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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.

  2. Early genetic responses in rat vascular tissue after simulated diving.

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    Eftedal, Ingrid; Jørgensen, Arve; Røsbjørgen, Ragnhild; Flatberg, Arnar; Brubakk, Alf O

    2012-12-18

    Diving causes a transient reduction of vascular function, but the mechanisms behind this are largely unknown. The aim of this study was therefore to analyze genetic reactions that may be involved in acute changes of vascular function in divers. Rats were exposed to 709 kPa of hyperbaric air (149 kPa Po(2)) for 50 min followed by postdive monitoring of vascular bubble formation and full genome microarray analysis of the aorta from diving rats (n = 8) and unexposed controls (n = 9). Upregulation of 23 genes was observed 1 h after simulated diving. The differential gene expression was characteristic of cellular responses to oxidative stress, with functions of upregulated genes including activation and fine-tuning of stress-responsive transcription, cytokine/cytokine receptor signaling, molecular chaperoning, and coagulation. By qRT-PCR, we verified increased transcription of neuron-derived orphan receptor-1 (Nr4a3), plasminogen activator inhibitor 1 (Serpine1), cytokine TWEAK receptor FN14 (Tnfrsf12a), transcription factor class E basic helix-loop-helix protein 40 (Bhlhe40), and adrenomedullin (Adm). Hypoxia-inducible transcription factor HIF1 subunit HIF1-α was stabilized in the aorta 1 h after diving, and after 4 h there was a fivefold increase in total protein levels of the procoagulant plasminogen activator inhibitor 1 (PAI1) in blood plasma from diving rats. The study did not have sufficient power for individual assessment of effects of hyperoxia and decompression-induced bubbles on postdive gene expression. However, differential gene expression in rats without venous bubbles was similar to that of all the diving rats, indicating that elevated Po(2) instigated the observed genetic reactions.

  3. Stomatal Blue Light Response Is Present in Early Vascular Plants1[OPEN

    Science.gov (United States)

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

    2015-01-01

    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. PMID:26307440

  4. Loss of vascular early response gene reduces edema formation after experimental stroke

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    Liu Fudong

    2012-06-01

    Full Text Available Abstract Vascular Early Response Gene (Verge is an immediate early gene (IEG that is up-regulated in endothelial cells in response to a number of stressors, including ischemic stroke. Endothelial cell lines that stably express Verge show enhanced permeability. Increased Verge expression has also been associated with blood brain barrier breakdown. In this study we investigated the role of Verge in ischemic injury induced by middle cerebral artery occlusion (MCAO in both Verge knockout (KO and wild type (WT mice. Verge KO mice had significantly less cerebral edema formation after MCAO compared to WT mice. However, stroke outcome (infarct size and neurological deficit scores evaluated at either 24 or 72 hours after stroke showed no differences between the two genotypes. Verge deletion leads to decreased edema formation after ischemia; however acute stroke outcomes were unchanged.

  5. Early changes in vascular reactivity in response to 56Fe irradiation in ApoE-/- mice

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    White, C. Roger; Yu, Tao; Gupta, Kiran; Babitz, Stephen K.; Black, Leland L.; Kabarowski, Janusz H.; Kucik, Dennis F.

    2015-03-01

    Epidemiological studies have established that radiation from a number of terrestrial sources increases the risk of atherosclerosis. The accelerated heavy ions in the galacto-cosmic radiation (GCR) that astronauts will encounter on in space, however, interact very differently with tissues than most types of terrestrial radiation, so the health consequences of exposure on deep-space missions are not clear. We demonstrated earlier that 56Fe, an important component of cosmic radiation, accelerates atherosclerotic plaque development. In the present study, we examined an earlier, pro-atherogenic event that might be predictive of later atherosclerotic disease. Decreased endothelium-dependent vasodilation is a prominent manifestation of vascular dysfunction that is thought to predispose humans to the development of structural vascular changes that precede the development of atherosclerotic plaques. To test the effect of heavy-ion radiation on endothelium-dependent vasodilation, we used the same ApoE-/- mouse model in which we previously demonstrated the pro-atherogenic effect of 56Fe on plaque development. Ten week old male ApoE mice (an age at which there is little atherosclerotic plaque in the descending aorta) were exposed to 2.6 Gy 56Fe. The mice were then fed a normal diet and housed under standard conditions. At 4-5 weeks post-irradiation, aortic rings were isolated and endothelial-dependent relaxation was measured. Relaxation in response to acetylcholine was significantly impaired in irradiated mice compared to age-matched, un-irradiated mice. This decrease in vascular reactivity following 56Fe irradiation occurred eight weeks prior to the development of statistically significant exacerbation of aortic plaque formation and may contribute to the formation of later atherosclerotic lesions.

  6. 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.

  7. 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

  8. 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

  9. Early growth response gene-1 decoy oligonucleotides inhibit vascular smooth muscle cell proliferation and neointimal hyperplasia of autogenous vein graft in rabbits.

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    Wang, Xisheng; Mei, Yunqing; Ji, Qiang; Feng, Jing; Cai, Jianzhi; Xie, Shiliang

    2015-07-01

    The excess proliferation of vascular smooth muscle cells (VSMCs) and the development of intimal hyperplasia is a hallmark of vein graft failure. This study aimed to verify that a single intraoperative transfection of early growth response gene-1 (Egr-1) decoy oligonucleotide (ODN) can suppress vein graft proliferation of VSMCs and intimal hyperplasia. In a rabbit model, jugular veins were treated with Egr-1 decoy ODN, scrambled decoy ODN, Fugene6, or were left untreated, then grafted to the carotid artery. The vein graft samples were obtained 48 h, 1, 2 or 3 weeks after surgery. The thickness of the intima and intima/media ratio in the grafts was analysed by haematoxylin-eosin (HE) staining. The expression of the Egr-1 decoy ODN transfected in the vein was analysed using fluorescent microscopy. Egr-1 mRNA was measured using reverse transcription-polymerase chain reaction. The expression of Egr-1 protein was analysed by Western blot and immunohistochemistry. Transfection efficiency of the ODN was confirmed by 4', 6-diamidino-2-phenylindole staining. In the grafts treated with Egr-1 decoy ODN, our study achieved statistically significant inhibition of intimal hyperplasia by ∼58% at 3 weeks. Transfection of Egr-1 decoy ODNs decreased the protein expression of Egr-1 and Egr-1 mRNA. We confirmed that gene therapy using in vivo transfection of an Egr-1 decoy ODN significantly inhibits proliferation of VSMC and intimal hyperplasia of vein grafts in a rabbit model. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  10. Pulmonary vascular response of dogs with heartworm disease.

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    Rawlings, C A

    1978-10-01

    Heartworm diseases in dogs is an infectious disease that produces pulmonary hypertension. Dogs with the early vascular changes of heartworm disease, but without the clinical cardiopulmonary signs and pulmonary hypertension, were studied. Dogs with early heartworm were identified that had an exaggerated hypertensive response to hypoxia and to postaglandin F2alpha as compared to those of normal dogs. The pulmonary hypertensive response of dogs with spontaneous heartworm disease varied widely between individuals.

  11. Early vascular complications after pediatric liver transplantation

    NARCIS (Netherlands)

    Sieders, E; Peeters, PMJG; Ten Vergert, EM; de Jong, KP; Porte, RJ; Zwaveling, JH; Bijleveld, CMA; Slooff, MJH

    Vascular complications have a detrimental effect on the outcome after liver transplantation. Most studies focus exclusively on hepatic artery thrombosis (HAT), The current study analyzed the incidence, consequences, and risk factors for HAT, portal vein thrombosis (PVT), and venous outflow tract

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

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    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.)

  13. 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.

  14. [Early death in vascular surgery: an ongoing prognostic problem].

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    Kazimierczak, Arkadiusz; Sledź, Marcin; Guzicka-Kazimierczak, Renata; Gutowski, Piotr; Cnotliwy, Miłosław

    2010-01-01

    Prediction of complications in surgery is commonly done. There are conflicting reports concerning the usefulness of risk scales (P-POSSUM, APACHE, SAPS, ASA, Goldman, etc.) in vascular surgery. We decided to take a fresh look at preoperative risk factors of early death in the context of the usefulness of some parameters which have not been included in existing risk calculators. The study group consisted of 1270 patients treated at the Department of Vascular Surgery, General Surgery, and Angiology, Pomeranian Medical University in Szczecin, during one year. METHOD This was a prospective non-randomized study. All data recorded at admission and data from P-POSSUM, ASA, Goldman, and ECOG-Zubroda-WHO scales were analyzed. Statistics were done with discriminant, multivariate, and logistic tests. There were 42 early deaths in the group. The following independent risk factors were involved in early death: ASA > 2 (OR = 18.31), persistent atrial fibrillation (OR = 5.75), leukocytosis (OR = 13.31), glomerular filtration rate (GFR) SIRS) (OR = 11.36), emergency admission (OR = 38.62), critical limb ischemia (OR = 4.87), acute limb ischemia (OR = 8,98), abdominal aortic aneurysm (OR = 4.4), and ruptured aortic aneurysm (OR = 10.59). Logistic regression exposed the influence of five factors: ASA III, ASA IV, persistent atrial fibrillation, leukocytosis, GFR surgery need to be "refreshed". Creation of the Polish National Vascular Surgery Register seems to be unavoidable.

  15. Dynamic contrast enhanced ultrasound assessment of the vascular effects of novel therapeutics in early stage trials.

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    Leen, Edward; Averkiou, Michalakis; Arditi, Marcel; Burns, Peter; Bokor, Daniela; Gauthier, Thomas; Kono, Yuko; Lucidarme, Olivier

    2012-07-01

    Imaging is key in the accurate monitoring of response to cancer therapies targeting tumour vascularity to inhibit its growth and dissemination. Dynamic contrast enhanced ultrasound (DCE ultrasound) is a quantitative method with the advantage of being non-invasive, widely available, portable, cost effective, highly sensitive and reproducible using agents that are truly intravascular. Under the auspices of the initiative of the Experimental Cancer Medicine Centre Imaging Network, bringing together experts from the UK, Europe and North America for a 2-day workshop in May 2010, this consensus paper aims to provide guidance on the use of DCE ultrasound in the measurement of tumour vascular support in clinical trials. Key Points • DCE ultrasound can quantify and extract specific blood flow parameters, such as flow velocity, relative vascular volume and relative blood flow rate. • DCE ultrasound can be performed repeatedly and is therefore ideally suited for pharmacokinetic and pharmacodynamic studies evaluating vascular-targeted drugs. • DCE ultrasound provides a reproducible method of assessing the vascular effects of therapy in pre-clinical and early clinical trials, which is easily translatable into routine clinical practice.

  16. Differential vascular response and relationship to tumor response with photodynamic therapy using WST-09 (TOOKAD)

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    Garbo, Greta M.; Kik, Peter K.; Harrison, Linda T.; Brun, Pierre H.; Blanc, Dominique; Paulin, Pamela S.; Wieman, Thomas J.; Fingar, Victor H.

    2004-06-01

    Bacteriopheophorbide molecules are second-generation photosensitizers with promise for PHotodynamic Therapy applications due largely to their absorption peaks in the near-Infrared region. Palladium bcteriopheophorbide, also called TOOKAD, has been successfully evaluated in several pre-clinical animal models. In this study the effect on tumor and normal vasculature was evaluated using an intravital vascular model on mouse cremaster muscle implanted with the RIF tumor. For tumor response studies, the same RIF tumor was implanted intradermally on the right flank and regression was evaluated for 42 days or until the tumor reached a 12 mm diameter. A light dose 300 J/cm2 were delivered at 763 nm with power density of 100 mW/cm2. Photosensitizer dose was 4 mg/kg body weight. Mice were treated immediately, 10 minutes, 30 minutes, or 24 hours after injection. Only the higher light dose (300 J/cm2) delivered 10 minutes after injection produced a reproducible and complete vascular and tumor response after PDT in these animals. In the cremaster-tumor model, arterioles and venules partially shutdown as early as 40 minutes after the beginning of treatment, while tumor neovasculature was irreversibly closed within 20 minutes of treatment. Tumor response studies demonstrated that the magnitude of vascular stasis correlates with tumor regression studies. Further studies using this photosensitizer are warranted, given its short clearance time and its near-Infrared activation wavelength.

  17. Foetal vascular responses to thromboxane receptor blockade

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    B. A. Meyer

    1992-01-01

    Full Text Available We hypothesized that foetal administration of SQ-29,548, a putative thromboxane receptor blocker, would prevent foeto–placental vasoconstriction produced by the thromboxane mimic U46619. Arterial blood gases, continuous monitoring of maternal and foetal heart rates and blood pressures were performed in chronically catheterized pregnant ewes. Foetal blood flows and vascular resistance were determined with radioactive microspheres. SQ-29,548 effectively blocked the expected vasoconstrictive effects of thromboxane. However, prolonged infusion of SQ-29,548 resulted in significant decreases in umbilical–placental blood flow and foetal mean arterial pressure. This was accompanied by a respiratory acidemia. Potential therapy for the vasoconstrictive disorders of pregnancy with SQ-29,548 awaits further investigation of its intrinsic vasoactive properties in the umbilical–placental vasculature.

  18. Vascular delay of the latissimus dorsi provides an early hemodynamic benefit in dynamic cardiomyoplasty.

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    Ali, A T; Santamore, W P; Chiang, B Y; Dowling, R D; Tobin, G R; Slater, A D

    1999-05-01

    Dynamic cardiomyoplasty (CMP) as a surgical treatment for chronic heart failure improves functional class status for most patients. However, significant hemodynamic improvement with latissimus dorsi muscle (LDM) stimulation has not been consistent. The current protocols do not allow early LDM stimulation after CMP surgery. We hypothesized that vascular delay of LDM would increase myocardial assistance after CMP and allow early (48-h) LDM stimulation after CMP. Mongrel dogs (n = 24) were divided in four groups: 1) controls (n = 6), single-stage CMP; 2) Group ES (n = 6), single-stage CMP with early LDM stimulation beginning 48 h, postoperatively; 3) Group VD (n = 6), vascular delay of the LDM followed by CMP without early LDM stimulation, and 4) Group VDES (n = 6), vascular delay of LDM (14-18 days), followed by CMP with early stimulation (48 h postoperatively). Two weeks after CMP, global cardiac dysfunction was induced by injecting microspheres into the left coronary artery. LDM-assisted (S) beats were compared with nonstimulated beats (NS) by measuring aortic pressure (AoP), LV pressure, aortic flow, and by calculating first derivative of LV contraction (+/-dP/dt), stroke volume (SV), and stroke work (SW). In ES, LDM stimulation had no effect on the hemodynamic parameters. In the other groups, LDM stimulation significantly (p VDES. In VD, LDM stimulation increased peak AoP by 21.5+/-3.8 mm Hg, LVP by 22.1+/-4.1 mm Hg, dP/dt by 512+/-163 mm Hg/sec, SV by 10.4+/-2.3 mL, and SW by 22.1+/-5.4 g/m(-1). Similarly, in VDES, LDM stimulation increased peak AoP by 24.1+/-4.7 mm Hg, LVP by 26.2+/-4.3 mm Hg, dP/dt by 619+/-47 mm Hg/sec, SV by 6.5+/-0.7 mL, and SW by 16.7+/-4.1 g/m(-1). In dogs with global LV dysfunction, CMP after vascular delay resulted in a significant improvement in hemodynamic function measured 2 weeks after surgery. This improvement was not provided by single-stage CMP with or without early stimulation. Vascular delay of the LDM before surgery may play

  19. Plant vascular development: from early specification to differentiation.

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    De Rybel, Bert; Mähönen, Ari Pekka; Helariutta, Yrjö; Weijers, Dolf

    2016-01-01

    Vascular tissues in plants are crucial to provide physical support and to transport water, sugars and hormones and other small signalling molecules throughout the plant. Recent genetic and molecular studies have identified interconnections among some of the major signalling networks that regulate plant vascular development. Using Arabidopsis thaliana as a model system, these studies enable the description of vascular development from the earliest tissue specification events during embryogenesis to the differentiation of phloem and xylem tissues. Moreover, we propose a model for how oriented cell divisions give rise to a three-dimensional vascular bundle within the root meristem.

  20. Impact of multidisciplinary, early renal education on vascular access placement.

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    Lindberg, Jill S; Husserl, Fred E; Ross, Jamie L; Jackson, Dina; Scarlata, Debra; Nussbaum, Joyce; Cohen, Andrew; Elzein, Hafez

    2005-02-01

    The Ochsner Clinic Foundation initiated the Healthy Start Clinic to identify, educate, and refer chronic kidney disease patients to nephrologists earlier in the course of their disease. This study investigated the impact of a structured educational session on the type and timing of permanent vascular access placement in patients receiving hemodialysis. Before initiating dialysis, the HSC patient group received a general overview of the kidney and kidney disease, plus one-on-one instruction from a registered nurse, a dietitian, and a social worker. The HSC group was compared with a concurrent, conventionally prepared group of CKD patients who initiated dialysis during the same study period. Of the 147 patients initiating hemodialysis at OCF between April 1997 and December 2000, 61 had received structured HSC education, and 86 had received conventional care. In HSC-educated patients, the incidence of PVAs placed before hemodialysis initiation was twofold greater than in patients who received conventional care (77% HSC; 36% non-HSC, p < 0.001), and more HSC-educated patients initiated hemodialysis using their PVA (49% HSC; 23% non-HSC, p < 0.01). In addition, five times more patients who received HSC education received arteriovenous fistulas (52% HSC; 10% non-HSC, p < 0.001). Finally, significantly fewer HSC-educated patients initiated dialysis on a temporary catheter (51% HSC; 77% non-HSC, p < 0.001). Education programs for CKD patients help increase the number of patients receiving early PVA placement, as well as the proportion of patients receiving AVFs as opposed to grafts or temporary catheters.

  1. Early histologic, metabolic, and vascular assessment of anterior cruciate ligament autografts

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    Kleiner, J.B.; Amiel, D.; Harwood, F.L.; Akeson, W.H.

    1989-01-01

    A rabbit model for anterior cruciate ligament (ACL) reconstruction using autogenous patellar tendon was utilized to study the early events of autograft cellular dynamics. Biochemical, autoradiographic, histological, and vascular injection techniques demonstrated that the native autograft cell population rapidly necroses. This repopulation occurs without a vascular contribution; cells entering the autograft are reliant upon synovial fluid nutrition.

  2. 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

  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. Multimodality Imaging of the Long-term Vascular Responses Following Implantation of Metallic and Bioresorbable Devices

    NARCIS (Netherlands)

    V.D. Gkogkas (Vasileios)

    2014-01-01

    markdownabstract__Abstract__ The pattern of vascular responses following stent/scaffold implantation in conventional interventional practice has been assessed by coronary angiography, intravascular ultrasound or optical coherence tomography and manifests as in-stent vascular response (focal or dif

  5. Vascularized composite allograft-specific characteristics of immune responses.

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    Issa, Fadi

    2016-06-01

    Vascularized composite allograft (VCA) transplantation, or reconstructive transplantation, has revolutionized the treatment of complex tissue and functional defects. Despite arriving during an age in which the immunology of solid organ transplant rejection has been investigated in much detail, these transplants have offered new perspectives from which to explore the immunobiology of transplantation. VCAs have a number of unique molecular, cellular, and architectural features which alter the character and intensity of the rejection response. While much is yet to be clarified, an understanding of these distinct mechanisms affords new possibilities for the control of immune responses in an effort to improve outcomes after VCA transplantation.

  6. 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)....

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

    NARCIS (Netherlands)

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

    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

  8. Heterogeneous Vascular Bed Responses to Pulmonary Titanium Dioxide Nanoparticle Exposure

    Directory of Open Access Journals (Sweden)

    Alaeddin B. Abukabda

    2017-05-01

    Full Text Available A growing body of research links engineered nanomaterial (ENM exposure to adverse cardiovascular endpoints. The purpose of this study was to evaluate the impact of ENM exposure on vascular reactivity in discrete segments so that we may determine the most sensitive levels of the vasculature where these negative cardiovascular effects are manifest. We hypothesized that acute nano-TiO2 exposure differentially affects reactivity with a more robust impairment in the microcirculation. Sprague-Dawley rats (8–10 weeks were exposed to nano-TiO2via intratracheal instillation (20, 100, or 200 µg suspended per 250 µL of vehicle 24 h prior to vascular assessments. A serial assessment across distinct compartments of the vascular tree was then conducted. Wire myography was used to evaluate macrovascular active tension generation specifically in the thoracic aorta, the femoral artery, and third-order mesenteric arterioles. Pressure myography was used to determine vascular reactivity in fourth- and fifth-order mesenteric arterioles. Vessels were treated with phenylephrine, acetylcholine (ACh, and sodium nitroprusside. Nano-TiO2 exposure decreased endothelium-dependent relaxation in the thoracic aorta and femoral arteries assessed via ACh by 53.96 ± 11.6 and 25.08 ± 6.36%, respectively. Relaxation of third-order mesenteric arterioles was impaired by 100 and 20 µg nano-TiO2 exposures with mean reductions of 50.12 ± 8.7 and 68.28 ± 8.7%. Cholinergic reactivity of fourth- and fifth-order mesenteric arterioles was negatively affected by nano-TiO2 with diminished dilations of 82.86 ± 12.6% after exposure to 200 µg nano-TiO2, 42.6 ± 12.6% after 100 µg nano-TiO2, and 49.4 ± 12.6% after 20 µg nano-TiO2. Endothelium-independent relaxation was impaired in the thoracic aorta by 34.05 ± 25% induced by exposure to 200 µg nano-TiO2 and a reduction in response of 49.31 ± 25% caused by 100 µg nano-TiO2

  9. Noninvasive evaluation of the vascular response to transplantation of alginate encapsulated islets using the dorsal skin-fold model.

    Science.gov (United States)

    Krishnan, Rahul; Arora, Rajan P; Alexander, Michael; White, Sean M; Lamb, Morgan W; Foster, Clarence E; Choi, Bernard; Lakey, Jonathan R T

    2014-01-01

    Alginate encapsulation reduces the risk of transplant rejection by evading immune-mediated cell injury and rejection; however, poor vascular perfusion results in graft failure. Since existing imaging models are incapable of quantifying the vascular response to biomaterial implants after transplantation, in this study, we demonstrate the use of in vivo laser speckle imaging (LSI) and wide-field functional imaging (WiFI) to monitor the microvascular environment surrounding biomaterial implants. The vascular response to two islet-containing biomaterial encapsulation devices, alginate microcapsules and a high-guluronate alginate sheet, was studied and compared after implantation into the mouse dorsal window chamber (N = 4 per implant group). Images obtained over a 14-day period using LSI and WiFI were analyzed using algorithms to quantify blood flow, hemoglobin oxygen saturation and vascular density. Using our method, we were able to monitor the changes in the peri-implant microvasculature noninvasively without the use of fluorescent dyes. Significant changes in blood flow, hemoglobin oxygen saturation and vascular density were noted as early as the first week post-transplant. The dorsal window chamber model enables comparison of host responses to transplanted biomaterials. Future experiments will study the effect of changes in alginate composition on the vascular and immune responses.

  10. Changes in vascular responsiveness during a hyperglycemia challenge measured by near-infrared spectroscopy vascular occlusion test.

    Science.gov (United States)

    Soares, Rogério Nogueira; Reimer, Raylene A; Murias, Juan Manuel

    2017-05-01

    Postprandial hyperglycemia is associated with impaired vascular responsiveness. Recent studies have established the use of a near-infrared spectroscopy (NIRS)-derived approach, combined with a vascular occlusion test (VOT), to examine vascular responsiveness within the microvasculature in normoglycemia. The aim of this study was to examine whether this NIRS-VOT technique could detect differences in vascular responsiveness following a hyperglycemic challenge. Fourteen young healthy individuals participated in the study. Participants underwent five vascular occlusion tests (pre, 30, 60, 90 and 120min after glucose ingestion). Vascular responsiveness was determined by the slope 2 of oxygen saturation (Slope 2 StO2) and the area under the curve of oxygen saturation (StO2AUC) signal. All individuals had a significant increase in blood glucose concentration after 30min (presponsiveness to a hyperglycemic challenge, as indicated by a steeper Slope 2 StO2 and decreased StO2AUC following 90min of an oral glucose challenge. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. The early life origins of vascular ageing and cardiovascular risk: the EVA syndrome.

    Science.gov (United States)

    Nilsson, Peter M; Lurbe, Empar; Laurent, Stéphane

    2008-06-01

    Early vascular ageing is common in patients with hypertension and increased burden of cardiovascular risk factors, often influenced by chronic inflammation. One aspect of this vascular ageing is arterial stiffening, as measured by increased pulse wave velocity or augmentation index and central pressure. Several studies have indicated that this process starts early in life and that arterial function and ageing properties could be programmed during foetal life or influenced by adverse growth patterns in early postnatal life. This could explain the repeated findings in observational epidemiology that an inverse association exists between birth weight, adjusted for gestational age, and systolic blood pressure elevation in childhood, adolescence and adulthood, as well as for increased cardiovascular risk. One new marker of increased pulse pressure and arterial ageing is telomere length, as regulated by telomerase enzymatic activity. Future studies will hopefully shed light on the possibilities to halt or even reverse vascular ageing, and thereby also influence telomere biology and its different expressions.

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

    Energy Technology Data Exchange (ETDEWEB)

    Mechler, F.; Mastaglia, F.L.

    1981-02-01

    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.

  13. Multimodality Imaging of the Long-term Vascular Responses Following Implantation of Metallic and Bioresorbable Devices

    OpenAIRE

    Gkogkas, Vasileios

    2014-01-01

    markdownabstract__Abstract__ The pattern of vascular responses following stent/scaffold implantation in conventional interventional practice has been assessed by coronary angiography, intravascular ultrasound or optical coherence tomography and manifests as in-stent vascular response (focal or diffuse) or as edge vascular response (EVR) at the transition zones (focal). The utilization of bioresorbable scaffolds made of biodegradable polymers or biocorrodible metals for coronary revacularizati...

  14. Intragraft vascular occlusive sickle crisis with early renal allograft loss in occult sickle cell trait.

    Science.gov (United States)

    Kim, Lisa; Garfinkel, Marc R; Chang, Anthony; Kadambi, Pradeep V; Meehan, Shane M

    2011-07-01

    Early renal allograft failure due to sickle cell trait is rare. We present clinical and pathologic findings in 2 cases of early renal allograft failure associated with renal vein thrombosis and extensive erythrocyte sickling. Hemoglobin AS was identified in retrospect. In case 1, a 41-year-old female recipient of a deceased donor renal transplant developed abdominal pain and acute allograft failure on day 16, necessitating immediate nephrectomy. In case 2, the transplanted kidney in a 58-year-old female recipient was noted to be mottled blue within minutes of reperfusion. At 24 hours, the patient was oliguric; and the graft was removed. Transplant nephrectomies had diffuse enlargement with diffuse, nonhemorrhagic, cortical, and medullary necrosis. Extensive sickle vascular occlusion was evident in renal vein branches; interlobar, interlobular, and arcuate veins; vasa recta; and peritubular capillaries. The renal arteries had sickle vascular occlusion in case 1. Glomeruli had only focal sickle vascular occlusion. The erythrocytes in sickle vascular occlusion had abundant cytoplasmic filaments by electron microscopy. Acute rejection was not identified in either case. Protein C and S levels, factor V Leiden, and lupus anticoagulant assays were within normal limits. Hemoglobin analysis revealed hemoglobin S of 21.8% and 25.6%, respectively. Renal allograft necrosis with intragraft sickle crisis, characterized by extensive vascular occlusive erythrocyte sickling and prominent renal vein thrombosis, was observed in 2 patients with sickle cell trait. Occult sickle cell trait may be a risk factor for early renal allograft loss.

  15. Establishment of an Early Vascular Network Promotes the Formation of Ectopic Bone

    NARCIS (Netherlands)

    Eman, Rhandy M.; Meijer, Henriette A W; Öner, F. Cumhur; Dhert, Wouter J A; Alblas, Jacqueline

    2016-01-01

    Vascularization is crucial for the induction of bone formation. In this study, we investigated the application of two subtypes of peripheral blood-derived endothelial progenitor cells (EPCs) to stimulate vessel formation in ectopic bone constructs. Early and late outgrowth EPCs (E-EPC and L-EPC, res

  16. Pulmonary vascular response to digoxin in newborn lambs.

    Science.gov (United States)

    Milstein, J M; Goetzman, B W

    1984-01-01

    The effects of digoxin on pulmonary vascular resistance (PVR) were evaluated in normoxic (N) and hypoxic (H) newborn lambs with normal and elevated PVR, respectively. Lambs were anesthetized and instrumented to enable continuous measurement of mean pulmonary arterial pressure (PPA), mean left atrial pressure (PLA), mean pulmonary blood flow (Qp), and mean aortic pressure (PAO). Digoxin (10-20 micrograms/kg) was injected via central venous catheters in 11 N lambs and 4 H lambs. Under N conditions, baseline PVR was equal to 0.12 mm Hg/ml/min/kg, PPA was 33 mm Hg, PLA was 6 mm Hg, Qp was 235 ml/min/kg, and PAO was 69 mm Hg. Following digoxin, mean PVR increased by 24% (P less than 0.001) and PPA increased by 23% (P less than 0.001) for an average duration of 199 sec while QP increased by 5% (P less than 0.02) and PLA was constant suggesting a direct vasoconstrictive effect. Under H conditions, baseline PVR was equal to 0.26 mm Hg/ml/min/kg, PPA was 58 mm Hg, PLA was 4 mm Hg, Qp was 208 ml/min/kg, and PAo was 65 mm Hg. Following digoxin, mean PVR, Qp, PLA, and PAo did not change appreciably although PPA had a uniform increase of 5% (P less than 0.001). The blunted response may suggest that either the pulmonary vascular bed was maximally constricted or that digoxin and hypoxia share a common mechanism. In conclusion, digoxin has a direct pulmonary vasoconstrictor action in newborn lambs. Because of its short duration, this action probably should not alter the clinical use of this drug in newborn humans.

  17. Changes in vascular extracellular matrix composition during decidual spiral arteriole remodeling in early human pregnancy.

    Science.gov (United States)

    Smith, Samantha D; Choudhury, Ruhul H; Matos, Patricia; Horn, James A; Lye, Stephen J; Dunk, Caroline E; Aplin, John D; Jones, Rebecca L; Harris, Lynda K

    2016-05-01

    Uterine spiral arteriole (SA) remodeling in early pregnancy involves a coordinated series of events including decidual immune cell recruitment, vascular cell disruption and loss, and colonization by placental-derived extravillous trophoblast (EVT). During this process, decidual SA are converted from narrow, muscular vessels into dilated channels lacking vasomotor control. We hypothesized that this extensive alteration in SA architecture must require significant reorganization and/or breakdown of the vascular extracellular matrix (ECM). First trimester decidua basalis (30 specimens) was immunostained to identify spiral arterioles undergoing trophoblast-independent and -dependent phases of remodeling. Serial sections were then immunostained for a panel of ECM markers, to examine changes in vascular ECM during the remodeling process. The initial stages of SA remodeling were characterized by loss of laminin, elastin, fibrillin, collagen types III, IV and VI from the basement membrane, vascular media and/or adventitia, and surrounding decidual stromal cells. Loss of ECM correlated with disruption and disorganization of vascular smooth muscle cells, and the majority of changes occurred prior to extensive colonization of the vessel wall by EVT. The final stages of SA remodeling, characterized by the arrival of EVT, were associated with the increased mural deposition of fibronectin and fibrinoid. This study provides the first detailed analysis of the spatial and temporal loss of ECM from the walls of remodeling decidual SA in early pregnancy.

  18. [Early reconstruction of congenital pseudoarthrosis of the tibia with free vascularized fibular grafts].

    Science.gov (United States)

    Fernández Gómez, E; Castro Torre, M; González-Herranz, P; Delgado Sotorrío, C; Rodríguez Lorenzo, A

    2012-04-01

    Congenital pseudoarthrosis of the tibia (CPT) is an uncommon disease presenting a tibial nonunion since birth and frequently associated to neurofibromatosis type 1. Surgical management by wide excision of the pseudoarthrosis and sustitution of the defect with vascularized bone in an early stage has proven to be the most effective technique in terms of bone consolidation. We present a clinical case of a 22-month-old patient with CPT treated successfully by reconstruction with a free vascularized fibula graft with an excellent functional result.

  19. Belowground rhizomes in paleosols: The hidden half of an Early Devonian vascular plant

    Science.gov (United States)

    Xue, Jinzhuang; Deng, Zhenzhen; Huang, Pu; Huang, Kangjun; Benton, Michael J.; Cui, Ying; Wang, Deming; Liu, Jianbo; Shen, Bing; Basinger, James F.; Hao, Shougang

    2016-08-01

    The colonization of terrestrial environments by rooted vascular plants had far-reaching impacts on the Earth system. However, the belowground structures of early vascular plants are rarely documented, and thus the plant-soil interactions in early terrestrial ecosystems are poorly understood. Here we report the earliest rooted paleosols (fossil soils) in Asia from Early Devonian deposits of Yunnan, China. Plant traces are extensive within the soil and occur as complex network-like structures, which are interpreted as representing long-lived, belowground rhizomes of the basal lycopsid Drepanophycus. The rhizomes produced large clones and helped the plant survive frequent sediment burial in well-drained soils within a seasonal wet-dry climate zone. Rhizome networks contributed to the accumulation and pedogenesis of floodplain sediments and increased the soil stabilizing effects of early plants. Predating the appearance of trees with deep roots in the Middle Devonian, plant rhizomes have long functioned in the belowground soil ecosystem. This study presents strong, direct evidence for plant-soil interactions at an early stage of vascular plant radiation. Soil stabilization by complex rhizome systems was apparently widespread, and contributed to landscape modification at an earlier time than had been appreciated.

  20. Vascular wall shear stress in zebrafish model of early atherosclerosis

    Science.gov (United States)

    Choi, Woorak; Seo, Eunseok; Yeom, Eunseop; Lee, Sang Joon

    2016-11-01

    Although atherosclerosis is a multifactorial disease, the role of hemodynamic force has strong influence on the outbreak of the disease. Low and oscillating wall shear stress (WSS) is associated with the incidence of atherosclerosis. Many researchers have investigated relationships between WSS and the occurrence of atherosclerosis using in vitro and in vivo models. However, these models possess technological limitations in mimicking real biophysiological conditions and monitoring the temporal progression of atherosclerosis. In this study, a hypercholesterolaemic zebrafish model was established as a novel model to resolve these technical limitations. WSS in blood vessels of 15 days post-fertilisation zebrafish was measured using a micro PIV technique, and the spatial distribution of lipids inside blood vessels was quantitatively visualized using a confocal microscopy. As a result, lipids are mainly deposited in the regions of low WSS. The oscillating WSS is not induced by blood flows in the zebrafish disease model. The present hypercholesterolaemic zebrafish model would be useful for understanding the effect of WSS on the early stage of atherosclerosis. This work was supported by the National Research Foundation of Korea (NRF) under a Grant funded by the Korean government (MSIP) (No. 2008-0061991).

  1. Identification of key contributory factors responsible for vascular dysfunction in idiopathic recurrent spontaneous miscarriage.

    Directory of Open Access Journals (Sweden)

    Priyanka Banerjee

    Full Text Available Poor endometrial perfusion during implantation window is reported to be one of the possible causes of idiopathic recurrent spontaneous miscarriage (IRSM. We have tested the hypothesis that certain angiogenic and vasoactive factors are associated with vascular dysfunction during implantation window in IRSM and, therefore, could play a contributory role in making the endometrium unreceptive in these women. This is a prospective case-controlled study carried out on 66 women with IRSM and age and BMI matched 50 fertile women serving as controls. Endometrial expression of pro-inflammatory (IL-1β, TNF-α, IFN-γ, TGF-β1, anti-inflammatory (IL-4, -10, angiogenesis-associated cytokines (IL-2, -6, -8, angiogenic and vasoactive factors including prostaglandin E2 (PGE2, vascular endothelial growth factor (VEGF, endothelial nitric oxide synthase (eNOS, nitric oxide (NO and adrenomedullin (ADM were measured during implantation window by ELISA. Subendometrial blood flow (SEBF was assessed by color Doppler ultrasonography. Multivariate analysis was used to identify the significant factor(s responsible for vascular dysfunction in IRSM women during window of implantation and further correlated with vascular dysfunction. Endometrial expression of pro-inflammatory cytokines and PGE2 were up-regulated and anti-inflammatory and angiogenesis-associated cytokines down-regulated in IRSM women as compared with controls. Further, the angiogenic and vasoactive factors including VEGF, eNOS, NO and ADM were found to be down-regulated and SEBF grossly affected in these women. Multivariate analysis identified IL-10, followed by VEGF and eNOS as the major factors contributing towards vascular dysfunction in IRSM women. Moreover, these factors strongly correlated with blood flow impairment. This study provides an understanding that IL-10, VEGF and eNOS are the principal key components having a contributory role in endometrial vascular dysfunction in women with IRSM. Down

  2. Association Between Vascular Density and Loss of Protective RAS During Early NPDR by Fractal Dimension

    Science.gov (United States)

    Radhakrishnan, Krisnan; Vyas, Ruchi J.; Murray, Matthew; Predovic, Marina; Lim, Shiyin; Bryant, Douglas; Yaqian, Duan; Grant, Maria B.; Chalam, K. V.; Parsons-Wingerter, Patricia

    2017-01-01

    Purpose: Our hypothesis predicts that blood vessels within the retina increase in density during early-stage nonproliferative diabetic retinopathy (NPDR), based on previous results of a small retrospective study. For the current prospective study, the remodeling of arteries and veins during progression of early NPDR is assessed by a repertoire of parameters that includes the fractal dimension (D(sub f) ). In complex structures such as branching vascular trees, D(sub f) is a sensitive measure of space-filing capacity. The renin-angiotensin system (RAS) is implicated in DR pathogenesis and the function of circulating angiogenic cells (CACs), a critical bone marrow-derived population instrumental in vascular repair. Methods: Arterial and venous branching patterns were extracted from images of 6 normal controls and 3 early NPDR subjects (2 moderate, 1 mild) acquired by Heidelberg Spectralis (Registered Trademark) OCT following fluorescein angiography (FA). The vascular branching patterns were analyzed by NASAs VESsel GENeration Analysis (VESGEN) software, in which skeletonized representations were generated automatically to yield D(sub f) by the box-counting method. For binary 2D images, D(sub f) varies between limiting Euclidean dimensions of 1 and 2. Peripheral blood of diabetics and controls was collected for CD34+ CAC isolation. The gene expression of RAS in CACs was assessed by qPCR for Mas receptor to Ang-(1-7). The vasoreparative function of the CACs was measured by migration ability toward CXCL12 (SDF-1). Results: By D(sub f), venous and arterial densities were 1.370 +/- 0.006 and 1.329 +/- 0.016 for early NPDR, compared to 1.318 +/- 0.012 and 1.320 +/- 0.036 for control. The space filling capacity in early NPDR measured by D(sub f), a sensitive parameter, therefore demonstrated a pronounced increase for veins, but not for arteries. Mas receptor mRNA in CACs was increased in diabetics without DR but reduced with onset of NPDR, indicating possible loss of

  3. Early neural and vascular dysfunctions in diabetic rats are largely sequelae of increased sorbitol oxidation.

    Science.gov (United States)

    Ido, Yasuo; Nyengaard, Jens R; Chang, Kathy; Tilton, Ronald G; Kilo, Charles; Mylari, Banavara L; Oates, Peter J; Williamson, Joseph R

    2010-01-01

    These experiments were undertaken to assess the importance of cytoplasmic (c) sorbitol oxidation versus mitochondrial (m) pyruvate oxidation in mediating neural and vascular dysfunction attributable to hyperglycemia in diabetic rats. Increased oxidation of sorbitol is coupled to enzymatic reduction of free oxidized NAD(+)c to reduced NADHc, manifested by an increased ratio of NADH to NAD(+)c. Likewise, increased oxidation of pyruvate is coupled to reduction of NAD(+)m to NADHm, which increases the NADH/NAD(+)m ratio. Specific inhibitors of sorbitol production or sorbitol oxidation normalized: increased diabetic nerve NADH/NAD(+)c, impaired nerve-conduction velocity, and vascular dysfunction in sciatic nerve, retina, and aorta; however, they had little or no impact on increased NADH/NAD(+)m. These observations provide, for the first time, strong in vivo evidence for the primacy of sorbitol oxidation versus. pyruvate oxidation in mediating the metabolic imbalances, impaired nerve conduction, and vascular dysfunction evoked by diabetes. These findings are consistent with (a) the fact that oxidation of sorbitol produces "prooxidant" NADHc uncoupled from subsequent production of "antioxidant" pyruvate required for reoxidation of NADHc to NAD(+)c by lactate dehydrogenase, and (b) the hypothesis that neural and vascular dysfunction in early diabetes are caused primarily by increased NADHc, which fuels superoxide production by NADH-driven oxidases.

  4. The Influence of Normal and Early Vascular Aging on Hemodynamic Characteristics in Cardio- and Cerebrovascular Systems.

    Science.gov (United States)

    Yu, Hongtao; Huang, George P; Yang, Zifeng; Liang, Fuyou; Ludwig, Bryan

    2016-06-01

    Age-associated alterations in cardiovascular structure and function induce cardiovascular disease in elderly subjects. To investigate the effects of normal vascular aging (NVA) and early vascular aging (EVA) on hemodynamic characteristics in the circle of Willis (CoW), a closed-loop one-dimensional computational model was developed based on fluid mechanics in the vascular system. The numerical simulations revealed that higher central pulse pressure and augmentation index (AIx) appear in the EVA subjects due to early arrival of reflected waves, resulted in the increase of cardiac afterload compared with the NVA subjects. Moreover, the hemodynamic characteristics in the CoW show that the EVA subjects in an older age display a higher blood pressure than that of the NVA with a complete CoW. Herein, the increased blood pressure and flow rate coexist in the subjects with an incomplete CoW. In conclusion, the hemodynamic characteristics in the aortic tree and CoW related to aging appear to play an important role in causing cardiovascular and intravascular disease.

  5. Placental development during early pregnancy in sheep: Effects of embryo origin on vascularization

    Science.gov (United States)

    Grazul-Bilska, Anna T.; Johnson, Mary Lynn; Borowicz, Pawel P.; Bilski, Jerzy J.; Cymbaluk, Taylor; Norberg, Spencer; Redmer, Dale A.; Reynolds, Lawrence P.

    2014-01-01

    Utero-placental growth and vascular development are critical for pregnancy establishment that may be altered by various factors including assisted reproductive technologies (ART), nutrition, or others, leading to compromised pregnancy. We hypothesized that placental vascularization and expression of angiogenic factors are altered early in pregnancies after transfer of embryos created using selected ART methods. Pregnancies were achieved through natural mating (NAT), or transfer of embryos from natural mating (NAT-ET), or in vitro fertilization (IVF) or activation (IVA). Placental tissues were collected on day 22 of pregnancy. In maternal caruncles (CAR), vascular cell proliferation was less (P<0.05) for IVA than other groups. Compared to NAT, density of blood vessels was less (P<0.05) for IVF and IVA in fetal membranes (FM), and for NAT-ET, IVF and IVA in CAR. In FM, mRNA expression was decreased (P<0.01–0.08) in NAT-ET, IVF and IVA compared to NAT for vascular endothelial growth factor (VEGF) and its receptor FLT-1, placental growth factor (PGF), neuropilin (NP) 1 and 2, angiopoietin (ANGPT) 1 and 2, endothelial nitric oxide synthase (NOS3), hypoxia inducible factor-1A (HIF1A), fibroblast growth factor (FGF) 2 and its receptor FGFR2. In CAR, mRNA expression was decreased (P<0.01–0.05) in NAT-ET, IVF and IVA compared to NAT for VEGF, FLT-1, PGF, ANGPT1 and TEK. Decreased mRNA expression for 12 of 14 angiogenic factors across FM and CAR in NAT-ET, IVF and IVA pregnancies was associated with reduced placental vascular development, which would lead to poor placental function and compromised fetal and placental growth and development. PMID:24472816

  6. Early apoptotic vascular signaling is determined by Sirt1 through nuclear shuttling, forkhead trafficking, bad, and mitochondrial caspase activation.

    Science.gov (United States)

    Hou, Jinling; Chong, Zhao Zhong; Shang, Yan Chen; Maiese, Kenneth

    2010-05-01

    Complications of diabetes mellitus (DM) weigh heavily upon the endothelium that ultimately affect multiple organ systems. These concerns call for innovative treatment strategies that employ molecular pathways responsible for cell survival and longevity. Here we show in a clinically relevant model of DM with elevated D-glucose that endothelial cell (EC) SIRT1 is vital for the prevention of early membrane apoptotic phosphatidylserine externalization and subsequent DNA degradation supported by studies with modulation of SIRT1 activity and gene knockdown of SIRT1. Furthermore, during elevated D-glucose exposure, we show that SIRT1 is sequestered in the cytoplasm of ECs, but specific activation of SIRT1 shuttles the protein to the nucleus to allow for cytoprotection. The ability of SIRT1 to avert apoptosis employs the activation of protein kinase B (Akt1), the post-translational phosphorylation of the forkhead member FoxO3a, the blocked trafficking of FoxO3a to the nucleus, and the inhibition of FoxO3a to initiate a "pro-apoptotic" program as shown by complimentary gene knockdown studies of FoxO3a. Vascular apoptotic oversight by SIRT1 extends to the direct modulation of mitochondrial membrane permeability, cytochrome c release, Bad activation, and caspase 1 and 3 activation, since inhibition of SIRT1 activity and gene knockdown of SIRT1 significantly accentuate cascade progression while SIRT1 activation abrogates these apoptotic elements. Our work identifies vascular SIRT1 and its control over early apoptotic membrane signaling, Akt1 activation, post-translational modification and trafficking of FoxO3a, mitochondrial permeability, Bad activation, and rapid caspase induction as new avenues for the treatment of vascular complications during DM.

  7. Early Apoptotic Vascular Signaling is Determined by Sirt1 Through Nuclear Shuttling, Forkhead Trafficking, Bad, and Mitochondrial Caspase Activation

    Science.gov (United States)

    Hou, Jinling; Chong, Zhao Zhong; Shang, Yan Chen; Maiese, Kenneth

    2010-01-01

    Complications of diabetes mellitus (DM) weigh heavily upon the endothelium that ultimately affect multiple organ systems. These concerns call for innovative treatment strategies that employ molecular pathways responsible for cell survival and longevity. Here we show in a clinically relevant model of DM with elevated D-glucose that endothelial cell (EC) SIRT1 is vital for the prevention of early membrane apoptotic phosphatidylserine externalization and subsequent DNA degradation supported by studies with modulation of SIRT1 activity and gene knockdown of SIRT1. Furthermore, during elevated D-glucose exposure, we show that SIRT1 is sequestered in the cytoplasm of ECs, but specific activation of SIRT1 shuttles the protein to the nucleus to allow for cytoprotection. The ability of SIRT1 to avert apoptosis employs the activation of protein kinase B (Akt1), the post-translational phosphorylation of the forkhead member FoxO3a, the blocked trafficking of FoxO3a to the nucleus, and the inhibition of FoxO3a to initiate a “pro-apoptotic” program as shown by complimentary gene knockdown studies of FoxO3a. Vascular apoptotic oversight by SIRT1 extends to the direct modulation of mitochondrial membrane permeability, cytochrome c release, Bad activation, and caspase 1 and 3 activation, since inhibition of SIRT1 activity and gene knockdown of SIRT1 significantly accentuate cascade progression while SIRT1 activation abrogates these apoptotic elements. Our work identifies vascular SIRT1 and its control over early apoptotic membrane signaling, Akt1 activation, post-translational modification and trafficking of FoxO3a, mitochondrial permeability, Bad activation, and rapid caspase induction as new avenues for the treatment of vascular complications during DM. PMID:20370652

  8. Analysis of responses to kallidin, DABK, and DAK in feline hindlimb vascular bed.

    Science.gov (United States)

    Santiago, J A; Garrison, E A; Champion, H C; Smith, R E; Del Rio, O; Kadowitz, P J

    1995-12-01

    Responses to kallidin, des-Arg9-bradykinin (DABK), and des-Arg10-kallidin (DAK) were investigated in the hindlimb vascular bed of the cat under constant-flow conditions. Injections of kallidin, DABK, and DAK into the hindlimb perfusion circuit produced dose-dependent vasodilator responses in the hindlimb vascular bed. Vasodilator responses to kallidin and bradykinin (BK) were similar in magnitude and time course, and both peptides were approximately 100-fold more potent than DABK or DAK. Responses to kallidin were decreased by the kinin B2 antagonist, HOE 140, whereas responses to DABK and DAK were reduced by des-Arg9[Leu8]BK, a kinin B1-receptor antagonist. N omega-nitro-L-arginine methyl ester (L-NAME) reduced vasodilator responses to kallidin, DABK, and DAK, whereas meclofenamate, atropine, and U-37883A, a vascular selective ATP-sensitive K+ (K+ATP) channel-blocking agent, did not alter responses to the three peptides. These data suggest that both kinin B1 and B2 receptors are normally present in the hindlimb vascular bed. These data also suggest that kinin B1 and B2 receptor-mediated vasodilator responses are mediated by the release of nitric oxide and that the activation of K+ATP channels or muscarinic receptors, or the release of vasodilator prostaglandins play little if any role in mediating responses to kallidin, DABK, or DAK in the hindlimb vascular bed of the cat.

  9. Surface modification by plasma etching impairs early vascularization and tissue incorporation of porous polyethylene (Medpor(®) ) implants.

    Science.gov (United States)

    Laschke, Matthias W; Augustin, Victor A; Sahin, Fadime; Anschütz, Dieter; Metzger, Wolfgang; Scheuer, Claudia; Bischoff, Markus; Aktas, Cenk; Menger, Michael D

    2016-11-01

    Porous polyethylene (Medpor®) is commonly used in craniofacial reconstructive surgery. Rapid vascularization and tissue incorporation are crucial for the prevention of migration, extrusion, and infection of the biomaterial. Therefore, we analyzed whether surface modification by plasma etching may improve the early tissue response to Medpor®. Medpor® samples were treated in a plasma chamber at low (20 W; LE-PE) and high energy levels (40 W; HE-PE). The samples and non-treated controls were implanted into mouse dorsal skinfold chambers to analyze angiogenesis, inflammation, and granulation tissue formation over 14 days using intravital fluorescence microscopy, histology, and immunohistochemistry. Scanning electron microscopy (SEM) analyses revealed that elevating energy levels of plasma etching progressively increase the oxygen surface content and surface roughness of Medpor®. This did not affect the leukocytic response to the implants. However, LE-PE and HE-PE samples exhibited an impaired vascularization. This was associated with a reduced formation of a collagen-rich granulation tissue at the implantation site. Additional in vitro experiments showed a reduced cell attachment on plasma-etched Medpor®. Thus, plasma etching may not be recommended to improve the clinical outcome of reconstructive interventions using Medpor®. However, it may be beneficial for temporarily implanted polyethylene-based biomedical devices for which tissue incorporation is undesirable. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1738-1748, 2016. © 2015 Wiley Periodicals, Inc.

  10. Potential of advanced photoplethysmography sensing for noninvasive vascular diagnostics and early screening

    Science.gov (United States)

    Spigulis, Janis; Kukulis, Indulis; Fridenberga, Eva; Venckus, Girts

    2002-06-01

    Advanced sensor device for shape analysis of the tissue- reflected mean single period photoplethysmography (SPPPG) signals has been designed and clinically tested. The SPPPG signal shape reveals individual features of the patient's cardio-vascular state. Clinical studies of several patient groups (e.g. diabetes mellitus, atherosclerosis obliterans, Raynaud's syndrome) made possible to specify components of the SPPPG signal that are sensitive to the corresponding organic or functional pathologies. Comparison of the right and left arm finger SPPPG signal shapes, for instance, appears to be efficient tool for early screening of unilateral atherosclerosis obliterans.

  11. The Notch Ligand Delta-Like 4 Regulates Multiple Stages of Early Hemato-Vascular Development

    Science.gov (United States)

    Neves, Hélia; Gomes, Andreia C.; Saavedra, Pedro; Carvalho, Catarina C.; Duarte, António; Cidadão, António; Parreira, Leonor

    2012-01-01

    Background In mouse embryos, homozygous or heterozygous deletions of the gene encoding the Notch ligand Dll4 result in early embryonic death due to major defects in endothelial remodeling in the yolk sac and embryo. Considering the close developmental relationship between endothelial and hematopoietic cell lineages, which share a common mesoderm-derived precursor, the hemangioblast, and many key regulatory molecules, we investigated whether Dll4 is also involved in the regulation of early embryonic hematopoiesis. Methodology/Principal Findings Using Embryoid Bodies (EBs) derived from embryonic stem cells harboring hetero- or homozygous Dll4 deletions, we observed that EBs from both genotypes exhibit an abnormal endothelial remodeling in the vascular sprouts that arise late during EB differentiation, indicating that this in vitro system recapitulates the angiogenic phenotype of Dll4 mutant embryos. However, analysis of EB development at early time points revealed that the absence of Dll4 delays the emergence of mesoderm and severely reduces the number of blast-colony forming cells (BL-CFCs), the in vitro counterpart of the hemangioblast, and of endothelial cells. Analysis of colony forming units (CFU) in EBs and yolk sacs from Dll4+/− and Dll4−/− embryos, showed that primitive erythropoiesis is specifically affected by Dll4 insufficiency. In Dll4 mutant EBs, smooth muscle cells (SMCs) were seemingly unaffected and cardiomyocyte differentiation was increased, indicating that SMC specification is Dll4-independent while a normal dose of this Notch ligand is essential for the quantitative regulation of cardiomyogenesis. Conclusions/Significance This study highlights a previously unnoticed role for Dll4 in the quantitative regulation of early hemato-vascular precursors, further indicating that it is also involved on the timely emergence of mesoderm in early embryogenesis. PMID:22514637

  12. Vascular adaptive responses to physical exercise and to stress are affected differently by nandrolone administration

    Directory of Open Access Journals (Sweden)

    T. Bruder-Nascimento

    2011-04-01

    Full Text Available Androgenic anabolic steroid, physical exercise and stress induce cardiovascular adaptations including increased endothelial function. The present study investigated the effects of these conditions alone and in combination on the vascular responses of male Wistar rats. Exercise was started at 8 weeks of life (60-min swimming sessions 5 days per week for 8 weeks, while carrying a 5% body-weight load. One group received nandrolone (5 mg/kg, twice per week for 8 weeks, im. Acute immobilization stress (2 h was induced immediately before the experimental protocol. Curves for noradrenaline were obtained for thoracic aorta, with and without endothelium from sedentary and trained rats, submitted or not to stress, treated or not with nandrolone. None of the procedures altered the vascular reactivity to noradrenaline in denuded aorta. In intact aorta, stress and exercise produced vascular adaptive responses characterized by endothelium-dependent hyporeactivity to noradrenaline. These conditions in combination did not potentiate the vascular adaptive response. Exercise-induced vascular adaptive response was abolished by nandrolone. In contrast, the aortal reactivity to noradrenaline of sedentary rats and the vascular adaptive response to stress of sedentary and trained rats were not affected by nandrolone. Maximum response for 7-10 rats/group (g: sedentary 3.8 ± 0.2 vs trained 3.0 ± 0.2*; sedentary/stress 2.7 ± 0.2 vs trained/stress 3.1 ± 0.1*; sedentary/nandrolone 3.6 ± 0.1 vs trained/nandrolone 3.8 ± 0.1; sedentary/stress/nandrolone 3.2 ± 0.1 vs trained/stress/nandrolone 2.5 ± 0.1*; *P < 0.05 compared to its respective control. Stress and physical exercise determine similar vascular adaptive response involving distinct mechanisms as indicated by the observation that only the physical exercise-induced adaptive response was abolished by nandrolone.

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

    DEFF Research Database (Denmark)

    Brøgger, Torbjørn; Forman, Axel; Aalkjær, Christian;

    2014-01-01

    Background: The placenta is the base for the exchange of nutrients, oxygen and waste products for the fetus. The placental vessels hold a crucial role in regulation of blood flow, and compromised function may lead to complications like growth retardation and preeclampsia where no specific treatment...... 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...

  14. Matrix metalloproteinases limit functional recovery after spinal cord injury by modulation of early vascular events.

    Science.gov (United States)

    Noble, Linda J; Donovan, Frances; Igarashi, Takuji; Goussev, Staci; Werb, Zena

    2002-09-01

    Inflammation in general and proteinases generated as a result are likely mediators of early secondary pathogenesis after spinal cord injury. We report that matrix metalloproteinase-9 (MMP-9) plays an important role in blood-spinal cord barrier dysfunction, inflammation, and locomotor recovery. MMP-9 was present in the meninges and neurons of the uninjured cord. MMP-9 increased rapidly after a moderate contusion spinal cord injury, reaching a maximum at 24 hr, becoming markedly reduced by 72 hr, and not detectable at 7 d after injury. It was seen in glia, macrophages, neutrophils, and vascular elements in the injured spinal cord at 24 hr after injury. The natural tissue inhibitors of MMPs were unchanged over this time course. MMP-9-null mice exhibited significantly less disruption of the blood-spinal cord barrier, attenuation of neutrophil infiltration, and significant locomotor recovery compared with wild-type mice. Similar findings were observed in mice treated with a hydroxamic acid MMP inhibitor from 3 hr to 3 d after injury, compared with the vehicle controls. Moreover, the area of residual white matter at the lesion epicenter was significantly greater in the inhibitor-treated group. This study provides evidence that MMP-9 plays a key role in abnormal vascular permeability and inflammation within the first 3 d after spinal cord injury, and that blockade of MMPs during this critical period attenuates these vascular events and leads to improved locomotor recovery. Our findings suggest that early inhibition of MMPs may be an efficacious strategy for the spinal cord-injured patient.

  15. 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

    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.

  16. Short-term bryoid and vascular vegetation response to reforestation alternatives following wildfire in conifer plantations

    Science.gov (United States)

    Lori J. Kayes; Klaus J. Puettmann; Paul D. Anderson

    2011-01-01

    How are dynamics of early-seral post-fire vascular plant and bryoid (terrestrial mosses, lichens, and fungi) vegetation impacted by reforestation activities, particularly manual vegetation removal and planting density? Does the relationship between vegetation dynamics and vegetation removal differ between harsh (west-facing) and moderate (east-facing) aspects?...

  17. Analysis of the optimality principles responsible for vascular network architectonics

    CERN Document Server

    Lubashevsky, I A

    1999-01-01

    The equivalence of two optimality principles leading to Murray's law has been discussed. The first approach is based on minimization of biological work needed for maintaining the blood flow through the vessels at required level. The second one is the principle of minimal drag and lumen volume. Characteristic features of these principles are considered. An alternative approach leading to Murray's law has been proposed. For that we model the microcirculatory bed in terms of delivering vascular network with symmetrical bifurcation nodes, embedded uniformly into the cellular tissue. It was shown that Murray's law can be regarded as a direct consequence of the organism capacity for controlling the blood flow redistribution over the microcirculatory beds.

  18. Physical exercise, β-adrenergic receptors, and vascular response

    OpenAIRE

    Alexandre Sérgio Silva; Angelina Zanesco

    2010-01-01

    O exercício aeróbio promove efeitos benéficos na prevenção e tratamento de doenças como hipertensão arterial, aterosclerose, insuficiência venosa e doença arterial periférica. Os receptores β-adrenérgicos estão presentes em várias células. No sistema cardiovascular, promovem inotropismo e cronotropismo positivo cardíaco e relaxamento vascular. Embora os efeitos do exercício tenham sido investigados em receptores cardíacos, estudos focados nos vasos são escassos e controversos. Esta revis...

  19. Microfluidic technology in vascular research : the endothelial response to shear stress

    NARCIS (Netherlands)

    van der Meer, Andries Dirk

    2010-01-01

    Vascular endothelial cells form the inner lining of all blood vessels. These cells are highly responsive to the shear stress that is caused by blood flowing over their surface. In this thesis, several aspects of the endothelial response to shear stress are studied. The experiments focus on signal

  20. Internet worm early detection and response mechanism

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    In recent years, fast spreading worm has become one of the major threats to the security of the Internet and has an increasingly fierce tendency.In view of the insufficiency that based on Kalman filter worm detection algorithm is sensitive to interval, this article presents a new data collection plan and an improved worm early detection method which has some deferent intervals according to the epidemic worm propagation model, then proposes a worm response mechanism for slowing the wide and fast worm propagation effectively.Simulation results show that our methods are able to detect worms accurately and early.

  1. Assessment of tumor response to radiation and vascular targeting therapy in mice using quantitative ultrasound spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    El Kaffas, Ahmed; Sadeghi-Naini, Ali; Falou, Omar; Tran, William Tyler; Czarnota, Gregory J., E-mail: gregory.czarnota@sunnybrook.ca [Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada); Imaging Research and Physical Sciences, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada); Departments of Medical Biophysics and Radiation Oncology, Faculty of Medicine, University of Toronto, Toronto, Ontario M5G 1L7 (Canada); Zhou, Stephanie; Fernandes, Jason; Giles, Anoja [Imaging Research and Physical Sciences, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada); Hashim, Amr [Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5, Canada and Imaging Research and Physical Sciences, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada)

    2015-08-15

    Purpose: It is now recognized that the tumor vasculature is in part responsible for regulating tumor responses to radiation therapy. However, the extent to which radiation-based vascular damage contributes to tumor cell death remains unknown. In this work, quantitative ultrasound spectroscopy (QUS) methods were used to investigate the acute responses of tumors to radiation-based vascular treatments. Methods: Tumor xenografts (MDA-MB-231) were treated with single radiation doses of 2 or 8 Gy alone, or in combination with pharmacological agents that modulate vascular radiosensitivity. The midband fit, the slope, and the 0-MHz intercept QUS parameters were obtained from a linear-regression fit to the averaged power spectrum of frequency-dependent ultrasound backscatter and were used to quantify acute tumor responses following treatment administration. Power spectrums were extracted from raw volumetric radio-frequency ultrasound data obtained before and 24 h following treatment administration. These parameters have previously been correlated to tumor cell death. Staining using in situ end labeling, carbonic anhydrase 9 and cluster of differentiation 31 of tumor sections were used to assess cell death, oxygenation, and vasculature distributions, respectively. Results: Results indicate a significant midband fit QUS parameter increases of 3.2 ± 0.3 dBr and 5.4 ± 0.5 dBr for tumors treated with 2 and 8 Gy radiation combined with the antiangiogenic agent Sunitinib, respectively. In contrast, tumors treated with radiation alone demonstrated a significant midband fit increase of 4.4 ± 0.3 dBr at 8 Gy only. Preadministration of basic fibroblast growth factor, an endothelial radioprotector, acted to minimize tumor response following single large doses of radiation. Immunohistochemical analysis was in general agreement with QUS findings; an R{sup 2} of 0.9 was observed when quantified cell death was correlated with changes in midband fit. Conclusions: Results from QUS

  2. 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.

  3. Effect of Ginkgo Leaf Extract on Vascular Endothelial Function in Patients with Early Stage Diabetic Nephropathy

    Institute of Scientific and Technical Information of China (English)

    LI Xu-sheng; ZHENG Wei-ying; LOU Shi-xian; LU Xiao-wen; YE Shang-he

    2009-01-01

    Objective: To explore the effect of ginkgo leaf extract (GLE) on vascular endothelial function (VEF) in patients with early stage diabetic nephropathy (DN). Methods: Sixty-four patients were randomized equally by a randomzing digital table into two groups, the treated group and the control group. They were all treated for 8 weeks with conventional therapy for diabetes, but GLE tablets were given to the treated group additionally. Changes in VEF were estimated before and after treatment by ultrasonic examination of the brachial artery. In the meantime, changes in plasma levels of the von Willebrand factor (vWF), nitric oxide (NO) and endothelin-1 (ET-1) were observed as well. Results: The brachial arterial endothelium dependent dilating function in the treated group increased from 4.91±2.31% before treatment to 6.78±3.89% after treatment (P0.05). Conclusion: GLE could decrease the plasma level of vWF, raise the plasma NO level and improve the endothelium dependent vascular dilating function in DN patients.

  4. Vascular structure and binomial statistics for response modeling in radiosurgery of cerebral arteriovenous malformations

    Energy Technology Data Exchange (ETDEWEB)

    Andisheh, Bahram; Mavroidis, Panayiotis; Brahme, Anders; Lind, Bengt K [Department of Medical Radiation Physics, Karolinska Institutet and Stockholm University, Stockholm (Sweden); Bitaraf, Mohammad A [Department of Neurosurgery, Tehran University of Medical Sciences and Iran Gamma Knife Center, Tehran (Iran, Islamic Republic of)

    2010-04-07

    Radiation treatment of arteriovenous malformations (AVMs) has a slow and progressive vaso-occlusive effect. Some studies suggested the possible role of vascular structure in this process. A detailed biomathematical model has been used, where the morphological, biophysical and hemodynamic characteristics of intracranial AVM vessels are faithfully reproduced. The effect of radiation on plexiform and fistulous AVM nidus vessels was simulated using this theoretical model. The similarities between vascular and electrical networks were used to construct this biomathematical AVM model and provide an accurate rendering of transnidal and intranidal hemodynamics. The response of different vessels to radiation and their obliteration probability as a function of different angiostructures were simulated and total obliteration was defined as the probability of obliteration of all possible vascular pathways. The dose response of the whole AVM is observed to depend on the vascular structure of the intra-nidus AVM. Furthermore, a plexiform AVM appears to be more prone to obliteration compared with an AVM of the same size but having more arteriovenous fistulas. Finally, a binomial model was introduced, which considers the number of crucial vessels and is able to predict the dose response behavior of AVMs with a complex vascular structure.

  5. Transmembrane Protein 184A Is a Receptor Required for Vascular Smooth Muscle Cell Responses to Heparin.

    Science.gov (United States)

    Pugh, Raymond J; Slee, Joshua B; Farwell, Sara Lynn N; Li, Yaqiu; Barthol, Trista; Patton, Walter A; Lowe-Krentz, Linda J

    2016-03-01

    Vascular cell responses to exogenous heparin have been documented to include decreased vascular smooth muscle cell proliferation following decreased ERK pathway signaling. However, the molecular mechanism(s) by which heparin interacts with cells to induce those responses has remained unclear. Previously characterized monoclonal antibodies that block heparin binding to vascular cells have been found to mimic heparin effects. In this study, those antibodies were employed to isolate a heparin binding protein. MALDI mass spectrometry data provide evidence that the protein isolated is transmembrane protein 184A (TMEM184A). Commercial antibodies against three separate regions of the TMEM184A human protein were used to identify the TMEM184A protein in vascular smooth muscle cells and endothelial cells. A GFP-TMEM184A construct was employed to determine colocalization with heparin after endocytosis. Knockdown of TMEM184A eliminated the physiological responses to heparin, including effects on ERK pathway activity and BrdU incorporation. Isolated GFP-TMEM184A binds heparin, and overexpression results in additional heparin uptake. Together, these data support the identification of TMEM184A as a heparin receptor in vascular cells.

  6. Vascular Response to Experimental Stent Malapposition and Under-Expansion.

    Science.gov (United States)

    O'Brien, Caroline C; Lopes, Augusto C; Kolandaivelu, Kumaran; Kunio, Mie; Brown, Jonathan; Kolachalama, Vijaya B; Conway, Claire; Bailey, Lynn; Markham, Peter; Costa, Marco; Ware, James; Edelman, Elazer R

    2016-07-01

    Up to 80% of all endovascular stents have malapposed struts, and while some impose catastrophic events others are inconsequential. Thirteen stents were implanted in coronary arteries of seven healthy Yorkshire pigs, using specially-designed cuffed balloons inducing controlled stent malapposition and under-expansion. Optical coherence tomography (OCT) imaging confirmed that 25% of struts were malapposed (strut-wall distance strut thickness) to variable extent (max. strut-wall distance malapposed group 0.51 ± 0.05 mm vs. apposed group 0.09 ± 0.05 mm, p = 2e-3). Imaging at follow-up revealed malapposition acutely resolved (struts remained malapposed at day 5), with strong correlation between lumen and the stent cross-sectional areas (slope = 0.86, p < 0.0001, R (2) = 0.94). OCT in three of the most significantly malapposed vessels at baseline showed high correlation of elastic lamina area and lumen area (R (2) = 0.96) suggesting all lumen loss was related to contraction of elastic lamina with negligible plaque/intimal hyperplasia growth. Simulation showed this vascular recoil could be partially explained by the non-uniform strain environment created from sub-optimal expansion of device and balloon, and the inability of stent support in the malapposed region to resist recoil. Malapposition as a result of stent under-expansion is resolved acutely in healthy normal arteries, suggesting existing animal models are limited in replicating clinically observed persistent stent malapposition.

  7. 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

  8. Vascular defense responses in rice: peroxidase accumulation in xylem parenchyma cells and xylem wall thickening

    Science.gov (United States)

    Hilaire, E.; Young, S. A.; Willard, L. H.; McGee, J. D.; Sweat, T.; Chittoor, J. M.; Guikema, J. A.; Leach, J. E.

    2001-01-01

    The rice bacterial blight pathogen Xanthomonas oryzae pv. oryzae is a vascular pathogen that elicits a defensive response through interaction with metabolically active rice cells. In leaves of 12-day-old rice seedlings, the exposed pit membrane separating the xylem lumen from the associated parenchyma cells allows contact with bacterial cells. During resistant responses, the xylem secondary walls thicken within 48 h and the pit diameter decreases, effectively reducing the area of pit membrane exposed for access by bacteria. In susceptible interactions and mock-inoculated controls, the xylem walls do not thicken within 48 h. Xylem secondary wall thickening is developmental and, in untreated 65-day-old rice plants, the size of the pit also is reduced. Activity and accumulation of a secreted cationic peroxidase, PO-C1, were previously shown to increase in xylem vessel walls and lumen. Peptide-specific antibodies and immunogold-labeling were used to demonstrate that PO-C1 is produced in the xylem parenchyma and secreted to the xylem lumen and walls. The timing of the accumulation is consistent with vessel secondary wall thickening. The PO-C1 gene is distinct but shares a high level of similarity with previously cloned pathogen-induced peroxidases in rice. PO-C1 gene expression was induced as early as 12 h during resistant interactions and peaked between 18 and 24 h after inoculation. Expression during susceptible interactions was lower than that observed in resistant interactions and was undetectable after infiltration with water, after mechanical wounding, or in mature leaves. These data are consistent with a role for vessel secondary wall thickening and peroxidase PO-C1 accumulation in the defense response in rice to X. oryzae pv. oryzae.

  9. 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.

  10. 123I-FP-CIT SPECT imaging in early diagnosis of dementia in patients with and without a vascular component

    Directory of Open Access Journals (Sweden)

    Marina eGarriga

    2015-07-01

    Full Text Available Alzheimer’s disease (AD and vascular dementia (VaD are the most common cause of dementia. Cerebral ischemia is a major risk factor for development of dementia. 123I-FP-CIT SPECT (DaTScan is a complementary tool in the differential diagnoses of patients with incomplete or uncertain Parkinsonism. Additional application of DaTScan enables the categorization of Parkinsonian disease with dementia (PDD, and its differentiation from pure AD, and may further contribute to change the therapeutic decision. The aim of this study was to analyse the vascular contribution towards dementia and mild cognitive impairment (MCI. We evaluated the utility of DaTScan for the early diagnosis of dementia in patients with and without a clinical vascular component, and the association between neuropsychological function, vascular component and dopaminergic function on DaTScan. 105 patients with MCI or the initial phases of dementia were studied prospectively. We developed an initial assessment using neurologic examination, blood tests, cognitive function tests, structural neuroimaging and DaTScan. The vascular component was later quantified in two ways: clinically, according to the Framingham Risk Score and by structural neuroimaging using Wahlund Scale Total Score (WSTS. Early diagnosis of dementia was associated with an abnormal DaTScan. A significant association was found between a high WSTS and an abnormal DaTScan (p<0.01. Mixed AD was the group with the highest vascular component, followed by the VaD group, while MCI and pure AD showed similar WSTS. No significant associations were found between neuropsychological impairment and DaTScan independently of associated vascular component. DaTScan seems to be a good tool to discriminate, in a first clinical assessment, patients with MCI from those with established dementia. There was bigger general vascular affectation observable in MRI or CT in patients with abnormal dopaminergic uptake seen on DaTScan.

  11. Mixed venous O2 saturation and fluid responsiveness after cardiac or major vascular surgery

    NARCIS (Netherlands)

    A.N. Kuiper (Arjan); R.J. Trof (R.); A.B.J. Groeneveld (Johan)

    2013-01-01

    textabstractBackground: It is unclear if and how SvO2 can serve as an indicator of fluid responsiveness in patients after cardiac or major vascular surgery.Methods: This was a substudy of a randomized single-blinded clinical trial reported earlier on critically ill patients with clinical hypovolemia

  12. 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

  13. Nicolaus Copernicus and the rapid vascular responses to aldosterone.

    Science.gov (United States)

    Barton, Matthias; Meyer, Matthias R

    2015-08-01

    For decades, rapid steroid responses initiated by membrane receptors have been a primary research focus. G protein-coupled estrogen receptor (GPER) is activated by 17β-estradiol and participates in functional crosstalk with other steroid receptors. With reference to the physician and astronomer Nicolaus Copernicus (1473-1543), who used rigorous scientific approaches to shift paradigms and change dogma, we discuss whether GPER can also be considered an aldosterone receptor. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Nitrendipine: effects on vascular responses and myocardial binding.

    Science.gov (United States)

    McBride, W; Mukherjee, A; Haghani, Z; Wheeler-Clark, E; Brady, J; Gandler, T; Bush, L; Buja, L M; Willerson, J T

    1984-11-01

    We have further defined the binding characteristics of [3H]nitrendipine to myocardial microsomal membranes of cats, dogs, rats, and rabbits and to canine coronary vasculature (1.5-3.0 mm OD), and we have studied nitrendipine's effect on contractile responses in isolated feline cardiac muscle and canine coronary arteries. [3H]nitrendipine binding is rapid, saturable, and reversible in all four species and in all of these tissues. Feline myocardium has a single binding site with a dissociation constant (KD) of 1.94 nM. Canine myocardium may have two classes of binding sites, with the high-affinity site having a KD of 0.17 nM. Nitrendipine depresses contractility in isolated feline cardiac muscle and canine coronary arteries in a dose-dependent manner [half-maximal dose (ED50) 0.20 microM in isolated feline cardiac muscle and 1.6-6.3 nM for potential dependent contractile responses in isolated canine coronary arteries] and severely blunts the contractile response to increases in extracellular calcium concentration in isolated feline papillary muscles. In contrast to verapamil and D 600, nitrendipine does not prevent the treppe phenomenon. In isolated feline cardiac muscle and large canine coronary arteries, the minimal nitrendipine concentration required for specific binding and for depression of contractile responses is similar. However, only in large canine coronary arteries is the ED50 for nifedipine's depression of contractility similar to the KD for [3H]nitrendipine binding in the respective tissue.

  15. Early growth trajectories affect sexual responsiveness.

    Science.gov (United States)

    Lee, Who-Seung; Metcalfe, Neil B; Réale, Denis; Peres-Neto, Pedro R

    2014-02-22

    The trajectory of an animal's growth in early development has been shown to have long-term effects on a range of life-history traits. Although it is known that individual differences in behaviour may also be related to certain life-history traits, the linkage between early growth or development and individual variation in behaviour has received little attention. We used brief temperature manipulations, independent of food availability, to stimulate compensatory growth in juvenile three-spined sticklebacks Gasterosteus aculeatus. Here, we examine how these manipulated growth trajectories affected the sexual responsiveness of the male fish at the time of sexual maturation, explore associations between reproductive behaviour and investment and lifespan and test whether the perceived time stress (until the onset of the breeding season) influenced such trade-offs. We found a negative impact of growth rate on sexual responsiveness: fish induced (by temperature manipulation) to grow slowest prior to the breeding season were consistently quickest to respond to the presence of a gravid female. This speed of sexual responsiveness was also positively correlated with the rate of development of sexual ornaments and time taken to build a nest. However, after controlling for effects of growth rate, those males that had the greatest sexual responsiveness to females had the shortest lifespan. Moreover, the time available to compensate in size before the onset of the breeding season (time stress) affected the magnitude of these effects. Our results demonstrate that developmental perturbations in early life can influence mating behaviour, with long-term effects on longevity.

  16. Prostaglandins participate in the late phase of the vascular response to acetylcholine iontophoresis in humans.

    Science.gov (United States)

    Durand, S; Tartas, M; Bouyé, P; Koïtka, A; Saumet, J L; Abraham, P

    2004-12-15

    The participation of prostaglandins (PGs) in the cutaneous vasodilatation to acetylcholine (ACh) applied via iontophoresis is under debate. Using laser Doppler flowmetry, we studied the long lasting effect (20 min) of iontophoretic application (30 s; 0.1 mA) of ACh on the human forearm. Experiments were repeated (1) using deionized water instead of ACh to test the effect of current application, (2) after scopolamine treatment to inhibit muscarinic cholinergic receptors, and (3) 2 h, 3 days and 10 days following inhibition of PG synthesis with aspirin or a placebo control. Cutaneous vascular conductance (CVC) was calculated at rest (CVC(rest)), at peak vasodilatation in the first 5 min following ACh iontophoresis (CVC(peak)), and 20 min after iontophoresis (CVC(20)). The minimal CVC (CVC(min)) following iontophoresis was also determined. Cutaneous response to ACh displayed a biphasic pattern with an early and transient peak (CVC(peak): 62 +/- 8% of the maximal CVC induced by local heating (MVC)) followed by a long lasting slower vasodilatation (CVC(min): 44 +/- 6; CVC(20): 56 +/- 5%MVC). The current itself had no major effect. Scopolamine almost abolished both phases. The long lasting phase was aspirin sensitive but not the transient phase. At hour 2 post-aspirin, CVC(peak) was 61 +/- 10, CVC(min) 26 +/- 6 and CVC(20) 29 +/- 6%MVC. At day 3, CVC(peak) was 53 +/- 9, CVC(min) 22 +/- 3 and CVC(20) 25 +/- 4%MVC. At day 10, CVC(peak) was 67 +/- 10, CVC(min) 47 +/- 7 and CVC(20) 50 +/- 8%MVC. Placebo had no effect. We conclude that PGs participate in the vasodilator response following ACh iontophoresis. Previous non-steroidal anti-inflammatory drug treatments must be taken into account when studying the effect of ACh iontophoresis.

  17. Peripheral vascular responses to heat stress after hindlimb suspension

    Science.gov (United States)

    Looft-Wilson, Robin C.; Gisolfi, Carl V.

    2002-01-01

    PURPOSE: The purpose of this study was to determine whether hindlimb suspension (which simulates the effects of microgravity) results in impaired hemodynamic responses to heat stress or alterations in mesenteric small artery sympathetic nerve innervation. METHODS: Over 28 d, 16 male Sprague-Dawley rats were hindlimb-suspended, and 13 control rats were housed in the same type of cage. After the treatment, mean arterial pressure (MAP), colonic temperature (Tcol), and superior mesenteric and iliac artery resistances (using Doppler flowmetry) were measured during heat stress [exposure to 42 degrees C until the endpoint of 80 mm Hg blood pressure was reached (75 +/- 9 min); endpoint Tcore = 43.6 +/- 0.2] while rats were anesthetized (sodium pentobarbital, 50 mg x kg(-1) BW). RESULTS: Hindlimb-suspended and control rats exhibited similar increases in Tcol, MAP, and superior mesenteric artery resistance, and similar decreases in iliac resistance during heat stress (endpoint was a fall in MAP below 80 mm Hg). Tyrosine hydroxylase immunostaining indicated similar sympathetic nerve innervation in small mesenteric arteries from both groups. CONCLUSION: Hindlimb suspension does not alter the hemodynamic or thermoregulatory responses to heat stress in the anesthetized rat or mesenteric sympathetic nerve innervation, suggesting that this sympathetic pathway is intact.

  18. Vascular responsiveness to dimethylaminoethyl methacrylate and its degradation products.

    Science.gov (United States)

    Abebe, Worku; Maddux, William F; Schuster, George S; Lewis, Jill B

    2003-07-01

    The increasing use of acrylate-based resins in dentistry has raised questions about the biocompatibility of these substances with oral tissues. The focus of the present investigation was to assess the responsiveness of blood vessels to the resin polymerization accelerating agent dimethylaminoethyl methacrylate (DMAEMA) and its degradation products dimethylethanolamine (DME) and methacrylic acid (MAA), using the rat aortic ring preparation as a tissue model. DMAEMA induced concentration-dependent relaxation of norepinephrine (NE)-contracted aortic rings with and without endothelium. N-nitro-L-arginine methyl ester (L-NAME) selectively inhibited the endothelium-dependent relaxation induced by DMAEMA, suggesting the release of nitric oxide from the endothelium by DMAEMA. Both indomethacin and glybenclamide attenuated the vasorelaxation elicited by DMAEMA in the presence as well as in the absence of endothelium, providing evidence for the role of vasorelaxant prostanoid(s) and K(ATP) channel activation in the responses observed. On the other hand, while MAA was without any apparent effect on the rat aorta, DMAEMA at high and DME at relatively low concentrations caused contraction of the tissues with and without endothelium in the absence of NE. The DME-induced contraction was inhibited by indomethacin, suggesting the involvement of contractile arachidonic acid metabolite(s) in the action of DME. This observation was supported by the findings of increased thromboxane A(2) (TXA(2)) production in aortic rings incubated with DME. Taken together, the data suggest that both DMAEMA and its degradation product, DME, are vasoactive, inducing vasorelaxation and contraction by various mechanisms that may involve the release of nitric oxide from the endothelium, the activation of smooth muscle K(ATP) channels, and the generation of vasorelaxant prostanoid(s) and TXA(2). These effects may play a role in tissue homeostasis and certain adverse conditions associated with the use of

  19. ROCK2 primes the endothelium for vascular hyperpermeability responses by raising baseline junctional tension.

    Science.gov (United States)

    Beckers, Cora M L; Knezevic, Nebojsa; Valent, Erik T; Tauseef, Mohammad; Krishnan, Ramaswamy; Rajendran, Kavitha; Hardin, C Corey; Aman, Jurjan; van Bezu, Jan; Sweetnam, Paul; van Hinsbergh, Victor W M; Mehta, Dolly; van Nieuw Amerongen, Geerten P

    2015-07-01

    Rho kinase mediates the effects of inflammatory permeability factors by increasing actomyosin-generated traction forces on endothelial adherens junctions, resulting in disassembly of intercellular junctions and increased vascular leakage. In vitro, this is accompanied by the Rho kinase-driven formation of prominent radial F-actin fibers, but the in vivo relevance of those F-actin fibers has been debated, suggesting other Rho kinase-mediated events to occur in vascular leak. Here, we delineated the contributions of the highly homologous isoforms of Rho kinase (ROCK1 and ROCK2) to vascular hyperpermeability responses. We show that ROCK2, rather than ROCK1 is the critical Rho kinase for regulation of thrombin receptor-mediated vascular permeability. Novel traction force mapping in endothelial monolayers, however, shows that ROCK2 is not required for the thrombin-induced force enhancements. Rather, ROCK2 is pivotal to baseline junctional tension as a novel mechanism by which Rho kinase primes the endothelium for hyperpermeability responses, independent from subsequent ROCK1-mediated contractile stress-fiber formation during the late phase of the permeability response.

  20. Contribution of perfusion pressure to vascular resistance response during head-up tilt

    Science.gov (United States)

    Imadojemu, V. A.; Lott, M. E.; Gleeson, K.; Hogeman, C. S.; Ray, C. A.; Sinoway, L. I.

    2001-01-01

    We measured brachial and femoral artery flow velocity in eight subjects and peroneal and median muscle sympathetic nerve activity (MSNA) in five subjects during tilt testing to 40 degrees. Tilt caused similar increases in MSNA in the peroneal and median nerves. Tilt caused a fall in femoral artery flow velocity, whereas no changes in flow velocity were seen in the brachial artery. Moreover, with tilt, the increase in the vascular resistance employed (blood pressure/flow velocity) was greater and more sustained in the leg than in the arm. The ratio of the percent increase in vascular resistance in leg to arm was 2.5:1. We suggest that the greater vascular resistance effects in the leg were due to an interaction between sympathetic nerve activity and the myogenic response.

  1. Elevated glucose concentration and natriuretic peptides receptor response on vascular smooth muscle of spontaneously hypertensive rats.

    Science.gov (United States)

    Yasunari, K; Kohno, M; Kano, H; Hanehira, T; Minami, M; Ikeda, M; Horio, T; Yokokawa, K; Takeda, T

    1995-12-01

    1. Hyperglycaemia is believed to be a major cause of diabetic vascular complications such as accelerated atherosclerosis. In order to elucidate the effect of hyperglycaemia on vascular response in spontaneously hypertensive rats (SHR), the natriuretic peptides receptor responses to vascular smooth muscle cells (VSMC) which are thought to suppress atherosclerosis were studied under high glucose (HG:22.2 mmol/L) conditions. 2. The total number of cells in SHR is higher and natriuretic peptides receptor response is smaller than that of cells in the Wistar-Kyoto (WKY) rat. Membrane bound protein kinase C (PKC) activity in HG or SHR is higher compared to that of cells in normal glucose (NG:5.6 mmol/L) or WKY. Cells cultured in HG for at least 2 passages had higher total cell number and receptor mediated cGMP formation were suppressed compared to cells cultured in NG both in SHR and WKY. Specific PKC inhibitor PKC (19-36) 1 mu mol/L prevented HG induced suppression of natriuretic peptides response. 3. These results show that hyperglycaemia may be linked to suppressed natriuretic peptides receptor response which is caused by increased PKC activity both in WKY and SHR. This suppressed response may cause the accelerated atherosclerosis by hyperglycaemia.

  2. Time course of pulmonary vascular response to an acutely repetitive pulmonary microembolism in dogs--an analysis using pulmonary vascular impedance.

    Science.gov (United States)

    Tobise, K; Tosaka, S; Onodera, S

    1992-05-01

    To understand the mechanism leading to progressive pulmonary hypertension, we investigated the time course of vascular response to an acutely repetitive pulmonary microembolism in dogs by using pulmonary vascular impedance. In a normal state, the mean pulmonary arterial pressure (mPAP) was transiently increased by emboli, and the impedance moduli of 0 Hz (= Rin), 1.5 Hz and 3 Hz were slightly increased. A four-element electrical vascular model showed the transient increase in peripheral pulmonary vascular resistance (R2) and inertia, and reduction in compliance (C). In contrast, in a state of a slight pulmonary hypertension, mPAP was continuously increased by the same amount of emboli, and the impedance moduli of both 0 Hz and 3 Hz were significantly increased. By a four-element model, a severe increase in R2 and reduction in C were observed, and these changes continued. Therefore, although the vascular response to pulmonary microembolism basically depends on the degree of mechanical obstruction, this response is thought to be modulated by the responsiveness of pulmonary vessels at that time, which is involved in the alteration in the local characteristics of pulmonary vessels, and/or the recruitment of a new blood flow.

  3. Single passive leg movement-induced hyperemia: a simple vascular function assessment without a chronotropic response.

    Science.gov (United States)

    Venturelli, Massimo; Layec, Gwenael; Trinity, Joel; Hart, Corey R; Broxterman, Ryan M; Richardson, Russell S

    2017-01-01

    Passive leg movement (PLM)-induced hyperemia is a novel approach to assess vascular function, with a potential clinical role. However, in some instances, the varying chronotropic response induced by PLM has been proposed to be a potentially confounding factor. Therefore, we simplified and modified the PLM model to require just a single PLM (sPLM), an approach that may evoke a peripheral hemodynamic response, allowing a vascular function assessment, but at the same time minimizing central responses. To both characterize and assess the utility of sPLM, in 12 healthy subjects, we measured heart rate (HR), stroke volume, cardiac output (CO), mean arterial pressure (MAP), leg blood flow (LBF), and calculated leg vascular conductance (LVC) during both standard PLM, consisting of passive knee flexion and extension performed at 1 Hz for 60 s, and sPLM, consisting of only a single passive knee flexion and extension over 1 s. During PLM, MAP transiently decreased (5 ± 1 mmHg), whereas both HR and CO increased from baseline (6.0 ± 1.1 beats/min, and 0.8 ± 0.01 l/min, respectively). Following sPLM, MAP fell similarly (5 ± 2 mmHg; P = 0.8), but neither HR nor CO responses were identifiable. The peak LBF and LVC response was similar for PLM (993 ± 189 ml/min; 11.9 ± 1.5 ml·min(-1)·mmHg(-1), respectively) and sPLM (878 ± 119 ml/min; 10.9 ± 1.6 ml·min(-1)·mmHg(-1), respectively). Thus sPLM represents a variant of the PLM approach to assess vascular function that is more easily performed and evokes a peripheral stimulus that induces a significant hyperemia, but does not generate a potentially confounding, chronotropic response, which may make sPLM more useful clinically.

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

    Science.gov (United States)

    Paine, Nicola J; Ring, Christopher; Aldred, Sarah; Bosch, Jos A; Wadley, Alex J; Veldhuijzen van Zanten, Jet J C S

    2013-05-01

    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 participants completed a stress task under two counter balanced conditions. In the exercise condition, a morning bout of eccentric exercise (12×5 repetitions of unilateral eccentric knee extension at 120% intensity of concentric one repetition maximum) was used to increase levels of inflammatory-responsive cytokines during an afternoon stress session scheduled 6h later. In the control condition, participants sat and relaxed for 45min, 6h prior to the afternoon stress session. Forearm blood flow, calf blood flow (measured in the leg which completed the exercise task), blood pressure, heart rate and cardiac output were assessed at rest and in response to mental stress. As expected, interleukin-6 was higher (p=.02) 6h post exercise, i.e., at the start of the stress session, as compared to the no-exercise control condition. Mental stress increased forearm blood flow, calf blood flow, blood pressure, heart rate, and cardiac output in both conditions (p'sexercise condition compared to the control condition (peccentric exercise attenuated the vascular responses to mental stress locally at the site of eccentric exercise-induced inflammation. The observed impairment in vascular responses to stress associated with increased levels of inflammation suggests a mechanism through which inflammation might increase the risk for MI. Copyright © 2010 Elsevier Inc. All rights reserved.

  5. Visualization of tumor vascular reactivity in response to respiratory challenges by optical coherence tomography (Conference Presentation)

    Science.gov (United States)

    Kim, Hoon Sup; Lee, Songhyun; Lee, Kiri; Eom, Tae Joong; Kim, Jae G.

    2016-02-01

    We previously reported the potential of using vascular reactivity during respiratory challenges as a marker to predict the response of breast tumor to chemotherapy in a rat model by using a continuous wave near-infrared spectroscopy. However, it cannot visualize how the vascular reactivity from tumor vessel can predict the tumor response to its treatment. In this study, we utilized a spectral domain optical coherence tomography (SD-OCT) system to visualize vascular reactivity of both tumor and normal vasculature during respiratory challenges in a mouse model. We adapted intensity based Doppler variance algorithm to draw angiogram from the ear of mouse (8-week-old Balb/c nu/nu). Animals were anesthetized using 1.5% isoflurane, and the body temperature was maintained by a heating pad. Inhalational gas was switched from air (10min) to 100% oxygen (10min), and a pulse oximeter was used to monitor arterial oxygen saturation and heart rate. OCT angiograms were acquired 5 min after the onset of each gas. The vasoconstriction effect of hyperoxic gas on vasculature was shown by subtracting an en-face image acquired during 100% oxygen from the image acquired during air inhalation. The quantitative change in the vessel diameter was measured from the en-face OCT images of the individual blood vessels. The percentage of blood vessel diameter reduction varied from 1% to 12% depending on arterial, capillary, or venous blood vessel. The vascular reactivity change during breast tumor progression and post chemotherapy will be monitored by OCT angiography.

  6. 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

    2015-04-01

    Cardiovascular disease (CVD) remains the leading killer of women in developed nations. One sex-specific risk factor is preeclampsia, a syndrome of hypertension and proteinuria that complicates 5% of pregnancies. Although preeclampsia resolves after delivery, exposed women are at increased long-term risk of premature CVD and mortality. Pre-existing CVD risk factors are associated with increased risk of developing preeclampsia but whether preeclampsia merely uncovers risk or contributes directly to future CVD remains a critical unanswered question. A mouse preeclampsia model was used to test the hypothesis that preeclampsia causes an enhanced vascular response to future vessel injury. A preeclampsia-like state was induced in pregnant CD1 mice by overexpressing soluble fms-like tyrosine kinase-1, a circulating antiangiogenic protein that induces hypertension and glomerular disease resembling human preeclampsia. Two months postpartum, soluble fms-like tyrosine kinase-1 levels and blood pressure normalized and cardiac size and function by echocardiography and renal histology were indistinguishable in preeclampsia-exposed compared with control mice. Mice were then challenged with unilateral carotid injury. Preeclampsia-exposed mice had significantly enhanced vascular remodeling with increased vascular smooth muscle cell proliferation (180% increase; Ppreeclampsia. These data support a new model in which vessels exposed to preeclampsia retain a persistently enhanced vascular response to injury despite resolution of preeclampsia after delivery. This new paradigm may contribute to the substantially increased risk of CVD in woman exposed to preeclampsia.

  7. Effect of sodium depletion on peripheral vascular responses to heat stress in baboons.

    Science.gov (United States)

    Proppe, D W

    1987-04-01

    The cutaneous vasodilation and renal vasoconstriction in baboons during environmental heating (EH) appear to be produced predominantly by sympathetic vasoconstrictor withdrawal and activation of the renin-angiotensin system, respectively. Since these mechanisms may be influenced differently by sodium depletion, this study examined the hypothesis that sodium depletion would have a differential effect on cutaneous and renal vascular responses to EH. Sodium depletion was produced in chronically instrumented baboons by placing them on low-salt intake for 8-19 days along with diuretic administration. EH consisted of exposing the baboon to an ambient temperature of 40-42 degrees C until core temperature (Tc) reached 39.8-40.0 degrees C. Both control plasma renin activity (PRA) and the rise in PRA with Tc during EH were considerably larger in sodium-depleted baboons. However, the magnitudes of the progressive increases in iliac vascular conductance (used as an index of hindlimb cutaneous vasodilation) and renal vascular resistance with rising Tc during EH were unaltered by sodium depletion. Therefore, neither cutaneous nor renal vascular responses to EH are influenced by elevated PRA and other changes accompanying sodium depletion in the baboon.

  8. Smart(phone) Learning Experience Among Vascular Trainees Using a Response System Application.

    Science.gov (United States)

    Al-Jundi, Wissam; Kayssi, Ahmed; Papia, Giuseppe; Dueck, Andrew

    Smartphones have become the most important personal technological device. M-learning is learning through mobile device educational technology. We aim to assess the acceptability of a smartphone learning experience among the vascular trainees and determine if results could inform formal teaching efforts. A survey of the vascular trainees at a single center was conducted following a trial of smartphone learning experience. A vascular fellow used a smartphone response system application (Polltogo, Inspirapps Inc.) to send a daily multiple-choice question to the vascular residents for 20 consecutive working days. The application allows for only one attempt from each user, and the answers are registered anonymously. However, each participant receives instant feedback on his/her response by viewing the correct answer after answering each question along with a distribution of answers among other users. A total of 9 trainees participated in the trial, and all of them filled a posttrial survey. All the trainees possessed smartphones. The majority (78%) were not aware of the concept of m-learning. The mobile engagement score (number of answers received divided by total possible answers) was 145/180 (81%). All the trainees were "satisfied" or "very satisfied" with the experience, and the same number stated that they were "likely" or "very likely" to use this technology in the future. The majority (89%) agreed that such an application could assist them in preparing for their board examination. On 3 occasions, 75% or more of the participating trainees answered the multiple-choice question incorrectly, which resulted in addressing the relevant topics in the unit's weekly teaching conference. Using smartphones for education is acceptable among the vascular trainees, and the trial of a response system application with instant written feedback represents a novel method for using smartphones for collaborative learning. Such an application can also inform program directors and

  9. 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

    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...... and soluble vascular cell adhesion molecule-1 (sVCAM-1) in both wild-type and apoB transgenic mice. In wild-type mice, plasma very low-density lipoprotein cholesterol (VLDL-C) and low-density lipoprotein cholesterol (LDL-C) were unaffected by fat-feeding. ApoB transgenic mice had mildly elevated plasma LDL...... 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...

  10. 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.

  11. Diverse effects of taurine on vascular response and inflammation in GSH depletion model in rabbits.

    Science.gov (United States)

    Ozsarlak-Sozer, G; Sevin, G; Ozgur, H H; Yetik-Anacak, G; Kerry, Z

    2016-04-01

    A reduction in GSH and an increase in free radicals are observed in inflammatory diseases, indicating oxidative stress. Taurine protects cells from the cytotoxic effects of inflammation. There have been limited studies to date evaluating the effect of taurine in oxidative stress-induced vascular dysfunction and its role in vascular inflammatory diseases. Therefore, we aimed to investigate the effect of taurine on the regulation of vascular tonus and vascular inflammatory markers in rabbit aortae and carotid arteries in oxidative stress-induced by GSH depletion. Rabbits were treated subcutaneously with buthionine sulfoximine (BSO), GSH-depleting compound and/or taurine. Cumulative concentration-response curves for acetylcholine (ACh), phenylephrine and 5-hydroxytriptamine (5-HT) were constructed with or without Nω-nitro-L-arginine (LNA) in the carotid artery and aorta rings. Immunohistochemical staining was performed for TNF-α and IL-1β. BSO increased ACh-induced NO-dependent relaxations, phenylephrine-induced contractions in the carotid artery and 5-HT induced-contractions in both the carotid artery and the aorta. BSO decreased EDHF dependent relaxations only in the aorta. ACh-induced NO-dependent relaxations and augmented contractions were normalized by taurine. BSO increased TNF-α expressions in both carotid arteries and aortas, which were reversed by taurine. The BSO-induced increase in IL-1β was reversed by taurine only in aortae. Treatment with BSO resulted in vascular reactivity changes and increased immunostaining of TNF-α in mainly carotid arteries in this model of oxidative stress. The effect of taurine on BSO-induced vascular reactivity changes varied depending on the vessel. The inhibition of the increase in TNF-α expression by taurine in both carotid arteries and aortae supports the proposal that taurine has a beneficial effect in the treatment of inflammatory diseases such as atherosclerosis.

  12. 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.

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

    Science.gov (United States)

    Mahanty, Siddhartha; Orrego, Miguel Angel; Mayta, Holger; Marzal, Miguel; Cangalaya, Carla; Paredes, Adriana; Gonzales-Gustavson, Eloy; Arroyo, Gianfranco; Gonzalez, Armando E; Guerra-Giraldez, Cristina; García, Hector H; Nash, Theodore E

    2015-03-01

    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 can be used to

  14. 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

  15. The early stress responses in fish larvae.

    Science.gov (United States)

    Pederzoli, Aurora; Mola, Lucrezia

    2016-05-01

    During the life cycle of fish the larval stages are the most interesting and variable. Teleost larvae undergo a daily increase in adaptability and many organs differentiate and become active. These processes are concerted and require an early neuro-immune-endocrine integration. In larvae communication among the nervous, endocrine and immune systems utilizes several known signal molecule families which could be different from those of the adult fish. The immune-neuroendocrine system was studied in several fish species, among which in particular the sea bass (Dicentrarchus labrax), that is a species of great commercial interest, very important in aquaculture and thus highly studied. Indeed the immune system of this species is the best known among marine teleosts. In this review the data on main signal molecules of stress carried out on larvae of fish are considered and discussed. For sea bass active roles in the early immunological responses of some well-known molecules involved in the stress, such as ACTH, nitric oxide, CRF, HSP-70 and cortisol have been proposed. These molecules and/or their receptors are biologically active mainly in the gut before complete differentiation of gut-associated lymphoid tissue (GALT), probably acting in an autocrine/paracrine way. An intriguing idea emerges from all results of these researches; the molecules involved in stress responses, expressed in the adult cells of the hypothalamic-pituitary axis, during the larval life of fish are present in several other localizations, where they perform probably the same role. It may be hypothesized that the functions performed by hypothalamic-pituitary system are particularly important for the survival of the larva and therefore they comprises several other localizations of body. Indeed the larval stages of fish are very crucial phases that include many physiological changes and several possible stress both internal and environmental.

  16. Contrasting effects of ascorbate and iron on the pulmonary vascular response to hypoxia in humans.

    Science.gov (United States)

    Talbot, Nick P; Croft, Quentin P; Curtis, M Kate; Turner, Brandon E; Dorrington, Keith L; Robbins, Peter A; Smith, Thomas G

    2014-12-01

    Hypoxia causes an increase in pulmonary artery pressure. Gene expression controlled by the hypoxia-inducible factor (HIF) family of transcription factors plays an important role in the underlying pulmonary vascular responses. The hydroxylase enzymes that regulate HIF are highly sensitive to varying iron availability, and iron status modifies the pulmonary vascular response to hypoxia, possibly through its effects on HIF. Ascorbate (vitamin C) affects HIF hydroxylation in a similar manner to iron and may therefore have similar pulmonary effects. This study investigated the possible contribution of ascorbate availability to hypoxic pulmonary vasoconstriction in humans. Seven healthy volunteers undertook a randomized, controlled, double-blind, crossover protocol which studied the effects of high-dose intravenous ascorbic acid (total 6 g) on the pulmonary vascular response to 5 h of sustained hypoxia. Systolic pulmonary artery pressure (SPAP) was assessed during hypoxia by Doppler echocardiography. Results were compared with corresponding data from a similar study investigating the effect of intravenous iron, in which SPAP was measured in seven healthy volunteers during 8 h of sustained hypoxia. Consistent with other studies, iron supplementation profoundly inhibited hypoxic pulmonary vasoconstriction (P ascorbate did not affect the increase in pulmonary artery pressure induced by several hours of hypoxia (P = 0.61). We conclude that ascorbate does not interact with hypoxia and the pulmonary circulation in the same manner as iron. Whether the effects of iron are HIF-mediated remains unknown, and the extent to which ascorbate contributes to HIF hydroxylation in vivo is also unclear.

  17. 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.

  18. Physiological mechanisms of vascular response induced by shear stress and effect of exercise in systemic and placental circulation.

    Directory of Open Access Journals (Sweden)

    Iván eRodríguez

    2014-09-01

    Full Text Available Physiological vascular function regulation is essential for cardiovascular health and depends on adequate control of molecular mechanisms triggered by endothelial cells in response to mechanical and chemical stimuli induced by blood flow. Endothelial dysfunction is one of the main risk factors of cardiovascular pathology, where the imbalance between the synthesis of vasodilator and vasoconstrictor molecules is common in the development of vascular disorders in systemic and placental circulation. In the placenta, an organ without autonomic innervations, the local control of vascular tone is critical for maintenance of fetal growth and mechanisms that underlie shear stress response induced by blood flow are essential during pregnancy. In this field, shear stress induced by moderate exercise is one of the most important mechanisms to improve vascular function through nitric oxide (NO synthesis and stimulation of mechanical response of endothelial cells triggered by ion channels, caveolae, endothelial NO synthase (eNOS and vascular endothelial growth factor (VEGF, among others. The demand for oxygen and nutrients by tissues and organs, especially in placentation and pregnancy, determines blood flow parameters and physiological adaptations of vascular beds for covering metabolic requirements. In this regard, moderate exercise versus sedentarism shows potential benefits for improving vascular function associated with the enhancement of molecular mechanisms induced by shear stress. In this review, we collect evidence about molecular bases of physiological response to shear stress in order to highlight the relevance of moderate exercise-training for vascular health in adult and fetal life.

  19. Early diagnosis of diabetic vascular complications: impairment of red blood cell deformability

    Science.gov (United States)

    Shin, Sehyun; Ku, Yunhee; Park, Cheol-Woo; Suh, Jang-Soo

    2006-02-01

    Reduced deformability of red blood cells (RBCs) may play an important role on the pathogenesis of chronic vascular complications of diabetes mellitus. However, available techniques for measuring RBC deformability often require washing process after each measurement, which is not optimal for day-to-day clinical use at point of care. The objectives of the present study are to develop a device and to delineate the correlation of impaired RBC deformability with diabetic nephropathy. We developed a disposable ektacytometry to measure RBC deformability, which adopted a laser diffraction technique and slit rheometry. The essential features of this design are its simplicity (ease of operation and no moving parts) and a disposable element which is in contact with the blood sample. We studied adult diabetic patients divided into three groups according to diabetic complications. Group I comprised 57 diabetic patients with normal renal function. Group II comprised 26 diabetic patients with chronic renal failure (CRF). Group III consisted of 30 diabetic subjects with end-stage renal disease (ESRD) on hemodialysis. According to the renal function for the diabetic groups, matched non-diabetic groups were served as control. We found substantially impaired red blood cell deformability in those with normal renal function (group I) compared to non-diabetic control (P = 0.0005). As renal function decreases, an increased impairment in RBC deformability was found. Diabetic patients with chronic renal failure (group II) when compared to non-diabetic controls (CRF) had an apparently greater impairment in RBC deformability (P = 0.07). The non-diabetic cohort (CRF), on the other hand, manifested significant impairment in red blood cell deformability compared to healthy control (P = 0.0001). The newly developed slit ektacytometer can measure the RBC deformability with ease and accuracy. In addition, progressive impairment in cell deformability is associated with renal function loss in all

  20. Characterization of ionizing radiation-induced unfolded protein response in human vascular endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun Ju; Lee, Yoon Jin; Kang, Seong Man [Laboratory of Radiation Effect, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2013-04-15

    Misfolded or unfolded proteins within the endoplasmic reticulum (ER stress), viral infection, or amino acid deprivation induce eukaryotic translation initiation factor 2α phosphorylation (eIF2α) in eukaryotic cells, repressing global protein synthesis coincident with preferential translation of activating transcription factor 4 (ATF4). ATF4 is a transcriptional activator of genes involved in amino acid metabolism, cellular redox homeostasis, and regulation of apoptosis. When the eIF2α/ATF4 pathway is initiated by ER stress, the pathway is referred toas the unfolded protein response (UPR). In addition to DNA, proteins may be initial and important targets of ionizing radiation (IR), and the damaged protein can trigger ER stress pathway. Recent investigations suggested that IR induces ER stress followed by UPR in various cell types including intestinal epithelial cells. We conducted this study to determine whether IR can activate UPR in human vascular endothelial cells. Our data have shown that IR increased PERK-dependent eIF2α phosphorylation accompanied by induction in ATF4 protein levels in human vascular endothelial cells without alterations in expressions of XBP-1s and GRP78. Based on these data, we suggest that IR selectively activates PERK branch of unfolded protein response in human vascular endothelial cells.

  1. Adrenoceptor hyporeactivity is responsible for Escherichia coli endotoxin-induced acute vascular dysfunction in humans.

    Science.gov (United States)

    Pleiner, Johannes; Heere-Ress, Elisabeth; Langenberger, Herbert; Sieder, Anna E; Bayerle-Eder, Michaela; Mittermayer, Fritz; Fuchsjäger-Mayrl, Gabriele; Böhm, Johannes; Jansen, Burkhard; Wolzt, Michael

    2002-01-01

    Impaired response to catecholamines contributes to the altered hemodynamics in sepsis, which has been attributed to excessive NO formation. We have studied the systemic hemodynamic and local forearm responses and inducible NO synthase (iNOS) expression during experimental endotoxemia in humans. Escherichia coli endotoxin (lipopolysaccharide [LPS]) was administered at doses of 1 or 2 ng/kg to healthy volunteers. In 10 subjects, the systemic pressor effect of phenylephrine was assessed before and after the administration of LPS. In 9 further subjects, forearm blood flow responses to intra-arterial noradrenaline, acetylcholine, glyceryl trinitrate, and N(G)-monomethyl-L-arginine (L-NMMA) were studied at baseline and after LPS administration. Peripheral blood was collected and analyzed for iNOS mRNA and protein. Four hours after LPS, the response of systolic blood pressure (P<0.0005) and heart rate (P<0.05) to phenylephrine was significantly reduced. In the forearm, noradrenaline-induced vasoconstriction was also reduced by approximately 50% (P<0.01), but L-NMMA responsiveness was unchanged. iNOS mRNA or protein was not increased. Marked vascular adrenoceptor hyporeactivity is detectable in the absence of increased NO activity or iNOS expression in endotoxemia, arguing against major involvement of vascular iNOS activity in the acute systemic vasodilation to LPS.

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

    National Research Council Canada - National Science Library

    Mahanty, Siddhartha; Orrego, Miguel Angel; Mayta, Holger; Marzal, Miguel; Cangalaya, Carla; Paredes, Adriana; Gonzales-Gustavson, Eloy; Arroyo, Gianfranco; Gonzalez, Armando E; Guerra-Giraldez, Cristina; García, Hector H; Nash, Theodore E

    2015-01-01

    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...

  3. The alternative complement pathway aids in vascular regression during the early stages of a murine model of proliferative retinopathy.

    Science.gov (United States)

    Kim, Clifford; Smith, Kaylee E; Castillejos, Alexandra; Diaz-Aguilar, Daniel; Saint-Geniez, Magali; Connor, Kip M

    2016-03-01

    Proliferative retinopathic diseases often progress in 2 phases: initial regression of retinal vasculature (phase 1) followed by subsequent neovascularization (NV) (phase 2). The immune system has been shown to aid in vascular pruning in such retinopathies; however, little is known about the role of the alternative complement pathway in the initial vascular regression phase. Using a mouse model of oxygen-induced retinopathy (OIR), we observed that alternative complement pathway-deficient mice (Fb(-/-)) exhibited a mild decrease in vascular loss at postnatal day (P)8 compared with age- and strain-matched controls (P = 0.035). Laser capture microdissection was used to isolate the retinal blood vessels. Expression of the complement inhibitors Cd55 and Cd59 was significantly decreased in blood vessels isolated from hyperoxic retinas compared with those from normoxic control mice. Vegf expression was measured at P8 and found to be significantly lower in OIR mice than in normoxic control mice (P = 0.0048). Further examination of specific Vegf isoform expression revealed a significant decrease in Vegf120 (P = 0.00032) and Vegf188 (P = 0.0092). In conjunction with the major modulating effects of Vegf during early retinal vascular development, our data suggest a modest involvement of the alternative complement pathway in targeting vessels for regression in the initial vaso-obliteration stage of OIR. © The Author(s).

  4. α-fetoprotein, vascular endothelial growth factor receptor-1 and early recurrence of hepatoma

    Institute of Scientific and Technical Information of China (English)

    Toshiya Kamiyama; Masato Takahashi; Kazuaki Nakanishi; Hideki Yokoo; Hirofumi Kamachi; Nozomi Kobayashi; Michitaka Ozaki; Satoru Todo

    2012-01-01

    AIM: To investigate whether α-fetoprotein (AFP) and vascular endothelial growth factor receptor (VEGFR)-1 correlate with early recurrence of hepatoma/hepatocellular carcinoma (HCC). METHODS: From 2000 to 2005, 114 consecutive patients with HCC underwent primary curative hepatectomy. The mean age was 60.7 (8.7) years and 94 patients were male. The median follow-up period was 71.2 mo (range: 43-100 mo). Immediately prior to commencing laparotomy, 5 mL bone marrow was aspirated from thesternum and collected in citrate-coated test tubes. The initial 2 mL of bone marrow aspirate was discarded in each case. AFP mRNA and VEGFR-1 mRNA in the bone marrow and peripheral blood (BM-and PH-AFP mRNA and BM-and PH-VEGFR-1 mRNA, respectively) were measured by real-time quantitative reverse transcription polymerase chain reaction. As normal controls, VEGFR-1 mRNA in the bone marrow and peripheral blood was also measured in 11 living liver donors. These data were evaluated for any correlation with early recurrence, comparing clinical and pathological outcomes. RESULTS: The cut-off value of the BM-AFP mRNA and PH-AFP mRNA level in patients with HCC was set at 1.92 × 10-7 and zero, respectively, based on data from the controls. A total of 34 (29.8%) and six (5.4%) patients were positive for BM-AFP mRNA and PH-AFP mRNA, respectively. The BM-VEGFR-1 mRNA levels in all HCC patients were higher than those in the normal controls, and this was the case also for PH-VEGFR-1mRNA. The 25-percentile values for the BM-and PH-VEGFR-1 mRNA in HCC patients were used as the cut-off values for assigning the patients into two groups based on these transcript levels. The High group for BM-VEGFR-1 mRNA contained 81 (71.1%) HCC cases and the Low group was assigned 33 (28.9%) patients. These numbers for PH-VEGFR-1mRNA were 78 (75.0%) and 26 (25.0%), respectively. HCC recurred in 80 patients; in the remnant liver in 48 cases, in the remnant liver and remote tissue in 20, and in the remote tissue alone in

  5. Baroreflex-mediated heart rate and vascular resistance responses 24 h after maximal exercise

    Science.gov (United States)

    Convertino, Victor A.

    2003-01-01

    INTRODUCTION: Plasma volume, heart rate (HR) variability, and stimulus-response relationships for baroreflex control of forearm vascular resistance (FVR) and HR were studied in eight healthy men after and without performing a bout of maximal exercise to test the hypotheses that acute expansion of plasma volume is associated with 1) reduction in baroreflex-mediated HR response, and 2) altered operational range for central venous pressure (CVP). METHODS: The relationship between stimulus (DeltaCVP) and vasoconstrictive reflex response (DeltaFVR) during unloading of cardiopulmonary baroreceptors was assessed with lower-body negative pressure (LBNP, 0, -5, -10, -15, -20 mm Hg). The relationship between stimulus (Deltamean arterial pressure (MAP)) and cardiac reflex response (DeltaHR) during loading of arterial baroreceptors was assessed with steady-state infusion of phenylephrine (PE) designed to increase MAP by 15 mm Hg alone and during application of LBNP (PE+LBNP) and neck pressure (PE+LBNP+NP). Measurements of vascular volume and autonomic baroreflex responses were conducted on two different test days, each separated by at least 1 wk. On one day, baroreflex response was tested 24 h after graded cycle exercise to volitional exhaustion. On another day, measurement of baroreflex response was repeated with no exercise (control). The order of exercise and control treatments was counterbalanced. RESULTS: Baseline CVP was elevated (P = 0.04) from a control value of 10.5 +/- 0.4 to 12.3 +/- 0.4 mm Hg 24 h after exercise. Average DeltaFVR/DeltaCVP during LBNP was not different (P = 0.942) between the exercise (-1.35 +/- 0.32 pru x mm Hg-1) and control (-1.32 +/- 0.36 pru x mm Hg-1) conditions. However, maximal exercise caused a shift along the reflex response relationship to a higher CVP and lower FVR. HR baroreflex response (DeltaHR/DeltaMAP) to PE+LBNP+NP was lower (P = 0.015) after maximal exercise (-0.43 +/- 0.15 beats x min-1 x mm Hg-1) compared with the control

  6. Uhrf2 is important for DNA damage response in vascular smooth muscle cells.

    Science.gov (United States)

    Luo, Tao; Cui, Shijun; Bian, Chunjing; Yu, Xiaochun

    2013-11-08

    Emerging evidence shows that Uhrf1 plays an important role in DNA damage response for maintaining genomic stability. Interestingly, Uhrf1 has a paralog Uhrf2 in mammals. Uhrf1 and Uhrf2 share similar domain architectures. However, the role of Uhrf2 in DNA damage response has not been studied yet. During the analysis of the expression level of Uhrf2 in different tissues, we found that Uhrf2 is highly expressed in aorta and aortic vascular smooth muscle cells. Thus, we studied the role of Uhrf2 in DNA damage response in aortic vascular smooth muscle cells. Using laser microirradiation, we found that like Uhrf1, Uhrf2 was recruited to the sites of DNA damage. We dissected the functional domains of Uhrf2 and found that the TTD, PHD and SRA domains are important for the relocation of Uhrf2 to the sites of DNA damage. Moreover, depletion of Uhrf2 suppressed DNA damage-induced H2AX phosphorylation and DNA damage repair. Taken together, our results demonstrate the function of Uhrf2 in DNA damage response.

  7. Changes in vascular alpha 1- and alpha 2-adrenoceptor responsiveness by selegiline treatment.

    Science.gov (United States)

    Pelat, M; Verwaerde, P; Tran, M A; Berlan, M; Senard, J M; Montastruc, J L

    2001-08-01

    Pharmacoepidemiological studies have reported an excess of mortality with selegiline, a MAO B inhibitor used in the treatment of Parkinson's disease. The mechanism of this putative adverse effect remains unknown but an interaction with the sympathetic nervous system was suggested. The aim of the present study was to investigate the influence of selegiline (10 mg/daily, orally during one week) on vascular alpha1- and alpha2-adrenoceptor responsiveness in conscious unrestrained dogs. Selegiline significantly increased resting values of both systolic and diastolic blood pressures and noradrenaline plasma levels (HPLC) without changing heart rate. Moreover, spectral analysis of systolic blood pressure (Fast Fourier Transformation) showed that selegiline increased the relative energy of a low frequency band without modifying the total spectrum. ED 50 calculated from dose-pressor response curves with phenylephrine (after beta-blockade by propranolol), an index of alpha1-adrenoceptor response or with noradrenaline (after alpha1- and beta blockade by prazosin plus propranolol), an index of alpha2-adrenoceptor response, were significantly higher after selegiline. Selegiline failed to modify the number of platelet alpha2-adrenoceptors measured by [(3)H] RX 821002 binding. Yohimbine-induced increase in noradrenaline release was significantly more marked after selegiline. These results support the evidence that selegiline induces a vascular alpha1- and alpha2-adrenoceptor-hyposensitivity that can be explained by the increase in noradrenaline release elicited by the drug.

  8. 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.

  9. Exercício físico, receptores β-adrenérgicos e resposta vascular Physical exercise, β-adrenergic receptors, and vascular response

    Directory of Open Access Journals (Sweden)

    Alexandre Sérgio Silva

    2010-06-01

    Full Text Available O exercício aeróbio promove efeitos benéficos na prevenção e tratamento de doenças como hipertensão arterial, aterosclerose, insuficiência venosa e doença arterial periférica. Os receptores β-adrenérgicos estão presentes em várias células. No sistema cardiovascular, promovem inotropismo e cronotropismo positivo cardíaco e relaxamento vascular. Embora os efeitos do exercício tenham sido investigados em receptores cardíacos, estudos focados nos vasos são escassos e controversos. Esta revisão abordará os efeitos do exercício físico sobre os receptores β-adrenérgicos vasculares em modelos animais e humanos e os mecanismos celulares envolvidos na resposta relaxante. Em geral, os estudos mostram resultantes conflitantes, onde observam diminuição, aumento ou nenhum efeito do exercício físico sobre a resposta relaxante. Assim, os efeitos do exercício na sensibilidade β-adrenérgica vascular merecem maior atenção, e os resultados mostram que a área de fisiopatologia vascular é um campo aberto para a descoberta de novos compostos e avanços na prática clínica.Aerobic exercise promotes beneficial effects on the prevention and treatment of diseases such as arterial hypertension, atherosclerosis, venous insufficiency, and peripheral arterial disease. β-adrenergic receptors are present in a variety of cells. In the cardiovascular system, β-adrenergic receptors promote positive inotropic and chronotropic response and vasorelaxation. Although the effect of exercise training has been largely studied in the cardiac tissue, studies focused on the vascular tissue are rare and controversial. This review examines the data from studies using animal and human models to determine the effect of physical exercise on the relaxing response mediated by β-adrenergic receptors as well as the cellular mechanisms involved in this response. Studies have shown reduction, increase, or no effect of physical exercise on the relaxing response

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

    Energy Technology Data Exchange (ETDEWEB)

    Conceição-Vertamatti, Ana Gabriela; Ramos, Luiz Alberto Ferreira [Universidade Estadual de Campinas (UNICAMP), São Paulo, SP (Brazil); Calandreli, Ivy; Chiba, Aline Nunes [Universidade de São Paulo (USP), Campus Ribeirão Preto, São Paulo, SP (Brazil); Franco, Douglas Wagner [Universidade de São Paulo (USP), Campus São Carlos, São Paulo, SP (Brazil); Tfouni, Elia [Universidade de São Paulo (USP), Campus Ribeirão Preto, São Paulo, SP (Brazil); Grassi-Kassisse, Dora Maria, E-mail: doramgk@unicamp.br [Universidade Estadual de Campinas (UNICAMP), São Paulo, SP (Brazil)

    2015-03-15

    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. To evaluate the vascular response of the tetraamines trans-[Ru{sup II}(NH{sub 3}){sub 4}(Py)(NO)]{sup 3+}, trans-[Ru{sup II}(Cl)(NO) (cyclan)](PF{sub 6}){sub 2}, and trans-[Ru{sup II}(NH{sub 3}){sub 4}(4-acPy)(NO)]{sup 3+}. Aortic rings were contracted with noradrenaline (10{sup −6} M). After voltage stabilization, a single concentration (10{sup −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{sup −6} M and sodium nitroprusside at 10{sup −6} M as well as by histological examination. 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. The results indicate that the vascular effect of the evaluated complexes involved a decrease in the vascular tone induced by norepinephrine (10{sup −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

  11. Differential vascular reactivity responses acutely following ingestion of a nitrate rich red spinach extract.

    Science.gov (United States)

    Haun, Cody T; Kephart, Wesley C; Holland, Angelia M; Mobley, Christopher B; McCloskey, Anna E; Shake, Joshua J; Pascoe, David D; Roberts, Michael D; Martin, Jeffrey S

    2016-12-01

    Inorganic nitrate ingestion has been posited to affect arterial blood pressure and vascular function. We sought to determine the acute effect of a red spinach extract (RSE) high in inorganic nitrate on vascular reactivity 1-h after ingestion in peripheral conduit and resistance arteries. Fifteen (n = 15; males 8, females 7) apparently healthy subjects (aged 23.1 ± 3.3 years; BMI 27.2 ± 3.7 kg/m(2)) participated in this crossover design, double-blinded study. Subjects reported to the lab ≥2-h post-prandial and consumed RSE (1000 mg dose; ~90 mg nitrate) or placebo (PBO). Venipuncture was performed on three occasions: baseline, 30-min post-ingestion and between 65 to 75-min post-ingestion. Baseline vascular measurements [i.e., calf venous occlusion plethysmography, brachial artery flow-mediated dilation (FMD)], 30-min of continuous blood pressure (BP) and heart rate (HR) analysis, and follow-up vascular measurements beginning at 40-min post-ingestion were also performed. Humoral nitrate following RSE ingestion was significantly higher at 30- (+54 %; P = 0.039) and 65 to 75-min post-ingestion compared to baseline (+255 %, P RSE ingestion, whereas it decreased (-14.0 %; P = 0.008) following PBO ingestion. No significant differential FMD responses were detected (P > 0.05), though RH was decreased following the baseline measure in both conditions. RSE significantly increased plasma nitrate 30-min post-ingestion, but acute microvascular (i.e., resistance vasculature) reactivity increases were isolated to the lower limb and no appreciable change in brachial artery FMD was observed.

  12. Zinc oxide particles induce inflammatory responses in vascular endothelial cells via NF-{kappa}B signaling

    Energy Technology Data Exchange (ETDEWEB)

    Tsou, Tsui-Chun, E-mail: tctsou@nhri.org.tw [Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Miaoli County, Taiwan (China); Yeh, Szu-Ching; Tsai, Feng-Yuan; Lin, Ho-Jane [Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Miaoli County, Taiwan (China); Cheng, Tsun-Jen [Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University, Taipei, Taiwan (China); Chao, How-Ran [Department of Environmental Science and Engineering, National Pingtung University of Science and Technology, Neipu, Pingtung, Taiwan (China); Tai, Lin-Ai [Center for Nanomedicine Research, National Health Research Institutes, Zhunan, Miaoli County, Taiwan (China)

    2010-11-15

    This study investigated inflammatory effects of zinc oxide (ZnO) particles on vascular endothelial cells. The effects of 50 and 100-nm ZnO particles on human umbilical vein endothelial cells (HUVECs) were characterized by assaying cytotoxicity, cell proliferation, and glutathione levels. A marked drop in survival rate was observed when ZnO concentration was increased to 45 {mu}g/ml. ZnO concentrations of {<=}3 {mu}g/ml resulted in increased cell proliferation, while those of {<=}45 {mu}g/ml caused dose-dependent increases in oxidized glutathione levels. Treatments with ZnO concentrations {<=}45 {mu}g/ml were performed to determine the expression of intercellular adhesion molecule-1 (ICAM-1) protein, an indicator of vascular endothelium inflammation, revealing that ZnO particles induced a dose-dependent increase in ICAM-1 expression and marked increases in NF-{kappa}B reporter activity. Overexpression of I{kappa}B{alpha} completely inhibited ZnO-induced ICAM-1 expression, suggesting NF-{kappa}B plays a pivotal role in regulation of ZnO-induced inflammation in HUVECs. Additionally, TNF-{alpha}, a typical inflammatory cytokine, induced ICAM-1 expression in an NF-{kappa}B-dependent manner, and ZnO synergistically enhanced TNF-{alpha}-induced ICAM-1 expression. Both 50 and 100-nm ZnO particles agglomerated to similar size distributions. This study reveals an important role for ZnO in modulating inflammatory responses of vascular endothelial cells via NF-{kappa}B signaling, which could have important implications for treatments of vascular disease.

  13. 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.

  14. Antioxidants Condition Pleiotropic Vascular Responses to Exogenous H2O2: Role of Modulation of Vascular TP Receptors and the Heme Oxygenase System

    Science.gov (United States)

    Zhang, Fan; Monu, Sumit R.; Sodhi, Komal; Bellner, Lars; Lamon, Brian D.; Zhang, Yilun; Abraham, Nader G.; Nasjletti, Alberto

    2013-01-01

    Abstract Aims: Hydrogen peroxide (H2O2), a nonradical oxidant, is employed to ascertain the role of redox mechanisms in regulation of vascular tone. Where both dilation and constriction have been reported, we examined the hypothesis that the ability of H2O2 to effect vasoconstriction or dilation is conditioned by redox mechanisms and may be modulated by antioxidants. Results: Exogenous H2O2 (0.1–10.0 μM), dose-dependently reduced the internal diameter of rat renal interlobular and 3rd-order mesenteric arteries (pantioxidants, including tempol, pegylated superoxide dismutase (PEG-SOD), butylated hydroxytoluene (BHT), and biliverdin (BV). However, as opposed to tempol or PEG-SOD, BHT & BV, antioxidants targeting radicals downstream of H2O2, also uncovered vasodilation. Innovations: Redox-dependent vasoconstriction to H2O2 was blocked by inhibitors of cyclooxygenase (COX) (indomethacin-10 μM), thromboxane (TP) synthase (CGS13080-10 μM), and TP receptor antagonist (SQ29548-1 μM). However, H2O2 did not increase vascular thromboxane B2 release; instead, it sensitized the vasculature to a TP agonist, U46619, an effect reversed by PEG-SOD. Antioxidant-conditioned dilatory response to H2O2 was accompanied by enhanced vascular heme oxygenase (HO)-dependent carbon monoxide generation and was abolished by HO inhibitors or by HO-1 & 2 antisense oligodeoxynucleotides treatment of SD rats. Conclusion: These results demonstrate that H2O2 has antioxidant-modifiable pleiotropic vascular effects, where constriction and dilation are brought about in the same vascular segment. H2O2-induced oxidative stress increases vascular TP sensitivity and predisposes these arterial segments to constrictor prostanoids. Conversely, vasodilation is reliant upon HO-derived products whose synthesis is stimulated only in the presence of antioxidants targeting radicals downstream of H2O2. Antioxid. Redox Signal. 18, 471–480. PMID:22867102

  15. Neural and vascular variability and the fMRI-BOLD response in normal aging.

    Science.gov (United States)

    Kannurpatti, Sridhar S; Motes, Michael A; Rypma, Bart; Biswal, Bharat B

    2010-05-01

    Neural, vascular and structural variables contributing to the blood oxygen level-dependent (BOLD) signal response variability were investigated in younger and older humans. Twelve younger healthy human subjects (six male and six female; mean age: 24 years; range: 19-27 years) and 12 older healthy subjects (five male and seven female; mean age: 58 years; range: 55-71 years) with no history of head trauma and neurological disease were scanned. Functional magnetic resonance imaging measurements using the BOLD contrast were made when participants performed a motor, cognitive or a breath hold (BH) task. Activation volume and the BOLD response amplitude were estimated for the younger and older at both group and subject levels. Mean activation volume was reduced by 45%, 40% and 38% in the elderly group during the motor, cognitive and BH tasks, respectively, compared to the younger. Reduction in activation volume was substantially higher compared to the reduction in the gray matter volume of 14% in the older compared to the younger. A significantly larger variability in the intersubject BOLD signal change occurred during the motor task, compared to the cognitive task. BH-induced BOLD signal change between subjects was significantly less-variable in the motor task-activated areas in the younger compared to older whereas such a difference between age groups was not observed during the cognitive task. Hemodynamic scaling using the BH signal substantially reduced the BOLD signal variability during the motor task compared to the cognitive task. The results indicate that the origin of the BOLD signal variability between subjects was predominantly vascular during the motor task while being principally a consequence of neural variability during the cognitive task. Thus, in addition to gray matter differences, the type of task performed can have different vascular variability weighting that can influence age-related differences in brain functional response.

  16. 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.

  17. Phorbol ester and atrial natriuretic peptide receptor response on vascular smooth muscle.

    Science.gov (United States)

    Yasunari, K; Kohno, M; Murakawa, K; Yokokawa, K; Horio, T; Takeda, T

    1992-04-01

    At least two types of receptors for natriuretic peptides have been reported: biologically active receptors coupled with guanylate cyclase (atrial natriuretic peptide [ANP]-B receptors) and clearance receptors (ANP-C receptors). To elucidate the role of protein kinase C (PKC) in the regulation of ANP-B receptors, vascular smooth muscle cells in culture were treated with phorbol ester. Incubation with receptor agonists and phorbol ester led to the desensitization of receptor-mediated cyclic guanosine monophosphate (ANP-B receptor response) in rat vascular smooth muscle cells. Although a PKC inhibitor and downregulation of PKC by long-term incubation of cells with phorbol esters blocked the phorbol ester-induced desensitization of the ANP-B receptor response, they did not block the ANP-induced desensitization of the ANP-B receptor response. In addition, when desensitization by phorbol esters was observed, ANP was still capable of desensitization. These observations suggest that the mechanism for regulating ANP-B receptor sensitivity may be both PKC-dependent and PKC-independent and mediated by phorbol esters and ANP, respectively.

  18. Renal responses to central vascular expansion are suppressed at night in conscious primates

    Science.gov (United States)

    Kass, D. A.; Sulzman, F. M.; Fuller, C. A.; Moore-Ede, M. C.

    1980-01-01

    The renal and hemodynamic responses of squirrel monkeys to central vascular volume expansion induced by lower body positive pressure (LBPP) during the day and night are investigated. Twelve unanesthetized animals trained to sit in a metabolism chair in which they were restrained only at the waist by a partition separating upper and lower body chambers were subjected to 4 h of continuous LBPP during the day and night, and hemodynamic, urinary and drinking data were monitored. LBPP during day and night is found to induce similar increases in central venous pressure, rises in heart rate and elevations in mean arterial blood pressure. However, although daytime LBPP induced a significant increase in urine flow and sodium excretion, a marked nocturnal inhibition of the renal response to LBPP is observed. Analysis of the time course and circadian regulation patterns of the urinary responses suggests that several separate efferent control pathways are involved.

  19. Endothelial dysfunction and decreased vascular responsiveness in the anterior cruciate ligament-deficient model of osteoarthritis.

    Science.gov (United States)

    Miller, Daniel; Forrester, Kevin; Hart, David A; Leonard, Catherine; Salo, Paul; Bray, Robert C

    2007-03-01

    Chronic inflammation associated with osteoarthritis (OA) may alter normal vascular responses and contribute to joint degradation. Vascular responses to vasoactive mediators were evaluated in the medial collateral ligament (MCL) of the anterior cruciate ligament (ACL)-deficient knee. Chronic joint instability and progressive OA were induced in rabbit knees by surgical transection of the ACL. Under halothane anesthesia, laser speckle perfusion imaging (LSPI) was used to measure MCL blood flow in unoperated control (n = 12) and 6-wk ACL-transected knees (n = 12). ACh, bradykinin, histamine, substance P (SP), and prostaglandin E(2) (PGE(2)) were applied to the MCL vasculature in topical boluses of 100 microl (dose range 10(-14) to 10(-8) mol). In normal joints, ACh, bradykinin, histamine, and PGE(2) evoked a dilatory response. Substance P caused a biphasic response that was dilatory from 10(-14) to 10(-11) mol and constricting at higher doses. In ACL-deficient knees, ACh, bradykinin, histamine, and SP decreased perfusion, whereas PGE(2) had a biphasic response that decreased perfusion at 10(-14) to 10(-11) mol and was dilatory at higher concentrations. Sodium nitroprusside increased perfusion in resting and phenylephrine-precontracted vessels with no significant differences between ACL-transected and control knees. Femoral artery occlusion and release increased perfusion by 74.3 +/- 11.1% in control knees but only by 25.8 +/- 4.4% in ACL-deficient knees. The altered responsiveness of the MCL vasculature to these inflammatory mediators may indicate endothelial dysfunction in the MCL, which may contribute to the progression and severity of OA and to the adaptation of the joint in an altered mechanical environment.

  20. 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

  1. Increased vascular permeability and nitric oxide production in response to hypoxia in the pineal gland.

    Science.gov (United States)

    Kaur, C; Sivakumar, V; Lu, J; Ling, E A

    2007-04-01

    This study examined the factors that may be involved in altering the function of pineal gland in hypoxic conditions. Adult Wistar rats were subjected to hypoxia and the pineal gland was examined for the mRNA and protein expression of hypoxia-inducible factor-1alpha (HIF-1alpha), vascular endothelial growth factor (VEGF), endothelial, neuronal and inducible nitric oxide synthase (eNOS, nNOS, iNOS) at 3 hr-14 days after hypoxic exposure by real time reverse transcription-polymerase chain reaction, Western blotting and immunohistochemistry. Upregulated mRNA and protein expression of HIF-1alpha, VEGF, eNOS, nNOS and iNOS was observed in response to hypoxia. VEGF concentrations as determined by enzyme immunoassay and nitric oxide (NO) production measured by colorimetric assay were significantly higher after hypoxic exposure when compared with the controls. Melatonin content of the pineal gland, as determined by ELISA, was significantly reduced after the hypoxic exposure. Dilated blood vessels expressing eNOS were observed in hypoxic rats. Cells immunoreactive for VEGF were identified as the astrocytes whereas those immunoreactive for iNOS were pinealocytes and macrophages. Our findings indicate that excess production of VEGF and NO in pineal gland in response to hypoxia may be involved in increased vascular permeability as evidenced by an enhanced leakage of rhodamine isothiocyanate (RhIC). The increased vascular permeability may allow free access of serum-derived substances in the pineal gland that may affect the secretory function of the pinealocytes. Administration of exogenous melatonin may be beneficial as it reduced VEGF concentration and NO production significantly in hypoxic rats, and leakage of RhIC was concomitantly reduced.

  2. Glycocalyx modulates the motility and proliferative response of vascular endothelium to fluid shear stress.

    Science.gov (United States)

    Yao, Yu; Rabodzey, Aleksandr; Dewey, C Forbes

    2007-08-01

    Flow-induced mechanotransduction in vascular endothelial cells has been studied over the years with a major focus on putative connections between disturbed flow and atherosclerosis. Recent studies have brought in a new perspective that the glycocalyx, a structure decorating the luminal surface of vascular endothelium, may play an important role in the mechanotransduction. This study reports that modifying the amount of the glycocalyx affects both short-term and long-term shear responses significantly. It is well established that after 24 h of laminar flow, endothelial cells align in the direction of flow and their proliferation is suppressed. We report here that by removing the glycocalyx by using the specific enzyme heparinase III, endothelial cells no longer align under flow after 24 h and they proliferate as if there were no flow present. In addition, confluent endothelial cells respond rapidly to flow by decreasing their migration speed by 40% and increasing the amount of vascular endothelial cadherin in the cell-cell junctions. These responses are not observed in the cells treated with heparinase III. Heparan sulfate proteoglycans (a major component of the glycocalyx) redistribute after 24 h of flow application from a uniform surface profile to a distinct peripheral pattern with most molecules detected above cell-cell junctions. We conclude that the presence of the glycocalyx is necessary for the endothelial cells to respond to fluid shear, and the glycocalyx itself is modulated by the flow. The redistribution of the glycocalyx also appears to serve as a cell-adaptive mechanism by reducing the shear gradients that the cell surface experiences.

  3. Aspects of Subcortical Ischaemic Vascular Disease : Early clinical manifestations and associations with Type 2 diabetes mellitus

    NARCIS (Netherlands)

    Harten, van B.

    2006-01-01

    Summary Subcortical ischaemic vascular disease (SIVD) is an important cause of cognitive impairment in elderly patients. Screening and diagnostic tests are needed to identify these patients. The HIV dementia scale (HDS) is a reliable and quantitative scale for identifying HIV dementia1. The cogniti

  4. Aspects of Subcortical Ischaemic Vascular Disease : Early clinical manifestations and associations with Type 2 diabetes mellitus

    NARCIS (Netherlands)

    Harten, van B.

    2006-01-01

    Summary Subcortical ischaemic vascular disease (SIVD) is an important cause of cognitive impairment in elderly patients. Screening and diagnostic tests are needed to identify these patients. The HIV dementia scale (HDS) is a reliable and quantitative scale for identifying HIV dementia1. The

  5. Retinal Vascular Fractals Correlate With Early Neurodegeneration in Patients With Type 2 Diabetes Mellitus

    DEFF Research Database (Denmark)

    Frydkjaer-Olsen, Ulrik; Soegaard Hansen, Rasmus; Pedersen, Knud

    2015-01-01

    Purpose: To investigate the correlation between the retinal vascular fractal dimension (Fd) and neurodegenerative changes in patients with no or mild diabetic retinopathy (DR). Methods: In this cross-sectional study we examined 103 patients with type 2 diabetes mellitus (T2DM) with no or mild DR....

  6. Early Vascular Damage in Young Women with DM-1 and Its Relation to Anti-Müllerian Hormone: A Cross-Sectional Study

    Directory of Open Access Journals (Sweden)

    Annelien C. de Kat

    2016-01-01

    Full Text Available Vascular function is suggested to be associated with ovarian reserve, but the relationship with microvascular function has never been studied. In this cross-sectional pilot study, the relationship of microvascular damage markers with AMH was studied in premenopausal women. Twenty-two regularly cycling women with type 1 diabetes (DM-1 and a reference group of 20 healthy regularly cycling women were included, from whom blood was drawn in the early follicular phase of the menstrual cycle. The main outcome was the correlation between circulating progenitor cells (CPCs, markers for early vascular damage, and AMH, a marker for ovarian reserve. Secondary endpoints for early vascular impairment were circulating angiogenic cells and additional biomarkers. Median AMH levels were 2.2 µg/L [1.2–3.5] in the DM-1 group and 2.1 µg/L [0.85–3.8] in the reference group. CPCs were significantly decreased in women with DM-1; 1204±537 CD34+/CD45dim cells were counted in the DM-1 group, compared to 2264±1124 in the reference group. CPCs and other markers of early vascular damage were not correlated with AMH levels in a multivariable analysis. These results underscore previous findings of early vascular damage in DM-1 and suggest that there may not be a relationship between vascular function and ovarian reserve. Trial Registration. This trial is registered with Clinicaltrials.gov NCT01665716.

  7. Cell-Cell Interactions Mediate the Response of Vascular Smooth Muscle Cells to Substrate Stiffness

    Science.gov (United States)

    Sazonova, Olga V.; Lee, Kristen L.; Isenberg, Brett C.; Rich, Celeste B.; Nugent, Matthew A.; Wong, Joyce Y.

    2011-01-01

    The vessel wall experiences progressive stiffening with age and the development of cardiovascular disease, which alters the micromechanical environment experienced by resident vascular smooth muscle cells (VSMCs). In vitro studies have shown that VSMCs are sensitive to substrate stiffness, but the exact molecular mechanisms of their response to stiffness remains unknown. Studies have also shown that cell-cell interactions can affect mechanotransduction at the cell-substrate interface. Using flexible substrates, we show that the expression of proteins associated with cell-matrix adhesion and cytoskeletal tension is regulated by substrate stiffness, and that an increase in cell density selectively attenuates some of these effects. We also show that cell-cell interactions exert a strong effect on cell morphology in a substrate-stiffness dependent manner. Collectively, the data suggest that as VSMCs form cell-cell contacts, substrate stiffness becomes a less potent regulator of focal adhesion signaling. This study provides insight into the mechanisms by which VSMCs respond to the mechanical environment of the blood vessel wall, and point to cell-cell interactions as critical mediators of VSMC response to vascular injury. PMID:21806930

  8. Analysis of the uniaxial and multiaxial mechanical response of a tissue-engineered vascular graft.

    Science.gov (United States)

    Mauri, Arabella; Zeisberger, Steffen M; Hoerstrup, Simon P; Mazza, Edoardo

    2013-03-01

    Tissue engineering is aimed at the fabrication of autologous cardiovascular implants, for example, heart valves or vascular grafts. To date, the mechanical characterization of tissue-engineered vascular grafts (TEVGs) has focused mainly on the material's strength and not on the deformation behavior. A total of 31 samples obtained from 3 mature grafts (out of the cells of a single donor) were tested in uniaxial stress and uniaxial strain configurations to characterize their stiffness under uniaxial and biaxial stress states, respectively. Corresponding measurements were carried out on samples of an ovine artery. A physiological stiffness parameter was defined for data analysis and the uniaxial and multiaxial response compared, also in terms of anisotropy. The tension-strain curve of uniaxial stress tests is highly nonlinear, whereas the results show a more gradual deformation response of the material under a uniaxial strain configuration, which better represents the physiological state of biaxial stress. Stiffness parameters and anisotropy factors are significantly influenced by the selection of the testing configuration. Tangent stiffness of a TEVG at physiological loading conditions is significantly (p<0.05) higher for uniaxial stress as compared to uniaxial strain. The same is observed for the ovine tissue. The anisotropy of the scaffold is shown to partially transfer to the mature TEVG. The results of this study show that for a TEVG characterization, a physiological biaxial testing configuration should be preferred to the commonly used uniaxial stress.

  9. Comparison of in vivo immune responses following transplantation of vascularized and non-vascularized human dermo-epidermal skin substitutes.

    Science.gov (United States)

    Klar, Agnes S; Biedermann, Thomas; Simmen-Meuli, Claudia; Reichmann, Ernst; Meuli, Martin

    2017-03-01

    Autologous bio-engineered dermo-epidermal skin substitutes (DESS) represent an alternative therapeutic option for a definitive treatment of skin defects in human patients. Largely, the interaction of host immune cells with transplanted DESS is considered to be essential for the granulation tissue formation, graft take, and its functionality. The aim of this study was to compare the spatiotemporal distribution and density of host-derived monocytes/macrophages and granulocytes in vascularized (vascDESS) versus non-vascularized DESS (non-vascDESS) in a rat model. Keratinocytes and the stromal vascular fraction (SVF) were derived from human skin or human adipose tissue, respectively. Human SVF containing both endothelial and mesenchymal/stromal progenitors was used to develop a vascularized collagen type I-based dermal component in vitro. The donor-matched, monolayer-expanded adipose stromal cells lacking endothelial cells were used as a negative control. Subsequently, human keratinocytes were seeded on top of hydrogels to build dermo-epidermal skin grafts. After transplantation onto full-thickness skin wounds on the back of immuno-incompetent rats, grafts were excised and analyzed after 1 and 3 weeks. The expression of distinct inflammatory cell markers specific for host-derived monocytes/macrophages (CD11b, CD68) or granulocytes (HIS48) was analyzed by immunofluorescence microscopy. All skin grafts were infiltrated by host-derived monocytes/macrophages (CD11b(+), CD68(+)) and granulocytes (HIS48(+)) between 1-3 week post-transplantation. When compared to non-vascDESS, the vascDESS showed an increased granulocyte infiltration at all time points analyzed with the majority of cells scattered throughout the whole dermal part. Whereas a moderate number of rat monocytes/macrophages (CD11b(+), CD68(+)) were found in vascDESS at 1 week, only a few cells were detected in non-vascDESS. We observed a time-dependent decrease of monocytes/macrophages in all transplants at 3

  10. Cyclosporin A Inhibits Smooth Muscle Proliferation in the Vascular Response to Injury

    Science.gov (United States)

    Jonasson, Lena; Holm, Jan; Hansson, Goran K.

    1988-04-01

    The arterial response to injury is dominated by proliferation of smooth muscle cells and infiltration of blood-borne cells in the vascular intima. Arterial smooth muscle cell proliferation is under growth factor control, but how this regulation operates in vivo is unclear. We studied the effect on arterial response to mechanical injury of cyclosporin A, a drug that inhibits T-lymphocyte activation. Cyclosporin A treatment at surgery caused a persistent inhibition of the intimal proliferative lesion. Cyclosporin A also inhibited expression of Ia antigens on smooth muscle cells in situ but had no direct effects on smooth muscle cell proliferation in culture. Therefore, the inhibition of intimal cell proliferation appears to be mediated via the immune system.

  11. Vascular and inflammatory high fat meal responses in young healthy men; a discriminative role of IL-8 observed in a randomized trial.

    Directory of Open Access Journals (Sweden)

    Diederik Esser

    Full Text Available BACKGROUND: High fat meal challenges are known to induce postprandial low-grade inflammation and endothelial dysfunction. This assumption is largely based on studies performed in older populations or in populations with a progressed disease state and an appropriate control meal is often lacking. Young healthy individuals might be more resilient to such challenges. We therefore aimed to characterize the vascular and inflammatory response after a high fat meal in young healthy individuals. METHODS: In a double-blind randomized cross-over intervention study, we used a comprehensive phenotyping approach to determine the vascular and inflammatory response after consumption of a high fat shake and after an average breakfast shake in 20 young healthy subjects. Both interventions were performed three times. RESULTS: Many features of the vascular postprandial response, such as FMD, arterial stiffness and micro-vascular skin blood flow were not different between shakes. High fat/high energy shake consumption was associated with a more pronounced increase in blood pressure, heart rate, plasma concentrations of IL-8 and PBMCs gene expression of IL-8 and CD54 (ICAM-1, whereas plasma concentrations of sVCAM1 were decreased compared to an average breakfast. CONCLUSION: Whereas no difference in postprandial response were observed on classical markers of endothelial function, we did observe differences between consumption of a HF/HE and an average breakfast meal on blood pressure and IL-8 in young healthy volunteers. IL-8 might play an important role in dealing with high fat challenges and might be an early marker for endothelial stress, a stage preceding endothelial dysfunction.

  12. Early alterations in vascular contractility associated to changes in fatty acid composition and oxidative stress markers in perivascular adipose tissue

    Directory of Open Access Journals (Sweden)

    Rimorini Laura

    2010-10-01

    Full Text Available Abstract Aim To test the early effect of fructose-induced changes in fatty acid composition and oxidative stress markers in perivascular adipose tissue (PVAT upon vascular contractility. Methods Adult male Wistar rats were fed a commercial diet without (CD or with 10% fructose (FRD in the drinking water for 3 weeks. We measured plasma metabolic parameters, lipid composition and oxidative stress markers in aortic PVAT. Vascular contractility was measured in aortic rings sequentially, stimulated with serotonin (5-HT and high K+-induced depolarization using intact and thereafter PVAT-deprived rings. Results Comparable body weights were recorded in both groups. FRD rats had increased plasma triglyceride and fructosamine levels. Their PVAT had an increased saturated to mono- or poly-unsaturated fatty acid ratio, a significant decrease in total superoxide dismutase and glutathione peroxidase activities and in the total content of glutathione. Conversely, lipid peroxidation (TBARS, nitric oxide content, and gluthathione reductase activity were significantly higher, indicating an increase in oxidative stress. In aortic rings, removal of PVAT increased serotonin-induced contractions, but the effect was significantly lower in rings from FRD rats. This effect was no longer observed when the two contractions were performed in PVAT-deprived rings. PVAT did not affect the contractions triggered by high K+-induced depolarization either in CD or FRD rats. Conclusions FRD induces multiple metabolic and endocrine systemic alterations which also alter PVAT and the vascular relaxant properties of this tissue. The changes in PVAT would affect its paracrine modulation of vascular function.

  13. 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.

  14. Vascular Profile Characterization of Liver Tumors by Magnetic Resonance Imaging Using Hemodynamic Response Imaging in Mice

    Directory of Open Access Journals (Sweden)

    Yifat Edrei

    2011-03-01

    Full Text Available Recently, we have demonstrated the feasibility of using hemodynamic response imaging (HRI, a functional magnetic resonance imaging (MRI method combined with hypercapnia and hyperoxia, for monitoring vascular changes during liver pathologies without the need of contrast material. In this study, we evaluated HRI ability to assess changes in liver tumor vasculature during tumor establishment, progression, and antiangiogenic therapy. Colorectal adenocarcinoma cells were injected intrasplenically to model colorectal liver metastasis (CRLM and the Mdr2 knockout mice were used to model primary hepatic tumors. Hepatic perfusion parameters were evaluated using the HRI protocol and were compared with contrast-enhanced (CE MRI. The hypovascularity and the increased arterial blood supply in well-defined CRLM were demonstrated by HRI. In CRLM-bearing mice, the entire liver perfusion was attenuated as the HRI maps were significantly reduced by 35%. This study demonstrates that the HRI method showed enhanced sensitivity for small CRLM (1–2 mm detection compared with CE-MRI (82% versus 38%, respectively. In addition, HRI could demonstrate the vasculature alteration during CRLM progression (arborized vessels, which was further confirmed by histology. Moreover, HRI revealed the vascular changes induced by rapamycin treatment. Finally, HRI facilitates primary hepatic tumor characterization with good correlation to the pathologic differentiation. The HRI method is highly sensitive to subtle hemodynamic changes induced by CRLM and, hence, can function as an imaging tool for understanding the hemodynamic changes occurring during CRLM establishment, progression, and antiangiogenic treatment. In addition, this method facilitated the differentiation between different types of hepatic lesions based on their vascular profile noninvasively.

  15. Factors influencing the early outcome of major lower limb amputation for vascular disease.

    OpenAIRE

    Campbell, W. B.; Marriott, S; Eve, R; Mapson, E.; Sexton, S.; Thompson, J F

    2001-01-01

    A consecutive series of 349 primary lower limb amputations for vascular disease, done during 1992-1998, were reviewed for amputation level, revision, complications and death, seeking associations with the American Society of Anesthesiology (ASA) grade and pre-operative co-morbidities of patients. Attempted revascularisation, and seniority of surgeon supervising the amputation were also examined for their possible influence on outcome. There were 312 patients (163 male) aged 39-92 years (media...

  16. Impact of oxidative stress during pregnancy on fetal epigenetic patterns and early origin of vascular diseases.

    Science.gov (United States)

    Ávila, Jose Guillermo Ortega; Echeverri, Isabella; de Plata, Cecilia Aguilar; Castillo, Andrés

    2015-01-01

    Epidemiological studies have led scientists to postulate the developmental origins of health and disease hypothesis for noncommunicable diseases such as diabetes, cardiovascular diseases, hypertension, and obesity. However, the cellular and molecular mechanisms involved in the development of these diseases are not well understood. In various animal models, it has been observed that oxidative stress during pregnancy is associated with the early development of endothelial dysfunction in offspring. This phenomenon suggests that endothelial dysfunction may initiate in the uterus and could lead to increased risk of cardiovascular disease later in life. Currently, it is known that many of the fetal adaptive responses to environmental factors are mediated by epigenetic changes in the genome, especially by the degree of methylation in cytosines in the promoter regions of genes. These findings suggest that the establishment of a particular epigenetic pattern in the genome may be generated by oxidative stress. © The Author(s) 2014. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  17. 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.

  18. Early Intervention of Didang Decoction on MLCK Signaling Pathways in Vascular Endothelial Cells of Type 2 Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Shoujiao Ye

    2016-01-01

    Full Text Available In the study, type 2 diabetic rat model was established using streptozotocin (STZ combined with a high-fat diet, and the rats were divided into control and diabetic groups. Diabetic groups were further divided into nonintervening, simvastatin, Didang Decoction (DDD early-phase intervening, DDD mid-phase intervening, and DDD late-phase intervening groups. The expression level of MLCK was detected using Western Blot analysis, and the levels of cyclic adenosine monophosphate (cAMP, protein kinase C (PKC, and protein kinase A (PKA were examined using Real Time PCR. Under the electron microscope, the cells in the early-DDD-intervention group and the simvastatin group were significantly more continuous and compact than those in the diabetic group. Compared with the control group, the expression of cAMP-1 and PKA was decreased in all diabetic groups, whereas the expression of MLCK and PKC was increased in early- and mid-phase DDD-intervening groups (P<0.05; compared with the late-phase DDD-intervening group, the expression of cAMP-1 and PKA was higher, but the level of MLCK and PKC was lower in early-phase DDD-intervening group (P<0.05. In conclusion, the early use of DDD improves the permeability of vascular endothelial cells by regulating the MLCK signaling pathway.

  19. Attenuation of endothelin-1-induced calcium response by tyrosine kinase inhibitors in vascular smooth muscle cells.

    Science.gov (United States)

    Liu, C Y; Sturek, M

    1996-06-01

    Although tyrosine kinases play an important role in cell growth and have been implicated in regulation of smooth muscle contraction, their role in agonist-induced myoplasmic Ca2+ responses is unclear. We examined effects of the tyrosine kinase inhibitors genistein and methyl 2,5-dihydroxycinnamate (MDHC) on the endothelin-1 (ET-1)-induced Ca2+ response and determined underlying mechanisms for the effects. Freshly isolated smooth muscle cells from porcine coronary arteries were loaded with fura 2 ester, and myoplasmic free Ca2+ (Ca2+ (m)) concentration was estimated with fura 2 microfluorometry. Both genistein and MDHC inhibited the initial transient Cam2+ response to ET by 54 and 81%, respectively (P latent period from ET-1 application to the beginning of the Cam2+ response being increased from 1.08 +/- 0.17 to 2.65 +/- 0.52 min (P < 0.05). In the absence of extracellular Ca2+, genistein inhibited the ET-1-induced Cam2+ response by 93% (P < 0.05). The Cam2+ responses to caffeine (5 mM) or inositol trisphosphate (IP3) applied intracellularly via a patch-clamp pipette were not affected by genistein. Both genistein and MDHC also abolished the sustained Cam2+ response to ET-1. However, the Cam2+ response to depolarization by 80 mM K+ was not inhibited by MDHC and only inhibited 22% by genistein (P < 0.05). These results indicate that 1) activation of tyrosine kinases is an important regulatory mechanism for the ET-1-induced Cam2+ response in vascular smooth muscle and 2) tyrosine kinases mediate ET-1-induced Ca2+ release with no direct effect on IP3-mediated Ca2+ release. Thus ET-1-mediated signaling upstream of IP3 interaction with the Ca2+ stores is regulated by tyrosine kinases.

  20. Early vascular alterations in SLE and RA patients--a step towards understanding the associated cardiovascular risk.

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    Maria José Santos

    Full Text Available Accelerated atherosclerosis represents a major problem in both systemic lupus erythematosus (SLE and rheumatoid arthritis (RA patients, and endothelial damage is a key feature of atherogenesis. We aimed to assess early endothelial changes in SLE and RA female patients (127 SLE and 107 RA without previous CV events. Biomarkers of endothelial cell activation (intercellular adhesion molecule-1 (sICAM-1, vascular cell adhesion molecule-1 (sVCAM-1, thrombomodulin (TM, and tissue factor (TF were measured and endothelial function was assessed using peripheral artery tonometry. Reactive hyperemia index (RHI, an indicator of microvascular reactivity, and augmentation index (AIx, a measure of arterial stiffness, were obtained. In addition, traditional CV risk factors, disease activity and medication were determined. Women with SLE displayed higher sICAM-1 and TM and lower TF levels than women with RA (p = 0.001, p<0.001 and p<0.001, respectively. These differences remained significant after controlling for CV risk factors and medication. Serum levels of vascular biomarkers were increased in active disease and a moderate correlation was observed between sVCAM-1 levels and lupus disease activity (rho = 0.246 and between TF levels and RA disease activity (rho = 0.301. Although RHI was similar across the groups, AIx was higher in lupus as compared to RA (p = 0.04. Also in active SLE, a trend towards poorer vasodilation was observed (p = 0.06. In conclusion, women with SLE and RA present with distinct patterns of endothelial cell activation biomarkers not explained by differences in traditional CV risk factors. Early vascular alterations are more pronounced in SLE which is in line with the higher CV risk of these patients.

  1. 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.

  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

    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.

  3. Impaired vascular responses to relaxin in diet-induced overweight female rats.

    NARCIS (Netherlands)

    Drongelen, J. van; Koppen, A. van; Pertijs, J.C.L.M.; Gooi, J.H.; Parry, L.J.; Sweep, F.C.; Lotgering, F.K.; Smits, P.; Spaanderman, M.E.A.

    2012-01-01

    Relaxin mediates renal and mesenteric vascular adaptations to pregnancy by increasing endothelium-dependent vasodilation and compliance and decreasing myogenic reactivity. Diet-induced overweight and obesity are associated with impaired endothelial dysfunction and vascular remodeling leading to a re

  4. Pioglitazone does not affect vascular or inflammatory responses after endotoxemia in humans.

    Science.gov (United States)

    Schaller, G; Kolodjaschna, J; Pleiner, J; Mittermayer, F; Kapiotis, S; Schmetterer, L; Wolzt, M

    2008-08-01

    PPARgamma agonists have been proposed to exert more than metabolic benefits, particularly by anti-inflammatory mechanisms. We hypothesized that pioglitazone might modulate inflammatory and vascular responses to lipopolysaccharide (LPS). In a placebo-controlled parallel-group study in 18 healthy male subjects, the E. coli endotoxin model of inflammation (20 IU/kg i. v.) was employed to test the effect of 60 mg pioglitazone over nine days on inflammatory cytokines. Macrovascular function and microvascular blood flow were assessed by brachial artery ultrasound and retinal blood flow parameters, respectively. Pioglitazone increased brachial artery diameter by 5.6% but had no effect on other outcome parameters under resting conditions. LPS increased cytokine levels to peak concentrations of 91.3+/-22.5 ng/ml (IL-6), 261.4+/-60.0 ng/ml (TNFalpha), and 524.5+/-15.3 ng/ml (VCAM-1). The endotoxin caused microvascular vasodilation and increased retinal white blood cell flux, while baseline brachial artery diameter remained unchanged. Pioglitazone had no effect on inflammatory cytokine or adhesion molecule release but mitigated LPS-induced hypotension (p<0.05). Neither brachial artery function nor microvascular blood flow was altered by pioglitazone. In conclusion, acute immune reactions to LPS are not affected by pioglitazone, which exerts subtle vascular effects alone and during endotoxemia. The anti-inflammatory properties of short-term pioglitazone to endotoxins in healthy subjects are therefore limited.

  5. Metabolomic profiling of cellular responses to carvedilol enantiomers in vascular smooth muscle cells.

    Directory of Open Access Journals (Sweden)

    Mingxuan Wang

    Full Text Available Carvedilol is a non-selective β-blocker indicated in the treatment of hypertension and heart failure. Although the differential pharmacological effects of individual Carvedilol enantiomer is supported by preceding studies, the cellular response to each enantiomer is not well understood. Here we report the use of GC-MS metabolomic profiling to study the effects of Carvedilol enantiomers on vascular smooth muscle cells (A7r5 and to shed new light on molecular events underlying Carvedilol treatment. The metabolic analysis revealed alternations in the levels of 8 intracellular metabolites and 5 secreted metabolites in A7r5 cells incubated separately with S- and R-Carvedilol. Principal component analysis of the metabolite data demonstrated the characteristic metabolic signatures in S- and R-Carvedilol-treated cells. A panel of metabolites, including L-serine, L-threonine, 5-oxoproline, myristic acid, palmitic acid and inositol are closely correlated to the vascular smooth muscle contraction. Our findings reveal the differentiating metabolites for A7r5 cells incubated with individual enantiomer of Carvedilol, which opens new perspectives to employ metabolic profiling platform to study chiral drug-cell interactions and aid their incorporation into future improvement of β-blocker therapy.

  6. Early quantitative evaluation of treatment response to the tumor target agent in phase I trial by contrast-enhanced ultrasound with vascular recognition imaging%超声造影在肿瘤血管靶向药物Ⅰ期临床试验疗效评价中的应用价值

    Institute of Scientific and Technical Information of China (English)

    刘隆忠; 裴小青; 李安华; 郑玮; 李毓红

    2011-01-01

    Objectives To evaluate the early effects of a tumor targeted a-gent-M2ES ( phase Ⅰ trial ) in the patients with hepatic metastatic carcinoma and the feasibility of vascular recognition imaging ( VRI ) in the quantitative assessment of these effects. Methods Nine patients ( nine tumors ) with hepatic metastatic carcinoma were classified into three groups. M2ES were administrated in 15 mg/m2 ( n = 4 ), 30 mg/m2( n = 3 ), 60 mg/m2 ( n = 2 ) once a week for three weeks, respectively. VRI was performed with an Aplio XG scanner before the treatment and on days 2, 7, 9,14, 16, and 21 after the treatment. The percentage of contrast uptake before and after treatment was evaluated by two radiologists. Quantification was performed using Image-Pro Plus6 software. All patients were rated as the responders or non-responders. The former mean decrease of contrast agent uptake after treatment exceeded a percentage of 10% than that before treatment. The changes in the percentage of contrast agent uptake at each VRI examination were statistically compared. Results A total of 59 VRI examinations were performed. Responders included three patients with nine VRI examinations after treatment and the mean contrast agent uptake decreased to 53.1 %. The uptake of responders or non-responders was of statistical significance( P < 0. 05 ). Conclusion VRI is a noninvasive real-time contrast-enhanced ultrasound imaging technique in early quantitative evaluation of tumor perfusion for M2ES in the patients with hepatic metastatic carcinoma ( phase Ⅰ trial).%目的 探讨低机械指数实时超声造影技术--血管识别成像技术(VRI)在肿瘤血管靶向药物聚乙二醇重组人血管内皮抑制素(代号M2ES)Ⅰ期临床试验疗效评估中的应用价值.方法 9例肝转移癌患者,给药剂量分别为15 mg/m2(4例)、30 mg/m2(3例)、60 mg/m2(2例),每周给药1次,共3次,用药结束后观察7 d.每例患者于治疗前及每次给药后的第2、7天

  7. 6A3-5/Osa2 is an Early Activated Gene Implicated in the Control of Vascular Smooth Muscle Cell Functions

    Directory of Open Access Journals (Sweden)

    Gwenaele Garin

    2006-01-01

    Full Text Available Vascular smooth muscle cells (VSMC growth plays a key role in the pathophysiology of vascular diseases. However, the molecular mechanisms controlling gene transcription in VSMC remain poorly understood. We previously identified, by differential display, a new gene (6A3-5 overexpressed in proliferating rat VSMC. In this study, we have cloned the full-length cDNA by screening a rat foetal brain cDNA library and investigated its functions. The 6A3-5 protein shows 4 putative conserved functional motifs: a DNA binding domain called ARID (AT-rich interaction domain, two recently described motifs (Osa Homology Domain, and a nuclear localization signal. The deduced protein sequence was observed to be 85% identical to the recently described human Osa2 gene. Immunolabelling, using an anti-6A3-5/Osa2 monoclonal antibody, showed a nuclear localization of the 6A3-5/Osa2 protein. In addition, PDGF upregulated 6A3-5/Osa2 expression at both the transcript and protein levels in a dose and time-dependent fashion. The pattern of upregulation by PDGF was reminiscent of the early responsive gene c-fos. The PDGF-induced upregulation of 6A3-5/Osa2 and proliferation of VSMC were significantly inhibited in a dose and sequence-dependent fashion by an antisense, but not by sense, scrambled or mismatched oligonucleotides directed against 6A3-5/Osa2. In VSMC of aortas derived from hypertensive (LH rats, 6A3-5/Osa2 is overexpressed as compared to that in normotensive (LL rats. The 6A3-5/Osa2-gene expression is downregulated by an ACE inhibitor and upregulated by exogenous AngiotensinII in LH rats. In summary, these results indicate that 6A3-5/Osa2 is an early activated gene that belongs to a new family of proteins involved in the control of VSMC growth.

  8. 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...... patients without or with early DR, and to examine whether neurodegeneration precedes visible vasculopathy in the pathogenesis of DR. METHODS: A systematic literature search was performed to identify studies which used optical coherence tomography (OCT) or multifocal electroretinography (mfERG) to detect...

  9. Role of Na + -K + ATPase enzyme in vascular response of goat ruminal artery

    Directory of Open Access Journals (Sweden)

    Kathirvel K

    2009-01-01

    Full Text Available Objective: To study the role of Na + , K + - ATPase enzyme in the vascular response of goat ruminal artery. Materials and Methods: Ruminal artery was obtained in chilled aerated modified Krebs-Henseleit solution (KHS from a local slaughterhouse and transported in ice for further processing. The endothelium intact arterial ring was mounted in a thermostatically controlled (37 ± 0.5°C organ bath containing 20 ml of modified KHS (pH 7.4 bubbled with oxygen (95% and CO 2 (5% under 2g tension. An equilibration of 90 min was allowed before addition of drugs into the bath. The responses were recorded isometrically in an automatic organ bath connected to PowerLab data acquisition system. In order to examine intact functional endothelium, ACh (10µM was added on the 5-HT (1.0µM - induced sustained contractile response. Similarly, functional characterization of Na + , K + -ATPase activity was done by K + -induced relaxation (10µM-10mM in the absence and presence of ouabain (0.1µM/ 0.1mM, digoxin (0.1µM and barium (30µM. Results: ACh (10-5 M did not produce any relaxing effect on 5-HT-induced sustained contractile response suggesting that vascular endothelium has no significant influence on the activation of sodium pump by extracellular K + in ruminal artery. Low concentration of Ba 2+ (30 µM (IC 50 : 0.479mM inhibited K + -induced relaxation suggesting K ir (inward rectifier channel in part had role in K + -induced vasodilatation in ruminal artery. Vasorelaxant effect of KCl (10µM-10mM in K + -free medium is also blocked by ouabain (0.1µM and 0.1mM (IC 50 :0.398mM and IC 35 : 1.36mM, but not by digoxin (0.1µM (IC 50 0.234mM suggesting that ouabain sensitive Na + , K + -ATPase isoform is present in the ruminal artery. Conclusion: In the goat ruminal artery functional regulation of sodium pump is partly mediated by K + channel and ouabain sensitive Na + , K + ATPase.

  10. The effect of microdialysis needle trauma on cutaneous vascular responses in humans.

    Science.gov (United States)

    Hodges, Gary J; Chiu, Caroline; Kosiba, Wojciech A; Zhao, Kun; Johnson, John M

    2009-04-01

    Microdialysis enables in-depth mechanistic study of the cutaneous circulation in humans. However, whether the insertion or presence of the microdialysis fiber (MDF) affects the skin circulation or its responses is unknown. We tested whether the cutaneous vascular response to whole body heating (WBH) was affected by MDF or by pretreatment with ice (part 1) or local anesthesia (LA; part 2). Eleven subjects participated, 9 in part 1 and 8 in part 2 (5 participated in both). In both parts, four sites on the forearm were selected, providing untreated control, MDF only, ice or LA only, and combined MDF plus ice or LA. A tube-lined suit controlled whole body skin temperature, which was raised to approximately 38 degrees C for WBH. Skin sites were instrumented with laser-Doppler flow probes. Data were expressed as cutaneous vascular conductance (CVC). Baseline levels were not different among sites (P > 0.05). In part 1, the internal temperature for the onset of vasodilation was higher (P > 0.05) with MDF with or without ice pretreatment than at untreated control sites (control 36.6 +/- 0.1 degrees C, Ice 36.5 +/- 0.1, MDF 36.8 +/- 0.1 degrees C, and Ice+MDF 36.8 +/- 0.1 degrees C). Peak CVC during WBH was decreased (P MDF (control 73 +/- 7 vs. MDF 59 +/- 6% of maximal CVC). Ice (73 +/- 6% of maximal CVC) or Ice+MDF (69 +/- 6% of maximal CVC) did not affect (P > 0.05) peak CVC compared with control. In part 2, the temperature threshold for the onset of vasodilation was increased by MDF with or without LA treatment and by LA alone (P MDF 36.7 +/- 0.1 degrees C, LA 36.8 +/- 0.1 degrees C, and LA+MDF 36.8 +/- 0.1 degrees C). Peak CVC was decreased by MDF (control 69 +/- 6% of maximal CVC vs. MDF 58 +/- 8% of maximal CVC; P MDF in the presence of LA (73 +/- 12% of maximal CVC) did not affect (P > 0.05) peak CVC compared with control. Thus LA or MDF increases the temperature threshold for the onset of vasodilation. MDF alone decreases the peak vasodilator response in CVC to WBH

  11. 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

  12. 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

  13. 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.

  14. Vascular growth responses to chronic arterial occlusion are unaffected by myeloid specific focal adhesion kinase (FAK) deletion

    Science.gov (United States)

    Heuslein, Joshua L.; Murrell, Kelsey P.; Leiphart, Ryan J.; Llewellyn, Ryan A.; Meisner, Joshua K.; Price, Richard J.

    2016-05-01

    Arteriogenesis, or the lumenal expansion of pre-existing arterioles in the presence of an upstream occlusion, is a fundamental vascular growth response. Though alterations in shear stress stimulate arteriogenesis, the migration of monocytes into the perivascular space surrounding collateral arteries and their differentiation into macrophages is critical for this vascular growth response to occur. Focal adhesion kinase’s (FAK) role in regulating cell migration has recently been expanded to primary macrophages. We therefore investigated the effect of the myeloid-specific conditional deletion of FAK on vascular remodeling in the mouse femoral arterial ligation (FAL) model. Using laser Doppler perfusion imaging, whole mount imaging of vascular casted gracilis muscles, and immunostaining for CD31 in gastrocnemius muscles cross-sections, we found that there were no statistical differences in perfusion recovery, arteriogenesis, or angiogenesis 28 days after FAL. We therefore sought to determine FAK expression in different myeloid cell populations. We found that FAK is expressed at equally low levels in Ly6Chi and Ly6Clo blood monocytes, however expression is increased over 2-fold in bone marrow derived macrophages. Ultimately, these results suggest that FAK is not required for monocyte migration to the perivascular space and that vascular remodeling following arterial occlusion occurs independently of myeloid specific FAK.

  15. Cases of limb-body wall complex: Early amnion rupture, vascular disruption, or abnormal splitting of the embryo?

    Science.gov (United States)

    Crespo, Frank; Pinar, Halit; Kostadinov, Stefan

    2012-12-01

    We report two cases of limb-body wall complex (LBWC), also known as body stalk anomaly, a rare form of body wall defect incompatible with life. The first case was identified during a level II ultrasound examination performed at 7 wk gestational age. The delivery was by breech extraction at 39 wk and 4 days. The second case was delivered by spontaneous vaginal delivery at 35 wk and 5 days. Karyotype analysis was normal in both fetuses. The phenotype of LBWC is variable, but commonly identified features include: exencephaly, limb defects, and either facial clefts or thoraco-abdominoschisis. The exact etiology remains uncertain, as the disorder has been regarded as sporadic with low recurrence. Vascular disruption during early embryogenesis, early amnion rupture, abnormal splitting of the embryo, and failure of amnion fusion have been implicated in the pathogenesis of LBWC. A role for possible gene mutation and maternal use of alcohol, tobacco, or illicit drugs has also been suggested. Detailed ultrasonography along with biochemical screening may allow for early detection.

  16. The early antitumor immune response is necessary for tumor growth

    OpenAIRE

    Parmiani, Giorgio; Maccalli, Cristina

    2012-01-01

    Early events responsible of tumor growth in patients with a normal immune system are poorly understood. Here, we discuss, in the context of human melanoma, the Prehn hypothesis according to which a weak antitumor immune response may be required for tumor growth before weakly or non-immunogenic tumor cell subpopulations are selected by the immune system.

  17. 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 nitroprus

  18. Role of endothelium/nitric oxide in vascular response to flavonoids and epicatechin

    Institute of Scientific and Technical Information of China (English)

    HUANG Yu; YAO Xiao-qiang; TSANG Suk Ying; LAU Chi-Wai; CHEN Zhen-Yu

    2000-01-01

    AIM: To examine the role of endothelium in the vascular responses to flavonoids, baicalein, baicalin, cardamonin, alpinetin, and to purified jasmine green tea (-)epicatechin in the isolated rat mesenteric artery rings. METHODS: The isometric contraction was measured by Grass force-displacement transducers. RESULTS: Both baicalein and baicalin enhanced the phenylephrine-induced contractile response in the endothelium-intact rings. This enhancement was abolished by pretreatment with the nitric oxide inhibitor NG-nitro- L-arginine or in the absence of the endothelium. Both flavonoids also inhibited the acetylcholine-induced endothelial nitric oxide-dependent relaxation. In contrast, cardamonin, alpinetin or (-)epicatechin induced both endothelium-dependent and -independent relaxation. NG-nitro-L-arginine meyhyl ester or endothelium denudation attenuated the endotheliurn-dependent relaxation to the same extent. CONCLUSION: Baicalein and baicalin enhanced the phenylephrine-induced contraction most likely through inhibiting production or/and release of endothelial nitric oxide. Whilst, cardamonin-, alpinetin- or (-)epicatechin-induced endothelium-dependent relaxation is primarily mediated through endothelial nitric oxide.

  19. Suppression of angiotensin II stimulated responses in aortic vascular smooth muscle cells of experimental cirrhotic rats

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    Functional responses to angiotensin II(AT-II) were determined in aortic vascular smooth muscle cells (VSMCs) from experimental cirrhotic rats.Our data showed that AT-II-stimulated extracellular acidification rate (ECAR),which was measured by Cytosesor microphysiometry,was significantly reduced in the aortic VSMCs from the cirrhotic rats as compared to those from the control animals.The ability of AT-II to promote formation of inositol phosphates,the second messenger produced by the activation of Gq-coupled receptors,was also considerably suppressed in the cirrhotic VSMCs.Furthermore,the maximal p42/44 MAPK phosphorylation stimulated by AT-II was significantly reduced in the cirrhotic VSMCs in contrast to that in the normal VSMCs.Taken together,our data clearly demonstrated that the functional responses to AT-II was severely suppressed in aortic VSMCs in cirrhosis,indicating the impairment of general Gq-coupled receptor signaling and subsequent biological function in the cirrhotic VSMCs.

  20. 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

  1. SIRT1 Regulates the Inflammatory Response of Vascular Adventitial Fibroblasts through Autophagy and Related Signaling Pathway.

    Science.gov (United States)

    Wang, Wei-Rong; Li, Ting-Ting; Jing, Ting; Li, Yan-Xiang; Yang, Xiao-Feng; He, Yan-Hao; Zhang, Wei; Lin, Rong; Zhang, Ji-Ye

    2017-01-01

    Autophagy is a lysosomal degradation pathway that is essential for cellular survival, differentiation, and homeostasis. Sirtuin 1 (SIRT1), a NAD+-dependent deacetylase, plays a pivotal role in modulation of autophagy. Recent studies found that autophagy was involved in the regulation of inflammatory response. In this study, we aimed to determine the effect of SIRT1 on autophagy and inflammation, and whether autophagy can regulate the inflammatory response in vascular adventitial fibroblasts (VAFs). Cell autophagy was evaluated by fluorescence microscope and transmission electron microscopy. The expression of protein and mRNA were determined by Western blot analysis and real time-PCR. The production of cytokine was detected by ELISA. TNF-α induced autophagy and increased SIRT1 expression in VAFs. SIRT1 activator resveratrol enhanced TNF-α-induced VAF autophagy. In contrast, SIRT1 knockdown attenuated VAF autophagy. Both the Akt inhibitor MK2206 and mTOR inhibitor rapamycin further increased TNF-α-induced VAF autophagy. Furthermore, SIRT1 knockdown increased Akt phosphorylation and inhibited the autophagy in VAFs. However, MK2206 attenuated the effect of SIRT1 knockdown on VAF autophagy. In addition, ingenuity pathway analysis showed that there is a relationship between cell autophagy and inflammation. We found that SIRT1 knockdown increased the expression of NLRP3 and interleukin (IL)-6 and promoted the production of IL-1β in VAFs. Further study showed that autophagy activation decreased the expression of NLRP3 and IL-6 and inhibited the production of IL-1β, whereas autophagy inhibition increased the inflammatory response of VAFs. More importantly, our study showed that autophagy was involved in the degradation of NLRP3 through the autophagy-lysosome pathway. SIRT1 not only regulates VAF autophagy through the Akt/mTOR signaling pathway but also suppresses the inflammatory response of VAFs through autophagy. © 2017 The Author(s)Published by S. Karger AG, Basel.

  2. Experimental investigation of the early interaction between cyanobacterial soil crusts and vascular plants

    Science.gov (United States)

    Klemens Zaplata, Markus; Veste, Maik; Pohle, Ina; Schümberg, Sabine; Abreu Schonert, Iballa; Hinz, Christoph

    2016-04-01

    While there are hints that biological soil crusts (BSCs) can constitute physical barriers for the emergence of vascular plants, a conceptual approach for the quantitative evaluation of these effects is still missing. Here we present an experimental design to test the emergence of seedlings in situ with (i) capping natural intact, (ii) destroyed and (iii) removed BSC. The selected field site is directly adjacent to the constructed Hühnerwasser catchment (Lusatia, Germany). This site exists since the end of 2008 and consists of loamy sand. Serving as proxy for seedling thrust, we inserted pre-germinated seeds of three confamiliar plant species with different seed masses (members of the Fabaceae family: Lotus corniculatus L., Ornithopus sativus Brot., and Glycine max (L.) Merr.). In each treatment as well as in the control group planting depths were 10 mm. We took care that experimental plots had identical crust thickness, slightly less than 4 mm, serving as proxy for mechanical resistance. A plot became established as follows: Firstly, the pristine crusted surface was vertically cut. To the windward side the BSC remained intact (i: "with BSC" stripe). To the downwind side soil material was temporarily excavated for laterally inserting the seeds beneath the surface of the first stripe. Then at the thereby disturbed second stripe pulverised BSC material became filled as a top layer (ii: "BSC mix" stripe). From the next stripe the BSC was removed (iii: "no BSC" stripe). Thus each plot had each experimental group in spatial contiguity (within 50 cm × 50 cm). The overall 50 plots were distributed across an area of 40 m × 12 m. When individuals of a species either emerged at all stripes, "× × ×", or at no stripe of a plot, "- - -", there was no reason to suppose any effect of a crust. The "- × ×" emergence pattern (depicting the appearance of seedlings in both stripes possessing manipulated surfaces) points towards hindrance more clearly than "- × -" or "- -

  3. Association of Early Atherosclerosis with Vascular Wall Shear Stress in Hypercholesterolemic Zebrafish.

    Directory of Open Access Journals (Sweden)

    Sang Joon Lee

    Full Text Available Although atherosclerosis is a multifactorial disease, the role of hemodynamic information has become more important. Low and oscillating wall shear stress (WSS that changes its direction is associated with the early stage of atherosclerosis. Several in vitro and in vivo models were proposed to reveal the relation between the WSS and the early atherosclerosis. However, these models possess technical limitations in mimicking real physiological conditions and monitoring the developmental course of the early atherosclerosis. In this study, a hypercholesterolaemic zebrafish model is proposed as a novel experimental model to resolve these limitations. Zebrafish larvae are optically transparent, which enables temporal observation of pathological variations under in vivo condition. WSS in blood vessels of 15 days post-fertilisation zebrafish was measured using a micro particle image velocimetry (PIV technique, and spatial distribution of lipid deposition inside the model was quantitatively investigated after feeding high cholesterol diet for 10 days. Lipids were mainly deposited in blood vessel of low WSS. The oscillating WSS was not induced by the blood flows in zebrafish models. The present hypercholesterolaemic zebrafish would be used as a potentially useful model for in vivo study about the effects of low WSS in the early atherosclerosis.

  4. Mitochondrial aldehyde dehydrogenase mediates vasodilator responses of glyceryl trinitrate and sodium nitrite in the pulmonary vascular bed of the rat.

    Science.gov (United States)

    Badejo, Adeleke M; Hodnette, Chris; Dhaliwal, Jasdeep S; Casey, David B; Pankey, Edward; Murthy, Subramanyam N; Nossaman, Bobby D; Hyman, Albert L; Kadowitz, Philip J

    2010-09-01

    It has been reported that mitochondrial aldehyde dehydrogenase (ALDH2) catalyzes the formation of glyceryl dinitrate and inorganic nitrite from glyceryl trinitrate (GTN), leading to an increase in cGMP and vasodilation in the coronary and systemic vascular beds. However, the role of nitric oxide (NO) formed from nitrite in mediating the response to GTN in the pulmonary vascular bed is uncertain. The purpose of the present study was to determine if nitrite plays a role in mediating vasodilator responses to GTN. In this study, intravenous injections of GTN and sodium nitrite decreased pulmonary and systemic arterial pressures and increased cardiac output. The decreases in pulmonary arterial pressure under baseline and elevated tone conditions and decreases in systemic arterial pressure in response to GTN and sodium nitrite were attenuated by cyanamide, an ALDH2 inhibitor, whereas responses to the NO donor, sodium nitroprusside (SNP), were not altered. The decreases in pulmonary and systemic arterial pressure in response to GTN and SNP were not altered by allopurinol, an inhibitor of xanthine oxidoreductase, whereas responses to sodium nitrite were attenuated. GTN was approximately 1,000-fold more potent than sodium nitrite in decreasing pulmonary and systemic arterial pressures. These results suggest that ALDH2 plays an important role in the bioactivation of GTN and nitrite in the pulmonary and systemic vascular beds and that the reduction of nitrite to vasoactive NO does not play an important role in mediating vasodilator responses to GTN in the intact chest rat.

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

    Directory of Open Access Journals (Sweden)

    Célio Damacena-Angelis

    2017-08-01

    Full Text Available 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 (15N-nitrite by aortic rings using ultra-performance liquid chromatography tandem mass-spectrometry (UPLC-MS/MS. Nitrate exerted no effect on aortic accumulation of 15N-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

  6. 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.

  7. SIRT1 inhibits inflammatory response partly through regulation of NLRP3 inflammasome in vascular endothelial cells.

    Science.gov (United States)

    Li, Yanxiang; Wang, Ping; Yang, Xiaofeng; Wang, Weirong; Zhang, Jiye; He, Yanhao; Zhang, Wei; Jing, Ting; Wang, Bo; Lin, Rong

    2016-09-01

    Emerging evidence has indicated that vascular endothelial cells (ECs) not only form the barrier between blood and the vessel wall but also serve as conditional innate immune cells. Our previous study found that SIRT1, a class III histone deacetylase, inhibits the inflammatory response in ECs. Recent studies revealed that SIRT1 also participates in the modulation of immune responses. Although the NLRP3 inflammasome is known to be a crucial component of the innate immune system, there is no direct evidence demonstrating the anti-inflammatory effect of SIRT1 on ECs through the NLRP3 inflammasome. In this study, we observed that lipopolysaccharide (LPS) and adenosine triphosphate (ATP) triggered the activation of NLRP3 inflammasome in human umbilical vein ECs (HUVECs). Moreover, SIRT1 expression was reduced in HUVECs stimulated with LPS and ATP. SIRT1 activator inhibited the expression of monocyte chemotactic protein-1 (MCP-1) and C-reactive protein (CRP), whereas SIRT1 knockdown resulted in significant increases in MCP-1 and CRP levels in HUVECs stimulated with LPS and ATP. Importantly, the lack of SIRT1 enhanced NLRP3 inflammasome activation and subsequent caspase-1 cleavage. On the other hand, NLRP3 siRNA blocked the activation of the NLRP3 inflammasome in HUVECs stimulated with LPS plus ATP. Further study revealed that NLRP3 inflammasome blockade significantly reduced MCP-1 and CRP production in HUVECs. In vivo studies indicated that implantation of the periarterial carotid collar inhibited arterial SIRT1 expression in rabbits. Meanwhile, treatment with a SIRT1 activator decreased the expression levels of MCP-1 and CRP in collared arteries and the interleukin (IL)-1β level in serum. Taken together, these findings indicate that NLRP3 inflammasome activation promoted endothelial inflammation and that SIRT1 inhibits the inflammatory response partly through regulation of the NLRP3 inflammasome in ECs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Experimental investigation on the vascular thermal response to near-infrared laser pulses.

    Science.gov (United States)

    Li, Dong; Chen, Bin; Wu, Wenjuan; Ying, Zhaoxia

    2017-09-02

    Port wine stains (PWS) are congenital vascular malformations that progressively darken and thicken with age. To improve the effect of laser therapy in clinical practice, thermal response of blood vessel to a 1064 nm Nd:YAG laser with controlled energy doses and pulse durations was evaluated using the dorsal skin chamber model. A total of 137 vessels with 30-300 μm diameters were selected from the dorsal skin of the mouse to match those capillaries in port wine stains. Experimental results showed that the thermal response of blood vessels to 1064 nm laser irradiation can be classified as follows: vessel dilation, coagulation, constriction with decreased diameter, complete constriction, hemorrhage, and collagen damage with increasing laser radiant exposure. In most cases, that is, 83 of 137 blood vessels (60.6%), Nd:YAG laser irradiation was characterized by complete constriction (immediate blood vessel disappearance). To reveal the possible damage mechanisms and evaluate blood vessel photocoagulation patterns, theoretical investigation using bioheat transfer equation was conducted in mouse skin with a depth of 1000 μm. Complete constriction as the dominant thermal response as evidenced by uniform blood heating within the vessel lumen was noted in both experimental observation and theoretical investigation. To achieve the ideal clinical effect using the Nd:YAG laser treatment, the radiant exposure should not only be high enough to induce complete constriction of the blood vessels but also controlled carefully to avoid surrounding collagen damage. The short pulse duration of 1-3 ms is better than long pulse durations because hemorrhaging of small capillaries is occasionally observed postirradiation with pulse durations longer than 10 ms.

  9. Let-7e modulates the inflammatory response in vascular endothelial cells through ceRNA crosstalk

    Science.gov (United States)

    Lin, Zongwei; Ge, Junfeng; Wang, Zhe; Ren, Jianwei; Wang, Xiaowei; Xiong, Hui; Gao, Jing; Zhang, Yan; Zhang, Qunye

    2017-01-01

    The inflammatory responses of vascular endothelial cells (VECs) are critical in the development of many cardio-cerebrovascular diseases. Let-7e is an important regulator of endothelial function and inflammation. However, the effects and mechanisms of let-7e on VECs inflammation have not been studied until recently. Thus, we investigated these issues and found that in addition to proliferation, apoptosis and cell adhesion, let-7e was also implicated in the regulation of inflammatory responses through a complex network, including IκBβ and lncRNA lnc-MKI67IP-3. Let-7e promoted NF-κB activation and translocation to the nucleus by inhibiting its target gene (IκBβ) expression and subsequently increased the expression of inflammatory and adhesion molecules. Meanwhile, lnc-MKI67IP-3 acted as a sponge or competing endogenous RNA (ceRNA) for let-7e, suppressing its pro-inflammatory effects, and let-7e decreased lnc-MKI67IP-3 expression, thereby forming a positive feedback loop to aggravate inflammation. Moreover, let-7e, lnc-MKI67IP-3 and IκBβ were also abnormal in oxLDL-treated VECs and atherosclerotic plaques. The present study revealed let-7e as a pro-inflammatory mediator and a novel regulatory mechanism for the NF-κB pathway through ceRNA crosstalk, comprising let-7e and its target IκBβ and the ceRNA lnc-MKI67IP-3. Thus, this molecule might play important roles in the inflammatory responses of VECs and development of atherosclerosis. PMID:28195197

  10. 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....

  11. 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.)

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

    Energy Technology Data Exchange (ETDEWEB)

    Latham, Antony M.; Odell, Adam F. [Endothelial Cell Biology Unit, School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT (United Kingdom); Mughal, Nadeem A. [Leeds Vascular Institute, Leeds General Infirmary, Great George Street, Leeds LS1 3EX (United Kingdom); Issitt, Theo; Ulyatt, Clare; Walker, John H. [Endothelial Cell Biology Unit, School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT (United Kingdom); Homer-Vanniasinkam, Shervanthi [Leeds Vascular Institute, Leeds General Infirmary, Great George Street, Leeds LS1 3EX (United Kingdom); Ponnambalam, Sreenivasan, E-mail: s.ponnambalam@leeds.ac.uk [Endothelial Cell Biology Unit, School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT (United Kingdom)

    2012-11-01

    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: Black-Right-Pointing-Pointer Endothelial cells mount a stress response under conditions of low serum. Black

  13. Cardiac and Vascular Responses to Thigh Cuffs and Respiratory Maneuvers on Crewmembers of the International Space Station

    Science.gov (United States)

    Hamilton, Douglas; Sargsyan, Ashot E.; Garcia, Kathleen; Ebert, Douglas; Whitson, Peggy A.; Feiveson, Alan; Alferova, Irina V.; Dulchavsky, Scott A.; Matveev, Vladimir P.; Bogomolov, Valery V.; hide

    2011-01-01

    The transition to microgravity eliminates the hydrostatic gradients in the vascular system. The resulting fluid redistribution commonly manifests as facial edema, engorgement of the external neck veins, and a decrease in leg diameter. This experiment examined the responses to modified Valsalva and Mueller maneuvers measured by cardiac and vascular ultrasound (ECHO) in a baseline steady state and during preload reduction introduced with thigh occlusion cuffs used as a counter-measure device (Braslet cuffs) measured by cardiac and vascular ultrasound examinations. Methods: Nine International Space Station crewmember subjects (Expeditions 16 - 20) were examined in 15 experiment sessions 101 +/- 46.days after launch (mean +/- SD; 33 - 185). Twenty Seven cardiac and vascular parameters were obtained with/without respiratory maneuvers before and after tightening of the Braslet cuffs. Results: Non-physicians performed diagnostic-quality cardiac and vascular ultrasound examinations using remote guidance. Three of 27 combinations of maneuvers and Braslet or Braslet alone were identified as being significant changed when compared to baseline. Eleven of 81 differences between combinations of Mueller, Valsalva or baseline were significant and related to cardiac preload reduction or increase in lower extremity venous volume. Conclusions: Acute application of Braslet occlusion cuffs causes lower extremity fluid sequestration and exerts commensurate measurable effects on cardiac performance in microgravity. Ultrasound techniques to measure the hemodynamic effects of thigh cuffs in combination with respiratory maneuvers may serve as an invaluable tool in determining the volume status of the cardiac patient at the 'microgravity bedside'.

  14. Tyrosine Phosphorylation Modulates the Vascular Responses of Mesenteric Arteries from Human Colorectal Tumors

    Directory of Open Access Journals (Sweden)

    Eduardo Ferrero

    2013-01-01

    Full Text Available The aim of this study was to analyze whether tyrosine phosphorylation in tumoral arteries may modulate their vascular response. To do this, mesenteric arteries supplying blood flow to colorectal tumors or to normal intestine were obtained during surgery and prepared for isometric tension recording in an organ bath. Increasing tyrosine phosphorylation with the phosphatase inhibitor, sodium orthovanadate produced arterial contraction which was lower in tumoral than in control arteries, whereas it reduced the contraction to noradrenaline in tumoral but not in control arteries and reduced the relaxation to bradykinin in control but not in tumoral arteries. Protein expression of VEGF-A and of the VEGF receptor FLT1 was similar in control and tumoral arteries, but expression of the VEGF receptor KDR was increased in tumoral compared with control arteries. This suggests that tyrosine phosphorylation may produce inhibition of the contraction in tumoral mesenteric arteries, which may increase blood flow to the tumor when tyrosine phosphorylation is increased by stimulation of VEGF receptors.

  15. Microarray Analysis of Human Vascular Smooth Muscle Cell Responses to Bacterial Lipopolysaccharide

    Directory of Open Access Journals (Sweden)

    Joe Minta

    2007-01-01

    Full Text Available Accumulating evidence suggest a causal role of bacterial and viral infections in atherogenesis. Bacterial lipopolysaccharide (LPS has been shown to stimulate resting vascular smooth muscle cells (SMC with the production of inflammatory cytokines and modulation of quiescent cells to the proliferative and synthetic phenotype. To comprehensively identify biologically important genes associated with LPS-induced SMC phenotype modulation, we compared the transcriptomes of quiescent human coronary artery SMC and cells treated with LPS for 4 and 22 h. The SMCs responded robustly to LPS treatment by the differential regulation of several genes involved in chromatin remodeling, transcription regulation, translation, signal transduction, metabolism, host defense, cell proliferation, apoptosis, matrix formation, adhesion and motility and suggest that the induction of clusters of genes involved in cell proliferation, migration and ECM production may be the main force that drives the LPS-induced phenotypic modulation of SMC rather than the differential expression of a single gene or a few genes. An interesting observation was the early and dramatic induction of four tightly clustered interferon-induced genes with tetratricopeptide repeats (IFIT1, 2, 4, 5. siRNA knock-down of IFIT1 in SMC was found to be associated with a remarkable up-regulation of TP53, CDKN1A and FOS, suggesting that IFIT1 may play a role in cell proliferation. Our data provide a comprehensive list of genes involved in LPS biology and underscore the important role of LPS in SMC activation and phenotype modulation which is a pivotal event in the onset of atherogenesis.

  16. The highest-copy repeats are methylated in the small genome of the early divergent vascular plant Selaginella moellendorffii

    Directory of Open Access Journals (Sweden)

    Quan Hui

    2008-06-01

    Full Text Available Abstract Background The lycophyte Selaginella moellendorffii is a vascular plant that diverged from the fern/seed plant lineage at least 400 million years ago. Although genomic information for S. moellendorffii is starting to be produced, little is known about basic aspects of its molecular biology. In order to provide the first glimpse to the epigenetic landscape of this early divergent vascular plant, we used the methylation filtration technique. Methylation filtration genomic libraries select unmethylated DNA clones due to the presence of the methylation-dependent restriction endonuclease McrBC in the bacterial host. Results We conducted a characterization of the DNA methylation patterns of the S. moellendorffii genome by sequencing a set of S. moellendorffii shotgun genomic clones, along with a set of methylation filtered clones. Chloroplast DNA, which is typically unmethylated, was enriched in the filtered library relative to the shotgun library, showing that there is DNA methylation in the extremely small S. moellendorffii genome. The filtered library also showed enrichment in expressed and gene-like sequences, while the highest-copy repeats were largely under-represented in this library. These results show that genes and repeats are differentially methylated in the S. moellendorffii genome, as occurs in other plants studied. Conclusion Our results shed light on the genome methylation pattern in a member of a relatively unexplored plant lineage. The DNA methylation data reported here will help understanding the involvement of this epigenetic mark in fundamental biological processes, as well as the evolutionary aspects of epigenetics in land plants.

  17. Early diagenesis of vascular plant tissues: Lignin and cutin decomposition and biogeochemical implications

    Science.gov (United States)

    Opsahl, Stephen; Benner, Ronald

    1995-12-01

    Long-term subaqueous decomposition patterns of five different vascular plant tissues including mangrove leaves and wood ( Avicennia germinans), cypress needles and wood ( Taxodium distichum) and smooth cordgrass ( Spartina alternifora) were followed for a period of 4.0 years, representing the longest litter bag decomposition study to date. All tissues decomposed under identical conditions and final mass losses were 97, 68, 86, 39, and 93%, respectively. Analysis of the lignin component of herbaceous tissues using alkaline CuO oxidation was complicated by the presence of a substantial ester-bound phenol component composed primarily of cinnamyl phenols. To overcome this problem, we introduce a new parameter to represent lignin, Λ6. Λ6 is comprised only of the six syringyl and vanillyl phenols and was found to be much less sensitive to diagenetic variation than the commonly used parameter Λ, which includes the cinnamyl phenols. Patterns of change in lignin content were strongly dependent on tissue type, ranging from 77% enrichment in smooth cordgrass to 6% depletion in cypress needles. In contrast, depletion of cutin was extensive (65-99%) in all herbaceous tissues. Despite these differences in the overall reactivity of lignin and cutin, both macromolecules were extensively degraded during the decomposition period. The long-term decomposition series also provided very useful information about the compositional parameters which are derived from the specific oxidation products of both lignin and cutin. The relative lability of ester-bound cinnamyl phenols compromised their use in parameters to distinguish woody from herbaceous plant debris. The dimer to monomer ratios of lignin-derived phenols indicated that most intermonomeric linkages in lignin degraded at similar rates. Acid to aldehyde ratios of vanillyl and syringyl phenols became elevated, particularly during the latter stages of decomposition supporting the use of these parameters as indicators of diagenetic

  18. Neurobehavioral manifestation in early period of Alzheimer Disease and Vascular Dementia

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    Bidzan, Mariola

    2014-04-01

    Full Text Available Introduction: AD and VD are preceded by a preclinical stage. Small but tangible cognitive impairments sometimes occur many years before the onset and diagnosis of dementia. The ongoing degenerative process can be conductive to behavioural and psychological symptoms. Aim: The aim of the study was to investigate the rates of neurobehavioral symptoms in the preclinical stages of AD and VD. Methods: Two hundred and ninety one residents of nursery homes were included in the study. Participants of the study did not display symptoms of dementia in accordance with DSM IV criteria and obtained at least 24 points on the MMSE scale and were on the first or second level of the Global Deterioration Scale. Participants were screened for behavioural and psychological symptoms with the NPI – NH scale, while their cognitive functioning was evaluated by means of the ADAS-cog. Participants of the study were evaluated with the MMSE scale annually. Participants who obtained less than 24 points on the MMSE scale were evaluated by a senior psychiatrist. Diagnosis of dementia was done on the basis of DSM criteria. Alzheimer’s Disease was diagnosed on the basis of NINCDS-ADRDA criteria and vascular dementia on the NINDS-AIREN criteria. The study was carried out over a period of seven consecutive years. Results: A hundred and fifty people were included in the final analysis – in 111 of them were found not to be afflicted with dementia, 25 were found to have AD and in 14 VD was diagnosed. The control group differed from the AD and VD group with respect to the initial level of cognitive impairment (ADAS-cog and the intensity of behavioural and psychological symptoms (NPI –NH scale. Particular items of the NPI –NH scale differentiated the two groups to a different degree. In people with AD the greatest differences were observed with respect to agitation/aggression, mood swings, irritability/emotional liability and the rates of anxiety. People with VD, similarly to

  19. 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.

  20. Maternal iron status in early pregnancy and birth outcomes: insights from the Baby's Vascular health and Iron in Pregnancy study.

    Science.gov (United States)

    Alwan, Nisreen A; Cade, Janet E; McArdle, Harry J; Greenwood, Darren C; Hayes, Helen E; Simpson, Nigel A B

    2015-06-28

    Fe deficiency anaemia during early pregnancy has been linked with low birth weight and preterm birth. However, this evidence comes mostly from studies measuring Hb levels rather than specific measures of Fe deficiency. The present study aimed to examine the association between maternal Fe status during the first trimester of pregnancy, as assessed by serum ferritin, transferrin receptor and their ratio, with size at birth and preterm birth. In the Baby VIP (Baby's Vascular health and Iron in Pregnancy) study, we recruited 362 infants and their mothers after delivery in Leeds, UK. Biomarkers were measured in maternal serum samples previously obtained in the first trimester of pregnancy. The cohort included sixty-four (18 %) small for gestational age (SGA) babies. Thirty-three babies were born preterm (9 %; between 34 and 37 weeks). First trimester maternal Fe depletion was associated with a higher risk of SGA (adjusted OR 2·2, 95 % CI 1·1, 4·1). This relationship was attenuated when including early pregnancy Hb in the model, suggesting it as a mediator (adjusted OR 1·6, 95 % CI 0·8, 3·2). For every 10 g/l increase in maternal Hb level in the first half of pregnancy the risk of SGA was reduced by 30 % (adjusted 95 % CI 0, 40 %); levels below 110 g/l were associated with a 3-fold increase in the risk of SGA (95 % CI 1·0, 9·0). There was no evidence of association between maternal Fe depletion and preterm birth (adjusted OR 1·5, 95 % 0·6, 3·8). The present study shows that depleted Fe stores in early pregnancy are associated with higher risk of SGA.

  1. 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)

    Swartley, Olivia M; Foley, Julie F; Livingston, David P; Cullen, John M; Elmore, Susan A

    2016-07-01

    A critical event in embryo development is the proper formation of the vascular system, of which the hepatobiliary system plays a pivotal role. This has led researchers to use transgenic mice to identify the critical steps involved in developmental disorders associated with the hepatobiliary vascular system. Vascular development is dependent upon normal vasculogenesis, angiogenesis, and the transformation of vessels into their adult counterparts. Any alteration in vascular development has the potential to cause deformities or embryonic death. Numerous publications describe specific stages of vascular development relating to various organs, but a single resource detailing the stage-by-stage development of the vasculature pertaining to the hepatobiliary system has not been available. This comprehensive histology atlas provides hematoxylin & eosin and immunohistochemical-stained sections of the developing mouse blood and lymphatic vasculature with emphasis on the hepatobiliary system between embryonic days (E) 11.5-18.5 and the early postnatal period. Additionally, this atlas includes a 3-dimensional video representation of the E18.5 mouse venous vasculature. One of the most noteworthy findings of this atlas is the identification of the portal sinus within the mouse, which has been erroneously misinterpreted as the ductus venosus in previous publications. Although the primary purpose of this atlas is to identify normal hepatobiliary vascular development, potential embryonic abnormalities are also described. © The Author(s) 2016.

  2. 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.

  3. Neural stimulation does not mediate attenuated vascular response in ACL-deficient knees: potential role of local inflammatory mediators.

    Science.gov (United States)

    Miller, Daniel; Salo, Paul; Hart, David A; Leonard, Catherine; Mammoto, Takeo; Bray, Robert C

    2010-01-01

    Chronic inflammation associated with osteoarthritis (OA) alters normal responses and modifies the functionality of the articular vasculature. Altered responsiveness of the vasculature may be due to excessive neural activity associated with chronic pain and inflammation, or from the production of inflammatory mediators which induce vasodilation. Using laser speckle perfusion imaging (LSPI), blood flow to the medial collateral ligament (MCL) of adult rabbits was measured in denervated ACL transected knees (n = 6) and compared to unoperated control (n = 6) and 6-week anterial cruciate ligament (ACL)-transected knees (n = 6). Phenylephrine and neuropeptide Y were applied to the MCL vasculature in topical boluses of 100 microL (dose range 10(-14) to 10(-8) mol and 10(-14) to 10(-9) mol, respectively). Denervation diminished vasoconstrictive responsiveness to phenylephrine compared to both control and ACL-transected knees. Denervation minimally enhanced vascular responses to neuropeptide Y (NPY) compared to ACL deficiency alone, which nevertheless remained significantly diminished from control responses. To evaluate the potential role of inflammatory dilators in the diminished contractile responses, phenylephrine was coadministered with histamine, substance P, and prostaglandin E(2). High-dose histamine, and low-dose substance P and PGE(2) were able to inhibit contractile responses in the MCL of control knees. Excessive neural input does not mediate diminished vasoconstrictive responses in the ACL transected knee; inflammatory mediators may play a role in the deficient vascular responsiveness of the ACL transected knee.

  4. Gene expression profiles of mouse aorta and cultured vascular smooth muscle cells differ widely, yet show common responses to dioxin exposure.

    Science.gov (United States)

    Puga, Alvaro; Sartor, Maureen A; Huang, Ming-Ya; Kerzee, J Kevin; Wei, Yu-Dan; Tomlinson, Craig R; Baxter, C Stuart; Medvedovic, Mario

    2004-01-01

    Exposure to environmental toxicants may play a role in the onset and progression of cardiovascular disease. Many environmental agents, such as dioxin, are risk factors for atherosclerosis because they may exacerbate an underlying disease by altering gene expression patterns. Expression profiling of vascular tissues allows the simultaneous analysis of thousands of genes and may provide predictive information particularly useful in early disease stages. Often, however, in vivo experiments are unfeasible for material or ethical reasons, and data from cultured cells must be used instead, even though it may not be known whether cultured cells and live tissues share common global responses to the same toxicant. In a search for genes responsive to dioxin exposure, we used oligonucleotide microarrays with DNA sequences from 13,433 genes to compare global gene expression profiles of C57BL/6 mice aortas with cultured vascular smooth muscle cells (vSMCs) of the same mice. Aorta segments and vSMCs differed in the expression of more than 4500 genes, many showing expression differences greater than 1000-fold. Integration of microarray data into Gene Ontology Project annotations showed that many of the genes differentially expressed belonged to the same biological process or metabolic pathway. Notwithstanding these results, a subset of 35 genes responded in the same fashion to dioxin exposure in both systems. Genes in this subset encoded phase I and phase II detoxification enzymes, signal transduction kinases and phosphatases, and proteins involved in DNA repair and the cell cycle. We conclude that vSMCS may be useful aorta surrogates to study early gene expression responses to dioxin exposure, provided that analyses focus on this subset of genes.

  5. Comparison of the Thickness of the Lamina Cribrosa and Vascular Factors in Early Normal-tension Glaucoma with Low and High Intraocular Pressures

    OpenAIRE

    Kim, Jee Hyun; Lee, Tae Yoon; Lee, Jong Wook; Lee, Kyoo Won

    2014-01-01

    Purpose To compare the thickness of the lamina cribrosa (LC) and vascular factors of early normal-tension glaucoma (NTG) patients with high and low intraocular pressure (IOP) that are expected to be associated with the development of glaucoma. Methods Seventy-one Korean NTG patients with low IOP (the highest IOP 15 mmHg, 31 patients) were included in this study. The thickness of LC and vascular factors were compared. The thickness of the LC was measured using the enhanced depth imaging method...

  6. Age-related differences in memory-encoding fMRI responses after accounting for decline in vascular reactivity.

    Science.gov (United States)

    Liu, Peiying; Hebrank, Andrew C; Rodrigue, Karen M; Kennedy, Kristen M; Section, Jarren; Park, Denise C; Lu, Hanzhang

    2013-09-01

    BOLD fMRI has provided a wealth of information about the aging brain. A common finding is that posterior regions of the brain manifest an age-related decrease in activation while the anterior regions show an age-related increase. Several neurocognitive models have been proposed to interpret these findings. However, one issue that has not been sufficiently considered to date is that the BOLD signal is based on vascular responses secondary to neural activity. Thus the above findings could be in part due to a vascular change, especially in view of the expected decline of vascular health with age. In the present study, we aim to examine age-related differences in memory-encoding fMRI response in the context of vascular aging. One hundred and thirty healthy subjects ranging from 20 to 89 years old underwent a scene-viewing fMRI task and, in the same session, cerebrovascular reactivity (CVR) was measured in each subject using a CO2-inhalation task. Without accounting for the influence of vascular changes, the task-activated fMRI signal showed the typical age-related decrease in visual cortex and medial temporal lobe (MTL), but manifested an increase in the right inferior frontal gyrus (IFG). In the same individuals, an age-related CVR reduction was observed in all of these regions. We then used a previously proposed normalization approach to calculate a CVR-corrected fMRI signal, which was defined as the uncorrected signal divided by CVR. Based on the CVR-corrected fMRI signal, an age-related increase is now seen in both the left and right sides of IFG; and no brain regions showed a signal decrease with age. We additionally used a model-based approach to examine the fMRI data in the context of CVR, which again suggested an age-related change in the two frontal regions, but not in the visual and MTL regions.

  7. Role of vascular density and normalization in response to neoadjuvant bevacizumab and chemotherapy in breast cancer patients

    OpenAIRE

    Tolaney, Sara M.; Boucher, Yves; Duda, Dan G.; Martin, John D.; Seano, Giorgio; Ancukiewicz, Marek; Barry, William T.; Goel, Shom; Lahdenrata, Johanna; Isakoff, Steven J.; Yeh, Eren D.; Jain, Saloni R.; Golshan, Mehra; Brock, Jane; Snuderl, Matija

    2015-01-01

    Emerging evidence indicates patients who benefit from antiangiogenic therapies have improved vessel function. To determine how bevacizumab modulates vessel morphology to improve vessel function we conducted a phase II trial of preoperative bevacizumab followed by bevacizumab combined with chemotherapy in HER2-negative breast cancer patients. Our results suggest that the clinical response to bevacizumab may occur through an increase in the extent of vascular normalization primarily in patients...

  8. Critical Role of Striatin in Blood Pressure and Vascular Responses to Dietary Sodium Intake.

    Science.gov (United States)

    Garza, Amanda E; Pojoga, Luminita H; Moize, Burhanuddin; Hafiz, Wan M; Opsasnick, Lauren A; Siddiqui, Waleed T; Horenstein, Michael; Adler, Gail K; Williams, Gordon H; Khalil, Raouf A

    2015-09-01

    Striatin is a protein regulator of vesicular trafficking in neurons that also binds caveolin-1 and Ca(2+)-calmodulin and could activate endothelial nitric oxide synthase. We have shown that striatin colocalizes with the mineralocorticoid receptor and that mineralocorticoid receptor activation increases striatin levels in vascular cells. To test whether striatin is a regulator of vascular function, wild-type and heterozygous striatin-deficient mice (Strn(+/-)) were randomized in crossover intervention to restricted (0.03%) and liberal sodium (1.6%) diets for 7 days on each diet, and blood pressure and aortic vascular function were measured. Compared with wild-type, sodium restriction significantly reduced blood pressure in Strn(+/-). On liberal salt intake, phenylephrine and high KCl caused a greater vascular contraction in Strn(+/-) than wild-type, and endothelium removal, nitric oxide synthase inhibitor L-NAME, and guanylate cyclase inhibitor ODQ enhanced phenylephrine contraction to a smaller extent in Strn(+/-) than wild-type. On liberal salt, acetylcholine relaxation was less in Strn(+/-) than in wild-type, and endothelium removal, L-NAME, and ODQ blocked acetylcholine relaxation, suggesting changes in endothelial NO-cGMP. On liberal salt, endothelial nitric oxide synthase mRNA expression and the ratio of endothelial nitric oxide synthase activator pAkt/total Akt were decreased in Strn(+/-) versus wild-type. Vascular relaxation to NO donor sodium nitroprusside was not different among groups. Thus, striatin deficiency is associated with salt sensitivity of blood pressure, enhanced vasoconstriction, and decreased vascular relaxation, suggesting a critical role for striatin, through modulation of endothelial NO-cGMP, in regulation of vascular function and BP during changes in sodium intake.

  9. Safety and efficacy of electrospun polycarbonate-urethane vascular graft for early hemodialysis access: first clinical results in man.

    Science.gov (United States)

    Wijeyaratne, Serosha M; Kannangara, Lushanthi

    2011-01-01

    The purpose of this study was to assess the safety and efficacy of an electrospun multilayered, self-sealing polycarbonate-urethane graft for early hemodialysis access in patients. Seventeen eligible consenting patients had a polycarbonate-urethane graft (AVflo™) implanted and followed up prospectively for 12 months or to the end of secondary patency. Performance measures included graft patency, complications, time to first cannulation, and hemostasis times after needle withdrawal. All patients were of Asian origin (mean age 57 years, range 29-78). Diabetes mellitus was the most common cause of renal failure (52.9%). There were no systemic or local reactions to the graft. Five patients (29.4%) died due to medical complications unrelated to the device. There was 1 pseudoaneurysm, 3 infected grafts that subsequently thrombosed, and 1 primary thrombosis associated with thrombophilia. One venous stenosis needed balloon angioplasty. Primary and secondary patency rates at 6 months were 72.7% and 81.8%, and at 12 months, 54.5% and 72.7%, respectively. Postimplantation vascular access needs were met entirely by the graft in every instance and prevented the need for venous catheters. Fifty-six percent were accessed within 8 days, the earliest being 48 hours. Finally, all arterial punctures and 98% of venous punctures had sealed in less than 5 minutes, with two thirds sealing off within 3 minutes of needle withdrawal. The electrospun polycarbonate-urethane graft is safe in humans, permits early access obviating the need for venous catheters, and has equivalent patency to other prosthetic grafts at 1 year.

  10. Crucial role of Toll-like receptors in the zinc/nickel-induced inflammatory response in vascular endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Tsou, Tsui-Chun, E-mail: tctsou@nhri.org.tw [Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Miaoli 350, Taiwan (China); Liou, Saou-Hsing; Yeh, Szu-Ching; Tsai, Feng-Yuan [Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Miaoli 350, Taiwan (China); Chao, How-Ran [Emerging Compounds Research Center, Department of Environmental Science and Engineering, National Pingtung University and Science and Technology, Neipu, Pingtung 912, Taiwan (China)

    2013-12-15

    Our previous studies indicated that zinc induced inflammatory response in both vascular endothelial cells and promonocytes. Here, we asked if other metals could cause the similar effect on vascular endothelial cells and tried to determine its underlying mechanism. Following screening of fifteen metals, zinc and nickel were identified with a marked proinflammatory effect, as determined by ICAM-1 and IL-8 induction, on human umbilical vein endothelial cells (HUVECs). Inhibiting protein expression of myeloid differentiation primary response protein-88 (MyD88), a Toll-like receptor (TLR) adaptor acting as a TLR-signaling transducer, significantly attenuated the zinc/nickel-induced inflammatory response, suggesting the critical roles of TLRs in the inflammatory response. Blockage of TLR-4 signaling by CLI-095, a TLR-4 inhibitor, completely inhibited the nickel-induced ICAM-1 and IL-8 expression and NFκB activation. The same CLI-095 treatment significantly blocked the zinc-induced IL-8 expression, however with no significant effect on the ICAM-1 expression and a minor inhibitory effect on the NFκB activation. The finding demonstrated the differential role of TLR-4 in regulation of the zinc/nickel-induced inflammatory response, where TLR-4 played a dominant role in NFκB activation by nickel, but not by zinc. Moreover, inhibition of NFκB by adenovirus-mediated IκBα expression and Bay 11-7025, an inhibitor of cytokine-induced IκB-α phosphorylation, significantly attenuated the zinc/nickel-induced inflammatory responses, indicating the critical of NFκB in the process. The study demonstrates the crucial role of TLRs in the zinc/nickel-induced inflammatory response in vascular endothelial cells and herein deciphers a potential important difference in NFκB activation via TLRs. The study provides a molecular basis for linkage between zinc/nickel exposure and pathogenesis of the metal-related inflammatory vascular disease. - Highlights: • Both zinc and nickel cause

  11. Salvianolic acid B inhibits platelets-mediated inflammatory response in vascular endothelial cells.

    Science.gov (United States)

    Xu, Shixin; Zhong, Aiqin; Bu, Xiaokun; Ma, Huining; Li, Wei; Xu, Xiaomin; Zhang, Junping

    2015-01-01

    Salvianolic acid B (SAB) is a hydrophilic component isolated from the Chinese herb Salviae miltiorrhizae, which has been used clinically for the treatment of ischemic cardiovascular and cerebrovascular diseases. Platelets-mediated vascular inflammatory response contributes to the initiation and progression of atherosclerosis. In this paper, we focus on the modulating effects of SAB on the inflammatory reaction of endothelial cells triggered by activated platelets. Human umbilical vein endothelial cells (EA.hy926) were pretreated with SAB followed by co-culture with ADP-activated platelets. Adhesion of platelets to endothelial cells was observed by amorphological method. The activation of nuclear factor-kappa B was evaluated by NF-κB p65 nuclear translocation and the protein phosphorylation. A determination of the pro-inflammatory mediators (ICAM-1, IL-1β, IL-6, IL-8, MCP-1) mRNA and protein were also conducted. In addition, the inhibitory effects of SAB on platelets activation were also evaluated using a platelet aggregation assay and assessing the release level of soluble P-selectin. The results showed that SAB dose-dependently inhibited ADP- or α-thrombin-induced human platelets aggregation in platelet rich plasma (PRP) samples, and significantly decreased soluble P-selectin release from both agonists stimulated washed platelets. It was also found that pre-treatment with SAB reduced adhesion of ADP-activated platelets to EA.hy926 cells and inhibited NF-κB activation. In addition, SAB significantly suppressed pro-inflammatory mediators mRNA and protein in EA.hy926 cells in a dose-dependent manner. These results indicated that, in addition to its inhibitory effects on platelets activation, SAB was able to attenuate platelets-mediated inflammatory responses in endothelial cells even if the platelets had already been activated. This anti-inflammatory effect was related to the inhibition of NF-κB activation. Our findings suggest that SAB may be a potential

  12. Alteration of Leukocyte Count Correlates With Increased Pulmonary Vascular Permeability and Decreased PaO2:FiO2 Ratio Early After Major Burns.

    Science.gov (United States)

    Johansson, Joakim; Steinvall, Ingrid; Herwald, Heiko; Lindbom, Lennart; Sjöberg, Folke

    2015-01-01

    Leukocytes are activated systemically and their numbers increase soon after a burn followed by a rapid decline to low normal or subnormal levels, possibly by increased extravasation. Experimental data support that an important target for such extravasation is the lungs and that leukocytes when they adhere to endothelial cells cause an increase in vascular permeability. The authors investigated a possible relation between early increased pulmonary vascular permeability or a decreased PaO2:FiO2 ratio and the dynamic change in concentration of blood leukocytes after a burn. This is a prospective, exploratory, single-center study. The authors measured the dynamic changes of leukocytes in blood starting early after the burn, pulmonary vascular permeability index by thermodilution, and PaO2:FiO2-ratios in 20 patients during the first 21 days after a major burn (>20% TBSA%). Median TBSA was 40% interquartile range (IQR, 25-52) and full thickness burn 28% (IQR, 2-39). There was a correlation between the early (PaO2:FiO2 < 27 kPa (P = .004). The authors have documented a correlation between dynamic change of blood leukocytes and pulmonary failure early after burns.

  13. 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 durin...... surgery and oral melatonin treatment for 3 days after surgery on biochemical markers of oxidative and inflammatory stress.......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...

  14. Vascular Cures

    Science.gov (United States)

    ... Contact Us Vascular Disease What is Vascular Disease? Education and Awareness Vascular Diseases Abdominal Aortic Aneurysm Aortic Dissection Arteriovenous Malformation Atherosclerosis Buerger's Disease Carotid Artery Disease ...

  15. 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

    OBJECTIVE: To investigate whether signs of chronic compartment syndrome could be found in plantar muscles of falanga torture victims with painful feet and impaired gait. The hypothesis was that the muscular vascular response to two minutes ischemia would be decreased in torture victims compared......, the second was higher and the third was highest indicating that the response to ischemia was disappearing as measurements were made. There was a trend that the first RI was higher in torture victims than in controls. DISCUSSION: The study was not able to confirm the presence of chronic compartment syndrome...

  16. Branding of vascular surgery.

    Science.gov (United States)

    Perler, Bruce A

    2008-03-01

    The Society for Vascular Surgery surveyed primary care physicians (PCPs) to understand how PCPs make referral decisions for their patients with peripheral vascular disease. Responses were received from 250 PCPs in 44 states. More than 80% of the respondents characterized their experiences with vascular surgeons as positive or very positive. PCPs perceive that vascular surgeons perform "invasive" procedures and refer patients with the most severe vascular disease to vascular surgeons but were more than twice as likely to refer patients to cardiologists, believing they are better able to perform minimally invasive procedures. Nevertheless, PCPs are receptive to the notion of increasing referrals to vascular surgeons. A successful branding campaign will require considerable education of referring physicians about the totality of traditional vascular and endovascular care increasingly provided by the contemporary vascular surgical practice and will be most effective at the local grassroots level.

  17. Implementation of responsiveness to intervention in early education settings.

    Science.gov (United States)

    Justice, Laura M; McGinty, Anita; Guo, Ying; Moore, Douglas

    2009-05-01

    This article provides an overview of how response to intervention (RTI) may be used effectively within early childhood settings. Discussion is organized to address such issues regarding RTI implementation as (1) how to design and implement a high-quality Tier 1 learning environment that systematically improves children's language and literacy outcomes, (2) how to design and implement a high-quality Tier 2 supplemental learning intervention that systematically improves the language and literacy outcomes of children who are unresponsive to Tier 1, and (3) how to design and implement a comprehensive and cohesive assessment system that appropriately identifies children who show inadequate response to the Tier 1 and Tier 2 learning opportunities. A model for implementing RTI using the supplemental curriculum by Justice and McGinty, READ IT AGAIN-PREK! (2008), is presented. This tool was developed to meet the needs of early childhood programs as they seek to implement RIA in a cost-effective and scalable manner.

  18. Vascular biomarkers to predict response to exercise in Alzheimer's disease: the study protocol

    Science.gov (United States)

    Li, Danni; Thomas, Robin; Tsai, Michael Y; Li, Ling; Vock, David M; Greimel, Susan; Yu, Fang

    2016-01-01

    Introduction Exercise interventions are a promising treatment for improving cognition in persons with Alzheimer's disease. This is similar to Alzheimer's disease pharmacotherapies in which only 18–48% of treated patients demonstrate improvement in cognition. Aerobic exercise interventions positively affect brain structure and function through biologically sound pathways. However, an under-studied mechanism of aerobic exercise's effects is n-3 fatty acids in plasma. The objective of this pilot study is to inform a future large-scale study to develop n-3 fatty acids-based prediction of cognitive responses to aerobic exercise treatment in Alzheimer's disease. Methods and analysis This study will recruit and follow a cohort of 25 subjects enrolled in the FIT-AD Trial, an ongoing randomised controlled trial that investigates the effects of a 6-month moderate-intensity cycling intervention on cognition and hippocampal volume in older adults with mild to moderate Alzheimer's disease over a year. This study will collect blood from subjects at baseline and at 3 and 6 months to assay vascular biomarkers (ie, plasma fatty acids). Global cognition as measured by the Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog) at baseline, 3, 6, 9 and 12 months will be used as the main outcome. A multiple linear-regression model will be used with 12-month change in cognition as the outcome and baseline measure of n-3 fatty acids or changes in the ratio of n-3 to n-6 fatty-acid levels in plasma at 3 and/or 6 months, randomised treatment group, and their interaction as predictors. Ethics and dissemination We have obtained Institutional Review Board approval for our study. We obtain consent or assent/surrogate consent from all subjects depending on their consenting capacity assessment. Data of this study are/will be stored in the Research Electronic Data Capture (REDCap). We plan to present and publish our study findings through presentations and manuscripts. Trial

  19. 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

  20. Effect of diesel exhaust particles on renal vascular responses in rats with chronic kidney disease.

    Science.gov (United States)

    Al Suleimani, Y M; Al Mahruqi, A S; Al Za'abi, M; Shalaby, A; Ashique, M; Nemmar, A; Ali, B H

    2017-02-01

    Several recent studies have indicated the possible association between exposure to particulate air pollution and the increased rate of morbidity and mortality in patients with kidney diseases. The link of this observation to vascular damage has not been adequately addressed. Therefore, this study aims to investigate possible vascular damage that might be associated with exposure to diesel exhaust particles (DP) in adenine (AD)-induced chronic kidney disease (CKD) in rats, and the possible ameliorative effect of gum acacia (GA). CKD was induced by feeding AD (0.75%, w/w), and DP (0.5 mg/kg) was instilled intratracheally every second day and GA was given concomitantly in the drinking water at a dose of 15% w/v. All treatments were given concomitantly for 28 days. Changes in renal blood flow (RBF) and systolic and diastolic blood pressure were monitored in these animals after anesthesia, together with several other endpoints. Exposure to DP significantly reduced RBF and this was significantly potentiated in AD-treated rats. Phenylephrine-induced decreases in RBF and increases in systolic and diastolic blood pressure were severely potentiated in rats exposed to DP, and these actions were significantly augmented in AD-treated rats. GA did not significantly affect the vascular impairment induced by AD and DP given together. This study provides experimental evidence that exposure to particulate air pollution can exacerbate the vascular damage seen in patients with CKD. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 541-549, 2017.

  1. Contribution of different local vascular responses to mid-gestational vasodilation

    NARCIS (Netherlands)

    Drongelen, J. van; Pertijs, J.C.L.M.; Wouterse, A.C.; Hermsen, R.; Sweep, F.C.; Lotgering, F.K.; Smits, P.; Spaanderman, M.E.A.

    2011-01-01

    OBJECTIVE: At-term pregnancy-induced vasodilation is the resultant of endothelium-dependent vasodilation, decreased myogenic reactivity, increased compliance, and reduced sensitivity to vasoconstrictor agents. We hypothesized that these vascular changes are already present at mid-gestation. STUDY

  2. Hydroxy-oleic acid, but not oleic acid, inhibits pharmacologic vascular responsiveness in isolated aortic tissue

    Science.gov (United States)

    Oleic acid (OA) and other fatty acids can become abundant in the systemic circulation after air pollution exposure as endogenously released lipolysis byproducts or by entering the body as a component of air pollution. Vascular damage has been observed with OA infusion, but it is ...

  3. Augmentation of radiation response by motesanib, a multikinase inhibitor that targets vascular endothelial growth factor receptors.

    NARCIS (Netherlands)

    Kruser, T.J.; Wheeler, D.L.; Armstrong, E.A.; Iida, M.; Kozak, K.R.; Kogel, A.J. van der; Bussink, J.; Coxon, A.; Polverino, A.; Harari, P.M.

    2010-01-01

    BACKGROUND: Motesanib is a potent inhibitor of vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3, platelet-derived growth factor receptor, and Kit receptors. In this report we examine the interaction between motesanib and radiation in vitro and in head and neck squamous cell carcinoma

  4. Transfected Early Growth Response Gene-1 DNA Enzyme Prevents Stenosis and Occlusion of Autogenous Vein Graft In Vivo

    Directory of Open Access Journals (Sweden)

    Chengwei Liu

    2013-01-01

    Full Text Available The aim of this study was to detect the inhibitory action of the early growth response gene-1 DNA enzyme (EDRz as a carrying agent by liposomes on vascular smooth muscle cell proliferation and intimal hyperplasia. An autogenous vein graft model was established. EDRz was transfected to the graft vein. The vein graft samples were obtained on each time point after surgery. The expression of the EDRz transfected in the vein graft was detected using a fluorescent microscope. Early growth response gene-1 (Egr-1 mRNA was measured using reverse transcription-PCR and in situ hybridization. And the protein expression of Egr-1 was detected by using western blot and immunohistochemistry analyses. EDRz was located at the media of the vein graft from 2 to 24 h, 7 h after grafting. The Egr-1 protein was mainly located in the medial VSMCs, monocytes, and endothelium cells during the early phase of the vein graft. The degree of VSMC proliferation and thickness of intima were obviously relieved compared with the no-gene therapy group. EDRz can reduce Egr-1 expression in autogenous vein grafts, effectively restrain VSMC proliferation and intimal hyperplasia, and prevent vascular stenosis and occlusion after vein graft.

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

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    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.

  6. The small fibrinopeptide Bβ15-42 as renoprotective agent preserving the endothelial and vascular integrity in early ischemia reperfusion injury in the mouse kidney.

    Directory of Open Access Journals (Sweden)

    Anja Urbschat

    Full Text Available Disruption of the renal endothelial integrity is pivotal for the development of a vascular leak, tissue edema and consequently acute kidney injury. Kidney ischemia amplifies endothelial activation and up-regulation of pro-inflammatory mechanisms. After restoring a sufficient blood flow, the kidney is damaged through complex pathomechanisms that are classically referred to as ischemia and reperfusion injury, where the disruption of the inter-endothelial connections seems to be a crucial step in this pathomechanism. Focusing on the molecular cell-cell interaction, the fibrinopeptide Bβ15-42 prevents vascular leakage by stabilizing these inter-endothelial junctions. The peptide associates with vascular endothelial-cadherin, thus preventing early kidney dysfunction by preserving blood perfusion efficacy, edema formation and thus organ dysfunction. We intended to demonstrate the early therapeutic benefit of intravenously administered Bβ15-42 in a mouse model of renal ischemia and reperfusion. After 30 minutes of ischemia, the fibrinopeptide Bβ15-42 was administered intravenously before reperfusion was commenced for 1 and 3 hours. We show that Bβ15-42 alleviates early functional and morphological kidney damage as soon as 1 h and 3 h after ischemia and reperfusion. Mice treated with Bβ15-42 displayed a significantly reduced loss of VE-cadherin, indicating a conserved endothelial barrier leading to less neutrophil infiltration which in turn resulted in significantly reduced structural renal damage. The significant reduction in tissue and serum neutrophil gelatinase-associated lipocalin levels reinforced our findings. Moreover, renal perfusion analysis by color duplex sonography revealed that Bβ15-42 treatment preserved resistive indices and even improved blood velocity. Our data demonstrate the efficacy of early therapeutic intervention using the fibrinopeptide Bβ15-42 in the treatment of acute kidney injury resulting from ischemia and

  7. Ultrasound -- Vascular

    Science.gov (United States)

    ... News Physician Resources Professions Site Index A-Z Ultrasound - Vascular Vascular ultrasound uses sound waves to evaluate ... the limitations of Vascular Ultrasound? What is Vascular Ultrasound? Ultrasound is safe and painless, and produces pictures ...

  8. Ultrasound -- Vascular

    Science.gov (United States)

    ... Physician Resources Professions Site Index A-Z Ultrasound - Vascular Vascular ultrasound uses sound waves to evaluate the ... are the limitations of Vascular Ultrasound? What is Vascular Ultrasound? Ultrasound is safe and painless, and produces ...

  9. The Early Endocrine Stress Response in Experimental Subarachnoid Hemorrhage.

    Directory of Open Access Journals (Sweden)

    Christoffer Nyberg

    Full Text Available In patients with severe illness, such as aneurysmal subarachnoid hemorrhage (SAH, a physiologic stress response is triggered. This includes activation of the hypothalamic-pituitary-adrenal (HPA axis and the sympathetic nervous system. The aim of this study was to investigate the very early responses of these systems.A porcine animal model of aneurysmal SAH was used. In this model, blood is injected slowly to the basal cisterns above the anterior skull base until the cerebral perfusion pressure is 0 mm Hg. Sampling was done from blood and urine at -10, +15, +75 and +135 minutes from time of induction of SAH. Analyses of adrenocorticotropic hormone (ACTH, cortisol, aldosterone, catecholamines and chromogranin-A were performed.Plasma ACTH, serum cortisol and plasma aldosterone increased in the samples following induction of SAH, and started to decline after 75 minutes. Urine cortisol also increased after SAH. Urine catecholamines and their metabolites were found to increase after SAH. Many samples were however below detection level, not allowing for statistical analysis. Plasma chromogranin-A peaked at 15 minutes after SAH, and thereafter decreased.The endocrine stress response after aneurysmal SAH was found to start within 15 minutes in the HPA axis with early peak values of ACTH, cortisol and aldosterone. The fact that the concentrations of the HPA axis hormones decreased 135 minutes after SAH may suggest that a similar pattern exists in SAH patients, thus making it difficult to catch these early peak values. There were also indications of early activation of the sympathetic nervous system, but the small number of valid samples made interpretation difficult.

  10. Evaluation of early imaging response criteria in glioblastoma multiforme

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    Millar Barbara-Ann

    2011-09-01

    Full Text Available Abstract Background 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. Methods 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. Results 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 25% in volume or > 15% in area were most predictive of OS. Conclusions 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.

  11. Attenuated NOx responses and myocardial ischemia, a possible risk for structural vascular disease in African men: the SABPA study.

    Science.gov (United States)

    Uys, A S; Malan, L; van Rooyen, J M; Steyn, H S; Reimann, M; Ziemssen, T

    2014-07-01

    Chronically elevated blood pressure has been associated with impaired NO-mediated vasodilation and structural vascular disease risk. This study aimed to determine whether significant associations exist regarding NO metabolite (NOx) responses, cardiovascular function and structural vascular disease in a cohort of African and Caucasian men. The study included 81 African and 94 Caucasian male teachers stratified via median splits into low and high NOx ethnic groups. Ambulatory blood pressure, electrocardiogram monitoring and ultrasound carotid intima-media thickness (CIMT) images were obtained. Cardiovascular measurements and fasting blood for NOx responses were measured during rest and on challenging the cardiovascular system with the Stroop colour-word conflict test. African men displayed significantly higher resting NOx as well as higher number of 24 h silent ischemic events than their Caucasian counterparts. Low NOx African men displayed enhanced α-adrenergic and ECG ST segment depression acute mental stress responses as well as 24 h silent ischemic events associated with CIMT (adjusted R(2) = 0.47; β = 0.25; confidence interval (CI) = 0.13, 0.41). African men demonstrated a vulnerable cardiovascular profile. Novel findings revealed α-adrenergic-driven blood pressure responses and less NO bioavailability during acute stress. The association between myocardial ischemia and CIMT in this group emphasized their risk for future coronary artery disease and cerebrovascular events.

  12. 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.

  13. Gene regulation in the immediate-early response process.

    Science.gov (United States)

    Bahrami, Shahram; Drabløs, Finn

    2016-09-01

    Immediate-early genes (IEGs) can be activated and transcribed within minutes after stimulation, without the need for de novo protein synthesis, and they are stimulated in response to both cell-extrinsic and cell-intrinsic signals. Extracellular signals are transduced from the cell surface, through receptors activating a chain of proteins in the cell, in particular extracellular-signal-regulated kinases (ERKs), mitogen-activated protein kinases (MAPKs) and members of the RhoA-actin pathway. These communicate through a signaling cascade by adding phosphate groups to neighboring proteins, and this will eventually activate and translocate TFs to the nucleus and thereby induce gene expression. The gene activation also involves proximal and distal enhancers that interact with promoters to simulate gene expression. The immediate-early genes have essential biological roles, in particular in stress response, like the immune system, and in differentiation. Therefore they also have important roles in various diseases, including cancer development. In this paper we summarize some recent advances on key aspects of the activation and regulation of immediate-early genes. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Vascular function, inflammation, and variations in cardiac autonomic responses to particulate matter among welders.

    Science.gov (United States)

    Fang, Shona C; Cavallari, Jennifer M; Eisen, Ellen A; Chen, Jiu-Chiuan; Mittleman, Murray A; Christiani, David C

    2009-04-01

    Patients with health conditions associated with impaired vascular function and inflammation may be more susceptible to the adverse health effects of fine particulate (particulate matter with a mass median aerodynamic diameter of personal PM(2.5) exposure information was collected over a total of 36 person-days, including either or both welding and nonwelding days. Linear mixed models were used to examine the 5-minute standard deviation of normal-to-normal intervals (SDNN) in relation to the moving PM(2.5) averages in the preceding 1-4 hours. C-reactive protein levels and 3 measures of vascular function (augmentation index, mean arterial pressure, and pulse pressure) were determined at baseline. The authors observed an inverse association between the 1-hour PM(2.5) and 5-minute SDNN. Greater SDNN declines were observed among those with C-reactive protein (P(interaction) values at or above the 75th percentile and pulse pressure values below the 75th percentile (P < 0.001). Systemic inflammation and poorer vascular function appear to aggravate particle-related declines in heart rate variability among workers.

  15. Impaired cardiac response to exercise in post-menopausal women: relationship with peripheral vascular function.

    Science.gov (United States)

    Yoshioka, J; Node, K; Hasegawa, S; Paul, A K; Mu, X; Maruyama, K; Nakatani, D; Kitakaze, M; Hori, M; Nishimura, T

    2003-04-01

    Endothelial dysfunction has been demonstrated in post-menopausal women. To assess the relationship between peripheral vascular reserve and cardiac function during exercise in post-menopausal women, 91 subjects, who had no ischaemic findings on myocardial SPECT, were assigned to four groups: pre-menopausal women (n=13), post-menopausal women (n=33), younger men aged 50 years (n=35). First-pass radionuclide angiography was performed before and during bicycle exercise to calculate ejection fraction (EF) and peripheral vascular resistance (VR). There were no differences in haemodynamic variables among the groups at baseline. The per cent increase in EF=(exercise EF - resting EF)x100/resting EF, and the per cent decrease in VR=(resting VR - exercise VR)x100/resting VR were depressed in the post-menopausal women (0.4+/-2% and 35+/-3%, respectively) compared to the pre-menopausal women (10+/-3% and 47+/-3%, respectively; PPost-menopausal women exhibited depressed cardiac function during exercise, which may be related to the impairment of peripheral vascular function after menopause.

  16. Loss of transcription factor early growth response gene 1 results in impaired endochondral bone repair.

    Science.gov (United States)

    Reumann, Marie K; Strachna, Olga; Yagerman, Sarah; Torrecilla, Daniel; Kim, Jihye; Doty, Stephen B; Lukashova, Lyudmila; Boskey, Adele L; Mayer-Kuckuk, Philipp

    2011-10-01

    Transcription factors that play a role in ossification during development are expected to participate in postnatal fracture repair since the endochondral bone formation that occurs in embryos is recapitulated during fracture repair. However, inherent differences exist between bone development and fracture repair, including a sudden disruption of tissue integrity followed by an inflammatory response. This raises the possibility that repair-specific transcription factors participate in bone healing. Here, we assessed the consequence of loss of early growth response gene 1 (EGR-1) on endochondral bone healing because this transcription factor has been shown to modulate repair in vascularized tissues. Model fractures were created in ribs of wild type (wt) and EGR-1(-/-) mice. Differences in tissue morphology and composition between these two animal groups were followed over 28 post fracture days (PFDs). In wt mice, bone healing occurred in healing phases characteristic of endochondral bone repair. A similar healing sequence was observed in EGR-1(-/-) mice but was impaired by alterations. A persistent accumulation of fibrin between the disconnected bones was observed on PFD7 and remained pronounced in the callus on PFD14. Additionally, the PFD14 callus was abnormally enlarged and showed increased deposition of mineralized tissue. Cartilage ossification in the callus was associated with hyper-vascularity and -proliferation. Moreover, cell deposits located in proximity to the callus within skeletal muscle were detected on PFD14. Despite these impairments, repair in EGR-1(-/-) callus advanced on PFD28, suggesting EGR-1 is not essential for healing. Together, this study provides genetic evidence that EGR-1 is a pleiotropic regulator of endochondral fracture repair. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. Vascular hyperpermeability in response to inflammatory mustard oil is mediated by Rho kinase in mice systemically exposed to arsenic.

    Science.gov (United States)

    Chen, Shih-Chieh; Liu, Chun-Chih; Huang, Shin-Yin; Chiou, Shean-Jaw

    2011-09-01

    The mechanisms underlying vascular dysfunction and cardiovascular disease induced by chronic arsenic exposure are not completely understood. We have previously shown that mice chronically fed sodium arsenite are hypersensitive to the permeability-increasing effects of inflammatory mustard oil. The aim of this study was to investigate whether RhoA/Rho kinase (ROCK)-mediated vascular leakage (hyperpermeability) is induced by mustard oil in mice systemically exposed to arsenic. Animals were orally fed water (control group) or sodium arsenite for 8weeks. We compared the blood pressure and microvessel density of the ears between these two groups. Both control and arsenic groups exhibited a similar mean arterial pressure and microvessel density. Microvessel permeability changes that occurred following mustard oil treatment in the presence of Y-27632, a ROCK inhibitor, were quantified using the Evans blue (EB) technique and vascular labeling with carbon particles. Both the excessive leakiness of EB and the high density of carbon-labeled microvessels upon stimulation with mustard oil in the arsenic-fed mice were reduced by Y-27632 treatment. However, RhoA and ROCK2 expression levels were similar between control and arsenic-fed mice. We further investigated ROCK2 levels and ROCK activity in the ears following mustard oil challenge. ROCK2 levels in mouse ears treated with mustard oil were higher in the arsenic group as compared with the control group. Following mustard oil application, ROCK activity was significantly higher in the arsenic-fed mice compared with the control mice. These findings indicate that increased ROCK2 levels and enhanced ROCK activity are responsible for mustard oil-induced vascular hyperpermeability in arsenic-fed mice. Copyright © 2011 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Jan Skóra

    2012-07-01

    Full Text Available  Introduction: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.Material/Methods: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.Results: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.Discussion: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.

  19. 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 sexo, idade e índice de massa corporal (IMC) sobre a EMIC em cada grupo. Estudo observacional de coorte. Um total de 133 indivíduos hipertensos (sexo masculino, n = 69; idade média 10.5 ± 4 anos) foi submetido à ultrassonografia das artérias carótidas para avaliação da EMIC. Cento e vinte e um indivíduos saudáveis (sexo masculino, n = 64; idade média, 9.8 ± 4.1 anos) foram selecionados como controles para as seguintes características: sexo, idade (± 1ano) e IMC (±10%). Não houve diferenças significativas entre os grupos com relação ao sexo (p = 0,954) e idade (p = 0,067). Os indivíduos hipertensos apresentaram maior IMC (p = 0,004), porém dentro da faixa estabelecida de até 10%. Os indivíduos hipertensos apresentaram maiores valores de EMIC quando comparados ao grupo-controle (0,46 ± 0,05 versus 0,42 ± 0,05 mm

  20. Analysis of the vascular responses in a murine model of polycystic ovary syndrome.

    Science.gov (United States)

    Labruijere, Sieneke; van Houten, E Leonie A F; de Vries, René; Musterd-Bagghoe, Usha M; Garrelds, Ingrid M; Kramer, Piet; Danser, A H Jan; Villalón, Carlos M; Visser, Jenny A; Van Den Brink, Antoinette Maassen

    2013-01-01

    Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of there productive age, but the exact pathophysiological mechanisms involved remain unclear. Cardiovascular disease risk is increased in PCOS patients and endothelial damage has been observed. We recently developed a mouse model of PCOS with reproductive and metabolic characteristics resembling those observed in women with PCOS. In this model we studied vascular function with particular emphasis on markers of vascular endothelial function. Animals were treated for 90 days with dihydrotestosterone (DHT; 27.5 mg/day) or placebo using subcutaneous continuous-release pellets. Aortas were isolated for isometric force recordings in organ baths to investigate endothelial and vascular smooth muscle characteristics. Lungs were used to analyze endothelial nitric oxide synthase (eNOS) expression and phosphorylation. Asymmetric dimethylarginine (ADMA) levels were investigated in serum to assess endothelial damage. Expression of androgen receptor (Ar) mRNA was studied in aortas. DHT treatment (compared with placebo) induced i) a significant decrease in acetylcholine-induced aortic relaxations, with no change in calcitonin gene related peptide- or sodium nitroprusside-induced relaxations, as well as 5-hydroxytryptamine-induced contractions; ii) no change in eNOS expression/phosphorylation in lungs or in plasma ADMA levels; and iii) a twofold increase in aortic AR expression. Our results suggest that, in DHT-exposed mice, hyperandrogenemia specifically decreases endothelium dependent vasorelaxation without deterioration of smooth muscle function. This study may initiate further investigations to elucidate underlying mechanism for the phenotype that is present in these animals, as well as in PCOS patients.

  1. Atheroprotective remodelling of vascular dermatan sulphate proteoglycans in response to hypercholesterolaemia in a rat model.

    Science.gov (United States)

    Oberkersch, Roxana; Maccari, Francesca; Bravo, Alicia I; Volpi, Nicola; Gazzaniga, Silvina; Calabrese, Graciela C

    2014-06-01

    Proteoglycan accumulation within the arterial intima has been implicated in atherosclerosis progression in humans. Nevertheless, hypercholesterolaemia is unable to induce intimal thickening and atheroma plaque development in rats. The study was performed to analyse proteoglycans modifications in rats fed with a high-cholesterol diet to understand whether vascular wall remodelling protects against lesions. Sections obtained from rat aortas showed normal features, in intimal-to-media ratio and lipid accumulation. However, focal endothelial hyperplasia and neo-intima rearrangement were observed in high-cholesterol animals. Besides, hypercholesterolaemia induced an inflammatory microenviroment. We determined the expression of different proteoglycans from aortic cells by Western blot and observed a diminished production of decorin and biglycan in high-cholesterol animals compared with control (P < 0.01 and P < 0.05, respectively). Versican was increased in high-cholesterol animals (P < 0.05), whereas perlecan production showed no differences. No modification of the total content of glycosaminoglycans (GAGs) was found between the two experimental groups. In contrast, the chondroitin sulphate/dermatan sulphate ratio was increased in the high-cholesterol group as compared to the control (0.56 and 0.34, respectively). Structural alterations in the disaccharide composition of galactosaminoglycans were also detected by HPLC, as the ratio of 6-sulphate to 4-sulphate disaccharides was increased in high-cholesterol animals (P < 0.05). Our results suggest that attenuation of decorin and biglycan expression might be an effective strategy to inhibit the first step in atherogenesis, although specific GAG structural modification associated with the development of vascular disease took place. Results emphasize the potential application of therapies based on vascular matrix remodelling to treat atherosclerosis. © 2014 The Authors. International Journal of Experimental

  2. 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.

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

    Science.gov (United States)

    Gatheral, Timothy; Reed, Daniel M; Moreno, Laura; Gough, Peter J; Votta, Bart J; Sehon, Clark A; Rickard, David J; Bertin, John; Lim, Eric; Nicholson, Andrew G; Mitchell, Jane A

    2012-01-01

    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.

  4. Preoperative nutritional status predicts the severity of the systemic inflammatory response syndrome (SIRS) following major vascular surgery.

    Science.gov (United States)

    Hassen, T A; Pearson, S; Cowled, P A; Fitridge, R A

    2007-06-01

    This study examined the relationship between pre-operative nutritional status and systemic inflammatory response syndrome (SIRS) or sepsis following major vascular surgery. Subjects undergoing open AAA repair, EVAR or lower limb revascularisation were studied prospectively. Pre-operative nutrition was assessed clinically using Mini-Nutritional Assessment (MNA) and body composition was measured by dual energy X-ray absorptiometry (DEXA) scanning. SIRS severity was assessed for 5 post-operative days and sepsis noted within 30 days of surgery. Using MNA, neither SIRS severity nor sepsis occurrence differed significantly between 'well-nourished' subjects and those 'at risk of malnutrition'. Using DEXA, negative associations existed between body mass index and both SIRS score and SIRS duration. Fat free mass (FFM) was negatively associated with SIRS score and duration. Negative associations also existed between skeletal muscle mass (SMM) and SIRS score and duration. SMM was also negatively correlated with post-operative length of stay in hospital. There were no significant correlations between sepsis and any nutritional indices. Lower pre-operative nutritional indices, indicating protein energy malnutrition, were associated with more severe systemic inflammatory responses following major vascular surgery.

  5. 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.

  6. Selective impact of early parental responsivity on adolescent stress reactivity.

    Directory of Open Access Journals (Sweden)

    Daniel A Hackman

    Full Text Available Research in animals has shown that early life experience, particularly parenting behaviors, influences later-life stress reactivity. Despite the tremendous relevance of this finding to human development and brain function, it has not been tested prospectively in humans. In this study two aspects of parenting were measured at age 4 in a sample of healthy, low socioeconomic status, African American children, and stress reactivity was measured in the same children 11-14 years later using a modified version of the Trier Social Stress Test (n = 55. Salivary cortisol was measured before, during and after the stressor and data were analyzed using piecewise hierarchical linear modeling. Parental responsivity, independent of the use of physical discipline, was positively related to cortisol reactivity. Effects were independent of subjective appraisals of the stressor and were also independent of other environmental risk factors and current psychosocial functioning. Therefore this study demonstrates in a novel and precise fashion that early childhood parental responsivity prospectively and independently predicts stress reactivity in adolescence.

  7. Early vascular unclamping reduces warm ischaemia time in robot-assisted laparoscopic partial nephrectomy [v1; ref status: indexed, http://f1000r.es/570

    Directory of Open Access Journals (Sweden)

    Kevin Lah

    2015-05-01

    Full Text Available Introduction: The aim of this study was to assess the outcomes of early vascular release in robot-assisted laparoscopic partial nephrectomy (RAPN to reduce warm ischaemia time (WIT and minimise renal dysfunction. RAPN is increasingly utilised in the management of small renal masses. To this end it is imperative that WIT is kept to a minimum to maintain renal function. Methods: RAPN was performed via a four-arm robotic transperitoneal approach. The renal artery and vein were individually clamped with robotic vascular bulldog clamps to allow cold scissor excision of the tumour. The cut surface was then sutured with one or two running 3-0 V-LocTM sutures, following which the vascular clamps were released. Specific bleeding vessels were then selectively oversewn and the collecting system repaired. Renorrhaphy was then completed using a running horizontal mattress 0-0 V-LocTM suture. Results: A total of 16 patients underwent RAPN with a median WIT of 15 minutes (range: 8-25, operative time 230 minutes (range: 180-280 and blood loss of 100 mL (range: 50-1000. There were no transfusions, secondary haemorrhages or urine leaks. There was one focal positive margin in a central 5.5 cm pT3a renal cell carcinomas (RCC. Long-term estimated glomerular filtration rate (eGFR was not significantly different to pre-operative values. Conclusion: In this patient series, early vascular release effectively minimised WIT and maintained renal function without compromising perioperative safety.

  8. Pulmonary vascular response during phases of canine heartworm disease: scanning electron microscopic study.

    Science.gov (United States)

    Schaub, R G; Rawlings, C A

    1980-07-01

    Pulmonary arteries and veins of 14 dogs in phases of heartworm disease (Dirofilaria immitis infection) were examined by scanning electron microscopy. Two dogs were infected with D immitis microfilaria only, whereas 12 dogs were infected with adult D immitis. Seven of the dogs infected with adult worms were untreated. Two of these 7 dogs had natural infections of unknown duration introduced by mosquito bite, whereas 5 were experimentally infected for 30 days. The remaining five dogs were experimentally infected for 1 year and had worms removed by drug therapy. These five dogs were maintained 12 months after treatment. Arteries and veins from dogs infected with microfilaria had a continuous sheet of endothelial cells. Arterial endothelium from the seven nontreated dogs infected with adult heartworms exhibited swirling patterns, pore formation, and separation of intercellular junctions. Arteries from all dogs had numerous endothelialized villus protrusions; veins had similar, less extensive changes. Arteries and veins from experimentally infected dogs were similar to naturally infected dogs, indicating the infection procedure produced lesions similar to that normally seen in heartworm disease. The extent of vascular lesions was reduced in four of the five treated dogs that had been infected with adult worms. Adult worms, not microfilaria, may produce the vascular lesions seen in heartworm disease. Lesions will regress if worms are removed from the circulation. Lesions may be caused by generation of humoral factors initiated by the presence of adult worms.

  9. Early prediction of blonanserin response in Japanese patients with schizophrenia.

    Science.gov (United States)

    Kishi, Taro; Matsuda, Yuki; Fujita, Kiyoshi; Iwata, Nakao

    2014-01-01

    Blonanserin is a second-generation antipsychotic used for the treatment of schizophrenia in Japan and Korea. The present study aimed to examine early prediction of blonanserin in patients with schizophrenia. An 8-week, prospective, single-arm, flexible-dose clinical trial of blonanserin in patients with schizophrenia was conducted under real-world conditions. The inclusion criteria were antipsychotic naïve, and first-episode schizophrenia patients or schizophrenia patients with no consumption of any antipsychotic medication for more than 4 weeks before enrollment in this study. The positive predictive value, negative predictive value, sensitivity, specificity, and predictive power were calculated for the response status at week 4 to predict the subsequent response at week 8. Thirty-seven patients were recruited (56.8% of them had first-episode schizophrenia), and 28 (75.7%) completed the trial. At week 8, blonanserin was associated with a significant improvement in the Positive and Negative Syndrome Scale (PANSS) total score (Pblonanserin response at week 4 could predict the later response at week 8.

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

    OpenAIRE

    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 t...

  11. 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.)

  12. Early Exercise Promotes Angiogenic Response in Mice Model of Myocardial Infarction

    Institute of Scientific and Technical Information of China (English)

    Wu Guifu; Du Zhimin; Hu Chenghen; Roger J. Laham

    2005-01-01

    Objectives Little is known about the mechanism of exercise-induced angiogenic response in ischemic myocardium. This study was designed to investigate the effects of exercise training on expression of vascular endothelial growth factor and angiogenesis in infarcted heart. Methods Fifty male FVB mice were divided into three subgroups to test various responses to exercise, including timedependent response of angiogenic factors to exercise training in intact heart (n=10) and infarcted heart (n=10), as well as exercise-induced angiogenic response in heart with myocardial infarction (MI) (n=30). The mice in the exercise-training groups were allowed to exercise daily at 1 hour per day for 7 days. Results VEGF protein expression was up-regulated by exercise training in time dependent fashion in mice with MI.Angiogenesis was evident by increased myocardial microvessels observed by PECAM-1 immunohistoc-hemical staining in post-MI exercise group (16.5±3.4)/0.4 mm2 versus post-MI sedentary mice ( 10±2.1 )/0.4 mm2 (P < 0.05). Cell proliferation assessment showed significantly higher (P < 0.05) number of BrdU positive cells in post MI mice in exercise group as opposed to sedentary post MI mice. 2%TTC staining disclosed a profound difference in the size of MI (18.25±2.93)% in exercise group vs sedentary group (29.26±7.64)% (P<0.05). Conclusions Activation and up-regulation of VEGF in infarcted mice heart may contributes the angiogenic response to exercise training at the early stage of myocardial infarction. This underscores the impact of exercise on angiogenesis in post myocardial infarction setting.

  13. 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

  14. Early prediction of blonanserin response in Japanese patients with schizophrenia

    Directory of Open Access Journals (Sweden)

    Kishi T

    2014-09-01

    Full Text Available Taro Kishi,1 Yuki Matsuda,1 Kiyoshi Fujita,2,3 Nakao Iwata1 1Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan; 2Department of Psychiatry, Okehazama Hospital, Toyoake, Aichi, Japan; 3The Neuroscience Research Center, Toyoake, Aichi, Japan Background: Blonanserin is a second-generation antipsychotic used for the treatment of schizophrenia in Japan and Korea. The present study aimed to examine early prediction of blonanserin in patients with schizophrenia. Methods: An 8-week, prospective, single-arm, flexible-dose clinical trial of blonanserin in patients with schizophrenia was conducted under real-world conditions. The inclusion criteria were antipsychotic naïve, and first-episode schizophrenia patients or schizophrenia patients with no consumption of any antipsychotic medication for more than 4 weeks before enrollment in this study. The positive predictive value, negative predictive value, sensitivity, specificity, and predictive power were calculated for the response status at week 4 to predict the subsequent response at week 8.Results: Thirty-seven patients were recruited (56.8% of them had first-episode schizophrenia, and 28 (75.7% completed the trial. At week 8, blonanserin was associated with a significant improvement in the Positive and Negative Syndrome Scale (PANSS total score (P<0.0001 and in positive (P<0.0001, negative (P<0.0001, and general subscale scores (P<0.0001. In terms of percentage improvement of PANSS total scores from baseline to week 8, 64.9% of patients showed a ≥20% reduction in the PANSS total score and 48.6% showed a ≥30% reduction. However, 8.1% of patients experienced at least one adverse event. Using the 20% reduction in the PANSS total score at week 4 as a definition of an early response, the negative predictive values for later responses (ie, reductions of ≥30 and ≥40 in the PANSS total scores were 88.9% and 94.1%, respectively. The specificities were 80.0% and

  15. CKII-SIRT1-SM22α loop evokes a self-limited inflammatory response in vascular smooth muscle cells.

    Science.gov (United States)

    Shu, Ya-Nan; Dong, Li-Hua; Li, Han; Pei, Qian-Qian; Miao, Sui-Bing; Zhang, Fan; Zhang, Dan-Dan; Chen, Rong; Yin, Ya-Juan; Lin, Yan-Ling; Xue, Zhen-Ying; Lv, Pin; Xie, Xiao-Li; Zhao, Li-Li; Nie, Xi; Chen, Peng; Han, Mei

    2017-08-01

    Sirtuin 1 (SIRT1) inhibits nuclear factor kappa B (NF-κB) activity in response to the inflammatory cytokine tumour necrosis factor alpha (TNF-α). Smooth muscle (SM) 22α is a phosphorylation-regulated suppressor of IKK-IκBα-NF-κB signalling cascades in vascular smooth muscle cells (VSMCs). Sm22α knockout results in increased expression of pro-inflammatory genes in the aortas which are controlled by NF-κB. This study aimed to investigate the relationship between SM22α and SIRT1 in the control of vascular inflammation. The ligation injury model of Sirt1-Tg/Sm22α-/- mice displayed an increased level of the inflammatory molecules in the carotid arteries compared with Sirt1-Tg mice, accompanied with aggravating neointimal hyperplasia. In the in vitro study, on the one hand, we showed that TNF-α induced the epigenetic silencing of SM22α transcription via EZH2-mediated H3K27 methylation in the SM22α promoter region, contributing to inflammatory response. On the other hand, TNF-α simultaneously induced SIRT1 phosphorylation via CKII and thereby protected against inflammation. Phosphorylated SIRT1 interacted with and deacetylated EZH2 and, subsequently, promoted SM22α transcription by inhibiting EZH2 activity. Increased SM22α in turn facilitated the phosphorylation and activation of SIRT1 via recruitment of CKII to SIRT1, which amplified the anti-inflammatory effect of SIRT1. Our findings demonstrate that, in response to TNF-α stimulation, CKII-SIRT1-SM22α acts in a loop to reinforce the expression of SM22α, which limits the inflammatory response in VSMCs in vivo and in vitro. The anti-inflammatory effect of SIRT1 may be dependent on SM22α to some extent. Our data point to targeted activation of SIRT1 in VSMCs as a promising therapeutic avenue in preventing cardiovascular diseases.

  16. 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.

  17. Brief Report: Power Doppler Ultrasonography for Detection of Increased Vascularity in the Fascia: A Potential Early Diagnostic Tool in Fasciitis of Dermatomyositis.

    Science.gov (United States)

    Yoshida, Ken; Nishioka, Makiko; Matsushima, Satoshi; Joh, Kensuke; Oto, Yosuke; Yoshiga, Masayuki; Otani, Kazuhiro; Ito, Haruyasu; Hirai, Kenichiro; Furuya, Kazuhiro; Ukichi, Taro; Noda, Kentaro; Kingetsu, Isamu; Kurosaka, Daitaro

    2016-12-01

    We previously demonstrated that fasciitis is a common lesion of dermatomyositis (DM) that is detectable early after disease onset by en bloc muscle biopsy combined with magnetic resonance imaging (MRI). Power Doppler ultrasonography (PDUS) is a useful method for detection of inflammation and vascularity in rheumatic diseases. We undertook this study to determine whether fasciitis was detectable by PDUS in patients with DM. We prospectively evaluated 7 patients with DM and 7 patients with polymyositis (PM) for the detection of fasciitis with PDUS. MRI and PDUS were both performed in all patients. Fasciitis was histologically confirmed by en bloc biopsy. Among all patients with DM, 4 showed signs of fasciitis on MRI, while increased blood flow signals were observed along the fascia by PDUS in 6 DM patients, including 4 patients with early disease (fascia. Immunohistochemical staining for CD31 indicated abnormal neovascular proliferation in the fascia in patients with DM. None of the PM patients showed signs of fasciitis or increased vascularity by MRI, PDUS, or en bloc biopsy. In our limited population, PDUS was useful for the detection of fasciitis associated with DM, especially in the early stage of disease. The increased blood flow signal as detected by PDUS is involved in angiogenesis accompanying fasciitis in patients with DM. © 2016, American College of Rheumatology.

  18. Statin use is associated with early recovery of kidney injury after vascular surgery and improved long-term outcome

    NARCIS (Netherlands)

    G.M.J.M. Welten (Gijs); M. Chonchol (Michel); O. Schouten (Olaf); S.E. Hoeks (Sanne); J.J. Bax (Jeroen); R.T. van Domburg (Ron); M.R.H.M. van Sambeek (Marc); D. Poldermans (Don)

    2008-01-01

    textabstractBackground. Acute kidney injury (AKI) after major vascular surgery is an important risk factor for adverse long-term outcomes. The pleiotropic effects of statins may reduce kidney injury caused by perioperative episodes of hypotension and/or suprarenal clamping and improve long-term

  19. Vascular Cures

    Science.gov (United States)

    ... is Possible EVERY DOLLAR SAVES LIVES. Donate Now Vascular Cures innovates patient-centered research, catalyzes breakthrough collaborations and empowers people in their vascular health journey. what is vascular disease PATIENTS see ...

  20. Vascular ring

    Science.gov (United States)

    ... subclavian and left ligamentum ateriosus; Congenital heart defect - vascular ring; Birth defect heart - vascular ring ... Vascular ring is rare. It accounts for less than 1% of all congenital heart problems. The condition ...

  1. 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.

  2. Reduced telomere length is not associated with early signs of vascular aging in young men born after intrauterine growth restriction: a paradox?

    DEFF Research Database (Denmark)

    Laganovic, M.; Bendix, L.; Rubelj, I.;

    2014-01-01

    Objective: The mechanisms that increase cardiovascular risk in individuals born small for gestational age (SGA) are not well understood. Telomere shortening has been suggested to be a predictor of disease onset. Our aim was to determine whether impaired intrauterine growth is associated with early...... signs of vascular aging and whether telomere length could be a biomarker of this pathway. Methods: One hundred and fourteen healthy young men born SGA or after normal pregnancy [appropriate for gestational age (AGA)] were enrolled. Patient data were gathered from questionnaires and clinical exams...

  3. Human Macrophage Response to L. (Viannia) panamensis: Microarray Evidence for an Early Inflammatory Response

    Science.gov (United States)

    Rojas, Ricardo; Ettinger, Nicholas A.; Tikhonova, Irina; Alexander, Neal D.; Valderrama, Liliana; Hager, Janet; Wilson, Mary E.; Lin, Aiping; Zhao, Hongyu; Saravia, Nancy G.; McMahon-Pratt, Diane

    2012-01-01

    Background Previous findings indicate that susceptibility to Leishmania (Viannia) panamensis infection of monocyte-derived macrophages from patients and asymptomatically infected individuals were associated with the adaptive immune response and clinical outcome. Methodology/Principal Findings To understand the basis for this difference we examined differential gene expression of human monocyte-derived macrophages following exposure to L. (V.) panamensis. Gene activation profiles were determined using macrophages from healthy volunteers cultured with or without stationary phase promastigotes of L. (V.) panamensis. Significant changes in expression (>1.5-fold change; p<0.05; up- or down-regulated) were identified at 0.5, 4 and 24 hours. mRNA abundance profiles varied over time, with the highest level of activation occurring at earlier time points (0.5 and 4 hrs). In contrast to observations for other Leishmania species, most significantly changed mRNAs were up- rather than down-regulated, especially at early time points. Up-regulated transcripts over the first 24 hours belonged to pathways involving eicosanoid metabolism, oxidative stress, activation of PKC through G protein coupled receptors, or mechanism of gene regulation by peroxisome proliferators via PPARα. Additionally, a marked activation of Toll-receptor mediated pathways was observed. Comparison with published microarray data from macrophages infected with L. (Leishmania) chagasi indicate differences in the regulation of genes involved in signaling, motility and the immune response. Conclusions Results show that the early (0.5 to 24 hours) human monocyte-derived macrophage response to L. (Viannia) panamensis is not quiescent, in contrast to published reports examining later response times (48–96 hours). Early macrophage responses are important for the developing cellular response at the site of infection. The kinetics and the mRNA abundance profiles induced by L. (Viannia) panamensis illustrate the

  4. Vascular and hormonal responses to arginine: provision of substrate for nitric oxide or non-specific effect?

    Science.gov (United States)

    MacAllister, R J; Calver, A L; Collier, J; Edwards, C M; Herreros, B; Nussey, S S; Vallance, P

    1995-08-01

    1. The vascular and hormonal effects of L- and D-arginine were compared in healthy subjects and in patients with insulin-dependent diabetes mellitus or untreated essential hypertension. 2. Infusion of L- or D-arginine (40 mumol/l) in the forearm vascular bed, sufficient to increase the local concentration approximately 20-fold, had no effect on blood flow or the vasodilator response to acetylcholine (30 and 100 nmol/min) in patients with insulin-dependent diabetes (n = 7) or essential hypertension (n = 7), or in age- and sex-matched control subjects (n = 7 in both groups). 3. Systemic infusion of 10 g of L-arginine (n = 5) or D-arginine (n = 3) increased plasma concentration of arginine approximately 20-fold without altering supine or erect haemodynamics. Increases in plasma insulin, prolactin and glucagon were seen with both enantiomers. The stereopurity of arginine was confirmed in a cell-culture assay system. 4. We conclude that, in healthy subjects and patients with essential hypertension or insulin-dependent diabetes, synthesis of nitric oxide within the vasculature is not limited by substrate availability. At high concentrations of arginine, non-stereospecific effects, including alterations in hormone concentration, occur. It remains to be determined whether these non-stereospecific hormonal changes might contribute to certain haemodynamic effects of arginine.

  5. Regional early and progressive loss of brain pericytes but not vascular smooth muscle cells in adult mice with disrupted platelet-derived growth factor receptor-β signaling

    Science.gov (United States)

    Nikolakopoulou, Angeliki Maria; Zhao, Zhen; Montagne, Axel

    2017-01-01

    Pericytes regulate key neurovascular functions of the brain. Studies in pericyte-deficient transgenic mice with aberrant signaling between endothelial-derived platelet-derived growth factor BB (PDGF-BB) and platelet-derived growth factor receptor β (PDGFRβ) in pericytes have contributed to better understanding of the role of pericytes in the brain. Here, we studied PdgfrβF7/F7 mice, which carry seven point mutations that disrupt PDGFRβ signaling causing loss of pericytes and vascular smooth muscle cells (VSMCs) in the developing brain. We asked whether these mice have a stable or progressive vascular phenotype after birth, and whether both pericyte and VSMCs populations are affected in the adult brain. We found an early and progressive region-dependent loss of brain pericytes, microvascular reductions and blood-brain barrier (BBB) breakdown, which were more pronounced in the cortex, hippocampus and striatum than in the thalamus, whereas VSMCs population remained unaffected at the time when pericyte loss was already established. For example, compared to age-matched controls, PdgfrβF7/F7 mice between 4–6 and 36–48 weeks of age developed a region-dependent loss in pericyte coverage (22–46, 24–44 and 4–31%) and cell numbers (36–49, 34–64 and 11–36%), reduction in capillary length (20–39, 13–46 and 1–30%), and an increase in extravascular fibrinogen-derived deposits (3.4–5.2, 2.8–4.1 and 0–3.6-fold) demonstrating BBB breakdown in the cortex, hippocampus and thalamus, respectively. Capillary reductions and BBB breakdown correlated with loss of pericyte coverage. Our data suggest that PdgfrβF7/F7 mice develop an aggressive and rapid vascular phenotype without appreciable early involvement of VSMCs, therefore providing a valuable model to study regional effects of pericyte loss on brain vascular and neuronal functions. This model could be a useful tool for future studies directed at understanding the role of pericytes in the pathogenesis

  6. Vascular plant one-zinc-finger protein 1/2 transcription factors regulate abiotic and biotic stress responses in Arabidopsis.

    Science.gov (United States)

    Nakai, Yusuke; Nakahira, Yoichi; Sumida, Hiroki; Takebayashi, Kosuke; Nagasawa, Yumiko; Yamasaki, Kanako; Akiyama, Masako; Ohme-Takagi, Masaru; Fujiwara, Sumire; Shiina, Takashi; Mitsuda, Nobutaka; Fukusaki, Eiichiro; Kubo, Yasuyuki; Sato, Masa H

    2013-03-01

    Plants adapt to abiotic and biotic stresses by activating abscisic acid-mediated (ABA) abiotic stress-responsive and salicylic acid-(SA) or jasmonic acid-mediated (JA) biotic stress-responsive pathways, respectively. Although the abiotic stress-responsive pathway interacts antagonistically with the biotic stress-responsive pathways, the mechanisms that regulate these pathways remain largely unknown. In this study, we provide insight into the function of vascular plant one-zinc-finger proteins (VOZs) that modulate various stress responses in Arabidopsis. The expression of many stress-responsive genes was changed in the voz1voz2 double mutant under normal growth conditions. Consistent with altered stress-responsive gene expression, freezing- and drought-stress tolerances were increased in the voz1voz2 double mutant. In contrast, resistance to a fungal pathogen, Colletotrichum higginsianum, and to a bacterial pathogen, Pseudomonas syringae, was severely impaired. Thus, impairing VOZ function simultaneously conferred increased abiotic tolerance and biotic stress susceptibility. In a chilling stress condition, both the VOZ1 and VOZ2 mRNA expression levels and the VOZ2 protein level gradually decreased. VOZ2 degradation during cold exposure was completely inhibited by the addition of the 26S proteasome inhibitor, MG132, a finding that suggested that VOZ2 degradation is dependent on the ubiquitin/26S proteasome system. In voz1voz2, ABA-inducible transcription factor CBF4 expression was enhanced significantly even under normal growth conditions, despite an unchanged endogenous ABA content. A finding that suggested that VOZs negatively affect CBF4 expression in an ABA-independent manner. These results suggest that VOZs function as both negative and positive regulators of the abiotic and biotic stress-responsive pathways, and control Arabidopsis adaptation to various stress conditions. © 2012 The Authors The Plant Journal © 2012 Blackwell Publishing Ltd.

  7. Effects of early exercise engagement on vascular risk in patients with transient ischemic attack and nondisabling stroke.

    Science.gov (United States)

    Faulkner, James; Lambrick, Danielle; Woolley, Brandon; Stoner, Lee; Wong, Lai-kin; McGonigal, Gerard

    2013-11-01

    The objective of this study was to conduct a randomized, parallel-group clinical trial assessed the efficacy of a health-enhancing physical activity program (exercise and education) on vascular risk factors and aerobic fitness in patients who have experienced a transient ischemic attack (TIA) or nondisabling stroke. Sixty patients (69±11 years) completed a baseline (BL) vascular risk stratification and aerobic fitness examination (cycle test) within 2 weeks of symptom onset. Subjects were then randomized to either an 8-week, twice weekly exercise program or to a usual-care control (CON) group. Postintervention (PI) assessments were completed immediately after the intervention and at 3-month follow-up. A series of primary (systolic blood pressure [SBP]) and secondary (vascular risk factors like total cholesterol [TC], high-density lipoproteins, etc.; Framingham risk score; peak oxygen uptake) outcome measures were assessed. Significantly greater reductions in SBP (mean change±SD; -10.4±9.2 mm Hg) and TC (-.53±.90 mmol/L) were observed between BL and PI assessments for the exercise group compared with the CON group (-1.9±15.4 mm Hg and -.08±.59 mmol/L, respectively) (P.05). Significant improvements in aerobic fitness were also observed and maintained at the 3-month follow-up assessment after regular exercise participation (Pexercise resulted in significant improvements in vascular risk factors and fitness in those diagnosed with TIA. As these beneficial effects were maintained up to 3 months after completing the exercise program, exercise should be considered a useful additive treatment strategy for newly diagnosed TIA patients. Future research should examine the long-term efficacy of such programs. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  8. Early role of vascular dysregulation on late-onset Alzheimer's disease based on multifactorial data-driven analysis

    OpenAIRE

    Iturria-Medina, Y.; R.C. Sotero; Toussaint, P. J.; Mateos-Pérez, J. M.; Evans, A C; Weiner, Michael W.; Aisen, Paul; Petersen, Ronald; Jack, Clifford R; Jagust, William; Trojanowki, John Q.; Toga, Arthur W; Beckett, Laurel; Green, Robert C.; Saykin, Andrew J.

    2016-01-01

    Multifactorial mechanisms underlying late-onset Alzheimer's disease (LOAD) are poorly characterized from an integrative perspective. Here spatiotemporal alterations in brain amyloid-β deposition, metabolism, vascular, functional activity at rest, structural properties, cognitive integrity and peripheral proteins levels are characterized in relation to LOAD progression. We analyse over 7,700 brain images and tens of plasma and cerebrospinal fluid biomarkers from the Alzheimer's Disease Neuroim...

  9. The rationale and design of the antihypertensives and vascular, endothelial, and cognitive function (AVEC trial in elderly hypertensives with early cognitive impairment: Role of the renin angiotensin system inhibition

    Directory of Open Access Journals (Sweden)

    Hart Meaghan

    2009-11-01

    Full Text Available Abstract Background Prior evidence suggests that the renin angiotensin system and antihypertensives that inhibit this system play a role in cognitive, central vascular, and endothelial function. Our objective is to conduct a double-blind randomized controlled clinical trial, the antihypertensives and vascular, endothelial, and cognitive function (AVEC, to compare 1 year treatment of 3 antihypertensives (lisinopril, candesartan, or hydrochlorothiazide in their effect on memory and executive function, cerebral blood flow, and central endothelial function of seniors with hypertension and early objective evidence of executive or memory impairments. Methods/Design The overall experimental design of the AVEC trial is a 3-arm double blind randomized controlled clinical trial. A total of 100 community eligible individuals (60 years or older with hypertension and early cognitive impairment are being recruited from the greater Boston area and randomized to lisinopril, candesartan, or hydrochlorothiazide ("active control" for 12 months. The goal of the intervention is to achieve blood pressure control defined as SBP 20 and without clinical diagnosis of dementia or Alzheimer's disease. Individuals who are currently receiving antihypertensives are eligible to participate if the participants and the primary care providers are willing to taper their antihypertensives. Participants undergo cognitive assessment, measurements of cerebral blood flow using Transcranial Doppler, and central endothelial function by measuring changes in cerebral blood flow in response to changes in end tidal carbon dioxide at baseline (off antihypertensives, 6, and 12 months. Our outcomes are change in cognitive function score (executive and memory, cerebral blood flow, and carbon dioxide cerebral vasoreactivity. Discussion The AVEC trial is the first study to explore impact of antihypertensives in those who are showing early evidence of cognitive difficulties that did not reach the

  10. Single Pulse Electrical Stimulation to identify epileptogenic cortex: Clinical information obtained from early evoked responses

    NARCIS (Netherlands)

    Mouthaan, B.E.; van 't Klooster, M.A.; Keizer, D.; Hebbink, Gerrit Jan; Leijten, F.S.; Ferrier, C.H.; van Putten, Michel Johannes Antonius Maria; Zijlmans, M.; Huiskamp, G.J.

    2016-01-01

    Objective Single Pulse Electrical Stimulation (SPES) probes epileptogenic cortex during electrocorticography. Two SPES responses are described: pathological delayed responses (DR, >100 ms) associated with the seizure onset zone (SOZ) and physiological early responses (ER, <100 ms) that map cortical

  11. Single pulse electrical stimulation to identify epileptogenic cortex: Clinical information obtained from early evoked responses

    NARCIS (Netherlands)

    Mouthaan, B.E.; van 't Klooster, M.A.; Keizer, D.; Hebbink, Gerrit Jan; Leijten, F.S.S.; Ferrier, C.H.; van Putten, Michel Johannes Antonius Maria; Zijlmans, M.; Huiskamp, G.J.M.

    Objective: Single Pulse Electrical Stimulation (SPES) probes epileptogenic cortex during electrocorticography. Two SPES responses are described: pathological delayed responses (DR, >100 ms) associated with the seizure onset zone (SOZ) and physiological early responses (ER, <100 ms) that map cortical

  12. 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.

  13. Inflammation marker, damage marker and anabolic hormone responses to resistance training with vascular restriction in older males.

    Science.gov (United States)

    Karabulut, Murat; Sherk, Vanessa D; Bemben, Debra A; Bemben, Michael G

    2013-09-01

    The goal of this study was to examine anabolic hormone, muscle damage marker and inflammation marker responses to two types of resistance training protocols in older men. Thirty-six healthy older males (mean age = 56.6 ± 0.6 years) completed 6 weeks of high-intensity resistance training (HI-RT), low-intensity resistance training with vascular restriction (LI-BFR) or no exercise control group (CON) three times per week. Three upper body exercises were performed by both exercise groups at the same intensity (at 80% 1-RM), but lower body exercises were performed by the HI-RT group at 80% 1-RM and by the LI-BFR group at 20% 1-RM with vascular restriction. Resting serum creatine kinase (CK), interleukin 6 (IL-6), insulin-like growth factor-I (IGF-I), IGF binding protein 3 (IGFBP-3) and testosterone (T) were measured before and after training. No significant group differences in resting CK, IL-6, IGF-I, IGFBP-3 and T were detected following training (P>0.05). In addition, there were no significant changes in muscle cross-sectional area (CSA), but a trend for significant decreases in the percent changes in thigh subcutaneous fat (P = 0.051). Although training-induced anabolic hormone response did not reach statistical significance, our findings on CK and IL-6 indicated that the LI-BFR training protocol was safe and well tolerated for older men to perform to improve muscular strength. © 2013 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

  14. Response of mesenchymal stem cells to shear stress in tissue-engineered vascular grafts

    Institute of Scientific and Technical Information of China (English)

    Jian-de DONG; Yong-quan GU; Chun-min LI; Chun-ren WANG; Zeng-guo FENG; Rong-xin QIU; Bing CHEN; Jian-xin LI; Shu-wen ZHANG; Zhong-gao WANG; Jian ZHANG

    2009-01-01

    Aim: Recent studies have demonstrated that mesenchymal stem cells (MSCs) can differentiate into endothelial cells. The effect of shear stress on MSC differentiation is incompletely understood, and most studies have been based on two-dimen-sional systems. We used a model of tissue-engineered vascular grafts (TEVGs) to investigate the effects of shear stress on MSC differentiation.Methods: MSCs were isolated from canine bone marrow. The TEVG was constructed by seeding MSCs onto poly-ε-caprolactone and lactic acid (PCLA) scaffolds and subjecting them to shear stress provided by a pulsatile bioreactor for four days (two days at 1 dyne/cm2 to 15 dyne/cm2 and two days at 15 dyne/cm2).Results: Shear stress significantly increased the expression of endothelial cell markers, such as platelet-endothelial cell adhesion molecule-1 (PECAM-1), VE-cadherin, and CD34, at both the mRNA and protein levels as compared with static control cells. Protein levels of alpha-smooth muscle actin (α-SMA) and calponin were substantially reduced in shear stress-cultured cells. There was no significant change in the expression of α-SMA, smooth muscle myosin heavy chain (SMMHC)or calponin at the mRNA level.Conclusion: Shear stress upregulated the expression of endothelial cell-related markers and downregulated smooth muscle-related markers in canine MSCs. This study may serve as a basis for further investigation of the effects of shear stress on MSC differentiation in TEVGs.

  15. Influence of altered blood rheology on ventricular-vascular response to exercise.

    Science.gov (United States)

    Sharman, James E; Brown, Joseph; Holland, David J; Macdonald, Graeme; Kostner, Karam; Marwick, Thomas H

    2009-11-01

    Blood (or plasma) rheology is related to cardiovascular risk. Mechanisms of this association are unclear but may be partially related to impaired left ventricular (LV) function and increased central blood pressure (BP) during light activity. This study aimed to test these hypotheses. Twenty patients (14 men; aged 61+/-12 years) with polycythemia rubra vera (n=16) or hemochromatosis (n=4) were studied at rest and during exercise at approximately 50% of maximal heart rate before and after venesection (500 mL; volume replaced with saline) to elicit an acute decrease in plasma viscosity at stable BP. Controls (n=20) underwent the same protocol with 25-mL venesection. Central BP and augmentation index were determined by tonometry. Resting LV systolic (peak longitudinal systolic strain rate and strain) and diastolic functions were determined by tissue-Doppler echocardiography. Venesection with blood volume replacement decreased viscosity (1.46+/-0.10 to 1.41+/-0.11 centipoise), protein, and hemoglobin (P0.10 for all). There was no change in LV diastolic function (P>0.12 for all). Exercise augmentation index in patients was reduced after venesection (24+/-12% to 17+/-9%; P=0.001) despite no significant change in other BP variables. Hemodynamics (resting or exercise) were not significantly changed in controls. Exercise central systolic BP correlated with triglycerides (r=0.59; P0.05). We conclude that an acute change in blood rheology improves ventricular-vascular interaction by enhanced LV systolic function and reduced light-exercise central BP.

  16. Cerebro vascular reactivity (CVR) of middle cerebral artery in response to CO2 5% inhalation in preeclamptic women.

    Science.gov (United States)

    Sariri, Elaheh; Vahdat, Mansoureh; Behbahani, Afsaneh Shariati; Rohani, Mohammad; Kashanian, Maryam

    2013-07-01

    To compare the cerebro vascular reactivity (CVR) of middle cerebral artery (MCA) in response to CO2 5% inhalation between preeclamptic and normotensive pregnant women, also, between mild and severe preeclampsia. A comparative study was performed on 61 women with preeclampsia and 65 normotensive pregnant women who were in the third trimester of gestation. MCA transcranial Doppler ultrasound was used to measure CVR in response to CO2 5% inhalation. Pulsatility index (PI), resistance index (RI), blood pressure, maternal age, gestational age and gravidity were also recorded. Baseline PI and RI were lower in the preeclamptic group (p < 0.05). Inhalation of CO2 5% caused significant increase in CVR among normotensive pregnant women in comparison with preeclamptic group (1.006 ± 0.229 versus 0.503 ± 0.209, p = 0.0001). Significantly, more cerebral vasodilatation was found among mild preeclamptic women in comparison with severe preeclamptic women (0.583 ± 0.193 versus 0.383 ± 0.173, p = 0.0001). The receiver operating characteristics curve analysis revealed acceptable difference between CO2 stimulation test of preeclamptic and normotensive women (Area under curve = 0.973, p = 0.0001). CVR in response to CO2 5% is less in preeclamptic pregnant women than normotensives, also, in severe preeclampsia, it is less than mild preeclampsia.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Early expressions of hypoxia-inducible factor 1alpha and vascular endothelial growth factor increase the neuronal plasticity of activated endogenous neural stem cells after focal cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Seung Song; Jong-Tae Park; Joo Young Na; Man-Seok Park; Jeong-Kil Lee; Min-Cheol Lee; Hyung-Seok Kim

    2014-01-01

    Endogenous neural stem cells become “activated” after neuronal injury, but the activation sequence and fate of endogenous neural stem cells in focal cerebral ischemia model are little known. We evaluated the relationships between neural stem cells and hypoxia-inducible fac-tor-1α and vascular endothelial growth factor expression in a photothromobotic rat stroke model using immunohistochemistry and western blot analysis. We also evaluated the chrono-logical changes of neural stem cells by 5-bromo-2′-deoxyuridine (BrdU) incorporation. Hypoxia-inducible factor-1α expression was initially increased from 1 hour after ischemic injury, followed by vascular endothelial growth factor expression. Hypoxia-inducible factor-1αimmunoreactivity was detected in the ipsilateral cortical neurons of the infarct core and peri-in-farct area. Vascular endothelial growth factor immunoreactivity was detected in bilateral cortex, but ipsilateral cortex staining intensity and numbers were greater than the contralateral cortex. Vascular endothelial growth factor immunoreactive cells were easily found along the peri-infarct area 12 hours after focal cerebral ischemia. The expression of nestin increased throughout the microvasculature in the ischemic core and the peri-infarct area in all experimental rats after 24 hours of ischemic injury. Nestin immunoreactivity increased in the subventricular zone during 12 hours to 3 days, and prominently increased in the ipsilateral cortex between 3-7 days. Nes-tin-labeled cells showed dual differentiation with microvessels near the infarct core and reactive astrocytes in the peri-infarct area. BrdU-labeled cells were increased gradually from day 1 in the ipsilateral subventricular zone and cortex, and numerous BrdU-labeled cells were observed in the peri-infarct area and non-lesioned cortex at 3 days. BrdU-labeled cells rather than neu-rons, were mainly co-labeled with nestin and GFAP. Early expressions of hypoxia-inducible factor-1α and

  19. 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

    2017-01-01

    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 pha

  20. The vascular response observation by the monitoring of the photosensitizer, oxygen, and blood flow during the high intensity pulsed excitation photodynamic therapy 1h after water-soluble photosensitizer intravenous injection

    Science.gov (United States)

    Hakomori, S.; Matsuo, H.; Arai, T.

    2008-02-01

    We investigated the correlation between the therapeutic effect by early irradiation Photodynamic Therapy (PDT) and vascular response. The early irradiation PDT has been proposed by our group. This PDT protocol is that pulse laser irradiates to tumors 1 h after intravenous injection of water-soluble photosensitizer. The intact layer appeared over the well treated layer, when the early irradiation PDT was performed at rat prostate subcutaneous tumors with high intensity pulse laser (over 1 MW/cm2 in peak intensity) and Talaporfin sodium. In order to clarify the phenomenon mechanism, we monitored blood volume, surface temperature, photosensitizer amount, and oxygen saturation during the PDT. The rat prostate subcutaneous tumor was irradiated with excimer dye laser light at 1 h after the intravenous injection. The photosensitizer dose wa 2.0 mg/kg, and the pulse energy density was 2.5 mJ/cm2 (low intensity) or 10 mJ/cm2 (high intensity). Under the low intensity pulsed PDT, the fluorescence amount was decreasing gently during the irradiation, and the blood volume and oxygen saturation started decreasing just after the irradiation. Under the hgh intensity pulsed PDT, the fluorescence amount was decreaased rapidly for 20 s after the irradiation started. The blood volume and oxygen saturation were temporally decreased during the irradiation, and recovered at 48 hrs after the irradiation. According to these results, under the low intensity pulsed PDT, the blood vessel located near the surface started closing just after the irradiation. On the other hand, under the high intensity pulsed PDT the blood vessel was closing for 20 s after the irradiation started, moreover, the blood flow recovered at 48 hrs after the irradiation. We concluded that the vascular response depended on the pulse energy density, and then the therapeutic effect was attributed to the difference of the vascular response. In other words, the surface intact layer could be considered to be induced the

  1. 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.

  2. Monitoring of the cardiac and vascular response to LBNP during the 14 day spaceflight "Cassiopee".

    Science.gov (United States)

    Arbeille, P h; Fomina, G; Sigaudo, D; Alferova, I; Porcher, M; Boulay, J; Gharib, C

    1997-07-01

    The objective of the present experiment was to monitor in real time the cardiac and the peripheral response to inflight LBNP. The second objective was to detect and quantify hemodynamic signs of orthostatic tolerance inflight by measuring the heart rate, blood pressure, cardiac and regional hemodynamics during LBNP.

  3. Sex differences in angiotensin II responses contribute to a differential regulation of cox-mediated vascular dysfunction during aging.

    Science.gov (United States)

    Costa, Gustavo; Garabito, Manel; Jiménez-Altayó, Francesc; Onetti, Yara; Sabate, Manel; Vila, Elisabet; Dantas, Ana Paula

    2016-12-01

    Aging is a cardiovascular risk factor partially related to activation of the Renin-Angiotensin System (RAS). RAS activation is also influenced by sex. In this regard, our study aims to determine whether sex-associated differences in RAS contribute to a differential regulation of vascular aging and associated dysfunction. Male and female outbreed CD-1 mice were studied at 3 and 12months of age (M). Contribution of RAS was determined by treating mice from 3M to 12M with the AngII type 1 receptor blocker losartan (0.6g/L in the drinking water). At 12M, contractions to AngII were higher in males compared to females (P<0.05). This effect was paralleled by a decrease in AngII type 2 receptors in 12M males. Aging also diminished ACh relaxation in males, but did not modify female responses. Treatment of aortas with indomethacin (10μM) restored the impaired endothelium-dependent relaxation in 12M males, suggesting an increase of cyclooxygenase (COX)-derived vasoconstrictors in aged males. Chronic treatment of mice with losartan also improved endothelium-dependent relaxation. Besides, losartan significantly decreased COX-2 expression and activity in 12M male, with a minor effect in aged females. Aging increases AngII contraction and induces endothelial dysfunction differently in males and females. In aged males, RAS contributed to increased COX-2 expression and activity, which in turn may lead to vascular dysfunction. Copyright © 2016 Elsevier Inc. All rights reserved.

  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 BACKGROUND: 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. RESULTS: 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. CONCLUSIONS: 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

  6. Connexin mimetic peptides fail to inhibit vascular conducted calcium responses in renal arterioles

    DEFF Research Database (Denmark)

    Sørensen, Charlotte Mehlin; Salomonsson, Max; Braunstein, Thomas Hartig;

    2008-01-01

    of mimetic peptides directed against one or more connexins. Preglomerular resistance vessels were microdissected from kidneys of Sprague-Dawley rats and loaded with fura 2. The vessels were stimulated locally by applying electrical current through a micropipette, and the conducted calcium response...... was measured 500 mum from the site of stimulation. Application of connexin mimetic peptides directed against Cx40, 37/43, 45, or a cocktail with equimolar amounts of each, did not inhibit the propagated response, whereas the nonselective gap junction uncoupler carbenoxolone completely abolished the propagated...... mimetic peptides directed against Cx40, 37/43, or 45. Further studies are needed to determine whether conducted vasoconstriction is mediated via previously undescribed pathways....

  7. Effects of chloride channel blockers on rat renal vascular responses to angiotensin II and norepinephrine

    DEFF Research Database (Denmark)

    Steendahl, Joen; Sørensen, Charlotte Mehlin; Salomonsson, Max;

    2003-01-01

    preglomerular vessels caused a prompt increase in [Ca2+]i. Renal preinfusion of DIDS (0.6 and 1.25 micromol/min) attenuated the ANG II-induced vasoconstriction to approximately 35% of the control response, whereas the effects of NE were unaltered. Niflumic acid (0.14 and 0.28 micromol/min) and 2......-[(2-cyclopentenyl-6,7-dichloro-2,3-dihydro-2-methyl-1-oxo-1H-inden-5-yl)oxy]acetic acid (IAA-94; 0.045 and 0.09 micromol/min) did not affect the vasoconstrictive responses of these compounds. Pretreatment with niflumic acid (50 microM) or IAA-94 (30 microM) for 2 min decreased baseline [Ca2+]i but did not change...

  8. Effects of tempol on altered metabolism and renal vascular responsiveness in fructose-fed rats.

    Science.gov (United States)

    Abdulla, Mohammed H; Sattar, Munavvar A; Johns, Edward J

    2016-02-01

    This study investigated the effect of tempol (a superoxide dismutase mimetic) on renal vasoconstrictor responses to angiotensin II (Ang II) and adrenergic agonists in fructose-fed Sprague-Dawley rats (a model of metabolic syndrome). Rats were fed 20% fructose in drinking water (F) for 8 weeks. One fructose-fed group received tempol (FT) at 1 mmol·L(-1) in drinking water for 8 weeks or as an infusion (1.5 mg·kg(-1)·min(-1)) intrarenally. At the end of the treatment regimen, the renal responses to noradrenaline, phenylephrine, methoxamine, and Ang II were determined. F rats exhibited hyperinsulinemia, hyperuricemia, hypertriglyceridemia, and hypertension. Tempol reduced blood glucose and insulin levels (all p fructose-fed rats.

  9. Polymorphisms in vascular endothelial growth factor receptor 2 are associated with better response rates to ranibizumab treatment in age-related macular degeneration

    NARCIS (Netherlands)

    Hermann, M.M.; Asten, F. van; Muether, P.S.; Smailhodzic, D.; Lichtner, P.; Hoyng, C.B.; Kirchhof, B.; Grefkes, C.; Hollander, A.I. den; Fauser, S.

    2014-01-01

    PURPOSE: Intravitreal anti-vascular endothelial growth factor (VEGF) injections are currently the standard treatment for neovascular age-related macular degeneration (AMD), but a broad range of response rates has been observed. We evaluated the association of single nucleotide polymorphisms (SNPs) i

  10. [Vascular factors in glaucoma].

    Science.gov (United States)

    Mottet, B; Aptel, F; Geiser, M; Romanet, J P; Chiquet, C

    2015-12-01

    The exact pathophysiology of glaucoma is not fully understood. Understanding of the vascular pathophysiology of glaucoma requires: knowing the techniques for measuring ocular blood flow and characterizing the topography of vascular disease and the mechanisms involved in this neuropathy. A decreased mean ocular perfusion pressure and a loss of vascular autoregulation are implicated in glaucomatous disease. Early decrease in ocular blood flow has been identified in primary open-angle glaucoma and normal pressure glaucoma, contributing to the progression of optic neuropathy. The vascular damage associated with glaucoma is present in various vascular territories within the eye (from the ophthalmic artery to the retina) and is characterized by a decrease in basal blood flow associated with a dysfunction of vasoregulation.

  11. Systemic responses in a tolerant olive (Olea europaea L. cultivar upon root colonization by the vascular pathogen Verticillium dahliae

    Directory of Open Access Journals (Sweden)

    Carmen Gómez-Lama Cabanás

    2015-09-01

    Full Text Available Verticillium wilt of olive (VWO is caused by the vascular pathogen Verticillium dahliae. One of the best VWO management measures is the use of tolerant cultivars; however, our knowledge on VWO tolerance/resistance genetics is very limited. A transcriptomic analysis was conducted to (i identify systemic defence responses induced/repressed in aerial tissues of the tolerant cultivar Frantoio upon root colonization by V. dahliae, and (ii determine the expression pattern of selected defence genes in olive cultivars showing differential susceptibility to VWO. Two suppression subtractive hybridization cDNA libraries, enriched in up-regulated (FU and down-regulated (FD genes respectively, were generated from ‘Frantoio’ aerial tissues. Results showed that broad systemic transcriptomic changes are taking place during V. dahliae-‘Frantoio’ interaction. A total of 585 FU and 381 FD unigenes were identified, many of them involved in defence response to (abiotic stresses. Selected genes were then used to validate libraries and evaluate their temporal expression pattern in ‘Frantoio’. Four defence genes were analyzed in cultivars Changlot Real (tolerant and Picual (susceptible. An association between GRAS1 and DRR2 gene expression patterns and susceptibility to VWO was observed, suggesting that these transcripts could be further evaluated as markers of the tolerance level of olive cultivars to V. dahliae.

  12. 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 .

  13. Vascular endothelial growth factor before and after locoregional treatment and its relation to treatment response in hepatocelluar carcinoma patients

    Institute of Scientific and Technical Information of China (English)

    Heba Sedrak; Noaman El-Garem; Mervat Naguib; Heba El-Zawahry; Mohamed Esmat; Lila Rashed

    2015-01-01

    Objective: To evaluate vascular endothelial growth factor (VEGF) levels in hepatocel-lular carcinoma patients before and after transcatheter arterial chemoembolization (TACE) and percutaneous ethanol injection (PEI) and its relation to treatment response. Methods: A total of 40 patients with unrespectable hepatocelluar carcinoma were assessed clinically. Twenty patients were suitable to be treated by TACE, while other 20 patients were treated with PEI. Serum VEGF levels were measured before and 1 month after each procedure by ELISA. Response was assessed after 1 month according to Union Internationale Contre le Cancer evaluation criteria based on change in tumor size as measured by ultrasound. Results: There was no significant difference between TACE and PEI groups with regard to age, sex, tumor size, response to local therapy, or VEGF and alpha-fetoprotein before and after therapy. VEGF levels after TACE were significantly higher than before TACE [(298.1 ± 123.6) pg/mL vs. (205.8 ± 307.3) pg/mL;P=0.001]. Also, VEGF levels were significantly higher after PEI than before PEI [(333.8 ± 365.6) pg/mL vs. (245.3 ± 301.8) pg/mL;P=0.000]. Non-responders of both groups had significantly high VEGF levels than responder's, both before [(985.0 ± 113.2) pg/mL vs. (117.1 ± 75.3) pg/mL;P Conclusions: Both TACE and PEI were associated with an increase in serum VEGF in hepatocelluar carcinoma patients. Higher levels of VEGF before and after therapy were found in non-responders, suggesting that VEGF is a useful marker in predicting treatment response.

  14. Does Early Responsive Parenting Have a Special Importance for Children's Development or Is Consistency across Early Childhood Necessary?

    Science.gov (United States)

    Landry, Susan H.; Smith, Karen E.; Swank, Paul R.; Assel, Mike A.; Vellet, Sonya

    2001-01-01

    Examined the role of early versus ongoing maternal responsiveness in predicting cognitive and social development for full-term and preterm children (low- and high-risk) at five ages. Found that children, especially preterm children, showed faster cognitive growth when mothers were consistently responsive. Social growth was similar in the…

  15. GENETIC VARIATION IN THE ALPHA1B - ADRENERGIC RECEPTOR AND VASCULAR RESPONSE

    Science.gov (United States)

    Adefurin, Abiodun; Ghimire, Laxmi V.; Kohli, Utkarsh; Muszkat, Mordechai; Sofowora, Gbenga G.; Li, Chun; Levinson, Rebecca T.; Paranjape, Sachin Y.; Stein, C. Michael; Kurnik, Daniel

    2016-01-01

    α1B- adrenergic receptors contribute to vasoconstriction in humans. We tested the hypothesis that variation in the ADRA1B gene contributes to interindividual variability and ethnic differences in adrenergic vasoconstriction. We measured dorsal hand vein responses to increasing doses of phenylephrine in 64 Caucasians and 41 African-Americans and genotyped 34 ADRA1B variants. We validated findings in another model of catecholamine-induced vasoconstriction, the increase in mean arterial pressure (ΔMAP) during a cold pressor test (CPT). One ADRA1B variant, rs10070745, present in 14 African-American heterozygotes but not in Caucasians, was associated with a lower phenylephrine ED50 (geometric mean [95% CI], 144 [69–299] ng/ml) compared to 27 African-American non-carriers (208 [130–334] ng/ml; P=0.015) and contributed to the ethnic differences in ED50. The same variant was also associated with a greater ΔMAP during CPT (P=0.008). In conclusion, ADRA1B rs10070745 was significantly associated with vasoconstrictor responses after adrenergic stimulation and contributed to the ethnic difference in phenylephrine sensitivity. PMID:27089938

  16. Vascular Diseases

    Science.gov (United States)

    The vascular system is the body's network of blood vessels. It includes the arteries, veins and capillaries that carry ... to and from the heart. Problems of the vascular system are common and can be serious. Arteries ...

  17. Vascular Effects of Histamine

    African Journals Online (AJOL)

    olayemitoyin

    effects of histamine are mediated via H1 and H2 receptors and the actions are modulated by H3 receptor subtype ... Keywords: Histamine, Vascular smooth muscle, Endothelium .... responses to histamine, but not those to acetylcholine, were.

  18. Early skin toxicity predicts better outcomes, and early tumor shrinkage predicts better response after cetuximab treatment in advanced colorectal cancer.

    Science.gov (United States)

    Kogawa, T; Doi, A; Shimokawa, M; Fouad, T M; Osuga, T; Tamura, F; Mizushima, T; Kimura, T; Abe, S; Ihara, H; Kukitsu, T; Sumiyoshi, T; Yoshizaki, N; Hirayama, M; Sasaki, T; Kawarada, Y; Kitashiro, S; Okushiba, S; Kondo, H; Tsuji, Y

    2015-03-01

    Cetuximab-containing treatments for metastatic colorectal cancer have been shown to have higher overall response rates and longer progression-free and overall survival than other systemic therapies. Cetuximab-related manifestations, including severe skin toxicity and early tumor shrinkage, have been shown to be predictors of response to cetuximab. We hypothesized that early skin toxicity is a predictor of response and better outcomes in patients with advanced colorectal carcinoma. We retrospectively evaluated 62 patients with colorectal adenocarcinoma who had unresectable tumors and were treated with cetuximab in our institution. Skin toxicity grade was evaluated on each treatment day. Tumor size was evaluated using computed tomography prior to treatment and 4-8 weeks after the start of treatment with cetuximab.Patients with early tumor shrinkage after starting treatment with cetuximab had a significantly higher overall response rate (P = 0.0001). Patients with early skin toxicity showed significantly longer overall survival (P = 0.0305), and patients with higher skin toxicity grades had longer progression-free survival (P = 0.0168).We have shown that early tumor shrinkage, early onset of skin toxicity, and high skin toxicity grade are predictors of treatment efficacy and/or outcome in patients with advanced colorectal carcinoma treated with cetuximab.

  19. Vascular Vertigo

    OpenAIRE

    Mazyar Hashemilar; Masoud Nikanfar; Dariush Savadi Oskoui

    2017-01-01

    Vertigo is a common complaint in neurology and medicine. The most common causes of vertigo are benign paroxysmal positional vertigo, vestibular neuritis, Meniere’s disease, and vascular disorders. Vertigo of vascular origin is usually limited to migraine, transient ischemic attacks, and ischemic or hemorrhagic stroke. Vascular causes lead to various central or peripheral vestibular syndromes with vertigo. This review provides an overview of epidemiology and clinical syndromes of vascular vert...

  20. Elevation of iron storage in humans attenuates the pulmonary vascular response to hypoxia.

    Science.gov (United States)

    Bart, Nicole K; Curtis, M Kate; Cheng, Hung-Yuan; Hungerford, Sara L; McLaren, Ross; Petousi, Nayia; Dorrington, Keith L; Robbins, Peter A

    2016-08-01

    Sustained hypoxia over several hours induces a progressive rise in pulmonary artery systolic pressure (PASP). Administration of intravenous iron immediately prior to the hypoxia exposure abrogates this effect, suggesting that manipulation of iron stores may modify hypoxia-induced pulmonary hypertension. Iron (ferric carboxymaltose) administered intravenously has a plasma half-life of 7-12 h. Thus any therapeutic use of intravenous iron would require its effect on PASP to persist long after the iron-sugar complex has been cleared from the blood. To examine this, we studied PASP during sustained (6 h) hypoxia on 4 separate days (days 0, 1, 8, and 43) in 22 participants. On day 0, the rise in PASP with hypoxia was well matched between the iron and saline groups. On day 1, each participant received either 1 g of ferric carboxymaltose or saline in a double-blind manner. After administration of intravenous iron, the rise in PASP with hypoxia was attenuated by ∼50%, and this response remained suppressed on both days 8 and 43 (P iron, values for ferritin concentration, transferrin saturation, and hepcidin concentration rose significantly (P iron stores persists long after the artificial iron-sugar complex has been eliminated from the blood. The persistence of this effect suggests that intravenous iron may be of benefit in some forms of pulmonary hypertension.

  1. Skin barrier function in healthy volunteers as assessed by transepidermal water loss and vascular response to hexyl nicotinate: intra- and inter-individual variability.

    Science.gov (United States)

    Oestmann, E; Lavrijsen, A P; Hermans, J; Ponec, M

    1993-02-01

    This study assesses the variability of two non-invasive methods of measuring stratum corneum barrier function in vivo. Transepidermal water loss (TEWL), and the vascular response to hexyl nicotinate (HN) penetration as determined by laser-Doppler flowmetry, were measured in a group of 21 healthy volunteers. Each time profile of the vascular response to HN penetration was analysed using the following parameters: the baseline cutaneous blood flow, the lag-time between application and initial response (t0), the time between application and maximum response (tmax), the maximum response, and the slope of the curve. TEWL measured on the left volar forearm showed a normal range of 3.9-7.6 g/m2h and a small inter-individual variability [coefficient of variation (CV) 19.4%]. TEWL values at three other forearm sites did not show differences of clinical importance compared with the left volar forearm. The parameters of the vascular response to HN penetration spanned a wider normal range than the TEWL values (CV between 33 and 52%). Repeat measurements after a 1-2 month interval showed highly reproducible individual TEWL values. The mean difference between first and second measurements was only 0.03 g/m2h; the relative difference 0.6%. The intra-individual reproducibility of t0 and tmax. for HN penetration was also high (relative differences of 2.8 and 3.1%, respectively). The other vascular response parameters were less reproducible (relative differences of 6.9-18.6%). We conclude that TEWL and selected parameters of HN penetration, as non-invasive tests of the stratum corneum barrier function, yield reproducible results and are hence useful for investigations assessing the skin barrier function in various disorders.

  2. 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.)

  3. 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.

  4. Effect of Circular ANRIL on the Inflammatory Response of Vascular Endothelial Cells in a Rat Model of Coronary Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Chun-Li Song

    2017-07-01

    Full Text Available Background/Aims: This study aims to investigate the role of circular antisense non-coding RNA at the INK4 locus (cANRIL in the inflammatory response of vascular endothelial cells (ECs in a rat model of coronary atherosclerosis (AS. A rat model of AS was established with rats that were injected with a large dose of vitamin D3 and fed a high-fat diet. Methods: Sixty Wistar rats were randomly assigned into control, model, empty vector, over-expressed cANRIL and low-expressed cANRIL groups (12 rats in each group. Sixteen weeks later, the ultrastructure of their coronary arteries was observed via transmission electron microscopy. Rat serum lipid levels were analyzed using an automatic biochemical analyzer, and their atherogenic index (AI values were calculated. Hematoxylin and eosin staining was used to observe the endothelial morphology of rats. Additionally, rat EC apoptosis was tested via a TUNEL assay. Enzyme-linked immunosorbent assays (ELISAs were applied to measure serum levels of interleukin-1 (IL-1, IL-6, matrix metalloproteinase-9 (MMP-9 and C-reactive protein (CRP. The cANRIL, Bax, bcl-2 and caspase-3 mRNA expression levels were measured with a quantitative real-time polymerase chain reaction (qRT-PCR. The protein expression levels of Bax, bcl-2 and caspase-3 were detected using immunohistochemistry. Results: In the control group, ECs were closely arranged with normal structures, and there was no proliferation. In the model, empty vector and over-expressed cANRIL groups, some cells were not present, and atherosclerotic plaques and thrombi appeared. However, in the under-expressed cANRIL group, the cells had a normal structure. Compared with the model and empty vector groups, the levels of total cholesterol (CHOL, triglycerides (TGs, low density lipoprotein (LDL, IL-1, IL-6, MMP-9, CRP, cANRIL, Bax, and caspase-3, AI values, and rates of EC apoptosis decreased in the low-expressed cANRIL group, while HDL (high density lipoprotein levels and

  5. The use of plasma-activated covalent attachment of early domains of tropoelastin to enhance vascular compatibility of surfaces.

    Science.gov (United States)

    Hiob, Matti A; Wise, Steven G; Kondyurin, Alexey; Waterhouse, Anna; Bilek, Marcela M; Ng, Martin K C; Weiss, Anthony S

    2013-10-01

    All current metallic vascular prostheses, including stents, exhibit suboptimal biocompatibility. Improving the re-endothelialization and reducing the thrombogenicity of these devices would substantially improve their clinical efficacy. Tropoelastin (TE), the soluble precursor of elastin, mediates favorable endothelial cell interactions while having low thrombogenicity. Here we show that constructs of TE corresponding to the first 10 ("N10") and first 18 ("N18") N-terminal domains of the molecule facilitate endothelial cell attachment and proliferation equivalent to the performance of full-length TE. This N-terminal ability contrasts with the known role of the C-terminus of TE in facilitating cell attachment, particularly of fibroblasts. When immobilized on a plasma-activated coating ("PAC"), N10 and N18 retained their bioactivity and endothelial cell interactive properties, demonstrating attachment and proliferation equivalent to full-length TE. In whole blood assays, both N10 and N18 maintained the low thrombogenicity of PAC. Furthermore, these N-terminal constructs displayed far greater resistance to protease degradation by blood serine proteases kallikrein and thrombin than did full-length TE. When immobilized onto a PAC surface, these shorter constructs form a modified metal interface to establish a platform technology for biologically compatible, implantable cardiovascular devices.

  6. Soluble fms-like tyrosine kinase-1 and vascular endothelial growth factor:Novel markers for unexplained early recurrent pregnancy loss

    Institute of Scientific and Technical Information of China (English)

    Mahmoud Fathy; Hassan

    2014-01-01

    Objective:To evaluate the role of soluble fms-like tyrosine kinase-1(sFlt-1) and vascular endothelial growth factor(VEGF) for prediction of pregnancy loss in patients with history of unexplained early recurrent pregnancy loss(RPL).Methods:A prospective case control study was conducted in42 women with history of unexplained earlyRPL, and170 pregnant controls with history of uncomplicated pregnancy.We measured maternal serum sFlt-1 andVEGF at gestational age6-9 weeks as predictor for pregnancy loss.Results:Mean serum levels of sFlt-1 andVEGF were significantly higher inRPL group than controls(10439.7±385.4vs3304.5±104.8;P<0.0001, for sFlt-1, and1885.0±98.3 vs709.8±24.8;P<0.0001, forVEGF).Receiver operating characteristic(ROC) curves analyses established that sFlt-1 andVEGF were able to discriminate women at risk of developing pregnancy loss with area underROC curve0.970 for sFlt-1 and0.953 forVEGF.Cutoff value of5159.5 pg/mL for sFlt-1 was predictor for early pregnancy loss with 95.2% sensitivity,91.2% specificity, and odds ratio(OR)206 [95%confidence interval(CI),45.4-941].Cutoff value of915.5 pg/mL forVEGF was predictor for early pregnancy loss with92.9% sensitivity,90.6% specificity, andOR125 [95%CI:34.7-451].Conclusion:These data advocate a relationship between sFlt-1,VEGF, andRPL suggesting that the high levels of sFlt-1 andVEGF might be associated with the pathogenesis ofRPL.

  7. 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.

  8. 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.

  9. A prospective, comparative study on the early effects of local and remote radiation therapy on carotid intima-media thickness and vascular cellular adhesion molecule-1 in patients with head and neck and prostate tumors.

    Science.gov (United States)

    Pereira Lima, Marta N; Biolo, Andréia; Foppa, Murilo; da Rosa, Priscila Raupp; Rohde, Luis Eduardo P; Clausell, Nadine

    2011-12-01

    To investigate early vascular changes related to carotid atherosclerotic injury post-radiation therapy (RT), we studied carotid intima-media thickness (IMT) and vascular cellular adhesion molecule (VCAM)-1 at two time-points after RT and compared local and remote irradiation effects in patients with head and neck (HNC) and prostate cancer (PC), respectively. We prospectively studied patients beginning RT for HNC or PC, performing carotid ultrasound before RT, early after and six months after treatment to measure carotid IMT. Blood samples were simultaneously collected to study VCAM-1 by ELISA. We studied 19 patients with HNC and 24 with PC. Patients with HNC were younger (55 ± 10 years) than PC patients (68 ± 8 years). Early post-RT only HNC patients had an increase in IMT compared to baseline measurements (0.73 ± 0.04 mm vs. 0.80 ± 0.05 mm, p=0.029). On the other hand, VCAM-1 levels decreased in PC patients, remaining unchanged in HNC patients. Late post-RT (six months from previous assessment), neither IMT nor VCAM-1 values changed in both groups. Local and remote RT seem to exert differential early effects regarding vascular-related changes: (1) local RT seems to affect vascular structure and increase IMT and (2) RT for PC is associated with reduction in VCAM levels, suggesting systemic modulation of cancer-related factors. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  10. Intrauterine endotoxin-induced impairs pulmonary vascular function and right ventricular performance in infant rats and improvement with early vitamin D therapy.

    Science.gov (United States)

    Mandell, Erica; Powers, Kyle N; Harral, Julie W; Seedorf, Gregory J; Hunter, Kendall S; Abman, Steven H; Dodson, R Blair

    2015-12-15

    High pulmonary vascular resistance (PVR), proximal pulmonary artery (PA) impedance, and right ventricular (RV) afterload due to remodeling contribute to the pathogenesis and severity of pulmonary hypertension (PH). Intra-amniotic exposure to endotoxin (ETX) causes sustained PH and high mortality in rat pups at birth, which are associated with impaired vascular growth and RV hypertrophy in survivors. Treatment of ETX-exposed pups with antenatal vitamin D (vit D) improves survival and lung growth, but the effects of ETX exposure on RV-PA coupling in the neonatal lung are unknown. We hypothesized that intrauterine ETX impairs RV-PA coupling through sustained abnormalities of PA stiffening and RV performance that are attenuated with vit D therapy. Fetal rats were exposed to intra-amniotic injections of ETX, ETX+vit D, or saline at 20 days gestation (term = 22 days). At postnatal day 14, pups had pressure-volume measurements of the RV and isolated proximal PA, respectively. Lung homogenates were assayed for extracellular matrix (ECM) composition by Western blot. We found that ETX lungs contain decreased α-elastin, lysyl oxidase, collagen I, and collagen III proteins (P < 0.05) compared control and ETX+vit D lungs. ETX-exposed animals have increased RV mechanical stroke work (P < 0.05 vs. control and ETX+vit D) and elastic potential energy (P < 0.05 vs. control and ETX+vit D). Mechanical stiffness and ECM remodeling are increased in the PA (P < 0.05 vs. control and ETX+vit D). We conclude that intrauterine exposure of fetal rats to ETX during late gestation causes persistent impairment of RV-PA coupling throughout infancy that can be prevented with early vit D treatment.

  11. Investigating Early Years Teachers' Understanding and Response to Children's Preconceptions

    Science.gov (United States)

    Kambouri, Maria

    2016-01-01

    This paper focuses on young children's scientific preconceptions and discusses teachers' identification of these preconceptions when teaching science in the early years, on which research is still limited. This paper is based on the theoretical framework of constructivism and it defines preconceptions as children's erroneous concepts prior to…

  12. 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...

  13. Alcohol Expectancy Responses from Teenagers: The Early Forewarning Signals

    OpenAIRE

    B., Sandhya; B.M.S., Carol; M.S., Kotian; B, Ganaraja

    2013-01-01

    Background: The Indian population is overwhelmed by the rapid developmental activities in the new millennium. This has brought in urbanization and several banes of the faster life. Alcoholism is one among the menaces which have to be tackled at an early stage.

  14. Singaporean Early Childhood Teachers' Responses to Myths about Child Abuse

    Science.gov (United States)

    Briggs, Freda; Potter, Gillian K.

    2004-01-01

    Prior to attending seminars on child abuse and domestic violence, 86 kindergarten and 64 special education (early childhood) teachers completed a questionnaire seeking views relating to the accuracy of statements relating to all forms of child abuse. This was designed to identify the accuracy of teachers' knowledge of child abuse and neglect…

  15. 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 ... foundation for the development of healthy eating behaviour and optimal skills for self-regulation and self-control of food intake. ... to verbal cues and contingencies which are appropriate ..... ethnicity may play a role in the feeding style adopted by.

  16. 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

    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......) years of age were included. Before training, leg blood flow, O2 delivery, O2 uptake, and lactate release during knee-extensor exercise were similar in pre- and postmenopausal women. Exercise training reduced (P heart...... rate during the same absolute workloads in the postmenopausal women. These effects were not detected in the premenopausal women. Quadriceps muscle protein contents of mitochondrial complex II, III, and IV, endothelial nitric oxide synthase (eNOS), cyclooxygenase-1 (COX.1), COX-2, and oestrogen related...

  17. Helicobacter pylori Antigens Inducing Early Immune Response in Infants.

    Science.gov (United States)

    Seo, Ji Hyun; Youn, Jong Hyuk; Kim, Eun A; Jun, Jin Su; Park, Ji Sook; Yeom, Jung Sook; Lim, Jae Young; Woo, Hyang Ok; Youn, Hee Shang; Ko, Gyung Hyuck; Park, Jin Sik; Baik, Seung Chul; Lee, Woo Kon; Cho, Myung Je; Rhee, Kwang Ho

    2017-07-01

    To identify the Helicobacter pylori antigens operating during early infection in sera from infected infants using proteomics and immunoblot analysis. Two-dimensional (2D) large and small gel electrophoresis was performed using H. pylori strain 51. We performed 2D immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM) antibody immunoblotting using small gels on sera collected at the Gyeongsang National University Hospital from 4-11-month-old infants confirmed with H. pylori infection by pre-embedding immunoelectron microscopy. Immunoblot spots appearing to represent early infection markers in infant sera were compared to those of the large 2D gel for H. pylori strain 51. Corresponding spots were analyzed by matrix-assisted laser desorption/ionization time of flight-mass spectrometry (MALDI-TOF-MS). The peptide fingerprints obtained were searched in the National Center for Biotechnology Information (NCBI) database. Eight infant patients were confirmed with H. pylori infection based on urease tests, histopathologic examinations, and pre-embedding immunoelectron microscopy. One infant showed a 2D IgM immunoblot pattern that seemed to represent early infection. Immunoblot spots were compared with those from whole-cell extracts of H. pylori strain 51 and 18 spots were excised, digested in gel, and analyzed by MALDI-TOF-MS. Of the 10 peptide fingerprints obtained, the H. pylori proteins flagellin A (FlaA), urease β subunit (UreB), pyruvate ferredoxin oxidoreductase (POR), and translation elongation factor Ts (EF-Ts) were identified and appeared to be active during the early infection periods. These results might aid identification of serological markers for the serodiagnosis of early H. pylori infection in infants. © 2017 The Korean Academy of Medical Sciences.

  18. Vascular endothelial growth factor receptor inhibitor SU5416 suppresses lymphocyte generation and immune responses in mice by increasing plasma corticosterone.

    Directory of Open Access Journals (Sweden)

    Jamison J Grailer

    Full Text Available Inhibitors of vascular endothelial growth factor and its receptors (VEGFRs are attractive therapeutic candidates for cancer treatment. One such small molecule VEGFR inhibitor, SU5416, limits angiogenesis in vivo and is widely used for investigating VEGFR signaling in tumor pathophysiology. Herein, we describe novel actions of SU5416 on the immune system. Treatment of mice with SU5416 for 3 days induced significant reductions in size and cellularity of peripheral lymph nodes. Interestingly, SU5416 did not affect initial lymphocyte localization to peripheral lymph nodes but did reduce lymphocyte accumulation during long-term migration assays. Treatment with SU5416 also induced severe loss of double-positive thymocytes resulting in thymic atrophy and a reduction in peripheral B cells. Furthermore, immune responses following immunization were reduced in mice treated with SU5416. Findings of thymic atrophy and reduced weight gain during SU5416 treatment suggested elevated corticosterone levels. Indeed, a significant 5-fold increase in serum corticosterone was found 4 hours after treatment with SU5416. Importantly, adrenalectomy negated the effects of SU5416 treatment on primary immune tissues, and partial reversal of SU5416-induced changes was observed following blockade of glucocorticoid receptors. SU5416 has been reported to inhibit the activation of latent transforming growth factor (TGF-β, a cytokine involved in the regulation of glucocorticoid release by the adrenal glands. Interestingly, treatment with a TGF-β receptor inhibitor, showed a similar phenotype as SU5416 treatment, including elevated serum corticosterone levels and thymic atrophy. Therefore, these results suggest that SU5416 induces glucocorticoid release directly from the adrenal glands, possibly by inhibition of TGF-β activation.

  19. Decreased heart rate variability responses during early postoperative mobilization

    DEFF Research Database (Denmark)

    Jans, Øivind; Brinth, Louise; Kehlet, Henrik

    2015-01-01

    to postoperative autonomic dysfunction. Thus, based on a previous study on haemodynamic responses during mobilization before and after elective total hip arthroplasty (THA), we performed secondary analyses of heart rate variability (HRV) and aimed to identify possible abnormal postoperative autonomic responses...

  20. 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 ...

  1. Outcome of poor response Paediatric AML using early SCT

    DEFF Research Database (Denmark)

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

    2013-01-01

    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......) 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...

  2. Experimental and numerical investigation on the transient vascular thermal response to multi-pulse Nd:YAG laser.

    Science.gov (United States)

    Li, Dong; Li, Ruohui; Jia, Hao; Chen, Bin; Wu, Wenjuan; Ying, Zhaoxia

    2017-06-09

    Port wine stains (PWS) are congenital vascular malformations that progressively darken and thicken with age. Laser therapy is currently the most effective way in clinical practice for PWS. A 1,064 nm Nd:YAG laser in the near-infrared band can achieve a deeper treatment depth compared to the current widely adopted pulsed dye laser. However, because of its relatively weak absorption by blood, single-pulse Nd:YAG laser requires high energy density to cause effective vessel damage, but may inflict undesirable burning to surrounding collagen. Multi-pulse laser has great potential in clinical treatment because it needs less energy density for each pulse. This paper presented an experimental and theoretical study of the transient thermal effects of low-energy multi-pulse Nd:YAG laser on blood vessels. In vivo experiments were performed on dorsal skin chamber. By using a high speed camera (up to 2,000 fps), the complete and dynamic thermal response of blood vessels during laser irradiation and between pulse intervals was obtained. In vitro experiment in capillary tubes and Numerical simulations by two-scale heat transfer model were also conducted to further explore the in vivo experimental findings. The complete and dynamic response of blood vessels were obtained, including vessel dilation, thrombus formation, partial vessel constriction, thread-like constriction, cavitation and bubbles, and hemorrhage. Thread-like constriction is the desirable treatment end point, which will only occur after thrombus completely occludes the vessel lumen. Cavitation can cause hemorrhage when thrombus fails to occlude the vessel lumen. In vitro experiment found that vessel constriction was due to the constriction of thrombus induced by laser irradiation. Theoretical investigation revealed that the mechanism for the effective reduction of energy density by multi-pulse Nd:YAG laser was due to enhanced light absorption of the blood with thrombus formation. For multi-pulse treatment, laser

  3. Turnbull - Early Detection and Rapid Response Team 2007

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Biocontrol agents and chemicals to facilitate the rapid response phase of the project will be purchased and applied and a Washington Service Corps AmeriCorps member...

  4. Turnbull - Early Detection and Rapid Response Team 2008

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Funding from this grant will allow for the purchase of biocontrol agents and chemicals to facilitate the rapid response phase of the project and to provide match for...

  5. Turnbull - Early Detection and Rapid Response Team 2010

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Funding from this grant will allow for the purchase of biocontrol agents and chemicals to facilitate the rapid response phase of the project and to provide funds to...

  6. What Is Vascular Disease?

    Science.gov (United States)

    ... Donors Corporate Sponsors Donor Privacy Policy What Is Vascular Disease? What Is Vascular Disease? Vascular disease is any abnormal condition of ... steps to prevent vascular disease here. Understanding the Vascular System Your vascular system – the highways of the ...

  7. MRI evaluation of vascular dementia

    Institute of Scientific and Technical Information of China (English)

    Yicheng Liu; Hongxing Zhang; Wei Huang; Wenjun Wan; Hongfen Peng

    2006-01-01

    OBJECTTVE: To explain the association between vascular dementia and the cranial MRI manifestations, and recognize the value of cranial MRI in the early diagnosis of vascular dementia and the assessment of disease conditions.DATA SOURCES: Pubmed database was searched to identify articles about the cranial MRI manifestations of patients with vascular dementia published in English from January 1992 to June 2006 by using the key words of "MRI, vascular dementia". Others were collected by searching the name of journals and title of articles in the Chinese full-text journal database.STUDY SELECTTON: The collected articles were primarily checked, those correlated with the cranial MRI manifestations of patients with vascular dementia were selected, while the obviously irrelative ones were excluded, and the rest were retrieved manually, the full-texts were searched.DATA EXTRACTION: Totally 255 articles were collected, 41 of them were involved, and the other 214 were excluded.DATA SYNTHESIS: MRI can be taken as one of the effective methods for the early diagnosis and disease evaluation of vascular dementia. White matter lesions are the important risk factors of vascular dementia.Vascular dementia is accompanied by the atrophy of related brain sites, but further confirmation is needed to investigate whether there is significant difference. MRI can be used to quantitatively investigate the infarcted sites and sizes of patients with vascular dementia after infarction, but there is still lack of systematic investigation on the association of the infarcted sites and sizes with the cognitive function of patients with vascular dementia.CONCLUSTON: Cranial MRI can detect the symptoms of vascular dementia at early period, so that corresponding measures can be adopted to prevent and treat vascular dementia in time.

  8. [Vascular dementia

    NARCIS (Netherlands)

    Leeuw, H.F. de; Gijn, J. van

    2004-01-01

    Vascular dementia is one of the most frequently occurring dementia syndromes. Its prevalence is about 5% among subjects above 85 years of age. Elevated blood pressure and atherosclerosis are the most important risk factors. According to international criteria, vascular dementia usually occurs within

  9. Cellular Immune Responses and Viral Diversity in Individuals Treated during Acute and Early HIV-1 Infection

    Science.gov (United States)

    Altfeld, Marcus; Rosenberg, Eric S.; Shankarappa, Raj; Mukherjee, Joia S.; Hecht, Frederick M.; Eldridge, Robert L.; Addo, Marylyn M.; Poon, Samuel H.; Phillips, Mary N.; Robbins, Gregory K.; Sax, Paul E.; Boswell, Steve; Kahn, James O.; Brander, Christian; Goulder, Philip J.R.; Levy, Jay A.; Mullins, James I.; Walker, Bruce D.

    2001-01-01

    Immune responses induced during the early stages of chronic viral infections are thought to influence disease outcome. Using HIV as a model, we examined virus-specific cytotoxic T lymphocytes (CTLs), T helper cells, and viral genetic diversity in relation to duration of infection and subsequent response to antiviral therapy. Individuals with acute HIV-1 infection treated before seroconversion had weaker CTL responses directed at fewer epitopes than persons who were treated after seroconversion. However, treatment-induced control of viremia was associated with the development of strong T helper cell responses in both groups. After 1 yr of antiviral treatment initiated in acute or early infection, all epitope-specific CTL responses persisted despite undetectable viral loads. The breadth and magnitude of CTL responses remained significantly less in treated acute infection than in treated chronic infection, but viral diversity was also significantly less with immediate therapy. We conclude that early treatment of acute HIV infection leads to a more narrowly directed CTL response, stronger T helper cell responses, and a less diverse virus population. Given the need for T helper cells to maintain effective CTL responses and the ability of virus diversification to accommodate immune escape, we hypothesize that early therapy of primary infection may be beneficial despite induction of less robust CTL responses. These data also provide rationale for therapeutic immunization aimed at broadening CTL responses in treated primary HIV infection. PMID:11148221

  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 durin...... surgery and oral melatonin treatment for 3 days after surgery on biochemical markers of oxidative and inflammatory stress.......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...

  11. Blastogenic response of human lymphocytes to early antigen(s) of human cytomegalovirus.

    OpenAIRE

    Waner, J L; Kong, N; Biano, S

    1983-01-01

    The lymphocytes of asymptomatic, seropositive donors demonstrated blastogenic responses to early antigens of human cytomegalovirus whether or not antibodies to early antigens were detectable. The lymphocytes of six of nine patients with active cytomegalovirus infections gave stimulation indexes of greater than or equal to 2.00 with antigens of productively infected cells, whereas only two patients demonstrated comparable stimulation indexes with early antigens. Four patients with stimulation ...

  12. Blastogenic response of human lymphocytes to early antigen(s) of human cytomegalovirus.

    OpenAIRE

    Waner, J L; Kong, N; Biano, S

    1983-01-01

    The lymphocytes of asymptomatic, seropositive donors demonstrated blastogenic responses to early antigens of human cytomegalovirus whether or not antibodies to early antigens were detectable. The lymphocytes of six of nine patients with active cytomegalovirus infections gave stimulation indexes of greater than or equal to 2.00 with antigens of productively infected cells, whereas only two patients demonstrated comparable stimulation indexes with early antigens. Four patients with stimulation ...

  13. Measuring Early Childhood Teacher Candidates' Conceptualizations of a Culturally Responsive Classroom Ecology

    Science.gov (United States)

    Flores, Belinda Bustos; Riojas-Cortez, Mari

    2009-01-01

    With the increase of Latino preschoolers, it is pressing that early childhood teachers are prepared to create a high quality environment in which all children can succeed. Using the frameworks of cultural responsiveness and classroom management, we developed the Early Childhood Ecology Scale (ECES) as an observational and reflective tool to…

  14. Arterial stiffness and 24 h ambulatory blood pressure monitoring in young healthy volunteers: the early vascular ageing Aristotle University Thessaloniki Study (EVA-ARIS Study).

    Science.gov (United States)

    Kotsis, Vasilios; Stabouli, Stella; Karafillis, Ioannis; Papakatsika, Sofia; Rizos, Zoe; Miyakis, Spiros; Goulopoulou, Sofia; Parati, Gianfranco; Nilsson, Peter

    2011-11-01

    Differences in 24 h blood pressure (BP) monitoring parameters such as average 24 h BP, day to night BP ratio and BP variability could have an impact in arterial stiffness. The study hypothesis was that despite similar average BP values in ambulatory blood pressure monitoring subjects with increased 24 h BP variability may have increased arterial stiffness. The study population consisted of 115 consecutive young healthy volunteers. Carotid-femoral PWV was measured in all subjects. Clinic BP was measured and an appropriate cuff was fitted on the non-dominant arm of each subject for a 24 h ambulatory blood pressure monitoring session. Waist to hip ratio as well as BMI was measured. Family history and smoking habits were recorded. In univariate analysis, estimated carotid-femoral PWV showed a significant correlation with age, weight, waist circumference, height, clinic systolic and diastolic BP, 24-h systolic and diastolic BP, 24-h pulse pressure, 24-h systolic and diastolic BP variability, daytime systolic and diastolic BP, daytime pulse pressure, daytime systolic and diastolic BP variability, nighttime systolic BP, nighttime pulse pressure and nighttime systolic BP variability. In multivariate regression analysis, age (B=0.95, Parterial stiffness. In conclusions, increased 24 h systolic BP variability is associated with arterial stiffness in young healthy volunteers. Pulse wave velocity in a young healthy population is useful to identify determinants of premature arterial stiffness, thus further elucidating the aspects of early vascular ageing. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  15. Effect of intensive versus moderate lipid lowering on endothelial function and vascular responsiveness to angiotensin II in stable coronary artery disease.

    Science.gov (United States)

    van der Harst, Pim; Wagenaar, Lodewijk J; Buikema, Hendrik; Voors, Adriaan A; Plokker, H W Thijs; Morshuis, Wim J; Six, A Jacob; Boonstra, Piet W; Nickenig, Georg; Wassmann, Sven; van Veldhuisen, Dirk J; van Gilst, Wiek H

    2005-11-15

    Recent evidence has demonstrated that intensive lipid-lowering therapy with a high-dose statin provides significant clinical benefit beyond moderate lipid-lowering therapy. However, dose-dependent effects of short-term statin therapy on vascular function have not been demonstrated. We studied endothelial function and vascular responsiveness to angiotensin II in patients who had coronary artery diseased and were randomized to receive low- or high-dose atorvastatin (10 or 80 mg, respectively) or placebo. Internal thoracic artery segments were obtained during coronary bypass surgery and studied in vitro. Endothelium-dependent vasodilation was increased with atorvastatin therapy (p = 0.035) but was significantly increased further in patients who received 80 mg compared with those who received 10 mg of atorvastatin (p = 0.05). Endothelium improvement was accompanied by decreased vascular response to angiotensin II (p = 0.039). These findings suggest a mechanism for the clinical benefit of intensive lipid-lowering treatment in coronary heart disease.

  16. 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.

  17. Defining Clinical Response Criteria and Early Response Criteria for Precision Oncology: Current State-of-the-Art and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Vivek Subbiah

    2017-02-01

    Full Text Available In this era of precision oncology, there has been an exponential growth in the armamentarium of genomically targeted therapies and immunotherapies. Evaluating early responses to precision therapy is essential for “go” versus “no go” decisions for these molecularly targeted drugs and agents that arm the immune system. Many different response assessment criteria exist for use in solid tumors and lymphomas. We reviewed the literature using the Medline/PubMed database for keywords “response assessment” and various known response assessment criteria published up to 2016. In this article we review the commonly used response assessment criteria. We present a decision tree to facilitate selection of appropriate criteria. We also suggest methods for standardization of various response assessment criteria. The relevant response assessment criteria were further studied for rational of development, key features, proposed use and acceptance by various entities. We also discuss early response evaluation and provide specific case studies of early response to targeted therapy. With high-throughput, advanced computing programs and digital data-mining it is now possible to acquire vast amount of high quality imaging data opening up a new field of “omics in radiology”—radiomics that complements genomics for personalized medicine. Radiomics is rapidly evolving and is still in the research arena. This cutting-edge technology is poised to move soon to the mainstream clinical arena. Novel agents with new mechanisms of action require advanced molecular imaging as imaging biomarkers. There is an urgent need for development of standardized early response assessment criteria for evaluation of response to precision therapy.

  18. 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.

  19. Simultaneous occlusion of left anterior descending and left circumflex arteries by very late stent thrombosis: vascular response to drug-eluting stents assessed by intravascular ultrasound.

    Science.gov (United States)

    Yamawaki, Masahiro; Onuma, Yoshinobu; Nakano, Masatsugu; Muramatsu, Takashi; Nakatani, Shimpei; Ishibashi, Yuki; Ishimori, Hiroshi; Hirano, Keisuke; Ito, Yoshiaki; Tsukahara, Reiko; Muramatsu, Toshiya

    2015-11-01

    Very late stent thrombosis (VLST) is a catastrophic complication after implantation of a drug-eluting stent (DES). It has been reported that VLST is associated with pathological changes, which often include late acquired incomplete stent apposition (LAISA) with thrombus formation. In addition, the vascular response to the stent (evaginations, neointimal growth, and thrombosis) and the incidence of LAISA are reported to vary among the different types of DES. We experienced a patient with cardiogenic shock induced by simultaneous VLST of both the left anterior descending artery (LAD) and the left circumflex artery (LCX) at 3 years after implantation of two sirolimus-eluting stents. Intravascular ultrasound (IVUS) showed LAISA of both arteries. A paclitaxel-eluting stent, which had been implanted in the right coronary artery 3 years earlier, did not show such a finding. IVUS revealed "different vascular reactions" to "different types of DES" in this patient.

  20. Early nuclear alterations and immunohistochemical expression of Ki-67, Erb-B2, vascular endothelial growth factor (VEGF), transforming growth factor (TGF-beta1) and integrine-linked kinase (ILK) two days after tamoxifen in breast carcinoma.

    Science.gov (United States)

    Morena, A M L; Oshima, C T F; Gebrim, L H; Egami, M I; Silva, M R R; Segreto, R A; Giannotti Filho, O; Teixeira, V P C; Segreto, H R C

    2004-01-01

    The purpose of the present study was to evaluate breast carcinoma samples before and two days after treatment with tamoxifen in order to analyse early histopathological alterations--particularlynuclear alterations-- as well as immunohistochemical expression of Ki-67, Erb-B2, VEGF, TGF-beta1 and ILK proteins. Twenty one cases of invasive ductal and lobular breast carcinoma were studied. Patients were submitted to biopsy of the lesion and, after confirmation of the diagnosis, they received 20 mg of tamoxifen a day, beginning two days before surgery. The samples obtained during biopsy and after surgery were stained with HE for histopathological diagnosis. Estrogen receptor was positive in 18 cases and negative in 3. The immunohistochemical method was applied for the detection of Ki-67, Erb-B2, protein, vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF-beta1) and integrin linked kinase (ILK). Two days after tamoxifen treatment, the following results were observed: 1) decrease in the cell volume, chomatine condensation, nucleoli less evident and clearly defined nuclear limits; 2) significant reduction in the expression of Erb-B2 protein and significant increase in the expression of TGF-beta1 protein; 3) expression of others proteins (Ki-67, VEGF and ILK) was not altered during the indicated time frame. Our results suggest that analyzing nuclear alterations and expression of Erb-B2 and TGF-beta1 proteins would be useful to assess the initial response to tamoxifen.

  1. 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

    Voltage-gated calcium channels (Cav ) are important regulators of vascular tone and are attractive targets for pharmacological treatment of hypertension. The clinical used calcium blockers are often not selective for one channel but affect several types of calcium channels (Hansen 2015). L...

  2. Early Biventricular Molecular Responses to an Acute Myocardial Infarction

    OpenAIRE

    Erdal, Cenk; Karakülah, Gökhan; Fermancı, Emel; Kunter, İmge; Silistreli, Erdem; Tülay CANDA; Erdal, Esra; Hepaguslar, Hasan

    2011-01-01

    Background: Acute myocardial infarction (AMI) remains as one of the most common lethal diseases in the world and therefore it is necessary to understand its effect on molecular basis. Genome-wide microarray analysis provides us to predict potential biomarkers and signaling pathways for this purpose. Objectives: The aim of this study is to understand the molecular basis of the immediate right ventricular cellular response to left ventricular AMI. Material and Methods: A rat model of left anter...

  3. Vascular rings.

    Science.gov (United States)

    Backer, Carl L; Mongé, Michael C; Popescu, Andrada R; Eltayeb, Osama M; Rastatter, Jeffrey C; Rigsby, Cynthia K

    2016-06-01

    The term vascular ring refers to congenital vascular anomalies of the aortic arch system that compress the esophagus and trachea, causing symptoms related to those two structures. The most common vascular rings are double aortic arch and right aortic arch with left ligamentum. Pulmonary artery sling is rare and these patients need to be carefully evaluated for frequently associated tracheal stenosis. Another cause of tracheal compression occurring only in infants is the innominate artery compression syndrome. In the current era, the diagnosis of a vascular ring is best established by CT imaging that can accurately delineate the anatomy of the vascular ring and associated tracheal pathology. For patients with a right aortic arch there recently has been an increased recognition of a structure called a Kommerell diverticulum which may require resection and transfer of the left subclavian artery to the left carotid artery. A very rare vascular ring is the circumflex aorta that is now treated with the aortic uncrossing operation. Patients with vascular rings should all have an echocardiogram because of the incidence of associated congenital heart disease. We also recommend bronchoscopy to assess for additional tracheal pathology and provide an assessment of the degree of tracheomalacia and bronchomalacia. The outcomes of surgical intervention are excellent and most patients have complete resolution of symptoms over a period of time. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Subfoveal choroidal thickness as a predictor of treatment response to anti-vascular endothelial growth factor therapy for polypoidal choroidal vasculopathy.

    Science.gov (United States)

    Kim, Hyesun; Lee, Sung Chul; Kwon, Kye Yoon; Lee, Ji Hwan; Koh, Hyoung Jun; Byeon, Suk Ho; Kim, Sung Soo; Kim, Min; Lee, Christopher Seungkyu

    2016-08-01

    To investigate whether subfoveal choroidal thickness predicted treatment response to anti-vascular endothelial growth factor (VEGF) in polypoidal choroidal vasculopathy (PCV). This retrospective observational case series included 66 eyes of 60 patients who were diagnosed with new-onset PCV and who were followed for a minimum of 6 months. Patients received three monthly intravitreal injections of 0.5 mg ranibizumab or 1.25 mg bevacizumab, at baseline, month 1, and month 2. "Good responders" were defined as those who showed complete resolution of subretinal and/or intraretinal fluid at month 3 after the loading injections, whereas "poor responders" were defined as those who showed persistent retinal fluid on optical coherence tomography (OCT) at month 3 after treatment. Differences in best-corrected visual acuity, indocyanine green angiography, and spectral domain-OCT findings at baseline were analyzed between the two groups. The mean patient age was 68.2 ± 9.7 years, and the mean follow-up period was 27 ± 21 months. The mean subfoveal choroidal thickness was 273 ± 117 μm, and choroidal vascular hyperpermeability was observed in 35 eyes (53.0 %). Thirty-three eyes (50 %) showed good response to treatment, and a thinner subfoveal choroid at baseline significantly correlated with favorable treatment response (P = 0.024). However, there was no significant relationship between treatment response and choroidal vascular hyperpermeability (P = 0.999). The subfoveal choroid was found to be significantly thinner among patients who achieved complete resolution of macular exudation after three loading injections of anti-VEGF agents.

  5. Early response genes in the pathogenesis of cancer of the cervix uteri: a review

    Directory of Open Access Journals (Sweden)

    O. V. Kurmyshkina

    2011-01-01

    Full Text Available Early response genes are a group of proto-oncogenes that are the first to be activated in cell stimulation with different growth factors and to be involved in the regulation of cell proliferation and differentiation. Large amount of information supporting that altered expression of these genes is one of the central and earliest events of carcinogenesis has been accumulated. In this connection, it is promising to use early response genes as diagnostic and prognostic markers for the detection and combination therapy of cancer of the cervix uteri, one of the most common gynecological malignancies characterized by high mortality rates and difficulties in early diagnosis. The theoretical basis for these promises is the found mechanisms for the interaction of early response genes with human papillomavirus genome, the main cause of cervix uteri cancer.

  6. 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...

  7. Storey building early monitoring based on rapid seismic response analysis

    Science.gov (United States)

    Julius, Musa, Admiral; Sunardi, Bambang; Rudyanto, Ariska

    2016-05-01

    Within the last decade, advances in the acquisition, processing and transmission of data from seismic monitoring has contributed to the growth in the number structures instrumented with such systems. An equally important factor for such growth can be attributed to the demands by stakeholders to find rapid answers to important questions related to the functionality or state of "health" of structures during and immediately of a seismic events. Consequently, this study aims to monitor the storey building based on seismic response i. e. earthquake and tremor analysis at short time lapse using accelerographs data. This study used one of storey building (X) in Jakarta city that suffered the effects of Kebumen earthquake January 25th 2014, Pandeglang earthquake July 9th 2014, and Lebak earthquake November 8th 2014. Tremors used in this study are tremors after the three following earthquakes. Data processing used to determine peak ground acceleration (PGA), peak ground velocity (PGV), peak ground displacement (PGD), spectral acceleration (SA), spectral velocity (SV), spectral displacement (SD), A/V ratio, acceleration amplification and effective duration (te). Then determine the natural frequency (f0) and peak of H/V ratio using H/V ratio method.The earthquakes data processing result shows the value of peak ground motion, spectrum response, A/V ratio and acceleration amplification increases with height, while the value of the effective duration give a different viewpoint of building dynamic because duration of Kebumen earthquake shows the highest energy in the highest floor but Pandeglang and Lebak earthquake in the lowest floor. Then, tremors data processing result one month after each earthquakes shows the natural frequency of building in constant value. Increasing of peak ground motion, spectrum response, A/V ratio, acceleration amplification, then decrease of effective duration following the increase of building floors shows that the building construction supports the

  8. VASCULAR SURGERY

    African Journals Online (AJOL)

    Thromboses can result from venous stasis, vascular injury or hypercoagulability, and those involving the deep veins proximal to the knee are linked to an increased risk of PE.2 .... tool for DVT in hospitalised patients, where higher scores.

  9. Vascular Dementia

    Science.gov (United States)

    ... that includes enjoyable activities well within the comfort zone of the person with vascular dementia. New situations, ... your cholesterol in check. A healthy, low-fat diet and cholesterol-lowering medications if you need them ...

  10. Predictors of Responsiveness to Early Literacy Intervention: A 10-Year Update

    Science.gov (United States)

    Lam, Elizabeth A.; McMaster, Kristen L.

    2014-01-01

    The purpose of this review was to update previous reviews on factors related to students' responsiveness to early literacy intervention. The 14 studies in this synthesis used experimental designs, provided small-group or one-on-one reading interventions, and analyzed factors related to responsiveness to those interventions. Participants were…

  11. 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…

  12. Evidence-Based Early Reading Practices within a Response to Intervention System

    Science.gov (United States)

    Bursuck, Bill; Blanks, Brooke

    2010-01-01

    Many students who experience reading failure are inappropriately placed in special education. A promising response to reducing reading failure and the overidentification of students for special education is Response to Intervention (RTI), a comprehensive early detection and prevention system that allows teachers to identify and support struggling…

  13. Preterm Children at Early Adolescence and Continuity and Discontinuity in Maternal Responsiveness from Infancy.

    Science.gov (United States)

    Beckwith, Leila; And Others

    1992-01-01

    Children whose mothers were consistently more responsive during the children's infancy and early adolescence achieved higher IQ and arithmetic scores, had more positive self-esteem, and were reported by teachers to exhibit fewer behavior problems than children of mothers who were consistently less responsive. (BC)

  14. 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…

  15. vascular hemiplegia

    OpenAIRE

    Voto Bernales, Jorge; Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú

    2014-01-01

    The vascular hemiplegia is the functional disorder of a lateral half of the body produced by alterations of cerebral vessels. Should review the concepts of this common condition, with the dual aim of expanding its nosographic value and considering the hemiplegic patient as worthy of the highest professional care La hemiplejia vascular, es el trastorno funcional de una mitad lateral del cuerpo producido por alteraciones de los vasos cerebrales. Conviene revisar los conceptos sobre esta frec...

  16. vascular hemiplegia

    OpenAIRE

    Voto Bernales, Jorge; Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú

    2014-01-01

    The vascular hemiplegia is the functional disorder of a lateral half of the body produced by alterations of cerebral vessels. Should review the concepts of this common condition, with the dual aim of expanding its nosographic value and considering the hemiplegic patient as worthy of the highest professional care La hemiplejia vascular, es el trastorno funcional de una mitad lateral del cuerpo producido por alteraciones de los vasos cerebrales. Conviene revisar los conceptos sobre esta frec...

  17. Prediction and set-dependent scaling of early postural responses in cerebellar patients.

    Science.gov (United States)

    Timmann, D; Horak, F B

    1997-02-01

    We reported previously that patients with cerebellar deficits were unable to scale the magnitude of their early automatic postural responses to the predicted amplitudes of surface translations based on central set from prior experience. The present study investigated whether this deficit in set-dependent amplitude scaling was based predominantly on the cerebellar patient's disability (i) to predict perturbation amplitudes on the basis of prior experience, (ii) to scale the gain or magnitude of upcoming postural responses or (iii) to habituate postural responses. The increase in size of the early postural response when a larger than actual platform amplitude was expected and decrease when a smaller one was expected was defined as a measure of set-dependent amplitude prediction. The suppression of the postural response when the same platform velocity was repeated was used as a measure of habituation. The correlation between the size of early postural responses and platform amplitudes when presented serially, but not randomly, tested the ability to scale the gain of postural responses based on prior experience. Results show that although cerebellar patients could predict perturbation amplitudes based on prior experience, they could not use this prediction to modify precisely the gain of responses. The ability to habituate the magnitude of postural responses was not affected by cerebellar lesions. Thus, the cerebellum might not be critical for predicting upcoming events or for habituating to repeated postural stimuli, although it is important for accurate tuning of response gain based on prediction.

  18. The interrelations between malfunctioning DNA damage response (DDR) and the functionality of the neuro-glio-vascular unit.

    Science.gov (United States)

    Barzilai, Ari

    2013-08-01

    A hallmark of neurodegenerative diseases is impairment of certain aspects of "brain functionality". Brain functionality is defined as the total input and output of the brain's neural circuits and networks. A given brain degenerative disorder does not deregulate total brain functionality but rather the activity of specific circuits in a given network, affecting their organization and topology, their cell numbers, their cellular functionality, and the interactions between neural circuits. Similarly, our concept of neurodegenerative diseases, which for many years revolved around neural survival or death, has now been extended to emphasize the role of glia. In particular, the role of glial cells in neuro-vascular communication is now known to be central to the effect of insults to the nervous system. In addition, a malfunctioning vascular system likely plays a role in the etiology of certain neurodegenerative diseases. Thus, the symptoms of neurodegenerative or more correctly brain degenerative disease are, to a very large extent, a result of impairment in glial cells that lead to pathological neuro-vascular interactions that, in turn, generate a rather "hostile" environment in which the neurons fail to function. These events lead to systematic neural cell death on a scale that appears to be proportional to the severity of the neurological deficit.

  19. Mir1-CP, a novel defense cysteine protease accumulates in maize vascular tissues in response to herbivory.

    Science.gov (United States)

    Lopez, Lorena; Camas, Alberto; Shivaji, Renuka; Ankala, Arunkanth; Williams, Paul; Luthe, Dawn

    2007-07-01

    When lepidopteran larvae feed on the insect-resistant maize genotype Mp708 there is a rapid accumulation of a defensive cysteine protease, Maize insect resistance 1-cysteine protease (Mir1-CP), at the feeding site. Silver-enhanced immunolocalization visualized with both light and transmission electron microscopy was used to determine the location of Mir1-CP in the maize leaf. The results indicated that Mir1-CP is localized predominantly in the phloem of minor and intermediate veins. After 24 h of larval feeding, Mir1-CP increased in abundance in the vascular parenchyma cells and in the thick-walled sieve element (TSE); it was also found localized to the bundle sheath and mesophyll cells. In situ hybridization of mRNA encoding Mir1-CP indicated that the primary sites of Mir1-CP synthesis in the whorl are the vascular parenchyma and bundle sheath cells. In addition to the phloem, Mir1-CP was also found in the metaxylem of the leaf and root. After 24 h of foliar feeding, the amount of Mir1-CP in the root xylem increased and it appeared to move from xylem parenchyma into the root metaxylem elements. The accumulation of Mir1-CP in maize vascular elements suggests Mir1-CP may move through these tissues to defend against insect herbivores.

  20. Ageing and vascular ageing

    Science.gov (United States)

    Jani, B; Rajkumar, C

    2006-01-01

    There is an age related decline in various physiological processes. Vascular ageing is associated with changes in the mechanical and the structural properties of the vascular wall, which leads to the loss of arterial elasticity and reduced arterial compliance. Arterial compliance can be measured by different parameters like pulse wave velocity, augmentation index, and systemic arterial compliance. There is evidence that arterial compliance is reduced in disease states such as hypertension, diabetes, and end stage renal failure. Changes in arterial compliance can be present before the clinical manifestation of cardiovascular disease. Pharmacological and non‐pharmacological measures have been shown to improve arterial compliance. Arterial compliance may constitute an early cardiovascular risk marker and may be useful in assessing the effects of drugs on the cardiovascular system. Pharmacogenetics and genetics of arterial compliance in the future will improve our knowledge and understanding about vascular ageing. PMID:16754702

  1. 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.

  2. Two Decades of Progress in Vascular Medicine

    OpenAIRE

    Leeper, Nicholas J.; Lee, Jason T.; Cooke, John P.

    2011-01-01

    Twenty years has passed since our first call for a new specialty in Vascular Medicine(1). This proposal was motivated by novel insights into vascular disease, advances in diagnostics and therapies directed toward the vasculature, and a growing population of patients with vascular disease. Now, with two decades of perspective, we reaffirm the call for Vascular Medicine, highlight the field’s early successes, and provide our vision for the future of the specialty.

  3. Relationships between the extent of apnea-induced bradycardia and the vascular response in the arm and leg during dynamic two-legged knee extension exercise.

    Science.gov (United States)

    Nishiyasu, Takeshi; Tsukamoto, Rina; Kawai, Katsuhito; Hayashi, Keiji; Koga, Shunsaku; Ichinose, Masashi

    2012-02-01

    Our aim was to test the hypothesis that apnea-induced hemodynamic responses during dynamic exercise in humans differ between those who show strong bradycardia and those who show only mild bradycardia. After apnea-induced changes in heart rate (HR) were evaluated during dynamic exercise, 23 healthy subjects were selected and divided into a large response group (L group; n = 11) and a small response group (S group; n = 12). While subjects performed a two-legged dynamic knee extension exercise at a work load that increased HR by 30 beats/min, apnea-induced changes in HR, cardiac output (CO), mean arterial pressure (MAP), arterial O(2) saturation (Sa(O(2))), forearm blood flow (FBF), and leg blood flow (LBF) were measured. During apnea, HR in the L group (54 ± 2 beats/min) was lower than in the S group (92 ± 3 beats/min, P leg vascular conductance (LVC), and total vascular conductance (TVC) were all reduced, and MAP was increased in both groups, although the changes in CO, TVC, LBF, LVC, and MAP were larger in the L group than in the S group (P muscle regions.

  4. Hippocampal expression of synaptic structural proteins and phosphorylated cAMP response element-binding protein in a rat model of vascular dementia induced by chronic cerebral hypoperfusion

    Institute of Scientific and Technical Information of China (English)

    Hui Zhao; Zhiyong Li; Yali Wang; Qiuxia Zhang

    2012-01-01

    The present study established a rat model of vascular dementia induced by chronic cerebral hy-poperfusion through permanent ligation of bilateral common carotid arteries. At 60 days after mod-eling, escape latency and swimming path length during hidden-platform acquisition training in Morris water maze significantly increased in the model group. In addition, the number of accurate crossings over the original platform significantly decreased, hippocampal CA1 synaptophysin and growth-associated protein 43 expression significantly decreased, cAMP response element-binding protein expression remained unchanged, and phosphorylated cAMP response element-binding protein expression significantly decreased. Results suggested that abnormal expression of hippo-campal synaptic structural protein and cAMP response element-binding protein phosphorylation played a role in cognitive impairment following chronic cerebral hypoperfusion.

  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...... the vastus lateralis. The main findings were that RFD in the late phase of rising muscle force increased in response to resistance training whereas early RFD remained unchanged and early relative RFD (i.e., RFD/MVC) decreased. Quantitatively, muscle fiber cross-sectional area and MVC increased whereas......-intensity resistance training due to differential influences of qualitative and quantitative muscular adaptations on early and later phases of rising muscle force....

  6. Feeding mice with Aloe vera gel diminishes L-1 sarcoma-induced early neovascular response and tumor growth.

    Science.gov (United States)

    Kocik, Janusz; Bałan, Barbara Joanna; Zdanowski, Robert; Jung, Leszek; Skopińska-Różewska, Ewa; Skopiński, Piotr

    2014-01-01

    Aloe vera (Aloe arborescens, aloe barbadensis) is a medicinal plant belonging to the Liliaceae family. Aloe vera gel prepared from the inner part of Aloe leaves is increasingly consumed as a beverage dietary supplement. Some data suggest its tumor growth modulatory properties. The aim of the present study was to evaluate in Balb/c mice the in vivo influence of orally administered Aloe vera drinking gel on the syngeneic L-1 sarcoma tumor growth and its vascularization: early cutaneous neovascular response, tumor-induced angiogenesis (TIA test read after 3 days), and tumor hemoglobin content measured 14 days after L-1 sarcoma cell grafting. Feeding mice for 3 days after tumor cell grafting with 150 μl daily dose of Aloe vera gel significantly diminished the number of newly-formed blood vessels in comparison to the controls. The difference between the groups of control and Aloe-fed mice (150 μl daily dose for 14 days) with respect to the 14 days' tumor volume was on the border of statistical significance. No difference was observed in tumor hemoglobin content.

  7. Downregulation of an astrocyte-derived inflammatory protein, S100B, reduces vascular inflammatory responses in brains persistently infected with Borna disease virus.

    Science.gov (United States)

    Ohtaki, Naohiro; Kamitani, Wataru; Watanabe, Yohei; Hayashi, Yohei; Yanai, Hideyuki; Ikuta, Kazuyoshi; Tomonaga, Keizo

    2007-06-01

    Borna disease virus (BDV) is a neurotropic virus that causes a persistent infection in the central nervous system (CNS) of many vertebrate species. Although a severe reactive gliosis is observed in experimentally BDV-infected rat brains, little is known about the glial reactions contributing to the viral persistence and immune modulation in the CNS. In this regard, we examined the expression of an astrocyte-derived factor, S100B, in the brains of Lewis rats persistently infected with BDV. S100B is a Ca(2+)-binding protein produced mainly by astrocytes. A prominent role of this protein appears to be the promotion of vascular inflammatory responses through interaction with the receptor for advanced glycation end products (RAGE). Here we show that the expression of S100B is significantly reduced in BDV-infected brains despite severe astrocytosis with increased glial fibrillary acidic protein immunoreactivity. Interestingly, no upregulation of the expression of S100B, or RAGE, was observed in the persistently infected brains even when incited with several inflammatory stimuli, including lipopolysaccharide. In addition, expression of the vascular cell adhesion molecule 1 (VCAM-1), as well as the infiltration of encephalitogenic T cells, was significantly reduced in persistently infected brains in which an experimental autoimmune encephalomyelitis was induced by immunization with myelin-basic protein. Furthermore, we demonstrated that the continuous activation of S100B in the brain may be necessary for the progression of vascular immune responses in neonatally infected rat brains. Our results suggested that BDV infection may impair astrocyte functions via a downregulation of S100B expression, leading to the maintenance of a persistent infection.

  8. Effects of carnitine supplementation on flow-mediated dilation and vascular inflammatory responses to a high-fat meal in healthy young adults.

    Science.gov (United States)

    Volek, Jeff S; Judelson, Daniel A; Silvestre, Ricardo; Yamamoto, Linda M; Spiering, Barry A; Hatfield, Disa L; Vingren, Jakob L; Quann, Erin E; Anderson, Jeffrey M; Maresh, Carl M; Kraemer, William J

    2008-11-15

    Because carnitine has been shown to decrease oxidative stress and improve endothelial cell functioning, we examined the effects of carnitine supplementation on postprandial flow-mediated dilation (FMD) and circulating biomarkers of inflammation and oxidative stress after a high-fat meal. A randomized, double-blind, placebo-controlled, crossover study design was used. Thirty men and women (age 30 +/- 8 year, body mass 72.9 +/- 17.1 kg, body fat 13.0 +/- 6.4%) participated in 2 vascular testing days, each preceded by 3 weeks of supplementation with either 2 g/day of L-Carnitine (L-Carnitine L-Tartrate) or placebo with a 3- to 5-week washout period between trials. Brachial artery FMD in response to 5 minutes of upper arm occlusion and circulating markers of oxidative stress and inflammation were measured in the fasting state and after a standardized high-fat meal. After 3 weeks of supplementation, peak FMD in the fasting state was similar between the carnitine and placebo trials, averaging 6.6%. Peak FMD during the postprandial period decreased to 5.8% at 1.5 hours during placebo and increased to 7.7% during the carnitine trial (n = 30: p = 0.043 for supplement by time interaction effect). This improvement in postprandial vascular function was most dramatic in subjects who showed a decrease in peak FMD in response to the meal (n = 15: p = 0.003 for supplement by time interaction effect). There was a significant increase in postprandial lipemia and plasma interleukin-6 but no effect of supplementation. There were no significant postprandial changes or supplement effects for plasma tumor necrosis factor-alpha and malondialdehyde. In conclusion, consistent with other work showing a beneficial effect of carnitine on vascular function, these findings indicate that carnitine supplementation in healthy individuals improves postprandial FMD after a high-fat meal.

  9. 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

    2012-08-01

    The effects of caffeine are mediated through its non-selective antagonistic effects on adenosine A(1) and A(2A) 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

  10. Early and late rate of force development: differential adaptive responses to resistance training?

    Science.gov (United States)

    Andersen, L L; Andersen, J L; Zebis, M K; Aagaard, P

    2010-02-01

    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 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 the vastus lateralis. The main findings were that RFD in the late phase of rising muscle force increased in response to resistance training whereas early RFD remained unchanged and early relative RFD (i.e., RFD/MVC) decreased. Quantitatively, muscle fiber cross-sectional area and MVC increased whereas, qualitatively, the relative proportion of type IIX muscle fibers decreased. Multiple regression analysis showed that while increased MVC positively influenced both early and late RFD, decreased-type IIX negatively influenced early RFD only. In conclusion, early and late RFD responded differently to high-intensity resistance training due to differential influences of qualitative and quantitative muscular adaptations on early and later phases of rising muscle force.

  11. Cost effectiveness of responsive stimulation and nutrition interventions on early child development outcomes in Pakistan.

    Science.gov (United States)

    Gowani, Saima; Yousafzai, Aisha K; Armstrong, Robert; Bhutta, Zulfiqar A

    2014-01-01

    Early childhood programs are heralded as a way to improve children's health and educational outcomes. However, few studies in developing countries calculate the effectiveness of quality early childhood interventions. Even fewer estimate the associated costs of such interventions. The study here looks at the costs and effectiveness of a cluster-randomized effectiveness trial on children from birth to 24 months in rural Sindh, Pakistan. Responsive stimulation and/or enhanced nutrition interventions were integrated in the Lady Health Worker program in Pakistan. Outcomes suggest that children who receive responsive stimulation had significantly better development outcomes at 24 months than those who only received enhanced nutrition intervention. A cost-effectiveness analysis of the results verifies that early childhood interventions that include responsive stimulation are more cost effective than a nutrition intervention alone in promoting children's early development. Costs of a responsive stimulation intervention integrated in an existing community-based service providing basic health and nutrition care is approximately US$4 per month per child. We discuss these findings and make recommendations about scaling up and costs for future early child development programs. © 2014 New York Academy of Sciences.

  12. Early

    Directory of Open Access Journals (Sweden)

    Kamel Abd Elaziz Mohamed

    2014-04-01

    Conclusion: Early PDT is recommended for patients who require prolonged tracheal intubation in the ICU as outcomes like the duration of mechanical ventilation length of ICU stay and hospital stay were significantly shorter in early tracheostomy.

  13. EARLY RESPONSIVE to DEHYDRATION 15, a new transcription factor that integrates stress signaling pathways.

    Science.gov (United States)

    Alves, Murilo S; Fontes, Elizabeth P B; Fietto, Luciano G

    2011-12-01

    The Early Responsive to Dehydration (ERD) genes are defined as those genes that are rapidly activated during drought stress. The encoded proteins show a great structural and functional diversity, with a particular class of proteins acting as connectors of stress response pathways. Recent studies have shown that ERD15 proteins from different species of plants operate in cross-talk among different response pathways. In this mini-review, we show the recent progress on the functional role of this diverse family of proteins and demonstrate that a soybean ERD15 homolog can act as a connector in stress response pathways that trigger a programmed cell death signal.

  14. Transcriptional dynamics reveal critical roles for non-coding RNAs in the immediate-early response.

    Directory of Open Access Journals (Sweden)

    Stuart Aitken

    2015-04-01

    Full Text Available The immediate-early response mediates cell fate in response to a variety of extracellular stimuli and is dysregulated in many cancers. However, the specificity of the response across stimuli and cell types, and the roles of non-coding RNAs are not well understood. Using a large collection of densely-sampled time series expression data we have examined the induction of the immediate-early response in unparalleled detail, across cell types and stimuli. We exploit cap analysis of gene expression (CAGE time series datasets to directly measure promoter activities over time. Using a novel analysis method for time series data we identify transcripts with expression patterns that closely resemble the dynamics of known immediate-early genes (IEGs and this enables a comprehensive comparative study of these genes and their chromatin state. Surprisingly, these data suggest that the earliest transcriptional responses often involve promoters generating non-coding RNAs, many of which are produced in advance of canonical protein-coding IEGs. IEGs are known to be capable of induction without de novo protein synthesis. Consistent with this, we find that the response of both protein-coding and non-coding RNA IEGs can be explained by their transcriptionally poised, permissive chromatin state prior to stimulation. We also explore the function of non-coding RNAs in the attenuation of the immediate early response in a small RNA sequencing dataset matched to the CAGE data: We identify a novel set of microRNAs responsible for the attenuation of the IEG response in an estrogen receptor positive cancer cell line. Our computational statistical method is well suited to meta-analyses as there is no requirement for transcripts to pass thresholds for significant differential expression between time points, and it is agnostic to the number of time points per dataset.

  15. Sevoflurane effects on cyclic adenosine monophosphate response element binding protein, phosphorylated cyclic adenosine monophosphate response element binding protein, and Livin expression in the cortex and hippocampus of a vascular cognitive impairment rat model

    Institute of Scientific and Technical Information of China (English)

    Bin Wu; Ling Dan; Xianlin Zhu

    2009-01-01

    BACKGROUND: Neuronal necrosis and apoptosis play important roles in the pathophysiology of cerebral ischemia and resulting cognitive impairment. However, inhibition of neuronal necrosis and apoptosis has been shown to attenuate cognitive impairment following cerebral ischemia.OBJECTIVE: To investigate the effects of sevoflurane on cyclic adenosine monophosphate response element binding protein (CREB), phosphorylated CREB (pCREB), and Livin expression in the cortex and hippocampus of a rat model of vascular cognitive impairment.DESIGN, TIME AND SETTING: A randomized, controlled experiment was performed in the Chongqing Key Laboratory of Neurology between June 2007 and July 2008.MATERIALS: Sevoflurane was provided by Abbott Laboratory, UK; Morris water maze was provided by Chinese Academy of Medical Sciences, China; goat anti-rat CREB, goat anti-rat pCREB and goat anti-rat Livin antibodies were provided by Biosource International, USA.METHODS: A total of 42 female, Wistar rats were randomly assigned to the following groups: sham operation, vascular cognitive impairment, and sevoflurane treatment. The vascular cognitive impairment rat model was established by permanent bilateral occlusion of both common carotid arteries, and 1.0 MAC sevoflurane was immediately administered by inhalation for 2 hours.MAIN OUTCOME MEASURES: CREB, pCREB, and Livin expression was measured in the cortex and hippocampus by Western blot and reverse transcription-polymerase chain reaction. Behavior was evaluated with Morris water maze.RESULTS: CREB, pCREB, and Livin expression in the sevoflurane treatment group was significantly greater than the vascular cognitive impairment group (P<0.01). However, expression of CREB and pCREB was significantly less in the sevoflurane treatment and vascular cognitive impairment groups, compared with the sham operation group (P<0.01). Livin expression in the sevoflurane treatment and vascular cognitive impairment groups was significantly greater than the sham

  16. 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

  17. Vascular emergencies.

    Science.gov (United States)

    Semashko, D C

    1997-01-01

    This article reviews the initial assessment and emergent management of several common as well as uncommon vascular emergencies. Aortic dissection, aneurysms, and arterial occlusive disease are familiar but challenging clinical entities. Less frequently encountered conditions are also discussed including an aortic enteric fistula, mesenteric venous thrombosis, phlegmasia alba dolens, and subclavian vein thrombosis.

  18. Vascular Disease Foundation

    Science.gov (United States)

    ... Contact Us Vascular Disease What is Vascular Disease? Education and Awareness Vascular Diseases Abdominal Aortic Aneurysm Aortic Dissection Arteriovenous Malformation Atherosclerosis Buerger's Disease Carotid Artery Disease ...

  19. What Is Vascular Disease?

    Science.gov (United States)

    ... Contact Us Vascular Disease What is Vascular Disease? Education and Awareness Vascular Diseases Abdominal Aortic Aneurysm Aortic Dissection Arteriovenous Malformation Atherosclerosis Buerger's Disease Carotid Artery Disease ...

  20. Evidence for an Early Origin of Vernalization Responsiveness in Temperate Pooideae Grasses1[OPEN

    Science.gov (United States)

    McKeown, Meghan; Fjellheim, Siri

    2016-01-01

    The ability of plants to match their reproductive output with favorable environmental conditions has major consequences both for lifetime fitness and geographic patterns of diversity. In temperate ecosystems, some plant species have evolved the ability to use winter nonfreezing cold (vernalization) as a cue to ready them for spring flowering. However, it is unknown how important the evolution of vernalization responsiveness has been for the colonization and subsequent diversification of taxa within the northern and southern temperate zones. Grasses of subfamily Pooideae, including several important crops, such as wheat (Triticum aestivum), barley (Hordeum vulgare), and oats (Avena sativa), predominate in the northern temperate zone, and it is hypothesized that their radiation was facilitated by the early evolution of vernalization responsiveness. Predictions of this early origin hypothesis are that a response to vernalization is widespread within the subfamily and that the genetic basis of this trait is conserved. To test these predictions, we determined and reconstructed vernalization responsiveness across Pooideae and compared expression of wheat vernalization gene orthologs VERNALIZATION1 (VRN1) and VRN3 in phylogenetically representative taxa under cold and control conditions. Our results demonstrate that vernalization responsive Pooideae species are widespread, suggesting that this trait evolved early in the lineage and that at least part of the vernalization gene network is conserved throughout the subfamily. These results are consistent with the hypothesis that the evolution of vernalization responsiveness was important for the initial transition of Pooideae out of the tropics and into the temperate zone. PMID:27474116

  1. Evidence for an Early Origin of Vernalization Responsiveness in Temperate Pooideae Grasses.

    Science.gov (United States)

    McKeown, Meghan; Schubert, Marian; Marcussen, Thomas; Fjellheim, Siri; Preston, Jill C

    2016-09-01

    The ability of plants to match their reproductive output with favorable environmental conditions has major consequences both for lifetime fitness and geographic patterns of diversity. In temperate ecosystems, some plant species have evolved the ability to use winter nonfreezing cold (vernalization) as a cue to ready them for spring flowering. However, it is unknown how important the evolution of vernalization responsiveness has been for the colonization and subsequent diversification of taxa within the northern and southern temperate zones. Grasses of subfamily Pooideae, including several important crops, such as wheat (Triticum aestivum), barley (Hordeum vulgare), and oats (Avena sativa), predominate in the northern temperate zone, and it is hypothesized that their radiation was facilitated by the early evolution of vernalization responsiveness. Predictions of this early origin hypothesis are that a response to vernalization is widespread within the subfamily and that the genetic basis of this trait is conserved. To test these predictions, we determined and reconstructed vernalization responsiveness across Pooideae and compared expression of wheat vernalization gene orthologs VERNALIZATION1 (VRN1) and VRN3 in phylogenetically representative taxa under cold and control conditions. Our results demonstrate that vernalization responsive Pooideae species are widespread, suggesting that this trait evolved early in the lineage and that at least part of the vernalization gene network is conserved throughout the subfamily. These results are consistent with the hypothesis that the evolution of vernalization responsiveness was important for the initial transition of Pooideae out of the tropics and into the temperate zone.

  2. STIM1/Orai1 contributes to sex differences in vascular responses to calcium in spontaneously hypertensive rats.

    Science.gov (United States)

    Giachini, Fernanda R C; Lima, Victor V; Filgueira, Fernando P; Dorrance, Anne M; Carvalho, Maria Helena C; Fortes, Zuleica B; Webb, R Clinton; Tostes, Rita C

    2012-03-01

    Sex differences in Ca2+-dependent signalling and homoeostasis in the vasculature of hypertensive rats are well characterized. However, sex-related differences in SOCE (store-operated Ca2+ entry) have been minimally investigated. We hypothesized that vascular protection in females, compared with males, reflects decreased Ca2+ mobilization due to diminished activation of Orai1/STIM1 (stromal interaction molecule 1). In addition, we investigated whether ovariectomy in females affects the activation of the Orai1/STIM1 pathway. Endothelium-denuded aortic rings from male and female SHRSP (stroke-prone spontaneously hypertensive rats) and WKY (Wistar-Kyoto) rats and from OVX (ovariectomized) or sham female SHRSP and WKY rats were used to functionally evaluate Ca2+ influx-induced contractions. Compared with females, aorta from male SHRSP displayed: (i) increased contraction during the Ca2+-loading period; (ii) similar transient contraction during Ca2+ release from the intracellular stores; (iii) increased activation of STIM1 and Orai1, as shown by the blockade of STIM1 and Orai1 with neutralizing antibodies, which reversed the sex differences in contraction during the Ca2+-loading period; and (iv) increased expression of STIM1 and Orai1. Additionally, we found that aortas from OVX-SHRSP showed increased contraction during the Ca2+-loading period and increased Orai1 expression, but no changes in the SR (sarcoplasmic reticulum)-buffering capacity or STIM1 expression. These findings suggest that augmented activation of STIM1/Orai1 in aortas from male SHRSP represents a mechanism that contributes to sex-related impaired control of intracellular Ca2+ levels. Furthermore, female sex hormones may negatively modulate the STIM/Orai1 pathway, contributing to vascular protection observed in female rats.

  3. The bradykinin B2 receptor in the early immune response against Listeria infection

    NARCIS (Netherlands)

    Kaman, W.E.; Wolterink, A.F.W.M.; Bader, M.; Boele, L.C.L.; Kleij, D. van der

    2009-01-01

    The endogenous danger signal bradykinin was recently found implicated in the development of immunity against parasites via dendritic cells. We here report an essential role of the B2 (B2R) bradykinin receptor in the early immune response against Listeria infection. Mice deficient in B2R (B2R-/- mice

  4. 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…

  5. Pre-Service Teacher Disposition Development: Cultural Reciprocity and Responsivity in Early Childhood Special Education Practica

    Science.gov (United States)

    Van Steenberg, Vicki

    2012-01-01

    This qualitative Case Study explored the integrative process of pre-service teachers' disposition development for cultural reciprocity and responsiveness. Over the course of ten months, pre-service teachers completed two Early Childhood Special Education practica in diverse urban communities. The pre-service teachers were placed in public…

  6. 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.

    2006-01-01

    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…

  7. 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…

  8. MITOGENIC SIGNALS CONTROL TRANSLATION OF THE EARLY GROWTH-RESPONSE GENE-1 IN MYOGENIC CELLS

    NARCIS (Netherlands)

    MAASS, A; GROHE, C; OBERDORF, S; SUKHATME, VP; VETTER, H; NEYSES, L

    1994-01-01

    Muscle is a major site of expression of the early growth reponse gene-1 (Egr-1). To investigate its role in muscle proliferation and/or differentiation we studied the effect of a variety of growth factors on cultured mouse muscle So18 cells. Three groups of responses could be distinguished: 1. AII,

  9. The Confluence of Adverse Early Experience and Puberty on the Cortisol Awakening Response

    Science.gov (United States)

    Quevedo, Karina; Johnson, Anna E.; Loman, Michelle L.; LaFavor, Theresa L.; Gunnar, Megan

    2012-01-01

    Associations between early deprivation/neglect in the form of institutional care with the cortisol awakening response (CAR) were examined as a function of pubertal status among 12- and 13-year-old postinstitutionalized youth. CARs indexed hypothalamic-pituitary-adrenocortical reactivity. Postinstitutionalized youth were compared to youth adopted…

  10. 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 heat-inact

  11. Value of sympathetic skin response test in the early diagnosis of diabetic neuropathy

    Institute of Scientific and Technical Information of China (English)

    黄一宁; 贾志荣; 石昕; 孙相如

    2004-01-01

    Background Diabetic neuropathy is common in diabetes mellitus. The early stage of diabetic neuropathy is often symptomless and difficult to be treated. The aim of this study was to assess the correlation between the results of the sympathetic skin response (SSR) test and the development of diabetic neuropathy, and explore the use of SSR as an objective basis for the early diagnosis of diabetic neuropathy.Methods The latencies and amplitudes of initiation and of the N and P waves were determined by SSR testing of the extremities of 80 diabetic patients and 30 healthy controls. Results The latencies of initiation and of the N and P waves were significantly (P0.05). All but two patients (97.5%) demonstrated abnormal SSR in at least one limb. Conclusions SSR can detect early dysfunction of the small sympathetic fibers in people affected by diabetes mellitus, and may be a useful electrophysiological test for the early diagnosis of diabetic neuropathy.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. Hyperemic responses of the optic nerve head blood flow to chromatic equiluminant flicker are reduced by ocular hypertension and early glaucoma

    Science.gov (United States)

    Falsini, Benedetto; Riva, Charles E.; Salgarello, Tommaso; Logean, Eric; Colotto, Alberto; Giudiceandrea, Andrea

    2014-06-01

    We evaluated in ocular hypertension (OHT) and early glaucoma (EOAG) patients the optic nerve head (ONH) blood flow response (RF) to chromatic equiluminant flicker. This stimulus generates neural activity dominated by the parvo-cellular system. Eleven EOAG, 20 OHT patients, and 8 age-matched control subjects were examined. The blood flow (F) at the neuroretinal rim was continuously monitored by laser Doppler flowmetry before, during, and after a 60-s exposure to a 4 Hz, red-green equiluminant flicker stimulus (30 deg field). RF was expressed as percentage F-change during the last 20 s of flicker relative to baseline F. Responses were collected at a number of temporal sites. The highest RF value was used for subsequent analysis. As compared to controls, both OHT and EOAG patients showed a decrease (pRF. We conclude that RF elicited by chromatic equiluminant flicker is abnormally reduced in OHT and EOAG patients indicating an impairment of the parvo-cellular-mediated vasoactivity. This decrease of vascular response may occur independently of neural activity loss early in the disease process.

  17. 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.

  18. 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

  19. Pravastatin inhibits fibrinogen- and FDP-induced inflammatory response via reducing the production of IL-6, TNF-α and iNOS in vascular smooth muscle cells.

    Science.gov (United States)

    Lu, Peipei; Liu, Juntian; Pang, Xiaoming

    2015-10-01

    Atherosclerosis is a chronic inflammatory response of the arterial wall to pro‑atherosclerotic factors. As an inflammatory marker, fibrinogen directly participates in the pathogenesis of atherosclerosis. Our previous study demonstrated that fibrinogen and fibrin degradation products (FDP) produce a pro‑inflammatory effect on vascular smooth muscle cells (VSMCs) through inducing the production of interleukin‑6 (IL‑6), tumor necrosis factor‑α (TNF‑α) and inducible nitric oxide synthase (iNOS). In the present study, the effects of pravastatin on fibrinogen‑ and FDP‑induced expression of IL‑6, TNF‑α and iNOS were observed in VSMCs. The results showed that pravastatin dose‑dependently inhibited fibrinogen‑ and FDP‑stimulated expression of IL‑6, TNF‑α and iNOS in VSMCs at the mRNA and protein level. The maximal inhibition of protein expression of IL‑6, TNF‑α and iNOS was 46.9, 42.7 and 49.2% in fibrinogen‑stimulated VSMCs, and 50.2, 49.8 and 53.6% in FDP‑stimulated VSMCs, respectively. This suggests that pravastatin has the ability to relieve vascular inflammation via inhibiting the generation of IL‑6, TNF‑α and iNOS. The results of the present study may aid in further explaining the beneficial effects of pravastatin on atherosclerosis and related cardiovascular diseases. In addition, they suggest that application of pravastatin may be beneficial for prevention of atherosclerosis formation in hyperfibrinogenemia.

  20. 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.

  1. Protection of the vascular endothelium in experimental situations

    OpenAIRE

    2011-01-01

    One of the factors proposed as mediators of vascular dysfunction observed in diabetes is the increased generation of reactive oxygen species (ROS). This provides support for the use of antioxidants as early and appropriate pharmacological intervention in the development of late diabetic complications. In streptozotocin (STZ)-induced diabetes in rats we observed endothelial dysfuction manifested by reduced endothelium-dependent response to acetylcholine of the superior mesenteric artery (SMA) ...

  2. Early developmental conditions affect stress response in juvenile but not in adult house sparrows (Passer domesticus).

    Science.gov (United States)

    Lendvai, Adám Z; Loiseau, Claire; Sorci, Gabriele; Chastel, Olivier

    2009-01-01

    The short- and long-term consequences of developmental conditions on fitness have received growing attention because the environmental conditions during early life may influence growth, condition at independence, recruitment, reproductive success or survival. We tested here, in a natural house sparrow population, if early conditions during nestling stage affected the stress response of the birds (i) shortly after fledging and (ii) next year, during their first breeding. We experimentally manipulated brood size to mimic different rearing conditions, creating reduced (-2 chicks) and enlarged broods (+2 chicks), while in a third group brood size was not manipulated. Nestling nutrition state decreased with post-manipulation brood sizes as indicated by lower body mass. Fledglings with higher body mass at the age of ten days showed lower stress response than birds that were leaner at the same age. Fledglings reared in large broods showed a higher response to stress protocol than chicks from small broods, and this effect was in significant interaction with the age of fledglings at capture. This interaction indicates that the effects of the brood size became gradually smaller as the fledglings grew older and were further from their nestling period. The effects of early conditions vanished by the next year: the stress response of adult first time breeders was unrelated to the brood size they fledged from. These results suggest that stress response may reflect the actual state of an individual, rather than its developmental history.

  3. Effect of Dietary Conjugated Linoleic Acid Supplementation on Early Inflammatory Responses during Cutaneous Wound Healing

    Directory of Open Access Journals (Sweden)

    Na-Young Park

    2010-01-01

    Full Text Available Inflammatory response is considered the most important period that regulates the entire healing process. Conjugated linoleic acid (CLA, a class of linoleic acid positional and geometric isomers, is well known for its antioxidant and anti-inflammatory properties. We hypothesized that dietary CLA supplementation accelerates cutaneous wound healing by regulating antioxidant and anti-inflammatory functions. To investigate wound closure rates and inflammatory responses, we used a full-thickness excisional wound model after 2-week treatments with control, 0.5%, or 1% CLA-supplemented diet. Mice fed dietary CLA supplementation had reduced levels of oxidative stress and inflammatory markers. Moreover, the wound closure rate was improved significantly in mice fed a 1% CLA-supplemented diet during early stage of wound healing (inflammatory stage. We conclude that dietary CLA supplementation enhances the early stage of cutaneous wound healing as a result of modulating oxidative stress and inflammatory responses.

  4. Early redox, Src family kinase, and calcium signaling integrate wound responses and tissue regeneration in zebrafish.

    Science.gov (United States)

    Yoo, Sa Kan; Freisinger, Christina M; LeBert, Danny C; Huttenlocher, Anna

    2012-10-15

    Tissue injury can lead to scar formation or tissue regeneration. How regenerative animals sense initial tissue injury and transform wound signals into regenerative growth is an unresolved question. Previously, we found that the Src family kinase (SFK) Lyn functions as a redox sensor in leukocytes that detects H(2)O(2) at wounds in zebrafish larvae. In this paper, using zebrafish larval tail fins as a model, we find that wounding rapidly activated SFK and calcium signaling in epithelia. The immediate SFK and calcium signaling in epithelia was important for late epimorphic regeneration of amputated fins. Wound-induced activation of SFKs in epithelia was dependent on injury-generated H(2)O(2). A SFK member, Fynb, was responsible for fin regeneration. This work provides a new link between early wound responses and late regeneration and suggests that redox, SFK, and calcium signaling are immediate "wound signals" that integrate early wound responses and late epimorphic regeneration.

  5. 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

  6. Early changes in emotional processing as a marker of clinical response to SSRI treatment in depression.

    Science.gov (United States)

    Godlewska, B R; Browning, M; Norbury, R; Cowen, P J; Harmer, C J

    2016-11-22

    Antidepressant treatment reduces behavioural and neural markers of negative emotional bias early in treatment and has been proposed as a mechanism of antidepressant drug action. Here, we provide a critical test of this hypothesis by assessing whether neural markers of early emotional processing changes predict later clinical response in depression. Thirty-five unmedicated patients with major depression took the selective serotonin re-uptake inhibitor (SSRI), escitalopram (10 mg), over 6 weeks, and were classified as responders (22 patients) versus non-responders (13 patients), based on at least a 50% reduction in symptoms by the end of treatment. The neural response to fearful and happy emotional facial expressions was assessed before and after 7 days of treatment using functional magnetic resonance imaging. Changes in the neural response to these facial cues after 7 days of escitalopram were compared in patients as a function of later clinical response. A sample of healthy controls was also assessed. At baseline, depressed patients showed greater activation to fear versus happy faces than controls in the insula and dorsal anterior cingulate. Depressed patients who went on to respond to the SSRI had a greater reduction in neural activity to fearful versus happy facial expressions after just 7 days of escitalopram across a network of regions including the anterior cingulate, insula, amygdala and thalamus. Mediation analysis confirmed that the direct effect of neural change on symptom response was not mediated by initial changes in depressive symptoms. These results support the hypothesis that early changes in emotional processing with antidepressant treatment are the basis of later clinical improvement. As such, early correction of negative bias may be a key mechanism of antidepressant drug action and a potentially useful predictor of therapeutic response.

  7. 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.

  8. Evasion of early innate immune response by 2'-O-methylation of dengue genomic RNA.

    Science.gov (United States)

    Chang, David C; Hoang, Long T; Mohamed Naim, Ahmad Nazri; Dong, Hongping; Schreiber, Mark J; Hibberd, Martin L; Tan, Min Jie Alvin; Shi, Pei-Yong

    2016-12-01

    Dengue virus (DENV) is the most prevalent mosquito-borne virus pathogen in humans. There is currently no antiviral therapeutic or widely available vaccine against dengue infection. The DENV RNA genome is methylated on its 5' cap by its NS5 protein. DENV bearing a single E216A point mutation in NS5 loses 2'-O-methylation of its genome. While this mutant DENV is highly attenuated and immunogenic, the mechanism of this attenuation has not been elucidated. In this study, we find that replication of this mutant DENV is attenuated very early during infection. This early attenuation is not dependent on a functional type I interferon response and coincides with early activation of the innate immune response. Taken together, our data suggest that 2'-O-methylation of DENV genomic RNA is important for evasion of the host immune response during the very early stages of infection as the virus seeks to establish infection. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Chronic distress and acute vascular stress responses associated with ambulatory blood pressure in low-testosterone African men: the SABPA Study.

    Science.gov (United States)

    Malan, N T; Stalder, T; Schlaich, M P; Lambert, G W; Hamer, M; Schutte, A E; Huisman, H W; Schutte, R; Smith, W; Mels, C M C; van Rooyen, J M; Malan, L

    2014-06-01

    It is known that low testosterone (T) and high cortisol levels are associated with hypertension as well as with chronic stress, linking stress with elevated blood pressure (BP). However, the association between acute stress-, chronic stress responses and BP is not clear in Africans. Therefore, we examined the association between cortisol, psychological distress and BP responses in low- and high-T male subgroups. Beat-to-beat and ambulatory blood pressure (ABPM) and electrocardiogram measures were obtained. Serum samples were collected and analyzed for sex hormones and cortisol. Chronic psychological distress was verified with the General Health Questionnaire and acute stress with the cold pressor test. More chronic psychological distress was observed in both low- and high-T Africans compared with the Caucasians. The low-T Africans tended to have more ischemic events (P=0.06) and ABPM values (P⩽0.01) than any of the other groups. Both chronic distress (cortisol) and acute stress (total peripheral resistance cold pressor responses) were associated with ABPM in the low-T African group. Acute and chronic stress may contribute to increased BP in low-T African men. Their cortisol and vascular responses supported a tendency for ischemia, increasing their risk for coronary artery disease.

  10. Proliferation, behavior, and cytokine gene expression of human umbilical vascular endothelial cells in response to different titanium surfaces.

    Science.gov (United States)

    An, Na; Schedle, Andreas; Wieland, Marco; Andrukhov, Oleh; Matejka, Michael; Rausch-Fan, Xiaohui

    2010-04-01

    Success of dental implantation is initially affected by wound healing of both, hard and soft tissues. Endothelial cells (ECs) are involved as crucial cells in the angiogenesis and inflammation process of wound healing. In the present study, proliferation, mobility, cluster formation, and gene expression of angiogenesis-related molecules of human umbilical vascular endothelial cells (HUVECs) were investigated on titanium surfaces with different roughnesses: acid-etched (A), coarse-grit-blasted and acid-etched (SLA) surfaces, as well as on hydrophilic modified modA and modSLA surfaces. Cell behaviors were analyzed by proliferation assay and time-lapse microscopy, gene expression was analyzed by real time PCR. Results showed that cell proliferation, mobility, and cluster formation were highest on modA surfaces compared with all other surfaces. HUVECs moved slowly and exhibited seldom cell aggregation on SLA and modSLA surfaces during the whole observing period of 120 h. The gene expressions of the angiogenesis-related factors von Willebrand factor, thrombomodulin, endothelial cell protein C receptor, and adhesion molecules intercellular adhesion molecule-1 and E-selectin were most enhanced on modSLA surfaces. These results suggest that modA surface is optimal for proliferation and angiogenic behavior of ECs. However, modSLA surface seems to promote ECs to express angiogenesis-related factor genes, which play essential roles in controlling inflammation and revascularization of wound healing.

  11. Vascular response to angiotensin II predicts long-term prognosis in patients undergoing coronary artery bypass grafting

    NARCIS (Netherlands)

    Harst, van der Pim; Volbeda, M.; Voors, Adriaan; Buikema, Hendrik; Wassmann, S.; Bohm, M.; Nickenig, G.; van Gilst, W.H.

    2004-01-01

    Persistent activation of the renin-angiotensin system leads to downregulation of the angiotensin type-1 receptor, and consequently, to a decreased response to exogenous angiotensin II. In the present study, we investigated the association of angiotensin II responsiveness to clinical outcome after co

  12. Implementation of an Alert and Response System in Haiti during the Early Stage of the Response to the Cholera Epidemic

    Science.gov (United States)

    Santa-Olalla, Patricia; Gayer, Michelle; Magloire, Roc; Barrais, Robert; Valenciano, Marta; Aramburu, Carmen; Poncelet, Jean Luc; Gustavo Alonso, Juan Carlos; Van Alphen, Dana; Heuschen, Florence; Andraghetti, Roberta; Lee, Robert; Drury, Patrick; Aldighieri, Sylvain

    2013-01-01

    The start of the cholera epidemic in Haiti quickly highlighted the necessity of the implementation of an Alert and Response (A&R) System to complement the existing national surveillance system. The national system had been able to detect and confirm the outbreak etiology but required external support to monitor the spread of cholera and coordinate response, because much of the information produced was insufficiently timely for real-time monitoring and directing of a rapid, targeted response. The A&R System was designed by the Pan American Health Organization/World Health Organization in collaboration with the Haiti Ministry of Health, and it was based on a network of partners, including any institution, structure, or individual that could identify, verify, and respond to alerts. The defined objectives were to (1) save lives through early detection and treatment of cases and (2) control the spread through early intervention at the community level. The operational structure could be broken down into three principle categories: (1) alert (early warning), (2) verification and assessment of the information, and (3) efficient and timely response in coordination with partners to avoid duplication. Information generated by the A&R System was analyzed and interpreted, and the qualitative information was critical in qualifying the epidemic and defining vulnerable areas, particularly because the national surveillance system reported incomplete data for more than one department. The A&R System detected a number of alerts unrelated to cholera and facilitated rapid access to that information. The sensitivity of the system and its ability to react quickly was shown in May of 2011, when an abnormal increase in alerts coming from several communes in the Sud-Est Department in epidemiological weeks (EWs) 17 and 18 were noted and disseminated network-wide and response activities were implemented. The national cholera surveillance system did not register the increase until EWs 21 and

  13. Implementation of an alert and response system in Haiti during the early stage of the response to the cholera epidemic.

    Science.gov (United States)

    Santa-Olalla, Patricia; Gayer, Michelle; Magloire, Roc; Barrais, Robert; Valenciano, Marta; Aramburu, Carmen; Poncelet, Jean Luc; Gustavo Alonso, Juan Carlos; Van Alphen, Dana; Heuschen, Florence; Andraghetti, Roberta; Lee, Robert; Drury, Patrick; Aldighieri, Sylvain

    2013-10-01

    The start of the cholera epidemic in Haiti quickly highlighted the necessity of the implementation of an Alert and Response (A&R) System to complement the existing national surveillance system. The national system had been able to detect and confirm the outbreak etiology but required external support to monitor the spread of cholera and coordinate response, because much of the information produced was insufficiently timely for real-time monitoring and directing of a rapid, targeted response. The A&R System was designed by the Pan American Health Organization/World Health Organization in collaboration with the Haiti Ministry of Health, and it was based on a network of partners, including any institution, structure, or individual that could identify, verify, and respond to alerts. The defined objectives were to (1) save lives through early detection and treatment of cases and (2) control the spread through early intervention at the community level. The operational structure could be broken down into three principle categories: (1) alert (early warning), (2) verification and assessment of the information, and (3) efficient and timely response in coordination with partners to avoid duplication. Information generated by the A&R System was analyzed and interpreted, and the qualitative information was critical in qualifying the epidemic and defining vulnerable areas, particularly because the national surveillance system reported incomplete data for more than one department. The A&R System detected a number of alerts unrelated to cholera and facilitated rapid access to that information. The sensitivity of the system and its ability to react quickly was shown in May of 2011, when an abnormal increase in alerts coming from several communes in the Sud-Est Department in epidemiological weeks (EWs) 17 and 18 were noted and disseminated network-wide and response activities were implemented. The national cholera surveillance system did not register the increase until EWs 21 and

  14. 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.

  15. 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.

  16. 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

  17. 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

    2017-06-21

    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.

  18. Nur77 and FHL2: Novel players in vascular and immune disease

    NARCIS (Netherlands)

    Kurakula, K.B.

    2015-01-01

    The nuclear receptor Nur77 is an early response gene that is induced by diverse extracellular signals in a wide range of tissues and cultured cells. It has been implicated in the regulation of genes involved in metabolic disease, adipogenesis, inflammation, and vascular disease. FHL2/DRAL/SLIM3 is a

  19. Cathepsin K Deficiency Prevents the Aggravated Vascular Remodeling Response to Flow Cessation in ApoE-/- Mice

    OpenAIRE

    Marjo M P C Donners; Bai, Lili; Lutgens, Suzanne P. M.; Wijnands, Erwin; Johnson, Jason; Schurgers, Leon J.; Liu, Cong-Lin; Daemen, Mat; Cleutjens, Kitty B.J.M.; Shi, Guo-Ping; BIESSEN, Erik; Heeneman, Sylvia

    2016-01-01

    Cathepsin K (catK) is a potent lysosomal cysteine protease involved in extracellular matrix (ECM) degradation and inflammatory remodeling responses. Here we have investigated the contribution of catK deficiency on carotid arterial remodeling in response to flow cessation in apoE-/- and wild type (wt) background. Ligation-induced hyperplasia is considerably aggravated in apoE-/- versus wt mice. CatK protein expression was significantly increased in neointimal lesions of apoE-/- compared with w...

  20. Targeting the gut vascular endothelium induces gut effector CD8 T cell responses via cross-presentation by dendritic cells.

    Science.gov (United States)

    Bourges, Dorothee; Zhan, Yifan; Brady, Jamie L; Braley, Hal; Caminschi, Irina; Prato, Sandro; Villadangos, José A; Lew, Andrew M

    2007-11-01

    Systemic delivery of Ag usually induces poor mucosal immunity. To improve the CD8 T cell response at mucosal sites, we targeted the Ag to MAdCAM-1, a mucosal addressin cell adhesion molecule expressed mainly by high endothelial venules (HEV) in mesenteric lymph nodes (MLN) and Peyer's patches of gut-associated lymphoid tissue. When chemical conjugates of anti-MAdCAM-1 Ab and model Ag OVA were injected i.v., a greatly enhanced proliferative response of Ag-specific OT-I CD8 T cells was detected in MLN. This was preceded by prolonged accumulation, up to 2 wk, of the anti-MAdCAM OVA conjugate on HEV of Peyer's patches and MLN. In contrast, nontargeted OVA conjugate was very inefficient in inducing OT-I CD8 T cell proliferation in MLN and required at least 20-fold more Ag to induce a comparable response. In addition, MAdCAM targeting elicits an endogenous OVA-specific CD8 T cell response, evident by IFN-gamma production and target killing. Induced response offers protection against an OVA-expressing B cell lymphoma. We propose that the augmentation of gut CD8 T cell responses by MAdCAM targeting is due to both accumulation of Ag in the HEV and conversion of a soluble Ag to a cell-associated one, allowing cross-presentation by DCs.

  1. Influence of early gut microbiota on the maturation of childhood mucosal and systemic immune responses.

    Science.gov (United States)

    Sjögren, Y M; Tomicic, S; Lundberg, A; Böttcher, M F; Björkstén, B; Sverremark-Ekström, E; Jenmalm, M C

    2009-12-01

    Among sensitized infants, those with high, as compared with low levels, of salivary secretory IgA (SIgA) are less likely to develop allergic symptoms. Also, early colonization with certain gut microbiota, e.g. Lactobacilli and Bifidobacterium species, might be associated with less allergy development. Although animal and in vitro studies emphasize the role of the commensal gut microbiota in the development of the immune system, the influence of the gut microbiota on immune development in infants is unclear. To assess whether early colonization with certain gut microbiota species associates with mucosal and systemic immune responses i.e. salivary SIgA and the spontaneous Toll-like receptor (TLR) 2 and TLR4 mRNA expression and lipopolysaccharide (LPS)-induced cytokine/chemokine responses in peripheral blood mononuclear cells (PBMCs). Fecal samples were collected at 1 week, 1 month and 2 months after birth from 64 Swedish infants, followed prospectively up to 5 years of age. Bacterial DNA was analysed with real-time PCR using primers binding to Clostridium difficile, four species of bifidobacteria, two lactobacilli groups and Bacteroides fragilis. Saliva was collected at age 6 and 12 months and at 2 and 5 years and SIgA was measured with ELISA. The PBMCs, collected 12 months after birth, were analysed for TLR2 and TLR4 mRNA expression with real-time PCR. Further, the PBMCs were stimulated with LPS, and cytokine/chemokine responses were measured with Luminex. The number of Bifidobacterium species in the early fecal samples correlated significantly with the total levels of salivary SIgA at 6 months. Early colonization with Bifidobacterium species, lactobacilli groups or C. difficile did not influence TLR2 and TLR4 expression in PBMCs. However, PBMCs from infants colonized early with high amounts of Bacteroides fragilis expressed lower levels of TLR4 mRNA spontaneously. Furthermore, LPS-induced production of inflammatory cytokines and chemokines, e.g. IL-6 and CCL4 (MIP

  2. 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.

  3. [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.

  4. Total physical response in an early education setting : connecting literacy, movements, and families

    OpenAIRE

    Farrow, Karin Rae

    2008-01-01

    This paper documents the research and application of a new curriculum for Deaf students incorporating the theory of Asher: Total Physical Response. In the area of early education of Deaf students attempts need to be made to enhance and encourage the acquisition of American Sign Language and English. To aid in the young child's acquisition this new curriculum utilizes a method incorporating generalized movements. The addition of kinesthetic movements gives greater meaning to the new vocabulary...

  5. In vivo chemical exchange saturation transfer imaging allows early detection of a therapeutic response in glioblastoma.

    Science.gov (United States)

    Sagiyama, Koji; Mashimo, Tomoyuki; Togao, Osamu; Vemireddy, Vamsidhara; Hatanpaa, Kimmo J; Maher, Elizabeth A; Mickey, Bruce E; Pan, Edward; Sherry, A Dean; Bachoo, Robert M; Takahashi, Masaya

    2014-03-25

    Glioblastoma multiforme (GBM), which account for more than 50% of all gliomas, is among the deadliest of all human cancers. Given the dismal prognosis of GBM, it would be advantageous to identify early biomarkers of a response to therapy to avoid continuing ineffective treatments and to initiate other therapeutic strategies. The present in vivo longitudinal study in an orthotopic mouse model demonstrates quantitative assessment of early treatment response during short-term chemotherapy with temozolomide (TMZ) by amide proton transfer (APT) imaging. In a GBM line, only one course of TMZ (3 d exposure and 4 d rest) at a dose of 80 mg/kg resulted in substantial reduction in APT signal compared with untreated control animals, in which the APT signal continued to increase. Although there were no detectable differences in tumor volume, cell density, or apoptosis rate between groups, levels of Ki67 (index of cell proliferation) were substantially reduced in treated tumors. In another TMZ-resistant GBM line, the APT signal and levels of Ki67 increased despite the same course of TMZ treatment. As metabolite changes are known to occur early in the time course of chemotherapy and precede morphologic changes, these results suggest that the APT signal in glioma may be a useful functional biomarker of treatment response or degree of tumor progression. Thus, APT imaging may serve as a sensitive biomarker of early treatment response and could potentially replace invasive biopsies to provide a definitive diagnosis. This would have a major impact on the clinical management of patients with glioma.

  6. 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....

  7. Early- and Late-Onset Depression in Late Life: A Prospective Study on Clinical and Structural Brain Characteristics and Response to Electroconvulsive Therapy.

    Science.gov (United States)

    Dols, Annemiek; Bouckaert, Filip; Sienaert, Pascal; Rhebergen, Didi; Vansteelandt, Kristof; Ten Kate, Mara; de Winter, Francois-Laurent; Comijs, Hannie C; Emsell, Louise; Oudega, Mardien L; van Exel, Eric; Schouws, Sigfried; Obbels, Jasmien; Wattjes, Mike; Barkhof, Frederik; Eikelenboom, Piet; Vandenbulcke, Mathieu; Stek, Max L

    2017-02-01

    The clinical profile of late-life depression (LLD) is frequently associated with cognitive impairment, aging-related brain changes, and somatic comorbidity. This two-site naturalistic longitudinal study aimed to explore differences in clinical and brain characteristics and response to electroconvulsive therapy (ECT) in early- (EOD) versus late-onset (LOD) late-life depression (respectively onset characteristics were not different between EOD and LOD. Response to ECT was associated with late age at onset and presence of psychotic symptoms and not with structural MRI characteristics. In EOD only, the odds for a higher response were associated with a shorter index episode. The clinical profile, somatic comorbidities, and brain characteristics in LLD were similar in EOD and LOD. Nevertheless, patients with LOD showed a superior response to ECT compared with patients with EOD. Our results indicate that ECT is very effective in LLD, even in vascular burdened patients. Copyright © 2017 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

  8. Depressive symptoms and immune response to meningococcal conjugate vaccine in early adolescence.

    Science.gov (United States)

    O'Connor, Thomas G; Moynihan, Jan A; Wyman, Peter A; Carnahan, Jennifer; Lofthus, Gerry; Quataert, Sally A; Bowman, Melissa; Caserta, Mary T

    2014-11-01

    Research findings in psychoneuroimmunology document reliable, bidirectional linkages among psychological processes, the nervous system, and the immune system. However, available data are based almost entirely on animal and adult human studies; the application to children and adolescents is uncertain. We capitalized on the experimental leverage provided by a routine vaccination to examine the link between mood symptoms and the immune response to a vaccine challenge in early adolescence. One hundred twenty-six 11-year-olds for whom vaccine response data were available were assessed at prevaccination and 4 weeks, 3 months, and 6 months following vaccination; self-report ratings of depression and anxiety as well as measures of psychosocial and somatic risk were assessed prior to vaccine response. Analyses indicated that children's internalizing mood symptoms were associated with elevated and persistently higher antibody responses, with evidence extending to two of the four serogroups. The associations remained after controlling for multiple possible confounders (social class, body mass index, sleep, psychosocial risk, and pubertal status). The observed enhanced vaccine response associated with depressive and anxious symptoms in early adolescence may reflect an important developmental difference in immune system-brain interplay between adults and children, and it underscores the need for further developmental studies of psychoneuroimmunology.

  9. Susceptibility and resistance to Echinococcus granulosus infection: Associations between mouse strains and early peritoneal immune responses.

    Science.gov (United States)

    Mourglia-Ettlin, Gustavo; Merlino, Alicia; Capurro, Rafael; Dematteis, Sylvia

    2016-03-01

    In helminth infections, there are no easy associations between host susceptibility and immune responses. Interestingly, immunity to cestodes - unlike most helminths - seems to require Th1-type effectors. In this sense, we reported recently that Balb/c and C57Bl/6 mice are high and low susceptible strains, respectively, to experimental infection by Echinococcus granulosus. However, the role of the early cellular peritoneal response in such differential susceptibility is unknown. Here, we analyzed the kinetics of cytokines expression and cellular phenotypes in peritoneal cells from infected Balb/c and C57Bl/6 mice. Additionally, Principal Components Analysis (PCA) were conducted to highlight the most relevant differences between strains. Finally, the anti-parasite activities of peritoneal cells were assessed through in vitro systems. PCAs clustered C57Bl/6 mice by their early mixed IL-5/TNF-α responses and less intense expression of Th2-type cytokines. Moreover, they exhibited lower counts of eosinophils and higher numbers of macrophages and B cells. Functional studies showed that peritoneal cells from infected C57Bl/6 mice displayed greater anti-parasite activities, in accordance with higher rates of NO production and more efficient ADCC responses. In conclusion, mild Th2-responses and active cellular mechanisms are key determinants in murine resistance to E. granulosus infection, supporting the cestode immune exception among helminth parasites.

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

    KAUST Repository

    Liu, Pei

    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.

  11. Early Eocene cyclicity at the Wilkes Land Margin, Antarctica: Orbital forcing and environmental response

    Science.gov (United States)

    Roehl, U.; Bijl, P.; Jiménez, F.; Pross, J.; Contreras, L.; Tauxe, L.; Bohaty, S. M.; Bendle, J.; Brinkhuis, H.; IODP Expedition 318 Scientists

    2011-12-01

    The early Eocene Greenhouse interval (~56-49 Ma) was punctuated by multiple transient global warming events, or hyperthermals - the most prominent of which was the Paleocene-Eocene Thermal Maximum (PETM). Additional thermal maxima identified in Eocene records exhibit negative carbon isotope excursions (CIEs), carbonate dissolution horizons, and biotic perturbations, although of reduced magnitude and duration relative to the PETM. Many hyperthermals have been identified or postulated in the early Eocene, but it is unclear which of these events are normal carbon-cycle variations that occurred at orbital frequencies and which are exceptional events outside the normal range of Eocene carbon-cycle variability. Here we present a high-resolution cyclostratigraphy for a new early Eocene drillcore from the Wilkes Land Margin in direct proximity to the Antarctic continent (Site U1356 drilled during IODP Expedition 318). Site U1356 was situated in a mid-shelf setting during the early Eocene and is characterized by a superb magnetostratigraphy and a robust biostratigraphic age control. Our investigation includes XRF core scanning and ICP-MS data as well as bulk organic carbon isotope ratios (delta13Corg) in combination with the concentration of the total organic carbon (TOC). The early Eocene at Site U1356 consists of well developed cyclic claystones including the interval of magnetochron C24 which is ideal to re-evaluate the early Eocene part of the Geomagnetic Polarity Time Scale (GPTS) and to provide new insights into the environmental responses as well as orbital configuration of early Eocene climatic cycles.

  12. 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, V.

    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

  13. Acute Response of Circulating Vascular Regulating MicroRNAs during and after High-Intensity and High-Volume Cycling in Children

    Science.gov (United States)

    Kilian, Yvonne; Wehmeier, Udo F.; Wahl, Patrick; Mester, Joachim; Hilberg, Thomas; Sperlich, Billy

    2016-01-01

    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 years; 57.9 ± 9.4 ml·min−1·kg−1 peak oxygen uptake) performed one session of high intensity 4 × 4 min intervals (HIIT) at 90–95% peak power output (PPO), 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% PPO. 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. PMID:27014090

  14. 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.

  15. STAT1-dependent signal integration between IFNγ and TLR4 in vascular cells reflect pro-atherogenic responses in human atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Stefan Chmielewski

    Full Text Available Signal integration between IFNγ and TLRs in immune cells has been associated with the host defense against pathogens and injury, with a predominant role of STAT1. We hypothesize that STAT1-dependent transcriptional changes in vascular cells involved in cross-talk between IFNγ and TLR4, reflect pro-atherogenic responses in human atherosclerosis. Genome-wide investigation identified a set of STAT1-dependent genes that were synergistically affected by interactions between IFNγ and TLR4 in VSMCs. These included the chemokines Cxcl9, Ccl12, Ccl8, Ccrl2, Cxcl10 and Ccl5, adhesion molecules Cd40, Cd74, and antiviral and antibacterial genes Rsad2, Mx1, Oasl1, Gbp5, Nos2, Batf2 and Tnfrsf11a. Among the amplified genes was also Irf8, of which Ccl5 was subsequently identified as a new pro-inflammatory target in VSMCs and ECs. Promoter analysis predicted transcriptional cooperation between STAT1, IRF1, IRF8 and NFκB, with the novel role of IRF8 providing an additional layer to the overall complexity. The synergistic interactions between IFNγ and TLR4 also resulted in increased T-cell migration and impaired aortic contractility in a STAT1-dependent manner. Expression of the chemokines CXCL9 and CXCL10 correlated with STAT1 phosphorylation in vascular cells in plaques from human carotid arteries. Moreover, using data mining of human plaque transcriptomes, expression of a selection of these STAT1-dependent pro-atherogenic genes was found to be increased in coronary artery disease (CAD and carotid atherosclerosis. Our study provides evidence to suggest that in ECs and VSMCs STAT1 orchestrates a platform for cross-talk between IFNγ and TLR4, and identifies a STAT1-dependent gene signature that reflects a pro-atherogenic state in human atherosclerosis.

  16. 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.

  17. 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 BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: 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

  18. 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

  19. Sleep Moderates the Association Between Response Inhibition and Self-Regulation in Early Childhood.

    Science.gov (United States)

    Schumacher, Allyson M; Miller, Alison L; Watamura, Sarah E; Kurth, Salome; Lassonde, Jonathan M; LeBourgeois, Monique K

    2017-01-01

    Early childhood is a time of rapid developmental changes in sleep, cognitive control processes, and the regulation of emotion and behavior. This experimental study examined sleep-dependent effects on response inhibition and self-regulation, as well as whether acute sleep restriction moderated the association between these processes. Preschool children (N = 19; 45.6 ± 2.2 months; 11 female) followed a strict sleep schedule for at least 3 days before each of 2 morning behavior assessments: baseline (habitual nap/night sleep) and sleep restriction (missed nap/delayed bedtime). Response inhibition was evaluated via a go/no-go task. Twelve self-regulation strategies were coded from videotapes of children while attempting an unsolvable puzzle. We then created composite variables representing adaptive and maladaptive self-regulation strategies. Although we found no sleep-dependent effects on response inhibition or self-regulation measures, linear mixed-effects regression showed that acute sleep restriction moderated the relationship between these processes. At baseline, children with better response inhibition were more likely to use adaptive self-regulation strategies (e.g., self-talk, alternate strategies), and those with poorer response inhibition showed increased use of maladaptive self-regulation strategies (e.g., perseveration, fidgeting); however, response inhibition was not related to self-regulation strategies following sleep restriction. Our results showing a sleep-dependent effect on the associations between response inhibition and self-regulation strategies indicate that adequate sleep facilitates synergy between processes supporting optimal social-emotional functioning in early childhood. Although replication studies are needed, findings suggest that sleep may alter connections between maturing emotional and cognitive systems, which have important implications for understanding risk for or resilience to developmental psychopathology.

  20. Early error detection predicted by reduced pre-response control process: an ERP topographic mapping study.

    Science.gov (United States)

    Pourtois, Gilles

    2011-01-01

    Advanced ERP topographic mapping techniques were used to study error monitoring functions in human adult participants, and test whether proactive attentional effects during the pre-response time period could later influence early error detection mechanisms (as measured by the ERN component) or not. Participants performed a speeded go/nogo task, and made a substantial number of false alarms that did not differ from correct hits as a function of behavioral speed or actual motor response. While errors clearly elicited an ERN component generated within the dACC following the onset of these incorrect responses, I also found that correct hits were associated with a different sequence of topographic events during the pre-response baseline time-period, relative to errors. A main topographic transition from occipital to posterior parietal regions (including primarily the precuneus) was evidenced for correct hits ~170-150 ms before the response, whereas this topographic change was markedly reduced for errors. The same topographic transition was found for correct hits that were eventually performed slower than either errors or fast (correct) hits, confirming the involvement of this distinctive posterior parietal activity in top-down attentional control rather than motor preparation. Control analyses further ensured that this pre-response topographic effect was not related to differences in stimulus processing. Furthermore, I found a reliable association between the magnitude of the ERN following errors and the duration of this differential precuneus activity during the pre-response baseline, suggesting a functional link between an anticipatory attentional control component subserved by the precuneus and early error detection mechanisms within the dACC. These results suggest reciprocal links between proactive attention control and decision making processes during error monitoring.

  1. Early responses to deep brain stimulation in depression are modulated by anti-inflammatory drugs.

    Science.gov (United States)

    Perez-Caballero, L; Pérez-Egea, R; Romero-Grimaldi, C; Puigdemont, D; Molet, J; Caso, J-R; Mico, J-A; Pérez, V; Leza, J-C; Berrocoso, E

    2014-05-01

    Deep brain stimulation (DBS) in the subgenual cingulated gyrus (SCG) is a promising new technique that may provide sustained remission in resistant major depressive disorder (MDD). Initial studies reported a significant early improvement in patients, followed by a decline within the first month of treatment, an unexpected phenomenon attributed to potential placebo effects or a physiological response to probe insertion that remains poorly understood. Here we characterized the behavioural antidepressant-like effect of DBS in the rat medial prefrontal cortex, focusing on modifications to rodent SCG correlate (prelimbic and infralimbic (IL) cortex). In addition, we evaluated the early outcome of DBS in the SCG of eight patients with resistant MDD involved in a clinical trial. We found similar antidepressant-like effects in rats implanted with electrodes, irrespective of whether they received electrical brain stimulation or not. This effect was due to regional inflammation, as it was temporally correlated with an increase of glial-fibrillary-acidic-protein immunoreactivity, and it was blocked by anti-inflammatory drugs. Indeed, inflammatory mediators and neuronal p11 expression also changed. Furthermore, a retrospective study indicated that the early response of MDD patients subjected to DBS was poorer when they received anti-inflammatory drugs. Our study demonstrates that electrode implantation up to the IL cortex is sufficient to produce an antidepressant-like effect of a similar magnitude to that observed in rats receiving brain stimulation. Moreover, both preclinical and clinical findings suggest that the use of anti-inflammatory drugs after electrode implantation may attenuate the early anti-depressive response in patients who are subjected to DBS.

  2. Very rapid virologic response and early HCV response kinetics, as quick measures to compare efficacy and guide a personalized response-guided therapy

    Science.gov (United States)

    Yakoot, Mostafa; Abdo, Alaa M; Yousry, Ahmed; Helmy, Sherine

    2016-01-01

    Background This is the second and final report for our study designed to compare two generic sofosbuvir products for the degree and speed of virologic response to a dual anti-hepatitis C virus (HCV) treatment protocol. We aimed to test the applicability of the early virus response kinetics and the very rapid virologic response (vRVR) rate as quick outcome measures for accelerated comparative efficacy studies and as a foundation for a personalized response-guided therapy. Methods Fifty eligible chronic HCV patients were randomized to either one of two generic sofosbuvir products (Gratisovir or Grateziano) at a daily dose of one 400 mg tablet plus a weight-based ribavirin dose. Data were compared between the groups for early virus response kinetics and vRVR rates in relation to the rates of final sustained virologic response at week 12 posttreatment (SVR12). Results The Log10 transformed virus load (Log polymerase chain reaction) curves showed fairly similar rapid decline during the first 2 weeks, with no significant difference between the groups at four analysis points throughout the study by repeated-measures factorial analysis of variance test (P=0.48). The SVR12 rates were 96% (95% confidence interval, 79.6%–99.9%) in Gratisovir group (24/25) and 95.7% (95% confidence interval, 78%–99.9%) in Grateziano group (22/23). There was no statistically significant difference found by exact test (P>0.999). There was a significant association between the vRVR and the SVR12, with 100% positive predictive value (38/38 of those who had vRVR, achieved a final SVR12) and 82.6% sensitivity (among the total 46 with SVR12, 38 were having vRVR). Conclusion We can conclude from our study that the early HCV response kinetics and the vRVR rates could be used as sensitive quick markers for efficacy (with a very high positive predictive value for SVR12), based on our accelerated comparative efficacy research model. This might open the way for new models of accelerated equivalence

  3. Acidosis activation of the proton-sensing GPR4 receptor stimulates vascular endothelial cell inflammatory responses revealed by transcriptome analysis.

    Directory of Open Access Journals (Sweden)

    Lixue Dong

    Full Text Available Acidic tissue microenvironment commonly exists in inflammatory diseases, tumors, ischemic organs, sickle cell disease, and many other pathological conditions due to hypoxia, glycolytic cell metabolism and deficient blood perfusion. However, the molecular mechanisms by which cells sense and respond to the acidic microenvironment are not well understood. GPR4 is a proton-sensing receptor expressed in endothelial cells and other cell types. The receptor is fully activated by acidic extracellular pH but exhibits lesser activity at the physiological pH 7.4 and minimal activity at more alkaline pH. To delineate the function and signaling pathways of GPR4 activation by acidosis in endothelial cells, we compared the global gene expression of the acidosis response in primary human umbilical vein endothelial cells (HUVEC with varying level of GPR4. The results demonstrated that acidosis activation of GPR4 in HUVEC substantially increased the expression of a number of inflammatory genes such as chemokines, cytokines, adhesion molecules, NF-κB pathway genes, and prostaglandin-endoperoxidase synthase 2 (PTGS2 or COX-2 and stress response genes such as ATF3 and DDIT3 (CHOP. Similar GPR4-mediated acidosis induction of the inflammatory genes was also noted in other types of endothelial cells including human lung microvascular endothelial cells and pulmonary artery endothelial cells. Further analyses indicated that the NF-κB pathway was important for the acidosis/GPR4-induced inflammatory gene expression. Moreover, acidosis activation of GPR4 increased the adhesion of HUVEC to U937 monocytic cells under a flow condition. Importantly, treatment with a recently identified GPR4 antagonist significantly reduced the acidosis/GPR4-mediated endothelial cell inflammatory response. Taken together, these results show that activation of GPR4 by acidosis stimulates the expression of a wide range of inflammatory genes in endothelial cells. Such inflammatory response can be

  4. Acidosis Activation of the Proton-Sensing GPR4 Receptor Stimulates Vascular Endothelial Cell Inflammatory Responses Revealed by Transcriptome Analysis

    Science.gov (United States)

    Dong, Lixue; Li, Zhigang; Leffler, Nancy R.; Asch, Adam S.; Chi, Jen-Tsan; Yang, Li V.

    2013-01-01

    Acidic tissue microenvironment commonly exists in inflammatory diseases, tumors, ischemic organs, sickle cell disease, and many other pathological conditions due to hypoxia, glycolytic cell metabolism and deficient blood perfusion. However, the molecular mechanisms by which cells sense and respond to the acidic microenvironment are not well understood. GPR4 is a proton-sensing receptor expressed in endothelial cells and other cell types. The receptor is fully activated by acidic extracellular pH but exhibits lesser activity at the physiological pH 7.4 and minimal activity at more alkaline pH. To delineate the function and signaling pathways of GPR4 activation by acidosis in endothelial cells, we compared the global gene expression of the acidosis response in primary human umbilical vein endothelial cells (HUVEC) with varying level of GPR4. The results demonstrated that acidosis activation of GPR4 in HUVEC substantially increased the expression of a number of inflammatory genes such as chemokines, cytokines, adhesion molecules, NF-κB pathway genes, and prostaglandin-endoperoxidase synthase 2 (PTGS2 or COX-2) and stress response genes such as ATF3 and DDIT3 (CHOP). Similar GPR4-mediated acidosis induction of the inflammatory genes was also noted in other types of endothelial cells including human lung microvascular endothelial cells and pulmonary artery endothelial cells. Further analyses indicated that the NF-κB pathway was important for the acidosis/GPR4-induced inflammatory gene expression. Moreover, acidosis activation of GPR4 increased the adhesion of HUVEC to U937 monocytic cells under a flow condition. Importantly, treatment with a recently identified GPR4 antagonist significantly reduced the acidosis/GPR4-mediated endothelial cell inflammatory response. Taken together, these results show that activation of GPR4 by acidosis stimulates the expression of a wide range of inflammatory genes in endothelial cells. Such inflammatory response can be suppressed by

  5. A New Experimental Polytrauma Model in Rats: Molecular Characterization of the Early Inflammatory Response

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    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. Treatment of Glucocorticoids Inhibited Early Immune Responses and Impaired Cardiac Repair in Adult Zebrafish.

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    Wei-Chang Huang

    Full Text Available Myocardial injury, such as myocardial infarction (MI, can lead to drastic heart damage. Zebrafish have the extraordinary ability to regenerate their heart after a severe injury. Upon ventricle resection, fibrin clots seal the wound and serve as a matrix for recruiting myeloid-derived phagocytes. Accumulated neutrophils and macrophages not only reduce the risk of infection but also secrete cytokines and growth factors to promote tissue repair. However, the underlying cellular and molecular mechanisms for how immune responses are regulated during the early stages of cardiac repair are still unclear. We investigated the role and programming of early immune responses during zebrafish heart regeneration. We found that zebrafish treated with an anti-inflammatory glucocorticoid had significantly reduced heart regenerative capacities, consistent with findings in other higher vertebrates. Moreover, inhibiting the inflammatory response led to excessive collagen deposition. A microarray approach was used to assess the differential expression profiles between zebrafish hearts with normal or impaired healing. Combining cytokine profiling and immune-staining, our data revealed that impaired heart regeneration could be due to reduced phagocyte recruitment, leading to diminished angiogenesis and cell proliferation post-cardiac injury. Despite their robust regenerative ability, our study revealed that glucocorticoid treatment could effectively hinder cardiac repair in adult zebrafish by interfering with the inflammatory response. Our findings may help to clarify the initiation of cardiac repair, which could be used to develop a therapeutic intervention that may enhance cardiac repair in humans to compensate for the loss of cardiomyocytes after an MI.

  7. Histochemical characterization of early response to Cochliobolus sativus infection in selected barley genotypes.

    Science.gov (United States)

    Rodríguez-Decuadro, Susana; Silva, Paula; Bentancur, Oscar; Gamba, Fernanda; Pritsch, Clara

    2014-07-01

    Much effort is being made to breed barley with durable resistance to leaf spot blotch incited by Bipolaris sorokiniana (teleomorph: Cochliobolus sativus). We hypothesized that susceptibility and resistance traits in 11 diverse barley genotypes inoculated with a single C. sativus isolate might specify a range of distinct host cell responses. Quantitative descriptions of interaction microphenotypes exhibited by different barley genotype seedlings after infection with C. sativus are provided. Early oxidative responses occurring in epidermis and mesophyll leaf tissue were monitored by histochemical analysis of H2O2 accumulation at 8, 24, and 48 h after inoculation. Cell wall apposition (CWA) in epidermal cells and hypersensitive reaction (HR) of epidermal or mesophyll tissue were early defenses in both resistant and susceptible genotypes. There were differences in level, duration, and frequency of occurrence for CWA and HR for the different barley genotypes. Occurrence of HR in epidermal cells at post-penetration stages was indicative of compatibility. Patterns of cell responses were microphenotypically diverse between different resistant and susceptible genotypes. This suggests that timing and level of response are key features of microphenotypic diversity that distinguish different functional mechanisms of resistance and susceptibility present in barley.

  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.

    2015-01-01

    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

  9. 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.

  10. Vascular smooth muscle cell glycocalyx mediates shear stress-induced contractile responses via a Rho kinase (ROCK)-myosin light chain phosphatase (MLCP) pathway.

    Science.gov (United States)

    Kang, Hongyan; Liu, Jiajia; Sun, Anqiang; Liu, Xiao; Fan, Yubo; Deng, Xiaoyan

    2017-02-13

    The vascular smooth muscle cells (VSMCs) are exposed to interstitial flow induced shear stress that may be sensed by the surface glycocalyx, a surface layer composed primarily of proteoglycans and glycoproteins, to mediate cell contraction during the myogenic response. We, therefore, attempted to elucidate the signal pathway of the glycocalyx mechanotransduction in shear stress regulated SMC contraction. Human umbilical vein SMCs (HUVSMCs) deprived of serum for 3-4 days were exposed to a step increase (0 to 20 dyn/cm(2)) in shear stress in a parallel plate flow chamber, and reduction in the cell area was quantified as contraction. The expressions of Rho kinase (ROCK) and its downstream signal molecules, the myosin-binding subunit of myosin phosphatase (MYPT) and the myosin light chain 2 (MLC2), were evaluated. Results showed that the exposure of HUVSMCs to shear stress for 30 min induced cell contraction significantly, which was accompanied by ROCK1 up-regulation, re-distribution, as well as MYPT1 and MLC activation. However, these shear induced phenomenon could be completely abolished by heparinase III or Y-27632 pre-treatment. These results indicate shear stress induced VSMC contraction was mediated by cell surface glycocalyx via a ROCK-MLC phosphatase (MLCP) pathway, providing evidence of the glycocalyx mechanotransduction in myogenic response.

  11. Early COPD patients with lung hyperinflation associated with poorer lung function but better bronchodilator responsiveness

    Directory of Open Access Journals (Sweden)

    Chen C

    2016-10-01

    Full Text Available Chunlan Chen,* Wenhua Jian,* Yi Gao, Yanqing Xie, Yan Song, Jinping Zheng State Key Laboratory of Respiratory Disease, China National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Diseases, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Background: It is unknown whether aggressive medication strategies should be used for early COPD with or without lung hyperinflation. We aimed to explore the characteristics and bronchodilator responsiveness of early COPD patients (stages I and II with/without lung hyperinflation.Methods: Four hundred and six patients with COPD who performed both lung volume and bronchodilation tests were retrospectively analyzed. Residual volume to total lung capacity >120% of predicted values indicated lung hyperinflation. The characteristics and bronchodilator responsiveness were compared between the patients with and without lung hyperinflation across all stages of COPD.Results: The percentages of patients with lung hyperinflation were 72.7% in the entire cohort, 19.4% in stage I, 68.5% in stage II, 95.3% in stage III, and 100.0% in stage IV. The patients with lung hyperinflation exhibited poorer lung function but better bronchodilator responsiveness of both forced expiratory volume in 1 second and forced vital capacity than those without lung hyperinflation during early COPD (t=2.21–5.70, P=0.000–0.029, especially in stage I, while age, body mass index, smoking status, smoking history, and disease duration were similar between the two subgroups in the same stages. From stages I to IV of subgroups with lung hyperinflation, stage I patients had the best bronchodilator responsiveness. Use of bronchodilator responsiveness of forced vital capacity to detect the presence of lung hyperinflation in COPD patients showed relatively high sensitivities (69.5%–75.3% and specificities (70.3%

  12. Allergen-specific IL-5 responses in early childhood predict asthma at age eight.

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    Christina Weber-Chrysochoou

    Full Text Available BACKGROUND: The pattern of development of allergen-specific T cell cytokine responses in early childhood and their relation to later disease is poorly understood. Here we describe longitudinal changes in allergen-stimulated T cell cytokine responses and their relation to asthma and allergic disease during the first 8 years of life. METHODS: Subjects with a family history of asthma, who were enrolled antenatally in the Childhood Asthma Prevention Study (public trials registration number ACTRN12605000042640, had skin prick tests, clinical evaluation for asthma and eczema, and in vitro assessment of T cell cytokine responses to HDM extract performed at ages 18 months (n = 281, 3 years (n = 349, 5 years (n = 370 and 8 years (n = 275. We measured interleukin (IL- 13 at 3, 5 and 8 years, and IL-5, IL-10, and interferon-γ (IFN-γ, at 18 months, 3, 5 and 8 years by ELISA. A cohort analysis was undertaken. Independent effects of cytokine responses at each age on the risk of asthma and allergic outcomes at age 8 years were estimated by multivariable logistic regression. RESULTS: HDM-specific IL-5 responses increased with age. HDM-specific IL-13 and IL-10 responses peaked at age 5 years. HDM-specific IL-5 responses at 3 years, 5 years and 8 years were significantly associated with the presence of asthma and atopy at 8 years. IL-13 responses at 3 years, 5 years and 8 years were significantly associated with atopy at 8 years, but this association was not independent of the effect of IL-5. Other HDM-specific cytokine responses were not independently related to asthma or eczema at 8 years. CONCLUSION: HDM-specific IL-5 responses at age 3 years or later are the best measure of T cell function for predicting asthma at age 8 years.

  13. Dermoscopic hemorrhagic dots: an early predictor of response of psoriasis to biologic agents

    Science.gov (United States)

    Lallas, Aimilios; Argenziano, Giuseppe; Zalaudek, Iris; Apalla, Zoe; Ardigo, Marco; Chellini, Patricia; Cordeiro, Natalia; Guimaraes, Mariana; Kyrgidis, Athanassios; Lazaridou, Elizabeth; Longo, Caterina; Moscarella, Elvira; Papadimitriou, Ilias; Pellacani, Giovanni; Sotiriou, Elena; Vakirlis, Efstratios; Ioannides, Dimitrios

    2016-01-01

    Background Biologic agents are routinely used in the treatment of severe psoriasis. The evaluation of treatment response is mainly based on the physician’s global clinical assessment. Objective To investigate whether dermoscopy might enhance the assessment of response of psoriasis to treatment with biologic agents. Methods Patients with severe psoriasis scheduled to receive a biologic agent were enrolled in the study. A target lesion from each patient was clinically and dermoscopically documented at baseline and after one, two and six months. The clinical response was evaluated by the recruiting clinicians at all visits, while dermoscopic images were evaluated by two independent investigators, blinded to the clinical information. Chi Square test was used for cross-tabulation comparisons, while odds ratios, 95% confidence intervals and p values were calculated using univariate logistic regression. Results Overall, there was a significant correlation between clinical response and vessel distribution at all time points: a regular vessel distribution correlated with no response, a clustered distribution with partial response, and the dermoscopic absence of vessels with complete response. The presence of dermoscopic hemorrhagic dots was a potent predictor of favorable clinical response at the subsequent visit at all time points. Among lesions initially clinically responding and later recurring, 87.5% displayed dermoscopic dotted vessels despite the macroscopic remission. Conclusion Dermoscopy might be a useful additional tool for evaluating the response of psoriatic patients to biologic agents. Hemorrhagic dots represent an early predictor of clinical response, while the persistence or reappearance of dotted vessels might predict clinical persistence or recurrence, respectively. PMID:27867739

  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. The Role of Early Growth Response 1 (EGR1) in Brain Plasticity and Neuropsychiatric Disorders

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    Duclot, Florian; Kabbaj, Mohamed

    2017-01-01

    It is now clearly established that complex interactions between genes and environment are involved in multiple aspects of neuropsychiatric disorders, from determining an individual’s vulnerability to onset, to influencing its response to therapeutic intervention. In this perspective, it appears crucial to better understand how the organism reacts to environmental stimuli and provide a coordinated and adapted response. In the central nervous system, neuronal plasticity and neurotransmission are among the major processes integrating such complex interactions between genes and environmental stimuli. In particular, immediate early genes (IEGs) are critical components of these interactions as they provide the molecular framework for a rapid and dynamic response to neuronal activity while opening the possibility for a lasting and sustained adaptation through regulation of the expression of a wide range of genes. As a result, IEGs have been tightly associated with neuronal activity as well as a variety of higher order processes within the central nervous system such as learning, memory and sensitivity to reward. The immediate early gene and transcription factor early growth response 1 (EGR1) has thus been revealed as a major mediator and regulator of synaptic plasticity and neuronal activity in both physiological and pathological conditions. In this review article, we will focus on the role of EGR1 in the central nervous system. First, we will summarize the different factors influencing its activity. Then, we will analyze the amount of data, including genome-wide, that has emerged in the recent years describing the wide variety of genes, pathways and biological functions regulated directly or indirectly by EGR1. We will thus be able to gain better insights into the mechanisms underlying EGR1’s functions in physiological neuronal activity. Finally, we will discuss and illustrate the role of EGR1 in pathological states with a particular interest in cognitive functions

  16. Expression Changes of Early Response Genes in Lung Due to High Volume Ventilation

    Institute of Scientific and Technical Information of China (English)

    WANG Yuelan; YAO Shanglong; XIONG Ping

    2005-01-01

    Summary: The expression changes of early response genes due to ventilation with high volume in adult rats in vivo were observed. Forty SD male rats were randomly divided into control and 30, 60, 90 and 120 min ventilation groups, respectively (n=8 in each group). The animals were ventilated with tidal volume of 42 ml/kg and a PEEP level of 0 cmH2O at a rate of 40 breaths per minute in room air with a ventilator was given to the small animals. The expression of Egr-1, C-jun and IL-1β mRNA and proteins was detected by RT-PCR and immunohistochemical technique, respectively. The pathological changes in lung tissues were examined by HE staining. The results indicated that the expression of Egr-1, C-jun and IL-1β mRNA was detectable at 30th min after overventilation, but there was no significant difference in comparison with that in control group until overventilation for 60 min. However, at 90 and 120 min there was a significent increase as compared with 30 min or control group (P<0.05). The expression of Egr-1, C-jun and IL-1β deteced by immunohistochemical assay also showed a similar tendency of the gradual increase. In the 120 min ventilation group, the expression intensity of Egr-1, C-jun and IL-1β proteins in lung cells was the strongest and the nuclear translocation was increased markedly in comparison with any other groups (P<0.05). HE staining suggested that the degree of lung injury was aggravated gradually with the ventialtion going on and had a similar tendency to the expression of these early response genes and proteins. The current data suggested that overventilation activated and upregulated the expression of early response genes and the expression of these genes may be taken as the early signal to predict the onset and degree of lung injury. These results may demonstrated partially that the expression of early response genes induced by the mechanical stretch is associated with biochamic lung injury.

  17. Estrogen deprivation does not affect vascular heat shock response in female rats: a comparison with oxidative stress markers.

    Science.gov (United States)

    Miragem, Antônio Azambuja; Ludwig, Mirna Stela; Heck, Thiago Gomes; Baldissera, Fernanda Giesel; dos Santos, Analu Bender; Frizzo, Matias Nunes; Homem de Bittencourt, Paulo Ivo

    2015-09-01

    Hot flashes, which involve a tiny rise in core temperature, are the most common complaint of peri- and post-menopausal women, being tightly related to decrease in estrogen levels. On the other hand, estradiol (E2) induces the expression of HSP72, a member of the 70 kDa family of heat shock proteins (HSP70), which are cytoprotective, cardioprotective, and heat inducible. Since HSP70 expression is compromised in age-related inflammatory diseases, we argued whether the capacity of triggering a robust heat shock (HS) response would be still present after E2 withdrawal. Hence, we studied the effects of HS treatment (hot tub) in female Wistar rats subjected to bilateral ovariectomy (OVX) after a 7-day washout period. Twelve h after HS, the animals were killed and aortic arches were surgically excised for molecular analyses. The results were compared with oxidative stress markers in the plasma (superoxide dismutase, catalase, and lipoperoxidation) because HSP70 expression is also sensitive to redox regulation. Extracellular (plasma) to intracellular HSP70 ratio, an index of systemic inflammatory status, was also investigated. The results showed that HS response was preserved in OVX animals, as inferred from HSP70 expression (up to 40% rise, p oxidative stress, hematological parameters, and glycemic control either. This suggests that the lack of estrogen per se could not be solely ascribed as the unique source of low HSP70 expression as observed in long-term post-menopausal individuals. As a consequence, periodic evaluation of HSP70 status (iHSP70 vs. eHSP70) may be of clinical relevance because decreased HS response capacity is at the center of the onset of menopause-related dysfunctions.

  18. Tumor Interstitial Fluid Pressure as an Early-Response Marker for Anticancer Therapeutics

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    Stephane Ferretti

    2009-09-01

    Full Text Available Solid tumors have a raised interstitial fluid pressure (IFP due to high vessel permeability, low lymphatic drainage, poor perfusion, and high cell density around the blood vessels. To investigate tumor IFP as an early-response biomarker, we have tested the effect of seven anticancer chemotherapeutics including cytotoxics and targeted cytostatics in 13 experimental tumor models. IFP was recorded with the wick-in-needle method. Models were either ectopic or orthotopic and included mouse and rat syngeneic as well as human xenografts in nude mice. The mean basal IFP was between 4.4 and 15.2mm Hg; IFP was lowest in human tumor xenografts and highest in rat syngeneic models. Where measured, basal IFP correlated positively with relative tumor blood volume (rTBV determined by dynamic contrast-enhanced magnetic resonance imaging. Most chemotherapeutics sooner (2 or 3 days or later (6 or 7 days lowered tumor IFP significantly, and the cytotoxic patupilone caused the greatest decrease in IFP. In rat mammary orthotopic BN472 tumors, significant drug-induced decreases in IFP and rTBV correlated positively with each other for both patupilone and the cytostatic vatalanib. In the two orthotopic models studied, early decreases in IFP were significantly (P ≤ .005 correlated with late changes in tumor volume. Thus, drug-induced decreases in tumor IFP are an early marker of response to therapy, which could aid clinical development.

  19. Tumor interstitial fluid pressure as an early-response marker for anticancer therapeutics.

    Science.gov (United States)

    Ferretti, Stephane; Allegrini, Peter R; Becquet, Mike M; McSheehy, Paul Mj

    2009-09-01

    Solid tumors have a raised interstitial fluid pressure (IFP) due to high vessel permeability, low lymphatic drainage, poor perfusion, and high cell density around the blood vessels. To investigate tumor IFP as an early-response biomarker, we have tested the effect of seven anticancer chemotherapeutics including cytotoxics and targeted cytostatics in 13 experimental tumor models. IFP was recorded with the wick-in-needle method. Models were either ectopic or orthotopic and included mouse and rat syngeneic as well as human xenografts in nude mice. The mean basal IFP was between 4.4 and 15.2mm Hg; IFP was lowest in human tumor xenografts and highest in rat syngeneic models. Where measured, basal IFP correlated positively with relative tumor blood volume (rTBV) determined by dynamic contrast-enhanced magnetic resonance imaging. Most chemotherapeutics sooner (2 or 3 days) or later (6 or 7 days) lowered tumor IFP significantly, and the cytotoxic patupilone caused the greatest decrease in IFP. In rat mammary orthotopic BN472 tumors, significant drug-induced decreases in IFP and rTBV correlated positively with each other for both patupilone and the cytostatic vatalanib. In the two orthotopic models studied, early decreases in IFP were significantly (P tumor volume. Thus, drug-induced decreases in tumor IFP are an early marker of response to therapy, which could aid clinical development.

  20. 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.

  1. 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.)

  2. 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.

  3. Effects of pincainide on contractile responses and /sup 45/Ca movements in rat isolated vascular smooth muscle

    Energy Technology Data Exchange (ETDEWEB)

    Barrigon, S.; Diez, J.J.; Tamargo, J.; Tejerina, M.T.

    1985-05-08

    The effects of pincainide, a new ..beta..-amino anilide, on contractile responses and /sup 45/Ca fluxes were studied in rat aorta and on spontaneous mechanical activity in rat portal veins. Pincainide (10/sup 5/ to 10/sup 2/ M) produced a dose-dependent inhibition of noradrenaline (NA) and high K/sup +/-induced contractions. These inhibitory effects were observed with pincainide added either before or after the induced contractions. The Ca/sup 2 +/-induced contractions of K/sup +/-depolarized aorta as well as the spontaneous mechanical activity of portal veins were also inhibited by pincainide. Pincainide (5 x 10/sup 3/ M) inhibited the /sup 45/Ca influx stimulated by 10/sup 6/ M NA and increased /sup 45/Ca efflux. It was concluded that in isolated rat aorta, pincainide not only inhibited the influx of Ca/sup 2 +/ reducing the contractile responses to NA and high K/sup +/ but it also inhibited other effects related to NA-induced release of intracellular Ca/sup 2 +/ stores.

  4. Optical coherence tomography microangiography for monitoring the response of vascular perfusion to external pressure on human skin tissue

    Science.gov (United States)

    Choi, Woo June; Wang, Hequn; Wang, Ruikang K.

    2014-05-01

    Characterization of the relationship between external pressure and blood flow is important in the examination of pressure-induced disturbance in tissue microcirculation. Optical coherence tomography (OCT)-based microangiography is a promising imaging technique, capable of providing the noninvasive extraction of functional vessels within the skin tissue with capillary-scale resolution. Here, we present a feasibility study of OCT microangiography (OMAG) to evaluate changes in blood perfusion in response to externally applied pressure on human skin tissue in vivo. External force is loaded normal to the tissue surface at the nailfold region of a healthy human volunteer. An incremental force is applied step by step and then followed by an immediate release. Skin perfusion events including baseline are continuously imaged by OMAG, allowing for visualization and quantification of the capillary perfusion in the nailfold tissue. The tissue strain maps are simultaneously evaluated through the available OCT structural images to assess the relationship of the microcirculation response to the applied pressure. The results indicate that the perfusion progressively decreases with the constant increase of pressure. Reactive hyperemia occurs right after the removal of the pressure. The perfusion returns to the baseline level after a few minutes. These findings suggest that OMAG may have great potential for quantitatively assessing tissue microcirculation in the locally pressed tissue in vivo.

  5. Enzymatically-responsive pro-angiogenic peptide-releasing poly(ethylene glycol) hydrogels promote vascularization in vivo.

    Science.gov (United States)

    Van Hove, Amy H; Burke, Kathleen; Antonienko, Erin; Brown, Edward; Benoit, Danielle S W

    2015-11-10

    Therapeutic angiogenesis holds great potential for a myriad of tissue engineering and regenerative medicine approaches. While a number of peptides have been identified with pro-angiogenic behaviors, therapeutic efficacy is limited by poor tissue localization and persistence. Therefore, poly(ethylene glycol) hydrogels providing sustained, enzymatically-responsive peptide release were exploited for peptide delivery. Two pro-angiogenic peptide drugs, SPARC113 and SPARC118, from the Secreted Protein Acidic and Rich in Cysteine, were incorporated into hydrogels as crosslinking peptides flanked by matrix metalloproteinase (MMP) degradable substrates. In vitro testing confirmed peptide drug bioactivity requires sustained delivery. Furthermore, peptides retain bioactivity with residual MMP substrates present after hydrogel release. Incorporation into hydrogels achieved enzymatically-responsive bulk degradation, with peptide release in close agreement with hydrogel mass loss and released peptides retaining bioactivity. Interestingly, SPARC113 and SPARC118-releasing hydrogels had significantly different degradation time constants in vitro (1.16 and 8.77×10(-2) h(-1), respectively), despite identical MMP degradable substrates. However, upon subcutaneous implantation, both SPARC113 and SPARC118 hydrogels exhibited similar degradation constants of ~1.45×10(-2) h(-1), and resulted in significant ~1.65-fold increases in angiogenesis in vivo compared to controls. Thus, these hydrogels represent a promising pro-angiogenic approach for applications such as tissue engineering and ischemic tissue disorders.

  6. Inhibitory action of niflumic acid on noradrenaline- and 5-hydroxytryptamine-induced pressor responses in the isolated mesenteric vascular bed of the rat.

    Science.gov (United States)

    Criddle, D N; de Moura, R S; Greenwood, I A; Large, W A

    1997-03-01

    1. The effects of niflumic acid, an inhibitor of calcium-activated chloride currents, were compared with the actions of the calcium channel blocker nifedipine on noradrenaline- and 5-hydroxytryptamine (5-HT)-induced pressor responses of the rat perfused isolated mesenteric vascular bed. 2. Bolus injections of noradrenaline (1 and 10 nmol) increased the perfusion pressure in a dose-dependent manner. Nifedipine (1 microM) inhibited the increase in pressure produced by 1 nmol noradrenaline by 31 +/- 5%. Niflumic acid (10 and 30 microM) also inhibited the noradrenaline-induced increase in perfusion pressure and 30 microM niflumic acid reduced the pressor response to 1 nmol noradrenaline by 34 +/- 6%. 3. The increases in perfusion elicited by 5-HT (0.3 and 3 nmol) were reduced by niflumic acid (10 and 30 microM) in a concentration-dependent manner and 30 microM niflumic acid inhibited responses to 0.3 and 3 nmol 5-HT by, respectively, 49 +/- 8% and 50 +/- 7%. Nifedipine (1 microM) decreased the pressor response to 3 nmol 5-HT by 44 +/- 9%. 4. In the presence of a combination of 30 microM niflumic acid and 1 microM nifedipine the inhibition of the pressor effects of noradrenaline (10 nmol) and 5-HT (3 nmol) was not significantly greater than with niflumic acid (30 microM) alone. Thus the effects of niflumic acid and nifedipine were not additive. 5. In Ca-free conditions the transient contractions induced by 5-HT (3 nmol) were not reduced by 30 microM niflumic acid, suggesting that this agent does not inhibit calcium release from the intracellular store or the binding of 5-HT to its receptor. 6. Niflumic acid 30 microM did not inhibit the pressor responses induced by KCl (20 and 60 mumol) which were markedly reduced by 1 microM nifedipine. In addition, 1 microM levcromakalim decreased pressor responses produced by 20 mumol KCl. These data suggest that niflumic acid does not block directly calcium channels or activate potassium channels. 7. It is concluded that niflumic

  7. 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.

  8. 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.

  9. Response of Late Carboniferous and Early Permian Plant Communities to Climate Change

    Science.gov (United States)

    Dimichele, William A.; Pfefferkorn, Hermann W.; Gastaldo, Robert A.

    Late Carboniferous and Early Permian strata record the transition from a cold interval in Earth history, characterized by the repeated periods of glaciation and deglaciation of the southern pole, to a warm-climate interval. Consequently, this time period is the best available analogue to the Recent in which to study patterns of vegetational response, both to glacial-interglacial oscillation and to the appearance of warm climate. Carboniferous wetland ecosystems were dominated by spore-producing plants and early gymnospermous seed plants. Global climate changes, largely drying, forced vegetational changes, resulting in a change to a seed plant-dominated world, beginning first at high latitudes during the Carboniferous, reaching the tropics near the Permo-Carboniferous boundary. For most of this time plant assemblages were very conservative in their composition. Change in the dominant vegetation was generally a rapid process, which suggests that environmental thresholds were crossed, and involved little mixing of elements from the wet and dry floras.

  10. Response of Late Carboniferous and Early Permian plant communities to climate change

    Energy Technology Data Exchange (ETDEWEB)

    DiMichele, W.A.; Pfefferkorn, H.W.; Gastaldo, R.A. [Smithsonian Institute, Washington, DC (USA). National Museum of National History

    2001-07-01

    Late Carboniferous and Early Permian strata record the transition from a cold interval in Earth history, characterized by the repeated periods of glaciation and deglaciation of the southern pole, to a warm-climate interval. Consequently, this time period is the best available analogue to the Recent in which to study patterns of vegetational response, both to glacial-interglacial oscillation and to the appearance of warm climate. Carboniferous wetland ecosystems were dominated by spore-producing plants and early gymnospermous seed plants. Global climate changes, largely drying, forced vegetational changes, resulting in a change to a seed plant-dominated world, beginning first at high latitudes during the Carboniferous, reaching the tropics near the Permo-Carboniferous boundary. For most of this time plant assemblages were very conservative in their composition. Change in the dominant vegetation was generally a rapid process, which suggests that environmental thresholds were crossed, and involved little mixing of elements from the wet and dry floras.

  11. Lung function and bronchial responsiveness after Mycoplasma pneumoniae infection in early childhood

    DEFF Research Database (Denmark)

    Kjaer, B.B.; Jensen, J.S.; Nielsen, K.G.

    2008-01-01

    .17 versus 1.21 (kPa sec), P=0.45; and mean change in specific resistance was 13% versus 9%, P= 0.42. In conclusion, M. pneumoniae infection in early childhood was not associated with long-term effects on lung function and bronchial hyperresponsiveness 2 years after infection Udgivelsesdato: 2008/6......Mycoplasma (M.) pneumoniae has been associated with exacerbation of symptoms in asthmatic school children and adults; and an etiological role in asthma has been suggested. The purpose of this study was to investigate whether infection with M. pneumoniae in early childhood has a long-term influence...... on lung function and bronchial responsiveness. In a retrospective, clinical cohort-study children younger than 5 years-of-age when PCR-tested for M. pneumoniae were enrolled. Sixty-five children with clinical symptoms suggesting infection with M. pneumoniae during an epidemic season completed a clinical...

  12. Behavioral responses of leaves and vascular cambium of Prosopis cineraria (L.) Druce to different regimes of coal-smoke pollution

    Energy Technology Data Exchange (ETDEWEB)

    Iqbal, M.; Mahmooduzzafar; Aref, I.M.; Khan, P.R. [Hamdard University, New Delhi (India). Faculty of Science

    2010-07-01

    The foliar and cambial responses of Prosopis cineraria to five different coal-smoke regimes in Delhi, India, were studied using the monthly collections of leaves and cambial blocks as well as the data on SO{sub 2}, NO{sub 2} and particulate concentrations from each of the five study sites. Coal-smoke inhibited pigment concentration, NR activity and sugar content and promoted stomatal index and the nitrate and sulfur contents. Stomatal conductance was low, leading to a drop in the net photosynthetic rate. Cambial activity started quite late and the annual increment of wood was reduced despite a prolonged active phase, possibly due to a distinctly retarded rate of cambial cell division. Vessel proportion in the wood increased but the size of vessel elements and fibers decreased. Such studies may help in identifying trees suitable for cultivation in the pollution-affected areas.

  13. Activity-dependent calcium, oxygen, and vascular responses in a mouse model of familial hemiplegic migraine type 1.

    Science.gov (United States)

    Khennouf, Lila; Gesslein, Bodil; Lind, Barbara Lykke; van den Maagdenberg, Arn M J M; Lauritzen, Martin

    2016-08-01

    Familial hemiplegic migraine type 1 (FHM1) is a subtype of migraine with aura caused by a gain-of-function mutation in the pore-forming α1 subunit of CaV 2.1 (P/Q-type) calcium channels. However, the mechanisms underlying how the disease is brought about and the prolonged aura remain incompletely understood. In the anesthetized FHM1 mouse model in vivo, we used two-photon microscopy to measure calcium changes in neurons and astrocytes during somatosensory stimulations and cortical spreading depression (CSD), the putative mechanism of the migraine aura. We combined 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. During spreading depression, the evoked increase in cytosolic Ca(2+) 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, Ca(2+) and hemodynamic responses to somatosensory stimulations were smaller in FHM1 mice than WT mice and almost abolished after CSD. The CSD-induced Ca(2+) changes were mitigated by the CaV 2.1 gating modifier, tert-butyl dihydroquinone. Our findings suggest that tissue anoxia might be a mechanism for prolonged aura in FHM1. Reduced Ca(2+) signals during normal network activity in FHM1 as compared to WT mice may explain impaired neurovascular responses in the mutant, and these alterations could contribute to brain frailty in FHM1 patients. Ann Neurol 2016;80:219-232. © 2016 American Neurological Association.

  14. Early lactation feed intake and milk yield responses of dairy cows offered grass silages harvested at early maturity stages.

    Science.gov (United States)

    Randby, A T; Weisbjerg, M R; Nørgaard, P; Heringstad, B

    2012-01-01

    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 (silages were restrictedly fermented. Silage digestible organic matter in dry matter (DM) values were 747, 708, and 647 g/kg of DM for H1, H2, and H3, respectively. Dietary treatments were fed in a 3×3 factorial arrangement of the 3 silages supplemented with 3 concentrate levels (4, 8, and 12 kg/d) and, additionally, H1 was offered without concentrates and H3 with 16 kg/d, giving a total of 11 diets. Cows, blocked according to parity and calving date, were introduced to the experiment before calving and kept in the experiment until wk 16 of lactation. Silage was offered ad libitum in loose housing and concentrate 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-corrected milk (ECM) yield increased from 23.4 kg when H1 was offered without concentrate supplement to 29.1 and 32.8 kg when supplemented with 4 or 8 kg concentrate, respectively. None of the other diets equaled the yield obtained by H1 plus 8 kg of concentrate. Feed intake and yield of cows offered H3 plus 4 kg of concentrates were strongly constrained by high dietary fiber concentration. They consumed 16.5 g of neutral detergent fiber/kg of body weight and spent more time eating silage than cows offered other diets. The highest

  15. Full-Breadth Analysis of CD8+ T-Cell Responses in Acute Hepatitis C Virus Infection and Early Therapy

    Science.gov (United States)

    Lauer, Georg M.; Lucas, Michaela; Timm, Joerg; Ouchi, Kei; Kim, Arthur Y.; Day, Cheryl L.; zur Wiesch, Julian Schulze; Paranhos-Baccala, Glaucia; Sheridan, Isabelle; Casson, Deborah R.; Reiser, Markus; Gandhi, Rajesh T.; Li, Bin; Allen, Todd M.; Chung, Raymond T.; Klenerman, Paul; Walker, Bruce D.

    2005-01-01

    Multispecific CD8+ T-cell responses are thought to be important for the control of acute hepatitis C virus (HCV) infection, but to date little information is actually available on the breadth of responses at early time points. Additionally, the influence of early therapy on these responses and their relationships to outcome are controversial. To investigate this issue, we performed comprehensive analysis of the breadth and frequencies of virus-specific CD8+ T-cell responses on the single epitope level in eight acutely infected individuals who were all started on early therapy. During the acute phase, responses against up to five peptides were identified. During therapy, CD8+ T-cell responses decreased rather than increased as virus was controlled, and no new specificities emerged. A sustained virological response following completion of treatment was independent of CD8+ T-cell responses, as well as CD4+ T-cell responses. Rapid recrudescence also occurred despite broad CD8+ T-cell responses. Importantly, in vivo suppression of CD3+ T cells using OKT3 in one subject did not result in recurrence of viremia. These data suggest that broad CD8+ T-cell responses alone may be insufficient to contain HCV replication, and also that early therapy is effective independent of such responses. PMID:16189000

  16. Early vs. asymptotic growth responses of herbaceous plants to elevated CO[sub 2

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, S.C.; Jasienski, M.; Bazzaz, F.A. (Harvard Univ., Cambridge, MA (United States). Dept. of Organismic and Evolutionary Biology)

    1999-07-01

    Although many studies have examined the effects of elevated carbon dioxide on plant growth,'' the dynamics of growth involve at least two parameters, namely, an early rate of exponential size increase and an asymptotic size reached late in plant ontogeny. The common practice of quantifying CO[sub 2] responses as a single response ratio thus obscures two qualitatively distinct kinds of effects. The present experiment examines effects of elevated CO[sub 2] on both early and asymptotic growth parameters in eight C[sub 3] herbaceous plant species (Abutilon theophrasti, Cassia obtusifolia, Plantago major, Rumex crispus, Taraxacum officinale, Dactylis glomerata, Lolium multiflorum, and Panicum dichotomoflorum). Plants were grown for 118--172 d in a factorial design of CO[sub 2] (350 and 700 [micro]L/L) and plant density (individually grown vs. high-density monocultures) under edaphic conditions approximating those of coastal areas in Massachusetts. For Abutilon theophrasti, intraspecific patterns of plant response were also assessed using eight genotypes randomly sampled from a natural population and propagated as inbred lines.

  17. 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.

  18. 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.

  19. 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.