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Sample records for early vascular response

  1. Stomatal Blue Light Response Is Present in Early Vascular Plants.

    Science.gov (United States)

    Doi, Michio; Kitagawa, Yuki; Shimazaki, Ken-ichiro

    2015-10-01

    Light is a major environmental factor required for stomatal opening. Blue light (BL) induces stomatal opening in higher plants as a signal under the photosynthetic active radiation. The stomatal BL response is not present in the fern species of Polypodiopsida. The acquisition of a stomatal BL response might provide competitive advantages in both the uptake of CO2 and prevention of water loss with the ability to rapidly open and close stomata. We surveyed the stomatal opening in response to strong red light (RL) and weak BL under the RL with gas exchange technique in a diverse selection of plant species from euphyllophytes, including spermatophytes and monilophytes, to lycophytes. We showed the presence of RL-induced stomatal opening in most of these species and found that the BL responses operated in all euphyllophytes except Polypodiopsida. We also confirmed that the stomatal opening in lycophytes, the early vascular plants, is driven by plasma membrane proton-translocating adenosine triphosphatase and K(+) accumulation in guard cells, which is the same mechanism operating in stomata of angiosperms. These results suggest that the early vascular plants respond to both RL and BL and actively regulate stomatal aperture. We also found three plant species that absolutely require BL for both stomatal opening and photosynthetic CO2 fixation, including a gymnosperm, C. revoluta, and the ferns Equisetum hyemale and Psilotum nudum. © 2015 American Society of Plant Biologists. All Rights Reserved.

  2. Quantitative Evaluation of Tumor Early Response to a Vascular-Disrupting Agent with Dynamic PET.

    Science.gov (United States)

    Guo, Ning; Zhang, Fan; Zhang, Xiaomeng; Guo, Jinxia; Lang, Lixin; Kiesewetter, Dale O; Niu, Gang; Li, Quanzheng; Chen, Xiaoyuan

    2015-12-01

    The purpose of this study is to evaluate the early response of tumors to a vascular-disrupting agent (VDA) VEGF121/recombinant toxin gelonin (rGel) using dynamic [(18)F]FPPRGD2 positron emission tomography (PET) and kinetic parameter estimation. Two tumor xenograft models: U87MG (highly vascularized) and A549 (moderately vascularized), were selected, and both were randomized into treatment and control groups. Sixty-minute dynamic PET scans with [(18)F]FPPRGD2 that targets to integrin αvβ3 were performed at days 0 (baseline), 1, and 3 since VEGF121/rGel treatment started. Dynamic PET-derived binding potential (BPND) and parametric maps were compared with tumor uptake (%ID/g) and the static PET image at 1 h after the tracer administration. The growth of U87MG tumor was obviously delayed upon VEGF121/rGel treatment. A549 tumor was not responsive to the same treatment. BPND of treated U87MG tumors decreased significantly at day 1 (p dynamic PET with [(18)F]FPPRGD2 shows advantages in distinguishing effective from ineffective treatment during the course of VEGF121/rGel therapy at early stage and is therefore more sensitive in assessing therapy response than static PET.

  3. Early Transcriptomic Response to LDL and oxLDL in Human Vascular Smooth Muscle Cells.

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    Salvador Damián-Zamacona

    Full Text Available Although nowadays it is well known that the human transcriptome can importantly vary according to external or environmental condition, the reflection of this concept when studying oxidative stress and its direct relationship with gene expression profiling during the process of atherogenesis has not been thoroughly achieved.The ability to analyze genome-wide gene expression through transcriptomics has shown that the genome responds dynamically to diverse stimuli. Here, we describe the transcriptome of human vascular smooth muscle cells (hVSMC stimulated by native and oxidized low-density lipoprotein (nLDL and oxLDL respectively, with the aim of assessing the early molecular changes that induce a response in this cell type resulting in a transcriptomic transformation. This expression has been demonstrated in atherosclerotic plaques in vivo and in vitro, particularly in the light of the oxidative modification hypothesis of atherosclerosis.Total RNA was isolated with TRIzol reagent (Life Technologies and quality estimated using an Agilent 2100 bioanalyzer. The transcriptome of hVSMC under different experimental conditions (1,5 and 24 hours for nLDL and oxLDL was obtained using the GeneChip Human Gene 1.0 ST (Affymetrix designed to measure gene expression of 28,869 well-annotated genes. A fixed fold-change cut-off corresponding to ± 2 was used to identify genes exhibiting the most significant variation and statistical significance (P< 0.05, and 8 genes validated by qPCR using Taqman probes.10 molecular processes were significantly affected in hVSMC: Apoptosis and cell cycle, extracellular matrix remodeling, DNA repair, cholesterol efflux, cGMP biosynthesis, endocytic mechanisms, calcium homeostasis, redox balance, membrane trafficking and finally, the immune response to inflammation. The evidence we present supporting the hypothesis for the involvement of oxidative modification of several processes and metabolic pathways in atherosclerosis is

  4. Molecular Ultrasound Imaging of Early Vascular Response in Prostate Tumors Irradiated with Carbon Ions

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    Moritz Palmowski

    2009-09-01

    Full Text Available Individualized treatments with combination of radiotherapy and targeted drugs require knowledge about the behavior of molecular targets after irradiation. Angiogenic marker expression has been studied after conventional radiotherapy, but little is known about marker response to charged particles. For the very first time, we used molecular ultrasound imaging to intraindividually track changes in angiogenic marker expression after carbon ion irradiation in experimental tumors. Expression of intercellular adhesion molecule-1 (ICAM-1 and of αvβ3-integrin in subcutaneous AT-1 prostate cancers in rats treated with carbon ions (16 Gy was studied using molecular ultrasound and immunohistochemistry. For this purpose, cyanoacrylate microbubbles were synthesized and linked to specific ligands. The accumulation of targeted microbubbles in tumors was quantified before and 36 hours after irradiation. In addition, tumor vascularization was analyzed using volumetric Doppler ultrasound. In tumors, the accumulation of targeted microbubbles was significantly higher than in nonspecific ones and could be inhibited competitively. Before irradiation, no difference in binding of αvβ3-integrin-specific or ICAM-1-specific microbubbles was observed in treated and untreated animals. After irradiation, however, treated animals showed a significantly higher binding of αvβ3-integrin-specific microbubbles and an enhanced binding of ICAM-1-specific microbubbles than untreated controls. In both groups, a decrease in vascularization occurred during tumor growth, but no significant difference was observed between irradiated and nonirradiated tumors. In conclusion, carbon ion irradiation upregulates ICAM-1 and αvβ3-integrin expression in tumor neovasculature. Molecular ultrasound can indicate the regulation of these markers and thus may help to identify the optimal drugs and time points in individualized therapy regimens.

  5. Role of early growth response 1 in arteriogenesis: impact on vascular cell proliferation and leukocyte recruitment in vivo.

    Science.gov (United States)

    Pagel, Judith-Irina; Ziegelhoeffer, Tibor; Heil, Matthias; Fischer, Silvia; Fernández, Borja; Schaper, Wolfgang; Preissner, Klaus T; Deindl, Elisabeth

    2012-03-01

    Based on previous findings that early growth response 1 (Egr-1) participates in leukocyte recruitment and cell proliferation in vitro, this study was designed to investigate its mode of action during arteriogenesis in vivo. In a model of peripheral arteriogenesis, Egr-1 was significantly upregulated in growing collaterals of wild-type (WT) mice, both on mRNA and protein level. Egr-1(-/-) mice demonstrated delayed arteriogenesis after femoral artery ligation. They further showed increased levels of monocytes and granulocytes in the circulation, but reduced levels in adductor muscles under baseline conditions. After femoral artery ligation, elevated numbers of macrophages were detected in the perivascular zone of collaterals in Egr-1(-/-) mice and mRNA of leukocyte recruitment mediators was upregulated. Other Egr family members (Egr-2 to -4) were significantly upregulated only in Egr-1(-/-) mice, suggesting a mechanism of counterbalancing Egr-1 deficiency. Moreover, splicing factor-1, downregulated in WT mice after femoral artery ligation in the process of increased vascular cell proliferation, was upregulated in Egr-1(-/-) mice. αSM-actin on the other hand, significantly downregulated in WT mice, showed no differential expression in Egr-1(-/-) mice. While cell cycle regulator cyclin E and cdc20 were upregulated in Egr-1(-/-) mice, cyclin D1 expression decreased below the detection limit in collaterals, and the proliferation marker ki67 was not differentially expressed. In conclusion, compensation for deficiency in Egr-1 function in leukocyte recruitment can presumably be mediated by other transcription factors; however, Egr-1 is indispensable for effective vascular cell cycle progression in arteriogenesis.

  6. TH-E-BRF-03: A Multivariate Interaction Model for Assessment of Hippocampal Vascular Dose-Response and Early Prediction of Radiation-Induced Neurocognitive Dysfunction

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    Farjam, R; Pramanik, P; Srinivasan, A; Chapman, C; Tsien, C; Lawrence, T; Cao, Y [University of Michigan, Ann Arbor, MI (United States)

    2014-06-15

    Purpose: Vascular injury could be a cause of hippocampal dysfunction leading to late neurocognitive decline in patients receiving brain radiotherapy (RT). Hence, our aim was to develop a multivariate interaction model for characterization of hippocampal vascular dose-response and early prediction of radiation-induced late neurocognitive impairments. Methods: 27 patients (17 males and 10 females, age 31–80 years) were enrolled in an IRB-approved prospective longitudinal study. All patients were diagnosed with a low-grade glioma or benign tumor and treated by 3-D conformal or intensity-modulated RT with a median dose of 54 Gy (50.4–59.4 Gy in 1.8− Gy fractions). Six DCE-MRI scans were performed from pre-RT to 18 months post-RT. DCE data were fitted to the modified Toft model to obtain the transfer constant of gadolinium influx from the intravascular space into the extravascular extracellular space, Ktrans, and the fraction of blood plasma volume, Vp. The hippocampus vascular property alterations after starting RT were characterized by changes in the hippocampal mean values of, μh(Ktrans)τ and μh(Vp)τ. The dose-response, Δμh(Ktrans/Vp)pre->τ, was modeled using a multivariate linear regression considering integrations of doses with age, sex, hippocampal laterality and presence of tumor/edema near a hippocampus. Finally, the early vascular dose-response in hippocampus was correlated with neurocognitive decline 6 and 18 months post-RT. Results: The μh(Ktrans) increased significantly from pre-RT to 1 month post-RT (p<0.0004). The multivariate model showed that the dose effect on Δμh(Ktrans)pre->1M post-RT was interacted with sex (p<0.0007) and age (p<0.00004), with the dose-response more pronounced in older females. Also, the vascular dose-response in the left hippocampus of females was significantly correlated with memory function decline at 6 (r = − 0.95, p<0.0006) and 18 (r = −0.88, p<0.02) months post-RT. Conclusion: The hippocampal vascular

  7. TH-E-BRF-03: A Multivariate Interaction Model for Assessment of Hippocampal Vascular Dose-Response and Early Prediction of Radiation-Induced Neurocognitive Dysfunction

    International Nuclear Information System (INIS)

    Farjam, R; Pramanik, P; Srinivasan, A; Chapman, C; Tsien, C; Lawrence, T; Cao, Y

    2014-01-01

    Purpose: Vascular injury could be a cause of hippocampal dysfunction leading to late neurocognitive decline in patients receiving brain radiotherapy (RT). Hence, our aim was to develop a multivariate interaction model for characterization of hippocampal vascular dose-response and early prediction of radiation-induced late neurocognitive impairments. Methods: 27 patients (17 males and 10 females, age 31–80 years) were enrolled in an IRB-approved prospective longitudinal study. All patients were diagnosed with a low-grade glioma or benign tumor and treated by 3-D conformal or intensity-modulated RT with a median dose of 54 Gy (50.4–59.4 Gy in 1.8− Gy fractions). Six DCE-MRI scans were performed from pre-RT to 18 months post-RT. DCE data were fitted to the modified Toft model to obtain the transfer constant of gadolinium influx from the intravascular space into the extravascular extracellular space, Ktrans, and the fraction of blood plasma volume, Vp. The hippocampus vascular property alterations after starting RT were characterized by changes in the hippocampal mean values of, μh(Ktrans)τ and μh(Vp)τ. The dose-response, Δμh(Ktrans/Vp)pre->τ, was modeled using a multivariate linear regression considering integrations of doses with age, sex, hippocampal laterality and presence of tumor/edema near a hippocampus. Finally, the early vascular dose-response in hippocampus was correlated with neurocognitive decline 6 and 18 months post-RT. Results: The μh(Ktrans) increased significantly from pre-RT to 1 month post-RT (p<0.0004). The multivariate model showed that the dose effect on Δμh(Ktrans)pre->1M post-RT was interacted with sex (p<0.0007) and age (p<0.00004), with the dose-response more pronounced in older females. Also, the vascular dose-response in the left hippocampus of females was significantly correlated with memory function decline at 6 (r = − 0.95, p<0.0006) and 18 (r = −0.88, p<0.02) months post-RT. Conclusion: The hippocampal vascular

  8. Enhancing the radiation response of tumors but not early or late responding normal tissues using a vascular disrupting agent

    DEFF Research Database (Denmark)

    Horsman, Michael R

    2017-01-01

    INTRODUCTION: Vascular disrupting agents (VDAs) damage tumor vasculature and enhance tumor radiation response. In this pre-clinical study, we combined radiation with the leading VDA in clinical development, combretastatin A-4 phosphate (CA4P), and compared the effects seen in tumors and relevant...... normal tissues. MATERIAL AND METHODS: Radiation was applied locally to tissues in CDF1 mice to produce full radiation dose-response curves. CA4P (250 mg/kg) was intraperitoneally (i.p.) injected within 30 minutes after irradiating. Response of 200 mm3 foot implanted C3H mammary carcinomas was assessed......% increase in ventilation rate measured by plethysmography within 9 months). A Chi-squared test was used for statistical comparisons (significance level of p 4P. The radiation...

  9. WE-FG-202-02: Exploration of High-Resolution Quantitative Ultrasonic Micro-Vascular Imaging for Early Assessment of Radiotherapy Tumor Response

    Energy Technology Data Exchange (ETDEWEB)

    Kasoji, S; Rivera, J; Dayton, P [University of North Carolina- Chapel Hill/ North Carolina State University, Chapel Hill, NC (United States); Buse, J [UNC School of Medicine, Chapel Hill, NC (United States); Chang, S [University of North Carolina- Chapel Hill/ North Carolina State University, Chapel Hill, NC (United States); UNC School of Medicine, Chapel Hill, NC (United States)

    2016-06-15

    Purpose: Currently, we cannot predict an individual patient’s response to a given radiotherapy which normally is not detected for weeks to months post-treatment. As a result, precious time is wasted for patients with unresponsive tumors who could have switched to an alternative treatment much earlier. Presently, no early treatment response detection method exists that is effective, low-cost, non-invasive, and safe. We hypothesize that changes in tumor microvasculature predict tumor response to radiotherapy earlier than tumor volume changes. Recent radiobiology research suggests tumors undergo vascular remodeling in response to radiation well before manifesting changes in tumor volume. We propose monitoring tumor microvasculature post-radiation using Acoustic Angiography (AA), a novel ultrasound imaging modality developed and patented in-house. In this study, we investigate whether changes in tumor microvasculature, measured using AA, can be an early indicator of high-dose radiotherapy success, compared to changes in tumor volume. Methods: Fibrosarcoma xenograft tumor tissue was subcutaneously implanted into rodent flanks (N=10). Animal tumors (N=8) were irradiated with a single treatment of 15Gy using a clinical LINAC at 100SSD and 2×2cm field size. Two untreated rats were left as tumor controls. AA imaging was performed immediately posttreatment and every third day thereafter for 30 days, or until tumors disappeared. Tumor volumes and vascular densities were measured from anatomical b-mode ultrasound and AA images, respectively. Results: Statistical differences in vascular density between treatment responders and non-responders were observed on Day 10 (p=0.005), whereas statistical differences in tumor volume were not observed until Day 19 (p=0.02). Conclusions: Tumor vascularity differences may be observed substantially earlier than differences in tumor size. In addition, significant early increases in vascular density were observed in non-responding tumors

  10. DCE-MRI-Derived Parameters in Evaluating Abraxane-Induced Early Vascular Response and the Effectiveness of Its Synergistic Interaction with Cisplatin.

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    Xilin Sun

    Full Text Available Our previous studies revealed molecular alterations of tumor vessels, varying from immature to mature alterations, resulting from Abraxane, and demonstrated that the integrin-specific PET tracer 18F-FPPRGD2 can be used to noninvasively monitor such changes. However, changes in the tumor vasculature at functional levels such as perfusion and permeability are also important for monitoring Abraxane treatment outcomes in patients with cancer. The purpose of this study is to further investigate the vascular response during Abraxane therapy and the effectiveness of its synergistic interaction with cisplatin using Dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI. Thirty MDA-MB-435 tumor mice were randomized into three groups: PBS control (C group, Abraxane only (A group, and sequential treatment with Abraxane followed by cisplatin (A-P group. Tumor volume was monitored based on caliper measurements. A DCE-MRI protocol was performed at baseline and day 3. The Ktrans, Kep and Ve were calculated and compared with CD31, α-SMA, and Ki67 histology data. Sequential treatment with Abraxane followed by cisplatin produced a significantly greater inhibition of tumor growth during the three weeks of the observation period. Decreases in Ktrans and Kep for the A and A-P groups were observed on day 3. Immunohistological staining suggested vascular remodeling during the Abraxane therapy. The changes in Ktrans and Kep values were correlated with alterations in the permeability of the tumor vasculature induced by the Abraxane treatment. In conclusion, Abraxane-mediated permeability variations in tumor vasculature can be quantitatively visualized by DCE-MRI, making this a useful method for studying the effects of early cancer treatment, especially the early vascular response. Vascular remodeling by Abraxane improves the efficiency of cisplatin delivery and thus results in a favorable treatment outcome.

  11. Early vascular plants in the Czech Republic

    OpenAIRE

    Uhlířová, Monika

    2017-01-01

    Vascular plants are characterized as a group of plants, which are already fully adapted to live on the land. Their evolution is a result of a set of adaptations that have required the necessary changes at anatomical and morphological level. Some evidences about the rise of vascular plants appear in the fossil record from the Middle Ordovician in the form of spores and later also from the Early Silurian in the form of megafossils. The aim of the thesis is to briefly describe and discuss the mo...

  12. Vascular Steal Explains Early Paradoxical Blood Oxygen Level-Dependent Cerebrovascular Response in Brain Regions with Delayed Arterial Transit Times

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    Julien Poublanc

    2013-04-01

    Full Text Available Introduction: Blood oxygen level-dependent (BOLD magnetic resonance imaging (MRI during manipulation of inhaled carbon dioxide (CO2 can be used to measure cerebrovascular reactivity (CVR and map regions of exhausted cerebrovascular reserve. These regions exhibit a reduced or negative BOLD response to inhaled CO2. In this study, we sought to clarify the mechanism behind the negative BOLD response by investigating its time delay (TD. Dynamic susceptibility contrast (DSC MRI with the injection of a contrast agent was used as the gold standard in order to provide measurement of the blood arrival time to which CVR TD could be compared. We hypothesize that if negative BOLD responses are the result of a steal phenomenon, they should be synchronized with positive BOLD responses from healthy brain tissue, even though the blood arrival time would be delayed. Methods: On a 3-tesla MRI system, BOLD CVR and DSC images were collected in a group of 19 patients with steno-occlusive cerebrovascular disease. For each patient, we generated a CVR magnitude map by regressing the BOLD signal with the end-tidal partial pressure of CO2 (PETCO2, and a CVR TD map by extracting the time of maximum cross-correlation between the BOLD signal and PETCO2. In addition, a blood arrival time map was generated by fitting the DSC signal with a gamma variate function. ROI masks corresponding to varying degrees of reactivity were constructed. Within these masks, the mean CVR magnitude, CVR TD and DSC blood arrival time were extracted and averaged over the 19 patients. CVR magnitude and CVR TD were then plotted against DSC blood arrival time. Results: The results show that CVR magnitude is highly correlated to DSC blood arrival time. As expected, the most compromised tissues with the longest blood arrival time have the lowest (most negative CVR magnitude. However, CVR TD shows a noncontinuous relationship with DSC blood arrival time. CVR TD is well correlated to DSC blood arrival time

  13. Early Vascular Ageing - A Concept in Development.

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    M Nilsson, Peter

    2015-04-01

    Cardiovascular disease (CVD) is a prevalent condition in the elderly, often associated with metabolic disturbance and type 2 diabetes. For a number of years, research dedicated to understand atherosclerosis dominated, and for many good reasons, this pathophysiological process being proximal to the CVD events. In recent years, research has been devoted to an earlier stage of vascular pathology named arteriosclerosis (arterial stiffness) and the new concept of early vascular ageing (EVA), developed by a group of mostly European researchers. This overview describes recent developments in research dedicated to EVA and new emerging aspects found in studies of families at high cardiovascular risk. There are new aspects related to genetics, telomere biology and the role of gut microbiota. However, there is still no unifying definition available of EVA and no direct treatment, but rather only recommendations for conventional cardiovascular risk factor control. New interventions are being developed - not only new antihypertensive drugs, but also new drugs for vascular protection - the selective angiotensin-II (AT2) agonist Compound 21 (C21). Human studies are eagerly awaited. Even new functional food products could have the potential to positively influence cardiometabolic regulation, to be confirmed.

  14. Recommendations for measurement of tumour vascularity with positron emission tomography in early phase clinical trials

    International Nuclear Information System (INIS)

    Aboagye, Eric O.; Kenny, Laura M.; Myers, Melvyn; Gilbert, Fiona J.; Fleming, Ian N.; Beer, Ambros J.; Cunningham, Vincent J.; Marsden, Paul K.; Visvikis, Dimitris; Gee, Antony D.; Groves, Ashley M.; Cook, Gary J.; Kinahan, Paul E.; Clarke, Larry

    2012-01-01

    The evaluation of drug pharmacodynamics and early tumour response are integral to current clinical trials of novel cancer therapeutics to explain or predict long term clinical benefit or to confirm dose selection. Tumour vascularity assessment by positron emission tomography could be viewed as a generic pharmacodynamic endpoint or tool for monitoring response to treatment. This review discusses methods for semi-quantitative and quantitative assessment of tumour vascularity. The radioligands and radiotracers range from direct physiological functional tracers like [ 15 O]-water to macromolecular probes targeting integrin receptors expressed on neovasculature. Finally we make recommendations on ways to incorporate such measurements of tumour vascularity into early clinical trials of novel therapeutics. (orig.)

  15. Neutrophil Influx and Chemokine Production during the Early Phases of the Antitumor Response to the Vascular Disrupting Agent DMXAA (ASA404

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    Liang-Chuan S. Wang

    2009-08-01

    Full Text Available 5,6-Dimethylxanthenone-4-acetic acid (DMXAA acts through tumor vascular disruption and cytokine production and is the first of its class to enter phase 3 trials. We characterized leukocytes and cytokines in murine Colon 38 tumors before and after DMXAA treatment. Tumor mass declined 50% 24 hours after DMXAA administration, but the leukocyte count per gram of tumor increased threefold owing to a large influx of Ly6G+CD11b+F4/80−. cells with the morphology of neutrophils. However, B and T lymphocytes, natural killer cells, and macrophages in the tumor all decreased in numbers. Seven chemokines were substantially induced in the tumor, spleen, and serum 4 hours after DMXAA administration. Using cultured spleen cell subpopulations, CD11b+ cells (largely monocytes and macrophages were shown to be the primary producers of tumor necrosis factor á, interleukin 6 (IL-6, and macrophage inflammatory 1α (MIP-1α. CD49b+ natural killer cells produced IP-10, whereas CD45R+ B lymphocytes produced regulated upon activation normal T cell express sequence. T lymphocytes were not major producers of cytokines in the response to DMXAA. Murine peripheral blood leukocytes (PBLs produced a similar panel of cytokines in culture to that detected in mouse serum after DMXAA treatment. Cytokines in human PBL cultures were subsequently measured with the aim of identifying potential serum markers of the human response to DMXAA. IP-10 (P < .001, monocyte chemoattractant protein 1 (P < .001, and sCD40L (P < .01 were decreased, whereas IL-8 (P < .001 and MIP-1α (P = .03 were increased in DMXAA-treated compared with untreated PBL cultures from a group of 12 donors.

  16. Ultra-hydrophilic stent platforms promote early vascular healing and minimise late tissue response: a potential alternative to second-generation drug-eluting stents.

    Science.gov (United States)

    Kolandaivelu, Kumaran; Bailey, Lynn; Buzzi, Stefano; Zucker, Arik; Milleret, Vincent; Ziogas, Algirdas; Ehrbar, Martin; Khattab, Ahmed A; Stanley, James R L; Wong, Gee K; Zani, Brett; Markham, Peter M; Tzafriri, Abraham R; Bhatt, Deepak L; Edelman, Elazer R

    2017-04-20

    Simple surface modifications can enhance coronary stent performance. Ultra-hydrophilic surface (UHS) treatment of contemporary bare metal stents (BMS) was assessed in vivo to verify whether such stents can provide long-term efficacy comparable to second-generation drug-eluting stents (DES) while promoting healing comparably to BMS. UHS-treated BMS, untreated BMS and corresponding DES were tested for three commercial platforms. A thirty-day and a 90-day porcine coronary model were used to characterise late tissue response. Three-day porcine coronary and seven-day rabbit iliac models were used for early healing assessment. In porcine coronary arteries, hydrophilic treatment reduced intimal hyperplasia relative to the BMS and corresponding DES platforms (1.5-fold to threefold reduction in 30-day angiographic and histological stenosis; p<0.04). Endothelialisation was similar on UHS-treated BMS and untreated BMS, both in swine and rabbit models, and lower on DES. Elevation in thrombotic indices was infrequent (never observed with UHS, rare with BMS, most often with DES), but, when present, correlated with reduced endothelialisation (p<0.01). Ultra-hydrophilic surface treatment of contemporary stents conferred good healing while moderating neointimal and thrombotic responses. Such surfaces may offer safe alternatives to DES, particularly when rapid healing and short dual antiplatelet therapy (DAPT) are crucial.

  17. Recommendations for measurement of tumour vascularity with positron emission tomography in early phase clinical trials

    Energy Technology Data Exchange (ETDEWEB)

    Aboagye, Eric O.; Kenny, Laura M.; Myers, Melvyn [Imperial College London, Department of Surgery and Cancer, Faculty of Medicine, London (United Kingdom); Gilbert, Fiona J. [University of Cambridge, Radiology Department, Cambridge (United Kingdom); Fleming, Ian N. [University of Aberdeen, NCRI PET Research Network, Aberdeen Bioimaging Centre, Aberdeen (United Kingdom); Beer, Ambros J. [Technische Universitaet Munchen, Klinikum rechts der Isar, Department of Nuclear Medicine, Munich (Germany); Cunningham, Vincent J. [University of Aberdeen, Institute of Medical Sciences, Aberdeen (United Kingdom); Marsden, Paul K. [St. Thomas' Hospital, Division of Imaging Sciences, PET Imaging Centre, London (United Kingdom); Visvikis, Dimitris [INSERM National Institute of Health and Clinical Sciences LaTIM, CHU Morvan, Brest (France); Gee, Antony D. [St. Thomas' Hospital, Division of Imaging Sciences, The Rayne Institute, London (United Kingdom); Groves, Ashley M. [University College London, University College Hospital, Institute of Nuclear Medicine, London (United Kingdom); Cook, Gary J. [St. Thomas' Hospital, KCL Division of Imaging, Sciences and Biomedical Engineering, PET Imaging Centre, London (United Kingdom); Kinahan, Paul E. [University of Washington, 222 Old Fisheries Center (FIS), Box 357987, Seattle, WA (United States); Clarke, Larry [Cancer Imaging Program, Imaging Technology Development Branch, Rockville, MD (United States)

    2012-07-15

    The evaluation of drug pharmacodynamics and early tumour response are integral to current clinical trials of novel cancer therapeutics to explain or predict long term clinical benefit or to confirm dose selection. Tumour vascularity assessment by positron emission tomography could be viewed as a generic pharmacodynamic endpoint or tool for monitoring response to treatment. This review discusses methods for semi-quantitative and quantitative assessment of tumour vascularity. The radioligands and radiotracers range from direct physiological functional tracers like [{sup 15}O]-water to macromolecular probes targeting integrin receptors expressed on neovasculature. Finally we make recommendations on ways to incorporate such measurements of tumour vascularity into early clinical trials of novel therapeutics. (orig.)

  18. Early Detection System of Vascular Disease and Its Application Prospect

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    Huan Liu

    2016-01-01

    Full Text Available Markers of imaging, structure, and function reflecting vascular damage, integrating a long time accumulation effect of traditional and unrecognized cardiovascular risk factors, can be regarded as surrogate endpoints of target organ damage before the occurrence of clinical events. Prevention of cardiovascular disease requires risk stratification and treatment of traditional risk factors, such as smoking, hypertension, hyperlipidemia, and diabetes. However, traditional risk stratification is not sufficient to provide accurate assessment of future cardiovascular events. Therefore, vascular injury related parameters obtained by ultrasound or other noninvasive devices, as a surrogate parameter of subclinical cardiovascular disease, can improve cardiovascular risk assessment and optimize the preventive treatment strategy. Thus, we will summarize the research progress and clinical application of early assessment technology of vascular diseases in the present review.

  19. Early experience of endovascular treatment of peripheral vascular disease

    International Nuclear Information System (INIS)

    Ashraf, T.; Yousuf, K.; Karim, M.T.

    2015-01-01

    Atherosclerotic peripheral arterial disease (PAD) is prevalent affecting up to 16% of the population aged 55 years or older. Endovascular intervention for the treatment of limb ischemia has become the first line therapy but in Pakistan it is in embryonic stage due to dearth of trained persons and dedicated centres. This study was conducted to evaluate procedural success and early outcome of endovascular treatment of peripheral vascular disease. Methods: A prospective single arm multicentre study was conducted at the National Institute of Cardiovascular Disease and National Medical Centre, Karachi, Pakistan from January 2013 to June 2014. A total of 25 patients were enrolled in the study that underwent endovascular treatment. Out of 25 patients 23 (92%) had critical limb ischemia (CLI) as per TASC II classification (A to D) and 2 (8%) had carotid lesion with history of TIA. Patients of acute limb ischemia and stroke were excluded. Ankle brachial index (ABI) was classified as normal (0.9-1.3), mild (0.7-0.9), moderate (0.4-0.69), severe (<0.4). Outcome was taken as immediate success and symptoms, amputation of limb among CLI patients and incidence of stroke in patients with carotid artery lesion at end of six months. Results: Among aortoiliac, femoropopliteal and tibioperoneal lesions, tibioperoneal lesions at six months were found to be more symptomatic 6 (86%) and amputation 4 (57%). Two carotid lesions at follow up were asymptomatic without stroke. Conclusion: Endovascular treatment of peripheral vascular lesions, i.e., aortoiliac, femoropopliteal tibioperoneal and carotid lesions were satisfactory in immediate outcome. Tibioperoneal lesions were more symptomatic and limb amputation at six months. (author)

  20. FLAIR vascular hyperintensities predict early ischemic recurrence in TIA.

    Science.gov (United States)

    Nam, Ki-Woong; Kim, Chi Kyung; Kim, Tae Jung; Oh, Kyungmi; Han, Moon-Ku; Ko, Sang-Bae; Yoon, Byung-Woo

    2018-02-27

    To evaluate the relationship between fluid-attenuated inversion recovery (FLAIR) vascular hyperintensity (FVH) and early ischemic lesion recurrence (follow-up diffusion-weighted imaging [FU-DWI] [+]) in patients with lesion-negative TIA. We recruited consecutive patients with lesion-negative TIA within 24 hours of symptom onset, who underwent follow-up MRI during the acute period. FVH was defined as a focal or serpentine high signal intensity on FLAIR images. Other potential confounders were adjusted to evaluate the relationship between FVH and FU-DWI (+). Furthermore, to compare clinical outcomes between the FU-DWI (+) and FU-DWI (-) groups, we assessed 1-year recurrent ischemic stroke or TIA. Among 392 patients with lesion-negative TIA, 82 patients had FU-DWI (+) on the follow-up MRI. In the multivariate analysis, FVH remained an independent predictor of FU-DWI (+) (adjusted odds ratio [aOR] = 4.77, 95% confidence interval [CI] 2.45-9.29, p TIA. As FU-DWI (+) frequently occurs during the acute period and has a subsequent worse outcome after discharge, additional radiologic or clinical markers for it are necessary. © 2018 American Academy of Neurology.

  1. Serial assessment by optical coherence tomography of early and late vascular responses after implantation of an absorbable-coating Sirolimus-Eluting stent (from the first-in-human DESSOLVE I trial).

    Science.gov (United States)

    Attizzani, Guilherme F; Bezerra, Hiram G; Ormiston, John; Wang, Wei; Donohoe, Dennis; Wijns, William; Costa, Marco A

    2013-11-15

    The initial enthusiasm caused by the potent antirestenotic effect of early generation drug-eluting stents was recently plagued by concerns regarding their safety profile. Investigators worldwide were stimulated, therefore, to seek for improvement in drug-eluting stent technology, such as eliminating their permanent polymer blamed for vascular inflammation and delayed healing. Optical coherence tomography (OCT) assessments of stent-vessel interactions are used as a surrogate for vessel healing after DES implantation. Herewith, we report serial OCT assessments of vascular reactions to the implantation of a novel absorbable polymer sirolimus-eluting stent (MiStent). In total, 30 patients were included. At 4-, 6-, and 8-month follow-up, different groups of 10 patients underwent OCT imaging, whereas all the patients had OCT assessments scheduled at 18-month follow-up. A total of 13,569 stent struts were analyzed. Low rates of uncovered (14.34 ± 15.35%, 6.62 ± 10.93%, 3.51 ± 2.87%, and 0.84 ± 1.15%, respectively, p stent struts coupled with thin and increasingly homogenous neointimal proliferation were demonstrated. Neointimal area increased from 4- to 8-month follow-up (0.46 ± 0.29 and 1.12 ± 0.73 mm(2), respectively, p stent struts (8.8%, 3.1%, 0.3%, and 0%, respectively, p absorbable polymer sirolimus-eluting stent-vessel interactions up to 18-month follow-up. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Vascular Hyperpermeability Response in Animals Systemically Exposed to Arsenic.

    Science.gov (United States)

    Chen, Shih-Chieh; Chang, Chao-Yuah; Lin, Ming-Lu

    2018-01-01

    The mechanisms underlying cardiovascular diseases induced by chronic exposure to arsenic remain unclarified. The objectives of this study were to investigate whether increased vascular leakage is induced by inflammatory mustard oil in mice systemically exposed to various doses of arsenic and whether an increased vascular leakage response is still present in arsenic-fed mice after arsenic discontinuation for 2 or 6 months. ICR mice were fed water or various doses of sodium arsenite (10, 15, or 20 mg/kg/day; 5 days/week) for 8 weeks. In separate experiments, the mice were treated with sodium arsenite (20 mg/kg) for 2 or 8 weeks, followed by arsenic discontinuation for 2 or 6 months. Vascular permeability to inflammatory mustard oil was quantified using Evans blue (EB) techniques. Both arsenic-exposed and water-fed (control) mice displayed similar basal levels of EB leakage in the ears brushed with mineral oil, a vehicle of mustard oil. The levels of EB leakage induced by mustard oil in the arsenic groups fed with sodium arsenite (10 or 15 mg/kg) were similar to those of water-fed mice. However, increased levels of EB leakage in response to mustard oil stimulation were significantly higher in mice treated with sodium arsenite (20 mg/kg; high dose) than in arsenic-fed (10 or 15 mg/kg; low and middle doses) or control mice. After arsenic discontinuation for 2 or 6 months, mustard oil-induced vascular EB leakage in arsenic-fed (20 mg/kg) mice was similar to that in control mice. Dramatic increases in mustard oil-induced vascular leakage were only present in mice systemically exposed to the high arsenic dose, indicating the synergistic effects of the high arsenic dose and mustard oil.

  3. Eccentric-exercise induced inflammation attenuates the vascular responses to mental stress

    NARCIS (Netherlands)

    Paine, N.J.; Ring, C.; Aldred, S.; Bosch, J.A.; Wadley, A.J.; Veldhuijzen van Zanten, J.J.C.S.

    2013-01-01

    Mental stress has been identified as a trigger of myocardial infarction (MI), with inflammation and vascular responses to mental stress independently implicated as contributing factors. This study examined whether inflammation moderates the vascular responses to mental stress. Eighteen healthy male

  4. Vascular Response of the Segments Adjacent to the Proximal and Distal Edges of the ABSORB Everolimus-Eluting Bioresorbable Vascular Scaffold

    DEFF Research Database (Denmark)

    Gogas, Bill D; Serruys, Patrick W; Diletti, Roberto

    2012-01-01

    This study sought to investigate in vivo the vascular response at the proximal and distal edges of the second-generation ABSORB everolimus-eluting bioresorbable vascular scaffold (BVS).......This study sought to investigate in vivo the vascular response at the proximal and distal edges of the second-generation ABSORB everolimus-eluting bioresorbable vascular scaffold (BVS)....

  5. Vaccine-induced inflammation attenuates the vascular responses to mental stress

    NARCIS (Netherlands)

    Paine, N.J.; Ring, C.; Bosch, J.A.; Drayson, M.T.; Aldred, S.; Veldhuijzen van Zanten, J.J.C.S.

    2014-01-01

    Inflammation is associated with poorer vascular function, with evidence to suggest that inflammation can also impair the vascular responses to mental stress. This study examined the effects of vaccine-induced inflammation on vascular responses to mental stress in healthy participants. Eighteen male

  6. Endurance exercise training increases peripheral vascular response in human fingers.

    Science.gov (United States)

    Katayama, K; Shimoda, M; Maeda, J; Takemiya, T

    1998-10-01

    The purpose of this study was to clarify whether peripheral vascular response to alteration of transmural pressure is changed by endurance exercise training. The healthy male subjects (training group; n = 6) performed endurance exercise training that consisted of cycle ergometer exercise 5 d.week-1 and 30 min.d-1 for a period of 8 weeks. Changes in the peripheral vascular response to alteration of transmural pressure in the human finger were measured by a differential digital photoplethysmogram (DeltaDPG) and blood pressure during passive movement of the arm to different vertical hand positions relative to heart level. Following 8 weeks of endurance training, percent changes in DeltaDPG from heart level in the training group increased significantly (mean +/- SD, -48.1 +/- 7. 3 to -58.7 +/- 9.3% at the lowered position, 46.1 +/- 13.4 to 84.6 +/- 8.8% at the elevated position, ppressure, also significantly changed in the training group over the 8 weeks (5.6 +/- 1.3 to 2.7 +/- 1.6 mV. V-1.s-1.mmHg-1 at the lowered position, 30.0 +/- 12.4 to 54.4 +/- 18. 9 mV.V-1.s-1.mmHg-1 at the elevated position ). Maximal oxygen uptake (V.O2 max) was significantly increased in the training group. On the other hand, the control group (n = 6) showed no significant changes in all parameters for 8 weeks. Therefore these results suggest that endurance exercise training induces an increase in peripheral vascular response to alteration of transmural pressure in the human finger.

  7. The relationship between copper, homocysteine and early vascular disease in lean women with polycystic ovary syndrome.

    Science.gov (United States)

    Celik, Cem; Bastu, Ercan; Abali, Remzi; Alpsoy, Seref; Guzel, Eda Celik; Aydemir, Birsen; Yeh, John

    2013-05-01

    This study investigates copper (Cu) levels and vascular dysfunction in lean women with polycystic ovary syndrome (PCOS). 44 subjects with PCOS, diagnosed according to Rotterdam criteria, and 42 healthy subjects matched for body mass index and age. Comparison of serum Cu, homocysteine, carotid intima-media thickness (CIMT), brachial artery flow mediated dilation (FMD) was carried out between PCOS patients and the control group. Clinical study was done in Namik Kemal University School of Medicine. The CIMT and concentration of Cu in PCOS patients was significantly higher than the healthy controls. FMD levels in PCOS patients were significantly lower than those in controls. In PCOS patients, CIMT was correlated with estrogen and Cu levels. However, FMD was correlated with age and Cu levels. Among these contributing factors, Cu levels were correlated with a change in CIMT and FMD. CIMT and FMD in PCOS patients were related to Cu levels as well as several cardiovascular risk factors. Thus, increased Cu levels may be responsible for the increased risk of early vascular disease in women with PCOS.

  8. Short-term vascular hemodynamic responses to isometric exercise in young adults and in the elderly

    NARCIS (Netherlands)

    Hartog, R. (Renee); D. Bolignano (Davide); E.J.G. Sijbrands (Eric); Pucci, G. (Giacomo); F.U.S. Mattace Raso (Francesco)

    2018-01-01

    textabstractBackground: Vascular aging is known to induce progressive stiffening of the large elastic arteries, altering vascular hemodynamics under both rest and stress conditions. In this study, we aimed to investigate changes in vascular hemodynamics in response to isometric handgrip exercise

  9. Vascular adrenergic receptor responses in skeletal muscle in myotonic dystrophy

    International Nuclear Information System (INIS)

    Mechler, F.; Mastaglia, F.L.

    1981-01-01

    The pharmacological responses of vascular adrenergic receptors to intravenously administered epinephrine, phentolamine, and propranolol were assessed by measuring muscle blood flow (MBF) changes in the tibialis anterior muscle using the xenon 133 clearance technique and were compared in 8 normal subjects and 11 patients with myotonic dystrophy. In cases with advanced involvement of the muscle, the resting MBF was reduced and was not significantly altered by epinephrine before or after alpha- or beta-receptor blockade. In patients in whom the tibialis anterior muscle was normal or only minimally affected clinically, a paradoxical reduction in the epinephrine-induced increase in MBF was found after alpha blockade by phentolamine, and the epinephrine-induced MBF increase was not completely blocked by propranolol as in the normal subjects. These findings point to functional alteration in the properties of vascular adrenergic receptors in muscle in myotonic dystrophy. While this may be another manifestation of a widespread cell membrane defect in the disease, the possibility that the changes are secondary to the myotonic state cannot be excluded

  10. The surrounding tissue modifies the placental stem villous vascular responses

    DEFF Research Database (Denmark)

    Brøgger, Torbjørn; Forman, Axel; Aalkjær, Christian

    2014-01-01

    is available. In-depth understanding of the mechanisms involved in control of placental vascular tone are needed to develop new tissue targets for therapeutic intervention. Method: From fresh born placentas segments of stem villous arteries were carefully dissected. The artery branches were divided....... The surrounding trophoblast was removed from one end and left intact in the other, and the segment was divided to give two ring preparations, with or without trophoblast. The preparations were mounted in wire myographs and responses to vasoactive agents were compared. Results: pD2values for PGF2α, Tx-analog U...... or endotheline-1. These differences partly disappeared in the presence of L-NAME. Conclusion: The perivascular tissue significantly reduces sensitivity and force development of stem villous arteries, partly due to release of NO This represents a new mechanism for control of human stem villous artery tone....

  11. Vascular smooth muscle cell apoptosis is an early trigger for hypothyroid atherosclerosis.

    Science.gov (United States)

    Wang, Pei; Xu, Tian-Ying; Guan, Yun-Feng; Zhao, Yan; Li, Zhi-Yong; Lan, Xiao-Hong; Wang, Xia; Yang, Peng-Yuan; Kang, Zhi-Min; Vanhoutte, Paul M; Miao, Chao-Yu

    2014-06-01

    Endothelial dysfunction is an initial and vascular smooth muscle cell (VSMC) apoptosis, a later step of atherosclerosis. Hypothyroidism accelerates atherosclerosis. However, the early events responsible for this pro-atherosclerotic effect are unclear. Rats were resistant to induction of atherosclerosis by high cholesterol diet alone, but became susceptible in hypothyroid state achieved by administration of propylthiouracil (PTU) for 6 weeks. VSMC dysfunction and apoptosis were obvious within 1 week after PTU treatment, without signs of endothelial dysfunction. This early VSMC damage was caused by hypothyroidism but not the high cholesterol diet. In ApoE knockout mice, PTU-induced hypothyroidism triggered early VSMC apoptosis, increased oxidative stress, and accelerated atherosclerosis development. Thyroid hormone supplementation (T4, 10, or 50 μg/kg) prevented atherogenic phenotypes in hypothyroid rats and mice. In rats, thyroidectomy caused severe hypothyroidism 5 days after operation, which also led to rapid VSMC dysfunction and apoptosis. In vitro studies did not show a direct toxic effect of PTU on VSMCs. In contrast, thyroid hormone (T3, 0.75 μg/L plus T4, 50 nmol/L) exerted a direct protection against VSMC apoptosis, which was reduced by knockdown of TRα1, rather than TRβ1 and TRβ2 receptors. TRα1-mediated inhibition of apoptotic signalling of JNKs and caspase-3 contributed to the anti-apoptotic action of thyroid hormone. These findings provide an in vivo example for VSMC apoptosis as an early trigger of hypothyroidism-associated atherosclerosis, and reveal activation of TRα1 receptors to prevent VSMC apoptosis as a therapeutic strategy in this disease. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

  12. Mismatch negativity as a potential neurobiological marker of early-stage Alzheimer disease and vascular dementia.

    Science.gov (United States)

    Jiang, Shixiang; Yan, Chang; Qiao, Zhengxue; Yao, Haiqian; Jiang, Shiquan; Qiu, Xiaohui; Yang, Xiuxian; Fang, Deyu; Yang, Yanjie; Zhang, Limei; Wang, Lina; Zhang, Liming

    2017-04-24

    Alzheimer's disease (AD) and vascular dementia (VD) are serious, irreversible forms of cognitive impairment, which means that an early diagnosis is essential to slow down their progression. One potential neurophysiological biomarker of these diseases is the mismatch negativity (MMN) event-related potentials (ERP) component, which reflects an automatic detection mechanism at the pre-attentive stages of information processing. We evaluated the auditory MMN response in individuals from two patient groups: those in the prodromal stages of AD (P-AD) and those in the prodromal stages of VD (P-VD). Thirty patients (15 P-AD patients and 15 P-VD patients) and 30 age-matched controls were recruited to undergo electrophysiological recordings during the presentation of an auditory deviant-standard-reverse oddball paradigm that was used to elicit genuine MMN responses. We show that over the frontal-central area, the mean amplitude of the MMN was significantly reduced in both the P-AD (p=0.017) and P-VD groups (p=0.013) compared with controls. The MMN peak latency in P-VD patients was significantly shorter than in controls (p=0.027). No MMN response differences between the P-AD and P-VD were found in either the frontal-central or the temporal areas. These results indicate that P-AD and P-VD patients exhibit impaired pre-attentive information processing mechanisms as revealed by the frontal-central area MMN response, which is associated with sensory memory and cognitive deficits. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Vascular Cognitive Impairment Linked to Brain Endothelium Inflammation in Early Stages of Heart Failure in Mice.

    Science.gov (United States)

    Adamski, Mateusz G; Sternak, Magdalena; Mohaissen, Tasnim; Kaczor, Dawid; Wierońska, Joanna M; Malinowska, Monika; Czaban, Iwona; Byk, Katarzyna; Lyngsø, Kristina S; Przyborowski, Kamil; Hansen, Pernille B L; Wilczyński, Grzegorz; Chlopicki, Stefan

    2018-03-26

    Although advanced heart failure (HF) is a clinically documented risk factor for vascular cognitive impairment, the occurrence and pathomechanisms of vascular cognitive impairment in early stages of HF are equivocal. Here, we characterize vascular cognitive impairment in the early stages of HF development and assess whether cerebral hypoperfusion or prothrombotic conditions are involved. Tgαq*44 mice with slowly developing isolated HF triggered by cardiomyocyte-specific overexpression of G-αq*44 protein were studied before the end-stage HF, at the ages of 3, 6, and 10 months: before left ventricle dysfunction; at the stage of early left ventricle diastolic dysfunction (with preserved ejection fraction); and left ventricle diastolic/systolic dysfunction, respectively. In 6- to 10-month-old but not in 3-month-old Tgαq*44 mice, behavioral and cognitive impairment was identified with compromised blood-brain barrier permeability, most significantly in brain cortex, that was associated with myelin sheet loss and changes in astrocytes and microglia. Brain endothelial cells displayed increased E-selectin immunoreactivity, which was accompanied by increased amyloid-β 1-42 accumulation in piriform cortex and increased cortical oxidative stress (8-OHdG immunoreactivity). Resting cerebral blood flow measured by magnetic resonance imaging in vivo was preserved, but ex vivo NO-dependent cortical arteriole flow regulation was impaired. Platelet hyperreactivity was present in 3- to 10-month-old Tgαq*44 mice, but it was not associated with increased platelet-dependent thrombogenicity. We report for the first time that vascular cognitive impairment is already present in the early stage of HF development, even before left ventricle systolic dysfunction. The underlying pathomechanism, independent of brain hypoperfusion, involves preceding platelet hyperreactivity and brain endothelium inflammatory activation. © 2018 The Authors. Published on behalf of the American Heart

  14. Early decision-analytic modeling - a case study on vascular closure devices.

    Science.gov (United States)

    Brandes, Alina; Sinner, Moritz F; Kääb, Stefan; Rogowski, Wolf H

    2015-10-27

    As economic considerations become more important in healthcare reimbursement, decisions about the further development of medical innovations need to take into account not only medical need and potential clinical effectiveness, but also cost-effectiveness. Already early in the innovation process economic evaluations can support decisions on development in specific indications or patient groups by anticipating future reimbursement and implementation decisions. One potential concept for early assessment is value-based pricing. The objective is to assess the feasibility of value-based pricing and product design for a hypothetical vascular closure device in the pre-clinical stage which aims at decreasing bleeding events. A deterministic decision-analytic model was developed to estimate the cost-effectiveness of established vascular closure devices from the perspective of the Statutory Health Insurance system. To identify early benchmarks for pricing and product design, three strategies of determining the product's value are explored: 1) savings from complications avoided by the new device; 2) valuation of the avoided complications based on an assumed willingness-to-pay-threshold (the efficiency frontier approach); 3) value associated with modifying the care pathways within which the device would be applied. Use of established vascular closure devices is dominated by manual compression. The hypothetical vascular closure device reduces overall complication rates at higher costs than manual compression. Maximum cost savings of only about €4 per catheterization could be realized by applying the hypothetical device. Extrapolation of an efficiency frontier is only possible for one subgroup where vascular closure devices are not a dominated strategy. Modifying care in terms of same-day discharge of patients treated with vascular closure devices could result in cost savings of €400-600 per catheterization. It was partially feasible to calculate value-based prices for the

  15. Early vascular ageing in translation: from laboratory investigations to clinical applications in cardiovascular prevention.

    Science.gov (United States)

    Nilsson, Peter M; Boutouyrie, Pierre; Cunha, Pedro; Kotsis, Vasilios; Narkiewicz, Krzysztof; Parati, Gianfranco; Rietzschel, Ernst; Scuteri, Angelo; Laurent, Stephane

    2013-08-01

    The ageing of the vascular tree is a fundamental reflection of biological ageing in general and a determinant of organ function. In the arterial wall this is characterized by a reduction in the elastin content, as well as by an increased content of collagen and its cross-linkages, leading to increased arterial stiffness and elevated central as well as brachial blood pressure, accompanied by increased SBP variability. In recent years a better understanding of these processes have led to the proposal of a condition named early vascular ageing (EVA) in patients with increased arterial stiffness for their age and sex. This is a condition that could increase cardiovascular risk and is associated with various degrees of cognitive dysfunction, as well as other features of biological ageing. This brief review aims to give an update on EVA and how the concept can be used in clinical practice.

  16. Decreased endometrial vascularity and receptivity in unexplained recurrent miscarriage patients during midluteal and early pregnancy phases.

    Science.gov (United States)

    Tan, Shu-Yin; Hang, Fu; Purvarshi, Gowreesunkur; Li, Min-Qing; Meng, Da-Hua; Huang, Ling-Ling

    2015-10-01

    To evaluate the predictive value of three-dimensional (3D)-power Doppler sonography on recurrent miscarriage. The study patients were divided into a recurrent miscarriage group (30 cases) and a normal pregnancy group (21 cases). Measurement of endometrial thickness was performed using two-dimensional transvaginal ultrasound in the midluteal phase. The endometrial volume, vascularization index (VI), flow index (FI), and vascularization-flow index (VFI) in midluteal and placenta volume, as well as the VI, FI, and VFI of early pregnancy were measured using Virtual Organ Computer-aided Analysis of 3D-power Doppler ultrasound. Endometrial thickness, endometrial volume, endometrial vascular data, VI, FI, and VFI of the midluteal phase were lower in the recurrent miscarriage group compared with the normal pregnancy group (p FI between the recurrent miscarriage and control groups during early pregnancy (p > 0.05). The predictive accuracy of endometrial thickness, endometrial volume, VI, FI, and VFI in the midluteal phase, and placenta volume, VI, FI, and VFI in early pregnancy as measured by the receiver operating characteristic curve to predict miscarriage before 12 gestational weeks in participants was 0.681, 0.876, 0.770, 0.720, 0.879, 0.771, 0.907, 0.592, respectively. The 3D-power Doppler ultrasound is a more comprehensive and sensitive method for evaluating endometrial receptivity. Endometrial volume, VI, FI, and VFI in the midluteal phase, as well as VI in early pregnancy, can be considered as predictive factors for recurrent miscarriage. Copyright © 2015. Published by Elsevier B.V.

  17. Aortic VCAM-1: an early marker of vascular inflammation in collagen-induced arthritis.

    Science.gov (United States)

    Denys, Anne; Clavel, Gaëlle; Lemeiter, Delphine; Schischmanoff, Olivier; Boissier, Marie-Christophe; Semerano, Luca

    2016-05-01

    Cardiovascular disease (CVD) is a major cause of morbidity and mortality in rheumatoid arthritis (RA). There are limited experimental data on vascular involvement in arthritis models. To study the link between CVD and inflammation in RA, we developed a model of vascular dysfunction and articular inflammation by collagen-induced arthritis (CIA) in C57Bl/6 (B6) mice. We studied the expression of vascular inflammatory markers in CIA with and without concomitant hyperlipidic diet (HD). Collagen-induced arthritis was induced with intradermal injection of chicken type-II collagen followed by a boost 21 days later. Mice with and without CIA were fed a standard diet or an HD for 12 weeks starting from the day of the boost. Arthritis severity was evaluated with a validated clinical score. Aortic mRNA levels of vascular cell adhesion molecule-1 (VCAM-1), inducible nitric oxide synthase (iNOS) and interleukin-17 were analysed by quantitative RT-PCR. Vascular cell adhesion molecule-1 localization in the aortic sinus was determined by immunohistochemistry. Atherosclerotic plaque presence was assessed in aortas. Collagen-induced arthritis was associated with increased expression of VCAM-1, independent of diet. VCAM-1 overexpression was detectable as early as 4 weeks after collagen immunization and persisted after 15 weeks. The HD induced atheroma plaque formation and aortic iNOS expression regardless of CIA. Concomitant CIA and HD had no additive effect on atheroma or VCAM-1 or iNOS expression. CIA and an HD diet induced a distinct and independent expression of large-vessel inflammation markers in B6 mice. This model may be relevant for the study of CVD in RA. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  18. Early harvesting of the vascularized pedicled nasoseptal flap during endoscopic skull base surgery.

    Science.gov (United States)

    Eloy, Jean Anderson; Patel, Amit A; Shukla, Pratik A; Choudhry, Osamah J; Liu, James K

    2013-01-01

    The vascularized pedicled nasoseptal flap (PNSF) represents a successful option for reconstruction of large skull base defects after expanded endoscopic endonasal approaches (EEA). This vascularized flap can be harvested early or late in the operation depending on the anticipation of high-flow CSF leaks. Each harvesting technique (early vs. late) is associated with different advantages and disadvantages. In this study, we evaluate our experience with early harvesting of the PNSF for repair of large skull base defects after EEA. A retrospective review was performed at a tertiary care medical center on patients who underwent early PNSF harvesting during reconstruction of intraoperative high-flow CSF leaks after EEA between December 2008 and March 2012. Demographic data, repair materials, surgical approach, and incidence of PNSF usage were collected. Eighty-seven patients meeting the inclusion criteria were identified. In 86 procedures (98.9%), the PNSF harvested at the beginning of the operation was used. In 1 case (1.1%), the PNSF was not used because a high-flow intraoperative CSF leak was not encountered. This patient had recurrence of intradural disease 8months later, and the previously elevated PNSF was subsequent used after tumor resection. Based on our data, a high-flow CSF leak and need for a PNSF can be accurately anticipated in patients undergoing EEA for skull base lesions. Because of the advantages of early harvesting of the PNSF and the high preoperative predictive value of CSF leak anticipations, this technique represents a feasible harvesting practice for EEA surgeries. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. The impact of lymph vascular space invasion on recurrence and survival in patients with early stage endometrial cancer.

    Science.gov (United States)

    Loizzi, V; Cormio, G; Lorusso, M; Latorre, D; Falagario, M; Demitri, P; Scardigno, D; Selvaggi, L E

    2014-05-01

    The aim of this study was to determine impact of lymph vascular space involvement (LVSI) on recurrence and survival in early stage of endometrial cancer. From 1991 through 2010, all endometrial cancer patients at University Hospital of Bari, Italy were identified. The Log-rank test and Kaplan-Meyer methods were used for time-to-event analysis to evaluate the effects of on lymph vascular space involvement recurrence rate and survival time. Of the 560 endometrial cancer patients, 525 underwent primary surgery. Of those, 399 had early stage disease. Three hundred and forty women were not found to have LVSI, whereas 59 were found to have lymph vascular space involvement. Forty-nine (12%) patients developed a recurrence and 20 of them showed lymph vascular space involvement. The statistical analysis demonstrated that LVSI was strongly associated with a poor survival (P < 0.0001). Lymph vascular space involvement is associated with a high risk of recurrence and poor overall survival in early stage of endometrial cancer; therefore, the clinical decision to decide whether or not a patient with early stage endometrial cancer should receive adjuvant therapy should be included the evaluation of lymph vascular space involvement. © 2013 John Wiley & Sons Ltd.

  20. Microvascular dysfunction with increased vascular leakage response in mice systemically exposed to arsenic.

    Science.gov (United States)

    Chen, Shih-Chieh; Huang, Shin-Yin; Lu, Chi-Yu; Hsu, Ya-Hung; Wang, Dean-Chuan

    2014-09-01

    The mechanisms underlying cardiovascular disease induced by arsenic exposure are not completely understood. The objectives of this study were to investigate whether arsenic-fed mice have an increased vascular leakage response to vasoactive agents and whether enhanced type-2 protein phosphatase (PP2A) activity is involved in mustard oil-induced leakage. ICR mice were fed water or sodium arsenite (20 mg/kg) for 4 or 8 weeks. The leakage response to vasoactive agents was quantified using the Evans blue (EB) technique or vascular labeling with carbon particles. Increased EB leakage and high density of carbon-labeled microvessels were detected in arsenic-fed mice treated with mustard oil. Histamine induced significantly higher vascular leakage in arsenic-fed mice than in water-fed mice. Pretreatment with the PP2A inhibitor okadaic acid or the neurokinin 1 receptor (NK1R) blocker RP67580 significantly reduced mustard oil-induced vascular leakage in arsenic-fed mice. The protein levels of PP2Ac and NK1R were similar in both groups. PP2A activity was significantly higher in the arsenic-fed mice compared with the control group. These findings indicate that microvessels generally respond to vasoactive agents, and that the increased PP2A activity is involved in mustard oil-induced vascular leakage in arsenic-fed mice. Arsenic may initiate endothelial dysfunction, resulting in vascular leakage in response to vasoactive agents.

  1. Functional imaging to monitor vascular and metabolic response in canine head and neck tumors during fractionated radiotherapy.

    Science.gov (United States)

    Rødal, Jan; Rusten, Espen; Søvik, Åste; Skogmo, Hege Kippenes; Malinen, Eirik

    2013-10-01

    Radiotherapy causes alterations in tumor biology, and non-invasive early assessment of such alterations may become useful for identifying treatment resistant disease. The purpose of the current work is to assess changes in vascular and metabolic features derived from functional imaging of canine head and neck tumors during fractionated radiotherapy. Material and methods. Three dogs with spontaneous head and neck tumors received intensity-modulated radiotherapy (IMRT). Contrast-enhanced cone beam computed tomography (CE-CBCT) at the treatment unit was performed at five treatment fractions. Dynamic (18)FDG-PET (D-PET) was performed prior to the start of radiotherapy, at mid-treatment and at 3-12 weeks after the completion of treatment. Tumor contrast enhancement in the CE-CBCT images was used as a surrogate for tumor vasculature. Vascular and metabolic tumor parameters were further obtained from the D-PET images. Changes in these tumor parameters were assessed, with emphasis on intra-tumoral distributions. Results. For all three patients, metabolic imaging parameters obtained from D-PET decreased from the pre- to the inter-therapy session. Correspondingly, for two of three patients, vascular imaging parameters obtained from both CE-CBCT and D-PET increased. Only one of the tumors showed a clear metabolic response after therapy. No systematic changes in the intra-tumor heterogeneity in the imaging parameters were found. Conclusion. Changes in vascular and metabolic parameters could be detected by the current functional imaging methods. Vascular tumor features from CE-CBCT and D-PET corresponded well. CE-CBCT is a potential method for easy response assessment when the patient is at the treatment unit.

  2. Possible relationships between the early inflammatory response and subsequent fibrosis in rat skin after irradiation

    International Nuclear Information System (INIS)

    Ullrich, R.L.

    1975-01-01

    The possible mechanistic relationships between the early inflammatory response and subsequent fibrosis seen after radiation exposure was studied in rats were given single x ray doses of either 2000 or 5000 rads to standardized fields of the inner thigh. The results suggest that two mechanisms are responsible for the radiation-induced increase in extravasation rate and vascular injury seen early after irradiation. First, direct cytocidal damage of the endothelium; and second, chemically mediated, possibly complement dependent mechanisms. Indirect histological evidence suggests a correlation between the PMN infiltrate and the indirect vascular damage. In addition, one may conclude from these data that both direct and indirect damage to the vasculature play a role in influencing the subsequent late radiation-induced fibrosis; and a decrease in the indirect damage may allow the maintenance of a supportive vasculature at lower doses or allow the reestablishment of a vascular bed in the case of higher doses. (U.S.)

  3. Retinoid-induced expression and activity of an immediate early tumor suppressor gene in vascular smooth muscle cells.

    Directory of Open Access Journals (Sweden)

    Jeffrey W Streb

    2011-04-01

    Full Text Available Retinoids are used clinically to treat a number of hyper-proliferative disorders and have been shown in experimental animals to attenuate vascular occlusive diseases, presumably through nuclear receptors bound to retinoic acid response elements (RARE located in target genes. Here, we show that natural or synthetic retinoids rapidly induce mRNA and protein expression of a specific isoform of A-Kinase Anchoring Protein 12 (AKAP12β in cultured smooth muscle cells (SMC as well as the intact vessel wall. Expression kinetics and actinomycin D studies indicate Akap12β is a retinoid-induced, immediate-early gene. Akap12β promoter analyses reveal a conserved RARE mildly induced with atRA in a region that exhibits hyper-acetylation. Immunofluorescence microscopy and protein kinase A (PKA regulatory subunit overlay assays in SMC suggest a physical association between AKAP12β and PKA following retinoid treatment. Consistent with its designation as a tumor suppressor, inducible expression of AKAP12β attenuates SMC growth in vitro. Further, immunohistochemistry studies establish marked decreases in AKAP12 expression in experimentally-injured vessels of mice as well as atheromatous lesions in humans. Collectively, these results demonstrate a novel role for retinoids in the induction of an AKAP tumor suppressor that blocks vascular SMC growth thus providing new molecular insight into how retiniods may exert their anti-proliferative effects in the injured vessel wall.

  4. An Analysis of Responses to Defibrotide in the Pulmonary Vascular Bed of the Cat.

    Science.gov (United States)

    Kaye, Alan D; Skonieczny, Brendan D; Kaye, Aaron J; Harris, Zoey I; Luk, Eric J

    2016-01-01

    Defibrotide is a polydisperse mixture of single-stranded oligonucleotides with many pharmacologic properties and multiple actions on the vascular endothelium. Responses to defibrotide and other vasodepressor agents were evaluated in the pulmonary vascular bed of the cat under conditions of controlled pulmonary blood flow and constant left atrial pressure. Lobar arterial pressure was increased to a high steady level with the thromboxane A2 analog U-46619. Under increased-tone conditions, defibrotide caused dose-dependent decreases in lobar arterial pressure without altering systemic arterial and left atrial pressures. Responses to defibrotide were significantly attenuated after the administration of the cyclooxygenase inhibitor sodium meclofenamate. Responses to defibrotide were also significantly attenuated after the administration of both the adenosine 1 and 2 receptor antagonists 8-cyclopentyl-1,3-dimethylxanthine and 8-(3-chlorostyryl)caffeine. Responses to defibrotide were not altered after the administration of the vascular selective adenosine triphosphate-sensitive potassium channel blocker U-37883A, or after the administration of the nitric oxide synthase inhibitor L-N-(1-iminoethyl)-ornithine. These data show that defibrotide has significant vasodepressor activity in the pulmonary vascular bed of the cat. They also suggest that pulmonary vasodilator responses to defibrotide are partially dependent on both the activation of the cyclooxygenase enzyme and adenosine 1 and 2 receptor pathways and independent of the activation of adenosine triphosphate-sensitive potassium channels or the synthesis of nitric oxide in the pulmonary vascular bed of the cat.

  5. A continuum of executive function deficits in early subcortical vascular cognitive impairment: A systematic review and meta-analysis.

    Science.gov (United States)

    Sudo, Felipe Kenji; Amado, Patricia; Alves, Gilberto Sousa; Laks, Jerson; Engelhardt, Eliasz

    2017-01-01

    Subcortical Vascular Cognitive Impairment (SVCI) is a clinical continuum of vascular-related cognitive impairment, including Vascular Mild Cognitive Impairment (VaMCI) and Vascular Dementia. Deficits in Executive Function (EF) are hallmarks of the disorder, but the best methods to assess this function have yet to be determined. The insidious and almost predictable course of SVCI and the multidimensional concept of EF suggest that a temporal dissociation of impairments in EF domains exists early in the disorder. This study aims to review and analyze data from the literature about performance of VaMCI patients on the most used EF tests through a meta-analytic approach. Medline, Web of Knowledge and PsycINFO were searched, using the terms: "vascular mild cognitive impairment" OR "vascular cognitive impairment no dementia" OR "vascular mild neurocognitive disorder" AND "dysexecutive" OR "executive function". Meta-analyses were conducted for each of the selected tests, using random-effect models. Systematic review showed major discrepancies among the results of the studies included. Meta-analyses evidenced poorer performance on the Trail-Making Test part B and the Stroop color test by VaMCI patients compared to controls. A continuum of EF impairments has been proposed in SVCI. Early deficits appear to occur in cognitive flexibility and inhibitory control.

  6. Time-Series Interactions of Gene Expression, Vascular Growth and Hemodynamics during Early Embryonic Arterial Development.

    Directory of Open Access Journals (Sweden)

    Selda Goktas

    Full Text Available The role of hemodynamic forces within the embryo as biomechanical regulators for cardiovascular morphogenesis, growth, and remodeling is well supported through the experimental studies. Furthermore, clinical experience suggests that perturbed flow disrupts the normal vascular growth process as one etiology for congenital heart diseases (CHD and for fetal adaptation to CHD. However, the relationships between hemodynamics, gene expression and embryonic vascular growth are poorly defined due to the lack of concurrent, sequential in vivo data. In this study, a long-term, time-lapse optical coherence tomography (OCT imaging campaign was conducted to acquire simultaneous blood velocity, pulsatile micro-pressure and morphometric data for 3 consecutive early embryonic stages in the chick embryo. In conjunction with the in vivo growth and hemodynamics data, in vitro reverse transcription polymerase chain reaction (RT-PCR analysis was performed to track changes in transcript expression relevant to histogenesis and remodeling of the embryonic arterial wall. Our non-invasive extended OCT imaging technique for the microstructural data showed continuous vessel growth. OCT data coupled with the PIV technique revealed significant but intermitted increases in wall shear stress (WSS between first and second assigned stages and a noticeable decrease afterwards. Growth rate, however, did not vary significantly throughout the embryonic period. Among all the genes studied, only the MMP-2 and CASP-3 expression levels remained unchanged during the time course. Concurrent relationships were obtained among the transcriptional modulation of the genes, vascular growth and hemodynamics-related changes. Further studies are indicated to determine cause and effect relationships and reversibility between mechanical and molecular regulation of vasculogenesis.

  7. Nlrp3 prevents early renal interstitial edema and vascular permeability in unilateral ureteral obstruction.

    Directory of Open Access Journals (Sweden)

    Wilco P Pulskens

    Full Text Available Progressive renal disease is characterized by tubulo-interstitial injury with ongoing inflammation and fibrosis. The Nlrp3 inflammasome contributes to these pathophysiological processes through its canonical effects in cytokine maturation. Nlrp3 may additionally exert inflammasome-independent effects following tissue injury. Hence, in this study we investigated potential non-canonical effects of Nlrp3 following progressive renal injury by subjecting WT and Nlrp3-deficient (-/- mice to unilateral ureter obstruction (UUO. Our results revealed a progressive increase of renal Nlrp3 mRNA in WT mice following UUO. The absence of Nlrp3 resulted in enhanced tubular injury and dilatation and an elevated expression of injury biomarker NGAL after UUO. Moreover, interstitial edema was significantly elevated in Nlrp3-/- mice. This could be explained by increased intratubular pressure and an enhanced tubular and vascular permeability. In accordance, renal vascular leakage was elevated in Nlrp3-/- mice that associated with reduced mRNA expression of intercellular junction components. The decreased epithelial barrier function in Nlrp3-/- mice was not associated with increased apoptosis and/or proliferation of renal epithelial cells. Nlrp3 deficiency did not affect renal fibrosis or inflammation. Together, our data reveal a novel non-canonical effect of Nlrp3 in preserving renal integrity and protection against early tubular injury and interstitial edema following progressive renal injury.

  8. Vascular responses to radiotherapy and androgendeprivation therapy in experimental prostate cancer

    LENUS (Irish Health Repository)

    2012-05-23

    AbstractBackgroundRadiotherapy (RT) and androgen-deprivation therapy (ADT) are standard treatments for advanced prostate cancer (PC). Tumor vascularization is recognized as an important physiological feature likely to impact on both RT and ADT response, and this study therefore aimed to characterize the vascular responses to RT and ADT in experimental PC.MethodsUsing mice implanted with CWR22 PC xenografts, vascular responses to RT and ADT by castration were visualized in vivo by DCE MRI, before contrast-enhancement curves were analyzed both semi-quantitatively and by pharmacokinetic modeling. Extracted image parameters were correlated to the results from ex vivo quantitative fluorescent immunohistochemical analysis (qIHC) of tumor vascularization (9 F1), perfusion (Hoechst 33342), and hypoxia (pimonidazole), performed on tissue sections made from tumors excised directly after DCE MRI.ResultsCompared to untreated (Ctrl) tumors, an improved and highly functional vascularization was detected in androgen-deprived (AD) tumors, reflected by increases in DCE MRI parameters and by increased number of vessels (VN), vessel density ( VD), and vessel area fraction ( VF) from qIHC. Although total hypoxic fractions ( HF) did not change, estimated acute hypoxia scores ( AHS) – the proportion of hypoxia staining within 50 μm from perfusion staining – were increased in AD tumors compared to in Ctrl tumors. Five to six months after ADT renewed castration-resistant (CR) tumor growth appeared with an even further enhanced tumor vascularization. Compared to the large vascular changes induced by ADT, RT induced minor vascular changes. Correlating DCE MRI and qIHC parameters unveiled the semi-quantitative parameters area under curve ( AUC) from initial time-points to strongly correlate with VD and VF, whereas estimation of vessel size ( VS) by DCE MRI required pharmacokinetic modeling. HF was not correlated to any DCE MRI parameter, however, AHS may be estimated after

  9. Vascular responses to radiotherapy and androgen-deprivation therapy in experimental prostate cancer

    International Nuclear Information System (INIS)

    Røe, Kathrine; Mikalsen, Lars TG; Kogel, Albert J van der; Bussink, Johan; Lyng, Heidi; Ree, Anne H; Marignol, Laure; Olsen, Dag R

    2012-01-01

    Radiotherapy (RT) and androgen-deprivation therapy (ADT) are standard treatments for advanced prostate cancer (PC). Tumor vascularization is recognized as an important physiological feature likely to impact on both RT and ADT response, and this study therefore aimed to characterize the vascular responses to RT and ADT in experimental PC. Using mice implanted with CWR22 PC xenografts, vascular responses to RT and ADT by castration were visualized in vivo by DCE MRI, before contrast-enhancement curves were analyzed both semi-quantitatively and by pharmacokinetic modeling. Extracted image parameters were correlated to the results from ex vivo quantitative fluorescent immunohistochemical analysis (qIHC) of tumor vascularization (9 F1), perfusion (Hoechst 33342), and hypoxia (pimonidazole), performed on tissue sections made from tumors excised directly after DCE MRI. Compared to untreated (Ctrl) tumors, an improved and highly functional vascularization was detected in androgen-deprived (AD) tumors, reflected by increases in DCE MRI parameters and by increased number of vessels (VN), vessel density (VD), and vessel area fraction (VF) from qIHC. Although total hypoxic fractions (HF) did not change, estimated acute hypoxia scores (AHS) – the proportion of hypoxia staining within 50 μm from perfusion staining – were increased in AD tumors compared to in Ctrl tumors. Five to six months after ADT renewed castration-resistant (CR) tumor growth appeared with an even further enhanced tumor vascularization. Compared to the large vascular changes induced by ADT, RT induced minor vascular changes. Correlating DCE MRI and qIHC parameters unveiled the semi-quantitative parameters area under curve (AUC) from initial time-points to strongly correlate with VD and VF, whereas estimation of vessel size (VS) by DCE MRI required pharmacokinetic modeling. HF was not correlated to any DCE MRI parameter, however, AHS may be estimated after pharmacokinetic modeling. Interestingly, such

  10. Autonomic response to exercise as measured by cardio- vascular ...

    African Journals Online (AJOL)

    estimate the involvement of the autonomic nervous system (ANS) influence and balance in ... activity in response to exercise, training and overtraining. This ..... However, a lower HR and higher values for time domain HRV indicators were ...

  11. Clinical outcome and microvascular blood flow in VAC® - and Sorbalgon® -treated peri-vascular infected wounds in the groin after vascular surgery - an early interim analysis.

    Science.gov (United States)

    Acosta, Stefan; Monsen, Christina; Dencker, Magnus

    2013-08-01

    Vacuum-assisted wound closure (VAC(®)) therapy is considered to be superior to conventional dressings in the treatment of peri-vascular groin infections after vascular surgery at our department. Therefore, we performed an early interim analysis of the clinical outcomes in these seriously ill patients at risk of amputation and death. Patients were randomised to either VAC(®) (n = 5) or Sorbalgon(®) (n = 5; best alternative treatment) therapy after surgical debridement. Non-invasive, laser Doppler perfusion imaging (LDPI) studies of the skin adjacent to the undressed wound were performed after 14 days of wound treatment. There was no difference in LDPI values in VAC(®) versus Sorbalgon(®) treated patients (P = 0·46). One patient in the VAC(®) group suffered from two re-bleeding episodes, leading to vascular resection and transfemoral amputation and in the Sorbalgon(®) group two had a complete wound healing time of more than 4 months and one had a visible interposition bypass graft in the groin after 1 month of treatment. No patient died of the groin infection. Although not statistically proven, fewer wound treatment failures were recorded in the VAC(®) group, justifying this early interim analysis. LDPI studies were feasible. © 2012 The Authors. International Wound Journal © 2012 John Wiley & Sons Ltd and Medicalhelplines.com Inc.

  12. Ophthalmic Vascular Events after Primary Unilateral Intra-arterial Chemotherapy for Retinoblastoma in Early and Recent Eras.

    Science.gov (United States)

    Dalvin, Lauren A; Ancona-Lezama, David; Lucio-Alvarez, J Antonio; Masoomian, Babak; Jabbour, Pascal; Shields, Carol L

    2018-06-16

    To assess risk factors for ophthalmic vascular events after intra-arterial chemotherapy (IAC) for retinoblastoma. Retrospective cohort study. Patients who received unilateral IAC as primary treatment for retinoblastoma from January 1, 2009, to November 30, 2017, at a single center. Records were reviewed for patient demographics, tumor features, IAC parameters, and treatment-related vascular events in the early IAC era (2009-2011) compared with the recent era (2012-2017) using the t test and Fisher exact test. Change in event rates over time was assessed using Poisson regression analysis, with Spearman's rho used to test correlation. Rate of IAC-induced ophthalmic vascular events. There were 243 chemotherapy infusions in 76 eyes of 76 patients, divided into early (22 eyes, 57 infusions) and recent (54 eyes, 186 infusions) eras. Intra-arterial chemotherapy consisted of melphalan (243 infusions), topotecan (124 infusions), and carboplatin (9 infusions). A comparison (early vs. recent era) revealed fewer mean number of infusions (2.6 vs. 3.4, P = 0.02) with similar mean patient age and presenting tumor features. Event rates decreased over time (P early era vs. recent era) in the recent era (59% vs. 9% per eye, 23% vs. 3% per infusion, P age (P = 0.75), tumor diameter (P = 0.32), tumor thickness (P = 0.59), or cumulative dosage of melphalan (P = 0.13) or topotecan (P = 0.59). There were no IAC-induced vascular events in 72 infusions of 21 consecutively treated eyes in 2016 to 2017. Ophthalmic vascular events after IAC have decreased from the early era (2009-2011) through the current era (2012-2017) at this center. Experience performing this highly specialized procedure could be an important factor predicting IAC-related vascular events. Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  13. Effect of nabumetone treatment on vascular responses of the thoracic aorta in rat experimental arthritis.

    Science.gov (United States)

    Ulker, S; Onal, A; Hatip, F B; Sürücü, A; Alkanat, M; Koşay, S; Evinç, A

    2000-04-01

    Nabumetone is a nonsteroidal anti-inflammatory (NSAI) drug which is known to cause less gastrointestinal damage than other NSAI drugs. This study was performed to evaluate whether nabumetone treatment might alter the vascular aberrations related to inflammation in a rat model of adjuvant-induced arthritis. Nabumetone treatment (120 or 240 mg x kg(-1) x day(-1), orally) was initiated on the 15th day of adjuvant inoculation and continued for 14 days. Arthritic lesions, vascular contractile and relaxant responses and gastroduodenal histopathological preparations were evaluated 29 days after adjuvant inoculation. The contractile responses of aortic rings to phenylephrine and KCl were increased in grade 2 arthritic rats. In grade 3 arthritis only the phenylephrine contractility was decreased. The relaxant responses to acetylcholine and sodium nitroprusside were decreased in grades 2 and 3. In healthy rats, nabumetone did not change the vascular responses. After treatment of arthritic rats with nabumetone, both the contractile and relaxant response of the aortic rings returned to normal, and arthritic score and paw swelling were reduced. Gastroduodenal histopathology did not show erosions or ulcers in any of the groups. In conclusion, nabumetone improved the systemic signs and vascular alterations in experimental arthritis without showing any gastrointestinal side effects. Copyright 2000 S. Karger AG, Basel.

  14. The pars intermedia: an anatomic basis for a coordinated vascular response to female genital arousal.

    Science.gov (United States)

    Shih, Cheryl; Cold, Christopher J; Yang, Claire C

    2013-06-01

    The pars intermedia is an area of the vulva that has been inconsistently described in the literature. We conducted anatomic studies to better describe the tissues and vascular structures of the pars intermedia and proposed a functional rationale of the pars intermedia in the female sexual response. Nine cadaveric vulvectomy specimens were used. Each was serially sectioned and stained with hematoxylin and eosin and Masson's trichrome. Histologic ultrastructural description of the pars intermedia. The pars intermedia contains veins traveling longitudinally in the angle of the clitoris, supported by collagen-rich stromal tissues. These veins drain the different vascular compartments of the vulva, including the clitoris, the bulbs, and labia minora; also, the interconnecting veins link the different vascular compartments. The pars intermedia is not composed of erectile tissue, distinguishing it from the erectile tissues of the corpora cavernosa of the clitoris as well as the corpus spongiosum of the clitoral (vestibular) bulbs. The venous communications of the pars intermedia, linking the erectile tissues with the other vascular compartments of the vulva, appear to provide the anatomic basis for a coordinated vascular response during female sexual arousal. © 2012 International Society for Sexual Medicine.

  15. Measures of total stress-induced blood pressure responses are associated with vascular damage.

    Science.gov (United States)

    Nazzaro, Pietro; Seccia, Teresa; Vulpis, Vito; Schirosi, Gabriella; Serio, Gabriella; Battista, Loredana; Pirrelli, Anna

    2005-09-01

    The role of cardiovascular reactivity to study hypertension, and the assessment methods, are still controversial. We aimed to verify the association of hypertension and vascular damage with several measures of cardiovascular response. We studied 40 patients with normal-high (132 +/- 1/87 +/- 1 mm Hg) blood pressure (Group 1) and 80 untreated hypertensive subjects. Postischemic forearm vascular resistance (mFVR) served to differentiate hypertensive subjects (142 +/- 2/92 +/- 1 mm Hg v 143 +/- 2/94 +/- 2 mm Hg, P = NS) with a lower (Group 2) and higher (Group 3) hemodynamic index of vascular damage (4.8 +/- .05 v 6.3 +/- .09, P blood pressure, heart rate, forearm blood flow, and vascular resistance. Reactivity measures included: a) change from baseline, b) residualized score, c) cumulative change from baseline and residualized score, and d) total reactivity as area-under-the-curve (AUC), including changes occurring during baseline and recovery phases. The AUC of systolic blood pressure, diastolic blood pressure, and mFVR progressively increased in the groups (P AUC of SBP, DBP, and forearm blood flow and resistance demonstrated the highest (P AUC of SBP (beta = 0.634) and forearm blood flow (beta = -0.337) were predictive (P blood pressure stress response, as AUC, including baseline and recovery phases, was significantly better associated with hypertension and vascular damage than the other reactivity measures studied.

  16. Hormonal responses during early embryogenesis in maize.

    Science.gov (United States)

    Chen, Junyi; Lausser, Andreas; Dresselhaus, Thomas

    2014-04-01

    Plant hormones have been shown to regulate key processes during embryogenesis in the model plant Arabidopsis thaliana, but the mechanisms that determine the peculiar embryo pattern formation of monocots are largely unknown. Using the auxin and cytokinin response markers DR5 and TCSv2 (two-component system, cytokinin-responsive promoter version #2), as well as the auxin efflux carrier protein PIN1a (PINFORMED1a), we have studied the hormonal response during early embryogenesis (zygote towards transition stage) in the model and crop plant maize. Compared with the hormonal response in Arabidopsis, we found that detectable hormone activities inside the developing maize embryo appeared much later. Our observations indicate further an important role of auxin, PIN1a and cytokinin in endosperm formation shortly after fertilization. Apparent auxin signals within adaxial endosperm cells and cytokinin responses in the basal endosperm transfer layer as well as chalazal endosperm are characteristic for early seed development in maize. Moreover, auxin signalling in endosperm cells is likely to be involved in exogenous embryo patterning as auxin responses in the endosperm located around the embryo proper correlate with adaxial embryo differentiation and outgrowth. Overall, the comparison between Arabidopsis and maize hormone response and flux suggests intriguing mechanisms in monocots that are used to direct their embryo patterning, which is significantly different from that of eudicots.

  17. Tailoring the foreign body response for in situ vascular tissue engineering

    NARCIS (Netherlands)

    Rothuizen, T.C.; Damanik, Febriyani; Anderson, J.; Lavrijsen, T.; Cox, M.A.J.; Rabelink, T.J.; Moroni, Lorenzo; Rotmans, J.

    2015-01-01

    This study describes a screening platform for a guided in situ vascular tissue engineering approach. Polymer rods were developed that upon 3 weeks of subcutaneous implantation evoke a controlled inflammatory response culminating in encapsulation by a tube-shaped autologous fibrocellular tissue

  18. Inflammation and vascular responses to acute mental stress : implications for the triggering of myocardial infarction

    NARCIS (Netherlands)

    Paine, N.J.; Bosch, J.A.; Veldhuijzen Van Zanten, J.J.C.S.

    2012-01-01

    There is evidence that mental stress can trigger myocardial infarction. Even though the underlying mechanisms remain to be determined, both inflammation and vascular responses to mental stress have been implicated as contributing factors. This review explores the effects of inflammation on the

  19. Uric acid promotes vascular stiffness, maladaptive inflammatory responses and proteinuria in western diet fed mice.

    Science.gov (United States)

    Aroor, Annayya R; Jia, Guanghong; Habibi, Javad; Sun, Zhe; Ramirez-Perez, Francisco I; Brady, Barron; Chen, Dongqing; Martinez-Lemus, Luis A; Manrique, Camila; Nistala, Ravi; Whaley-Connell, Adam T; Demarco, Vincent G; Meininger, Gerald A; Sowers, James R

    2017-09-01

    Aortic vascular stiffness has been implicated in the development of cardiovascular disease (CVD) and chronic kidney disease (CKD) in obese individuals. However, the mechanism promoting these adverse effects are unclear. In this context, promotion of obesity through consumption of a western diet (WD) high in fat and fructose leads to excess circulating uric acid. There is accumulating data implicating elevated uric acid in the promotion of CVD and CKD. Accordingly, we hypothesized that xanthine oxidase(XO) inhibition with allopurinol would prevent a rise in vascular stiffness and proteinuria in a translationally relevant model of WD-induced obesity. Four-week-old C57BL6/J male mice were fed a WD with excess fat (46%) and fructose (17.5%) with or without allopurinol (125mg/L in drinking water) for 16weeks. Aortic endothelial and extracellular matrix/vascular smooth muscle stiffness was evaluated by atomic force microscopy. Aortic XO activity, 3-nitrotyrosine (3-NT) and aortic endothelial sodium channel (EnNaC) expression were evaluated along with aortic expression of inflammatory markers. In the kidney, expression of toll like receptor 4 (TLR4) and fibronectin were assessed along with evaluation of proteinuria. XO inhibition significantly attenuated WD-induced increases in plasma uric acid, vascular XO activity and oxidative stress, in concert with reductions in proteinuria. Further, XO inhibition prevented WD-induced increases in aortic EnNaC expression and associated endothelial and subendothelial stiffness. XO inhibition also reduced vascular pro-inflammatory and maladaptive immune responses induced by consumption of a WD. XO inhibition also decreased WD-induced increases in renal TLR4 and fibronectin that associated proteinuria. Consumption of a WD leads to elevations in plasma uric acid, increased vascular XO activity, oxidative stress, vascular stiffness, and proteinuria all of which are attenuated with allopurinol administration. Copyright © 2017 Elsevier Inc

  20. Changes in forearm muscle temperature alter renal vascular responses to isometric handgrip.

    Science.gov (United States)

    Kuipers, Nathan T; Sauder, Charity L; Kearney, Matthew L; Ray, Chester A

    2007-12-01

    The purpose of the present study was to examine the effect of heating and cooling the forearm muscles on renal vascular responses to ischemic isometric handgrip (IHG). It was hypothesized that heating and cooling the forearm would augment and attenuate, respectively, renal vascular responses to IHG. Renal vascular responses to IHG were studied during forearm heating at 39 degrees C (n = 15, 26 +/- 1 yr) and cooling at 26 degrees C (n = 12, 26 +/- 1 yr). For a control trial, subjects performed the experimental protocol while the forearm was normothermic (approximately 34 degrees C). Muscle temperature (measured by intramuscular probe) was controlled by changing the temperature of water cycling through a water-perfused sleeve. The experimental protocol was as follows: 3 min at baseline, 1 min of ischemia, ischemic IHG to fatigue, and 2 min of postexercise muscle ischemia. At rest, renal artery blood velocity (RBV; Doppler ultrasound) and renal vascular conductance (RVC = RBV/mean arterial blood pressure) were not different between normothermia and the two thermal conditions. During ischemic IHG, there were greater decreases in RBV and RVC in the heating trial. However, RBV and RVC were similar during postexercise muscle ischemia during heating and normothermia. RVC decreased less during cooling than in normothermia while the subjects performed the ischemic IHG protocol. During postexercise muscle ischemia, RVC was greater during cooling than in normothermia. These results indicate that heating augments mechanoreceptor-mediated renal vasoconstriction whereas cooling blunts metaboreceptor-mediated renal vasoconstriction.

  1. Near-infrared spectroscopy assessment of microvasculature detects difference in lower limb vascular responsiveness in obese compared to lean individuals.

    Science.gov (United States)

    Soares, Rogério Nogueira; Murias, Juan M

    2018-07-01

    Microvascular dysfunction is an early complication in obesity-related cardiovascular disease (CVD) that can lead to changes in hemodynamic function and endothelial cell expression throughout the vasculature that is vessel specific. This study aimed to evaluate whether the near-infrared spectroscopy (NIRS) combined with a vascular occlusion (VOT) assessment was capable of detecting differences in vascular responsiveness within the microvasculature of the lower limb between lean and obese individuals. Twenty lean (BMI = 21.6 ± 1.3) and 17 obese individuals (BMI = 33.9 ± 1.1) participated in the study. Individuals underwent a VOT (5 min of baseline, 5 min of occlusion, and 8 min following cuff release) and vascular responsiveness was evaluated by the Slope 2 (Slope 2 StO 2 ) and the area under the curve (StO 2AUC ) of oxygen saturation (StO 2 ) signal during reperfusion. The difference between the minimal and the maximal value of StO 2 was calculated as the Amplitude of the StO 2 response. The Slope 2 StO 2 of the obese individuals was smaller (0.68 ± 0.07%·s -1 ) than the Slope 2 StO 2 of the lean individuals (1.08 ± 0.13%·s -1 ;P lean individuals (1708 ± 168%·s -1 ; P lean ones (30.4 ± 2.9 vs 21.6 ± 1.3 StO 2 (%), respectively; P lean individuals (r = 0.745; P lean and obese individuals. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Origin and Evolution of The Early- Silurian Land Vascular Plants: Evidence From Biomarkers

    Science.gov (United States)

    Jin, R.

    2016-12-01

    Origin and early evolution of land vascular plants, is one of the most intriguing hotspots in the life science research. During the 1970s and 1980s,Pinnatiramosus qianensis was found in early-Silurian strata in guizhou of south China.43 years have passed. But so far, the biological characteristics and belonging of the age of this unique plant have been debated again and again, up in the air.Biomarkers have a good stability in the process of organic evolution, no more or less changed, so they have a special `function of mark'. While biomarkers can provide information about organic matter of hydrocarbon source rock (the source), the period of deposition and burial (diagenesis) environmental conditions, and many other aspects of information.This paper obtained the sedimentary environment, source of organic matter input and other relevant information, through extracting and analyzing biomarkers of the 26 samples in the late Ordovician to early Silurian strata in NorthGuizhou areas. According to the results, Pr/Ph of late Ordovician Meitan Fm-early Silurian Hanjiadian Fm is high.It manifests more pristane, characterized by reductive environment. At the bottom of the Hanjiadian Fm, Pr/Ph has a volatility.Some huge environmental changes may have taken place in the corresponding period. N-alkanes do not have parity advantage or has even carbon advantage slightly.The peak carbon is mainly in low carbon number.(C21 + C22)/(C28 + C29) is high.Aquatic organisms is a major source of organic matter during this period,C21-/C22+ is low.This may be caused by the relatively serious loss of light hydrocarbon during the separation of components. In the Hanjiadian Fm,information of C29/C27 sterane ratios and oleanane index showed a trend of rising at the same time, indicating that during this period, there was a gradual increase input in the number of higher plants.The stable carbon isotope of saturated hydrocarbon and aromatic hydrocarbon in the Hanjiadian Fm also gradually become

  3. The Concept of Early Vascular Ageing – An Update in 2015

    Directory of Open Access Journals (Sweden)

    Peter M. Nilsson

    2015-11-01

    Full Text Available Arterial ageing is a process that can be quantified, at least to some degree, by measurement of pulse wave velocity along the aorta, the largest elastic artery, as a marker of arterial stiffness. In recent years the new concept of early vascular ageing (EVA has been developed by a group of mostly European researchers and some reviews have been published. Based on a lecture given at the European Association for the Study of Diabetes (EASD Meeting in Vienna 2014, this review was written to describe recent developments in research dedicated to EVA and new emerging aspects found in studies of families at high cardiovascular (CV risk. This brings new perspectives related to genetics, telomere biology, and the role of gut microbiota. Even if EVA has been described in general terms there is still no unifying definition available and no direct treatment, only recommendations for conventional CV risk factor control. However, a new intervention study (SPARTE is ongoing in France with a randomised design to treat arterial stiffness in patients with hypertension versus conventional treatment strategies. Results are expected in a few years and will be of importance in defining the role of arterial stiffness, a core feature of EVA, as a target for treatment.

  4. Transhepatic Hilar Approach for Perihilar Cholangiocarcinoma: Significance of Early Judgment of Resectability and Safe Vascular Reconstruction.

    Science.gov (United States)

    Kuriyama, Naohisa; Isaji, Shuji; Tanemura, Akihiro; Iizawa, Yusuke; Kato, Hiroyuki; Murata, Yasuhiro; Azumi, Yoshinori; Kishiwada, Masashi; Mizuno, Shugo; Usui, Masanobu; Sakurai, Hiroyuki

    2017-03-01

    In the most common surgical procedure for perihilar cholangiocarcinoma, the margin status of the proximal bile duct is determined at the final step. Our procedure, the transhepatic hilar approach, confirms a cancer-negative margin status of the proximal bile duct first. We first performed a partial hepatic parenchymal transection to expose the hilar plate, and then transected the proximal bile duct to confirm margin status. Then, divisions of the hepatic artery and portal vein of the future resected liver are performed, followed by the residual hepatic parenchymal transection. The transhepatic hilar approach offers a wide surgical field for safe resection and reconstruction of the portal vein in the middle of the hepatectomy. We reviewed 23 patients with perihilar cholangiocarcinoma who underwent major hepatectomy using our procedure from 2011 to 2015. A combined vascular resection and reconstruction was carried out in 14 patients (60.9%). R0 resection was achieved in 17 patients (73.9%), and the overall 3-year survival rate was 52.9% (median survival time 52.4 months). The transhepatic hilar approach is useful and practicable regardless of local tumor extension, enabling us to determine tumor resectability and perform safe resection and reconstruction of the portal vein early in the operation.

  5. Vascular Response of Ruthenium Tetraamines in Aortic Ring from Normotensive Rats

    Directory of Open Access Journals (Sweden)

    Ana Gabriela Conceição-Vertamatti

    2015-03-01

    Full Text Available Background: Ruthenium (Ru tetraamines are being increasingly used as nitric oxide (NO carriers. In this context, pharmacological studies have become highly relevant to better understand the mechanism of action involved. Objective: To evaluate the vascular response of the tetraamines trans-[RuII(NH34(Py(NO]3+, trans-[RuII(Cl(NO (cyclan](PF62, and trans-[RuII(NH34(4-acPy(NO]3+. Methods: Aortic rings were contracted with noradrenaline (10−6 M. After voltage stabilization, a single concentration (10−6 M of the compounds was added to the assay medium. The responses were recorded during 120 min. Vascular integrity was assessed functionally using acetylcholine at 10−6 M and sodium nitroprusside at 10−6 M as well as by histological examination. Results: Histological analysis confirmed the presence or absence of endothelial cells in those tissues. All tetraamine complexes altered the contractile response induced by norepinephrine, resulting in increased tone followed by relaxation. In rings with endothelium, the inhibition of endothelial NO caused a reduction of the contractile effect caused by pyridine NO. No significant responses were observed in rings with endothelium after treatment with cyclan NO. In contrast, in rings without endothelium, the inhibition of guanylate cyclase significantly reduced the contractile response caused by the pyridine NO and cyclan NO complexes, and both complexes caused a relaxing effect. Conclusion: The results indicate that the vascular effect of the evaluated complexes involved a decrease in the vascular tone induced by norepinephrine (10−6 M at the end of the incubation period in aortic rings with and without endothelium, indicating the slow release of NO from these complexes and suggesting that the ligands promoted chemical stability to the molecule. Moreover, we demonstrated that the association of Ru with NO is more stable when the ligands pyridine and cyclan are used in the formulation of the compound.

  6. Dissociation between neural and vascular responses to sympathetic stimulation : contribution of local adrenergic receptor function

    Science.gov (United States)

    Jacob, G.; Costa, F.; Shannon, J.; Robertson, D.; Biaggioni, I.

    2000-01-01

    Sympathetic activation produced by various stimuli, eg, mental stress or handgrip, evokes regional vascular responses that are often nonhomogeneous. This phenomenon is believed to be the consequence of the recruitment of differential central neural pathways or of a sympathetically mediated vasodilation. The purpose of this study was to determine whether a similar heterogeneous response occurs with cold pressor stimulation and to test the hypothesis that local differences in adrenergic receptor function could be in part responsible for this diversity. In 8 healthy subjects, local norepinephrine spillover and blood flow were measured in arms and legs at baseline and during sympathetic stimulation induced by baroreflex mechanisms (nitroprusside infusion) or cold pressor stimulation. At baseline, legs had higher vascular resistance (27+/-5 versus 17+/-2 U, P=0.05) despite lower norepinephrine spillover (0.28+/-0.04 versus 0.4+/-0.05 mg. min(-1). dL(-1), P=0.03). Norepinephrine spillover increased similarly in both arms and legs during nitroprusside infusion and cold pressor stimulation. On the other hand, during cold stimulation, vascular resistance increased in arms but not in legs (20+/-9% versus -7+/-4%, P=0.03). Increasing doses of isoproterenol and phenylephrine were infused intra-arterially in arms and legs to estimate beta-mediated vasodilation and alpha-induced vasoconstriction, respectively. beta-Mediated vasodilation was significantly lower in legs compared with arms. Thus, we report a dissociation between norepinephrine spillover and vascular responses to cold stress in lower limbs characterized by a paradoxical decrease in local resistance despite increases in sympathetic activity. The differences observed in adrenergic receptor responses cannot explain this phenomenon.

  7. Early Screening for Tetrahydrobiopterin Responsiveness in Phenylketonuria.

    Science.gov (United States)

    Porta, Francesco; Spada, Marco; Ponzone, Alberto

    2017-08-01

    Since 2007, synthetic tetrahydrobiopterin (BH4) has been approved as a therapeutic option in BH4-responsive phenylketonuria (PKU) and since 2015 extended to infants younger than 4 years in Europe. The current definition of BH4 responsiveness relies on the observation of a 20% to 30% blood phenylalanine (Phe) decrease after BH4 administration, under nonstandardized conditions. By this definition, however, patients with the same genotype or even the same patients were alternatively reported as responsive or nonresponsive to the cofactor. These inconsistencies are troubling, as frustrating patient expectations and impairing cost-effectiveness of BH4-therapy. Here we tried a quantitative procedure through the comparison of the outcome of a simple Phe and a combined Phe plus BH4 loading in a series of infants with PKU, most of them harboring genotypes already reported as BH4 responsive. Under these ideal conditions, blood Phe clearance did not significantly differ after the 2 types of loading, and a 20% to 30% decrease of blood Phe occurred irrespective of BH4 administration in milder forms of PKU. Such early screening for BH4 responsiveness, based on a quantitative assay, is essential for warranting an evidence-based and cost-effective therapy in those patients with PKU eventually but definitely diagnosed as responsive to the cofactor. Copyright © 2017 by the American Academy of Pediatrics.

  8. Prediction of heat-illness symptoms with the prediction of human vascular response in hot environment under resting condition.

    Science.gov (United States)

    Aggarwal, Yogender; Karan, Bhuwan Mohan; Das, Barsa Nand; Sinha, Rakesh Kumar

    2008-04-01

    The thermoregulatory control of human skin blood flow is vital to maintain the body heat storage during challenges of thermal homeostasis under heat stress. Whenever thermal homeostasis disturbed, the heat load exceeds heat dissipation capacity, which alters the cutaneous vascular responses along with other body physiological variables. Whole body skin blood flow has been calculated from the forearm blood flow. Present model has been designed using electronics circuit simulator (Multisim 8.0, National Instruments, USA), is to execute a series of predictive equations for early prediction of physiological parameters of young nude subjects during resting condition at various level of dry heat stress under almost still air to avoid causalities associated with hot environmental. The users can execute the model by changing the environmental temperature in degrees C and exposure time in minutes. The model would be able to predict and detect the changes in human vascular responses along with other physiological parameters and from this predicted values heat related-illness symptoms can be inferred.

  9. Post-treatment vascular leakage and inflammatory responses around brain cysts in porcine neurocysticercosis.

    Directory of Open Access Journals (Sweden)

    Siddhartha Mahanty

    2015-03-01

    Full Text Available Cysticidal treatment of neurocysticercosis, an infection of humans and pig brains with Taenia solium, results in an early inflammatory response directed to cysts causing seizures and focal neurological manifestations. Treatment-induced pericystic inflammation and its association with blood brain barrier (BBB dysfunction, as determined by Evans blue (EB extravasation, was studied in infected untreated and anthelmintic-treated pigs. We compared the magnitude and extent of the pericystic inflammation, presence of EB-stained capsules, the level of damage to the parasite, expression of genes for proinflammatory and regulatory cytokines, chemokines, and tissue remodeling by quantitative PCR assays between treated and untreated infected pigs and between EB-stained (blue and non stained (clear cysts. Inflammatory scores were higher in pericystic tissues from EB-stained cysts compared to clear cysts from untreated pigs and also from anthelmintic-treated pigs 48 hr and 120 hr after treatment. The degree of inflammation correlated with the severity of cyst wall damage and both increased significantly at 120 hours. Expression levels of the proinflammatory genes for IL-6, IFN-γ, TNF-α were higher in EB-stained cysts compared to clear cysts and unaffected brain tissues, and were generally highest at 120 hr. Additionally, expression of some markers of immunoregulatory activity (IL-10, IL-2Rα were decreased in EB-stained capsules. An increase in other markers for regulatory T cells (CTLA4, FoxP3 was found, as well as significant increases in expression of two metalloproteases, MMP1 and MMP2 at 48 hr and 120 hr post-treatment. We conclude that the increase in severity of the inflammation caused by treatment is accompanied by both a proinflammatory and a complex regulatory response, largely limited to pericystic tissues with compromised vascular integrity. Because treatment induced inflammation occurs in porcine NCC similar to that in human cases, this model

  10. The zinc transporter ZIP12 regulates the pulmonary vascular response to chronic hypoxia.

    Science.gov (United States)

    Zhao, Lan; Oliver, Eduardo; Maratou, Klio; Atanur, Santosh S; Dubois, Olivier D; Cotroneo, Emanuele; Chen, Chien-Nien; Wang, Lei; Arce, Cristina; Chabosseau, Pauline L; Ponsa-Cobas, Joan; Frid, Maria G; Moyon, Benjamin; Webster, Zoe; Aldashev, Almaz; Ferrer, Jorge; Rutter, Guy A; Stenmark, Kurt R; Aitman, Timothy J; Wilkins, Martin R

    2015-08-20

    The typical response of the adult mammalian pulmonary circulation to a low oxygen environment is vasoconstriction and structural remodelling of pulmonary arterioles, leading to chronic elevation of pulmonary artery pressure (pulmonary hypertension) and right ventricular hypertrophy. Some mammals, however, exhibit genetic resistance to hypoxia-induced pulmonary hypertension. We used a congenic breeding program and comparative genomics to exploit this variation in the rat and identified the gene Slc39a12 as a major regulator of hypoxia-induced pulmonary vascular remodelling. Slc39a12 encodes the zinc transporter ZIP12. Here we report that ZIP12 expression is increased in many cell types, including endothelial, smooth muscle and interstitial cells, in the remodelled pulmonary arterioles of rats, cows and humans susceptible to hypoxia-induced pulmonary hypertension. We show that ZIP12 expression in pulmonary vascular smooth muscle cells is hypoxia dependent and that targeted inhibition of ZIP12 inhibits the rise in intracellular labile zinc in hypoxia-exposed pulmonary vascular smooth muscle cells and their proliferation in culture. We demonstrate that genetic disruption of ZIP12 expression attenuates the development of pulmonary hypertension in rats housed in a hypoxic atmosphere. This new and unexpected insight into the fundamental role of a zinc transporter in mammalian pulmonary vascular homeostasis suggests a new drug target for the pharmacological management of pulmonary hypertension.

  11. Suppressive effects of lysozyme on polyphosphate-mediated vascular inflammatory responses

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Jiwoo [College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, Kyungpook National University, Daegu 41566 (Korea, Republic of); Ku, Sae-Kwang [Department of Anatomy and Histology, College of Korean Medicine, Daegu Haany University, Gyeongsan 38610 (Korea, Republic of); Lee, Suyeon [College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, Kyungpook National University, Daegu 41566 (Korea, Republic of); Bae, Jong-Sup, E-mail: baejs@knu.ac.kr [College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, Kyungpook National University, Daegu 41566 (Korea, Republic of)

    2016-06-10

    Lysozyme, found in relatively high concentration in blood, saliva, tears, and milk, protects us from the ever-present danger of bacterial infection. Previous studies have reported proinflammatory responses of endothelial cells to the release of polyphosphate(PolyP). In this study, we examined the anti-inflammatory responses and mechanisms of lysozyme and its effects on PolyP-induced septic activities in human umbilical vein endothelial cells (HUVECs) and mice. The survival rates, septic biomarker levels, behavior of human neutrophils, and vascular permeability were determined in PolyP-activated HUVECs and mice. Lysozyme suppressed the PolyP-mediated vascular barrier permeability, upregulation of inflammatory biomarkers, adhesion/migration of leukocytes, and activation and/or production of nuclear factor-κB, tumor necrosis factor-α, and interleukin-6. Furthermore, lysozyme demonstrated protective effects on PolyP-mediated lethal death and the levels of the related septic biomarkers. Therefore, these results indicated the therapeutic potential of lysozyme on various systemic inflammatory diseases, such as sepsis or septic shock. -- Highlights: •PolyP is shown to be an important mediator of vascular inflammation. •Lysozyme inhibited PolyP-mediated hyperpermeability. •Lysozyme inhibited PolyP-mediated septic response. •Lysozyme reduced PolyP-induced septic mortality.

  12. Postural vascular response in human skin: passive and active reactions to alteration of transmural pressure.

    Science.gov (United States)

    Jepsen, H; Gaehtgens, P

    1993-09-01

    Laser-Doppler (LD) fluxmetry was performed in the palmar finger skin of healthy subjects to study the mechanisms contributing to the postural vascular response. Local transmural pressure in the skin blood vessels of the region studied was altered for 1 min in two experimental series either by passive movement of the arm to different vertical hand positions relative to heart level or by application of external pressure (-120-180 mmHg) to the finger. Heart and respiratory rate, arterial blood pressure, and LD flux in the contralateral finger (kept at heart level) were measured. The measurements suggest a compound reaction of local (myogenic) and systemic (neurogenic) mechanisms: the local regulatory component appears as a graded active vascular response elicited by passive vessel distension or compression. A systemic component, associated with a single deep inspiration, is frequently observed during the actual movement of the arm. In addition, prolonged holding of the test hand in a given vertical position also elicits a delayed vascular response in the control hand at heart level, which may be generated by volume receptors in the intrathoracic low-pressure system.

  13. Suppressive effects of lysozyme on polyphosphate-mediated vascular inflammatory responses

    International Nuclear Information System (INIS)

    Chung, Jiwoo; Ku, Sae-Kwang; Lee, Suyeon; Bae, Jong-Sup

    2016-01-01

    Lysozyme, found in relatively high concentration in blood, saliva, tears, and milk, protects us from the ever-present danger of bacterial infection. Previous studies have reported proinflammatory responses of endothelial cells to the release of polyphosphate(PolyP). In this study, we examined the anti-inflammatory responses and mechanisms of lysozyme and its effects on PolyP-induced septic activities in human umbilical vein endothelial cells (HUVECs) and mice. The survival rates, septic biomarker levels, behavior of human neutrophils, and vascular permeability were determined in PolyP-activated HUVECs and mice. Lysozyme suppressed the PolyP-mediated vascular barrier permeability, upregulation of inflammatory biomarkers, adhesion/migration of leukocytes, and activation and/or production of nuclear factor-κB, tumor necrosis factor-α, and interleukin-6. Furthermore, lysozyme demonstrated protective effects on PolyP-mediated lethal death and the levels of the related septic biomarkers. Therefore, these results indicated the therapeutic potential of lysozyme on various systemic inflammatory diseases, such as sepsis or septic shock. -- Highlights: •PolyP is shown to be an important mediator of vascular inflammation. •Lysozyme inhibited PolyP-mediated hyperpermeability. •Lysozyme inhibited PolyP-mediated septic response. •Lysozyme reduced PolyP-induced septic mortality.

  14. Low Prevalence and Clinical Effect of Vascular Risk Factors in Early-Onset Alzheimer's Disease.

    Science.gov (United States)

    Chen, Yaohua; Sillaire, Adeline Rollin; Dallongeville, Jean; Skrobala, Emilie; Wallon, David; Dubois, Bruno; Hannequin, Didier; Pasquier, Florence

    2017-01-01

    Determinants of early-onset Alzheimer's disease (EOAD) are not well known. In late-onset AD, vascular risk factors (VRFs) are associated with earlier clinical manifestation. The objective of this study was to assess the putative association between VRFs and EOAD. We studied participants with dementia meeting criteria for EOAD (recruited into the French CoMAJ prospective cohort study from 1 June 2009 to 28 February 2014) and age-, gender-matched controls (ratio 1:3, drawn randomly from the French MONA-LISA population-based survey between 2005 and 2007). Demographic data, VRFs, comorbidities, treatments, and APOE genotypes were compared in multivariable logistic regression analyses. We studied 102 participants with dementia (mean±standard deviation age: 59.5±3.8; women: 59.8%) and 306 controls. Compared with controls, EOAD participants had spent less time in formal education (9.9±2.9 versus 11.7±3.8 y; p < 0.0001), were less likely to be regular alcohol consumers (p < 0.0001), had a lower body mass index (-2 kg/m2; p < 0.0004), and a lower mean systolic blood pressure (-6.2 mmHg; p = 0.0036). The prevalence of APOE ɛ4 allele was higher in participants with dementia than in controls (50% versus 29.4%; p = 0.0002), as was the prevalence of depression (48% versus 32%; p < 0.001). Similar results were observed in multivariable analysis. Compared with EOAD participants lacking VRFs, EOAD participants with at least one VRF had a higher prevalence of depression (29.6% versus 53.3%, respectively; p = 0.03). The prevalence of VRFs is not elevated in EOAD patients (in contrast to older AD patients). Extensive genetic testing should be considered more frequently in the context of EOAD.

  15. The effects of chronic resveratrol treatment on vascular responsiveness of streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Silan, Coskun

    2008-05-01

    Deficiency in the vasorelaxant capacity is a result of an oxidative stress in diabetic animals and seems to be an etiological factor of vascular complications of diabetes. The present study was designed to examine whether resveratrol (RSV), a polyphenolic compound which is naturally present in grape and red wine, has a protective effect on diabetic aorta. Resveratrol (5 mg/kg/d, i.p.) was administered for 42 d to streptozotocin (STZ) (60 mg/kg) induced diabetic rats. Loss of weight, hyperglycemia, and elevated levels of plasma malondialdehyde (MDA) were observed in diabetic rats. Resveratrol treatment was significantly effective for these metabolic and biochemical abnormalities. The contractile responses of the aorta were recorded. Compared with control subjects, the aorta showed significantly enhanced contractile responses to noradrenaline (NA), but not to potassium chloride (KCl), in diabetic rats. Treatment of diabetic rats with resveratrol significantly reversed the increases in responsiveness and sensitivity of aorta to noradrenaline. In diabetic aorta, the relaxation response to acetylcholine (Ach) was found to be significantly decreased compared with control subjects, and resveratrol treatment reversed this; no such change was observed in the relaxation response to sodium nitroprusside (SNP). These results indicated that resveratrol significantly improved not only glucose metabolism and oxidative injury but also impaired vascular responses in streptozotocin induced diabetic rats.

  16. Bone Morphogenetic Proteins 2/4 Are Upregulated during the Early Development of Vascular Calcification in Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Xiao Wei

    2018-01-01

    Full Text Available Vascular calcification is a main cause of increased cardiovascular morbidity and mortality in chronic kidney disease (CKD patients. This study aimed to investigate the role of the bone morphogenetic protein (BMP signaling pathway in the early development of vascular calcification in CKD. A CKD vascular calcification rat model was established by providing rats with a 1.8% high-phosphorus diet and an intragastric administration of 2.5% adenine suspension. The kidney and aortic pathologies were analyzed. Blood biochemical indicators, serum BMP-2 and BMP-4 levels, and aortic calcium content were determined. The expression levels of BMP-2, BMP-4, bone morphogenetic protein receptor-IA (BMPR-IA, and matrix Gla protein (MGP in aorta were examined by quantitative real-time polymerase chain reaction and immunohistochemistry. Compared with the normal control (Nor rats, the CKD rats exhibited a significantly decreased body weight and an increased kidney weight as well as abnormal renal function and calcium-phosphorus metabolism. Aortic von Kossa and Alizarin red staining showed massive granular deposition and formation of calcified nodules in aorta at 8 weeks. The aortic calcium content was significantly increased, which was positively correlated with the serum BMP-2 (r=0.929; P<0.01 and serum BMP-4 (r=0.702; P<0.01 levels in CKD rats. The rat aortic BMP-2 mRNA level in the CKD rats was persistently increased, and the BMP-4 mRNA level was prominently increased at the 4th week, declining thereafter. Strong staining of BMP-2, BMP-4, BMPR-IA, and MGP proteins was observed in the tunica media of the aorta from the 4th week after model induction. In conclusion, activation of the BMP signaling pathway is involved in the early development of vascular calcification in CKD. Therefore, elevated serum BMP-2 and BMP-4 levels may serve as serum markers for CKD vascular calcification.

  17. Exposure to Experimental Preeclampsia in Mice Enhances the Vascular Response to Future Injury

    Science.gov (United States)

    Pruthi, Dafina; Khankin, Eliyahu V.; Blanton, Robert M.; Aronovitz, Mark; Burke, Suzanne D.; McCurley, Amy; Karumanchi, S. Ananth; Jaffe, Iris Z.

    2015-01-01

    Cardiovascular disease (CVD) remains the leading killer of women in developed nations. One gender-specific risk factor is preeclampsia (PE), a syndrome of hypertension and proteinuria that complicates 5% of pregnancies. Although PE resolves after delivery, exposed women are at increased long term risk of premature CVD and mortality. Preexisting CVD risk factors are associated with increased risk of developing PE but whether PE merely uncovers risk or contributes directly to future CVD remains a critical unanswered question. A mouse PE model was used to test the hypothesis that PE causes an enhanced vascular response to future vessel injury. A PE-like state was induced in pregnant CD1 mice by overexpressing soluble fms-like tyrosine kinase-1 (sFlt-1), a circulating anti-angiogenic protein that induces hypertension and glomerular disease resembling human PE. Two months post-partum, sFlt-1 levels and blood pressure normalized and cardiac size and function by echocardiography and renal histology were indistinguishable in PE-exposed compared to control mice. Mice were then challenged with unilateral carotid injury. PE-exposed mice had significantly enhanced vascular remodeling with increased vascular smooth muscle cell proliferation (180% increase, P<0.01) and vessel fibrosis (216% increase, P<0.001) compared to control pregnancy. In the contralateral uninjured vessel, there was no difference in remodeling after exposure to PE. These data support a new model in which vessels exposed to PE retain a persistently enhanced vascular response to injury despite resolution of PE after delivery. This new paradigm may contribute to the substantially increased risk of CVD in woman exposed to PE. PMID:25712723

  18. Inflammatory and vascular placental lesions are associated with neonatal amplitude integrated EEG recording in early premature neonates.

    Directory of Open Access Journals (Sweden)

    Dorit Paz-Levy

    Full Text Available Placental histologic examination can assist in revealing the mechanism leading to preterm birth. Accumulating evidence suggests an association between intrauterine pathological processes, morbidity and mortality of premature infants, and their long term outcome. Neonatal brain activity is increasingly monitored in neonatal intensive care units by amplitude integrated EEG (aEEG and indices of background activity and sleep cycling patterns were correlated with long term outcome. We hypothesized an association between types of placental lesions and abnormal neonatal aEEG patterns.To determine the association between the placental lesions observed in extreme preterm deliveries, and their neonatal aEEG patterns and survival.This prospective cohort study included extreme premature infants, who were born ≤ 28 weeks of gestation, their placentas were available for histologic examination, and had a continues aEEG, soon after birthn = 34. Infants and maternal clinical data were collected. aEEG data was assessed for percentage of depressed daily activity in the first 3 days of life and for sleep cycling. Associations of placental histology with clinical findings and aEEG activity were explored using parametric and non-parametric statistics.Twenty two out of the 34 newborns survived to discharge. Preterm prelabor rupture of membranes (PPROM or chorioamnionitis were associated with placental lesions consistent with fetal amniotic fluid infection (AFI or maternal under perfusion (MUP (P < 0.05. Lesions consistent with fetal response to AFI were associated with absence of SWC pattern during the 1st day of life. Fetal-vascular-thrombo-occlusive lesions of inflammatory type were negatively associated with depressed cerebral activity during the 1st day of life, and with aEEG cycling during the 2nd day of life (P<0.05. Placental lesions associated with MUP were associated with depressed neonatal cerebral activity during the first 3 days of life (P = 0

  19. Pulmonary vascular responses during acute and sustained respiratory alkalosis or acidosis in intact newborn piglets.

    Science.gov (United States)

    Gordon, J B; Rehorst-Paea, L A; Hoffman, G M; Nelin, L D

    1999-12-01

    Acute alkalosis-induced pulmonary vasodilation and acidosis-induced pulmonary vasoconstriction have been well described, but responses were generally measured within 5-30 min of changing pH. In contrast, several in vitro studies have found that relatively brief periods of sustained alkalosis can enhance, and sustained acidosis can decrease, vascular reactivity. In this study of intact newborn piglets, effects of acute (20 min) and sustained (60-80 min) alkalosis or acidosis on baseline (35% O2) and hypoxic (12% O2) pulmonary vascular resistance (PVR) were compared with control piglets exposed only to eucapnia. Acute alkalosis decreased hypoxic PVR, but sustained alkalosis failed to attenuate either baseline PVR or the subsequent hypoxic response. Acute acidosis did not significantly increase hypoxic PVR, but sustained acidosis markedly increased both baseline PVR and the subsequent hypoxic response. Baseline PVR was similar in all piglets after resumption of eucapnic ventilation, but the final hypoxic response was greater in piglets previously exposed to alkalosis than in controls. Thus, hypoxic pulmonary vasoconstriction was not attenuated during sustained alkalosis, but was accentuated during sustained acidosis and after the resumption of eucapnia in alkalosis-treated piglets. Although extrapolation of data from normal piglets to infants and children with pulmonary hypertension must be done with caution, this study suggests that sustained alkalosis may be of limited efficacy in treating acute hypoxia-induced pulmonary hypertension and the risks of pulmonary hypertension must be considered when using ventilator strategies resulting in permissive hypercapnic acidosis.

  20. Augmentation of radiation response with the vascular targeting agent ZD6126

    International Nuclear Information System (INIS)

    Hoang Tien; Huang Shyhmin; Armstrong, Eric; Eickhoff, Jens C.; Harari, Paul M.

    2006-01-01

    Purpose: To examine the antivascular and antitumor activity of the vascular targeting agent ZD6126 in combination with radiation in lung and head-and-neck (H and N) cancer models. The overall hypothesis was that simultaneous targeting of tumor cells (radiation) and tumor vasculature (ZD6126) might enhance tumor cell killing. Methods and Materials: A series of in vitro studies using human umbilical vein endothelial cells (HUVEC) and in vivo studies in athymic mice bearing human lung (H226) and H and N (squamous cell carcinoma [SCC]1, SCC6) tumor xenografts treated with ZD6126 and/or radiation were performed. Results: ZD6126 inhibited the capillary-like network formation in HUVEC. Treatment of HUVEC with ZD6126 resulted in cell cycle arrest in G2/M, with decrease of cells in S phase and proliferation inhibition in a dose-dependent manner. ZD6126 augmented the cell-killing effect of radiation and radiation-induced apoptosis in HUVEC. The combination of ZD6126 and radiation further decreased tumor vascularization in an in vivo Matrigel angiogenesis assay. In tumor xenografts, ZD6126 enhanced the antitumor activity of radiation, resulting in tumor growth delay. Conclusions: These preclinical studies suggest that ZD6126 can augment the radiation response of proliferating endothelial H and N and lung cancer cells. These results complement recent reports suggesting the potential value of combining radiation with vascular targeting/antiangiogenic agents

  1. Identification of chemical components of combustion emissions that affect pro-atherosclerotic vascular responses in mice.

    Science.gov (United States)

    Seilkop, Steven K; Campen, Matthew J; Lund, Amie K; McDonald, Jacob D; Mauderly, Joe L

    2012-04-01

    Combustion emissions cause pro-atherosclerotic responses in apolipoprotein E-deficient (ApoE/⁻) mice, but the causal components of these complex mixtures are unresolved. In studies previously reported, ApoE⁻/⁻ mice were exposed by inhalation 6 h/day for 50 consecutive days to multiple dilutions of diesel or gasoline exhaust, wood smoke, or simulated "downwind" coal emissions. In this study, the analysis of the combined four-study database using the Multiple Additive Regression Trees (MART) data mining approach to determine putative causal exposure components regardless of combustion source is reported. Over 700 physical-chemical components were grouped into 45 predictor variables. Response variables measured in aorta included endothelin-1, vascular endothelin growth factor, three matrix metalloproteinases (3, 7, 9), metalloproteinase inhibitor 2, heme-oxygenase-1, and thiobarbituric acid reactive substances. Two or three predictors typically explained most of the variation in response among the experimental groups. Overall, sulfur dioxide, ammonia, nitrogen oxides, and carbon monoxide were most highly predictive of responses, although their rankings differed among the responses. Consistent with the earlier finding that filtration of particles had little effect on responses, particulate components ranked third to seventh in predictive importance for the eight response variables. MART proved useful for identifying putative causal components, although the small number of pollution mixtures (4) can provide only suggestive evidence of causality. The potential independent causal contributions of these gases to the vascular responses, as well as possible interactions among them and other components of complex pollutant mixtures, warrant further evaluation.

  2. Contact area affects frequency-dependent responses to vibration in the peripheral vascular and sensorineural systems.

    Science.gov (United States)

    Krajnak, Kristine; Miller, G R; Waugh, Stacey

    2018-01-01

    Repetitive exposure to hand-transmitted vibration is associated with development of peripheral vascular and sensorineural dysfunctions. These disorders and symptoms associated with it are referred to as hand-arm vibration syndrome (HAVS). Although the symptoms of the disorder have been well characterized, the etiology and contribution of various exposure factors to development of the dysfunctions are not well understood. Previous studies performed using a rat-tail model of vibration demonstrated that vascular and peripheral nervous system adverse effects of vibration are frequency-dependent, with vibration frequencies at or near the resonant frequency producing the most severe injury. However, in these investigations, the amplitude of the exposed tissue was greater than amplitude typically noted in human fingers. To determine how contact with vibrating source and amplitude of the biodynamic response of the tissue affects the risk of injury occurring, this study compared the influence of frequency using different levels of restraint to assess how maintaining contact of the tail with vibrating source affects the transmission of vibration. Data demonstrated that for the most part, increasing the contact of the tail with the platform by restraining it with additional straps resulted in an enhancement in transmission of vibration signal and elevation in factors associated with vascular and peripheral nerve injury. In addition, there were also frequency-dependent effects, with exposure at 250 Hz generating greater effects than vibration at 62.5 Hz. These observations are consistent with studies in humans demonstrating that greater contact and exposure to frequencies near the resonant frequency pose the highest risk for generating peripheral vascular and sensorineural dysfunction.

  3. Nitric oxide and TNFα are critical regulators of reversible lymph node vascular remodeling and adaptive immune response.

    Directory of Open Access Journals (Sweden)

    Stephanie L Sellers

    Full Text Available Lymph node (LN vascular growth, at the level of the main arteriole, was recently characterized for the first time during infection. Arteriole diameter was shown to increase for at least seven days and to occur via a CD4(+ T cell dependent mechanism, with vascular expansion playing a critical role in regulating induction of adaptive immune response. Here, using intravital microscopy of the inguinal LN during herpes simplex type II (HSV-2 infection, the data provides the first studies that demonstrate arteriole expansion during infection is a reversible vascular event that occurs via eutrophic outward remodeling. Furthermore, using genetic ablation models, and pharmacological blockade, we reveal arteriole remodeling and LN hypertrophy to be dependent upon both endothelial nitric oxide synthase (eNOS and TNFα expression. Additionally, we reveal transient changes in nitric oxide (NO levels to be a notable feature of response to viral infection and LN vascular remodeling and provide evidence that mast cells are the critical source of TNFα required to drive arteriole remodeling. Overall, this study is the first to fully characterize LN arteriole vascular changes throughout the course of infection. It effectively reveals a novel role for NO and TNFα in LN cellularity and changes in LN vascularity, which represent key advances in understanding LN vascular physiology and adaptive immune response.

  4. Leg vascular and skeletal muscle mitochondrial adaptations to aerobic high-intensity exercise training are enhanced in the early postmenopausal phase

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin; Egelund, Jon; Mandrup Jensen, Camilla Maria

    2017-01-01

    the haemodynamic response to acute exercise in matched pre- and postmenopausal women before and after 12 weeks of aerobic high intensity exercise training. Twenty premenopausal and 16 early postmenopausal (3.1 ± 0.5 [mean ± SEM] years after final menstrual period) women only separated by 4 (50 ± 0 versus 54 ± 1...... receptor α (ERRα) were increased (P training in the postmenopausal women whereas only the levels of mitochondrial complex V, eNOS, and COX-2 were increased (P aerobic......Exercise training leads to favourable adaptations within skeletal muscle; however, this effect of exercise training may be blunted in postmenopausal women due to the loss of oestrogens. Furthermore, postmenopausal women may have an impaired vascular response to acute exercise. We examined...

  5. Vascular smooth muscle responsiveness to nitric oxide is reduced in healthy adults with increased adiposity

    OpenAIRE

    Christou, Demetra D.; Pierce, Gary L.; Walker, Ashley E.; Hwang, Moon-Hyon; Yoo, Jeung-Ki; Luttrell, Meredith; Meade, Thomas H.; English, Mark; Seals, Douglas R.

    2012-01-01

    Vascular smooth muscle responsiveness to nitric oxide, as assessed by nitroglycerin-induced dilation (NID), is impaired in clinical cardiovascular disease, but its relation to adiposity is unknown. We determined the relation of NID to total and abdominal adiposity in healthy adults varying widely in adiposity. In 224 men and women [age, 18–79 years; body mass index (BMI), 16.4–42.2 kg/m2], we measured NID (brachial artery dilation to 0.4 mg sublingual nitroglycerin), total body adiposity [BMI...

  6. Mobilization of endothelial precursor cells: systemic vascular response to musculoskeletal trauma.

    LENUS (Irish Health Repository)

    Laing, A J

    2012-02-03

    Postnatal vasculogenesis, the process by which vascular committed bone marrow stem cells or endothelial precursor cells (EPC) migrate, differentiate, and incorporate into the nacent endothelium contributing to physiological and pathological neovascularization, has stimulated much interest. Its contribution to tumor nonvascularization, wound healing, and revascularization associated with skeletal and cardiac muscles ischaemia is established. We evaluated the mobilization of EPCs in response to musculoskeletal trauma. Blood from patients (n = 15) following AO type 42a1 closed diaphyseal tibial fractures was analyzed for CD34 and AC133 cell surface marker expression. Immunomagnetically enriched CD34+ mononuclear cell (MNC(CD34+)) populations were cultured and examined for phenotypic and functional vascular endothelial differentiation. Circulating MNC(CD34+) levels increased sevenfold by day 3 postinjury. Circulating MNC(AC133+) increased 2.5-fold. Enriched MNC(CD34+) populations from day 3 samples in culture exhibited cell cluster formation with sprouting spindles. These cells bound UEA-1 and incorporated fluorescent DiI-Ac-LDL intracellularily. Our findings suggest a systemic provascular response is initiated in response to musculoskeletal trauma. Its therapeutic manipulation may have implications for the potential enhancement of fracture healing.

  7. Repetitive muscle compression reduces vascular mechano-sensitivity and the hyperemic response to muscle contraction.

    Science.gov (United States)

    Messere, A; Turturici, M; Millo, G; Roatta, S

    2017-06-01

    Animal studies have shown that the rapid hyperemic response to external muscle compression undergoes inactivation upon repetitive stimulation, but this phenomenon has never been observed in humans. The aim of the present study was to determine whether 1) the vascular mechano-sensitivity underlying muscle compression-induced hyperemia is inactivated in an inter-stimulus interval (ISI)-dependent fashion upon repetitive stimulation, as suggested by animal studies, and 2) whether such inactivation also attenuates contraction-induced hyperemia. Brachial artery blood flow was measured by echo Doppler sonography in 13 healthy adults in response to 1) single and repetitive cuff muscle compression (CMC) of the forearm (20 CMCs, 1 s ISI); 2) a sequence of CMC delivered at decreasing ISI from 120 to 2 s; and 3) electrically-stimulated contraction of the forearm muscles before and after repetitive CMC. The peak amplitude of hyperemia in response to CMC normalized to baseline decreased from 2.2 ± 0.6 to 1.4 ± 0.4 after repetitive CMC and, in general, was decreased at ISI < 240 s. The peak amplitude of contraction-induced hyperemia was attenuated after as compared to before repeated CMC (1.7 ± 0.4 and 2.6 ± 0.6, respectively). Mechano-sensitivity of the vascular network can be conditioned by previous mechanical stimulation, and such preconditioning may substantially decrease contraction-induced hyperemia.

  8. Effects of whole-body cryotherapy duration on thermal and cardio-vascular response.

    Science.gov (United States)

    Fonda, Borut; De Nardi, Massimo; Sarabon, Nejc

    2014-05-01

    Whole-body cryotherapy (WBC) is the exposure of minimally dressed participants to very cold air, either in a specially designed chamber (cryo-chamber) or cabin (cryo-cabin), for a short period of time. Practitioners are vague when it comes to recommendations on the duration of a single session. Recommended exposure for cryo-chamber is 150s, but no empirically based recommendations are available for a cryo-cabin. Therefore the aim of this study was to examine thermal and cardio-vascular responses after 90, 120, 150 and 180s of WBC in a cryo-cabin. Our hypothesis was that skin temperature would be significantly lower after longer exposers. Twelve male participants (age 23.9±4.2 years) completed four WBC of different durations (90, 120, 150 and 180s) in a cryo-cabin. Thermal response, heart rate and blood pressure were measured prior, immediately after, 5min after and 30min after the session. Skin temperature differed significantly among different durations, except between 150 and 180s. There was no significant difference in heart rate and blood pressure. Thermal discomfort during a single session displayed a linear increase throughout the whole session. Our results indicate that practitioners and clinicians using cryo-cabin for WBC do not need to perform sessions longer than 150s. We have shown that longer sessions do not substantially affect thermal and cardio-vascular response, but do increase thermal discomfort. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Enhanced adhesion of early endothelial progenitor cells to radiation-induced senescence-like vascular endothelial cells in vitro

    International Nuclear Information System (INIS)

    Sermsathanasawadi, N.; Inoue, Yoshinori; Iwai, Takehisa; Ishii, Hideto; Yoshida, Masayuki; Igarashi, Kaori; Miura, Masahiko

    2009-01-01

    The effects of ionizing radiation (IR) on tumor neovascularization are still unclear. We previously reported that vascular endothelial cells (ECs) expressing the IR-induced senescence-like (IRSL) phenotype exhibit a significant decrease in angiogenic activity in vitro. In this study, we examined the effects of the IRSL phenotype on adhesion to early endothelial progenitor cells (early EPCs). Adhesion of human peripheral blood-derived early EPCs to human umbilical vein endothelial cells (HUVECs) expressing the IRSL phenotype was evaluated by an adhesion assay under static conditions. It was revealed that the IRSL HUVECs supported significantly more adhesion of early EPCs than normal HUVECs. Expressions of ICAM-1, VCAM-1 and E-selectin were up-regulated in IRSL HUVECs. Pre-treatment of IRSL HUVECs with adhesion-blocking monoclonal antibodies against E-selectin and VCAM-1 significantly reduced early EPC adhesion to IRSL HUVECs, suggesting a potential role for the E-selectin and VCAM-1 in the adhesion between IRSL ECs and early EPCs. Therefore, the IRSL phenotype expressed in ECs may enhance neovascularization via increased homing of early EPCs. Our findings are first to implicate the complex effects of this phenotype on tumor neovascularization following irradiation. (author)

  10. Carbon nanotubes as VEGF carriers to improve the early vascularization of porcine small intestinal submucosa in abdominal wall defect repair

    Directory of Open Access Journals (Sweden)

    Liu Z

    2014-03-01

    Full Text Available Zhengni Liu,1,* Xueyi Feng,2,* Huichun Wang,1 Jun Ma,1 Wei Liu,3 Daxiang Cui,4 Yan Gu,1 Rui Tang,11Department of General Surgery, Shanghai Ninth People’s Hospital, Hernia and Abdominal Wall Disease Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of General Surgery, Lu’an People’s Hospital, Lu’an Affiliated Hospital of Anhui Medical University, Lu’an, Province Anhui, People’s Republic of China; 3Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, Shanghai, People’s Republic of China; 4Institute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Microfabrication Technology of the Ministry of Education, Research Institute of Micro/Nano Science and Technology, Bio-X Center, Shanghai Jiao Tong University, Shanghai, People's Republic of China *These authors contributed equally to this work Abstract: Insufficient early vascularization in biological meshes, resulting in limited host tissue incorporation, is thought to be the primary cause for the failure of abdominal wall defect repair after implantation. The sustained release of exogenous angiogenic factors from a biocompatible nanomaterial might be a way to overcome this limitation. In the study reported here, multiwalled carbon nanotubes (MWNT were functionalized by plasma polymerization to deliver vascular endothelial growth factor165 (VEGF165. The novel VEGF165-controlled released system was incorporated into porcine small intestinal submucosa (PSIS to construct a composite scaffold. Scaffolds incorporating varying amounts of VEGF165-loaded functionalized MWNT were characterized in vitro. At 5 weight percent MWNT, the scaffolds exhibited optimal properties and were implanted in rats to repair abdominal wall defects. PSIS scaffolds incorporating VEGF165-loaded MWNT (VEGF

  11. Possible relationships between the early inflammatory response and subsequent fibrosis in rat skin after irradiation

    International Nuclear Information System (INIS)

    Ullrich, R.L.

    1975-01-01

    This study was designed to examine possible mechanistic relationships between the early inflammatory response and the subsequent fibrosis seen after radiation exposure. Anesthetized Rochester ex-Wistar rats were given single x-ray doses of either 2000 or 5000 rads to standardized fields of the inner thigh. The data suggest that two mechanisms are responsible for the radiation-induced increase in extravasation rate and vascular injury seen early after irradiation. First, direct cytocidal damage of the endothelium; and second, chemically mediated, possibly complement dependent mechanisms. Indirect histological evidence suggests a correlation between the PMN infiltrate and the indirect vascular damage. In addition, one may conclude from these data that (1) both direct and indirect damage to the vasculature play a role in influencing the subsequent late radiation-induced fibrosis; and (2) a decrease in the indirect damage may allow the maintenance of a supportive vasculature at lower doses or allow the reestablishment of a vascular bed in the case of higher doses

  12. Gastric antral vascular ectasia and its clinical correlates in patients with early diffuse systemic sclerosis in the SCOT trial.

    Science.gov (United States)

    Hung, Emily W; Mayes, Maureen D; Sharif, Roozbeh; Assassi, Shervin; Machicao, Victor I; Hosing, Chitra; St Clair, E William; Furst, Daniel E; Khanna, Dinesh; Forman, Stephen; Mineishi, Shin; Phillips, Kristine; Seibold, James R; Bredeson, Christopher; Csuka, Mary Ellen; Nash, Richard A; Wener, Mark H; Simms, Robert; Ballen, Karen; Leclercq, Sharon; Storek, Jan; Goldmuntz, Ellen; Welch, Beverly; Keyes-Elstein, Lynette; Castina, Sharon; Crofford, Leslie J; Mcsweeney, Peter; Sullivan, Keith M

    2013-04-01

    To describe the prevalence and clinical correlates of endoscopic gastric antral vascular ectasia (GAVE; "watermelon stomach") in early diffuse systemic sclerosis (SSc). Subjects with early, diffuse SSc and evidence of specific internal organ involvement were considered for the Scleroderma: Cyclophosphamide Or Transplant (SCOT) trial. In the screening procedures, all patients underwent upper gastrointestinal endoscopy. Patients were then categorized into those with or without endoscopic evidence of GAVE. Demographic data, clinical disease characteristics, and autoantibody data were compared using Pearson chi-square or Student t tests. Twenty-three of 103 (22.3%) individuals were found to have GAVE on endoscopy. Although not statistically significant, anti-topoisomerase I (anti-Scl70) was detected less frequently among those with GAVE (18.8% vs 44.7%; p = 0.071). Similarly, anti-RNP antibodies (anti-U1 RNP) showed a trend to a negative association with GAVE (0 vs 18.4%; p = 0.066). There was no association between anti-RNA polymerase III and GAVE. Patients with GAVE had significantly more erythema or vascular ectasias in other parts of the stomach (26.1% vs 5.0%; p = 0.003). Endoscopic GAVE was present on screening in almost one-fourth of these highly selected patients with early and severe diffuse SSc. While anti-Scl70 and anti-U1 RNP trended toward a negative association with GAVE, there was no correlation between anti-RNA Pol III and GAVE. Patients with GAVE had a higher frequency of other gastric vascular ectasias outside the antrum, suggesting that GAVE may represent part of the spectrum of the vasculopathy in SSc.

  13. Adipose derived stromal vascular fraction improves early tendon healing: an experimental study in rabbits

    Directory of Open Access Journals (Sweden)

    Mehdi Behfar

    2011-11-01

    Full Text Available Tendon never restores the complete biological and mechanical properties after healing. Bone marrow and recently adipose tissue have been used as the sources of mesenchymal stem cells, which have been proven to enhance tendon healing. Stromal vascular fraction (SVF, derived from adipose tissue by an enzymatic digestion, represents an alternative source of multipotent cells, which undergo differentiation into multiple lineages to be used in regenerative medicine. In the present study, we investigated potentials of this source on tendon healing. Twenty rabbits were divided into control and treatment groups. Five rabbits were used as donors of adipose tissue. The injury model was unilateral complete transection through the middle one third of deep digital flexor tendon. Immediately after suture repair, either fresh stromal vascular fraction from enzymatic digestion of adipose tissue or placebo was intratendinously injected into the suture site in treatments and controls, respectively. Cast immobilization was continued for two weeks after surgery. Animals were sacrificed at the third week and tendons underwent histological, immunohistochemical, and mechanical evaluations. By histology, improved fibrillar organization and remodeling of neotendon were observed in treatment group. Immunohistochemistry revealed an insignificant increase in collagen type III and I expression in treatments over controls. Mechanical testing showed significant increase in maximum load and energy absorption in SVF treated tendons. The present study showed that intratendinous injection of uncultured adipose derived stromal vascular fraction improved structural and mechanical properties of repaired tendon and it could be an effective modality for treating tendon laceration.

  14. Increased vascularization during early healing after biologic augmentation in repair of chronic rotator cuff tears using autologous leukocyte- and platelet-rich fibrin (L-PRF): a prospective randomized controlled pilot trial.

    Science.gov (United States)

    Zumstein, Matthias A; Rumian, Adam; Lesbats, Virginie; Schaer, Michael; Boileau, Pascal

    2014-01-01

    We hypothesized that arthroscopic rotator cuff repairs using leukocyte- and platelet-rich fibrin (L-PRF) in a standardized, modified protocol is technically feasible and results in a higher vascularization response and watertight healing rate during early healing. Twenty patients with chronic rotator cuff tears were randomly assigned to 2 treatment groups. In the test group (N = 10), L-PRF was added in between the tendon and the bone during arthroscopic rotator cuff repair. The second group served as control (N = 10). They received the same arthroscopic treatment without the use of L-PRF. We used a double-row tension band technique. Clinical examinations including subjective shoulder value, visual analog scale, Constant, and Simple Shoulder Test scores and measurement of the vascularization with power Doppler ultrasonography were made at 6 and 12 weeks. There have been no postoperative complications. At 6 and 12 weeks, there was no significant difference in the clinical scores between the test and the control groups. The mean vascularization index of the surgical tendon-to-bone insertions was always significantly higher in the L-PRF group than in the contralateral healthy shoulders at 6 and 12 weeks (P = .0001). Whereas the L-PRF group showed a higher vascularization compared with the control group at 6 weeks (P = .001), there was no difference after 12 weeks of follow-up (P = .889). Watertight healing was obtained in 89% of the repaired cuffs. Arthroscopic rotator cuff repair with the application of L-PRF is technically feasible and yields higher early vascularization. Increased vascularization may potentially predispose to an increased and earlier cellular response and an increased healing rate. Copyright © 2014 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

  15. Rate dependency and role of nitric oxide in the vascular response to direct cooling in human skin.

    Science.gov (United States)

    Yamazaki, Fumio; Sone, Ryoko; Zhao, Kun; Alvarez, Guy E; Kosiba, Wojciech A; Johnson, John M

    2006-01-01

    Local cooling of nonglabrous skin without functional sympathetic nerves causes an initial vasodilation followed by vasoconstriction. To further characterize these responses to local cooling, we examined the importance of the rate of local cooling and the effect of nitric oxide synthase (NOS) inhibition in intact skin and in skin with vasoconstrictor function inhibited. Release of norepinephrine was blocked locally (iontophoresis) with bretylium tosylate (BT). Skin blood flow was monitored from the forearm by laser-Doppler flowmetry (LDF). Cutaneous vascular conductance (CVC) was calculated as the ratio of LDF to blood pressure. Local temperature was controlled over 6.3 cm2 around the sites of LDF measurement. Local cooling was applied at -0.33 or -4 degrees C/min. At -4 degrees C/min, CVC increased (P cooling (-4 degrees C/min) to 24 degrees C decreased (P cooling, CVC decreased at BT + saline sites relative to the precooling levels (P cooling, but not functional NOS, is an important determinant of the early non-adrenergic vasodilator response to local cooling and that functional NOS, adrenergic nerves, as well as other mechanisms play roles in vasoconstriction during prolonged local cooling of skin.

  16. Vegetative and hemodynamic responses to stress in adolescents with constitutional-exogenous obesity and vascular dystonia of hypertensive type

    OpenAIRE

    Larina, N.

    2011-01-01

    We studied the characteristics of central hemodynamics and autonomic responses to cold and psycho-emotional test in adolescents with obesity and vascular dystonia of hypertensive type. Various options for the autonomic responses accompanied by changes in central hemodynamics as a function of body weight have been identified.

  17. MicroRNA-125b Affects Vascular Smooth Muscle Cell Function by Targeting Serum Response Factor

    Directory of Open Access Journals (Sweden)

    Zhibo Chen

    2018-04-01

    Full Text Available Background/Aims: Increasing evidence links microRNAs to the pathogenesis of peripheral vascular disease. We recently found microRNA-125b (miR-125b to be one of the most significantly down‑regulated microRNAs in human arteries with arteriosclerosis obliterans (ASO of the lower extremities. However, its function in the process of ASO remains unclear. This study aimed to investigate the expression, regulatory mechanisms, and functions of miR-125b in the process of ASO. Methods: Using the tissue explants adherent method, vascular smooth muscle cells (VSMCs were prepared for this study. A rat carotid artery balloon injury model was constructed to simulate the development of vascular neointima, and a lentiviral transduction system was used to overexpress serum response factor (SRF or miR-125b. Quantitative real‑time PCR (qRT‑PCR was used to detect the expression levels of miR‑125b and SRF mRNA. Western blotting was performed to determine the expression levels of SRF and Ki67. In situ hybridization analysis was used to analyze the location and expression levels of miR-125b. CCK-8 and EdU assays were used to assess cell proliferation, and transwell and wound closure assays were performed to measure cell migration. Flow cytometry was used to evaluate cell apoptosis, and a dual-luciferase reporter assay was conducted to examine the effects of miR‑125b on SRF. Immunohistochemistry and immunofluorescence analyses were performed to analyze the location and expression levels of SRF and Ki67. Results: miR-125b expression was decreased in ASO arteries and platelet-derived growth factor (PDGF-BB-stimulated VSMCs. miR-125b suppressed VSMC proliferation and migration but promoted VSMC apoptosis. SRF was determined to be a direct target of miR-125b. Exogenous miR-125b expression modulated SRF expression and inhibited vascular neointimal formation in balloon-injured rat carotid arteries. Conclusions: These findings demonstrate a specific role of the mi

  18. PP064. Total vascular resistances in early pregnancy: A key to understand abnormal cardiovascular adaptation associated with spontaneous abortion.

    Science.gov (United States)

    Lo Presti, Damiano; Scala, Roberta Licia; Tiralongo, Grazia Maria; Pisani, Ilaria; Gagliardi, Giulia; Novelli, Gian Paolo; Vasapollo, Barbara; Valensise, Herbert

    2013-04-01

    From early pregnancy, maternal hemodynamic profile begins to change. The absence of these changes leads to increased risk of complication during the gestation. Aim of this study is to understand in early pregnancy the behaviour of total vascular resistances (TVR) as a sign of maternal cardiovascular adaptation to pregnancy. A cross section study was conducted. We followed 160 healthy women with singleton pregnancy during the first trimester of gestation. We evaluated cardiac output (CO) and TVR at 7, 9 and 11 weeks of gestation. We obtained the following haemodynamic measurements with the USCOM system, a non invasive method: heart rate (HR), systolic and diastolic blood pressure (SBP, DBP), CO and TVR. 160 healthy pregnant women were selected, 8 patients, were excluded for a bad signal. Absolute values of the haemodynamic measures are shown in Fig. 1. 41 patients underwent spontaneous embryonic demise. This last group of patients showed in 54% (group A) TVR values within the normal limits (TVR1200) and CO values below the normal adaptation to pregnancy. Table 1 shows hemodynamic measures for the group A and group B; we found differences in term of CO, TVR and PAS between the two groups. Elevated TVR might indicate an abnormal vascular adaptation already in first weeks of pregnancy. Moreover, in women who undergo to abortion, elevated TVR could be use to distinguish genetic or environmental causes of miscarriage. Copyright © 2013. Published by Elsevier B.V.

  19. [Use of magnetic therapy for treatment of early symptoms of vascular-type vibration syndrome in forestry workers].

    Science.gov (United States)

    Karczewska, M

    1996-01-01

    The objective of the study was to evaluate the efficacy of the use of magnetic fields (ELF-MF) of therapeutic parameters in the treatment of early symptoms of vascular-type vibration syndrome in forestry workers. The study covered 96 forestry workers, and the control group was composed of 29 sawyers who underwent a simulated treatment. Each worker was granted sick leave and applied 20 procedures by employing an Aplhatron 4100 device under the ambulatory conditions. The outcome of the treatment was evaluated directly after the last procedure and 3 months later. A diversified positive influence on individual subjective and objective pathological changes in regard to both direct and late effects was observed. The abatement of subjective disorders right after termination of the treatment was observed in 67.7% and objective disorders in 57.3%. A long-term improvement (after 3 months) was found in a smaller proportion of persons as the abatement of subjective disorders was reported by 59.3% while objective disorders persisted in 43.7%. The results obtained prove that the application of variable magnetic fields (ELF-MF) of therapeutic parameters is useful in the prophylaxis and treatment of pathological changes during the period of prodromal symptoms and early pathological changes in vascular-type vibration syndrome induced by local magnetic vibrations.

  20. Validation of the Addenbrooke's cognitive examination for detecting early Alzheimer's disease and mild vascular dementia in a German population.

    Science.gov (United States)

    Alexopoulos, P; Greim, B; Nadler, K; Martens, U; Krecklow, B; Domes, G; Herpertz, S; Kurz, A

    2006-01-01

    We assessed the diagnostic accuracy of the German version of the Addenbrooke's Cognitive Examination (ACE) in identifying early Alzheimer's disease (AD) and mild vascular dementia (VaD) in comparison with the conventional Mini-Mental State Examination (MMSE). The study refers to 50 patients with mild dementia of AD, 26 patients with mild dementia of vascular etiology and to 54 cognitively normal subjects. The ACE and MMSE were validated against an expert diagnosis based on a comprehensive diagnostic workup. Statistical analysis was performed using the receiver operator characteristics method. The optimal cut-off score for the ACE for detecting dementia in patients with early AD was 85/86, which had a sensitivity of 93% and a specificity of 86%. The optimal cut-off for the ACE for the identification of dementia in patients with mild VaD was also 85/86 and it had a sensitivity of 93% and a specificity of 100%. The kappa values imply a substantial agreement between the diagnoses made by the ACE and the MMSE. The German version of the ACE is a short and practical but accurate test battery for the identification of AD and VaD, assessing a broad range of cognitive functions and providing a wide profile of cognitive functions/dysfunctions.

  1. Effectiveness of evaluating tumor vascularization using 3D power Doppler ultrasound with high-definition flow technology in the prediction of the response to neoadjuvant chemotherapy for T2 breast cancer: a preliminary report.

    Science.gov (United States)

    Shia, Wei-Chung; Chen, Dar-Ren; Huang, Yu-Len; Wu, Hwa-Koon; Kuo, Shou-Jen

    2015-10-07

    The aim of this study was to evaluate the effectiveness of advanced ultrasound (US) imaging of vascular flow and morphological features in the prediction of a pathologic complete response (pCR) and a partial response (PR) to neoadjuvant chemotherapy for T2 breast cancer.Twenty-nine consecutive patients with T2 breast cancer treated with six courses of anthracycline-based neoadjuvant chemotherapy were enrolled. Three-dimensional (3D) power Doppler US with high-definition flow (HDF) technology was used to investigate the blood flow in and morphological features of the tumors. Six vascularity quantization features, three morphological features, and two vascular direction features were selected and extracted from the US images. A support vector machine was used to evaluate the changes in vascularity after neoadjuvant chemotherapy, and pCR and PR were predicted on the basis of these changes.The most accurate prediction of pCR was achieved after the first chemotherapy cycle, with an accuracy of 93.1% and a specificity of 85.5%, while that of a PR was achieved after the second cycle, with an accuracy of 79.31% and a specificity of 72.22%.Vascularity data can be useful to predict the effects of neoadjuvant chemotherapy. Determination of changes in vascularity after neoadjuvant chemotherapy using 3D power Doppler US with HDF can generate accurate predictions of the patient response, facilitating early decision-making.

  2. Effectiveness of evaluating tumor vascularization using 3D power Doppler ultrasound with high-definition flow technology in the prediction of the response to neoadjuvant chemotherapy for T2 breast cancer: a preliminary report

    International Nuclear Information System (INIS)

    Shia, Wei-Chung; Chen, Dar-Ren; Huang, Yu-Len; Wu, Hwa-Koon; Kuo, Shou-Jen

    2015-01-01

    The aim of this study was to evaluate the effectiveness of advanced ultrasound (US) imaging of vascular flow and morphological features in the prediction of a pathologic complete response (pCR) and a partial response (PR) to neoadjuvant chemotherapy for T2 breast cancer.Twenty-nine consecutive patients with T2 breast cancer treated with six courses of anthracycline-based neoadjuvant chemotherapy were enrolled. Three-dimensional (3D) power Doppler US with high-definition flow (HDF) technology was used to investigate the blood flow in and morphological features of the tumors. Six vascularity quantization features, three morphological features, and two vascular direction features were selected and extracted from the US images. A support vector machine was used to evaluate the changes in vascularity after neoadjuvant chemotherapy, and pCR and PR were predicted on the basis of these changes.The most accurate prediction of pCR was achieved after the first chemotherapy cycle, with an accuracy of 93.1% and a specificity of 85.5%, while that of a PR was achieved after the second cycle, with an accuracy of 79.31% and a specificity of 72.22%.Vascularity data can be useful to predict the effects of neoadjuvant chemotherapy. Determination of changes in vascularity after neoadjuvant chemotherapy using 3D power Doppler US with HDF can generate accurate predictions of the patient response, facilitating early decision-making. (paper)

  3. Effectiveness of evaluating tumor vascularization using 3D power Doppler ultrasound with high-definition flow technology in the prediction of the response to neoadjuvant chemotherapy for T2 breast cancer: a preliminary report

    Science.gov (United States)

    Shia, Wei-Chung; Chen, Dar-Ren; Huang, Yu-Len; Wu, Hwa-Koon; Kuo, Shou-Jen

    2015-10-01

    The aim of this study was to evaluate the effectiveness of advanced ultrasound (US) imaging of vascular flow and morphological features in the prediction of a pathologic complete response (pCR) and a partial response (PR) to neoadjuvant chemotherapy for T2 breast cancer. Twenty-nine consecutive patients with T2 breast cancer treated with six courses of anthracycline-based neoadjuvant chemotherapy were enrolled. Three-dimensional (3D) power Doppler US with high-definition flow (HDF) technology was used to investigate the blood flow in and morphological features of the tumors. Six vascularity quantization features, three morphological features, and two vascular direction features were selected and extracted from the US images. A support vector machine was used to evaluate the changes in vascularity after neoadjuvant chemotherapy, and pCR and PR were predicted on the basis of these changes. The most accurate prediction of pCR was achieved after the first chemotherapy cycle, with an accuracy of 93.1% and a specificity of 85.5%, while that of a PR was achieved after the second cycle, with an accuracy of 79.31% and a specificity of 72.22%. Vascularity data can be useful to predict the effects of neoadjuvant chemotherapy. Determination of changes in vascularity after neoadjuvant chemotherapy using 3D power Doppler US with HDF can generate accurate predictions of the patient response, facilitating early decision-making.

  4. Angiogenesis for tumor vascular normalization of Endostar on hepatoma 22 tumor-bearing mice is involved in the immune response.

    Science.gov (United States)

    Xu, Qingyu; Gu, Junfei; Lv, You; Yuan, Jiarui; Yang, Nan; Chen, Juan; Wang, Chunfei; Hou, Xuefeng; Jia, Xiaobin; Feng, Liang; Yin, Guowen

    2018-03-01

    Tumor vascular normalization involved in immune response is beneficial to the chemotherapy of tumors. Recombinant human endostatin (Endostar), an angiogenesis inhibitor, has been demonstrated to be effective in hepatocellular cancer (HCC). However, its vascular normalization in HCC and the role of the immune response in angiogenesis were unclear. In the present study, effects of Endostar on tumor vascular normalization were evaluated in hepatoma 22 (H22) tumor-bearing mice. Endostar was able to inhibit the proliferation and infiltration of tumor cells and improve α-fetoprotein, tumor necrosis factor-α and cyclic adenosine 5'-phosphate levels in the serum of H22-bearing mice, as well as the protein expression levels of the immune factors interferon-γ and cluster of differentiation (CD)86 in liver tissue. Endostar also exhibited more marked downregulation of the levels of vascular endothelial growth factor, CD31, matrix metalloproteinase (MMP)-2, MMP-9 and interleukin-17 during day 3-9 treatment, resulting in short-term normalization of tumor blood vessels. The period of vascular normalization was 3-9 days. The results of the present study demonstrated that Endostar was able to induce the period of vascular normalization, contributing to a more efficacious means of HCC treatment combined with other chemotherapy, and this effect was associated with the immune response. It may be concluded that Endostar inhibited immunity-associated angiogenesis behaviors of vascular endothelial cells in response to HCC. The results of the present study provided more reasonable possibility for the combination therapy of Endostar for the treatment of HCC.

  5. Effect of healthy aging on renal vascular responses to local cooling and apnea.

    Science.gov (United States)

    Patel, Hardikkumar M; Mast, Jessica L; Sinoway, Lawrence I; Muller, Matthew D

    2013-07-01

    Sympathetically mediated renal vasoconstriction may contribute to the pathogenesis of hypertension in older adults, but empirical data in support of this concept are lacking. In 10 young (26 ± 1 yr) and 11 older (67 ± 2 yr) subjects, we quantified acute hemodynamic responses to three sympathoexcitatory stimuli: local cooling of the forehead, cold pressor test (CPT), and voluntary apnea. We hypothesized that all stimuli would increase mean arterial blood pressure (MAP) and renal vascular resistance index (RVRI) and that aging would augment these effects. Beat-by-beat MAP, heart rate (HR), and renal blood flow velocity (from Doppler) were measured in the supine posture, and changes from baseline were compared between groups. In response to 1°C forehead cooling, aging was associated with an augmented MAP (20 ± 3 vs. 6 ± 2 mmHg) and RVRI (35 ± 6 vs. 16 ± 9%) but not HR. In older adults, there was a positive correlation between the cold-induced pressor response and forehead pain (R = 0.726), but this effect was not observed in young subjects. The CPT raised RVRI in both young (56 ± 13%) and older (45 ± 8%) subjects, but this was not different between groups. Relative to baseline, end-expiratory apnea increased RVRI to a similar extent in both young (46 ± 14%) and older (41 ± 9%) subjects. During sympathetic activation, renal vasoconstriction occurred in both groups. Forehead cooling caused an augmented pressor response in older adults that was related to pain perception.

  6. An early validation of the Society for Vascular Surgery lower extremity threatened limb classification system.

    Science.gov (United States)

    Cull, David L; Manos, Ginger; Hartley, Michael C; Taylor, Spence M; Langan, Eugene M; Eidt, John F; Johnson, Brent L

    2014-12-01

    The Society for Vascular Surgery (SVS) recently established the Lower Extremity Threatened Limb Classification System, a staging system using Wound characteristic, Ischemia, and foot Infection (WIfI) to stratify the risk for limb amputation at 1 year. Although intuitive in nature, this new system has not been validated. The purpose of the following study was to determine whether the WIfI system is predictive of limb amputation and wound healing. Between 2007 and 2010, we prospectively obtained data related to wound characteristics, extent of infection, and degree of postrevascularization ischemia in 139 patients with foot wounds who presented for lower extremity revascularization (158 revascularization procedures). After adapting those data to the WIfI classifications, we analyzed the influence of wound characteristics, extent of infection, and degree of ischemia on time to wound healing; empirical Kaplan-Meier survival curves were compared with theoretical outcomes predicted by WIfI expert consensus opinion. Of the 158 foot wounds, 125 (79%) healed. The median time to wound healing was 2.7 months (range, 1-18 months). Factors associated with wound healing included presence of diabetes mellitus (P = .013), wound location (P = .049), wound size (P = .007), wound depth (P = .004), and degree of ischemia (P valid. Further validation of the WIfI classification system with multicenter data is justified. Copyright © 2014 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

  7. Early Experience with the Amplatzer Vascular Plug II for Occlusive Purposes in Arteriovenous Hemodialysis Access

    International Nuclear Information System (INIS)

    Powell, Steven; Narlawar, Ranjeet; Odetoyinbo, Tolulola; Littler, Peter; Oweis, Deyana; Sharma, Ajay; Bakran, Ali

    2010-01-01

    The Amplatzer Vascular Plug Type II (AVP II) has proven effective in the therapeutic embolization of various vascular lesions. It benefits from very rapid occlusion of the target lesion and can be deployed, retrieved, and redeployed if required. There is no literature available on use of the AVP II in the maintenance, closure, and management of complicated arteriovenous access in hemodialysis patients. In this series, we present our clinical experience with the use of the AVP II for embolization of problematic hemodialysis access. The AVP II is a self-expandable Nitinol wire-mesh device. Mounted on a delivery wire it has the capability to be deployed, recaptured, and redeployed. In total seven patients (four males: one diabetic, all nonsmokers), with ages ranging from 44 to 81 years (mean, 63 years), were treated between July 2008 and January 2009. One patient had not started dialysis. The remaining six patients had varied histories, with the time on hemodialysis ranging from 1 to 21 years. Retrospective review of clinical notes revealed patient demographics, type of access, device size, deployment site, and outcomes. Indications for embolization included steal syndrome (one patient), high-flow tributaries (two patients), and limb swelling (four patients). All patients had clinical and sonographical follow-up to 3 months. Surgical ligation had either failed, was considered a contraindication due to concerns regarding wound healing, or was considered difficult due to complex venous anatomy. Only one device was used in each patient, ranging from 6 to 16 mm in diameter. Immediate technical success was seen in 100%. All these patients were followed up clinically in the vascular access radiology clinic at 4 weeks and 3 months. Occlusion of the treated vessel and resolution of symptoms were reconfirmed in 100% of cases at 3 months. It was also noted whether patients were having successful dialysis, if required. There were no complications. Average procedural time was 19

  8. Deferoxamine improves coronary vascular responses to sympathetic stimulation in patients with type 1 diabetes mellitus

    Energy Technology Data Exchange (ETDEWEB)

    Hattori, Naoya; Bengel, Frank M.; Nekolla, Stephan G.; Drzezga, Alexander E.; Schwaiger, Markus [Nuklearmedizinische Klinik und Poliklinik, Klinikum Rechts der Isar, Technischen Universitaet Muenchen (Germany); Schnell, Oliver; Rihl, Julian; Standl, Eberhard [Diabetes Research Center, Schwabing City Hospital, Munich (Germany)

    2002-07-01

    Effects of oxygen-derived free radicals are suggested to be a potential pathogenic factor for endothelial dysfunction. In this study we sought to evaluate the effect of hydroxyl radicals on the human coronary vascular bed in type I diabetes mellitus using positron emission tomography (PET). Thirteen patients with type 1 diabetes underwent PET using nitrogen-13 ammonia at rest and during sympathetic stimulation with the cold pressor test (CPT). The rest-stress study protocol was repeated twice (on different days) using pre-stress infusion of either saline as placebo or deferoxamine, an iron chelator which inhibits generation of hydroxyl radicals. At rest, global MBF was higher in diabetics than in normal controls (78.1{+-}17.5 vs 63.2{+-}14.9 mg 100 g{sup -1} min{sup -1}, P<0.05) and myocardial vascular resistance (MVR) showed a trend towards lower values (patients, 1.28{+-}0.35; controls, 1.55{+-}0.32, P=NS). CPT increased MBF in all controls while 7/13 diabetics responded normally. CPT decreased MVR in 10/13 controls but in only 4/13 diabetics. There was no significant difference in the duration of diabetes, HbA1c, daily insulin dose, body mass index, or lipid profiles between patients with and patients without abnormal MBF or MVR responses. Pre-stress infusion of deferoxamine normalized MBF response in all six patients, and MVR response in six of the nine patients. Another group consisting of seven patients underwent a rest-rest protocol after infusion of deferoxamine and saline to investigate the effect of deferoxamine on resting MBF. Deferoxamine did not change the resting MBF (deferoxamine, 81{+-}17 ml 100 g{sup -1} min{sup -1}; saline, 75{+-}19 ml 100 g{sup -1} min{sup -1}, P=NS) or MVR (deferoxamine, 1.0{+-}0.5 mmHg ml{sup -1} 100 g{sup -1} min{sup -1}; saline, 1.2{+-}0.6 mmHg ml{sup -1} 100 g{sup -1} min{sup -1}, P=NS). In conclusion, inhibition of hydroxyl radical formation using deferoxamine significantly improved the responses of coronary

  9. Vascular Changes and Neurodegeneration in the Early Stages of Diabetic Retinopathy

    DEFF Research Database (Denmark)

    Jonsson, Karoline Boegeberg; Frydkjaer-Olsen, Ulrik; Grauslund, Jakob

    2016-01-01

    INTRODUCTION: Neurodegeneration is an early component of diabetic retinopathy (DR). It is unclear whether neurodegeneration is an independent factor or a consequence of damaged retinal vasculature. The aims of this study were to review the literature concerning neurodegeneration in diabetic...

  10. [Medical and socio-economic effects of early rehabilitation of patients with acute cerebral vascular accidents].

    Science.gov (United States)

    Popov, A V; Cherednichenko, T V; Lishnevskiĭ, S A; Khomenko, T V; Prigornitskaia, Ia I

    2012-01-01

    Acute ischemic brain injury (stroke, stroke), a leader among the causes of morbidity and mortality in the world. This pathology is one of the most pressing health and social problems that cause enormous economic damage to society, due to the high fatality rate, significant disability and social maladjustment of patients, which is based in most cases are the motor and cognitive impairment. Despite the fact that, currently established risk factors and pathophysiological basis of this disease, the availability of effective methods of diagnosing illness, still a practicing neurologist in some cases difficult to find adequate therapy that could effectively reach a well-established neurological deficit. Therefore the search for treatments that effectively reduce the health and social consequences of vascular damage to the brain, is one of the priority areas of neurology.

  11. Calcineurin /NFAT activation-dependence of leptin synthesis and vascular growth in response to mechanical stretch

    Directory of Open Access Journals (Sweden)

    Nadia Soudani

    2016-09-01

    Full Text Available Background and Aims- Hypertension and obesity are important risk factors of cardiovascular disease. They are both associated with high leptin levels and have been shown to promote vascular hypertrophy, through the RhoA/ROCK and ERK1/2 phosphorylation. Calcineurin/NFAT activation also induces vascular hypertrophy by upregulating various genes. This study aimed to decipher whether a crosstalk exists between the RhoA/ROCK pathway, Ca+2/calcineurin/NFAT pathway, and ERK1/2 phosphorylation in the process of mechanical stretch-induced vascular smooth muscle cell (VSMC hypertrophy and leptin synthesis. Methods and Results- Rat portal vein (RPV organ culture was used to investigate the effect of mechanical stretch and exogenous leptin (3.1 nM on VSMC hypertrophy and leptin synthesis. Results showed that stretching the RPV significantly upregulated leptin secretion, mRNA and protein expression, which were inhibited by the calcium channel blocker nifedipine (10 μM, the selective calcineurin inhibitor FK506 (1 nM and the ERK1/2 inhibitor PD98059 (1 μM. The transcription inhibitor actinomycin D (0.1M and the translation inhibitor cycloheximide (1 mM significantly decreased stretch-induced leptin protein expression. Mechanical stretch or leptin caused an increase in wet weight changes and protein synthesis, considered as hypertrophic markers, while they were inhibited by FK506 (0.1 nM; 1 nM. In addition, stretch or exogenous leptin significantly increased calcineurin activity and MCIP1 expression whereas leptin induced NFAT nuclear translocation in VSMCs. Moreover, in response to stretch or exogenous leptin, the Rho inhibitor C3 exoenzyme (30 ng/mL, the ROCK inhibitor Y-27632 (10 μM, and the actin depolymerization agents Latrunculin B (50 nM and cytochalasin D (1 μM reduced calcineurin activation and NFAT nuclear translocation. ERK1/2 phosphorylation was inhibited by FK506 and C3. Conclusions- Mechanical stretch-induced VSMC hypertrophy and leptin

  12. Association of Vascular Endothelial Growth Factor Expression with Tumor Angiogenesis and with Early Relapse in Primary Breast Cancer

    Science.gov (United States)

    Hoshina, Seigo; Takayanagi, Toshiaki; Tominaga, Takeshi

    1994-01-01

    Angiogenesis is an independent prognostic indicator in breast cancer. In this report, the relationship between expression of vascular endothclial growth factor (VEGF; a selective mitogen for endothelial cells) and the microvessel density was examined in 103 primary breast cancers. The expression of VEGF was evaluated by immunocytochemical staining using anti‐VEGF antibody. The microvessel density, which was determined by immunostaining for factor VIII antigen, in VEGF‐rich tumors was clearly higher than that in VEGF‐poor tumors (P<0.01). There was a good correlation between VEGF expression and the increment of microvessel density. Furthermore, postoperative survey demonstrated that the relapse‐free survival rate of VEGF‐rich tumors was significantly worse than that of VEGF‐poor tumors. It was suggested that the expression of VEGF is closely associated with the promotion of angiogenesis and with early relapse in primary breast cancer. PMID:7525523

  13. Response of local vascular volumes to lower body negative pressure stress

    Science.gov (United States)

    Wolthuis, R. A.; Leblanc, A.; Carpentier, W. A.; Bergman, S. A., Jr.

    1975-01-01

    The present study involved an intravenous injection of radioactive iodinated serum albumin, equilibration of this isotope within the vascular space, and the continuous measurement of isotope activity over selected anatomical areas before, during and following multiple human LBNP tests. Both rate and magnitude of vascular pooling were distinctly different within each of five selected lower body anatomical areas. In the upper body, all areas except the abdomen showed depletions from their resting vascular volumes during LBNP. The presence of uniquely different pooling patterns in the lower body, the apparent stability of abdominal vascular volumes, and a possible decrease in cerebral blood volume during LBNP represent the major findings of this study.

  14. Uterine and placenta characteristics during early vascular development in the pig from day 22 to 42 of gestation.

    Science.gov (United States)

    Wright, Elane C; Miles, Jeremy R; Lents, Clay A; Rempel, Lea A

    2016-01-01

    Insufficient placenta development is one of the primary causes of fetal death and reduced fetal growth after 35 days of gestation. Between day 22 and 42 the placenta consists of a central highly vascular placenta (HVP), adjacent to the fetus, a less vascular placenta (LVP), on either side of the fetus, and necrotic tips (NT). The objective of this study was to comprehensively evaluate uterine-placenta characteristics during early gestation in the gilt and determine time points and physiological changes. Gilts (n=25) were artificially inseminated at first detection of estrus (day 0) and 24h later, and harvested at 22, 27, 32, 37 or 42 days of gestation. Litter size, 12.1±3.4, was similar for all days of gestation. Fetal and placenta weight increased with day of gestation. The greatest increase in placenta weight occurred between 37 and 42 days of gestation. The LVP zones had no measurable fold formation until day 27. Necrotic tips became apparent after 27 days of gestation. Unoccupied areas of the uterus developed folds with changes in endometrial cell size and morphology from day 32 to 42 of gestation. Limited changes occurred in either fetal growth or placenta weight from day 27 through 32 of gestation; however, significant morphological changes occur at the maternal-fetal interface, demonstrating the dynamic architecture of the developing porcine placenta during early gestation. This work establishes fundamental time points in placenta development corresponding to fetal growth and microfold formation that may influence fetal growth and impact fetal survival. Published by Elsevier B.V.

  15. Forearm vascular response to nitric oxide and calcitonin gene-related peptide: comparison between migraine patients and control subjects.

    NARCIS (Netherlands)

    Hoon, J.N. de; Smits, P.; Troost, J.; Struijker-Boudier, H.A.; Bortel, L.M. van

    2006-01-01

    The forearm vascular response to nitric oxide (NO) and calcitonin gene-related peptide (CGRP) was investigated in 10 migraine patients and 10 matched control subjects. Changes in forearm blood flow (FBF) during intrabrachial infusion of: (i) serotonin (releasing endogenous NO), (ii) sodium

  16. Experimental study on the vascular thermal response to visible laser pulses.

    Science.gov (United States)

    Li, D; Chen, B; Wu, W J; Wang, G X; He, Y L; Ying, Z X

    2015-01-01

    Port-wine stains (PWSs) are congenital vascular malformations that progressively darken and thicken with age, and laser therapy is the most effective in clinical practice. Using dorsal skin chamber (DSC), this study evaluated thermal response of blood vessel to a 595-nm pulsed dye laser (PDL) with controlled energy doses and pulse durations. Totally, 32 vessels (30∼300 μm in diameter) are selected from the dorsal skin of the mouse to match those in port-wine stain. The experimental results showed that the thermal response of the blood vessels to laser irradiation can be recognized as coagulation, constriction with diameter decrease, disappearance (complete constriction), hemorrhage, and collagen damage in the order of increasing laser radiant exposure. Blood vessels with small diameter would response poorly and survive from the laser heating because their thermal relaxation time is much shorter than the pulse duration. The optimalradiant exposure is from 10 to 12 J/cm(2) under 6 ms pulse duration without considering the epidermal light absorption. Numerical simulations were also conducted using a 1,000-μm deep Sprague-Dawley (SD) mouse skinfold. The light transportation and heat diffusion in dorsal skin were simulated with the Monte Carlo method and heat transfer equation, while the blood vessel photocoagulation was evaluated by Arrhenius-type kinetic integral. Both experimental observation and numerical simulation supported that hemorrhage is the dominant thermal response, which occurs due to preferential heating of the superior parts of large blood vessels. In clinical practice for 595 nm PDL, the consequent purpura caused by hemorrhage can be used as a treatment end point.

  17. Metformin inhibits inflammatory response via AMPK–PTEN pathway in vascular smooth muscle cells

    International Nuclear Information System (INIS)

    Kim, Sun Ae; Choi, Hyoung Chul

    2012-01-01

    Highlights: ► PTEN was induced by metformin and inhibited by compound C and AMPK siRNA. ► Metformin suppressed TNF-α-induced COX-2 and iNOS mRNA expression. ► Compound C and bpv (pic) increased iNOS and COX-2 protein expression. ► NF-κB activation was restored by inhibiting AMPK and PTEN. ► AMPK and PTEN regulated TNF-α-induced ROS production in VSMCs. -- Abstract: Atherosclerosis is a chronic inflammation of the coronary arteries. Vascular smooth muscle cells (VSMCs) stimulated by cytokines and chemokines accelerate the inflammatory response and migrate to the injured endothelium during the progression of atherosclerosis. Activation of AMP activated protein kinase (AMPK), a key sensor maintaining metabolic homeostasis, suppresses the inflammatory response. However, how AMPK regulates the inflammatory response is poorly understood. To identify the mechanism of this response, we focused on phosphatase and tensin homolog (PTEN), which is a negative regulator of inflammation. We investigated that activation of AMPK-induced PTEN expression and suppression of the inflammatory response through the AMPK–PTEN pathway in VSMCs. We treated with the well-known AMPK activator metformin to induce PTEN expression. PTEN was induced by metformin (2 mM) and inhibited by compound C (10 μM) and AMPK siRNA. Tumor necrosis factor-alpha (TNF-α) was used to induce inflammation. The inflammatory response was confirmed by cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS) expression, and activation of nuclear factor (NF)-κB. Metformin suppressed COX-2 and iNOS mRNA and protein expression dose dependently. Treatment with compound C and bpv (pic) in the presence of metformin, iNOS and COX-2 protein expression increased. NF-κB activation decreased in response to metformin and was restored by inhibiting AMPK and PTEN. Inhibiting AMPK and PTEN restored ROS levels stimulated with TNF-α. Taken together, PTEN could be a possible downstream regulator of AMPK, and the

  18. Metformin inhibits inflammatory response via AMPK-PTEN pathway in vascular smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sun Ae [Department of Pharmacology, Aging-Associated Vascular Disease Research Center, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of); Choi, Hyoung Chul, E-mail: hcchoi@med.yu.ac.kr [Department of Pharmacology, Aging-Associated Vascular Disease Research Center, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of)

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer PTEN was induced by metformin and inhibited by compound C and AMPK siRNA. Black-Right-Pointing-Pointer Metformin suppressed TNF-{alpha}-induced COX-2 and iNOS mRNA expression. Black-Right-Pointing-Pointer Compound C and bpv (pic) increased iNOS and COX-2 protein expression. Black-Right-Pointing-Pointer NF-{kappa}B activation was restored by inhibiting AMPK and PTEN. Black-Right-Pointing-Pointer AMPK and PTEN regulated TNF-{alpha}-induced ROS production in VSMCs. -- Abstract: Atherosclerosis is a chronic inflammation of the coronary arteries. Vascular smooth muscle cells (VSMCs) stimulated by cytokines and chemokines accelerate the inflammatory response and migrate to the injured endothelium during the progression of atherosclerosis. Activation of AMP activated protein kinase (AMPK), a key sensor maintaining metabolic homeostasis, suppresses the inflammatory response. However, how AMPK regulates the inflammatory response is poorly understood. To identify the mechanism of this response, we focused on phosphatase and tensin homolog (PTEN), which is a negative regulator of inflammation. We investigated that activation of AMPK-induced PTEN expression and suppression of the inflammatory response through the AMPK-PTEN pathway in VSMCs. We treated with the well-known AMPK activator metformin to induce PTEN expression. PTEN was induced by metformin (2 mM) and inhibited by compound C (10 {mu}M) and AMPK siRNA. Tumor necrosis factor-alpha (TNF-{alpha}) was used to induce inflammation. The inflammatory response was confirmed by cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS) expression, and activation of nuclear factor (NF)-{kappa}B. Metformin suppressed COX-2 and iNOS mRNA and protein expression dose dependently. Treatment with compound C and bpv (pic) in the presence of metformin, iNOS and COX-2 protein expression increased. NF-{kappa}B activation decreased in response to metformin and was restored by inhibiting AMPK

  19. Decreased endometrial vascularity and receptivity in unexplained recurrent miscarriage patients during midluteal and early pregnancy phases

    Directory of Open Access Journals (Sweden)

    Shu-Yin Tan

    2015-10-01

    Conclusion: The 3D-power Doppler ultrasound is a more comprehensive and sensitive method for evaluating endometrial receptivity. Endometrial volume, VI, FI, and VFI in the midluteal phase, as well as VI in early pregnancy, can be considered as predictive factors for recurrent miscarriage.

  20. DEPTOR regulates vascular endothelial cell activation and proinflammatory and angiogenic responses.

    Science.gov (United States)

    Bruneau, Sarah; Nakayama, Hironao; Woda, Craig B; Flynn, Evelyn A; Briscoe, David M

    2013-09-05

    The maintenance of normal tissue homeostasis and the prevention of chronic inflammatory disease are dependent on the active process of inflammation resolution. In endothelial cells (ECs), proinflammation results from the activation of intracellular signaling responses and/or the inhibition of endogenous regulatory/pro-resolution signaling networks that, to date, are poorly defined. In this study, we find that DEP domain containing mTOR interacting protein (DEPTOR) is expressed in different microvascular ECs in vitro and in vivo, and using a small interfering RNA (siRNA) knockdown approach, we find that it regulates mammalian target of rapamycin complex 1 (mTORC1), extracellular signal-regulated kinase 1/2, and signal transducer and activator of transcription 1 activation in part through independent mechanisms. Moreover, using limited gene arrays, we observed that DEPTOR regulates EC activation including mRNA expression of the T-cell chemoattractant chemokines CXCL9, CXCL10, CXCL11, CX3CL1, CCL5, and CCL20 and the adhesion molecules intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 (P < .05). DEPTOR siRNA-transfected ECs also bound increased numbers of peripheral blood mononuclear cells (P < .005) and CD3+ T cells (P < .005) in adhesion assays in vitro and had increased migration and angiogenic responses in spheroid sprouting (P < .01) and wound healing (P < .01) assays. Collectively, these findings define DEPTOR as a critical upstream regulator of EC activation responses and suggest that it plays an important role in endogenous mechanisms of anti-inflammation and pro-resolution.

  1. Imaging vascular function for early stage clinical trials using dynamic contrast-enhanced magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Leach, M.O.; Orton, M. [Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Cancer Research UK and EPSRC Cancer Imaging Centre, Sutton, Surrey (United Kingdom); Morgan, B. [Univ. of Leicester, College of Medicine, Biological Sciences and Psychology, Leicester (United Kingdom); Tofts, P.S. [Brighton and Sussex Medical School, Univ. of Sussex, Clinical Imaging Sciences Centre, Sussex (United Kingdom); Buckley, D.L. [University of Leeds, Division of Medical Physics, Leeds (United Kingdom); Huang, W. [Oregon Health and Science Univ., Advanced Imaging Research Centre, Portland, OR (United States); Horsfield, M.A. [Medical Physics Section, Leicester Royal Infirmary, Dept. of Cardiovascular Sciences, Leicester (United Kingdom); Chenevert, T.L. [Univ. of Michigan Health System, Ann Arbor, MI (United States); Collins, D.J. [Royal Marsden Hospital NHS Foundation Trust, Cancer Research UK and EPSRC Cancer Imaging Centre, Sutton, Surrey (United Kingdom); Jackson, A. [Univ. of Manchester, Wolfson Molecular Imaging Centre, Withington, Manchester, M20 3LJ (United Kingdom); Lomas, D. [Univ. of Cambridge, Dept. of Radiology, Cambridge (United Kingdom); Whitcher, B. [Unit 2 Greenways Business Park, Mango Solutions, Chippenham (United Kingdom); Clarke, L. [Cancer Imaging Program, Imaging Technology Development Branch, Rockville, MD (United States); Plummer, R. [Univ. of Newcastle Upon Tyne, The Medical School, Medical Oncology, Northern Inst. for Cancer Research, Newcastle Upon Tyne (United Kingdom); Judson, I. [Royal Marsden Hospital, Sutton, Surrey (United Kingdom); Jones, R. [Beatson West of Scotland Cancer Centre, Glasgow (United Kingdom); Alonzi, R. [Mount Vernon Cancer Centre, Northwood (United Kingdom); Brunner, T. [Gray Inst. for Radiation, Oncology and Biology, Oxford (United Kingdom); Koh, D.M. [Royal Marsden NHS Foundation Trust, Diagnostic Radiology, Sutton, Surrey (United Kingdom)] [and others

    2012-07-15

    Many therapeutic approaches to cancer affect the tumour vasculature, either indirectly or as a direct target. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has become an important means of investigating this action, both pre-clinically and in early stage clinical trials. For such trials, it is essential that the measurement process (i.e. image acquisition and analysis) can be performed effectively and with consistency among contributing centres. As the technique continues to develop in order to provide potential improvements in sensitivity and physiological relevance, there is considerable scope for between-centre variation in techniques. A workshop was convened by the Imaging Committee of the Experimental Cancer Medicine Centres (ECMC) to review the current status of DCE-MRI and to provide recommendations on how the technique can best be used for early stage trials. This review and the consequent recommendations are summarised here. (orig.)

  2. Vascular disease in cocaine addiction.

    Science.gov (United States)

    Bachi, Keren; Mani, Venkatesh; Jeyachandran, Devi; Fayad, Zahi A; Goldstein, Rita Z; Alia-Klein, Nelly

    2017-07-01

    Cocaine, a powerful vasoconstrictor, induces immune responses including cytokine elevations. Chronic cocaine use is associated with functional brain impairments potentially mediated by vascular pathology. Although the Crack-Cocaine epidemic has declined, its vascular consequences are increasingly becoming evident among individuals with cocaine use disorder of that period, now aging. Paradoxically, during the period when prevention efforts could make a difference, this population receives psychosocial treatment at best. We review major postmortem and in vitro studies documenting cocaine-induced vascular toxicity. PubMed and Academic Search Complete were used with relevant terms. Findings consist of the major mechanisms of cocaine-induced vasoconstriction, endothelial dysfunction, and accelerated atherosclerosis, emphasizing acute, chronic, and secondary effects of cocaine. The etiology underlying cocaine's acute and chronic vascular effects is multifactorial, spanning hypertension, impaired homeostasis and platelet function, thrombosis, thromboembolism, and alterations in blood flow. Early detection of vascular disease in cocaine addiction by multimodality imaging is discussed. Treatment may be similar to indications in patients with traditional risk-factors, with few exceptions such as enhanced supportive care and use of benzodiazepines and phentolamine for sedation, and avoiding β-blockers. Given the vascular toxicity cocaine induces, further compounded by smoking and alcohol comorbidity, and interacting with aging of the crack generation, there is a public health imperative to identify pre-symptomatic markers of vascular impairments in cocaine addiction and employ preventive treatment to reduce silent disease progression. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Effectiveness of diffusion tensor imaging in differentiating early-stage subcortical ischemic vascular disease, Alzheimer's disease and normal ageing.

    Directory of Open Access Journals (Sweden)

    Min-Chien Tu

    of 73.8% in discriminating patients with SIVD from those with AD. In combined analysis of the patients with SIVD and AD (n = 75, the total FAB score was positively correlated with FA within the bilateral forceps minor, genu of the corpus callosum, left forceps major, left uncinate fasciculus, and right inferior longitudinal fasciculus (p = 0.001 ~ 0.038, and inversely correlated with MD within the right superior longitudinal fasciculus, genu and body of the corpus callosum, bilateral forceps minor, right uncinate fasciculus, and right inferior longitudinal fasciculus (p = 0.003 ~ 0.040.Our findings suggest the effectiveness of DTI measurements in distinguishing patients with early-stage AD from those with SIVD, with discernible changes in spatial distribution and magnitude of significance of the DTI parameters. Strategic FA assessments provided the most robust discriminative power to differentiate SIVD from AD, and FAB may serve as an additional cognitive marker. We also identified the neuronal substrates responsible for FAB performance.

  4. A biphasic endothelial stress-survival mechanism regulates the cellular response to vascular endothelial growth factor A

    International Nuclear Information System (INIS)

    Latham, Antony M.; Odell, Adam F.; Mughal, Nadeem A.; Issitt, Theo; Ulyatt, Clare; Walker, John H.; Homer-Vanniasinkam, Shervanthi; Ponnambalam, Sreenivasan

    2012-01-01

    Vascular endothelial growth factor A (VEGF-A) is an essential cytokine that regulates endothelial function and angiogenesis. VEGF-A binding to endothelial receptor tyrosine kinases such as VEGFR1 and VEGFR2 triggers cellular responses including survival, proliferation and new blood vessel sprouting. Increased levels of a soluble VEGFR1 splice variant (sFlt-1) correlate with endothelial dysfunction in pathologies such as pre-eclampsia; however the cellular mechanism(s) underlying the regulation and function of sFlt-1 are unclear. Here, we demonstrate the existence of a biphasic stress response in endothelial cells, using serum deprivation as a model of endothelial dysfunction. The early phase is characterized by a high VEGFR2:sFlt-1 ratio, which is reversed in the late phase. A functional consequence is a short-term increase in VEGF-A-stimulated intracellular signaling. In the late phase, sFlt-1 is secreted and deposited at the extracellular matrix. We hypothesized that under stress, increased endothelial sFlt-1 levels reduce VEGF-A bioavailability: VEGF-A treatment induces sFlt-1 expression at the cell surface and VEGF-A silencing inhibits sFlt-1 anchorage to the extracellular matrix. Treatment with recombinant sFlt-1 inhibits VEGF-A-stimulated in vitro angiogenesis and sFlt-1 silencing enhances this process. In this response, increased VEGFR2 levels are regulated by the phosphatidylinositol-3-kinase and PKB/Akt signaling pathways and increased sFlt-1 levels by the ERK1/2 signaling pathway. We conclude that during serum withdrawal, cellular sensing of environmental stress modulates sFlt-1 and VEGFR2 levels, regulating VEGF-A bioavailability and ensuring cell survival takes precedence over cell proliferation and migration. These findings may underpin an important mechanism contributing to endothelial dysfunction in pathological states. -- Highlights: ► Endothelial cells mount a stress response under conditions of low serum. ► Endothelial VEGFR levels are

  5. Optical spectroscopy of radiotherapy and photodynamic therapy responses in normal rat skin shows vascular breakdown products

    Science.gov (United States)

    Teles de Andrade, Cintia; Nogueira, Marcelo S.; Kanick, Stephen C.; Marra, Kayla; Gunn, Jason; Andreozzi, Jacqueline; Samkoe, Kimberley S.; Kurachi, Cristina; Pogue, Brian W.

    2016-03-01

    Photodynamic therapy (PDT) and radiotherapy are non-systemic cancer treatment options with different mechanisms of damage. So combining these techniques has been shown to have some synergy, and can mitigate their limitations such as low PDT light penetration or radiotherapy side effects. The present study monitored the induced tissue changes after PDT, radiotherapy, and a combination protocol in normal rat skin, using an optical spectroscopy system to track the observed biophysical changes. The Wistar rats were treated with one of the protocols: PDT followed by radiotherapy, PDT, radiotherapy and radiotherapy followed by PDT. Reflectance spectra were collected in order to observe the effects of these combined therapies, especially targeting vascular response. From the reflectance, information about oxygen saturation, met-hemoglobin and bilirubin concentration, blood volume fraction (BVF) and vessel radius were extracted from model fitting of the spectra. The rats were monitored for 24 hours after treatment. Results showed that there was no significant variation in the vessel size or BVF after the treatments. However, the PDT caused a significant increase in the met-hemoglobin and bilirubin concentrations, indicating an important blood breakdown. These results may provide an important clue on how the damage establishment takes place, helping to understand the effect of the combination of those techniques in order to verify the existence of a known synergistic effect.

  6. Exploring early public responses to geoengineering.

    Science.gov (United States)

    Pidgeon, Nick; Corner, Adam; Parkhill, Karen; Spence, Alexa; Butler, Catherine; Poortinga, Wouter

    2012-09-13

    Proposals for geoengineering the Earth's climate are prime examples of emerging or 'upstream' technologies, because many aspects of their effectiveness, cost and risks are yet to be researched, and in many cases are highly uncertain. This paper contributes to the emerging debate about the social acceptability of geoengineering technologies by presenting preliminary evidence on public responses to geoengineering from two of the very first UK studies of public perceptions and responses. The discussion draws upon two datasets: qualitative data (from an interview study conducted in 42 households in 2009), and quantitative data (from a subsequent nationwide survey (n=1822) of British public opinion). Unsurprisingly, baseline awareness of geoengineering was extremely low in both cases. The data from the survey indicate that, when briefly explained to people, carbon dioxide removal approaches were preferred to solar radiation management, while significant positive correlations were also found between concern about climate change and support for different geoengineering approaches. We discuss some of the wider considerations that are likely to shape public perceptions of geoengineering as it enters the media and public sphere, and conclude that, aside from technical considerations, public perceptions are likely to prove a key element influencing the debate over questions of the acceptability of geoengineering proposals.

  7. Early atherosclerosis and vascular inflammation in mice with diet-induced type 2 diabetes

    DEFF Research Database (Denmark)

    Bartels, E D; Bang, C A; Nielsen, L B

    2009-01-01

    and the median lesion area was 8.0 times higher than in fat-fed wild-type mice (P = 0.001). Intracellular adhesion molecule-1 staining of the aortic endothelium was most pronounced in the fat-fed apoB transgenic mice. CONCLUSIONS: Our findings suggest that diet-induced type 2 diabetes causes early......BACKGROUND: Obesity and type 2 diabetes increase the risk of atherosclerosis. It is unknown to what extent this reflects direct effects on the arterial wall or secondary effects of hyperlipidaemia. MATERIALS AND METHODS: The effect of obesity and type 2 diabetes on the development...

  8. Forearm cutaneous vascular and sudomotor responses to whole body passive heat stress in young smokers.

    Science.gov (United States)

    Moyen, Nicole E; Anderson, Hannah M; Burchfield, Jenna M; Tucker, Matthew A; Gonzalez, Melina A; Robinson, Forrest B; Ganio, Matthew S

    2015-07-01

    The purpose of this study was to compare smokers and nonsmokers' sudomotor and cutaneous vascular responses to whole body passive heat stress. Nine regularly smoking (SMK: 29 ± 9 yr; 10 ± 6 cigarettes/day) and 13 nonsmoking (N-SMK: 27 ± 8 yr) males were passively heated until core temperature (TC) increased 1.5°C from baseline. Forearm local sweat rate (LSR) via ventilated capsule, sweat gland activation (SGA), sweat gland output (SGO), and cutaneous vasomotor activity via laser-Doppler flowmetry (CVC) were measured as mean body temperature increased (ΔTb) during passive heating using a water-perfused suit. Compared with N-SMK, SMK had a smaller ΔTb at the onset of sweating (0.52 ± 0.19 vs. 0.35 ± 0.14°C, respectively; P = 0.03) and cutaneous vasodilation (0.61 ± 0.21 vs. 0.31 ± 0.12°C, respectively; P body heating was higher in N-SMK vs. SMK (1.00 ± 0.13 vs. 0.79 ± 0.26 mg·cm(-2)·min(-1); P = 0.03), which was likely a result of higher SGO (8.94 ± 3.99 vs. 5.94 ± 3.49 μg·gland(-1)·min(-1), respectively; P = 0.08) and not number of SGA (104 ± 7 vs. 121 ± 9 glands/cm(2), respectively; P = 0.58). During whole body passive heat stress, smokers had an earlier onset for forearm sweating and cutaneous vasodilation, but a lower local sweat rate that was likely due to lower sweat output per gland. These data provide insight into local (i.e., forearm) thermoregulatory responses of young smokers during uncompensatory whole body passive heat stress. Copyright © 2015 the American Physiological Society.

  9. Effect of preceding exercise on cerebral and splanchnic vascular responses to mental task

    Directory of Open Access Journals (Sweden)

    Someya Nami

    2012-06-01

    Full Text Available Abstract Background To investigate the effect of preceding acute exercise on the peripheral vascular response to a mental task, we measured splanchnic and cerebral blood flow responses to performing a mental task after exercise and resting. Methods In the exercise trial, 11 males exercised for 30 min on a cycle ergometer with a workload set at 70% of the age-predicted maximal heart rate for each individual. After a 15-min recovery period, the subjects rested for 5 min for pre-task baseline measurement and then performed mental arithmetic for 5 min followed by 5 min of post-task measurement. In the resting trial, they rested for 45 min and pre-task baseline data was obtained for 5 min. Then mental arithmetic was performed for 5 min followed by post-task measurement. We measured the mean blood velocity in the middle cerebral artery and superior mesenteric artery and the mean arterial pressure. Results Mean arterial pressure and mean blood velocity in the middle cerebral artery were significantly higher than the baseline during mental arithmetic in both exercise and resting trials. Mean blood velocity in the middle cerebral artery during mental arithmetic was greater in the control trial than the exercise trial. Mean blood velocity in the superior mesenteric artery showed no significant change during mental arithmetic from baseline in both trials. Conclusion These results suggest that acute exercise can moderate the increase in cerebral blood flow induced by a mental task.

  10. Rate of rise in diastolic blood pressure influences vascular sympathetic response to mental stress.

    Science.gov (United States)

    El Sayed, Khadigeh; Macefield, Vaughan G; Hissen, Sarah L; Joyner, Michael J; Taylor, Chloe E

    2016-12-15

    Research indicates that individuals may experience a rise (positive responders) or fall (negative responders) in muscle sympathetic nerve activity (MSNA) during mental stress. In this study, we examined the early blood pressure responses (including the peak, time of peak and rate of rise in blood pressure) to mental stress in positive and negative responders. Negative MSNA responders to mental stress exhibit a more rapid rise in diastolic pressure at the onset of the stressor, suggesting a baroreflex-mediated suppression of MSNA. In positive responders there is a more sluggish rise in blood pressure during mental stress, which appears to be MSNA-driven. This study suggests that whether MSNA has a role in the pressor response is dependent upon the reactivity of blood pressure early in the task. Research indicates that individuals may experience a rise (positive responders) or fall (negative responders) in muscle sympathetic nerve activity (MSNA) during mental stress. The aim was to examine the early blood pressure response to stress in positive and negative responders and thus its influence on the direction of change in MSNA. Blood pressure and MSNA were recorded continuously in 21 healthy young males during 2 min mental stressors (mental arithmetic, Stroop test) and physical stressors (cold pressor, handgrip exercise, post-exercise ischaemia). Participants were classified as negative or positive responders according to the direction of the mean change in MSNA during the stressor tasks. The peak changes, time of peak and rate of changes in blood pressure were compared between groups. During mental arithmetic negative responders experienced a significantly greater rate of rise in diastolic blood pressure in the first minute of the task (1.3 ± 0.5 mmHg s -1 ) compared with positive responders (0.4 ± 0.1 mmHg s -1 ; P = 0.03). Similar results were found for the Stroop test. Physical tasks elicited robust parallel increases in blood pressure and MSNA across

  11. Vascular Response to Intra-arterial Injury in the Thrombospondin-1 Null Mouse

    OpenAIRE

    Budhani, Faisal; Leonard, Katherine A.; Bergdahl, Andreas; Gao, Jimin; Lawler, Jack; Davis, Elaine C.

    2007-01-01

    Thrombospondin-1 (TSP-1) is a multifunctional, extracellular matrix protein that has been implicated in the regulation of smooth muscle cell proliferation, migration and differentiation during vascular development and injury. Vascular injury in wildtype and TSP-1 null mice was carried out by insertion of a straight spring guidewire into the femoral artery via a muscular arterial branch. Blood flow was restored after the muscular branch was ligated. The injury completely denuded the endotheliu...

  12. Characterization of early host responses in adults with dengue disease

    Directory of Open Access Journals (Sweden)

    Ling Ling

    2011-08-01

    Full Text Available Abstract Background While dengue-elicited early and transient host responses preceding defervescence could shape the disease outcome and reveal mechanisms of the disease pathogenesis, assessment of these responses are difficult as patients rarely seek healthcare during the first days of benign fever and thus data are lacking. Methods In this study, focusing on early recruitment, we performed whole-blood transcriptional profiling on denguevirus PCR positive patients sampled within 72 h of self-reported fever presentation (average 43 h, SD 18.6 h and compared the signatures with autologous samples drawn at defervescence and convalescence and to control patients with fever of other etiology. Results In the early dengue fever phase, a strong activation of the innate immune response related genes were seen that was absent at defervescence (4-7 days after fever debut, while at this second sampling genes related to biosynthesis and metabolism dominated. Transcripts relating to the adaptive immune response were over-expressed in the second sampling point with sustained activation at the third sampling. On an individual gene level, significant enrichment of transcripts early in dengue disease were chemokines CCL2 (MCP-1, CCL8 (MCP-2, CXCL10 (IP-10 and CCL3 (MIP-1α, antimicrobial peptide β-defensin 1 (DEFB1, desmosome/intermediate junction component plakoglobin (JUP and a microRNA which may negatively regulate pro-inflammatory cytokines in dengue infected peripheral blood cells, mIR-147 (NMES1. Conclusions These data show that the early response in patients mimics those previously described in vitro, where early assessment of transcriptional responses has been easily obtained. Several of the early transcripts identified may be affected by or mediate the pathogenesis and deserve further assessment at this timepoint in correlation to severe disease.

  13. Vascular smooth muscle responsiveness to nitric oxide is reduced in healthy adults with increased adiposity.

    Science.gov (United States)

    Christou, Demetra D; Pierce, Gary L; Walker, Ashley E; Hwang, Moon-Hyon; Yoo, Jeung-Ki; Luttrell, Meredith; Meade, Thomas H; English, Mark; Seals, Douglas R

    2012-09-15

    Vascular smooth muscle responsiveness to nitric oxide, as assessed by nitroglycerin-induced dilation (NID), is impaired in clinical cardiovascular disease, but its relation to adiposity is unknown. We determined the relation of NID to total and abdominal adiposity in healthy adults varying widely in adiposity. In 224 men and women [age, 18-79 years; body mass index (BMI), 16.4-42.2 kg/m(2)], we measured NID (brachial artery dilation to 0.4 mg sublingual nitroglycerin), total body adiposity [BMI and percent body fat (percent BF via dual-energy X-ray absorptiometry)], and indexes of abdominal adiposity [waist circumference (WC) and waist-to-hip ratio (WHR)]. In a subgroup (n = 74), we also measured total abdominal fat (TAF), abdominal visceral fat (AVF), and subcutaneous fat (ASF) using computed tomography. Based on multiple linear regression, NID was negatively related to BMI [part correlation coefficient (r(part)) = -0.19, P = 0.004] and abdominal adiposity (WC, r(part) = -0.22; WHR, r(part) = -0.19; TAF, r(part) = -0.36; AVF, r(part) = -0.36; and ASF, r(part) = -0.30; all P ≤ 0.009) independent of sex, but only tended to be related to total percent BF (r(part) = -0.12, P = 0.07). In a subgroup of subjects with the highest compared with the lowest amount of AVF, NID was 35% lower (P = 0.003). Accounting for systolic blood pressure, HDL cholesterol, glucose, insulin resistance, adiponectin, and brachial artery diameter reduced or abolished some of the relations between NID and adiposity. In conclusion, NID is or tends to be negatively associated with measures of total adiposity (BMI and percent BF, respectively) but is consistently and more strongly negatively associated with abdominal adiposity. Adiposity may influence NID in part via other cardiovascular risk factors.

  14. Early growth and postprandial appetite regulatory hormone responses

    DEFF Research Database (Denmark)

    Perälä, Mia-Maria; Kajantie, Eero; Valsta, Liisa M

    2013-01-01

    Strong epidemiological evidence suggests that slow prenatal or postnatal growth is associated with an increased risk of CVD and other metabolic diseases. However, little is known whether early growth affects postprandial metabolism and, especially, the appetite regulatory hormone system. Therefore......, we investigated the impact of early growth on postprandial appetite regulatory hormone responses to two high-protein and two high-fat content meals. Healthy, 65-75-year-old volunteers from the Helsinki Birth Cohort Study were recruited; twelve with a slow increase in BMI during the first year of life......, early growth may have a role in programming appetite regulatory hormone secretion in later life. Slow early growth is also associated with higher postprandial insulin and TAG responses but not with incretin levels....

  15. Post-translational control of nitrate reductase activity responding to light and photosynthesis evolved already in the early vascular plants.

    Science.gov (United States)

    Nemie-Feyissa, Dugassa; Królicka, Adriana; Førland, Nina; Hansen, Margarita; Heidari, Behzad; Lillo, Cathrine

    2013-05-01

    Regulation of nitrate reductase (NR) by reversible phosphorylation at a conserved motif is well established in higher plants, and enables regulation of NR in response to rapid fluctuations in light intensity. This regulation is not conserved in algae NR, and we wished to test the evolutionary origin of the regulatory mechanism by physiological examination of ancient land plants. Especially a member of the lycophytes is of interest since their NR is candidate for regulation by reversible phosphorylation based on sequence analysis. We compared Selaginella kraussiana, a member of the lycophytes and earliest vascular plants, with the angiosperm Arabidopsis thaliana, and also tested the moss Physcomitrella patens. Interestingly, optimization of assay conditions revealed that S. kraussiana NR used NADH as an electron donor like A. thaliana, whereas P. patens NR activity depended on NADPH. Examination of light/darkness effects showed that S. kraussiana NR was rapidly regulated similar to A. thaliana NR when a differential (Mg(2+) contra EDTA) assay was used to reveal activity state of NR. This implies that already existing NR enzyme was post-translationally activated by light in both species. Light had a positive effect also on de novo synthesis of NR in S. kraussiana, which could be shown after the plants had been exposed to a prolonged dark period (7 days). Daily variations in NR activity were mainly caused by post-translational modifications. As for angiosperms, the post-translational light activation of NR in S. kraussiana was inhibited by 3-(3,4-dichlorophenyl)-1*1-dimethylurea (DCMU), an inhibitor of photosynthesis and stomata opening. Evolutionary, a post-translational control mechanism for NR have occurred before or in parallel with development of vascular tissue in land plants, and appears to be part of a complex mechanisms for coordination of CO2 and nitrogen metabolism in these plants. Copyright © 2013 Elsevier GmbH. All rights reserved.

  16. The value of primary vascular stents in management of early portal vein stenosis after liver transplantation

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    Wen-Tsan Chang

    2016-03-01

    Full Text Available If portal vein stenosis (PVS occurs within 1 month after liver transplantation (LT, especially within 1 week, it can be catastrophic and result in rapid loss of the grafts and mortality. Although surgical treatments have been considered standard treatment for PVS, patients are usually unable to receive operations or re-transplantations, because of their critical conditions and a shortage of grafts. Recently, primary percutaneous transhepatic portal vein stents (PTPS were suggested as alternative and less-invasive treatments of PVS. However, because lethal complications may follow these primary stent placements for patients in early stages after LT, primary PTPS placements for patients suffering PVS 1 month after LT has been suggested. From November 2009 to July 2015, 38 consecutive adult patients underwent LT at our institution. Among them, six recipients suffered PVS within 1 month after LT. Technical success was achieved in all six patients. Clinical success was obtained in two of the four patients suffering PVS within 1 week after LT, and in the other two patients suffering PVS>1 week after LT. All surviving patients and their grafts were in good condition, and their stents remained patent. Our experience showed that primary PTPS placements can be used to effectively treat patients with PVS encountered within 1 month, and even within 1 week, after LT with acceptable short-term results. However, possible fatal complications should be kept in mind. Long-term results of these procedures need further follow-up.

  17. Vascular development of the grapevine (Vitis vinifera L.) inflorescence rachis in response to flower number, plant growth regulators and defoliation.

    Science.gov (United States)

    Gourieroux, Aude M; Holzapfel, Bruno P; McCully, Margaret E; Scollary, Geoffrey R; Rogiers, Suzy Y

    2017-09-01

    The grapevine inflorescence is a determinate panicle and as buds emerge, shoot, flower and rachis development occur simultaneously. The growth and architecture of the rachis is determined by genetic and environmental factors but here we examined the role of flower and leaf number as well as hormones on its elongation and vascular development. The consequences of rachis morphology and vascular area on berry size and composition were also assessed. One week prior to anthesis, Merlot and Cabernet Sauvignon field vines were exposed to manual flower removal, exogenous plant growth regulators or pre-bloom leaf removal. Manual removal of half the flowers along the vertical axis of the inflorescence resulted in a shorter rachis in both cultivars. Conversely, inflorescences treated with gibberellic acid (GA 3 ) and the synthetic cytokinin, 6-benzylaminopurine (BAP) resulted in a longer rachis while pre-bloom removal of all leaves on the inflorescence-bearing shoot did not alter rachis length relative to untreated inflorescences. Across the treatments, the cross-sectional areas of the conducting xylem and phloem in the rachis were positively correlated to rachis girth, flower number at anthesis, bunch berry number, bunch berry fresh mass and bunch sugar content at harvest. Conversely, average berry size and sugar content were not linked to rachis vascular area. These data indicate that the morphological and vascular development of the rachis was more responsive to flower number and plant growth regulators than to leaf removal.

  18. Differences of Tc-99m HMPAO SPECT imaging in the early stage of subcortical vascular dementia compared with Alzheimer's disease

    International Nuclear Information System (INIS)

    Park, Kyung Won; Kang, Do Young; Park, Min Jeong; Cheon, Sang Myung; Cha, Jae Kwan; Kim, Sang Ho; Kim, Jae Woo

    2007-01-01

    The aim of this study is to assess the specific patterns of regional cerebral blood flow (rCBF) in patients with the early stage of subcortical vascular dementia (SVaD) and Alzheimer's disease (AD) using Tc-99m HMPAO SPECT, and to compare the differences between the two conditions. Sixteen SVaD, 46 AD and 12 control subjects participated in this study. We included the patients with SVaD and AD according to NINCDS-ADRDA and NINDS-AIREN criteria. They were all matched for age, education and clinical dementia rating scores. Three groups were evaluated by Tc-99m HMPAO SPECT using statistical parametric mapping (SPM) for measuring rCBF. The SPECT data of patients with SVaD and AD were compared with those of normal control subjects and then compared with each other. SPM analysis of the SPECT image showed significant perfusion deficits on the right temporal region and thalamus, left insula and superior temporal gyrus, both cingulate gyri and frontal subgyri in patients with SVaD and on the left supramarginal gyrus, superior temporal gyrus, postcentral gyrus and inferior parietal lobule, right fugiform gyrus and both cingulate gyri in AD compared with control subjects (uncorrected ρ < 0.01). SVaD patients revealed significant hypoperfusion in the right parahippocampal gyrus with cingulated gyrus, left insula and both frontal subgyral regions compared with AD (uncorrected ρ < 0.01). Our study shows characteristic and different pattern of perfusion deficits in patients with SVaD and AD, and these results may be helpful to discriminate the two conditions in the early stage of illness

  19. Evaluation of the vascular state of hepatic tumor with radioisotope angiography and blood pool scintigraphies (early and delayed)

    International Nuclear Information System (INIS)

    Aburano, Tamio; Tonami, Norihisa; Hisada, Kinichi

    1976-01-01

    Combined radioisotope examinations of hepatic tumors have been performed using α 1 -fetoprotein radioimmunoassay, radioisotope angiography of the liver, and some tumor positive imaging scintigraphies. However, with these methods, it is frequently impossible to differentiate metastatic cancers from benign focal lesions. Radioisotope angiography of the liver, and both early (5 min later)- and delayed (4 hours later) blood pool scintigraphies of the liver were done continuously after 10mCi of sup(99m)Tc-albumin intravenous injection, in cases of clearcut focal lesions on sup(99m)Tc-colloid liver scan. The relationships among these findings were examined. Four of seven cases with hepatoma and two of nine cases with metastatic cancer which had showed hypervascular findings on radioisotope angiogram showed clear blood pool activities in the area of focal defects on sup(99m)Tc-colloid scan although less than liver. On the other hand, none of hypovascular tumors on radioisotope angiogram showed blood pool activities. However, four hours later, in most malignant lesions, the lesion to liver activity ratio calculated from data processing system showed a much higher value than the ratio obtained 5 min later after injection, although two cases with benign focal lesions did not show such sequential change. The sequential evaluation of the vascular state of a hepatic tumor using radioisotope angiography and early-and delayed blood pool scintigraphies was supposed to be extremely useful for the elucidation of the nature of focal hepatic lesions on sup(99m)Tc-colloid scan, especially in differentiating hypovascular malignant- and benign lesions. (auth.)

  20.  Evaluation of the humoral and cellular immune responses after implantation of a PTFE vascular prosthesis.

    Science.gov (United States)

    Skóra, Jan; Pupka, Artur; Dorobisz, Andrzej; Barć, Piotr; Korta, Krzysztof; Dawiskiba, Tomasz

    2012-07-02

    The experiment was designed in order to determine the immunological processes that occur during the healing in synthetic vascular grafts, especially to establish the differences in the location of the complement system proteins between the proximal and distal anastomosis and the differences in the arrangement of inflammatory cells in those anastomoses. The understanding of those processes will provide a true basis for determining risk factors for complications after arterial repair procedures. The experiment was carried out on 16 dogs that underwent implantation of unilateral aorto-femoral bypass with expanded polytetrafluoroethylene (ePTFE). After 6 months all animals were euthanized to dissect the vascular grafts. Immunohistochemical assays and electron microscopic examinations were performed. Immunohistochemical findings in the structure of neointima between anastomoses of vascular prostheses demonstrated significant differences between humoral and cellular responses. The area of proximal anastomosis revealed the presence of fibroblasts, but no macrophages were detected. The histological structure of the proximal anastomosis indicates that inflammatory processes were ended during the prosthesis healing. The immunological response obtained in the distal anastomosis corresponded to the chronic inflammatory reaction with the presence of macrophages, myofibroblasts and deposits of complement C3. The identification of differences in the presence of macrophages and myofibroblasts and the presence of the C3 component between the anastomoses is the original achievement of the present study. In the available literature, no such significant differences have been shown so far in the humoral and cellular immune response caused by the presence of an artificial vessel in the arterial system.

  1. Exercise facilitates early recognition of cardiac and vascular remodeling in chronic thromboembolic pulmonary hypertension in swine.

    Science.gov (United States)

    Stam, Kelly; van Duin, Richard W B; Uitterdijk, André; Cai, Zongye; Duncker, Dirk J; Merkus, Daphne

    2018-03-01

    Chronic thromboembolic pulmonary hypertension (CTEPH) develops in 4% of patients after pulmonary embolism and is accompanied by an impaired exercise tolerance, which is ascribed to the increased right ventricular (RV) afterload in combination with a ventilation/perfusion (V/Q) mismatch in the lungs. The present study aimed to investigate changes in arterial Po 2 and hemodynamics in response to graded treadmill exercise during development and progression of CTEPH in a novel swine model. Swine were chronically instrumented and received multiple pulmonary embolisms by 1) microsphere infusion (Spheres) over 5 wk, 2) endothelial dysfunction by administration of the endothelial nitric oxide synthase inhibitor N ω -nitro-l-arginine methyl ester (L-NAME) for 7 wk, 3) combined pulmonary embolisms and endothelial dysfunction (L-NAME + Spheres), or 4) served as sham-operated controls (sham). After a 9 wk followup, embolization combined with endothelial dysfunction resulted in CTEPH, as evidenced by mean pulmonary artery pressures of 39.5 ± 5.1 vs. 19.1 ± 1.5 mmHg (Spheres, P swine to result in an exercise-induced increase in cardiac index. In conclusion, embolization in combination with endothelial dysfunction results in CTEPH in swine. Exercise increased RV afterload, exacerbated the V/Q mismatch, and unmasked RV dysfunction. NEW & NOTEWORTHY Here, we present the first double-hit chronic thromboembolic pulmonary hypertension swine model. We show that embolization as well as endothelial dysfunction is required to induce sustained pulmonary hypertension, which is accompanied by altered exercise hemodynamics and an exacerbated ventilation/perfusion mismatch during exercise.

  2. Response of photosynthetic carbon gain to ecosystem retrogression of vascular plants and mosses in the boreal forest.

    Science.gov (United States)

    Bansal, Sheel; Nilsson, Marie-Charlotte; Wardle, David A

    2012-07-01

    In the long-term absence of rejuvenating disturbances, forest succession frequently proceeds from a maximal biomass phase to a retrogressive phase characterized by reduced nutrient availability [notably nitrogen (N) and phosphorus (P)] and net primary productivity. Few studies have considered how retrogression induces changes in ecophysiological responses associated with photosynthetic carbon (C) gain, and only for trees. We tested the hypothesis that retrogression would negatively impact photosynthetic C gain of four contrasting species, and that this impact would be greater for vascular plants (i.e., trees and shrubs) than for non-vascular plants (i.e., mosses). We used a 5,000-year-old chronosequence of forested islands in Sweden, where retrogression occurs in the long-term absence of lightning-ignited wildfires. Despite fundamental differences in plant form and ecological niche among species, vascular plants and mosses showed similar ecophysiological responses to retrogression. The most common effects of retrogression were reductions in photosynthesis and respiration per unit foliar N, increases in foliar N, δ(13)C and δ(15)N, and decreases in specific leaf areas. In contrast, photosynthesis per unit mass or area generally did not change along the chronosequence, but did vary many-fold between vascular plants and mosses. The consistent increases in foliar N without corresponding increases in mass- or area-based photosynthesis suggest that other factor(s), such as P co-limitation, light conditions or water availability, may co-regulate C gain in retrogressive boreal forests. Against our predictions, traits of mosses associated with C and N were generally highly responsive to retrogression, which has implications for how mosses influence ecosystem processes in boreal forests.

  3. T-cell activation and early gene response in dogs.

    Directory of Open Access Journals (Sweden)

    Sally-Anne Mortlock

    Full Text Available T-cells play a crucial role in canine immunoregulation and defence against invading pathogens. Proliferation is fundamental to T-cell differentiation, homeostasis and immune response. Initiation of proliferation following receptor mediated stimuli requires a temporally programmed gene response that can be identified as immediate-early, mid- and late phases. The immediate-early response genes in T-cell activation engage the cell cycle machinery and promote subsequent gene activation events. Genes involved in this immediate-early response in dogs are yet to be identified. The present study was undertaken to characterise the early T-cell gene response in dogs to improve understanding of the genetic mechanisms regulating immune function. Gene expression profiles were characterised using canine gene expression microarrays and quantitative reverse transcription PCR (qRT-PCR, and paired samples from eleven dogs. Significant functional annotation clusters were identified following stimulation with phytohemagluttinin (PHA (5μg/ml, including the Toll-like receptor signaling pathway and phosphorylation pathways. Using strict statistical criteria, 13 individual genes were found to be differentially expressed, nine of which have ontologies that relate to proliferation and cell cycle control. These included, prostaglandin-endoperoxide synthase 2 (PTGS2/COX2, early growth response 1 (EGR1, growth arrest and DNA damage-inducible gene (GADD45B, phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1, V-FOS FBJ murine osteosarcoma viral oncogene homolog (FOS, early growth response 2 (EGR2, hemogen (HEMGN, polo-like kinase 2 (PLK2 and polo-like kinase 3 (PLK3. Differential gene expression was re-examined using qRT-PCR, which confirmed that EGR1, EGR2, PMAIP1, PTGS2, FOS and GADD45B were significantly upregulated in stimulated cells and ALAS2 downregulated. PTGS2 and EGR1 showed the highest levels of response in these dogs. Both of these genes are involved in

  4. Redox Signaling and Its Impact on Skeletal and Vascular Responses to Spaceflight

    Directory of Open Access Journals (Sweden)

    Candice G. T. Tahimic

    2017-10-01

    Full Text Available Spaceflight entails exposure to numerous environmental challenges with the potential to contribute to both musculoskeletal and vascular dysfunction. The purpose of this review is to describe current understanding of microgravity and radiation impacts on the mammalian skeleton and associated vasculature at the level of the whole organism. Recent experiments from spaceflight and ground-based models have provided fresh insights into how these environmental stresses influence mechanisms that are related to redox signaling, oxidative stress, and tissue dysfunction. Emerging mechanistic knowledge on cellular defenses to radiation and other environmental stressors, including microgravity, are useful for both screening and developing interventions against spaceflight-induced deficits in bone and vascular function.

  5. Redox Signaling and Its Impact on Skeletal and Vascular Responses to Spaceflight

    Science.gov (United States)

    Tahimic, Candice; Globus, Ruth K.

    2018-01-01

    Spaceflight entails exposure to numerous environmental challenges with the potential to contribute to both musculoskeletal and vascular dysfunction. The purpose of this review is to describe current understanding of microgravity and radiation impacts on the mammalian skeleton and associated vasculature at the level of the whole organism. Recent experiments from spaceflight and groundbased models have provided fresh insights into how these environmental stresses influence mechanisms that are related to redox signaling, oxidative stress, and tissue dysfunction. Emerging mechanistic knowledge on cellular defenses to radiation and other environmental stressors, including microgravity, are useful for both screening and developing interventions against spaceflight-induced deficits in bone and vascular function.

  6. Assessment of Carotid Intima-Media Thickness as an Early Marker Of Vascular Damage In Hypertensive Children.

    Science.gov (United States)

    Baroncini, Liz Andréa Villela; Sylvestre, Lucimary de Castro; Baroncini, Camila Varotto; Pecoits, Roberto

    2017-05-01

    The increased carotid intima-media thickness (CIMT) correlates with the presence of atherosclerosis in adults and describes vascular abnormalities in both hypertensive children and adolescents. To assess CIMT as an early marker of atherosclerosis and vascular damage in hypertensive children and adolescents compared with non-hypertensive controls and to evaluate the influence of gender, age, and body mass index (BMI) on CIMT on each group. Observational cohort study. A total of 133 hypertensive subjects (male, n = 69; mean age, 10.5 ± 4 years) underwent carotid ultrasound exam for assessment of CIMT. One hundred and twenty-one non-hypertensive subjects (male, n = 64; mean age, 9.8 ± 4.1 years) were selected as controls for gender, age (± 1 year), and BMI (± 10%). There were no significant difference regarding gender (p = 0.954) and age (p = 0.067) between groups. Hypertensive subjects had higher BMI when compared to control group (p = 0.004), although within the established range of 10%. Subjects in the hypertensive group had higher CIMT values when compared to control group (0.46 ± 0.05 versus 0.42 ± 0.05 mm, respectively, p valores de EMIC quando comparados ao grupo-controle (0,46 ± 0,05 versus 0,42 ± 0,05 mm, respectivamente, p valores da EMIC não foram influenciados por sexo, idade e IMC quando analisados em ambos os grupos separadamente (Teste t de Student para amostras independentes). De acordo com o coeficiente de determinação (R²) ajustado, apenas 11.7% das variações da EMIC são devidas às variações em cada grupo, incluindo idade, sexo e IMC. A espessura médio-intimal das carótidas apresentou-se aumentada em crianças e adolescentes hipertensos quando comparados ao grupo controle. A presença de hipertensão aumentou a EMIC independentemente de idade, sexo e IMC.

  7. Associations of Fetuin-A levels with vascular disease in type 2 diabetes patients with early diabetic nephropathy

    Directory of Open Access Journals (Sweden)

    Roos Marcel

    2010-09-01

    Full Text Available Abstract Background Ambigous results exist on fetuin-A as marker for vascular disease in type 2 diabetes. This study aims to define the role of fetuin-A as marker for micro- and macrovascular disease in a high risk population of patients with type 2 diabetes mellitus and early diabetic nephropathy. Methods Fetuin-A serum levels were assessed by ELISA in a cross-sectional setting in 153 patients with type 2 diabetes. Associations of fetuin-A with metabolic, inflammatory and vascular markers were studied. Atherosclerotic burden was assessed by ankle-brachial-index (ABI as well as detection of common carotid artery intima-media thickness (IMT. Results Levels of fetuin-A were lower in male than in female patients (0.49 ± 0.15 vs. 0.56 ± 0.20 g/L, p = 0.02. In addition, there was an inverse correlation with age (r = -0.20, P = 0.01. Bivariate correlations adjusted for age and gender revealed no significant correlations with metabolic parameters, except for a weak inverse correlation with serum adiponectin (r = -0.19, p = 0.02. Regarding parameters of micro- and macrovascular disease, fetuin-A was significantly associated with ABI (r = 0.18, p = 0.04, while there was no association with IMT (r = -0.07, p = n.s. Patients with an ABI 1.3 (0.43 ± 0.10 vs. 0.52 ± 0.17 vs. 0.54 ± 0.18 g/L p = 0.05. Neither GFR nor albuminuria were associated with fetuin-A serum levels. Patients with prevalent neuropathy did not have altered fetuin-A levels compared to diabetic controls. In step-wise logistic regression analysis including age, gender, HbA1c, total cholesterol, glomerular filtration rate and fetuin-A, only total cholesterol (β = 0.01, p = 0.02 and fetuin-A (β = -5.99, p = 0.03 proved to be independent predictors of an ABI Conclusions The results of this cross-sectional study suggest that lower fetuin-A levels are associated with macrovascular late complications in high-risk type 2 diabetes patients while there are no associations of fetuin-A with

  8. Early adversity and brain response to faces in young adulthood.

    Science.gov (United States)

    Lieslehto, Johannes; Kiviniemi, Vesa; Mäki, Pirjo; Koivukangas, Jenni; Nordström, Tanja; Miettunen, Jouko; Barnett, Jennifer H; Jones, Peter B; Murray, Graham K; Moilanen, Irma; Paus, Tomáš; Veijola, Juha

    2017-09-01

    Early stressors play a key role in shaping interindividual differences in vulnerability to various psychopathologies, which according to the diathesis-stress model might relate to the elevated glucocorticoid secretion and impaired responsiveness to stress. Furthermore, previous studies have shown that individuals exposed to early adversity have deficits in emotion processing from faces. This study aims to explore whether early adversities associate with brain response to faces and whether this association might associate with the regional variations in mRNA expression of the glucocorticoid receptor gene (NR3C1). A total of 104 individuals drawn from the Northern Finland Brith Cohort 1986 participated in a face-task functional magnetic resonance imaging (fMRI) study. A large independent dataset (IMAGEN, N = 1739) was utilized for reducing fMRI data-analytical space in the NFBC 1986 dataset. Early adversities were associated with deviant brain response to fearful faces (MANCOVA, P = 0.006) and with weaker performance in fearful facial expression recognition (P = 0.01). Glucocorticoid receptor gene expression (data from the Allen Human Brain Atlas) correlated with the degree of associations between early adversities and brain response to fearful faces (R 2  = 0.25, P = 0.01) across different brain regions. Our results suggest that early adversities contribute to brain response to faces and that this association is mediated in part by the glucocorticoid system. Hum Brain Mapp 38:4470-4478, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  9. Nitrate decreases xanthine oxidoreductase-mediated nitrite reductase activity and attenuates vascular and blood pressure responses to nitrite.

    Science.gov (United States)

    Damacena-Angelis, Célio; Oliveira-Paula, Gustavo H; Pinheiro, Lucas C; Crevelin, Eduardo J; Portella, Rafael L; Moraes, Luiz Alberto B; Tanus-Santos, Jose E

    2017-08-01

    Nitrite and nitrate restore deficient endogenous nitric oxide (NO) production as they are converted back to NO, and therefore complement the classic enzymatic NO synthesis. Circulating nitrate and nitrite must cross membrane barriers to produce their effects and increased nitrate concentrations may attenuate the nitrite influx into cells, decreasing NO generation from nitrite. Moreover, xanthine oxidoreductase (XOR) mediates NO formation from nitrite and nitrate. However, no study has examined whether nitrate attenuates XOR-mediated NO generation from nitrite. We hypothesized that nitrate attenuates the vascular and blood pressure responses to nitrite either by interfering with nitrite influx into vascular tissue, or by competing with nitrite for XOR, thus inhibiting XOR-mediated NO generation. We used two independent vascular function assays in rats (aortic ring preparations and isolated mesenteric arterial bed perfusion) to examine the effects of sodium nitrate on the concentration-dependent responses to sodium nitrite. Both assays showed that nitrate attenuated the vascular responses to nitrite. Conversely, the aortic responses to the NO donor DETANONOate were not affected by sodium nitrate. Further confirming these results, we found that nitrate attenuated the acute blood pressure lowering effects of increasing doses of nitrite infused intravenously in freely moving rats. The possibility that nitrate could compete with nitrite and decrease nitrite influx into cells was tested by measuring the accumulation of nitrogen-15-labeled nitrite ( 15 N-nitrite) by aortic rings using ultra-performance liquid chromatography tandem mass-spectrometry (UPLC-MS/MS). Nitrate exerted no effect on aortic accumulation of 15 N-nitrite. Next, we used chemiluminescence-based NO detection to examine whether nitrate attenuates XOR-mediated nitrite reductase activity. Nitrate significantly shifted the Michaelis Menten saturation curve to the right, with a 3-fold increase in the

  10. Lower limb vascular dysfunction in cyclists

    Directory of Open Access Journals (Sweden)

    Thiago Ayala Melo Di Alencar

    2013-06-01

    Full Text Available Sports-related vascular insufficiency affecting the lower limbs is uncommon, and early signs and symptoms can be confused with musculoskeletal injuries. This is also the case among professional cyclists, who are always at the threshold between endurance and excess training. The aim of this review was to analyze the occurrence of vascular disorders in the lower limbs of cyclists and to discuss possible etiologies. Eighty-five texts, including papers and books, published from 1950 to 2012, were used. According to the literature reviewed, some cyclists receive a late diagnosis of vascular dysfunction due to a lack of familiarity of the medical team with this type of dysfunction. Data revealed that a reduced blood flow in the external iliac artery, especially on the left, is much more common than in the femoral and popliteal arteries, and that vascular impairment is responsible for the occurrence of early fatigue and reduced performance in cycling.

  11. Early disrupted neurovascular coupling and changed event level hemodynamic response function in type 2 diabetes: an fMRI study.

    Science.gov (United States)

    Duarte, João V; Pereira, João M S; Quendera, Bruno; Raimundo, Miguel; Moreno, Carolina; Gomes, Leonor; Carrilho, Francisco; Castelo-Branco, Miguel

    2015-10-01

    Type 2 diabetes (T2DM) patients develop vascular complications and have increased risk for neurophysiological impairment. Vascular pathophysiology may alter the blood flow regulation in cerebral microvasculature, affecting neurovascular coupling. Reduced fMRI signal can result from decreased neuronal activation or disrupted neurovascular coupling. The uncertainty about pathophysiological mechanisms (neurodegenerative, vascular, or both) underlying brain function impairments remains. In this cross-sectional study, we investigated if the hemodynamic response function (HRF) in lesion-free brains of patients is altered by measuring BOLD (Blood Oxygenation Level-Dependent) response to visual motion stimuli. We used a standard block design to examine the BOLD response and an event-related deconvolution approach. Importantly, the latter allowed for the first time to directly extract the true shape of HRF without any assumption and probe neurovascular coupling, using performance-matched stimuli. We discovered a change in HRF in early stages of diabetes. T2DM patients show significantly different fMRI response profiles. Our visual paradigm therefore demonstrated impaired neurovascular coupling in intact brain tissue. This implies that functional studies in T2DM require the definition of HRF, only achievable with deconvolution in event-related experiments. Further investigation of the mechanisms underlying impaired neurovascular coupling is needed to understand and potentially prevent the progression of brain function decrements in diabetes.

  12. Aminolevulinic acid-photodynamic therapy combined with topically applied vascular disrupting agent vadimezan leads to enhanced antitumor responses.

    Science.gov (United States)

    Marrero, Allison; Becker, Theresa; Sunar, Ulas; Morgan, Janet; Bellnier, David

    2011-01-01

    The tumor vascular-disrupting agent (VDA) vadimezan (5,6-dimethylxanthenone-4-acetic acid, DMXAA) has been shown to potentiate the antitumor activity of photodynamic therapy (PDT) using systemically administered photosensitizers. Here, we characterized the response of subcutaneous syngeneic Colon26 murine colon adenocarcinoma tumors to PDT using the locally applied photosensitizer precursor aminolevulinic acid (ALA) in combination with a topical formulation of vadimezan. Diffuse correlation spectroscopy (DCS), a noninvasive method for monitoring blood flow, was utilized to determine tumor vascular response to treatment. In addition, correlative CD31-immunohistochemistry to visualize endothelial damage, ELISA to measure induction of tumor necrosis factor-alpha (TNF-α) and tumor weight measurements were also examined in separate animals. In our previous work, DCS revealed a selective decrease in tumor blood flow over time following topical vadimezan. ALA-PDT treatment also induced a decrease in tumor blood flow. The onset of blood flow reduction was rapid in tumors treated with both ALA-PDT and vadimezan. CD31-immunostaining of tumor sections confirmed vascular damage following topical application of vadimezan. Tumor weight measurements revealed enhanced tumor growth inhibition with combination treatment compared with ALA-PDT or vadimezan treatment alone. In conclusion, vadimezan as a topical agent enhances treatment efficacy when combined with ALA-PDT. This combination could be useful in clinical applications. © 2011 The Authors. Photochemistry and Photobiology © 2011 The American Society of Photobiology.

  13. Potentiation of the vascular response to kinins by inhibition of myocardial kininases.

    Science.gov (United States)

    Dendorfer, A; Wolfrum, S; Schäfer, U; Stewart, J M; Inamura, N; Dominiak, P

    2000-01-01

    Inhibitors of angiotensin I-converting enzyme (ACE) are very efficacious in the potentiation of the actions of bradykinin (BK) and are able to provoke a B(2) receptor-mediated vasodilation even after desensitization of this receptor. Because this activity cannot be easily explained only by an inhibition of kinin degradation, direct interactions of ACE inhibitors with the B(2) receptor or its signal transduction have been hypothesized. To clarify the significance of degradation-independent potentiation, we studied the vasodilatory effects of BK and 2 degradation-resistant B(2) receptor agonists in the isolated rat heart, a model in which ACE and aminopeptidase P (APP) contribute equally to the degradation of BK. Coronary vasodilation to BK and to a peptidic (B6014) and a nonpeptidic (FR190997) degradation-resistant B(2) agonist was assessed in the presence or absence of the ACE inhibitor ramiprilat, the APP inhibitor mercaptoethanol, or both. Ramiprilat or mercaptoethanol induced leftward shifts in the BK dose-response curve (EC(50)=3.4 nmol/L) by a factor of 4.6 or 4.9, respectively. Combined inhibition of ACE and APP reduced the EC(50) of BK to 0.18 nmol/L (ie, by a factor of 19) but potentiated the activity of B6014 (EC(50)=1.9 nmol/L) only weakly without altering that of FR190997 (EC(50)=0.34 nmol/L). Desensitization of B(2) receptors was induced by the administration of BK (0.2 micromol/L) or FR190997 (0.1 micromol/L) for 30 minutes; the vascular reactivity to ramiprilat or increasing doses of BK was tested thereafter. After desensitization with BK, but not FR190997, an additional application of ramiprilat provoked a B(2) receptor-mediated vasodilation. High BK concentrations were still effective at the desensitized receptor. The process of desensitization was not altered by ramiprilat. These results show that in this model, all potentiating actions of ACE inhibitors on kinin-induced vasodilation are exclusively related to the reduction in BK breakdown and are

  14. The Sheer Stress of Shear Stress: Responses of the Vascular Wall to a Haemodynamic Force

    NARCIS (Netherlands)

    C. Cheng (Caroline (Ka Lai))

    2006-01-01

    textabstractStudies in the hemodynamic field point to a strong relation between shear stress and the onset to vascular diseases such as atherosclerosis. Data from in vitro studies using sheared endothelial cells have provided insight into the possible mechanisms involved. However, the lack of an

  15. No effect of melatonin to modify surgical-stress response after major vascular surgery

    DEFF Research Database (Denmark)

    Kücükakin, B.; Wilhelmsen, M.; Lykkesfeldt, Jens

    2010-01-01

    A possible mechanism underlying cardiovascular morbidity after major vascular surgery may be the perioperative ischaemia-reperfusion with excessive oxygen-derived free-radical production and increased levels of circulating inflammatory mediators. We examined the effect of melatonin infusion during...... surgery and oral melatonin treatment for 3 days after surgery on biochemical markers of oxidative and inflammatory stress....

  16. Orthostatic intolerance and the cardiovascular response to early postoperative mobilization

    DEFF Research Database (Denmark)

    Bundgaard-Nielsen, M; Jørgensen, Christoffer Calov; Jørgensen, T B

    2009-01-01

    BACKGROUND: A key element in enhanced postoperative recovery is early mobilization which, however, may be hindered by orthostatic intolerance, that is, an inability to sit or stand because of symptoms of cerebral hypoperfusion as intolerable dizziness, nausea and vomiting, feeling of heat...... of orthostatic intolerance. In contrast, 8 (50%) and 2 (12%) patients were orthostatic intolerant at 6 and approximately 22 h after surgery, respectively. Before surgery, SAP, DAP, and TPR increased (P0.05) and Scv(O2) decreased (P... the preoperative evaluation (P>0.05). CONCLUSIONS: The early postoperative postural cardiovascular response is impaired after radical prostatectomy with a risk of orthostatic intolerance, limiting early postoperative mobilization. The pathogenic mechanisms include both impaired TPR and CO responses....

  17. Early response to psychological trauma--what GPs can do.

    Science.gov (United States)

    Wade, Darryl; Howard, Alexandra; Fletcher, Susan; Cooper, John; Forbes, David

    2013-09-01

    There is a high prevalence of psychological trauma exposure among primary care patients. General practitioners are well placed to provide appropriate support for patients coping with trauma. This article outlines an evidence-based early response to psychological trauma. Psychological first aid is the preferred approach in providing early assistance to patients who have experienced a traumatic event. General practitioners can be guided by five empirically derived principles in their early response: promoting a sense of safety, calming, self efficacy, connectedness and hope. Structured psychological interventions, including psychological debriefing, are not routinely recommended in the first few weeks following trauma exposure. General practitioner self care is an important aspect of providing post-trauma patient care.

  18. Serological response to Epstein-Barr virus early antigen is ...

    African Journals Online (AJOL)

    Serological response to Epstein-Barr virus early antigen is associated with gastric cancer and human immunodeficiency virus infection in Zambian adults: a ... EBV exposure is common among Zambian adults and that EBV EA seropositivity is associated with gastric cancer and HIV infection, but not premalignant lesions.

  19. Differential vascular dysfunction in response to diets of differing macronutrient composition: a phenomenonological study

    Directory of Open Access Journals (Sweden)

    Cassidy Roslyn

    2007-06-01

    Full Text Available Abstract Background Vascular dysfunction can develop from consumption of an energy-rich diet, even prior to the onset of obesity. However, the roles played by different dietary components remain uncertain. While attempting to develop models of obesity in a separate study, we observed that two high-energy diets of differing macronutrient compositions affected vascular function differently in overweight rats. Methods Male Wistar rats (n = 6/group were fed diets providing varying percentages of energy from fat and carbohydrate (CHO. For 10 weeks, they were fed either chow, as control diet (10% of energy from fat; 63% from CHO, chow supplemented with chocolate biscuit (30% fat; 56% CHO or a high-fat diet (45% fat; 35% CHO. Blood concentrations of biochemical markers of obesity were measured, and epididymal fat pads weighed as a measure of adiposity. Mesenteric arteries were dissected and their contractile and relaxant properties analysed myographically. Data were tested by analysis of variance (ANOVA. Results Weight gain and plasma concentrations of glucose, insulin and leptin were similar in all groups. However, biscuit-fed animals showed increased food intake (+27%; p p p p p Conclusion Vascular dysfunction resulting from consumption of a high-fat or combined relatively high-fat/high-CHO diet occurs through different physiological processes, which may be attributable to their differing macronutrient compositions. Combining potentially atherogenic macronutrients induces more extensive vascular impairment than that of high-fat alone, and may be attributable to the more marked dyslipidaemia observed with such a diet. Thus, these findings help clarify the role of dietary components in vascular impairment, which has implications for clinical approaches to preventing cardiovascular disease.

  20. The early medical response to the Goiania accident

    International Nuclear Information System (INIS)

    Valverde, N.J.; Oliveira, A.R.

    2000-01-01

    The Goiania accident was the most severe radiological one that ever happened in the western hemisphere. The response to its human, social, environmental, economical and psychological burdens represented a huge challenge. Thanks to a multi-institutional intervention the consequences of the accident were greatly minimised. The medical response followed the same pattern and was based on a three-level system of progressive assistance. The early medical response encompassed medical and 'radiological' triage, admission to a specially prepared ward of a local hospital and treatment at a reference center in Rio de Janeiro. (author)

  1. Influence of myocardial oxygen demand on the coronary vascular response to arterial blood gas changes in humans.

    Science.gov (United States)

    Vermeulen, Tyler Dennis; Boulet, Lindsey M; Stembridge, Mike; Williams, Alexandra Mackenzie; Anholm, James D; Subedi, Prajan; Gasho, Chris; Ainslie, Philip N; Feigl, Eric O; Foster, Glen Edward

    2018-03-30

    It remains unclear if the human coronary vasculature is inherently sensitive to changes in arterial PO 2 and PCO 2 or if coronary vascular responses are the result of concomitant increases in myocardial O 2 consumption/demand (MVO 2 ). We hypothesized that the coronary vascular response to PO 2 and PCO 2 would be attenuated in healthy men when MVO 2 was attenuated with β 1 -adrenergic receptor blockade. Healthy men (n=11; age: 25 {plus minus} 1 years) received intravenous esmolol (β 1 -adrenergic receptor antagonist) or volume-matched saline in a double-blind, randomized, crossover study, and were exposed to poikilocapnic hypoxia, isocapnic hypoxia, and hypercapnic hypoxia. Measurements made at baseline and following 5-min of steady state at each gas manipulation included left anterior descending coronary blood velocity (LAD V ; Doppler echocardiography), heart rate and arterial blood pressure. LAD V values at the end of each hypoxic condition were compared between esmolol and placebo. Rate pressure product (RPP) and left-ventricular mechanical energy (ME LV ) were calculated as indices of MVO 2 . All gas manipulations augmented RPP, ME LV , and LAD V but only RPP and ME LV were attenuated (4-18%) following β 1 -adrenergic receptor blockade (P<0.05). Despite attenuated RPP and MELV responses, β 1 -adrenergic receptor blockade did not attenuate the mean LADV vasodilatory response when compared to placebo during poikilocapnic hypoxia (29.4{plus minus}2.2 vs. 27.3{plus minus}1.6 cm/s) and isocapnic hypoxia (29.5{plus minus}1.5 vs. 30.3{plus minus}2.2 cm/s). Hypercapnic hypoxia elicited a feed-forward coronary dilation that was blocked by β 1 -adrenergic receptor blockade. These results indicate a direct influence of arterial PO 2 on coronary vascular regulation that is independent of MVO 2 .

  2. Characteristic pattern of cerebral perfusion in patients with the early stage of subcortical vascular dementia compared with Alzheimer's disease

    International Nuclear Information System (INIS)

    Jeong, Young Jin; Kang, Do Young; Park, Kyung Won; Cheon, Sang Myung; Kim, Jong Kuk; Kim, Jae Woo

    2004-01-01

    Brain perfusion SPECT has been commonly used to evaluate several different types of dementia. The aim of this study is to assess the specific patterns of regional cerebral blood flow (rCBF) in patients with the early stage of subcortical vascular dementia (SVD) and Alzheimer's disease (AD) using Tc-99m HMPAO SPECT, and to compare the differences between the two conditions. Sixteen SVD (mean age; 68.0±7.0 years, educational period; 6.3±5.6 years, CDR; 0.80±0.26). 46 AD (mean age; 69.9±7.4 years, educational period; 5.4±4.7 years, CDR; 0.86±0.23) and 12 normal control subjects (mean age; 67.1±7.7 years, educational period; 6.2±4.2 years) participated in this study. We included the patients with SVD and AD according to NINCDS-ADRDA criteria for probable AD and NINDS-AIREN criteria for probable or possible VD. They were all matched for age, education and clinical dementia scale scores. SPM analysis of the SPECT image showed significant perfusion deficits on the right temporal region and right thalamus, left insula and superior temporal gyrus, both cingulate gyri and frontal subgyral regions in patients with SVD and on the left supramarginal gyrus, superior temporal gyrus, postcentral gyrus and inferior parietal lobule, right fugiform gyrus and both cingulate gyri in patients with AD compared with control subjects (uncorrected p<0.01). SVD patients revealed significant hypoperfusion in the right parahippocampal gyrus, right cingulated gyrus, left insula, and both frontal subgyral regions compared with AD patients (uncorrected p<0.01). SVD patients revealed significant hyperperfusion in right superior frontal gyrus, left pre- and postcentral gyri, left paracentral lobule, left precuneus and both medial frontal gyri compared with AD patients (uncorrected p<0.01). Our study shows characteristic and different pattern of perfusion deficits in patients with SVD and AD, and these results may be helpful to discriminate the two conditions in the early stage of illness

  3. Changes in Ultrasonographic Vascularity Upon Initiation of Adalimumab Combination Therapy in Rheumatoid Arthritis Patients With an Inadequate Response to Methotrexate.

    Science.gov (United States)

    Kaeley, Gurjit S; Nishio, Midori J; Goyal, Janak R; MacCarter, Daryl K; Wells, Alvin F; Chen, Su; Kupper, Hartmut; Kalabic, Jasmina

    2016-11-01

    To assess joint disease activity by ultrasound (US) in patients with rheumatoid arthritis (RA) initiating treatment with adalimumab (ADA) plus methotrexate (MTX). Data for this post hoc analysis originated from the MUSICA trial (ClinicalTrials.gov identifier: NCT01185288), which evaluated the efficacy of initiating ADA (40 mg every other week) plus 7.5 or 20 mg/week MTX in 309 patients with RA with an inadequate response to MTX. Synovial vascularization over 24 weeks was assessed bilaterally at metacarpophalangeal joint 2 (MCP2), MCP3, MCP5, metatarsophalangeal joint 5, and the wrists by power Doppler US (PDUS). A semiquantitative 4-grade scale was used. Disease activity was assessed using the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) and Simplified Disease Activity Index (SDAI). The correlation between continuous variables was assessed using Pearson's correlation coefficient. After 24 weeks of treatment with ADA plus MTX, rapid improvements in the mean synovial vascularity score were observed; the greatest improvements were in MCP2 (-0.5), MCP3 (-0.4), and the wrist (-0.4). At week 24, patients with the lowest DAS28-CRP ( 0.9). Synovial vascularity scores correlated poorly with DAS28, swollen joint count in 66 joints (SJC66), SJC28, tender joint count in 68 joints (TJC68), TJC28, Clinical Disease Activity Index (CDAI), SDAI, physician's global assessment, patient's global assessment of pain, and disease duration (ρ < 0.2). Thirty-two (70%) of 46 patients with a DAS28-CRP of <2.6, and 11 (58%) of 19 patients with an SDAI indicating remission had at least 1 joint with a synovial vascularity score of ≥1. PDUS detects changes in synovial vascularity in RA patients treated with ADA plus MTX, and residual synovial vascularity in patients in whom clinical disease control has been achieved. © 2016 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.

  4. Endothelial Dll4 overexpression reduces vascular response and inhibits tumor growth and metastasization in vivo.

    Science.gov (United States)

    Trindade, Alexandre; Djokovic, Dusan; Gigante, Joana; Mendonça, Liliana; Duarte, António

    2017-03-14

    The inhibition of Delta-like 4 (Dll4)/Notch signaling has been shown to result in excessive, nonfunctional vessel proliferation and significant tumor growth suppression. However, safety concerns emerged with the identification of side effects resulting from chronic Dll4/Notch blockade. Alternatively, we explored the endothelial Dll4 overexpression using different mouse tumor models. We used a transgenic mouse model of endothelial-specific Dll4 overexpression, previously produced. Growth kinetics and vascular histopathology of several types of solid tumors was evaluated, namely Lewis Lung Carcinoma xenografts, chemically-induced skin papillomas and RIP1-Tag2 insulinomas. We found that increased Dll4/Notch signaling reduces tumor growth by reducing vascular endothelial growth factor (VEGF)-induced endothelial proliferation, tumor vessel density and overall tumor blood supply. In addition, Dll4 overexpression consistently improved tumor vascular maturation and functionality, as indicated by increased vessel calibers, enhanced mural cell recruitment and increased network perfusion. Importantly, the tumor vessel normalization is not more effective than restricted vessel proliferation, but was found to prevent metastasis formation and allow for increased delivery to the tumor of concomitant chemotherapy, improving its efficacy. By reducing endothelial sensitivity to VEGF, these results imply that Dll4/Notch stimulation in tumor microenvironment could be beneficial to solid cancer patient treatment by reducing primary tumor size, improving tumor drug delivery and reducing metastization. Endothelial specific Dll4 overexpression thus appears as a promising anti-angiogenic modality that might improve cancer control.

  5. Near-infrared spectroscopy can detect differences in vascular responsiveness to a hyperglycaemic challenge in individuals with obesity compared to normal-weight individuals.

    Science.gov (United States)

    Soares, Rogério Nogueira; Reimer, Raylene A; Alenezi, Zaid; Doyle-Baker, Patricia K; Murias, Juan Manuel

    2018-01-01

    To examine whether the near-infrared spectroscopy combined with vascular occlusion test technique could detect differences in vascular responsiveness during hyperglycaemia between normal-weight individuals and individuals with obesity. A total of 16 normal-weight individuals (body mass index, 21.3 ± 1.7 kg/m 2 ) and 13 individuals with obesity (body mass index, 34.4 ± 2.0 kg/m 2 ) were submitted to five vascular occlusion tests (Pre, 30, 60, 90 and 120 min after glucose challenge). Vascular responsiveness was determined by the Slope 2 (Slope 2 StO 2 ) and the area under the curve (StO 2AUC ) of oxygen saturation derived from near-infrared spectroscopy-vascular occlusion test. The Slope 2 StO 2 increased from 1.07 ± 0.16%/s (Pre) to 1.53 ± 0.21%/s at 90 min ( p obese it increased from 0.71 ± 0.09%/s (Pre) to 0.92 ± 0.14%/s at 60 min ( p obesity. Near-infrared spectroscopy-vascular occlusion test technique was capable of detecting differences in vascular responsiveness during hyperglycaemia between normal-weight individuals and individuals with obesity.

  6. Individual responsibility in early detection of prostate gland cancer

    International Nuclear Information System (INIS)

    Nodal Laugart, Ramon Lemay; Rodriguez Ardi, Maricel; Tamayo Tamayo, Iser

    2011-01-01

    Starting from the point that morbidity and mortality rate due to prostate gland cancer has increased in Santiago de Cuba, the authors of this work decided to analyze the relation to individual responsibility in order to early detect the aforementioned condition. Therefore, 48 men over 50 years old belonging to the health area of Frank Pais Garcia University Polyclinic in Santiago de Cuba were surveyed during the first months of the year 2011 to determine the factors that influenced on the low risk perception. Results showed the urgent need of carrying out actions of health promotion and disease prevention in order to achieve the individual feels more responsible of his health care. Of the case material, 85,4 % participants admitted they did not have the tests to guarantee the early diagnosis or detect this tumor.(author)

  7. Decreased heart rate variability responses during early postoperative mobilization

    DEFF Research Database (Denmark)

    Jans, Øivind; Brinth, Louise; Kehlet, Henrik

    2015-01-01

    in relation to postural change. METHODS: A standardized mobilization protocol before, 6 and 24 h after surgery was performed in 23 patients scheduled for elective THA. Beat-to-beat arterial blood pressure was measured by photoplethysmography and HRV was derived from pulse wave interbeat intervals and analysed......BACKGROUND: Intact orthostatic blood pressure regulation is essential for early mobilization after surgery. However, postoperative orthostatic hypotension and intolerance (OI) may delay early ambulation. The mechanisms of postoperative OI include impaired vasopressor responses relating...... and postural responses in arterial pressures decreased compared to preoperative conditions. During standing HF variation increased by 16.7 (95 % CI 8.0-25.0) normalized units (nu) at 6 h and 10.7 (2.0-19.4) nu at 24 h compared to the preoperative evaluation. At 24 h the LF/HF ratio decreased from 1.8 (1...

  8. Effect of prostaglandin inhibition on the renal vascular response to ionic and non-ionic contrast media in the dog

    International Nuclear Information System (INIS)

    Lund, G.; Einzig, S.; Rysavy, J.; Salomonowitz, E.; Castaneda-Zuniga, W.; Amplatz, K.; Minnesota Univ., Minneapolis

    1984-01-01

    In an attempt to study the role of prostaglandins in the renal vascular response to contrast media in mongrel dogs, renal arterial injections of 6 ml of either the non-ionic contrast medium Iopamidol or the ionic medium diatrizoate meglumine/Na + were performed, before and after intravenous injection of a buffered solution of acetyl-salicylic acid (10 mg/kg) (ASA). Renal blood flow was recorded using non-occluding electromagnetic flow probes. The resting renal blood flow was significantly reduced after ASA. The usual biphasic response to contrast injection was observed both before and after ASA, and using either contrast medium. Analysis of the results failed to show any difference in degree of vasodilation or vasoconstriction after ASA. We conclude that prostaglandins may affect the resting level of renal blood flow but are not mediators of the instantaneous changes in response to contrast injection. (orig.)

  9. Evaluation of early imaging response criteria in glioblastoma multiforme

    International Nuclear Information System (INIS)

    Gladwish, Adam; Koh, Eng-Siew; Hoisak, Jeremy; Lockwood, Gina; Millar, Barbara-Ann; Mason, Warren; Yu, Eugene; Laperriere, Normand J; Ménard, Cynthia

    2011-01-01

    Early and accurate prediction of response to cancer treatment through imaging criteria is particularly important in rapidly progressive malignancies such as Glioblastoma Multiforme (GBM). We sought to assess the predictive value of structural imaging response criteria one month after concurrent chemotherapy and radiotherapy (RT) in patients with GBM. Thirty patients were enrolled from 2005 to 2007 (median follow-up 22 months). Tumor volumes were delineated at the boundary of abnormal contrast enhancement on T1-weighted images prior to and 1 month after RT. Clinical Progression [CP] occurred when clinical and/or radiological events led to a change in chemotherapy management. Early Radiologic Progression [ERP] was defined as the qualitative interpretation of radiological progression one month post-RT. Patients with ERP were determined pseudoprogressors if clinically stable for ≥6 months. Receiver-operator characteristics were calculated for RECIST and MacDonald criteria, along with alternative thresholds against 1 year CP-free survival and 2 year overall survival (OS). 13 patients (52%) were found to have ERP, of whom 5 (38.5%) were pseudoprogressors. Patients with ERP had a lower median OS (11.2 mo) than those without (not reached) (p < 0.001). True progressors fared worse than pseudoprogressors (median survival 7.2 mo vs. 19.0 mo, p < 0.001). Volume thresholds performed slightly better compared to area and diameter thresholds in ROC analysis. Responses of > 25% in volume or > 15% in area were most predictive of OS. We show that while a subjective interpretation of early radiological progression from baseline is generally associated with poor outcome, true progressors cannot be distinguished from pseudoprogressors. In contrast, the magnitude of early imaging volumetric response may be a predictive and quantitative metric of favorable outcome

  10. Association of Genetic Variants With Response to Anti-Vascular Endothelial Growth Factor Therapy in Age-Related Macular Degeneration.

    Science.gov (United States)

    Lorés-Motta, Laura; Riaz, Moeen; Grunin, Michelle; Corominas, Jordi; van Asten, Freekje; Pauper, Marc; Leenders, Mathieu; Richardson, Andrea J; Muether, Philipp; Cree, Angela J; Griffiths, Helen L; Pham, Connie; Belanger, Marie-Claude; Meester-Smoor, Magda A; Ali, Manir; Heid, Iris M; Fritsche, Lars G; Chakravarthy, Usha; Gale, Richard; McKibbin, Martin; Inglehearn, Chris F; Schlingemann, Reinier O; Omar, Amer; Chen, John; Koenekoop, Robert K; Fauser, Sascha; Guymer, Robyn H; Hoyng, Carel B; de Jong, Eiko K; Lotery, Andrew J; Mitchell, Paul; den Hollander, Anneke I; Baird, Paul N; Chowers, Itay

    2018-05-31

    Visual acuity (VA) outcomes differ considerably among patients with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (VEGF) drugs. Identification of pharmacogenetic associations may help clinicians understand the mechanisms underlying this variability as well as pave the way for personalized treatment in nAMD. To identify genetic factors associated with variability in the response to anti-VEGF therapy for patients with nAMD. In this multicenter genome-wide association study, 678 patients with nAMD with genome-wide genotyping data were included in the discovery phase; 1380 additional patients with nAMD were genotyped for selected common variants in the replication phase. All participants received 3 monthly injections of bevacizumab or ranibizumab. Clinical data were evaluated for inclusion/exclusion criteria from October 2014 to October 2015, followed by data analysis from October 2015 to February 2016. For replication cohort genotyping, clinical data collection and analysis (including meta-analysis) was performed from March 2016 to April 2017. Change in VA after the loading dose of 3 monthly anti-VEGF injections compared with baseline. Of the 2058 included patients, 1210 (58.8%) were women, and the mean (SD) age across all cohorts was 78 (7.4) years. Patients included in the discovery cohort and most of the patients in the replication cohorts were of European descent. The mean (SD) baseline VA was 51.3 (20.3) Early Treatment Diabetic Retinopathy Study (ETDRS) score letters, and the mean (SD) change in VA after the loading dose of 3 monthly injections was a gain of 5.1 (13.9) ETDRS score letters (ie, 1-line gain). Genome-wide single-variant analyses of common variants revealed 5 independent loci that reached a P value less than 10 × 10-5. After replication and meta-analysis of the lead variants, rs12138564 located in the CCT3 gene remained nominally associated with a better treatment outcome (ETDRS letter

  11. Experimental substantiation of a method of early diagnosis of infectivity of vascular prostheses with the help of 99mTc-leukocytes

    International Nuclear Information System (INIS)

    Zatevakhin, I.I.; Malov, G.A.; Govorunov, G.V.; Dobronravov, D.S.; Makhmudov, S.Ya.; Komrakov, V.E.

    1988-01-01

    Experiments on 9 dogs were staged for a study of a method of early diagnosis of infectivity of vascular prostheses of the abdominal aorta with the help of 99m Tc-labeled leukocytes. A sterile synthetic vascular prosthesis was used for prosthetics of the abdominal aorta in the 1st control group of animals, a prosthesis, previously infected with St. aureus, was used in the 2nd group, a sterile prosthesis with its subsequent infecting by i.v. injection of St. aureus was used in the 3rd group. The tolre of antibiotic therapy in infectivity of vascular prostheses was studied on the animals of the 3rd group. A radionuclide study with autologous 99m Tc-labeled leukocytes was conducted using the Deina-2 camera (Picker). Visualization of the prostheses was unobserved in the 1st control group; in the 2nd group the accumulation of 99m Tc-leucocytes in the zone of the prosthesis and its vizualization on the 4th-5th min. were noted; in the 3rd group the prothesis was visualized on the 10th-15th min. After antibiotic therapy in the 3rd group visualization of the prothesis was undetectable. The proposed method permitted visualization of a zone of infection in the early postoperative period, observation of the time course of infection development, and assessment of the efficacy of antibiotic therapy

  12. Cutaneous vascular and core temperature responses to sustained cold exposure in hypoxia.

    Science.gov (United States)

    Simmons, Grant H; Barrett-O'Keefe, Zachary; Minson, Christopher T; Halliwill, John R

    2011-10-01

    We tested the effect of hypoxia on cutaneous vascular regulation and defense of core temperature during cold exposure. Twelve subjects had two microdialysis fibres placed in the ventral forearm and were immersed to the sternum in a bathtub on parallel study days (normoxia and poikilocapnic hypoxia with an arterial O(2) saturation of 80%). One fibre served as the control (1 mM propranolol) and the other received 5 mM yohimbine (plus 1 mM propranolol) to block adrenergic receptors. Skin blood flow was assessed at each site (laser Doppler flowmetry), divided by mean arterial pressure to calculate cutaneous vascular conductance (CVC), and scaled to baseline. Cold exposure was first induced by a progressive reduction in water temperature from 36 to 23°C over 30 min to assess cutaneous vascular regulation, then by clamping the water temperature at 10°C for 45 min to test defense of core temperature. During normoxia, cold stress reduced CVC in control (-44 ± 4%) and yohimbine sites (-13 ± 7%; both P cooling but resulted in greater reductions in CVC in control (-67 ± 7%) and yohimbine sites (-35 ± 11%) during cooling (both P cooling rate during the second phase of cold exposure was unaffected by hypoxia (-1.81 ± 0.23°C h(-1) in normoxia versus -1.97 ± 0.33°C h(-1) in hypoxia; P > 0.05). We conclude that hypoxia increases cutaneous (non-noradrenergic) vasoconstriction during prolonged cold exposure, while core cooling rate is not consistently affected.

  13. Low Prevalence and Clinical Effect of Vascular Risk Factors in Early-Onset Alzheimer’s Disease

    Science.gov (United States)

    Chen, Yaohua; Sillaire, Adeline Rollin; Dallongeville, Jean; Skrobala, Emilie; Wallon, David; Dubois, Bruno; Hannequin, Didier; Pasquier, Florence; Bombois, Stéphanie; Boutantin, Justine; Cassagnaud, Pascaline; Chen, Yaohua; Delbeuck, Xavier; Delmaire, Christine; Deramecourt, Vincent; Gele, Patrick; Houssein-Foucher, Claude; Jacquemont, Charlotte; Lebert, Florence; Lebouvier, Thibaud; Lopez, Renaud; Mackowiak, Marie-Anne; Maureille, Aurélien; Pasquier, Florence; Petyt, Grégory; Pollet, Marianne; Rollin-Sillaire, Adeline; Schraen, Susanna; Semah, Franck; Vanhoutte, Matthieu

    2017-01-01

    Background: Determinants of early-onset Alzheimer’s disease (EOAD) are not well known. In late-onset AD, vascular risk factors (VRFs) are associated with earlier clinical manifestation. Objective: The objective of this study was to assess the putative association between VRFs and EOAD. Methods: We studied participants with dementia meeting criteria for EOAD (recruited into the French CoMAJ prospective cohort study from 1 June 2009 to 28 February 2014) and age-, gender-matched controls (ratio 1:3, drawn randomly from the French MONA-LISA population-based survey between 2005 and 2007). Demographic data, VRFs, comorbidities, treatments, and APOE genotypes were compared in multivariable logistic regression analyses. Results: We studied 102 participants with dementia (mean±standard deviation age: 59.5±3.8; women: 59.8%) and 306 controls. Compared with controls, EOAD participants had spent less time in formal education (9.9±2.9 versus 11.7±3.8 y; p < 0.0001), were less likely to be regular alcohol consumers (p < 0.0001), had a lower body mass index (–2 kg/m2; p < 0.0004), and a lower mean systolic blood pressure (–6.2 mmHg; p = 0.0036). The prevalence of APOE ɛ4 allele was higher in participants with dementia than in controls (50% versus 29.4%; p = 0.0002), as was the prevalence of depression (48% versus 32%; p < 0.001). Similar results were observed in multivariable analysis. Compared with EOAD participants lacking VRFs, EOAD participants with at least one VRF had a higher prevalence of depression (29.6% versus 53.3%, respectively; p = 0.03). Conclusion: The prevalence of VRFs is not elevated in EOAD patients (in contrast to older AD patients). Extensive genetic testing should be considered more frequently in the context of EOAD. PMID:28984595

  14. A key role for the endothelium in NOD1 mediated vascular inflammation: comparison to TLR4 responses.

    Directory of Open Access Journals (Sweden)

    Timothy Gatheral

    Full Text Available Understanding the mechanisms by which pathogens induce vascular inflammation and dysfunction may reveal novel therapeutic targets in sepsis and related conditions. The intracellular receptor NOD1 recognises peptidoglycan which features in the cell wall of gram negative and some gram positive bacteria. NOD1 engagement generates an inflammatory response via activation of NFκB and MAPK pathways. We have previously shown that stimulation of NOD1 directly activates blood vessels and causes experimental shock in vivo. In this study we have used an ex vivo vessel-organ culture model to characterise the relative contribution of the endothelium in the response of blood vessels to NOD1 agonists. In addition we present the novel finding that NOD1 directly activates human blood vessels. Using human cultured cells we confirm that endothelial cells respond more avidly to NOD1 agonists than vascular smooth muscle cells. Accordingly we have sought to pharmacologically differentiate NOD1 and TLR4 mediated signalling pathways in human endothelial cells, focussing on TAK1, NFκB and p38 MAPK. In addition we profile novel inhibitors of RIP2 and NOD1 itself, which specifically inhibit NOD1 ligand induced inflammatory signalling in the vasculature. This paper is the first to demonstrate activation of whole human artery by NOD1 stimulation and the relative importance of the endothelium in the sensing of NOD1 ligands by vessels. This data supports the potential utility of NOD1 and RIP2 as therapeutic targets in human disease where vascular inflammation is a clinical feature, such as in sepsis and septic shock.

  15. Lake sediment multi-taxon DNA from North Greenland records early post-glacial appearance of vascular plants and accurately tracks environmental changes

    DEFF Research Database (Denmark)

    Epp, L. S.; Gussarova, C.; Boessenkool, S.

    2015-01-01

    temperatures. Lake sediments contain DNA paleorecords of the surrounding ecosystems and can be used to retrieve a variety of organismal groups from a single sample. In this study, we analyzed vascular plant, bryophyte, algal (in particular diatom) and copepod DNA retrieved from a sediment core spanning...... phases, and distinct temporal changes in plant presence were recovered. The plant DNA was mostly in agreement with expected vegetation history, but very early occurrences of vascular plants, including the woody Empetrum nigrum, document terrestrial vegetation very shortly after glacial retreat. Our study...... core. Our DNA record was stratigraphically coherent, with no indication of leaching between layers, and our cross-taxon comparisons were in accordance with previously inferred local ecosystem changes. Authentic ancient plant DNA was retrieved from nearly all layers, both from the marine and the limnic...

  16. Feasibility of mesorectal vascular invasion in predicting early distant metastasis in patients with stage T3 rectal cancer based on rectal MRI

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young Chul; Kim, Jai Keun; Lee, Jei Hee [Ajou University School of Medicine, Department of Radiology, Suwon, Gyeonggi-do (Korea, Republic of); Kim, Myeong-Jin [Yonsei University Health system, Department of Diagnostic Radiology, Institute of Gastroenterology, Research Institute of Radiological Science, Seoul (Korea, Republic of); Kim, Young Bae [Ajou University School of Medicine, Department of Pathology, Suwon (Korea, Republic of); Shin, Sung Jae [Ajou University School of Medicine, Department of Gastroenterology, Suwon (Korea, Republic of)

    2016-02-15

    To evaluate the feasibility of mesorectal vascular invasion (MVI) in predicting early distant metastasis developed within 1 year of diagnosis of T3 rectal cancer using magnetic resonance imaging (MRI) Sixty-five patients with T3 rectal cancer (early metastasis, n = 28; non-metastasis, n = 37) were enrolled in this study. Early distant metastases developed in 28 patients (liver, n = 15; lung, n = 9; both, n = 4). Logistic regression was used to determine the independent predictors for early distant metastasis. In univariate analysis, tumour location, carcinoembryonic antigen (CEA), lymphovascular invasion (LVI), MRI-detected MVI, and mesorectal fat infiltration (MFI) (odds ratio [OR], 4.533, 9.583, 5.539, 27.046, and 5.539, respectively) were associated with early distant metastasis. Multivariate analysis demonstrated that MVI (OR, 29.949; P < 0.002) and LVI (OR, 6.684; P = 0.033) were independent factors for early distant metastasis. Specificity and positive predictive value (PPV) of MVI (94.59 %, and 89.47 %, respectively) were significantly higher than those of LVI (64.86 %, and 61.76 %), but sensitivity and negative predictive value were not significantly different between MVI (60.71 %, and 76.09 %) and LVI (75.00 %, and 77.42 %). While sensitivity of MRI-detected MVI was equal to that of CEA in predicting early distant metastasis from T3 rectal cancer, specificity and PPV may be improved by assessing MVI. (orig.)

  17. Mobilization of Circulating Vascular Progenitors in Cancer Patients Receiving External Beam Radiation in Response to Tissue Injury

    International Nuclear Information System (INIS)

    Allan, David S.; Morgan, Scott C.; Birch, Paul E.; Yang, Lin; Halpenny, Michael J.; Gunanayagam, Angelo; Li Yuhua; Eapen, Libni

    2009-01-01

    Purpose: Endothelial-like vascular progenitor cells (VPCs) are associated with the repair of ischemic tissue injury in several clinical settings. Because the endothelium is a principal target of radiation injury, VPCs may be important in limiting toxicity associated with radiotherapy (RT) in patients with cancer. Methods and Materials: We studied 30 patients undergoing RT for skin cancer (n = 5), head-and-neck cancer (n = 15), and prostate cancer (n = 10) prospectively, representing a wide range of irradiated mucosal volumes. Vascular progenitor cell levels were enumerated from peripheral blood at baseline, midway through RT, at the end of treatment, and 4 weeks after radiation. Acute toxicity was graded at each time point by use of the National Cancer Institute's Common Toxicity Criteria, version 3.0. Results: Significant increases in the proportion of CD34 + /CD133 + VPCs were observed after completion of RT, from 0.012% at baseline to 0.048% (p = 0.029), and the increase in this subpopulation was most marked in patients with Grade 2 peak toxicity or greater after RT (p = 0.034). Similarly, CD34 + /vascular endothelial growth factor receptor 2-positive VPCs were increased after the completion of radiation therapy in comparison to baseline (from 0.014% to 0.027%, p = 0.043), and there was a trend toward greater mobilization in patients with more significant toxicity (p = 0.08). The mobilization of CD34 + hematopoietic stem cells did not increase after treatment (p = 0.58), and there was no relationship with toxicity. Conclusions: We suggest that VPCs may play an important role in reducing radiation-induced tissue damage. Interventions that increase baseline VPC levels or enhance their mobilization and recruitment in response to RT may prove useful in facilitating more rapid and complete tissue healing.

  18. Early life adversity influences stress response association with smoking relapse.

    Science.gov (United States)

    al'Absi, Mustafa; Lemieux, Andrine; Westra, Ruth; Allen, Sharon

    2017-11-01

    We examined the hypothesis that stress-related blunting of cortisol in smokers is particularly pronounced in those with a history of severe life adversity. The two aims of this study were first to examine hormonal, craving, and withdrawal symptoms during ad libitum smoking and after the first 24 h of abstinence in smokers who experienced high or low levels of adversity. Second, we sought to examine the relationship between adversity and hypothalamic-pituitary-adrenal (HPA) hormones to predict relapse during the first month of a smoking cessation attempt. Hormonal and self-report measures were collected from 103 smokers (49 women) during ad libitum smoking and after the first 24 h of abstinence. HPA hormones were measured during baseline rest and in response to acute stress in both conditions. All smokers were interested in smoking cessation, and we prospectively used stress response measures to predict relapse during the first 4 weeks of the smoking cessation attempt. The results showed that high adversity was associated with higher distress and smoking withdrawal symptoms. High level of early life adversity was associated with elevated HPA activity, which was found in both salivary and plasma cortisol. Enhanced adrenocorticotropic hormone (ACTH) stress response was evident in high-adversity but not in low-adversity relapsers. This study demonstrated that early life adversity is associated with stress-related HPA responses. The study also demonstrated that, among smokers who experienced a high level of life adversity, heightened ACTH and cortisol responses were linked with increased risk for smoking relapse.

  19. Early-life inflammation, immune response and ageing.

    Science.gov (United States)

    Khan, Imroze; Agashe, Deepa; Rolff, Jens

    2017-03-15

    Age-related diseases are often attributed to immunopathology, which results in self-damage caused by an inappropriate inflammatory response. Immunopathology associated with early-life inflammation also appears to cause faster ageing, although we lack direct experimental evidence for this association. To understand the interactions between ageing, inflammation and immunopathology, we used the mealworm beetle Tenebrio molitor as a study organism. We hypothesized that phenoloxidase, an important immune effector in insect defence, may impose substantial immunopathological costs by causing tissue damage to Malpighian tubules (MTs; functionally equivalent to the human kidney), in turn accelerating ageing. In support of this hypothesis, we found that RNAi knockdown of phenoloxidase (PO) transcripts in young adults possibly reduced inflammation-induced autoreactive tissue damage to MTs, and increased adult lifespan. Our work thus suggests a causative link between immunopathological costs of early-life inflammation and faster ageing. We also reasoned that if natural selection weakens with age, older individuals should display increased immunopathological costs associated with an immune response. Indeed, we found that while old infected individuals cleared infection faster than young individuals, possibly they also displayed exacerbated immunopathological costs (larger decline in MT function) and higher post-infection mortality. RNAi-mediated knockdown of PO response partially rescued MTs function in older beetles and resulted in increased lifespan after infection. Taken together, our data are consistent with a direct role of immunopathological consequences of immune response during ageing in insects. Our work is also the first report that highlights the pervasive role of tissue damage under diverse contexts of ageing and immune response. © 2017 The Author(s).

  20. Early inflammatory response in rat brain after peripheral thermal injury.

    Science.gov (United States)

    Reyes, Raul; Wu, Yimin; Lai, Qin; Mrizek, Michael; Berger, Jamie; Jimenez, David F; Barone, Constance M; Ding, Yuchuan

    2006-10-16

    Previous studies have shown that the cerebral complications associated with skin burn victims are correlated with brain damage. The aim of this study was to determine whether systemic thermal injury induces inflammatory responses in the brain. Sprague Dawley rats (n=28) were studied in thermal injury and control groups. Animals from the thermal injury (n=14) and control (n=14) group were anesthetized and submerged to the neck vertically in 85 degrees C water for 6 s producing a third degree burn affecting 60-70% of the animal body surface area. The controls were submerged in 37 degrees C water for 6 s. Early expression of tumor necrosis factor-alpha (TNF-alpha), interleukin 1-beta (IL-1beta), and intracellular cell adhesion molecules (ICAM-1) protein levels in serum were determined at 3 (n=7) and 7 h (n=7) by enzyme-linked immunoabsorbent assay (ELISA). mRNA of TNF-alpha, IL-1beta, and ICAM-1 in the brain was measured at the same time points with a real-time reverse transcriptase-polymerase chain reaction (RT-PCR). An equal animal number was used for controls. Systemic inflammatory responses were demonstrated by dramatic up-regulations (5-50 fold) of TNF-alpha, IL-1beta, and ICAM-1 protein level in serum at 7 h after the thermal injury. However, as early as 3 h after peripheral thermal injury, a significant increase (3-15 fold) in mRNA expression of TNF-alpha, IL-1beta and ICAM-1 was observed in brain homogenates, with increased levels remaining at 7 h after injury. This study demonstrated an early inflammatory response in the brain after severe peripheral thermal injury. The cerebral inflammatory reaction was associated with expression of systemic cytokines and an adhesion molecule.

  1. Reproductive organ and vascular specific promoter of the rice plasma membrane Ca2+ATPase mediates environmental stress responses in plants.

    Science.gov (United States)

    Huda, Kazi Md Kamrul; Banu, Mst Sufara Akhter; Pathi, Krishna Mohan; Tuteja, Narendra

    2013-01-01

    Plasma membrane Ca(2+)ATPase is a transport protein in the plasma membrane of cells and helps in removal of calcium (Ca(2+)) from the cell, hence regulating Ca(2+) level within cells. Though plant Ca(2+)ATPases have been shown to be involved in plant stress responses but their promoter regions have not been well studied. The 1478 bp promoter sequence of rice plasma membrane Ca(2+)ATPase contains cis-acting elements responsive to stresses and plant hormones. To identify the functional region, serial deletions of the promoter were fused with the GUS sequence and four constructs were obtained. These were differentially activated under NaCl, PEG cold, methyl viologen, abscisic acid and methyl jasmonate treatments. We demonstrated that the rice plasma membrane Ca(2+)ATPase promoter is responsible for vascular-specific and multiple stress-inducible gene expression. Only full-length promoter showed specific GUS expression under stress conditions in floral parts. High GUS activity was observed in roots with all the promoter constructs. The -1478 to -886 bp flanking region responded well upon treatment with salt and drought. Only the full-length promoter presented cold-induced GUS expression in leaves, while in shoots slight expression was observed for -1210 and -886 bp flanking region. The -1210 bp deletion significantly responded to exogenous methyl viologen and abscisic acid induction. The -1210 and -886 bp flanking region resulted in increased GUS activity in leaves under methyl jasmonate treatments, whereas in shoots the -886 bp and -519 bp deletion gave higher expression. Salicylic acid failed to induce GUS activities in leaves for all the constructs. The rice plasma membrane Ca(2+)ATPase promoter is a reproductive organ-specific as well as vascular-specific. This promoter contains drought, salt, cold, methyl viologen, abscisic acid and methyl jasmonate related cis-elements, which regulated gene expression. Overall, the tissue-specificity and inducible nature of this

  2. Evasion of Early Antiviral Responses by Herpes Simplex Viruses

    Science.gov (United States)

    Suazo, Paula A.; Ibañez, Francisco J.; Retamal-Díaz, Angello R.; Paz-Fiblas, Marysol V.; Bueno, Susan M.; Kalergis, Alexis M.; González, Pablo A.

    2015-01-01

    Besides overcoming physical constraints, such as extreme temperatures, reduced humidity, elevated pressure, and natural predators, human pathogens further need to overcome an arsenal of antimicrobial components evolved by the host to limit infection, replication and optimally, reinfection. Herpes simplex virus-1 (HSV-1) and herpes simplex virus-2 (HSV-2) infect humans at a high frequency and persist within the host for life by establishing latency in neurons. To gain access to these cells, herpes simplex viruses (HSVs) must replicate and block immediate host antiviral responses elicited by epithelial cells and innate immune components early after infection. During these processes, infected and noninfected neighboring cells, as well as tissue-resident and patrolling immune cells, will sense viral components and cell-associated danger signals and secrete soluble mediators. While type-I interferons aim at limiting virus spread, cytokines and chemokines will modulate resident and incoming immune cells. In this paper, we discuss recent findings relative to the early steps taking place during HSV infection and replication. Further, we discuss how HSVs evade detection by host cells and the molecular mechanisms evolved by these viruses to circumvent early antiviral mechanisms, ultimately leading to neuron infection and the establishment of latency. PMID:25918478

  3. Histological responses of cutaneous vascular lesions following photodynamic therapy with talaporfin sodium: a chicken comb model.

    Science.gov (United States)

    Ohshiro, Takafumi; Nakajima, Tatsuo; Ogata, Hisao; Kishi, Kazuo

    2009-09-01

    Mono-L-aspartyl chlorin e6 (Talaporfin sodium) is a novel photosensitizer, and is currently being used in photodynamic therapy for various malignant tumors in combination with irradiation with a 664 nm laser. An interesting characteristic of Talaporfin sodium is that the skin photosensitivity after injection of this agent disappears faster than any other existing photosensitizers. This study examined the vascular events that occurred postirradiation in the chicken comb as a capillary malformation model after photosensitization with Talaporfin sodium. A single intravenous bolus injections of Talaporfin sodium was administered to the chickens, and a 1 cm diameter area of the comb of each animal was irradiated with a 664 nm visible red laser. The gross changes in the chicken combs were recorded for 7-14 days after photodynamic therapy. For the histological examination, HE, PTAH and Azan stained sections were analyzed. All treated chicken combs had blanched after photodynamic therapy. Microscopy demonstrated an absence of erythrocytes and the vessel lumina were obliterated, leaving the normal overlying epidermis completely intact. Concomitantly with selective destruction of the capillaries in the target area, moderate invasion of inflammatory cells and a slight increase in the stroma were observed. In the chicken comb model, photodynamic therapy with Talaporfin sodium effectively achieved selective destruction of the microvasculature while leaving the epidermis intact. Our results strongly suggest that photodynamic therapy with Talaporfin sodium could be a feasible method to treat dermal hypervascular lesions.

  4. Plasma-Sprayed Titanium Patterns for Enhancing Early Cell Responses

    Science.gov (United States)

    Shi, Yunqi; Xie, Youtao; Pan, Houhua; Zheng, Xuebin; Huang, Liping; Ji, Fang; Li, Kai

    2016-06-01

    Titanium coating has been widely used as a biocompatible metal in biomedical applications. However, the early cell responses and long-term fixation of titanium implants are not satisfied. To obviate these defects, in this paper, micro-post arrays with various widths (150-1000 μm) and intervals (100-300 μm) were fabricated on the titanium substrate by template-assisted plasma spraying technology. In vitro cell culture experiments showed that MC3T3-E1 cells exhibited significantly higher osteogenic differentiation as well as slightly improved adhesion and proliferation on the micro-patterned coatings compared with the traditional one. The cell number on the pattern with 1000 µm width reached 130% after 6 days of incubation, and the expressions of osteopontin (OPN) as well as osteocalcin (OC) were doubled. No obvious difference was found in cell adhesion on various size patterns. The present micro-patterned coatings proposed a new modification method for the traditional plasma spraying technology to enhance the early cell responses and convenience for the bone in-growth.

  5. Proteomic analysis of barley response during early spot blotch infection

    International Nuclear Information System (INIS)

    Al-Daoude, A.; Jawhar, M.; Shoaib, A.; Arabi, M.I.E.

    2015-01-01

    Spot blotch (SB), caused by the fungus Cochliobolus sativus, is a common foliar disease of barley worldwide, but little is known about the host response to infection at the protein level. In this study, a systematic shotgun proteomics approach was chosen to document the early barley response to C. sativus infection. Overall, 28 protein spots were consistently observed as differential in the proteome profiles of the challenged and unchallenged plants. After tryptic digestion, MALDI-TOF/MS analysis and MASCOT database searching identified proteins associated with the defense response including resistance proteins, putative hydrolase, proteinase, kinase and general metabolism and transport proteins. These afford important functions in host resistance and pathogen's inhibition in plants. One of the identified products is a putative NBS-LRR protein which is considered one of the major plant disease resistance proteins identified to date. This work indicates that, in combination with functional genomics, response of barley to challenge by C. sativus involved the recruitment of proteins from various defense pathways.(author)

  6. Α-Melanocyte-Stimulating Hormone Protects Early Diabetic Retina from Blood-Retinal Barrier Breakdown and Vascular Leakage via MC4R.

    Science.gov (United States)

    Cai, Siwei; Yang, Qianhui; Hou, Mengzhu; Han, Qian; Zhang, Hanyu; Wang, Jiantao; Qi, Chen; Bo, Qiyu; Ru, Yusha; Yang, Wei; Gu, Zhongxiu; Wei, Ruihua; Cao, Yunshan; Li, Xiaorong; Zhang, Yan

    2018-01-01

    Blood-retinal barrier (BRB) breakdown and vascular leakage is the leading cause of blindness of diabetic retinopathy (DR). Hyperglycemia-induced oxidative stress and inflammation are primary pathogenic factors of this severe DR complication. An effective interventional modality against the pathogenic factors during early DR is needed to curb BRB breakdown and vascular leakage. This study sought to examine the protective effects of α-Melanocyte-stimulating hormone (α-MSH) on early diabetic retina against vascular hyperpermeability, electrophysiological dysfunction, and morphological deterioration in a rat model of diabetes and probe the mechanisms underlying the α-MSH's anti-hyperpermeability in both rodent retinas and simian retinal vascular endothelial cells (RF6A). Sprague Dawley rats were injected through tail vein with streptozotocin to induce diabetes. The rats were intravitreally injected with α-MSH or saline at Week 1 and 3 after hyperglycemia. In another 2 weeks, Evans blue assay, transmission electron microscopy, electroretinogram (ERG), and hematoxylin and eosin (H&E) staining were performed to examine the protective effects of α-MSH in diabetic retinas. The expression of pro-inflammatory factors and tight junction at mRNA and protein levels in retinas was analyzed. Finally, the α-MSH's anti-hyperpermeability was confirmed in a high glucose (HG)-treated RF6A cell monolayer transwell culture by transendothelial electrical resistance (TEER) measurement and a fluorescein isothiocyanate-Dextran assay. Universal or specific melanocortin receptor (MCR) blockers were also employed to elucidate the MCR subtype mediating α-MSH's protection. Evans blue assay showed that BRB breakdown and vascular leakage was detected, and rescued by α-MSH both qualitatively and quantitatively in early diabetic retinas; electron microscopy revealed substantially improved retinal and choroidal vessel ultrastructures in α-MSH-treated diabetic retinas; scotopic ERG suggested

  7. Early transcriptional response of soybean contrasting accessions to root dehydration.

    Directory of Open Access Journals (Sweden)

    José Ribamar Costa Ferreira Neto

    Full Text Available Drought is a significant constraint to yield increase in soybean. The early perception of water deprivation is critical for recruitment of genes that promote plant tolerance. DeepSuperSAGE libraries, including one control and a bulk of six stress times imposed (from 25 to 150 min of root dehydration for drought-tolerant and sensitive soybean accessions, allowed to identify new molecular targets for drought tolerance. The survey uncovered 120,770 unique transcripts expressed by the contrasting accessions. Of these, 57,610 aligned with known cDNA sequences, allowing the annotation of 32,373 unitags. A total of 1,127 unitags were up-regulated only in the tolerant accession, whereas 1,557 were up-regulated in both as compared to their controls. An expression profile concerning the most representative Gene Ontology (GO categories for the tolerant accession revealed the expression "protein binding" as the most represented for "Molecular Function", whereas CDPK and CBL were the most up-regulated protein families in this category. Furthermore, particular genes expressed different isoforms according to the accession, showing the potential to operate in the distinction of physiological behaviors. Besides, heat maps comprising GO categories related to abiotic stress response and the unitags regulation observed in the expression contrasts covering tolerant and sensitive accessions, revealed the unitags potential for plant breeding. Candidate genes related to "hormone response" (LOX, ERF1b, XET, "water response" (PUB, BMY, "salt stress response" (WRKY, MYB and "oxidative stress response" (PER figured among the most promising molecular targets. Additionally, nine transcripts (HMGR, XET, WRKY20, RAP2-4, EREBP, NAC3, PER, GPX5 and BMY validated by RT-qPCR (four different time points confirmed their differential expression and pointed that already after 25 minutes a transcriptional reorganization started in response to the new condition, with important

  8. The CMV early enhancer/chicken beta actin (CAG) promoter can be used to drive transgene expression during the differentiation of murine embryonic stem cells into vascular progenitors

    DEFF Research Database (Denmark)

    Alexopoulou, Annika N; Couchman, John R; Whiteford, James

    2008-01-01

    BACKGROUND: Mouse embryonic stem cells cultured in vitro have the ability to differentiate into cells of the three germ layers as well as germ cells. The differentiation mimics early developmental events, including vasculogenesis and early angiogenesis and several differentiation systems are being...... used to identify factors that are important during the formation of the vascular system. Embryonic stem cells are difficult to transfect, while downregulation of promoter activity upon selection of stable transfectants has been reported, rendering the study of proteins by overexpression difficult....... RESULTS: CCE mouse embryonic stem cells were differentiated on collagen type IV for 4-5 days, Flk1+ mesodermal cells were sorted and replated either on collagen type IV in the presence of VEGFA to give rise to endothelial cells and smooth muscle cells or in collagen type I gels for the formation...

  9. Maternal circulating leukocytes display early chemotactic responsiveness during late gestation

    Directory of Open Access Journals (Sweden)

    Gomez-Lopez Nardhy

    2013-01-01

    Full Text Available Abstract Background Parturition has been widely described as an immunological response; however, it is unknown how this is triggered. We hypothesized that an early event in parturition is an increased responsiveness of peripheral leukocytes to chemotactic stimuli expressed by reproductive tissues, and this precedes expression of tissue chemotactic activity, uterine activation and the systemic progesterone/estradiol shift. Methods Tissues and blood were collected from pregnant Long-Evans rats on gestational days (GD 17, 20 and 22 (term gestation. We employed a validated Boyden chamber assay, flow cytometry, quantitative real time-polymerase chain reaction, and enzyme-linked immunosorbent assays. Results We found that GD20 maternal peripheral leukocytes migrated more than those from GD17 when these were tested with GD22 uterus and cervix extracts. Leukocytes on GD20 also displayed a significant increase in chemokine (C-C motif ligand 2 (Ccl2 gene expression and this correlated with an increase in peripheral granulocyte proportions and a decrease in B cell and monocyte proportions. Tissue chemotactic activity and specific chemokines (CCL2, chemokine (C-X-C motif ligand 1/CXCL1, and CXCL10 were mostly unchanged from GD17 to GD20 and increased only on GD22. CXCL10 peaked on GD20 in cervical tissues. As expected, prostaglandin F2α receptor and oxytocin receptor gene expression increased dramatically between GD20 and 22. Progesterone concentrations fell and estradiol-17β concentrations increased in peripheral serum, cervical and uterine tissue extracts between GD20 and 22. Conclusion Maternal circulating leukocytes display early chemotactic responsiveness, which leads to their infiltration into the uterus where they may participate in the process of parturition.

  10. Hyperhomocysteinaemia, vascular related pregnancy complications and the response to vitamin supplementation in pregnant women of Pakistan

    International Nuclear Information System (INIS)

    Qureshi, S.B.; Ahmad, M.; Qureshi, P.M.A.; Memon, A.; Qazi, R.A.

    2010-01-01

    To elaborate the relationship between serum homocysteine (hcy) levels and vascular related pregnancy complications in pregnant women as well as to assess the homocysteine lowering effects of folate, vitamin B12 and B6. The secondary objectives were to establish a link between serum homocysteine levels and maternal age, parity, gestational age, foetal birth weight, mean arterial pressure and albuminuria. Methods: A total of 332 pregnant women (gestational age: >24 weeks) attending Liaquat University Hospital Hyderabad, Pakistan, were enrolled. Of these 112 were healthy normal pregnant women; 61 pregnant women had pre-eclampsia, 49 with eclampsia and 110 with placental abruption. A cohort of 30 patients with elevated hcy levels (>8.2 mu mol/liter), were given folate, vitamin B12 and B6 as supplements for 6 weeks. Fasting blood samples were collected, centrifuged and stored at 2 to 8 deg. C. Hcy levels were determined by IMx immunoassay. Results: Higher serum hcy levels, higher mean arterial blood pressure (MAP), pre-term deliveries and low foetal birth weights were noted in women with pregnancies complicated by pre-eclampsia and eclampsia as compared to control and those with placental abruption. Significant hcy lowering effects of folate, vitamin B12 and B6 supplementation were observed. Significant and positive correlation was found between hhcy and MAP (r = 0.001; p<0.001), albuminuria (r = 0.004; p< 0.01) and low birth weights (r= 0.05; p<0.06). Conclusion: Higher hcy levels in pregnancies complicated by pre-eclampsia and eclampsia have been noted. Data support the hypothesis that folate, vitamin B12 and B6 lower hcy levels in hyperhomocysteinaemic women. (author)

  11. Early thrombus removal strategies for acute deep venous thrombosis: clinical practice guidelines of the Society for Vascular Surgery and the American Venous Forum.

    Science.gov (United States)

    Meissner, Mark H; Gloviczki, Peter; Comerota, Anthony J; Dalsing, Michael C; Eklof, Bo G; Gillespie, David L; Lohr, Joann M; McLafferty, Robert B; Murad, M Hassan; Padberg, Frank; Pappas, Peter; Raffetto, Joseph D; Wakefield, Thomas W

    2012-05-01

    The anticoagulant treatment of acute deep venous thrombosis (DVT) has been historically directed toward the prevention of recurrent venous thromboembolism. However, such treatment imperfectly protects against late manifestations of the postthrombotic syndrome. By restoring venous patency and preserving valvular function, early thrombus removal strategies can potentially decrease postthrombotic morbidity. A committee of experts in venous disease was charged by the Society for Vascular Surgery and the American Venous Forum to develop evidence-based practice guidelines for early thrombus removal strategies, including catheter-directed pharmacologic thrombolysis, pharmacomechanical thrombolysis, and surgical thrombectomy. Evidence-based recommendations are based on a systematic review and meta-analysis of the relevant literature, supplemented when necessary by less rigorous data. Recommendations are made according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, incorporating the strength of the recommendation (strong: 1; weak: 2) and an evaluation of the level of the evidence (A to C). On the basis of the best evidence currently available, we recommend against routine use of the term "proximal venous thrombosis" in favor of more precise characterization of thrombi as involving the iliofemoral or femoropopliteal venous segments (Grade 1A). We further suggest the use of early thrombus removal strategies in ambulatory patients with good functional capacity and a first episode of iliofemoral DVT of venous outflow obstruction (Grade 1A). We suggest pharmacomechanical strategies over catheter-directed pharmacologic thrombolysis alone if resources are available and that surgical thrombectomy be considered if thrombolytic therapy is contraindicated (Grade 2C). Most data regarding early thrombus removal strategies are of low quality but do suggest patient-important benefits with respect to reducing postthrombotic morbidity. We

  12. Dual channel photoplethysmography studies of cardio-vascular response to the body position changes

    Science.gov (United States)

    Erts, R.; Kukulis, I.; Spigulis, J.; Kere, L.

    2005-08-01

    The dual-channel photoplethysmography studies of physiological responses during 3-stage orthostatic test were performed. Clear differences in heartbeat rate, pulse wave transit time and blood pressure variations of healthy volunteers and diabetic patients have been observed.

  13. Enhancing early child care quality and learning for toddlers at risk: the responsive early childhood program.

    Science.gov (United States)

    Landry, Susan H; Zucker, Tricia A; Taylor, Heather B; Swank, Paul R; Williams, Jeffrey M; Assel, Michael; Crawford, April; Huang, Weihua; Clancy-Menchetti, Jeanine; Lonigan, Christopher J; Phillips, Beth M; Eisenberg, Nancy; Spinrad, Tracy L; de Villiers, Jill; de Villiers, Peter; Barnes, Marcia; Starkey, Prentice; Klein, Alice

    2014-02-01

    Despite reports of positive effects of high-quality child care, few experimental studies have examined the process of improving low-quality center-based care for toddler-age children. In this article, we report intervention effects on child care teachers' behaviors and children's social, emotional, behavioral, early literacy, language, and math outcomes as well as the teacher-child relationship. The intervention targeted the use of a set of responsive teacher practices, derived from attachment and sociocultural theories, and a comprehensive curriculum. Sixty-five childcare classrooms serving low-income 2- and 3-year-old children were randomized into 3 conditions: business-as-usual control, Responsive Early Childhood Curriculum (RECC), and RECC plus explicit social-emotional classroom activities (RECC+). Classroom observations showed greater gains for RECC and RECC+ teachers' responsive practices including helping children manage their behavior, establishing a predictable schedule, and use of cognitively stimulating activities (e.g., shared book reading) compared with controls; however, teacher behaviors did not differ for focal areas such as sensitivity and positive discipline supports. Child assessments demonstrated that children in the interventions outperformed controls in areas of social and emotional development, although children's performance in control and intervention groups was similar for cognitive skills (language, literacy, and math). Results support the positive impact of responsive teachers and environments providing appropriate support for toddlers' social and emotional development. Possible explanations for the absence of systematic differences in children's cognitive skills are considered, including implications for practice and future research targeting low-income toddlers.

  14. The cellular response to vascular endothelial growth factors requires co-ordinated signal transduction, trafficking and proteolysis.

    Science.gov (United States)

    Smith, Gina A; Fearnley, Gareth W; Tomlinson, Darren C; Harrison, Michael A; Ponnambalam, Sreenivasan

    2015-08-18

    VEGFs (vascular endothelial growth factors) are a family of conserved disulfide-linked soluble secretory glycoproteins found in higher eukaryotes. VEGFs mediate a wide range of responses in different tissues including metabolic homoeostasis, cell proliferation, migration and tubulogenesis. Such responses are initiated by VEGF binding to soluble and membrane-bound VEGFRs (VEGF receptor tyrosine kinases) and co-receptors. VEGF and receptor splice isoform diversity further enhances complexity of membrane protein assembly and function in signal transduction pathways that control multiple cellular responses. Different signal transduction pathways are simultaneously activated by VEGFR-VEGF complexes with membrane trafficking along the endosome-lysosome network further modulating signal output from multiple enzymatic events associated with such pathways. Balancing VEGFR-VEGF signal transduction with trafficking and proteolysis is essential in controlling the intensity and duration of different intracellular signalling events. Dysfunction in VEGF-regulated signal transduction is important in chronic disease states including cancer, atherosclerosis and blindness. This family of growth factors and receptors is an important model system for understanding human disease pathology and developing new therapeutics for treating such ailments. © 2015 Authors.

  15. In situ replacement of infected vascular prosthesis with fresh arterial homograft: Early and long-term results in 18 patients

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    Pejkić Siniša

    2013-01-01

    Full Text Available Introduction. Graft infection is rightly considered one of the severest complications of vascular reconstruction. Treatment is non­standardized and associated with high mortality and morbidity rates. The choice of therapeutic modality depends upon variety of factors. One increasingly used option is in situ replacement of the infected prosthesis with the arterial allograft. Objective. The aim of this prospective nonrandomized study was to evaluate the effectiveness and durability of fresh arterial allograft as in situ substitute for the infected vascular prosthesis. Methods. During period of 2002-2005, 18 patients with the synthetic vascular graft infection underwent partial or complete prosthesis removal and secondary in situ reconstruction using the fresh arterial allograft, preserved under hypothermic conditions in buffered saline solution with an addition of antibiotics. Results. In 14 male and 4 female patients, meanaged 62 years, 8 aortic and 10 peripheral arterial infected prostheses were partially or completely replaced with the allograft. Operative mortality was 27.8% and amputation rate was 22.2%. Systemic sepsis at initial presentation and highly virulent nature of causative microorganisms were identified as significant negative prognostic factors (χ² test, p<0.05. During the long­term follow­up (mean 47 months, allograft aneurysm developed in three patients, requiring allograft explantation, followed in two cases by tertiary prosthetic reconstruction. Conclusion. Substitution of the infected prosthesis with the arterial allograft could be successful if used selectively - for less virulent and localized infections of extracavitary grafts. Close follow­up is mandatory for timely diagnosis of late homograft lesions and its eventual replacement with more durable prosthetic material.

  16. Hyperoxia-Induced Proliferative Retinopathy: Early Interruption of Retinal Vascular Development with Severe and Irreversible Neurovascular Disruption.

    Directory of Open Access Journals (Sweden)

    Michelle Lajko

    Full Text Available Bronchopulmonary dysplasia (BPD is a major cause of neonatal morbidity in premature infants, occurring as a result of arrested lung development combined with multiple postnatal insults. Infants with BPD exposed to supplemental oxygen are at risk of retinopathy of prematurity as well. Thus, we studied the effects of hyperoxia on the retinal vasculature in a murine model of BPD. The retinal phenotype of this model, which we termed hyperoxia-induced proliferative retinopathy (HIPR, shows severe disruption of retinal vasculature and loss of vascular patterning, disorganized intra-retinal angiogenesis, inflammation and retinal detachment. Neonatal mice were subjected to 75% oxygen exposure from postnatal day (P0 to P14 to model BPD, then allowed to recover in room air for 1 (P15, 7 (P21, or 14 days (P28. We quantified retinal thickness, protein levels of HIF-1α, NOX2, and VEGF, and examined the cellular locations of these proteins by immunohistochemistry. We examined the retinal blood vessel integrity and inflammatory markers, including macrophages (F4/80 and lymphocytes (CD45R. Compared to controls, normal retinal vascular development was severely disrupted and replaced by a disorganized sheet of intra-retinal angiogenesis in the HIPR mice. At all time-points, HIPR showed persistent hyaloidal vasculature and a significantly thinner central retina compared to controls. HIF-1α protein levels were increased at P15, while VEGF levels continued to increase until P21. Intra-retinal fibrinogen was observed at P21 followed by sub-retinal deposition in at P28. Inflammatory lymphocytes and macrophages were observed at P21 and P28, respectively. This model presents a severe phenotype of disrupted retinal vascular development, intra-retinal angiogenesis inflammation and retinal detachment.

  17. Effects of age and caloric restriction in the vascular response of renal arteries to endothelin-1 in rats.

    Science.gov (United States)

    Amor, Sara; García-Villalón, Angel Luis; Rubio, Carmen; Carrascosa, Jose Ma; Monge, Luis; Fernández, Nuria; Martín-Carro, Beatriz; Granado, Miriam

    2017-02-01

    Cardiovascular alterations are the most prevalent cause of impaired physiological function in aged individuals with kidney being one the most affected organs. Aging-induced alterations in renal circulation are associated with a decrease in endothelium-derived relaxing factors such as nitric oxide (NO) and with an increase in contracting factors such as endothelin-1(ET-1). As caloric restriction (CR) exerts beneficial effects preventing some of the aging-induced alterations in cardiovascular system, the aim of this study was to analyze the effects of age and caloric restriction in the vascular response of renal arteries to ET-1 in aged rats. Vascular function was studied in renal arteries from 3-month-old Wistar rats fed ad libitum (3m) and in renal arteries from 8-and 24-month-old Wistar rats fed ad libitum (8m and 24m), or subjected to 20% caloric restriction during their three last months of life (8m-CR and 24m-CR). The contractile response to ET-1 was increased in renal arteries from 8m and 24m compared to 3m rats. ET-1-induced contraction was mediated by ET-A receptors in all experimental groups and also by ET-B receptors in 24m rats. Caloric restriction attenuated the increased contraction to ET-1 in renal arteries from 8m but not from 24m rats possibly through NO release proceeding from ET-B endothelial receptors. In 24m rats, CR did not attenuate the aging-increased response of renal arteries to ET-1, but it prevented the aging-induced increase in iNOS mRNA levels and the aging-induced decrease in eNOS mRNA levels in arterial tissue. In conclusion, aging is associated with an increased response to ET-1 in renal arteries that is prevented by CR in 8m but not in 24m rats. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Early inflammatory response in epithelial ovarian tumor cyst fluids

    International Nuclear Information System (INIS)

    Kristjánsdóttir, Björg; Partheen, Karolina; Fung, Eric T; Yip, Christine; Levan, Kristina; Sundfeldt, Karin

    2014-01-01

    Mortality rates for epithelial ovarian cancer (EOC) are high, mainly due to late-stage diagnosis. The identification of biomarkers for this cancer could contribute to earlier diagnosis and increased survival rates. Given that chronic inflammation plays a central role in cancer initiation and progression, we selected and tested 15 cancer-related cytokines and growth factors in 38 ovarian cyst fluid samples. We used ovarian cyst fluid since it is found in proximity to the pathology and mined it for inflammatory biomarkers suitable for early detection of EOC. Immunoprecipitation and high-throughput sample fractionation were obtained by using tandem antibody libraries bead and mass spectrometry. Two proteins, monocyte chemoattractant protein-1 (MCP-1/CCL2) and interleucin-8 (IL-8/CXCL8), were significantly (P < 0.0001) higher in the malignant (n = 16) versus benign (n = 22) tumor cysts. Validation of MCP-1, IL-8, and growth-regulated protein-α (GROα/CXCL1) was performed with ELISA in benign, borderline, and malignant cyst fluids (n = 256) and corresponding serum (n = 256). CA125 was measured in serum from all patients and used in the algorithms performed. MCP-1, IL-8, and GROα are proinflammatory cytokines and promoters of tumor growth. From 5- to 100-fold higher concentrations of MCP-1, IL-8 and GROα were detected in the cyst fluids compared to the serum. Significant (P < 0.001) cytokine response was already established in borderline cyst fluids and stage I EOC. In serum a significant (P < 0.01) increase of IL-8 and GROα was found, but not until stage I and stage III EOC, respectively. These findings confirm that early events in tumorigenesis can be analyzed and detected in the tumor environment and we conclude that ovarian cyst fluid is a promising source in the search for new biomarkers for early ovarian tumors

  19. The vascular disrupting agent ZD6126 shows increased antitumor efficacy and enhanced radiation response in large, advanced tumors

    International Nuclear Information System (INIS)

    Siemann, Dietmar W.; Rojiani, Amyn M.

    2005-01-01

    Purpose: ZD6126 is a vascular-targeting agent that induces selective effects on the morphology of proliferating and immature endothelial cells by disrupting the tubulin cytoskeleton. The efficacy of ZD6126 was investigated in large vs. small tumors in a variety of animal models. Methods and Materials: Three rodent tumor models (KHT, SCCVII, RIF-1) and three human tumor xenografts (Caki-1, KSY-1, SKBR3) were used. Mice bearing leg tumors ranging in size from 0.1-2.0 g were injected intraperitoneally with a single 150 mg/kg dose of ZD6126. The response was assessed by morphologic and morphometric means as well as an in vivo to in vitro clonogenic cell survival assay. To examine the impact of tumor size on the extent of enhancement of radiation efficacy by ZD6126, KHT sarcomas of three different sizes were irradiated locally with a range of radiation doses, and cell survival was determined. Results: All rodent tumors and human tumor xenografts evaluated showed a strong correlation between increasing tumor size and treatment effect as determined by clonogenic cell survival. Detailed evaluation of KHT sarcomas treated with ZD6126 showed a reduction in patent tumor blood vessels that was ∼20% in small ( 90% in large (>1.0 g) tumors. Histologic assessment revealed that the extent of tumor necrosis after ZD6126 treatment, although minimal in small KHT sarcomas, became more extensive with increasing tumor size. Clonogenic cell survival after ZD6126 exposure showed a decrease in tumor surviving fraction from approximately 3 x 10 -1 to 1 x 10 -4 with increasing tumor size. When combined with radiotherapy, ZD6126 treatment resulted in little enhancement of the antitumor effect of radiation in small (<0.3 g) tumors but marked increases in cell kill in tumors larger than 1.0 g. Conclusions: Because bulky neoplastic disease is typically the most difficult to manage, the present findings provide further support for the continued development of vascular disrupting agents such as

  20. Vascular endothelium as a target of immune response in renal transplant rejection

    Directory of Open Access Journals (Sweden)

    Giovanni ePiotti

    2014-10-01

    Full Text Available This review of clinical and experimental studies aims at analysing the interplay between graft endothelium and host immune system in renal transplantation, and how it affects the survival of the graft. Graft endothelium is indeed the first barrier between self and non-self that is encountered by host lymphocytes upon reperfusion of vascularised solid transplants. Endothelial cells express all the major sets of antigens that elicit host immune response, and therefore represent a preferential target in organ rejection.Some of the antigens expressed by endothelial cells are target of the antibody-mediated response, such as the AB0 blood group system, the HLA and MICA systems, and the endothelial cell-restricted antigens; for each of these systems, the mechanisms of interaction and damage of both preformed and de novo donor-specific antibodies are reviewed along with their impact on renal graft survival. Moreover the rejection process can force injured endothelial cells to expose cryptic self-antigens, toward which an auto-immune response mounts, overlapping to the allo-immune response in the damaging of the graft. Not only are endothelial cells a passive target of the host immune response, but also an active player in lymphocyte activation; therefore their interaction with allogenic T-cells is analysed on the basis of experimental in vitro and in vivo studies, according to the patterns of expression of the HLA class I and II and the co-stimulatory molecules specific for cytotoxic and helper T-cells.Finally, as the response that follows transplantation has proven to be not necessarily destructive, the factors that foster graft endothelium functioning in spite of rejection, and how they could be therapeutically harnessed to promote long-term graft acceptance, are described: accommodation that is resistance of endothelial cells to donor-specific antibodies, and endothelial cell ability to induce Foxp3+ Regulatory T-cells, that are crucial mediators of

  1. Matrix Metalloproteinase-2 Activity is Associated with Divergent Regulation of Calponin-1 in Conductance and Resistance Arteries in Hypertension-induced Early Vascular Dysfunction and Remodelling.

    Science.gov (United States)

    Parente, Juliana M; Pereira, Camila A; Oliveira-Paula, Gustavo H; Tanus-Santos, José E; Tostes, Rita C; Castro, Michele M

    2017-10-01

    Matrix metalloproteinase (MMP)-2 participates in hypertension-induced maladaptive vascular remodelling by degrading extra- and intracellular proteins. The consequent extracellular matrix rearrangement and phenotype switch of vascular smooth muscle cells (VSMCs) lead to increased cellular migration and proliferation. As calponin-1 degradation by MMP-2 may lead to VSMC proliferation during hypertension, the hypothesis of this study is that increased MMP-2 activity contributes to early hypertension-induced maladaptive remodelling in conductance and resistance arteries via regulation of calponin-1. The main objective was to analyse whether MMP-2 exerts similar effects on the structure and function of the resistance and conductance arteries during early hypertension. Two-kidney, one-clip (2K-1C) hypertensive male rats and corresponding controls were treated with doxycycline (30 mg/kg/day) or water until reaching one week of hypertension. Systolic blood pressure was increased in 2K-1C rats, and doxycycline did not reduce it. Aortas and mesenteric arteries were analysed. MMP-2 activity and expression were increased in both arteries, and doxycycline reduced it. Significant hypertrophic remodelling and VSMC proliferation were observed in aortas but not in mesenteric arteries of 2K-1C rats. The contractility of mesenteric arteries to phenylephrine was increased in 2K-1C rats, and doxycycline prevented this alteration. The potency of phenylephrine to contract aortas of 2K-1C rats was increased, and doxycycline decreased it. Whereas calponin-1 expression was increased in 2K-1C mesenteric arteries, calponin-1 was reduced in aortas. Doxycycline treatment reverted changes in calponin-1 expression. MMP-2 contributes to hypertrophic remodelling in aortas by decreasing calponin-1 levels, which may result in VSMC proliferation. On the other hand, MMP-2-dependent increased calponin-1 in mesenteric arteries may contribute to vascular hypercontractility in 2K-1C rats. Divergent

  2. Liver CT for vascular mapping during radioembolisation workup : comparison of an early and late arterial phase protocol

    NARCIS (Netherlands)

    van den Hoven, Andor F; Braat, Manon N G J A; Prince, Jip F; van Doormaal, Pieter J; van Leeuwen, Maarten S; Lam, Marnix G E H; van den Bosch, Maurice A A J

    OBJECTIVES: To compare right gastric (RGA) and segment 4 artery (A4) origin detection rates during radioembolisation workup between early and late arterial phase liver CT protocols. METHODS: 100 consecutive patients who underwent liver CT between May 2012-January 2015 with early or late arterial

  3. Human cutaneous vascular responses to whole-body tilting, Gz centrifugation, and LBNP

    Science.gov (United States)

    Watenpaugh, Donald E.; Breit, Gregory A.; Buckley, Theresa M.; Ballard, Richard E.; Murthy, Gita; Hargens, Alan R.

    2004-01-01

    We hypothesized that gravitational stimuli elicit cardiovascular responses in the following order with gravitational stress equalized at the level of the feet, from lowest to highest response: short-(SAC) and long-arm centrifugation (LAC), tilt, and lower body negative pressure (LBNP). Up to 15 healthy subjects underwent graded application of the four stimuli. Laser-Doppler flowmetry measured regional skin blood flow. At 0.6 G(z) (60 mmHg LBNP), tilt and LBNP similarly reduced leg skin blood flow to approximately 36% of supine baseline levels. Flow increased back toward baseline levels at 80-100 mmHg LBNP yet remained stable during 0.8-1.0 G(z) tilt. Centrifugation usually produced less leg vasoconstriction than tilt or LBNP. Surprisingly, SAC and LAC did not differ significantly. Thigh responses were less definitive than leg responses. No gravitational vasoconstriction occurred in the neck. All conditions except SAC increased heart rate, according to our hypothesized order. LBNP may be a more effective and practical means of simulating cardiovascular effects of gravity than centrifugation.

  4. Assessment of Liver Remnant Using ICG Clearance Intraoperatively during Vascular Exclusion: Early Experience with the ALIIVE Technique

    Directory of Open Access Journals (Sweden)

    Lawrence Lau

    2015-01-01

    Full Text Available Background. The most significant risk following major hepatectomy is postoperative liver insufficiency. Current preoperative assessment of the future liver remnant relies upon assumptions which may not be valid in the setting of advanced resection strategies. This paper reports the feasibility of the ALIIVE technique which assesses the liver remnant with ICG clearance intraoperatively during vascular exclusion. Methods. 10 patients undergoing planned major liver resection (hemihepatectomy or greater were recruited. Routine preoperative assessment included CT and standardized volumetry. ICG clearance was measured noninvasively using a finger spectrophotometer at various time points including following parenchymal transection during inflow and outflow occlusion before vascular division, the ALIIVE step. Results. There were one case of mortality and three cases of posthepatectomy liver failure. The patient who died had the lowest ALIIVE ICG clearance (7.1%/min versus 14.4 ± 4.9. Routine preoperative CT and standardized volumetry did not predict outcome. Discussion/Conclusion. The novel ALIIVE technique is feasible and assesses actual future liver remnant function before the point of no return during major hepatectomy. This technique may be useful as a check step to offer a margin of safety to prevent posthepatectomy liver failure and death. Further confirmatory studies are required to determine a safety cutoff level.

  5. Reproductive organ and vascular specific promoter of the rice plasma membrane Ca2+ATPase mediates environmental stress responses in plants.

    Directory of Open Access Journals (Sweden)

    Kazi Md Kamrul Huda

    Full Text Available Plasma membrane Ca(2+ATPase is a transport protein in the plasma membrane of cells and helps in removal of calcium (Ca(2+ from the cell, hence regulating Ca(2+ level within cells. Though plant Ca(2+ATPases have been shown to be involved in plant stress responses but their promoter regions have not been well studied.The 1478 bp promoter sequence of rice plasma membrane Ca(2+ATPase contains cis-acting elements responsive to stresses and plant hormones. To identify the functional region, serial deletions of the promoter were fused with the GUS sequence and four constructs were obtained. These were differentially activated under NaCl, PEG cold, methyl viologen, abscisic acid and methyl jasmonate treatments. We demonstrated that the rice plasma membrane Ca(2+ATPase promoter is responsible for vascular-specific and multiple stress-inducible gene expression. Only full-length promoter showed specific GUS expression under stress conditions in floral parts. High GUS activity was observed in roots with all the promoter constructs. The -1478 to -886 bp flanking region responded well upon treatment with salt and drought. Only the full-length promoter presented cold-induced GUS expression in leaves, while in shoots slight expression was observed for -1210 and -886 bp flanking region. The -1210 bp deletion significantly responded to exogenous methyl viologen and abscisic acid induction. The -1210 and -886 bp flanking region resulted in increased GUS activity in leaves under methyl jasmonate treatments, whereas in shoots the -886 bp and -519 bp deletion gave higher expression. Salicylic acid failed to induce GUS activities in leaves for all the constructs.The rice plasma membrane Ca(2+ATPase promoter is a reproductive organ-specific as well as vascular-specific. This promoter contains drought, salt, cold, methyl viologen, abscisic acid and methyl jasmonate related cis-elements, which regulated gene expression. Overall, the tissue-specificity and inducible

  6. Monitoring early tumor response to drug therapy with diffuse optical tomography

    Science.gov (United States)

    Flexman, Molly L.; Vlachos, Fotios; Kim, Hyun Keol; Sirsi, Shashank R.; Huang, Jianzhong; Hernandez, Sonia L.; Johung, Tessa B.; Gander, Jeffrey W.; Reichstein, Ari R.; Lampl, Brooke S.; Wang, Antai; Borden, Mark A.; Yamashiro, Darrell J.; Kandel, Jessica J.; Hielscher, Andreas H.

    2012-01-01

    Although anti-angiogenic agents have shown promise as cancer therapeutics, their efficacy varies between tumor types and individual patients. Providing patient-specific metrics through rapid noninvasive imaging can help tailor drug treatment by optimizing dosages, timing of drug cycles, and duration of therapy--thereby reducing toxicity and cost and improving patient outcome. Diffuse optical tomography (DOT) is a noninvasive three-dimensional imaging modality that has been shown to capture physiologic changes in tumors through visualization of oxygenated, deoxygenated, and total hemoglobin concentrations, using non-ionizing radiation with near-infrared light. We employed a small animal model to ascertain if tumor response to bevacizumab (BV), an anti-angiogenic agent that targets vascular endothelial growth factor (VEGF), could be detected at early time points using DOT. We detected a significant decrease in total hemoglobin levels as soon as one day after BV treatment in responder xenograft tumors (SK-NEP-1), but not in SK-NEP-1 control tumors or in non-responder control or BV-treated NGP tumors. These results are confirmed by magnetic resonance imaging T2 relaxometry and lectin perfusion studies. Noninvasive DOT imaging may allow for earlier and more effective control of anti-angiogenic therapy.

  7. Early response to therapy and survival in multiple myeloma.

    Science.gov (United States)

    Schaar, C G; Kluin-Nelemans, J C; le Cessie, S; Franck, P F H; te Marvelde, M C; Wijermans, P W

    2004-04-01

    Whether the response to chemotherapy is a prognosticator in multiple myeloma (MM) is still not known. Therefore, the relationship between survival and the rate of monoclonal protein (M-protein) decrement during the first cycles of therapy was prospectively assessed in 262 patients with newly diagnosed MM that were included in a phase III trial (HOVON-16). M-proteins were collected monthly during melphalan-prednisone therapy (MP: melphalan 0.25 mg/kg, prednisone 1.0 mg/kg orally for 5 d every 4 weeks). Patients with light chain disease (n = 18), immunoglobulin M (IgM)-MM (n = 1) and no immunotyping (n = 1) were excluded. Of the 242 patients studied, 75% had IgG M-protein and 25% IgA; MM stages: I: 1%, II: 35% and III: 64%. The median M-protein decrease after the first cycle of MP was 21% for IgG and 27% for IgA, and declined to < 5% after four cycles. An obvious survival advantage was seen for patients who had an M-protein decrease of at least 30% after the first MP cycle, which became significant when an M-protein decrease of 40% or more was reached. As established prognostic parameters (Salmon & Durie stage, serum creatinine, and haemoglobin) also remained prognostically significant, we concluded that early response to MP predicts for survival in MM.

  8. Effect of airway acidosis and alkalosis on airway vascular smooth muscle responsiveness to albuterol.

    Science.gov (United States)

    Cancado, Jose E; Mendes, Eliana S; Arana, Johana; Horvath, Gabor; Monzon, Maria E; Salathe, Matthias; Wanner, Adam

    2015-04-02

    In vitro and animal experiments have shown that the transport and signaling of β2-adrenergic agonists are pH-sensitive. Inhaled albuterol, a hydrophilic β2-adrenergic agonist, is widely used for the treatment of obstructive airway diseases. Acute exacerbations of obstructive airway diseases can be associated with changes in ventilation leading to either respiratory acidosis or alkalosis thereby affecting albuterol responsiveness in the airway. The purpose of this study was to determine if airway pH has an effect on albuterol-induced vasodilation in the airway. Ten healthy volunteers performed the following respiratory maneuvers: quiet breathing, hypocapnic hyperventilation, hypercapnic hyperventilation, and eucapnic hyperventilation (to dissociate the effect of pH from the effect of ventilation). During these breathing maneuvers, exhaled breath condensate (EBC) pH and airway blood flow response to inhaled albuterol (ΔQ̇aw) were assessed. Mean ± SE EBC pH (units) and ΔQ̇aw (μl.min(-1).mL(-1)) were 6.4 ± 0.1 and 16.8 ± 1.9 during quiet breathing, 6.3 ± 0.1 and 14.5 ± 2.4 during eucapnic hyperventilation, 6.6 ± 0.2 and -0.2 ± 1.8 during hypocapnic hyperventilation (p = 0.02 and <0.01 vs. quiet breathing), and 5.9 ± 0.1 and 2.0 ± 1.5 during hypercapnic hyperventilation (p = 0.02 and <0.02 vs quiet breathing). Albuterol responsiveness in the airway as assessed by ΔQ̇aw is pH sensitive. The breathing maneuver associated with decreased and increased EBC pH both resulted in a decreased responsiveness independent of the level of ventilation. These findings suggest an attenuated response to hydrophilic β2-adrenergic agonists during airway disease exacerbations associated with changes in pH. Registered at clinicaltrials.gov: NCT01216748 .

  9. Co-ordination of physiological and morphological responses of stomata to elevated [CO2] in vascular plants.

    Science.gov (United States)

    Haworth, Matthew; Elliott-Kingston, Caroline; McElwain, Jennifer C

    2013-01-01

    Plant stomata display a wide range of short-term behavioural and long-term morphological responses to atmospheric carbon dioxide concentration ([CO(2)]). The diversity of responses suggests that plants may have different strategies for controlling gas exchange, yet it is not known whether these strategies are co-ordinated in some way. Here, we test the hypothesis that there is co-ordination of physiological (via aperture change) and morphological (via stomatal density change) control of gas exchange by plants. We examined the response of stomatal conductance (G(s)) to instantaneous changes in external [CO(2)] (C(a)) in an evolutionary cross-section of vascular plants grown in atmospheres of elevated [CO(2)] (1,500 ppm) and sub-ambient [O(2)] (13.0 %) compared to control conditions (380 ppm CO(2), 20.9 % O(2)). We found that active control of stomatal aperture to [CO(2)] above current ambient levels was not restricted to angiosperms, occurring in the gymnosperms Lepidozamia peroffskyana and Nageia nagi. The angiosperm species analysed appeared to possess a greater respiratory demand for stomatal movement than gymnosperm species displaying active stomatal control. Those species with little or no control of stomatal aperture (termed passive) to C(a) were more likely to exhibit a reduction in stomatal density than species with active stomatal control when grown in atmospheres of elevated [CO(2)]. The relationship between the degree of stomatal aperture control to C(a) above ambient and the extent of any reduction in stomatal density may suggest the co-ordination of physiological and morphological responses of stomata to [CO(2)] in the optimisation of water use efficiency. This trade-off between stomatal control strategies may have developed due to selective pressures exerted by the costs associated with passive and active stomatal control.

  10. Retinal Vascular and Oxygen Temporal Dynamic Responses to Light Flicker in Humans.

    Science.gov (United States)

    Felder, Anthony E; Wanek, Justin; Blair, Norman P; Shahidi, Mahnaz

    2017-11-01

    To mathematically model the temporal dynamic responses of retinal vessel diameter (D), oxygen saturation (SO2), and inner retinal oxygen extraction fraction (OEF) to light flicker and to describe their responses to its cessation in humans. In 16 healthy subjects (age: 60 ± 12 years), retinal oximetry was performed before, during, and after light flicker stimulation. At each time point, five metrics were measured: retinal arterial and venous D (DA, DV) and SO2 (SO2A, SO2V), and OEF. Intra- and intersubject variability of metrics was assessed by coefficient of variation of measurements before flicker within and among subjects, respectively. Metrics during flicker were modeled by exponential functions to determine the flicker-induced steady state metric values and the time constants of changes. Metrics after the cessation of flicker were compared to those before flicker. Intra- and intersubject variability for all metrics were less than 6% and 16%, respectively. At the flicker-induced steady state, DA and DV increased by 5%, SO2V increased by 7%, and OEF decreased by 13%. The time constants of DA and DV (14, 15 seconds) were twofold smaller than those of SO2V and OEF (39, 34 seconds). Within 26 seconds after the cessation of flicker, all metrics were not significantly different from before flicker values (P ≥ 0.07). Mathematical modeling revealed considerable differences in the time courses of changes among metrics during flicker, indicating flicker duration should be considered separately for each metric. Future application of this method may be useful to elucidate alterations in temporal dynamic responses to light flicker due to retinal diseases.

  11. Identification of chemical components of combustion emissions that affect pro-atherosclerotic vascular responses in mice

    OpenAIRE

    Seilkop, Steven K.; Campen, Matthew J.; Lund, Amie K.; McDonald, Jacob D.; Mauderly, Joe L.

    2012-01-01

    Combustion emissions cause pro-atherosclerotic responses in apolipoprotein E-deficient (ApoE/−) mice, but the causal components of these complex mixtures are unresolved. In studies previously reported, ApoE−/− mice were exposed by inhalation 6 h/day for 50 consecutive days to multiple dilutions of diesel or gasoline exhaust, wood smoke, or simulated “downwind” coal emissions. In this study, the analysis of the combined four-study database using the Multiple Additive Regression Trees (MART) da...

  12. Short-term sensory and cutaneous vascular responses to therapeutic ultrasound in the forearms of healthy volunteers.

    Science.gov (United States)

    Shaik, Shaguftha Sultana; MacDermid, Joy C; Birmingham, Trevor; Grewal, Ruby; Farooq, Baseer

    2014-01-01

    Therapeutic ultrasound (US) is used for a variety of clinical pathologies and is thought to accelerate tissue repair and help with pain reduction via its thermal and nonthermal effects. The evidence on physiological effects of US on both sensory and vascular functions in humans is incomplete. Hence, the purpose of this study was to determine the short-term impact of two doses of US (3 MHz, 1:4, 0.25 W/cm(2), 5 min; 1 MHz, continuous, 0.8 W/cm(2), 3 min), on sensory and vascular responses in the healthy forearms. Twenty healthy subjects were recruited (mean age, 29.6 ± 8.8 years) for the study. Superficial blood flow (SBF) in the distal forearms was determined using the tissue viability imaging system. Sensory perception thresholds (SPT) were determined from ring finger (C7, C8) to assess A-beta (at 2,000 Hz) and C fiber function (at 5 Hz), using a Neurometer CPT/C device. Subject's two hands were randomly allocated to group order (AB/BA). Scores were obtained before and immediately after the application of US and control. Differences in these were analyzed using repeated measures. Both 3 MHz pulsed US and 1 MHz continuous US showed small to moderate (effect size = 0.12 to 0.68), statistically significant reductions in SBF (3 MHz, mean change = 2.8 AU and 1 MHz, mean change = 3.9 AU, p 0.05). Age and gender also had no effect on all outcome measures (p > 0.05). This study demonstrated minor reductions in skin blood flow, skin temperatures, and C fiber perception thresholds immediately after 3 MHz, and 1 MHz US. The responses observed may have been due to a thermo-cooling effect of the gel or due to the direct effect of US on C fibers of median and ulnar nerves. US had a negligible effect on A-beta fibres. This would suggest that future studies looking at physiological effects of US should move towards investigating larger dosages and study the effects in patient populations.

  13. Human-derived nanoparticles and vascular response to injury in rabbit carotid arteries: Proof of principle

    Directory of Open Access Journals (Sweden)

    Maria A K Schwartz

    2008-06-01

    Full Text Available Maria A K Schwartz1, John C Lieske2, Vivek Kumar2, Gerard Farell-Baril2, Virginia M Miller1,31Departments of Physiology and Biomedical Engineering, Internal Medicine; 2Division of Nephrology, and 3Surgery, Mayo Clinic College of Medicine, Rochester, MN, USAAbstract: Self-calcifying, self-replicating nanoparticles have been isolated from calcified human tissues. However, it is unclear if these nanoparticles participate in disease processes. Therefore, this study was designed to preliminarily test the hypothesis that human-derived nanoparticles are causal to arterial disease processes. One carotid artery of 3 kg male rabbits was denuded of endothelium; the contralateral artery remained unoperated as a control. Each rabbit was injected intravenously with either saline, calcified, or decalcified nanoparticles cultured from calcified human arteries or kidney stones. After 35 days, both injured and control arteries were removed for histological examination. Injured arteries from rabbits injected with saline showed minimal, eccentric intimal hyperplasia. Injured arteries from rabbits injected with calcified kidney stone- and arterial-derived nanoparticles occluded, sometimes with canalization. The calcified kidney stone-derived nanoparticles caused calcifications within the occlusion. Responses to injury in rabbits injected with decalcified kidney stone-derived nanoparticles were similar to those observed in saline-injected animals. However, decalcified arterial-derived nanoparticles produced intimal hyperplasia that varied from moderate to occlusion with canalization and calcifi cation. This study offers the first evidence that there may be a causal relationship between human-derived nanoparticles and response to injury including calcification in arteries with damaged endothelium.Keywords: arterial calcification, endothelial injury, intimal hyperplasia

  14. The effect of ethnicity on the vascular responses to cold exposure of the extremities.

    Science.gov (United States)

    Maley, Matthew J; Eglin, Clare M; House, James R; Tipton, Michael J

    2014-11-01

    Cold injuries are more prevalent in individuals of African descent (AFD). Therefore, we investigated the effect of extremity cooling on skin blood flow (SkBF) and temperature (T sk) between ethnic groups. Thirty males [10 Caucasian (CAU), 10 Asian (ASN), 10 AFD] undertook three tests in 30 °C air whilst digit T sk and SkBF were measured: (i) vasomotor threshold (VT) test--arm immersed in 35 °C water progressively cooled to 10 °C and rewarmed to 35 °C to identify vasoconstriction and vasodilatation; (ii) cold-induced vasodilatation (CIVD) test--hand immersed in 8 °C water for 30 min followed by spontaneous warming; (iii) cold sensitivity (CS) test--foot immersed in 15 °C water for 2 min followed by spontaneous warming. Cold sensory thresholds of the forearm and finger were also assessed. In the VT test, vasoconstriction and vasodilatation occurred at a warmer finger T sk in AFD during cooling [21.2 (4.4) vs. 17.0 (3.1) °C, P = 0.034] and warming [22.0 (7.9) vs. 12.1 (4.1) °C, P = 0.002] compared with CAU. In the CIVD test, average SkBF during immersion was greater in CAU [42 (24) %] than ASN [25 (8) %, P = 0.036] and AFD [24 (13) %, P = 0.023]. Following immersion, SkBF was higher and rewarming faster in CAU [3.2 (0.4) °C min(-1)] compared with AFD [2.5 (0.7) °C min(-1), P = 0.037], but neither group differed from ASN [3.0 (0.6) °C min(-1)]. Responses to the CS test and cold sensory thresholds were similar between groups. AFD experienced a more intense protracted finger vasoconstriction than CAU during hand immersion, whilst ASN experienced an intermediate response. This greater sensitivity to cold may explain why AFD are more susceptible to cold injuries.

  15. Language experience enhances early cortical pitch-dependent responses

    Science.gov (United States)

    Krishnan, Ananthanarayan; Gandour, Jackson T.; Ananthakrishnan, Saradha; Vijayaraghavan, Venkatakrishnan

    2014-01-01

    Pitch processing at cortical and subcortical stages of processing is shaped by language experience. We recently demonstrated that specific components of the cortical pitch response (CPR) index the more rapidly-changing portions of the high rising Tone 2 of Mandarin Chinese, in addition to marking pitch onset and sound offset. In this study, we examine how language experience (Mandarin vs. English) shapes the processing of different temporal attributes of pitch reflected in the CPR components using stimuli representative of within-category variants of Tone 2. Results showed that the magnitude of CPR components (Na-Pb and Pb-Nb) and the correlation between these two components and pitch acceleration were stronger for the Chinese listeners compared to English listeners for stimuli that fell within the range of Tone 2 citation forms. Discriminant function analysis revealed that the Na-Pb component was more than twice as important as Pb-Nb in grouping listeners by language affiliation. In addition, a stronger stimulus-dependent, rightward asymmetry was observed for the Chinese group at the temporal, but not frontal, electrode sites. This finding may reflect selective recruitment of experience-dependent, pitch-specific mechanisms in right auditory cortex to extract more complex, time-varying pitch patterns. Taken together, these findings suggest that long-term language experience shapes early sensory level processing of pitch in the auditory cortex, and that the sensitivity of the CPR may vary depending on the relative linguistic importance of specific temporal attributes of dynamic pitch. PMID:25506127

  16. Depressão vascular no idoso: resposta ao tratamento antidepressivo associado a inibidor das colinesterases Vascular depression in elderly: response to treatment with antidepressant associated to cholinesterase inhibitor

    Directory of Open Access Journals (Sweden)

    Ricardo Barcelos

    2007-01-01

    Full Text Available CONTEXTO: Entre os transtornos neuropsiquiátricos ocasionados por eventos cerebrovasculares, a depressão vascular é pouco diagnosticada por médicos não especialistas, causando aumento da morbimortalidade de pacientes idosos. CASO CLÍNICO: Trata-se de um paciente com 67 anos que apresentou resposta parcial a tratamento com inibidores da recaptura de serotonina e efeitos adversos autonômicos graves com outros antidepressivos. A adição de rivastigmina ao citalopram promoveu sucesso terapêutico, com redução de 23 para 7 pontos, na escala de Hamilton para depressão. DISCUSSÃO: O resultado obtido traz novas perspectivas para o tratamento da depressão vascular, sendo necessários ensaios clínicos controlados que evidenciem o benefício da adição dos inibidores das colinesterases aos antidepressivos no tratamento destes pacientes.CONTEXT: Among neuropsychiatric disorders caused by cerebrovascular factors, vascular depression is diagnosed in a small degree by general practitioners, causing morbid-mortality increase in elderly. CASE REPORT: That is a case of a 67 year-old-man with partial response after treatment with a Selective Serotonin Receptors Inhibitor, and severe autonomic adverse effects with other antidepressants. The addition of rivastigmine to citalopram resulted in a therapeutic success, with a reduction of 23 to 7 points on the Hamilton Depressive Scale (HAM-D. DISCUSSION: The result obtained brings new perspectives to the treatment of vascular depression, providing that randomized controlled trials with larger sample sizes confirm the positive effect of the addition of a cholinesterase inhibitor to antidepressants in the treatment of these patients.

  17. Liver CT for vascular mapping during radioembolisation workup: comparison of an early and late arterial phase protocol

    Energy Technology Data Exchange (ETDEWEB)

    Hoven, Andor F. van den; Braat, Manon N.G.J.A.; Prince, Jip F.; Doormaal, Pieter J. van; Leeuwen, Maarten S. van; Lam, Marnix G.E.H.; Bosch, Maurice A.A.J. van den [University Medical Center Utrecht, Department of Radiology and Nuclear Medicine, Utrecht (Netherlands)

    2017-01-15

    To compare right gastric (RGA) and segment 4 artery (A4) origin detection rates during radioembolisation workup between early and late arterial phase liver CT protocols. 100 consecutive patients who underwent liver CT between May 2012-January 2015 with early or late arterial phase protocol (n = 50 each, 10- vs. 20-s post-threshold delay) were included. RGA/A4 origin detection rates, assessed by two raters, and contrast-to-noise ratio (CNR) of the hepatic artery relative to the portal vein were compared between the protocols. The first-second rater scored the RGA origin as visible in 58-65 % (specific proportion of agreement 82 %, κ = 0.62); A4 origin in 96-89 % (94 %, κ = 0.54). Thirty-six percent of RGA origins not detectable by DSA were identified on CT. Origin detection rates were not significantly different for early/late arterial phases. Mean CNR was higher in the early arterial phase protocol (1.7 vs. 1.2, p < 0.001). A 10-s delay arterial phase CT protocol does not significantly improve detection of small intra- and extrahepatic branches. RGA origin detection requires further optimization, whereas A4/MHA origin detection is adequate, with good inter-rater reproducibility. CT remains important for preprocedural planning, because it may reveal arterial anatomy not discernible on DSA. (orig.)

  18. Propranolol modulates the collateral vascular responsiveness to vasopressin via a G(α)-mediated pathway in portal hypertensive rats.

    Science.gov (United States)

    Lee, Jing-Yi; Huo, Teh-Ia; Huang, Hui-Chun; Lee, Fa-Yauh; Lin, Han-Chieh; Chuang, Chiao-Lin; Chang, Ching-Chih; Wang, Sun-Sang; Lee, Shou-Dong

    2011-12-01

    Gastro-oesophageal variceal haemorrhage is one of the most dreadful complications of portal hypertension and can be controlled with vasoconstrictors. Nevertheless, sympathetic tone abnormality and vascular hyporesponsiveness in portal hypertension may impede the haemostatic effects of vasoconstrictors. Propranolol, a β-blocker binding the G-protein-coupled adrenoceptor, is a portal hypotensive agent. However, whether propranolol influences the collateral vasoresponse is unknown. Portal hypertension was induced by PVL (portal vein ligation) in Sprague-Dawley rats. In an acute study with an in situ perfusion model, the collateral responsiveness to AVP (arginine vasopressin) was evaluated with vehicle, propranolol (10 μmol/l), propranolol plus suramin (100 μmol/l, a G(α) inhibitor) or suramin pre-incubation. G(α) mRNA expression in the splenorenal shunt, the most prominent intra-abdominal collateral vessel, was measured. In the chronic study, rats received DW (distilled water) or propranolol (10 mg x kg(-1) of body weight x day(-1)) for 9 days. Then the concentration-response relationship of AVP and G(α) mRNA expression were assessed. Propranolol pre-incubation elevated the perfusion pressure changes of collaterals in response to AVP, which was inhibited by suramin. The splenorenal shunt G(αq) and G(α11) mRNA expression were enhanced by propranolol. The group treated with propranolol plus suramin had a down-regulation of G(α11) as compared with the propranolol group. Chronic propranolol treatment reduced mean arterial pressure, PP (portal pressure) and the perfusion pressure changes of collaterals to AVP. G(αs) expression was up-regulated. In conclusion, propranolol pre-incubation enhanced the portal-systemic collateral AVP responsiveness in portal hypertensive rats, which was related to G(αq) and G(α11) up-regulation. In contrast, the attenuated AVP responsiveness by chronic propranolol treatment was related to G(αs) up-regulation. The G(α) signalling

  19. Right ventricular pressure response to exercise in adults with isolated ventricular septal defect closed in early childhood.

    Science.gov (United States)

    Moller, Thomas; Lindberg, Harald; Lund, May Brit; Holmstrom, Henrik; Dohlen, Gaute; Thaulow, Erik

    2018-06-01

    We previously demonstrated an abnormally high right ventricular systolic pressure response to exercise in 50% of adolescents operated on for isolated ventricular septal defect. The present study investigated the prevalence of abnormal right ventricular systolic pressure response in 20 adult (age 30-45 years) patients who underwent surgery for early ventricular septal defect closure and its association with impaired ventricular function, pulmonary function, or exercise capacity. The patients underwent cardiopulmonary tests, including exercise stress echocardiography. Five of 19 patients (26%) presented an abnormal right ventricular systolic pressure response to exercise ⩾ 52 mmHg. Right ventricular systolic function was mixed, with normal tricuspid annular plane systolic excursion and fractional area change, but abnormal tricuspid annular systolic motion velocity (median 6.7 cm/second) and isovolumetric acceleration (median 0.8 m/second2). Left ventricular systolic and diastolic function was normal at rest as measured by the peak systolic velocity of the lateral wall and isovolumic acceleration, early diastolic velocity, and ratio of early diastolic flow to tissue velocity, except for ejection fraction (median 53%). The myocardial performance index was abnormal for both the left and right ventricle. Peak oxygen uptake was normal (mean z score -0.4, 95% CI -2.8-0.3). There was no association between an abnormal right ventricular systolic pressure response during exercise and right or left ventricular function, pulmonary function, or exercise capacity. Abnormal right ventricular pressure response is not more frequent in adult patients compared with adolescents. This does not support the theory of progressive pulmonary vascular disease following closure of left-to-right shunts.

  20. Extramural vascular invasion and response to neoadjuvant chemoradiotherapy in rectal cancer: Influence of the CpG island methylator phenotype.

    Science.gov (United States)

    Williamson, Jeremy Stuart; Jones, Huw Geraint; Williams, Namor; Griffiths, Anthony Paul; Jenkins, Gareth; Beynon, John; Harris, Dean Anthony

    2017-05-15

    To identify whether CpG island methylator phenotype (CIMP) is predictive of response to neoadjuvant chemoradiotherapy (NACRT) and outcomes in rectal cancer. Patients undergoing NACRT and surgical resection for rectal cancer in a tertiary referral centre between 2002-2011 were identified. Pre-treatment tumour biopsies were analysed for CIMP status (high, intermediate or low) using methylation specific PCR. KRAS and BRAF status were also determined using pyrosequencing analysis. Clinical information was extracted from case records and cancer services databases. Response to radiotherapy was measured by tumour regression scores determined upon histological examination of the resected specimen. The relationship between these molecular features, response to NACRT and oncological outcomes were analysed. There were 160 patients analysed with a median follow-up time of 46.4 mo. Twenty-one (13%) patients demonstrated high levels of CIMP methylation (CIMP-H) and this was significantly associated with increased risk of extramural vascular invasion (EMVI) compared with CIMP-L [8/21 (38%) vs 15/99 (15%), P = 0.028]. CIMP status was not related to tumour regression after radiotherapy or survival, however EMVI was significantly associated with adverse survival ( P CIMP status was significantly associated with KRAS mutation ( P = 0.01). There were 14 (9%) patients with a pathological complete response (pCR) compared to 116 (73%) patients having no or minimal regression after neoadjuvant chemoradiotherapy. Those patients with pCR had median survival of 106 mo compared to 65.8 mo with minimal regression, although this was not statistically significant ( P = 0.26). Binary logistic regression analysis of the relationship between EMVI and other prognostic features revealed, EMVI positivity was associated with poor overall survival, advanced "T" stage and CIMP-H but not nodal status, age, sex, KRAS mutation status and presence of local or systemic recurrence. We report a novel

  1. The survival condition and immunoregulatory function of adipose stromal vascular fraction (SVF in the early stage of nonvascularized adipose transplantation.

    Directory of Open Access Journals (Sweden)

    Ziqing Dong

    Full Text Available INTRODUCTION: Adipose tissue transplantation is one of the standard procedures for soft-tissue augmentation, reconstruction, and rejuvenation. However, it is unknown as to how the graft survives after transplantation. We thus seek out to investigate the roles of different cellular components in the survival of graft. MATERIALS & METHODS: The ratios of stromal vascular fraction (SVF cellular components from human adipose tissue were evaluated using flow cytometry. Human liposuction aspirates that were either mixed with marked SVF cells or PBS were transplanted into nude mice. The graft was harvested and stained on days 1,4,7 and 14. The inflammation level of both SVF group and Fat-only group were also evaluated. RESULTS: Flow cytometric analysis showed SVF cells mainly contained blood-derived cells, adipose-derived stromal cells (ASCs, and endothelial cells. Our study revealed that most cells are susceptible to death after transplantation, although CD34+ ASCs can remain viable for 14 days. Notably, we found that ASCs migrated to the peripheral edge of the graft. Moreover, the RT-PCR and the immuno-fluorescence examination revealed that although the SVF did not reduce the number of infiltrating immune cells (macrophages in the transplant, it does have an immunoregulatory function of up-regulating the expression of CD163 and CD206 and down-regulating that of IL-1β, IL-6. CONCLUSIONS: Our study suggests that the survival of adipose tissue after nonvascularized adipose transplantation may be due to the ASCs in SVF cells. Additionally, the immunoregulatory function of SVF cells may be indirectly contributing to the remolding of adipose transplant, which may lead to SVF-enriched adipose transplantation.

  2. EMMPRIN-Mediated Induction of Uterine and Vascular Matrix Metalloproteinases during Pregnancy and in Response to Estrogen and Progesterone

    OpenAIRE

    Dang, Yiping; Li, Wei; Tran, Victoria; Khalil, Raouf A.

    2013-01-01

    Pregnancy is associated with uteroplacental and vascular remodeling in order to adapt for the growing fetus and the hemodynamic changes in the maternal circulation. We have previously shown upregulation of uterine matrix metalloproteinases (MMPs) during pregnancy. Whether pregnancy-associated changes in MMPs are localized to the uterus or are generalized in feto-placental and maternal circulation is unclear. Also, the mechanisms causing the changes in uteroplacental and vascular MMPs during p...

  3. Culturally Responsive Literacy Practices in an Early Childhood Community

    Science.gov (United States)

    Bennett, Susan V.; Gunn, AnnMarie Alberton; Gayle-Evans, Guda; Barrera, Estanislado S.; Leung, Cynthia B.

    2018-01-01

    Early childhood educators continue to see an increase in their culturally diverse student population. As our country continues to grow as a multicultural nation, it is imperative that our early childhood classrooms embrace this rich diversity and provide experiences that affirm all students, families and communities. We (teacher educators)…

  4. Effects of nutritional plane and selenium supply during gestation on visceral organ mass and indices of intestinal growth and vascularity in primiparous ewes at parturition and during early lactation.

    Science.gov (United States)

    Objectives were to investigate effects of nutritional plane and Se supply during gestation on visceral organ mass and intestinal growth and vascularization in ewes at parturition and during early lactation. Primiparous Rambouillet ewes (n = 84) were allocated to 2 × 3 × 2 factorial arrangement of tr...

  5. Circulating serum interleukin-6, serum chitinase-3-like protein-1, and plasma vascular endothelial growth factor are not predictive for remission and radiographic progression in patients with early rheumatoid arthritis

    DEFF Research Database (Denmark)

    Brahe, C H; Dehlendorff, C; Østergaard, M

    2018-01-01

    OBJECTIVE: To investigate serum interleukin-6 (IL-6), serum chitinase-3-like protein-1 (YKL-40), and plasma vascular endothelial growth factor (VEGF) as measures of disease activity and predictors of clinical remission and radiographic progression in two early rheumatoid arthritis (RA) randomized...

  6. [Effects of low molecular weight heparin on the inflammatory response and vascular injury in rat after electric burn].

    Science.gov (United States)

    Jiang, Nanhong; Xie, Weiguo; Wang, Hui; Jin, Dongmei; Tan, Hong; Zhao, Chaoli

    2014-04-01

    To observe the effects of low molecular weight heparin (LMWH) on the inflammatory response and vascular injury in rat after electric burn. A homemade regulator and transformer apparatus was used to reproduce the model of electric burn (0.5 cm×0.5 cm in size) with depth from full-thickness to full-thickness skin plus muscle and bone on the middle of the inside of right hind limb in 60 Wistar rats. The open wounds were covered with 20 g/L sulfadiazine silver paste immediately after injury. The wound condition was observed every day. The injured rats were divided into group LMWH and control group (C) according to the random number table, with 30 rats in each group. Rats in group LMWH were given subcutaneous injection of LMWH (1 U/g) in abdominal wall, 2 times a day. No other treatment was given in rats in group C. On post burn day (PBD) 3, 5, and 10, 10 rats respectively of two groups were sacrificed. The damaged tissue of wound and that around the wound (1.0 cm×0.5 cm in size) were excised, and heart blood was obtained. The pathological changes and thrombosis in damaged tissue were observed with HE, Masson, and aldehyde fuchsin staining, and the thrombosis rate was calculated. Serum contents of TNF-α and endothelin-1 were determined with ELISA. The mRNA expression of TNF-α in damaged tissue was detected with RT-PCR. Data were processed with Levene homogeneity test, analysis of variance of factorial design, LSD- t test, SNK- q test, and Friedman M nonparametric test. (1) The injured limb of rats was obviously swollen after electric burn, which reached deeply to the muscle and bone. Compared with those of group C, the swelling of rats subsided slightly faster and the inflammatory response was lighter in group LMWH at each time point. (2) The necrosis of damaged tissue and profuse infiltration of inflammatory cells were observed. Dilatation of blood vessels, congestion and thrombosis, and swelling, necrosis, and desquamation of vascular endothelial cells were

  7. Calcium dynamics in vascular smooth muscle

    OpenAIRE

    Amberg, Gregory C.; Navedo, Manuel F.

    2013-01-01

    Smooth muscle cells are ultimately responsible for determining vascular luminal diameter and blood flow. Dynamic changes in intracellular calcium are a critical mechanism regulating vascular smooth muscle contractility. Processes influencing intracellular calcium are therefore important regulators of vascular function with physiological and pathophysiological consequences. In this review we discuss the major dynamic calcium signals identified and characterized in vascular smooth muscle cells....

  8. From genetics to response to injury: vascular smooth muscle cells in aneurysms and dissections of the ascending aorta.

    Science.gov (United States)

    Michel, Jean-Baptiste; Jondeau, Guillaume; Milewicz, Dianna M

    2018-03-15

    Vascular smooth muscle cells (vSMCs) play a crucial role in both the pathogenesis of Aneurysms and Dissections of the ascending thoracic aorta (TAAD) in humans and in the associated adaptive compensatory responses, since thrombosis and inflammatory processes are absent in the majority of cases. Aneurysms and dissections share numerous characteristics, including aetiologies and histopathological alterations: vSMC disappearance, medial areas of mucoid degeneration, and extracellular matrix (ECM) breakdown. Three aetiologies predominate in TAAD in humans: (i) genetic causes in heritable familial forms, (ii) an association with bicuspid aortic valves, and (iii) a sporadic degenerative form linked to the aortic aging process. Genetic forms include mutations in vSMC genes encoding for molecules of the ECM or the TGF-β pathways, or participating in vSMC tone. On the other hand, aneurysms and dissections, whatever their aetiologies, are characterized by an increase in wall permeability leading to transmural advection of plasma proteins which could interact with vSMCs and ECM components. In this context, blood-borne plasminogen appears to play an important role, because its outward convection through the wall is increased in TAAD, and it could be converted to active plasmin at the vSMC membrane. Active plasmin can induce vSMC disappearance, proteolysis of adhesive proteins, activation of MMPs and release of TGF-β from its ECM storage sites. Conversely, vSMCs could respond to aneurysmal biomechanical and proteolytic injury by an epigenetic phenotypic switch, including constitutional overexpression and nuclear translocation of Smad2 and an increase in antiprotease and ECM protein synthesis. In contrast, such an epigenetic phenomenon is not observed in dissections. In this context, dysfunction of proteins involved in vSMC tone are interesting to study, particularly in interaction with plasma protein transport through the wall and TGF-β activation, to establish the

  9. Soluble vascular endothelial growth factor (VEGF) receptor-1 inhibits migration of human monocytic THP-1 cells in response to VEGF.

    Science.gov (United States)

    Zhu, Cansheng; Xiong, Zhaojun; Chen, Xiaohong; Lu, Zhengqi; Zhou, Guoyu; Wang, Dunjing; Bao, Jian; Hu, Xueqiang

    2011-08-01

    We aimed to investigate the regulation and contribution of vascular endothelial growth factor (VEGF) and sFlt-1(1-3) to human monocytic THP-1 migration. Ad-sFlt-1/FLAG, a recombinant adenovirus carrying the human sFlt-1(1-3) (the first three extracellular domains of FLT-1, the hVEGF receptor-1) gene, was constructed. L929 cells were infected with Ad-sFlt-1/FLAG and the expression of sFlt-1 was detected by immunofluorescent assay and ELISA. Corning(®) Transwell(®) Filter Inserts containing polyethylene terephthalate (PET) membranes with pore sizes of 3 μm were used as an experimental model to simulate THP-1 migration. Five VEGF concentrations (0, 0.1, 1, 10 and 100 ng/ml), four concentrations of sFlt-1(1-3)/FLAG expression supernatants (0.1, 1, 10 and 100 ng/ml), and monocyte chemoattractant protein-1 (MCP-1, 10 ng/ml) were used to test the ability of THP-1 cells to migrate through PET membranes. The sFlt-1(1-3) gene was successfully recombined into Ad-sFlt-1/FLAG. sFlt-1(1-3) was expressed in L929 cells transfected with Ad-sFlt-1/FLAG. THP-1 cell migration increased with increasing concentrations of VEGF, while cell migration decreased with increasing concentrations of sFlt1(1-3)/FLAG. sFlt1(1-3)/FLAG had no effect on MCP-1-induced cell migration. This study demonstrated that VEGF is able to elicit a migratory response in THP-1 cells, and that sFlt-1(1-3) is an effective inhibitor of THP-1 migration towards VEGF.

  10. Dual function of CD70 in viral infection: modulator of early cytokine responses and activator of adaptive responses1

    OpenAIRE

    Allam, Atef; Swiecki, Melissa; Vermi, William; Ashwell, Jonathan D.; Colonna, Marco

    2014-01-01

    The role of the tumor necrosis factor family member CD70 in adaptive T cell responses has been intensively studied but its function in innate responses is still under investigation. Here we show that CD70 inhibits the early innate response to murine cytomegalovirus (MCMV) but is essential for the optimal generation of virus-specific CD8 T cells. CD70-/- mice reacted to MCMV infection with a robust type I interferon and proinflammatory cytokine response. This response was sufficient for initia...

  11. Early quantification of the therapeutic efficacy of the vascular disrupting agent, CKD-516, using dynamic contrast-enhanced ultrasonography in rabbit VX2 liver tumors

    Energy Technology Data Exchange (ETDEWEB)

    Joo, Ijin; Kim, Jung Hoon; Lee, Jeong Min; Choi, Jin Woo; Han, Joon Koo; Choi, Byung Ihn [Dept. of Radiology, Seoul National University Hospital, Seoul (Korea, Republic of)

    2014-03-15

    To evaluate the usefulness of dynamic contrast-enhanced ultrasonography (DCE-US) in the early quantification of hemodynamic change following administration of the vascular disrupting agent (VDA) CKD-516 using a rabbit VX2 liver tumor model. This study was approved by our institutional animal care and use committee. Eight VX2 liver-tumor-bearing rabbits were treated with intravenous CKD-516, and all underwent DCE-US using SonoVue before and again 2, 4, 6, and 24 hours following their treatment. The tumor perfusion parameters were obtained from the time-intensity curve of the DCE-US data. Repeated measures analysis of variance was performed to assess any significant change in tumor perfusion over time. Relative changes in the DCE-US parameters between the baseline and follow-up assessments were correlated with the relative changes in tumor size over the course of seven days using Pearson correlation. CKD-516 treatment resulted in significant changes in the DCE-US parameters, including the peak intensity, total area under the time-intensity curve (AUCtotal), and AUC during wash-out (AUCout) over time (P<0.05). Pairwise comparison tests revealed that the AUCtotal and AUC during wash-in (AUCin) seen on the two-hour follow-up were significantly lower than the baseline values (P<0.05). However, none of early changes in the DCE-US parameters until 24-hour follow-up showed a significant correlation with the relative changes in tumor size during seven days after CKD-516 treatment. Our results suggest that a novel VDA (CKD-516) can cause disruption of tumor perfusion as early as two hours after treatment and that the therapeutic effect of CKD-516 treatment can be effectively quantified using DCE-US.

  12. The influence of nifedipine and pertussis toxin (PTX) on vascular responsiveness to alpha1- and alpha2-adrenergic stimulation of isolated femoral arteries

    Czech Academy of Sciences Publication Activity Database

    Líšková, Silvia; Kuneš, Jaroslav; Paulis, Ĺudovít; Zicha, Josef

    2006-01-01

    Roč. 48, č. 4 (2006), s. 769-769 ISSN 0194-911X. [Annual Meeting of the European Council for Cardiovascular Research (ECCR) /11./. 29.09.2006-01.10.2006, La Colle sur Loup] R&D Projects: GA MZd NR7786 Institutional research plan: CEZ:AV0Z50110509 Keywords : nifedipine * pertussis toxin * vascular responsiveness * alpha1- and alpha2-adrenergic stimulation * femorel arteria Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

  13. Improvement of insulin sensitivity in response to exercise training in type 2 diabetes mellitus is associated with vascular endothelial growth factor A expression.

    Science.gov (United States)

    Wagner, Henrik; Fischer, Helene; Degerblad, Marie; Alvarsson, Michael; Gustafsson, Thomas

    2016-09-01

    Insulin sensitivity changes in response to exercise training demonstrate a large variation. Vascular endothelial growth factor A could promote increased insulin sensitivity through angiogenesis. We investigated associations between changes in expression of key genes and insulin sensitivity, aerobic capacity and glycaemic control following exercise training in diabetes mellitus type 2. Subjects with diabetes mellitus type 2 underwent 12 weeks of structured exercise. Euglycaemic clamp, exercise test and HbA1c were performed. Muscle biopsies were obtained for mRNA expression. A total of 16 subjects completed the study. Change in vascular endothelial growth factor A expression was positively associated with an increase in insulin sensitivity (p = 0.004) and with a decrease in HbA1c (p = 0.034). Vascular endothelial growth factor A receptor-1 expression showed similar associations. The variation in physical adaptation to exercise training in diabetes mellitus type 2 was associated with changes in expression of vascular endothelial growth factor A in muscle. This difference in induced gene expression could contribute to the variation in exercise training effects on insulin sensitivity. Measures of capillary blood flow need to be assessed in future studies. © The Author(s) 2016.

  14. Responsive feeding: establishing healthy eating behaviour early on ...

    African Journals Online (AJOL)

    2013-04-12

    Apr 12, 2013 ... facilitation of self-regulation skills early in life may predict future food intake ... eating behaviour through communicating their attitudes and beliefs about ..... as well as disturbances in self-esteem, body image and socialisation ...

  15. Vascular endothelium receptors and transduction mechanisms

    CERN Document Server

    Gillis, C; Ryan, Una; Proceedings of the Advanced Studies Institute on "Vascular Endothelium: Receptors and Transduction Mechanisms"

    1989-01-01

    Beyond their obvious role of a barrier between blood and tissue, vascular endothelial cells are now firmly established as active and essential participants in a host of crucial physiological and pathophysiological functions. Probably the two most important factors responsible for promoting the current knowledge of endothelial functions are 1) observations in the late sixties-early seventies that many non-ventilatory properties of the lung could be attributed to the pulmonary endothelium and 2) the establishment, in the early and mid-seventies of procedures for routine culture of vascular endothelial cells. Many of these endothelial functions require the presence of receptors on the surface of the plasma membrane. There is now evidence for the existence among others of muscarinic, a-and /3-adrenergic, purine, insulin, histamine, bradykinin, lipoprotein, thrombin, paf, fibronectin, vitronectin, interleukin and albumin receptors. For some of these ligands, there is evidence only for the existence of endothelial ...

  16. Altered Evoked Gamma-Band Responses Reveal Impaired Early Visual Processing in ADHD Children

    Science.gov (United States)

    Lenz, Daniel; Krauel, Kerstin; Flechtner, Hans-Henning; Schadow, Jeanette; Hinrichs, Hermann; Herrmann, Christoph S.

    2010-01-01

    Neurophysiological studies yield contrary results whether attentional problems of patients with attention-deficit/hyperactivity disorder (ADHD) are related to early visual processing deficits or not. Evoked gamma-band responses (GBRs), being among the first cortical responses occurring as early as 90 ms after visual stimulation in human EEG, have…

  17. Interleukin-6, vascular endothelial growth factor and transforming growth factor beta 1 in canine steroid responsive meningitis-arteritis

    Directory of Open Access Journals (Sweden)

    Maiolini Arianna

    2013-02-01

    Full Text Available Abstract Background Steroid Responsive Meningitis-Arteritis (SRMA is a common cause of inflammation of the canine central nervous system (CNS. To investigate if transforming growth factor beta 1 (TGF-β1, interleukin-6 (IL-6 and vascular endothelial growth factor (VEGF are involved in the production of excessive immunoglobulin A (IgA, the induction of acute phase proteins and in the development of a systemic necrotizing vasculitis, characteristic of SRMA, these three signalling proteins were evaluated. Results Cerebrospinal fluid (CSF and serum samples of dogs during the acute phase of SRMA (SRMA were tested for IL-6, VEGF and TGF- β1. Results were compared to those of dogs affected with SRMA during treatment (SRMA Th and during relapse (SRMA R, to dogs with other meningoencephalomyelitides (ME, with miscellaneous non-inflammatory diseases of the CNS (CNS-Mix, with idiopathic epilepsy (IE, with systemic inflammatory diseases (Syst. Infl. and with healthy dogs (Healthy. Concentrations of IL-6 and VEGF in CSF were significantly elevated in the SRMA group compared to the other disease categories (p 1 were increased in SRMA group, but statistically significant differences were found only in comparison with Healthy and CNS-Mix groups. No differences were detected in the serum concentrations of TGF-β1 between the different groups. In untreated SRMA patients, a positive correlation (rSpear = 0.3549; P = 0.0337 between concentrations of TGF-β1 and IgA concentration was found in CSF, while concentrations of IL-6 and VEGF in CSF positively correlated with the degree of pleocytosis (rSpear = 0.8323; P Spear = 0.5711; P = 0.0166, respectively. Conclusions Our results suggest that these three signalling proteins are biomarkers of disease activity in SRMA. VEGF might play an important role in the development of a systemic arteritis. TGF-β1 is considered to be involved in the excessive IgA production, while IL-6 in the pleocytosis

  18. RESPUESTAS CARDIOVASCULARES AL ENTRENAMIENTO DE FUERZA BAJO OCLUSIÓN VASCULAR [Cardiovascular responses to strength training under occlusive training

    Directory of Open Access Journals (Sweden)

    Sergio Benito Hernández

    2013-11-01

    Full Text Available El entrenamiento de la fuerza bajo oclusión vascular se muestra como una alternativa al entrenamiento de alta intensidad. El presente estudio muestra las respuestas cardiovasculares a este tipo de entrenamiento. 10 sujetos fueron sometidos a dos protocolos de entrenamiento oclusivo diferenciados por el peso levantado, (30% del peso máximo, post30, y 70% del peso máximo, post70. Se registraron los valores de tensión arterial sistólica (TAS, diastólica (TAD y frecuencia cardiaca (FC. Los resultados evidencian disminución significativa en TAS y TAD en el grupo post30 en 7 y 13 mm Hg respectivamente en referencia a los valores basales (p<0.05, resultando un descenso muy significativo en el grupo post70, 14 y 20 mm Hg respectivamente (p<0.005. Los valores de la FC no se vieron alterados por ninguno de los protocolos experimentales (p>0.05. Los efectos de tamaño para todos los grupos resultaron triviales (d<0.25. En conclusión los resultados del presente estudios presentan una tendencia a la reducción de la tensión arterial significativa en TAS y TAD en los protocolos de entrenamiento oclusivo, resultando más notable cuando se aplica la mayor intensidad de entrenamiento. Resultan necesarios más estudios que examinen el comportamiento de los parámetros cardiovasculares tras el entrenamiento de fuerza bajo oclusión vascular.AbstractOcclusive strength training is shown like an alternative to intensive training. Present study shown cardiovascular responses to this training. 10 subjects were subjected to two occlusion training protocols, differentiated by the weight lifted (30 % of maximum weight lifted, post30, and 70 % of maximum weight lifted, post70. The values of arterial systolic tension (TAS, diastolic (TAD and heart rate (FC were recorded. The results showing a significant decline in TAS and TAD after post30 of 7 and 13 mm Hg respectively from basis values (p<0.05, resulting a very significant decline in post70 group, 14 and 20 mm Hg

  19. Three-dimensional power Doppler ultrasound in the early assessment of response to concurrent chemo-radiotherapy for advanced cervical cancer.

    Science.gov (United States)

    Xu, Yan; Zhu, Lijing; Ru, Tong; Wang, Huanhuan; He, Jian; Zhou, Zhengyang; Yang, Xiaofeng

    2017-09-01

    Background Three-dimensional power Doppler ultrasound (3D-PDU) imaging has been widely applied to the differentiation of benign and malignant cervical lesions; however, its potential value for predicting response to chemo-radiotherapy has not been fully explored. Purpose To investigate the feasibility of 3D-PDU imaging in predicting treatment response in patients receiving concurrent chemo-radiotherapy (CCRT) for advanced cervical cancer. Material and Methods Fifty-two patients with advanced cervical cancer who received CCRT underwent 3D-PDU examinations at four timepoints: pre-therapy (baseline), 1 week and 2 weeks during, as well as immediately post CCRT. Final tumor response was determined by change in tumor size using magnetic resonance imaging (MRI). Cervical tumor volumes and vascular indices were calculated and compared with the clinical outcome. Results Of the 52 patients, 32 patients who completed all four examinations were included in the analyses: 21 were classified as complete response (CR) and 11 as partial response (PR). During the treatment, the CR group showed that 3D vascular indices (VI and VFI) significantly increased at 1 week ( P = 0.028, P = 0.017, respectively) then decreased at 2 weeks and obviously decreased at therapy completion (both P  0.05). Conclusion Prospective longitudinal 3D-PDU imaging may have potentials in monitoring early therapeutic response to CCRT in patients with cervical cancer.

  20. Transformation by Oncogenic Ras Expands the Early Genomic Response to Transforming Growth Factor β in Intestinal Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Carl E. Allen

    2008-10-01

    Full Text Available A substantial body of evidence implicates TGFβ as a tumor promoter in epithelial cells that have become resistant to its tumor suppressor activity. To better understand early, genome-wide TGFβ responses in cells resistant to growth inhibition by TGFβ, we used microarray analysis in a well-defined cell culture system of sensitive and resistant intestinal epithelial cells. TGFβ-regulated gene expression in TGFβ-growth-sensitive, nontransformed rat intestinal epithelial cells (RIE-1 was compared to expression in TGFβ-growth-resistant RIE cells stably transformed by oncogenic Ras(12V. Treatment of RIE-1 cells with 2 ng/ml TGFβ1 for 1 hour increased the expression of eight gene sequences by 2.6-fold or more, whereas eight were down regulated 2.6-fold. In RIE-Ras(12V cells, 42 gene sequences were upregulated and only 3 were down-regulated. Comparison of RIE and RIE-Ras(12V identified 37 gene sequences as unique, Ras-dependent genomic targets of TGFβ1. TGFβ-regulation of connective tissue growth factor and vascular endothelial growth factor, two genes up-regulated in RIE-Ras cells and previously implicated in tumor promotion, was independently confirmed and further characterized by Northern analysis. Our data indicate that overexpression of oncogenic Ras in intestinal epithelial cells confers a significantly expanded repertoire of robust, early transcriptional responses to TGFβ via signaling pathways yet to be fully elucidated but including the canonical Raf-1/MAPK/Erk pathway. Loss of sensitivity to growth inhibition by TGFβ does not abrogate TGFβ signaling and actually expands the early transcriptional response to TGFβ1. Expression of some of these genes may confer to Ras-transformed cells characteristics favorable for tumor promotion.

  1. Estrogen, vascular estrogen receptor and hormone therapy in postmenopausal vascular disease.

    Science.gov (United States)

    Khalil, Raouf A

    2013-12-15

    Cardiovascular disease (CVD) is less common in premenopausal women than men of the same age or postmenopausal women, suggesting vascular benefits of estrogen. Estrogen activates estrogen receptors ERα, ERβ and GPR30 in endothelium and vascular smooth muscle (VSM), which trigger downstream signaling pathways and lead to genomic and non-genomic vascular effects such as vasodilation, decreased VSM contraction and growth and reduced vascular remodeling. However, randomized clinical trials (RCTs), such as the Women's Health Initiative (WHI) and Heart and Estrogen/progestin Replacement Study (HERS), have shown little vascular benefits and even adverse events with menopausal hormone therapy (MHT), likely due to factors related to the MHT used, ER profile, and RCT design. Some MHT forms, dose, combinations or route of administration may have inadequate vascular effects. Age-related changes in ER amount, distribution, integrity and post-ER signaling could alter the vascular response to MHT. The subject's age, preexisting CVD, and hormone environment could also reduce the effects of MHT. Further evaluation of natural and synthetic estrogens, phytoestrogens, and selective estrogen-receptor modulators (SERMs), and the design of appropriate MHT combinations, dose, route and 'timing' could improve the effectiveness of conventional MHT and provide alternative therapies in the peri-menopausal period. Targeting ER using specific ER agonists, localized MHT delivery, and activation of specific post-ER signaling pathways could counter age-related changes in ER. Examination of the hormone environment and conditions associated with hormone imbalance such as polycystic ovary syndrome may reveal the causes of abnormal hormone-receptor interactions. Consideration of these factors in new RCTs such as the Kronos Early Estrogen Prevention Study (KEEPS) could enhance the vascular benefits of estrogen in postmenopausal CVD. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Early capillary flux homogenization in response to neural activation.

    Science.gov (United States)

    Lee, Jonghwan; Wu, Weicheng; Boas, David A

    2016-02-01

    This Brief Communication reports early homogenization of capillary network flow during somatosensory activation in the rat cerebral cortex. We used optical coherence tomography and statistical intensity variation analysis for tracing changes in the red blood cell flux over hundreds of capillaries nearly at the same time with 1-s resolution. We observed that while the mean capillary flux exhibited a typical increase during activation, the standard deviation of the capillary flux exhibited an early decrease that happened before the mean flux increase. This network-level data is consistent with the theoretical hypothesis that capillary flow homogenizes during activation to improve oxygen delivery. © The Author(s) 2015.

  3. Hemodialysis Decreases the Etiologically-Related Early Vascular Aging Observed in End-Stage Renal Disease: A 5-Year Follow-Up Study.

    Science.gov (United States)

    Bia, Daniel; Galli, Cintia; Zócalo, Yanina; Valtuille, Rodolfo; Wray, Sandra; Armentano, Ricardo; Cabrera-Fischer, Edmundo

    2017-01-01

    To analyze the early vascular aging (EVA) in end-stage renal disease (ESRD) patients, attempting to determine a potential association between EVA and the etiology of ESRD, and to investigate the association of hemodialysis and EVA in ESRD patients during a 5-year follow-up period. Carotid-femoral pulse wave velocity (cfPWV) was obtained in 151 chronically hemodialyzed patients (CHP) and 283 control subjects, and in 25 CHP, who were followed-up after a 5-year lapse. cfPWV increased in ESRD patients compared to control subjects. The cfPWV-age relationship was found to have a steeper increase in ESRD patients. The highest cfPWV and EVA values were observed in patients with diabetic nephropathy. Regression analysis demonstrated a significant reduction of the EVA in HD patients on a 5-year follow-up. Patients in ESRD showed higher levels of EVA. cfPWV and EVA differed in ESRD patients depending on their renal failure etiology. CHP showed an EVA reduction after a 5-year follow-up period. © 2016 S. Karger AG, Basel.

  4. Early diagnosis of congenital vascular malformation as a condition to rapid prevention of complications – case study

    Directory of Open Access Journals (Sweden)

    Dominika Jaguś

    2017-06-01

    Full Text Available Klippel–Trénaunay syndrome is a rare congenital condition characterised by a triad of symptoms: capillary-lymphatic-venous malformations, varicose veins and venous malformations as well as soft tissue and skeletal hypertrophy of the affected limb. In this article, we present a case of a 5-year-old boy with extensive vascular malformations of the lower limbs and the buttock region. In this case, manifestation of all three symptoms was gradual. At the age of 4 years, the patient was admitted to the Department of Imaging Diagnostics for further diagnosis, where the triad characteristic for Klippel–Trénaunay syndrome and popliteal vein agenesis were diagnosed. Currently, a multidisciplinary team takes care of the boy in the Children’s Memorial Health Institute. Early and accurate diagnosis allows for rapid prevention of complications associated with Klippel–Trénaunay syndrome and enables patient-tailored treatment.

  5. Elevated Amygdala Response to Faces following Early Deprivation

    Science.gov (United States)

    Tottenham, N.; Hare, T. A.; Millner, A.; Gilhooly, T.; Zevin, J. D.; Casey, B. J.

    2011-01-01

    A functional neuroimaging study examined the long-term neural correlates of early adverse rearing conditions in humans as they relate to socio-emotional development. Previously institutionalized (PI) children and a same-aged comparison group were scanned using functional magnetic resonance imaging (fMRI) while performing an Emotional Face Go/Nogo…

  6. Differences of Tc-99m HMPAO SPECT imaging in the early stage of subcortical vascular dementia compared with Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Park, Kyung Won; Kang, Do Young; Park, Min Jeong; Cheon, Sang Myung; Cha, Jae Kwan; Kim, Sang Ho; Kim, Jae Woo [College of Medicine, Dong-A University, Busan (Korea, Republic of)

    2007-12-15

    The aim of this study is to assess the specific patterns of regional cerebral blood flow (rCBF) in patients with the early stage of subcortical vascular dementia (SVaD) and Alzheimer's disease (AD) using Tc-99m HMPAO SPECT, and to compare the differences between the two conditions. Sixteen SVaD, 46 AD and 12 control subjects participated in this study. We included the patients with SVaD and AD according to NINCDS-ADRDA and NINDS-AIREN criteria. They were all matched for age, education and clinical dementia rating scores. Three groups were evaluated by Tc-99m HMPAO SPECT using statistical parametric mapping (SPM) for measuring rCBF. The SPECT data of patients with SVaD and AD were compared with those of normal control subjects and then compared with each other. SPM analysis of the SPECT image showed significant perfusion deficits on the right temporal region and thalamus, left insula and superior temporal gyrus, both cingulate gyri and frontal subgyri in patients with SVaD and on the left supramarginal gyrus, superior temporal gyrus, postcentral gyrus and inferior parietal lobule, right fugiform gyrus and both cingulate gyri in AD compared with control subjects (uncorrected {rho} < 0.01). SVaD patients revealed significant hypoperfusion in the right parahippocampal gyrus with cingulated gyrus, left insula and both frontal subgyral regions compared with AD (uncorrected {rho} < 0.01). Our study shows characteristic and different pattern of perfusion deficits in patients with SVaD and AD, and these results may be helpful to discriminate the two conditions in the early stage of illness.

  7. Early vascular aging in young and middle-aged ischemic stroke patients: the Norwegian Stroke in the Young Study.

    Directory of Open Access Journals (Sweden)

    Sahrai Saeed

    Full Text Available Ischemic stroke survivors have high risk of cardiovascular morbidity and mortality even at young age, suggesting that early arterial aging is common among such patients.We measured aortic stiffness by carotid-femoral pulse wave velocity (PWV in 205 patients (69% men aged 15-60 years with acute ischemic stroke in the prospective Norwegian Stroke in the Young Study. High for age carotid-femoral PWV was identified in the reference normogram.Patients were on average 49 ± 10 years old, 34% had a history of hypertension and 37% had metabolic syndrome (MetS. In the total study population, higher PWV was associated with history of hypertension (β = 0.18, higher age (β = 0.34, systolic blood pressure (BP (β = 0.28 and serum creatinine (β = 0.18 and lower high-density lipoprotein (HDL cholesterol (β = -0.10, all p < 0.01 in multivariate linear regression analysis (multiple R2 = 0.42, p < 0.001. High for age PWV was found in 18% of patients. In univariate analyses, known hypertension was associated with a 6-fold, MetS with a 4-fold and presence of carotid plaque with a 3.7-fold higher risk for high for age PWV (all p < 0.01. In multiple logistic regression analysis higher systolic BP (odds ratio [OR] 1.04; 95% confidence interval [CI] 1.02-1.06; p < 0.01, history of hypertension (OR 3.59; 95% CI 1.52-8.51; p < 0.01, low HDL cholesterol (OR 3.03; 95% CI 1.00-9.09; p = 0.05 and higher serum creatinine (OR 1.04; 95% CI 1.01-1.06; p < 0.01 were associated with high for age PWV.Higher PWV is common in younger and middle-aged ischemic stroke patients and associated with a clustering of classical cardiovascular risk factors. ClinicalTrials.gov NCT01597453.

  8. The genetic background affects the vascular response in T-type calcium channels 3.2 deficient mice

    DEFF Research Database (Denmark)

    Svenningsen, Per; Hansen, Pernille B L

    2016-01-01

    -type channels are the dominant Ca(2+) entry pathway in vascular smooth muscle cells, however, T-type calcium channels are also expressed in the cardiovascular system where they play a functional role in the regulation of both contraction and vasodilation in (Chen et al. 2003; Hansen et al. 2001). This article...... is protected by copyright. All rights reserved....

  9. Response of Vascular Plant Communities to Harvest in Southern Appalachian Mixed-Oak Forests: Two-Year Results

    Science.gov (United States)

    Bryan W. Wender; Sharon M. Hood; David W. Smith; Shepard M. Zedaker; David L. Loftis

    1999-01-01

    A long-term study has been established to monitor the effects of seven silvicultural prescriptions on vascular flora community attributes. Treatments include a control, understory vegetation control, group selection, two levels of shelterwoods, leave-tree, and clearcut. Second growing season. post-treatment results are compared to pre-harvest values for residual~...

  10. No effect of melatonin to modify surgical-stress response after major vascular surgery: a randomised placebo-controlled trial

    DEFF Research Database (Denmark)

    Kücükakin, B; Wilhelmsen, M; Lykkesfeldt, Jens

    2010-01-01

    A possible mechanism underlying cardiovascular morbidity after major vascular surgery may be the perioperative ischaemia-reperfusion with excessive oxygen-derived free-radical production and increased levels of circulating inflammatory mediators. We examined the effect of melatonin infusion during...... surgery and oral melatonin treatment for 3 days after surgery on biochemical markers of oxidative and inflammatory stress....

  11. Early feeding and early life housing conditions influence the response towards a noninfectious lung challenge in broilers.

    Science.gov (United States)

    Simon, K; de Vries Reilingh, G; Bolhuis, J E; Kemp, B; Lammers, A

    2015-09-01

    Early life conditions such as feed and water availability immediately post hatch (PH) and housing conditions may influence immune development and therefore immune reactivity later in life. The current study addressed the consequences of a combination of these 2 early life conditions for immune reactivity, i.e., the specific antibody response towards a non-infectious lung challenge. Broiler chicks received feed and water either immediately p.h. or with a 72 h delay and were either reared in a floor or a cage system. At 4 weeks of age, chicks received either an intra-tracheally administered Escherichia coli lipopolysaccharide (LPS)/Human Serum Albumin (HUSA) challenge or a placebo, and antibody titers were measured up to day 14 after administration of the challenge. Chicks housed on the floor and which had a delayed access to feed p.h. showed the highest antibody titers against HuSA. These chicks also showed the strongest sickness response and poorest performance in response to the challenge, indicating that chicks with delayed access to feed might be more sensitive to an environment with higher antigenic pressure. In conclusion, results from the present study show that early life feeding strategy and housing conditions influence a chick's response to an immune challenge later in life. These 2 early life factors should therefore be taken into account when striving for a balance between disease resistance and performance in poultry. © 2015 Poultry Science Association Inc.

  12. Outcome of poor response Paediatric AML using early SCT

    DEFF Research Database (Denmark)

    Wareham, Neval E; Heilmann, Carsten; Abrahamsson, Jonas

    2013-01-01

    ) or > 5% blasts after AM (n = 14, refractory disease). Poor response patients received intensively timed induction and proceeded to SCT when a donor was available. RESULTS: Thirty-one of 267 evaluable patients (12%) had a poor response. SCT was performed in 25; using matched unrelated donors in 13......BACKGROUND: Children with poor response acute myeloid leukaemia (AML) generally have a very poor outcome. Allogeneic stem cell transplantation (SCT) is often recommended for these children but the benefit is unclear. The aim of this study was to investigate survival for poor response AML patients...... treated with SCT. MATERIAL AND METHODS: Treatment was given according to the NOPHO-AML 2004 protocol. All patients received AIET (Cytarabine, Idarubicin, Etoposide, Thioguanine) and AM (Cytarabine, Mitoxantrone) as induction. We included poor response defined as > 15% blasts on day 15 after AIET (n = 17...

  13. Sensing of Vascular Permeability in Inflamed Vessel of Live Animal

    Directory of Open Access Journals (Sweden)

    Sang A Park

    2018-01-01

    Full Text Available Increase in vascular permeability is a conclusive response in the progress of inflammation. Under controlled conditions, leukocytes are known to migrate across the vascular barriers to the sites of inflammation without severe vascular rupture. However, when inflammatory state becomes excessive, the leakage of blood components may occur and can be lethal. Basically, vascular permeability can be analyzed based on the intensity of blood outflow. To evaluate the amount and rate of leakage in live mice, we performed cremaster muscle exteriorization to visualize blood flow and neutrophil migration. Using two-photon intravital microscopy of the exteriorized cremaster muscle venules, we found that vascular barrier function is transiently and locally disrupted in the early stage of inflammatory condition induced by N-formylmethionyl-leucyl-phenylalanine (fMLP. Measurement of the concentration of intravenously (i.v. injected Texas Red dextran inside and outside the vessels resulted in clear visualization of real-time increases in transient and local vascular permeability increase in real-time manner. We successfully demonstrated repeated leakage from a target site on a blood vessel in association with increasing severity of inflammation. Therefore, compared to other methods, two-photon intravital microscopy more accurately visualizes and quantifies vascular permeability even in a small part of blood vessels in live animals in real time.

  14. Histology atlas of the developing mouse hepatobiliary hemolymphatic vascular system with emphasis on embryonic days 11.5-18.5 and early postnatal development

    Science.gov (United States)

    A critical event in fetal development is the proper formation of the vascular system, of which the hepatobiliary system plays a pivotal role. This has lead pathologists and scientists to utilize transgenic mice to identify developmental disorders associated with the hepatobiliary vascular system. Va...

  15. Antibody response to pneumococcal vaccine in patients with early stage Hodgkin's disease

    DEFF Research Database (Denmark)

    Frederiksen, B; Specht, L; Henrichsen, J

    1989-01-01

    response to pneumococcal type antigens was similar in healthy adults and in patients with early stage HD before therapy. After treatment, postvaccination antibody response became negligible. Even up to 7 years after cessation of therapy patients were not able to raise a significant antibody response....

  16. Orthostatic function and the cardiovascular response to early mobilization after breast cancer surgery

    DEFF Research Database (Denmark)

    Gamborg Müller, Rasmus; Bundgaard-Nielsen, Morten; Kehlet, H

    2010-01-01

    procedures, because of an attenuated cardiovascular response, but the cardiovascular response and the incidence of orthostatic intolerance after minor procedures have not been clarified. We investigated the cardiovascular response and the incidence of orthostatic intolerance during early mobilization after...... breast cancer surgery....

  17. Capturing early signs of deterioration: the dutch-early-nurse-worry-indicator-score and its value in the Rapid Response System

    NARCIS (Netherlands)

    Douw, G.; Huisman-de Waal, G.J.; Zanten, A.R. van; Hoeven, J.G. van der; Schoonhoven, L.

    2017-01-01

    AIMS AND OBJECTIVES: To determine the predictive value of individual and combined dutch-early-nurse-worry-indicator-score indicators at various Early Warning Score levels, differentiating between Early Warning Scores reaching the trigger threshold to call a rapid response team and Early Warning

  18. Outcome of poor response paediatric AML using early SCT.

    Science.gov (United States)

    Wareham, Neval E; Heilmann, Carsten; Abrahamsson, Jonas; Forestier, Erik; Gustafsson, Britt; Ha, Shau-Yin; Heldrup, Jesper; Jahnukainen, Kirsi; Jónsson, Ólafur G; Lausen, Birgitte; Palle, Josefine; Zeller, Bernward; Hasle, Henrik

    2013-03-01

    Children with poor response acute myeloid leukaemia (AML) generally have a very poor outcome. Allogeneic stem cell transplantation (SCT) is often recommended for these children but the benefit is unclear. The aim of this study was to investigate survival for poor response AML patients treated with SCT. Treatment was given according to the NOPHO-AML 2004 protocol. All patients received AIET (Cytarabine, Idarubicin, Etoposide, Thioguanine) and AM (Cytarabine, Mitoxantrone) as induction. We included poor response defined as > 15% blasts on day 15 after AIET (n = 17) or > 5% blasts after AM (n = 14, refractory disease). Poor response patients received intensively timed induction and proceeded to SCT when a donor was available. Thirty-one of 267 evaluable patients (12%) had a poor response. SCT was performed in 25; using matched unrelated donors in 13, matched sibling donors in 6, cord blood donor in 4, and haploidentical donor in two. The median follow-up for the 31 poor responding patients was 2.6 years (range 0.4 - 8.1 years) and 3-year probability of survival 70% (95% CI 59-77%). The poor responders in the NOPHO-AML 2004 protocol had a favourable prognosis treated with time-intensive induction followed by SCT. © 2012 John Wiley & Sons A/S.

  19. EMMPRIN-mediated induction of uterine and vascular matrix metalloproteinases during pregnancy and in response to estrogen and progesterone.

    Science.gov (United States)

    Dang, Yiping; Li, Wei; Tran, Victoria; Khalil, Raouf A

    2013-09-15

    Pregnancy is associated with uteroplacental and vascular remodeling in order to adapt for the growing fetus and the hemodynamic changes in the maternal circulation. We have previously shown upregulation of uterine matrix metalloproteinases (MMPs) during pregnancy. Whether pregnancy-associated changes in MMPs are localized to the uterus or are generalized in feto-placental and maternal circulation is unclear. Also, the mechanisms causing the changes in uteroplacental and vascular MMPs during pregnancy are unclear. MMPs expression, activity and tissue distribution were measured in uterus, placenta and aorta of virgin, mid-pregnant (mid-Preg) and late pregnant (late-Preg) rats. Western blots and gelatin zymography revealed increases in MMP-2 and -9 in uterus and aorta of late-Preg compared with virgin and mid-Preg rats. In contrast, MMP-2 and -9 were decreased in placenta of late-Preg versus mid-Preg rats. Extracellular MMP inducer (EMMPRIN) was increased in uterus and aorta of pregnant rats, but was less in placenta of late-Preg than mid-Preg rats. Prolonged treatment of uterus or aorta of virgin rats with 17β-estradiol and progesterone increased the amount of EMMPRIN, MMP-2 and -9, and the sex hormone-induced increases in MMPs were prevented by EMMPRIN neutralizing antibody. Immunohistochemistry revealed that MMP-2 and -9 and EMMPRIN increased in uterus and aorta of pregnant rats, but decreased in placenta of late-Preg versus mid-Preg rats. Thus pregnancy-associated upregulation of uterine MMPs is paralleled by increased vascular MMPs, and both are mediated by EMMPRIN and induced by estrogen and progesterone, suggesting similar role of MMPs in uterine and vascular tissue remodeling and function during pregnancy. The decreased MMPs and EMMPRIN in placenta of late-Preg rats suggests reduced role of MMPs in feto-placental circulation during late pregnancy. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Fructose intake exacerbates the contractile response elicited by norepinephrine in mesenteric vascular bed of rats via increased endothelial prostanoids.

    Science.gov (United States)

    Sousa, Glauciene J; Oliveira, Phablo Wendell C; Nogueira, Breno V; Melo, Antônio F; Faria, Thaís de Oliveira; Meira, Eduardo Frizera; Mill, José G; Bissoli, Nazaré S; Baldo, Marcelo P

    2017-10-01

    Chronic fructose intake induces major cardiovascular and metabolic disturbances and is associated with the development of hypertension due to changes in vascular function. We hypothesized that high fructose intake for 6 weeks would cause metabolic syndrome and lead to initial vascular dysfunction. Male Wistar rats were assigned to receive fructose (FRU, 10%) or drinking water (CON) for 6 weeks. Systolic blood pressure was evaluated by tail plethysmography. Fasting glucose, insulin and glucose tolerance were measured at the end of the follow-up. Mesenteric vascular bed reactivity was tested before and after pharmacological blockade. Western blot analysis was performed for iNOS, eNOS, Nox2 and COX-2. DHE staining was used for vascular superoxide anion detection. Vessel structure was evaluated by optical and electronic microscopy. Fructose intake did not alter blood pressure, but did increase visceral fat deposition and fasting glucose as well as impair insulin and glucose tolerance. Fructose increased NE-induced vasoconstriction compared with CON, and this difference was abrogated by indomethacin perfusion as well as endothelium removal. ACh-induced relaxation was preserved, and the NO modulation tested after L-NAME perfusion was similar between groups. SNP-induced relaxation was not altered. Inducible NOS was increased; however, there were no changes in eNOS, Nox2 or COX-2 protein expression. Basal or stimulated superoxide anion production was not changed by fructose intake. In conclusion, high fructose intake increased NE-induced vasoconstriction through the endothelial prostanoids even in the presence of a preserved endothelium-mediated relaxation. No major changes in vessel structure were detected. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Early Alzheimer's and Parkinson's disease pathology in urban children: Friend versus Foe responses--it is time to face the evidence.

    Science.gov (United States)

    Calderón-Garcidueñas, Lilian; Franco-Lira, Maricela; Mora-Tiscareño, Antonieta; Medina-Cortina, Humberto; Torres-Jardón, Ricardo; Kavanaugh, Michael

    2013-01-01

    Chronic exposure to particulate matter air pollution is known to cause inflammation leading to respiratory- and cardiovascular-related sickness and death. Mexico City Metropolitan Area children exhibit an early brain imbalance in genes involved in oxidative stress, inflammation, and innate and adaptive immune responses. Early dysregulated neuroinflammation, brain microvascular damage, production of potent vasoconstrictors, and perturbations in the integrity of the neurovascular unit likely contribute to progressive neurodegenerative processes. The accumulation of misfolded proteins coincides with the anatomical distribution observed in the early stages of both Alzheimer's and Parkinson's diseases. We contend misfolding of hyperphosphorylated tau (HPπ), alpha-synuclein, and beta-amyloid could represent a compensatory early protective response to the sustained systemic and brain inflammation. However, we favor the view that the chronic systemic and brain dysregulated inflammation and the diffuse vascular damage contribute to the establishment of neurodegenerative processes with childhood clinical manifestations. Friend turns Foe early; therefore, implementation of neuroprotective measures to ameliorate or stop the inflammatory and neurodegenerative processes is warranted in exposed children. Epidemiological, cognitive, structural, and functional neuroimaging and mechanistic studies into the association between air pollution exposures and the development of neuroinflammation and neurodegeneration in children are of pressing importance for public health.

  2. Spectral imaging based in vivo model system for characterization of tumor microvessel response to vascular targeting agents

    Science.gov (United States)

    Wankhede, Mamta

    Functional vasculature is vital for tumor growth, proliferation, and metastasis. Many tumor-specific vascular targeting agents (VTAs) aim to destroy this essential tumor vasculature to induce indirect tumor cell death via oxygen and nutrition deprivation. The tumor angiogenesis-inhibiting anti-angiogenics (AIs) and the established tumor vessel targeting vascular disrupting agents (VDAs) are the two major players in the vascular targeting field. Combination of VTAs with conventional therapies or with each other, have been shown to have additive or supra-additive effects on tumor control and treatment. Pathophysiological changes post-VTA treatment in terms of structural and vessel function changes are important parameters to characterize the treatment efficacy. Despite the abundance of information regarding these parameters acquired using various techniques, there remains a need for a quantitative, real-time, and direct observation of these phenomenon in live animals. Through this research we aspired to develop a spectral imaging based mouse tumor system for real-time in vivo microvessel structure and functional measurements for VTA characterization. A model tumor system for window chamber studies was identified, and then combinatorial effects of VDA and AI were characterized in model tumor system. (Full text of this dissertation may be available via the University of Florida Libraries web site. Please check http://www.uflib.ufl.edu/etd.html)

  3. Acute ingestion of a novel whey-derived peptide improves vascular endothelial responses in healthy individuals: a randomized, placebo controlled trial

    Directory of Open Access Journals (Sweden)

    Kupchak Brian R

    2009-07-01

    Full Text Available Abstract Background Whey protein is a potential source of bioactive peptides. Based on findings from in vitro experiments indicating a novel whey derived peptide (NOP-47 increased endothelial nitric oxide synthesis, we tested its effects on vascular function in humans. Methods A randomized, placebo-controlled, crossover study design was used. Healthy men (n = 10 and women (n = 10 (25 ± 5 y, BMI = 24.3 ± 2.3 kg/m2 participated in two vascular testing days each preceded by 2 wk of supplementation with a single dose of 5 g/day of a novel whey-derived peptide (NOP-47 or placebo. There was a 2 wk washout period between trials. After 2 wk of supplementation, vascular function in the forearm and circulating oxidative stress and inflammatory related biomarkers were measured serially for 2 h after ingestion of 5 g of NOP-47 or placebo. Macrovascular and microvascular function were assessed using brachial artery flow mediated dilation (FMD and venous occlusion strain gauge plethysmography. Results Baseline peak FMD was not different for Placebo (7.7% and NOP-47 (7.8%. Placebo had no effect on FMD at 30, 60, and 90 min post-ingestion (7.5%, 7.2%, and 7.6%, respectively whereas NOP-47 significantly improved FMD responses at these respective postprandial time points compared to baseline (8.9%, 9.9%, and 9.0%; P P = 0.008 for time × trial interaction. Plasma myeloperoxidase was increased transiently by both NOP-47 and placebo, but there were no changes in markers inflammation. Plasma total nitrites/nitrates significantly decreased over the 2 hr post-ingestion period and were lower at 120 min after placebo (-25% compared to NOP-47 (-18%. Conclusion These findings indicate that supplementation with a novel whey-derived peptide in healthy individuals improves vascular function.

  4. Magnetic source localization of early visual mismatch response

    NARCIS (Netherlands)

    Susac, A.; Heslenfeld, D.J.; Huonker, R.; Supek, S.

    2014-01-01

    Previous studies have reported a visual analogue of the auditory mismatch negativity (MMN) response that is based on sensory memory. The neural generators and attention dependence of the visual MMN (vMMN) still remain unclear. We used magnetoencephalography (MEG) and spatio-temporal source

  5. Evaluation of Vascular Endothelial Growth Factor as a Prognostic Marker for Local Relapse in Early-Stage Breast Cancer Patients Treated With Breast-Conserving Therapy

    International Nuclear Information System (INIS)

    Moran, Meena S.; Yang Qifeng; Goyal, Sharad; Harris, Lyndsay; Chung, Gina; Haffty, Bruce G.

    2011-01-01

    Purpose: Vascular endothelial growth factor (VEGF) is an important protein involved in the process of angiogenesis that has been found to correlate with relapse-free and overall survival in breast cancer, predominantly in locally advanced and metastatic disease. A paucity of data is available on the prognostic implications of VEGF in early-stage breast cancer; specifically, its prognostic value for local relapse after breast-conserving therapy (BCT) is largely unknown. The purpose of our study was to assess VEGF expression in a cohort of early-stage breast cancer patients treated with BCT and to correlate the clinical and pathologic features and outcomes with overexpression of VEGF. Methods and Materials: After obtaining institutional review board approval, the paraffin specimens of 368 patients with early-stage breast cancer treated with BCT between 1975 and 2005 were constructed into tissue microarrays with twofold redundancy. The tissue microarrays were stained for VEGF and read by a trained pathologist, who was unaware of the clinical details, as positive or negative according the standard guidelines. The clinical and pathologic data, long-term outcomes, and results of VEGF staining were analyzed. Results: The median follow-up for the entire cohort was 6.5 years. VEGF expression was positive in 56 (15%) of the 368 patients. Although VEGF expression did not correlate with age at diagnosis, tumor size, nodal status, histologic type, family history, estrogen receptor/progesterone receptor status, or HER-2 status, a trend was seen toward increased VEGF expression in the black cohort (26% black vs. 13% white, p = .068). Within the margin-negative cohort, VEGF did not predict for local relapse-free survival (RFS) (96% vs. 95%), nodal RFS (100% vs. 100%), distant metastasis-free survival (91% vs. 92%), overall survival (92% vs. 97%), respectively (all p >.05). Subset analysis revealed that VEGF was highly predictive of local RFS in node-positive, margin

  6. Early results of experiments with responsive open learning environments

    OpenAIRE

    Friedrich, M.; Wolpers, M.; Shen, R.; Ullrich, C.; Klamma, R.; Renzel, D.; Richert, A.; Heiden, B. von der

    2011-01-01

    Responsive open learning environments (ROLEs) are the next generation of personal learning environments (PLEs). While PLEs rely on the simple aggregation of existing content and services mainly using Web 2.0 technologies, ROLEs are transforming lifelong learning by introducing a new infrastructure on a global scale while dealing with existing learning management systems, institutions, and technologies. The requirements engineering process in highly populated test-beds is as important as the t...

  7. Characteristic pattern of cerebral perfusion in patients with the early stage of subcortical vascular dementia compared with Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Young Jin; Kang, Do Young; Park, Kyung Won; Cheon, Sang Myung; Kim, Jong Kuk; Kim, Jae Woo [Dong-A University School of Medicine, Busan (Korea, Republic of)

    2004-07-01

    Brain perfusion SPECT has been commonly used to evaluate several different types of dementia. The aim of this study is to assess the specific patterns of regional cerebral blood flow (rCBF) in patients with the early stage of subcortical vascular dementia (SVD) and Alzheimer's disease (AD) using Tc-99m HMPAO SPECT, and to compare the differences between the two conditions. Sixteen SVD (mean age; 68.0{+-}7.0 years, educational period; 6.3{+-}5.6 years, CDR; 0.80{+-}0.26). 46 AD (mean age; 69.9{+-}7.4 years, educational period; 5.4{+-}4.7 years, CDR; 0.86{+-}0.23) and 12 normal control subjects (mean age; 67.1{+-}7.7 years, educational period; 6.2{+-}4.2 years) participated in this study. We included the patients with SVD and AD according to NINCDS-ADRDA criteria for probable AD and NINDS-AIREN criteria for probable or possible VD. They were all matched for age, education and clinical dementia scale scores. SPM analysis of the SPECT image showed significant perfusion deficits on the right temporal region and right thalamus, left insula and superior temporal gyrus, both cingulate gyri and frontal subgyral regions in patients with SVD and on the left supramarginal gyrus, superior temporal gyrus, postcentral gyrus and inferior parietal lobule, right fugiform gyrus and both cingulate gyri in patients with AD compared with control subjects (uncorrected p<0.01). SVD patients revealed significant hypoperfusion in the right parahippocampal gyrus, right cingulated gyrus, left insula, and both frontal subgyral regions compared with AD patients (uncorrected p<0.01). SVD patients revealed significant hyperperfusion in right superior frontal gyrus, left pre- and postcentral gyri, left paracentral lobule, left precuneus and both medial frontal gyri compared with AD patients (uncorrected p<0.01). Our study shows characteristic and different pattern of perfusion deficits in patients with SVD and AD, and these results may be helpful to discriminate the two conditions in the

  8. Dual function of CD70 in viral infection: modulator of early cytokine responses and activator of adaptive responses1

    Science.gov (United States)

    Allam, Atef; Swiecki, Melissa; Vermi, William; Ashwell, Jonathan D.; Colonna, Marco

    2014-01-01

    The role of the tumor necrosis factor family member CD70 in adaptive T cell responses has been intensively studied but its function in innate responses is still under investigation. Here we show that CD70 inhibits the early innate response to murine cytomegalovirus (MCMV) but is essential for the optimal generation of virus-specific CD8 T cells. CD70-/- mice reacted to MCMV infection with a robust type I interferon and proinflammatory cytokine response. This response was sufficient for initial control of MCMV, although at later time points, CD70-/- mice became more susceptible to MCMV infection. The heightened cytokine response during the early phase of MCMV infection in CD70-/- mice was paralleled by a reduction in regulatory T cells (Treg). Treg from naïve CD70-/- mice were not as efficient at suppressing T cell proliferation compared to Treg from naïve WT mice and depletion of Treg during MCMV infection in Foxp3-DTR mice or in WT mice recapitulated the phenotype observed in CD70-/- mice. Our study demonstrates that while CD70 is required for the activation of the antiviral adaptive response, it has a regulatory role in early cytokine responses to viruses such as MCMV, possibly through maintenance of Treg survival and function. PMID:24913981

  9. Dual effects of fructose on ChREBP and FoxO1/3α are responsible for AldoB up-regulation and vascular remodelling.

    Science.gov (United States)

    Cao, Wei; Chang, Tuanjie; Li, Xiao-Qiang; Wang, Rui; Wu, Lingyun

    2017-02-01

    Increased production of methylglyoxal (MG) in vascular tissues is one of the causative factors for vascular remodelling in different subtypes of metabolic syndrome, including hypertension and insulin resistance. Fructose-induced up-regulation of aldolase B (AldoB) contributes to increased vascular MG production but the underlying mechanisms are unclear. Serum levels of MG and fructose were determined in diabetic patients with hypertension. MG level had significant positive correlations with blood pressure and fructose level respectively. C57BL/6 mice were fed with control or fructose-enriched diet for 3 months and ultrasonographic and histologic analyses were performed to evaluate arterial structural changes. Fructose-fed mice exhibited hypertension and high levels of serum MG with normal glucose level. Fructose intake increased blood vessel wall thickness and vascular smooth muscle cell (VSMC) proliferation. Western blotting and real-time PCR analysis revealed that AldoB level was significantly increased in both the aorta of fructose-fed mice and the fructose-treated VSMCs, whereas aldolase A (AldoA) expression was not changed. The knockdown of AldoB expression prevented fructose-induced MG overproduction and VSMC proliferation. Moreover, fructose significantly increased carbohydrate-responsive element-binding protein (ChREBP), phosphorylated FoxO1/3α and Akt1 levels. Fructose induced translocation of ChREBP from the cytosol to nucleus and activated AldoB gene expression, which was inhibited by the knockdown of ChREBP. Meanwhile, fructose caused FoxO1/3α shuttling from the nucleus to cytosol and inhibited its binding to AldoB promoter region. Fructose-induced AldoB up-regulation was suppressed by Akt1 inhibitor but enhanced by FoxO1/3α siRNA. Collectively, fructose activates ChREBP and inactivates FoxO1/3α pathways to up-regulate AldoB expression and MG production, leading to vascular remodelling. © 2017 The Author(s). published by Portland Press Limited on

  10. VASCULAR SURGERY

    African Journals Online (AJOL)

    2016-06-02

    Jun 2, 2016 ... with the literature from South Africa over the last four decades, and reflects the high rate of interpersonal violence in the country.14,15 As expected, cervical ... via the intact circle of Willis in young patients is the most likely explanation for the lack of strokes. Five patients were referred to the Durban vascular ...

  11. Vascular Disorders

    Science.gov (United States)

    ... All Topics A-Z Videos Infographics Symptom Picker Anatomy Bones Joints Muscles Nerves Vessels Tendons About Hand Surgery What is a Hand Surgeon? What is a Hand Therapist? Media Find a Hand Surgeon Home Anatomy Vascular Disorders Email to a friend * required fields ...

  12. Separating neural and vascular effects of caffeine using simultaneous EEG–FMRI: Differential effects of caffeine on cognitive and sensorimotor brain responses

    Science.gov (United States)

    Diukova, Ana; Ware, Jennifer; Smith, Jessica E.; Evans, C. John; Murphy, Kevin; Rogers, Peter J.; Wise, Richard G.

    2012-01-01

    The effects of caffeine are mediated through its non-selective antagonistic effects on adenosine A1 and A2A adenosine receptors resulting in increased neuronal activity but also vasoconstriction in the brain. Caffeine, therefore, can modify BOLD FMRI signal responses through both its neural and its vascular effects depending on receptor distributions in different brain regions. In this study we aim to distinguish neural and vascular influences of a single dose of caffeine in measurements of task-related brain activity using simultaneous EEG–FMRI. We chose to compare low-level visual and motor (paced finger tapping) tasks with a cognitive (auditory oddball) task, with the expectation that caffeine would differentially affect brain responses in relation to these tasks. To avoid the influence of chronic caffeine intake, we examined the effect of 250 mg of oral caffeine on 14 non and infrequent caffeine consumers in a double-blind placebo-controlled cross-over study. Our results show that the task-related BOLD signal change in visual and primary motor cortex was significantly reduced by caffeine, while the amplitude and latency of visual evoked potentials over occipital cortex remained unaltered. However, during the auditory oddball task (target versus non-target stimuli) caffeine significantly increased the BOLD signal in frontal cortex. Correspondingly, there was also a significant effect of caffeine in reducing the target evoked response potential (P300) latency in the oddball task and this was associated with a positive potential over frontal cortex. Behavioural data showed that caffeine also improved performance in the oddball task with a significantly reduced number of missed responses. Our results are consistent with earlier studies demonstrating altered flow-metabolism coupling after caffeine administration in the context of our observation of a generalised caffeine-induced reduction in cerebral blood flow demonstrated by arterial spin labelling (19

  13. Kinetics of the early adaptive response and adaptation threshold dose

    International Nuclear Information System (INIS)

    Mendiola C, M.T.; Morales R, P.

    2003-01-01

    The expression kinetics of the adaptive response (RA) in mouse leukocytes in vivo and the minimum dose of gamma radiation that induces it was determined. The mice were exposed 0.005 or 0.02 Gy of 137 Cs like adaptation and 1h later to the challenge dose (1.0 Gy), another group was only exposed at 1.0 Gy and the damage is evaluated in the DNA with the rehearsal it makes. The treatment with 0. 005 Gy didn't induce RA and 0. 02 Gy causes a similar effect to the one obtained with 0.01 Gy. The RA was show from an interval of 0.5 h being obtained the maximum expression with 5.0 h. The threshold dose to induce the RA is 0.01 Gy and in 5.0 h the biggest quantity in molecules is presented presumably that are related with the protection of the DNA. (Author)

  14. Enhanced Recovery after Vascular Surgery

    Directory of Open Access Journals (Sweden)

    Milena D. Stojanovic

    2018-01-01

    Full Text Available The beginnings of the enhanced recovery after surgery (ERAS program were first developed for patients in colorectal surgery, and after it was established as the standard of care in this surgical field, it began to be applied in many others surgical areas. This is multimodal, evidence-based approach program and includes simultaneous optimization of preoperative status of patients, adequate selection of surgical procedure and postoperative management. The aim of this program is to reduce complications, the length of hospital stay and to improve the patients outcome. Over the past decades, special attention was directed to the postoperative management in vascular surgery, especially after major vascular surgery because of the great risk of multiorgan failure, such as: respiratory failure, myocardial infarction, hemodynamic instability, coagulopathy, renal failure, neurological disorders, and intra-abdominal complications. Although a lot of effort was put into it, there is no unique acceptable program for ERAS in this surgical field, and there is still a need to point out the factors responsible for postoperative outcomes of these patients. So far, it is known that special attention should be paid to already existing diseases, type and the duration of the surgical intervention, hemodynamic and fluid management, nutrition, pain management, and early mobilization of patients.

  15. Vascular emergencies in liver trauma

    Energy Technology Data Exchange (ETDEWEB)

    Taourel, P. [Centre Hospitalier Universitaire Lapeyronie, Montpellier (France)], E-mail: p-taourel@chu-montpellier.fr; Vernhet, H. [Centre Hospitalier Universitaire Arnaud de Villeneuve, Montpellier (France); Suau, A.; Granier, C. [Centre Hospitalier Universitaire Lapeyronie, Montpellier (France); Lopez, F.M. [Centre Hospitalier Universitaire, Nimes (France); Aufort, S. [Centre Hospitalier Universitaire Lapeyronie, Montpellier (France)

    2007-10-15

    The use of CT in the diagnosis and management of liver trauma is responsible for the shift from routine surgical versus non-surgical treatment in the management of traumatic liver injuries, even when they are of high grade. The main cause of compli cation and of death in liver trauma is related to vascular injury. The goal of this review focussed on the vascular complications of liver trauma is to describe the elementary lesions shown by CT in liver trauma including laceration, parenchymal hematoma and contusions, partial devascularisation, subcapsular hematomas, hemoperitoneum, active bleeding, pseudoaneurysm of the hepatic artery, bile leak, and periportal oedema, to illustrate the possible pitfalls in CT diagnosis of liver trauma and to underline the key-points which may absolutely be present in a CT report of liver trauma. Then we will remind the grading system based on the CT features and we will analyze the interest and limitations of such grading systems. Last we will discuss the diagnostic strategy at the early phase in patients with suspected liver trauma according to their clinical conditions and underline the conditions of arterial embolization, and then we will discuss the diagnosis strategy at the delayed phase according to the suspected complications.

  16. Vascular emergencies in liver trauma

    International Nuclear Information System (INIS)

    Taourel, P.; Vernhet, H.; Suau, A.; Granier, C.; Lopez, F.M.; Aufort, S.

    2007-01-01

    The use of CT in the diagnosis and management of liver trauma is responsible for the shift from routine surgical versus non-surgical treatment in the management of traumatic liver injuries, even when they are of high grade. The main cause of compli cation and of death in liver trauma is related to vascular injury. The goal of this review focussed on the vascular complications of liver trauma is to describe the elementary lesions shown by CT in liver trauma including laceration, parenchymal hematoma and contusions, partial devascularisation, subcapsular hematomas, hemoperitoneum, active bleeding, pseudoaneurysm of the hepatic artery, bile leak, and periportal oedema, to illustrate the possible pitfalls in CT diagnosis of liver trauma and to underline the key-points which may absolutely be present in a CT report of liver trauma. Then we will remind the grading system based on the CT features and we will analyze the interest and limitations of such grading systems. Last we will discuss the diagnostic strategy at the early phase in patients with suspected liver trauma according to their clinical conditions and underline the conditions of arterial embolization, and then we will discuss the diagnosis strategy at the delayed phase according to the suspected complications

  17. The Role Played by the Family in Shaping Early and Middle Adolescent Civic Responsibility

    Science.gov (United States)

    Lenzi, Michela; Vieno, Alessio; Santinello, Massimo; Nation, Maury; Voight, Adam

    2014-01-01

    Adopting a multi-informant methodology, the current study examines the relative influence of multiple parental characteristics (civic responsibility, encouragement of civic action, parent-youth closeness) on adolescents' civic responsibility (local and global). The participants were 384 early and middle adolescents (47.9% male), randomly selected…

  18. Proteomic identification of early salicylate- and flg22-responsive redox-sensitive proteins in Arabidopsis

    KAUST Repository

    Liu, Peng; Zhang, Huoming; Yu, Boying; Xiong, Liming; Xia, Yiji

    2015-01-01

    in Arabidopsis cells during the early response to salicylate or flg22, two defense pathway elicitors that are known to disturb cellular redox homeostasis. Among the salicylate- and/or flg22-responsive redox-sensitive proteins are those involved in transcriptional

  19. Selection of an early biomarker for vascular normalization using dynamic contrast-enhanced ultrasonography to predict outcomes of metastatic patients treated with bevacizumab.

    Science.gov (United States)

    Lassau, N; Coiffier, B; Kind, M; Vilgrain, V; Lacroix, J; Cuinet, M; Taieb, S; Aziza, R; Sarran, A; Labbe-Devilliers, C; Gallix, B; Lucidarme, O; Ptak, Y; Rocher, L; Caquot, L M; Chagnon, S; Marion, D; Luciani, A; Feutray, S; Uzan-Augui, J; Benatsou, B; Bonastre, J; Koscielny, S

    2016-10-01

    Dynamic contrast-enhanced ultrasonography (DCE-US) has been used for evaluation of tumor response to antiangiogenic treatments. The objective of this study was to assess the link between DCE-US data obtained during the first week of treatment and subsequent tumor progression. Patients treated with antiangiogenic therapies were included in a multicentric prospective study from 2007 to 2010. DCE-US examinations were available at baseline and at day 7. For each examination, a 3 min perfusion curve was recorded just after injection of a contrast agent. Each perfusion curve was modeled with seven parameters. We analyzed the correlation between criteria measured up to day 7 on freedom from progression (FFP). The impact was assessed globally, according to tumor localization and to type of treatment. The median follow-up was 20 months. The mean transit time (MTT) evaluated at day 7 was the only criterion significantly associated with FFP (P = 0.002). The cut-off point maximizing the difference between FFP curves was 12 s. Patients with at least a 12 s MTT had a better FFP. The results according to tumor type were significantly heterogeneous: the impact of MTT on FFP was more marked for breast cancer (P = 0.004) and for colon cancer (P = 0.025) than for other tumor types. Similarly, the differences in FFP according to MTT at day 7 were marked (P = 0.004) in patients receiving bevacizumab. The MTT evaluated with DCE-US at day 7 is significantly correlated to FFP of patients treated with bevacizumab. This criterion might be linked to vascular normalization. 2007-A00399-44. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  20. Comparative vascular responses three months after paclitaxel and everolimus-eluting stent implantation in streptozotocin-induced diabetic porcine coronary arteries

    Directory of Open Access Journals (Sweden)

    Sheehy Alexander

    2012-06-01

    Full Text Available Abstract Background Diabetes remains a significant risk factor for restenosis/thrombosis following stenting. Although vascular healing responses following drug-eluting stent (DES treatment have been characterized previously in healthy animals, comparative assessments of different DES in a large animal model with isolated features of diabetes remains limited. We aimed to comparatively assess the vascular response to paclitaxel-eluting (PES and everolimus-eluting (EES stents in a porcine coronary model of streptozotocin (STZ-induced type I diabetes. Method Twelve Yucatan swine were induced hyperglycemic with a single STZ dose intravenously to ablate pancreatic β-cells. After two months, each animal received one XIENCE V® (EES and one Taxus Liberte (PES stent, respectively, in each coronary artery. After three months, vascular healing was assessed by angiography and histomorphometry. Comparative in vitro effects of everolimus and paclitaxel (10-5 M–10-12 M after 24 hours on carotid endothelial (EC and smooth muscle (SMC cell viability under hyperglycemic (42 mM conditions were assayed by ELISA. Caspase-3 fluorescent assay was used to quantify caspase-3 activity of EC treated with everolimus or paclitaxel (10-5 M, 10-7 M for 24 hours. Results After 3 months, EES reduced neointimal area (1.60 ± 0.41 mm, p vs. 0.08 ± 0.05, greater medial necrosis grade (0.52 ± 0.26 vs. 0.0 ± 0.0, and persistently elevated fibrin scores (1.60 ± 0.60 vs. 0.63 ± 0.41 with PES compared to EES (p In vitro, paclitaxel significantly increased (p -7 M, while everolimus did not affect EC/SMC apoptosis/necrosis within the dose range tested. In ECs, paclitaxel (10-5 M significantly increased caspase-3 activity (p  Conclusion After 3 months, both DES exhibited signs of delayed healing in a STZ-induced diabetic swine model. PES exhibited greater neointimal area, increased inflammation, greater medial necrosis, and

  1. Vascular Remodeling in Experimental Hypertension

    Directory of Open Access Journals (Sweden)

    Norma R. Risler

    2005-01-01

    Full Text Available The basic hemodynamic abnormality in hypertension is an increased peripheral resistance that is due mainly to a decreased vascular lumen derived from structural changes in the small arteries wall, named (as a whole vascular remodeling. The vascular wall is an active, flexible, and integrated organ made up of cellular (endothelial cells, smooth muscle cells, adventitia cells, and fibroblasts and noncellular (extracellular matrix components, which in a dynamic way change shape or number, or reorganize in response to physiological and pathological stimuli, maintaining the integrity of the vessel wall in physiological conditions or participating in the vascular changes in cardiovascular diseases such as hypertension. Research focused on new signaling pathways and molecules that can participate in the mechanisms of vascular remodeling has provided evidence showing that vascular structure is not only affected by blood pressure, but also by mechanisms that are independent of the increased pressure. This review will provide an overview of the evidence, explaining some of the pathophysiologic mechanisms participating in the development of the vascular remodeling, in experimental models of hypertension, with special reference to the findings in spontaneously hypertensive rats as a model of essential hypertension, and in fructose-fed rats as a model of secondary hypertension, in the context of the metabolic syndrome. The understanding of the mechanisms producing the vascular alterations will allow the development of novel pharmacological tools for vascular protection in hypertensive disease.

  2. IGF-1 deficiency in a critical period early in life influences the vascular aging phenotype in mice by altering miRNA-mediated post-transcriptional gene regulation: implications for the developmental origins of health and disease hypothesis.

    Science.gov (United States)

    Tarantini, Stefano; Giles, Cory B; Wren, Jonathan D; Ashpole, Nicole M; Valcarcel-Ares, M Noa; Wei, Jeanne Y; Sonntag, William E; Ungvari, Zoltan; Csiszar, Anna

    2016-08-01

    Epidemiological findings support the concept of Developmental Origins of Health and Disease, suggesting that early-life hormonal influences during a sensitive period of development have a fundamental impact on vascular health later in life. The endocrine changes that occur during development are highly conserved across mammalian species and include dramatic increases in circulating IGF-1 levels during adolescence. The present study was designed to characterize the effect of developmental IGF-1 deficiency on the vascular aging phenotype. To achieve that goal, early-onset endocrine IGF-1 deficiency was induced in mice by knockdown of IGF-1 in the liver using Cre-lox technology (Igf1 f/f mice crossed with mice expressing albumin-driven Cre recombinase). This model exhibits low-circulating IGF-1 levels during the peripubertal phase of development, which is critical for the biology of aging. Due to the emergence of miRNAs as important regulators of the vascular aging phenotype, the effect of early-life IGF-1 deficiency on miRNA expression profile in the aorta was examined in animals at 27 months of age. We found that developmental IGF-1 deficiency elicits persisting late-life changes in miRNA expression in the vasculature, which significantly differed from those in mice with adult-onset IGF-1 deficiency (TBG-Cre-AAV8-mediated knockdown of IGF-1 at 5 month of age in Igf1 f/f mice). Using a novel computational approach, we identified miRNA target genes that are co-expressed with IGF-1 and associate with aging and vascular pathophysiology. We found that among the predicted targets, the expression of multiple extracellular matrix-related genes, including collagen-encoding genes, were downregulated in mice with developmental IGF-1 deficiency. Collectively, IGF-1 deficiency during a critical period during early in life results in persistent changes in post-transcriptional miRNA-mediated control of genes critical targets for vascular health, which likely contribute to the

  3. The unsuitability of implantable Doppler probes for the early detection of renal vascular complications - a porcine model for prevention of renal transplant loss

    DEFF Research Database (Denmark)

    Amdisen, Chris; Jespersen, Bente; Møldrup, Ulla

    2017-01-01

    Abstract Background: Vascular occlusion is a rare, but serious complication after kidney transplantation often resulting in graft loss. We therefore aimed to develop an experimental porcine model for stepwise reduction of the renal venous blood flow and to compare an implantable Doppler probe...... and microdialysis for fast detection of vascular occlusion. Methods: In 20 pigs, implantable Doppler probes were placed on the renal artery and vein and a microdialysis catheter was placed in the renal cortex. An arterial flowprobe served as gold standard. Following two-hour baseline measurements, the pigs were....../3 (66%) reduction in renal blood flow. The implantable Doppler probe was not able to detect flow changes until there was total venous occlusion. Microdialysis detected changes in local metabolism after both arterial and venous occlusion; the implantable Doppler probe could only detect vascular...

  4. Differences in Blood Pressure and Vascular Responses Associated with Ambient Fine Particulate Matter Exposures Measured at the Personal Versus Community Level

    Science.gov (United States)

    Background Higher ambient fine particulate matter (PM2.5) levels can be associated with increased blood pressure and vascular dysfunction. Objectives To determine the differential effects on blood pressure and vascular function of daily changes in community ambient-...

  5. Patients with collagen vascular disease and dyspnea. The value of gallium scanning and bronchoalveolar lavage in predicting response to steroid therapy and clinical outcome

    International Nuclear Information System (INIS)

    Greene, N.B.; Solinger, A.M.; Baughman, R.P.

    1987-01-01

    Patients with collagen vascular disease with or without pulmonary symptoms were studied to determine the value of gallium scan and bronchoalveolar lavage (BAL) in predicting clinical outcome and response to steroid therapy. Thirty-six subjects, 20 with progressive dyspnea, were studied. Gallium uptake was seen in the lung in 17 of the 20 progressively dyspneic patient's and none of the 16 nonprogressive patients. The BAL fluid in the progressive patients had a higher percentage of neutrophils (13.4 percent +/- 2.88) and lymphocytes (16.1 percent +/- 2.75) than in the nonprogressive patients (neutrophils = 3.3 +/- 1.30 percent; lymphocytes = 5.6 +/- 1.57 percent. Of the 19 progressive patients who were treated with steroids or cyclophosphamide, six had only increased neutrophils in their BAL fluid and all died. The remaining 13 treated progressive patients had increased lymphocytes or a normal BAL (two patients): six had improvement in their vital capacity, six have had stable function, and one died. We found gallium scan and BAL useful in assessing progressive pulmonary fibrosis in collagen vascular disease

  6. Potential Responses of Vascular Plants from the Pristine "Lost World" of the Neotropical Guayana Highlands to Global Warming: Review and New Perspectives.

    Science.gov (United States)

    Rull, Valentí; Vegas-Vilarrúbia, Teresa

    2017-01-01

    The neotropical Guayana Highlands (GH) are one of the few remaining pristine environments on Earth, and they host amazing biodiversity with a high degree endemism, especially among vascular plants. Despite the lack of direct human disturbance, GH plants and their communities are threatened with extinction from habitat loss due to global warming (GW). Geographic information systems simulations involving the entire known vascular GH flora (>2430 species) predict potential GW-driven extinctions on the order of 80% by the end of this century, including nearly half of the endemic species. These estimates and the assessment of an environmental impact value for each species led to the hierarchization of plants by their risk of habitat loss and the definition of priority conservation categories. However, the predictions assume that all species will respond to GW by migrating upward and at equal rates, which is unlikely, so current estimates should be considered preliminary and incomplete (although they represent the best that can be done with the existing information). Other potential environmental forcings (i.e., precipitation shifts, an increase in the atmospheric CO 2 concentration) and idiosyncratic plant responses (i.e., resistance, phenotypic acclimation, rapid evolution) should also be considered, so detailed eco-physiological studies of the more threatened species are urgently needed. The main obstacles to developing such studies are the remoteness and inaccessibility of the GH and, especially, the difficulty in obtaining official permits for fieldwork.

  7. Potential Responses of Vascular Plants from the Pristine “Lost World” of the Neotropical Guayana Highlands to Global Warming: Review and New Perspectives

    Science.gov (United States)

    Rull, Valentí; Vegas-Vilarrúbia, Teresa

    2017-01-01

    The neotropical Guayana Highlands (GH) are one of the few remaining pristine environments on Earth, and they host amazing biodiversity with a high degree endemism, especially among vascular plants. Despite the lack of direct human disturbance, GH plants and their communities are threatened with extinction from habitat loss due to global warming (GW). Geographic information systems simulations involving the entire known vascular GH flora (>2430 species) predict potential GW-driven extinctions on the order of 80% by the end of this century, including nearly half of the endemic species. These estimates and the assessment of an environmental impact value for each species led to the hierarchization of plants by their risk of habitat loss and the definition of priority conservation categories. However, the predictions assume that all species will respond to GW by migrating upward and at equal rates, which is unlikely, so current estimates should be considered preliminary and incomplete (although they represent the best that can be done with the existing information). Other potential environmental forcings (i.e., precipitation shifts, an increase in the atmospheric CO2 concentration) and idiosyncratic plant responses (i.e., resistance, phenotypic acclimation, rapid evolution) should also be considered, so detailed eco-physiological studies of the more threatened species are urgently needed. The main obstacles to developing such studies are the remoteness and inaccessibility of the GH and, especially, the difficulty in obtaining official permits for fieldwork. PMID:28179913

  8. The Response of RIF-1 Fibrosarcomas to the Vascular-Disrupting Agent ZD6126 Assessed by In Vivo and Ex Vivo1H Magnetic Resonance Spectroscopy

    Directory of Open Access Journals (Sweden)

    Basetti Madhu

    2006-07-01

    Full Text Available The response of radiation-induced fibrosarcoma1 (RIF-1 tumors treated with the vascular-disrupting agent (VDA ZD6126 was assessed by in vivo and ex vivo1H magnetic resonance spectroscopy (MRS methods. Tumors treated with 200 mg/kg ZD6126 showed a significant reduction in total choline (tCho in vivo 24 hours after treatment, whereas control tumors showed a significant increase in tCho. This response was investigated further within both ex vivo unprocessed tumor tissues and tumor tissue metabolite extracts. Ex vivo high-resolution magic angle spinning (HRMAS and 1H MRS of metabolite extracts revealed a significant reduction in phosphocholine and glycerophosphocholine in biopsies of ZD6126-treated tumors, confirming in vivo tCho response. ZD6126-induced reduction in choline compounds is consistent with a reduction in cell membrane turnover associated with necrosis and cell death following disruption of the tumor vasculature. In vivo tumor tissue water diffusion and lactate measurements showed no significant changes in response to ZD6126. Spin-spin relaxation times (T2 of water and metabolites also remained unchanged. Noninvasive 1H MRS measurement of tCho in vivo provides a potential biomarker of tumor response to VDAs in RIF-1 tumors.

  9. The Vascular Pathogen Verticillium longisporum Does Not Affect Water Relations and Plant Responses to Drought Stress of Its Host, Brassica napus.

    Science.gov (United States)

    Lopisso, Daniel Teshome; Knüfer, Jessica; Koopmann, Birger; von Tiedemann, Andreas

    2017-04-01

    Verticillium longisporum is a host-specific vascular pathogen of oilseed rape (Brassica napus L.) that causes economic crop losses by impairing plant growth and inducing premature senescence. This study investigates whether plant damage through Verticillium stem striping is due to impaired plant water relations, whether V. longisporum affects responses of a susceptible B. napus variety to drought stress, and whether drought stress, in turn, affects plant responses to V. longisporum. Two-factorial experiments on a susceptible cultivar of B. napus infected or noninfected with V. longisporum and exposed to three watering levels (30, 60, and 100% field capacity) revealed that drought stress and V. longisporum impaired plant growth by entirely different mechanisms. Although both stresses similarly affected plant growth parameters (plant height, hypocotyl diameter, and shoot and root dry matter), infection of B. napus with V. longisporum did not affect any drought-related physiological or molecular genetic plant parameters, including transpiration rate, stomatal conductance, photosynthesis rate, water use efficiency, relative leaf water content, leaf proline content, or the expression of drought-responsive genes. Thus, this study provides comprehensive physiological and molecular genetic evidence explaining the lack of wilt symptoms in B. napus infected with V. longisporum. Likewise, drought tolerance of B. napus was unaffected by V. longisporum, as was the level of disease by drought conditions, thus excluding a concerted action of both stresses in the field. Although it is evident that drought and vascular infection with V. longisporum impair plant growth by different mechanisms, it remains to be determined by which other factors V. longisporum causes crop loss.

  10. FLT-PET for early response evaluation of colorectal cancer patients with liver metastases

    DEFF Research Database (Denmark)

    Mogensen, Marie Benzon; Loft, Annika; Aznar, Marianne

    2017-01-01

    BACKGROUND: Fluoro-L-thymidine (FLT) is a positron emission tomography/computed tomography (PET/CT) tracer which reflects proliferative activity in a cancer lesion. The main objective of this prospective explorative study was to evaluate whether FLT-PET can be used for the early evaluation...... standardised uptake values (SUVmax, SUVmean) were measured. After three cycles of chemotherapy, treatment response was assessed by CT scan based on RECIST 1.1. RESULTS: Thirty-nine consecutive patients were included of which 27 were evaluable. Dropout was mainly due to disease complications. Nineteen patients...... between the response according to RECIST and the early changes in FLT uptake measured as SUVmax(p = 0.24). CONCLUSIONS: No correlation was found between early changes in FLT uptake after the first cycle of treatment and the response evaluated from subsequent CT scans. It seems unlikely that FLT-PET can...

  11. Exposure to dim light at night during early development increases adult anxiety-like responses.

    Science.gov (United States)

    Borniger, Jeremy C; McHenry, Zachary D; Abi Salloum, Bachir A; Nelson, Randy J

    2014-06-22

    Early experiences produce effects that may persist throughout life. Therefore, to understand adult phenotype, it is important to investigate the role of early environmental stimuli in adult behavior and health. Artificial light at night (LAN) is an increasingly common phenomenon throughout the world. However, animals, including humans, evolved under dark night conditions. Many studies have revealed affective, immune, and metabolic alterations provoked by aberrant light exposure and subsequent circadian disruption. Pups are receptive to entraining cues from the mother and then light early during development, raising the possibility that the early life light environment may influence subsequent behavior. Thus, to investigate potential influences of early life exposure to LAN on adult phenotype, we exposed mice to dim (~5 lux; full spectrum white light) or dark (~0 lux) nights pre- and/or postnatally. After weaning at 3 weeks of age, all mice were maintained in dark nights until adulthood (9 weeks of age) when behavior was assessed. Mice exposed to dim light in early life increased anxiety-like behavior and fearful responses on the elevated plus maze and passive avoidance tests. These mice also displayed reduced growth rates, which ultimately normalized during adolescence. mRNA expression of brain derived neurotrophic factor (BDNF), a neurotrophin previously linked to early life environment and adult phenotype, was not altered in the prefrontal cortex or hippocampus by early life LAN exposure. Serum corticosterone concentrations were similar between groups at weaning, suggesting that early life LAN does not elicit a long-term physiologic stress response. Dim light exposure did not influence behavior on the open field, novel object, sucrose anhedonia, or forced swim tests. Our data highlight the potential deleterious consequences of low levels of light during early life to development and subsequent behavior. Whether these changes are due to altered maternal behavior

  12. Cytocompatibility and early inflammatory response of human endothelial cells in direct culture with Mg-Zn-Sr alloys

    Science.gov (United States)

    Cipriano, Aaron F.; Sallee, Amy; Tayoba, Myla; Cortez Alcaraz, Mayra C.; Lin, Alan; Guan, Ren-Guo; Zhao, Zhan-Yong; Liu, Huinan

    2018-01-01

    Crystalline Mg-Zinc (Zn)-Strontium (Sr) ternary alloys consist of elements naturally present in the human body and provide attractive mechanical and biodegradable properties for a variety of biomedical applications. The first objective of this study was to investigate the degradation and cytocompatibility of four Mg-4Zn-xSr alloys (x = 0.15, 0.5, 1.0, 1.5 wt%; designated as ZSr41A, B, C, and D respectively) in the direct culture with human umbilical vein endothelial cells (HUVEC) in vitro. The second objective was to investigate, for the first time, the early-stage inflammatory response in cultured HUVECs as indicated by the induction of vascular cellular adhesion molecule-1 (VCAM-1). The results showed that the 24-h in vitro degradation of the ZSr41 alloys containing a β-phase with a Zn/Sr at% ratio ~1.5 was significantly faster than the ZSr41 alloys with Zn/Sr at% ~1. Additionally, the adhesion density of HUVECs in the direct culture but not in direct contact with the ZSr41 alloys for up to 24 h was not adversely affected by the degradation of the alloys. Importantly, neither culture media supplemented with up to 27.6 mM Mg2+ ions nor media intentionally adjusted up to alkaline pH 9 induced any detectable adverse effects on HUVEC responses. In contrast, the significantly higher, yet non-cytotoxic, Zn2+ ion concentration from the degradation of ZSr41D alloy was likely the cause for the initially higher VCAM-1 expression on cultured HUVECs. Lastly, analysis of the HUVEC-ZSr41 interface showed near-complete absence of cell adhesion directly on the sample surface, most likely caused by either a high local alkalinity, change in surface topography, and/or surface composition. The direct culture method used in this study was proposed as a valuable tool for studying the design aspects of Zn-containing Mg-based biomaterials in vitro, in order to engineer solutions to address current shortcomings of Mg alloys for vascular device applications. PMID:27746360

  13. Advanced Maternal Age Worsens Postpartum Vascular Function

    Directory of Open Access Journals (Sweden)

    Jude S. Morton

    2017-06-01

    Full Text Available The age at which women experience their first pregnancy has increased throughout the decades. Pregnancy has an important influence on maternal short- and long-term cardiovascular outcomes. Pregnancy at an advanced maternal age increases maternal risk of gestational diabetes, preeclampsia, placenta previa and caesarian delivery; complications which predict worsened cardiovascular health in later years. Aging also independently increases the risk of cardiovascular disease; therefore, combined risk in women of advanced maternal age may lead to detrimental cardiovascular outcomes later in life. We hypothesized that pregnancy at an advanced maternal age would lead to postpartum vascular dysfunction. We used a reproductively aged rat model to investigate vascular function in never pregnant (virgin, previously pregnant (postpartum and previously mated but never delivered (nulliparous rats at approximately 13.5 months of age (3 months postpartum or equivalent. Nulliparous rats, in which pregnancy was spontaneously lost, demonstrated significantly reduced aortic relaxation responses (methylcholine [MCh] Emax: 54.2 ± 12.6% vs. virgin and postpartum rats (MCh Emax: 84.8 ± 3.5% and 84.7 ± 3.2% respectively; suggesting pregnancy loss causes a worsened vascular pathology. Oxidized LDL reduced relaxation to MCh in aorta from virgin and postpartum, but not nulliparous rats, with an increased contribution of the LOX-1 receptor in the postpartum group. Further, in mesenteric arteries from postpartum rats, endothelium-derived hyperpolarization (EDH-mediated vasodilation was reduced and a constrictive prostaglandin effect was apparent. In conclusion, aged postpartum rats exhibited vascular dysfunction, while rats which had pregnancy loss demonstrated a distinct vascular pathology. These data demonstrate mechanisms which may lead to worsened outcomes at an advanced maternal age; including early pregnancy loss and later life cardiovascular dysfunction.

  14. Hass avocado modulates postprandial vascular reactivity and postprandial inflammatory responses to a hamburger meal in healthy volunteers.

    Science.gov (United States)

    Li, Zhaoping; Wong, Angela; Henning, Susanne M; Zhang, Yanjun; Jones, Alexis; Zerlin, Alona; Thames, Gail; Bowerman, Susan; Tseng, Chi-Hong; Heber, David

    2013-02-26

    Hass avocados are rich in monounsaturated fatty acids (oleic acid) and antioxidants (carotenoids, tocopherols, polyphenols) and are often eaten as a slice in a sandwich containing hamburger or other meats. Hamburger meat forms lipid peroxides during cooking. After ingestion, the stomach functions as a bioreactor generating additional lipid peroxides and this process can be inhibited when antioxidants are ingested together with the meat. The present pilot study was conducted to investigate the postprandial effect of the addition of 68 g of avocado to a hamburger on vasodilation and inflammation. Eleven healthy subjects on two separate occasions consumed either a 250 g hamburger patty alone (ca. 436 cal and 25 g fat) or together with 68 grams of avocado flesh (an additional 114 cal and 11 g of fat for a total of 550 cal and 36 g fat), a common culinary combination, to assess effects on vascular health. Using the standard peripheral arterial tonometry (PAT) method to calculate the PAT index, we observed significant vasoconstriction 2 hours following hamburger ingestion (2.19 ± 0.36 vs. 1.56 ± 0.21, p = 0.0007), which did not occur when the avocado flesh was ingested together with the burger (2.17 ± 0.57 vs. 2.08 ± 0.51, NS p = 0.68). Peripheral blood mononuclear cells were isolated from postprandial blood samples and the Ikappa-B alpha (IκBα) protein concentration was determined to assess effects on inflammation. At 3 hours, there was a significant preservation of IκBα (131% vs. 58%, p = 0.03) when avocado was consumed with the meat compared to meat alone, consistent with reduced activation of the NF-kappa B (NFκB) inflammatory pathway. IL-6 increased significantly at 4 hours in postprandial serum after consumption of the hamburger, but no change was observed when avocado was added. Postprandial serum triglyceride concentration increased, but did not further increase when avocado was ingested with the burger compared to burger alone despite the added fat and

  15. [Inflammasome and its role in immunological and inflammatory response at early stage of burns].

    Science.gov (United States)

    Zhang, Fang; Li, Jiahui; Xia, Zhaofan

    2014-06-01

    Inflammasomes are large multi-protein complexes that serve as a platform for caspase-1 activation, and this process induces subsequent maturation and secretion of the proinflammatory cytokines IL-1β and IL-18, as well as pyroptosis. As an important component of the innate immune system, early activation of inflammasomes in a variety of immune cell subsets can mediate inflammatory response and immunological conditions after burn injury. Here, we review the current knowledge of inflammasomes and its role in immunological and inflammatory response at the early stage of burn injury.

  16. Vascular pattern of the spontaneous C3H mouse mammary carcinoma and its significance in radiation response and in hyperthermia

    Energy Technology Data Exchange (ETDEWEB)

    Falk, P [Hammersmith Hospital, London (UK). M.R.C. Cyclotron Unit

    1980-02-01

    This study showed that the vascular pattern of the spontaneous C3H mouse mammary carcinoma develops from a capillary network into an afferent system lacking arterioles and consisting only of capillary-like vessels and an efferent system characterized by large sinuses. Lack of correlation between the growth of stroma and parenchyma leads to a circuitous and uneven supply of blood and to a high degree of occlusion of the efferent system with consequent reduction in the rate of flow of blood. The parenchyma consists of tubules formed of single or multiple layers of cells between which capillaries do not penetrate. The diffusion pathway of oxygen and nutrients to the inner cells of the multi-layered tubules is considerably longer than that to their outer cells or to the cells of the single-layered tubules. Consequently it is in the former parts that anoxia and severe hypoxia are likely to prevail. The pattern of necrosis agrees with this supposition. It is predicted that radiation hyperthermia will act differentially and in opposite senses on these two tumour components, hyperthermia being more effective on the former, radiation on the latter.

  17. Use of placental vascularization indices and uterine artery peak systolic velocity in early detection of pregnancies complicated by gestational diabetes, chronic or gestational hypertension, and preeclampsia at risk.

    Science.gov (United States)

    Altorjay, Ábel T; Surányi, Andrea; Nyári, Tibor; Németh, Gábor

    2017-04-14

    We aimed to investigate correlations between uterine artery peak systolic velocity (AUtPSV), and placental vascularization in groups of normal blood pressure (NBP) and hypertensive disorders of pregnancy (chronic hypertension (CHT), gestational hypertension (GHT) and preeclampsia (PE)) alone or in combination with gestational diabetes mellitus (GDM), and hypothesized that AUtPSV rises when GDM complicates pregnancy hypertension. Placental 3-dimensional power Doppler indices, such as vascularization index (VI), flow index (FI), and vascularization-flow index (VFI), and uterine artery peak systolic velocity (AUtPSV) were measured in CHT (N=43), CHT+GDM (N=15), GHT (N=57), GHT+GDM (N=23) and PE (N=17) pregnancies, and compared to NBP (N=109). Correlations were analyzed between vascularization indices, AUtPSV, pregestational BMI and adverse pregnancy outcome rates. In our results VI was higher in CHT (P=0.010), while FI was lower in CHT (P=0.009), GHT and PE (P=0.001) compared to NBP. In case of VFI, significant difference was found between CHT and GHT (P=0.002), and NBP and PE (P=0.001). FI was found prognostic for umbilical pH and neonatal birth weight. Pre-gestational BMI was significantly higher in GHT+GDM compared to GHT, and in CHT+GDM compared to the CHT group. As for AUtPSV, significant difference was found between NBP and CHT (P=0.012), NBP and CHT+GDM (P=0.045), NBP and GHT+GDM (P=0.007), NBP and PE (P=0.032), and GHT and GHT+GDM (P=0.048) groups. Our study revealed that vascularization indices and AUtPSV show significant differences due to gestational pathology, and can be useful in detection of pregnancies at risk.

  18. Vascular ultrasound.

    Science.gov (United States)

    Pilcher, D B; Ricci, M A

    1998-04-01

    Surgeon-interpreted diagnostic ultrasound has become the preferred screening test and often the definitive test for the diagnosis of arterial stenosis, aneurysm, and venous thrombosis. As a modality for surveillance, its noninvasive quality makes it particularly appealing as the test of choice to screen patients for abdominal aortic aneurysms or to perform follow-up examinations on those patients with a carotid endartectomy or in situ bypass grafts. The increasing reliance on intraoperative duplex imaging of vascular procedures demands that the surgeon learn the skills to perform the studies without a technologist or radiologist to interpret the examination.

  19. Early Change in Stroke Size Performs Best in Predicting Response to Therapy.

    Science.gov (United States)

    Simpkins, Alexis Nétis; Dias, Christian; Norato, Gina; Kim, Eunhee; Leigh, Richard

    2017-01-01

    Reliable imaging biomarkers of response to therapy in acute stroke are needed. The final infarct volume and percent of early reperfusion have been used for this purpose. Early fluctuation in stroke size is a recognized phenomenon, but its utility as a biomarker for response to therapy has not been established. This study examined the clinical relevance of early change in stroke volume and compared it with the final infarct volume and percent of early reperfusion in identifying early neurologic improvement (ENI). Acute stroke patients, enrolled between 2013 and 2014 with serial magnetic resonance imaging (MRI) scans (pretreatment baseline, 2 h post, and 24 h post), who received thrombolysis were included in the analysis. Early change in stroke volume, infarct volume at 24 h on diffusion, and percent of early reperfusion were calculated from the baseline and 2 h MRI scans were compared. ENI was defined as ≥4 point decrease in National Institutes of Health Stroke Scales within 24 h. Logistic regression models and receiver operator characteristics analysis were used to compare the efficacy of 3 imaging biomarkers. Serial MRIs of 58 acute stroke patients were analyzed. Early change in stroke volume was significantly associated with ENI by logistic regression analysis (OR 0.93, p = 0.048) and remained significant after controlling for stroke size and severity (OR 0.90, p = 0.032). Thus, for every 1 mL increase in stroke volume, there was a 10% decrease in the odds of ENI, while for every 1 mL decrease in stroke volume, there was a 10% increase in the odds of ENI. Neither infarct volume at 24 h nor percent of early reperfusion were significantly associated with ENI by logistic regression. Receiver-operator characteristic analysis identified early change in stroke volume as the only biomarker of the 3 that performed significantly different than chance (p = 0.03). Early fluctuations in stroke size may represent a more reliable biomarker for response to therapy than the

  20. Auditory-neurophysiological responses to speech during early childhood: Effects of background noise.

    Science.gov (United States)

    White-Schwoch, Travis; Davies, Evan C; Thompson, Elaine C; Woodruff Carr, Kali; Nicol, Trent; Bradlow, Ann R; Kraus, Nina

    2015-10-01

    Early childhood is a critical period of auditory learning, during which children are constantly mapping sounds to meaning. But this auditory learning rarely occurs in ideal listening conditions-children are forced to listen against a relentless din. This background noise degrades the neural coding of these critical sounds, in turn interfering with auditory learning. Despite the importance of robust and reliable auditory processing during early childhood, little is known about the neurophysiology underlying speech processing in children so young. To better understand the physiological constraints these adverse listening scenarios impose on speech sound coding during early childhood, auditory-neurophysiological responses were elicited to a consonant-vowel syllable in quiet and background noise in a cohort of typically-developing preschoolers (ages 3-5 yr). Overall, responses were degraded in noise: they were smaller, less stable across trials, slower, and there was poorer coding of spectral content and the temporal envelope. These effects were exacerbated in response to the consonant transition relative to the vowel, suggesting that the neural coding of spectrotemporally-dynamic speech features is more tenuous in noise than the coding of static features-even in children this young. Neural coding of speech temporal fine structure, however, was more resilient to the addition of background noise than coding of temporal envelope information. Taken together, these results demonstrate that noise places a neurophysiological constraint on speech processing during early childhood by causing a breakdown in neural processing of speech acoustics. These results may explain why some listeners have inordinate difficulties understanding speech in noise. Speech-elicited auditory-neurophysiological responses offer objective insight into listening skills during early childhood by reflecting the integrity of neural coding in quiet and noise; this paper documents typical response

  1. Early-Life Persistent Vitamin D Deficiency Alters Cardiopulmonary Responses to Particulate Matter-Enhanced Atmospheric Smog in Adult Mice

    Science.gov (United States)

    This study demonstrates that early-life persistent vitamin D deficiency alters the cardiopulmonary response to smog in mice and may increase risk of adverse effects. Early life nutritional deficiencies can lead to increased cardiovascular susceptibility to environme...

  2. [The future of vascular medicine].

    Science.gov (United States)

    Kroeger, K; Luther, B

    2014-10-01

    In the future vascular medicine will still have a great impact on health of people. It should be noted that the aging of the population does not lead to a dramatic increase in patient numbers, but will be associated with a changing spectrum of co-morbidities. In addition, vascular medical research has to include the intensive care special features of vascular patients, the involvement of vascular medicine in a holistic concept of fast-track surgery, a geriatric-oriented intensive monitoring and early geriatric rehabilitation. For the future acceptance of vascular medicine as a separate subject area under delimitation of cardiology and radiology is important. On the other hand, the subject is so complex and will become more complex in future specialisations that mixing of surgery and angiology is desirable, with the aim to preserve the vascular surgical knowledge and skills on par with the medical and interventional measures and further develop them. Only large, interdisciplinary guided vascular centres will be able to provide timely diagnosis and therapy, to deal with the growing multi-morbidity of the patient, to perform complex therapies even in an acute emergency and due to sufficient number of cases to present with well-trained and experienced teams. These requirements are mandatory to decrease patients' mortality step by step. Georg Thieme Verlag KG Stuttgart · New York.

  3. Tissue factor-dependent vascular endothelial growth factor production by human fibroblasts in response to activated factor VII.

    Science.gov (United States)

    Ollivier, V; Bentolila, S; Chabbat, J; Hakim, J; de Prost, D

    1998-04-15

    The transmembrane protein tissue factor (TF) is the cell surface receptor for coagulation factor VII (FVII) and activated factor VII (FVIIa). Recently, TF has been identified as a regulator of angiogenesis, tumor growth, and metastasis. This study was designed to link the binding of FVII(a) to its receptor, TF, with the subsequent triggering of angiogenesis through vascular endothelial growth factor (VEGF) production by human lung fibroblasts. We report that incubation of fibroblasts, which express constitutive surface TF, with FVII(a) induces VEGF synthesis. FVII(a)-induced VEGF secretion, assessed by a specific enzyme-linked immunosorbent assay, was time- and concentration-dependent. VEGF secretion was maximal after 24 hours of incubation of the cells with 100 nmol/L FVII(a) and represented a threefold induction of the basal VEGF level. Reverse transcriptase-polymerase chain reaction analysis of VEGF detected three mRNA species of 180, 312, and 384 bp corresponding, respectively, to VEGF121, VEGF165, and VEGF189. A 2.5- to 3.5-fold increase was observed for the 180- and 312-bp transcripts at 12 and 24 hours, respectively. FVII(a)-dependent VEGF production was inhibited by a pool of antibodies against TF, pointing to the involvement of this receptor. On specific active-site inhibition with dansyl-glutamyl-glycinyl-arginyl chloromethyl ketone, FVIIa lost 70% of its capacity to elicit VEGF production. Consistent with this, the native form (zymogen) of FVII only had a 1.8-fold stimulating effect. Protein tyrosine kinase and protein kinase C are involved in signal transduction leading to VEGF production, as shown by the inhibitory effects of genistein and GF 109203X. The results of this study indicate that TF is essential for VIIa-induced VEGF production by human fibroblasts and that its role is mainly linked to the proteolytic activity of the TF-VIIa complex.

  4. Time to failure and neuromuscular response to intermittent isometric exercise at different levels of vascular occlusion: a randomized crossover study

    Directory of Open Access Journals (Sweden)

    Mikhail Santos Cerqueira

    2017-04-01

    Full Text Available Objectives: The purpose this study was investigate the effects of different vascular occlusion levels (total occlusion (TO, partial occlusion (PO or free flow (FF during intermittent isometric handgrip exercise (IIHE on the time to failure (TF and the recovery of the maximum voluntary isometric force (MVIF, median frequency (EMGFmed and peak of EMG signal (EMGpeak after failure.  Methods: Thirteen healthy men (21 ± 1.71 year carried out an IIHE until the failure at 45% of MVIF with TO, PO or FF. Occlusion pressure was determined previously to the exercise. The MVIF, EMGFmed and EMGpeak were measured before and after exercise. Results: TF (in seconds was significantly different (p < 0.05 among all investigated conditions: TO (150 ± 68, PO (390 ± 210 and FF (510 ± 240. The MVIF was lower immediately after IIHE, remaining lower eleven minutes after failure in all cases (p <0.05, when compared to pre exercise. There was a greater force reduction (p <0.05 one minute after the failure in the PO (-45.8% and FF (-39.9% conditions, when compared to TO (-28.1%. Only the PO condition caused lower MVIF (p <0.05 than in the OT, eleven minutes after the task failure. PO caused a greater reduction in EMGFmed compared TO and greater increase in EMGpeak, when compared to TO and FF (p <0.05. Conclusions: TO during IIHE lead to a lower time to failure, but a faster MVIF recovery, while the PO seems to be associated to a slower neuromuscular recovery, when compared to other conditions.

  5. Effect of altered arterial perfusion pressure on vascular conductance and muscle blood flow dynamic response during exercise in humans.

    Science.gov (United States)

    Villar, Rodrigo; Hughson, Richard L

    2013-03-01

    Changes in vascular conductance (VC) are required to counter changes in muscle perfusion pressure (MPP) to maintain muscle blood flow (MBF) during exercise. We investigated the recruitment of VC as a function of peak VC measured in three body positions at two different work rates to test the hypothesis that adaptations in VC compensated changes in MPP at low-power output (LPO), but not at high-power output (HPO). Eleven healthy volunteers exercised at LPO and HPO (repeated plantar flexion contractions at 20-30% maximal voluntary contraction, respectively) in horizontal (HOR), 35° head-down tilt (HDT), and 45° head-up tilt (HUT). Muscle blood flow velocity and popliteal diameter were measured by ultrasound to determine MBF, and VC was estimated by dividing MBF flow by MPP. Peak VC was unaffected by body position. The rates of increase in MBF and VC were significantly faster in HUT and slower in HDT than HOR, and rates were faster in LPO than HPO. During LPO exercise, the increase in, and steady-state values of, MBF were less for HUT and HDT than HOR; the increase in VC was less in HUT than HOR and HDT. During HPO exercise, MBF in the HDT was reduced compared with HOR and HUT, even though VC reached 92% VC peak, which was greater than HOR, which was, in turn, greater than HUT. Reduced MBF during HPO HDT exercise had the functional consequence of a significant increase in muscle electromyographic index, revealing the effects of MPP on O2 delivery during exercise.

  6. Peripheral vascular response to mild indirect cooling in patients with homozygous sickle cell (SS) disease and the frequency of painful crisis.

    Science.gov (United States)

    Mohan, J; Marshall, J M; Reid, H L; Thomas, P W; Hambleton, I; Serjeant, G R

    1998-02-01

    1. In homozygous sickle cell (SS) disease, skin cooling is a common precipitating factor of the painful crisis which is associated with avascular necrosis of active bone marrow. Since skin cooling does not directly induce sickling, we have investigated the nature of the reflex vascular responses to mild cooling in SS patients in a steady state of the disease and compared them with their history of painful crises. 2. Experiments were performed in Jamaica on 60 male SS patients and 30 matched control subjects with normal haemoglobin (AA) genotype. Forearm blood flow (FBF) was measured by venous occlusion plethysmography and mean arterial pressure (MAP) by a Finapres device: forearm vascular resistance (FVR) was calculated as MAP/FBF. Cutaneous erythrocyte flux in forearm and hand was monitored by a laser Doppler meter. The contralateral hand was immersed in cool water at 16 degrees C for 2 min, 6 times, at random intervals of 0.5-3 min. 3. The first cool immersion evoked an increase in MAP, cutaneous vasoconstriction and a net increase in FVR in both AA and SS subjects. However, the direction of change in FVR varied between individuals such that 18 AA subjects showed an increase in FVR (constrictor group) while 12 showed a decrease in FVR, indicating vasodilatation in forearm muscle (dilator group). In contrast, 50 SS subjects showed an increase in FVR and only 10 showed a decrease in FVR. The proportion of subjects who showed net vasoconstriction was significantly greater in the SS than in the AA group (83% versus 60%, P = 0.03, chi 2 test). 4. By the sixth cool stimulus, the 'dilator' group of AA subjects showed no change in FVR while the 'dilator' group of SS patients showed an increase in FVR. We suggest that forearm muscle vasodilatation was the characteristic component of the alerting/defence response to novel or noxious stimuli which habituates on repetition. 5. In the whole group of SS patients, baseline values of cutaneous vascular resistance and FVR

  7. Early positron emission tomography response-adapted treatment in stage I and II hodgkin lymphoma

    DEFF Research Database (Denmark)

    André, Marc P.E.; Girinsky, Théodore; Federico, Massimo

    2017-01-01

    Purpose Patients who receive combined modality treatment for stage I and II Hodgkin lymphoma (HL) have an excellent outcome. Early response evaluation with positron emission tomography (PET) scan may improve selection of patients who need reduced or more intensive treatments. Methods We performed...

  8. Transcriptional response of bronchial epithelial cells to Pseudomonas aeruginosa: identification of early mediators of host defense.

    NARCIS (Netherlands)

    Vos, J.B.; Sterkenburg, M.A. van; Rabe, K.F.; Schalkwijk, J.; Hiemstra, P.S.; Datson, N.A.

    2005-01-01

    The airway epithelium responds to microbial exposure by altering expression of a variety of genes to increase innate host defense. We aimed to delineate the early transcriptional response in human primary bronchial epithelial cells exposed for 6 h to a mixture of IL-1beta and TNF-alpha or

  9. Computed tomography assessment of early response to neoadjuvant therapy in colon cancer

    DEFF Research Database (Denmark)

    Dam, Claus; Lund-Rasmussen, Vera; Pløen, John

    2015-01-01

    INTRODUCTION: Using multidetector computed tomography, we aimed to assess the early response of neoadjuvant drug therapy for locally advanced colon cancer. METHODS: Computed tomography with IV contrast was acquired from 67 patients before and after up to three cycles of preoperative treatment. All...

  10. Early pathogenesis and inflammatory response in experimental bovine mastitis due to Streptococcus uberis

    DEFF Research Database (Denmark)

    Pedersen, L.H.; Aalbæk, B.; Røntved, C.M.

    2003-01-01

    A generally similar clinical response was observed in six lactating Holstein-Friesian cows after intramammary inoculation with approximately 107 colony-forming units of Streptococcus uberis. Increased concentrations of serum amyloid A (SAA) were measured in both milk and serum taken 6 and 11 h af...... proteins as potential diagnostic markers for the early detection of S. uberis-associated mastitis....

  11. Early Detection Rapid Response Program Targets New Noxious Weed Species in Washington State

    Science.gov (United States)

    Andreas, Jennifer E.; Halpern, Alison D.; DesCamp, Wendy C.; Miller, Timothy W.

    2015-01-01

    Early detection, rapid response is a critical component of invasive plant management. It can be challenging, however, to detect new invaders before they become established if landowners cannot identify species of concern. In order to increase awareness, eye-catching postcards were developed in Washington State as part of a noxious weed educational…

  12. Early Prediction and Evaluation of Breast Cancer Response to Neoadjuvant Chemotherapy Using Quantitative DCE-MRI

    Directory of Open Access Journals (Sweden)

    Alina Tudorica

    2016-02-01

    Full Text Available The purpose is to compare quantitative dynamic contrast-enhanced (DCE magnetic resonance imaging (MRI metrics with imaging tumor size for early prediction of breast cancer response to neoadjuvant chemotherapy (NACT and evaluation of residual cancer burden (RCB. Twenty-eight patients with 29 primary breast tumors underwent DCE-MRI exams before, after one cycle of, at midpoint of, and after NACT. MRI tumor size in the longest diameter (LD was measured according to the RECIST (Response Evaluation Criteria In Solid Tumors guidelines. Pharmacokinetic analyses of DCE-MRI data were performed with the standard Tofts and Shutter-Speed models (TM and SSM. After one NACT cycle the percent changes of DCE-MRI parameters Ktrans (contrast agent plasma/interstitium transfer rate constant, ve (extravascular and extracellular volume fraction, kep (intravasation rate constant, and SSM-unique τi (mean intracellular water lifetime are good to excellent early predictors of pathologic complete response (pCR vs. non-pCR, with univariate logistic regression C statistics value in the range of 0.804 to 0.967. ve values after one cycle and at NACT midpoint are also good predictors of response, with C ranging 0.845 to 0.897. However, RECIST LD changes are poor predictors with C = 0.609 and 0.673, respectively. Post-NACT Ktrans, τi, and RECIST LD show statistically significant (P < .05 correlations with RCB. The performances of TM and SSM analyses for early prediction of response and RCB evaluation are comparable. In conclusion, quantitative DCE-MRI parameters are superior to imaging tumor size for early prediction of therapy response. Both TM and SSM analyses are effective for therapy response evaluation. However, the τi parameter derived only with SSM analysis allows the unique opportunity to potentially quantify therapy-induced changes in tumor energetic metabolism.

  13. [Health threats and health system crises. An approach to early warning and response. 2008 SESPAS Report].

    Science.gov (United States)

    Simón Soria, Fernando; Guillén Enríquez, Francisco Javier

    2008-04-01

    The world is changing more and faster than ever before. New diseases are coming to light each year, controlled diseases are reemerging as potential threats, and natural or man-made disasters are increasingly affecting human health. The "International Health Regulations (2005)" reflect the changes in the response of public health to this new situation. Surveillance of specific diseases and predefined control measures have been replaced by surveillance of public health events of international concern and control measures adapted to each situation. The public health events of international interest are characterized by their seriousness, predictability, the risk of international spread and potential for travel or trade restrictions. The development of the European Early Warning and Response System in 1998 and the creation of the European Center for Disease Prevention and Control in 2005 demonstrate political commitment in Europe, with early detection of and response to public health threats. However, timely risk evaluation and response at a national level requires improved data digitalization and accessibility, automatic notification processes, data analysis and dissemination of information, the combination of information from multiple sources and adaptation of public health services. The autonomous regions in Spain are initiating this adaptation process, but interoperability between systems and the development of guidelines for a coordinated response should be steered by the National Interregional Health Council and coordinated by the Ministry of Health. Efficient early warning systems of health threats that allow for a timely response and reduce uncertainty about information would help to minimize the risk of public health crises. The profile of public health threats is nonspecific. Early detection of threats requires access to information from multiple sources and efficient risk assessment. Key factors for improving the response to public health threats are the

  14. Abnormal early brain responses during visual search are evident in schizophrenia but not bipolar affective disorder.

    Science.gov (United States)

    VanMeerten, Nicolaas J; Dubke, Rachel E; Stanwyck, John J; Kang, Seung Suk; Sponheim, Scott R

    2016-01-01

    People with schizophrenia show deficits in processing visual stimuli but neural abnormalities underlying the deficits are unclear and it is unknown whether such functional brain abnormalities are present in other severe mental disorders or in individuals who carry genetic liability for schizophrenia. To better characterize brain responses underlying visual search deficits and test their specificity to schizophrenia we gathered behavioral and electrophysiological responses during visual search (i.e., Span of Apprehension [SOA] task) from 38 people with schizophrenia, 31 people with bipolar disorder, 58 biological relatives of people with schizophrenia, 37 biological relatives of people with bipolar disorder, and 65 non-psychiatric control participants. Through subtracting neural responses associated with purely sensory aspects of the stimuli we found that people with schizophrenia exhibited reduced early posterior task-related neural responses (i.e., Span Endogenous Negativity [SEN]) while other groups showed normative responses. People with schizophrenia exhibited longer reaction times than controls during visual search but nearly identical accuracy. Those individuals with schizophrenia who had larger SENs performed more efficiently (i.e., shorter reaction times) on the SOA task suggesting that modulation of early visual cortical responses facilitated their visual search. People with schizophrenia also exhibited a diminished P300 response compared to other groups. Unaffected first-degree relatives of people with bipolar disorder and schizophrenia showed an amplified N1 response over posterior brain regions in comparison to other groups. Diminished early posterior brain responses are associated with impaired visual search in schizophrenia and appear to be specifically associated with the neuropathology of schizophrenia. Published by Elsevier B.V.

  15. Early host response in the mammary gland after experimental Streptococcus uberis challenge in heifers.

    Science.gov (United States)

    de Greeff, Astrid; Zadoks, Ruth; Ruuls, Lisette; Toussaint, Mathilda; Nguyen, Thi Kim Anh; Downing, Alison; Rebel, Johanna; Stockhofe-Zurwieden, Norbert; Smith, Hilde

    2013-06-01

    Streptococcus uberis is a highly prevalent causative agent of bovine mastitis, which leads to large economic losses in the dairy industry. The aim of this study was to examine the host response during acute inflammation after experimental challenge with capsulated Strep. uberis. Gene expression in response to Strep. uberis was compared between infected and control quarters in 3 animals. All quarters (n=16) were sampled at 16 different locations. Microarray data showed that 239 genes were differentially expressed between infected and control quarters. No differences in gene expression were observed between the different locations. Microarray data were confirmed for several genes using quantitative PCR analysis. Genes differentially expressed due to early Strep. uberis mastitis represented several stages of the process of infection: (1) pathogen recognition; (2) chemoattraction of neutrophils; (3) tissue repair mechanisms; and (4) bactericidal activity. Three different pathogen recognition genes were induced: ficolins, lipopolysaccharide binding protein, and toll-like receptor 2. Calgranulins were found to be the most strongly upregulated genes during early inflammation. By histology and immunohistochemistry, we demonstrated that changes in gene expression in response to Strep. uberis were induced both in infiltrating somatic milk cells and in mammary epithelial cells, demonstrating that the latter cell type plays a role in milk production as well as immune responsiveness. Given the rapid development of inflammation or mastitis after infection, early diagnosis of (Strep. uberis) mastitis is required for prevention of disease and spread of the pathogen. Insight into host responses could help to design immunomodulatory therapies to dampen inflammation after (early) diagnosis of Strep. uberis mastitis. Future research should focus on development of these early diagnostics and immunomodulatory components for mastitis treatment. Copyright © 2013 American Dairy Science

  16. Vascular lumen formation.

    Science.gov (United States)

    Lammert, Eckhard; Axnick, Jennifer

    2012-04-01

    The vascular system developed early in evolution. It is required in large multicellular organisms for the transport of nutrients, oxygen, and waste products to and from tissues. The vascular system is composed of hollow tubes, which have a high level of complexity in vertebrates. Vasculogenesis describes the de novo formation of blood vessels, e.g., aorta formation in vertebrate embryogenesis. In contrast, angiogenesis is the formation of blood vessels from preexisting ones, e.g., sprouting of intersomitic blood vessels from the aorta. Importantly, the lumen of all blood vessels in vertebrates is lined and formed by endothelial cells. In both vasculogenesis and angiogenesis, lumen formation takes place in a cord of endothelial cells. It involves a complex molecular mechanism composed of endothelial cell repulsion at the cell-cell contacts within the endothelial cell cords, junctional rearrangement, and endothelial cell shape change. As the vascular system also participates in the course of many diseases, such as cancer, stroke, and myocardial infarction, it is important to understand and make use of the molecular mechanisms of blood vessel formation to better understand and manipulate the pathomechanisms involved.

  17. The effect of ghrelin upon the early immune response in lean and obese mice during sepsis.

    Directory of Open Access Journals (Sweden)

    Daniel Siegl

    Full Text Available It is well established that obesity-related hormones can have modulatory effects associated with the immune response. Ghrelin, a hormone mainly derived from endocrine cells of the gastric mucosa, regulates appetite, energy expenditure and body weight counteracting leptin, a hormone mainly derived from adipocytes. Additionally, receptors of both have been detected on immune cells and demonstrated an immune regulatory function during sepsis.In the present study, the effect of peripheral ghrelin administration on early immune response and survival was investigated with lean mice and mice with diet-induced obesity using cecal ligation and puncture to induce sepsis.In the obese group, we found that ghrelin treatment improved survival, ameliorated hypothermia, and increased hyperleptinemia as compared to the lean controls. We also observed that ghrelin treatment divergently regulated serum IL-1ß and TNF-α concentrations in both lean and obese septic mice. Ghrelin treatment initially decreased but later resulted in increased bacteriaemia in lean mice while having no impact upon obese mice. Similarly, ghrelin treatment increased early neutrophil oxidative burst while causing a decrease 48 hours after sepsis inducement.In conclusion, as the immune response to sepsis temporally changes, ghrelin treatment differentially mediates this response. Specifically, we observed that ghrelin conferred protective effects during the early phase of sepsis, but during the later phase deteriorated immune response and outcome. These adverse effects were more pronounced upon lean mice as compared to obese mice.

  18. Early lactation feed intake and milk yield responses of dairy cows offered grass silages harvested at early maturity stages

    DEFF Research Database (Denmark)

    Randby, A T; Weisbjerg, M R; Nørgaard, P

    2012-01-01

    was available in automatic feed stations. Intake of grass silage when fed as the sole feed was 16.9 kg of DM on average for lactation wk 1 to 16. When H1 was supplemented with 4 or 8 kg of concentrates, silage DM intake did not change, but total DM intake increased to 20.6 and 23.7 kg/d, respectively. Energy......The main objective was to evaluate the potential of grass silages of very high quality to support a high milk yield with a low or moderate, or even without concentrate supplementation. Production responses to increased levels of concentrate supplementation with 3 primary growth grass silages...... differing in digestibility were studied using 66 Norwegian Red dairy cows. Roundbale silage was produced from a timothy-dominated sward at very early (H1), early (H2), and normal (H3) stages of crop maturity. Crops were rapidly wilted (h) and a formic acid-based additive was applied. All silages were...

  19. Acute response of circulating vascular regulating microRNAs during and after high-intensity and high-volume cycling in children

    Directory of Open Access Journals (Sweden)

    Yvonne eKilian

    2016-03-01

    Full Text Available Aim: The aim of the present study was to analyze the response of vascular circulating microRNAs (miRNAs; miR-16, miR-21, miR-126 and the VEGF mRNA following an acute bout of HIIT and HVT in children. Methods: Twelve healthy competitive young male cyclists (14.4 ± 0.8 yrs; 57.9 ± 9.4 ml·min-1·kg-1 peak oxygen uptake performed one session of high intensity 4x4 min intervals (HIIT at 90-95% peak power output, each interval separated by 3 min of active recovery, and one high volume session (HVT consisting of a constant load exercise for 90 min at 60% peak power output. Capillary blood from the earlobe was collected under resting conditions, during exercise (d1 = 20 min, d2 = 30 min, d3 = 60 min, and 0, 30, 60, 180 min after the exercise to determine miR-16, -21, -126 and VEGF mRNA.Results: HVT significantly increased miR-16 and miR-126 during and after the exercise compared to pre values, whereas HIIT showed no significant influence on the miRNAs compared to pre values. VEGF mRNA significantly increased during and after HIIT (d1, 30`, 60`, 180` and HVT (d3, 0`, 60`. Conclusion: Results of the present investigation suggest a volume dependent exercise regulation of vascular regulating miRNAs (miR-16, miR-21, miR-126 in children. In line with previous data, our data show that acute exercise can alter circulating miRNAs profiles that might be used as novel biomarkers to monitor acute and chronic changes due to exercise in various tissues.

  20. Vascular plant response to windthrow severity in Norwy spruce-dominated Myrtillus siie type forests in Estonia

    NARCIS (Netherlands)

    Ilisson, T.; Metslaid, M.; Vodde, F.; Jogiste, K.; Kurm, M.

    2006-01-01

    Species composition and number of species in ground vegetation after windthrow varies depending on damage severity and management actions after a storm event. In this paper we seek to determine the changes in species composition depending on the severity of storm damage. The vegetation response was

  1. Augmentation of sensory-evoked hemodynamic response in an early Alzheimer's disease mouse model.

    Science.gov (United States)

    Kim, Jinho; Jeong, Yong

    2013-01-01

    Based on enlarged blood oxygen level-dependent (BOLD) responses in cognitively normal subjects at risk for Alzheimer's disease (AD), compensatory neuronal hyperactivation has been proposed as an early marker for diagnosis of AD. The BOLD response results from neurovascular coupling, i.e., hemodynamic response induced by neuronal activity. However, there has been no evidence of task-induced increases in hemodynamic response in animal models of AD. Here, we observed an augmented hemodynamic response pattern in a transgenic AβPP(SWE)/PS1ΔE9 mouse model of AD using three in vivo imaging methods: intrinsic optical signal imaging, multi-photon laser scanning microscopy, and laser Doppler flowmetry. Sensory stimulation resulted in augmented and prolonged hemodynamic responses in transgenic mice evidenced by changes in total, oxygenated, and deoxygenated hemoglobin concentration. This difference between transgenic and wild-type mice was significant at 7 months of age when amyloid plaques and cerebral amyloid angiopathy had developed but not at younger or older ages. Correspondingly, sensory stimulation-induced pial arteriole diameter was also augmented and prolonged in transgenic mice at 7 months of age. Cerebral blood flow response in transgenic mice was augmented but not prolonged. These results are consistent with the existence of BOLD signal hyperactivation in non-demented AD-risk human subjects, supporting its potential use as an early diagnostic marker of AD.

  2. Vascular remodeling and mineralocorticoids.

    Science.gov (United States)

    Weber, K T; Sun, Y; Campbell, S E; Slight, S H; Ganjam, V K

    1995-01-01

    Circulating mineralocorticoid hormones are so named because of their important homeostatic properties that regulate salt and water balance via their action on epithelial cells. A broader range of functions in nonclassic target cellular sites has been proposed for these steroids and includes their contribution to wound healing following injury. A chronic, inappropriate (relative to intravascular volume and dietary sodium intake) elevation of these circulating hormones evokes a wound healing response in the absence of tissue injury--a wound healing response gone awry. The adverse remodeling of vascularized tissues seen in association with chronic mineralocorticoid excess is the focus of this review.

  3. Cerebro- and Cardio-vascular Responses to Energy Drink in Young Adults: Is there a Gender Effect?

    Science.gov (United States)

    Monnard, Cathríona R; Montani, Jean-Pierre; Grasser, Erik K

    2016-01-01

    Energy drinks (EDs) are suspected to induce potential adverse cardiovascular effects and have recently been shown to reduce cerebral blood flow velocity (CBFV) in young, healthy subjects. Gender differences in CBFV in response to EDs have not previously been investigated, despite the fact that women are more prone to cardiovascular disturbances such as neurocardiogenic syncope than men. Therefore, the aim of this study was to explore gender differences in cerebrovascular and cardiovascular responses to EDs. We included 45 subjects in a retrospective analysis of pooled data from two previous randomized trials carried out in our laboratory with similar protocols. Beat-to-beat blood pressure, impedance cardiography, transcranial Doppler, and end-tidal carbon dioxide (etCO2) measurements were made for at least 20 min baseline and for 80 min following the ingestion of 355 mL of a sugar-sweetened ED. Gender and time differences in cerebrovascular and cardiovascular parameters were investigated. CBFV was significantly reduced in response to ED, with the greatest reduction observed in women compared with men (-12.3 ± 0.8 vs. -9.7 ± 0.8%, P < 0.05). Analysis of variance indicated significant time (P < 0.01) and gender × time (P < 0.01) effects. The percentage change in CBFV in response to ED was independent of body weight and etCO2. No significant gender difference in major cardiovascular parameters in response to ED was observed. ED ingestion reduced CBFV over time, with a greater reduction observed in women compared with men. Our results have potential implications for women ED consumers, as well as high-risk individuals.

  4. Using physiology and behaviour to understand the responses of fish early life stages to toxicants.

    Science.gov (United States)

    Sloman, K A; McNeil, P L

    2012-12-01

    The use of early life stages of fishes (embryos and larvae) in toxicity testing has been in existence for a long time, generally utilizing endpoints such as morphological defects and mortality. Behavioural endpoints, however, may represent a more insightful evaluation of the ecological effects of toxicants. Indeed, recent years have seen a considerable increase in the use of behavioural measurements in early life stages reflecting a substantial rise in zebrafish Danio rerio early life-stage toxicity testing and the development of automated behavioural monitoring systems. Current behavioural endpoints identified for early life stages in response to toxicant exposure include spontaneous activity, predator avoidance, capture of live food, shoaling ability and interaction with other individuals. Less frequently used endpoints include measurement of anxiogenic behaviours and cognitive ability, both of which are suggested here as future indicators of toxicant disruption. For many simple behavioural endpoints, there is still a need to link behavioural effects with ecological relevance; currently, only a limited number of studies have addressed this issue. Understanding the physiological mechanisms that underlie toxicant effects on behaviour so early in life has received far less attention, perhaps because physiological measurements can be difficult to carry out on individuals of this size. The most commonly established physiological links with behavioural disruption in early life stages are similar to those seen in juveniles and adults including sensory deprivation (olfaction, lateral line and vision), altered neurogenesis and neurotransmitter concentrations. This review highlights the importance of understanding the integrated behavioural and physiological response of early life stages to toxicants and identifies knowledge gaps which present exciting areas for future research. © 2012 The Authors. Journal of Fish Biology © 2012 The Fisheries Society of the British Isles.

  5. Early and late rate of force development: differential adaptive responses to resistance training?

    DEFF Research Database (Denmark)

    Andersen, L L; Andersen, Jesper Løvind; Zebis, M K

    2010-01-01

    The objective of this study is to investigate the potentially opposing influence of qualitative and quantitative muscular adaptations in response to high-intensity resistance training on contractile rate of force development (RFD) in the early (200 ms) of rising muscle force. Fifteen healthy young......-intensity resistance training due to differential influences of qualitative and quantitative muscular adaptations on early and later phases of rising muscle force....... males participated in a 14-week resistance training intervention for the lower body and 10 matched subjects participated as controls. Maximal muscle strength (MVC) and RFD were measured during maximal voluntary isometric contraction of the quadriceps femoris muscle. Muscle biopsies were obtained from...

  6. Transcriptional regulatory network triggered by oxidative signals configures the early response mechanisms of japonica rice to chilling stress

    KAUST Repository

    Yun, Kil-Young; Park, Myoung Ryoul; Mohanty, Bijayalaxmi; Herath, Venura; Xu, Fuyu; Mauleon, Ramil; Wijaya, Edward; Bajic, Vladimir B.; Bruskiewich, Richard; de los Reyes, Benildo G

    2010-01-01

    -plant level analyses established a holistic view of chilling stress response mechanism of japonica rice. Early response regulatory network triggered by oxidative signals is critical for prolonged survival under sub-optimal temperature. Integration of stress

  7. Date syrup-derived polyphenols attenuate angiogenic responses and exhibits anti-inflammatory activity mediated by vascular endothelial growth factor and cyclooxygenase-2 expression in endothelial cells.

    Science.gov (United States)

    Taleb, Hajer; Morris, R Keith; Withycombe, Cathryn E; Maddocks, Sarah E; Kanekanian, Ara D

    2016-07-01

    Bioactive components such as polyphenols, present in many plants, are purported to have anti-inflammatory and antiangiogenic properties. Date syrup, produced from date fruit of the date palm tree, has traditionally been used to treat a wide range of diseases with etiologies involving angiogenesis and inflammation. It was hypothesized that polyphenols in date syrup reduce angiogenic responses such as cell migration, tube formation, and matrix metalloproteinase activity in an inflammatory model by exhibiting anti-inflammatory activity mediated by vascular endothelial growth factor (VEGF) and the prostaglandin enzyme cyclooxygenase-2 (COX-2) in endothelial cells. Date syrup polyphenols at 60 and 600μg/mL reduced inflammation and suppressed several stages of angiogenesis, including endothelial cell migration, invasion, matrix metalloproteinase activity, and tube formation, without evidence of cytotoxicity. VEGF and COX-2 expression induced by tumor necrosis factor-alpha at both gene expression and protein level was significantly reduced by date syrup polyphenols in comparison to untreated cells. In conclusion, polyphenols in date syrup attenuated angiogenic responses and exhibited anti-inflammatory activity mediated by VEGF and COX-2 expression in endothelial cells. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Oscillation of Angiogenesis and Vascular Dropout in Progressive Human Vascular Disease. [Vascular Pattern as Useful Read-Out of Complex Molecular Signaling

    Science.gov (United States)

    Parsons-Wingerter, Patricia

    2010-01-01

    When analyzed by VESsel GENeration Analysis (VESGEN) software, vascular patterns provide useful integrative read-outs of complex, interacting molecular signaling pathways. Using VESGEN, we recently discovered and published our innovative, surprising findings that angiogenesis oscillated with vascular dropout throughout progression of diabetic retinopathy, a blinding vascular disease. Our findings provide a potential paradigm shift in the current prevailing view on progression and treatment of this disease, and a new early-stage window of regenerative therapeutic opportunities. The findings also suggest that angiogenesis may oscillate with vascular disease in a homeostatic-like manner during early stages of other inflammatory progressive diseases such as cancer and coronary vascular disease.

  9. Polyisocyanopeptide hydrogels: A novel thermo-responsive hydrogel supporting pre-vascularization and the development of organotypic structures.

    Science.gov (United States)

    Zimoch, Jakub; Padial, Joan Simó; Klar, Agnes S; Vallmajo-Martin, Queralt; Meuli, Martin; Biedermann, Thomas; Wilson, Christopher J; Rowan, Alan; Reichmann, Ernst

    2018-04-01

    Molecular and mechanical interactions with the 3D extracellular matrix are essential for cell functions such as survival, proliferation, migration, and differentiation. Thermo-responsive biomimetic polyisocyanopeptide (PIC) hydrogels are promising new candidates for 3D cell, tissue, and organ cultures. This is a synthetic, thermo-responsive and stress-stiffening material synthesized via polymerization of the corresponding monomers using a nickel perchlorate as a catalyst. It can be tailored to meet various demands of cells by modulating its stiffness and through the decoration of the polymer with short GRGDS peptides using copper free click chemistry. These peptides make the hydrogels biocompatible by mimicking the binding sites of certain integrins. This study focuses on the optimization of the PIC polymer properties for efficient cell, tissue and organ development. Screening for the optimal stiffness of the hydrogel and the ideal concentration of the GRGDS ligand conjugated with the polymer, enabled cell proliferation, migration and differentiation of various primary cell types of human origin. We demonstrate that fibroblasts, endothelial cells, adipose-derived stem cells and melanoma cells, do survive, thrive and differentiate in optimized PIC hydrogels. Importantly, these hydrogels support the spontaneous formation of complex structures like blood capillaries in vitro. Additionally, we utilized the thermo-responsive properties of the hydrogels for a rapid and gentle recovery of viable cells. Finally, we show that organotypic structures of human origin grown in PIC hydrogels can be successfully transplanted subcutaneously onto immune-compromised rats, on which they survive and integrate into the surrounding tissue. Molecular and mechanical interactions with the surrounding environment are essential for cell functions. Although 2D culture systems greatly contributed to our understanding of complex biological phenomena, they cannot substitute for crucial

  10. Girls’ challenging social experiences in early adolescence predict neural response to rewards and depressive symptoms

    Directory of Open Access Journals (Sweden)

    Melynda D. Casement

    2014-04-01

    Full Text Available Developmental models of psychopathology posit that exposure to social stressors may confer risk for depression in adolescent girls by disrupting neural reward circuitry. The current study tested this hypothesis by examining the relationship between early adolescent social stressors and later neural reward processing and depressive symptoms. Participants were 120 girls from an ongoing longitudinal study of precursors to depression across adolescent development. Low parental warmth, peer victimization, and depressive symptoms were assessed when the girls were 11 and 12 years old, and participants completed a monetary reward guessing fMRI task and assessment of depressive symptoms at age 16. Results indicate that low parental warmth was associated with increased response to potential rewards in the medial prefrontal cortex (mPFC, striatum, and amygdala, whereas peer victimization was associated with decreased response to potential rewards in the mPFC. Furthermore, concurrent depressive symptoms were associated with increased reward anticipation response in mPFC and striatal regions that were also associated with early adolescent psychosocial stressors, with mPFC and striatal response mediating the association between social stressors and depressive symptoms. These findings are consistent with developmental models that emphasize the adverse impact of early psychosocial stressors on neural reward processing and risk for depression in adolescence.

  11. Artificial Neural Network-Based Early-Age Concrete Strength Monitoring Using Dynamic Response Signals.

    Science.gov (United States)

    Kim, Junkyeong; Lee, Chaggil; Park, Seunghee

    2017-06-07

    Concrete is one of the most common materials used to construct a variety of civil infrastructures. However, since concrete might be susceptible to brittle fracture, it is essential to confirm the strength of concrete at the early-age stage of the curing process to prevent unexpected collapse. To address this issue, this study proposes a novel method to estimate the early-age strength of concrete, by integrating an artificial neural network algorithm with a dynamic response measurement of the concrete material. The dynamic response signals of the concrete, including both electromechanical impedances and guided ultrasonic waves, are obtained from an embedded piezoelectric sensor module. The cross-correlation coefficient of the electromechanical impedance signals and the amplitude of the guided ultrasonic wave signals are selected to quantify the variation in dynamic responses according to the strength of the concrete. Furthermore, an artificial neural network algorithm is used to verify a relationship between the variation in dynamic response signals and concrete strength. The results of an experimental study confirm that the proposed approach can be effectively applied to estimate the strength of concrete material from the early-age stage of the curing process.

  12. Natural killer cells promote early CD8 T cell responses against cytomegalovirus.

    Directory of Open Access Journals (Sweden)

    Scott H Robbins

    2007-08-01

    Full Text Available Understanding the mechanisms that help promote protective immune responses to pathogens is a major challenge in biomedical research and an important goal for the design of innovative therapeutic or vaccination strategies. While natural killer (NK cells can directly contribute to the control of viral replication, whether, and how, they may help orchestrate global antiviral defense is largely unknown. To address this question, we took advantage of the well-defined molecular interactions involved in the recognition of mouse cytomegalovirus (MCMV by NK cells. By using congenic or mutant mice and wild-type versus genetically engineered viruses, we examined the consequences on antiviral CD8 T cell responses of specific defects in the ability of the NK cells to control MCMV. This system allowed us to demonstrate, to our knowledge for the first time, that NK cells accelerate CD8 T cell responses against a viral infection in vivo. Moreover, we identify the underlying mechanism as the ability of NK cells to limit IFN-alpha/beta production to levels not immunosuppressive to the host. This is achieved through the early control of cytomegalovirus, which dramatically reduces the activation of plasmacytoid dendritic cells (pDCs for cytokine production, preserves the conventional dendritic cell (cDC compartment, and accelerates antiviral CD8 T cell responses. Conversely, exogenous IFN-alpha administration in resistant animals ablates cDCs and delays CD8 T cell activation in the face of NK cell control of viral replication. Collectively, our data demonstrate that the ability of NK cells to respond very early to cytomegalovirus infection critically contributes to balance the intensity of other innate immune responses, which dampens early immunopathology and promotes optimal initiation of antiviral CD8 T cell responses. Thus, the extent to which NK cell responses benefit the host goes beyond their direct antiviral effects and extends to the prevention of innate

  13. Early Peritoneal Immune Response during Echinococcus granulosus Establishment Displays a Biphasic Behavior

    Science.gov (United States)

    Mourglia-Ettlin, Gustavo; Marqués, Juan Martín; Chabalgoity, José Alejandro; Dematteis, Sylvia

    2011-01-01

    Background Cystic echinococcosis is a worldwide distributed helminth zoonosis caused by the larval stage of Echinococcus granulosus. Human secondary cystic echinococcosis is caused by dissemination of protoscoleces after accidental rupture of fertile cysts and is due to protoscoleces ability to develop into new metacestodes. In the experimental model of secondary cystic echinococcosis mice react against protoscoleces producing inefficient immune responses, allowing parasites to develop into cysts. Although the chronic phase of infection has been analyzed in depth, early immune responses at the site of infection establishment, e.g., peritoneal cavity, have not been well studied. Because during early stages of infection parasites are thought to be more susceptible to immune attack, this work focused on the study of cellular and molecular events triggered early in the peritoneal cavity of infected mice. Principal Findings Data obtained showed disparate behaviors among subpopulations within the peritoneal lymphoid compartment. Regarding B cells, there is an active molecular process of plasma cell differentiation accompanied by significant local production of specific IgM and IgG2b antibodies. In addition, peritoneal NK cells showed a rapid increase with a significant percentage of activated cells. Peritoneal T cells showed a substantial increase, with predominance in CD4+ T lymphocytes. There was also a local increase in Treg cells. Finally, cytokine response showed local biphasic kinetics: an early predominant induction of Th1-type cytokines (IFN-γ, IL-2 and IL-15), followed by a shift toward a Th2-type profile (IL-4, IL-5, IL-6, IL-10 and IL-13). Conclusions Results reported here open new ways to investigate the involvement of immune effectors players in E. granulosus establishment, and also in the sequential promotion of Th1- toward Th2-type responses in experimental secondary cystic echinococcosis. These data would be relevant for designing rational therapies

  14. Early warning systems and rapid response to the deteriorating patient in hospital: A realist evaluation.

    Science.gov (United States)

    McGaughey, Jennifer; O'Halloran, Peter; Porter, Sam; Trinder, John; Blackwood, Bronagh

    2017-12-01

    To test the Rapid Response Systems programme theory against actual practice components of the Rapid Response Systems implemented to identify those contexts and mechanisms which have an impact on the successful achievement of desired outcomes in practice. Rapid Response Systems allow deteriorating patients to be recognized using Early Warning Systems, referred early via escalation protocols and managed at the bedside by competent staff. Realist evaluation. The research design was an embedded multiple case study approach of four wards in two hospitals in Northern Ireland which followed the principles of Realist Evaluation. We used various mixed methods including individual and focus group interviews, observation of nursing practice between June-November 2010 and document analysis of Early Warning Systems audit data between May-October 2010 and hospital acute care training records over 4.5 years from 2003-2008. Data were analysed using NiVivo8 and SPPS. A cross-case analysis highlighted similar patterns of factors which enabled or constrained successful recognition, referral and response to deteriorating patients in practice. Key enabling factors were the use of clinical judgement by experienced nurses and the empowerment of nurses as a result of organizational change associated with implementation of Early Warning System protocols. Key constraining factors were low staffing and inappropriate skill mix levels, rigid implementation of protocols and culturally embedded suboptimal communication processes. Successful implementation of Rapid Response Systems was dependent on adopting organizational and cultural changes that facilitated staff empowerment, flexible implementation of protocols and ongoing experiential learning. © 2017 John Wiley & Sons Ltd.

  15. The Impact of Early Substance Use Disorder Treatment Response on Treatment Outcomes Among Pregnant Women With Primary Opioid Use.

    Science.gov (United States)

    Tuten, Michelle; Fitzsimons, Heather; Hochheimer, Martin; Jones, Hendree E; Chisolm, Margaret S

    2018-03-13

    This study examined the impact of early patient response on treatment utilization and substance use among pregnant participants enrolled in substance use disorder (SUD) treatment. Treatment responders (TRs) and treatment nonresponders (TNRs) were compared on pretreatment and treatment measures. Regression models predicted treatment utilization and substance use. TR participants attended more treatment and had lower rates of substance use relative to TNR participants. Regression models for treatment utilization and substance use were significant. Maternal estimated gestational age (EGA) and baseline cocaine use were negatively associated with treatment attendance. Medication-assisted treatment, early treatment response, and baseline SUD treatment were positively associated with treatment attendance. Maternal EGA was negatively associated with counseling attendance; early treatment response was positively associated with counseling attendance. Predictors of any substance use at 1 month were maternal education, EGA, early treatment nonresponse, and baseline cocaine use. The single predictor of any substance use at 2 months was early treatment nonresponse. Predictors of opioid use at 1 month were maternal education, EGA, early treatment nonresponse, and baseline SUD treatment. Predictors of opioid use at 2 months were early treatment nonresponse, and baseline cocaine and marijuana use. Predictors of cocaine use at 1 month were early treatment nonresponse, baseline cocaine use, and baseline SUD treatment. Predictors of cocaine use at 2 months were early treatment nonresponse and baseline cocaine use. Early treatment response predicts more favorable maternal treatment utilization and substance use outcomes. Treatment providers should implement interventions to maximize patient early response to treatment.

  16. Prediction of Early Response to Chemotherapy in Lung Cancer by Using Diffusion-Weighted MR Imaging

    Directory of Open Access Journals (Sweden)

    Jing Yu

    2014-01-01

    Full Text Available Purpose. To determine whether change of apparent diffusion coefficient (ADC value could predict early response to chemotherapy in lung cancer. Materials and Methods. Twenty-five patients with advanced non-small cell lung cancer underwent chest MR imaging including DWI before and at the end of the first cycle of chemotherapy. The tumor’s mean ADC value and diameters on MR images were calculated and compared. The grouping reference was based on serial CT scans according to Response Evaluation Criteria in Solid Tumors. Logistic regression was applied to assess treatment response prediction ability of ADC value and diameters. Results. The change of ADC value in partial response group was higher than that in stable disease group (P=0.004. ROC curve showed that ADC value could predict treatment response with 100% sensitivity, 64.71% specificity, 57.14% positive predictive value, 100% negative predictive value, and 82.7% accuracy. The area under the curve for combination of ADC value and longest diameter change was higher than any parameter alone (P≤0.01. Conclusions. The change of ADC value may be a sensitive indicator to predict early response to chemotherapy in lung cancer. Prediction ability could be improved by combining the change of ADC value and longest diameter.

  17. Early experience with X-ray magnetic resonance fusion for low-flow vascular malformations in the pediatric interventional radiology suite

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Tiffany J. [The Children' s Hospital of Philadelphia, Department of Radiology, Philadelphia, PA (United States); Keck School of Medicine of the University of Southern California, Los Angeles, CA (United States); Girard, Erin [Siemens Corporation, Corporate Technology, Princeton, NJ (United States); Shellikeri, Sphoorti; Vossough, Arastoo; Ho-Fung, Victor; Cahill, Anne Marie [The Children' s Hospital of Philadelphia, Department of Radiology, Philadelphia, PA (United States); Setser, Randolph [Siemens Medical Solutions USA, Inc., Hoffman Estates, IL (United States)

    2016-03-15

    This technical innovation describes our experience using an X-ray magnetic resonance fusion (XMRF) software program to overlay 3-D MR images on real-time fluoroscopic images during sclerotherapy procedures for vascular malformations at a large pediatric institution. Five cases have been selected to illustrate the application and various clinical utilities of XMRF during sclerotherapy procedures as well as the technical limitations of this technique. The cases demonstrate how to use XMRF in the interventional suite to derive additional information to improve therapeutic confidence with regards to the extent of lesion filling and to guide clinical management in terms of intraprocedural interventional measures. (orig.)

  18. Early diagnosis of congenital vascular malformation as a condition to rapid prevention of complications – case study

    OpenAIRE

    Dominika Jaguś; Agata Rutkowska; Paweł Wareluk

    2017-01-01

    Klippel–Trénaunay syndrome is a rare congenital condition characterised by a triad of symptoms: capillary-lymphatic-venous malformations, varicose veins and venous malformations as well as soft tissue and skeletal hypertrophy of the affected limb. In this article, we present a case of a 5-year-old boy with extensive vascular malformations of the lower limbs and the buttock region. In this case, manifestation of all three symptoms was gradual. At the age of 4 years, the patient was ad...

  19. Discrimination of bilateral finger photoplethysmogram responses to reactive hyperemia in diabetic and healthy subjects using a differential vascular model framework

    International Nuclear Information System (INIS)

    Keikhosravi, Adib; Aghajani, Haleh; Zahedi, Edmond

    2013-01-01

    Endothelial dysfunction assessment has received considerable attention due to its potential in early screening of cardiovascular diseases. Since the seminal work by Celermajer in flow-mediated dilation (FMD) based on B-mode ultrasound measurement of the brachial artery dilation following limb ischemia, many attempts have been made toward applying this method to clinical, non-invasive endothelial dysfunction assessment. One major obstacle toward achieving this objective has been the relative high cost of the required setup and skilled manpower. Such limitations have prompted the investigation of other non-invasively accessible signals such as the photoplethysmogram (PPG) in relation to FMD. It is in the above context that this paper proposes to use a modified version of an existing differential model of the human upper vasculature in order to discriminate between healthy and diabetic subjects. PPG from 46 subjects (23 healthy and 23 diabetic) were utilized to identify the model parameters. Once the model parameters were identified, singular value decomposition was applied to reduce the number of features and increase the separability. Finally, a naive Bayes classifier resulted in an overall accuracy of 93.5% (Spec. 87.0% and Sens. 100%). Taking into account subjects’ gender further improved the overall accuracy. It is thought that the application of the proposed method to endothelial dysfunction assessment may positively impact the deployment of FMD in clinical settings. (paper)

  20. The wavelet transform as a tool for the characterization of the vascular response in the human lower limb

    Directory of Open Access Journals (Sweden)

    Henrique Silva

    2014-06-01

    Full Text Available In recent years, cutaneous microcirculation gained considerable interest for the assessment of microcirculation function and dysfunction mechanisms. Laser Doppler Flowmetry (LDF is a noninvasive and widely employed technology to study microcirculation. It provides a complex signal that may be decomposed by wavelet analysis into several components at characteristic frequency ranges. These are related to the heart (0.6 Hz to 2 Hz, respiration (0.15 Hz to 0.6 Hz, myogenic activity in the vessel wall (0.052 Hz to 0.15 Hz, sympathetic activity (0.021 Hz to 0.052 Hz and endothelial (nitric oxide-mediated activity (0.0095 Hz to 0.021 Hz. A group of 30 healthy (22.3 ± 3.1 years old subjects , giving previously informed consent, tested two perfusion-restricting protocols which allowed us to study the circulatory response in the lower limb: (1 passive leg elevation from the supine position for 10 minutes, (2 inflated cuff occlusion at the ankle level for 3 minutes from the sitting position. The LDF signal was partitioned using a Morlet wavelet model. Data analysis revealed significantly lower components’ amplitudes for both protocols during provocation, with consistently lower values for protocol 1 in relation to protocol 2. Significant gender differences were found for protocol 1 but not for protocol 2. These results demonstrate the usefulness of the wavelet analysis to assess each LDF signal component as part of the physiological response to the lower limb microcirculation regulation.

  1. Multimodality multiparametric imaging of early tumor response to a novel antiangiogenic therapy based on anticalins.

    Directory of Open Access Journals (Sweden)

    Reinhard Meier

    Full Text Available Anticalins are a novel class of targeted protein therapeutics. The PEGylated Anticalin Angiocal (PRS-050-PEG40 is directed against VEGF-A. The purpose of our study was to compare the performance of diffusion weighted imaging (DWI, dynamic contrast enhanced magnetic resonance imaging (DCE-MRI and positron emission tomography with the tracer [18F]fluorodeoxyglucose (FDG-PET for monitoring early response to antiangiogenic therapy with PRS-050-PEG40. 31 mice were implanted subcutaneously with A673 rhabdomyosarcoma xenografts and underwent DWI, DCE-MRI and FDG-PET before and 2 days after i.p. injection of PRS-050-PEG40 (n = 13, Avastin (n = 6 or PBS (n = 12. Tumor size was measured manually with a caliper. Imaging results were correlated with histopathology. In the results, the tumor size was not significantly different in the treatment groups when compared to the control group on day 2 after therapy onset (P = 0.09. In contrast the imaging modalities DWI, DCE-MRI and FDG-PET showed significant differences between the therapeutic compared to the control group as early as 2 days after therapy onset (P<0.001. There was a strong correlation of the early changes in DWI, DCE-MRI and FDG-PET at day 2 after therapy onset and the change in tumor size at the end of therapy (r = -0.58, 0.71 and 0.67 respectively. The imaging results were confirmed by histopathology, showing early necrosis and necroptosis in the tumors. Thus multimodality multiparametric imaging was able to predict therapeutic success of PRS-050-PEG40 and Avastin as early as 2 days after onset of therapy and thus promising for monitoring early response of antiangiogenic therapy.

  2. Reduced butyrylcholinesterase activity is an early indicator of trauma-induced acute systemic inflammatory response

    Directory of Open Access Journals (Sweden)

    Zivkovic AR

    2016-11-01

    Full Text Available Aleksandar R Zivkovic, Jochen Bender, Thorsten Brenner, Stefan Hofer,* Karsten Schmidt* Department of Anesthesiology, Heidelberg University Hospital, Heidelberg, Germany *These authors contributed equally to this work Purpose: Early diagnosis of systemic inflammatory response syndrome is fundamentally important for an effective and a goal-directed therapy. Various inflammation biomarkers have been used in clinical and experimental practice. However, a definitive diagnostic tool for an early detection of systemic inflammation remains to be identified. Acetylcholine (Ach has been shown to play an important role in the inflammatory response. Serum cholinesterase (butyrylcholinesterase [BChE] is the major Ach hydrolyzing enzyme in blood. The role of this enzyme during inflammation has not yet been fully understood. This study tests whether a reduction in the BChE activity could indicate the onset of the systemic inflammatory response upon traumatic injury. Patients and methods: This observational study measured BChE activity in patients with traumatic injury admitted to the emergency room by using point-of-care-test system (POCT. In addition, the levels of routine inflammation biomarkers during the initial treatment period were measured. Injury Severity Score was used to assess the trauma severity. Results: Altered BChE activity was correlated with trauma severity, resulting in systemic inflammation. Reduction in the BChE activity was detected significantly earlier compared to those of routinely measured inflammatory biomarkers. Conclusion: This study suggests that the BChE activity reduction might serve as an early indicator of acute systemic inflammation. Furthermore, BChE activity, measured using a POCT system, might play an important role in the early diagnosis of the trauma-induced systemic inflammation. Keywords: trauma, injury, early diagnostics, cholinergic, pseudocholinesterase, SIRS

  3. Cortisol Stress Response Variability in Early Adolescence Attachment, Affect and Sex

    Science.gov (United States)

    Cameron, Catherine Ann; McKay, Stacey; Susman, Elizabeth J.; Wynne-Edwards, Katherine; Wright, Joan M.; Weinberg, Joanne

    2017-01-01

    Attachment, affect, and sex shape responsivity to psychosocial stress. Concurrent social contexts influence cortisol secretion, a stress hormone and biological marker of hypothalamic–pituitary–adrenal axis activity. Patterns of attachment, emotion status, and sex were hypothesized to relate to bifurcated, that is, accentuated and attenuated, cortisol reactivity. The theoretical framework for this study posits that multiple individual differences mediate a cortisol stress response. The effects of two psychosocial stress interventions, a modified Trier Social Stress Test for Teens and the Frustration Social Stressor for Adolescents were developed and investigated with early adolescents. Both of these protocols induced a significant stress reaction and evoked predicted bifurcation in cortisol responses; an increase or decrease from baseline to reactivity. In Study I, 120 predominantly middle-class, Euro-Canadian early adolescents with a mean age of 13.43 years were studied. The girls' attenuated cortisol reactivity to the public performance stressor related significantly to their self-reported lower maternal-attachment and higher trait-anger. In Study II, a community sample of 146 predominantly Euro-Canadian middle-class youth, with an average age of 14.5 years participated. Their self-reports of higher trait-anger and trait-anxiety, and lower parental attachment by both sexes related differentially to accentuated and attenuated cortisol reactivity to the frustration stressor. Thus, attachment, affect, sex, and the stressor contextual factors were associated with the adrenal-cortical responses of these adolescents through complex interactions. Further studies of individual differences in physiological responses to stress are called for in order to clarify the identities of concurrent protective and risk factors in the psychosocial stress and physiological stress responses of early adolescents. PMID:27468997

  4. Cortisol Stress Response Variability in Early Adolescence: Attachment, Affect and Sex.

    Science.gov (United States)

    Cameron, Catherine Ann; McKay, Stacey; Susman, Elizabeth J; Wynne-Edwards, Katherine; Wright, Joan M; Weinberg, Joanne

    2017-01-01

    Attachment, affect, and sex shape responsivity to psychosocial stress. Concurrent social contexts influence cortisol secretion, a stress hormone and biological marker of hypothalamic-pituitary-adrenal axis activity. Patterns of attachment, emotion status, and sex were hypothesized to relate to bifurcated, that is, accentuated and attenuated, cortisol reactivity. The theoretical framework for this study posits that multiple individual differences mediate a cortisol stress response. The effects of two psychosocial stress interventions, a modified Trier Social Stress Test for Teens and the Frustration Social Stressor for Adolescents were developed and investigated with early adolescents. Both of these protocols induced a significant stress reaction and evoked predicted bifurcation in cortisol responses; an increase or decrease from baseline to reactivity. In Study I, 120 predominantly middle-class, Euro-Canadian early adolescents with a mean age of 13.43 years were studied. The girls' attenuated cortisol reactivity to the public performance stressor related significantly to their self-reported lower maternal-attachment and higher trait-anger. In Study II, a community sample of 146 predominantly Euro-Canadian middle-class youth, with an average age of 14.5 years participated. Their self-reports of higher trait-anger and trait-anxiety, and lower parental attachment by both sexes related differentially to accentuated and attenuated cortisol reactivity to the frustration stressor. Thus, attachment, affect, sex, and the stressor contextual factors were associated with the adrenal-cortical responses of these adolescents through complex interactions. Further studies of individual differences in physiological responses to stress are called for in order to clarify the identities of concurrent protective and risk factors in the psychosocial stress and physiological stress responses of early adolescents.

  5. Activity-Dependent Calcium, Oxygen, and Vascular Responses in a Mouse Model of Familial Hemiplegic Migraine Type 1

    DEFF Research Database (Denmark)

    Khennouf, Lila; Gesslein, Bodil; Lind, Barbara Lykke

    2016-01-01

    it with assessment of local field potentials by electrophysiological recordings, cerebral blood flow by laser Doppler flowmetry, and oxygen consumption with measurement of the oxygen tissue tension. Results: During spreading depression, the evoked increase in cytosolic Ca2+ was larger and faster in FHM1 mice than...... wild-type (WT) mice. It was accompanied by larger increases in oxygen consumption in FHM1 mice, leading to tissue anoxia, but moderate hypoxia, in WT mice. In comparison, before CSD, Ca2+ and hemodynamic responses to somatosensory stimulations were smaller in FHM1 mice than WT mice and almost abolished...... after CSD. The CSD-induced Ca2+ changes were mitigated by the CaV2.1 gating modifier, tert-butyl dihydroquinone. Interpretation: Our findings suggest that tissue anoxia might be a mechanism for prolonged aura in FHM1. Reduced Ca2+ signals during normal network activity in FHM1 as compared to WT mice may...

  6. Vascular response to ischemia in the feet of falanga torture victims and normal controls--color and spectral Doppler findings

    DEFF Research Database (Denmark)

    Torp-Pedersen, Søren; Amris, Kirstine; Holm, Christian Cato

    2009-01-01

    to controls. On color Doppler this would be seen as less color after ischemia and on spectral Doppler as elevated resistive index (RI). METHODS: Ten male torture victims from the Middle East and nine age, sex and ethnically matched controls underwent Doppler examination of the abductor hallucis and flexor...... digitorum brevis muscles before and after two minutes ischemia induced with a pressure cuff over the malleoli. The color Doppler findings were quantified with the color fraction (CF) before and after ischemia. On spectral Doppler the resistive index was measured once before and three consecutive times after....... However, the trend in RI still supports the hypothesis. The negative findings may be due to inadequate design where the CF and RI were measured in one setting, perhaps resulting in both methods being applied imperfectly. The response to ischemia seems short-lived and we suggest that the Doppler methods...

  7. Perceived early-life maternal care and the cortisol response to repeated psychosocial stress.

    Science.gov (United States)

    Engert, Veronika; Efanov, Simona I; Dedovic, Katarina; Duchesne, Annie; Dagher, Alain; Pruessner, Jens C

    2010-11-01

    In the past decade, a body of animal and human research has revealed a profound influence of early-life experiences, ranging from variations in parenting behaviour to severe adversity, on hypothalamic-pituitary-adrenal axis regulation in adulthood. In our own previous studies, we have shown how variations in early-life parental care influence the development of the hippocampus and modify the cortisol awakening response. In the present study, we investigated the influence of early-life maternal care on cortisol, heart rate and subjective psychological responses to the repeated administration of a psychosocial laboratory stressor in a population of 63 healthy young adults. Low, medium and high early-life maternal care groups were identified using the Parental Bonding Instrument. Controlling for the effect of sex, we found an inverted u-shaped relation between increasing levels of maternal care and cortisol stress responsivity. Specifically, overall and stress-induced cortisol levels went from below normal in the low maternal care, to normal in the medium care, back to below normal in the high maternal care groups. We found no group differences with respect to heart rate and subjective psychological stress measures. Whereas low and high maternal care groups exhibited similarly low endocrine stress responses, their psychological profiles were opposed with increased levels of depression and anxiety and decreased self-esteem in the low care group. Sex was unequally distributed among maternal care groups, whereby the number of men with low maternal care was too small to allow introducing sex as a second between-group variable. We discuss the potential significance of this dissociation between endocrine and psychological parameters with respect to stress vulnerability and resistance for each maternal care group.

  8. Clinical features and early treatment response of central nervous system involvement in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Levinsen, Mette; Taskinen, Mervi; Abrahamsson, Jonas

    2014-01-01

    BACKGROUND: Central nervous system (CNS) involvement in childhood acute lymphoblastic leukemia (ALL) remains a therapeutic challenge. PROCEDURE: To explore leukemia characteristics of patients with CNS involvement at ALL diagnosis, we analyzed clinical features and early treatment response of 744...... leukemia and patients without such characteristics (0.50 vs. 0.61; P = 0.2). CONCLUSION: CNS involvement at diagnosis is associated with adverse prognostic features but does not indicate a less chemosensitive leukemia....

  9. Taking responsibility for the early assessment and treatment of patients with musculoskeletal pain

    DEFF Research Database (Denmark)

    Foster, Nadine E; Hartvigsen, Jan; Croft, Peter R

    2012-01-01

    ABSTRACT: Musculoskeletal pain is common across all populations and costly in terms of impact on the individual and, more generally, on society. In most health-care systems, the first person to see the patient with a musculoskeletal problem such as back pain is the general practitioner, and acces......, and underpinning evidence, for reconsidering who should take responsibility for the early assessment and treatment of patients with musculoskeletal problems....

  10. Strengthening Laboratory Capacity for Early Warning Alert and Response System (EWARS) in Indonesia

    OpenAIRE

    Kandel, Nirmal; Hapsari, Ratna Budi; Riana, Dyah Armi; Setiawaty, Vivi; Larasati, Wita; Wulandari, Endang; Purwanto, Edy

    2017-01-01

    Background: Establishment of Early Warning Alert and Response System (EWARS) in Indonesia was initiated since 2009 in few selected provinces and government was planning to roll out in other provinces. Before initiating this roll out the assessment of performance of EWARS in 2012 was conducted. The aim of the assessment is to strengthen laboratory for supporting to EWARS for alerts testing. Methods: Laboratory capacity mapping tool and laboratory algorithm for twenty two priority diseases of ...

  11. Early Life Arsenic Exposure and Acute and Long-term Responses to Influenza A Infection in Mice

    OpenAIRE

    Ramsey, Kathryn A.; Foong, Rachel E.; Sly, Peter D.; Larcombe, Alexander N.; Zosky, Graeme R.

    2013-01-01

    Background: Arsenic is a significant global environmental health problem. Exposure to arsenic in early life has been shown to increase the rate of respiratory infections during infancy, reduce childhood lung function, and increase the rates of bronchiectasis in early adulthood. Objective: We aimed to determine if early life exposure to arsenic exacerbates the response to early life influenza infection in mice. Methods: C57BL/6 mice were exposed to arsenic in utero and throughout postnatal lif...

  12. SPOC1-mediated antiviral host cell response is antagonized early in human adenovirus type 5 infection

    DEFF Research Database (Denmark)

    Schreiner, Sabrina; Kinkley, Sarah; Bürck, Carolin

    2013-01-01

    , and playing a role in DNA damage response. SPOC1 co-localized with viral replication centers in the host cell nucleus, interacted with Ad DNA, and repressed viral gene expression at the transcriptional level. We discovered that this SPOC1-mediated restriction imposed upon Ad growth is relieved by its...... viruses (HSV-1, HSV-2, HIV-1, and HCV) also depleted SPOC1 in infected cells. Our findings provide a general model for how pathogenic human viruses antagonize intrinsic SPOC1-mediated antiviral responses in their host cells. A better understanding of viral entry and early restrictive functions in host...

  13. Proteomic identification of early salicylate- and flg22-responsive redox-sensitive proteins in Arabidopsis

    KAUST Repository

    Liu, Peng

    2015-02-27

    Accumulation of reactive oxygen species (ROS) is one of the early defense responses against pathogen infection in plants. The mechanism about the initial and direct regulation of the defense signaling pathway by ROS remains elusive. Perturbation of cellular redox homeostasis by ROS is believed to alter functions of redox-sensitive proteins through their oxidative modifications. Here we report an OxiTRAQ-based proteomic study in identifying proteins whose cysteines underwent oxidative modifications in Arabidopsis cells during the early response to salicylate or flg22, two defense pathway elicitors that are known to disturb cellular redox homeostasis. Among the salicylate- and/or flg22-responsive redox-sensitive proteins are those involved in transcriptional regulation, chromatin remodeling, RNA processing, post-translational modifications, and nucleocytoplasmic shuttling. The identification of the salicylate-/flg22-responsive redox-sensitive proteins provides a foundation from which further study can be conducted toward understanding biological significance of their oxidative modifications during the plant defense response.

  14. Postoperative radiographic evaluation of vascularized fibular grafts

    International Nuclear Information System (INIS)

    Manaster, B.J.; Coleman, D.A.; Bell, D.A.

    1989-01-01

    This paper reports on thirty-five patients with free vascularized fibular grafts examined postoperatively with plain radiography. Early graft incorporation is seen as a fuzziness of the cortex at the site of its insertion into the host bone. Causes of failure in grafting for bone defects include graft fracture, hardware failure, and infection. A high percentage of complications or at least delayed unions occurred when vascularized fibular grafts were used to fill defects in the lower extremity. Conversely, upper extremity defects bridged by vascularized grafts heal quickly and hypertrophy. Vascularized grafts placed in the femoral head and neck for a vascular necrosis incorporate early on their superior aspect. The osseous tunnel in which they are placed is normally wider than the graft and often becomes sclerotic; this appearance does not represent nonunion

  15. Cellular dysfunction in the diabetic fibroblast: impairment in migration, vascular endothelial growth factor production, and response to hypoxia.

    Science.gov (United States)

    Lerman, Oren Z; Galiano, Robert D; Armour, Mary; Levine, Jamie P; Gurtner, Geoffrey C

    2003-01-01

    Although it is known that systemic diseases such as diabetes result in impaired wound healing, the mechanism for this impairment is not understood. Because fibroblasts are essential for wound repair, we compared the in vitro behavior of fibroblasts cultured from diabetic, leptin receptor-deficient (db/db) mice with wild-type fibroblasts from mice of the same genetic background in processes important during tissue repair. Adult diabetic mouse fibroblast migration exhibited a 75% reduction in migration compared to normal fibroblasts (P under basal or hypoxic conditions, confirming that the results from db/db fibroblasts in mature mice resulted from the diabetic state and were not because of alterations in the leptin-leptin receptor axis. Markers of cellular viability including proliferation and senescence were not significantly different between diabetic and wild-type fibroblasts. We conclude that, in vitro, diabetic fibroblasts show selective impairments in discrete cellular processes critical for tissue repair including cellular migration, VEGF production, and the response to hypoxia. The VEGF abnormalities developed concurrently with the onset of hyperglycemia and were not seen in normoglycemic, leptin receptor-deficient db/db mice. These observations support a role for fibroblast dysfunction in the impaired wound healing observed in human diabetics, and also suggest a mechanism for the poor clinical outcomes that occur after ischemic injury in diabetic patients.

  16. Expression of putative immune response genes during early ontogeny in the coral Acropora millepora.

    Directory of Open Access Journals (Sweden)

    Eneour Puill-Stephan

    Full Text Available Corals, like many other marine invertebrates, lack a mature allorecognition system in early life history stages. Indeed, in early ontogeny, when corals acquire and establish associations with various surface microbiota and dinoflagellate endosymbionts, they do not efficiently distinguish between closely and distantly related individuals from the same population. However, very little is known about the molecular components that underpin allorecognition and immunity responses or how they change through early ontogeny in corals.Patterns in the expression of four putative immune response genes (apextrin, complement C3, and two CELIII type lectin genes were examined in juvenile colonies of Acropora millepora throughout a six-month post-settlement period using quantitative real-time PCR (qPCR. Expression of a CELIII type lectin gene peaked in the fourth month for most of the coral juveniles sampled and was significantly higher at this time than at any other sampling time during the six months following settlement. The timing of this increase in expression levels of putative immune response genes may be linked to allorecognition maturation which occurs around this time in A. millepora. Alternatively, the increase may represent a response to immune challenges, such as would be involved in the recognition of symbionts (such as Symbiodinium spp. or bacteria during winnowing processes as symbioses are fine-tuned.Our data, although preliminary, are consistent with the hypothesis that lectins may play an important role in the maturation of allorecognition responses in corals. The co-expression of lectins with apextrin during development of coral juveniles also raises the possibility that these proteins, which are components of innate immunity in other invertebrates, may influence the innate immune systems of corals through a common pathway or system. However, further studies investigating the expression of these genes in alloimmune-challenged corals are

  17. Expression of putative immune response genes during early ontogeny in the coral Acropora millepora.

    Science.gov (United States)

    Puill-Stephan, Eneour; Seneca, François O; Miller, David J; van Oppen, Madeleine J H; Willis, Bette L

    2012-01-01

    Corals, like many other marine invertebrates, lack a mature allorecognition system in early life history stages. Indeed, in early ontogeny, when corals acquire and establish associations with various surface microbiota and dinoflagellate endosymbionts, they do not efficiently distinguish between closely and distantly related individuals from the same population. However, very little is known about the molecular components that underpin allorecognition and immunity responses or how they change through early ontogeny in corals. Patterns in the expression of four putative immune response genes (apextrin, complement C3, and two CELIII type lectin genes) were examined in juvenile colonies of Acropora millepora throughout a six-month post-settlement period using quantitative real-time PCR (qPCR). Expression of a CELIII type lectin gene peaked in the fourth month for most of the coral juveniles sampled and was significantly higher at this time than at any other sampling time during the six months following settlement. The timing of this increase in expression levels of putative immune response genes may be linked to allorecognition maturation which occurs around this time in A. millepora. Alternatively, the increase may represent a response to immune challenges, such as would be involved in the recognition of symbionts (such as Symbiodinium spp. or bacteria) during winnowing processes as symbioses are fine-tuned. Our data, although preliminary, are consistent with the hypothesis that lectins may play an important role in the maturation of allorecognition responses in corals. The co-expression of lectins with apextrin during development of coral juveniles also raises the possibility that these proteins, which are components of innate immunity in other invertebrates, may influence the innate immune systems of corals through a common pathway or system. However, further studies investigating the expression of these genes in alloimmune-challenged corals are needed to further

  18. Early response in cognitive-behavior therapy for syndromes of medically unexplained symptoms.

    Science.gov (United States)

    Kleinstäuber, Maria; Lambert, Michael J; Hiller, Wolfgang

    2017-05-25

    Early dramatic treatment response suggests a subset of patients who respond to treatment before most of it has been offered. These early responders tend to be over represented among those who are well at termination and at follow-up. Early response patterns in psychotherapy have been investigated only for a few of mental disorders so far. The main aim of the current study was to examine early response after five therapy-preparing sessions of a cognitive behavior therapy (CBT) for syndromes of medically unexplained symptoms (MUS). In the context of a randomized, waiting-list controlled trial 48 patients who suffered from ≥3 MUS over ≥6 months received 5 therapy-preparing sessions and 20 sessions of CBT for somatoform disorders. They completed self-report scales of somatic symptom severity (SOMS-7 T), depression (BDI-II), anxiety (BSI), illness anxiety and behavior (IAS) at pre-treatment, after 5 therapy-preparing sessions (FU-5P) and at therapy termination (FU-20 T). The current analyses are based on data from the treatment arm only. Repeated measure ANOVAs revealed a significant decrease of depression (d = 0.34), anxiety (d = 0.60), illness anxiety (d = 0.38) and illness behavior (d = 0.42), but no change of somatic symptom severity (d = -0.03) between pre-treatment and FU-5P. Hierarchical linear multiple regression analyses showed that symptom improvements between pre-treatment and FU-5P predict a better outcome at therapy termination for depression and illness anxiety, after controlling for pre-treatment scores. Mixed-effect ANOVAs revealed significant group*time interaction effects indicating differences in the course of symptom improvement over the therapy between patients who fulfilled a reliable change (i.e., early response) during the 5 therapy-preparing sessions and patients who did not reach an early reliable change. Demographic or clinical variables at pre-treatment were not significantly correlated with differential scores between pre

  19. Prolonged hypoxia modulates platelet activating factor receptor-mediated responses by fetal ovine pulmonary vascular smooth muscle cells.

    Science.gov (United States)

    Renteria, Lissette S; Raj, J Usha; Ibe, Basil O

    2010-12-01

    Hypoxia augments PAF receptor (PAFr) binding and PAFr protein expression in venous SMC (SMC-PV). We compared effect of acute and prolonged hypoxia (pO(2)<40 torr) on PAFr-mediated responses in arterial SMC (SMC-PA) and SMC-PV. Cells were studied for 30 min (acute) or for 48 h (prolonged) hypoxia and compared to normoxic (pO(2) ~100 torr) conditions. PAF binding was quantified in fmol/10(6) cells (mean ± SEM). PAF binding in normoxia were SMC-PA, 5.2 ± 0.2 and in SMC-PV, 19.3 ± 1.1; values in acute hypoxia were SMC-PA, 7.7 ± 0.4 and in SMC-PV, 27.8 ± 1.7. Prolonged hypoxia produced 6-fold increase in binding in SMC-PA, but only 2-fold increase in SMC-PV, but binding in SMC-PV was still higher. Acute hypoxia augmented inositol phosphate release by 50% and 40% in SMC-PA and SMC-PV, respectively. During normoxia, PAFr mRNA expression by both cell types was similar, but expression in hypoxia by SMC-PA was greater. In SMC-PA, hypoxia and PAF augmented intracellular calcium flux. Re-exposure of cells to 30 min normoxia after 48 h hypoxia decreased binding by 45-60%, suggesting immediate down-regulation of hypoxia-induced PAFr-mediated effects. We speculate that re-oxygenation immediately reverses hypoxia effect probably due to oxygen tension-dependent reversibility of PAFr activation and suggest that exposure of the neonate to prolonged state of hypoxia will vilify oxygen exchange capacity of the neonatal lungs. Copyright © 2010 Elsevier Inc. All rights reserved.

  20. Vascular cell responses to ECM produced by smooth muscle cells on TiO{sub 2} nanotubes

    Energy Technology Data Exchange (ETDEWEB)

    Shen, Fangyu [School of Life Science and Engineering, Southwest Jiaotong University, Chengdu (China); Key Lab of Advanced Technology of Materials of Education Ministry, Southwest Jiaotong University, Chengdu 610031 (China); Zhu, Ying [School of Life Science and Engineering, Southwest Jiaotong University, Chengdu (China); Key Lab of Advanced Technology of Materials of Education Ministry, Southwest Jiaotong University, Chengdu 610031 (China); Wuhan Dragonbio Orthopedic Products CO., LTD, 18, Qinglnghe Road, Hongshan District, Wuhan 430065 (China); Li, Xin [School of Life Science and Engineering, Southwest Jiaotong University, Chengdu (China); Key Lab of Advanced Technology of Materials of Education Ministry, Southwest Jiaotong University, Chengdu 610031 (China); Luo, Rifang, E-mail: lrifang@126.com [School of Life Science and Engineering, Southwest Jiaotong University, Chengdu (China); Key Lab of Advanced Technology of Materials of Education Ministry, Southwest Jiaotong University, Chengdu 610031 (China); Tu, Qiufen [School of Life Science and Engineering, Southwest Jiaotong University, Chengdu (China); Key Lab of Advanced Technology of Materials of Education Ministry, Southwest Jiaotong University, Chengdu 610031 (China); Laboratory of Biosensing and Micro Mechatronics, Southwest Jiaotong University, Chengdu 610031 (China); Wang, Jin, E-mail: jinxxwang@263.net [School of Life Science and Engineering, Southwest Jiaotong University, Chengdu (China); Key Lab of Advanced Technology of Materials of Education Ministry, Southwest Jiaotong University, Chengdu 610031 (China); Huang, Nan [School of Life Science and Engineering, Southwest Jiaotong University, Chengdu (China); Key Lab of Advanced Technology of Materials of Education Ministry, Southwest Jiaotong University, Chengdu 610031 (China)

    2015-09-15

    Graphical abstract: - Highlights: • TiO{sub 2} nanotubes with the tube diameter of 30 nm via anodic oxidation was prepared. • SMCs on TiO{sub 2} nanotubes presented enhanced extracellular matrix secreting. • ECM prepared via decellularization retained the components: Fn, Ln and collagen. • ECM-covered TiO{sub 2} nanotubes significantly improved the proliferation of ECs. - Abstract: There is an increasing interest in developing new methods to promote biocompatibility of biomedical materials. The TiO{sub 2} nanotubes with the tube diameter of 30 nm were prepared by anodization. The response behavior of the human umbilical vein endothelial cell (HUVEC) and human umbilical artery smooth muscle cell (HUASMC) to these different nanotube sizes was investigated. Compared to the flat Ti, the growth and viability of HUVEC are prohibited, but there was no significant difference of HUASMC on 30 nm TiO{sub 2} nanotubes. In this study, extracellular matrix (ECM) as a complex cellular environment which provides structural support to cells and regulates the cells functions was further used to modify the biological properties of TiO{sub 2} nanotubes. The ECM secreted from HUASMC was successfully deposited onto the 30 nm TiO{sub 2} nanotubes. Moreover, immunofluorescence staining of common ECM components, such as fibronectin, laminin and type IV collagen, also indicated the successful ECM-covering on nanotube surfaces. Interestingly, the surface of ECM-covered TiO{sub 2} nanotubes significantly improved the proliferation of HUVECs in vitro. This suggested that the ECM secreted from HUASMCs on the TiO{sub 2} nanotubular surface could further improve the HUVECs adhesion and proliferation.

  1. Malignant gliomas: current perspectives in diagnosis, treatment, and early response assessment using advanced quantitative imaging methods

    Directory of Open Access Journals (Sweden)

    Ahmed R

    2014-03-01

    Full Text Available Rafay Ahmed,1 Matthew J Oborski,2 Misun Hwang,1 Frank S Lieberman,3 James M Mountz11Department of Radiology, 2Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA; 3Department of Neurology and Department of Medicine, Division of Hematology/Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USAAbstract: Malignant gliomas consist of glioblastomas, anaplastic astrocytomas, anaplastic oligodendrogliomas and anaplastic oligoastrocytomas, and some less common tumors such as anaplastic ependymomas and anaplastic gangliogliomas. Malignant gliomas have high morbidity and mortality. Even with optimal treatment, median survival is only 12–15 months for glioblastomas and 2–5 years for anaplastic gliomas. However, recent advances in imaging and quantitative analysis of image data have led to earlier diagnosis of tumors and tumor response to therapy, providing oncologists with a greater time window for therapy management. In addition, improved understanding of tumor biology, genetics, and resistance mechanisms has enhanced surgical techniques, chemotherapy methods, and radiotherapy administration. After proper diagnosis and institution of appropriate therapy, there is now a vital need for quantitative methods that can sensitively detect malignant glioma response to therapy at early follow-up times, when changes in management of nonresponders can have its greatest effect. Currently, response is largely evaluated by measuring magnetic resonance contrast and size change, but this approach does not take into account the key biologic steps that precede tumor size reduction. Molecular imaging is ideally suited to measuring early response by quantifying cellular metabolism, proliferation, and apoptosis, activities altered early in treatment. We expect that successful integration of quantitative imaging biomarker assessment into the early phase of clinical trials could provide a novel approach for testing new therapies

  2. Capturing early signs of deterioration: the dutch-early-nurse-worry-indicator-score and its value in the Rapid Response System.

    Science.gov (United States)

    Douw, Gooske; Huisman-de Waal, Getty; van Zanten, Arthur R H; van der Hoeven, Johannes G; Schoonhoven, Lisette

    2017-09-01

    To determine the predictive value of individual and combined dutch-early-nurse-worry-indicator-score indicators at various Early Warning Score levels, differentiating between Early Warning Scores reaching the trigger threshold to call a rapid response team and Early Warning Score levels not reaching this point. Dutch-early-nurse-worry-indicator-score comprises nine indicators underlying nurses' 'worry' about a patient's condition. All indicators independently show significant association with unplanned intensive care/high dependency unit admission or unexpected mortality. Prediction of this outcome improved by adding the dutch-early-nurse-worry-indicator-score indicators to an Early Warning Score based on vital signs. An observational cohort study was conducted on three surgical wards in a tertiary university-affiliated teaching hospital. Included were surgical, native-speaking, adult patients. Nurses scored presence of 'worry' and/or dutch-early-nurse-worry-indicator-score indicators every shift or when worried. Vital signs were measured according to the prevailing protocol. Unplanned intensive care/high dependency unit admission or unexpected mortality was the composite endpoint. Percentages of 'worry' and dutch-early-nurse-worry-indicator-score indicators were calculated at various Early Warning Score levels in control and event groups. Entering all dutch-early-nurse-worry-indicator-score indicators in a multiple logistic regression analysis, we calculated a weighted score and calculated sensitivity, specificity, positive predicted value and negative predicted value for each possible total score. In 3522 patients, 102 (2·9%) had an unplanned intensive care/high dependency unit admissions (n = 97) or unexpected mortality (n = 5). Patients with such events and only slightly changed vital signs had significantly higher percentages of 'worry' and dutch-early-nurse-worry-indicator-score indicators expressed than patients in the control group. Increasing number

  3. The hypoxia-inducible factor-responsive proteins semaphorin 4D and vascular endothelial growth factor promote tumor growth and angiogenesis in oral squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Hua; Yang, Ying-Hua [Department of Oncology and Diagnostic Sciences, University of Maryland Dental School, 650W. Baltimore Street, 7-North, Baltimore, MD 21201 (United States); Binmadi, Nada O. [Department of Oncology and Diagnostic Sciences, University of Maryland Dental School, 650W. Baltimore Street, 7-North, Baltimore, MD 21201 (United States); Department of Oral Basic and Clinical Sciences, King Abdulaziz University, Jeddah 21589 (Saudi Arabia); Proia, Patrizia [Department of Oncology and Diagnostic Sciences, University of Maryland Dental School, 650W. Baltimore Street, 7-North, Baltimore, MD 21201 (United States); Department of Sports Science (DISMOT), University of Palermo, Via Eleonora Duse 2 90146, Palermo (Italy); Basile, John R., E-mail: jbasile@umaryland.edu [Department of Oncology and Diagnostic Sciences, University of Maryland Dental School, 650W. Baltimore Street, 7-North, Baltimore, MD 21201 (United States); Greenebaum Cancer Center, 22S. Greene Street, Baltimore, MD 21201 (United States)

    2012-08-15

    Growth and metastasis of solid tumors requires induction of angiogenesis to ensure the delivery of oxygen, nutrients and growth factors to rapidly dividing transformed cells. Through either mutations, hypoxia generated by cytoreductive therapies, or when a malignancy outgrows its blood supply, tumor cells undergo a change from an avascular to a neovascular phenotype, a transition mediated by the hypoxia-inducible factor (HIF) family of transcriptional regulators. Vascular endothelial growth factor (VEGF) is one example of a gene whose transcription is stimulated by HIF. VEGF plays a crucial role in promoting tumor growth and survival by stimulating new blood vessel growth in response to such stresses as chemotherapy or radiotherapy-induced hypoxia, and it therefore has become a tempting target for neutralizing antibodies in the treatment of advanced neoplasms. Emerging evidence has shown that the semaphorins, proteins originally associated with control of axonal growth and immunity, are regulated by changes in oxygen tension as well and may play a role in tumor-induced angiogenesis. Through the use of RNA interference, in vitro and in vivo angiogenesis assays and tumor xenograft experiments, we demonstrate that expression of semaphorin 4D (SEMA4D), which is under the control of the HIF-family of transcription factors, cooperates with VEGF to promote tumor growth and vascularity in oral squamous cell carcinoma (OSCC). We use blocking antibodies to show that targeting SEMA4D function along with VEGF could represent a novel anti-angiogenic therapeutic strategy for the treatment of OSCC and other solid tumors. -- Highlights: Black-Right-Pointing-Pointer Similar to VEGF, SEMA4D promotes angiogenesis in vitro and in vivo. Black-Right-Pointing-Pointer Both VEGF and SEMA4D are produced by OSCC cells in a HIF-dependent manner. Black-Right-Pointing-Pointer These factors combine to elicit a robust pro-angiogenic phenotype in OSCC. Black-Right-Pointing-Pointer Anti-SEMA4D

  4. The hypoxia-inducible factor-responsive proteins semaphorin 4D and vascular endothelial growth factor promote tumor growth and angiogenesis in oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Zhou, Hua; Yang, Ying-Hua; Binmadi, Nada O.; Proia, Patrizia; Basile, John R.

    2012-01-01

    Growth and metastasis of solid tumors requires induction of angiogenesis to ensure the delivery of oxygen, nutrients and growth factors to rapidly dividing transformed cells. Through either mutations, hypoxia generated by cytoreductive therapies, or when a malignancy outgrows its blood supply, tumor cells undergo a change from an avascular to a neovascular phenotype, a transition mediated by the hypoxia-inducible factor (HIF) family of transcriptional regulators. Vascular endothelial growth factor (VEGF) is one example of a gene whose transcription is stimulated by HIF. VEGF plays a crucial role in promoting tumor growth and survival by stimulating new blood vessel growth in response to such stresses as chemotherapy or radiotherapy-induced hypoxia, and it therefore has become a tempting target for neutralizing antibodies in the treatment of advanced neoplasms. Emerging evidence has shown that the semaphorins, proteins originally associated with control of axonal growth and immunity, are regulated by changes in oxygen tension as well and may play a role in tumor-induced angiogenesis. Through the use of RNA interference, in vitro and in vivo angiogenesis assays and tumor xenograft experiments, we demonstrate that expression of semaphorin 4D (SEMA4D), which is under the control of the HIF-family of transcription factors, cooperates with VEGF to promote tumor growth and vascularity in oral squamous cell carcinoma (OSCC). We use blocking antibodies to show that targeting SEMA4D function along with VEGF could represent a novel anti-angiogenic therapeutic strategy for the treatment of OSCC and other solid tumors. -- Highlights: ► Similar to VEGF, SEMA4D promotes angiogenesis in vitro and in vivo. ► Both VEGF and SEMA4D are produced by OSCC cells in a HIF-dependent manner. ► These factors combine to elicit a robust pro-angiogenic phenotype in OSCC. ► Anti-SEMA4D blocking antibody inhibits Plexin-B1 activation. ► SEMA4D is a valid anti-angiogenic target in the

  5. A New Experimental Polytrauma Model in Rats: Molecular Characterization of the Early Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Sebastian Weckbach

    2012-01-01

    Full Text Available Background. The molecular mechanisms of the immune response after polytrauma are highly complex and far from fully understood. In this paper, we characterize a new standardized polytrauma model in rats based on the early molecular inflammatory and apoptotic response. Methods. Male Wistar rats (250 g, 6–10/group were anesthetized and exposed to chest trauma (ChT, closed head injury (CHI, or Tib/Fib fracture including a soft tissue trauma (Fx + STT or to the following combination of injuries: (1 ChT; (2 ChT + Fx + STT; (3 ChT + CHI; (4 CHI; (5 polytrauma (PT = ChT + CHI + Fx + STT. Sham-operated rats served as negative controls. The inflammatory response was quantified at 2 hours and 4 hours after trauma by analysis of “key” inflammatory mediators, including selected cytokines and complement components, in serum and bronchoalveolar (BAL fluid samples. Results. Polytraumatized (PT rats showed a significant systemic and intrapulmonary release of cytokines, chemokines, and complement anaphylatoxins, compared to rats with isolated injuries or selected combinations of injuries. Conclusion. This new rat model appears to closely mimic the early immunological response of polytrauma observed in humans and may provide a valid basis for evaluation of the complex pathophysiology and future therapeutic immune modulatory approaches in experimental polytrauma.

  6. A New Experimental Polytrauma Model in Rats: Molecular Characterization of the Early Inflammatory Response

    Science.gov (United States)

    Weckbach, Sebastian; Perl, Mario; Heiland, Tim; Braumüller, Sonja; Stahel, Philip F.; Flierl, Michael A.; Ignatius, Anita; Gebhard, Florian; Huber-Lang, Markus

    2012-01-01

    Background. The molecular mechanisms of the immune response after polytrauma are highly complex and far from fully understood. In this paper, we characterize a new standardized polytrauma model in rats based on the early molecular inflammatory and apoptotic response. Methods. Male Wistar rats (250 g, 6–10/group) were anesthetized and exposed to chest trauma (ChT), closed head injury (CHI), or Tib/Fib fracture including a soft tissue trauma (Fx + STT) or to the following combination of injuries: (1) ChT; (2) ChT + Fx + STT; (3) ChT + CHI; (4) CHI; (5) polytrauma (PT = ChT + CHI + Fx + STT). Sham-operated rats served as negative controls. The inflammatory response was quantified at 2 hours and 4 hours after trauma by analysis of “key” inflammatory mediators, including selected cytokines and complement components, in serum and bronchoalveolar (BAL) fluid samples. Results. Polytraumatized (PT) rats showed a significant systemic and intrapulmonary release of cytokines, chemokines, and complement anaphylatoxins, compared to rats with isolated injuries or selected combinations of injuries. Conclusion. This new rat model appears to closely mimic the early immunological response of polytrauma observed in humans and may provide a valid basis for evaluation of the complex pathophysiology and future therapeutic immune modulatory approaches in experimental polytrauma. PMID:22481866

  7. Temperament and Parenting Styles in Early Childhood Differentially Influence Neural Response to Peer Evaluation in Adolescence

    Science.gov (United States)

    Guyer, Amanda E.; Jarcho, Johanna M.; Pérez-Edgar, Koraly; Degnan, Kathryn A.; Pine, Daniel S.; Fox, Nathan A.; Nelson, Eric E.

    2015-01-01

    Behavioral inhibition (BI) is a temperament characterized by social reticence and withdrawal from unfamiliar or novel contexts and conveys risk for social anxiety disorder. Developmental outcomes associated with this temperament can be influenced by children’s caregiving context. The convergence of a child’s temperamental disposition and rearing environment is ultimately expressed at both the behavioral and neural levels in emotional and cognitive response patterns to social challenges. The present study used functional neuroimaging to assess the moderating effects of different parenting styles on neural response to peer rejection in two groups of adolescents characterized by their early childhood temperament (Mage = 17.89 years, N= 39, 17 males, 22 females; 18 with BI; 21 without BI). The moderating effects of authoritarian and authoritative parenting styles were examined in three brain regions linked with social anxiety: ventrolateral prefrontal cortex (vlPFC), striatum, and amygdala. In youth characterized with BI in childhood, but not in those without BI, diminished responses to peer rejection in vlPFC were associated with higher levels of authoritarian parenting. In contrast, all youth showed decreased caudate response to peer rejection at higher levels of authoritative parenting. These findings indicate that BI in early life relates to greater neurobiological sensitivity to variance in parenting styles, particularly harsh parenting, in late adolescence. These results are discussed in relation to biopsychosocial models of development. PMID:25588884

  8. Temperament and Parenting Styles in Early Childhood Differentially Influence Neural Response to Peer Evaluation in Adolescence.

    Science.gov (United States)

    Guyer, Amanda E; Jarcho, Johanna M; Pérez-Edgar, Koraly; Degnan, Kathryn A; Pine, Daniel S; Fox, Nathan A; Nelson, Eric E

    2015-07-01

    Behavioral inhibition (BI) is a temperament characterized by social reticence and withdrawal from unfamiliar or novel contexts and conveys risk for social anxiety disorder. Developmental outcomes associated with this temperament can be influenced by children's caregiving context. The convergence of a child's temperamental disposition and rearing environment is ultimately expressed at both the behavioral and neural levels in emotional and cognitive response patterns to social challenges. The present study used functional neuroimaging to assess the moderating effects of different parenting styles on neural response to peer rejection in two groups of adolescents characterized by their early childhood temperament (M(age) = 17.89 years, N = 39, 17 males, 22 females; 18 with BI; 21 without BI). The moderating effects of authoritarian and authoritative parenting styles were examined in three brain regions linked with social anxiety: ventrolateral prefrontal cortex (vlPFC), striatum, and amygdala. In youth characterized with BI in childhood, but not in those without BI, diminished responses to peer rejection in vlPFC were associated with higher levels of authoritarian parenting. In contrast, all youth showed decreased caudate response to peer rejection at higher levels of authoritative parenting. These findings indicate that BI in early life relates to greater neurobiological sensitivity to variance in parenting styles, particularly harsh parenting, in late adolescence. These results are discussed in relation to biopsychosocial models of development.

  9. Exposure to Violence Predicting Cortisol Response During Adolescence and Early Adulthood: Understanding Moderating Factors

    Science.gov (United States)

    Heinze, Justin E.; Miller, Alison L.; Stoddard, Sarah A.; Zimmerman, Marc A.

    2014-01-01

    Previous research on the association between violence and biological stress regulation has been largely cross-sectional, and has also focused on childhood. Using longitudinal data from a low-income, high-risk, predominantly African-American sample (n = 266; 57 % female), we tested hypotheses about the influence of cumulative exposure to violence during adolescence and early adulthood on cortisol responses in early adulthood. We found that cumulative exposure to violence predicted an attenuated cortisol response. Further, we tested whether sex, mothers’ support, or fathers’ support moderated the effect of exposure to violence on cortisol responses. We found that the effect of cumulative exposure to violence on cortisol was modified by sex; specifically, males exposed to violence exhibited a more attenuated response pattern. In addition, the effect of cumulative exposure to violence on cortisol was moderated by the presence of fathers’ support during adolescence. The findings contribute to a better understanding of how cumulative exposure to violence influences biological outcomes, emphasizing the need to understand sex and parental support as moderators of risk. PMID:24458765

  10. Diabetes diminishes the portal-systemic collateral vascular response to vasopressin via vasopressin receptor and Gα proteins regulations in cirrhotic rats.

    Directory of Open Access Journals (Sweden)

    Jing-Yi Lee

    Full Text Available Liver cirrhosis may lead to portal-systemic collateral formation and bleeding. The hemostatic effect is influenced by the response of collateral vessels to vasoconstrictors. Diabetes and glucose also influence vasoresponsiveness, but their net effect on collaterals remains unexplored. This study investigated the impact of diabetes or glucose application on portal-systemic collateral vasoresponsiveness to arginine vasopressin (AVP in cirrhosis. Spraque-Dawley rats with bile duct ligation (BDL-induced cirrhosis received vehicle (citrate buffer or streptozotocin (diabetic, BDL/STZ. The in situ collateral perfusion was done after hemodynamic measurements: Both were perfused with Krebs solution, D-glucose, or D-glucose and NaF, with additional OPC-31260 for the BDL/STZ group. Splenorenal shunt vasopressin receptors and Gα proteins mRNA expressions were evaluated. The survival rate of cirrhotic rats was decreased by STZ injection. The collateral perfusion pressure changes to AVP were lower in STZ-injected groups, which were reversed by OPC-31260 (a V2R antagonist and overcome by NaF (a G protein activator. The splenorenal shunt V2R mRNA expression was increased while Gα proteins mRNA expressions were decreased in BDL/STZ rats compared to BDL rats. The Gαq and Gα11 mRNA expressions also correlated with the maximal perfusion pressure changes to AVP. Diabetes diminished the portal-systemic collateral vascular response to AVP in rats with BDL-induced cirrhosis, probably via V2 receptor up-regulation and Gα proteins down-regulation.

  11. Glycogen synthase kinase 3β regulation of nuclear factor of activated T-cells isoform c1 in the vascular smooth muscle cell response to injury

    International Nuclear Information System (INIS)

    Chow Winsion; Hou Guangpei; Bendeck, Michelle P.

    2008-01-01

    The migration and proliferation of vascular smooth muscle cells (vSMCs) are critical events in neointima formation during atherosclerosis and restenosis. The transcription factor nuclear factor of activated T-cells-isoform c1 (NFATc1) is regulated by atherogenic cytokines, and has been implicated in the migratory and proliferative responses of vSMCs through the regulation of gene expression. In T-cells, calcineurin de-phosphorylates NFATc1, leading to its nuclear import, while glycogen synthase kinase 3 β (GSK3β) phosphorylates NFATc1 and promotes its nuclear export. However, the relationship between NFATc1 and GSK3β has not been studied during SMC migration and proliferation. We investigated this by scrape wounding vSMCs in vitro, and studying wound repair. NFATc1 protein was transiently increased, reaching a peak at 8 h after wounding. Cell fractionation and immunocytochemistry revealed that NFATc1 accumulation in the nucleus was maximal at 4 h after injury, and this was coincident with a significant 9 fold increase in transcriptional activity. Silencing NFATc1 expression with siRNA or inhibition of NFAT with cyclosporin A (CsA) attenuated wound closure by vSMCs. Phospho-GSK3β (inactive) increased to a peak at 30 min after injury, preceding the nuclear accumulation of NFATc1. Overexpression of a constitutively active mutant of GSK3β delayed the nuclear accumulation of NFATc1, caused a 50% decrease in NFAT transcriptional activity, and attenuated vSMC wound repair. We conclude that NFATc1 promotes the vSMC response to injury, and that inhibition of GSK3β is required for the activation of NFAT during wound repair

  12. Angiogenesis, Cancer, and Vascular Aging

    Directory of Open Access Journals (Sweden)

    Junji Moriya

    2017-10-01

    Full Text Available Several lines of evidence have revealed that the angiogenic response to ischemic injury declines with age, which might account for the increased morbidity and mortality of cardiovascular disease (CVD among the elderly. While impairment of angiogenesis with aging leads to delayed wound healing or exacerbation of atherosclerotic ischemic diseases, it also inhibits the progression of cancer. Age-related changes of angiogenesis have been considered to at least partly result from vascular aging or endothelial cell senescence. There is considerable evidence supporting the hypothesis that vascular cell senescence contributes to the pathogenesis of age-related CVD, suggesting that vascular aging could be an important therapeutic target. Since therapeutic angiogenesis is now regarded as a promising concept for patients with ischemic CVD, it has become even more important to understand the detailed molecular mechanisms underlying impairment of angiogenesis in older patients. To improve the usefulness of therapeutic angiogenesis, approaches are needed that can compensate for impaired angiogenic capacity in the elderly while not promoting the development or progression of malignancy. In this review, we briefly outline the mechanisms of angiogenesis and vascular aging, followed by a description of how vascular aging leads to impairment of angiogenesis. We also examine potential therapeutic approaches that could enhance angiogenesis and/or vascular function in the elderly, as well as discussing the possibility of anti-senescence therapy or reversal of endothelial cell senescence.

  13. Early print-tuned ERP response with minimal involvement of linguistic processing in Japanese Hiragana strings.

    Science.gov (United States)

    Okumura, Yasuko; Kasai, Tetsuko; Murohashi, Harumitsu

    2014-04-16

    The act of reading leads to the development of specific neural responses for print, the most frequently reported of which is the left occipitotemporal N170 component of event-related potentials. However, it remains unclear whether this electrophysiological response solely involves print-tuned neural activities. The present study examined an early print-tuned event-related potential response with minimal involvement of linguistic processing in a nonalphabetic language. Japanese Hiragana words, nonwords, and alphanumeric symbol strings were presented rapidly and the task was to detect the change in color of a fixation cross to restrict linguistic processing. As a result, Hiragana words and nonwords elicited a larger posterior N1 than alphanumeric symbol strings bilaterally, irrespective of intercharacter spacing. The fact that this N1 was enhanced specifically for rapidly presented Hiragana strings suggests the existence of print-tuned neural processes that are relatively independent of the influence of linguistic processing.

  14. Jasmonate signaling is activated in the very early stages of iron deficiency responses in rice roots.

    Science.gov (United States)

    Kobayashi, Takanori; Itai, Reiko Nakanishi; Senoura, Takeshi; Oikawa, Takaya; Ishimaru, Yasuhiro; Ueda, Minoru; Nakanishi, Hiromi; Nishizawa, Naoko K

    2016-07-01

    Under low iron availability, plants induce the expression of various genes involved in iron uptake and translocation at the transcriptional level. This iron deficiency response is affected by various plant hormones, but the roles of jasmonates in this response are not well-known. We investigated the involvement of jasmonates in rice iron deficiency responses. High rates of jasmonate-inducible genes were induced during the very early stages of iron deficiency treatment in rice roots. Many jasmonate-inducible genes were also negatively regulated by the ubiquitin ligases OsHRZ1 and OsHRZ2 and positively regulated by the transcription factor IDEF1. Ten out of 35 genes involved in jasmonate biosynthesis and signaling were rapidly induced at 3 h of iron deficiency treatment, and this induction preceded that of known iron deficiency-inducible genes involved in iron uptake and translocation. Twelve genes involved in jasmonate biosynthesis and signaling were also upregulated in HRZ-knockdown roots. Endogenous concentrations of jasmonic acid and jasmonoyl isoleucine tended to be rapidly increased in roots in response to iron deficiency treatment, whereas these concentrations were higher in HRZ-knockdown roots under iron-sufficient conditions. Analysis of the jasmonate-deficient cpm2 mutant revealed that jasmonates repress the expression of many iron deficiency-inducible genes involved in iron uptake and translocation under iron sufficiency, but this repression is partly canceled under an early stage of iron deficiency. These results indicate that jasmonate signaling is activated during the very early stages of iron deficiency, which is partly regulated by IDEF1 and OsHRZs.

  15. Comparative responses to endocrine disrupting compounds in early life stages of Atlantic salmon, Salmo salar

    Science.gov (United States)

    Duffy, Tara A.; Iwanowicz, Luke R.; McCormick, Stephen D.

    2014-01-01

    Atlantic salmon (Salmo salar) are endangered anadromous fish that may be exposed to feminizing endocrine disrupting compounds (EDCs) during early development, potentially altering physiological capacities, survival and fitness. To assess differential life stage sensitivity to common EDCs, we carried out short-term (four day) exposures using three doses each of 17α-ethinylestradiol (EE2), 17β-estradiol (E2), and nonylphenol (NP) on four early life stages; embryos, yolk-sac larvae, feeding fry and one year old smolts. Differential response was compared using vitellogenin (Vtg, a precursor egg protein) gene transcription. Smolts were also examined for impacts on plasma Vtg, cortisol, thyroid hormones (T4/T3) and hepatosomatic index (HSI). Compound-related mortality was not observed in any life stage, but Vtg mRNA was elevated in a dose-dependent manner in yolk-sac larvae, fry and smolts but not in embyos. The estrogens EE2 and E2 were consistently stronger inducers of Vtg than NP. Embryos responded significantly to the highest concentration of EE2 only, while older life stages responded to the highest doses of all three compounds, as well as intermediate doses of EE2 and E2. Maximal transcription was greater for fry among the three earliest life stages, suggesting fry may be the most responsive life stage in early development. Smolt plasma Vtg was also significantly increased, and this response was observed at lower doses of each compound than was detected by gene transcription suggesting this is a more sensitive indicator at this life stage. HSI was increased at the highest doses of EE2 and E2 and plasma T3 decreased at the highest dose of EE2. Our results indicate that all life stages after hatching are potentially sensitive to endocrine disruption by estrogenic compounds and that physiological responses were altered over a short window of exposure, indicating the potential for these compounds to impact fish in the wild.

  16. Energy input and response from prompt and early optical afterglow emission in gamma-ray bursts.

    Science.gov (United States)

    Vestrand, W T; Wren, J A; Wozniak, P R; Aptekar, R; Golentskii, S; Pal'shin, V; Sakamoto, T; White, R R; Evans, S; Casperson, D; Fenimore, E

    2006-07-13

    The taxonomy of optical emission detected during the critical first few minutes after the onset of a gamma-ray burst (GRB) defines two broad classes: prompt optical emission correlated with prompt gamma-ray emission, and early optical afterglow emission uncorrelated with the gamma-ray emission. The standard theoretical interpretation attributes prompt emission to internal shocks in the ultra-relativistic outflow generated by the internal engine; early afterglow emission is attributed to shocks generated by interaction with the surrounding medium. Here we report on observations of a bright GRB that, for the first time, clearly show the temporal relationship and relative strength of the two optical components. The observations indicate that early afterglow emission can be understood as reverberation of the energy input measured by prompt emission. Measurements of the early afterglow reverberations therefore probe the structure of the environment around the burst, whereas the subsequent response to late-time impulsive energy releases reveals how earlier flaring episodes have altered the jet and environment parameters. Many GRBs are generated by the death of massive stars that were born and died before the Universe was ten per cent of its current age, so GRB afterglow reverberations provide clues about the environments around some of the first stars.

  17. Recognition of Immune Response for the Early Diagnosis and Treatment of Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Adrese M. Kandahari

    2015-01-01

    Full Text Available Osteoarthritis is a common and debilitating joint disease that affects up to 30 million Americans, leading to significant disability, reduction in quality of life, and costing the United States tens of billions of dollars annually. Classically, osteoarthritis has been characterized as a degenerative, wear-and-tear disease, but recent research has identified it as an immunopathological disease on a spectrum between healthy condition and rheumatoid arthritis. A systematic literature review demonstrates that the disease pathogenesis is driven by an early innate immune response which progressively catalyzes degenerative changes that ultimately lead to an altered joint microenvironment. It is feasible to detect this infiltration of cells in the early, and presumably asymptomatic, phase of the disease through noninvasive imaging techniques. This screening can serve to aid clinicians in potentially identifying high-risk patients, hopefully leading to early effective management, vast improvements in quality of life, and significant reductions in disability, morbidity, and cost related to osteoarthritis. Although the diagnosis and treatment of osteoarthritis routinely utilize both invasive and non-invasive strategies, imaging techniques specific to inflammatory cells are not commonly employed for these purposes. This review discusses this paradigm and aims to shift the focus of future osteoarthritis-related research towards early diagnosis of the disease process.

  18. Injuries to the vascular endothelium: vascular wall and endothelial dysfunction.

    Science.gov (United States)

    Fisher, Mark

    2008-01-01

    Vascular endothelial injury has multiple elements, and this article focuses on ischemia-related processes that have particular relevance to ischemic stroke. Distinctions between necrotic and apoptotic cell death provide a basic science context in which to better understand the significance of classical core and penumbra concepts of acute stroke, with apoptotic processes particularly prominent in the penumbra. The mitochondria are understood to serve as a reservoir of proteins that mediate apoptosis. Oxidative stress pathways generating reactive oxygen species (ROS) are prominent in endothelial injury, both ischemic and nonischemic, with prominent roles of enzyme- and nonenzymemediated pathways; mitochondria once again have a critical role, particularly in the nonenzymatic pathways generating ROS. Inflammation also contributes to vascular endothelial injury, and endothelial cells have the capacity to rapidly increase expression of inflammatory mediators following ischemic challenge; this leads to enhanced leukocyte-endothelial interactions mediated by selectins and adhesion molecules. Preconditioning consists of a minor version of an injurious event, which in turn may protect vascular endothelium from injury following a more substantial event. Presence of the blood-brain barrier creates unique responses to endothelial injury, with permeability changes due to impairment of endothelial-matrix interactions compounding altered vasomotor tone and tissue perfusion mediated by nitric oxide. Pharmacological protection against vascular endothelial injury can be provided by several of the phosphodiesterases (cilostazol and dipyridamole), along with statins. Optimal clinical responses for protection of brain vascular endothelium may use preconditioning as a model, and will likely require combined protection against apoptosis, ROS, and inflammation.

  19. Responsive parenting: establishing early foundations for social, communication, and independent problem-solving skills.

    Science.gov (United States)

    Landry, Susan H; Smith, Karen E; Swank, Paul R

    2006-07-01

    Mothers whose infants varied in early biological characteristics (born at term, n = 120; born at very low birth weight [VLBW], n = 144) were randomized to a target group (n = 133) or developmental feedback comparison group (n = 131) to determine whether learning responsive behaviors would facilitate infant development. The target condition included videotaped examples, problem-solving activities, and mothers' critique of their own behaviors through video procedures across 10 home visits. All target versus comparison mothers showed greater increases across multiple responsiveness behaviors observed in 4 assessments conducted across 6-13 months of age; changes in emotionally supportive behaviors were strongest for target mothers of infants born at VLBW. Increased maternal responsiveness facilitated greater growth in target infants' social, emotional, communication, and cognitive competence, supporting a causal role for responsiveness on infant development. Although benefits were generally comparable across risk groups, aspects of social and emotional skills showed greater change for those born at VLBW. Evidence for responsiveness as a multidimensional construct was provided as well as the importance of different aspects of responsiveness mediating the effect of the intervention on different infant skill domains.

  20. Response of the sensorimotor cortex of cerebral palsy rats receiving transplantation of vascular endothelial growth factor 165-transfected neural stem cells

    Institute of Scientific and Technical Information of China (English)

    Jielu Tan; Xiangrong Zheng; Shanshan Zhang; Yujia Yang; Xia Wang; Xiaohe Yu; Le Zhong

    2014-01-01

    Neural stem cells are characterized by the ability to differentiate and stably express exogenous ge-nes. Vascular endothelial growth factor plays a role in protecting local blood vessels and neurons of newborn rats with hypoxic-ischemic encephalopathy. Transplantation of vascular endothelial growth factor-transfected neural stem cells may be neuroprotective in rats with cerebral palsy. In this study, 7-day-old Sprague-Dawley rats were divided into ifve groups: (1) sham operation (control), (2) cerebral palsy model alone or with (3) phosphate-buffered saline, (4) vascular en-dothelial growth factor 165 + neural stem cells, or (5) neural stem cells alone. hTe cerebral palsy model was established by ligating the letf common carotid artery followed by exposure to hypox-ia. Phosphate-buffered saline, vascular endothelial growth factor + neural stem cells, and neural stem cells alone were administered into the sensorimotor cortex using the stereotaxic instrument and microsyringe. Atfer transplantation, the radial-arm water maze test and holding test were performed. Immunohistochemistry for vascular endothelial growth factor and histology using hematoxylin-eosin were performed on cerebral cortex. Results revealed that the number of vas-cular endothelial growth factor-positive cells in cerebral palsy rats transplanted with vascular endothelial growth factor-transfected neural stem cells was increased, the time for ifnding water and the ifnding repetitions were reduced, the holding time was prolonged, and the degree of cell degeneration or necrosis was reduced. hTese ifndings indicate that the transplantation of vascu-lar endothelial growth factor-transfected neural stem cells alleviates brain damage and cognitive deifcits, and is neuroprotective in neonatal rats with hypoxia ischemic-mediated cerebral palsy.

  1. The temporal relationship between reduction of early imitative responses and the development of attention mechanisms

    Directory of Open Access Journals (Sweden)

    Benga Oana

    2003-12-01

    Full Text Available Abstract Background To determine whether early imitative responses fade out following the maturation of attentional mechanisms, the relationship between primitive imitation behaviors and the development of attention was examined in 4-month-old infants. They were divided into high and low imitators, based on an index of imitation. The status of attention was assessed by studying inhibition of return (IOR. Nine-month-old infants were also tested to confirm the hypothesis. Results The IOR latency data replicate previous results that infants get faster to produce a covert shift of attention with increasing age. However, those 4-month-olds who showed less imitation had more rapid saccades to the cue before target presentation. Conclusion The cortical control of saccade planning appears to be related to an apparent drop in early imitation. We interpret the results as suggesting a relationship between the status of imitation and the neural development of attention-related eye movement.

  2. Real-Time Surveillance in Emergencies Using the Early Warning Alert and Response Network.

    Science.gov (United States)

    Cordes, Kristina M; Cookson, Susan T; Boyd, Andrew T; Hardy, Colleen; Malik, Mamunur Rahman; Mala, Peter; El Tahir, Khalid; Everard, Marthe; Jasiem, Mohamad; Husain, Farah

    2017-11-01

    Humanitarian emergencies often result in population displacement and increase the risk for transmission of communicable diseases. To address the increased risk for outbreaks during humanitarian emergencies, the World Health Organization developed the Early Warning Alert and Response Network (EWARN) for early detection of epidemic-prone diseases. The US Centers for Disease Control and Prevention has worked with the World Health Organization, ministries of health, and other partners to support EWARN through the implementation and evaluation of these systems and the development of standardized guidance. Although protocols have been developed for the implementation and evaluation of EWARN, a need persists for standardized training and additional guidance on supporting these systems remotely when access to affected areas is restricted. Continued collaboration between partners and the Centers for Disease Control and Prevention for surveillance during emergencies is necessary to strengthen capacity and support global health security.

  3. Genetic Regulation of Vascular Development: Building the Zebrafish Vascular Tree

    NARCIS (Netherlands)

    R.L.J.M. Herpers (Robert)

    2010-01-01

    textabstractThe extensive networks of blood and lymphatic vessels within the vertebrate body are essential for the transport and delivery of fluids, gases, macromolecules and cells, and play important roles in facilitating immune responses. The development of the vascular tree requires a highly

  4. Regulation of early and delayed radiation responses in rat small intestine by capsaicin-sensitive nerves

    International Nuclear Information System (INIS)

    Wang Junru; Zheng Huaien; Kulkarni, Ashwini; Ou Xuemei; Hauer-Jensen, Martin

    2006-01-01

    Purpose: Mast cells protect against the early manifestations of intestinal radiation toxicity, but promote chronic intestinal wall fibrosis. Intestinal sensory nerves are closely associated with mast cells, both anatomically and functionally, and serve an important role in the regulation of mucosal homeostasis. This study examined the effect of sensory nerve ablation on the intestinal radiation response in an established rat model. Methods and Materials: Rats underwent sensory nerve ablation with capsaicin or sham ablation. Two weeks later, a localized segment of ileum was X-irradiated or sham irradiated. Structural, cellular, and molecular changes were examined 2 weeks (early injury) and 26 weeks (chronic injury) after irradiation. The mast cell dependence of the effect of sensory nerve ablation on intestinal radiation injury was assessed using c-kit mutant (Ws/Ws) mast cell-deficient rats. Results: Capsaicin treatment caused a baseline reduction in mucosal mast cell density, crypt cell proliferation, and expression of substance P and calcitonin gene-related peptide, two neuropeptides released by sensory neurons. Sensory nerve ablation strikingly exacerbated early intestinal radiation toxicity (loss of mucosal surface area, inflammation, intestinal wall thickening), but attenuated the development of chronic intestinal radiation fibrosis (collagen I accumulation and transforming growth factor β immunoreactivity). In mast cell-deficient rats, capsaicin treatment exacerbated postradiation epithelial injury (loss of mucosal surface area), but none of the other aspects of radiation injury were affected by capsaicin treatment. Conclusions: Ablation of capsaicin-sensitive enteric neurons exacerbates early intestinal radiation toxicity, but attenuates development of chronic fibroproliferative changes. The effect of capsaicin treatment on the intestinal radiation response is partly mast cell dependent

  5. Impaired early visual response modulations to spatial information in chronic schizophrenia

    Science.gov (United States)

    Knebel, Jean-François; Javitt, Daniel C.; Murray, Micah M.

    2011-01-01

    Early visual processing stages have been demonstrated to be impaired in schizophrenia patients and their first-degree relatives. The amplitude and topography of the P1 component of the visual evoked potential (VEP) are both affected; the latter of which indicates alterations in active brain networks between populations. At least two issues remain unresolved. First, the specificity of this deficit (and suitability as an endophenotype) has yet to be established, with evidence for impaired P1 responses in other clinical populations. Second, it remains unknown whether schizophrenia patients exhibit intact functional modulation of the P1 VEP component; an aspect that may assist in distinguishing effects specific to schizophrenia. We applied electrical neuroimaging analyses to VEPs from chronic schizophrenia patients and healthy controls in response to variation in the parafoveal spatial extent of stimuli. Healthy controls demonstrated robust modulation of the VEP strength and topography as a function of the spatial extent of stimuli during the P1 component. By contrast, no such modulations were evident at early latencies in the responses from patients with schizophrenia. Source estimations localized these deficits to the left precuneus and medial inferior parietal cortex. These findings provide insights on potential underlying low-level impairments in schizophrenia. PMID:21764264

  6. Developmental changes in mismatch responses to mandarin consonants and lexical tones from early to middle childhood.

    Directory of Open Access Journals (Sweden)

    Huei-Mei Liu

    Full Text Available The purpose of this study was to use mismatch responses (MMRs to explore the dynamic changes of Mandarin speech perception abilities from early to middle childhood. Twenty preschoolers, 18 school-aged children, and 26 adults participated in this study. Two sets of synthesized speech stimuli varying in Mandarin consonant (alveolo-palatal affricate vs. fricative and lexical tone features (rising vs. contour tone were used to examine the developmental course of speech perception abilities. The results indicated that only the adult group demonstrated typical early mismatch negativity (MMN responses, suggesting that the ability to discriminate specific speech cues in Mandarin consonant and lexical tone is a continuing process in preschool- and school-aged children. Additionally, distinct MMR patterns provided evidence indicating diverse developmental courses to different speech characteristics. By incorporating data from the two speech conditions, we propose using MMR profiles consisting of mismatch negativity (MMN, positive mismatch response (p-MMR, and late discriminative negativity (LDN as possible brain indices to investigate speech perception development.

  7. FDG PET/CT in initial staging and early response to chemotherapy assessment of paediatric rhabdomyosarcomas

    International Nuclear Information System (INIS)

    Eugene, T.; Ansquer, C.; Oudoux, A.; Carlier, T.; Kraeber-Bodere, T.; Bodet-Milin, C.; Corradini, N.; Thomas, C.; Dupas, B.

    2010-01-01

    Purpose: The objective of this study was to retrospectively evaluate the impact of positron emission tomography/computed tomography (PET/CT) using fluorine-18-fluorodeoxyglucose (FDG), in comparison with conventional imaging modalities (CIM), for initial staging and early therapy assessment in paediatric rhabdomyosarcoma. Patients and methods: Prior to treatment, 18 patients (age range, 9 months to 18 years) with histologically proven rhabdomyosarcoma underwent FDG PET/CT in addition to CIM (magnetic resonance imaging of primary site, whole body CT and bone scintigraphy). After three courses of chemotherapy, 12 patients underwent FDG PET/CT in addition to CIM. RECIST criteria and visual analysis of FDG uptake were used for assessment of response. The standard of reference was determined by an interdisciplinary tumor board based on imaging material, histopathology and follow-up data (median = 5 years). Results: PET/CT sensitivity was superior to CIM's concerning lymph node involvement (100% versus 83%, respectively) and metastases detection (100% versus 50%, respectively). PET/CT results changed therapeutic management in 11% of cases. After three courses of chemotherapy, the rate of complete response was 66% with PET/CT versus 8% with CIM. Five percent of patients relapsed during follow-up (median = 5 years). Conclusion: This study confirms that PET/CT depicts important additional information in initial staging of paediatric rhabdomyosarcomas and suggests a superior prognostic value of PET/CT in early response to chemotherapy assessment. (authors)

  8. The p66(Shc adaptor protein controls oxidative stress response in early bovine embryos.

    Directory of Open Access Journals (Sweden)

    Dean H Betts

    Full Text Available The in vitro production of mammalian embryos suffers from high frequencies of developmental failure due to excessive levels of permanent embryo arrest and apoptosis caused by oxidative stress. The p66Shc stress adaptor protein controls oxidative stress response of somatic cells by regulating intracellular ROS levels through multiple pathways, including mitochondrial ROS generation and the repression of antioxidant gene expression. We have previously demonstrated a strong relationship with elevated p66Shc levels, reduced antioxidant levels and greater intracellular ROS generation with the high incidence of permanent cell cycle arrest of 2-4 cell embryos cultured under high oxygen tensions or after oxidant treatment. The main objective of this study was to establish a functional role for p66Shc in regulating the oxidative stress response during early embryo development. Using RNA interference in bovine zygotes we show that p66Shc knockdown embryos exhibited increased MnSOD levels, reduced intracellular ROS and DNA damage that resulted in a greater propensity for development to the blastocyst stage. P66Shc knockdown embryos were stress resistant exhibiting significantly reduced intracellular ROS levels, DNA damage, permanent 2-4 cell embryo arrest and diminished apoptosis frequencies after oxidant treatment. The results of this study demonstrate that p66Shc controls the oxidative stress response in early mammalian embryos. Small molecule inhibition of p66Shc may be a viable clinical therapy to increase the developmental potential of in vitro produced mammalian embryos.

  9. Transcriptome Analysis of Early Responsive Genes in Rice during Magnaporthe oryzae Infection

    Directory of Open Access Journals (Sweden)

    Yiming Wang

    2014-12-01

    Full Text Available Rice blast disease caused by Magnaporthe oryzae is one of the most serious diseases of cultivated rice (Oryza sativa L. in most rice-growing regions of the world. In order to investigate early response genes in rice, we utilized the transcriptome analysis approach using a 300 K tilling microarray to rice leaves infected with compatible and incompatible M. oryzae strains. Prior to the microarray experiment, total RNA was validated by measuring the differential expression of rice defense-related marker genes (chitinase 2, barwin, PBZ1, and PR-10 by RT-PCR, and phytoalexins (sakuranetin and momilactone A with HPLC. Microarray analysis revealed that 231 genes were up-regulated (>2 fold change, p < 0.05 in the incompatible interaction compared to the compatible one. Highly expressed genes were functionally characterized into metabolic processes and oxidation-reduction categories. The oxidative stress response was induced in both early and later infection stages. Biotic stress overview from MapMan analysis revealed that the phytohormone ethylene as well as signaling molecules jasmonic acid and salicylic acid is important for defense gene regulation. WRKY and Myb transcription factors were also involved in signal transduction processes. Additionally, receptor-like kinases were more likely associated with the defense response, and their expression patterns were validated by RT-PCR. Our results suggest that candidate genes, including receptor-like protein kinases, may play a key role in disease resistance against M. oryzae attack.

  10. Characterization of the early pulmonary inflammatory response associated with PTFE fume exposure

    Science.gov (United States)

    Johnston, C. J.; Finkelstein, J. N.; Gelein, R.; Baggs, R.; Oberdorster, G.; Clarkson, T. W. (Principal Investigator)

    1996-01-01

    Heating of polytetrafluoroethylene (PTFE) has been described to release fumes containing ultrafine particles (approximately 18 nm diam). These fumes can be highly toxic in the respiratory tract inducing extensive pulmonary edema with hemorrhagic inflammation. Fischer-344 rats were exposed to PTFE fumes generated by temperatures ranging from 450 to 460 degrees C for 15 min at an exposure concentration of 5 x 10(5) particles/cm3, equivalent to approximately 50 micrograms/m3. Responses were examined 4 hr post-treatment when these rats demonstrated 60-85% neutrophils (PMNs) in their lung lavage. Increases in abundance for messages encoding the antioxidants manganese superoxide dismutase and metallothionein (MT) increased 15- and 40-fold, respectively. For messages encoding the pro- and anti-inflammatory cytokines: inducible nitric oxide synthase, interleukin 1 alpha, 1 beta, and 6 (IL-1 alpha, IL-1 beta, and IL-6), macrophage inflammatory protein-2, and tumor necrosis factor-alpha (TNF alpha) increases of 5-, 5-, 10-, 40-, 40-, and 15-fold were present. Vascular endothelial growth factor, which may play a role in the integrity of the endothelial barrier, was decreased to 20% of controls. In situ sections were hybridized with 33P cRNA probes encoding IL-6, MT, surfactant protein C, and TNF alpha. Increased mRNA abundance for MT and IL-6 was expressed around all airways and interstitial regions with MT and IL-6 demonstrating similar spatial distribution. Large numbers of activated PMNs expressed IL-6, MT, and TNF alpha. Additionally, pulmonary macrophages and epithelial cells were actively involved. These observations support the notion that PTFE fumes containing ultrafine particles initiate a severe inflammatory response at low inhaled particle mass concentrations, which is suggestive of an oxidative injury. Furthermore, PMNs may actively regulate the inflammatory process through cytokine and antioxidant expression.

  11. Early α-fetoprotein response predicts survival in patients with advanced hepatocellular carcinoma treated with sorafenib

    Directory of Open Access Journals (Sweden)

    Lee SH

    2015-04-01

    in AFP responders than in non-responders (72.1% vs 47.0%, respectively; P=0.007. In a sub-group with SD, OS (median 12.7 vs 5.8 months, respectively and PFS (median 9.1 vs 3.7 months, respectively were significantly longer in AFP responders than in non-responders (all P<0.05. Conclusion: Early AFP response may be useful for predicting survival in patients with advanced HCC treated with sorafenib. Keywords: α-fetoprotein, hepatocellular carcinoma, response, prognosis, treatment outcome, sorafenib

  12. [Dose-response relationship of ropivacaine for epidural block in early herpes zoster guided by CT].

    Science.gov (United States)

    Xie, K Y; Ma, J B; Xu, Q; Huang, B; Yao, M; Ni, H D; Deng, J J; Chen, G D

    2017-12-26

    Objective: To determine the dose-response relationship of ropivacaine for epidural block in early herpes zoster by CT guided. Methods: From January 2015 to February 2017, according to the principle of completely random digital table, 80 patients with early herpes zoster who were prepared for epidural block were divided into 4 groups(each group 20 patients): in group A the concentration of ropivacaine was 0.08%, in group B was 0.10%, in group C was 0.12% and in group D was 0.14%.Under CT guidance, epidural puncture was performed in the relevant section, mixing liquid 5.0 ml (with 10% iodohydrin)were injected into epidural gap.CT scan showed that the mixing liquid covered the relevant spinal nerve segmental.The numeric rating scale(NRS) values before treatment and at 30 minutes, the incidence of adverse reactions were recorded, and the treatment were evaluated. The response to ropivacaine for epidural block in early herpes zoster was defined as positive when the NRS values was less than or equal to one.The ED(50), ED(95) and 95% confidence interval ( CI ) of ropivacaine for epidural block in early herpes zoster guided by CT were calculated by probit analysis. Results: The NRS values before treatment were 5.00(4.00, 6.00), 5.00(4.25, 6.00), 5.50(5.00, 6.00) and 5.00(4.00, 6.00), the difference was no significant( Z =2.576, P =0.462). The NRS values at 30 minutes decreased and the effective rate of the treatment increased(χ(2)=8.371, P =0.004), following ropivacaine dose gradient increasing, they were 1.50(1.00, 2.00), 1.00(1.00, 2.00), 0.50(0.00, 1.00) and 0.00(0.00, 1.00), the difference was statistically significant ( Z =17.421, P =0.001). There was one case in group C and four cases in group D were hypoesthesia, others were no significant adverse reactions occurred. The ED(50) and ED(95) (95% CI ) of ropivacaine for epidural block in early herpes zoster guided by CT were 0.078%(0.015%-0.095%)and 0.157%(0.133%-0.271%), respectively. Conclusion: Ropivacaine for

  13. A gene expression profile indicative of early stage HER2 targeted therapy response.

    Science.gov (United States)

    O'Neill, Fiona; Madden, Stephen F; Clynes, Martin; Crown, John; Doolan, Padraig; Aherne, Sinéad T; O'Connor, Robert

    2013-07-01

    Efficacious application of HER2-targetting agents requires the identification of novel predictive biomarkers. Lapatinib, afatinib and neratinib are tyrosine kinase inhibitors (TKIs) of HER2 and EGFR growth factor receptors. A panel of breast cancer cell lines was treated with these agents, trastuzumab, gefitinib and cytotoxic therapies and the expression pattern of a specific panel of genes using RT-PCR was investigated as a potential marker of early drug response to HER2-targeting therapies. Treatment of HER2 TKI-sensitive SKBR3 and BT474 cell lines with lapatinib, afatinib and neratinib induced an increase in the expression of RB1CC1, ERBB3, FOXO3a and NR3C1. The response directly correlated with the degree of sensitivity. This expression pattern switched from up-regulated to down-regulated in the HER2 expressing, HER2-TKI insensitive cell line MDAMB453. Expression of the CCND1 gene demonstrated an inversely proportional response to drug exposure. A similar expression pattern was observed following the treatment with both neratinib and afatinib. These patterns were retained following exposure to traztuzumab and lapatinib plus capecitabine. In contrast, gefitinib, dasatinib and epirubicin treatment resulted in a completely different expression pattern change. In these HER2-expressing cell line models, lapatinib, neratinib, afatinib and trastuzumab treatment generated a characteristic and specific gene expression response, proportionate to the sensitivity of the cell lines to the HER2 inhibitor.Characterisation of the induced changes in expression levels of these genes may therefore give a valuable, very early predictor of the likely extent and specificity of tumour HER2 inhibitor response in patients, potentially guiding more specific use of these agents.

  14. Bioprinting for vascular and vascularized tissue biofabrication.

    Science.gov (United States)

    Datta, Pallab; Ayan, Bugra; Ozbolat, Ibrahim T

    2017-03-15

    Bioprinting is a promising technology to fabricate design-specific tissue constructs due to its ability to create complex, heterocellular structures with anatomical precision. Bioprinting enables the deposition of various biologics including growth factors, cells, genes, neo-tissues and extra-cellular matrix-like hydrogels. Benefits of bioprinting have started to make a mark in the fields of tissue engineering, regenerative medicine and pharmaceutics. Specifically, in the field of tissue engineering, the creation of vascularized tissue constructs has remained a principal challenge till date. However, given the myriad advantages over other biofabrication methods, it becomes organic to expect that bioprinting can provide a viable solution for the vascularization problem, and facilitate the clinical translation of tissue engineered constructs. This article provides a comprehensive account of bioprinting of vascular and vascularized tissue constructs. The review is structured as introducing the scope of bioprinting in tissue engineering applications, key vascular anatomical features and then a thorough coverage of 3D bioprinting using extrusion-, droplet- and laser-based bioprinting for fabrication of vascular tissue constructs. The review then provides the reader with the use of bioprinting for obtaining thick vascularized tissues using sacrificial bioink materials. Current challenges are discussed, a comparative evaluation of different bioprinting modalities is presented and future prospects are provided to the reader. Biofabrication of living tissues and organs at the clinically-relevant volumes vitally depends on the integration of vascular network. Despite the great progress in traditional biofabrication approaches, building perfusable hierarchical vascular network is a major challenge. Bioprinting is an emerging technology to fabricate design-specific tissue constructs due to its ability to create complex, heterocellular structures with anatomical precision

  15. Proatherogenic pathways leading to vascular calcification

    International Nuclear Information System (INIS)

    Mazzini, Michael J.; Schulze, P. Christian

    2006-01-01

    Cardiovascular disease is the leading cause of morbidity and mortality in the western world and atherosclerosis is the major common underlying disease. The pathogenesis of atherosclerosis involves local vascular injury, inflammation and oxidative stress as well as vascular calcification. Vascular calcification has long been regarded as a degenerative process leading to mineral deposition in the vascular wall characteristic for late stages of atherosclerosis. However, recent studies identified vascular calcification in early stages of atherosclerosis and its occurrence has been linked to clinical events in patients with cardiovascular disease. Its degree correlates with local vascular inflammation and with the overall impact and the progression of atherosclerosis. Over the last decade, diverse and highly regulated molecular signaling cascades controlling vascular calcification have been described. Local and circulating molecules such as osteopontin, osteoprogerin, leptin and matrix Gla protein were identified as critical regulators of vascular calcification. We here review the current knowledge on molecular pathways of vascular calcification and their relevance for the progression of cardiovascular disease

  16. Early establishment of trees at the alpine treeline: idiosyncratic species responses to temperature-moisture interactions.

    Science.gov (United States)

    Loranger, Hannah; Zotz, Gerhard; Bader, Maaike Y

    2016-01-01

    On a global scale, temperature is the main determinant of arctic and alpine treeline position. However on a local scale, treeline form and position vary considerably due to other climatic factors, tree species ecology and life-stage-dependent responses. For treelines to advance poleward or uphill, the first steps are germination and seedling establishment. These earliest life stages may be major bottlenecks for treeline tree populations and will depend differently on climatic conditions than adult trees. We investigated the effect of soil temperature and moisture on germination and early seedling survival in a field experiment in the French Alps near the local treeline (2100 m a.s.l.) using passive temperature manipulations and two watering regimes. Five European treeline tree species were studied: Larix decidua, Picea abies, Pinus cembra, Pinus uncinata and Sorbus aucuparia In addition, we monitored the germination response of three of these species to low temperatures under controlled conditions in growth chambers. The early establishment of these trees at the alpine treeline was limited either by temperature or by moisture, the sensitivity to one factor often depending on the intensity of the other. The results showed that the relative importance of the two factors and the direction of the effects are highly species-specific, while both factors tend to have consistent effects on both germination and early seedling survival within each species. We show that temperature and water availability are both important contributors to establishment patterns of treeline trees and hence to species-specific forms and positions of alpine treelines. The observed idiosyncratic species responses highlight the need for studies including several species and life-stages to create predictive power concerning future treeline dynamics. © The Authors 2016. Published by Oxford University Press on behalf of the Annals of Botany Company.

  17. Protein-energy malnutrition during early gestation in sheep blunts fetal renal vascular and nephron development and compromises adult renal function.

    Science.gov (United States)

    Lloyd, Louise J; Foster, Thomas; Rhodes, Phillip; Rhind, Stewart M; Gardner, David S

    2012-01-15

    A nutritionally poor maternal diet can reduce nephron endowment and pre-empt premature expression of markers for chronic renal disease in the offspring. A mechanistic pathway from variation in maternal diet through altered fetal renal development to compromised adult kidney structure and function with adult-onset obesity has not been described. We show that maternal protein-energy malnutrition in sheep blunts nephrogenic potential in the 0.44 gestation (65 days gestation, term ∼147 days) fetus by increasing apoptosis and decreasing angiogenesis in the nephrogenic zone, effects that were more marked in male fetuses. As adults, the low-protein-exposed sheep had reduced glomerular number and microvascular rarefaction in their kidneys compensated for, respectively, by glomerular hypertrophy and increased angiogenic support. In this study, the long-term mild anatomical deficits in the kidney would have remained asymptomatic in the lean state, but when superimposed on the broad metabolic challenge that obesity represents then microalbuminuria and blunted bilateral renal function revealed a long-term physiological compromise, that is only predicted to worsen with age. In conclusion, maternal protein-energy malnutrition specifically impacts fetal kidney vascular development and prevents full functionality of the adult kidney being achieved; these residual deficits are predicted to significantly increase the expected incidence of chronic kidney disease in prenatally undernourished individuals especially when coupled with a Western obesogenic environment.

  18. Dynamics of nephron-vascular network

    DEFF Research Database (Denmark)

    Postnov, Dmitry; Postnov, D E; Marsh, D J

    2012-01-01

    The paper presents a modeling study of the spatial dynamics of a nephro-vascular network consisting of individual nephrons connected via a tree-like vascular branching structure. We focus on the effects of nonlinear mechanisms that are responsible for the formation of synchronous patterns in order...

  19. Early 24-hour blood pressure response to Roux-en-Y gastric bypass in obese patients

    DEFF Research Database (Denmark)

    Pedersen, Julie S; Borup, Christian; Damgaard, Morten

    2017-01-01

    Recently, it has been proposed, that the blood pressure (BP) lowering effect of gastric bypass surgery not only is explained by the obtained weight loss, but that the anatomical rearrangement of the gut after 'malabsorptive' surgical techniques, such as the laparoscopic Roux-en-Y gastric bypass...... (LRYGB), may affect BP through a change in a putative 'entero-renal' axis. If so one could anticipate a reduction in BP even before a noticeable weight loss was obtained. The purpose of the present study was to investigate the very early BP response to LRYGB surgery. Ten severely obese hypertensive (mean...

  20. Early Cutaneous Leishmaniasis Patients Infected With Leishmania braziliensis Express Increased Inflammatory Responses After Antimony Therapy.

    Science.gov (United States)

    Costa, Rúbia S; Carvalho, Lucas P; Campos, Taís M; Magalhães, Andréa S; Passos, Sara T; Schriefer, Albert; Silva, Juliana A; Lago, Ednaldo; Paixão, Camilla S; Machado, Paulo; Scott, Phillip; Carvalho, Edgar M

    2018-02-14

    Early cutaneous leishmaniasis (ECL) is characterized by a nonulcerated papular lesion and illness duration less than 30 days. Approximately 4 weeks later, the cutaneous leishmaniasis (CL) ulcers appear. We were surprised to find that failure after antimony therapy (Sb5) is higher in ECL than CL. We hypothesize that the inflammatory response in ECL patients may increase during Sb5 therapy, which leads to treatment failure. A cohort of 44 ECL patients infected by Leishmania braziliensis was established to evaluate the response to Sb5 and to compare immunologic responses in ECL patients with CL and healthy subjects. A hierarchical clustering based on cytokine levels showed a weak positive correlation between proinflammatory cytokine levels and those patients that failed Sb5 treatment. Although Sb5 therapy decreased interferon-γ and tumor necrosis factor levels in CL patients, we were surprised to find that an increase in these cytokines was observed in ECL patients. Moreover, interleukin (IL)-10 was less able to down-modulate immune responses in ECL. The enhanced production of proinflammatory cytokines, due in part to the decreased ability of IL-10 to down-modulate immune response during therapy in ECL, promotes the development and persistence of leishmania ulcer despite antimony therapy. © The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  1. A nationwide web-based automated system for early outbreak detection and rapid response in China

    Directory of Open Access Journals (Sweden)

    Yilan Liao

    2011-03-01

    Full Text Available Timely reporting, effective analyses and rapid distribution of surveillance data can assist in detecting the aberration of disease occurrence and further facilitate a timely response. In China, a new nationwide web-based automated system for outbreak detection and rapid response was developed in 2008. The China Infectious Disease Automated-alert and Response System (CIDARS was developed by the Chinese Center for Disease Control and Prevention based on the surveillance data from the existing electronic National Notifiable Infectious Diseases Reporting Information System (NIDRIS started in 2004. NIDRIS greatly improved the timeliness and completeness of data reporting with real time reporting information via the Internet. CIDARS further facilitates the data analysis, aberration detection, signal dissemination, signal response and information communication needed by public health departments across the country. In CIDARS, three aberration detection methods are used to detect the unusual occurrence of 28 notifiable infectious diseases at the county level and to transmit that information either in real-time or on a daily basis. The Internet, computers and mobile phones are used to accomplish rapid signal generation and dissemination, timely reporting and reviewing of the signal response results. CIDARS has been used nationwide since 2008; all Centers for Disease Control and Prevention (CDC in China at the county, prefecture, provincial and national levels are involved in the system. It assists with early outbreak detection at the local level and prompts reporting of unusual disease occurrences or potential outbreaks to CDCs throughout the country.

  2. Active nuclear transcriptome analysis reveals inflammasome-dependent mechanism for early neutrophil response to Mycobacterium marinum.

    Science.gov (United States)

    Kenyon, Amy; Gavriouchkina, Daria; Zorman, Jernej; Napolitani, Giorgio; Cerundolo, Vincenzo; Sauka-Spengler, Tatjana

    2017-07-26

    The mechanisms governing neutrophil response to Mycobacterium tuberculosis remain poorly understood. In this study we utilise biotagging, a novel genome-wide profiling approach based on cell type-specific in vivo biotinylation in zebrafish to analyse the initial response of neutrophils to Mycobacterium marinum, a close genetic relative of M. tuberculosis used to model tuberculosis. Differential expression analysis following nuclear RNA-seq of neutrophil active transcriptomes reveals a significant upregulation in both damage-sensing and effector components of the inflammasome, including caspase b, NLRC3 ortholog (wu: fb15h11) and il1β. Crispr/Cas9-mediated knockout of caspase b, which acts by proteolytic processing of il1β, results in increased bacterial burden and less infiltration of macrophages to sites of mycobacterial infection, thus impairing granuloma development. We also show that a number of immediate early response genes (IEGs) are responsible for orchestrating the initial neutrophil response to mycobacterial infection. Further perturbation of the IEGs exposes egr3 as a key transcriptional regulator controlling il1β transcription.

  3. Repeated allergen exposure reduce early phase airway response and leukotriene release despite upregulation of 5-lipoxygenase pathways

    Directory of Open Access Journals (Sweden)

    Cui Zhi-Hua

    2012-03-01

    Full Text Available Abstract Background Allergen induced early phase airway response and airway plasma exudation are predominantly mediated by inflammatory mast cell mediators including histamine, cysteinyl leukotrienes (cysLTs and thromboxane A2 (TXA2. The aim of the present study was to evaluate whether repeated allergen exposure affects early phase airway response to allergen challenge. Methods A trimellitic anhydride (TMA sensitized guinea pig model was used to investigate the effects of low dose repeated allergen exposure on cholinergic airway responsiveness, early phase airway response and plasma exudation, as well as local airway production of mast cell derived cysteinyl leukotrienes and thromboxane B2 (TXB2 after allergen challenge. Results Repeated low dose allergen exposure increased cholinergic airway responsiveness. In contrast, early phase airway response and plasma exudation in response to a high-dose allergen challenge were strongly attenuated after repeated low dose allergen exposure. Inhibition of the airway response was unspecific to exposed allergen and independent of histamine receptor blocking. Furthermore, a significant reduction of cysteinyl leukotrienes and TXB2 was found in the airways of animals repeatedly exposed to a low dose allergen. However, in vitro stimulation of airway tissue from animals repeatedly exposed to a low dose allergen with arachidonic acid and calcium ionophore (A23187 induced production of cysteinyl leukotrienes and TXB2, suggesting enhanced activity of 5-lipoxygenase and cyclooxygenase pathways. Conclusions The inhibition of the early phase airway response, cysteinyl leukotriene and TXB2 production after repeated allergen exposure may result from unresponsive effector cells.

  4. A New Computational Model for Neuro-Glio-Vascular Coupling: Astrocyte Activation Can Explain Cerebral Blood Flow Nonlinear Response to Interictal Events.

    Directory of Open Access Journals (Sweden)

    Solenna Blanchard

    Full Text Available Developing a clear understanding of the relationship between cerebral blood flow (CBF response and neuronal activity is of significant importance because CBF increase is essential to the health of neurons, for instance through oxygen supply. This relationship can be investigated by analyzing multimodal (fMRI, PET, laser Doppler… recordings. However, the important number of intermediate (non-observable variables involved in the underlying neurovascular coupling makes the discovery of mechanisms all the more difficult from the sole multimodal data. We present a new computational model developed at the population scale (voxel with physiologically relevant but simple equations to facilitate the interpretation of regional multimodal recordings. This model links neuronal activity to regional CBF dynamics through neuro-glio-vascular coupling. This coupling involves a population of glial cells called astrocytes via their role in neurotransmitter (glutamate and GABA recycling and their impact on neighboring vessels. In epilepsy, neuronal networks generate epileptiform discharges, leading to variations in astrocytic and CBF dynamics. In this study, we took advantage of these large variations in neuronal activity magnitude to test the capacity of our model to reproduce experimental data. We compared simulations from our model with isolated epileptiform events, which were obtained in vivo by simultaneous local field potential and laser Doppler recordings in rats after local bicuculline injection. We showed a predominant neuronal contribution for low level discharges and a significant astrocytic contribution for higher level discharges. Besides, neuronal contribution to CBF was linear while astrocytic contribution was nonlinear. Results thus indicate that the relationship between neuronal activity and CBF magnitudes can be nonlinear for isolated events and that this nonlinearity is due to astrocytic activity, highlighting the importance of astrocytes in

  5. Development of an Infection-Responsive Fluorescent Sensor for the Early Detection of Urinary Catheter Blockage.

    Science.gov (United States)

    Milo, Scarlet; Acosta, Florianne B; Hathaway, Hollie J; Wallace, Laura A; Thet, Naing T; Jenkins, A Toby A

    2018-03-23

    Formation of crystalline biofilms following infection by Proteus mirabilis can lead to encrustation and blockage of long-term indwelling catheters, with serious clinical consequences. We describe a simple sensor, placed within the catheter drainage bag, to alert of impending blockage via a urinary color change. The pH-responsive sensor is a dual-layered polymeric "lozenge", able to release the self-quenching dye 5(6)-carboxyfluorescein in response to the alkaline urine generated by the expression of bacterial urease. Sensor performance was evaluated within a laboratory model of the catheterized urinary tract, infected with both urease positive and negative bacterial strains under conditions of established infection, achieving an average "early warning" of catheter blockage of 14.5 h. Signaling only occurred following infection with urease positive bacteria. Translation of these sensors into a clinical environment would allow appropriate intervention before the occurrence of catheter blockage, a problem for which there is currently no effective control method.

  6. Characterization of the early local immune response to Ixodes ricinus tick bites in human skin.

    Science.gov (United States)

    Glatz, Martin; Means, Terry; Haas, Josef; Steere, Allen C; Müllegger, Robert R

    2017-03-01

    Little is known about the immunomodulation by tick saliva during a natural tick bite in human skin, the site of the tick-host interaction. We examined the expression of chemokines, cytokines and leucocyte markers on the mRNA levels and histopathologic changes in human skin biopsies of tick bites (n=37) compared to unaffected skin (n=9). Early tick-bite skin lesions (skin. With longer tick attachment (>24 hours), the numbers of innate immune cells and mediators (not significantly) declined, whereas the numbers of lymphocytes (not significantly) increased. Natural tick bites by Ixodes ricinus ticks initially elicit a strong local innate immune response in human skin. Beyond 24 hours of tick attachment, this response usually becomes less, perhaps because of immunomodulation by tick saliva. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Early developmental responses to seedling environment modulate later plasticity to light spectral quality.

    Directory of Open Access Journals (Sweden)

    Eric J B von Wettberg

    Full Text Available Correlations between developmentally plastic traits may constrain the joint evolution of traits. In plants, both seedling de-etiolation and shade avoidance elongation responses to crowding and foliage shade are mediated by partially overlapping developmental pathways, suggesting the possibility of pleiotropic constraints. To test for such constraints, we exposed inbred lines of Impatiens capensis to factorial combinations of leaf litter (which affects de-etiolation and simulated foliage shade (which affects phytochrome-mediated shade avoidance. Increased elongation of hypocotyls caused by leaf litter phenotypically enhanced subsequent elongation of the first internode in response to low red:far red (R:FR. Trait expression was correlated across litter and shade conditions, suggesting that phenotypic effects of early plasticity on later plasticity may affect variation in elongation traits available to selection in different light environments.

  8. Early change in coping strategies in responsive treatments for borderline personality disorder: A mediation analysis.

    Science.gov (United States)

    Kramer, Ueli; Keller, Sabine; Caspar, Franz; de Roten, Yves; Despland, Jean-Nicolas; Kolly, Stéphane

    2017-05-01

    Difficulty in emotion regulation is a hallmark feature of patients with borderline personality disorder (BPD). Therefore, change in the frequency of certain patients' coping strategies-aiming at emotion regulation-are among the most promising mechanisms of change in treatments for BPD. In parallel, it was highlighted that therapist responsiveness significantly contributed to outcome across treatment approaches (Stiles, 2009). Based on a randomized controlled trial (Kramer et al., 2014), the present process-outcome mediation analysis aims at examining the patient's early change in frequency of coping strategies-in particular the decrease in behavioral forms of coping-as potential mechanism of change in responsive treatments for BPD. A total of 57 patients with BPD were included in the present analysis, out of whom 27 were randomly assigned to a 10-session psychiatric treatment and 30 to a 10-session psychiatric treatment augmented with the responsive intervention of the motive-oriented therapeutic relationship (Caspar, 2007). The 1st, 5th, and 9th session of each therapy were transcribed and analyzed using the Coping Action Pattern Rating Scale (Perry et al., 2005; 171 sessions analyzed in total), a validated observer-rated method for assessing coping strategies in the therapy process. Psychological distress was assessed using the OQ-45 at intake, after Session 5, and after Session 10. The results confirmed a responsiveness effect associated with the motive-oriented therapeutic relationship and showed a significant decrease in frequency of behavioral forms of coping, F(1, 54) = 3.09, p = .05, d = .56, which was not different between the 2 conditions. In addition, we demonstrated that the early decrease in behavioral forms of coping between Sessions 1 and 5 partially mediated the link between the group assignment and the change in psychological distress between Sessions 5 and 10. These results shed light on the centrality of therapist responsiveness in treatments for

  9. Discrimination of timbre in early auditory responses of the human brain.

    Directory of Open Access Journals (Sweden)

    Jaeho Seol

    Full Text Available BACKGROUND: The issue of how differences in timbre are represented in the neural response still has not been well addressed, particularly with regard to the relevant brain mechanisms. Here we employ phasing and clipping of tones to produce auditory stimuli differing to describe the multidimensional nature of timbre. We investigated the auditory response and sensory gating as well, using by magnetoencephalography (MEG. METHODOLOGY/PRINCIPAL FINDINGS: Thirty-five healthy subjects without hearing deficit participated in the experiments. Two different or same tones in timbre were presented through conditioning (S1-testing (S2 paradigm as a pair with an interval of 500 ms. As a result, the magnitudes of auditory M50 and M100 responses were different with timbre in both hemispheres. This result might support that timbre, at least by phasing and clipping, is discriminated in the auditory early processing. The second response in a pair affected by S1 in the consecutive stimuli occurred in M100 of the left hemisphere, whereas both M50 and M100 responses to S2 only in the right hemisphere reflected whether two stimuli in a pair were the same or not. Both M50 and M100 magnitudes were different with the presenting order (S1 vs. S2 for both same and different conditions in the both hemispheres. CONCLUSIONS/SIGNIFICANCES: Our results demonstrate that the auditory response depends on timbre characteristics. Moreover, it was revealed that the auditory sensory gating is determined not by the stimulus that directly evokes the response, but rather by whether or not the two stimuli are identical in timbre.

  10. Response of Soybean to Early-Season Planting Dates along the Upper Texas Gulf Coast

    Directory of Open Access Journals (Sweden)

    W. James Grichar

    2014-01-01

    Full Text Available Soybeans (Glycine max L. can be planted along the upper Texas Gulf Coast from mid-March through May to take advantage of early season rains and to complete harvest before hurricane season and fall rains become a problem. However, in the Calhoun County area (28.5° north latitude, these planting dates have resulted in below average yields and reasons for these yield reductions are not clear. To determine if earlier planting dates could be an option to eliminate the low yields, field studies were conducted from 2005 through 2010 in Calhoun County, Texas, to determine soybean cultivar response to planting dates which ranged from mid-February through the last of April. Typically, soil temperatures in this area are above 18°C in mid-February and depending on weather patterns may not fall much lower during any time in the early portion of the growing season. The greatest yield was obtained with the mid-February and mid-March planting dates compared with early- or late-April planting dates. Typically, as planting date was delayed, the interval between planting and harvest decreased.

  11. Non-invasive vascular imaging: assessing tumour vascularity

    International Nuclear Information System (INIS)

    Delorme, S.; Knopp, M.V.

    1998-01-01

    Non-invasive assessment of vascularity is a new diagnostic approach to characterise tumours. Vascular assessment is based on the pathophysiology of tumour angiogenesis and its diagnostic implications for tumour biology, prognosis and therapy response. Two current techniques investigating vascular features in addition to morphology are Doppler ultrasonography and contrast-enhanced MRI. Diagnostic differentiation has been shown to be possible with Doppler, and a high degree of observed vascularity could be linked to an aggressive course of the disease. Dynamic MRI using gadolinium chelates is already used clinically to detect and differentiate tumours. The histological correlation shows that capillary permeability is increased in malignant tumours and is the best criterion for differentiation from benign processes. Permeability and perfusion factors seem to be more diagnostic than overall vessel density. New clinical applications are currently being established for therapy monitoring. Further instrumental developments will bring harmonic imaging in Doppler, and faster imaging techniques, higher spatial resolution and novel pharmacokinetic concepts in MRI. Upcoming contrast agents for both Doppler and MRI will further improve estimation of intratumoural blood volume and vascular permeability. (orig.)

  12. Regulation of radiation-induced apoptosis by early growth response-1 gene in solid tumors

    International Nuclear Information System (INIS)

    Ahmed, M.

    2003-01-01

    Ionizing radiation exposure is associated with activation of certain immediate-early genes that function as transcription factors. These include members of jun or fos and early growth response (EGR) gene families. In particular, the functional role of EGR-1 in radiation-induced signaling is pivotal since the promoter of EGR-1 contains radiation-inducible CArG DNA sequences. The Egr-1 gene belongs to a family of Egr genes that includes EGR-2, EGR-3, EGR-4, EGR-α and the tumor suppressor, Wilms' tumor gene product, WT1. The Egr-1 gene product, EGR-1, is a nuclear protein that contains three zinc fingers of the C 2 H 2 subtype. The EGR-1 GC-rich consensus target sequence, 5'-GCGT/GGGGCG-3' or 5'-TCCT/ACCTCCTCC-3', has been identified in the promoter regions of transcription factors, growth factors, receptors, cell cycle regulators and pro-apoptotic genes. The gene targets mediated by Egr-1 in response to ionizing radiation include TNF-α , p53, Rb and Bax, all these are effectors of apoptosis. Based on these targets, Egr-1 is a pivotal gene that initiates early signal transduction events in response to ionizing radiation leading to either growth arrest or cell death in tumor cells. There are two potential application of Egr-1 gene in therapy of cancer. First, the Egr-1 promoter contains information for appropriate spatial and temporal expression in-vivo that can be regulated by ionizing radiation to control transcription of genes that have pro-apoptotic and suicidal function. Secondly, EGR-1 protein can eliminate 'induced-radiation resistance' by inhibiting the functions of radiation-induced pro-survival genes (NFκB activity and bcl-2 expression) and activate pro-apoptotic genes (such as bax) to confer a significant radio-sensitizing effect. Together, the reported findings from my laboratory demonstrate clearly that EGR-1 is an early central gene that confers radiation sensitivity and its pro-apoptotic functions are synergized by abrogation of induced radiation

  13. Pulmonary Vascular Defects in Congenital Diaphragmatic Hernia : the quest for early factors and intervention : Pulmonale vasculaire defecten in congenitale hernia diafragmatica : de zoektocht naar vroege factoren en interventie

    NARCIS (Netherlands)

    D.S. Mous (Daphne)

    2017-01-01

    markdownabstractCongenital diaphragmatic hernia (CDH) is a severe anomaly characterized by a diaphragmatic defect, lung hypoplasia and pulmonary hypertension. The associated pulmonary abnormalities are responsible for the high morbidity and mortality among patients with this disease. Vasodilator

  14. Distribution of Endogenous NO Regulates Early Gravitropic Response and PIN2 Localization in Arabidopsis Roots

    Directory of Open Access Journals (Sweden)

    Ramiro París

    2018-04-01

    Full Text Available High-resolution and automated image analysis of individual roots demonstrated that endogenous nitric oxide (NO contribute significantly to gravitropism of Arabidopsis roots. Lowering of endogenous NO concentrations strongly reduced and even reversed gravitropism, resulting in upward bending, without affecting root growth rate. Notably, the asymmetric accumulation of NO along the upper and lower sides of roots correlated with a positive gravitropic response. Detection of NO by the specific DAF-FM DA fluorescent probe revealed that NO was higher at the lower side of horizontally-oriented roots returning to initial values 2 h after the onset of gravistimulation. We demonstrate that NO promotes plasma membrane re-localization of PIN2 in epidermal cells, which is required during the early root gravitropic response. The dynamic and asymmetric localization of both auxin and NO is critical to regulate auxin polar transport during gravitropism. Our results collectively suggest that, although auxin and NO crosstalk occurs at different levels of regulation, they converge in the regulation of PIN2 membrane trafficking in gravistimulated roots, supporting the notion that a temporally and spatially coordinated network of signal molecules could participate in the early phases of auxin polar transport during gravitropism.

  15. Ultrasonic RF time series for early assessment of the tumor response to chemotherapy.

    Science.gov (United States)

    Lin, Qingguang; Wang, Jianwei; Li, Qing; Lin, Chunyi; Guo, Zhixing; Zheng, Wei; Yan, Cuiju; Li, Anhua; Zhou, Jianhua

    2018-01-05

    Ultrasound radio-frequency (RF) time series have been shown to carry tissue typing information. To evaluate the potential of RF time series for early prediction of tumor response to chemotherapy, 50MCF-7 breast cancer-bearing nude mice were randomized to receive cisplatin and paclitaxel (treatment group; n = 26) or sterile saline (control group; n = 24). Sequential ultrasound imaging was performed on days 0, 3, 6, and 8 of treatment to simultaneously collect B-mode images and RF data. Six RF time series features, slope, intercept, S1, S2, S3 , and S4 , were extracted during RF data analysis and contrasted with microstructural tumor changes on histopathology. Chemotherapy administration reduced tumor growth relative to control on days 6 and 8. Compared with day 0, intercept, S1 , and S2 were increased while slope was decreased on days 3, 6, and 8 in the treatment group. Compared with the control group, intercept, S1, S2, S3 , and S4 were increased, and slope was decreased, on days 3, 6, and 8 in the treatment group. Tumor cell density decreased significantly in the latter on day 3. We conclude that ultrasonic RF time series analysis provides a simple way to noninvasively assess the early tumor response to chemotherapy.

  16. Abnormal early gamma responses to emotional faces differentiate unipolar from bipolar disorder patients.

    Science.gov (United States)

    Liu, T Y; Chen, Y S; Su, T P; Hsieh, J C; Chen, L F

    2014-01-01

    This study investigates the cortical abnormalities of early emotion perception in patients with major depressive disorder (MDD) and bipolar disorder (BD) using gamma oscillations. Twenty-three MDD patients, twenty-five BD patients, and twenty-four normal controls were enrolled and their event-related magnetoencephalographic responses were recorded during implicit emotional tasks. Our results demonstrated abnormal gamma activity within 100 ms in the emotion-related regions (amygdala, orbitofrontal (OFC) cortex, anterior insula (AI), and superior temporal pole) in the MDD patients, suggesting that these patients may have dysfunctions or negativity biases in perceptual binding of emotional features at very early stage. Decreased left superior medial frontal cortex (smFC) responses to happy faces in the MDD patients were correlated with their serious level of depression symptoms, indicating that decreased smFC activity perhaps underlies irregular positive emotion processing in depressed patients. In the BD patients, we showed abnormal activation in visual regions (inferior/middle occipital and middle temporal cortices) which responded to emotional faces within 100 ms, supporting that the BD patients may hyperactively respond to emotional features in perceptual binding. The discriminant function of gamma activation in the left smFC, right medial OFC, right AI/inferior OFC, and the right precentral cortex accurately classified 89.6% of patients as unipolar/bipolar disorders.

  17. Radiofrequency ablation of liver cancer: early evaluation of therapeutic response with contrast-enhanced ultrasonography

    International Nuclear Information System (INIS)

    Choi, Dong Gil; Lim, Hyo K.; Lee, Won Jae; Kim, Seung Hoon; Kim, Min Ju; Kim, Seung Kwon; Jang, Kyung Mi; Lee, Ji Yeon; Lim, Jae Hoon

    2004-01-01

    The early assessment of the therapeutic response after percutaneous radiofrequency (RF) ablation is important, in order to correctly decide whether further treatment is necessary. The residual unablated tumor is usually depicted on contrast-enhanced multiphase helical computed tomography (CT) as a focal enhancing structure during the arterial and portal venous phases. Contrast-enhanced color Doppler and power Doppler ultrasonography (US) have also been used to detect residual tumors. Contrast-enhanced gray-scale US, using a harmonic technology which has recently been introduced, allows for the detection of residual tumors after ablation, without any of the blooming or motion artifacts usually seen on contrast-enhanced color or power Doppler US. Based on our experience and reports in the literature, we consider that contrast-enhanced gray-scale harmonic US constitutes a reliable alternative to contrast-enhanced multiphase CT for the early evaluation of the therapeutic response to RF ablation for liver cancer. This technique was also useful in targeting any residual unablated tumors encountered during additional ablation

  18. The impact of early repeated pain experiences on stress responsiveness and emotionality at maturity in rats.

    Science.gov (United States)

    Page, Gayle G; Blakely, Wendy P; Kim, Miyong

    2005-01-01

    The intensive care necessary for premature newborns is characterized by multiple procedures, many of which are painful. Given emerging evidence that such early pain during this time of high brain plasticity may affect long-term neurodevelopmental and social-emotional functioning, this study explored the impact of early repeated pain on emotionality and stress responsivity at maturity. From birth through postnatal day 7, Fischer 344 pups underwent either paw needle prick every day versus every other day or daily paw touch, or were left unperturbed. Each paw received the designated perturbation once per day. At maturity, some animals underwent emotionality testing: either a 4-day series of open field exposures or a single elevated plus-maze (EPM) exposure. The paw prick groups exhibited less open field habituation and occupied the EPM open arms more. Two weeks later, all animals were either subjected to forced swim or not. At 1h post-swim, animals underwent either blood withdrawal for plasma corticosterone (CS) levels and ex vivo natural killer cell activity (NKCA) or were injected intravenously with radiolabeled NK-sensitive syngeneic MADB106 tumor cells and assessed for lung tumor retention. Sex was a major factor in the manifestation of perturbation-related differences in the biologic outcomes. Whereas postnatal pain differentially affected baseline tumor retention between males and females, only males exhibited perturbation-related differences in swim stress-induced increases in tumor retention and CS. Finally, male-female differences were evident in CS, NKCA, and tumor responses to swim stress. These findings suggest that early pain affects neurodevelopmental function in the mature organism; however, these relationships are complicated by sex differences, the postnatal pain schedule, and the outcome measured.

  19. Early-life risperidone enhances locomotor responses to amphetamine during adulthood.

    Science.gov (United States)

    Lee Stubbeman, Bobbie; Brown, Clifford J; Yates, Justin R; Bardgett, Mark E

    2017-10-05

    Antipsychotic drug prescriptions for pediatric populations have increased over the past 20 years, particularly the use of atypical antipsychotic drugs such as risperidone. Most antipsychotic drugs target forebrain dopamine systems, and early-life antipsychotic drug exposure could conceivably reset forebrain neurotransmitter function in a permanent manner that persists into adulthood. This study determined whether chronic risperidone administration during development modified locomotor responses to the dopamine/norepinephrine agonist, D-amphetamine, in adult rats. Thirty-five male Long-Evans rats received an injection of one of four doses of risperidone (vehicle, .3, 1.0, 3.0mg/kg) each day from postnatal day 14 through 42. Locomotor activity was measured for 1h on postnatal days 46 and 47, and then for 24h once a week over the next two weeks. Beginning on postnatal day 75, rats received one of four doses of amphetamine (saline, .3, 1.0, 3.0mg/kg) once a week for four weeks. Locomotor activity was measured for 27h after amphetamine injection. Rats administered risperidone early in life demonstrated increased activity during the 1 and 24h test sessions conducted prior to postnatal day 75. Taking into account baseline group differences, these same rats exhibited significantly more locomotor activity in response to the moderate dose of amphetamine relative to controls. These results suggest that early-life treatment with atypical antipsychotic drugs, like risperidone, permanently alters forebrain catecholamine function and increases sensitivity to drugs that target such function. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Fish oil supplementation in early infancy modulates developing infant immune responses.

    Science.gov (United States)

    D'Vaz, N; Meldrum, S J; Dunstan, J A; Lee-Pullen, T F; Metcalfe, J; Holt, B J; Serralha, M; Tulic, M K; Mori, T A; Prescott, S L

    2012-08-01

    Maternal fish oil supplementation during pregnancy has been associated with altered infant immune responses and a reduced risk of infant sensitization and eczema. To examine the effect of early postnatal fish oil supplementation on infant cellular immune function at 6 months of age in the context of allergic disease. In a double-blind randomized controlled trial (ACTRN12606000281594), 420 infants of high atopic risk received fish oil [containing 280 mg docosahexaenoic acid (DHA) and 110 mg eicosapentanoic acid (EPA)] or control oil daily from birth to 6 months. One hundred and twenty infants had blood collected at 6 months of age. Fatty acid levels, induced cytokine responses, T cell subsets and monocyte HLA-DR expression were assessed at 6 months of age. Infant allergies were assessed at 6 and 12 months of age. DHA and EPA levels were significantly higher in the fish oil group and erythrocyte arachidonic acid (AA) levels were lower (all P acid (PUFA) levels and associated with lowered allergen-specific Th2 responses and elevated polyclonal Th1 responses. Our results add to existing evidence of n-3 PUFA having immunomodulatory properties that are potentially allergy-protective. © 2012 Blackwell Publishing Ltd.

  1. Predictive value of early viriological response for sustained viriological response in chronic hepatitis c with conventional interferon therapy

    International Nuclear Information System (INIS)

    Awan, A.; Umar, M.; Khaar, H.T.B.; Kulsoom, A.; Minhas, Z.; Ambreen, S.; Habib, N.; Mumtaz, W.; Habib, F.

    2016-01-01

    Background: Hepatitis is a major public health problem in Pakistan due to its strong association with liver failure and hepatocellular carcinoma. In Pakistan, conventional interferon therapy along with Ribavirin is favoured especially in Government funded programs for treatment of Hepatitis C, over the more expensive Pegylated Interferon and Ribavirin combination therapy as recommended by Pakistan society of Gastroenterology and GI endoscopy due to its favourable results observed in genotype 3 which is the dominant genotype of this region. Objective of our study was to assess the viriological responses with standard interferon therapy and to determine the predictive values of early viriological response (EVR) for Sustained Viriological Response (SVR) in chronic hepatitis C patients treated with standard interferon therapy. Methods: A cross sectional study was conducted on patients with chronic hepatitis C having received standard interferon and ribavirin therapy for six months. EVR and SVR were noted for analysis. Positive and negative predictive values of EVR on SVR were calculated. Results: Out of the total sample (N=3075), 1946 (63.3 percentage) patients were tested for EVR. 1386 (71.2 percentage) were positive while 560 (28.8 percentage) were negative while 516 (16.8 percentage) were tested for SVR. Two hundred and eighty-five (55.2 percentage) were positive while 231 (44.8 percentage) were negative. EVR and SVR tested were N=117. Positive predictive value of EVR on SVR was 67.1 percentage and negative predictive value was 65.8 percentage. Statistically significant association between EVR and SVR was determined with Chi square statistic of 11.8 (p-value <0.0001). Conclusion: EVR is a good predictor of response of patients to standard interferon and ribavirin therapy. In the absence of an EVR, it seems imperative to stop further treatment. Virilogical responses with conventional interferon therapy are comparable to those of pegylated interferon therapy so

  2. [The age-related macular degeneration as a vascular disease/part of systemic vasculopathy: contributions to its pathogenesis].

    Science.gov (United States)

    Fischer, Tamás

    2015-03-01

    The wall of blood vessels including those in choroids may be harmed by several repeated and/or prolonged mechanical, physical, chemical, microbiological, immunologic, and genetic impacts (risk factors), which may trigger a protracted response, the so-called host defense response. As a consequence, pathological changes resulting in vascular injury (e. g. atherosclerosis, age-related macular degeneration) may be evolved. Risk factors can also act directly on the endothelium through an increased production of reactive oxygen species promoting an endothelial activation, which leads to endothelial dysfunction, the onset of vascular disease. Thus, endothelial dysfunction is a link between the harmful stimulus and vascular injury; any kind of harmful stimuli may trigger the defensive chain that results in inflammation that may lead to vascular injury. It has been shown that even early age-related macular degeneration is associated with the presence of diffuse arterial disease and patients with early age-related macular degeneration demonstrate signs of systemic and retinal vascular alterations. Chronic inflammation, a feature of AMD, is tightly linked to diseases associated with ED: AMD is accompanied by a general inflammatory response, in the form of complement system activation, similar to that observed in degenerative vascular diseases such as atherosclerosis. All these facts indicate that age-related macular degeneration may be a vascular disease (or part of a systemic vasculopathy). This recognition could have therapeutic implications because restoration of endothelial dysfunction may prevent the development or improve vascular disease resulting in prevention or improvement of age-related macular degeneration as well.

  3. Factors associated with early response to olanzapine and clinical and functional outcomes of early responders treated for schizophrenia in the People’s Republic of China

    Directory of Open Access Journals (Sweden)

    Ye W

    2014-05-01

    Full Text Available Wenyu Ye,1 William Montgomery,2 Zbigniew Kadziola,3 Li Liu,4 Haibo Xue,4 Michael D Stensland,5 Tamas Treuer61Real World Analytics, Eli Lilly and Company, Indianapolis, IN, USA; 2Global Patient Outcomes and Real World Evidence, Eli Lilly Australia Pty Ltd, West Ryde, Australia; 3Real World Analytics Capabilities, Eli Lilly GmbH, Vienna, Austria; 4Lilly Suzhou Pharmaceutical Co, Ltd, Shanghai Branch, People’s Republic of China; 5Agile Outcomes Research, Inc., Rochester, MN, USA; 6Neuroscience Research, Eli Lilly and Company, Budapest, HungaryBackground: The aims of this analysis were to identify factors associated with early response (at 4 weeks to olanzapine treatment and to assess whether early response is associated with better longer-term outcomes for patients with schizophrenia in the People’s Republic of China.Methods: A post hoc analysis of a multi-country, 6-month, prospective, observational study of outpatients with schizophrenia or bipolar mania who initiated or switched to treatment with oral olanzapine was conducted using data from the Chinese schizophrenia subgroup (n=330. Factors associated with early response were identified using a stepwise logistic regression with baseline clinical characteristics, baseline participation in a weight control program, and adherence with antipsychotics during the first 4 weeks of treatment. Mixed models for repeated measures with baseline covariates were used to compare outcomes over time between early responders and early nonresponders to olanzapine.Results: One hundred and thirty patients (40% achieved an early response. Early response was independently predicted by higher baseline Clinical Global Impressions-Severity score (odds ratio [OR] 1.51, 95% confidence interval [CI] 1.15–1.97, fewer years since first diagnosis (OR 0.94, CI 0.90–0.98, a greater number of social activities (OR 1.22, CI 1.05–1.40, participation in a weight control program (OR 1.81, CI 1.04–3.15, and high adherence

  4. Comparative responses to endocrine disrupting compounds in early life stages of Atlantic salmon, Salmo salar.

    Science.gov (United States)

    Duffy, T A; Iwanowicz, L R; McCormick, S D

    2014-07-01

    Atlantic salmon (Salmo salar) are endangered anadromous fish that may be exposed to feminizing endocrine disrupting compounds (EDCs) during early development, potentially altering physiological capacities, survival and fitness. To assess differential life stage sensitivity to common EDCs, we carried out short-term (4 day) exposures using three doses each of 17 α-ethinylestradiol (EE2), 17 β-estradiol (E2), and nonylphenol (NP) on four early life stages; embryos, yolk-sac larvae, feeding fry and 1 year old smolts. Differential response was compared using vitellogenin (Vtg, a precursor egg protein) gene transcription. Smolts were also examined for impacts on plasma Vtg, cortisol, thyroid hormones (T4/T3) and hepatosomatic index (HSI). Compound-related mortality was not observed in any life stage, but Vtg mRNA was elevated in a dose-dependent manner in yolk-sac larvae, fry and smolts but not in embryos. The estrogens EE2 and E2 were consistently stronger inducers of Vtg than NP. Embryos responded significantly to the highest concentration of EE2 only, while older life stages responded to the highest doses of all three compounds, as well as intermediate doses of EE2 and E2. Maximal transcription was greater for fry among the three earliest life stages, suggesting fry may be the most responsive life stage in early development. Smolt plasma Vtg was also significantly increased, and this response was observed at lower doses of each compound than was detected by gene transcription suggesting plasma Vtg is a more sensitive indicator at this life stage. HSI was increased at the highest doses of EE2 and E2, and plasma T3 was decreased at the highest dose of EE2. Our results indicate that all life stages are potentially sensitive to endocrine disruption by estrogenic compounds and that physiological responses were altered over a short window of exposure, indicating the potential for these compounds to impact fish in the wild. Copyright © 2014 Elsevier B.V. All rights

  5. Chronic Hippocampal Expression of Notch Intracellular Domain Induces Vascular Thickening, Reduces Glucose Availability, and Exacerbates Spatial Memory Deficits in a Rat Model of Early Alzheimer.

    Science.gov (United States)

    Galeano, Pablo; Leal, María C; Ferrari, Carina C; Dalmasso, María C; Martino Adami, Pamela V; Farías, María I; Casabona, Juan C; Puntel, Mariana; Do Carmo, Sonia; Smal, Clara; Arán, Martín; Castaño, Eduardo M; Pitossi, Fernando J; Cuello, A Claudio; Morelli, Laura

    2018-03-26

    The specific roles of Notch in progressive adulthood neurodegenerative disorders have begun to be unraveled in recent years. A number of independent studies have shown significant increases of Notch expression in brains from patients at later stages of sporadic Alzheimer's disease (AD). However, the impact of Notch canonical signaling activation in the pathophysiology of AD is still elusive. To further investigate this issue, 2-month-old wild-type (WT) and hemizygous McGill-R-Thy1-APP rats (Tg(+/-)) were injected in CA1 with lentiviral particles (LVP) expressing the transcriptionally active fragment of Notch, known as Notch Intracellular Domain (NICD), (LVP-NICD), or control lentivirus particles (LVP-C). The Tg(+/-) rat model captures presymptomatic aspects of the AD pathology, including intraneuronal amyloid beta (Aβ) accumulation and early cognitive deficits. Seven months after LVP administration, Morris water maze test was performed, and brains isolated for biochemical and histological analysis. Our results showed a learning impairment and a worsening of spatial memory in LVP-NICD- as compared to LVP-C-injected Tg(+/-) rats. In addition, immuno histochemistry, ELISA multiplex, Western blot, RT-qPCR, and 1 H-NMR spectrometry of cerebrospinal fluid (CSF) indicated that chronic expression of NICD promoted hippocampal vessel thickening with accumulation of Aβ in brain microvasculature, alteration of blood-brain barrier (BBB) permeability, and a decrease of CSF glucose levels. These findings suggest that, in the presence of early Aβ pathology, expression of NICD may contribute to the development of microvascular abnormalities, altering glucose transport at the BBB with impact on early decline of spatial learning and memory.

  6. Prior acetaminophen consumption impacts the early adaptive cellular response of human skeletal muscle to resistance exercise.

    Science.gov (United States)

    D'Lugos, Andrew C; Patel, Shivam H; Ormsby, Jordan C; Curtis, Donald P; Fry, Christopher S; Carroll, Chad C; Dickinson, Jared M

    2018-04-01

    Resistance exercise (RE) is a powerful stimulus for skeletal muscle adaptation. Previous data demonstrate that cyclooxygenase (COX)-inhibiting drugs alter the cellular mechanisms regulating the adaptive response of skeletal muscle. The purpose of this study was to determine whether prior consumption of the COX inhibitor acetaminophen (APAP) alters the immediate adaptive cellular response in human skeletal muscle after RE. In a double-blinded, randomized, crossover design, healthy young men ( n = 8, 25 ± 1 yr) performed two trials of unilateral knee extension RE (8 sets, 10 reps, 65% max strength). Subjects ingested either APAP (1,000 mg/6 h) or placebo (PLA) for 24 h before RE (final dose consumed immediately after RE). Muscle biopsies (vastus lateralis) were collected at rest and 1 h and 3 h after exercise. Mammalian target of rapamycin (mTOR) complex 1 signaling was assessed through immunoblot and immunohistochemistry, and mRNA expression of myogenic genes was examined via RT-qPCR. At 1 h p-rpS6 Ser240/244 was increased in both groups but to a greater extent in PLA. At 3 h p-S6K1 Thr389 was elevated only in PLA. Furthermore, localization of mTOR to the lysosome (LAMP2) in myosin heavy chain (MHC) II fibers increased 3 h after exercise only in PLA. mTOR-LAMP2 colocalization in MHC I fibers was greater in PLA vs. APAP 1 h after exercise. Myostatin mRNA expression was reduced 1 h after exercise only in PLA. MYF6 mRNA expression was increased 1 h and 3 h after exercise only in APAP. APAP consumption appears to alter the early adaptive cellular response of skeletal muscle to RE. These findings further highlight the mechanisms through which COX-inhibiting drugs impact the adaptive response of skeletal muscle to exercise. NEW & NOTEWORTHY The extent to which the cellular reaction to acetaminophen impacts the mechanisms regulating the adaptive response of human skeletal muscle to resistance exercise is not well understood. Consumption of acetaminophen before

  7. Ethanol, saccharin, and quinine: early ontogeny of taste responsiveness and intake.

    Science.gov (United States)

    Kozlov, Andrey P; Varlinskaya, Elena I; Spear, Norman E

    2008-02-01

    Rat pups demonstrate high levels of immediate acceptance of ethanol during the first 2 weeks of postnatal life. Given that the taste of ethanol is most likely perceived by infant rats as a combination of sweet and bitter, high intake of ethanol early in ontogeny may be associated with age-related enhanced responsiveness to the sweet component of ethanol taste, as well as with ontogenetic decreases in sensitivity to its bitter component. Therefore, the present study compared responsiveness to ethanol and solutions with bitter (quinine) and sweet (saccharin) taste in terms of intake and palatability across the first 2 weeks of postnatal life. Characteristic patterns of responsiveness to 10% (v/v) ethanol, 0.1% saccharin, 0.2% quinine, and water in terms of taste reactivity and fluid intake were assessed in rat pups tested on postnatal day (P) 4, 9, or 12 using a new technique of on-line monitoring of fluid flow through a two-channel intraoral cannula. Taste reactivity included analysis of ingestive and aversive responses following six intraoral infusions of the test fluids. This taste reactivity probe was followed by the intake test, in which animals were allowed to voluntarily ingest fluids from an intraoral cannula. Pups of all ages showed more appetitive responses to saccharin and ethanol than to water or quinine. No age-related differences were apparent in taste responsiveness to saccharin and ethanol. However, the age-related pattern of ethanol intake drastically differed from that of saccharin. Intake of saccharin increased from P4 to P9 and decreased substantially by P12, whereas intake of ethanol gradually increased from P4 to P12. Intake of ethanol was significantly lower than intake of saccharin on P9, whereas P12 pups took in more ethanol than saccharin. The findings of the present study indicate ontogenetic dissociations between taste reactivity to ethanol and saccharin and intake of these solutions, and suggest that high acceptance of ethanol early in

  8. The relationship between early ego strength and adolescent responses to the threat of nuclear war

    International Nuclear Information System (INIS)

    Andrekus, N.J.

    1989-01-01

    Ego resiliency and ego control, measured when subjects were 3 or 4 years old, were related to expectation of war, concern for the future, and activism in response to the threat of nuclear war, measured when subjects were 18 years old. Data from 92 participants in a longitudinal study of ego and cognitive development conducted by Jeanne and Jack Block at the University of California, Berkeley were used to test hypotheses. Assessments with the California Child Q-set, composited across multiple independent observers, provide measures of ego resiliency and ego control. Adolescent interviews regarding the perception of likelihood of nuclear war, how this affects their future, and their antinuclear and general political activism were scaled and rated. Early ego resiliency and ego under control were hypothesized to account for the variance in adolescent nuclear responses and activism. The only significant longitudinal relationships were in the female sample, where ego under control was found to be a significant predictor of both general political activism (p<.01) and ideas of the future being affected by the nuclear threat (p<.05). Among males, the relationship between early ego resiliency and adolescent antinuclear activism approached significance (p<.10). Adolescent personality was significantly related to several measures of nuclear response. In girls, adolescent ego under control related to perception of likelihood of nuclear war (p<.05) and antinuclear activism (p<.05), and the interaction of ego resiliency and ego under control predicted general political activism (p<.0005). In boys, adolescent ego resiliency correlated with antinuclear activism (p<.05). These findings were discussed in terms of antecedent parenting styles, and conceptual links were drawn between children's ego resiliency and security of attachment, perspective taking, and moral development

  9. Perfusion MDCT enables early detection of therapeutic response to antiangiogenic therapy.

    Science.gov (United States)

    Sabir, Adeel; Schor-Bardach, Rachel; Wilcox, Carol J; Rahmanuddin, Syed; Atkins, Michael B; Kruskal, Jonathan B; Signoretti, Sabina; Raptopoulos, Vassilios D; Goldberg, S Nahum

    2008-07-01

    The objective of our study was to determine whether perfusion CT can be used to detect early changes in therapeutic response to antiangiogenic therapy in an animal tumor model. Twenty-five rats implanted with R3230 mammary adenocarcinoma (diameter, 1.2-2.0 cm) randomly received 7.5 or 30 mg/kg of an antiangiogenic agent, sorafenib, by daily gavage for 4 (n = 4), 9 (n = 9), or 14 (n = 5) days. Seven untreated animals served as a control group. Perfusion MDCT was performed at days 0, 4, 9, and 14 with 0.4 mL of ioversol (350 mg/mL) and included four 5-mm slices covering the entire tumor volume. Changes in tumor growth were determined by volumetric analysis of CT data. Serial changes in tumor volume and blood flow were assessed and correlated with pathology findings. All control tumors grew larger (from 2.0 +/- 0.7 cm(3) at day 0 to 5.9 +/- 1.0 cm(3) at day 14), whereas all treated tumors shrank (from 2.5 +/- 1.1 to 2.1 +/- 1.0 cm(3)), with a statistically significant rate of growth or shrinkage in both groups (p histopathologic viability despite the fact that these tumors were shrinking in size from day 4 onward (day 4, 2.18 +/- 0.8 cm(3); day 9, 1.98 +/- 0.8 cm(3)). Perfusion MDCT can detect focal blood flow changes even when the tumor is shrinking, possibly indicating early reversal of tumor responsiveness to antiangiogenic therapy. Given that changes in tumor volume after antiangiogenic therapy do not necessarily correlate with true treatment response, physiologic imaging of tumor perfusion may be necessary.

  10. The relationship between early ego strength and adolescent responses to the threat of nuclear war

    Energy Technology Data Exchange (ETDEWEB)

    Andrekus, N.J.

    1989-01-01

    Ego resiliency and ego control, measured when subjects were 3 or 4 years old, were related to expectation of war, concern for the future, and activism in response to the threat of nuclear war, measured when subjects were 18 years old. Data from 92 participants in a longitudinal study of ego and cognitive development conducted by Jeanne and Jack Block at the University of California, Berkeley were used to test hypotheses. Assessments with the California Child Q-set, composited across multiple independent observers, provide measures of ego resiliency and ego control. Adolescent interviews regarding the perception of likelihood of nuclear war, how this affects their future, and their antinuclear and general political activism were scaled and rated. Early ego resiliency and ego under control were hypothesized to account for the variance in adolescent nuclear responses and activism. The only significant longitudinal relationships were in the female sample, where ego under control was found to be a significant predictor of both general political activism (p<.01) and ideas of the future being affected by the nuclear threat (p<.05). Among males, the relationship between early ego resiliency and adolescent antinuclear activism approached significance (p<.10). Adolescent personality was significantly related to several measures of nuclear response. In girls, adolescent ego under control related to perception of likelihood of nuclear war (p<.05) and antinuclear activism (p<.05), and the interaction of ego resiliency and ego under control predicted general political activism (p<.0005). In boys, adolescent ego resiliency correlated with antinuclear activism (p<.05). These findings were discussed in terms of antecedent parenting styles, and conceptual links were drawn between children's ego resiliency and security of attachment, perspective taking, and moral development.

  11. Phenological behaviour of early spring flowering trees in Spain in response to recent climate changes

    Science.gov (United States)

    Hidalgo-Galvez, M. D.; García-Mozo, H.; Oteros, J.; Mestre, A.; Botey, R.; Galán, C.

    2018-04-01

    This research reports the phenological trends of four early spring and late winter flowering trees in Spain (south Europe) from a recent period (1986-2012). The studied species were deciduous trees growing in different climatic areas: hazel ( Corylus avellana L.), willow ( Salix alba L.), ash ( Fraxinus angustifolia Vahl.) and white mulberry ( Morus alba L.). We analysed the response to climate and the trends of the following phenophases observed at the field: budburst, leaf unfolding, flowering, fruit ripening, fruit harvesting, leaf colour change and leaf-fall. The study was carried out in 17 sampling sites in the country with the aim of detecting the recent phenological response to the climate of these species, and the possible effect of climate change. We have observed differences in the phenological response to climate depending on each species. Sixty-one percent of studied sites suffered an advance of early spring phenophases, especially budburst on average by -0.67 days and flowering on average by -0.15 days during the studied period, and also in the subsequent fruit ripening and harvesting phases on average by -1.06 days. By contrast, it has been detected that 63% of sampling sites showed a delay in autumn vegetative phases, especially leaf-fall events on average by +1.15 days. The statistic correlation analysis shows in the 55% of the studied localities that phenological advances are the consequence of the increasing trend detected for temperature—being minimum temperature the most influential factor—and in the 52% of them, phenological advances occurred by rainfall variations. In general, leaf unfolding and flowering from these species showed negative correlations in relation to temperature and rainfall, whereas that leaf colour change and leaf-fall presented positive correlations. The results obtained have a great relevance due to the fact that they can be considered as reliable bio-indicators of the impact of the recent climate changes in southern

  12. A Radiation-Induced Hippocampal Vascular Injury Surrogate Marker Predicts Late Neurocognitive Dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Farjam, Reza [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Pramanik, Priyanka; Aryal, Madhava P. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Srinivasan, Ashok [Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Chapman, Christopher H. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Tsien, Christina I. [Department of Radiation Oncology, Washington University in St. Louis, St. Louis, Missouri (United States); Lawrence, Theodore S. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Cao, Yue, E-mail: yuecao@umich.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan (United States)

    2015-11-15

    Purpose: We aimed to develop a hippocampal vascular injury surrogate marker for early prediction of late neurocognitive dysfunction in patients receiving brain radiation therapy (RT). Methods and Materials: Twenty-seven patients (17 males and 10 females, 31-80 years of age) were enrolled in an institutional review board-approved prospective longitudinal study. Patients received diagnoses of low-grade glioma or benign tumor and were treated by (3D) conformal or intensity-modulated RT with a median dose of 54 Gy (50.4-59.4 Gy in 1.8-Gy fractions). Six dynamic-contrast enhanced MRI scans were performed from pre-RT to 18-month post-RT, and quantified for vascular parameters related to blood-brain barrier permeability, K{sup trans}, and the fraction of blood plasma volume, V{sub p}. The temporal changes in the means of hippocampal transfer constant K{sup trans} and V{sub p} after starting RT were modeled by integrating the dose effects with age, sex, hippocampal laterality, and presence of tumor or edema near a hippocampus. Finally, the early vascular dose response in hippocampi was correlated with neurocognitive dysfunction at 6 and 18 months post-RT. Results: The mean K{sup trans} Increased significantly from pre-RT to 1-month post-RT (P<.0004), which significantly depended on sex (P<.0007) and age (P<.00004), with the dose response more pronounced in older females. Also, the vascular dose response in the left hippocampus of females correlated significantly with changes in memory function at 6 (r=−0.95, P<.0006) and 18-months (r=−0.88, P<.02) post-RT. Conclusions: The early hippocampal vascular dose response could be a predictor of late neurocognitive dysfunction. A personalized hippocampus sparing strategy may be considered in the future.

  13. A Radiation-Induced Hippocampal Vascular Injury Surrogate Marker Predicts Late Neurocognitive Dysfunction

    International Nuclear Information System (INIS)

    Farjam, Reza; Pramanik, Priyanka; Aryal, Madhava P.; Srinivasan, Ashok; Chapman, Christopher H.; Tsien, Christina I.; Lawrence, Theodore S.; Cao, Yue

    2015-01-01

    Purpose: We aimed to develop a hippocampal vascular injury surrogate marker for early prediction of late neurocognitive dysfunction in patients receiving brain radiation therapy (RT). Methods and Materials: Twenty-seven patients (17 males and 10 females, 31-80 years of age) were enrolled in an institutional review board-approved prospective longitudinal study. Patients received diagnoses of low-grade glioma or benign tumor and were treated by (3D) conformal or intensity-modulated RT with a median dose of 54 Gy (50.4-59.4 Gy in 1.8-Gy fractions). Six dynamic-contrast enhanced MRI scans were performed from pre-RT to 18-month post-RT, and quantified for vascular parameters related to blood-brain barrier permeability, K"t"r"a"n"s, and the fraction of blood plasma volume, V_p. The temporal changes in the means of hippocampal transfer constant K"t"r"a"n"s and V_p after starting RT were modeled by integrating the dose effects with age, sex, hippocampal laterality, and presence of tumor or edema near a hippocampus. Finally, the early vascular dose response in hippocampi was correlated with neurocognitive dysfunction at 6 and 18 months post-RT. Results: The mean K"t"r"a"n"s Increased significantly from pre-RT to 1-month post-RT (P<.0004), which significantly depended on sex (P<.0007) and age (P<.00004), with the dose response more pronounced in older females. Also, the vascular dose response in the left hippocampus of females correlated significantly with changes in memory function at 6 (r=−0.95, P<.0006) and 18-months (r=−0.88, P<.02) post-RT. Conclusions: The early hippocampal vascular dose response could be a predictor of late neurocognitive dysfunction. A personalized hippocampus sparing strategy may be considered in the future.

  14. Biomarkers of drug-induced vascular injury

    International Nuclear Information System (INIS)

    Brott, D.; Gould, S.; Jones, H.; Schofield, J.; Prior, H.; Valentin, J.P; Bjurstrom, S.; Kenne, K.; Schuppe-Koistinen, I.; Katein, A.; Foster-Brown, L.; Betton, G.; Richardson, R.; Evans, G.; Louden, C.

    2005-01-01

    In pre-clinical safety studies, drug-induced vascular injury is an issue of concern because there are no obvious diagnostic markers for pre-clinical or clinical monitoring and there is an intellectual gap in our understanding of the pathogenesis of this lesion. While vasodilatation and increased shear stress appear to play a role, the exact mechanism(s) of injury to the primary targets, smooth muscle and endothelial cells are unknown. However, evaluation of novel markers for potential clinical monitoring with a mechanistic underpinning would add value in risk assessment and management. This mini review focuses on the progress to identify diagnostic markers of drug-induced vascular injury. Von Willebrand factor (vWF), released upon perturbation of endothelial cells, is transiently increased in plasma prior to morphological evidence of damage in dogs or rats treated with vascular toxicants. Therefore, vWF might be a predictive biomarker of vascular injury. However, vWF is not an appropriate biomarker of lesion progression or severity since levels return to baseline values when there is morphological evidence of injury. A potential mechanistically linked biomarker of vascular injury is caveolin-1. Expression of this protein, localized primarily to smooth muscle and endothelial cells, decreases with the onset of vascular damage. Since vascular injury involves multiple mediators and cell types, evaluation of a panel rather than a single biomarker may be more useful in monitoring early and severe progressive vascular injury

  15. Irregular vascular pattern by contrast-enhanced ultrasonography and high serum Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein level predict poor outcome after successful radiofrequency ablation in patients with early-stage hepatocellular carcinoma.

    Science.gov (United States)

    Takada, Hitomi; Tsuchiya, Kaoru; Yasui, Yutaka; Nakakuki, Natsuko; Tamaki, Nobuharu; Suzuki, Shoko; Nakanishi, Hiroyuki; Itakura, Jun; Takahashi, Yuka; Kurosaki, Masayuki; Asahina, Yasuhiro; Enomoto, Nobuyuki; Izumi, Namiki

    2016-11-01

    Radiofrequency ablation (RFA) is considered the most effective treatment for early-stage hepatocellular carcinoma (HCC) patients unsuitable for resection. However, poor outcome after RFA has occasionally been reported worldwide. To predict such an outcome, we investigated imaging findings using contrast-enhanced ultrasonography (CEUS) with Sonazoid and serum tumor markers before RFA. This study included 176 early-stage HCC patients who had initially achieved successful RFA. Patients were examined using CEUS; their levels of alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and des-gamma-carboxy prothrombin before RFA were measured. Sonazoid provided parenchyma-specific contrast imaging and facilitated tumor vascular architecture imaging through maximum intensity projection (MIP). Kaplan-Meier analysis examined cumulative rates of local tumor progression, intrasubsegmental recurrence, and survival; factors associated with these were determined with Cox proportional hazards analysis. Local tumor progression (n = 15), intrasubsegmental recurrence (n = 46), and death (n = 18) were observed. Irregular pattern in MIP classification and serum AFP-L3 level (>10%) before RFA were identified as independent risk factors for local tumor progression and intrasubsegmental recurrence. These two factors were independently associated with poor survival after RFA (irregular pattern in MIP: hazard ratio, (HR) = 8.26; 95% confidence interval, (CI) = 2.24-30.3; P = 0.002 and AFP-L3 > 10%: HR = 2.94; 95% CI = 1.09-7.94; P = 0.033). Irregular MIP pattern by CEUS and high level of serum AFP-L3 were independent risk factors for poor outcome after successful RFA. The Patients with these findings should be considered as special high-risk group in early-stage HCC. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  16. Impaired Early-Response Inhibition in Overweight Females with and without Binge Eating Disorder.

    Directory of Open Access Journals (Sweden)

    Jennifer Svaldi

    Full Text Available Several studies report increased reward sensitivity towards food in overweight individuals. By contrast, data is inconclusive with respect to response inhibition in overweight individuals without binge eating disorder (BED. Hence, the latter was addressed in the present study in a group of overweight/obese females with and without BED and a normal-weight control group without eating disorders.A group of women with BED (n = 29, a group of overweight women without BED (n = 33 and normal-weight females (n = 30 participated in a pictorial priming paradigm, with food items (relevant primes and office utensils (neutral primes and color blobs (neutral primes as stimuli. Increased response priming effects (i.e. priming with switches between stimulus categories were taken as indicators of deficient behavioral inhibition.Priming effects for neutral primes were moderate and comparable across all groups. However, primes associated with the food task set lead to increased priming effects in both overweight groups. But, effects were comparable for overweight/obese participants with and without BED.Results suggest that early response inhibition in the context of food is impaired in overweight individuals compared to normal-weight individuals.

  17. Characterization of early cortical population response to thalamocortical input in vitro

    Directory of Open Access Journals (Sweden)

    Michael Raymond Heliodor Hill

    2014-01-01

    Full Text Available The in vitro thalamocortical slice preparation of mouse barrel cortex allows for stimulation of the cortex through its natural afferent thalamocortical pathway. This preparation was used here to investigate the first stage of cortical processing in the large postsynaptic dendritic networks as revealed by voltage sensitive dye imaging. We identified the precise location and dimensions of two clearly distinguishable dendritic networks, one in the granular layer IV and one in the infragranular layer V and VI and showed that they have different physiological properties. DiI fluorescent staining further revealed that thalamocortical axons project on to these two networks in the typical barrel like form, not only in the granular but also in the infragranular layer. Finally we investigated the short term dynamics of both the voltage sensitive dye imaging signal and the local field potential in response to a train of eight-pulses at various frequencies in both these layers. We found evidence of differences in the plasticity between the first two response peaks compared to the remaining six peaks as well as differences in short term plasticity between the voltage sensitive dye imaging response and the local field potential. Our findings suggest, that at least early cortical processing takes place in two separate dendritic networks that may stand at the beginning of further parallel computation. The detailed characterization of the parameters of these networks may provide tools for further research into the complex dynamics of large dendritic networks and their role in cortical computation.

  18. [Recurrent vascular access trombosis associated with the prothrombin mutation G20210A in a adult patient in haemodialysis].

    Science.gov (United States)

    Quintana, L F; Coll, E; Monteagudo, I; Collado, S; López-Pedret, J; Cases, A

    2005-01-01

    Vascular access-related complications are a frequent cause of morbidity in haemodialysis patients and generate high costs. We present the case of an adult patient with end-stage renal disease and recurrent vascular access thrombosis associated with the prothrombin mutation G20210A and renal graft intolerance. The clinical expression of this heterozygous gene mutation may have been favoured by inflammatory state, frequent in dialysis patients. In this patient, the inflammatory response associated with the renal graft intolerance would have favored the development of recurrent vascular access thrombosis in a adult heterozygous for prothrombin mutation G20210A. In the case of early dysfunction of haemodialysis vascular access and after ruling out technical problems, it is convenient to carry out a screening for thrombophilia.