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Sample records for active ms lesions

  1. Reduced raft-association of NF155 in active MS-lesions is accompanied by the disruption of the paranodal junction.

    PubMed

    Maier, Olaf; Baron, Wia; Hoekstra, Dick

    2007-06-01

    Neurofascin155 (NF155) is required for the establishment of the paranodal axo-glial junction, the predominant interaction site between myelin and axon. It has been shown that the distribution of NF155 is altered in demyelinating diseases such as multiple sclerosis (MS). However, little is known about the biochemical mechanisms underlying these changes. We therefore compared NF155 in postmortem tissue of active and chronic inactive MS lesions with white matter from healthy controls. Although NF155 showed a very similar expression in all control white matter samples, a strong individual variation was observed in MS-lesions with NF155-levels reduced in most samples. At the same time an NF155-fragment was increased in MS-lesions, suggesting that NF155 is subject to protein degradation in lesion sites. Interestingly, the association of NF155 to membrane microdomains (rafts) was reduced in all lesions, irrespective of the amount of NF155, indicating that membrane association of NF155 was generally affected. Therefore, myelin fractionation experiments were performed to analyze the fate of paranodal proteins during demyelination. Although NF155 was enriched in heavy myelin from both control white matter and active MS-lesions, association of Caspr1/paranodin with heavy myelin was abolished in MS-lesions, demonstrating that paranodal junctions are disrupted. In conclusion, the data support the hypothesis that efficient raft-association of NF155 is essential for the assembly of the paranodal junction and demonstrate that reduced association of NF155 to lipid rafts is accompanied by the disassembly of the paranodal junction and thus contributes to the demyelination process in MS. PMID:17405145

  2. Computer-aided tracking of MS lesions

    NASA Astrophysics Data System (ADS)

    Sturm, Deborah; Gurwitz Kletenik, Devorah; Koshy, Philip

    2011-03-01

    Multiple Sclerosis (MS) lesions are known to change over time. The location, size and shape characteristics of lesions are often used to diagnose and to track disease progression. We have improved our lesion-browsing tool that allows users to automatically locate successive significant lesions in a MRI stack. In addition, an automatic alignment feature was implemented to facilitate comparisons across stacks. A lesion stack is formed that can be browsed independently or in tandem with the image windows. Lesions of interest can then be measured, rendered and rotated. Multiple windows allow the viewer to compare the size and shape of lesions from the MRI images of the same patient taken at different time intervals.

  3. MS Cortical Lesions on DIR: Not Quite What They Seem?

    PubMed Central

    Sethi, Varun; Muhlert, Nils; Ron, Maria; Golay, Xavier; Wheeler-Kingshott, Claudia A.; Miller, David H.; Chard, Declan T.; Yousry, Tarek A.

    2013-01-01

    Objective Accurate identification and localization of cortical gray matter (CGM) lesions in MS is important when determining their clinical relevance. Double inversion recovery (DIR) scans have been widely used to detect MS CGM lesions. Phase sensitive inversion recovery (PSIR) scans have a higher signal to noise, and can therefore be obtained at a higher resolution within clinically acceptable times. This enables detection of more CGM lesions depicting a clearer cortical and juxtacortical anatomy. In this study, we systematically investigated if the use of high resolution PSIR scans changes the classification of CGM lesions, when compared with standard resolution DIR scans. Methods 60 patients [30 RR(Relapsing remitting) and 15 each with PP(Primary progressive) and SP(Secondary progressive) MS] were scanned on a 3T Philips Achieva MRI scanner. Images acquired included DIR (1×1×3 mm resolution) and PSIR (0.5×0.5×2 mm). CGM lesions were detected and classified on DIR as intracortical (IC) or leucocortical (LC). We then examined these lesions on corresponding slices of the high resolution PSIR scans and categorized them as IC, LC, Juxtacortical white matter (JC-WM, abutting but not entering cortex) and other white matter (WM, not juxtacortical). Classifications using both scans were noted. Results 282 IC and 483 LC were identified on DIR. Of the IC lesions, 61% were confirmed as IC on PSIR, 35.5% were reclassified as LC and 3.5% as JC-WM or other WM only. Of the LC DIR lesions, 43.9% were confirmed at LC on PSIR, 16.1% were reclassified as IC and 40% as JC-WM or other WM only. Overall, 50% (381/765) of CGM lesions seen on DIR were reclassified, and 26.5% (203/765) affected WM only. Conclusions When compared with higher resolution PSIR, a significant proportion of lesions classified as involving CGM on DIR appear to either contain more white matter than expected or to not involve CGM at all. PMID:24244381

  4. Detection and quantification of MS lesions using fuzzy topological principles

    NASA Astrophysics Data System (ADS)

    Udupa, Jayaram K.; Wei, Luogang; Samarasekera, Supun; Miki, Yukio; van Buchem, M. A.; Grossman, Robert I.

    1996-04-01

    Quantification of the severity of the multiple sclerosis (MS) disease through estimation of lesion volume via MR imaging is vital for understanding and monitoring the disease and its treatment. This paper presents a novel methodology and a system that can be routinely used for segmenting and estimating the volume of MS lesions via dual-echo spin-echo MR imagery. An operator indicates a few points in the images by pointing to the white matter, the gray matter, and the CSF. Each of these objects is then detected as a fuzzy connected set. The holes in the union of these objects correspond to potential lesion sites which are utilized to detect each potential lesion as a fuzzy connected object. These 3D objects are presented to the operator who indicates acceptance/rejection through the click of a mouse button. The volume of accepted lesions is then computed and output. Based on several evaluation studies and over 300 3D data sets that were processed, we conclude that the methodology is highly reliable and consistent, with a coefficient of variation (due to subjective operator actions) of less than 1.0% for volume.

  5. Texture Analysis of T2-Weighted MR Images to Assess Acute Inflammation in Brain MS Lesions

    PubMed Central

    Michoux, Nicolas; Guillet, Alain; Rommel, Denis; Mazzamuto, Giosué; Sindic, Christian; Duprez, Thierry

    2015-01-01

    Brain blood barrier breakdown as assessed by contrast-enhanced (CE) T1-weighted MR imaging is currently the standard radiological marker of inflammatory activity in multiple sclerosis (MS) patients. Our objective was to evaluate the performance of an alternative model assessing the inflammatory activity of MS lesions by texture analysis of T2-weighted MR images. Twenty-one patients with definite MS were examined on the same 3.0T MR system by T2-weighted, FLAIR, diffusion-weighted and CE-T1 sequences. Lesions and mirrored contralateral areas within the normal appearing white matter (NAWM) were characterized by texture parameters computed from the gray level co-occurrence and run length matrices, and by the apparent diffusion coefficient (ADC). Statistical differences between MS lesions and NAWM were analyzed. ROC analysis and leave-one-out cross-validation were performed to evaluate the performance of individual parameters, and multi-parametric models using linear discriminant analysis (LDA), partial least squares (PLS) and logistic regression (LR) in the identification of CE lesions. ADC and all but one texture parameter were significantly different within white matter lesions compared to within NAWM (p < 0.0167). Using LDA, an 8-texture parameter model identified CE lesions with a sensitivity Se = 70% and a specificity Sp = 76%. Using LR, a 10-texture parameter model performed better with Se = 86% / Sp = 84%. Using PLS, a 6-texture parameter model achieved the highest accuracy with Se = 88% / Sp = 81%. Texture parameter from T2-weighted images can assess brain inflammatory activity with sufficient accuracy to be considered as a potential alternative to enhancement on CE T1-weighted images. PMID:26693908

  6. Texture Analysis of T2-Weighted MR Images to Assess Acute Inflammation in Brain MS Lesions.

    PubMed

    Michoux, Nicolas; Guillet, Alain; Rommel, Denis; Mazzamuto, Giosué; Sindic, Christian; Duprez, Thierry

    2015-01-01

    Brain blood barrier breakdown as assessed by contrast-enhanced (CE) T1-weighted MR imaging is currently the standard radiological marker of inflammatory activity in multiple sclerosis (MS) patients. Our objective was to evaluate the performance of an alternative model assessing the inflammatory activity of MS lesions by texture analysis of T2-weighted MR images. Twenty-one patients with definite MS were examined on the same 3.0T MR system by T2-weighted, FLAIR, diffusion-weighted and CE-T1 sequences. Lesions and mirrored contralateral areas within the normal appearing white matter (NAWM) were characterized by texture parameters computed from the gray level co-occurrence and run length matrices, and by the apparent diffusion coefficient (ADC). Statistical differences between MS lesions and NAWM were analyzed. ROC analysis and leave-one-out cross-validation were performed to evaluate the performance of individual parameters, and multi-parametric models using linear discriminant analysis (LDA), partial least squares (PLS) and logistic regression (LR) in the identification of CE lesions. ADC and all but one texture parameter were significantly different within white matter lesions compared to within NAWM (p < 0.0167). Using LDA, an 8-texture parameter model identified CE lesions with a sensitivity Se = 70% and a specificity Sp = 76%. Using LR, a 10-texture parameter model performed better with Se = 86% / Sp = 84%. Using PLS, a 6-texture parameter model achieved the highest accuracy with Se = 88% / Sp = 81%. Texture parameter from T2-weighted images can assess brain inflammatory activity with sufficient accuracy to be considered as a potential alternative to enhancement on CE T1-weighted images. PMID:26693908

  7. Changed histone acetylation patterns in normal appearing white matter and early MS lesions

    PubMed Central

    Pedre, X; Mastronardi, F.; Bruck, W.; López-Rodas, G; Kuhlmann, T; Casaccia, P

    2011-01-01

    The epigenetic identity of oligodendrocytes is modulated by post-translational modifications of histones. Acetylation of histone H3 results from the balance between the activity of histone-acetyltransferases (HATs) and histone deacetylases (HDACs) and modulates transcriptional activation. We have previously shown that in rodents histone deacetylation favors oligodendrocyte differentiation, while acetylation is associated with increased levels of transcriptional inhibitors of oligodendrocyte differentiation. Here we report in humans brains, a shift towards histone acetylation in the white matter of the frontal lobes of aged subjects and in patients with chronic multiple sclerosis (MS). Increased immunoreactivity for acetylated histone H3 was observed in the nuclei of NogoA+ oligodendrocytes in a subset of MS samples. These changes were associated with high levels of transcriptional inhibitors of oligodendrocyte differentiation (i.e. TCF7L2, ID2 and SOX2) and higher HAT transcript levels (i.e. CBP, P300) in female MS patients compared to non-neurological controls and correlated with disease duration. Chromatin immunoprecipitation from samples of MS patients revealed enrichment of acetyl-histone H3 at the promoter of the increased target genes (i.e. TCF7L2). The data in chronic lesions contrasted with findings in early MS lesions, where a marked oligodendroglial histone deacetylation was observed. Together these data suggest that histone deacetylation is a process that occurs at the early stages of the disease and whose efficiency decreases with disease duration. PMID:21368055

  8. Individual Assessment of Brain Tissue Changes in MS and the Effect of Focal Lesions on Short-Term Focal Atrophy Development in MS: A Voxel-Guided Morphometry Study

    PubMed Central

    Fox, Jan; Kraemer, Matthias; Schormann, Thorsten; Dabringhaus, Andreas; Hirsch, Jochen; Eisele, Philipp; Szabo, Kristina; Weiss, Christel; Amann, Michael; Weier, Katrin; Naegelin, Yvonne; Kappos, Ludwig; Gass, Achim

    2016-01-01

    We performed voxel-guided morphometry (VGM) investigating the mechanisms of brain atrophy in multiple sclerosis (MS) related to focal lesions. VGM maps detect regional brain changes when comparing 2 time points on high resolution T1-weighted (T1w) magnetic resonace imaging (MRI). Two T1w MR datasets from 92 relapsing-remitting MS patients obtained 12 months apart were analysed with VGM. New lesions and volume changes of focal MS lesions as well as in the surrounding tissue were identified by visual inspection on colour coded VGM maps. Lesions were dichotomized in active and inactive lesions. Active lesions, defined by either new lesions (NL) (volume increase > 5% in VGM), chronic enlarging lesions (CEL) (pre-existent T1w lesions with volume increase > 5%), or chronic shrinking lesions (CSL) (pre-existent T1w lesions with volume reduction > 5%) in VGM, were accompanied by tissue shrinkage in surrounding and/or functionally related regions. Volume loss within the corpus callosum was highly correlated with the number of lesions in its close proximity. Volume loss in the lateral geniculate nucleus was correlated with lesions along the optic radiation. VGM analysis provides strong evidence that all active lesion types (NL, CEL, and CSL) contribute to brain volume reduction in the vicinity of lesions and/or in anatomically and functionally related areas of the brain. PMID:27043553

  9. Non-Local Means Inpainting of MS Lesions in Longitudinal Image Processing.

    PubMed

    Guizard, Nicolas; Nakamura, Kunio; Coupé, Pierrick; Fonov, Vladimir S; Arnold, Douglas L; Collins, D Louis

    2015-01-01

    In medical imaging, multiple sclerosis (MS) lesions can lead to confounding effects in automatic morphometric processing tools such as registration, segmentation and cortical extraction, and subsequently alter individual longitudinal measurements. Multiple magnetic resonance imaging (MRI) inpainting techniques have been proposed to decrease the impact of MS lesions in medical image processing, however, most of these methods make the assumption that lesions only affect white matter. Here, we propose a method to fill lesion regions using the patch-based non-local mean (NLM) strategy. The method consists of a hierarchical concentric filling strategy after identification of the lesion region. The lesion is filled iteratively, based on the surrounding tissue intensity, using an onion peel strategy. This concentric technique presents the advantage of preserving the local information and therefore the continuity of the anatomy and does not require identification of any a priori normal brain tissues. The method is first evaluated on 20 healthy subjects with simulated artificial MS lesions where we assessed our technique by measuring the peak signal-to-noise ratio (PSNR) of the images with inpainted lesion and the original healthy images. Second, in order to assess the impact of lesion filling on longitudinal image analyses, we performed a power analysis with sample size estimation to evaluate brain atrophy and ventricular growth in patients with MS. The method was compared to two different publicly available methods (FSL lesion fill and Lesion LEAP) and a more classic method, which fills the region with intensities similar to that of the surrounding healthy white matter tissue or mask the lesions. The proposed method was shown to exceed the other methods in reproducing the fidelity of healthy subject images where the lesions were inpainted. The method also improved the power to detect brain atrophy or ventricular growth by decreasing the sample size by 25% in the presence

  10. Non-Local Means Inpainting of MS Lesions in Longitudinal Image Processing

    PubMed Central

    Guizard, Nicolas; Nakamura, Kunio; Coupé, Pierrick; Fonov, Vladimir S.; Arnold, Douglas L.; Collins, D. Louis

    2015-01-01

    In medical imaging, multiple sclerosis (MS) lesions can lead to confounding effects in automatic morphometric processing tools such as registration, segmentation and cortical extraction, and subsequently alter individual longitudinal measurements. Multiple magnetic resonance imaging (MRI) inpainting techniques have been proposed to decrease the impact of MS lesions in medical image processing, however, most of these methods make the assumption that lesions only affect white matter. Here, we propose a method to fill lesion regions using the patch-based non-local mean (NLM) strategy. The method consists of a hierarchical concentric filling strategy after identification of the lesion region. The lesion is filled iteratively, based on the surrounding tissue intensity, using an onion peel strategy. This concentric technique presents the advantage of preserving the local information and therefore the continuity of the anatomy and does not require identification of any a priori normal brain tissues. The method is first evaluated on 20 healthy subjects with simulated artificial MS lesions where we assessed our technique by measuring the peak signal-to-noise ratio (PSNR) of the images with inpainted lesion and the original healthy images. Second, in order to assess the impact of lesion filling on longitudinal image analyses, we performed a power analysis with sample size estimation to evaluate brain atrophy and ventricular growth in patients with MS. The method was compared to two different publicly available methods (FSL lesion fill and Lesion LEAP) and a more classic method, which fills the region with intensities similar to that of the surrounding healthy white matter tissue or mask the lesions. The proposed method was shown to exceed the other methods in reproducing the fidelity of healthy subject images where the lesions were inpainted. The method also improved the power to detect brain atrophy or ventricular growth by decreasing the sample size by 25% in the presence

  11. MS lesion segmentation using a multi-channel patch-based approach with spatial consistency

    NASA Astrophysics Data System (ADS)

    Mechrez, Roey; Goldberger, Jacob; Greenspan, Hayit

    2015-03-01

    This paper presents an automatic method for segmentation of Multiple Sclerosis (MS) in Magnetic Resonance Images (MRI) of the brain. The approach is based on similarities between multi-channel patches (T1, T2 and FLAIR). An MS lesion patch database is built using training images for which the label maps are known. For each patch in the testing image, k similar patches are retrieved from the database. The matching labels for these k patches are then combined to produce an initial segmentation map for the test case. Finally a novel iterative patch-based label refinement process based on the initial segmentation map is performed to ensure spatial consistency of the detected lesions. A leave-one-out evaluation is done for each testing image in the MS lesion segmentation challenge of MICCAI 2008. Results are shown to compete with the state-of-the-art methods on the MICCAI 2008 challenge.

  12. A comparison of supervised machine learning algorithms and feature vectors for MS lesion segmentation using multimodal structural MRI.

    PubMed

    Sweeney, Elizabeth M; Vogelstein, Joshua T; Cuzzocreo, Jennifer L; Calabresi, Peter A; Reich, Daniel S; Crainiceanu, Ciprian M; Shinohara, Russell T

    2014-01-01

    Machine learning is a popular method for mining and analyzing large collections of medical data. We focus on a particular problem from medical research, supervised multiple sclerosis (MS) lesion segmentation in structural magnetic resonance imaging (MRI). We examine the extent to which the choice of machine learning or classification algorithm and feature extraction function impacts the performance of lesion segmentation methods. As quantitative measures derived from structural MRI are important clinical tools for research into the pathophysiology and natural history of MS, the development of automated lesion segmentation methods is an active research field. Yet, little is known about what drives performance of these methods. We evaluate the performance of automated MS lesion segmentation methods, which consist of a supervised classification algorithm composed with a feature extraction function. These feature extraction functions act on the observed T1-weighted (T1-w), T2-weighted (T2-w) and fluid-attenuated inversion recovery (FLAIR) MRI voxel intensities. Each MRI study has a manual lesion segmentation that we use to train and validate the supervised classification algorithms. Our main finding is that the differences in predictive performance are due more to differences in the feature vectors, rather than the machine learning or classification algorithms. Features that incorporate information from neighboring voxels in the brain were found to increase performance substantially. For lesion segmentation, we conclude that it is better to use simple, interpretable, and fast algorithms, such as logistic regression, linear discriminant analysis, and quadratic discriminant analysis, and to develop the features to improve performance. PMID:24781953

  13. Patch-Based Segmentation with Spatial Consistency: Application to MS Lesions in Brain MRI.

    PubMed

    Mechrez, Roey; Goldberger, Jacob; Greenspan, Hayit

    2016-01-01

    This paper presents an automatic lesion segmentation method based on similarities between multichannel patches. A patch database is built using training images for which the label maps are known. For each patch in the testing image, k similar patches are retrieved from the database. The matching labels for these k patches are then combined to produce an initial segmentation map for the test case. Finally an iterative patch-based label refinement process based on the initial segmentation map is performed to ensure the spatial consistency of the detected lesions. The method was evaluated in experiments on multiple sclerosis (MS) lesion segmentation in magnetic resonance images (MRI) of the brain. An evaluation was done for each image in the MICCAI 2008 MS lesion segmentation challenge. Results are shown to compete with the state of the art in the challenge. We conclude that the proposed algorithm for segmentation of lesions provides a promising new approach for local segmentation and global detection in medical images. PMID:26904103

  14. Evaluation of an automatic multiple sclerosis lesion quantification tool in an informatics-based MS e-folder system

    NASA Astrophysics Data System (ADS)

    Ma, Kevin; Fernandez, James; Amezcua, Lilyana; Lerner, Alex; Liu, Brent

    2011-03-01

    Multiple sclerosis (MS) is a demyelinating disease of the central nervous system. The chronic nature of MS necessitates multiple MRI studies to track disease progression. We have presented an imaging informatics decision-support system, called MS eFolder, designed to integrate patient clinical data with MR images and a computer-aided detection (CAD) component for automatic white matter lesion quantification. The purpose of the MS eFolder is to comprehensively present MS patient data for clinicians and radiologists, while providing a lesion quantification tool that can be objective and consistent for MS tracking in longitudinal studies. The MS CAD algorithm is based on the K-nearest neighbor (KNN) principles and has been integrated within the eFolder system. Currently, the system has been completed and the CAD algorithm for quantifying MS lesions has undergone the expert evaluation in order to validate system performance and accuracy. The evaluation methodology has been developed and the data has been collected, including over 100 MS MRI cases with various age and ethnic backgrounds. The preliminary results of the evaluation are expected to include sensitivity and specificity of lesion and non-lesion voxels in the white matter, the effectiveness of different probability thresholds for each voxel, and comparison between CAD quantification results and radiologists' manual readings. The results aim to show the effectiveness of a MS lesion CAD system to be used in a clinical setting, as well as a step closer to full clinical implementation of the eFolder system.

  15. Automated segmentation of MS lesions in FLAIR, DIR and T2-w MR images via an information theoretic approach

    NASA Astrophysics Data System (ADS)

    Hill, Jason E.; Matlock, Kevin; Pal, Ranadip; Nutter, Brian; Mitra, Sunanda

    2016-03-01

    Magnetic Resonance Imaging (MRI) is a vital tool in the diagnosis and characterization of multiple sclerosis (MS). MS lesions can be imaged with relatively high contrast using either Fluid Attenuated Inversion Recovery (FLAIR) or Double Inversion Recovery (DIR). Automated segmentation and accurate tracking of MS lesions from MRI remains a challenging problem. Here, an information theoretic approach to cluster the voxels in pseudo-colorized multispectral MR data (FLAIR, DIR, T2-weighted) is utilized to automatically segment MS lesions of various sizes and noise levels. The Improved Jump Method (IJM) clustering, assisted by edge suppression, is applied to the segmentation of white matter (WM), gray matter (GM), cerebrospinal fluid (CSF) and MS lesions, if present, into a subset of slices determined to be the best MS lesion candidates via Otsu's method. From this preliminary clustering, the modal data values for the tissues can be determined. A Euclidean distance is then used to estimate the fuzzy memberships of each brain voxel for all tissue types and their 50/50 partial volumes. From these estimates, binary discrete and fuzzy MS lesion masks are constructed. Validation is provided by using three synthetic MS lesions brains (mild, moderate and severe) with labeled ground truths. The MS lesions of mild, moderate and severe designations were detected with a sensitivity of 83.2%, and 88.5%, and 94.5%, and with the corresponding Dice similarity coefficient (DSC) of 0.7098, 0.8739, and 0.8266, respectively. The effect of MRI noise is also examined by simulated noise and the application of a bilateral filter in preprocessing.

  16. Evolution of MS lesions to black holes under DNA vaccine treatment.

    PubMed

    Papadopoulou, Athina; von Felten, Stefanie; Traud, Stefan; Rahman, Amena; Quan, Joanne; King, Robert; Garren, Hideki; Steinman, Lawrence; Cutter, Gary; Kappos, Ludwig; Radue, Ernst Wilhelm

    2012-07-01

    Persistent black holes (PBH) are associated with axonal loss and disability progression in multiple sclerosis (MS). The objective of this work was to determine if BHT-3009, a DNA plasmid-encoding myelin basic protein (MBP), reduces the risk of new lesions becoming PBH, compared to placebo, and to test if pre-treatment serum anti-MBP antibody levels impact on the effect of BHT-3009 treatment. In this retrospective, blinded MRI study, we reviewed MRI scans of 155 MS patients from a double-blind, randomized, phase II trial with three treatment arms (placebo, 0.5 and 1.5 mg BHT-3009). New lesions at weeks 8 and 16 were tracked at week 48 and those appearing as T1-hypointense were classified as PBH. A subset of 46 patients with available pre-treatment serum anti-MBP IgM levels were analyzed separately. Overall, there was no impact of treatment on the risk for PBH. However, there was a significant interaction between anti-MBP antibodies and treatment effect: patients receiving 0.5 mg BHT-3009 showed a reduced risk of PBH with higher antibody levels compared to placebo (p < 0.01). Although we found no overall reduction of the risk for PBH in treated patients, there may be an effect of low-dose BHT-3009, depending on the patients' pre-treatment immune responses.

  17. Decreased microglial activation in MS patients treated with glatiramer acetate

    PubMed Central

    Ratchford, John N.; Endres, Christopher J.; Hammoud, Dima A.; Pomper, Martin G.; Shiee, Navid; McGready, John; Pham, Dzung L.; Calabresi, Peter A.

    2012-01-01

    Activated microglia are thought to be an important contributor to tissue damage in multiple sclerosis (MS). The level of microglial activation can be measured non-invasively using [11C]-R-PK11195, a radiopharmaceutical for positron emission tomography (PET). Prior studies have identified abnormalities in the level of [11C]-R-PK11195 uptake in patients with MS, but treatment effects have not been evaluated. Nine previously untreated relapsing-remitting MS patients underwent PET and magnetic resonance imaging (MRI) of the brain at baseline and after one year of treatment with glatiramer acetate. Parametric maps of [11C]-R-PK11195 uptake were obtained for baseline and post-treatment PET scans, and the change in [11C]-R-PK11195 uptake pre- to post-treatment was evaluated across the whole brain. Region of interest analysis was also applied to selected subregions. Whole brain [11C]-R-PK11195 binding potential per unit volume decreased 3.17% (95% CI: −0.74%, −5.53%) between baseline and one year (p = 0.018). A significant decrease was noted in cortical gray matter and cerebral white matter, and a trend towards decreased uptake was seen in the putamen and thalamus. The results are consistent with a reduction in inflammation due to treatment with glatiramer acetate, though a larger controlled study would be required to prove that association. Future research will focus on whether the level of baseline microglial activation predicts future tissue damage in MS and whether [11C]-R-PK11195 uptake in cortical gray matter correlates with cortical lesion load. PMID:22160466

  18. An automatic quantification system for MS lesions with integrated DICOM structured reporting (DICOM-SR) for implementation within a clinical environment

    NASA Astrophysics Data System (ADS)

    Jacobs, Colin; Ma, Kevin; Moin, Paymann; Liu, Brent

    2010-03-01

    Multiple Sclerosis (MS) is a common neurological disease affecting the central nervous system characterized by pathologic changes including demyelination and axonal injury. MR imaging has become the most important tool to evaluate the disease progression of MS which is characterized by the occurrence of white matter lesions. Currently, radiologists evaluate and assess the multiple sclerosis lesions manually by estimating the lesion volume and amount of lesions. This process is extremely time-consuming and sensitive to intra- and inter-observer variability. Therefore, there is a need for automatic segmentation of the MS lesions followed by lesion quantification. We have developed a fully automatic segmentation algorithm to identify the MS lesions. The segmentation algorithm is accelerated by parallel computing using Graphics Processing Units (GPU) for practical implementation into a clinical environment. Subsequently, characterized quantification of the lesions is performed. The quantification results, which include lesion volume and amount of lesions, are stored in a structured report together with the lesion location in the brain to establish a standardized representation of the disease progression of the patient. The development of this structured report in collaboration with radiologists aims to facilitate outcome analysis and treatment assessment of the disease and will be standardized based on DICOM-SR. The results can be distributed to other DICOM-compliant clinical systems that support DICOM-SR such as PACS. In addition, the implementation of a fully automatic segmentation and quantification system together with a method for storing, distributing, and visualizing key imaging and informatics data in DICOM-SR for MS lesions improves the clinical workflow of radiologists and visualizations of the lesion segmentations and will provide 3-D insight into the distribution of lesions in the brain.

  19. Optical Assessment of Caries Lesion Structure and Activity

    NASA Astrophysics Data System (ADS)

    Lee, Robert Chulsung

    New, more sophisticated diagnostic tools are needed for the detection and characterization of caries lesions in the early stages of development. It is not sufficient to simply detect caries lesions, methods are needed to assess the activity of the lesion and determine if chemical or surgical intervention is needed. Previous studies have demonstrated that polarization sensitive optical coherence tomography (PS-OCT) can be used to nondestructively image the subsurface lesion structure and measure the thickness of the highly mineralized surface zone. Other studies have demonstrated that the rate of dehydration can be correlated with the lesion activity and that the rate can be measured using optical methods. The main objective of this work was to test the hypothesis that optical methods can be used to assess lesion activity on tooth coronal and root surfaces. Simulated caries models were used to develop and validate an algorithm for detecting and measuring the highly mineralized surface layer using PS-OCT. This work confirmed that the algorithm was capable of estimating the thickness of the highly mineralized surface layer with high accuracy. Near-infrared (NIR) reflectance and thermal imaging methods were used to assess activity of caries lesions by measuring the state of lesion hydration. NIR reflectance imaging performed the best for artificial enamel and natural coronal caries lesion samples, particularly at wavelengths coincident with the water absorption band at 1460-nm. However, thermal imaging performed the best for artificial dentin and natural root caries lesion samples. These novel optical methods outperformed the conventional methods (ICDAS II) in accurately assessing lesion activity of natural coronal and root caries lesions. Infrared-based imaging methods have shown potential for in-vivo applications to objectively assess caries lesion activity in a single examination. It is likely that if future clinical trials are a success, this novel imaging

  20. Detection activity assessment and diagnosis of dental caries lesions.

    PubMed

    Braga, Mariana M; Mendes, Fausto M; Ekstrand, Kim R

    2010-07-01

    This article reviews the current methods for detection and assessment of caries lesions focusing on applicability for daily clinical practice. The end point is to arrive at a diagnosis for each caries lesion. Visual inspection aided by a ball-ended probe is essential for caries lesions assessment and the method must be used for all patients. Use of indices, for example, the International Caries Detection and Assessment System (ICDAS), can improve the performance of this method. Using visual inspection, the clinician must decide about the presence, severity and activity of lesions. After this process, additional methods could aid the dentist in reaching a more appropriate treatment decision in some cases. The ICDAS, including the activity assessment system or the Nyvad system, seems to be the best option to reach final diagnoses for managing lesions. The radiographic method is the most recommended additional method available for daily clinical practice.

  1. MS/MS analysis of the products of toluene photooxidation and measurement of their mutagenic activity

    SciTech Connect

    Dumdel, B.E.; Kenny, D.V.; Shepson, P.B.; Kleindienst, T.E.; Nero, C.M.; Cupitt, L.T.; Claxton, L.D.

    1988-12-01

    Products of the photooxidation of toluene from an irradiated 5.1 ppm toluene/0.9 ppm NO/sub x/ mixture were identified by use of a triple-quadrupole MS/MS operated in an atmospheric pressure ionization mode. The reaction was carried out in a flow-mode 22.7-m/sup 3/ Telfon smog chamber. The steady-state reactant and product mixture was continuously transferred to the mass spectrometer inlet at 144 L/min. By using structurally similar standards, semiquantitative MS/MS analyses for many of the ring fragmentation products were conducted. Quantitative analyses by chromatographic methods and semiquantitative analyses by MS/MS were conducted for a variety of ring fragmentation products. The following products were found with yields of 1% (C/C) or greater: methylglyoxal, glyoxal, benzaldehyde, methylbutenedial, hydroxy-methylbutenedial, peroxyacetyl nitrate, oxoheptadienal, CH/sub 3/COOH, HCHO, hexadienal, and hydroxyoxo-heptadienal. The mutagenic activity of the steady-state product mixture was measured by using the Ames assay Salmonella typhimurium strain TA 100. The mutagenic activity data are discussed relative to our earlier findings that resulted from different reaction conditions.

  2. Nucleus accumbens core lesions enhance two-way active avoidance

    PubMed Central

    Lichtenberg, Nina T.; Kashtelyan, Vadim; Burton, Amanda C.; Bissonette, Gregory B.; Roesch, Matthew R.

    2014-01-01

    The majority of work examining nucleus accumbens core (NAc) has focused on functions pertaining to behaviors guided by appetitive outcomes. These studies have pointed to NAc as being critical for motivating behavior toward desirable outcomes. For example, we have recently shown that lesions of NAc impaired performance on a reward-guided decision-making task that required rats to choose between differently valued rewards. Unfortunately, much less is known about the role that NAc plays in motivating behavior when aversive outcomes are predicted. To address this issue we asked if NAc lesions impact performance on a two-way active avoidance task in which rats must learn to shuttle back and forth in a behavioral training box in order to avoid a footshock predicted by an auditory tone. Although bilateral NAc lesions initially impaired reward-guided decision-making, we found that the same lesions improved acquisition and retention of two-way active avoidance. PMID:24275320

  3. Visualization of time-varying MRI data for MS lesion analysis

    NASA Astrophysics Data System (ADS)

    Tory, Melanie K.; Moeller, Torsten; Atkins, M. Stella

    2001-05-01

    Conventional methods to diagnose and follow treatment of Multiple Sclerosis require radiologists and technicians to compare current images with older images of a particular patient, on a slic-by-slice basis. Although there has been progress in creating 3D displays of medical images, little attempt has been made to design visual tools that emphasize change over time. We implemented several ideas that attempt to address this deficiency. In one approach, isosurfaces of segmented lesions at each time step were displayed either on the same image (each time step in a different color), or consecutively in an animation. In a second approach, voxel- wise differences between time steps were calculated and displayed statically using ray casting. Animation was used to show cumulative changes over time. Finally, in a method borrowed from computational fluid dynamics (CFD), glyphs (small arrow-like objects) were rendered with a surface model of the lesions to indicate changes at localized points.

  4. Phase-Sensitive Inversion-Recovery MRI Improves Longitudinal Cortical Lesion Detection in Progressive MS

    PubMed Central

    Farrell, Colleen; Fabian, Michelle; Howard, Jonathan; Riley, Claire; Miller, Aaron; Lublin, Fred; Inglese, Matilde

    2016-01-01

    Previous studies comparing phase sensitive inversion recovery (PSIR) to double inversion recovery (DIR) have demonstrated that use of PSIR improves cross-sectional in vivo detection of cortical lesions (CL) in multiple sclerosis. We studied the utility of PSIR in detection/characterization of accrual of CL over time in a 1-year longitudinal study in primary progressive multiple sclerosis (PPMS) compared to DIR. PSIR and DIR images were acquired with 3T magnetic resonance imaging (MRI) in 25 patients with PPMS and 19 healthy controls at baseline, and after 1 year in 20 patients with PPMS. CL were classified as intracortical, leucocortical or juxtacortical. Lesion counts and volumes were calculated for both time points from both sequences and compared. Correlations with measures of physical and cognitive disability were determined as well as new CL counts and volumes. Compared to DIR, PSIR led to detection of a higher number of CL involving a larger proportion of patients with PPMS both cross-sectionally (p = 0.006, 88%) and longitudinally (p = 0.007, 95%), and led to the reclassification of a third of CL seen on DIR at each time point. Interestingly, PSIR was more sensitive to new CL accumulation over time compared to DIR. PSIR is a promising technique to monitor cortical damage and disease progression in patients with PPMS over a short-term follow-up. PMID:27002529

  5. Phase-Sensitive Inversion-Recovery MRI Improves Longitudinal Cortical Lesion Detection in Progressive MS.

    PubMed

    Harel, Asaff; Ceccarelli, Antonia; Farrell, Colleen; Fabian, Michelle; Howard, Jonathan; Riley, Claire; Miller, Aaron; Lublin, Fred; Inglese, Matilde

    2016-01-01

    Previous studies comparing phase sensitive inversion recovery (PSIR) to double inversion recovery (DIR) have demonstrated that use of PSIR improves cross-sectional in vivo detection of cortical lesions (CL) in multiple sclerosis. We studied the utility of PSIR in detection/characterization of accrual of CL over time in a 1-year longitudinal study in primary progressive multiple sclerosis (PPMS) compared to DIR. PSIR and DIR images were acquired with 3T magnetic resonance imaging (MRI) in 25 patients with PPMS and 19 healthy controls at baseline, and after 1 year in 20 patients with PPMS. CL were classified as intracortical, leucocortical or juxtacortical. Lesion counts and volumes were calculated for both time points from both sequences and compared. Correlations with measures of physical and cognitive disability were determined as well as new CL counts and volumes. Compared to DIR, PSIR led to detection of a higher number of CL involving a larger proportion of patients with PPMS both cross-sectionally (p = 0.006, 88%) and longitudinally (p = 0.007, 95%), and led to the reclassification of a third of CL seen on DIR at each time point. Interestingly, PSIR was more sensitive to new CL accumulation over time compared to DIR. PSIR is a promising technique to monitor cortical damage and disease progression in patients with PPMS over a short-term follow-up.

  6. Metatranscriptomics reveals overall active bacterial composition in caries lesions

    PubMed Central

    Simón-Soro, Aurea; Guillen-Navarro, Miriam; Mira, Alex

    2014-01-01

    Background Identifying the microbial species in caries lesions is instrumental to determine the etiology of dental caries. However, a significant proportion of bacteria in carious lesions have not been cultured, and the use of molecular methods has been limited to DNA-based approaches, which detect both active and inactive or dead microorganisms. Objective To identify the RNA-based, metabolically active bacterial composition of caries lesions at different stages of disease progression in order to provide a list of potential etiological agents of tooth decay. Design Non-cavitated enamel caries lesions (n=15) and dentin caries lesions samples (n=12) were collected from 13 individuals. RNA was extracted and cDNA was constructed, which was used to amplify the 16S rRNA gene. The resulting 780 bp polymerase chain reaction products were pyrosequenced using Titanium-plus chemistry, and the sequences obtained were used to determine the bacterial composition. Results A mean of 4,900 sequences of the 16S rRNA gene with an average read length of 661 bp was obtained per sample, giving a comprehensive view of the active bacterial communities in caries lesions. Estimates of bacterial diversity indicate that the microbiota of cavities is highly complex, each sample containing between 70 and 400 metabolically active species. The composition of these bacterial consortia varied among individuals and between caries lesions of the same individuals. In addition, enamel and dentin lesions had a different bacterial makeup. Lactobacilli were found almost exclusively in dentin cavities. Streptococci accounted for 40% of the total active community in enamel caries, and 20% in dentin caries. However, Streptococcus mutans represented only 0.02–0.73% of the total bacterial community. Conclusions The data indicate that the etiology of dental caries is tissue dependent and that the disease has a clear polymicrobial origin. The low proportion of mutans streptococci detected confirms that they

  7. Detection of endocrine active substances in the aquatic environment in southern Taiwan using bioassays and LC-MS/MS.

    PubMed

    Chen, Kuang-Yu; Chou, Pei-Hsin

    2016-06-01

    Endocrine active substances, including naturally occurring hormones and various synthetic chemicals have received much concern owing to their endocrine disrupting potencies. It is essential to monitor their environmental occurrence since these compounds may pose potential threats to biota and human health. In this study, yeast-based reporter assays were carried out to investigate the presence of (anti-)androgenic, (anti-)estrogenic, and (anti-)thyroid compounds in the aquatic environment in southern Taiwan. Liquid chromatography tandem mass spectrometry (LC-MS/MS) was also used to measure the environmental concentrations of selected endocrine active substances for assessing potential ecological risks and characterizing contributions to the endocrine disrupting activities. Bioassay results showed that anti-androgenic (ND-7489 μg L(-1) flutamide equivalent), estrogenic (ND-347 ng L(-1) 17β-estradiol equivalent), and anti-thyroid activities were detected in the dissolved and particulate phases of river water samples, while anti-estrogenic activities (ND-10 μg L(-1) 4-hydroxytamoxifen equivalent) were less often found. LC-MS/MS analysis revealed that anti-androgenic and estrogenic contaminants, such as bisphenol A, triclosan, and estrone were frequently detected in Taiwanese rivers. In addition, their risk quotient values were often higher than 1, suggesting that they may pose an ecological risk to the aquatic biota. Further identification of unknown anti-androgenic and estrogenic contaminants in Taiwanese rivers may be necessary to protect Taiwan's aquatic environment. PMID:26971174

  8. Characterization of aroma-active and phenolic profiles of wild thyme (Thymus serpyllum) by GC-MS-Olfactometry and LC-ESI-MS/MS.

    PubMed

    Sonmezdag, Ahmet Salih; Kelebek, Hasim; Selli, Serkan

    2016-04-01

    The present study was designed to characterize the volatile, aroma-active and phenolic compounds of wild thyme. Volatile components of T. serpyllum were extracted by use of the purge and trap technique with dichloromethane and analyzed by gas chromatography-mass spectrometry (GC-MS). The extraction method gave highly representative aromatic extract of the studied sample based on the sensory analysis. A total of 24 compounds were identified and quantified in Thymus serpyllum. Terpenes were qualitatively and quantitatively the most dominant volatiles in the sample. Aroma extract dilution analysis (AEDA) was used for the first time for the determination of aroma-active compounds of Thymus serpyllum. In total, 12 aroma-active compounds were detected in the aromatic extract by GC-MS-Olfactometry and terpenes were the most abundant compounds. High-performance liquid chromatography/electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) method was used for the phenolic compounds analysis. 18 phenolic compounds were identified and quantified in the T. serpyllum. Luteolin 7-O-glucoside, luteolin and rosmarinic acid were the most abundant phenolics in this herb. PMID:27413222

  9. Topographic congruence of calcified parenchymal neurocysticercosis and other structural brain lesions with epileptiform activity

    PubMed Central

    Saito, Erin K; Nagpal, Meera; Leon, Amanda; Mehta, Bijal; McMurtray, Aaron Matthew

    2016-01-01

    Introduction: Calcified parenchymal neurocysticercosis (NCC) lesions are commonly detected in many individuals with refractory epilepsy. However, the relationship between these lesions and epilepsy is not fully determined. We sought to determine if calcified parenchymal NCC demonstrated topographic congruence with epileptiform activity in refractory epilepsy patients. Additional patients with other structural brain lesions were included for comparison. Subjects and Methods: Retrospective cross-sectional analysis of all patients treated at a community-based neurology clinic for refractory epilepsy during a 3-month period and with structural brain lesions detected by neuroimaging studies. Results: A total of 105 patients were included in the study, including 63 with calcified parenchymal NCC lesions and 42 with other structural brain lesions. No significant relationship was detected between hemispheric localization of calcified parenchymal NCC lesions and epileptiform activity. For those with other structural brain lesions, the hemispheric localization was significantly related to the side of epileptiform activity (Chi-square = 11.13, P = 0.025). In addition, logistic regression models showed that those with right-sided non-NCC lesions were more likely to have right-sided epileptiform activity (odds ratio = 4.36, 95% confidence interval [CI] =1.16–16.31, P = 0.029), and those with left-sided non-NCC lesions were more likely to have left-sided epileptiform activity (odds ratio = 7.60, 95% CI = 1.89–30.49, P = 0.004). Conclusion: The lack of correlation between the side of calcified parenchymal NCC lesions and the side of the epileptiform activity suggests that these lesions may be incidental findings in many patients. PMID:26998434

  10. The use of non-linear analysis for differentiating the biomagnetic activity in ovarian lesions.

    PubMed

    Anninos, P A; Anastasiadis, P; Kotini, A

    1999-05-01

    In this study we investigated the biomagnetic activity measured with the superconducting quantum interference device (SQUID) in benign and malignant ovarian lesions using non-linear analysis. We used a single channel biomagnetometer SQUID in order to measure the magnetic field emitted from benign and malignant ovarian lesions. We can differentiate such biomagnetic activities using non-linear analysis. Using the application of non-linear analysis in the ovarian lesions together with the use of dimensional calculations we have observed a clear saturation value for the dimension of malignant ovarian lesions and non-saturation for benign ovarian lesions. The biomagnetic measurements with the SQUID and the application of non-linear analysis in benign and malignant ovarian lesions, is a promising procedure in assessing and differentiating ovarian tumours. PMID:15512296

  11. Isotopic signature of selected lanthanides for nuclear activities profiling using cloud point extraction and ICP-MS/MS.

    PubMed

    Labrecque, Charles; Lebed, Pablo J; Larivière, Dominic

    2016-05-01

    The presence of fission products, which include numerous isotopes of lanthanides, can impact the isotopic ratios of these elements in the environment. A cloud point extraction (CPE) method was used as a preconcentration/separation strategy prior to measurement of isotopic ratios of three lanthanides (Nd, Sm, and Eu) by inductively coupled plasma tandem mass spectrometry (ICP-MS/MS). To minimise polyatomic interference, the combination of interferents removal by CPE, reaction/collision cell conditions in He and NH3 mode and tandem quadrupole configuration was investigated and provided optimal results for the determination of isotopic ratio in environmental samples. Isotopic ratios were initially measured in San Joaquin soil (NIST-2709a), an area with little contamination of nuclear origin. Finally, samples collected from three sites with known nuclear activities (Fangataufa Lagoon in French Polynesia, Chernobyl and the Ottawa River near Chalk River Laboratory) were analysed and all exhibited altered isotopic ratios for (143/145)Nd, (147/149)Sm, and (151/153)Eu. These results demonstrate the potential of CPE and ICP-MS/MS for the detection of altered isotopic ratio in environmental samples collected in area subjected to nuclear anthropogenic contamination. The detection of variations in these isotopic ratios of fission products represents the first application of CPE in nuclear forensic investigations of environmental samples. PMID:26895346

  12. Isotopic signature of selected lanthanides for nuclear activities profiling using cloud point extraction and ICP-MS/MS.

    PubMed

    Labrecque, Charles; Lebed, Pablo J; Larivière, Dominic

    2016-05-01

    The presence of fission products, which include numerous isotopes of lanthanides, can impact the isotopic ratios of these elements in the environment. A cloud point extraction (CPE) method was used as a preconcentration/separation strategy prior to measurement of isotopic ratios of three lanthanides (Nd, Sm, and Eu) by inductively coupled plasma tandem mass spectrometry (ICP-MS/MS). To minimise polyatomic interference, the combination of interferents removal by CPE, reaction/collision cell conditions in He and NH3 mode and tandem quadrupole configuration was investigated and provided optimal results for the determination of isotopic ratio in environmental samples. Isotopic ratios were initially measured in San Joaquin soil (NIST-2709a), an area with little contamination of nuclear origin. Finally, samples collected from three sites with known nuclear activities (Fangataufa Lagoon in French Polynesia, Chernobyl and the Ottawa River near Chalk River Laboratory) were analysed and all exhibited altered isotopic ratios for (143/145)Nd, (147/149)Sm, and (151/153)Eu. These results demonstrate the potential of CPE and ICP-MS/MS for the detection of altered isotopic ratio in environmental samples collected in area subjected to nuclear anthropogenic contamination. The detection of variations in these isotopic ratios of fission products represents the first application of CPE in nuclear forensic investigations of environmental samples.

  13. Serotonergic changes in specific areas of rat brain associated with activity--stress gastric lesions.

    PubMed

    Hellhammer, D H; Hingtgen, J N; Wade, S E; Shea, P A; Aprison, M H

    1983-05-01

    To study serotonergic involvement in the development of gastric lesions following activity wheel stress, three groups of rats (gastric lesions, no gastric lesions, and home--cage controls) were killed following exposure to the experimental procedures. The brains were dissected into eight specific areas and subjected to analyses for serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) using high performance liquid chromatography with EC detection. Lower levels of 5-HT were found in the midbrain, cortex, and hippocampus of rats with gastric lesions compared to either the no lesion group, subjected to shorter periods of activity--stress, or the home--cage control group. Levels of 5-HT and 5-HIAA were elevated in the pons/medulla oblongata of both the lesion and the no lesion groups compared to the home--cage controls. Corticosterone levels in blood were also significantly elevated in the lesion group. These data on serotonin changes in the CNS suggest a possible role for this neurotransmitter in stress-induced gastric pathology. PMID:6191350

  14. Interleukin-17- and interleukin-22-secreting myelin-specific CD4(+) T cells resistant to corticoids are related with active brain lesions in multiple sclerosis patients.

    PubMed

    Wing, Ana Cristina; Hygino, Joana; Ferreira, Thais B; Kasahara, Taissa M; Barros, Priscila O; Sacramento, Priscila M; Andrade, Regis M; Camargo, Solange; Rueda, Fernanda; Alves-Leon, Soniza V; Vasconcelos, Claudia Cristina; Alvarenga, Regina; Bento, Cleonice A M

    2016-02-01

    Multiple sclerosis (MS) is thought to be an autoimmune disorder. It is believed that immunological events in the early stages have great impact on the disease course. Therefore, we aimed to evaluate the cytokine profile of myelin basic protein (MBP)-specific T cells from MS patients in the early phase of the disease and correlate it to clinical parameters, as well as to the effect of in vitro corticoid treatment. Peripheral T cells from MS patients were stimulated with MBP with our without hydrocortisone for 5 days. The cytokines level were determined by ELISA. The number of active brain lesions was determined by MRI scans, and the neurological disabilities were assessed by Expanded Disability Status Scale scores. Our results demonstrated that MS-derived T cells responded to MBP by producing high levels of T helper type 1 (Th1) and Th17 cytokines. Although the production of interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor, IL-17 and IL-22 was less sensitive to hydrocortisone inhibition, only IL-17 and IL-22 levels correlated with active brain lesions. The ability of hydrocortisone to inhibit IL-17 and IL-22 production by MBP-specific CD4(+) T cells was inversely related to the number of active brain lesions. Finally, the production of both cytokines was significantly higher in cell cultures from Afrodescendant patients and it was less sensitive to hydrocortisone inhibition. In summary, our data suggest that IL-17- and IL-22-secreting CD4(+) T cells resistant to corticoids are associated with radiological activity of the MS in early stages of the disease, mainly among Afrodescendant patients who, normally, have worse prognosis.

  15. Fish biomarkers for environmental monitoring: An integrated model supporting enzyme activity and histopathological lesions

    NASA Astrophysics Data System (ADS)

    Neta, Raimunda Nonata Fortes Carvalho; Torres Junior, Audalio Rebelo

    2014-10-01

    We present a mathematical model describing the association between glutathione-S-transferase activity and brachial lesions in the catfish, Sciades herzbergii (Ariidae) from a polluted port. The catfish were sampled from a port known to be contaminated with heavy metals and organic compounds and from a natural reserve in São Marcos Bay, Brazil. Two biomarkers, hepatic glutathione S-transferase (GST) activity and histopathological lesions, in gills tissue were measured. The values for GST activity were modeled with the occurrence of branchial lesions by fitting a third order polynomial. Results from the mathematical model indicate that GST activity has a strong polynomial relationship with the occurrence of branchial lesions in both the wet and the dry seasons, but only at the polluted port site. The model developed in this study indicates that branchial and hepatic lesions are initiated when GST activity reaches 2.15 μmol min-1 mg protein-1. Beyond this limit, GST activity decreased to very low levels and irreversible histopathological lesions occurred. This mathematical model provides a realistic approach to analyze predictive biomarkers of environmental health status.

  16. Loss of circadian rhythmicity in body temperature and locomotor activity following suprachiasmatic lesions in the rat

    NASA Technical Reports Server (NTRS)

    Saleh, M. A.; Haro, P. J.; Winget, C. M.

    1977-01-01

    In experiments on male and female ambulatory rats, the effect of bilateral suprachiasmatic lesions on deep body temperature and locomotor activity circadian rhythms was investigated. A L/D:12/12 cycle and 23 C ambient temperature were maintained. One-half of the rats received radiofrequency lesions in the suprachiasmic nucleus (SCN) while the second group were sham operated by lowering the radiofrequency electrode to the SCN without producing electrolytic lesions. Four weeks were allowed for recuperation. Autopsies were conducted to make sure that the lesions were restricted to SCN. The results show the complete disappearance of circadian rhythm in the SCN lesioned rats and only a slight diminution for the sham operated rats.

  17. Electromyographic activity of sternocleidomastoid and masticatory muscles in patients with vestibular lesions.

    PubMed

    Tartaglia, Gianluca M; Barozzi, Stefania; Marin, Federico; Cesarani, Antonio; Ferrario, Virgilio F

    2008-01-01

    This study evaluated the electromyographic characteristics of masticatory and neck muscles in subjects with vestibular lesions. Surface electromyography of the masseter, temporalis and sternocleidomastoid muscles was performed in 19 patients with Ménière's disease, 12 patients with an acute peripheral vestibular lesion, and 19 control subjects matched for sex and age. During maximum voluntary clenching, patients with peripheral vestibular lesions had the highest co-contraction of the sternocleidomastoid muscle (analysis of covariance, p=0.02), the control subjects had the smallest values, and the patients with Ménière's disease had intermediate values. The control subjects had larger standardized muscle activities than the other patient groups (p=0.001). In conclusion, during maximum voluntary tooth clenching, patients with vestibular alterations have both more active neck muscles, and less active masticatory muscles than normal controls. Results underline the importance of a more inclusive craniocervical assessment of patients with vestibular lesions.

  18. ELECTROMYOGRAPHIC ACTIVITY OF STERNOCLEIDOMASTOID AND MASTICATORY MUSCLES IN PATIENTS WITH VESTIBULAR LESIONS

    PubMed Central

    Tartaglia, Gianluca M.; Barozzi, Stefania; Marin, Federico; Cesarani, Antonio; Ferrario, Virgilio F.

    2008-01-01

    This study evaluated the electromyographic characteristics of masticatory and neck muscles in subjects with vestibular lesions. Surface electromyography of the masseter, temporalis and sternocleidomastoid muscles was performed in 19 patients with Ménière's disease, 12 patients with an acute peripheral vestibular lesion, and 19 control subjects matched for sex and age. During maximum voluntary clenching, patients with peripheral vestibular lesions had the highest co-contraction of the sternocleidomastoid muscle (analysis of covariance, p=0.02), the control subjects had the smallest values, and the patients with Ménière's disease had intermediate values. The control subjects had larger standardized muscle activities than the other patient groups (p=0.001). In conclusion, during maximum voluntary tooth clenching, patients with vestibular alterations have both more active neck muscles, and less active masticatory muscles than normal controls. Results underline the importance of a more inclusive craniocervical assessment of patients with vestibular lesions. PMID:19082397

  19. Dentin caries activity in early occlusal lesions selected to receive operative treatment

    PubMed Central

    Lehmann, Maryann; Veitz-Keenan, Analia; Matthews, Abigail G.; Vena, Donald; Grill, Ashley; Craig, Ronald G.; Curro, Frederick A.; Thompson, Van P.

    2014-01-01

    Background Members of the practice-based research network Practitioners Engaged in Applied Research and Learning (PEARL) Network investigated the dentin caries activity in early occlusal lesions and its relationship to patient age, preoperative tooth sensitivity and radio-graphic appearance, as well as its influence on preparation depth and volume. Methods PEARL Network practitioner-investigators (P-Is) (n = 45), general dentists who were trained but whose methods were not calibrated, conducted a study regarding postoperative hypersensitivity in resin-based composite restorations. The P-Is enrolled as study participants 613 patients with occlusal carious lesions that, in the P-Is’ clinical judgment, required restoration. The P-Is used baseline radiographs to assess the depth and extent of the lesions. Data for 671 restorations included baseline sensitivity; ranking of dentin caries activity on the opening of the enamel; radiographic visibility (n = 652); and measurements of preparation depth, width and length. Results P-Is found rapidly progressing dentin caries in 38.5 percent (258 of 671) of lesions and slowly progressing (and potentially inactive dentin) caries in the remainder of the lesions. Rapidly progressing caries was not related to the participant’s age or participant-reported preoperative hypersensitivity but was related to the lesion depth as seen radiographically (P < .001) and depth (P < .001) and volume (P < .001) of the preparation. Molars had slightly higher but not statistically significant levels of caries activity. Conclusion Rapidly progressing dentin caries, while present in only 38.5 percent of lesions, was related to the lesion’s radiographic appearance but not to the participant’s age or the study tooth’s pre-operative sensitivity. Clinical Implications On the basis of the low level of rapidly progressing dentin caries in this study population and the fact that slowly progressing caries can be inactive or remineralizing, the

  20. Determinant Factors of Untreated Dental Caries and Lesion Activity in Preschool Children Using ICDAS.

    PubMed

    Pinto-Sarmento, Tássia Cristina de Almeida; Abreu, Mauro Henrique; Gomes, Monalisa Cesarino; Costa, Edja Maria Melo de Brito; Martins, Carolina Castro; Granville-Garcia, Ana Flávia; Paiva, Saul Martins

    2016-01-01

    The aim of the present study was to investigate determinant factors associated with the presence of dental caries and lesion activity in preschool children. A population-based, cross-sectional study was carried out with 843 children of aged three to five years enrolled at public and private preschools in the city of Campina Grande, Brazil. A questionnaire addressing socio-demographic data and oral health care was self-administered by parents/caregivers. Three dentists previously calibrated examined the children for the diagnosis of dental caries and lesion activity using the International Caries Detection and Assessment System (ICDAS). Nutritional status was evaluated based on the body mass index. Logistic regression analysis for complex samples was performed (α = 5%). The prevalence of dental caries was 66.3%. Among the children with caries, 88.0% had active lesions. Dental caries was more prevalent in girls (OR = 1.53, 95%CI: 1.05-2.23), in children from families with a monthly household income ≤US$312.50 (OR = 2.38, 95%CI: 1.65-3.43) and those whose mothers had up to eight years of schooling (OR = 1.55, 95%CI: 1.07-2.23). Lesion activity was significantly associated with mother's schooling ≤ 8 years (OR = 2.15, 95%CI: 1.15-4.00). The prevalence rates of dental caries and lesion activity were high and mainly associated with a lower socioeconomic status and mother's schooling.

  1. Circadian distribution of motor-activity in unilaterally 6-hydroxy-dopamine lesioned rats.

    PubMed

    Baier, Paul Christian; Branisa, Pablo; Koch, Reinhard; Schindehütte, Jan; Paulus, Walter; Trenkwalder, Claudia

    2006-02-01

    Sleep abnormalities in idiopathic Parkinson's disease (PD) frequently consist in a reduction of total sleep time and efficacy and subsequent excessive daytime sleepiness. As it remains unclear whether these phenomena are part of the disease itself or result from pharmacological treatment, animal models for investigating the pathophysiology of sleep alterations in PD may add knowledge to this research area. In the present study, we investigate whether changes in circadian motor activity occur in 6-OHDA-lesioning model for PD, and allow a screening for disturbed sleep-waking behaviour. Activity measurements of six male Wistar rats with 6-OHDA-lesions in the medial forebrain bundle and six controls were carried out in two consecutive 12:12 h light-dark (LD) cycles. A computer-based video-analysis system, recording the animals' movement tracks was used. Distance travelled and number of transitions between movement periods and resting periods were determined. Although 6-OHDA-lesioned animals show a reduced locomotor activity compared to non-lesioned rats, the circadian distribution basically remained intact. However, some lesioning effects were more pronounced in the resting phase than in the activity phase, possibly paralleling nocturnal akinesia in PD. In order to further elucidate the described phenomena, it will be necessary to perform studies combining sleep recordings with locomotor activity measurements.

  2. Nuclear Receptor Activity and Liver Cancer Lesion Progression

    EPA Science Inventory

    Nuclear receptors (NRs) are ligand-activated transcription factors that control diverse cellular processes. Chronic stimulation of some NRs is a non-genotoxic mechanism of rodent liver cancer with unclear relevance to humans. We explored this question using human CAR, PXR, PPARα,...

  3. Hippocampus and two-way active avoidance conditioning: Contrasting effects of cytotoxic lesion and temporary inactivation.

    PubMed

    Wang, Jia; Bast, Tobias; Wang, Yu-Cong; Zhang, Wei-Ning

    2015-12-01

    Hippocampal lesions tend to facilitate two-way active avoidance (2WAA) conditioning, where rats learn to cross to the opposite side of a conditioning chamber to avoid a tone-signaled footshock. This classical finding has been suggested to reflect that hippocampus-dependent place/context memory inhibits 2WAA (a crossing response to the opposite side is inhibited by the memory that this is the place where a shock was received on the previous trial). However, more recent research suggests other aspects of hippocampal function that may support 2WAA learning. More specifically, the ventral hippocampus has been shown to contribute to behavioral responses to aversive stimuli and to positively modulate the meso-accumbens dopamine system, whose activation has been implicated in 2WAA learning. Permanent hippocampal lesions may not reveal these contributions because, following complete and permanent loss of hippocampal output, other brain regions may mediate these processes or because deficits could be masked by lesion-induced extra-hippocampal changes, including an upregulation of accumbal dopamine transmission. Here, we re-examined the hippocampal role in 2WAA learning in Wistar rats, using permanent NMDA-induced neurotoxic lesions and temporary functional inhibition by muscimol or tetrodotoxin (TTX) infusion. Complete hippocampal lesions tended to facilitate 2WAA learning, whereas ventral (VH) or dorsal hippocampal (DH) lesions had no effect. In contrast, VH or DH muscimol or TTX infusions impaired 2WAA learning. Ventral infusions caused an immediate impairment, whereas after dorsal infusions rats showed intact 2WAA learning for 40-50 min, before a marked deficit emerged. These data show that functional inhibition of ventral hippocampus disrupts 2WAA learning, while the delayed impairment following dorsal infusions may reflect the time required for drug diffusion to ventral hippocampus. Overall, using temporary functional inhibition, our study shows that the ventral

  4. STS-103 M.S. John Grunsfeld during TCDT activities

    NASA Technical Reports Server (NTRS)

    1999-01-01

    STS-103 Mission Specialist John M. Grunsfeld (Ph.D.) gets ready to take the wheel of a small armored personnel carrier that is part of emergency egress training during Terminal Countdown Demonstration Test (TCDT) activities. The tracked vehicle could be used by the crew in the event of an emergency at the pad during which the crew must make a quick exit from the area. The TCDT also provides simulated countdown exercises and opportunities to inspect the mission payloads in the orbiter's payload bay. STS-103 is a 'call-up' mission due to the need to replace and repair portions of the Hubble Space Telescope. Although Hubble is operating normally and conducting its scientific observations, only three of its six gyroscopes are working properly. Four EVA's are planned to make the necessary repairs and replacements on the telescope. The other STS-103 crew members are Commander Curtis L. Brown Jr., Pilot Scott J. Kelly, Steven L. Smith, C. Michael Foale (Ph.D.), (Ph.D.), and Claude Nicollier of Switzerland and Jean-Frangois Clervoy of France, who are with the European Space Agency. The mission is targeted for launch Dec. 6 at 2:37 a.m. EST.

  5. STS-103 M.S. Steven Smith during TCDT activities

    NASA Technical Reports Server (NTRS)

    1999-01-01

    STS-103 Mission Specialist Steven L. Smith gets ready to practice driving a small armored personnel carrier that is part of emergency egress training during Terminal Countdown Demonstration Test (TCDT) activities. The tracked vehicle could be used by the crew in the event of an emergency at the pad during which the crew must make a quick exit from the area. The TCDT also provides simulated countdown exercises and opportunities to inspect the mission payloads in the orbiter's payload bay. STS-103 is a 'call-up' mission due to the need to replace and repair portions of the Hubble Space Telescope. Although Hubble is operating normally and conducting its scientific observations, only three of its six gyroscopes are working properly. Four EVA's are planned to make the necessary repairs and replacements on the telescope. The other STS-103 crew members are Commander Curtis L. Brown Jr., Pilot Scott J. Kelly, and Mission Specialists John M. Grunsfeld (Ph.D.), C. Michael Foale (Ph.D.), (Ph.D.), and Claude Nicollier of Switzerland and Jean-Frangois Clervoy of France, who are with the European Space Agency. The mission is targeted for launch Dec. 6 at 2:37 a.m. EST.

  6. STS-103 M.S. Michael Foale during TCDT activities

    NASA Technical Reports Server (NTRS)

    1999-01-01

    STS-103 Mission Specialist C. Michael Foale (Ph.D.) is ready to take his turn at driving a small armored personnel carrier that is part of emergency egress training during Terminal Countdown Demonstration Test (TCDT) activities. The tracked vehicle could be used by the crew in the event of an emergency at the pad during which the crew must make a quick exit from the area. The TCDT also provides simulated countdown exercises and opportunities to inspect the mission payloads in the orbiter's payload bay. STS-103 is a 'call-up' mission due to the need to replace and repair portions of the Hubble Space Telescope. Although Hubble is operating normally and conducting its scientific observations, only three of its six gyroscopes are working properly. Four EVA's are planned to make the necessary repairs and replacements on the telescope. The other STS-103 crew members are Commander Curtis L. Brown Jr., Pilot Scott J. Kelly, and Mission Specialists Steven L. Smith , John M. Grunsfeld (Ph.D.), and Claude Nicollier of Switzerland and Jean-Frangois Clervoy of France, who are with the European Space Agency. The mission is targeted for launch Dec. 6 at 2:37 a.m. EST.

  7. Premalignant Oral Lesion Cells Elicit Increased Cytokine Production and Activation of T-cells

    PubMed Central

    JOHNSON, SARA D.; LEVINGSTON, CORINNE; YOUNG, M. RITA I.

    2016-01-01

    Background Head and neck squamous cell carcinomas (HNSCC) are known to evade the host immune response. How premalignant oral lesions modulate the immune response, however, has yet to be elucidated. Materials and Methods A mouse model of oral carcinogenesis was used to determine how mediators from premalignant oral lesion cells vs. HNSCC cells impact on immune cytokine production and activation. Results Media conditioned by premalignant lesion cells elicited an increased production of T cell-associated cytokines and proinflammatory mediators from cervical lymph node cells compared to media conditioned by HNSCC cells or media alone. In the presence of premalignant lesion cell-conditioned media, CD4+ T cell expression of the IL-2 receptor CD25 and CD8+ T cell expression of the activation marker CD69 was greater, compared to what was induced in HNSCC cell-conditioned media or media alone. Conclusion Premalignant lesion cells promote a proinflammatory environment and induce immune changes before HNSCC tumors are established. PMID:27354582

  8. Activation status of human microglia is dependent on lesion formation stage and remyelination in multiple sclerosis.

    PubMed

    Peferoen, Laura A N; Vogel, Daphne Y S; Ummenthum, Kimberley; Breur, Marjolein; Heijnen, Priscilla D A M; Gerritsen, Wouter H; Peferoen-Baert, Regina M B; van der Valk, Paul; Dijkstra, Christine D; Amor, Sandra

    2015-01-01

    Similar to macrophages, microglia adopt diverse activation states and contribute to repair and tissue damage in multiple sclerosis. Using reverse transcription-quantitative polymerase chain reaction and immunohistochemistry, we show that in vitro M1-polarized (proinflammatory) human adult microglia express the distinctive markers CD74, CD40, CD86, and CCR7, whereas M2 (anti-inflammatory) microglia express mannose receptor and the anti-inflammatory cytokine CCL22. The expression of these markers was assessed in clusters of activated microglia in normal-appearing white matter (preactive lesions) and areas of remyelination, representing reparative multiple sclerosis lesions. We show that activated microglia in preactive and remyelinating lesions express CD74, CD40, CD86, and the M2 markers CCL22 and CD209, but not mannose receptor. To examine whether this intermediate microglia profile is static or dynamic and thus susceptible to changes in the microenvironment, we polarized microglia into M1 or M2 phenotype in vitro and then subsequently treated them with the opposing polarization regimen. These studies revealed that expression of CD40, CXCL10, and mannose receptor is dynamic and that microglia, like macrophages, can switch between M1 and M2 phenotypic profiles. Taken together, our data define the differential activation states of microglia during lesion development in multiple sclerosis-affected CNS tissues and underscore the plasticity of human adult microglia in vitro.

  9. Exploratory behavior and recognition memory in medial septal electrolytic, neuro- and immunotoxic lesioned rats.

    PubMed

    Dashniani, M G; Burjanadze, M A; Naneishvili, T L; Chkhikvishvili, N C; Beselia, G V; Kruashvili, L B; Pochkhidze, N O; Chighladze, M R

    2015-01-01

    In the present study, the effect of the medial septal (MS) lesions on exploratory activity in the open field and the spatial and object recognition memory has been investigated. This experiment compares three types of MS lesions: electrolytic lesions that destroy cells and fibers of passage, neurotoxic - ibotenic acid lesions that spare fibers of passage but predominantly affect the septal noncholinergic neurons, and immunotoxin - 192 IgG-saporin infusions that only eliminate cholinergic neurons. The main results are: the MS electrolytic lesioned rats were impaired in habituating to the environment in the repeated spatial environment, but rats with immuno- or neurotoxic lesions of the MS did not differ from control ones; the MS electrolytic and ibotenic acid lesioned rats showed an increase in their exploratory activity to the objects and were impaired in habituating to the objects in the repeated spatial environment; rats with immunolesions of the MS did not differ from control rats; electrolytic lesions of the MS disrupt spatial recognition memory; rats with immuno- or neurotoxic lesions of the MS were normal in detecting spatial novelty; all of the MS-lesioned and control rats clearly reacted to the object novelty by exploring the new object more than familiar ones. Results observed across lesion techniques indicate that: (i) the deficits after nonselective damage of MS are limited to a subset of cognitive processes dependent on the hippocampus, (ii) MS is substantial for spatial, but not for object recognition memory - the object recognition memory can be supported outside the septohippocampal system; (iii) the selective loss of septohippocampal cholinergic or noncholinergic projections does not disrupt the function of the hippocampus to a sufficient extent to impair spatial recognition memory; (iv) there is dissociation between the two major components (cholinergic and noncholinergic) of the septohippocampal pathway in exploratory behavior assessed in the open

  10. Human Brain Atlas-based Multimodal MRI Analysis of Volumetry, Diffusimetry, Relaxometry and Lesion Distribution in Multiple Sclerosis Patients and Healthy Adult Controls: Implications for understanding the Pathogenesis of Multiple Sclerosis and Consolidation of Quantitative MRI Results in MS

    PubMed Central

    Hasan, Khader M.; Walimuni, Indika S.; Abid, Humaira; Datta, Sushmita; Wolinsky, Jerry S.; Narayana, Ponnada A.

    2011-01-01

    Multiple sclerosis (MS) is the most common immune-mediated disabling neurological disease of the central nervous system. The pathogenesis of MS is not fully understood. Histopathology implicates both demyelination and axonal degeneration as the major contributors to the accumulation of disability. The application of several in vivo quantitative magnetic resonance imaging (MRI) methods to both lesioned and normal-appearing brain tissue has not yet provided a solid conclusive support of the hypothesis that MS might be a diffuse disease. In this work, we adopted FreeSurfer to provide standardized macrostructure or volumetry of lesion free normal-appearing brain tissue in combination with multiple quantitative MRI metrics (T2 relaxation time, diffusion tensor anisotropy and diffusivities) that characterize tissue microstructural integrity. By incorporating a large number of healthy controls, we have attempted to separate the natural age-related change from the disease-induced effects. Our work shows elevation in diffusivity and relaxation times and reduction in volume in a number of normal-appearing white matter and gray matter structures in relapsing-remitting multiple sclerosis patients. These changes were related in part with the spatial distribution of lesions. The whole brain lesion load and age-adjusted expanded disability status score showed strongest correlations in regions such as corpus callosum with qMRI metrics that are believed to be specific markers of axonal dysfunction, consistent with histologic data of others indicating axonal loss that is independent of focal lesions. Our results support that MS at least in part has a neurodegenerative component. PMID:21978603

  11. Determinant Factors of Untreated Dental Caries and Lesion Activity in Preschool Children Using ICDAS

    PubMed Central

    Pinto-Sarmento, Tássia Cristina de Almeida; Abreu, Mauro Henrique; Gomes, Monalisa Cesarino; Costa, Edja Maria Melo de Brito; Martins, Carolina Castro; Granville-Garcia, Ana Flávia; Paiva, Saul Martins

    2016-01-01

    The aim of the present study was to investigate determinant factors associated with the presence of dental caries and lesion activity in preschool children. A population-based, cross-sectional study was carried out with 843 children of aged three to five years enrolled at public and private preschools in the city of Campina Grande, Brazil. A questionnaire addressing socio-demographic data and oral health care was self-administered by parents/caregivers. Three dentists previously calibrated examined the children for the diagnosis of dental caries and lesion activity using the International Caries Detection and Assessment System (ICDAS). Nutritional status was evaluated based on the body mass index. Logistic regression analysis for complex samples was performed (α = 5%). The prevalence of dental caries was 66.3%. Among the children with caries, 88.0% had active lesions. Dental caries was more prevalent in girls (OR = 1.53, 95%CI: 1.05–2.23), in children from families with a monthly household income ≤US$312.50 (OR = 2.38, 95%CI: 1.65–3.43) and those whose mothers had up to eight years of schooling (OR = 1.55, 95%CI: 1.07–2.23). Lesion activity was significantly associated with mother’s schooling ≤ 8 years (OR = 2.15, 95%CI: 1.15–4.00). The prevalence rates of dental caries and lesion activity were high and mainly associated with a lower socioeconomic status and mother’s schooling. PMID:26900846

  12. The association between sterilizing activity and drug distribution into tuberculosis lesions.

    PubMed

    Prideaux, Brendan; Via, Laura E; Zimmerman, Matthew D; Eum, Seokyong; Sarathy, Jansy; O'Brien, Paul; Chen, Chao; Kaya, Firat; Weiner, Danielle M; Chen, Pei-Yu; Song, Taeksun; Lee, Myungsun; Shim, Tae Sun; Cho, Jeong Su; Kim, Wooshik; Cho, Sang Nae; Olivier, Kenneth N; Barry, Clifton E; Dartois, Véronique

    2015-10-01

    Finding new treatment-shortening antibiotics to improve cure rates and curb the alarming emergence of drug resistance is the major objective of tuberculosis (TB) drug development. Using a matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging suite in a biosafety containment facility, we show that the key sterilizing drugs rifampicin and pyrazinamide efficiently penetrate the sites of TB infection in lung lesions. Rifampicin even accumulates in necrotic caseum, a critical lesion site where persisting tubercle bacilli reside. In contrast, moxifloxacin, which is active in vitro against a subpopulation of Mycobacterium tuberculosis that persists in specific niches under drug pressure and has achieved treatment shortening in mice, does not diffuse well in caseum, concordant with its failure to shorten therapy in recent clinical trials. We suggest that such differential spatial distribution and kinetics of accumulation in lesions may create temporal and spatial windows of monotherapy in specific niches, allowing the gradual development of multidrug-resistant TB. We propose an alternative working model to prioritize new antibiotic regimens based on quantitative and spatial distribution of TB drugs in the major lesion types found in human lungs. The finding that lesion penetration may contribute to treatment outcome has wide implications for TB. PMID:26343800

  13. VEGF Gene Polymorphisms Affect Serum Protein Levels and Alter Disease Activity and Synovial Lesions in Rheumatoid Arthritis

    PubMed Central

    Yi, Jin-Ping; Wu, Yu-Zhang; Yu, Nan; Yu, Zhi-Wu; Xie, Fu-Yuan; Yuan, Quan

    2016-01-01

    Background Our study investigated 2 common single-nucleotide polymorphisms (SNPs) of vascular endothelial growth factor (VEGF) for their influences on serum VEGF levels, disease activity, and synovial lesions in rheumatoid arthritis (RA). Material/Methods Clinical information and venous blood samples were collected from 98 RA patients and 100 healthy controls. Genotyping on samples from the subjects was performed using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS). Serum VEGF levels were determined using the enzyme-linked immunosorbent assay (ELISA). The synovial thickness and joint effusion of 28 joints were measured in RA patients, and total sharp score (TSS) and disease activity score (DAS) of 28 joints were recorded. Results The genotype and allele frequencies of VEGF rs833070 (G>A) and rs3025030 (G>C) were significantly different between RA group and control group (all P<0.05). VEGF rs833070 and rs3025030 polymorphisms were associated with increasing VEGF serum levels in the RA group (all P<0.01). Statistically significant difference was observed in DAS28 between the different genotypes of VEGF rs833070 in RA patients (P<0.05). Importantly, significant differences in synovial thickening, joint effusion and synovial angiogenesis were observed between the different genotypes of VEGF rs833070 and rs3025030 polymorphisms (all P<0.05). Conclusions Our study provides evidence that VEGF polymorphisms might be important indicators of disease activity and synovial lesions, and prognostic factors in evaluating the treatment effectiveness in RA. PMID:26825024

  14. Enzymatic activity of Microsporum canis and Trichophyton mentagrophytes from breeding rabbits with and without skin lesions.

    PubMed

    Cafarchia, Claudia; Figueredo, Luciana A; Coccioli, Carmela; Camarda, Antonio; Otranto, Domenico

    2012-01-01

    Microsporum canis and Trichophyton mentagrophytes are zoophilic dermatophytes which can cause skin infections in animals and humans. The clinical expression of this infection strongly varies depending on host, fungal species as well as enzyme production. No comparative studies are available on the enzymatic activities of M. canis and T. mentagrophytes isolated from breeding rabbits. Thus, the aim of this work was to assess the capability of M. canis and T. mentagrophytes isolated from rabbits both with and without lesions in producing different enzymes. The relationship of dermatophyte enzymatic activities and presence/absence of skin lesions has also been investigated. A total of 260 isolates of T. mentagrophytes and 25 isolates of M. canis sampled both from healthy and lesioned skin of rabbits, as well as from air samples of positive farms were examined. The results showed that T. mentagrophytes and M. canis from rabbits produce different enzymes. However, only elastase and gelatinase were linked to the appearance of lesions in T. mentagrophytes infections, whereas lipase in those by M. canis. PMID:22175244

  15. RAG-induced DNA lesions activate proapoptotic BIM to suppress lymphomagenesis in p53-deficient mice.

    PubMed

    Delbridge, Alex R D; Pang, Swee Heng Milon; Vandenberg, Cassandra J; Grabow, Stephanie; Aubrey, Brandon J; Tai, Lin; Herold, Marco J; Strasser, Andreas

    2016-09-19

    Neoplastic transformation is driven by oncogenic lesions that facilitate unrestrained cell expansion and resistance to antiproliferative signals. These oncogenic DNA lesions, acquired through errors in DNA replication, gene recombination, or extrinsically imposed damage, are thought to activate multiple tumor suppressive pathways, particularly apoptotic cell death. DNA damage induces apoptosis through well-described p53-mediated induction of PUMA and NOXA. However, loss of both these mediators (even together with defects in p53-mediated induction of cell cycle arrest and cell senescence) does not recapitulate the tumor susceptibility observed in p53(-/-) mice. Thus, potentially oncogenic DNA lesions are likely to also trigger apoptosis through additional, p53-independent processes. We found that loss of the BH3-only protein BIM accelerated lymphoma development in p53-deficient mice. This process was negated by concomitant loss of RAG1/2-mediated antigen receptor gene rearrangement. This demonstrates that BIM is critical for the induction of apoptosis caused by potentially oncogenic DNA lesions elicited by RAG1/2-induced gene rearrangement. Furthermore, this highlights the role of a BIM-mediated tumor suppressor pathway that acts in parallel to the p53 pathway and remains active even in the absence of wild-type p53 function, suggesting this may be exploited in the treatment of p53-deficient cancers. PMID:27621418

  16. Active and realistic passive marijuana exposure tested by three immunoassays and GC/MS in urine

    SciTech Connect

    Mule, S.J.; Lomax, P.; Gross, S.J.

    1988-05-01

    Human urine samples obtained before and after active and passive exposure to marijuana were analyzed by immune kits (Roche, Amersham, and Syva) and gas chromatography/mass spectrometry (GC/MS). Seven of eight subjects were positive for the entire five-day test period with one immune kit. The latter correlated with GC/MS in 98% of the samples. Passive inhalation experiments under conditions likely to reflect realistic exposure resulted consistently in less than 10 ng/mL of cannabinoids. The 10-100-ng/mL cannabinoid concentration range essential for detection of occasional and moderate marijuana users is thus unaffected by realistic passive inhalation.

  17. Reduced cytochrome oxidase activity in the retrosplenial cortex after lesions to the anterior thalamic nuclei.

    PubMed

    Mendez-Lopez, Magdalena; Arias, Jorge L; Bontempi, Bruno; Wolff, Mathieu

    2013-08-01

    The anterior thalamic nuclei (ATN) make a critical contribution to hippocampal system functions. Growing experimental work shows that the effects of ATN lesions often resemble those of hippocampal lesions and both markedly reduce the expression of immediate-early gene markers in the retrosplenial cortex, which still appears normal by standard histological means. This study shows that moderate ATN damage was sufficient to produce severe spatial memory impairment as measured in a radial-arm maze. Furthermore, ATN rats exhibited reduced cytochrome oxidase activity in the most superficial cortical layers of the granular retrosplenial cortex, and, to a lesser extent, in the anterior cingulate cortex. By contrast, no change in cytochrome oxidase activity was observed in other limbic cortical regions or in the hippocampal formation. Altogether our results indicate that endogenous long-term brain metabolic capacity within the granular retrosplenial cortex is compromised by even limited ATN damage.

  18. Effectiveness of the anaesthetic MS-222 in gilthead seabream, Sparus aurata: effect of feeding time and day-night variations in plasma MS-222 concentration and GST activity.

    PubMed

    Vera, L M; Montoya, A; Sánchez-Vázquez, F J

    2013-02-17

    Feeding time is a potent zeitgeber capable of synchronising behavioural and physiological daily rhythms in fish. However, the effect of feeding time on the daily rhythm of drugs toxicity and/or effectiveness remains unexplored to date. In this paper we investigated the day/night variations in the effectiveness of an anaesthetic commonly used in fish (Tricaine, MS-222) in a teleost of great chronobiological and aquaculture interest (gilthead seabream). To this end, fish were kept under LD 12:12 and fed at mid-light (ML), mid-darkness (MD) or random times (RD). The time needed to induce anaesthesia (reduction of locomotor activity) during MS-222 exposure (65 mg/L) as well as the recovery period were investigated at ML and MD in the three experimental groups using specialised video tracking software. In addition, daily rhythms of GST activity in the liver (as an indicator of detoxification processes) and plasma MS-222 concentration (related to uptake) were determined. The results revealed that MS-222 effectiveness in the ML group was higher during the day than at night (significant reduction of activity after 3 min vs. 5 min) whereas in the MD group, the daily variation of MS-222 effectiveness was inverted (significant reduction of activity after 7 min at ML vs. 2 min at MD), suggesting that feeding time can shift the day-night variations in the effectiveness of MS-222. Hepatic GST also seemed to be affected by feeding time: in fish fed at MD or RD this enzyme activity showed significant differences during the day, and the highest levels were found at different times of the day in each group. Plasma MS-222 concentrations were higher at ML (142.4±12.8 ng/ml) than at MD (96.3±10.9 ng/ml) (t-Student, p<0.05). These results suggest that the daily variation in MS-222 concentration following exposure might be involved, among other factors, in the existence of day-night variations in the effectiveness of this anaesthetic. Furthermore, manipulation of the feeding schedule

  19. Screening assay of angiotensin-converting enzyme inhibitory activity from complex natural colourants and foods using high-throughput LC-MS/MS.

    PubMed

    Inoue, Koichi; Kitade, Marie; Hino, Tomoaki; Oka, Hisao

    2011-06-15

    Inhibition of angiotensin-converting enzyme (ACE) by various foods decreases the blood pressure. ACE inhibitors derived from natural components may be of therapeutic value in preventive medicine. In this study, we report a novel screening assay of ACE inhibitors from complex natural colourants and foods that employ solid phase extraction (SPE), high-throughput liquid chromatography (LC) separation, and stable isotope dilution electrospray tandem mass spectrometry (SID-ESI-MS/MS). When a target sample was subjected to N-Hippuryl-His-Leu (HHL) and ACE in phosphate buffer (pH 7.4), generated hippuric acid (HA) was extracted by SPE. LC/SID-ESI-MS/MS detection of HA allowed us to accurately identify the effects of complex substances such natural colourants and foods that inhibit the ACE of HHL. The major HA and HA-d5 fragment ions at m/z 180→105 and 185→110 in the multiple reaction monitoring (MRM) mode can quantify levels that are lower than other methods. The LC/SID-ESI-MS/MS method described here is a rapid, selective, sensitive, and highly reproducible method for the determination of HA in various samples. Based on the assay developed, all samples such as natural colourants, infant formula, soy paste, ketchup, mayonnaise, wheat flour, orange juice, supplement drink, tea, and coffee could be accurately measured for ACE inhibition in various matrices. High-throughput LC/SID-ESI-MS/MS assay has no limitations in the evaluation of inhibition activity in various natural samples such as colour, high-matrix, and processed foods. PMID:25213976

  20. Activated inflammatory T cells correlate with lesion size in human cutaneous leishmaniasis.

    PubMed

    Antonelli, Lis R V; Dutra, Walderez O; Almeida, Roque P; Bacellar, Olivia; Carvalho, Edgar M; Gollob, Kenneth J

    2005-11-15

    Leishmaniasis is an important parasitic disease affecting millions worldwide. In attempts to understand the clinical relevance of immunological measurements as determined using flow cytometry, several immunological phenotypes were determined for a group of well defined human leishmaniasis patients and correlated with clinical measurements of the disease (Montenegro skin test (MST) and lesion area). The analysis demonstrated a positive correlation between the MST size and the frequency of ex vivo recent activated CD4(+) T cells. In contrast, higher frequencies of recent activated CD8(+) T cells were correlated with a smaller MST size. Moreover, a positive correlation was observed between the lesion total area and the frequency of activated CD69(+) (ex vivo) and CD40L(+) (cultured with Leishmania soluble antigen (SLA)) T lymphocytes. Finally, larger lesions were also correlated with a higher frequency of SLA specific inflammatory cytokine (IFN-gamma or TNF-alpha) producing lymphocytes. These studies demonstrate that immunological markers are correlated with clinical indicators of human leishmaniasis and serve to better understand the evolution of this important parasitic disease.

  1. The Dynamic Behavior of the Early Dental Caries Lesion in Caries-active Adults and Implications

    PubMed Central

    Brown, J P; Amaechi, B T; Bader, J D; Shugars, D; Vollmer, W M; Chen, C; Gilbert, G H; Esterberg, E J

    2015-01-01

    Objective To describe the full range of behavior of the visible, non-cavitated, early caries lesion in caries-active adults with substantial fluoride exposure, and to consider implications. Methods The data were from the Xylitol for Adult Caries Trial (X-ACT), collected annually for 33 months using condensed ICDAS caries threshold criteria. Individual tooth surfaces having a non-cavitated caries lesion were included and the Patterns of transition to each subsequent annual clinical examination to sound, non-cavitated or cavitated, filled or crowned were determined. The resulting sets of Patterns for an individual tooth surface, looking forward from its first appearance as a non-cavitated lesion, were combined into one of four behavior Profiles classified as Reversing, Stable, Oscillating or continuously Progressing, or were excluded if not part of the caries continuum. The distributions of Profile types were assessed using the Rao-Scott Chi square test, which adjusts for clustering of tooth surfaces within teeth. Results Inter-and intra-examiner Kappa scores demonstrated acceptable calibration at baseline and annually. 8084 tooth surfaces from 543 subjects were included. The distribution of Profile types differed significantly between coronal and root surfaces. Overall two-thirds of all coronal non-cavitated lesions were first seen at baseline, half Reversed, over a fifth were Stable, 15% Oscillated and only 8.3% progressed to cavitation, filled or crowned in 33 months or less. (6.3% consistently Progressed plus 2.0% inconsistently, a subset of Oscillating, which oscillated before progressing to cavitation). Approximal, smooth and occlusal coronal surfaces each were significantly different in their individual distributions of Profile types. Xylitol showed no significant and consistent effect on this distribution by tooth surface type. This was in keeping with the X-ACT Trial’s lack of effect of xylitol at the non-cavitated plus cavitated lesion thresholds combined

  2. Validity of a portable microhardness testing system (Cariotester) for diagnosis of progression in active caries lesions.

    PubMed

    Iwami, Yukiteru; Yamamoto, Hiroko; Hayashi, Mikako

    2013-01-01

    This study aimed to evaluate the validity of a portable microhardness testing system (Cariotester) for diagnosis of progression in active caries lesions by comparing data from this device and a laser fluorescence device (DIAGNOdent). Carious dentin in 12 specimens (stained clearly with a caries detector dye) was incrementally removed with a round bur at 150 μm depth intervals from the dentin surface in the direction of the pulp chamber. After each increment (total 138 sites), the Knoop hardness (HK) (evaluated with Cariotester) and DIAGNOdent (D) values were measured. HK values increased as D values decreased (regression formula: HK=0.419+238.342/D (p<0.001); coefficient of determination (R(2)): 0.602). Although DIAGNOdent quantitatively evaluates the degree of caries progression and bacterial infection status in caries lesions, our results demonstrate the validity and convenience of alternatively using microhardness measurements during caries removal to evaluate disease progression.

  3. Activation of nuclear factor kappa B pathway and reduction of hypothalamic oxytocin following hypothalamic lesions

    PubMed Central

    Roth, Christian L.; D’Ambrosio, Gabrielle; Elfers, Clinton

    2016-01-01

    Background Hypothalamic obesity (HO) occurs in patients with tumors and lesions in the medial hypothalamic region. In this study, a hyperphagic rat model of combined medial hypothalamic lesions (CMHL) was used to test which specific inflammatory molecules are involved. Methods In order to target specific homeostatic medial hypothalamic nuclei (arcuate, ventromedial, and dorsomedial nuclei), male Sprague-Dawley rats (age of 8 weeks, ~250 g body weight) received four electrolytic lesions or sham surgery. Post-surgery food intake and weight changes were tracked and hypothalamic gene expression for inflammatory molecules as well as anorexigenic peptide oxytocin 7 days and 7 months post-surgery were tested. Results Seven days post-surgery, average food intake increased by 23%, and body weight gain had increased by 68%. Toll-like 4 receptor/nuclear factor–κB (TLR4/NF–κB)—pathway was specifically activated in the mediobasal hypothalamus (MBH), resulting in 3-fold higher tumor necrosis factor (TNF)-α, 10-fold higher interleukin (IL) 1-β mRNA levels, and higher expression of suppression of cytokine signaling (SOCS) 3, while oxytocin mRNA levels were significantly reduced in CMHL rats versus sham surgery rats 7 days post-surgery. At 7 months, inflammation was less stimulated in MBH of CMHL rats compared to 7 days post-surgery and SOCS 3 as well as oxytocin mRNA levels were comparable between the two groups. Conclusion Medial hypothalamic lesions are associated with strong post-surgery hyperphagia and activation of TLR4/NF–κB—pathway as well as reduced expression of oxytocin in the hypothalamus. PMID:27512604

  4. The hyperactive syndrome: metanalysis of genetic alterations, pharmacological treatments and brain lesions which increase locomotor activity.

    PubMed

    Viggiano, Davide

    2008-12-01

    The large number of transgenic mice realized thus far with different purposes allows addressing new questions, such as which animals, over the entire set of transgenic animals, show a specific behavioural abnormality. In the present study, we have used a metanalytical approach to organize a database of genetic modifications, brain lesions and pharmacological interventions that increase locomotor activity in animal models. To further understand the resulting data set, we have organized a second database of the alterations (genetic, pharmacological or brain lesions) that reduce locomotor activity. Using this approach, we estimated that 1.56% of the genes in the genome yield to hyperactivity and 0.75% of genes produce hypoactivity when altered. These genes have been classified into genes for neurotransmitter systems, hormonal, metabolic systems, ion channels, structural proteins, transcription factors, second messengers and growth factors. Finally, two additional classes included animals with neurodegeneration and inner ear abnormalities. The analysis of the database revealed several unexpected findings. First, the genes that, when mutated, induce hyperactive behaviour do not pertain to a single neurotransmitter system. In fact, alterations in most neurotransmitter systems can give rise to a hyperactive phenotype. In contrast, fewer changes can decrease locomotor activity. Specifically, genetic and pharmacological alterations that enhance the dopamine, orexin, histamine, cannabinoids systems or that antagonize the cholinergic system induce an increase in locomotor activity. Similarly, imbalances in the two main neurotransmitters of the nervous system, GABA and glutamate usually result in hyperactive behaviour. It is remarkable that no genetic alterations pertaining to the GABA system have been reported to reduce locomotor behaviour. Other neurotransmitters, such as norepinephrine and serotonin, have a more complex influence. For instance, a decrease in norepinephrine

  5. A Platelet/CMC coupled with offline UPLC-QTOF-MS/MS for screening antiplatelet activity components from aqueous extract of Danshen.

    PubMed

    Chen, Ying; Zhang, Na; Ma, Jian; Zhu, Yan; Wang, Meng; Wang, Xiaoming; Zhang, Peng

    2016-01-01

    Platelets play crucial roles in thromboembolic and cardiovascular disease. The main platelets membrane receptors include adenosine diphosphate receptors, thrombin receptors, thromboxane prostanoid receptors and collagen receptors. In this study, a Platelet/CMC coupled with offline UPLC-QTOF-MS/MS system was built to screen antiplatelet activity components from aqueous extract of Danshen, which serve as an agent of antiplatelet aggregation in Traditional Chinese Medicine. Rosmarinic acid, lithospermic acid, salvianolic acid B, two isomers of salvianolic acid B, salvianolic acid C, salvianolic acid D and salvianolic acid H/I were identified as the potential antiplatelet activity components. Moreover, rosmarinic acid, lithospermic acid, salvianolic acid B, salvianolic acid C and danshensu were tested in platelet aggregation in vitro assay. The results suggested their retention time was closely related to the antiplatelet aggregation activities. This study provides a rapid, effective and novel method for screening the potential antiplatelet activity components from Chinese herb medicines.

  6. Sensorimotor semantics on the spot: brain activity dissociates between conceptual categories within 150 ms.

    PubMed

    Moseley, Rachel L; Pulvermüller, Friedemann; Shtyrov, Yury

    2013-01-01

    Although semantic processing has traditionally been associated with brain responses maximal at 350-400 ms, recent studies reported that words of different semantic types elicit topographically distinct brain responses substantially earlier, at 100-200 ms. These earlier responses have, however, been achieved using insufficiently precise source localisation techniques, therefore casting doubt on reported differences in brain generators. Here, we used high-density MEG-EEG recordings in combination with individual MRI images and state-of-the-art source reconstruction techniques to compare localised early activations elicited by words from different semantic categories in different cortical areas. Reliable neurophysiological word-category dissociations emerged bilaterally at ~ 150 ms, at which point action-related words most strongly activated frontocentral motor areas and visual object-words occipitotemporal cortex. These data now show that different cortical areas are activated rapidly by words with different meanings and that aspects of their category-specific semantics is reflected by dissociating neurophysiological sources in motor and visual brain systems.

  7. The impact of a parkinsonian lesion on dynamic striatal dopamine transmission depends on nicotinic receptor activation

    PubMed Central

    Jennings, Katie A.; Platt, Nicola J.; Cragg, Stephanie J.

    2015-01-01

    Dopamine function is disturbed in Parkinson's disease (PD), but whether and how release of dopamine from surviving neurons is altered has long been debated. Nicotinic acetylcholine receptors (nAChRs) on dopamine axons powerfully govern dopamine release and could be critical contributing factors. We revisited whether fundamental properties of dopamine transmission are changed in a parkinsonian brain and tested the potentially profound masking effects of nAChRs. Using real-time detection of dopamine in mouse striatum after a partial 6-hydroxydopamine lesion and under nAChR inhibition, we reveal that dopamine signals show diminished sensitivity to presynaptic activity. This effect manifested as diminished contrast between DA release evoked by the lowest versus highest frequencies. This reduced activity-dependence was underpinned by loss of short-term facilitation of dopamine release, consistent with an increase in release probability (Pr). With nAChRs active, the reduced activity-dependence of dopamine release after a parkinsonian lesion was masked. Consequently, moment-by-moment variation in activity of nAChRs may lead to dynamic co-variation in dopamine signal impairments in PD. PMID:26117304

  8. Local Inflammation, Dissemination and Coalescence of Lesions Are Key for the Progression toward Active Tuberculosis: The Bubble Model

    PubMed Central

    Prats, Clara; Vilaplana, Cristina; Valls, Joaquim; Marzo, Elena; Cardona, Pere-Joan; López, Daniel

    2016-01-01

    The evolution of a tuberculosis (TB) infection toward active disease is driven by a combination of factors mostly related to the host response. The equilibrium between control of the bacillary load and the pathology generated is crucial as regards preventing the growth and proliferation of TB lesions. In addition, some experimental evidence suggests an important role of both local endogenous reinfection and the coalescence of neighboring lesions. Herein we propose a mathematical model that captures the essence of these factors by defining three hypotheses: (i) lesions grow logistically due to the inflammatory reaction; (ii) new lesions can appear as a result of extracellular bacilli or infected macrophages that escape from older lesions; and (iii) lesions can merge when they are close enough. This model was implemented in Matlab to simulate the dynamics of several lesions in a 3D space. It was also fitted to available microscopy data from infected C3HeB/FeJ mice, an animal model of active TB that reacts against Mycobacterium tuberculosis with an exaggerated inflammatory response. The results of the simulations show the dynamics observed experimentally, namely an initial increase in the number of lesions followed by fluctuations, and an exponential increase in the mean area of the lesions. In addition, further analysis of experimental and simulation results show a strong coincidence of the area distributions of lesions at day 21, thereby highlighting the consistency of the model. Three simulation series removing each one of the hypothesis corroborate their essential role in the dynamics observed. These results demonstrate that three local factors, namely an exaggerated inflammatory response, an endogenous reinfection, and a coalescence of lesions, are needed in order to progress toward active TB. The failure of one of these factors stops induction of the disease. This mathematical model may be used as a basis for developing strategies to stop the progression of

  9. Positron emission mammography (PEM): Effect of activity concentration, object size, and object contrast on phantom lesion detection

    SciTech Connect

    MacDonald, Lawrence R.; Wang, Carolyn L.; Eissa, Marna; Haseley, David; Kelly, Mary M.; Liu, Franklin; Parikh, Jay R.; Beatty, J. David; Rogers, James V.

    2012-10-15

    Purpose: To characterize the relationship between lesion detection sensitivity and injected activity as a function of lesion size and contrast on the PEM (positron emission mammography) Flex Solo II scanner using phantom experiments. Methods: Phantom lesions (spheres 4, 8, 12, 16, and 20 mm diameter) were randomly located in uniform background. Sphere activity concentrations were 3 to 21 times the background activity concentration (BGc). BGc was a surrogate for injected activity; BGc ranged from 0.44-4.1 kBq/mL, corresponding to 46-400 MBq injections. Seven radiologists read 108 images containing zero, one, or two spheres. Readers used a 5-point confidence scale to score the presence of spheres. Results: Sensitivity was 100% for lesions {>=}12 mm under all conditions except for one 12 mm sphere with the lowest contrast and lowest BGc (60% sensitivity). Sensitivity was 100% for 8 mm spheres when either contrast or BGc was high, and 100% for 4 mm spheres only when both contrast and BGc were highest. Sphere contrast recovery coefficients (CRC) were 49%, 34%, 26%, 14%, and 2.8% for the largest to smallest spheres. Cumulative specificity was 98%. Conclusions: Phantom lesion detection sensitivity depends more on sphere size and contrast than on BGc. Detection sensitivity remained {>=}90% for injected activities as low as 100 MBq, for lesions {>=}8 mm. Low CRC in 4 mm objects results in moderate detection sensitivity even for 400 MBq injected activity, making it impractical to optimize injected activity for such lesions. Low CRC indicates that when lesions <8 mm are observed on PEM images they are highly tracer avid with greater potential of clinical significance. High specificity (98%) suggests that image statistical noise does not lead to false positive findings. These results apply to the 85 mm thick object used to obtain them; lesion detectability should be better (worse) for thinner (thicker) objects based on the reduced (increased) influence of photon attenuation.

  10. Sources of abnormal EEG activity in the presence of brain lesions.

    PubMed

    Fernández-Bouzas, A; Harmony, T; Bosch, J; Aubert, E; Fernández, T; Valdés, P; Silva, J; Marosi, E; Martínez-López, M; Casián, G

    1999-04-01

    In routine clinical EEG, a common origin is assumed for delta and theta rhythms produced by brain lesions. In previous papers, we have provided some experimental support, based on High Resolution qEEG and dipole fitting in the frequency domain, for the hypothesis that delta and theta spectral power have independent origins related to lesion and edema respectively. This paper describes the results obtained with Frequency Domain VARETA (FD-VARETA) in a group of 13 patients with cortical space-occupying lesions, in order to: 1) Test the accuracy of FD-VARETA for the localization of brain lesions, and 2) To provide further support for the independent origin of delta and theta components. FD VARETA is a distributed inverse solution, constrained by the Montreal Neurological Institute probabilistic atlas that estimates the spectra of EEG sources. In all patients, logarithmic transformed source spectra were compared with age-matched normative values, defining the Z source spectrum. Maximum Z values were found in 10 patients within the delta band (1.56 to 3.12 Hz); the spatial extent of these sources in the atlas corresponded with the location of the tumors in the CT. In 2 patients with small metastases and large volumes of edema and in a patient showing only edema, maximum Z values were found between 4.29 and 5.12 Hz. The spatial extent of the sources at these frequencies was within the volume of the edema in the CT. These results provided strong support to the hypothesis that both delta and theta abnormal EEG activities are the counterparts of two different pathophysiological processes. PMID:10358783

  11. GC-MS investigation and acetylcholinesterase inhibitory activity of Galanthus rizehensis.

    PubMed

    Sarikaya, Buket Bozkurt; Somer, Nehir Unver; Kaya, Gulen Irem; Onur, Mustafa Ali; Bastida, Jaume; Berkov, Strahil

    2013-01-01

    GC-MS (gas chromatography-mass spectrometry) analyses of alkaloids in the aerial parts and bulbs of Galanthus rizehensis Stern (Amaryllidaceae), collected during two different vegetation periods, was performed. Twenty three alkaloids were identified in four different alkaloid extracts. Acetylcholinesterase (AChE) inhibitory activities of the alkaloid extracts were tested. Both the highest alkaloid diversity and the most potent inhibitory activity (IC50 12.94 microg/ml) were obtained in extracts from the bulbs of G. rizehensis collected during the fruiting period.

  12. Measurement of O(6)-alkylguanine-DNA alkyltransferase activity in tumour cells using stable isotope dilution HPLC-ESI-MS/MS.

    PubMed

    Sun, Guohui; Zhao, Lijiao; Fan, Tengjiao; Ren, Ting; Zhong, Rugang

    2016-10-15

    The repair of DNA mediated by O(6)-alkylguanine-DNA alkyltransferase (AGT) provides protection against DNA damage from endogenous or exogenous alkylation of the O(6) position of guanine. However, this repair acts as a double-edged sword in cancer treatment, as it not only protects normal cells from chemotherapy-associated toxicities, but also results in cancer cell resistance to guanine O(6)-alkylating antitumour agents. Thus, AGT plays an important role in predicting the individual susceptibility to guanine O(6)-alkylating carcinogens and chemotherapies. Accordingly, it is necessary to establish a quantitative method for determining AGT activity with high accuracy, sensitivity and practicality. Here, we describe a novel nonradioactive method for measuring AGT activity using stable isotope dilution high-performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). This method is based on the irreversibility of the removal of the O(6)-alkyl group from guanine by AGT and on the high affinity of O(6)-benzylguanine (O(6)-BG) as an AGT substrate. HPLC-ESI-MS/MS was used to measure the AGT activities in cell protein extracts from eight tumour lines, demonstrating that AGT activity was quite variable among different cell lines, ranging from nondetectable to 1021 fmol/mg protein. The experiments performed in intact tumour cells yielded similar results but exhibited slightly higher activities than those observed in cell protein extracts. The accuracy of this method was confirmed by an examination of AGT expression levels using western blotting analysis. To our knowledge, this method is the first mass spectrometry-based AGT activity assay, and will likely provide assistance in the screening of cancer risk or the application of chemotherapies. PMID:27544051

  13. Measurement of O(6)-alkylguanine-DNA alkyltransferase activity in tumour cells using stable isotope dilution HPLC-ESI-MS/MS.

    PubMed

    Sun, Guohui; Zhao, Lijiao; Fan, Tengjiao; Ren, Ting; Zhong, Rugang

    2016-10-15

    The repair of DNA mediated by O(6)-alkylguanine-DNA alkyltransferase (AGT) provides protection against DNA damage from endogenous or exogenous alkylation of the O(6) position of guanine. However, this repair acts as a double-edged sword in cancer treatment, as it not only protects normal cells from chemotherapy-associated toxicities, but also results in cancer cell resistance to guanine O(6)-alkylating antitumour agents. Thus, AGT plays an important role in predicting the individual susceptibility to guanine O(6)-alkylating carcinogens and chemotherapies. Accordingly, it is necessary to establish a quantitative method for determining AGT activity with high accuracy, sensitivity and practicality. Here, we describe a novel nonradioactive method for measuring AGT activity using stable isotope dilution high-performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). This method is based on the irreversibility of the removal of the O(6)-alkyl group from guanine by AGT and on the high affinity of O(6)-benzylguanine (O(6)-BG) as an AGT substrate. HPLC-ESI-MS/MS was used to measure the AGT activities in cell protein extracts from eight tumour lines, demonstrating that AGT activity was quite variable among different cell lines, ranging from nondetectable to 1021 fmol/mg protein. The experiments performed in intact tumour cells yielded similar results but exhibited slightly higher activities than those observed in cell protein extracts. The accuracy of this method was confirmed by an examination of AGT expression levels using western blotting analysis. To our knowledge, this method is the first mass spectrometry-based AGT activity assay, and will likely provide assistance in the screening of cancer risk or the application of chemotherapies.

  14. Spectral embedding based active contour (SEAC): application to breast lesion segmentation on DCE-MRI

    NASA Astrophysics Data System (ADS)

    Agner, Shannon C.; Xu, Jun; Rosen, Mark; Karthigeyan, Sudha; Englander, Sarah; Madabhushi, Anant

    2011-03-01

    Spectral embedding (SE), a graph-based manifold learning method, has previously been shown to be useful in high dimensional data classification. In this work, we present a novel SE based active contour (SEAC) segmentation scheme and demonstrate its applications in lesion segmentation on breast dynamic contrast enhance magnetic resonance imaging (DCE-MRI). In this work, we employ SE on DCE-MRI on a per voxel basis to embed the high dimensional time series intensity vector into a reduced dimensional space, where the reduced embedding space is characterized by the principal eigenvectors. The orthogonal eigenvector-based data representation allows for computation of strong tensor gradients in the spectrally embedded space and also yields improved region statistics that serve as optimal stopping criteria for SEAC. We demonstrate both analytically and empirically that the tensor gradients in the spectrally embedded space are stronger than the corresponding gradients in the original grayscale intensity space. On a total of 50 breast DCE-MRI studies, SEAC yielded a mean absolute difference (MAD) of 3.2+/-2.1 pixels and mean Dice similarity coefficient (DSC) of 0.74+/-0.13 compared to manual ground truth segmentation. An active contour in conjunction with fuzzy c-means (FCM+AC), a commonly used segmentation method for breast DCE-MRI, produced a corresponding MAD of 7.2+/-7.4 pixels and mean DSC of 0.58+/-0.32. In conjunction with a set of 6 quantitative morphological features automatically extracted from the SEAC derived lesion boundary, a support vector machine (SVM) classifier yielded an area under the curve (AUC) of 0.73, for discriminating between 10 benign and 30 malignant lesions; the corresponding SVM classifier with the FCM+AC derived morphological features yielded an AUC of 0.65.

  15. UPLC-Q-TOF-MS analysis of non-volatile migrants from new active packaging materials.

    PubMed

    Aznar, M; Rodriguez-Lafuente, A; Alfaro, P; Nerin, C

    2012-10-01

    Ultra-performance liquid chromatography (UPLC) coupled to mass spectrometry (MS) is a useful tool in the analysis of non-volatile compounds, and the use of a quadrupole-time-of-flight (Q-TOF) mass analyzer allows a high sensitivity and accuracy when acquiring full fragment mode, providing a high assurance of correct identification of unknown compounds. In this work, UPLC-Q-TOF-MS technology has been applied to the analysis of non-volatile migrants from new active packaging materials. The materials tested were based on polypropylene (PP), ethylene-vinyl alcohol copolymer (EVOH), and poly(ethylene terephthalate) (PET). The active packaging materials studied were one PP film containing a natural antioxidant, and two PP/EVOH films, two PET/EVOH films and one coextruded PP/EVOH/PP film containing natural antimicrobials. The chemical structure of several compounds was unequivocally identified. The analysis revealed the migration of some of the active substances used in the manufacture of active packaging, such as caffeine (0.07 ± 0.01 μg/g), carvacrol (0.31 ± 0.03 μg/g) and citral (0.20 ± 0.01 μg/g). Unintentionally added substances were also found, such as citral reaction compounds, or citral impurities present in the raw materials. PMID:22836481

  16. Comprehensive Proteomic Study of the Antiproliferative Activity of a Polyphenol-Enriched Rosemary Extract on Colon Cancer Cells Using Nanoliquid Chromatography-Orbitrap MS/MS.

    PubMed

    Valdés, Alberto; Artemenko, Konstantin A; Bergquist, Jonas; García-Cañas, Virginia; Cifuentes, Alejandro

    2016-06-01

    In this work, a proteomics strategy based on nanoliquid chromatography-tandem mass spectrometry (nano-LC-MS/MS) using an Orbitrap high-resolution mass spectrometer together with stable isotope dimethyl labeling (DML) is applied to quantitatively examine relative changes in the protein fraction of HT-29 human colon cancer cells treated with different concentrations of a polyphenol-enriched rosemary extract over the time. The major objective of this study was to gain insights into the antiproliferative mechanisms induced by rosemary polyphenols. Using this methodology, 1909 and 698 proteins were identified and quantified in cell extracts. The polyphenol-enriched rosemary extract treatment changed the expression of several proteins in a time- and concentration-dependent manner. Most of the altered proteins are implicated in the activation of Nrf2 transcription factor and the unfolded protein response. In conclusion, rosemary polyphenols induced proteomic changes that were related to the attenuation of aggresome formation and activation of autophagy to alleviate cellular stress.

  17. A new background distribution-based active contour model for three-dimensional lesion segmentation in breast DCE-MRI

    SciTech Connect

    Liu, Hui; Liu, Yiping; Qiu, Tianshuang; Zhao, Zuowei; Zhang, Lina

    2014-08-15

    Purpose: To develop and evaluate a computerized semiautomatic segmentation method for accurate extraction of three-dimensional lesions from dynamic contrast-enhanced magnetic resonance images (DCE-MRIs) of the breast. Methods: The authors propose a new background distribution-based active contour model using level set (BDACMLS) to segment lesions in breast DCE-MRIs. The method starts with manual selection of a region of interest (ROI) that contains the entire lesion in a single slice where the lesion is enhanced. Then the lesion volume from the volume data of interest, which is captured automatically, is separated. The core idea of BDACMLS is a new signed pressure function which is based solely on the intensity distribution combined with pathophysiological basis. To compare the algorithm results, two experienced radiologists delineated all lesions jointly to obtain the ground truth. In addition, results generated by other different methods based on level set (LS) are also compared with the authors’ method. Finally, the performance of the proposed method is evaluated by several region-based metrics such as the overlap ratio. Results: Forty-two studies with 46 lesions that contain 29 benign and 17 malignant lesions are evaluated. The dataset includes various typical pathologies of the breast such as invasive ductal carcinoma, ductal carcinomain situ, scar carcinoma, phyllodes tumor, breast cysts, fibroadenoma, etc. The overlap ratio for BDACMLS with respect to manual segmentation is 79.55% ± 12.60% (mean ± s.d.). Conclusions: A new active contour model method has been developed and shown to successfully segment breast DCE-MRI three-dimensional lesions. The results from this model correspond more closely to manual segmentation, solve the weak-edge-passed problem, and improve the robustness in segmenting different lesions.

  18. Identification and Simultaneous Determination of Twelve Active Components in the Methanol Extract of Traditional Medicine Weichang’an Pill by HPLC-DAD-ESI-MS/MS

    PubMed Central

    Zhang, Jingze; Gao, Wenyuan; Liu, Zhen; Zhang, Zhidan

    2013-01-01

    Weichang’an (WCA) pill, a traditional Chinese patent medicine consisting of ten Chinese medicinal herbs, has been used to treat irritable bowel syndrome and functional dyspepsia for several decades. In this study, twelve bioactive constituents in the methanol extract of WCA were accurately identified since MS/MS fragmentation behavior of the references and the standards by using HPLC-DAD-ESI-MS/MS analysis and a reliable and accurate method for the simultaneous determination was developed. Twelve active components including costunolide and dehydrodehydrocostus lactone from the principal herb Radix Aucklandiae; naringin, hesperidin and neohesperidin from Fructus Aurantii; magnolol and honokiol from the ministerial herbs Cortex Magnoliae officinalis; aloe-emodin, rhein, emodin, chrysophanol and physcion from adjunctive and messenger herb Radix et Rhizoma Rhei were analyzed in the samples. The chromatographic separation was performed on a Kromasil C18 column with gradient elution of acetonitrile-methanol and 1.0% acetic acid water. In this condition, linearity, inter- and intra-day precision and accuracy were within acceptable ranges. The developed method showed satisfactory precision and accuracy with overall intra- and inter-day variations of 0.68-1.33% and 0.67-2.05% respectively, and the overall recoveries of 97.54-102.69% for twelve compounds. The proposed approach was successfully applied as a powerful tool for the quality control of WCA pill. PMID:24250567

  19. Application of ion trap-MS with H/D exchange and QqTOF-MS in the identification of microbial degradates of trimethoprim in nitrifying activated sludge.

    PubMed

    Eichhorn, Peter; Ferguson, P Lee; Pérez, Sandra; Aga, Diana S

    2005-07-01

    In this work, the identification of two microbial degradation products of the antimicrobial trimethoprim (290 Da) is described. The structural elucidation of the metabolites, which were produced by nitrifying activated sludge bacteria in a small-scale laboratory batch reactor, was accomplished by electrospray ionization-ion trap mass spectrometry conducting consecutive fragmentation steps (MS(n)) combined with H/D-exchange experiments. Although one metabolite corresponded to alpha-hydroxytrimethoprim (306 Da), oxidation of the aromatic ring within the diaminopyrimidine substructure was determined for the second degradate (324 Da). Accurate mass measurements of the two metabolites were provided by a hybrid quadrupole time-of-flight-mass spectrometer operated in MS/MS mode. With absolute mass errors of <5 mDa, it allowed us to confirm the proposed elemental composition for the protonated precursor ions as well as for a series of fragment ions that were previously identified by ion trap mass spectrometry. The study emphasized the potential of nitrifying activated sludge bacteria for breaking down an environmentally relevant pharmaceutical that is otherwise poorly degradable by a bacterial community encountered in conventional activated sludge.

  20. Quantitation of Alpha-Glucosidase Activity Using Fluorinated Carbohydrate Array and MALDI-TOF-MS.

    PubMed

    Yang, Hyojik; Chan, Allen L; LaVallo, Vincent; Cheng, Quan

    2016-02-01

    Quantitation of alpha-glucosidase (α-GD) activity is of significance to diagnosis of many diseases including Pompe disease and type II diabetes. We report here a new method to determine α-GD activity using matrix-assisted laser desorption/ionization (MALDI)-time-of-flight (TOF) mass spectrometry (MS) in combination with carbohydrate microarray and affinity surface chemistry. Carbohydrate probes are synthesized for capture of the enzymatic reaction products and the adducts are loaded onto a fluorinated gold surface to generate an array, which is followed by characterization by MALDI-TOF-MS. The ratio of intensities is used to determine the level of activity of several enzymes. In addition, half maximal inhibitory concentration (IC50) of acarbose and epigallocatechin gallate are also determined using this approach, and the results agree well with the reported values. This method is advantageous as compared to conventional colorimetric techniques that typically suffer matrix interference problems from samples. The use of the polyfluorinated surface has effectively suppressed the interference. PMID:26760440

  1. Lesions Arising in a Tattoo of an Active Duty US Marine Corps Woman.

    PubMed

    Winn, Aubrey E; Rivard, Shayna C; Green, Brian

    2016-01-01

    Tattoos are ubiquitous in modern society; however, they do not come without risk of medical complications. When complications arise in the military community, a particularly thorough differential diagnosis should be considered based on the increased exposures service members have during deployment and throughout their military career. We present a case of a 38-year-old active duty US Marine Corps woman with worsening skin lesions arising within a tattoo 6 weeks after acquiring the tattoo on her right chest. Given environmental exposures from a recent deployment to the Middle East, a wide differential was considered. Ultimately, a skin biopsy revealed early hypertrophic scar formation responsive to therapy with intralesional triamcinolone acetonide (Kenalog® [ILK]). However, given the Marine had recently deployed and is part of the active duty population, consideration of alternative, albeit rare, etiologies was imperative. PMID:27450611

  2. Antioxidant activities and phenolics profiling of different parts of Carica papaya by LCMS-MS.

    PubMed

    Zunjar, V; Mammen, D; Trivedi, B M

    2015-01-01

    This article deals with the comparison of the antioxidant activity of aqueous extracts of various parts of Carica papaya L. The evaluation of total phenolic content and total flavonoid content revealed high antioxidant potential of the seeds and fruits. The free radical-scavenging potential of the aqueous extracts indicated the seeds to have better DPPH-scavenging activity than fruits. The results were augmented by the FRAP activity as well. The phenolics present in the extracts were separated and identified as 5-hydroxy feruloyl quinic acid, acetyl p-coumaryl quinic acid, quercetin-3-O-rhamnoside, syringic acid hexoside, 5-hydroxy caffeic quinic acid, peonidin-3-O-glucoside, sinapic acid-O-hexoside, cyaniding-3-O-glucose and methyl feruloyl glycoside by LCMS-MS technique.

  3. Tuning the hydrogen evolution activity of MS2 (M = Mo or Nb) monolayers by strain engineering.

    PubMed

    Chen, Xiaobo; Wang, Guangjin

    2016-04-14

    Strain engineering is an effective strategy to tune the electronic, magnetic and optical properties of atomically thin materials like graphene and monolayer transition-metal dichalcogenides (m-TMDs). Using first-principles calculations, we show that strain is also effective for tuning the catalytic activity of m-MS2 (M = Mo or Nb) towards the hydrogen evolution reaction (HER), which is essential for electrochemical hydrogen generation from water splitting. A wide strain range covering both compressive (0-6%) and tensile (0-10%) regions is considered. It is found that biaxial tensile strain can enhance the HER activity more effectively than uniaxial tensile strain, while compressive strain deteriorates the HER activity. Compared with monolayer 1T-NbS2, monolayers 1T-MoS2 and 1H-NbS2 exhibit better strain tunability towards their HER activities since more active sites can be induced with increasing strain. In contrast, monolayer 1H-MoS2 is catalytically inert in the considered strain range because H adsorption is too weak. We demonstrate that tensile strain can lead to decrease of the adiabatic proton affinity but simultaneously a larger magnitude of increase of the adiabatic electron affinity, thus enhancing the catalytic activity. Electronic structure calculations show that tensile strain can activate the relatively inert inner valence electrons and enlarge the d-band exchange splitting, both of which induce destabilization of the system and enhancement of catalytic activity. PMID:26878108

  4. α-Glucosidase inhibition and antioxidant activity of an oenological commercial tannin. Extraction, fractionation and analysis by HPLC/ESI-MS/MS and (1)H NMR.

    PubMed

    Muccilli, Vera; Cardullo, Nunzio; Spatafora, Carmela; Cunsolo, Vincenzo; Tringali, Corrado

    2017-01-15

    Two batches of the oenological tannin Tan'Activ R, (toasted oak wood - Quercus robur), were extracted with ethanol. A fractionation on XAD-16 afforded four fractions for each extract. Extracts and fractions were evaluated for antioxidant activity (DPPH), polyphenol content (GAE) and yeast α-glucosidase inhibitory activity. Comparable results were obtained for both columns, fractions X1B and X2B showing the highest antioxidant activity. Fractions X1C and X2C notably inhibited α-glucosidase, with IC50=9.89 and 8.05μg/mL, respectively. Fractions were subjected to HPLC/ESI-MS/MS and (1)H NMR analysis. The main phenolic constituents of both X1B and X2B were a monogalloylglucose isomer (1), a HHDP-glucose isomer (2), castalin (3) gallic acid (4), vescalagin (5), and grandinin (or its isomer roburin E, 6). X1C and X2C showed a complex composition, including non-phenolic constituents. Fractionation of X2C gave a subfraction, with enhanced α-glucosidase inhibitory activity (IC50=6.15μg/mL), with castalagin (7) as the main constituent. PMID:27542449

  5. HPLC-ESI-IT-MS/MS Analysis and Biological Activity of Triterpene Glycosides from the Colombian Marine Sponge Ectyoplasia ferox

    PubMed Central

    Colorado-Ríos, Jhonny; Muñoz, Diana; Montoya, Guillermo; Márquez, Diana; Márquez, Maria-Elena; López, Juan; Martínez, Alejandro

    2013-01-01

    The marine sponge Ectyoplasia ferox produces antipredatory and allelopathic triterpenoid glycosides as part of its chemical defense repertoire against predators, competitors, and fouling organisms. These molecules are responsible for the pharmacological potential found in the glycosides present in this species. In order to observe the glycochemical diversity present in E. ferox, a liquid chromatography coupled to a tandem mass spectrometry approach to analyse a complex polar fraction of this marine sponge was performed. This gave valuable information for about twenty-five compounds three of which have been previously reported and another three which were found to be composed of known aglycones. Furthermore, a group of four urabosides, sharing two uncommon substitutions with carboxyl groups at C-4 on the terpenoid core, were identified by a characteristic fragmentation pattern. The oxidized aglycones present in this group of saponins can promote instability, making the purification process difficult. Cytotoxicity, cell cycle modulation, a cell cloning efficiency assay, as well as its hemolytic activity were evaluated. The cytotoxic activity was about IC50 40 µg/mL on Jurkat and CHO-k1 cell lines without exhibiting hemolysis. Discussion on this bioactivity suggests the scanning of other biological models would be worthwhile. PMID:24317472

  6. Example based lesion segmentation

    NASA Astrophysics Data System (ADS)

    Roy, Snehashis; He, Qing; Carass, Aaron; Jog, Amod; Cuzzocreo, Jennifer L.; Reich, Daniel S.; Prince, Jerry; Pham, Dzung

    2014-03-01

    Automatic and accurate detection of white matter lesions is a significant step toward understanding the progression of many diseases, like Alzheimer's disease or multiple sclerosis. Multi-modal MR images are often used to segment T2 white matter lesions that can represent regions of demyelination or ischemia. Some automated lesion segmentation methods describe the lesion intensities using generative models, and then classify the lesions with some combination of heuristics and cost minimization. In contrast, we propose a patch-based method, in which lesions are found using examples from an atlas containing multi-modal MR images and corresponding manual delineations of lesions. Patches from subject MR images are matched to patches from the atlas and lesion memberships are found based on patch similarity weights. We experiment on 43 subjects with MS, whose scans show various levels of lesion-load. We demonstrate significant improvement in Dice coefficient and total lesion volume compared to a state of the art model-based lesion segmentation method, indicating more accurate delineation of lesions.

  7. Example Based Lesion Segmentation

    PubMed Central

    Roy, Snehashis; He, Qing; Carass, Aaron; Jog, Amod; Cuzzocreo, Jennifer L.; Reich, Daniel S.; Prince, Jerry; Pham, Dzung

    2016-01-01

    Automatic and accurate detection of white matter lesions is a significant step toward understanding the progression of many diseases, like Alzheimer’s disease or multiple sclerosis. Multi-modal MR images are often used to segment T2 white matter lesions that can represent regions of demyelination or ischemia. Some automated lesion segmentation methods describe the lesion intensities using generative models, and then classify the lesions with some combination of heuristics and cost minimization. In contrast, we propose a patch-based method, in which lesions are found using examples from an atlas containing multi-modal MR images and corresponding manual delineations of lesions. Patches from subject MR images are matched to patches from the atlas and lesion memberships are found based on patch similarity weights. We experiment on 43 subjects with MS, whose scans show various levels of lesion-load. We demonstrate significant improvement in Dice coefficient and total lesion volume compared to a state of the art model-based lesion segmentation method, indicating more accurate delineation of lesions.

  8. Trace analysis of polar pharmaceuticals in wastewater by LC-MS-MS: comparison of membrane bioreactor and activated sludge systems.

    PubMed

    Celiz, Mary Dawn; Pérez, Sandra; Barceló, Damià; Aga, Diana S

    2009-01-01

    In order to assess the efficiency of wastewater treatment plants in removing pharmaceuticals from wastewater, sensitive and reliable methods are necessary for trace analysis of these micropollutants in the presence of a highly complex matrix. In this study, conventional activated sludge (CAS) and membrane bioreactor (MBR) treatment systems are compared in eliminating pharmaceuticals in wastewater. The pharmaceuticals investigated include aceclofenac, carbamazepine, diclofenac, enalapril, and trimethoprim. Analysis is performed using a liquid chromatograph with hybrid linear ion-trap mass spectrometer equipped with a polar reversed-phase column to achieve good separation and minimize matrix effects. To pre-concentrate the samples, the use of two types of solid-phase extraction packing materials in tandem assures good recoveries of all the target analytes. In the influent, the concentration of these compounds ranges from 0.09 to 1.4 microg/L. Diclofenac shows resistance to degradation in the CAS but is amenable to degradation in the MBR. Trimethoprim and enalapril are only slightly eliminated in the CAS but are reduced by more than 95% in the MBR. Carbamazepine removal is negligible, while aceclofenac is only 50% reduced in CAS and MBR. In general, these results indicate that MBR has a higher efficiency in removing some polar pharmaceuticals in wastewater.

  9. STS-55 MS1/PLC Ross monitors Payload Specialist Walter's Anthrorack activity

    NASA Technical Reports Server (NTRS)

    1993-01-01

    STS-55 German Payload Specialist 1 Ulrich Walter breathes into Rack 9 Anthrorack (AR) (Human Physiology Laboratory) device for Pulmonary Perfusion and Ventilation During Rest and Exercise experiment while working inside the Spacelab Deutsche 2 (SL-D2) science module aboard the Earth-orbiting Columbia, Orbiter Vehicle (OV) 102. Seated on the bicycle ergometer, Walter utilizes the respiratory monitoring system, part of a broad battery of experiments designed to investigate human physiology under microgravity conditions. In the background, Mission Specialist 1 (MS1) and Payload Commander (PLC) Jerry L. Ross monitors Walter's activity. Walter represents the German Aerospace Research Establishment (DLR) on the 10-day SL-D2 mission. Visible on the aft end cone are a fire extinguisher and the Crew Telesupport Experiment (CTE) Macintosh portable computer mounted on an adjustable work platform.

  10. Effect of MS-153, a glutamate transporter activator, on the conditioned rewarding effects of morphine, methamphetamine and cocaine in mice.

    PubMed

    Nakagawa, Takayuki; Fujio, Mayumi; Ozawa, Tohru; Minami, Masabumi; Satoh, Masamichi

    2005-01-30

    There is a body of evidence implying the involvement of the glutamatergic system in the conditioned rewarding effects of drugs of abuse. It is recognized that the release of extracellular glutamate from nerve terminals is counterbalanced by the functions of neuronal and glial glutamate transporters. In the present study, we investigated the effects of (R)-(-)-5-methyl-1-nicotinoyl-2-pyrazoline (MS-153), a glutamate transporter activator, on the induction of the conditioned place preference to morphine, methamphetamine and cocaine in mice. In the conditioned place preference paradigm, mice were conditioned with repeated subcutaneous injections of morphine (5 mg/kg), methamphetamine (2 mg/kg) or cocaine (8 mg/kg) in combination with or without MS-153 (3 and 10 mg/kg). Co-administration of MS-153 at a dose of 10 mg/kg, but not 3 mg/kg, significantly attenuated the induction of conditioned place preference to morphine, methamphetamine and cocaine. However, MS-153 itself produced neither conditioned place preference nor aversion. On the other hand, co-administration of MS-153 (10 mg/kg) did not alter the acute locomotor activation elicited by a single injection of morphine, methamphetamine and cocaine. These results suggest that MS-153, a glutamate transporter activator, has an inhibitory effect on the conditioned rewarding effects of morphine, methamphetamine and cocaine without affecting their acute locomotor responses.

  11. Comparable reduction in Zif268 levels and cytochrome oxidase activity in the retrosplenial cortex following mammillothalamic tract lesions.

    PubMed

    Frizzati, Aura; Milczarek, Michal M; Sengpiel, Frank; Thomas, Kerrie L; Dillingham, Christopher M; Vann, Seralynne D

    2016-08-25

    Damage to the mammillothalamic tract (MTT) produces memory impairments in both humans and rats, yet it is still not clear why this diencephalic pathway is vital for memory. One suggestion is that it is an important route for midbrain inputs to reach a wider cortical and subcortical network that supports memory. Consistent with this idea, MTT lesions produce widespread hypoactivity in distal brain regions as measured by the immediate-early gene, c-fos. To determine whether these findings were selective to c-fos or reflected more general changes in neuronal function, we assessed the effects of MTT lesions on the expression of the immediate-early gene protein, Zif268 and the metabolic marker, cytochrome oxidase, in the retrosplenial cortex and hippocampus. The lesions decreased levels of both activity markers in the superficial and deep layers of the retrosplenial cortex in both its granular and dysgranular subregions. In contrast, no significant changes were observed in the hippocampus, despite the MTT-lesioned animals showing marked impairments on T-maze alternation. These findings are consistent with MTT lesions providing important, indirect inputs for normal retrosplenial cortex functioning. These distal functional changes may contribute to the memory impairments observed after MTT lesions. PMID:27233617

  12. Spondias tuberosa (Anacardiaceae) leaves: profiling phenolic compounds by HPLC-DAD and LC-MS/MS and in vivo anti-inflammatory activity.

    PubMed

    da Silva Siqueira, Emerson Michell; Félix-Silva, Juliana; de Araújo, Lorena Maria Lima; Fernandes, Julia Morais; Cabral, Bárbara; Gomes, Jacyra Antunes Dos Santos; de Araújo Roque, Alan; Tomaz, José Carlos; Lopes, Norberto Peporine; de Freitas Fernandes-Pedrosa, Matheus; Giordani, Raquel Brandt; Zucolotto, Silvana Maria

    2016-10-01

    Spondias tuberosa is a medicinal plant used by several local communities in northeast Brazil to treat infections, digestive disorders and inflammatory conditions. The study aimed to identify and quantify the major phenolic in hydroethanolic extract of leaves from S. tuberosa and to evaluate its anti-inflammatory potential. The chemical profile of extract was analyzed by HPLC-DAD and HPLC-MS. The in vivo anti-inflammatory activity was investigated in carrageenan-induced hind paw edema and peritonitis models in mice. Identified and quantified through HPLC-DAD or HPLC-MS analyses of S. tuberosa extract were the following compounds: chlorogenic acid, caffeic acid, rutin and isoquercitrin. The inflammatory response to carrageenan was significantly reduced in both models by S. tuberosa extract. In hind paw edema, the edematogenic response was reduced by up to 63.6% and the myeloperoxidase activity was completely inhibited. In the peritonitis model, the total cell migration into the peritoneal cavity was reduced by up to 65%. The results obtained give evidence of the anti-inflammatory action of S. tuberosa and suggest the potential therapeutic benefit of this plant on inflammatory conditions. The chlorogenic acid, caffeic acid, rutin and isoquercitrin identified and quantified in S. tuberosa leaves enable us to suggest that these compounds could be used as chemical markers for quality control of derivative products from this species. Copyright © 2016 John Wiley & Sons, Ltd.

  13. Comprehensive Proteomic Study of the Antiproliferative Activity of a Polyphenol-Enriched Rosemary Extract on Colon Cancer Cells Using Nanoliquid Chromatography-Orbitrap MS/MS.

    PubMed

    Valdés, Alberto; Artemenko, Konstantin A; Bergquist, Jonas; García-Cañas, Virginia; Cifuentes, Alejandro

    2016-06-01

    In this work, a proteomics strategy based on nanoliquid chromatography-tandem mass spectrometry (nano-LC-MS/MS) using an Orbitrap high-resolution mass spectrometer together with stable isotope dimethyl labeling (DML) is applied to quantitatively examine relative changes in the protein fraction of HT-29 human colon cancer cells treated with different concentrations of a polyphenol-enriched rosemary extract over the time. The major objective of this study was to gain insights into the antiproliferative mechanisms induced by rosemary polyphenols. Using this methodology, 1909 and 698 proteins were identified and quantified in cell extracts. The polyphenol-enriched rosemary extract treatment changed the expression of several proteins in a time- and concentration-dependent manner. Most of the altered proteins are implicated in the activation of Nrf2 transcription factor and the unfolded protein response. In conclusion, rosemary polyphenols induced proteomic changes that were related to the attenuation of aggresome formation and activation of autophagy to alleviate cellular stress. PMID:27103343

  14. Identification of proteins associated with ligand-activated estrogen receptor α in human breast cancer cell nuclei by tandem affinity purification and nano LC-MS/MS.

    PubMed

    Tarallo, Roberta; Bamundo, Angela; Nassa, Giovanni; Nola, Ernesto; Paris, Ornella; Ambrosino, Concetta; Facchiano, Angelo; Baumann, Marc; Nyman, Tuula A; Weisz, Alessandro

    2011-01-01

    Estrogen receptor α (ER-α) is a key mediator of estrogen actions in breast cancer (BC) cells. Understanding the effects of ligand-activated ER-α in target cells requires identification of the molecular partners acting in concert with this nuclear receptor to transduce the hormonal signal. We applied tandem affinity purification (TAP), glycerol gradient centrifugation and MS analysis to isolate and identify proteins interacting with ligand-activated ER-α in MCF-7 cell nuclei. This led to the identification of 264 ER-associated proteins, whose functions highlight the hinge role of ER-α in the coordination of multiple hormone-regulated nuclear processes in BC cells. PMID:21182205

  15. Constitutive activation of p38 MAPK in tumor cells contributes to osteolytic bone lesions in multiple myeloma.

    PubMed

    Yang, J; He, J; Wang, J; Cao, Y; Ling, J; Qian, J; Lu, Y; Li, H; Zheng, Y; Lan, Y; Hong, S; Matthews, J; Starbuck, M W; Navone, N M; Orlowski, R Z; Lin, P; Kwak, L W; Yi, Q

    2012-09-01

    Bone destruction is a hallmark of multiple myeloma and affects more than 80% of patients. However, current therapy is unable to completely cure and/or prevent bone lesions. Although it is accepted that myeloma cells mediate bone destruction by inhibition of osteoblasts and activation of osteoclasts, the underlying mechanism is still poorly understood. This study demonstrates that constitutive activation of p38 mitogen-activated protein kinase in myeloma cells is responsible for myeloma-induced osteolysis. Our results show that p38 is constitutively activated in most myeloma cell lines and primary myeloma cells from patients. Myeloma cells with high/detectable p38 activity, but not those with low/undetectable p38 activity, injected into severe combined immunodeficient (SCID) or SCID-hu mice caused bone destruction. Inhibition or knockdown of p38 in human myeloma reduced or prevented myeloma-induced osteolytic bone lesions without affecting tumor growth, survival, or homing to bone. Mechanistic studies showed that myeloma cell p38 activity inhibited osteoblastogenesis and bone formation and activated osteoclastogenesis and bone resorption in myeloma-bearing SCID mice. This study elucidates a novel molecular mechanism-activation of p38 signaling in myeloma cells-by which myeloma cells induce osteolytic bone lesions, and indicates that targeting myeloma cell p38 may be a viable approach to treating or preventing myeloma bone disease. PMID:22425892

  16. Roles of BN52021 in platelet-activating factor pathway in inflammatory MS1 cells

    PubMed Central

    Xia, Shi-Hai; Xiang, Xiao-Hui; Chen, Kai; Xu, Wei

    2013-01-01

    AIM: To determine the effects of BN52021 on platelet-activating factor receptor (PAFR) signaling molecules under lipopolysaccharide (LPS)-induced inflammatory conditions in MS1 cells. METHODS: MS1 cells (a mouse pancreatic islet endothelial cell line) were grown in Dulbecco’s modified Eagle’s medium supplemented with 10% fetal bovine serum, 2 mmol/L glutamine and 100 μg/mL penicillin/streptomycin in 5% CO2 at 37 °C. After growth to confluency in media, the cells were processed for subsequent studies. The MS1 cells received 0, 0.1, 1 and 10 μg/mL LPS in this experiment. The viability/proliferation of the cells induced by LPS was observed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay. Apoptosis and necrosis of the cells under the inflammatory condition described previously were observed using Hoechst 33342-propidium iodide staining. Adenylate cyclase (AC), phospholipase A2 (PLA2), phospholipase Cβ (PLCβ), protein tyrosine kinase (PTK), G protein-coupled receptor kinases (GRK) and p38-mitogen-activated protein kinase (p38 MAPK) mRNA in the PAFR signaling pathway were measured by real-time polymerase chain reaction. The protein expression level of phosphorylated AC (p-AC), phosphorylated PLA2 (p-PLA2), phosphorylated PTK (p-PTK), phosphorylated p38 MAPK (p-p38 MAPK), PLCβ and GRK was measured using Western blotting analysis. RESULTS: The activity of MS1 cells incubated with different concentrations of LPS for 6 h decreased significantly in the 1 μg/mL LPS group (0.49 ± 0.10 vs 0.67 ± 0.13, P < 0.05) and 10 μg/mL LPS group (0.44 ± 0.10 vs 0.67 ± 0.13, P < 0.001), but not in 0.1 μg/mL group. When the incubation time was extended to 12 h (0.33 ± 0.05, 0.32 ± 0.03 and 0.25 ± 0.03 vs 0.69 ± 0.01) and 24 h (0.31 ± 0.01, 0.29 ± 0.03 and 0.25 ± 0.01 vs 0.63 ± 0.01), MS1 cell activity decreased in all LPS concentration groups compared with the blank control (P < 0.001). BN52021 significantly improved the cell

  17. Chemical Profiling Using Uplc Q-Tof/Ms and Antioxidant Activities of Fortunella Fruits.

    PubMed

    Tan, Si; Zhao, Xijuan; Yang, Ying; Ke, Zunli; Zhou, Zhiqin

    2016-07-01

    The fruits of Fortunella Swingle are widely consumed as fresh fruits and traditional medicine in China. China is the origin center and has the largest cultivated area of the genus Fortunella. In this study, the chemical compositions of ethanol extracts of the major Fortunella cultivated types including Fortunella japonica Swingle, Fortunella margarita Swingle, Fortunella crassifolia Swingle 1 (Lanshang) and Fortunella crassifolia Swingle 2 (Liuyang) were determined using ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC Q-TOF/MS) method, and their antioxidant activities were evaluated. 12 compounds were identified and 5 compounds were tentatively characterized. The results showed that the chemical compositions of the ethanol extracts of 4 Fortunella cultivated types were largely the same. 3', 5'-di-C-glucopyranosylphloretin was the predominant flavonoid in Fortunella fruits, and Fortunella margarita Swingle had higher contents of flavonoids than other species. In addition, the data demonstrated high antioxidant activities of Fortunella fruits. The developed method could be available to rapidly analyze the chemical compounds in Fortunella fruits and its products. This study will provide information for further quality assessment and utilization of Fortunella resources. PMID:27243926

  18. An HPLC-MS/MS method for simultaneous determination of the active metabolites of febuxostat (67M-1, 67M-2 and 67M-4) in human plasma.

    PubMed

    Xie, Huiru; Wang, Zhijun; Deng, Ke; Jiang, Xuehua; Wang, Ling; Lv, Guoyu

    2014-11-01

    An HPLC-MS/MS method for simultaneously determination of the active metabolites (67M-1, 67M-2 and 67M-4) in human plasma using clopidogrel as the internal standard was developed and validated. The compounds were extracted by protein precipitation using acetonitrile and separated using a C8 column by a gradient elution with the mobile phase consisting of acetonitrile (containing 0.1% formic acid) and 0.1% formic acid. Quantification was performed using multiple reaction monitoring in positive mode with m/z transitions of 333.1-261.0, 333.1-261.0, 347.0-261.0 and 322.2-184.1 for 67M-1, 67M-2, 67M-4 and clopidogrel (Internal Standard), respectively. This method was validated in terms of specificity, linearity, precision, accuracy, and stability. The lower limit of quantification of this method was 0.5 ng/mL and the calibration curve was linear over the concentration range of 0.5-150 ng/mL. The intra- and inter-run precision was less than 11.67% and 8.64%, respectively, with the accuracy between 98.33% and 108.38%. The samples were stable under all the tested conditions. This method has been successfully applied to the pharmacokinetic study of febuxostat in healthy Chinese volunteers following oral administration of 40 mg and 80 mg febuxostat.

  19. Epigenetic Activation of Antibacterial Property of an Endophytic Streptomyces coelicolor Strain AZRA 37 and Identification of the Induced Protein Using MALDI TOF MS/MS.

    PubMed

    Kumar, Jitendra; Sharma, Vijay K; Singh, Dheeraj K; Mishra, Ashish; Gond, Surendra K; Verma, Satish K; Kumar, Anuj; Kharwar, Ravindra Nath

    2016-01-01

    The endophytic Streptomyces coelicolor strain AZRA 37 was isolated from the surface sterilized root of Azadirachta indica A. Juss., commonly known as neem plant in India. Since only a few reports are available regarding epigenetic modulations of microbial entities, S. coelicolor was treated with different concentrations of 5-azacytidine for this purpose and evaluated for its antibacterial potential against five human pathogenic bacteria (Aeromonas hydrophila IMS/GN11, Enterococcus faecalis IMS/GN7, Salmonella typhi MTCC 3216, Shigella flexneri ATCC 12022 and Staphylococcus aureus ATCC 25923). The crude extract obtained from cultures treated with 25 μM concentration of 5-azacytidine, was found effective against all five pathogenic bacteria tested while the untreated control was only active against 3 pathogenic bacteria. HPLC analysis of crude compounds from treated cultures showed a greater number of compounds than that of the control. Extraction of whole cell protein and its SDS PAGE analysis showed an additional major protein band in 25 μM 5-azacytidine treated culture and MALDI TOF MS/MS analysis revealed that this protein belongs to the porin family. PMID:26844762

  20. LC-MS/MS assay for the determination of lurasidone and its active metabolite, ID-14283 in human plasma and its application to a clinical pharmacokinetic study.

    PubMed

    Katteboina, Mahitej Yadav; Pilli, Nageswara Rao; Mullangi, Ramesh; Seelam, Raghunadha Reddy; Satla, Shobha Rani

    2016-07-01

    The authors proposed a sensitive, selective and rapid liquid chromatography-tandem mass spectrometric (LC-MS/MS) assay procedure for the quantification of lurasidone and its active metabolite, i.e. ID-14283 in human plasma simultaneously using corresponding isotope labeled compounds as internal standards as per regulatory guidelines. After liquid-liquid extraction with tert-butyl methyl ether, the analytes were chromatographed on a C18 column using an optimized mobile phase composed of 5 mm ammonium acetate (pH 5.0) and acetonitrile (15:85, v/v) and delivered at a flow rate of 1.00 mL/min. The assay exhibits excellent linearity in the concentration ranges of 0.25-100 and 0.10-14.1 ng/mL for lurasidone and ID-14283, respectively. The precision and accuracy results over five concentration levels in four different batches were well within the acceptance limits. Lurasidone and ID-14283 were found to be stable in battery of stability studies. The method was rapid with the chromatographic run time 2.5 min, which made it possible to analyze 300 samples in a single day. Additionally, this method was successfully used to estimate the in vivo plasma concentrations of lurasidone and ID-14283 obtained from a pharmacokinetic study in south Indian male subjects and the results were authenticated by conducting incurred samples reanalysis. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26577488

  1. Epigenetic Activation of Antibacterial Property of an Endophytic Streptomyces coelicolor Strain AZRA 37 and Identification of the Induced Protein Using MALDI TOF MS/MS

    PubMed Central

    Kumar, Jitendra; Sharma, Vijay K.; Singh, Dheeraj K.; Mishra, Ashish; Gond, Surendra K.; Verma, Satish K.; Kumar, Anuj; Kharwar, Ravindra Nath

    2016-01-01

    The endophytic Streptomyces coelicolor strain AZRA 37 was isolated from the surface sterilized root of Azadirachta indica A. Juss., commonly known as neem plant in India. Since only a few reports are available regarding epigenetic modulations of microbial entities, S. coelicolor was treated with different concentrations of 5-azacytidine for this purpose and evaluated for its antibacterial potential against five human pathogenic bacteria (Aeromonas hydrophila IMS/GN11, Enterococcus faecalis IMS/GN7, Salmonella typhi MTCC 3216, Shigella flexneri ATCC 12022 and Staphylococcus aureus ATCC 25923). The crude extract obtained from cultures treated with 25 μM concentration of 5-azacytidine, was found effective against all five pathogenic bacteria tested while the untreated control was only active against 3 pathogenic bacteria. HPLC analysis of crude compounds from treated cultures showed a greater number of compounds than that of the control. Extraction of whole cell protein and its SDS PAGE analysis showed an additional major protein band in 25 μM 5-azacytidine treated culture and MALDI TOF MS/MS analysis revealed that this protein belongs to the porin family. PMID:26844762

  2. The radial diffusivity and magnetization transfer pool size ratio are sensitive markers for demyelination in a rat model of type III multiple sclerosis (MS) lesions

    PubMed Central

    Janve, Vaibhav A.; Zu, Zhongliang; Yao, Song-Yi; Li, Ke; Zhang, Fang Lin; Wilson, Kevin; Ou, Xiawei; Does, Mark D.; Subramaniam, Sriram; Gochberg, Daniel F.

    2013-01-01

    Determining biophysical sensitivity and specificity of quantitative magnetic resonance imaging is essential to develop effective imaging metrics of neurodegeneration. Among these metrics apparent pool size ratio (PSR) from quantitative magnetization transfer (qMT) imaging and radial diffusivity (RD) from diffusion tensor imaging (DTI) are both known to relate to histological measure of myelin density and integrity. However their relative sensitivities towards quantitative myelin detection are unknown. In this study, we correlated high-resolution quantitative magnetic resonance imaging measures of subvoxel tissue structures with corresponding quantitative myelin histology in a lipopolysacharide (LPS) mediated animal model of MS. Specifically, we acquired quantitative magnetization transfer (qMT) and diffusion tensor imaging (DTI) metrics (on the same tissue sample) in an animal model system of type III oligodendrogliopathy which lacked prominent lymphocytic infiltration, a system that had not been previously examined with quantitative MRI. We find that the qMT measured apparent pool size ratio (PSR) showed the strongest correlation with a histological measure of myelin content. DTI measured RD showed the next strongest correlation, and other DTI and relaxation parameters (such as the longitudinal relaxation rate (R1f) or fractional anisotropy (FA)) showed considerably weaker correlations with myelin content. PMID:23481461

  3. Pediatric MS

    MedlinePlus

    ... of the oral medications in the pediatric population. Network of Pediatric MS Centers The National MS Society ... MS Study Group (2004) and established a nationwide network of six Pediatric MS Centers of Excellence (2006) ...

  4. Constitutive activation of p38 MAPK in tumor cells contributes to osteolytic bone lesions in multiple myeloma

    PubMed Central

    Yang, Jing; He, Jin; Wang, Ji; Cao, Yabing; Ling, Jianhua; Qian, Jianfei; Lu, Yong; Li, Haiyan; Zheng, Yuhuan; Lan, Yongsheng; Hong, Sungyoul; Matthews, Jairo; Starbuck, Michael W; Navone, Nora M; Orlowski, Robert Z.; Lin, Pei; Kwak, Larry W.; Yi, Qing

    2012-01-01

    Bone destruction is a hallmark of multiple myeloma and affects more than 80% of patients. However, current therapy is unable to completely cure and/or prevent bone lesions. Although it is accepted that myeloma cells mediate bone destruction by inhibition of osteoblasts and activation of osteoclasts, the underlying mechanism is still poorly understood. This study demonstrates that constitutive activation of p38 mitogen-activated protein kinase in myeloma cells is responsible for myeloma-induced osteolysis. Our results show that p38 is constitutively activated in most myeloma cell lines and primary myeloma cells from patients. Myeloma cells with high/detectable p38 activity, but not those with low/undetectable p38 activity, injected into SCID or SCID-hu mice caused bone destruction. Inhibition or knockdown of p38 in human myeloma reduced or prevented myeloma-induced osteolytic bone lesions without affecting tumor growth, survival, or homing to bone. Mechanistic studies showed that myeloma cell p38 activity inhibited osteoblastogenesis and bone formation and activated osteoclastogenesis and bone resorption in myeloma-bearing SCID mice. This study elucidates a novel molecular mechanism—sactivation of p38 signaling in myeloma cells—by which myeloma cells induce osteolytic bone lesions and indicates that targeting myeloma cell p38 may be a viable approach to treating or preventing myeloma bone disease. PMID:22425892

  5. Combination of MS protein identification and bioassay of chromatographic fractions to identify biologically active substances from complex protein sources.

    PubMed

    Kuromitsu, Sadao; Yokota, Hiroyuki; Hiramoto, Masashi; Yuri, Masatoshi; Naitou, Masanori; Nakamura, Naoto; Kawabata, Shigeki; Kobori, Masato; Katoh, Masao; Furuchi, Kiyoshi; Mita, Haruhisa; Yamada, Tetsuo

    2009-06-01

    Purification of biologically active proteins from complex biological sources is a difficult task, usually requiring large amounts of sample and many separation steps. We found an active substance in a serum response element-dependent luciferase reporter gene bioassay in interstitial cystitis urine that we attempted to purify with column chromatography and the bioassay. With anion-exchange Mono Q and C4 reversed-phase columns, apparently sharp active peaks were obtained. However, more than 20 kinds of proteins were identified from the active fractions with MS, indicating that the purification was not complete. As further purification was difficult, we chose a candidate molecule by means of studying the correlation between MS protein identification scores and bioassay responses of chromatographic fractions near the active peaks. As a result, epidermal growth factor (EGF) was nominated as a candidate molecule among the identified proteins because the elution profile of EGF was consistent with that of the bioassay, and the correlation coefficient of EGF between MS protein identification scores and bioassay responses was the highest among all the identified proteins. With recombinant EGF and anti-EGF and anti-EGF receptor antibodies, EGF was confirmed to be the desired substance in interstitial cystitis urine. This approach required only 20 ml of urine sample and two column chromatographic steps. The combination of MS protein identification and bioassay of chromatographic fractions may be useful for identifying biologically active substances from complex protein sources.

  6. The hippocampus and appetitive Pavlovian conditioning: effects of excitotoxic hippocampal lesions on conditioned locomotor activity and autoshaping.

    PubMed

    Ito, Rutsuko; Everitt, Barry J; Robbins, Trevor W

    2005-01-01

    The hippocampus (HPC) is known to be critically involved in the formation of associations between contextual/spatial stimuli and behaviorally significant events, playing a pivotal role in learning and memory. However, increasing evidence indicates that the HPC is also essential for more basic motivational processes. The amygdala, by contrast, is important for learning about the motivational significance of discrete cues. This study investigated the effects of excitotoxic lesions of the rat HPC and the basolateral amygdala (BLA) on the acquisition of a number of appetitive behaviors known to be dependent on the formation of Pavlovian associations between a reward (food) and discrete stimuli or contexts: (1) conditioned/anticipatory locomotor activity to food delivered in a specific context and (2) autoshaping, where rats learn to show conditioned discriminated approach to a discrete visual CS+. While BLA lesions had minimal effects on conditioned locomotor activity, hippocampal lesions facilitated the development of both conditioned activity to food and autoshaping behavior, suggesting that hippocampal lesions may have increased the incentive motivational properties of food and associated conditioned stimuli, consistent with the hypothesis that the HPC is involved in inhibitory processes in appetitive conditioning.

  7. Early Activation of Th2/Th22 Inflammatory and Pruritogenic Pathways in Acute Canine Atopic Dermatitis Skin Lesions.

    PubMed

    Olivry, Thierry; Mayhew, David; Paps, Judy S; Linder, Keith E; Peredo, Carlos; Rajpal, Deepak; Hofland, Hans; Cote-Sierra, Javier

    2016-10-01

    Determining inflammation and itch pathway activation in patients with atopic dermatitis (AD) is fraught with the inability to precisely assess the age of skin lesions, thus affecting the analysis of time-dependent mediators. To characterize inflammatory events occurring during early experimental acute AD lesions, biopsy samples were collected 6, 24, and 48 hours after epicutaneous application of Dermatophagoides farinae house dust mites to sensitized atopic dogs. The skin transcriptome was assessed using a dog-specific microarray and quantitative PCR. Acute canine AD skin lesions had a significant up-regulation of genes encoding T helper (Th) 2 (e.g., IL4, IL5, IL13, IL31, and IL33), Th9 (IL9), and Th22 (IL22) cytokines as well as Th2-promoting chemokines such as CCL5 and CCL17. Proinflammatory (e.g., IL6, LTB, and IL18) cytokines were also up-regulated. Other known pruritogenic pathways were also activated: there was significant up-regulation of genes encoding proteases cathepsin S (CTSS), mast cell chymase (CMA1), tryptase (TPS1) and mastin, neuromedin-B (NMB), nerve growth factor (NGF), and leukotriene-synthesis enzymes (ALOX5, ALOX5AP, and LTA4H). Experimental acute canine house dust mite-induced AD lesions exhibit an activation of innate and adaptive immune responses and pruritogenic pathways similar to those seen in humans with acute AD, thereby validating this model to test innovative therapeutics modalities for this disease.

  8. Are Neutrophil Extracellular Traps Playing a Role in the Parasite Control in Active American Tegumentary Leishmaniasis Lesions?

    PubMed Central

    Morgado, Fernanda Nazaré; Nascimento, Michelle T. C.; Saraiva, Elvira M.; de Oliveira-Ribeiro, Carla; Madeira, Maria de Fátima; da Costa-Santos, Marcela; Vasconcellos, Erica C. F.; F. Pimentel, Maria Ines; Rosandiski Lyra, Marcelo; Schubach, Armando de Oliveira; Conceição-Silva, Fátima

    2015-01-01

    Neutrophil extracellular traps (NETs) have been described as a network of extracellular fibers composed by DNA, histones and various proteins/enzymes. Studies have demonstrated that NETs could be responsible for the trapping and elimination of a variety of infectious agents. In order to verify the presence of NETs in American tegumentary leishmaniasis (ATL) and their relationship with the presence of amastigotes we evaluated active cutaneous lesions of 35 patients before treatment by the detection of parasites, neutrophils (neutrophil elastase) and histones through immunohistochemistry and confocal immunofluorescence. Intact neutrophils could be detected in all ATL lesions. NETs were present in 27 patients (median 1.1; range from 0.1 to 23.5/mm2) with lesion duration ranging from one to seven months. NETs were in close proximity with neutrophils (r = 0.586; p = 0.0001) and amastigotes (r = 0.710; p = 0.0001). Two patterns of NET formation were detected: small homogeneously distributed networks observed in all lesions; and large structures that could be visualized at a lower magnification in lesions presenting at least 20% of neutrophils. Lesions presenting the larger NET formation showed high parasite detection. A correlation between NET size and the number of intact amastigotes was observed (p=0.02). As we detected an association between NET and amastigotes, our results suggest that neutrophil migration and NET formation could be stimulated and maintained by stimuli derived from the parasite burden/parasite antigen in the extracellular environment. The observation of areas containing only antigens not intermingled with NETs (elastase and histone) suggests that the involvement of these structures in the control of parasite burden is a dynamic process in which the formation of NETs is exhausted with the destruction of the parasites. Since NETs were also associated with granulomas, this trapping would favor the activity of macrophages in order to control the parasite

  9. Inhibitive activities detection of monoamine oxidases (MAO) A and B inhibitors in human liver MAO incubations by UPLC-ESI-MS/MS.

    PubMed

    Jiang, Bo; Li, Shuping; Liu, Wei; Yang, Yadi; Chen, Wenxia; He, Dandan; Cheng, Xuemei; Wang, Zhengtao; Chen, Wansheng; Wang, Changhong

    2015-11-10

    A sensitive UPLC-ESI-MS/MS method was developed for determining and screening of inhibitors of monoamine oxidase (MAO) by using mix MAO enzymes prepared from human liver. 5-Hydroxytryptamine (5-HT) and 2-phenethylamine (2-PEA) were used as substrates for MAO-A and MAO-B in incubations, and 5-hydroxyindole-3-acetic acid (5-HIAA) and phenylacetic acid (PAA) resulting from 5-HT and 2-PEA were used as markers to evaluate inhibitive activities of test compounds on MAO-A and MAO-B. Proper separation was achieved for positive multiple reaction monitoring of 5-HIAA (m/z 192.1→146.1) and negative multiple reaction monitoring PAA (m/z 135.0→91.0) via isocratic elution (0.1% fromic acid:acetonitrile=60:40) on a HSS T3 column following a simple precipitation of proteins for sample treatment. The relative standard deviations of intra- and inter-day precisions were ranged from 1.74% to 6.76% and 0.77% to 9.35%. The mean accuracies for the quality control samples were 101.37±6.60% and 101.39±2.85%, respectively. This method exhibited characteristics of small total reaction volume (100μl), short analysis time (3.5min), highly sensitivity, low cost and without matrix effect (103.56±2.33% to 112.63±8.57% for 5-HIAA and 105.68±8.75% to 112.76±4.67% for PAA). The developed method was successfully applied for detection of the MAO-A and MAO-B inhibitive activities by model drugs, including pargyline, clorgyline, as well as β-carboline alkaloids from Peganum harmala.

  10. Levodopa replacement therapy alters enzyme activities in striatum and neuropeptide content in striatal output regions of 6-hydroxydopamine lesioned rats.

    PubMed

    Engber, T M; Susel, Z; Kuo, S; Gerfen, C R; Chase, T N

    1991-06-21

    The effects of striatal dopamine denervation and levodopa replacement therapy on neuronal populations in the rat striatum were assessed by measurement of glutamic acid decarboxylase (GAD) and choline acetyltransferase (CAT) activities in the striatum, dynorphin and substance P concentrations in the substantia nigra, and enkephalin concentration in the globus pallidus. Rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal pathway were treated for 21 days with levodopa (100 mg/kg/day, i.p., with 25 mg/kg benserazide) on either an intermittent (b.i.d.) or continuous (osmotic pump infusion) regimen and sacrificed following a three day drug washout. In saline-treated control rats, striatal GAD activity and globus pallidus enkephalin content were elevated and nigral substance P content was reduced ipsilateral to the 6-OHDA lesion. Intermittent levodopa treatment further increased GAD activity, decreased CAT activity, restored substance P to control levels, markedly increased dynorphin content, and had no effect on enkephalin. In contrast, continuous levodopa elevated globus pallidus enkephalin beyond the levels occurring with denervation, but had no effect on any of the other neurochemical measures. These results indicate that striatal neuronal populations are differentially affected by chronic levodopa therapy and by the continuous or intermittent nature of the treatment regimen. With the exception of substance P, levodopa did not reverse the effects of the 6-OHDA lesion but, rather, either exacerbated the lesion-induced changes (e.g. GAD and enkephalin) or altered neurochemical markers which had been unaffected by the lesion (e.g. CAT and dynorphin).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1717109

  11. In vitro nematicidal activity of aryl hydrazones and comparative GC-MS metabolomics analysis.

    PubMed

    Eloh, Kodjo; Demurtas, Monica; Deplano, Alessandro; Ngoutane Mfopa, Alvine; Murgia, Antonio; Maxia, Andrea; Onnis, Valentina; Caboni, Pierluigi

    2015-11-18

    A series of aryl hydrazones were synthesized and in vitro assayed for their activity on the root-knot nematode Meloidogyne incognita. The phenylhydrazones of thiophene-2-carboxyaldehyde 5, 3-methyl-2-thiophenecarboxyaldehyde, 6, and salicylaldehyde, 2, were the most potent with EC50/48h values of 16.6 ± 2.2, 23.2 ± 2.7, and 24.3 ± 1.4 mg/L, respectively. A GC-MS metabolomics analysis, after in vitro nematode treatment with hydrazone 6 at 100 mg/L for 12 h, revealed elevated levels of fatty acids such as lauric acid, stearic acid, 2-octenoic acid, and palmitic acid. Whereas control samples showed the highest levels of monoacylglycerols such as monostearin and 2-monostearin, surprisingly, 2 h after treatment with hydrazone 6, nematodes excreted 3 times the levels of ammonia eliminated in the same conditions by controls. Thus, phenylhydrazones may represent a good scaffold in the discovery and synthesis of new nematicidal compounds, and a metabolomics approach may be helpful in understanding their mechanisms of toxicity and mode of action. PMID:26528945

  12. 77 FR 28569 - Foreign-Trade Zone 92-Gulfport, MS Notification of Proposed Production Activity; Gulf Ship, LLC...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-15

    ...; Gulf Ship, LLC, (Shipbuilding), Gulfport, MS The Mississippi Coast Foreign-Trade Zone, Inc., grantee of FTZ 92, submitted a notification of proposed production activity on behalf of Gulf Ship, LLC (Gulf Ship), located in Gulfport, Mississippi. The Gulf Ship facility is located within Site 3 of FTZ 92....

  13. A solid-phase microextraction GC/MS/MS method for rapid quantitative analysis of food and beverages for the presence of legally restricted biologically active flavorings.

    PubMed

    Bousova, Katerina; Mittendorf, Klaus; Senyuva, Hamide

    2011-01-01

    A method was developed using automated headspace solid-phase microextraction coupled with GC/MS/MS to simultaneously determine the presence of seven biologically active flavoring substances whose levels of use in processed foods is controlled by statutory limits. The method can be applied to identify and quantify the presence of 1,2-benzopyrone (coumarin), beta-asarone, 1-allyl-4-methoxybenzene (estragole), menthofuran, 4-allyl-1 ,2-dimethoxybenzene (methyl eugenol), pulegone, and thujone at levels ranging from 0.5 to 3000 mg/kg. The method has been optimized and validated for three different generic food types categorized on the basis of composition and anticipated use levels of flavorings and food ingredients. The food categories are alcoholic and nonalcoholic beverages; semisolid processed foods (e.g., soups, sauces, confectionary, etc.); and solid foods (muesli, bakery products, etc.). The method is simple, inexpensive, and rapid, and eliminates the use of flammable and toxic solvents. There is no sample preparation, and using MSIMS, unequivocal confirmation of identification is achieved even in highly complex matrixes containing many potential interfering volatiles. The method precision for spiked samples ranged from 2 to 21%, with the greatest variability associated with solid matrixes. The LOD and LOQ values were well below 0.1 and 0.5 mg/kg, respectively, in all cases for individual substances, fulfilling requirements for enforcement purposes. The robustness of the method was demonstrated in a small survey of retail samples of four spirits, five flavored milks, three energy drinks, five liqueurs, five soups, 10 sauces, five herbal teas, and three breakfast cereals. PMID:21919351

  14. A Top-Down LC-FTICR MS-Based Strategy for Characterizing Oxidized Calmodulin in Activated Macrophages

    SciTech Connect

    Lourette, Natacha M.; Smallwood, Heather S.; Wu, Si; Robinson, Errol W.; Squier, Thomas C.; Smith, Richard D.; Pasa-Tolic, Ljiljana

    2010-06-01

    Liquid chromatography-mass spectrometry (LC-MS) based approach for monitoring time dependent changes in the degree of nitration and oxidation of intact calmodulin (CaM) has been used to resolve approximately 500 CaM oxiforms. Tentative identifications of posttranslational modifications (PTMs) such as oxidation or nitration have been assigned by combining tryptic peptide information (generated from bottom-up analyses) with online collision induced dissociation (CID) tandem mass spectrometry (MS/MS) at the intact protein level. The reduction in abundance and diversity of oxidatively modified CaM (i.e. nitrated tyrosines and oxidized methionines) induced by macrophage activation has been explored and semi-quantified for different oxidation degrees of CaM (i.e. no oxidation, moderate and high oxidation). This work demonstrates the power of top-down approach to identify hundreds of combinations of posttranslational modifications (PTMs) for single protein target such as CaM.

  15. Quantitative, real-time analysis of base excision repair activity in cell lysates utilizing lesion-specific molecular beacons.

    PubMed

    Svilar, David; Vens, Conchita; Sobol, Robert W

    2012-01-01

    We describe a method for the quantitative, real-time measurement of DNA glycosylase and AP endonuclease activities in cell nuclear lysates using base excision repair (BER) molecular beacons. The substrate (beacon) is comprised of a deoxyoligonucleotide containing a single base lesion with a 6-Carboxyfluorescein (6-FAM) moiety conjugated to the 5'end and a Dabcyl moiety conjugated to the 3' end of the oligonucleotide. The BER molecular beacon is 43 bases in length and the sequence is designed to promote the formation of a stem-loop structure with 13 nucleotides in the loop and 15 base pairs in the stem. When folded in this configuration the 6-FAM moiety is quenched by Dabcyl in a non-fluorescent manner via Förster Resonance Energy Transfer (FRET). The lesion is positioned such that following base lesion removal and strand scission the remaining 5 base oligonucleotide containing the 6-FAM moiety is released from the stem. Release and detachment from the quencher (Dabcyl) results in an increase of fluorescence that is proportionate to the level of DNA repair. By collecting multiple reads of the fluorescence values, real-time assessment of BER activity is possible. The use of standard quantitative real-time PCR instruments allows the simultaneous analysis of numerous samples. The design of these BER molecular beacons, with a single base lesion, is amenable to kinetic analyses, BER quantification and inhibitor validation and is adaptable for quantification of DNA Repair activity in tissue and tumor cell lysates or with purified proteins. The analysis of BER activity in tumor lysates or tissue aspirates using these molecular beacons may be applicable to functional biomarker measurements. Further, the analysis of BER activity with purified proteins using this quantitative assay provides a rapid, high-throughput method for the discovery and validation of BER inhibitors.

  16. Breast Cancer Cells Induce Osteolytic Bone Lesions In vivo through a Reduction in Osteoblast Activity in Mice

    PubMed Central

    Gregory, Laura S.; Choi, Wilson; Burke, Leslie; Clements, Judith A.

    2013-01-01

    Bone metastases are severely debilitating and have a significant impact on the quality of life of women with metastatic breast cancer. Treatment options are limited and in order to develop more targeted therapies, improved understanding of the complex mechanisms that lead to bone lesion development are warranted. Interestingly, whilst prostate-derived bone metastases are characterised by mixed or osteoblastic lesions, breast-derived bone metastases are characterised by osteolytic lesions, suggesting unique regulatory patterns. This study aimed to measure the changes in bone formation and bone resorption activity at two time-points (18 and 36 days) during development of the bone lesion following intratibial injection of MDA-MB-231 human breast cancer cells into the left tibiae of Severely Combined Immuno-Deficient (SCID) mice. The contralateral tibia was used as a control. Tibiae were extracted and processed for undecalcified histomorphometric analysis. We provide evidence that the early bone loss observed following exposure to MDA-MB-231 cells was due to a significant reduction in mineral apposition rate, rather than increased levels of bone resorption. This suggests that osteoblast activity was impaired in the presence of breast cancer cells, contrary to previous reports of osteoclast-dependent bone loss. Furthermore mRNA expression of Dickkopf Homolog 1 (DKK-1) and Noggin were confirmed in the MDA-MB-231 cell line, both of which antagonise osteoblast regulatory pathways. The observed bone loss following injection of cancer cells was due to an overall thinning of the trabecular bone struts rather than perforation of the bone tissue matrix (as measured by trabecular width and trabecular separation, respectively), suggesting an opportunity to reverse the cancer-induced bone changes. These novel insights into the mechanisms through which osteolytic bone lesions develop may be important in the development of new treatment strategies for metastatic breast cancer

  17. Determination of 7alpha-OH cholesterol by LC-MS/MS: Application in assessing the activity of CYP7A1 in cholestatic minipigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An LC-MS/MS method was developed and validated to determine 7alpha-OH cholesterol in liver microsome. This method was convenient and fast with high specificity and sensitivity. Briefly, a gradient elution was performed on a Synergi polar-C18 column (50 x 4.6mm i.d., 3microm). The mobile phase (cons...

  18. Comparison Between Biofilm Production, Phospholipase and Haemolytic Activity of Different Species of Candida Isolated from Dental Caries Lesions in Children

    PubMed Central

    Shenoy, Neetha

    2016-01-01

    Introduction C.albicans is the most commonly isolated fungal pathogen in the oral cavity, but isolation of non-albicans Candida is increasing in recent years. We wish to demonstrate the virulence factors of Candida spp. isolated from the dental caries lesion of the children as presence of virulence factors determines the pathogenic potential of any microorganism. Aim To compare biofilm production, phospholipase and haemolytic activity of C.albicans with that of non-albicans species of Candida isolated from dental caries lesions of children to evaluate the role of non- albicans species of Candida in formation of dental caries. Materials and Methods Oral swabs were collected from caries lesion of 100 school children of age 5-10 years with dental caries. Candida isolates were tested for biofilm production, phospholipase and haemolytic activity. Statistical analysis was done by Chi-Square test and Mann-Whitney U test wherever applicable using SPSS version 11.5. Results Out of the 100 children with dental caries 37 were positive for Candida by smear or culture and 31 by culture. C.albicans was the most prevalent isolate followed by C.krusei, C.tropicalis and C.albicans. Out of 21 C.albicans isolates, 10 (47.6%) showed phospholipase activity and 18 (85.71%) produced biofilm. Of the 10 non-albicans strains, 5 (50%) showed phospholipase activity and 6 (60%) produced biofilm. All isolates of Candida produced haemolysin (100%). Conclusion There was no statistically relevant difference between the virulence factor production by C.albicans and non-albicans species of Candida. In other words, our study shows that both C.albicans and non-albicans species of Candida isolated from caries lesions of the children, produce these virulence factors. So we can say that non-albicans species of Candida also are involved in caries formation. PMID:27190803

  19. A pilot study examining functional brain activity 6 months after memory retraining in MS: the MEMREHAB trial.

    PubMed

    Dobryakova, Ekaterina; Wylie, Glenn R; DeLuca, John; Chiaravalloti, Nancy D

    2014-09-01

    Cognitive impairment in individuals with multiple sclerosis (MS) is now well recognized. One of the most common cognitive deficits is found in memory functioning, largely due to impaired acquisition. We examined functional brain activity 6 months after memory retraining in individuals with MS. The current report presents long term follow-up results from a randomized clinical trial on a memory rehabilitation protocol known as the modified Story Memory Technique. Behavioral memory performance and brain activity of all participants were evaluated at baseline, immediately after treatment, and 6 months after treatment. Results revealed that previously observed increases in patterns of cerebral activation during learning immediately after memory training were maintained 6 months post training.

  20. Early increase in DcR2 expression and late activation of caspases in the platelet storage lesion.

    PubMed

    Plenchette, S; Moutet, M; Benguella, M; N'Gondara, J P; Guigner, F; Coffe, C; Corcos, L; Bettaieb, A; Solary, E

    2001-10-01

    Platelet transfusion is widely used to prevent bleeding in patients with severe thrombocytopenia. The maximal storage duration of platelet concentrates is usually 5 days, due to the platelet storage lesion that impairs their functions when stored for longer times. Some of the morphological and biochemical changes that characterize this storage lesion are reminiscent of cell death by apoptosis. The present study analyzed whether proteins involved in nucleated cell apoptosis could play a role in the platelet storage lesion. Storage of leukocyte-depleted platelets obtained by apheresis is associated with a late and limited activation of caspases, mainly caspase-3. This event correlates with an increased expression of the pro-apoptotic BH3-only protein Bim in the particulate fraction and a slight and late release of the pro-apoptotic mitochondrial protein Diablo/Smac in the cytosol. Platelets do not express the death receptors Fas, DR4 and DR5 on their plasma membrane, while the expression of the decoy receptor DcR2 increases progressively during platelet storage. Addition of low concentrations of the cryoprotector dimethylsulfoxide accelerates platelet caspase activation during storage, an effect that is partially prevented by the caspase inhibitor z-VAD-fmk. Altogether, DcR2 expression on the plasma membrane is an early event while caspase activation is a late event during platelet storage. These observations suggest that caspases are unlikely to account for the platelet storage lesion. As a consequence, addition of caspase inhibitors may not improve the quality of platelet concentrates stored in standard conditions. PMID:11587215

  1. Rapid detection of carbapenemase activity: benefits and weaknesses of MALDI-TOF MS.

    PubMed

    Mirande, C; Canard, I; Buffet Croix Blanche, S; Charrier, J-P; van Belkum, A; Welker, M; Chatellier, S

    2015-11-01

    Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) has been introduced as an identification procedure for bacteria and fungi. The MALDI-TOF MS-based analysis of resistance to β-lactam antibiotics has been applied to detect hydrolysis of carbapenems by different bacterial strains. However, the detection of enzymatic carbapenem degradation by MALDI-TOF MS lacks well-standardized protocols and several methods and models of interpretation using different calculations of ratio-of-peak intensities have been described in the literature. Here, we used faropenem and ertapenem hydrolysis as model compounds. In an attempt to propose a universal protocol, the hydrolysis was regularly monitored during 24 h using well-characterized bacterial strains producing different types of carbapenemases (KPC, IMP, NDM, VIM, and OXA-48). Variable responses and different timing for detectable hydrolysis, depending on the enzyme produced, were observed. KPC degrades its template antibiotics very quickly (15 min for some KPC producers) compared to other types of enzymes (more than 90 min for other enzymes). Prior bacterial lysis was shown to be of no interest in the modulation or optimization of the hydrolytic kinetics. The adequate detection of carbapenem hydrolysis would, therefore, require several MALDI-TOF MS readouts for the timely detection of rapid hydrolysis without missing slow hydrolysis. This enzymatic constraint limits the implementation of a standard protocol in routine microbiology laboratories. PMID:26337432

  2. Increased metalloprotease activity in the epileptogenic lesion--Lobectomy reduces metalloprotease activity and urokinase-type uPAR circulating levels.

    PubMed

    Quirico-Santos, Thereza; Nascimento Mello, Angélica; Casimiro Gomes, Aline; de Carvalho, Lian Pontes; de Souza, Jorge Marcondes; Alves-Leon, Soniza

    2013-11-13

    Inflammation influences the pathogenesis of seizures by boosting neuronal degeneration of temporal lobe epilepsy with hippocampal sclerosis (TLE-HS). This work aimed to determine the activity of metalloproteases (MMPs) in brain tissue fragments of TLE-HS patients and the effect of lobectomy on circulating inflammatory biomarkers. Surgical fragments (n=4) from epileptogenic focus (EF) e perilesion area (PL), and control hippocampus from autopsy (n=5) were processed for glial protein (GFAP), activated microglia (IB4) immunohistochemistry, and metalloprotease activity (MMP-2, -9). Perilesional area showed GFAP positive cells with morphology of activate astrocyte and reactive gliosis nearby the lesion. In the lesion foci, astrocytes had altered cytoarchitecture with disorganized stroma suggestive of necrosis, and numerous mononuclear cells with few projections and morphological characteristics of activate microglia. Analysis of MMP-9 and MMP-2 in the sera before and after hippocampectomy confirmed the inflammatory pattern of TLE-HS, with high MMP-9 activity; high MMP-9/TIMP-1 and urokinase uPAR plasma levels before lobectomy but low after surgery. Maintenance of MMP-2 activity indicates persistent tissue remodeling in both groups. The present work shows that patients with chronic and medically intractable TLE-HS that undergone amigdalo-hippocampectomy for removal of epileptogenic lesion had a clinical enduring benefit of lack seizure recurrence for up to a year, and consistent reduction of proteases (MMP-9 and uPAR) activation that participate as important inflammatory epileptogenic inducers.

  3. A rapid and direct method for the determination of active site accessibility in proteins based on ESI-MS and active site titrations.

    PubMed

    O'Farrell, Norah; Kreiner, Michaela; Moore, Barry D; Parker, Marie-Claire

    2006-11-01

    We have developed an electrospray ionisation mass spectrometry (ESI-MS) technique that can be applied to rapidly determine the number of intact active sites in proteins. The methodology relies on inhibiting the protein with an active-site irreversible inhibitor and then using ESI-MS to determine the extent of inhibition. We have applied this methodology to a test system: a serine protease, subtilisin Carlsberg, and monitored the extent of inhibition by phenylmethylsulfonyl fluoride (PMSF), an irreversible serine hydrolase inhibitor as a function of the changes in immobilisation and hydration conditions. Two types of enzyme preparation were investigated, lyophilised enzymes and protein-coated microcrystals (PCMC).

  4. Nandrolone decanoate and resistance exercise training favor the occurrence of lesions and activate the inflammatory response in the ventral prostate.

    PubMed

    Gomes, F C; Chuffa, L G A; Scarano, W R; Pinheiro, P F F; Fávaro, W J; Domeniconi, R F

    2016-05-01

    Age is a key factor in the development of prostatic lesions. An increase in reactive oxygen species levels occurs during aging. Furthermore, the indiscriminate use of anabolic androgenic steroids and physical exercise alter the availability of hormones and may promote the appearance of lesions. This study examined whether the use of nandrolone decanoate (ND), associated or not with resistance exercise training, affects the pathways related to the inflammatory response in the ventral prostate of adult and aged rats. Sprague-Dawley rats were distributed into eight experimental groups: sedentary with ND, sedentary without ND, exercise with ND, and exercise without ND. The animals performed resistance exercise training and received ND two times/week (5 mg/kg, i.m.) for 8 weeks. Adult rats were killed immediately following treatment completion, and aged rats remained untreated until reaching 300 days of age. The adult animals that received ND and performed resistance exercise training showed a higher occurrence of lesions with TLR4 activation. Marked IL-6 expression occurred in the group that performed resistance exercise training. The group exposed to ND showed overexpression of TLR2, TLR4, NOX1, Nrf2, TNF-α, and P38MAPK. The animals that received ND and performed training showed increase levels of NFκB, IRF3, IL-6, TNF-α, and NOX1. TLR2 and TLR4 showed no upregulation in the aged animals. The groups exercise + ND showed lesions in the adult stage and after aging, followed by molecular alterations. We concluded that nandrolone decanoate and resistance exercise training can promote the onset of prostatic tumors in the adult stage, and during aging, activating pathways involved in the inflammatory response. PMID:27011054

  5. Detection by UPLC/ESI-TOF-MS of alkaloids in three Lycopodiaceae species from French Polynesia and their anticholinesterase activity.

    PubMed

    Ho, Raimana; Marsousi, Niloufar; Eugster, Philippe; Bianchini, Jean-Pierre; Raharivelomanana, Phila

    2009-10-01

    Three Lycopodiaceae species from French Polynesia, Lycopodium venustulum C. Gaudichaud, Lycopodiella cernua (C. Linnaeus) R. E. Pichi Sermolli and Lycopodium henryanum E. D. Brown were investigated for their alkaloidal composition by UHPLC/ESI-TOF-MS. Ten alkaloids were identified, with lycopodine and lycodoline being the main constituents in the three species. The acetylcholinesterase-inhibitory activities of the three species are probably due to the occurrence of huperzine A, huperzine B, huperzine E, huperzinine and lycopodine. PMID:19911569

  6. Pyrylium Salts as Reactive Matrices for MALDI-MS Imaging of Biologically Active Primary Amines

    NASA Astrophysics Data System (ADS)

    Shariatgorji, Mohammadreza; Nilsson, Anna; Källback, Patrik; Karlsson, Oskar; Zhang, Xiaoqun; Svenningsson, Per; Andren, Per E.

    2015-06-01

    Many neuroactive substances, including endogenous biomolecules, environmental compounds, and pharmaceuticals possess primary amine functional groups. Among these are catecholamine neurotransmitters (e.g., dopamine), many substituted phenethylamines (e.g., amphetamine), as well as amino acids and neuropeptides. In most cases, mass spectrometric (ESI and MALDI) analyses of trace amounts of such compounds are challenging because of their poor ionization properties. We present a method for chemical derivatization of primary amines by reaction with pyrylium salts that facilitates their detection by MALDI-MS and enables the imaging of primary amines in brain tissue sections. A screen of pyrylium salts revealed that the 2,4-diphenyl-pyranylium ion efficiently derivatizes primary amines and can be used as a reactive MALDI-MS matrix that induces both derivatization and desorption. MALDI-MS imaging with such matrix was used to map the localization of dopamine and amphetamine in brain tissue sections and to quantitatively map the distribution of the neurotoxin β- N-methylamino-L-alanine.

  7. Lesion-induced and activity-dependent structural plasticity of Purkinje cell dendritic spines in cerebellar vermis and hemisphere.

    PubMed

    Gelfo, Francesca; Florenzano, Fulvio; Foti, Francesca; Burello, Lorena; Petrosini, Laura; De Bartolo, Paola

    2016-09-01

    Neuroplasticity allows the brain to encode experience and learn behaviors, and also to re-acquire lost functions after damage. The cerebellum is a suitable structure to address this topic because of its strong involvement in learning processes and compensation of lesion-induced deficits. This study was aimed to characterize the effects of a hemicerebellectomy (HCb) combined or not with the exposition to environmental enrichment (EE) on dendritic spine density and size in Purkinje cell proximal and distal compartments of cerebellar vermian and hemispherical regions. Male Wistar rats were housed in enriched or standard environments from the 21st post-natal day (pnd) onwards. At the 75th pnd, rats were submitted to HCb or sham lesion. Neurological symptoms and spatial performance in the Morris water maze were evaluated. At the end of testing, morphological analyses assessed dendritic spine density, area, length, and head diameter on vermian and hemispherical Purkinje cells. All hemicerebellectomized (HCbed) rats showed motor compensation, but standard-reared HCbed animals exhibited cognitive impairment that was almost completely compensated in enriched HCbed rats. The standard-reared HCbed rats showed decreased density with augmented size of Purkinje cell spines in the vermis, and augmented both density and size in the hemisphere. Enriched HCbed rats almost completely maintained the spine density and size induced by EE. Both lesion-induced and activity-dependent cerebellar plastic changes may be interpreted as "beneficial" brain reactions, aimed to support behavioral performance rescuing. PMID:26420278

  8. Antioxidant and genoprotective activity of selected cucurbitaceae seed extracts and LC-ESIMS/MS identification of phenolic components.

    PubMed

    Yasir, Muhammad; Sultana, Bushra; Nigam, Poonam Singh; Owusu-Apenten, Richard

    2016-05-15

    Cucurbitaceae are one of most widely used plant species for human food but lesser known members have not been examined for bioactive components. The purpose of this study was to evaluate the antioxidant and genoprotective activities from three cucurbitaceae seeds extracts and to identify phenolic components by LC-ESIMS/MS analysis. From the results, the yield of seeds extract was 20-41% (w/w) and samples had 16-40% total phenols as gallic acid equivalents (GAE). Compared with methanol solvent, using acidified methanol led to increased extraction yield by 1.4 to 10-fold, higher phenolic content (149.5 ± 1.2 to 396.4 ± 1.9 mg GAE/g), higher DPPH radical quenching and enhanced genoprotective activity using the pBR322 plasmid assay. LC-ESI-MS/MS analysis led to identification of 14-17 components, based on authentic standards and comparison with literature reports, as mainly phenolic acids and esters, flavonol glycosides. This may be the first mass spectrometric profiling of polyphenol components from cucurbitaceae seeds.

  9. Antioxidant and genoprotective activity of selected cucurbitaceae seed extracts and LC-ESIMS/MS identification of phenolic components.

    PubMed

    Yasir, Muhammad; Sultana, Bushra; Nigam, Poonam Singh; Owusu-Apenten, Richard

    2016-05-15

    Cucurbitaceae are one of most widely used plant species for human food but lesser known members have not been examined for bioactive components. The purpose of this study was to evaluate the antioxidant and genoprotective activities from three cucurbitaceae seeds extracts and to identify phenolic components by LC-ESIMS/MS analysis. From the results, the yield of seeds extract was 20-41% (w/w) and samples had 16-40% total phenols as gallic acid equivalents (GAE). Compared with methanol solvent, using acidified methanol led to increased extraction yield by 1.4 to 10-fold, higher phenolic content (149.5 ± 1.2 to 396.4 ± 1.9 mg GAE/g), higher DPPH radical quenching and enhanced genoprotective activity using the pBR322 plasmid assay. LC-ESI-MS/MS analysis led to identification of 14-17 components, based on authentic standards and comparison with literature reports, as mainly phenolic acids and esters, flavonol glycosides. This may be the first mass spectrometric profiling of polyphenol components from cucurbitaceae seeds. PMID:26775976

  10. Whole-cell MALDI-TOF MS: a new tool to assess the multifaceted activation of macrophages.

    PubMed

    Ouedraogo, Richard; Daumas, Aurélie; Ghigo, Eric; Capo, Christian; Mege, Jean-Louis; Textoris, Julien

    2012-10-22

    Whole-cell MALDI-TOF MS is routinely used to identify bacterial species in clinical samples. This technique has also proven to allow identification of intact mammalian cells, including macrophages. Here, we wondered whether this approach enabled the assessment human macrophages plasticity. The whole-cell MALDI-TOF spectra of macrophages stimulated with IFN-γ and IL-4, two inducers of M1 and M2 macrophage polarisation, consisted of peaks ranging from 2 to 12 kDa. The spectra of unstimulated and stimulated macrophages were clearly different. The fingerprints induced by the M1 agonists, IFN-γ, TNF, LPS and LPS+IFN-γ, and the M2 agonists, IL-4, TGF-β1 and IL-10, were specific and readily identifiable. Thus, whole-cell MALDI-TOF MS was able to characterise M1 and M2 macrophage subtypes. In addition, the fingerprints induced by extracellular (group B Streptococcus, Staphylococcus aureus) or intracellular (BCG, Orientia tsutsugamushi, Coxiella burnetii) bacteria were bacterium-specific. The whole-cell MALDI-TOF MS fingerprints therefore revealed the multifaceted activation of human macrophages. This approach opened a new avenue of studies to assess the immune response in the clinical setting, by monitoring the various activation patterns of immune cells in pathological conditions.

  11. Moderate Physical Activity Mediates the Association between White Matter Lesion Volume and Memory Recall in Breast Cancer Survivors

    PubMed Central

    Cooke, Gillian E.; Wetter, Nathan C.; Banducci, Sarah E.; Mackenzie, Michael J.; Zuniga, Krystle E.; Awick, Elizabeth A.; Roberts, Sarah A.; Sutton, Brad P.; McAuley, Edward; Kramer, Arthur F.

    2016-01-01

    Increased survival rates among breast cancer patients have drawn significant attention to consequences of both the presence of cancer, and the subsequent treatment-related impact on the brain. The incidence of breast cancer and the effects of treatment often result in alterations in the microstructure of white matter and impaired cognitive functioning. However, physical activity is proving to be a successful modifiable lifestyle factor in many studies that could prove beneficial to breast cancer survivors. This study investigates the link between white matter lesion volume, moderate physical activity, and cognition in breast cancer survivors following treatment compared to non-cancer age-matched controls. Results revealed that brain structure significantly predicted cognitive function via mediation of physical activity in breast cancer survivors. Overall, the study provided preliminary evidence suggesting moderate physical activity may help reduce the treatment related risks associated with breast cancer, including changes to WM integrity and cognitive impairment. PMID:26915025

  12. The development of an MRI lesion quantifying system for multiple sclerosis patients undergoing treatment

    NASA Astrophysics Data System (ADS)

    Moin, Paymann; Ma, Kevin; Amezcua, Lilyana; Gertych, Arkadiusz; Liu, Brent

    2009-02-01

    Multiple sclerosis (MS) is a demyelinating disease of the central nervous system that affects approximately 2.5 million people worldwide. Magnetic resonance imaging (MRI) is an established tool for the assessment of disease activity, progression and response to treatment. The progression of the disease is variable and requires routine follow-up imaging studies. Currently, MRI quantification of multiple sclerosis requires a manual approach to lesion measurement and yields an estimate of lesion volume and interval change. In the setting of several prior studies and a long treatment history, trends related to treatment change quickly become difficult to extrapolate. Our efforts seek to develop an imaging informatics based MS lesion computer aided detection (CAD) package to quantify and track MS lesions including lesion load, volume, and location. Together, with select clinical parameters, this data will be incorporated into an MS specific e- Folder to provide decision support to evaluate and assess treatment options for MS in a manner tailored specifically to an individual based on trends in MS presentation and progression.

  13. Varietal classification and antioxidant activity prediction of Osmanthus fragrans Lour. flowers using UPLC-PDA/QTOF-MS and multivariable analysis.

    PubMed

    Zhou, Fei; Peng, Jiyu; Zhao, Yajing; Huang, Weisu; Jiang, Yirong; Li, Maiquan; Wu, Xiaodan; Lu, Baiyi

    2017-02-15

    This study was aimed to classify the varieties and predict the antioxidant activity of Osmanthus fragrans flowers by UPLC-PDA/QTOF-MS and multivariable analysis. The PLS-DA model successfully classified the four varieties based on both the 21 identified compounds and the effective compounds. For the antioxidant activity prediction, PLS performed well to predict the antioxidant activity of O. fragrans flowers. Furthermore, acteoside, suspensaside A, ligustroside, forsythoside A, phillygenin and caffeic acid were selected as effective compounds by UVE-SPA for prediction. On the basis of effective compounds, PLS, MLR and PCR were applied to establish the calibration models. The UVE-SPA-MLR model was the optimal method to predict the antioxidant activity values with Rp of 0.9200, 0.9010 and 0.8905 for DPPH, ABTS and FRAP assays, respectively. The results revealed that the UPLC-PDA/QTOF-MS combined with chemometrics could be a new method to classify the varieties and predict the antioxidant activity of O. fragrans flowers. PMID:27664663

  14. Event-related oscillations (ERO) during an active discrimination task: Effects of lesions of the nucleus basalis magnocellularis.

    PubMed

    Sanchez-Alavez, Manuel; Ehlers, Cindy L

    2016-05-01

    The cholinergic system in the brain is involved in attentional processes that are engaged for the identification and selection of relevant information in the environment and the formation of new stimulus associations. In the present study we determined the effects of cholinergic lesions of nucleus basalis magnocellularis (NBM) on amplitude and phase characteristics of event related oscillations (EROs) generated in an auditory active discrimination task in rats. Rats were trained to press a lever to begin a series of 1kHz tones and to release the lever upon hearing a 2kHz tone. A time-frequency based representation was used to determine ERO energy and phase synchronization (phase lock index, PLI) across trials, recorded within frontal cortical structures. Lesions in NBM produced by an infusion of a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) resulted in (1) a reduction of the number of correct behavioral responses in the active discrimination task, (2) an increase in ERO energy in the delta frequency bands, (3) an increase in theta, alpha and beta ERO energy in the N1, P3a and P3b regions of interest (ROI), and (4) an increase in PLI in the theta frequency band in the N1 ROIs. These studies suggest that the NBM cholinergic system is involved in maintaining the synchronization/phase resetting of oscillations in different frequencies in response to the presentation of the target stimuli in an active discrimination task. PMID:25660307

  15. High-Throughput LC-MS/MS Proteomic Analysis of a Mouse Model of Mesiotemporal Lobe Epilepsy Predicts Microglial Activation Underlying Disease Development.

    PubMed

    Bitsika, Vasiliki; Duveau, Venceslas; Simon-Areces, Julia; Mullen, William; Roucard, Corinne; Makridakis, Manousos; Mermelekas, George; Savvopoulos, Pantelis; Depaulis, Antoine; Vlahou, Antonia

    2016-05-01

    Uncovering the molecular mechanisms of mesiotemporal lobe epilepsy (MTLE) is critical to identify therapeutic targets. In this study, we performed global protein expression analysis of a kainic acid (KA) MTLE mouse model at various time-points (1, 3, and 30 days post-KA injection -dpi), representing specific stages of the syndrome. High-resolution liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), in combination with label-free protein quantification using three processing approaches for quantification, was applied. Following comparison of KA versus NaCl-injected mice, 22, 53, and 175 proteins were differentially (statistically significant) expressed at 1, 3 and 30dpi, respectively, according to all three quantification approaches. Selected findings were confirmed by multiple reaction monitoring LC-MS/MS. As a positive control, the astrocyte marker GFAP was found to be upregulated (3dpi: 1.9 fold; 30dpi: 12.5 fold), also verified by IHC. The results collectively suggest that impairment in synaptic transmission occurs even right after initial status epilepticus (1dpi), with neurodegeneration becoming more extensive during epileptogenesis (3dpi) and sustained at the chronic phase (30dpi), where also extensive glial- and astrocyte-mediated inflammation is evident. This molecular profile is in line with observed phenotypic changes in human MTLE, providing the basis for future studies on new molecular targets for the disease. PMID:27057777

  16. HPLC and HPLC/MS/MS Studies on Stress, Accelerated and Intermediate Degradation Tests of Antivirally Active Tricyclic Analog of Acyclovir.

    PubMed

    Lesniewska, Monika A; Dereziński, Paweł; Klupczyńska, Agnieszka; Kokot, Zenon J; Ostrowski, Tomasz; Zeidler, Joanna; Muszalska, Izabela

    2015-01-01

    The degradation behavior of a tricyclic analog of acyclovir [6-(4-MeOPh)-TACV] was determined in accordance with International Conference on Harmonization guidelines for good clinical practice under different stress conditions (neutral hydrolysis, strong acid/base degradation, oxidative decomposition, photodegradation, and thermal degradation). Accelerated [40±2°C/75%±5% relative humidity (RH)] and intermediate (30±2°C/65%±5% RH) stability tests were also performed. For observation of the degradation of the tested compound the RP-HPLC was used, whereas for the analysis of its degradation products HPLC/MS/MS was used. Degradation of the tested substance allowed its classification as unstable in neutral environment, acidic/alkaline medium, and in the presence of oxidizing agent. The tested compound was also light sensitive and was classified as photolabile both in solution and in the solid phase. However, the observed photodegradation in the solid phase was at a much lower level than in the case of photodegradation in solution. The study showed that both air temperature and RH had no significant effect on the stability of the tested substance during storage for 1 month at 100°C (dry heat) as well as during accelerated and intermediate tests. Based on the HPLC/MS/MS analysis, it can be concluded that acyclovir was formed as a degradation product of 6-(4-MeOPh)-TACV.

  17. APNTP Inactivation of MS2 Bacteriophage: Effect of operating parameters on virucidal activity

    NASA Astrophysics Data System (ADS)

    Alshraiedeh, Nid'a.; Alkawareek, Mahmoud; Gorman, Sean; Graham, William; Gilmore, Brendan

    2013-09-01

    Atmospheric pressure non-thermal plasmas (APNTP) provide a promising alternative method for surface decontamination. Norovirus is globally the most common etiological agent of acute non-bacterial gastroenteritis outbreaks. APNTP have proven to be effective in inactivation of MS2 bacteriophages, widely employed as surrogate for human norovirus. Here we explore the optimization of a helium-based kHz APNTP by varying the oxygen concentration (from 0 to 0.75%) in the feed gas and the operating frequency (from 10 to 40 kHz). It has been established that both these changes increase the reactive oxide concentration in the plume and we see a correlation between both increasing oxygen concentration and operating frequency and reduction in survival density of treated bacteriophages. For example increasing the O2 concentration from 0 to 0.5 to 0.75% increased the log reduction from 4.98 to 5.93 to 7.06, respectively. These results will be discussed in the context of recent studies where singlet delta oxygen was shown to cause MS2 phage inactivation., Q T Algwari, PhD Thesis QUB (2011).

  18. Oxidized guanine lesions and hOgg1 activity in lung cancer.

    PubMed

    Mambo, Elizabeth; Chatterjee, Aditi; de Souza-Pinto, Nadja C; Mayard, Sabine; Hogue, Barbara A; Hoque, Mohammad O; Dizdaroglu, Miral; Bohr, Vilhelm A; Sidransky, David

    2005-06-30

    In humans, the oxidatively induced DNA lesion 8-hydroxyguanine (8-oxoG) is removed from DNA by hOgg1, a DNA glycosylase/AP lyase that specifically incises 8-oxoG opposite cytosine. We analysed the expression of hOGG1 mRNA in 18 lung cancer and three normal cell lines. Although hOGG1 was overexpressed in most cell lines, 2/18 (11.1%) showed a lower hOGG1 mRNA and protein expression (approximately 80% decrease) relative to normal cell lines. Liquid chromatography/mass spectrometry analysis showed increased levels of 8-oxoG in the two cell lines with the lowest hOGG1 mRNA expression. We examined the ability of nuclear and mitochondrial extracts to incise 8-oxoG lesion in cell lines H1650 and H226 expressing lower hOGG1 mRNA and H1915 and H1975 with higher than normal hOGG1 mRNA expression. Both nuclear and mitochondrial extracts from H1915 and H1975 cells were proficient in 8-oxoG removal. However, both cell lines with the lowest hOGG1 mRNA expression exhibited a severe reduction in 8-oxoG incision in both nuclear and mitochondrial extracts. Under-expression of hOGG1 mRNA and hOgg1 protein was associated with a decrease in mitochondrial DNA repair in response to oxidative damaging agents. These results provide evidence for defective incision of 8-oxoG in both nuclear and mitochondria of H1650 and H226 lung cancer cell lines. These results may implicate 8-oxoG repair defects in certain lung cancers.

  19. Relationship between methanesulfonate (MS-) in atmospheric particulate and remotely sensed phytoplankton activity in oligo-mesotrophic central Mediterranean Sea

    NASA Astrophysics Data System (ADS)

    Becagli, S.; Lazzara, L.; Fani, F.; Marchese, C.; Traversi, R.; Severi, M.; di Sarra, A.; Sferlazzo, D.; Piacentino, S.; Bommarito, C.; Dayan, U.; Udisti, R.

    2013-11-01

    The coupling between oceanic and atmospheric sulfur cycles is fundamental for the understanding of the role of sulfate particles as potential climate regulators. We discuss existing relationships among methanesulfonate (MS- - one of the end products of oxidation of biogenic dimethylsulfide - DMS) in the atmospheric particulate, phytoplankton biomass, and remotely-sensed activity in the central Mediterranean. The MS- concentration in the aerosol particles is based on PM10 sampling (from 2005 to 2008) of atmospheric aerosols at the island of Lampedusa (35.5°N, 12.6°E) in the central Mediterranean Sea. The marine primary production in the sea sector surrounding the sampling site is obtained by using Ocean Color remote sensed data (SeaWiFS, MODIS-Aqua). In particular, primary production is calculated using a bio-optical model of sea reflectance and a Wavelength-Depth-Resolved Model (WDRM), fed by elaborated satellite data (chlorophyll concentration in the euphotic layer - Chl, sea surface temperature) and daily solar surface irradiance measurements. The multi-year evolution of MS- atmospheric concentration shows a well-defined seasonal cycle with a summer maximum, corresponding to the annual peak of solar radiation and a minimum of phytoplankton biomass (expressed as Chl). Statistically significant linear relationships between monthly means of atmospheric MS- and both the phytoplankton productivity index PB (r2 = 0.84, p < 0.001) and the solar radiation dose (SRD; r2 = 0.87, p < 0.001) in the upper mixed layer of the sea around Lampedusa are found. These correlations are mainly driven by the common seasonal pattern and suggest that DMS production in the marine surface layer is mainly related to the phytoplankton physiology. High values of PB are also the expression of stressed cells. The main stress factors in Mediterranean Sea during summer are high irradiance and shallow depth of the upper mixed layer, which lead to enhanced DMS emissions and higher MS- amounts in

  20. Alkaloid metabolite profiles by GC/MS and acetylcholinesterase inhibitory activities with binding-mode predictions of five Amaryllidaceae plants.

    PubMed

    Cortes, Natalie; Alvarez, Rafael; Osorio, Edison H; Alzate, Fernando; Berkov, Strahil; Osorio, Edison

    2015-01-01

    Acetylcholinesterase (AChE) enzymatic inhibition is an important target for the management of Alzheimer disease (AD) and AChE inhibitors are the mainstay drugs for its treatment. In order to discover new sources of potent AChE inhibitors, a combined strategy is presented based on AChE-inhibitory activity and chemical profiles by GC/MS, together with in silico studies. The combined strategy was applied on alkaloid extracts of five Amaryllidaceae species that grow in Colombia. Fifty-seven alkaloids were detected using GC/MS, and 21 of them were identified by comparing their mass-spectral fragmentation patterns with standard reference spectra in commercial and private library databases. The alkaloid extracts of Zephyranthes carinata exhibited a high level of inhibitory activity (IC50 = 5.97 ± 0.24 μg/mL). Molecular modeling, which was performed using the structures of some of the alkaloids present in this extract and the three-dimensional crystal structures of AChE derived from Torpedo californica, disclosed their binding configuration in the active site of this AChE. The results suggested that the alkaloids 3-epimacronine and lycoramine might be of interest for AChE inhibition. Although the galanthamine group is known for its potential utility in treating AD, the tazettine-type alkaloids should be evaluated to find more selective compounds of potential benefit for AD. PMID:25305596

  1. Generation, characterization and in vivo biological activity of two distinct monoclonal anti-PEG IgMs

    SciTech Connect

    Hashimoto, Yosuke; Shimizu, Taro; Mima, Yu; Abu Lila, Amr S.; Ishida, Tatsuhiro; Kiwada, Hiroshi

    2014-05-15

    PEGylation, the attachment of polyethylene glycol (PEG) to nanocarriers and proteins, is a widely accepted approach to improving the in vivo efficacy of the non-PEGylated products. However, both PEGylated liposomes and PEGylated proteins reportedly trigger the production of specific antibodies, mainly IgM, against the PEG moiety, which possibly leads to a reduction in safety and therapeutic efficacy of the PEGylated products. In the present study, two monoclonal anti-PEG IgMs — HIK-M09 via immunization with an intravenous injection of PEGylated liposomes (SLs) and HIK-M11 via immunization with a subcutaneous administration of PEGylated ovalbumin (PEG-OVA) were successfully generated. The generated IgMs showed efficient reactivity to mPEG{sub 2000} conjugated to 1,2-distearoyl-sn-glycero-3-phospho-ethanolamine (DSPE), PEGylated liposome (SL) and PEG-OVA. It appears that HIK-M09 recognizes ethoxy (OCH{sub 2}CH{sub 2}) repeat units along with a terminal motif of PEG, while HIK-M11 recognizes only ethoxy repeat units of PEG. Such unique properties allow HIK-M09 to bind with dense PEG. In addition, their impact on the in vivo clearance of the PEGylated products was investigated. It was found that the generated ant-PEG IgMs induced a clearance of SL as they were intravenously administered with SL. Interestingly, the HIK-M11, generated by PEG-OVA, induced the clearance of both SL and PEG-OVA, while the HIK-M09, generated by SL, induced the clearance of SL only. We here revealed that the presence of serum anti-PEG IgM and the subsequent binding of anti-PEG IgM to the PEGylated products are not necessarily related to the enhanced clearance of the products. It appears that subsequent complement activation following anti-PEG IgM binding is the most important step in dictating the in vivo fate of PEGylated products. This study may have implications for the design, development and clinical application of PEGylated products and therapeutics. - Highlights: • Two monoclonal

  2. Objectively measured physical activity, brain atrophy, and white matter lesions in older adults with mild cognitive impairment.

    PubMed

    Doi, Takehiko; Makizako, Hyuma; Shimada, Hiroyuki; Tsutsumimoto, Kota; Hotta, Ryo; Nakakubo, Sho; Park, Hyuntae; Suzuki, Takao

    2015-02-01

    Physical activity may help to prevent or delay brain atrophy. Numerous studies have shown associations between physical activity and age-related changes in the brain. However, most of these studies involved self-reported physical activity, not objectively measured physical activity. Therefore, the aim of this study was to examine the association between objectively measured physical activity, as determined using accelerometers, and brain magnetic resonance imaging (MRI) measures in older adults with mild cognitive impairment (MCI). We analyzed 323 older subjects with MCI (mean age 71.4 years) who were recruited from the participants of the Obu Study of Health Promotion for the Elderly. We recorded demographic data and measured physical activity using a tri-axial accelerometer. Physical activity was classified as light-intensity physical activity (LPA) or moderate-to-vigorous physical activity (MVPA). Brain atrophy and the severity of white matter lesions (WML) were determined by MRI. Low levels of LPA and MVPA were associated with severe WML. Subjects with severe WML were older, had lower mobility, and had greater brain atrophy than subjects with mild WML (all P<0.05). Multivariate analysis revealed that more MVPA was associated with less brain atrophy, even after adjustment for WML (β=-0.126, P=0.015), but LPA was not (β=-0.102, P=0.136). Our study revealed that objectively measured physical activity, especially MVPA, was associated with brain atrophy in MCI subjects, even after adjusting for WML. These findings support the hypothesis that physical activity plays a crucial role in maintaining brain health.

  3. Dietary n-3 polyunsaturated fatty acids prevent the development of atherosclerotic lesions in mice. Modulation of macrophage secretory activities.

    PubMed

    Renier, G; Skamene, E; DeSanctis, J; Radzioch, D

    1993-10-01

    We examined the effects of dietary n-3 polyunsaturated and saturated fatty acids on the development of the atherogenic process in mice and on the macrophage ability to secrete several effector molecules that may be involved in the atherogenic process. The secretion of inflammatory proteins such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) and the production of lipoprotein lipase (LPL), nitrogen oxide (NO2), and prostaglandin E2 (PGE2) were evaluated in peritoneal macrophages isolated from atherosclerosis-susceptible C57BL/6J mice. The mice were assigned at random to three experimental groups: the first group was fed a semi-defined control diet (control diet); the second group was maintained on the control diet supplemented with 10% menhaden oil (menhaden diet); and the third group received the control diet supplemented with 10% palm oil plus 2% cholesterol (saturated fat diet). Macrophages derived from mice fed the menhaden diet showed a suppression of their basal TNF-alpha mRNA expression and production. They also presented a dramatically decreased ability to express TNF-alpha and IL-1 beta mRNAs in response to exposure to lipopolysaccharide (LPS) compared with the macrophages from the control group. LPL mRNA and protein expression were downregulated after 6 and 15 weeks of menhaden-diet feeding. Significantly higher NO2 production in response to interferon gamma was found, both after 6 and 15 weeks of diet feeding, in the menhaden group compared with the control group. In addition, prostaglandin production and macrophage tumoricidal activity in response to LPS were decreased in this group compared with the control group. Macrophages derived from the saturated fat group did not show any significant alterations in TNF-alpha, LPL, NO2, or PGE2 secretion compared with controls. Interestingly, we observed a progressive increase of the LPS-induced IL-1 beta gene expression and secretion among macrophages harvested from mice receiving

  4. Anti-malarial activity and HS-SPME-GC-MS chemical profiling of Plinia cerrocampanensis leaf essential oil

    PubMed Central

    2014-01-01

    Background Plinia cerrocampanensis is an endemic plant of Panama. The leaf essential oil of this plant has shown antibacterial activity. However, anti-malarial activity and chemical profiling by HS-SPME-GC-MS of this essential oil have not been reported before. Methods Anti-malarial activity of the essential oil (EO) was evaluated in vitro against chloroquine-sensitive HB3 and chloroquine-resistant W2 strains of Plasmodium falciparum. Synergistic effect of chloroquine and the EO on parasite growth was evaluated by calculating the combination index. A methodology involving headspace solid phase microextraction and gas chromatography-mass spectrometry (HS-SPME-GC-MS) was developed to investigate the composition of Plinia cerrocampanensis EO. Results Plinia cerrocampanensis EO showed a high anti-malarial activity and a synergistic interaction with chloroquine. The Plinia cerrocampanensis EO inhibited P. falciparum growth in vitro at an IC50 of 7.3 μg/mL. Chloroquine together with the EO decreased the IC50 of chloroquine from 0.1 μg/mL to 0.05 μg/mL, and of the EO from 7.3 μg/mL to 1.1 μg/mL. The measured combination index was 0.58, which clearly indicates that the EO acts synergistically with chloroquine. Since the EO maintained its inhibitory activity on the chloroquine-sensitive strain of the parasite, it could be acting by a different mechanism of action than chloroquine. The best HS-SPME-GC-MS analytical conditions were obtained when the temperature of extraction was 49°C, incubation time 14 min, and the time of extraction 10 min. This method allowed for the identification of 53 volatile constituents in the EO, including new compounds not reported earlier. Conclusions The anti-malarial activity exhibited by the Plinia cerrocampanensis EO may lend support for its possible use as an alternative for anti-malarial therapy. PMID:24410874

  5. Subependymal giant cell astrocytoma: a lesion with activated mTOR pathway and constant expression of glutamine synthetase.

    PubMed

    Buccoliero, Anna Maria; Caporalini, Chiara; Giordano, Flavio; Mussa, Federico; Scagnet, Mirko; Moscardi, Selene; Baroni, Gianna; Genitori, Lorenzo; Taddei, Gian Luigi

    2016-01-01

    Subependymal giant-cell astrocytoma (SEGA) is a rare tumor associated with tuberous sclerosis complex (TSC). TSC mainly involves the central nervous system (CNS) where SEGA, subependymal nodules, and cortical tubers may be present. First studies suggested the astrocytic nature of SEGA while successive studies demonstrated the mixed glio-neuronal nature. There are similarities between TSC-associated CNS lesions and type IIb focal cortical dysplasia (FCD). In all these pathologies, mammalian target of rapamycin (mTOR) pathway activation has been demonstrated. Recent data evidenced that balloon cells in FCD IIb express glutamine synthetase (GS). GS is involved in the clearance of glutamate. Cells expressing GS might exert an antiepileptic role. We evaluated by immunohistochemistry the glial fibrillary acidic protein (GFAP), neurofilaments (NF), and GS expression and the mTOR status (mTOR and phosphorylated ribosomal protein S6) in 16 SEGAs and 2 cortical tubers. Our purpose was to emphasize the mixed nature of SEGA and to further investigate the similarities between TSC-related CNS lesions (in particular SEGA) and FCD IIb. We confirm the glio-neuronal nature and the common activation of the mTOR pathway in SEGAs. In addition, we report for the first time that these tumors, analogously to FCD IIb, commonly express GS. Notably, the expression of mTOR, phosphorylated ribosomal protein S6, and GS was restricted to gemistocytic-like GFAP-negative cells. GS expression and mTOR pathway activation were also documented in cortical tubers. Further studies are necessary to understand the significance of GS expression in SEGAs as well as in cortical tubers. PMID:27390104

  6. Subependymal giant cell astrocytoma: a lesion with activated mTOR pathway and constant expression of glutamine synthetase.

    PubMed

    Buccoliero, Anna Maria; Caporalini, Chiara; Giordano, Flavio; Mussa, Federico; Scagnet, Mirko; Moscardi, Selene; Baroni, Gianna; Genitori, Lorenzo; Taddei, Gian Luigi

    2016-01-01

    Subependymal giant-cell astrocytoma (SEGA) is a rare tumor associated with tuberous sclerosis complex (TSC). TSC mainly involves the central nervous system (CNS) where SEGA, subependymal nodules, and cortical tubers may be present. First studies suggested the astrocytic nature of SEGA while successive studies demonstrated the mixed glio-neuronal nature. There are similarities between TSC-associated CNS lesions and type IIb focal cortical dysplasia (FCD). In all these pathologies, mammalian target of rapamycin (mTOR) pathway activation has been demonstrated. Recent data evidenced that balloon cells in FCD IIb express glutamine synthetase (GS). GS is involved in the clearance of glutamate. Cells expressing GS might exert an antiepileptic role. We evaluated by immunohistochemistry the glial fibrillary acidic protein (GFAP), neurofilaments (NF), and GS expression and the mTOR status (mTOR and phosphorylated ribosomal protein S6) in 16 SEGAs and 2 cortical tubers. Our purpose was to emphasize the mixed nature of SEGA and to further investigate the similarities between TSC-related CNS lesions (in particular SEGA) and FCD IIb. We confirm the glio-neuronal nature and the common activation of the mTOR pathway in SEGAs. In addition, we report for the first time that these tumors, analogously to FCD IIb, commonly express GS. Notably, the expression of mTOR, phosphorylated ribosomal protein S6, and GS was restricted to gemistocytic-like GFAP-negative cells. GS expression and mTOR pathway activation were also documented in cortical tubers. Further studies are necessary to understand the significance of GS expression in SEGAs as well as in cortical tubers.

  7. Characterization of estrogen and androgen activity of food contact materials by different in vitro bioassays (YES, YAS, ERα and AR CALUX) and chromatographic analysis (GC-MS, HPLC-MS).

    PubMed

    Mertl, Johannes; Kirchnawy, Christian; Osorio, Veronica; Grininger, Angelika; Richter, Alexander; Bergmair, Johannes; Pyerin, Michael; Washüttl, Michael; Tacker, Manfred

    2014-01-01

    Endocrine active substances (EAS) show structural similarities to natural hormones and are suspected to affect the human endocrine system by inducing hormone dependent effects. Recent studies with in vitro tests suggest that EAS can leach from packaging into food and may therefore pose a risk to human health. Sample migrates from food contact materials were tested for estrogen and androgen agonists and antagonists with different commonly used in vitro tests. Additionally, chemical trace analysis by GC-MS and HPLC-MS was used to identify potential hormone active substances in sample migrates. A GC-MS method to screen migrates for 29 known or potential endocrine active substances was established and validated. Samples were migrated according to EC 10/2011, concentrated by solid phase extraction and tested with estrogen and androgen responsive reporter gene assays based on yeast cells (YES and YAS) or human osteoblast cells (ERα and AR CALUX). A high level of agreement between the different bioassays could be observed by screening for estrogen agonists. Four out of 18 samples tested showed an estrogen activity in a similar range in both, YES and ERα CALUX. Two more samples tested positive in ERα CALUX due to the lower limits of detection in this assay. Androgen agonists could not be detected in any of the tested samples, neither with YAS nor with AR CALUX. When testing for antagonists, significant differences between yeast and human cell-based bioassays were noticed. Using YES and YAS many samples showed a strong antagonistic activity which was not observed using human cell-based CALUX assays. By GC-MS, some known or supposed EAS were identified in sample migrates that showed a biological activity in the in vitro tests. However, no firm conclusions about the sources of the observed hormone activity could be obtained from the chemical results.

  8. Characterization of Estrogen and Androgen Activity of Food Contact Materials by Different In Vitro Bioassays (YES, YAS, ERα and AR CALUX) and Chromatographic Analysis (GC-MS, HPLC-MS)

    PubMed Central

    Osorio, Veronica; Grininger, Angelika; Richter, Alexander; Bergmair, Johannes; Pyerin, Michael; Washüttl, Michael; Tacker, Manfred

    2014-01-01

    Endocrine active substances (EAS) show structural similarities to natural hormones and are suspected to affect the human endocrine system by inducing hormone dependent effects. Recent studies with in vitro tests suggest that EAS can leach from packaging into food and may therefore pose a risk to human health. Sample migrates from food contact materials were tested for estrogen and androgen agonists and antagonists with different commonly used in vitro tests. Additionally, chemical trace analysis by GC-MS and HPLC-MS was used to identify potential hormone active substances in sample migrates. A GC-MS method to screen migrates for 29 known or potential endocrine active substances was established and validated. Samples were migrated according to EC 10/2011, concentrated by solid phase extraction and tested with estrogen and androgen responsive reporter gene assays based on yeast cells (YES and YAS) or human osteoblast cells (ERα and AR CALUX). A high level of agreement between the different bioassays could be observed by screening for estrogen agonists. Four out of 18 samples tested showed an estrogen activity in a similar range in both, YES and ERα CALUX. Two more samples tested positive in ERα CALUX due to the lower limits of detection in this assay. Androgen agonists could not be detected in any of the tested samples, neither with YAS nor with AR CALUX. When testing for antagonists, significant differences between yeast and human cell-based bioassays were noticed. Using YES and YAS many samples showed a strong antagonistic activity which was not observed using human cell-based CALUX assays. By GC-MS, some known or supposed EAS were identified in sample migrates that showed a biological activity in the in vitro tests. However, no firm conclusions about the sources of the observed hormone activity could be obtained from the chemical results. PMID:25000404

  9. Dorsomedial hypothalamic lesions counteract decreases in locomotor activity in male Syrian hamsters transferred from long to short day lengths.

    PubMed

    Jarjisian, Stephan G; Butler, Matthew P; Paul, Matthew J; Place, Ned J; Prendergast, Brian J; Kriegsfeld, Lance J; Zucker, Irving

    2015-02-01

    The dorsomedial nucleus (DMN) of the hypothalamus has been implicated in seasonal control of reproduction. Syrian hamsters with DMN lesions, unlike control hamsters, do not undergo testicular regression after transfer from a long day length (14 h of light per day; LD) to a short day length (8 h of light per day; SD). SDs also markedly reduce hamster locomotor activity (LMA). To assess whether the DMN is a component of the neural circuitry that mediates seasonal variation in LMA, neurologically intact males (controls) and hamsters that had sustained lesions of the DMN (DMNx) were housed in an LD or SD photoperiod for 26 weeks. DMNx that prevented testicular regression counteracted decreases in LMA during 8 to10 weeks of SD treatment; steroid-independent effects of SDs did not override high levels of LMA in DMNx males. As in previous studies, testosterone (T) restoration increased LMA in LD but not SD castrated control males. In the present study, T also failed to increase LMA in SD-DMNx hamsters. The DMN is not necessary to maintain decreased responsiveness of locomotor activity systems to T in SDs, which presumably is mediated by other central nervous system androgen target tissues. Finally, DMNx did not interfere with the spontaneous increase in LMA exhibited by photorefractory hamsters after 26 weeks of SD treatment. We propose that DMN is an essential part of the substrate that mediates seasonal decreases in LMA as day length decreases but is not required to sustain decreased SD responsiveness to T or for development of refractoriness to SDs.

  10. Simultaneous determination of spironolactone and its active metabolite canrenone in human plasma by HPLC-APCI-MS.

    PubMed

    Dong, Haijuan; Xu, Fengguo; Zhang, Zunjian; Tian, Yuan; Chen, Yun

    2006-04-01

    A sensitive and specific liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry (LC-APCI-MS) method for the simultaneous determination of spironolactone and its active metabolite canrenone in human plasma has been developed and validated. After the addition of estazolam as the internal standard (IS), plasma samples were extracted with methylene chloride : ethyl acetate mixture (20 : 80, v/v) and separated by high-performance liquid chromatography (HPLC) on a reversed-phase C18 column with a mobile phase of methanol-water (57 : 43, v/v). Analytes were determined in a single quadrupole mass spectrometer using an atmospheric pressure chemical ionization (APCI) source. LC-APCI-MS was performed in the selected-ion monitoring (SIM) mode using target ions at m/z 341.25 for spironolactone and canrenone, m/z 295.05 for estazolam. The method was proved to be sensitive and specific by testing six different plasma batches. Calibration curves of spironolactone and canrenone were linear over the range 2-300 ng/ml. The within- and between-batch precisions (relative standard deviation (RSD)%) were lower than 10% and the accuracy ranged from 85 to 115%. The lower limit of quantification (LLOQ) was identifiable and reproducible at 2 ng/ml. The proposed method was successfully applied to study the pharmacokinetics of spironolactone and its major metabolite in healthy male Chinese volunteers. PMID:16541392

  11. HPLC/MS analysis of polyphenols, antioxidant and antimicrobial activities of Artabotrys hildebrandtii O. Hffm. extracts.

    PubMed

    Andriamadio, Julio Hervé; Rasoanaivo, Léa Herilala; Benedec, Daniela; Vlase, Laurian; Gheldiu, Ana-Maria; Duma, Mihaela; Toiu, Anca; Raharisololalao, Amélie; Oniga, Ilioara

    2015-01-01

    The purpose of this work was to evaluate chemical constituents, antioxidant and antimicrobial activities of Artabotrys hildebrandtii, an endemic medicinal plant from Madagascar. Ethanol extracts from the leaves and stem bark were tested to evaluate DPPH free radical scavenging, using butylated hydroxytoluene and quercetin as standard antioxidants. An high-performance liquid chromatography/mass spectrometry method was developed to investigate the presence of phenolic compounds in the studied samples; gentisic acid, chlorogenic acid, hyperoside, isoquercitrin, rutin, quercitrin, quercetol, apigenin and luteolin were identified. Total polyphenolic content was determined by a spectrophotometric method using Folin-Ciocâlteu reagent. Results showed the efficiency of A. hildebrandtii leaves extract against strains of Staphylococcus aureus and Listeria monocytogenes, as the inhibitory activity is more powerful compared to Gentamicin, used as the standard drug. The leaves of A. hildebrandtii can be considered an important source of polyphenols, especially of rutin, with good antioxidant and antimicrobial activities.

  12. LC-MS Guided Isolation of Bioactive Principles from Iris hookeriana and Bioevaluation of Isolates for Antimicrobial and Antioxidant Activities.

    PubMed

    Dar, B A; Lone, S H; Shah, W A; Bhat, K A

    2016-08-01

    The genus Iris is diverse both in the abundance of secondary metabolities as well as the biological activities. The rhizomes of Iris hookeriana exhibit significant anthelminthic activity against gastrointestinal nematodes of sheep. Although Iris hookeriana has been a subject of the study of so many phytochemical studies, yet we report some constituents for the first time from this plant using a different isolation approach. This manuscript presents the isolation, antimicrobial and antioxidant evaluation of bioactive principles from Iris hookeriana. LC-MS guided isolation technique was applied for the separation of target constituents. The isolates were characterised by spectral techniques and subjected to antioxidant evaluation by DPPH assay. Four compounds; resveratrol, resveratroloside, junipeginin C and isorhamnetin-3-O-neohesperidoside were isolated for the first time along with 3 known compounds viz piceid, irigenin and iridin from I. hookeriana using this approach. The antioxidant activity screening of the isolates revealed that all the 4 constituents isolated for the first time, have strong antioxidant potential with IC50 of 14.0 µg/ml (resveratroloside), 19.7 µg/ml (junipeginen C), 12.8 µg/ml (resveratrol) and 19.8 µg/ml (isorhamnetin-3-O-neohesperodoside). So it can be safely concluded that LC-MS guided isolation of chemical compounds from Iris hookeriana has furnished 4 antioxidant constituents. Thus Iris hookeriana can act as as a good source of wonder molecule resveratrol and its 2 glycosides, resveratrolside and piceid which upon hydrolysis can be converted into the parent drug resveratrol. PMID:27281447

  13. Fast simultaneous LC/MS/MS determination of 10 active compounds in human serum for therapeutic drug monitoring in psychiatric medication.

    PubMed

    Sistik, Pavel; Urinovska, Romana; Brozmanova, Hana; Kacirova, Ivana; Silhan, Petr; Lemr, Karel

    2016-02-01

    A UPLC/MS/MS method with simple protein precipitation has been validated for the fast simultaneous analysis of agomelatine, asenapine, amisulpride, iloperidone, zotepine, melperone, ziprasidone, vilazodone, aripiprazole and its metabolite dehydro-aripiprazole in human serum. Alprenolol was applied as an internal standard. A BEH C18 (2.1 × 50 mm, 1.7 µm) column provided chromatographic separation of analytes using a binary mobile phase gradient (A, 2 mmol/L ammonium acetate, 0.1% formic acid in 5% acetonitrile, v/v/v; B, 2 mmol/L ammonium acetate, 0.1% formic acid in 95% acetonitrile, v/v/v). Mass spectrometric detection was performed in the positive electrospray ionization mode and ion suppression owing to matrix effects was evaluated. The validation criteria were determined: linearity, precision, accuracy, recovery, limit of detection, limit of quantification, reproducibility and matrix effect. The concentration range was as follows: 0.25-1000 ng/mL for agomelatine; 0.25-100 ng/mL for asenapine and iloperidone; 2.5-1000 ng/mL for amisulpride, aripiprazole, vilazodone and zotepine; 2.3-924.6 ng/mL for dehydroaripiprazole; 2.2-878.4 ng/mL for melperone; and 2.2-883.5 ng/mL for ziprasidone. Limits of quantitation below a therapeutic reference range were achieved for all analytes. Intra-run precision of 0.4-5.5 %, inter-run precision of 0.6-8.2% and overall recovery of 87.9-114.1% were obtained. The validated method was successfully implemented into routine practice for therapeutic drug monitoring in our hospital. PMID:26094602

  14. Simultaneous quantification of vortioxetine, carvedilol and its active metabolite 4-hydroxyphenyl carvedilol in rat plasma by UPLC-MS/MS: Application to their pharmacokinetic interaction study.

    PubMed

    Huang, Yi; Zheng, Shuangli; Pan, Yongyang; Li, Tao; Xu, Zhi-Sheng; Shao, Meng-Meng

    2016-09-01

    To establish a rapid and sensitive ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the determination of vortioxetine, carvedilol and its metabolite 4-hydroxyphenyl carvedilol in rat plasma. The analytes and the internal standard (diazepam) were separated on an Acquity UPLC BEH C18 chromatography column (2.1mm×50mm, 1.7μm) using gradient elution with a mobile phase of acetonitrile and 0.1% formic acid in water at a flow rate of 0.4mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode to monitor the precursor-to-product ion transitions of m/z 299.2→150.1 for vortioxetine, m/z 407.2→100.3 for carvedilol, m/z 423.2→100.1 for 4-hydroxyphenyl carvedilol and m/z 285.2→193.1 for diazepam (IS) using a positive electrospray ionization interface. The method was validated over a concentration range of 0.5-100ng/mL for vortioxetine, 0.5-1000ng/mL for carvedilol and 0.1-50ng/mL for 4-hydroxyphenyl carvedilol. Total time for each chromatograph was 3.0min. The intra- and inter-day precision and accuracy of the quality control samples at low, medium, and high concentration levels exhibited relative standard deviations (RSD)<11.6% and the accuracy values ranged from -12.2% to 11.3%. The analytical method was successfully applied to a pharmacokinetic interaction study of vortioxetine and carvedilol after oral administration vortioxetine and carvedilol in rats. Results suggested that the co-administration of vortioxetine and carvedilol results in a significant drug interaction in rats. PMID:27262994

  15. Anti-acetylcholinesterase and antioxidant activities and HPLC-MS analysis of polyphenol from extracts of Nelsonia canescens (Lam.) Spreng.

    PubMed Central

    Ouattara, Nabèrè; Meda, Roland Nâg-Tiero; Hilou, Adama; Guenné, Samson; Konaté, Kiessoum; Coulibaly, Ahmed Y; Kiendrébeogo, Martin; Millogo, Jeanne F; Nacoulma, Odile G

    2013-01-01

    Objective To investigate the anti-acetylcholinesterase and antioxidant activities and to evaluate the major polyphenolic compounds of Nelsonia canescens extracts. Methods The anti-acetylcholinesterase activity was assessed using a kinetic inhibition standard method. Two methods, ABTS and lipid peroxidation, were used to estimate the antioxidant capacity. Polyphenols profile of the plant extract has been determined with a HPLC-MS method. Results The results showed that butanol extract exhibited the best anti-acetylcholinesterase activity with inhibition percentage of (55.62±1.49)%. The best 3 ethylbenzothiazoline-6-sulphonate radical cation scavenging capacity was found for ethyl acetate extract with a value of (56.20±0.77) mg equivalent trolox/g while the crude extract showed the highest inhibition of the rat liver lipid peroxidation (52.57±1.20)%. Polyphenols profile revealed the presence of five phenol acids (p-coumaric acid, caffeic acid, chlorogenic acid, ferulic acid and gentisic acid) and three flavonoids (apigenin, luteolin, quercetin). Conclusions All the extracts of Nelsonia canescens exhibited antioxidant and AChE inhibition capacities. The active compounds identified and quantified in this species are mainly responsible for these in vitro biological activities and allow to justify its widely use in Burkina Faso traditional medicine.

  16. Copper-induced activation of TRP channels promotes extracellular calcium entry, activation of CaMs and CDPKs, copper entry and membrane depolarization in Ulva compressa

    PubMed Central

    Gómez, Melissa; González, Alberto; Sáez, Claudio A.; Morales, Bernardo; Moenne, Alejandra

    2015-01-01

    In order to identify channels involved in membrane depolarization, Ulva compressa was incubated with agonists of TRP channels C5, A1 and V1, and the level of intracellular calcium was detected. Agonists of TRPC5, A1 and V1 induced increases in intracellular calcium at 4, 9, and 11 min of exposure, respectively, and antagonists of TRPC5, A1, and V1 corresponding to SKF-96365 (SKF), HC-030031 (HC), and capsazepin (CPZ), respectively, inhibited calcium increases indicating that functional TRPs exist in U. compressa. In addition, copper excess induced increases in intracellular calcium at 4, 9, and 12 min which were inhibited by SKF, HC, and CPZ, respectively, indicating that copper activate TRPC5, A1, and V1 channels. Moreover, copper-induced calcium increases were inhibited by EGTA, a non-permeable calcium chelating agent, but not by thapsigargin, an inhibitor of endoplasmic reticulum (ER) calcium ATPase, indicating that activation of TRPs leads to extracellular calcium entry. Furthermore, copper-induced calcium increases were not inhibited by W-7, an inhibitor of CaMs, and staurosporine, an inhibitor of CDPKs, indicating that extracellular calcium entry did not require activation of CaMs and CDPKs. In addition, copper induced membrane depolarization events at 4, 8, and 11 min and these events were inhibited by SKF, HC, CPZ, and bathocuproine, a specific copper chelating agent, indicating that copper entry through TRP channels leads to membrane depolarization. Moreover, membrane depolarization events were inhibited by W-7 and staurosporine, indicating that activation of CaMs and CDPKs is required to allow copper entry through TRPs. Interestingly, copper-induced calcium increases and depolarization events were light-dependent and were inhibited by DCMU, an inhibitor of photosystem II, and ATP-γ-S, a non-hydrolizable analog of ATP, suggesting that ATP derived from photosynthesis is required to activate TRPs. Thus, light-dependent copper-induced activation TRPC5, A1

  17. Multiple sclerosis. Oligodendrocyte survival and proliferation in an active established lesion.

    PubMed

    Raine, C S; Scheinberg, L; Waltz, J M

    1981-12-01

    Oligodendrocytes have been studied ultrastructurally in relationship to areas of active demyelination in multiple sclerosis. The tissue came from a central nervous system plaque sampled at biopsy during a neurosurgical procedure to correct severe intention tremor in a case of chronic progressive multiple sclerosis. Cells interpreted as oligodendrocytes were abundant within the demyelinated zone, were easily identifiable, and sometimes occurred as nests of cells suggestive of proliferation. Oligodendrocytes were also common within areas of active demyelination where numerous macrophages displayed active phagocytosis of myelin. These oligodendrocytes were paler and perhaps represented residual, surviving cells. In the relatively normal white matter adjacent to the plaque, increased numbers of oligodendrocytes occurred in association with remyelination. In the demyelinated zone, the astrocyte:macrophage:oligodendrocyte ratio was 1:2.25:4.5; within the region of ongoing demyelination, 1:4:4; and in the adjacent white matter, 1:0.1:2.1. On the basis of an apparent proliferation and survival of oligodendrocytes, the findings support the notions that there is no selective depletion of oligodendrocytes either during or shortly following central nervous system demyelination in multiple sclerosis, and that the myelin sheath is the primary target. PMID:7321526

  18. Distinct spatial activation of intrinsic and extrinsic apoptosis pathways in natural scrapie: association with prion-related lesions

    PubMed Central

    Serrano, Carmen; Lyahyai, Jaber; Bolea, Rosa; Varona, Luis; Monleón, Eva; Badiola, Juan J.; Zaragoza, Pilar; Martín-Burriel, Inmaculada

    2009-01-01

    Neurodegeneration and gliosis are the main neuropathological features of prion diseases. However, the molecular mechanisms involved in these processes remain unclear. Several studies have demonstrated changes in the expression of apoptotic factors and inflammatory cytokines in animals with experimental infection. Here we present the expression profiles of 15 genes implicated in the intrinsic and extrinsic apoptotic pathways in the central nervous systems of sheep naturally infected with scrapie. Expression changes obtained by real-time RT-PCR were also compared with the extent of classical scrapie lesions, such as prion deposition, neuronal vacuolisation, spongiosis, and astrogliosis as well as with the activation of caspase-3, using a stepwise regression. The results suggest that the factors assessed participate in apoptotic or inflammatory functions, depending on the affected area. The mitochondrial apoptosis pathway was associated with prion deposition in the prefrontal cortex (the less affected area), and with activation of caspase-3-mediated cell death via over-expression of BAK. In addition to its known association with astroglial activation, the extrinsic apoptosis pathway was also related to cell death and neuronal vacuolisation. PMID:19401142

  19. a Computational Model for Lesion Dynamics in Multiple Sclerosis of the Brain

    NASA Astrophysics Data System (ADS)

    Mohan, T. R. Krishna; Sen, Surajit; Ramanathan, Murali

    Multiple sclerosis (MS) is a chronic disabling disease of the central nervous system (CNS) that is characterized by lesions with inflammatory cells, axons with the insulating myelin sheath damaged, and axonal loss. The causes of MS are not known and there is as yet no cure. The purpose of this research was to evaluate a physically motivated network model for lesion formation in the brain. The parsimonious network model contained two elements: (i) a spatially spreading pathological process causing cell damage and death leading to neuro-degeneration and, (ii) generation of alarm signals by the damaged cells that lead to activation of programmed death of cells surrounding the lesions in an attempt to contain the spatial spread of the pathologic process. Simulation results with a range of network geometries indicated that the model was capable of describing lesion progression and arrest. The modeling results also demonstrated dynamical complexity with sensitivity to initial conditions.

  20. In Vitro Antibacterial, Antioxidant, and Cytotoxic Activities of Parthenium hysterophorus and Characterization of Extracts by LC-MS Analysis

    PubMed Central

    Kumar, Shashank; Pandey, Sanjay; Pandey, Abhay K.

    2014-01-01

    Present work reports the biological activities of P. hysterophorus leaf, stem, flower, and root. Dried samples were sequentially extracted with many solvents. Hexane (HX), benzene (BZ), and chloroform (CH) extracts of leaf showed considerable antibacterial activity against Streptococcus mutans (MTCC 497), Proteus vulgaris (MTCC 7299), and Salmonella typhi (MTCC 3917). Flower extracts exhibited presence of higher amount of flavonoids (13.9–59.6 μgQE/mg) followed by leaf, stem, and root. Stem (HX, BZ, and CH), leaf ethanol (ET), and root (HX, BZ, and CH) fractions showed noticeable antioxidant capacity in phosphomolybdate assay. Most of the extracts demonstrated beta carotene bleaching inhibition capability. BZ, ethyl acetate (EA), and ET fractions of leaves, stem aqueous (AQ), and flower EA extracts showed membrane protective activities (40–55%). Middle fractions of the plant parts displayed moderate antihemolytic potential. Most of the flower extracts exhibited cytotoxic activity (80–100%) against lung and colon cancer cell lines. Root (HX and ET) and leaf ET extracts showed considerable inhibition (90–99%) of colon and ovary cancer cell lines. The LC-MS scan demonstrated presence of different compounds showing 3–20 min retention time. The study revealed considerable antibacterial, antioxidant, lipo-protective, antihemolytic, and anticancer potential in all parts of P. hysterophorus. PMID:24895583

  1. Active fault mapping in Karonga-Malawi after the December 19, 2009 Ms 6.2 seismic event

    NASA Astrophysics Data System (ADS)

    Macheyeki, A. S.; Mdala, H.; Chapola, L. S.; Manhiça, V. J.; Chisambi, J.; Feitio, P.; Ayele, A.; Barongo, J.; Ferdinand, R. W.; Ogubazghi, G.; Goitom, B.; Hlatywayo, J. D.; Kianji, G. K.; Marobhe, I.; Mulowezi, A.; Mutamina, D.; Mwano, J. M.; Shumba, B.; Tumwikirize, I.

    2015-02-01

    The East African Rift System (EARS) has natural hazards - earthquakes, volcanic eruptions, and landslides along the faulted margins, and in response to ground shaking. Strong damaging earthquakes have been occurring in the region along the EARS throughout historical time, example being the 7.4 (Ms) of December 1910. The most recent damaging earthquake is the Karonga earthquake in Malawi, which occurred on 19th December, 2009 with a magnitude of 6.2 (Ms). The earthquake claimed four lives and destroyed over 5000 houses. In its effort to improve seismic hazard assessment in the region, Eastern and Southern Africa Seismological Working Group (ESARSWG) under the sponsorship of the International Program on Physical Sciences (IPPS) carried out a study on active fault mapping in the region. The fieldwork employed geological and geophysical techniques. The geophysical techniques employed are ground magnetic, seismic refraction and resistivity surveys but are reported elsewhere. This article gives findings from geological techniques. The geological techniques aimed primarily at mapping of active faults in the area in order to delineate presence or absence of fault segments. Results show that the Karonga fault (the Karonga fault here referred to as the fault that ruptured to the surface following the 6th-19th December 2009 earthquake events in the Karonga area) is about 9 km long and dominated by dip slip faulting with dextral and insignificant sinistral components and it is made up of 3-4 segments of length 2-3 km. The segments are characterized by both left and right steps. Although field mapping show only 9 km of surface rupture, maximum vertical offset of about 43 cm imply that the surface rupture was in little excess of 14 km that corresponds with Mw = 6.4. We recommend the use or integration of multidisciplinary techniques in order to better understand the fault history, mechanism and other behavior of the fault/s for better urban planning in the area.

  2. A randomized trial to evaluate the effect of a trace mineral premix on the incidence of active digital dermatitis lesions in cattle.

    PubMed

    Gomez, A; Bernardoni, N; Rieman, J; Dusick, A; Hartshorn, R; Read, D H; Socha, M T; Cook, N B; Döpfer, D

    2014-10-01

    A balanced, parallel-group, single-blinded randomized efficacy study divided into 2 periods was conducted to evaluate the effect of a premix containing higher than typically recommended levels of organic trace minerals and iodine (HOTMI) in reducing the incidence of active digital dermatitis (DD) lesions acquired naturally and induced by an experimental infection challenge model. For the natural exposure phase of the study, 120 healthy Holstein steers 5 to 7 mo of age without signs of hoof disease were randomized into 2 groups of 60 animals. The control group was fed a standard trace mineral supplement and the treatment group was fed the HOTMI premix, both for a period of 60 d. On d 60, 15 steers free of macroscopic DD lesions were randomly selected from each group for the challenge phase and transported to an experimental facility, where they were acclimated and then challenged within a DD infection model. The same diet group allocation was maintained during the 60 d of the challenge phase. The primary outcome measured was the development of an active DD lesion greater than 20mm in diameter across its largest dimension. No lesions were identified during the natural exposure phase. During the challenge phase, 55% (11/20) and 30% (6/20) of feet were diagnosed with an active DD lesion in the control and treatment groups, respectively. Diagnosis of DD was confirmed by histopathologic demonstration of invasive Treponema spp. within eroded and hyperplastic epidermis and ulcerated papillary dermis. All DD confirmed lesions had dark-field microscopic features compatible with DD and were positive for Treponema spp. by PCR. As a secondary outcome, the average DD lesion size observed in all feet was also evaluated. Overall mean (standard deviation) lesion size was 17.1 (2.36) mm and 11.1 (3.33) mm for the control and treatment groups, respectively, with this difference being driven by acute DD lesions >20mm. A trend existed for the HOTMI premix to reduce the total DD

  3. Targetable Kinase-Activating Lesions in Ph-like Acute Lymphoblastic Leukemia

    PubMed Central

    Roberts, K.G.; Li, Y.; Payne-Turner, D.; Harvey, R.C.; Yang, Y.-L.; Pei, D.; McCastlain, K.; Ding, L.; Lu, C.; Song, G.; Ma, J.; Becksfort, J.; Rusch, M.; Chen, S.-C.; Easton, J.; Cheng, J.; Boggs, K.; Santiago-Morales, N.; Iacobucci, I.; Fulton, R.S.; Wen, J.; Valentine, M.; Cheng, C.; Paugh, S.W.; Devidas, M.; Chen, I-M.; Reshmi, S.; Smith, A.; Hedlund, E.; Gupta, P.; Nagahawatte, P.; Wu, G.; Chen, X.; Yergeau, D.; Vadodaria, B.; Mulder, H.; Winick, N.J.; Larsen, E.C.; Carroll, W.L.; Heerema, N.A.; Carroll, A.J.; Grayson, G.; Tasian, S.K.; Moore, A.S.; Keller, F.; Frei-Jones, M.; Whitlock, J.A.; Raetz, E.A.; White, D.L.; Hughes, T.P.; Auvil, J.M. Guidry; Smith, M.A.; Marcucci, G.; Bloomfield, C.D.; Mrózek, K.; Kohlschmidt, J.; Stock, W.; Kornblau, S.M.; Konopleva, M.; Paietta, E.; Pui, C.-H.; Jeha, S.; Relling, M.V.; Evans, W.E.; Gerhard, D.S.; Gastier-Foster, J.M.; Mardis, E.; Wilson, R.K.; Loh, M.L.; Downing, J.R.; Hunger, S.P.; Willman, C.L.; Zhang, J.; Mullighan, C.G.

    2014-01-01

    BACKGROUND Philadelphia chromosome–like acute lymphoblastic leukemia (Ph-like ALL) is characterized by a gene-expression profile similar to that of BCR–ABL1–positive ALL, alterations of lymphoid transcription factor genes, and a poor outcome. The frequency and spectrum of genetic alterations in Ph-like ALL and its responsiveness to tyrosine kinase inhibition are undefined, especially in adolescents and adults. METHODS We performed genomic profiling of 1725 patients with precursor B-cell ALL and detailed genomic analysis of 154 patients with Ph-like ALL. We examined the functional effects of fusion proteins and the efficacy of tyrosine kinase inhibitors in mouse pre-B cells and xenografts of human Ph-like ALL. RESULTS Ph-like ALL increased in frequency from 10% among children with standard-risk ALL to 27% among young adults with ALL and was associated with a poor outcome. Kinase-activating alterations were identified in 91% of patients with Ph-like ALL; rearrangements involving ABL1, ABL2, CRLF2, CSF1R, EPOR, JAK2, NTRK3, PDGFRB, PTK2B, TSLP, or TYK2 and sequence mutations involving FLT3, IL7R, or SH2B3 were most common. Expression of ABL1, ABL2, CSF1R, JAK2, and PDGFRB fusions resulted in cytokine-independent proliferation and activation of phosphorylated STAT5. Cell lines and human leukemic cells expressing ABL1, ABL2, CSF1R, and PDGFRB fusions were sensitive in vitro to dasatinib, EPOR and JAK2 rearrangements were sensitive to ruxolitinib, and the ETV6–NTRK3 fusion was sensitive to crizotinib. CONCLUSIONS Ph-like ALL was found to be characterized by a range of genomic alterations that activate a limited number of signaling pathways, all of which may be amenable to inhibition with approved tyrosine kinase inhibitors. Trials identifying Ph-like ALL are needed to assess whether adding tyrosine kinase inhibitors to current therapy will improve the survival of patients with this type of leukemia. (Funded by the American Lebanese Syrian Associated Charities and

  4. Electromyographic identification of spinal oscillator patterns and recouplings in a patient with incomplete spinal cord lesion: oscillator formation training as a method to improve motor activities.

    PubMed

    Schalow, G; Blanc, Y; Jeltsch, W; Zäch, G A

    1996-08-01

    A patient with a strongly lesioned spinal cord, sub C5, relearned running, besides improving other movements, by an oscillator formation training (rhythmic, dynamic, stereotyped exercise). After 45 days of jumping on a springboard and other rhythm trainings, the patient was able to run 90 m in 41 s (7.9 km/h) (even 9.3 km/h 3 years after the lesion) besides marching (5.7 km/h), cycling, playing tennis and skiing. FF-type (alpha 1) (f = 8.3-11.4 Hz) and FR-type (alpha 2) (f = 6.7 Hz) motor unit firings were identified by electromyography (EMG) with surface electrodes by their oscillatory firing patterns in this patient. In EMG literature, the alpha 2-oscillatory firing is called "myokymic discharging". Alternating long and short oscillation periods were measured in FF-type motor units, with changing focus (change from long/short to short/long oscillation periods). The alternating mean period durations differed by approximately 10 ms. Transient synchronization of oscillatory firing FF-type motor units was observed with up to two phase relations per oscillation cycle. In recumbent position, the phase change in synchronization of two oscillatory firing motor units in the soleus muscle of one leg correlated with the change from alternating to symmetrical oscillatory firing of a third motor unit in the soleus muscle of the other leg. This measurement indicates that the alternating oscillatory firing of premotor neuronal networks is correlated with synchronization of oscillatory firing neuronal subnetworks, i.e., with coupling changes of oscillators, and is not due to reciprocal inhibition of half-centre oscillators as suggested by the change from alternating to symmetrical oscillatory firing. Coupling changes of oscillatory firing subnetworks to generate macroscopic (integrative) network functions are therefore a general organization form of the central nervous system (CNS), and are not related to rhythmic movements like walking or running only. It is proposed that

  5. [Osteoarticular lesions from parachuting].

    PubMed

    Orso, C A; Valbonesi, L; Calabrese, B F; D'Onofrio, S

    1990-01-01

    Based on personal experience gained in a parachuting centre (Pescara Aero-club) from 1975 up to 1988, the authors report their evaluation on chronic and acute osteoarticular lesions. The review of the cases was not based on the incidence of the lesions nor on their characteristics, normally found in common traumatology, but it was related to the dynamics of the trauma during the landing and to painful syndromes following a prolonged parachuting activity.

  6. Studies of intestinal lymphoid tissue. VII. The secondary nature of lymphoid cell "activation" in the jejunal lesion of tropical sprue.

    PubMed

    Marsh, M N; Mathan, M; Mathan, V I

    1983-09-01

    Morphometric techniques were used in the evaluation of lymphocyte morphology and activity in tropical sprue. jejunal biopsies from control subjects (8), patients with epidemic disease (7), patients with endemic disease (11), and subjects who had recovered from sprue (4) were analyzed blindly. In patients with sprue, lymphocytes were increased significantly within crypt (but not surface) epithelium. Immunoblasts (greater than 6 mu in diameter) were increased by 5% over control subjects. Group means for lymphocytic mitotic indexes were also significantly raised, while flux ratios only differed significantly between endemic sprue patients and control subjects. The lymphocytic infiltration was distributed focally in the upper crypt and crypt-villus interzones. Analysis of epidemic cases (presenting within 4-28 days) revealed detectable changes in lymphocyte behavior only after 3 weeks' illness, whereas mucosal lesions and malabsorption were already established during the first week. These data indicate that lymphocyte activation, suggestive of a local cell-mediated immune reaction, does occur in tropical sprue but is secondary to damage already inflicted on enterocytes and their function.

  7. Studies of intestinal lymphoid tissue. VII. The secondary nature of lymphoid cell "activation" in the jejunal lesion of tropical sprue.

    PubMed Central

    Marsh, M. N.; Mathan, M.; Mathan, V. I.

    1983-01-01

    Morphometric techniques were used in the evaluation of lymphocyte morphology and activity in tropical sprue. jejunal biopsies from control subjects (8), patients with epidemic disease (7), patients with endemic disease (11), and subjects who had recovered from sprue (4) were analyzed blindly. In patients with sprue, lymphocytes were increased significantly within crypt (but not surface) epithelium. Immunoblasts (greater than 6 mu in diameter) were increased by 5% over control subjects. Group means for lymphocytic mitotic indexes were also significantly raised, while flux ratios only differed significantly between endemic sprue patients and control subjects. The lymphocytic infiltration was distributed focally in the upper crypt and crypt-villus interzones. Analysis of epidemic cases (presenting within 4-28 days) revealed detectable changes in lymphocyte behavior only after 3 weeks' illness, whereas mucosal lesions and malabsorption were already established during the first week. These data indicate that lymphocyte activation, suggestive of a local cell-mediated immune reaction, does occur in tropical sprue but is secondary to damage already inflicted on enterocytes and their function. Images Figure 3 Figure 4 Figure 5 PMID:6614143

  8. Antinociceptive activity of the HPLC- and MS-standardized hydroethanolic extract of Pterodon emarginatus Vogel leaves.

    PubMed

    Negri, Giuseppina; Mattei, Rita; Mendes, Fúlvio Rieli

    2014-01-01

    Several studies have demonstrated the analgesic and anti-inflammatory effects of fruit and seed extracts from Pterodon emarginatus Vogel (Fabaceae). The objective of this study was to evaluate the antinociceptive activity of the hydroethanolic extract of P. emarginatus leaves in mice and characterize its chemical composition using HPLC coupled to UV-vis diode array detection and mass spectrometry with electrospray ionization. Our results showed that the doses of 500 and 1000 mg/kg produced an antinociceptive effect, as observed in the hot plate test and writhing induced by acetic acid. The chromatographic profile and spectral mass data suggest the presence of di-C-glycosylflavones (e.g., vicenin-2 and schaftoside), C,O-glycosylflavones (e.g., chrysoeriol-8-C-glucosyl-2″-O-glucuronide-6-C-arabinoside) and luteolin-7-O-rutinoside as the main constituents. Lower levels of oleanane-type saponins, such as soyasaponin Bb and Be, and the saponin derivatives hederagenin and aglycone B, which are typical of Fabaceae family, were also found. From this study, it is suggested that the analgesic effect observed is not due to the terpenoids previously reported from fruit and seed extracts, but could be attributed to flavones and the hederagenin derivatives that were identified as main constituents of the hydroethanolic extract from the leaves.

  9. Cooperative control of two active spacecraft during proximity operations. M.S. Thesis - MIT

    NASA Technical Reports Server (NTRS)

    Polutchko, Robert J.

    1989-01-01

    A cooperative autopilot is developed for the control of the relative attitude, relative position and absolute attitude of two maneuvering spacecraft during on orbit proximity operations. The autopilot consists of an open-loop trajectory solver which computes a nine dimensional linearized nominal state trajectory at the beginning of each maneuver and a phase space regulator which maintains the two spacecraft on the nominal trajectory during coast phases of the maneuver. A linear programming algorithm is used to perform jet selection. Simulation tests using a system of two space shuttle vehicles are performed to verify the performance of the cooperative controller and comparisons are made to a traditional passive target/active pursuit vehicle approach to proximity operations. The cooperative autopilot is shown to be able to control the two vehicle system when both the would be pursuit vehicle and the target vehicle are not completely controllable in six degrees of freedom. The cooperative controller is also shown to use as much as 37 percent less fuel and 57 percent fewer jet firings than a single pursuit vehicle during a simple docking approach maneuver.

  10. Active control of the forced and transient response of a finite beam. M.S. Thesis

    NASA Technical Reports Server (NTRS)

    Post, John T.

    1990-01-01

    Structural vibrations from a point force are modelled on a finite beam. This research explores the theoretical limit on controlling beam vibrations utilizing another point source as an active controller. Three different types of excitation are considered, harmonic, random, and transient. For harmonic excitation, control over the entire beam length is possible only when the excitation frequency is near a resonant frequency of the beam. Control over a subregion may be obtained even between resonant frequencies at the cost of increasing the vibration outside of the control region. For random excitation, integrating the expected value of the displacement squared over the required interval, is shown to yield the identical cost function as obtained by integrating the cost function for harmonic excitation over all excitation frequencies. As a result, it is always possible to reduce the cost function for random excitation whether controlling the entire beam or just a subregion, without ever increasing the vibration outside the region in which control is desired. The last type of excitation considered is a single, transient pulse. The form of the controller is specified as either one or two delayed pulses, thus constraining the controller to be casual. The best possible control is examined while varying the region of control and the controller location. It is found that control is always possible using either one or two control pulses.

  11. Vascular Lesions.

    PubMed

    Jahnke, Marla N

    2016-08-01

    Vascular lesions in childhood are comprised of vascular tumors and vascular malformations. Vascular tumors encompass neoplasms of the vascular system, of which infantile hemangiomas (IHs) are the most common. Vascular malformations, on the other hand, consist of lesions due to anomalous development of the vascular system, including the capillary, venous, arterial, and lymphatic systems. Capillary malformations represent the most frequent type of vascular malformation. IHs and vascular malformations tend to follow relatively predictable growth patterns in that IHs grow then involute during early childhood, whereas vascular malformations tend to exhibit little change. Both vascular tumors and vascular malformations can demonstrate a wide range of severity and potential associated complications necessitating specialist intervention when appropriate. Evaluation and treatment of the most common types of vascular lesions are discussed in this article. [Pediatr Ann. 2016;45(8):e299-e305.]. PMID:27517358

  12. Active Control of the Forced and Transient Response of a Finite Beam. M.S. Thesis

    NASA Technical Reports Server (NTRS)

    Post, John Theodore

    1989-01-01

    When studying structural vibrations resulting from a concentrated source, many structures may be modelled as a finite beam excited by a point source. The theoretical limit on cancelling the resulting beam vibrations by utilizing another point source as an active controller is explored. Three different types of excitation are considered, harmonic, random, and transient. In each case, a cost function is defined and minimized for numerous parameter variations. For the case of harmonic excitation, the cost function is obtained by integrating the mean squared displacement over a region of the beam in which control is desired. A controller is then found to minimize this cost function in the control interval. The control interval and controller location are continuously varied for several frequencies of excitation. The results show that control over the entire beam length is possible only when the excitation frequency is near a resonant frequency of the beam, but control over a subregion may be obtained even between resonant frequencies at the cost of increasing the vibration outside of the control region. For random excitation, the cost function is realized by integrating the expected value of the displacement squared over the interval of the beam in which control is desired. This is shown to yield the identical cost function as obtained by integrating the cost function for harmonic excitation over all excitation frequencies. As a result, it is always possible to reduce the cost function for random excitation whether controlling the entire beam or just a subregion, without ever increasing the vibration outside the region in which control is desired. The last type of excitation considered is a single, transient pulse. A cost function representative of the beam vibration is obtained by integrating the transient displacement squared over a region of the beam and over all time. The form of the controller is chosen a priori as either one or two delayed pulses. Delays

  13. Object knowledge during entry-level categorization is activated and modified by implicit memory after 200 ms.

    PubMed

    Schendan, Haline E; Maher, Stephen M

    2009-02-15

    The timing of activating memory about visual objects is important for theories of human cognition but largely unknown, especially for tasks like entry level categorization that activate semantic memory. We tested an implicit memory-categorization "equivalence" hypothesis of multiple memory systems theory that a cortical system that stores structural knowledge to support entry level categorization also stores long-term, perceptual implicit memory, resulting in priming of this knowledge. Event-related brain potentials (ERPs) were recorded to impoverished pictures of new and repeated objects that were similar in perceptual properties but differed in categorization success. The cortical dynamics of object knowledge were defined using categorization ratings and naming. As predicted, rating, naming, and repetition effects on a frontocentral N350 show that implicit memory modifies the object knowledge network supporting categorization. This ERP is a complex of components between 200 and 500 ms indexing temporally overlapping substates from more perceptual to more conceptual knowledge. A frontopolar N350 subcomponent defines the first substate of a process of object model selection from occipitotemporal cortex based on shape similarity, and indicates that implicit memory in this system is greater with better categorization success. Afterwards, parietal positivity and a slow wave index secondary, post-model selection processes, like evaluating the success of a decision or memory match, and working memory for overt report, respectively. Altogether, ERP findings support the equivalence hypothesis and a two-state interactive account of visual object knowledge, and delineate the timing of multiple memory systems.

  14. In vitro anti-oxidative activities of the various parts of Parkia biglobosa and GC-MS analysis of extracts with high activity.

    PubMed

    Ibrahim, M A; Koorbanally, N A; Islam, M S

    2013-01-01

    The anti-oxidative activities of sequentially extracted solvent fractions of different parts of P. biglobosa were evaluated in a series of in vitro assays. Our findings indicated that all extracts had electron donating and free radical scavenging activities. But the ethanol (EtOH) extracts from all the parts demonstrated more promising anti-oxidative effects in these experimental models. Apart from the aqueous extracts of the stem bark and leaves, all other extracts exhibited hydroxyl radical scavenging (HRS) activity but the ethyl acetate (EtOAc) extract of the stem bark and EtOH extracts of the root and leaves possessed more powerful HRS activity than other corresponding extracts in the parts. Further, nitric oxide (NO) inhibition activities were observed in all the extracts except the EtOAc extract of the stem bark which showed pro-oxidative activity. However, the EtOH extract of the stem bark and root as well as the EtOAc extract of the leaves displayed more potent anti-NO activity than other extracts in the parts. The GC-MS analysis of the EtOH extracts revealed that the most abundant phytochemicals are pyrogallol derivatives. Data from this study suggest that the EtOH extracts from different parts of P. biglobosa contained potent anti-oxidative agents and pyrogallol could be the main bioactive constituent.

  15. Successful Nonoperative Management of HAGL (Humeral Avulsion of Glenohumeral Ligament) Lesion With Concurrent Axillary Nerve Injury in an Active-Duty US Navy SEAL.

    PubMed

    Ernat, Justin J; Bottoni, Craig R; Rowles, Douglas J

    2016-01-01

    Humeral avulsion of the glenohumeral ligament (HAGL) is a lesion that has been recognized as a cause of recurrent shoulder instability. To our knowledge there are no reports of successful return to full function in young, competitive athletes or return to manual labor following nonoperative management of a HAGL lesion. A 26-year-old Navy SEAL was diagnosed with a HAGL injury, and associated traction injury of the axillary nerve as well as a partial tear of the rotator cuff. Operative intervention was recommended; however, due to issues with training and with inability to properly rehab with the axillary nerve injury, surgical plans were delayed. Interestingly, the patient demonstrated both clinical and radiographic magnetic resonance imaging healing of his lesion over an 18-month period. At 18 months the patient had returned to full active duty without pain or instability as a Navy SEAL. PMID:27552458

  16. HPLC-DAD-MS/MS profiling of standardized rosemary extract and enhancement of its anti-wrinkle activity by encapsulation in elastic nanovesicles.

    PubMed

    Ezzat, Shahira M; Salama, Maha M; ElMeshad, Aliaa N; Teaima, Mahmoud H; Rashad, Laila A

    2016-07-01

    The anti-wrinkle activity of defatted rosemary extract (DER) was assessed, and its effect was optimized by encapsulation in transferosomes (TFs). DER was standardized to a rosmarinic acid content of 4.58 ± 0.023 mg% using reversed-phase high performance liquid chromatography (Rp-HPLC), and its components were identified by HPLC-diode array detection-tandem mass spectrometry. In vitro free radical scavenging assays showed DER had high free radical scavenging activity against 2,2-diphenyl-2-picryl hydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), and superoxide radicals. DER also inhibited bleaching of β-carotene with high Fe(III) and Fe(II) chelating ability. In vivo anti-wrinkle activities of topically applied DER (20, 50, and 100 mg) and a TF formulation (TF4, 20 mg of DER) were evaluated in UVB-irradiated mice using a wrinkle scoring method, metalloproteinase (MMP) expression, and histopathology. Among the nanovesicles, TF4 was the most deformable, and had an acceptable size and encapsulation efficiency and enhanced permeation of DER through rat skin compared with unencapsulated DER. DER (50 and 100 mg) and TF4 significantly inhibited MMP-2 and MMP-9 expression and improved wrinkle scores. DER and TF4 moderately decreased epidermal thickness without pigmentation. DER is a potent natural antioxidant for combating skin aging. Moreover, encapsulation of DER in TFs will enhance its skin permeation and anti-wrinkle activity. PMID:27107862

  17. HPLC-DAD-MS/MS profiling of standardized rosemary extract and enhancement of its anti-wrinkle activity by encapsulation in elastic nanovesicles.

    PubMed

    Ezzat, Shahira M; Salama, Maha M; ElMeshad, Aliaa N; Teaima, Mahmoud H; Rashad, Laila A

    2016-07-01

    The anti-wrinkle activity of defatted rosemary extract (DER) was assessed, and its effect was optimized by encapsulation in transferosomes (TFs). DER was standardized to a rosmarinic acid content of 4.58 ± 0.023 mg% using reversed-phase high performance liquid chromatography (Rp-HPLC), and its components were identified by HPLC-diode array detection-tandem mass spectrometry. In vitro free radical scavenging assays showed DER had high free radical scavenging activity against 2,2-diphenyl-2-picryl hydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), and superoxide radicals. DER also inhibited bleaching of β-carotene with high Fe(III) and Fe(II) chelating ability. In vivo anti-wrinkle activities of topically applied DER (20, 50, and 100 mg) and a TF formulation (TF4, 20 mg of DER) were evaluated in UVB-irradiated mice using a wrinkle scoring method, metalloproteinase (MMP) expression, and histopathology. Among the nanovesicles, TF4 was the most deformable, and had an acceptable size and encapsulation efficiency and enhanced permeation of DER through rat skin compared with unencapsulated DER. DER (50 and 100 mg) and TF4 significantly inhibited MMP-2 and MMP-9 expression and improved wrinkle scores. DER and TF4 moderately decreased epidermal thickness without pigmentation. DER is a potent natural antioxidant for combating skin aging. Moreover, encapsulation of DER in TFs will enhance its skin permeation and anti-wrinkle activity.

  18. Peroxisome-proliferator activator receptor-gamma activation decreases attachment of endometrial cells to peritoneal mesothelial cells in an in vitro model of the early endometriotic lesion.

    PubMed

    Kavoussi, S K; Witz, C A; Binkley, P A; Nair, A S; Lebovic, D I

    2009-10-01

    The aim of this study was to investigate whether peroxisome proliferator-activated receptor (PPAR)-gamma activation has an effect on the attachment of endometrial cells to peritoneal mesothelial cells in a well-established in vitro model of the early endometriotic lesion. The endometrial epithelial cell line EM42 and mesothelial cell line LP9 were used for this study. EM42 cells, LP9 cells or both were treated with the PPAR-gamma agonist ciglitazone (CTZ) at varying concentrations (10, 20 and 40 microM) x 48 h with subsequent co-culture of EM42 and LP9 cells. The rate of EM42 attachment and invasion through LP9 cells was then assessed and compared with control (EM42 and LP9 cells co-cultured without prior treatment with CTZ). Next, attachment of CTZ-treated and untreated EM42 cells to hyaluronic acid (HA), a cell adhesion molecule (CAM) on peritoneal mesothelial cells, were assessed. Although there was no difference in EM42 attachment when LP9 cells alone were treated with CTZ, treatment of EM42 cells with 40 microM CTZ decreased EM42 attachment to LP9 cells by 27% (P < 0.01). Treatment of both EM42 and LP9 cells with 40 microM CTZ decreased EM42 attachment to LP9 by 37% (P < 0.01). Treatment of EM42 cells with 40 microM CTZ decreased attachment to HA by 66% (P = 0.056). CTZ did not decrease invasion of EM42 cells through the LP9 monolayer. CTZ may inhibit EM42 cell proliferation. In conclusion, CTZ significantly decreased EM42 attachment to LP9 cells and HA in an in vitro model of the early endometriotic lesion. PMID:19643817

  19. Assessment of biological activity and UPLC–MS based chromatographic profiling of ethanolic extract of Ochradenus arabicus

    PubMed Central

    Ali, M. Ajmal; Farah, M. Abul; Al-Hemaid, Fahad M.; Abou-Tarboush, Faisal M.; Al-Anazi, Khaled M.; Wabaidur, S.M.; Alothman, Z.A.; Lee, Joongku

    2015-01-01

    Natural products from wild and medicinal plants, either in the form of crude extracts or pure compounds provide unlimited opportunities for new drug leads owing to the unmatched availability of chemical diversity. In the present study, the cytotoxic potential of crude ethanolic extract of Ochradenus arabicus was analyzed by MTT cell viability assay in MCF-7 adenocarcinoma breast cancer cells. We further investigated its effect against oxidative stress induced by anticancer drug doxorubicin. In addition, Ultra Performance Liquid Chromatography–Mass Spectrometry (UPLC–MS) based chromatographic profiling of crude extract of O. arabicus was performed. The MTT assay data showed that the extract is moderately toxic to the MCF-7 cells. However, its treatment alone does not induce oxidative stress while doxorubicin increases the level of oxidative stress in MCF-7 cells. Whereas, simultaneous treatment of plant extract and doxorubicin significantly (p < 0.05) decreased the level of intracellular reactive oxygen species (ROS) and lipid peroxidation while an increase in the reduced glutathione and superoxide dismutase activity was observed in time and dose dependent manner. Hence, our finding confirmed cytotoxic and antioxidant potential of crude extract of O. arabicus in MCF-7 cells. However, further investigations on O. arabicus as a potential chemotherapeutic agent are needed. The analysis of bioactive compounds present in the plant extracts involving the applications of common phytochemical screening assays such as chromatographic techniques is discussed. PMID:26981004

  20. [GC-MS analysis and cytotoxic activity of the supercritical extracts from roots and stems of Zanthoxylum nitidum].

    PubMed

    He, Zi-Ning; Liu, Jia-Wei; Li, Wu-Guo; Sima, Zhen-Hua; Chen, Wei-Wen

    2014-02-01

    The volatile components of roots and stems of Zanthoxylum nitidum were investigated by supercritical fluid carbon dioxide extraction (SFE-CO2) and gas chromatography-mass spectrometry(GC-MS). Thirty-one and fifty-one compounds were identified in the supercritical extracts from roots and stems of Z. nitidum, respectively, and total twenty-seven compounds were the common constituents. Among them, the major constituents in root and stem supercritical extracts were spathulenol (18.49 and 26.18%), n-hexadecanoic acid (14.24% and 12.79%), ar-tumerone (6.95% and 8.88%), oleic acid (8.39% and 5.71%) and hexanoic acid (4.39% and 7.78%). The in-vitro MTT assay showed that the volatile components of roots and stems of Z. nitidum did not exhibited any cytotoxic activity against human cancer Huh-7 and normal IEC-6 cells. These results indicated the same nature of the volatile constituents in the root and stem of Z. nitidum. This investigation may provide further evidence for expansion of medicinal parts of Z. nitidum.

  1. Immunoadjuvant activity, toxicity assays, and determination by UPLC/Q-TOF-MS of triterpenic saponins from Chenopodium quinoa seeds.

    PubMed

    Verza, Simone G; Silveira, Fernando; Cibulski, Samuel; Kaiser, Samuel; Ferreira, Fernando; Gosmann, Grace; Roehe, Paulo M; Ortega, George G

    2012-03-28

    The adjuvant activity of Chenopodium quinoa (quinoa) saponins on the humoral and cellular immune responses of mice subcutaneously immunized with ovalbumin (OVA) was evaluated. Two quinoa saponin fractions were obtained, FQ70 and FQ90, and 10 saponins were determined by UPLC/Q-TOF-MS. Mice were immunized subcutaneously with OVA alone or adjuvanted with Quil A (adjuvant control), FQ70, or FQ90. FQ70 and FQ90 significantly enhanced the amount of anti-OVA-specific antibodies in serum (IgG, IgG1, and IgG2b) in immunized mice. The adjuvant effect of FQ70 was significantly greater than that of FQ90. However, delayed type hypersensitivity responses were higher in mice immunized with OVA adjuvanted with FQ90 than mice treated with FQ70. Concanavalin A (Con A)-, lipopolysaccharide-, and OVA-stimulated splenocyte proliferation were measured, and FQ90 significantly enhanced the Con A-induced splenocyte proliferation. The results suggested that the two quinoa saponin fractions enhanced significantly the production of humoral and cellular immune responses to OVA in mice.

  2. Use of ICP/MS with ultrasonic nebulizer for routine determination of uranium activity ratios in natural water

    USGS Publications Warehouse

    Kraemer, T.F.; Doughten, M.W.; Bullen, T.D.

    2002-01-01

    A method is described that allows precise determination of 234U/238U activity ratios (UAR) in most natural waters using commonly available inductively coupled plasma/mass spectrometry (ICP/MS) instrumentation and accessories. The precision achieved by this technique (??0.5% RSD, 1 sigma) is intermediate between thermal ionization mass spectrometry (??0.25% RSID, 1 sigma) and alpha particle spectrometry (??5% RSD, 1 sigma). It is precise and rapid enough to allow analysis of a large number of samples in a short period of time at low cost using standard, commercially available quadrupole instrumentation with ultrasonic nebulizer and desolvator accessories. UARs have been analyzed successfully in fresh to moderately saline waters with U concentrations of from less than 1 ??g/L to nearly 100 ??g/L. An example of the uses of these data is shown for a study of surface-water mixing in the North Platte River in western Nebraska. This rapid and easy technique should encourage the wider use of uranium isotopes in surface-water and groundwater investigations, both for qualitative (e.g. identifying sources of water) and quantitative (e.g. determining end-member mixing ratios purposes.

  3. Enhanced photocatalytic H2-production activity of CdxZn1-xS nanocrystals by surface loading MS (M = Ni, Co, Cu) species

    NASA Astrophysics Data System (ADS)

    Wang, Jian; Li, Bo; Chen, Jiazang; Li, Na; Zheng, Jianfeng; Zhao, Jianghong; Zhu, Zhenping

    2012-10-01

    To investigate the role of metal sulfides as co-catalyst for photocatalytic hydrogen production under visible light irradiation, we have loaded small amounts of transition-metal sulfides (MS), such as NiS, CoS and CuS, onto the surface of CdxZn1-xS solid solution. It can be found that the rate of H2 evolution over the MS/Cd0.4Zn0.6S was 5 times higher than that of the pure Cd0.4Zn0.6S, and is comparable to the Cd0.4Zn0.6S modified with 1 wt% platinum (Pt) co-catalysts. The MS/Cd0.4Zn0.6S photocatalysts were characterized by X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), UV-visible spectrophotometer (UV-vis), and photoluminescence (PL) spectroscopy. It can be speculated that the MS provided active sites for H2 production and caused the migration of excited electrons from Cd0.4Zn0.6S toward MS, leading to the enhancement of photocatalytic activity.

  4. Review: DNA oxidation, its consequences and efficacy of GC-MS and SPME-GC-MS for In Vitro quantification of DNA oxidative products

    NASA Astrophysics Data System (ADS)

    Singh, Himansha; Udawat, Abhishek; Franklin, Tony; Sarathi, Sai Partha

    2012-10-01

    DNA oxidation could be one of the main factors contributing to DNA damage, eventually leading to carcinogenesis, mutations or non-carcinogenic diseases such as Parkinsonís and Alzheimerís. Only recently has the focus turned towards identifying oxidative products of DNA and their consequences. Metabolism activities in vitro produce reactive radicals, which can break DNA strands to cause lesions. These lesions could also act as biomarkers for diagnostic purposes. This review provides an insight of the DNA oxidation mechanism, its harmful consequences and the advantages/disadvantages of available techniques to quantify such DNA oxidative products, focussing mainly on the use GC-MS along with derivatization reaction. In addition, the review also discusses the use of Solid Phase Micro Extraction (SPME) before conducting GC-MS as a potential assay to overcome the discrepancies involved in using GC-MS alone for the identification of DNA oxidative products.

  5. Simultaneous analysis of 11 main active components in Cirsium setosum based on HPLC-ESI-MS/MS and combined with statistical methods.

    PubMed

    Sun, Qian; Chang, Lu; Ren, Yanping; Cao, Liang; Sun, Yingguang; Du, Yingfeng; Shi, Xiaowei; Wang, Qiao; Zhang, Lantong

    2012-11-01

    A novel method based on high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry was developed for simultaneous determination of the 11 major active components including ten flavonoids and one phenolic acid in Cirsium setosum. Separation was performed on a reversed-phase C(18) column with gradient elution of methanol and 0.1‰ acetic acid (v/v). The identification and quantification of the analytes were achieved on a hybrid quadrupole linear ion trap mass spectrometer. Multiple-reaction monitoring scanning was employed for quantification with switching electrospray ion source polarity between positive and negative modes in a single run. Full validation of the assay was carried out including linearity, precision, accuracy, stability, limits of detection and quantification. The results demonstrated that the method developed was reliable, rapid, and specific. The 25 batches of C. setosum samples from different sources were first determined using the developed method and the total contents of 11 analytes ranged from 1717.460 to 23028.258 μg/g. Among them, the content of linarin was highest, and its mean value was 7340.967 μg/g. Principal component analysis and hierarchical clustering analysis were performed to differentiate and classify the samples, which is helpful for comprehensive evaluation of the quality of C. setosum.

  6. Simultaneous quantification of cryptotanshinone and its active metabolite tanshinone IIA in plasma by liquid chromatography/tandem mass spectrometry (LC-MS/MS).

    PubMed

    Hao, Haiping; Wang, Guangji; Li, Peng; Li, Jing; Ding, Zuoqi

    2006-02-13

    A rapid and sensitive method for the simultaneous determination of cryptotanshinone and its active metabolite tanshinone IIA in rat plasma was developed and well validated, using high-performance liquid chromatographic separation with tandem mass spectrometric detection. This method entailed a single step of liquid-liquid extraction with ethyl acetate from a small volume of plasmas. The analytes and internal standard diazepam were baseline separated on a Shim-pack VP-ODS analytical column. Detection was performed on a triple quadrupole tandem mass spectrometer equipped with electrospray ionization source operated under selected reaction monitoring (SRM) mode. The method was linear in the concentration range of 1-100 ng/ml for both tanshinone IIA and cryptotanshinone. The intra- and inter-day precisions (R.S.D.%) were within 10.2% for both analytes. Deviation of the assay accuracies was within +/-12.0% for both analytes. Both analytes were proved to be stable during all sample storing, preparation and analytic procedures. The method was successfully applied to a pharmacokinetic study after an oral administration of cryptotanshinone to rats with a dose of 20 mg/kg. With the lower limits of quantification at 1.0 ng/ml for tanshinone IIA and 0.2 ng/ml for cryptotanshinone, this method was proved to be sensitive enough and reproducible for the pharmacokinetics study of both tanshinones. PMID:16169701

  7. Challenges and solutions in the bioanalysis of BMS-986094 and its metabolites including a highly polar, active nucleoside triphosphate in plasma and tissues using LC-MS/MS.

    PubMed

    Liu, Ang; Lute, John; Gu, Huidong; Wang, Bonnie; Trouba, Kevin J; Arnold, Mark E; Aubry, Anne-Françoise; Wang, Jian

    2015-09-01

    BMS-986094, a nucleotide polymerase inhibitor of the hepatitis C virus, was withdrawn from clinical trials because of a serious safety issue. To investigate a potential association between drug/metabolite exposure and toxicity in evaluations conducted after the termination of the BMS-986094 development program, it was essential to determine the levels of BMS-986094 and its major metabolites INX-08032, INX-08144 and INX-09054 in circulation and the active nucleoside triphosphate INX-09114 in target and non-target tissues. However, there were many challenges in the bioanalysis of these compounds. The chromatography challenge for the extremely polar nucleoside triphosphate was solved by applying mixed-mode chromatography which combined anion exchange and reversed-phase interactions. The LC conditions provided adequate retention and good peak shape of the analyte and showed good robustness. A strategy using simultaneous extraction but separate LC analysis of the prodrug BMS-986094 and its major circulating metabolites was used to overcome a carryover issue of the hydrophobic prodrug while still achieving good chromatography of the polar metabolites. In addition, the nucleotide analytes were not stable in the presence of endogenous enzymes. Low pH and low temperature were required for blood collection and plasma sample processing. However, the use of phosphatase inhibitor and immediate homogenization and extraction were critical for the quantitative analysis of the active triphosphate, INX-09114, in tissue samples. To alleviate the bioanalytical complexity caused by multiple analytes, different matrices, and various species, a fit-for-purpose approach to assay validation was implemented based on the needs of drug safety assessment in non-clinical (GLP or non-GLP) studies. The assay for INX-08032 was fully validated in plasma of toxicology species. The lower limit of quantification was 1.00ng/mL and the linear curve range was 1.00-500.00ng/mL using a weighted (1/x(2

  8. Challenges and solutions in the bioanalysis of BMS-986094 and its metabolites including a highly polar, active nucleoside triphosphate in plasma and tissues using LC-MS/MS.

    PubMed

    Liu, Ang; Lute, John; Gu, Huidong; Wang, Bonnie; Trouba, Kevin J; Arnold, Mark E; Aubry, Anne-Françoise; Wang, Jian

    2015-09-01

    BMS-986094, a nucleotide polymerase inhibitor of the hepatitis C virus, was withdrawn from clinical trials because of a serious safety issue. To investigate a potential association between drug/metabolite exposure and toxicity in evaluations conducted after the termination of the BMS-986094 development program, it was essential to determine the levels of BMS-986094 and its major metabolites INX-08032, INX-08144 and INX-09054 in circulation and the active nucleoside triphosphate INX-09114 in target and non-target tissues. However, there were many challenges in the bioanalysis of these compounds. The chromatography challenge for the extremely polar nucleoside triphosphate was solved by applying mixed-mode chromatography which combined anion exchange and reversed-phase interactions. The LC conditions provided adequate retention and good peak shape of the analyte and showed good robustness. A strategy using simultaneous extraction but separate LC analysis of the prodrug BMS-986094 and its major circulating metabolites was used to overcome a carryover issue of the hydrophobic prodrug while still achieving good chromatography of the polar metabolites. In addition, the nucleotide analytes were not stable in the presence of endogenous enzymes. Low pH and low temperature were required for blood collection and plasma sample processing. However, the use of phosphatase inhibitor and immediate homogenization and extraction were critical for the quantitative analysis of the active triphosphate, INX-09114, in tissue samples. To alleviate the bioanalytical complexity caused by multiple analytes, different matrices, and various species, a fit-for-purpose approach to assay validation was implemented based on the needs of drug safety assessment in non-clinical (GLP or non-GLP) studies. The assay for INX-08032 was fully validated in plasma of toxicology species. The lower limit of quantification was 1.00ng/mL and the linear curve range was 1.00-500.00ng/mL using a weighted (1/x(2

  9. UPLC-MS-MS method for simultaneous determination of caffeine, tolbutamide, metoprolol, and dapsone in rat plasma and its application to cytochrome P450 activity study in rats.

    PubMed

    Liu, Yan; Li, Xiang; Yang, Chunjuan; Tai, Sheng; Zhang, Xiangning; Liu, Gaofeng

    2013-01-01

    A specific ultra-performance liquid chromatography tandem mass spectrometry method has been described for the simultaneous determination of caffeine, tolbutamide, metoprolol and dapsone in rat plasma, which are the four probe drugs of the four cytochrome P450 (CYP450) isoforms CYP1A2, CYP2C9, CYP2D6 and CYP3A4. The chromatographic separation was achieved using a Waters Acquity UPLC BEH HILIC C(18) column (2.1 × 50 mm, 1.7 µm). The mobile phase consisted of acetonitrile and water (containing 0.1% formic acid) (15:85, v/v). The triple quadrupole mass spectrometric detection was operated by positive electrospray ionization. Phenacetin was chosen as internal standard. Plasma samples were extracted with dichloromethane-butanol (10:1, v/v). The recoveries ranged from 67.5% to 98.5%. The calibration curves in plasma were linear in the range of 2.5-1,000 ng/mL for caffeine and dapsone, 5-5,000 ng/mL for tolbutamide and 2.5-250 ng/mLfor metoprolol, with correlation coefficient (r(2)) of 0.9936, 0.9966, 0.9990 and 0.9998, respectively. The method was successfully applied to pharmacokinetic studies of the four probe drugs of the four CYP450 isoforms and used to evaluate the effects of breviscapine on the activities of CYP1A2, CYP2C9, CYP2D6 and CYP3A4 in rats.

  10. Elevated thymidine phosphorylase activity in psoriatic lesions accounts for the apparent presence of an epidermal growth inhibitor, but is not in itself growth inhibitory

    SciTech Connect

    Hammerberg, C.; Fisher, G.J.; Voorhees, J.J.; Cooper, K.D. )

    1991-08-01

    An apparent tissue-specific growth inhibitor, or chalone, obtained from psoriatic lesions was tentatively identified in the 100-kDa fraction based upon inhibition of DNA synthesis, as measured by (3H)-thymidine uptake by a squamous cell carcinoma cell line, SCC 38. This fraction, however, failed to inhibit SCC 38 cell growth when assessed directly in a neutral red uptake assay. Characterization of the inhibitor of (3H)-thymidine uptake revealed it to have biochemical properties identical to thymidine phosphorylase: (1) molecular weight close to 100 kDa, (2) isoelectric point of 4.2, and (3) thymidine phosphorylase enzyme activity. Thus, the authors conclude that its ability to inhibit (3H)-thymidine uptake was due to thymidine catabolism rather than inhibition of DNA synthesis or growth inhibition. Examination of thymidine phosphorylase activity in keratome biopsies from psoriatic and normal skin demonstrated a twentyfold increase in activity in psoriatic lesions relative to non-lesional or normal skin. This increase in metabolism of thymidine was due to thymidine phosphorylase rather than uridine phosphorylase activity. The correlation between increased thymidine phosphorylase activity and increased keratinocyte proliferation in vitro (cultured) and in vivo (psoriasis), suggests that this enzyme may play a critical role in providing the thymidine necessary for keratinocyte proliferation.

  11. MS Detectors

    SciTech Connect

    Koppenaal, David W.; Barinaga, Charles J.; Denton, M Bonner B.; Sperline, Roger P.; Hieftje, Gary M.; Schilling, G. D.; Andrade, Francisco J.; Barnes IV., James H.

    2005-11-01

    Good eyesight is often taken for granted, a situation that everyone appreciates once vision begins to fade with age. New eyeglasses or contact lenses are traditional ways to improve vision, but recent new technology, i.e. LASIK laser eye surgery, provides a new and exciting means for marked vision restoration and improvement. In mass spectrometry, detectors are the 'eyes' of the MS instrument. These 'eyes' have also been taken for granted. New detectors and new technologies are likewise needed to correct, improve, and extend ion detection and hence, our 'chemical vision'. The purpose of this report is to review and assess current MS detector technology and to provide a glimpse towards future detector technologies. It is hoped that the report will also serve to motivate interest, prompt ideas, and inspire new visions for ion detection research.

  12. The effects of electrical stimulation or an electrolytic lesion in the mediodorsal thalamus of the rat on survival, body weight, food intake and running activity in the activity-based anorexia model.

    PubMed

    Luyten, Laura; Welkenhuysen, Marleen; van Kuyck, Kris; Fieuws, Steffen; Das, John; Sciot, Raf; Nuttin, Bart

    2009-04-29

    The glucose metabolism in the mediodorsal thalamus (MD) is increased in rats in the activity-based anorexia (ABA) model. In patients, electrical stimulation in hyperactive brain regions reduced symptoms in e.g. major depressive disorder and cluster headache. In two blinded randomised controlled experiments, we therefore examined the effects of high-frequency electrical stimulation and an electrolytic lesion in the MD in a validated rat model for anorexia nervosa. The ABA model was successfully replicated in all our experiments, with a reduction in body weight, food intake, and survival time and an increase in running activity. In a first experiment, we evaluated the effect of electrical stimulation or a curative lesion in the MD on survival, body weight, food intake and locomotor activity in ABA rats. Electrical MD stimulation or an electrolytic MD lesion did not improve the symptoms of rats in the ABA model, compared to control groups. In a second experiment, we investigated the effect of a preventive electrolytic lesion in the MD on rats in the ABA model. Although there was no significant improvement of survival, body weight and food intake, locomotor activity was significantly reduced in the lesion group compared to the control group. Apart from this positive effect on running activity, we found no convincing evidence for the suitability of the MD as a neuromodulation target for anorexia nervosa patients.

  13. Analysis of Immune Response Markers in Jorge Lobo's Disease Lesions Suggests the Occurrence of Mixed T Helper Responses with the Dominance of Regulatory T Cell Activity.

    PubMed

    Azevedo, Michelle de C S; Rosa, Patricia S; Soares, Cleverson T; Fachin, Luciana R V; Baptista, Ida Maria F D; Woods, William J; Garlet, Gustavo P; Trombone, Ana Paula F; Belone, Andrea de F F

    2015-01-01

    Jorge Lobo's disease (JLD) is a chronic infection that affects the skin and subcutaneous tissues. Its etiologic agent is the fungus Lacazia loboi. Lesions are classified as localized, multifocal, or disseminated, depending on their location. Early diagnosis and the surgical removal of lesions are the best therapeutic options currently available for JLD. The few studies that evaluate the immunological response of JLD patients show a predominance of Th2 response, as well as a high frequency of TGF-β and IL-10 positive cells in the lesions; however, the overall immunological status of the lesions in terms of their T cell phenotype has yet to be determined. Therefore, the objective of this study was to evaluate the pattern of Th1, Th2, Th17 and regulatory T cell (Treg) markers mRNA in JLD patients by means of real-time PCR. Biopsies of JLD lesions (N = 102) were classified according to their clinical and histopathological features and then analyzed using real-time PCR in order to determine the expression levels of TGF-β1, FoxP3, CTLA4, IKZF2, IL-10, T-bet, IFN-γ, GATA3, IL-4, IL-5, IL-13, IL-33, RORC, IL-17A, IL-17F, and IL-22 and to compare these levels to those of healthy control skin (N = 12). The results showed an increased expression of FoxP3, CTLA4, TGF-β1, IL-10, T-bet, IL-17F, and IL-17A in lesions, while GATA3 and IL-4 levels were found to be lower in diseased skin than in the control group. When the clinical forms were compared, TGF-β1 was found to be highly expressed in patients with a single localized lesion while IL-5 and IL-17A levels were higher in patients with multiple/disseminated lesions. These results demonstrate the occurrence of mixed T helper responses and suggest the dominance of regulatory T cell activity, which could inhibit Th-dependent protective responses to intracellular fungi such as L. loboi. Therefore, Tregs may play a key role in JLD pathogenesis. PMID:26700881

  14. Analysis of Immune Response Markers in Jorge Lobo's Disease Lesions Suggests the Occurrence of Mixed T Helper Responses with the Dominance of Regulatory T Cell Activity

    PubMed Central

    Azevedo, Michelle de C. S.; Rosa, Patricia S.; Soares, Cleverson T.; Fachin, Luciana R. V.; Baptista, Ida Maria F. D.; Woods, William J.; Garlet, Gustavo P.

    2015-01-01

    Jorge Lobo’s disease (JLD) is a chronic infection that affects the skin and subcutaneous tissues. Its etiologic agent is the fungus Lacazia loboi. Lesions are classified as localized, multifocal, or disseminated, depending on their location. Early diagnosis and the surgical removal of lesions are the best therapeutic options currently available for JLD. The few studies that evaluate the immunological response of JLD patients show a predominance of Th2 response, as well as a high frequency of TGF-β and IL-10 positive cells in the lesions; however, the overall immunological status of the lesions in terms of their T cell phenotype has yet to be determined. Therefore, the objective of this study was to evaluate the pattern of Th1, Th2, Th17 and regulatory T cell (Treg) markers mRNA in JLD patients by means of real-time PCR. Biopsies of JLD lesions (N = 102) were classified according to their clinical and histopathological features and then analyzed using real-time PCR in order to determine the expression levels of TGF-β1, FoxP3, CTLA4, IKZF2, IL-10, T-bet, IFN-γ, GATA3, IL-4, IL-5, IL-13, IL-33, RORC, IL-17A, IL-17F, and IL-22 and to compare these levels to those of healthy control skin (N = 12). The results showed an increased expression of FoxP3, CTLA4, TGF-β1, IL-10, T-bet, IL-17F, and IL-17A in lesions, while GATA3 and IL-4 levels were found to be lower in diseased skin than in the control group. When the clinical forms were compared, TGF-β1 was found to be highly expressed in patients with a single localized lesion while IL-5 and IL-17A levels were higher in patients with multiple/disseminated lesions. These results demonstrate the occurrence of mixed T helper responses and suggest the dominance of regulatory T cell activity, which could inhibit Th-dependent protective responses to intracellular fungi such as L. loboi. Therefore, Tregs may play a key role in JLD pathogenesis. PMID:26700881

  15. Analysis of Immune Response Markers in Jorge Lobo's Disease Lesions Suggests the Occurrence of Mixed T Helper Responses with the Dominance of Regulatory T Cell Activity.

    PubMed

    Azevedo, Michelle de C S; Rosa, Patricia S; Soares, Cleverson T; Fachin, Luciana R V; Baptista, Ida Maria F D; Woods, William J; Garlet, Gustavo P; Trombone, Ana Paula F; Belone, Andrea de F F

    2015-01-01

    Jorge Lobo's disease (JLD) is a chronic infection that affects the skin and subcutaneous tissues. Its etiologic agent is the fungus Lacazia loboi. Lesions are classified as localized, multifocal, or disseminated, depending on their location. Early diagnosis and the surgical removal of lesions are the best therapeutic options currently available for JLD. The few studies that evaluate the immunological response of JLD patients show a predominance of Th2 response, as well as a high frequency of TGF-β and IL-10 positive cells in the lesions; however, the overall immunological status of the lesions in terms of their T cell phenotype has yet to be determined. Therefore, the objective of this study was to evaluate the pattern of Th1, Th2, Th17 and regulatory T cell (Treg) markers mRNA in JLD patients by means of real-time PCR. Biopsies of JLD lesions (N = 102) were classified according to their clinical and histopathological features and then analyzed using real-time PCR in order to determine the expression levels of TGF-β1, FoxP3, CTLA4, IKZF2, IL-10, T-bet, IFN-γ, GATA3, IL-4, IL-5, IL-13, IL-33, RORC, IL-17A, IL-17F, and IL-22 and to compare these levels to those of healthy control skin (N = 12). The results showed an increased expression of FoxP3, CTLA4, TGF-β1, IL-10, T-bet, IL-17F, and IL-17A in lesions, while GATA3 and IL-4 levels were found to be lower in diseased skin than in the control group. When the clinical forms were compared, TGF-β1 was found to be highly expressed in patients with a single localized lesion while IL-5 and IL-17A levels were higher in patients with multiple/disseminated lesions. These results demonstrate the occurrence of mixed T helper responses and suggest the dominance of regulatory T cell activity, which could inhibit Th-dependent protective responses to intracellular fungi such as L. loboi. Therefore, Tregs may play a key role in JLD pathogenesis.

  16. Analysis of Non-Enzymatically Glycated Peptides: Neutral-Loss Triggered MS3 Versus Multi-Stage Activation Tandem Mass Spectrometry

    SciTech Connect

    Zhang, Qibin; Petyuk, Vladislav A.; Schepmoes, Athena A.; Orton, Daniel J.; Monroe, Matthew E.; Yang, Feng; Smith, Richard D.; Metz, Thomas O.

    2008-10-15

    Non-enzymatic glycation of tissue proteins has important implications in the development of complications of diabetes mellitus. While electron transfer dissociation (ETD) has been shown to outperform collision-induced dissociation (CID) in sequencing glycated peptides by tandem mass spectrometry, ETD instrumentation is not yet available in all laboratories. In this study, we evaluated different advanced CID techniques (i.e., neutral-loss triggered MS3 and multi-stage activation) during LC-MSn analyses of Amadori-modified peptides enriched from human serum glycated in vitro. During neutral-loss triggered MS3 experiments, MS3 scans triggered by neutral-losses of 3 H2O or 3 H2O + HCHO produced similar results in terms of glycated peptide identifications. However, neutral losses of 3 H2O resulted in significantly more glycated peptide identifications during multi-stage activation experiments. Overall, the multi-stage activation approach produced more glycated peptide identifications, while the neutral-loss triggered MS3 approach resulted in much higher specificity. Both techniques offer a viable alternative to ETD for identifying glycated peptides when that method is unavailable.

  17. Development of a comprehensive spectral library of sildenafil and related active analogues using LC-QTOF-MS and its application for screening counterfeit pharmaceuticals.

    PubMed

    Lee, Sooyeun; Ji, Dajeong; Park, Meejung; Chung, Kyu Hyuck

    2015-12-01

    The abuse or misuse of forged erectile-dysfunction drugs, containing phosphodiesterase type 5 inhibitors (e.g. sildenafil), is a serious issue globally. Therefore, the detection of sildenafil and related active analogues in counterfeit pharmaceuticals or the differentiation between counterfeit and authentic drugs has been performed with a variety of analytical techniques. Recently, a liquid chromatography-hybrid quadrupole time-of-flight mass spectrometry (LC-QTOF-MS)-based in-house library, consisting of accurate mass ion fragmentation information and retention times, was effectively applied to screen a large number of compounds in field of forensic toxicology. However, a comprehensive LC-QTOF-MS spectral library of sildenafil and related active analogues has not yet been reported. In the present study, a spectral library of 40 compounds of sildenafil and related analogues was developed with accurate mass spectra and retention times using LC-QTOF-MS, and applied to screen nine marketed counterfeit products. The in-house library successfully identified sildenafil, dimethylsildenafil, hydroxyhomosildenafil, demethylhongdenafil, pseudovardenafil and vardenafil in the samples. Our LC-QTOF-MS-based spectral library search is considered a powerful approach for identifying sildenafil and related active analogues in counterfeit pharmaceuticals.

  18. Low NKp30, NKp46 and NKG2D expression and reduced cytotoxic activity on NK cells in cervical cancer and precursor lesions

    PubMed Central

    2009-01-01

    Background Persistent high risk HPV infection can lead to cervical cancer, the second most common malignant tumor in women worldwide. NK cells play a crucial role against tumors and virus-infected cells through a fine balance between activating and inhibitory receptors. Expression of triggering receptors NKp30, NKp44, NKp46 and NKG2D on NK cells correlates with cytolytic activity against tumor cells, but these receptors have not been studied in cervical cancer and precursor lesions. The aim of the present work was to study NKp30, NKp46, NKG2D, NKp80 and 2B4 expression in NK cells from patients with cervical cancer and precursor lesions, in the context of HPV infection. Methods NKp30, NKp46, NKG2D, NKp80 and 2B4 expression was analyzed by flow cytometry on NK cells from 59 patients with cervical cancer and squamous intraepithelial lesions. NK cell cytotoxicity was evaluated in a 4 hour CFSE/7-AAD flow cytometry assay. HPV types were identified by PCR assays. Results We report here for the first time that NK cell-activating receptors NKp30 and NKp46 are significantly down-regulated in cervical cancer and high grade squamous intraepithelial lesion (HGSIL) patients. NCRs down-regulation correlated with low cytolytic activity, HPV-16 infection and clinical stage. NKG2D was also down-regulated in cervical cancer patients. Conclusion Our results suggest that NKp30, NKp46 and NKG2D down-regulation represent an evasion mechanism associated to low NK cell activity, HPV-16 infection and cervical cancer progression. PMID:19531227

  19. Variability Selected Low-Luminosity Active Galactic Nuclei in the 4 Ms Chandra Deep Field-South

    NASA Technical Reports Server (NTRS)

    Young, M.; Brandt, W. N.; Xue, Y. Q.; Paolillo, D. M.; Alexander, F. E.; Bauer, F. E.; Lehmer, B. D.; Luo, B.; Shemmer, O.; Schneider, D. P.; Vignail, C.

    2012-01-01

    The 4 Ms Chandra Deep Field-South (CDF-S) and other deep X-ray surveys have been highly effective at selecting active galactic nuclei (AGN). However, cosmologically distant low-luminosity AGN (LLAGN) have remained a challenge to identify due to significant contribution from the host galaxy. We identify long-term X ray variability (approx. month years, observed frame) in 20 of 92 CDF-S galaxies spanning redshifts approx equals 00.8 - 1.02 that do not meet other AGN selection criteria. We show that the observed variability cannot be explained by X-ray binary populations or ultraluminous X-ray sources, so the variability is most likely caused by accretion onto a supermassive black hole. The variable galaxies are not heavily obscured in general, with a stacked effective power-law photon index of Gamma(sub Stack) approx equals 1.93 +/- 0.13, and arc therefore likely LLAGN. The LLAGN tend to lie it factor of approx equal 6-89 below the extrapolated linear variability-luminosity relation measured for luminous AGN. This may he explained by their lower accretion rates. Variability-independent black-hole mass and accretion-rate estimates for variable galaxies show that they sample a significantly different black hole mass-accretion-rate space, with masses a factor of 2.4 lower and accretion rates a factor of 22.5 lower than variable luminous AGNs at the same redshift. We find that an empirical model based on a universal broken power-law power spectral density function, where the break frequency depends on SMBH mass and accretion rate, roughly reproduces the shape, but not the normalization, of the variability-luminosity trends measured for variable galaxies and more luminous AGNs.

  20. Physical mapping of the herpes simplex virus type 2 nuc- lesion affecting alkaline exonuclease activity by using herpes simplex virus type 1 deletion clones.

    PubMed

    Wathen, M W; Hay, J

    1984-07-01

    The nuc- lesion affecting alkaline exonuclease activity in the herpes simplex virus type 2 (HSV-2) mutant ts1348 had previously been mapped to the EcoRI-D restriction enzyme fragment of HSV-1. Eight clones with deletions representing most of HSV-1 EcoRI fragment D were selected with lambda gtWES hybrids. These clones were tested for their ability to rescue the alkaline exonuclease activity of HSV-2 nuc- ts1348 virus. The sequences colinear with the HSV-2 nuc- lesion were found to map between 0.169 and 0.174 map units on the HSV-1 Patton genome, representing an 0.8-kilobase-pair region that is 12.9 to 13.7 kilobase pairs from the left end of HSV-1 EcoRI fragment D.

  1. Are Articular Cartilage Lesions and Meniscus Tears Predictive of IKDC, KOOS, and Marx Activity Level Outcomes after ACL Reconstruction? A 6-Year Multicenter Cohort Study

    PubMed Central

    Cox, Charles L.; Huston, Laura J.; Dunn, Warren R.; Reinke, Emily K.; Nwosu, Samuel K.; Parker, Richard D.; Wright, Rick W.; Kaeding, Christopher C.; Marx, Robert G.; Amendola, Annunziata; McCarty, Eric C.; Wolf, Brian R.; Harrell, Frank E.; Spindler, Kurt P.

    2014-01-01

    Background Identifying risk factors for inferior outcomes after ACL reconstruction (ACLR) is important for prognosis and future treatment. The goal of this study was to determine whether articular cartilage and meniscal variables are predictive of 3 validated sports outcome instruments after ACLR. Hypothesis/Purpose We hypothesized that articular cartilage lesions and meniscus tears/treatment would be predictors of the IKDC, KOOS (all 5 subscales), and Marx activity level at 6 years following ACLR. Study Design Prospective cohort, Level 1 Methods Between 2002 and 2004, 1512 ACLR subjects were prospectively enrolled and followed longitudinally with the IKDC, KOOS, and Marx activity score completed at entry, 2, and 6 years. A logistic regression model was built incorporating variables from patient demographics, surgical technique, articular cartilage injuries, and meniscus tears/treatment to determine the predictors (risk factors) of IKDC, KOOS, and Marx at 6 years. Results We completed a minimum follow-up on 86% (1307/1512) of our cohort at 6 years. The cohort was 56% male, had a median age of 23 years at the time of enrollment, with 76% reporting a non-contact injury mechanism. Incidence of concomitant pathology at the time of surgery consisted of the following: articular cartilage (medial femoral condyle [MFC]-25%, lateral femoral condyle [LFC]-20%, medial tibial plateau [MTP]-6%, lateral tibial plateau [LTP]-12%, patella-20%, trochlear-9%) and meniscal (medial-38%, lateral-46%). Both articular cartilage lesions and meniscal tears were significant predictors of 6-year outcomes on IKDC and KOOS. Grade 3 or 4 articular cartilage lesions (excluding patella) significantly reduced IKDC and KOOS scores at 6 years. IKDC demonstrated worse outcomes with the presence of a grade 3-4 chondral lesion on the MFC, MTP, and LFC. Likewise, KOOS was negatively affected by cartilage injury. The sole significant predictor of reduced Marx activity was the presence of a grade 4 lesion

  2. Facilitation and nonfacilitation of active avoidance behavior of rats with septal lesions in the shuttle box and running wheel.

    PubMed

    Blatt, R C

    1976-07-01

    It was hypothesized that facilitation of avoidance performance of rats with septal lesions occurs only in tasks that punish responses having the same topography as the avoidance response, such as intertrial responses, or tasks that have aversive consequences for making the avoidance response, such as a brightly illuminated safe compartment. Twenty-eight male rats were trained in two shuttle box tasks, and 24 were trained in two running-wheel avoidance tasks under conditions of punishment or nonpunishment of intertrial responses. Rats with septal lesions performed better than control rats in both the shuttle box and the wheel tasks when intertrial responses were punished. When intertrial responding was not punished, experimental and control groups did not differ in avoidance performance. Avoidance performance of punished and unpunished rats with septal lesions did not differ from each other or from unpunished control rats in either wheel or shuttle box tasks. These results were discussed in the context of the species-specific defense reaction (SSDR) avoidance theory of Bolles. It was suggested that septal lesions interfere with the suppression of ineffective SSDRs.

  3. The formation of inflammatory demyelinated lesions in cerebral white matter

    PubMed Central

    Maggi, Pietro; Cummings Macri, Sheila M.; Gaitán, María I.; Leibovitch, Emily; Wholer, Jillian E; Knight, Heather L.; Ellis, Mary; Wu, Tianxia; Silva, Afonso C.; Massacesi, Luca; Jacobson, Steven; Westmoreland, Susan; Reich, Daniel S.

    2016-01-01

    Objective Vascular permeability and inflammatory demyelination are intimately linked in the brain, but what is their temporal relationship? We aimed to determine the radiological correlates of the earliest tissue changes accompanying demyelination in a primate model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE) in the common marmoset. Methods At 7 tesla MRI, T1 maps, proton density and T2-weighted images were acquired before and after EAE induction in 5 marmosets (every other week before lesions appeared, weekly thereafter). From scans before and after intravenous injection of contrast material, we measured the evolution of lesional blood-brain-barrier (BBB) permeability, comparing in vivo MRI to postmortem tissue examination. Results On average, BBB permeability increased 3.5 fold (p<0.0001) over the 4 weeks prior to lesion appearance. Permeability gradually decreased after lesion appearance, with attendant changes in the distribution of inflammatory cells (predominantly macrophages and microglia) and demyelination. On tissue analysis, we also identified small perivascular foci of microglia and T cells without blood-derived macrophages or demyelination. These foci had no visible MRI correlates, though permeability within the foci, but not outside, increased in the weeks before the animals died (p<0.0001). Interpretation This study provides compelling evidence that in marmoset EAE, which forms lesions strongly resembling those of MS, early changes in vascular permeability are associated with perivascular inflammatory cuffing and parenchymal microglial activation but precede the arrival of blood-derived monocytes that accompany demyelination. Prospective detection of transient permeability changes could afford an opportunity for early intervention to forestall tissue damage in newly forming lesions. PMID:25088017

  4. Bacillus subtilis subsp. subtilis CBMDC3f with antimicrobial activity against Gram-positive foodborne pathogenic bacteria: UV-MALDI-TOF MS analysis of its bioactive compounds.

    PubMed

    Torres, M J; Petroselli, G; Daz, M; Erra-Balsells, R; Audisio, M C

    2015-06-01

    In this work a new Bacillus sp. strain, isolated from honey, was characterized phylogenetically. Its antibacterial activity against three relevant foodborne pathogenic bacteria was studied; the main bioactive metabolites were analyzed using ultraviolet matrix assisted laser desorption-ionization mass spectrometry (UV-MALDI MS). Bacillus CBMDC3f was phylogenetically characterized as Bacillus subtilis subsp. subtilis after rRNA analysis of the 16S subunit and the gyrA gene (access codes Genbank JX120508 and JX120516, respectively). Its antibacterial potential was evaluated against Listeria monocytogenes (9 strains), B. cereus (3 strains) and Staphylococcus aureus ATCC29213. Its cell suspension and cell-free supernatant (CFS) exerted significant anti-Listeria and anti-S. aureus activities, while the lipopeptides fraction (LF) also showed anti-B. cereus effect. The UV-MALDI-MS analysis revealed surfactin, iturin and fengycin in the CFS, whereas surfactin predominated in the LF. The CFS from CBMDC3f contained surfactin, iturin and fengycin with four, two and four homologues per family, respectively, whereas four surfactin, one iturin and one fengycin homologues were identified in the LF. For some surfactin homologues, their UV-MALDI-TOF/TOF (MS/MS; Laser Induced Decomposition method, LID) spectra were also obtained. Mass spectrometry analysis contributed with relevant information about the type of lipopeptides that Bacillus strains can synthesize. From our results, surfactin would be the main metabolite responsible for the antibacterial effect. PMID:25820813

  5. Active Breathing Control in Combination With Ultrasound Imaging: A Feasibility Study of Image Guidance in Stereotactic Body Radiation Therapy of Liver Lesions

    SciTech Connect

    Bloemen-van Gurp, Esther; Meer, Skadi van der; Hendry, Janet; Buijsen, Jeroen; Visser, Peter; Fontanarosa, Davide; Lachaine, Martin; Lammering, Guido; Verhaegen, Frank

    2013-03-15

    Purpose: Accurate tumor positioning in stereotactic body radiation therapy (SBRT) of liver lesions is often hampered by motion and setup errors. We combined 3-dimensional ultrasound imaging (3DUS) and active breathing control (ABC) as an image guidance tool. Methods and Materials: We tested 3DUS image guidance in the SBRT treatment of liver lesions for 11 patients with 88 treatment fractions. In 5 patients, 3DUS imaging was combined with ABC. The uncertainties of US scanning and US image segmentation in liver lesions were determined with and without ABC. Results: In free breathing, the intraobserver variations were 1.4 mm in left-right (L-R), 1.6 mm in superior-inferior (S-I), and 1.3 mm anterior-posterior (A-P). and the interobserver variations were 1.6 mm (L-R), 2.8 mm (S-I), and 1.2 mm (A-P). The combined uncertainty of US scanning and matching (inter- and intraobserver) was 4 mm (1 SD). The combined uncertainty when ABC was used reduced by 1.7 mm in the S-I direction. For the L-R and A-P directions, no significant difference was observed. Conclusion: 3DUS imaging for IGRT of liver lesions is feasible, although using anatomic surrogates in the close vicinity of the lesion may be needed. ABC-based breath-hold in midventilation during 3DUS imaging can reduce the uncertainty of US-based 3D table shift correction.

  6. Dissociation Behavior of a TEMPO-Active Ester Cross-Linker for Peptide Structure Analysis by Free Radical Initiated Peptide Sequencing (FRIPS) in Negative ESI-MS

    NASA Astrophysics Data System (ADS)

    Hage, Christoph; Ihling, Christian H.; Götze, Michael; Schäfer, Mathias; Sinz, Andrea

    2016-07-01

    We have synthesized a homobifunctional amine-reactive cross-linking reagent, containing a TEMPO (2,2,6,6-tetramethylpiperidine-1-oxy) and a benzyl group (Bz), termed TEMPO-Bz-linker, to derive three-dimensional structural information of proteins. The aim for designing this novel cross-linker was to facilitate the mass spectrometric analysis of cross-linked products by free radical initiated peptide sequencing (FRIPS). In an initial study, we had investigated the fragmentation behavior of TEMPO-Bz-derivatized peptides upon collision activation in (+)-electrospray ionization collision-induced dissociation tandem mass spectrometry (ESI-CID-MS/MS) experiments. In addition to the homolytic NO-C bond cleavage FRIPS pathway delivering the desired odd-electron product ions, an alternative heterolytic NO-C bond cleavage, resulting in even-electron product ions mechanism was found to be relevant. The latter fragmentation route clearly depends on the protonation of the TEMPO-Bz-moiety itself, which motivated us to conduct (-)-ESI-MS, CID-MS/MS, and MS3 experiments of TEMPO-Bz-cross-linked peptides to further clarify the fragmentation behavior of TEMPO-Bz-peptide molecular ions. We show that the TEMPO-Bz-linker is highly beneficial for conducting FRIPS in negative ionization mode as the desired homolytic cleavage of the NO-C bond is the major fragmentation pathway. Based on characteristic fragments, the isomeric amino acids leucine and isoleucine could be discriminated. Interestingly, we observed pronounced amino acid side chain losses in cross-linked peptides if the cross-linked peptides contain a high number of acidic amino acids.

  7. Simultaneous determination of 2',3'-dideoxyinosine and the active metabolite, 2',3'-dideoxyadenosine-5'-triphosphate in human peripheral-blood mononuclear cell by HPLC-MS/MS and the application to cell pharmacokinetics.

    PubMed

    Lan, Xu; Mingdao, Lei; Huilin, Guo; Wei, Gan; Lvjiang, Hu; Yan, Zhou; Gang, Li

    2015-10-01

    A specific and reliable HPLC-MS/MS method was developed and validated for the simultaneous determination of 2',3'-dideoxyinosine (ddI) and the active metabolites, 2',3'-dideoxyadenosine-5'-triphosphate (ddA-TP) in human peripheral-blood mononuclear cell for the first time. The analytes were separated on a HILIC column (100mm×2.1mm, 1.7μm) and a triple-quadrupole mass spectrometry equipped with an electrospray ionization (ESI) source was used for detection. The cell homogenates sample was prepared by the solid phase extraction. The calibration curves were linear over a concentration range of 0.5-200.0ng/mL for ddI and 0.25-100.0ng/mL for ddA-TP. The intra-day and inter-day precision was less than 15% and the relative error (RE) were all within ±15%. The validated method was successfully applied to assess the disposition characteristics of ddI and support cell pharmacokinetics after the patients with AIDS were orally administrated with ddI and tenofovir disoproxyl fumarate (TDF).

  8. Development of a highly sensitive LC-MS/MS method for simultaneous determination of rupatadine and its two active metabolites in human plasma: Application to a clinical pharmacokinetic study.

    PubMed

    Sun, Chenglong; Li, Qian; Pan, Liping; Liu, Bing; Gu, Pan; Zhang, Junying; Ding, Li; Wu, Chungyong

    2015-01-01

    An easy LC-ESI-MS/MS method was developed and validated for simultaneous determination of rupatadine (RT) and its two active metabolites, namely desloratadine (DT) and 3-hydroxydesloratadine (3-OH-DT), in human plasma. The chromatographic separation was carried out on a C18 column with gradient elution by using methanol and 10mM ammonium acetate containing 0.1% (v/v) formic acid. The lower limit of quantification (LLOQ) was 0.05, 0.035 and 0.035 ng/mL for RT, DT and 3-OH-DT, respectively. The intra- and inter-day precision of analytes were within the range of 1.0-4.7% and 2.2-12.1%, respectively. The intra- and inter-day accuracy of analytes were within the range of -7.7% to 5.2% and -4.1% to 4.8%, respectively. The method was successfully applied to a pharmacokinetic study of RT and its two metabolite DT and 3-OH-DT in healthy volunteers following single (10, 20, 40 mg) and multiple (10 mg) oral doses of rupatadine fumarate tablets. PMID:25890211

  9. 77 FR 59890 - Foreign-Trade Zone 92-Gulfport, MS; Authorization of Production Activity; Gulf Ship, LLC...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-01

    ... notice in the Federal Register inviting public comment (77 FR 28569, 5-15-2012). The FTZ Board has... Ship, LLC (Shipbuilding); Gulfport, MS On May 10, 2012, the Mississippi Coast Foreign-Trade Zone, Inc... (FTZ) Board on behalf of Gulf Ship, LLC, within FTZ 92--Site 3, in Gulfport, Mississippi....

  10. Pentraxin-3 is upregulated in the central nervous system during MS and EAE, but does not modulate experimental neurological disease.

    PubMed

    Ummenthum, Kimberley; Peferoen, Laura A N; Finardi, Annamaria; Baker, David; Pryce, Gareth; Mantovani, Alberto; Bsibsi, Malika; Bottazzi, Barbara; Peferoen-Baert, Regina; van der Valk, Paul; Garlanda, Cecilia; Kipp, Markus; Furlan, Roberto; van Noort, Johannes M; Amor, Sandra

    2016-03-01

    Pentraxin-3 (PTX3), an acute-phase protein released during inflammation, aids phagocytic clearance of pathogens and apoptotic cells, and plays diverse immunoregulatory roles in tissue injury. In neuroinflammatory diseases, like MS, resident microglia could become activated by endogenous agonists for Toll like receptors (TLRs). Previously we showed a strong TLR2-mediated induction of PTX3 in cultured human microglia and macrophages by HspB5, which accumulates in glia during MS. Given the anti-inflammatory effects of HspB5, we examined the contribution of PTX3 to these effects in MS and its animal model EAE. Our data indicate that TLR engagement effectively induces PTX3 expression in human microglia, and that such expression is readily detectable in MS lesions. Enhanced PTX3 expression is prominently expressed in microglia in preactive MS lesions, and in microglia/macrophages engaged in myelin phagocytosis in actively demyelinating lesions. Yet, we did not detect PTX3 in cerebrospinal fluid of MS patients. PTX3 expression is also elevated in spinal cords during chronic relapsing EAE in Biozzi ABH mice, but the EAE severity and time course in PTX3-deficient mice did not differ from WT mice. Moreover, systemic PTX3 administration did not alter the disease onset or severity. Our findings reveal local functions of PTX3 during neuroinflammation in facilitating myelin phagocytosis, but do not point to a role for PTX3 in controlling the development of autoimmune neuroinflammation.

  11. Rapid screening and identification of active ingredients in licorice extract interacting with V3 loop region of HIV-1 gp120 using ACE and CE-MS.

    PubMed

    Li, Zhongjie; Zhao, Yiran; Lin, Weiwei; Ye, Min; Ling, Xiaomei

    2015-01-01

    The binding of envelope protein gp120 to glycosphingolipids is very important during the human immunodeficiency virus entering into the host cell. This step occurs in the V3 loop region in particularly. The conserved core sequence of V3 loop in gp120 was named R15K. Anti-HIV drug targeting to R15K would avoid the drug-resistance caused by HIV-1 genetic diversity. Here, for the first time, affinity capillary electrophoresis (ACE) and capillary electrophoresis-mass spectrometry (CE-MS) were used for establishing a simple, rapid and effective method of screening the licorice extract for biological activity (anti-HIV), which avoided the complicated isolation and purification process. R15K, 3'-sialyllactose (the positive control), and d-galactose (the negative control) were used for the development and validation of ACE method. After the interaction between licorice extract and R15K was confirmed by ACE, the relative active ingredients were isolated by SPE and their structures were determined by CE-ESI-MS online. In this research, two mixtures from licorice extract were found to be active. Furthermore, glycyrrhizin and licorice saponin G2 were verified as the main ingredients that significantly interacted with R15K via CE-MS and LC-MS. The results of quantitative assays showed that the active mixture contained glycyrrhizin of 74.23% and licorice saponin G2 of 9.52%. Calculated by Scatchard analysis method, glycyrrhizin/R15K complex had the highest binding constant (1.69 ± 0.08) × 10(7)L/mol among 27 compounds isolated from licorice extract. The anti-HIV activity of glycyrrhizin was further confirmed by bioactive experiment of cellular level. This strategy might provide a high throughput screening and identifying platform for seeking HIV-1 inhibitors in natural products.

  12. Validity and reproducibility of a laser fluorescence system for detecting the activity of white-spot lesions on free smooth surfaces in vivo.

    PubMed

    Pinelli, Camila; Campos Serra, Mônica; de Castro Monteiro Loffredo, Leonor

    2002-01-01

    The aim of the study was to determine the reproducibility and validity of DIAGNOdent in detecting active and arrested caries lesions on free smooth surfaces. Volunteers were selected from state schools of Piracicaba, São Paulo, Brazil. Overall, 220 lesions were clinically examined. Two specially trained ('calibrated') examiners performed both clinical and laser evaluations independently, and after a 1-week interval, the examinations were repeated. The intra-examiner agreement for the laser evaluation was substantial (kappa(ex1) = 0.79, kappa(ex2) = 0.71). There was almost perfect agreement between the two examiners for the clinical examination (kappa(ex1) = 0.95, kappa(ex2) = 0.85). The inter-examiner agreement showed substantial reproducibility (kappa = 0.77) for the laser examination and almost perfect agreement (kappa = 0.85) for the clinical evaluation. The validation criterion was the clinical examination of white spots, recorded as active or arrested. The sensitivity was 0.72 and the specificity was 0.73, which indicates that the DIAGNOdent was a good auxiliary method for detecting incipient caries lesions on free smooth surfaces. The utilization of both methods can improve the efficacy of caries diagnosis.

  13. Tocotrienol Attenuates Stress-Induced Gastric Lesions via Activation of Prostaglandin and Upregulation of COX-1 mRNA

    PubMed Central

    Kamisah, Yusof; Chua, Kien Hui; Qodriyah, Hj Mohd Saad

    2013-01-01

    The present study aims to distinguish the effect of tocotrienol on an important gastric protective factor, prostaglandin E2 (PGE2), in stress-induced gastric injury. Twenty-eight Wistar rats were divided into four groups of seven rats each. Two control groups were fed commercial rat diet, and two treatment groups were fed the same diet but with additional dose of omeprazole (20 mg/kg) or tocotrienol (60 mg/kg). After 28 days, rats from one control group and both treated groups were subjected to water-immersion restraint stress for 3.5 hours once. The rats were then sacrificed, their stomach isolated and gastric juice collected, lesions examined, and gastric PGE2 content and cyclooxygenase (COX) mRNA expression were determined. Both the regimes significantly attenuated the total lesion area in the stomach compared to the control. Gastric acidity, which was increased in stress, was significantly reduced in rats supplemented with omeprazole and tocotrienol. The PGE2 content was also significantly higher in the rats given tocotrienol supplementation compared to the control followed by an increase in COX-1 mRNA expression. We conclude that tocotrienol supplementation protected rat gastric mucosa against stress-induced lesions possibly by reducing gastric acidity and preserving gastric PGE2 by increasing COX-1 mRNA. PMID:23970937

  14. Inhibition of diethylnitrosamine-initiated alcohol-promoted hepatic inflammation and precancerous lesions by flavonoid luteolin is associated with increased sirtuin 1 activity in mice

    PubMed Central

    Rafacho, Bruna Paola Murino; Stice, Camilla Peach; Liu, Chun; Greenberg, Andrew S.; Ausman, Lynne M.

    2015-01-01

    Background Chronic and excessive alcohol consumption is an established risk for hepatic inflammation and carcinogenesis. Luteolin is one of the most common flavonoids present in plants and has potential beneficial effects against cancer. In this study, we examined the effect and potential mechanisms of luteolin supplementation in a carcinogen initiated alcohol-promoted pre-neoplastic liver lesion mouse model. Methods C57BL/6 mice were injected with diethylnitrosamine (DEN) [i.p. 25 mg/kg of body weight (BW)] at 14 days of age. At 8 weeks of age mice were group pair-fed with Lieber-DeCarli liquid control diet or alcoholic diet [ethanol (EtOH) diet, 27% total energy from ethanol] and supplemented with a dose of 30 mg luteolin/kg BW per day for 21 days. Results DEN-injected mice fed EtOH diet displayed a significant induction of pre-neoplastic lesions, a marker associated with presence of steatosis and inflammation. Dietary luteolin significantly reduced the severity and incidence of hepatic inflammatory foci and steatosis in DEN-injected mice fed EtOH diet, as well the presence of preneoplastic lesions. There was no difference on hepatic protein levels of sirtuin 1 (SIRT1) among all groups; however, luteolin supplementation significantly reversed alcohol-reduced SIRT1 activity assessed by the ratio of acetylated and total forkhead box protein O1 (FoXO1) and SIRT1 target proliferator-activated receptor gamma, coactivator 1 alpha (PGC1α). Conclusions Dietary intake of luteolin prevents alcohol promoted pre-neoplastic lesions, potentially mediated by SIRT1 signaling pathway. PMID:26005679

  15. detecting multiple sclerosis lesions with a fully bioinspired visual attention model

    NASA Astrophysics Data System (ADS)

    Villalon-Reina, Julio; Gutierrez-Carvajal, Ricardo; Thompson, Paul M.; Romero-Castro, Eduardo

    2013-11-01

    The detection, segmentation and quantification of multiple sclerosis (MS) lesions on magnetic resonance images (MRI) has been a very active field for the last two decades because of the urge to correlate these measures with the effectiveness of pharmacological treatment. A myriad of methods has been developed and most of these are non specific for the type of lesions and segment the lesions in their acute and chronic phases together. On the other hand, radiologists are able to distinguish between several stages of the disease on different types of MRI images. The main motivation of the work presented here is to computationally emulate the visual perception of the radiologist by using modeling principles of the neuronal centers along the visual system. By using this approach we are able to detect the lesions in the majority of the images in our population sample. This type of approach also allows us to study and improve the analysis of brain networks by introducing a priori information.

  16. Cognitive performances and locomotor activity following dentate granule cell damage in rats: role of lesion extent and type of memory tested.

    PubMed

    Jeltsch, H; Bertrand, F; Lazarus, C; Cassel, J C

    2001-07-01

    Intradentate injection of colchicine is one of the techniques used to destroy granule cells. This study compared the behavioral effects of various amounts of colchicine (1.0, 3.0, and 6.0 microg; Col 1, Col 3, and Col 6, respectively) injected into the dentate gyrus of adult Long-Evans male rats. Starting 10 days after lesion surgery, behavioral testing assessed home-cage and open-field locomotion, alternation in a T-maze, water-maze, and radial-maze learning according to protocols placing emphasis on reference, and working memory. All of these tasks are sensitive to hippocampal disruption. Histological verifications showed that the extent of the lesions depends on the dose of colchicine (index of dentate gyrus shrinkage: -33% in Col 1, -54% in Col 3, and -67% in Col 6 rats). Colchicine dose-dependently increased nocturnal home cage activity (an effect found 10 days but not 5 months after surgery), but had no significant effect on open-field locomotion or T-maze alternation. A dose-dependent reference memory impairment was found during the acquisition of spatial navigation in the water maze; Col 3 and Col 6 rats were more impaired than Col 1 rats. During the probe trial (platform removed), control rats spent a longer distance swimming over the platform area than all rats with colchicine lesions. In the working memory version of the test, all rats with colchicine lesions showed significant deficits. The deficits were larger in Col 3 and Col 6 rats compared to Col 1 rats. The lesions had no effect on swimming speed. In the radial-maze test, there was also a dose-dependent working memory impairment. However, reference memory was disrupted in a manner that did not differ among the three groups of lesioned rats. Our data are in line with the view that the dentate gyrus plays an important role in the acquisition of new information and is an integral neural substrate for spatial reference and spatial working memory. They also suggest that damage to granule cells might

  17. Rapid Identification and Assignation of the Active Ingredients in Fufang Banbianlian Injection Using HPLC-DAD-ESI-IT-TOF-MS.

    PubMed

    Li, Sensen; Lin, Zongtao; Jiang, Haixiu; Tong, Lingkun; Wang, Hong; Chen, Shizhong

    2016-08-01

    Fufang Banbianlian Injection (FBI) is a well-known traditional Chinese medicine formula composed of three herbal medicines. However, the systematic investigation on its chemical components has not been reported yet. In this study, a high-performance liquid chromatography combined with diode-array detector, and coupled to an electrospray ionization with ion-trap time-of-flight mass spectrometry (HPLC-DAD-ESI-IT-TOF-MS) method, was established for the identification of chemical profile in FBI. Sixty-six major constituents (14 phenolic acids, 14 iridoids, 20 flavonoids, 2 benzylideneacetone compounds, 3 phenylethanoid glycosides, 1 coumarin, 1 lignan, 3 nucleosides, 1 amino acids, 1 monosaccharides, 2 oligosaccharides, 3 alduronic acids and citric acid) were identified or tentatively characterized by comparing their retention times and MS spectra with those of standards or literature data. Finally, all constituents were further assigned in the individual herbs (InHs), although some of them were from multiple InHs. As a result, 11 compounds were from Lobelia chinensis Lour, 33 compounds were from Scutellaria barbata D. Don and 38 compounds were from Hedyotis diffusa Willd. In conclusion, the developed HPLC-DAD-ESI-IT-TOF-MS method is a rapid and efficient technique for analysis of FBI sample, and could be a valuable method for the further study on the quality control of the FBI.

  18. Rapid Identification and Assignation of the Active Ingredients in Fufang Banbianlian Injection Using HPLC-DAD-ESI-IT-TOF-MS.

    PubMed

    Li, Sensen; Lin, Zongtao; Jiang, Haixiu; Tong, Lingkun; Wang, Hong; Chen, Shizhong

    2016-08-01

    Fufang Banbianlian Injection (FBI) is a well-known traditional Chinese medicine formula composed of three herbal medicines. However, the systematic investigation on its chemical components has not been reported yet. In this study, a high-performance liquid chromatography combined with diode-array detector, and coupled to an electrospray ionization with ion-trap time-of-flight mass spectrometry (HPLC-DAD-ESI-IT-TOF-MS) method, was established for the identification of chemical profile in FBI. Sixty-six major constituents (14 phenolic acids, 14 iridoids, 20 flavonoids, 2 benzylideneacetone compounds, 3 phenylethanoid glycosides, 1 coumarin, 1 lignan, 3 nucleosides, 1 amino acids, 1 monosaccharides, 2 oligosaccharides, 3 alduronic acids and citric acid) were identified or tentatively characterized by comparing their retention times and MS spectra with those of standards or literature data. Finally, all constituents were further assigned in the individual herbs (InHs), although some of them were from multiple InHs. As a result, 11 compounds were from Lobelia chinensis Lour, 33 compounds were from Scutellaria barbata D. Don and 38 compounds were from Hedyotis diffusa Willd. In conclusion, the developed HPLC-DAD-ESI-IT-TOF-MS method is a rapid and efficient technique for analysis of FBI sample, and could be a valuable method for the further study on the quality control of the FBI. PMID:27107094

  19. Investigation of ex vivo stability of fesoterodine in human plasma and its simultaneous determination together with its active metabolite 5-HMT by LC-ESI-MS/MS: Application to a bioequivalence study.

    PubMed

    Parekh, Jignesh M; Sanyal, Mallika; Yadav, Manish; Shrivastav, Pranav S

    2013-01-15

    Fesoterodine is a non-selective muscarinic-receptor antagonist, used in the treatment of overactive bladder syndrome. A highly sensitive, selective and rapid method has been developed for the simultaneous determination of fesoterodine and its active metabolite, 5-hydroxymethyl tolterodine (5-HMT) in human plasma by liquid chromatography-tandem mass spectrometry (LC-ESI-MS/MS). Due to rapid conversion of parent drug to 5-HMT, ex vivo stability of fesoterodine in human plasma was extensively studied to optimize the extraction protocol. The analytes and their deuterated analogs were quantitatively extracted from 100μL human plasma by liquid-liquid extraction in methyl tert-butyl ether: n-hexane. The chromatographic separation of analytes was achieved on a Kromasil C18 (100mm×4.6mm, 5μm) column under isocratic conditions. The method was validated over a dynamic concentration range of 0.01-10ng/mL for both the analytes. Ion-suppression effects were investigated by post-column infusion of analytes. The precision (% CV) values for the calculated slopes of calibration curves, which would reflect the relative matrix effect, were less than 1.5% for both the analytes. The intra-batch and inter-batch precision (% CV) across quality control levels varied from 1.82 to 3.73% and the mean extraction recovery was >96% for both the analytes. The method was successfully applied to a bioequivalence study of 8mg fesoterodine tablet formulation (test and reference) in 12 healthy Indian subjects under fasted and fed condition. The assay reproducibility estimated by reanalysis of incurred samples showed a change of ±12.0%. PMID:23266359

  20. Simultaneous quantification of fosinopril and its active metabolite fosinoprilat in rat plasma by UFLC-MS/MS: Application of formic acid in the stabilization of an ester-containing drug.

    PubMed

    Xue, Kewen; Li, Gao; Sun, Xiao; Hu, Yang; Hu, Lei; Huang, Jiangeng; Si, Luqin

    2015-05-15

    Fosinopril is an angiotensin-converting enzyme inhibitor containing a phosphate ester group which undergoes esterase hydrolysis to its active metabolite, fosinoprilat. EDTA was utilized as an anticoagulant to inhibit the hydrolysis of fosinopril in whole blood during blood collection and processing. To prevent the ex vivo conversion to fosinoprilat, formic acid was added to rat plasma to effectively stabilize fosinopril. A sensitive, rapid and robust ultra-fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) method was developed and validated for simultaneous determination of fosinopril and fosinoprilat in rat plasma. Protein precipitation was employed for plasma sample clean-up. Chromatographic separation was achieved on a Welch Ultimate XB-C18 column using gradient elution with a total run time of 5min. Analytes and their stable isotope labeled internal standards were detected by positive ion electrospray tandem mass spectrometric assay. The assay involves quantitation of both analytes in small-volume (50μL) plasma, with the lower limit of quantification of 0.1 and 1ng/mL for fosinopril and fosinoprilat, respectively. The method was fully validated in linear calibration ranges of 0.1-150ng/mL for fosinopril and 1-1500ng/mL for fosinoprilat with acceptable accuracy and precision. Assay recoveries were high (>95% for fosinopril and >91% for fosinoprilat) and matrix effect was negligible. Both analytes were found to be stable in stabilized rat plasma for 6h at room temperature, 30 days at -80°C, and following three freeze-thaw cycles and were also stable in processed samples for 36h at 4°C. The validated method was successfully applied to sample analyses for pharmacokinetic study of fosinopril and can be extended to the measurement of fosinopril in other biological samples. PMID:25875586

  1. Simultaneous determination of parecoxib sodium and its active metabolite valdecoxib in rat plasma by UPLC-MS/MS and its application to a pharmacokinetic study after intravenous and intramuscular administration.

    PubMed

    Liu, Meina; Yu, Qiuyang; Li, Ping; Zhu, Meng; Fang, Mingming; Sun, Bingjun; Sun, Mengchi; Sun, Yinghua; Zhang, Peng; He, Zhonggui; Sun, Jin; Wang, Yongjun; Liu, Xiaohong

    2016-06-01

    In this study, we developed and validated a new, rapid, specific and sensitive ultra-performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method to simultaneously determine parecoxib sodium (PX) and its active metabolite, valdecoxib (VX), in rat plasma. Plasma samples were prepared by plasma protein precipitation combined with a liquid-liquid extraction method. The separation was carried out on a Kinetex C18 column (2.1mm×50mm, 2.6μm) with a gradient elution using methanol (A) and a 2mM ammonium acetate aqueous solution (B). The analysis was performed in less than 3min with a flow rate of 0.2mL/min. Ketoprofen was used as an internal standard (IS). Mass spectrometric detection was conducted with a triple quadrupole detector equipped with electrospray ionization in the negative ion mode (ESI(-)) using multiple reaction monitoring (MRM). The calibration curves were linear over the concentration ranges of 5-4000ng/mL for PX and 5-2000ng/mL for VX with all correlation coefficients greater than 0.998. The intra- and inter-day relative standard deviations (RSD) for both analytes were within 15% and the accuracy was within 85-115% at all quality control levels. The mean extraction recoveries for all analytes obtained from three concentrations of QC plasma samples were more than 89.0% efficient. Selectivity, matrix effect, dilution integrity and stability were also validated. The method was successfully used to investigate the pharmacokinetics of PX and VX in rat plasma after intravenous and intramuscular administration of PX. PMID:27107851

  2. Rapid discovery and identification of anti-inflammatory constituents from traditional Chinese medicine formula by activity index, LC-MS, and NMR

    PubMed Central

    Wang, Shufang; Wang, Haiqiang; Liu, Yining; Wang, Yi; Fan, Xiaohui; Cheng, Yiyu

    2016-01-01

    The traditional activity-guided approach has the shortcoming of low accuracy and efficiency in discovering active compounds from TCM. In this work, an approach was developed by integrating activity index (AI), liquid chromatography – mass spectrometry (LC-MS), and nuclear magnetic resonance (NMR) to rapidly predict and identify the potential active constituents from TCM. This approach was used to discover and identify the anti-inflammatory constituents from a TCM formula, Gui-Zhi-Jia-Shao-Yao-Tang (GZJSYT). The AI results indicated that, among the 903 constituents detected in GZJSYT by LC-MS, 61 constituents with higher AI values were very likely to have anti-inflammatory activities. And eight potential active constituents of them were isolated and validated to have significant inhibitory effects against NO production on LPS-induced RAW 264.7 cell model. Among them, glycyrrhisoflavone (836), glisoflavanone (893) and isoangustone A (902) were reported to have anti-inflammatory effects for the first time. The proposed approach could be generally applicable for rapid and high efficient discovery of anti-inflammatory constituents from other TCM formulae or natural products. PMID:27499135

  3. Rapid discovery and identification of anti-inflammatory constituents from traditional Chinese medicine formula by activity index, LC-MS, and NMR.

    PubMed

    Wang, Shufang; Wang, Haiqiang; Liu, Yining; Wang, Yi; Fan, Xiaohui; Cheng, Yiyu

    2016-01-01

    The traditional activity-guided approach has the shortcoming of low accuracy and efficiency in discovering active compounds from TCM. In this work, an approach was developed by integrating activity index (AI), liquid chromatography - mass spectrometry (LC-MS), and nuclear magnetic resonance (NMR) to rapidly predict and identify the potential active constituents from TCM. This approach was used to discover and identify the anti-inflammatory constituents from a TCM formula, Gui-Zhi-Jia-Shao-Yao-Tang (GZJSYT). The AI results indicated that, among the 903 constituents detected in GZJSYT by LC-MS, 61 constituents with higher AI values were very likely to have anti-inflammatory activities. And eight potential active constituents of them were isolated and validated to have significant inhibitory effects against NO production on LPS-induced RAW 264.7 cell model. Among them, glycyrrhisoflavone (836), glisoflavanone (893) and isoangustone A (902) were reported to have anti-inflammatory effects for the first time. The proposed approach could be generally applicable for rapid and high efficient discovery of anti-inflammatory constituents from other TCM formulae or natural products. PMID:27499135

  4. Accuracy of 99mTc (V)-Dimercaptosuccinic Acid Scintigraphy and Fecal Calprotectin Compared with Colonoscopy in Localizing Active Lesions in Inflammatory Bowel Disease

    PubMed Central

    Basirat, Vahid; Azizi, Zahra; Javid Anbardan, Sanam; Taghizadeh Asl, Mina; Farbod, Yasaman; Teimouri, Azam; Ebrahimi Daryani, Nasser

    2016-01-01

    INTRODUCTION Due to limitation of colonoscopy in assessing the entire bowel and patients’ intolerance in inflammatory bowel disease (IBD), in the current study, we aimed to prospectively compare the accuracy of 99mTc(V)-dimercaptosuccinic acid (DMSA) and fecal calprotectin with ileocolonoscopy as new methods for localizing inflammations. METHODS Current prospective study conducted between 2012 and 2014 on 30 patients with IBD attending Gastroenterology Clinic of Tehran University of Medical Sciences. Fecal calprotectin and disease activity were measured for all participants and all of them underwent 99mTc (V)-DMSA scintigraphy and colonoscopy. The accuracy of 99mTc (V)-DMSA scintigraphy and calprotectin in localizing bowel lesions were calculated. RESULTS A total of 22 patients with ulcerative colitis (UC) and 8 patients with Crohn’s disease (CD) were evaluated in our study. Sensitivity, positive likelihood ratio (PLR), and positive predictive value (PPV) of scintigraphy and calprotectin over colonoscopy in localization of UC lesions were 86.36%, 0.86%, 100.00% and 90.91%, 0.91, and 100.00%, respectively. Meanwhile, it showed 66.67% sensitivity and 81.25% specificity with PLR=3.56, negative likelihood ratio (NLR)=0.41, PPV=84.21%, and negative predictive value (NPV)= 61.90% in localizing lesions in patients with CD. The calprotectin level had sensitivity, PLR, and PPV of 90.00%, 0.90, and 100.00% in detecting active disease over colonoscopy, respectively. CONCLUSION The 99mTc (V)-DMSA scintigraphy would be an accurate method for detecting active inflammation in follow-up of patients with IBD and assessing response to treatment as a non-invasive and complementary method beside colonoscopy for more accurate diagnosis of CD or UC. PMID:27698971

  5. Molecular pathobiology of human cervical high-grade lesions: paracrine STAT3 activation in tumor-instructed myeloid cells drives local MMP-9 expression.

    PubMed

    Schröer, Nadine; Pahne, Jennifer; Walch, Barbara; Wickenhauser, Claudia; Smola, Sigrun

    2011-01-01

    In many tumors, the switch from precancerous lesions to malignancy critically relies on expression of the matrix-metalloprotease MMP-9, which is predominantly provided by infiltrating inflammatory cells. Our study defines a novel molecular cascade, how human neoplastic cells instruct tumor-associated myeloid cells to produce MMP-9. In biopsies of human papillomavirus-associated precancerous cervical intraepithelial neoplasia (CIN III lesions), we show broad activation of the transcription factor STAT3 and coexpression of MMP-9 in perivascular inflammatory cells. For the first time, we establish a causative link between tumor-mediated paracrine STAT3 activation and MMP-9 production by human tumor-instructed monocytes, whereas NF-κB activation is dispensable for this response. Our data provide evidence that STAT3 does not directly induce MMP-9 but first leads to a strong production of the monocyte chemoattractant protein-1 (CCL2) in the nanogram range. In a second phase, autocrine stimulation of the CCR2 receptor in the tumor-instructed monocytes amplifies MMP-9 expression via intracellular Ca(2+) signaling. These findings elucidate a critical mechanism in the molecular pathobiology of cervical carcinogenesis at the switch to malignancy. Particularly in tumors, which are associated with infectious agents, STAT3-driven inflammation may be pivotal to promote carcinogenesis, while at the same time limit NF-κB-dependent immune responses and thus rejection of the infected preneoplastic cells. The molecular cascade defined in this study provides the basis for a rational design of future adjuvant therapies of cervical precancerous lesions.

  6. Accuracy of 99mTc (V)-Dimercaptosuccinic Acid Scintigraphy and Fecal Calprotectin Compared with Colonoscopy in Localizing Active Lesions in Inflammatory Bowel Disease

    PubMed Central

    Basirat, Vahid; Azizi, Zahra; Javid Anbardan, Sanam; Taghizadeh Asl, Mina; Farbod, Yasaman; Teimouri, Azam; Ebrahimi Daryani, Nasser

    2016-01-01

    INTRODUCTION Due to limitation of colonoscopy in assessing the entire bowel and patients’ intolerance in inflammatory bowel disease (IBD), in the current study, we aimed to prospectively compare the accuracy of 99mTc(V)-dimercaptosuccinic acid (DMSA) and fecal calprotectin with ileocolonoscopy as new methods for localizing inflammations. METHODS Current prospective study conducted between 2012 and 2014 on 30 patients with IBD attending Gastroenterology Clinic of Tehran University of Medical Sciences. Fecal calprotectin and disease activity were measured for all participants and all of them underwent 99mTc (V)-DMSA scintigraphy and colonoscopy. The accuracy of 99mTc (V)-DMSA scintigraphy and calprotectin in localizing bowel lesions were calculated. RESULTS A total of 22 patients with ulcerative colitis (UC) and 8 patients with Crohn’s disease (CD) were evaluated in our study. Sensitivity, positive likelihood ratio (PLR), and positive predictive value (PPV) of scintigraphy and calprotectin over colonoscopy in localization of UC lesions were 86.36%, 0.86%, 100.00% and 90.91%, 0.91, and 100.00%, respectively. Meanwhile, it showed 66.67% sensitivity and 81.25% specificity with PLR=3.56, negative likelihood ratio (NLR)=0.41, PPV=84.21%, and negative predictive value (NPV)= 61.90% in localizing lesions in patients with CD. The calprotectin level had sensitivity, PLR, and PPV of 90.00%, 0.90, and 100.00% in detecting active disease over colonoscopy, respectively. CONCLUSION The 99mTc (V)-DMSA scintigraphy would be an accurate method for detecting active inflammation in follow-up of patients with IBD and assessing response to treatment as a non-invasive and complementary method beside colonoscopy for more accurate diagnosis of CD or UC.

  7. HepG2 cells biospecific extraction and HPLC-ESI-MS analysis for screening potential antiatherosclerotic active components in Bupeuri radix.

    PubMed

    Liu, Shuqiang; Tan, Zhibin; Li, Pingting; Gao, Xiaoling; Zeng, Yuaner; Wang, Shuling

    2016-03-20

    HepG2 cells biospecific extraction method and high performance liquid chromatography-electrospray ionization-mass spectrometry (HPLC-ESI-MS) analysis was proposed for screening of potential antiatherosclerotic active components in Bupeuri radix, a well-known Traditional Chinese Medicine (TCM). The hypothesis suggested that when cells are incubated together with the extracts of TCM, the potential bioactive components in the TCM should selectively combine with the receptor or channel of HepG2 cells, then the eluate which contained biospecific component binding to HepG2 cells was identified using HPLC-ESI-MS analysis. The potential bioactive components of Bupeuri radix were investigated using the proposed approach. Five compounds in the saikosaponins of Bupeuri radix were detected as these components selectively combined with HepG2 cells, among these compounds, two potentially bioactive compounds namely saikosaponin b1 and saikosaponin b2 (SSb2) were identified by comparing with the chromatography of the standard sample and analysis of the structural clearance characterization of MS. Then SSb2 was used to assess the uptake of DiI-high density lipoprotein (HDL) in HepG2 cells for antiatherosclerotic activity. The results have showed that SSb2, with indicated concentrations (5, 15, 25, and 40 μM) could remarkably uptake dioctadecylindocarbocyanine labeled- (DiI) -HDL in HepG2 cells (Vs control group, *P<0.01). In conclusion, the application of HepG2 biospecific extraction coupled with HPLC-ESI-MS analysis is a rapid, convenient, and reliable method for screening potential bioactive components in TCM and SSb2 may be a valuable novel drug agent for the treatment of atherosclerosis.

  8. Validation of the Endopep-MS method for qualitative detection of active botulinum neurotoxins in human and chicken serum.

    PubMed

    Björnstad, Kristian; Tevell Åberg, Annica; Kalb, Suzanne R; Wang, Dongxia; Barr, John R; Bondesson, Ulf; Hedeland, Mikael

    2014-11-01

    Botulinum neurotoxins (BoNTs) are highly toxic proteases produced by anaerobic bacteria. Traditionally, a mouse bioassay (MBA) has been used for detection of BoNTs, but for a long time, laboratories have worked with alternative methods for their detection. One of the most promising in vitro methods is a combination of an enzymatic and mass spectrometric assay called Endopep-MS. However, no comprehensive validation of the method has been presented. The main purpose of this work was to perform a validation for the qualitative analysis of BoNT-A, B, C, C/D, D, D/C, and F in serum. The limit of detection (LOD), selectivity, precision, stability in matrix and solution, and correlation with the MBA were evaluated. The LOD was equal to or even better than that of the MBA for BoNT-A, B, D/C, E, and F. Furthermore, Endopep-MS was for the first time successfully used to differentiate between BoNT-C and D and their mosaics C/D and D/C by different combinations of antibodies and target peptides. In addition, sequential antibody capture was presented as a new way to multiplex the method when only a small sample volume is available. In the comparison with the MBA, all the samples analyzed were positive for BoNT-C/D with both methods. These results indicate that the Endopep-MS method is a valid alternative to the MBA as the gold standard for BoNT detection based on its sensitivity, selectivity, and speed and that it does not require experimental animals.

  9. Effect of glatiramer acetate three-times weekly on the evolution of new, active multiple sclerosis lesions into T1-hypointense "black holes": a post hoc magnetic resonance imaging analysis.

    PubMed

    Zivadinov, Robert; Dwyer, Michael; Barkay, Hadas; Steinerman, Joshua R; Knappertz, Volker; Khan, Omar

    2015-03-01

    Conversion of active lesions to black holes has been associated with disability progression in subjects with relapsing-remitting multiple sclerosis (RRMS) and represents a complementary approach to evaluating clinical efficacy. The objective of this study was to assess the conversion of new active magnetic resonance imaging (MRI) lesions, identified 6 months after initiating treatment with glatiramer acetate 40 mg/mL three-times weekly (GA40) or placebo, to T1-hypointense black holes in subjects with RRMS. Subjects received GA40 (n = 943) or placebo (n = 461) for 12 months. MRI was obtained at baseline and Months 6 and 12. New lesions were defined as either gadolinium-enhancing T1 or new T2 lesions at Month 6 that were not present at baseline. The adjusted mean numbers of new active lesions at Month 6 converting to black holes at Month 12 were analyzed using a negative binomial model; adjusted proportions of new active lesions at Month 6 converting to black holes at Month 12 were analyzed using a logistic regression model. Of 1,292 subjects with complete MRI data, 433 (50.3 %) GA-treated and 247 (57.2 %) placebo-treated subjects developed new lesions at Month 6. Compared with placebo, GA40 significantly reduced the mean number (0.31 versus 0.45; P = .0258) and proportion (15.8 versus 19.6 %; P = .006) of new lesions converting to black holes. GA significantly reduced conversion of new active lesions to black holes, highlighting the ability of GA40 to prevent tissue damage in RRMS. PMID:25542295

  10. Effect of glatiramer acetate three-times weekly on the evolution of new, active multiple sclerosis lesions into T1-hypointense "black holes": a post hoc magnetic resonance imaging analysis.

    PubMed

    Zivadinov, Robert; Dwyer, Michael; Barkay, Hadas; Steinerman, Joshua R; Knappertz, Volker; Khan, Omar

    2015-03-01

    Conversion of active lesions to black holes has been associated with disability progression in subjects with relapsing-remitting multiple sclerosis (RRMS) and represents a complementary approach to evaluating clinical efficacy. The objective of this study was to assess the conversion of new active magnetic resonance imaging (MRI) lesions, identified 6 months after initiating treatment with glatiramer acetate 40 mg/mL three-times weekly (GA40) or placebo, to T1-hypointense black holes in subjects with RRMS. Subjects received GA40 (n = 943) or placebo (n = 461) for 12 months. MRI was obtained at baseline and Months 6 and 12. New lesions were defined as either gadolinium-enhancing T1 or new T2 lesions at Month 6 that were not present at baseline. The adjusted mean numbers of new active lesions at Month 6 converting to black holes at Month 12 were analyzed using a negative binomial model; adjusted proportions of new active lesions at Month 6 converting to black holes at Month 12 were analyzed using a logistic regression model. Of 1,292 subjects with complete MRI data, 433 (50.3 %) GA-treated and 247 (57.2 %) placebo-treated subjects developed new lesions at Month 6. Compared with placebo, GA40 significantly reduced the mean number (0.31 versus 0.45; P = .0258) and proportion (15.8 versus 19.6 %; P = .006) of new lesions converting to black holes. GA significantly reduced conversion of new active lesions to black holes, highlighting the ability of GA40 to prevent tissue damage in RRMS.

  11. Integrated LC-MS/MS system for plant metabolomics

    PubMed Central

    Sawada, Yuji; Hirai, Masami Yokota

    2013-01-01

    Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is highly sensitive, selective, and enables extensive detection of metabolites within a sample. The result allows us to characterize comprehensive metabolite accumulation patterns without dependence on authentic standard compounds and isolation of the individual metabolites. A reference database search is essential for the structural assignment process of un-targeted MS and MS/MS data. Moreover, the characterization of unknown metabolites is challenging, since these cannot be assigned a candidate structure by using a reference database. In this case study, integrated LC-MS/MS based plant metabolomics allows us to detect several hundred metabolites in a sample; and integrated omics analyses, e.g., large-scale reverse genetics, linkage mapping, and association mapping, provides a powerful tool for candidate structure selection or rejection. We also examine emerging technology and applications for LC-MS/MS-based un-targeted plant metabolomics. These activities promote the characterization of massive extended detectable metabolites. PMID:24688692

  12. Superior MRI outcomes with alemtuzumab compared with subcutaneous interferon β-1a in MS

    PubMed Central

    Fisher, Elizabeth; Brinar, Vesna V.; Cohen, Jeffrey A.; Coles, Alasdair J.; Giovannoni, Gavin; Hartung, Hans-Peter; Havrdova, Eva; Selmaj, Krzysztof W.; Stojanovic, Miroslav; Weiner, Howard L.; Lake, Stephen L.; Margolin, David H.; Thomas, David R.; Panzara, Michael A.; Compston, D. Alastair S.

    2016-01-01

    Objective: To describe detailed MRI results from 2 head-to-head phase III trials, Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis Study I (CARE-MS I; NCT00530348) and Study II (CARE-MS II; NCT00548405), of alemtuzumab vs subcutaneous interferon β-1a (SC IFN-β-1a) in patients with active relapsing-remitting multiple sclerosis (RRMS). Methods: The impact of alemtuzumab 12 mg vs SC IFN-β-1a 44 μg on MRI measures was evaluated in patients with RRMS who were treatment-naive (CARE-MS I) or who had an inadequate response, defined as at least one relapse, to prior therapy (CARE-MS II). Results: Both treatments prevented T2-hyperintense lesion volume increases from baseline. Alemtuzumab was more effective than SC IFN-β-1a on most lesion-based endpoints in both studies (p < 0.05), including decreased risk of new/enlarging T2 lesions over 2 years and gadolinium-enhancing lesions at year 2. Reduced risk of new T1 lesions (p < 0.0001) and gadolinium-enhancing lesion conversion to T1-hypointense black holes (p = 0.0078) were observed with alemtuzumab vs SC IFN-β-1a in CARE-MS II. Alemtuzumab slowed brain volume loss over 2 years in CARE-MS I (p < 0.0001) and II (p = 0.012) vs SC IFN-β-1a. Conclusions: Alemtuzumab demonstrated greater efficacy than SC IFN-β-1a on MRI endpoints in active RRMS. The superiority of alemtuzumab was more prominent during the second year of both studies. These findings complement the superior clinical efficacy of alemtuzumab over SC IFN-β-1a in RRMS. ClinicalTrials.gov identifier: NCT00530348 and NCT00548405. Classification of evidence: The results reported here provide Class I evidence that, for patients with active RRMS, alemtuzumab is superior to SC IFN-β-1a on multiple MRI endpoints. PMID:27590291

  13. Evidence for preferential repair of 3-carbethoxypsoralen plus UVA induced DNA lesions in the active MAT alpha locus in Saccharomyces cerevisiae using the UvrABC assay.

    PubMed

    Méniel, V; Brouwer, J; Averbeck, D

    1993-09-01

    The occurrence of preferential repair in Saccharomyces cerevisiae of the active MAT alpha locus compared with the inactive HML alpha locus was confirmed after 254 nm UV irradiation. Experiments carried out using the UvrABC excinuclease assay with the monofunctional furocoumarin 3-carbethoxypsoralen (3-CPs) plus UVA radiation which induce mainly monoadducts in DNA demonstrated preferential repair of the active MAT alpha locus compared with the inactive HML alpha locus in a SIR+ strain. However, as after 254 nm UV irradiation, no difference in the rate of removal of 3-CPs plus UVA induced lesions was observed between the two loci in the sir-3 mutant in which both loci are active. Thus, it appears that 3-CPs plus UVA induced monoadducts as well as pyrimidine dimers are subject to preferential repair.

  14. In Vitro Pharmacological Activities and GC-MS Analysis of Different Solvent Extracts of Lantana camara Leaves Collected from Tropical Region of Malaysia

    PubMed Central

    Swamy, Mallappa Kumara; Akhtar, Mohd. Sayeed

    2015-01-01

    We investigated the effect of different solvents (ethyl acetate, methanol, acetone, and chloroform) on the extraction of phytoconstituents from Lantana camara leaves and their antioxidant and antibacterial activities. Further, GC-MS analysis was carried out to identify the bioactive chemical constituents occurring in the active extract. The results revealed the presence of various phytocompounds in the extracts. The methanol solvent recovered higher extractable compounds (14.4% of yield) and contained the highest phenolic (92.8 mg GAE/g) and flavonoid (26.5 mg RE/g) content. DPPH radical scavenging assay showed the IC50 value of 165, 200, 245, and 440 μg/mL for methanol, ethyl acetate, acetone, and chloroform extracts, respectively. The hydroxyl scavenging activity test showed the IC50 value of 110, 240, 300, and 510 μg/mL for methanol, ethyl acetate, acetone, and chloroform extracts, respectively. Gram negative bacterial pathogens (E. coli and K. pneumoniae) were more susceptible to all extracts compared to Gram positive bacteria (M. luteus, B. subtilis, and S. aureus). Methanol extract had the highest inhibition activity against all the tested microbes. Moreover, methanolic extract of L. camara contained 32 bioactive components as revealed by GC-MS study. The identified major compounds included hexadecanoic acid (5.197%), phytol (4.528%), caryophyllene oxide (4.605%), and 9,12,15-octadecatrienoic acid, methyl ester, (Z,Z,Z)- (3.751%). PMID:26783409

  15. Antioxidant activity of leaf extracts from different Hibiscus sabdariffa accessions and simultaneous determination five major antioxidant compounds by LC-Q-TOF-MS.

    PubMed

    Wang, Jin; Cao, Xianshuang; Jiang, Hao; Qi, Yadong; Chin, Kit L; Yue, Yongde

    2014-12-17

    Hibiscus sabdariffa has gained attention for its antioxidant activity. There are many accessions of H. sabdariffa in the world. However, information on the quantification of antioxidant compounds in different accessions is rather limited. In this paper, a liquid chromatography/quadrupole-time-of-flight mass spectrometry (LC-Q-TOF-MS) method for simultaneous determination of five antioxidant compounds (neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, rutin, and isoquercitrin) in H. sabdariffa leaves was developed. The method was validated for linearity, sensitivity, precision, repeatability and accuracy. The validated method has been successfully applied for determination of the five analytes in eight accessions of H. sabdariffa. The eight accessions of H. sabdariffa were evaluated for their antioxidant activities by DPPH free radical scavenging assay. The investigated accessions of H. sabdariffa were rich in rutin and exhibited strong antioxidant activity. The two accessions showing the highest antioxidant activities were from Cuba (No. 2) and Taiwan (No. 5). The results indicated that H. sabdariffa leaves could be considered as a potential antioxidant source for the food industry. The developed LC-Q-TOF-MS method is helpful for quality control of H. sabdariffa.

  16. Development and validation of a sensitive GC-MS method for the determination of trace levels of an alkylating reagent in a beta-lactam active pharmaceutical ingredient.

    PubMed

    Li, Hanlin; Sluggett, Gregory W

    2005-09-15

    A direct injection gas chromatographic method utilizing selected-ion monitoring (SIM) mode mass selective detection was developed and validated for the trace analysis of an impurity, carbonic acid chloromethyl tetrahydro-pyran-4-yl ester (CCMTHP), present in a beta-lactam active pharmaceutical ingredient (API). A variety of analytical techniques including LC-MS, GC-FID, GC-ECD and GC-MS were evaluated during the method development. GC-MS with SIM at m/z=49 demonstrated the best detection sensitivity. A 10 ppm (5 pg on column) limit of quantitation (LOQ) was attained and the linearity of the method was demonstrated in the range of 10-1000 ppm. Accurate and precise quantitation of the impurity in drug substance was achieved with external standardization. A 10:1 split injection was applied to limit the amount of non-volatile API loading onto the column. The effects of injection and detection parameters such as split ratio, liner type, injection temperature and number of mass ions monitored were studied. Full validation proved the accuracy, precision and specificity of the method, which was successfully employed to analyze many pilot lots of the API. PMID:15951149

  17. Free radical scavenging activity and characterization of sesquiterpenoids in four species of Curcuma using a TLC bioautography assay and GC-MS analysis.

    PubMed

    Zhao, Jing; Zhang, Jiang-Sheng; Yang, Bin; Lv, Guang-Ping; Li, Shao-Ping

    2010-10-27

    The sesquiterpenoids are one of major groups of antioxidants in Curcuma besides curcuminoids. However, the real substances contributing to the antioxidant activity are still unknown. In this paper, the antioxidant activity of sesquiterpenoids in four species and two essential oils from Curcuma genus was determined and compared based on TLC separation and DPPH bioautography assay. Their antioxidant capacities were quantitatively evaluated using densitometry with detection at 530 nm (λ(reference )= 800 nm) using vitamin C as reference. The results showed that Curcuma longa rhizomes had the highest antioxidant capacity while C. phaeocaulis presented the lowest one among the four species of Curcuma. Moreover, essential oil of C. wenyujin showed higher antioxidant potential than that of C. longa. The main TLC bands with antioxidant activity of the four species of Curcuma were collected and characterized using GC-MS, and thus curzerene, furanodiene, α-turmerone, β-turmerone and β-sesquiphellandrene were determined as major sesquiterpenoids with antioxidant activity in Curcuma.

  18. Fluorescence spectra and biological activity of aerosolized bacillus spores and MS2 bacteriophage exposed to ozone at different relative humidities in a rotating drum

    NASA Astrophysics Data System (ADS)

    Ratnesar-Shumate, Shanna; Pan, Yong-Le; Hill, Steven C.; Kinahan, Sean; Corson, Elizabeth; Eshbaugh, Jonathan; Santarpia, Joshua L.

    2015-03-01

    Biological aerosols (bioaerosols) released into the environment may undergo physical and chemical transformations when exposed to atmospheric constituents such as solar irradiation, reactive oxygenated species, ozone, free radicals, water vapor and pollutants. Aging experiments were performed in a rotating drum chamber subjecting bioaerosols, Bacillus thuringiensis Al Hakam (BtAH) spores and MS2 bacteriophages to ozone at 0 and 150 ppb, and relative humidities (RH) at 10%, 50%, and 80+%. Fluorescence spectra and intensities of the aerosols as a function of time in the reaction chamber were measured with a single particle fluorescence spectrometer (SPFS) and an Ultra-Violet Aerodynamic Particle Sizer® Spectrometer (UV-APS). Losses in biological activity were measured by culture and quantitative polymerase chain reaction (q-PCR) assay. For both types of aerosols the largest change in fluorescence emission was between 280 and 400 nm when excited at 263 nm followed by fluorescence emission between 380 and 700 nm when excited at 351 nm. The fluorescence for both BtAH and MS2 were observed to decrease significantly at high ozone concentration and high RH when excited at 263 nm excitation. The decreases in 263 nm excited fluorescence are indicative of hydrolysis and oxidation of tryptophan in the aerosols. Fluorescence measured with the UV-APS (355-nm excitation) increased with time for both BtAH and MS2 aerosols. A two log loss of MS2 bacteriophage infectivity was observed in the presence of ozone at ~50% and 80% RH when measured by culture and normalized for physical losses by q-PCR. Viability of BtAH spores after exposure could not be measured due to the loss of genomic material during experiments, suggesting degradation of extracelluar DNA attributable to oxidation. The results of these studies indicate that the physical and biological properties of bioaerosols change significantly after exposure to ozone and water vapor.

  19. Fluorescence spectra and biological activity of aerosolized bacillus spores and MS2 bacteriophage exposed to ozone at different relative humidities in a rotating drum

    DOE PAGES

    Ratnesar-Shumate, Shanna; Pan, Yong-Le; Hill, Steven C.; Kinahan, Sean; Corson, Elizabeth; Eshbaugh, Jonathan; Santarpia, Joshua L.

    2015-10-14

    Biological aerosols (bioaerosols) released into the environment may undergo physical and chemical transformations when exposed to atmospheric constituents such as solar irradiation, reactive oxygenated species, ozone, free radicals, water vapor and pollutants. Aging experiments were performed in a rotating drum chamber subjecting bioaerosols, Bacillus thuringiensis Al Hakam (BtAH) spores and MS2 bacteriophages to ozone at 0 and 150 ppb, and relative humidities (RH) at 10%, 50%, and 80+%. Fluorescence spectra and intensities of the aerosols as a function of time in the reaction chamber were measured with a single particle fluorescence spectrometer (SPFS) and an Ultra-Violet Aerodynamic Particle Sizer® Spectrometermore » (UV-APS). Losses in biological activity were measured by culture and quantitative polymerase chain reaction (q-PCR) assay. For both types of aerosols the largest change in fluorescence emission was between 280 and 400 nm when excited at 263 nm followed by fluorescence emission between 380 and 700 nm when excited at 351 nm. The fluorescence for both BtAH and MS2 were observed to decrease significantly at high ozone concentration and high RH when excited at 263 nm excitation. The decreases in 263 nm excited fluorescence are indicative of hydrolysis and oxidation of tryptophan in the aerosols. Fluorescence measured with the UV-APS (355-nm excitation) increased with time for both BtAH and MS2 aerosols. A two log loss of MS2 bacteriophage infectivity was observed in the presence of ozone at ~50% and 80% RH when measured by culture and normalized for physical losses by q-PCR. Viability of BtAH spores after exposure could not be measured due to the loss of genomic material during experiments, suggesting degradation of extracelluar DNA attributable to oxidation. The results of these studies indicate that the physical and biological properties of bioaerosols change significantly after exposure to ozone and water vapor.« less

  20. Fluorescence spectra and biological activity of aerosolized bacillus spores and MS2 bacteriophage exposed to ozone at different relative humidities in a rotating drum

    SciTech Connect

    Ratnesar-Shumate, Shanna; Pan, Yong-Le; Hill, Steven C.; Kinahan, Sean; Corson, Elizabeth; Eshbaugh, Jonathan; Santarpia, Joshua L.

    2015-10-14

    Biological aerosols (bioaerosols) released into the environment may undergo physical and chemical transformations when exposed to atmospheric constituents such as solar irradiation, reactive oxygenated species, ozone, free radicals, water vapor and pollutants. Aging experiments were performed in a rotating drum chamber subjecting bioaerosols, Bacillus thuringiensis Al Hakam (BtAH) spores and MS2 bacteriophages to ozone at 0 and 150 ppb, and relative humidities (RH) at 10%, 50%, and 80+%. Fluorescence spectra and intensities of the aerosols as a function of time in the reaction chamber were measured with a single particle fluorescence spectrometer (SPFS) and an Ultra-Violet Aerodynamic Particle Sizer® Spectrometer (UV-APS). Losses in biological activity were measured by culture and quantitative polymerase chain reaction (q-PCR) assay. For both types of aerosols the largest change in fluorescence emission was between 280 and 400 nm when excited at 263 nm followed by fluorescence emission between 380 and 700 nm when excited at 351 nm. The fluorescence for both BtAH and MS2 were observed to decrease significantly at high ozone concentration and high RH when excited at 263 nm excitation. The decreases in 263 nm excited fluorescence are indicative of hydrolysis and oxidation of tryptophan in the aerosols. Fluorescence measured with the UV-APS (355-nm excitation) increased with time for both BtAH and MS2 aerosols. A two log loss of MS2 bacteriophage infectivity was observed in the presence of ozone at ~50% and 80% RH when measured by culture and normalized for physical losses by q-PCR. Viability of BtAH spores after exposure could not be measured due to the loss of genomic material during experiments, suggesting degradation of extracelluar DNA attributable to oxidation. The results of these studies indicate that the physical and biological properties of bioaerosols change significantly after exposure to ozone and water vapor.

  1. [Elevated gastric lesions].

    PubMed

    de Careaga, B; Villagómez, G; Pabón, J; Calderón, O; Elío, D; Pérez, J; Martínez, M; Patiño, F; Ponce, R; Lora, J

    1986-01-01

    Elevated gastric lesions, represent an important group among gastric pathology. To establish its incidence in our experience, we studied the endoscopic reports of two important hospitals in La Paz city: Instituto de Gastroenterología Boliviano Japonés and Hospital Obrero No. 1. In order to make a good endoscopic diagnosis among different elevated lesions we use some parameters like: location, shape, size, diameter, surface of the lesion and surrounding mucosa and characteristics of the falls. 10.472 endoscopic reports were reviewed, 497 elevated gastric lesions were found, 475 corresponded to mucosal lesions (352 benign lesions and 123 malignant lesions), 11 to submucosal and 11 extragastric lesions.

  2. Nerve lesioning with direct current

    NASA Astrophysics Data System (ADS)

    Ravid, E. Natalie; Shi Gan, Liu; Todd, Kathryn; Prochazka, Arthur

    2011-02-01

    Spastic hypertonus (muscle over-activity due to exaggerated stretch reflexes) often develops in people with stroke, cerebral palsy, multiple sclerosis and spinal cord injury. Lesioning of nerves, e.g. with phenol or botulinum toxin is widely performed to reduce spastic hypertonus. We have explored the use of direct electrical current (DC) to lesion peripheral nerves. In a series of animal experiments, DC reduced muscle force by controlled amounts and the reduction could last several months. We conclude that in some cases controlled DC lesioning may provide an effective alternative to the less controllable molecular treatments available today.

  3. The 3 Ms Chandra campaign on Sgr A*: a census of X-ray flaring activity from the Galactic center

    NASA Astrophysics Data System (ADS)

    Neilsen, J.; Nowak, M. A.; Gammie, C.; Dexter, J.; Markoff, S.; Haggard, D.; Nayakshin, S.; Wang, Q. D.; Grosso, N.; Porquet, D.; Tomsick, J. A.; Degenaar, N.; Fragile, P. C.; Houck, J. C.; Wijnands, R.; Miller, J. M.; Baganoff, F. K.

    2014-05-01

    Over the last decade, X-ray observations of Sgr A* have revealed a black hole in a deep sleep, punctuated roughly once per day by brief flares. The extreme X-ray faintness of this supermassive black hole has been a long-standing puzzle in black hole accretion. To study the accretion processes in the Galactic center, Chandra (in concert with numerous ground- and space-based observatories) undertook a 3 Ms campaign on Sgr A* in 2012. With its excellent observing cadence, sensitivity, and spectral resolution, this Chandra X-ray Visionary Project (XVP) provides an unprecedented opportunity to study the behavior of the closest supermassive black hole. We present a progress report from our ongoing study of X-ray flares, including the brightest flare ever seen from Sgr A*. Focusing on the statistics of the flares and the quiescent emission, we discuss the physical implications of X-ray variability in the Galactic center.

  4. Quercetin inhibits AMPK/TXNIP activation and reduces inflammatory lesions to improve insulin signaling defect in the hypothalamus of high fructose-fed rats.

    PubMed

    Zhang, Qing-Yu; Pan, Ying; Wang, Rong; Kang, Lin-Lin; Xue, Qiao-Chu; Wang, Xiao-Ning; Kong, Ling-Dong

    2014-04-01

    Fructose is a nutritional composition of fruits and honey. Its excess consumption induces insulin resistance-associated metabolic diseases. Hypothalamic insulin signaling plays a pivotal role in controlling whole-body insulin sensitivity and energy homeostasis. Quercetin, a natural flavonoid, has been reported to ameliorate high fructose-induced rat insulin resistance and hyperlipidemia. In this study, we investigated its regulatory effects on the hypothalamus of high fructose-fed rats. Rats were fed 10% fructose in drinking water for 10 weeks. After 4 weeks, these animals were orally treated with quercetin (50 and 100 mg/kg), allopurinol (5 mg/kg) and water daily for the next 6 weeks, respectively. Quercetin effectively restored high fructose-induced hypothalamic insulin signaling defect by up-regulating the phosphorylation of insulin receptor and protein kinase B. Furthermore, quercetin was found to reduce metabolic nutrient sensors adenosine monophosphate-activated protein kinase (AMPK) activation and thioredoxin-interacting protein (TXNIP) overexpression, as well as the glutamine-glutamate cycle dysfunction in the hypothalamus of high fructose-fed rats. Subsequently, it ameliorated high fructose-caused hypothalamic inflammatory lesions in rats by suppressing the activation of hypothalamic nuclear factor κB (NF-κB) pathway and NOD-like receptor 3 (NLRP3) inflammasome with interleukin 1β maturation. Allopurinol had similar effects. These results provide in vivo evidence that quercetin-mediated down-regulation of AMPK/TXNIP and subsequent inhibition of NF-κB pathway/NLRP3 inflammasome activation in the hypothalamus of rats may be associated with the reduction of hypothalamic inflammatory lesions, contributing to the improvement of hypothalamic insulin signaling defect in this model. Thus, quercetin with the central activity may be a therapeutic for high fructose-induced insulin resistance and hyperlipidemia in humans.

  5. The functional organization of trial-related activity in lexical processing after early left hemispheric brain lesions: An event-related fMRI study

    PubMed Central

    Fair, Damien A.; Choi, Alexander H.; Dosenbach, Yannic B.L.; Coalson, Rebecca S.; Miezin, Francis M.; Petersen, Steven E.; Schlaggar, Bradley L.

    2009-01-01

    Children with congenital left hemisphere damage due to perinatal stroke are capable of acquiring relatively normal language functions despite experiencing a cortical insult that in adults often leads to devastating lifetime disabilities. Although this observed phenomenon accepted, its neurobiological mechanisms are not well characterized. In this paper we examined the functional neuroanatomy of lexical processing in 13 children/adolescents with perinatal left hemispheric damage. In contrast to many previous perinatal infarct fMRI studies, we use an event-related design, which allowed us to isolate trial related activity and examine correct and error trials separately. Using both group and single subject analysis techniques we attempt to address several methodological factors that may contribute to some discrepancies in the perinatal lesion literature. These methodological factors include making direct statistical comparisons, using common stereotactic space, using both single-subject and group analyses, and accounting for performance differences. Our group analysis, investigating correct trial related activity (separately from error trials), showed very few statistical differences in the non-involved right hemisphere between patients and performance matched controls. The single subject analysis revealed atypical regional activation patterns in several patients; however, the location of these regions identified in individual patients often varied across subjects. These results are consistent with the idea that alternative functional organization of trial-related activity after left hemisphere lesions is in large part unique to the individual. In addition, reported differences between results obtained with event-related designs and blocked designs may suggest diverging organizing principles for sustained and trial-related activity after early childhood brain injuries. PMID:19819000

  6. Development and validation of an LC-MS/MS method for simultaneous determination of piperaquine and 97-63, the active metabolite of CDRI 97-78, in rat plasma and its application in interaction study.

    PubMed

    Wahajuddin, Muhammad; Singh, Sheelendra Pratap; Taneja, Isha; Raju, Kanumuri Siva Rama; Gayen, Jiaur Rahman; Siddiqui, Hefazat Hussain; Singh, Shio Kumar

    2016-02-01

    Piperaquine-dihydroartemisinin combination is the latest addition to the repertoire of ACTs recommended by the World Health Organization (WHO) for treatment of falciparum malaria. Due to the increasing resistance to artemisinin derivatives, CSIR-CDRI has developed a prospective short acting, trioxane antimalarial derivative, CDRI 97-78. In the present study, a liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method for the simultaneous quantification of piperaquine (PPQ) and 97-63, the active metabolite of CDRI 97-78 found in vivo, was developed and validated in 100 μL rat plasma using halofantrine as internal standard. PPQ and 97-63 were separated using acetonitrile:methanol (50:50, v/v) and ammonium formate buffer (10 mM, pH 4.5) in the ratio of 95:5(v/v) as mobile phase under isocratic conditions at a flow rate of 0.65 mL/min on Waters Atlantis C18 (4.6 × 50 mm, 5.0 µm) column. The extraction recoveries of PPQ and 97-63 ranged from 90.58 to 105.48%, while for the internal standard, it was 94.27%. The method was accurate and precise in the linearity range 3.9-250 ng/mL for both the analytes, with a correlation coefficient (r) of ≥ 0.998. The intra- and inter-day assay precision ranged from 2.91 to 8.45% and; intra- and inter-day assay accuracy was between 92.50 and 110.20% for both the analytes. The method was successfully applied to study the effect of oral co-administration of PPQ on the pharmacokinetics of CDRI 97-78 in Sprague-dawley rats and vice versa. The co-administration of CDRI 97-78 caused significant decrease in AUC0-∞ of PPQ from 31.52 ± 2.68 to 14.84 ± 4.33 h*µg/mL. However, co-administration of PPQ did not have any significant effect on the pharmacokinetics of CDRI 97-78. PMID:25975936

  7. Gastroprotective Activity of Polygonum chinense Aqueous Leaf Extract on Ethanol-Induced Hemorrhagic Mucosal Lesions in Rats.

    PubMed

    Ismail, Iza Farhana; Golbabapour, Shahram; Hassandarvish, Pouya; Hajrezaie, Maryam; Abdul Majid, Nazia; Kadir, Farkaad A; Al-Bayaty, Fouad; Awang, Khalijah; Hazni, Hazrina; Abdulla, Mahmood Ameen

    2012-01-01

    Polygonum chinense is a Malaysian ethnic plant with various healing effects. This study was to determine preventive effect of aqueous leaf extract of P. chinense against ethanol-induced gastric mucosal injury in rats. Sprague Dawley rats were divided into seven groups. The normal and ulcer control groups were orally administered with distilled water. The reference group was orally administered with 20 mg/kg omeprazole. The experimental groups received the extracts 62.5, 125, 250, and 500 mg/kg, accordingly. After sixty minutes, distilled water and absolute ethanol were given (5 mL/kg) to the normal control and the others, respectively. In addition to histology, immunohistochemical and periodic acid schiff (PAS) stains, levels of lipid peroxidation, malondialdehyde (MDA), antioxidant enzymes, and superoxide dismutase (SOD) were measured. The ulcer group exhibited severe mucosal damages. The experimental groups significantly reduced gastric lesions and MDA levels and increased SOD level. Immunohistochemistry of the experimental groups showed upregulation and downregulation of Hsp70 and Bax proteins, respectively. PAS staining in these groups exhibited intense staining as compared to the ulcer group. Acute toxicity study revealed the nontoxic nature of the extract. Our data provide first evidence that P. chinense extract could significantly prevent gastric ulcer.

  8. Gastroprotective activity of isopulegol on experimentally induced gastric lesions in mice: investigation of possible mechanisms of action.

    PubMed

    Silva, Maria Izabel Gomes; Moura, Brinell Arcanjo; Neto, Manuel Rufino de Aquino; Tomé, Adriana da Rocha; Rocha, Nayrton Flávio Moura; de Carvalho, Alyne Mara Rodrigues; Macêdo, Danielle Silveira; Vasconcelos, Silvânia Maria Mendes; de Sousa, Damião Pergentino; Viana, Glauce Socorro de Barros; de Sousa, Francisca Cléa Florenço

    2009-09-01

    The present study investigated whether isopulegol, a monoterpene present in essential oils of several aromatic plants, would be able to promote some gastroprotective effect and also verified the possible mechanisms involved in this action. For this study, ethanol- and indomethacin-induced gastric ulcer models in mice and histopathological assessment were used. The roles of NO, sulfhydryls (glutathione, GSH), ATP-sensitive K(+) channels (K(ATP) channels), and prostaglandins were also investigated. Isopulegol exhibited a dose-related gastroprotective effect against ethanol-induced lesions, while the pretreatment with glibenclamide and indomethacin [but not with N(G)-nitro-L-arginine methyl ester] were able to reverse this action. The pretreatment with isopulegol also restored GSH levels to normal levels and exhibited dose-related gastroprotective effect against indomethacin-induced ulcer. The results suggested that isopulegol presents significant gastroprotective effects in both ethanol- and indomethacin-induced ulcer models, which appear to be mediated, at least in part, by endogenous prostaglandins, K(ATP) channel opening, and antioxidant properties. PMID:19479241

  9. Gastroprotective Activity of Polygonum chinense Aqueous Leaf Extract on Ethanol-Induced Hemorrhagic Mucosal Lesions in Rats

    PubMed Central

    Ismail, Iza Farhana; Abdul Majid, Nazia; Kadir, Farkaad A.; Al-Bayaty, Fouad; Awang, Khalijah

    2012-01-01

    Polygonum chinense is a Malaysian ethnic plant with various healing effects. This study was to determine preventive effect of aqueous leaf extract of P. chinense against ethanol-induced gastric mucosal injury in rats. Sprague Dawley rats were divided into seven groups. The normal and ulcer control groups were orally administered with distilled water. The reference group was orally administered with 20 mg/kg omeprazole. The experimental groups received the extracts 62.5, 125, 250, and 500 mg/kg, accordingly. After sixty minutes, distilled water and absolute ethanol were given (5 mL/kg) to the normal control and the others, respectively. In addition to histology, immunohistochemical and periodic acid schiff (PAS) stains, levels of lipid peroxidation, malondialdehyde (MDA), antioxidant enzymes, and superoxide dismutase (SOD) were measured. The ulcer group exhibited severe mucosal damages. The experimental groups significantly reduced gastric lesions and MDA levels and increased SOD level. Immunohistochemistry of the experimental groups showed upregulation and downregulation of Hsp70 and Bax proteins, respectively. PAS staining in these groups exhibited intense staining as compared to the ulcer group. Acute toxicity study revealed the nontoxic nature of the extract. Our data provide first evidence that P. chinense extract could significantly prevent gastric ulcer. PMID:23365597

  10. The 4 Ms CHANDRA Deep Field-South Number Counts Apportioned by Source Class: Pervasive Active Galactic Nuclei and the Ascent of Normal Galaxies

    NASA Technical Reports Server (NTRS)

    Lehmer, Bret D.; Xue, Y. Q.; Brandt, W. N.; Alexander, D. M.; Bauer, F. E.; Brusa, M.; Comastri, A.; Gilli, R.; Hornschemeier, A. E.; Luo, B.; Paolillo, M.; Ptak, A.; Shemmer, O.; Schneider, D. P.; Tozzi, P.; Vignali, C.

    2012-01-01

    We present 0.5-2 keV, 2-8 keV, 4-8 keV, and 0.5-8 keV (hereafter soft, hard, ultra-hard, and full bands, respectively) cumulative and differential number-count (log N-log S ) measurements for the recently completed approx. equal to 4 Ms Chandra Deep Field-South (CDF-S) survey, the deepest X-ray survey to date. We implement a new Bayesian approach, which allows reliable calculation of number counts down to flux limits that are factors of approx. equal to 1.9-4.3 times fainter than the previously deepest number-count investigations. In the soft band (SB), the most sensitive bandpass in our analysis, the approx. equal to 4 Ms CDF-S reaches a maximum source density of approx. equal to 27,800 deg(sup -2). By virtue of the exquisite X-ray and multiwavelength data available in the CDF-S, we are able to measure the number counts from a variety of source populations (active galactic nuclei (AGNs), normal galaxies, and Galactic stars) and subpopulations (as a function of redshift, AGN absorption, luminosity, and galaxy morphology) and test models that describe their evolution. We find that AGNs still dominate the X-ray number counts down to the faintest flux levels for all bands and reach a limiting SB source density of approx. equal to 14,900 deg(sup -2), the highest reliable AGN source density measured at any wavelength. We find that the normal-galaxy counts rise rapidly near the flux limits and, at the limiting SB flux, reach source densities of approx. equal to 12,700 deg(sup -2) and make up 46% plus or minus 5% of the total number counts. The rapid rise of the galaxy counts toward faint fluxes, as well as significant normal-galaxy contributions to the overall number counts, indicates that normal galaxies will overtake AGNs just below the approx. equal to 4 Ms SB flux limit and will provide a numerically significant new X-ray source population in future surveys that reach below the approx. equal to 4 Ms sensitivity limit. We show that a future approx. equal to 10 Ms CDF

  11. Deconstruction of activity-dependent covalent modification of heme in human neutrophil myeloperoxidase by multistage mass spectrometry (MS(4)).

    PubMed

    Geoghegan, Kieran F; Varghese, Alison H; Feng, Xidong; Bessire, Andrew J; Conboy, James J; Ruggeri, Roger B; Ahn, Kay; Spath, Samantha N; Filippov, Sergey V; Conrad, Steven J; Carpino, Philip A; Guimarães, Cristiano R W; Vajdos, Felix F

    2012-03-13

    Myeloperoxidase (MPO) is known to be inactivated and covalently modified by treatment with hydrogen peroxide and agents similar to 3-(2-ethoxypropyl)-2-thioxo-2,3-dihydro-1H-purin-6(9H)-one (1), a 254.08 Da derivative of 2-thioxanthine. Peptide mapping by liquid chromatography and mass spectrometry detected modification by 1 in a labile peptide-heme-peptide fragment of the enzyme, accompanied by a mass increase of 252.08 Da. The loss of two hydrogen atoms was consistent with mechanism-based oxidative coupling. Multistage mass spectrometry (MS(4)) of the modified fragment in an ion trap/Orbitrap spectrometer demonstrated that 1 was coupled directly to heme. Use of a 10 amu window delivered the full isotopic envelope of each precursor ion to collision-induced dissociation, preserving definitive isotopic profiles for iron-containing fragments through successive steps of multistage mass spectrometry. Iron isotope signatures and accurate mass measurements supported the structural assignments. Crystallographic analysis confirmed linkage between the methyl substituent of the heme pyrrole D ring and the sulfur atom of 1. The final orientation of 1 perpendicular to the plane of the heme ring suggested a mechanism consisting of two consecutive one-electron oxidations of 1 by MPO. Multistage mass spectrometry using stage-specific collision energies permits stepwise deconstruction of modifications of heme enzymes containing covalent links between the heme group and the polypeptide chain.

  12. Chemical quantification and antioxidant assay of four active components in Ficus hirta root using UPLC-PAD-MS fingerprinting combined with cluster analysis

    PubMed Central

    2013-01-01

    Background Root of Ficus hirta (RFH) is widely consumed in China as a plant-derived popular food. However, contents of the active constituents of RFH are unknown, and the chemical as well as bioactive properties of RFH may be affected by growing area. In order to ensure the standard efficacy of health products made with RFH, its active constituents should firstly be determined and, secondly, a means of assessing samples for their contents of these constituents is needed. Results Four active components, including two coumarins, namely psoralen and bergapten, and two flavonoids, namely luteolin and apigenin, in twenty RFH samples were quantified using a new ultra performance liquid chromatography coupled with photodiode array detector and mass spectrometry (UPLC-PAD-MS) method, and the content level in descending order was psoralen > bergapten > luteolin > apigenin. Chromatographic fingerprint similarity evaluation and cluster analysis were used to assess geographical origin of RFH, and the results revealed a high level of similarity for the tested RFH samples obtained from Hainan, Guangdong, Guangxi provinces and Hong Kong. 2, 2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay was conducted to evaluate the antioxidant potencies of the four components, and the results clearly demonstrated that luteolin was most effective; apigenin exhibited a moderate potency, whereas psoralen and bergapten possessed little effect against free radical reactions. Structure-activity relationship of the components was elucidated, and the 3′-hydroxyl group of luteolin was found to be directly responsible for its antioxidant activity. Conclusion The present UPLC-PAD-MS method and DPPH radical scavenging assay performed well for the purpose of constituent quantification and antioxidant assay. Global profiles were highly similar for RFH samples from different origins. Both the coumarins and flavonoids were involved in the health benefit of RFH. PMID:23835498

  13. The Effect of the More Active MuMs in Stirling Trial on Body Composition and Psychological Well-Being among Postnatal Women.

    PubMed

    Lee, Alyssa S; McInnes, Rhona J; Hughes, Adrienne R; Guthrie, Wendy; Jepson, Ruth

    2016-01-01

    Introduction. Physical activity is important for health and well-being; however, rates of postnatal physical activity can be low. This paper reports the secondary outcomes of a trial aimed at increasing physical activity among postnatal women. Methods. More Active MuMs in Stirling (MAMMiS) was a randomised controlled trial testing the effect of physical activity consultation and pram walking group intervention among inactive postnatal women. Data were collected on postnatal weight, body composition, general well-being, and fatigue. Participants were also interviewed regarding motivations and perceived benefits of participating in the trial. Results. There was no significant effect of the intervention on any weight/body composition outcome or on general well-being at three or six months of follow-up. There was a significant but inconsistent difference in fatigue between groups. Qualitative data highlighted a number of perceived benefits to weight, body composition, and particularly well-being (including improved fatigue) which were not borne out by objective data. Discussion. The MAMMiS study found no impact of the physical activity intervention on body composition and psychological well-being and indicates that further research is required to identify successful approaches to increase physical activity and improve health and well-being among postnatal women.

  14. The Effect of the More Active MuMs in Stirling Trial on Body Composition and Psychological Well-Being among Postnatal Women

    PubMed Central

    Jepson, Ruth

    2016-01-01

    Introduction. Physical activity is important for health and well-being; however, rates of postnatal physical activity can be low. This paper reports the secondary outcomes of a trial aimed at increasing physical activity among postnatal women. Methods. More Active MuMs in Stirling (MAMMiS) was a randomised controlled trial testing the effect of physical activity consultation and pram walking group intervention among inactive postnatal women. Data were collected on postnatal weight, body composition, general well-being, and fatigue. Participants were also interviewed regarding motivations and perceived benefits of participating in the trial. Results. There was no significant effect of the intervention on any weight/body composition outcome or on general well-being at three or six months of follow-up. There was a significant but inconsistent difference in fatigue between groups. Qualitative data highlighted a number of perceived benefits to weight, body composition, and particularly well-being (including improved fatigue) which were not borne out by objective data. Discussion. The MAMMiS study found no impact of the physical activity intervention on body composition and psychological well-being and indicates that further research is required to identify successful approaches to increase physical activity and improve health and well-being among postnatal women. PMID:27610245

  15. The Effect of the More Active MuMs in Stirling Trial on Body Composition and Psychological Well-Being among Postnatal Women.

    PubMed

    Lee, Alyssa S; McInnes, Rhona J; Hughes, Adrienne R; Guthrie, Wendy; Jepson, Ruth

    2016-01-01

    Introduction. Physical activity is important for health and well-being; however, rates of postnatal physical activity can be low. This paper reports the secondary outcomes of a trial aimed at increasing physical activity among postnatal women. Methods. More Active MuMs in Stirling (MAMMiS) was a randomised controlled trial testing the effect of physical activity consultation and pram walking group intervention among inactive postnatal women. Data were collected on postnatal weight, body composition, general well-being, and fatigue. Participants were also interviewed regarding motivations and perceived benefits of participating in the trial. Results. There was no significant effect of the intervention on any weight/body composition outcome or on general well-being at three or six months of follow-up. There was a significant but inconsistent difference in fatigue between groups. Qualitative data highlighted a number of perceived benefits to weight, body composition, and particularly well-being (including improved fatigue) which were not borne out by objective data. Discussion. The MAMMiS study found no impact of the physical activity intervention on body composition and psychological well-being and indicates that further research is required to identify successful approaches to increase physical activity and improve health and well-being among postnatal women. PMID:27610245

  16. The Effect of the More Active MuMs in Stirling Trial on Body Composition and Psychological Well-Being among Postnatal Women

    PubMed Central

    Jepson, Ruth

    2016-01-01

    Introduction. Physical activity is important for health and well-being; however, rates of postnatal physical activity can be low. This paper reports the secondary outcomes of a trial aimed at increasing physical activity among postnatal women. Methods. More Active MuMs in Stirling (MAMMiS) was a randomised controlled trial testing the effect of physical activity consultation and pram walking group intervention among inactive postnatal women. Data were collected on postnatal weight, body composition, general well-being, and fatigue. Participants were also interviewed regarding motivations and perceived benefits of participating in the trial. Results. There was no significant effect of the intervention on any weight/body composition outcome or on general well-being at three or six months of follow-up. There was a significant but inconsistent difference in fatigue between groups. Qualitative data highlighted a number of perceived benefits to weight, body composition, and particularly well-being (including improved fatigue) which were not borne out by objective data. Discussion. The MAMMiS study found no impact of the physical activity intervention on body composition and psychological well-being and indicates that further research is required to identify successful approaches to increase physical activity and improve health and well-being among postnatal women.

  17. BG-12 reduces evolution of new enhancing lesions to T1-hypointense lesions in patients with multiple sclerosis.

    PubMed

    MacManus, D G; Miller, D H; Kappos, L; Gold, R; Havrdova, E; Limmroth, V; Polman, C H; Schmierer, K; Yousry, T A; Eraksoy, M; Meluzinova, E; Dufek, M; Yang, M; O'Neill, G N; Dawson, K

    2011-03-01

    BG-12, an immunomodulatory agent, reduces frequency of new gadolinium-enhancing (Gd+) lesions in relapsing multiple sclerosis (MS). This study reports the effect of 240 mg BG-12 orally three times daily (tid) for 24 weeks on the evolution of new Gd+ lesions to T1-hypointense lesions. Brain magnetic resonance imaging (MRI) scans from patients in placebo and 240 mg BG-12 tid arms of a phase 2b study were examined retrospectively. Included patients had at least one new Gd+ lesion from weeks 4 to 12. Week 24 scans were analyzed for number and proportion of new Gd+ lesions that evolved to T1-hypointense lesions. Eighteen patients receiving BG-12 and 38 patients receiving placebo were included in the analysis. The analysis tracked 147 new Gd+ lesions in patients from the BG-12 group and 221 Gd+ lesions in patients from the placebo group. The percentage of Gd+ lesions that evolved to T1-hypointense lesions was 34% lower with BG-12 treatment versus placebo (29%, BG-12; 44%, placebo; odds ratio 0.51; 95% confidence interval 0.43, 0.61; p < 0.0001). In addition to reducing frequency of new Gd+ lesions, BG-12 significantly reduced probability of their evolution to T1-hypointense lesions in patients with MS compared with placebo.

  18. Voxel-Based Lesion Symptom Mapping of Coarse Coding and Suppression Deficits in Patients With Right Hemisphere Damage

    PubMed Central

    Tompkins, Connie A.; Meigh, Kimberly M.; Prat, Chantel S.

    2015-01-01

    Purpose This study examined right hemisphere (RH) neuroanatomical correlates of lexical–semantic deficits that predict narrative comprehension in adults with RH brain damage. Coarse semantic coding and suppression deficits were related to lesions by voxel-based lesion symptom mapping. Method Participants were 20 adults with RH cerebrovascular accidents. Measures of coarse coding and suppression deficits were computed from lexical decision reaction times at short (175 ms) and long (1000 ms) prime-target intervals. Lesions were drawn on magnetic resonance imaging images and through normalization were registered on an age-matched brain template. Voxel-based lesion symptom mapping analysis was applied to build a general linear model at each voxel. Z score maps were generated for each deficit, and results were interpreted using automated anatomical labeling procedures. Results A deficit in coarse semantic activation was associated with lesions to the RH posterior middle temporal gyrus, dorsolateral prefrontal cortex, and lenticular nuclei. A maintenance deficit for coarsely coded representations involved the RH temporal pole and dorsolateral prefrontal cortex more medially. Ineffective suppression implicated lesions to the RH inferior frontal gyrus and subcortical regions, as hypothesized, along with the rostral temporal pole. Conclusion Beyond their scientific implications, these lesion–deficit correspondences may help inform the clinical diagnosis and enhance decisions about candidacy for deficit-focused treatment to improve narrative comprehension in individuals with RH damage. PMID:26425785

  19. Neoplastic lesions of the human liver in relation to the activity of the cytochrome P-450 dependent monooxygenase system.

    PubMed

    Plewka, D; Plewka, A; Nowaczyk, G; Kamiński, M; Rutkowski, T; Ludyga, T; Ziaja, K

    2000-01-01

    We studied the activity of Mixed function oxidase (MFO) in human livers affected by cancer. We determined the content of cytochrome P-450 and b5, as well as the activity of their corresponding reductases, according to generally accepted methods. Liver fragments corresponding with a) healthy tissue, b) tissue at the cancer border and, c) cancerous tissue were collected during surgery from patients with liver cancer. We noted that the developing liver cancer decreased the level of cytochrome P-450, even by a magnitude order. The activity of its corresponding reductase was higher in cancerous than in healthy tissues. Cytochrome b5 behaved in an analogous manner, although the decrease in its content was less significant. NADH-cytochrome b5 reductase activity changes were insignificant.

  20. Study and determination of elemental impurities by ICP-MS in active pharmaceutical ingredients using single reaction chamber digestion in compliance with USP requirements.

    PubMed

    Muller, Aline L H; Oliveira, Jussiane S S; Mello, Paola A; Muller, Edson I; Flores, Erico M M

    2015-05-01

    In this work a method for active pharmaceutical ingredients (APIs) digestion using the single reaction chamber (SRC-UltraWave™) system was proposed following the new recommendations of United States Pharmacopeia (USP). Levodope (LEVO), primaquine diphosphate (PRIM), propranolol hydrochloride (PROP) and sulfamethoxazole (SULF) were used to evaluate the digestion efficiency of the proposed method. A comparison of digestion efficiency was performed by measuring the carbon content and residual acidity in digests obtained using SRC and in digests obtained using conventional microwave-assisted digestion system (Multiwave(TM)). Three digestion solutions (concentrated HNO3, aqua regia or inverse aqua regia) were evaluated for digestion of APIs. The determination of Cd, Ir, Mn, Mo, Ni, Os, Pb, Pd, Pt, Rh, Ru was performed using inductively coupled plasma mass spectrometry (ICP-MS) in standard mode. Dynamic reaction cell (DRC) mode was used for the determination of (51)V, (52)Cr, (53)Cr, (63)Cu and (65)Cu in order to solve polyatomic ion interferences. Arsenic and Hg were determined using chemical vapor generation coupled to ICP-MS (FI-CVG-ICP-MS). Masses of 500mg of APIs were efficiently digested in a SRC-UltraWave™ system using only HNO3 and allowing a carbon content lower than 250mg L(-1) in final digests. Inverse aqua regia was suitable for digestion of sample masses up to 250mg allowing the determination of Ir, Pd, Pt, Rh and Ru. By using HNO3 or inverse aqua regia, suitable recoveries were obtained (between 91 and 109%) for all analytes (exception for Os). Limits of quantification were in agreement with USP requirements and they ranged from 0.001 to 0.015µg g(-1) for all elemental impurities (exception for Os). The proposed method was suitable for elemental impurities determination in APIs and it can be used in routine analysis for quality control in pharmaceutical industries. PMID:25702998

  1. LC-MS profiling of N-alkylamides in Spilanthes acmella extract and the transmucosal behaviour of its main bio-active spilanthol.

    PubMed

    Boonen, J; Baert, B; Burvenich, C; Blondeel, P; De Saeger, S; De Spiegeleer, B

    2010-11-01

    N-Alkylamides are a promising group of naturally occurring bio-actives, with evidence for immune stimulating properties, which find applications i.a. in buccal preparations. In Spilanthes extracts, these properties are mainly ascribed to the most abundant N-isobutylamide, spilanthol. Yet, other N-alkylamides present in these extracts may contribute to this effect, as well as to its potential toxicity and physiologic interactions. Therefore, N-alkylamide profiling of an ethanolic Spilanthes extract was performed using a gradient reversed phase high performance liquid chromatography/electrospray ionization ion trap mass spectrometry (HPLC/ESI-MS) method on an embedded polar column. MS(1) and MS(2) fragmentation data were used for identification purposes. Moreover, the transmucosal behaviour of spilanthol, formulated in this ethanolic extract and in two commercially available oral gels, was evaluated using porcine buccal mucosa in a Franz diffusion cell experimental set-up. A high-throughput HPLC-UV method was used for the quantification of spilanthol in the receptor phase. Fundamental permeation characteristics of spilanthol in a solvent-independent way (100% aqueous dose solution) were obtained using different propylene glycol/water ratios. Eight N-isobutylamides, two 2-methylbutylamides and one 2-phenylethylamide were detected, with spilanthol as most abundant N-alkylamide (88.8%). Up till now, two of these N-isobutylamides were not yet described in Spilanthes extracts. We demonstrated for the first time that spilanthol permeates the buccal mucosa. Depending on the formulation, a more pronounced local or systemic effect is achieved, which is important for the regulatory product classification. The purely aqueous permeation coefficient K(p,aq) (+/-SEM) was found to be 11.3 (+/-0.403)10(-3)cm/h. PMID:20227845

  2. GC and GC/MS analysis of essential oil composition of the endemic Soqotraen Leucas virgata Balf.f. and its antimicrobial and antioxidant activities.

    PubMed

    Mothana, Ramzi A; Al-Said, Mansour S; Al-Yahya, Mohammed A; Al-Rehaily, Adnan J; Khaled, Jamal M

    2013-01-01

    Leucas virgata Balf.f. (Lamiaceae) was collected from the Island Soqotra (Yemen) and its essential oil was obtained by hydrodistillation. The chemical composition of the oil was investigated by GC and GC-MS. Moreover, the essential oil was evaluated for its antimicrobial activity against two Gram-positive bacteria, two Gram-negative bacteria, and one yeast species by using broth micro-dilution assay for minimum inhibitory concentrations (MIC) and antioxidant activity by measuring the scavenging activity of the DPPH radical. The investigation led to the identification of 43 constituents, representing 93.9% of the total oil. The essential oil of L. virgata was characterized by a high content of oxygenated monoterpenes (50.8%). Camphor (20.5%) exo-fenchol (3.4%), fenchon (5.4%), and borneol (3.1%) were identified as the main components. Oxygenated sesquiterpenes were found as the second major group of compounds (21.0%). β-Eudesmol (6.1%) and caryophyllene oxide (5.1%) were the major compounds among oxygenated sesquiterpenes. The results of the antimicrobial assay showed that the oil exhibited a great antibacterial activity against the tested S. aureus, B. subtilis, and E. coli. No activity was found against P. aeruginosa and C. albicans. Moreover, the DPPH-radical scavenging assay exhibited only a moderate antioxidant activity (31%) for the oil at the highest concentration tested (1 mg/mL). PMID:24284402

  3. High-resolution HDX-MS reveals distinct mechanisms of RNA recognition and activation by RIG-I and MDA5

    PubMed Central

    Zheng, Jie; Yong, Hui Yee; Panutdaporn, Nantika; Liu, Chuanfa; Tang, Kai; Luo, Dahai

    2015-01-01

    RIG-I and MDA5 are the major intracellular immune receptors that recognize viral RNA species and undergo a series of conformational transitions leading to the activation of the interferon-mediated antiviral response. However, to date, full-length RLRs have resisted crystallographic efforts and a molecular description of their activation pathways remains hypothetical. Here we employ hydrogen/deuterium exchange coupled with mass spectrometry (HDX-MS) to probe the apo states of RIG-I and MDA5 and to dissect the molecular details with respect to distinct RNA species recognition, ATP binding and hydrolysis and CARDs activation. We show that human RIG-I maintains an auto-inhibited resting state owing to the intra-molecular HEL2i-CARD2 interactions while apo MDA5 lacks the analogous intra-molecular interactions and therefore adopts an extended conformation. Our work demonstrates that RIG-I binds and responds differently to short triphosphorylated RNA and long duplex RNA and that sequential addition of RNA and ATP triggers specific allosteric effects leading to RIG-I CARDs activation. We also present a high-resolution protein surface mapping technique that refines the cooperative oligomerization model of neighboring MDA5 molecules on long duplex RNA. Taken together, our data provide a high-resolution view of RLR activation in solution and offer new evidence for the molecular mechanism of RLR activation. PMID:25539915

  4. Enhancing phytochemical levels, enzymatic and antioxidant activity of spinach leaves by chitosan treatment and an insight into the metabolic pathway using DART-MS technique.

    PubMed

    Singh, Shachi

    2016-05-15

    Phytochemicals are health promoting compounds, synthesized by the plants to protect them against biotic or abiotic stress. The metabolic pathways leading to the synthesis of these phytochemicals are highly inducible; therefore methods could be developed to enhance their production by the exogenous application of chemical inducers/elicitors. In the present experiment, chitosan was used as an elicitor molecule to improve the phytochemical content of spinach plant. When applied at a concentration of 0.01 mg/ml as a foliar spray, chitosan was able to cause an increase in the enzymatic (peroxidase, catalase and phenylalanine ammonium lyase (PAL)) and non enzymatic (total phenolics, flavonoids and proteins) defensive metabolites, as well as, in the total antioxidant activity of the spinach leaves. A 1.7-fold increase in the total phenolics, a 2-fold increase in total flavonoid and a 1.6-fold increase in total protein were achieved with the treatment. A higher level of enzymatic activity was observed with a 4-fold increase in peroxidase and approximately 3-fold increases in catalase and phenylalanine ammonium lyase activity. Antioxidant activity showed a positive correlation between phenolic compounds and the enzymatic activity. Direct analysis in real time mass spectrometry (DART-MS) was applied to generate the metabolite profile of control and treated leaves. DART analysis revealed the activation of phenylpropanoid pathway by chitosan molecule, targeting the synthesis of diverse classes of flavonoids and their glycosides. Important metabolites of stress response were also visible in the DART spectra, including proline and free sugars.

  5. Clinical and radiographical evaluation of the healing of large periapical lesions using triple antibiotic paste, photo activated disinfection and calcium hydroxide when used as root canal disinfectant

    PubMed Central

    Varughese, Jolly M.; Thomas, Kunjamma; Abraham, Aby; James, Elizabeth P.; Maroli, Ramesh K.

    2014-01-01

    Objectives: To evaluate clinically and radio graphically, the healing following nonsurgical treatment of periapical lesions when Photo Activated Disinfection(PAD), triple antibiotic paste and calcium hydroxide was used as root canal disinfectant. Material and Methods: Sixty patients (20 for PAD, 20 for triple antibiotic paste, 20 for calcium hydroxide) with periapical lesions in the maxillary and mandibular anterior region were selected from the outpatient section of the Department of Conservative Dentistry & Endodontics, Govt. Dental College, Kozhikode to participate in this study. The patients were selected with a preoperative score of 4 or 5. There were no significant differences for the PAI Scores between the three groups at the start of the experiment .Intracanal disinfection was done in the three groups followed by obturation. The patients recalled at 3,6,12,18 months interval. Results: At 18 months follow up 15 % of cases failed in calcium hydroxide group,5% in triple antibiotic paste and no failure cases were seen in PAD group. Success criteria were divided into strict and loose, while the former had statistically significant p value the latter did not. Kruskal-Wallis Test showed an increased mean value for PDT and a significant change in p value. Bonferroni post hoc test was done to compare if there is any significant change between groups. Only significant change was found between calcium hydroxide and photoactivated disinfection . Conclusion: PAD was more effective intracanal disinfectant at 6,12 and 18 months. Key words:Calcium, hydroxide, photo activated disinfection, triple antibiotic paste, root canal disinfection PMID:25136422

  6. NMR and GC-MS based metabolic profiling and free-radical scavenging activities of Cordyceps pruinosa mycelia cultivated under different media and light conditions.

    PubMed

    Oh, Taek-Joo; Hyun, Sun-Hee; Lee, Seul-Gi; Chun, Young-Jin; Sung, Gi-Ho; Choi, Hyung-Kyoon

    2014-01-01

    Variation of metabolic profiles in Cordyceps pruinosa mycelia cultivated under various media and light conditions was investigated using 1H nuclear magnetic resonance (NMR) analysis and gas chromatography mass spectrometry (GC-MS) with multivariate statistical analysis. A total of 71 metabolites were identified (5 alcohols, 21 amino acids, 15 organic acids, 4 purines, 3 pyrimidines, 7 sugars, 11 fatty acids, and 5 other metabolites) by NMR and GC-MS analysis. The mycelia grown in nitrogen media and under dark conditions showed the lowest growth and ergosterol levels, essential to a functional fungal cell membrane; these mycelia, however, had the highest levels of putrescine, which is involved in abiotic stress tolerance. In contrast, mycelia cultivated in sabouraud dextrose agar with yeast extract (SDAY) media and under light conditions contained relatively higher levels of fatty acids, including valeric acid, stearic acid, lignoceric acid, myristic acid, oleic acid, palmitoleic acid, hepadecenoic acid, and linoleic acid. These mycelia also had the highest phenolic content and antioxidant activity, and did not exhibit growth retardation due to enhanced asexual development caused by higher levels of linoleic acid. Therefore, we suggested that a light-enriched environment with SDAY media was more optimal than dark condition for cultivation of C. pruinosa mycelia as biopharmaceutical or nutraceutical resources.

  7. GC-MS Analysis: In Vivo Hepatoprotective and Antioxidant Activities of the Essential Oil of Achillea biebersteinii Afan. Growing in Saudi Arabia

    PubMed Central

    Al-Said, Mansour S.; Mothana, Ramzi A.; Al-Yahya, Mohammed M.; Rafatullah, Syed; Al-Sohaibani, Mohammed O.; Khaled, Jamal M.; Alatar, Abdulrahman; Alharbi, Naiyf S.; Kurkcuoglu, Mine; Baser, Husnu C.

    2016-01-01

    Liver disease is a worldwide problem. It represents one of the main causes of morbidity and mortality in humans. Achillea biebersteinii is used as herbal remedy for various ailments including liver diseases. But the scientific basis for its medicinal use remains unknown. Thus, this research was undertaken to evaluate the efficiency of A. biebersteinii essential oil (ABEO) (0.2 mL/kg) in the amelioration of CCl4-induced hepatotoxicity in rodent model. Moreover, the chemical content of the oil was investigated using GC and GC-MS. The following biochemical parameters were evaluated: serum glutamic oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), gamma-glutamyl-transpeptidase (γ-GGT), alkaline phosphatase (ALP), and total bilirubin. Furthermore, lipid profile, malondialdehyde (MDA), nonprotein sulfhydryl (NP-SH), and total protein (TP) contents in liver tissue were estimated. 44 components (92.0%) of the total oil have been identified by GC-MS analysis where α-terpinene and p-cymene were the most abundant. The high serum enzymatic (GOT, GPT, GGT, and ALP) and bilirubin concentrations as well as the level of MDA, NP-SH, and TP contents in liver tissues were significantly reinstated towards normalization by the ABEO. Histopathological study further confirmed these findings. In addition, ABEO showed mild antioxidant activity in 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and β-carotene-linoleic acid assays. PMID:27293452

  8. Chemical characterization by GC-MS and in vitro activity against Candida albicans of volatile fractions prepared from Artemisia dracunculus, Artemisia abrotanum, Artemisia absinthium and Artemisia vulgaris

    PubMed Central

    2014-01-01

    Background A large number of essential oils is reported to have significant activity against Candida albicans. But the different chemical composition influences the degree of their activity. The intention of this study was to investigate the chemical composition and the activity against Candida albicans of volatile oils obtained from Artemisia dracunculus, A. abrotanum, A. absinthium and A. vulgaris (Asteraceae). The aim of the study was to identify new chemical compounds that have effect against C. albicans. The essential oils were obtained by hydrodistillation or extraction with dichloromethane (a new procedure we developed trying to obtain better, more separated compounds) from air dried above ground plant material and analyzed by GC-MS. Additionally commercial essential oils from the same species were tested. The Candida albicans inhibition studies were carried out by the paper disc diffusion method. Results The essential oils shared common components but presented differences in composition and showed variable antifungal activity. Davanone and derivatives thereof, compounds with silphiperfolane skeleton, estragole, davanone oil, β-thujone, sabinyl acetate, herniarin, cis-chrysanthenyl acetate, 1,8-cineol, and terpineol were the main components of Artemisia volatiles. Conclusions Among the volatile fractions tested those from A. abrotanum containing davanone or silphiperfolane derivatives showed the highest antifungal activity. The in vitro tests revealed that the Artemisia oils are promising candidates for further research to develop novel anti-candida drugs. PMID:24475951

  9. Aroma active volatiles in four southern highbush blueberry cultivars determined by gas chromatography-olfactometry (GC-O) and gas chromatography-mass spectrometry (GC-MS).

    PubMed

    Du, Xiaofen; Rouseff, Russell

    2014-05-21

    Aroma active volatiles in four southern highbush blueberry cultivars ('Prima Dona', 'Jewel', 'Snow Chaser', and 'Kestrel') were determined using solid phase microextraction (SPME) in combination with gas chromatography-olfactometry (GC-O) and identified via GC-PFPD and GC-MS using retention indices of reference compounds and mass spectral data. The aromas of total, unseparated SPME extracts evaluated using GC-O were rated 8.2-9.0/10 for the four cultivars in terms of similarity to the original blueberry homogenates. In terms of GC-O aroma similarity, those aroma active volatile groups characterized as green, fruity, and floral were most intense. Of the 43 volatiles found to have aroma activity, 38 were identified and 13 had not been previously reported in blueberries. Although linalool and (E)-2-hexenal were common major aroma impact volatiles, dominant aroma-active volatiles were different for each cultivar. Principal component analysis confirmed that each cultivar possessed a unique aroma active profile as each cultivar was clustered into a separate score plot quadrant.

  10. Heterogeneity of Multiple Sclerosis Lesions in Multislice Myelin Water Imaging

    PubMed Central

    Faizy, Tobias Djamsched; Thaler, Christian; Kumar, Dushyant; Sedlacik, Jan; Broocks, Gabriel; Grosser, Malte; Stellmann, Jan-Patrick; Heesen, Christoph; Fiehler, Jens; Siemonsen, Susanne

    2016-01-01

    Purpose To assess neuroprotection and remyelination in Multiple Sclerosis (MS), we applied a more robust myelin water imaging (MWI) processing technique, including spatial priors into image reconstruction, which allows for lower SNR, less averages and shorter acquisition times. We sought to evaluate this technique in MS-patients and healthy controls (HC). Materials and Methods Seventeen MS-patients and 14 age-matched HCs received a 3T Magnetic Resonance Imaging (MRI) examination including MWI (8 slices, 12 minutes acquisition time), T2w and T1mprage pre and post gadolinium (GD) administration. Black holes (BH), contrast enhancing lesions (CEL) and T2 lesions were marked and registered to MWI. Additionally, regions of interest (ROI) were defined in the frontal, parietal and occipital normal appearing white matter (NAWM)/white matter (WM), the corticospinal tract (CST), the splenium (SCC) and genu (GCC) of the corpus callosum in patients and HCs. Mean values of myelin water fraction (MWF) were determined for each ROI. Results Significant differences (p≤0.05) of the MWF were found in all three different MS-lesion types (BH, CEL, T2 lesions), compared to the WM of HCs. The mean MWF values among the different lesion types were significantly differing from each other. Comparing MS-patients vs. HCs, we found a significant (p≤0.05) difference of the MWF in all measured ROIs except of GCC and SCC. The mean reduction of MWF in the NAWM of MS-patients compared to HCs was 37%. No age, sex, disability score and disease duration dependency was found for the NAWM MWF. Conclusion MWF measures were in line with previous studies and lesions were clearly visible in MWI. MWI allows for quantitative assessment of NAWM and lesions in MS, which could be used as an additional sensitive imaging endpoint for larger MS studies. Measurements of the MWF also differ between patients and healthy controls. PMID:26990645

  11. Chemical repair activity of free radical scavenger edaravone: reduction reactions with dGMP hydroxyl radical adducts and suppression of base lesions and AP sites on irradiated plasmid DNA.

    PubMed

    Hata, Kuniki; Urushibara, Ayumi; Yamashita, Shinichi; Lin, Mingzhang; Muroya, Yusa; Shikazono, Naoya; Yokoya, Akinari; Fu, Haiying; Katsumura, Yosuke

    2015-01-01

    Reactions of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) with deoxyguanosine monophosphate (dGMP) hydroxyl radical adducts were investigated by pulse radiolysis technique. Edaravone was found to reduce the dGMP hydroxyl radical adducts through electron transfer reactions. The rate constants of the reactions were greater than 4 × 10(8) dm(3) mol(-1) s(-1) and similar to those of the reactions of ascorbic acid, which is a representative antioxidant. Yields of single-strand breaks, base lesions, and abasic sites produced in pUC18 plasmid DNA by gamma ray irradiation in the presence of low concentrations (10-1000 μmol dm(-3)) of edaravone were also quantified, and the chemical repair activity of edaravone was estimated by a method recently developed by the authors. By comparing suppression efficiencies to the induction of each DNA lesion, it was found that base lesions and abasic sites were suppressed by the chemical repair activity of edaravone, although the suppression of single-strand breaks was not very effective. This phenomenon was attributed to the chemical repair activity of edaravone toward base lesions and abasic sites. However, the chemical repair activity of edaravone for base lesions was lower than that of ascorbic acid.

  12. Analysis of aroma-active compounds in three sweet osmanthus (Osmanthus fragrans) cultivars by GC-olfactometry and GC-MS*

    PubMed Central

    Cai, Xuan; Mai, Rong-zhang; Zou, Jing-jing; Zhang, Hong-yan; Zeng, Xiang-ling; Zheng, Ri-ru; Wang, Cai-yun

    2014-01-01

    Objective: Aroma is the core factor in aromatherapy. Sensory evaluation of aromas differed among three sweet osmanthus (Osmanthus fragrans) cultivar groups. The purpose of this study was to investigate the aroma-active compounds responsible for these differences. Methods: Gas chromatography-olfactometry (GC-O) and GC-mass spectrometry (GC-MS) were used to analyze the aroma-active compounds and volatiles of creamy-white (‘Houban Yingui’, HBYG), yellow (‘Liuye Jingui’, LYJG), and orange (‘Gecheng Dangui’, GCDG) cultivars. Results: Seventeen aroma-active compounds were detected among 54 volatiles. trans-β-Ocimene, trans-β-ionone, and linalool, which were major volatiles, were identified as aroma-active, while cis-3-hexenyl butanoate, γ-terpinene, and hexyl butanoate were also aroma-active compounds, although their contents were low. Analysis of the odors was based on the sum of the modified frequency (MF) values of aroma-active compounds in different odor groups. HBYG contained more herb odors, contributed by cis-β-ocimene and trans-β-ocimene, while LYJG had more woody/violet/fruity odors released by trans-β-ionone, α-ionone, and hexyl butanoate. In GCDG, the more floral odors were the result of cis-linalool oxide, trans-linalool oxide, and linalool. Conclusions: Aroma-active compounds were not necessarily only the major volatiles: some volatiles with low content also contributed to aroma. The aroma differences among the three cultivars resulted from variation in the content of different odor groups and in the intensities of aroma-active compounds. PMID:25001223

  13. Reduced cortisol levels in cerebrospinal fluid and differential distribution of 11beta-hydroxysteroid dehydrogenases in multiple sclerosis: implications for lesion pathogenesis.

    PubMed

    Heidbrink, Claudia; Häusler, Sebastian F M; Buttmann, Mathias; Ossadnik, Monika; Strik, Herwig M; Keller, Andreas; Buck, Dorothea; Verbraak, Evert; van Meurs, Marjan; Krockenberger, Mathias; Mehling, Matthias; Mittelbronn, Michel; Laman, Jon D; Wiendl, Heinz; Wischhusen, Jörg

    2010-08-01

    Relapses during multiple sclerosis (MS) are treated by administration of exogenous corticosteroids. However, little is known about the bioavailability of endogenous steroids in the central nervous system (CNS) of MS patients. We thus determined cortisol and dehydroepiandrosterone (DHEA) levels in serum and cerebrospinal fluid (CSF) samples from 34 MS patients, 28 patients with non-inflammatory neurological diseases (NIND) and 16 patients with other inflammatory neurological diseases (OIND). This revealed that MS patients - in sharp contrast to patients with OIND - show normal cortisol concentrations in serum and lowered cortisol levels in the CSF during acute relapses. This local cortisol deficit may relate to poor local activation of cortisone via 11beta-hydroxysteroid dehydrogenase type 1 (11bHSD1) or to inactivation via 11bHSD2. Accordingly, 11bHSD2 was found to be expressed within active plaques, whereas 11bHSD1 was predominantly detected in surrounding "foamy" macrophages. Our study thus provides new insights into the impaired endogenous CNS cortisol regulation in MS patients and its possible relation to MS lesion pathogenesis. Moreover, an observed upregulation of 11bHSD1 in myelin-loaded macrophages in vitro suggests an intriguing hypothesis for the self-limiting nature of MS lesion development. Finally, our findings provide an attractive explanation for the effectivity of high- vs. low-dose exogenous corticosteroids in the therapy of acute relapses.

  14. Isolation and identification of colourless caffeoyl compounds in purple sweet potato by HPLC-DAD-ESI/MS and their antioxidant activities.

    PubMed

    Zhao, Jin-Ge; Yan, Qian-Qian; Xue, Ren-Yu; Zhang, Jian; Zhang, Yu-Qing

    2014-10-15

    More than 10 red anthocyanins and related glucosides have been isolated and identified from purple sweet potato (Ipomoea batatas, Ayamurasaki) in the recent decades. This paper reports the isolation of colourless caffeoyl compounds from purple sweet potato using AB-8 macroresin absorption and semi-preparative HPLC-DAD. The structures of the five isolated monomers were identified as: 5-caffeoylquinic acid (1), 6-O-caffeoyl-β-d-fructofuranosyl-(2-1)-α-d-glucopyranoside (2) and trans-4,5-dicaffeoylquinic acid (3), 3,5-dicaffeoylquinic acid (4), 4,5-dicaffeoylquinic acid (5), and by ESI/MS and NMR. Compounds 1, 4 and 5 were reported previously in combination with anthocyanins in purple sweet potato, whereas 2 and 3 were found for the first time. In vitro antioxidant assay showed trans-4,5-dicaffeoylquinic acid has significant antioxidant activities. These results should lay the groundwork for further work identifying purple sweet potato as a healthy food.

  15. 18F-FDG PET/CT focal, but not osteolytic, lesions predict the progression of smoldering myeloma to active disease.

    PubMed

    Zamagni, E; Nanni, C; Gay, F; Pezzi, A; Patriarca, F; Bellò, M; Rambaldi, I; Tacchetti, P; Hillengass, J; Gamberi, B; Pantani, L; Magarotto, V; Versari, A; Offidani, M; Zannetti, B; Carobolante, F; Balma, M; Musto, P; Rensi, M; Mancuso, K; Dimitrakopoulou-Strauss, A; Chauviè, S; Rocchi, S; Fard, N; Marzocchi, G; Storto, G; Ghedini, P; Palumbo, A; Fanti, S; Cavo, M

    2016-02-01

    Identification of patient sub-groups with smoldering multiple myeloma (SMM) at high risk of progression to active disease (MM) is an important goal. 18F-FDG PET/CT (positron emission tomography (PET) integrated with computed tomography (PET/CT) using glucose labelled with the positron-emitting radionuclide (18)F) allows for assessing early skeletal involvement. Identification of osteolytic lesions by this technique has recently been incorporated into the updated International Myeloma Working Group criteria for MM diagnosis. However, no data are available regarding the impact of focal lesions (FLs) without underlying osteolysis on time to progression (TTP) to MM. We hence prospectively studied a cohort of 120 SMM patients with PET/CT. PET/CT was positive in 16% of patients (1 FL: 8, 2 FLs: 3, >3 FLs: 6, diffuse bone marrow involvement: 2). With a median follow-up of 2.2 years, 38% of patients progressed to MM, in a median time of 4 years, including 21% with skeletal involvement. The risk of progression of those with positive PET/CT was 3.00 (95% confidence interval 1.58-5.69, P=0.001), with a median TTP of 1.1 versus 4.5 years for PET/CT-negative patients. The probability of progression within 2 years was 58% for positive versus 33% for negative patients. In conclusion, PET/CT positivity significantly increased the risk of progression of SMM to MM. PET/CT could become a new tool to define high-risk SMM. PMID:26490489

  16. Ecdysteroids in Sida tuberculata R.E. Fries (Malvaceae): chemical composition by LC-ESI-MS and selective anti-Candida krusei activity.

    PubMed

    da Rosa, Hemerson Silva; de Camargo, Vanessa Brum; Camargo, Graziela; Garcia, Cássia V; Fuentefria, Alexandre M; Mendez, Andreas S L

    2015-09-01

    Sida tuberculata is found in a region of South America and has traditionally been consumed as an infusion or tea. The chemical composition and antifungal activity of aqueous infusions from leaves and roots were investigated. LC-ESI-MS mass spectra were successfully obtained and used to identify four ecdysteroids: 20-hydroxyecdysone-3-O-β-D-glycopyranoside, 20-hydroxyecdysone, 20-hydroxyecdysone-3-O-β-D-xylose and a hydroxyecdysterone derivative. The in vitro antifungal activity was studied, and the minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) were established against Candida krusei isolates. The antibiofilm activity was evaluated by the determination of the biofilm removal efficiency in contaminated central venous catheter (CVC) coupons. The preparations exhibited antifungal activity against the species tested, with MICs ranging from 3.90 to 62.50 μg/ml. The infusion removed the C. krusei biofilm after 90 min of exposure. The observed bioactivity and composition of ecdysteroids will contribute to the future development of antifungal substances for clinical use or as food additives. PMID:25842327

  17. Assessment of antimicrobial and antiprotozoal activity of the olive oil macerate samples of Hypericum perforatum and their LC-DAD-MS analyses.

    PubMed

    Orhan, Ilkay Erdogan; Kartal, Murat; Gülpinar, Ali Rifat; Cos, Paul; Matheeussen, An; Maes, Louis; Tasdemir, Deniz

    2013-06-01

    Twenty-one samples of traditionally-prepared (home-made) and ready-made (commercial) St. John's Wort olive oil macerates were profiled for their in vitro antimicrobial and antiprotozoal activity. Their cytotoxic potential was evaluated on MRC-5 fibroblasts. In the antiprotozoal assays, ten of the oils inhibited Trypanosoma brucei rhodesiense (IC(50) 15.9-64.5 μg/mL), while only one oil exerted antimicrobial activity towards Staphylococcus aureus (IC(50)=88.7 μg/mL). LC-DAD-MS data revealed the presence of pseudohypericin (0.135-3.280 μg/g) and hypericin (0.277-6.634 μg/g) in all the oils, whereas chlorogenic acid (1.063 μg/g) was detected only in one oil sample. Hyperforin was detected in four (0.977-2.399 μg/g) and adhyperforin in six samples (0.005-3.165 μg/g). Hypericin and pseudohypericin were common in the active oils, whereas hyperforin, adhyperforin, and chlorogenic acid were absent in these samples. Our results indicated that if the correct plant material is used, the infused oils from Hypericum perforatum may contain active components.

  18. Ecdysteroids in Sida tuberculata R.E. Fries (Malvaceae): chemical composition by LC-ESI-MS and selective anti-Candida krusei activity.

    PubMed

    da Rosa, Hemerson Silva; de Camargo, Vanessa Brum; Camargo, Graziela; Garcia, Cássia V; Fuentefria, Alexandre M; Mendez, Andreas S L

    2015-09-01

    Sida tuberculata is found in a region of South America and has traditionally been consumed as an infusion or tea. The chemical composition and antifungal activity of aqueous infusions from leaves and roots were investigated. LC-ESI-MS mass spectra were successfully obtained and used to identify four ecdysteroids: 20-hydroxyecdysone-3-O-β-D-glycopyranoside, 20-hydroxyecdysone, 20-hydroxyecdysone-3-O-β-D-xylose and a hydroxyecdysterone derivative. The in vitro antifungal activity was studied, and the minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) were established against Candida krusei isolates. The antibiofilm activity was evaluated by the determination of the biofilm removal efficiency in contaminated central venous catheter (CVC) coupons. The preparations exhibited antifungal activity against the species tested, with MICs ranging from 3.90 to 62.50 μg/ml. The infusion removed the C. krusei biofilm after 90 min of exposure. The observed bioactivity and composition of ecdysteroids will contribute to the future development of antifungal substances for clinical use or as food additives.

  19. New findings on the in vivo antioxidant activity of Curcuma longa extract by an integrated (1)H NMR and HPLC-MS metabolomic approach.

    PubMed

    Dall'Acqua, Stefano; Stocchero, Matteo; Boschiero, Irene; Schiavon, Mariano; Golob, Samuel; Uddin, Jalal; Voinovich, Dario; Mammi, Stefano; Schievano, Elisabetta

    2016-03-01

    Curcuminoids possess powerful antioxidant activity as demonstrated in many chemical in vitro tests and in several in vivo trials. Nevertheless, the mechanism of this activity is not completely elucidated and studies on the in vivo antioxidant effects are still needed. Metabolomics may be used as an attractive approach for such studies and in this paper, we describe the effects of oral administration of a Curcuma longa L. extract (150 mg/kg of total curcuminoids) to 12 healthy rats with particular attention to urinary markers of oxidative stress. The experiment was carried out over 33 days and changes in the 24-h urine samples metabolome were evaluated by (1)H NMR and HPLC-MS. Both techniques produced similar representations for the collected samples confirming our previous study. Modifications of the urinary metabolome lead to the observation of different variables proving the complementarity of (1)H NMR and HPLC-MS for metabolomic purposes. The urinary levels of allantoin, m-tyrosine, 8-hydroxy-2'-deoxyguanosine, and nitrotyrosine were decreased in the treated group thus supporting an in vivo antioxidant effect of the oral administration of Curcuma extract to healthy rats. On the other hand, urinary TMAO levels were higher in the treated compared to the control group suggesting a role of curcumin supplementation on microbiota or on TMAO urinary excretion. Furthermore, the urinary levels of the sulphur containing compounds taurine and cystine were also changed suggesting a role for such constituents in the biochemical pathways involved in Curcuma extract bioactivity and indicating the need for further investigation on the complex role of antioxidant curcumin effects. PMID:26712080

  20. New findings on the in vivo antioxidant activity of Curcuma longa extract by an integrated (1)H NMR and HPLC-MS metabolomic approach.

    PubMed

    Dall'Acqua, Stefano; Stocchero, Matteo; Boschiero, Irene; Schiavon, Mariano; Golob, Samuel; Uddin, Jalal; Voinovich, Dario; Mammi, Stefano; Schievano, Elisabetta

    2016-03-01

    Curcuminoids possess powerful antioxidant activity as demonstrated in many chemical in vitro tests and in several in vivo trials. Nevertheless, the mechanism of this activity is not completely elucidated and studies on the in vivo antioxidant effects are still needed. Metabolomics may be used as an attractive approach for such studies and in this paper, we describe the effects of oral administration of a Curcuma longa L. extract (150 mg/kg of total curcuminoids) to 12 healthy rats with particular attention to urinary markers of oxidative stress. The experiment was carried out over 33 days and changes in the 24-h urine samples metabolome were evaluated by (1)H NMR and HPLC-MS. Both techniques produced similar representations for the collected samples confirming our previous study. Modifications of the urinary metabolome lead to the observation of different variables proving the complementarity of (1)H NMR and HPLC-MS for metabolomic purposes. The urinary levels of allantoin, m-tyrosine, 8-hydroxy-2'-deoxyguanosine, and nitrotyrosine were decreased in the treated group thus supporting an in vivo antioxidant effect of the oral administration of Curcuma extract to healthy rats. On the other hand, urinary TMAO levels were higher in the treated compared to the control group suggesting a role of curcumin supplementation on microbiota or on TMAO urinary excretion. Furthermore, the urinary levels of the sulphur containing compounds taurine and cystine were also changed suggesting a role for such constituents in the biochemical pathways involved in Curcuma extract bioactivity and indicating the need for further investigation on the complex role of antioxidant curcumin effects.

  1. GC-MS analysis of bioactive components and biosynthesis of silver nanoparticles using Hybanthus enneaspermus at room temperature evaluation of their stability and its larvicidal activity.

    PubMed

    Suman, T Y; Rajasree, S R Radhika; Jayaseelan, C; Mary, R Regina; Gayathri, S; Aranganathan, L; Remya, R R

    2016-02-01

    Green synthesis of silver nanoparticles (AgNPs) using Hybanthus enneaspermus extract at room temperature that act as a reducing agent as well as capping agent has been investigated. The synthesized AgNPs were characterized by UV-visible spectroscopy, X-ray diffraction (XRD), Fourier transform infrared (FTIR), zeta potential, and dynamic light scattering (DLS) transmission electron microscopy (TEM) and energy-dispersive X-ray (EDX). The silver surface plasmon resonance was observed at 420 nm in the UV-visible spectrum. XRD peaks were observed at 2θ values in 38.20°, 44.40°, 64.60°, and 77.50° which are indexed as (111), (200), (220), and (311) bands of face-centered cubic (fcc) structures of silver. FTIR revealed the AgNPs were capped with plant compounds of alcohol, phenols, carbonyl, amines, and amide functional groups. TEM image shows that the particles were of spherical, hexagonal, and triangular in shape, and the size range was 16-26 nm. Further, DLS exhibits the average size of 25.2 nm and the zeta values were measured (-27.1 mV) which proves the stability of the AgNPs. The conversion of Ag(+) ions into Ag(0) was calculated using inductively coupled plasma atomic emission spectroscopy (ICP-MS) and was found to be 96 %. The biosynthesized AgNPs showed the larvicidal activity with the LC50 values of 17.24 and 13.12 mg/L against the fourth-instar larvae of Anopheles subpictus and Culex quinquefasciatus, respectively. The GC-MS analysis of the plant extract showed that 39 bioactive phytochemical compounds have been found to possess a wide range of activities, which may help in the protection against incurable diseases.

  2. Benign breast lesions: Ultrasound

    PubMed Central

    Masciadri, N.; Ferranti, C.

    2011-01-01

    Benign breast diseases constitute a heterogeneous group of lesions arising in the mammary epithelium or in other mammary tissues, and they may also be linked to vascular, inflammatory or traumatic pathologies. Most lesions found in women consulting a physician are benign. Ultrasound (US) diagnostic criteria indicating a benign lesion are described as well as US findings in the most frequent benign breast lesions. PMID:23396888

  3. The Small Breathing Amplitude at the Upper Lobes Favors the Attraction of Polymorphonuclear Neutrophils to Mycobacterium tuberculosis Lesions and Helps to Understand the Evolution toward Active Disease in An Individual-Based Model

    PubMed Central

    Cardona, Pere-Joan; Prats, Clara

    2016-01-01

    Infection with Mycobacterium tuberculosis (Mtb) can induce two kinds of lesions, namely proliferative and exudative. The former are based on the presence of macrophages with controlled induction of intragranulomatous necrosis, and are even able to stop its physical progression, thus avoiding the induction of active tuberculosis (TB). In contrast, the most significant characteristic of exudative lesions is their massive infiltration with polymorphonuclear neutrophils (PMNs), which favor enlargement of the lesions and extracellular growth of the bacilli. We have built an individual-based model (IBM) (known as “TBPATCH”) using the NetLogo interface to better understand the progression from Mtb infection to TB. We have tested four main factors previously identified as being able to favor the infiltration of Mtb-infected lesions with PMNs, namely the tolerability of infected macrophages to the bacillary load; the capacity to modulate the Th17 response; the breathing amplitude (BAM) (large or small in the lower and upper lobes respectively), which influences bacillary drainage at the alveoli; and the encapsulation of Mtb-infected lesions by the interlobular septae that structure the pulmonary parenchyma into secondary lobes. Overall, although all the factors analyzed play some role, the small BAM is the major factor determining whether Mtb-infected lesions become exudative, and thus induce TB, thereby helping to understand why this usually takes place in the upper lobes. This information will be very useful for the design of future prophylactic and therapeutic approaches against TB. PMID:27065951

  4. Optimization of HS-GC-FID-MS Method for Residual Solvent Profiling in Active Pharmaceutical Ingredients Using DoE.

    PubMed

    Poceva Panovska, Ana; Acevska, Jelena; Stefkov, Gjoshe; Brezovska, Katerina; Petkovska, Rumenka; Dimitrovska, Aneta

    2016-02-01

    Within this research, a headspace (HS) gas chromatography-flame ionization detector-mass spectrometry method was developed for profiling of residual solvents (RSs) in active pharmaceutical ingredients (APIs). Design of experiment was used for optimization of sample preparation, as well as for robustness testing of the method. HS equilibration temperature and dilution medium were detected as parameters with greater impact on the sensitivity, compared with the time used for equilibration of the samples. Regardless of the sample solubility, the use of water for sample preparation was found to be crucial for better sensitivity. The use of a well-designed strategy for method development and robustness testing, additional level of identification confidence, as well as use of internal standard provided a strong and reliable analytical tool for API fingerprinting, thus enabling the authentication of the substance based on the RS profile. PMID:26290585

  5. Controlling hydrogen scrambling in multiply charged protein ions during collisional activation: implications for top-down hydrogen/deuterium exchange MS utilizing collisional activation in the gas phase.

    PubMed

    Abzalimov, Rinat R; Kaltashov, Igor A

    2010-02-01

    Hydrogen exchange in solution combined with ion fragmentation in the gas phase followed by MS detection emerged in recent years as a powerful tool to study higher order protein structure and dynamics. However, a certain type of ion chemistry in the gas phase, namely, internal rearrangement of labile hydrogen atoms (the so-called hydrogen scrambling), is often cited as a factor limiting the utility of this experimental technique. Although several studies have been carried out to elucidate the roles played by various factors in the occurrence and the extent of hydrogen scrambling, there is still no consensus as to what experimental protocol should be followed to avoid or minimize it. In this study we employ fragmentation of mass-selected subpopulations of protein ions to assess the extent of internal proton mobility prior to dissociation. A unique advantage of tandem MS is that it not only provides a means to map the deuterium content of protein ions whose overall levels of isotope incorporation can be precisely defined by controlling the mass selection window, but also correlates this spatial isotope distribution with such global characteristic as the protein ion charge state. Hydrogen scrambling does not occur when the charge state of the precursor protein ions selected for fragmentation is high. Fragment ions derived from both N- and C-terminal parts of the protein are equally unaffected by scrambling. However, spatial distribution of deuterium atoms obtained by fragmenting low-charge-density protein ions is consistent with a very high degree of scrambling prior to the dissociation events. The extent of hydrogen scrambling is also high when multistage fragmentation is used to probe deuterium incorporation locally. Taken together, the experimental results provide a coherent picture of intramolecular processes occurring prior to the dissociation event and provide guidance for the design of experiments whose outcome is unaffected by hydrogen scrambling.

  6. The effects on auditory neurocognitive evoked responses and contingent negative variation activity of frontal cortex lesions or ablations in man: three new case studies.

    PubMed

    Zappoli, R; Versari, A; Zappoli, F; Chiaramonti, R; Zappoli Thyrion, G D; Grazia Arneodo, M; Zerauschek, V

    2000-11-01

    Our previous research in patients with extensive surgical ablations of the prefrontal cortex contradict the hypothesis of some authors that the generators of several auditory event-related potentials (ERPs) (N100; P200; N200; P300; SW), recordable in humans with depth/scalp electrodes and MEG over the prefrontal dorsolateral cortical areas, are essentially located in medial prefrontal and anterior cingulate-limbic cortices. Using a standard CNV paradigm, 21 EEG electrodes and topographic mapping analysis, the post-warning (S1) auditory N100a b c, P200, P300 (binaural clicks) and CNV activity were recorded in three additional patients after extensive dorsolateral and/or medial prefrontal cortex ablations, verified through CT/MRI examinations. No true post-S1/CNV components were recordable over the ablated frontal areas, only sporadic volume-conducted ERPs probably generated in the temporo-parietal lobes or posterior cingulate gyrus. For one of these patients, after excision of a vast right frontal epileptogenic cortical region (including extensive dorsolateral areas, but sparing the fronto-medial cortex and anterior/middle cingulate gyrus), no post-S1/CNV components were recordable over the ablated regions. These latest observations again indicate that independent neuronal generators of several post-S1 auditory and CNV components are located in the dorsolateral supramodal premotor/prefrontal cortical areas which are directly, ipsilaterally connected to the uni/multimodal temporo-parieto-occipital sensory and associative regions through the long, two-way, fairly superficial, superior arcuate-longitudinal and deeper superior and inferior occipito-frontal bundles. Clear and almost constant differences in the latency of some post-S1 N100 subcomponents (especially the time-lapses between onset and the highest amplitude of the N100 a and c) over various posterior, central and anterior cortical areas sequentially involved, roughly measured in 10 normal subjects along the

  7. [Improvement in spontaneous and acquired spatial behaviors following lesions of septal dopaminergic afferents in mice: possible relations with hippocampal cholinergic activity].

    PubMed

    Galey, D; Durkin, T; Sifakis, G; Jaffard, R

    1984-01-01

    Recent evidence from pharmacological studies support the view that dopaminergic afferents to the septal complex which originate from the mesencephalic A10 area, exert a tonic inhibitory control over the activity of the septal-hippocampal cholinergic neurons. Accordingly one could predict that the release from such an inhibition by lesion of the septal dopaminergic terminals might improve performance in tasks known to be related to hippocampal cholinergic activity. In order to test this hypothesis mice of the C57BL/6 strain received a bilateral injection of 6-hydroxydopamine in the lateral septal nucleus; they were compared to subjects receiving saline and to unoperated control mice in tests performed in a T-maze: spontaneous alternation, acquisition and reversal of spatial discrimination. In all tasks, performance of experimental subjects was improved relative to controls. However, subsequent experiments showed that this improvement was not observed when visual (light/dark) discrimination was used. Finally, 6-hydroxydopamine injected mice exhibited a substantial increase in hippocampal sodium-dependent high affinity choline uptake (+ 16.7%). These results are discussed in relation to the three main theories concerning the role of the septo-hippocampal complex and cholinergic system in the control of behavior (i.e. Pavlovian internal inhibition, spatial mapping and working memory). Only the theory of spatial cognition seems to account for our present findings.

  8. Comparison of Aroma-Active Volatiles in Oolong Tea Infusions Using GC-Olfactometry, GC-FPD, and GC-MS.

    PubMed

    Zhu, JianCai; Chen, Feng; Wang, LingYing; Niu, YunWei; Yu, Dan; Shu, Chang; Chen, HeXing; Wang, HongLin; Xiao, ZuoBing

    2015-09-01

    The aroma profile of oolong tea infusions (Dongdingwulong, DDWL; Tieguanyin, TGY; Dahongpao, DHP) were investigated in this study. Gas chromatography-olfactometry (GC-O) with the method of aroma intensity (AI) was employed to investigate the aroma-active compounds in tea infusions. The results presented forty-three, forty-five, and forty-eight aroma-active compounds in the TGY, DHP, and DDWL infusions, including six, seven, and five sulfur compounds, respectively. In addition, the concentration of volatile compounds in the tea infusions was further quantitated by solid phase microextraction-gas chromatography (SPME)-GC-MS and SPME-GC-flame photometric detection (FPD). Totally, seventy-six and thirteen volatile and sulfur compounds were detected in three types of tea infusions, respectively. Quantitative results showed that forty-seven aroma compounds were at concentrations higher than their corresponding odor thresholds. On the basis of the odor activity values (OAVs), 2-methylpropanal (OAV: 230-455), 3-methylbutanal (1-353), 2-methylbutanal (34-68), nerolidol (108-184), (E)-2-heptenal (148-294), hexanal (134-230), octanal (28-131), β-damascenone (29-59), indole (96-138), 6-methyl-5-hepten-2-one (34-67), (R)-(-)-linalool (63-87), and dimethyl sulfide (7-1320) presented relatively higher OAVs than those of other compounds, indicating the importance of these compounds in the overall aroma of tea infusions.

  9. Pine Bark and Green Tea Concentrated Extracts: Antioxidant Activity and Comprehensive Characterization of Bioactive Compounds by HPLC–ESI-QTOF-MS

    PubMed Central

    Cádiz-Gurrea, María de la Luz; Fernández-Arroyo, Salvador; Segura-Carretero, Antonio

    2014-01-01

    The consumption of polyphenols has frequently been associated with low incidence of degenerative diseases. Most of these natural antioxidants come from fruits, vegetables, spices, grains and herbs. For this reason, there has been increasing interest in identifying plant extract compounds. Polymeric tannins and monomeric flavonoids, such as catechin and epicatechin, in pine bark and green tea extracts could be responsible for the higher antioxidant activities of these extracts. The aim of the present study was to characterize the phenolic compounds in pine bark and green tea concentrated extracts using high-performance liquid chromatography coupled to electrospray ionization mass spectrometry (HPLC–ESI-QTOF-MS). A total of 37 and 35 compounds from pine bark and green tea extracts, respectively, were identified as belonging to various structural classes, mainly flavan-3-ol and its derivatives (including procyanidins). The antioxidant capacity of both extracts was evaluated by three complementary antioxidant activity methods: Trolox equivalent antioxidant capacity (TEAC), ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC). Higher antioxidant activity values by each method were obtained. In addition, total polyphenol and flavan-3-ol contents, which were determined by Folin–Ciocalteu and vanillin assays, respectively, exhibited higher amounts of gallic acid and (+)-catechin equivalents. PMID:25383680

  10. The chiral herbicide beflubutamid (I): Isolation of pure enantiomers by HPLC, herbicidal activity of enantiomers, and analysis by enantioselective GC-MS.

    PubMed

    Buerge, Ignaz J; Bächli, Astrid; De Joffrey, Jean-Pierre; Müller, Markus D; Spycher, Simon; Poiger, Thomas

    2013-07-01

    For many chiral pesticides, little information is available on the properties and fate of individual stereoisomers. A basic data set would, first of all, include stereoisomer-specific analytical methods and data on the biological activity of stereoisomers. The herbicide beflubutamid, which acts as an inhibitor of carotenoid biosynthesis, is currently marketed as racemate against dicotyledonous weeds in cereals. Here, we present analytical methods for enantiomer separation of beflubutamid and two metabolites based on chiral HPLC. These methods were used to assign the optical rotation and to prepare milligram quantities of the pure enantiomers for further characterization with respect to herbicidal activity. In addition, sensitive analytical methods were developed for enantiomer separation and quantification of beflubutamid and its metabolites at trace level, using chiral GC-MS. In miniaturized biotests with garden cress, (-)-beflubutamid showed at least 1000× higher herbicidal activity (EC50, 0.50 μM) than (+)-beflubutamid, as determined by analysis of chlorophyll a in 5-day-old leaves. The agricultural use of enantiopure (-)-beflubutamid rather than the racemic compound may therefore be advantageous from an environmental perspective. In further biotests, the (+)-enantiomer of the phenoxybutanoic acid metabolite showed effects on root growth, possibly via an auxin-type mode of action, but at 100× higher concentrations than the structurally related herbicide (+)-mecoprop. PMID:22849576

  11. Comparison of Aroma-Active Volatiles in Oolong Tea Infusions Using GC-Olfactometry, GC-FPD, and GC-MS.

    PubMed

    Zhu, JianCai; Chen, Feng; Wang, LingYing; Niu, YunWei; Yu, Dan; Shu, Chang; Chen, HeXing; Wang, HongLin; Xiao, ZuoBing

    2015-09-01

    The aroma profile of oolong tea infusions (Dongdingwulong, DDWL; Tieguanyin, TGY; Dahongpao, DHP) were investigated in this study. Gas chromatography-olfactometry (GC-O) with the method of aroma intensity (AI) was employed to investigate the aroma-active compounds in tea infusions. The results presented forty-three, forty-five, and forty-eight aroma-active compounds in the TGY, DHP, and DDWL infusions, including six, seven, and five sulfur compounds, respectively. In addition, the concentration of volatile compounds in the tea infusions was further quantitated by solid phase microextraction-gas chromatography (SPME)-GC-MS and SPME-GC-flame photometric detection (FPD). Totally, seventy-six and thirteen volatile and sulfur compounds were detected in three types of tea infusions, respectively. Quantitative results showed that forty-seven aroma compounds were at concentrations higher than their corresponding odor thresholds. On the basis of the odor activity values (OAVs), 2-methylpropanal (OAV: 230-455), 3-methylbutanal (1-353), 2-methylbutanal (34-68), nerolidol (108-184), (E)-2-heptenal (148-294), hexanal (134-230), octanal (28-131), β-damascenone (29-59), indole (96-138), 6-methyl-5-hepten-2-one (34-67), (R)-(-)-linalool (63-87), and dimethyl sulfide (7-1320) presented relatively higher OAVs than those of other compounds, indicating the importance of these compounds in the overall aroma of tea infusions. PMID:26257073

  12. GC-MS characterisation and antibacterial activity evaluation of Nigella sativa oil against diverse strains of Salmonella.

    PubMed

    Sarwar, Arslan; Latif, Zakia

    2015-01-01

    Salmonella resistance is becoming a worldwide serious health issue in these days; therefore, it is an urgent need to develop some alternative approaches to overcome this problem. Twenty bacterial strains were isolated and purified from different environmental sources and confirmed as Salmonella by morphological and biochemical analyses. Further confirmation was done by 16s rRNA sequencing. Antibiotic susceptibility test was performed by well diffusion assay against different concentrations of Ceftriaxone and Ciprofloxacin. The behaviour of both antibiotics was different against diverse strains of Salmonella. Salmonella strains resistant to both antibiotics were analysed for antibacterial activity of natural extracts of Nigella sativa (black seeds). N. sativa oil was found to be more effective against Salmonella species for which even Ceftriaxone and Ciprofloxacin were ineffective. Gas chromatography and mass spectrometry analysis of N. sativa oil was also accomplished, exhibiting 10 compounds including thymoquinone, p-cymene, cis-carveol, thymol, α-phellandrene, α-pinene, β-pinene, trans-anethole, α-longipinene and longifolene.

  13. GC-MS characterisation and antibacterial activity evaluation of Nigella sativa oil against diverse strains of Salmonella.

    PubMed

    Sarwar, Arslan; Latif, Zakia

    2015-01-01

    Salmonella resistance is becoming a worldwide serious health issue in these days; therefore, it is an urgent need to develop some alternative approaches to overcome this problem. Twenty bacterial strains were isolated and purified from different environmental sources and confirmed as Salmonella by morphological and biochemical analyses. Further confirmation was done by 16s rRNA sequencing. Antibiotic susceptibility test was performed by well diffusion assay against different concentrations of Ceftriaxone and Ciprofloxacin. The behaviour of both antibiotics was different against diverse strains of Salmonella. Salmonella strains resistant to both antibiotics were analysed for antibacterial activity of natural extracts of Nigella sativa (black seeds). N. sativa oil was found to be more effective against Salmonella species for which even Ceftriaxone and Ciprofloxacin were ineffective. Gas chromatography and mass spectrometry analysis of N. sativa oil was also accomplished, exhibiting 10 compounds including thymoquinone, p-cymene, cis-carveol, thymol, α-phellandrene, α-pinene, β-pinene, trans-anethole, α-longipinene and longifolene. PMID:25147934

  14. Increased expression of p38 mitogen-activated protein kinase is related to the acute renal lesions induced by gentamicin.

    PubMed

    Volpini, R A; Balbi, A P C; Costa, R S; Coimbra, T M

    2006-06-01

    Mitogen-activated protein kinases (MAPK) may be involved in the pathogenesis of acute renal failure. This study investigated the expression of p-p38 MAPK and nuclear factor kappa B (NF-kappaB) in the renal cortex of rats treated with gentamicin. Twenty rats were injected with gentamicin, 40 mg/kg, i.m., twice a day for 9 days, 20 with gentamicin + pyrrolidine dithiocarbamate (PDTC, an NF-kappaB inhibitor), 14 with 0.15 M NaCl, i.m., twice a day for 9 days, and 14 with 0.15 M NaCl , i.m., twice a day for 9 days and PDTC, 50 mg kg(-1) day(-1), i.p., twice a day for 15 days. The animals were killed 5 and 30 days after the last of the injections and the kidneys were removed for histological, immunohistochemical and Western blot analysis and for nitrate determination. The results of the immunohistochemical study were evaluated by counting the p-p38 MAPK-positive cells per area of renal cortex measuring 0.05 mm2. Creatinine was measured by the Jaffé method in blood samples collected 5 and 30 days after the end of the treatments. Gentamicin-treated rats presented a transitory increase in plasma creatinine levels. In addition, animals killed 5 days after the end of gentamicin treatment presented acute tubular necrosis and increased nitrate levels in the renal cortex. Increased expression of p-p38 MAPK and NF-kappaB was also observed in the kidneys from these animals. The animals killed 30 days after gentamicin treatment showed residual areas of interstitial fibrosis in the renal cortex, although the expression of p-p38 MAPK in their kidneys did not differ from control. Treatment with PDTC reduced the functional and structural changes induced by gentamicin as well as the expression of p-p38 MAPK and NF-kappaB. The increased expression of p-p38 MAPK and NF-kappaB observed in these rats suggests that these signaling molecules may be involved in the pathogenesis of tubulointerstitial nephritis induced by gentamicin.

  15. Natalizumab plus interferon beta-1a reduces lesion formation in relapsing multiple sclerosis.

    PubMed

    Radue, Ernst-Wilhelm; Stuart, William H; Calabresi, Peter A; Confavreux, Christian; Galetta, Steven L; Rudick, Richard A; Lublin, Fred D; Weinstock-Guttman, Bianca; Wynn, Daniel R; Fisher, Elizabeth; Papadopoulou, Athina; Lynn, Frances; Panzara, Michael A; Sandrock, Alfred W

    2010-05-15

    The SENTINEL study showed that the addition of natalizumab improved outcomes for patients with relapsing multiple sclerosis (MS) who had experienced disease activity while receiving interferon beta-1a (IFNbeta-1a) alone. Previously unreported secondary and tertiary magnetic resonance imaging (MRI) measures are presented here. Patients received natalizumab 300 mg (n=589) or placebo (n=582) intravenously every 4 weeks plus IFNbeta-1a 30 microg intramuscularly once weekly. Annual MRI scans allowed comparison of a range of MRI end points versus baseline. Over 2 years, 67% of patients receiving natalizumab plus IFNbeta-1a remained free of new or enlarging T2-lesions compared with 30% of patients receiving IFNbeta-1a alone. The mean change from baseline in T2 lesion volume over 2 years decreased in patients receiving natalizumab plus IFNbeta-1a and increased in those receiving IFNbeta-1a alone (-277.5mm(3) versus 525.6mm(3); p<0.001). Compared with IFNbeta-1a alone, add-on natalizumab therapy resulted in a smaller increase in mean T1-hypointense lesion volume after 2 years (1821.3mm(3) versus 2210.5mm(3); p<0.001), a smaller mean number of new T1-hypointense lesions over 2 years (2.3 versus 4.1; p<0.001), and a slower rate of brain atrophy during the second year of therapy (-0.31% versus -0.40%; p=0.020). Natalizumab add-on therapy reduced gadolinium-enhancing, T1-hypointense, and T2 MRI lesion activity and slowed brain atrophy progression in patients with relapsing MS who experienced disease activity despite treatment with IFNbeta-1a alone. PMID:20236661

  16. The Charcot Lecture | Beating MS: A story of B cells, with twists and turns

    PubMed Central

    Hauser, Stephen L

    2015-01-01

    Autoimmune B cells play a major role in mediating tissue damage in multiple sclerosis (MS). In MS, B cells are believed to cross the blood-brain barrier and undergo stimulation, antigen-driven affinity maturation and clonal expansion within the supportive CNS environment. These highly restricted populations of clonally expanded B cells and plasma cells can be detected in MS lesions, in cerebrospinal fluid, and also in peripheral blood. In phase II trials in relapsing MS, monoclonal antibodies that target circulating CD20-positive B lymphocytes dramatically reduced disease activity. These beneficial effects occurred within weeks of treatment, indicating that a direct effect on B cells—and likely not on putative autoantibodies—was responsible. The discovery that depletion of B cells has an impact on MS biology enabled a paradigm shift in understanding how the inflammatory phase of MS develops, and will hopefully lead to development of increasingly selective therapies against culprit B cells and related humoral immune system pathways. More broadly, these studies illustrate how lessons learned from the bedside have unique power to inform translational research. They highlight the essential role of clinician scientists, currently endangered, who navigate the rocky and often unpredictable terrain between the worlds of clinical medicine and biomedical research. PMID:25480864

  17. Smoking is associated with increased lesion volumes and brain atrophy in multiple sclerosis

    PubMed Central

    Zivadinov, R; Weinstock-Guttman, B; Hashmi, K; Abdelrahman, N; Stosic, M; Dwyer, M; Hussein, S; Durfee, J; Ramanathan, M

    2009-01-01

    Background: Cigarette smoking has been linked to higher susceptibility and increased risk of progressive multiple sclerosis (MS). The effects of smoking on MRI characteristics of patients with MS have not been evaluated. Objectives: To compare the MRI characteristics in cigarette smoker and nonsmoker patients with MS. Methods: We studied 368 consecutive patients with MS (age 44.0 ±SD 10.2 years, disease duration 12.1 ± 9.1 years) comprising 240 never-smokers and 128 (34.8%) ever-smokers (currently active and former smokers). The average number of packs per day smoked (±SD) was 0.95 ± 0.65, and the mean duration of smoking was 18.0 ± 9.5 years. All patients obtained full clinical and quantitative MRI evaluation. MRI measures included T1, T2, and gadolinium contrast-enhancing (CE) lesion volumes (LVs) and measures of central, global, and tissue-specific brain atrophy. The associations between smoking status and MRI measurements were assessed in regression analysis. Results: Smoking was associated with increased Expanded Disability Status Scale (EDSS) scores (p = 0.004). The median EDSS scores (interquartile range) in the ever-smoker group and the active-smoker group were both 3.0 (2.0), compared with 2.5 (2.5) in never-smokers. There were adverse associations between smoking and the lesion measures including increased number of CE lesions (p < 0.001), T2 LV (p = 0.009), and T1 LV (p = 0.003). Smoking was associated with decreased brain parenchymal fraction (p = 0.047) and with increases in the lateral ventricle volume (p = 0.001) and third ventricle width (p = 0.023). Conclusions: Smoking is associated with increased blood–brain barrier disruption, higher lesion volumes, and greater atrophy in multiple sclerosis. GLOSSARY BPF = brain parenchymal fraction; CE = contrast-enhancing; CIS = clinically isolated syndromes; EDSS = Expanded Disability Status Scale; GMF = gray matter fraction; LV = lesion volume; LVV = lateral ventricle volume; MS = multiple sclerosis

  18. Acute cysticercosis favours rapid and more severe lesions caused by Leishmania major and Leishmania mexicana infection, a role for alternatively activated macrophages.

    PubMed

    Rodríguez-Sosa, Miriam; Rivera-Montoya, Irma; Espinoza, Arlett; Romero-Grijalva, Miriam; López-Flores, Roberto; González, Jorge; Terrazas, Luis I

    2006-08-01

    Parasitic helminths have developed complex mechanisms to modulate host immunity. In the present study we found that previous infection of mice with the cestode Taenia crassiceps favours parasitemia and induces larger cutaneous lesions during both Leishmania major and Leishmania mexicana co-infections. Analysis of cytokine responses into draining lymph nodes indicated that co-infection of T. crassiceps-Leishmania did not inhibit IFN-gamma production in response to Leishmania antigens, but significantly increased IL-4 production. Additionally, anti-Leishmania-specific IgG1 antibodies and total IgE increased in co-infected mice, whereas, IgG2a titers remained similar. Macrophages from Taenia-infected mice displayed increased mRNA transcripts of arginase-1, Ym1, and Mannose Receptor, as well as greater production of urea (all markers for an alternate activation state) compared to macrophages from Leishmania-infected mice. In contrast, lower mRNA transcripts for IL-12p35, IL-12p40, IL-23p19, and iNOS were detected in macrophages obtained from cestode-infected mice compared to uninfected and Leishmania-infected mice after LPS stimulation. The presence of cestode also generated impaired macrophage anti-leishmanicidal activity in vitro, as evidenced by the inability of these macrophages to prevent Leishmania growth compared to macrophages from uninfected mice. This was observed despite the fact that both groups of cells were exposed to IFN-gamma. Flow cytometry showed high IFN-gammaR expression on Taenia-induced macrophages. Thus, lack of response to IFN-gamma is not associated with the absence of its receptor. Our data suggest that cestode infection may favour Leishmania installation by inducing alternatively activated macrophages rather than inhibiting Th1-type responses.

  19. Neonatal Amygdala Lesions Lead to Increased Activity of Brain CRF Systems and Hypothalamic-Pituitary-Adrenal Axis of Juvenile Rhesus Monkeys

    PubMed Central

    Stephens, Shannon B.Z.; Henry, Amy; Villarreal, Trina; Bachevalier, Jocelyne; Wallen, Kim; Sanchez, Mar M.

    2014-01-01

    The current study examined the long-term effects of neonatal amygdala (Neo-A) lesions on brain corticotropin-releasing factor (CRF) systems and hypothalamic-pituitary-adrenal (HPA) axis function of male and female prepubertal rhesus monkeys. At 12-months-old, CSF levels of CRF were measured and HPA axis activity was characterized by examining diurnal cortisol rhythm and response to pharmacological challenges. Compared with controls, Neo-A animals showed higher cortisol secretion throughout the day, and Neo-A females also showed higher CRF levels. Hypersecretion of basal cortisol, in conjunction with blunted pituitary-adrenal responses to CRF challenge, suggest HPA axis hyperactivity caused by increased CRF hypothalamic drive leading to downregulation of pituitary CRF receptors in Neo-A animals. This interpretation is supported by the increased CRF CSF levels, suggesting that Neo-A damage resulted in central CRF systems overactivity. Neo-A animals also exhibited enhanced glucocorticoid negative feedback, as reflected by an exaggerated cortisol suppression following dexamethasone administration, indicating an additional effect on glucocorticoid receptor (GR) function. Together these data demonstrate that early amygdala damage alters the typical development of the primate HPA axis resulting in increased rather than decreased activity, presumably via alterations in central CRF and GR systems in neural structures that control its activity. Thus, in contrast to evidence that the amygdala stimulates both CRF and HPA axis systems in the adult, our data suggest an opposite, inhibitory role of the amygdala on the HPA axis during early development, which fits with emerging literature on “developmental switches” in amygdala function and connectivity with other brain areas. PMID:25143624

  20. Role of MRI in multiple sclerosis I: inflammation and lesions.

    PubMed

    Zivadinov, Robert; Bakshi, Rohit

    2004-01-01

    Conventional magnetic resonance imaging (MRI) can improve accuracy in the diagnosis of multiple sclerosis (MS). Metrics derived from conventional MRI are now routinely used to detect therapeutic effects and extend clinical observations. Hyperintense lesions on T2-weighted MRI scans are related primarily to increased water content and thus cannot distinguish between inflammation, edema, demyelination, Wallerian degeneration, and axonal loss. In addition, T2-weighted and post-contrast images are not sufficiently sensitive to detect occult disease affecting normal appearing gray and white matter. They do not show a reliable correlation with clinical measures of disability and do not provide a complete assessment of therapeutic outcomes. In the past few years a host of advanced MRI techniques and analysis methods have been introduced for the assessment of MS. These MRI techniques appear to have better reliability as surrogate markers for monitoring the pathologic processes that most likely are related to disease activity and clinical progression. They are able to reveal a range of tissue changes that include edema, inflammation, demyelination, axonal loss, and neurodegeneration. Therefore, in a disease with a high degree of longitudinal variability of clinical signs and symptoms within and between patients, and with no current adequate biological markers of disease progression, non-conventional MRI techniques provide a powerful tool to non-invasively study pathological substrates of overt lesions and normal appearing brain tissue. In particular, the use of these techniques is promising in elucidating mechanisms underlying the accumulation of tissue damage, repair and functional reorganization of neural pathways in patients with MS.

  1. Lesions of either anterior orbitofrontal cortex or ventrolateral prefrontal cortex in marmoset monkeys heighten innate fear and attenuate active coping behaviors to predator threat

    PubMed Central

    Shiba, Yoshiro; Kim, Charissa; Santangelo, Andrea M.; Roberts, Angela C.

    2015-01-01

    The ventral prefrontal cortex is an integral part of the neural circuitry that is dysregulated in mood and anxiety disorders. However, the contribution of its distinct sub-regions to the regulation of negative emotion are poorly understood. Recently we implicated both the ventrolateral prefrontal cortex (vlPFC) and anterior orbitofrontal cortex (antOFC) in the regulation of conditioned fear and anxiety responses to a social stimulus, i.e., human intruder, in the marmoset monkey. In the present study we extend our investigations to determine the role of these two regions in regulating innate responses and coping strategies to a predator stimulus, i.e., a model snake. Both the vlPFC and antOFC lesioned groups exhibited enhanced anxiety-related responses to the snake in comparison to controls. Both groups also showed a reduction in active coping behavior. These results indicate that the vlPFC and antOFC contribute independently to the regulation of both innate fear and, as previously reported, conditioned fear, and highlight the importance of these regions in producing stimulus-appropriate coping responses. The finding that dysregulation in two distinct prefrontal regions produces the apparently similar behavioral phenotype of heightened negative emotion provides insight into the varied etiology that may underlie this symptom across a wide variety of neuropsychiatric conditions with implications for personalized treatment strategies. PMID:25653599

  2. Effects of Twelve Germline Missense Variations on DNA Lesion and G-Quadruplex Bypass Activities of Human DNA Polymerase REV1.

    PubMed

    Yeom, Mina; Kim, In-Hyeok; Kim, Jae-Kwon; Kang, KyeongJin; Eoff, Robert L; Guengerich, F Peter; Choi, Jeong-Yun

    2016-03-21

    The Y-family DNA polymerase REV1 is involved in replicative bypass of damaged DNA and G-quadruplex (G4) DNA. In addition to a scaffolding role in the replicative bypass, REV1 acts in a catalytic role as a deoxycytidyl transferase opposite some replication stall sites, e.g., apurinic/apyrimidinic (AP) sites, N(2)-guanyl lesions, and G4 sites. We characterized the biochemical properties of 12 reported germline missense variants of human REV1, including the N373S variant associated with high risk of cervical cancer, using the recombinant REV1 (residues 330-833) proteins and DNA templates containing a G, AP site, N(2)-CH2(2-naphthyl)G (N(2)-NaphG), or G4. In steady-state kinetic analyses, the F427L, R434Q, M656V, D700N, R704Q, and P831L variants displayed 2- to 8-fold decreases in kcat/Km for dCTP insertion opposite all four templates, compared to that of wild-type, while the N373S, M407L, and N497S showed 2- to 3-fold increases with all four and the former three or two templates, respectively. The F427L, R434Q, M656V, and R704Q variants also had 2- to 3-fold lower binding affinities to DNA substrates containing G, an AP site, and/or N(2)-NaphG than wild-type. Distinctively, the N373S variant had a 3-fold higher binding affinity to G4 DNA than the wild-type, as well as a 2-fold higher catalytic activity opposite the first tetrad G, suggesting a facilitating effect of this variation on replication of G4 DNA sequences in certain human papillomavirus genomes. Our results suggest that the catalytic function of REV1 is moderately or slightly altered by at least nine genetic variations, and the G4 DNA processing function of REV1 is slightly enhanced by the N373S variation, which might provide the possibility that certain germline missense REV1 variations affect the individual susceptibility to carcinogenesis by modifying the capability of REV1 for replicative bypass past DNA lesions and G4 motifs derived from chemical and viral carcinogens.

  3. Classification of multiple sclerosis lesions using adaptive dictionary learning.

    PubMed

    Deshpande, Hrishikesh; Maurel, Pierre; Barillot, Christian

    2015-12-01

    This paper presents a sparse representation and an adaptive dictionary learning based method for automated classification of multiple sclerosis (MS) lesions in magnetic resonance (MR) images. Manual delineation of MS lesions is a time-consuming task, requiring neuroradiology experts to analyze huge volume of MR data. This, in addition to the high intra- and inter-observer variability necessitates the requirement of automated MS lesion classification methods. Among many image representation models and classification methods that can be used for such purpose, we investigate the use of sparse modeling. In the recent years, sparse representation has evolved as a tool in modeling data using a few basis elements of an over-complete dictionary and has found applications in many image processing tasks including classification. We propose a supervised classification approach by learning dictionaries specific to the lesions and individual healthy brain tissues, which include white matter (WM), gray matter (GM) and cerebrospinal fluid (CSF). The size of the dictionaries learned for each class plays a major role in data representation but it is an even more crucial element in the case of competitive classification. Our approach adapts the size of the dictionary for each class, depending on the complexity of the underlying data. The algorithm is validated using 52 multi-sequence MR images acquired from 13 MS patients. The results demonstrate the effectiveness of our approach in MS lesion classification.

  4. Classification of multiple sclerosis lesions using adaptive dictionary learning.

    PubMed

    Deshpande, Hrishikesh; Maurel, Pierre; Barillot, Christian

    2015-12-01

    This paper presents a sparse representation and an adaptive dictionary learning based method for automated classification of multiple sclerosis (MS) lesions in magnetic resonance (MR) images. Manual delineation of MS lesions is a time-consuming task, requiring neuroradiology experts to analyze huge volume of MR data. This, in addition to the high intra- and inter-observer variability necessitates the requirement of automated MS lesion classification methods. Among many image representation models and classification methods that can be used for such purpose, we investigate the use of sparse modeling. In the recent years, sparse representation has evolved as a tool in modeling data using a few basis elements of an over-complete dictionary and has found applications in many image processing tasks including classification. We propose a supervised classification approach by learning dictionaries specific to the lesions and individual healthy brain tissues, which include white matter (WM), gray matter (GM) and cerebrospinal fluid (CSF). The size of the dictionaries learned for each class plays a major role in data representation but it is an even more crucial element in the case of competitive classification. Our approach adapts the size of the dictionary for each class, depending on the complexity of the underlying data. The algorithm is validated using 52 multi-sequence MR images acquired from 13 MS patients. The results demonstrate the effectiveness of our approach in MS lesion classification. PMID:26055435

  5. Ghost cell lesions

    PubMed Central

    Rajesh, E.; Jimson, Sudha; Masthan, K. M. K.; Balachander, N.

    2015-01-01

    Ghost cells have been a controversy for a long time. Ghost cell is a swollen/enlarged epithelial cell with eosnophilic cytoplasm, but without a nucleus. In routine H and E staining these cells give a shadowy appearance. Hence these cells are also called as shadow cells or translucent cells. The appearance of these cells varies from lesion to lesion involving odontogenic and nonodontogenic lesions. This article review about the origin, nature and significance of ghost cells in different neoplasms. PMID:26015694

  6. White Matter Lesion Load Is Associated With Resting State Functional MRI Activity and Amyloid PET but not FDG in Mild Cognitive Impairment and Early Alzheimer's Disease Patients

    PubMed Central

    Zhou, Yongxia; Yu, Fang; Duong, Timothy Q.

    2014-01-01

    Purpose To quantify and investigate the interactions between multimodal MRI/positron emission tomography (PET) imaging metrics in elderly patients with early Alzheimer's disease (AD), mild cognitive impairment (MCI) and healthy controls. Materials and Methods Thirteen early AD, 17 MCI patients, and 14 age-matched healthy aging controls from the Alzheimer's Disease Neuroimaging Initiative database were selected based on availability of data. Default mode network (DMN) functional connectivity and fractional amplitude of low frequency fluctuation (fALFF) were obtained for resting state functional MRI (RS-fMRI). White matter lesion load (WMLL) was quantified from MRI T2-weighted FLAIR images. Amyloid deposition with PET [18F]-Florbetapir tracer and metabolism of glucose by means of [18F]-fluoro-2-deoxyglucose (FDG) images were quantified using ratio of standard uptake values (rSUV). Results Whole-brain WMLL and amyloid deposition were significantly higher (P < 0.005) in MCI and AD patients compared with controls. RS-fMRI results showed significantly reduced (corrected P < 0.05) DMN connectiv ity and altered fALFF activity in both MCI and AD groups. FDG uptake results showed hypometabolism in AD and MCI patients compared with controls. Correlations (P < 0.05) were found between WMLL and amyloid load, FDG uptake and amyloid load, as well as between amyloid load (rSUV) and fALFF. Conclusion Our quantitative results of four MRI and PET imaging metrics (fALFF/DMN, WMLL, amyloid, and FDG rSUV values) agree with published values. Signifi-cant correlations between MRI metrics, including WMLL/ functional activity and PET amyloid load suggest the potential of MRI and PET-based biomarkers for early detection of AD. PMID:24382798

  7. Follow-up of cortical activity and structure after lesion with laser speckle imaging and magnetic resonance imaging in nonhuman primates

    NASA Astrophysics Data System (ADS)

    Peuser, Jörn; Belhaj-Saif, Abderraouf; Hamadjida, Adjia; Schmidlin, Eric; Gindrat, Anne-Dominique; Völker, Andreas Charles; Zakharov, Pavel; Hoogewoud, Henri-Marcel; Rouiller, Eric M.; Scheffold, Frank

    2011-09-01

    The nonhuman primate model is suitable to study mechanisms of functional recovery following lesion of the cerebral cortex (motor cortex), on which therapeutic strategies can be tested. To interpret behavioral data (time course and extent of functional recovery), it is crucial to monitor the properties of the experimental cortical lesion, induced by infusion of the excitotoxin ibotenic acid. In two adult macaque monkeys, ibotenic acid infusions produced a restricted, permanent lesion of the motor cortex. In one monkey, the lesion was monitored over 3.5 weeks, combining laser speckle imaging (LSI) as metabolic readout (cerebral blood flow) and anatomical assessment with magnetic resonance imaging (T2-weighted MRI). The cerebral blood flow, measured online during subsequent injections of the ibotenic acid in the motor cortex, exhibited a dramatic increase, still present after one week, in parallel to a MRI hypersignal. After 3.5 weeks, the cerebral blood flow was strongly reduced (below reference level) and the hypersignal disappeared from the MRI scan, although the lesion was permanent as histologically assessed post-mortem. The MRI data were similar in the second monkey. Our experiments suggest that LSI and MRI, although they reflect different features, vary in parallel during a few weeks following an excitotoxic cortical lesion.

  8. GC/MS Evaluation and In Vitro Antioxidant Activity of Essential Oil and Solvent Extracts of an Endemic Plant Used as Folk Remedy in Turkey: Phlomis bourgaei Boiss.

    PubMed Central

    Sarikurkcu, Cengiz; Sabih Ozer, M.; Cakir, Ahmet; Eskici, Mustafa; Mete, Ebru

    2013-01-01

    This study was outlined to examine the chemical composition of hydrodistilled essential oil and in vitro antioxidant potentials of the essential oil and different solvent extracts of endemic Phlomis bourgaei Boiss. used as folk remedy in Turkey. The chemical composition of the oil was analyzed by GC and GC-MS, and the predominant components in the oil were found to be β-caryophyllene (37.37%), (Z)-β-farnesene (15.88%), and germacrene D (10.97%). Antioxidant potentials of the solvent extracts and the oil were determined by four testing systems including β-carotene/linoleic acid, DPPH, reducing power, and chelating effect. In β-carotene/linoleic acid assay, all extracts showed the inhibition of more than 50% at all concentrations. In DPPH, chelating effect, and reducing power test systems, the water extract with 88.68%, 77.45%, and 1.857 (absorbance at 700 nm), respectively, exhibited more excellent activity potential than other extracts (hexane, ethyl acetate and methanol) and the essential oil at 1.0 mg/mL concentration. The amount of the total phenolics and flavonoids was the highest in this extract (139.50 ± 3.98 μg gallic acid equivalents (GAEs)/mg extract and 22.71 ± 0.05 μg quercetin equivalents (QEs)/mg extract). PMID:23762120

  9. Fragrances and other materials in deodorants: search for potentially sensitizing molecules using combined GC-MS and structure activity relationship (SAR) analysis.

    PubMed

    Rastogi, S C; Lepoittevin, J P; Johansen, J D; Frosch, P J; Menné, T; Bruze, M; Dreier, B; Andersen, K E; White, I R

    1998-12-01

    Deodorants are one of the most frequently-used types of cosmetics and are a source of allergic contact dermatitis. Therefore, a gas chromatography - mass spectrometric analysis of 71 deodorants was performed for identification of fragrance and non-fragrance materials present in marketed deodorants. Futhermore, the sensitizing potential of these molecules was evaluated using structure activity relationships (SARs) analysis. This was based on the presence of 1 or more chemically reactive site(s), in the chemical structure, associated with sensitizing potential. Among the many different substances used to formulate cosmetic products (over 3500), 226 chemicals were identified in a sample of 71 deodorants. 84 molecules were found to contain at least 1 structural alert, and 70 to belong to, or be susceptible to being metabolized into, the chemical group of aldehydes, ketones and alpha,beta-unsaturated aldehydes, ketone or esters. The combination of GC-MS and SARs analysis could be helpful in the selection of substances for supplementary investigations regarding sensitizing properties. Thus, it may be a valuable tool in the management of contact allergy to deodorants and for producing new deodorants with decreased propensity to cause contact allergy.

  10. GC/MS Evaluation and In Vitro Antioxidant Activity of Essential Oil and Solvent Extracts of an Endemic Plant Used as Folk Remedy in Turkey: Phlomis bourgaei Boiss.

    PubMed

    Sarikurkcu, Cengiz; Sabih Ozer, M; Cakir, Ahmet; Eskici, Mustafa; Mete, Ebru

    2013-01-01

    This study was outlined to examine the chemical composition of hydrodistilled essential oil and in vitro antioxidant potentials of the essential oil and different solvent extracts of endemic Phlomis bourgaei Boiss. used as folk remedy in Turkey. The chemical composition of the oil was analyzed by GC and GC-MS, and the predominant components in the oil were found to be β -caryophyllene (37.37%), (Z)- β -farnesene (15.88%), and germacrene D (10.97%). Antioxidant potentials of the solvent extracts and the oil were determined by four testing systems including β -carotene/linoleic acid, DPPH, reducing power, and chelating effect. In β -carotene/linoleic acid assay, all extracts showed the inhibition of more than 50% at all concentrations. In DPPH, chelating effect, and reducing power test systems, the water extract with 88.68%, 77.45%, and 1.857 (absorbance at 700 nm), respectively, exhibited more excellent activity potential than other extracts (hexane, ethyl acetate and methanol) and the essential oil at 1.0 mg/mL concentration. The amount of the total phenolics and flavonoids was the highest in this extract (139.50 ± 3.98  μ g gallic acid equivalents (GAEs)/mg extract and 22.71 ± 0.05 μ g quercetin equivalents (QEs)/mg extract). PMID:23762120

  11. Comprehensive analysis of human endogenous retrovirus group HERV-W locus transcription in multiple sclerosis brain lesions by high-throughput amplicon sequencing.

    PubMed

    Schmitt, Katja; Richter, Christin; Backes, Christina; Meese, Eckart; Ruprecht, Klemens; Mayer, Jens

    2013-12-01

    Human endogenous retroviruses (HERVs) of the HERV-W group comprise hundreds of loci in the human genome. Deregulated HERV-W expression and HERV-W locus ERVWE1-encoded Syncytin-1 protein have been implicated in the pathogenesis of multiple sclerosis (MS). However, the actual transcription of HERV-W loci in the MS context has not been comprehensively analyzed. We investigated transcription of HERV-W in MS brain lesions and white matter brain tissue from healthy controls by employing next-generation amplicon sequencing of HERV-W env-specific reverse transcriptase (RT) PCR products, thus revealing transcribed HERV-W loci and the relative transcript levels of those loci. We identified more than 100 HERV-W loci that were transcribed in the human brain, with a limited number of loci being predominantly transcribed. Importantly, relative transcript levels of HERV-W loci were very similar between MS and healthy brain tissue samples, refuting deregulated transcription of HERV-W env in MS brain lesions, including the high-level-transcribed ERVWE1 locus encoding Syncytin-1. Quantitative RT-PCR likewise did not reveal differences in MS regarding HERV-W env general transcript or ERVWE1- and ERVWE2-specific transcript levels. However, we obtained evidence for interindividual differences in HERV-W transcript levels. Reporter gene assays indicated promoter activity of many HERV-W long terminal repeats (LTRs), including structurally incomplete LTRs. Our comprehensive analysis of HERV-W transcription in the human brain thus provides important information on the biology of HERV-W in MS lesions and normal human brain, implications for study design, and mechanisms by which HERV-W may (or may not) be involved in MS.

  12. Quantification of sphingosine 1-phosphate by validated LC-MS/MS method revealing strong correlation with apolipoprotein M in plasma but not in serum due to platelet activation during blood coagulation.

    PubMed

    Frej, Cecilia; Andersson, Anders; Larsson, Benny; Guo, Li Jun; Norström, Eva; Happonen, Kaisa E; Dahlbäck, Björn

    2015-11-01

    Sphingosine 1-phosphate (S1P) is a signalling sphingolipid affecting multiple cellular functions of vascular and immune systems. It circulates at submicromolar levels bound to HDL-associated apolipoprotein M (apoM) or to albumin. S1P in blood is mainly produced by platelets and erythrocytes, making blood sampling for S1P quantification delicate. Standardisation of sampling is thereby of great importance to obtain robust data. By optimising and characterising the extraction procedure and the LC-MS/MS analysis, we have developed and validated a highly specific and sensitive method for S1P quantification. Blood was collected from healthy individuals (n = 15) to evaluate the effects of differential blood sampling on S1P levels. To evaluate correlation between S1P and apoM in different types of plasma and serum, apoM was measured by ELISA. The method showed good accuracy and precision in the range of 0.011 to 0.9 μM with less than 0.07 % carryover. We found that the methanol precipitation used to extract S1P co-extracted apoM and several other HDL-proteins from plasma. The platelet-associated S1P was released during coagulation, thus increasing the S1P concentration to double in serum as compared to that in plasma. Gel filtration chromatography revealed that the platelet-released S1P was mainly bound to albumin. This explains why the strong correlation between S1P and apoM levels in plasma is lost upon the clotting process and hence not observed in serum. We have developed, characterised and validated an efficient, highly sensitive and specific method for the quantification of S1P in biological material.

  13. Activation of endogenous neural stem cells for multiple sclerosis therapy.

    PubMed

    Michailidou, Iliana; de Vries, Helga E; Hol, Elly M; van Strien, Miriam E

    2014-01-01

    Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system, leading to severe neurological deficits. Current MS treatment regimens, consist of immunomodulatory agents aiming to reduce the rate of relapses. However, these agents are usually insufficient to treat chronic neurological disability. A promising perspective for future therapy of MS is the regeneration of lesions with replacement of the damaged oligodendrocytes or neurons. Therapies targeting to the enhancement of endogenous remyelination, aim to promote the activation of either the parenchymal oligodendrocyte progenitor cells or the subventricular zone-derived neural stem cells (NSCs). Less studied but highly potent, is the strategy of neuronal regeneration with endogenous NSCs that although being linked to numerous limitations, is anticipated to ameliorate cognitive disability in MS. Focusing on the forebrain, this review highlights the role of NSCs in the regeneration of MS lesions.

  14. Activation of endogenous neural stem cells for multiple sclerosis therapy

    PubMed Central

    Michailidou, Iliana; de Vries, Helga E.; Hol, Elly M.; van Strien, Miriam E.

    2015-01-01

    Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system, leading to severe neurological deficits. Current MS treatment regimens, consist of immunomodulatory agents aiming to reduce the rate of relapses. However, these agents are usually insufficient to treat chronic neurological disability. A promising perspective for future therapy of MS is the regeneration of lesions with replacement of the damaged oligodendrocytes or neurons. Therapies targeting to the enhancement of endogenous remyelination, aim to promote the activation of either the parenchymal oligodendrocyte progenitor cells or the subventricular zone-derived neural stem cells (NSCs). Less studied but highly potent, is the strategy of neuronal regeneration with endogenous NSCs that although being linked to numerous limitations, is anticipated to ameliorate cognitive disability in MS. Focusing on the forebrain, this review highlights the role of NSCs in the regeneration of MS lesions. PMID:25653584

  15. Preinvasive lesions

    Cancer.gov

    This definition is for allocation of lesions with preinvasive/borderline properties. It is currently aimed at newly identified neoplasms, which may be similar to those described in humans. In mouse pathology, many adenomas may be preinvasive/borderline lesions. However, their inclusion in the preinvasive category can be justified only upon development of better diagnostic criteria.

  16. Multi-output decision trees for lesion segmentation in multiple sclerosis

    NASA Astrophysics Data System (ADS)

    Jog, Amod; Carass, Aaron; Pham, Dzung L.; Prince, Jerry L.

    2015-03-01

    Multiple Sclerosis (MS) is a disease of the central nervous system in which the protective myelin sheath of the neurons is damaged. MS leads to the formation of lesions, predominantly in the white matter of the brain and the spinal cord. The number and volume of lesions visible in magnetic resonance (MR) imaging (MRI) are important criteria for diagnosing and tracking the progression of MS. Locating and delineating lesions manually requires the tedious and expensive efforts of highly trained raters. In this paper, we propose an automated algorithm to segment lesions in MR images using multi-output decision trees. We evaluated our algorithm on the publicly available MICCAI 2008 MS Lesion Segmentation Challenge training dataset of 20 subjects, and showed improved results in comparison to state-of-the-art methods. We also evaluated our algorithm on an in-house dataset of 49 subjects with a true positive rate of 0.41 and a positive predictive value 0.36.

  17. Multi-Output Decision Trees for Lesion Segmentation in Multiple Sclerosis

    PubMed Central

    Jog, Amod; Carass, Aaron; Pham, Dzung L.; Prince, Jerry L.

    2016-01-01

    Multiple Sclerosis (MS) is a disease of the central nervous system in which the protective myelin sheath of the neurons is damaged. MS leads to the formation of lesions, predominantly in the white matter of the brain and the spinal cord. The number and volume of lesions visible in magnetic resonance (MR) imaging (MRI) are important criteria for diagnosing and tracking the progression of MS. Locating and delineating lesions manually requires the tedious and expensive efforts of highly trained raters. In this paper, we propose an automated algorithm to segment lesions in MR images using multi-output decision trees. We evaluated our algorithm on the publicly available MICCAI 2008 MS Lesion Segmentation Challenge training dataset of 20 subjects, and showed improved results in comparison to state-of-the-art methods. We also evaluated our algorithm on an in-house dataset of 49 subjects with a true positive rate of 0.41 and a positive predictive value 0.36.

  18. Cannabinoids and neuronal damage: differential effects of THC, AEA and 2-AG on activated microglial cells and degenerating neurons in excitotoxically lesioned rat organotypic hippocampal slice cultures.

    PubMed

    Kreutz, Susanne; Koch, Marco; Ghadban, Chalid; Korf, Horst-Werner; Dehghani, Faramarz

    2007-01-01

    Cannabinoids (CBs) are attributed neuroprotective effects in vivo. Here, we determined the neuroprotective potential of CBs during neuronal damage in excitotoxically lesioned organotypic hippocampal slice cultures (OHSCs). OHSCs are the best characterized in vitro model to investigate the function of microglial cells in neuronal damage since blood-borne monocytes and T-lymphocytes are absent and microglial cells represent the only immunocompetent cell type. Excitotoxic neuronal damage was induced by NMDA (50 microM) application for 4 h. Neuroprotective properties of 9-carboxy-11-nor-delta-9-tetrahydrocannabinol (THC), N-arachidonoylethanolamide (AEA) or 2-arachidonoylglycerol (2-AG) in different concentrations were determined after co-application with NMDA by counting degenerating neurons identified by propidium iodide labeling (PI(+)) and microglial cells labeled by isolectin B(4) (IB(4)(+)). All three CBs used significantly decreased the number of IB(4)(+) microglial cells in the dentate gyrus but the number of PI(+) neurons was reduced only after 2-AG treatment. Application of AM630, antagonizing CB2 receptors highly expressed by activated microglial cells, did not counteract neuroprotective effects of 2-AG, but affected THC-mediated reduction of IB(4)(+) microglial cells. Our results indicate that (1) only 2-AG exerts neuroprotective effects in OHSCs; (2) reduction of IB(4)(+) microglial cells is not a neuroprotective event per se and involves other CB receptors than the CB2 receptor; (3) the discrepancy in the neuroprotective effects of CBs observed in vivo and in our in vitro model system may underline the functional relevance of invading monocytes and T-lymphocytes that are absent in OHSCs. PMID:17010339

  19. Imaging Pediatric Vascular Lesions

    PubMed Central

    Nguyen, Tuyet A.; Krakowski, Andrew C.; Naheedy, John H.; Kruk, Peter G.

    2015-01-01

    Vascular anomalies are commonly encountered in pediatric and dermatology practices. Most of these lesions are benign and easy to diagnose based on history and clinical exam alone. However, in some cases the diagnosis may not be clear. This may be of particular concern given that vascular anomalies may occasionally be associated with an underlying syndrome, congenital disease, or serious, life-threatening condition. Defining the type of vascular lesion early and correctly is particularly important to determine the optimal approach to management and treatment of each patient. The care of pediatric patients often requires collaboration from a multitude of specialties including pediatrics, dermatology, plastic surgery, radiology, ophthalmology, and neurology. Although early characterization of vascular lesions is important, consensus guidelines regarding the evaluation and imaging of vascular anomalies does not exist to date. Here, the authors provide an overview of pediatric vascular lesions, current classification systems for characterizing these lesions, the various imaging modalities available, and recommendations for appropriate imaging evaluation. PMID:26705446

  20. Extragastric Dieulafoy's lesion

    PubMed Central

    Gauci, James; Galea, Samuel; Galea, Joseph; Schembri, Mark

    2014-01-01

    A 74-year-old man on warfarin for aortic valve replacement presented with recurrent episodes of melaena. An initial oesophagogastroduodenoscopy (OGD) was normal, as were red cell scanning and colonoscopy. It was a third OGD that revealed the cause of the melaena—a vascular lesion in the duodenum, at the junction between D1 and D2. An extragastric Dieulafoy's lesion was diagnosed, and the lesion was injected with epinephrine and tattooed. Over the following months, episodes of bleeding recurred despite further attempts at injection. Percutaneous radiologically assisted embolisation of the gastroduodenal artery, and eventually duodenotomy and oversuturing of the lesion were performed to no avail. The patient has undergone over 10 endoscopies, and has received over 70 units of packed red cells to date, since his initial presentation 6 years ago. Attempts to stop the bleeding permanently have been difficult, highlighting the complexity of managing such a lesion. PMID:25216921

  1. Simultaneous determination of curcumin diethyl disuccinate and its active metabolite curcumin in rat plasma by LC-MS/MS: Application of esterase inhibitors in the stabilization of an ester-containing prodrug.

    PubMed

    Ratnatilaka Na Bhuket, Pahweenvaj; Niwattisaiwong, Nuansri; Limpikirati, Patanachai; Khemawoot, Phisit; Towiwat, Pasarapa; Ongpipattanakul, Boonsri; Rojsitthisak, Pornchai

    2016-10-15

    Four esterase inhibitors, ethylenediamine tetraacetic acid disodium (Na2EDTA), sodium fluoride (NaF), bis(4-nitrophenyl) phosphate (BNPP) and phenylmethanesulfonyl fluoride (PMSF), were evaluated for their inhibitory effects on enzymatic hydrolysis of labile phenolate esters in curcumin diethyl disuccinate (CDD), a prodrug of curcumin (CUR), in rat plasma. BNPP and PMSF at 10mM exhibited stabilization by preventing degradation of CDD. BNPP at a final concentration of 10mM was subsequently selected to prevent ex vivo metabolism of CDD throughout LC-MS/MS analysis of CDD and CUR in rat plasma. A simple protein precipitation technique using acetonitrile as a precipitating agent was used to extract CDD, CUR and dimethylcurcumin (DMC), an internal standard, from rat plasma. Chromatographic separation was performed on a Halo C8 column (4.6×50mm, 2.7μm) using an isocratic mobile phase containing acetonitrile-0.2% formic acid in water (73:27v/v) with a flow rate of 0.4mLmin(-1). An AB SCIEX QTRAP(®) 6500 mass spectrometer was operated using a positive ion electrospray mode for ionization and detection of analytes and internal standard. Calibration curves for CDD and CUR were established using 50μL of rat plasma over the concentration range of 1-500ngmL(-1). The developed method was fully validated according to US Food and Drug Administration (FDA) guidelines for selectivity, sensitivity, linearity, accuracy, precision, dilution integrity, recovery, matrix effect, and stability. The validated method was applied to evaluate the pharmacokinetics of CDD and CUR in rats after a single intravenous dose of 40mgkg(-1). The method using BNPP as an esterase inhibitor was successful in determining the remaining CDD in rat plasma. The pharmacokinetic results indicate that CDD in rats is converted instantaneously to CUR after intravenous administration and a higher CUR plasma concentration at 5min is achieved in comparison with direct intravenous injection of CUR. PMID:27595650

  2. MRI phase changes in multiple sclerosis vs neuromyelitis optica lesions at 7T

    PubMed Central

    Sinnecker, Tim; Schumacher, Sophie; Mueller, Katharina; Pache, Florence; Dusek, Petr; Harms, Lutz; Ruprecht, Klemens; Nytrova, Petra; Chawla, Sanjeev; Niendorf, Thoralf; Kister, Ilya; Ge, Yulin; Wuerfel, Jens

    2016-01-01

    Objective: To characterize paramagnetic MRI phase signal abnormalities in neuromyelitis optica spectrum disorder (NMOSD) vs multiple sclerosis (MS) lesions in a cross-sectional study. Methods: Ten patients with NMOSD and 10 patients with relapsing-remitting MS underwent 7-tesla brain MRI including supratentorial T2*-weighted imaging and supratentorial susceptibility weighted imaging. Next, we analyzed intra- and perilesional paramagnetic phase changes on susceptibility weighted imaging filtered magnetic resonance phase images. Results: We frequently observed paramagnetic rim-like (75 of 232 lesions, 32%) or nodular (32 of 232 lesions, 14%) phase changes in MS lesions, but only rarely in NMOSD lesions (rim-like phase changes: 2 of 112 lesions, 2%, p < 0.001; nodular phase changes: 2 of 112 lesions, 2%, p < 0.001). Conclusions: Rim-like or nodular paramagnetic MRI phase changes are characteristic for MS lesions and not frequently detectable in NMOSD. Future prospective studies should ask whether these imaging findings can be used as a biomarker to distinguish between NMOSD- and MS-related brain lesions. PMID:27489865

  3. Sensitivity of GC-EI/MS, GC-EI/MS/MS, LC-ESI/MS/MS, LC-Ag(+) CIS/MS/MS, and GC-ESI/MS/MS for analysis of anabolic steroids in doping control.

    PubMed

    Cha, Eunju; Kim, Sohee; Kim, Ho Jun; Lee, Kang Mi; Kim, Ki Hun; Kwon, Oh-Seung; Lee, Jaeick

    2015-01-01

    This study compared the sensitivity of various separation and ionization methods, including gas chromatography with an electron ionization source (GC-EI), liquid chromatography with an electrospray ionization source (LC-ESI), and liquid chromatography with a silver ion coordination ion spray source (LC-Ag(+) CIS), coupled to a mass spectrometer (MS) for steroid analysis. Chromatographic conditions, mass spectrometric transitions, and ion source parameters were optimized. The majority of steroids in GC-EI/MS/MS and LC-Ag(+) CIS/MS/MS analysis showed higher sensitivities than those obtained with other analytical methods. The limits of detection (LODs) of 65 steroids by GC-EI/MS/MS, 68 steroids by LC-Ag(+) CIS/MS/MS, 56 steroids by GC-EI/MS, 54 steroids by LC-ESI/MS/MS, and 27 steroids by GC-ESI/MS/MS were below cut-off value of 2.0 ng/mL. LODs of steroids that formed protonated ions in LC-ESI/MS/MS analysis were all lower than the cut-off value. Several steroids such as unconjugated C3-hydroxyl with C17-hydroxyl structure showed higher sensitivities in GC-EI/MS/MS analysis relative to those obtained using the LC-based methods. The steroids containing 4, 9, 11-triene structures showed relatively poor sensitivities in GC-EI/MS and GC-ESI/MS/MS analysis. The results of this study provide information that may be useful for selecting suitable analytical methods for confirmatory analysis of steroids.

  4. Sensitivity of GC-EI/MS, GC-EI/MS/MS, LC-ESI/MS/MS, LC-Ag(+) CIS/MS/MS, and GC-ESI/MS/MS for analysis of anabolic steroids in doping control.

    PubMed

    Cha, Eunju; Kim, Sohee; Kim, Ho Jun; Lee, Kang Mi; Kim, Ki Hun; Kwon, Oh-Seung; Lee, Jaeick

    2015-01-01

    This study compared the sensitivity of various separation and ionization methods, including gas chromatography with an electron ionization source (GC-EI), liquid chromatography with an electrospray ionization source (LC-ESI), and liquid chromatography with a silver ion coordination ion spray source (LC-Ag(+) CIS), coupled to a mass spectrometer (MS) for steroid analysis. Chromatographic conditions, mass spectrometric transitions, and ion source parameters were optimized. The majority of steroids in GC-EI/MS/MS and LC-Ag(+) CIS/MS/MS analysis showed higher sensitivities than those obtained with other analytical methods. The limits of detection (LODs) of 65 steroids by GC-EI/MS/MS, 68 steroids by LC-Ag(+) CIS/MS/MS, 56 steroids by GC-EI/MS, 54 steroids by LC-ESI/MS/MS, and 27 steroids by GC-ESI/MS/MS were below cut-off value of 2.0 ng/mL. LODs of steroids that formed protonated ions in LC-ESI/MS/MS analysis were all lower than the cut-off value. Several steroids such as unconjugated C3-hydroxyl with C17-hydroxyl structure showed higher sensitivities in GC-EI/MS/MS analysis relative to those obtained using the LC-based methods. The steroids containing 4, 9, 11-triene structures showed relatively poor sensitivities in GC-EI/MS and GC-ESI/MS/MS analysis. The results of this study provide information that may be useful for selecting suitable analytical methods for confirmatory analysis of steroids. PMID:26489966

  5. Autoimmune control of lesion growth in CNS with minimal damage

    NASA Astrophysics Data System (ADS)

    Mathankumar, R.; Mohan, T. R. Krishna

    2013-07-01

    Lesions in central nervous system (CNS) and their growth leads to debilitating diseases like Multiple Sclerosis (MS), Alzheimer's etc. We developed a model earlier [1, 2] which shows how the lesion growth can be arrested through a beneficial auto-immune mechanism. We compared some of the dynamical patterns in the model with different facets of MS. The success of the approach depends on a set of control parameters and their phase space was shown to have a smooth manifold separating the uncontrolled lesion growth region from the controlled. Here we show that an optimal set of parameter values exist in the model which minimizes system damage while, at once, achieving control of lesion growth.

  6. Primary-Progressive MS (PPMS)

    MedlinePlus

    ... MS? Types of MS Primary progressive MS (PPMS) Primary progressive MS (PPMS) Share Smaller Text Larger Text Print In this article Overview PPMS is characterized by worsening neurologic function ( ...

  7. Fimbria-fornix lesions impair spatial performance and induce epileptic-like activity but do not affect long-term potentiation in the CA1 region of rat hippocampal slices.

    PubMed

    Kleschevnikov, A M; Sinden, J D; Marchbanks, R

    1994-09-12

    Groups of rats were given bilateral fimbria-fornix lesions and one month later grafted into the hippocampus with fetal cholinergic and non-cholinergic (hippocampal) neural tissue. Three weeks and 3 months after transplantation the animals were trained to find and then to retain the location of a hidden platform in the Morris water maze. After the final behavioral testing phase, electrophysiological studies of the short- and long-term potentiation (STP and LTP) and epileptiform activity of evoked responses were performed in vitro in the CA1 region of the hippocampus. The lesions produced a marked deficit in spatial function in the early testing phase which showed some recovery at the three month time point. Neither the cholinergic nor the non-cholinergic grafts improved spatial performance; indeed, on some measures these groups showed a significantly greater deficit than the lesion-alone group. Epileptiform activity, which was defined as the ratio of the sum of amplitudes of second and third population spikes to the amplitude of the first, before tetanization was not significantly different for all groups. After tetanization of the radiatum input, however, the epileptiform activity in the FFL group was significantly higher in comparison to that of the control groups. Grafting of cholinergic tissue decreased this parameter to the control level, but non-cholinergic grafts did not modify the lesion-induced epileptiform activity. Epileptiform activity after tetanization of the oriens input was approximately equal for all groups. There were no significant differences between surgical groups in STP and LTP for both the oriens and radiatum inputs.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. D-α-tocopheryl polyethylene glycol 1000 succinate: a view from FTICR MS and tandem MS.

    PubMed

    Wei, Juan; Bristow, Anthony; McBride, Eileen; Kilgour, David; O'Connor, Peter B

    2014-02-01

    D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) is an important polymeric excipient frequently used in drug formulation. However, differing compositions of the TPGS samples between batches are believed to result in variable performance of the formulated product. Herein, a high performance method using Fourier-transform ion cyclotron resonance (FTICR) mass spectrometry (MS) and tandem mass spectrometry (MS/MS) to analyze the composition of TPGS samples and the structure of TPGS was established. Aided by high mass accuracy and high resolution, the full MS overview of TPGS is able to provide composition information, and diagnostic fragments from collisionally activated dissociation (CAD) and electron capture dissociation (ECD) MS/MS can be used for the identification of the TPGS structure. ECD and CAD show different preferences in bond cleavage, and an interesting cross-ring cleavage was generated by CAD. Fragmentation information from ECD/ECD MS(3) is useful for providing confidence in the results. The influence of different ionization agents (Na(+), Li(+), and Ag(+)) on fragmentation of TPGS was investigated with the silver adduct providing different fragments. In addition to the methodology study, the MS and MS/MS results from four batches of TPGS samples from two manufacturers were compared. This method can be utilized for the composition and structure study of many other polymeric compounds. FTICR MS/MS demonstrated its promising role as a structural characterization tool complementary to traditional spectroscopy techniques.

  9. Multifocal vascular lesions.

    PubMed

    Levin, Laura E; Lauren, Christine T

    2016-03-01

    Multifocal vascular lesions are important to recognize and appropriately diagnose. Generally first noticed on the skin, multifocal vascular lesions may have systemic involvement. Distinguishing among the different types of multifocal vascular lesions is often based on clinical features; however, radiological imaging and/or biopsy are frequently needed to identify distinct features and guide treatment. Knowledge of the systemic associations that can occur with different vascular anomalies may reduce life-threatening complications, such as coagulopathy, bleeding, cardiac compromise, and neurologic sequelae. This review provides a synopsis of the epidemiology, pathogenesis, presentation, workup, and treatment of several well-recognized multifocal vascular tumors and malformations. PMID:27607324

  10. Oral Lesions in Neonates

    PubMed Central

    Rao, Roopa S; Majumdar, Barnali; Jafer, Mohammed; Maralingannavar, Mahesh; Sukumaran, Anil

    2016-01-01

    ABSTRACT Oral lesions in neonates represent a wide range of diseases often creating apprehension and anxiety among parents. Early examination and prompt diagnosis can aid in prudent management and serve as baseline against the future course of the disease. The present review aims to enlist and describe the diagnostic features of commonly encountered oral lesions in neonates. How to cite this article: Patil S, Rao RS, Majumdar B, Jafer M, Maralingannavar M, Sukumaran A. Oral Lesions in Neonates. Int J Clin Pediatr Dent 2016;9(2):131-138. PMID:27365934

  11. Retinal lesions in septicemia.

    PubMed

    Neudorfer, M; Barnea, Y; Geyer, O; Siegman-Igra, Y

    1993-12-15

    We explored the association between septicemia and specific retinal lesions in a prospective controlled study. Hemorrhages, cotton-wool spots, or Roth's spots were found in 24 of 101 septicemic patients (24%), compared to four of 99 age- and gender-matched control patients (4%) (P = .0002). There was no significant association between types of organisms or focus of infection and the presence of specific lesions. Histologic examination of affected eyes disclosed cytoid bodies in the nerve fiber layer without inflammation. A definite association between septicemia and retinal lesions was found and indicates the need for routine ophthalmoscopy in septicemic patients. PMID:8250076

  12. SLAP lesions: a treatment algorithm.

    PubMed

    Brockmeyer, Matthias; Tompkins, Marc; Kohn, Dieter M; Lorbach, Olaf

    2016-02-01

    Tears of the superior labrum involving the biceps anchor are a common entity, especially in athletes, and may highly impair shoulder function. If conservative treatment fails, successful arthroscopic repair of symptomatic SLAP lesions has been described in the literature particularly for young athletes. However, the results in throwing athletes are less successful with a significant amount of patients who will not regain their pre-injury level of performance. The clinical results of SLAP repairs in middle-aged and older patients are mixed, with worse results and higher revision rates as compared to younger patients. In this population, tenotomy or tenodesis of the biceps tendon is a viable alternative to SLAP repairs in order to improve clinical outcomes. The present article introduces a treatment algorithm for SLAP lesions based upon the recent literature as well as the authors' clinical experience. The type of lesion, age of patient, concomitant lesions, and functional requirements, as well as sport activity level of the patient, need to be considered. Moreover, normal variations and degenerative changes in the SLAP complex have to be distinguished from "true" SLAP lesions in order to improve results and avoid overtreatment. The suggestion for a treatment algorithm includes: type I: conservative treatment or arthroscopic debridement, type II: SLAP repair or biceps tenotomy/tenodesis, type III: resection of the instable bucket-handle tear, type IV: SLAP repair (biceps tenotomy/tenodesis if >50 % of biceps tendon is affected), type V: Bankart repair and SLAP repair, type VI: resection of the flap and SLAP repair, and type VII: refixation of the anterosuperior labrum and SLAP repair.

  13. A marine-derived Streptomyces sp. MS449 produces high yield of actinomycin X2 and actinomycin D with potent anti-tuberculosis activity.

    PubMed

    Chen, Caixia; Song, Fuhang; Wang, Qian; Abdel-Mageed, Wael M; Guo, Hui; Fu, Chengzhang; Hou, Weiyuan; Dai, Huanqin; Liu, Xueting; Yang, Na; Xie, Feng; Yu, Ke; Chen, Ruxian; Zhang, Lixin

    2012-08-01

    In the course of our screening program for anti-Mycobacterium bovis bacillus Calmette-Guérin (BCG) and anti-Mycobacterium tuberculosis H37Rv (MTB H37Rv) agents from our marine natural product library, a newly isolated actinomycete strain, designated as MS449, was picked out for further investigation. The strain MS449, isolated from a sediment sample collected from South China Sea, produced actinomycin X(2) and actinomycin D in substantial quantities, which showed strong inhibition of BCG and MTB H37Rv. The structures of actinomycins were elucidated by nuclear magnetic resonance and mass spectrometric analysis. The strain MS449 was taxonomically characterized on the basis of morphological and phenotypic characteristics, genotypic data, and phylogenetic analysis. The 16S rRNA gene sequence of the strain was determined and a database search indicated that the strain was closely associated with the type strain of Streptomyces avermitilis (99.7 % 16S rRNA gene similarity). S. avermitilis has not been previously reported to produce actinomycins. The marine-derived strain of Streptomyces sp. MS449 produced notably higher quantities of actinomycin X(2) (1.92 mg/ml) and actinomycin D (1.77 mg/ml) than previously reported actinomycins producing strains. Thus, MS449 was considered of great potential as a new industrial producing strain of actinomycin X(2) and actinomycin D.

  14. Alpha-B-crystallin induces an immune-regulatory and antiviral microglial response in preactive multiple sclerosis lesions.

    PubMed

    Bsibsi, Malika; Holtman, Inge R; Gerritsen, Wouter H; Eggen, Bart J L; Boddeke, Erik; van der Valk, Paul; van Noort, Johannes M; Amor, Sandra

    2013-10-01

    Microglial nodules are frequently observed in the normal-appearing white matter of multiple sclerosis (MS) patients. Previously, we have shown that these clusters, which we call "preactive MS lesions," are closely associated with stressed oligodendrocytes and myelin sheaths that contain markedly elevated levels of the small stress protein alpha-B-crystallin (HspB5). Here, we show that microglia in these lesions express the recently identified receptors for HspB5, that is, CD14, Toll-like receptor family 1 and 2 (TLR1 and TLR2), and several molecular markers of the microglial response to HspB5. These markers were identified by genome-wide transcript profiling of 12 primary human microglial cultures at 2 time points after exposure to HspB5. These data indicate that HspB5 activates production by microglia of an array of chemokines, immune-regulatory mediators, and a striking number of antiviral genes that are generally inducible by type I interferons. Together, our data suggest that preactive MS lesions are at least in part driven by HspB5 derived from stressed oligodendrocytes and may reflect a local attempt to restore tissue homeostasis.

  15. Ms. Mentor Unmasked

    ERIC Educational Resources Information Center

    Krebs, Paula

    2008-01-01

    This article presents an interview with Emily Toth, who writes the monthly "Ms. Mentor" academic advice column in the "Chronicle of Higher Education" and teaches in the English department at Louisiana State University, in Baton Rouge. She is the author of "Ms. Mentor's Impeccable Advice for Women in Academia" (1997), "Inside Peyton Place: The Life…

  16. The Impact of Anterior Thalamic Lesions on Active and Passive Spatial Learning in Stimulus Controlled Environments: Geometric Cues and Pattern Arrangement

    PubMed Central

    2014-01-01

    The anterior thalamic nuclei are vital for many spatial tasks. To determine more precisely their role, the present study modified the conventional Morris watermaze task. In each of 3 experiments, rats were repeatedly placed on a submerged platform in 1 corner (the ‘correct’ corner) of either a rectangular pool (Experiment 1) or a square pool with walls of different appearances (Experiments 2 and 3). The rats were then released into the pool for a first test trial in the absence of the platform. In Experiment 1, normal rats distinguished the 2 sets of corners in the rectangular pool by their geometric properties, preferring the correct corner and its diagonally opposite partner. Anterior thalamic lesions severely impaired this discrimination. In Experiments 2 and 3, normal rats typically swam directly to the correct corner of the square pool on the first test trial. Rats with anterior thalamic lesions, however, often failed to initially select the correct corner, taking more time to reach that location. Nevertheless, the lesioned rats still showed a subsequent preference for the correct corner. The same lesioned rats also showed no deficits in Experiments 2 and 3 when subsequently trained to swim to the correct corner over repeated trials. The findings show how the anterior thalamic nuclei contribute to multiple aspects of spatial processing. These thalamic nuclei may be required to distinguish relative dimensions (Experiment 1) as well as translate the appearance of spatial cues when viewed for the first time from different perspectives (Experiments 2, 3). PMID:24773436

  17. The impact of anterior thalamic lesions on active and passive spatial learning in stimulus controlled environments: geometric cues and pattern arrangement.

    PubMed

    Dumont, Julie R; Wright, Nicholas F; Pearce, John M; Aggleton, John P

    2014-04-01

    The anterior thalamic nuclei are vital for many spatial tasks. To determine more precisely their role, the present study modified the conventional Morris watermaze task. In each of 3 experiments, rats were repeatedly placed on a submerged platform in 1 corner (the 'correct' corner) of either a rectangular pool (Experiment 1) or a square pool with walls of different appearances (Experiments 2 and 3). The rats were then released into the pool for a first test trial in the absence of the platform. In Experiment 1, normal rats distinguished the 2 sets of corners in the rectangular pool by their geometric properties, preferring the correct corner and its diagonally opposite partner. Anterior thalamic lesions severely impaired this discrimination. In Experiments 2 and 3, normal rats typically swam directly to the correct corner of the square pool on the first test trial. Rats with anterior thalamic lesions, however, often failed to initially select the correct corner, taking more time to reach that location. Nevertheless, the lesioned rats still showed a subsequent preference for the correct corner. The same lesioned rats also showed no deficits in Experiments 2 and 3 when subsequently trained to swim to the correct corner over repeated trials. The findings show how the anterior thalamic nuclei contribute to multiple aspects of spatial processing. These thalamic nuclei may be required to distinguish relative dimensions (Experiment 1) as well as translate the appearance of spatial cues when viewed for the first time from different perspectives (Experiments 2, 3).

  18. Automatic segmentation and volumetry of multiple sclerosis brain lesions from MR images.

    PubMed

    Jain, Saurabh; Sima, Diana M; Ribbens, Annemie; Cambron, Melissa; Maertens, Anke; Van Hecke, Wim; De Mey, Johan; Barkhof, Frederik; Steenwijk, Martijn D; Daams, Marita; Maes, Frederik; Van Huffel, Sabine; Vrenken, Hugo; Smeets, Dirk

    2015-01-01

    The location and extent of white matter lesions on magnetic resonance imaging (MRI) are important criteria for diagnosis, follow-up and prognosis of multiple sclerosis (MS). Clinical trials have shown that quantitative values, such as lesion volumes, are meaningful in MS prognosis. Manual lesion delineation for the segmentation of lesions is, however, time-consuming and suffers from observer variability. In this paper, we propose MSmetrix, an accurate and reliable automatic method for lesion segmentation based on MRI, independent of scanner or acquisition protocol and without requiring any training data. In MSmetrix, 3D T1-weighted and FLAIR MR images are used in a probabilistic model to detect white matter (WM) lesions as an outlier to normal brain while segmenting the brain tissue into grey matter, WM and cerebrospinal fluid. The actual lesion segmentation is performed based on prior knowledge about the location (within WM) and the appearance (hyperintense on FLAIR) of lesions. The accuracy of MSmetrix is evaluated by comparing its output with expert reference segmentations of 20 MRI datasets of MS patients. Spatial overlap (Dice) between the MSmetrix and the expert lesion segmentation is 0.67 ± 0.11. The intraclass correlation coefficient (ICC) equals 0.8 indicating a good volumetric agreement between the MSmetrix and expert labelling. The reproducibility of MSmetrix' lesion volumes is evaluated based on 10 MS patients, scanned twice with a short interval on three different scanners. The agreement between the first and the second scan on each scanner is evaluated through the spatial overlap and absolute lesion volume difference between them. The spatial overlap was 0.69 ± 0.14 and absolute total lesion volume difference between the two scans was 0.54 ± 0.58 ml. Finally, the accuracy and reproducibility of MSmetrix compare favourably with other publicly available MS lesion segmentation algorithms, applied on the same data using default parameter

  19. Peroxiredoxin 1 has an anti-apoptotic role via apoptosis signal-regulating kinase 1 and p38 activation in mouse models with oral precancerous lesions

    PubMed Central

    ZHANG, JIANFEI; JING, XINYING; NIU, WENWEN; ZHANG, MIN; GE, LIHUA; MIAO, CONGCONG; TANG, XIAOFEI

    2016-01-01

    Peroxiredoxin 1 (Prx1) is important in the protection of cells from oxidative damage and the regulation of cell proliferation and apoptosis. Prx1 is overexpressed in oral precancerous lesions of oral leukoplakia (OLK) and oral cancer; however, the association between Prx1 expression and OLK pathogenesis remains unknown. The present study investigated the role of Prx1 and its molecular mechanisms in oxidative stress-induced apoptosis during the pathogenesis of OLK. Wild-type and Prx1 knockout mice were treated with 50 µg/ml 4-nitroquinoline-1-oxide (4NQO) or 4NQO + H2O2 for 16 weeks to establish mouse models with tongue precancerous lesions. Apoptotic cells were detected using terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. The expression of Prx1, apoptosis signal-regulating kinase 1 (ASK1), phosphor-ASK1, p38 and phosphor-p38 was analyzed using immunohistochemical staining, and their mRNA expression levels were evaluated by reverse transcription quantitative polymerase chain reaction. The present results demonstrated that 4NQO or 4NQO + H2O2 induced the development of tongue precancerous lesions in Prx1 knockout and wild-type mice. Prx1 was overexpressed in tongue precancerous lesions compared with normal tongue mucosa. There was a significant decrease in the degree of moderate or severe epithelial dysplasia, and mild epithelial dysplasia was clearly elevated, in Prx1 knockout mice treated with 4NQO + H2O2 compared with wild-type mice treated with 4NQO + H2O2. Prx1 suppressed apoptosis and upregulated phosphor-ASK1 and phosphor-p38 expression in tongue precancerous lesions. The present results suggest that Prx1 suppresses oxidative stress-induced apoptosis via the ASK1/p38 signalling pathway in mouse tongue precancerous lesions. In conclusion, Prx1 and H2O2 have a coordination role in promoting the progression of tongue precancerous mucosa lesions. The present findings provide novel insight into Prx1 function and the mechanisms of Prx1 in OLK

  20. In situ measurements of activated iodine compounds (ICl, HOI) and molecular iodine in the marine boundary layer by a coupled diffusion denuder system combined with GC-MS

    NASA Astrophysics Data System (ADS)

    Huang, R.-J.; Hoffmann, T.

    2009-04-01

    Recently the impact of iodine on atmospheric chemistry received increasing attention and became a growing active research field [1,2]. Numerous tropospheric filed measurements and modeling studies have been realized [1]; however, a number of uncertainties about the source, sinks, kinetic parameters and the recycling of iodine remain, and the identification and quantification of certain key species (e.g., interhalogens) are still a challenging analytical problem. In this present work we report a coupled denuder system which consists of a 1,3,5-trimethoxybenzene (1,3,5-TMB)-coated cylindrical tube as front-denuder connected upstream of an α-cyclodextrin/129I- (α-CD/129I-)-coated tube for the separation and quantitative collection gaseous activated iodine compounds (ICl, HOI) and molecular iodine (I2) in combination with a gas chromatography-mass spectrometry (GC-MS) method. Detection limits were achieved at sub parts-per-trillion-by-volume (sub-pptv) level. In addition, the analytical system has been applied in field measurements at 3 sites at the west coast of Ireland, (1 sampling site at the Mace Head Atmospheric Research Station (MHARS, 53.25o N, 9.80o W) and 2 sampling sites at Mweenish bay (53.32o N, 9.73o W)), in August-September 2007. The concentrations of both AIC and I2 were found in the pptv-range in most cases. I2 data obtained by the present method were compared with that measured by differential optical absorption spectroscopy (DOAS) technique. Details about diurnal variation of the atmospheric concentrations of both AIC and I2 linked to the meteorological profiles and to other trace gases will be presented. References [1] von Glasow, R.; Crutzen P. J. In Treatise on Geochemistry Update 1; Holland H. D.; Turekian K. K., Ed.; Eleviser: Amsterdam, 2007; vol. 4.02, pp 1-67. [2] Saiz-Lopez, A.; Mahajan, A. S.; Salmon, R. A. Bauguitte, S. J.-B.; Jones, A. E.; Roscoe, H. K.; Plane, J. M. C. Science 317 (2007) 348-351.

  1. Skin lesion of blastomycosis

    MedlinePlus

    ... in: Africa Canada Central and southeastern United States India Israel Saudi Arabia A person gets infected by ... is diagnosed by identifying the fungus in a culture taken from a skin lesion. This usually requires ...

  2. Accuracy of frozen section diagnosis of parotid lesions.

    PubMed

    Miller, R H; Calcaterra, T C; Paglia, D E

    1979-01-01

    The accuracy of frozen section diagnosis was analyzed in a review of 132 parotid lesions. Of 107 benign lesions, 93% were correctly diagnosed on frozen section analysis, but of 25 malignant lesions, only 9 frozen sections were accurately interpreted. This study points out the difficulty encountered in using the frozen section technique when dealing with malignant parotid lesions and the importance of the surgeon's active participation in the analysis.

  3. Acute nontraumatic liver lesions.

    PubMed

    Caremani, Marcello; Tacconi, Danilo; Lapini, Laura

    2013-11-26

    The principal conditions requiring emergency/urgent intervention in patients with nontraumatic liver lesions are hemorrhage (with or without tumor rupture), rupture of hydatid cysts (with or without infection), complications arising from liver abscesses or congenital liver cysts, rupture related to peliosis hepatis, and in rare cases spontaneous hemorrhage. This article examines each of these conditions, its appearance on ultrasound (the first-line imaging method of choice for assessing any urgent nontraumatic liver lesion) and indications for additional imaging studies.

  4. MS/MS Automated Selected Ion Chromatograms

    2005-12-12

    This program can be used to read a LC-MS/MS data file from either a Finnigan ion trap mass spectrometer (.Raw file) or an Agilent Ion Trap mass spectrometer (.MGF and .CDF files) and create a selected ion chromatogram (SIC) for each of the parent ion masses chosen for fragmentation. The largest peak in each SIC is also identified, with reported statistics including peak elution time, height, area, and signal to noise ratio. It creates severalmore » output files, including a base peak intensity (BPI) chromatogram for the survey scan, a BPI for the fragmentation scans, an XML file containing the SIC data for each parent ion, and a "flat file" (ready for import into a database) containing summaries of the SIC data statistics.« less

  5. Multispectral analysis and visualization of multiple sclerosis lesions in MR volumes of the brain

    NASA Astrophysics Data System (ADS)

    Mitchell, Ross; Karlik, Stephen J.; Lee, Donald H.; Fenster, Aaron

    1993-09-01

    MRI is a valuable tool in the diagnosis of multiple sclerosis (MS). Standard MR protocols for imaging MS produce proton density (PD) and T2 weighted images of the same slice in the brain. While these image pairs provide valuable information about MS lesions, they are two dimensional (2-D) while lesions are three dimensional (3-D). Furthermore, the vast amount of data produced in an MR exam for MS makes routine analysis and comparison of the image pairs difficult. Therefore, we have developed a computerized system which employs multi- spectral analysis techniques to allow interactive 3-D analysis of MR data by radiologists and neurologists. We have used our system to classify and analyze four MR exams of a chronic- progressive MS patient taken over an 18 month period. Comparison of volume renderings of classified white matter, grey matter and MS lesions at each exam date provide information about the changes in individual lesions, and total lesion burden. Analysis of the intensity distributions of large MS lesions reveals that they have a wide range of PD/T2 weighted intensities, and some contain a higher PD/longer T2 'core' perhaps corresponding to edema.

  6. Simulation of spread and control of lesions in brain.

    PubMed

    Thamattoor Raman, Krishna Mohan

    2012-01-01

    A simulation model for the spread and control of lesions in the brain is constructed using a planar network (graph) representation for the central nervous system (CNS). The model is inspired by the lesion structures observed in the case of multiple sclerosis (MS), a chronic disease of the CNS. The initial lesion site is at the center of a unit square and spreads outwards based on the success rate in damaging edges (axons) of the network. The damaged edges send out alarm signals which, at appropriate intensity levels, generate programmed cell death. Depending on the extent and timing of the programmed cell death, the lesion may get controlled or aggravated akin to the control of wild fires by burning of peripheral vegetation. The parameter phase space of the model shows smooth transition from uncontrolled situation to controlled situation. The simulations show that the model is capable of generating a wide variety of lesion growth and arrest scenarios. PMID:22319549

  7. Higher Education Moderates the Effect of T2 Lesion Load and Third Ventricle Width on Cognition in Multiple Sclerosis

    PubMed Central

    Pinter, Daniela; Sumowski, James; DeLuca, John; Fazekas, Franz; Pichler, Alexander; Khalil, Michael; Langkammer, Christian; Fuchs, Siegrid; Enzinger, Christian

    2014-01-01

    Background Previous work suggested greater intellectual enrichment might moderate the negative impact of brain atrophy on cognition. This awaits confirmation in independent cohorts including investigation of the role of T2-lesion load (T2-LL), which is another important determinant of cognition in MS. We here thus aimed to test this cognitive reserve hypothesis by investigating whether educational attainment (EA) moderates the negative effects of both brain atrophy and T2-LL on cognitive function in a large sample of MS patients. Methods 137 patients participated in the study. Cognition was assessed by the “Brief Repeatable Battery of Neuropsychological Tests.” T2-LL, normalized brain volume (global volume loss) and third ventricle width (regional volume loss) served as MRI markers. Results Both T2-LL and atrophy predicted worse cognition, with a stronger effect of T2-LL. Higher EA (as assessed by years of education) also predicted better cognition. Interactions showed that the negative effects of T2-LL and regional brain atrophy were moderated by EA. Conclusions In a cohort with different stages of MS, higher EA attenuated the negative effects of white matter lesion burden and third ventricle width (suggestive of thalamic atrophy) on cognitive performance. Actively enhancing cognitive reserve might thus be a means to reduce or prevent cognitive problems in MS in parallel to disease modifying drugs. PMID:24475309

  8. Annotation of glycomics MS and MS/MS spectra using the GlycoWorkbench software tool.

    PubMed

    Damerell, David; Ceroni, Alessio; Maass, Kai; Ranzinger, René; Dell, Anne; Haslam, Stuart M

    2015-01-01

    The GlycoWorkbench software tool allows users to semiautomatically annotate glycomics MS and MS/MS spectra and MS glycoproteomics spectra. The GlycanBuilder software tool is embedded within GlycoWorkbench allowing users to draw glycan structures and export images of the drawn structures. This chapter demonstrates to users how to draw glycan structures within GlycoWorkbench using the GlycanBuilder software tool. This chapter also demonstrates how to use GlycoWorkbench to import MS and MS/MS glycomics spectra and use the cascading annotation feature to annotate both the MS and MS/MS spectra with a single command.

  9. Bioactivity-Guided Fractionation and GC/MS Fingerprinting of Angelica sinensis and Angelica archangelica Root Components for Antifungal and Mosquito Deterrent Activity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Angelica sinensis and A. archangelica belong to the Umbelliferae and both are used in traditional Chinese medicine to treat gynecological and intestinal disorders. In this study, oils from three different A. sinensis collections and one A. archangelica root were analyzed by GC and GC/MS. The domin...

  10. Site and size of multiple sclerosis lesions predict enhanced or decreased female orgasmic function.

    PubMed

    Winder, Klemens; Seifert, Frank; Koehn, Julia; Deutsch, Martina; Engelhorn, Tobias; Dörfler, Arnd; Lee, De-Hyung; Linker, Ralf A; Hilz, Max J

    2015-12-01

    Neuroimaging identified brain areas involved in female orgasm. In women with multiple sclerosis (MS), associations between orgasmic function and the site and size of MS-related magnetic resonance imaging (MRI) changes are undetermined. This study intended to correlate MS-associated cerebral lesion load and location with clinical scores of female orgasmic function. In 50 women with MS (mean age 37.0 ± 9.9 years), we assessed Female Sexual Function Index (FSFI) scores for orgasmic frequency, difficulty and satisfaction. We determined disease duration, Expanded Disability Status Scale (EDSS) scores, and cerebral MS-lesion load and location using T2-weighed 1.5 T MRIs. We correlated FSFI scores for orgasm with patient age, disease duration, EDSS scores, and cerebral MS-lesion load (Spearman rank correlation; significance: p < 0.05). FSFI scores for orgasm correlated inversely with MS-lesion load in the left temporal periventricular white matter and right middle-inferior occipital area, but directly with MS-lesion load in the right frontal primary motor cortex, left prefrontal/inferior frontal cortex, right amygdala, left temporal middle-inferior and fusiform areas, and midbrain. FSFI scores for orgasm did not correlate with patient age, disease duration and EDSS scores (p > 0.05). In conclusion, our results indicate that MS-lesions in left temporal periventricular and right visual association areas deteriorate orgasmic function. In contrast, direct correlations between frontotemporal or midbrain lesions and higher FSFI scores, indicating enhanced or disinhibited orgasmic function, suggest that these brain regions normally buffer orgasmic responses. Moreover, our results indicate that orgasmic dysfunction in women with MS evolves independently of disease duration and physical disability. PMID:26459094

  11. Effects of hydrothermal alteration on Pb in the active PACMANUS hydrothermal field, ODP Leg 193, Manus Basin, Papua New Guinea: A LA-ICP-MS study

    NASA Astrophysics Data System (ADS)

    Beaudoin, Yannick; Scott, Steven D.; Gorton, Michael P.; Zajacz, Zoltan; Halter, Werner

    2007-09-01

    The conventional model of leaching volcanic rocks as a source of metals in a seafloor hydrothermal systems has been tested by examining the behavior of Pb and other trace elements during hydrothermal alteration. ODP Leg 193 drill sites 1188 (Snowcap) and 1189 (Roman Ruins) on Pual Ridge in the eastern Manus Basin offshore eastern Papua New Guinea provide a unique three-dimensional window into an active back-arc hydrothermal system. We investigate by means of a LA-ICP-MS microbeam technique the capacity of Pb to be leached from a host volcanic rock exposed to various types and intensities of alteration. Our results are in general agreement with previous studies that utilized bulk analytical techniques but provide a more detailed explanation of the processes. Fresh representative dacitic lavas from the Pual Ridge have an average whole rock Pb content of 5.2 ppm, an average interstitial glass Pb content of 5.6 ppm and an average plagioclase Pb content of 1.0 ppm. Altered matrix samples have highly variable Pb values ranging from 0 to 52.4 ppm. High Pb values in altered samples are associated with a low temperature chlorite and clay mineral assemblage, in some cases overprinted by a high temperature (up to 350 °C) silica-rich "bleaching" alteration. Only the most highly altered matrix samples have REE patterns that differ from the fresh Pual Ridge dacite. This may represent either different lava histories or alteration characteristics that have affected normally immobile REEs. Altered samples with the highest Pb values have similar REE patterns to those of the local unaltered lavas. They are compositionally similar to typical Pual Ridge dacites indicating a genetic relationship between the main regional volcanic suite and the subseafloor hydrothermally altered, Pb-enriched material. Relative loss/gain for Pb between the analyzed altered samples and a calculated precursor show a maximum relative gain of 901%. Samples with relative Pb gain from both drill sites are

  12. Atypical idiopathic inflammatory demyelinating lesions: prognostic implications and relation to multiple sclerosis.

    PubMed

    Wallner-Blazek, Mirja; Rovira, Alex; Fillipp, Massimo; Rocca, Mara A; Miller, David H; Schmierer, Klaus; Frederiksen, Jette; Gass, Achim; Gama, Hugo; Tilbery, Charles P; Rocha, Antonio J; Flores, José; Barkhof, Frederik; Seewann, Alexandra; Palace, Jacqueline; Yousry, Tarek; Montalban, Xavier; Enzinger, Christian; Fazekas, Franz

    2013-08-01

    Atypical lesions of a presumably idiopathic inflammatory demyelinating origin present quite variably and may pose diagnostic problems. The subsequent clinical course is also uncertain. We, therefore, wanted to clarify if atypical idiopathic inflammatory demyelinating lesions (AIIDLs) can be classified according to previously suggested radiologic characteristics and how this classification relates to prognosis. Searching the databases of eight tertiary referral centres we identified 90 adult patients (61 women, 29 men; mean age 34 years) with ≥ 1 AIIDL. We collected their demographic, clinical and magnetic resonance imaging data and obtained follow-up (FU) information on 77 of these patients over a mean duration of 4 years. The AIIDLs presented as a single lesion in 72 (80 %) patients and exhibited an infiltrative (n = 35), megacystic (n = 16), Baló (n = 10) or ring-like (n = 16) lesion appearance in 77 (86 %) patients. Additional multiple sclerosis (MS)-typical lesions existed in 48 (53 %) patients. During FU, a further clinical attack occurred rarely (23-35 % of patients) except for patients with ring-like AIIDLs (62 %). Further attacks were also significantly more often in patients with coexisting MS-typical lesions (41 vs. 10 %, p < 0.005). New AIIDLs developed in six (7 %), and new MS-typical lesions in 29 (42 %) patients. Our findings confirm the previously reported subtypes of AIIDLs. Most types confer a relatively low risk of further clinical attacks, except for ring-like lesions and the combination with MS-typical lesions.

  13. Antioxidant and anti-fatigue activities of phenolic extract from the seed coat of Euryale ferox Salisb. and identification of three phenolic compounds by LC-ESI-MS/MS.

    PubMed

    Wu, Chengying; Chen, Rong; Wang, Xin Sheng; Shen, Bei; Yue, Wei; Wu, Qinan

    2013-09-09

    This study investigated the antioxidant potential and anti-fatigue effects of phenolics extracted from the seed coat of Euryale ferox Salisb. The in vitro antioxidant potentials, including scavenging DPPH, hydroxyl radical activities and reducing power were evaluated. Antioxidant status in vivo was analyzed by SOD, CAT, GSH-Px activities and the MDA content in liver and kidneys of D-galactose-induced aging mice. The anti-fatigue effect was evaluated using an exhaustive swimming test, along with the determination of LDH, BUN and HG content. The phenolic extract possessed notable antioxidant effects on DPPH, hydroxyl radical scavenging and reducing power. The mice which received the phenolic extract showed significant increases of SOD, CAT (except for in the kidney), GSH-Px activities, and a decrease of MDA content. The average exhaustive swimming time was obviously prolonged. Meanwhile, increase of LDH content and decrease of BUN content were observed after mice had been swimming for 15 min. The HG storage of mice was improved in the high and middle dose extract groups compared with the normal group. The contents of total phenols and gallic acid of the extract were determined. Three compounds in the extract were identified as 5,7-dihydroxy-2-(3,4,5-trihydroxyphenyl)-chroman-4-one, 5,7,4-trihydroxyflavanone and buddlenol E. These results suggest that the extract of E. ferox is a promising source of natural antioxidants and anti-fatigue material for use in functional foods and medicines.

  14. Antioxidant and anti-fatigue activities of phenolic extract from the seed coat of Euryale ferox Salisb. and identification of three phenolic compounds by LC-ESI-MS/MS.

    PubMed

    Wu, Chengying; Chen, Rong; Wang, Xin Sheng; Shen, Bei; Yue, Wei; Wu, Qinan

    2013-01-01

    This study investigated the antioxidant potential and anti-fatigue effects of phenolics extracted from the seed coat of Euryale ferox Salisb. The in vitro antioxidant potentials, including scavenging DPPH, hydroxyl radical activities and reducing power were evaluated. Antioxidant status in vivo was analyzed by SOD, CAT, GSH-Px activities and the MDA content in liver and kidneys of D-galactose-induced aging mice. The anti-fatigue effect was evaluated using an exhaustive swimming test, along with the determination of LDH, BUN and HG content. The phenolic extract possessed notable antioxidant effects on DPPH, hydroxyl radical scavenging and reducing power. The mice which received the phenolic extract showed significant increases of SOD, CAT (except for in the kidney), GSH-Px activities, and a decrease of MDA content. The average exhaustive swimming time was obviously prolonged. Meanwhile, increase of LDH content and decrease of BUN content were observed after mice had been swimming for 15 min. The HG storage of mice was improved in the high and middle dose extract groups compared with the normal group. The contents of total phenols and gallic acid of the extract were determined. Three compounds in the extract were identified as 5,7-dihydroxy-2-(3,4,5-trihydroxyphenyl)-chroman-4-one, 5,7,4-trihydroxyflavanone and buddlenol E. These results suggest that the extract of E. ferox is a promising source of natural antioxidants and anti-fatigue material for use in functional foods and medicines. PMID:24022762

  15. Managing Progressive MS

    MedlinePlus

    ... MS Society | 8 builders about renovations and home adaptations to support independence. OTs may also evaluate and ... Staying at home will mean making changes. Home adaptations do more than fight fatigue. They offer safety, ...

  16. Living with Advanced MS

    MedlinePlus

    ... Read More Read More Resource Edward M. Dowd Personal Advocate Program The Edward M. Dowd Personal Advocate ... Informed About the Society Vision Careers Leadership Cultural Values Financials News Press Room MS Prevalence Charitable Ratings ...

  17. MS Based Metabonomics

    SciTech Connect

    Want, Elizabeth J.; Metz, Thomas O.

    2010-03-01

    Metabonomics is the latest and least mature of the systems biology triad, which also includes genomics and proteomics, and has its origins in the early orthomolecular medicine work pioneered by Linus Pauling and Arthur Robinson. It was defined by Nicholson and colleagues in 1999 as the quantitative measurement of perturbations in the metabolite complement of an integrated biological system in response to internal or external stimuli, and is often used today to describe many non-global types of metabolite analyses. Applications of metabonomics are extensive and include toxicology, nutrition, pharmaceutical research and development, physiological monitoring and disease diagnosis. For example, blood samples from millions of neonates are tested routinely by mass spectrometry (MS) as a diagnostic tool for inborn errors of metabolism. The metabonome encompasses a wide range of structurally diverse metabolites; therefore, no single analytical platform will be sufficient. Specialized sample preparation and detection techniques are required, and advances in NMR and MS technologies have led to enhanced metabonome coverage, which in turn demands improved data analysis approaches. The role of MS in metabonomics is still evolving as instrumentation and software becomes more sophisticated and as researchers realize the strengths and limitations of current technology. MS offers a wide dynamic range, high sensitivity, and reproducible, quantitative analysis. These attributes are essential for addressing the challenges of metabonomics, as the range of metabolite concentrations easily exceeds nine orders of magnitude in biofluids, and the diversity of molecular species ranges from simple amino and organic acids to lipids and complex carbohydrates. Additional challenges arise in generating a comprehensive metabolite profile, downstream data processing and analysis, and structural characterization of important metabolites. A typical workflow of MS-based metabonomics is shown in Figure

  18. Meniscal Ramp Lesions

    PubMed Central

    Chahla, Jorge; Dean, Chase S.; Moatshe, Gilbert; Mitchell, Justin J.; Cram, Tyler R.; Yacuzzi, Carlos; LaPrade, Robert F.

    2016-01-01

    Meniscal ramp lesions are more frequently associated with anterior cruciate ligament (ACL) injuries than previously recognized. Some authors suggest that this entity results from disruption of the meniscotibial ligaments of the posterior horn of the medial meniscus, whereas others support the idea that it is created by a tear of the peripheral attachment of the posterior horn of the medial meniscus. Magnetic resonance imaging (MRI) scans have been reported to have a low sensitivity, and consequently, ramp lesions often go undiagnosed. Therefore, to rule out a ramp lesion, an arthroscopic evaluation with probing of the posterior horn of the medial meniscus should be performed. Several treatment options have been reported, including nonsurgical management, inside-out meniscal repair, or all-inside meniscal repair. In cases of isolated ramp lesions, a standard meniscal repair rehabilitation protocol should be followed. However, when a concomitant ACL reconstruction (ACLR) is performed, the rehabilitation should follow the designated ACLR postoperative protocol. The purpose of this article was to review the current literature regarding meniscal ramp lesions and summarize the pertinent anatomy, biomechanics, diagnostic strategies, recommended treatment options, and postoperative protocol. PMID:27504467

  19. Monitoring pigmented skin lesions

    NASA Astrophysics Data System (ADS)

    Wallace, Vincent P.; Bamber, Jeffery C.; Ott, Robert J.; Crawford, Diane C.; Mortimer, Peter S.

    2002-06-01

    The rising incidence of skin cancer has led to an increase in the number of patients with skin lesions that require diagnosis, mostly using subjective visual examination. Successful treatment depends on early diagnosis. Unfortunately diagnostic accuracy, even by experts, can be as low as 56%; therefore, an accurate, objective diagnostic aid is greatly needed. Reflectance characteristics of pigmented skin lesions were documented to evaluate their diagnostic potential. Reflectance spectra in the wavelength range 320-1100nm were obtained from 260 lesions. Differences between spectra from benign and malignant lesions were utilized by extracting features with the best discriminating power. Discrimination was evaluated using two techniques: multivariate statistical analysis and artificial neural networks, using histology as the standard. Each technique was tested in a blind study and assessed in terms of its ability to diagnose new cases and compared to the clinical diagnosis. The artificial neural network achieved the best diagnostic performance for discriminating between malignant melanoma and benign nevi, having a sensitivity of 100% and a specificity of 65%. Utilization of visible and infrared techniques for monitoring skin lesions has lead to improvements in diagnostic accuracy. We conclude that these techniques are worthy of further development and evaluation in clinical practice as a screening tool.

  20. IMS - MS Data Extractor

    SciTech Connect

    2015-10-20

    An automated drift time extraction and computed associated collision cross section software tool for small molecule analysis with ion mobility spectrometry-mass spectrometry (IMS-MS). The software automatically extracts drift times and computes associated collision cross sections for small molecules analyzed using ion mobility spectrometry-mass spectrometry (IMS-MS) based on a target list of expected ions provided by the user.

  1. Diode laser treatment and clinical management of multiple oral lesions in patients with hereditary haemorrhagic telangiectasia.

    PubMed

    Favia, G; Tempesta, A; Limongelli, L; Suppressa, P; Sabbà, C; Maiorano, E

    2016-05-01

    Hereditary haemorrhagic telangiectasia (HHT) is rare, and characterised by vascular dysplasia that leads to various symptoms including visceral arteriovenous malformations and mucocutaneous telangiectatic lesions. Our aim was to describe the clinical features and options for the treatment of multiple oral lesions, and to illustrate the efficacy of the diode laser in the treatment of early (<2mm) and advanced lesions (2mm or more). We report 24 patients with 1200 oral telangiectatic lesions, which were often associated with regular bleeding (from monthly to daily), superinfection, pain, and swelling, and treated with multiple sessions of laser according to the number and size of the lesions. Early lesions were treated with a single laser impulse in ultrapulsed mode, and advanced lesions with repeated laser impulses in pulsed mode (t-on 200ms/t-off 500ms), at a power of 8W. Early lesions healed completely after laser photocoagulation with no operative or postoperative complications, while advanced lesions improved with a remarkable reduction in size but more discomfort. Protective occlusal plates were sometimes used to reduce the incidence of new lesions caused by dental trauma. The treatment of oral telangiectatic lesions is still being debated, and it is important to improve quality of life for patients. Diode laser surgery could be an effective treatment for oral lesions in those with hereditary haemorrhagic telangiectasia.

  2. Simultaneous determination of bupropion, metroprolol, midazolam, phenacetin, omeprazole and tolbutamide in rat plasma by UPLC-MS/MS and its application to cytochrome P450 activity study in rats.

    PubMed

    Ma, Jianshe; Wang, Shuanghu; Zhang, Meiling; Zhang, Qingwei; Zhou, Yunfang; Lin, Chongliang; Lin, Guanyang; Wang, Xianqin

    2015-08-01

    A specific ultra-performance liquid chromatography tandem mass spectrometry method is described for the simultaneous determination of bupropion, metroprolol, midazolam, phenacetin, omeprazole and tolbutamide in rat plasma with diazepam as internal standard, which are the six probe drugs of the six cytochrome P450 isoforms CYP2B6, CYP2D6, CYP3A4, CYP1A2, CYP2C19 and CYP2C9. Plasma samples were protein precipitated with acetonitrile. The chromatographic separation was achieved using a UPLC® BEH C18 column (2.1 × 100 mm, 1.7 µm). The mobile phase consisted of acetonitrile and water (containing 0.1% formic acid) with gradient elution. The triple quadrupole mass spectrometric detection was operated by multiple reaction monitoring in positive electrospray ionization. The precisions were <13%, and the accuracy ranged from 93.3 to 110.4%. The extraction efficiency was >90.5%, and the matrix effects ranged from 84.3 to 114.2%. The calibration curves in plasma were linear in the range of 2-2000 ng/mL, with correlation coefficient (r(2) ) >0.995. The method was successfully applied to pharmacokinetic studies of the six probe drugs of the six CYP450 isoforms and used to evaluate the effects of erlotinib on the activities of CYP2B6, CYP2D6, CYP3A4, CYP1A2, CYP2C19 and CYP2C9 in rats. Erlotinib may inhibit the activity of CYP2B6 and CYP3A4, and may induce CYP2C9 of rats.

  3. Intraventricular mass lesions

    SciTech Connect

    Morrison, G.; Sobel, D.F.; Kelley, W.M.; Norman, D.

    1984-11-01

    Determining the precise etiology of an intraventricular mass can be a difficult diagnostic problem. CT and angiographic findings were reviewed in a series of 73 patients who had intraventricular masses. The histologic diagnosis can be suggested preoperatively by an analysis of the frequency of lesions occurring at a given ventricular location, lesion density before and after administration of contrast material, age, and sex of the patient, morphologic appearance of the mass, and presence or absence of hydrocephalus. Angiography is useful when meningioma, choroid plexus papilloma and carcinoma, or arteriovenous malformation are considered.

  4. Bioactivity-guided fractionation and GC/MS fingerprinting of Angelica sinensis and Angelica archangelica root components for antifungal and mosquito deterrent activity.

    PubMed

    Wedge, David E; Klun, Jerome A; Tabanca, Nurhayat; Demirci, Betul; Ozek, Temel; Baser, Kemal Husnu Can; Liu, Zhijun; Zhang, Sui; Cantrell, Charles L; Zhang, Jian

    2009-01-28

    Bioassay-guided fractionation of the chloroform extract from the roots of Angelica sinensis led to isolation and characterization of (Z)-ligustilide using direct-bioautography with Colletotrichum species. The structure of (Z)-ligustilide was confirmed by (1)H and (13)C NMR spectroscopy and GC/MS. (Z)-Ligustilide deterred the biting of two mosquito species more effectively than DEET. Three different A. sinensis accessions and one Angelica archangelica root oil were evauated by GC and GC/MS, and the dominant component in A. sinensis was 61-69% (Z)-ligustilide. Two other prominent compounds in A. sinensis oils were 5.7-9.8% (E)-3-butylidene phthalide and 1.5-2.3% (Z)-3-butylidene phthalide. The main constituents that comprised A. archangelica oil were monoterpene hydrocarbons such as 24.5% alpha-pinene, 13.8% delta-3-carene, 10.1% beta-phellandrene, 8.8% p-cymene, 8.4% limonene, and 6.3% sabinene. Phthalides and monoterpene hydrocarbons were determined to be good systematic markers or chemical fingerprints for A. sinensis and A. archangelica root oils. Chemical fingerprinting by GC/MS of A. sinensis also confirmed the misidentification of one A. archangelica sample sold in the Chinese market. PMID:19113871

  5. Progressive-Relapsing MS (PRMS)

    MedlinePlus

    ... the disease process in MS and in MRI technology. Individuals who were previously diagnosed with progressive-relapsing MS would now be ... The National MS Society is Here to Help Need More Information? We ...

  6. αβ T-cell receptors from multiple sclerosis brain lesions show MAIT cell–related features

    PubMed Central

    Held, Kathrin; Bhonsle-Deeng, Latika; Siewert, Katherina; Sato, Wakiro; Beltrán, Eduardo; Schmidt, Stephan; Rühl, Geraldine; Ng, Judy K.M.; Engerer, Peter; Moser, Markus; Klinkert, Wolfgang E.F.; Babbe, Holger; Misgeld, Thomas; Wekerle, Hartmut; Laplaud, David-Axel; Hohlfeld, Reinhard

    2015-01-01

    Objectives: To characterize phenotypes of T cells that accumulated in multiple sclerosis (MS) lesions, to compare the lesional T-cell receptor (TCR) repertoire of T-cell subsets to peripheral blood, and to identify paired α and β chains from single CD8+ T cells from an index patient who we followed for 18 years. Methods: We combined immunohistochemistry, laser microdissection, and single-cell multiplex PCR to characterize T-cell subtypes and identify paired TCRα and TCRβ chains from individual brain-infiltrating T cells in frozen brain sections. The lesional and peripheral TCR repertoires were analyzed by pyrosequencing. Results: We found that a TCR Vβ1+ T-cell population that was strikingly expanded in active brain lesions at clinical onset comprises several subclones expressing distinct yet closely related Vα7.2+ α chains, including a canonical Vα7.2-Jα33 chain of mucosal-associated invariant T (MAIT) cells. Three other α chains bear striking similarities in their antigen-recognizing, hypervariable complementarity determining region 3. Longitudinal repertoire studies revealed that the TCR chains that were massively expanded in brain at onset persisted for several years in blood or CSF but subsequently disappeared except for the canonical Vα7.2+ MAIT cell and a few other TCR sequences that were still detectable in blood after 18 years. Conclusions: Our observation that a massively expanded TCR Vβ1-Jβ2.3 chain paired with distinct yet closely related canonical or atypical MAIT cell–related α chains strongly points to an antigen-driven process in early active MS brain lesions. PMID:25977934

  7. Magnetic resonance imaging of liver lesions: exceptions and atypical lesions.

    PubMed

    van den Bos, Indra C; Hussain, Shahid M; de Man, Robert A; Zondervan, Pieter E; Ijzermans, Jan N M; Preda, A; Krestin, Gabriel P

    2008-01-01

    On state-of-the-art magnetic resonance imaging, most lesions can be detected and characterized with confidence according to well-known criteria. However, atypical characteristics in some common lesions and the incidental encounter with rare lesions may pose diagnostic difficulties. In this article, six challenging hepatic lesions will be discussed and evaluated on the most important magnetic resonance imaging sequences, with histological correlation when available. In addition, the background information concerning these lesions will be described based on the most recent available literature. By reading this article, the reader will be able to (1) categorize the lesion in solid and fluid-containing lesions, based on the T2 signal intensity; and (2) define the benign or malignant nature of the lesion, in relation to the signal intensity and dynamic enhancement pattern, despite the presence of atypical characteristics of some lesions. PMID:18436109

  8. Robust detection of multiple sclerosis lesions from intensity-normalized multi-channel MRI

    NASA Astrophysics Data System (ADS)

    Karpate, Yogesh; Commowick, Olivier; Barillot, Christian

    2015-03-01

    Multiple sclerosis (MS) is a disease with heterogeneous evolution among the patients. Quantitative analysis of longitudinal Magnetic Resonance Images (MRI) provides a spatial analysis of the brain tissues which may lead to the discovery of biomarkers of disease evolution. Better understanding of the disease will lead to a better discovery of pathogenic mechanisms, allowing for patient-adapted therapeutic strategies. To characterize MS lesions, we propose a novel paradigm to detect white matter lesions based on a statistical framework. It aims at studying the benefits of using multi-channel MRI to detect statistically significant differences between each individual MS patient and a database of control subjects. This framework consists in two components. First, intensity standardization is conducted to minimize the inter-subject intensity difference arising from variability of the acquisition process and different scanners. The intensity normalization maps parameters obtained using a robust Gaussian Mixture Model (GMM) estimation not affected by the presence of MS lesions. The second part studies the comparison of multi-channel MRI of MS patients with respect to an atlas built from the control subjects, thereby allowing us to look for differences in normal appearing white matter, in and around the lesions of each patient. Experimental results demonstrate that our technique accurately detects significant differences in lesions consequently improving the results of MS lesion detection.

  9. Automatic iterative segmentation of multiple sclerosis lesions using Student's t mixture models and probabilistic anatomical atlases in FLAIR images.

    PubMed

    Freire, Paulo G L; Ferrari, Ricardo J

    2016-06-01

    Multiple sclerosis (MS) is a demyelinating autoimmune disease that attacks the central nervous system (CNS) and affects more than 2 million people worldwide. The segmentation of MS lesions in magnetic resonance imaging (MRI) is a very important task to assess how a patient is responding to treatment and how the disease is progressing. Computational approaches have been proposed over the years to segment MS lesions and reduce the amount of time spent on manual delineation and inter- and intra-rater variability and bias. However, fully-automatic segmentation of MS lesions still remains an open problem. In this work, we propose an iterative approach using Student's t mixture models and probabilistic anatomical atlases to automatically segment MS lesions in Fluid Attenuated Inversion Recovery (FLAIR) images. Our technique resembles a refinement approach by iteratively segmenting brain tissues into smaller classes until MS lesions are grouped as the most hyperintense one. To validate our technique we used 21 clinical images from the 2015 Longitudinal Multiple Sclerosis Lesion Segmentation Challenge dataset. Evaluation using Dice Similarity Coefficient (DSC), True Positive Ratio (TPR), False Positive Ratio (FPR), Volume Difference (VD) and Pearson's r coefficient shows that our technique has a good spatial and volumetric agreement with raters' manual delineations. Also, a comparison between our proposal and the state-of-the-art shows that our technique is comparable and, in some cases, better than some approaches, thus being a viable alternative for automatic MS lesion segmentation in MRI. PMID:27058437

  10. Automatic iterative segmentation of multiple sclerosis lesions using Student's t mixture models and probabilistic anatomical atlases in FLAIR images.

    PubMed

    Freire, Paulo G L; Ferrari, Ricardo J

    2016-06-01

    Multiple sclerosis (MS) is a demyelinating autoimmune disease that attacks the central nervous system (CNS) and affects more than 2 million people worldwide. The segmentation of MS lesions in magnetic resonance imaging (MRI) is a very important task to assess how a patient is responding to treatment and how the disease is progressing. Computational approaches have been proposed over the years to segment MS lesions and reduce the amount of time spent on manual delineation and inter- and intra-rater variability and bias. However, fully-automatic segmentation of MS lesions still remains an open problem. In this work, we propose an iterative approach using Student's t mixture models and probabilistic anatomical atlases to automatically segment MS lesions in Fluid Attenuated Inversion Recovery (FLAIR) images. Our technique resembles a refinement approach by iteratively segmenting brain tissues into smaller classes until MS lesions are grouped as the most hyperintense one. To validate our technique we used 21 clinical images from the 2015 Longitudinal Multiple Sclerosis Lesion Segmentation Challenge dataset. Evaluation using Dice Similarity Coefficient (DSC), True Positive Ratio (TPR), False Positive Ratio (FPR), Volume Difference (VD) and Pearson's r coefficient shows that our technique has a good spatial and volumetric agreement with raters' manual delineations. Also, a comparison between our proposal and the state-of-the-art shows that our technique is comparable and, in some cases, better than some approaches, thus being a viable alternative for automatic MS lesion segmentation in MRI.

  11. [Managing focal incidental renal lesions].

    PubMed

    Nicolau, C; Paño, B; Sebastià, C

    2016-01-01

    Incidental renal lesions are relatively common in daily radiological practice. It is important to know the different diagnostic possibilities for incidentally detected lesions, depending on whether they are cystic or solid. The management of cystic lesions is guided by the Bosniak classification. In solid lesions, the goal is to differentiate between renal cancer and benign tumors such as fat-poor angiomyolipoma and oncocytoma. Radiologists need to know the recommendations for the management of these lesions and the usefulness of the different imaging techniques and interventional procedures in function of the characteristics of the incidental lesion and the patient's life expectancy.

  12. Automated SPME-GC-MS monitoring of headspace metabolomic responses of E. coli to biologically active components extracted by the coating.

    PubMed

    Hossain, S M Zakir; Bojko, Barbara; Pawliszyn, Janusz

    2013-05-01

    Monitoring extracellular metabolites of bacteria is very useful for not only metabolomics research but also for assessment of the effects of various chemicals, including antimicrobial agents and drugs. Herein, we describe the automated headspace solid-phase microextraction (HS-SPME) method coupled with gas chromatography-mass spectrometry (GC-MS) for the qualitative as well as semi-quantitative determination of metabolic responses of Escherichia coli to an antimicrobial agent, cinnamaldehyde. The minimum inhibitory concentration of cinnamaldehyde was calculated to be 2 g L(-1). We found that cinnamaldehyde was an important factor influencing the metabolic profile and growth process. A higher number of metabolites were observed during the mid-logarithmic growth phase. The metabolite variations (types and concentrations) induced by cinnamaldehyde were dependent on both cell density and the dose of cinnamaldehyde. Simultaneously, 25 different metabolites were separated and detected (e.g., indole, alkane, alcohol, organic acids, esters, etc.) in headspace of complex biological samples due to intermittent addition of high dose of cinnamaldehyde. The study was done using an automated system, thereby minimizing manual workup and indicating the potential of the method for high-throughput analysis. These findings enhanced the understanding of the metabolic responses of E. coli to cinnamaldehyde shock effect and demonstrated the effectiveness of the SPME-GC-MS based metabolomics approach to study such a complex biological system. PMID:23601279

  13. ICP-MS Workshop

    SciTech Connect

    Carman, April J.; Eiden, Gregory C.

    2014-11-01

    This is a short document that explains the materials that will be transmitted to LLNL and DNN HQ regarding the ICP-MS Workshop held at PNNL June 17-19th. The goal of the information is to pass on to LLNL information regarding the planning and preparations for the Workshop at PNNL in preparation of the SIMS workshop at LLNL.

  14. DIR-visible grey matter lesions and atrophy in multiple sclerosis: partners in crime?

    PubMed Central

    van de Pavert, Steven H P; Muhlert, Nils; Sethi, Varun; Wheeler-Kingshott, Claudia A M; Geurts, Jeroen J G; Ron, Maria; Yousry, Tarek A; Thompson, Alan J; Miller, David H; Chard, Declan T; Ciccarelli, Olga

    2016-01-01

    Background The extent and clinical relevance of grey matter (GM) pathology in multiple sclerosis (MS) are increasingly recognised. GM pathology may present as focal lesions, which can be visualised using double inversion recovery (DIR) MRI, or as diffuse pathology, which can manifest as atrophy. It is, however, unclear whether the diffuse atrophy centres on focal lesions. This study aimed to determine if GM lesions and GM atrophy colocalise, and to assess their independent relationship with motor and cognitive deficits in MS. Methods Eighty people with MS and 30 healthy controls underwent brain volumetric T1-weighted and DIR MRI at 3 T, and had a comprehensive neurological and cognitive assessment. Probability mapping of GM lesions marked on the DIR scans and voxel- based morphometry (assessing GM atrophy) were carried out. The associations of GM lesion load and GM volume with clinical scores were tested. Results DIR-visible GM lesions were most commonly found in the right cerebellum and most apparent in patients with primary progressive MS. Deep GM structures appeared largely free from lesions, but showed considerable atrophy, particularly in the thalamus, caudate, pallidum and putamen, and this was most apparent in secondary progressive patients with MS. Very little co-localisation of GM atrophy and lesions was seen, and this was generally confined to the cerebellum and postcentral gyrus. In both regions, GM lesions and volume independently correlated with physical disability and cognitive performance. Conclusions DIR-detectable GM lesions and GM atrophy do not significantly overlap in the brain but, when they do, they independently contribute to clinical disability. PMID:25926483

  15. Novel lesion detection aids.

    PubMed

    Neuhaus, K W; Longbottom, C; Ellwood, R; Lussi, A

    2009-01-01

    Several non-invasive and novel aids for the detection of (and in some cases monitoring of) caries lesions have been introduced in the field of 'caries diagnostics' over the last 15 years. This chapter focusses on those available to dentists at the time of writing; continuing research is bound to lead to further developments in the coming years. Laser fluorescence is based on measurements of back-scattered fluorescence of a 655-nm light source. It enhances occlusal and (potentially) approximal lesion detection and enables semi-quantitative caries monitoring. Systematic reviews have identified false-positive results as a limitation. Quantitative light-induced fluorescence is another sensitive method to quantitatively detect and measure mineral loss both in enamel and some dentine lesions; again, the trade-offs with lower specificity when compared with clinical visual detection must be considered. Subtraction radiography is based on the principle of digitally superimposing two radiographs with exactly the same projection geometry. This method is applicable for approximal surfaces and occlusal caries involving dentine but is not yet widely available. Electrical caries measurements gather either site-specific or surface-specific information of teeth and tooth structure. Fixed-frequency devices perform best for occlusal dentine caries but the method has also shown promise for lesions in enamel and other tooth surfaces with multi-frequency approaches. All methods require further research and further validation in well-designed clinical trials. In the future, they could have useful applications in clinical practice as part of a personalized, comprehensive caries management system. PMID:19494675

  16. [HPV-associated cutaneous lesions].

    PubMed

    Kiyofumi, Egawa

    2008-12-01

    More than 100 HPV genotypes are presently distinguished by comparing the DNA sequence of the L1 ORF of each HPV. Two important aspects of the nature of this group of heterogeneous viruses are the way in which specific HPV genotypes are associated with distinct clinical and histological morphologies and the way specific HPV genotypes affect distinct anatomical sites. The former is best evidenced by the HPV type specific cytopathic or cytopathogenic effect (CPE), whereas the latter is suggested by the marked preference of each HPV genotype for specific tissues and sites. Recent studies have also suggested that specific HPV genotypes may target epithelial stem cells at specific anatomical sites. HPV type-specific CPE is the central schema when we analyze and understand the HPV-associated diseases. The concept was suggested by the characterization of distinct HPVs from different types of warts: HPV 2/27/57 from common warts, HPV 3/10/28 from flat warts, HPV 6/11 from condyloma acuminatum, and HPV 5/8 from lesions of epidermodysplasia verruciformis (EV). In this paper, I summarize recent advances in HPV study field, especially on HPV-associated cutaneous lesions. These include inclusion warts, HPV-associated epidermoid cysts, HPV type specific activation of melanogenesis, a double infection with HPV 1 and HPV 63 within a single cell, primary target cells and life cycle of the virus, and the identification of novel genes that are associated EV. The HPV-associated cutaneous lesions thus pose important problems to be resolved in virology and human pathology. PMID:19374195

  17. Knowledge guided information fusion for segmentation of multiple sclerosis lesions in MRI images

    NASA Astrophysics Data System (ADS)

    Zhu, Chaozhe; Jiang, Tianzi

    2003-05-01

    In this work, T1-, T2- and PD-weighted MR images of multiple sclerosis (MS) patients, providing information on the properties of tissues from different aspects, are treated as three independent information sources for the detection and segmentation of MS lesions. Based on information fusion theory, a knowledge guided information fusion framework is proposed to accomplish 3-D segmentation of MS lesions. This framework consists of three parts: (1) information extraction, (2) information fusion, and (3) decision. Information provided by different spectral images is extracted and modeled separately in each spectrum using fuzzy sets, aiming at managing the uncertainty and ambiguity in the images due to noise and partial volume effect. In the second part, the possible fuzzy map of MS lesions in each spectral image is constructed from the extracted information under the guidance of experts' knowledge, and then the final fuzzy map of MS lesions is constructed through the fusion of the fuzzy maps obtained from different spectrum. Finally, 3-D segmentation of MS lesions is derived from the final fuzzy map. Experimental results show that this method is fast and accurate.

  18. Effects of the uncompetitive NMDA receptor antagonist memantine on spatial memory in medial septal lesioned rats.

    PubMed

    Dashniani, M; Burjanadze, M; Beselia, G; Chkhikvishvili, N; Kruashvili, L

    2011-12-01

    These experiments examined the effects of acute administration of memantine (2.5 or 5 mg/kg) or saline on spatial memory and learning process within single sessions, on place versions of food-rewarded maze in MS electrolytic lesioned and sham-lesioned rats. Sham-lesioned rats trained in the place task learned more rapidly than did MS electrolytic lesioned rats. This fact certifies for obvious deficit of the place learning performance strategy in the MS-lesioned rats. The results indicate that the drug-treated (5 mg/kg memantine) sham-lesioned rats exhibited significantly impaired performance relative to the saline controls in terms of trials-to-criterion (P<0.05). 2.5 mg/kg memantine administered 30 min before behavioral testing, did not affect performance in place learning task. 2.5 mg/kg and 5 mg/kg memantine administered before behavioral testing, did not improve performance in place learning task in MS electrolytic lesioned rats. Our experimental data support the interpretation that memantine does not produce intolerable side effects in human AD patients because it is being used at doses that are below the threshold for interacting with NMDA receptors.

  19. Rapid screening and identification of compounds with DNA-binding activity from Folium Citri Reticulatae using on-line HPLC-DAD-MS(n) coupled with a post column fluorescence detection system.

    PubMed

    Fu, Qingrong; Zhang, Cangman; Lin, Zongtao; Sun, Hongyang; Liang, Yi; Jiang, Haixiu; Song, Zhiling; Wang, Hong; Chen, Shizhong

    2016-02-01

    To study the interactions between natural compounds and deoxyribonucleic acid (DNA), a method has been established combining a high-performance liquid chromatography-diode array detector-multi-stage mass spectrometer with a fluorescence detector (HPLC-DAD-MS(n)-FLD). The FLD was used to monitor fluorescence intensity of the ethidium bromide-DNA (EB-DNA) complex when a compound separated by HPLC was introduced. This novel method was used to simultaneously obtain the HPLC fingerprint, UV spectra, MS(n) fragments and DNA-binding activity profile of various components in Folium Citri Reticulatae. As a result, 35 compounds were identified, of which 25 were found in the extract of Folium Citri Reticulatae for the first time, and 33 compounds showed DNA-binding activities, with the most active being feruloylhexaric and p-coumaroylhexaric acids. In addition, the precision, stability and reproducibility of this method were validated by two positive controls, quercetin and hesperidin. This new on-line method is accurate, precise and reliable for further high-throughput screening of DNA-binding compounds from food samples and other complex matrices.

  20. NAPS-MS

    PubMed Central

    Gudesblatt, Mark; Kresa-Reahl, Kiren; Brandes, David W.; Sater, Pamela

    2016-01-01

    Background: Patients with multiple sclerosis (MS) have higher rates of fatigue, mood disturbance, and cognitive impairments than healthy populations. Disease-modifying agents may affect sleep. Although patients taking natalizumab often show improvement in fatigue during the first year of therapy, the mechanism behind this effect is unknown. The aim of the NAPS-MS study was to investigate whether natalizumab affected objective measures of sleep as determined by polysomnography (PSG) and multiple sleep latency testing (MSLT) in patients with MS with fatigue or sleepiness initiating therapy. Additional goals were to evaluate changes in measures of fatigue, mood, and cognition and to correlate these measures with objective sleep measures. Methods: Patients underwent PSG and MSLT before their first natalizumab infusion and after their seventh. Patients completed the Modified Fatigue Impact Scale, Fatigue Severity Scale (FSS), Epworth Sleepiness Scale (ESS), and visual analogue scale for fatigue (VAS-F) at their first, fourth, and seventh natalizumab infusions. NeuroTrax cognitive tests and the Hospital Anxiety and Depression Scale (HADS) were performed at the first and seventh natalizumab infusions. Results: Changes in sleep efficiency, wakefulness after sleep onset, and multiple sleep latency from baseline to 6 months of therapy did not reach significance. The FSS, VAS-F, ESS, and HADS scores were significantly improved after 6 months of therapy; cognitive scores were not significantly improved. Conclusions: Although treatment with natalizumab was associated with improvements in fatigue, sleepiness, and mood, changes in objective measures of sleep were not significant. PMID:27551242

  1. Gastroprotective Activity of Violacein Isolated from Chromobacterium violaceum on Indomethacin-Induced Gastric Lesions in Rats: Investigation of Potential Mechanisms of Action

    PubMed Central

    Antonisamy, Paulrayer; Kannan, Ponnusamy; Aravinthan, Adithan; Duraipandiyan, Veeramuthu; Valan Arasu, Mariadhas; Ignacimuthu, Savarimuthu; Abdullah Al-Dhabi, Naif; Kim, Jong-Hoon

    2014-01-01

    Chromobacterium violaceum, Gram-negative bacteria species found in tropical regions of the world, produces a distinct deep violet-colored pigment called violacein. In the present study, we investigated whether violacein can promote a gastroprotective effect and verified the possible mechanisms involved in this action. For this study, an indomethacin-induced gastric ulcer rat model was used. The roles of biomolecules such as MPO, PGE2, pro- and anti-inflammatory cytokines, growth factors, caspase-3, NO, K+ATP channels, and α2-receptors were investigated. Violacein exhibited significant gastroprotective effect against indomethacin-induced lesions, while pretreatment with L-NAME and glibenclamide (but not with NEM or yohimbine) was able to reverse this action. Pretreatment with violacein also restored cNOS level to normal and led to attenuation of enhanced apoptosis and gastric microvascular permeability. Our results suggest that violacein provides a significant gastroprotective effect in an indomethacin-induced ulcer model through the maintenance of some vital protein molecules, and this effect appears to be mediated, at least in part, by endogenous prostaglandins, NOS, K+ATP channel opening, and inhibition of apoptosis and gastric microvascular permeability. PMID:25162059

  2. Impaired Bone Resorption and Woven Bone Formation Are Associated with Development of Osteonecrosis of the Jaw-Like Lesions by Bisphosphonate and Anti–Receptor Activator of NF-κB Ligand Antibody in Mice

    PubMed Central

    Williams, Drake W.; Lee, Cindy; Kim, Terresa; Yagita, Hideo; Wu, Hongkun; Park, Sil; Yang, Paul; Liu, Honghu; Shi, Songtao; Shin, Ki-Hyuk; Kang, Mo K.; Park, No-Hee; Kim, Reuben H.

    2015-01-01

    Drug-induced osteonecrosis of the jaw (ONJ) is a detrimental intraoral lesion that often occurs after dental-related interventions in patients undergoing treatment with bisphosphonates or denosumab, the neutralizing human anti–receptor activator of NF-κB ligand (RANKL) antibody (Ab). The cause of ONJ by these drugs has been speculated to their direct effects on osteoclasts. However, the extent to which osteoclasts contribute to ONJ pathogenesis remains controversial. Herein, by using a tooth-extraction mouse model with i.v. administration of mouse anti-RANKL Ab or the bisphosphonate zoledronate (ZOL), we show that unresorbed bone due to impaired formation or suppressed functions of osteoclasts, respectively, is associated with ONJ development. After tooth extraction, ONJ-like lesions developed 50% in the anti-RANKL Ab-treated mice and 30% in the ZOL-treated mice. Nonviable and unresorbed bone was found more in anti-RANKL Ab-treated mice compared with mice receiving ZOL. All mice receiving anti-RANKL Ab had an undetectable tartrate-resistant acid phosphatase (TRAP) level in the serum and no TRAP-positive osteoclasts at the extracted sockets, whereas ZOL-treated mice had a decreased TRAP level without altering the numbers of TRAP-positive osteoclasts. Interestingly, the absence of newly formed woven bone in the extracted sockets was evident in ONJ-like lesions from both anti-RANKL Ab- and ZOL-treated mice. Our study suggests that the lack of osteoclasts' bone-resorptive functions by these drugs and suppression of woven bone formation after dental trauma may be associated with ONJ development. PMID:25173134

  3. Cystic Lesions of the Mediastinum.

    PubMed

    Vargas, Daniel; Suby-Long, Thomas; Restrepo, Carlos S

    2016-06-01

    Cystic lesions are commonly seen in the mediastinum, and they may arise from virtually any organ. The vast majority of these lesions are benign and result in no symptoms. When large, cysts may produce symptoms related to compression of adjacent structures. The most common mediastinal cysts are pericardial and foregut duplication cysts. Both computed tomography and magnetic resonance are routinely used to evaluate these lesions. Although computed tomography offers superior spatial resolution, magnetic resonance is useful in differentiating cysts that contain proteinaceous material from solid lesions. Occasionally, cysts arise from solid lesions, such as thymoma or teratoma. Although cysts are alike in appearance, location helps narrowing the differential diagnoses.

  4. Lesion mimic mutants

    PubMed Central

    Moeder, Wolfgang

    2008-01-01

    Over the last decade a substantial number of lesion mimic mutants (LMM) have been isolated and a growing number of the genes have been cloned. It is now becoming clear that these mutants are valuable tools to dissect various aspects of programmed cell death (PCD) and pathogen resistance pathways in plants. Together with other forward genetics approaches LMMs shed light on the PCD machinery in plant cells and revealed important roles for sphingolipids, Ca2+ and chloroplast-derived porphyrin-metabolites during cell death development. PMID:19513227

  5. Cryoanalgesia for painful peripheral nerve lesions.

    PubMed

    Wang, J K

    1985-06-01

    Twelve patients with chronically painful peripheral nerve lesions were treated with cryoanalgesia. The pain was relieved in 6 patients for 1-12 months. Although the pain eventually recurred, the patients resumed normal activities during remission. It is necessary to improve the techniques of nerve localization and to determine the proper mode of nerve freezing. PMID:2995903

  6. Antioxidant, Biomolecule Oxidation Protective Activities of Nardostachys jatamansi DC and Its Phytochemical Analysis by RP-HPLC and GC-MS

    PubMed Central

    Razack, Sakina; Hemanth Kumar, Kandikattu; Nallamuthu, Ilaiyaraja; Naika, Mahadeva; Khanum, Farhath

    2015-01-01

    The study aimed at analyzing the metabolite profile of Nardostachys jatamansi using RP-HPLC, GC-MS and also its antioxidant, biomolecule protective and cytoprotective properties. The 70% ethanolic extract of Nardostachys jatamansi (NJE) showed the presence of polyphenols and flavonoids (gallic acid, catechin, chlorogenic acid, homovanillin, epicatechin, rutin hydrate and quercetin-3-rhamnoside) analyzed by RP-HPLC, whereas hexane extract revealed an array of metabolites (fatty acids, sesquiterpenes, alkane hydrocarbons and esters) by GC-MS analysis. The antioxidant assays showed the enhanced potency of NJE with a half maximal inhibitory concentration (IC50) value of 222.22 ± 7.4 μg/mL for 2,2-diphenyl-1-picrylhydrazyl (DPPH), 13.90 ± 0.5 μg/mL for 2,2′-azino-bis(3-ethyl benzothiazoline-6-sulfonic acid) diammonium salt (ABTS), 113.81 ± 4.2 μg/mL for superoxide, 948 ± 21.1 μg/mL for metal chelating and 12.3 ± 0.43 mg FeSO4 equivalent/g of extract for ferric reducing antioxidant power assays and was more potent than hexane extract. NJE effectively inhibited 2,2′-azobis(2-methylpropionamidine) dihydrochloride (AAPH)-induced oxidation of biomolecules analyzed by pBR322 plasmid DNA damage, protein oxidation of bovine serum albumin and lipid peroxidation assays. The observed effects might be due to the high content of polyphenols, 53.06 ± 2.2 mg gallic acid equivalents/g, and flavonoids, 25.303 ± 0.9 mg catechin equivalents/g, of NJE compared to the hexane fraction. Additionally, the extract abrogated the protein, carbonyl, and ROS formation, and NJE showed cytotoxicity in SH-SY5Y neuronal cells above 75 μg/mL. Thus, the study suggests that the herb unequivocally is a potential source of antioxidants and could aid in alleviating oxidative stress-mediated disorders. PMID:26785345

  7. Multiple Large Tumefactive MS Plaques in a Young Man: A Diagnostic Enigma and Therapeutic Challenge.

    PubMed

    Kalanie, Hossein; Harandi, Ali Amini; Bakhshandehpour, Reza; Heidari, Daryoosh

    2012-01-01

    Tumefactive demyelinating lesion is defined as large solitary demyelinating lesion with imaging characteristics mimicking neoplasm. These atypical features include size more than 2 cm, mass effect, edema, and/or ring enhancement. Distinguishing tumefactive lesions from other etiologies of intracranial space occupying lesions is essential to avoid inadvertent surgical or toxic chemotherapeutic intervention. Symptoms are generally atypical for multiple sclerosis (MS) and usually related to the pressure of a focal mass lesion without a history of MS. The clinical presentation and MRI appearance of these lesions often lead to biopsy. Here, we present a young man with fulminating neurological symptoms and multiple large tumefactive lesions on either hemisphere. Since patient and parents were not agreed on brain biopsy, a course of steroid therapy was commenced which ended to considerable improvement and confirmed the diagnosis of tumefactive MS. Thirteen months later, he experienced another relapse when his treatment was continued by weekly intramuscular injection of interferon b1a (Avonex). Two further MRIs showed shrinkage of tumefactive plaques and resolution of edema in the periphery of lesions. PMID:22844629

  8. Multiple Large Tumefactive MS Plaques in a Young Man: A Diagnostic Enigma and Therapeutic Challenge

    PubMed Central

    Kalanie, Hossein; Harandi, Ali Amini; Bakhshandehpour, Reza; Heidari, Daryoosh

    2012-01-01

    Tumefactive demyelinating lesion is defined as large solitary demyelinating lesion with imaging characteristics mimicking neoplasm. These atypical features include size more than 2 cm, mass effect, edema, and/or ring enhancement. Distinguishing tumefactive lesions from other etiologies of intracranial space occupying lesions is essential to avoid inadvertent surgical or toxic chemotherapeutic intervention. Symptoms are generally atypical for multiple sclerosis (MS) and usually related to the pressure of a focal mass lesion without a history of MS. The clinical presentation and MRI appearance of these lesions often lead to biopsy. Here, we present a young man with fulminating neurological symptoms and multiple large tumefactive lesions on either hemisphere. Since patient and parents were not agreed on brain biopsy, a course of steroid therapy was commenced which ended to considerable improvement and confirmed the diagnosis of tumefactive MS. Thirteen months later, he experienced another relapse when his treatment was continued by weekly intramuscular injection of interferon b1a (Avonex). Two further MRIs showed shrinkage of tumefactive plaques and resolution of edema in the periphery of lesions. PMID:22844629

  9. Mechanistic evidence of Passiflora edulis (Passifloraceae) anxiolytic activity in relation to its metabolite fingerprint as revealed via LC-MS and chemometrics.

    PubMed

    Otify, Asmaa; George, Camilia; Elsayed, Aly; Farag, Mohamed A

    2015-12-01

    Passiflora edulis Sims F. flavicarpa along with several other plants belonging to the genus Passiflora have been reported as sedatives and for treatment or prevention of central disorders. This study evaluated the anxiolytic effect of P. edulis ethanol extract and its fractions (viz. chloroform, ethyl acetate and butanol) using the elevated plus-maze model of anxiety and assessment of γ-aminobutyric acid levels. The results revealed that butanol and chloroform extracts exhibit the strongest effect followed by ethyl acetate suggesting that a combination of different classes of metabolites is likely to mediate for P. edulis anxiolytic effect in these fractions. To further pinpoint bioactive agents in fractions, ultra-performance liquid chromatography (UPLC) coupled to high resolution qTOF-MS was used for secondary metabolite profiling. A total of 65 metabolites were characterized including O-flavonoids, C-flavonoids, cyanogenic glycosides and fatty acids. Harman type alkaloids found in P. incarnata were not detected in P. edulis ethanol extract or any of its fractions suggesting that they do not mediate for its CNS modulating effects. Multivariate data analysis (PCA) was further applied to identify metabolite markers for fractions and revealed that enrichment of C-glycoside type flavonoids in chloroform/ethyl acetate fractions versus the exclusive presence of cyanogenic glycosides in its butanol fraction. PMID:26437270

  10. Deconstruction of Activity-Dependent Covalent Modification of Heme in Human Neutrophil Myeloperoxidase by Multistage Mass Spectrometry (MS[superscript 4])

    SciTech Connect

    Geoghegan, Kieran F.; Varghese, Alison H.; Feng, Xidong; Bessire, Andrew J.; Conboy, James J.; Ruggeri, Roger B.; Ahn, Kay; Spath, Samantha N.; Filippov, Sergey V.; Conrad, Steven J.; Carpino, Philip A.; Guimarães, Cristiano R.W.; Vajdos, Felix F.

    2013-03-07

    Myeloperoxidase (MPO) is known to be inactivated and covalently modified by treatment with hydrogen peroxide and agents similar to 3-(2-ethoxypropyl)-2-thioxo-2,3-dihydro-1H-purin-6(9H)-one (1), a 254.08 Da derivative of 2-thioxanthine. Peptide mapping by liquid chromatography and mass spectrometry detected modification by 1 in a labile peptide-heme-peptide fragment of the enzyme, accompanied by a mass increase of 252.08 Da. The loss of two hydrogen atoms was consistent with mechanism-based oxidative coupling. Multistage mass spectrometry (MS{sup 4}) of the modified fragment in an ion trap/Orbitrap spectrometer demonstrated that 1 was coupled directly to heme. Use of a 10 amu window delivered the full isotopic envelope of each precursor ion to collision-induced dissociation, preserving definitive isotopic profiles for iron-containing fragments through successive steps of multistage mass spectrometry. Iron isotope signatures and accurate mass measurements supported the structural assignments. Crystallographic analysis confirmed linkage between the methyl substituent of the heme pyrrole D ring and the sulfur atom of 1. The final orientation of 1 perpendicular to the plane of the heme ring suggested a mechanism consisting of two consecutive one-electron oxidations of 1 by MPO. Multistage mass spectrometry using stage-specific collision energies permits stepwise deconstruction of modifications of heme enzymes containing covalent links between the heme group and the polypeptide chain.

  11. Cognitive impairment in MS: rehabilitation approaches.

    PubMed

    Hämäläinen, P; Rosti-Otajärvi, E

    2016-09-01

    Cognitive deficits have been reported in 45%-70% of patients with multiple sclerosis (MS). Like other symptoms of MS, cognitive deficits are highly variable. Slowed information processing and memory and learning dysfunction are regarded as the most frequent cognitive deficits in MS. Both white and gray matter damages have been suggested to contribute to cognitive impairments in MS. There is no direct relationship between cognitive deficits and physical disability, disease duration or course of the disease. In addition to cognitive impairments, neuropsychiatric symptoms are observed in MS, the most common being alterations in mood state. Neurobehavioral deficits have multidimensional effects on the activities of daily living and quality of life. Consequently, attention should be paid to early diagnosis and treatment. Based on studies on cognitive retraining and more multimodal neuropsychological rehabilitation, both approaches show promise in the treatment of cognitive impairments and their harmful effects. This review introduces the frequency and characteristics of cognitive impairments, as well as main findings on the effects of neuropsychological rehabilitation in MS. PMID:27580900

  12. Sodium MRI in Multiple Sclerosis is Compatible with Intracellular Sodium Accumulation and Inflammation-Induced Hyper-Cellularity of Acute Brain Lesions

    PubMed Central

    Biller, Armin; Pflugmann, Isabella; Badde, Stephanie; Diem, Ricarda; Wildemann, Brigitte; Nagel, Armin M.; Jordan, J.; Benkhedah, Nadia; Kleesiek, Jens

    2016-01-01

    The cascade of inflammatory pathogenetic mechanisms in multiple sclerosis (MS) has no specific conventional MRI correlates. Clinicians therefore stipulate improved imaging specificity to define the pathological substrates of MS in vivo including mapping of intracellular sodium accumulation. Based upon preclinical findings and results of previous sodium MRI studies in MS patients we hypothesized that the fluid-attenuated sodium signal differs between acute and chronic lesions. We acquired brain sodium and proton MRI data of N = 29 MS patients; lesion type was defined by the presence or absence of contrast enhancement. N = 302 MS brain lesions were detected, and generalized linear mixed models were applied to predict lesion type based on sodium signals; thereby controlling for varying numbers of lesions among patients and confounding variables such as age and medication. Hierarchical model comparisons revealed that both sodium signals average tissue (χ2(1) = 27.89, p < 0.001) and fluid-attenuated (χ2(1) = 5.76, p = 0.016) improved lesion type classification. Sodium MRI signals were significantly elevated in acute compared to chronic lesions compatible with intracellular sodium accumulation in acute MS lesions. If confirmed in further studies, sodium MRI could serve as biomarker for diagnostic assessment of MS, and as readout parameter in clinical trials promoting attenuation of chronic inflammation. PMID:27507776

  13. Sodium MRI in Multiple Sclerosis is Compatible with Intracellular Sodium Accumulation and Inflammation-Induced Hyper-Cellularity of Acute Brain Lesions.

    PubMed

    Biller, Armin; Pflugmann, Isabella; Badde, Stephanie; Diem, Ricarda; Wildemann, Brigitte; Nagel, Armin M; Jordan, J; Benkhedah, Nadia; Kleesiek, Jens

    2016-01-01

    The cascade of inflammatory pathogenetic mechanisms in multiple sclerosis (MS) has no specific conventional MRI correlates. Clinicians therefore stipulate improved imaging specificity to define the pathological substrates of MS in vivo including mapping of intracellular sodium accumulation. Based upon preclinical findings and results of previous sodium MRI studies in MS patients we hypothesized that the fluid-attenuated sodium signal differs between acute and chronic lesions. We acquired brain sodium and proton MRI data of N = 29 MS patients; lesion type was defined by the presence or absence of contrast enhancement. N = 302 MS brain lesions were detected, and generalized linear mixed models were applied to predict lesion type based on sodium signals; thereby controlling for varying numbers of lesions among patients and confounding variables such as age and medication. Hierarchical model comparisons revealed that both sodium signals average tissue (χ(2)(1) = 27.89, p < 0.001) and fluid-attenuated (χ(2)(1) = 5.76, p = 0.016) improved lesion type classification. Sodium MRI signals were significantly elevated in acute compared to chronic lesions compatible with intracellular sodium accumulation in acute MS lesions. If confirmed in further studies, sodium MRI could serve as biomarker for diagnostic assessment of MS, and as readout parameter in clinical trials promoting attenuation of chronic inflammation. PMID:27507776

  14. [Caring for perilesional skin or skin having a lesion risk].

    PubMed

    Segovia, Gómez T; Javares, Curto T; Barahona, M; Verdú, Soriano J

    2007-10-01

    In order to increase the clinical and scientific evidence of the Hyperoxygenated Fatty Acids (HFA) in emulsion preparation for skin care, this study considers to evaluate prospectively how it influences in the state of the periwound skin (when there are active lesions) or in which it presents a high risk of lesion production.

  15. Treatment optimization in MS: Canadian MS Working Group updated recommendations.

    PubMed

    Freedman, Mark S; Selchen, Daniel; Arnold, Douglas L; Prat, Alexandre; Banwell, Brenda; Yeung, Michael; Morgenthau, David; Lapierre, Yves

    2013-05-01

    The Canadian Multiple Sclerosis Working Group (CMSWG) developed practical recommendations in 2004 to assist clinicians in optimizing the use of disease-modifying therapies (DMT) in patients with relapsing multiple sclerosis. The CMSWG convened to review how disease activity is assessed, propose a more current approach for assessing suboptimal response, and to suggest a scheme for switching or escalating treatment. Practical criteria for relapses, Expanded Disability Status Scale (EDSS) progression and MRI were developed to classify the clinical level of concern as Low, Medium and High. The group concluded that a change in treatment may be considered in any RRMS patient if there is a high level of concern in any one domain (relapses, progression or MRI), a medium level of concern in any two domains, or a low level of concern in all three domains. These recommendations for assessing treatment response should assist clinicians in making more rational choices in their management of relapsing MS patients. PMID:23603165

  16. LC-MS/MS quantitation of plasma progesterone in cattle.

    PubMed

    Fernandes, R M T; Gomes, G C; Porcari, A M; Pimentel, J R V; Porciúncula, P M; Martins-Júnior, H A; Miguez, P H P; da Costa, J L; Amaral, P H; Perecin, F; Meurer, E C; Furtado, P V; Simas, R C; Eberlin, M N; Ferreira, C R; Madureira, E H

    2011-10-15

    Quantitation of progesterone (P(4)) in biological fluids is often performed by radioimmunoassay (RIA), whereas liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) has been used much less often. Due to its autoconfirmatory nature, LC-MS/MS greatly minimizes false positives and interference. Herein we report and compare with RIA an optimized LC-MS/MS method for rapid, efficient, and cost-effective quantitation of P(4) in plasma of cattle with no sample derivatization. The quantitation of plasma P(4) released from three nonbiodegradable, commercial, intravaginal P(4)-releasing devices (IPRD) over 192 h in six ovariectomized cows was compared in a pairwise study as a test case. Both techniques showed similar P(4) kinetics (P > 0.05) whereas results of P(4) quantitation by RIA were consistently higher compared with LC-MS/MS (P < 0.05) due to interference and matrix effects. The LC-MS/MS method was validated according to the recommended analytical standards and displayed P(4) limits of detection (LOD) and quantitation (LOQ) of 0.08 and a 0.25 ng/mL, respectively. The high selective LC-MS/MS method proposed herein for P(4) quantitation eliminates the risks associated with radioactive handling; it also requires no sample derivatization, which is a common requirement for LC-MS/MS quantitation of steroid hormones. Its application to multisteroid assays is also viable, and it is envisaged that it may provide a gold standard technique for hormone quantitation in animal reproductive science studies. PMID:21798587

  17. GC-MS-olfactometric characterization of the most aroma-active components in a representative aromatic extract from Iranian saffron (Crocus sativus L.).

    PubMed

    Amanpour, Asghar; Sonmezdag, A Salih; Kelebek, Hasim; Selli, Serkan

    2015-09-01

    Aroma and aroma-active compounds of Iranian saffron (Crocus sativus L.) were analyzed by gas chromatography-mass spectrometry-olfactometry. The saffron aromatic extracts were obtained by four different extraction techniques including solvent-assisted flavour evaporation (SAFE), liquid-liquid extraction (LLE), solid phase extraction (SPE), and simultaneous distillation extraction (SDE) and compared to achieve a representative aromatic extract from saffron. According to sensory analysis, the aromatic extract obtained by SAFE was the most representative of saffron odour. A total of 28 aroma compounds were identified in saffron. Ketones were quantitatively the most dominant volatiles in saffron, followed by aldehydes and acids. Aroma extract dilution analysis (AEDA) was used for the determination of aroma-active compounds of saffron. A total of nine aroma-active compounds were detected in the aromatic extract. On the basis of the flavour dilution (FD) factor, the most powerful aroma active compounds were safranal (FD = 512), 4-ketoisophorone (FD = 256) and dihydrooxophorone (FD = 128).

  18. A Model of Population and Subject (MOPS) Intensities with Application to Multiple Sclerosis Lesion Segmentation

    PubMed Central

    Tomas-Fernandez, Xavier; Warfield, Simon K.

    2015-01-01

    White matter (WM) lesions are thought to play an important role in multiple sclerosis (MS) disease burden. Recent work in the automated segmentation of white matter lesions from MRI has utilized a model in which lesions are outliers in the distribution of tissue signal intensities across the entire brain of each patient. However, the sensitivity and specificity of lesion detection and segmentation with these approaches have been inadequate. In our analysis, we determined this is due to the substantial overlap between the whole brain signal intensity distribution of lesions and normal tissue. Inspired by the ability of experts to detect lesions based on their local signal intensity characteristics, we propose a new algorithm that achieves lesion and brain tissue segmentation through simultaneous estimation of a spatially global within-the-subject intensity distribution and a spatially local intensity distribution derived from a healthy reference population. We demonstrate that MS lesions can be segmented as outliers from this intensity model of population and subject (MOPS). We carried out extensive experiments with both synthetic and clinical data, and compared the performance of our new algorithm to those of state-of-the art techniques. We found this new approach leads to a substantial improvement in the sensitivity and specificity of lesion detection and segmentation. PMID:25616008

  19. Thalamic Lesions: A Radiological Review

    PubMed Central

    Renard, Dimitri; Campello, Chantal; Bouly, Stephane; Le Floch, Anne; Thouvenot, Eric; Waconge, Anne; Taieb, Guillaume

    2014-01-01

    Background. Thalamic lesions are seen in a multitude of disorders including vascular diseases, metabolic disorders, inflammatory diseases, trauma, tumours, and infections. In some diseases, thalamic involvement is typical and sometimes isolated, while in other diseases thalamic lesions are observed only occasionally (often in the presence of other typical extrathalamic lesions). Summary. In this review, we will mainly discuss the MRI characteristics of thalamic lesions. Identification of the origin of the thalamic lesion depends on the exact localisation inside the thalamus, the presence of extrathalamic lesions, the signal changes on different MRI sequences, the evolution of the radiological abnormalities over time, the history and clinical state of the patient, and other radiological and nonradiological examinations. PMID:25100900

  20. Spine and sacroiliac joints on magnetic resonance imaging in patients with early axial spondyloarthritis: prevalence of lesions and association with clinical and disease activity indices from the Italian group of the SPACE study.

    PubMed

    Lorenzin, M; Ortolan, A; Frallonardo, P; Vio, S; Lacognata, C; Oliviero, F; Punzi, L; Ramonda, R

    2016-01-01

    Our aim was to determine the prevalence of spine and sacroiliac joint (SIJ) lesions on magnetic resonance imaging (MRI) in patients with early axial spondyloarthritis (axSpA) and their correlation with disease activity indices. Sixty patients with low back pain (LBP) (≥3 months, ≤2 years, onset ≤45 years), attending the SpA-clinic of the Unità Operativa Complessa Reumatologia of Padova [SpondyloArthritis-Caught-Early (SPACE) study], were studied following a protocol including physical examination, questionnaires, laboratory tests, X-rays and spine and SIJ MRI. Positive spine and SIJ MRI and X-rays images were scored independently by 2 readers using the SPARCC method, modified Stoke ankylosing spondylitis spine score and New York criteria. The axial pain and localization of MRI-lesions were referred to 4 sites: cervical/thoracic/lumbar spine and SIJ. All patients were classified into three groups: patients with signs of radiographic sacroiliitis (r-axSpA), patients without signs of r-axSpA but with signs of sacroiliitis on MRI (nr-axSpA MRI SIJ+), patients without signs of sacroiliitis on MRI and X-rays (nr-axSpA MRI SIJ-). The median age at LBP onset was 29.05±8.38 years; 51.6% of patients showed bone marrow edema (BME) in spine-MRI and 56.7% of patients in SIJ-MRI. Signs of enthesitis were found in 55% of patients in the thoracic district. Of the 55% of patients with BME on spine-MRI, 15% presented presented a negative SIJMRI. There was a significant difference between these cohorts with regard to the prevalence of radiographic sacroiliitis, active sacroiliitis on MRI and SPARCC SIJ score. The site of pain correlated statistically with BME lesions in thoracic and buttock districts. Since positive spine-MRI images were observed in absence of sacroiliitis, we can hypothesize that this finding could have a diagnostic significance in axSpA suspected axSpA. PMID:27608795

  1. Multiple sclerosis lesion quantification in MR images by using vectorial scale-based relative fuzzy connectedness

    NASA Astrophysics Data System (ADS)

    Zhuge, Ying; Udupa, Jayaram K.; Nyul, Laszlo G.

    2004-05-01

    This paper presents a methodology for segmenting PD- and T2-weighted brain magnetic resonance (MR) images of multiple sclerosis (MS) patients into white matter (WM), gray matter (GM), cerebrospinal fluid (CSF), and MS lesions. For a given vectorial image (with PD- and T2-weighted components) to be segmented, we perform first intensity inhomogeneity correction and standardization prior to segmentation. Absolute fuzzy connectedness and certain morphological operations are utilized to generate the brain intracranial mask. The optimum thresholding method is applied to the product image (the image in which voxel values represent T2 value x PD value) to automatically recognize potential MS lesion sites. Then, the recently developed technique -- vectorial scale-based relative fuzzy connectedness -- is utilized to segment all voxels within the brain intracranial mask into WM, GM, CSF, and MS lesion regions. The number of segmented lesions and the volume of each lesion are finally output as well as the volume of other tissue regions. The method has been tested on 10 clinical brain MRI data sets of MS patients. An accuracy of better than 96% has been achieved. The preliminary results indicate that its performance is better than that of the k-nearest neighbors (kNN) method.

  2. Quantifying brain tissue volume in multiple sclerosis with automated lesion segmentation and filling.

    PubMed

    Valverde, Sergi; Oliver, Arnau; Roura, Eloy; Pareto, Deborah; Vilanova, Joan C; Ramió-Torrentà, Lluís; Sastre-Garriga, Jaume; Montalban, Xavier; Rovira, Àlex; Lladó, Xavier

    2015-01-01

    Lesion filling has been successfully applied to reduce the effect of hypo-intense T1-w Multiple Sclerosis (MS) lesions on automatic brain tissue segmentation. However, a study of fully automated pipelines incorporating lesion segmentation and lesion filling on tissue volume analysis has not yet been performed. Here, we analyzed the % of error introduced by automating the lesion segmentation and filling processes in the tissue segmentation of 70 clinically isolated syndrome patient images. First of all, images were processed using the LST and SLS toolkits with different pipeline combinations that differed in either automated or manual lesion segmentation, and lesion filling or masking out lesions. Then, images processed following each of the pipelines were segmented into gray matter (GM) and white matter (WM) using SPM8, and compared with the same images where expert lesion annotations were filled before segmentation. Our results showed that fully automated lesion segmentation and filling pipelines reduced significantly the % of error in GM and WM volume on images of MS patients, and performed similarly to the images where expert lesion annotations were masked before segmentation. In all the pipelines, the amount of misclassified lesion voxels was the main cause in the observed error in GM and WM volume. However, the % of error was significantly lower when automatically estimated lesions were filled and not masked before segmentation. These results are relevant and suggest that LST and SLS toolboxes allow the performance of accurate brain tissue volume measurements without any kind of manual intervention, which can be convenient not only in terms of time and economic costs, but also to avoid the inherent intra/inter variability between manual annotations.

  3. Quantifying brain tissue volume in multiple sclerosis with automated lesion segmentation and filling

    PubMed Central

    Valverde, Sergi; Oliver, Arnau; Roura, Eloy; Pareto, Deborah; Vilanova, Joan C.; Ramió-Torrentà, Lluís; Sastre-Garriga, Jaume; Montalban, Xavier; Rovira, Àlex; Lladó, Xavier

    2015-01-01

    Lesion filling has been successfully applied to reduce the effect of hypo-intense T1-w Multiple Sclerosis (MS) lesions on automatic brain tissue segmentation. However, a study of fully automated pipelines incorporating lesion segmentation and lesion filling on tissue volume analysis has not yet been performed. Here, we analyzed the % of error introduced by automating the lesion segmentation and filling processes in the tissue segmentation of 70 clinically isolated syndrome patient images. First of all, images were processed using the LST and SLS toolkits with different pipeline combinations that differed in either automated or manual lesion segmentation, and lesion filling or masking out lesions. Then, images processed following each of the pipelines were segmented into gray matter (GM) and white matter (WM) using SPM8, and compared with the same images where expert lesion annotations were filled before segmentation. Our results showed that fully automated lesion segmentation and filling pipelines reduced significantly the % of error in GM and WM volume on images of MS patients, and performed similarly to the images where expert lesion annotations were masked before segmentation. In all the pipelines, the amount of misclassified lesion voxels was the main cause in the observed error in GM and WM volume. However, the % of error was significantly lower when automatically estimated lesions were filled and not masked before segmentation. These results are relevant and suggest that LST and SLS toolboxes allow the performance of accurate brain tissue volume measurements without any kind of manual intervention, which can be convenient not only in terms of time and economic costs, but also to avoid the inherent intra/inter variability between manual annotations. PMID:26740917

  4. Divergent Trends of Anti-JCPyV Serum Reactivity and Neutralizing Activity in Multiple Sclerosis (MS) Patients during Treatment with Natalizumab

    PubMed Central

    Diotti, Roberta Antonia; Capra, Ruggero; Moiola, Lucia; Caputo, Valeria; De Rossi, Nicola; Sangalli, Francesca; Martinelli, Vittorio; Burioni, Roberto; Clementi, Massimo; Mancini, Nicasio

    2016-01-01

    The association between natalizumab and progressive multifocal leukoencephalopathy (PML) is established, but a reliable clinical risk stratification flow-chart is lacking. New risk factors are needed, such as the possible role of the anti-JC polyomavirus (JCPyV) neutralizing antibody. In this pilot study, we analyzed this parameter during natalizumab treatment. Sequential sera of 38 multiple sclerosis patients during their first year of natalizumab treatment were collected, and grouped according to the number of infusions. For 11 patients, samples were also available after 24 infusions (T24), when progressive multifocal leukoencephalopathy (PML) risk is higher. The reactivity against VP1, the main JCPyV surface protein, and the anti-JCPyV neutralizing activity were evaluated. During the first year, a lack of correlation between anti-JCPyV antibody response and its neutralizing activity was observed: a significant decrease in anti-JCPyV antibody response was observed (p = 0.0039), not paralleled by a similar trend in the total anti-JCPyV neutralizing activity (p = 0.2239). This lack of correlation was even more evident at T24 when, notwithstanding a significant increase in the anti-JCPyV response (p = 0.0097), a further decrease of the neutralizing activity was observed (p = 0.0062). This is the first study evidencing, prospectively, the lack of correlation between the anti-JCPyV antibody response and its neutralizing activity during natalizumab treatment. PMID:27164128

  5. Divergent Trends of Anti-JCPyV Serum Reactivity and Neutralizing Activity in Multiple Sclerosis (MS) Patients during Treatment with Natalizumab.

    PubMed

    Diotti, Roberta Antonia; Capra, Ruggero; Moiola, Lucia; Caputo, Valeria; De Rossi, Nicola; Sangalli, Francesca; Martinelli, Vittorio; Burioni, Roberto; Clementi, Massimo; Mancini, Nicasio

    2016-01-01

    The association between natalizumab and progressive multifocal leukoencephalopathy (PML) is established, but a reliable clinical risk stratification flow-chart is lacking. New risk factors are needed, such as the possible role of the anti-JC polyomavirus (JCPyV) neutralizing antibody. In this pilot study, we analyzed this parameter during natalizumab treatment. Sequential sera of 38 multiple sclerosis patients during their first year of natalizumab treatment were collected, and grouped according to the number of infusions. For 11 patients, samples were also available after 24 infusions (T24), when progressive multifocal leukoencephalopathy (PML) risk is higher. The reactivity against VP1, the main JCPyV surface protein, and the anti-JCPyV neutralizing activity were evaluated. During the first year, a lack of correlation between anti-JCPyV antibody response and its neutralizing activity was observed: a significant decrease in anti-JCPyV antibody response was observed (p = 0.0039), not paralleled by a similar trend in the total anti-JCPyV neutralizing activity (p = 0.2239). This lack of correlation was even more evident at T24 when, notwithstanding a significant increase in the anti-JCPyV response (p = 0.0097), a further decrease of the neutralizing activity was observed (p = 0.0062). This is the first study evidencing, prospectively, the lack of correlation between the anti-JCPyV antibody response and its neutralizing activity during natalizumab treatment. PMID:27164128

  6. Development of an LC-MS method for ultra trace-level determination of 2,2,6,6-tetramethylpiperidine-1-oxl (TEMPO), a potential genotoxic impurity within active pharmaceutical ingredients.

    PubMed

    Pennington, Justin; Cohen, Ryan D; Tian, Ye; Boulineau, Fabien

    2015-10-10

    TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl) is a stable free radical which has been widely used for various research and industrial applications, including the manufacture of many active pharmaceutical ingredients. TEMPO has been identified as a potential genotoxic impurity resulting in the need for analytical methodology to accurately determine its level at several orders of magnitude less than typical impurity quantitation limits. TEMPO can undergo disproportionation to form both oxidized and reduced TEMPO, making individual determination unreliable. To overcome this challenge, all TEMPO related species were converted to the reduced form through reduction with sodium ascorbate. Given the ultra-trace (0.5 ppm) level requirements and the lack of UV response in the reduced form, a single quadrupole mass spectrometer (MS) was utilized. In order to implement a highly sensitive MS method in a GMP environment, several approaches were employed to optimize accuracy and robustness including: internal standard correction for drift elimination, six-level standard addition to reduce matrix effects, and weighted linear regression to cover a broad analytical range. The method was fully validated according to ICH guidelines. The method is specific, linear, accurate, precise, and robust within a range of 0.5-100 ppm.

  7. Pigmented Lesion of Buccal Mucosa

    PubMed Central

    Bajpai, Manas; Kumar, Malay; Kumar, Manish; Agarwal, Deshant

    2014-01-01

    Pigmented lesions are commonly found in the mouth. Such lesions represent a variety of clinical entities, ranging from physiologic changes to manifestation of systemic illness and malignant neoplasm. Diagnosis of such lesions requires a proper case history, extraoral and intraoral examination, and, in some cases, biopsy, aspiration cytology, and laboratory investigations. Here we present a case of purple lesion on the buccal mucosa of a 34-year-old male patient which was provisionally diagnosed as mucocele but on the basis of histopathological picture it was finally diagnosed as angiofibroma, and we also discuss the clinical and histopathological differential diagnosis. PMID:25161669

  8. Stress-induced cervical lesions.

    PubMed

    Braem, M; Lambrechts, P; Vanherle, G

    1992-05-01

    The increasing occurrence of dental lesions at the cervical surfaces requires more knowledge of the causes of the process. Acidic and abrasive mechanisms have clearly been documented as causes but the stress theory by Lee and Eakle is still controversial. This report describes several incidences of possible stress-induced lesions according to the characteristics described by Lee and Eakle. The occurrences of subgingival lesions lend credence to the stress-induction theory by exclusion of other superimposing etiologic factors. With the current concepts, a perceptive approach to the treatment of cervical lesions can be executed. PMID:1527763

  9. Polyamine analysis by LC-MS.

    PubMed

    Häkkinen, Merja R

    2011-01-01

    This chapter describes a protocol to analyze polyamines without any derivatization steps utilizing LC-MS/MS. Polyamines are separated by reversed phase LC prior MS analysis using heptafluorobutyric acid as MS compatible volatile ion-pairing agent, and selective and sensitive MS detection is performed using MS/MS in selected reaction monitoring mode.

  10. Segmentation of multiple sclerosis lesions using support vector machines

    NASA Astrophysics Data System (ADS)

    Ferrari, Ricardo J.; Wei, Xingchang; Zhang, Yunyan; Scott, James N.; Mitchell, J. R.

    2003-05-01

    In this paper we present preliminary results to automatically segment multiple sclerosis (MS) lesions in multispectral magnetic resonance datasets using support vector machines (SVM). A total of eighteen studies (each composed of T1-, T2-weighted and FLAIR images) acquired from a 3T GE Signa scanner was analyzed. A neuroradiologist used a computer-assisted technique to identify all MS lesions in each study. These results were used later in the training and testing stages of the SVM classifier. A preprocessing stage including anisotropic diffusion filtering, non-uniformity intensity correction, and intensity tissue normalization was applied to the images. The SVM kernel used in this study was the radial basis function (RBF). The kernel parameter (γ) and the penalty value for the errors were determined by using a very loose stopping criterion for the SVM decomposition. Overall, a 5-fold cross-validation accuracy rate of 80% was achieved in the automatic classification of MS lesion voxels using the proposed SVM-RBF classifier.

  11. Performance evaluation for volumetric segmentation of multiple sclerosis lesions using MATLAB and computing engine in the graphical processing unit (GPU)

    NASA Astrophysics Data System (ADS)

    Le, Anh H.; Park, Young W.; Ma, Kevin; Jacobs, Colin; Liu, Brent J.

    2010-03-01

    Multiple Sclerosis (MS) is a progressive neurological disease affecting myelin pathways in the brain. Multiple lesions in the white matter can cause paralysis and severe motor disabilities of the affected patient. To solve the issue of inconsistency and user-dependency in manual lesion measurement of MRI, we have proposed a 3-D automated lesion quantification algorithm to enable objective and efficient lesion volume tracking. The computer-aided detection (CAD) of MS, written in MATLAB, utilizes K-Nearest Neighbors (KNN) method to compute the probability of lesions on a per-voxel basis. Despite the highly optimized algorithm of imaging processing that is used in CAD development, MS CAD integration and evaluation in clinical workflow is technically challenging due to the requirement of high computation rates and memory bandwidth in the recursive nature of the algorithm. In this paper, we present the development and evaluation of using a computing engine in the graphical processing unit (GPU) with MATLAB for segmentation of MS lesions. The paper investigates the utilization of a high-end GPU for parallel computing of KNN in the MATLAB environment to improve algorithm performance. The integration is accomplished using NVIDIA's CUDA developmental toolkit for MATLAB. The results of this study will validate the practicality and effectiveness of the prototype MS CAD in a clinical setting. The GPU method may allow MS CAD to rapidly integrate in an electronic patient record or any disease-centric health care system.

  12. MS-DIAL: Data Independent MS/MS Deconvolution for Comprehensive Metabolome Analysis

    PubMed Central

    Tsugawa, Hiroshi; Cajka, Tomas; Kind, Tobias; Ma, Yan; Higgins, Brendan; Ikeda, Kazutaka; Kanazawa, Mitsuhiro; VanderGheynst, Jean; Fiehn, Oliver; Arita, Masanori

    2015-01-01

    Data-independent acquisition (DIA) in liquid chromatography tandem mass spectrometry (LC-MS/MS) provides more comprehensive untargeted acquisition of molecular data. Here we provide an open-source software pipeline, MS-DIAL, to demonstrate how DIA improves simultaneous identification and quantification of small molecules by mass spectral deconvolution. For reversed phase LC-MS/MS, our program with an enriched LipidBlast library identified total 1,023 lipid compounds from nine algal strains to highlight their chemotaxonomic relationships. PMID:25938372

  13. Lesions in Guddesn's tegmental nuclei produce behavioral and 5-HT effects similar to those after raphe lesions.

    PubMed

    Lorens, S A; Köhler, C; Guldberg, H C

    1975-01-01

    Lesions largely restricted to the dorsal and ventral tegmental nuclei of Gudden (GTN) produced several effects similar to those seen after midbrain raphe lesions. GTN lesions significantly reduced the 5-hydroxytryptamine (5-HT) concentration of the diencephalon (31 percent), hippocampus (59 percent), and remaining portion of the telencephalon (29 percent). Striatal 5-HT, however, was not affected. GTN lesions enhanced activity in an enclosed field and facilitated two-way avoidance acquisition. Pain sensitivity as measured by the flinch-jump method was not affected. These results suggest that the GTN may be the origin of ascending 5-HT fides and may be involved in the regulation of activity level and the adaptation of an animal to aversive situations. Thus, some of the behavioral and 5-HT effects of lesions in the midbrain raphe nuclei may be due to their involvement of the GTN and associated pathways. PMID:1187729

  14. Copper Accumulation and Lipid Oxidation Precede Inflammation and Myelin Lesions in N,N-Diethyldithiocarbamate Peripheral Myelinopathy

    PubMed Central

    Viquez, Olga M.; Valentine, Holly L.; Amarnath, Kalyani; Milatovic, Dejan; Valentine, William M.

    2008-01-01

    Dithiocarbamates have a wide spectrum of applications in industry, agriculture and medicine with new applications being actively investigated. One adverse effect of dithiocarbamates is the neurotoxicity observed in humans and experimental animals. Results from previous studies have suggested that dithiocarbamates elevate copper and promote lipid oxidation within myelin membranes. In the current study, copper levels, lipid oxidation, protein oxidative damage and markers of inflammation were monitored as a function of N,N-diethyldithiocarbmate (DEDC) exposure duration in an established model for DEDC-mediated myelinopathy in the rat. Intraabdominal administration of DEDC was performed using osmotic pumps for periods of 2, 4, and 8 weeks. Metals in brain, liver and tibial nerve were measured using ICP-MS and lipid oxidation assessed through HPLC measurement of malondialdehyde in tibial nerve, and GC/MS measurement of F2 isoprostanes in sciatic nerve. Protein oxidative injury of sciatic nerve proteins was evaluated through quantification of 4-hydroxynonenal protein adducts using immunoassay, and inflammation monitored by quantifying levels of IgGs and activated macrophages using immunoassay and immunhistochemistry methods, respectively. Changes in these parameters were then correlated to the onset of structural lesions, determined by light and electron microscopy, to delineate the temporal relationship of copper accumulation and oxidative stress in peripheral nerve to the onset of myelin lesions. The data provide evidence that DEDC mediates lipid oxidation and elevation of total copper in peripheral nerve well before myelin lesions or activated macrophages are evident. This relationship is consistent with copper-mediated oxidative stress contributing to the myelinopathy. PMID:18284930

  15. Copper accumulation and lipid oxidation precede inflammation and myelin lesions in N,N-diethyldithiocarbamate peripheral myelinopathy

    SciTech Connect

    Viquez, Olga M.; Valentine, Holly L.; Amarnath, Kalyani; Milatovic, Dejan; Valentine, William M.

    2008-05-15

    Dithiocarbamates have a wide spectrum of applications in industry, agriculture and medicine with new applications being actively investigated. One adverse effect of dithiocarbamates is the neurotoxicity observed in humans and experimental animals. Results from previous studies have suggested that dithiocarbamates elevate copper and promote lipid oxidation within myelin membranes. In the current study, copper levels, lipid oxidation, protein oxidative damage and markers of inflammation were monitored as a function of N,N-diethyldithiocarbamate (DEDC) exposure duration in an established model for DEDC-mediated myelinopathy in the rat. Intra-abdominal administration of DEDC was performed using osmotic pumps for periods of 2, 4, and 8 weeks. Metals in brain, liver and tibial nerve were measured using ICP-MS and lipid oxidation assessed through HPLC measurement of malondialdehyde in tibial nerve, and GC/MS measurement of F{sub 2} isoprostanes in sciatic nerve. Protein oxidative injury of sciatic nerve proteins was evaluated through quantification of 4-hydroxynonenal protein adducts using immunoassay, and inflammation monitored by quantifying levels of IgGs and activated macrophages using immunoassay and immunohistochemistry methods, respectively. Changes in these parameters were then correlated to the onset of structural lesions, determined by light and electron microscopy, to delineate the temporal relationship of copper accumulation and oxidative stress in peripheral nerve to the onset of myelin lesions. The data provide evidence that DEDC mediates lipid oxidation and elevation of total copper in peripheral nerve well before myelin lesions or activated macrophages are evident. This relationship is consistent with copper-mediated oxidative stress contributing to the myelinopathy.

  16. Determination of methyl and ethyl esters of methanesulfonic, benzenesulfonic and p-toluenesulfonic acids in active pharmaceutical ingredients by solid-phase microextraction (SPME) coupled to GC/SIM-MS.

    PubMed

    Colón, Ivelisse; Richoll, Stephen M

    2005-09-15

    The development, optimization and validation of an extraction method for methyl and ethyl esters of various sulfonic acids is presented. The extraction and determination of these esters in active pharmaceutical ingredients (APIs) was accomplished using solid-phase microextraction coupled to GC/MS in the SIM mode. The factors affecting the extraction efficiency are discussed. This method was validated as a limits test and allows the determination of the sulfonic esters at the 5 ppm level in APIs. The method proved to be reproducible (%R.S.D.s less than 6%) and suitable for use with external standard quantitation, and also met basic validation requirements. This method offers numerous advantages over liquid-liquid extraction methods and was also compared to other extraction techniques such as solid-phase extraction (SPE) and liquid-phase microextraction (LPME) also being developed in our laboratories.

  17. [The focal renal lesions].

    PubMed

    Tuma, Jan

    2013-06-01

    The focal renal lesions are altogether common. Most frequently are found Columna Bertini hypertrophies (so called pseudotumors) and simple renal cysts. The role of sonography in the practice is to distinguish pseudotumors from real renal tumors, and simple renal cysts from complex cysts. The differentiation of complex renal cysts is possible with the help of the CEUS (= contrast enhanced ultrasound) and other imaging modalities such as CT or MRI. In these cases, the CEUS imaging agent has clear advantages over CT and MRI, because it is composed of gas bubbles, which are only slightly smaller than red blood cells and remains exclusively intravascularly while the CT and MRI contrast agents diffuse into the interstitial space without any real perfusion. The real tumors can be differentiated from certain focal non-tumorous changes based on the ultrasound and clinic. The further differentiation of individual kidney tumors and metastases using ultrasound, MRI, CT and CEUS is only partly possible. In all uncertain or unclear cases, therefore, an open or ultrasound-guided biopsy is useful.

  18. Quantitative lipopolysaccharide analysis using HPLC/MS/MS and its combination with the limulus amebocyte lysate assay.

    PubMed

    Pais de Barros, Jean-Paul; Gautier, Thomas; Sali, Wahib; Adrie, Christophe; Choubley, Hélène; Charron, Emilie; Lalande, Caroline; Le Guern, Naig; Deckert, Valérie; Monchi, Mehran; Quenot, Jean-Pierre; Lagrost, Laurent

    2015-07-01

    Quantitation of plasma lipopolysaccharides (LPSs) might be used to document Gram-negative bacterial infection. In the present work, LPS-derived 3-hydroxymyristate was extracted from plasma samples with an organic solvent, separated by reversed phase HPLC, and quantitated by MS/MS. This mass assay was combined with the limulus amebocyte lysate (LAL) bioassay to monitor neutralization of LPS activity in biological samples. The described HPLC/MS/MS method is a reliable, practical, accurate, and sensitive tool to quantitate LPS. The combination of the LAL and HPLC/MS/MS analyses provided new evidence for the intrinsic capacity of plasma lipoproteins and phospholipid transfer protein to neutralize the activity of LPS. In a subset of patients with systemic inflammatory response syndrome, with documented infection but with a negative plasma LAL test, significant amounts of LPS were measured by the HPLC/MS/MS method. Patients with the highest plasma LPS concentration were more severely ill. HPLC/MS/MS is a relevant method to quantitate endotoxin in a sample, to assess the efficacy of LPS neutralization, and to evaluate the proinflammatory potential of LPS in vivo. PMID:26023073

  19. Quantitative lipopolysaccharide analysis using HPLC/MS/MS and its combination with the limulus amebocyte lysate assay[S

    PubMed Central

    Pais de Barros, Jean-Paul; Gautier, Thomas; Sali, Wahib; Adrie, Christophe; Choubley, Hélène; Charron, Emilie; Lalande, Caroline; Le Guern, Naig; Deckert, Valérie; Monchi, Mehran; Quenot, Jean-Pierre; Lagrost, Laurent

    2015-01-01

    Quantitation of plasma lipopolysaccharides (LPSs) might be used to document Gram-negative bacterial infection. In the present work, LPS-derived 3-hydroxymyristate was extracted from plasma samples with an organic solvent, separated by reversed phase HPLC, and quantitated by MS/MS. This mass assay was combined with the limulus amebocyte lysate (LAL) bioassay to monitor neutralization of LPS activity in biological samples. The described HPLC/MS/MS method is a reliable, practical, accurate, and sensitive tool to quantitate LPS. The combination of the LAL and HPLC/MS/MS analyses provided new evidence for the intrinsic capacity of plasma lipoproteins and phospholipid transfer protein to neutralize the activity of LPS. In a subset of patients with systemic inflammatory response syndrome, with documented infection but with a negative plasma LAL test, significant amounts of LPS were measured by the HPLC/MS/MS method. Patients with the highest plasma LPS concentration were more severely ill. HPLC/MS/MS is a relevant method to quantitate endotoxin in a sample, to assess the efficacy of LPS neutralization, and to evaluate the proinflammatory potential of LPS in vivo. PMID:26023073

  20. Optimizing the function of upstanding activities in adult patients with acquired lesions of the central nervous system by using the Bobath concept approach - A case report.

    PubMed

    Jelica, Stjepan; Seper, Vesna; Davidović, Erna; Bujisić, Gordana

    2011-01-01

    Nonspecific medical gymnastic therapy may help patients after stroke achieve certain results in terms of efficiency but not in terms of quality of movement. The goal of treatment by Bobath concept is development of movement (effectiveness) and optimization of movement (efficiency). This article presents the case of a 62-year old patient who had experienced a stroke and has difficulties with standing up activities. It underscores the importance of not only recovery of function but also optimization of the function in such patients. PMID:21648353

  1. Temperature-Controlled Retinal Photocoagulation Reliably Generates Uniform Subvisible, Mild, or Moderate Lesions

    PubMed Central

    Koinzer, Stefan; Baade, Alexander; Schlott, Kerstin; Hesse, Carola; Caliebe, Amke; Roider, Johann; Brinkmann, Ralf

    2015-01-01

    Purpose Conventional retinal photocoagulation produces irregular lesions and does not allow reliable control of ophthalmoscopically invisible lesions. We applied automatically controlled retinal photocoagulation, which allows to apply uniform lesions without titration, and aimed at five different predictable lesion intensities in a study on rabbit eyes. Methods A conventional 532-nm photocoagulation laser was used in combination with a pulsed probe laser. They facilitated real-time fundus temperature measurements and automatic exposure time control for different predefined time/temperature dependent characteristics (TTC). We applied 225 control lesions (exposure time 200 ms) and 794 TTC lesions (5 intensities, exposure times 7–800 ms) in six rabbit eyes with variable laser power (20–66.4 mW). Starting after 2 hours, we examined fundus color and optical coherence tomographic (OCT) images over 3 months and classified lesion morphologies according to a seven-stage OCT classifier. Results Visibility rates in funduscopy (OCT) after 2 hours were 17% (68%) for TTC intensity group 1, 38% (90%) for TTC group 2 and greater than 94% (>98%) for all consecutive groups. TTC groups 1 through 4 correlated to increasing morphological lesion intensities and increasing median funduscopic and OCT diameters. Group 5 lesions were as large as, but more intense than group 4 lesions. Conclusions Automatic, temperature controlled photocoagulation allows to apply predictable subvisible, mild, or moderate lesions without manual power titration. Translational Relevance The technique will facilitate standardized, automatically controlled low and early treatment of diabetic retinopathy study (ETDRS) intensity photocoagulation independently of the treating physician, the treated eye and lesion location. PMID:26473086

  2. Pathology and MRI: exploring cognitive impairment in MS.

    PubMed

    Paul, F

    2016-09-01

    Cognitive impairment is a frequent symptom in people with multiple sclerosis, affecting up to 70% of patients. This article reviews the published association of cognitive dysfunction with neuroimaging findings. Cognitive impairment has been related to focal T2 hyperintense lesions, diffuse white matter damage and corical and deep gray matter atrophy. Focal lesions cannot sufficiently explain cognitive dysfunction in MS; microstructural tissue damage detectable by diffusion tensor imaging and gray matter atrophy are probably at least as relevant. Resting state functional magnetic resonance imaging is increasingly used to investigate the contribution of functional connectivity changes to cognitive function in MS. The fact that at least one third of MS patients are not overtly cognitively impaired despite significant radiographic tissue damage argues for protective factors (brain reserve, cognitive reserve) that require further clarification. It is concluded that the reported correlations between imaging findings and cognitive function do not imply causality. Well conceived and sufficiently powered longitudinal studies are lacking. Such studies would help unravel protective mechanisms against cogniitve decline and identify suitable imaging techniques to monitor cognitive function in individual patients with MS. PMID:27580903

  3. Non-locally regularized segmentation of multiple sclerosis lesion from multi-channel MRI data.

    PubMed

    Gao, Jingjing; Li, Chunming; Feng, Chaolu; Xie, Mei; Yin, Yilong; Davatzikos, Christos

    2014-10-01

    Segmentation of multiple sclerosis (MS) lesion is important for many neuroimaging studies. In this paper, we propose a novel algorithm for automatic segmentation of MS lesions from multi-channel MR images (T1W, T2W and FLAIR images). The proposed method is an extension of Li et al.'s algorithm in [1], which only segments the normal tissues from T1W images. The proposed method is aimed to segment MS lesions, while normal tissues are also segmented and bias field is estimated to handle intensity inhomogeneities in the images. Another contribution of this paper is the introduction of a nonlocal means technique to achieve spatially regularized segmentation, which overcomes the influence of noise. Experimental results have demonstrated the effectiveness and advantages of the proposed algorithm.

  4. Atmospheric identification of active ingredients in over-the-counter pharmaceuticals and drugs of abuse by atmospheric pressure glow discharge mass spectrometry (APGD-MS).

    PubMed

    Brewer, Tim M; Verkouteren, Jennifer R

    2011-09-15

    Atmospheric pressure glow discharge mass spectrometry was used to characterize the active ingredients in pharmaceutical over-the-counter (OTC) drug formulations (Tylenol Allergy, Alka-Seltzer Plus Nighttime, Sudafed, Aleve and Mucinex DM) and drugs of abuse (crack cocaine, methamphetamine, MDMA (ecstasy) and hydrocodone). Material was desorbed and directly ionized under atmospheric conditions by allowing the substance to come in direct contact with the plasma followed by mass spectrometric detection. With this technique, controlled substances and OTC medications were readily distinguished from one another. Characteristic mass spectra were identified for the active ingredients in the OTC and drugs of abuse. Importantly, all drug compounds studied here, both OTC and illicit, demonstrated signals for either molecular ions or protonated molecules as well as fragmentation patterns that are readily identified in the National Institute of Standards and Technology (NIST) electron ionization (EI) mass spectral library. It is believed that this technique holds promise for forensic and law enforcement communities for real-time atmospheric analysis of drugs with database-searchable spectra of controlled substances. PMID:21818799

  5. Innovative methodology to transfer conventional GC-MS heroin profiling to UHPLC-MS/MS.

    PubMed

    Debrus, B; Broséus, J; Guillarme, D; Lebrun, P; Hubert, P; Veuthey, J-L; Esseiva, P; Rudaz, S

    2011-03-01

    Nowadays, in forensic laboratories, heroin profiling is frequently carried out by gas chromatography coupled with mass spectrometry (GC-MS). This analytical technique is well established, provides good sensitivity and reproducibility, and allows the use of large databases. Despite those benefits, recently introduced analytical techniques, such as ultra-high-pressure liquid chromatography (UHPLC), could offer better chromatographic performance, which needs to be considered to increase the analysis throughput for heroin profiling. With the latter, chromatographic conditions were optimized through commercial modeling software and two atmospheric pressure ionization sources were evaluated. Data obtained from UHPLC-MS/MS were thus transferred, thanks to mathematical models to mimic GC-MS data. A calibration and a validation set of representative heroin samples were selected among the database to establish a transfer methodology and assess the models' abilities to transfer using principal component analysis and hierarchical classification analysis. These abilities were evaluated by computing the frequency of successful classification of UHPLC-MS/MS data among GC-MS database. Seven mathematical models were tested to adjust UHPLC-MS/MS data to GC-MS data. A simplified mathematical model was finally selected and offered a frequency of successful transfer equal to 95%.

  6. Relapsing-Remitting MS (RRMS)

    MedlinePlus

    ... pdf) Download Brochure Taming Stress (.pdf) Download Brochure Multiple Sclerosis and Your Emotions (.pdf) Download Brochure Disease Modifying Therapies Overview (.pdf) Download Document Pediatric MS Learn More ...

  7. Hydrogen Rearrangement Rules: Computational MS/MS Fragmentation and Structure Elucidation Using MS-FINDER Software.

    PubMed

    Tsugawa, Hiroshi; Kind, Tobias; Nakabayashi, Ryo; Yukihira, Daichi; Tanaka, Wataru; Cajka, Tomas; Saito, Kazuki; Fiehn, Oliver; Arita, Masanori

    2016-08-16

    Compound identification from accurate mass MS/MS spectra is a bottleneck for untargeted metabolomics. In this study, we propose nine rules of hydrogen rearrangement (HR) during bond cleavages in low-energy collision-induced dissociation (CID). These rules are based on the classic even-electron rule and cover heteroatoms and multistage fragmentation. We evaluated our HR rules by the statistics of MassBank MS/MS spectra in addition to enthalpy calculations, yielding three levels of computational MS/MS annotation: "resolved" (regular HR behavior following HR rules), "semiresolved" (irregular HR behavior), and "formula-assigned" (lacking structure assignment). With this nomenclature, 78.4% of a total of 18506 MS/MS fragment ions in the MassBank database and 84.8% of a total of 36370 MS/MS fragment ions in the GNPS database were (semi-) resolved by predicted bond cleavages. We also introduce the MS-FINDER software for structure elucidation. Molecular formulas of precursor ions are determined from accurate mass, isotope ratio, and product ion information. All isomer structures of the predicted formula are retrieved from metabolome databases, and MS/MS fragmentations are predicted in silico. The structures are ranked by a combined weighting score considering bond dissociation energies, mass accuracies, fragment linkages, and, most importantly, nine HR rules. The program was validated by its ability to correctly calculate molecular formulas with 98.0% accuracy for 5063 MassBank MS/MS records and to yield the correct structural isomer with 82.1% accuracy within the top-3 candidates. In a test with 936 manually identified spectra from an untargeted HILIC-QTOF MS data set of human plasma, formulas were correctly predicted in 90.4% of the cases, and the correct isomer structure was retrieved at 80.4% probability within the top-3 candidates, including for compounds that were absent in mass spectral libraries. The MS-FINDER software is freely available at http

  8. Hydrogen Rearrangement Rules: Computational MS/MS Fragmentation and Structure Elucidation Using MS-FINDER Software.

    PubMed

    Tsugawa, Hiroshi; Kind, Tobias; Nakabayashi, Ryo; Yukihira, Daichi; Tanaka, Wataru; Cajka, Tomas; Saito, Kazuki; Fiehn, Oliver; Arita, Masanori

    2016-08-16

    Compound identification from accurate mass MS/MS spectra is a bottleneck for untargeted metabolomics. In this study, we propose nine rules of hydrogen rearrangement (HR) during bond cleavages in low-energy collision-induced dissociation (CID). These rules are based on the classic even-electron rule and cover heteroatoms and multistage fragmentation. We evaluated our HR rules by the statistics of MassBank MS/MS spectra in addition to enthalpy calculations, yielding three levels of computational MS/MS annotation: "resolved" (regular HR behavior following HR rules), "semiresolved" (irregular HR behavior), and "formula-assigned" (lacking structure assignment). With this nomenclature, 78.4% of a total of 18506 MS/MS fragment ions in the MassBank database and 84.8% of a total of 36370 MS/MS fragment ions in the GNPS database were (semi-) resolved by predicted bond cleavages. We also introduce the MS-FINDER software for structure elucidation. Molecular formulas of precursor ions are determined from accurate mass, isotope ratio, and product ion information. All isomer structures of the predicted formula are retrieved from metabolome databases, and MS/MS fragmentations are predicted in silico. The structures are ranked by a combined weighting score considering bond dissociation energies, mass accuracies, fragment linkages, and, most importantly, nine HR rules. The program was validated by its ability to correctly calculate molecular formulas with 98.0% accuracy for 5063 MassBank MS/MS records and to yield the correct structural isomer with 82.1% accuracy within the top-3 candidates. In a test with 936 manually identified spectra from an untargeted HILIC-QTOF MS data set of human plasma, formulas were correctly predicted in 90.4% of the cases, and the correct isomer structure was retrieved at 80.4% probability within the top-3 candidates, including for compounds that were absent in mass spectral libraries. The MS-FINDER software is freely available at http://prime.psc.riken.jp/ .

  9. Contact allergy to oak moss: search for sensitizing molecules using combined bioassay-guided chemical fractionation, GC-MS, and structure-activity relationship analysis.

    PubMed

    Bernard, Guillaume; Giménez-Arnau, Elena; Rastogi, Suresh Chandra; Heydorn, Siri; Johansen, Jeanne Duus; Menné, Torkil; Goossens, An; Andersen, Klaus; Lepoittevin, Jean-Pierre

    2003-11-01

    In addition to pure synthetic fragrance materials several natural extracts are still in use in the perfume industry. Among them oak moss absolute, prepared from the lichen Evernia prunastri (L.) Arch., is considered a major contact sensitizer and is therefore included in the fragrance mix used for diagnosing perfume allergy. The process of preparing oak moss absolute has changed during recent years and, even though several potential sensitizers have been identified from former benzene extracts, its present constituents and their allergenic status are not clear. In the study reported here, we applied a method developed for the identification of contact allergens present in natural complex mixtures to oak moss absolute. The method is based on the combination of bioassay-guided chemical fractionation, gas chromatography-mass spectrometry analysis and structure-activity relationship studies. Our first results showed that atranol and chloroatranol, formed by transesterification and decarboxylation of the lichen depsides, atranorin and chloroatranorin, during the preparation of oak moss absolute, are strong elicitants in most patients sensitized to oak moss. Methyl-beta-orcinol carboxylate, a depside degradation product and the most important monoaryl derivative of oak moss from an olfactory standpoint, was also found to elicit a reaction in most patients.

  10. Contact allergy to oak moss: search for sensitizing molecules using combined bioassay-guided chemical fractionation, GC-MS, and structure-activity relationship analysis.

    PubMed

    Bernard, Guillaume; Giménez-Arnau, Elena; Rastogi, Suresh Chandra; Heydorn, Siri; Johansen, Jeanne Duus; Menné, Torkil; Goossens, An; Andersen, Klaus; Lepoittevin, Jean-Pierre

    2003-11-01

    In addition to pure synthetic fragrance materials several natural extracts are still in use in the perfume industry. Among them oak moss absolute, prepared from the lichen Evernia prunastri (L.) Arch., is considered a major contact sensitizer and is therefore included in the fragrance mix used for diagnosing perfume allergy. The process of preparing oak moss absolute has changed during recent years and, even though several potential sensitizers have been identified from former benzene extracts, its present constituents and their allergenic status are not clear. In the study reported here, we applied a method developed for the identification of contact allergens present in natural complex mixtures to oak moss absolute. The method is based on the combination of bioassay-guided chemical fractionation, gas chromatography-mass spectrometry analysis and structure-activity relationship studies. Our first results showed that atranol and chloroatranol, formed by transesterification and decarboxylation of the lichen depsides, atranorin and chloroatranorin, during the preparation of oak moss absolute, are strong elicitants in most patients sensitized to oak moss. Methyl-beta-orcinol carboxylate, a depside degradation product and the most important monoaryl derivative of oak moss from an olfactory standpoint, was also found to elicit a reaction in most patients. PMID:13680271

  11. Use of articulated registration for response assessment of individual metastatic bone lesions

    NASA Astrophysics Data System (ADS)

    Yip, Stephen; Jeraj, Robert

    2014-03-01

    Accurate skeleton registration is necessary to match corresponding metastatic bone lesions for response assessment over multiple scans. In articulated registration (ART), whole-body skeletons are registered by auto-segmenting individual bones, then rigidly aligning them. Performance and robustness of the ART in lesion matching were evaluated and compared to other commonly used registration techniques. Sixteen prostate cancer patients were treated either with molecular targeted therapy or chemotherapy. Ten out of the 16 patients underwent the double baseline whole-body [F-18]NaF PET/CT scans for test-retest (TRT) evaluation. Twelve of the 16 patients underwent pre- and mid-treatment [F-18]NaF PET/CT scans. Skeletons at different time points were registered using ART, rigid, and deformable (DR) registration algorithms. The corresponding lesions were contoured and identified on successive PET images based on including the voxels with the standardized uptake value over 15. Each algorithm was evaluated for its ability to accurately align corresponding lesions via skeleton registration. A lesion matching score (MS) was measured for each lesion, which quantified the per cent overlap between the lesion's two corresponding contours. Three separate sensitivity studies were conducted to investigate the robustness of ART in matching: sensitivity of lesion matching to various contouring threshold levels, effects of imperfections in the bone auto-segmentation and sensitivity of mis-registration. The performance of ART (MS = 82% for both datasets, p ≪ 0.001) in lesion matching was significantly better than rigid (MSTRT = 53%, MSResponse = 46%) and DR (MSTRT = 46%, MSResponse = 45%) algorithms. Neither varying threshold levels for lesion contouring nor imperfect bone segmentation had significant (p∼0.10) impact on the ART matching performance as the MS remained unchanged. Despite the mis-registration reduced MS for ART, as low as 67% (p ≪ 0.001), the performance remained to

  12. Characterizing the wake vortex signature for an active line of sight remote sensor. M.S. Thesis Technical Report No. 19

    NASA Technical Reports Server (NTRS)

    Heil, Robert Milton

    1994-01-01

    A recurring phenomenon, described as a wake vortex, develops as an aircraft approaches the runway to land. As the aircraft moves along the runway, each of the wing tips generates a spiraling and expanding cone of air. During the lifetime of this turbulent event, conditions exist over the runway which can be hazardous to following aircraft, particularly when a small aircraft is following a large aircraft. Left to themselves, these twin vortex patterns will converge toward each other near the center of the runway, harmlessly dissipating through interaction with each other or by contact with the ground. Unfortunately, the time necessary to disperse the vortex is often not predictable, and at busy airports can severely impact terminal area productivity. Rudimentary methods of avoidance are in place. Generally, time delays between landing aircraft are based on what is required to protect a small aircraft. Existing ambient wind conditions can complicate the situation. Reliable detection and tracking of a wake vortex hazard is a major technical problem which can significantly impact runway productivity. Landing minimums could be determined on the basis of the actual hazard rather than imposed on the basis of a worst case scenario. This work focuses on using a windfield description of a wake vortex to generate line-of-sight Doppler velocity truth data appropriate to an arbitrarily located active sensor such as a high resolution radar or lidar. The goal is to isolate a range Doppler signature of the vortex phenomenon that can be used to improve detection. Results are presented based on use of a simplified model of a wake vortex pattern. However, it is important to note that the method of analysis can easily be applied to any vortex model used to generate a windfield snapshot. Results involving several scan strategies are shown for a point sensor with a range resolution of 1 to 4 meters. Vortex signatures presented appear to offer potential for detection and tracking.

  13. Voxelwise Bayesian Lesion Deficit Analysis

    PubMed Central

    Chen, Rong; Hillis, Argye E.; Pawlak, Mikolaj; Herskovits, Edward H

    2008-01-01

    Relating cognitive deficits to the presence of lesions has been an important means of delineating structure-function associations in the human brain. We propose a voxel-based Bayesian method for lesion-deficit analysis, which identifies complex linear or nonlinear associations among brain-lesion locations, and neurological status. We validated this method using a simulated data set, and we applied this algorithm to data obtained from an acute-stroke study to identify associations among voxels with infarct or hypoperfusion, and impaired word reading. We found that a distributed region involving Brodmann areas (BA) 22, 37, 39, and 40 was implicated in word reading. PMID:18328733

  14. No Carious Cervical Lesions: Abfraction

    PubMed Central

    Shetty, Sumanth M; Shetty, Rashmi G; Mattigatti, Sudha; Managoli, Noopur A; Rairam, Surabhi G; Patil, Ashwini M

    2013-01-01

    Abfraction or Theory of Abfraction is a theory explaining the non-carious cervical lesions (NCCL). It suggests that they are caused by flexural forces, usually from cyclic loading; the enamel, especially at the cementoenamel junction (CEJ), undergoes this pattern of destruction by separating the enamel rods. Clinical aspect importance of these ineart lesions are at most important to be detected for early intervention and treatment modalities as options during the progression of the disease. How to cite this article: Shetty SM, Shetty RG, Mattigatti S, Managoli NA, Rairam SG, Patil AM. No Carious Cervical Lesions: Abfraction. J Int Oral Health 2013; 5(5):142-5. PMID:24324319

  15. Analysis of acrylamide by LC-MS/MS and GC-MS in processed Japanese foods.

    PubMed

    Ono, H; Chuda, Y; Ohnishi-Kameyama, M; Yada, H; Ishizaka, M; Kobayashi, H; Yoshida, M

    2003-03-01

    Acrylamide concentrations in processed foods (63 samples covering 31 product types) from Japan were analysed by LC-MS/MS and GC-MS methods. The limit of detection and limit of quantification of acrylamide were 0.2 ng x ml(-1) (6 fmol) and 0.8 ng x ml(-1) (22 fmol), respectively, by LC-MS/MS, and those of 2,3-dibromopropionamide derived from acrylamide were 12 ng x ml(-1) (52 fmol) and 40 ng x ml(-1) (170 fmol), respectively, by GC-MS. Repeatability given as RSD was <5 and <15% for the LC-MS/MS and GC-MS methods, respectively. High correlation (r(2) - 0.946) was observed between values obtained by the two methods. Most potato crisps and whole potato-based fried snacks showed acrylamide concentrations >1000 microg x kg(-1). The concentrations in non-whole potato-based snacks, rice crackers processed by grilling or frying, and candied sweet potatoes were lower compared with those in the potato crisps and the whole potato-based fried snacks. One of the whole potato-based fried snacks, however, showed low acrylamide concentration (<50 microg x kg(-1)) suggesting the formation of acrylamide is strongly influenced by processing conditions. Acrylamide concentrations in instant precooked noodles and won-tons were <100 microg x kg(-1) with only one exception. Roasted barley grains for 'Mugi-cha' tea contained 200-600 microg x kg(-1) acrylamide.

  16. Improvements in Memory after Medial Septum Stimulation Are Associated with Changes in Hippocampal Cholinergic Activity and Neurogenesis

    PubMed Central

    Jeong, Da Un; Lee, Ji Eun; Lee, Sung Eun; Chang, Won Seok; Kim, Sung June; Chang, Jin Woo

    2014-01-01

    Deep brain stimulation (DBS) has been found to have therapeutic effects in patients with dementia, but DBS mechanisms remain elusive. To provide evidence for the effectiveness of DBS as a treatment for dementia, we performed DBS in a rat model of dementia with intracerebroventricular administration of 192 IgG-saporins. We utilized four groups of rats, group 1, unlesioned control; group 2, cholinergic lesion; group 3, cholinergic lesion plus medial septum (MS) electrode implantation (sham stimulation); group 4, cholinergic lesions plus MS electrode implantation and stimulation. During the probe test in the water maze, performance of the lesion group decreased for measures of time spent and the number of swim crossings over the previous platform location. Interestingly, the stimulation group showed an equivalent performance to the normal group on all measures. And these are partially reversed by the electrode implantation. Acetylcholinesterase activity in the hippocampus was decreased in lesion and implantation groups, whereas activity in the stimulation group was not different from the normal group. Hippocampal neurogenesis was increased in the stimulation group. Our results revealed that DBS of MS restores spatial memory after damage to cholinergic neurons. This effect is associated with an increase in hippocampal cholinergic activity and neurogenesis. PMID:25101288

  17. Active symptom control with or without chemotherapy in the treatment of patients with malignant pleural mesothelioma (MS01): a multicentre randomised trial

    PubMed Central

    Muers, Martin F; Stephens, Richard J; Fisher, Patricia; Darlison, Liz; Higgs, Christopher MB; Lowry, Erica; Nicholson, Andrew G; O'Brien, Mary; Peake, Michael; Rudd, Robin; Snee, Michael; Steele, Jeremy; Girling, David J; Nankivell, Matthew; Pugh, Cheryl; Parmar, Mahesh KB

    2008-01-01

    Summary Background Malignant pleural mesothelioma is almost always fatal, and few treatment options are available. Although active symptom control (ASC) has been recommended for the management of this disease, no consensus exists for the role of chemotherapy. We investigated whether the addition of chemotherapy to ASC improved survival and quality of life. Methods 409 patients with malignant pleural mesothelioma, from 76 centres in the UK and two in Australia, were randomly assigned to ASC alone (treatment could include steroids, analgesic drugs, bronchodilators, palliative radiotherapy [n=136]); to ASC plus MVP (four cycles of mitomycin 6 mg/m2, vinblastine 6 mg/m2, and cisplatin 50 mg/m2 every 3 weeks [n=137]); or to ASC plus vinorelbine (one injection of vinorelbine 30 mg/m2 every week for 12 weeks [n=136]). Randomisation was done by minimisation, with stratification for WHO performance status, histology, and centre. Follow-up was every 3 weeks to 21 weeks after randomisation, and every 8 weeks thereafter. Because of slow accrual, the two chemotherapy groups were combined and compared with ASC alone for the primary outcome of overall survival. Analysis was by intention to treat. This study is registered, number ISRCTN54469112. Findings At the time of analysis, 393 (96%) patients had died (ASC 132 [97%], ASC plus MVP 132 [96%], ASC plus vinorelbine 129 [95%]). Compared with ASC alone, we noted a small, non-significant survival benefit for ASC plus chemotherapy (hazard ratio [HR] 0·89 [95% CI 0·72–1·10]; p=0·29). Median survival was 7·6 months in the ASC alone group and 8·5 months in the ASC plus chemotherapy group. Exploratory analyses suggested a survival advantage for ASC plus vinorelbine compared with ASC alone (HR 0·80 [0·63–1·02]; p=0·08), with a median survival of 9·5 months. There was no evidence of a survival benefit with ASC plus MVP (HR 0·99 [0·78–1·27]; p=0·95). We observed no between-group differences in four predefined quality

  18. Determination of Glyphosate Levels in Breast Milk Samples from Germany by LC-MS/MS and GC-MS/MS.

    PubMed

    Steinborn, Angelika; Alder, Lutz; Michalski, Britta; Zomer, Paul; Bendig, Paul; Martinez, Sandra Aleson; Mol, Hans G J; Class, Thomas J; Pinheiro, Nathalie Costa

    2016-02-17

    This study describes the validation and application of two independent analytical methods for the determination of glyphosate in breast milk. They are based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) and gas chromatography-tandem mass spectrometry (GC-MS/MS), respectively. For LC-MS/MS, sample preparation involved an ultrafiltration followed by chromatography on an anion exchange column. The analysis by GC-MS/MS involved an extraction step, cleanup on a cation exchange column, and derivatization with heptafluorobutanol and trifluoroacetic acid anhydride. Both methods were newly developed for breast milk and are able to quantify glyphosate residues at concentrations as low as 1 ng/mL. The methods were applied to quantify glyphosate levels in 114 breast milk samples, which had been collected from August to September of 2015 in Germany. The mothers participated at their own request and thus do not form a representative sample. In none of the investigated samples were glyphosate residues above the limit of detection found.

  19. Analysis of geometrical relations between multiple sclerosis lesions and brain vasculature

    NASA Astrophysics Data System (ADS)

    Kozinska, Dorota E.; Holland, Christopher; Krissian, Karl; Westin, Carl-Fredrik; Guttmann, Charles R. G.

    2004-04-01

    Due to histological evidence of the fundamental role of the cerebral vessels in white matter abnormalities, recently there has been an increased interest in analyzing the relationship between brain white matter lesions in multiple sclerosis (MS) and brain vasculature. We developed a method for visualization and measurement of geometrical relationships between MS lesions and the brain vessels imaged with magnetic resonance (MR) imaging techniques. Using MR images we create surface models of lesions and vessels that constitute a base for quantitative analysis. In this work we analyze correlation between basic lesion geometrical characteristics and two features: 1) distances to vessels, and 2) vessel caliber. For the former, we compute a distance map from the vessel structure, such that each voxel stores its distance vector to the closest vessel. This allows the measurements of Euclidean distances to the closest vessels. For the latter, we compute a radius map in which each voxel stores the radius of its closest vessel. It is used to measure distribution of lesions with respect to the vessel caliber. We compute and analyze relations between the basic geometrical characteristics of lesions and the closest vessels locations and calibers. To demonstrate the feasibility of the developed technique we present results from the study of 3 MS cases.

  20. Electrocautery for Precancerous Anal Lesions

    Cancer.gov

    Results from a randomized clinical trial conducted in Amsterdam suggest that electrocautery is better than topical imiquimod or fluorouracil at treating potentially precancerous anal lesions in HIV-positive men who have sex with men.

  1. Gram stain of skin lesion

    MedlinePlus

    ... may be done along with this test. Other studies are often done on a skin sample to determine if cancer is present. Viral skin lesions like herpes simplex are examined by other tests or a viral culture.

  2. Osteochondral Lesions of Major Joints

    PubMed Central

    Durur-Subasi, Irmak; Durur-Karakaya, Afak; Yildirim, Omer Selim

    2015-01-01

    This paper provides information about osteochondral lesions (OCL) and example cases of OCL occurring in major joints, some of which are rarely seen. This simple tutorial is presented in question and answer format. PMID:26180500

  3. Neuronal activity regulates remyelination via glutamate signalling to oligodendrocyte progenitors

    PubMed Central

    Gautier, Hélène O. B.; Evans, Kimberley A.; Volbracht, Katrin; James, Rachel; Sitnikov, Sergey; Lundgaard, Iben; James, Fiona; Lao-Peregrin, Cristina; Reynolds, Richard; Franklin, Robin J. M.; Káradóttir, Ragnhildur T

    2015-01-01

    Myelin regeneration can occur spontaneously in demyelinating diseases such as multiple sclerosis (MS). However, the underlying mechanisms and causes of its frequent failure remain incompletely understood. Here we show, using an in-vivo remyelination model, that demyelinated axons are electrically active and generate de novo synapses with recruited oligodendrocyte progenitor cells (OPCs), which, early after lesion induction, sense neuronal activity by expressing AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)/kainate receptors. Blocking neuronal activity, axonal vesicular release or AMPA receptors in demyelinated lesions results in reduced remyelination. In the absence of neuronal activity there is a ∼6-fold increase in OPC number within the lesions and a reduced proportion of differentiated oligodendrocytes. These findings reveal that neuronal activity and release of glutamate instruct OPCs to differentiate into new myelinating oligodendrocytes that recover lost function. Co-localization of OPCs with the presynaptic protein VGluT2 in MS lesions implies that this mechanism may provide novel targets to therapeutically enhance remyelination. PMID:26439639

  4. GC/MS profiling, in vitro anti-leptospiral and haemolytic activities of Boesenbergia rotunda (L.) Mansf. used as a medicinal plant by Nicobarese of Andaman and Nicobar Islands.

    PubMed

    Chander, M Punnam; Vinod Kumar, K; Lall, Chandan; Vimal Raj, R; Vijayachari, P

    2016-01-01

    Leaves of the plant Boesenbergia rotunda are used by the Nicobarese tribe of Andaman and Nicobar Islands, India, to prepare traditional medicine for treating fever, headache and body ache. In the present investigation, methanol fraction of these leaves were analysed by GC/MS that revealed the presence of 25 compounds. The anti-leptospiral activity of methanol crude extract was determined by both microdilution and macrodilution methods. The MICs of the extract were tested against 24 pathogenic leptospiral strains and ranged between 62.5-125 μg/mL in both microdilution and macrodilution. The range of MBCs was 250 and 500 μg/mL in macrodilution and microdilution respectively. The crude extract was subjected to cytotoxic studies and found to have negligible or no haemolytic activity, exhibiting IC50 values of greater than 4 mg/mL. Further in vivo studies are needed to investigate the pharmacological and toxicological properties of Boesenbergia rotunda, before it can be considered as a new anti-leptospiral agent. PMID:26114982

  5. Kappa opioid receptor activation alleviates experimental autoimmune encephalomyelitis and promotes oligodendrocyte-mediated remyelination.

    PubMed

    Du, Changsheng; Duan, Yanhui; Wei, Wei; Cai, Yingying; Chai, Hui; Lv, Jie; Du, Xiling; Zhu, Jian; Xie, Xin

    2016-01-01

    Multiple sclerosis (MS) is characterized by autoimmune damage to the central nervous system. All the current drugs for MS target the immune system. Although effective in reducing new lesions, they have limited effects in preventing the progression of disability. Promoting oligodendrocyte-mediated remyelination and recovery of neurons are the new directions of MS therapy. The endogenous opioid system, consisting of MOR, DOR, KOR and their ligands, has been suggested to participate in the pathogenesis of MS. However, the exact receptor and mechanism remain elusive. Here we show that genetic deletion of KOR exacerbates experimental autoimmune encephalomyelitis, whereas activating KOR with agonists alleviates the symptoms. KOR does not affect immune cell differentiation and function. Instead, it promotes oligodendrocyte differentiation and myelination both in vitro and in vivo. Our study suggests that targeting KOR might be an intriguing way to develop new MS therapies that may complement the existing immunosuppressive approaches.

  6. Kappa opioid receptor activation alleviates experimental autoimmune encephalomyelitis and promotes oligodendrocyte-mediated remyelination

    PubMed Central

    Du, Changsheng; Duan, Yanhui; Wei, Wei; Cai, Yingying; Chai, Hui; Lv, Jie; Du, Xiling; Zhu, Jian; Xie, Xin

    2016-01-01

    Multiple sclerosis (MS) is characterized by autoimmune damage to the central nervous system. All the current drugs for MS target the immune system. Although effective in reducing new lesions, they have limited effects in preventing the progression of disability. Promoting oligodendrocyte-mediated remyelination and recovery of neurons are the new directions of MS therapy. The endogenous opioid system, consisting of MOR, DOR, KOR and their ligands, has been suggested to participate in the pathogenesis of MS. However, the exact receptor and mechanism remain elusive. Here we show that genetic deletion of KOR exacerbates experimental autoimmune encephalomyelitis, whereas activating KOR with agonists alleviates the symptoms. KOR does not affect immune cell differentiation and function. Instead, it promotes oligodendrocyte differentiation and myelination both in vitro and in vivo. Our study suggests that targeting KOR might be an intriguing way to develop new MS therapies that may complement the existing immunosuppressive approaches. PMID:27040771

  7. Kappa opioid receptor activation alleviates experimental autoimmune encephalomyelitis and promotes oligodendrocyte-mediated remyelination.

    PubMed

    Du, Changsheng; Duan, Yanhui; Wei, Wei; Cai, Yingying; Chai, Hui; Lv, Jie; Du, Xiling; Zhu, Jian; Xie, Xin

    2016-01-01

    Multiple sclerosis (MS) is characterized by autoimmune damage to the central nervous system. All the current drugs for MS target the immune system. Although effective in reducing new lesions, they have limited effects in preventing the progression of disability. Promoting oligodendrocyte-mediated remyelination and recovery of neurons are the new directions of MS therapy. The endogenous opioid system, consisting of MOR, DOR, KOR and their ligands, has been suggested to participate in the pathogenesis of MS. However, the exact receptor and mechanism remain elusive. Here we show that genetic deletion of KOR exacerbates experimental autoimmune encephalomyelitis, whereas activating KOR with agonists alleviates the symptoms. KOR does not affect immune cell differentiation and function. Instead, it promotes oligodendrocyte differentiation and myelination both in vitro and in vivo. Our study suggests that targeting KOR might be an intriguing way to develop new MS therapies that may complement the existing immunosuppressive approaches. PMID:27040771

  8. LIMD2 Is a Small LIM-Only Protein Overexpressed in Metastatic Lesions That Regulates Cell Motility and Tumor Progression by Directly Binding to and Activating the Integrin-Linked Kinase

    PubMed Central

    Osborne, Michael J.; Prokop, Jeremy W.; McDonald, Paul C.; Karar, Jayashree; Hou, Zhaoyuan; He, Mei; Kebebew, Electron; Orntoft, Torben; Herlyn, Meenhard; Caton, Andrew J.; Fredericks, William; Malkowicz, Bruce; Paterno, Christopher S.; Carolin, Alexandra S.; Speicher, David W.; Skordalakes, Emmanuel; Huang, Qihong; Dedhar, Shoukat; Borden, Katherine L.B.; Rauscher, Frank J.

    2014-01-01

    Proteins that communicate signals from the cytoskeleton to the nucleus are prime targets for effectors of metastasis as they often transduce signals regulating adhesion, motility, and invasiveness. LIM domain proteins shuttle between the cytoplasm and the nucleus, and bind to partners in both compartments, often coupling changes in gene expression to extracellular cues. In this work, we characterize LIMD2, a mechanistically undefined LIM-only protein originally found to be overexpressed in metastatic lesions but absent in the matched primary tumor. LIMD2 levels in fresh and archival tumors positively correlate with cell motility, metastatic potential, and grade, including bladder, melanoma, breast, and thyroid tumors. LIMD2 directly contributes to these cellular phenotypes as shown by overexpression, knockdown, and reconstitution experiments in cell culture models. The solution structure of LIMD2 that was determined using nuclear magnetic resonance revealed a classic LIM-domain structure that was highly related to LIM1 of PINCH1, a core component of the integrin-linked kinase–parvin–pinch complex. Structural and biochemical analyses revealed that LIMD2 bound directly to the kinase domain of integrin-linked kinase (ILK) near the active site and strongly activated ILK kinase activity. Cells that were null for ILK failed to respond to the induction of invasion by LIMD2. This strongly suggests that LIMD2 potentiates its biologic effects through direct interactions with ILK, a signal transduction pathway firmly linked to cell motility and invasion. In summary, LIMD2 is a new component of the signal transduction cascade that links integrin-mediated signaling to cell motility/metastatic behavior and may be a promising target for controlling tumor spread. PMID:24590809

  9. Asterixis in focal brain lesions.

    PubMed

    Degos, J D; Verroust, J; Bouchareine, A; Serdaru, M; Barbizet, J

    1979-11-01

    Asterixis was observed in 20 cases of focal brain lesions. Metabolic or toxic factors were excluded. An electromyogram study of asterixis was carried out in nine cases to establish the diagnosis. The site of the focal lesion was either parietal or mesencephalic and was always contralateral to the asterixis. "Focal asterixis" could result from a dysfunction of the sensorimotor integration in the parietal lobe and the midbrain.

  10. Benign Pediatric Salivary Gland Lesions.

    PubMed

    Carlson, Eric R; Ord, Robert A

    2016-02-01

    Salivary gland lesions are rare in pediatric patients. In addition, the types of salivary gland tumors are different in their distribution in specific sites in the major and minor salivary glands in children compared with adults. This article reviews benign neoplastic and nonneoplastic salivary gland disorders in pediatric patients to help clinicians to develop an orderly differential diagnosis that will lead to expedient treatment of pediatric patients with salivary gland lesions.

  11. Endoscopic Management of Dieulafoy's Lesion

    PubMed Central

    Jeon, Hye Kyung

    2015-01-01

    A Dieulafoy's lesion is a vascular abnormality consisting of a large caliber-persistent tortuous submucosal artery. A small mucosal defect with the eruption of this protruding vessel can cause bleeding. In fact, a Dieulafoy's lesion is a relatively rare but potentially life-threatening condition. It accounts for 1% to 2% of cases of acute gastrointestinal bleeding. Although there is no consensus on the treatment of Dieulafoy's lesions; treatment options depend on the mode of presentation, site of the lesion, and available expertise. Endoscopic therapy is usually successful in achieving primary hemostasis, with hemostasis success rates reaching 75% to 100%. Although various therapeutic endoscopic methods are used to control bleeding in Dieulafoy's lesions, the best method for endoscopic intervention is not clear. Combination endoscopic therapy is known to be superior to monotherapy because of a lower rate of recurrent bleeding. In addition, mechanical therapies including hemostatic clipping and endoscopic band ligation are more effective and successful in controlling bleeding than other endoscopic methods. Advances in endoscopic techniques have reduced mortality in patients with Dieulafoy's lesion-from 80% to 8%-and consequently, the need for surgical intervention has been reduced. Currently, surgical intervention is used for cases that fail therapeutic endoscopic or angiographic interventions. PMID:25844338

  12. DNA lesions: A thermodynamic perspective

    SciTech Connect

    Plum, G.E.; Breslauer, K.J.

    1994-12-31

    The studies described in this paper are part of an overall program project entitled {open_quotes}The Chemistry and Biology of Exocyclic DNA Adducts and Oxidative DNA Damage.{close_quotes}. Initially, all the project leaders discuss and agree on biologically interesting lesions to target for study. Then begins the process of developing the chemistry required to synthesize modified nucleosides that either correspond to or model the damage sites of interest. Such modified nucleotides then are incorporated into oligonucleotides that are hybridized to their complements, thereby forming lesion-containing duplex structures. In any given duplex, the identity of the lesion-opposing nucleoside on the complementary strand is systematically altered, thereby allowing us to evaluate the impact on duplex properties of the identity of the base opposite the lesion. For comparative purposes, the undamaged parent Watson-Crick duplex also is synthesized. Such families of DNA duplexes are then sent for independent physiochemical characterizations. Armed with an extensive body of biophysical data, one then searches for correlations between the physiochemical influences of the lesions on duplex properties and the biological consequences of each lesion. At this stage, our approach is highly empirical. Ultimately, we hope that our studies will reveal correlations between physiochemical properties and biological consequences such that we will develop predictive powers and gain insight into the mechanisms of recognition, repair, and mutagenesis.

  13. Simulation of spiculated breast lesions

    NASA Astrophysics Data System (ADS)

    Elangovan, Premkumar; Alrehily, Faisal; Pinto, R. Ferrari; Rashidnasab, Alaleh; Dance, David R.; Young, Kenneth C.; Wells, Kevin

    2016-03-01

    Virtual clinical trials are a promising new approach increasingly used for the evaluation and comparison of breast imaging modalities. A key component in such an assessment paradigm is the use of simulated pathology, in particular, simulation of lesions. Breast mass lesions can be generally classified into two categories based on their appearance; nonspiculated masses and spiculated masses. In our previous work, we have successfully simulated non-spiculated masses using a fractal growth process known as diffusion limited aggregation. In this new work, we have extended the DLA model to simulate spiculated lesions by using features extracted from patient DBT images containing spiculated lesions. The features extracted included spicule length, width, curvature and distribution. This information was used to simulate realistic looking spicules which were attached to the surface of a DLA mass to produce a spiculated mass. A batch of simulated spiculated masses was inserted into normal patient images and presented to an experienced radiologist for review. The study yielded promising results with the radiologist rating 60% of simulated lesions in 2D and 50% of simulated lesions in DBT as realistic.

  14. Lesion comparison of multiple sclerosis in hispanic and caucasian patients utilizing an imaging informatics-based eFolder system

    NASA Astrophysics Data System (ADS)

    Ma, Kevin; Fernandez, James; Amezcua, Lilyana; Lerner, Alex; Shiroishi, Mark; Liu, Brent

    2012-02-01

    Multiple sclerosis (MS) is a demyelinating disease in the central nervous system. Genetics have been considered as a leading factor in the prevalence and disease course of MS. We have presented an informatics-based eFolder system for integrating patients' clinical data with MR images and lesion quantification results. The completed eFolder system has been designed and developed in aiding to evaluate disease manifestation differences in Hispanic and Caucasian MS patients. MS lesion data, as shown in MRI, can be extracted by the 3-D automatic lesion detection tool in the eFolder, and data storing and mining tools in eFolder is able to extract and compare data from individual patients. The computer-aided detection (CAD) algorithm has been modified and enhanced to include spatial information as detection criteria. For this study, 36 Caucasian MS patients and 36 matched Hispanic patients have been selected. Most recent MR images of the patients are collected, and images are evaluated both by the CAD tool in the eFolder and radiologists. The results are compared between Caucasian and Hispanic patients and statistically evaluated to see if the two populations have significant difference in lesion presentations. The results can be used to evaluate differences in the two groups of patients and to evaluate the new CAD algorithm's performance with radiologists' contours. Significant findings can further evaluate effectiveness of MS eFolder in MS-related research.

  15. GeLC-MS/MS Analysis of Complex Protein Mixtures

    PubMed Central

    Dzieciatkowska, Monika; Hill, Ryan; Hansen, Kirk C.

    2015-01-01

    Discovery-based proteomics has found its place in nearly every facet of biological research. A key objective of this approach is to maximize sequence coverage for proteins across a wide concentration range. Fractionating samples at the protein level is one of the most common ways to circumvent challenges due to sample complexity and improve proteome coverage. Of the available methods, one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by liquid chromatography-tandem mass spectrometry (GeLC-MS/MS) is a robust and reproducible method for qualitative and quantitative proteomic analysis. Here we describe a general GeLC-MS/MS protocol and include technical advice and outline caveats to increase the probability of a successful analysis. PMID:24791981

  16. METLIN: MS/MS metabolite data from the MAGGIE Project

    DOE Data Explorer

    METLIN is a metabolite database for metabolomics containing over 50,000 structures, it also represents a data management system designed to assist in a broad array of metabolite research and metabolite identification by providing public access to its repository of current and comprehensive MS/MS metabolite data. An annotated list of known metabolites and their mass, chemical formula, and structure are available on the METLIN website. Each metabolite is conveniently linked to outside resources such as the the Kyoto Encyclopedia of Genes and Genomes (KEGG) for further reference and inquiry. MS/MS data is also available on many of the metabolites. The list is expanding continuously as more metabolite information is being deposited and discovered. [from http://metlin.scripps.edu/] Metlin is a component of the MAGGIE Project. MAGGIE is funded by the DOE Genomics: GTL and is an acronym for "Molecular Assemblies, Genes, and Genomics Integrated Efficiently."

  17. Automated detection and quantification of multiple sclerosis lesions in MR volumes of the brain

    NASA Astrophysics Data System (ADS)

    Mitchell, Ross; Karlik, Stephen J.; Lee, Donald H.; Fenster, Aaron

    1992-06-01

    MRI is the principle technique for the diagnosis of multiple sclerosis. However, manually quantifying the number and extent of lesions in MR images is arduous. Therefore, we are developing a computerized 3-D quantitative system to determine the lesions' extent and their changes in time. Our system uses proton density (PD) and T2 weighted MR volumes. A 2-D histogram showing the frequency of voxels with particular PD and T2 weighted intensities reveals that white matter, grey matter (GM), and cerebro-spinal fluid voxels correspond to distinct clusters in this histogram and can be classified on this basis. However, many true MS lesion voxels have PD and T2 weighted intensities similar to GM. Therefore, on the basis of location in the histogram alone, it is difficult to differentiate all lesions voxels from GM voxels. However, some lesions have a distinctive `peak' in the 2-D histogram which can be used to identify them successfully. Using this system it is possible to assess and monitor changes in time for these lesions. To demonstrate this ability, four MR examinations of a single chronic-progressive MS patient obtained over a 510 day period were analyzed using our system. Three-dimensional volume rendering and measurement of the results clearly shows changes in lesion shape, position, and size.

  18. Qualitative identification of rodenticide anticoagulants by LC-MS/MS.

    PubMed

    Middleberg, Robert A; Homan, Joseph

    2012-01-01

    Rodenticide anticoagulants are used in the control of rodent populations. In addition to accidental ingestions in humans, such agents have also been used for homicidal and suicidal purposes. There are two major groups of rodenticide anticoagulants - hydroxycoumarins and indanediones. Before the advent of LC-MS/MS, analysis for such agents was relegated to such techniques as TLC and HPLC with nonspecific modes of detection. LC-MS/MS has been used to determine any given number of rodenticide anticoagulants in animal tissues, foods, plasma, etc. Use of this technique allows for the simultaneous identification of individual compounds within both classes of rodenticide anticoagulants. The LC-MS/MS method presented allows for simultaneous qualitative identification of brodifacoum, bromadiolone, chlorphacinone, dicumarol, difenacoum, diphacinone, and warfarin in blood, serum, and plasma using ESI in the negative mode. Two transitions are monitored for each analyte after a simple sample preparation. Chromatographic separation is accomplished using a gradient of ammonium hydroxide in water and ammonium hydroxide in methanol. Chloro-warfarin is used as internal standard. PMID:22767114

  19. No association of tobacco use and disease activity in multiple sclerosis

    PubMed Central

    Myhr, Kjell-Morten; Holmøy, Trygve; Benth, Jūratė Šaltytė; Løken-Amsrud, Kristin I.; Wergeland, Stig; Beiske, Antonie G.; Bjerve, Kristian S.; Hovdal, Harald; Lilleås, Finn; Midgard, Rune; Pedersen, Tom; Bakke, Søren J.; Torkildsen, Øivind

    2016-01-01

    Objective: To study whether tobacco use is associated with MRI and clinical disease activity in patients with multiple sclerosis (MS). Methods: Prospective cohort study of 87 patients with relapsing-remitting MS originally included in a randomized placebo-controlled trial of omega-3 fatty acids in MS (the OFAMS Study). Serum levels of cotinine (biomarker of tobacco use) were analyzed at baseline and every 6 months for 2 years. MRI activity was assessed at baseline and monthly for 9 months and after 12 and 24 months. Results: Fifty-three patients (61%) had serum cotinine levels ≥85 nmol/L on ≥60% of the measurements and were considered tobacco users and 34 (39%) had cotinine levels <85 nmol/L, consistent with non–tobacco use. There was no association between tobacco use and the occurrence of new gadolinium-enhancing T1 lesions, new or enlarging T2 lesions, or their aggregate (combined unique activity). Furthermore, there was no association between cotinine levels and MRI activity for the tobacco users, and tobacco users did not have more relapses or Expanded Disability Status Scale progression. Conclusion: Our results indicate that tobacco use does not directly influence MRI activity or relapse rate in MS. This may implicate that the reported association between smoking and MS disease progression could be mediated through other mechanisms. PMID:27458599

  20. Association between phospholipase production by Malassezia pachydermatis and skin lesions.

    PubMed

    Cafarchia, C; Otranto, D

    2004-10-01

    An evaluation was made of the phospholipase activities of Malassezia pachydermatis strains isolated from healthy dogs versus those from dogs with dermatitis and otitis. A high percentage of strains of M. pachydermatis obtained from lesion sites (93.9%) produced phospholipase, compared to the strains obtained from healthy skin of the same dog with localized lesions (41.4%) and healthy dogs (10.6%). PMID:15472366

  1. STS-54 MS2 Harbaugh and MS3 Helms during training in JSC's ETA / airlock

    NASA Technical Reports Server (NTRS)

    1992-01-01

    STS-54 Endeavour, Orbiter Vehicle (OV) 105, Mission Specialist (MS2) Gregory J. Harbaugh, wearing an extravehicular mobility unit (EMU) and communications carrier assembly (CCA), is assisted by MS3 Susan J. Helms during Environmental Test Article (ETA) / Airlock training (STB-SS-956) in JSC's Crew Systems Laboratory Bldg 7. Helms readies the EMU glove as Harbaugh looks on. Though not assigned to the scheduled STS-54 extravehicular activity (EVA), Helms will assist Harbaugh in EVA preparations as she does here and will serve as a backup EVA crewmember. Two crewmembers will perform a four-hour-plus spacewalk during STS-54.

  2. PS-OCT of natural pigmented and nonpigmented interproximal caries lesions

    NASA Astrophysics Data System (ADS)

    Ngaotheppitak, Patara; Darling, Cynthia L.; Fried, Daniel

    2005-03-01

    Previous studies have demonstrated that Polarization Sensitive Optical Coherence Tomography (PS-OCT) can be used to image early dental caries. The purpose of this study was to compare the measured reflectivity of natural caries lesions with the mineral loss measured using digital microradiography. An all polarization-maintaining fiber based PS-OCT system operating at 1310-nm was used to acquire polariza