orientation dispersion and density imaging.

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    Merluzzi, Andrew P; Dean, Douglas C; Adluru, Nagesh; Suryawanshi, Gaurav S; Okonkwo, Ozioma C; Oh, Jennifer M; Hermann, Bruce P; Sager, Mark A; Asthana, Sanjay; Zhang, Hui; Johnson, Sterling C; Alexander, Andrew L; Bendlin, Barbara B

    2016-07-01

    Human aging is accompanied by progressive changes in executive function and memory, but the biological mechanisms underlying these phenomena are not fully understood. Using neurite orientation dispersion and density imaging, we sought to examine the relationship between age, cellular microstructure, and neuropsychological scores in 116 late middle-aged, cognitively asymptomatic participants. Results revealed widespread increases in the volume fraction of isotropic diffusion and localized decreases in neurite density in frontal white matter regions with increasing age. In addition, several of these microstructural alterations were associated with poorer performance on tests of memory and executive function. These results suggest that neurite orientation dispersion and density imaging is capable of measuring age-related brain changes and the neural correlates of poorer performance on tests of cognitive functioning, largely in accordance with published histological findings and brain-imaging studies of people of this age range. Ultimately, this study sheds light on the processes underlying normal brain development in adulthood, knowledge that is critical for differentiating healthy aging from changes associated with dementia. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. White Matter Changes of Neurite Density and Fiber Orientation Dispersion during Human Brain Maturation.

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    Yi Shin Chang

    Full Text Available Diffusion tensor imaging (DTI studies of human brain development have consistently shown widespread, but nonlinear increases in white matter anisotropy through childhood, adolescence, and into adulthood. However, despite its sensitivity to changes in tissue microstructure, DTI lacks the specificity to disentangle distinct microstructural features of white and gray matter. Neurite orientation dispersion and density imaging (NODDI is a recently proposed multi-compartment biophysical model of brain microstructure that can estimate non-collinear properties of white matter, such as neurite orientation dispersion index (ODI and neurite density index (NDI. In this study, we apply NODDI to 66 healthy controls aged 7-63 years to investigate changes of ODI and NDI with brain maturation, with comparison to standard DTI metrics. Using both region-of-interest and voxel-wise analyses, we find that NDI exhibits striking increases over the studied age range following a logarithmic growth pattern, while ODI rises following an exponential growth pattern. This novel finding is consistent with well-established age-related changes of FA over the lifespan that show growth during childhood and adolescence, plateau during early adulthood, and accelerating decay after the fourth decade of life. Our results suggest that the rise of FA during the first two decades of life is dominated by increasing NDI, while the fall in FA after the fourth decade is driven by the exponential rise of ODI that overcomes the slower increases of NDI. Using partial least squares regression, we further demonstrate that NODDI better predicts chronological age than DTI. Finally, we show excellent test-retest reliability of NODDI metrics, with coefficients of variation below 5% in all measured regions of interest. Our results support the conclusion that NODDI reveals biologically specific characteristics of brain development that are more closely linked to the microstructural features of white

  11. Restriction spectrum imaging reveals decreased neurite density in patients with temporal lobe epilepsy.

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    Loi, Richard Q; Leyden, Kelly M; Balachandra, Akshara; Uttarwar, Vedang; Hagler, Donald J; Paul, Brianna M; Dale, Anders M; White, Nathan S; McDonald, Carrie R

    2016-11-01

    Diffusion tensor imaging (DTI) has become a popular tool for delineating the location and extent of white matter injury in temporal lobe epilepsy (TLE). However, DTI yields nonspecific measures that are confounded by changes occurring within both the intracellular and extracellular environments. This study investigated whether an advanced diffusion method, restriction spectrum imaging (RSI) could provide a more robust measure of white matter injury in TLE relative to DTI due to RSI's ability to separate intraaxonal diffusion (i.e., neurite density; ND) from diffusion associated with extraaxonal factors (e.g., inflammation; crossing fibers). RSI and DTI scans were obtained on 21 patients with TLE and 11 age-matched controls. RSI-derived maps of ND, isotropic-hindered (IH) and isotropic-free (IF) water, and crossing fibers (CFs) were compared to DTI-derived fractional anisotropy (FA) maps. Voxelwise and tract-based analyses were performed comparing patients with TLE to controls on each diffusion metric. Reductions in FA were seen primarily in frontotemporal white matter in TLE, and they were most pronounced proximal to the seizure focus. Reductions in ND corresponded to those seen in the FA maps; however, ND reductions were greater in magnitude, more lateralized to the epileptogenic hemisphere, and showed a broader pattern. Increases in IF/IH and effects from CFs also contributed to reduced FA in the ipsilateral parahippocampal cingulum and fornix, with decreases in IH extending into extratemporal regions. Reduced ND of the uncinate fasciculus was associated with longer disease duration, whereas FA was not associated with any clinical variables. RSI may provide a more specific measure of white matter pathology in TLE, distinguishing regions primarily affected by axonal/myelin loss from those where CFs and increases in extracellular water also play a role. By providing a more specific measure of axonal/myelin loss, RSI-derived ND may better reflect overall white

  12. Application of neurite orientation dispersion and density imaging (NODDI) to a tau pathology model of Alzheimer's disease.

    LENUS (Irish Health Repository)

    Colgan, N

    2015-10-23

    Increased hyperphosphorylated tau and the formation of intracellular neurofibrillary tangles are associated with the loss of neurons and cognitive decline in Alzheimer\\'s disease, and related neurodegenerative conditions. We applied two diffusion models, diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI), to in vivo diffusion magnetic resonance images (dMRI) of a mouse model of human tauopathy (rTg4510) at 8.5months of age. In grey matter regions with the highest degree of tau burden, microstructural indices provided by both NODDI and DTI discriminated the rTg4510 (TG) animals from wild type (WT) controls; however only the neurite density index (NDI) (the volume fraction that comprises axons or dendrites) from the NODDI model correlated with the histological measurements of the levels of hyperphosphorylated tau protein. Reductions in diffusion directionality were observed when implementing both models in the white matter region of the corpus callosum, with lower fractional anisotropy (DTI) and higher orientation dispersion (NODDI) observed in the TG animals. In comparison to DTI, histological measures of tau pathology were more closely correlated with NODDI parameters in this region. This in vivo dMRI study demonstrates that NODDI identifies potential tissue sources contributing to DTI indices and NODDI may provide greater specificity to pathology in Alzheimer\\'s disease.

  13. Familial influence on plaque formation in the beagle brain.

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    Russell, M J; White, R; Patel, E; Markesbery, W R; Watson, C R; Geddes, J W

    1992-12-01

    Aged canines exhibit central neuropathological changes strikingly similar to those seen in patients with Alzheimer's disease. In this study, brain tissue from pure bred beagles raised in a controlled environment were examined for Alzheimer-like pathology. The mean age of the animals was 15.6 years. The incidence of plaques among these 29 dogs was 65.5%. Of the 19 samples that demonstrated Alzheimer-like pathology, 18 were characterized as diffuse and one as neuritic. Plaque density was found to be independent of age. Plaque numbers were highest in the perirhinal cortex and the adjacent temporal cortex. Familial influence on plaque development is supported by congruence within 15 of the 16 litters examined (p < 0.001). In this environmentally controlled group the diffuse plaques were rarely converted to the dense neuritic plaques found in Alzheimer's disease.

  14. Subependymal plaques in scrapie-affected hamster brains--why are they so different from compact kuru plaques?

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    Sikorska, Beata; Liberski, Paweł P; Brown, Paul

    2008-01-01

    We report here routine thin-section and immunogold electron microscopic studies on diffuse plaques in scrapie-affected hamster brains. These plaques were not discernible by routine HE staining. Ultrastructurally, plaques were recognized as areas of low electron density containing haphazardly-oriented fibrils, but not as stellate compact structures typical of mouse scrapie models; hence we labelled them "loose plaques". Following immunohistochemistry at the electron microscopy level, fibrils within plaques were heavily decorated with PrP-conjugated gold particles. Loose plaques were located beneath the basal border of the ependymal cells and around blood vessels in the adjacent subependymal neuropil. When dystrophic neurites containing electron-dense inclusion bodies, some of them autophagic vacuoles [59], were seen within the plaque perimeter, they always remained PrP-negative. Some microglial cells were observed in close contact with PrP-positive plaques, and secondary lysosomes within these cells were heavily decorated with gold particles.

  15. MiR-130a regulates neurite outgrowth and dendritic spine density by targeting MeCP2

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    Yunjia Zhang

    2016-06-01

    Full Text Available ABSTRACT MicroRNAs (miRNAs are critical for both development and function of the central nervous system. Significant evidence suggests that abnormal expression of miRNAs is associated with neurodevelopmental disorders. MeCP2 protein is an epigenetic regulator repressing or activating gene transcription by binding to methylated DNA. Both loss-of-function and gain-of-function mutations in the MECP2 gene lead to neurodevelopmental disorders such as Rett syndrome, autism and MECP2 duplication syndrome. In this study, we demonstrate that miR-130a inhibits neurite outgrowth and reduces dendritic spine density as well as dendritic complexity. Bioinformatics analyses, cell cultures and biochemical experiments indicate that miR-130a targets MECP2 and down-regulates MeCP2 protein expression. Furthermore, expression of the wild-type MeCP2, but not a loss-of-function mutant, rescues the miR-130a-induced phenotype. Our study uncovers the MECP2 gene as a previous unknown target for miR-130a, supporting that miR-130a may play a role in neurodevelopment by regulating MeCP2. Together with data from other groups, our work suggests that a feedback regulatory mechanism involving both miR-130a and MeCP2 may serve to ensure their appropriate expression and function in neural development.

  16. A statin-loaded reconstituted high-density lipoprotein nanoparticle inhibits atherosclerotic plaque inflammation

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    Duivenvoorden, Raphaël; Tang, Jun; Cormode, David P.; Mieszawska, Aneta J.; Izquierdo-Garcia, David; Ozcan, Canturk; Otten, Maarten J.; Zaidi, Neeha; Lobatto, Mark E.; van Rijs, Sarian M.; Priem, Bram; Kuan, Emma L.; Martel, Catherine; Hewing, Bernd; Sager, Hendrik; Nahrendorf, Matthias; Randolph, Gwendalyn J.; Stroes, Erik S. G.; Fuster, Valentin; Fisher, Edward A.; Fayad, Zahi A.; Mulder, Willem J. M.

    2014-01-01

    Inflammation is a key feature of atherosclerosis and a target for therapy. Statins have potent anti-inflammatory properties but these cannot be fully exploited with oral statin therapy due to low systemic bioavailability. Here we present an injectable reconstituted high-density lipoprotein (rHDL) nanoparticle carrier vehicle that delivers statins to atherosclerotic plaques. We demonstrate the anti-inflammatory effect of statin-rHDL in vitro and show that this effect is mediated through the inhibition of the mevalonate pathway. We also apply statin-rHDL nanoparticles in vivo in an apolipoprotein E-knockout mouse model of atherosclerosis and show that they accumulate in atherosclerotic lesions in which they directly affect plaque macrophages. Finally, we demonstrate that a 3-month low-dose statin-rHDL treatment regimen inhibits plaque inflammation progression, while a 1-week high-dose regimen markedly decreases inflammation in advanced atherosclerotic plaques. Statin-rHDL represents a novel potent atherosclerosis nanotherapy that directly affects plaque inflammation.

  17. Molecular Imaging of Low-density Lipoprotein in Human Coronary Plaques by Color Fluorescent Angioscopy and Microscopy

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    Uchida, Yasumi; Maezawa, Yuko; Uchida, Yasuto; Hiruta, Nobuyuki; Shimoyama, Ei

    2012-01-01

    Objectives Low-density lipoprotein (LDL) is an important risk factor for coronary artery disease. However, its localization in human coronary plaques is not well understood. The present study was performed to visualize LDL in human coronary artery wall. Methods (1) The fluorescence characteristic of LDL was investigated by color fluorescent microscopy (CFM) with excitation at 470-nm and emission at 515-nm using Nile blue dye (NB) as a biomarker. (2) Native LDL in 40 normal segments, 42 white plaques and 35 yellow plaques (20 with necrotic core) of human coronary arteries was investigated by color fluorescent angioscopy (CFA) and CFM. Results (1) NB elicited a brown, golden and red fluorescence characteristic of LDL, apolipoprotein B-100, and lysophosphatidylcholine/triglyceride, respectively. (2) The % incidence of LDL in normal segments, white, and yellow plaques was 25, 38 and 14 by CFA and 42, 42 and 14 by CFM scan of their luminal surface, respectively, indicating lower incidence (p<0.05) of LDL in yellow plaques than white plaques, and no significant differences in detection sensitivity between CFA and CFM. By CFM transected surface scan, LDL deposited more frequently and more diffusely in white plaques and yellow plaques without necrotic core (NC) than normal segments and yellow plaques with NC. LDL was localized to fibrous cap in yellow plaques with NC. Co-deposition of LDL with other lipid components was observed frequently in white plaques and yellow plaques without NC. Conclusions (1) Taken into consideration of the well-known process of coronary plaque growth, the results of the present study suggest that LDL begins to deposit before plaque formation; increasingly deposits with plaque growth, often co-depositing with other lipid components; and disappears after necrotic core formation. (2) CFA is feasible for visualization of LDL in human coronary artery wall. PMID:23209809

  18. Localization of oxidized low-density lipoprotein and its relation to plaque morphology in human coronary artery.

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    Yasumi Uchida

    Full Text Available OBJECTIVES: Oxidized low-density lipoprotein (oxLDL plays a key role in the formation of atherosclerotic plaques. However, its localization in human coronary arterial wall is not well understood. The present study was performed to visualize deposition sites and patterns of native oxLDL and their relation to plaque morphology in human coronary artery. METHODS: Evans blue dye (EB elicits a violet fluorescence by excitation at 345-nm and emission at 420-nm, and a reddish-brown fluorescence by excitation at 470-nm and emission at 515-nm characteristic of oxLDL only. Therefore, native oxLDL in excised human coronary artery were investigated by color fluorescent microscopy (CFM using EB as a biomarker. RESULTS: (1 By luminal surface scan with CFM, the % incidence of oxLDL in 38 normal segments, 41 white plaques and 32 yellow plaques that were classified by conventional angioscopy, was respectively 26, 44 and 94, indicating significantly (p<0.05 higher incidence in the latter than the former two groups. Distribution pattern was classified as patchy, diffuse and web-like. Web-like pattern was observed only in yellow plaques with necrotic core. (2 By transected surface scan, oxLDL deposited within superficial layer in normal segments and diffusely within both superficial and deep layers in white and yellow plaques. In yellow plaques with necrotic core, oxLDL deposited not only in the marginal zone of the necrotic core but also in the fibrous cap. CONCLUSION: Taken into consideration of the well-known process of coronary plaque growth, the results suggest that oxLDL begins to deposit in human coronary artery wall before plaque formation and increasingly deposits with plaque growth, exhibiting different deposition sites and patterns depending on morphological changes.

  19. Relationship between enhanced intensity of contrast enhanced ultrasound and microvessel density of aortic atherosclerostic plaque in rabbit model.

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    Xiangdong You

    Full Text Available The aim of this study was to evaluate the relationship between enhanced intensity of contrast enhanced ultrasound and microvessel density of aortic atherosclerotic plaque in rabbit model. The abdominal aortas of thirty-six male New Zealand rabbits were damaged by balloon expansion and the animals were then fed a high fat diet for 12 weeks. Twenty-seven plaques on the near aortic wall were detected using conventional ultrasound examination. The maximum thickness of each plaque was recorded. CEUS was performed on these 27 plaques and the time-intensity curves (TICs were analyzed offline. Using the quantitative ACQ software, features such as the arrival time (AT, time to peak (TTP, baseline intensity (BI, peak intensity (PI and enhanced intensity (EI (EI = PI-BI were assessed. Inter- and intra-observer agreement of EI were assessed using the Bland-Altman test. After CEUS examination, the rabbits were sacrificed for pathological examination and CD34 monoclonal antibody immunohistochemical detection. Microvessel density (MVD was counted under the microscope. The relationship between indexes of CEUS and the level of MVD was analyzed. There was a good positive linear correlation between EI and MVD (γ = 0. 854, P<0. 001, the intraclass correlations for inter- and intra-observer agreement for EI were 0.73 and 0.82 respectively, suggesting that EI may be act as a useful index for plaque risk stratification in animal models.

  20. Microvessel Density But Not Neoangiogenesis Is Associated with (18)F-FDG Uptake in Human Atherosclerotic Carotid Plaques

    DEFF Research Database (Denmark)

    Pedersen, Sune Folke; Græbe, Martin; Hag, Anne Mette Fisker

    2011-01-01

    endothelial growth factor (VEGF) and integrin aV and integrin ß3 subunits, genes essential during neoangiogenesis. We also evaluated the gene expression of CD34, a measure of microvessel density (MVD), as well as CD68, MMP-9, and cathepsin K, genes of major importance in plaque vulnerability. Gene expression...... analysis was compared with 18FDG-PET. Results: VEGF and integrin aVß3 gene expression did not correlate with 18FDG uptake, whereas CD34 gene expression exhibited an inverse correlation with 18FDG uptake. Additionally, we established that markers of vulnerability were correlated with 18FDG uptake...

  1. Salidroside Decreases Atherosclerotic Plaque Formation in Low-Density Lipoprotein Receptor-Deficient Mice

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    Bu-Chun Zhang

    2012-01-01

    Full Text Available Salidroside is isolated from Rhodiola rosea and is one of the main active components in Rhodiola species. The present study was designed to evaluate the effects of Salidroside on atherosclerotic plaque formation in high-fat diet-(HFD- fed female LDL receptor knockout (LDLr-/- mice. LDLr-/- mice fed an atherogenic HFD for 12 weeks were divided into two groups. One group was administered Salidroside (50 mg/kg/oral gavage daily for 8 weeks, while the control group was administered saline. Salidroside treatment reduced serum lipids levels and the plaque area through the arch to the abdominal aorta. Furthermore, Salidroside improved macrophage content and enhanced collagen and smooth muscle cells contents in the aortic sinus. These changes were associated with reduced MCP-1, VCAM-1, and VCAM-1 protein expression in atherosclerotic aortas. All these results suggest that Salidroside decreases atherosclerotic plaques formation via effects on lipid lowering and anti-inflammation in HFD-fed LDLr−/− mice.

  2. Presence of Striatal Amyloid Plaques in Parkinson's Disease Dementia Predicts Concomitant Alzheimer's Disease: Usefulness for Amyloid Imaging.

    Science.gov (United States)

    Dugger, Brittany N; Serrano, Geidy E; Sue, Lucia I; Walker, Douglas G; Adler, Charles H; Shill, Holly A; Sabbagh, Marwan N; Caviness, John N; Hidalgo, Jose; Saxon-Labelle, Megan; Chiarolanza, Glenn; Mariner, Monica; Henry-Watson, Jonette; Beach, Thomas G

    2012-01-01

    Dementia is a frequent complication of Parkinson's disease (PD). About half of PD dementia (PDD) is hypothesized to be due to progression of the underlying Lewy body pathology into limbic regions and the cerebral cortex while the other half is thought to be due to coexistent Alzheimer's disease. Clinically, however, these are indistinguishable. The spread of amyloid plaques to the striatum has been reported to be a sensitive and specific indicator of dementia due to Alzheimer's disease (AD). The purpose of the present study was to determine if the presence of striatal plaques might also be a useful indicator of the presence of diagnostic levels of AD pathology within PD subjects. We analyzed neuropathologically-confirmed cases of PD without dementia (PDND, N = 31), PDD without AD (PDD, N = 31) and PD with dementia meeting clinicopathological criteria for AD (PDAD, N =40). The minimum diagnostic criterion for AD was defined as including a clinical history of dementia, moderate or frequent CERAD cortical neuritic plaque density and Braak neurofibrillary stage III-VI. Striatal amyloid plaque densities were determined using Campbell-Switzer and Thioflavine S stains. Striatal plaque densities were significantly higher in PDAD compared to PDD (p<0.001). The presence of striatal plaques was approximately 80% sensitive and 80% specific for predicting AD. In comparison, the presence of cerebral cortex plaques alone was highly sensitive (100%) but had poor specificity (48% to 55%). The results suggest that striatal amyloid imaging may be clinically useful for making the distinction between PDD and PDAD.

  3. Vulnerable Plaque

    Science.gov (United States)

    ... Center > Vulnerable Plaque Menu Topics Topics FAQs Vulnerable Plaque Article Info En español Swelling (inflammation) is your ... aging, including coronary artery disease . What is vulnerable plaque? For many years, doctors have thought that the ...

  4. APOE4 carriers and non-carriers with the clinical diagnosis of Alzheimer’s dementia and minimal amyloid plaques

    Science.gov (United States)

    Monsell, Sarah E.; Kukull, Walter A.; Roher, Alex E.; Maarouf, Chera L.; Serrano, Geidy; Beach, Thomas G.; Caselli, Richard J.; Montine, Thomas J.; Reiman, Eric M.

    2016-01-01

    Importance Amyloid-β (Aβ) plaques are a cardinal neuropathological feature of Alzheimer’s disease (AD), yet over a third of apolipoprotein E ε4 (APOE4) non-carriers with the clinical diagnosis of mild-to-moderate Alzheimer’s dementia may not meet positron emission tomography (PET) criteria for significant cerebral amyloidosis. Objective This study sought to clarify the percentage of APOE4 carriers and non-carriers with the primary clinical diagnosis of mild-to-moderate Alzheimer’s dementia near the end of life and minimal Aβ plaques at autopsy—and the extent to which these cases are associated with appreciable neurofibrillary degeneration or a primary neuropathologic diagnosis other than AD. Design Participants in this study were obtained from the National Alzheimer’s Coordinating Center’s Uniform Data Set (UDS). Setting The UDS comprises longitudinal clinical assessments performed at the Alzheimer's Disease Centers funded by the National Institute on Aging. Neuropathology data is available for the subset of expired participants. Participants Exactly 100 APOE4 non-carriers and 100 carriers had the primary clinical diagnosis of mild-to-moderate Alzheimer’s dementia at their last visit, known APOE4 genotype, died within the ensuing 24 months, and underwent neuropathologic evaluation. Main Outcomes and Measures Standardized histopathologic assessments of Alzheimer’s disease neuropathologic changes were the primary measures of interest in this study, specifically CERAD neuritic plaque density score, diffuse plaque density score, and Braak stage for neurofibrillary degeneration. Results 37% of APOE4 non-carriers and 13% of carriers with the primary clinical diagnosis of mild-to-moderate Alzheimer’s dementia had nonexistent or sparse neuritic plaques. 44% of the carriers and non-carriers with minimal neuritic plaques had Braak stage III–VI ratings and 38% met neuropathological criteria for other dementia-related diseases. Conclusions and relevance

  5. Detection of early stage atherosclerotic plaques using PET and CT fusion imaging targeting P-selectin in low density lipoprotein receptor-deficient mice

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Ikuko, E-mail: nakamuri@riken.jp [RIKEN Center for Molecular Imaging Science, Kobe (Japan); Department of Cardiovascular Medicine, Saga University, Saga (Japan); Hasegawa, Koki [RIKEN Center for Molecular Imaging Science, Kobe (Japan); Department of Pathology and Experimental Medicine, Kumamoto University, Kumamoto (Japan); Wada, Yasuhiro [RIKEN Center for Molecular Imaging Science, Kobe (Japan); Hirase, Tetsuaki; Node, Koichi [Department of Cardiovascular Medicine, Saga University, Saga (Japan); Watanabe, Yasuyoshi, E-mail: yywata@riken.jp [RIKEN Center for Molecular Imaging Science, Kobe (Japan)

    2013-03-29

    Highlights: ► P-selectin regulates leukocyte recruitment as an early stage event of atherogenesis. ► We developed an antibody-based molecular imaging probe targeting P-selectin for PET. ► This is the first report on successful PET imaging for delineation of P-selectin. ► P-selectin is a candidate target for atherosclerotic plaque imaging by clinical PET. -- Abstract: Background: Sensitive detection and qualitative analysis of atherosclerotic plaques are in high demand in cardiovascular clinical settings. The leukocyte–endothelial interaction mediated by an adhesion molecule P-selectin participates in arterial wall inflammation and atherosclerosis. Methods and results: A {sup 64}Cu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid conjugated anti-P-selectin monoclonal antibody ({sup 64}Cu-DOTA-anti-P-selectin mAb) probe was prepared by conjugating an anti-P-selectin monoclonal antibody with DOTA followed by {sup 64}Cu labeling. Thirty-six hours prior to PET and CT fusion imaging, 3 MBq of {sup 64}Cu-DOTA-anti-P-selectin mAb was intravenously injected into low density lipoprotein receptor-deficient Ldlr-/- mice. After a 180 min PET scan, autoradiography and biodistribution of {sup 64}Cu-DOTA-anti-P-selectin monoclonal antibody was examined using excised aortas. In Ldlr-/- mice fed with a high cholesterol diet for promotion of atherosclerotic plaque development, PET and CT fusion imaging revealed selective and prominent accumulation of the probe in the aortic root. Autoradiography of aortas that demonstrated probe uptake into atherosclerotic plaques was confirmed by Oil red O staining for lipid droplets. In Ldlr-/- mice fed with a chow diet to develop mild atherosclerotic plaques, probe accumulation was barely detectable in the aortic root on PET and CT fusion imaging. Probe biodistribution in aortas was 6.6-fold higher in Ldlr-/- mice fed with a high cholesterol diet than in those fed with a normal chow diet. {sup 64}Cu-DOTA-anti-P-selectin m

  6. Is plasma-soluble CD36 associated with density of atheromatous plaque and ankle-brachial index in early-onset coronary artery disease patients?

    Science.gov (United States)

    Rać, Monika; Krzystolik, Andrzej; Rać, Michał; Safranow, Krzysztof; Dziedziejko, Violetta; Goschorska, Marta; Poncyljusz, Wojciech; Chlubek, Dariusz

    2016-01-01

    CD36 is a major macrophage scavenger receptor for oxidised low-density lipoprotein particles. Soluble CD36 (sCD36) is circulating as a ligand-bound complex and may be present in microparticles shed from cells such as platelets, monocytes/macrophages, or adipocytes. Positive association of plasma sCD36 with insulin resistance has been reported, and it has been proposed that sCD36 might represent a marker of macrophage activation and inflammation leading to atherosclerosis. Recently we have identified an association between CD36 polymorphism and low thickness of atheromatous plaque, suggesting its protective effect against atherosclerosis development. To obtain insight into the relationship between plasma concentration of sCD36 and radiological parameters of atherosclerosis in patients with early-onset coronary artery disease (CAD). The study group comprised 70 clinically stable patients (18 women and 52 men) with early CAD (aged no more than 50 years for men and 55 years for women). Fasting blood sample was taken for serum glucose, lipid profile, ApoA1, ApoB, Lp(a), and plasma sCD36 protein measurements. Each subject's weight, height, waist and hip circumference, and systolic and diastolic blood pressure were measured, and the body mass index, waist-to-hip ratio, and mean arterial pressure were calculated. Doppler ultrasound examinations of carotid and peripheral arteries were performed in all patients. Thickness of intima-media complex (IMC) of common carotid (CCA) and brachial arteries, as well as density and thickness of atheromatous plaque at CCA bifurcation, were measured with M'Ath programme. Plasma concentrations of CD36 antigen were measured by ELISA. Correlations between quantitative variables and sCD36 plasma concentration were assessed with the Spearman rank correlation coefficient (Rs). Associations between qualitative variables and sCD36 plasma concentration were tested with the Mann-Whitney U test. We observed no significant correlations between sCD36

  7. Neurite outgrowth and branching of PC12 cells on very soft substrates sharply decreases below a threshold of substrate rigidity

    Science.gov (United States)

    Leach, Jennie B.; Brown, Xin Q.; Jacot, Jeffrey G.; Di Milla, Paul A.; Wong, Joyce Y.

    2007-06-01

    Rationally designed matrices for nerve tissue engineering and encapsulated cell therapies critically rely on a comprehensive understanding of neural response to biochemical as well as biophysical cues. Whereas biochemical cues are established mediators of neuronal behavior (e.g., outgrowth), physical cues such as substrate stiffness have only recently been recognized to influence cell behavior. In this work, we examine the response of PC12 neurites to substrate stiffness. We quantified and controlled fibronectin density on the substrates and measured multiple neurite behaviors (e.g., growth, branching, neurites per cell, per cent cells expressing neurites) in a large sample population. We found that PC12 neurons display a threshold response to substrate stiffness. On the softest substrates tested (shear modulus ~10 Pa), neurites were relatively few, short in length and unbranched. On stiffer substrates (shear modulus ~102-104 Pa), neurites were longer and more branched and a greater percentage of cells expressed neurites; significant differences in these measures were not found on substrates with a shear modulus >102 Pa. Based on these data and comparisons with published neurobiology and neuroengineering reports of neurite mechanotransduction, we hypothesize that results from studies of neuronal response to compliant substrates are cell-type dependent and sensitive to ligand density, sample size and the range of stiffness investigated.

  8. Presence of Striatal Amyloid Plaques in Parkinson’s Disease Dementia Predicts Concomitant Alzheimer’s Disease: Usefulness for Amyloid Imaging

    Science.gov (United States)

    Dugger, Brittany N.; Serrano, Geidy E.; Sue, Lucia I.; Walker, Douglas G.; Adler, Charles H.; Shill, Holly A.; Sabbagh, Marwan N.; Caviness, John N.; Hidalgo, Jose; Saxon-LaBelle, Megan; Chiarolanza, Glenn; Mariner, Monica; Henry-Watson, Jonette; Beach, Thomas G.

    2012-01-01

    Dementia is a frequent complication of Parkinson’s disease (PD). About half of PD dementia (PDD) is hypothesized to be due to progression of the underlying Lewy body pathology into limbic regions and the cerebral cortex while the other half is thought to be due to coexistent Alzheimer’s disease. Clinically, however, these are indistinguishable. The spread of amyloid plaques to the striatum has been reported to be a sensitive and specific indicator of dementia due to Alzheimer’s disease (AD). The purpose of the present study was to determine if the presence of striatal plaques might also be a useful indicator of the presence of diagnostic levels of AD pathology within PD subjects. We analyzed neuropathologically-confirmed cases of PD without dementia (PDND, N = 31), PDD without AD (PDD, N = 31) and PD with dementia meeting clinicopathological criteria for AD (PDAD, N =40). The minimum diagnostic criterion for AD was defined as including a clinical history of dementia, moderate or frequent CERAD cortical neuritic plaque density and Braak neurofibrillary stage III–VI. Striatal amyloid plaque densities were determined using Campbell-Switzer and Thioflavine S stains. Striatal plaque densities were significantly higher in PDAD compared to PDD (p<0.001). The presence of striatal plaques was approximately 80% sensitive and 80% specific for predicting AD. In comparison, the presence of cerebral cortex plaques alone was highly sensitive (100%) but had poor specificity (48% to 55%). The results suggest that striatal amyloid imaging may be clinically useful for making the distinction between PDD and PDAD. PMID:22924088

  9. Characterization of BASP1-mediated neurite outgrowth

    DEFF Research Database (Denmark)

    Korshunova, Irina; Caroni, Pico; Kolkova, Kateryna

    2008-01-01

    The brain acid-soluble protein BASP1 (CAP-23, NAP-22) belongs to the family of growth-associated proteins, which also includes GAP-43, a protein recently shown to regulate neural cell adhesion molecule (NCAM)-mediated neurite outgrowth. Here, the effects of BASP1 overexpression were investigated...... in PC12E2 cells and primary hippocampal neurons. BASP1 overexpression stimulated neurite outgrowth in both cell types. The effects of BASP1 and trans-homophilic NCAM interactions were additive, and BASP1-induced neurite outgrowth was not inhibited by ectopic expression of cytoplasmic NCAM domains...... on neurite outgrowth. Finally, coexpression experiments with dominant negative and wild-type versions of GAP-43 and BASP1 demonstrated that the two proteins could substitute for each other with respect to induction of NCAM-independent neurite outgrowth, whereas BASP1 was unable to replace the stimulatory...

  10. Conversion Disorder Presenting As Neuritic Leprosy

    Directory of Open Access Journals (Sweden)

    Sayal SK

    2000-01-01

    Full Text Available Conversion disorder is not normally listed amongst the conditions in differential diagnosis of leprosy neuropathy. A case conversion reaction who was initially diagnosed as neuritic leprosy is reported. Patient responded to narcosuggestion and psychotherapy.

  11. Computed Tomography Biomarkers of Vulnerable Coronary Plaques

    Directory of Open Access Journals (Sweden)

    Nyulas Tiberiu

    2016-12-01

    Full Text Available An unstable plaque has a high risk of thrombosis and at the same time for a fast progression of the stenosis degree. Also, “high-risk plaque” and “thrombosis-prone plaque” are used as synonym terms for characterization of a vulnerable plaque. The imaging biomarkers for vulnerable coronary plaques are considered to be spotty calcifications, active remodeling, low-density atheroma and the presence of a ring-like attenuation pattern, also known as the napkin-ring sign. Computed cardiac tomography can determine the plaque composition by assessing the plaque density, which is measured in Hounsfield units (HU. The aim of this manuscript was to provide an update about the most frequently used biomarkers of vulnerability in a vulnerable plaque with the help of computed cardiac tomography.

  12. Microvasculature of carotid atheromatous plaques: hemorrhagic plaques have dense microvessels with fenestrations to the arterial lumen.

    Science.gov (United States)

    Kurata, Mie; Nose, Masato; Shimazu, Yoshihito; Aoba, Takaaki; Kohada, Yuki; Yorioka, Soichiro; Suehiro, Satomi; Fukuoka, Erina; Matsumoto, Shirabe; Watanabe, Hideaki; Kumon, Yoshiaki; Okura, Takafumi; Higaki, Jitsuo; Masumoto, Junya

    2014-07-01

    Microvessels in atheromatous plaques are well known to play a role in plaque vulnerability associated with intraplaque hemorrhage, but their architecture remains unclear. The morphometry of the microvasculature and hemorrhage of human carotid atheromatous plaques (CAPs) were evaluated, and 3-dimensional (3D) reconstruction of the microvessels was performed. CAPs were obtained by endarterectomy in 42 patients. The specimens were analyzed using light microscopy. Plaque hemorrhage was defined as an area-containing red blood cells (>1 mm2). To determine the histopathologic features of plaque hemorrhage, the plaque area was divided into 4 regions: cap, shoulder, lipid/necrotic core, and media. Then, the density of microvessels and macrophages in each region was quantified. Two representative lesions with either hemorrhagic or nonhemorrhagic plaque were cut into 90 serial sections. The sections were double stained with anti-CD34 and anti-α smooth muscle actin antibodies, scanned using a digital microscope, and reconstructed using TRI-SRF2 software. The hemorrhagic plaques showed a higher density of microvessels than nonhemorrhagic plaques in the shoulder, cap, and lipid/necrotic core (P=.03, .009, and .001, respectively), and there was positive correlations between its density and macrophages in each regions (Pmicrovasculature of plaques with intraplaque hemorrhage was dense, some of which fenestrated to the arterial lumen. The pathologic 3D imaging revealed precise architecture of microvasculature of plaques. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  13. Olfactory ensheathing cell-neurite alignment enhances neurite outgrowth in scar-like cultures

    Science.gov (United States)

    Khankan, Rana R.; Wanner, Ina B.; Phelps, Patricia E.

    2015-01-01

    The regenerative capacity of the adult CNS neurons after injury is strongly inhibited by the spinal cord lesion site environment that is composed primarily of the reactive astroglial scar and invading meningeal fibroblasts. Olfactory ensheathing cell (OEC) transplantation facilitates neuronal survival and functional recovery after a complete spinal cord transection, yet the mechanisms by which this recovery occurs remain unclear. We used a unique multicellular scar-like culture model to test if OECs promote neurite outgrowth in growth inhibitory areas. Astrocytes were mechanically injured and challenged by meningeal fibroblasts to produce key inhibitory elements of a spinal cord lesion. Neurite outgrowth of postnatal cerebral cortical neurons was assessed on three substrates: quiescent astrocyte control cultures, reactive astrocyte scar-like cultures, and scar-like cultures with OECs. Initial results showed that OECs enhanced total neurite outgrowth of cortical neurons in a scar-like environment by 60%. We then asked if the neurite growth-promoting properties of OECs depended on direct alignment between neuronal and OEC processes. Neurites that aligned with OECs were nearly three times longer when they grew on inhibitory meningeal fibroblast areas and twice as long on reactive astrocyte zones compared to neurites not associated with OECs. Our results show that OECs can independently enhance neurite elongation and that direct OEC-neurite cell contact can provide a permissive substrate that overcomes the inhibitory nature of the reactive astrocyte scar border and the fibroblast-rich spinal cord lesion core. PMID:25863021

  14. Pure neuritic leprosy: Current status and relevance.

    Science.gov (United States)

    Rao, P Narasimha; Suneetha, Sujai

    2016-01-01

    Pure neuritic leprosy has always been an enigma due to its clinical and management ambiguities. Although only the Indian Association of Leprologist's classification recognizes 'pure neuritic leprosy' as a distinct sub group of leprosy, cases nonetheless are reported from various countries of Asia, Africa, South America and Europe, indicating its global relevance. It is important to maintain pure neuritic leprosy as a subgroup as it constitutes a good percentage of leprosy cases reported from India, which contributes to more than half of global leprosy numbers. Unfortunately, a high proportion of these patients present with Grade 2 disability at the time of initial reporting itself due to the early nerve involvement. Although skin lesions are absent by definition, when skin biopsies were performed from the skin along the distribution of the affected nerve, a proportion of patients demonstrated leprosy pathology, revealing sub-clinical skin involvement. In addition on follow-up, skin lesions are noted to develop in up to 20% of pure neuritic leprosy cases, indicating its progression to manifest cutaneous disease. Over the decades, the confirmation of diagnosis of pure neuritic leprosy has been subjective, however, with the arrival and use of high-resolution ultrasonography (HRUS) for nerve imaging, we have a tool not only to objectively measure and record the nerve thickening but also to assess the morphological alterations in the nerve including echo texture, fascicular pattern and vascularity. Management of pure neuritic leprosy requires multidrug therapy along with appropriate dose of systemic corticosteroids, for both acute and silent neuritis. Measures for pain relief, self-care of limbs and physiotherapy are important to prevent as well as manage disabilities in this group of patients.

  15. Pure neuritic leprosy: Current status and relevance

    Directory of Open Access Journals (Sweden)

    P Narasimha Rao

    2016-01-01

    Full Text Available Pure neuritic leprosy has always been an enigma due to its clinical and management ambiguities. Although only the Indian Association of Leprologist's classification recognizes 'pure neuritic leprosy' as a distinct sub group of leprosy, cases nonetheless are reported from various countries of Asia, Africa, South America and Europe, indicating its global relevance. It is important to maintain pure neuritic leprosy as a subgroup as it constitutes a good percentage of leprosy cases reported from India, which contributes to more than half of global leprosy numbers. Unfortunately, a high proportion of these patients present with Grade 2 disability at the time of initial reporting itself due to the early nerve involvement. Although skin lesions are absent by definition, when skin biopsies were performed from the skin along the distribution of the affected nerve, a proportion of patients demonstrated leprosy pathology, revealing sub-clinical skin involvement. In addition on follow-up, skin lesions are noted to develop in up to 20% of pure neuritic leprosy cases, indicating its progression to manifest cutaneous disease. Over the decades, the confirmation of diagnosis of pure neuritic leprosy has been subjective, however, with the arrival and use of high-resolution ultrasonography (HRUS for nerve imaging, we have a tool not only to objectively measure and record the nerve thickening but also to assess the morphological alterations in the nerve including echo texture, fascicular pattern and vascularity. Management of pure neuritic leprosy requires multidrug therapy along with appropriate dose of systemic corticosteroids, for both acute and silent neuritis. Measures for pain relief, self-care of limbs and physiotherapy are important to prevent as well as manage disabilities in this group of patients.

  16. Plaque complement activation and cognitive loss in Alzheimer's disease

    Science.gov (United States)

    Loeffler, David A; Camp, Dianne M; Bennett, David A

    2008-01-01

    Background Complement activation is increased in Alzheimer's disease (AD), but its significance is unclear. The objective of this study was to determine the relationship between complement activation and cognition during the development of AD. Methods iC3b, C9, Bielschowsky, and Gallyas staining was performed on aged normal (n = 17), mild cognitively impaired (n = 12), and AD (n = 17–18) inferior temporal gyrus specimens. Plaques were counted in 10× fields with high numbers of Bielschowsky-stained plaques. One-way ANOVA was used to determine between-group differences for plaque counts and measures of cognitive function, and linear regression was used to evaluate global cognition as a function of Bielschowsky-stained plaques. Terms for iC3b- and C9-stained plaques were then added sequentially as additional predictors in a "mediation analysis" model. Results Complement was detected on plaques in all groups, and on neurofibrillary tangles only in AD specimens. iC3b, C9, and Bielschowsky-stained plaque counts increased 2.5- to 3-fold in AD vs. other groups (all p ≤ 0.01). C9 staining was present on some diffuse plaques, as well as on neuritic plaques. Bielschowsky-stained and complement-stained plaque counts were highly correlated, and were negatively correlated with cognitive measures. When the Bielschowsky plaque count was used as a predictor, its correlations with cognitive measures were statistically significant, but when iC3b and C9 plaque counts were added as additional predictors, these correlations were no longer significant. This loss of significance was attributed to multicollinearity, i.e., high correlations between Bielschowsky-stained and complement-stained plaque counts. Conclusion Both early-stage (iC3b) and late-stage (C9) complement activation occurs on neocortical plaques in subjects across the cognitive spectrum; contrary to previous reports, C9 is present on some diffuse plaques. Because of high correlations between complement-stained and

  17. Hydrogel Design for Supporting Neurite Outgrowth and Promoting Gene Delivery to Maximize Neurite Extension

    Science.gov (United States)

    Shepard, Jaclyn A.; Stevans, Alyson C.; Holland, Samantha; Wang, Christine E.; Shikanov, Ariella; Shea, Lonnie D.

    2012-01-01

    Hydrogels capable of gene delivery provide a combinatorial approach for nerve regeneration, with the hydrogel supporting neurite outgrowth and gene delivery inducing the expression of inductive factors. This report investigates the design of hydrogels that balance the requirements for supporting neurite growth with those requirements for promoting gene delivery. Enzymatically-degradable PEG hydrogels encapsulating dorsal root ganglia explants, fibroblasts, and lipoplexes encoding nerve growth factor were gelled within channels that can physically guide neurite outgrowth. Transfection of fibroblasts increased with increasing concentration of Arg-Gly-Asp (RGD) cell adhesion sites and decreasing PEG content. The neurite length increased with increasing RGD concentration within 10% PEG hydrogels, yet was maximal within 7.5% PEG hydrogels at intermediate RGD levels. Delivering lipoplexes within the gel produced longer neurites than culture in NGF-supplemented media or co-culture with cells exposed to DNA prior to encapsulation. Hydrogels designed to support neurite outgrowth and deliver gene therapy vectors locally may ultimately be employed to address multiple barriers that limit regeneration. PMID:22038654

  18. Nerve growth factor promotes neurite outgrowth in guinea pig myenteric plexus ganglia.

    Science.gov (United States)

    Mulholland, M W; Romanchuk, G; Lally, K; Simeone, D M

    1994-10-01

    Nerve growth factor (NGF) has important developmental actions in both central and peripheral nervous systems. Primary cultures of neonatal guinea pig myenteric plexus ganglia were used to examine the ability of NGF to stimulate morphological development in enteric neurons. NGF, in the presence of a serum-free medium, produced dose-dependent increases in neurite density, significant at 1 ng/ml and maximal at 100 ng/ml (4.5-fold increase vs. control). Maximum neurite length was also significantly increased at 1 ng/ml, with maximal effects at 100 ng/ml. Coincubation of NGF (50 ng/ml) with monoclonal NGF antibodies abolished increases in both neurite density (128 +/- 19 processes/mm for control, 369 +/- 19 for NGF, 183 +/- 28 for NGF+monoclonal antibodies) and neurite length. Exposure of enteric neurons to low concentrations of NGF (1 ng/ml) was also associated with increased mRNA levels for cytoskeletal genes. alpha-Tubulin mRNA levels were increased 3.9 +/- 0.7 times basal at 48 h. mRNA levels for microtubule-associated protein 2 were increased threefold at 48 h of NGF incubation. NGF demonstrates activities in cultured enteric ganglia that stimulate morphological development.

  19. Formation and maintenance of Alzheimer’s disease β-amyloid plaques in the absence of microglia

    Science.gov (United States)

    Grathwohl, Stefan A; Kälin, Roland E; Bolmont, Tristan; Prokop, Stefan; Winkelmann, Georg; Kaeser, Stephan A; Odenthal, Jörg; Radde, Rebecca; Eldh, Therese; Gandy, Sam; Aguzzi, Adriano; Staufenbiel, Matthias; Mathews, Paul M; Wolburg, Hartwig; Heppner, Frank L; Jucker, Mathias

    2016-01-01

    In Alzheimer’s disease, microglia cluster around β-amyloid deposits, suggesting that these cells are important for amyloid plaque formation, maintenance and/or clearance. We crossed two distinct APP transgenic mouse strains with CD11b-HSVTK mice, in which nearly complete ablation of microglia was achieved for up to 4 weeks after ganciclovir application. Neither amyloid plaque formation and maintenance nor amyloid-associated neuritic dystrophy depended on the presence of microglia. PMID:19838177

  20. Dual pathways regulate neurite outgrowth in enteric ganglia.

    Science.gov (United States)

    Simeone, D M; Romanchuk, G; Mulholland, M W

    1994-10-01

    Primary cultures of guinea pig myenteric plexus ganglia were used to examine the ability of agents that activate adenylate cyclase or mimic intracellular adenosine 3',5'-cyclic monophosphate (cAMP) to stimulate morphological growth. Dose-dependent increases in neurite length and density were produced in enteric neuronal cultures by forskolin (212% of control), cholera toxin (356% of control), or the permeant cAMP analogues 8-bromoadenosine 3',5'-cyclic monophosphate and dibutyryl cAMP. (R)-p-adenosine 3',5'-cyclic monophosphorothioate, an inhibitor of cAMP-dependent kinases, blocked the growth-promoting effects of cAMP analogues but not of nerve growth factor (NGF). Activation of cAMP-dependent signaling pathways also increased production of mRNA for alpha-tubulin and microtubule-associated protein 2. Dual pathways, regulated by NGF and cAMP-dependent protein kinases, influence growth signaling in enteric ganglia.

  1. Plaque mineralisation in vitro.

    Science.gov (United States)

    Wong, L

    1998-03-01

    Dental calculus is plaque mineralised by deposition of calcium and phosphate resulting from interactions between the oral microbial plaque flora and components of oral fluids. An artificial-mouth microcosm dental plaque culture system has been developed to study aspects of plaque mineralisation, including pH control. Five plaques were grown from saliva under simulated oral conditions in a mucin-containing medium, and sucrose was applied to mimic meals. The plaques were mineralised with a urea-based, calcium-phosphate-monofluorophosphate-urea (CPMU) mineralising solution. Alkaline pH oscillations were generated by the plaques in response to CPMU applications, and an acidic oscillation followed sucrose applications. Plaque mineralisation by the CPMU procedure was almost totally dependent on the urea present in the mineralising solution, but total mineralisation also increased as the resting pH increased as a result of urea in the medium. Following four CPMU applications with a sucrose application every 12 hours improved plaque viability and mineralisation. The plaque mineral formed resembled a carbonated hydroxyapatite; other potential calcium phosphate minerals were undetectable except for calcium carbonate. A wide range of mineral deposition patterns in plaque were seen by electron microscopy.

  2. Neuritic Patient at Sanglah General Hospital Denpasar

    Directory of Open Access Journals (Sweden)

    Ni Putu Dita-Rinjani

    2012-05-01

    Full Text Available Objective: Treatment of optic neuritic as recommended by the Optic Neuritic Treatment Trial (ONTT was intravenous methylprednisolon followed by oral prednisone. This study aims to describe  characteristics and response to intravenous methylprednisolon followed by oral prednisone treatment of optic neuritic patient in Sanglah General Hospital Denpasar. Method: This report is an analytical cross sectional study. Data were collected retrospectively from medical report of optic neuritic patient who came to Sanglah General Hospital during a period of January 1st 2010 until December 31st 2011. Patient characteristics were analyzed with descriptive analyses and presented as frequency, percentage, mean and standar deviation. Visual acuity and contrast sensitivity improvement after intravenous methylprednisolon followed by oral prednisone treatment were statistically analyzed with Wilcoxon test Results:  Optic neuritic were found in twenty-three patients (33 eyes, majority was in age group of 15-40 years (56.5% with female predominance (65.2% and unilateral involvement was 56.3%. Mean onset patient presented to the hospital was 21.7±2.21 days and the most common symptom was decreasing vision (87.9%.  The majority of patient presented with papillitis (54.5%, totally color blindness found in 39.4% eyes, and the type of visual field defect at presentation was central scotoma (18.2%. All cases show lesion of optic nerve from visual evoked potential (VEP examination and magnetic resonance imaging (MRI shows normal results (39.1% patient. The mean of pretreatment logMAR visual acuity and contrast sensitivity were significant improve after treatment from 1.59±0.47 to 0.59±0.62 (p=0.0001 and 0.31±0.56 to 1.25±0.56 (p=0.0001, respectively. All cases in this study were idiopathic. Recurrences were seen in 2 eyes and none of patient had clinical features suggestive of multiple sclerosis. Conclusions: Visual acuity and contrast sensitivity improvement

  3. Ultrastructural study of florid plaques in variant Creutzfeldt-Jakob disease: a comparison with amyloid plaques in kuru, sporadic Creutzfeldt-Jakob disease and Gerstmann-Sträussler-Scheinker disease.

    Science.gov (United States)

    Sikorska, B; Liberski, P P; Sobów, T; Budka, H; Ironside, J W

    2009-02-01

    Although the histological features of the amyloid plaques in variant Creutzfeldt-Jakob disease (vCJD) are distinct from those in other forms of prion disease [kuru, sporadic Creutzfeldt-Jakob disease (sCJD) and Gerstmann-Sträussler-Scheinker disease (GSS)], their ultrastructural features have only been described in a single case report. To study vCJD plaques systematically and compare them with plaques in kuru, sCJD, GSS and Alzheimer disease (AD). Amyloid plaques were studied by transmission electron microscopy and image analysis in five cases of vCJD, three cases of GSS, two cases of sCJD, one case of kuru and five cases of AD. Immunohistochemistry was performed on paraffin sections from one case of vCJD, two cases of GSS, one case of kuru and two cases of sCJD. The florid plaques in vCJD were either compact or more diffuse; in both forms, the radiating fibrils were organized into thick 'tongues', in contrast to kuru plaques. Dystrophic neurites (DNs) containing lysosomal electron-dense bodies or vesicles surrounded florid plaques. Microglial cells were found within florid plaques; occasional amyloid fibrils were identified in membrane-bound pockets of microglial cells. In vCJD, there was significant tau immunoreactivity in DNs around florid plaques while, in sCJD, GSS and kuru, minimal tau immunoreactivity was observed around plaques. The ultrastructure of the florid plaques and DNs in vCJD is more reminiscent of neuritic plaques in AD than kuru or multicentric plaques. These findings may reflect differences both in the strains of the transmissible agents responsible for these disorders and in host factors.

  4. Plaque-Associated Local Toxicity Increases over the Clinical Course of Alzheimer Disease

    Science.gov (United States)

    Serrano-Pozo, Alberto; Betensky, Rebecca A.; Frosch, Matthew P.; Hyman, Bradley T.

    2017-01-01

    Amyloid (senile) plaques, one of the two pathologic hallmarks of Alzheimer disease (AD), are associated with dystrophic neurites and glial responses, both astrocytic and microglial. Although plaque burden remains relatively stable through the clinical course of AD, whether these features of local plaque toxicity continue to worsen over the course of the disease is unclear. We performed an unbiased plaque-centered quantification of SMI312+ dystrophic neurites, GFAP+ reactive astrocytes, and IBA1+ and CD68+ activated microglia in randomly selected dense-core (Thioflavin-S+) plaques from the temporal neocortex of 40 AD subjects with a symptom duration ranging from 4 to 20 years, and nine nondemented control subjects with dense-core plaques. Dystrophic neurites (Kendall τ = 0.34, P = 0.001), reactive astrocytes (Kendall τ = 0.30, P = 0.003), and CD68+ (Kendall τ = 0.48, P < 0.0001), but not IBA1 microglia (Kendall τ = 0.045, P = 0.655), exhibited a significant positive correlation with symptom duration. When excluding control subjects, only the positive association between CD68+ microglia and symptom duration remained significant (Kendall τ = 0.39, P = 0.0003). The presence of the APOEε4 allele did not affect these results. We conclude that plaques exert an increasing toxicity in the surrounding neuropil over the clinical course of AD, thereby potentially contributing to cognitive decline. PMID:26687817

  5. Nimodipine enhances neurite outgrowth in dopaminergic brain slice co-cultures.

    Science.gov (United States)

    Sygnecka, Katja; Heine, Claudia; Scherf, Nico; Fasold, Mario; Binder, Hans; Scheller, Christian; Franke, Heike

    2015-02-01

    Calcium ions (Ca(2+)) play important roles in neuroplasticity and the regeneration of nerves. Intracellular Ca(2+) concentrations are regulated by Ca(2+) channels, among them L-type voltage-gated Ca(2+) channels, which are inhibited by dihydropyridines like nimodipine. The purpose of this study was to investigate the effect of nimodipine on neurite growth during development and regeneration. As an appropriate model to study neurite growth, we chose organotypic brain slice co-cultures of the mesocortical dopaminergic projection system, consisting of the ventral tegmental area/substantia nigra and the prefrontal cortex from neonatal rat brains. Quantification of the density of the newly built neurites in the border region (region between the two cultivated slices) of the co-cultures revealed a growth promoting effect of nimodipine at concentrations of 0.1μM and 1μM that was even more pronounced than the effect of the growth factor NGF. This beneficial effect was absent when 10μM nimodipine were applied. Toxicological tests revealed that the application of nimodipine at this higher concentration slightly induced caspase 3 activation in the cortical part of the co-cultures, but did neither affect the amount of lactate dehydrogenase release or propidium iodide uptake nor the ratio of bax/bcl-2. Furthermore, the expression levels of different genes were quantified after nimodipine treatment. The expression of Ca(2+) binding proteins, immediate early genes, glial fibrillary acidic protein, and myelin components did not change significantly after treatment, indicating that the regulation of their expression is not primarily involved in the observed nimodipine mediated neurite growth. In summary, this study revealed for the first time a neurite growth promoting effect of nimodipine in the mesocortical dopaminergic projection system that is highly dependent on the applied concentrations. Copyright © 2014 ISDN. Published by Elsevier Ltd. All rights reserved.

  6. The combinatorics of neurite self-avoidance.

    Science.gov (United States)

    Forbes, Elizabeth M; Hunt, Jonathan J; Goodhill, Geoffrey J

    2011-11-01

    During neural development in Drosophila, the ability of neurite branches to recognize whether they are from the same or different neurons depends crucially on the molecule Dscam1. In particular, this recognition depends on the stochastic acquisition of a unique combination of Dscam1 isoforms out of a large set of possible isoforms. To properly interpret these findings, it is crucial to understand the combinatorics involved, which has previously been attempted only using stochastic simulations for some specific parameter combinations. Here we present closed-form solutions for the general case. These reveal the relationships among the key variables and how these constrain possible biological scenarios.

  7. Pea3 transcription factor promotes neurite outgrowth

    Directory of Open Access Journals (Sweden)

    BASAK eKANDEMIR

    2014-06-01

    Full Text Available Pea3 subfamily of ETS transcription factors consist of three major proteins, Pea3, ERM and ER81. Although important for many different tissues that exhibit branching morphogenesis, the function of Pea3 family in nervous system development and regeneration is only beginning to unfold. In this study, we provide evidence that Pea3 can directs neurite extension and axonal outgrowth in different model systems, and that Serine 90 is important for this function. We have also identified neurofilament-L and neurofilament-M as two putative novel targets for Pea3.

  8. Plaque Type Eryrhema Nodosum

    Directory of Open Access Journals (Sweden)

    Radha Mittal

    1987-01-01

    Full Text Available Three young females developed plaque type erythema nodosum. The underlying causes in them were tuberculosis chest, recurrent furunculosis and malaria respectively. All the three cases were under treatment at the time of development of erythema nodosum plaques and the onset was acute.

  9. The affection of the disturbance of the hydrodynamics of blood in case of stress on pathological increase of level of low density lipoproteins in blood. The formation of cylindrical plaques, and their participation in the development of acute ischemic disorders of heart and brain.

    Science.gov (United States)

    Rusanov, S E

    2017-09-01

    In this article is given the new insight about the affection of stress on the increase of level of low density lipoproteins (LDL) in the blood, which is connected with the disturbance of hydrodynamics in the bloodstream, the attention was paid to the cylindrical cholesterol plaque, and it's classification. The disturbance of hydrodynamics of blood under the stress leads to the formation of a cylindrical cholesterol plaque, which repeats the contour of the vessel, and leads to the ischemic disorders of the heart and brain. The cylindrical cholesterol plaque goes through several stages of development: friable, yielding, dense, old. In the case of destruction of friable, fresh cholesterol plaque, releases a big quantity of low-density lipoproteins. This leads to the pathological increase of level of LDL in the blood. In the case of long disturbance of hydrodynamics, occurs the formation of strong links between low-density lipoproteins. Yielding cholesterol plaque is formed. Further maturation of cylindrical cholesterol plaque, leads to it's densifying and damage. We may emphasize, that short periods of strong contraction and expansion of vessels lead to the increase of level of LDL in the blood. Self-dependent restoration of normal level of LDL in blood occurs in the case of restoration of pressure in the limits of numbers, which are specific for particular person, and which don't exceed the physiological standard. Among patients with long duration of stress, the duration of vasospasm increases. LDL, without having a possibility to crumble, begin to stick together and form the yielding cylindrical plaque. It is characterized by having of not so strong connection with the vascular wall, and maintains only at the expanse of iteration of the vascular wall, it has cylindrical shape, is elastic and yellow. The thickness and length of walls depends on the degree of cross-clamping during the time of formation of yielding cylindrical plaque. In the case of stopping of spasm

  10. Serial changes of coronary atherosclerotic plaque: Assessment with 64-slice multi-detector computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun Young; Kang, Doo Kyoung; Sun, Joo Sung; Choi, So Yeon [Ajou University School of Medicine, Suwon (Korea, Republic of)

    2013-12-15

    Evaluate the progression of coronary atherosclerotic plaque during follow-up, and its association with cardiovascular risk factors. Fifty-six atherosclerotic patients with plaque were enrolled in this retrospective study. Patient's plaque was detected on repeat 64-slice multidetector CT scans with a mean interval of 25 ± 10 months changes in calcified and non-calcified plaque volumes and cardiovascular risk factors were assessed over time. Absolute and relative changes in plaque volume were compared, and the association between rapid progression and cardiovascular risk factors was determined. Diameter of the stenosis, length, calcified and non-calcified lesion plaque volumes increased significantly on follow-up CT. Absolute and relative annual changes in plaque volumes were significantly greater in non-calcified plaque (median, 22.7 mm{sup 3}, 90.4%) than in calcified plaque (median, 0.7 mm{sup 3}, 0%). Obesity, smoking, hypertension, hypercholesterolemia, and low high-density lipoprotein were significant predictors of progression of non-calcified plaque. Progression of calcified plaque was not associated with any cardiovascular risk factors. Coronary plaque volume increased significantly on follow-up CT. The rate of progression is related to non-calcified plaque than to calcified plaque. Cardiovascular risk factors are independently associated with the rapid progression of non-calcified plaque volume, but not associated with the progression of calcified plaque.

  11. Mechanical stress activates neurites and somata of myenteric neurons

    Directory of Open Access Journals (Sweden)

    Eva Maria Kugler

    2015-09-01

    Full Text Available The particular location of myenteric neurons, sandwiched between the 2 muscle layers of the gut, implies that their somata and neurites undergo mechanical stress during gastrointestinal motility. Existence of mechanosensitive enteric neurons (MEN is undoubted but many of their basic features remain to be studied. In this study, we used ultra-fast neuroimaging to record activity of primary cultured myenteric neurons of guinea pig and human intestine after von Frey hair evoked deformation of neurites and somata. Independent component analysis was applied to reconstruct neuronal morphology and follow neuronal signals. Of the cultured neurons 45% (114 out of 256, 30 guinea pigs responded to neurite probing with a burst spike frequency of 13.4 Hz. Action potentials generated at the stimulation site invaded the soma and other neurites. Mechanosensitive sites were expressed across large areas of neurites. Many mechanosensitive neurites appeared to have afferent and efferent functions as those that responded to deformation also conducted spikes coming from the soma. Mechanosensitive neurites were also activated by nicotine application. This supported the concept of multifunctional MEN. 14% of the neurons (13 out of 96, 18 guinea pigs responded to soma deformation with burst spike discharge of 17.9 Hz. Firing of MEN adapted rapidly (RAMEN, slowly (SAMEN or ultra-slowly (USAMEN. The majority of MEN showed SAMEN behavior although significantly more RAMEN occurred after neurite probing. Cultured myenteric neurons from human intestine had similar properties. Compared to MEN, dorsal root ganglion neurons were activated by neurite but not by soma deformation with slow adaptation of firing. We demonstrated that MEN exhibit specific features very likely reflecting adaptation to their specialized functions in the gut.

  12. Mathematical models for atherosclerotic plaque evolution

    NARCIS (Netherlands)

    Bulelzai, M.A.K.

    2013-01-01

    Atherosclerosis is a disease in which low density lipoproteins (LDL) accumulate in the arterial wall due to an inflammatory response, which is triggered by the oxidation of LDL molecules that are already present in the arterial wall. Progression of atherosclerotic plaques involves many components

  13. High Field Atherosclerotic Plaque MRI

    OpenAIRE

    Yuan, Chun; Wang, Jinnan; Balu, Niranjan

    2012-01-01

    Manifestations of atherosclerotic plaque in different arterial beds range from perfusion deficits to overt ischemia such as stroke and myocardial infarction. Atherosclerotic plaque composition is known to be associated with its propensity to rupture and cause vascular events. MRI of atherosclerotic plaque using clinical 1.5T scanners can detect plaque composition. Plaque MRI at higher field strengths offers both opportunities and challenges to improving the high spatial-resolution and contras...

  14. Carotid plaque, intima-media thickness, and incident aortic stenosis

    DEFF Research Database (Denmark)

    Martinsson, Andreas; Östling, Gerd; Persson, Margaretha

    2014-01-01

    OBJECTIVE: Aortic stenosis (AS) shares risk factors with atherosclerotic vascular disease. Carotid intima-media thickness (IMT) and plaque may reflect the cumulative damage from exposure to different atherosclerotic risk factors. We examined the relationship of carotid IMT and plaque with incident...... AS in a prospective population-based study. APPROACH AND RESULTS: A random sample of participants (age, 45-68 years) in the population-based Malmö Diet and Cancer Study underwent B-mode ultrasound with measurements of IMT and the presence of plaque in the common carotid artery (n=5079). Potential risk factors......-density lipoprotein cholesterol, hypertension, diabetes mellitus, smoking, C-reactive protein, plaque, and IMT. In contrast, high-density lipoprotein cholesterol, triglycerides, height, and leukocyte count were not significantly associated with AS (P>0.05). After adjustments, IMT, plaque, age, smoking, C...

  15. Merlin inhibits neurite outgrowth in the CNS.

    Science.gov (United States)

    Schulz, Alexander; Geissler, Katja J; Kumar, Sujeet; Leichsenring, Gregor; Morrison, Helen; Baader, Stephan L

    2010-07-28

    The neurofibromatosis type 2 gene product merlin is known to provoke gliogenic tumors as a result of its mutagenic loss. Merlin's physiological anti-mitogenic function makes it unique among its ezrin-radixin-moesin (ERM) family members. Although ERM proteins and merlin are known to be expressed in glial cells of the peripheral nervous system and CNS, the neuronal expression pattern and function of merlin have been less well investigated. We report here expression of merlin in developing and mature neurons of the murine CNS. Within cerebellar Purkinje cells (PCs), merlin was localized in the soma, sprouting dendrites and axons. Merlin expression in PCs was high during the period of initial dendrite regression and declined during later phases of dendrite elongation. Consistently, merlin expression in vivo was increased in Engrailed-2-overexpressing PCs, which are characterized by a reduced dendritic extension. Furthermore, overexpression of merlin in dissociated cerebellar cultures and in neurogenic P19 cells caused a significant decline in neurite outgrowth, while, conversely, inhibition of merlin expression increased process formation. This effect was dependent on phosphorylation of serine 518 and involved the inactivation of the growth-promoting GTPase Rac. We thus provide evidence that merlin plays a pivotal role in controlling the neuronal wiring in the developing CNS.

  16. Neurite, a finite difference large scale parallel program for the simulation of electrical signal propagation in neurites under mechanical loading.

    Directory of Open Access Journals (Sweden)

    Julián A García-Grajales

    Full Text Available With the growing body of research on traumatic brain injury and spinal cord injury, computational neuroscience has recently focused its modeling efforts on neuronal functional deficits following mechanical loading. However, in most of these efforts, cell damage is generally only characterized by purely mechanistic criteria, functions of quantities such as stress, strain or their corresponding rates. The modeling of functional deficits in neurites as a consequence of macroscopic mechanical insults has been rarely explored. In particular, a quantitative mechanically based model of electrophysiological impairment in neuronal cells, Neurite, has only very recently been proposed. In this paper, we present the implementation details of this model: a finite difference parallel program for simulating electrical signal propagation along neurites under mechanical loading. Following the application of a macroscopic strain at a given strain rate produced by a mechanical insult, Neurite is able to simulate the resulting neuronal electrical signal propagation, and thus the corresponding functional deficits. The simulation of the coupled mechanical and electrophysiological behaviors requires computational expensive calculations that increase in complexity as the network of the simulated cells grows. The solvers implemented in Neurite--explicit and implicit--were therefore parallelized using graphics processing units in order to reduce the burden of the simulation costs of large scale scenarios. Cable Theory and Hodgkin-Huxley models were implemented to account for the electrophysiological passive and active regions of a neurite, respectively, whereas a coupled mechanical model accounting for the neurite mechanical behavior within its surrounding medium was adopted as a link between electrophysiology and mechanics. This paper provides the details of the parallel implementation of Neurite, along with three different application examples: a long myelinated axon

  17. Atopic keratinocytes induce increased neurite outgrowth in a coculture model of porcine dorsal root ganglia neurons and human skin cells.

    Science.gov (United States)

    Roggenkamp, Dennis; Falkner, Susanne; Stäb, Franz; Petersen, Marlen; Schmelz, Martin; Neufang, Gitta

    2012-07-01

    Skin of patients suffering from atopic eczema displays a higher epidermal nerve fiber density, associated with neurogenic inflammation and pruritus. Using an in vitro coculture system, allowing a spatially compartmented culture of somata from porcine dorsal root ganglion neurons and human primary skin cells, we investigated the influence of dermal fibroblasts and keratinocytes on neurite outgrowth. In comparison with dermal fibroblasts, keratinocytes induced more branched and less calcitonin gene-related peptide (CGRP)-immunoreactive nerve fibers. By adding neutralizing antibodies, we showed that nerve growth factor (NGF) and glial cell-line-derived neurotrophic factor (GDNF) are pivotal neurotrophic factors of skin cell-induced neurite outgrowth. Keratinocytes and dermal fibroblasts secreted different ratios of neurotrophic factors, influencing morphology and CGRP immunoreactivity of neurites. To investigate changes of the peripheral nervous system in the pathogenesis of atopic eczema in vitro, we analyzed neurite outgrowth mediated by atopic skin cells. Atopic keratinocytes produced elevated levels of NGF and mediated an increased outgrowth of CGRP-positive sensory fibers. Our results demonstrate the impact of dermal fibroblasts and keratinocytes on skin innervation and emphasize the role of keratinocytes as key players of hyperinnervation in atopic eczema.

  18. Murine versus human apolipoprotein E4: differential facilitation of and co-localization in cerebral amyloid angiopathy and amyloid plaques in APP transgenic mouse models

    OpenAIRE

    Liao, Fan; Zhang, Tony J.; Jiang, Hong; Lefton, Katheryn B; Robinson, Grace O.; Vassar, Robert; Sullivan, Patrick M.; Holtzman, David M.

    2015-01-01

    Introduction Amyloid ? (A?) accumulates in the extracellular space as diffuse and neuritic plaques in Alzheimer?s disease (AD). A? also deposits on the walls of arterioles as cerebral amyloid angiopathy (CAA) in most cases of AD and sometimes independently of AD. Apolipoprotein E (apoE) ?4 is associated with increases in both A? plaques and CAA in humans. Studies in mouse models that develop A? deposition have shown that murine apoE and human apoE4 have different abilities to facilitate plaqu...

  19. Lipids and carotid plaque in the Northern Manhattan Study (NOMAS

    Directory of Open Access Journals (Sweden)

    Sacco Ralph L

    2009-12-01

    Full Text Available Abstract Background Lipids, particularly low-density (LDL and high-density (HDL lipoproteins, are associated with increased risk of stroke and cardiovascular disease, probably due to atherosclerosis. The objective of this cross-sectional analysis was to investigate the relation between blood lipids and carotid plaque. Methods As part of a prospective population-based study to determine the incidence and risk factors of stroke in a multiethnic population, we evaluated 1804 participants with lipid measurements and B-mode ultrasound of carotid arteries (mean age 69 +/- 10 years; 40% men; 51% Hispanic, 26% black, 23% white. The association between lipid parameters and carotid plaque was analyzed by multiple logistic regression. Results Plaque was present in 61% of participants. Mean total cholesterol was 202 +/- 41 mg/dl. After controlling for other lipid parameters, demographics, and risk factors, the only cholesterol subfraction associated with carotid plaque was LDL (OR per standard deviation (SD = 1.14, 95% CI 1.02-1.27. Neither HDL nor triglycerides independently predicted carotid plaque. Apolipoprotein B (ApoB was also associated with risk of plaque (OR per SD = 1.29, 95% CI 1.03-1.60. Apolipoprotein A-I (apoA-1 was associated with a decrease in multiple plaques (OR per SD = 0.76, 95% CI 0.60-0.97, while lipoprotein a was associated with an increased risk of multiple plaques (OR per SD = 1.31, 95% CI 1.03-1.66. ApoB:ApoA-I had the strongest relation with carotid plaque (OR per SD = 1.35, 95% CI 1.08-1.69. Conclusions Among the common lipid parameters, LDL has the strongest relation with carotid plaque. Other lipid precursor proteins such as ApoB and ApoA-I may be stronger predictors of subclinical atherosclerosis, however, and better targets for treatment to reduce plaque formation and risk of cerebrovascular disease.

  20. The vulnerable plaque: From plaque instability towards thrombus instability

    NARCIS (Netherlands)

    Li, X.

    2014-01-01

    Acuut coronair syndroom wordt meestal veroorzaakt door het scheuren van een atherosclerotische plaque in combinatie met (afsluitende) trombusvorming in de kransslagader. Plaque ruptuur en trombotische occlusie treden vaak niet gelijktijdig op, en het tijdstip van het ontstaan van klinische klachten

  1. Dental plaque identification at home

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003426.htm Dental plaque identification at home To use the sharing features on this page, please enable JavaScript. Plaque is a sticky substance that collects around and ...

  2. High-content neurite development study using optically patterned substrates.

    Directory of Open Access Journals (Sweden)

    Jonathan M Bélisle

    Full Text Available The study of neurite guidance in vitro relies on the ability to reproduce the distribution of attractive and repulsive guidance molecules normally expressed in vivo. The identification of subtle variations in the neurite response to changes in the spatial distribution of extracellular molecules can be achieved by monitoring the behavior of cells on protein gradients. To do this, automated high-content screening assays are needed to quantify the morphological changes resulting from growth on gradients of guidance molecules. Here, we present the use of laser-assisted protein adsorption by photobleaching (LAPAP to allow the fabrication of large-scale substrate-bound laminin-1 gradients to study neurite extension. We produced thousands of gradients of different slopes and analyzed the variations in neurite attraction of neuron-like cells (RGC-5. An image analysis algorithm processed bright field microscopy images, detecting each cell and quantifying the soma centroid and the initiation, terminal and turning angles of the longest neurite.

  3. Revisiting Randall's plaque

    African Journals Online (AJOL)

    N. Abrol

    Abstract. Kidney stones have probably affected mankind for ages with early reports in an Egyptian mummy. While prevalence of stone disease is increasing, its pathogenesis remains elusive. Randall, after his study on more than 1100 cadaver kidneys, gave hypothesis of subepithelial plaque acting as a nucleation site for ...

  4. EAMJ March- Plaque

    African Journals Online (AJOL)

    iMac User

    2008-03-01

    Mar 1, 2008 ... 3 March 2008. PLAQUE AND GROWTH CHARACTERISTICS OF DIFFERENT POLIOVIRUSES ISOLATED FROM ACUTE FLACCID. PARALYSIS IN NORTHERN NIGERIA. W. F. Sule, DVM, MSc, Lecturer, O. I. Oyedele, PhD, ..... John, T.J., Vaccine-associated paralytic polio in India. Bull. WHO. 2002; 80: 917.

  5. DECT evaluation of noncalcified coronary artery plaque

    Energy Technology Data Exchange (ETDEWEB)

    Ravanfar Haghighi, Rezvan [Medical Imaging Research Center and Colorectal Research Center, Shiraz University of Medical Science, Shiraz 719 363 5899 (Iran, Islamic Republic of); Chatterjee, S. [BGVS Chemical Engineering Building (Old), Indian Institute of Science, Bangalore 560012 (India); Tabin, Milo; Singh, Rishi P.; Sharma, Munish; Krishna, Karthik [Department of Forensic Medicine, All India Institute of Medical Sciences, New Delhi 110029 (India); Sharma, Sanjiv; Jagia, Priya [Department of Cardiac-Radiology, All India Institute of Medical Sciences, New Delhi 110029 (India); Ray, Ruma; Arava, Sudhir [Department of Pathology, All India Institute of Medical Sciences, New Delhi 110029 (India); Yadav, Rakesh [Department of Cardiology, All India Institute of Medical Sciences, New Delhi 110029 (India); Vani, V. C. [Department of Instrumentation and Applied Physics, Indian Institute of Science, Bangalore 560012 (India); Lakshmi, R.; Kumar, Pratik, E-mail: drpratikkumar@gmail.com [Department of Cardiac-Biochemistry, All India Institute of Medical Sciences, New Delhi 110029 (India); Mandal, Susama R. [Department of Medical Physics Unit IRCH, All India Institute of Medical Sciences, New Delhi 110029 (India)

    2015-10-15

    Purpose: Composition of the coronary artery plaque is known to have critical role in heart attack. While calcified plaque can easily be diagnosed by conventional CT, it fails to distinguish between fibrous and lipid rich plaques. In the present paper, the authors discuss the experimental techniques and obtain a numerical algorithm by which the electron density (ρ{sub e}) and the effective atomic number (Z{sub eff}) can be obtained from the dual energy computed tomography (DECT) data. The idea is to use this inversion method to characterize and distinguish between the lipid and fibrous coronary artery plaques. Methods: For the purpose of calibration of the CT machine, the authors prepare aqueous samples whose calculated values of (ρ{sub e}, Z{sub eff}) lie in the range of (2.65 × 10{sup 23} ≤ ρ{sub e} ≤ 3.64 × 10{sup 23}/cm{sup 3}) and (6.80 ≤ Z{sub eff} ≤ 8.90). The authors fill the phantom with these known samples and experimentally determine HU(V{sub 1}) and HU(V{sub 2}), with V{sub 1},V{sub 2} = 100 and 140 kVp, for the same pixels and thus determine the coefficients of inversion that allow us to determine (ρ{sub e}, Z{sub eff}) from the DECT data. The HU(100) and HU(140) for the coronary artery plaque are obtained by filling the channel of the coronary artery with a viscous solution of methyl cellulose in water, containing 2% contrast. These (ρ{sub e}, Z{sub eff}) values of the coronary artery plaque are used for their characterization on the basis of theoretical models of atomic compositions of the plaque materials. These results are compared with histopathological report. Results: The authors find that the calibration gives ρ{sub e} with an accuracy of ±3.5% while Z{sub eff} is found within ±1% of the actual value, the confidence being 95%. The HU(100) and HU(140) are found to be considerably different for the same plaque at the same position and there is a linear trend between these two HU values. It is noted that pure lipid type plaques

  6. Shoc2/Sur8 protein regulates neurite outgrowth.

    Directory of Open Access Journals (Sweden)

    Gonzalo Leon

    Full Text Available The Shoc2 protein has been implicated in the positive regulation of the Ras-ERK pathway by increasing the functional binding interaction between Ras and Raf, leading to increased ERK activity. Here we found that Shoc2 overexpression induced sustained ERK phosphorylation, notably in the case of EGF stimulation, and Shoc2 knockdown inhibited ERK activation. We demonstrate that ectopic overexpression of human Shoc2 in PC12 cells significantly promotes neurite extension in the presence of EGF, a stimulus that induces proliferation rather than differentiation in these cells. Finally, Shoc2 depletion reduces both NGF-induced neurite outgrowth and ERK activation in PC12 cells. Our data indicate that Shoc2 is essential to modulate the Ras-ERK signaling outcome in cell differentiation processes involved in neurite outgrowth.

  7. Fine Needle Aspiration Cytology in Diagnosis of Pure Neuritic Leprosy

    Directory of Open Access Journals (Sweden)

    Bipin Kumar

    2011-01-01

    Full Text Available Leprosy is a chronic infection affecting mainly the skin and peripheral nerve. Pure neuritic form of this disease manifests by involvement of the nerve in the absence of skin lesions. Therefore, it can sometimes create a diagnostic problem. It often requires a nerve biopsy for diagnosis, which is an invasive procedure and may lead to neural deficit. Fine needle aspiration cytology (FNAC of an affected nerve can be a valuable and less invasive procedure for the diagnosis of such cases. We report five suspected cases of pure neuritic Hansen's disease involving the common and superficial peroneal, ulnar, and median nerve, who underwent FNAC. Smears revealed nerve fibers infiltrated by chronic inflammatory cells in all cases, presence of epithelioid cells granulomas, and Langhans giant cells in three cases, and acid fast bacilli in two cases. In conclusion, FNAC is a safe, less invasive, and time saving procedure for the diagnosis of pure neuritic leprosy.

  8. Fine Needle Aspiration Cytology in Diagnosis of Pure Neuritic Leprosy

    Science.gov (United States)

    Kumar, Bipin; Pradhan, Anju

    2011-01-01

    Leprosy is a chronic infection affecting mainly the skin and peripheral nerve. Pure neuritic form of this disease manifests by involvement of the nerve in the absence of skin lesions. Therefore, it can sometimes create a diagnostic problem. It often requires a nerve biopsy for diagnosis, which is an invasive procedure and may lead to neural deficit. Fine needle aspiration cytology (FNAC) of an affected nerve can be a valuable and less invasive procedure for the diagnosis of such cases. We report five suspected cases of pure neuritic Hansen's disease involving the common and superficial peroneal, ulnar, and median nerve, who underwent FNAC. Smears revealed nerve fibers infiltrated by chronic inflammatory cells in all cases, presence of epithelioid cells granulomas, and Langhans giant cells in three cases, and acid fast bacilli in two cases. In conclusion, FNAC is a safe, less invasive, and time saving procedure for the diagnosis of pure neuritic leprosy. PMID:21660285

  9. Neuroprotective copper bis(thiosemicarbazonato complexes promote neurite elongation.

    Directory of Open Access Journals (Sweden)

    Laura Bica

    Full Text Available Abnormal biometal homeostasis is a central feature of many neurodegenerative disorders including Alzheimer's disease (AD, Parkinson's disease (PD, and motor neuron disease. Recent studies have shown that metal complexing compounds behaving as ionophores such as clioquinol and PBT2 have robust therapeutic activity in animal models of neurodegenerative disease; however, the mechanism of neuroprotective action remains unclear. These neuroprotective or neurogenerative processes may be related to the delivery or redistribution of biometals, such as copper and zinc, by metal ionophores. To investigate this further, we examined the effect of the bis(thiosemicarbazonato-copper complex, Cu(II(gtsm on neuritogenesis and neurite elongation (neurogenerative outcomes in PC12 neuronal-related cultures. We found that Cu(II(gtsm induced robust neurite elongation in PC12 cells when delivered at concentrations of 25 or 50 nM overnight. Analogous effects were observed with an alternative copper bis(thiosemicarbazonato complex, Cu(II(atsm, but at a higher concentration. Induction of neurite elongation by Cu(II(gtsm was restricted to neurites within the length range of 75-99 µm with a 2.3-fold increase in numbers of neurites in this length range with 50 nM Cu(II(gtsm treatment. The mechanism of neurogenerative action was investigated and revealed that Cu(II(gtsm inhibited cellular phosphatase activity. Treatment of cultures with 5 nM FK506 (calcineurin phosphatase inhibitor resulted in analogous elongation of neurites compared to 50 nM Cu(II(gtsm, suggesting a potential link between Cu(II(gtsm-mediated phosphatase inhibition and neurogenerative outcomes.

  10. Atherosclerotic plaque rupture: local or systemic process?

    NARCIS (Netherlands)

    Lutgens, Esther; van Suylen, Robert-Jan; Faber, Birgit C.; Gijbels, Marion J.; Eurlings, Petra M.; Bijnens, Ann-Pascale; Cleutjens, Kitty B.; Heeneman, Sylvia; Daemen, Mat J. A. P.

    2003-01-01

    It is generally established that the unstable plaque is the major cause of acute clinical sequelae of atherosclerosis. Unfortunately, terms indicating lesions prone to plaque instability, such as "vulnerable plaque," and the different phenotypes of unstable plaques, such as plaque rupture, plaque

  11. Glial membranes at the node of Ranvier prevent neurite outgrowth

    DEFF Research Database (Denmark)

    Huang, Jeffrey K; Phillips, Greg R; Roth, Alejandro D

    2005-01-01

    Nodes of Ranvier are regularly placed, nonmyelinated axon segments along myelinated nerves. Here we show that nodal membranes isolated from the central nervous system (CNS) of mammals restricted neurite outgrowth of cultured neurons. Proteomic analysis of these membranes revealed several inhibitors...... of neurite outgrowth, including the oligodendrocyte myelin glycoprotein (OMgp). In rat spinal cord, OMgp was not localized to compact myelin, as previously thought, but to oligodendroglia-like cells, whose processes converge to form a ring that completely encircles the nodes. In OMgp-null mice, CNS nodes...

  12. Psoriasis (chronic plaque).

    Science.gov (United States)

    Naldi, Luigi; Rzany, Berthold

    2009-01-09

    Psoriasis affects 1-3% of the population, in some people causing changes to the nails and joints in addition to skin lesions. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of systemic drug treatments, topical drug treatments, and non-drug treatments (other than ultraviolet light) for chronic plaque psoriasis? What are the effects of ultraviolet light treatments for chronic plaque psoriasis? What are the effects of combined treatment with drugs plus ultraviolet light on chronic plaque psoriasis? What are the effects of combined systemic plus topical drug treatments for chronic plaque psoriasis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2007 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found 122 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review we present information relating to the effectiveness and safety of the following interventions: acupuncture, adding calcipotriol (topical) to psoralen plus ultraviolet light A or ultraviolet light B, adding oral retinoids to psoralen plus ultraviolet A (PUVA), alefacept, balneotherapy, ciclosporin, dithranol, T cell-targeted therapies, cytokine blocking agents, emollients (alone or plus ultraviolet light B), etanercept, fish oil supplementation, fumaric acid derivatives, Goeckerman treatment, heliotherapy, infliximab, Ingram regimen, keratolytics (salicylic acid, urea), leflunomide, methotrexate, oral pimecrolimus, phototherapy plus balneotherapy, psoralen plus ultraviolet A, psychotherapy, oral retinoids (alone or with

  13. The effects of hematopoietic growth factors on neurite outgrowth.

    Science.gov (United States)

    Su, Ye; Cui, Lili; Piao, Chunshu; Li, Bin; Zhao, Li-Ru

    2013-01-01

    Stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) are initially discovered as the essential hematopoietic growth factors regulating bone marrow stem cell proliferation and differentiation, and SCF in combination with G-CSF (SCF+G-CSF) has synergistic effects on bone marrow stem cell mobilization. In this study we have determined the effect of SCF and G-CSF on neurite outgrowth in rat cortical neurons. Using molecular and cellular biology and live cell imaging approaches, we have revealed that receptors for SCF and G-CSF are expressed on the growth core of cortical neurons, and that SCF+G-CSF synergistically enhances neurite extension through PI3K/AKT and NFκB signaling pathways. Moreover, SCF+G-CSF induces much greater NFκB activation, NFκB transcriptional binding and brain-derived neurotrophic factor (BDNF) production than SCF or G-CSF alone. In addition, we have also observed that BDNF, the target gene of NFκB, is required for SCF+G-CSF-induced neurite outgrowth. These data suggest that SCF+G-CSF has synergistic effects to promote neurite growth. This study provides new insights into the contribution of hematopoietic growth factors in neuronal plasticity.

  14. The effects of hematopoietic growth factors on neurite outgrowth.

    Directory of Open Access Journals (Sweden)

    Ye Su

    Full Text Available Stem cell factor (SCF and granulocyte colony-stimulating factor (G-CSF are initially discovered as the essential hematopoietic growth factors regulating bone marrow stem cell proliferation and differentiation, and SCF in combination with G-CSF (SCF+G-CSF has synergistic effects on bone marrow stem cell mobilization. In this study we have determined the effect of SCF and G-CSF on neurite outgrowth in rat cortical neurons. Using molecular and cellular biology and live cell imaging approaches, we have revealed that receptors for SCF and G-CSF are expressed on the growth core of cortical neurons, and that SCF+G-CSF synergistically enhances neurite extension through PI3K/AKT and NFκB signaling pathways. Moreover, SCF+G-CSF induces much greater NFκB activation, NFκB transcriptional binding and brain-derived neurotrophic factor (BDNF production than SCF or G-CSF alone. In addition, we have also observed that BDNF, the target gene of NFκB, is required for SCF+G-CSF-induced neurite outgrowth. These data suggest that SCF+G-CSF has synergistic effects to promote neurite growth. This study provides new insights into the contribution of hematopoietic growth factors in neuronal plasticity.

  15. Discovery of pyrroloimidazoles as agents stimulating neurite outgrowth

    NARCIS (Netherlands)

    Beck, Barbara; Leppert, Christian A.; Mueller, Bernhard K.; Dömling, Alexander

    2006-01-01

    A diverse library of substituted pyrroloimidazoles was assembled by a multicomponent reaction (MCR) of tosylmethyl isocyanides (TOSMIC), indole carbaldehydes and primary amines in a van Leusen reaction. A library of this scaffold was screened in a phenotypic assay for neurite outgrowth. Several

  16. The Deacetylase HDAC6 Mediates Endogenous Neuritic Tau Pathology

    Directory of Open Access Journals (Sweden)

    Jui-Heng Tseng

    2017-08-01

    Full Text Available The initiating events that promote tau mislocalization and pathology in Alzheimer’s disease (AD are not well defined, partly because of the lack of endogenous models that recapitulate tau dysfunction. We exposed wild-type neurons to a neuroinflammatory trigger and examined the effect on endogenous tau. We found that tau re-localized and accumulated within pathological neuritic foci, or beads, comprised of mostly hypo-phosphorylated, acetylated, and oligomeric tau. These structures were detected in aged wild-type mice and were enhanced in response to neuroinflammation in vivo, highlighting a previously undescribed endogenous age-related tau pathology. Strikingly, deletion or inhibition of the cytoplasmic shuttling factor HDAC6 suppressed neuritic tau bead formation in neurons and mice. Using mass spectrometry-based profiling, we identified a single neuroinflammatory factor, the metalloproteinase MMP-9, as a mediator of neuritic tau beading. Thus, our study uncovers a link between neuroinflammation and neuritic tau beading as a potential early-stage pathogenic mechanism in AD.

  17. TERAHERTZ RADIATION INFLUENCE ON THE GROWING OF NEURITES

    Directory of Open Access Journals (Sweden)

    M. V. Tsurkan

    2013-01-01

    Full Text Available Our research was devoted to the impact of broadband pulsed THz radiation in the frequency range of 0.05 to 2 THz on the neurite growth in the sensory ganglia of 10-12-day chicken embryos. Dependence of changes in functional responses of cells on the average output power has been found.

  18. Brain Tissue Compartment Density Estimated Using Diffusion-Weighted MRI Yields Tissue Parameters Consistent With Histology

    OpenAIRE

    Sepehrband, Farshid; Clark, Kristi A.; Ullmann, Jeremy F. P.; Kurniawan, Nyoman D; Leanage, Gayeshika; Reutens, David C.; Yang, Zhengyi

    2015-01-01

    We examined whether quantitative density measures of cerebral tissue consistent with histology can be obtained from diffusion magnetic resonance imaging (MRI). By incorporating prior knowledge of myelin and cell membrane densities, absolute tissue density values were estimated from relative intra-cellular and intra-neurite density values obtained from diffusion MRI. The NODDI (neurite orientation distribution and density imaging) technique, which can be applied clinically, was used. Myelin de...

  19. Atherosclerotic plaque delamination: Experiments and 2D finite element model to simulate plaque peeling in two strains of transgenic mice.

    Science.gov (United States)

    Merei, Bilal; Badel, Pierre; Davis, Lindsey; Sutton, Michael A; Avril, Stéphane; Lessner, Susan M

    2017-03-01

    Finite element analyses using cohesive zone models (CZM) can be used to predict the fracture of atherosclerotic plaques but this requires setting appropriate values of the model parameters. In this study, material parameters of a CZM were identified for the first time on two groups of mice (ApoE(-/-) and ApoE(-/-) Col8(-/-)) using the measured force-displacement curves acquired during delamination tests. To this end, a 2D finite-element model of each plaque was solved using an explicit integration scheme. Each constituent of the plaque was modeled with a neo-Hookean strain energy density function and a CZM was used for the interface. The model parameters were calibrated by minimizing the quadratic deviation between the experimental force displacement curves and the model predictions. The elastic parameter of the plaque and the CZM interfacial parameter were successfully identified for a cohort of 11 mice. The results revealed that only the elastic parameter was significantly different between the two groups, ApoE(-/-) Col8(-/-) plaques being less stiff than ApoE(-/-) plaques. Finally, this study demonstrated that a simple 2D finite element model with cohesive elements can reproduce fairly well the plaque peeling global response. Future work will focus on understanding the main biological determinants of regional and inter-individual variations of the material parameters used in the model. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Inhibitory Activity of Yokukansankachimpihange against Nerve Growth Factor-Induced Neurite Growth in Cultured Rat Dorsal Root Ganglion Neurons

    Directory of Open Access Journals (Sweden)

    Chiaki Murayama

    2015-08-01

    Full Text Available Chronic pruritus is a major and distressing symptom of many cutaneous diseases, however, the treatment remains a challenge in the clinic. The traditional Chinese-Japanese medicine (Kampo medicine is a conservative and increasingly popular approach to treat chronic pruritus for both patients and medical providers. Yokukansankachimpihange (YKH, a Kampo formula has been demonstrated to be effective in the treatment of itching of atopic dermatitis in Japan although its pharmacological mechanism is unknown clearly. In an attempt to clarify its pharmacological actions, in this study, we focused on the inhibitory activity of YKH against neurite growth induced with nerve growth factor (NGF in cultured rat dorsal root ganglion (DRG neurons because epidermal hyperinnervation is deeply related to itch sensitization. YKH showed approximately 200-fold inhibitory activity against NGF-induced neurite growth than that of neurotropin (positive control, a drug used clinically for treatment of chronic pruritus. Moreover, it also found that Uncaria hook, Bupleurum root and their chemical constituents rhynchophylline, hirsutine, and saikosaponin a, d showed inhibitory activities against NGF-induced neurite growth, suggesting they should mainly contribute to the inhibitory activity of YKH. Further study on the effects of YKH against epidermal nerve density in “itch-scratch” animal models is under investigation.

  1. Neurite outgrowth in human iPSC-derived neurons

    Science.gov (United States)

    Data on morphology of rat and human neurons in cell cultureThis dataset is associated with the following publication:Druwe, I., T. Freudenrich , K. Wallace , T. Shafer , and W. Mundy. Comparison of Human Induced PluripotentStem Cell-Derived Neurons and Rat Primary CorticalNeurons as In Vitro Models of Neurite Outgrowth. Applied In vitro Toxicology. Mary Ann Liebert, Inc., Larchmont, NY, USA, 2(1): 26-36, (2016).

  2. GIT1 enhances neurite outgrowth by stimulating microtubule assembly

    Directory of Open Access Journals (Sweden)

    Yi-sheng Li

    2016-01-01

    Full Text Available GIT1, a G-protein-coupled receptor kinase interacting protein, has been reported to be involved in neurite outgrowth. However, the neurobiological functions of the protein remain unclear. In this study, we found that GIT1 was highly expressed in the nervous system, and its expression was maintained throughout all stages of neuritogenesis in the brain. In primary cultured mouse hippocampal neurons from GIT1 knockout mice, there was a significant reduction in total neurite length per neuron, as well as in the average length of axon-like structures, which could not be prevented by nerve growth factor treatment. Overexpression of GIT1 significantly promoted axon growth and fully rescued the axon outgrowth defect in the primary hippocampal neuron cultures from GIT1 knockout mice. The GIT1 N terminal region, including the ADP ribosylation factor-GTPase activating protein domain, the ankyrin domains and the Spa2 homology domain, were sufficient to enhance axonal extension. Importantly, GIT1 bound to many tubulin proteins and microtubule-associated proteins, and it accelerated microtubule assembly in vitro. Collectively, our findings suggest that GIT1 promotes neurite outgrowth, at least partially by stimulating microtubule assembly. This study provides new insight into the cellular and molecular pathogenesis of GIT1-associated neurological diseases.

  3. Neurite outgrowth on fluorinated polyimide film micropatterned by ion irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Okuyama, Y.; Sato, M.; Nagaoka, S.; Kawakami, H. E-mail: kawakami-hiroyoshi@c.metro-u.ac.jp; Suzuki, Y.; Iwaki, M

    2003-05-01

    In this study, we investigated neurite outgrowth on a fluorinated polyimide film micropatterned by ion irradiation. We used the fluorinated polyimide because of its excellent thermal and mechanical properties and biocompatibility. Rattus norvegicus chromaphin (PC12) cells were used for in vitro studies. The polyimide films were irradiated with He{sup +}, Ne{sup +} or Kr{sup +} at 1 x 10{sup 14} ions/cm{sup 2} using an ion-beam mask. The lines in the mask were 120 and 160 {mu}m wide and 120-160 {mu}m apart. PC12 cells were selectively adhered on the polyimide film micropatterned by Kr{sup +}-irradiation. However, the neurite length on the film irradiated by Kr{sup +} was shorter than that determined in the film irradiated by He{sup +}. On the other hand, neurite outgrowth on the polyimide film micropatterned by He{sup +}-irradiation was at least 100 {mu}m in length. This initial study indicated the enhanced outgrowth of PC12 cells on the fluorinated polyimide film micropatterned by ion irradiation.

  4. Stimulation of neuronal neurite outgrowth using functionalized carbon nanotubes

    Science.gov (United States)

    Matsumoto, K.; Sato, C.; Naka, Y.; Whitby, R.; Shimizu, N.

    2010-03-01

    Low concentrations (0.11-1.7 µg ml - 1) of functionalized carbon nanotubes (CNTs), which are multi-walled CNTs modified by amino groups, when added with nerve growth factor (NGF), promoted outgrowth of neuronal neurites in dorsal root ganglion (DRG) neurons and rat pheochromocytoma cell line PC12h cells in culture media. The quantity of active extracellular signal-regulated kinase (ERK) was higher after the addition of both 0.85 µg ml - 1 CNTs and NGF than that with NGF alone. CNTs increased the number of cells with neurite outgrowth in DRG neurons and PC12h cells after the inhibition of the ERK signaling pathway using a mitogen-activated protein kinase (MAPK)/ERK kinase (MEK) inhibitor. Active ERK proteins were detected in MEK inhibitor-treated neurons after the addition of CNTs to the culture medium. These results demonstrate that CNTs may stimulate neurite outgrowth by activation of the ERK signaling pathway. Thus, CNTs are biocompatible and are promising candidates for biological applications and devices.

  5. Plaques of Alzheimer's disease originate from cysts of Borrelia burgdorferi, the Lyme disease spirochete.

    Science.gov (United States)

    MacDonald, Alan B

    2006-01-01

    Here is hypothesized a truly revolutionary notion that rounded cystic forms of Borrelia burgdorferi are the root cause of the rounded structures called plaques in the Alzheimer brain. Rounded "plaques' in high density in brain tissue are emblematic of Alzheimer's disease (AD). Plaques may be conceptualized as rounded "pock mark-like" areas of brain tissue injury. In this century, in brain tissue of AD, plaques are Amyloid Plaques according to the most up to date textbooks. In the last century, however, Dr. Alois Alzheimer did not require amyloid as the pathogenesis for either the disease or for the origin of its plaques. Surely, amyloid is an event in AD, but it may not be the primal cause of AD. Indeed in plaques, amyloid is regularly represented by the "congophilic core" structure which is so named because the waxy amyloid material binds the congo red stain and is congophilic. However an accepted subset of plaques in AD is devoid of a congophilic amyloid core region (these plaques "cotton wool" type plaques, lack a central congophilic core structure). Furthermore, there is "plaque diversity" in Alzheimer's; small, medium and large plaques parallel variable cystic diameters for Borrelia burgdorferi. Perturbations of AD plaque structure (i.e. young plaques devoid of a central core and older plaques with or without a central core structure) offer room for an alternate pathway for explanation of ontogeny of the plaque structures. If amyloid is not required to initiate all of the possible plaques in Alzheimer's, is it possible that amyloid just a by product of a more fundamental primal path to dementia? If a byproduct status is assigned to amyloid in the realm of plaque formation, then is amyloid also an epiphenomenon rather than a primary pathogenesis for Alzheimer's disease. In the "anatomy is destiny" model, cysts of borrelia are always round. Why then not accept roundness as a fundamental "structure determines function" argument for the answer to the mystery of

  6. Neural cell adhesion molecule 2 promotes the formation of filopodia and neurite branching by inducing submembrane increases in Ca2+ levels.

    Science.gov (United States)

    Sheng, Lifu; Leshchyns'ka, Iryna; Sytnyk, Vladimir

    2015-01-28

    Changes in expression of the neural cell adhesion molecule 2 (NCAM2) have been proposed to contribute to neurodevelopmental disorders in humans. The role of NCAM2 in neuronal differentiation remains, however, poorly understood. Using genetically encoded Ca(2+) reporters, we show that clustering of NCAM2 at the cell surface of mouse cortical neurons induces submembrane [Ca(2+)] spikes, which depend on the L-type voltage-dependent Ca(2+) channels (VDCCs) and require activation of the protein tyrosine kinase c-Src. We also demonstrate that clustering of NCAM2 induces L-type VDCC- and c-Src-dependent activation of CaMKII. NCAM2-dependent submembrane [Ca(2+)] spikes colocalize with the bases of filopodia. NCAM2 activation increases the density of filopodia along neurites and neurite branching and outgrowth in an L-type VDCC-, c-Src-, and CaMKII-dependent manner. Our results therefore indicate that NCAM2 promotes the formation of filopodia and neurite branching by inducing Ca(2+) influx and CaMKII activation. Changes in NCAM2 expression in Down syndrome and autistic patients may therefore contribute to abnormal neurite branching observed in these disorders. Copyright © 2015 the authors 0270-6474/15/351739-14$15.00/0.

  7. Large-scale analysis of neurite growth dynamics on micropatterned substrates

    OpenAIRE

    Wissner-Gross, Zachary D.; Scott, Mark Andrew; Ku, David L.; Ramaswamy, Priya

    2010-01-01

    During both development and regeneration of the nervous system, neurons display complex growth dynamics, and several neurites compete to become the neuron's single axon. Numerous mathematical and biophysical models have been proposed to explain this competition, which remain experimentally unverified. Large-scale, precise, and repeatable measurements of neurite dynamics have been difficult to perform, since neurons have varying numbers of neurites, which themselves have complex morphologies. ...

  8. HDL-mimetic PLGA nanoparticle to target atherosclerosis plaque macrophages

    NARCIS (Netherlands)

    Sanchez-Gaytan, Brenda L.; Fay, Francois; Lobatto, Mark E.; Tang, Jun; Ouimet, Mireille; Kim, Yongtae; van der Staay, Susanne E. M.; van Rijs, Sarian M.; Priem, Bram; Zhang, Liangfang; Fisher, Edward A.; Moore, Kathryn J.; Langer, Robert; Fayad, Zahi A.; Mulder, Willem J. M.

    2015-01-01

    High-density lipoprotein (HDL) is a natural nanoparticle that exhibits an intrinsic affinity for atherosclerotic plaque macrophages. Its natural targeting capability as well as the option to incorporate lipophilic payloads, e.g., imaging or therapeutic components, in both the hydrophobic core and

  9. Stimulation of Neurite Outgrowth Using an Electrically Conducting Polymer

    Science.gov (United States)

    Schmidt, Christine E.; Shastri, Venkatram R.; Vacanti, Joseph P.; Langer, Robert

    1997-08-01

    Damage to peripheral nerves often cannot be repaired by the juxtaposition of the severed nerve ends. Surgeons have typically used autologous nerve grafts, which have several drawbacks including the need for multiple surgical procedures and loss of function at the donor site. As an alternative, the use of nerve guidance channels to bridge the gap between severed nerve ends is being explored. In this paper, the electrically conductive polymer--oxidized polypyrrole (PP)--has been evaluated for use as a substrate to enhance nerve cell interactions in culture as a first step toward potentially using such polymers to stimulate in vivo nerve regeneration. Image analysis demonstrates that PC-12 cells and primary chicken sciatic nerve explants attached and extended neurites equally well on both PP films and tissue culture polystyrene in the absence of electrical stimulation. In contrast, PC-12 cells interacted poorly with indium tin oxide (ITO), poly(L-lactic acid) (PLA), and poly(lactic acid-coglycolic acid) surfaces. However, PC-12 cells cultured on PP films and subjected to an electrical stimulus through the film showed a significant increase in neurite lengths compared with ones that were not subjected to electrical stimulation through the film and tissue culture polystyrene controls. The median neurite length for PC-12 cells grown on PP and subjected to an electrical stimulus was 18.14 μ m (n = 5643) compared with 9.5 μ m (n = 4440) for controls. Furthermore, animal implantation studies reveal that PP invokes little adverse tissue response compared with poly(lactic acid-coglycolic acid).

  10. Intraplaque Hemorrhage and the Plaque Surface in Carotid Atherosclerosis: The Plaque At RISK Study (PARISK)

    NARCIS (Netherlands)

    van Dijk, A. C.; Truijman, M. T. B.; Hussain, B.; Zadi, T.; Saiedie, G.; de Rotte, A. A. J.; Liem, M. I.; van der Steen, A. F. W.; Daemen, M. J. A. P.; Koudstaal, P. J.; Nederkoorn, P. J.; Hendrikse, J.; Kooi, M. E.; van der Lugt, A.

    2015-01-01

    An important characteristic of vulnerable plaque, intraplaque hemorrhage, may predict plaque rupture. Plaque rupture can be visible on noninvasive imaging as a disruption of the plaque surface. We investigated the association between intraplaque hemorrhage and disruption of the plaque surface. We

  11. Toothbrush efficacy for plaque removal.

    Science.gov (United States)

    Nightingale, K J; Chinta, S K; Agarwal, P; Nemelivsky, M; Frisina, A C; Cao, Z; Norman, R G; Fisch, G S; Corby, P

    2014-11-01

    To determine the effectiveness of a novel sonic toothbrush in reducing plaque and in maintenance of gingival health when compared to a standard manual brush. This study was a block-randomized, examiner-blind, two-treatment, parallel group, single centre clinical investigation. A total of 84 subjects were enrolled and randomly assigned to receive either the Panasonic EW-DL90 or an American Dental Association-endorsed manual toothbrush. Subjects were instructed to follow a twice-daily brushing regimen without flossing. Plaque levels and gingival health were assessed at baseline and after 1 and 3 weeks of treatment using the Turesky Modification of the Quigley-Hein Plaque Index and the Papillary Bleeding Score. Subjects assigned to the EW-DL90 group had significantly lower plaque levels after 1 and 3 weeks of treatment than those in the manual group (P = 0.003 and 0.0035, respectively). Both groups showed a reduction in plaque levels at Week 3 relative to baseline. The EW-DL90 group had significantly lower gingival inflammation scores after 1 week of treatment (P = 0.0293), but there was no difference between groups after 3 weeks of treatment. The EW-DL90 toothbrush safely and effectively removes more plaque than a standard manual toothbrush. Improvement in gingival inflammation was observed after 1 week of treatment. There was no difference in Papillary Bleeding Score between the two groups after 3 weeks of treatment. The newly developed sonic brush (Panasonic EW-DL90) tested in this study was found to be more effective than a manual toothbrush at plaque removal. The papillary bleeding scores were significantly lower in the sonic brush group after 1 week of product use. After 3 weeks of product use, both treatment groups had similar papillary bleeding scores almost returning to baseline values. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Cloning of a Gene Whose Expression is Increased in Scrapie and in Senile Plaques in Human Brain

    Science.gov (United States)

    Wietgrefe, S.; Zupancic, M.; Haase, A.; Chesebro, B.; Race, R.; Frey, W.; Rustan, T.; Friedman, R. L.

    1985-12-01

    A complementary DNA library was constructed from messenger RNA's extracted from the brains of mice infected with the scrapie agent. The library was differentially screened with the objectives of finding clones that might be used as markers of infection and finding clones of genes whose increased expression might be correlated with the pathological changes common to scrapie and Alzheimer's disease. A gene was identified whose expression is increased in scrapie. The complementary DNA corresponding to this gene hybridized preferentially and focally to cells in the brains of scrapie-infected animals. The cloned DNA also hybridized to the neuritic plaques found with increased frequency in brains of patients with Alzheimer's disease.

  13. Denitrification in human dental plaque

    Directory of Open Access Journals (Sweden)

    Verstraete Willy

    2010-03-01

    Full Text Available Abstract Background Microbial denitrification is not considered important in human-associated microbial communities. Accordingly, metabolic investigations of the microbial biofilm communities of human dental plaque have focused on aerobic respiration and acid fermentation of carbohydrates, even though it is known that the oral habitat is constantly exposed to nitrate (NO3- concentrations in the millimolar range and that dental plaque houses bacteria that can reduce this NO3- to nitrite (NO2-. Results We show that dental plaque mediates denitrification of NO3- to nitric oxide (NO, nitrous oxide (N2O, and dinitrogen (N2 using microsensor measurements, 15N isotopic labelling and molecular detection of denitrification genes. In vivo N2O accumulation rates in the mouth depended on the presence of dental plaque and on salivary NO3- concentrations. NO and N2O production by denitrification occurred under aerobic conditions and was regulated by plaque pH. Conclusions Increases of NO concentrations were in the range of effective concentrations for NO signalling to human host cells and, thus, may locally affect blood flow, signalling between nerves and inflammatory processes in the gum. This is specifically significant for the understanding of periodontal diseases, where NO has been shown to play a key role, but where gingival cells are believed to be the only source of NO. More generally, this study establishes denitrification by human-associated microbial communities as a significant metabolic pathway which, due to concurrent NO formation, provides a basis for symbiotic interactions.

  14. ADF/cofilin-mediated actin retrograde flow directs neurite formation in the developing brain.

    Science.gov (United States)

    Flynn, Kevin C; Hellal, Farida; Neukirchen, Dorothee; Jacob, Sonja; Tahirovic, Sabina; Dupraz, Sebastian; Stern, Sina; Garvalov, Boyan K; Gurniak, Christine; Shaw, Alisa E; Meyn, Liane; Wedlich-Söldner, Roland; Bamburg, James R; Small, J Victor; Witke, Walter; Bradke, Frank

    2012-12-20

    Neurites are the characteristic structural element of neurons that will initiate brain connectivity and elaborate information. Early in development, neurons are spherical cells but this symmetry is broken through the initial formation of neurites. This fundamental step is thought to rely on actin and microtubule dynamics. However, it is unclear which aspects of the complex actin behavior control neuritogenesis and which molecular mechanisms are involved. Here, we demonstrate that augmented actin retrograde flow and protrusion dynamics facilitate neurite formation. Our data indicate that a single family of actin regulatory proteins, ADF/Cofilin, provides the required control of actin retrograde flow and dynamics to form neurites. In particular, the F-actin severing activity of ADF/Cofilin organizes space for the protrusion and bundling of microtubules, the backbone of neurites. Our data reveal how ADF/Cofilin organizes the cytoskeleton to drive actin retrograde flow and thus break the spherical shape of neurons. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Growth, collapse, and stalling in a mechanical model for neurite motility

    CERN Document Server

    Recho, Pierre; Goriely, Alain

    2015-01-01

    Neurites, the long cellular protrusions that form the routes of the neuronal network are capable to actively extend during early morphogenesis or to regenerate after trauma. To perform this task, they rely on their cytoskeleton for mechanical support. In this paper, we present a three-component active gel model that describes neurites in the three robust mechanical states observed experimentally: collapsed, static, and motile. These states arise from an interplay between the physical forces driven by growth of the microtubule-rich inner core of the neurite and the acto-myosin contractility of its surrounding cortical membrane. In particular, static states appear as a mechanical traction/compression balance of these two parallel structures. The model predicts how the response of a neurite to a towing force depends on the force magnitude and recovers the response of neurites to several drug treatments that modulate the cytoskeleton active and passive properties.

  16. Mapping dynamic branch displacements: A versatile method to quantify spatiotemporal neurite dynamics

    Directory of Open Access Journals (Sweden)

    Masaki eHiramoto

    2011-09-01

    Full Text Available AbstractQuantification of the movement of axons and dendrites is essential to study circuit formation. Several methods have been developed to quantify the movement of neurites in simplified systems, however these quantification methods are specialized for a limited type of predicted movements in the particular assay systems. The movement of neurites in vivo includes many unexpected rearrangements. Establishment of a method that can detect and quantify a variety of patterning events will reveal novel phenomena in circuit formation and make it possible to conduct deeper investigation of the molecular and cellular bases of these events. Here we present a versatile method that represents a quantitative analysis of the integrated movement of neurites on a spatial map. We show that the method is useful to analyze several types of neurite behaviors, such as changes in the directionality of neurite movements, fasciculation of axons or changes in territories of dendritic fields.

  17. Angiogenesis in the atherosclerotic plaque

    Directory of Open Access Journals (Sweden)

    Caroline Camaré

    2017-08-01

    Full Text Available Atherosclerosis is a multifocal alteration of the vascular wall of medium and large arteries characterized by a local accumulation of cholesterol and non-resolving inflammation. Atherothrombotic complications are the leading cause of disability and mortality in western countries. Neovascularization in atherosclerotic lesions plays a major role in plaque growth and instability. The angiogenic process is mediated by classical angiogenic factors and by additional factors specific to atherosclerotic angiogenesis. In addition to its role in plaque progression, neovascularization may take part in plaque destabilization and thromboembolic events. Anti-angiogenic agents are effective to reduce atherosclerosis progression in various animal models. However, clinical trials with anti-angiogenic drugs, mainly anti-VEGF/VEGFR, used in anti-cancer therapy show cardiovascular adverse effects, and require additional investigations.

  18. Plaque control and oral hygiene methods

    LENUS (Irish Health Repository)

    Harrison, Peter

    2017-06-01

    The experimental gingivitis study of Löe et al.1 demonstrated a cause and effect relationship between plaque accumulation and gingival inflammation, and helped to establish plaque\\/biofilm as the primary risk factor for gingivitis. When healthy individuals withdrew oral hygiene efforts, gingival inflammation ensued within 21 days in all subjects. Once effective plaque removal was recommenced, clinical gingival health was quickly re-established – indicating that plaque-associated inflammation is modifiable by plaque control. As current consensus confirms that gingivitis and periodontitis may be viewed as a continuum of disease,2 the rationale for achieving effective plaque control is clear.

  19. Amyloid plaque formation precedes dendritic spine loss.

    Science.gov (United States)

    Bittner, Tobias; Burgold, Steffen; Dorostkar, Mario M; Fuhrmann, Martin; Wegenast-Braun, Bettina M; Schmidt, Boris; Kretzschmar, Hans; Herms, Jochen

    2012-12-01

    Amyloid-beta plaque deposition represents a major neuropathological hallmark of Alzheimer's disease. While numerous studies have described dendritic spine loss in proximity to plaques, much less is known about the kinetics of these processes. In particular, the question as to whether synapse loss precedes or follows plaque formation remains unanswered. To address this question, and to learn more about the underlying kinetics, we simultaneously imaged amyloid plaque deposition and dendritic spine loss by applying two-photon in vivo microscopy through a cranial window in double transgenic APPPS1 mice. As a result, we first observed that the rate of dendritic spine loss in proximity to plaques is the same in both young and aged animals. However, plaque size only increased significantly in the young cohort, indicating that spine loss persists even many months after initial plaque appearance. Tracking the fate of individual spines revealed that net spine loss is caused by increased spine elimination, with the rate of spine formation remaining constant. Imaging of dendritic spines before and during plaque formation demonstrated that spine loss around plaques commences at least 4 weeks after initial plaque formation. In conclusion, spine loss occurs, shortly but with a significant time delay, after the birth of new plaques, and persists in the vicinity of amyloid plaques over many months. These findings hence give further hope to the possibility that there is a therapeutic window between initial amyloid plaque deposition and the onset of structural damage at spines.

  20. Advances in Aβ plaque detection and the value of knowing: overcoming challenges to improving patient outcomes in Alzheimer's disease.

    Science.gov (United States)

    Jovalekic, Aleksandar; Bullich, Santiago; Catafau, Ana; de Santi, Susan

    2016-12-01

    Clinical diagnosis of Alzheimer's disease (AD) can be challenging as numerous diseases mimic the characteristics of AD. In this light, recent guidelines developed by different associations and working groups point out the need for biomarkers to support AD diagnosis. This paper discusses 18F-labeled radiotracers (which are indicated for PET imaging of the brain) and ongoing clinical studies that aim to generate new evidence for the usage of amyloid imaging. In addition to their relatively long half-life, these agents are known for their high sensitivity and high negative predictive values for detection of neuriticplaques. Comparisons with other biomarkers are provided and implications of diagnostic disclosures discussed. Finally, recent data from clinical trials underscore the importance of amyloid PET for detecting, quantifying and monitoring Aβ plaque deposits.

  1. Effect of 710 nm visible light irradiation on neurite outgrowth in primary rat cortical neurons following ischemic insult

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Dong-Hee [Center for Neuroscience Research, SMART Institute of Advanced Biomedical Science, Konkuk University, Seoul (Korea, Republic of); Department of Medical Science, Konkuk University School of Medicine, Seoul (Korea, Republic of); Lee, Kyoung-Hee; Kim, Ji-Hye; Kim, Moon Young [Center for Neuroscience Research, SMART Institute of Advanced Biomedical Science, Konkuk University, Seoul (Korea, Republic of); Lim, Jeong Hoon [Department of Rehabilitation Medicine, Konkuk University School of Medicine, Seoul (Korea, Republic of); Rehabilitation Medicine, Division of Neurology, Department of Medicine, National University Hospital, National University Health System (Singapore); Lee, Jongmin, E-mail: leej@kuh.ac.kr [Center for Neuroscience Research, SMART Institute of Advanced Biomedical Science, Konkuk University, Seoul (Korea, Republic of); Department of Rehabilitation Medicine, Konkuk University School of Medicine, Seoul (Korea, Republic of)

    2012-06-01

    Highlights: Black-Right-Pointing-Pointer 710 nm wavelength light (LED) has a protective effect in the stroke animal model. Black-Right-Pointing-Pointer We determined the effects of LED irradiation in vitro stroke model. Black-Right-Pointing-Pointer LED treatment promotes the neurite outgrowth through MAPK activation. Black-Right-Pointing-Pointer The level of synaptic markers significantly increased with LED treatment. Black-Right-Pointing-Pointer LED treatment protects cell death in the in vitro stroke model. -- Abstract: Objective: We previously reported that 710 nm Light-emitting Diode (LED) has a protective effect through cellular immunity activation in the stroke animal model. However, whether LED directly protects neurons suffering from neurodegeneration was entirely unknown. Therefore, we sought to determine the effects of 710 nm visible light irradiation on neuronal protection and neuronal outgrowth in an in vitro stroke model. Materials and methods: Primary cultured rat cortical neurons were exposed to oxygen-glucose deprivation (OGD) and reoxygenation and normal conditions. An LED array with a peak wavelength of 710 nm was placed beneath the covered culture dishes with the room light turned off and were irradiated accordingly. LED treatments (4 min at 4 J/cm{sup 2} and 50 mW/cm{sup 2}) were given once to four times within 8 h at 2 h intervals for 7 days. Mean neurite density, mean neurite diameter, and total fiber length were also measured after microtubule associated protein 2 (MAP2) immunostaining using the Axio Vision program. Synaptic marker expression and MAPK activation were confirmed by Western blotting. Results: Images captured after MAP2 immunocytochemistry showed significant (p < 0.05) enhancement of post-ischemic neurite outgrowth with LED treatment once and twice a day. MAPK activation was enhanced by LED treatment in both OGD-exposed and normal cells. The levels of synaptic markers such as PSD 95, GAP 43, and synaptophysin significantly

  2. Characterizing vulnerable plaque features with intravascular elastography.

    NARCIS (Netherlands)

    Schaar, J.A.; Korte, C.L. de; Mastik, F.; Strijder, C.; Pasterkamp, G.; Boersma, E.; Serruys, P.W.; Steen, A.F.W. van der

    2003-01-01

    BACKGROUND: In vivo detection of vulnerable plaques is presently limited by a lack of diagnostic tools. Intravascular ultrasound elastography is a new technique based on intravascular ultrasound and has the potential to differentiate between different plaques phenotypes. However, the predictive

  3. Insulin signaling regulates neurite growth during metamorphic neuronal remodeling

    Directory of Open Access Journals (Sweden)

    Tingting Gu

    2013-12-01

    Although the growth capacity of mature neurons is often limited, some neurons can shift through largely unknown mechanisms from stable maintenance growth to dynamic, organizational growth (e.g. to repair injury, or during development transitions. During insect metamorphosis, many terminally differentiated larval neurons undergo extensive remodeling, involving elimination of larval neurites and outgrowth and elaboration of adult-specific projections. Here, we show in the fruit fly, Drosophila melanogaster (Meigen, that a metamorphosis-specific increase in insulin signaling promotes neuronal growth and axon branching after prolonged stability during the larval stages. FOXO, a negative effector in the insulin signaling pathway, blocked metamorphic growth of peptidergic neurons that secrete the neuropeptides CCAP and bursicon. RNA interference and CCAP/bursicon cell-targeted expression of dominant-negative constructs for other components of the insulin signaling pathway (InR, Pi3K92E, Akt1, S6K also partially suppressed the growth of the CCAP/bursicon neuron somata and neurite arbor. In contrast, expression of wild-type or constitutively active forms of InR, Pi3K92E, Akt1, Rheb, and TOR, as well as RNA interference for negative regulators of insulin signaling (PTEN, FOXO, stimulated overgrowth. Interestingly, InR displayed little effect on larval CCAP/bursicon neuron growth, in contrast to its strong effects during metamorphosis. Manipulations of insulin signaling in many other peptidergic neurons revealed generalized growth stimulation during metamorphosis, but not during larval development. These findings reveal a fundamental shift in growth control mechanisms when mature, differentiated neurons enter a new phase of organizational growth. Moreover, they highlight strong evolutionarily conservation of insulin signaling in neuronal growth regulation.

  4. Microelectrode array-induced neuronal alignment directs neurite outgrowth: analysis using a fast Fourier transform (FFT).

    Science.gov (United States)

    Radotić, Viktorija; Braeken, Dries; Kovačić, Damir

    2017-12-01

    Many studies have shown that the topography of the substrate on which neurons are cultured can promote neuronal adhesion and guide neurite outgrowth in the same direction as the underlying topography. To investigate this effect, isotropic substrate-complementary metal-oxide-semiconductor (CMOS) chips were used as one example of microelectrode arrays (MEAs) for directing neurite growth of spiral ganglion neurons. Neurons were isolated from 5 to 7-day-old rat pups, cultured 1 day in vitro (DIV) and 4 DIV, and then fixed with 4% paraformaldehyde. For analysis of neurite alignment and orientation, fast Fourier transformation (FFT) was used. Results revealed that on the micro-patterned surface of a CMOS chip, neurons orient their neurites along three directional axes at 30, 90, and 150° and that neurites aligned in straight lines between adjacent pillars and mostly followed a single direction while occasionally branching perpendicularly. We conclude that the CMOS substrate guides neurites towards electrodes by means of their structured pillar organization and can produce electrical stimulation of aligned neurons as well as monitoring their neural activities once neurites are in the vicinity of electrodes. These findings are of particular interest for neural tissue engineering with the ultimate goal of developing a new generation of MEA essential for improved electrical stimulation of auditory neurons.

  5. CHLORHEXIDINE INHIBITS L1 CELL ADHESION MOLECULE MEDIATED NEURITE OUTGROWTH IN VITRO

    Science.gov (United States)

    Milstone, Aaron M.; Bamford, Penny; Aucott, Susan W.; Tang, Ningfeng; White, Kimberly R.; Bearer, Cynthia F.

    2013-01-01

    Background Chlorhexidine is a skin disinfectant that reduces skin and mucous membrane bacterial colonization and inhibits organism growth. Despite numerous studies assessing chlorhexidine safety in term infants, residual concerns have limited its use in hospitalized neonates, especially low birth weight preterm infants. The aim of this study was to assess the potential neurotoxicity of chlorhexidine on the developing central nervous system using a well-established in vitro model of neurite outgrowth that includes laminin and L1 cell adhesion molecule (L1) as neurite outgrowth promoting substrates. Methods Cerebellar granule neurons are plated on either poly L-lysine, L1 or laminin. Chlorhexidine, hexachlorophene or their excipients are added to the media. Neurons are grown for 24 h, then fixed and neurite length measured. Results Chlorhexidine significantly reduced the length of neurites grown on L1 but not laminin. Chlorhexidine concentrations as low as 125 ng/ml statistically significantly reduced neurite length on L1. Hexachlorophene did not affect neurite length. Conclusion Chlorhexidine at concentrations detected in the blood following topical applications in preterm infants specifically inhibited L1 mediated neurite outgrowth of cerebellar granule neurons. It is now vital to determine whether the blood brain barrier is permeable to chlorhexidine in preterm infants. PMID:24126818

  6. Computer vision profiling of neurite outgrowth dynamics reveals spatiotemporal modularity of Rho GTPase signaling.

    Science.gov (United States)

    Fusco, Ludovico; Lefort, Riwal; Smith, Kevin; Benmansour, Fethallah; Gonzalez, German; Barillari, Caterina; Rinn, Bernd; Fleuret, Francois; Fua, Pascal; Pertz, Olivier

    2016-01-04

    Rho guanosine triphosphatases (GTPases) control the cytoskeletal dynamics that power neurite outgrowth. This process consists of dynamic neurite initiation, elongation, retraction, and branching cycles that are likely to be regulated by specific spatiotemporal signaling networks, which cannot be resolved with static, steady-state assays. We present NeuriteTracker, a computer-vision approach to automatically segment and track neuronal morphodynamics in time-lapse datasets. Feature extraction then quantifies dynamic neurite outgrowth phenotypes. We identify a set of stereotypic neurite outgrowth morphodynamic behaviors in a cultured neuronal cell system. Systematic RNA interference perturbation of a Rho GTPase interactome consisting of 219 proteins reveals a limited set of morphodynamic phenotypes. As proof of concept, we show that loss of function of two distinct RhoA-specific GTPase-activating proteins (GAPs) leads to opposite neurite outgrowth phenotypes. Imaging of RhoA activation dynamics indicates that both GAPs regulate different spatiotemporal Rho GTPase pools, with distinct functions. Our results provide a starting point to dissect spatiotemporal Rho GTPase signaling networks that regulate neurite outgrowth. © 2016 Fusco et al.

  7. Mechanical Stresses in Carotid Plaques

    DEFF Research Database (Denmark)

    Samuel, Samuel Alberg

    simulationer, som tillod beregning af longitudinelle stress-niveauer i den fibrøse kappe. Afhandlingen indeholder tre artikler, som beskriver denne metode. Den første; “Mechanical Stresses in Carotid Plaques using MRI-Based Fluid Structure Interaction Models”, beskriver i detaljer metoden til at danne de...

  8. Ultrasound Tissue Characterization of Vulnerable Atherosclerotic Plaque

    Directory of Open Access Journals (Sweden)

    Eugenio Picano

    2015-05-01

    Full Text Available 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

  9. Red autofluorescence of dental plaque bacteria

    NARCIS (Netherlands)

    van der Veen, M. H.; Thomas, R. Z.; Huysmans, M. C. D. N. J. M.; de Soet, J. J.

    2006-01-01

    Red autofluorescence of plaque and its relation to fluorescence of a single species in the biofilm was studied. Fluorescence images of non-disclosed and disclosed plaque of 28 first-year students were captured. The plaque samples were assessed by culture methods and studied for red autofluorescence.

  10. Signaling mechanisms of neurite outgrowth induced by the cell adhesion molecules NCAM and N-cadherin

    DEFF Research Database (Denmark)

    Hansen, S M; Berezin, V; Bock, E

    2008-01-01

    extracellular guidance cues to intracellular events and thereby regulating neurite outgrowth. In this review, we focus on two CAMs, the neural cell adhesion molecule (NCAM) and N-cadherin, and their ability to mediate signaling associated with a neurite outgrowth response. In particular, we will focus on direct......Formation of appropriate neural circuits depends on a complex interplay between extracellular guiding cues and intracellular signaling events that result in alterations of cytoskeletal dynamics and a neurite growth response. Surface-expressed cell adhesion molecules (CAMs) interact...

  11. Quantitative analysis of carotid plaque vasa vasorum by CEUS and correlation with histology after endarterectomy.

    Science.gov (United States)

    Vavuranakis, Manolis; Sigala, Fragiska; Vrachatis, Dimitrios A; Papaioannou, Theodore G; Filis, Konstantinos; Kavantzas, Nikolaos; Kalogeras, Konstantinos I; Massoura, Constantina; Toufektzian, Levon; Kariori, Maria G; Vlasseros, Ioannis; Kallikazaros, Ioannis; Stefanadis, Christodoulos

    2013-05-01

    Intraplaque neovascularization and vasa vasorum (VV) proliferation contribute in the progression and rupture of atherosclerotic lesions. Contrast enhanced ultrasonography (CEUS) has been reported to attain data regarding intraplaque neovessels and VV. However, whether the detection of microbubbles by CEUS within atherosclerotic plaques truly represents microvessels is a point of concern. We aimed to evaluate stable and unstable carotid artery plaque (CAP) VV pattern by CEUS and its correlation with histology and immunochemistry. Patients with CAP scheduled for plaque endarterectomy were enrolled. CAP was initially identified by conventional ultrasonography and subsequently CEUS (harmonic ultrasound imaging with simultaneous intravenous contrast agent injection) was performed. The recorded image loops were evaluated by a semi-automated method. Plaque specimens were excised and underwent histological and immunochemical (for CD34, Vascular Endothelial Growth Factor, CD68 and CD3 antibodies) analysis. Fourteen patients (67.6 ± 10.2 years, 10 males) with a 86.9 ± 11.5 % degree of carotid artery stenosis were evaluated. Histology showed that half of the plaques were unstable. Enhancement of plaque brightness on CEUS was significant for both stable and unstable plaque subgroups (p = 0.018 for both). Immunochemistry showed that microvessels, as assessed by CD34 antibody, were more dense in unstable vs. stable plaques (36.6 ± 17.4 vs. 13.0 ± 7.2 respectively, p = 0.002). However, correlation between plaque brigthness enhancement on CEUS and microvessel density was significant only for stable (r = 0.800, p = 0.031) plaques. The identification of brightness enhacement during CEUS in carotid atherosclerotic plaques may not always reflect the presence of VV.

  12. Atherosclerotic plaque in carotid arteries in systemic lupus erythematosus: frequency and associated risk factors

    Directory of Open Access Journals (Sweden)

    Alexandre Wagner Silva de Souza

    Full Text Available CONTEXT AND OBJECTIVE: Atherosclerotic disease is an important cause of morbidity and mortality in systemic lupus erythematosus (SLE patients. No previous study has estimated carotid disease prevalence in such patients in Brazil. The aim was to evaluate the prevalence of atherosclerotic plaque in carotid arteries, in SLE patients and controls, and to verify possible associations between risk factors and carotid plaque. DESIGN AND SETTING: Cross-sectional study, at Universidade Federal de São Paulo - Escola Paulista de Medicina. METHODS: Carotid plaque prevalence was assessed by B-mode ultrasound in 82 female SLE patients of mean age 34.0 years and 62 controls of mean age 35.7 years. Plaque was defined as a distinct area of hyperechogenicity and/or focal protrusion of the vessel wall into the lumen. Risk factors for coronary disease and SLE-related variables were determined. RESULTS: 50% of patients and 29% of controls presented carotid plaque. Older age, longer disease duration, higher Systemic Lupus International Collaborating Clinics (SLICC score, higher levels of low-density lipoprotein and greater diabetes, obesity, premature ovarian failure and family history of coronary artery disease were found in patients with carotid plaque than in those without plaque. Patients with plaque were younger than controls with plaque. SLE diagnosis, obesity, older age, higher SLICC score and longer disease duration were independent risk factors for carotid plaque. CONCLUSION: Young patients with SLE present higher prevalence of carotid plaque than controls. SLE diagnosis was a significant risk factor for carotid atherosclerosis.

  13. ANALYSIS OF THE STRUCTURE OF MAGNETIC FIELDS THAT INDUCED INHIBITION OF STIMULATED NEURITE OUTGROWTH

    Science.gov (United States)

    The important experiments showing nonlinear amplitude dependences of the neurite outgrowth in pheochromocytoma nerve cells due to ELF magnetic field exposure had been carried out in a nonuniform ac magnetic field. The nonuniformity entailed larger than expected variances in magne...

  14. HDL-Mimetic PLGA Nanoparticle To Target Atherosclerosis Plaque Macrophages

    OpenAIRE

    Sanchez-Gaytan, Brenda L.; Fay, Francois; Lobatto, Mark E.; Tang, Jun; Ouimet, Mireille; Kim, YongTae; van der Staay, Susanne E. M.; van Rijs, Sarian M.; Priem, Bram; Zhang, Liangfang; Fisher, Edward A.; Moore, Kathryn J; Langer, Robert; Fayad, Zahi A.; Mulder, Willem J. M.

    2015-01-01

    High-density lipoprotein (HDL) is a natural nanoparticle that exhibits an intrinsic affinity for atherosclerotic plaque macrophages. Its natural targeting capability as well as the option to incorporate lipophilic payloads, e.g., imaging or therapeutic components, in both the hydrophobic core and the phospholipid corona make the HDL platform an attractive nanocarrier. To realize controlled release properties, we developed a hybrid polymer/HDL nanoparticle composed of a lipid/apolipoprotein co...

  15. Stickland reactions of dental plaque.

    Science.gov (United States)

    Curtis, M A; Kemp, C W; Robrish, S A; Bowen, W H

    1983-01-01

    Dental plaque samples from monkeys (Macaca fascicularis) were shown to contain proline reduction activity in coupled Stickland reactions with other amino acids and also with certain end products of bacterial glucose metabolism. The unusually high concentration of bound and free proline in the oral environment may be of importance in both the production of base and in the removal of acid from the tooth surface after dietary carbohydrate ingestion. PMID:6618673

  16. Bacterial sex in dental plaque

    Directory of Open Access Journals (Sweden)

    Ingar Olsen

    2013-06-01

    Full Text Available 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.

  17. Neurite outgrowth in cultured mouse pelvic ganglia - Effects of neurotrophins and bladder tissue.

    Science.gov (United States)

    Ekman, Mari; Zhu, Baoyi; Swärd, Karl; Uvelius, Bengt

    2017-07-01

    Neurotrophic factors regulate survival and growth of neurons. The urinary bladder is innervated via both sympathetic and parasympathetic neurons located in the major pelvic ganglion. The aim of the present study was to characterize the effects of the neurotrophins nerve growth factor (NGF), brain derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3) on the sprouting rate of sympathetic and parasympathetic neurites from the female mouse ganglion. The pelvic ganglion was dissected out and attached to a petri dish and cultured in vitro. All three factors (BDNF, NT-3 and NGF) stimulated neurite outgrowth of both sympathetic and parasympathetic neurites although BDNF and NT-3 had a higher stimulatory effect on parasympathetic ganglion cells. The neurotrophin receptors TrkA, TrkB and TrkC were all expressed in neurons of the ganglia. Co-culture of ganglia with urinary bladder tissue, but not diaphragm tissue, increased the sprouting rate of neurites. Active forms of BDNF and NT-3 were detected in urinary bladder tissue using western blotting whereas tissue from the diaphragm expressed NGF. Neurite outgrowth from the pelvic ganglion was inhibited by a TrkB receptor antagonist. We therefore suggest that the urinary bladder releases trophic factors, including BDNF and NT-3, which regulate neurite outgrowth via activation of neuronal Trk-receptors. These findings could influence future strategies for developing pharmaceuticals to improve re-innervation due to bladder pathologies. Copyright © 2017. Published by Elsevier B.V.

  18. Vulnerable Plaques, Inflammation and Newer Imaging Modalities

    Directory of Open Access Journals (Sweden)

    Bhatia V

    2003-01-01

    Full Text Available Currently, inflammation is considered to be the central player in the pathogenesis of atherosclerosis. It leads to the formation of multiple plaques in the arterial beds including coronary vasculature. Recent studies using the latest imaging techniques have shown that in patients with acute coronary syndromes (ACS multiple plaques are ruptured and have thrombus formation on them. Various factors make these plaques unstable, these include structural components of plaque like thin fibrous cap, high lipid content of the plaque core and inflammation, both localized and generalized. It has been shown that most of the ACS are caused by plaques causing non-critical stenosis as seen on traditional X-ray angiography. Also, the phenomenon of remodelling makes angiography a poor technique for plaque visualization. Hence newer modalities are required to identify these 'vulnerable plaques'. Intravascular ultrasound (IVUS, thermography and Magnetic Resonance Imaging (MRI are a few such promising techniques. Here we review the invasive and non-invasive modalities that can be helpful in the identification of these plaques before they become unstable and cause ACS, and also the available therapies to stabilize these plaques.

  19. Peptides modeled after the alpha-domain of metallothionein induce neurite outgrowth and promote survival of cerebellar granule neurons

    DEFF Research Database (Denmark)

    Asmussen, Johanne Wirenfeldt; Ambjørn, Malene; Bock, Elisabeth

    2009-01-01

    Metallothionein (MT) is a metal-binding protein capable of preventing oxidative stress and apoptotic cell death in the central nervous system of mammals, and hence is of putative therapeutic value in the treatment of neurodegenerative disorders. Recently, we demonstrated that a peptide modeled...... after the beta-domain of MT, EmtinB, induced neurite outgrowth and increased neuronal survival through binding to receptors of the low-density lipoprotein receptor family (LDLR). The present study identified two MT alpha-domain-derived peptide sequences termed EmtinAn and EmtinAc, each consisting of 14...... amino acids, as potent stimulators of neuronal differentiation and survival of primary neurons. In addition, we show that a peptide derived from the N-terminus of the MT beta-domain, EmtinBn, promotes neuronal survival. The neuritogenic and survival promoting effects of EmtinAc, similar to MT and Emtin...

  20. Preventive and therapeutic moderate aerobic exercise programs convert atherosclerotic plaques into a more stable phenotype.

    Science.gov (United States)

    Cardinot, Themis M; Lima, Thais M; Moretti, Ana I S; Koike, Marcia K; Nunes, Valeria S; Cazita, Patricia M; Krieger, Marta H; Brum, Patricia C; Souza, Heraldo P

    2016-05-15

    The mechanisms by which exercise affects atherosclerotic plaque stability remain incompletely understood. We evaluated the effects of two training protocols on both atherosclerotic plaque structure and the signaling pathways involved in plaque rupture. Male low-density lipoprotein (LDL) receptor knockout mice were fed a high-fat, high-cholesterol diet (HFD). One group was subjected to moderate exercise using a treadmill for 14weeks (preventive protocol). The other group started an exercise regimen after 16weeks of the HFD (therapeutic group). Atherosclerotic plaques within the aorta were evaluated for lipid and collagen contents, as well as for inflammatory markers. Plasma cholesterol and cytokine levels were also determined. The mice receiving a HFD developed hypercholesterolemia and atherosclerotic plaques within the aorta. The aortas from the animals in the preventive protocol exhibited smaller lipid cores and higher collagen content. These animals also exhibited lower CD40 expression within the plaques. The aortas of the mice in the therapeutic group exhibited higher collagen content, but no differences in either lipid core size or plaque size were noted. No differences in blood pressure, plasma cholesterol, cytokine levels, plaque size or metalloproteinase 9 expression were observed in the trained animals compared with the sedentary animals. Moderate aerobic exercise modified atherosclerotic plaque characteristics and converted the plaques into a more stable phenotype, increasing the collagen content in response to both exercise programs. Furthermore, moderate aerobic exercise reduced the animals' fat content and decreased the activity of the CD40-CD40L signaling pathway in the preventive group. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Vascular Plaque Determination for Stroke Risk Assessment

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-16-1-0608 TITLE: Vascular Plaque Determination for Stroke Risk Assessment PRINCIPAL INVESTIGATOR: Vince, David Geoffrey...TITLE AND SUBTITLE Vascular Plaque Determination for Stroke Risk Assessment 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-16-1-0608 5c. PROGRAM... plaques at high risk for initiating a cerebrovascular accident. The core of the current research project is a pilot clinical study to enroll 100 subjects

  2. Accuracy of coronary plaque detection and assessment of interobserver agreement for plaque quantification using automatic coronary plaque analysis software on coronary CT angiography

    Energy Technology Data Exchange (ETDEWEB)

    Laqmani, A.; Quitzke, M.; Creder, D.D.; Adam, G.; Lund, G. [University Medical Center Hamburg-Eppendorf, Hamburg (Germany). Dept. of Diagnostic and Interventional Radiology and Nuclearmedicine; Klink, T. [Wuerzburg Univ. (Germany). Inst. of Diagnostic and Interventional Radiology

    2016-10-15

    To evaluate the accuracy of automatic plaque detection and the interobserver agreement of automatic versus manually adjusted quantification of coronary plaques on coronary CT angiography (cCTA) using commercially available software. 10 cCTA datasets were evaluated using plaque software. First, the automatically detected plaques were verified. Second, two observers independently performed plaque quantification without revising the automatically constructed plaque contours (automatic approach). Then, each observer adjusted the plaque contours according to plaque delineation (adjusted approach). The interobserver agreement of both approaches was analyzed. 32 of 114 automatically identified findings were true-positive plaques, while 82 (72 %) were false-positive. 20 of 52 plaques (38 %) were missed by the software (false-negative). The automatic approach provided good interobserver agreement with relative differences of 0.9 ± 16.0 % for plaque area and -3.3 ± 33.8 % for plaque volume. Both observers independently adjusted all contours because they did not represent the plaque delineation. Interobserver agreement decreased for the adjusted approach with relative differences of 25.0 ± 24.8 % for plaque area and 20.0 ± 40.4 % for plaque volume. The automatic plaque analysis software is of limited value due to high numbers of false-positive and false-negative plaque findings. The automatic approach was reproducible but it necessitated adjustment of all constructed plaque contours resulting in deterioration of the interobserver agreement.

  3. Noninvasive characterization of carotid plaque strain.

    Science.gov (United States)

    Khan, Amir A; Sikdar, Siddhartha; Hatsukami, Thomas; Cebral, Juan; Jones, Michael; Huston, John; Howard, George; Lal, Brajesh K

    2017-06-01

    Current risk stratification of internal carotid artery plaques based on diameter-reducing percentage stenosis may be unreliable because ischemic stroke results from plaque disruption with atheroembolization. Biomechanical forces acting on the plaque may render it vulnerable to rupture. The feasibility of ultrasound-based quantification of plaque displacement and strain induced by hemodynamic forces and their relationship to high-risk plaques have not been determined. We studied the feasibility and reliability of carotid plaque strain measurement from clinical B-mode ultrasound images and the relationship of strain to high-risk plaque morphology. We analyzed carotid ultrasound B-mode cine loops obtained in patients with asymptomatic ≥50% stenosis during routine clinical scanning. Optical flow methods were used to quantify plaque motion and shear strain during the cardiac cycle. The magnitude (maximum absolute shear strain rate [MASSR]) and variability (entropy of shear strain rate [ESSR] and variance of shear strain rate [VSSR]) of strain were combined into a composite shear strain index (SSI), which was assessed for interscan repeatability and correlated with plaque echolucency. Nineteen patients (mean age, 70 years) constituting 36 plaques underwent imaging; 37% of patients (n = 7) showed high strain (SSI ≥0.5; MASSR, 2.2; ESSR, 39.7; VSSR, 0.03) in their plaques; the remaining clustered into a low-strain group (SSI <0.5; MASSR, 0.58; ESSR, 21.2; VSSR, 0.002). The area of echolucent morphology was greater in high-strain plaques vs low-strain plaques (28% vs 17%; P = .018). Strain measurements showed low variability on Bland-Altman plots with cluster assignment agreement of 76% on repeated scanning. Two patients developed a stroke during 2 years of follow-up; both demonstrated high SSI (≥0.5) at baseline. Carotid plaque strain is reliably computed from routine B-mode imaging using clinical ultrasound machines. High plaque strain correlates with known

  4. Association between Human Plasma Chondroitin Sulfate Isomers and Carotid Atherosclerotic Plaques

    Directory of Open Access Journals (Sweden)

    Elisabetta Zinellu

    2012-01-01

    Full Text Available Several studies have evidenced variations in plasma glycosaminoglycans content in physiological and pathological conditions. In normal human plasma GAGs are present mainly as undersulfated chondroitin sulfate (CS. The aim of the present study was to evaluate possible correlations between plasma CS level/structure and the presence/typology of carotid atherosclerotic lesion. Plasma CS was purified from 46 control subjects and 47 patients undergoing carotid endarterectomy showing either a soft or a hard plaque. The concentration and structural characteristics of plasma CS were assessed by capillary electrophoresis of constituent unsaturated fluorophore-labeled disaccharides. Results showed that the concentration of total CS isomers was increased by 21.4% (P<0.01 in plasma of patients, due to a significant increase of undersulfated CS. Consequently, in patients the plasma CS charge density was significantly reduced with respect to that of controls. After sorting for plaque typology, we found that patients with soft plaques and those with hard ones differently contribute to the observed changes. In plasma from patients with soft plaques, the increase in CS content was not associated with modifications of its sulfation pattern. On the contrary, the presence of hard plaques was associated with CS sulfation pattern modifications in presence of quite normal total CS isomers levels. These results suggest that the plasma CS content and structure could be related to the presence and the typology of atherosclerotic plaque and could provide a useful diagnostic tool, as well as information on the molecular mechanisms responsible for plaque instability.

  5. Micropatterned coumarin polyester thin films direct neurite orientation.

    Science.gov (United States)

    McCormick, Aleesha M; Maddipatla, Murthy V S N; Shi, Shuojia; Chamsaz, Elaheh A; Yokoyama, Hiroshi; Joy, Abraham; Leipzig, Nic D

    2014-11-26

    Guidance and migration of cells in the nervous system is imperative for proper development, maturation, and regeneration. In the peripheral nervous system (PNS), it is challenging for axons to bridge critical-sized injury defects to achieve repair and the central nervous system (CNS) has a very limited ability to regenerate after injury because of its innate injury response. The photoreactivity of the coumarin polyester used in this study enables efficient micropatterning using a custom digital micromirror device (DMD) and has been previously shown to be biodegradable, making these thin films ideal for cell guidance substrates with potential for future in vivo applications. With DMD, we fabricated coumarin polyester thin films into 10×20 μm and 15×50 μm micropatterns with depths ranging from 15 to 20 nm to enhance nervous system cell alignment. Adult primary neurons, oligodendrocytes, and astrocytes were isolated from rat brain tissue and seeded onto the polymer surfaces. After 24 h, cell type and neurite alignment were analyzed using phase contrast and fluorescence imaging. There was a significant difference (pdistribution for both emergence angle (from the body of the cell) and orientation angle (at the tip of the growth cone) confirming alignment on patterned surfaces compared to control substrates (unpatterned polymer and glass surfaces). The expected frequency distribution for parallel alignment (≤15°) is 14% and the two micropatterned groups ranged from 42 to 49% alignment for emergence and orientation angle measurements, where the control groups range from 12 to 22% for parallel alignment. Despite depths being 15 to 20 nm, cell processes could sense these topographical changes and preferred to align to certain features of the micropatterns like the plateau/channel interface. As a result this initial study in utilizing these new DMD micropatterned coumarin polyester thin films has proven beneficial as an axon guidance platform for future nervous system

  6. OSA and coronary plaque characteristics.

    Science.gov (United States)

    Tan, Adeline; Hau, William; Ho, Hee-Hwa; Ghaem Maralani, Haleh; Loo, Germaine; Khoo, See-Meng; Tai, Bee-Choo; Richards, A Mark; Ong, Paul; Lee, Chi-Hang

    2014-02-01

    Virtual histology intravascular ultrasound (VH-IVUS) is an intravascular imaging technique that enables the characterization of coronary plaques. We sought to determine the association between OSA and coronary plaque characteristics in patients presenting with coronary artery disease. We prospectively recruited patients with angiographically proven coronary artery disease for a VH-IVUS examination and home-based sleep study. The total atheroma volume of the entire target coronary artery and the incidence of thin cap fibroatheroma of patients with no to mild and moderate to severe OSA were compared. One hundred eighteen patients were recruited from two university-affiliated centers. Among the 93 patients who completed the study, 32 (34.4%) had newly diagnosed moderate to severe OSA (apnea-hypopnea index > 15). Compared with patients with no to mild OSA, those with moderate to severe OSA had a larger total atheroma volume (461.3 ± 250.4 mm³ vs 299.2 ± 135.6 mm³, P OSA and no to mild OSA regarding the prevalence of thin cap fibroatheroma in the culprit lesion (53.1% vs 54.2%, P = .919). In patients presenting with coronary artery disease, moderate to severe OSA was independently associated with a larger total atheroma volume in the target coronary artery. Further studies on the effects of CPAP on total atheroma volume are warranted. ClinicalTrials.gov; No.: NCT01306526; URL: www.clinicaltrials.gov.

  7. Effects of organophosphates on cholinesterase activity and neurite regeneration in Aplysia.

    Science.gov (United States)

    Srivatsan, M

    1999-05-14

    In Aplysia, a marine mollusc, acetylcholinesterase (AChE) is present in cholinergic and non-cholinergic neurons and in hemolymph. Aplysia hemolymph has a very high level of AChE which promotes neurite growth in primary cultures of dopaminergic neurons via a non-catalytic mechanism. In contrast, AChE is known to facilitate neurite growth in cholinoceptive neurons by hydrolyzing ACh which inhibits neurite growth. In order to test whether AChE's site-specific neurotrophic action varies with the neuronal phenotype, we investigated the effects of active-site inhibited hemolymph AChE on neurite growth of cholinergic neurons of Aplysia in primary culture. Organophosphates being long-acting active site inhibitors of AChE were chosen for this study. The effects of active site inhibited hemolymph AChE was tested on large cholinergic neurons, R2 (abdominal ganglion) and LPL1 (left pleural ganglion) as well as small cholinergic neurons (buccal ganglion) of Aplysia, maintained in culture. Partially purified hemolymph AChE was inhibited by either 10 microM of echothiophate or 5 microM of paraoxon. Neurons were maintained in (1) L15 (defined medium) alone; (2) L15 + echothiophate; (3) L-15 + paraoxon; (4) L-15 + hemolymph AChE; (5) L15 + hemolymph AChE + echothiophate; and (6) L-15 + hemolymph AChE + paraoxon. Addition of uninhibited hemolymph AChE significantly increased neurite growth of cultured neurons compared to L15 alone. In the presence of echothiophate-inhibited or praoxon-inhibited AChE, neurite growth was significantly reduced when compared to L15 + uninhibited AChE. While the presence of echothiophate by itself did not reduce survival or neurite growth when compared to L-15 alone, the presence of paraoxon by itself markedly reduced survival and neurite growth of cultured neurons. The results show that AChE's catalytic action contributes to enhance neurite growth in cholinergic neurons and the effects of paraoxon appears to differ from that of echothiophate on

  8. Effect of rosuvastatin on inflammatory factors and carotid atherosclerotic plaque in patients with acute ischemic stroke

    Directory of Open Access Journals (Sweden)

    YAN Jun

    2013-10-01

    Full Text Available Carotid atherosclerosis is closely related with ischemic stroke occurrence, development and recurrence. This study aims to make an evaluation of the effects of rosuvastatin on inflammatory factors, serum lipid and carotid atherosclerotic plaque in patients with acute ischemic stroke. In this study, 98 patients with acute ischemic stroke and carotid atherosclerosis were given oral administration of rosuvastatin calcium (10 mg once every night, and the course of treatment was 6 months. After treatment, the changes of serum high-sensitivity C-reactive protein (hs-CRP, tumor necrosis factor-alpha (TNF-α and blood lipid were measured, as well as carotid atherosclerotic intima-media thickness (IMT and the calculation of carotid atherosclerotic plaque score. According to the examination results, after 6 months' treatment with rosuvastatin, serum hs-CRP, TNF-α, total cholesterol (TC, triglyceride (TG and low-density lipoprotein cholestrol (LDL-C decreased significantly (P < 0.01, for all, while high-density lipoprotein cholestrol (HDL-C increased significantly (P < 0.01; the total number of plaque reduced, while the number of stable plaque increased (P < 0.05; carotid artery IMT and carotid artery plaque score decreased significantly (P < 0.05. There were significant differences between before and after treatment. The results of this study show that rosuvastatin plays a role in anti-inflammation and alleviates the degree of carotid atherosclerotic plaque.

  9. Current status of vulnerable plaque detection.

    LENUS (Irish Health Repository)

    Sharif, Faisal

    2012-02-01

    Critical coronary stenoses have been shown to contribute to only a minority of acute coronary syndromes (ACS) and sudden cardiac death. Autopsy studies have identified a subgroup of high-risk patients with disrupted vulnerable plaque and modest stenosis. Consequently, a clinical need exists to develop methods to identify these plaques prospectively before disruption and clinical expression of disease. Recent advances in invasive and noninvasive imaging techniques have shown the potential to identify these high-risk plaques. The anatomical characteristics of the vulnerable plaque such as thin cap fibroatheroma and lipid pool can be identified with angioscopy, high frequency intravascular ultrasound, intravascular MRI, and optical coherence tomography. Efforts have also been made to recognize active inflammation in high-risk plaques using intravascular thermography. Plaque chemical composition by measuring electromagnetic radiation using spectroscopy is also an emerging technology to detect vulnerable plaques. Noninvasive imaging with MRI, CT, and PET also holds the potential to differentiate between low and high-risk plaques. However, at present none of these imaging modalities are able to detect vulnerable plaque neither has been shown to definitively predict outcome. Nevertheless in contrast, there has been a parallel development in the physiological assessment of advanced atherosclerotic coronary artery disease. Thus recent trials using fractional flow reserve in patients with modest non flow-limiting stenoses have shown that deferral of PCI with optimal medical therapy in these patients is superior to coronary intervention. Further trials are needed to provide more information regarding the natural history of high-risk but non flow-limiting plaque to establish patient-specific targeted therapy and to refine plaque stabilizing strategies in the future.

  10. Plaquing procedure for infectious hematopoietic necrosis virus

    Science.gov (United States)

    Burke, J.A.; Mulcahy, D.

    1980-01-01

    A single overlay plaque assay was designed and evaluated for infectious hematopoietic necrosis virus. Epithelioma papillosum carpio cells were grown in normal atmosphere with tris(hydroxymethyl)aminomethane- or HEPES (N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid)-buffered media. Plaques were larger and formed more quickly on 1- to 3-day-old cell monolayers than on older monolayers. Cell culture medium with a 10% addition of fetal calf serum (MEM 10) or without serum (MEM 0) were the most efficient virus diluents. Dilution with phosphate-buffered saline, saline, normal broth, or deionized water reduced plaque numbers. Variations in the pH (7.0 to 8.0) of a MEM 0 diluent did not affect plaque numbers. Increasing the volume of viral inoculum above 0.15 ml (15- by 60-mm plate) decreased plaquing efficiency. Significantly more plaques occurred under gum tragacanth and methylcellulose than under agar or agarose overlays. Varying the pH (6.8 to 7.4) of methylcellulose overlays did not significantly change plaque numbers. More plaques formed under the thicker overlays of both methylcellulose and gum tragacanth. Tris(hydroxymethyl)aminomethane and HEPES performed equally well, buffering either medium or overlay. Plaque numbers were reduced when cells were rinsed after virus adsorption or less than 1 h was allowed for adsorption. Variation in adsorption time between 60 and 180 min did not change plaque numbers. The mean plaque formation time was 7 days at 16 degrees C. The viral dose response was linear when the standardized assay was used.

  11. Berberine regulates neurite outgrowth through AMPK-dependent pathways by lowering energy status

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Jiaqi; Cao, Yuanzhao; Cheng, Kuoyuan; Xu, Bo; Wang, Tianchang; Yang, Qi; Yang, Qin [State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing (China); Feng, Xudong, E-mail: xudong.feng@childrens.harvard.edu [Department of Medicine, Children' s Hospital Boston, Harvard Medical School, 300 Longwood Ave, Boston, MA 02115 (United States); Xia, Qing, E-mail: xqing@hsc.pku.edu.cn [State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing (China)

    2015-06-10

    As a widely used anti-bacterial agent and a metabolic inhibitor as well as AMP-activated protein kinase (AMPK) activator, berberine (BBR) has been shown to cross the blood–brain barrier. Its efficacy has been investigated in various disease models of the central nervous system. Neurite outgrowth is critical for nervous system development and is a highly energy-dependent process regulated by AMPK-related pathways. In the present study, we aimed to investigate the effects of BBR on AMPK activation and neurite outgrowth in neurons. The neurite outgrowth of primary rat cortical neurons at different stages of polarization was monitored after exposure of BBR. Intracellular energy level, AMPK activation and polarity-related pathways were also inspected. The results showed that BBR suppressed neurite outgrowth and affected cytoskeleton stability in the early stages of neuronal polarization, which was mediated by lowered energy status and AMPK activation. Liver kinase B1 and PI3K–Akt–GSK3β signaling pathways were also involved. In addition, mitochondrial dysfunction and endoplasmic reticulum stress contributed to the lowered energy status induced by BBR. This study highlighted the knowledge of the complex activities of BBR in neurons and corroborated the significance of energy status during the neuronal polarization. - Highlights: • BBR inhibited neurite outgrowth in early stages of neuronal development. • Lowered neuronal energy status was induced by BBR treatment. • Neuronal energy stress induced by BBR activated AMPK-related pathways. • BBR induced mitochondrial dysfunction and endoplasmic reticulum stress.

  12. Lignosus rhinocerus (Cooke Ryvarden: A Medicinal Mushroom That Stimulates Neurite Outgrowth in PC-12 Cells

    Directory of Open Access Journals (Sweden)

    Lee-Fang Eik

    2012-01-01

    Full Text Available A national treasure mushroom, Lignosus rhinocerus, has been used to treat variety of ailments by local and indigenous communities in Malaysia. The aim of this study was to investigate the potential of the most valuable part of L. rhinocerus, the sclerotium, on neurite outgrowth activity by using PC-12Adh cell line. Differentiated cells with one thin extension at least double the length of the cell diameter were scored positive. Our results showed that aqueous sclerotium L. rhinocerus extract induced neurite outgrowths of 24.4% and 42.1% at 20 μg/mL (w/v of aqueous extract alone and a combination of 20 μg/mL (w/v aqueous extract and 30 ng/mL (w/v of NGF, respectively. Combination of NGF and sclerotium extract had additive effects and enhanced neurite outgrowth. Neuronal differentiation was demonstrated by indirect immunofluorescence of neurofilament protein. Aqueous sclerotium extract contained neuroactive compounds that stimulated neurite outgrowth in vitro. To our knowledge this is the first report on neurite-stimulating activities of L. rhinocerus.

  13. Coronary plaque quantification and composition in asymptomatic patients with type II diabetes mellitus.

    Science.gov (United States)

    Manfrini, Olivia; Russo, Vincenzo; Ciavarella, Adolfo; Ceroni, Luana; Montalti, Maurizio; Fattori, Rossella

    2012-07-01

    The aim of this study was to characterize the extent and morphology of coronary lesions in asymptomatic patients with type II diabetes mellitus. We enrolled 102 asymptomatic patients with type II diabetes mellitus and 97 patients without diabetes as controls. All individuals had no history of ischemic heart disease. They underwent multidetector computed tomography (MDCT). Plaque density and plaque volume were calculated using specific software on axial images. Arterial remodeling was evaluated with semiquantitative assessment on image reconstructions. MDCT angiography revealed the presence of 124 coronary plaques in 46 patients with type II diabetes mellitus and 59 plaques in 21 controls (PDiabetic patients had a significantly higher proportion of lesions with impaired adaptive remodeling (56.5 versus 35.6%, Pdiabetic patients and 0.08 cm (0.01-0.33) in controls (P=0.14). The calcium volume was 0.082 cm (0-0.558) in diabetic patients and 0.12 cm (0-0.669) in controls (P=0.21). Plaques with fibrofatty components had a significantly higher density in the diabetic cohort (58.76  ±  9.55  Hounsfield Units), as compared with the control group (47.31  ±  5.42 Hounsfield Units, PII diabetes mellitus (r=0.37, P=0.044), but was independent of age, sex, hypertension and metabolic profile. In the control group, plaque density was independent of any covariate. Coronary plaques in type II diabetes mellitus show a tendency to develop impaired adaptive remodeling and to have a higher tissue density.

  14. LDL receptor-related protein-1 is a sialic-acid-independent receptor for myelin-associated glycoprotein that functions in neurite outgrowth inhibition by MAG and CNS myelin.

    Science.gov (United States)

    Stiles, Travis L; Dickendesher, Travis L; Gaultier, Alban; Fernandez-Castaneda, Anthony; Mantuano, Elisabetta; Giger, Roman J; Gonias, Steven L

    2013-01-01

    In the injured adult mammalian central nervous system (CNS), products are generated that inhibit neuronal sprouting and regeneration. In recent years, most attention has focused on the myelin-associated inhibitory proteins (MAIs) Nogo-A, OMgp, and myelin-associated glycoprotein (MAG). Binding of MAIs to neuronal cell-surface receptors leads to activation of RhoA, growth cone collapse, and neurite outgrowth inhibition. In the present study, we identify low-density lipoprotein (LDL) receptor-related protein-1 (LRP1) as a high-affinity, endocytic receptor for MAG. In contrast with previously identified MAG receptors, binding of MAG to LRP1 occurs independently of terminal sialic acids. In primary neurons, functional inactivation of LRP1 with receptor-associated protein, depletion by RNA interference (RNAi) knock-down, or LRP1 gene deletion is sufficient to significantly reverse MAG and myelin-mediated inhibition of neurite outgrowth. Similar results are observed when LRP1 is antagonized in PC12 and N2a cells. By contrast, inhibiting LRP1 does not attenuate inhibition of neurite outgrowth caused by chondroitin sulfate proteoglycans. Mechanistic studies in N2a cells showed that LRP1 and p75NTR associate in a MAG-dependent manner and that MAG-mediated activation of RhoA may involve both LRP1 and p75NTR. LRP1 derivatives that include the complement-like repeat clusters CII and CIV bind MAG and other MAIs. When CII and CIV were expressed as Fc-fusion proteins, these proteins, purified full-length LRP1 and shed LRP1 all attenuated the inhibition of neurite outgrowth caused by MAG and CNS myelin in primary neurons. Collectively, our studies identify LRP1 as a novel MAG receptor that functions in neurite outgrowth inhibition.

  15. Carotid plaque thickness and carotid plaque burden predict future cardiovascular events in asymptomatic adult Americans

    DEFF Research Database (Denmark)

    Sillesen, Henrik; Sartori, Samantha; Sandholt, Benjamin

    2018-01-01

    Introduction: Prediction of cardiovascular events improves using imaging, i.e. coronary calcium score and ultrasound assessment of carotid plaque. This study analysed the predictive value of two ultrasound measures of carotid plaque size: carotid plaque thickness and carotid and intima......-media thickness (IMT). Methods and results: A total of 6102 asymptomatic persons underwent assessment of conventional risk factors and imaging by carotid ultrasound. Carotid plaque burden (cPB) and maximum carotid plaque thickness (cPTmax) were measured from 'cross-sectional sweep' video acquisition...

  16. Oral biofilm models for mechanical plaque removal

    NARCIS (Netherlands)

    Verkaik, Martinus J.; Busscher, Henk J.; Rustema-Abbing, Minie; Slomp, Anje M.; Abbas, Frank; van der Mei, Henny C.

    In vitro plaque removal studies require biofilm models that resemble in vivo dental plaque. Here, we compare contact and non-contact removal of single and dual-species biofilms as well as of biofilms grown from human whole saliva in vitro using different biofilm models. Bacteria were adhered to a

  17. The role of the cytoskeleton in volume regulation and beading transitions in PC12 neurites

    CERN Document Server

    Fernandez, Pablo

    2010-01-01

    We present investigations on volume regulation and beading shape transitions in PC12 neurites conducted using a flow-chamber technique. By disrupting the cell cytoskeleton with specific drugs we investigate the role of its individual components in the volume regulation response. We find that microtubule disruption increases both swelling rate and maximum volume attained, but does not affect the ability of the neurite to recover its initial volume. In addition, investigation of axonal beading --also known as pearling instability-- provides additional clues on the mechanical state of the neurite. We conclude that the initial swelling phase is mechanically slowed down by microtubules, while the volume recovery is driven by passive diffusion of osmolites. Our experiments provide a framework to investigate the role of cytoskeletal mechanics in volume homeostasis.

  18. Nonculprit Plaque Characteristics in Patients With Acute Coronary Syndrome Caused by Plaque Erosion vs Plaque Rupture: A 3-Vessel Optical Coherence Tomography Study.

    Science.gov (United States)

    Sugiyama, Tomoyo; Yamamoto, Erika; Bryniarski, Krzysztof; Xing, Lei; Lee, Hang; Isobe, Mitsuaki; Libby, Peter; Jang, Ik-Kyung

    2018-02-07

    Patients with culprit plaque rupture are known to have pancoronary plaque vulnerability. However, the characteristics of nonculprit plaques in patients with acute coronary syndromes caused by plaque erosion are unknown. To investigate the nonculprit plaque phenotype in patients with acute coronary syndrome according to culprit plaque pathology (erosion vs rupture) by 3-vessel optical coherence tomography imaging. In this observational cohort study, between August 2010 and May 2014, 82 patients with ACS who underwent preintervention optical coherence tomography imaging of all 3 major epicardial coronary arteries were enrolled at the Massachusetts General Hospital Optical Coherence Tomography Registry database. Analysis of the data was conducted between November 2016 and July 2017. Patients were classified into 2 groups based on the culprit lesion pathology: 17 patients with culprit plaque erosion and 34 patients with culprit plaque rupture. Thirty-one patients with the absence of culprit rupture or erosion were excluded from further analysis. Preintervention 3-vessel optical coherence tomography imaging. Plaque characteristics at the culprit and nonculprit lesions evaluated by optical coherence tomography. In 51 patients (37 men; mean age, 58.7 years), the characteristics of 51 culprit plaques and 216 nonculprit plaques were analyzed. In patients with culprit erosion, the mean (SD) number of nonculprit plaques per patient was smaller (3.4 [1.9] in erosion vs 4.7 [2.1] in rupture, P = .05). Patient-based analysis showed that none of 17 patients with culprit plaque erosion had nonculprit plaque rupture, whereas 26% of the patients (9 of 34) with culprit plaque rupture had nonculprit plaque rupture (P = .02). Plaque-based analysis showed that, compared with the culprit rupture group (n = 158), the culprit erosion group (n = 58) had lower prevalence of plaque rupture (0% vs 8%; P erosion had a smaller number of nonculprit plaques and the lower levels

  19. ALS/FTLD-linked TDP-43 regulates neurite morphology and cell survival in differentiated neurons

    Energy Technology Data Exchange (ETDEWEB)

    Han, Jeong-Ho; Yu, Tae-Hoon; Ryu, Hyun-Hee; Jun, Mi-Hee; Ban, Byung-Kwan [Department of Biotechnology, College of Life Science and Nanotechnology, Hannam University, Dajeon 305-811 (Korea, Republic of); Jang, Deok-Jin [Department of Applied Biology, College of Ecology and Environment, Kyungpook National University, 386, Gajang-dong, Sangju-si, Kyungbuk 742-711 (Korea, Republic of); Lee, Jin-A, E-mail: leeja@hnu.kr [Department of Biotechnology, College of Life Science and Nanotechnology, Hannam University, Dajeon 305-811 (Korea, Republic of)

    2013-08-01

    Tar-DNA binding protein of 43 kDa (TDP-43) has been characterized as a major component of protein aggregates in brains with neurodegenerative diseases such as frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). However, physiological roles of TDP-43 and early cellular pathogenic effects caused by disease associated mutations in differentiated neurons are still largely unknown. Here, we investigated the physiological roles of TDP-43 and the effects of missense mutations associated with diseases in differentiated cortical neurons. The reduction of TDP-43 by siRNA increased abnormal neurites and decreased cell viability. ALS/FTLD-associated missense mutant proteins (A315T, Q331K, and M337V) were partially mislocalized to the cytosol and neurites when compared to wild-type and showed abnormal neurites similar to those observed in cases of loss of TDP-43. Interestingly, cytosolic expression of wild-type TDP-43 with mutated nuclear localization signals also induced abnormal neurtie morphology and reduction of cell viability. However, there was no significant difference in the effects of cytosolic expression in neuronal morphology and cell toxicity between wild-type and missense mutant proteins. Thus, our results suggest that mislocalization of missense mutant TDP-43 may contribute to loss of TDP-43 function and affect neuronal morphology, probably via dominant negative action before severe neurodegeneration in differentiated cortical neurons. Highlights: • The function of nuclear TDP-43 in neurite morphology in mature neurons. • Partial mislocalization of TDP-43 missense mutants into cytosol from nucleus. • Abnormal neurite morphology caused by missense mutants of TDP-43. • The effect of cytosolic expression of TDP-43 in neurite morphology and in cell survival.

  20. Diazinon and diazoxon impair the ability of astrocytes to foster neurite outgrowth in primary hippocampal neurons

    Energy Technology Data Exchange (ETDEWEB)

    Pizzurro, Daniella M.; Dao, Khoi [Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA (United States); Costa, Lucio G. [Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA (United States); Department of Neuroscience, University of Parma, Parma (Italy)

    2014-02-01

    Evidence from in vivo and epidemiological studies suggests that organophosphorus insecticides (OPs) are developmental neurotoxicants, but possible underlying mechanisms are still unclear. Astrocytes are increasingly recognized for their active role in normal neuronal development. This study sought to investigate whether the widely-used OP diazinon (DZ), and its oxygen metabolite diazoxon (DZO), would affect glial–neuronal interactions as a potential mechanism of developmental neurotoxicity. Specifically, we investigated the effects of DZ and DZO on the ability of astrocytes to foster neurite outgrowth in primary hippocampal neurons. The results show that both DZ and DZO adversely affect astrocyte function, resulting in inhibited neurite outgrowth in hippocampal neurons. This effect appears to be mediated by oxidative stress, as indicated by OP-induced increased reactive oxygen species production in astrocytes and prevention of neurite outgrowth inhibition by antioxidants. The concentrations of OPs were devoid of cytotoxicity, and cause limited acetylcholinesterase inhibition in astrocytes (18 and 25% for DZ and DZO, respectively). Among astrocytic neuritogenic factors, the most important one is the extracellular matrix protein fibronectin. DZ and DZO decreased levels of fibronectin in astrocytes, and this effect was also attenuated by antioxidants. Underscoring the importance of fibronectin in this context, adding exogenous fibronectin to the co-culture system successfully prevented inhibition of neurite outgrowth caused by DZ and DZO. These results indicate that DZ and DZO increase oxidative stress in astrocytes, and this in turn modulates astrocytic fibronectin, leading to impaired neurite outgrowth in hippocampal neurons. - Highlights: • DZ and DZO inhibit astrocyte-mediated neurite outgrowth in rat hippocampal neurons. • Oxidative stress is involved in inhibition of neuritogenesis by DZ and DZO. • DZ and DZO decrease expression of the neuritogenic

  1. HDL-mimetic PLGA nanoparticle to target atherosclerosis plaque macrophages.

    Science.gov (United States)

    Sanchez-Gaytan, Brenda L; Fay, Francois; Lobatto, Mark E; Tang, Jun; Ouimet, Mireille; Kim, YongTae; van der Staay, Susanne E M; van Rijs, Sarian M; Priem, Bram; Zhang, Liangfang; Fisher, Edward A; Moore, Kathryn J; Langer, Robert; Fayad, Zahi A; Mulder, Willem J M

    2015-03-18

    High-density lipoprotein (HDL) is a natural nanoparticle that exhibits an intrinsic affinity for atherosclerotic plaque macrophages. Its natural targeting capability as well as the option to incorporate lipophilic payloads, e.g., imaging or therapeutic components, in both the hydrophobic core and the phospholipid corona make the HDL platform an attractive nanocarrier. To realize controlled release properties, we developed a hybrid polymer/HDL nanoparticle composed of a lipid/apolipoprotein coating that encapsulates a poly(lactic-co-glycolic acid) (PLGA) core. This novel HDL-like nanoparticle (PLGA-HDL) displayed natural HDL characteristics, including preferential uptake by macrophages and a good cholesterol efflux capacity, combined with a typical PLGA nanoparticle slow release profile. In vivo studies carried out with an ApoE knockout mouse model of atherosclerosis showed clear accumulation of PLGA-HDL nanoparticles in atherosclerotic plaques, which colocalized with plaque macrophages. This biomimetic platform integrates the targeting capacity of HDL biomimetic nanoparticles with the characteristic versatility of PLGA-based nanocarriers.

  2. Fibrillar amyloid plaque formation precedes microglial activation.

    Science.gov (United States)

    Jung, Christian K E; Keppler, Kevin; Steinbach, Sonja; Blazquez-Llorca, Lidia; Herms, Jochen

    2015-01-01

    In Alzheimer's disease (AD), hallmark β-amyloid deposits are characterized by the presence of activated microglia around them. Despite an extensive characterization of the relation of amyloid plaques with microglia, little is known about the initiation of this interaction. In this study, the detailed investigation of very small plaques in brain slices in AD transgenic mice of the line APP-PS1(dE9) revealed different levels of microglia recruitment. Analysing plaques with a diameter of up to 10 μm we find that only the half are associated with clear morphologically activated microglia. Utilizing in vivo imaging of new appearing amyloid plaques in double-transgenic APP-PS1(dE9)xCX3CR1+/- mice further characterized the dynamic of morphological microglia activation. We observed no correlation of morphological microglia activation and plaque volume or plaque lifetime. Taken together, our results demonstrate a very prominent variation in size as well as in lifetime of new plaques relative to the state of microglia reaction. These observations might question the existing view that amyloid deposits by themselves are sufficient to attract and activate microglia in vivo.

  3. A simple immunoperoxidase plaque assay to detect and quantitate Marek's disease virus plaques.

    Science.gov (United States)

    Silva, R F; Calvert, J G; Lee, L F

    1997-01-01

    We report an immunoperoxidase-based staining technique that can be used to rapidly and accurately detect and quantitate Marek's disease virus (MDV) plaques. Monolayer cultures were fixed and incubated with a monoclonal antibody specific for MDV. After washing, a second antibody of horseradish peroxidase-conjugated goat anti-mouse IgG was applied, incubated for 1 hr, and washed with phosphate-buffered saline. After the cultures were incubated with diaminobenzidine, CoCl2, and H2O2, the plaques appeared as black spots and were easily seen and counted. Significantly more immunoperoxidase-stained serotype 1 MDV plaques could be counted at 4 days postinoculation than were seen in unstained cultures. With serotype 2 MDV-infected cells, the difference in plaque counts was less dramatic. Nevertheless, at 3 days postinoculation, significantly more stained serotype 2 plaques were seen than unstained plaques. Immunoperoxidase staining of turkey herpesvirus plaques did not increase the sensitivity of viewing plaques. Similar numbers of stained and unstained plaques were seen at 2 days postinoculation. We also demonstrated that we could count serotype-specific MDV plaques in a mixed infection that contained all three serotypes.

  4. Regional brain hypometabolism is unrelated to regional amyloid plaque burden.

    Science.gov (United States)

    Altmann, Andre; Ng, Bernard; Landau, Susan M; Jagust, William J; Greicius, Michael D

    2015-12-01

    In its original form, the amyloid cascade hypothesis of Alzheimer's disease holds that fibrillar deposits of amyloid are an early, driving force in pathological events leading ultimately to neuronal death. Early clinicopathological investigations highlighted a number of inconsistencies leading to an updated hypothesis in which amyloid plaques give way to amyloid oligomers as the driving force in pathogenesis. Rather than focusing on the inconsistencies, amyloid imaging studies have tended to highlight the overlap between regions that show early amyloid plaque signal on positron emission tomography and that also happen to be affected early in Alzheimer's disease. Recent imaging studies investigating the regional dependency between metabolism and amyloid plaque deposition have arrived at conflicting results, with some showing regional associations and other not. We extracted multimodal neuroimaging data from the Alzheimer's disease neuroimaging database for 227 healthy controls and 434 subjects with mild cognitive impairment. We analysed regional patterns of amyloid deposition, regional glucose metabolism and regional atrophy using florbetapir ((18)F) positron emission tomography, (18)F-fluordeoxyglucose positron emission tomography and T1-weighted magnetic resonance imaging, respectively. Specifically, we derived grey matter density and standardized uptake value ratios for both positron emission tomography tracers in 404 functionally defined regions of interest. We examined the relation between regional glucose metabolism and amyloid plaques using linear models. For each region of interest, correcting for regional grey matter density, age, education and disease status, we tested the association of regional glucose metabolism with (i) cortex-wide florbetapir uptake; (ii) regional (i.e. in the same region of interest) florbetapir uptake; and (iii) regional florbetapir uptake while correcting in addition for cortex-wide florbetapir uptake. P-values for each setting

  5. Ultrasonic tissue characterization of vulnerable carotid plaque: correlation between videodensitometric method and histological examination

    Directory of Open Access Journals (Sweden)

    Cherri Jesualdo

    2006-08-01

    Full Text Available Abstract Background To establish the correlation between quantitative analysis based on B-mode ultrasound images of vulnerable carotid plaque and histological examination of the surgically removed plaque, on the basis of a videodensitometric digital texture characterization. Methods Twenty-five patients (18 males, mean age 67 ± 6.9 years admitted for carotid endarterectomy for extracranial high-grade internal carotid artery stenosis (≥ 70% luminal narrowing underwent to quantitative ultrasonic tissue characterization of carotid plaque before surgery. A computer software (Carotid Plaque Analysis Software was developed to perform the videodensitometric analysis. The patients were divided into 2 groups according to symptomatology (group I, 15 symptomatic patients; and group II, 10 patients asymptomatic. Tissue specimens were analysed for lipid, fibromuscular tissue and calcium. Results The first order statistic parameter mean gray level was able to distinguish the groups I and II (p = 0.04. The second order parameter energy also was able to distinguish the groups (p = 0,02. A histological correlation showed a tendency of mean gray level to have progressively greater values from specimens with 75% of fibrosis. Conclusion Videodensitometric computer analysis of scan images may be used to identify vulnerable and potentially unstable lipid-rich carotid plaques, which are less echogenic in density than stable or asymptomatic, more densely fibrotic plaques.

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

    Science.gov (United States)

    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.

  7. The association between gallstone disease and plaque in the abdominopelvic arteries

    Directory of Open Access Journals (Sweden)

    Halil Ibrahim Serin

    2017-01-01

    Full Text Available Background: The aim of this study was to assess the atheromatous plaque, in the abdominopelvic arteries as a marker of cardiac risk in patients with or without gallstone disease (GD. Materials and Methods: A total of 136 patients were enrolled in this cross-sectional study. Forty-eight patients had GD and the remaining 88 patients did not. The presence or absence of gallstones was noted during abdominal ultrasonography while vascular risk factors such as plaque formation, intima-media thickness, plaque calcification, mural thrombus, stenosis, aneurysm, and inflammation were recorded during an abdominopelvic computed tomography scan. In addition, percentage of the abdominopelvic aorta surface covered by atheromatous plaque was calculated. Results: The mean age of patients with GD and without GD was 50.81 ± 16.20 and 50.40 ± 12.43, respectively. Patients with GD were more likely to have diabetes mellitus, a higher body mass index (BMI (P < 0.001, and higher cholesterol (P < 0.01, and low-density lipoprotein-cholesterol (P < 0.02 levels. No significant differences were found between the groups regarding other atherosclerotic risk factors. Patients with GD had significantly higher rates of the vascular risk factors as intima-media thickness, plaque formation, calcification, aneurysm, mural thrombosis, stenosis, and inflammation in all abdominal arterial segments other than aneurysm in the femoral arteries. In addition, patients with GD had severe atheromatous plaques in the abdominal aorta, common iliac, external iliac, and common femoral artery (CFA. In patients with GD, parameters of age, BMI, and systolic and diastolic blood pressure were all correlated with the severity of the atheromatous plaque in abdominal aorta, common iliac, external iliac, and CFA. Conclusion: We demonstrated a direct relationship between GD and abdominopelvic atheromatous plaque, which is a marker for increased cardiovascular risk, for the first time in the literature

  8. Spatial Analysis of the Neuronal Density of Aminergic Brainstem Nuclei in Primary Neurodegenerative and Vascular Dementia: A Comparative Immunocytochemical and Quantitative Study Using a Graph Method

    Directory of Open Access Journals (Sweden)

    Yan Yang

    1999-01-01

    Full Text Available A graph method was employed to analyse spatial neuronal patterns of pontine nuclei with ascending aminergic projections to the forebrain (nucleus centralis superior (NCS, raphes dorsalis (NRD and locus coeruleus (LC, in Alzheimer disease (AD, Huntington disease (HD, and vascular (VD as well as “mixed‐type” (VA dementia, compared with non‐demented controls (CO and a small sample of brains from schizophrenics (“dementia praecox” (DP. The quantitative evaluations by the “minimal spanning tree (MST” were complemented by rough neurofibrillary tangle (NFT counts and by semiquantitative immunohistochemical assessment of amyloid deposition, neuritic plaque formation, and cellular gliosis. The AD cases showed a significant decline of neuronal density in all nuclei examined, as compared with controls and DP. Neuronal loss was not significant in VD, while the mixed cases with both vascular and Alzheimer‐type pathology exhibited pronounced changes of neuronal density. Amyloid deposition occurred almost exclusively in AD and VA, as a rule, being of moderate degree, except for two presenile AD cases where it was marked. NFT were significantly increased in all nuclei in AD and in the VA cases, while they only occasionally appeared beyond age 55 in HD, DP and CO. The four HD cases showed in the NCS and NRD neuronal loss as severe as in AD. This neuronal loss implicates impairment of serotoninergic and noradrenergic neuromodulation as one basic mechanism promoting dementia in AD, VA and perhaps in HD.

  9. Film dosimetry analyses on the effect of gold shielding for Iodine-125 eye plaque therapy for choroidal melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Wu, A. (Department of Radiation Oncology, University of Pittsburgh, School of Medicine, Joint Radiation Oncology Center and Pittsburgh Cancer Institute, Pittsburgh, PA (USA)); Krasin, F. (Department of Radiation Oncology, Tufts University School of Medicine, New England Medical Center, Boston, MA (USA))

    1990-09-01

    One of the methods currently being used to treat choroidal melanoma employs an episcleral plaque containing I-125 radioactive seeds. However, comprehensive dosimetry studies on the plaque are scarce and controversial. For this work, we use film to study the dosimetry outside the lip of the gold shield of the eye plaque. This lip around the gold shield was made to protect the critical structures behind and adjacent to the lesion. Since the changes of energy spectrum of I-125 in tissue are negligible, film dosimetry seems to be a logical choice because of high spatial resolution required around the lip of the gold plaque. For this study, we first established an H and D curve with dose expressed in a unit of specific dose rate constant. This avoids absolute dose measurements. All film density measurements are made with a 1-mm aperture scan, normalized to the density at the prescription point for tumor of 3--5-mm apical height, i.e., 5 mm from the interior surface of sclera, and converted to percentage isodose curves. With a gold shield, it is found that when the plaque is placed against the optical nerve, the optical disk and macula, located at 2 mm outside the lip, on the exterior surface of sclera, may receive 85% of the prescription dose for a 12-mm plaque and 58% for a 16-mm plaque. For tumors of 8-mm apical height, the optical nerve would receive more than the prescription dose.

  10. Adhesion and neurite development of cortical neurons on micropatterns of polyethylenimine and fluorcarbon

    NARCIS (Netherlands)

    Ruardij, T.G.; Goedbloed, M.H.; Rutten, Wim

    2000-01-01

    This study aims on the preparation of isolated islands of cortical neurons on modified glass surfaces. Isolated islands of cortical neurons were obtained with a combination of neuron-adhesive polyethylenimine (PEI) and neuron-repellent plasma-deposited fluorocarbon (FC). Neurite development and

  11. Mechanosensitivity of Embryonic Neurites Promotes Their Directional Extension and Schwann Cells Progenitors Migration

    Directory of Open Access Journals (Sweden)

    Gonzalo Rosso

    2017-11-01

    Full Text Available Background/Aims: Migration of Schwann cells (SCs progenitors and neurite outgrowth from embryonic dorsal root ganglions (DRGs are two central events during the development of the peripheral nervous system (PNS. How these two enthralling events preceding myelination are promoted is of great relevance from basic research and clinical aspects alike. Recent evidence demonstrates that biophysical cues (extracellular matrix stiffness and biochemical signaling act in concert to regulate PNS myelination. Microenvironment stiffness of SCs progenitors and embryonic neurites dynamically changes during development. Methods: DRG explants were isolated from day 12.5 to 13.5 mice embryos and plated on laminin-coated substrates with varied stiffness values. After 4 days in culture and immunostaining with specific markers, neurite outgrowth pattern, SCs progenitors migration, and growth cone shape and advance were analyzed with confocal fluorescence microscopy. Results: We found out that growing substrate stiffness promotes directional neurite outgrowth, SCs progenitors migration, growth cone advance and presumably axons fasciculation. Conclusions: DRG explants are in vitro models for the research of PNS development, myelination and regeneration. Consequently, we conclude the following: Our observations point out the importance of mechanosensitivity for the PNS. At the same time, they prompt the investigation of the important yet unclear links between PNS biomechanics and inherited neuropathies with myelination disorders such as Charcot-Marie-Tooth 1A and hereditary neuropathy with liability to pressure palsies. Finally, they encourage the consideration of mechanosensitivity in bioengineering of scaffolds to aid nerve regeneration after injury.

  12. Stochastic continuous time neurite branching models with tree and segment dependent rates

    NARCIS (Netherlands)

    van Elburg, Ronald A. J.

    2011-01-01

    In this paper we introduce a continuous time stochastic neurite branching model closely related to the discrete time stochastic BES-model. The discrete time BES-model is underlying current attempts to simulate cortical development, but is difficult to analyze. The new continuous time formulation

  13. Luteolin induces microRNA-132 expression and modulates neurite outgrowth in PC12 cells.

    Directory of Open Access Journals (Sweden)

    Lian-Fang Lin

    Full Text Available Luteolin (3',4',5,7-tetrahydroxyflavone, a food-derived flavonoid, has been reported to exert neurotrophic properties that are associated with its capacity to promote neuronal survival and neurite outgrowth. In this study, we report for the first time that luteolin induces the persistent expression of microRNA-132 (miR-132 in PC12 cells. The correlation between miR-132 knockdown and a decrease in luteolin-mediated neurite outgrowth may indicate a mechanistic link by which miR-132 functions as a mediator for neuritogenesis. Furthermore, we find that luteolin led to the phosphorylation and activation of cAMP response element binding protein (CREB, which is associated with the up-regulation of miR-132 and neurite outgrowth. Moreover, luteolin-induced CREB activation, miR-132 expression and neurite outgrowth were inhibited by adenylate cyclase, protein kinase A (PKA and MAPK/ERK kinase 1/2 (MEK1/2 inhibitors but not by protein kinase C (PKC or calcium/calmodulin-dependent protein kinase II (CaMK II inhibitors. Consistently, we find that luteolin treatment increases ERK phosphorylation and PKA activity in PC12 cells. These results show that luteolin induces the up-regulation of miR-132, which serves as an important regulator for neurotrophic actions, mainly acting through the activation of cAMP/PKA- and ERK-dependent CREB signaling pathways in PC12 cells.

  14. Tiam1 as a signaling mediator of nerve growth factor-dependent neurite outgrowth.

    Directory of Open Access Journals (Sweden)

    Shahrzad Shirazi Fard

    Full Text Available Nerve Growth Factor (NGF-induced neuronal differentiation requires the activation of members of the Rho family of small GTPases. However, the molecular mechanisms through which NGF regulates cytoskeletal changes and neurite outgrowth are not totally understood. In this work, we identify the Rac1-specific guanine exchange factor (GEF Tiam1 as a novel mediator of NGF/TrkA-dependent neurite elongation. In particular, we report that knockdown of Tiam1 causes a significant reduction in Rac1 activity and neurite outgrowth induced by NGF. Physical interaction between Tiam1 and active Ras (Ras-GTP, but not tyrosine phosphorylation of Tiam1, plays a central role in Rac1 activation by NGF. In addition, our findings indicate that Ras is required to associate Tiam1 with Rac1 and promote Rac1 activation upon NGF stimulation. Taken together, these findings define a novel molecular mechanism through which Tiam1 mediates TrkA signaling and neurite outgrowth induced by NGF.

  15. Patterned and functionalized nanofiber scaffolds in three-dimensional hydrogel constructs enhance neurite outgrowth and directional control.

    Science.gov (United States)

    McMurtrey, Richard J

    2014-12-01

    Neural tissue engineering holds incredible potential to restore functional capabilities to damaged neural tissue. It was hypothesized that patterned and functionalized nanofiber scaffolds could control neurite direction and enhance neurite outgrowth. A method of creating aligned electrospun nanofibers was implemented and fiber characteristics were analyzed using environmental scanning electron microscopy. Nanofibers were composed of polycaprolactone (PCL) polymer, PCL mixed with gelatin, or PCL with a laminin coating. Three-dimensional hydrogels were then integrated with embedded aligned nanofibers to support neuronal cell cultures. Microscopic images were captured at high-resolution in single and multi-focal planes with eGFP-expressing neuronal SH-SY5Y cells in a fluorescent channel and nanofiber scaffolding in another channel. Neuronal morphology and neurite tracking of nanofibers were then analyzed in detail. Aligned nanofibers were shown to enable significant control over the direction of neurite outgrowth in both two-dimensional (2D) and three-dimensional (3D) neuronal cultures. Laminin-functionalized nanofibers in 3D hyaluronic acid (HA) hydrogels enabled significant alignment of neurites with nanofibers, enabled significant neurite tracking of nanofibers, and significantly increased the distance over which neurites could extend. Specifically, the average length of neurites per cell in 3D HA constructs with laminin-functionalized nanofibers increased by 66% compared to the same laminin fibers on 2D laminin surfaces, increased by 59% compared to 2D laminin-coated surface without fibers, and increased by 1052% compared to HA constructs without fibers. Laminin functionalization of fibers also doubled average neurite length over plain PCL fibers in the same 3D HA constructs. In addition, neurites also demonstrated tracking directly along the fibers, with 66% of neurite lengths directly tracking laminin-coated fibers in 3D HA constructs, which was a 65% relative

  16. Haemodynamical stress in mouse aortic arch with atherosclerotic plaques: Preliminary study of plaque progression

    OpenAIRE

    Assemat, P.; Siu, K.K.; Armitage, J.A.; Hokke, S.N.; Dart, A; Chin-Dusting, J; Hourigan, K.

    2014-01-01

    Atherosclerotic plaques develop at particular sites in the arterial tree, and this regional localisation depends largely on haemodynamic parameters (such as wall shear stress; WSS) as described in the literature. Plaque rupture can result in heart attack or stroke and hence understanding the development and vulnerability of atherosclerotic plaques is critically important. The purpose of this study is to characterise the haemodynamics of blood flow in the mouse aortic arch using numerical mode...

  17. Sticky Brain 'Plaques' Implicated in Alzheimer's Again

    Science.gov (United States)

    ... fullstory_166550.html Sticky Brain 'Plaques' Implicated in Alzheimer's Again Researchers believe these substances form in early ... in the brain signals an early stage of Alzheimer's disease. It's been known for years that in ...

  18. Magnetic force microscopy of atherosclerotic plaque

    National Research Council Canada - National Science Library

    T A Alexeeva; S V Gorobets; O Yu Gorobets; I V Demianenko; O M Lazarenko

    2014-01-01

    In this work by methods of scanning probe microscopy, namely by atomic force microscopy and magnetic force microscopy the fragments of atherosclerotic plaque section of different nature were investigated...

  19. Evaluation of the Navy Plaque Control Program, at Great Lakes.

    Science.gov (United States)

    1980-02-01

    I 0 Individual clinicians who practice plaque control with their patients receive great reward and sense of accomplishment when dental caries is...Navy Dental Corps (43). The program requirements included plaque control instruction given through individual or small group sessions. The sessions... plaque removal techniques; demonstration of sulcular methods of tooth cleansing with the toothbrush ; and instruction in the use of plaque disclosing

  20. [Is regression of atherosclerotic plaque possible?

    Science.gov (United States)

    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.

  1. Waves of actin and microtubule polymerization drive microtubule-based transport and neurite growth before single axon formation

    Science.gov (United States)

    Winans, Amy M; Collins, Sean R; Meyer, Tobias

    2016-01-01

    Many developing neurons transition through a multi-polar state with many competing neurites before assuming a unipolar state with one axon and multiple dendrites. Hallmarks of the multi-polar state are large fluctuations in microtubule-based transport into and outgrowth of different neurites, although what drives these fluctuations remains elusive. We show that actin waves, which stochastically migrate from the cell body towards neurite tips, direct microtubule-based transport during the multi-polar state. Our data argue for a mechanical control system whereby actin waves transiently widen the neurite shaft to allow increased microtubule polymerization to direct Kinesin-based transport and create bursts of neurite extension. Actin waves also require microtubule polymerization, arguing that positive feedback links these two components. We propose that actin waves create large stochastic fluctuations in microtubule-based transport and neurite outgrowth, promoting competition between neurites as they explore the environment until sufficient external cues can direct one to become the axon. DOI: http://dx.doi.org/10.7554/eLife.12387.001 PMID:26836307

  2. Aggregation of plaque disclosing agent in a dentifrice

    OpenAIRE

    Silva, Débora Dias da; Gonçalo, Camila da Silva; Sousa, Maria da Luz Rosário de; Wada,Ronaldo Seichi

    2004-01-01

    Dental plaque removal is an important issue in health promotion. Toothbrushing is one of the main methods employed for such purpose, since it can prevent dental caries by means of the fluoride present in the dentifrice. Dentifrices might contain plaque disclosing agents and thus allow dental plaque observation. The aim of this study was to assess whether utilization of a plaque disclosing agent interfered with plaque removal among adolescents, as well as the difference between utilization of ...

  3. Carotid plaque stabilization induced by the supplement association Pycnogenol® and centella asiatica (Centellicum®).

    Science.gov (United States)

    Luzzi, Roberta; Belcaro, Gianni; Ippolito, Edmondo

    2016-12-01

    Aim of this registry study was the evaluation of the stability of carotid plaques by ultrasound in asymptomatic subjects with high oxidative stress following supplementation with a combination of the extract from bark of Pinus pinaster, Pycnogenol®, with an extract from Centella asiatica leaves, Centellicum®. 50 patients, mean age 61.5 years, with carotid plaques (<50% stenosis) and high oxidative stress were included in this 3 months registry study. 26 patients received the combination of Pycnogenol® and Centellicum® and standard management, a control group received standard management only. The 2 groups were comparable. The combination of Pycnogenol® and Centellicum® reduced significantly (p<0.05) plaque height and length as well as the number of plaques relative to controls. The plaque stability index, based on the echogenicity in the ultrasound picture of the "white" components of the plaque, increased significantly (p<0.01) in the verum group, no changes were observed in the controls. Plasma free radicals were significantly (p<0.05) decreased by the combination product, whereas the levels of plasma free radicals remained unchanged in the control group. No unwanted effects or abnormal laboratory tests were recorded. This registry study revealed a significant increase in stability of plaques, indicated by an enhanced density of the plaques, following supplementation with the combination of Pycnogenol® and Centellicum®. As size and number of plaques was simultaneously reduced, the combination of the two plant extracts could be a safe option for prevention of cardiovascular events for patients with carotid plaques.

  4. Chemical agents for the control of plaque and plaque microflora: an overview.

    Science.gov (United States)

    Gaffar, A; Afflitto, J; Nabi, N

    1997-10-01

    This presentation provides an overview of the technologies available for the chemical control of plaque. It is generally accepted that the formation of dental plaque at the interfaces of tooth/gingiva is one of the major causes of gingival inflammation and dental caries. Several therapeutic approaches have been used to control dental plaque and supragingival infections. These include fluoride preparations such as stannous fluoride, oxygenating agents, anti-attachment agents, and cationic and non-cationic antibacterial agents. Among the fluoride preparations, stable stannous fluoride pastes and gels have been shown to reduce supragingival plaque, gingivitis, hypersensitivity and caries. The effect of the oxygenating agents on the supragingival plaque has been equivocal, but recent data indicate that a stable agent which provides sustained active oxygen release is effective in controlling plaque. A polymer, PVPA, which reduced attachment of bacteria to teeth was shown to significantly reduce plaque formation in humans. A new generation of antibacterials includes non-ionics such as triclosan, which in combination with a special polymer delivery system, has been shown to reduce plaque, gingivitis, supragingival calculus and dental caries in long-term studies conducted around the world. Unlike the first generation of agents, the triclosan/copolymer/sodium fluoride system is effective in long-term clinicals and does not cause staining of teeth, increase in calculus, or disturbance in the oral microbial ecology.

  5. Decreased cathepsin K levels in human atherosclerotic plaques are associated with plaque instability.

    Science.gov (United States)

    Zhao, Huiying; Qin, Xiujiao; Wang, Shuai; Sun, Xiwei; Dong, Bin

    2017-10-01

    Investigating the determinants and dynamics of atherosclerotic plaque instability is a key area of current cardiovascular research. Extracellular matrix degradation from excessive proteolysis induced by enzymes such as cathepsin K (Cat K) is implicated in the pathogenesis of unstable plaques. The current study assessed the expression of Cat K in human unstable atherosclerotic plaques. Specimens of popliteal arteries with atherosclerotic plaques were classified as stable (K and cystatin C (Cys C) were assessed by immunohistochemical examination and levels of Cat K mRNA were detected by semi-quantitative reverse transcriptase polymerase chain reaction. Morphological changes including a larger lipid core, endothelial proliferation with foam cells and destruction of internal elastic lamina were observed in unstable atherosclerotic plaques. In unstable plaques, the expression of Cat K protein and mRNA was upregulated, whereas Cys C protein expression was downregulated. The interplay between Cat K and Cys C may underlie the progression of plaques from stable to unstable and the current study indicated that Cat K and Cys C are potential targets for preventing and treating vulnerable atherosclerotic plaque ruptures.

  6. Association between traditional cholesterol parameters, lipoprotein particle concentration, novel biomarkers and carotid plaques in retired National Football League players.

    Science.gov (United States)

    Virani, Salim S; Pompeii, Lisa; Lincoln, Andrew E; Dunn, Reginald E; Tucker, Andrew M; Nambi, Vijay; Nasir, Khurram; Vogel, Robert A; Boone, Jeffrey L; Roberts, Arthur J; Ballantyne, Christie M

    2012-06-01

    We assessed whether low-density lipoprotein particle concentration (LDL-P) and high-sensitivity C-reactive protein [hs-CRP] can identify subclinical atherosclerosis better than traditional cholesterol parameters in retired National Football League (NFL) players. It is not known whether LDL-P and the biomarker hs-CRP can identify subclinical atherosclerosis better than low-density lipoprotein cholesterol (LDL-C) or non-high-density-lipoprotein cholesterol (non-HDL-C) in retired NFL players, given high prevalence of metabolic syndrome in these players. Carotid artery plaque screening was performed with traditional lipids, LDL-P, and hs-CRP in 996 retired players. Logistic regression analyses comparing highest with the lowest quartile were performed. Carotid artery plaques were seen in 41%. LDL-C (odds ratio [OR] 1.66, 95% confidence interval [CI] 1.06-2.59), non-HDL-C (OR 1.67, 95% CI 1.04-2.67), and LDL-P (OR 2.21, 95% CI 1.35-3.62) were associated with plaques in adjusted models. Among 187 retired players with metabolic syndrome, LDL-C (OR 1.40, 95% CI 0.53-3.72) was not associated with carotid plaques, whereas LDL-P (OR 3.71, 95% CI 1.16-11.84) and non-HDL-C (OR 2.63, 95% CI 0.91-7.63, p=0.07; borderline significant) were associated with carotid plaques. hs-CRP (OR 1.13, 95% CI 0.71-1.79) was not associated with carotid plaques. Carotid artery plaques were common in retired NFL players and were strongly associated with LDL-P, especially among those with metabolic syndrome. hs-CRP was not associated with carotid plaques in this cohort. Published by Elsevier Ireland Ltd.

  7. Simulation of human atherosclerotic femoral plaque tissue: the influence of plaque material model on numerical results

    Science.gov (United States)

    2015-01-01

    Background Due to the limited number of experimental studies that mechanically characterise human atherosclerotic plaque tissue from the femoral arteries, a recent trend has emerged in current literature whereby one set of material data based on aortic plaque tissue is employed to numerically represent diseased femoral artery tissue. This study aims to generate novel vessel-appropriate material models for femoral plaque tissue and assess the influence of using material models based on experimental data generated from aortic plaque testing to represent diseased femoral arterial tissue. Methods Novel material models based on experimental data generated from testing of atherosclerotic femoral artery tissue are developed and a computational analysis of the revascularisation of a quarter model idealised diseased femoral artery from a 90% diameter stenosis to a 10% diameter stenosis is performed using these novel material models. The simulation is also performed using material models based on experimental data obtained from aortic plaque testing in order to examine the effect of employing vessel appropriate material models versus those currently employed in literature to represent femoral plaque tissue. Results Simulations that employ material models based on atherosclerotic aortic tissue exhibit much higher maximum principal stresses within the plaque than simulations that employ material models based on atherosclerotic femoral tissue. Specifically, employing a material model based on calcified aortic tissue, instead of one based on heavily calcified femoral tissue, to represent diseased femoral arterial vessels results in a 487 fold increase in maximum principal stress within the plaque at a depth of 0.8 mm from the lumen. Conclusions Large differences are induced on numerical results as a consequence of employing material models based on aortic plaque, in place of material models based on femoral plaque, to represent a diseased femoral vessel. Due to these large

  8. Characteristic detected on computed tomography angiography predict coronary artery plaque progression in non-culprit lesions

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Ya Hang; Zhou, Jia Zhou; Zhou, Ying; Yang, Xiaobo; Yang, Jun Jie; Chen, Yun Dai [Dept. of Cardiology, Chinese PLA General Hospital, Beijing (China)

    2017-06-15

    This study sought to determine whether variables detected on coronary computed tomography angiography (CCTA) would predict plaque progression in non-culprit lesions (NCL). In this single-center trial, we analyzed 103 consecutive patients who were undergoing CCTA and percutaneous coronary intervention (PCI) for culprit lesions. Follow-up CCTA was scheduled 12 months after the PCI, and all patients were followed for 3 years after their second CCTA examination. High-risk plaque features and epicardial adipose tissue (EAT) volume were assessed by CCTA. Each NCL stenosis grade was compared visually between two CCTA scans to detect plaque progression, and patients were stratified into two groups based on this. Logistic regression analysis was used to evaluate the factors that were independently associated with plaque progression in NCLs. Time-to-event curves were compared using the log-rank statistic. Overall, 34 of 103 patients exhibited NCL plaque progression (33%). Logistic regression analyses showed that the NCL progression was associated with a history of ST-elevated myocardial infarction (odds ratio [OR] = 5.855, 95% confidence interval [CI] = 1.391–24.635, p = 0.016), follow-up low-density lipoprotein cholesterol level (OR = 6.832, 95% CI = 2.103–22.200, p = 0.001), baseline low-attenuation plaque (OR = 7.311, 95% CI = 1.242–43.028, p = 0.028) and EAT (OR = 1.015, 95% CI = 1.000–1.029, p = 0.044). Following the second CCTA examination, major adverse cardiac events (MACEs) were observed in 12 patients, and NCL plaque progression was significantly associated with future MACEs (log rank p = 0.006). Noninvasive assessment of NCLs by CCTA has potential prognostic value.

  9. Growth of Necrotic Cores in Vulnerable Plaque

    Science.gov (United States)

    Fok, Pak-Wing

    2011-03-01

    Plaques are fatty deposits that grow mainly in arteries and develop as a result of a chronic inflammatory response. Plaques are called vulnerable when they are prone to mechanical rupture. Vulnerable Plaques (VPs) are characterized by lipid-rich, necrotic cores that are heavily infiltrated with macrophages. The rupture of VPs releases thrombogenic agents into the bloodstream, usually resulting in myocardial infarctions. We propose a quantitative model to predict the development of a plaque's necrotic core. By solving coupled reaction-diffusion equations for macrophages and dead cells, we explore the joint effects of hypoxic cell death and chemo-attraction to Ox-LDL, a molecule that is strongly linked to atherosclerosis. Our model predicts cores that have approximately the right size and shape. Normal mode analysis and subsequent calculation of the smallest eigenvalues allow us to compute the times required for the system to reach its steady state. This study allows us to make quantitative predictions for how quickly vulnerable plaques develop and how their growth depends on system parameters such as chemotactic coefficients and cell death rates.

  10. Functional Expression of Dental Plaque Microbiota

    Directory of Open Access Journals (Sweden)

    Scott Norman Peterson

    2014-08-01

    Full Text Available 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.

  11. Corneal plaque containing levofloxacin in a dog.

    Science.gov (United States)

    Park, Young-Woo; Kang, Byung-Jae; Lim, Jae Hyun; Ahn, Jung-Mo; Lim, Hyun Sook

    2015-11-01

    A 13-year-old castrated male Yorkshire terrier developed a corneal ulcer 2 weeks after intracapsular lens extraction (ICLE) in the right eye. The corneal ulcer was treated with levofloxacin eye drops. A plaque with a white luster developed in the central cornea 2 weeks after treatment with levofloxacin eye drops. The corneal plaque was surgically removed under inhalant anesthesia. The corneal plaque displayed antimicrobial activity against Escherichia coli. Furthermore, levofloxacin content in the plaque was confirmed by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight (MALDI-TOF/TOF) mass spectrometry (MS). The corneal ulcer completely resolved 2 weeks after the surgical removal of the corneal lesion and replacement of levofloxacin eye drops with tobramycin eye drops. Although the topical use of levofloxacin is unlikely to lead to corneal chemical deposits due to the high water solubility of the drug compared to other topical fluoroquinolones, this patient developed corneal plaque of the antibiotic drop. © 2015 American College of Veterinary Ophthalmologists.

  12. Functional expression of dental plaque microbiota.

    Science.gov (United States)

    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.

  13. Approach To Unstable Plaque In Carotid Disease

    Directory of Open Access Journals (Sweden)

    Mojdeh Ghabaee

    2017-02-01

    Full Text Available Risk of cerebral infarction due to thrombo emboli originating  from carotid artery disease estimated to be near 15%, and this risk  is closely associated with the severity of luminal stenosis. But at the same time characteristics  of the plaque should be taken into account for therapeutic planning when the patient is asymptomatic and the diameter of the stenosis does not reach the threshold of 70%. Search for markers of plaque vulnerability, instability, or thromboembolic potential as complementary to the degree of the luminal stenosis in stroke risk prediction should be considered .These morphologic features of carotid plaques are increasingly believed to be one of those markers that could carry further prognostic information, and early recognition of these plaques features may identify a high-risk subgroup of patients who might particularly benefit from aggressive interventions with aggressive medical treatment. Color and duplex Doppler sonography  evaluates both  morphologic and hemodynamic   abnormalitie of carotid. Echogensity, degree of stenosis and plaque surface features are essential parameters of morphological abnormality.

  14. The role of damage- and pathogen-associated molecular patterns in inflammation-mediated vulnerability of atherosclerotic plaques.

    Science.gov (United States)

    Rai, Vikrant; Agrawal, Devendra K

    2017-10-01

    Atherosclerosis is a chronic inflammatory disease resulting in the formation of the atherosclerotic plaque. Plaque formation starts with the inflammation in fatty streaks and progresses through atheroma, atheromatous plaque, and fibroatheroma leading to development of stable plaque. Hypercholesterolemia, dyslipidemia, and hyperglycemia are the risk factors for atherosclerosis. Inflammation, infection with viruses and bacteria, and dysregulation in the endothelial and vascular smooth muscle cells leads to advanced plaque formation. Death of the cells in the intima due to inflammation results in secretion of damage-associated molecular patterns (DAMPs) such as high mobility group box 1 (HMGB1), receptor for advanced glycation end products (RAGE), alarmins (S100A8, S100A9, S100A12, and oxidized low-density lipoproteins), and infection with pathogens leads to secretion of pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharides, lipoteichoic acids, and peptidoglycans. DAMPs and PAMPs further activate the inflammatory surface receptors such as TREM-1 and toll-like receptors and downstream signaling kinases and transcription factors leading to increased secretion of pro-inflammatory cytokines such as tumor necrosis factor α, interleukin (IL)-1β, IL-6, and interferon-γ and matrix metalloproteinases (MMPs). These mediators and cytokines along with MMPs render the plaque vulnerable for rupture leading to ischemic events. In this review, we have discussed the role of DAMPs and PAMPs in association with inflammation-mediated plaque vulnerability.

  15. Glial cell line-derived neurotrophic factor (GDNF) enhances sympathetic neurite growth in rat hearts at early developmental stages

    NARCIS (Netherlands)

    Miwa, Keiko; Lee, Jong-Kook; Takagishi, Yoshiko; Opthof, Tobias; Fu, Xianming; Kodama, Itsuo

    2010-01-01

    Molecular signaling of sympathetic innervation of myocardium is an unresolved issue. The purpose of this study was to investigate the effect of neurotrophic factors on sympathetic neurite growth towards cardiomyocytes. Cardiomyocytes (CMs) and sympathetic neurons (SNs) were isolated from neonatal

  16. Pituitary adenylate cyclase-activating peptide stimulates neurite growth in PC12 cells.

    Science.gov (United States)

    Hernandez, A; Kimball, B; Romanchuk, G; Mulholland, M W

    1995-01-01

    The ability of PACAP-38 to stimulate morphological development was studied using rat pheochromocytoma PC12 cells. PACAP-38 produced concentration-dependent increases in percentage of cells exhibiting neurite extension. Similar increases were produced by forskolin (28 +/- 2% at 96 h) and 8-bromo cAMP (30 +/- 2%). Vasoactive intestinal peptide and alpha-calcitonin gene-related peptide were without effect. PACAP-38 produced significant increases in PC12 cell cAMP content and inositol phosphate turnover. Intracellular [Ca2+] increased from 169 +/- 14 nM to 560 +/- 58 nM in response to 1 microM PACAP-38. PACAP-stimulated neurite outgrowth was abolished by RpcAMPS, an inhibitor of cAMP-dependent kinases but was unaffected by the protein kinase C antagonist H7.

  17. Large enhancement in neurite outgrowth on a cell membrane-mimicking conducting polymer

    Science.gov (United States)

    Zhu, Bo; Luo, Shyh-Chyang; Zhao, Haichao; Lin, Hsing-An; Sekine, Jun; Nakao, Aiko; Chen, Chi; Yamashita, Yoshiro; Yu, Hsiao-Hua

    2014-07-01

    Although electrically stimulated neurite outgrowth on bioelectronic devices is a promising means of nerve regeneration, immunogenic scar formation can insulate electrodes from targeted cells and tissues, thereby reducing the lifetime of the device. Ideally, an electrode material capable of electrically interfacing with neurons selectively and efficiently would be integrated without being recognized by the immune system and minimize its response. Here we develop a cell membrane-mimicking conducting polymer possessing several attractive features. This polymer displays high resistance towards nonspecific enzyme/cell binding and recognizes targeted cells specifically to allow intimate electrical communication over long periods of time. Its low electrical impedance relays electrical signals efficiently. This material is capable to integrate biochemical and electrical stimulation to promote neural cellular behaviour. Neurite outgrowth is enhanced greatly on this new conducting polymer; in addition, electrically stimulated secretion of proteins from primary Schwann cells can also occur on it.

  18. Terpenoids with neurite outgrowth-promoting activity from the branches and leaves of Illicium merrillianum.

    Science.gov (United States)

    Tian, Xin-Hui; Yue, Rong-Cai; Fang, Xin; Zhang, Jian-Ping; Wang, Guo-Wei; Shan, Lei; Zhang, Wei-Dong; Shen, Yun-Heng

    2016-05-01

    Eighteen terpenoids (1-18) were isolated from Illicium merrillianum. Compound 1 was identified as new compound, and its structure was established by comprehensive spectroscopic analysis and single-crystal X-ray diffraction. All compounds were evaluated for nerve growth factor (NGF)-mediated neurite outgrowth activity using rat pheochromocytoma (PC12) cells as a model system of neuronal differentiation. Compounds 1, 3, 18 showed significant neurite outgrowth-promoting activity in the presence of 20 ng/ml NGF in a dose-dependent manner at concentrations of 1-100 μM after 24-h treatment. Subtle difference of functional groups at C-2 position in hopane-type triterpene resulted in enormous bioactivity difference, compound 1 was neurotrophic but 2 was cytotoxic.

  19. Mechanisms involved in the regulation of neuropeptide-mediated neurite outgrowth: a minireview

    Directory of Open Access Journals (Sweden)

    Lestanova Z.

    2016-04-01

    Full Text Available The present knowledge, regarding the neuronal growth and neurite extension, includes neuropeptide action in the central nervous system. Research reports have brought much information about the multiple intracellular signaling pathways of neuropeptides. However, regardless of the differences in the local responses elicited by neuropeptides, there exist certain functional similarities in the effects of neuropeptides, mediated by their receptors. In the present review, data of the relevant studies, focused on G protein-coupled receptors activated by neuropeptides, are summarized. Particularly, receptors that activate phosphatidylinositol-calcium system and protein kinase C pathways, resulting in the reorganization of the neuronal cytoskeleton and changes in the neuronal morphology, are discussed. Based on our data received, we are showing that oxytocin increases the gene expression of GTPase cell division cycle protein 42 (Cdc42, implicated in many aspects of the neuronal growth and morphology. We are also paying a special attention to neurite extension and retraction in the context of neuropeptide regulation.

  20. Active Achilles tendon kinesitherapy accelerates Achilles tendon repair by promoting neurite regeneration☆

    Science.gov (United States)

    Jielile, Jiasharete; Aibai, Minawa; Sabirhazi, Gulnur; Shawutali, Nuerai; Tangkejie, Wulanbai; Badelhan, Aynaz; Nuerduola, Yeermike; Satewalede, Turde; Buranbai, Darehan; Hunapia, Beicen; Jialihasi, Ayidaer; Bai, Jingping; Kizaibek, Murat

    2012-01-01

    Active Achilles tendon kinesitherapy facilitates the functional recovery of a ruptured Achilles tendon. However, protein expression during the healing process remains a controversial issue. New Zealand rabbits, aged 14 weeks, underwent tenotomy followed immediately by Achilles tendon microsurgery to repair the Achilles tendon rupture. The tendon was then immobilized or subjected to postoperative early motion treatment (kinesitherapy). Mass spectrography results showed that after 14 days of motion treatment, 18 protein spots were differentially expressed, among which, 12 were up-regulated, consisting of gelsolin isoform b and neurite growth-related protein collapsing response mediator protein 2. Western blot analysis showed that gelsolin isoform b was up-regulated at days 7–21 of motion treatment. These findings suggest that active Achilles tendon kinesitherapy promotes the neurite regeneration of a ruptured Achilles tendon and gelsolin isoform b can be used as a biomarker for Achilles tendon healing after kinesitherapy. PMID:25317130

  1. Iron, Copper, and Zinc Concentration in Aβ Plaques in the APP/PS1 Mouse Model of Alzheimer's Disease Correlates with Metal Levels in the Surrounding Neuropil.

    Science.gov (United States)

    James, Simon A; Churches, Quentin I; de Jonge, Martin D; Birchall, Ian E; Streltsov, Victor; McColl, Gawain; Adlard, Paul A; Hare, Dominic J

    2017-03-15

    The metal ions of iron, copper, and zinc have long been associated with the aggregation of β-amyloid (Aβ) plaques in Alzheimer's disease; an interaction that has been suggested to promote increased oxidative stress and neuronal dysfunction. We examined plaque metal load in the hippocampus of APP/PS1 mice using X-ray fluorescence microscopy to assess how the anatomical location of Aβ plaques was influenced by the metal content of surrounding tissue. Immunohistochemical staining of Aβ plaques colocalized with areas of increased X-ray scattering power in unstained tissue sections, allowing direct X-ray based-assessment of plaque metal levels in sections subjected to minimal chemical fixation. We identified and mapped 48 individual plaques in four subregions of the hippocampus from four biological replicates. Iron, Cu, and Zn areal concentrations (ng cm-2) were increased in plaques compared to the surrounding neuropil. However, this elevation in metal load reflected the local metal makeup of the surrounding neuropil, where different brain regions are enriched for different metal ions. After correcting for tissue density, only Zn levels remained elevated in plaques. This study suggests that the in vivo binding of Zn to plaques is not simply due to increased protein deposition.

  2. Plaque rupture in humans and mice

    DEFF Research Database (Denmark)

    Schwartz, Stephen M; Galis, Zorina S; Rosenfeld, Michael E

    2007-01-01

    Despite the many studies of murine atherosclerosis, we do not yet know the relevance of the natural history of this model to the final events precipitated by plaque disruption of human atherosclerotic lesions. The literature has become particularly confused because of the common use of terms...... such as "instability", "vulnerable", "rupture", or even "thrombosis" for features of plaques in murine model systems not yet shown to rupture spontaneously and in an animal surprisingly resistant to formation of thrombi at sites of atherosclerosis. We suggest that use of conclusory terms like "vulnerable" and "stable...... that various forms of data have implicated in plaque progression. For example, formation of the fibrous cap, protease activation, and cell death in the necrotic core can be well described and have all been modeled in well-defined experiments. The relevance of such well-defined, objective, descriptive...

  3. Rewiring Neuronal Circuits: A New Method for Fast Neurite Extension and Functional Neuronal Connection.

    Science.gov (United States)

    Magdesian, Margaret H; Anthonisen, Madeleine; Lopez-Ayon, G Monserratt; Chua, Xue Ying; Rigby, Matthew; Grütter, Peter

    2017-06-13

    Brain and spinal cord injury may lead to permanent disability and death because it is still not possible to regenerate neurons over long distances and accurately reconnect them with an appropriate target. Here a procedure is described to rapidly initiate, elongate, and precisely connect new functional neuronal circuits over long distances. The extension rates achieved reach over 1.2 mm/h, 30-60 times faster than the in vivo rates of the fastest growing axons from the peripheral nervous system (0.02 to 0.04 mm/h)(28) and 10 times faster than previously reported for the same neuronal type at an earlier stage of development(4). First, isolated populations of rat hippocampal neurons are grown for 2-3 weeks in microfluidic devices to precisely position the cells, enabling easy micromanipulation and experimental reproducibility. Next, beads coated with poly-D-lysine (PDL) are placed on neurites to form adhesive contacts and pipette micromanipulation is used to move the resulting bead-neurite complex. As the bead is moved, it pulls out a new neurite that can be extended over hundreds of micrometers and functionally connected to a target cell in less than 1 h. This process enables experimental reproducibility and ease of manipulation while bypassing slower chemical strategies to induce neurite growth. Preliminary measurements presented here demonstrate a neuronal growth rate far exceeding physiological ones. Combining these innovations allows for the precise establishment of neuronal networks in culture with an unprecedented degree of control. It is a novel method that opens the door to a plethora of information and insights into signal transmission and communication within the neuronal network as well as being a playground in which to explore the limits of neuronal growth. The potential applications and experiments are widespread with direct implications for therapies that aim to reconnect neuronal circuits after trauma or in neurodegenerative diseases.

  4. Influence of micro-patterned PLLA membranes on outgrowth and orientation of hippocampal neurites.

    Science.gov (United States)

    Morelli, Sabrina; Salerno, Simona; Piscioneri, Antonella; Papenburg, Bernke J; Di Vito, Anna; Giusi, Giuseppina; Canonaco, Marcello; Stamatialis, Dimitrios; Drioli, Enrico; De Bartolo, Loredana

    2010-09-01

    In neuronal tissue engineering many efforts are focused on creating biomaterials with physical and chemical pathways for controlling cellular proliferation and orientation. Neurons have the ability to respond to topographical features in their microenvironment causing among others, axons to proliferate along surface features such as substrate grooves in micro-and nanoscales. As a consequence these neuronal elements are able to correctly adhere, migrate and orient within their new environment during growth. Here we explored the polarization and orientation of hippocampal neuronal cells on nonpatterned and micro-patterned biodegradable poly(l-lactic acid) (PLLA) membranes with highly selective permeable properties. Dense and porous nonpatterned and micro-patterned membranes were prepared from PLLA by Phase Separation Micromolding. The micro-patterned membranes have a three-dimensional structure consisting of channels and ridges and of bricks of different widths. Nonpatterned and patterned membranes were used for hippocampal neuronal cultures isolated from postnatal days 1-3 hamsters and the neurite length, orientation and specific functions of cells were investigated up to 12 days of culture. Neurite outgrowth, length plus orientation tightly overlapped the pattern of the membrane surface. Cell distribution occurred only in correspondence to membrane grooves characterized by continuous channels whereas on membranes with interconnected channels, cells not only adhered to and elongated their cellular processes in the grooves but also in the breaking points. High orientation degrees of cells were determined particularly on the patterned porous membranes with channel width of 20 mum and ridges of 17 mum whereas on dense nonpatterned membranes as well as on polystyrene culture dish (PSCD) controls, a larger number of primary developed neurites were distributed. Based on these results, PLLA patterned membranes may directly improve the guidance of neurite extension and

  5. NIR-responsive upconversion nanoparticles stimulate neurite outgrowth in PC12 cells.

    Science.gov (United States)

    Guan, Yijia; Li, Meng; Dong, Kai; Ren, Jinsong; Qu, Xiaogang

    2014-09-24

    Nerve regeneration is of diagnostic importance in neuroscience in regards to the treatment of degenerative disease. Owing to the ability to release rare-earth ions and produce ROS during upconversion process, upconversion nanoparticles are first reported for promoting neurite outgrowth. Different charged coating materials which play a critical role in cell attachment, can further lead to different effects on cell differentiation. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Ethanol-induced disruption of Golgi apparatus morphology, primary neurite number and cellular orientation in developing cortical neurons.

    Science.gov (United States)

    Powrozek, Teresa A; Olson, Eric C

    2012-11-01

    Prenatal ethanol exposure disrupts cortical neurite initiation and outgrowth, but prior studies have reported both ethanol-dependent growth promotion and inhibition. To resolve this ambiguity and better approximate in vivo conditions, we quantitatively analyzed neuronal morphology using a new, whole hemisphere explant model. In this model, Layer 6 (L6) cortical neurons migrate, laminate and extend neurites in an organotypic fashion. To selectively label L6 neurons, we performed ex utero electroporation of a GFP expression construct at embryonic day 13 and allowed the explants to develop for 2 days in vitro. Explants were exposed to (400 mg/dL) ethanol for either 4 or 24 h prior to fixation. Complete 3-D reconstructions were made of >80 GFP-positive neurons in each experimental condition. Acute responses to ethanol exposure included compaction of the Golgi apparatus accompanied by elaboration of supernumerary primary apical neurites, as well as a modest (∼15%) increase in higher order apical neurite length. With longer exposure time, ethanol exposure leads to a consistent, significant disorientation of the cell (cell body, primary apical neurite, and Golgi) with respect to the pial surface. The effects on cellular orientation were accompanied by decreased expression of cytoskeletal elements, microtubule-associated protein 2 and F-actin. These findings indicate that upon exposure to ethanol, developing L6 neurons manifest disruptions in Golgi apparatus and cytoskeletal elements which may in turn trigger selective and significant perturbations to primary neurite formation and neuronal polarity. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Cobalt60 plaques in recurrent retinoblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Fass, D.; McCormick, B.; Abramson, D.; Ellsworth, R. (Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, NY, NY (USA))

    1991-08-01

    Cobalt60 plaque irradiation is one treatment option for patients with recurrent retinoblastoma following conventional external beam irradiation (ERT). Tumorocidal doses can be delivered without excessive risk of normal tissue injury. In patients not considered candidates for xenon arc or cryotherapy, 60Co is an alternative to enucleation. Between 1968 and 1987, 85 patients were treated with 60Co plaques, 72 of whom had failed prior ERT. Age at diagnosis ranged from 1 week to 4 years. There are 37 males and 35 females. Seventy-one patients had bilateral disease and one had unilateral. Three patients had both eyes plaqued. Prior ERT ranged from 30 to 70 Gy (mean 4200 Gy). Time from initial therapy to failure ranged from 13 to 60 months. Cobalt plaques of 10 mm, 15 mm, or 10 {times} 15 mm were used depending on tumor size and location. Dose prescribed to the apex of the tumor ranged from 30 to 50 Gy (median 40 Gy) given over 3 to 8 days. Twelve patients had two plaque applications; three patients had three plaque applications. All patients were followed with routine ophthalmoscopic examinations. Follow-up ranged from 2 to 22 years (mean 8.7). Seven patients died of metastatic disease; 10 patients developed non-ocular second tumors. Thirty patients required enucleation. Twenty-two patients had clear tumor progression, two patients had radiation complications, and six patients had a combination of tumor growth and complications. Cobalt60 can salvage eyes in retinoblastoma patients failing ERT. Currently, the authors are using I125 in an attempt to spare normal ocular tissue and reduce subsequent complications.

  8. Directional neurite growth using carbon nanotube patterned substrates as a biomimetic cue

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Min Jee; Nam, Yoonkey [Department of Bio and Brain Engineering, KAIST, Daejeon (Korea, Republic of); Namgung, Seon; Hong, Seunghun, E-mail: seunghun@snu.ac.kr, E-mail: ynam@kaist.ac.kr [Department of Physics and Astronomy, Seoul National University, Seoul (Korea, Republic of)

    2010-06-11

    Researchers have made extensive efforts to mimic or reverse-engineer in vivo neural circuits using micropatterning technology. Various surface chemical cues or topographical structures have been proposed to design neuronal networks in vitro. In this paper, we propose a carbon nanotube (CNT)-based network engineering method which naturally mimics the structure of extracellular matrix (ECM). On CNT patterned substrates, poly-L-lysine (PLL) was coated, and E18 rat hippocampal neurons were cultured. In the early developmental stage, soma adhesion and neurite extension occurred in disregard of the surface CNT patterns. However, later the majority of neurites selectively grew along CNT patterns and extended further than other neurites that originally did not follow the patterns. Long-term cultured neuronal networks had a strong resemblance to the in vivo neural circuit structures. The selective guidance is possibly attributed to higher PLL adsorption on CNT patterns and the nanomesh structure of the CNT patterns. The results showed that CNT patterned substrates can be used as novel neuronal patterning substrates for in vitro neural engineering.

  9. A Wnt-Frz/Ror-Dsh pathway regulates neurite outgrowth in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Song Song

    2010-08-01

    Full Text Available One of the challenges to understand the organization of the nervous system has been to determine how axon guidance molecules govern axon outgrowth. Through an unbiased genetic screen, we identified a conserved Wnt pathway which is crucial for anterior-posterior (A/P outgrowth of neurites from RME head motor neurons in Caenorhabditis elegans. The pathway is composed of the Wnt ligand CWN-2, the Frizzled receptors CFZ-2 and MIG-1, the co-receptor CAM-1/Ror, and the downstream component Dishevelled/DSH-1. Among these, CWN-2 acts as a local attractive cue for neurite outgrowth, and its activity can be partially substituted with other Wnts, suggesting that spatial distribution plays a role in the functional specificity of Wnts. As a co-receptor, CAM-1 functions cell-autonomously in neurons and, together with CFZ-2 and MIG-1, transmits the Wnt signal to downstream effectors. Yeast two-hybrid screening identified DSH-1 as a binding partner for CAM-1, indicating that CAM-1 could facilitate CWN-2/Wnt signaling by its physical association with DSH-1. Our study reveals an important role of a Wnt-Frz/Ror-Dsh pathway in regulating neurite A/P outgrowth.

  10. Non-Obese Diabetic Mice Rapidly Develop Dramatic Sympathetic Neuritic Dystrophy

    Science.gov (United States)

    Schmidt, Robert E.; Dorsey, Denise A.; Beaudet, Lucie N.; Frederick, Kathy E.; Parvin, Curtis A.; Plurad, Santiago B.; Levisetti, Matteo G.

    2003-01-01

    To address the pathogenesis of diabetic autonomic neuropathy, we have examined the sympathetic nervous system in non-obese diabetic (NOD) and streptozotocin (STZ)-induced diabetic mice, two models of type 1 diabetes, and the db/db mouse, a model of type 2 diabetes. After only 3 to 5 weeks of diabetes, NOD mice developed markedly swollen axons and dendrites (“neuritic dystrophy”) in the prevertebral superior mesenteric and celiac ganglia (SMG-CG), similar to the pathology described in diabetic STZ- and BBW-rat and man. Comparable changes failed to develop in the superior cervical ganglia of the NOD mouse or in the SMG-CG of non-diabetic NOD siblings. STZ-induced diabetic mice develop identical changes, although at a much slower pace and to a lesser degree than NOD mice. NOD-SCID mice, which are genetically identical to NOD mice except for the absence of T and B cells, do not develop diabetes or neuropathology comparable to diabetic NOD mice. However, STZ-treated NOD-SCID mice develop severe neuritic dystrophy, evidence against an exclusively autoimmune pathogenesis for autonomic neuropathy in this model. Chronically diabetic type 2 db/db mice fail to develop neuritic dystrophy, suggesting that hyperglycemia alone may not be the critical and sufficient element. The NOD mouse appears to be a valuable model of diabetic sympathetic autonomic neuropathy with unambiguous, rapidly developing neuropathology which corresponds closely to the characteristic pathology of other rodent models and man. PMID:14578206

  11. Target deletion of the cytoskeleton-associated protein palladin does not impair neurite outgrowth in mice.

    Directory of Open Access Journals (Sweden)

    Run-Zhe Shu

    Full Text Available Palladin is an actin cytoskeleton-associated protein which is crucial for cell morphogenesis and motility. Previous studies have shown that palladin is localized to the axonal growth cone in neurons and may play an important role in axonal extension. Previously, we have generated palladin knockout mice which display cranial neural tube closure defect and embryonic lethality before embryonic day 15.5 (E15.5. To further study the role of palladin in the developing nervous system, we examined the innervation of palladin-deficient mouse embryos since the 200 kd, 140 kd, 90-92 kd and 50 kd palladin isoforms were undetectable in the mutant mouse embryo brain. Contrary to the results of previous studies, we found no inhibition of the axonal extension in palladin-deficient mouse embryos. The cortical neurons derived from palladin-deficient mice also showed no significant difference in neurite outgrowth as compared with those from wild-type mice. Moreover, no difference was found in neurite outgrowth of neural stem cell derived-neurons between palladin-deficient mice and wild-type mice. In conclusion, these results suggest that palladin is dispensable for normal neurite outgrowth in mice.

  12. LINGO-1 Interacts with WNK1 to Regulate Nogo-induced Inhibition of Neurite Extension*

    Science.gov (United States)

    Zhang, Zhaohuan; Xu, Xiaohui; Zhang, Yong; Zhou, Jianfeng; Yu, Zhongwang; He, Cheng

    2009-01-01

    LINGO-1 is a component of the tripartite receptor complexes, which act as a convergent mediator of the intracellular signaling in response to myelin-associated inhibitors and lead to collapse of growth cone and inhibition of neurite extension. Although the function of LINGO-1 has been intensively studied, its downstream signaling remains elusive. In the present study, a novel interaction between LINGO-1 and a serine-threonine kinase WNK1 was identified by yeast two-hybrid screen. The interaction was further validated by fluorescence resonance energy transfer and co-immunoprecipitation, and this interaction was intensified by Nogo66 treatment. Morphological evidences showed that WNK1 and LINGO-1 were co-localized in cortical neurons. Furthermore, either suppressing WNK1 expression by RNA interference or overexpression of WNK1-(123–510) attenuated Nogo66-induced inhibition of neurite extension and inhibited the activation of RhoA. Moreover, WNK1 was identified to interact with Rho-GDI1, and this interaction was attenuated by Nogo66 treatment, further indicating its regulatory effect on RhoA activation. Taken together, our results suggest that WNK1 is a novel signaling molecule involved in regulation of LINGO-1 mediated inhibition of neurite extension. PMID:19363035

  13. LINGO-1 interacts with WNK1 to regulate nogo-induced inhibition of neurite extension.

    Science.gov (United States)

    Zhang, Zhaohuan; Xu, Xiaohui; Zhang, Yong; Zhou, Jianfeng; Yu, Zhongwang; He, Cheng

    2009-06-05

    LINGO-1 is a component of the tripartite receptor complexes, which act as a convergent mediator of the intracellular signaling in response to myelin-associated inhibitors and lead to collapse of growth cone and inhibition of neurite extension. Although the function of LINGO-1 has been intensively studied, its downstream signaling remains elusive. In the present study, a novel interaction between LINGO-1 and a serine-threonine kinase WNK1 was identified by yeast two-hybrid screen. The interaction was further validated by fluorescence resonance energy transfer and co-immunoprecipitation, and this interaction was intensified by Nogo66 treatment. Morphological evidences showed that WNK1 and LINGO-1 were co-localized in cortical neurons. Furthermore, either suppressing WNK1 expression by RNA interference or overexpression of WNK1-(123-510) attenuated Nogo66-induced inhibition of neurite extension and inhibited the activation of RhoA. Moreover, WNK1 was identified to interact with Rho-GDI1, and this interaction was attenuated by Nogo66 treatment, further indicating its regulatory effect on RhoA activation. Taken together, our results suggest that WNK1 is a novel signaling molecule involved in regulation of LINGO-1 mediated inhibition of neurite extension.

  14. Dobesilate in the treatment of plaque psoriasis.

    Science.gov (United States)

    Cuevas, Pedro; Arrazola, Jose M

    2005-09-12

    Fibroblast growth factor (FGF)-mediated pathways participate in many of the cellular events implicated in the pathogenesis of psoriasis. Thus, targeting FGF signals may be potentially therapeutic in the treatment of psoriasis. We report for the first time on a 43-year-old man with chronic-type plaque psoriasis with a daily topical treatment of dobesilate, a new FGF inhibitor. As early as at day 14, the patient had cleared or achieved excellent improvement of psoriatic skin lesions. Topical dobesilate offers the potential for treatment of plaque psoriasis without atrophy or other local side effects associated with the use of topical corticosteroids.

  15. A modified COMS plaque for iris melanoma

    Directory of Open Access Journals (Sweden)

    Daniel J. Scanderbeg

    2011-09-01

    Full Text Available Melanoma of the iris is a rare condition compared to posterior ocular tumors and in this case report we presenta 51-year-old female patient with diffuse iris melanoma. Traditional COMS (Collaborative Ocular Melanoma Studyplaques are used at our institution for radiation therapy, so a novel modification of the traditional plaque was requiredto allow better conformance with placement on the cornea. The usual silastic insert was machined to dimensions incompliance with the cornea, placed without incident, and treatment delivered with excellent patient tolerance of themodified plaque.

  16. Effectiveness of Electric Toothbrushes on Plaque Removal

    OpenAIRE

    佐藤, 悦子; 高見沢, 恵; 奥田, 一博; 原, 耕二; 新井, 文子; 藤野, 仁; Satoh, Etsuko; Takamizawa, Megumi; Okuda, Kazuhiro; Hara, Kohji; Arai, Humiko; Fujino, Hitoshi

    1992-01-01

    The purpose of this study was to compare the plaque removal efficiency of two types of toothbrushes, one with a rotary combined with horizontal movement (brush 1) and the other with a rotary movement (brush 2) on 13 volunteers. They stopped all oral hygiene procedures for 48 houres, after which the subjects were instructed to brush their teeth for two minutes with each of the respective electric toothbrushes using the split-mouth technique twice a day and continued to brush for 1week. Plaque ...

  17. Robust neurite extension following exogenous electrical stimulation within single walled carbon nanotube-composite hydrogels.

    Science.gov (United States)

    Koppes, A N; Keating, K W; McGregor, A L; Koppes, R A; Kearns, K R; Ziemba, A M; McKay, C A; Zuidema, J M; Rivet, C J; Gilbert, R J; Thompson, D M

    2016-07-15

    The use of exogenous electrical stimulation to promote nerve regeneration has achieved only limited success. Conditions impeding optimized outgrowth may arise from inadequate stimulus presentation due to differences in injury geometry or signal attenuation. Implantation of an electrically-conductive biomaterial may mitigate this attenuation and provide a more reproducible signal. In this study, a conductive nanofiller (single-walled carbon nanotubes [SWCNT]) was selected as one possible material to manipulate the bulk electrical properties of a collagen type I-10% Matrigel™ composite hydrogel. Neurite outgrowth within hydrogels (SWCNT or nanofiller-free controls) was characterized to determine if: (1) nanofillers influence neurite extension and (2) electrical stimulation of the nanofiller composite hydrogel enhances neurite outgrowth. Increased SWCNT loading (10-100-μg/mL) resulted in greater bulk conductivity (up to 1.7-fold) with no significant changes to elastic modulus. Neurite outgrowth increased 3.3-fold in 20-μg/mL SWCNT loaded biomaterials relative to the nanofiller-free control. Electrical stimulation promoted greater outgrowth (2.9-fold) within SWCNT-free control. The concurrent presentation of electrical stimulation and SWCNT-loaded biomaterials resulted in a 7.0-fold increase in outgrowth relative to the unstimulated, nanofiller-free controls. Local glia residing within the DRG likely contribute, in part, to the observed increases in outgrowth; but it is unknown which specific nanofiller properties influence neurite extension. Characterization of neuronal behavior in model systems, such as those described here, will aid the rational development of biomaterials as well as the appropriate delivery of electrical stimuli to support nerve repair. Novel biomedical devices delivering electrical stimulation are being developed to mitigate symptoms of Parkinson's, treat drug-resistant depression, control movement or enhance verve regeneration. Carbon

  18. is plaque removal efficacy of toothbrush related to bristle flaring?

    African Journals Online (AJOL)

    GB

    2013-11-03

    Nov 3, 2013 ... subsequently they brought the habit back home which gave momentum for ... of microbial plaque on teeth and supporting .... plaque assessment, the toothbrushes were ..... toothbrush (23,24) decreasing the functional ability of ...

  19. The clinical value of histological femoral artery plaque analysis

    NARCIS (Netherlands)

    Derksen, W.J.M.

    2011-01-01

    This thesis showed that the dissected femoral atherosclerotic plaque contains a predictive value for clinical outcome after femoral endarterectomy. Plaque histology analysis should be incorporated in clinical practice to help predict the patient at risk for restenosis or secondary cardiovascular

  20. Image Analysis for Contrast Enhanced Ultrasound Carotid Plaque Imaging

    NARCIS (Netherlands)

    Z. Akkus (Zeynettin)

    2014-01-01

    markdownabstract__Abstract__ Intraplaque neovascularization (IPN) has been presented as an important biomarker for progressive atherosclerotic disease and plaque vulnerability in several pathological studies. Therefore, quantification of IPN may allow early prediction of plaque at risk of rupture

  1. Modulography: elasticity imaging of atherosclerotic plaques

    NARCIS (Netherlands)

    R. Baldewsing (Radj)

    2006-01-01

    textabstractModulography is an experimental elasticity imaging method. It has potential to become an all-in-one in vivo tool (a) for detecting vulnerable atherosclerotic coronary plaques, (b) for assessing information related to their rupture-proneness and (c) for imaging their elastic material

  2. Vaporization of atherosclerotic plaques by spark erosion

    NARCIS (Netherlands)

    C.J. Slager (Cornelis); C.E. Essed; J.C.H. Schuurbiers (Johan); N. Bom (Klaas); P.W.J.C. Serruys (Patrick); G.T. Meester (Geert)

    1985-01-01

    textabstractAn alternative to the laser irradiation of atherosclerotic lesions has been developed. A pulsed electrocardiogram R wave-triggered electrical spark erosion technique is described. Controlled vaporization of fibrous and lipid plaques with minimal thermal side effects was achieved and

  3. The high-risk plaque initiative

    DEFF Research Database (Denmark)

    Falk, Erling; Sillesen, Henrik; Muntendam, Pieter

    2011-01-01

    The High-Risk Plaque (HRP) Initiative is a research and development effort to advance the understanding, recognition, and management of asymptomatic individuals at risk for a near-term atherothrombotic event such as myocardial infarction or stroke. Clinical studies using the newest technologies...

  4. Intracoronary Thermography: a vulnerable Plaque Detection Technique?

    NARCIS (Netherlands)

    A.G. ten Have (Anna)

    2006-01-01

    textabstractThe studies reported in this thesis were performed to answer the central question: can intracoronary thermography be used for vulnerable plaque detection? To answer this question, we have identified parameters that influence intracoronary thermography measurements, and have studied to

  5. 3.0 T plaque imaging.

    Science.gov (United States)

    Hinton-Yates, Denise P; Cury, Ricardo C; Wald, Lawrence L; Wiggins, Graham C; Keil, Boris; Seethmaraju, Ravi; Gangadharamurthy, Dakshinamurthy; Ogilvy, Christopher S; Dai, Guangping; Houser, Stuart L; Stone, James R; Furie, Karen L

    2007-10-01

    The aim of this article is to evaluate 3.0 T magnetic resonance imaging for characterization of vessel morphology and plaque composition. Emphasis is placed on early and moderate stages of carotid atherosclerosis, where increases in signal-to-noise (SNR) and contrast-to-noise (CNR) ratios compared with 1.5 T are sought. Comparison of in vivo 3.0 T imaging to histopathology is performed for validation. Parallel acceleration methods applied with an 8-channel carotid array are investigated as well as higher field ex vivo imaging to explore even further gains. The overall endeavor is to improve prospective assessment of atherosclerosis stage and stability for reduction of atherothrombotic event risk. A total of 10 male and female subjects ranging in age from 22 to 72 years (5 healthy and 5 with cardiovascular disease) participated. Custom-built array coils were used with endogenous and exogenous multicontrast bright and black-blood protocols for 3.0 T carotid imaging. Comparisons were performed to 1.5 T, and ex vivo plaque was stained with hematoxylin and eosin for histology. Imaging (9.4 T) was also performed on intact specimens. The factor of 2 gain in signal-to-noise SNR is realized compared with 1.5 T along with improved wall-lumen and plaque component CNR. Post-contrast black-blood imaging within 5-10 minutes of gadolinium injection is optimal for detection of the necrotic lipid component. In a preliminary 18-month follow-up study, this method provided measurement of a 50% reduction in lipid content with minimal change in plaque size in a subject receiving aggressive statin therapy. Parallel imaging applied with signal averaging further improves 3.0 T black-blood vessel wall imaging. The use of 3.0 T for carotid plaque imaging has demonstrated increases in SNR and CNR compared with 1.5 T. Quantitative prospective studies of moderate and early plaques are feasible at 3.0 T. Continued improvements in coil arrays, 3-dimensional pulse sequences, and the use of novel

  6. Tensile and compressive properties of fresh human carotid atherosclerotic plaques.

    LENUS (Irish Health Repository)

    Maher, Eoghan

    2009-12-11

    Accurate characterisation of the mechanical properties of human atherosclerotic plaque is important for our understanding of the role of vascular mechanics in the development and treatment of atherosclerosis. The majority of previous studies investigating the mechanical properties of human plaque are based on tests of plaque tissue removed following autopsy. This study aims to characterise the mechanical behaviour of fresh human carotid plaques removed during endarterectomy and tested within 2h. A total of 50 radial compressive and 17 circumferential tensile uniaxial tests were performed on samples taken from 14 carotid plaques. The clinical classification of each plaque, as determined by duplex ultrasound is also reported. Plaques were classified as calcified, mixed or echolucent. Experimental data indicated that plaques were highly inhomogeneous; with variations seen in the mechanical properties of plaque obtained from individual donors and between donors. The mean behaviour of samples for each classification indicated that calcified plaques had the stiffest response, while echolucent plaques were the least stiff. Results also indicated that there may be a difference in behaviour of samples taken from different anatomical locations (common, internal and external carotid), however the large variability indicates that more testing is needed to reach significant conclusions. This work represents a step towards a better understanding of the in vivo mechanical behaviour of human atherosclerotic plaque.

  7. Review: Mechanical Characterization of Carotid Arteries and Atherosclerotic Plaques

    NARCIS (Netherlands)

    Korte, C.L. de; Fekkes, S.; Nederveen, A.J.; Manniesing, R.; Hansen, H.R.

    2016-01-01

    Cardiovascular disease (CVD) is a leading cause of death and is in the majority of cases due to the formation of atherosclerotic plaques in arteries. Initially, thickening of the inner layer of the arterial wall occurs. Continuation of this process leads to plaque formation. The risk of a plaque to

  8. Detection of six novel papillomavirus sequences within canine pigmented plaques

    Science.gov (United States)

    Luff, Jennifer A.; Affolter, Verena K.; Yeargan, Bret; Moore, Peter F.

    2013-01-01

    In dogs, papillomaviruses are thought to cause oral and cutaneous papillomas and pigmented plaques. Eight canine papillomaviruses have been fully sequenced to date. Four of these canine papillomaviruses, including Canis familiaris papillomavirus (CPV)-3, CPV-4, CPV-5, and CPV-8, were amplified from pigmented plaques. Given this recent identification of several different canine papillomaviruses within pigmented plaques, it is likely that there are additional papillomavirus sequences that have not been previously identified. The aim of this study was to detect papillomavirus DNA sequences from pigmented plaques and identify potentially novel PV sequences through nucleotide sequence analysis. Polymerase chain reaction was used to amplify DNA sequences of the papillomavirus L1 gene from 27 pigmented plaques. Identification of novel papillomavirus sequences was based upon less than 90% shared DNA homology to any known papillomavirus. Ten different papillomaviruses were detected within the pigmented plaques, including 6 novel PV sequences. CPV-4 was detected within 41% (11/27) of the pigmented plaques, while CPV-5 was identified within 2 pigmented plaques and CPV-3 within a single pigmented plaque. A previously identified novel papillomavirus sequence was identified within 2 pigmented plaques in this study. The remaining 11 pigmented plaques contained 6 papillomavirus DNA sequences that have not been previously reported. These novel PV sequences were most similar to papillomaviruses that have been detected within canine pigmented plaques. PMID:22529129

  9. Determining carotid plaque vulnerability using ultrasound center frequency shifts.

    Science.gov (United States)

    Erlöv, Tobias; Cinthio, Magnus; Edsfeldt, Andreas; Segstedt, Simon; Dias, Nuno; Nilsson, Jan; Gonçalves, Isabel

    2016-03-01

    The leading cause of morbidity and mortality worldwide is atherosclerotic cardiovascular disease, most commonly caused by rupture of a high-risk plaque and subsequent thrombosis resulting in stroke, myocardial infarction or sudden death depending on the affected arterial territory. Accurate, non-invasive methods to identify such lesions known as vulnerable or high-risk plaques are currently sub-optimal. Our aim was to validate a new non-invasive ultrasound method to identify high-risk carotid plaques. We evaluated a new method based on the center frequency shift (CFS) of the ultrasound radio frequency data obtained from carotid plaques compared to a reference phantom. We evaluated the method both ex vivo, on 157 sections from 18 plaques, and in vivo, in 39 patients 1-day prior to carotid plaque removal, and correlated the data with histology. The CFS correlated with a plaque vulnerability index based on histological areas stained for lipids, macrophages, hemorrhage, smooth muscle cells and collagen (r = -0.726, P = 1.7 × 10(-8)). Plaques with CFS below median had larger cores, more macrophages and were less rich in collagen in agreement with the definition of rupture-prone plaques. The accuracy to detect plaques with high vulnerability index was 78% (confidence interval (CI) 61-89%), with sensitivity 77% (CI 61-89%) and specificity 78% (CI 62-89%). Our method is the first to characterize atherosclerotic plaque components that affect plaque vulnerability using CFS. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Animal models for plaque rupture: a biomechanical assessment

    NARCIS (Netherlands)

    van der Heiden, Kim; Hoogendoorn, Ayla; Daemen, Mat J.; Gijsen, Frank J. H.

    2016-01-01

    Rupture of atherosclerotic plaques is the main cause of acute cardiovascular events. Animal models of plaque rupture are rare but essential for testing new imaging modalities to enable diagnosis of the patient at risk. Moreover, they enable the design of new treatment strategies to prevent plaque

  11. Inhibitory effects of brain-derived neurotrophic factor precursor on viability and neurite growth of murine hippocampal neurons

    Directory of Open Access Journals (Sweden)

    Jia CHEN

    2014-10-01

    Full Text Available Objective To explore the mediation effect of p75 neurotrophin receptor (p75NTR in the effect of brainderived neurotrophic factor precursor (proBDNF on viability and neurite growth of murine hippocampal neurons. Methods  Hippocampal neurons were obtained from p75NTR+/+ and p75NTR-/- 18-day mice and primarily cultured. For p75NTR+/+ neurons, three experimental groups were set, i.e. control, proBDNF (30ng/ml, and proBDNF (30ng/ml+p75/Fc (30µg/ml groups. For p75NTR-/- neurons, two experimental groups were set, i.e. control and proBDNF (30ng/ml groups. MTT assays were performed after 24h to examine the viability of neonatal primary neurons. Immunofluorescent staining was conducted after 72h to investigate the neurite length. Results With MAP2 and DAPI double fluorescent staining it was identified that the neonatal hippocampal neurons were successfully cultured in vitro with high purity. For viability assay of p75NTR+/+ neurons, it was found that the absorbance value at 570nm (A570 in proBDNF group was significantly lower than that in control group (P0.05. With neurite growth assay of p75NTR+/+ neurons, it was found that the neurite length in proBDNF group was significantly shorter than that in control group (P0.05. With neurite growth assay of p75NTR-/- neurons, no difference in neurite length was observed between proBDNF group and control group. Conclusion proBDNF may inhibit the neuronal viability and neurite growth via p75NTR. DOI: 10.11855/j.issn.0577-7402.2014.09.03

  12. Enhanced neurite outgrowth of human model (NT2) neurons by small-molecule inhibitors of Rho/ROCK signaling.

    Science.gov (United States)

    Roloff, Frank; Scheiblich, Hannah; Dewitz, Carola; Dempewolf, Silke; Stern, Michael; Bicker, Gerd

    2015-01-01

    Axonal injury in the adult human central nervous system often results in loss of sensation and motor functions. Promoting regeneration of severed axons requires the inactivation of growth inhibitory influences from the tissue environment and stimulation of the neuron intrinsic growth potential. Especially glial cell derived factors, such as chondroitin sulfate proteoglycans, Nogo-A, myelin-associated glycoprotein, and myelin in general, prevent axon regeneration. Most of the glial growth inhibiting factors converge onto the Rho/ROCK signaling pathway in neurons. Although conditions in the injured nervous system are clearly different from those during neurite outgrowth in vitro, here we use a chemical approach to manipulate Rho/ROCK signalling with small-molecule agents to encourage neurite outgrowth in cell culture. The development of therapeutic treatments requires drug testing not only on neurons of experimental animals, but also on human neurons. Using human NT2 model neurons, we demonstrate that the pain reliever Ibuprofen decreases RhoA (Ras homolog gene family, member A GTPase) activation and promotes neurite growth. Inhibition of the downstream effector Rho kinase by the drug Y-27632 results in a strong increase in neurite outgrowth. Conversely, activation of the Rho pathway by lysophosphatidic acid results in growth cone collapse and eventually to neurite retraction. Finally, we show that blocking of Rho kinase, but not RhoA results in an increase in neurons bearing neurites. Due to its anti-inflammatory and neurite growth promoting action, the use of a pharmacological treatment of damaged neural tissue with Ibuprofen should be explored.

  13. Enhanced neurite outgrowth of human model (NT2 neurons by small-molecule inhibitors of Rho/ROCK signaling.

    Directory of Open Access Journals (Sweden)

    Frank Roloff

    Full Text Available Axonal injury in the adult human central nervous system often results in loss of sensation and motor functions. Promoting regeneration of severed axons requires the inactivation of growth inhibitory influences from the tissue environment and stimulation of the neuron intrinsic growth potential. Especially glial cell derived factors, such as chondroitin sulfate proteoglycans, Nogo-A, myelin-associated glycoprotein, and myelin in general, prevent axon regeneration. Most of the glial growth inhibiting factors converge onto the Rho/ROCK signaling pathway in neurons. Although conditions in the injured nervous system are clearly different from those during neurite outgrowth in vitro, here we use a chemical approach to manipulate Rho/ROCK signalling with small-molecule agents to encourage neurite outgrowth in cell culture. The development of therapeutic treatments requires drug testing not only on neurons of experimental animals, but also on human neurons. Using human NT2 model neurons, we demonstrate that the pain reliever Ibuprofen decreases RhoA (Ras homolog gene family, member A GTPase activation and promotes neurite growth. Inhibition of the downstream effector Rho kinase by the drug Y-27632 results in a strong increase in neurite outgrowth. Conversely, activation of the Rho pathway by lysophosphatidic acid results in growth cone collapse and eventually to neurite retraction. Finally, we show that blocking of Rho kinase, but not RhoA results in an increase in neurons bearing neurites. Due to its anti-inflammatory and neurite growth promoting action, the use of a pharmacological treatment of damaged neural tissue with Ibuprofen should be explored.

  14. Ginsenoside-Rd Promotes Neurite Outgrowth of PC12 Cells through MAPK/ERK- and PI3K/AKT-Dependent Pathways.

    Science.gov (United States)

    Wu, Song-Di; Xia, Feng; Lin, Xue-Mei; Duan, Kang-Li; Wang, Fang; Lu, Qing-Li; Cao, Huan; Qian, Yi-Hua; Shi, Ming

    2016-01-29

    Panax ginseng is a famous herbal medicine widely used in Asia. Ginsenosides have been identified as the principle active ingredients for Panax ginseng's biological activity, among which ginsenoside Rd (Rd) attracts extensive attention for its obvious neuroprotective activities. Here we investigated the effect of Rd on neurite outgrowth, a crucial process associated with neuronal repair. PC12 cells, which respond to nerve growth factor (NGF) and serve as a model for neuronal cells, were treated with different concentrations of Rd, and then their neurite outgrowth was evaluated. Our results showed that 10 μM Rd significantly increased the percentages of long neurite- and branching neurite-bearing cells, compared with respective controls. The length of the longest neurites and the total length of neurites in Rd-treated PC12 cells were much longer than that of respective controls. We also showed that Rd activated ERK1/2 and AKT but not PKC signalings, and inhibition of ERK1/2 by PD98059 or/and AKT by LY294002 effectively attenuated Rd-induced neurite outgrowth. Moreover, Rd upregulated the expression of GAP-43, a neuron-specific protein involved in neurite outgrowth, while PD98059 or/and LY294002 decreased Rd-induced increased GAP-43 expression. Taken together, our results provided the first evidence that Rd may promote the neurite outgrowth of PC12 cells by upregulating GAP-43 expression via ERK- and ARK-dependent signaling pathways.

  15. Topographic association of angioscopic yellow plaques with coronary atherosclerotic plaque: assessment with quantitative colorimetry in human coronary artery autopsy specimens.

    Science.gov (United States)

    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 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.

  16. Cannabinoid CB2 Receptors and Fatty Acid Amide Hydrolase Are Selectively Overexpressed in Neuritic Plaque-Associated Glia in Alzheimer's Disease Brains

    National Research Council Canada - National Science Library

    Benito, Cristina; Nunez, Estefania; Tolon, Rosa M; Carrier, Erica J; Rabano, Alberto; Hillard, Cecilia J; Romero, Julian

    2003-01-01

    .... We have studied the status of some of the components of the endocannabinoid system, fatty acid amide hydrolase and cannabinoid CB1 and CB2 receptors, in postmortem brains from patients with Alzheimer's disease...

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

    Science.gov (United States)

    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.

  18. Sialylation of neurites inhibits complement-mediated macrophage removal in a human macrophage-neuron co-culture system

    Science.gov (United States)

    Linnartz-Gerlach, Bettina; Schuy, Christine; Shahraz, Anahita; Tenner, Andrea J.; Neumann, Harald

    2015-01-01

    The complement system has been implicated in the removal of dysfunctional synapses and neurites during development and in disease processes in the mouse, but it is unclear how far the mouse data can be transferred to humans. Here, we co-cultured macrophages derived from human THP1 monocytes and neurons derived from human induced pluripotent stem cells, to study the role of the complement system in a human model. Components of the complement system were expressed by the human macrophages and human neuronal culture, while receptors of the complement cascade were expressed by human macrophages as shown via gene transcript analysis and flow cytometry. We mimicked pathological conditions leading to an altered glycocalyx by treatment of human neurons with sialidases. Desialylated human neurites were opsonized by the complement component C1q. Furthermore, human neurites with an intact sialic acid cap remained untouched, while desialylated human neurites were removed and ingested by human macrophages. While blockage of the complement receptor 1 (CD35) had no effect, blockage of CD11b as part of the complement receptor 3 (CR3) reversed the effect on macrophage phagocytosis of desialylated human neurites. Data demonstrate that in the human system sialylation of the neuronal glycocalyx serves as an inhibitory flag for complement binding and CR3 mediated phagocytosis by macrophages. PMID:26257016

  19. μ2-Dependent endocytosis of N-cadherin is regulated by β-catenin to facilitate neurite outgrowth.

    Science.gov (United States)

    Chen, Yi-Ting; Tai, Chin-Yin

    2017-05-01

    Circuit formation in the brain requires neurite outgrowth throughout development to establish synaptic contacts with target cells. Active endocytosis of several adhesion molecules facilitates the dynamic exchange of these molecules at the surface and promotes neurite outgrowth in developing neurons. The endocytosis of N-cadherin, a calcium-dependent adhesion molecule, has been implicated in the regulation of neurite outgrowth, but the mechanism remains unclear. Here, we identified that a fraction of N-cadherin internalizes through clathrin-mediated endocytosis (CME). Two tyrosine-based motifs in the cytoplasmic domain of N-cadherin recognized by the μ2 subunit of the AP-2 adaptor complex are responsible for CME of N-cadherin. Moreover, β-catenin, a core component of the N-cadherin adhesion complex, inhibits N-cadherin endocytosis by masking the 2 tyrosine-based motifs. Removal of β-catenin facilitates μ2 binding to N-cadherin, thereby increasing clathrin-mediated N-cadherin endocytosis and neurite outgrowth without affecting the steady-state level of surface N-cadherin. These results identify and characterize the mechanism controlling N-cadherin endocytosis through β-catenin-regulated μ2 binding to modulate neurite outgrowth. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Low-frequency dielectric dispersion of brain tissue due to electrically long neurites

    Science.gov (United States)

    Monai, Hiromu; Inoue, Masashi; Miyakawa, Hiroyoshi; Aonishi, Toru

    2012-12-01

    The dielectric properties of brain tissue are important for understanding how neural activity is related to local field potentials and electroencephalograms. It is known that the permittivity of brain tissue exhibits strong frequency dependence (dispersion) and that the permittivity is very large in the low-frequency region. However, little is known with regard to the cause of the large permittivity in the low-frequency region. Here, we postulate that the dielectric properties of brain tissue can be partially accounted for by assuming that neurites are of sufficient length to be “electrically long.” To test this idea, we consider a model in which a neurite is treated as a long, narrow body, and it is subjected to a stimulus created by electrodes situated in the region external to it. With regard to this electric stimulus, the neurite can be treated as a passive cable. Assuming adequate symmetry so that the tissue packed with multiple cables is equivalent to an isolated system consisting of a single cable and a surrounding extracellular resistive medium, we analytically calculate the extracellular potential of the tissue in response to such an externally created alternating-current electric field using a Green's function that we obtained previously. Our results show that brain tissue modeled by such a cable existing within a purely resistive extracellular medium exhibits a large effective permittivity in the low-frequency region. Moreover, we obtain results suggesting that an extremely large low-frequency permittivity can coexist with weak low-pass filter characteristics in brain tissue.

  1. Exposure to 1800 MHz radiofrequency radiation impairs neurite outgrowth of embryonic neural stem cells

    Science.gov (United States)

    Chen, Chunhai; Ma, Qinlong; Liu, Chuan; Deng, Ping; Zhu, Gang; Zhang, Lei; He, Mindi; Lu, Yonghui; Duan, Weixia; Pei, Liping; Li, Min; Yu, Zhengping; Zhou, Zhou

    2014-01-01

    A radiofrequency electromagnetic field (RF-EMF) of 1800 MHz is widely used in mobile communications. However, the effects of RF-EMFs on cell biology are unclear. Embryonic neural stem cells (eNSCs) play a critical role in brain development. Thus, detecting the effects of RF-EMF on eNSCs is important for exploring the effects of RF-EMF on brain development. Here, we exposed eNSCs to 1800 MHz RF-EMF at specific absorption rate (SAR) values of 1, 2, and 4 W/kg for 1, 2, and 3 days. We found that 1800 MHz RF-EMF exposure did not influence eNSC apoptosis, proliferation, cell cycle or the mRNA expressions of related genes. RF-EMF exposure also did not alter the ratio of eNSC differentiated neurons and astrocytes. However, neurite outgrowth of eNSC differentiated neurons was inhibited after 4 W/kg RF-EMF exposure for 3 days. Additionally, the mRNA and protein expression of the proneural genes Ngn1 and NeuroD, which are crucial for neurite outgrowth, were decreased after RF-EMF exposure. The expression of their inhibitor Hes1 was upregulated by RF-EMF exposure. These results together suggested that 1800 MHz RF-EMF exposure impairs neurite outgrowth of eNSCs. More attention should be given to the potential adverse effects of RF-EMF exposure on brain development. PMID:24869783

  2. Exposure to 1800 MHz radiofrequency radiation impairs neurite outgrowth of embryonic neural stem cells.

    Science.gov (United States)

    Chen, Chunhai; Ma, Qinlong; Liu, Chuan; Deng, Ping; Zhu, Gang; Zhang, Lei; He, Mindi; Lu, Yonghui; Duan, Weixia; Pei, Liping; Li, Min; Yu, Zhengping; Zhou, Zhou

    2014-05-29

    A radiofrequency electromagnetic field (RF-EMF) of 1800 MHz is widely used in mobile communications. However, the effects of RF-EMFs on cell biology are unclear. Embryonic neural stem cells (eNSCs) play a critical role in brain development. Thus, detecting the effects of RF-EMF on eNSCs is important for exploring the effects of RF-EMF on brain development. Here, we exposed eNSCs to 1800 MHz RF-EMF at specific absorption rate (SAR) values of 1, 2, and 4 W/kg for 1, 2, and 3 days. We found that 1800 MHz RF-EMF exposure did not influence eNSC apoptosis, proliferation, cell cycle or the mRNA expressions of related genes. RF-EMF exposure also did not alter the ratio of eNSC differentiated neurons and astrocytes. However, neurite outgrowth of eNSC differentiated neurons was inhibited after 4 W/kg RF-EMF exposure for 3 days. Additionally, the mRNA and protein expression of the proneural genes Ngn1 and NeuroD, which are crucial for neurite outgrowth, were decreased after RF-EMF exposure. The expression of their inhibitor Hes1 was upregulated by RF-EMF exposure. These results together suggested that 1800 MHz RF-EMF exposure impairs neurite outgrowth of eNSCs. More attention should be given to the potential adverse effects of RF-EMF exposure on brain development.

  3. β-Hydroxy-β-Methylbutyrate (HMB Promotes Neurite Outgrowth in Neuro2a Cells.

    Directory of Open Access Journals (Sweden)

    Rafael Salto

    Full Text Available β-Hydroxy-β-methylbutyrate (HMB has been shown to enhance cell survival, differentiation and protein turnover in muscle, mainly activating phosphoinositide-3-kinase/protein kinase B (PI3K/Akt and mitogen-activated protein kinases/ extracellular-signal-regulated kinases (MAPK/ERK signaling pathways. Since these two pathways are related to neuronal survival and differentiation, in this study, we have investigated the neurotrophic effects of HMB in mouse neuroblastoma Neuro2a cells. In Neuro2a cells, HMB promotes differentiation to neurites independent from any effects on proliferation. These effects are mediated by activation of both the PI3K/Akt and the extracellular-signal-regulated kinases (ERK1/2 signaling as demonstrated by the use of specific inhibitors of these two pathways. As myocyte-enhancer factor 2 (MEF2 family of transcription factors are involved in neuronal survival and plasticity, the transcriptional activity and protein levels of MEF2 were also evaluated. HMB promoted MEF2-dependent transcriptional activity mediated by the activation of Akt and ERK1/2 pathways. Furthermore, HMB increases the expression of brain glucose transporters 1 (GLUT1 and 3 (GLUT3, and mTOR phosphorylation, which translates in a higher protein synthesis in Neuro2a cells. Furthermore, Torin1 and rapamycin effects on MEF2 transcriptional activity and HMB-dependent neurite outgrowth support that HMB acts through mTORC2. Together, these findings provide clear evidence to support an important role of HMB in neurite outgrowth.

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

    Science.gov (United States)

    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.

  5. Recent advances in plaque, gingivitis, tartar and caries prevention technology.

    Science.gov (United States)

    Gaffar, A; Afflitto, J; Nabi, N; Herles, S; Kruger, I; Olsen, S

    1994-02-01

    A dentifrice containing triclosan/PVM/MA, copolymer/NaF (Total) combination was compared with dentifrices containing triclosan without the copolymer system. A variety of laboratory, animal and human studies indicated that Total provided higher uptake and retention of triclosan on teeth, and was more effective in reducing plaque in chemostat and flow cell models. The retention of triclosan in dental plaque was significantly higher with Total as compared with other dentifrices 2 hours post brushing. The triclosan retained in the plaque after using Total was effective against plaque bacteria for up to 12 hours. Other dentifrices did not provide a sustained antibacterial effect against plaque. The results indicated that the delivery system with the copolymer significantly enhanced the efficacy of triclosan against plaque, gingivitis and plaque related diseases in vivo.

  6. 18FDG PET and ultrasound echolucency in carotid artery plaques

    DEFF Research Database (Denmark)

    Graebe, Martin; Pedersen, Sune F; Højgaard, Liselotte

    2010-01-01

    OBJECTIVES: The objective was to evaluate inflammation in echolucent carotid artery plaques. BACKGROUND: Ultrasound echolucency of carotid artery plaques has been proven to differentiate patients at high risk of stroke. On the other hand, positron emission tomography (PET) of plaques with the use...... for ultrasound and PET imaging. Plaque standardized gray scale medians (GSM) were measured in longitudinal ultrasound images to quantitate echolucency, and GSM values were compared with FDG PET uptake quantified by maximum standardized uptake values (SUV). Symptomatic plaques were compared with contralateral...... plaques ranged from high to low inflammatory activity, as depicted with PET. Quantitative FDG SUV differentiated asymptomatic from symptomatic plaques, whereas GSM values did not. There was a positive correlation between CD68 expression and FDG uptake (r = 0.50, p = 0.04). CONCLUSIONS: Our results...

  7. Reliability and discriminatory power of methods for dental plaque quantification

    Directory of Open Access Journals (Sweden)

    Daniela Prócida Raggio

    2010-04-01

    Full Text Available OBJECTIVE: This in situ study evaluated the discriminatory power and reliability of methods of dental plaque quantification and the relationship between visual indices (VI and fluorescence camera (FC to detect plaque. MATERIAL AND METHODS: Six volunteers used palatal appliances with six bovine enamel blocks presenting different stages of plaque accumulation. The presence of plaque with and without disclosing was assessed using VI. Images were obtained with FC and digital camera in both conditions. The area covered by plaque was assessed. Examinations were done by two independent examiners. Data were analyzed by Kruskal-Wallis and Kappa tests to compare different conditions of samples and to assess the inter-examiner reproducibility. RESULTS: Some methods presented adequate reproducibility. The Turesky index and the assessment of area covered by disclosed plaque in the FC images presented the highest discriminatory powers. CONCLUSION: The Turesky index and images with FC with disclosing present good reliability and discriminatory power in quantifying dental plaque.

  8. New dimensions in mechanical plaque control: An overview

    Directory of Open Access Journals (Sweden)

    Arnab Mandal

    2017-01-01

    Full Text Available Plaque control is the daily removal of dental plaque, oral biofilm and also prevention of their accumulation on the teeth and other parts of oral cavity. Dental plaque is the major etiology of maximum gingival and periodontal diseases. It is also related with various dental problems. Mechanical plaque control is a very effective method to get rid of plaque accumulation in oral cavity. In 3000 BC there was the first toothbrush invented by human beings. With time several modifications came in toothbrushes to make mechanical plaque control more effective in day to day oral hygiene practice. This article emphasizes on the advanced and emerging tools in mechanical plaque control methods in attaining an optimal level of oral hygiene standards and maintenance of oral health.

  9. Three-dimensional carotid ultrasound plaque texture predicts vascular events

    DEFF Research Database (Denmark)

    van Engelen, Arna; Wannarong, Thapat; Parraga, Grace

    2014-01-01

    BACKGROUND AND PURPOSE: Carotid ultrasound atherosclerosis measurements, including those of the arterial wall and plaque, provide a way to monitor patients at risk of vascular events. Our objective was to examine carotid ultrasound plaque texture measurements and the change in carotid plaque...... texture during 1 year in patients at risk of events and to compare these with measurements of plaque volume and other risk factors as predictors of vascular events. METHODS: We evaluated 298 patients with carotid atherosclerosis using 3-dimensional (3D) ultrasound at baseline and after 1 year and measured...... carotid plaque volume and 376 measures of plaque texture. Patients were followed up to 5 years (median [range], 3.12 [0.77-4.66]) for myocardial infarction, transient ischemic attack, and stroke. Sparse Cox regression was used to select the most predictive plaque texture measurements in independent...

  10. Effect of Intensive Statin Therapy on Coronary High-Intensity Plaques Detected by Noncontrast T1-Weighted Imaging: The AQUAMARINE Pilot Study.

    Science.gov (United States)

    Noguchi, Teruo; Tanaka, Atsushi; Kawasaki, Tomohiro; Goto, Yoichi; Morita, Yoshiaki; Asaumi, Yasuhide; Nakao, Kazuhiro; Fujiwara, Reiko; Nishimura, Kunihiro; Miyamoto, Yoshihiro; Ishihara, Masaharu; Ogawa, Hisao; Koga, Nobuhiko; Narula, Jagat; Yasuda, Satoshi

    2015-07-21

    Coronary high-intensity plaques detected by noncontrast T1-weighted imaging may represent plaque instability. High-intensity plaques can be quantitatively assessed by a plaque-to-myocardium signal-intensity ratio (PMR). This pilot, hypothesis-generating study sought to investigate whether intensive statin therapy would lower PMR. Prospective serial noncontrast T1-weighted magnetic resonance imaging and computed tomography angiography were performed in 48 patients with coronary artery disease at baseline and after 12 months of intensive pitavastatin treatment with a target low-density lipoprotein cholesterol level parameters and high-sensitivity C-reactive protein levels were analyzed. In the statin group, 12 months of statin therapy significantly improved low-density lipoprotein cholesterol levels (125 to 70 mg/dl; p intensity plaques. Noncontrast T1-weighted magnetic resonance imaging could become a useful technique for repeated quantitative assessment of plaque composition. (Attempts at Plaque Vulnerability Quantification with Magnetic Resonance Imaging Using Noncontrast T1-weighted Technique [AQUAMARINE]; UMIN000003567). Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  11. Two new dendrocandins with neurite outgrowth-promoting activity from Dendrobium officinale.

    Science.gov (United States)

    Yang, Liu; Liu, Shou-Jin; Luo, Huai-Rong; Cui, Juan; Zhou, Jun; Wang, Xuan-Jun; Sheng, Jun; Hu, Jiang-Miao

    2015-01-01

    Two new bibenzyl derivatives, dendrocandin T (1) and dendrocandin U (2), together with eight known bibenzyls, were isolated from the stems of Dendrobium officinale. Those compounds were sent for the first time for central nervous system-related bioassay and the results indicated that compounds 3, 4, and 5 have a certain degree of neurite outgrowth-promoting activity, and compounds 1, 2, 6, and 7 also have weak activity. The results indicated that D. officinale used as health food and traditional Chinese medicine "Tiepi Shihu" has a health function of neurotrophic effects.

  12. Berberine, a natural antidiabetes drug, attenuates glucose neurotoxicity and promotes Nrf2-related neurite outgrowth

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, Ya-Yun [Department of Pharmacology, School of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Tseng, Yu-Ting [Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Lo, Yi-Ching, E-mail: yichlo@kmu.edu.tw [Department of Pharmacology, School of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China)

    2013-11-01

    Reactive oxygen intermediates production and apoptotic damage induced by high glucose are major causes of neuronal damage in diabetic neuropathy. Berberine (BBR), a natural antidiabetes drug with PI3K-activating activity, holds promise for diabetes because of its dual antioxidant and anti-apoptotic activities. We have previously reported that BBR attenuated H{sub 2}O{sub 2} neurotoxicity via activating the PI3K/Akt/Nrf2-dependent pathway. In this study, we further explored the novel protective mechanism of BBR on high glucose-induced apoptotic death and neurite damage of SH-SY5Y cells. Results indicated BBR (0.1–10 nM) significantly attenuated reactive oxygen species (ROS) production, nucleus condensation, and apoptotic death in high glucose-treated cells. However, AG1024, an inhibitor of insulin growth factor-1 (IGF-1) receptor, significantly abolished BBR protection against high glucose-induced neuronal death. BBR also increased Bcl-2 expression and decreased cytochrome c release. High glucose down-regulated IGF-1 receptor and phosphorylation of Akt and GSK-3β, the effects of which were attenuated by BBR treatment. BBR also activated nuclear erythroid 2-related factor 2 (Nrf2), the key antioxidative transcription factor, which is accompanied with up-regulation of hemeoxygenase-1 (HO-1). Furthermore, BBR markedly enhanced nerve growth factor (NGF) expression and promoted neurite outgrowth in high glucose-treated cells. To further determine the role of the Nrf2 in BBR neuroprotection, RNA interference directed against Nrf2 was used. Results indicated Nrf2 siRNA abolished BBR-induced HO-1, NGF, neurite outgrowth and ROS decrease. In conclusion, BBR attenuated high glucose-induced neurotoxicity, and we are the first to reveal this novel mechanism of BBR as an Nrf2 activator against glucose neurotoxicity, providing another potential therapeutic use of BBR on the treatment of diabetic complications. - Highlights: • BBR attenuates high glucose-induced ROS

  13. Inhibition of lysophosphatidic acid-induced neurite retraction and cell rounding by SR 57746A.

    Science.gov (United States)

    Magazin, M; Schiltz, P; Zachayus, J L; Cavrois, E; Caput, D; Ferrara, P

    1998-01-01

    Rapid neurite retraction and transient rounding of serum-starved NG108-15 and PC12 cells by lysophosphatidic acid (LPA) is retarded and reduced by pre-incubation of the cells with the small non-peptidic molecule, SR 57746A, which exhibits neurotrophic properties. The compound also antagonizes the redistribution of filamentous actin by LPA in both cell types. We hypothesize that the SR 57746A attenuation of LPA-induced effects may account for at least some of the neuroprotective properties of this molecule.

  14. Oculocutaneous albinism complicated with an ulcerated plaque

    Directory of Open Access Journals (Sweden)

    Lokanatha Keshavalu

    2013-04-01

    Full Text Available A 32-year-old male with a history of albinism and farmer by occupation presented with an ulcerated plaque on the right wrist. The patient had light eyes, hair, and skin. Physical examination showed extensive photodamage. A skin biopsy specimen from the plaque revealed a well-differentiated squamous-cell carcinoma. Wide surgical excision was done. The most common types of oculocutaneous albinism (OCA, OCA 1 and OCA 2, are autosomal recessive disorders of pigmentation that commonly affect the skin, hair and eyes. Photodamage and skin cancers plague patients with albinism. Albinos face a myriad of social and medical issues. Importance of photoprotection, skin cancer surveillance and treatment has been stressed upon in this report.

  15. Reducing allergic symptoms through eliminating subgingival plaque

    Directory of Open Access Journals (Sweden)

    Haryono Utomo

    2008-12-01

    Full Text Available Background: Elimination of subgingival plaque for prevention and treatment of periodontal diseases through scaling is a routine procedure. It is also well-known that periodontal disease is related to systemic diseases. Nevertheless, the idea how scaling procedures also able to reduce allergic symptoms i.e. eczema and asthma, is not easily accepted, because it is contradictory to the “hygiene hypothesis”. However, since allergic symptoms also depend on variable factors such as genetic, environmental and infection factors; every possible effort to eliminate or avoid from these factors had to be considered. Subgingival plaque is a source of infection, especially the Gram-negative bacteria that produced endotoxin (lipopolysaccharides, LPS, a potential stimulator of immunocompetent cells, which may also related to allergy, such as mast cells and basophils. In addition, it also triggers the “neurogenic switching” mechanism which may be initiated from chronic gingivitis. Objective: This case report may explain the possible connection between subgingival plaque and allergy based on evidence-based cases. Case: Two adult siblings who suffered from chronic gingivitis also showed different manifestations of allergy that were allergic dermatitis and asthma for years. They were also undergone unsuccessful medical treatment for years. Oral and topical corticosteroids were taken for dermatitis and inhalation for asthma. Case Management: Patients were conducted deep scaling procedures, allergic symptoms gradually diminished in days even though without usual medications. Conclusion: Concerning to the effectiveness of scaling procedures which concomitantly eliminate subgingival plaque in allergic patients, it concluded that this concept is logical. Nevertheless, further verification and collaborated study with allergic expert should be done.

  16. Vaporization of atherosclerotic plaques by spark erosion

    OpenAIRE

    Slager, Cornelis J.; Essed, Catharina E.; Schuurbiers, Johan C.H.; Bom, Nicolaas; Serruys, Patrick W.; Meester, Geert T.

    1985-01-01

    textabstractAn alternative to the laser irradiation of atherosclerotic lesions has been developed. A pulsed electrocardiogram R wave-triggered electrical spark erosion technique is described. Controlled vaporization of fibrous and lipid plaques with minimal thermal side effects was achieved and documented histologically in vitro from 30 atherosclerotic segments of six human aortic autopsy specimens. Craters with a constant area and a depth that varied according to the duration of application ...

  17. Reducing allergic symptoms through eliminating subgingival plaque

    OpenAIRE

    Utomo, Haryono; Prahasanti, Chiquita; Ruhadi, Iwan

    2008-01-01

    Background: Elimination of subgingival plaque for prevention and treatment of periodontal diseases through scaling is a routine procedure. It is also well-known that periodontal disease is related to systemic diseases. Nevertheless, the idea how scaling procedures also able to reduce allergic symptoms i.e. eczema and asthma, is not easily accepted, because it is contradictory to the “hygiene hypothesis”. However, since allergic symptoms also depend on variable factors such as genetic, environ...

  18. Trans-corporal incision of Peyronie's plaques.

    Science.gov (United States)

    Shaeer, Osama

    2011-02-01

    Patients presenting with Peyronie's disease (PD) curvature and erectile dysfunction (ED) can achieve straightening and rigidity through penile prosthesis implantation and manual modeling and, if necessary, a relaxing tunical incision with or without grafting. Unfortunately, this maneuver will not correct PD-induced shortening. In addition, incision and grafting after the prosthesis has already been implanted adds to operative time and risk, and may indicate mobilization of the neurovascular bundle and, possibly, a secondary skin incision. This work describes trans-corporal incision (TCI), a minimally invasive endoscopic approach for plaque incision from within the corpora cavernosa, restoring straightness and length to the penis, before calibration of the corpora cavernosa, allowing implantation of a longer prosthesis in a straight penis, with neither mobilizing the neurovascular bundle nor a secondary incision. Sixteen patients with PD deformity and refractory ED were operated upon. Intra-operative artificial erection demonstrated the deformity. Through a penoscrotal incision, the corpora were dilated. TCI was performed to incise Peyronie's plaques at the point of maximum deformity. Artificial erection was re-induced and correction of curvature evaluated. Length was measured before and after TCI. Implantation proceeded as usual. Penile straightness and length. Following implantation, the penis was straight in all cases. Pre-TCI length of the corpora was unequal on either side. Post-TCI, both corpora were of equal length with an average increase of 2.5 cm (11.9%) on the right side and 1.9 (9.1%) on the left. TCI; corporoscopic incision of Peyronie's plaques upon implantation of penile prosthesis is a minimally invasive approach that restores both straightness and length to patients with PD and ED, with neither mobilization of the neurovascular bundle nor plaque incision and grafting. © 2010 International Society for Sexual Medicine.

  19. Relationship between dyslipidemia and carotid plaques in a high-stroke-risk population in Shandong Province, China.

    Science.gov (United States)

    Mi, Te; Sun, Shangwen; Zhang, Guoqing; Carora, Yaser; Du, Yifeng; Guo, Shougang; Cao, Mingfeng; Zhu, Qiang; Wang, Yongxiang; Sun, Qinjian; Wang, Xiang; Qu, Chuanqiang

    2016-06-01

    The precise associations between stroke and carotid plaques and dyslipidemia are unclear. This population-based study aimed to examine the relationship between carotid plaques and dyslipidemia in a high-stroke-risk population. Ultrasonography of left and right carotid arteries was conducted in 22,222 participants in a second screening survey of individuals with high stroke risk. Subjects were divided into two groups according to the presence or absence of carotid plaques. Blood TC (total cholesterol), TG (total triglycerides), and LDL-C (low-density lipoprotein cholesterol) levels were recorded. Multivariate logistic regression analysis, controlled for gender, age, education, geographic region, smoking, exercise, and overweight (Model 2), identified TG as a predictor of carotid-plaque risk (odds ratio [OR] = 1.109, 95% confidence interval [CI]: 1.038-1.185, P = 0.002), and the association between carotid plaques and LDL-C (OR = 0.967, 95%CI: 0.949-0.994, P = 0.019) was less significant, whereas there was no association between carotid plaques and TC (OR = 1.002, 95%CI: 0.932-1.007, P = 0.958). After additional adjustment for hypertension, diabetes, and atrial fibrillation (Model 3), TG remained a risk factor for carotid plaques (OR = 1.086, 95%CI: 1.016-1.161, P = 0.015), but no associations were observed between carotid plaques and LDL-C (OR = 0.972, 95%CI: 0.910-1.038, P = 0.394) or TC (OR = 1.003, 95%CI: 0.933-1.079, P = 0.928). Only the association between TG and carotid plaques (OR = 1.084, 95%CI: 1.014-1.159, P = 0.017) was independent of all covariates (covariates in Model 3 plus history of stroke or transient ischemic attack, and stroke family history) in Model 4. These findings indicate that TG was an independent risk factor for carotid plaques in high-risk population for stroke, whereas LDL-C and TC were not associated with the appearance of carotid plaques independently.

  20. Helicobacter pylori in dental plaque; is it related to brushing frequency, plaque load and oral health status?

    Science.gov (United States)

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

    2011-10-01

    To determine the relation between presence of H. pylori in supra-gingival dental plaque with oral hygiene habits and oral health status of patients suffering from symptomatic dyspepsia. Descriptive study. The Department of Oral Health Sciences, Shaikh Zayed FPGMI, Lahore, from September 2008 to August 2009. One hundred and fifty dyspeptic subjects with dental plaque were enrolled. After recording brushing frequency, oral health status and plaque load, the supra-gingival dental plaque samples were collected by sterile curettes. Helicobacter pylori were detected in dental plaque samples through PCR assay. Presence of H. pylori in dental plaque was found to be 37.5% in the sample. Most of the subjects brushed once daily, had plaque index score of 1 and had fair to poor oral hygiene status. Approximately 35% of the individuals who brushed once or twice a day harbored the bacterium in their dental plaque. There was no difference between bacterial detection rates among different categories of plaque index and oral health status of the study subjects. Presence of H. pylori in dental plaque was found to be associated with neither brushing frequency nor with the plaque load nor with the oral health status of individuals suffering from symptomatic dyspepsia.

  1. Stimulation of myenteric plexus neurite outgrowth by insulin and insulin-like growth factors I and II.

    Science.gov (United States)

    Mulholland, M W; Romanchuk, G; Simeone, D M; Flowe, K

    1992-01-01

    A defined culture medium containing insulin, insulin-like growth factor I (IGF-I) or insulin-like growth factor II (IGF-II) supported morphological development of myenteric plexus neurons derived from neonatal guinea pigs. Insulin increased neurite outgrowth 3-fold at concentrations as low as 0.2 nM. Similar significant and dose-dependent increases in neurite outgrowth were noted with IGF-I and IGF-II. Stimulation of neurite outgrowth was abolished by exposure to cytosine arabinofuranoside, an agent toxic to non-neuronal cells, implying that trophic effects of insulin or insulin-like growth factors require the presence of non-neuronal elements in culture.

  2. Ghrelin inhibits atherosclerotic plaque angiogenesis and promotes plaque stability in a rabbit atherosclerotic model.

    Science.gov (United States)

    Wang, Li; Chen, Qingwei; Ke, Dazhi; Li, Guiqiong

    2017-04-01

    Intraplaque angiogenesis associates with the instability of atherosclerotic plaques. In the present study, we investigated the effects of ghrelin on intraplaque angiogenesis and plaque instability in a rabbit model of atherosclerosis. The rabbits were randomly divided into three groups, namely, the control group, atherosclerotic model group, and ghrelin-treated group, with treatments lasting for 4 weeks. We found that the thickness ratio of the intima to media in rabbits of the ghrelin-treated group was significantly lower than that in rabbits of the atherosclerotic model group. The number of neovessels and the levels of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (VEGFR2) decreased dramatically in rabbits of the ghrelin-treated group compared to those of the atherosclerotic model group. Ghrelin significantly decreased the plaque content of macrophages, matrix metalloproteinase (MMP)-2, and MMP-9, in a rabbit model of atherosclerosis. In addition, the level of the pro-inflammatory factor monocyte chemoattractant protein (MCP)-1 was significantly lower in rabbits of the ghrelin-treated group than in rabbits of the atherosclerotic model group. In summary, ghrelin can inhibit intraplaque angiogenesis and promote plaque stability by down-regulating VEGF and VEGFR2 expression, inhibiting the plaque content of macrophages, and reducing MCP-1 expression at an advanced stage of atherosclerosis in rabbits. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Assessment of plaque regrowth with a probiotic toothpaste containing Lactobacillus paracasei: A spectrophotometric study

    Directory of Open Access Journals (Sweden)

    Shruti Srinivasan

    2017-01-01

    Full Text Available Background: Probiotics are live microorganisms which when administered in adequate amounts confer health benefits on the host. Commonly, most of the organisms ascribed as having probiotic properties belong to the genera Lactobacillus and Bifidobacterium and milk is the most commonly used vehicle. Objectives: The study was aimed at analyzing the biofilm formation by plaque regrowth method upon the usage of a probiotic toothpaste containing Lactobacillus paracasei by measuring the optical density using a spectrophotometer.Materials and Methods: A commercially available probiotic toothpaste, PerioBiotic (spearmint flavored from the company Designs for Health, has been tested. The toothpaste contains the strain L. paracasei, which has been found to co-aggregate with Streptococcus mutans (MS. The Plaque Glycolysis and Regrowth Method (PGRM was used for the evaluation of the antimicrobial effects on plaque metabolism in vivo. PGRM is based on the observation that natural fasted dental plaque, sampled from different quadrants of the dentition, exhibits similar metabolic and regrowth properties when suspended at equal “biomass” in standardized media. Conclusion: The results suggest that L. paracasei-based toothpaste, PerioBiotic, is effective in the reduction of MSmonospecies biofilm, but the activity appears short lived when high sucrose exposure is administered.

  4. Numerical simulation of blood flow and plaque progression in carotid-carotid bypass patient specific case.

    Science.gov (United States)

    Filipovic, Nenad; Saveljic, Igor; Nikolic, Dalibor; Milosevic, Zarko; Kovacevic, Pavle; Velicki, Lazar

    2015-01-01

    This study describes computer simulation of blood flow and plaque progression pattern in a patient who underwent surgical treatment for infected carotid prosthetic tube graft using carotid-carotid cross-over bypass. The 3D blood flow is governed by the Navier-Stokes equations, together with the continuity equation. Mass transfer within the blood lumen and through the arterial wall is coupled with the blood flow and is modelled by the convection-diffusion equation. Low-density lipoprotein (LDL) transport in lumen of the vessel is described by Kedem-Katchalsky equations. The inflammatory process is solved using three additional reaction-diffusion partial differential equations. Calculation based on a computer simulation showed that flow distribution in the left carotid artery (CA) was around 40-50% of the total flow in the right common CA. Also, the left CA had higher pressure gradient after surgical intervention. Plaque progression simulation predicted development of the atherosclerotic plaque in the position of the right common CA and the left internal CA. A novel way of atherosclerotic plaque progression modelling using computer simulation shows a potential clinical benefit with significant impact on the treatment strategy optimization.

  5. Phosphatidylinositol 4-phosphate 5-kinase α negatively regulates nerve growth factor-induced neurite outgrowth in PC12 cells.

    Science.gov (United States)

    Liu, Tian; Lee, Sang Yoon

    2013-03-29

    Neurite outgrowth, a cell differentiation process involving membrane morphological changes, is critical for neuronal network and development. The membrane lipid, phosphatidylinositol (PI) 4,5-bisphosphate (PIP2), is a key regulator of many important cell surface events of membrane signaling, trafficking and dynamics. This lipid is produced mainly by the type I PI 4-phosphate 5-kinase (PIP5K) family members. In this study, we addressed whether PIP5Kα, an isoform of PIP5K, could have a role in neurite outgrowth induced by nerve growth factor (NGF). For this purpose, we knocked down PIP5Kα in PC12 rat pheochromocytoma cells by stable expression of PIP5Kα microRNA that significantly reduced PIP5Kα expression and PIP2 level. Interestingly, NGF-induced neurite outgrowth was more prominent in PIP5Kα-knockdown (KD) cells than in control cells. Conversely, add-back of PIP5Kα into PIP5Kα KD cells abrogated the effect of NGF on neurite outgrowth. NGF treatment activated PI 3-kinase (PI3K)/Akt pathway, which seemed to be associated with reactive oxygen species generation. Similar to the changes in neurite outgrowth, the PI3K/Akt activation by NGF was potentiated by PIP5Kα KD, but was attenuated by the reintroduction of PIP5Kα. Moreover, exogenously applied PIP2 to PIP5Kα KD cells also suppressed Akt activation by NGF. Together, our results suggest that PIP5Kα acts as a negative regulator of NGF-induced neurite outgrowth by inhibiting PI3K/Akt signaling pathway in PC12 cells.

  6. Effect of different densities of silver nanoparticles on neuronal growth

    Energy Technology Data Exchange (ETDEWEB)

    Nissan, Ifat [Bar-Ilan University, Department of Chemistry (Israel); Schori, Hadas [Bar-Ilan University, Faculty of Engineering (Israel); Lipovsky, Anat [Bar-Ilan University, Department of Chemistry (Israel); Alon, Noa [Bar-Ilan University, Faculty of Engineering (Israel); Gedanken, Aharon, E-mail: gedanken@biu.ac.il [Bar-Ilan University, Department of Chemistry (Israel); Shefi, Orit, E-mail: orit.shefi@biu.ac.il [Bar-Ilan University, Faculty of Engineering (Israel)

    2016-08-15

    Nerve regeneration has become a subject of great interest, and much effort is devoted to the design and manufacturing of effective biomaterials. In this paper, we report the capability of surfaces coated with silver nanoparticles (AgNPs) to serve as platforms for nerve regeneration. We fabricated substrates coated with silver nanoparticles at different densities using sonochemistry, and grew neuroblastoma cells on the AgNPs. The effect of the different densities on the development of the neurites during the initiation and elongation growth phases was studied. We found that the AgNPs function as favorable anchoring sites for the neuroblastoma cells, significantly enhancing neurite outgrowth. One of the main goals of this study is to test whether the enhanced growth of the neurites is due to the mere presence of AgNPs or whether their topography also plays a vital role. We found that this phenomenon was repeated for all the tested densities, with a maximal effect for the substrates that are coated with 45 NPs/μm{sup 2}. We also studied the amount of reactive oxygen spices (ROS) in the presence of AgNPs as indicator of cell activation. Our results, combined with the well-known antibacterial effects of AgNPs, suggest that substrates coated with AgNP are attractive nanomaterials—with dual activity—for neuronal repair studies and therapeutics.Graphical Abstract.

  7. Potentiation of nerve growth factor-induced neurite outgrowth in PC12 cells by ifenprodil: the role of sigma-1 and IP3 receptors.

    Directory of Open Access Journals (Sweden)

    Tamaki Ishima

    Full Text Available In addition to both the α1 adrenergic receptor and N-methyl-D-aspartate (NMDA receptor antagonists, ifenprodil binds to the sigma receptor subtypes 1 and 2. In this study, we examined the effects of ifenprodil on nerve growth factor (NGF-induced neurite outgrowth in PC12 cells. Ifenprodil significantly potentiated NGF-induced neurite outgrowth, in a concentration-dependent manner. In contrast, the α1 adrenergic receptor antagonist, prazosin and the NMDA receptor NR2B antagonist, Ro 25-6981 did not alter NGF-induced neurite outgrowth. Potentiation of NGF-induced neurite outgrowth mediated by ifenprodil was significantly antagonized by co-administration of the selective sigma-1 receptor antagonist, NE-100, but not the sigma-2 receptor antagonist, SM-21. Similarly, ifenprodil enhanced NGF-induced neurite outgrowth was again significantly reduced by the inositol 1,4,5-triphosphate (IP(3 receptor antagonists, xestospongin C and 2-aminoethoxydiphenyl borate (2-APB treatment. Furthermore, BAPTA-AM, a chelator of intracellular Ca(2+, blocked the effects of ifenprodil on NGF-induced neurite outgrowth, indicating the role of intracellular Ca(2+ in the neurite outgrowth. These findings suggest that activation at sigma-1 receptors and subsequent interaction with IP(3 receptors may mediate the pharmacological effects of ifenprodil on neurite outgrowth.

  8. Orexin A Inhibits Propofol-Induced Neurite Retraction by a Phospholipase D/Protein Kinase Cε-Dependent Mechanism in Neurons

    Science.gov (United States)

    Björnström, Karin; Turina, Dean; Strid, Tobias; Sundqvist, Tommy; Eintrei, Christina

    2014-01-01

    Background The intravenous anaesthetic propofol retracts neurites and reverses the transport of vesicles in rat cortical neurons. Orexin A (OA) is an endogenous neuropeptide regulating wakefulness and may counterbalance anaesthesia. We aim to investigate if OA interacts with anaesthetics by inhibition of the propofol-induced neurite retraction. Methods In primary cortical cell cultures from newborn rats’ brains, live cell light microscopy was used to measure neurite retraction after propofol (2 µM) treatment with or without OA (10 nM) application. The intracellular signalling involved was tested using a protein kinase C (PKC) activator [phorbol 12-myristate 13-acetate (PMA)] and inhibitors of Rho-kinase (HA-1077), phospholipase D (PLD) [5-fluoro-2-indolyl des-chlorohalopemide (FIPI)], PKC (staurosporine), and a PKCε translocation inhibitor peptide. Changes in PKCε Ser729 phosphorylation were detected with Western blot. Results The neurite retraction induced by propofol is blocked by Rho-kinase and PMA. OA blocks neurite retraction induced by propofol, and this inhibitory effect could be prevented by FIPI, staurosporine and PKCε translocation inhibitor peptide. OA increases via PLD and propofol decreases PKCε Ser729 phosphorylation, a crucial step in the activation of PKCε. Conclusions Rho-kinase is essential for propofol-induced neurite retraction in cortical neuronal cells. Activation of PKC inhibits neurite retraction caused by propofol. OA blocks propofol-induced neurite retraction by a PLD/PKCε-mediated pathway, and PKCε maybe the key enzyme where the wakefulness and anaesthesia signal pathways converge. PMID:24828410

  9. Oligomerization of ZFYVE27 (Protrudin is necessary to promote neurite extension.

    Directory of Open Access Journals (Sweden)

    D V Krishna Pantakani

    Full Text Available ZFYVE27 (Protrudin was originally identified as an interacting partner of spastin, which is most frequently mutated in hereditary spastic paraplegia. ZFYVE27 is a novel member of FYVE family, which is implicated in the formation of neurite extensions by promoting directional membrane trafficking in neurons. Now, through a yeast two-hybrid screen, we have identified that ZFYVE27 interacts with itself and the core interaction region resides within the third hydrophobic region (HR3 of the protein. We confirmed the ZFYVE27's self-interaction in the mammalian cells by co-immunoprecipitation and co-localization studies. To decipher the oligomeric nature of ZFYVE27, we performed sucrose gradient centrifugation and showed that ZFYVE27 oligomerizes into dimer/tetramer forms. Sub-cellular fractionation and Triton X-114 membrane phase separation analysis indicated that ZFYVE27 is a peripheral membrane protein. Furthermore, ZFYVE27 also binds to phosphatidylinositol 3-phosphate lipid moiety. Interestingly, cells expressing ZFYVE27(ΔHR3 failed to produce protrusions instead caused swelling of cell soma. When ZFYVE27(ΔHR3 was co-expressed with wild-type ZFYVE27 (ZFYVE27(WT, it exerted a dominant negative effect on ZFYVE27(WT as the cells co-expressing both proteins were also unable to induce protrusions and showed cytoplasmic swelling. Altogether, it is evident that a functionally active form of oligomer is crucial for ZFYVE27 ability to promote neurite extensions.

  10. Enhanced Neural Cell Adhesion and Neurite Outgrowth on Graphene-Based Biomimetic Substrates

    Science.gov (United States)

    Lee, Jong Ho; Kang, Seok Hee; Hwang, Eun Young; Hwang, Yu-Shik; Lee, Mi Hee; Park, Jong-Chul

    2014-01-01

    Neural cell adhesion and neurite outgrowth were examined on graphene-based biomimetic substrates. The biocompatibility of carbon nanomaterials such as graphene and carbon nanotubes (CNTs), that is, single-walled and multiwalled CNTs, against pheochromocytoma-derived PC-12 neural cells was also evaluated by quantifying metabolic activity (with WST-8 assay), intracellular oxidative stress (with ROS assay), and membrane integrity (with LDH assay). Graphene films were grown by using chemical vapor deposition and were then coated onto glass coverslips by using the scooping method. Graphene sheets were patterned on SiO2/Si substrates by using photolithography and were then covered with serum for a neural cell culture. Both types of CNTs induced significant dose-dependent decreases in the viability of PC-12 cells, whereas graphene exerted adverse effects on the neural cells just at over 62.5 ppm. This result implies that graphene and CNTs, even though they were the same carbon-based nanomaterials, show differential influences on neural cells. Furthermore, graphene-coated or graphene-patterned substrates were shown to substantially enhance the adhesion and neurite outgrowth of PC-12 cells. These results suggest that graphene-based substrates as biomimetic cues have good biocompatibility as well as a unique surface property that can enhance the neural cells, which would open up enormous opportunities in neural regeneration and nanomedicine. PMID:24592382

  11. Neuroprotective and neuroregenerative effects of nimodipine in a model system of neuronal differentiation and neurite outgrowth.

    Science.gov (United States)

    Bork, Kaya; Wurm, Franziska; Haller, Hannes; Strauss, Christian; Scheller, Christian; Gnanapragassam, Vinayaga S; Horstkorte, Rüdiger

    2015-01-09

    Nimodipine is a Ca2+-channel antagonist mainly used for the management of aneurysmal subarachnoid hemorrhage (aSAH) to prevent cerebral vasospasms. However, it is not clear if the better outcome of nimodipine-treated patients is mainly due to vasodilatation or whether other cellular neuroprotective or neuregenerative effects of nimodipine are involved. We analysed PC12 cells after different stress stimuli with or without nimodipine pretreatment. Cytotoxicity of 200 mM EtOH and osmotic stress (450 mosmol/L) was significantly reduced with nimodipine pretreatment, while nimodipine has no influence on the hypoxia-induced cytotoxicity in PC12 cells. The presence of nimodipine also increased the NGF-induced neurite outgrowth in PC12 cells. However, nimodipine alone was not able to induce neurite outgrowth in PC12 cells. These results support the idea that nimodipine has general neuroprotective or neuregenerative effect beside its role in vasodilatation and is maybe useful also in other clinical applications beside aSAH.

  12. Neuroprotective and Neuroregenerative Effects of Nimodipine in a Model System of Neuronal Differentiation and Neurite Outgrowth

    Directory of Open Access Journals (Sweden)

    Kaya Bork

    2015-01-01

    Full Text Available Nimodipine is a Ca2+-channel antagonist mainly used for the management of aneurysmal subarachnoid hemorrhage (aSAH to prevent cerebral vasospasms. However, it is not clear if the better outcome of nimodipine-treated patients is mainly due to vasodilatation or whether other cellular neuroprotective or neuregenerative effects of nimodipine are involved. We analysed PC12 cells after different stress stimuli with or without nimodipine pretreatment. Cytotoxicity of 200 mM EtOH and osmotic stress (450 mosmol/L was significantly reduced with nimodipine pretreatment, while nimodipine has no influence on the hypoxia-induced cytotoxicity in PC12 cells. The presence of nimodipine also increased the NGF-induced neurite outgrowth in PC12 cells. However, nimodipine alone was not able to induce neurite outgrowth in PC12 cells. These results support the idea that nimodipine has general neuroprotective or neuregenerative effect beside its role in vasodilatation and is maybe useful also in other clinical applications beside aSAH.

  13. Study of laser uncaging induced morphological alteration of rat cortical neurites using atomic force microscopy.

    Science.gov (United States)

    Tian, Jian; Tu, Chunlong; Liang, Yitao; Zhou, Jian; Ye, Xuesong

    2015-09-30

    Activity-dependent structural remodeling is an important aspect of neuronal plasticity. In the previous researches, neuronal structure variations resulting from external interventions were detected by the imaging instruments such as the fluorescence microscopy, the scanning/transmission electron microscopy (SEM/TEM) and the laser confocal microscopy. In this article, a new platform which combined the photochemical stimulation with atomic force microscopy (AFM) was set up to detect the activity-dependent structural remodeling. In the experiments, the cortical neurites on the glass coverslips were stimulated by locally uncaged glutamate under the ultraviolet (UV) laser pulses, and a calcium-related structural collapse of neurites (about 250 nm height decrease) was observed by an AFM. This was the first attempt to combine the laser uncaging with AFM in living cell researches. With the advantages of highly localized stimulation (<5 μm), super resolution imaging (<3.8 nm), and convenient platform building, this system was suitable for the quantitative observation of the neuron mechanical property variations and morphological alterations modified by neural activities under different photochemical stimulations, which would be helpful for studying physiological and pathological mechanisms of structural and functional changes induced by the biomolecule acting. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Enhancement of neurite outgrowth in neuron cancer stem cells by growth on 3-D collagen scaffolds

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    Chen, Chih-Hao [Department of Electrical Engineering, I-Shou University, Taiwan, ROC (China); Neurosurgery, Department of Surgery, Kaohsiung Veterans General Hospital, Taiwan, ROC (China); Department of Biomedical Engineering, I-Shou University, Taiwan, ROC (China); Kuo, Shyh Ming [Department of Biomedical Engineering, I-Shou University, Taiwan, ROC (China); Liu, Guei-Sheung [Centre for Eye Research Australia, University of Melbourne (Australia); Chen, Wan-Nan U. [Department of Biological Science and Technology, I-Shou University, Taiwan, ROC (China); Chuang, Chin-Wen [Department of Electrical Engineering, I-Shou University, Taiwan, ROC (China); Liu, Li-Feng, E-mail: liulf@isu.edu.tw [Department of Biological Science and Technology, I-Shou University, Taiwan, ROC (China)

    2012-11-09

    Highlights: Black-Right-Pointing-Pointer Neuron cancer stem cells (NCSCs) behave high multiply of growth on collagen scaffold. Black-Right-Pointing-Pointer Enhancement of NCSCs neurite outgrowth on porous collagen scaffold. Black-Right-Pointing-Pointer 3-D collagen culture of NCSCs shows an advance differentiation than 2-D culture. -- Abstract: Collagen is one component of the extracellular matrix that has been widely used for constructive remodeling to facilitate cell growth and differentiation. The 3-D distribution and growth of cells within the porous scaffold suggest a clinical significance for nerve tissue engineering. In the current study, we investigated proliferation and differentiation of neuron cancer stem cells (NCSCs) on a 3-D porous collagen scaffold that mimics the natural extracellular matrix. We first generated green fluorescence protein (GFP) expressing NCSCs using a lentiviral system to instantly monitor the transitions of morphological changes during growth on the 3-D scaffold. We found that proliferation of GFP-NCSCs increased, and a single cell mass rapidly grew with unrestricted expansion between days 3 and 9 in culture. Moreover, immunostaining with neuronal nuclei (NeuN) revealed that NCSCs grown on the 3-D collagen scaffold significantly enhanced neurite outgrowth. Our findings confirmed that the 80 {mu}m porous collagen scaffold could enhance attachment, viability and differentiation of the cancer neural stem cells. This result could provide a new application for nerve tissue engineering and nerve regeneration.

  15. Atlastin regulates store-operated calcium entry for nerve growth factor-induced neurite outgrowth.

    Science.gov (United States)

    Li, Jing; Yan, Bing; Si, Hongjiang; Peng, Xu; Zhang, Shenyuan L; Hu, Junjie

    2017-02-27

    Homotypic membrane fusion of the endoplasmic reticulum (ER) is mediated by a class of dynamin-like GTPases known as atlastin (ATL). Depletion of or mutations in ATL cause an unbranched ER morphology and hereditary spastic paraplegia (HSP), a neurodegenerative disease characterized by axon shortening in corticospinal motor neurons and progressive spasticity of the lower limbs. How ER shaping is linked to neuronal defects is poorly understood. Here, we show that dominant-negative mutants of ATL1 in PC-12 cells inhibit nerve growth factor (NGF)-induced neurite outgrowth. Overexpression of wild-type or mutant ATL1 or depletion of ATLs alters ER morphology and affects store-operated calcium entry (SOCE) by decreasing STIM1 puncta formation near the plasma membrane upon calcium depletion of the ER. In addition, blockage of the STIM1-Orai pathway effectively abolishes neurite outgrowth of PC-12 cells stimulated by NGF. These results suggest that SOCE plays an important role in neuronal regeneration, and mutations in ATL1 may cause HSP, partly by undermining SOCE.

  16. Nerve growth factor-immobilized polypyrrole: Bioactive electrically conducting polymer for enhanced neurite extension

    Science.gov (United States)

    Gomez, Natalia; Schmidt, Christine E.

    2010-01-01

    Biomaterials that present multiple stimuli are attractive for a number of biomedical applications. In particular, electrical and biological cues are important factors to include in interfaces with neurons for applications such as nerve conduits and neural probes. Here, we report the combination of these two stimuli, by immobilizing nerve growth factor (NGF) on the surface of the electrically conducting polymer polypyrrole (PPy). NGF was immobilized using an intermediate linker provided by a layer of polyallylamine conjugated to an arylazido functional group. Upon exposure to UV light and activation of the azido groups, NGF was fixed to the substrate. Three different surface concentrations were obtained (0.21–0.98 ng/mm2) and similar levels of neurite extension were observed on immobilized NGF as with soluble NGF. Additionally, electrical stimulation experiments were conducted with the modified polymer and revealed a 50% increase in neurite outgrowth in PC12 cells compared to experiments without electrical stimulation. This novel modification of PPy provides both electrical and biological stimulation, by presenting tethered growth factors and only producing a small decrease in the material's properties (conductivity ~10 S cm−1) when compared to other modification techniques (conductivity ~10−3–10−6 S cm−1. PMID:17111407

  17. RA-RAR-β counteracts myelin-dependent inhibition of neurite outgrowth via Lingo-1 repression.

    Science.gov (United States)

    Puttagunta, Radhika; Schmandke, André; Floriddia, Elisa; Gaub, Perrine; Fomin, Natalie; Ghyselinck, Norbert B; Di Giovanni, Simone

    2011-06-27

    After an acute central nervous system injury, axonal regeneration is limited as the result of a lack of neuronal intrinsic competence and the presence of extrinsic inhibitory signals. The injury fragments the myelin neuronal insulating layer, releasing extrinsic inhibitory molecules to signal through the neuronal membrane-bound Nogo receptor (NgR) complex. In this paper, we show that a neuronal transcriptional pathway can interfere with extrinsic inhibitory myelin-dependent signaling, thereby promoting neurite outgrowth. Specifically, retinoic acid (RA), acting through the RA receptor β (RAR-β), inhibited myelin-activated NgR signaling through the transcriptional repression of the NgR complex member Lingo-1. We show that suppression of Lingo-1 was required for RA-RAR-β to counteract extrinsic inhibition of neurite outgrowth. Furthermore, we confirm in vivo that RA treatment after a dorsal column overhemisection injury inhibited Lingo-1 expression, specifically through RAR-β. Our findings identify a novel link between RA-RAR-β-dependent proaxonal outgrowth and inhibitory NgR complex-dependent signaling, potentially allowing for the development of molecular strategies to enhance axonal regeneration after a central nervous system injury.

  18. RA–RAR-β counteracts myelin-dependent inhibition of neurite outgrowth via Lingo-1 repression

    Science.gov (United States)

    Puttagunta, Radhika; Schmandke, André; Floriddia, Elisa; Gaub, Perrine; Fomin, Natalie; Ghyselinck, Norbert B.

    2011-01-01

    After an acute central nervous system injury, axonal regeneration is limited as the result of a lack of neuronal intrinsic competence and the presence of extrinsic inhibitory signals. The injury fragments the myelin neuronal insulating layer, releasing extrinsic inhibitory molecules to signal through the neuronal membrane–bound Nogo receptor (NgR) complex. In this paper, we show that a neuronal transcriptional pathway can interfere with extrinsic inhibitory myelin-dependent signaling, thereby promoting neurite outgrowth. Specifically, retinoic acid (RA), acting through the RA receptor β (RAR-β), inhibited myelin-activated NgR signaling through the transcriptional repression of the NgR complex member Lingo-1. We show that suppression of Lingo-1 was required for RA–RAR-β to counteract extrinsic inhibition of neurite outgrowth. Furthermore, we confirm in vivo that RA treatment after a dorsal column overhemisection injury inhibited Lingo-1 expression, specifically through RAR-β. Our findings identify a novel link between RA–RAR-β–dependent proaxonal outgrowth and inhibitory NgR complex–dependent signaling, potentially allowing for the development of molecular strategies to enhance axonal regeneration after a central nervous system injury. PMID:21690307

  19. Improved Estimation of Coronary Plaque and Luminal Attenuation Using a Vendor-specific Model-based Iterative Reconstruction Algorithm in Contrast-enhanced CT Coronary Angiography.

    Science.gov (United States)

    Funama, Yoshinori; Utsunomiya, Daisuke; Hirata, Kenichiro; Taguchi, Katsuyuki; Nakaura, Takeshi; Oda, Seitaro; Kidoh, Masafumi; Yuki, Hideaki; Yamashita, Yasuyuki

    2017-09-01

    To investigate the stabilities of plaque attenuation and coronary lumen for different plaque types, stenotic degrees, lumen densities, and reconstruction methods using coronary vessel phantoms and the visualization of coronary plaques in clinical patients through coronary computed tomography (CT) angiography. We performed 320-detector volume scanning of vessel tubes with stenosis and a tube without stenosis using three types of plaque CT numbers. The stenotic degrees were 50% and 75%. Images were reconstructed with filtered back projection (FBP) and two types of iterative reconstructions (AIDR3D and FIRST [forward-projected model-based iterative reconstruction solution]), with stenotic CT number of approximately 40, 80, and 150 HU (Hounsfield unit), respectively. In each case, the tubing of the coronary vessel was filled with diluted contrast material and distilled water to reach the target lumen CT numbers of approximately 350 HU and 450 HU, and 0 HU, respectively. Peak lumen and plaque CT numbers were measured to calculate the lumen-plaque contrast. In addition, we retrospectively evaluated the image quality with regard to coronary arterial lumen and the plaque in 10 clinical patients on a 4-point scale. At 50% stenosis, the plaque CT number with contrast enhancement increased for FBP and AIDR3D, and the difference in the plaque CT number with and without contrast enhancement was 15-44 HU for FBP and 10-31 HU for AIDR3D. However, the plaque CT number for FIRST had a smaller variation and the difference with and without contrast enhancement was -12 to 8 HU. The visual evaluation score for the vessel lumen was 2.8 ± 0.6, 3.5 ± 0.5, and 3.7 ± 0.5 for FBP, AIDR3D, and FIRST, respectively. The FIRST method controls the increase in plaque density and the lumen-plaque contrast. Consequently, it improves the visualization of coronary plaques in coronary CT angiography. Copyright © 2017 The Association of University Radiologists. Published by

  20. Association between body mass index and presence of carotid plaque among low-income adults aged 45 years and older: a population-based cross-sectional study in rural China.

    Science.gov (United States)

    Lou, Yongzhong; Li, Bin; Su, Lan; Mu, Zhenhong; Sun, Minghao; Gu, Hongfei; Ni, Jingxian; Wu, Yanan; Tu, Jun; Wang, Jinghua; Ning, Xianjia

    2017-10-06

    Carotid plaque is a good surrogate endpoint for assessing arterial atherosclerosis, and atherosclerosis is a reliable predictor of cardiovascular diseases. However, the effect of body mass index on carotid plaque is unknown. Therefore, we aimed to explore the association between body mass index and carotid plaque in a low-income Chinese population. Residents aged ≥45 years and free of stroke and cardiovascular diseases were enrolled and divided into four groups based on body mass index. B-mode ultrasonography was performed to measure carotid plaque. The mean age of participants was 59.92 years overall. Significant correlations were observed between the presence of carotid plaque and male sex, older age, systolic blood pressure, fasting plasma glucose, and low-density lipoprotein cholesterol among the different BMI subgroups. Male sex increased the risk of carotid plaque in the overweight and obese groups. Older age and high level of low-density lipoprotein cholesterol were the independent risk factor for carotid plaque in four groups. Increased systolic blood pressure was an independent risk factor in the normal-weight, overweight, and obese groups; however, fasting plasma glucose was only significant in the normal-weight group. Thus, controlling the levels of low-density lipoprotein cholesterol, systolic blood pressure, and fasting plasma glucose is required to reduce carotid plaque risk.

  1. Micro-analysis of plaque fluid from single-site fasted plaque

    Energy Technology Data Exchange (ETDEWEB)

    Vogel, G.L.; Carey, C.M.; Chow, L.C.; Tatevossian, A. (American Dental Association Health Foundation, Gaithersburg, MD (USA))

    1990-06-01

    Despite the site-specific nature of caries, nearly all data on the concentration of ions relevant to the level of saturation of plaque fluid with respect to calcium phosphate minerals or enamel are from studies that used pooled samples. A procedure is described for the collection and analysis of inorganic ions relevant to these saturation levels in plaque fluid samples collected from a single surface on a single tooth. Various methods for examining data obtained by this procedure are described, and a mathematical procedure employing potential plots is recommended.

  2. Relation of cholesterol and lipoprotein parameters with carotid artery plaque characteristics: the Atherosclerosis Risk in Communities (ARIC) carotid MRI study.

    Science.gov (United States)

    Virani, Salim S; Catellier, Diane J; Pompeii, Lisa A; Nambi, Vijay; Hoogeveen, Ron C; Wasserman, Bruce A; Coresh, Josef; Mosley, Thomas H; Otvos, James D; Sharrett, A Richey; Boerwinkle, Eric; Ballantyne, Christie M

    2011-12-01

    There is a paucity of data regarding relations of apolipoproteins (apolipoprotein B [ApoB] and apolipoprotein A-1 [Apo A-1]), lipoprotein particle measures (low-density lipoprotein particle concentration [LDLp] and high-density lipoprotein particle concentration [HDLp]), and lipoprotein cholesterol measures (low-density lipoprotein cholesterol [LDL-C], non-high-density lipoprotein cholesterol [non-HDL-C], and high-density lipoprotein cholesterol [HDL-C]) with atherosclerotic plaque burden, plaque eccentricity, and lipid-rich core presence as a marker of high-risk plaques. Carotid artery magnetic resonance imaging was performed in 1670 Atherosclerosis Risk in Communities study participants. Vessel wall and lipid cores were measured; normalized wall index (NWI), standard deviation (SD) of wall thickness (measure of plaque eccentricity) were calculated; and lipid cores were detected in vessels with ≥ 1.5mm thickness. Fasting concentrations of cholesterol, ApoB and Apo A-1, and LDLp and HDLp were measured. Measures of plaque burden (carotid wall volume, wall thickness, and NWI) were positively associated with atherogenic cholesterol and lipoproteins (p < 0.05 for total cholesterol, LDL-C, non-HDL-C, ApoB, and LDLp), but not with HDL-C, Apo A-1, or HDLp. SD of wall thickness was associated with total cholesterol (p 0.01) and non-HDL-C (p 0.02). Although measures of atherogenic or anti-atherogenic cholesterol or lipoprotein were not individually associated with detection of a lipid-rich core, their ratios (total cholesterol/HDL-C, non-HDL-C/HDL-C, and LDLp/HDLp) were associated with lipid-rich core presence (p ≤ 0.05). Extent of carotid atherosclerosis is associated with atherogenic cholesterol and lipoproteins. Atherogenic/anti-atherogenic cholesterol or particle ratios were associated with presence of a detectable lipid-rich core. Published by Elsevier Ireland Ltd.

  3. Atherosclerotic plaque identification by virtual histology intravascular ultrasound in a rabbit abdominal aorta model of vulnerable plaque.

    Science.gov (United States)

    Lin, Qing-Fei; Luo, Yu-Kun; Zhao, Zi-Wen; Cai, Wei; Zhen, Xing-Chun; Chen, Liang-Long

    2013-11-01

    This study aimed to evaluate the utility of virtual histology intravascular ultrasound (VH-IVUS) for recognizing vulnerable plaque compared to histological pathological analysis. Four-month-old New Zealand rabbits (n = 16) were randomly divided into two groups: one fed a high-fat diet and subjected to balloon injury (experimental, n = 10) and one fed a high-fat diet alone (control, n = 6). Blood lipid profiles of overnight-fasted rabbits were measured at week 2 (beginning of study) and week 12 (end of study). At week 12, experimental group rabbits underwent IVUS under anaesthesia. Rabbits were sacrificed and a 5-cm segment of the abdominal aorta was removed. Arterial sections were subjected to pathological and immunohistochemical analyses. Serum lipid levels increased in all rabbits fed with high-fat diet, with low-density lipid cholesterol (LDL-C) levels increasing the most. Levels of six biomarkers (high sensitivity C-reactive protein, matrix metalloproteinase-3, interleukin [IL]-1, IL-10, tumour necrosis factor-α, and oxidized [ox]-LDL) showed no differences between the two groups at week 2, but were higher in the experimental group at week 12. A total of 276 atherosclerotic plaques in the experimental group were analysed. VH-IVUS had sensitivities of 87% and 92% for detection of noncalcified and calcified thin-cap fibroatheromas, respectively. VH-IVUS correctly identified 85% and 89% of noncalcified and calcified fibroatheromas, respectively. For detection of pathological intimal thickening, VH-IVUS showed a sensitivity of 79% and positive predictive value of 78%. Linear regression analysis showed a strong correlation between histology and VH-IVUS for the percent area of fibrous fibro-fatty tissue, necrotic calcified tissue, and confluent necrotic core. The intra-observer and inter-observer variability of the intimal and medial-adventitial boundaries was low. Endothelial injury followed by a high-fat diet in rabbits is a viable method for inducing

  4. Soluble amyloid beta levels are elevated in the white matter of Alzheimer's patients, independent of cortical plaque severity.

    Science.gov (United States)

    Collins-Praino, Lyndsey E; Francis, Yitshak I; Griffith, Erica Y; Wiegman, Anne F; Urbach, Jonathan; Lawton, Arlene; Honig, Lawrence S; Cortes, Etty; Vonsattel, Jean Paul G; Canoll, Peter D; Goldman, James E; Brickman, Adam M

    2014-08-17

    Alzheimer's disease (AD) is the most common neurodegenerative disease and the leading cause of dementia. In addition to grey matter pathology, white matter changes are now recognized as an important pathological feature in the emergence of the disease. Despite growing recognition of the importance of white matter abnormalities in the pathogenesis of AD, the causes of white matter degeneration are still unknown. While multiple studies propose Wallerian-like degeneration as the source of white matter change, others suggest that primary white matter pathology may be due, at least in part, to other mechanisms, including local effects of toxic Aβ peptides. In the current study, we investigated levels of soluble amyloid-beta (Aβ) in white matter of AD patients (n=12) compared with controls (n=10). Fresh frozen white matter samples were obtained from anterior (Brodmann area 9) and posterior (Brodmann area 1, 2 and 3) areas of post-mortem AD and control brains. ELISA was used to examine levels of soluble Aβ -42 and Aβ -40. Total cortical neuritic plaque severity rating was derived from individual ratings in the following areas of cortex: mid-frontal, superior temporal, pre-central, inferior parietal, hippocampus (CA1), subiculum, entorhinal cortex, transentorhinal cortex, inferior temporal, amygdala and basal forebrain. Compared with controls, AD samples had higher white matter levels of both soluble Aβ -42 and Aβ -40. While no regional white matter differences were found in Aβ -40, Aβ -42 levels were higher in anterior regions than in posterior regions across both groups. After statistically controlling for total cortical neuritic plaque severity, differences in both soluble Aβ -42 and Aβ -40 between the groups remained, suggesting that white matter Aβ peptides accumulate independent of overall grey matter fibrillar amyloid pathology and are not simply a reflection of overall amyloid burden. These results shed light on one potential mechanism through which

  5. Association of circulating omentin-1 level with arterial stiffness and carotid plaque in type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Yoo Hye

    2011-11-01

    Full Text Available Abstract Background Adipokines contribute directly to the atherosclerotic process, connecting metabolic disorders such as obesity and diabetes to cardiovascular disease. Omentin-1 is a recently discovered novel adipokine, so data about the relationship of this adipokine to vascular health in type 2 diabetes is limited. Methods We enrolled 60 people with type 2 diabetes, with or without carotid plaque, and 30 participants with normal glucose tolerance. We measured serum omentin-1, high-sensitivity C-reactive protein (hsCRP levels, and the homeostasis model assessment of insulin resistance (HOMA-IR, as well as other cardiovascular risk factors. Vascular health was assessed by brachial ankle pulse wave velocity (baPWV and carotid intima-media thickness (IMT. Results Serum omentin-1 levels were significantly decreased in type 2 diabetes patients compared to normal glucose controls and was further reduced in type 2 diabetes patients with carotid plaque compared to those without carotid plaque. Multiple stepwise regression analysis showed that age, systolic blood pressure, history of use of statins, angiotensin receptor blockers or angiotensin-converting enzyme inhibitors, and serum omentin-1 level were independent factors determining baPWV in people with type 2 diabetes (r2 = 0.637. Furthermore, in multivariate logistic regression analysis, circulating omentin-1 level was an independent decisive factor for the presence of carotid plaque in type 2 diabetes patients, even after adjusting for age, gender, body mass index, systolic blood pressure, fasting blood glucose, low density lipoprotein cholesterol, and history of smoking and medication (odds ratio, 0.621; 95% confidence interval, 0.420-0.919; P = 0.017. Conclusions Circulating omentin-1 level was independently correlated with arterial stiffness and carotid plaque in type 2 diabetes, even after adjusting for other cardiovascular risk factors and detailed medication history.

  6. Dosimetric Benefit of a New Ophthalmic Radiation Plaque

    Energy Technology Data Exchange (ETDEWEB)

    Marwaha, Gaurav, E-mail: marwahg2@ccf.org [Department of Radiation Oncology, Taussig Cancer Center, Cleveland Clinic Foundation, Cleveland, Ohio (United States); Cleveland Clinic Foundation, Cleveland, Ohio (United States); Wilkinson, Allan [Department of Radiation Oncology, Taussig Cancer Center, Cleveland Clinic Foundation, Cleveland, Ohio (United States); Cleveland Clinic Foundation, Cleveland, Ohio (United States); Bena, James [Department of Quantitative Health Sciences, Cleveland Clinic Foundation, Cleveland, Ohio (United States); Cleveland Clinic Foundation, Cleveland, Ohio (United States); Macklis, Roger [Department of Radiation Oncology, Taussig Cancer Center, Cleveland Clinic Foundation, Cleveland, Ohio (United States); Cleveland Clinic Foundation, Cleveland, Ohio (United States); Singh, Arun D. [Department of Radiation Oncology, Taussig Cancer Center, Cleveland Clinic Foundation, Cleveland, Ohio (United States); Department of Ophthalmic Oncology, Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio (United States); Cleveland Clinic Foundation, Cleveland, Ohio (United States)

    2012-12-01

    Purpose: To determine whether the computed dosimetry of a new ophthalmic plaque, EP917, when compared with the standard Collaborative Ocular Melanoma Study (COMS) plaques, could reduce radiation exposure to vision critical structures of the eye. Methods and Materials: One hundred consecutive patients with uveal melanoma treated with COMS radiation plaques between 2007 and 2010 were included in this study. These treatment plans were generated with the use of Bebig Plaque Simulator treatment-planning software, both for COMS plaques and for EP917 plaques using I-125. Dose distributions were calculated for a prescription of 85 Gy to the tumor apex. Doses to the optic disc, opposite retina, lens, and macula were obtained, and differences between the 2 groups were analyzed by standard parametric methods. Results: When compared with the COMS plaques, the EP917 plaques used fewer radiation seeds by an average difference of 1.94 (P<.001; 95% confidence interval [CI], -2.8 to -1.06) and required less total strength of radiation sources by an average of 17.74 U (air kerma units) (P<.001; 95% CI, -20.16 to -15.32). The total radiation doses delivered to the optic disc, opposite retina, and macula were significantly less by 4.57 Gy, 0.50 Gy, and 11.18 Gy, respectively, with the EP917 plaques vs the COMS plaques. Conclusion: EP917 plaques deliver less overall radiation exposure to critical vision structures than COMS treatment plaques while still delivering the same total therapeutic dose to the tumor.

  7. Prophylaxis for infective endocarditis: antibiotic sensitivity of dental plaque.

    OpenAIRE

    MacFarlane, T W; McGowan, D A; Hunter, K; MacKenzie, D.

    1983-01-01

    The antibiotic sensitivity pattern of bacteria isolated from bacteraemia after dental extraction was compared with that of bacteria isolated from dental plaque samples from the same patient. The results supported the current practice of using penicillin and erythromycin empirically for prophylaxis. The prediction of the most appropriate antibiotic for prophylaxis using dental plaque samples was most accurate when the minimum inhibitory concentration (MIC) of plaque isolates were used. It appe...

  8. Aberrant myelinated neurites in the anterior horns of a patient with amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    Troost, D.; Louwerse, E. S.; de Jong, J. M.; van Leersum, G. S.; van Raalte, J. A.

    1989-01-01

    A case of amyotrophic lateral sclerosis revealed the classical pathologic features of ALS, i.e. neuronal loss in the anterior horns and pyramidal tract degeneration. In addition to the pathological hallmarks of Alzheimer's disease, senile plaques, neurofibrillary tangles and granulovacuolar changes

  9. Plaque-removal efficacy of four types of dental floss.

    Science.gov (United States)

    Terézhalmy, Géza T; Bartizek, Robert D; Biesbrock, Aaron R

    2008-02-01

    Effective plaque removal is essential for gingival health, and dental floss is used to augment plaque removal achieved with a toothbrush. This randomized, controlled, examiner-masked, five-period crossover study examined plaque removal in 25 subjects following single use with an American Dental Association reference manual toothbrush alone and in combination with four floss products: three traditional (unwaxed, woven, and shred-resistant) and one powered flosser. Plaque was scored before and after brushing for 1 minute. The Rustogi modified Navy plaque index was used to focus scores on tooth areas contacted during the proper use of dental floss. Mean plaque reductions (baseline minus postbrushing) in floss contact areas were as follows: 0.181 with the toothbrush alone; 0.228, 0.217, and 0.210 for the toothbrush in combination with the three traditional flosses, unwaxed, woven, and shred-resistant, respectively; and 0.252 for the toothbrush plus powered flosser. No statistically significant differences were found between the three traditional floss treatments. All four floss treatments showed greater (P plaque removal than the toothbrush alone. Mean plaque removal with the powered flosser combination was greater than for the woven combination and shred-resistant combination (both P toothbrush removed plaque significantly better than the toothbrush alone. Among floss types, there was evidence of superiority for the powered flosser, but there were no significant treatment differences between the three traditional floss products.

  10. Stress analysis of fracture of atherosclerotic plaques: crack propagation modeling.

    Science.gov (United States)

    Rezvani-Sharif, Alireza; Tafazzoli-Shadpour, Mohammad; Kazemi-Saleh, Davood; Sotoudeh-Anvari, Maryam

    2017-08-01

    Traditionally, the degree of luminal obstruction has been used to assess the vulnerability of atherosclerotic plaques. However, recent studies have revealed that other factors such as plaque morphology, material properties of lesion components and blood pressure may contribute to the fracture of atherosclerotic plaques. The aim of this study was to investigate the mechanism of fracture of atherosclerotic plaques based on the mechanical stress distribution and fatigue analysis by means of numerical simulation. Realistic models of type V plaques were reconstructed based on histological images. Finite element method was used to determine mechanical stress distribution within the plaque. Assuming that crack propagation initiated at the sites of stress concentration, crack propagation due to pulsatile blood pressure was modeled. Results showed that crack propagation considerably changed the stress field within the plaque and in some cases led to initiation of secondary cracks. The lipid pool stiffness affected the location of crack formation and the rate and direction of crack propagation. Moreover, increasing the mean or pulse pressure decreased the number of cycles to rupture. It is suggested that crack propagation analysis can lead to a better recognition of factors involved in plaque rupture and more accurate determination of vulnerable plaques.

  11. Association of Streptococcus with Plaque Type of Psoriasis

    Directory of Open Access Journals (Sweden)

    Mohammad Akram Hossain

    2015-05-01

    Full Text Available Background: Guttate psoriasis has a well-known association with streptococcal throat infections, but the effects of these infections in patients with chronic plaque type of psoriasis remains to be evaluated. In Bangladesh several studies were done on psoriasis but no data about association between streptococcal throat infection and plaque type psoriasis are available so far. Considering the co-morbidities of psoriasis patients, it might be justifiable to find out the events that provoke the initiation or exacerbation of psoriatic disease process. Objective: To observe the association of streptococcus with plaque type of psoriasis. Materials and Methods: This observational study was conducted in the department of Dermatology and Venereology, Bangabandhu Sheikh Mujib Medical University, Dhaka. Forty seven patients clinically and histopathologically diagnosed as having plaque psoriasis were selected as cases and patients with skin diseases other than psoriasis were selected as controls. Results: In this study majority of subjects (55% were diagnosed as chronic plaque psoriasis. Among the subjects with guttate flare of chronic plaque psoriasis 64.2% gave a positive history of sore throat. ASO titer was raised (>200 IU/mL in 28 (59.5% patients of chronic plaque psoriasis and 7 (17.9% patients of non-psoriatic respondents. The difference between two groups was significant (p0.05. Conclusion: This study shows that streptococcal throat infections are associated with plaque psoriasis and early treatment of throat infections may be beneficial for plaque type of psoriasis patients.

  12. In vivo detection of amyloid plaques by gadolinium-stained MRI can be used to demonstrate the efficacy of an anti-amyloid immunotherapy

    Directory of Open Access Journals (Sweden)

    Mathieu D. Santin

    2016-03-01

    Full Text Available Extracellular deposition of β amyloid plaques is an early event associated to Alzheimer's disease. Here we have used in vivo gadolinium-stained high resolution (29*29*117µm3 MRI to follow-up in a longitudinal way individual amyloid plaques in APP/PS1 mice and evaluate the efficacy of a new immunotherapy (SAR255952 directed against protofibrillar and fibrillary forms of Aβ. APP/PS1 mice were treated for 5 months between the age of 3.5 and 8.5 months. SAR255952 reduced amyloid load in 8.5-month-old animals, but not in 5.5-month animals compared to mice treated with a control antibody (DM4. Histological evaluation confirmed the reduction of amyloid load and revealed a lower density of amyloid plaques in 8.5-month SAR255952-treated animals. The longitudinal follow-up of individual amyloid plaques by MRI revealed that plaques that were visible at 5.5 months were still visible at 8.5 months in both SAR255952 and DM4-treated mice. This suggests that the amyloid load reduction induced by SAR255952 is related to a slowing down in the formation of new plaques rather than to the clearance of already formed plaques.

  13. Lipid peroxidation and decomposition--conflicting roles in plaque vulnerability and stability.

    Science.gov (United States)

    Parthasarathy, Sampath; Litvinov, Dmitry; Selvarajan, Krithika; Garelnabi, Mahdi

    2008-05-01

    The low density lipoprotein (LDL) oxidation hypothesis has generated considerable interest in oxidative stress and how it might affect atherosclerosis. However, the failure of antioxidants, particularly vitamin E, to affect the progression of the disease in humans has convinced even staunch supporters of the hypothesis to take a step backwards and reconsider alternatives. Preponderant evidence for the hypothesis came from animal antioxidant intervention studies. In this review we point out basic differences between animal and human atherosclerosis development and suggest that human disease starts where animal studies end. While initial oxidative steps in the generation of early fatty streak lesions might be common, the differences might be in the steps involved in the decomposition of peroxidized lipids into aldehydes and their further oxidation into carboxylic acids. We suggest that these steps may not be amenable to attenuation by antioxidants and antioxidants might actually counter the stabilization of plaque by preventing the formation of carboxylic acids which are anti-inflammatory in nature. The formation of such dicarboxylic acids may also be conducive to plaque stabilization by trapping calcium. We suggest that agents that would prevent the decomposition of lipid peroxides and promote the formation and removal of lipid hydroxides, such as paraoxonase (PON 1) or apo A1/high density lipoprotein (HDL) might be more conducive to plaque regression.

  14. A Wnt-planar polarity pathway instructs neurite branching by restricting F-actin assembly through endosomal signaling

    Science.gov (United States)

    Chen, Chun-Hao; Liao, Chien-Po

    2017-01-01

    Spatial arrangement of neurite branching is instructed by both attractive and repulsive cues. Here we show that in C. elegans, the Wnt family of secreted glycoproteins specify neurite branching sites in the PLM mechanosensory neurons. Wnts function through MIG-1/Frizzled and the planar cell polarity protein (PCP) VANG-1/Strabismus/Vangl2 to restrict the formation of F-actin patches, which mark branching sites in nascent neurites. We find that VANG-1 promotes Wnt signaling by facilitating Frizzled endocytosis and genetically acts in a common pathway with arr-1/β-arrestin, whose mutation results in defective PLM branching and F-actin patterns similar to those in the Wnt, mig-1 or vang-1 mutants. On the other hand, the UNC-6/Netrin pathway intersects orthogonally with Wnt-PCP signaling to guide PLM branch growth along the dorsal-ventral axis. Our study provides insights for how attractive and repulsive signals coordinate to sculpt neurite branching patterns, which are critical for circuit connectivity. PMID:28384160

  15. MAGNETIC FIELD INFLUENCE ON NGF-STIMULATED NEURITE OUTGROWTH IN PC-12 CELLS: EFFECT OF PAINT FUMES

    Science.gov (United States)

    MAGNETIC FIELD INFLUENCE ON NGF-STIMULATED NEURITE OUTGROWTH IN PC-12 CELLS: EFFECT OF PAINT FUMES. C. F. Blackman1, D. E. House2*, S. G. Benane3*, A. Ubeda4, M.A. TrilIo4. 1 National Health and Environmental Effects Research Laboratory, EPA,Research Triangle Park, North Caro...

  16. Ultrafast optical recording reveals distinct capsaicin-induced ion dynamics along single nociceptive neurite terminals in vitro

    Science.gov (United States)

    Goldstein, Robert H.; Katz, Ben; Lev, Shaya; Binshtok, Alexander M.

    2017-07-01

    Pain signals are detected by terminals of nociceptive peripheral fibers situated among the keratinocytes and epithelial cells. Despite being key structures for pain-related stimuli detection and transmission, little is known about the functional organization of terminals. This is mainly due to their minute size, rendering them largely inaccessible by conventional experimental approaches. Here, we report the implementation of an ultrafast optical recording approach for studying cultured neurite terminals, which are readily accessible for assay manipulations. Using this approach, we were able to study capsaicin-induced calcium and sodium dynamics in the nociceptive processes, at a near-action potential time resolution. The approach was sensitive enough to detect differences in latency, time-to-peak, and amplitude of capsaicin-induced ion transients along the terminal neurites. Using this approach, we found that capsaicin evokes distinctive calcium signals along the neurite. At the terminal, the signal was insensitive to voltage-gated sodium channel blockers, and showed slower kinetics and smaller signal amplitudes, compared with signals that were measured further up the neurite. These latter signals were mainly abolished by sodium channel blockers. We propose this ultrafast optical recording approach as a model for studying peripheral terminal signaling, forming a basis for studying pain mechanisms in normal and pathological states.

  17. Neurite outgrowth induced by a synthetic peptide ligand of neural cell adhesion molecule requires fibroblast growth factor receptor activation

    DEFF Research Database (Denmark)

    Rønn, L C; Doherty, P; Holm, A

    2000-01-01

    The neural cell adhesion molecule NCAM is involved in axonal outgrowth and target recognition in the developing nervous system. In vitro, NCAM-NCAM binding has been shown to induce neurite outgrowth, presumably through an activation of fibroblast growth factor receptors (FGFRs). We have recently...

  18. Neurite Mistargeting and Inverse Order of Intraretinal Vascular Plexus Formation Precede Subretinal Vascularization in Vldlr Mutant Mice.

    Directory of Open Access Journals (Sweden)

    Verity Johnson

    Full Text Available In the retina blood vessels are required to support a high metabolic rate, however, uncontrolled vascular growth can lead to impaired vision and blindness. Subretinal vascularization (SRV, one type of pathological vessel growth, occurs in retinal angiomatous proliferation and proliferative macular telangiectasia. In these diseases SRV originates from blood vessels within the retina. We use mice with a targeted disruption in the Vldl-receptor (Vldlr gene as a model to study SRV with retinal origin. We find that Vldlr mRNA is strongly expressed in the neuroretina, and we observe both vascular and neuronal phenotypes in Vldlr-/- mice. Unexpectedly, horizontal cell (HC neurites are mistargeted prior to SRV in this model, and the majority of vascular lesions are associated with mistargeted neurites. In Foxn4-/- mice, which lack HCs and display reduced amacrine cell (AC numbers, we find severe defects in intraretinal capillary development. However, SRV is not suppressed in Foxn4-/-;Vldlr-/- mice, which reveals that mistargeted HC neurites are not required for vascular lesion formation. In the absence of VLDLR, the intraretinal capillary plexuses form in an inverse order compared to normal development, and subsequent to this early defect, vascular proliferation is increased. We conclude that SRV in the Vldlr-/- model is associated with mistargeted neurites and that SRV is preceded by altered retinal vascular development.

  19. Manipulation of gene expression in the mammalian nervous system: application in the study of neurite outgrowth and neuroregeneration related proteins

    NARCIS (Netherlands)

    Gispen, W.H.; Holtmaat, A.J.G.D.; Oestreicher, A.B.; Verhaagen, J.

    1998-01-01

    A fundamental issue in neurobiology entails the study of the formation of neuronal connections and their potential to regenerate following injury. In recent years, an expanding number of gene families has been identified involved in different aspects of neurite outgrowth and regeneration. These

  20. Turning Death to Growth: Hematopoietic Growth Factors Promote Neurite Outgrowth through MEK/ERK/p53 Pathway.

    Science.gov (United States)

    Gao, Mei; Zhao, Li-Ru

    2017-11-08

    Stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) are the essential hematopoietic growth factors to control hematopoiesis. However, the role of SCF and G-CSF in the central nervous system remains poorly understood. Here, we have demonstrated the involvement of MEK/ERK/p53 signaling in SCF + G-CSF-enhanced neurite extension. Cortical neurons dissected from embryonic rat brains were seeded onto the membranes of transwell inserts, and neurite outgrowth was determined by using both the neurite outgrowth quantification assay kit and immunostaining of β III tubulin. Quantitative RT-PCR and western blotting were used for determining gene and protein expression of ERK and p53, respectively. p53 small interfering RNA (siRNAs) were introduced into neurons for examining the involvement of p53 in SCF + G-CSF-mediated neurite outgrowth. We observed that both SCF and G-CSF alone increased activation of MEK/ERK and gene expression of p53, while SCF + G-CSF synergistically activated the MEK/ERK signaling and upregulated p53 expression. MEK specific inhibitors (PD98059 and U0126) blocked the SCF + G-CSF-increased ERK phosphorylation and p53 gene and protein expression, and the MEK specific inhibitors also eliminated the SCF + G-CSF-promoted neurite outgrowth. p53 siRNAs knocked down the SCF + G-CSF-elevated p53 protein and prevented the SCF + G-CSF-enhanced neurite outgrowth. These findings suggest that activation of MEK/ERK/p53 signaling is required for SCF + G-CSF-promoted neurite outgrowth. Through the pro-apoptotic pathway of the MEK/ERK/p53, SCF + G-CSF turns neuronal fate from apoptotic commitment toward neural network generation. This observation provides novel insights into the putative role of SCF + G-CSF in supporting generation of neural connectivity during CNS development and in brain repair under pathological or neurodegenerative conditions.

  1. Pleurotus giganteus (Berk.) Karunarathna & K.D. Hyde: Nutritional value and in vitro neurite outgrowth activity in rat pheochromocytoma cells.

    Science.gov (United States)

    Phan, Chia-Wei; Wong, Wei-Lun; David, Pamela; Naidu, Murali; Sabaratnam, Vikineswary

    2012-07-19

    Drugs dedicated to alleviate neurodegenerative diseases like Parkinson's and Alzheimer's have always been associated with debilitating side effects. Medicinal mushrooms which harness neuropharmacological compounds offer a potential possibility for protection against such diseases. Pleurotus giganteus (formerly known as Panus giganteus) has been consumed by the indigenous people in Peninsular Malaysia for many years. Domestication of this wild mushroom is gaining popularity but to our knowledge, medicinal properties reported for this culinary mushroom are minimal. The fruiting bodies P. giganteus were analysed for its nutritional values. Cytotoxicity of the mushroom's aqueous and ethanolic extracts towards PC12, a rat pheochromocytoma cell line was assessed by using 3-[4,5-dimethythiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Neurite outgrowth stimulation assay was carried out with nerve growth factor (NGF) as control. To elucidate signaling mechanisms involved by mushroom extract-induced neurite outgrowth, treatment of specific inhibitor for MEK/ERK and PI3K signalling pathway was carried out. The fruiting bodies of P. giganteus were found to have high carbohydrate, dietary fibre, potassium, phenolic compounds and triterpenoids. Both aqueous and ethanolic extracts induced neurite outgrowth of PC12 cells in a dose- and time-dependant manner with no detectable cytotoxic effect. At day 3, 25 μg/ml of aqueous extract and 15 μg/ml of ethanolic extract showed the highest percentage of neurite-bearing cells, i.e. 31.7 ± 1.1% and 33.3 ± 0.9%; respectively. Inhibition treatment results suggested that MEK/ERK and PI3K/Akt are responsible for neurite outgrowth of PC12 cells stimulated by P. giganteus extract. The high potassium content (1345.7 mg/100 g) may be responsible for promoting neurite extension, too. P. giganteus contains bioactive compounds that mimic NGF and are responsible for neurite stimulation. Hence, this mushroom may be

  2. The Lipid-Rich Plaque Study of vulnerable plaques and vulnerable patients: Study design and rationale.

    Science.gov (United States)

    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.

  3. Mechanism of ceroid formation in atherosclerotic plaque: in situ studies using a combination of Raman and fluorescence spectroscopy.

    Science.gov (United States)

    Haka, Abigail S; Kramer, John R; Dasari, Ramachandra R; Fitzmaurice, Maryann

    2011-01-01

    Accumulation of the lipid-protein complex ceroid is a characteristic of atherosclerotic plaque. The mechanism of ceroid formation has been extensively studied, because the complex is postulated to contribute to plaque irreversibility. Despite intensive research, ceroid deposits are defined through their fluorescence and histochemical staining properties, while their composition remains unknown. Using Raman and fluorescence spectral microscopy, we examine the composition of ceroid in situ in aorta and coronary artery plaque. The synergy of these two types of spectroscopy allows for identification of ceroid via its fluorescence signature and elucidation of its chemical composition through the acquisition of a Raman spectrum. In accordance with in vitro predictions, low density lipoprotein (LDL) appears within the deposits primarily in its peroxidized form. The main forms of modified LDL detected in both coronary artery and aortic plaques are peroxidation products from the Fenton reaction and myeloperoxidase-hypochlorite pathway. These two peroxidation products occur in similar concentrations within the deposits and represent ∼40 and 30% of the total LDL (native and peroxidized) in the aorta and coronary artery deposits, respectively. To our knowledge, this study is the first to successfully employ Raman spectroscopy to unravel a metabolic pathway involved in disease pathogenesis: the formation of ceroid in atherosclerotic plaque.

  4. Modeling of Experimental Atherosclerotic Plaque Delamination.

    Science.gov (United States)

    Leng, Xiaochang; Chen, Xin; Deng, Xiaomin; Sutton, Michael A; Lessner, Susan M

    2015-12-01

    A cohesive zone model (CZM) approach is applied to simulate atherosclerotic plaque delamination experiments in mouse abdominal aorta specimens. A three-dimensional finite element model is developed for the experiments. The aortic wall is treated as a fiber-reinforced, highly deformable, incompressible material, and the Holzapfel-Gasser-Ogden (HGO) model is adopted for the aortic bulk material behavior. Cohesive elements are placed along the plaque-media interface along which delamination occurs. The 3D specimen geometry is created based on images from the experiments and certain simplifying approximations. A set of HGO and CZM parameter values is determined based on values suggested in the literature and through matching simulation predictions of the load vs. load-point displacement curve with experimental measurements for one loading-delamination-unloading cycle. Using this set of parameter values, simulation predictions for four other loading-delamination-unloading cycles are obtained, which show good agreement with experimental measurements. The findings of the current study demonstrate the applicability of the CZM approach in arterial tissue failure simulations.

  5. Interaction of new antidepressants with sigma-1 receptor chaperones and their potentiation of neurite outgrowth in PC12 cells.

    Science.gov (United States)

    Ishima, Tamaki; Fujita, Yuko; Hashimoto, Kenji

    2014-03-15

    The sigma-1 receptor chaperone located in the endoplasmic reticulum (ER) may be implicated in the mechanistic action of some antidepressants. The present study was undertaken to examine whether new antidepressant drugs interact with the sigma-1 receptor chaperone. First, we examined the effects of selective serotonin reuptake inhibitors (SSRIs) (fluvoxamine, paroxetine, sertraline, citalopram and escitalopram), serotonin and noradrenaline reuptake inhibitors (SNRIs) (duloxetine, venlafaxine, milnacipran), and mirtazapine, a noradrenaline and specific serotonergic antidepressant (NaSSA), on [(3)H](+)-pentazocine binding to rat brain membranes. Then, we examined the effects of these drugs on nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells. The order of potency for drugs at the sigma-1 receptor chaperone was as follows: fluvoxamine>sertraline>fluoxetine>escitalopram>citalopram>paroxetine>duoxetine. Venlafaxine, milnacipran, and mirtazapine showed very weak affinity for this chaperone. Furthermore, fluvoxamine, fluoxetine, escitalopram, and mirtazapine significantly potentiated NGF-induced neurite outgrowth in cell assays, and the effects of all these drugs, excluding mirtazapine, were antagonized by NE-100, a selective antagonist of the sigma-1 receptor chaperone. Moreover, the effects of fluvoxamine and fluoxetine on neurite outgrowth were also antagonized by sertraline, indicating that sertraline may be an antagonist at the sigma-1 receptor chaperone. The effect of mirtazapine on neurite outgrowth was antagonized by the selective 5-hydroxytryptamine1A receptor antagonist WAY-100635. These findings suggest that activation at the sigma-1 receptor chaperone may be involved in the action of some SSRIs, such as fluvoxamine, fluoxetine and escitalopram. In contrast, mirtazapine independently potentiated neurite outgrowth in PC12 cells, indicating that this beneficial effect may mediate its pharmacological effect. Copyright © 2014 Elsevier B.V. All

  6. Lysophosphatidylinositol causes neurite retraction via GPR55, G13 and RhoA in PC12 cells.

    Directory of Open Access Journals (Sweden)

    Yutaro Obara

    Full Text Available GPR55 was recently identified as a putative receptor for certain cannabinoids, and lysophosphatidylinositol (LPI. Recently, the role of cannabinoids as GPR55 agonists has been disputed by a number of reports, in part, because studies investigating GPR55 often utilized overexpression systems, such as the GPR55-overexpressing HEK293 cells, which make it difficult to deduce the physiological role of endogenous GPR55. In the present study, we found that PC12 cells, a neural model cell line, express endogenous GPR55, and by using these cells, we were able to examine the role of endogenous GPR55. Although GPR55 mRNA and protein were expressed in PC12 cells, neither CB(1 nor CB(2 mRNA was expressed in these cells. GPR55 was predominantly localized on the plasma membrane in undifferentiated PC12 cells. However, GPR55 was also localized in the growth cones or the ruffled border in differentiated PC12 cells, suggesting a potential role for GPR55 in the regulation of neurite elongation. LPI increased intracellular Ca(2+ concentration and RhoA activity, and induced ERK1/2 phosphorylation, whereas endogenous and synthetic cannabinoids did not, thereby suggesting that cannabinoids are not GPR55 agonists. LPI also caused neurite retraction in a time-dependent manner accompanied by the loss of neurofilament light chain and redistribution of actin in PC12 cells differentiated by NGF. This LPI-induced neurite retraction was found to be G(q-independent and G(13-dependent. Furthermore, inactivation of RhoA function via C3 toxin and GPR55 siRNA knockdown prevented LPI-induced neurite retraction. These results suggest that LPI, and not cannabinoids, causes neurite retraction in differentiated PC12 cells via a GPR55, G(13 and RhoA signaling pathway.

  7. Neurite outgrowth mediated by translation elongation factor eEF1A1: a target for antiplatelet agent cilostazol.

    Directory of Open Access Journals (Sweden)

    Kenji Hashimoto

    Full Text Available Cilostazol, a type-3 phosphodiesterase (PDE3 inhibitor, has become widely used as an antiplatelet drug worldwide. A recent second Cilostazol Stroke Prevention Study demonstrated that cilostazol is superior to aspirin for prevention of stroke after an ischemic stroke. However, its precise mechanisms of action remain to be determined. Here, we report that cilostazol, but not the PDE3 inhibitors cilostamide and milrinone, significantly potentiated nerve growth factor (NGF-induced neurite outgrowth in PC12 cells. Furthermore, specific inhibitors for the endoplasmic reticulum protein inositol 1,4,5-triphosphate (IP(3 receptors and several common signaling pathways (PLC-γ, PI3K, Akt, p38 MAPK, and c-Jun N-terminal kinase (JNK, and the Ras/Raf/ERK/MAPK significantly blocked the potentiation of NGF-induced neurite outgrowth by cilostazol. Using a proteomics analysis, we identified that levels of eukaryotic translation elongation factor eEF1A1 protein were significantly increased by treatment with cilostazol, but not cilostamide, in PC12 cells. Moreover, the potentiating effects of cilostazol on NGF-induced neurite outgrowth were significantly antagonized by treatment with eEF1A1 RNAi, but not the negative control of eEF1A1. These findings suggest that eEF1A1 and several common cellular signaling pathways might play a role in the mechanism of cilostazol-induced neurite outgrowth. Therefore, agents that can increase the eEF1A1 protein may have therapeutic relevance in diverse conditions with altered neurite outgrowth.

  8. Functional role of a specific ganglioside in neuronal migration and neurite outgrowth

    Directory of Open Access Journals (Sweden)

    Mendez-Otero R.

    2003-01-01

    Full Text Available Cell migration occurs extensively during mammalian brain development and persists in a few regions in the adult brain. Defective migratory behavior of neurons is thought to be the underlying cause of several congenital disorders. Knowledge of the dynamics and molecular mechanisms of neuronal movement could expand our understanding of the normal development of the nervous system as well as help decipher the pathogenesis of neurological developmental disorders. In our studies we have identified and characterized a specific ganglioside (9-O-acetyl GD3 localized to the membrane of neurons and glial cells that is expressed in regions of cell migration and neurite outgrowth in the developing and adult rat nervous system. In the present article we review our findings that demonstrate the functional role of this molecule in neuronal motility.

  9. Fundamental Elements in Autism: From Neurogenesis and Neurite Growth to Synaptic Plasticity

    Science.gov (United States)

    Gilbert, James; Man, Heng-Ye

    2017-01-01

    Autism spectrum disorder (ASD) is a set of neurodevelopmental disorders with a high prevalence and impact on society. ASDs are characterized by deficits in both social behavior and cognitive function. There is a strong genetic basis underlying ASDs that is highly heterogeneous; however, multiple studies have highlighted the involvement of key processes, including neurogenesis, neurite growth, synaptogenesis and synaptic plasticity in the pathophysiology of neurodevelopmental disorders. In this review article, we focus on the major genes and signaling pathways implicated in ASD and discuss the cellular, molecular and functional studies that have shed light on common dysregulated pathways using in vitro, in vivo and human evidence. Highlights Autism spectrum disorder (ASD) has a prevalence of 1 in 68 children in the United States.ASDs are highly heterogeneous in their genetic basis.ASDs share common features at the cellular and molecular levels in the brain.Most ASD genes are implicated in neurogenesis, structural maturation, synaptogenesis and function. PMID:29209173

  10. Rit contributes to neurite outgrowth triggered by the alpha subunit of Go.

    Science.gov (United States)

    Kim, Seung Hyun; Kim, Soyeon; Ghil, Sung Ho

    2008-03-26

    Heterotrimeric GTP-binding protein transduce signals initiated by a variety of hormones and neurotransmitters. Go, a member of the Go/Gi family, is the most abundant heterotrimeric GTP-binding protein in nervous tissues and has been implicated in neuronal differentiation. The mechanism by which Go modulates neuronal differentiation has not been, however, fully elucidated. Here, we identified small GTPase Rit as an interacting partner of the alpha-subunit of Go (Goalpha). The biochemical characterizations of Goalpha::Rit interaction revealed that Rit is a candidate downstream effector for Goalpha. Furthermore, dominant negative Rit inhibited Goalpha-induced neurite outgrowth and Erk phosphorylation in Neuro2a cells. These results suggest that Rit may be involved in the signaling pathway for Goalpha-mediated neuronal differentiation.

  11. Release of mineral ions in dental plaque following acid production.

    Science.gov (United States)

    Tanaka, M; Margolis, H C

    1999-03-01

    The release of appreciable amounts of calcium, phosphate and fluoride found in whole plaque into the plaque-fluid phase, following bacterial acid production, can potentially reduce the driving force for tooth demineralization. However, limited information is available on this topic, particularly on the release of fluoride. This study sought to determine the change in calcium, phosphate and fluoride concentrations in plaque fluid after sucrose exposure. 48 h overnight-fasted supragingival plaque samples were collected from all tooth surfaces (with the exception of the lower lingual anterior teeth) of one half of an individual mouth, following a 1 min water rinse. Plaque samples were then collected from the other half of the same mouth, following a 292 mM sucrose rinse. Plaque fluid was isolated by centrifugation and analysed for total calcium and phosphate (ion chromatography) and for free fluoride (ion-specific electrode). Samples were collected from seven individuals. Following sucrose exposure, plaque-fluid pH decreased significantly from 6.5+/- 0.3 to 5.4+/-0.2; calcium concentrations (mmol/l) also increased significantly (p phosphate concentrations in plaque fluid, however, did not increase significantly after sucrose exposure: mean concentrations (mmol/l) of fluoride after the water and sucrose rinses were 0.006+/-0.003 and 0.005+/-0.002, respectively, and mean phosphate concentrations (mmol/l) were 11.0+/-2.0 and 12.0+/-3.0, respectively. When results were expressed per wet plaque weight, phosphate concentrations were also found to increase significantly. The same trends were observed when additional plaque samples were treated in vitro with sucrose: fluoride-ion activity did not increase in plaque under in vivo-like conditions.

  12. Plaque removal efficacy of Colgate 360 toothbrush: A clinical study

    Directory of Open Access Journals (Sweden)

    Nageshwar Iyer

    2016-01-01

    Full Text Available Aim: The aim of this clinical study was to confirm the plaque removal efficacy of the Colgate 360 Whole Mouth Clean Toothbrush. Study Design: This was a single-center, monadic, case-controlled study with the 7 days duration. Materials and Methods: A total of eighty participants (56 male and 24 female aged between 18 and 45 years with a minimum of 20 permanent teeth (excluding the third molars without any prosthetic crowns and an initial plaque score of minimum 1.5 as determined by Modified Quigley-Hein Plaque Index (1970 participated in the study. There were two dropouts during the study duration, one male and one female. The participants were instructed to brush for 1 min, after which plaque index was recorded again. They were then instructed to brush their teeth twice a day for 1 min with the assigned toothbrush (Colgate 360 Whole Mouth Clean Toothbrush and a commercially available fluoride toothpaste for the next 7 days. On the 7 th day, all the participants were recalled for follow-up and plaque examination. The plaque index scores (pre- and post-brushing were recorded, tabulated, and analyzed statistically. Results: The mean plaque indices reduced after brushing both on day 1 and day 7. There was also a reduction in mean plaque indices from day 1 to day 7. All these reductions were statistically significant (P < 0.001. The reduction in plaque scores was independent of the gender of the participants however female participants showed lower scores as compared to male participants (P < 0.001. Conclusion: The present study demonstrated a significant reduction in plaque scores with the use of Colgate 360 Whole Mouth Clean Soft Toothbrush throughout the study period. Continued use resulted in a further significant reduction in plaque scores irrespective of the gender of participants.

  13. Moringa oleifera with promising neuronal survival and neurite outgrowth promoting potentials.

    Science.gov (United States)

    Hannan, Md Abdul; Kang, Ji-Young; Mohibbullah, Md; Hong, Yong-Ki; Lee, Hyunsook; Choi, Jae-Suk; Choi, In Soon; Moon, Il Soo

    2014-02-27

    Moringa oleifera Lam. (Moringaceae) by virtue of its high nutritional as well as ethnomedical values has been gaining profound interest both in nutrition and medicinal research. The leaf of this plant is used in ayurvedic medicine to treat paralysis, nervous debility and other nerve disorders. In addition, research evidence also suggests the nootropic as well as neuroprotective roles of Moringa oleifera leaf in animal models. The aim of the present study was to evaluate the effect of Moringa oleifera leaf in the primary hippocampal neurons regarding its neurotrophic and neuroprotective properties. The primary culture of embryonic hippocampal neurons was incubated with the ethanol extract of Moringa oleifera leaf (MOE). After an indicated time, cultures were either stained directly with a lipophilic dye, DiO, or fixed and immunolabeled to visualize the neuronal morphology. Morphometric analyses for neurite maturation and synaptogenesis were performed using Image J software. Neuronal viability was evaluated using trypan blue exclusion and lactate dehydrogenase assays. MOE promoted neurite outgrowth in a concentration-dependent manner with an optimal concentration of 30 μg/mL. As a very initial effect, MOE significantly promoted the earlier stages of neuronal differentiation. Subsequently, MOE significantly increased the number and length of dendrites, the length of axon, and the number and length of both dendrite and axonal branches, and eventually facilitated synaptogenesis. The β-carotene, one major compound of MOE, promoted neuritogensis, but the increase was not comparable with the effect of MOE. In addition, MOE supported neuronal survival by protecting neurons from naturally occurring cell death in vitro. Our findings indicate that MOE promotes axodendritic maturation as well as provides neuroprotection suggesting a promising pharmacological importance of this nutritionally and ethnomedically important plant for the well-being of nervous system. Copyright

  14. Low gray scale values of computerized images of carotid plaques associated with increased levels of triglyceride-rich lipoproteins and with increased plaque lipid content

    DEFF Research Database (Denmark)

    Grønholdt, Marie-Louise M.; Nordestgaard, Børge; Weibe, Britt M.

    1997-01-01

    Relatioin between low gray scale values in computerized images of carotid plaques and 1) plasma levels of triglyceride-rich lipoproteins and 2) plaque lipid content......Relatioin between low gray scale values in computerized images of carotid plaques and 1) plasma levels of triglyceride-rich lipoproteins and 2) plaque lipid content...

  15. Frontotemporal dementia with parkinsonism linked to chromosome 17 with the MAPT R406W mutation presenting with a broad distribution of abundant senile plaques.

    Science.gov (United States)

    Ishida, Chiho; Kobayashi, Katsuji; Kitamura, Tatsuru; Ujike, Hiroshi; Iwasa, Kazuo; Yamada, Masahito

    2015-02-01

    We report the autopsy results of a patient with familial dementia who was diagnosed as having frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) with an R406W mutation in the microtubule-associated protein tau (MAPT) gene. This patient showed Alzheimer's disease (AD)-like clinical manifestations from the age of 59, with reduced β-amyloid1-42 (Aβ42 ) and elevated total and phosphorylated tau levels in the cerebrospinal fluid. He did not present with any apparent parkinsonism throughout the disease course. His autopsy at age 73 showed atrophy and neurodegeneration in many brain regions, particularly in the antero-medial temporal cortex and hippocampus, followed by the frontal lobes, with abundant neurofibrillary tangles. In addition, a diffuse distribution of Aβ-positive senile plaques, including many neuritic plaques, was observed and classified as stage C according to the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria. These results suggest that analyzing of the MAPT gene is essential for diagnosing familial dementia, even if amyloid markers such as Aβ42 in the cerebrospinal fluid and amyloid imaging are positive, or if neuropathological findings indicate a diagnosis of AD. © 2014 Japanese Society of Neuropathology.

  16. Uptake of 11C-choline in mouse atherosclerotic plaques

    DEFF Research Database (Denmark)

    Laitinen, Iina E K; Luoto, Pauliina; Någren, Kjell

    2010-01-01

    The purpose of this study was to explore the feasibility of (11)C-choline in the assessment of the degree of inflammation in atherosclerotic plaques.......The purpose of this study was to explore the feasibility of (11)C-choline in the assessment of the degree of inflammation in atherosclerotic plaques....

  17. Complement factor C5a induces atherosclerotic plaque disruptions

    Science.gov (United States)

    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

  18. Vulnerable plaque detection: The role of 18-fluorine ...

    African Journals Online (AJOL)

    Positron emission tomography computed tomography (PET-CT) is a combined functional and structural multi modality imaging tool that can be utilized to detect vulnerable and atherosclerotic plaques. In this study we observe the prevalence of active and calcified plaques in selected arteries during whole-body 18F-FDG ...

  19. Chronic plaque psoriasis | Luba | South African Family Practice

    African Journals Online (AJOL)

    Chronic plaque psoriasis, the most common form of psoriasis, is a papulosquamous disease defined by erythematous plaques with a silvery scale. The diagnosis usually is clinical, but occasionally a biopsy is necessary. Psoriasis affects 0.6 to 4.8 percent of the U.S. population, and about 30 percent of affected patients have ...

  20. Characterization of bacteriophage communities and CRISPR profiles from dental plaque.

    Science.gov (United States)

    Naidu, Mayuri; Robles-Sikisaka, Refugio; Abeles, Shira R; Boehm, Tobias K; Pride, David T

    2014-06-30

    Dental plaque is home to a diverse and complex community of bacteria, but has generally been believed to be inhabited by relatively few viruses. We sampled the saliva and dental plaque from 4 healthy human subjects to determine whether plaque was populated by viral communities, and whether there were differences in viral communities specific to subject or sample type. We found that the plaque was inhabited by a community of bacteriophage whose membership was mostly subject-specific. There was a significant proportion of viral homologues shared between plaque and salivary viromes within each subject, suggesting that some oral viruses were present in both sites. We also characterized Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) in oral streptococci, as their profiles provide clues to the viruses that oral bacteria may be able to counteract. While there were some CRISPR spacers specific to each sample type, many more were shared across sites and were highly subject specific. Many CRISPR spacers matched viruses present in plaque, suggesting that the evolution of CRISPR loci may have been specific to plaque-derived viruses. Our findings of subject specificity to both plaque-derived viruses and CRISPR profiles suggest that human viral ecology may be highly personalized.

  1. Red fluorescent dental plaque: An indicator of oral disease?

    NARCIS (Netherlands)

    Volgenant, C.M.C.

    2016-01-01

    Oral diseases are worldwide the most common diseases, with dental caries and periodontal inflammatory diseases as most frequently occurring diseases. Both are strongly associated with dental plaque, which is the mass of bacteria (biofilm) that grows on surfaces in the mouth. Some dental plaque

  2. Atherosclerotic carotid plaque assessment with multidetector computed tomography angiography

    NARCIS (Netherlands)

    T.T. de Weert (Thomas)

    2009-01-01

    textabstractThis thesis evaluates the role of MDCT angiography in 1) the depiction of atherosclerotic disease and subsequent luminal stenosis in the arteries that supplies the brain with blood, and 2) the assessment of atherosclerotic plaque features that have been related to plaque vulnerability.

  3. Bacterial colonization of psoriasis plaques. Is it relevant?

    Directory of Open Access Journals (Sweden)

    Eva Marcus

    2011-08-01

    Full Text Available Bacterial colonization was investigated retrospectively in patients with plaque psoriasis (n=98 inpatient treatments, n=73 patients. At least one pathogen was found in 46% of all cases. Staphylococcus aureus was the most frequent bacterium. Bacterial colonization of psoriasis plaques could be relevant in individual cases.

  4. Lysophosphatidic acid triggers mast cell-driven atherosclerotic plaque destabilization by increasing vascular inflammation.

    NARCIS (Netherlands)

    Bot, M.; , van, Berkel T.J.C.

    2013-01-01

    Lysophosphatidic acid (LPA), a bioactive lysophospholipid, accumulates in the atherosclerotic plaque. It has the capacity to activate mast cells, which potentially exacerbates plaque progression. In this study, we thus aimed to investigate whether LPA contributes to plaque destabilization by

  5. Collagenase matrix metalloproteinase-8 expressed in atherosclerotic carotid plaques is associated with systemic cardiovascular outcome

    NARCIS (Netherlands)

    Peeters, W.; Moll, F.L.; Vink, A.; Spek, P.J. van der; Kleijn, D.P.V. de; Vries, J.-P.P.M. de; Verheijen, J.H.; Newby, A.C.; Pasterkamp, G.

    2011-01-01

    Aims Atherosclerotic plaque rupture and subsequent thrombus formation are the major cause of acute cardiovascular events. Local plaque markers may facilitate detection of the vulnerable plaque and help identify the patient at risk for cardiovascular events. Matrix metalloproteinases (MMPs) are

  6. Compressive mechanical properties of atherosclerotic plaques - Indentation test to characterise the local anisotropic behaviour

    NARCIS (Netherlands)

    C.-K. Chai (Chen-Ket); L. Speelman (Lambert); C.W.J. Oomens (Cees); F.P.T. Baaijens (Frank)

    2014-01-01

    textabstractAccurate material models and associated parameters of atherosclerotic plaques are crucial for reliable biomechanical plaque prediction models. These biomechanical models have the potential to increase our understanding of plaque progression and failure, possibly improving risk assessment

  7. Imaging Modalities to Identity Inflammation in an Atherosclerotic Plaque.

    Science.gov (United States)

    Goel, Sunny; Miller, Avraham; Agarwal, Chirag; Zakin, Elina; Acholonu, Michael; Gidwani, Umesh; Sharma, Abhishek; Kulbak, Guy; Shani, Jacob; Chen, On

    2015-01-01

    Atherosclerosis is a chronic, progressive, multifocal arterial wall disease caused by local and systemic inflammation responsible for major cardiovascular complications such as myocardial infarction and stroke. With the recent understanding that vulnerable plaque erosion and rupture, with subsequent thrombosis, rather than luminal stenosis, is the underlying cause of acute ischemic events, there has been a shift of focus to understand the mechanisms that make an atherosclerotic plaque unstable or vulnerable to rupture. The presence of inflammation in the atherosclerotic plaque has been considered as one of the initial events which convert a stable plaque into an unstable and vulnerable plaque. This paper systemically reviews the noninvasive and invasive imaging modalities that are currently available to detect this inflammatory process, at least in the intermediate stages, and discusses the ongoing studies that will help us to better understand and identify it at the molecular level.

  8. Imaging Modalities to Identity Inflammation in an Atherosclerotic Plaque

    Directory of Open Access Journals (Sweden)

    Sunny Goel

    2015-01-01

    Full Text Available Atherosclerosis is a chronic, progressive, multifocal arterial wall disease caused by local and systemic inflammation responsible for major cardiovascular complications such as myocardial infarction and stroke. With the recent understanding that vulnerable plaque erosion and rupture, with subsequent thrombosis, rather than luminal stenosis, is the underlying cause of acute ischemic events, there has been a shift of focus to understand the mechanisms that make an atherosclerotic plaque unstable or vulnerable to rupture. The presence of inflammation in the atherosclerotic plaque has been considered as one of the initial events which convert a stable plaque into an unstable and vulnerable plaque. This paper systemically reviews the noninvasive and invasive imaging modalities that are currently available to detect this inflammatory process, at least in the intermediate stages, and discusses the ongoing studies that will help us to better understand and identify it at the molecular level.

  9. Automated coronary CT angiography plaque-lumen segmentation

    Science.gov (United States)

    Cline, Harvey E.; Krishnan, Karthik; Napel, Sandy; Rubin, Geoffrey D.; Turner, Wesley D.; Avila, Ricardo S.

    2009-02-01

    We are investigating the feasibility of a computer-aided detection (CAD) system to assist radiologists in diagnosing coronary artery disease in ECG gated cardiac multi-detector CT scans having calcified plaque. Coronary artery stenosis analysis is challenging if calcified plaque or the iodinated blood pool hides viable lumen. The research described herein provides an improved presentation to the radiologist by removing obscuring calcified plaque and blood pool. The algorithm derives a Gaussian estimate of the point spread function (PSF) of the scanner responsible for plaque blooming by fitting measured CTA image profiles. An initial estimate of the extent of calcified plaque is obtained from the image evidence using a simple threshold. The Gaussian PSF estimate is then convolved with the initial plaque estimate to obtain an estimate of the extent of the blooming artifact and this plaque blooming image is subtracted from the CT image to obtain an image largely free of obscuring plaque. In a separate step, the obscuring blood pool is suppressed using morphological operations and adaptive region growing. After processing by our algorithm, we are able to project the segmented plaque-free lumen to form synthetic angiograms free from obstruction. We can also analyze the coronary arteries with vessel tracking and centerline extraction to produce cross sectional images for measuring lumen stenosis. As an additional aid to radiologists, we also produce plots of calcified plaque and lumen cross-sectional area along selected blood vessels. The method was validated using digital phantoms and actual patient data, including in one case, a validation against the results of a catheter angiogram.

  10. Biomarkers for the prediction of acute ongoing arterial plaque rupture

    Directory of Open Access Journals (Sweden)

    Guo YL

    2013-07-01

    Full Text Available Yuan-Lin Guo, Jian-Jun Li Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China Abstract: Acute coronary syndrome (ACS is the main cause of mortality for coronary artery disease (CAD. Accordingly, earlier detection and diagnosis might be a key point for reducing the mortality in patients with ACS. One promising strategy is biomarker measurement in patients with ACS. Biomarkers are generally considered to be plasma measurements of molecules, proteins, or enzymes that provide independent diagnostic and prognostic values that can reflect underlying disease state and condition, especially repeated measurements. Nowadays, the most widely used biomarkers to identify or predict ACS are high sensitivity C-reactive protein (hs-CRP and high sensitivity troponin T/I (hs-TnT/I. The aim of the present review was principally to summarize recent evidence regarding some new biomarkers by which we could directly predict acute ongoing arterial plaque rupture, which may help to identify at-risk patients earlier than hs-CRP or hs-TnT/I. Keywords: matrix metalloproteinase-9, lipoprotein associated phospholipase A2, myeloperoxidase, soluble lectin-like oxidized low-density lipoprotein receptor-1, pregnancy-associated plasma protein A, placental growth factor, acute coronary syndrome

  11. The effects of microenvironment on the redifferentiation of regenerating neurones: neurite architecture, acetylcholine receptors and Ca2+ channel distribution.

    Science.gov (United States)

    Spira, M E; Zeldes, D; Hochner, B; Dormann, A

    1987-09-01

    Severed adult neurones, which are capable of regrowth, encounter different microenvironments from those encountered during development. Moreover, adult neurones may respond in a different manner from developing neurones to the same environmental cues. Thus, the recovery of the integrative and transmission capabilities (which depend on the neuronal architecture, passive and active membrane properties, and synaptic receptor distribution) by a regenerating adult neurone may not be complete. In the present review, we examine several aspects of the outcome of the interaction between the microenvironment and regrowing neurones using the cockroach giant interneurones (GINs) as a model system. We demonstrate that whereas extrinsic cues govern the morphological redifferentiation and distribution of synaptic receptors, the distribution of voltage-dependent Ca2+ channels is to a large extent determined by intrinsic factors. The pathway of regrowth and the architecture of regenerating GINs were studied by examination of intracellularly stained fibres. The environments provided by the connectives and ganglia are different. The elongating sprouts in the connective appeared as smooth cylinders. Within the ganglionic domain, the main longitudinal sprouts emitted neurites which extended and branched into the neuropile. The local cues for branching of neurites were eliminated by freezing and thawing of the ganglia prior to the arrival of the growing tips. The failure to extend neurites under these conditions is attributed to the elimination of extrinsic signals for morphological redifferentiation of the fibres, since the same fibres emit neurites in anterior ganglia which have not been subjected to freezing and thawing. The distribution of acetylcholine receptors (AChRs) on the GINs was mapped by ionophoretic application of ACh. In both the intact and regenerating GINs receptors were located only on the neurites. Freezing and thawing of a ganglion eliminated the local signals for

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

    Science.gov (United States)

    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

  13. 3D Isotropic MR Culprit Plaque Visualization of Carotid Plaque Edema and Hemorrhage with Motion Sensitized Blood Suppression

    DEFF Research Database (Denmark)

    Søvsø Szocska Hansen, Esben; Pedersen, Steen Fjord; Bloch, Lars Ø.

    2014-01-01

    hemorrhage and plaque edema may represent advanced stages of atherosclerosis[1, 2]. In this study, we present a novel multi-contrast 3D motion sensitized black-blood CMR imaging sequence, which detects both plaque edema and hemorrhage with positive contrast. Subjects and Methods The 3D imaging sequence...... formatting in all three dimensions was possible to provide a comprehensive and exhaustive evaluation of the vessel wall. For the symptomatic carotid artery plaque, hyperintensive signal intensity was detected with a signal-to-noise ratio (SNR) that was significantly higher compared to the vessel wall...... proximal to the bifurcation (43.36±8.01 versus 16.91±3.49, respectively P plaque compared to the proximal carotid vessel wall was 26.45±4.60 and CNR plaque...

  14. Validation of automatically classified magnetic resonance images for carotid plaque compositional analysis.

    Science.gov (United States)

    Clarke, Sharon E; Beletsky, Vadim; Hammond, Robert R; Hegele, Robert A; Rutt, Brian K

    2006-01-01

    MRI may be used for noninvasive assessment of atherosclerotic lesions; however, MRI evaluation of plaque composition requires validation against an accepted reference standard, such as the American Heart Association (AHA) lesion grade, defined by histopathological examination. Forty-eight carotid endarterectomy specimen cross-sections had AHA lesion grade determined histopathologically and were concurrently imaged using combinations of 8 MRI contrast weightings in vitro. A maximum likelihood classification algorithm generated MRI "maps" of plaque components, and an AHA lesion grade was assigned correspondingly. Additional analyses compared classification accuracy obtained with a commonly used set of magnetic resonance contrast weightings [proton density (PDw), T1 (T1w), and partial T2 (T2w)] to accuracy obtained with the combination of PDw, T1w, and diffusion-weighted (Dw) contrast. For the 8-contrast combination, the sensitivities for fibrous tissue, necrotic core, calcification, and hemorrhage detection were 83%, 67%, 86%, and 77%, respectively. The corresponding specificities were 81%, 78%, 99%, and 97%. Good agreement (79%) between magnetic resonance and histopathology for AHA classification was achieved. For the PDw, T1w, and Dw combination, the overall classification accuracy was insignificantly different at 78%, whereas the overall classification accuracy using PDw, T1w, and partial T2w contrast weightings was significantly lower at 67%. This study provides proof-of-principle that the composition of atherosclerotic plaques determined by automated classification of high-resolution ex vivo MRI accurately reflects lesion composition defined by histopathological examination.

  15. Icariin improves memory impairment in Alzheimer's disease model mice (5xFAD) and attenuates amyloid β-induced neurite atrophy.

    Science.gov (United States)

    Urano, Takuya; Tohda, Chihiro

    2010-11-01

    Essential therapeutic drugs for Alzheimer's disease (AD) have not been developed. Since the neuritic atrophy leading to synaptic losses is one of the critical causes of memory impairment in AD, the effects of several constituents in tonic herbal medicines on neuritic atrophy and memory deficits have been studied. The present study investigated the effects of icariin, a main constituent in Epimedii Herba, a well known tonic crude drug, in an in vitro AD model and transgenic mouse AD model (5xFAD). Amyloid β(1-42)-induced atrophies of axons and dendrites were restored by post-treatment with icariin in rat cortical neurons. Administration of icariin for 8 days (p.o.) improved spatial memory impairment in 5xFAD mice. These novel findings suggest that icariin may improve memory dysfunction in AD and have a potential to extend neurites even when amyloid β-induced neurite atrophy has already occurred. Copyright © 2010 John Wiley & Sons, Ltd.

  16. Atherosclerotic Plaque Destabilization in Mice: A Comparative Study.

    Directory of Open Access Journals (Sweden)

    Helene Hartwig

    Full Text Available Atherosclerosis-associated diseases are the main cause of mortality and morbidity in western societies. The progression of atherosclerosis is a dynamic process evolving from early to advanced lesions that may become rupture-prone vulnerable plaques. Acute coronary syndromes are the clinical manifestation of life-threatening thrombotic events associated with high-risk vulnerable plaques. Hyperlipidemic mouse models have been extensively used in studying the mechanisms controlling initiation and progression of atherosclerosis. However, the understanding of mechanisms leading to atherosclerotic plaque destabilization has been hampered by the lack of proper animal models mimicking this process. Although various mouse models generate atherosclerotic plaques with histological features of human advanced lesions, a consensus model to study atherosclerotic plaque destabilization is still lacking. Hence, we studied the degree and features of plaque vulnerability in different mouse models of atherosclerotic plaque destabilization and find that the model based on the placement of a shear stress modifier in combination with hypercholesterolemia represent with high incidence the most human like lesions compared to the other models.

  17. Vulnerable atherosclerotic plaque detection by resonance Raman spectroscopy

    Science.gov (United States)

    Liu, Cheng-hui; Boydston-White, Susie; Weisberg, Arel; Wang, Wubao; Sordillo, Laura A.; Perotte, Adler; Tomaselli, Vincent P.; Sordillo, Peter P.; Pei, Zhe; Shi, Lingyan; Alfano, Robert R.

    2016-12-01

    A clear correlation has been observed between the resonance Raman (RR) spectra of plaques in the aortic tunica intimal wall of a human corpse and three states of plaque evolution: fibrolipid plaques, calcified and ossified plaques, and vulnerable atherosclerotic plaques (VPs). These three states of atherosclerotic plaque lesions demonstrated unique RR molecular fingerprints from key molecules, rendering their spectra unique with respect to one another. The vibrational modes of lipids, cholesterol, carotenoids, tryptophan and heme proteins, the amide I, II, III bands, and methyl/methylene groups from the intrinsic atherosclerotic VPs in tissues were studied. The salient outcome of the investigation was demonstrating the correlation between RR measurements of VPs and the thickness measurements of fibrous caps on VPs using standard histopathology methods, an important metric in evaluating the stability of a VP. The RR results show that VPs undergo a structural change when their caps thin to 66 μm, very close to the 65-μm empirical medical definition of a thin cap fibroatheroma plaque, the most unstable type of VP.

  18. Urease and Dental Plaque Microbial Profiles in Children.

    Science.gov (United States)

    Morou-Bermudez, Evangelia; Rodriguez, Selena; Bello, Angel S; Dominguez-Bello, Maria G

    2015-01-01

    Urease enzymes produced by oral bacteria generate ammonia, which can have a significant impact on the oral ecology and, consequently, on oral health. To evaluate the relationship of urease with dental plaque microbial profiles in children as it relates to dental caries, and to identify the main contributors to this activity. 82 supragingival plaque samples were collected from 44 children at baseline and one year later, as part of a longitudinal study on urease and caries in children. DNA was extracted; the V3-V5 region of the 16S rRNA gene was amplified and sequenced using 454 pyrosequencing. Urease activity was measured using a spectrophotometric assay. Data were analyzed with Qiime. Plaque urease activity was significantly associated with the composition of the microbial communities of the dental plaque (Baseline P = 0.027, One Year P = 0.012). The bacterial taxa whose proportion in dental plaque exhibited significant variation by plaque urease levels in both visits were the family Pasteurellaceae (Baseline Pplaque. Further studies are needed to establish the role of urease-associated bacteria in the acid/base homeostasis of the dental plaque, and in the development and prediction of dental caries in children.

  19. Clinical plaque removing efficacy of a new power toothbrush.

    Science.gov (United States)

    Ernst, C P; Nauth, C; Willershausen, B; Warren, P R

    1998-09-01

    To evaluate the effect of adding a pulsating bristle action to the established oscillating/rotating action of the Braun Oral-B Ultra Plaque Remover (D9) on plaque removal. Plaque removal was evaluated using the modified Quigley-Hein Plaque Index in a double blind randomized, crossover study involving 32 healthy volunteers without any dental training. After 2 weeks use of the D9 during which time subjects received training in its use, subjects abstained from oral hygiene for 48 hours. They were then assessed for plaque after which they brushed their teeth using an experimental toothbrush randomly set to either the D9 oscillating/rotating action or to the new 3D action with an additional pulsating movement of the brush head in the direction of the long axis of the bristles. After brushing, plaque was again evaluated. Following a further 2 weeks of normal home use of the D9, subjects returned and the procedure was repeated using the brush set in the second mode. Both toothbrush actions were found to be effective at removing plaque from all sites and surfaces in the mouth. The 3D action was consistently more effective than that of the D9, the difference being statistically significant for the whole mouth, the upper jaw, the lingual surfaces and for all interproximal sites, in particular in the upper jaw.

  20. Myelin-associated Glycoprotein Interacts with Neurons via a Sialic Acid Binding Site at ARG118 and a Distinct Neurite Inhibition Site

    OpenAIRE

    Tang, Song; Shen, Ying Jing; DeBellard, Maria Elena; Mukhopadhyay, Gitali; Salzer, James L.; Crocker, Paul R.; Filbin, Marie T.

    1997-01-01

    Inhibitory components in myelin are largely responsible for the lack of regeneration in the mammalian CNS. Myelin-associated glycoprotein (MAG), a sialic acid binding protein and a component of myelin, is a potent inhibitor of neurite outgrowth from a variety of neurons both in vitro and in vivo. Here, we show that MAG's sialic acid binding site is distinct from its neurite inhibitory activity. Alone, sialic acid–dependent binding of MAG to neurons is insufficient to effect inhibition of axon...

  1. Neurite outgrowth stimulatory effects of culinary-medicinal mushrooms and their toxicity assessment using differentiating Neuro-2a and embryonic fibroblast BALB/3T3

    OpenAIRE

    Phan, Chia-Wei; David, Pamela; Naidu, Murali; Wong, Kah-Hui; Sabaratnam, Vikineswary

    2013-01-01

    Background Mushrooms are not only regarded as gourmet cuisine but also as therapeutic agent to promote cognition health. However, little toxicological information is available regarding their safety. Therefore, the aim of this study was to screen selected ethno-pharmacologically important mushrooms for stimulatory effects on neurite outgrowth and to test for any cytotoxicity. Methods The stimulatory effect of mushrooms on neurite outgrowth was assessed in differentiating mouse neuroblastoma (...

  2. Identification of NCAM-binding peptides promoting neurite outgrowth via a heterotrimeric G-protein-coupled pathway

    DEFF Research Database (Denmark)

    Hansen, Raino Kristian; Christensen, Claus; Korshunova, Irina

    2007-01-01

    and ENFIN11) were confirmed to bind to F3I-F3II of NCAM by surface plasmon resonance. The peptides induced neurite outgrowth in primary cerebellar neurons and PC12E2 cells, but had no apparent neuroprotective properties. NCAM is known to activate different intracellular pathways, including signaling through......A combinatorial library of undecapeptides was produced and utilized for the isolation of peptide binding to the fibronectin type 3 modules (F3I-F3II) of the neural cell adhesion molecule (NCAM). The isolated peptides were sequenced and produced as dendrimers. Two of the peptides (denoted ENFIN2...... the fibroblast growth factor receptor, the Src-related non-receptor tyrosine kinase Fyn, and heterotrimeric G-proteins. Interestingly, neurite outgrowth stimulated by ENFIN2 and ENFIN11 was independent of signaling through fibroblast growth factor receptor and Fyn, but could be inhibited with pertussis toxin...

  3. Morphine enhances HIV-1SF162-mediated neuron death and delays recovery of injured neurites.

    Science.gov (United States)

    Masvekar, Ruturaj R; El-Hage, Nazira; Hauser, Kurt F; Knapp, Pamela E

    2014-01-01

    HIV-1 enters the CNS soon after initial systemic infection; within the CNS parenchyma infected and/or activated perivascular macrophages, microglia and astrocytes release viral and cellular toxins that drive secondary toxicity in neurons and other cell types. Our previous work has largely modeled HIV-neuropathology using the individual viral proteins Tat or gp120, with murine striatal neurons as targets. To model disease processes more closely, the current study uses supernatant from HIV-1-infected cells. Supernatant from HIV-1SF162-infected differentiated-U937 cells (HIV+sup) was collected and p24 level was measured by ELISA to assess the infection. Injection drug abuse is a significant risk factor for HIV-infection, and opiate drug abusers show increased HIV-neuropathology, even with anti-retroviral treatments. We therefore assessed HIV+sup effects on neuronal survival and neurite growth/pruning with or without concurrent exposure to morphine, an opiate that preferentially acts through µ-opioid receptors. Effects of HIV+sup ± morphine were assessed on neuronal populations, and also by time-lapse imaging of individual cells. HIV+sup caused dose-dependent toxicity over a range of p24 levels (10-500 pg/ml). Significant interactions occurred with morphine at lower p24 levels (10 and 25 pg/ml), and GSK3β was implicated as a point of convergence. In the presence of glia, selective neurotoxic measures were significantly enhanced and interactions with morphine were also augmented, perhaps related to a decreased level of BDNF. Importantly, the arrest of neurite growth that occurred with exposure to HIV+sup was reversible unless neurons were continuously exposed to morphine. Thus, while reducing HIV-infection levels may be protective, ongoing exposure to opiates may limit recovery. Opiate interactions observed in this HIV-infective environment were similar, though not entirely concordant, with Tat/gp120 interactions reported previously, suggesting unique interactions

  4. Morphine enhances HIV-1SF162-mediated neuron death and delays recovery of injured neurites.

    Directory of Open Access Journals (Sweden)

    Ruturaj R Masvekar

    Full Text Available HIV-1 enters the CNS soon after initial systemic infection; within the CNS parenchyma infected and/or activated perivascular macrophages, microglia and astrocytes release viral and cellular toxins that drive secondary toxicity in neurons and other cell types. Our previous work has largely modeled HIV-neuropathology using the individual viral proteins Tat or gp120, with murine striatal neurons as targets. To model disease processes more closely, the current study uses supernatant from HIV-1-infected cells. Supernatant from HIV-1SF162-infected differentiated-U937 cells (HIV+sup was collected and p24 level was measured by ELISA to assess the infection. Injection drug abuse is a significant risk factor for HIV-infection, and opiate drug abusers show increased HIV-neuropathology, even with anti-retroviral treatments. We therefore assessed HIV+sup effects on neuronal survival and neurite growth/pruning with or without concurrent exposure to morphine, an opiate that preferentially acts through µ-opioid receptors. Effects of HIV+sup ± morphine were assessed on neuronal populations, and also by time-lapse imaging of individual cells. HIV+sup caused dose-dependent toxicity over a range of p24 levels (10-500 pg/ml. Significant interactions occurred with morphine at lower p24 levels (10 and 25 pg/ml, and GSK3β was implicated as a point of convergence. In the presence of glia, selective neurotoxic measures were significantly enhanced and interactions with morphine were also augmented, perhaps related to a decreased level of BDNF. Importantly, the arrest of neurite growth that occurred with exposure to HIV+sup was reversible unless neurons were continuously exposed to morphine. Thus, while reducing HIV-infection levels may be protective, ongoing exposure to opiates may limit recovery. Opiate interactions observed in this HIV-infective environment were similar, though not entirely concordant, with Tat/gp120 interactions reported previously, suggesting

  5. The effect of gallium nitride on long-term culture induced aging of neuritic function in cerebellar granule cells.

    Science.gov (United States)

    Chen, Chi-Ruei; Young, Tai-Horng

    2008-04-01

    Gallium nitride (GaN) has been developed for a variety of microelectronic and optical applications due to its unique electric property and chemical stability. In the present study, n-type and p-type GaN were used as substrates to culture cerebellar granule neurons to examine the effect of GaN on cell response for a long-term culture period. It was found that GaN could rapidly induce cultured neurons to exhibit a high phosphorylated Akt level after 20h of incubation. It was assumed that the anti-apoptotic effect of Akt phosphorylation could be correlated with cell survival, neurite growth and neuronal function for up to 35 days of incubation. Morphological studies showed GaN induced larger neuronal aggregates and neurite fasciculation to exhibit a dense fiber network after 8 days of incubation. Western blot analysis and immunocytochemical characterization showed that GaN still exhibited the expression of neurite growth and function, such as high levels of GAP-43, synapsin I and synaptophysin even after 35 days of incubation. In addition, survival of cerebellar granule neurons on GaN was improved by the analysis of lactate dehydrogenase (LDH) release from damaged cells. These results indicated that neuronal connections were formed on GaN by a gradual process from Akt activation and cell aggregation to develop neurite growth, fasciculation and function. Therefore, GaN offers a good model system to identify a well-characterized pattern of neuronal behavior for a long-term culture period, consistent with the development of a neurochip requiring the integration of biological system and semiconductor material.

  6. Atherosclerotic plaque detection by confocal Brillouin and Raman microscopies

    Science.gov (United States)

    Meng, Zhaokai; Basagaoglu, Berkay; Yakovlev, Vladislav V.

    2015-02-01

    Atherosclerosis, the development of intraluminal plaque, is a fundamental pathology of cardiovascular system and remains the leading cause of morbidity and mortality worldwide. Biomechanical in nature, plaque rupture occurs when the mechanical properties of the plaque, related to the morphology and viscoelastic properties, are compromised, resulting in intraluminal thrombosis and reduction of coronary blood flow. In this report, we describe the first simultaneous application of confocal Brillouin and Raman microscopies to ex-vivo aortic wall samples. Such a non-invasive, high specific approach allows revealing a direct relationship between the biochemical and mechanical properties of atherosclerotic tissue.

  7. Clear Plaque Mutants of Lactococcal Phage TP901-1

    DEFF Research Database (Denmark)

    Kot, Witold; Kilstrup, Mogens; Vogensen, Finn K.

    2016-01-01

    We report a method for obtaining turbid plaques of the lactococcal bacteriophage TP901-1 and its derivative TP901-BC1034. We have further used the method to isolate clear plaque mutants of this phage. Analysis of 8 such mutants that were unable to lysogenize the host included whole genome...... protein involved in the DNA binding. The conclusion is that cI is the only gene involved in clear plaque formation i.e. the CI protein is the determining factor for the lysogenic pathway and its maintenance in the lactococcal phage TP901-1....

  8. Thiocyanate supplementation decreases atherosclerotic plaque in mice expressing human myeloperoxidase

    DEFF Research Database (Denmark)

    Morgan, P E; Laura, R P; Maki, R A

    2015-01-01

    the curve (AUC). Mean serum SCN(-) concentrations were elevated in the supplemented mice (200-320 μM) relative to controls (plaque areas at sacrifice were 26% lower in the SCN(-)-supplemented mice compared with controls (P = 0.0417), but plaque morphology...... was not appreciably altered. Serum MPO levels steadily increased in mice on the high-fat diet, however, comparison of SCN(-)-supplemented versus control mice showed no significant changes in MPO protein, cholesterol, or triglyceride levels; thiol levels were decreased in supplemented mice at one time-point. Plaque...

  9. Rab35 promotes the recruitment of Rab8, Rab13 and Rab36 to recycling endosomes through MICAL-L1 during neurite outgrowth

    Directory of Open Access Journals (Sweden)

    Hotaka Kobayashi

    2014-08-01

    Full Text Available Small GTPase Rab35 is an important molecular switch for endocytic recycling that regulates various cellular processes, including cytokinesis, cell migration, and neurite outgrowth. We previously showed that active Rab35 promotes nerve growth factor (NGF-induced neurite outgrowth of PC12 cells by recruiting MICAL-L1, a multiple Rab-binding protein, to Arf6-positive recycling endosomes. However, the physiological significance of the multiple Rab-binding ability of MICAL-L1 during neurite outgrowth remained completely unknown. Here we report that Rab35 and MICAL-L1 promote the recruitment of Rab8, Rab13, and Rab36 to Arf6-positive recycling endosomes during neurite outgrowth. We found that Rab35 functions as a master Rab that determines the intracellular localization of MICAL-L1, which in turn functions as a scaffold for Rab8, Rab13, and Rab36. We further showed by functional ablation experiments that each of these downstream Rabs regulates neurite outgrowth in a non-redundant manner downstream of Rab35 and MICAL-L1, e.g. by showing that knockdown of Rab36 inhibited recruitment of Rab36-specific effector JIP4 to Arf6-positive recycling endosomes, and caused inhibition of neurite outgrowth without affecting accumulation of Rab8 and Rab13 in the same Arf6-positive area. Our findings suggest the existence of a novel mechanism that recruits multiple Rab proteins at the Arf6-positive compartment by MICAL-L1.

  10. Non-obese diabetic mice rapidly develop dramatic sympathetic neuritic dystrophy: a new experimental model of diabetic autonomic neuropathy.

    Science.gov (United States)

    Schmidt, Robert E; Dorsey, Denise A; Beaudet, Lucie N; Frederick, Kathy E; Parvin, Curtis A; Plurad, Santiago B; Levisetti, Matteo G

    2003-11-01

    To address the pathogenesis of diabetic autonomic neuropathy, we have examined the sympathetic nervous system in non-obese diabetic (NOD) and streptozotocin (STZ)-induced diabetic mice, two models of type 1 diabetes, and the db/db mouse, a model of type 2 diabetes. After only 3 to 5 weeks of diabetes, NOD mice developed markedly swollen axons and dendrites ("neuritic dystrophy") in the prevertebral superior mesenteric and celiac ganglia (SMG-CG), similar to the pathology described in diabetic STZ- and BBW-rat and man. Comparable changes failed to develop in the superior cervical ganglia of the NOD mouse or in the SMG-CG of non-diabetic NOD siblings. STZ-induced diabetic mice develop identical changes, although at a much slower pace and to a lesser degree than NOD mice. NOD-SCID mice, which are genetically identical to NOD mice except for the absence of T and B cells, do not develop diabetes or neuropathology comparable to diabetic NOD mice. However, STZ-treated NOD-SCID mice develop severe neuritic dystrophy, evidence against an exclusively autoimmune pathogenesis for autonomic neuropathy in this model. Chronically diabetic type 2 db/db mice fail to develop neuritic dystrophy, suggesting that hyperglycemia alone may not be the critical and sufficient element. The NOD mouse appears to be a valuable model of diabetic sympathetic autonomic neuropathy with unambiguous, rapidly developing neuropathology which corresponds closely to the characteristic pathology of other rodent models and man.

  11. Protective Effects of Rosa damascena and Its Active Constituent on Aβ(25–35-Induced Neuritic Atrophy

    Directory of Open Access Journals (Sweden)

    Suresh Awale

    2011-01-01

    Full Text Available Dementia is a clinical syndrome characterized by multiple cognitive deficits and causes progressive neurodegeneration leading eventually to death. The incidence of dementia is increasing worldwide with the increase in ageing population. However, no effective treatment is available yet. It has been hypothesized that drugs activating neurite outgrowth might induce neuronal reconstruction and help in the recovery of brain function. Working on this hypothesis, we recently observed that the chloroform extract of the Rosa damascena significantly induced the neurite outgrowth activity and inhibited the Aβ(25–35-induced atrophy and cell death. Further workup led the isolation of a very long polyunsaturated fatty acid having molecular formula C37H64O2 as an active constituent. The structure of this compound was established by extensive analysis of fragmentations observed in EI-MS mode. The isolated compound protected Aβ(25–35-induced atrophy and displayed strong neurite outgrowth activity. The length of dendrite in the cells treated with this compound were comparable to those of nerve growth factor (NGF treated cells.

  12. Protective Effects of Rosa damascena and Its Active Constituent on Aβ(25-35)-Induced Neuritic Atrophy.

    Science.gov (United States)

    Awale, Suresh; Tohda, Chihiro; Tezuka, Yasuhiro; Miyazaki, Makoto; Kadota, Shigetoshi

    2011-01-01

    Dementia is a clinical syndrome characterized by multiple cognitive deficits and causes progressive neurodegeneration leading eventually to death. The incidence of dementia is increasing worldwide with the increase in ageing population. However, no effective treatment is available yet. It has been hypothesized that drugs activating neurite outgrowth might induce neuronal reconstruction and help in the recovery of brain function. Working on this hypothesis, we recently observed that the chloroform extract of the Rosa damascena significantly induced the neurite outgrowth activity and inhibited the Aβ(25-35)-induced atrophy and cell death. Further workup led the isolation of a very long polyunsaturated fatty acid having molecular formula C(37)H(64)O(2) as an active constituent. The structure of this compound was established by extensive analysis of fragmentations observed in EI-MS mode. The isolated compound protected Aβ(25-35)-induced atrophy and displayed strong neurite outgrowth activity. The length of dendrite in the cells treated with this compound were comparable to those of nerve growth factor (NGF) treated cells.

  13. Insulin decreases atherosclerotic plaque burden and increases plaque stability via nitric oxide synthase in apolipoprotein E-null mice.

    Science.gov (United States)

    Mori, Yusaku; Chiang, Simon; Bendeck, Michelle P; Giacca, Adria

    2016-08-01

    It has been argued whether insulin accelerates or prevents atherosclerosis. Although results from in vitro studies have been conflicting, recent in vivo mice studies demonstrated antiatherogenic effects of insulin. Insulin is a known activator of endothelial nitric oxide synthase (NOS), leading to increased production of NO, which has potent antiatherogenic effects. We aimed to examine the role of NOS in the protective effects of insulin against atherosclerosis. Male apolipoprotein E-null mice (8 wk old) fed a high-cholesterol diet (1.25% cholesterol) were assigned to the following 12-wk treatments: control, insulin (0.05 U/day via subcutaneous pellet), N(ω)-nitro-l-arginine methyl ester hydrochloride (l-NAME, via drinking water at 100 mg/l), and insulin plus l-NAME. Insulin reduced atherosclerotic plaque burden in the descending aorta by 42% compared with control (plaque area/aorta lumen area: control, 16.5 ± 1.9%; insulin, 9.6 ± 1.3%, P < 0.05). Although insulin did not decrease plaque burden in the aortic sinus, macrophage accumulation in the plaque was decreased by insulin. Furthermore, insulin increased smooth muscle actin and collagen content and decreased plaque necrosis, consistent with increased plaque stability. In addition, insulin treatment increased plasma NO levels, decreased inducible NOS staining, and tended to increase phosphorylated vasodilator-stimulated phosphoprotein staining in the plaques of the aortic sinus. All these effects of insulin were abolished by coadministration of l-NAME, whereas l-NAME alone showed no effect. Insulin also tended to increase phosphorylated endothelial NOS and total neuronal NOS staining, effects not modified by l-NAME. In conclusion, we demonstrate that insulin treatment decreases atherosclerotic plaque burden and increases plaque stability through NOS-dependent mechanisms. Copyright © 2016 the American Physiological Society.

  14. Coseeded Schwann cells myelinate neurites from differentiated neural stem cells in neurotrophin-3-loaded PLGA carriers

    Science.gov (United States)

    Xiong, Yi; Zhu, Ji-Xiang; Fang, Zheng-Yu; Zeng, Cheng-Guang; Zhang, Chao; Qi, Guo-Long; Li, Man-Hui; Zhang, Wei; Quan, Da-Ping; Wan, Jun

    2012-01-01

    Biomaterials and neurotrophic factors represent promising guidance for neural repair. In this study, we combined poly-(lactic acid-co-glycolic acid) (PLGA) conduits and neurotrophin-3 (NT-3) to generate NT-3-loaded PLGA carriers in vitro. Bioactive NT-3 was released stably and constantly from PLGA conduits for up to 4 weeks. Neural stem cells (NSCs) and Schwann cells (SCs) were coseeded into an NT-releasing scaffold system and cultured for 14 days. Immunoreactivity against Map2 showed that most of the grafted cells (>80%) were differentiated toward neurons. Double-immunostaining for synaptogenesis and myelination revealed the formation of synaptic structures and myelin sheaths in the coculture, which was also observed under electron microscope. Furthermore, under depolarizing conditions, these synapses were excitable and capable of releasing synaptic vesicles labeled with FM1-43 or FM4-64. Taken together, coseeding NSCs and SCs into NT-3-loaded PLGA carriers increased the differentiation of NSCs into neurons, developed synaptic connections, exhibited synaptic activities, and myelination of neurites by the accompanying SCs. These results provide an experimental basis that supports transplantation of functional neural construction in spinal cord injury. PMID:22619535

  15. AMPK over-activation leads to accumulation of α-synuclein oligomers and decrease of neurites

    Science.gov (United States)

    Jiang, Peizhou; Gan, Ming; Ebrahim, Abdul Shukkur; Castanedes-Casey, Monica; Dickson, Dennis W.; Yen, Shu-Hui C.

    2012-01-01

    Neuronal inclusions of α-synuclein (α-syn), termed Lewy bodies, are a hallmark of Parkinson disease (PD). Increased α-syn levels can occur in brains of aging human and neurotoxin treated mice. Since previous studies have shown increased brain lactate levels in aging brains, in PD affected subjects when compared to age-matched controls, and in mice treated with MPTP, we tested the effects of lactate exposure on α-syn in a cell based-study. We demonstrated that (i) lactate treatment led to α-syn accumulation and oligomerization in a time- and concentration-dependent manner, (ii) such alterations were mediated via adenosine-monophosphate activated protein kinase (AMPK) and associated with increasing cytoplasmic phosphorylated AMPK levels, (iii) AMPK activation facilitated α-syn accumulation and phosphorylation, (iv) lactate treatment or overexpression of active form of AMPK decreased α-syn turnover and neurite outgrowth and (v) Lewy body-bearing neurons displayed abnormal cytoplasmic distribution of phosphorylated AMPK, which normally is located in nuclei. Together, our results suggest that chronic neuronal accumulation of α-syn induced by lactate-triggered AMPK activation in aging brains may be a novel mechanism underlying α-synucleionpathies in PD and related disorders. PMID:23200460

  16. Diffusion Tensor Imaging Tractography in Pure Neuritic Leprosy: First Experience Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Michele R. Colonna

    2016-01-01

    Full Text Available Five years after both right ulnar and median nerve decompression for paraesthesias and palsy, a patient, coming from Nigeria but living in Italy, came to our unit claiming to have persistent pain and combined median and ulnar palsy. Under suspicion of leprosy, skin and left sural nerve biopsy were performed. Skin tests were negative, but Schwann cells resulted as positive for acid-fast bacilli (AFB, leading to the diagnosis of Pure Neuritic Leprosy (PNL. The patient was given PB multidrug therapy and recovered from pain in two months. After nine months both High Resolution Ultrasonography (HRUS and Magnetic Resonance Imaging (MRI were performed, revealing thickening of the nerves. Since demyelination is common in PNL, the Authors started to use Diffusion Tensor Imaging Tractography (DTIT to get better morphological and functional data about myelination than does the traditional imaging. DTIT proved successful in showing myelin discontinuity, reorganization, and myelination, and the Authors suggest that it can give more information about the evolution of the disease, as well as further indications for surgery (nerve decompression, nerve transfers, and babysitting for distal effector protection, and should be added to traditional imaging tools in leprosy.

  17. Community-based statins and advanced carotid plaque: Role of CD163 positive macrophages in lipoprotein-associated phospholipase A2 activity in atherosclerotic plaque.

    Science.gov (United States)

    Otsuka, Fumiyuki; Zhao, XiaoQing; Trout, Hugh H; Qiao, Ye; Wasserman, Bruce A; Nakano, Masataka; Macphee, Colin H; Brandt, Martin; Krug-Gourley, Sue; Guo, Liang; Ladich, Elena R; Cheng, Qi; Davis, Harry R; Finn, Aloke V; Virmani, Renu; Kolodgie, Frank D

    2017-12-01

    Lipoprotein-associated phospholipase A2 (Lp-PLA2), an enzymatic inflammatory biomarker primarily bound to low-density lipoprotein cholesterol, is associated with an approximate twofold increased risk of cardiovascular disease and stroke. Despite indications that circulating Lp-PLA2 is sensitive to statins, it remains largely unknown whether statin usage exerts local effects on Lp-PLA2 expression at the site of atheromatous plaque. Carotid plaques (n = 38) were prospectively collected from symptomatic (n = 18) and asymptomatic (n = 20) patients with (n = 20) or without (n = 18) documented statin history. In all cases, endarterectomy was performed where the primary stenosis was removed in an undisturbed manner. Serial cryosections of the presenting lesion were assessed histologically for macrophages, Lp-PLA2, and cell death (apoptotic index). Symptomatic lesions exhibited less calcification, with greater inflammation characterized by increased expression of CD68+ and CD163+ macrophage subsets, and Lp-PLA2. Symptomatic plaques also exhibited greater necrotic core area and increased apoptosis, as compared with asymptomatic lesions. In contrast, statin treatment did not appear to influence any of these parameters, except for the extent of apoptosis, which was less in statin treated as compared with statin naïve lesions. Overall, Lp-PLA2 expression correlated positively with necrotic core area, CD68+ and CD163+ macrophage area, and cell death. Finally, in vitro assays and dual immunofluorescence staining confirmed CD163-expressing monocytes/macrophages are also a major source of Lp-PLA2. Statin treatment has no effect on local atherosclerotic lesion Lp-PLA2 activity, therefore, the addition of anti-inflammatory treatments to further decrease macrophage Lp-PLA2 expression in atherosclerotic lesions may reduce lesional inflammation and cell death, and prevent necrotic core expansion and lesion progression. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Assessment of dental plaque by optoelectronic methods

    Science.gov (United States)

    Negrutiu, Meda-Lavinia; Sinescu, Cosmin; Bortun, Cristina Maria; Levai, Mihaela-Codrina; Topala, Florin Ionel; Crǎciunescu, Emanuela Lidia; Cojocariu, Andreea Codruta; Duma, Virgil Florin; Podoleanu, Adrian Gh.

    2016-03-01

    The formation of dental biofilm follows specific mechanisms of initial colonization on the surface, microcolony formation, development of organized three dimensional community structures, and detachment from the surface. The structure of the plaque biofilm might restrict the penetration of antimicrobial agents, while bacteria on a surface grow slowly and display a novel phenotype; the consequence of the latter is a reduced sensitivity to inhibitors. The aim of this study was to evaluate with different optoelectronic methods the morphological characteristics of the dental biofilm. The study was performed on samples from 25 patients aged between 18 and 35 years. The methods used in this study were Spectral Domain Optical Coherence Tomography (SD-OCT) working at 870 nm for in vivo evaluations and Scanning Electron Microscopy (SEM) for validations. For each patient a sample of dental biofilm was obtained directly from the vestibular surface of the teeth's. SD-OCT produced C- and B-scans that were used to generate three dimensional (3D) reconstructions of the sample. The results were compared with SEM evaluations. The biofilm network was dramatically destroyed after the professional dental cleaning. OCT noninvasive methods can act as a valuable tool for the 3D characterization of dental biofilms.

  19. Plaques and tangles as well as Lewy-type alpha synucleinopathy are associated with formed visual hallucinations.

    Science.gov (United States)

    Jacobson, Sandra A; Morshed, Trisha; Dugger, Brittany N; Beach, Thomas G; Hentz, Joseph G; Adler, Charles H; Shill, Holly A; Sabbagh, Marwan N; Belden, Christine M; Sue, Lucia I; Caviness, John N; Hu, Chengcheng

    2014-09-01

    Previous research has linked complex or formed visual hallucinations (VH) to Lewy-type alpha-synucleinopathy (LTS) in neocortical and limbic areas. As Alzheimer's disease pathology often co-occurs with LTS, we questioned whether this pathology - amyloid plaques and neurofibrillary tangles - might also be linked to VH. We performed a semi-quantitative neuropathological study across brainstem, limbic, and cortical structures in subjects with a documented clinical history of VH and a clinicopathological diagnosis of Parkinson's disease (PD), Alzheimer's disease (AD), or dementia with Lewy bodies (DLB). 173 subjects - including 50 with VH and 123 without VH - were selected from the Arizona Study of Aging and Neurodegenerative Disorders. Clinical variables examined included the Mini-mental State Exam, Hoehn & Yahr stage, and total dopaminergic medication dose. Neuropathological variables examined included total and regional LTS and plaque and tangle densities. A significant relationship was found between the density of LTS and the presence of VH in PD, AD, and DLB. Plaque and tangle densities also were associated with VH in PD (p = .003 for plaque and p = .004 for tangles) but not in AD, where densities were high regardless of the presence of hallucinations. Furthermore, with DLB cases excluded, comorbidity of PD and AD was significantly more prevalent among subjects + VH than subjects -VH (p < .001). These findings suggest that both AD and PD neuropathology contribute to the pathogenesis of VH. Incident VH could be predictive of concomitant AD/PD pathology even when criteria are not met for a second diagnosis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Vulnerable plaque detection: The role of 18-fluorine ...

    African Journals Online (AJOL)

    Shazreen Shaharuddin

    2013-07-22

    Jul 22, 2013 ... fluorodeoxyglucose in identifying high risk patients. Shazreen ... total occlusion.2 Histologically, cross sectional atheromatous pla- que reveals .... Family history .... Plaque characterization is tabulated in Table 3. Majority of.

  1. In silico analyses of metagenomes from human atherosclerotic plaque samples

    DEFF Research Database (Denmark)

    Mitra, Suparna; Drautz-Moses, Daniela I; Alhede, Morten

    2015-01-01

    a challenge. RESULTS: To investigate microbiome diversity within human atherosclerotic tissue samples, we employed high-throughput metagenomic analysis on: (1) atherosclerotic plaques obtained from a group of patients who underwent endarterectomy due to recent transient cerebral ischemia or stroke. (2......) Presumed stabile atherosclerotic plaques obtained from autopsy from a control group of patients who all died from causes not related to cardiovascular disease. Our data provides evidence that suggest a wide range of microbial agents in atherosclerotic plaques, and an intriguing new observation that shows...... these microbiota displayed differences between symptomatic and asymptomatic plaques as judged from the taxonomic profiles in these two groups of patients. Additionally, functional annotations reveal significant differences in basic metabolic and disease pathway signatures between these groups. CONCLUSIONS: We...

  2. SPECT Imaging Agents for Detecting Cerebral β-Amyloid Plaques

    Directory of Open Access Journals (Sweden)

    Masahiro Ono

    2011-01-01

    Full Text Available The development of radiotracers for use in vivo to image β-amyloid (Aβ plaques in cases of Alzheimer's disease (AD is an important, active area of research. The presence of Aβ aggregates in the brain is generally accepted as a hallmark of AD. Since the only definitive diagnosis of AD is by postmortem staining of affected brain tissue, the development of techniques which enable one to image Aβ plaques in vivo has been strongly desired. Furthermore, the quantitative evaluation of Aβ plaques in the brain could facilitate evaluation of the efficacy of antiamyloid therapies currently under development. This paper reviews the current situation in the development of agents for SPECT-based imaging of Aβ plaques in Alzheimer's brains.

  3. Correlation between aortic/carotid atherosclerotic plaques and cerebral infarction.

    Science.gov (United States)

    Wang, Baojun; Sun, Shaoli; Liu, Guorong; Li, Yuechun; Pang, Jiangxia; Zhang, Jingfen; Yang, Lijuan; Li, Ruiming; Zhang, Hui; Jiang, Changchun; Li, Xiue

    2013-08-01

    The aim of this study was to investigate the correlation between aortic/carotid atherosclerotic plaques and cerebral infarction. We examined 116 cases of cerebral infarction using transcranial Doppler ultrasound in order to exclude cerebrovascular stenosis. Transesophageal echocardiography and color Doppler ultrasound were used to detect aortic atherosclerotic plaques (AAPs) and carotid atherosclerotic plaques (CAPs). AAPs were detected in a total of 70 of the 116 cases (60.3%), including 56 with moderate/severe atherosclerotic changes (48.3%). The difference in the incidence of various types of infarction between APP severity levels was significant (PCAPs (55.2%), including 46 with unstable plaque (39.7%). The difference in the incidence of various types of infarction between CAP stability levels was significant (PCAP are significant causes of embolic infarction without stenosis in the internal carotid arteries.

  4. Pleural plaques and cigarette smoking in asbestos workers.

    Science.gov (United States)

    Weiss, W; Levin, R; Goodman, L

    1981-06-01

    In a survey of 45 men aged 40 or over who had worked five years or more in an asbestos manufacturing plant, the prevalence of pleural plaques was studied with respect to age, duration of asbestos exposure, estimated cumulative asbestos dose, and smoking habit. Plaques were found in 38 to 53% of the men, depending on the interpretation of the chest film reader. Cigarette habit appeared to be the most important factor; the prevalence was lowest in non-smokers, intermediate in current smokers, and particularly high in exsmokers. There was some confounding of this relationship by estimated cumulative asbestos dose but such confounding did not seem to be sufficient to explain fully the relationship between the prevalence of plaques and smoking habit. Both factors must be considered in studies of the risk of pleural plaques in asbestos workers.

  5. Argonne National Laboratory research offers clues to Alzheimer's plaques

    CERN Multimedia

    2003-01-01

    Researchers from Argonne National Laboratory and the University of Chicago have developed methods to directly observe the structure and growth of microscopic filaments that form the characteristic plaques found in the brains of those with Alzheimer's Disease (1 page).

  6. Evidence for xylitol 5-P production in human dental plaque

    Energy Technology Data Exchange (ETDEWEB)

    Waaler, S.M. (Department of Preclinical Techniques and Material Sciences and Department of Pedodontics, Dental Faculty, University of Oslo, Oslo (Norway))

    1992-01-01

    The Turku sugar studies indicated that xylitol may possess a caries-therapeutic effect. More recent data show that xylotol exhibits a bacteriostatic activity on a wide range of bacteria based on uptake and expulsion of xylitol. Intracellular xylitol 5-P appears to be a key substance associated with inhibition of bacterial metabolism by xylitol. This has been shown in studies with pure strains of bacteria, mainly Streptococcus mutans. The aim of the present study was to examine if production of xylitol 5-P occurs in freshly collected dental plaque which is exposed to labeled xylitol. Plaque extracts were analyzed by thin-layer chromatography combined with autoradiography and high performance liquid chromatography. Strong indications were obtained that xylitol 5-P is readily produced by dental plaque. No other significant xylitol metabolites were identified. The bacteriostatic properties of xylitol in plaque are a mechanism which may well account for the caries-therapeutic effect of xylitol. (au).

  7. Comparative professional plaque removal study using 8 branded toothbrushes.

    Science.gov (United States)

    Claydon, N; Addy, M; Scratcher, C; Ley, F; Newcombe, R

    2002-04-01

    Considerable interest has been shown in the plaque removal properties of modern toothbrush designs. The primary aim of the study was to compare the plaque removal properties of 8 relatively recent designs of manual toothbrush using a professional tooth brusher and within a commonly used time frame. A secondary aim was established to utilise the data to observationally appraise plaque accumulation together with the patterns of removal as a consequence of using the timed professional tooth brusher. The method was an 8-period, single-examiner, randomized, blind cross-over study involving 24 healthy volunteers, balanced for residual effects. Subjects accumulated plaque over a 4 day no oral hygiene period. On day 4, the accumulated plaque was scored by plaque index at the mesial, mid and distal sites of each of the buccal and lingual surfaces of the assessed teeth. Subjects were then removed from the assessment area where they received a professional brushing timed to last 48 s. Brushing was completed according to pre-study training without toothpaste and was followed by a re-scoring of the remaining plaque. A washout period of 3 days was then allowed prior to the next period during which normal oral hygiene was resumed. Similar quantities of plaque accumulated in each arch, although the difference between the buccal and lingual surfaces was of the order of 30%. The professional toothbrusher removed approximately 40% of the accumulated plaque in the 48 s allocated. The buccal surfaces were most effectively cleaned (approximately 45%) compared with the lingual (approximately 25%), with the plaque removal in the mesial and mid sections approaching 40% and 60% respectively. The difference in performance between the test brushes corresponded to 5% of the residual plaque values with none being significantly more efficient overall. Pair wise site comparisons did produce differences of the order of 10% (p=0.004) at the mesio-buccal, and 8% (p=0.030) at the mid-buccal sites

  8. High shear stress relates to intraplaque haemorrhage in asymptomatic carotid plaques

    DEFF Research Database (Denmark)

    Tuenter, A.; Selwaness, M.; Arias Lorza, A.

    2016-01-01

    BACKGROUND AND AIMS: Carotid artery plaques with vulnerable plaque components are related to a higher risk of cerebrovascular accidents. It is unknown which factors drive vulnerable plaque development. Shear stress, the frictional force of blood at the vessel wall, is known to influence plaque...

  9. Lipid-Rich Plaque Masquerading as a Coronary Thrombus

    OpenAIRE

    Rezkalla, Shereif H.; Holmes, David R.

    2006-01-01

    A 43-year-old woman presented with exertional chest pressure. Right coronary angiography showed a clear filling defect. Intravascular ultrasound revealed a plaque with 80% stenosis and a large lipid pool. Therefore, a stent was placed, and the patient became angina-free. Lipid-rich plaques are a cause of angiographic filling defects. Intravascular ultrasound is an integral part of coronary artery evaluation.

  10. Imaging Modalities to Identity Inflammation in an Atherosclerotic Plaque

    OpenAIRE

    Goel, Sunny; Miller, Avraham; Agarwal, Chirag; Zakin, Elina; Acholonu, Michael; Gidwani, Umesh; Sharma, Abhishek; Kulbak, Guy; Shani, Jacob; Chen, On

    2015-01-01

    Atherosclerosis is a chronic, progressive, multifocal arterial wall disease caused by local and systemic inflammation responsible for major cardiovascular complications such as myocardial infarction and stroke. With the recent understanding that vulnerable plaque erosion and rupture, with subsequent thrombosis, rather than luminal stenosis, is the underlying cause of acute ischemic events, there has been a shift of focus to understand the mechanisms that make an atherosclerotic plaque unstabl...

  11. Carotid plaque burden as a measure of subclinical atherosclerosis

    DEFF Research Database (Denmark)

    Sillesen, Henrik; Muntendam, Pieter; Adourian, Aram

    2012-01-01

    The purpose of this study was to compare carotid plaque burden, carotid intima-media thickness (cIMT), ankle-brachial index (ABI), and abdominal aortic diameter (AAD) to coronary artery calcium score (CACS) in people without known cardiovascular disease.......The purpose of this study was to compare carotid plaque burden, carotid intima-media thickness (cIMT), ankle-brachial index (ABI), and abdominal aortic diameter (AAD) to coronary artery calcium score (CACS) in people without known cardiovascular disease....

  12. Complement factor C5a induces atherosclerotic plaque disruptions.

    Science.gov (United States)

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

    2014-10-01

    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. © 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  13. The effect of chewing gum on dental plaque accumulation

    OpenAIRE

    Karami Nogourani M.; Banihashemi M

    2010-01-01

    "nBackground and Aims: Studies show that sucrose containing chewing gums are cariogenic. The aim of this study was to evaluate the effect of two commercial chewing gums with and without sucrose on dental plaque accumulation compared with the control group. "nMaterials and Methods: In this clinical study, plaque accumulation during three 7-day periods (with two weeks interval) was recorded (Sillness & Loe Index) in a group of 23 volunteer male dental students who chewed in th...

  14. Nonspecific Factors in Monkey Tissues and Serum Causing Inhibition of Plaque Formation and Hemagglutination by Dengue Viruses

    Science.gov (United States)

    Nash, Donald R.; Halstead, Scott B.; Stenhouse, Andrew C.; McCue, Carolyn

    1971-01-01

    Normal monkey serum and the supernatant fluid from different triturated monkey tissues have been studied for the presence of nonspecific arbovirus hemagglutination and plaque forming inhibitors of dengue viruses types 1, 2, 3, and 4. Hemagglutination inhibition (HI) activity was present in most tissue specimens and demonstrated a significant gradient of effectiveness starting with, respectively, serum, spleen, adrenal, and lung having a high degree of activity, whereas skin, heart, muscle, brain, and liver demonstrated low HI titers. A slightly reversed gradient of effectiveness was obtained for the case of dengue virus inhibition of plaque formation with bile, liver, thymus, spleen, and adrenal giving high 50% plaque reduction titers and heart, muscle, serum, skin, and fat demonstrating little or no activity. Analysis by Sephadex G-200 chromatography and sucrose density gradient centrifugation suggests that HI and plaque formation inhibition are independent activities of normal serum or tissue constituents or both. Also, in addition to the physical methods of characterization, chemical treatment by absorption with kaolin or acetone extraction indicate both phenomena to be the result of the action of lipids or lipoproteins. PMID:16557953

  15. Effect of Quercus infectoria and Rosa damascena on lipid profile and atherosclerotic plaque formation in rabbit model of hyperlipidemia.

    Science.gov (United States)

    Gholamhoseinian, A; Shahouzehi, B; Joukar, S; Iranpoor, M

    2012-01-01

    Hyperlipidemia is the cause of many complications in the human societies. In this study, the effect of methanol extracts of Quercus infectoria (QI) galls and Rosa damascena (RD) Mill flower were studied on lipid profile and atherosclerotic plaques formation in hyperlipidemic rabbits. Thirty-six New Zeland white rabbits randomly divided into 6 groups as control (I), hyperlipidemic (II), hyperlipidemic+QI (III), hyperlipidemic+RD (IV), +Atorvastolin (V) and hyperlipidemic+Orlistat (VI) and were fed with high fat diet (0.5% cholesterol and 16% hydrogenated vegetable oil) for 45 days. At the end of the study period, lipid profile and plaque formation were assessed. Total Cholesterol (TC), Low Density Lipoprotein (LDL) and Triglyceride (TG) levels were significantly increased in hyperlipidemic group compared with control group (p < 0.001). Methanol extract consumption of Quercus infectoria significantly decreased plasma levels of TC, TG and LDL (p < 0.001). It also decreased plaques formation in semi lunar valve and thoracic aorta. Rosa damascena mill flower methanol extract moderately decreased the levels of TC, TG, LDL and plaques formation but it was not significant. HDL levels and weight of animals did not show significant difference among groups. Based on the doses used in this study, our finding indicated that QI but no RD methanol extract has anti atherogenic and hypolipidemic activities.

  16. Supragingival Plaque Microbial Community Analysis of Children with Halitosis.

    Science.gov (United States)

    Ren, Wen; Zhang, Qun; Liu, Xuenan; Zheng, Shuguo; Ma, Lili; Chen, Feng; Xu, Tao; Xu, Baohua

    2016-12-28

    As one of the most complex human-associated microbial habitats, the oral cavity harbors hundreds of bacteria. Halitosis is a prevalent oral condition that is typically caused by bacteria. The aim of this study was to analyze the microbial communities and predict functional profiles in supragingival plaque from healthy individuals and those with halitosis. Ten preschool children were enrolled in this study; five with halitosis and five without. Supragingival plaque was isolated from each participant and 16S rRNA gene pyrosequencing was used to identify the microbes present. Samples were primarily composed of Actinobacteria, Bacteroidetes, Proteobacteria, Firmicutes, Fusobacteria, and Candidate phylum TM7. The α and β diversity indices did not differ between healthy and halitosis subjects. Fifteen operational taxonomic units (OTUs) were identified with significantly different relative abundances between healthy and halitosis plaques, and included the phylotypes of Prevotella sp., Leptotrichia sp., Actinomyces sp., Porphyromonas sp., Selenomonas sp., Selenomonas noxia, and Capnocytophaga ochracea. We suggest that these OTUs are candidate halitosis-associated pathogens. Functional profiles were predicted using PICRUSt, and nine level-3 KEGG Orthology groups were significantly different. Hub modules of co-occurrence networks implied that microbes in halitosis dental plaque were more highly conserved than microbes of healthy individuals' plaque. Collectively, our data provide a background for the oral microbiota associated with halitosis from supragingival plaque, and help explain the etiology of halitosis.

  17. Imaging the event-prone coronary artery plaque.

    Science.gov (United States)

    Giannopoulos, Andreas A; Benz, Dominik C; Gräni, Christoph; Buechel, Ronny R

    2017-07-06

    Acute coronary events, the dreaded manifestation of coronary atherosclerosis, remain one of the main contributors to mortality and disability in the developed world. The majority of those events are associated with atherosclerotic plaques-related thrombus formation following an acute disruption, that being rupture or erosion, of an event-prone lesion. These historically termed vulnerable plaques have been the target of numerous benchtop and clinical research endeavors, yet to date without solid results that would allow for early identification and potential treatment. Technological leaps in cardiovascular imaging have provided novel insights into the formation and role of the event-prone plaques. From intracoronary optical coherence tomography that has enhanced our understanding of the pathophysiological mechanisms of plaque disruption, over coronary computed tomography angiography that enables non-invasive serial plaque imaging, and positron emission tomography poised to be rapidly implemented into clinical practice to the budding field of plaque imaging with cardiac magnetic resonance, we summarize the invasive and non-invasive imaging modalities currently available in our armamentarium. Finally, the current status and potential future imaging directions are critically appraised.

  18. Brain Tissue Compartment Density Estimated Using Diffusion-Weighted MRI Yields Tissue Parameters Consistent With Histology

    Science.gov (United States)

    Sepehrband, Farshid; Clark, Kristi A.; Ullmann, Jeremy F.P.; Kurniawan, Nyoman D.; Leanage, Gayeshika; Reutens, David C.; Yang, Zhengyi

    2015-01-01

    We examined whether quantitative density measures of cerebral tissue consistent with histology can be obtained from diffusion magnetic resonance imaging (MRI). By incorporating prior knowledge of myelin and cell membrane densities, absolute tissue density values were estimated from relative intra-cellular and intra-neurite density values obtained from diffusion MRI. The NODDI (neurite orientation distribution and density imaging) technique, which can be applied clinically, was used. Myelin density estimates were compared with the results of electron and light microscopy in ex vivo mouse brain and with published density estimates in a healthy human brain. In ex vivo mouse brain, estimated myelin densities in different sub-regions of the mouse corpus callosum were almost identical to values obtained from electron microscopy (Diffusion MRI: 42±6%, 36±4% and 43±5%; electron microscopy: 41±10%, 36±8% and 44±12% in genu, body and splenium, respectively). In the human brain, good agreement was observed between estimated fiber density measurements and previously reported values based on electron microscopy. Estimated density values were unaffected by crossing fibers. PMID:26096639

  19. Chlorhexidine mouthwash plaque levels and gingival health.

    Science.gov (United States)

    Richards, Derek

    2017-06-23

    Data sourcesCochrane Oral Health's Trials Register; Cochrane Central Register of Controlled Trials (CENTRAL) Medline; clinicaltrials.gov and the World Health Organization International Clinical Trials Registry Platform. There were no language or date restrictions on searches.Study selectionRandomised controlled trials (RCTs) assessing the effects of chlorhexidine mouthrinse used as an adjunct to mechanical oral hygiene procedures for at least four weeks on gingivitis in children and adults.Data extraction and synthesisTwo reviewers independently abstracted data and assessed risk of bias. Mean and standardised mean differences were used for continuous outcomes and risk ratios for dichotomous outcomes. Meta-analysis was carried out where studies of similar comparisons reported the same outcomes at the same time interval.ResultsFifty-one RCTs involving a total of 5,345 patients were included. Only one study was at low risk of bias, the other 50 were at high risk. For patients with mild gingivitis (gingival index [GI] 0 to 3 scale) four to six weeks' use of chlorhexidine mouthrinse reduced gingivitis by 0.21 (95% CI; 0.11 to 0.31) with a similar effect at six months. There were insufficient data to assess the effect on patients with moderate or severe gingival inflammation. For plaque there was a larger effect in favour of chlorhexidine mouthrinse at four to six weeks, SMD (standardised mean difference) = -1.45 (95% CI; -1.90 to -1.00), with a similarly large reduction at six months. A large increase in extrinsic tooth staining was seen with chlorhexidine use at four to six weeks, SMD = 1.07 (95%CI; 0.80 to 1.34) and seven to twelve weeks and six months. A range of other adverse effects were reported including taste disturbance/alteration, oral mucosa symptoms including soreness, irritation, mild desquamation and mucosal ulceration/erosions, and a general burning sensation or a burning tongue or both.ConclusionsThere is high quality evidence from studies that reported

  20. The effect of pH, temperature and plaque thickness on the hydrolysis of monofluorophosphate in experimental dental plaque.

    Science.gov (United States)

    Pearce, E I F; Dibdin, G H

    2003-01-01

    Monofluorophosphate (MFP), an anti-caries agent commonly used in toothpaste, is known to be degraded to fluoride and orthophosphate by bacterial phosphatases in dental plaque. We have examined the effect of pH, temperature, plaque thickness and some ions on this process. Both natural plaque and artificial microcosm plaque incubated with purified MFP at pH 4-10 showed an optimum pH of approximately 8 for hydrolysis. Diffusion and concomitant hydrolysis were examined in an apparatus in which artificial plaque was held between rigid membranes separating two chambers. When MFP diffused through a plaque of 0.51-mm thickness over 4 h it was almost completely hydrolysed at pH 8, but hydrolysis on diffusion decreased as the pH deviated from 8. MFP in toothpaste extract showed a similar pH susceptibility to hydrolysis, according to the inherent pH of the toothpaste. Hydrolysis of MFP in the toothpaste was reduced by no more than 10% when compared with a matched-pH control, suggesting that other toothpaste ingredients had no major influence on hydrolysis. Transport was slower and hydrolysis at pH 6 more complete the thicker the plaque, but hydrolysis was not significantly slower at 23 degrees C than at 37 degrees C. The addition of various potential activating or inhibiting ions at 0.1 and 1.0 mmol/l had small and non-significant effects on hydrolysis. The results suggest that MFP toothpaste should be formulated and used to maximise enzymic hydrolysis of this complex anion, and that plaque pH control is probably the most important factor. Copyright 2003 S. Karger AG, Basel

  1. Synaptic profiles during neurite extension, refinement and retraction in the developing cochlea

    Directory of Open Access Journals (Sweden)

    Huang Lin-Chien

    2012-12-01

    Full Text Available Abstract Background During development, excess synapses form between the central and peripheral nervous systems that are then eliminated to achieve correct connectivity. In the peripheral auditory system, the developing type I spiral ganglion afferent fibres undergo a dramatic re-organisation, initially forming connections with both sensory inner hair cells (IHCs and outer hair cells (OHCs. The OHC connections are then selectively eliminated, leaving sparse innervation by type II afferent fibres, whilst the type I afferent synapses with IHCs are consolidated. Results We examined the molecular makeup of the synaptic contacts formed onto the IHCs and OHCs during this period of afferent fibre remodelling. We observed that presynaptic ribbons initially form at all the afferent neurite contacts, i.e. not only at the expected developing IHC-type I fibre synapses but also at OHCs where type I fibres temporarily contact. Moreover, the transient contacts forming onto OHCs possess a broad set of pre- and postsynaptic proteins, suggesting that functional synaptic connections are formed prior to the removal of type I fibre innervation. AMPA-type glutamate receptor subunits were transiently observed at the base of the OHCs, with their downregulation occurring in parallel with the withdrawal of type I fibres, dispersal of presynaptic ribbons, and downregulation of the anchoring proteins Bassoon and Shank. Conversely, at developing type I afferent IHC synapses, the presence of pre- and postsynaptic scaffold proteins was maintained, with differential plasticity in AMPA receptor subunits observed and AMPA receptor subunit composition changing around hearing onset. Conclusions Overall our data show a differential balance in the patterns of synaptic proteins at developing afferent IHC versus OHC synapses that likely reflect their stable versus transient fates.

  2. Macrophage-targeted photodynamic detection of vulnerable atherosclerotic plaque

    Science.gov (United States)

    Hamblin, Michael R.; Tawakol, Ahmed; Castano, Ana P.; Gad, Faten; Zahra, Touqir; Ahmadi, Atosa; Stern, Jeremy; Ortel, Bernhard; Chirico, Stephanie; Shirazi, Azadeh; Syed, Sakeena; Muller, James E.

    2003-06-01

    Rupture of a vulnerable atherosclerotic plaque (VP) leading to coronary thrombosis is the chief cause of sudden cardiac death. VPs are angiographically insignificant lesions, which are excessively inflamed and characterized by dense macrophage infiltration, large necrotic lipid cores, thin fibrous caps, and paucity of smooth muscle cells. We have recently shown that chlorin(e6) conjugated with maleylated albumin can target macrophages with high selectivity via the scavenger receptor. We report the potential of this macrophage-targeted fluorescent probe to localize in VPs in a rabbit model of atherosclerosis, and allow detection and/or diagnosis by fluorescence spectroscopy or imaging. Atherosclerotic lesions were induced in New Zealand White rabbit aortas by balloon injury followed by administration of a high-fat diet. 24-hours after IV injection of the conjugate into atherosclerotic or normal rabbits, the animals were sacrificed, and aortas were removed, dissected and examined for fluorescence localization in plaques by fiber-based spectrofluorimetry and confocal microscopy. Dye uptake within the aortas was also quantified by fluorescence extraction of samples from aorta segments. Biodistribution of the dye was studied in many organs of the rabbits. Surface spectrofluorimetry after conjugate injection was able to distinguish between plaque and adjacent aorta, between atherosclerotic and normal aorta, and balloon-injured and normal iliac arteries with high significance. Discrete areas of high fluorescence (up to 20 times control were detected in the balloon-injured segments, presumably corresponding to macrophage-rich plaques. Confocal microscopy showed red ce6 fluorescence localized in plaques that showed abundant foam cells and macrophages by histology. Extraction data on aortic tissue corroborated the selectivity of the conjugate for plaques. These data support the strategy of employing macrophage-targeted fluorescent dyes to detect VP by intravascular

  3. Eosinophil Cationic Protein, Carotid Plaque, and Incidence of Stroke.

    Science.gov (United States)

    Sundström, Johannes; Söderholm, Martin; Borné, Yan; Nilsson, Jan; Persson, Margaretha; Östling, Gerd; Melander, Olle; Orho-Melander, Marju; Engström, Gunnar

    2017-10-01

    ECP (eosinophil cationic protein) is a marker of eosinophil activity and degranulation, which has been linked to atherosclerosis and cardiovascular disease. We examined the relationship between ECP, carotid plaque, and incidence of stroke in a prospective population-based cohort. The subjects participated in the Malmö Diet and Cancer Study between 1991 and 1994. A total of 4706 subjects with no history of stroke were included (40% men; mean age, 57.5 years). Carotid plaque was determined by B-mode ultrasound of the right carotid artery. Incidence of stroke was followed up during a mean period of 16.5 years in relation to plasma ECP levels. Subjects in the third tertile (versus first tertile) of ECP tended to have higher prevalence of carotid plaque (odds ratio: 1.18; 95% confidence interval: 1.003-1.39; P =0.044 after multivariate adjustments). A total of 258 subjects were diagnosed with ischemic stroke (IS) during follow-up. ECP was associated with increased incidence of IS after risk factor adjustment (hazard ratio, 1.57; 95% confidence interval: 1.13-2.18; for third versus first tertile; P =0.007). High ECP was associated with increased risk of IS in subjects with carotid plaque. The risk factor-adjusted hazard ratio for IS was 1.86 (95% confidence interval: 1.32-2.63) in subjects with carotid plaque and ECP in the top tertile, compared with those without plaque and ECP in the first or second tertiles. High ECP is associated with increased incidence of IS. The association between ECP and IS was also present in the subgroup with carotid plaque. © 2017 American Heart Association, Inc.

  4. Acid production in dental plaque after exposure to probiotic bacteria

    Directory of Open Access Journals (Sweden)

    Keller Mette K

    2012-10-01

    Full Text Available Abstract Background The increasing interest in probiotic lactobacilli in health maintenance has raised the question of potential risks. One possible side effect could be an increased acidogenicity in dental plaque. The aim of this study was to investigate the effect of probiotic lactobacilli on plaque lactic acid (LA production in vitro and in vivo. Methods In the first part (A, suspensions of two lactobacilli strains (L. reuteri DSM 17938, L. plantarum 299v were added to suspensions of supragingival dental plaque collected from healthy young adults (n=25. LA production after fermentation with either xylitol or fructose was analyzed. In the second part (B, subjects (n=18 were given lozenges with probiotic lactobacilli (L. reuteri DSM 17938 and ATCC PTA 5289 or placebo for two weeks in a double-blinded, randomized cross-over trial. The concentration of LA in supragingival plaque samples was determined at baseline and after 2 weeks. Salivary counts of mutans streptococci (MS and lactobacilli were estimated with chair-side methods. Results Plaque suspensions with L. reuteri DSM 17938 produced significantly less LA compared with L. plantarum 299v or controls (p Conclusion Lactic acid production in suspensions of plaque and probiotic lactobacilli was strain-dependant and the present study provides no evidence of an increase in plaque acidity by the supply of selected probiotic lactobacilli when challenged by fructose or xylitol. The study protocol was approved by The Danish National Committee on Biomedical Research Ethics (protocol no H-2-2010-112. Trial registration NCT01700712

  5. Effect of essential oil mouthwashes on plaque and gingivitis.

    Science.gov (United States)

    Richards, Derek

    2017-06-23

    Data sourcesMedline, Embase, LILACS and Scopus database.Study selectionStudies were screened independently by three reviewers. Randomised controlled trials with a minimum of six months follow-up of daily use of essential oils-containing (EO) mouthwashes compared with placebo, flossing or cetylpyridinium chloride (CPC) as adjuncts to mechanical plaque control were considered.Data extraction and synthesisData were abstracted by two reviewers and study quality assessed using the Cochrane risk of bias tool. Dental plaque was summarised using the Turesky modification of the Quigley-Hein Index (QHI), gingivitis using three indices; the Gingival Index (GI) by Loe and Silness, the Modified Gingival Index (MGI) and bleeding upon probing. Mean and standard deviations were reported and meta-analysis conducted. Sources of effect modification were investigated using meta-regression.ResultsSixteen trials were included involving 4016 patients in total. Study quality was considered to be moderate to low. Compared with placebo meta-analysis of 14 studies showed statistically significant differences in favour of EO mouthwashes for plaque and gingival indices. Meta-analysis of four studies also demonstrated statistically lower levels of plaque and gingivitis for EO mouthwashes compared with cetylpyridium chloride (CPC). Meta-regression indicated that heterogeneity observed in plaque scores was mainly explained by the percentage of males in a trial and supervision of the mouthwash use.ConclusionsIn patients with gingivitis, EO-containing mouthwashes are more efficacious for the reduction of plaque and gingival inflammation than mechanical plaque control either alone (placebo) or in combination with mouthwashes with CPC. The expected benefits may be clinically relevant and may be also observed in the interproximal area.

  6. Monocyte Adhesion and Plaque Recruitment During Atherosclerosis Development Is Regulated by the Adapter Protein Chat-H/SHEP1.

    Science.gov (United States)

    Herbin, Olivier; Regelmann, Adam G; Ramkhelawon, Bhama; Weinstein, Erica G; Moore, Kathryn J; Alexandropoulos, Konstantina

    2016-09-01

    The chronic inflammation associated with atherosclerosis is caused by lipid deposition followed by leukocyte recruitment to the arterial wall. We previously showed that the hematopoietic cell-specific adaptor protein Cas- and Hef1-associated signal transducer hematopoietic isoform (Chat-H)/SHEP1 regulated lymphocyte adhesion and migration. In this study, we analyzed the role of Chat-H in atherosclerosis development. Using Chat-H-deficient bone marrow transplantation in low-density lipoprotein receptor-deficient mice, we found that Chat-H regulated atherosclerotic plaque formation. Chat-H deficiency in hematopoietic cells associated with lower plaque complexity and fewer leukocytes in the lesions, whereas myeloid-specific deletion of Chat-H was sufficient for conferring atheroprotection. Chat-H deficiency resulted in reduced recruitment of classical Ly6c(high) and nonclassical Ly6c(low) monocytes to the plaques, which was accompanied by increased numbers of both monocyte subsets in the blood. This associated with defective adhesion of Chat-H-deficient Ly6c(high) and Ly6c(low) monocytes to vascular cell adhesion molecule-1 in vitro and impaired infiltration of fluorescent bead-loaded monocytes to atherosclerotic plaques. In contrast, Chat-H was dispensable for CX3CL1 and CCR1/CCR5-dependent migration of monocytes. Our findings highlight Chat-H as a key protein that regulates atherosclerosis development by controlling monocyte adhesion and recruitment to the plaques and identify a novel target that may be exploited for treating atherosclerosis. © 2016 American Heart Association, Inc.

  7. Nerve Growth Factor Regulates Transient Receptor Potential Vanilloid 2 via Extracellular Signal-Regulated Kinase Signaling To Enhance Neurite Outgrowth in Developing Neurons.

    Science.gov (United States)

    Cohen, Matthew R; Johnson, William M; Pilat, Jennifer M; Kiselar, Janna; DeFrancesco-Lisowitz, Alicia; Zigmond, Richard E; Moiseenkova-Bell, Vera Y

    2015-12-01

    Neurite outgrowth is key to the formation of functional circuits during neuronal development. Neurotrophins, including nerve growth factor (NGF), increase neurite outgrowth in part by altering the function and expression of Ca(2+)-permeable cation channels. Here we report that transient receptor potential vanilloid 2 (TRPV2) is an intracellular Ca(2+)-permeable TRPV channel upregulated by NGF via the mitogen-activated protein kinase (MAPK) signaling pathway to augment neurite outgrowth. TRPV2 colocalized with Rab7, a late endosome protein, in addition to TrkA and activated extracellular signal-regulated kinase (ERK) in neurites, indicating that the channel is closely associated with signaling endosomes. In line with these results, we showed that TRPV2 acts as an ERK substrate and identified the motifs necessary for phosphorylation of TRPV2 by ERK. Furthermore, neurite length, TRPV2 expression, and TRPV2-mediated Ca(2+) signals were reduced by mutagenesis of these key ERK phosphorylation sites. Based on these findings, we identified a previously uncharacterized mechanism by which ERK controls TRPV2-mediated Ca(2+) signals in developing neurons and further establish TRPV2 as a critical intracellular ion channel in neuronal function. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  8. cAMP response element-binding protein and Yes-associated protein form a feedback loop that promotes neurite outgrowth.

    Science.gov (United States)

    Chen, Lei; Feng, Peimin; Peng, Anjiao; Qiu, Xiangmiao; Zhu, Xi; He, Shixu; Zhou, Dong

    2017-08-31

    The cAMP response element-binding (CREB) protein is a member of the CREB/activating transcription factor family that is activated by various extracellular stimuli. It has been shown that CREB-dependent transcription stimulation plays a key role in neuronal differentiation and plasticity, but the underlying mechanisms remain largely elusive. Here, we show that Yes-associated protein (YAP) is a direct target induced by CREB upon retinoic acid (RA)-induced neurite outgrowth stimuli in N2a cells. Interestingly, YAP knockout using the CRISPR/Cas9 system inhibits neuronal differentiation and reduced neurite length. We further show that YAP could directly bind to CREB via its N-terminal region, and loss of YAP results in instability of phosphorylated CREB upon neurite outgrowth stimuli. Transient expression of YAP could largely restore CREB expression and neurite outgrowth in YAP knockout cells. Together, our results suggest that CREB and YAP form a positive feedback loop that is critical to maintain the stability of phosphorylated CREB and promote neurite outgrowth. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  9. Review: Mechanical Characterization of Carotid Arteries and Atherosclerotic Plaques.

    Science.gov (United States)

    de Korte, Chris L; Fekkes, Stein; Nederveen, Aart J; Manniesing, Rashindra; Hansen, Hendrik Rik H G

    2016-10-01

    Cardiovascular disease (CVD) is a leading cause of death and is in the majority of cases due to the formation of atherosclerotic plaques in arteries. Initially, thickening of the inner layer of the arterial wall occurs. Continuation of this process leads to plaque formation. The risk of a plaque to rupture and thus to induce an ischemic event is directly related to its composition. Consequently, characterization of the plaque composition and its proneness to rupture are of crucial importance for risk assessment and treatment strategies. The carotid is an excellent artery to be imaged with ultrasound because of its superficial position. In this review, ultrasound-based methods for characterizing the mechanical properties of the carotid wall and atherosclerotic plaque are discussed. Using conventional echography, the intima media thickness (IMT) can be quantified. There is a wealth of studies describing the relation between IMT and the risk for myocardial infarction and stroke. Also the carotid distensibility can be quantified with ultrasound, providing a surrogate marker for the cross-sectional mechanical properties. Although all these parameters are associated with CVD, they do not easily translate to individual patient risk. Another technique is pulse wave velocity (PWV) assessment, which measures the propagation of the pressure pulse over the arterial bed. PWV has proven to be a marker for global arterial stiffness. Recently, an ultrasound-based method to estimate the local PWV has been introduced, but the clinical effectiveness still needs to be established. Other techniques focus on characterization of plaques. With ultrasound elastography, the strain in the plaque due to the pulsatile pressure can be quantified. This technique was initially developed using intravascular catheters to image coronaries, but recently noninvasive methods were successfully developed. A high correlation between the measured strain and the risk for rupture was established. Acoustic

  10. Maternal obesity and IL-6 lead to aberrant developmental gene expression and deregulated neurite growth in the fetal arcuate nucleus.

    Science.gov (United States)

    Sanders, Tessa R; Kim, Dong Won; Glendining, Kelly A; Jasoni, Christine L

    2014-07-01

    Maternal obesity during pregnancy increases the risk of obesity in the offspring. Several observations have pointed to a causative role for the proinflammatory cytokine IL-6, but whether it is present in the fetal circulation and how it acts on the developing fetus are unclear. We first observed that postnatal day 0 offspring from obese mothers had significantly reduced neuropeptide Y (NPY) innervation of the paraventricular nucleus (PVN) compared with that for offspring of normal-weight controls. Thus, the growth of NPY neurites from the arcuate nucleus (ARC) was impaired in the fetal brain by maternal obesity. The neurite growth regulator, Netrin-1, was expressed in the ARC and PVN and along the pathway between the two at gestational day (GD) 17.5 in normal animals, making it likely to be involved in the development of NPY ARC-PVN projections. In addition, the expression of Dcc and Unc5d, receptors for Netrin-1, were altered in the GD17.5 ARC in obese but not normal weight pregnancies. Thus, this important developmental pathway is perturbed by maternal obesity and may explain the defect in NPY innervation of the PVN that occurs in fetuses developing in obese mothers. To investigate whether IL-6 may play a role in these developmental changes, we found first that IL-6 was significantly elevated in the fetal and maternal circulation in pregnancies of obese mice compared with those of normal-weight mice. In addition, treatment of GD17.5 ARC tissue with IL-6 in vitro significantly reduced ARC neurite outgrowth and altered developmental gene expression similar to maternal obesity in vivo. These findings demonstrate that maternal obesity may alter the way in which fetal ARC NPY neurons respond to key developmental signals that regulate normal prenatal neural connectivity and suggest a causative role for elevated IL-6 in these changes.

  11. Involvement of gecko SNAP25b in spinal cord regeneration by promoting outgrowth and elongation of neurites.

    Science.gov (United States)

    Wang, Yingjie; Dong, Yingying; Song, Honghua; Liu, Yan; Liu, Mei; Yuan, Ying; Ding, Fei; Gu, Xiaosong; Wang, Yongjun

    2012-12-01

    SNARE complex mediates cellular membrane fusion events essential for neurotransmitter release and synaptogenesis. SNAP25, a member of the SNARE proteins, plays critical roles during the development of the central nervous system via regulation by alternative splicing and protein kinase phosphorylation. To date, little information is available regarding the protein in the spinal cord regeneration, especially for the postnatal highly expressed isoform SNAP25b. In the present study, we characterized gecko SNAP25b, which shared high identity with those of other vertebrates. Expression of gecko SNAP25b was temporally upregulated in both neurons of spinal cord and forming ependymal tube following tail amputation, coinciding with the occurrence of regenerate re-innervation. Overexpression of gecko wild type SNAP25b in the SH-SY5Y and undifferentiated PC12 cells promoted the elongation and outgrowth of neurites, while mutant constructs at Serine(187) resulted in differential effects for which S187A had a promoting role. Knockdown of endogenous SNAP25b affected the formation of neurites, which could be rescued by overexpression of SNAP25b. FM1-43 staining revealed that transfection of S187E mutant construct reduced the recruitment of vesicles. In addition, transfection of gecko SNAP25b in the astrocyte, which is absent from neuronal specific VAMP2, was capable of enhancing process elongation, indicating a potential for various alternative protein combinations. Taken together, our data suggest that gecko SNAP25b is involved in spinal cord regeneration by promoting outgrowth and elongation of neurites in a more extensive protein binding manner. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Antiinflammatory actions of inorganic nitrate stabilize the atherosclerotic plaque

    Science.gov (United States)

    Khambata, Rayomand S.; Ghosh, Suborno M.; Rathod, Krishnaraj S.; Thevathasan, Tharssana; Filomena, Federica; Xiao, Qingzhong; Ahluwalia, Amrita

    2017-01-01

    Reduced bioavailable nitric oxide (NO) plays a key role in the enhanced leukocyte recruitment reflective of systemic inflammation thought to precede and underlie atherosclerotic plaque formation and instability. Recent evidence demonstrates that inorganic nitrate (NO3−) through sequential chemical reduction in vivo provides a source of NO that exerts beneficial effects upon the cardiovascular system, including reductions in inflammatory responses. We tested whether the antiinflammatory effects of inorganic nitrate might prove useful in ameliorating atherosclerotic disease in Apolipoprotein (Apo)E knockout (KO) mice. We show that dietary nitrate treatment, although having no effect upon total plaque area, caused a reduction in macrophage accumulation and an elevation in smooth muscle accumulation within atherosclerotic plaques of ApoE KO mice, suggesting plaque stabilization. We also show that in nitrate-fed mice there is reduced systemic leukocyte rolling and adherence, circulating neutrophil numbers, neutrophil CD11b expression, and myeloperoxidase activity compared with wild-type littermates. Moreover, we show in both the ApoE KO mice and using an acute model of inflammation that this effect upon neutrophils results in consequent reductions in inflammatory monocyte expression that is associated with elevations of the antiinflammatory cytokine interleukin (IL)-10. In summary, we demonstrate that inorganic nitrate suppresses acute and chronic inflammation by targeting neutrophil recruitment and that this effect, at least in part, results in consequent reductions in the inflammatory status of atheromatous plaque, and suggest that this effect may have clinical utility in the prophylaxis of inflammatory atherosclerotic disease. PMID:28057862

  13. Statins, atherosclerosis regression and HDL: Insights from within the plaque.

    Science.gov (United States)

    Feig, Jonathan E; Feig, Jessica L; Kini, Annapoorna S

    2015-06-15

    The idea that atheroma can regress is no longer a dream. We and others have discovered that decreasing the lipid content can directly lead to macrophage egress and plaque healing. The question, however, has remained as to how to translate these findings to the bedside. Taking advantage of imaging modalities such as intravascular ultrasound (IVUS) and near infrared spectroscopy (NIRS), we demonstrated in the YELLOW (Reduction in Yellow Plaque by Intensive Lipid Lowering Therapy) trial that short term treatment of high dose rosuvastatin treatment can lead to a decrease in lipid content in plaques. It is important to note that optical coherence tomography (OCT), a high resolution imaging modality, was not performed during the first study and therefore, only a very limited assessment of the effect of statin therapy on measures of plaque stabilization could be made. The YELLOW II trial is the first to our knowledge to determine whether these data can be extrapolated and how it relates to HDL function, alterations in macrophage gene expression, and plaque morphology. While tremendous progress has been made, our research serves as a reminder that angiography is simply luminography and it is features such as thin cap fibroatheroma and lipid burden, for example, that likely modulate the syndromes seen in clinical practice. Ongoing studies such as ours may provide novel pathways for diagnosis and therapy, with the ultimate goal of reducing the burden of cardiovascular disease. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Early dental plaque formation on toothbrushed titanium implant surfaces.

    Science.gov (United States)

    Amarante, Evandro Scligliano; Chambrone, Leandro; Lotufo, Roberto Fraga Moreira; Lima, Luiz A

    2008-10-01

    To evaluate the qualitative and quantitative differences on dental plaque formation on two different roughness titanium implant surfaces, i.e. machined and titanium plasma sprayed, as well as the amount of plaque removal by regular toothbrushing after 72-hour plaque accumulation. Eight systemically healthy subjects were recruited from the patient pool of a private dental practice. All patients underwent oral hygiene instruction and full mouth prophylaxis. Subsequently, maxillary casts from all patients were obtained and removable 0.7 mm-thick acetate stents without occlusal contact points were fabricated to support four titanium specimens of 4 x 2 x 2 mm divided into two groups (machined and plasma sprayed). Subjects were instructed to wear the stents for 72 hours, full time, removing them only during regular oral hygiene. Subsequently, the appliances were immediately repositioned and then the test side was brushed for 20 seconds. At the end of the 72-hour period, the stents were removed and prepared for microbiological analysis. Both machined and plasma sprayed brushed surfaces presented statistically significant fewer bacteria than non-brushed surfaces. Similarly, regarding surface roughness, machined surfaces presented a total number of bacteria significantly smaller than those presented by plasma sprayed surfaces (P dental plaque than polished surfaces. Both brushed surfaces presented less plaque accumulation, however, implant brushing was more effective on machined surfaces.

  15. Uniaxial tensile testing approaches for characterisation of atherosclerotic plaques.

    Science.gov (United States)

    Walsh, M T; Cunnane, E M; Mulvihill, J J; Akyildiz, A C; Gijsen, F J H; Holzapfel, G A

    2014-03-03

    The pathological changes associated with the development of atherosclerotic plaques within arterial vessels result in significant alterations to the mechanical properties of the diseased arterial wall. There are several methods available to characterise the mechanical behaviour of atherosclerotic plaque tissue, and it is the aim of this paper to review the use of uniaxial mechanical testing. In the case of atherosclerotic plaques, there are nine studies that employ uniaxial testing to characterise mechanical behaviour. A primary concern regarding this limited cohort of published studies is the wide range of testing techniques that are employed. These differing techniques have resulted in a large variance in the reported data making comparison of the mechanical behaviour of plaques from different vasculatures, and even the same vasculature, difficult and sometimes impossible. In order to address this issue, this paper proposes a more standardised protocol for uniaxial testing of diseased arterial tissue that allows for better comparisons and firmer conclusions to be drawn between studies. To develop such a protocol, this paper reviews the acquisition and storage of the tissue, the testing approaches, the post-processing techniques and the stress-strain measures employed by each of the nine studies. Future trends are also outlined to establish the role that uniaxial testing can play in the future of arterial plaque mechanical characterisation. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

    Taggart, M.A. [School of Biological Sciences, University of Aberdeen, Cruickshank Bld, St Machar Drive, Aberdeen, AB24 3UU (United Kingdom); Instituto de Investigacion en Recursos Cinegeticos, IREC (CSIC-UCLM-JCCM), Ronda de Toledo s/n, 13005 Ciudad Real (Spain)], E-mail: mark.taggart@uclm.es; Mateo, R. [Instituto de Investigacion en Recursos Cinegeticos, IREC (CSIC-UCLM-JCCM), Ronda de Toledo s/n, 13005 Ciudad Real (Spain); Charnock, J.M.; Bahrami, F. [Synchrotron Radiation Department, CCLRC Daresbury Laboratory, Warrington, Cheshire, WA4 4AD (United Kingdom); Green, A.J. [Department of Wetland Ecology, Estacion Biologica de Donana, CSIC, Pabellon del Peru, Avenida Maria Luisa s/n, 41013 Seville (Spain); Meharg, A.A. [School of Biological Sciences, University of Aberdeen, Cruickshank Bld, St Machar Drive, Aberdeen, AB24 3UU (United Kingdom)

    2009-03-15

    Arsenic is known to accumulate with iron plaque on macrophyte roots. Three to four years after the Aznalcollar 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{sup -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 Aznalcollar spill are shown to have elevated levels of arsenic in their feces, which may originate from arsenic rich iron plaque. - Accumulation of metals with iron plaque on macrophyte roots in wetlands poses an ecotoxicological risk to certain herbivores.

  17. Infliximab in the treatment of plaque type psoriasis

    Directory of Open Access Journals (Sweden)

    Rosita Saraceno

    2009-04-01

    Full Text Available Rosita Saraceno, Andrea Saggini, Lucia Pietroleonardo, Sergio ChimentiDepartment of Dermatology, University of Rome Tor Vergata, Rome, Viale Oxford 81, Rome, ItalyAbstract: Psoriasis is a chronic and immunomediated skin disease characterized by erythematous scaly plaques. Psoriasis affects approximately 1% to 3% of the Caucasian population. Tumor necrosis factor alpha (TNF-α is a proinflammatory cytokine that plays a critical role in the pathogenesis of psoriasis. Infliximab is an anti-TNF-α drug widely used for the treatment of plaque type psoriasis and psoriatic arthritis. Controlled clinical trials demonstrated that infliximab is characterized by a high degree of clinical response in moderate to severe plaque psoriasis. Moreover infliximab showed rapid efficacy in nail psoriasis which represents a therapeutic challenge for dermatologists and a relevant source of distress for patients with plaque psoriasis. This anti-TNF-α has an encouraging safety profile, especially as long as physicians are watchful in prevention and early diagnosis of infections and infuse reactions. The efficacy, tolerability and safety profiles suggest infliximab as a suitable anti-psoriatic drug in the long-term treatment of a chronic disease such as plaque-type psoriasis.Keywords: psoriasis, nail psoriasis, infliximab, long-term treatment

  18. Neuronal activity and amyloid plaque pathology: an update.

    Science.gov (United States)

    Ovsepian, Saak V; O'Leary, Valerie B

    2016-01-01

    A breakthrough in Alzheimer's disease (AD) research came with the discovery of the link between activity-dependent release of amyloid-β (Aβ) from neurons and formation of amyloid plaques. Along with elucidating the cellular basis of behavioral-dependent fluctuations in Aβ levels in the brain, insights have been gained toward understanding the mechanisms that warrant selective vulnerability of various forebrain circuits to amyloid pathology. The notion of elevated activity as a source of excessive Aβ production and plaque formation is, however, in conflict with ample electrophysiological data, which demonstrate exceedingly intense activity (both intrinsic and synaptic) of neurons in several brain regions that are spared or marginally affected by amyloid plaques of AD. Thus, the link between the functional load of brain circuits and their vulnerability to amyloidosis, while evident, is also complex and remains poorly understood. Here, we discuss emerging data suggestive of a major role for super-intense synchronous activity of cortical and limbic networks in excessive Aβ production and plaque formation. It is proposed that dense recurrent wiring of associative areas prone to epileptic seizures might be of critical relevance to their higher susceptibility to plaque pathology and related functional impairments.

  19. Clinicomicrobiological Evaluation of 2% Chitosan Mouthwashes on Dental Plaque.

    Science.gov (United States)

    Mhaske, Sheetal P; Ambiti, Rajesh; Jagga, Umang; Paul, Uttam; Shanmukappa, Shruthi M; Iska, Divya

    2018-01-01

    This study was conducted to evaluate microbiological and clinical effects of a chitosan chlorhexidine (CH) mouthrinse on plaque control. Subjects were divided into three groups. Group I included 15 subjects who used 0.2% chlorhexidine digluconate (CHX), group II included 15 subjects who used 2% chitosan (CH) solution, and group III involves 15 subjects who used 0.2% chlorhexidine/2% CH combination. Plaque index (PI), gingival index (GI), and probing depth (PD) were recorded at the baseline, on day 0, and after 4 days. Supragingival plaque samples were subjected for microbiological evaluation. Statistical analysis was done using statistical software IBM Statistical Package for the Social Sciences (SPSS), version 21. Plaque index was lowest in group I at day 0, while it was highest in group III. At day 4, PI was highest in group II, while lowest in group III. Gingival index was lowest in group I and highest in group II at day 0, and lowest in group I and highest in group III at day 4. There was no statistical difference in Streptococcus mutans (S. mutans) count between groups at any time interval. Both chitosan and CH were found to be effective in controlling plaque. However, a combination of both provides even better results. The present study showed that chitosan can be used as an antiplaque agent.

  20. The effect of chewing gum on dental plaque accumulation

    Directory of Open Access Journals (Sweden)

    Karami Nogourani M

    2010-06-01

    Full Text Available "nBackground and Aims: Studies show that sucrose containing chewing gums are cariogenic. The aim of this study was to evaluate the effect of two commercial chewing gums with and without sucrose on dental plaque accumulation compared with the control group. "nMaterials and Methods: In this clinical study, plaque accumulation during three 7-day periods (with two weeks interval was recorded (Sillness & Loe Index in a group of 23 volunteer male dental students who chewed in the first two periods sugar-free or sugar-containing chewing gums (Olips and Orbit, respectively and in the last period did not chew any gum. Participants were asked to chew daily five gum sticks after meals for about twenty minutes. The data were statistically analyzed using Repeated Measure ANOVA and paired-T test. "nResults: The results showed that chewing any gum even sucrose-containing gum decreased the level of dental plaque accumulation (P<0.001. However, the decreasing effect of sugar-free gums was significantly higher (P<0.001. "nConclusion: Although sugar free gum was more effective than sugar containing gum on reducing dental plaque accumulation, chewing even sugar containing gums could decrease the level of dental plaque.

  1. Low copper and high manganese levels in prion protein plaques

    Science.gov (United States)

    Johnson, Christopher J.; Gilbert, P.U.P.A.; Abrecth, Mike; Baldwin, Katherine L.; Russell, Robin E.; Pedersen, Joel A.; McKenzie, Debbie

    2013-01-01

    Accumulation of aggregates rich in an abnormally folded form of the prion protein characterize the neurodegeneration caused by transmissible spongiform encephalopathies (TSEs). The molecular triggers of plaque formation and neurodegeneration remain unknown, but analyses of TSE-infected brain homogenates and preparations enriched for abnormal prion protein suggest that reduced levels of copper and increased levels of manganese are associated with disease. The objectives of this study were to: (1) assess copper and manganese levels in healthy and TSE-infected Syrian hamster brain homogenates; (2) determine if the distribution of these metals can be mapped in TSE-infected brain tissue using X-ray photoelectron emission microscopy (X-PEEM) with synchrotron radiation; and (3) use X-PEEM to assess the relative amounts of copper and manganese in prion plaques in situ. In agreement with studies of other TSEs and species, we found reduced brain levels of copper and increased levels of manganese associated with disease in our hamster model. We also found that the in situ levels of these metals in brainstem were sufficient to image by X-PEEM. Using immunolabeled prion plaques in directly adjacent tissue sections to identify regions to image by X-PEEM, we found a statistically significant relationship of copper-manganese dysregulation in prion plaques: copper was depleted whereas manganese was enriched. These data provide evidence for prion plaques altering local transition metal distribution in the TSE-infected central nervous system.

  2. Effect of baking soda in dentifrices on plaque removal.

    Science.gov (United States)

    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.

  3. Neto2 Assembles with Kainate Receptors in DRG Neurons during Development and Modulates Neurite Outgrowth in Adult Sensory Neurons.

    Science.gov (United States)

    Vernon, Claire G; Swanson, Geoffrey T

    2017-03-22

    Peripheral sensory neurons in the dorsal root ganglia (DRG) are the initial transducers of sensory stimuli, including painful stimuli, from the periphery to central sensory and pain-processing centers. Small- to medium-diameter non-peptidergic neurons in the neonatal DRG express functional kainate receptors (KARs), one of three subfamilies of ionotropic glutamate receptors, as well as the putative KAR auxiliary subunit Neuropilin- and tolloid-like 2 (Neto2). Neto2 alters recombinant KAR function markedly but has yet to be confirmed as an auxiliary subunit that assembles with and alters the function of endogenous KARs. KARs in neonatal DRG require the GluK1 subunit as a necessary constituent, but it is unclear to what extent other KAR subunits contribute to the function and proposed roles of KARs in sensory ganglia, which include promotion of neurite outgrowth and modulation of glutamate release at the DRG-dorsal horn synapse. In addition, KARs containing the GluK1 subunit are implicated in modes of persistent but not acute pain signaling. We show here that the Neto2 protein is highly expressed in neonatal DRG and modifies KAR gating in DRG neurons in a developmentally regulated fashion in mice. Although normally at very low levels in adult DRG neurons, Neto2 protein expression can be upregulated via MEK/ERK signaling and after sciatic nerve crush and Neto2 -/- neurons from adult mice have stunted neurite outgrowth. These data confirm that Neto2 is a bona fide KAR auxiliary subunit that is an important constituent of KARs early in sensory neuron development and suggest that Neto2 assembly is critical to KAR modulation of DRG neuron process outgrowth. SIGNIFICANCE STATEMENT Pain-transducing peripheral sensory neurons of the dorsal root ganglia (DRG) express kainate receptors (KARs), a subfamily of glutamate receptors that modulate neurite outgrowth and regulate glutamate release at the DRG-dorsal horn synapse. The putative KAR auxiliary subunit Neuropilin- and

  4. TSP-1 secreted by bone marrow stromal cells contributes to retinal ganglion cell neurite outgrowth and survival.

    Directory of Open Access Journals (Sweden)

    Keming Yu

    Full Text Available BACKGROUND: Bone marrow stromal cells (BMSCs are pluripotent and thereby a potential candidate for cell replacement therapy for central nervous system degenerative disorders and traumatic injury. However, the mechanism of their differentiation and effect on neural tissues has not been fully elucidated. This study evaluates the effect of BMSCs on neural cell growth and survival in a retinal ganglion cell (RGCs model by assessing the effect of changes in the expression of a BMSC-secreted protein, thrombospondin-1 (TSP-1, as a putative mechanistic agent acting on RGCs. METHODS AND FINDINGS: The effect of co-culturing BMSCs and RGCs in vitro was evaluated by measuring the following parameters: neurite outgrowth, RGC survival, BMSC neural-like differentiation, and the effect of TSP-1 on both cell lines under basal secretion conditions and when TSP-1 expression was inhibited. Our data show that BMSCs improved RGC survival and neurite outgrowth. Synaptophysin, MAP-2, and TGF-beta expression are up-regulated in RGCs co-cultured with BMSCs. Interestingly, the BMSCs progressively displayed neural-like morphology over the seven-day study period. Restriction display polymerase chain reaction (RD-PCR was performed to screen for differentially expressed genes in BMSCs cultured alone or co-cultured with RGCs. TSP-1, a multifactorial extracellular matrix protein, is critically important in the formation of neural connections during development, so its function in our co-culture model was investigated by small interfering RNA (siRNA transfection. When TSP-1 expression was decreased with siRNA silencing, BMSCs had no impact on RGC survival, but reduced neurite outgrowth and decreased expression of synaptophysin, MAP-2 and TGF-beta in RGCs. Furthermore, the number of BMSCs with neural-like characteristics was significantly decreased by more than two-fold using siRNA silencing. CONCLUSIONS: Our data suggest that the TSP-1 signaling pathway might have an important

  5. Altered neurite morphology and cholinergic function of induced pluripotent stem cell-derived neurons from a patient with Kleefstra syndrome and autism

    Science.gov (United States)

    Nagy, J; Kobolák, J; Berzsenyi, S; Ábrahám, Z; Avci, H X; Bock, I; Bekes, Z; Hodoscsek, B; Chandrasekaran, A; Téglási, A; Dezső, P; Koványi, B; Vörös, E T; Fodor, L; Szél, T; Németh, K; Balázs, A; Dinnyés, A; Lendvai, B; Lévay, G; Román, V

    2017-01-01

    The aim of the present study was to establish an in vitro Kleefstra syndrome (KS) disease model using the human induced pluripotent stem cell (hiPSC) technology. Previously, an autism spectrum disorder (ASD) patient with Kleefstra syndrome (KS-ASD) carrying a deleterious premature termination codon mutation in the EHMT1 gene was identified. Patient specific hiPSCs generated from peripheral blood mononuclear cells of the KS-ASD patient were differentiated into post-mitotic cortical neurons. Lower levels of EHMT1 mRNA as well as protein expression were confirmed in these cells. Morphological analysis on neuronal cells differentiated from the KS-ASD patient-derived hiPSC clones showed significantly shorter neurites and reduced arborization compared to cells generated from healthy controls. Moreover, density of dendritic protrusions of neuronal cells derived from KS-ASD hiPSCs was lower than that of control cells. Synaptic connections and spontaneous neuronal activity measured by live cell calcium imaging could be detected after 5 weeks of differentiation, when KS-ASD cells exhibited higher sensitivity of calcium responses to acetylcholine stimulation indicating a lower nicotinic cholinergic tone at baseline condition in KS-ASD cells. In addition, gene expression profiling of differentiated neuronal cells from the KS-ASD patient revealed higher expression of proliferation-related genes and lower mRNA levels of genes involved in neuronal maturation and migration. Our data demonstrate anomalous neuronal morphology, functional activity and gene expression in KS-ASD patient-specific hiPSC-derived neuronal cultures, which offers an in vitro system that contributes to a better understanding of KS and potentially other neurodevelopmental disorders including ASD. PMID:28742076

  6. Gene expression and 18FDG uptake in atherosclerotic carotid plaques

    DEFF Research Database (Denmark)

    Pedersen, Sune Folke; Græbe, Martin; Hag, Anne Mette Fisker

    2010-01-01

    by carotid endarterectomy. The gene expression of markers of vulnerability - CD68, IL-18, matrix metalloproteinase 9, cathepsin K, GLUT-1, and hexokinase type II (HK2) - were measured in plaques by quantitative PCR. RESULTS: In a multivariate linear regression model, GLUT-1, CD68, cathepsin K, and HK2 gene......) and an additional ipsilateral internal carotid artery stenosis of greater than 60% were recruited. FDG uptake in the carotids was determined by PET/computed tomography and expressed as mean and maximal standardized uptake values (SUVmean and SUVmax). The atherosclerotic plaques were subsequently recovered...... destabilization. Accordingly, FDG-PET could prove to be an important predictor of cerebrovascular events in patients with carotid plaques....

  7. Apremilast for the management of moderate to severe plaque psoriasis.

    Science.gov (United States)

    Vangipuram, Ramya; Alikhan, Ali

    2017-04-01

    Psoriasis is a chronic inflammatory skin disease characterized by erythematous plaques on extensor surfaces, scalp, and back. Current therapies for psoriasis are limited by route of administration, side effects, and cost. Apremilast is the first oral phosphodiesterase inhibitor approved for moderate-to-severe plaque psoriasis. It is a small molecule inhibitor of phosphodiesterase-4, and decreases the inflammatory activity associated with psoriasis. Areas covered: This review will discuss the pharmacology of apremilast, mechanism of action, results from key clinical trials, and its use in managing psoriasis. Currently approved treatments are also discussed. Expert commentary: The advantages of apremilast include convenient oral administration and dosing, a favorable safety and tolerability profile, and significant efficacy in moderate-to-severe plaque psoriasis.

  8. Radiation regression patterns after cobalt plaque insertion for retinoblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Buys, R.J.; Abramson, D.H.; Ellsworth, R.M.; Haik, B.

    1983-08-01

    An analysis of 31 eyes of 30 patients who had been treated with cobalt plaques for retinoblastoma disclosed that a type I radiation regression pattern developed in 15 patients; type II, in one patient, and type III, in five patients. Nine patients had a regression pattern characterized by complete destruction of the tumor, the surrounding choroid, and all of the vessels in the area into which the plaque was inserted. This resulting white scar, corresponding to the sclerae only, was classified as a type IV radiation regression pattern. There was no evidence of tumor recurrence in patients with type IV regression patterns, with an average follow-up of 6.5 years, after receiving cobalt plaque therapy. Twenty-nine of these 30 patients had been unsuccessfully treated with at least one other modality (ie, light coagulation, cryotherapy, external beam radiation, or chemotherapy).

  9. Tools for improving the diagnosis of atherosclerotic plaque using ultrasound

    DEFF Research Database (Denmark)

    Jespersen, Søren Kragh

    1997-01-01

    , named ``XTRA'', has been designed, implemented, tested, and subsequently used for \\emph{in vitro} investigation of the MACI technique. The MACI method has been investigated on various tissue mimicking phantoms, on porcine tissue samples and on human carotid plaque specimens. Generally, the results show....... An increase of 30% in the axial width and 10% in the lateral width of the PSF was found, thus, the point resolution capability is only reduced marginally. Visualization of tissue interfaces was investigated using rubber tube phantoms, porcine aorta, and human plaque specimens. The MACI images show improved...... of eight regions were detectable when using MACI, compared to only three out of eight when using conventional B-mode imaging. Finally, two human carotid plaque specimens were scanned in 3D (by mechanical movement of the transducer in one direction). The MACI images were subjectively found to give a more...

  10. Reproducibility of Two 3-D Ultrasound Carotid Plaque Quantification Methods

    DEFF Research Database (Denmark)

    Graebe, Martin; Entrekin, Robert; Collet-Billon, Antoine

    2014-01-01

    Compared with single 2-D images, emerging 3-D ultrasound technologies hold the promise of reducing variability and increasing sensitivity in the quantification of carotid plaques for individual cardiovascular risk stratification. Inter- and intra-observer agreement between a manual, cross......-sectional, 2-D freehand sweep and a mechanical 3-D ultrasound investigation of 62 carotid artery plaques is reported with intra-class correlation coefficients (with 95% confidence intervals). Inter-observer agreement was 0.60 (0.29-0.77) for the freehand method and 0.89 (0.83-0.93) for the mechanical 3-D...... acquisition. The use of semi-automated computerized planimetric measurements of plaque burden has high intra-observer repeatability, but is vulnerable to systematic inter-observer differences. For the 2-D freehand sweep, a considerable contribution to variation is introduced by the scanning procedure itself...

  11. Regression of posterior uveal melanomas following cobalt-60 plaque radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Cruess, A.F.; Augsburger, J.J.; Shields, J.A.; Brady, L.W.; Markoe, A.M.; Day, J.L.

    1984-12-01

    A method has been devised for evaluating the rate and extent of regression of the first 100 consecutive patients with a posterior uveal melanoma that had been managed by Cobalt-60 plaque radiotherapy at Wills Eye Hospital. It was found that the average posterior uveal melanoma in the series did not regress rapidly to a flat, depigmented scar but shrank slowly and persisted as a residual mass approximately 50% of the thickness of the original tumor at 54 months following Cobalt-60 plaque radiotherapy. The authors also found that the rate and extent of regression of the tumors in patients who subsequently developed metastatic melanoma were not appreciably different from the rate and extent of regression of the tumors in patients who remained well systemically. These observations indicate that the rate and extent of regression of posterior uveal melanomas following Cobalt-60 plaque radiotherapy are poor indicators of the prognosis of the affected patients for subsequent development of clinical metastatic disease.

  12. The prognostic role of carotid plaque ultrasonography in cardiac damage after carotid endarterectomy: carotid plaque and cardiac risk.

    Science.gov (United States)

    Galyfos, George; Toutouzas, Konstantinos P; Benetos, George; Konstadoulakis, Manousos; Theodorou, Dimitrios; Katsaragakis, Stilianos; Stefanadis, Christodoulos; Zografos, Georgios; Filis, Konstantinos

    2016-10-01

    This study evaluates the correlation of ultrasound determined carotid plaque morphology with coronary risk and cardiac damage after carotid endarterectomy. Fifty patients (in a series of 162) scheduled for carotid endarterectomy had the indication for coronary CT-angiography preoperatively and were included in this study. Patients were classified according to ultrasonographic characteristics of carotid plaque. The Duke Criteria were used to assess the degree of coronary risk (low, medium and high risk). Cardiac damage after carotid endarterectomy was evaluated based on symptoms, cardiac Troponin I measurement and electrocardiographic findings. There were no deaths, strokes or symptomatic myocardial infarctions postoperatively (30-day results). Ten patients (20%) showed asymptomatic cardiac damage postoperatively. Cardiac damage after surgery did not show any difference between the three cardiac risk groups. Echogenic and specifically Type IV carotid artery plaques (Gray-Weale Criteria) were associated with high cardiac risk preoperatively and with postoperative cardiac damage. The degree of carotid artery stenosis, and echolucent carotid plaques were not associated with postoperative cardiac damage. Asymptomatic postoperative cardiac damage occurs often after carotid endarterectomy and presents independently from coronary risk. Carotid plaques of higher echogenicity are associated with severity of coronary artery disease and cardiac damage after carotid endarterectomy.

  13. Short-term consumption of probiotic lactobacilli has no effect on acid production of supragingival plaque

    DEFF Research Database (Denmark)

    Marttinen, Aino; Haukioja, Anna; Karjalainen, Sára

    2011-01-01

    analysis of plaque revealed the presence of LGG in four and L. reuteri in six subjects after the use of the probiotic. The use of the lactobacilli did not affect the acidogenicity or MS levels of plaque. Short-term consumption of LGG and L. reuteri appeared not to influence the acidogenicity of plaque....... of probiotics to the plaque was assessed using PCR techniques. No probiotic-induced changes were found in the acidogenicity of plaque. Also, MS counts remained at the original level. The number of subjects with lactobacilli in plaque increased in the L. reuteri group (p¿=¿0.011) but not in the LGG group. PCR...

  14. Plaque and gingivitis in the deciduous and permanent dentition.

    Science.gov (United States)

    Ramberg, P W; Lindhe, J; Gaffar, A

    1994-08-01

    The aim of the present investigation was to monitor de novo plaque formation and associated alterations of the gingival conditions in the deciduous, mixed and permanent dentition in man. 31 volunteers, divided into 3 study groups participated in the trial. Group 1 was made up of 11 subjects, 4-6 years of age (deciduous dentition), group 2 comprised of 10 subjects, 8-9 years of age (mixed dentition) and group 3 included 10 subjects, 14-16 years of age (permanent dentition). After a screening examination, each participant received detailed instruction in a proper oral hygiene technique and was subjected to professional tooth cleaning. The professional debridement and the oral hygiene instruction were repeated after 1 week. After another week, a given day was termed Day 0 and a baseline examination was performed. This examination included assessments of plaque and gingivitis. Each subject received an additional, comprehensive professional tooth cleaning and was asked to abstain from all mechanical oral hygiene measures. Re-examinations were performed after 3 and 7 days. The findings demonstrated that: (i) during a 7-day period of no active oral hygiene, subjects with a mixed or a permanent dentition formed visible amounts of plaque and developed modest signs of gingivitis; (ii) during the 7 days of the trial, young subjects with a fully erupted deciduous dentition formed less plaque than the older subjects, and failed to respond to de novo plaque formation with enhanced signs of gingivitis; (iii) in subjects with a mixed dentition, the amount of plaque formed during the 7 days of experiment and the matching gingivitis development were similar in the deciduous and permanent tooth segments of the dentition.

  15. Road density

    Data.gov (United States)

    U.S. Environmental Protection Agency — Road density is generally highly correlated with amount of developed land cover. High road densities usually indicate high levels of ecological disturbance. More...

  16. Optimized Culture System to Induce Neurite Outgrowth From Retinal Ganglion Cells in Three-Dimensional Retinal Aggregates Differentiated From Mouse and Human Embryonic Stem Cells.

    Science.gov (United States)

    Maekawa, Yuki; Onishi, Akishi; Matsushita, Keizo; Koide, Naoshi; Mandai, Michiko; Suzuma, Kiyoshi; Kitaoka, Takashi; Kuwahara, Atsushi; Ozone, Chikafumi; Nakano, Tokushige; Eiraku, Mototsugu; Takahashi, Masayo

    2016-04-01

    To establish a practical research tool for studying the pathogenesis of retinal ganglion cell (RGC) diseases, we optimized culture procedures to induce neurite outgrowth from three-dimensional self-organizing optic vesicles (3D-retinas) differentiated in vitro from mouse and human embryonic stem cells (ESCs). The developing 3D-retinas isolated at various time points were placed on Matrigel-coated plates and cultured in media on the basis of the 3D-retinal culture or the retinal organotypic culture protocol. The number, length, and morphology of the neurites in each culture condition were compared. First, we confirmed that Venus-positive cells were double-labeled with a RGC marker, Brn3a, in the 3D-retina differentiated from Fstl4::Venus mouse ESCs, indicating specific RGC-subtype differentiation. Second, Venus-positive neurites grown from these RGC subsets were positive for beta-III tubulin and SMI312 by immunohistochemistry. Enhanced neurite outgrowth was observed in the B27-supplemented Neurobasal-A medium on Matrigel-coated plates from the optic vesicles isolated after 14 days of differentiation from mouse ESCs. For the differentiated RGCs from human ESCs, we obtained neurite extension of >4 mm by modifying Matrigel coating and the culture medium from the mouse RGC culture. We successfully optimized the culture conditions to enhance lengthy and high-frequency neurite outgrowth in mouse and human models. The procedure would be useful for not only developmental studies of RGCs, including maintenance and projection, but also clinical, pathological, and pharmacological studies of human RGC diseases.

  17. Multispectral optoacoustic tomography resolves smart probe activation in vulnerable plaques

    Science.gov (United States)

    Razansky, Daniel; Harlaar, Niels J.; Hillebrands, Jan-Luuk; Taruttis, Adrian; Herzog, Eva; Zeebregts, Clark; van Dam, Goitzen; Ntziachristos, Vasilis

    2011-03-01

    In this work, we show, for the first time to our knowledge, that multispectral optoacoustic tomography (MSOT) can deliver high resolution images of activatable molecular probe's distribution, sensitive to matrix metalloproteinases (MMP), deep within optically scattering human carotid specimen. It is further demonstrated that this method can be used in order to provide accurate maps of vulnerable plaque formations in atherosclerotic disease. Moreover, optoacoustic images can simultaneously show the underlining plaque morphology for accurate localization of MMP activity in three dimensions. This performance directly relates to small animal screening applications and to clinical potential as well.

  18. Atherosclerotic disease in axial spondyloarthritis: increased frequency of carotid plaques.

    Science.gov (United States)

    Rueda-Gotor, Javier; Corrales, Alfonso; Blanco, Ricardo; Fuentevilla, Patricia; Portilla, Virginia; Expósito, Rosa; Mata, Cristina; Pina, Trinitario; González-Juanatey, Carlos; Llorca, Javier; González-Gay, Miguel A

    2015-01-01

    To establish whether subclinical atherosclerosis is increased in patients with axial spondyloarthritis (ax-SpA). A set of 149 consecutive patients with no history of cardiovascular disease that fulfilled the Assessment of SpondyloArthritis International Society classification criteria for ax-SpA was studied by carotid ultrasonography. Carotid intima-media thickness (cIMT) and plaques were assessed. A series of 181 community-based controls with no cardiovascular disease were studied for comparison. To establish whether ax-SpA might have a direct effect on the risk of carotid plaques or an indirect effect via its putative influence on hypertension, dyslipidaemia or obesity, we obtained adjusted odds ratios (OR) for each clinical factor by the development of adjusted models. cIMT was increased in patients (0.621±0.123 mm) when compared to controls (0.607±0.117 mm) but the difference was not significant (p=0.30). Nevertheless, carotid plaques were more commonly observed in patients with ax-SpA than in controls (41.6% vs. 26.4%; p=0.003). Patients with plaques had longer duration of the disease than those without plaques (20.5±11.2 years vs. 12.0±8.6 years; p<0.001). Plaques were more frequent in patients with hip involvement (crude odds ratio 3.15, 95% confidence interval [CI] 1.02-9.75; p=0.05), syndesmophytes (crude OR 4.94, 95% CI 2.14-11.4; p<0.001), in patients with higher functional limitation and mobility index measured by BASFI (crude OR 1.16, 95% CI 1.02-1.33; p=0.03) and BASMI (crude OR 1.45, 95% CI 1.19-1.77; p<0.001), and in those with psoriasis (crude OR 3.94, 95% CI 1.31-11.84; p=0.02. However, except for psoriasis that continued being a strong risk factor for plaques after adjustment, the relationship between other clinical features of ax-SpA and carotid plaques disappeared in the adjusted models. Our results confirm the presence of subclinical atherosclerosis in patients with ax-SpA.

  19. ShcA regulates neurite outgrowth stimulated by neural cell adhesion molecule but not by fibroblast growth factor 2: evidence for a distinct fibroblast growth factor receptor response to neural cell adhesion molecule activation

    DEFF Research Database (Denmark)

    Hinsby, Anders M; Lundfald, Line; Ditlevsen, Dorte K

    2004-01-01

    Homophilic binding in trans of the neural cell adhesion molecule (NCAM) mediates adhesion between cells and leads, via activation of intracellular signaling cascades, to neurite outgrowth in primary neurons as well as in the neuronal cell line PC12. NCAM mediates neurite extension in PC12 cells...

  20. Kihi-to, a herbal traditional medicine, improves Abeta(25–35-induced memory impairment and losses of neurites and synapses

    Directory of Open Access Journals (Sweden)

    Joyashiki Eri

    2008-08-01

    Full Text Available Abstract Background We previously hypothesized that achievement of recovery of brain function after the injury requires the reconstruction of neuronal networks, including neurite regeneration and synapse reformation. Kihi-to is composed of twelve crude drugs, some of which have already been shown to possess neurite extension properties in our previous studies. The effect of Kihi-to on memory deficit has not been examined. Thus, the goal of the present study is to determine the in vivo and in vitro effects of Kihi-to on memory, neurite growth and synapse reconstruction. Methods Effects of Kihi-to, a traditional Japanese-Chinese traditional medicine, on memory deficits and losses of neurites and synapses were examined using Alzheimer's disease model mice. Improvements of Aβ(25–35-induced neuritic atrophy by Kihi-to and the mechanism were investigated in cultured cortical neurons. Results Administration of Kihi-to for consecutive 3 days resulted in marked improvements of Aβ(25–35-induced impairments in memory acquisition, memory retention, and object recognition memory in mice. Immunohistochemical comparisons suggested that Kihi-to attenuated neuritic, synaptic and myelin losses in the cerebral cortex, hippocampus and striatum. Kihi-to also attenuated the calpain increase in the cerebral cortex and hippocampus. When Kihi-to was added to cells 4 days after Aβ(25–35 treatment, axonal and dendritic outgrowths in cultured cortical neurons were restored as demonstrated by extended lengths of phosphorylated neurofilament-H (P-NF-H and microtubule-associated protein (MAP2-positive neurites. Aβ(25–35-induced cell death in cortical culture was also markedly inhibited by Kihi-to. Since NF-H, MAP2 and myelin basic protein (MBP are substrates of calpain, and calpain is known to be involved in Aβ-induced axonal atrophy, expression levels of calpain and calpastatin were measured. Treatment with Kihi-to inhibited the Aβ(25–35-evoked increase in

  1. Kihi-to, a herbal traditional medicine, improves Abeta(25-35)-induced memory impairment and losses of neurites and synapses.

    Science.gov (United States)

    Tohda, Chihiro; Naito, Rie; Joyashiki, Eri

    2008-08-16

    We previously hypothesized that achievement of recovery of brain function after the injury requires the reconstruction of neuronal networks, including neurite regeneration and synapse reformation. Kihi-to is composed of twelve crude drugs, some of which have already been shown to possess neurite extension properties in our previous studies. The effect of Kihi-to on memory deficit has not been examined. Thus, the goal of the present study is to determine the in vivo and in vitro effects of Kihi-to on memory, neurite growth and synapse reconstruction. Effects of Kihi-to, a traditional Japanese-Chinese traditional medicine, on memory deficits and losses of neurites and synapses were examined using Alzheimer's disease model mice. Improvements of Abeta(25-35)-induced neuritic atrophy by Kihi-to and the mechanism were investigated in cultured cortical neurons. Administration of Kihi-to for consecutive 3 days resulted in marked improvements of Abeta(25-35)-induced impairments in memory acquisition, memory retention, and object recognition memory in mice. Immunohistochemical comparisons suggested that Kihi-to attenuated neuritic, synaptic and myelin losses in the cerebral cortex, hippocampus and striatum. Kihi-to also attenuated the calpain increase in the cerebral cortex and hippocampus. When Kihi-to was added to cells 4 days after Abeta(25-35) treatment, axonal and dendritic outgrowths in cultured cortical neurons were restored as demonstrated by extended lengths of phosphorylated neurofilament-H (P-NF-H) and microtubule-associated protein (MAP)2-positive neurites. Abeta(25-35)-induced cell death in cortical culture was also markedly inhibited by Kihi-to. Since NF-H, MAP2 and myelin basic protein (MBP) are substrates of calpain, and calpain is known to be involved in Abeta-induced axonal atrophy, expression levels of calpain and calpastatin were measured. Treatment with Kihi-to inhibited the Abeta(25-35)-evoked increase in the calpain level and decrease in the

  2. Involvement of vimentin in neurite outgrowth damage induced by fipronil in SH-SY5Y cells.

    Science.gov (United States)

    Ruangjaroon, Theetat; Chokchaichamnankit, Daranee; Srisomsap, Chantragan; Svasti, Jisnuson; Paricharttanakul, N Monique

    2017-05-06

    Fipronil, a phenylpyrazole insecticide, is more selective in its potency towards insects than humans and is thus commonly used. In this study, we demonstrated that exposure to fipronil may pose a human health risk. We observed in vitro the shortening of neurite outgrowths of SH-SY5Y neuroblastoma cells upon treatment with fipronil, even at a non-cytotoxic concentration. Fipronil induced apoptosis involving caspase-6, which is an apoptotic effector highly implicated in neurodegenerative diseases. Moreover, at a concentration that did not induce apoptosis, mitochondrial dysfunction and autophagic vacuole formation were detected. Interestingly using proteomics, we identified vimentin to be dramatically expressed by SH-SY5Y cells as a response to fipronil treatment. Not only did the expression of total vimentin increase, different isoforms were observed, indicating alterations in post-translational modifications. Vimentin was localized at the neurite outgrowth, possibly to repair the damage in cellular structure. However at high concentrations of fipronil, vimentin was found in less defined fibrils, in bridge-like formation, and dense surrounding vacuoles. In all, our results indicate that vimentin plays an important role in fipronil-induced neurotoxicity in SH-SY5Y cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Controlled release of 6-aminonicotinamide from aligned, electrospun fibers alters astrocyte metabolism and dorsal root ganglia neurite outgrowth

    Science.gov (United States)

    Schaub, Nicholas J.; Gilbert, Ryan J.

    2011-08-01

    Following central nervous system (CNS) injury, activated astrocytes form a glial scar that inhibits the migration of axons ultimately leading to regeneration failure. Biomaterials developed for CNS repair can provide local delivery of therapeutics and/or guidance mechanisms to encourage cell migration into damaged regions of the brain or spinal cord. Electrospun fibers are a promising type of biomaterial for CNS injury since these fibers can direct cellular and axonal migration while slowly delivering therapy to the injury site. In this study, it was hypothesized that inclusion of an anti-metabolite, 6-aminonicotinamide (6AN), within poly-l-lactic acid electrospun fibers could attenuate astrocyte metabolic activity while still directing axonal outgrowth. Electrospinning parameters were varied to produce highly aligned electrospun fibers that contained 10% or 20% (w/w) 6AN. 6AN release from the fiber substrates occurred continuously over 2 weeks. Astrocytes placed onto drug-releasing fibers were less active than those cultured on scaffolds without 6AN. Dorsal root ganglia placed onto control and drug-releasing scaffolds were able to direct neurites along the aligned fibers. However, neurite outgrowth was stunted by fibers that contained 20% 6AN. These results show that 6AN release from aligned, electrospun fibers can decrease astrocyte activity while still directing axonal outgrowth.

  4. Mathematical Relationships between Neuron Morphology and Neurite Growth Dynamics in Drosophila melanogaster Larva Class IV Sensory Neurons

    Science.gov (United States)

    Ganguly, Sujoy; Liang, Xin; Grace, Michael; Lee, Daniel; Howard, Jonathon

    The morphology of neurons is diverse and reflects the diversity of neuronal functions, yet the principles that govern neuronal morphogenesis are unclear. In an effort to better understand neuronal morphogenesis we will be focusing on the development of the dendrites of class IV sensory neuron in Drosophila melanogaster. In particular we attempt to determine how the the total length, and the number of branches of dendrites are mathematically related to the dynamics of neurite growth and branching. By imaging class IV neurons during early embryogenesis we are able to measure the change in neurite length l (t) as a function of time v (t) = dl / dt . We found that the distribution of v (t) is well characterized by a hyperbolic secant distribution, and that the addition of new branches per unit time is well described by a Poisson process. Combining these measurements with the assumption that branching occurs with equal probability anywhere along the dendrite we were able to construct a mathematical model that provides reasonable agreement with the observed number of branches, and total length of the dendrites of the class IV sensory neuron.

  5. Major vault protein is expressed along the nucleus-neurite axis and associates with mRNAs in cortical neurons.

    Science.gov (United States)

    Paspalas, Constantinos D; Perley, Casey C; Venkitaramani, Deepa V; Goebel-Goody, Susan M; Zhang, YongFang; Kurup, Pradeep; Mattis, Joanna H; Lombroso, Paul J

    2009-07-01

    Major Vault Protein (MVP), the main constituent of the vault ribonucleoprotein particle, is highly conserved in eukaryotic cells and upregulated in a variety of tumors. Vaults have been speculated to function as cargo transporters in several cell lines, yet no work to date has characterized the protein in neurons. Here we first describe the cellular and subcellular expression of MVP in primate and rodent cerebral cortex, and in cortical neurons in vitro. In prefrontal, somatosensory and hippocampal cortices, MVP was predominantly expressed in pyramidal neurons. Immunogold labeled free and attached ribosomes, and structures reminiscent of vaults on the rough endoplasmic reticulum and the nuclear envelope. The nucleus was immunoreactive in association with nucleopores. Axons and particularly principal dendrites expressed MVP along individual microtubules, and in pre- and postsynaptic structures. Synapses were not labeled. Colocalization with microtubule-associated protein-2, tubulin, tau, and phalloidin was observed in neurites and growth cones in culture. Immunoprecipitation coupled with reverse transcription PCR showed that MVP associates with mRNAs that are known to be translated in response to synaptic activity. Taken together, our findings provide the first characterization of neuronal MVP along the nucleus-neurite axis and may offer new insights into its possible function(s) in the brain.

  6. Research Progress on the Risk Factors and Outcomes of Human Carotid Atherosclerotic Plaques.

    Science.gov (United States)

    Xiong, Xiang-Dong; Xiong, Wei-Dong; Xiong, Shang-Shen; Chen, Gui-Hai

    2017-03-20

    Atherosclerosis is an inflammatory process that results in complex lesions or plaques that protrude into the arterial lumen. Carotid atherosclerotic plaque rupture, with distal atheromatous debris embolization, causes cerebrovascular events. This review aimed to explore research progress on the risk factors and outcomes of human carotid atherosclerotic plaques, and the molecular and cellular mechanisms of human carotid atherosclerotic plaque vulnerability for therapeutic intervention. We searched the PubMed database for recently published research articles up to June 2016, with the key words of "risk factors", "outcomes", "blood components", "molecular mechanisms", "cellular mechanisms", and "human carotid atherosclerotic plaques". The articles, regarding the latest developments related to the risk factors and outcomes, atherosclerotic plaque composition, blood components, and consequences of human carotid atherosclerotic plaques, and the molecular and cellular mechanisms of human carotid atherosclerotic plaque vulnerability for therapeutic intervention, were selected. This review described the latest researches regarding the interactive effects of both traditional and novel risk factors for human carotid atherosclerotic plaques, novel insights into human carotid atherosclerotic plaque composition and blood components, and consequences of human carotid atherosclerotic plaque. Carotid plaque biology and serologic biomarkers of vulnerability can be used to predict the risk of cerebrovascular events. Furthermore, plaque composition, rather than lesion burden, seems to most predict rupture and subsequent thrombosis.

  7. Efficacy of three toothbrushes on established gingivitis and plaque.

    Science.gov (United States)

    Sowinski, Joseph; Petrone, Dolores M; Wachs, Gerald N; Chaknis, Patricia; Kemp, James; Sprosta, Al A; Devizio, William

    2008-12-01

    To evaluate the efficacy of three toothbrushes [Colgate 3600 Deep Clean (AFT version), the Colgate 3600 Deep Clean (stapled version) and the Oral B Indicator] on the removal of established gingivitis and plaque. This examiner-blind, three-treatment, parallel clinical research study assessed plaque removal via the comparison of pre-to- post-brushing and 4-week plaque removal measured by the Rustogi Modification of the Modified Navy Plaque Index. This study also assessed gingivitis using the Löe & Silness Gingival Index. Qualifying adult male and female subjects from the Northern New Jersey area reported to the study site after refraining from any oral hygiene procedures for 12 hours; and from eating, drinking, or smoking for 4 hours. Following an examination for gingivitis and plaque (pre-brushing), they were randomized into three balanced groups, each group using one of the three study toothbrushes in the order specified by a pre-determined randomization plan. Subjects were instructed to brush their teeth for 1 minute under supervision with their assigned toothbrush and a commercially-available toothpaste (Colgate Cavity Protection), after which they were once again evaluated for plaque (post-brushing). Subjects were then dismissed from the study site with the toothpaste and their assigned toothbrush to use at home twice daily for the next 4 weeks. They again reported to the study site at which time they were evaluated for plaque and gingivitis. 109 subjects complied with the protocol and completed the clinical study. For plaque removal, comparisons were made for whole mouth, at the gingival margin and at interproximal sites. The results of the study indicated that all three test toothbrushes provided statistically significantly reductions in pre- to post-brushing plaque index scores of up to 44.0%, 38.6% and 23.6% respectively, after a single toothbrushing. Relative to the Oral B Indicator toothbrush, the Colgate 360 degree Deep Clean toothbrush (AFT version) and

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

    Science.gov (United States)

    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 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.

  9. Effects of extracellular plaque components on the chlorhexidine sensitivity of strains of Streptococcus mutans and human dental plaque

    Energy Technology Data Exchange (ETDEWEB)

    Wolinsky, L.E.; Hume, W.R.

    1985-08-01

    An in vitro study was undertaken to determine the effects of sucrose-derived extracellular plaque components on the sensitivity of selected oral bacteria to chlorhexidine (CX). Cultures of Streptococcus mutans HS-6, OMZ-176, Ingbritt C, 6715-wt13, and pooled human plaque were grown in trypticase soy media with or without 1% sucrose. The sensitivity to CX of bacteria grown in each medium was determined by fixed-time exposure to CX and subsequent measurement of /sup 3/H-thymidine uptake. One-hour exposure to CX at concentrations of 10(-4) M (0.01% w/v) or greater substantially inhibited subsequent cellular division among all the S. mutans strains and human plaque samples tested. An IC50 (the CX concentration which depressed /sup 3/H-thymidine incorporation to 50% of control level) of close to 10(-4) M was noted for S. mutans strains HS-6, OMZ-176, and 6715-wt13 when grown in the presence of sucrose. The same strains grown in cultures without added sucrose showed about a ten-fold greater sensitivity to CX (IC50 close to 10(-5) M). A three-fold difference was noted for S. mutans Ingbritt C. Only a slight increase in the IC50 was noted for the plaque samples cultured in sucrose-containing media, but their threshold for depression of /sup 3/H-thymidine uptake by CX was lower than that for the sucrose-free plaque samples. The study showed that extracellular products confer some protection against CX to the bacteria examined, and provided an explanation for the disparity between clinically-recommended concentrations for plaque suppression and data on in vitro susceptibility.

  10. Neovascularization of the atherosclerotic plaque: interplay between atherosclerotic lesion, adventitia-derived microvessels and perivascular fat

    NARCIS (Netherlands)

    van Hinsbergh, Victor W. M.; Eringa, Etto C.; Daemen, Mat J. A. P.

    2015-01-01

    Neovascularization is a prominent feature in advanced human atherosclerotic plaques. This review surveys recent evidence for and remaining uncertainties regarding a role of neovascularization in atherosclerotic plaque progression. Specific emphasis is given to hypoxia, angiogenesis inhibition, and

  11. Gene expression levels of matrix metalloproteinases in human atherosclerotic plaques and evaluation of radiolabeled inhibitors as imaging agents for plaque vulnerability.

    Science.gov (United States)

    Müller, Adrienne; Krämer, Stefanie D; Meletta, Romana; Beck, Katharina; Selivanova, Svetlana V; Rancic, Zoran; Kaufmann, Philipp A; Vos, Bernhard; Meding, Jörg; Stellfeld, Timo; Heinrich, Tobias K; Bauser, Marcus; Hütter, Joachim; Dinkelborg, Ludger M; Schibli, Roger; Ametamey, Simon M

    2014-08-01

    Atherosclerotic plaque rupture is the primary cause for myocardial infarction and stroke. During plaque progression macrophages and mast cells secrete matrix-degrading proteolytic enzymes, such as matrix metalloproteinases (MMPs). We studied levels of MMPs and tissue inhibitor of metalloproteinases-3 (TIMP-3) in relation to the characteristics of carotid plaques. We evaluated in vitro two radiolabeled probes targeting active MMPs towards non-invasive imaging of rupture-prone plaques. Human carotid plaques obtained from endarterectomy were classified into stable and vulnerable by visual and histological analysis. MMP-1, MMP-2, MMP-8, MMP-9, MMP-10, MMP-12, MMP-14, TIMP-3, and CD68 levels were investigated by quantitative polymerase chain reaction. Immunohistochemistry was used to localize MMP-2 and MMP-9 with respect to CD68-expressing macrophages. Western blotting was applied to detect their active forms. A fluorine-18-labeled MMP-2/MMP-9 inhibitor and a tritiated selective MMP-9 inhibitor were evaluated by in vitro autoradiography as potential lead structures for non-invasive imaging. Gene expression levels of all MMPs and CD68 were elevated in plaques. MMP-1, MMP-9, MMP-12 and MMP-14 were significantly higher in vulnerable than stable plaques. TIMP-3 expression was highest in stable and low in vulnerable plaques. Immunohistochemistry revealed intensive staining of MMP-9 in vulnerable plaques. Western blotting confirmed presence of the active form in plaque lysates. In vitro autoradiography showed binding of both inhibitors to stable and vulnerable plaques. MMPs differed in their expression patterns among plaque phenotypes, providing possible imaging targets. The two tested MMP-2/MMP-9 and MMP-9 inhibitors may be useful to detect atherosclerotic plaques, but not the vulnerable lesions selectively. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Topical tazarotene vs. coal tar in stable plaque psoriasis

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, U.; Kaur, I.; Dogra, S.; De, D.; Kumar, B. [Postgraduate Institute of Medical Education & Research, Chandigarh (India)

    2010-07-15

    The efficacy of topical tazarotene has not previously been compared with the conventional topical treatment of crude coal tar (CCT) in stable plaque psoriasis. In this nonblinded side-to-side comparison study, patients with chronic stable plaque psoriasis, who had bilaterally symmetrical plaques on the limbs, applied 0.1% tazarotene gel on the right side and 5% CCT ointment on the left side once daily for 12 weeks followed by an 8-week treatment-free follow up period. Severity of psoriatic lesions and response to treatment was evaluated by scoring erythema, scaling and induration (ESI). Of 30 patients recruited, 27 could be assessed. In the per-protocol analysis, the mean percentage reduction in ESI score at the end of the treatment period was 74.15% {+-} 9.43 and 77.37% {+-} 10.93 with tazarotene and CCT, respectively (P {gt} 0.05). A reduction in ESI score of {gt} 75% was seen in 11 (40.74%) and 16 (59.26%) patients with tazarotene and CCT, respectively, at the end of 12 weeks. Side-effects were seen in 48.14% of patients treated with tazarotene, but in no patient treated with CCT. Tazarotene 0.1% gel has comparable clinical efficacy to CCT 5% ointment. CCT ointment remains a cost-effective therapy for plaque psoriasis.

  13. Flexural versus plaque lesions in psoriasis: an immunohistochemical differentiation.

    NARCIS (Netherlands)

    Vissers, W.H.P.M.; Roelofzen, J.H.J.; Jong, E.M.G.J. de; Erp, P.E.J. van; Kerkhof, P.C.M. van de

    2005-01-01

    Clinical presentation, therapeutic options, micro-environment and HLA-typing have been reported to be different in flexural psoriasis as compared to plaque psoriasis. We were interested in any difference concerning the pathogenesis of both conditions. By analysing T-cell subsets, NK-T cells and

  14. Does dentifrice use help to remove plaque? A systematic review

    NARCIS (Netherlands)

    Valkenburg, Cees; Slot, Dagmar E.; Bakker, Eric W. P.; van der Weijden, Fridus A.

    2016-01-01

    The aim of this systematic review was to establish the efficacy of brushing with and without a dentifrice for dental plaque removal. MEDLINE-PubMed, Cochrane-CENTRAL, EMBASE and other electronic databases were searched. The inclusion criteria were randomized controlled trials and controlled clinical

  15. Development of Tc-99m Imaging Agents for Abeta Plaques

    Energy Technology Data Exchange (ETDEWEB)

    Zhi-Ping, Zhuang; Mei-Ping Kung; Catherihne Hou; Hank F. Kung

    2008-09-26

    Development of SPECT imaging agents based on Tc-99m targeting Aβ plaques is useful for diagnosis of Alzheimer’s disease (AD). A stilbene derivative, [11C]SB-13, showing promise in detecting senile plaques present in AD patients has been reported previously1,2. Based on the 4’-amino-stilbene core structure we have added substituted groups through which a chelating group, N2S2, was conjugated. We report herein a series of Tc-99m labeled stilbene derivative conjugated with a TcO[N2S2] core. The syntheses of stilbenes containing a N2S2 chelating ligand are achieved by a scheme shown. Lipophilic 99mTc stilbene complexes were successfully prepared and purified through HPLC. Preliminary results of in vitro labeling of brain sections from transgenic mice showed very promising plaque labeling. These 99mTc stilbene derivatives are warranted for further evaluations as potential imaging agents targeting amyloid plaques.

  16. Intravascular palpography for high-risk vulnerable plaque assessment.

    NARCIS (Netherlands)

    Schaar, J.A.; Korte, C.L. de; Mastik, F.; Baldewsing, R.A.; Regar, E.; Feyter, P. de; Slager, C.J.; Steen, A.F.W. van der; Serruys, P.W.

    2003-01-01

    BACKGROUND: The composition of an atherosclerotic plaque is considered more important than the degree of stenosis. An unstable lesion may rupture and cause an acute thrombotic reaction. Most of these lesions contain a large lipid pool covered by an inflamed thin fibrous cap. The stress in the cap

  17. Cryotherapy increases features of plaque stability in atherosclerotic rabbits.

    Science.gov (United States)

    Verheye, Stefan; Roth, Lynn; De Meyer, Inge; Van Hove, Cor E; Nahon, Daniel; Santoianni, Domenic; Yianni, John; Martinet, Wim; Buchbinder, Maurice; De Meyer, Guido R Y

    2016-08-20

    In the last 10 years, cryotherapy has been investigated as a new technology to treat vascular disease. The efficiency of cryotherapy in stabilising atherosclerotic plaques has never been described. The purpose of the present study was to evaluate the effect of catheter-based cryotherapy on atherosclerotic plaque composition in a rabbit model of atherosclerosis. Twenty-four New Zealand white rabbits were fed a 0.3% cholesterol-supplemented diet for 24 weeks. At two predefined sites of the atherosclerotic thoracic aorta, catheter-based cryotherapy, applying either single-dose, double-dose cryotherapy or control inflation, was performed after randomisation. Rabbits were continued on a cholesterol-supplemented diet for one day (acute) or four weeks (chronic). One day after cryotherapy, apoptotic cell death of smooth muscle cells (SMCs) and endothelial cells (ECs) was observed, whereas macrophages were unaffected. Four weeks later, the amount of SMCs was restored, the EC layer was regenerated, and a subendothelial macrophage-free layer was formed, indicative of a more stable plaque. In addition, both the thickness and the type I collagen content of the fibrous cap were increased. The present study demonstrated that cryotherapy is feasible and appears to stabilise atherosclerotic plaques in a rabbit model.

  18. Symptomatic Plaque Form Gastric Candidiasis in a Patient with ...

    African Journals Online (AJOL)

    Upper gastrointestinal endoscopy revealed diffuse whitish candida plaque deposits over the gastric antrum with no ulceration or concomitant oesophageal involvement. She responded well to antifungal therapy with resolution of symptoms. This case demonstrates the occurrence of gastric candidiasis in CKD patient on ...

  19. Can chemical mouthwash agents achieve plaque/gingivitis control?

    NARCIS (Netherlands)

    van der Weijden, F.A.; Van der Sluijs, E.; Ciancio, S.G.; Slot, D.E.

    2015-01-01

    Key points • Oral health is important since the mouth is the gateway to the human body. Bacteria are always present in the oral cavity and when not frequently removed the dental plaque biofilm leads to the development of oral disease. • Over the past decades, the use of mouthwashes has become

  20. Plaque And Growth Characteristics Of Different Polioviruses Isolated ...

    African Journals Online (AJOL)

    Objective: To determine some virulent trait-related properties of poliovirus isolates from children with acute flaccid paralysis following vaccination with oral polio vaccine (OPV). Design: Six polioviruses earlier characterised into wild, vaccine-derived and OPV-like were studied using the plaque morphology and growth ...

  1. Vulnerable plaque detection: The role of 18-fluorine ...

    African Journals Online (AJOL)

    Shazreen Shaharuddin

    2013-07-22

    Jul 22, 2013 ... Vulnerable plaque detection: The role of 18-fluorine fluorodeoxyglucose in identifying high risk patients. Shazreen Shaharuddin a,b. , Ahmad Zaid Fattah Azman a,b. , Katiza Haida Ali c. ,. Abdul Latif Mohamad d. , Fathinul Fikri Ahmad Saad a. , Abdul Jalil Nordin a,. * a Centre for Diagnostic Nuclear Imaging ...

  2. Microbial profiling of dental plaque from mechanically ventilated patients.

    Science.gov (United States)

    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.

  3. Effect of fluoride and chlorhexidine digluconate mouthrinses on plaque biofilms

    DEFF Research Database (Denmark)

    Rabe, Per; Twetman, Svante; Kinnby, Bertil

    2015-01-01

    OBJECTIVE: To develop a model in which to investigate the architecture of plaque biofilms formed on enamel surfaces in vivo and to compare the effects of anti-microbial agents of relevance for caries on biofilm vitality. Materials and Methodology : Enamel discs mounted on healing abutments...

  4. Paraclinical Effects of Miswak Extract on Dental Plaque

    Directory of Open Access Journals (Sweden)

    Hamid Reza Poureslami

    2007-01-01

    Full Text Available Introduction: The Persian toothbrush tree or Miswak (Salvadora Persica L. has been used as a brushing stick for more than 1,300 years. Pharmacological studies indicated antibacterial and antiinflammatory activities of Miswak extract. The present study was performed to determine antibacterial effects of Miswak extract.Material and Methods: The present experimental research involved three in vitro studies including: 1 in vitro testing of the effect of Miswak extract on selected bacteria; 2 comparing the paraclinical effects of Iranian toothpaste containing Miswak extract and placebo toothpaste on dental plaque; and 3 comparing the antibacterial effect of Iranian toothpaste with Swiss toothpaste(Quail Miswak on dental plaque. The disc diffusion method was used to test bacterial sensitivity of toothpastes. Data were analyzed by paired t-test and ANOVA.Results: In the first study, Miswak extract inhibited the growth of some dental plaque bacteria. In the second study, antibacterial effect of the herbal toothpaste was significantly greater than that of the placebo (P =0.002. In the third study, four samples of dental plaque bacteria were used and there was no difference between the antibacterial effects of Swiss and Iranian herbal toothpastes (P =0.66.Conclusion: Due to antimicrobial effects of Miswak extract, its use in mouth rinses and toothpastes is highly recommended.

  5. Mast cells mediate neutrophil recruitment during atherosclerotic plaque progression

    NARCIS (Netherlands)

    Wezel, Anouk; Lagraauw, H Maxime; van der Velden, Daniël; de Jager, Saskia C A; Quax, Paul H A; Kuiper, Johan; Bot, Ilze

    AIMS: Activated mast cells have been identified in the intima and perivascular tissue of human atherosclerotic plaques. As mast cells have been described to release a number of chemokines that mediate leukocyte fluxes, we propose that activated mast cells may play a pivotal role in leukocyte

  6. Comparative Plaque Removal Efficacy of Three Manual Toothbrushes.

    Science.gov (United States)

    Ghassemi, A; Vorwerk, L; Hooper, W; Kwang, M; Naji, M; Goyal, C R; Qaqish, J

    2016-09-01

    The purpose of this study was to determine the safety and plaque-reducing effectiveness of a newly designed manual toothbrush compared to that of a leading marketed toothbrush and a reference standard manual toothbrush control. This examiner-blind, randomized, single-use study used a cross-over design. Sixty-eight qualifying male and female subjects were randomly assigned either an Arm & Hammer™ Truly Radiant™ Deep Clean manual toothbrush (TR), a Colgate® Extra Clean manual toothbrush (C), or an ADA reference standard manual toothbrush (SM) according to one of three computer-generated sequences. Following instruction in the use of their assigned brush, subjects brushed at home with a standard fluoride toothpaste twice daily for two minutes during a one-week familiarization period. At the end of this period, the subjects returned to the study site after refraining from oral hygiene for 12-16 hours and from eating and drinking for four hours. Plaque was disclosed and scored using the Rustogi Modification of the Navy Plaque Index (RMNPI). Subjects brushed under supervision with their assigned toothbrush for two minutes in a room without mirrors and apart from the dental examiner, after which plaque was disclosed and rescored. They were then given one of the alternate toothbrushes according to their assigned sequence, and the familiarization routine and evaluations were repeated until each of the subjects used each of the three brushes. Within-treatment and between-treatment whole mouth RMNPI scores and scores at each of twelve subsets of sites were analyzed using paired t-tests and appropriate ANCOVA models, respectively. Within-group analyses showed that all three toothbrushes produced statistically significant reductions from the pre-brushing baseline in whole mouth RMNPI scores (p toothbrushes produced significant supragingival plaque reductions with a single use, the Truly Radiant Deep Clean brush was significantly more effective than the Colgate Extra Clean

  7. Microflora and chemical composition of dental plaque from subjects with hereditary fructose intolerance.

    OpenAIRE

    Hoover, C I; Newbrun, E; Mettraux, G; Graf, H

    1980-01-01

    We compared the microbiological and chemical composition of dental plaque from subjects with hereditary fructose intolerance who restrict their dietary sugar intake with that of control subjects who do not. The two groups showed no significant differences in chemical composition of plaque: the mean protein, carbohydrate, calcium, magnesium, and phosphate contents were similar. Dental plaque from both groups contained similar numbers of total colony-forming units per microgram of plaque protei...

  8. Plaque characterization in ex vivo MRI evaluated by dense 3D correspondence with histology

    DEFF Research Database (Denmark)

    van Engelen, Arna; de Bruijne, Marleen; Klein, Stefan

    2011-01-01

    Automatic quantification of carotid artery plaque composition is important in the development of methods that distinguish vulnerable from stable plaques. MRI has shown to be capable of imaging different components noninvasively. We present a new plaque classification method which uses 3D....... Histological slices of human atherosclerotic plaques were manually segmented into necrotic core, fibrous tissue and calcification. Classification of these three components was voxelwise evaluated. As features the intensity, gradient magnitude and Laplacian in four MRI sequences after different degrees...

  9. Lung density

    DEFF Research Database (Denmark)

    Garnett, E S; Webber, C E; Coates, G

    1977-01-01

    The density of a defined volume of the human lung can be measured in vivo by a new noninvasive technique. A beam of gamma-rays is directed at the lung and, by measuring the scattered gamma-rays, lung density is calculated. The density in the lower lobe of the right lung in normal man during quiet...... breathing in the sitting position ranged from 0.25 to 0.37 g.cm-3. Subnormal values were found in patients with emphsema. In patients with pulmonary congestion and edema, lung density values ranged from 0.33 to 0.93 g.cm-3. The lung density measurement correlated well with the findings in chest radiographs...... but the lung density values were more sensitive indices. This was particularly evident in serial observations of individual patients....

  10. Diode-light transillumination for ophthalmic plaque localization around juxtapapillary choroidal melanomas.

    Science.gov (United States)

    Finger, P T; Iezzi, R; Esteveo, M L; Szechter, A; Rosen, R B; Berson, A

    1999-07-01

    An evaluation of plaque-mounted diode-light transillumination (DLT) for localization of episcleral plaques beneath juxtapapillary tumors. Two patients scheduled for radiotherapy for juxtapapillary melanomas were offered DLT as an additional method of ophthalmic plaque localization. Plaques were constructed by affixing 4 non-heat producing, light-emitting diodes with their apertures flush with the episcleral outer surface of the plaque's rim. Bio-implantable epoxy was used to encapsulate the electronic components. Then the plaques were loaded with 103Pd seeds. After the eye-plaques were sewn to the episclera covering the base of the intraocular tumors; the diode-lights were illuminated, viewed and recorded. Photodocumentation of the relative position of the 4 lights around tumor's base was obtained in both cases. Digital images of plaque-mounted diode retro-transillumination were obtained. No evidence of diode-light toxicity was noted. Both tumors were found to be covered by the ophthalmic plaques. Juxtapapillary tumors are often difficult or impossible to visualize with standard transillumination techniques and have been associated with poor local control rates. We have developed plaque-mounted DLT in an effort to improve ophthalmic plaque localization. Retrobulbar transillumination was viewed by indirect ophthalmoscopy and recorded with video-imaging. This technique provides unique photographic documentation of episcleral plaque localization beneath juxtapapillary tumors.

  11. Dynamics of red fluorescent dental plaque during experimental gingivitis-A cohort study

    NARCIS (Netherlands)

    van der Veen, M.H.; Volgenant, C.M.C.; Keijser, B.; ten Cate, J.M.; Crielaard, W.

    2016-01-01

    Objectives: The dynamics of red fluorescent plaque (RFP) in comparison to clinical plaque and bleeding scores were studied during an experimental gingivitis protocol in a cohort of healthy participants. Methods: Forty-one participants were monitored for RFP before (24 h plaque), during 14 days

  12. How radiation influences atherosclerotic plaque development: a biophysical approach in ApoE⁻/⁻ mice.

    Science.gov (United States)

    Kloosterman, Astrid; Dillen, Teun van; Bijwaard, Harmen; Heeneman, Sylvia; Hoving, Saske; Stewart, Fiona A; Dekkers, Fieke

    2017-11-01

    Atherosclerosis is the development of lipid-laden plaques in arteries and is nowadays considered as an inflammatory disease. It has been shown that high doses of ionizing radiation, as used in radiotherapy, can increase the risk of development or progression of atherosclerosis. To elucidate the effects of radiation on atherosclerosis, we propose a mathematical model to describe radiation-promoted plaque development. This model distinguishes itself from other models by combining plaque initiation and plaque growth, and by incorporating information from biological experiments. It is based on two consecutive processes: a probabilistic dose-dependent plaque initiation process, followed by deterministic plaque growth. As a proof of principle, experimental plaque size data from carotid arteries from irradiated ApoE[Formula: see text] mice was used to illustrate how this model can provide insight into the underlying biological processes. This analysis supports the promoting role for radiation in plaque initiation, but the model can easily be extended to include dose-related effects on plaque growth if available experimental data would point in that direction. Moreover, the model could assist in designing future biological experiments on this research topic. Additional biological data such as plaque size data from chronically-irradiated mice or experimental data sets with a larger variety in biological parameters can help to further unravel the influence of radiation on plaque development. To the authors' knowledge, this is the first biophysical model that combines probabilistic and mechanistic modeling which uses experimental data to investigate the influence of radiation on plaque development.

  13. How radiation influences atherosclerotic plaque development. A biophysical approach in ApoE{sup -/-} mice

    Energy Technology Data Exchange (ETDEWEB)

    Kloosterman, Astrid; Dillen, Teun van; Dekkers, Fieke [National Institute for Public Health and the Environment (RIVM), Centre for Environmental Safety and Security, Bilthoven (Netherlands); Bijwaard, Harmen [National Institute for Public Health and the Environment (RIVM), Centre for Environmental Safety and Security, Bilthoven (Netherlands); Inholland University of Applied Sciences, Medical Technology Research Group, Haarlem (Netherlands); Heeneman, Sylvia [Maastricht University Medical Center, Experimental Vascular Pathology group, Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht (Netherlands); Hoving, Saske; Stewart, Fiona A. [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Division of Biological Stress Response (H3), Amsterdam (Netherlands)

    2017-11-15

    Atherosclerosis is the development of lipid-laden plaques in arteries and is nowadays considered as an inflammatory disease. It has been shown that high doses of ionizing radiation, as used in radiotherapy, can increase the risk of development or progression of atherosclerosis. To elucidate the effects of radiation on atherosclerosis, we propose a mathematical model to describe radiation-promoted plaque development. This model distinguishes itself from other models by combining plaque initiation and plaque growth, and by incorporating information from biological experiments. It is based on two consecutive processes: a probabilistic dose-dependent plaque initiation process, followed by deterministic plaque growth. As a proof of principle, experimental plaque size data from carotid arteries from irradiated ApoE{sup -/-} mice was used to illustrate how this model can provide insight into the underlying biological processes. This analysis supports the promoting role for radiation in plaque initiation, but the model can easily be extended to include dose-related effects on plaque growth if available experimental data would point in that direction. Moreover, the model could assist in designing future biological experiments on this research topic. Additional biological data such as plaque size data from chronically-irradiated mice or experimental data sets with a larger variety in biological parameters can help to further unravel the influence of radiation on plaque development. To the authors' knowledge, this is the first biophysical model that combines probabilistic and mechanistic modeling which uses experimental data to investigate the influence of radiation on plaque development. (orig.)

  14. Ultrasonic mirror image from ruthenium plaque facilitates calculation of uveal melanoma treatment dose

    DEFF Research Database (Denmark)

    Espensen, Charlotte Alfast; Jensen, Peter Koch; Fog, Lotte Stubkjær

    2017-01-01

    to illustrate the effects on radiation dose to apex of the tumour when the dose depth was incorrectly determined. Doses to apex of the tumour were determined using Plaque Simulator. Results The intraobserver variation in dose depth measurement with plaque was significantly lower than for measures without plaque...

  15. Stable Size Distribution of Amyloid Plaques Over the Course of Alzheimer Disease

    Science.gov (United States)

    Serrano-Pozo, Alberto; Mielke, Matthew L.; Muzitansky, Alona; Gómez-Isla, Teresa; Growdon, John H.; Bacskai, Brian J.; Betensky, Rebecca A.; Frosch, Matthew P.; Hyman, Bradley T.

    2012-01-01

    Amyloid-β plaques are a key pathological feature of Alzheimer disease (AD), but whether plaque sizes increase or stabilize over the course of AD is unknown. We measured the size distribution of total immunoreactive (10D5-positive) and dense-core (Thioflavine-S-positive) plaques in the temporal neocortex of a large group of AD and plaque-bearing age-matched non-demented subjects to test the hypothesis that amyloid plaques continue to grow along with the progression of the disease. The size of amyloid-β (10D5)-positive plaques did not differ between groups whereas dense-core plaques from the AD group were slightly larger than those in the non-demented group (~25%–30%, p = 0.01). Within the AD group, dense-core plaque size did not independently correlate with duration of clinical disease (from 4 to 21 years, p = 0.68), whereas 10D5-positive plaque size correlated negatively with disease duration (p = 0.01). By contrast, an earlier age of symptom onset strongly predicted a larger postmortem plaque size; this effect was independent of disease duration and the presence of the APOEε4 allele (p = 0.0001). We conclude that plaques vary in size among patients, with larger size distributions correlating with an earlier age of onset, but plaques do not substantially increase in size over the clinical course of the disease. PMID:22805771

  16. Intravascular Ultrasound Elastography: A Clinician's Tool for Assessing Vulnerability and Material Composition of Plaques.

    NARCIS (Netherlands)

    Baldewsing, R.A.; Schaar, J.A.; Korte, C.L. de; Mastik, F.; Serruys, P.W.; Steen, A.F.W. van der

    2005-01-01

    The material composition and morphology of the atherosclerotic plaque components are considered to be more important determinants of acute coronary ischemic syndromes than the degree of stenosis. When a vulnerable plaque ruptures it causes an acute thrombotic reaction. Rupture prone plaques contain

  17. Lectin Pathway of Complement Activation Is Associated with Vulnerability of Atherosclerotic Plaques

    DEFF Research Database (Denmark)

    Fumagalli, Stefano; Perego, Carlo; Zangari, Rosalia

    2017-01-01

    to plaque vulnerability. Ficolins and MBL were found both in plaques' necrotic core and tunica media. Patients with vulnerable plaques showed decreased plasma levels and intraplaque deposition of ficolin-2. Symptomatic patients experiencing a transient ischemic attack had lower plasma levels of ficolin-1...

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

    NARCIS (Netherlands)

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

    2016-01-01

    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

  19. 21 CFR 872.5580 - Oral rinse to reduce the adhesion of dental plaque.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Oral rinse to reduce the adhesion of dental plaque... adhesion of dental plaque. (a) Identification. The device is assigned the generic name oral rinse to reduce the adhesion of dental plaque and is identified as a device intended to reduce the presence of...

  20. 76 FR 66307 - Scientific Information Request on Phototherapy for Treatment of Chronic Plaque Psoriasis

    Science.gov (United States)

    2011-10-26

    ... for Treatment of Chronic Plaque Psoriasis AGENCY: Agency for Healthcare Research and Quality (AHRQ... Phototherapy medical devices for treatment of chronic plaque psoriasis. Scientific information is being... Phototherapy for Treatment of Chronic Plaque Psoriasis, which is currently being conducted by the Evidence...

  1. Spiral computed tomographic imaging related to computerized ultrasonographic images of carotid plaque morphology and histology

    DEFF Research Database (Denmark)

    Grønholdt, Marie-Louise; Wagner, A; Wiebe, B M

    2001-01-01

    Echolucency of carotid atherosclerotic plaques, as evaluated by computerized B-mode ultrasonographic images, has been associated with an increased incidence of brain infarcts on cerebral computed tomographic scans. We tested the hypotheses that characterization of carotid plaques on spiral computed...... tomographic images correlates with that on computerized B-mode ultrasonographic images and that spiral computed tomographic imaging predicts the histomorphometric plaque content....

  2. Adjunctive dental therapy via tooth plaque reduction and gingivitis treatment by blue light-emitting diodes tooth brushing.

    Science.gov (United States)

    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.

  3. Adjunctive dental therapy via tooth plaque reduction and gingivitis treatment by blue light-emitting diodes tooth brushing

    Science.gov (United States)

    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.

  4. The unstable plaque: a diagnostic challenge in cardiology; Diagnostische Herausforderung in der Kardiologie: Die instabile arteriosklerotische Plaque

    Energy Technology Data Exchange (ETDEWEB)

    Levkau, B. [Inst. fuer Pathophysiologie, Universitaetsklinikum Essen (Germany); Schaefers, M. [Klinik und Poliklinik fuer Nuklearmedizin, Universitaetsklinikum Muenster (Germany)

    2004-09-01

    Atherosclerotic plaque rupture still accounts for one third of all deaths worldwide and constitutes a major source of disability and health care costs. Dysregulation of MMPs in the atherosclerotic lesion may result in mechanical destabilization and rupture of the atherosclerotic plaque, potentially leading to thrombosis and vessel occlusion with life-threatening clinical complications. Therefore, identifying individual patients at high risk of plaque rupture is an important challenge in clinical medicine. We have used the broad-spectrum MMP inhibitor CGS 27023A to develop the radioligand [{sup 123}I]I-HO-CGS 27023A for in vivo imaging of MMP activity. Using this radioligand, we were able to specifically image MMP activity by scintigraphy in vivo in the MMP-rich vascular lesions that develop after carotid artery ligation and cholesterol-rich diet in apolipoprotein E-deficient mice. Thus, imaging of MMP activity in vivo is feasible using radiolabelled MMP inhibitors. In combination with the high-resolution morphological imaging techniques such as MRI and CT, the molecular imaging of individual disease parameters such as MMP activity in lesions of atherosclerosis may help design approaches for the prediction and prevention of coronary events due to plaque rupture of an individual lesion in an individual patient. (orig.)

  5. Active components from Siberian ginseng (Eleutherococcus senticosus) for protection of amyloid β(25-35)-induced neuritic atrophy in cultured rat cortical neurons.

    Science.gov (United States)

    Bai, Yanjing; Tohda, Chihiro; Zhu, Shu; Hattori, Masao; Komatsu, Katsuko

    2011-07-01

    Not only neuronal death but also neuritic atrophy and synaptic loss underlie the pathogenesis of Alzheimer's disease as direct causes of the memory deficit. Extracts of Siberian ginseng (the rhizome of Eleutherococcus senticosus) were shown to have protective effects on the regeneration of neurites and the reconstruction of synapses in rat cultured cortical neurons damaged by amyloid β (Aβ)(25-35), and eleutheroside B was one of the active constituents. In this study, a comprehensive evaluation of constituents was conducted to explore active components from Siberian ginseng which can protect against neuritic atrophy induced by Aβ(25-35) in cultured rat cortical neurons. The ethyl acetate, n-butanol and water fractions from the methanol extract of Siberian ginseng showed protective effects against Aβ-induced neuritic atrophy. Twelve compounds were isolated from the active fractions and identified. Among them, eleutheroside B, eleutheroside E and isofraxidin showed obvious protective effects against Aβ(25-35)-induced atrophies of axons and dendrites at 1 and 10 μM.

  6. Effect of Testosterone on Neuronal Morphology and Neuritic Growth of Fetal Lamb Hypothalamus-Preoptic Area and Cerebral Cortex in Primary Culture.

    Directory of Open Access Journals (Sweden)

    Radhika C Reddy

    Full Text Available Testosterone plays an essential role in sexual differentiation of the male sheep brain. The ovine sexually dimorphic nucleus (oSDN, is 2 to 3 times larger in males than in females, and this sex difference is under the control of testosterone. The effect of testosterone on oSDN volume may result from enhanced expansion of soma areas and/or dendritic fields. To test this hypothesis, cells derived from the hypothalamus-preoptic area (HPOA and cerebral cortex (CTX of lamb fetuses were grown in primary culture to examine the direct morphological effects of testosterone on these cellular components. We found that within two days of plating, neurons derived from both the HPOA and CTX extend neuritic processes and express androgen receptors and aromatase immunoreactivity. Both treated and control neurites continue to grow and branch with increasing time in culture. Treatment with testosterone (10 nM for 3 days significantly (P < 0.05 increased both total neurite outgrowth (35% and soma size (8% in the HPOA and outgrowth (21% and number of branch points (33% in the CTX. These findings indicate that testosterone-induced somal enlargement and neurite outgrowth in fetal lamb neurons may contribute to the development of a fully masculine sheep brain.

  7. Inhibition of mTOR by Rapamycin Results in Auditory Hair Cell Damage and Decreased Spiral Ganglion Neuron Outgrowth and Neurite Formation In Vitro

    Directory of Open Access Journals (Sweden)

    Katharina Leitmeyer

    2015-01-01

    Full Text Available Rapamycin is an antifungal agent with immunosuppressive properties. Rapamycin inhibits the mammalian target of rapamycin (mTOR by blocking the mTOR complex 1 (mTORC1. mTOR is an atypical serine/threonine protein kinase, which controls cell growth, cell proliferation, and cell metabolism. However, less is known about the mTOR pathway in the inner ear. First, we evaluated whether or not the two mTOR complexes (mTORC1 and mTORC2, resp. are present in the mammalian cochlea. Next, tissue explants of 5-day-old rats were treated with increasing concentrations of rapamycin to explore the effects of rapamycin on auditory hair cells and spiral ganglion neurons. Auditory hair cell survival, spiral ganglion neuron number, length of neurites, and neuronal survival were analyzed in vitro. Our data indicates that both mTOR complexes are expressed in the mammalian cochlea. We observed that inhibition of mTOR by rapamycin results in a dose dependent damage of auditory hair cells. Moreover, spiral ganglion neurite number and length of neurites were significantly decreased in all concentrations used compared to control in a dose dependent manner. Our data indicate that the mTOR may play a role in the survival of hair cells and modulates spiral ganglion neuronal outgrowth and neurite formation.

  8. Optimisation of a 96-well electroporation assay for postnatal rat CNS neurons suitable for cost-effective medium-throughput screening of genes that promote neurite outgrowth

    Directory of Open Access Journals (Sweden)

    Thomas eHutson

    2011-12-01

    Full Text Available Following an injury, central nervous system (CNS neurons show a very limited regenerative response which results in their failure to successfully form functional connections with their original target. This is due in part to the reduced intrinsic growth state of CNS neurons, which is characterised by their failure to express key regeneration-associated genes (RAGs and by the presence of growth inhibitory molecules in CNS environment that form a molecular and physical barrier to regeneration. Here we have optimised a 96-well electroporation and neurite outgrowth assay for postnatal rat cerebellar granule neurons cultured upon an inhibitory cellular substrate expressing myelin-associated glycoprotein or a mixture of growth-inhibitory chondroitin sulphate proteoglycans. Optimal electroporation parameters resulted in 25% transfection efficiency and 50% viability for postnatal rat cerebellar granule neurons (CGNs. The neurite outgrowth of transduced neurons was quantitatively measured using a semi-automated image capture and analysis system. The neurite outgrowth was significantly reduced by the inhibitory substrates which we demonstrated could be partially reversed using a Rho Kinase inhibitor. We are now using this assay to screen large sets of RAGs for their ability to increase neurite outgrowth on a variety of growth inhibitory and permissive substrates.

  9. Recreational drugs, 3,4-Methylenedioxymethamphetamine(MDMA), 3,4-methylenedioxyamphetamine (MDA) and diphenylprolinol, inhibit neurite outgrowth in PC12 cells.

    Science.gov (United States)

    Kaizaki, Asuka; Tanaka, Sachiko; Tsujikawa, Kenji; Numazawa, Satoshi; Yoshida, Takemi

    2010-06-01

    3,4-Methylenedioxymethamphetamine (MDMA) is widely abused as a psychoactive recreational drug. It is well known that MDMA induces neurotoxic damage of serotonergic nerve endings. Although drug abuse is increasing among youths, it is unclear whether recreational drugs affect the development of nerve growth. Thus, the present study examined the effect of recreational drugs, such as MDMA, 3,4-methylenedioxyamphetamine (MDA) and diphenylprolinol, a novel recreational drug with a similar chemical structure as that of psychoactive agent pipradrol, on nerve growth factor (NGF)-induced neurite outgrowth. These recreational drugs induced a dose-dependent cell death in PC12 cells. The IC(50) values of MDMA, MDA, R-diphenylprolinol and S-diphenylprolinol were 4.11 mM, 2.75 mM, 1.00 mM and 0.77 mM, respectively, at 24 hr. To examine the effects of these recreational drugs on NGF-induced neurite outgrowth, PC12 cells were treated with NGF together with MDMA, MDA, S-diphenylprolinol or R-diphenylprolinol at low toxic concentrations. The recreational drugs significantly suppressed neurite outgrowth of PC12 cells induced by NGF. The results suggest that these psychoactive recreational drugs may inhibit neurite growth and thus be implicated in their elicited neurotoxicity.

  10. Extracellular Nm23H1 stimulates neurite outgrowth from dorsal root ganglia neurons in vitro independently of nerve growth factor supplementation or its nucleoside diphosphate kinase activity.

    Science.gov (United States)

    Wright, K T; Seabright, R; Logan, A; Lilly, A J; Khanim, F; Bunce, C M; Johnson, W E B

    2010-07-16

    The nucleoside diphosphate (NDP) kinase, Nm23H1, is a highly expressed during neuronal development, whilst induced over-expression in neuronal cells results in increased neurite outgrowth. Extracellular Nm23H1 affects the survival, proliferation and differentiation of non-neuronal cells. Therefore, this study has examined whether extracellular Nm23H1 regulates nerve growth. We have immobilised recombinant Nm23H1 proteins to defined locations of culture plates, which were then seeded with explants of embryonic chick dorsal root ganglia (DRG) or dissociated adult rat DRG neurons. The substratum-bound extracellular Nm23H1 was stimulatory for neurite outgrowth from chick DRG explants in a concentration-dependent manner. On high concentrations of Nm23H1, chick DRG neurite outgrowth was extensive and effectively limited to the location of the Nm23H1, i.e. neuronal growth cones turned away from adjacent collagen-coated substrata. Nm23H1-coated substrata also significantly enhanced rat DRG neuronal cell adhesion and neurite outgrowth in comparison to collagen-coated substrata. These effects were independent of NGF supplementation. Recombinant Nm23H1 (H118F), which does not possess NDP kinase activity, exhibited the same activity as the wild-type protein. Hence, a novel neuro-stimulatory activity for extracellular Nm23H1 has been identified in vitro, which may function in developing neuronal systems. Copyright 2010 Elsevier Inc. All rights reserved.

  11. Minocycline Promotes Neurite Outgrowth of PC12 Cells Exposed to Oxygen-Glucose Deprivation and Reoxygenation Through Regulation of MLCP/MLC Signaling Pathways.

    Science.gov (United States)

    Tao, Tao; Feng, Jin-Zhou; Xu, Guang-Hui; Fu, Jie; Li, Xiao-Gang; Qin, Xin-Yue

    2017-04-01

    Minocycline, a semi-synthetic second-generation derivative of tetracycline, has been reported to exert neuroprotective effects both in animal models and in clinic trials of neurological diseases. In the present study, we first investigated the protective effects of minocycline on oxygen-glucose deprivation and reoxygenation-induced impairment of neurite outgrowth and its potential mechanism in the neuronal cell line, PC12 cells. We found that minocycline significantly increased cell viability, promoted neurite outgrowth and enhanced the expression of growth-associated protein-43 (GAP-43) in PC12 cells exposed to oxygen-glucose deprivation/reoxygenation injury. In addition, immunoblots revealed that minocycline reversed the overexpression of phosphorylated myosin light chain (MLC) and the suppression of activated extracellular signal-regulated kinase 1/2 (ERK1/2) caused by oxygen-glucose deprivation/reoxygenation injury. Moreover, the minocycline-induced neurite outgrowth was significantly blocked by Calyculin A (1 nM), an inhibitor of myosin light chain phosphatase (MLCP), but not by an ERK1/2 inhibitor (U0126; 10 μM). These findings suggested that minocycline activated the MLCP/MLC signaling pathway in PC12 cells after oxygen-glucose deprivation/reoxygenation injury, which resulted in the promotion of neurite outgrowth.

  12. Intensive lipid lowering therapy with titrated rosuvastatin yields greater atherosclerotic aortic plaque regression: Serial magnetic resonance imaging observations from RAPID study.

    Science.gov (United States)

    Yogo, Makiko; Sasaki, Makoto; Ayaori, Makoto; Kihara, Teruyoshi; Sato, Hiroki; Takiguchi, Shunichi; Uto-Kondo, Harumi; Yakushiji, Emi; Nakaya, Kazuhiro; Komatsu, Tomohiro; Momiyama, Yukihiko; Nagata, Masayoshi; Mochio, Soichiro; Iguchi, Yasuyuki; Ikewaki, Katsunori

    2014-01-01

    Although previous randomized clinical trials established a basis for lipid guidelines worldwide, they employed fixed doses of statins throughout trials (fire-and-forget approach). In the real clinical setting, however, statin doses are titrated to achieve target low-density lipoprotein cholesterol (LDL-C) levels (treat-to-target approach). The major objective was to investigate whether intensive lipid-lowering therapy using the treat-to-target approach yielded greater regression of aortic plaques. We therefore performed a prospective, randomized trial comparing the effects of standard (achieve LDL-C levels recommended by the Japanese guidelines) and intensive (achieve 30% lower LDL-C levels than standard) rosuvastatin therapy for 1 year in 60 hypercholesterolemic patients with a primary endpoint of aortic atherosclerotic plaques evaluated by non-invasive magnetic resonance imaging (MRI). Average doses were 2.9 ± 3.1 and 6.5 ± 5.1 mg/day for standard (n = 29) and intensive therapy group (n = 31), respectively. Although both therapies significantly reduced LDL-C and high-sensitivity C-reactive protein (hsCRP) levels, LDL-C reduction was significantly greater in the intensive group (-46 vs. -34%). MRI study showed that thoracic aortic plaques were significantly regressed in both groups, with greater regression of thoracic plaque in the intensive group (-9.1 vs. -3.2%, p = 0.01). Multivariate analyses revealed that thoracic plaque regression was significantly correlated with hsCRP reduction, but not with changes in serum lipids, endothelial function, or doses of rosuvastatin. Intensive statin therapy with titration targeting lower LDL-C levels resulted in greater thoracic aortic plaque regression compared to standard therapy, which was correlated with hsCRP reduction, suggesting that intensive statin therapy could provide better clinical outcomes. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  13. 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.

    Science.gov (United States)

    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.

  14. Potentiation of nerve growth factor-induced neurite outgrowth by fluvoxamine: role of sigma-1 receptors, IP3 receptors and cellular signaling pathways.

    Directory of Open Access Journals (Sweden)

    Tomoko Nishimura

    Full Text Available BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs have been widely used and are a major therapeutic advance in psychopharmacology. However, their pharmacology is quite heterogeneous. The SSRI fluvoxamine, with sigma-1 receptor agonism, is shown to potentiate nerve-growth factor (NGF-induced neurite outgrowth in PC 12 cells. However, the precise cellular and molecular mechanisms underlying potentiation by fluvoxamine are not fully understood. In this study, we examined the roles of cellular signaling pathways in the potentiation of NGF-induced neurite outgrowth by fluvoxamine and sigma-1 receptor agonists. METHODS AND FINDINGS: The effects of three SSRIs (fluvoxamine, sertraline, paroxetine and three sigma-1 receptor agonists (SA4503, 4-phenyl-1-(4-phenylbutyl piperidine (PPBP, and dehydroepiandrosterone (DHEA-sulfate on NGF-induced neurite outgrowth in PC12 cells were examined. Also examined were the effects of the sigma-1 receptor antagonist NE-100, inositol 1,4,5-triphosphate (IP(3 receptor antagonist, and specific inhibitors of signaling pathways in the potentiation of NGF-induced neurite outgrowth by selective sigma-1 receptor agonist SA4503. Fluvoxamine (but not sertraline or paroxetine and the sigma-1 receptor agonists SA4503, PPBP, and DHEA-sulfate significantly potentiated NGF-induced neurite outgrowth in PC12 cells in a concentration-dependent manner. The potentiation by fluvoxamine and the three sigma-1 receptor agonists was blocked by co-administration of the selective sigma-1 receptor antagonist NE-100, suggesting that sigma-1 receptors play a role in blocking the enhancement of NGF-induced neurite outgrowth. Moreover, the potentiation by SA4503 was blocked by co-administration of the IP(3 receptor antagonist xestospongin C. In addition, the specific inhibitors of phospholipase C (PLC-gamma, phosphatidylinositol 3-kinase (PI3K, p38MAPK, c-Jun N-terminal kinase (JNK, and the Ras/Raf/mitogen-activated protein kinase (MAPK

  15. Quantification of the uncertainty in coronary CTA plaque measurements using dynamic cardiac phantom and 3D-printed plaque models

    Science.gov (United States)

    Richards, Taylor; Sturgeon, Gregory M.; Ramirez-Giraldo, Juan Carlos; Rubin, Geoffrey; Segars, Paul; Samei, Ehsan

    2017-03-01

    The purpose of this study was to quantify the accuracy of coronary computed tomography angiography (CTA) stenosis measurements using newly developed physical coronary plaque models attached to a base dynamic cardiac phantom (Shelley Medical DHP-01). Coronary plaque models (5 mm diameter, 50% stenosis, and 32 mm long) were designed and 3D-printed with tissue equivalent materials (calcified plaque with iodine enhanced lumen). Realistic cardiac motion was achieved by fitting known cardiac motion vectors to left ventricle volume-time curves to create synchronized heart motion profiles executed by the base cardiac phantom. Realistic coronary CTA acquisition was accomplished by synthesizing corresponding ECG waveforms for gating and reconstruction purposes. All scans were acquired using a retrospective gating technique on a dual-source CT system (Siemens SOMATOM FLASH) with 75ms temporal resolution. Multi-planar reformatted images were reconstructed along vessel centerlines and the enhanced lumens were manually segmented by 5 independent operators. On average, the stenosis measurement accuracy was 0.9% positive bias for the motion free condition (0 bpm). The measurement accuracy monotonically decreased to 18.5% negative bias at 90 bpm. Contrast-tonoise (CNR), vessel circularity, and segmentation conformity also decreased monotonically with increasing heart rate. These results demonstrate successful implementation of the base cardiac phantom with 3D-printed coronary plaque models, adjustable motion profiles, and coordinated ECG waveforms. They further show the utility of the model to ascertain metrics of coronary CT accuracy and image quality under a variety of plaque, motion, and acquisition conditions.

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

    Science.gov (United States)

    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.

  17. Minimum inhibitory concentration of the plant extracts′ combinations against dental caries and plaque microorganisms: An in vitro study

    Directory of Open Access Journals (Sweden)

    B R Chandra Shekar

    2016-01-01

    Full Text Available Introduction: Oral health status has witnessed marked advances in many industrialized countries. However, dental caries is consistently increasing in developing countries, and periodontal diseases are among most common afflictions to humankind. Approach best suited for developing countries is to focus on the prevention with innovative strategies. Hence, evolution of novel, innovative strategies to prevent dental caries and periodontal diseases is need of hour. Objective: To determine minimum inhibitory concentration (MIC of combinations of Acacia nilotica, Murraya koenigii L. Sprengel, Eucalyptus hybrid, and Psidium guajava against dental caries and plaque microorganisms and to qualitatively identify various phytochemical constituents in individual plant extracts and their quadruple combinations. Materials and Methods: MIC of the combinations of A. nilotica, M. koenigii L. Sprengel, Eucalyptus hybrid, and P. guajava on Streptococcus mutans, Lactobacillus acidophilus (dental caries bacteria, Streptococcus sanguis, Streptococcus salivarius (primary plaque colonizers, Fusobacterium nucleatum (secondary plaque colonizer, and Porphyromonas gingivalis (tertiary plaque colonizer was determined using broth dilution method. Series of dilutions of quadruple combinations ranging from 0.05% to 1.5% were prepared. 100 μL of each serial dilution of quadruple combinations was added to each tube containing bacterial culture. The optical density was noted after incubation in each tube to estimate the MIC for each bacterium. Results: MIC of the polyherbal combinations on S. mutans, S. sanguis, S. salivarius, L. acidophilus, F. nucleatum, and P. gingivalis was found to be 0.25%, 0.05%, 0.05%, 0.1%, 0.25%, and 0.25%, respectively. Conclusion: The quadruple combinations of these four plant extracts could be considered in the evolution of an indigenous polyherbal mouth rinse as the formulation inhibited all the bacteria tested in the present study at low

  18. Site-based plaque removal efficacy of four branded toothbrushes and the effect of dental floss in interproximal plaque removal: a randomized examiner-blind controlled study.

    Science.gov (United States)

    Ashwath, Balachandran; Vijayalakshmi, Rajaraman; Arun, Dayanathi; Kumar, Vasanth

    2014-01-01

    The aim of this study was to evaluate the sitelevel plaque removal efficacy of four commercially available toothbrushes. The adjunctive benefit of dental floss on interproximal plaque removal was also evaluated. This study was designed as a randomized examiner- blinded clinical study involving 60 subjects. The subjects were randomly divided into four groups of 15 participants each, and a particular branded toothbrush was allotted for each group. Brushing technique, toothpaste, and brushing time were standardized for all the subjects. The Turesky- Gilmore-Glickman modification of Quigley-Hein plaque index was used to evaluate plaque scores at baseline, and 1, 2, 3, and 4 weeks by one blinded examiner. After 2 weeks, the subjects were provided with dental floss to be used in conjunction with the toothbrush. Buccal, lingual, and interproximal plaque reduction percentages were computed and analyzed for statistical significance. The four toothbrushes showed similar plaque removal scores at the three sites, with no statistical significance (P > .05). The interproximal plaque removal scores of the four toothbrushes were the least at 2 weeks (25%) when compared with buccal (65%) and lingual (60%) percentage scores. The addition of dental floss significantly increased the interproximal plaque removal scores, with 4-week scores revealing 70% removal. These data revealed the lack of significance between the four toothbrushes studied, which is in line with previous studies. The addition of dental floss had a significant effect on the interproximal plaque removal, which could be crucial in the maintenance of gingival health.

  19. Peripheral nerve regeneration and NGF-dependent neurite outgrowth of adult sensory neurons converge on STAT3 phosphorylation downstream of neuropoietic cytokine receptor gp130.

    Science.gov (United States)

    Quarta, Serena; Baeumer, Bastian E; Scherbakov, Nadja; Andratsch, Manfred; Rose-John, Stefan; Dechant, Georg; Bandtlow, Christine E; Kress, Michaela

    2014-09-24

    After nerve injury, adult sensory neurons can regenerate peripheral axons and reconnect with their target tissue. Initiation of outgrowth, as well as elongation of neurites over long distances, depends on the signaling of receptors for neurotrophic growth factors. Here, we investigated the importance of gp130, the signaling subunit of neuropoietic cytokine receptors in peripheral nerve regeneration. After sciatic nerve crush, functional recovery in vivo was retarded in SNS-gp130(-/-) mice, which specifically lack gp130 in sensory neurons. Correspondingly, a significantly reduced number of free nerve endings was detected in glabrous skin from SNS-gp130(-/-) compared with control mice after nerve crush. Neurite outgrowth and STAT3 activation in vitro were severely reduced in cultures in gp130-deficient cultured neurons. Surprisingly, in neurons obtained from SNS-gp130(-/-) mice the increase in neurite length was reduced not only in response to neuropoietic cytokine ligands of gp130 but also to nerve growth factor (NGF), which does not bind to gp130-containing receptors. Neurite outgrowth in the absence of neurotrophic factors was partially rescued in gp130-deficient neurons by leptin, which activates STAT3 downstream of leptic receptor and independent of gp130. The neurite outgrowth response of gp130-deficient neurons to NGF was fully restored in the presence of leptin. Based on these findings, gp130 signaling via STAT3 activation is suggested not only to be an important regulator of peripheral nerve regeneration in vitro and in vivo, but as determining factor for the growth promoting action of NGF in adult sensory neurons. Copyright © 2014 the authors 0270-6474/14/3413222-12$15.00/0.

  20. Co-administration of ciliary neurotrophic factor with its soluble receptor protects against neuronal death and enhances neurite outgrowth.

    Science.gov (United States)

    Ozog, Mark A; Modha, Geetanjalee; Church, John; Reilly, Rayne; Naus, Christian C

    2008-03-07

    Attempts to promote neuronal survival and repair with ciliary neurotrophic factor (CNTF) have met with limited success. The variability of results obtained with CNTF may, in part, reflect the fact that some of the biological actions of the cytokine are mediated by a complex formed between CNTF and its specific receptor, CNTFRalpha, which exists in both membrane-bound and soluble forms. In this study, we compared the actions of CNTF alone and CNTF complexed with soluble CNTFRalpha (hereafter termed "Complex") on neuronal survival and growth. Although CNTF alone produced limited effects, Complex protected against glutamate-mediated excitotoxicity via gap junction-dependent and -independent mechanisms. Further examination revealed that only Complex promoted neurite outgrowth. Differential gene expression analysis revealed that, compared with CNTF alone, Complex differentially regulates several neuroprotective and neurotrophic genes. Collectively, these findings indicate that CNTF exerts more robust effects on neuronal survival and growth when applied in combination with its soluble receptor.

  1. Estimation of Plaque Contents With Multi-Angle 3D Compound Imaging

    DEFF Research Database (Denmark)

    Wilhjelm, Jens E.; Grønholdt, Marie Louise; Rasmussen, Steen Tofthøj

    1996-01-01

    This investigation exploits the potential of using multiple insonification angles in characterizing plaques in the carotid artery. Specifically, previous work has shown that certain plaque materials such as lipid exhibit a low degree of angle-dependence in the received echo signal while the signal...... to lateral resolution size (1.4 mm @ -3 dB) to obtain an omnidirectional range cell. After scanning, the plaques underwent histological analysis in order to estimate the amount of calcification, fibrous tissues, lipid, blood and thrombus. So far, 13 plaques surgically removed during carotid endarterectomy...... and the content of fibrous tissues. The preliminary results indicate that the method has good potential for characterization of plaque....

  2. Induction of Dendritic Cell-Mediated Activation of T Cells From Atherosclerotic Plaques by Human Heat Shock Protein 60.

    Science.gov (United States)

    Rahman, Mizanur; Steuer, Johnny; Gillgren, Peter; Hayderi, Assim; Liu, Anquan; Frostegård, Johan

    2017-11-18

    Atherosclerosis is characterized by the presence of activated immune-competent cells including dendritic cells (DCs) and T cells, dead cells, and oxidized low-density lipoprotein. HSP60 (Heat shock protein 60) has been implicated in atherosclerosis. A plasma protein, Annexin A5, has atheroprotective properties. Human DCs differentiated from peripheral blood monocytes were treated with human HSP60 or HSP90 and autologous T cells were cocultured with these pretreated DCs (mDCs). HSP60 induced mDCs and T-cell activation as determined by FACScan (Fluorescence associated cell scan), gene-activation, and cytokine production. HSP60-induced T-cell activation was partly major histocompatibility complex class II-dependent. T cells exposed to HSP60-treated mDCs produced interferon-γ, interleukin-17, but not transforming growth factor-β. HSP60 did not promote expression of Toll-like receptors 2 or 4. HSP90 promoted mDCs maturation but had no effect on T-cell activation. Annexin A5 inhibited HSP60-proinflammatory Th1/Th17 effects on mDCs and T cells, and partly bound HSP60. Further, Annexin A5 inhibited HSP-induced activation of mDCs and also oxidized low-density lipoprotein-induced HSP-production from mDCs. Experiments on mDCs and T cells derived from carotid atherosclerotic plaques from patients with symptomatic carotid disease gave similar results as from blood donors. HSP60 induces mDCs activation and partly major histocompatibility complex class II-dependent activation of blood- and plaque-derived T cells, which is mostly of Th1/Th17 type. HSP60 could thus be an important T-cell antigen in plaques, and also mediate oxidized low-density lipoproteins immunogenic effects on DC-T-cell activation, promoting plaque rupture and clinical manifestations of cardiovascular disease. Annexin A5 inhibits both oxidized low-density lipoprotein-induced HSP60, and HSP60-mediated immune activation, which suggests a potential therapeutic role. © 2017 The Authors. Published on behalf of the

  3. The polysialic acid mimetics idarubicin and irinotecan stimulate neuronal survival and neurite outgrowth and signal via protein kinase C.

    Science.gov (United States)

    Loers, Gabriele; Astafiev, Steven; Hapiak, Yuliya; Saini, Vedangana; Mishra, Bibhudatta; Gul, Sheraz; Kaur, Gurcharan; Schachner, Melitta; Theis, Thomas

    2017-08-01

    Polysialic acid (PSA) is a large, negatively charged, linear homopolymer of alpha2-8-linked sialic acid residues. It is generated by two polysialyltransferases and attached to N- and/or O-linked glycans, and its main carrier is the neural cell adhesion molecule (NCAM). PSA controls the development and regeneration of the nervous system by enhancing cell migration, axon pathfinding, synaptic targeting, synaptic plasticity, by regulating the differentiation of progenitor cells and by modulating cell-cell and cell-matrix adhesions. In the adult, PSA plays a role in the immune system, and PSA mimetics promote functional recovery after nervous system injury. In search for novel small molecule mimetics of PSA that are applicable for therapy, we identified idarubicin, an antineoplastic anthracycline, and irinotecan, an antineoplastic agent of the topoisomerase I inhibitor class, as PSA mimetics using a competition enzyme-linked immunosorbent assay. Idarubicin and irinotecan compete with the PSA-mimicking peptide and colominic acid, the bacterial analog of PSA, for binding to the PSA-specific monoclonal antibody 735. Idarubicin and irinotecan stimulate neurite outgrowth and survival of cultured cerebellar neurons after oxidative stress via protein kinase C and Erk1/2 in a similar manner as colominic acid, whereas Fyn, casein kinase II and the phosphatase and tensin homolog are only involved in idarubicin and irinotecan-stimulated neurite outgrowth. These novel results show that the structure and function of PSA can be mimicked by the small organic compounds irinotecan and idarubicin which trigger the same signaling cascades as PSA, thus introducing the possibility of retargeting these drugs to treat nervous system injuries. © 2017 International Society for Neurochemistry.

  4. Sialidase NEU4 hydrolyzes polysialic acids of neural cell adhesion molecules and negatively regulates neurite formation by hippocampal neurons.

    Science.gov (United States)

    Takahashi, Kohta; Mitoma, Junya; Hosono, Masahiro; Shiozaki, Kazuhiro; Sato, Chihiro; Yamaguchi, Kazunori; Kitajima, Ken; Higashi, Hideyoshi; Nitta, Kazuo; Shima, Hiroshi; Miyagi, Taeko

    2012-04-27

    Modulation of levels of polysialic acid (polySia), a sialic acid polymer, predominantly associated with the neural cell adhesion molecule (NCAM), influences neural functions, including synaptic plasticity, neurite growth, and cell migration. Biosynthesis of polySia depends on two polysialyltransferases ST8SiaII and ST8SiaIV in vertebrate. However, the enzyme involved in degradation of polySia in its physiological turnover remains uncertain. In the present study, we identified and characterized a murine sialidase NEU4 that catalytically degrades polySia. Murine NEU4, dominantly expressed in the brain, was found to efficiently hydrolyze oligoSia and polySia chains as substrates in sialidase in vitro assays, and also NCAM-Fc chimera as well as endogenous NCAM in tissue homogenates of postnatal mouse brain as assessed by immunoblotting with anti-polySia antibodies. Degradation of polySia by NEU4 was also evident in neuroblastoma Neuro2a cells that were co-transfected with Neu4 and ST8SiaIV genes. Furthermore, in mouse embryonic hippocampal primary neurons, the endogenously expressed NEU4 was found to decrease during the neuronal differentiation. Interestingly, GFP- or FLAG-tagged NEU4 was partially co-localized with polySia in neurites and significantly suppressed their outgrowth, whereas silencing of NEU4 showed the acceleration together with an increase in polySia expression. These results suggest that NEU4 is involved in regulation of neuronal function by polySia degradation in mammals.

  5. The adaptor protein SH2B3 (Lnk negatively regulates neurite outgrowth of PC12 cells and cortical neurons.

    Directory of Open Access Journals (Sweden)

    Tien-Cheng Wang

    Full Text Available SH2B adaptor protein family members (SH2B1-3 regulate various physiological responses through affecting signaling, gene expression, and cell adhesion. SH2B1 and SH2B2 were reported to enhance nerve growth factor (NGF-induced neuronal differentiation in PC12 cells, a well-established neuronal model system. In contrast, SH2B3 was reported to inhibit cell proliferation during the development of immune system. No study so far addresses the role of SH2B3 in the nervous system. In this study, we provide evidence suggesting that SH2B3 is expressed in the cortex of embryonic rat brain. Overexpression of SH2B3 not only inhibits NGF-induced differentiation of PC12 cells but also reduces neurite outgrowth of primary cortical neurons. SH2B3 does so by repressing NGF-induced activation of PLCγ, MEK-ERK1/2 and PI3K-AKT pathways and the expression of Egr-1. SH2B3 is capable of binding to phosphorylated NGF receptor, TrkA, as well as SH2B1β. Our data further demonstrate that overexpression of SH2B3 reduces the interaction between SH2B1β and TrkA. Consistent with this finding, overexpressing the SH2 domain of SH2B3 is sufficient to inhibit NGF-induced neurite outgrowth. Together, our data demonstrate that SH2B3, unlike the other two family members, inhibits neuronal differentiation of PC12 cells and primary cortical neurons. Its inhibitory mechanism is likely through the competition of TrkA binding with the positive-acting SH2B1 and SH2B2.

  6. Validity and reliability of autofluorescence-based quantification method of dental plaque.

    Science.gov (United States)

    Han, Sun-Young; Kim, Bo-Ra; Ko, Hae-Youn; Kwon, Ho-Keun; Kim, Baek-Il

    2015-12-01

    The aim of this study was to evaluate validity and reliability of autofluorescence-based plaque quantification (APQ) method. The facial surfaces of 600 sound anterior teeth of 50 subjects were examined. The subjects received dental plaque examination using Turesky modified Quigley Hein plaque index (QHI) and Silness & Löe plaque index (SLI). The autofluorescence images were taken before the plaque examination with Quantitative Light-induced Fluorescence-Digital, and plaque percent index (PPI) was calculated. Correlation between two existing plaque indices and the PPI of the APQ method was evaluated to find which level of plaque redness on tooth (ΔR) by the APQ method shows the highest correlation. The area under the ROC curve (AUC) analysis and intra- and inter-examiner reliability tests were performed. The PPIΔR20 of the APQ method showed a moderate correlation with two existing plaque indices (rho of QHI=0.48, SLI=0.51). This methodology fell in the fair category and it had an excellent reliability. The APQ method also showed possibility to detect heavy plaque with fair validity. The APQ method demonstrated excellent reliability, and fair validity, compared with 2 conventional indices. The plaque quantification described has the potential to be used in clinical evaluation of oral hygiene procedures. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Role of Ox-LDL/LOX-1/NF-κB signaling pathway in regulation of atherosclerotic plaque growth by testosterone in male rabbits.

    Science.gov (United States)

    Li, Shijun; Guo, Yuanyuan; Zhu, Ping; Yang, Tingshu

    2013-01-01

    The purpose of our study is to investigate the role of oxidized low density lipoprotein (Ox-LDL)/lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1)/nuclear factor-κB (NF-κB) signaling pathway in the regulation of atherosclerotic plaque growth by testosterone in male atherosclerotic rabbits. The male rabbit model was prepared by castration and feeding cholesterol-rich diet. Pathological sections of thoracic aorta were performed hematoxylin-eosin staining to observe aortic morphological changes. Total serum testosterone was measured with chemical luminescent method. Serum Ox-LDL, soluble intercellular adhesion molecule-1 (sICAM-1) and matrix metalloproteinases-2 (MMP2) were assayed using ELISA kit following the manufacturer's instructions. Serum tumor necrosis factor α (TNFα) and interleukin-6 (IL6) were assayed using radioimmunoassay. Expressions of LOX-1 of thoracic aorta were measured by RT-PCR, immunohistochemistry and Western blot methods respectively. There was no significant difference in Ox-LDL level between all groups. The LOX-1 mRNA and protein expression of thoracic aorta were significantly higher in the castrated rabbits as compared with the sham-operated ones, and testosterone replacement could reduce the mRNA and protein expression of LOX-1 of thoracic aorta in the castrated rabbits. PIA reduced artery intima thickness and plaque area in castrated rabbits, which was further enhanced by testosterone replacement. PDTC reduced artery intima thickness and plaque area in castrated rabbits, which couldn't be enhanced by testosterone replacement. Our study demonstrates that testosterone can regulate atherosclerotic plaque progression, affect expression of LOX-1 and NF-κB in thoracic aorta and play a role in atherosclerotic plaque growth via NF-κB rather than Ox-LDL or LOX-1 in male rabbits. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Effect of dental plaque control on infection of Helicobacter pylori in gastric mucosa.

    Science.gov (United States)

    Jia, Chun-Ling; Jiang, Guang-Shui; Li, Chun-Hai; Li, Cui-Rong

    2012-10-01

    Data on the role of dental plaque in the transmission of Helicobactor pylori have varied. Furthermore, there has been few reports on the relationship between dental plaque control and H. pylori infection of gastric mucosa. The purpose of this study was to elucidate this potential relationship. The 13C urea breath test was conducted on 56 subjects who received dental plaque control and 51 subjects who did not. The prevalence of H. pylori in the gastric mucosa was 19.64% in patients who received dental plaque control, which was significantly lower than in those without dental plaque control (84.31%). Long-term professional dental plaque control was associated with less gastric reinfection by H. pylori, suggesting that dental plaque control may help to prevent H. pylori-induced gastric disease or reinfection.

  9. Efficacy of triphala mouth rinse (aqueous extracts) on dental plaque and gingivitis in children.

    Science.gov (United States)

    Bhattacharjee, Ritesh; Nekkanti, Sridhar; Kumar, Nikesh G; Kapuria, Ketan; Acharya, Shashidhar; Pentapati, Kalyana C

    2015-08-01

    The aim of the present study was to evaluate the efficacy of triphala mouth rinse (aqueous) in the reduction of plaque and gingivitis among children. The study was a randomized, double-blinded, controlled trial, with a total of 60 school children (n = 30 in each group; triphala and chlorhexidine groups). Plaque and gingival indices were used to evaluate baseline and follow-up plaque and gingivitis. A total of 57 children completed the study. Both chlorhexidine and triphala groups showed significantly lower mean gingival and plaque index scores at follow up than baseline (P plaque index was significantly higher in the chlorhexidine group compared to the triphala group (P = 0.048). The effectiveness of triphala in the reduction of plaque and gingivitis was comparable to chlorhexidine, and can be used for short-term purposes without potential side-effects. It is a cost-effective alternative in reducing plaque and gingivitis. © 2014 Wiley Publishing Asia Pty Ltd.

  10. Texture based segmentation method to detect atherosclerotic plaque from optical tomography images

    Science.gov (United States)

    Prakash, Ammu; Hewko, Mark; Sowa, Michael; Sherif, Sherif

    2013-06-01

    Optical coherence tomography (OCT) imaging has been widely employed in assessing cardiovascular disease. Atherosclerosis is one of the major cause cardio vascular diseases. However visual detection of atherosclerotic plaque from OCT images is often limited and further complicated by high frame rates. We developed a texture based segmentation method to automatically detect plaque and non plaque regions from OCT images. To verify our results we compared them to photographs of the vascular tissue with atherosclerotic plaque that we used to generate the OCT images. Our results show a close match with photographs of vascular tissue with atherosclerotic plaque. Our texture based segmentation method for plaque detection could be potentially used in clinical cardiovascular OCT imaging for plaque detection.

  11. Ustekinumab in the therapy of chronic plaque psoriasis

    Directory of Open Access Journals (Sweden)

    Jenna L O’Neill

    2009-03-01

    Full Text Available Jenna L O’Neill, Robert E KalbState University of New York at Buffalo, School of Medicine and Biomedical Sciences, Department of Dermatology, NY, USAAbstract: Psoriasis is a chronic inflammatory disorder characterized by T cell dysregulation and a chronic inflammatory infiltrate within the epidermis. Several cytokines play an important role in the pathogenesis of psoriasis, including interleukin-12 (IL-12 and IL-23. These cytokines act via induction of pro-inflammatory cytokines which promote chronic inflammation and auto-reactivity. Ustekinumab is a fully human monoclonal antibody against the common p40 subunit of IL-12 and IL-23. Two randomized, double-blind, placebo-controlled trials of ustekinumab have demonstrated significant and prolonged efficacy in the treatment of plaque psoriasis. Adverse events were generally similar across treatment and control groups. Studies are ongoing to assess the long term safety and efficacy profiles of ustekinumab.Keywords: ustekinumab, psoriasis, plaque

  12. Apollo 11 Commander Armstrong Presents President With Commemorative Plaque

    Science.gov (United States)

    1974-01-01

    On June 4, 1974, 5 years after the successful Apollo 11 lunar landing mission, commander Neil Armstrong (right) presented a plaque to U.S. President Richard Milhous Nixon (left) on behalf of all people who had taken part in the space program. In making the presentation, Armstrong said 'Mr. President, you have proclaimed this week to be United States Space week in conjunction with the fifth anniversary of our first successful landing on the Moon. It is my privilege to represent my colleagues, the crewmen of projects Mercury, Gemini, Apollo, and Skylab, and the men and women of NASA, and the hundreds of thousands of Americans from across the land who contributed so mightily to the success of our efforts in space in presenting this plaque which bears the names of each individual who has had the privilege of representing this country' in a space flight. The presentation was made at the California white house in San Clemente.

  13. Primary pleural lymphoma: plaque-like thickening of the pleura.

    Science.gov (United States)

    Oikonomou, Anastasia; Giatromanolaki, Alexandra; Margaritis, Dimitrios; Froudarakis, Marios; Prassopoulos, Panos

    2010-01-01

    Primary pleural lymphoma is a rare entity that has been described in association with human immunodeficiency virus (HIV) infection or pyothorax. We report a 63-year-old-man with no history of HIV infection or pyothorax who presented with progressive dyspnea and nonproductive cough. Chest radiography revealed complete opacification of the left hemithorax, and contrast-enhanced computed tomography showed large left pleural effusion and thin, homogeneous, plaque-like thickening of the parietal pleura. Thoracoscopic pleural biopsy was consistent with grade 1 extranodal follicular lymphoma of the pleura. The authors suggest that physicians should be aware of this rare location of primary pleural lymphoma manifested by plaque-like thickening of the pleura but not accompanied by mediastinal lymphadenopathy.

  14. Inhibition of dental plaque formation by toothpaste containing propolis

    Directory of Open Access Journals (Sweden)

    Nurin Aisyiyah Listyasari

    2012-12-01

    Full Text Available Background: Plaque is the main cause of caries and periodontal disease. Caries and periodontal disease can be prevented by inhibiting dental plaque formation. To inhibit the formation of plaque, teeth must be brushed with toothpaste. According to previous studies, propolis contains apigenin and tt-farnesol classified as flavonoid that can inhibit the formation of dental plaque by inhibiting glucosyltransferase enzym and membrane integrity of Streptococcus mutans. Purpose: The aim of this study was to determine the effect of toothpaste containing propolis on the formation of dental plaque. Methods: Post test with only control group design was used. The subjects of this study were 30 boarding school students of Hidayatullah, Yayasan Al-Burhan, Gedawang, Semarang, divided into two groups, randomized control group and treatment group. Control group was not treated with toothpaste contanining propolis. Meanwhile, treatment group was treated with toothpaste containing propolis. Plaque then was measured by using plaque index of Sillness and Loe method after using toothpaste containing propolis for four hours. Afterwards, the data was analyzed by a computer program, Mann-Whitney test, with its significance p < 0.05. Results: The result of Mann-Whitney test showed a significant difference, 0.002 (p < 0.05, between the control group and the treatment group. The median of the control group was about 3.41, while that of the treatment group was about 0.58. Conclusion: The use of toothpaste contaning propolis can prevent dental plaque formation.Latar belakang: Plak merupakan penyebab utama terjadinya karies dan penyakit periodontal. Karies dan penyakit periodontal dapat dicegah dengan menghambat pembentukan plak gigi. Untuk mencegah terbentuknya plak, gigi harus digosok menggunakan pasta gigi. Penelitian terdahulu menyebutkan bahwa propolis mengandung flavonoid apigenin dan tt-farnesol yang mampu menghambat aktivitas enzim glukosiltransferase dan menghambat

  15. Definition of human rotavirus serotypes by plaque reduction assay.

    Science.gov (United States)

    Wyatt, R G; Greenberg, H B; James, W D; Pittman, A L; Kalica, A R; Flores, J; Chanock, R M; Kapikian, A Z

    1982-07-01

    Twenty different human rotavirus reassortants were characterized serologically by a plaque reduction assay as belonging to one of three distinct serotypes. Fourteen were similar if not identical to our prototype Wa strain; two were like the prototype DS-1 strain, and four belonged to a third serotype for which a prototype has not yet been selected. Hyperimmune sera raised against the three serotypes were required to distinguish among them, since postinfection sera had lower titers and were more cross-reactive than hyperimmune sera. These results confirmed the ability of a qualitative cytopathic neutralization test to predict correctly the Wa or DS-1 serotype. A strain of rhesus rotavirus (MMU 18006) was identified as belonging to the newly defined third serotype. Finally, an attempt was made to correlate previously published serotype analysis by neutralization of fluorescent cell-forming units with the results determined by the plaque reduction neutralization assay.

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

    Science.gov (United States)

    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.

  17. Multiple viral plaques with sebaceous differentiation associated with an unclassified papillomavirus type in a cat.

    Science.gov (United States)

    Munday, J S; Marshall, S; Thomson, N A; Kiupel, M; Heathcott, R W; French, A

    2017-07-01

    CASE HISTORY AND CLINICAL FINDINGS A 15-year-old neutered male domestic short-haired cat was presented due to multiple 0.5-2 cm-diameter crusting plaques in the left preauricular region, over the bridge of nose, and in the right periocular region. The plaques did not appear to cause discomfort. HISTOPATHOLOGICAL FINDINGS Biopsy samples of four plaques were examined histologically. Three plaques consisted of well-demarcated foci of mild epidermal hyperplasia overlying markedly hyperplastic sebaceous glands. Approximately 60% of the hyperplastic cells contained a large cytoplasmic vacuole that ranged from being clear to containing prominent grey-blue fibrillar material. The fourth plaque was composed solely of epidermal hyperplasia, consistent with previous descriptions of feline viral plaques. MOLECULAR BIOLOGY Papillomavirus DNA was amplified from all four plaques using PCR. A single DNA sequence was amplified from the plaques with sebaceous differentiation. This sequence was identical to the FdPV-MY sequence previously suggested to be from a putative unclassified papillomavirus type. Felis catus papillomavirus type 2 sequences were amplified from the plaque typical of feline viral plaques. Immunohistochemistry to detect p16 CDKN2A protein (p16) showed marked immunostaining throughout the hyperplastic epidermis and adnexal structures within the plaques with sebaceous differentiation. DIAGNOSIS Multiple feline viral plaques with variable sebaceous differentiation. CLINICAL RELEVANCE Feline viral plaques with sebaceous differentiation have not been previously reported in cats. The presence of unique cell changes within these lesions, the detection of an unclassified papillomavirus type, and the p16 immunostaining within these plaques suggest that they may have been caused by the papillomavirus that contains the FdPV-MY sequence.

  18. Dynamics of red fluorescent dental plaque during experimental gingivitis--A cohort study.

    Science.gov (United States)

    van der Veen, Monique H; Volgenant, Catherine M C; Keijser, Bart; Ten Cate, Jacob Bob M; Crielaard, Wim

    2016-05-01

    The dynamics of red fluorescent plaque (RFP) in comparison to clinical plaque and bleeding scores were studied during an experimental gingivitis protocol in a cohort of healthy participants. Forty-one participants were monitored for RFP before (24h plaque), during 14 days plaque accumulation (days 2, 5, 9, 14) and after 7 days recovery (24h plaque). RFP was assessed on fluorescence photographs of the vestibular aspect of the anterior teeth (cuspid to cuspid) in the upper and lower jaw. Clinical plaque and bleeding were assessed at days -14, 0, 14 and 21. RFP of 24h plaque was reproducible (days -14, 0), then increased during 14 days plaque accumulation and returned to baseline after 7 days recovery. Groups of low, moderate and high RFP formers were statistically significantly different at all times even already at baseline. The individual RFP response during 14 days plaque accumulation correlated well with RFP of 24h plaque (days -14, 0). RFP correlated moderate to well with clinical plaque at days -14, 0, 14 and 21. From day 2 of the gingivitis challenge RFP correlated with bleeding at day 14. RFP provided an objective measure of oral hygiene status. Given the correlation with clinical parameters found, the amount of RFP after 24h plaque accumulation was indicatory for the inflammatory response during a prolonged period of no oral hygiene. This trial was registered at the public trial register ​of the Central Committee on Research Involving Human Subjects (CCMO) under number NL51111.029.14 CLINICAL SIGNIFICANCE: This paper shows the association between RFP after 24h plaque accumulation and inflammatory response after a prolonged period of no oral hygiene. Red plaque fluorescence can be used to identify subjects at risk for developing gingival inflammation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Low Bone Density

    Science.gov (United States)

    ... Density Exam/Testing › Low Bone Density Low Bone Density Low bone density is when your bone density ... people with normal bone density. Detecting Low Bone Density A bone density test will determine whether you ...

  20. A rotational ablation tool for calcified atherosclerotic plaque removal.

    Science.gov (United States)

    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.