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Sample records for evoke distinct endothelial

  1. Intraurethral stimulation evokes bladder responses via 2 distinct reflex pathways.

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    Woock, John P; Yoo, Paul B; Grill, Warren M

    2009-07-01

    Recent animal studies have shown that selective activation of pudendal nerve branches can evoke bladder responses through 2 distinct reflex pathways. We examined intraurethral electrical stimulation as a minimally invasive means of selectively activating these pathways in the cat. Bladder responses evoked by intraurethral electrical stimulation were measured in alpha-chloralose anesthetized male cats at different stimulation frequencies, stimulation intensities and intraurethral locations. Intraurethral electrical stimulation evoked inhibitory and excitatory bladder reflexes depending on stimulation frequency and location. Stimulation in the penile urethra 0 to 3 cm from the urethral meatus at 33 Hz evoked bladder contraction and at 10 Hz it evoked bladder relaxation. These responses were abolished after bilateral transection of the dorsal penile nerves. Stimulation in the membranous urethra 5 to 7 cm from the urethral meatus at 2, 10 and 33 Hz evoked bladder contractions. These responses were abolished after bilateral transection of the cranial sensory nerves. Following acute spinal cord transection bladder contractions were still evoked by 33 Hz stimulation in the penile urethra but not by stimulation at any frequency in the membranous urethra. Intraurethral electrical stimulation selectively evoked bladder responses by activating 2 distinct pudendal afferent pathways. Responses depended on stimulation frequency and location. Intraurethral electrical stimulation is a valid means of determining the pathways involved in bladder responses evoked by pudendal nerve stimulation.

  2. Different brain potentials evoked at distinct phases of rule learning.

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    Li, Fuhong; Cao, Bihua; Gao, Heming; Kuang, Li; Li, Hong

    2012-09-01

    The neural mechanisms of rule learning are of interest to cognitive neuroscientists, but the time course of rule induction and the related brain potential remain unclear. In this study, event-related brain potentials (ERPs) were measured during the distinct phases of rule induction. Participants in two experiments were presented with a series of Arabic numbers and were asked to detect the hidden rules. The ERP results revealed that (a) the rule-discovery trials elicited a larger P3 component than the nondiscovery trials, reflecting the initial identification of the regularity of number series, and (b) when a new instance was incongruent with the previously acquired rule, a larger N2 and enhanced late positive component were elicited, reflecting the process of mismatch detection and the updating of working memory context. Copyright © 2012 Society for Psychophysiological Research.

  3. Rab35 protein regulates evoked exocytosis of endothelial Weibel–Palade bodies

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    Biesemann, Anja; Gorontzi, Alexandra; Barr, Francis; Gerke, Volker

    2017-01-01

    Weibel–Palade bodies (WPB) are secretory organelles of endothelial cells that undergo evoked exocytosis following intracellular Ca2+ or cAMP elevation, thereby supplying the vasculature with factors controlling hemostasis. Several cytosolic and membrane-associated proteins, including the Rab family members Rab3, Rab15, and Rab27a, have been implicated in regulating the acute exocytosis of WPB. Here, we carried out a genome-wide screen to identify Rab pathways affecting WPB exocytosis. Overexpression of a specific subset of Rab GTPase–activating proteins (RabGAPs) inhibited histamine-evoked, Ca2+-dependent WPB exocytosis, presumably by inactivating the target Rab GTPases. Among these RabGAPs, we concentrated on TBC1D10A and showed that the inhibitory effect depends on its GAP activity. We confirmed that Rab35 was a target Rab of TBC1D10A in human endothelial cells; Rab35 interacted with TBC1D10A, and expression of the GAP-insensitive Rab35(Q67A) mutant rescued the inhibitory effect of TBC1D10A overexpression on WPB exocytosis. Furthermore, knockdown of Rab35 and expression of a dominant-negative Rab35 mutant both inhibited histamine-evoked secretion of the WPB cargos von Willebrand factor and P-selectin. Pulldown and co-immunoprecipitation experiments identified the ArfGAP with coiled-coil, Ank repeat, and pleckstrin homology domain–containing protein ACAP2 as an Rab35 effector in endothelial cells, and depletion as well as overexpression approaches revealed that ACAP2 acts as a negative regulator of WPB exocytosis. Interestingly, a known ACAP2 target, the small GTPase Arf6, supported histamine-evoked WPB exocytosis, as shown by knockdown and overexpression of a dominant-negative Arf6 mutant. Our data identify Rab35 as a novel regulator of WPB exocytosis, most likely acting through the downstream effectors ACAP2 and Arf6. PMID:28566286

  4. Rab35 protein regulates evoked exocytosis of endothelial Weibel-Palade bodies.

    Science.gov (United States)

    Biesemann, Anja; Gorontzi, Alexandra; Barr, Francis; Gerke, Volker

    2017-07-14

    Weibel-Palade bodies (WPB) are secretory organelles of endothelial cells that undergo evoked exocytosis following intracellular Ca 2+ or cAMP elevation, thereby supplying the vasculature with factors controlling hemostasis. Several cytosolic and membrane-associated proteins, including the Rab family members Rab3, Rab15, and Rab27a, have been implicated in regulating the acute exocytosis of WPB. Here, we carried out a genome-wide screen to identify Rab pathways affecting WPB exocytosis. Overexpression of a specific subset of Rab GTPase-activating proteins (RabGAPs) inhibited histamine-evoked, Ca 2+ -dependent WPB exocytosis, presumably by inactivating the target Rab GTPases. Among these RabGAPs, we concentrated on TBC1D10A and showed that the inhibitory effect depends on its GAP activity. We confirmed that Rab35 was a target Rab of TBC1D10A in human endothelial cells; Rab35 interacted with TBC1D10A, and expression of the GAP-insensitive Rab35(Q67A) mutant rescued the inhibitory effect of TBC1D10A overexpression on WPB exocytosis. Furthermore, knockdown of Rab35 and expression of a dominant-negative Rab35 mutant both inhibited histamine-evoked secretion of the WPB cargos von Willebrand factor and P-selectin. Pulldown and co-immunoprecipitation experiments identified the ArfGAP with coiled-coil, Ank repeat, and pleckstrin homology domain-containing protein ACAP2 as an Rab35 effector in endothelial cells, and depletion as well as overexpression approaches revealed that ACAP2 acts as a negative regulator of WPB exocytosis. Interestingly, a known ACAP2 target, the small GTPase Arf6, supported histamine-evoked WPB exocytosis, as shown by knockdown and overexpression of a dominant-negative Arf6 mutant. Our data identify Rab35 as a novel regulator of WPB exocytosis, most likely acting through the downstream effectors ACAP2 and Arf6. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. Involvement of iron-evoked oxidative stress in smoking-related endothelial dysfunction in healthy young men.

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    Kei Fukami

    Full Text Available BACKGROUND: Oxidative stress and smoking contribute to endothelial dysfunction. Iron might also play a role in oxidative stress generation and endothelial dysfunction. However, the involvement of iron in smoking-induced endothelial dysfunction in healthy smokers remains unclear. Therefore, we examined here whether (1 intravenous iron infusion impaired endothelial function evaluated by flow-mediated vasodilatation (FMD in non-smokers, and (2 deferoxamine, a potent iron chelator, ameliorated endothelial dysfunction in healthy smokers. METHODS: Eight healthy young male non-smokers (23 ± 4 years old received intravenous injection of saccharated ferric oxide (0.7 mg/kg body weight, while 10 age-matched healthy male smokers received deferoxamine mesylate (8.3 mg/kg body weight. At baseline, 5 and 20 minutes after treatment with iron or deferoxamine, biochemical variables were measured, including serum iron and marondialdehyde (MDA, a marker of lipid oxidation, and endothelial function was simultaneously evaluated by FMD. RESULTS: Compared with non-smokers, FMD was significantly lower in smokers. Iron and MDA levels were significantly increased, whereas FMD was impaired by iron infusion in non-smokers. Conversely, deferoxamine treatment significantly decreased iron and MDA levels and restored the decreased FMD in smokers. Baseline serum iron and MDA levels in all 18 subjects (non-smokers and smokers were correlated with each other. There was a significant inverse correlation between the changes in MDA values and FMD from baseline in 18 men. Endothelium-independent vasodilation by glyceryl trinitrate was unaltered by either treatment. CONCLUSIONS: Our present study suggests that iron-evoked oxidative stress might play a role in endothelial dysfunction in healthy smokers.

  6. Revealing the distinction between perception and cognition through intra-individual variability of visual evoked responses.

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    Constantinescu, V D

    1996-01-01

    Searching for a method to objectively detect the cognitive activity of the brain, the variability of visual evoked responses (ER) was analysed in 75 human subjects and 10 animals. The individual ERs of a normal subject were found typically very scattered in the first approx. 120 ms after stimulation, converging at 160-220 ms and then diverging again progressively. This variability pattern (VP) is event-related and is not attributable to background noise. On the other hand, statistically significant correlation showed that in most patients, with anatomically intact visual structures but with pronounced mental troubles, the VP is absent and the ERs are randomly scattered. Based on these results we consider that the event-related variability reflects the cognition function of the subjects and that it is instrumental in evidencing the distinction between cognitive and perceptive processes. The results are further consistent with the idea that cognition implies the chaotic activity of certain neural populations and that the VP reflects this chaotic, non-repetitive, non-linear and impredictable but effective neural activity.

  7. Methylglyoxal-derived hydroimidazolone-1 evokes inflammatory reactions in endothelial cells via an interaction with receptor for advanced glycation end products.

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    Ishibashi, Yuji; Matsui, Takanori; Nakamura, Nobutaka; Sotokawauchi, Ami; Higashimoto, Yuichiro; Yamagishi, Sho-Ichi

    2017-09-01

    Glyceraldehyde-derived advanced glycation end products contribute to vascular inflammation in diabetes. However, what advanced glycation end product structure could evoke inflammatory reactions remains unknown. We examined whether and how methylglyoxal-derived hydroimidazolone 1, one of the advanced glycation end products formed from glyceraldehyde, elicits inflammatory reactions in human umbilical vein endothelial cells. Glyceraldehyde-advanced glycation end products-aptamer was prepared using a systemic evolution of ligands by exponential enrichment. The binding affinities of methylglyoxal-derived hydroimidazolone 1 to receptor for advanced glycation end products or advanced glycation end product-aptamer were measured with a quartz crystal microbalance. Intracellular reactive oxygen species generation and THP-1 cell adhesion were evaluated using fluorescent probes. Gene expression was analysed by reverse transcription polymerase chain reaction. Methylglyoxal-derived hydroimidazolone 1 bound to receptor for advanced glycation end products and advanced glycation end product-aptamer with a dissociation constant ( K d ) of 56.7 µM and 1.51 mM, respectively. Methylglyoxal-derived hydroimidazolone 1 at 100 µg/mL significantly increased reactive oxygen species generation in human umbilical vein endothelial cells, which were attenuated by anti-receptor for advanced glycation end products antibody or advanced glycation end product-aptamer. In all, 100 µg/mL methylglyoxal-derived hydroimidazolone 1 significantly increased receptor for advanced glycation end products and intercellular adhesion molecule-1 messenger RNA levels in, and THP-1 cell adhesion to, human umbilical vein endothelial cells, all of which were blocked by anti-receptor for advanced glycation end products antibody. Our present results indicate that methylglyoxal-derived hydroimidazolone 1 evokes inflammatory reactions in human umbilical vein endothelial cells via receptor for advanced glycation

  8. Bradykinin-evoked changes in cytosolic calcium and membrane currents in cultured bovine pulmonary artery endothelial cells.

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    Cannell, M B; Sage, S O

    1989-12-01

    1. Cultured bovine pulmonary artery endothelial cells were voltage clamped using a single microelectrode while cytosolic free calcium concentration ([Ca2+]i) was simultaneously measured using the fluorescent calcium indicator, Indo-1. 2. The resting current-voltage relationship was non-linear and exhibited marked inward rectification near the resting potential. In about 60% of cells examined, superfusion of saline resulted in a hyperpolarization and decrease in inward current. This result did not depend on the presence of agonist and is consistent with the presence of extracellular potassium accumulation in restricted spaces around the cell and the known dependence of the inward rectifier. In other cells there was no effect. 3. Resting [Ca2+]i was sensitive to membrane potential, decreasing continuously with membrane depolarization over the range -70 to +60 mV. This result is consistent with a simple pump-leak model and suggests that voltage-dependent calcium channels are not present in these cells. 4. Bradykinin (10 microM) increased [Ca2+]i after a delay of approximately 3 s. [Ca2+]i reached a peak after a further 3 s and declined over several minutes. 5. During the rise in [Ca2+]i evoked by application of bradykinin, there were no changes in the current-voltage relationship of the cell. These results question the role of a receptor-operated non-selective cation channel in mediating the increase in [Ca2+]i. This observation, coupled with the observed delay in the agonist-evoked response suggests that a second messenger system is involved in mediating the increase in [Ca2+]i. 6. Changes in the current-voltage relation started to occur about 30 s after the application of agonist. These changes could be explained by the activation of large-conductance potassium and non-selective cation channels with a reversal potential near 0 mV. The latter channels may mediate the plateau phase of the agonist-evoked response. 7. The results are discussed with respect to the

  9. Distinct Somatic Discrimination Reflected by Laser-Evoked Potentials Using Scalp EEG Leads.

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    Hsueh, Jen-Jui; Chen, Jia-Jin Jason; Shaw, Fu-Zen

    Discrimination is an important function in pain processing of the somatic cortex. The involvement of the somatic cortex has been studied using equivalent dipole analysis and neuroimaging, but the results are inconsistent. Scalp electroencephalography (EEG) can reflect functional changes of particular brain regions underneath a lead. However, the responses of EEG leads close to the somatic cortex in response to pain have not been systematically evaluated. The present study applied CO2 laser stimulation to the dorsum of the left hand. Laser-evoked potentials (LEPs) of C4, T3, and T4 leads and pain ratings in response to four stimulus intensities were analyzed. LEPs started earlier at the C4 and T4 leads. The onset latency and peak latency of LEPs for C4 and T4 leads were the same. Only 10 of 22 subjects (45 %) presented equivalent current dipoles within the primary somatosensory or motor cortices. LEP amplitudes of these leads increased as stimulation intensity increased. The stimulus-response pattern of the C4 lead was highly correlated with pain rating. In contrast, an S-shaped stimulus-response curve was obtained for the T3 and T4 leads. The present study provides supporting evidence that particular scalp channels are able to reflect the functional characteristics of their underlying cortical areas. Our data strengthen the clinical application of somatic-cortex-related leads for pain discrimination.

  10. Mapping the distinctive populations of lymphatic endothelial cells in different zones of human lymph nodes.

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    Saem Mul Park

    Full Text Available The lymphatic sinuses in human lymph nodes (LNs are crucial to LN function yet their structure remains poorly defined. Much of our current knowledge of lymphatic sinuses derives from rodent models, however human LNs differ substantially in their sinus structure, most notably due to the presence of trabeculae and trabecular lymphatic sinuses that rodent LNs lack. Lymphatic sinuses are bounded and traversed by lymphatic endothelial cells (LECs. A better understanding of LECs in human LNs is likely to improve our understanding of the regulation of cell trafficking within LNs, now an important therapeutic target, as well as disease processes that involve lymphatic sinuses. We therefore sought to map all the LECs within human LNs using multicolor immunofluorescence microscopy to visualize the distribution of a range of putative markers. PROX1 was the only marker that uniquely identified the LECs lining and traversing all the sinuses in human LNs. In contrast, LYVE1 and STAB2 were only expressed by LECs in the paracortical and medullary sinuses in the vast majority of LNs studied, whilst the subcapsular and trabecular sinuses lacked these molecules. These data highlight the existence of at least two distinctive populations of LECs within human LNs. Of the other LEC markers, we confirmed VEGFR3 was not specific for LECs, and CD144 and CD31 stained both LECs and blood vascular endothelial cells (BECs; in contrast, CD59 and CD105 stained BECs but not LECs. We also showed that antigen-presenting cells (APCs in the sinuses could be clearly distinguished from LECs by their expression of CD169, and their lack of expression of PROX1 and STAB2, or endothelial markers such as CD144. However, both LECs and sinus APCs were stained with DCN46, an antibody commonly used to detect CD209.

  11. Decorin-evoked paternally expressed gene 3 (PEG3) is an upstream regulator of the transcription factor EB (TFEB) in endothelial cell autophagy.

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    Neill, Thomas; Sharpe, Catherine; Owens, Rick T; Iozzo, Renato V

    2017-09-29

    Macroautophagy is a fundamental and evolutionarily conserved catabolic process that eradicates damaged and aging macromolecules and organelles in eukaryotic cells. Decorin, an archetypical small leucine-rich proteoglycan, initiates a protracted autophagic program downstream of VEGF receptor 2 (VEGFR2) signaling that requires paternally expressed gene 3 (PEG3). We have discovered that PEG3 is an upstream transcriptional regulator of transcription factor EB (TFEB), a master transcription factor of lysosomal biogenesis, for decorin-evoked endothelial cell autophagy. We found a functional requirement of PEG3 for TFEB transcriptional induction and nuclear translocation in human umbilical vein endothelial and PAER2 cells. Mechanistically, inhibiting VEGFR2 or AMP-activated protein kinase (AMPK), a major decorin-activated energy sensor kinase, prevented decorin-evoked TFEB induction and nuclear localization. In conclusion, our findings indicate a non-canonical (nutrient- and energy-independent) mechanism underlying the pro-autophagic bioactivity of decorin via PEG3 and TFEB. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Vascular Endothelial Growth Factor-B Induces a Distinct Electrophysiological Phenotype in Mouse Heart

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    Nikolay Naumenko

    2017-05-01

    Full Text Available Vascular endothelial growth factor B (VEGF-B is a potent mediator of vascular, metabolic, growth, and stress responses in the heart, but the effects on cardiac muscle and cardiomyocyte function are not known. The purpose of this study was to assess the effects of VEGF-B on the energy metabolism, contractile, and electrophysiological properties of mouse cardiac muscle and cardiac muscle cells. In vivo and ex vivo analysis of cardiac-specific VEGF-B TG mice indicated that the contractile function of the TG hearts was normal. Neither the oxidative metabolism of isolated TG cardiomyocytes nor their energy substrate preference showed any difference to WT cardiomyocytes. Similarly, myocyte Ca2+ signaling showed only minor changes compared to WT myocytes. However, VEGF-B overexpression induced a distinct electrophysiological phenotype characterized by ECG changes such as an increase in QRSp time and decreases in S and R amplitudes. At the level of isolated TG cardiomyocytes, these changes were accompanied with decreased action potential upstroke velocity and increased duration (APD60–70. These changes were partly caused by downregulation of sodium current (INa due to reduced expression of Nav1.5. Furthermore, TG myocytes had alterations in voltage-gated K+ currents, namely decreased density of transient outward current (Ito and total K+ current (Ipeak. At the level of transcription, these were accompanied by downregulation of Kv channel-interacting protein 2 (Kcnip2, a known modulatory subunit for Kv4.2/3 channel. Cardiac VEGF-B overexpression induces a distinct electrophysiological phenotype including remodeling of cardiomyocyte ion currents, which in turn induce changes in action potential waveform and ECG.

  13. Microvascular coronary artery spasm presents distinctive clinical features with endothelial dysfunction as nonobstructive coronary artery disease.

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    Ohba, Keisuke; Sugiyama, Seigo; Sumida, Hitoshi; Nozaki, Toshimitsu; Matsubara, Junichi; Matsuzawa, Yasushi; Konishi, Masaaki; Akiyama, Eiichi; Kurokawa, Hirofumi; Maeda, Hirofumi; Sugamura, Koichi; Nagayoshi, Yasuhiro; Morihisa, Kenji; Sakamoto, Kenji; Tsujita, Kenichi; Yamamoto, Eiichiro; Yamamuro, Megumi; Kojima, Sunao; Kaikita, Koichi; Tayama, Shinji; Hokimoto, Seiji; Matsui, Kunihiko; Sakamoto, Tomohiro; Ogawa, Hisao

    2012-10-01

    distinctive clinical features and endothelial dysfunction that are important to recognize as nonobstructive coronary artery disease so that optimal care with calcium channel blockers can be provided. URL: www.umin.ac.jp/ctr. Unique identifier: UMIN000003839.

  14. Identification of a phenotypically and functionally distinct population of long-lived neutrophils in a model of reverse endothelial migration.

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    Buckley, Christopher D; Ross, Ewan A; McGettrick, Helen M; Osborne, Chloe E; Haworth, Oliver; Schmutz, Caroline; Stone, Philip C W; Salmon, Mike; Matharu, Nick M; Vohra, Rajiv K; Nash, Gerard B; Rainger, G Ed

    2006-02-01

    Recent studies have demonstrated that neutrophils are not a homogenous population of cells. Here, we have identified a subset of human neutrophils with a distinct profile of cell-surface receptors [CD54(high), CXC chemokine receptor 1(low) (CXCR1(low))], which represent cells that have migrated through an endothelial monolayer and then re-emerged by reverse transmigration (RT). RT neutrophils, when in contact with endothelium, were rescued from apoptosis, demonstrate functional priming, and were rheologically distinct from neutrophils that had not undergone transendothelial migration. In vivo, 1-2% of peripheral blood neutrophils in patients with systemic inflammation exhibit a RT phenotype. A smaller population existed in healthy donors ( approximately 0.25%). RT neutrophils were distinct from naïve circulatory neutrophils (CD54(low), CXCR1(high)) and naïve cells after activation with formyl-Met-Leu-Phe (CD54(low), CXCR1(low)). It is important that the RT phenotype (CD54(high), CXCR1(low)) is also distinct from tissue-resident neutrophils (CD54(low), CXCR1(low)). Our results demonstrate that neutrophils can migrate in a retrograde direction across endothelial cells and suggest that a population of tissue-experienced neutrophils with a distinct phenotype and function are present in the peripheral circulation in humans in vivo.

  15. A truncation allele in vascular endothelial growth factor c reveals distinct modes of signaling during lymphatic and vascular development.

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    Villefranc, Jacques A; Nicoli, Stefania; Bentley, Katie; Jeltsch, Michael; Zarkada, Georgia; Moore, John C; Gerhardt, Holger; Alitalo, Kari; Lawson, Nathan D

    2013-04-01

    Vascular endothelial growth factor C (Vegfc) is a secreted protein that guides lymphatic development in vertebrate embryos. However, its role during developmental angiogenesis is not well characterized. Here, we identify a mutation in zebrafish vegfc that severely affects lymphatic development and leads to angiogenesis defects on sensitized genetic backgrounds. The um18 mutation prematurely truncated Vegfc, blocking its secretion and paracrine activity but not its ability to activate its receptor Flt4. When expressed in endothelial cells, vegfc(um18) could not rescue lymphatic defects in mutant embryos, but induced ectopic blood vessel branching. Furthermore, vegfc-deficient endothelial cells did not efficiently contribute to tip cell positions in developing sprouts. Computational modeling together with assessment of endothelial cell dynamics by time-lapse analysis suggested that an autocrine Vegfc/Flt4 loop plays an important role in migratory persistence and filopodia stability during sprouting. Our results suggest that Vegfc acts in two distinct modes during development: as a paracrine factor secreted from arteries to guide closely associated lymphatic vasculature and as an autocrine factor to drive migratory persistence during angiogenesis.

  16. Angiotensin II Evokes Angiogenic Signals within Skeletal Muscle through Co-ordinated Effects on Skeletal Myocytes and Endothelial Cells

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    Gorman, Jennifer L.; Liu, Sammy T. K.; Slopack, Dara; Shariati, Khashayar; Hasanee, Adam; Olenich, Sara; Olfert, I. Mark; Haas, Tara L.

    2014-01-01

    Skeletal muscle overload induces the expression of angiogenic factors such as vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-2, leading to new capillary growth. We found that the overload-induced increase in angiogenesis, as well as increases in VEGF, MMP-2 and MT1-MMP transcripts were abrogated in muscle VEGF KO mice, highlighting the critical role of myocyte-derived VEGF in controlling this process. The upstream mediators that contribute to overload-induced expression of VEGF have yet to be ascertained. We found that muscle overload increased angiotensinogen expression, a precursor of angiotensin (Ang) II, and that Ang II signaling played an important role in basal VEGF production in C2C12 cells. Furthermore, matrix-bound VEGF released from myoblasts induced the activation of endothelial cells, as evidenced by elevated endothelial cell phospho-p38 levels. We also found that exogenous Ang II elevates VEGF expression, as well as MMP-2 transcript levels in C2C12 myotubes. Interestingly, these responses also were observed in skeletal muscle endothelial cells in response to Ang II treatment, indicating that these cells also can respond directly to the stimulus. The involvement of Ang II in muscle overload-induced angiogenesis was assessed. We found that blockade of AT1R-dependent Ang II signaling using losartan did not attenuate capillary growth. Surprisingly, increased levels of VEGF protein were detected in overloaded muscle from losartan-treated rats. Similarly, we observed elevated VEGF production in cultured endothelial cells treated with losartan alone or in combination with Ang II. These studies conclusively establish the requirement for muscle derived VEGF in overload-induced angiogenesis and highlight a role for Ang II in basal VEGF production in skeletal muscle. However, while Ang II signaling is activated following overload and plays a role in muscle VEGF production, inhibition of this pathway is not sufficient to halt overload

  17. Influence of electrospun scaffolds prepared from distinct polymers on proliferation and viability of endothelial cells

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    Matveeva, V. G., E-mail: matveeva-vg@mail.ru; Antonova, L. V., E-mail: antonova.la@mail.ru; Velikanova, E. A.; Sergeeva, E. A.; Krivkina, E. O.; Glushkova, T. V.; Kudryavtseva, Yu. A.; Barbarash, O. L.; Barbarash, L. S. [Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo, 650002 (Russian Federation)

    2015-10-27

    We compared electrospun nonwoven scaffolds from polylactic acid (PLA), polycaprolactone (PCL), and polyhydroxybutyrate/valerate (PHBV)/polycaprolactone (PHBV/PCL). The surface of PHBV/PCL and PCL scaffolds was highly porous and consisted of randomly distributed fibers, whilst the surface of PLA scaffolds consisted of thin straight fibers, which located more sparsely, forming large pores. Culture of EA.hy 926 endothelial cells on these scaffolds during 7 days and further fluorescent microscopy demonstrated that the surface of PHBV/PCL scaffolds was most favorable for efficient adhesion, proliferation, and viability of endothelial cells. The lowest proliferation rate and cell viability were detected on PLA scaffolds. Therefore, PHBV/PCL electrospun nonwoven scaffolds demonstrated the best results regarding endothelial cell proliferation and viability as compared to PCL and PLA scaffolds.

  18. Morph or Move? How Distinct Endothelial Cell Responses to Blood Flow Shape Vascular Networks.

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    Franco, Claudio A; Gerhardt, Holger

    2017-06-19

    Blood vessel shape is malleable and dynamically regulated. In two recent papers in Nature Cell Biology, Jin et al. (2017) and Sugden et al. (2017) show that endoglin alters endothelial cell shape or behavior in response to blood flow, thus regulating vessel structure. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Distinct tissue formation by heterogeneous printing of osteo- and endothelial progenitor cells.

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    Fedorovich, Natalja E; Wijnberg, Hans M; Dhert, Wouter J A; Alblas, Jacqueline

    2011-08-01

    The organ- or tissue-printing approach, based on layered deposition of cell-laden hydrogels, is a new technique in regenerative medicine suitable to investigate whether mimicking the anatomical organization of cells, matrix, and bioactive molecules is necessary for obtaining or improving functional engineered tissues. Currently, data on performance of multicellular printed constructs in vivo are limited. In this study we illustrate the ability of the system to print intricate porous constructs containing two different cell types--endothelial progenitors and multipotent stromal cells--and show that these grafts retain heterogeneous cell organization after subcutaneous implantation in immunodeficient mice. We demonstrate that cell differentiation leading to the expected tissue formation occurs at the site of the deposited progenitor cell type. While perfused blood vessels are formed in the endothelial progenitor cell-laden part of the constructs, bone formation is taking place in the multipotent stromal cell-laden part of the printed grafts.

  20. Endothelial and Neuronal Nitric Oxide Activate Distinct Pathways on Sympathetic Neurotransmission in Rat Tail and Mesenteric Arteries.

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    Joana Beatriz Sousa

    Full Text Available Nitric oxide (NO seems to contribute to vascular homeostasis regulating neurotransmission. This work aimed at assessing the influence of NO from different sources and respective intracellular pathways on sympathetic neurotransmission, in two vascular beds. Electrically-evoked [3H]-noradrenaline release was assessed in rat mesenteric and tail arteries in the presence of NO donors or endothelial/neuronal nitric oxide synthase (NOS inhibitors. The influence of NO on adenosine-mediated effects was also studied using selective antagonists for adenosine receptors subtypes. Location of neuronal NOS (nNOS was investigated by immunohistochemistry (with specific antibodies for nNOS and for Schwann cells and Confocal Microscopy. Results indicated that: 1 in mesenteric arteries, noradrenaline release was reduced by NO donors and it was increased by nNOS inhibitors; the effect of NO donors was only abolished by the adenosine A1 receptors antagonist; 2 in tail arteries, noradrenaline release was increased by NO donors and it was reduced by eNOS inhibitors; adenosine receptors antagonists were devoid of effect; 3 confocal microscopy showed nNOS staining in adventitial cells, some co-localized with Schwann cells. nNOS staining and its co-localization with Schwann cells were significantly lower in tail compared to mesenteric arteries. In conclusion, in mesenteric arteries, nNOS, mainly located in Schwann cells, seems to be the main source of NO influencing perivascular sympathetic neurotransmission with an inhibitory effect, mediated by adenosine A1 receptors activation. Instead, in tail arteries endothelial NO seems to play a more relevant role and has a facilitatory effect, independent of adenosine receptors activation.

  1. The Medium is the Message: Pictures and Objects Evoke Distinct Conceptual Relations in Parent-Child Conversations

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    Ware, Elizabeth A.; Gelman, Susan A.; Kleinberg, Felicia

    2013-01-01

    An important developmental task is learning to organize experience by forming conceptual relations among entities (e.g., a lion and a snake can be linked because both are animals; a lion and a cage can be linked because the lion lives in the cage). We propose that representational medium (i.e., pictures vs. objects) plays an important role in influencing which relations children consider. Prior work has demonstrated that pictures more readily evoke broader categories, whereas objects more readily call attention to specific individuals. We therefore predicted that pictures would encourage taxonomic and shared-property relations, whereas objects would encourage thematic and slot-filler relations. We observed 32 mother-child dyads (M child ages = 2.9 and 4.3) playing with pictures and objects, and identified utterances in which they made taxonomic, thematic, shared-property, or slot-filler links between items. The results confirmed our predictions and thus support representational medium as an important factor that influences the conceptual relations expressed during dyadic conversations. PMID:24273367

  2. Distinct subcellular trafficking resulting from monomeric vs multimeric targeting to endothelial ICAM-1: implications for drug delivery.

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    Ghaffarian, Rasa; Muro, Silvia

    2014-12-01

    Ligand-targeted, receptor-mediated endocytosis is commonly exploited for intracellular drug delivery. However, cells-surface receptors may follow distinct endocytic fates when bound by monomeric vs multimeric ligands. Our purpose was to study this paradigm using ICAM-1, an endothelial receptor involved in inflammation, to better understand its regulation and potential for drug delivery. Our procedure involved fluorescence microscopy of human endothelial cells to determine the endocytic behavior of unbound ICAM-1 vs ICAM-1 bound by model ligands: monomeric (anti-ICAM) vs multimeric (anti-ICAM biotin-streptavidin conjugates or anti-ICAM coated onto 100 nm nanocarriers). Our findings suggest that both monomeric and multimeric ligands undergo a similar endocytic pathway sensitive to amiloride (∼50% inhibition), but not inhibitors of clathrin-pits or caveoli. After 30 min, ∼60-70% of both ligands colocalized with Rab11a-compartments. By 3-5 h, ∼65-80% of multimeric anti-ICAM colocalized with perinuclear lysosomes with ∼60-80% degradation, while 70% of monomeric anti-ICAM remained associated with Rab11a at the cell periphery and recycled to and from the cell-surface with minimal (<10%) lysosomal colocalization and minimal (≤15%) degradation. In the absence of ligands, ICAM-1 also underwent amiloride-sensitive endocytosis with peripheral distribution, suggesting that monomeric (not multimeric) anti-ICAM follows the route of this receptor. In conclusion, ICAM-1 can mediate different intracellular itineraries, revealing new insight into this biological pathway and alternative avenues for drug delivery.

  3. Stromal Interaction Molecule 1 (STIM1) and Orai1 Mediate Histamine-evoked Calcium Entry and Nuclear Factor of Activated T-cells (NFAT) Signaling in Human Umbilical Vein Endothelial Cells*

    Science.gov (United States)

    Zhou, Meng-Hua; Zheng, Hongying; Si, Hongjiang; Jin, Yixin; Peng, Jasmine M.; He, Lian; Zhou, Yubin; Muñoz-Garay, Carlos; Zawieja, David C.; Kuo, Lih; Peng, Xu; Zhang, Shenyuan L.

    2014-01-01

    Histamine is an important immunomodulator involved in allergic reactions and inflammatory responses. In endothelial cells, histamine induces Ca2+ mobilization by releasing Ca2+ from the endoplasmic reticulum and eliciting Ca2+ entry across the plasma membrane. Herein, we show that histamine-evoked Ca2+ entry in human umbilical vein endothelial cells (HUVECs) is sensitive to blockers of Ca2+ release-activated Ca2+ (CRAC) channels. RNA interference against STIM1 or Orai1, the activating subunit and the pore-forming subunit of CRAC channels, respectively, abolishes this histamine-evoked Ca2+ entry. Furthermore, overexpression of dominant-negative CRAC channel subunits inhibits while co-expression of both STIM1 and Orai1 enhances histamine-induced Ca2+ influx. Interestingly, gene silencing of STIM1 or Orai1 also interrupts the activation of calcineurin/nuclear factor of activated T-cells (NFAT) pathway and the production of interleukin 8 triggered by histamine in HUVECs. Collectively, these results suggest a central role of STIM1 and Orai1 in mediating Ca2+ mobilization linked to inflammatory signaling of endothelial cells upon histamine stimulation. PMID:25190815

  4. Distinct and overlapping roles of Nipah virus P gene products in modulating the human endothelial cell antiviral response.

    Directory of Open Access Journals (Sweden)

    Michael K Lo

    Full Text Available Nipah virus (NiV is a highly pathogenic zoonotic paramyxovirus that causes fatal encephalitis in up to 75% of infected humans. Like other paramyxoviruses, NiV employs co-transcriptional mRNA editing during transcription of the phosphoprotein (P gene to generate additional mRNAs encoding the V and W proteins. The C protein is translated from the P mRNA, but in an alternative reading frame. There is evidence from both in vitro and in vivo studies to show that the P gene products play a role in NiV pathogenesis. We have developed a reverse genetic system to dissect the individual roles of the NiV P gene products in limiting the antiviral response in primary human microvascular lung endothelial cells, which represent important targets in human NiV infection. By characterizing growth curves and early antiviral responses against a number of recombinant NiVs with genetic modifications altering expression of the proteins encoded by the P gene, we observed that multiple elements encoded by the P gene have both distinct and overlapping roles in modulating virus replication as well as in limiting expression of antiviral mediators such as IFN-β, CXCL10, and CCL5. Our findings corroborate observations from in vivo hamster infection studies, and provide molecular insights into the attenuation and the histopathology observed in hamsters infected with C, V, and W-deficient NiVs. The results of this study also provide an opportunity to verify the results of earlier artificial plasmid expression studies in the context of authentic viral infection.

  5. Distinct and overlapping roles of Nipah virus P gene products in modulating the human endothelial cell antiviral response.

    Science.gov (United States)

    Lo, Michael K; Peeples, Mark E; Bellini, William J; Nichol, Stuart T; Rota, Paul A; Spiropoulou, Christina F

    2012-01-01

    Nipah virus (NiV) is a highly pathogenic zoonotic paramyxovirus that causes fatal encephalitis in up to 75% of infected humans. Like other paramyxoviruses, NiV employs co-transcriptional mRNA editing during transcription of the phosphoprotein (P) gene to generate additional mRNAs encoding the V and W proteins. The C protein is translated from the P mRNA, but in an alternative reading frame. There is evidence from both in vitro and in vivo studies to show that the P gene products play a role in NiV pathogenesis. We have developed a reverse genetic system to dissect the individual roles of the NiV P gene products in limiting the antiviral response in primary human microvascular lung endothelial cells, which represent important targets in human NiV infection. By characterizing growth curves and early antiviral responses against a number of recombinant NiVs with genetic modifications altering expression of the proteins encoded by the P gene, we observed that multiple elements encoded by the P gene have both distinct and overlapping roles in modulating virus replication as well as in limiting expression of antiviral mediators such as IFN-β, CXCL10, and CCL5. Our findings corroborate observations from in vivo hamster infection studies, and provide molecular insights into the attenuation and the histopathology observed in hamsters infected with C, V, and W-deficient NiVs. The results of this study also provide an opportunity to verify the results of earlier artificial plasmid expression studies in the context of authentic viral infection.

  6. Characterization of a distinct population of circulating human non-adherent endothelial forming cells and their recruitment via intercellular adhesion molecule-3.

    Directory of Open Access Journals (Sweden)

    Sarah L Appleby

    Full Text Available Circulating vascular progenitor cells contribute to the pathological vasculogenesis of cancer whilst on the other hand offer much promise in therapeutic revascularization in post-occlusion intervention in cardiovascular disease. However, their characterization has been hampered by the many variables to produce them as well as their described phenotypic and functional heterogeneity. Herein we have isolated, enriched for and then characterized a human umbilical cord blood derived CD133(+ population of non-adherent endothelial forming cells (naEFCs which expressed the hematopoietic progenitor cell markers (CD133, CD34, CD117, CD90 and CD38 together with mature endothelial cell markers (VEGFR2, CD144 and CD31. These cells also expressed low levels of CD45 but did not express the lymphoid markers (CD3, CD4, CD8 or myeloid markers (CD11b and CD14 which distinguishes them from 'early' endothelial progenitor cells (EPCs. Functional studies demonstrated that these naEFCs (i bound Ulex europaeus lectin, (ii demonstrated acetylated-low density lipoprotein uptake, (iii increased vascular cell adhesion molecule (VCAM-1 surface expression in response to tumor necrosis factor and (iv in co-culture with mature endothelial cells increased the number of tubes, tubule branching and loops in a 3-dimensional in vitro matrix. More importantly, naEFCs placed in vivo generated new lumen containing vasculature lined by CD144 expressing human endothelial cells (ECs. Extensive genomic and proteomic analyses of the naEFCs showed that intercellular adhesion molecule (ICAM-3 is expressed on their cell surface but not on mature endothelial cells. Furthermore, functional analysis demonstrated that ICAM-3 mediated the rolling and adhesive events of the naEFCs under shear stress. We suggest that the distinct population of naEFCs identified and characterized here represents a new valuable therapeutic target to control aberrant vasculogenesis.

  7. Characterization of a Distinct Population of Circulating Human Non-Adherent Endothelial Forming Cells and Their Recruitment via Intercellular Adhesion Molecule-3

    Science.gov (United States)

    Thompson, Emma J.; Barrett, Jeffrey M.; Tooley, Katie; Sen, Shaundeep; Sun, Wai Yan; Grose, Randall; Nicholson, Ian; Levina, Vitalina; Cooke, Ira; Talbo, Gert; Lopez, Angel F.; Bonder, Claudine S.

    2012-01-01

    Circulating vascular progenitor cells contribute to the pathological vasculogenesis of cancer whilst on the other hand offer much promise in therapeutic revascularization in post-occlusion intervention in cardiovascular disease. However, their characterization has been hampered by the many variables to produce them as well as their described phenotypic and functional heterogeneity. Herein we have isolated, enriched for and then characterized a human umbilical cord blood derived CD133+ population of non-adherent endothelial forming cells (naEFCs) which expressed the hematopoietic progenitor cell markers (CD133, CD34, CD117, CD90 and CD38) together with mature endothelial cell markers (VEGFR2, CD144 and CD31). These cells also expressed low levels of CD45 but did not express the lymphoid markers (CD3, CD4, CD8) or myeloid markers (CD11b and CD14) which distinguishes them from ‘early’ endothelial progenitor cells (EPCs). Functional studies demonstrated that these naEFCs (i) bound Ulex europaeus lectin, (ii) demonstrated acetylated-low density lipoprotein uptake, (iii) increased vascular cell adhesion molecule (VCAM-1) surface expression in response to tumor necrosis factor and (iv) in co-culture with mature endothelial cells increased the number of tubes, tubule branching and loops in a 3-dimensional in vitro matrix. More importantly, naEFCs placed in vivo generated new lumen containing vasculature lined by CD144 expressing human endothelial cells (ECs). Extensive genomic and proteomic analyses of the naEFCs showed that intercellular adhesion molecule (ICAM)-3 is expressed on their cell surface but not on mature endothelial cells. Furthermore, functional analysis demonstrated that ICAM-3 mediated the rolling and adhesive events of the naEFCs under shear stress. We suggest that the distinct population of naEFCs identified and characterized here represents a new valuable therapeutic target to control aberrant vasculogenesis. PMID:23144795

  8. GPR182 is a novel marker for sinusoidal endothelial differentiation with distinct GPCR signaling activity in vitro.

    Science.gov (United States)

    Schmid, Christian David; Schledzewski, Kai; Mogler, Carolin; Waldburger, Nina; Kalna, Viktoria; Marx, Alexander; Randi, Anna Maria; Géraud, Cyrill; Goerdt, Sergij; Koch, Philipp-Sebastian

    2018-02-01

    Endothelial cells (EC) along the vascular tree exhibit organ-specific angiodiversity. Compared to most other ECs, liver sinusoidal endothelial cells (LSEC) that constitute the organ-specific microvasculature of the liver are morphologically and functionally unique. Previously, we showed that transcription factor Gata4 acts as a master regulator controlling LSEC differentiation. Upon analysis of the molecular signature of LSEC, we identified GPR182 as a potential LSEC-specific orphan G-protein coupled receptor (GPCR). Here, we demonstrate that GPR182 is expressed by LSEC and by EC with sinusoidal differentiation in spleen, lymph node and bone marrow in healthy human tissues. In a tissue microarray analysis of human hepatocellular carcinoma (HCC) samples, endothelial GPR182 expression was significantly reduced in tumor samples compared to peritumoral liver tissue samples (p = 0.0105). Loss of endothelial GPR182 expression was also seen in fibrotic and cirrhotic liver tissues. In vitro, GPR182 differentially regulated canonical GPCR signaling pathways as shown using reporter luciferase assays in HEK293T cells. Whereas ERK and RhoA signaling were inhibited, CREB and Calcium signaling were activated by ectopic GPR182 overexpression. Our data demonstrate that GPR182 is an endothelial subtype-specific marker for human sinusoidal EC of the liver, spleen, lymph node and bone marrow. In addition, we provide evidence for GPR182-dependent downstream signaling via ERK and SRF pathways that may be involved in regulating endothelial subtype-specific sinusoidal differentiation and sinusoidal functions such as permeability. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  9. Proprioceptive evoked gamma oscillations

    DEFF Research Database (Denmark)

    Arnfred, S.M.; Hansen, Lars Kai; Parnas, J.

    2007-01-01

    A proprioceptive stimulus consisting of a weight change of a handheld load has recently been shown to elicit an evoked potential. Previously, somatosensory gamma oscillations have only been evoked by electrical stimuli. We conjectured that a natural proprioceptive stimulus also would be able...... to evoke gamma oscillations. EEG was recorded using 64 channels in 14 healthy subjects. In each of three runs a stimulus of 100 g load increment in each hand was presented in 120 trials. Data were wavelet transformed and runs collapsed. Inter-trial phase coherence (ITPC) was computed as the best measure...... contralateral to stimulus side and additionally an unexpected 20 Hz activity was observed slightly lateralized in the frontal central region. The gamma phase locking may be a manifestation of early somatosensory feature integration. The analyses suggest that the high frequency activity consists of two distinct...

  10. Distinctive expression patterns of hypoxia-inducible factor-1α and endothelial nitric oxide synthase following hypergravity exposure.

    Science.gov (United States)

    Yoon, Gun; Oh, Choong Sik; Kim, Hyun-Soo

    2016-06-07

    This study was designed to examine the expression of hypoxia-inducible factor-1α (HIF-1α) and the level and activity of endothelial nitric oxide synthase (eNOS) in the hearts and livers of mice exposed to hypergravity. Hypergravity-induced hypoxia and the subsequent post-exposure reoxygenation significantly increased cardiac HIF-1α levels. Furthermore, the levels and activity of cardiac eNOS also showed significant increase immediately following hypergravity exposure and during the reoxygenation period. In contrast, the expression of phosphorylated Akt (p-Akt) and phosphorylated extracellular signal-regulated kinase (p-ERK) showed significant elevation only during the reoxygenation period. These data raise the possibility that the increase in cardiac HIF-1α expression induced by reoxygenation involves a cascade of signaling events, including activation of the Akt and ERK pathways. In the liver, HIF-1α expression was significantly increased immediately after hypergravity exposure, indicating that hypergravity exposure to causes hepatocellular hypoxia. The hypergravity-exposed livers showed significantly higher eNOS immunoreactivity than did those of control mice. Consistent with these results, significant increases in eNOS activity and nitrate/nitrite levels were also observed. These findings suggest that hypergravity-induced hypoxia plays a significant role in the upregulation of hepatic eNOS.

  11. Distinction of neurons, glia and endothelial cells in the cerebral cortex: an algorithm based on cytological features

    Directory of Open Access Journals (Sweden)

    Miguel Ángel García-Cabezas

    2016-11-01

    Full Text Available The estimation of the number or density of neurons and types of glial cells and their relative proportions in different brain areas are at the core of rigorous quantitative neuroanatomical studies. Unfortunately, the lack of detailed, updated, systematic, and well-illustrated descriptions of the cytology of neurons and glial cell types, especially in the primate brain, makes such studies especially demanding, often limiting their scope and broad use. Here, following extensive analysis of histological materials and the review of current and classical literature, we compile a list of precise morphological criteria that can facilitate and standardize identification of cells in stained sections examined under the microscope. We describe systematically and in detail the cytological features of neurons and glial cell types in the cerebral cortex of the macaque monkey and the human using semithin and thick sections stained for Nissl. We used this classical staining technique because it labels all cells in the brain in distinct ways. In addition, we corroborate key distinguishing characteristics of different cell types in sections immunolabeled for specific markers counterstained for Nissl and in ultrathin sections processed for electron microscopy. Finally, we summarize the core features that distinguish each cell type in easy-to-use tables and sketches, and structure these key features in an algorithm that can be used to systematically distinguish cellular types in the cerebral cortex. Moreover, we report high inter-observer algorithm reliability, which is a crucial test for obtaining consistent and reproducible cell counts in unbiased stereological studies. This protocol establishes a consistent framework that can be used to reliably identify and quantify cells in the cerebral cortex of primates as well as other mammalian species in health and disease.

  12. In inflammatory reactive astrocytes co-cultured with brain endothelial cells nicotine-evoked Ca(2+) transients are attenuated due to interleukin-1beta release and rearrangement of actin filaments.

    Science.gov (United States)

    Delbro, D; Westerlund, A; Björklund, U; Hansson, E

    2009-03-17

    The aim of this study was to investigate whether nicotine acetylcholine receptors (nAChRs) are expressed in a more pronounced way in astrocytes co-cultured with microvascular endothelial cells from adult rat brain, compared with monocultured astrocytes, as a sign of a more developed signal transduction system. Also investigated was whether nicotine plays a role in the control of neuroinflammatory reactivity in astrocytes. Ca(2+) imaging experiments were performed using cells loaded with the Ca(2+) indicator Fura-2/AM. Co-cultured astrocytes responded to lower concentrations of nicotine than did monocultured astrocytes, indicating that they are more sensitive to nicotine. Co-cultured astrocytes also expressed a higher selectivity for alpha7nAChR and alpha4/beta2 subunits and evoked higher Ca(2+) transients compared with monocultured astrocytes. The Ca(2+) transients referred to are activators of Ca(2+)-induced Ca(2+) release from intracellular stores, both IP(3) and ryanodine, triggered by influx through receptor channels. The nicotine-induced Ca(2+) transients were attenuated after incubation with the inflammatory mediator lipopolysaccharide (LPS), but were not attenuated after incubation with the pain-transmitting peptides substance P and calcitonin-gene-related peptide, nor with the infection and inflammation stress mediator, leptin. Furthermore, LPS-induced release of interleukin-1beta (IL-1beta) measured by enzyme-linked immunosorbent assay (ELISA) was more pronounced in co-cultured versus monocultured astrocytes. Incubation with both LPS and IL-1beta further attenuated nicotine-induced Ca(2+) response. We also found that LPS and IL-1beta induced rearrangement of the F-actin filaments, as measured with an Alexa488-conjugated phalloidin probe. The rearrangements consisted of increases in ring formations and a more dispersed appearance of the filaments. These results indicate that there is a connection between a dysfunction of nicotine Ca(2+) signaling in

  13. In Vitro Endothelial Cell Proliferation Assay Reveals Distinct Levels of Proangiogenic Cytokines Characterizing Sera of Healthy Subjects and of Patients with Heart Failure

    Directory of Open Access Journals (Sweden)

    Rebecca Voltan

    2014-01-01

    Full Text Available Although myocardial angiogenesis is thought to play an important role in heart failure (HF, the involvement of circulating proinflammatory and proangiogenic cytokines in the pathogenesis and/or prognosis of HF has not been deeply investigated. By using a highly standardized proliferation assay with human endothelial cells, we first demonstrated that sera from older (mean age 52±7.6 years; n=46 healthy donors promoted endothelial cell proliferation to a significantly higher extent compared to sera obtained from younger healthy donors (mean age 29±8.6 years; n=20. The promotion of endothelial cell proliferation was accompanied by high serum levels of several proangiogenic cytokines. When we assessed endothelial cell proliferation in response to HF patients’ sera, we observed that a subset of sera (n=11 promoted cell proliferation to a significantly lesser extent compared to the majority of sera (n=18. Also, in this case, the difference between the patient groups in the ability to induce endothelial cell proliferation correlated to significant (P<0.05 differences in serum proangiogenic cytokine levels. Unexpectedly, HF patients associated to the highest endothelial proliferation index showed the worst prognosis as evaluated in terms of subsequent cardiovascular events in the follow-up, suggesting that high levels of circulating proangiogenic cytokines might be related to a worse prognosis.

  14. Rosetting Plasmodium falciparum-infected erythrocytes bind to human brain microvascular endothelial cells in vitro, demonstrating a dual adhesion phenotype mediated by distinct P. falciparum erythrocyte membrane protein 1 domains.

    Science.gov (United States)

    Adams, Yvonne; Kuhnrae, Pongsak; Higgins, Matthew K; Ghumra, Ashfaq; Rowe, J Alexandra

    2014-03-01

    Adhesion interactions between Plasmodium falciparum-infected erythrocytes (IE) and human cells underlie the pathology of severe malaria. IE cytoadhere to microvascular endothelium or form rosettes with uninfected erythrocytes to survive in vivo by sequestering IE in the microvasculature and avoiding splenic clearance mechanisms. Both rosetting and cytoadherence are mediated by the parasite-derived IE surface protein family Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1). Rosetting and cytoadherence have been widely studied as separate entities; however, the ability of rosetting P. falciparum strains to cytoadhere has received little attention. Here, we show that IE of the IT/R29 strain expressing a rosette-mediating PfEMP1 variant (IT4var09) cytoadhere in vitro to a human brain microvascular endothelial cell line (HBEC-5i). Cytoadherence was inhibited by heparin and by treatment of HBEC-5i with heparinase III, suggesting that the endothelial receptors for IE binding are heparan sulfate proteoglycans. Antibodies to the N-terminal regions of the IT4var09 PfEMP1 variant (NTS-DBL1α and DBL2γ domains) specifically inhibited and reversed cytoadherence down to low concentrations (experiments showed that the NTS-DBLα and DBL2γ domains bind strongly to heparin, with half-maximal binding at a concentration of ∼0.5 μM in both cases. Therefore, cytoadherence of IT/R29 IE is distinct from rosetting, which is primarily mediated by NTS-DBL1α interactions with complement receptor 1. These data show that IT4var09-expressing parasites are capable of dual interactions with both endothelial cells and uninfected erythrocytes via distinct receptor-ligand interactions.

  15. Endothelial neuropilin disruption in mice causes DiGeorge syndrome-like malformations via mechanisms distinct to those caused by loss of Tbx1.

    Directory of Open Access Journals (Sweden)

    Jingjing Zhou

    Full Text Available The spectrum of human congenital malformations known as DiGeorge syndrome (DGS is replicated in mice by mutation of Tbx1. Vegfa has been proposed as a modifier of DGS, based in part on the occurrence of comparable phenotypes in Tbx1 and Vegfa mutant mice. Many additional genes have been shown to cause DGS-like phenotypes in mice when mutated; these generally intersect in some manner with Tbx1, and therefore impact the same developmental processes in which Tbx1 itself is involved. In this study, using Tie2Cre, we show that endothelial-specific mutation of the gene encoding the VEGFA coreceptor neuropilin-1 (Nrp1 also replicates the most prominent terminal phenotypes that typify DGS. However, the developmental etiologies of these defects are fundamentally different from those caused by absence of TBX1. In Tie2Cre/Nrp1 mutants, initial pharyngeal organization is normal but subsequent pharyngeal organ growth is impaired, second heart field differentiation is normal but cardiac outflow tract cushion organization is distorted, neural crest cell migration is normal, and palatal mesenchyme proliferation is impaired with no change in apoptosis. Our results demonstrate that impairment of VEGF-dependent endothelial pathways leads to a spectrum of DiGeorge syndrome-type malformations, through processes that are distinguishable from those controlled by Tbx1.

  16. Tyrosine kinase inhibitors directed against the vascular endothelial growth factor receptor (VEGFR) have distinct cutaneous toxicity profiles: a meta-analysis and review of the literature.

    Science.gov (United States)

    Massey, Paul R; Okman, Jonathan S; Wilkerson, Julia; Cowen, Edward W

    2015-06-01

    Inhibition of the vascular endothelial growth factor receptor (VEGFR) with tyrosine kinase inhibitors (TKIs) is associated with cutaneous adverse effects that increase patient morbidity. Our objective was to examine the skin toxicity profile of anti-VEGFR TKIs and determine the changing incidence in clinical trials. PubMed was queried for phase II or III trials of anti-VEGFR TKIs between 2000 and 2013 involving ≥50 patients. Adverse events were abstracted, with results presented in both fixed and random effects models. Odds ratios (OR) and 95 % confidence intervals (CIs) were estimated for studies with at least two arms. Across 82 included studies, all grades rash (OR, 2.68; 95 % CI, 2.45-2.94), hand-foot skin reaction (HFSR) (OR, 2.70; 95 % CI, 2.43-3.00), and pruritus (OR, 1.25; 95 % CI, 1.12-1.39) were associated with anti-VEGFR TKIs. Vandetanib had the highest incidence of rash (41 %), while sorafenib was most commonly associated with HFSR (37 %) and pruritus (14 %). The incidence of HFSR from 2000 to 2013 showed an upward trend (r (2) = 0.042, p = 0.10) and in sunitinib therapy increased significantly (r (2) = 0.237, p = 0.04). The incidence of HFSR, rash, and pruritus varies considerably by drug. Our data suggest a continued need to address skin toxicities and improve reporting strategies.

  17. Evoked cavernous activity.

    Science.gov (United States)

    Yilmaz, Uğur; Soylu, Ahmet; Ozcan, Cemal; Kutlu, Ramazan; Güneş, Ali

    2002-01-01

    Corpus cavernosum electromyography has been widely done to evaluate autonomic dysfunction in patients with erectile dysfunction. We assessed the value of corpus cavernosum electromyography, evoked cavernous activity and penile sympathetic skin responses for their accuracy in determining autonomic involvement in cases of erectile dysfunction. We evaluated 75 men with erectile dysfunction by corpus cavernosum electromyography, evoked cavernous activity and penile sympathetic skin response tests at our neurourology laboratory. The etiology of dysfunction was vascular, neurogenic, psychogenic or mixed based on a detailed medical and sexual history, physical examination, electrophysiological and laboratory studies, penile color Doppler ultrasonography, and cavernosography and/or cavernosometry. Autonomic involvement was clinically assessed by systemic findings, such as orthostatic hypotension, impaired gastrointestinal motility, sinus dysrhythmia and secretomotor changes. A concentric electromyography needle placed in the right cavernous body was used to record corpus cavernosum electromyography and evoked cavernous activity. The right median nerve was stimulated electrically with 13 to 16 mA. to determine evoked cavernous activity and the penile sympathetic skin response. The latter response was recorded with silver disc electrodes placed on the left cavernous body. All tests were performed using an electromyography/evoked potential machine. We determined the relationships among corpus cavernosum electromyography, evoked cavernous activity and penile sympathetic skin response tests in respect to etiological factors. The 56 patients with normal corpus cavernosum electromyography activity had also evoked cavernous activity and a penile sympathetic skin response except for 1 with no penile sympathetic skin response but evoked cavernous activity. None of these patients had autonomic neuropathy. Of the 19 patients without corpus cavernosum electromyography activity 11 had

  18. Evoked acoustic emission

    DEFF Research Database (Denmark)

    Elberling, C; Parbo, J; Johnsen, N J

    1985-01-01

    Stimulated acoustic emissions were recorded in response to tonal stimuli at 60 dB p.e. SPL in a small group of normal-hearing adults. Power spectral analysis reveals that the evoked activity from each ear contains energy in preferential frequency bands and the change of stimulus frequency has only...

  19. Proprioceptive evoked gamma oscillations

    DEFF Research Database (Denmark)

    Arnfred, Sidse M; Hansen, Lars Kai; Parnas, Josef

    2007-01-01

    to evoke gamma oscillations. EEG was recorded using 64 channels in 14 healthy subjects. In each of three runs a stimulus of 100 g load increment in each hand was presented in 120 trials. Data were wavelet transformed and runs collapsed. Inter-trial phase coherence (ITPC) was computed as the best measure...

  20. BAER - brainstem auditory evoked response

    Science.gov (United States)

    ... auditory potentials; Brainstem auditory evoked potentials; Evoked response audiometry; Auditory brainstem response; ABR; BAEP ... Normal results vary. Results will depend on the person and the instruments used to perform the test.

  1. Selecting and evoking innovators

    DEFF Research Database (Denmark)

    Kanstrup, Anne Marie; Christiansen, Ellen

    2006-01-01

    prepared for and conducted selection of and collaboration with innovators. The outcome was successful in the sense that the innovators produced excellent foundation for conceptual interaction design by creating mock-ups and explanations incarnating their preferences, attitudes and habits. By referring...... to theories of learning we try to explain how our way of working with selection and evoking of innovators has contributed to this positive result and how our approach to user-driven innovation can be regarded as a way to combine democracy and creativity in design....

  2. International Evoked Potentials Symposium

    CERN Document Server

    1980-01-01

    The past decade has seen great progress in the measurement of evoked potentials in man; a steady increase in our understanding of their charac­ teristics, their origins and their usefulness; and a growing application in the field of clinical diagnosis. The topic is a truly multidisciplinary one. Important research contributions have been made by workers of many different backgrounds and clinical applications span the specialities. This book represents a revised and updated version of the work originally presented at the international evoked potential symposium held in Nottingham 4-6 1978. The Nottingham Symposium provided a forum for a state-of-the-art discussion amongst workers from many different disciplines and from many different countries. For each major topic in the field an expert review set the scene for discussion of current research presentations. This format is retained in the book: the chapters in Part A provide the context in which the research presented in Part B is set. The task of selecting m...

  3. Vestibular evoked myogenic potential

    Directory of Open Access Journals (Sweden)

    Felipe, Lilian

    2012-01-01

    Full Text Available Introduction: The Vestibular Evoked Myogenic Potential (VEMP is a promising test for the evaluation of the cholic descending vestibular system. This reflex depends of the integrity from the saccular macula, from the inferior vestibular nerve, the vestibular nuclei, the vestibule-spinal tract and effectors muscles. Objective: Perform a systematic review of the pertinent literature by means of database (COCHRANE, MEDLINE, LILACS, CAPES. Conclusion: The clinical application of the VEMP has expanded in the last years, as goal that this exam is used as complementary in the otoneurological evaluation currently used. But, methodological issues must be clarified. This way, this method when combined with the standard protocol, can provide a more widely evaluation from the vestibular system. The standardization of the methodology is fundamental criterion for the replicability and sensibility of the exam.

  4. Music evokes vivid autobiographical memories.

    Science.gov (United States)

    Belfi, Amy M; Karlan, Brett; Tranel, Daniel

    2016-08-01

    Music is strongly intertwined with memories-for example, hearing a song from the past can transport you back in time, triggering the sights, sounds, and feelings of a specific event. This association between music and vivid autobiographical memory is intuitively apparent, but the idea that music is intimately tied with memories, seemingly more so than other potent memory cues (e.g., familiar faces), has not been empirically tested. Here, we compared memories evoked by music to those evoked by famous faces, predicting that music-evoked autobiographical memories (MEAMs) would be more vivid. Participants listened to 30 songs, viewed 30 faces, and reported on memories that were evoked. Memories were transcribed and coded for vividness as in Levine, B., Svoboda, E., Hay, J. F., Winocur, G., & Moscovitch, M. [2002. Aging and autobiographical memory: Dissociating episodic from semantic retrieval. Psychology and Aging, 17, 677-689]. In support of our hypothesis, MEAMs were more vivid than autobiographical memories evoked by faces. MEAMs contained a greater proportion of internal details and a greater number of perceptual details, while face-evoked memories contained a greater number of external details. Additionally, we identified sex differences in memory vividness: for both stimulus categories, women retrieved more vivid memories than men. The results show that music not only effectively evokes autobiographical memories, but that these memories are more vivid than those evoked by famous faces.

  5. Adjective metaphors evoke negative meanings.

    Science.gov (United States)

    Sakamoto, Maki; Utsumi, Akira

    2014-01-01

    Previous metaphor studies have paid much attention to nominal metaphors and predicative metaphors, but little attention has been given to adjective metaphors. Although some studies have focused on adjective metaphors, they only examined differences in the acceptability of various types of adjective metaphors. This paper explores the cognitive effects evoked by adjective metaphors. Three psychological experiments revealed that (1) adjective metaphors, especially those modified by color adjectives, tend to evoke negative effect; (2) although the meanings of metaphors are basically affected by the meanings of their vehicles, when a vehicle has a neutral meaning, negative meanings are evoked most frequently for adjective metaphors compared to nominal and predicative metaphors; (3) negative meanings evoked by adjective metaphors are related to poeticness, and poetic metaphors evoke negative meanings more easily than less poetic metaphors. Our research sheds new light on studies of the use of metaphor, which is one of the most basic human cognitive abilities.

  6. Adjective metaphors evoke negative meanings.

    Directory of Open Access Journals (Sweden)

    Maki Sakamoto

    Full Text Available Previous metaphor studies have paid much attention to nominal metaphors and predicative metaphors, but little attention has been given to adjective metaphors. Although some studies have focused on adjective metaphors, they only examined differences in the acceptability of various types of adjective metaphors. This paper explores the cognitive effects evoked by adjective metaphors. Three psychological experiments revealed that (1 adjective metaphors, especially those modified by color adjectives, tend to evoke negative effect; (2 although the meanings of metaphors are basically affected by the meanings of their vehicles, when a vehicle has a neutral meaning, negative meanings are evoked most frequently for adjective metaphors compared to nominal and predicative metaphors; (3 negative meanings evoked by adjective metaphors are related to poeticness, and poetic metaphors evoke negative meanings more easily than less poetic metaphors. Our research sheds new light on studies of the use of metaphor, which is one of the most basic human cognitive abilities.

  7. Human auditory evoked potentials. II - Effects of attention

    Science.gov (United States)

    Picton, T. W.; Hillyard, S. A.

    1974-01-01

    Attention directed toward auditory stimuli, in order to detect an occasional fainter 'signal' stimulus, caused a substantial increase in the N1 (83 msec) and P2 (161 msec) components of the auditory evoked potential without any change in preceding components. This evidence shows that human auditory attention is not mediated by a peripheral gating mechanism. The evoked response to the detected signal stimulus also contained a large P3 (450 msec) wave that was topographically distinct from the preceding components. This late positive wave could also be recorded in response to a detected omitted stimulus in a regular train and therefore seemed to index a stimulus-independent perceptual decision process.

  8. Distinctive effects of CD34- and CD133-specific antibody-coated stents on re-endothelialization and in-stent restenosis at the early phase of vascular injury

    DEFF Research Database (Denmark)

    Wu, Xue; Yin, Tieying; Tian, Jie

    2015-01-01

    It is not clear what effects of CD34- and CD133-specific antibody-coated stents have on re-endothelialization and in-stent restenosis (ISR) at the early phase of vascular injury. This study aims at determining the capabilities of different coatings on stents (e.g. gelatin, anti-CD133 and anti-CD34...... experiment using a rabbit model in which the coated stents with different substrates were implanted showed that anti-CD34 and anti-CD133 antibody-coated stents markedly reduced the intima area and restenosis than bare mental stents (BMS) and gelatin-coated stents. Compared with the anti-CD34 antibody...... for capturing EPCs is better than anti-CD34 antibody in promoting endothelialization and reducing ISR....

  9. L450W and Q455K Col8a2 knock-in mouse models of Fuchs endothelial corneal dystrophy show distinct phenotypes and evidence for altered autophagy.

    Science.gov (United States)

    Meng, Huan; Matthaei, Mario; Ramanan, Narendrakumar; Grebe, Rhonda; Chakravarti, Shukti; Speck, Caroline L; Kimos, Martha; Vij, Neeraj; Eberhart, Charles G; Jun, Albert S

    2013-03-28

    We compared the cellular phenotypes and studied the role of autophagy in the pathogenesis of Fuchs endothelial corneal dystrophy (FECD) using two α2 collagen VIII (Col8a2) knock-in mouse models and human FECD tissues. In vivo corneal endothelial cell (CEC) counts and morphology were analyzed by clinical confocal microscopy. Ultrastructural analysis of CECs was performed by transmission electron microscopy. Real-time PCR and Western blotting were performed using total RNA, and protein extracted from mouse CECs and human CECs obtained from FECD and autopsy patients. Both Col8a2 mouse models exhibited hallmarks of FECD; however, the Col8a2(L450W/L450W) mice exhibited a milder phenotype compared to the Col8a2(Q455K/Q455K) mice. Both models exhibited upregulation of the unfolded protein response (UPR) as evidenced by dilated rough endoplasmic reticulum (RER), and upregulation of UPR-associated genes and proteins. Real-time PCR of Col8a2(L450W/L450W) and Col8a2(Q455K/Q455K) CECs at 40 weeks revealed a 2.1-fold (P human FECD endothelium revealed a 10.4-fold upregulation of DRAM1 (P human FECD endothelial cells suggested a role for altered autophagy in this disease.

  10. Evoked emotions predict food choice.

    Directory of Open Access Journals (Sweden)

    Jelle R Dalenberg

    Full Text Available In the current study we show that non-verbal food-evoked emotion scores significantly improve food choice prediction over merely liking scores. Previous research has shown that liking measures correlate with choice. However, liking is no strong predictor for food choice in real life environments. Therefore, the focus within recent studies shifted towards using emotion-profiling methods that successfully can discriminate between products that are equally liked. However, it is unclear how well scores from emotion-profiling methods predict actual food choice and/or consumption. To test this, we proposed to decompose emotion scores into valence and arousal scores using Principal Component Analysis (PCA and apply Multinomial Logit Models (MLM to estimate food choice using liking, valence, and arousal as possible predictors. For this analysis, we used an existing data set comprised of liking and food-evoked emotions scores from 123 participants, who rated 7 unlabeled breakfast drinks. Liking scores were measured using a 100-mm visual analogue scale, while food-evoked emotions were measured using 2 existing emotion-profiling methods: a verbal and a non-verbal method (EsSense Profile and PrEmo, respectively. After 7 days, participants were asked to choose 1 breakfast drink from the experiment to consume during breakfast in a simulated restaurant environment. Cross validation showed that we were able to correctly predict individualized food choice (1 out of 7 products for over 50% of the participants. This number increased to nearly 80% when looking at the top 2 candidates. Model comparisons showed that evoked emotions better predict food choice than perceived liking alone. However, the strongest predictive strength was achieved by the combination of evoked emotions and liking. Furthermore we showed that non-verbal food-evoked emotion scores more accurately predict food choice than verbal food-evoked emotions scores.

  11. Evoked emotions predict food choice.

    Science.gov (United States)

    Dalenberg, Jelle R; Gutjar, Swetlana; Ter Horst, Gert J; de Graaf, Kees; Renken, Remco J; Jager, Gerry

    2014-01-01

    In the current study we show that non-verbal food-evoked emotion scores significantly improve food choice prediction over merely liking scores. Previous research has shown that liking measures correlate with choice. However, liking is no strong predictor for food choice in real life environments. Therefore, the focus within recent studies shifted towards using emotion-profiling methods that successfully can discriminate between products that are equally liked. However, it is unclear how well scores from emotion-profiling methods predict actual food choice and/or consumption. To test this, we proposed to decompose emotion scores into valence and arousal scores using Principal Component Analysis (PCA) and apply Multinomial Logit Models (MLM) to estimate food choice using liking, valence, and arousal as possible predictors. For this analysis, we used an existing data set comprised of liking and food-evoked emotions scores from 123 participants, who rated 7 unlabeled breakfast drinks. Liking scores were measured using a 100-mm visual analogue scale, while food-evoked emotions were measured using 2 existing emotion-profiling methods: a verbal and a non-verbal method (EsSense Profile and PrEmo, respectively). After 7 days, participants were asked to choose 1 breakfast drink from the experiment to consume during breakfast in a simulated restaurant environment. Cross validation showed that we were able to correctly predict individualized food choice (1 out of 7 products) for over 50% of the participants. This number increased to nearly 80% when looking at the top 2 candidates. Model comparisons showed that evoked emotions better predict food choice than perceived liking alone. However, the strongest predictive strength was achieved by the combination of evoked emotions and liking. Furthermore we showed that non-verbal food-evoked emotion scores more accurately predict food choice than verbal food-evoked emotions scores.

  12. Evoked Emotions Predict Food Choice

    NARCIS (Netherlands)

    Dalenberg, Jelle R.; Gutjar, Swetlana; ter Horst, Gert J.; de Graaf, Kees; Renken, Remco J.; Jager, Gerry

    2014-01-01

    In the current study we show that non-verbal food-evoked emotion scores significantly improve food choice prediction over merely liking scores. Previous research has shown that liking measures correlate with choice. However, liking is no strong predictor for food choice in real life environments.

  13. Recursive Distinctioning

    CERN Document Server

    Isaacson, Joel

    2016-01-01

    Recursive distinctioning (RD) is a name coined by Joel Isaacson in his original patent document describing how fundamental patterns of process arise from the systematic application of operations of distinction and description upon themselves. Recursive distinctioning means just what it says. A pattern of distinctions is given in a space based on a graphical structure (such as a line of print or a planar lattice or given graph). Each node of the graph is occupied by a letter from some arbitrary alphabet. A specialized alphabet is given that can indicate distinctions about neighbors of a given node. The neighbors of a node are all nodes that are connected to the given node by edges in the graph. The letters in the specialized alphabet (call it SA) are used to describe the states of the letters in the given graph and at each stage in the recursion, letters in SA are written at all nodes in the graph, describing its previous state. The recursive structure that results from the iteration of descriptions is called ...

  14. Evoked Emotions Predict Food Choice

    OpenAIRE

    Dalenberg, Jelle R.; Swetlana Gutjar; Gert J Ter Horst; Kees de Graaf; Renken, Remco J.; Gerry Jager

    2014-01-01

    In the current study we show that non-verbal food-evoked emotion scores significantly improve food choice prediction over merely liking scores. Previous research has shown that liking measures correlate with choice. However, liking is no strong predictor for food choice in real life environments. Therefore, the focus within recent studies shifted towards using emotion-profiling methods that successfully can discriminate between products that are equally liked. However, it is unclear how well ...

  15. EVOKED CAVERNOUS ACTIVITY: NEUROANATOMIC IMPLICATIONS

    OpenAIRE

    Yilmaz, Ugur; Vicars, Brenda; Yang, Claire C.

    2009-01-01

    We investigated the autonomic innervation of the penis by using evoked cavernous activity (ECA). We recruited 7 males with thoracic spinal cord injury (SCI) and sexual dysfunction and 6 males who were scheduled to have pelvic surgery (PS), specifically non-nerve-sparing radical cystoprostatectomy. In the PS subjects, ECA was performed both pre- and postoperatively. The left median nerve was electrically stimulated and ECA was recorded with two concentric electromyography needles placed into t...

  16. NLP-12 engages different UNC-13 proteins to potentiate tonic and evoked release.

    Science.gov (United States)

    Hu, Zhitao; Vashlishan-Murray, Amy B; Kaplan, Joshua M

    2015-01-21

    A neuropeptide (NLP-12) and its receptor (CKR-2) potentiate tonic and evoked ACh release at Caenorhabditis elegans neuromuscular junctions. Increased evoked release is mediated by a presynaptic pathway (egl-30 Gαq and egl-8 PLCβ) that produces DAG, and by DAG binding to short and long UNC-13 proteins. Potentiation of tonic ACh release persists in mutants deficient for egl-30 Gαq and egl-8 PLCβ and requires DAG binding to UNC-13L (but not UNC-13S). Thus, NLP-12 adjusts tonic and evoked release by distinct mechanisms. Copyright © 2015 the authors 0270-6474/15/351038-05$15.00/0.

  17. Model of evoked rabbit phonation.

    Science.gov (United States)

    Ge, Ping Jiang; French, Lesley C; Ohno, Tsunehisa; Zealear, David L; Rousseau, Bernard

    2009-01-01

    We describe a method for eliciting phonation in an in vivo rabbit preparation using low-frequency, bipolar pulsed stimulation of the cricothyroid muscles with airflow delivered to the glottis. Ten New Zealand White breeder rabbits weighing 3 to 5 kg were used in this study. The cricothyroid muscles were isolated bilaterally, and separate pairs of anode-cathode hooked-wire electrodes were inserted into each muscle. A Grass S-88 stimulator and 2 constant-current PSIU6 isolation units were used to deliver bipolar square wave pulses to each cricothyroid muscle, with airflow delivered to the glottis through a cuffed endotracheal tube. Phonation was evoked with a 50-Hz, 4-mA stimulus train of 1-ms pulses delivered to each cricothyroid muscle. The pulse trains were on for 2 seconds and were repeated every 5 seconds over a period of 180 minutes. Airflow was delivered at 143 cm3/s, producing phonation measuring 71 to 85 dB sound pressure level. Evoked phonation is feasible in rabbits by use of bipolar stimulation of the cricothyroid muscles with airflow delivered to the glottis. The in vivo rabbit preparation described may provide a useful small animal option for studies of evoked phonation. From the level and consistency of the adduction observed, we hypothesize that current spreading to the underlying adductor muscles and nerves resulted in neural pathway involvement beyond discrete activation of the cricothyroid muscle, providing sufficient approximation of the vocal folds for phonation.

  18. Contact heat evoked potentials using simultaneous EEG and fMRI and their correlation with evoked pain

    Directory of Open Access Journals (Sweden)

    Atherton Duncan

    2008-12-01

    Full Text Available Abstract Background The Contact Heat Evoked Potential Stimulator (CHEPS utilises rapidly delivered heat pulses with adjustable peak temperatures to stimulate the differential warm/heat thresholds of receptors expressed by Aδ and C fibres. The resulting evoked potentials can be recorded and measured, providing a useful clinical tool for the study of thermal and nociceptive pathways. Concurrent recording of contact heat evoked potentials using electroencephalogram (EEG and functional magnetic resonance imaging (fMRI has not previously been reported with CHEPS. Developing simultaneous EEG and fMRI with CHEPS is highly desirable, as it provides an opportunity to exploit the high temporal resolution of EEG and the high spatial resolution of fMRI to study the reaction of the human brain to thermal and nociceptive stimuli. Methods In this study we have recorded evoked potentials stimulated by 51°C contact heat pulses from CHEPS using EEG, under normal conditions (baseline, and during continuous and simultaneous acquisition of fMRI images in ten healthy volunteers, during two sessions. The pain evoked by CHEPS was recorded on a Visual Analogue Scale (VAS. Results Analysis of EEG data revealed that the latencies and amplitudes of evoked potentials recorded during continuous fMRI did not differ significantly from baseline recordings. fMRI results were consistent with previous thermal pain studies, and showed Blood Oxygen Level Dependent (BOLD changes in the insula, post-central gyrus, supplementary motor area (SMA, middle cingulate cortex and pre-central gyrus. There was a significant positive correlation between the evoked potential amplitude (EEG and the psychophysical perception of pain on the VAS. Conclusion The results of this study demonstrate the feasibility of recording contact heat evoked potentials with EEG during continuous and simultaneous fMRI. The combined use of the two methods can lead to identification of distinct patterns of brain

  19. Achieving Presence through Evoked Reality

    Science.gov (United States)

    Pillai, Jayesh S.; Schmidt, Colin; Richir, Simon

    2013-01-01

    The sense of “Presence” (evolving from “telepresence”) has always been associated with virtual reality research and is still an exceptionally mystifying constituent. Now the study of presence clearly spans over various disciplines associated with cognition. This paper attempts to put forth a concept that argues that it’s an experience of an “Evoked Reality (ER)” (illusion of reality) that triggers an “Evoked Presence (EP)” (sense of presence) in our minds. A Three Pole Reality Model is proposed to explain this phenomenon. The poles range from Dream Reality to Simulated Reality with Primary (Physical) Reality at the center. To demonstrate the relationship between ER and EP, a Reality-Presence Map is developed. We believe that this concept of ER and the proposed model may have significant applications in the study of presence, and in exploring the possibilities of not just virtual reality but also what we call “reality.” PMID:23550234

  20. Evoked Electromyographically Controlled Electrical Stimulation

    Directory of Open Access Journals (Sweden)

    Mitsuhiro Hayashibe

    2016-07-01

    Full Text Available Time-variant muscle responses under electrical stimulation (ES are often problematic for all the applications of neuroprosthetic muscle control. This situation limits the range of ES usage in relevant areas, mainly due to muscle fatigue and also to changes in stimulation electrode contact conditions, especially in transcutaneous ES. Surface electrodes are still the most widely used in noninvasive applications.Electrical field variations caused by changes in the stimulation contact condition markedly affect the resulting total muscle activation levels. Fatigue phenomena under functional electrical stimulation (FES are also well known source of time-varying characteristics coming from muscle response under ES. Therefore it is essential to monitor the actual muscle state and assess the expected muscle response by ES so as to improve the current ES system in favour of adaptive muscle-response-aware FES control. To deal with this issue, we have been studying a novel control technique using evoked electromyography (eEMG signals to compensate for these muscle time-variances under ES for stable neuroprosthetic muscle control. In this perspective article, I overview the background of this topic and highlight important points to be aware of when using ES to induce the desired muscle activation regardless of the time-variance. I also demonstrate how to deal with the common critical problem of ES to move toward robust neuroprosthetic muscle control with the Evoked Electromyographically Controlled Electrical Stimulation paradigm.

  1. Distinctive Citizenship

    DEFF Research Database (Denmark)

    Kaur, Ravinder

    2009-01-01

    -colonial citizenship within the mass of refugees. The core principle of the official resettlement policy was self-rehabilitation, that is, the ability to become a productive citizen of the new nation state without state intervention. Thus, the onus of performing a successful transition - from refugee to citizen - lay......The refugee, in India's Partition history, appears as an enigmatic construct - part pitiful, part heroic, though mostly shorn of agency - representing the surface of the human tragedy of Partition. Yet this archetype masks the undercurrent of social distinctions that produced hierarchies of post...... on the resourcefulness of the refugees rather than the state. This article traces the differing historical trajectories followed by 'state-dependent' and 'self-reliant' refugees in the making of modern citizenry in post-colonial India...

  2. Endothelial protective genes induced by statin are mimicked by ERK5 activation as triggered by a drug combination of FTI-277 and GGTI-298.

    Science.gov (United States)

    Chu, Uyen B; Duellman, Tyler; Weaver, Sara J; Tao, Yunting; Yang, Jay

    2015-07-01

    Statins are potent inhibitors of cholesterol biosynthesis and are clinically beneficial in preventing cardiovascular diseases, however, the therapeutic utility of these drugs is limited by myotoxicity. Here, we explored the mechanism of statin-mediated activation of ERK5 in the human endothelium with the goal of identifying compounds that confer endothelial protection but are nontoxic to muscle. An ERK5-one hybrid luciferase reporter transfected into COS-7 cells with pharmacological and molecular manipulations dissected the signaling pathway leading to statin activation of ERK5. qRT-PCR of HUVEC cells documented the transcriptional activation of endothelial-protective genes. Lastly, morphological and cellular ATP analysis, and induction of atrogin-1 in C2C12 myotubes were used to assess statin-induced myopathy. Statin activation of ERK5 is dependent on the cellular reduction of GGPPs. Furthermore, we found that the combination of FTI-277 (inhibitor of farnesyl transferase) and GGTI-298 (inhibitor of geranylgeranyl transferase I) mimicked the statin-mediated activation of ERK5. FTI-277 and GGTI-298 together recapitulated the beneficial effects of statins by transcriptionally upregulating anti-inflammatory mediators such as eNOS, THBD, and KLF2. Finally, C2C12 skeletal myotubes treated with both FTI-277 and GGTI-298 evoked less morphological and cellular changes recognized as biomarkers of statin-associated myopathy. Statin-induced endothelial protection and myopathy are mediated by distinct metabolic intermediates and co-inhibition of farnesyl transferase and geranylgeranyl transferase I confer endothelial protection without myopathy. The combinatorial FTI-277 and GGTI-298 drug regimen provides a promising alternative avenue for endothelial protection without myopathy. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Endothelial protective genes induced by statin is mimicked by FTI-277 and GGTI-298 drug combination-mediated ERK5 activation

    Science.gov (United States)

    Chu, Uyen B.; Duellman, Tyler; Weaver, Sara J.; Tao, Yunting; Yang, Jay

    2015-01-01

    Background Statins are potent inhibitors of cholesterol biosynthesis and are clinically beneficial in preventing cardiovascular diseases, however, the therapeutic utility of these drugs is limited by myotoxicity. Here, we explored the mechanism of statin-mediated activation of ERK5 in the human endothelium with the goal of identifying compounds that confer endothelial protection but are nontoxic to muscle. Methods An ERK5-one hybrid luciferase reporter transfected into COS-7 cells with pharmacological and molecular manipulations dissected the signaling pathway leading to statin activation of ERK5. qRT-PCR of HUVEC cells documented the transcriptional activation of endothelial-protective genes. Lastly, morphological and cellular ATP analysis, and induction of atrogin-1 in C2C12 myotubes were used to assess statin-induced myopathy. Results Statin activation of ERK5 is dependent on the cellular reduction of GGPPs. Furthermore, we found that the combination of FTI-277 (inhibitor of farnesyl transferase) and GGTI-298 (inhibitor of geranylgeranyl transferase I) mimicked the statin-mediated activation of ERK5. FTI-277 and GGTI-298 together recapitulated the beneficial effects of statins by transcriptionally upregulating anti-inflammatory mediators such as eNOS, THBD, and KLF2. Finally, C2C12 skeletal myotubes treated with both FTI-277 and GGTI-298 evoked less morphological and cellular changes recognized as biomarkers of statin-associated myopathy. Conclusions Statin-induced endothelial protection and myopathy are mediated by distinct metabolic intermediates and co-inhibition of farnesyl transferase and geranylgeranyl transferase I confer endothelial protection without myopathy. General Significance The combinatorial FTI-277 and GGTI-298 drug regimen provides a promising alternative avenue for endothelial protection without myopathy. PMID:25829196

  4. Human auditory evoked potentials. I - Evaluation of components

    Science.gov (United States)

    Picton, T. W.; Hillyard, S. A.; Krausz, H. I.; Galambos, R.

    1974-01-01

    Fifteen distinct components can be identified in the scalp recorded average evoked potential to an abrupt auditory stimulus. The early components occurring in the first 8 msec after a stimulus represent the activation of the cochlea and the auditory nuclei of the brainstem. The middle latency components occurring between 8 and 50 msec after the stimulus probably represent activation of both auditory thalamus and cortex but can be seriously contaminated by concurrent scalp muscle reflex potentials. The longer latency components occurring between 50 and 300 msec after the stimulus are maximally recorded over fronto-central scalp regions and seem to represent widespread activation of frontal cortex.

  5. RAGE Plays a Role in LPS-Induced NF-κB Activation and Endothelial Hyperpermeability.

    Science.gov (United States)

    Wang, Liqun; Wu, Jie; Guo, Xiaohua; Huang, Xuliang; Huang, Qiaobing

    2017-03-30

    Endothelial functional dysregulation and barrier disruption contribute to the initiation and development of sepsis. The receptor for advanced glycation end products (RAGE) has been demonstrated to be involved in the pathogenesis of sepsis. The present study aimed to investigate the role of RAGE in lipopolysaccharide (LPS)-induced nuclear factor-κB (NF-κB) activation in endothelial cells and the consequent endothelial hyperpermeability. LPS-induced upregulation of RAGE protein expression in human umbilical vein endothelial cells (HUVECs) was detected by western blotting. Activation of NF-κB was revealed using western blotting and immunofluorescent staining. LPS-elicited endothelial hyperpermeability was explored by transendothelial electrical resistance (TER) assay and endothelial monolayer permeability assay. The blocking antibody specific to RAGE was used to confirm the role of RAGE in LPS-mediated NF-κB activation and endothelial barrier disruption. We found that LPS upregulated the protein expression of RAGE in a dose- and time-dependent manner in HUVECs. Moreover, LPS triggered a significant phosphorylation and degradation of IκBα, as well as NF-κB p65 nuclear translocation. Moreover, we observed a significant increase in endothelial permeability after LPS treatment. However, the RAGE blocking antibody attenuated LPS-evoked NF-κB activation and endothelial hyperpermeability. Our results suggest that RAGE plays an important role in LPS-induced NF-κB activation and endothelial barrier dysfunction.

  6. Ocular Vestibular Evoked Myogenic Potentials

    Directory of Open Access Journals (Sweden)

    Felipe, Lilian

    2014-01-01

    Full Text Available Introduction Diagnostic testing of the vestibular system is an essential component of treating patients with balance dysfunction. Until recently, testing methods primarily evaluated the integrity of the horizontal semicircular canal, which is only a portion of the vestibular system. Recent advances in technology have afforded clinicians the ability to assess otolith function through vestibular evoked myogenic potential (VEMP testing. VEMP testing from the inferior extraocular muscles of the eye has been the subject of interest of recent research. Objective To summarize recent developments in ocular VEMP testing. Results Recent studies suggest that the ocular VEMP is produced by otolith afferents in the superior division of the vestibular nerve. The ocular VEMP is a short latency potential, composed of extraocular myogenic responses activated by sound stimulation and registered by surface electromyography via ipsilateral otolithic and contralateral extraocular muscle activation. The inferior oblique muscle is the most superficial of the six extraocular muscles responsible for eye movement. Therefore, measurement of ocular VEMPs can be performed easily by using surface electrodes on the skin below the eyes contralateral to the stimulated side. Conclusion This new variation of the VEMP procedure may supplement conventional testing in difficult to test populations. It may also be possible to use this technique to evaluate previously inaccessible information on the vestibular system.

  7. Evoked cavernous activity: neuroanatomic implications.

    Science.gov (United States)

    Yilmaz, U; Vicars, B; Yang, C C

    2009-01-01

    We investigated the autonomic innervation of the penis by using evoked cavernous activity (ECA). We recruited seven men with thoracic spinal cord injury (SCI) and sexual dysfunction, and six men who were scheduled to have pelvic surgery (PS), specifically non-nerve-sparing radical cystoprostatectomy. In the PS patients, ECA was performed both pre- and postoperatively. The left median nerve was electrically stimulated and ECA was recorded with two concentric electromyography needles placed into the right and left cavernous bodies. We simultaneously recorded hand and foot sympathetic skin responses (SSRs) as controls. In the SCI group, all but one patient had reproducible hand SSRs. None of these patients had ECA or foot SSRs. All the PS patients had reproducible ECA and SSRs, both preoperatively and postoperatively. There was no difference in the latency and amplitude measurements of ECA and SSRs in the postoperative compared with that of the pre-operative period (P>0.05). In conclusion, ECA is absent in men with SCI above the sympathetic outflow to the genitalia. In men, after radical pelvic surgery, ECA is preserved, indicating the preservation of sympathetic fibers.

  8. Evoked potentials in neuroinfections in children

    Directory of Open Access Journals (Sweden)

    V. N. Komantsev

    2013-01-01

    Full Text Available We present the results of the neurophysiological study in which 95 children with viral encephalitis and 30 children with meningitis (age from 2 up to 17 years undergo evoked potentials investigation. Some specific features of evoked potentials in neuroinfections have been shown to correlate with the course of disease and the age of the patients. We give a description of a logistic model of predicting outcomes in such patients by complex diagnostic method. We have found that evoked potentials may be successfully implemented in correcting the therapeutic strategies. Study of evoked potentials in neuroinfections in children can define the severity and extent of lesions and help to identify subclinical dysfunction and monitor the recovery processes under the therapy.

  9. Visual Evoked Potentials in Rett Syndrome

    Directory of Open Access Journals (Sweden)

    J. Gordon Millichap

    2015-11-01

    Full Text Available Investigators from the Boston Children's Hospital recorded pattern-reversal visual evoked potentials (VEPs in Mecp2 heterozygous female mice and in 34 girls with Rett syndrome (RTT.

  10. Vascular endothelial growth factor from embryonic status to cardiovascular pathology

    OpenAIRE

    Mohsen Azimi-Nezhad

    2014-01-01

    Vascular endothelial growth factor (VEGF) is a multifunctional cytokine with distinct functions in angiogenesis, lymphangiogenesis, vascular permeability, and hematopoiesis. VEGF is a highly conserved, disulfide-bonded dimeric glycoprotein of 34 to 45 kDa produced by several cell types including fibroblasts, neutrophils, endothelial cells, and peripheral blood mononuclear cells, particularly T lymphocytes and macrophages. Six VEGF isoforms are generated as a result of alternative splicing fro...

  11. Radiation-induced apoptosis in microvascular endothelial cells.

    OpenAIRE

    Langley, R. E.; Bump, E A; Quartuccio, S. G.; Medeiros, D; Braunhut, S. J.

    1997-01-01

    The response of the microvasculature to ionizing radiation is thought to be an important factor in the overall response of both normal tissues and tumours. It has recently been reported that basic fibroblast growth factor (bFGF), a potent mitogen for endothelial cells, protects large vessel endothelial cells from radiation-induced apoptosis in vitro. Microvessel cells are phenotypically distinct from large vessel cells. We studied the apoptotic response of confluent monolayers of capillary en...

  12. The Central Role of Endothelial Dysfunction in Cardiorenal Syndrome.

    Science.gov (United States)

    Zhang, Jun; Bottiglieri, Teodoro; McCullough, Peter A

    2017-02-01

    Endothelial dysfunction (ED) has emerged as a critical process in cardiorenal syndrome (CRS). The concept that ED is closely linked with cardiac and renal dysfunction has become an important target for CRS-related research and clinical practice. The sequence of events leading to ED is initiated by type I endothelial activation (almost immediately) and type II endothelial activation (over hours, days, and even months), followed by endothelial apoptosis and endothelial necrosis. The fact that ED is a continual cellular event divides this process into reversible ED (endothelial activation) and irreversible ED (endothelial apoptosis and necrosis). This basic research-defined concept may have clinical implications. Although most antihypertensive drugs (ACE inhibitors, statins, etc.) are effective in patients with hypertension and diabetes, some of them have proved to be ineffective, which may partly be attributed to irreversible ED. Even though the etiology of ED consists mainly of asymmetric dimethylarginine, nitric oxide, oxidative stress, and anti-endothelial cell antibodies, many other inducers of ED have been identified. In addition, a distinct role of ED has been reported for each type of CRS in humans. Further study is warranted to prove whether ED holds promise as a pharmacological target in CRS patients.

  13. Predictability of painful stimulation modulates the somatosensory-evoked potential in the rat.

    Directory of Open Access Journals (Sweden)

    Manon W H Schaap

    Full Text Available Somatosensory-evoked potentials (SEPs are used in humans and animals to increase knowledge about nociception and pain. Since the SEP in humans increases when noxious stimuli are administered unpredictably, predictability potentially influences the SEP in animals as well. To assess the effect of predictability on the SEP in animals, classical fear conditioning was applied to compare SEPs between rats receiving SEP-evoking electrical stimuli either predictably or unpredictably. As in humans, the rat's SEP increased when SEP-evoking stimuli were administered unpredictably. These data support the hypothesis that the predictability of noxious stimuli plays a distinctive role in the processing of these stimuli in animals. The influence of predictability should be considered when studying nociception and pain in animals. Additionally, this finding suggests that animals confronted with (unpredictable noxious stimuli can be used to investigate the mechanisms underlying the influence of predictability on central processing of noxious stimuli.

  14. Cortical modulation of short-latency TMS-evoked potentials

    Directory of Open Access Journals (Sweden)

    Domenica eVeniero

    2013-01-01

    Full Text Available Transcranial magnetic stimulation - electroencephalogram (TMS-EEG co-registration offers the opportunity to test reactivity of brain areas across distinct conditions through TMS-evoked potentials (TEPs. Several TEPs have been described, their functional meaning being largely unknown. In particular, short-latency potentials peaking at 5 (P5 and 8 (N8 ms after the TMS pulse have been recently described, but because of their huge amplitude, the problem of whether their origin is cortical or not has been opened. To gain information about these components, we employed a protocol that modulates primary motor cortex excitability (MI through an exclusively cortical phenomena: low frequency stimulation of premotor area (PMC. TMS was applied simultaneously with EEG recording from 70 electrodes. Amplitude of TEPs evoked by 200 single-pulses TMS delivered over MI at 110% of resting motor threshold was measured before and after applying 900 TMS conditioning stimuli to left premotor cortex with 1 Hz repetition rate. Single subject analyses showed reduction in TEPs amplitude after PMC conditioning in a sample of participants and increase in TEPs amplitude in two subjects. No effects were found on corticospinal excitability as recorded by motor evoked potentials (MEPs. Furthermore, correlation analysis showed an inverse relation between the effects of the conditioning protocol on P5-N8 complex amplitude and MEPs amplitude. Because the effects of the used protocol have been ascribed to a cortical interaction between premotor area and MI, we suggest that despite the sign of P5-N8 amplitude modulation is not consistent across participant, this modulation could indicate, at least in part, their cortical origin. We conclude that with an accurate experimental procedure early-latency components can be used to evaluate the reactivity of the stimulated cortex.

  15. Characterization of music-evoked autobiographical memories.

    Science.gov (United States)

    Janata, Petr; Tomic, Stefan T; Rakowski, Sonja K

    2007-11-01

    Despite music's prominence in Western society and its importance to individuals in their daily lives, very little is known about the memories and emotions that are often evoked when hearing a piece of music from one's past. We examined the content of music-evoked autobiographical memories (MEAMs) using a novel approach for selecting stimuli from a large corpus of popular music, in both laboratory and online settings. A set of questionnaires probed the cognitive and affective properties of the evoked memories. On average, 30% of the song presentations evoked autobiographical memories, and the majority of songs also evoked various emotions, primarily positive, that were felt strongly. The third most common emotion was nostalgia. Analyses of written memory reports found both general and specific levels of autobiographical knowledge to be represented, and several social and situational contexts for memory formation were common across many memories. The findings indicate that excerpts of popular music serve as potent stimuli for studying the structure of autobiographical memories.

  16. Autocrine VEGF isoforms differentially regulate endothelial cell behavior

    Directory of Open Access Journals (Sweden)

    Hideki Yamamoto

    2016-09-01

    Full Text Available Vascular endothelial growth factor A (VEGF is involved in all the essential biology of endothelial cells, from proliferation to vessel function, by mediating intercellular interactions and monolayer integrity. It is expressed as three major alternative spliced variants. In mice, these are VEGF120, VEGF164, and VEGF188, each with different affinities for extracellular matrices and cell surfaces, depending on the inclusion of heparin-binding sites, encoded by exons 6 and 7. To determine the role of each VEGF isoform in endothelial homeostasis, we compared phenotypes of primary endothelial cells isolated from lungs of mice expressing single VEGF isoforms in normoxic and hypoxic conditions. The differential expression and distribution of VEGF isoforms affect endothelial cell functions, such as proliferation, adhesion, migration and integrity, which are dependent on the stability of and affinity to VEGF receptor 2 (VEGFR2. We found a correlation between autocrine VEGF164 and VEGFR2 stability, which is also associated with increased expression of proteins involved in cell adhesion. Endothelial cells expressing only VEGF188, which localizes to extracellular matrices or cell surfaces, presented a mesenchymal morphology and weakened monolayer integrity. Cells expressing only VEGF120 lacked stable VEGFR2 and dysfunctional downstream processes, rendering the cells unviable. Endothelial cells expressing these different isoforms in isolation also had differing rates of apoptosis, proliferation, and signaling via nitric oxide (NO synthesis. These data indicate that autocrine signaling of each VEGF isoform has unique functions on endothelial homeostasis and response to hypoxia, due to both distinct VEGF distribution and VEGFR2 stability, which appears to be, at least partly, affected by differential NO production. This study demonstrates that each autocrine VEGF isoform has a distinct effect on downstream functions, namely VEGFR2-regulated endothelial cell

  17. Brain correlates of music-evoked emotions.

    Science.gov (United States)

    Koelsch, Stefan

    2014-03-01

    Music is a universal feature of human societies, partly owing to its power to evoke strong emotions and influence moods. During the past decade, the investigation of the neural correlates of music-evoked emotions has been invaluable for the understanding of human emotion. Functional neuroimaging studies on music and emotion show that music can modulate activity in brain structures that are known to be crucially involved in emotion, such as the amygdala, nucleus accumbens, hypothalamus, hippocampus, insula, cingulate cortex and orbitofrontal cortex. The potential of music to modulate activity in these structures has important implications for the use of music in the treatment of psychiatric and neurological disorders.

  18. Evoking prescribed spike times in stochastic neurons

    Science.gov (United States)

    Doose, Jens; Lindner, Benjamin

    2017-09-01

    Single cell stimulation in vivo is a powerful tool to investigate the properties of single neurons and their functionality in neural networks. We present a method to determine a cell-specific stimulus that reliably evokes a prescribed spike train with high temporal precision of action potentials. We test the performance of this stimulus in simulations for two different stochastic neuron models. For a broad range of parameters and a neuron firing with intermediate firing rates (20-40 Hz) the reliability in evoking the prescribed spike train is close to its theoretical maximum that is mainly determined by the level of intrinsic noise.

  19. Activation of Endothelial Nitric Oxide (eNOS Occurs through Different Membrane Domains in Endothelial Cells.

    Directory of Open Access Journals (Sweden)

    Jason Tran

    Full Text Available Endothelial cells respond to a large range of stimuli including circulating lipoproteins, growth factors and changes in haemodynamic mechanical forces to regulate the activity of endothelial nitric oxide synthase (eNOS and maintain blood pressure. While many signalling pathways have been mapped, the identities of membrane domains through which these signals are transmitted are less well characterized. Here, we manipulated bovine aortic endothelial cells (BAEC with cholesterol and the oxysterol 7-ketocholesterol (7KC. Using a range of microscopy techniques including confocal, 2-photon, super-resolution and electron microscopy, we found that sterol enrichment had differential effects on eNOS and caveolin-1 (Cav1 colocalisation, membrane order of the plasma membrane, caveolae numbers and Cav1 clustering. We found a correlation between cholesterol-induced condensation of the plasma membrane and enhanced high density lipoprotein (HDL-induced eNOS activity and phosphorylation suggesting that cholesterol domains, but not individual caveolae, mediate HDL stimulation of eNOS. Vascular endothelial growth factor (VEGF-induced and shear stress-induced eNOS activity was relatively independent of membrane order and may be predominantly controlled by the number of caveolae on the cell surface. Taken together, our data suggest that signals that activate and phosphorylate eNOS are transmitted through distinct membrane domains in endothelial cells.

  20. Activation of Endothelial Nitric Oxide (eNOS) Occurs through Different Membrane Domains in Endothelial Cells.

    Science.gov (United States)

    Tran, Jason; Magenau, Astrid; Rodriguez, Macarena; Rentero, Carles; Royo, Teresa; Enrich, Carlos; Thomas, Shane R; Grewal, Thomas; Gaus, Katharina

    2016-01-01

    Endothelial cells respond to a large range of stimuli including circulating lipoproteins, growth factors and changes in haemodynamic mechanical forces to regulate the activity of endothelial nitric oxide synthase (eNOS) and maintain blood pressure. While many signalling pathways have been mapped, the identities of membrane domains through which these signals are transmitted are less well characterized. Here, we manipulated bovine aortic endothelial cells (BAEC) with cholesterol and the oxysterol 7-ketocholesterol (7KC). Using a range of microscopy techniques including confocal, 2-photon, super-resolution and electron microscopy, we found that sterol enrichment had differential effects on eNOS and caveolin-1 (Cav1) colocalisation, membrane order of the plasma membrane, caveolae numbers and Cav1 clustering. We found a correlation between cholesterol-induced condensation of the plasma membrane and enhanced high density lipoprotein (HDL)-induced eNOS activity and phosphorylation suggesting that cholesterol domains, but not individual caveolae, mediate HDL stimulation of eNOS. Vascular endothelial growth factor (VEGF)-induced and shear stress-induced eNOS activity was relatively independent of membrane order and may be predominantly controlled by the number of caveolae on the cell surface. Taken together, our data suggest that signals that activate and phosphorylate eNOS are transmitted through distinct membrane domains in endothelial cells.

  1. Transient Evoked aotacoustic emissions otologically normal adults

    African Journals Online (AJOL)

    ABUTH

    Objective: To examine the effects of aging on the existence of transient evoked otoacoustic emissions in normal adult. Material and methods 40 ... wax or any middle ear pathology which might affect the recording at TEOAEs. After that, ... related to decreased hearing sensitivity and are independent of aging, Previous studies.

  2. Neural correlates of evoked phantom limb sensations.

    Science.gov (United States)

    Andoh, J; Diers, M; Milde, C; Frobel, C; Kleinböhl, D; Flor, H

    2017-05-01

    Previous work showed the existence of changes in the topographic organization within the somatosensory cortex (SI) in amputees with phantom limb pain, however, the link between nonpainful phantom sensations such as cramping or tingling or the percept of the limb and cortical changes is less clear. We used functional magnetic resonance imaging (fMRI) in a highly selective group of limb amputees who experienced inducible and reproducible nonpainful phantom sensations. A standardized procedure was used to locate body sites eliciting phantom sensations in each amputee. Selected body sites that could systematically evoke phantom sensations were stimulated using electrical pulses in order to induce phasic phantom sensations. Homologous body parts were also stimulated in a group of matched controls. Activations related to evoked phantom sensations were found bilaterally in SI and the intraparietal sulci (IPS), which significantly correlated with the intensity of evoked phantom sensations. In addition, we found differences in intra- and interhemispheric interaction between amputees and controls during evoked phantom sensations. We assume that phantom sensations might be associated with a functional decoupling between bilateral SI and IPS, possibly resulting from transcallosal reorganization mechanisms following amputation. Copyright © 2017. Published by Elsevier B.V.

  3. The endothelial border to health

    DEFF Research Database (Denmark)

    Hansen, Nina Wærling; Hansen, Anker Jon; Sams, Anette

    2017-01-01

    by hyperglycemic events because the endothelium transduces “high glucose” signaling into significant pathophysiological phenomena leading to reduced endothelial barrier function, compromised vascular tone regulation and inflammation (e.g., cytokine secretion and RAGE activation). In addition, endothelial...

  4. Visually Evoked Spiking Evolves While Spontaneous Ongoing Dynamics Persist

    DEFF Research Database (Denmark)

    Huys, Raoul; Jirsa, Viktor K; Darokhan, Ziauddin

    2016-01-01

    attractor. Its existence guarantees that evoked spiking return to the spontaneous state. However, the spontaneous ongoing spiking state and the visual evoked spiking states are qualitatively different and are separated by a threshold (separatrix). The functional advantage of this organization...

  5. Temperature differentially facilitates spontaneous but not evoked glutamate release from cranial visceral primary afferents.

    Directory of Open Access Journals (Sweden)

    Jessica A Fawley

    Full Text Available Temperature is fundamentally important to all biological functions including synaptic glutamate release. Vagal afferents from the solitary tract (ST synapse on second order neurons in the nucleus of the solitary tract, and glutamate release at this first central synapse controls autonomic reflex function. Expression of the temperature-sensitive Transient Receptor Potential Vanilloid Type 1 receptor separates ST afferents into C-fibers (TRPV1+ and A-fibers (TRPV1-. Action potential-evoked glutamate release is similar between C- and A-fiber afferents, but TRPV1 expression facilitates a second form of synaptic glutamate release in C-fibers by promoting substantially more spontaneous glutamate release. The influence of temperature on different forms of glutamate release is not well understood. Here we tested how temperature impacts the generation of evoked and spontaneous release of glutamate and its relation to TRPV1 expression. In horizontal brainstem slices of rats, activation of ST primary afferents generated synchronous evoked glutamate release (ST-eEPSCs at constant latency whose amplitude reflects the probability of evoked glutamate release. The frequency of spontaneous EPSCs in these same neurons measured the probability of spontaneous glutamate release. We measured both forms of glutamate from each neuron during ramp changes in bath temperature of 4-5 °C. Spontaneous glutamate release from TRPV1+ closely tracked with these thermal changes indicating changes in the probability of spontaneous glutamate release. In the same neurons, temperature changed axon conduction registered as latency shifts but ST-eEPSC amplitudes were constant and independent of TRPV1 expression. These data indicate that TRPV1-operated glutamate release is independent of action potential-evoked glutamate release in the same neurons. Together, these support the hypothesis that evoked and spontaneous glutamate release originate from two pools of vesicles that are

  6. Differentiation state determines neural effects on microvascular endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Muffley, Lara A., E-mail: muffley@u.washington.edu [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States); Pan, Shin-Chen, E-mail: pansc@mail.ncku.edu.tw [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States); Smith, Andria N., E-mail: gnaunderwater@gmail.com [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States); Ga, Maricar, E-mail: marga16@uw.edu [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States); Hocking, Anne M., E-mail: ahocking@u.washington.edu [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States); Gibran, Nicole S., E-mail: nicoleg@u.washington.edu [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States)

    2012-10-01

    Growing evidence indicates that nerves and capillaries interact paracrinely in uninjured skin and cutaneous wounds. Although mature neurons are the predominant neural cell in the skin, neural progenitor cells have also been detected in uninjured adult skin. The aim of this study was to characterize differential paracrine effects of neural progenitor cells and mature sensory neurons on dermal microvascular endothelial cells. Our results suggest that neural progenitor cells and mature sensory neurons have unique secretory profiles and distinct effects on dermal microvascular endothelial cell proliferation, migration, and nitric oxide production. Neural progenitor cells and dorsal root ganglion neurons secrete different proteins related to angiogenesis. Specific to neural progenitor cells were dipeptidyl peptidase-4, IGFBP-2, pentraxin-3, serpin f1, TIMP-1, TIMP-4 and VEGF. In contrast, endostatin, FGF-1, MCP-1 and thrombospondin-2 were specific to dorsal root ganglion neurons. Microvascular endothelial cell proliferation was inhibited by dorsal root ganglion neurons but unaffected by neural progenitor cells. In contrast, microvascular endothelial cell migration in a scratch wound assay was inhibited by neural progenitor cells and unaffected by dorsal root ganglion neurons. In addition, nitric oxide production by microvascular endothelial cells was increased by dorsal root ganglion neurons but unaffected by neural progenitor cells. -- Highlights: Black-Right-Pointing-Pointer Dorsal root ganglion neurons, not neural progenitor cells, regulate microvascular endothelial cell proliferation. Black-Right-Pointing-Pointer Neural progenitor cells, not dorsal root ganglion neurons, regulate microvascular endothelial cell migration. Black-Right-Pointing-Pointer Neural progenitor cells and dorsal root ganglion neurons do not effect microvascular endothelial tube formation. Black-Right-Pointing-Pointer Dorsal root ganglion neurons, not neural progenitor cells, regulate

  7. Wiener kernel analysis of a noise-evoked otoacoustic emission

    NARCIS (Netherlands)

    van Dijk, P; Maat, A; Wit, H P

    1997-01-01

    In one specimen of the frog species, Rana esculenta, the following were measured: (1) a spontaneous otoacoustic emission; (2) a click-evoked otoacoustic emissions; and (3) a noise evoked otoacoustic emission. From the noise evoked emission response, a first-and a second-order Wiener kernel and the

  8. Thought-evoking approaches in engineering problems

    CERN Document Server

    2014-01-01

    In creating the value-added product in not distant future, it is necessary and inevitable to establish a holistic and though-evoking approach to the engineering problem, which should be at least associated with the inter-disciplinary knowledge and thought processes across the whole engineering spheres. It is furthermore desirable to integrate it with trans-disciplinary aspects ranging from manufacturing culture, through liberal-arts engineering, and industrial sociology.   The thought-evoking approach can be exemplified and typified by representative engineering problems: unveiling essential features in ‘Tangential Force Ratio and Interface Pressure’, prototype development for ‘Bio-mimetic Needle’ and application of ‘Water-jet Machining to Artificial Hip Joint’, product innovation in ‘Heat Sink for Computer’, application of ‘Graph Theory’ to similarity evaluation of production systems, leverage among reciprocity attributes in ‘Industrial and Engineering Designs for Machine Enclosure’,...

  9. Methodology for self-report of rest pain (or spontaneous pain) vs evoked pain in chronic neuropathic conditions: a prospective observational pilot study

    OpenAIRE

    David He; Brian Grant; Ronald R. Holden; Ian Gilron

    2017-01-01

    Abstract. Introduction:. The distinction between pain at rest and pain evoked by touch or movement has important clinical implications and may be associated with different mechanisms. However, current methods of clinical pain assessment pay little attention to directly distinguishing between these contrasting components of symptom burden. Objectives:. We developed the 10-item “Functional Impact of Neuropathic Evoked and Spontaneous Symptom Evaluation” questionnaire designed to distinguish ...

  10. Music-Evoked Emotions-Current Studies.

    Science.gov (United States)

    Schaefer, Hans-Eckhardt

    2017-01-01

    The present study is focused on a review of the current state of investigating music-evoked emotions experimentally, theoretically and with respect to their therapeutic potentials. After a concise historical overview and a schematic of the hearing mechanisms, experimental studies on music listeners and on music performers are discussed, starting with the presentation of characteristic musical stimuli and the basic features of tomographic imaging of emotional activation in the brain, such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), which offer high spatial resolution in the millimeter range. The progress in correlating activation imaging in the brain to the psychological understanding of music-evoked emotion is demonstrated and some prospects for future research are outlined. Research in psychoneuroendocrinology and molecular markers is reviewed in the context of music-evoked emotions and the results indicate that the research in this area should be intensified. An assessment of studies involving measuring techniques with high temporal resolution down to the 10 ms range, as, e.g., electroencephalography (EEG), event-related brain potentials (ERP), magnetoencephalography (MEG), skin conductance response (SCR), finger temperature, and goose bump development (piloerection) can yield information on the dynamics and kinetics of emotion. Genetic investigations reviewed suggest the heredity transmission of a predilection for music. Theoretical approaches to musical emotion are directed to a unified model for experimental neurological evidence and aesthetic judgment. Finally, the reports on musical therapy are briefly outlined. The study concludes with an outlook on emerging technologies and future research fields.

  11. Quantum Distinction: Quantum Distinctiones!

    OpenAIRE

    Zeps, Dainis

    2009-01-01

    10 pages; How many distinctions, in Latin, quantum distinctiones. We suggest approach of anthropic principle based on anthropic reference system which should be applied equally both in theoretical physics and in mathematics. We come to principle that within reference system of life subject of mathematics (that of thinking) should be equated with subject of physics (that of nature). For this reason we enter notions of series of distinctions, quantum distinction, and argue that quantum distinct...

  12. Sympathetic Innervation Promotes Arterial Fate by Enhancing Endothelial ERK Activity.

    Science.gov (United States)

    Pardanaud, Luc; Pibouin-Fragner, Laurence; Dubrac, Alexandre; Mathivet, Thomas; English, Isabel; Brunet, Isabelle; Simons, Michael; Eichmann, Anne

    2016-08-19

    Arterial endothelial cells are morphologically, functionally, and molecularly distinct from those found in veins and lymphatic vessels. How arterial fate is acquired during development and maintained in adult vessels is incompletely understood. We set out to identify factors that promote arterial endothelial cell fate in vivo. We developed a functional assay, allowing us to monitor and manipulate arterial fate in vivo, using arteries isolated from quails that are grafted into the coelom of chick embryos. Endothelial cells migrate out from the grafted artery, and their colonization of host arteries and veins is quantified. Here we show that sympathetic innervation promotes arterial endothelial cell fate in vivo. Removal of sympathetic nerves decreases arterial fate and leads to colonization of veins, whereas exposure to sympathetic nerves or norepinephrine imposes arterial fate. Mechanistically, sympathetic nerves increase endothelial ERK (extracellular signal-regulated kinase) activity via adrenergic α1 and α2 receptors. These findings show that sympathetic innervation promotes arterial endothelial fate and may lead to novel approaches to improve arterialization in human disease. © 2016 American Heart Association, Inc.

  13. Nanomedicines for Endothelial Disorders

    OpenAIRE

    Chung, Bomy Lee; Toth, Michael J.; Kamaly, Nazila; Sei, Yoshitaka J.; Becraft, Jacob; Mulder, Willem J. M.; Fayad, Zahi A; Farokhzad, Omid C.; Kim, YongTae; Langer, Robert

    2015-01-01

    The endothelium lines the internal surfaces of blood and lymphatic vessels and has a critical role in maintaining homeostasis. Endothelial dysfunction is involved in the pathology of many diseases and conditions, including disorders such as diabetes, cardiovascular diseases, and cancer. Given this common etiology in a range of diseases, medicines targeting an impaired endothelium can strengthen the arsenal of therapeutics. Nanomedicine – the application of nanotechnology to healthcare – prese...

  14. Music-Evoked Emotions—Current Studies

    Directory of Open Access Journals (Sweden)

    Hans-Eckhardt Schaefer

    2017-11-01

    Full Text Available The present study is focused on a review of the current state of investigating music-evoked emotions experimentally, theoretically and with respect to their therapeutic potentials. After a concise historical overview and a schematic of the hearing mechanisms, experimental studies on music listeners and on music performers are discussed, starting with the presentation of characteristic musical stimuli and the basic features of tomographic imaging of emotional activation in the brain, such as functional magnetic resonance imaging (fMRI and positron emission tomography (PET, which offer high spatial resolution in the millimeter range. The progress in correlating activation imaging in the brain to the psychological understanding of music-evoked emotion is demonstrated and some prospects for future research are outlined. Research in psychoneuroendocrinology and molecular markers is reviewed in the context of music-evoked emotions and the results indicate that the research in this area should be intensified. An assessment of studies involving measuring techniques with high temporal resolution down to the 10 ms range, as, e.g., electroencephalography (EEG, event-related brain potentials (ERP, magnetoencephalography (MEG, skin conductance response (SCR, finger temperature, and goose bump development (piloerection can yield information on the dynamics and kinetics of emotion. Genetic investigations reviewed suggest the heredity transmission of a predilection for music. Theoretical approaches to musical emotion are directed to a unified model for experimental neurological evidence and aesthetic judgment. Finally, the reports on musical therapy are briefly outlined. The study concludes with an outlook on emerging technologies and future research fields.

  15. Music-Evoked Emotions—Current Studies

    Science.gov (United States)

    Schaefer, Hans-Eckhardt

    2017-01-01

    The present study is focused on a review of the current state of investigating music-evoked emotions experimentally, theoretically and with respect to their therapeutic potentials. After a concise historical overview and a schematic of the hearing mechanisms, experimental studies on music listeners and on music performers are discussed, starting with the presentation of characteristic musical stimuli and the basic features of tomographic imaging of emotional activation in the brain, such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), which offer high spatial resolution in the millimeter range. The progress in correlating activation imaging in the brain to the psychological understanding of music-evoked emotion is demonstrated and some prospects for future research are outlined. Research in psychoneuroendocrinology and molecular markers is reviewed in the context of music-evoked emotions and the results indicate that the research in this area should be intensified. An assessment of studies involving measuring techniques with high temporal resolution down to the 10 ms range, as, e.g., electroencephalography (EEG), event-related brain potentials (ERP), magnetoencephalography (MEG), skin conductance response (SCR), finger temperature, and goose bump development (piloerection) can yield information on the dynamics and kinetics of emotion. Genetic investigations reviewed suggest the heredity transmission of a predilection for music. Theoretical approaches to musical emotion are directed to a unified model for experimental neurological evidence and aesthetic judgment. Finally, the reports on musical therapy are briefly outlined. The study concludes with an outlook on emerging technologies and future research fields. PMID:29225563

  16. Do ambient urban odors evoke basic emotions?

    Directory of Open Access Journals (Sweden)

    Sandra Theresia Weber-Glass

    2014-04-01

    Full Text Available Fragrances, such as plant odors, have been shown to evoke autonomic response patterns associated with Ekman’s (Ekman et al., 1983 basic emotions happiness, surprise, anger, fear, sadness and disgust. Inducing positive emotions by odors in highly frequented public spaces could serve to improve the quality of life in urban environments. Thus, the present study evaluated the potency of ambient odors connoted with an urban environment to evoke basic emotions on an autonomic and cognitive response level. Synthetic mixtures representing the odors of disinfectant, candles / bees wax, summer air, burnt smell, vomit and musty smell as well as odorless water as a control were presented five times in random order to 30 healthy, non-smoking human subjects with intact sense of smell. Skin temperature, skin conductance, breathing rate, forearm muscle activity, blink rate and heart rate were recorded simultaneously. Subjects rated the odors in terms of pleasantness, intensity and familiarity and gave verbal labels to each odor as well as cognitive associations with the basic emotions. The results showed that the amplitude of the skin conductance response varied as a function of odor presentation. Burnt smell and vomit elicited significantly higher electrodermal responses than summer air. Also, a negative correlation was revealed between the amplitude of the skin conductance response and hedonic odor valence indicating that the magnitude of the electrodermal response increased with odor unpleasantness. The analysis of the cognitive associations between odors and basic emotions showed that candles / bees wax and summer air were specifically associated with happiness whereas burnt smell and vomit were uniquely associated with disgust. Our findings suggest that city odors may evoke specific cognitive associations of basic emotions and that autonomic activity elicited by such odors is related to odor hedonics.

  17. Somatosensory evoked response: application in neurology

    Directory of Open Access Journals (Sweden)

    Carlos A. M. Guerreiro

    1982-03-01

    Full Text Available One technique used for short-latency somatosensory evoked response (SER is described. SER following nerve stimulation is a unique non-invasive, clinical test used to evaluate the somatosensory pathways. It tests the physiological function of the median nerve, the brachial plexus, the C6-7 cervical roots, cervical spinal cord, the cuneate nuclei, the medial lemniscus, the thalamus, and the contralateral sensory cortex. It has been shown to be a reliable and useful clinical test partiicularly in multiple sclerosis and comatose patients. The promising technique of SER following peroneal nerve stimulation is mentioned.

  18. Endothelial RIG-I activation impairs endothelial function

    Energy Technology Data Exchange (ETDEWEB)

    Asdonk, Tobias, E-mail: tobias.asdonk@ukb.uni-bonn.de [Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Motz, Inga; Werner, Nikos [Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Coch, Christoph; Barchet, Winfried; Hartmann, Gunther [Institute for Clinical Chemistry and Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Nickenig, Georg; Zimmer, Sebastian [Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany)

    2012-03-30

    Highlights: Black-Right-Pointing-Pointer RIG-I activation impairs endothelial function in vivo. Black-Right-Pointing-Pointer RIG-I activation alters HCAEC biology in vitro. Black-Right-Pointing-Pointer EPC function is affected by RIG-I stimulation in vitro. -- Abstract: Background: Endothelial dysfunction is a crucial part of the chronic inflammatory atherosclerotic process and is mediated by innate and acquired immune mechanisms. Recent studies suggest that pattern recognition receptors (PRR) specialized in immunorecognition of nucleic acids may play an important role in endothelial biology in a proatherogenic manner. Here, we analyzed the impact of endothelial retinoic acid inducible gene I (RIG-I) activation upon vascular endothelial biology. Methods and results: Wild type mice were injected intravenously with 32.5 {mu}g of the RIG-ligand 3pRNA (RNA with triphosphate at the 5 Prime end) or polyA control every other day for 7 days. In 3pRNA-treated mice, endothelium-depended vasodilation was significantly impaired, vascular oxidative stress significantly increased and circulating endothelial microparticle (EMP) numbers significantly elevated compared to controls. To gain further insight in RIG-I dependent endothelial biology, cultured human coronary endothelial cells (HCAEC) and endothelial progenitor cells (EPC) were stimulated in vitro with 3pRNA. Both cells types express RIG-I and react with receptor upregulation upon stimulation. Reactive oxygen species (ROS) formation is enhanced in both cell types, whereas apoptosis and proliferation is not significantly affected in HCAEC. Importantly, HCAEC release significant amounts of proinflammatory cytokines in response to RIG-I stimulation. Conclusion: This study shows that activation of the cytoplasmatic nucleic acid receptor RIG-I leads to endothelial dysfunction. RIG-I induced endothelial damage could therefore be an important pathway in atherogenesis.

  19. Evoked potentials in pediatric cerebral malaria

    Directory of Open Access Journals (Sweden)

    Minal Bhanushali

    2011-08-01

    Full Text Available Cortical evoked potentials (EP provide localized data regarding brain function and may offer prognostic information and insights into the pathologic mechanisms of malariamediated cerebral injury. As part of a prospective cohort study, we obtained somatosensory evoked potentials (SSEPs and brainstem auditory EPs (AEPs within 24 hours of admission on 27 consecutive children admitted with cerebral malaria (CM. Children underwent follow-up for 12 months to determine if they had any long term neurologic sequelae. EPs were obtained in 27 pediatric CM admissions. Two children died. Among survivors followed an average of 514 days, 7/25 (28.0% had at least one adverse neurologic outcome. Only a single subject had absent cortical EPs on admission and this child had a good neurologic outcome. Among pediatric CM survivors, cortical EPs are generally intact and do not predict adverse neurologic outcomes. Further study is needed to determine if alterations in cortical EPs can be used to predict a fatal outcome in CM.

  20. [Personality dimensions and cerebral evoked potential].

    Science.gov (United States)

    Camposano, S; Alvarez, C; Lolas, F

    1994-12-01

    Eysenck's personality theory postulates 3 orthogonal dimensions of personality: extraversion (E), neuroticism (N) and psychoticism (P), predicting conductual and physiological predispositions to suffer mental illness. Biological bases of Eysenck's personality traits have been documented electrophysiologically. Psychoticism, the latest described dimension, is controverted, since there is some evidence of common factors with the other two. In order to assess the relation between Eysenck's dimensions and sensorial reactivity and information encoding processes we studied 20 healthy young subjects (mean age 28.5 years) with flash visual cortical evoked potentials (VEP, 3 intensities, peak to peak amplitude of III, IV-V-VI, VII components), and auditory cognitive evoked potentials (odd ball paradigm, P300 latency). There was a positive correlation between N and P dimensions (Spearman, r = 0.52), between N and VEP amplitude at high intensity (r = 0.58) and a negative correlation between E and P300 latency (r = 0.58). In short we found that P is not an independent dimension, but is related to sensorial reactivity. E dimension was related to encoding processes supporting Eysenck's observations about memory and learning differences.

  1. Long Latency Auditory Evoked Potentials during Meditation.

    Science.gov (United States)

    Telles, Shirley; Deepeshwar, Singh; Naveen, Kalkuni Visweswaraiah; Pailoor, Subramanya

    2015-10-01

    The auditory sensory pathway has been studied in meditators, using midlatency and short latency auditory evoked potentials. The present study evaluated long latency auditory evoked potentials (LLAEPs) during meditation. Sixty male participants, aged between 18 and 31 years (group mean±SD, 20.5±3.8 years), were assessed in 4 mental states based on descriptions in the traditional texts. They were (a) random thinking, (b) nonmeditative focusing, (c) meditative focusing, and (d) meditation. The order of the sessions was randomly assigned. The LLAEP components studied were P1 (40-60 ms), N1 (75-115 ms), P2 (120-180 ms), and N2 (180-280 ms). For each component, the peak amplitude and peak latency were measured from the prestimulus baseline. There was significant decrease in the peak latency of the P2 component during and after meditation (Pmeditation facilitates the processing of information in the auditory association cortex, whereas the number of neurons recruited was smaller in random thinking and non-meditative focused thinking, at the level of the secondary auditory cortex, auditory association cortex and anterior cingulate cortex. © EEG and Clinical Neuroscience Society (ECNS) 2014.

  2. New perspectives on vestibular evoked myogenic potentials.

    Science.gov (United States)

    Rosengren, Sally M; Kingma, Herman

    2013-02-01

    Although the vestibular evoked myogenic potential (VEMP) measured from the cervical muscles (cVEMP, cervical VEMP) is well described and has documented clinical utility, its analogue recorded from the extraocular muscles (oVEMP, ocular VEMP) has been described only recently and is currently emerging as an additional test of otolith function. This review will, therefore, summarize recent developments in VEMP research with a focus on the oVEMP. Recent studies suggest that the oVEMP is produced by otolith afferents in the superior vestibular nerve division, whereas the cVEMP evoked by sound is thought to be an inferior vestibular nerve reflex. Correspondingly, the oVEMP correlates better with caloric and subjective visual vertical tests than sound-cVEMPs. cVEMPs are more complicated than often thought, as shown by the presence of crossed responses and conflicting results of recent vibration studies. Altered inner ear mechanics produced by the vestibular diseases superior semicircular canal dehiscence and Ménière's disease lead to changes in the preferred frequency of the oVEMP and cVEMP. The oVEMP provides complementary diagnostic information to the cVEMP and is likely to be a useful addition to the diagnostic test battery in neuro-otology.

  3. Speech Evoked Auditory Brainstem Response in Stuttering

    Directory of Open Access Journals (Sweden)

    Ali Akbar Tahaei

    2014-01-01

    Full Text Available Auditory processing deficits have been hypothesized as an underlying mechanism for stuttering. Previous studies have demonstrated abnormal responses in subjects with persistent developmental stuttering (PDS at the higher level of the central auditory system using speech stimuli. Recently, the potential usefulness of speech evoked auditory brainstem responses in central auditory processing disorders has been emphasized. The current study used the speech evoked ABR to investigate the hypothesis that subjects with PDS have specific auditory perceptual dysfunction. Objectives. To determine whether brainstem responses to speech stimuli differ between PDS subjects and normal fluent speakers. Methods. Twenty-five subjects with PDS participated in this study. The speech-ABRs were elicited by the 5-formant synthesized syllable/da/, with duration of 40 ms. Results. There were significant group differences for the onset and offset transient peaks. Subjects with PDS had longer latencies for the onset and offset peaks relative to the control group. Conclusions. Subjects with PDS showed a deficient neural timing in the early stages of the auditory pathway consistent with temporal processing deficits and their abnormal timing may underlie to their disfluency.

  4. In Vitro Endothelialization Test of Biomaterials Using Immortalized Endothelial Cells.

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    Ken Kono

    Full Text Available Functionalizing biomaterials with peptides or polymers that enhance recruitment of endothelial cells (ECs can reduce blood coagulation and thrombosis. To assess endothelialization of materials in vitro, primary ECs are generally used, although the characteristics of these cells vary among the donors and change with time in culture. Recently, primary cell lines immortalized by transduction of simian vacuolating virus 40 large T antigen or human telomerase reverse transcriptase have been developed. To determine whether immortalized ECs can substitute for primary ECs in material testing, we investigated endothelialization on biocompatible polymers using three lots of primary human umbilical vein endothelial cells (HUVEC and immortalized microvascular ECs, TIME-GFP. Attachment to and growth on polymer surfaces were comparable between cell types, but results were more consistent with TIME-GFP. Our findings indicate that TIME-GFP is more suitable for in vitro endothelialization testing of biomaterials.

  5. Endothelial RIG-I activation impairs endothelial function.

    Science.gov (United States)

    Asdonk, Tobias; Motz, Inga; Werner, Nikos; Coch, Christoph; Barchet, Winfried; Hartmann, Gunther; Nickenig, Georg; Zimmer, Sebastian

    2012-03-30

    Endothelial dysfunction is a crucial part of the chronic inflammatory atherosclerotic process and is mediated by innate and acquired immune mechanisms. Recent studies suggest that pattern recognition receptors (PRR) specialized in immunorecognition of nucleic acids may play an important role in endothelial biology in a proatherogenic manner. Here, we analyzed the impact of endothelial retinoic acid inducible gene I (RIG-I) activation upon vascular endothelial biology. Wild type mice were injected intravenously with 32.5 μg of the RIG-ligand 3pRNA (RNA with triphosphate at the 5'end) or polyA control every other day for 7 days. In 3pRNA-treated mice, endothelium-depended vasodilation was significantly impaired, vascular oxidative stress significantly increased and circulating endothelial microparticle (EMP) numbers significantly elevated compared to controls. To gain further insight in RIG-I dependent endothelial biology, cultured human coronary endothelial cells (HCAEC) and endothelial progenitor cells (EPC) were stimulated in vitro with 3pRNA. Both cells types express RIG-I and react with receptor upregulation upon stimulation. Reactive oxygen species (ROS) formation is enhanced in both cell types, whereas apoptosis and proliferation is not significantly affected in HCAEC. Importantly, HCAEC release significant amounts of proinflammatory cytokines in response to RIG-I stimulation. This study shows that activation of the cytoplasmatic nucleic acid receptor RIG-I leads to endothelial dysfunction. RIG-I induced endothelial damage could therefore be an important pathway in atherogenesis. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. [Medical significance of endothelial glycocalyx].

    Science.gov (United States)

    Frati-Munari, Alberto C

    2013-01-01

    Endothelial glycocalyx is a layer composed by glycosaminoglycans, proteoglycans and glycoproteins attached to the vascular endothelial luminal surface. It has several physiological roles: shear stress mechanotransduction to the endothelial cells, regulation of fluids and macromolecules vascular permeability, of coagulation cascade activation and fibrinolysis, and protects the endothelium from platelets and leukocytes adhesion. In general, glycocalyx protects vascular wall against pathogenic insults. The glycocalyx may be damaged by abnormal shear stress, reactive oxygen species, hypernatremia, hyperglycemia, hypercholesterolemia and inflammatory molecules, resulting in endothelial dysfunction, enhanced vascular permeability, lipoproteins leakage to subendothelial space, activation of plasma coagulation, and increased adherence of platelets and leukocytes to the endothelial cells. Shredding of glycocalyx appears as an important initial step in the pathophysiology of vascular diseases. Copyright © 2012 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

  7. Resting Heart Rate and Auditory Evoked Potential

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    Simone Fiuza Regaçone

    2015-01-01

    Full Text Available The objective of this study was to evaluate the association between rest heart rate (HR and the components of the auditory evoked-related potentials (ERPs at rest in women. We investigated 21 healthy female university students between 18 and 24 years old. We performed complete audiological evaluation and measurement of heart rate for 10 minutes at rest (heart rate monitor Polar RS800CX and performed ERPs analysis (discrepancy in frequency and duration. There was a moderate negative correlation of the N1 and P3a with rest HR and a strong positive correlation of the P2 and N2 components with rest HR. Larger components of the ERP are associated with higher rest HR.

  8. Visual evoked potentials in rubber factory workers.

    Science.gov (United States)

    Tandon, O P; Kumar, V

    1997-01-01

    Pattern reversal visual evoked potentials (pVEP) were studied in 39 male rubber factory workers in the age range of 18-55 years and 20 control subjects (aged 18-46 years) not exposed to the rubber factory environment. Results revealed that 20 (51%) rubber factory workers had abnormal latencies of wave P1 (dominant component of pVEP) as per accepted criteria of 99% tolerance limit set for the control group (i.e. any value above mean +3 SD of control was considered abnormal). The section-wise per cent distribution of abnormalities was vulcanization (83%), tubing (75%), calendering (60%), loading (38%) and mixing (14%). This study provides electrophysiological evidence that rubber factory environments affect the conduction processes in optical pathways from their origin in the retina to striate cortex. However, this study has its limitations in not identifying the specific chemical(s) causing these changes in VEP.

  9. Bayesian analysis of MEG visual evoked responses

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, D.M.; George, J.S.; Wood, C.C.

    1999-04-01

    The authors developed a method for analyzing neural electromagnetic data that allows probabilistic inferences to be drawn about regions of activation. The method involves the generation of a large number of possible solutions which both fir the data and prior expectations about the nature of probable solutions made explicit by a Bayesian formalism. In addition, they have introduced a model for the current distributions that produce MEG and (EEG) data that allows extended regions of activity, and can easily incorporate prior information such as anatomical constraints from MRI. To evaluate the feasibility and utility of the Bayesian approach with actual data, they analyzed MEG data from a visual evoked response experiment. They compared Bayesian analyses of MEG responses to visual stimuli in the left and right visual fields, in order to examine the sensitivity of the method to detect known features of human visual cortex organization. They also examined the changing pattern of cortical activation as a function of time.

  10. Music evokes vicarious emotions in listeners

    Science.gov (United States)

    Kawakami, Ai; Furukawa, Kiyoshi; Okanoya, Kazuo

    2014-01-01

    Why do we listen to sad music? We seek to answer this question using a psychological approach. It is possible to distinguish perceived emotions from those that are experienced. Therefore, we hypothesized that, although sad music is perceived as sad, listeners actually feel (experience) pleasant emotions concurrent with sadness. This hypothesis was supported, which led us to question whether sadness in the context of art is truly an unpleasant emotion. While experiencing sadness may be unpleasant, it may also be somewhat pleasant when experienced in the context of art, for example, when listening to sad music. We consider musically evoked emotion vicarious, as we are not threatened when we experience it, in the way that we can be during the course of experiencing emotion in daily life. When we listen to sad music, we experience vicarious sadness. In this review, we propose two sides to sadness by suggesting vicarious emotion. PMID:24910621

  11. RECORDING OF VESTIBULAR EVOKED MYOGENIC POTENTIALS

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    A. A. Sazgar

    2006-05-01

    Full Text Available It has been shown recently that loud clicks evoke myogenic potentials in the tonically contracting sternocleidomastoid muscles. Studies have suggested that these potentials are of vestibular origin, especially of the saccule and inferior vestibular nerve. A pilot study was undertaken in our hospital to record vestibular evoked myogenic potentials (VEMP for the first time in Iran. Eighteen healthy volunteers (32 ears without history of otologic or vestibular disorders were subjected to the VEMP test. Twenty-one patients (26 ears with unilateral (6 patients and bilateral (5 patients high frequency sensorineural hearing loss with unknown etiology, acoustic neuroma (1 patient, Meniere’s disease (4 patients and unilateral low frequency sensorineural hearing loss without vestibular complaint (5 patients were also enrolled in this study. VEMP response to clicks was obtained from 84.4% of ears of healthy subjects. These subjects demonstrated short latency waves to click stimuli during tonic neck flexor activation. Mean latencies of first positive (p13 and first negative (n23 potentials in healthy subjects were 12.45 ± 1.9 ms and 20.8 ± 3.5 ms, respectively. Median latencies of these two potentials were 12.1 and 19.3 ms, respectively. We could record VEMP in 5 patients with unilateral and all patients with high and low frequency sensorineural hearing loss without vestibular complaint. In the patient with acoustic neuroma VEMP was absent on the affected side. This technique may offer a new method to evaluate otolith and sacculocollic pathways in human.

  12. Simultaneously estimating the task-related and stimulus-evoked components of hemodynamic imaging measurements.

    Science.gov (United States)

    Herman, Max Charles; Cardoso, Mariana M B; Lima, Bruss; Sirotin, Yevgeniy B; Das, Aniruddha

    2017-07-01

    Task-related hemodynamic responses contribute prominently to functional magnetic resonance imaging (fMRI) recordings. They reflect behaviorally important brain states, such as arousal and attention, and can dominate stimulus-evoked responses, yet they remain poorly understood. To help characterize these responses, we present a method for parametrically estimating both stimulus-evoked and task-related components of hemodynamic responses from subjects engaged in temporally predictable tasks. The stimulus-evoked component is modeled by convolving a hemodynamic response function (HRF) kernel with spiking. The task-related component is modeled by convolving a Fourier-series task-related function (TRF) kernel with task timing. We fit this model with simultaneous electrode recordings and intrinsic-signal optical imaging from the primary visual cortex of alert, task-engaged monkeys. With high [Formula: see text], the model returns HRFs that are consistent across experiments and recording sites for a given animal and TRFs that entrain to task timing independent of stimulation or local spiking. When the task schedule conflicts with that of stimulation, the TRF remains locked to the task emphasizing its behavioral origins. The current approach is strikingly more robust to fluctuations than earlier ones and gives consistently, if modestly, better fits. This approach could help parse the distinct components of fMRI recordings made in the context of a task.

  13. A sensory feedback system for prosthetic hand based on evoked tactile sensation.

    Science.gov (United States)

    Liu, X X; Chai, G H; Qu, H E; Lan, N

    2015-01-01

    The lack of reliable sensory feedback has been one of the barriers in prosthetic hand development. Restoring sensory function from prosthetic hand to amputee remains a great challenge to neural engineering. In this paper, we present the development of a sensory feedback system based on the phenomenon of evoked tactile sensation (ETS) at the stump skin of residual limb induced by transcutaneous electrical nerve stimulation (TENS). The system could map a dynamic pattern of stimuli to an electrode placed on the corresponding projected finger areas on the stump skin. A pressure transducer placed at the tip of prosthetic fingers was used to sense contact pressure, and a high performance DSP processor sampled pressure signals, and calculated the amplitude of feedback stimulation in real-time. Biphasic and charge-balanced current pulses with amplitude modulation generated by a multi-channel laboratory stimulator were delivered to activate sensory nerves beneath the skin. We tested this sensory feedback system in amputee subjects. Preliminary results showed that the subjects could perceive different levels of pressure at the tip of prosthetic finger through evoked tactile sensation (ETS) with distinct grades and modalities. We demonstrated the feasibility to restore the perceptual sensation from prosthetic fingers to amputee based on the phenomenon of evoked tactile sensation (ETS) with TENS.

  14. Endothelial plasticity governs the site-specific leukocyte recruitment in hepatocellular cancer.

    Science.gov (United States)

    Salnikova, Olga; Breuhahn, Kai; Hartmann, Natalie; Schmidt, Jan; Ryschich, Eduard

    2013-11-15

    The correct programming of the endothelial cell phenotype is crucial for efficient leukocyte recruitment to tumor tissue. It has been previously described that T cells infiltrated hepatocellular cancer (HCC) tissue mainly in peritumoral, stromal and tumor border areas. In the current study, phenotype features of tumor endothelial cells and their potential impact on leukocyte recruitment were analyzed in murine tissue of HCC. In the murine model, proinflammatory stimulation with IL-1β induced leukocyte recruitment in the blood vessels of peripheral tumor areas and in nonmalignant liver tissue, but not in deeper tumor blood vessels. Furthermore, peripheral tumor endothelium, but not deeper tumor blood vessels exhibited a "normalized" hepatic sinusoidal endothelial cell (HSEC)-like phenotype with regard to the expression of adhesion molecules and liver sinusoidal endothelial markers. When tumor endothelial cells were isolated and incubated in vitro, their phenotype rapidly changed and became almost identical to normal hepatic endothelial cells. Interestingly, cytokine production in HCC was strongly dysregulated as compared to normal liver, with IL-1RN exhibiting the most prominent elevation. Experiments with isolated hepatic endothelial cells showed that IL-1RN effectively antagonized the activating action of IL-1β on the expression of adhesion molecules and T cell attachment. These novel insights indicate that tumor endothelium of HCC represents a plastic system that is susceptible to microenvironmental changes. The peritumoral and tumor border areas have distinct endothelial cell phenotype, which promotes leukocyte recruitment to HCC tissue. Copyright © 2013 UICC.

  15. Sex differences in pudendal somatosensory evoked potentials.

    Science.gov (United States)

    Pelliccioni, G; Piloni, V; Sabbatini, D; Fioravanti, P; Scarpino, O

    2014-06-01

    Somatosensory evoked potentials (SEPs) of the pudendal nerve are a well-established diagnostic tool for the evaluation of pelvic floor disorders. However, the possible influence of sex differences on response latencies has not been established yet. The aim of this study was to standardize the procedures and to evaluate possible effects of gender differences on anal and penile/clitoral SEPs. The anal and dorsal penile/clitoral SEPs were recorded in 84 healthy subjects (40 males and 44 females; mean age 47.9 ± 16.6 years, range 16-81 years; mean height 168.3 ± 20.3 cm, range 155-187 cm). Pudendal SEPs were evoked with a bipolar surface electrode stimulating the clitoris or the base of the penis and the anal orifice and recorded using scalp electrodes. The latency of the first positive component (P1) was measured. The effect and possible interaction of (a) stimulation site and (b) gender on the two variables was explored by multivariate analysis of variance (MANOVA). The examination was well tolerated and a reproducible waveform of sufficient quality was obtained in all the subjects examined. In the female subjects, a mean cortical P1 latency of 37.0 ± 2.6 and 36.4 ± 3.2 ms for anal and clitoral stimulation, respectively, was found. In the male subjects, the cortical latencies were 38.0 ± 3.5 ms for the anal stimulation and 40.2 ± 3.7 ms for the penile stimulation. At MANOVA, a statistically significant main effect of stimulation site and gender as well as a significant interaction between the two variables was found. Anal and dorsal penile/clitoral SEPs represent a well-tolerated and reproducible method to assess the functional integrity of the sensory pathways in male and female subjects. Obtaining sex-specific reference data, by individual electrophysiological testing, is highly recommended because of significant latency differences between males and females, at least as far as penile/clitoral responses are concerned.

  16. Lifestyle factors and endothelial function.

    Science.gov (United States)

    Papageorgiou, Nikolaos; Tousoulis, Dimitris; Androulakis, Emmanuel; Giotakis, Aris; Siasos, Gerasimos; Latsios, George; Stefanadis, Christodoulos

    2012-01-01

    Atherosclerotic disease remains a major health problem around the world. The central role of endothelium and inflammation in all stages of the atherosclerotic process is advocated by significant data. Moreover, clinical evidence supports the prognostic potential of endothelial dysfunction for the development of ischemic events and for adverse outcome after acute coronary syndromes. Interestingly, suboptimal lifestyle choices are implicated in the development and deterioration of this endothelial dysfunction, a fact with significant impact, considering the contribution of endothelial dysfunction in atherosclerosis and its complications. Many epidemiological research studies, using a variety of strategies, provide encouraging evidence suggesting that lifestyle modifications may have significant impact regarding the improvement of endothelial function. However, little is known about how individual's genetic background interacts with environmental influences on vascular health, thereby making the interpretation of the relative importance of lifestyle interventions more complicated.

  17. Visually evoked spiking evolves while spontaneous ongoing dynamics persist

    Directory of Open Access Journals (Sweden)

    Raoul eHuys

    2016-01-01

    Full Text Available Neurons in the primary visual cortex spontaneously spike even when there are no visual stimuli. It is unknown whether the spiking evoked by visual stimuli is just a modification of the spontaneous ongoing cortical spiking dynamics or whether the spontaneous spiking state disappears and is replaced by evoked spiking. This study of laminar recordings of spontaneous spiking and visually evoked spiking of neurons in the ferret primary visual cortex shows that the spiking dynamics does not change: the spontaneous spiking as well as evoked spiking is controlled by a stable and persisting fixed point attractor. Its existence guarantees that evoked spiking return to the spontaneous state. However, the spontaneous ongoing spiking state and the visual evoked spiking states are qualitatively different and are separated by a threshold (separatrix. The functional advantage of this organization is that it avoids the need for a system reorganization following visual stimulation, and impedes the transition of spontaneous spiking to evoked spiking and the propagation of spontaneous spiking from layer 4 to layers 2-3.

  18. Evoked otoacoustic emissions behaviour in retinitis pigmentosa.

    Science.gov (United States)

    Fiore, C; Cagini, C; Menduno, P; Toniassoni, I; Desantis, A; Pennacchi, A; Ricci, G; Molini, E

    1994-01-01

    The hearing function was studied in 26 patients affected by retinitis pigmentosa (RP) and in their relatives. Sixteen patients showed bilateral normal hearing when examined with traditional audiometric methods. In these normoacusic patients evoked otoacoustic emissions (EOE) have been studied. The EOE offer a unique opportunity to measure objectively the function of outer hair cells: they record the amplitude of the energy produced by the outer hair cells of the coclea following an acoustic stimulation. The data have been statistically compared, using the Student's t-test, with those obtained in a homogeneous control-group of normal subjects. In normoacusic subjects with RP the average values of EOE intensity are statistically lower than those of normal subjects in 64 of the 127 frequency bands examined. Moreover, the distribution of the EOE in patients with retinitis pigmentosa proved to be more discontinous than that observed in the normal subjects. The EOE recorded in 14 normoacusic relatives show in some cases small anomalies but the data, on account of the limited sample group, cannot be statistically evaluated. Therefore a subclinical alteration of the Organ of Corti is found in 100% of the patients affected by RP, although they appear to be normoacusic to usual audiometric tests.

  19. Transient evoked otoacoustic emissions in rock musicians.

    Science.gov (United States)

    Høydal, Erik Harry; Lein Størmer, Carl Christian; Laukli, Einar; Stenklev, Niels Christian

    2017-09-01

    Our focus in this study was the assessment of transient evoked otoacoustic emissions (TEOAEs) in a large group of rock musicians. A further objective was to analyse tinnitus among rock musicians as related to TEOAEs. The study was a cross-sectional survey of rock musicians selected at random. A control group was included at random for comparison. We recruited 111 musicians and a control group of 40 non-musicians. Testing was conducted by using clinical examination, pure tone audiometry, TEOAEs and a questionnaire. TEOAE SNR in the half-octave frequency band centred on 4 kHz was significantly lower bilaterally in musicians than controls. This effect was strongly predicted by age and pure-tone hearing threshold levels in the 3-6 kHz range. Bilateral hearing thresholds were significantly higher at 6 kHz in musicians. Twenty percent of the musicians had permanent tinnitus. There was no association between the TEOAE parameters and permanent tinnitus. Our results suggest an incipient hearing loss at 6 kHz in rock musicians. Loss of TEOAE SNR in the 4 kHz half-octave frequency band was observed, but it was related to higher mean 3-6 kHz hearing thresholds and age. A large proportion of rock musicians have permanent tinnitus.

  20. Visual evoked potential study in slow learners.

    Science.gov (United States)

    Khaliq, Farah; Anjana, Yumnam; Vaney, Neelam

    2009-01-01

    Slow learners are individuals with low achievement and comparably low IQ scores. It may be a symptom reflecting a larger underlying problem in them. Sensory neural processing of visual information can be one of the contributory factors for their underachievement. The present study was undertaken to examine the integrity and function of visual pathway by means of Visual Evoked Potential (VEP). Pattern reversal VEP was performed on seventeen slow learners. Fifteen age and sex matched children with good school performance and normal IQ were taken as controls. There was significant prolongation of N75 component of VEP in slow learners. The latencies of P100 and N145 were also increased but could not reach the level of significance. Our findings are suggestive of the presence of a weaker VEP response in slow learners indicative of a deficit early in the visual processing. There is some abnormality in the geniculate afferents to V1 which is consistent with a defect in the magnocellular pathway at the level of Visual Area 1 or earlier.

  1. Speech-evoked cortical auditory responses in children with normal hearing

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    Aseel Almeqbel

    2013-12-01

    Full Text Available Objective: Cortical auditory-evoked potentials (CAEPs, an objective measure of human speech encoding in individuals with normal or impaired auditory systems, can be used to assess the outcomes of hearing aids and cochlear implants in infants, or in young children who cannot co-operate for behavioural speech discrimination testing. The current study aimed to determine whether naturally produced speech stimuli /m/, /g/ and /t/ evoke distinct CAEP response patterns that can be reliably recorded and differentiated, based on their spectral information and whether the CAEP could be an electrophysiological measure to differentiate between these speech sounds.Method: CAEPs were recorded from 18 school-aged children with normal hearing, tested in two groups: younger (5 - 7 years and older children (8 - 12 years. Cortical responses differed in their P1 and N2 latencies and amplitudes in response to /m/, /g/ and /t/ sounds (from low-, mid- and high-frequency regions, respectively. The largest amplitude of the P1 and N2 component was for /g/ and the smallest was for /t/. The P1 latency in both age groups did not show any significant difference between these speech sounds. The N2 latency showed a significant change in the younger group but not in the older group. The N2 latency of the speech sound /g/ was always noted earlier in both groups.Conclusion: This study demonstrates that spectrally different speech sounds are encoded differentially at the cortical level, and evoke distinct CAEP response patterns. CAEP latencies and amplitudes may provide an objective indication that spectrally different speech sounds are encoded differently at the cortical level.

  2. Light evokes melanopsin-dependent vocalization and neural activation associated with aversive experience in neonatal mice.

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    Anton Delwig

    Full Text Available Melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs are the only functional photoreceptive cells in the eye of newborn mice. Through postnatal day 9, in the absence of functional rods and cones, these ipRGCs mediate a robust avoidance behavior to a light source, termed negative phototaxis. To determine whether this behavior is associated with an aversive experience in neonatal mice, we characterized light-induced vocalizations and patterns of neuronal activation in regions of the brain involved in the processing of aversive and painful stimuli. Light evoked distinct melanopsin-dependent ultrasonic vocalizations identical to those emitted under stressful conditions, such as isolation from the litter. In contrast, light did not evoke the broad-spectrum calls elicited by acute mechanical pain. Using markers of neuronal activation, we found that light induced the immediate-early gene product Fos in the posterior thalamus, a brain region associated with the enhancement of responses to mechanical stimulation of the dura by light, and thought to be the basis for migrainous photophobia. Additionally, light induced the phosphorylation of extracellular-related kinase (pERK in neurons of the central amygdala, an intracellular signal associated with the processing of the aversive aspects of pain. However, light did not activate Fos expression in the spinal trigeminal nucleus caudalis, the primary receptive field for painful stimulation to the head. We conclude that these light-evoked vocalizations and the distinct pattern of brain activation in neonatal mice are consistent with a melanopsin-dependent neural pathway involved in processing light as an aversive but not acutely painful stimulus.

  3. Evoked potentials and head injury. 1. Rating of evoked potential abnormality.

    Science.gov (United States)

    Rappaport, M; Hall, K; Hopkins, H K; Belleza, T

    1981-10-01

    This paper describes a method for rating the degree of abnormality of auditory, visual and somatosensory evoked potential patterns in head injury (HI) patients. Criteria for judging degree of EP abnormality are presented that allow assessment of the extent and severity of subcortical and cortical dysfunction associated with traumatic brain damage. Interrater reliability data based upon blind ratings of normal and HI patients are presented and shown to be highly significant. Tables of normative values of peak latencies and amplitudes are given and illustrations of EP patterns of different degrees of abnormality are presented.

  4. Disciplinary Distinction or Responsibility?

    Science.gov (United States)

    Rogers, Priscilla S.

    1996-01-01

    Argues that some of the disciplinary distinctions proposed in the lead articles of this special issue actually represent aspects of theory or practice that are fundamental to all four fields. Examines what is deemphasized to suggest where attention may be needed--in particular, disciplinary relationships with organizations and disciplinary…

  5. Endothelial-regenerating cells: an expanding universe.

    Science.gov (United States)

    Steinmetz, Martin; Nickenig, Georg; Werner, Nikos

    2010-03-01

    Atherosclerosis is the most common cause for cardiovascular diseases and is based on endothelial dysfunction. A growing body of evidence suggests the contribution of bone marrow-derived endothelial progenitor cells, monocytic cells, and mature endothelial cells to vessel formation and endothelial rejuvenation. To this day, various subsets of these endothelial-regenerating cells have been identified according to cellular origin, phenotype, and properties in vivo and in vitro. However, the definition and biology, especially of endothelial progenitor cells, is complex and under heavy debate. In this review, we focus on current definitions of endothelial progenitor cells, highlight the clinical relevance of endothelial-regenerating cells, and provide new insights into cell-cell interactions involved in endothelial cell rejuvenation.

  6. Nanofiber density determines endothelial cell behavior on hydrogel matrix

    Energy Technology Data Exchange (ETDEWEB)

    Berti, Fernanda V., E-mail: fernanda@intelab.ufsc.br [Department of Chemical and Food Engineering, Federal University of Santa Catarina, 88040-900 Florianópolis, SC (Brazil); Rambo, Carlos R. [Department of Electrical Engineering, Federal University of Santa Catarina, 88040-900 Florianópolis, SC (Brazil); Dias, Paulo F. [Department of Cell Biology, Embryology and Genetics, Federal University of Santa Catarina, 88040-900 Florianópolis, SC (Brazil); Porto, Luismar M. [Department of Chemical and Food Engineering, Federal University of Santa Catarina, 88040-900 Florianópolis, SC (Brazil)

    2013-12-01

    When cultured under static conditions, bacterial cellulose pellicles, by the nature of the polymer synthesis that involves molecular oxygen, are characterized by two distinct surface sides. The upper surface is denser in fibers (entangled) than the lower surface that shows greater surface porosity. Human umbilical vein endothelial cells (HUVECs) were used to exploit how the microarchitecture (i.e., surface porosity, fiber network structure, surface topology, and fiber density) of bacterial cellulose pellicle surfaces influence cell–biomaterial interaction and therefore cell behavior. Adhesion, cell ingrowth, proliferation, viability and cell death mechanisms were evaluated on the two pellicle surface sides. Cell behavior, including secondary necrosis, is influenced only by the microarchitecture of the surface, since the biomaterial is extremely pure (constituted of cellulose and water only). Cell–cellulose fiber interaction is the determinant signal in the cell–biomaterial responses, isolated from other frequently present interferences such as protein and other chemical traces usually present in cell culture matrices. Our results suggest that microarchitecture of hydrogel materials might determine the performance of biomedical products, such as bacterial cellulose tissue engineering constructs (BCTECs). - Highlights: • Topography of BC pellicle is relevant to determine endothelial cells' fate. • Cell–biomaterial response is affected by the topography of BC-pellicle surface. • Endothelial cells exhibit different behavior depending on the BC topography. • Apoptosis and necrosis of endothelial cells were affected by the BC topography.

  7. Towards a neural basis of music-evoked emotions.

    Science.gov (United States)

    Koelsch, Stefan

    2010-03-01

    Music is capable of evoking exceptionally strong emotions and of reliably affecting the mood of individuals. Functional neuroimaging and lesion studies show that music-evoked emotions can modulate activity in virtually all limbic and paralimbic brain structures. These structures are crucially involved in the initiation, generation, detection, maintenance, regulation and termination of emotions that have survival value for the individual and the species. Therefore, at least some music-evoked emotions involve the very core of evolutionarily adaptive neuroaffective mechanisms. Because dysfunctions in these structures are related to emotional disorders, a better understanding of music-evoked emotions and their neural correlates can lead to a more systematic and effective use of music in therapy. Copyright 2010 Elsevier Ltd. All rights reserved.

  8. Distraction Reduces Both Early and Late Electrocutaneous Stimulus Evoked Potentials

    NARCIS (Netherlands)

    Blom, J.H.G.; Wiering, Caro H.; van der Lubbe, Robert Henricus Johannes

    2012-01-01

    Previous electroencephalography studies revealed mixed effects of sustained distraction on early negative and later positive event-related potential components evoked by electrocutaneous stimuli. In our study we further examined the influence of sustained distraction to clarify these discrepancies.

  9. Click-evoked responses in vestibular afferents in rats

    National Research Council Canada - National Science Library

    Zhu, Hong; Tang, Xuehui; Wei, Wei; Mustain, William; Xu, Youguo; Zhou, Wu

    2011-01-01

    Sound activates not only the cochlea but also the vestibular end organs. Research on this phenomenon led to the discovery of the sound-evoked vestibular myogenic potentials recorded from the sternocleidomastoid muscles...

  10. Vasculogenesis, angiogenesis and the molecular organisation of endothelial junctions in the early human placenta.

    Science.gov (United States)

    Leach, Lopa; Babawale, Michael O; Anderson, Mark; Lammiman, Michael

    2002-01-01

    Vasculogenesis and angiogenesis are regulated by the capacity of endothelial cells to adhere to each other and form new tubes. The presence and role of junctional adhesion molecules during physiological vasculogenesis is unknown. Using ultrastructural and immunocytochemical approaches, we compared the junctional phenotype of developing vessels of the first-trimester human placenta with vessels in the last trimester; the latter include newly formed terminal capillaries and the quiescent vascular bed. First-trimester placental vessels contained the adherens junctional molecules, vascular endothelial cadherin and alpha- and beta-catenin but lacked plakoglobin, the component of fully differentiated adherens junctions. Furthermore, these vessels did not contain the transmembrane tight junctional molecules occludin and claudin-1 and -2. This profile reflects the phenotype of terminal capillaries but differs from large vessels of the full-term placenta. Electron microscopic studies revealed that endothelial tight junctions are present in the first-trimester placenta. Thus, occludin and claudin-1 appear to play no part in the formation of endothelial tight junctions, but are a later requirement. In the early placenta, the predominant growth factor appears to be vascular endothelial growth factor (VEGF), whilst at term, angiopoietin-1 was present in large vessels, with intense angiopoietin-2 immunofluorescence (and VEGF) located in terminal villous capillaries. Thus, endothelial junctions in the human placenta possess two distinct molecular phenotypes, i.e. stable or dynamic, dependent on maturity and plasticity. These distinct phenotypes may be influenced by the angiopoietins/VEGF present in the placenta. Copyright 2002 S. Karger AG, Basel

  11. Bubble-Induced Endothelial Microparticles Promote Endothelial Dysfunction.

    Science.gov (United States)

    Yu, Xuhua; Xu, Jiajun; Huang, Guoyang; Zhang, Kun; Qing, Long; Liu, Wenwu; Xu, Weigang

    2017-01-01

    Decompression sickness is a systemic pathophysiological process caused by bubbles and endothelial microparticles (EMPs) are established markers reflecting competency of endothelial function and vascular biology. Here, we investigated the effects of bubble-induced EMPs on endothelial cells in vitro and vivo. Rat pulmonary microvascular endothelial cells (PMVECs) were isolated and stimulated by bubbles and bubble-induced EMPs were collected and incubated with normal PMVECs in vitro. Cell viability and apoptosis were detected using Cell Counting Kit-8 assay and Annexin V FITC/PI double staining, respectively. Cell permeability and pro-inflammatory cytokines were determined by electric cell substrate impedance sensing and enzyme-linked immunosorbent assay, respectively. Intracellular nitric oxide and reactive oxygen species production were analyzed microscopically. In vivo study, bubble-induced EMPs were intravenously injected to the rats and soluble thrombomodulin, intercellular adhesion molecule 1, and vascullar adhesion molecule 1 were involved in evaluating endothelial dysfunction. In our study, bubble stimulus resulted in a significant increase of EMPs release by 3 fold. Bubble-induced EMPs significantly decreased cell viability and increased cell apoptosis. Moreover, bubble-induced EMPs induced abnormal increase of cell permeability and over-expression of pro-inflammatory cytokines. Intracellular ROS production increased while NO production decreased. These negative effects caused by bubble-induced EMPs were remarkably suppressed when EMPs pretreated with surfactant FSN-100. Finally, intravenous injection of bubble-induced EMPs caused elevations of soluble thrombomodulin and pro-inflammatory cytokines in the circulation. Altogether, our results demonstrated that bubble-induced EMPs can mediate endothelial dysfunction in vitro and vivo, which can be attenuated by EMPs abatement strategy. These data expanded our horizon of the detrimental effects of bubble

  12. Bubble-Induced Endothelial Microparticles Promote Endothelial Dysfunction.

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    Xuhua Yu

    Full Text Available Decompression sickness is a systemic pathophysiological process caused by bubbles and endothelial microparticles (EMPs are established markers reflecting competency of endothelial function and vascular biology. Here, we investigated the effects of bubble-induced EMPs on endothelial cells in vitro and vivo. Rat pulmonary microvascular endothelial cells (PMVECs were isolated and stimulated by bubbles and bubble-induced EMPs were collected and incubated with normal PMVECs in vitro. Cell viability and apoptosis were detected using Cell Counting Kit-8 assay and Annexin V FITC/PI double staining, respectively. Cell permeability and pro-inflammatory cytokines were determined by electric cell substrate impedance sensing and enzyme-linked immunosorbent assay, respectively. Intracellular nitric oxide and reactive oxygen species production were analyzed microscopically. In vivo study, bubble-induced EMPs were intravenously injected to the rats and soluble thrombomodulin, intercellular adhesion molecule 1, and vascullar adhesion molecule 1 were involved in evaluating endothelial dysfunction. In our study, bubble stimulus resulted in a significant increase of EMPs release by 3 fold. Bubble-induced EMPs significantly decreased cell viability and increased cell apoptosis. Moreover, bubble-induced EMPs induced abnormal increase of cell permeability and over-expression of pro-inflammatory cytokines. Intracellular ROS production increased while NO production decreased. These negative effects caused by bubble-induced EMPs were remarkably suppressed when EMPs pretreated with surfactant FSN-100. Finally, intravenous injection of bubble-induced EMPs caused elevations of soluble thrombomodulin and pro-inflammatory cytokines in the circulation. Altogether, our results demonstrated that bubble-induced EMPs can mediate endothelial dysfunction in vitro and vivo, which can be attenuated by EMPs abatement strategy. These data expanded our horizon of the detrimental effects

  13. Estetrol modulates endothelial nitric oxide synthesis in human endothelial cells

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    Maria Magdalena eMontt-Guevara

    2015-07-01

    Full Text Available Estetrol (E4 is a natural human estrogen that is present at high concentrations during pregnancy. E4 has been reported to act as an endogenous estrogen receptor modulator, exerting estrogenic actions on the endometrium or the central nervous system but presenting antagonistic effects on the breast. Due to these characteristics, E4 is currently being developed for a number of clinical applications, including contraception and menopausal hormone therapy. Endothelial nitric oxide (NO is a key player for vascular function and disease during pregnancy and throughout ageing in women. Endothelial NO is an established target of estrogens that enhance its formation in human endothelial cells. We here addressed the effects of E4 on the activity and expression of the endothelial nitric oxide synthase (eNOS in cultured human umbilical vein endothelial cells (HUVEC. E4 stimulated the activation of eNOS and NO secretion in HUVEC. E4 was significantly less effective compared to E2 and a peculiar concentration-dependent effect was found, with higher amounts of E4 being less effective than lower concentrations. When E2 was combined with E4, an interesting pattern was noted. E4 antagonized NO synthesis induced by pregnancy-like E2 concentrations. However, E4 did not impede the modest induction of NO synthesis associated with postmenopausal-like E2 levels. These results support the hypothesis that E4 may be a regulator of NO synthesis in endothelial cells and raise questions on its peculiar signaling in this context. Our results may be useful to interpret the role of E4 during human pregnancy and possibly to help develop this interesting steroid for clinical use.

  14. Endothelial cells, fibroblasts and vasculitis.

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    Buckley, Christopher D; Rainger, G Ed; Nash, Gerard B; Raza, Karim

    2005-07-01

    One of the most important questions in vasculitis research is not why inflammation of blood vessels occurs but why it persists, often in a site-specific manner. In this review we illustrate how stromal cells, such as fibroblasts and pericytes, might play an important role in regulating the site at which vasculitis occurs. Smooth muscle cells and fibroblasts directly influence the behaviour of overlying vascular cells, amplifying the response of the endothelium to proinflammatory agents such as TNF-alpha and allowing enhanced and inappropriate leucocyte recruitment. An abnormal local vascular stromal environment can therefore influence local endothelial function and drive the persistence of local vascular inflammation. However, such local vascular inflammation can have distant effects on the systemic vascular system, leading to widespread endothelial cell dysfunction. Vascular endothelial dysfunction is common in a range of immune-mediated inflammatory diseases, is seen in multiple vascular beds, and is reversible following the induction of disease remission. The mechanisms that drive such systemic vascular endothelial dysfunction are unclear but factors such as TNF-alpha and CRP may play a role. Persistence of such widespread endothelial dysfunction in systemic vasculitis appears to have long-term consequences, leading to the acceleration of atherosclerosis and premature ischaemic heart disease. It may also underlie the accelerated atherosclerosis seen in other immune-mediated rheumatic diseases, such as rheumatoid arthritis.

  15. Inhibition of TGF-β signaling enables human corneal endothelial cell expansion in vitro for use in regenerative medicine.

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    Naoki Okumura

    Full Text Available Corneal endothelial dysfunctions occurring in patients with Fuchs' endothelial corneal dystrophy, pseudoexfoliation syndrome, corneal endotheliitis, and surgically induced corneal endothelial damage cause blindness due to the loss of endothelial function that maintains corneal transparency. Transplantation of cultivated corneal endothelial cells (CECs has been researched to repair endothelial dysfunction in animal models, though the in vitro expansion of human CECs (HCECs is a pivotal practical issue. In this study we established an optimum condition for the cultivation of HCECs. When exposed to culture conditions, both primate and human CECs showed two distinct phenotypes: contact-inhibited polygonal monolayer and fibroblastic phenotypes. The use of SB431542, a selective inhibitor of the transforming growth factor-beta (TGF-β receptor, counteracted the fibroblastic phenotypes to the normal contact-inhibited monolayer, and these polygonal cells maintained endothelial physiological functions. Expression of ZO-1 and Na(+/K(+-ATPase maintained their subcellular localization at the plasma membrane. Furthermore, expression of type I collagen and fibronectin was greatly reduced. This present study may prove to be the substantial protocol to provide the efficient in vitro expansion of HCECs with an inhibitor to the TGF-β receptor, and may ultimately provide clinicians with a new therapeutic modality in regenerative medicine for the treatment of corneal endothelial dysfunctions.

  16. Flash visual evoked potentials in preterm infants.

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    Feng, Jing-Jing; Wang, Wei-Ping; Guo, Shu-Juan; Liu, Zhi-Wei; Xu, Xiu

    2013-03-01

    To describe the development of flash visual evoked potentials (FVEPs) in preterm infants from 1 to 18 months and to determine if the maturation of FVEPs is similar to that of term infants. Longitudinal follow-up study. Twenty very low birth weight (VLBW) preterm infants, 42 low birth weight (LBW) preterm infants, and 41 term infants underwent FVEP recordings and neurodevelopmental examinations at 1, 3, 6, 9, 12, and 18 months of corrected and chronological ages. The FVEP recordings were carried out with the VikingQuest-IV neuroelectrophysiological device (VikingQuest, Nicolet, WI), and neurodevelopmental assessments were made by the Development Screen Test and Bayley Scales of Infant Development, Second Edition. At 1, 3, 6, and 9 months of age, neurodevelopment was measured with the Mental Index and Developmental Quotient. At 12 and 18 months, neurodevelopment was assessed using the Mental Developmental Index and Psychomotor Developmental Index. Two FVEP values were analyzed: the P2 amplitude (peak to peak from the preceding N2 wave) and the latency of the P2 wave. There was no significant difference for age-dependent decreased pattern of FVEP P2 latency between preterm infants and the control group. This pattern consisted of a rapid decrease in the first 6 months of life, a gradual decline from 6 to 12 months of age, and a steady reduction from 12 to 18 months of age. The P2 latencies were prolonged significantly at all 6 recorded times in the VLBW group compared with the controls and showed a delay in the LBW group at 1 and 3 months of corrected age. The maturation of P2 latency in LBW infants is similar to that of the controls at 3 months of corrected age, but the maturation of P2 latency in VLBW children remained delayed when compared with the controls until 18 months of corrected age. Although the FVEP development pattern of preterm infants was similar to that of healthy full-term infants, the former had deficits in visual electrophysiologic maturation

  17. Parallel pathways from whisker and visual sensory cortices to distinct frontal regions of mouse neocortex.

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    Sreenivasan, Varun; Kyriakatos, Alexandros; Mateo, Celine; Jaeger, Dieter; Petersen, Carl C H

    2017-07-01

    The spatial organization of mouse frontal cortex is poorly understood. Here, we used voltage-sensitive dye to image electrical activity in the dorsal cortex of awake head-restrained mice. Whisker-deflection evoked the earliest sensory response in a localized region of primary somatosensory cortex and visual stimulation evoked the earliest responses in a localized region of primary visual cortex. Over the next milliseconds, the initial sensory response spread within the respective primary sensory cortex and into the surrounding higher order sensory cortices. In addition, secondary hotspots in the frontal cortex were evoked by whisker and visual stimulation, with the frontal hotspot for whisker deflection being more anterior and lateral compared to the frontal hotspot evoked by visual stimulation. Investigating axonal projections, we found that the somatosensory whisker cortex and the visual cortex directly innervated frontal cortex, with visual cortex axons innervating a region medial and posterior to the innervation from somatosensory cortex, consistent with the location of sensory responses in frontal cortex. In turn, the axonal outputs of these two frontal cortical areas innervate distinct regions of striatum, superior colliculus, and brainstem. Sensory input, therefore, appears to map onto modality-specific regions of frontal cortex, perhaps participating in distinct sensorimotor transformations, and directing distinct motor outputs.

  18. ActRIIA and BMPRII Type II BMP receptor subunits selectively required for Smad4-independent BMP7-evoked chemotaxis.

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    Jeanette C Perron

    2009-12-01

    Full Text Available Bone morphogenetic protein (BMP-evoked reorientation and chemotaxis of cells occurs with rapid onset and involves events local to the cell membrane. The signaling pathways underlying these rapid processes likely diverge from those mediating classical transcriptional responses to BMPs but it remains unclear how BMP receptors are utilized to generate distinct intracellular mechanisms. We show that BMP7-evoked chemotaxis of monocytic cells depends on the activity of canonical type II BMP receptors. Although the three canonical type II BMP receptors are expressed in monocytic cells, inhibition of receptor subunit expression by RNAi reveals that ActRIIA and BMPRII, but not ActRIIB, are each essential for BMP7-evoked chemotaxis but not required individually for BMP-mediated induction. Furthermore, the chemotactic response to BMP7 does not involve canonical Smad4-dependent signaling but acts through PI3K-dependent signaling, illustrating selective activation of distinct intracellular events through differential engagement of receptors. We suggest a model of a BMP receptor complex in which the coordinated activity of ActRIIA and BMPRII receptor subunits selectively mediates the chemotactic response to BMP7.

  19. Endothelial function in vasovagal syncope.

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    Pietrucha, Artur Z

    2014-12-01

    Vasovagal syncope (VVS) is a common form of fainting. The pathophysiology of VVS is complex and involves changes in the autonomic and vascular tone, resulting in reflex bradycardia with marked hypotension. Paradoxical peripheral vasodilation caused by endothelial dysfunction may also play a key role in inappropriate hypotension during VVS. Endothelial hyperactivity due to up regulation of nitric oxide synthase leads to profound vasodilation, much stronger than vasodilation caused by adrenergic stimulation in response to orthostatic stress alone. Studies have reported significantly higher flow-mediated dilation and higher plasma nitric oxide concentration in people with vasovagal syndrome. Patients with VVS showed decreased vasoconstrictive agent endothelin-1 levels during orthostatic stress. Coagulation and fibrinolysis activity also play important roles in endothelial function in syncopal patients. The response of the endothelium to orthostatic stress is similar to the reaction to haemorrhagic stress and is likely to be a remnant from the evolutionary adaptation of primates.

  20. Endothelial keratoplasty: evolution and horizons

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    Gustavo Teixeira Grottone

    2012-12-01

    Full Text Available Endothelial keratoplasty has been adopted by corneal surgeons worldwide as an alternative to penetrating keratoplasty (PK in the treatment of corneal endothelial disorders. Since the first surgeries in 1998, different surgical techniques have been used to replace the diseased endothelium. Compared with penetrating keratoplasty, all these techniques may provide faster and better visual rehabilitation with minimal change in refractive power of the transplanted cornea, minimal induced astigmatism, elimination of suture-induced complications and late wound dehiscence, and a reduced demand for postoperative care. Translational research involving cell-based therapy is the next step in work on endothelial keratoplasty. The present review updates information on comparisons among different techniques and predicts the direction of future treatment.

  1. Independent control of gamma and theta activity by distinct interneuron networks in the olfactory bulb.

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    Fukunaga, Izumi; Herb, Jan T; Kollo, Mihaly; Boyden, Edward S; Schaefer, Andreas T

    2014-09-01

    Circuits in the brain possess the ability to orchestrate activities on different timescales, but the manner in which distinct circuits interact to sculpt diverse rhythms remains unresolved. The olfactory bulb is a classic example of a place in which slow theta and fast gamma rhythms coexist. Furthermore, inhibitory interneurons that are generally implicated in rhythm generation are segregated into distinct layers, neatly separating local and global motifs. We combined intracellular recordings in vivo with circuit-specific optogenetic interference to examine the contribution of inhibition to rhythmic activity in the mouse olfactory bulb. We found that the two inhibitory circuits controlled rhythms on distinct timescales: local, glomerular networks coordinated theta activity, regulating baseline and odor-evoked inhibition, whereas granule cells orchestrated gamma synchrony and spike timing. Notably, granule cells did not contribute to baseline rhythms or sniff-coupled odor-evoked inhibition. Thus, activities on theta and gamma timescales are controlled by separate, dissociable inhibitory networks in the olfactory bulb.

  2. The paradox of music-evoked sadness: an online survey.

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    Taruffi, Liila; Koelsch, Stefan

    2014-01-01

    This study explores listeners' experience of music-evoked sadness. Sadness is typically assumed to be undesirable and is therefore usually avoided in everyday life. Yet the question remains: Why do people seek and appreciate sadness in music? We present findings from an online survey with both Western and Eastern participants (N = 772). The survey investigates the rewarding aspects of music-evoked sadness, as well as the relative contribution of listener characteristics and situational factors to the appreciation of sad music. The survey also examines the different principles through which sadness is evoked by music, and their interaction with personality traits. Results show 4 different rewards of music-evoked sadness: reward of imagination, emotion regulation, empathy, and no "real-life" implications. Moreover, appreciation of sad music follows a mood-congruent fashion and is greater among individuals with high empathy and low emotional stability. Surprisingly, nostalgia rather than sadness is the most frequent emotion evoked by sad music. Correspondingly, memory was rated as the most important principle through which sadness is evoked. Finally, the trait empathy contributes to the evocation of sadness via contagion, appraisal, and by engaging social functions. The present findings indicate that emotional responses to sad music are multifaceted, are modulated by empathy, and are linked with a multidimensional experience of pleasure. These results were corroborated by a follow-up survey on happy music, which indicated differences between the emotional experiences resulting from listening to sad versus happy music. This is the first comprehensive survey of music-evoked sadness, revealing that listening to sad music can lead to beneficial emotional effects such as regulation of negative emotion and mood as well as consolation. Such beneficial emotional effects constitute the prime motivations for engaging with sad music in everyday life.

  3. The paradox of music-evoked sadness: an online survey.

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    Liila Taruffi

    Full Text Available This study explores listeners' experience of music-evoked sadness. Sadness is typically assumed to be undesirable and is therefore usually avoided in everyday life. Yet the question remains: Why do people seek and appreciate sadness in music? We present findings from an online survey with both Western and Eastern participants (N = 772. The survey investigates the rewarding aspects of music-evoked sadness, as well as the relative contribution of listener characteristics and situational factors to the appreciation of sad music. The survey also examines the different principles through which sadness is evoked by music, and their interaction with personality traits. Results show 4 different rewards of music-evoked sadness: reward of imagination, emotion regulation, empathy, and no "real-life" implications. Moreover, appreciation of sad music follows a mood-congruent fashion and is greater among individuals with high empathy and low emotional stability. Surprisingly, nostalgia rather than sadness is the most frequent emotion evoked by sad music. Correspondingly, memory was rated as the most important principle through which sadness is evoked. Finally, the trait empathy contributes to the evocation of sadness via contagion, appraisal, and by engaging social functions. The present findings indicate that emotional responses to sad music are multifaceted, are modulated by empathy, and are linked with a multidimensional experience of pleasure. These results were corroborated by a follow-up survey on happy music, which indicated differences between the emotional experiences resulting from listening to sad versus happy music. This is the first comprehensive survey of music-evoked sadness, revealing that listening to sad music can lead to beneficial emotional effects such as regulation of negative emotion and mood as well as consolation. Such beneficial emotional effects constitute the prime motivations for engaging with sad music in everyday life.

  4. The Paradox of Music-Evoked Sadness: An Online Survey

    Science.gov (United States)

    Taruffi, Liila; Koelsch, Stefan

    2014-01-01

    This study explores listeners’ experience of music-evoked sadness. Sadness is typically assumed to be undesirable and is therefore usually avoided in everyday life. Yet the question remains: Why do people seek and appreciate sadness in music? We present findings from an online survey with both Western and Eastern participants (N = 772). The survey investigates the rewarding aspects of music-evoked sadness, as well as the relative contribution of listener characteristics and situational factors to the appreciation of sad music. The survey also examines the different principles through which sadness is evoked by music, and their interaction with personality traits. Results show 4 different rewards of music-evoked sadness: reward of imagination, emotion regulation, empathy, and no “real-life” implications. Moreover, appreciation of sad music follows a mood-congruent fashion and is greater among individuals with high empathy and low emotional stability. Surprisingly, nostalgia rather than sadness is the most frequent emotion evoked by sad music. Correspondingly, memory was rated as the most important principle through which sadness is evoked. Finally, the trait empathy contributes to the evocation of sadness via contagion, appraisal, and by engaging social functions. The present findings indicate that emotional responses to sad music are multifaceted, are modulated by empathy, and are linked with a multidimensional experience of pleasure. These results were corroborated by a follow-up survey on happy music, which indicated differences between the emotional experiences resulting from listening to sad versus happy music. This is the first comprehensive survey of music-evoked sadness, revealing that listening to sad music can lead to beneficial emotional effects such as regulation of negative emotion and mood as well as consolation. Such beneficial emotional effects constitute the prime motivations for engaging with sad music in everyday life. PMID:25330315

  5. A novel approach to prevent endothelial hyperpermeability: the Crataegus extract WS® 1442 targets the cAMP/Rap1 pathway.

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    Bubik, Martin F; Willer, Elisabeth A; Bihari, Peter; Jürgenliemk, Guido; Ammer, Hermann; Krombach, Fritz; Zahler, Stefan; Vollmar, Angelika M; Fürst, Robert

    2012-01-01

    Endothelial hyperpermeability followed by edema formation is a hallmark of many severe disorders. Effective drugs directly targeting endothelial barrier function are widely lacking. We hypothesized that the hawthorn (Crataegus spp.) extract WS® 1442, a proven multi-component drug against moderate forms of heart failure, would prevent vascular leakage by affecting endothelial barrier-regulating systems. In vivo, WS® 1442 inhibited the histamine-evoked extravasation of FITC-dextran from mouse cremaster muscle venules. In cultured human endothelial cells, WS® 1442 blocked the thrombin-induced FITC-dextran permeability. By applying biochemical and microscopic techniques, we revealed that WS® 1442 abrogates detrimental effects of thrombin on adherens junctions (vascular endothelial-cadherin), the F-actin cytoskeleton, and the contractile apparatus (myosin light chain). Mechanistically, WS® 1442 inhibited the thrombin-induced rise of intracellular calcium (ratiometric measurement), followed by an inactivation of PKC and RhoA (pulldown assay). Moreover, WS® 1442 increased endothelial cAMP levels (ELISA), which consequently activated PKA and Rap1 (pulldown assay). Utilizing pharmacological inhibitors or siRNA, we found that PKA is not involved in barrier protection, whereas Epac1, Rap1, and Rac1 play a crucial role in the WS® 1442-induced activation of cortactin, which triggers a strong cortical actin rearrangement. In summary, WS® 1442 effectively protects against endothelial barrier dysfunction in vitro and in vivo. It specifically interacts with endothelial permeability-regulating systems by blocking the Ca(2+)/PKC/RhoA and activating the cAMP/Epac1/Rap1 pathway. As a proven safe herbal drug, WS® 1442 opens a novel pharmacological approach to treat hyperpermeability-associated diseases. This in-depth mechanistic work contributes to a better acceptance of this herbal remedy. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Gene expression analysis of embryonic stem cells expressing VE-cadherin (CD144 during endothelial differentiation

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    Libermann Towia

    2008-05-01

    Full Text Available Abstract Background Endothelial differentiation occurs during normal vascular development in the developing embryo. This process is recapitulated in the adult when endothelial progenitor cells are generated in the bone marrow and can contribute to vascular repair or angiogenesis at sites of vascular injury or ischemia. The molecular mechanisms of endothelial differentiation remain incompletely understood. Novel approaches are needed to identify the factors that regulate endothelial differentiation. Methods Mouse embryonic stem (ES cells were used to further define the molecular mechanisms of endothelial differentiation. By flow cytometry a population of VEGF-R2 positive cells was identified as early as 2.5 days after differentiation of ES cells, and a subset of VEGF-R2+ cells, that were CD41 positive at 3.5 days. A separate population of VEGF-R2+ stem cells expressing the endothelial-specific marker CD144 (VE-cadherin was also identified at this same time point. Channels lined by VE-cadherin positive cells developed within the embryoid bodies (EBs formed by differentiating ES cells. VE-cadherin and CD41 expressing cells differentiate in close proximity to each other within the EBs, supporting the concept of a common origin for cells of hematopoietic and endothelial lineages. Results Microarray analysis of >45,000 transcripts was performed on RNA obtained from cells expressing VEGF-R2+, CD41+, and CD144+ and VEGF-R2-, CD41-, and CD144-. All microarray experiments were performed in duplicate using RNA obtained from independent experiments, for each subset of cells. Expression profiling confirmed the role of several genes involved in hematopoiesis, and identified several putative genes involved in endothelial differentiation. Conclusion The isolation of CD144+ cells during ES cell differentiation from embryoid bodies provides an excellent model system and method for identifying genes that are expressed during endothelial differentiation and that

  7. Hypotonic shock stimulates ascorbate release from coronary artery endothelial cells by a Ca2+ -independent pathway.

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    Davis, Kim A; Samson, Sue E; Wilson, John X; Grover, Ashok K

    2006-10-24

    In endothelial cells, anion channels open upon osmotic swelling during shear stress and hypotonic shock. Therefore, we examined the effects of hypotonic shock on release of the antioxidant anion ascorbate from pig coronary artery endothelial cells. Hypotonic shock potentiated ascorbate release from freshly isolated or cultured pig coronary artery endothelial cells; subsequently cultured endothelial cells were used. The hypotonic shock-induced increase in Asc release was rapid, depended on the degree of hypotonic shock, and not due to membrane leakiness. Stimulating P2Y2 like receptors in endothelial cells with ATP causes ascorbate release via a Ca2+ -mediated pathway. Hypotonic shock-induced release differed from the Ca2+-mediated Asc release because: (a) the increase in release with hypotonic shock was additive to that with ATP or A23187 (Ca2+ -ionophore), (b) apyrase, suramin or removing extracellular Ca2+ did not affect the hypotonic shock-stimulated release, (c) anion channel blockers inhibited the release by the two pathways differently, and (d) hypotonic shock increased the ascorbate release from endothelial cells and cultured smooth muscle cells whereas the Ca2+ -mediated ascorbate release occurred only in endothelial cells. Accumulation of ascorbate by endothelial cells was examined at extracellular ascorbate concentrations of 10 (Na+ -ascorbate symporter not saturated) and 5000 microM (Na+ -ascorbate symporter saturated). Hypotonic shock and A23187 decreased ascorbate accumulation at 10 microM ascorbate but increased it at 5000 microM. The effects of the two treatments were additive and also differed from each other with substitution of gluconate for extracellular chloride. Thus, ascorbate release from endothelial cells can be potentiated by two distinct pathways - hypotonic shock mediated and ATP/Ca2+ stimulated.

  8. Optical and electrical recording of neural activity evoked by graded contrast visual stimulus

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    Bulf Luca

    2007-07-01

    Full Text Available Abstract Background Brain activity has been investigated by several methods with different principles, notably optical ones. Each method may offer information on distinct physiological or pathological aspects of brain function. The ideal instrument to measure brain activity should include complementary techniques and integrate the resultant information. As a "low cost" approach towards this objective, we combined the well-grounded electroencephalography technique with the newer near infrared spectroscopy methods to investigate human visual function. Methods The article describes an embedded instrumentation combining a continuous-wave near-infrared spectroscopy system and an electroencephalography system to simultaneously monitor functional hemodynamics and electrical activity. Near infrared spectroscopy (NIRS signal depends on the light absorption spectra of haemoglobin and measures the blood volume and blood oxygenation regulation supporting the neural activity. The NIRS and visual evoked potential (VEP are concurrently acquired during steady state visual stimulation, at 8 Hz, with a b/w "windmill" pattern, in nine human subjects. The pattern contrast is varied (1%, 10%, 100% according to a stimulation protocol. Results In this study, we present the measuring system; the results consist in concurrent recordings of hemodynamic changes and evoked potential responses emerging from different contrast levels of a patterned stimulus. The concentration of [HbO2] increases and [HHb] decreases after the onset of the stimulus. Their variation shows a clear relationship with the contrast value: large contrast produce huge difference in concentration, while low contrast provokes small concentration difference. This behaviour is similar to the already known relationship between VEP response amplitude and contrast. Conclusion The simultaneous recording and analysis of NIRS and VEP signals in humans during visual stimulation with a b/w pattern at variable

  9. Tumor-endothelium cross talk blocks recruitment of neutrophils to endothelial cells: a novel mechanism of endothelial cell anergy.

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    Blaheta, Roman A; Powerski, Maciej; Hudak, Lukasz; Juengel, Eva; Jonas, Dietger; von Knethen, Andreas; Doerr, Hans Willhelm; Cinatl, Jindrich

    2009-10-01

    Tumor cells have evolved effective strategies to escape the host immune response. The objective of this study was to determine whether tumor cells can condition endothelial cells in a specific manner to prevent subsequent adhesion of polymorphonuclear neutrophils (PMNs) and/or peripheral blood lymphocytes (PBLs). Human umbilical vein endothelial cells (HUVECs) and UKF-NB-4 neuroblastoma tumor cells were established in coculture on opposite sides of porous transwell filters. After 24 hours with and without HUVEC conditioning, PMNs or PBLs were added to the HUVEC monolayer. Adhesion to conditioned HUVEC versus adhesion to nonconditioned HUVEC was compared. Effects on endothelial CD44v4, CD44v5, CD44v7, intercellular adhesion molecule 1 (ICAM-1), E-selectin, and vascular cell adhesion molecule 1 (VCAM-1) adhesion receptor expression were analyzed by flow cytometry, intracellular signaling proteins of the mitogen-activated protein kinase pathway and protein kinase C (PKC) subtypes quantified by Western blot analysis. Endothelial conditioning led to a distinct reduction in PMN but not in PBL adhesion to HUVEC. CD44 was significantly reduced, whereas ICAM-1, E-selectin, and VCAM-1 were not altered during HUVEC conditioning. Antibody blockade against CD44v4, CD44v5, and CD44v7 inhibited PMN but not PBL binding. The observed effects were caused by direct tumor cell-HUVEC contact because addition of isolated tumor cell membrane fragments but not of soluble cell culture supernatant to HUVEC induced the CD44 receptor loss. PKCalpha activity was strongly enhanced in conditioned HUVEC. Blocking PKC prevented the reduction in PMN binding, indicating that this protein is involved in PMN adhesion regulation. A novel tumor escape strategy is presented here. Cell contact-dependent adhesion of tumor cells to the vascular wall promotes down-regulation of endothelial CD44 receptor expression, impairing an effective neutrophil attack.

  10. Tumor-Endothelium Cross Talk Blocks Recruitment of Neutrophils to Endothelial Cells: A Novel Mechanism of Endothelial Cell Anergy

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    Roman A. Blaheta

    2009-10-01

    Full Text Available Tumor cells have evolved effective strategies to escape the host immune response. The objective of this study was to determine whether tumor cells can condition endothelial cells in a specific manner to prevent subsequent adhesion of polymorphonuclear neutrophils (PMNs and/or peripheral blood lymphocytes (PBLs. Human umbilical vein endothelial cells (HUVECs and UKF-NB-4 neuroblastoma tumor cells were established in coculture on opposite sides of porous transwell filters. After 24 hours with and without HUVEC conditioning, PMNs or PBLs were added to the HUVEC monolayer. Adhesion to conditioned HUVEC versus adhesion to nonconditioned HUVEC was compared. Effects on endothelial CD44v4, CD44v5, CD44v7, intercellular adhesion molecule 1 (ICAM-1, E-selectin, and vascular cell adhesion molecule 1 (VCAM-1 adhesion receptor expression were analyzed by flow cytometry, intracellular signaling proteins of the mitogen-activated protein kinase pathway and protein kinase C (PKC subtypes quantified by Western blot analysis. Endothelial conditioning led to a distinct reduction in PMN but not in PBL adhesion to HUVEC. CD44 was significantly reduced, whereas ICAM-1, E-selectin, and VCAM-1 were not altered during HUVEC conditioning. Antibody blockade against CD44v4, CD44v5, and CD44v7 inhibited PMN but not PBL binding. The observed effects were caused by direct tumor cell-HUVEC contact because addition of isolated tumor cell membrane fragments but not of soluble cell culture supernatant to HUVEC induced the CD44 receptor loss. PKCα activity was strongly enhanced in conditioned HUVEC. Blocking PKC prevented the reduction in PMN binding, indicating that this protein is involved in PMN adhesion regulation. A novel tumor escape strategy is presented here. Cell contact-dependent adhesion of tumor cells to the vascular wall promotes down-regulation of endothelial CD44 receptor expression, impairing an effective neutrophil attack.

  11. Amiodarone reduces depolarization-evoked glutamate release from hippocampual synaptosomes

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    Chia Yu Chang

    2017-03-01

    Full Text Available Decreased brain glutamate level has emerged as a new therapeutic approach for epilepsy. This study investigated the effect and mechanism of amiodarone, an anti-arrhythmic drug with antiepileptic activity, on glutamate release in the rat hippocampus. In a synaptosomal preparation, amiodarone reduced 4-aminopyridine-evoked Ca2+-dependent glutamate release and cytosolic Ca2+ concentration elevation. Amiodarone did not affect the 4-aminopyridine-evoked depolarization of the synaptosomal membrane potential or the Na+ channel activator veratridine-evoked glutamate release, indicating that the amiodarone-mediated inhibition of glutamate release is not caused by a decrease in synaptosomal excitability. The inhibitory effect of amiodarone on 4-aminopyridine-evoked glutamate release was markedly decreased in synaptosomes pretreated with the Cav2.2 (N-type and Cav2.1 (P/Q-type channel blocker ω-conotoxin MVIIC, the calmodulin antagonists W7 and calmidazolium, or the protein kinase A inhibitors H89 and KT5720. However, the intracellular Ca2+-release inhibitors dantrolene and CGP37157 had no effect on the amiodarone-mediated inhibition of glutamate release. Furthermore, amiodarone reduced the frequency of miniature excitatory postsynaptic currents without affecting their amplitude in hippocampal slices. Our data suggest that amiodarone reduces Ca2+ influx through N- and P/Q-type Ca2+ channels, subsequently reducing the Ca2+-calmodulin/protein kinase A cascade to inhibit the evoked glutamate release from rat hippocampal nerve terminals.

  12. Endothelial keratoplasty versus penetrating keratoplasty for Fuchs endothelial dystrophy.

    Science.gov (United States)

    Nanavaty, Mayank A; Wang, Xue; Shortt, Alex J

    2014-02-14

    Fuchs endothelial dystrophy (FED) is a condition in which there is premature degeneration of corneal endothelial cells. When the number of endothelial cells is reduced to a significant degree, fluid begins to accumulate within the cornea. As a result, the cornea loses its transparency and the individual suffers a reduction in vision. The only successful surgical treatment for this condition is replacement of part or all of the cornea with healthy tissue from a donor. The established procedure, penetrating keratoplasty (PKP), has been used for many years and its safety and efficacy are well known. Endothelial keratoplasty (EK) techniques are relatively new surgical procedures and their safety and efficacy relative to PKP are uncertain. The objective of this review was to compare the benefits and complications related to two surgical methods (EK and PKP) of replacing the diseased endothelial layer of the cornea with a healthy layer in people with FED. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2014, Issue 1), MEDLINE (January 1950 to January 2014), EMBASE (January 1980 to January 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to January 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) and ClinicalTrials.gov (www.clinicaltrials.gov). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 27 January 2014. We included all randomised controlled trials (RCTs) comparing EK versus PKP for people (of any age and gender) who had been clinically diagnosed with FED. Two authors independently screened the search results, assessed trial quality and extracted data using the standard methodological procedures expected by The Cochrane Collaboration. We included three RCTs that enrolled a total of 139 eyes of 136 participants and analysed 123 (88%) eyes. Two RCTs

  13. Evaluation of Endothelial Dysfunction In Vivo.

    Science.gov (United States)

    Todiras, Mihail; Alenina, Natalia; Bader, Michael

    2017-01-01

    Vascular endothelial cells play a major role in maintaining cardiovascular homeostasis. Impairment of physiological properties of the endothelium, such as the promotion of vasodilation and anti-aggregation, leads to a condition called endothelial dysfunction. Endothelial dysfunction is an important early event in the pathogenesis of atherosclerosis and has been shown to have prognostic value in predicting vascular events including stroke and myocardial infarction.Endothelial-dependent vasodilation is one of the most widely used methods for assessment of endothelial function in rodents. It includes pharmacological stimulation (for example by acetylcholine) of endothelial release of NO and other vasoactive compounds in comparison with vascular response to endothelium-independent dilators such as sodium nitroprusside. However, usually this technique is performed in anesthetized animals. Here we describe a method which allows evaluation of endothelial dysfunction in conscious, freely moving mice and rats.

  14. Endothelial dysfunction: a comprehensive appraisal

    Directory of Open Access Journals (Sweden)

    Vilariño Jorge O

    2006-02-01

    Full Text Available Abstract The endothelium is a thin monocelular layer that covers all the inner surface of the blood vessels, separating the circulating blood from the tissues. It is not an inactive organ, quite the opposite. It works as a receptor-efector organ and responds to each physical or chemical stimulus with the release of the correct substance with which it may maintain vasomotor balance and vascular-tissue homeostasis. It has the property of producing, independently, both agonistic and antagonistic substances that help to keep homeostasis and its function is not only autocrine, but also paracrine and endocrine. In this way it modulates the vascular smooth muscle cells producing relaxation or contraction, and therefore vasodilatation or vasoconstriction. The endothelium regulating homeostasis by controlling the production of prothrombotic and antithrombotic components, and fibrynolitics and antifibrynolitics. Also intervenes in cell proliferation and migration, in leukocyte adhesion and activation and in immunological and inflammatory processes. Cardiovascular risk factors cause oxidative stress that alters the endothelial cells capacity and leads to the so called endothelial "dysfunction" reducing its capacity to maintain homeostasis and leads to the development of pathological inflammatory processes and vascular disease. There are different techniques to evaluate the endothelium functional capacity, that depend on the amount of NO produced and the vasodilatation effect. The percentage of vasodilatation with respect to the basal value represents the endothelial functional capacity. Taking into account that shear stress is one of the most important stimulants for the synthesis and release of NO, the non-invasive technique most often used is the transient flow-modulate "endothelium-dependent" post-ischemic vasodilatation, performed on conductance arteries such as the brachial, radial or femoral arteries. This vasodilatation is compared with the

  15. The Effects of kisspeptin-10 on Migration and Proliferation of Endothelial Cell

    Directory of Open Access Journals (Sweden)

    Fatemeh Golzar

    2015-01-01

    Full Text Available Background: Migration, expansion and survival of endothelial cells that are an important cellular component of blood vessels plays an important role in the induction of tumor growth. Kisspeptins (kp, peptides that bind to coupled-G protein receptor (GPR54, inhibit each step of metastatic cascade include invasion, migration and homing, angiogenesis, survival and proliferation. In this study we investigated effects of kisspeptin-10, the most potent member of kisspeptin family, on Migration and proliferation of endothelial cells that are necessary for angiogenesis and tumor metastasis. Materials and Methods: We compared migration of Human Umbilical Vein Endothelial Cells (HUVECs were treated with 10-100 or 500 nM kp-10 for 24 hours and no treated cells using an in vitro trans membrane migration assay and HUVEC proliferation of treated endothelial cells with 10-100 or 500 nM kp-10 for 48 hours and no treated cells was measured by MTT Cell Proliferation Assay Kit. Analysis of data was performed using the Kruskal-Wallis test followed by the Mann-Whitney test. Results: Migration and proliferation of endothelial cells were increased at lower concentration of kp-10 specially at 100 nM while higher concentration reduced both migration and proliferation. Conclusion: Our data showed that different concentrations of kp-10 have distinct effects on migration and proliferation of endothelial cells.

  16. Endothelial progenitor cell subsets and preeclampsia: Findings and controversies

    Directory of Open Access Journals (Sweden)

    Armin Attar

    2017-10-01

    Full Text Available Vascular remodeling is an essential component of gestation. Endothelial progenitor cells (EPCs play an important role in the regulation of vascular homeostasis. The results of studies measuring the number of EPCs in normal pregnancies and in preeclampsia have been highly controversial or even contradictory because of some variations in technical issues and different methodologies enumerating three distinct subsets of EPCs: circulating angiogenic cells (CAC, colony forming unit endothelial cells (CFU-ECs, and endothelial colony-forming cells (ECFCs. In general, most studies have shown an increase in the number of CACs in the maternal circulation with a progression in the gestational age in normal pregnancies, while functional capacities measured by CFU-ECs and ECFCs remain intact. In the case of preeclampsia, mobilization of CACs and ECFCs occurs in the peripheral blood of pregnant women, but the functional capacities shown by culture of the derived colony-forming assays (CFU-EC and ECFC assays are altered. Furthermore, the number of all EPC subsets will be reduced in umbilical cord blood in the case of preeclampsia. As EPCs play an important role in the homeostasis of vascular networks, the difference in their frequency and functionality in normal pregnancies and those with preeclampsia can be expected. In this review, there was an attempt to provide a justification for these controversies.

  17. Challenges in pediatric endothelial keratoplasty

    Directory of Open Access Journals (Sweden)

    Vikas Mittal

    2014-01-01

    Full Text Available We performed endothelial keratoplasty (EK in three eyes of two siblings (2.5 years, male and 3.5 years, female with congenital hereditary endothelial dystrophy (CHED and report the intraoperative and postoperative difficulties. Repeated iris prolapse, apprehension of crystalline lens touch due to positive vitreous pressure, and need for frequent air injections to attach the graft were intraoperative challenges in all three eyes. These were addressed by use of Sheet′s glide instead of Busin′s glide during graft insertion and suturing of main and side ports before air injection. One eye had graft dislocation on second postoperative day due to eye rubbing by the child. Graft was repositioned with air and a venting incision was created. Postoperative examination required repeated general anesthesia. Corneal edema resolved completely in all three eyes. Present case series highlights the possible intraoperative and postoperative challenges and their solutions in pediatric EK for CHED.

  18. Flow-Mediated Endothelial Mechanotransduction

    Science.gov (United States)

    Davies, Peter F.

    2011-01-01

    Mechanical forces associated with blood flow play important roles in the acute control of vascular tone, the regulation of arterial structure and remodeling, and the localization of atherosclerotic lesions. Major regulation of the blood vessel responses occurs by the action of hemodynamic shear stresses on the endothelium. The transmission of hemodynamic forces throughout the endothelium and the mechanotransduction mechanisms that lead to biophysical, biochemical, and gene regulatory responses of endothelial cells to hemodynamic shear stresses are reviewed. PMID:7624393

  19. Evoked responses to sinusoidally modulated sound in unanaesthetized dogs

    NARCIS (Netherlands)

    Tielen, A.M.; Kamp, A.; Lopes da Silva, F.H.; Reneau, J.P.; Storm van Leeuwen, W.

    1. 1. Responses evoked by sinusoidally amplitude-modulated sound in unanaesthetized dogs have been recorded from inferior colliculus and from auditory cortex structures by means of chronically indwelling stainless steel wire electrodes. 2. 2. Harmonic analysis of the average responses demonstrated

  20. Pattern visual evoked responses in hereditary spastic paraplegia

    Science.gov (United States)

    Livingstone, I R; Mastaglia, F L; Edis, R; Howe, J W

    1981-01-01

    Pattern visual evoked responses were studied in 13 patients from nine families with dominant herditary spastic paraplegia and in seven sporadic cases. The responses were normal in all the dominantly inherited cases but abnormal in three of the seven sporadic cases. PMID:7217977

  1. The role of Magnetic Resonance Imaging and Visual Evoked ...

    African Journals Online (AJOL)

    Introduction: To report our experience in management of patients with optic neuritis. The effects of brain magnetic resonance imaging and visual evoked potential on management were investigated. Methods: This is a four years clinical trial that included patients presenting with first attack of optic neuritis older than 16 years ...

  2. Temporal Tuning Effects in the Visually Evoked Response,

    Science.gov (United States)

    1985-08-01

    Berger (1932) also observed that these brain waves are slowed in states of depressed function such as sleep activity and that they can be blocked by...Ma4cay and Jefferys, 1973). Transient VER’s, polyphasic in form and 200-500 milliseconds in duration, are evoked by stepwise changes in one or more per

  3. Visual evoked potentials in workers with chronic solvent encephalopathy

    NARCIS (Netherlands)

    Verberk, Maarten M.; Brons, Joke T.; Sallé, Herman J. A.

    2004-01-01

    Objectives. Two promising variations of visual evoked potentials (VEPs) were studied in solvent-exposed workers: the effect of a low-contrast stimulus in comparison with the usually applied high contrast, and the ability of pattern-onset VEP to reveal damage to specific visual cortical areas. In

  4. The computation of evoked heart rate and blood pressure

    NARCIS (Netherlands)

    Koers, G.; Mulder, L.J.M.; van der Veen, F.M.

    1999-01-01

    For many years psychophysiologists have been interested in stimulus related changes in heart rate and blood pressure. To represent these evoked heart rate and blood pressure patterns, heart rate and blood pressure data have to be transformed into equidistant time series. This paper presents an

  5. Single-sweep spectral analysis of contact heat evoked potentials

    DEFF Research Database (Denmark)

    Hansen, Tine M; Graversen, Carina; Frøkjaer, Jens B

    2015-01-01

    AIMS: The cortical response to nociceptive thermal stimuli recorded as contact heat evoked potentials (CHEPs) may be altered by morphine. However, previous studies have averaged CHEPs over multiple stimuli, which are confounded by jitter between sweeps. Thus, the aim was to assess single-sweep ch...

  6. The masseteric reflex evoked by tooth and denture tapping.

    Science.gov (United States)

    Brodin, P; Fløystrand, F; Orstavik, J

    1991-07-01

    The characteristics of the masseter reflex evoked by tapping a maxillary incisor were compared with the reflex pattern evoked by tapping a corresponding denture tooth after insertion of an immediate denture. Up to three inhibitory phases (I-1, I-2 and I-3), followed by excitation, were found on an averaged EMG. The tapping force threshold for the early inhibitory phase was lower than for the late phases. The pattern of the reflex was generally the same before and after insertion of the denture, but the threshold values increased. After insertion of the denture, the threshold for I-1 increased from 1 +/- 0.3N to 2.2 +/- 0.4N, the threshold for I-2 increased from 2.4 +/- 0.8N to 3.8 +/- 0.9N, and the threshold for I-3 increased from 5.1 +/- 0.6N to 8.3 +/- 0.9N. The latency period for I-1 also increased from 12.3 +/- 0.5 ms to 13.1 +/- 0.3 ms after insertion of the denture. After relining, the threshold for evoking I-1 decreased from 2.7 +/- 1.2N to 1.2 +/- 0.6N. It was assumed that the mechanoreceptors situated in the mucosa under the denture base could take over the functional role of the periodontal mechanoreceptors for evoking the masseter reflex during tapping, and that these afferents probably had connections to the same interneurones.

  7. Polyphenols in preventing endothelial dysfunction

    Directory of Open Access Journals (Sweden)

    Sylwia Biegańska-Hensoldt

    2017-03-01

    Full Text Available One of the main causes of mortality in developed countries is atherosclerosis. The pathogenesis of atherosclerosis is associated with endothelial dysfunction. Consumption of food rich in natural antioxidants including polyphenols significantly improves endothelial cells functions.Polyphenols have a beneficial effect on the human body and play an important part in protecting the cardiovascular system. Polyphenols present in food have antioxidant, anti-inflammatory, antihypertensive, antithrombotic and antiproliferative properties. Catechins cause an increase in the activity of endothelial nitric oxide synthase (eNOS and increased production of nitric oxide (NO and decrease in blood pressure. Catechins also reduce platelet adhesion, lower the concentration of C-reactive protein and tumor necrosis factor alpha and interleukin-6. Resveratrol inhibits NADPH oxidase expression, increases the expression of eNOS and NO production as well as decreases the expression of proinflammatory cytokines, and also lowers the concentration of the soluble forms of adhesion molecules – sICAM-1 and sVCAM-1 in blood. Quercetin reduces the blood level of low density lipoprotein cholesterol, lowers blood pressure, reduces the concentration of C-reactive protein and F2-isoprostane level. Curcumin has antagonistic activity to homocysteine. Curcumin increases the expression of eNOS and reduces oxidative DNA damage in rat cardiomyocytes. Numerous attempts are taken for improving the bioavailability of polyphenols in order to increase their use in the body.

  8. Comparison of clinical and evoked pain measures in fibromyalgia.

    Science.gov (United States)

    Harris, Richard E; Gracely, Richard H; McLean, Samuel A; Williams, David A; Giesecke, Thorsten; Petzke, Frank; Sen, Ananda; Clauw, Daniel J

    2006-07-01

    Evoked pain measures such as tender point count and dolorimetry are often used to determine tenderness in studies of fibromyalgia (FM). However, these measures frequently do not improve in clinical trials and are known to be influenced by factors other than pain such as distress and expectancy. The purpose of this investigation was to determine whether evoked pain paradigms that present pressure stimuli in a random fashion (eg, Multiple Random Staircase [MRS]) would track with clinical pain improvement in patients with FM better than traditional measures. Sixty-five subjects enrolled in a randomized clinical trial of acupuncture were observed longitudinally. Clinical pain was measured on a 101-point numerical rating scale (NRS) and the Short Form McGill Pain Questionnaire (SF-MPQ), whereas evoked pressure sensitivity was assessed via manual tender point count, dolorimetry, and MRS methods. Improvements in clinical pain and evoked pain were assessed irrespective of group assignment. Improvement was seen in clinical pain during the course of the trial as measured by both NRS (P = .032) and SF-MPQ (P = .001). The MRS was the only evoked pain measure to improve correspondingly with treatment (MRS, P = .001; tender point count and dolorimeter, P > .05). MRS change scores were correlated with changes in NRS pain ratings (P = .003); however, this association was not stronger than tender point or dolorimetry correlations with clinical pain improvement (P > .05). Pain sensitivity as assessed by random paradigms was associated with improvements in clinical FM pain. Sophisticated pain testing paradigms might be responsive to change in clinical trials. Trials in fibromyalgia often use both clinical and experimental methods of pain assessment; however, these two outcomes are often poorly correlated. We explore the relationship between changes in clinical and experimental pain within FM patients. Pressure pain testing that applies stimuli in a random order is associated with

  9. Amiodarone reduces depolarization-evoked glutamate release from hippocampual synaptosomes.

    Science.gov (United States)

    Chang, Chia Yu; Hung, Chi Feng; Huang, Shu Kuei; Kuo, Jinn Rung; Wang, Su Jane

    2017-03-01

    Decreased brain glutamate level has emerged as a new therapeutic approach for epilepsy. This study investigated the effect and mechanism of amiodarone, an anti-arrhythmic drug with antiepileptic activity, on glutamate release in the rat hippocampus. In a synaptosomal preparation, amiodarone reduced 4-aminopyridine-evoked Ca2+-dependent glutamate release and cytosolic Ca2+ concentration elevation. Amiodarone did not affect the 4-aminopyridine-evoked depolarization of the synaptosomal membrane potential or the Na+ channel activator veratridine-evoked glutamate release, indicating that the amiodarone-mediated inhibition of glutamate release is not caused by a decrease in synaptosomal excitability. The inhibitory effect of amiodarone on 4-aminopyridine-evoked glutamate release was markedly decreased in synaptosomes pretreated with the Cav2.2 (N-type) and Cav2.1 (P/Q-type) channel blocker ω-conotoxin MVIIC, the calmodulin antagonists W7 and calmidazolium, or the protein kinase A inhibitors H89 and KT5720. However, the intracellular Ca2+-release inhibitors dantrolene and CGP37157 had no effect on the amiodarone-mediated inhibition of glutamate release. Furthermore, amiodarone reduced the frequency of miniature excitatory postsynaptic currents without affecting their amplitude in hippocampal slices. Our data suggest that amiodarone reduces Ca2+ influx through N- and P/Q-type Ca2+ channels, subsequently reducing the Ca2+-calmodulin/protein kinase A cascade to inhibit the evoked glutamate release from rat hippocampal nerve terminals. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  10. Visual evoked potentials in patients after methanol poisoning.

    Science.gov (United States)

    Urban, Pavel; Zakharov, Sergey; Diblík, Pavel; Pelclová, Daniela; Ridzoň, Petr

    2016-01-01

    We report the results of the visual evoked potentials (VEP) examination in patients after severe poisoning by methanol. The group of 47 patients (38 males and 9 females) was assembled out of persons who survived an outbreak of poisoning by the methanol adulterated alcohol beverages, which happened in the Czech Republic in 2012-2013. The visual evoked potentials examination was performed using monocular checkerboard pattern-reversal stimulation. Two criteria of abnormality were chosen: missing evoked response, and wave P1 latency > 117 ms. Non-parametric statistical methods (median, range, and the median test) were used to analyze factors influencing the VEP abnormality. The visual evoked potential was abnormal in 20 patients (43%), 5 of them had normal visual acuity on the Snellen chart. The VEP abnormality did not correlate significantly with initial serum concentrations of methanol, formic acid or lactate; however, it showed statistically significant inverse relation to the initial serum pH: the subgroup with the abnormal VEP had significantly lower median pH in comparison with the subgroup with the normal VEP (7.16 vs. 7.34, p = 0.04). The abnormality was not related to chronic alcohol abuse. The visual evoked potentials examination appeared sensitive enough to detected even subclinical impairment of the optic system. Metabolic acidosis is likely to be the key factor related to the development of visual damage induced by methanol. The examination performed with a delay of 1-9 months after the poisoning documented the situation relatively early after the event. It is considered as a baseline for the planned long-term follow-up of the patients, which will make it possible to assess the dynamics of the observed changes, their reversibility, and the occurrence of potential late sequelae. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

  11. The Glycoprofile Patterns of Endothelial Cells in Usual Interstitial Pneumonia

    Directory of Open Access Journals (Sweden)

    A Barkhordari

    2014-09-01

    Full Text Available [THIS ARTICLE HAS BEEN RETRACTED FOR DUPLICATE PUBLICATION] Background: The pathological classification of cryptogenic fibrosing alveolitis has been a matter of debate and controversy for histopathologists. Objective: To identify and specify the glycotypes of capillary endothelial cells in usual interstitial pneumonia (UIP compared to those found in normal tissue. Methods: Sections of formalin-fixed, paraffin-embedded blocks from 16 cases of UIP were studied by lectin histochemistry with a panel of 27 biotinylated lectins and an avidin-peroxidase revealing system. Results: High expression of several classes of glycan was seen de novo in capillary endothelial cells from patients with UIP including small complex and bi/tri-antennary bisected complex N-linked sequences bolund by Concanavalin A and erythro-phytohemagglutinin, respectively, GalNAca1 residues bound by Helix pomatia and Maclura pomifera agglutinins, and L-fucosylated derivatives of type II glycan chains recognized by Ulex europaeus agglutinin-I. Glycans bound by agglutinins from Lycopersicon esculentum (β1,4GlcNAc and Wisteria floribunda (GalNAc as well as GlcNAc oligomers bound by Phytolacca americana and succinylated Wheat Germ agglutinin were also seen in the capillary endothelial cells of UIP. In contrast, L-fucosylated derivatives of type I glycan chains were absent in cells from cases of UIP when Anguilla anguilla agglutinin was applied, unlike the situation in normal tissue. Conclusion: These results may indicate existence of two distinct populations of endothelial cell in UIP with markedly different patterns of glycosylation, reflecting a pattern of differentiation and angiogenesis, which is not detectable morphologically.

  12. Cataract surgery after Descemet stripping endothelial keratoplasty

    Directory of Open Access Journals (Sweden)

    Sunita Chaurasia

    2012-01-01

    Full Text Available Management of endothelial dysfunction in phakic patients is sometimes a dilemma for corneal surgeons. Phakic patients with visually significant cataract and endothelial dysfunction are preferably managed by performing combined cataract surgery with endothelial keratoplasty. However, combined surgery may be deferred in eyes with early incipient cataract, younger age and where anterior chamber is poorly visualized. As cataract formation may be accelerated after endothelial keratoplasty, these eyes may need cataract surgery subsequently. Surgical intervention in eyes with endothelial keratoplasty is of concern as this may affect the graft adversely and threaten graft survival. In this report, we describe the intraoperative surgical details and postoperative clinical course of a patient who underwent phacoemulsification with intraocular lens implantation after Descemet stripping automated endothelial keratoplasty (DSAEK.

  13. Endothelial cell loss after autologous rotational keratoplasty.

    Science.gov (United States)

    Birnbaum, Florian; Reinhard, Thomas; Böhringer, Daniel; Sundmacher, Rainer

    2005-01-01

    To investigate whether it may be possible to ascertain the influence of immunological factors on chronic endothelial cell loss by comparing chronic endothelial cell loss after autologous rotational penetrating keratoplasty and after homologous penetrating keratoplasty. For six patients who had undergone autologous rotational penetrating keratoplasty the relative annual loss of endothelial cells was calculated by means of an exponential regression analysis. The findings were compared with those in a homogeneous historical control group (53 patients undergoing homologous penetrating keratoplasty for keratoconus). After autologous rotational keratoplasty relative annual loss of endothelial cells was 1.1%+/-2.6% (mean +/- standard deviation). Relative annual loss of endothelial cells in the control-group was 16.7%+/-20.8%. The results of the study lead to the assumption that immunological influences might be the main cause for chronic endothelial cell loss after homologous penetrating keratoplasty.

  14. Herpes Simplex Virus endotheliitis following descemet‘s membrane endothelial keratoplasty

    Directory of Open Access Journals (Sweden)

    Siamak Zarei-Ghanavati1

    2015-01-01

    Conclusion:HSV endotheliitis may occur in the early postoperative period after DMEK and manifest as endothelial dysfunction leading to donor detachment. Anti-viral medication may help treat the acute phase and reduce the risk of recurrence.

  15. Role of Lipotoxicity in Endothelial Dysfunction

    OpenAIRE

    Kim, Jeong-a; Montagnani, Monica; Chandrasekran, Sruti; Quon, Michael J.

    2012-01-01

    Lipotoxicity, caused in large part by overnutrition, directly leads to endothelial dysfunction. Excess lipids in both the circulation and at the tissue level contribute to endothelial dysfunction that underlies much of the pathophysiology of both metabolic disease, including obesity and diabetes and their CV complications. Direct lipotoxic effects on other organs as well as secondary insults from endothelial dysfunction synergize to cause substantial morbidity and mortality. Lifestyle interve...

  16. Resveratrol: A Multifunctional Compound Improving Endothelial Function

    OpenAIRE

    Li, Huige; F?rstermann, Ulrich

    2009-01-01

    The red wine polyphenol resveratrol boosts endothelium-dependent and -independent vasorelaxations. The improvement of endothelial function by resveratrol is largely attributable to nitric oxide (NO) derived from endothelial NO synthase (eNOS). By stimulating eNOS expression, eNOS phosphorylation and eNOS deacetylation, resveratrol enhances endothelial NO production. By upregulating antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) and suppressing the expression a...

  17. Impairment of IKCa channels contributes to uteroplacental endothelial dysfunction in rat diabetic pregnancy.

    Science.gov (United States)

    Gokina, Natalia I; Bonev, Adrian D; Phillips, Julie; Gokin, Alexander P; Veilleux, Kelsey; Oppenheimer, Karen; Goloman, Gabriela

    2015-08-15

    Diabetes in rat pregnancy is associated with impaired vasodilation of the maternal uteroplacental vasculature. In the present study, we explored the role of endothelial cell (EC) Ca(2+)-activated K(+) channels of small conductance (SKCa channels) and intermediate conductance (IKCa channels) in diabetes-induced uterine vascular dysfunction. Diabetes was induced by injection of streptozotocin to second-day pregnant rats and confirmed by the development of maternal hyperglycemia. Control rats were injected with citrate buffer. Changes in smooth muscle cell intracellular Ca(2+) concentration, membrane potential, and vasodilation induced by SKCa/IKCa channel activators were studied in uteroplacental arteries of control and diabetic rats. The impact of diabetes on SKCa- and IKCa-mediated currents was explored in freshly dissociated ECs. NS309 evoked a potent vasodilation that was effectively inhibited by TRAM-34 but not by apamin. NS309-induced smooth muscle cell intracellular Ca(2+) concentration, membrane potential, and dilator responses were significantly diminished by diabetes; N-cyclohexyl-N-2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-4-pyrimidinamine (CyPPA)-evoked responses were not affected. Ca(2+)-activated ion currents in ECs were insensitive to paxilline, markedly inhibited by charybdotoxin (ChTX), and diminished by apamin. NS309-induced EC currents were generated mostly due to activation of ChTX-sensitive channels. Maternal diabetes resulted in a significant reduction in ChTX-sensitive currents with no effect on apamin-sensitive or CyPPA-induced currents. We concluded that IKCa channels play a prevalent role over SKCa channels in the generation of endothelial K(+) currents and vasodilation of uteroplacental arteries. Impaired function of IKCa channels importantly contributes to diabetes-induced uterine endothelial dysfunction. Therapeutic restoration of IKCa channel function may be a novel strategy for improvement of maternal uteroplacental blood flow in

  18. Endothelial plasmalemmal vesicles have a characteristic striped bipolar surface structure.

    Science.gov (United States)

    Peters, K R; Carley, W W; Palade, G E

    1985-12-01

    Capillary endothelial cells have a large population of small (65-80 nm diameter in transmission electron microscopy) vesicles of which a large fraction is associated with the plasmalemma of the luminal and abluminal side. We studied the fine structure and distribution of these plasmalemmal vesicles by high resolution scanning electron microscopy in cultured endothelial cells obtained from bovine adrenal cortical capillaries. Cell monolayers were covered with polylysine-coated silicon chips, split in high potassium buffer, fixed in aldehyde mixtures, and then treated with OsO4 and thiocarbohydrazide. After critical point drying, the specimens were coated with a thin (less than 2 nm) continuous film of chromium. On the cytoplasmic aspect of the dorsal plasmalemmal fragments seen in such specimens, plasmalemmal vesicles appear as uniform vesicular protrusions approximately 70-90 nm in diameter, preferentially concentrated in distinct large fields in which they occur primarily as single units. Individual plasmalemmal vesicles exhibit a striped surface fine structure which consists of ridges approximately 10 nm in diameter, separated by furrows and oriented as meridians, often ending at two poles on opposite sides of the vesicles in a plane parallel to the plasmalemma. This striped surface structure is clearly distinct from the cage structure of coated pits found, at low surface density, on the same specimens. The cytoplasmic aspect of the plasmalemma proper is covered by a fibrillar infrastructure which does not extend over plasmalemmal vesicles but on which the latter appear to be anchored by fine filaments.

  19. Presubiculum stimulation in vivo evokes distinct oscillations in superficial and deep entorhinal cortex layers in chronic epileptic rats

    NARCIS (Netherlands)

    Tolner, E.A.; Kloosterman, F.; van Vliet, E.A.; Witter, M.P.; Lopes da Silva, F.H.; Gorter, J.A.

    2005-01-01

    The characteristic cell loss in layer III of the medial entorhinal area (MEA-III) in human mesial temporal lobe epilepsy is reproduced in the rat kainate model of the disease. To understand how this cell loss affects the functional properties of the MEA, we investigated whether projections from the

  20. Central and peripheral chemoreceptors evoke distinct responses in simultaneously recorded neurons of the raphé-pontomedullary respiratory network

    OpenAIRE

    Nuding, Sarah C.; Segers, Lauren S.; Shannon, Roger; O'Connor, Russell; Morris, Kendall F.; Lindsey, Bruce G.

    2009-01-01

    The brainstem network for generating and modulating the respiratory motor pattern includes neurons of the medullary ventrolateral respiratory column (VRC), dorsolateral pons (PRG) and raphé nuclei. Midline raphé neurons are proposed to be elements of a distributed brainstem system of central chemoreceptors, as well as modulators of central chemoreceptors at other sites, including the retrotrapezoid nucleus. Stimulation of the raphé system or peripheral chemoreceptors can induce a long-term fa...

  1. Central and peripheral chemoreceptors evoke distinct responses in simultaneously recorded neurons of the raphé-pontomedullary respiratory network.

    Science.gov (United States)

    Nuding, Sarah C; Segers, Lauren S; Shannon, Roger; O'Connor, Russell; Morris, Kendall F; Lindsey, Bruce G

    2009-09-12

    The brainstem network for generating and modulating the respiratory motor pattern includes neurons of the medullary ventrolateral respiratory column (VRC), dorsolateral pons (PRG) and raphé nuclei. Midline raphé neurons are proposed to be elements of a distributed brainstem system of central chemoreceptors, as well as modulators of central chemoreceptors at other sites, including the retrotrapezoid nucleus. Stimulation of the raphé system or peripheral chemoreceptors can induce a long-term facilitation of phrenic nerve activity; central chemoreceptor stimulation does not. The network mechanisms through which each class of chemoreceptor differentially influences breathing are poorly understood. Microelectrode arrays were used to monitor sets of spike trains from 114 PRG, 198 VRC and 166 midline neurons in six decerebrate vagotomized cats; 356 were recorded during sequential stimulation of both receptor classes via brief CO(2)-saturated saline injections in vertebral (central) and carotid arteries (peripheral). Seventy neurons responded to both stimuli. More neurons were responsive only to peripheral challenges than those responsive only to central chemoreceptor stimulation (PRG, 20 : 4; VRC, 41 : 10; midline, 25 : 13). Of 16 474 pairs of neurons evaluated for short-time scale correlations, similar percentages of reference neurons in each brain region had correlation features indicative of a specific interaction with at least one target neuron: PRG (59.6%), VRC (51.0%) and raphé nuclei (45.8%). The results suggest a brainstem network architecture with connectivity that shapes the respiratory motor pattern via overlapping circuits that modulate central and peripheral chemoreceptor-mediated influences on breathing.

  2. Clinical evaluation of cochlear hearing status in dogs using evoked otoacoustic emissions.

    Science.gov (United States)

    Gonçalves, R; McBrearty, A; Pratola, L; Calvo, G; Anderson, T J; Penderis, J

    2012-06-01

    Evoked otoacoustic emission testing is the preferred test in human patients for sensorineural deafness screening in neonates and cochlear outer hair cell function monitoring in adults. This study evaluated evoked otoacoustic emission testing for cochlear function assessment in dogs within a clinical setting. Two populations of anaesthetised dogs were included. In group 1 the evoked otoacoustic emission response was compared to the brainstem auditory evoked response in 10 dogs having hearing assessment. Group 2 comprised 43 presumed normal dogs, in which the suitability of two types of evoked otoacoustic emissions, transient-evoked and distortion product otoacoustic emissions, were evaluated (brainstem auditory evoked response was not performed in this group). Valid transient-evoked otoacoustic emission and distortion-product otoacoustic emission responses were successfully recorded within the clinical setting and correctly identified deaf and hearing ears. Within presumed healthy dogs, normal otoacoustic emission response was demonstrated in more than 80% of dogs using a single, short distortion-product otoacoustic emission run and in 78% of dogs with valid transient-evoked otoacoustic emission responses using a series of three repeated transient-evoked otoacoustic emission short runs. Transient-evoked otoacoustic emission and distortion-product otoacoustic emission testing provided a rapid, non-invasive frequency-specific assessment of cochlear function. Transient-evoked otoacoustic emission and distortion product otoacoustic emission testing is suitable as a screening procedure to detect loss of cochlear function in dogs, although further investigation is needed. © 2012 British Small Animal Veterinary Association.

  3. An inventory and update of jealousy-evoking partner behaviours in modern society.

    NARCIS (Netherlands)

    Dijkstra, Pieternel; Barelds, Dick P. H.; Groothof, Hinke A. K.

    2010-01-01

    The goal of the present study was to identify the most important jealousy-evoking partner behaviours and to examine the extent to which these behaviours evoke jealousy. Based on the literature, a questionnaire was constructed containing 42 jealousy-evoking partner behaviours, including a partner's

  4. Effects of shear on endothelial cell calcium in the presence and absence of ATP.

    Science.gov (United States)

    James, N L; Harrison, D G; Nerem, R M

    1995-07-01

    The purpose of this study was to characterize the effect of various shear conditions on endothelial cell intracellular calcium ([Ca2+]i). Bovine aortic endothelial cells (BAEC) were loaded with Fluo-3 and exposed to flow in a parallel plate flow chamber designed for confocal microscopy. The flow medium was medium 199 (M-199), which was prepared with and without adenosine triphosphate (ATP). In the presence of ATP, initiation of flow at a shear stress of 2.5 dyn/cm2 evoked a strong, sustained elevation of [Ca2+]i that gradually returned to baseline levels over 10 to 15 min. By contrast, in the absence of ATP, initiation of flow at 2.5 dyn/cm2 produced only transient increases in [Ca2+]i in a small proportion of the cells. As shear rate was increased from 2.5 to 15 dyn/cm2 in this medium, both the relative fluorescence of the monolayer and the proportion of cells across the monolayer that displayed calcium transients increased in a dose-dependent fashion. In conclusion, the response of an endothelial cell monolayer to increasing levels of shear is not only to increase [Ca2+]i within individual cells, but to increase the duration of response and the number of cells responding at the onset of shear. This recruitment of larger numbers of cells at higher levels of shear may represent a novel signaling mechanism within the endothelium.

  5. Circulating Endothelial Cells and Endothelial Progenitor Cells in Pediatric Sepsis.

    Science.gov (United States)

    Zahran, Asmaa Mohamad; Elsayh, Khalid Ibrahim; Mohamad, Ismail Lotfy; Hassan, Gamal Mohamad; Abdou, Madleen Adel A

    2016-03-01

    The aim of the study was to measure the number of circulating endothelial cells (CECs) and circulating endothelial progenitor cells (CEPs) in pediatric patients with sepsis and correlating it with the severity of the disease and its outcome. The study included 19 children with sepsis, 26 with complicated sepsis, and 30 healthy controls. The patients were investigated within 48 hours of pediatric intensive care unit admission together with flow cytometric detection of CECs and CEPs. The levels of both CECs and CEPs were significantly higher in patient with sepsis and complicated sepsis than the controls. The levels of CECs were higher in patients with complicated sepsis, whereas the levels of CEPs were lower in patients with complicated sepsis. Comparing the survival and nonsurvival septic patients, the levels of CEPs were significantly higher in the survival than in nonsurvival patients, whereas the levels of CECs were significantly lower in the survival than in nonsurvival patients. Serum albumin was higher in survival than in nonsurvival patients. Estimation of CECs and CEPs and their correlation with other parameters such as serum albumen could add important information regarding prognosis in septic pediatric patients.

  6. Functional characterization of S100A8 and S100A9 in altering monolayer permeability of human umbilical endothelial cells.

    Directory of Open Access Journals (Sweden)

    Liqun Wang

    Full Text Available S100A8, S100A9 and S100A8/A9 complexes have been known as important endogenous damage-associated molecular pattern (DAMP proteins. But the pathophysiological roles of S100A8, S100A9 and S100A8/A9 in cardiovascular diseases are incompletely explained. In this present study, the effects of homo S100A8, S100A9 and their hetero-complex S100A8/A9 on endothelial barrier function were tested respectively in cultured human umbilical venous endothelial cells (HUVECs. The involvement of TLR4 and RAGE were observed by using inhibitor of TLR4 and blocking antibody of RAGE. The clarification of different MAPK subtypes in S100A8/A9-induced endothelial response was implemented by using specific inhibitors. The calcium-dependency was detected in the absence of Ca2+ or in the presence of gradient-dose Ca2+. The results showed that S100A8, S100A9 and S100A8/A9 could induce F-actin and ZO-1 disorganization in HUVECs and evoked the increases of HUVEC monolayer permeability in a dose- and time-dependent manner. The effects of S100A8, S100A9 and S100A8/A9 on endothelial barrier function depended on the activation of p38 and ERK1/2 signal pathways through receptors TLR4 and RAGE. Most importantly, we revealed the preference of S100A8 on TLR4 and S100A9 on RAGE in HUVECs. The results also showed the calcium dependency in S100A8- and S100A9-evoked endothelial response, indicating that calcium dependency on formation of S100A8 or A9 dimmers might be the prerequisite for this endothelial functional alteration.

  7. [Motor evoked potentials of the perineal floor. Preliminary results].

    Science.gov (United States)

    Opsomer, R J; Van Cangh, P J; Humblet, Y; Abi Aad, A; Rossini, P M

    1989-01-01

    Neuromotor pathways from the brain to the pelvic floor have been poorly documented. The recent development of Motor Evoked Potentials may well fill this gap in our basic knowledge. Our technique consists of transcutaneous stimulation of the motor cortex and sacral roots with a magnetic device while recording the evoked response from the bulbocavernosus muscle and anal sphincter. Cortical stimulation is performed first at rest and then during voluntary contraction of the examined muscles ("facilitation" procedure). Sacral root stimulation is performed at rest. Stimulation at 2 different levels allows measurement of the total transit time (brain to muscle transit time) and the peripheral transit time (sacral roots to muscle). By subtracting the latter from the former, the central transit time (brain to sacral roots) is obtained. The technique is painless, and to our knowledge no side effects have been reported. The authors present the preliminary results of this new technique.

  8. Evoked potentials and head injury. 2. Clinical applications.

    Science.gov (United States)

    Rappaport, M; Hopkins, H K; Hall, K; Belleza, T

    1981-10-01

    The method of rating abnormality of evoked brain potential patterns and assessing the extent and severity of cortical and subcortical brain dysfunction in head injury patients described in Part I is applied in a clinical context. Evoked potential abnormality (EPA) scores are found to be significantly correlated both with admission and outcome disability approximately one year after head injury. Correlations increase with the increase in the number of sensory modalities tested. Correlations between EPA scores and clinical disability (measured by the Disability Rating Scale) decrease with time after injury. Significant correlations, however, persist for about 60 days after onset of injury. It was found that EP pattern abnormalities can reflect specific sensory (and at times motor) deficits in noncommunicative patients and thereby contribute significantly to early treatment and rehabilitation planning.

  9. Binocular interactions in the guinea pig's visual-evoked potentials.

    Science.gov (United States)

    Ates, Kahraman; Demirtas, Serdar; Goksoy, Cuneyt

    2006-12-13

    In this study, binocular interaction in guinea pigs is evaluated using bioelectrical activities. A difference potential, as evidence of an interaction, is calculated by subtracting the sum of visual-evoked potentials recorded by left and right monocular visual stimulations from the potential recorded by binocular stimulation. A negative monophasic wave with an average amplitude of 15.1 microV and an average latency of 106 ms is observed in the difference potential. This finding implies that the P100 is the main guinea pig visual-evoked potential wave that is affected by binocular interaction. Binocular interaction is also observed in the waves N75 and N140, although with a smaller amplitude. No interaction is observed in the segments of P55 and P200 waves.

  10. Multimodality evoked potentials in occupational exposure to metallic mercury vapour.

    Science.gov (United States)

    Langauer-Lewowicka, H; Kazibutowska, Z

    1989-01-01

    Central nervous system dysfunction among workers exposed to metallic mercury was studied by measuring somatosensory evoked potentials (SSEPs) and visual evoked potentials (VEPs). The examinations were conducted in 28 workers suspected of chronic mercury intoxication. They were exposed to Hg for a period ranging from 4-34 years (mean 22.1) in an acetic aldehyde and chlorine manufacturing plant. The increase of amplitude of N20 SSEP (13 cases) and elongation of its latency were frequent abnormalities in the examined group. The latency of N20 was significantly longer in the exposed group in comparison with the control one, the amplitude of N20 was also significantly higher. Significantly prolonged latency of P100 VEP was found in the group exposed to Hg. These findings suggest the possibility of an adverse effect due to Hg on the central part of the somatosensory and visual pathway.

  11. Automatic classification of visual evoked potentials based on wavelet decomposition

    Science.gov (United States)

    Stasiakiewicz, Paweł; Dobrowolski, Andrzej P.; Tomczykiewicz, Kazimierz

    2017-04-01

    Diagnosis of part of the visual system, that is responsible for conducting compound action potential, is generally based on visual evoked potentials generated as a result of stimulation of the eye by external light source. The condition of patient's visual path is assessed by set of parameters that describe the time domain characteristic extremes called waves. The decision process is compound therefore diagnosis significantly depends on experience of a doctor. The authors developed a procedure - based on wavelet decomposition and linear discriminant analysis - that ensures automatic classification of visual evoked potentials. The algorithm enables to assign individual case to normal or pathological class. The proposed classifier has a 96,4% sensitivity at 10,4% probability of false alarm in a group of 220 cases and area under curve ROC equals to 0,96 which, from the medical point of view, is a very good result.

  12. Evoked response audiometry used in testing auditory organs of miners

    Energy Technology Data Exchange (ETDEWEB)

    Malinowski, T.; Klepacki, J.; Wagstyl, R.

    1980-01-01

    The evoked response audiometry method of testing hearing loss is presented and the results of comparative studies using subjective tonal audiometry and evoked response audiometry in tests of 56 healthy men with good hearing are discussed. The men were divided into three groups according to age and place of work: work place without increased noise; work place with noise and vibrations (at drilling machines); work place with noise and shocks (work at excavators in surface coal mines). The ERA-MKII audiometer produced by the Medelec-Amplaid firm was used. Audiometric threshhold curves for the three groups of tested men are given. At frequencies of 500, 1000 and 4000 Hz mean objective auditory threshhold was shifted by 4-9.5 dB in comparison to the subjective auditory threshold. (21 refs.) (In Polish)

  13. Abdominal acupuncture reduces laser-evoked potentials in healthy subjects

    DEFF Research Database (Denmark)

    Pazzaglia, C.; Liguori, S.; Minciotti, I.

    2015-01-01

    Objective: Acupuncture is known to reduce clinical pain, although the exact mechanism is unknown. The aim of the current study was to investigate the effect of acupuncture on laser-evoked potential amplitudes and laser pain perception. Methods: In order to evaluate whether abdominal acupuncture...... is able to modify pain perception, 10 healthy subjects underwent a protocol in which laser-evoked potentials (LEPs) and laser pain perception were collected before the test (baseline), during abdominal acupuncture, and 15. min after needle removal. The same subjects also underwent a similar protocol...... in which, however, sham acupuncture without any needle penetration was used. Results: During real acupuncture, both N1 and N2/P2 amplitudes were reduced, as compared to baseline (p . < 0.01). The reduction lasted up to 15. min after needle removal. Furthermore, laser pain perception was reduced during...

  14. Counselor Identity: Conformity or Distinction?

    Science.gov (United States)

    McLaughlin, Jerry E.; Boettcher, Kathryn

    2009-01-01

    The authors explore 3 debates in other disciplines similar to counseling's identity debate in order to learn about common themes and outcomes. Conformity, distinction, and cohesion emerged as common themes. They conclude that counselors should retain their distinctive, humanistic approach rather than conforming to the dominant, medical approach.

  15. The Dynamic Functional Capacity Theory: Music Evoked Emotions

    OpenAIRE

    Klineburger, Philip C

    2014-01-01

    The music-evoked emotion literature implicates many brain regions involved in emotional processing but is currently lacking a model that specifically explains how they temporally and dynamically interact to produce intensely pleasurable emotions. A conceptual model, The Dynamic Functional Capacity Theory (DFCT), is proposed that provides a foundation for the further understanding of how brain regions interact to produce intense intensely pleasurable emotions. The DFCT claims th...

  16. Multimodality evoked potentials in HTLV-I associated myelopathy.

    OpenAIRE

    Kakigi, R; Shibasaki, H; Kuroda, Y; Endo, C; Oda, K; Ikeda, A; Hashimoto, K

    1988-01-01

    Multimodality evoked potentials (EPs) consisting of somatosensory EPs (SEPs), visual EPs (VEPs) and brainstem auditory EPs (BAEPs) were studied in 16 cases with HTLV-I associated myelopathy (HAM). Median nerve SEPs were normal in all cases. In posterior tibial nerve SEPs, the potential recorded at the 12th thoracic spinal process was normal in every case but cortical components were significantly prolonged in 10 cases, although five of these showed no sensory impairment. BAEPs were normal in ...

  17. Establishing an evoked-potential vision-tracking system

    Science.gov (United States)

    Skidmore, Trent A.

    1991-01-01

    This paper presents experimental evidence to support the feasibility of an evoked-potential vision-tracking system. The topics discussed are stimulator construction, verification of the photic driving response in the electroencephalogram, a method for performing frequency separation, and a transient-analysis example. The final issue considered is that of object multiplicity (concurrent visual stimuli with different flashing rates). The paper concludes by discussing several applications currently under investigation.

  18. Differences in cortical coding of heat evoked pain beyond the perceived intensity: an fMRI and EEG study.

    Science.gov (United States)

    Haefeli, Jenny; Freund, Patrick; Kramer, John L K; Blum, Julia; Luechinger, Roger; Curt, Armin

    2014-04-01

    Imaging studies have identified a wide network of brain areas activated by nociceptive stimuli and revealed differences in somatotopic representation of highly distinct stimulation sites (foot vs. hand) in the primary (S1) and secondary (S2) somatosensory cortices. Somatotopic organization between adjacent dermatomes and differences in cortical coding of similarly perceived nociceptive stimulation are less well studied. Here, cortical processing following contact heat nociceptive stimulation of cervical (C4, C6, and C8) and trunk (T10) dermatomes were recorded in 20 healthy subjects using functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). Stimulation of T10 compared with the C6 and C8 revealed significant higher response intensity in the left S1 (contralateral) and the right S2 (ipsilateral) even when the perceived pain was equal between stimulation sites. Accordingly, contact heat evoked potentials following stimulation of T10 showed significantly higher N2P2 amplitudes compared to C6 and C8. Adjacent dermatomes did not reveal a distinct somatotopical representation. Within the assessed cervical and trunk dermatomes, nociceptive cortical processing to heat differs significantly in magnitude even when controlling for pain perception. This study provides evidence that controlling for pain perception is not sufficient to compare directly the magnitude of cortical processing [blood oxygen level dependence (BOLD) response and amplitude of evoked potentials] between body sites. Copyright © 2013 Wiley Periodicals, Inc.

  19. Perceptual learning of acoustic noise generates memory-evoked potentials.

    Science.gov (United States)

    Andrillon, Thomas; Kouider, Sid; Agus, Trevor; Pressnitzer, Daniel

    2015-11-02

    Experience continuously imprints on the brain at all stages of life. The traces it leaves behind can produce perceptual learning [1], which drives adaptive behavior to previously encountered stimuli. Recently, it has been shown that even random noise, a type of sound devoid of acoustic structure, can trigger fast and robust perceptual learning after repeated exposure [2]. Here, by combining psychophysics, electroencephalography (EEG), and modeling, we show that the perceptual learning of noise is associated with evoked potentials, without any salient physical discontinuity or obvious acoustic landmark in the sound. Rather, the potentials appeared whenever a memory trace was observed behaviorally. Such memory-evoked potentials were characterized by early latencies and auditory topographies, consistent with a sensory origin. Furthermore, they were generated even on conditions of diverted attention. The EEG waveforms could be modeled as standard evoked responses to auditory events (N1-P2) [3], triggered by idiosyncratic perceptual features acquired through learning. Thus, we argue that the learning of noise is accompanied by the rapid formation of sharp neural selectivity to arbitrary and complex acoustic patterns, within sensory regions. Such a mechanism bridges the gap between the short-term and longer-term plasticity observed in the learning of noise [2, 4-6]. It could also be key to the processing of natural sounds within auditory cortices [7], suggesting that the neural code for sound source identification will be shaped by experience as well as by acoustics. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Brainstem auditory evoked potentials in children with lead exposure

    Directory of Open Access Journals (Sweden)

    Katia de Freitas Alvarenga

    2015-02-01

    Full Text Available Introduction: Earlier studies have demonstrated an auditory effect of lead exposure in children, but information on the effects of low chronic exposures needs to be further elucidated. Objective: To investigate the effect of low chronic exposures of the auditory system in children with a history of low blood lead levels, using an auditory electrophysiological test. Methods: Contemporary cross-sectional cohort. Study participants underwent tympanometry, pure tone and speech audiometry, transient evoked otoacoustic emissions, and brainstem auditory evoked potentials, with blood lead monitoring over a period of 35.5 months. The study included 130 children, with ages ranging from 18 months to 14 years, 5 months (mean age 6 years, 8 months ± 3 years, 2 months. Results: The mean time-integrated cumulative blood lead index was 12 µg/dL (SD ± 5.7, range:2.433. All participants had hearing thresholds equal to or below 20 dBHL and normal amplitudes of transient evoked otoacoustic emissions. No association was found between the absolute latencies of waves I, III, and V, the interpeak latencies I-III, III-V, and I-V, and the cumulative lead values. Conclusion: No evidence of toxic effects from chronic low lead exposures was observed on the auditory function of children living in a lead contaminated area.

  1. Brainstem auditory evoked potentials in children with lead exposure.

    Science.gov (United States)

    Alvarenga, Katia de Freitas; Morata, Thais Catalani; Lopes, Andrea Cintra; Feniman, Mariza Ribeiro; Corteletti, Lilian Cassia Bornia Jacob

    2015-01-01

    Earlier studies have demonstrated an auditory effect of lead exposure in children, but information on the effects of low chronic exposures needs to be further elucidated. To investigate the effect of low chronic exposures of the auditory system in children with a history of low blood lead levels, using an auditory electrophysiological test. Contemporary cross-sectional cohort. Study participants underwent tympanometry, pure tone and speech audiometry, transient evoked otoacoustic emissions, and brainstem auditory evoked potentials, with blood lead monitoring over a period of 35.5 months. The study included 130 children, with ages ranging from 18 months to 14 years, 5 months (mean age 6 years, 8 months ± 3 years, 2 months). The mean time-integrated cumulative blood lead index was 12 μg/dL (SD ± 5.7, range: 2.433). All participants had hearing thresholds equal to or below 20 dBHL and normal amplitudes of transient evoked otoacoustic emissions. No association was found between the absolute latencies of waves I, III, and V, the interpeak latencies I-III, III-V, and I-V, and the cumulative lead values. No evidence of toxic effects from chronic low lead exposures was observed on the auditory function of children living in a lead contaminated area. Copyright © 2014 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  2. Index finger somatosensory evoked potentials in blind Braille readers.

    Science.gov (United States)

    Giriyappa, Dayananda; Subrahmanyam, Roopakala Mysore; Rangashetty, Srinivasa; Sharma, Rajeev

    2009-01-01

    Traditionally, vision has been considered the dominant modality in our multi-sensory perception of the surrounding world. Sensory input via non-visual tracts becomes of greater behavioural relevance in totally blind individuals to enable effective interaction with the world around them. These include audition and tactile perceptions, leading to an augmentation in these perceptions when compared with normal sighted individuals. The objective of the present work was to study the index finger somatosensory evoked potentials (SEPs) in totally blind and normal sighted individuals. SEPs were recorded in 15 Braille reading totally blind females and compared with 15 age-matched normal sighted females. Latency and amplitudes of somatosensory evoked potential waveforms (N9, N13, and N20) were measured. Amplitude of N20 SEP (a cortical somatosensory evoked potential) was significantly larger in the totally blind than in normal sighted individuals (p Braille reading right index finger. Totally blind Braille readers have larger N20 amplitude, suggestive of greater somatosensory cortical representation of the Braille reading index finger.

  3. Auditory evoked potentials in children and adolescents with Down syndrome.

    Science.gov (United States)

    Gregory, Letícia; Rosa, Rafael F M; Zen, Paulo R G; Sleifer, Pricila

    2018-01-01

    Down syndrome, or trisomy 21, is the most common genetic alteration in humans. The syndrome presents with several features, including hearing loss and changes in the central nervous system, which may affect language development in children and lead to school difficulties. The present study aimed to investigate group differences in the central auditory system by long-latency auditory evoked potentials and cognitive potential. An assessment of 23 children and adolescents with Down syndrome was performed, and a control group composed of 43 children and adolescents without genetic and/or neurological changes was used for comparison. All children underwent evaluation with pure tone and vocal audiometry, acoustic immitance measures, long-latency auditory evoked potentials, and cognitive potential. Longer latencies of the waves were found in the Down syndrome group than the control group, without significant differences in amplitude, suggesting that individuals with Down syndrome have difficulty in discrimination and auditory memory. It is, therefore, important to stimulate and monitor these children in order to enable adequate development and improve their life quality. We also emphasize the importance of the application of auditory evoked potentials in clinical practice, in order to contribute to the early diagnosis of hearing alterations and the development of more research in this area. © 2017 Wiley Periodicals, Inc.

  4. Endothelial progenitor cell dysfunction in diabetes mellitus

    NARCIS (Netherlands)

    Loomans, Cindy Johanna Maria

    2007-01-01

    Postnatally, Endothelial Progenitor Cells are needed to maintain the integrity of the endothelium (re-endothelialization) and to augment wound healing or vascularize hypoxic areas (neovascularization). Complex networks of different signals and regulators have been identified to be involved in these

  5. Endothelial dysfunction after non-cardiac surgery

    DEFF Research Database (Denmark)

    Søndergaard, E S; Fonnes, S; Gögenur, I

    2015-01-01

    was to systematically review the literature to evaluate the association between non-cardiac surgery and non-invasive markers of endothelial function. METHODS: A systematic search was conducted in MEDLINE, EMBASE and Cochrane Library Database according to the PRISMA guidelines. Endothelial dysfunction was described only...

  6. PPAR Gamma and Angiogenesis: Endothelial Cells Perspective

    Directory of Open Access Journals (Sweden)

    Jerzy Kotlinowski

    2016-01-01

    Full Text Available We summarize the current knowledge concerning PPARγ function in angiogenesis. We discuss the mechanisms of action for PPARγ and its role in vasculature development and homeostasis, focusing on endothelial cells, endothelial progenitor cells, and bone marrow-derived proangiogenic cells.

  7. Binaural interaction in auditory evoked potentials: Brainstem, middle- and long-latency components

    OpenAIRE

    McPherson, DL; Starr, A

    1993-01-01

    Binaural interaction occurs in the auditory evoked potentials when the sum of the monaural auditory evoked potentials are not equivalent to the binaural evoked auditory potentials. Binaural interaction of the early- (0-10 ms), middle- (10-50 ms) and long-latency (50-200 ms) auditory evoked potentials was studied in 17 normal young adults. For the early components, binaural interaction was maximal at 7.35 ms accounting for a reduction of 21% of the amplitude of the binaural evoked potentials. ...

  8. Molecular expression in transfected corneal endothelial cells

    Science.gov (United States)

    Wang, Fan; Miao, Zhuang; Lu, Chengwei; Hao, Jilong

    2017-10-01

    To investigate the capability of human corneal endothelial cells serving as immunological cells. Expression of HLA-DP, -DQ, -DR, CD40, CD80, and CD86 was determined by immunohistochemical methods. Meanwhile, purified peripheral blood mononuclear cells were cocultured with human corneal endothelial cells which were pre-treated with and without -IFN respectively, activation of lymphocytes was determined by FACS analysis. In coculture system, T lymphocyte was activated by corneal endothelial cells, HLA-DP, -DQ, -DR and CD40 expression were increased by - IFN induction. Costimulatory molecular CD80 was shown on the endothelial cells. Human corneal endothelial cells were assumed to be involved in the corneal transplantation rejection process as potential antigen presenting cells.

  9. Glomerular input patterns in the mouse olfactory bulb evoked by retronasal odor stimuli.

    Science.gov (United States)

    Furudono, Yuichi; Cruz, Ginny; Lowe, Graeme

    2013-04-08

    Odorant stimuli can access the olfactory epithelium either orthonasally, by inhalation through the external nares, or retronasally by reverse airflow from the oral cavity. There is evidence that odors perceived through these two routes can differ in quality and intensity. We were curious whether such differences might potentially have a neural basis in the peripheral mechanisms of odor coding. To explore this possibility, we compared olfactory receptor input to glomeruli in the dorsal olfactory bulb evoked by orthonasal and retronasal stimulation. Maps of glomerular response were acquired by optical imaging of transgenic mice expressing synaptopHluorin (spH), a fluorescent reporter of presynaptic activity, in olfactory nerve terminals. We found that retronasally delivered odorants were able to activate inputs to multiple glomeruli in the dorsal olfactory bulb. The retronasal responses were smaller than orthonasal responses to odorants delivered at comparable concentrations and flow rates, and they displayed higher thresholds and right-shifted dose-response curves. Glomerular maps of orthonasal and retronasal responses were usually well overlapped, with fewer total numbers of glomeruli in retronasal maps. However, maps at threshold could be quite distinct with little overlap. Retronasal responses were also more narrowly tuned to homologous series of aliphatic odorants of varying carbon chain length, with longer chain, more hydrophobic compounds evoking little or no response at comparable vapor levels. Several features of retronasal olfaction are possibly referable to the observed properties of glomerular odorant responses. The finding that retronasal responses are weaker and sparser than orthonasal responses is consistent with psychophysical studies showing lower sensitivity for retronasal olfaction in threshold and suprathreshold tests. The similarity and overlap of orthonasal and retronasal odor maps at suprathreshold concentrations agrees with generally similar

  10. SNAP23 Regulates Endothelial Exocytosis of von Willebrand Factor.

    Science.gov (United States)

    Zhu, Qiuyu Martin; Zhu, Qiuyu; Yamakuchi, Munekazu; Lowenstein, Charles J

    2015-01-01

    Endothelial exocytosis regulates vascular thrombosis and inflammation. The trafficking and release of endothelial vesicles is mediated by SNARE (Soluble NSF Attachment protein REceptors) molecules, but the exact identity of endothelial SNAREs has been unclear. Three SNARE molecules form a ternary complex, including isoforms of the syntaxin (STX), vesicle-associated membrane protein (VAMP), and synaptosomal-associated protein (SNAP) families. We now identify SNAP23 as the predominant endothelial SNAP isoform that mediates endothelial exocytosis of von Willebrand Factor (VWF). SNAP23 was localized to the plasma membrane. Knockdown of SNAP23 decreased endothelial exocytosis, suggesting it is important for endothelial exocytosis. SNAP23 interacted with the endothelial exocytic machinery, and formed complexes with other known endothelial SNARE molecules. Taken together, these data suggest that SNAP23 is a key component of the endothelial SNARE machinery that mediates endothelial exocytosis.

  11. Microvascular Coronary Artery Spasm Presents Distinctive Clinical Features With Endothelial Dysfunction as Nonobstructive Coronary Artery Disease

    OpenAIRE

    Ohba, Keisuke; Sugiyama, Seigo; Sumida, Hitoshi; Nozaki, Toshimitsu; Matsubara, Junichi; Matsuzawa, Yasushi; Konishi, Masaaki; Akiyama, Eiichi; Kurokawa, Hirofumi; Maeda, Hirofumi; Sugamura, Koichi; Nagayoshi, Yasuhiro; Morihisa, Kenji; Sakamoto, Kenji; Tsujita, Kenichi

    2012-01-01

    Background Angina without significant stenosis, or nonobstructive coronary artery disease, attracts clinical attention. Microvascular coronary artery spasm (microvascular CAS) can cause nonobstructive coronary artery disease. We investigated the clinical features of microvascular CAS and the therapeutic efficacy of calcium channel blockers. Methods and Results Three hundred seventy consecutive, stable patients with suspected angina presenting nonobstructive coronary arteries (

  12. Validation of the State-Trait Distinction in Anxiety Research.

    Science.gov (United States)

    Gaudry, E; Vagg, P; Spielberger, C D

    1975-07-01

    High school and university students were given Sarason's Test Anxiety Scale for Children, an intelligence test, and the A-State and A-Trait Scales of Spielberger's State-Trait Anxiety Inventory (STAI). The STAI A-Stake Scale was administered under one non-stress and two stress conditions to both groups of subjects. A factor analysis of the data for the high school students identified six factors: trait anxiety; t h e e separate state anxiety factors, corresponding to each of the three administrations of the A-State Scale; a reversed-item factor; and an ability factor. A similar factor pattern emerged for the university students. The results were interpreted as providing evidence of the importance of situational stress in evoking anxiety states, and strong support for the slate-trait distinction in anxiety research.

  13. [Transplantation of corneal endothelial cells].

    Science.gov (United States)

    Amano, Shiro

    2002-12-01

    Though conventional corneal transplantation has achieved great success, it still has several drawbacks including limited availability of donor corneas, recurrent allograft rejection, and subsequent graft failure in certain cases. Reconstructing clinically usable corneas by applying the technology of regenerative medicine can offer a solution to these problems, as well as making corneal transplantation a non-emergency surgery and enabling the usage of banked corneal cells. In the present study, we focused on corneal endothelium that is critical for corneal transparency and investigated the reconstruction of cornea utilizing cultured human corneal endothelial cells (HCECs). We succeeded in steadily culturing HCECs by using culture dishes pre-coated with extracellular matrix produced by calf corneal endothelial cells and culture media that contained basic fibroblast growth factor and fetal bovine serum. We performed the following analysis utilizing these cultured HCECs. The older the donor was, the more frequently large senescent cells appeared in the passaged HCECs. The telomeres of HCECs were measured as terminal restriction fragments (TRF) by Southern blotting. HCECs, in vivo from donors in their seventies had a long TRFs of over 12 kilobases. Passaging shortened the TRFs but there was no difference in TRFs among donors of various ages. These results indicated that shortening of telomere length is not related to senescence of HCECs. We investigated the role of advanced glycation end products (AGEs) in the senescence of in vivo HCECs. The results indicated that AGE-protein in the aqueous humor is endocytosed into HCECs via AGE receptors expressed on the surface of HCECs and damages HCECs by producing reactive oxygen species and inducing apoptosis, suggesting that AGEs, at least partly, cause the senescence of HECEs. HCECs were cultured using adult human serum instead of bovine serum to get rid of bovine material that can be infected with prions. Primary and passage

  14. Endothelial Nitric Oxide Mediates Caffeine Antagonism of Alcohol-Induced Cerebral Artery Constriction

    Science.gov (United States)

    Chang, Jennifer; Fedinec, Alexander L.; Kuntamallappanavar, Guruprasad; Leffler, Charles W.; Bukiya, Anna N.

    2016-01-01

    Despite preventive education, the combined consumption of alcohol and caffeine (particularly from “energy drinks”) continues to rise. Physiologic perturbations by separate intake of ethanol and caffeine have been widely documented. However, the biologic actions of the alcohol-caffeine combination and their underlying subcellular mechanisms have been scarcely studied. Using intravital microscopy on a closed-cranial window and isolated, pressurized vessels, we investigated the in vivo and in vitro action of ethanol-caffeine mixtures on cerebral arteries from rats and mice, widely recognized models to address cerebrovascular pathophysiology and pharmacology. Caffeine at concentrations found in human circulation after ingestion of one to two cups of coffee (10 µM) antagonized the endothelium-independent constriction of cerebral arteries evoked by ethanol concentrations found in blood during moderate-heavy alcohol intoxication (40–70 mM). Caffeine antagonism against alcohol was similar whether evaluated in vivo or in vitro, suggesting independence of systemic factors and drug metabolism, but required a functional endothelium. Moreover, caffeine protection against alcohol increased nitric oxide (NO•) levels over those found in the presence of ethanol alone, disappeared upon blocking NO• synthase, and could not be detected in pressurized cerebral arteries from endothelial nitric-oxide synthase knockout (eNOS−/−) mice. Finally, incubation of de-endothelialized cerebral arteries with the NO• donor sodium nitroprusside (10 µM) fully restored the protective effect of caffeine. This study demonstrates for the first time that caffeine antagonizes ethanol-induced cerebral artery constriction and identifies endothelial NO• as the critical caffeine effector on smooth muscle targets. Conceivably, situations that perturb endothelial function and/or NO• availability will critically alter caffeine antagonism of alcohol-induced cerebrovascular constriction without

  15. Endothelial Nitric Oxide Mediates Caffeine Antagonism of Alcohol-Induced Cerebral Artery Constriction.

    Science.gov (United States)

    Chang, Jennifer; Fedinec, Alexander L; Kuntamallappanavar, Guruprasad; Leffler, Charles W; Bukiya, Anna N; Dopico, Alex M

    2016-01-01

    Despite preventive education, the combined consumption of alcohol and caffeine (particularly from "energy drinks") continues to rise. Physiologic perturbations by separate intake of ethanol and caffeine have been widely documented. However, the biologic actions of the alcohol-caffeine combination and their underlying subcellular mechanisms have been scarcely studied. Using intravital microscopy on a closed-cranial window and isolated, pressurized vessels, we investigated the in vivo and in vitro action of ethanol-caffeine mixtures on cerebral arteries from rats and mice, widely recognized models to address cerebrovascular pathophysiology and pharmacology. Caffeine at concentrations found in human circulation after ingestion of one to two cups of coffee (10 µM) antagonized the endothelium-independent constriction of cerebral arteries evoked by ethanol concentrations found in blood during moderate-heavy alcohol intoxication (40-70 mM). Caffeine antagonism against alcohol was similar whether evaluated in vivo or in vitro, suggesting independence of systemic factors and drug metabolism, but required a functional endothelium. Moreover, caffeine protection against alcohol increased nitric oxide (NO•) levels over those found in the presence of ethanol alone, disappeared upon blocking NO• synthase, and could not be detected in pressurized cerebral arteries from endothelial nitric-oxide synthase knockout (eNOS(-/-)) mice. Finally, incubation of de-endothelialized cerebral arteries with the NO• donor sodium nitroprusside (10 µM) fully restored the protective effect of caffeine. This study demonstrates for the first time that caffeine antagonizes ethanol-induced cerebral artery constriction and identifies endothelial NO• as the critical caffeine effector on smooth muscle targets. Conceivably, situations that perturb endothelial function and/or NO• availability will critically alter caffeine antagonism of alcohol-induced cerebrovascular constriction without

  16. Resveratrol and Endothelial Nitric Oxide

    Directory of Open Access Journals (Sweden)

    Ning Xia

    2014-10-01

    Full Text Available Nitric oxide (NO derived from the endothelial NO synthase (eNOS has antihypertensive, antithrombotic, anti-atherosclerotic and antiobesogenic properties. Resveratrol is a polyphenol phytoalexin with multiple cardiovascular and metabolic effects. Part of the beneficial effects of resveratrol are mediated by eNOS. Resveratrol stimulates NO production from eNOS by a number of mechanisms, including upregulation of eNOS expression, stimulation of eNOS enzymatic activity and reversal of eNOS uncoupling. In addition, by reducing oxidative stress, resveratrol prevents oxidative NO inactivation by superoxide thereby enhancing NO bioavailability. Molecular pathways underlying these effects of resveratrol involve SIRT1, AMPK, Nrf2 and estrogen receptors.

  17. Dysfunctional Endothelial Progenitor Cells in Metabolic Syndrome

    Science.gov (United States)

    Devaraj, Sridevi; Jialal, Ishwarlal

    2012-01-01

    The metabolic syndrome (MetS) is highly prevalent and confers an increased risk of diabetes and cardiovascular disease. A key early event in atherosclerosis is endothelial dysfunction. Numerous groups have reported endothelial dysfunction in MetS. However, the measurement of endothelial function is far from optimum. There has been much interest recently in a subtype of progenitor cells, termed endothelial progenitor cells (EPCs), that can circulate, proliferate, and dfferentiate into mature endothelial cells. EPCs can be characterized by the assessment of surface markers, CD34 and vascular endothelial growth factor receptor-2, VEGFR-2 (KDR). The CD34+KDR+ phenotype has been demonstrated to be an independent predictor of cardiovascular outcomes. MetS patients without diabetes or cardiovascular diseases have decreased EPC number and functionality as evidenced by decreased numbers of colony forming units, decreased adhesion and migration, and decreased tubule formation. Strategies that have been shown to upregulate and enhance EPC number and functionality include statins, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and peroxisome-proliferator-activating-receptor gamma agonists. Mechanisms by which they affect EPC number and functionality need to be studied. Thus, EPC number and/or functionality could emerge as novel cellular biomarkers of endothelial dysfunction and cardiovascular disease risk in MetS. PMID:21941528

  18. Activation of endothelial toll-like receptor 3 impairs endothelial function.

    Science.gov (United States)

    Zimmer, Sebastian; Steinmetz, Martin; Asdonk, Tobias; Motz, Inga; Coch, Christoph; Hartmann, Evelyn; Barchet, Winfried; Wassmann, Sven; Hartmann, Gunther; Nickenig, Georg

    2011-05-27

    Endothelial dysfunction and atherosclerosis are chronic inflammatory diseases characterized by activation of the innate and acquired immune system. Specialized protein receptors of the innate immune system recognize products of microorganisms and endogenous ligands such as nucleic acids. Toll-like receptor 3 (TLR3), for example, detects long double-stranded RNA and is abundantly expressed in endothelial cells. Whether innate immunity contributes to atherogenic mechanisms in endothelial cells is poorly understood. We sought to determine the effects of TLR3 activation in endothelial cells. We first investigated whether stimulation of TLR3 influences endothelial biology in mice. Intravenous injection of polyinosine polycytidylic acid, a synthetic double-stranded RNA analog and TLR3 ligand, impaired endothelium-dependent vasodilation, increased vascular production of reactive oxygen species, and reduced reendothelialization after carotid artery injury in wild-type mice compared with controls but had no effect in TLR3(-/-) animals. TLR3 stimulation not only induced endothelial dysfunction but also enhanced the formation of atherosclerotic plaques in apolipoprotein E-deficient mice. In vitro incubation of endothelial cells with polyinosine polycytidylic acid induced production of the proinflammatory cytokines interleukin-8 and interferon-γ-induced protein 10, increased formation of reactive oxygen species, diminished proliferation, and increased apoptosis, which suggests that endothelial cells are able to directly detect and respond to TLR3 ligands. Neutralization of interleukin-8 and interferon-γ-induced protein 10 antagonizes the observed negative effects of polyinosine polycytidylic acid. We found elevated levels of circulating endothelial progenitor cells in polyinosine polycytidylic acid-treated mice, although they displayed increased endothelial dysfunction. Stimulation of TLR3 in cultured endothelial progenitor cells, however, led to increased formation of

  19. Fate of cerium dioxide nanoparticles in endothelial cells: exocytosis

    Science.gov (United States)

    Strobel, Claudia; Oehring, Hartmut; Herrmann, Rudolf; Förster, Martin; Reller, Armin; Hilger, Ingrid

    2015-05-01

    Although cytotoxicity and endocytosis of nanoparticles have been the subject of numerous studies, investigations regarding exocytosis as an important mechanism to reduce intracellular nanoparticle accumulation are rather rare and there is a distinct lack of knowledge. The current study investigated the behavior of human microvascular endothelial cells to exocytose cerium dioxide (CeO2) nanoparticles (18.8 nm) by utilization of specific inhibitors [brefeldin A; nocodazole; methyl-β-cyclodextrin (MβcD)] and different analytical methods (flow cytometry, transmission electron microscopy, inductively coupled plasma mass spectrometry). Overall, it was found that endothelial cells were able to release CeO2 nanoparticles via exocytosis after the migration of nanoparticle containing endosomes toward the plasma membrane. The exocytosis process occurred mainly by fusion of vesicular membranes with plasma membrane resulting in the discharge of vesicular content to extracellular environment. Nevertheless, it seems to be likely that nanoparticles present in the cytosol could leave the cells in a direct manner. MβcD treatment led to the strongest inhibition of the nanoparticle exocytosis indicating a significant role of the plasma membrane cholesterol content in the exocytosis process. Brefeldin A (inhibitor of Golgi-to-cell-surface-transport) caused a higher inhibitory effect on exocytosis than nocodazole (inhibitor of microtubules). Thus, the transfer from distal Golgi compartments to the cell surface influenced the exocytosis process of the CeO2 nanoparticles more than the microtubule-associated transport. In conclusion, endothelial cells, which came in contact with nanoparticles, e.g., after intravenously applied nano-based drugs, can regulate their intracellular nanoparticle amount, which is necessary to avoid adverse nanoparticle effects on cells.

  20. Two-photon optical microscopy imaging of endothelial keratoplasty grafts.

    Science.gov (United States)

    Lombardo, Marco; Parekh, Mohit; Serrao, Sebastiano; Ruzza, Alessandro; Ferrari, Stefano; Lombardo, Giuseppe

    2017-03-01

    To investigate the microstructure of endothelial keratoplasty grafts using two-photon optical microscopy. Six endothelial keratoplasty grafts obtained from human donor corneoscleral tissues and prepared by submerged hydrodissection technique were imaged by two-photon optical microscopy. In each graft, two liquid bubbles were created in order to investigate the presence of a conserved cleavage plane regardless of the volume of posterior stroma that remained attached to Descemet's membrane (DM); the first bubble (bubble A) was generated under DM and the second bubble (bubble B) injection was done in order to obtain a layer of deep stroma that kept the two bubbles separated. Six human donor corneoscleral tissues were used as controls. Second harmonic generation and two-photon emitted fluorescence signals were collected from each specimen. Dissection of stroma occurred along the posterior collagen lamellae at variable distance from DM, which ranged between 3 and 16 μm in bubble A and between 23 and 41 μm in bubble B. The residual stroma included, anteriorly, bands of collagen lamellae, and thin bundles of stromal collagen fibrils, posteriorly, which were tightly intertwining with the underlying DM. There was no anatomically distinct plane of separation between these pre-Descemetic stromal collagen bundles and the overlying collagen lamellae with this hydrodissection technique. Two-photon optical microscopy provided label-free high-resolution imaging of endothelial keratoplasty grafts, showing that the most posterior stroma changes organization at approximately 10 μm above the DM. The pre-Descemetic stromal collagen fibrils form an intertwined complex with DM, which cannot be separated using hydrodissection.

  1. Fate of cerium dioxide nanoparticles in endothelial cells: exocytosis

    Energy Technology Data Exchange (ETDEWEB)

    Strobel, Claudia, E-mail: Claudia.Strobel@med.uni-jena.de [Jena University Hospital – Friedrich Schiller University Jena, Department of Experimental Radiology, Institute of Diagnostic and Interventional Radiology (Germany); Oehring, Hartmut [Jena University Hospital – Friedrich Schiller University Jena, Institute of Anatomy II (Germany); Herrmann, Rudolf [University of Augsburg, Department of Physics (Germany); Förster, Martin [Jena University Hospital – Friedrich Schiller University Jena, Department of Internal Medicine I, Division of Pulmonary Medicine and Allergy/Immunology (Germany); Reller, Armin [University of Augsburg, Department of Physics (Germany); Hilger, Ingrid, E-mail: ingrid.hilger@med.uni-jena.de [Jena University Hospital – Friedrich Schiller University Jena, Department of Experimental Radiology, Institute of Diagnostic and Interventional Radiology (Germany)

    2015-05-15

    Although cytotoxicity and endocytosis of nanoparticles have been the subject of numerous studies, investigations regarding exocytosis as an important mechanism to reduce intracellular nanoparticle accumulation are rather rare and there is a distinct lack of knowledge. The current study investigated the behavior of human microvascular endothelial cells to exocytose cerium dioxide (CeO{sub 2}) nanoparticles (18.8 nm) by utilization of specific inhibitors [brefeldin A; nocodazole; methyl-β-cyclodextrin (MβcD)] and different analytical methods (flow cytometry, transmission electron microscopy, inductively coupled plasma mass spectrometry). Overall, it was found that endothelial cells were able to release CeO{sub 2} nanoparticles via exocytosis after the migration of nanoparticle containing endosomes toward the plasma membrane. The exocytosis process occurred mainly by fusion of vesicular membranes with plasma membrane resulting in the discharge of vesicular content to extracellular environment. Nevertheless, it seems to be likely that nanoparticles present in the cytosol could leave the cells in a direct manner. MβcD treatment led to the strongest inhibition of the nanoparticle exocytosis indicating a significant role of the plasma membrane cholesterol content in the exocytosis process. Brefeldin A (inhibitor of Golgi-to-cell-surface-transport) caused a higher inhibitory effect on exocytosis than nocodazole (inhibitor of microtubules). Thus, the transfer from distal Golgi compartments to the cell surface influenced the exocytosis process of the CeO{sub 2} nanoparticles more than the microtubule-associated transport. In conclusion, endothelial cells, which came in contact with nanoparticles, e.g., after intravenously applied nano-based drugs, can regulate their intracellular nanoparticle amount, which is necessary to avoid adverse nanoparticle effects on cells.

  2. The neonatal development of the light flash visual evoked potential.

    Science.gov (United States)

    Kraemer, M; Abrahamsson, M; Sjöström, A

    1999-01-01

    To follow visual development longitudinally in the normal neonate using the flash visual evoked potential (VEP) and to find indications for a relationship between potential development and visual development. Twenty healthy infants, born at term, were included in the study. Flash and patterned flash VEPs were used. The first VEP was recorded the day of birth or just postnatally, and succeeding recordings were performed the following weeks and months. The data revealed different types of VEP in the neonatal period suggesting great variability in visual function on the day of birth. In the early development a potential of long latency and duration preceded the development of a more compound potential of shorter latency. The two types of responses seemed to coalesce during early development; the first late response was attenuated and was eventually integrated in the more mature VEP. At approximately five weeks of age changes in the VEP were simultaneous with the development of responsive smiling and another visual behaviour of the infants. The results showed many similarities between the VEP development in infants and in immature animals. In developing animals geniculo-cortical and extra-geniculate visual afferent pathways evoke two types of VEPs similar to those recorded in the present study. The early responses were also similar to previous recordings from children with lesions in the geniculo-striatal pathway or primary cortex. Our interpretation of the results was that the human VEP also consists of responses evoked by afferents running both in geniculo-cortical and extra-geniculate pathways and that the two types of responses could be separated in the VEP in the neonatal period. These findings are important for our understanding of conditions with a delay in visual maturation, for example intracranial haemorrhages, hydrocephalus, pre/dys-maturity and 'idiopathic' delayed visual maturation.

  3. The division of attention and the human auditory evoked potential

    Science.gov (United States)

    Hink, R. F.; Van Voorhis, S. T.; Hillyard, S. A.; Smith, T. S.

    1977-01-01

    The sensitivity of the scalp-recorded, auditory evoked potential to selective attention was examined while subjects responded to stimuli presented to one ear (focused attention) and to both ears (divided attention). The amplitude of the N1 component was found to be largest to stimuli in the ear upon which attention was to be focused, smallest to stimuli in the ear to be ignored, and intermediate to stimuli in both ears when attention was divided. The results are interpreted as supporting a capacity model of attention.

  4. Brain stem auditory evoked responses in human infants and adults

    Science.gov (United States)

    Hecox, K.; Galambos, R.

    1974-01-01

    Brain stem evoked potentials were recorded by conventional scalp electrodes in infants (3 weeks to 3 years of age) and adults. The latency of one of the major response components (wave V) is shown to be a function both of click intensity and the age of the subject; this latency at a given signal strength shortens postnatally to reach the adult value (about 6 msec) by 12 to 18 months of age. The demonstrated reliability and limited variability of these brain stem electrophysiological responses provide the basis for an optimistic estimate of their usefulness as an objective method for assessing hearing in infants and adults.

  5. The Electrically Evoked Compound Action Potential: From Laboratory to Clinic.

    Science.gov (United States)

    He, Shuman; Teagle, Holly F B; Buchman, Craig A

    2017-01-01

    The electrically evoked compound action potential (eCAP) represents the synchronous firing of a population of electrically stimulated auditory nerve fibers. It can be directly recorded on a surgically exposed nerve trunk in animals or from an intra-cochlear electrode of a cochlear implant. In the past two decades, the eCAP has been widely recorded in both animals and clinical patient populations using different testing paradigms. This paper provides an overview of recording methodologies and response characteristics of the eCAP, as well as its potential applications in research and clinical situations. Relevant studies are reviewed and implications for clinicians are discussed.

  6. Temporal suppression and augmentation of click-evoked otoacoustic emissions

    DEFF Research Database (Denmark)

    Verhulst, Sarah; Harte, James; Dau, Torsten

    2008-01-01

    This study investigates and models temporal suppression of click-evoked otoacoustic emissions (CEOAEs). This suppression-effect is created when a suppressor-click is presented close in time to a test-click. The analysis was carried out for short time-frames of short- and long-latency CEOAEs...... suppression is present in all CEOAEs for inter-click intervals (ICIs) less than 8 ms. The long-latency CEOAEs showed augmentation (i.e., negative suppression) for ICIs of 6-7 ms which was not reported for the short-latency CEOAE at these ICIs. A phenomenological approach is adopted here to explain both...

  7. Estimation of evoked potentials using total least squares prony technique.

    Science.gov (United States)

    Akkin, T; Saliu, S

    1998-09-01

    The authors investigate the applicability of Prony modelling to the estimation of evoked potentials. Four types of total least squares (TLS) model are considered and their optimal parameters are defined based on ten visual averaged EPs. Simulations with various signal and noise characteristics show that the TLS-Prony estimation is superior to averaging for two of the models, namely the unconstrained and the stable models. Application of the TLS-Prony estimator as a post-processor to moderate averaging allows a reduction in the number of responses averaged, or equivalently of recording time, by a factor of two.

  8. Neuronal Rac1 is required for learning-evoked neurogenesis

    DEFF Research Database (Denmark)

    Haditsch, Ursula; Anderson, Matthew P; Freewoman, Julia

    2013-01-01

    Hippocampus-dependent learning and memory relies on synaptic plasticity as well as network adaptations provided by the addition of adult-born neurons. We have previously shown that activity-induced intracellular signaling through the Rho family small GTPase Rac1 is necessary in forebrain projection...... neurons for normal synaptic plasticity in vivo, and here we show that selective loss of neuronal Rac1 also impairs the learning-evoked increase in neurogenesis in the adult mouse hippocampus. Earlier work has indicated that experience elevates the abundance of adult-born neurons in the hippocampus...

  9. Heterologous corneal endothelial cell transplantation--human corneal endothelial cell transplantation in Lewis rats.

    OpenAIRE

    Tchah, H.

    1992-01-01

    A heterologous corneal endothelial transplantation was attempted using human endothelial cells and a Lewis rat penetrating keratoplasty model. Cultured human endothelial cells were seeded to a Lewis rat cornea, which was denuded of its endothelium. When grafted into the syngeneic Lewis rat, the graft remained clear for at least five days, and then became opaque and edematous because of immune rejection reaction. In contrast, corneas denuded of their endothelium became opaque and edematous imm...

  10. Endothelial Nitric Oxide Synthase Uncoupling: A Novel Pathway in OSA Induced Vascular Endothelial Dysfunction

    OpenAIRE

    Varadharaj, Saradhadevi; Porter, Kyle; Pleister, Adam; Wannemacher, Jacob; Sow, Angela; Jarjoura, David; Zweier, Jay L.; Khayat, Rami N.

    2014-01-01

    The mechanism of vascular endothelial dysfunction (VED) and cardiovascular disease in obstructive sleep apnea (OSA) is unknown. We performed a comprehensive evaluation of endothelial nitric oxide synthase (eNOS) function directly in the microcirculatory endothelial tissue of OSA patients who have very low cardiovascular risk status. Nineteen OSA patients underwent gluteal biopsies before, and after effective treatment of OSA. We measured superoxide (O2−·) and nitric oxide (NO) in the microcir...

  11. Vascular Endothelial Growth Factor from Embryonic Status to Cardiovascular Pathology

    Directory of Open Access Journals (Sweden)

    Mohsen Azimi-Nezhad

    2014-05-01

    Full Text Available Vascular endothelial growth factor (VEGF is a multifunctional cytokine with distinct functions in angiogenesis, lymphangiogenesis, vascular permeability, and hematopoiesis. VEGF is a highly conserved, disulfide-bonded dimeric glycoprotein of 34 to 45 kDa produced by several cell types including fibroblasts, neutrophils, endothelial cells, and peripheral blood mononuclear cells, particularly T lymphocytes and macrophages. Six VEGF isoforms are generated as a result of alternative splicing from a single VEGF gene, consisting of 121, 145, 165, 183, 189, or 206 amino acids. VEGF121, VEGF145, and VEGF165 are secreted whereas VEGF183, VEGF189, and VEGF206 are cell membrane-bound. VEGF145 has a key role during the vascularization of the human ovarian follicle and corpus luteum, in the placentation and embryonic periods, and in bone and wound healing, while VEGF165 is the most abundant and biologically active isoform. VEGF has been linked with a number of vascular pathologies including cardiovascular diseases such ischemic heart disease, heart failure, stroke, and diabetes and its related complications. In this review we aimed to present some important roles of VEGF in a number of clinical issues and indicate its involvement in several phenomena from the initial steps of the embryonic period to cardiovascular diseases.

  12. Separating common from distinctive variation.

    Science.gov (United States)

    van der Kloet, Frans M; Sebastián-León, Patricia; Conesa, Ana; Smilde, Age K; Westerhuis, Johan A

    2016-06-06

    Joint and individual variation explained (JIVE), distinct and common simultaneous component analysis (DISCO) and O2-PLS, a two-block (X-Y) latent variable regression method with an integral OSC filter can all be used for the integrated analysis of multiple data sets and decompose them in three terms: a low(er)-rank approximation capturing common variation across data sets, low(er)-rank approximations for structured variation distinctive for each data set, and residual noise. In this paper these three methods are compared with respect to their mathematical properties and their respective ways of defining common and distinctive variation. The methods are all applied on simulated data and mRNA and miRNA data-sets from GlioBlastoma Multiform (GBM) brain tumors to examine their overlap and differences. When the common variation is abundant, all methods are able to find the correct solution. With real data however, complexities in the data are treated differently by the three methods. All three methods have their own approach to estimate common and distinctive variation with their specific strength and weaknesses. Due to their orthogonality properties and their used algorithms their view on the data is slightly different. By assuming orthogonality between common and distinctive, true natural or biological phenomena that may not be orthogonal at all might be misinterpreted.

  13. Influenza Virus Infection Induces Platelet-Endothelial Adhesion Which Contributes to Lung Injury.

    Science.gov (United States)

    Sugiyama, Michael G; Gamage, Asela; Zyla, Roman; Armstrong, Susan M; Advani, Suzanne; Advani, Andrew; Wang, Changsen; Lee, Warren L

    2015-12-04

    recently shown that the virus can infect human lung endothelial cells, but the functional consequences of this infection are unknown (S. M. Armstrong, C. Wang, J. Tigdi, X. Si, C. Dumpit, S. Charles, A. Gamage, T. J. Moraes, and W. L. Lee, PLoS One 7:e47323, 2012, http://dx.doi.org/10.1371/journal.pone.0047323). Here, we show that this infection causes platelets to adhere to the lung endothelium. Importantly, blocking platelets using two distinct antiplatelet drugs improved survival in a mouse model of severe influenza infection. Thus, platelet inhibition may constitute a novel therapeutic strategy to improve the host response to severe infections with influenza. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  14. Heterogeneity in Neutrophil Microparticles Reveals Distinct Proteome and Functional Properties*

    Science.gov (United States)

    Dalli, Jesmond; Montero-Melendez, Trinidad; Norling, Lucy V; Yin, Xiaoke; Hinds, Charles; Haskard, Dorian; Mayr, Manuel; Perretti, Mauro

    2013-01-01

    Altered plasma neutrophil microparticle levels have recently been implicated in a number of vascular and inflammatory diseases, yet our understanding of their actions is very limited. Herein, we investigate the proteome of neutrophil microparticles in order to shed light on their biological actions. Stimulation of human neutrophils, either in suspension or adherent to an endothelial monolayer, led to the production of microparticles containing >400 distinct proteins with only 223 being shared by the two subsets. For instance, postadherent microparticles were enriched in alpha-2 macroglobulin and ceruloplasmin, whereas microparticles produced by neutrophils in suspension were abundant in heat shock 70 kDa protein 1. Annexin A1 and lactotransferrin were expressed in both microparticle subsets. We next determined relative abundance of these proteins in three types of human microparticle samples: healthy volunteer plasma, plasma of septic patients and skin blister exudates finding that these proteins were differentially expressed on neutrophil microparticles from these samples reflecting in part the expression profiles we found in vitro. Functional assessment of the neutrophil microparticles subsets demonstrated that in response to direct stimulation neutrophil microparticles produced reactive oxygen species and leukotriene B4 as well as locomoted toward a chemotactic gradient. Finally, we investigated the actions of the two neutrophil microparticles subsets described herein on target cell responses. Microarray analysis with human primary endothelial cells incubated with either microparticle subset revealed a discrete modulation of endothelial cell gene expression profile. These findings demonstrate that neutrophil microparticles are heterogenous and can deliver packaged information propagating the activation status of the parent cell, potentially exerting novel and fundamental roles both under homeostatic and disease conditions. PMID:23660474

  15. [Corneal endothelial decompensation of iridocorneal endothelial syndrome treated by penetrating keratoplasty].

    Science.gov (United States)

    Chen, J; Liu, Z; Yu, L

    1996-07-01

    To evaluate the effect of penetrating keratoplasty in treatment of iridocorneal endothelial syndrome. The clinical and pathologic evaluation records were retrospectively analyzed for 8 cases with iridocorneal endothelial syndrome treated by penetrating keratoplasty. Postoperatively, they were followed for 3 months to 6 years. Seven cases had visual improvement, five buttons kept being transparent and three buttons became opaque. The penetrating keratoplasty is an effective measure for treatment of corneal endothelial decompensation of iridocorneal endothelial syndrome. However, the successful operative rate of this syndrome is lower than that in cases with corneal leucoma without vascularization.

  16. Leukocytes Breach Endothelial Barriers by Insertion of Nuclear Lobes and Disassembly of Endothelial Actin Filaments

    Directory of Open Access Journals (Sweden)

    Sagi Barzilai

    2017-01-01

    Full Text Available The endothelial cytoskeleton is a barrier for leukocyte transendothelial migration (TEM. Mononuclear and polymorphonuclear leukocytes generate gaps of similar micron-scale size when squeezing through inflamed endothelial barriers in vitro and in vivo. To elucidate how leukocytes squeeze through these barriers, we co-tracked the endothelial actin filaments and leukocyte nuclei in real time. Nuclear squeezing involved either preexistent or de novo-generated lobes inserted into the leukocyte lamellipodia. Leukocyte nuclei reversibly bent the endothelial actin stress fibers. Surprisingly, formation of both paracellular gaps and transcellular pores by squeezing leukocytes did not require Rho kinase or myosin II-mediated endothelial contractility. Electron-microscopic analysis suggested that nuclear squeezing displaced without condensing the endothelial actin filaments. Blocking endothelial actin turnover abolished leukocyte nuclear squeezing, whereas increasing actin filament density did not. We propose that leukocyte nuclei must disassemble the thin endothelial actin filaments interlaced between endothelial stress fibers in order to complete TEM.

  17. The CXC Chemokine-degrading Protease SpyCep of Streptococcus pyogenes Promotes Its Uptake into Endothelial Cells*

    Science.gov (United States)

    Kaur, Simran Jeet; Nerlich, Andreas; Bergmann, Simone; Rohde, Manfred; Fulde, Marcus; Zähner, Dorothea; Hanski, Emanuel; Zinkernagel, Annelies; Nizet, Victor; Chhatwal, Gursharan S.; Talay, Susanne R.

    2010-01-01

    Streptococcus pyogenes expresses the LPXTG motif-containing cell envelope serine protease SpyCep (also called ScpC, PrtS) that degrades and inactivates the major chemoattractant interleukin 8 (IL-8), thereby impairing host neutrophil recruitment. In this study, we identified a novel function of SpyCep: the ability to mediate uptake into primary human endothelial cells. SpyCep triggered its uptake into endothelial cells but not into human epithelial cells originating from pharynx or lung, indicating an endothelial cell-specific uptake mechanism. SpyCep mediated cellular invasion by an endosomal/lysosomal pathway distinct from the caveolae-mediated invasion pathway of S. pyogenes. Recombinant expression and purification of proteolytically active SpyCep and a series of subfragments allowed functional dissection of the domains responsible for endothelial cell invasion and IL-8 degradation. The N-terminal PR domain was sufficient to mediate endothelial cell invasion, whereas for IL-8-degrading activity, the protease domain and the flanking A domain were required. A polyclonal rabbit serum raised against the recombinant protease efficiently blocked the invasion-mediating activity of SpyCep but not its proteolytic function, further indicating that SpyCep-mediated internalization is independent from its enzymatic activity. SpyCep may thus specifically mediate its own uptake as secreted protein into human endothelial cells. PMID:20562101

  18. The CXC chemokine-degrading protease SpyCep of Streptococcus pyogenes promotes its uptake into endothelial cells.

    Science.gov (United States)

    Kaur, Simran Jeet; Nerlich, Andreas; Bergmann, Simone; Rohde, Manfred; Fulde, Marcus; Zähner, Dorothea; Hanski, Emanuel; Zinkernagel, Annelies; Nizet, Victor; Chhatwal, Gursharan S; Talay, Susanne R

    2010-09-03

    Streptococcus pyogenes expresses the LPXTG motif-containing cell envelope serine protease SpyCep (also called ScpC, PrtS) that degrades and inactivates the major chemoattractant interleukin 8 (IL-8), thereby impairing host neutrophil recruitment. In this study, we identified a novel function of SpyCep: the ability to mediate uptake into primary human endothelial cells. SpyCep triggered its uptake into endothelial cells but not into human epithelial cells originating from pharynx or lung, indicating an endothelial cell-specific uptake mechanism. SpyCep mediated cellular invasion by an endosomal/lysosomal pathway distinct from the caveolae-mediated invasion pathway of S. pyogenes. Recombinant expression and purification of proteolytically active SpyCep and a series of subfragments allowed functional dissection of the domains responsible for endothelial cell invasion and IL-8 degradation. The N-terminal PR domain was sufficient to mediate endothelial cell invasion, whereas for IL-8-degrading activity, the protease domain and the flanking A domain were required. A polyclonal rabbit serum raised against the recombinant protease efficiently blocked the invasion-mediating activity of SpyCep but not its proteolytic function, further indicating that SpyCep-mediated internalization is independent from its enzymatic activity. SpyCep may thus specifically mediate its own uptake as secreted protein into human endothelial cells.

  19. Leptospira interrogans causes quantitative and morphological disturbances in adherens junctions and other biological groups of proteins in human endothelial cells

    Science.gov (United States)

    Sato, Hiromi

    2017-01-01

    Pathogenic Leptospira transmits from animals to humans, causing the zoonotic life-threatening infection called leptospirosis. This infection is reported worldwide with higher risk in tropical regions. Symptoms of leptospirosis range from mild illness to severe illness such as liver damage, kidney failure, respiratory distress, meningitis, and fatal hemorrhagic disease. Invasive species of Leptospira rapidly disseminate to multiple tissues where this bacterium damages host endothelial cells, increasing vascular permeability. Despite the burden in humans and animals, the pathogenic mechanisms of Leptospira infection remain to be elucidated. The pathogenic leptospires adhere to endothelial cells and permeabilize endothelial barriers in vivo and in vitro. In this study, human endothelial cells were infected with the pathogenic L. interrogans serovar Copenhageni or the saprophyte L. biflexa serovar Patoc to investigate morphological changes and other distinctive phenotypes of host cell proteins by fluorescence microscopy. Among those analyzed, 17 proteins from five biological classes demonstrated distinctive phenotypes in morphology and/or signal intensity upon infection with Leptospira. The affected biological groups include: 1) extracellular matrix, 2) intercellular adhesion molecules and cell surface receptors, 3) intracellular proteins, 4) cell-cell junction proteins, and 5) a cytoskeletal protein. Infection with the pathogenic strain most profoundly disturbed the biological structures of adherens junctions (VE-cadherin and catenins) and actin filaments. Our data illuminate morphological disruptions and reduced signals of cell-cell junction proteins and filamentous actin in L. interrogans-infected endothelial cells. In addition, Leptospira infection, regardless of pathogenic status, influenced other host proteins belonging to multiple biological classes. Our data suggest that this zoonotic agent may damage endothelial cells via multiple cascades or pathways

  20. Leptospira interrogans causes quantitative and morphological disturbances in adherens junctions and other biological groups of proteins in human endothelial cells.

    Directory of Open Access Journals (Sweden)

    Hiromi Sato

    2017-07-01

    Full Text Available Pathogenic Leptospira transmits from animals to humans, causing the zoonotic life-threatening infection called leptospirosis. This infection is reported worldwide with higher risk in tropical regions. Symptoms of leptospirosis range from mild illness to severe illness such as liver damage, kidney failure, respiratory distress, meningitis, and fatal hemorrhagic disease. Invasive species of Leptospira rapidly disseminate to multiple tissues where this bacterium damages host endothelial cells, increasing vascular permeability. Despite the burden in humans and animals, the pathogenic mechanisms of Leptospira infection remain to be elucidated. The pathogenic leptospires adhere to endothelial cells and permeabilize endothelial barriers in vivo and in vitro. In this study, human endothelial cells were infected with the pathogenic L. interrogans serovar Copenhageni or the saprophyte L. biflexa serovar Patoc to investigate morphological changes and other distinctive phenotypes of host cell proteins by fluorescence microscopy. Among those analyzed, 17 proteins from five biological classes demonstrated distinctive phenotypes in morphology and/or signal intensity upon infection with Leptospira. The affected biological groups include: 1 extracellular matrix, 2 intercellular adhesion molecules and cell surface receptors, 3 intracellular proteins, 4 cell-cell junction proteins, and 5 a cytoskeletal protein. Infection with the pathogenic strain most profoundly disturbed the biological structures of adherens junctions (VE-cadherin and catenins and actin filaments. Our data illuminate morphological disruptions and reduced signals of cell-cell junction proteins and filamentous actin in L. interrogans-infected endothelial cells. In addition, Leptospira infection, regardless of pathogenic status, influenced other host proteins belonging to multiple biological classes. Our data suggest that this zoonotic agent may damage endothelial cells via multiple cascades or

  1. Cataract phacoemulsification and corneal endothelial cell damage

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    Ni Zhu

    2013-07-01

    Full Text Available Phacoemulsification with small incision, reduced number of inflammation cells, and better postoperative recovery has been recognized as the world's most popular option for cataract surgery. Modern cataract surgery is developing gradually from sight rehabilitating to refractive surgery with better vision acuity. Being the most important part of the eye refractive system, maintenance of the cornea's transparency relies heavily upon the healthy endothelial cells. It is well known that there will be endothelial cell loss after phacoemulsification and the damage of the endothelial cells may lead to corneal swellings and opacity, or even the corneal descompensation, which often severely influenced the postoperative vision recovery. This is a review of phacoemulsification and the risk factors of corneal endothelial damage pre-and postoperation.

  2. Apicobasal polarity of brain endothelial cells.

    Science.gov (United States)

    Worzfeld, Thomas; Schwaninger, Markus

    2016-02-01

    Normal brain homeostasis depends on the integrity of the blood-brain barrier that controls the access of nutrients, humoral factors, and immune cells to the CNS. The blood-brain barrier is composed mainly of brain endothelial cells. Forming the interface between two compartments, they are highly polarized. Apical/luminal and basolateral/abluminal membranes differ in their lipid and (glyco-)protein composition, allowing brain endothelial cells to secrete or transport soluble factors in a polarized manner and to maintain blood flow. Here, we summarize the basic concepts of apicobasal cell polarity in brain endothelial cells. To address potential molecular mechanisms underlying apicobasal polarity in brain endothelial cells, we draw on investigations in epithelial cells and discuss how polarity may go awry in neurological diseases. © The Author(s) 2015.

  3. Bacteria and endothelial cells: a toxic relationship.

    Science.gov (United States)

    Lubkin, Ashira; Torres, Victor J

    2017-02-01

    Pathogenic bacteria use the bloodstream as a highway for getting around the body, and thus have to find ways to enter and exit through the endothelium. Many bacteria approach this problem by producing toxins that can breach the endothelial barrier through diverse creative mechanisms, including directly killing endothelial cells (ECs), weakening the cytoskeleton within ECs, and breaking the junctions between ECs. Toxins can also modulate the immune response by influencing endothelial biology, and can modulate endothelial function by influencing the response of leukocytes. Understanding these interactions, in both the in vitro and in vivo contexts, is of critical importance for designing new therapies for sepsis and other severe bacterial diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Specular Microscopic Features of Corneal Endothelial Vacuolation

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    Mozhgan Rezaei Kanavi

    2011-01-01

    Full Text Available Purpose: To introduce a specular microscopic reference image for endothelial vacuolation in donated corneas. Methods: Two corneas from a donor with diffuse, round to oval dark areas at the endothelial level on slit lamp biomicroscopy and one normal-appearing donor cornea underwent specular microscopy, histopathologic evaluation and transmission electron microscopy. Results: Specular microscopy of the two corneas with abnormal-looking endothelium revealed large numbers of dark, round to oval structures within the endothelium in favor of endothelial vacuolation. Light microscopy disclosed variable sized cyst-like structures within the cytoplasm. Transmission electron microscopy showed electronlucent and relatively large-sized intracytoplasmic vacuoles. These features were not observed in the endothelium of the normal cornea. Conclusion: The specular microscopic features of endothelial vacuolation in donated corneas were confirmed by light microscopy and transmission electron microscopy, therefore the specular image may be proposed as a reference to eye banks.

  5. Endothelial replacement: the limbal pocket approach.

    Science.gov (United States)

    Terry, Mark A

    2003-03-01

    The limbal pocket approach to endothelial replacement shows extraordinary promise in fulfilling the ideal goals of surgical treatment for endothelial dysfunction. From its inception, DLEK surgery has demonstrated that, by preserving the limbus and eliminating surface corneal incisions and sutures, the corneal topography can be stabilized with little change from preoperative measurements of astigmatism and corneal power. The surgical dissection planes of DLEK surgery are inherently stronger than that of PK or any other form of endothelial replacement, allowing early stability of the refraction and making the eye safer from blunt trauma over the long term. Further work with DLEK must be performed in perfecting the optical properties of the stromal interface before this technique can be used widely; however, as technology and techniques improve, DLEK surgery holds the promise of being the ideal method for endothelial replacement in the 21st century.

  6. Clinical application of visual evoked potential in orbital cellulitis of infants

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    Xiao-Juan Jing

    2014-07-01

    Full Text Available AIM: To explore the visual evoked potential in infantile orbital cellulitis' clinical applications by monitoring the visual evoked potential changes in infantile orbital cellulitis before, during and after treatment.METHODS: Twenty-three cases of CT diagnosed single orbital cellulitis were examined by the visual evoked potentials. The affected eyes as observation group, and healthy eyes as control group. Comparative observation of visual evoked potential changes in amplitude and incubation period before, during and after the treatment. RESULTS: Compared with the control group, the observation group's visual evoked potential changes included reduced amplitude, extended incubation period. With the treatment progress, the observation group had gradual increase in amplitude, gradual reduction in incubation period. CONCLUSION: In infantile orbital cellulitis, the use of visual evoked potentials is a simple, feasible and effective method to monitoring the visual function during the treatment.

  7. Magnetic fields evoked by speech sounds in preschool children.

    Science.gov (United States)

    Pihko, Elina; Kujala, Teija; Mickos, Annika; Antell, Henrik; Alku, Paavo; Byring, Roger; Korkman, Marit

    2005-01-01

    Our objective was to study how well the auditory evoked magnetic fields (EF) reflect the behavioral discrimination of speech sounds in preschool children, and if they reveal the same information as simultaneously recorded evoked potentials (EP). EFs and EPs were recorded in 11 preschool children (mean age 6 years 9 months) using an oddball paradigm with two sets of speech stimuli consisting both of one standard and two deviants. After the brain activity recording, children were tested on behavioural discrimination of the same stimuli presented in pairs. There was a mismatch negativity (MMN) calculated from difference curves and its magnetic counterpart MMNm measured from the original responses only to those deviants, which were behaviourally easiest to discriminate from the standards. In addition, EF revealed significant differences between the locations of the activation depending on the hemisphere and stimulus properties. EF, in addition to reflecting the sound-discrimination accuracy in a similar manner as EP, also reflected the spatial differences in activation of the temporal lobes. These results suggest that both EPs and EFs are feasible for investigating the neural basis of sound discrimination in young children. The recording of EFs with its high spatial resolution reveals information on the location of the activated neural sources.

  8. A New Measure for Monitoring Intraoperative Somatosensory Evoked Potentials

    Science.gov (United States)

    Jin, Seung-Hyun; Kim, Jeong Eun; Choi, Young Doo

    2014-01-01

    Objective To propose a new measure for effective monitoring of intraoperative somatosensory evoked potentials (SEP) and to validate the feasibility of this measure for evoked potentials (EP) and single trials with a retrospective data analysis study. Methods The proposed new measure (hereafter, a slope-measure) was defined as the relative slope of the amplitude and latency at each EP peak compared to the baseline value, which is sensitive to the change in the amplitude and latency simultaneously. We used the slope-measure for EP and single trials and compared the significant change detection time with that of the conventional peak-to-peak method. When applied to single trials, each single trial signal was processed with optimal filters before using the slope-measure. In this retrospective data analysis, 7 patients who underwent cerebral aneurysm clipping surgery for unruptured aneurysm middle cerebral artery (MCA) bifurcation were included. Results We found that this simple slope-measure has a detection time that is as early or earlier than that of the conventional method; furthermore, using the slope-measure in optimally filtered single trials provides warning signs earlier than that of the conventional method during MCA clipping surgery. Conclusion Our results have confirmed the feasibility of the slope-measure for intraoperative SEP monitoring. This is a novel study that provides a useful measure for either EP or single trials in intraoperative SEP monitoring. PMID:25628803

  9. A wireless system for monitoring transcranial motor evoked potentials.

    Science.gov (United States)

    Farajidavar, Aydin; Seifert, Jennifer L; Bell, Jennifer E S; Seo, Young-Sik; Delgado, Mauricio R; Sparagana, Steven; Romero, Mario I; Chiao, J-C

    2011-01-01

    Intraoperative neurophysiological monitoring (IONM) is commonly used as an attempt to minimize neurological morbidity from operative manipulations. The goal of IONM is to identify changes in the central and peripheral nervous system function prior to irreversible damage. Intraoperative monitoring also has been effective in localizing anatomical structures, including peripheral nerves and sensorimotor cortex, which helps guide the surgeon during dissection. As part of IONM, transcranial motor evoked potentials (TcMEPs), and somatosensory evoked potentials (SSEPs) are routinely monitored. However, current wired systems are cumbersome as the wires contribute to the crowded conditions in the operating room and in doing so not only it limits the maneuverability of the surgeon and assistants, but also places certain demand in the total anesthesia required during surgery, due to setup preoperative time needed for proper electrode placement, due to the number and length of the wires, and critical identification of the lead wires needed for stimulation and recording. To address these limitations, we have developed a wireless TcMEP IONM system as a first step toward a multimodality IONM system. Bench-top and animal experiments in rodents demonstrated that the wireless method reproduced with high fidelity, and even increased the frequency bandwidth of the TcMEP signals, compared to wired systems. This wireless system will reduce the preoperative time required for IONM setup, add convenience for surgical staff, and reduce wire-related risks for patients during the operation.

  10. Evoked brain potentials and disability in brain-damaged patients.

    Science.gov (United States)

    Rappaport, M; Hall, K; Hopkins, K; Belleza, T; Berrol, S; Reynolds, G

    1977-08-01

    Various measures of evoked brain potential abnormality (EPA) were correlated with disability ratings (DR) for 35 brain-damaged patients. EPA data consisted of judgements of abnormality of ipsilateral, contralateral and bilateral responses to auditory and visual stimuli reflecting activity in the brain stem, subcortex and cortex. DR data were obtained from a scale developed for this study to quantize and categorize patients with a wide range of disabilities from coma to normal functioning. EPA scores based on visual and auditory cortical responses showed significantly positive correlations with degree of disability. Visual response correlation was .49, auditory .38 and combined visual and auditory .51. It was concluded that EPA measures can reflect disability independently of clinical information. They are useful in assessing brain function in general and, specifically, in assessing impairment of sensory function. The evoked potential technique was particularly useful in patients who were not able to participate fully in their own examination. There were indications that the technique may also be valuable in monitoring progress and in predicting clinical outcome in brain-damaged patients.

  11. Characteristics and clinical applications of ocular vestibular evoked myogenic potentials.

    Science.gov (United States)

    Kantner, C; Gürkov, R

    2012-12-01

    Recently, ocular vestibular evoked myogenic potentials (oVEMPs) have been described and added to the neuro-otologic test battery as a new measure for the vestibulo-ocular reflex. oVEMPs represent extraocular muscle activity in response to otolith stimulation e.g. by air-conducted sound or bone-conducted vibration. In response to vestibular stimulation, electromyographic activity of the extraocular muscles can be recorded by means of surface electrodes placed beneath the contralateral eye. oVEMPs are likely to reflect predominantly utricular function, while the widely established cervical vestibular evoked myogenic potentials (cVEMPs) assess saccular function. Thus, measuring oVEMPs and cVEMPs in addition to caloric and head impulse testing provides further evaluation of the vestibular system and enables quick and cost-effective assessment of otolith function. This review summarizes the neurophysiological properties of oVEMPs, gives recommendations for recording conditions and discusses oVEMP alterations in various disorders of the vestibular system. With increasing insight into oVEMP characteristics in vestibular disorders, e.g. Menière's disease and superior semicircular canal dehiscence syndrome, oVEMPs are becoming a promising new diagnostic tool for evaluating utricular function. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Somatosensory evoked potentials in children with severe head trauma.

    Science.gov (United States)

    Schalamon, Johannes; Singer, Georg; Kurschel, Senta; Höllwarth, Michael E

    2005-07-01

    We evaluated the predictive value of somatosensory evoked potentials (SEP) in a series of children with severe traumatic brain injury (TBI). The prospective clinical investigation was performed in a Level I paediatric trauma centre. We included 26 consecutive comatose paediatric patients aged from 1 month to 17 years (median age 11 years) following severe TBI (initial Glasgow Coma Score (GCS) 8 or below). Besides SEP recordings, the intracranial pressure and the results of an initial cranial CT scan were filed. The Glasgow Outcome Scale (GOS) was used to assess outcome at discharge. Thirteen children had normal SEP measurements, three patients had abnormal SEP recordings and a cortical response was bilaterally absent in ten children. Out of 26 children, 10 died whereas two remained in a persistent vegetative state. Only one child suffered from significant neurological deficits (GOS 3) at discharge. Seven patients survived with a GOS of 4 and six children survived without neurological impairment (GOS 5). Normal SEP indicated a favourable outcome in most children but did not rule out the occurrence of death, while absence of SEP was related to unfavourable outcome in all cases. Measurement of somatosensory evoked potentials provides valuable data for determining the prognosis at early coma stages. Our data show that an unfavourable outcome can be predicted with higher precision than a favourable outcome.

  13. Unwanted sexual experiences and cognitive appraisals that evoke mental contamination.

    Science.gov (United States)

    Ishikawa, Ryotaro; Kobori, Osamu; Shimizu, Eiji

    2015-01-01

    Mental contamination is a psychological sense of contamination that involves an internal, emotional feeling of dirtiness that may be evoked by unwanted thoughts and images, such as sexual assaults. This study aimed to investigate which types of unwanted sexual experiences evoke the strongest mental contamination, and to test the hypothesis that cognitive appraisals of an unwanted sexual experience predict indices of mental contamination (i.e. feeling of dirtiness, urge to wash, internal negative emotions, and external negative emotions). 148 female participants were asked to recall their most distressing unwanted sexual experiences. Indices of mental contamination and cognitive appraisals of the experience were then assessed. Our findings indicated that individuals recalling experiences related to rape felt more intense feelings of dirtiness than individuals recalling other types of unwanted sexual experience, such as verbal sexual assault, visual sexual assault, and forcible touching/frottage. In addition, hierarchical regression analyses demonstrated that a cognitive appraisal of perceived violation predicted all of the indices of mental contamination after controlling anxiety, depression, and fear of contact contamination. The present study demonstrated that an individual is at greatest risk of mental contamination if she has experienced rape/attempted rape, and if she makes a cognitive appraisal of violation regarding the incident.

  14. Synaptically evoked glutamate transporter currents in Spinal Dorsal Horn Astrocytes

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    Dougherty Patrick M

    2009-07-01

    Full Text Available Abstract Background Removing and sequestering synaptically released glutamate from the extracellular space is carried out by specific plasma membrane transporters that are primarily located in astrocytes. Glial glutamate transporter function can be monitored by recording the currents that are produced by co-transportation of Na+ ions with the uptake of glutamate. The goal of this study was to characterize glutamate transporter function in astrocytes of the spinal cord dorsal horn in real time by recording synaptically evoked glutamate transporter currents. Results Whole-cell patch clamp recordings were obtained from astrocytes in the spinal substantia gelatinosa (SG area in spinal slices of young adult rats. Glutamate transporter currents were evoked in these cells by electrical stimulation at the spinal dorsal root entry zone in the presence of bicuculline, strychnine, DNQX and D-AP5. Transporter currents were abolished when synaptic transmission was blocked by TTX or Cd2+. Pharmacological studies identified two subtypes of glutamate transporters in spinal astrocytes, GLAST and GLT-1. Glutamate transporter currents were graded with stimulus intensity, reaching peak responses at 4 to 5 times activation threshold, but were reduced following low-frequency (0.1 – 1 Hz repetitive stimulation. Conclusion These results suggest that glutamate transporters of spinal astrocytes could be activated by synaptic activation, and recording glutamate transporter currents may provide a means of examining the real time physiological responses of glial cells in spinal sensory processing, sensitization, hyperalgesia and chronic pain.

  15. Nostalgia-Evoked Inspiration: Mediating Mechanisms and Motivational Implications.

    Science.gov (United States)

    Stephan, Elena; Sedikides, Constantine; Wildschut, Tim; Cheung, Wing-Yee; Routledge, Clay; Arndt, Jamie

    2015-10-01

    Six studies examined the nostalgia-inspiration link and its motivational implications. In Study 1, nostalgia proneness was positively associated with inspiration frequency and intensity. In Studies 2 and 3, the recollection of nostalgic (vs. ordinary) experiences increased both general inspiration and specific inspiration to engage in exploratory activities. In Study 4, serial mediational analyses supported a model in which nostalgia increases social connectedness, which subsequently fosters self-esteem, which then boosts inspiration. In Study 5, a rigorous evaluation of this serial mediational model (with a novel nostalgia induction controlling for positive affect) reinforced the idea that nostalgia-elicited social connectedness increases self-esteem, which then heightens inspiration. Study 6 extended the serial mediational model by demonstrating that nostalgia-evoked inspiration predicts goal pursuit (intentions to pursue an important goal). Nostalgia spawns inspiration via social connectedness and attendant self-esteem. In turn, nostalgia-evoked inspiration bolsters motivation. © 2015 by the Society for Personality and Social Psychology, Inc.

  16. Visual evoked potentials, reaction times and eye dominance in cricketers.

    Science.gov (United States)

    Thomas, N G; Harden, L M; Rogers, G G

    2005-09-01

    Few studies have examined the physiology of cricket, including the difference in ability between batsmen to make controlled contact with a ball bowled at high speed. We therefore measured visual evoked potentials and choice reaction times with dominant eyes, non-dominant eyes, and both eyes together, in 15 elite batsmen and 10 elite bowlers (aged 20.9 SD 1.9 years) and 9 control subjects (aged 20.2 SD 1.5 years). The latency and amplitude of waves N70, P100 and N145 were determined for each visual evoked potential (VEP). In addition interpeak latencies and peak to peak amplitudes were measured. The subjects also completed a choice reaction test to a visual stimulus. We found that cricketers were not more likely to have crossed dominance (dominant eye contralateral to dominant hand) than controls. Cricketers had a faster latency for VEP wave N70 than controls (p=0.03). However reaction time was not different between cricketers and the control group. Across all subjects, in comparison to monocular testing, binocular testing led to a faster choice reaction time (p=0.02) and larger amplitudes of VEP wave N70 (p=0.01). Visual processing during the first 100(-1)50 ms of the balls flight together with binocular vision facilitates retinal activation in talented cricketers.

  17. [Endothelial dysfunction in pathogenesis of duodenal ulcer].

    Science.gov (United States)

    Oparin, A G; Oparin, A A

    2002-01-01

    It is shown that in patients with ulcer associated with Helicobacter pylori (HP) there is a close correlation between the severity of the lesion of gastroduodenal protective mucous barrier and that of endothelial dysfunction manifesting in elevated level of endothelin-1, serum levels of TBK-active products, inhibition of blood flow and narrowing of the celiac trunk. The correlation becomes stronger with expanding contamination of gastroduodenal mucosa with HP. Thus, HP may participate in breaking the protective mucous barrier in endothelial dysfunction.

  18. Endothelial microparticles: Sophisticated vesicles modulating vascular function

    Science.gov (United States)

    Curtis, Anne M; Edelberg, Jay; Jonas, Rebecca; Rogers, Wade T; Moore, Jonni S; Syed, Wajihuddin; Mohler, Emile R

    2015-01-01

    Endothelial microparticles (EMPs) belong to a family of extracellular vesicles that are dynamic, mobile, biological effectors capable of mediating vascular physiology and function. The release of EMPs can impart autocrine and paracrine effects on target cells through surface interaction, cellular fusion, and, possibly, the delivery of intra-vesicular cargo. A greater understanding of the formation, composition, and function of EMPs will broaden our understanding of endothelial communication and may expose new pathways amenable for therapeutic manipulation. PMID:23892447

  19. Defining poverty as distinctively human

    Directory of Open Access Journals (Sweden)

    H.P.P. Lötter

    2007-05-01

    Full Text Available While it is relatively easy for most people to identify human beings suffering from poverty, it is rather more difficult to come to a proper understanding of poverty. In this article the author wants to deepen our understanding of poverty by interpreting the conventional definitions of poverty in a new light. The article starts with a defence of a claim that poverty is a concept uniquely applicable to humans. It then present a critical discussion of the distinction between absolute and relative poverty and it is then argued that a revision of this distinction can provide general standards applicable to humans everywhere.

  20. Distinct Patterns of Temporal and Directional Connectivity among Intrinsic Networks in the Human Brain.

    Science.gov (United States)

    Shine, James M; Kucyi, Aaron; Foster, Brett L; Bickel, Stephan; Wang, Danhong; Liu, Hesheng; Poldrack, Russell A; Hsieh, Liang-Tien; Hsiang, Jen Chun; Parvizi, Josef

    2017-10-04

    To determine the spatiotemporal relationships among intrinsic networks of the human brain, we recruited seven neurosurgical patients (four males and three females) who were implanted with intracranial depth electrodes. We first identified canonical resting-state networks at the individual subject level using an iterative matching procedure on each subject's resting-state fMRI data. We then introduced single electrical pulses to fMRI pre-identified nodes of the default network (DN), frontoparietal network (FPN), and salience network (SN) while recording evoked responses in other recording sites within the same networks. We found bidirectional signal flow across the three networks, albeit with distinct patterns of evoked responses within different time windows. We used a data-driven clustering approach to show that stimulation of the FPN and SN evoked a rapid (130 ms) in other nodes of the DN, as well as FPN and SN. Our results provide temporal information about the patterns of signal flow between intrinsic networks that provide insights into the spatiotemporal dynamics that are likely to constrain the architecture of the brain networks supporting human cognition and behavior. SIGNIFICANCE STATEMENT Despite great progress in the functional neuroimaging of the human brain, we still do not know the precise set of rules that define the patterns of temporal organization between large-scale networks of the brain. In this study, we stimulated and then recorded electrical evoked potentials within and between three large-scale networks of the brain, the default network (DN), frontoparietal network (FPN), and salience network (SN), in seven subjects undergoing invasive neurosurgery. Using a data-driven clustering approach, we observed distinct temporal and directional patterns between the three networks, with FPN and SN activity predominant in early windows and DN stimulation affecting the network in later windows. These results provide important temporal information about

  1. Endothelial Dysfunction in Chronic Inflammatory Diseases

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    Curtis M. Steyers

    2014-06-01

    Full Text Available Chronic inflammatory diseases are associated with accelerated atherosclerosis and increased risk of cardiovascular diseases (CVD. As the pathogenesis of atherosclerosis is increasingly recognized as an inflammatory process, similarities between atherosclerosis and systemic inflammatory diseases such as rheumatoid arthritis, inflammatory bowel diseases, lupus, psoriasis, spondyloarthritis and others have become a topic of interest. Endothelial dysfunction represents a key step in the initiation and maintenance of atherosclerosis and may serve as a marker for future risk of cardiovascular events. Patients with chronic inflammatory diseases manifest endothelial dysfunction, often early in the course of the disease. Therefore, mechanisms linking systemic inflammatory diseases and atherosclerosis may be best understood at the level of the endothelium. Multiple factors, including circulating inflammatory cytokines, TNF-α (tumor necrosis factor-α, reactive oxygen species, oxidized LDL (low density lipoprotein, autoantibodies and traditional risk factors directly and indirectly activate endothelial cells, leading to impaired vascular relaxation, increased leukocyte adhesion, increased endothelial permeability and generation of a pro-thrombotic state. Pharmacologic agents directed against TNF-α-mediated inflammation may decrease the risk of endothelial dysfunction and cardiovascular disease in these patients. Understanding the precise mechanisms driving endothelial dysfunction in patients with systemic inflammatory diseases may help elucidate the pathogenesis of atherosclerosis in the general population.

  2. Calcium handling in porcine coronary endothelial cells by gastrin-17.

    Science.gov (United States)

    Grossini, E; Molinari, C; Sigaudo, L; Biella, M; Mary, D A S G; Vacca, G

    2013-04-01

    In porcine coronary artery endothelial cells (PCAEC), gastrin-17 has recently been found to increase nitric oxide (NO) production by the endothelial NO synthase (eNOS) isoform through cholecystokinin 1/2 (CCK1/2) receptors and the involvement of protein kinase A (PKA), PKC and the β2-adrenoreceptor-related pathway. As eNOS is the Ca(2)(+)-dependent isoform of the enzyme, we aimed to examine the effects of gastrin-17 on Ca(2)(+) movements. Thus, experiments were performed in Fura-2-acetoxymethyl-ester-loaded PCAEC, where changes of cytosolic Ca(2)(+) ([Ca(2)(+)]c) caused by gastrin-17 were analysed and compared with those of CCK receptors and β2-adrenoreceptors agonists/antagonists. In addition, some experiments were performed by stimulating cells with gastrin-17 in the presence or absence of cAMP/PKA activator/inhibitor and of phospholipase C (PLC) and Ca(2)(+)-calmodulin dependent protein kinase II (CaMKII) blockers. The results have shown that gastrin-17 can promote a transient increase in [Ca(2)(+)]c mainly originating from an intracellular pool sensitive to thapsigargin and from the extracellular space. In addition, the response of cells to gastrin-17 was increased by the adenylyl cyclase activator and the β2-adrenoreceptor agonists and affected mainly by the CCK2 receptor agonists/antagonists. Moreover, the effects of gastrin-17 were prevented by β2-adrenoreceptors and CaMKII blockers and the adenylyl cyclase/PKA and PLC inhibitors. Finally, in PCAEC cultured in Na(+)-free medium or loaded with the plasma membrane Ca(2)(+) pump inhibitor, the gastrin-17-evoked Ca(2)(+) transient was long lasting. In conclusion, this study shows that gastrin-17 affected intracellular Ca(2)(+) homeostasis in PCAEC by both promoting a discharge of an intracellular pool and by interfering with the operation of store-dependent channels through mainly CCK2 receptors and PKA/PLC- and CaMKII-related signalling downstream of β2-adrenoreceptor stimulation.

  3. C1q/TNF-Related Protein-9 Ameliorates Ox-LDL-Induced Endothelial Dysfunction via PGC-1α/AMPK-Mediated Antioxidant Enzyme Induction

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    Haijian Sun

    2017-05-01

    Full Text Available Oxidized low-density lipoprotein (ox-LDL accumulation is one of the critical determinants in endothelial dysfunction in many cardiovascular diseases such as atherosclerosis. C1q/TNF-related protein 9 (CTRP9 is identified to be an adipocytokine with cardioprotective properties. However, the potential roles of CTRP9 in endothelial function remain largely elusive. In the present study, the effects of CTRP9 on the proliferation, apoptosis, migration, angiogenesis, nitric oxide (NO production and oxidative stress in human umbilical vein endothelial cells (HUVECs exposed to ox-LDL were investigated. We observed that treatment with ox-LDL inhibited the proliferation, migration, angiogenesis and the generation of NO, while stimulated the apoptosis and reactive oxygen species (ROS production in HUVECs. Incubation of HUVECs with CTRP9 rescued ox-LDL-induced endothelial injury. CTRP9 treatment reversed ox-LDL-evoked decreases in antioxidant enzymes including heme oxygenase-1 (HO-1, nicotinamide adenine dinucleotide phosphate (NAD(PH dehydrogenase quinone 1, and glutamate-cysteine ligase (GCL, as well as endothelial nitric oxide synthase (eNOS. Furthermore, CTRP9 induced activation of peroxisome proliferator-activated receptor γ co-activator 1α (PGC1-α and phosphorylation of adenosine monophosphate-activated protein kinase (AMPK. Of interest, AMPK inhibition or PGC1-α silencing abolished CTRP9-mediated antioxidant enzymes levels, eNOS expressions, and endothelial protective effects. Collectively, we provided the first evidence that CTRP9 attenuated ox-LDL-induced endothelial injury by antioxidant enzyme inductions dependent on PGC-1α/AMPK activation.

  4. Educational Psychology: The Distinctive Contribution

    Science.gov (United States)

    Cameron, R. J.

    2006-01-01

    This paper, written in the twenty-first anniversary year of the journal "Educational Psychology in Practice", attempts to uncover those distinctive aspects of the discipline and the practice of applied psychology in general and educational psychology in particular. After considering some of the reasons for attempting this task at this point in…

  5. Separating common from distinctive variation

    NARCIS (Netherlands)

    van der Kloet, F.M.; Sebastián-León, P.; Conesa, A.; Smilde, A.K.; Westerhuis, J.A.

    2016-01-01

    BACKGROUND: Joint and individual variation explained (JIVE), distinct and common simultaneous component analysis (DISCO) and O2-PLS, a two-block (X-Y) latent variable regression method with an integral OSC filter can all be used for the integrated analysis of multiple data sets and decompose them in

  6. Anaesthetic tricaine acts preferentially on neural voltage-gated sodium channels and fails to block directly evoked muscle contraction.

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    Seetharamaiah Attili

    Full Text Available Movements in animals arise through concerted action of neurons and skeletal muscle. General anaesthetics prevent movement and cause loss of consciousness by blocking neural function. Anaesthetics of the amino amide-class are thought to act by blockade of voltage-gated sodium channels. In fish, the commonly used anaesthetic tricaine methanesulphonate, also known as 3-aminobenzoic acid ethyl ester, metacaine or MS-222, causes loss of consciousness. However, its role in blocking action potentials in distinct excitable cells is unclear, raising the possibility that tricaine could act as a neuromuscular blocking agent directly causing paralysis. Here we use evoked electrical stimulation to show that tricaine efficiently blocks neural action potentials, but does not prevent directly evoked muscle contraction. Nifedipine-sensitive L-type Cav channels affecting movement are also primarily neural, suggesting that muscle Nav channels are relatively insensitive to tricaine. These findings show that tricaine used at standard concentrations in zebrafish larvae does not paralyse muscle, thereby diminishing concern that a direct action on muscle could mask a lack of general anaesthesia.

  7. An evil face? Verbal evaluative multi-CS conditioning enhances face-evoked mid-latency magnetoencephalographic responses

    Science.gov (United States)

    Junghöfer, Markus; Rehbein, Maimu Alissa; Maitzen, Julius; Schindler, Sebastian

    2017-01-01

    Abstract Humans have a remarkable capacity for rapid affective learning. For instance, using first-order US such as odors or electric shocks, magnetoencephalography (MEG) studies of multi-CS conditioning demonstrate enhanced early (<150 ms) and mid-latency (150–300 ms) visual evoked responses to affectively conditioned faces, together with changes in stimulus evaluation. However, particularly in social contexts, human affective learning is often mediated by language, a class of complex higher-order US. To elucidate mechanisms of this type of learning, we investigate how face processing changes following verbal evaluative multi-CS conditioning. Sixty neutral expression male faces were paired with phrases about aversive crimes (30) or neutral occupations (30). Post conditioning, aversively associated faces evoked stronger magnetic fields in a mid-latency interval between 220 and 320 ms, localized primarily in left visual cortex. Aversively paired faces were also rated as more arousing and more unpleasant, evaluative changes occurring both with and without contingency awareness. However, no early MEG effects were found, implying that verbal evaluative conditioning may require conceptual processing and does not engage rapid, possibly sub-cortical, pathways. Results demonstrate the efficacy of verbal evaluative multi-CS conditioning and indicate both common and distinct neural mechanisms of first- and higher-order multi-CS conditioning, thereby informing theories of associative learning. PMID:28008078

  8. High-throughput analysis of stimulus-evoked behaviors in Drosophila larva reveals multiple modality-specific escape strategies.

    Science.gov (United States)

    Ohyama, Tomoko; Jovanic, Tihana; Denisov, Gennady; Dang, Tam C; Hoffmann, Dominik; Kerr, Rex A; Zlatic, Marta

    2013-01-01

    All organisms react to noxious and mechanical stimuli but we still lack a complete understanding of cellular and molecular mechanisms by which somatosensory information is transformed into appropriate motor outputs. The small number of neurons and excellent genetic tools make Drosophila larva an especially tractable model system in which to address this problem. We developed high throughput assays with which we can simultaneously expose more than 1,000 larvae per man-hour to precisely timed noxious heat, vibration, air current, or optogenetic stimuli. Using this hardware in combination with custom software we characterized larval reactions to somatosensory stimuli in far greater detail than possible previously. Each stimulus evoked a distinctive escape strategy that consisted of multiple actions. The escape strategy was context-dependent. Using our system we confirmed that the nociceptive class IV multidendritic neurons were involved in the reactions to noxious heat. Chordotonal (ch) neurons were necessary for normal modulation of head casting, crawling and hunching, in response to mechanical stimuli. Consistent with this we observed increases in calcium transients in response to vibration in ch neurons. Optogenetic activation of ch neurons was sufficient to evoke head casting and crawling. These studies significantly increase our understanding of the functional roles of larval ch neurons. More generally, our system and the detailed description of wild type reactions to somatosensory stimuli provide a basis for systematic identification of neurons and genes underlying these behaviors.

  9. Effects of some anti-diabetic and cardioprotective agents on proliferation and apoptosis of human coronary artery endothelial cells

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    Eriksson Linnéa

    2012-03-01

    Full Text Available Abstract Background The leading cause of death for patients suffering from diabetes is macrovascular disease. Endothelial dysfunction is often observed in type 2 diabetic patients and it is considered to be an important early event in the pathogenesis of atherogenesis and cardiovascular disease. Many drugs are clinically applied to treat diabetic patients. However, little is known whether these agents directly interfere with endothelial cell proliferation and apoptosis. This study therefore aimed to investigate how anti-diabetic and cardioprotective agents affect human coronary artery endothelial cells (HCAECs. Methods The effect of anti-diabetic and cardioprotective agents on HCAEC viability, proliferation and apoptosis was studied. Viability was assessed using Trypan blue exclusion; proliferation in 5 mM and 11 mM of glucose was analyzed using [3H]thymidine incorporation. Lipoapoptosis of the cells was investigated by determining caspase-3 activity and the subsequent DNA fragmentation after incubation with the free fatty acid palmitate, mimicking diabetic lipotoxicity. Results Our data show that insulin, metformin, BLX-1002, and rosuvastatin improved HCAEC viability and they could also significantly increase cell proliferation in low glucose. The proliferative effect of insulin and BLX-1002 was also evident at 11 mM of glucose. In addition, insulin, metformin, BLX-1002, pioglitazone, and candesartan significantly decreased the caspase-3 activity and the subsequent DNA fragmentation evoked by palmitate, suggesting a protective effect of the drugs against lipoapoptosis. Conclusion Our results suggest that the anti-diabetic and cardioprotective agents mentioned above have direct and beneficial effects on endothelial cell viability, regeneration and apoptosis. This may add yet another valuable property to their therapeutic effect, increasing their clinical utility in type 2 diabetic patients in whom endothelial dysfunction is a prominent feature

  10. Steady-state visual evoked potentials as a research tool in social affective neuroscience.

    Science.gov (United States)

    Wieser, Matthias J; Miskovic, Vladimir; Keil, Andreas

    2016-12-01

    Like many other primates, humans place a high premium on social information transmission and processing. One important aspect of this information concerns the emotional state of other individuals, conveyed by distinct visual cues such as facial expressions, overt actions, or by cues extracted from the situational context. A rich body of theoretical and empirical work has demonstrated that these socioemotional cues are processed by the human visual system in a prioritized fashion, in the service of optimizing social behavior. Furthermore, socioemotional perception is highly dependent on situational contexts and previous experience. Here, we review current issues in this area of research and discuss the utility of the steady-state visual evoked potential (ssVEP) technique for addressing key empirical questions. Methodological advantages and caveats are discussed with particular regard to quantifying time-varying competition among multiple perceptual objects, trial-by-trial analysis of visual cortical activation, functional connectivity, and the control of low-level stimulus features. Studies on facial expression and emotional scene processing are summarized, with an emphasis on viewing faces and other social cues in emotional contexts, or when competing with each other. Further, because the ssVEP technique can be readily accommodated to studying the viewing of complex scenes with multiple elements, it enables researchers to advance theoretical models of socioemotional perception, based on complex, quasinaturalistic viewing situations. © 2016 Society for Psychophysiological Research.

  11. The thermosensitive potassium channel TREK-1 contributes to coolness-evoked responses of Grueneberg ganglion neurons.

    Science.gov (United States)

    Stebe, Sabrina; Schellig, Katharina; Lesage, Florian; Breer, Heinz; Fleischer, Joerg

    2014-01-01

    Neurons of the Grueneberg ganglion (GG) residing in the vestibule of the murine nose are activated by cool ambient temperatures. Activation of thermosensory neurons is usually mediated by thermosensitive ion channels of the transient receptor potential (TRP) family. However, there is no evidence for the expression of thermo-TRPs in the GG, suggesting that GG neurons utilize distinct mechanisms for their responsiveness to cool temperatures. In search for proteins that render GG neurons responsive to coolness, we have investigated whether TREK/TRAAK channels may play a role; in heterologous expression systems, these potassium channels have been previously found to close upon exposure to coolness, leading to a membrane depolarization. The results of the present study indicate that the thermosensitive potassium channel TREK-1 is expressed in those GG neurons that are responsive to cool temperatures. Studies analyzing TREK-deficient mice revealed that coolness-evoked responses of GG neurons were clearly attenuated in these animals compared with wild-type conspecifics. These data suggest that TREK-1 channels significantly contribute to the responsiveness of GG neurons to cool temperatures, further supporting the concept that TREK channels serve as thermoreceptors in sensory cells. Moreover, the present findings provide the first evidence of how thermosensory GG neurons are activated by given temperature stimuli in the absence of thermo-TRPs.

  12. Do Event-Related Evoked Potentials Reflect Apathy Tendency and Motivation?

    Science.gov (United States)

    Takayoshi, Hiroyuki; Onoda, Keiichi; Yamaguchi, Shuhei

    2018-01-01

    Apathy is a mental state of diminished motivation. Although the reward system as the foundation of the motivation in the human brain has been studied extensively with neuroimaging techniques, the electrophysiological correlates of motivation and apathy have not been fully explored. Thus, in 14 healthy volunteers, we examined whether event-related evoked potentials (ERP) obtained during a simple number discrimination task with/without rewards reflected apathy tendency and a reward-dependent tendency, which were assessed separately using the apathy scale and the temperament and character inventory (TCI). Participants were asked to judge the size of a number, and received feedback based on their performance in each trial. The P3 amplitudes related to the feedback stimuli increased only in the reward condition. Furthermore, the P2 amplitudes related to the negative feedback stimuli in the reward condition had a positive correlation with the reward-dependent tendency in TCI, whereas the P3 amplitudes related to the positive feedback stimuli had a negative correlation with the apathy score. Our result suggests that the P2 and P3 ERPs to reward-related feedback stimuli are modulated in a distinctive manner by the motivational reward dependence and apathy tendency, and thus the current paradigm may be useful for investigating the brain activity associated with motivation.

  13. Cognitive bias in rats evoked by ultrasonic vocalizations suggests emotional contagion.

    Science.gov (United States)

    Saito, Yumi; Yuki, Shoko; Seki, Yoshimasa; Kagawa, Hiroko; Okanoya, Kazuo

    2016-11-01

    Emotional contagion occurs when an individual acquires the emotional state of another via social cues, and is an important component of empathy. Empathic responses seen in rodents are often explained by emotional contagion. Rats emit 50kHz ultrasonic vocalizations (USVs) in positive contexts, and emit 22kHz USVs in negative contexts. We tested whether rats show positive or negative emotional contagion after hearing conspecific USVs via a cognitive bias task. We hypothesized that animals in positive emotional states would perceive an ambiguous cue as being good (optimistic bias) whereas animals in negative states would perceive the same cue as being bad (pessimistic bias). Rats were trained to respond differently to two sounds with distinct pitches, each of which signaled either a positive or a negative outcome. An ambiguous cue with a frequency falling between the two stimuli tested whether rats interpreted it as positive or negative. Results showed that rats responded to ambiguous cues as positive when they heard the 50kHz USV (positive vocalizations) and negative when they heard the 22kHz USV (negative vocalizations). This suggests that conspecific USVs can evoke emotional contagion, both for positive and negative emotions, to change the affective states in receivers. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Reduced Ang2 expression in aging endothelial cells

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    Hohensinner, P.J., E-mail: philipp.hohensinner@meduniwien.ac.at [Department of Internal Medicine II, Medical University of Vienna, Vienna (Austria); Ebenbauer, B. [Department of Internal Medicine II, Medical University of Vienna, Vienna (Austria); Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna (Austria); Kaun, C.; Maurer, G. [Department of Internal Medicine II, Medical University of Vienna, Vienna (Austria); Huber, K. [Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna (Austria); 3rd Medical Department, Wilhelminenhospital, Vienna (Austria); Sigmund Freud University, Medical Faculty, Vienna (Austria); Wojta, J. [Department of Internal Medicine II, Medical University of Vienna, Vienna (Austria); Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna (Austria); Core Facilities, Medical University of Vienna, Vienna (Austria)

    2016-06-03

    Aging endothelial cells are characterized by increased cell size, reduced telomere length and increased expression of proinflammatory cytokines. In addition, we describe here that aging reduces the migratory distance of endothelial cells. Furthermore, we observe an increase of the quiescence protein Ang1 and a decrease of the endothelial activation protein Ang2 upon aging. Supplementing Ang2 to aged endothelial cells restored their migratory capacity. We conclude that aging shifts the balance of the Ang1/Ang2 network favouring a quiescent state. Activation of endothelial cells in aging might be necessary to enhance wound healing capacities. -- Highlights: •Endothelial cells display signs of aging before reaching proliferative senescence. •Aging endothelial cells express more angiopoietin 1 and less angiopoietin 2 than young endothelial cells. •Migratory capacity is reduced in aging endothelial cells.

  15. Allogeneic Mesenchymal Stem Cells Restore Endothelial Function in Heart Failure by Stimulating Endothelial Progenitor Cells

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    Courtney Premer

    2015-05-01

    Interpretation: These findings reveal a novel mechanism whereby allogeneic, but not autologous, MSC administration results in the proliferation of functional EPCs and improvement in vascular reactivity, which in turn restores endothelial function towards normal in patients with HF. These findings have significant clinical and biological implications for the use of MSCs in HF and other disorders associated with endothelial dysfunction.

  16. Assessment of visual disability using visual evoked potentials.

    Science.gov (United States)

    Jeon, Jihoon; Oh, Seiyul; Kyung, Sungeun

    2012-08-06

    The purpose of this study is to validate the use of visual evoked potential (VEP) to objectively quantify visual acuity in normal and amblyopic patients, and determine if it is possible to predict visual acuity in disability assessment to register visual pathway lesions. A retrospective chart review was conducted of patients diagnosed with normal vision, unilateral amblyopia, optic neuritis, and visual disability who visited the university medical center for registration from March 2007 to October 2009. The study included 20 normal subjects (20 right eyes: 10 females, 10 males, ages 9-42 years), 18 unilateral amblyopic patients (18 amblyopic eyes, ages 19-36 years), 19 optic neuritis patients (19 eyes: ages 9-71 years), and 10 patients with visual disability having visual pathway lesions. Amplitude and latencies were analyzed and correlations with visual acuity (logMAR) were derived from 20 normal and 18 amblyopic subjects. Correlation of VEP amplitude and visual acuity (logMAR) of 19 optic neuritis patients confirmed relationships between visual acuity and amplitude. We calculated the objective visual acuity (logMAR) of 16 eyes from 10 patients to diagnose the presence or absence of visual disability using relations derived from 20 normal and 18 amblyopic eyes. Linear regression analyses between amplitude of pattern visual evoked potentials and visual acuity (logMAR) of 38 eyes from normal (right eyes) and amblyopic (amblyopic eyes) subjects were significant [y = -0.072x + 1.22, x: VEP amplitude, y: visual acuity (logMAR)]. There were no significant differences between visual acuity prediction values, which substituted amplitude values of 19 eyes with optic neuritis into function. We calculated the objective visual acuity of 16 eyes of 10 patients to diagnose the presence or absence of visual disability using relations of y = -0.072x + 1.22 (-0.072). This resulted in a prediction reference of visual acuity associated with malingering vs. real

  17. The Intraoperative Effect of Methadone on Somatosensory Evoked Potentials.

    Science.gov (United States)

    Higgs, Maureen; Hackworth, Robert J; John, King; Riffenburgh, Robert; Tomlin, Jeffrey; Wamsley, Brian

    2017-04-01

    Evoked potentials (EP), both somatosensory evoked potentials (SSEP) and transcranial motor evoked potentials (TcMEP), are often used during complex spine surgery to monitor the integrity of spinal pathways during operations in or around the spine. Changes in these monitored EP signals (increased latency and decreased amplitude) may result from ischemia, direct surgical injury, changes in blood pressure, hypoxia, changes in CO2 tension, and anesthetic agents. Typically, a clinically significant change for SSEPs is defined as an increase in latency >10% or a decrease of amplitude >50%. A clinically significant change for TcMEPs is much more complex but is also described in terms of large signal loss or decrease. Opioids have been shown to both increase latency and decrease the amplitude of SSEPs, although this change is usually not clinically significant. There has been a renewed interest in methadone for use in spine and other complex surgeries. However, the effect of methadone on intraoperative monitoring of SSEPs and TcMEPs is unknown. We present the first study to directly look at the effects of methadone on SSEP and TcMEP monitoring during complex spine surgery. The goal of this study was to observe the effect of methadone on an unrandomized set of patients. The primary endpoint was methadone's effect on SSEPs, and the secondary endpoint was methadone's effect on TcMEPs. Adult patients undergoing spine surgery requiring intraoperative neuromonitoring were induced with general anesthesia and had a baseline set of SSEPs and TcMEPs recorded. Next, methadone dosed 0.2 mg/kg/lean body weight was given. Repeat SSEPs and TcMEPs were recorded at 5, 10, and 15 minutes, with the timing based on distribution half-life of methadone between 6 and 8 minutes. Postoperatively, adverse events from methadone administration were collected. There was a statistically significant difference found in SSEPs for N20 latency (95% confidence interval [CI], 0.17-0.53; P=0.028), P37 latency

  18. The Princip cult and what it evokes in Hungary

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    Eric Beckett Weaver

    2016-08-01

    Full Text Available The Princip cult and what it evokes in Hungary On the 28th of June, 1914, a consumptive student, Gavrilo Princip, shot and killed prince Franz Ferdinand, the heir to the throne of the Austro-Hungarian Monarchy. The prince’s wife Sofia was also killed by a stray bullet. In the century that has passed since the assassination, the memory of Princip and the cult constructed around him has been distorted beyond recognition. As local and international politics were altered, so changed Princip’s image. The memory of Princip now evokes strong reactions not only in the South Slav lands, but in Hungary as well. In what follows, we will examine possible sources for the strong reactions evoked by Princip’s memory among Hungarians a century after his act.   Kult Principa i co on ewokuje na Węgrzech W dniu 28 czerwca 1914 roku chory na gruźlicę student Gavrilo Princip zastrzelił księcia Franciszka Ferdynanda, następcę tronu monarchii austro-węgierskiej. Od zbłąkanej kuli zginęła także żona księcia, Zofia. W okresie stulecia, które minęło od tego zabójstwa, pamięć o Principie i kult zbudowany wokół niego przeobraziły się diametralnie. Wraz z przemianami polityki lokalnej i międzynarodowej zmieniało się także postrzeganie Principa. Obecnie pamięć o Principie wywołuje silne reakcje nie tylko na ziemiach południowosłowiańskich, ale również na Węgrzech. Autor artykułu docieka, skąd mogą wypływać silne reakcje, jakie pamięć Principa wywołuje u Węgrów sto lat po jego czynie.

  19. SOMATOSENSORY EVOKED POTENTIALS IN DIABETES MELLITUS TYPE - 2

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    Rekha

    2015-10-01

    Full Text Available Diabetes mellitus is the most common metabolic disorder affecting majority of population. It is estimated that over 400 million people throughout the world have diabetes. It has progressed to be a pandemic from an epidemic causing morbidity and mortality in the population. Among the many complications of diabetes, diabetic neuropathies contribute majorly to the morbidity associated with the disease. Axonal conduction is affected by elevated levels of protein kinase c causing neuronal ischemia; decreased ce llular myoinositol affecting sodium potassium ATPase pump leads to decreased nerve conduction; Somatosensory E voked P otentials (SSEPs reflect the activity of somatosensory pathways mediated through the dorsal columns of the spinal cord and the specific so matosensory cortex. Recording of Somatosensory Evoked Potentials in diabetics is done to assess the sensory involvement of spinal cord. Presence of SEPs provides clear evidence for axonal continuity and by using different stimulation sites, the rate of reg eneration can be determined. Both onset and peak latencies of all SEP components are prolonged in patients with diabetes. Present study is done to compare somatosensory evoked potentials in diabetics and normal subjects. MATERIALS AND METHOD S: The present study was undertaken at the Upgraded Department of Physiology, Osmania Medical College, Koti, Hyderabad. The study was conducted on subjects, both male and female in the age group of 45 to 55 years, suffering from type II diabetes excluding other neurologi cal disorders. Non - invasive method of estimation of nerve conduction studies using SFEMG/EP — Electromyography or evoked potential system (Nicolet systems — USA using surface electrodes with automated computerized monitor attached with printer is used. RESUL TS : ANOVA showed statistically significant N9 latency (right & left sides. Latencies of all the components of SSEPs were more significant than amplitudes in Diabetic

  20. Assessment of visual disability using visual evoked potentials

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    Jeon Jihoon

    2012-08-01

    Full Text Available Abstract Background The purpose of this study is to validate the use of visual evoked potential (VEP to objectively quantify visual acuity in normal and amblyopic patients, and determine if it is possible to predict visual acuity in disability assessment to register visual pathway lesions. Methods A retrospective chart review was conducted of patients diagnosed with normal vision, unilateral amblyopia, optic neuritis, and visual disability who visited the university medical center for registration from March 2007 to October 2009. The study included 20 normal subjects (20 right eyes: 10 females, 10 males, ages 9–42 years, 18 unilateral amblyopic patients (18 amblyopic eyes, ages 19–36 years, 19 optic neuritis patients (19 eyes: ages 9–71 years, and 10 patients with visual disability having visual pathway lesions. Amplitude and latencies were analyzed and correlations with visual acuity (logMAR were derived from 20 normal and 18 amblyopic subjects. Correlation of VEP amplitude and visual acuity (logMAR of 19 optic neuritis patients confirmed relationships between visual acuity and amplitude. We calculated the objective visual acuity (logMAR of 16 eyes from 10 patients to diagnose the presence or absence of visual disability using relations derived from 20 normal and 18 amblyopic eyes. Results Linear regression analyses between amplitude of pattern visual evoked potentials and visual acuity (logMAR of 38 eyes from normal (right eyes and amblyopic (amblyopic eyes subjects were significant [y = −0.072x + 1.22, x: VEP amplitude, y: visual acuity (logMAR]. There were no significant differences between visual acuity prediction values, which substituted amplitude values of 19 eyes with optic neuritis into function. We calculated the objective visual acuity of 16 eyes of 10 patients to diagnose the presence or absence of visual disability using relations of y = −0.072x + 1.22 (−0.072. This resulted in a prediction

  1. Protection of Coronary Endothelial Function during Cardiac Surgery: Potential of Targeting Endothelial Ion Channels in Cardioprotection

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    Qin Yang

    2014-01-01

    Full Text Available Vascular endothelium plays a critical role in the control of blood flow by producing vasoactive factors to regulate vascular tone. Ion channels, in particular, K+ channels and Ca2+-permeable channels in endothelial cells, are essential to the production and function of endothelium-derived vasoactive factors. Impairment of coronary endothelial function occurs in open heart surgery that may result in reduction of coronary blood flow and thus in an inadequate myocardial perfusion. Hyperkalemic exposure and concurrent ischemia-reperfusion during cardioplegic intervention compromise NO and EDHF-mediated function and the impairment involves alterations of K+ channels, that is, KATP and KCa, and Ca2+-permeable TRP channels in endothelial cells. Pharmacological modulation of these channels during ischemia-reperfusion and hyperkalemic exposure show promising results on the preservation of NO and EDHF-mediated endothelial function, which suggests the potential of targeting endothelial K+ and TRP channels for myocardial protection during cardiac surgery.

  2. Endothelial toxicity of unusual nucleotide metabolites.

    Science.gov (United States)

    Pelikant-Malecka, Iwona; Sielicka, Alicja; Kaniewska, Ewa; Smolenski, Ryszard T; Slominska, Ewa M

    2015-08-01

    Endothelium plays a pivotal role in the vascular tone regulation, platelet aggregation, regulation of immune response, inflammation and angiogenesis and its dysfunction is an earliest event in the development of cardiovascular disease. All these processes are affected by endothelial dysfunction. Endothelial toxicity induced by metabolites present in blood is a common scenario in pathology. This involves physiological metabolites such as asymmetric dimethylarginine or homocysteine that are normally excreted by kidneys, but accumulate in pathological conditions, adversely affecting function of endothelium. Our group identified new molecule with potential endothelial toxicity: 4-pirydone-3-carboxamide-1-β-d-ribonucleoside (4PYR). This nucleoside is most likely produced by oxidation of nicotinamide containing precursor by aldehyde oxidase. 4PYR easy crosses cell membrane and become phosphorylated inside the cell giving rise to mono-, di- and triphospates (4PYMP, 4PYDP and 4PYTP). There is considerable evidence that 4PYR is toxic in endothelium and other cell types by disrupting cell energetics evident as ATP depletion. Endothelial dysfunction in the in vitro and in vivo experiments is, however, evident only after prolonged exposure to 4PYR while acute cardiovascular effects are minor. 4PYR endothelial toxicity could be particularly important in patients with chronic renal disease where accumulation of 4PYR and its metabolites is particularly prominent. 4PYR metabolism and toxicity could be blocked by application of nucleoside transport inhibitors and we have proven efficiency of such intervention. We believe that blocking metabolism of endothelial nucleoside toxins such as 4PYR could become important strategy for endothelial targeted therapy. Copyright © 2015. Published by Elsevier Urban & Partner Sp. z o.o.

  3. Sterile inflammation of endothelial cell-derived apoptotic bodies is mediated by interleukin-1α.

    Science.gov (United States)

    Berda-Haddad, Yaël; Robert, Stéphane; Salers, Paul; Zekraoui, Leila; Farnarier, Catherine; Dinarello, Charles A; Dignat-George, Françoise; Kaplanski, Gilles

    2011-12-20

    Sterile inflammation resulting from cell death is due to the release of cell contents normally inactive and sequestered within the cell; fragments of cell membranes from dying cells also contribute to sterile inflammation. Endothelial cells undergoing stress-induced apoptosis release membrane microparticles, which become vehicles for proinflammatory signals. Here, we show that stress-activated endothelial cells release two distinct populations of particles: One population consists of membrane microparticles (bodies. Contrary to present concepts, endothelial microparticles do not contain IL-1α and do not induce neutrophilic chemokines in vitro. In contrast, the large apoptotic bodies contain the full-length IL-1α precursor and the processed mature form. In vitro, these apoptotic bodies induce monocyte chemotactic protein-1 and IL-8 chemokine secretion in an IL-1α-dependent but IL-1β-independent fashion. Injection of these apoptotic bodies into the peritoneal cavity of mice induces elevated serum neutrophil-inducing chemokines, which was prevented by cotreatment with the IL-1 receptor antagonist. Consistently, injection of these large apoptotic bodies into the peritoneal cavity induced a neutrophilic infiltration that was prevented by IL-1 blockade. Although apoptosis is ordinarily considered noninflammatory, these data demonstrate that nonphagocytosed endothelial apoptotic bodies are inflammatory, providing a vehicle for IL-1α and, therefore, constitute a unique mechanism for sterile inflammation.

  4. Urea immunoliposome inhibits human vascular endothelial cell proliferation for hemangioma treatment

    Science.gov (United States)

    2013-01-01

    Background Urea injection has been used in hemangioma treatment as sclerotherapy. It shrinks vascular endothelial cells and induces degeneration, necrosis, and fibrosis. However, this treatment still has disadvantages, such as lacking targeting and difficulty in controlling the urea dosage. Thus, we designed a urea immunoliposome to improve the efficiency of treatment. Methods The urea liposome was prepared by reverse phase evaporation. Furthermore, the urea immunoliposome was generated by coupling the urea liposome with a vascular endothelial growth factor receptor (VEGFR) monoclonal antibody using the glutaraldehyde cross-linking method. The influence of the urea immunoliposome on cultured human hemangioma vascular endothelial cells was observed preliminarily. Results Urea immunoliposomes showed typical liposome morphology under a transmission electron microscope, with an encapsulation percentage of 54.4% and a coupling rate of 36.84% for anti-VEGFR. Treatment with the urea immunoliposome significantly inhibited the proliferation of hemangioma vascular endothelial cells (HVECs) in a time- and dose-dependent manner. Conclusions The urea immunoliposome that we developed distinctly and persistently inhibited the proliferation of HVECs and is expected to be used in clinical hemangioma treatment. PMID:24266957

  5. Spontaneous activity forms a foundation for odor-evoked activation maps in the rat olfactory bulb.

    Science.gov (United States)

    Thompson, Garth J; Sanganahalli, Basavaraju G; Baker, Keeley L; Herman, Peter; Shepherd, Gordon M; Verhagen, Justus V; Hyder, Fahmeed

    2018-01-25

    Fluctuations in spontaneous activity have been observed by many neuroimaging techniques, but because these resting-state changes are not evoked by stimuli, it is difficult to determine how they relate to task-evoked activations. We conducted multi-modal neuroimaging scans of the rat olfactory bulb, both with and without odor, to examine interaction between spontaneous and evoked activities. Independent component analysis of spontaneous fluctuations revealed resting-state networks, and odor-evoked changes revealed activation maps. We constructed simulated activation maps using resting-state networks that were highly correlated to evoked activation maps. Simulated activation maps derived by intrinsic optical signal (IOS), which covers the dorsal portion of the glomerular sheet, significantly differentiated one odor's evoked activation map from the other two. To test the hypothesis that spontaneous activity of the entire glomerular sheet is relevant for representing odor-evoked activations, we used functional magnetic resonance imaging (fMRI) to map the entire glomerular sheet. In contrast to the IOS results, the fMRI-derived simulated activation maps significantly differentiated all three odors' evoked activation maps. Importantly, no evoked activation maps could be significantly differentiated using simulated activation maps produced using phase-randomized resting-state networks. Given that some highly organized resting-state networks did not correlate with any odors' evoked activation maps, we posit that these resting-state networks may characterize evoked activation maps associated with odors not studied. These results emphasize that fluctuations in spontaneous activity are relevant for active processing, signifying the relevance of resting-state mapping to functional neuroimaging. Copyright © 2018. Published by Elsevier Inc.

  6. Multimodality evoked potentials in HTLV-I associated myelopathy.

    Science.gov (United States)

    Kakigi, R; Shibasaki, H; Kuroda, Y; Endo, C; Oda, K; Ikeda, A; Hashimoto, K

    1988-08-01

    Multimodality evoked potentials (EPs) consisting of somatosensory EPs (SEPs), visual EPs (VEPs) and brainstem auditory EPs (BAEPs) were studied in 16 cases with HTLV-I associated myelopathy (HAM). Median nerve SEPs were normal in all cases. In posterior tibial nerve SEPs, the potential recorded at the 12th thoracic spinal process was normal in every case but cortical components were significantly prolonged in 10 cases, although five of these showed no sensory impairment. BAEPs were normal in every case whose hearing was intact, but VEPs were abnormal in two cases whose visual acuities were normal. The present results in HAM indicate predominant lesion in the thoracic cord, and might also suggest some subclinical lesion in the visual pathway.

  7. Temporal suppression and augmentation of click-evoked otoacoustic emissions

    DEFF Research Database (Denmark)

    Verhulst, Sarah; Harte, James; Dau, Torsten

    2008-01-01

    This study investigates temporal suppression of click-evoked otoacoustic emissions (CEOAEs), occurring when a suppressor-click is presented close in time to a test-click (e.g. 0-8ms). Various temporal suppression methods for examining temporal changes in cochlear compression were evaluated...... and measured here for seven subjects, both for short- and long-latency CEOAEs. Long-latency CEOAEs (duration >20ms) typically indicate the presence of synchronised spontaneous otoacoustic emissions (SSOAEs). Temporal suppression can only be linked to changes in CEOAE-compression if the suppressor-click affects...... the CEOAE magnitude. Phase changes induced by the suppressor-click were shown to bias suppression in two ways: (i) when a specific asymmetric measurement method was used and (ii) when synchronisation between the CEOAE and the click-stimuli was incomplete. When such biases were eliminated, temporal...

  8. Auditory evoked responses upon awakening from sleep in human subjects.

    Science.gov (United States)

    Ferrara, M; De Gennaro, L; Ferlazzo, F; Curcio, G; Barattucci, M; Bertini, M

    2001-09-14

    The hypothesis that a state of hypoarousal upon awakening should lead to a decrease in amplitude and an increase in latency of the N1-P2 components of the Auditory Evoked Potentials (AEPs) as compared to presleep wakefulness levels, was evaluated after two nocturnal awakenings and after the final morning awakening from a 7.5-h night of sleep. The amplitude of the N1-P2 complex was reduced upon awakening as compared to presleep wakefulness levels, but only following the first nocturnal awakening, scheduled after the first 2 h of sleep. This result is interpreted as indicating a link between slow wave sleep amount, mainly present during the first part of the night, and lowered levels of brain activation upon awakening. The reaction times, recorded concomitantly to AEPs, were more sensitive to the negative effects of sleep inertia.

  9. Auditory evoked field measurement using magneto-impedance sensors

    Energy Technology Data Exchange (ETDEWEB)

    Wang, K., E-mail: o-kabou@echo.nuee.nagoya-u.ac.jp; Tajima, S.; Song, D.; Uchiyama, T. [Graduate School of Engineering, Nagoya University, Nagoya (Japan); Hamada, N.; Cai, C. [Aichi Steel Corporation, Tokai (Japan)

    2015-05-07

    The magnetic field of the human brain is extremely weak, and it is mostly measured and monitored in the magnetoencephalography method using superconducting quantum interference devices. In this study, in order to measure the weak magnetic field of the brain, we constructed a Magneto-Impedance sensor (MI sensor) system that can cancel out the background noise without any magnetic shield. Based on our previous studies of brain wave measurements, we used two MI sensors in this system for monitoring both cerebral hemispheres. In this study, we recorded and compared the auditory evoked field signals of the subject, including the N100 (or N1) and the P300 (or P3) brain waves. The results suggest that the MI sensor can be applied to brain activity measurement.

  10. Mechanisms of modulation of brain microvascular endothelial cells function by thrombin.

    Science.gov (United States)

    Brailoiu, Eugen; Shipsky, Megan M; Yan, Guang; Abood, Mary E; Brailoiu, G Cristina

    2017-02-15

    Brain microvascular endothelial cells are a critical component of the blood-brain barrier. They form a tight monolayer which is essential for maintaining the brain homeostasis. Blood-derived proteases such as thrombin may enter the brain during pathological conditions like trauma, stroke, and inflammation and further disrupts the permeability of the blood-brain barrier, via incompletely characterized mechanisms. We examined the underlying mechanisms evoked by thrombin in rat brain microvascular endothelial cells (RBMVEC). Our results indicate that thrombin, acting on protease-activated receptor 1 (PAR1) increases cytosolic Ca(2+) concentration in RBMVEC via Ca(2+) release from endoplasmic reticulum through inositol 1,4,5-trisphosphate receptors and Ca(2+) influx from extracellular space. Thrombin increases nitric oxide production; the effect is abolished by inhibition of the nitric oxide synthase or by antagonism of PAR1 receptors. In addition, thrombin increases mitochondrial and cytosolic reactive oxygen species production via PAR1-dependent mechanisms. Immunocytochemistry studies indicate that thrombin increases F-actin stress fibers, and disrupts the tight junctions. Thrombin increased the RBMVEC permeability assessed by a fluorescent flux assay. Taken together, our results indicate multiple mechanisms by which thrombin modulates the function of RBMVEC and may contribute to the blood-brain barrier dysfunction. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Facilitation and refractoriness of the electrically evoked compound action potential.

    Science.gov (United States)

    Hey, Matthias; Müller-Deile, Joachim; Hessel, Horst; Killian, Matthijs

    2017-11-01

    In this study we aim to resolve the contributions of facilitation and refractoriness at very short pulse intervals. Measurements of the refractory properties of the electrically evoked compound action potential (ECAP) of the auditory nerve in cochlear implant (CI) users at inter pulse intervals below 300 μs are influenced by facilitation and recovery effects. ECAPs were recorded using masker pulses with a wide range of current levels relative to the probe pulse levels, for three suprathreshold probe levels and pulse intervals from 13 to 200 μs. Evoked potentials were measured for 21 CI patients by using the masked response extraction artifact cancellation procedure. During analysis of the measurements the stimulation current was not used as absolute value, but in relation to the patient's individual ECAP threshold. This enabled a more general approach to describe facilitation as a probe level independent effect. Maximum facilitation was found for all tested inter pulse intervals at masker levels near patient's individual ECAP threshold, independent from probe level. For short inter pulse intervals an increased N1P1 amplitude was measured for subthreshold masker levels down to 120 CL below patient's individual ECAP threshold in contrast to the recreated state. ECAPs recorded with inter pulse intervals up to 200 μs are influenced by facilitation and recovery. Facilitation effects are most pronounced for masker levels at or below ECAP threshold, while recovery effects increase with higher masker levels above ECAP threshold. The local maximum of the ECAP amplitude for masker levels around ECAP threshold can be explained by the mutual influence of maximum facilitation and minimal refractoriness. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  12. Accuracy of measurement in electrically evoked compound action potentials.

    Science.gov (United States)

    Hey, Matthias; Müller-Deile, Joachim

    2015-01-15

    Electrically evoked compound action potentials (ECAP) in cochlear implant (CI) patients are characterized by the amplitude of the N1P1 complex. The measurement of evoked potentials yields a combination of the measured signal with various noise components but for ECAP procedures performed in the clinical routine, only the averaged curve is accessible. To date no detailed analysis of error dimension has been published. The aim of this study was to determine the error of the N1P1 amplitude and to determine the factors that impact the outcome. Measurements were performed on 32 CI patients with either CI24RE (CA) or CI512 implants using the Software Custom Sound EP (Cochlear). N1P1 error approximation of non-averaged raw data consisting of recorded single-sweeps was compared to methods of error approximation based on mean curves. The error approximation of the N1P1 amplitude using averaged data showed comparable results to single-point error estimation. The error of the N1P1 amplitude depends on the number of averaging steps and amplification; in contrast, the error of the N1P1 amplitude is not dependent on the stimulus intensity. Single-point error showed smaller N1P1 error and better coincidence with 1/√(N) function (N is the number of measured sweeps) compared to the known maximum-minimum criterion. Evaluation of N1P1 amplitude should be accompanied by indication of its error. The retrospective approximation of this measurement error from the averaged data available in clinically used software is possible and best done utilizing the D-trace in forward masking artefact reduction mode (no stimulation applied and recording contains only the switch-on-artefact). Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Can Treadmill Perturbations Evoke Stretch Reflexes in the Calf Muscles?

    Directory of Open Access Journals (Sweden)

    Lizeth H Sloot

    Full Text Available Disinhibition of reflexes is a problem amongst spastic patients, for it limits a smooth and efficient execution of motor functions during gait. Treadmill belt accelerations may potentially be used to measure reflexes during walking, i.e. by dorsal flexing the ankle and stretching the calf muscles, while decelerations show the modulation of reflexes during a reduction of sensory feedback. The aim of the current study was to examine if belt accelerations and decelerations of different intensities applied during the stance phase of treadmill walking can evoke reflexes in the gastrocnemius, soleus and tibialis anterior in healthy subjects. Muscle electromyography and joint kinematics were measured in 10 subjects. To determine whether stretch reflexes occurred, we assessed modelled musculo-tendon length and stretch velocity, the amount of muscle activity, as well as the incidence of bursts or depressions in muscle activity with their time delays, and co-contraction between agonist and antagonist muscle. Although the effect on the ankle angle was small with 2.8±1.0°, the perturbations caused clear changes in muscle length and stretch velocity relative to unperturbed walking. Stretched muscles showed an increasing incidence of bursts in muscle activity, which occurred after a reasonable electrophysiological time delay (163-191 ms. Their amplitude was related to the muscle stretch velocity and not related to co-contraction of the antagonist muscle. These effects increased with perturbation intensity. Shortened muscles showed opposite effects, with a depression in muscle activity of the calf muscles. The perturbations only slightly affected the spatio-temporal parameters, indicating that normal walking was retained. Thus, our findings showed that treadmill perturbations can evoke reflexes in the calf muscles and tibialis anterior. This comprehensive study could form the basis for clinical implementation of treadmill perturbations to functionally

  14. Light-evoked S-nitrosylation in the retina

    Science.gov (United States)

    Tooker, Ryan E; Vigh, Jozsef

    2015-01-01

    Nitric oxide (NO) synthesis in the retina is triggered by light stimulation. NO has been shown to modulate visual signal processing at multiple sites in the vertebrate retina, via activation of the most sensitive target of NO signaling, soluble guanylate cyclase. NO can also alter protein structure and function and exert biological effects directly by binding to free thiol groups of cysteine residues in a chemical reaction called S-nitrosylation. However, in the central nervous system, including the retina, this reaction has not been considered to be significant under physiological conditions. Here we provide immunohistochemical evidence for extensive S-nitrosylation that takes place in the goldfish and mouse retinas under physiologically relevant light intensities, in an intensity-dependent manner, with a strikingly similar pattern in both species. Pre-treatment with NEM, which occludes S-nitrosylation, or with TRIM, an inhibitor of neuronal NO synthase, eliminated the light-evoked increase in S-nitrosylated protein immunofluorescence (SNI) in the retinas of both species. Similarly, light did not increase SNI, above basal levels, in retinas of transgenic mice lacking neuronal NO synthase. Qualitative analysis of the light-adapted mouse retina with mass spectrometry revealed more than 300 proteins that were S-nitrosylated upon illumination, many of which are known to participate directly in retinal signal processing. Our data strongly suggest that in the retina, light-evoked NO production leads to extensive S-nitrosylation and that this process is a significant post-translational modification affecting a wide range of proteins under physiological conditions. PMID:25823749

  15. EFFECT OF SMOKING ON TRASIENTLY EVOKED OTOACOUSTIC EMISSION.

    Science.gov (United States)

    Gegenava, Kh; Japaridze, Sh; Sharashenidze, N; Jalabadze, G; Kevanishvili, Z

    2016-01-01

    Evoked otoacoustic emissions, EOAEs, are proved to be sounds aroused in response to external acoustic stimulus by the cochlear outer hair cells. Transiently evoked otoacoustic emissions, TEOAEs, are the most clinically utilized EOAEs. TEOAEs are detectable in 98% of people with normal hearing, regardless of age or sex, while two ears of any individual produce similar TEOAEs waveforms. The objective of the presented study was the comparison of TEOAE magnitudes in cigarette smokers and nonsmokers. The TEOAE occurrence and characteristics in individuals of both samples with audiometrically proved hearing losses and in those without were also specifically examined. 30 smokers and and 30 nonsmokers within the age range of 30-59 years were involved in the present study after informed concent. OAEs were performed to each subject by Madsen Capella's-OAE/middle ear analyzer-GN Otometrics, (Danmark). After OAE testing each subject was performed routine pure-tone audiometry and tympanometry. Obtained results were statistically treated by the student's t-distribution. According to our results 76.6% of smokers and 3.33% of nonsmokers had marked different level decrease in TEOAE amplitude. Audiographic measurments showed altered audiogram in 6.7% of smokers and in 3.33% of nonsmokers. Based on the above mentioned results we suppose that smoking has significant influence on hearing function, especially on cochlear apparatus; At the same time, TOEAE, as a sensitive method can be used for very early detection of hearing loss, even when there are neither any subjective complains nor some changies on audiogram.

  16. Light-evoked S-nitrosylation in the retina.

    Science.gov (United States)

    Tooker, Ryan E; Vigh, Jozsef

    2015-10-01

    Nitric oxide (NO) synthesis in the retina is triggered by light stimulation. NO has been shown to modulate visual signal processing at multiple sites in the vertebrate retina, via activation of the most sensitive target of NO signaling, soluble guanylate cyclase. NO can also alter protein structure and function and exert biological effects directly by binding to free thiol groups of cysteine residues in a chemical reaction called S-nitrosylation. However, in the central nervous system, including the retina, this reaction has not been considered to be significant under physiological conditions. Here we provide immunohistochemical evidence for extensive S-nitrosylation that takes place in the goldfish and mouse retinas under physiologically relevant light intensities, in an intensity-dependent manner, with a strikingly similar pattern in both species. Pretreatment with N-ethylmaleimide (NEM), which occludes S-nitrosylation, or with 1-(2-trifluromethylphenyl)imidazole (TRIM), an inhibitor of neuronal NO synthase, eliminated the light-evoked increase in S-nitrosylated protein immunofluorescence (SNI) in the retinas of both species. Similarly, light did not increase SNI, above basal levels, in retinas of transgenic mice lacking neuronal NO synthase. Qualitative analysis of the light-adapted mouse retina with mass spectrometry revealed more than 300 proteins that were S-nitrosylated upon illumination, many of which are known to participate directly in retinal signal processing. Our data strongly suggest that in the retina light-evoked NO production leads to extensive S-nitrosylation and that this process is a significant posttranslational modification affecting a wide range of proteins under physiological conditions. © 2015 Wiley Periodicals, Inc.

  17. Endothelial gaps and permeability of venules in rat tracheas exposed to inflammatory stimuli.

    Science.gov (United States)

    McDonald, D M

    1994-01-01

    This study determined the number of endothelial gaps in venules of the rat trachea and related these values to the amount of plasma extravasation after an inflammatory stimulus (neurogenic inflammation). From 1 to 30 min after the stimulus, vessels were fixed by vascular perfusion, and endothelial cell borders were stained with silver nitrate, which made it possible to quantify the number and distribution of endothelial gaps. It also was possible to quantify the leukocyte attachment sites, to measure the size, shape, and number of endothelial cells, and to delineate the architecture of the tracheal vasculature. Sites of increased vascular permeability were localized with Monastral blue B, india ink, or fluorescent microspheres. After the stimulus, the silver lines around endothelial cells of postcapillary venules and collecting venules were interrupted by stereotyped silver dots (diam, 1.4 +/- 0.03 microns; +/- SE), which were found by electron microscopy to be silver deposits at endothelial gaps. The dots were most abundant in the smallest postcapillary venules (diam, 7-20 microns) where Monastral blue extravasation was greatest. The number of silver dots (14.4 +/- 0.7 dots/endothelial cell) and the amount of extravasation were maximal 1 min after the stimulus. However, the dots disappeared more slowly (half-life, 3.2 min) than did the extravasation (half-life, 1.3 min). In addition to the silver dots, 64% of the sites at which leukocytes were attached to the endothelium were stained with silver. These sites were marked by silver rings (diam, 3.4 +/- 0.2 microns) and were most numerous in the largest postcapillary venules (diam, 20-40 microns). Most (95%) of the silver rings were located at intercellular junctions but usually were not sites of Monastral blue extravasation. The results indicate that endothelial gaps at intercellular junctions are focal openings, which occupy < 3% of the luminal surface and are distinct from sites of leukocyte attachment. The

  18. Grima: A Distinct Emotion Concept?

    Science.gov (United States)

    Schweiger Gallo, Inge; Fernández-Dols, José-Miguel; Gollwitzer, Peter M.; Keil, Andreas

    2017-01-01

    People experience an unpleasant sensation when hearing a scratch on a board or plate. The present research focuses on this aversive experience known in Spanish as ‘grima’ with no equivalent term in English and German. We hypothesized that this aversive experience constitutes a distinctive, separate emotional concept. In Study 1, we found that the affective meaning of ‘grima’ was closer to disgust than to other emotion concepts. Thus, in Study 2 we explored the features of grima and compared them with disgust. As grima was reported to be predominantly elicited by certain auditory stimuli and associated with a distinctive physiological pattern, Study 3 used direct measures of physiological arousal to test the assumption of a distinctive pattern of physiological responses elicited by auditory stimuli of grima and disgust, and found different effects on heart rate but not on skin conductance. In Study 4, we hypothesized that only participants with an implementation intention geared toward down-regulating grima would be able to successfully weaken the grima- but not disgust- experience. Importantly, this effect was specific as it held true for the grima-eliciting sounds only, but did not affect disgust-related sounds. Finally, Study 5 found that English and German speakers lack a single accessible linguistic label for the pattern of aversive reactions termed by Spanish speaking individuals as ‘grima’, whereas the elicitors of other emotions were accessible and accurately identified by German, English, as well as Spanish speakers. PMID:28217102

  19. Interleukin-1 exerts distinct actions on different cell types of the brain in vitro

    Directory of Open Access Journals (Sweden)

    Ying An

    2011-01-01

    Full Text Available Ying An, Qun Chen, Ning QuanDepartment of Oral Biology, Ohio State University, Columbus, OH, USAAbstract: Interleukin-1 (IL-1 is a critical neuroinflammatory mediator in the central nervous system (CNS. In this study, we investigated the effect of IL-1 on inducing inflammation-related gene expression in three astrocyte, two microglial, and one brain endothelial cell line. Interleukin-1 beta (IL-1β is found to be produced by the two microglial cell lines constitutively, but these cells do not respond to IL-1β stimulation. The three astrocyte cell lines responded to IL-1ß stimulation by expressing MCP-1, CXCL-1, and VCAM-1, but different subtypes of astrocytes exhibited different expression profiles after IL-1β stimulation. The brain endothelial cells showed strongest response to IL-1β by producing MCP-1, CXCL-1, VCAM-1, ICAM-1, IL-6, and COX-2 mRNA. The induction of endothelial COX-2 mRNA is shown to be mediated by p38 MAPK pathway, whereas the induction of other genes is mediated by the NF-κB pathway. These results demonstrate that IL-1 exerts distinct cell type-specific action in CNS cells and suggest that IL-1-mediated neuroinflammation is the result of the summation of multiple responses from different cell types in the CNS to IL-1.Keywords: astrocyte, microglia, endothelial cells, signal transduction pathways, gene expression 

  20. Investigating the roles of odor-evoked oscillations in information processing in the turtle olfactory bulb

    Science.gov (United States)

    Kim, Soyoun

    It has been earlier established that presentation of an odorant stimulus to the turtle evokes specific spatio-temporal responses in the olfactory bulb. This response includes three distinct oscillatory patterns (rostral, middle and caudal) that have different spatial (locations and scopes) and temporal (frequencies and delay from the odorant onset) properties. In this thesis we investigate, using modeling and experimental approaches; the mechanisms of formation and the role of the oscillatory patterning in the turtle olfactory bulb. We have built a computational model that incorporates the basic anatomy and neurophysiology of the olfactory bulb to investigate how the observed patterns relate to activity of individual neurons and what roles they could play in olfactory information processing. We show that three basic anatomical/physiological properties of the olfactory network underlie formation of a temporal sequence of simultaneous activations of glomerular modules: fast synaptic inhibition between populations of excitatory and inhibitory cells, slow self-inhibition observed on excitatory cells; and input strength. The model suggests that the role of oscillations is to organize the neural activity in a temporal sequence which groups the activation of glomerular modules based on the input strength similarity. We show that this type of code explains particularly well the experimental findings reported also by other groups, showing that temporal patterning may mediate discrimination of similar odorants. Furthermore, we showed that within our model, feedback from cortical regions of the brain could modulate oscillatory patterning and provide mechanisms to generate experimentally observed period doubling in one of the oscillations. This requires the cortical processing to act as a type of coincidence modulator and provide functional coupling between excitatory modules that is absent in the bulbar network. This hypothesis is partially supported by our experiments that

  1. Endothelial monolayer permeability under controlled oxygen tension.

    Science.gov (United States)

    Funamoto, Kenichi; Yoshino, Daisuke; Matsubara, Kento; Zervantonakis, Ioannis K; Funamoto, Kiyoe; Nakayama, Masafumi; Masamune, Jun; Kimura, Yoshitaka; Kamm, Roger D

    2017-06-19

    Endothelial permeability has been extensively investigated in the context of pathologies such as cancer and also in studies of drug delivery from the circulation. Hypoxia is a critical regulator of endothelial cell (EC) behavior and affects the barrier function of endothelial linings, yet its role has been little studied. This paper reveals the effect of hypoxia on the permeability of an EC monolayer by cellular experiments using a microfluidic device and a conventional cell culture dish. Human umbilical vein endothelial cells (HUVECs) were seeded into one microfluidic channel, creating an EC monolayer on each vertical surface of a collagen gel confined to a central chamber. Oxygen tension was regulated to produce normoxic (21% O2) or hypoxic (3% O2) conditions by the supply of gas mixtures of oxygen, carbon dioxide, and nitrogen at predefined ratios into channels fabricated into the device. Permeability of the EC monolayer quantified by analyzing diffusion of fluorescence-labelled dextrans into the collagen gel increases with barrier function loss by 6 hour hypoxic exposure, showing 11-fold and 4-fold increases for 70 kDa and 10 kDa dextrans, respectively, on average. Consistent with this, subsequent immunofluorescent staining and separate western blot analysis of HUVECs on a culture dish demonstrate loose cell-cell adhesion resulting from internalization of VE-cadherin under hypoxia. Thus, hypoxic stress increases endothelial permeability by altering cell-cell junction integrity.

  2. Dietary phosphorus acutely impairs endothelial function.

    Science.gov (United States)

    Shuto, Emi; Taketani, Yutaka; Tanaka, Rieko; Harada, Nagakatsu; Isshiki, Masashi; Sato, Minako; Nashiki, Kunitaka; Amo, Kikuko; Yamamoto, Hironori; Higashi, Yukihito; Nakaya, Yutaka; Takeda, Eiji

    2009-07-01

    Excessive dietary phosphorus may increase cardiovascular risk in healthy individuals as well as in patients with chronic kidney disease, but the mechanisms underlying this risk are not completely understood. To determine whether postprandial hyperphosphatemia may promote endothelial dysfunction, we investigated the acute effect of phosphorus loading on endothelial function in vitro and in vivo. Exposing bovine aortic endothelial cells to a phosphorus load increased production of reactive oxygen species, which depended on phosphorus influx via sodium-dependent phosphate transporters, and decreased nitric oxide production via inhibitory phosphorylation of endothelial nitric oxide synthase. Phosphorus loading inhibited endothelium-dependent vasodilation of rat aortic rings. In 11 healthy men, we alternately served meals containing 400 mg or 1200 mg of phosphorus in a double-blind crossover study and measured flow-mediated dilation of the brachial artery before and 2 h after the meals. The high dietary phosphorus load increased serum phosphorus at 2 h and significantly decreased flow-mediated dilation. Flow-mediated dilation correlated inversely with serum phosphorus. Taken together, these findings suggest that endothelial dysfunction mediated by acute postprandial hyperphosphatemia may contribute to the relationship between serum phosphorus level and the risk for cardiovascular morbidity and mortality.

  3. [Assessment of endothelial function in autoimmune diseases].

    Science.gov (United States)

    Benhamou, Y; Bellien, J; Armengol, G; Gomez, E; Richard, V; Lévesque, H; Joannidès, R

    2014-08-01

    Numerous autoimmune-inflammatory rheumatic diseases have been associated with accelerated atherosclerosis or other types of vasculopathy leading to an increase in cardiovascular disease incidence. In addition to traditional cardiovascular risk factors, endothelial dysfunction is an important early event in the pathogenesis of atherosclerosis, contributing to plaque initiation and progression. Endothelial dysfunction is characterized by a shift of the actions of the endothelium toward reduced vasodilation, a proinflammatory and a proadhesive state, and prothrombic properties. Therefore, assessment of endothelial dysfunction targets this vascular phenotype using several biological markers as indicators of endothelial dysfunction. Measurements of soluble adhesion molecules (ICAM-1, VCAM-1, E-selectin), pro-thrombotic factors (thrombomodulin, von Willebrand factor, plasminogen activator inhibitor-1) and inflammatory cytokines are most often performed. Regarding the functional assessment of the endothelium, the flow-mediated dilatation of conduit arteries is a non-invasive method widely used in pathophysiological and interventional studies. In this review, we will briefly review the most relevant information upon endothelial dysfunction mechanisms and explorations. We will summarize the similarities and differences in the biological and functional assessments of the endothelium in different autoimmune diseases. Copyright © 2013 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  4. Endothelial Extracellular Vesicles-Promises and Challenges.

    Science.gov (United States)

    Hromada, Carina; Mühleder, Severin; Grillari, Johannes; Redl, Heinz; Holnthoner, Wolfgang

    2017-01-01

    Extracellular vesicles, including exosomes, microparticles, and apoptotic bodies, are phospholipid bilayer-enclosed vesicles that have once been considered as cell debris lacking biological functions. However, they have recently gained immense interest in the scientific community due to their role in intercellular communication, immunity, tissue regeneration as well as in the onset, and progression of various pathologic conditions. Extracellular vesicles of endothelial origin have been found to play a versatile role in the human body, since they are on the one hand known to contribute to cardiovascular diseases, but on the other hand have also been reported to promote endothelial cell survival. Hence, endothelial extracellular vesicles hold promising therapeutic potential to be used as a new tool to detect as well as treat a great number of diseases. This calls for clinically approved, standardized, and efficient isolation and characterization protocols to harvest and purify endothelial extracellular vesicles. However, such methods and techniques to fulfill stringent requirements for clinical trials have yet to be developed or are not harmonized internationally. In this review, recent advances and challenges in the field of endothelial extracellular vesicle research are discussed and current problems and limitations regarding isolation and characterization are pointed out.

  5. Differential Gene Expression of Primary Cultured Lymphatic and Blood Vascular Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Gregory M. Nelson

    2007-12-01

    Full Text Available Blood vascular endothelial cells (BECs and the developmentally related lymphatic endothelial cells (LECs create complementary, yet distinct vascular networks. Each endothelial cell type interacts with flowing fluid and circulating cells, yet each vascular system has evolved specialized gene expression programs and thus both cell types display different phenotypes. BECs and LECs express distinct genes that are unique to their specific vascular microenvironment. Tumors also take advantage of the molecules that are expressed in these vascular systems to enhance their metastatic potential. We completed transcriptome analyses on primary cultured LECs and BECs, where each comparative set was isolated from the same individual. Differences were resolved in the expression of several major categories, such as cell adhesion molecules (CAMs, cytokines, cytokine receptors. We have identified new molecules that are associated with BECs (e.g., claudin-9, CXCL11, neurexin-1, neurexin-2, the neuronal growth factor regulator-1 and LECs (e.g., claudin-7, CD58, hyaluronan and proteoglycan link protein 1 (HAPLN1, the poliovirus receptor-related 3 molecule that may lead to novel therapeutic treatments for diseases of lymphatic or blood vessels, including metastasis of cancer to lymph nodes or distant organs.

  6. How Do RIM-BPs Link Voltage-Gated Ca(2+) Channels to Evoked Neurotransmitter Release?

    Science.gov (United States)

    Li, Ying C; Kavalali, Ege T

    2015-09-23

    Coupling between voltage-gated Ca(2+) influx and synaptic vesicle exocytosis is essential for rapid evoked neurotransmission. Acuna et al. show that the knockout of RIM-BPs, which are key structural components of this coupling, decreases the reliability of evoked neurotransmitter release. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Sex and Ear Differences in Spontaneous and Click-Evoked Otoacoustic Emissions in Young Adults

    Science.gov (United States)

    Snihur, Adrian W. K.; Hampson, Elizabeth

    2011-01-01

    Effects of sex and handedness on the production of spontaneous and click-evoked otoacoustic emissions (OAEs) were explored in a non-hearing impaired population (ages 17-25 years). A sex difference in OAEs, either produced spontaneously (spontaneous OAEs or SOAEs) or in response to auditory stimuli (click-evoked OAEs or CEOAEs) has been reported in…

  8. The Nature and Process of Development in Averaged Visually Evoked Potentials: Discussion on Pattern Structure.

    Science.gov (United States)

    Izawa, Shuji; Mizutani, Tohru

    This paper examines the development of visually evoked EEG patterns in retarded and normal subjects. The paper focuses on the averaged visually evoked potentials (AVEP) in the central and occipital regions of the brain in eyes closed and eyes open conditions. Wave pattern, amplitude, and latency are examined. The first section of the paper reviews…

  9. One Year of Musical Training Affects Development of Auditory Cortical-Evoked Fields in Young Children

    Science.gov (United States)

    Fujioka, Takako; Ross, Bernhard; Kakigi, Ryusuke; Pantev, Christo; Trainor, Laurel J.

    2006-01-01

    Auditory evoked responses to a violin tone and a noise-burst stimulus were recorded from 4- to 6-year-old children in four repeated measurements over a 1-year period using magnetoencephalography (MEG). Half of the subjects participated in musical lessons throughout the year; the other half had no music lessons. Auditory evoked magnetic fields…

  10. Long-term visuo-gustatory appetitive and aversive conditioning potentiate human visual evoked potentials

    DEFF Research Database (Denmark)

    Christoffersen, Gert R.J.; Laugesen, Jakob L.; Møller, Per

    2017-01-01

    and aversive visuo-gustatory conditioning were studied with high density EEG-recordings focusing on late components in the visual evoked potentials (VEPs), specifically the N2-P3 waves. Unfamiliar images were paired with either a pleasant or an unpleasant juice and VEPs evoked by the images were compared...

  11. The effect of changes in perilymphatic K+ on the vestibular evoked potential in the guinea pig

    NARCIS (Netherlands)

    Kingma, C. M.; Wit, H. P.

    2010-01-01

    To investigate the effect on the functioning of the vestibular system of a rupture of Reissner's membrane, artificial endolymph was injected in scala media of ten guinea pigs and vestibular evoked potentials (VsEPs), evoked by vertical acceleration pulses, were measured. Directly after injection of

  12. Gender differences in rival characteristics that evoke jealousy in response to emotional versus sexual infidelity

    NARCIS (Netherlands)

    Buunk, Abraham (Bram); Dijkstra, Pieternel

    2004-01-01

    Previous research has shown that in men jealousy is evoked more by a rival's status-related characteristics than in women, whereas in women jealousy is evoked more by a rival's physical attractiveness than in men. The present study examined whether the occurrence of this gender difference depends

  13. Long-Term Visuo-Gustatory Appetitive and Aversive Conditioning Potentiate Human Visual Evoked Potentials

    DEFF Research Database (Denmark)

    Christoffersen, Gert Rene Juul; Laugesen, Jakob Lund; Møller, Per

    2017-01-01

    and aversive visuo-gustatory conditioning were studied with high density EEG-recordings focusing on late components in the visual evoked potentials (VEPs), specifically the N2-P3 waves. Unfamiliar images were paired with either a pleasant or an unpleasant juice and VEPs evoked by the images were compared...

  14. Endothelial progenitor cells in chronic obstructive pulmonary disease and emphysema

    Science.gov (United States)

    Tracy, Russell P.; Parikh, Megha A.; Hoffman, Eric A.; Shimbo, Daichi; Austin, John H. M.; Smith, Benjamin M.; Hueper, Katja; Vogel-Claussen, Jens; Lima, Joao; Gomes, Antoinette; Watson, Karol; Kawut, Steven; Barr, R. Graham

    2017-01-01

    Endothelial injury is implicated in the pathogenesis of COPD and emphysema; however the role of endothelial progenitor cells (EPCs), a marker of endothelial cell repair, and circulating endothelial cells (CECs), a marker of endothelial cell injury, in COPD and its subphenotypes is unresolved. We hypothesized that endothelial progenitor cell populations would be decreased in COPD and emphysema and that circulating endothelial cells would be increased. Associations with other subphenotypes were examined. The Multi-Ethnic Study of Atherosclerosis COPD Study recruited smokers with COPD and controls age 50–79 years without clinical cardiovascular disease. Endothelial progenitor cell populations (CD34+KDR+ and CD34+KDR+CD133+ cells) and circulating endothelial cells (CD45dimCD31+CD146+CD133-) were measured by flow cytometry. COPD was defined by standard spirometric criteria. Emphysema was assessed qualitatively and quantitatively on CT. Full pulmonary function testing and expiratory CTs were measured in a subset. Among 257 participants, both endothelial progenitor cell populations, and particularly CD34+KDR+ endothelial progenitor cells, were reduced in COPD. The CD34+KDR+CD133+ endothelial progenitor cells were associated inversely with emphysema extent. Both endothelial progenitor cell populations were associated inversely with extent of panlobular emphysema and positively with diffusing capacity. Circulating endothelial cells were not significantly altered in COPD but were inversely associated with pulmonary microvascular blood flow on MRI. There was no consistent association of endothelial progenitor cells or circulating endothelial cells with measures of gas trapping. These data provide evidence that endothelial repair is impaired in COPD and suggest that this pathological process is specific to emphysema. PMID:28291826

  15. Endothelial progenitor cells in chronic obstructive pulmonary disease and emphysema.

    Science.gov (United States)

    Doyle, Margaret F; Tracy, Russell P; Parikh, Megha A; Hoffman, Eric A; Shimbo, Daichi; Austin, John H M; Smith, Benjamin M; Hueper, Katja; Vogel-Claussen, Jens; Lima, Joao; Gomes, Antoinette; Watson, Karol; Kawut, Steven; Barr, R Graham

    2017-01-01

    Endothelial injury is implicated in the pathogenesis of COPD and emphysema; however the role of endothelial progenitor cells (EPCs), a marker of endothelial cell repair, and circulating endothelial cells (CECs), a marker of endothelial cell injury, in COPD and its subphenotypes is unresolved. We hypothesized that endothelial progenitor cell populations would be decreased in COPD and emphysema and that circulating endothelial cells would be increased. Associations with other subphenotypes were examined. The Multi-Ethnic Study of Atherosclerosis COPD Study recruited smokers with COPD and controls age 50-79 years without clinical cardiovascular disease. Endothelial progenitor cell populations (CD34+KDR+ and CD34+KDR+CD133+ cells) and circulating endothelial cells (CD45dimCD31+CD146+CD133-) were measured by flow cytometry. COPD was defined by standard spirometric criteria. Emphysema was assessed qualitatively and quantitatively on CT. Full pulmonary function testing and expiratory CTs were measured in a subset. Among 257 participants, both endothelial progenitor cell populations, and particularly CD34+KDR+ endothelial progenitor cells, were reduced in COPD. The CD34+KDR+CD133+ endothelial progenitor cells were associated inversely with emphysema extent. Both endothelial progenitor cell populations were associated inversely with extent of panlobular emphysema and positively with diffusing capacity. Circulating endothelial cells were not significantly altered in COPD but were inversely associated with pulmonary microvascular blood flow on MRI. There was no consistent association of endothelial progenitor cells or circulating endothelial cells with measures of gas trapping. These data provide evidence that endothelial repair is impaired in COPD and suggest that this pathological process is specific to emphysema.

  16. The cytotoxicity evaluation of magnetic iron oxide nanoparticles on human aortic endothelial cells.

    Science.gov (United States)

    Ge, Gaoyuan; Wu, Hengfang; Xiong, Fei; Zhang, Yu; Guo, Zhirui; Bian, Zhiping; Xu, Jindan; Gu, Chunrong; Gu, Ning; Chen, Xiangjian; Yang, Di

    2013-05-07

    One major obstacle for successful application of nanoparticles in medicine is its potential nanotoxicity on the environment and human health. In this study, we evaluated the cytotoxicity effect of dimercaptosuccinic acid-coated iron oxide (DMSA-Fe2O3) using cultured human aortic endothelial cells (HAECs). Our results showed that DMSA-Fe2O3 in the culture medium could be absorbed into HAECs, and dispersed in the cytoplasm. The cytotoxicity effect of DMSA-Fe2O3 on HAECs was dose-dependent, and the concentrations no more than 0.02 mg/ml had little toxic effect which were revealed by tetrazolium dye assay. Meanwhile, the cell injury biomarker, lactate dehydrogenase, was not significantly higher than that from control cells (without DMSA-Fe2O3). However, the endocrine function for endothelin-1 and prostacyclin I-2, as well as the urea transporter function, was altered even without obvious evidence of cell injury in this context. We also showed by real-time PCR analysis that DMSA-Fe2O3 exposure resulted in differential effects on the expressions of pro- and anti-apoptosis genes of HAECs. Meanwhile, it was noted that DMSA-Fe2O3 exposure could activate the expression of genes related to oxidative stress and adhesion molecules, which suggested that inflammatory response might be evoked. Moreover, we demonstrated by in vitro endothelial tube formation that even a small amount of DMSA-Fe2O3 (0.01 and 0.02 mg/ml) could inhibit angiogenesis by the HAECs. Altogether, these results indicate that DMSA-Fe2O3 have some cytotoxicity that may cause side effects on normal endothelial cells.

  17. Prevention of endothelial dysfunction in streptozotocin-induced diabetic rats by gliclazide treatment.

    Science.gov (United States)

    Vallejo, S; Angulo, J; Peiró, C; Sánchez-Ferrer, A; Cercas, E; Llergo, J L; Nevado, J; Sánchez-Ferrer, C F; Rodríguez-Mañas, L

    2000-01-01

    The aim of the present work was to analyze whether the oral hypoglycemic drug gliclazide affects diabetic endothelial dysfunction in streptozotocin-induced diabetic rats. Gliclazide was compared with glibenclamide, ascorbic acid, and aminoguanidine. An insulin-dependent model of diabetes was selected to exclude insulin-releasing effects of the drugs. Both in isolated aortic segments and mesenteric microvessels, endothelium-dependent relaxation evoked by acetylcholine (ACh, 1 nM to 10 microM) was significantly reduced in vessels from diabetic animals. This impairment was reversed when the segments were previously incubated with 100 U/ml superoxide dismutase. When streptozotocin-induced diabetic rats were orally treated from the time of diabetes induction with gliclazide (10 mg/kg) or ascorbic acid (250 mg/kg), ACh-induced endothelium-dependent relaxation was well preserved both in aortic segments and mesenteric microvessels. In addition, the impaired vasodilatation to exogenous nitric oxide (NO) in aortic segments was also improved in gliclazide-treated diabetic rats. On the other hand, oral treatment with glibenclamide (1 and 10 mg/kg) or aminoguanidine (250 mg/kg) did not produce significant improvements in diabetic endothelial dysfunction. We conclude that gliclazide reverses the endothelial dysfunction associated with diabetes. This effect appears to be due not to the metabolic actions of the drug but rather to its antioxidant properties, as it can be mimicked by other antioxidants. We propose that the mechanism involved is the inactivation of reactive oxygen species, which are increased in diabetes probably as a result of increased early protein glycosylation products, such as glycosylated hemoglobin (HbA(1c)). These effects of gliclazide are not shared by other oral hypoglycemic agent such as glibenclamide, or by blockade of advanced glycosylation end product (AGE) generation with aminoguanidine.

  18. The involuntary nature of music-evoked autobiographical memories in Alzheimer's disease.

    Science.gov (United States)

    El Haj, Mohamad; Fasotti, Luciano; Allain, Philippe

    2012-03-01

    The main objective of this paper was to examine the involuntary nature of music-evoked autobiographical memories. For this purpose, young adults, older adults, and patients with a clinical diagnosis of probable Alzheimer's disease (AD) were asked to remember autobiographical events in two conditions: after being exposed to their own chosen music, and in silence. Compared to memories evoked in silence, memories evoked in the "Music" condition were found to be more specific, accompanied by more emotional content and impact on mood, and retrieved faster. In addition, these memories engaged less executive processes. Thus, with all these characteristics and the fact that they are activated by a perceptual cue (i.e., music), music-evoked autobiographic memories have all the features to be considered as involuntary memories. Our paper reveals several characteristics of music-evoked autobiographical memories in AD patients and offers a theoretical background for this phenomenon. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Dorsal root activity evoked by stimulation of vagina-cervix-uterus junction in the rat.

    Science.gov (United States)

    Tovar, Anibal; Lara-Garcia, Miguel; Cruz, Yolanda; Pacheco, Pablo

    2013-02-16

    In the present study, we characterized the evoked electrical activity from T(13) to S(2) dorsal roots (DRs) during glass probe-stimulation of the vagina-cervix-uterus junction (VCUJ) of female Wistar rats. The results showed that gentle stimulation of VCUJ evoked high-amplitude electrical activity in L(3) and L(6) DRs. Hypogastric or pelvic nerve transection failed to abolish this activity. L(6)-S(1) spinal trunk transection abolished the high-amplitude electrical activity evoked in L(6) DR, while transection of the lumbosacral trunk blocked the high-amplitude electrical activity evoked in L(3) DR. These data suggest that during copulation, penile intromission likely activates the low-threshold sensory receptors of the VCUJ, thereby evoking sensory neural activity that enters the spinal cord via L(3) and L(6) dorsal roots, whose axons travel through the lumbosacral trunk and pudendal nerve. Copyright © 2013. Published by Elsevier B.V.

  20. Endothelial nitric oxide synthase uncoupling: a novel pathway in OSA induced vascular endothelial dysfunction.

    Science.gov (United States)

    Varadharaj, Saradhadevi; Porter, Kyle; Pleister, Adam; Wannemacher, Jacob; Sow, Angela; Jarjoura, David; Zweier, Jay L; Khayat, Rami N

    2015-02-01

    The mechanism of vascular endothelial dysfunction (VED) and cardiovascular disease in obstructive sleep apnea (OSA) is unknown. We performed a comprehensive evaluation of endothelial nitric oxide synthase (eNOS) function directly in the microcirculatory endothelial tissue of OSA patients who have very low cardiovascular risk status. Nineteen OSA patients underwent gluteal biopsies before, and after effective treatment of OSA. We measured superoxide (O2(•-)) and nitric oxide (NO) in the microcirculatory endothelium using confocal microscopy. We evaluated the effect of the NOS inhibitor l-Nitroarginine-Methyl-Ester (l-NAME) and the NOS cofactor tetrahydrobiopterin (BH4) on endothelial O2(•-) and NO in patient endothelial tissue before and after treatment. We found that eNOS is dysfunctional in OSA patients pre-treatment, and is a source of endothelial O2(•-) overproduction. eNOS dysfunction was reversible with the addition of BH4. These findings provide a new mechanism of endothelial dysfunction in OSA patients and a potentially targetable pathway for treatment of cardiovascular risk in OSA. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Pre-Descemet's endothelial keratoplasty (PDEK).

    Science.gov (United States)

    Agarwal, Amar; Dua, Harminder S; Narang, Priya; Kumar, Dhivya A; Agarwal, Ashvin; Jacob, Soosan; Agarwal, Athiya; Gupta, Ankur

    2014-09-01

    A new surgical technique for endothelial keratoplasty is described, in which the composite of pre-Descemet's layer (Dua's layer) with Descemet's membrane and endothelium is transplanted subsequent to the removal of the recipient's Descemet's membrane. The technique was performed in five eyes of five patients, with successful attachment of the graft and good postoperative visual recovery in all cases. Postoperative optical coherence tomography showed good graft attachment without interface abnormalities and a mean graft thickness was 28±5.6 μm. This study demonstrates the practicality of the technique, termed pre-Descemet's endothelial keratoplasty (PDEK), which can be a viable option in endothelial keratoplasty with some potential advantages. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  2. Development of Cell Analysis Software for Cultivated Corneal Endothelial Cells.

    Science.gov (United States)

    Okumura, Naoki; Ishida, Naoya; Kakutani, Kazuya; Hongo, Akane; Hiwa, Satoru; Hiroyasu, Tomoyuki; Koizumi, Noriko

    2017-11-01

    To develop analysis software for cultured human corneal endothelial cells (HCECs). Software was designed to recognize cell borders and to provide parameters such as cell density, coefficient of variation, and polygonality of cultured HCECs based on phase contrast images. Cultured HCECs with high or low cell density were incubated with Ca-free and Mg-free phosphate-buffered saline for 10 minutes to reveal the cell borders and were then analyzed with software (n = 50). Phase contrast images showed that cell borders were not distinctly outlined, but these borders became more distinctly outlined after phosphate-buffered saline treatment and were recognized by cell analysis software. The cell density value provided by software was similar to that obtained using manual cell counting by an experienced researcher. Morphometric parameters, such as the coefficient of variation and polygonality, were also produced by software, and these values were significantly correlated with cell density (Pearson correlation coefficients -0.62 and 0.63, respectively). The software described here provides morphometric information from phase contrast images, and it enables subjective and noninvasive quality assessment for tissue engineering therapy of the corneal endothelium.

  3. Adenovirus vectors can induce activation of endothelial cells: CD40 ...

    African Journals Online (AJOL)

    Adenovirus vectors can induce activation of endothelial cells: CD40-CD40L interactions partly participate in the endothelial cells activation induced by adenovirus vectors in an NF-kappaB-dependent manner.

  4. Identification of epigenetically silenced genes in tumor endothelial cells

    NARCIS (Netherlands)

    Hellebrekers, Debby M. E. I.; Melotte, Veerle; Vire, Emmanuelle; Langenkamp, Elise; Molema, Grietje; Fuks, Francois; Herman, James G.; Van Criekinge, Wim; Griffioen, Arjan W.; van Engeland, Manon

    2007-01-01

    Tumor angiogenesis requires intricate regulation of gene expression in endothelial cells. We recently showed that DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitors directly repress endothelial cell growth and tumor angiogenesis, suggesting that epigenetic modifications mediated

  5. VEGF and endothelial guidance in angiogenic sprouting.

    Science.gov (United States)

    Gerhardt, Holger

    2008-10-01

    The cellular actions of VEGF need to be coordinated to guide vascular patterning during sprouting angiogenesis. Individual endothelial tip cells lead and guide the blood vessel sprout, while neighbouring stalk cells proliferate and form the vascular lumen. Recent studies illustrate how endothelial DLL4/NOTCH signalling, stimulated by VEGF, regulates the sprouting response by limiting tip cell formation in the stalk. The spatial distribution of VEGF, in turn, regulates the shape of the ensuing sprout by directing tip cell migration and determining stalk cell proliferation.

  6. Transcellular migration of neutrophils is a quantitatively significant pathway across dermal microvascular endothelial cells.

    Science.gov (United States)

    Marmon, Shana; Cammer, Michael; Raine, Cedric S; Lisanti, Michael P

    2009-01-01

    Neutrophil extravasation is central to inflammatory skin diseases like psoriasis and atopic dermatitis. In vivo, neutrophils have been shown to migrate through cell-to-cell junctions (paracellular pathway) or directly through the body of the endothelial cell (transcellular pathway). In vitro, however, neutrophil migration is a largely paracellular process where cells preferentially cross at tricellular corners devoid of tight junctions. To approximate the type of cells encountered by extravasating neutrophils in vivo, we developed a neutrophil-migration assay using primary human dermal microvascular endothelial cells. We show here that a large proportion of migrating neutrophils traverse a monolayer of microvascular endothelium using a purely transcellular pathway. In addition, we demonstrate that F-actin is rearranged similarly in neutrophils undergoing diapedesis along either route. This in vitro model closely simulates the physiological process of neutrophil extravasation in vivo and can be further utilized to evaluate the relative contribution of distinct migratory pathways to the pathophysiology of inflammatory skin disease.

  7. Endothelial marker-expressing stromal cells are critical for kidney formation.

    Science.gov (United States)

    Mukherjee, Elina; Maringer, Katherine; Papke, Emily; Bushnell, Daniel; Schaefer, Caitlin; Kramann, Rafael; Ho, Jacqueline; Humphreys, Benjamin D; Bates, Carlton; Sims-Lucas, Sunder

    2017-09-01

    Kidneys are highly vascularized and contain many distinct vascular beds. However, the origins of renal endothelial cells and roles of the developing endothelia in the formation of the kidney are unclear. We have shown that the Foxd1-positive renal stroma gives rise to endothelial marker-expressing progenitors that are incorporated within a subset of peritubular capillaries; however, the significance of these cells is unclear. The purpose of this study was to determine whether deletion of Flk1 in the Foxd1 stroma was important for renal development. To that end, we conditionally deleted Flk1 (critical for endothelial cell development) in the renal stroma by breeding-floxed Flk1 mice (Flk1fl/fl ) with Foxd1cre mice to generate Foxd1cre; Flk1fl/fl (Flk1ST-/- ) mice. We then performed FACsorting, histological, morphometric, and metabolic analyses of Flk1ST-/- vs. control mice. We confirmed decreased expression of endothelial markers in the renal stroma of Flk1ST-/- kidneys via flow sorting and immunostaining, and upon interrogation of embryonic and postnatal Flk1ST-/- mice, we found they had dilated peritubular capillaries. Three-dimensional reconstructions showed reduced ureteric branching and fewer nephrons in developing Flk1ST-/- kidneys vs. Juvenile Flk1ST-/- kidneys displayed renal papillary hypoplasia and a paucity of collecting ducts. Twenty-four-hour urine collections revealed that postnatal Flk1ST-/- mice had urinary-concentrating defects. Thus, while lineage-tracing revealed that the renal cortical stroma gave rise to a small subset of endothelial progenitors, these Flk1-expressing stromal cells are critical for patterning the peritubular capillaries. Also, loss of Flk1 in the renal stroma leads to nonautonomous-patterning defects in ureteric lineages. Copyright © 2017 the American Physiological Society.

  8. Influence of visual angle on pattern reversal visual evoked potentials

    Directory of Open Access Journals (Sweden)

    Ruchi Kothari

    2014-01-01

    Full Text Available Purpose: The aim of this study was to find whether the visual evoked potential (VEP latencies and amplitude are altered with different visual angles in healthy adult volunteers or not and to determine the visual angle which is the optimum and most appropriate among a wide range of check sizes for the reliable interpretation of pattern reversal VEPs (PRVEPs. Materials and Methods: The present study was conducted on 40 healthy volunteers. The subjects were divided into two groups. One group consisted of 20 individuals (nine males and 11 females in the age range of 25-57 years and they were exposed to checks subtending a visual angle of 90, 120, and 180 minutes of arc. Another group comprised of 20 individuals (10 males and 10 females in the age range of 36-60 years and they were subjected to checks subtending a visual angle of 15, 30, and 120 minutes of arc. The stimulus configuration comprised of the transient pattern reversal method in which a black and white checker board is generated (full field on a VEP Monitor by an Evoked Potential Recorder (RMS EMG. EPMARK II. The statistical analysis was done by One Way Analysis of Variance (ANOVA using EPI INFO 6. Results: In Group I, the maximum (max. P100 latency of 98.8 ± 4.7 and the max. P100 amplitude of 10.05 ± 3.1 μV was obtained with checks of 90 minutes. In Group II, the max. P100 latency of 105.19 ± 4.75 msec as well as the max. P100 amplitude of 8.23 ± 3.30 μV was obtained with 15 minutes. The min. P100 latency in both the groups was obtained with checks of 120 minutes while the min. P100 amplitude was obtained with 180 minutes. A statistically significant difference was derived between means of P100 latency for 15 and 30 minutes with reference to its value for 120 minutes and between the mean value of P100 amplitude for 120 minutes and that of 90 and 180 minutes. Conclusion: Altering the size of stimulus (visual angle has an effect on the PRVEP parameters. Our study found that the 120

  9. Oxidative stress induced pulmonary endothelial cell proliferation is ...

    African Journals Online (AJOL)

    Cellular hyper-proliferation, endothelial dysfunction and oxidative stress are hallmarks of the pathobiology of pulmonary hypertension. Indeed, pulmonary endothelial cells proliferation is susceptible to redox state modulation. Some studies suggest that superoxide stimulates endothelial cell proliferation while others have ...

  10. Endothelial dysfunction – A predictor of atherosclerosis | Chhabra ...

    African Journals Online (AJOL)

    Endothelial dysfunction is a systemic disorder and a critical element in the pathogenesis of atherosclerotic diseases and its complications. Growing evidences suggest that the individual burden of currently known cardiovascular risk factors is not the only determinant of endothelial function; rather endothelial integrity ...

  11. Spreading endothelial cell dysfunction in response to necrotic trophoblasts. Soluble factors released from endothelial cells that have phagocytosed necrotic shed trophoblasts reduce the proliferation of additional endothelial cells.

    Science.gov (United States)

    Chen, Q; Ding, J X; Liu, B; Stone, P; Feng, Y J; Chamley, L

    2010-11-01

    The pathogenesis of preeclampsia is not clear but the disease is characterised by systemic endothelial cell dysfunction that is considered to be triggered by a placental factor. Necrotic trophoblastic debris that is deported in the maternal blood is one possible placental trigger for preeclampsia. Syncytial knots were first associated with preeclampsia over 100 years ago. However, syncytial knots are very large and most are trapped in the pulmonary capillaries making it difficult to envisage how they could lead to widespread systemic endothelial cell dysfunction. This study was undertaken to examine whether conditioned medium from endothelial cells that have phagocytosed necrotic trophoblastic debris could adversely affect the proliferation or survival of fresh endothelial cells. Trophoblastic cellular debris, harvested from placental explants was added to endothelial cell monolayers directly or after induction of necrosis by freeze-thawing. Conditioned medium from the endothelial cell cultures was exposed to fresh endothelial cells and their proliferation measured by Alamar Blue, and CyQUANTNF cell proliferation assays. Endothelial cell death was examined by a fluorogenic caspase-3 activity assay and LDH release. Conditioned medium from endothelial cells that had phagocytosed necrotic but not apoptotic trophoblastic debris significantly inhibited the proliferation of fresh endothelial cells but did not induce their death. The conditioned medium also reduced cell-surface endoglin expression by fresh endothelial cells. These results confirm that phagocytosis of necrotic trophoblastic debris by endothelial cells results in the secretion of soluble factors that might explain how necrotic trophoblastic debris trapped in the pulmonary capillaries could induce systemic endothelial cell dysfunction. Copyright © 2010 Elsevier Ltd. All rights reserved.

  12. Slow excitatory synaptic potentials evoked by distension in myenteric descending interneurones of guinea-pig ileum

    Science.gov (United States)

    Thornton, P D J; Bornstein, J C

    2002-01-01

    The functional significance of the slow excitatory synaptic potentials (EPSPs) in myenteric neurones is unknown. We investigated this using intracellular recording from myenteric neurones in guinea-pig ileum, in vitro. In all, 121 neurones responded with fast EPSPs to distension of the intestine oral to the recording site. In 28 of these neurones, distension also evoked depolarizations similar to the slow EPSPs evoked by electrical stimulation in the same neurones. Intracellular injection of biocytin and immunohistochemistry revealed that neurones responding to distension with slow EPSPs were descending interneurones, which were immunoreactive for nitric oxide synthase (NOS). Other neurones, including inhibitory motor neurones and interneurones lacking NOS, did not respond to distension with slow EPSPs, but many had slow EPSPs evoked electrically. Slow EPSPs evoked electrically or by distension in NOS-immunoreactive descending interneurones were resistant to blockade of NK1 or NK3 tachykinin receptors (SR 140333, 100 nm; SR 142801, 100 nm, respectively) and group I metabotropic glutamate receptors (PHCCC, 10–30 μm), when the antagonists were applied in the recording chamber of a two-chambered organ bath. However, slow EPSPs evoked electrically in inhibitory motor neurones were substantially depressed by SR 140333 (100 nm). Blockade of synaptic transmission in the stimulation chamber of the organ bath abolished slow EPSPs evoked by distension, indicating that they arose from activity in interneurones, and not from anally directed, intrinsic sensory neurones. Thus, distension evokes slow EPSPs in a subset of myenteric neurones, which may be important for intestinal motility. PMID:11882690

  13. Transient Evoked and Distortion Product Otoacoustic Emissions in a Group of Neonates

    Science.gov (United States)

    Silva, Giovanna Cesar; Delecrode, Camila Ribas; Kemp, Adriana Tahara; Martins, Fabiana; Cardoso, Ana Claudia Vieira

    2015-01-01

    Introduction The most commonly used method in neonatal hearing screening programs is transient evoked otoacoustic emissions in the first stage of the process. There are few studies comparing transient evoked otoacoustic emissions with distortion product, but some authors have investigated the issue. Objective To correlate the results of transient evoked and distortion product otoacoustic emissions in a Brazilian maternity hospital. Methods This is a cross-sectional, comparative, and prospective study. The study included 579 newborns, ranging from 6 to 54 days of age, born in a low-risk maternity hospital and assessed for hearing loss. All neonates underwent hearing screening by transient evoked and distortion product otoacoustic emissions. The results were analyzed using the Spearman correlation test to relate the two procedures. Results The pass index on transient evoked otoacoustic emissions was 95% and on distortion product otoacoustic emissions was 91%. The comparison of the two procedures showed that 91% of neonates passed on both procedures, 4.5% passed only on transient evoked otoacoustic emissions, 0.5% passed only on distortion product otoacoustic emissions, and 4% failed on both procedures. The inferential analysis showed a significant strong positive relationship between the two procedures. Conclusion The failure rate was higher in distortion product otoacoustic emissions when compared with transient evoked; however, there was correlation between the results of the procedures. PMID:26157501

  14. Language impairment is reflected in auditory evoked fields.

    Science.gov (United States)

    Pihko, Elina; Kujala, Teija; Mickos, Annika; Alku, Paavo; Byring, Roger; Korkman, Marit

    2008-05-01

    Specific language impairment (SLI) is diagnosed when a child has problems in producing or understanding language despite having a normal IQ and there being no other obvious explanation. There can be several associated problems, and no single underlying cause has yet been identified. Some theories propose problems in auditory processing, specifically in the discrimination of sound frequency or rapid temporal frequency changes. We compared automatic cortical speech-sound processing and discrimination between a group of children with SLI and control children with normal language development (mean age: 6.6 years; range: 5-7 years). We measured auditory evoked magnetic fields using two sets of CV syllables, one with a changing consonant /da/ba/ga/ and another one with a changing vowel /su/so/sy/ in an oddball paradigm. The P1m responses for onsets of repetitive stimuli were weaker in the SLI group whereas no significant group differences were found in the mismatch responses. The results indicate that the SLI group, having weaker responses to the onsets of sounds, might have slightly depressed sensory encoding.

  15. Evoking Baldwin’s Blues: The Experience of Dislocated Listening

    Directory of Open Access Journals (Sweden)

    Rashida K. Braggs

    2015-09-01

    Full Text Available “It is only in his music [. . .] that the Negro in America has been able to tell his story. It is a story which otherwise has yet to be told and which no American is prepared to hear,” so wrote James Baldwin in “Many Thousands Gone.” Throughout his career, James Baldwin returned to this incomprehension of African-American experience. He continually privileged music in his literature, crafting his own literary blues to address it. Baldwin’s blues resonated even more powerfully and painfully for its emotional and geographical dislocation. In this article, Rashida K. Braggs argues that it was the combination of music, word, and migration that prompted Baldwin’s own deeper understanding. Exploring her term dislocated listening, Braggs investigates how listening to music while willfully dislocated from one’s cultural home prompts a deeper understanding of African-American experience. The distance disconcerts, leaving one more vulnerable, while music impels the reader, audience, and even Baldwin to identify with some harsh realities of African-American experience. Baldwin evokes the experience of dislocated listening in his life and in “Sonny’s Blues.” Braggs also creates an experience of dislocated listening through her video performance of Baldwin’s words, thus attempting to draw the reader as well into a more attuned understanding of African-American experience.

  16. Brain stem evoked response audiometry of former drug users.

    Science.gov (United States)

    Weich, Tainara Milbradt; Tochetto, Tania Maria; Seligman, Lilian

    2012-10-01

    Illicit drugs are known for their deleterious effects upon the central nervous system and more specifically for how they adversely affect hearing. This study aims to analyze and compare the hearing complaints and the results of brainstem evoked response audiometry (BERA) of former drug user support group goers. This is a cross-sectional non-experimental descriptive quantitative study. The sample consisted of 17 subjects divided by their preferred drug of use. Ten individuals were placed in the marijuana group (G1) and seven in the crack/cocaine group (G2). The subjects were further divided based on how long they had been using drugs: 1 to 5 years, 6 to 10 years, and over 15 years. They were interviewed, and assessed by pure tone audiometry, acoustic impedance tests, and BERA. No statistically significant differences were found between G1 and G2 or time of drug use in absolute latencies and interpeak intervals. However, only five of the 17 individuals had BERA results with adequate results for their ages. Marijuana and crack/cocaine may cause diffuse disorders in the brainstem and compromise the transmission of auditory stimuli regardless of how long these substances are used for.

  17. Analysis of visual evoked responses in multiple sclerosis.

    Science.gov (United States)

    Mallecourt, J; Chain, F; Leblanc, M; Lhermitte, F

    1980-12-01

    In Multiple Sclerosis (MS) the modification of the latency of visual evoked responses (VER's) shows sequels of the involvement of anterior optic tracts manifested by a retro-bulbar optic neuritis (RBON). This study was made on 102 patients with MS. The stimulus used the pattern reversal of a checkboard. The influence of the size and squares 8' and 20' chosen as stimulus has been first studied in patients with antecedents of RBON. Using the 8' squares, all eyes with a history of RBON had pathological VER's. When there is no clinical antecedent of RBON, this means of stimulation enabled us to detect sequels of RBON. In "definitive" and "probable" MS, 100% of patients had pathological VER's either for both eyes of a single eyes. In "possible" MS a sequel of RBON was demonstrated in 57% of this population without clinical antecedent of RBON. A correlation between VER's result and the ophthalmological examination (visual acuity, fundoscopic examination and acquired dyschromatopsie) was made. Although VER's are an excellent method for detecting the sequels of RBON in MS. VER's abnormalities have no etiological significance, they are observed in other neurological involvements of anterior optic tracts. These different points are discussed and a physiological interpretation of VER's abnormalities is proposed.

  18. Neurogenic vestibular evoked potentials using a tone pip auditory stimulus.

    Science.gov (United States)

    Papathanasiou, E S; Zamba-Papanicolaou, E; Pantziaris, M; Kleopas, K; Kyriakides, T; Papacostas, S; Pattichis, C; Iliopoulos, I; Piperidou, C

    2004-01-01

    To obtain neurogenic vestibular evoked potentials (NVESTEPs) with surface scalp recording using a tone pip auditory stimulus. Fourteen neurologically normal volunteers (Age range 26-45 years, 10 females and 4 males), and two patients with sensorineural hearing loss and possible multiple sclerosis respectively, were examined. Two channel recordings were obtained, the first channel being P3 referred to Fpz, and the second channel being P4 referred to Fpz. A 1 kHz tone pip stimulus with two cycles was delivered via headphones monoaurally with contralateral masking noise. A consistent negative wave with a mean absolute latency of 4.72 msec was obtained, which we have named N5. 25% of the ears tested had better responses at the ipsilateral parietal electrode. In the patient with bilateral sensorineural hearing loss, NVESTEPs was present, suggesting that the NVESTEP is not a cochlear response. In the patient with possible multiple sclerosis, an abnormal NVESTEP response and a normal BAEP response were found. Use of a tone-pip rather than a click auditory stimulus allows a lower click intensity to be used in the production of NVESTEP responses, leads to a shorter testing time, and is therefore more comfortable for the patient. This study adds to our impression that the NVESTEP may be a physiological response that can be used to assess the vestibular system and is different from the BAEP response. Further testing in patients with symptoms of dizziness and with disorders specific for the vestibular nerve is required.

  19. A Subspace Method for Dynamical Estimation of Evoked Potentials

    Directory of Open Access Journals (Sweden)

    Stefanos D. Georgiadis

    2007-01-01

    Full Text Available It is a challenge in evoked potential (EP analysis to incorporate prior physiological knowledge for estimation. In this paper, we address the problem of single-channel trial-to-trial EP characteristics estimation. Prior information about phase-locked properties of the EPs is assesed by means of estimated signal subspace and eigenvalue decomposition. Then for those situations that dynamic fluctuations from stimulus-to-stimulus could be expected, prior information can be exploited by means of state-space modeling and recursive Bayesian mean square estimation methods (Kalman filtering and smoothing. We demonstrate that a few dominant eigenvectors of the data correlation matrix are able to model trend-like changes of some component of the EPs, and that Kalman smoother algorithm is to be preferred in terms of better tracking capabilities and mean square error reduction. We also demonstrate the effect of strong artifacts, particularly eye blinks, on the quality of the signal subspace and EP estimates by means of independent component analysis applied as a prepossessing step on the multichannel measurements.

  20. Flash visual evoked potentials in diurnal birds of prey.

    Science.gov (United States)

    Dondi, Maurizio; Biaggi, Fabio; Di Ianni, Francesco; Dodi, Pier Luigi; Quintavalla, Fausto

    2016-01-01

    The objective of this pilot study was to evaluate the feasibility of Flash Visual Evoked Potentials (FVEPs) testing in birds of prey in a clinical setting and to describe the protocol and the baseline data for normal vision in this species. FVEP recordings were obtained from 6 normal adult birds of prey: n. 2 Harris's Hawks (Parabuteo unicinctus), n. 1 Lanner Falcon (Falco biarmicus), n. 2 Gyrfalcons (Falco rusticolus) and n. 1 Saker Falcon (Falco cherrug). Before carrying out VEP tests, all animals underwent neurologic and ophthalmic routine examination. Waveforms were analysed to identify reproducible peaks from random variation of baseline. At least three positive and negative peaks were highlighted in all tracks with elevated repeatability. Measurements consisted of the absolute and relative latencies of these peaks (P1, N1, P2, N2, P3, and N3) and their peak-to-peak amplitudes. Both the peak latency and wave morphology achieved from normal animals were similar to those obtained previously in other animal species. This test can be easily and safely performed in a clinical setting in birds of prey and could be useful for an objective assessment of visual function.

  1. Effect of pupil size on multifocal pattern visual evoked potentials.

    Science.gov (United States)

    Martins, Alessandra; Balachandran, Chandra; Klistorner, Alexander I; Graham, Stuart L; Billson, Francis A

    2003-08-01

    The purpose of this study was to investigate the influence of pupil diameter on the amplitude and latency of multifocal visual evoked potentials (mfVEP). The multifocal objective perimeter (Accumap; Objectivision) was used to stimulate the visual field at 56 sites extending to 32 degrees using a pseudo-random pattern stimulus. The mfVEP were recorded using bipolar occipital electrodes, 7 min/eye. Ten normal subjects were recruited from the community and one eye was randomly selected for testing. The mfVEP were recorded at four different pupil diameters (2 mm, 4 mm, 6 mm, 8 mm), obtained by applying tropicamide (0.5%) or pilocarpine (2%) in different dilutions. Appropriate refractive correction was provided to overcome cycloplegia and achieve a visual acuity of 6/7.5 or better. Analysis revealed that at most pupil diameters the normalized full field amplitude did not show significant variation, except at the most miotic pupil diameter (2 mm), where the amplitude became reduced, based on 2-way anova and Tukey's T method. There was, however, significant correlation between latency and pupil area (correlation coefficient: upper field -0.63, lower field -0.76). The results suggest that even in the presence of mydriatics or miotics, the mfVEP test can be used to assess diseases that affect amplitude, provided near correction is used. The interpretation of latency, however, must be made with caution, as a borderline conduction defect with a dilated pupil may appear normal.

  2. Responses evoked by a vestibular implant providing chronic stimulation.

    Science.gov (United States)

    Thompson, Lara A; Haburcakova, Csilla; Gong, Wangsong; Lee, Daniel J; Wall, Conrad; Merfeld, Daniel M; Lewis, Richard F

    2012-01-01

    Patients with bilateral vestibular loss experience dehabilitating visual, perceptual, and postural difficulties, and an implantable vestibular prosthesis that could improve these symptoms would be of great benefit to these patients. In previous work, we have shown that a one-dimensional, unilateral canal prosthesis can improve the vestibulooccular reflex (VOR) in canal-plugged squirrel monkeys. In addition to the VOR, the potential effects of a vestibular prosthesis on more complex, highly integrative behaviors, such as the perception of head orientation and posture have remained unclear. We tested a one-dimensional, unilateral prosthesis in a rhesus monkey with bilateral vestibular loss and found that chronic electrical stimulation partially restored the compensatory VOR and also that percepts of head orientation relative to gravity were improved. However, the one-dimensional prosthetic stimulation had no clear effect on postural stability during quiet stance, but sway evoked by head-turns was modestly reduced. These results suggest that not only can the implementation of a vestibular prosthesis provide partial restitution of VOR but may also improve perception and posture in the presence of bilateral vestibular hypofunction (BVH). In this review, we provide an overview of our previous and current work directed towards the eventual clinical implementation of an implantable vestibular prosthesis.

  3. Protocol to collect late latency auditory evoked potentials.

    Science.gov (United States)

    Ventura, Luzia Maria Pozzobom; Alvarenga, Kátia de Freitas; Costa Filho, Orozimbo Alves

    2009-01-01

    Long Latency Auditory Evoked Potentials (LLAEP) represents a number of electrical changes occurring in the central nervous system, resulting from stimulation of the auditory sensorial pathways. Many studies approach the use of these potentials controlling the artifact created by eye movement with the use of equipment with a large number of channels. However, what happens is very different in Brazilian clinical practice, where the equipment used has a very limited number of channels. to compare the two methods used to control the artifacts created by eye movements during LLAEP capture using two recording channels. this is a prospective study with the application of two LLAEP capturing methods (eye artifact subtraction and rejection limit control) in 10 normal hearing individuals. we did not observe statistically significant differences concerning the latency values obtained with the use of both methods, only concerning amplitude values. both methods were efficient to capture the LLAEP and to control the eye movement artifact. The rejection limit control method produced greater amplitude values.

  4. Vestibular evoked myogenic potential in noise-induced hearing loss

    Directory of Open Access Journals (Sweden)

    Kaushlendra Kumar

    2010-01-01

    Full Text Available Noise affects one′s hearing as well as balance mechanism. The hearing mechanism of the noise-exposed individuals has been extensively studied. However, in view of the poor research focus on the sacculo-collic reflexes, especially in this study area, the present study was undertaken to examine the vestibular evoked myogenic potentials (VEMP in subjects with noise-induced hearing loss (NIHL. A total of 30 subjects (55 ears with NIHL participated in the present study within the age range of 30-40 years. VEMP recordings were done at 99 dBnHL using IHS instrument. The results indicated that as the average pure tone hearing threshold increased, the VEMP latencies were prolonged and peak to peak amplitude was reduced in NIHL subjects. Out of the 55 ears, VEMP was absent in 16 (29.0% ears. The latency was prolonged and the peak to peak amplitude was reduced in 19 (34.6% ears. VEMP results were normal in 20 (36.4% ears. Therefore, VEMP was abnormal or absent in 67% of NIHL subjects in the present study. Hence it can be concluded that the possibility of vestibular dysfunction, specially the saccular pathway, is high in individuals with NIHL. VEMP, a non-invasive and user friendly procedure, can be employed in these individuals to assess sacculo-collic reflex.

  5. Evoked cavernous activity: measuring penile autonomic innervation following pelvic surgery.

    Science.gov (United States)

    Yilmaz, U; Ellis, W; Lange, P; Yang, C

    2006-01-01

    To assess cavernous nerve integrity, we measured evoked cavernous activity (ECA) in 16 men who underwent nerve sparing radical prostatectomy (NS group) and 11 men who underwent non-nerve-sparing surgery (non-NS group). The right median nerve was electrically stimulated and ECA was recorded with two concentric electromyography needles placed into the right and left cavernous bodies. We simultaneously recorded hand and foot sympathetic skin responses (SSRs) as controls. All subjects had recordable SSR, and all subjects following nerve-sparing radical prostatectomy had reproducible ECA. Of the 11 non-NS subjects, eight had no response, indicating interrupted corporal innervation. Three subjects had reproducible ECA, one of whom had a very late latency, suggesting residual innervation was present. The mean latencies of ECA were similar to foot SSR mean latencies (P>0.05), but not to hand SSR latencies. The non-NS group was significantly different from the NS group for the presence of ECA (PECA is a viable method of evaluating the autonomic innervation of the penis.

  6. Early event related fields during visually evoked pain anticipation.

    Science.gov (United States)

    Gopalakrishnan, Raghavan; Burgess, Richard C; Plow, Ela B; Floden, Darlene P; Machado, Andre G

    2016-03-01

    Pain experience is not only a function of somatosensory inputs. Rather, it is strongly influenced by cognitive and affective pathways. Pain anticipatory phenomena, an important limitation to rehabilitative efforts in the chronic state, are processed by associative and limbic networks, along with primary sensory cortices. Characterization of neurophysiological correlates of pain anticipation, particularly during very early stages of neural processing is critical for development of therapeutic interventions. Here, we utilized magnetoencephalography to study early event-related fields (ERFs) in healthy subjects exposed to a 3 s visual countdown task that preceded a painful stimulus, a non-painful stimulus or no stimulus. We found that the first countdown cue, but not the last cue, evoked critical ERFs signaling anticipation, attention and alertness to the noxious stimuli. Further, we found that P2 and N2 components were significantly different in response to first-cues that signaled incoming painful stimuli when compared to non-painful or no stimuli. The findings indicate that early ERFs are relevant neural substrates of pain anticipatory phenomena and could be potentially serve as biomarkers. These measures could assist in the development of neurostimulation approaches aimed at curbing the negative effects of pain anticipation during rehabilitation. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  7. Vestibular evoked myogenic potentials in patients with ankylosing spondylitis.

    Science.gov (United States)

    Özgür, Abdulkadir; Serdaroğlu Beyazal, Münevver; Terzi, Suat; Coşkun, Zerrin Özergin; Dursun, Engin

    2016-10-01

    Ankylosing spondylitis (AS) is a chronic systemic inflammatory disease with unknown etiology. Although sacroiliac joint involvement is the classic sign along with the formed immune mediators, it may result in immune-mediated inner ear disease and may cause damage to the audiovestibular system. Vestibular evoked myogenic potentials (VEMP) is a clinical reflex test used in the diagnosis of vestibular diseases and is performed by recording and evaluating the muscle potentials resulting from the stimulation of the vestibular system with different stimuli. The aim of this study is to evaluate the cervical VEMP test results in AS patients without vestibular symptoms. Thirty-three patients with AS and a control group of 30 healthy volunteers with similar demographic characteristics were evaluated in the study. VEMP wave latency, P13-N23 wave amplitude, and VEMP asymmetry ratio (VAR) values were compared between the groups. The relationship between clinical and laboratory findings of the AS patients and VEMP data were also investigated. Compared with healthy people, this study shows the response rate of patients with ankylosing spondylitis was reduced in the VEMP test, and P13-N23 wave amplitude showed a decrease in AS patients who had VEMP response (p ankylosing spondylitis. The data obtained from this study suggest that AS may lead to decreased sensitivity of the vestibular system.

  8. An evoked potential mapping of transcallosal projections in the cat

    Directory of Open Access Journals (Sweden)

    A. Cukiert

    1989-03-01

    Full Text Available In ten adult cats anesthetized with ketamine hydrochloride the neocortex was exposed and rectangular pulses (1msec, 0.5 Hz and variable intensity were applied to discrete points of one side and transcallosal evoked potentials were recorded from the other. The stimulation and recording positions were determined on a cartesian map of most of the exposable neocortical areas and the potentials were analysed as to their components, voltage and latency. Passive spread and electrotonic potentials and the effects of increasing frequency were also analysed. The results showed large transcallosal potentials in some areas and an increase of potentials in the caudorostral direction, attaining the highest values in anteromedial areas of the suprasylvian gyrus. Confirming anatomical studies, a few silent spots were found in the motor and somesthetic cortex and in restricted posterior regions of the visual cortex, where small or zero voltages occurred. While causing weak contralateral potentials, stimulation of some posterior sites provoked high voltage potentials in anterior regions of the side being stimulated and in the corresponding area of the opposite site. These posterior sites are. poorly interconnected by the corpus callosum. The L-shaped indirect connection described in this work may be involved in some types of epilepsy and may explain the effectiveness of partial callosotomy in their treatment.

  9. Ocular Vestibular Evoked Myogenic Potentials: Where Are We Now?

    Science.gov (United States)

    Dlugaiczyk, Julia

    2017-12-01

    Over the last decade, ocular vestibular evoked myogenic potentials (oVEMPs) have evolved as a new clinical test for dynamic otolith (predominantly utricular) function. The aim of this review is to give an update on the neurophysiological foundations of oVEMPs and their implications for recording and interpreting oVEMP responses in clinical practice. Different lines of anatomical, neurophysiological, and clinical evidence support the notion that oVEMPs measure predominantly contralateral utricular function, while cervical cVEMPs are an indicator of ipsilateral saccular function. Bone-conducted vibration (BCV) in the midline of the forehead at the hairline (Fz) or unilateral air-conducted sound (ACS) are commonly used as stimuli for oVEMPs. It is recommended to apply short stimuli with short rise times for obtaining optimal oVEMP responses. Finally, this review summarizes the clinical application and interpretation of oVEMPs, particularly for vestibular neuritis, Ménière's disease, superior canal dehiscence and "challenging" patients.

  10. Pattern Visual Evoked Potentials Elicited by Organic Electroluminescence Screen

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    Celso Soiti Matsumoto

    2014-01-01

    Full Text Available Purpose. To determine whether organic electroluminescence (OLED screens can be used as visual stimulators to elicit pattern-reversal visual evoked potentials (p-VEPs. Method. Checkerboard patterns were generated on a conventional cathode-ray tube (S710, Compaq Computer Co., USA screen and on an OLED (17 inches, 320 × 230 mm, PVM-1741, Sony, Tokyo, Japan screen. The time course of the luminance changes of each monitor was measured with a photodiode. The p-VEPs elicited by these two screens were recorded from 15 eyes of 9 healthy volunteers (22.0 ± 0.8 years. Results. The OLED screen had a constant time delay from the onset of the trigger signal to the start of the luminescence change. The delay during the reversal phase from black to white for the pattern was 1.0 msec on the cathode-ray tube (CRT screen and 0.5 msec on the OLED screen. No significant differences in the amplitudes of P100 and the implicit times of N75 and P100 were observed in the p-VEPs elicited by the CRT and the OLED screens. Conclusion. The OLED screen can be used as a visual stimulator to elicit p-VEPs; however the time delay and the specific properties in the luminance change must be taken into account.

  11. Development of Brainstem-Evoked Responses in Congenital Auditory Deprivation

    Directory of Open Access Journals (Sweden)

    J. Tillein

    2012-01-01

    Full Text Available To compare the development of the auditory system in hearing and completely acoustically deprived animals, naive congenitally deaf white cats (CDCs and hearing controls (HCs were investigated at different developmental stages from birth till adulthood. The CDCs had no hearing experience before the acute experiment. In both groups of animals, responses to cochlear implant stimulation were acutely assessed. Electrically evoked auditory brainstem responses (E-ABRs were recorded with monopolar stimulation at different current levels. CDCs demonstrated extensive development of E-ABRs, from first signs of responses at postnatal (p.n. day 3 through appearance of all waves of brainstem response at day 8 p.n. to mature responses around day 90 p.n.. Wave I of E-ABRs could not be distinguished from the artifact in majority of CDCs, whereas in HCs, it was clearly separated from the stimulus artifact. Waves II, III, and IV demonstrated higher thresholds in CDCs, whereas this difference was not found for wave V. Amplitudes of wave III were significantly higher in HCs, whereas wave V amplitudes were significantly higher in CDCs. No differences in latencies were observed between the animal groups. These data demonstrate significant postnatal subcortical development in absence of hearing, and also divergent effects of deafness on early waves II–IV and wave V of the E-ABR.

  12. Flash visual evoked potentials in diurnal birds of prey

    Directory of Open Access Journals (Sweden)

    Maurizio Dondi

    2016-07-01

    Full Text Available The objective of this pilot study was to evaluate the feasibility of Flash Visual Evoked Potentials (FVEPs testing in birds of prey in a clinical setting and to describe the protocol and the baseline data for normal vision in this species. FVEP recordings were obtained from 6 normal adult birds of prey: n. 2 Harris’s Hawks (Parabuteo unicinctus, n. 1 Lanner Falcon (Falco biarmicus, n. 2 Gyrfalcons (Falco rusticolus and n. 1 Saker Falcon (Falco cherrug. Before carrying out VEP tests, all animals underwent neurologic and ophthalmic routine examination. Waveforms were analysed to identify reproducible peaks from random variation of baseline. At least three positive and negative peaks were highlighted in all tracks with elevated repeatability. Measurements consisted of the absolute and relative latencies of these peaks (P1, N1, P2, N2, P3, and N3 and their peak-to-peak amplitudes. Both the peak latency and wave morphology achieved from normal animals were similar to those obtained previously in other animal species. This test can be easily and safely performed in a clinical setting in birds of prey and could be useful for an objective assessment of visual function.

  13. Vestibular evoked myogenic potential findings in multiple sclerosis.

    Science.gov (United States)

    Escorihuela García, Vicente; Llópez Carratalá, Ignacio; Orts Alborch, Miguel; Marco Algarra, Jaime

    2013-01-01

    Multiple sclerosis is an inflammatory disease involving the occurrence of demyelinating, chronic neurodegenerative lesions in the central nervous system. We studied vestibular evoked myogenic potentials (VEMPs) in this pathology, to allow us to evaluate the saccule, inferior vestibular nerve and vestibular-spinal pathway non-invasively. There were 23 patients diagnosed with multiple sclerosis who underwent VEMP recordings, comparing our results with a control group consisting of 35 healthy subjects. We registered p13 and n23 wave latencies, interaural amplitude difference and asymmetry ratio between both ears. Subjects also underwent an otoscopy and audiometric examination. The prolongation of p13 and n23 wave latencies was the most notable characteristic, with a mean p13 wave latency of 19.53 milliseconds and a mean latency of 30.06 milliseconds for n23. In contrast, the asymmetry index showed no significant differences with our control group. In case of multiple sclerosis, the prolongation of the p13 and n23 VEMP wave latencies is a feature that has been attributed to slowing of conduction by demyelination of the vestibular-spinal pathway. In this regard, alteration of the response or lack thereof in these potentials has a locator value of injury to the lower brainstem. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  14. Transient and distortion product evoked otoacoustic emissions in premature infants

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    Oliveira, Carlos Augusto Costa Pires de

    2009-09-01

    Full Text Available Introduction: The correlation between the transient (TEOE and distortion product (DPOAE evoked otoacoustic emissions may be useful for the neonatal auditory screening, mainly in premature infants, who have risk indicators for hearing deficiency. There is need for deepening the knowledge regarding this population cochlea features. Objective: To compare the TEOE and DPOAE in premature infants. To analyze the reproducibility in the TEOE, the amplitude and the sign/noise ratio in the TEOE and DPOAE. Method: TEOE and DPOAE were carried out in 50 premature infants. The tests were correlated as for the criterion "pass/failure" and compared according to amplitude and sign/noise ratio parameters. Results: The TEOE were present in 71% of the sample. The frequency of 3kHz presented a better performance in the average reproducibility, amplitude and sign/noise ratio. The DPOAE were present in 97% of the sample. The frequency of 2kHz had a major average amplitude, the values of the sign/noise ratio increased proportionally in the high frequencies. There was a strong correlation between TEOE and DPOAE in the "pass/failure" criterion (p=0.006. Conclusion: The correlation between the TEOE and DPOAE results was significant. But one method compliments the other and both may be used in the TAN.

  15. Humor drawings evoked temporal and spectral EEG processes

    Science.gov (United States)

    Kuo, Hsien-Chu; Chuang, Shang-Wen

    2017-01-01

    Abstract The study aimed to explore the humor processing elicited through the manipulation of artistic drawings. Using the Comprehension–Elaboration Theory of humor as the main research background, the experiment manipulated the head portraits of celebrities based on the independent variables of facial deformation (large/small) and addition of affective features (positive/negative). A 64-channel electroencephalography was recorded in 30 participants while viewing the incongruous drawings of celebrities. The electroencephalography temporal and spectral responses were measured during the three stages of humor which included incongruity detection, incongruity comprehension and elaboration of humor. Analysis of event-related potentials indicated that for humorous vs non-humorous drawings, facial deformation and the addition of affective features significantly affected the degree of humor elicited, specifically: large > small deformation; negative > positive affective features. The N170, N270, N400, N600-800 and N900-1200 components showed significant differences, particularly in the right prefrontal and frontal regions. Analysis of event-related spectral perturbation showed significant differences in the theta band evoked in the anterior cingulate cortex, parietal region and posterior cingulate cortex; and in the alpha and beta bands in the motor areas. These regions are involved in emotional processing, memory retrieval, and laughter and feelings of amusement induced by elaboration of the situation. PMID:28402573

  16. ORIGINAL ARTICLE Relationship between endothelial nitric oxide ...

    African Journals Online (AJOL)

    salah

    Introduction: Endothelial nitric oxide synthase (eNOS), the enzyme in charge of nitric oxide production, plays a crucial role in vascular biology. However, the impact of single nucleotide polymorphisms (SNPs) affecting the gene encoding for eNOS (eNOS) on coronary artery diseases remains under debate and no data were ...

  17. Protective role of endothelial nitric oxide synthase

    NARCIS (Netherlands)

    Albrecht, Ester W J A; Stegeman, Coen A; Heeringa, Peter; Henning, Robert; van Goor, Harry

    Nitric oxide is a versatile molecule, with its actions ranging from haemodynamic regulation to anti-proliferative effects on vascular smooth muscle cells. Nitric oxide is produced by the nitric oxide synthases, endothelial NOS (eNOS), neural NOS (nNOS), and inducible NOS (iNOS). Constitutively

  18. Relationship between endothelial nitric oxide synthase gene ...

    African Journals Online (AJOL)

    Introduction: Endothelial nitric oxide synthase (eNOS), the enzyme in charge of nitric oxide production, plays a crucial role in vascular biology. However, the impact of single nucleotide polymorphisms (SNPs) affecting the gene encoding for eNOS (eNOS) on coronary artery diseases remains under debate and no data were ...

  19. Endothelial derived hyperpolarization in renal interlobar arteries

    DEFF Research Database (Denmark)

    Brasen, Jens Christian; Sørensen, Charlotte M.

    2015-01-01

    In small arteries, vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) are connect by myoendothelial junctions (MEJ), usually extending from the EC. Ca2+ activated K+ channels (IKCa and SKCa) located in the MEJ are suggested to play a role in NO-independent endothelium derived...

  20. Endothelial cell oxidative stress and signal transduction

    Directory of Open Access Journals (Sweden)

    ROCIO FONCEA

    2000-01-01

    Full Text Available Endothelial dysfunction (ED is an early event in atherosclerotic disease, preceding clinical manifestations and complications. Increased reactive oxygen species (ROS have been implicated as important mechanisms that contribute to ED, and ROS’s may function as intracellular messengers that modulate signaling pathways. Several intracellular signal events stimulated by ROS have been defined, including the identification of two members of the mitogen activated protein kinase family (ERK1/2 and big MAP kinase, BMK1, tyrosine kinases (Src and Syk and different isoenzymes of PKC as redox-sensitive kinases. ROS regulation of signal transduction components include the modification in the activity of transcriptional factors such as NFkB and others that result in changes in gene expression and modifications in cellular responses. In order to understand the intracellular mechanisms induced by ROS in endothelial cells (EC, we are studying the response of human umbilical cord vein endothelial cells to increased ROS generation by different pro-atherogenic stimuli. Our results show that Homocysteine (Hcy and oxidized LDL (oxLDL enhance the activity and expression of oxidative stress markers, such as NFkB and heme oxygenase 1. These results suggest that these pro-atherogenic stimuli increase oxidative stress in EC, and thus explain the loss of endothelial function associated with the atherogenic process

  1. Endothelial nitric oxide synthase gene polymorphisms associated ...

    African Journals Online (AJOL)

    Endothelial nitric oxide synthase (NOS3) is involved in key steps of immune response. Genetic factors predispose individuals to periodontal disease. This study's aim was to explore the association between NOS3 gene polymorphisms and clinical parameters in patients with periodontal disease. Genomic DNA was obtained ...

  2. Endothelial Changes in Individuals with Prehypertension.

    Science.gov (United States)

    Valente, Flavia Mariana; Vespasiano, Patricia; Barbosa, Juliana Aparecida; Cesarino, Claudia Bernardi; de Andrade, Days Oliveira; Barufi Fernandes, Leticia Aparecida; Cosenso-Martin, Luciana Neves; Balduino-Mendes, Alessandra Beatriz; Gaglianone, Camila; Vilela-Martin, José Fernando

    2016-01-01

    Prehypertension is considered a precursor of systemic arterial hypertension and a predictor of morbidity-mortality due to cardiovascular diseases, which are the main causes of death in Brazil and the world. Thus, early diagnosis and the adoption of therapeutic measures in cases of prehypertension can reduce cardiovascular risk. The aim of the present study was to perform a selective review of the literature to identify and discuss early endothelial changes in individuals with pre-hypertension. The findings indicate an increase in ET-1-mediated vasoconstrictor tone in prehypertension, with endothelial-dependent vasodilatation impairment. Moreover, significantly high levels of angiotensin, arginine and vasopressin were found in this group of patients. A reduction in endothelial fibrinolytic capacity was another important change found in patients with prehypertention and was associated with an increased risk for atherothrombotic events. The present findings demonstrate endothelial changes in individuals with prehypertension that contribute to the development of arterial hypertension as well as a high risk for cardiovascular events, underscoring the importance of the early adoption of optimized therapeutic measures for this population.

  3. Protective effects of vascular endothelial growth factor in cultured brain endothelial cells against hypoglycemia.

    Science.gov (United States)

    Zhao, Fei; Deng, Jiangshan; Yu, Xiaoyan; Li, Dawei; Shi, Hong; Zhao, Yuwu

    2015-08-01

    Hypoglycemia is a common and serious problem among patients with type 1 diabetes receiving treatment with insulin. Clinical studies have demonstrated that hypoglycemic edema is involved in the initiation of hypoglycemic brain damage. However, the mechanisms of this edema are poorly understood. Vascular endothelial growth factor (VEGF), a potent regulator of blood vessel function, has been observed an important candidate hormone induced by hypoglycemia to protect neurons by restoring plasma glucose. Whether VEGF has a protective effect against hypoglycemia-induced damage in brain endothelial cells is still unknown. To investigate the effects of hypoglycemia on cerebral microvascular endothelial cells and assess the protective effect of exogenous VEGF on endothelial cells during hypoglycemia, confluent monolayers of the brain endothelial cell line bEnd.3 were treated with normal (5.5 mM glucose), hypoglycemic (0, 0.5, 1 mM glucose) medium or hypoglycemic medium in the presence of VEGF. The results clearly showed that hypoglycemia significantly downregulated the expression of claudin-5 in bEnd.3 cells, without affecting ZO-1 and occludin expression and distribution. Besides, transendothelial permeability significantly increased under hypoglycemic conditions compared to that under control conditions. Moreover, the hypoglycemic medium in presence of VEGF decreased endothelial permeability via the inhibition of claudin-5 degradation and improved hypoglycemia-induced cell toxicity. Furthermore, Glucose transporter-1 (Glut-1) and apoptosis regulator Bcl-2 expression were significantly upregulated. Taken together, hypoglycemia can significantly increase paraendocellular permeability by downregulating claudin-5 expression. We further showed that VEGF protected brain endothelial cells against hypoglycemia by enhancing glucose passage, reducing endothelial cell death, and ameliorating paraendocellular permeability.

  4. Dobesilate enhances endothelial nitric oxide synthase-activity in macro- and microvascular endothelial cells.

    Science.gov (United States)

    Suschek, C; Kolb, H; Kolb-Bachofen, V

    1997-12-01

    1. Dobesilate is used for normalizing vascular dysfunction in a number of diseases. In search for an effect on endothelial NO production, macrovascular endothelial cells from rat aorta, microvascular endothelial cells from rat exocrine pancreatic tissue, and capillary endothelial cells from rat islets, were cultured in the presence or absence of Mg-Dobesilate. The activity of constitutive nitric oxide synthase (ecNOS) in resident cells as well as of inducible nitric oxide synthase (iNOS) in cytokine-activated cells was measured indirectly by recording the citrulline concentrations in culture supernatants. 2. In each of the different endothelial cells Mg-Dobesilate incubation (0.25-1 mM) for 24 h led to a significant and concentration-dependent increase in ecNOS-activities. With cytokine-activated endothelial cell cultures only moderate effects were seen with little or no concentration-dependency. Addition of the NOS-inhibitor N(G)-monomethyl-L-arginine led to a significant suppression of citrulline formation in all cultures as an evidence for the enzyme specificity of these effects. 3. iNOS- and ecNOS-specific reverse transcription and semi-quantitative polymerase chain reaction (RT-PCR) with RNA from resident or cytokine-activated endothelial cells gave no evidence for an increase in NOS-specific mRNA after Mg-Dobesilate-treatment. Furthermore, Dobesilate-mediated enhancement of NO synthesis in resting endothelial cells was not due to iNOS induction in these cells, as no iNOS-specific signal was found by RT-PCR.

  5. Using cultured endothelial cells to study endothelial barrier dysfunction: Challenges and opportunities

    OpenAIRE

    Aman, Jurjan; Weijers, Ester M.; Geerten P van Nieuw Amerongen; Malik, Asrar B.; van Hinsbergh, Victor W.M.

    2016-01-01

    Despite considerable progress in the understanding of endothelial barrier regulation and the identification of approaches that have the potential to improve endothelial barrier function, no drug- or stem cell-based therapy is presently available to reverse the widespread vascular leak that is observed in acute respiratory distress syndrome (ARDS) and sepsis. The translational gap suggests a need to develop experimental approaches and tools that better mimic the complex environment of the micr...

  6. Animal study on transplantation of human umbilical vein endothelial cells for corneal endothelial decompensation

    Directory of Open Access Journals (Sweden)

    Li Cui

    2014-06-01

    Full Text Available AIM: To explore the feasibility of culturing human umbilical vein endothelial cells(HUVECon acellular corneal stroma and performing the posterior lamellar endothelial keratoplasty(PLEKtreating corneal endothelial decompensation.METHODS: Thirty New-Zealand rabbits were divided into three groups randomly, 10 rabbits for experimental group, 10 for stroma group and 10 for control group. Corneal endothelial cells were removed to establish animal model of corneal endothelial failure. PLEK was performed on the rabbits of experimental group and stroma group, and nothing was transplantated onto the rabbits of control group with the deep layer excised only. Postoperative observation was taken for 3mo. The degree of corneal edema and central corneal thickness were recorded for statistical analysis.RESULTS: Corneas in experimental group were relieved in edema obviously compared with that in stroma group and the control group, and showed increased transparency 7d after the operation. The average density of endothelial cells was 2 026.4±129.3cells/mm2, and average central corneal thickness was 505.2±25.4μm in experimental group, while 1 535.6±114.5μm in stroma group and 1 493.5±70.2μm in control group 3mo after operation.CONCLUSION:We achieved preliminary success in our study that culturing HUVEC on acellular corneal stroma and performing PLEK for corneal endothelial decompensation. HUVEC transplanted could survive in vivo, and have normal biological function of keeping cornea transparent. This study provides a new idea and a new way clinically for the treatment of corneal endothelial diseases.

  7. Genetic Variation in the Platelet Endothelial Aggregation Receptor 1 Gene Results in Endothelial Dysfunction.

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    Adam S Fisch

    Full Text Available Platelet Endothelial Aggregation Receptor 1 (PEAR1 is a newly identified membrane protein reported to be involved in multiple vascular and thrombotic processes. While most studies to date have focused on the effects of this receptor in platelets, PEAR1 is located in multiple tissues including the endothelium, where it is most highly expressed. Our first objective was to evaluate the role of PEAR1 in endothelial function by examining flow-mediated dilation of the brachial artery in 641 participants from the Heredity and Phenotype Intervention Heart Study. Our second objective was to further define the impact of PEAR1 on cardiovascular disease computationally through meta-analysis of 75,000 microarrays, yielding insights regarding PEAR1 function, and predictions of phenotypes and diseases affected by PEAR1 dysregulation. Based on the results of this meta-analysis we examined whether genetic variation in PEAR1 influences endothelial function using an ex vivo assay of endothelial cell migration. We observed a significant association between rs12041331 and flow-mediated dilation in participants of the Heredity and Phenotype Intervention Heart Study (P = 0.02. Meta-analysis results revealed that PEAR1 expression is highly correlated with several genes (e.g. ANG2, ACVRL1, ENG and phenotypes (e.g. endothelial cell migration, angiogenesis that are integral to endothelial function. Functional validation of these results revealed that PEAR1 rs12041331 is significantly associated with endothelial migration (P = 0.04. Our results suggest for the first time that genetic variation of PEAR1 is a significant determinant of endothelial function through pathways implicated in cardiovascular disease.

  8. Anesthetic propofol overdose causes endothelial cytotoxicity in vitro and endothelial barrier dysfunction in vivo

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    Lin, Ming-Chung [Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China); Department of Anesthesiology, Chi Mei Medical Center, Liouying, Tainan, Taiwan (China); Chen, Chia-Ling [Center of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China); Yang, Tsan-Tzu; Choi, Pui-Ching [Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China); Hsing, Chung-Hsi [Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan (China); Department of Anesthesiology, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Lin, Chiou-Feng, E-mail: cflin@mail.ncku.edu.tw [Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China); Center of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China); Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China); Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China)

    2012-12-01

    An overdose and a prolonged treatment of propofol may cause cellular cytotoxicity in multiple organs and tissues such as brain, heart, kidney, skeletal muscle, and immune cells; however, the underlying mechanism remains undocumented, particularly in vascular endothelial cells. Our previous studies showed that the activation of glycogen synthase kinase (GSK)-3 is pro-apoptotic in phagocytes during overdose of propofol treatment. Regarding the intravascular administration of propofol, we therefore hypothesized that propofol overdose also induces endothelial cytotoxicity via GSK-3. Propofol overdose (100 μg/ml) inhibited growth in human arterial and microvascular endothelial cells. After treatment, most of the endothelial cells experienced caspase-independent necrosis-like cell death. The activation of cathepsin D following lysosomal membrane permeabilization (LMP) determined necrosis-like cell death. Furthermore, propofol overdose also induced caspase-dependent apoptosis, at least in part. Caspase-3 was activated and acted downstream of mitochondrial transmembrane potential (MTP) loss; however, lysosomal cathepsins were not required for endothelial cell apoptosis. Notably, activation of GSK-3 was essential for propofol overdose-induced mitochondrial damage and apoptosis, but not necrosis-like cell death. Intraperitoneal administration of a propofol overdose in BALB/c mice caused an increase in peritoneal vascular permeability. These results demonstrate the cytotoxic effects of propofol overdose, including cathepsin D-regulated necrosis-like cell death and GSK-3-regulated mitochondrial apoptosis, on endothelial cells in vitro and the endothelial barrier dysfunction by propofol in vivo. Highlights: ► Propofol overdose causes apoptosis and necrosis in endothelial cells. ► Propofol overdose triggers lysosomal dysfunction independent of autophagy. ► Glycogen synthase kinase-3 facilitates propofol overdose-induced apoptosis. ► Propofol overdose causes an increase

  9. Corneal donor tissue preparation for endothelial keratoplasty.

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    Woodward, Maria A; Titus, Michael; Mavin, Kyle; Shtein, Roni M

    2012-06-12

    Over the past ten years, corneal transplantation surgical techniques have undergone revolutionary changes. Since its inception, traditional full thickness corneal transplantation has been the treatment to restore sight in those limited by corneal disease. Some disadvantages to this approach include a high degree of post-operative astigmatism, lack of predictable refractive outcome, and disturbance to the ocular surface. The development of Descemet's stripping endothelial keratoplasty (DSEK), transplanting only the posterior corneal stroma, Descemet's membrane, and endothelium, has dramatically changed treatment of corneal endothelial disease. DSEK is performed through a smaller incision; this technique avoids 'open sky' surgery with its risk of hemorrhage or expulsion, decreases the incidence of postoperative wound dehiscence, reduces unpredictable refractive outcomes, and may decrease the rate of transplant rejection. Initially, cornea donor posterior lamellar dissection for DSEK was performed manually resulting in variable graft thickness and damage to the delicate corneal endothelial tissue during tissue processing. Automated lamellar dissection (Descemet's stripping automated endothelial keratoplasty, DSAEK) was developed to address these issues. Automated dissection utilizes the same technology as LASIK corneal flap creation with a mechanical microkeratome blade that helps to create uniform and thin tissue grafts for DSAEK surgery with minimal corneal endothelial cell loss in tissue processing. Eye banks have been providing full thickness corneas for surgical transplantation for many years. In 2006, eye banks began to develop methodologies for supplying precut corneal tissue for endothelial keratoplasty. With the input of corneal surgeons, eye banks have developed thorough protocols to safely and effectively prepare posterior lamellar tissue for DSAEK surgery. This can be performed preoperatively at the eye bank. Research shows no significant difference in

  10. Selective endothelial overexpression of arginase II induces endothelial dysfunction and hypertension and enhances atherosclerosis in mice.

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    Boris L Vaisman

    Full Text Available Cardiovascular disorders associated with endothelial dysfunction, such as atherosclerosis, have decreased nitric oxide (NO bioavailability. Arginase in the vasculature can compete with eNOS for L-arginine and has been implicated in atherosclerosis. The aim of this study was to evaluate the effect of endothelial-specific elevation of arginase II expression on endothelial function and the development of atherosclerosis.Transgenic mice on a C57BL/6 background with endothelial-specific overexpression of human arginase II (hArgII gene under the control of the Tie2 promoter were produced. The hArgII mice had elevated tissue arginase activity except in liver and in resident peritoneal macrophages, confirming endothelial specificity of the transgene. Using small-vessel myography, aorta from these mice exhibited endothelial dysfunction when compared to their non-transgenic littermate controls. The blood pressure of the hArgII mice was 17% higher than their littermate controls and, when crossed with apoE -/- mice, hArgII mice had increased aortic atherosclerotic lesions.We conclude that overexpression of arginase II in the endothelium is detrimental to the cardiovascular system.

  11. Deep lamellar endothelial keratoplasty (DLEK): pursuing the ideal goals of endothelial replacement.

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    Terry, M A

    2003-11-01

    Endothelial dysfunction is a leading cause of corneal vision loss and treatment requires surgical replacement with donor endothelium. Standard penetrating keratoplasty (PK) suffers from the inherent problems of surface corneal incisions and sutures and poor wound healing of vertical stromal wounds. This often results in high irregular astigmatism, unpredictable corneal power, and the risk of long-term visual loss from suture-induced vascularization, ulceration, rejection, and late wound rupture. This paper delineates five ideal goals of endothelial replacement, which include: (1) a smooth surface topography without significant change in astigmatism from preoperative to postoperative; (2) a highly predictable and stable corneal power; (3) a healthy donor endothelium that resolves all oedema; (4) a tectonically stable globe, safe from injury and infection; and (5) an optically pure cornea. Deep lamellar endothelial keratoplasty (DLEK) is a surgical method of endothelial replacement that is performed through a limbal scleral incision that leaves the surface of the recipient cornea untouched. The early results of this innovative surgery are discussed and compared to the results of PK in terms of fulfillment of the five ideal goals of endothelial replacement. With further refinement of interface creation, DLEK surgery may be the ideal method for endothelial replacement.

  12. Rapid induction of neutrophil-endothelial adhesion by endothelial complement fixation.

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    Marks, R M; Todd, R F; Ward, P A

    1989-05-25

    The adhesion of neutrophils to vascular endothelium is an early event in their recruitment into acute inflammatory lesions. In evaluating potential neutrophil-endothelial adhesive mechanisms in acute inflammation, important considerations are that adhesion in vivo may occur very rapidly following injury and that the specificity of the reaction resides in altered endothelium. That is, neutrophils adhere only to altered endothelium adjacent to an inflammatory focus, rather than at random as would be expected if activation of neutrophils were the initiator of adhesion. We have explored a possible bridging role for complement in causing early neutrophil-endothelial cell adhesion. The complement system is involved in inflammatory processes, is capable of rapid amplification, and endothelial complement fixation at sites of inflammation could generate an endothelium-restricted signal for neutrophil adhesion. We have now developed a model in which this can be investigated without complicating factors such as immunoglobulin deposition, by constructing a novel molecule, a hybrid of the endothelial binding lectin Ulex europaeus I and of the complement activator cobra venom factor. This molecule has the capacity to cause fixation of complement on human umbilical vein endothelial cells. We show that complement fixation is a potent and rapid stimulus for neutrophil adhesion. Neutrophil adhesion requires only endothelial deposition of C3, and is mediated through the type 3 complement receptor.

  13. Early Stress Evokes Age-Dependent Biphasic Changes in Hippocampal Neurogenesis, Bdnf Expression, and Cognition

    Science.gov (United States)

    Suri, Deepika; Veenit, Vandana; Sarkar, Ambalika; Thiagarajan, Devi; Kumar, Arvind; Nestler, Eric J.; Galande, Sanjeev; Vaidya, Vidita A.

    2014-01-01

    Background Adult-onset stressors exert opposing effects on hippocampal neurogenesis and cognition, with enhancement observed following mild stress and dysfunction following severe chronic stress. While early life stress evokes persistent changes in anxiety, it is unknown whether early stress differentially regulates hippocampal neurogenesis, trophic factor expression, and cognition across the life span. Methods Hippocampal-dependent cognitive behavior, neurogenesis, and epigenetic regulation of brain-derived neurotrophic factor (Bdnf) expression was examined at distinct time points across the life span in rats subjected to the early stress of maternal separation (ES) and control groups. We also examined the influence of chronic antidepressant treatment on the neurogenic, neurotrophic, and cognitive changes in middle-aged ES animals. Results Animals subjected to early stress of maternal separation examined during postnatal life and young adulthood exhibited enhanced hippocampal neurogenesis, decreased repressive histone methylation at the Bdnf IV promoter along with enhanced Bdnf levels, and improved performance on the stress-associated Morris water maze. Strikingly, opposing changes in hippocampal neurogenesis and epigenetic regulation of Bdnf IV expression, concomitant with impairments on hippocampal-dependent cognitive tasks, were observed in middle-aged ES animals. Chronic antidepressant treatment with amitriptyline attenuated the maladaptive neurogenic, epigenetic, transcriptional, and cognitive effects in middle-aged ES animals. Conclusions Our study provides novel insights into the short- and long-term consequences of ES, demonstrating both biphasic and unique, age-dependent changes at the molecular, epigenetic, neurogenic, and behavioral levels. These results indicate that early stress may transiently endow animals with a potential adaptive advantage in stressful environments but across a life span is associated with long-term deleterious effects. PMID

  14. CGRPα-expressing sensory neurons respond to stimuli that evoke sensations of pain and itch.

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    Eric S McCoy

    Full Text Available Calcitonin gene-related peptide (CGRPα, encoded by Calca is a classic marker of nociceptive dorsal root ganglia (DRG neurons. Despite years of research, it is unclear what stimuli these neurons detect in vitro or in vivo. To facilitate functional studies of these neurons, we genetically targeted an axonal tracer (farnesylated enhanced green fluorescent protein; GFP and a LoxP-stopped cell ablation construct (human diphtheria toxin receptor; DTR to the Calca locus. In culture, 10-50% (depending on ligand of all CGRPα-GFP-positive (+ neurons responded to capsaicin, mustard oil, menthol, acidic pH, ATP, and pruritogens (histamine and chloroquine, suggesting a role for peptidergic neurons in detecting noxious stimuli and itch. In contrast, few (2.2±1.3% CGRPα-GFP(+ neurons responded to the TRPM8-selective cooling agent icilin. In adult mice, CGRPα-GFP(+ cell bodies were located in the DRG, spinal cord (motor neurons and dorsal horn neurons, brain and thyroid-reproducibly marking all cell types known to express Calca. Half of all CGRPα-GFP(+ DRG neurons expressed TRPV1, ∼25% expressed neurofilament-200, <10% contained nonpeptidergic markers (IB4 and Prostatic acid phosphatase and almost none (<1% expressed TRPM8. CGRPα-GFP(+ neurons innervated the dorsal spinal cord and innervated cutaneous and visceral tissues. This included nerve endings in the epidermis and on guard hairs. Our study provides direct evidence that CGRPα(+ DRG neurons respond to agonists that evoke pain and itch and constitute a sensory circuit that is largely distinct from nonpeptidergic circuits and TRPM8(+/cool temperature circuits. In future studies, it should be possible to conditionally ablate CGRPα-expressing neurons to evaluate sensory and non-sensory functions for these neurons.

  15. Pleasure for visual and olfactory stimuli evoking energy-dense foods is decreased in anorexia nervosa.

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    Jiang, Tao; Soussignan, Robert; Rigaud, Daniel; Schaal, Benoist

    2010-11-30

    Although patients with anorexia nervosa have been suggested to be anhedonic, few experiments have directly measured their sensory pleasure for a range of food and non-food stimuli. This study aimed to examine whether restrictive anorexia nervosa (AN-R) patients displayed: i) a generalized decline in sensory pleasure or only in food-related sensory pleasure; ii) a modification of hedonic responses to food cues (liking) and of the desire to eat foods (wanting) as a function of their motivational state (hunger vs. satiety) and energy density of foods (high vs. low). Forty-six female participants (AN-R n=17; healthy controls (HC) n=29) reported before/after lunch their pleasure for pictures/odorants representing foods of different energy density and non-food objects. They also reported their desire to eat the foods evoked by the sensory stimuli, and completed the Physical Anhedonia Scale and the Beck Depression Inventory. AN-R and HC participants did not differ on liking ratings when exposed to low energy-density food or to non-food stimuli. The two groups also had similar physical anhedonia scores. However, compared to HC, AN-R reported lower liking ratings for high energy food pictures regardless of their motivational state. Olfactory pleasure was reduced only during the pre-prandial state in the AN-R group. The wanting ratings showed a distinct pattern since AN-R participants reported less desire to eat the foods representing both low and high energy densities, but the effect was restricted to the pre-prandial state. Taken together these results reflect more the influence of core symptoms in anorexia nervosa (fear of gaining weight) than an overall inability to experience pleasure. Copyright © 2010 Elsevier Ltd. All rights reserved.

  16. Frontal phasic and oscillatory generators of the N30 somatosensory evoked potential.

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    Cebolla, A M; Palmero-Soler, E; Dan, B; Cheron, G

    2011-01-15

    The N30 component of somatosensory evoked potentials has been recognized as a crucial index of brain sensorimotor processing and has been increasingly used clinically. Previously, we have shown that the N30 is accompanied by both an increase of the power spectrum of the ongoing beta-gamma EEG (event related synchronization, ERS) and by a reorganization (phase-locking) of the spontaneous phase of this rhythm (inter-trials coherency, ITC). In order to localize its sources taking into account both the phasic and oscillatory aspects of the phenomenon, we here apply swLORETA methods on averaged signals of the event-related potential (ERP) from a 128 scalp-electrodes array in time domain and also on raw EEG signals in frequency domain at the N30 peak latency. We demonstrate that the two different mechanisms that generate the N30 component power increase (ERS) and phase locking (ITC) across EEG trials are spatially localized in overlapping areas in the precentral cortex, namely the motor cortex (BA4) and the premotor cortex (BA6). From this common region, the generator of the N30 event-related potential expands toward the posterior part of BA4, the anterior part of BA6 and the prefrontal cortex (BA9). These latter areas also present significant ITC sources in the beta-gamma frequency range, but without significant power increase of this rhythm. This demonstrates that N30 results from network activity that depends on distinct oscillating and phasic generators localized in the frontal cortex. Copyright © 2010 Elsevier Inc. All rights reserved.

  17. Neural Circuitry that Evokes Escape Behavior upon Activation of Nociceptive Sensory Neurons in Drosophila Larvae.

    Science.gov (United States)

    Yoshino, Jiro; Morikawa, Rei K; Hasegawa, Eri; Emoto, Kazuo

    2017-08-21

    Noxious stimuli trigger a stereotyped escape response in animals. In Drosophila larvae, class IV dendrite arborization (C4 da) sensory neurons in the peripheral nervous system are responsible for perception of multiple nociceptive modalities, including noxious heat and harsh mechanical stimulation, through distinct receptors [1-9]. Silencing or ablation of C4 da neurons largely eliminates larval responses to noxious stimuli [10-12], whereas optogenetic activation of C4 da neurons is sufficient to provoke corkscrew-like rolling behavior similar to what is observed when larvae receive noxious stimuli, such as high temperature or harsh mechanical stimulation [10-12]. The receptors and the regulatory mechanisms for C4 da activation in response to a variety of noxious stimuli have been well studied [13-23], yet how C4 da activation triggers the escape behavior in the circuit level is still incompletely understood. Here we identify segmentally arrayed local interneurons (medial clusters of C4 da second-order interneurons [mCSIs]) in the ventral nerve cord that are necessary and sufficient to trigger rolling behavior. GFP reconstitution across synaptic partners (GRASP) analysis indicates that C4 da axons form synapses with mCSI dendrites. Optogenetic activation of mCSIs induces the rolling behavior, whereas silencing mCSIs reduces the probability of rolling behavior upon C4 da activation. Further anatomical and functional studies suggest that the C4 da-mCSI nociceptive circuit evokes rolling behavior at least in part through segmental nerve a (SNa) motor neurons. Our findings thus uncover a local circuit that promotes escape behavior upon noxious stimuli in Drosophila larvae and provide mechanistic insights into how noxious stimuli are transduced into the stereotyped escape behavior in the circuit level. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Electrically evoked compound action potentials artefact rejection by independent component analysis: procedure automation.

    Science.gov (United States)

    Akhoun, Idrick; McKay, Colette; El-Deredy, Wael

    2015-01-15

    Independent-components-analysis (ICA) successfully separated electrically-evoked compound action potentials (ECAPs) from the stimulation artefact and noise (ECAP-ICA, Akhoun et al., 2013). This paper shows how to automate the ECAP-ICA artefact cancellation process. Raw-ECAPs without artefact rejection were consecutively recorded for each stimulation condition from at least 8 intra-cochlear electrodes. Firstly, amplifier-saturated recordings were discarded, and the data from different stimulus conditions (different current-levels) were concatenated temporally. The key aspect of the automation procedure was the sequential deductive source categorisation after ICA was applied with a restriction to 4 sources. The stereotypical aspect of the 4 sources enables their automatic classification as two artefact components, a noise and the sought ECAP based on theoretical and empirical considerations. The automatic procedure was tested using 8 cochlear implant (CI) users and one to four stimulus electrodes. The artefact and noise sources were successively identified and discarded, leaving the ECAP as the remaining source. The automated ECAP-ICA procedure successfully extracted the correct ECAPs compared to standard clinical forward masking paradigm in 22 out of 26 cases. ECAP-ICA does not require extracting the ECAP from a combination of distinct buffers as it is the case with regular methods. It is an alternative that does not have the possible bias of traditional artefact rejections such as alternate-polarity or forward-masking paradigms. The ECAP-ICA procedure bears clinical relevance, for example as the artefact rejection sub-module of automated ECAP-threshold detection techniques, which are common features of CI clinical fitting software. Copyright © 2014. Published by Elsevier B.V.

  19. Music-evoked emotions: principles, brain correlates, and implications for therapy.

    Science.gov (United States)

    Koelsch, Stefan

    2015-03-01

    This paper describes principles underlying the evocation of emotion with music: evaluation, resonance, memory, expectancy/tension, imagination, understanding, and social functions. Each of these principles includes several subprinciples, and the framework on music-evoked emotions emerging from these principles and subprinciples is supposed to provide a starting point for a systematic, coherent, and comprehensive theory on music-evoked emotions that considers both reception and production of music, as well as the relevance of emotion-evoking principles for music therapy. © 2015 New York Academy of Sciences.

  20. [Present situation and development of ocular vestibular-evoked myogenic potential].

    Science.gov (United States)

    Hu, Juan; Xu, Min; Zhang, Qing

    2013-04-01

    Myogenic potentials evoked by air conducted sound (ACS), bone conducted vibration (BCV) or galvanic pulses can be recorded with surface electrodes over contracted muscles. These myogenic potentials are of vestibular origin (utricle and saccule) and so these potentials are called vestibular evoked myogenic potentials (VEMPs). Since the vestibular system has projections to many muscle systems, there are many such VEMPs. In this review, we discuss the generated origin, response pathway, waveform characteristics and clinical application of ocular vestibular-evoked myogenic potential (oVEMP).

  1. Endothelial progenitor cell biology in ankylosing spondylitis.

    Science.gov (United States)

    Verma, Inderjeet; Syngle, Ashit; Krishan, Pawan

    2015-03-01

    Endothelial progenitor cells (EPCs) are unique populations which have reparative potential in overcoming endothelial damage and reducing cardiovascular risk. Patients with ankylosing spondylitis (AS) have increased risk of cardiovascular morbidity and mortality. The aim of this study was to investigate the endothelial progenitor cell population in AS patients and its potential relationships with disease variables. Endothelial progenitor cells were measured in peripheral blood samples from 20 AS and 20 healthy controls by flow cytometry on the basis of CD34 and CD133 expression. Disease activity was evaluated by using Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Functional ability was monitored by using Bath Ankylosing Spondylitis Functional Index (BASFI). EPCs were depleted in AS patients as compared to healthy controls (CD34(+) /CD133(+) : 0.027 ± 0.010% vs. 0.044 ± 0.011%, P < 0.001). EPC depletions were significantly associated with disease duration (r = -0.52, P = 0.01), BASDAI (r = -0.45, P = 0.04) and C-reactive protein (r = -0.5, P = 0.01). This is the first study to demonstrate endothelial progenitor cell depletion in AS patients. EPC depletions inversely correlate with disease duration, disease activity and inflammation, suggesting the pivotal role of inflammation in depletion of EPCs. EPC would possibly also serve as a therapeutic target for preventing cardiovascular disease in AS. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  2. Endothelial dysfunction in rheumatic autoimmune diseases.

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    Murdaca, Giuseppe; Colombo, Barbara Maria; Cagnati, Paola; Gulli, Rossella; Spanò, Francesca; Puppo, Francesco

    2012-10-01

    Rheumatic autoimmune diseases have been associated with accelerated atherosclerosis and various types of vasculopathies. Atherosclerosis is an inflammatory condition which starts as a "response to injury" favoring endothelial dysfunction which is associated with increased expression of adhesion molecules, pro-inflammatory cytokines, pro-thrombotic factors, oxidative stress upregulation and abnormal vascular tone modulation. Endothelial dysfunction in rheumatic autoimmune diseases involves innate immune responses, including macrophages and dendritic cells expression of scavenger and toll-like receptors for modified or native LDL as well as neutrophil and complement activation, and dysregulation of adaptive immune responses, including proliferation of autoreactive T-helper-1 lymphocytes and defective function of dendritic and regulatory T cells. Specific differences for endothelial function among different disorders include: a) increased amounts of pro-atherogenic hormones, decreased amounts of anti-atherogenic hormones and increased insulin resistance in rheumatoid arthritis; b) autoantibodies production in systemic lupus erythematosus and antiphospholipid syndrome; c) smooth muscle cells proliferation, destruction of internal elastic lamina, fibrosis and coagulation and fibrinolytic system dysfunction in systemic sclerosis. Several self-antigens (i.e. high density lipoproteins, heat shock proteins, β2-glycoprotein1) and self-molecules modified by oxidative events (i.e. low density lipoproteins and oxidized hemoglobin) have been identified as targets of autoimmune responses. Endothelial dysfunction leads to accelerated atherosclerosis in rheumatoid arthritis, systemic lupus erythematosus and spondyloarthropaties whereas obliterative vasculopathy is associated with systemic sclerosis. In this paper, we will briefly review the most relevant information upon endothelial dysfunction and inflammatory mechanisms in atherosclerosis and we will summarize the similarities

  3. Corneal endothelial cytotoxicity of the Calotropis procera (ushaar) plant.

    Science.gov (United States)

    Al-Mezaine, Hani S; Al-Amry, Mohammed A; Al-Assiri, Abdullah; Fadel, Talal S; Tabbara, Khalid F; Al-Rajhi, Ali A

    2008-05-01

    To report 6 eyes of 5 patients with transient corneal edema after exposure to the milky latex of Calotropis procera (ushaar). Interventional case series. Intracorneal penetration of ushaar latex can lead to permanent endothelial cell loss with morphologic alteration. Corneal edema resolved completely in approximately 2 weeks in all cases, despite reduced endothelial cell count and abnormal morphology. Corneal endothelial toxicity of ushaar latex is caused by its ability to penetrate the corneal stroma and induce permanent loss of endothelial cells. Corneal edema resolves if sufficient endothelial cell viability is still present after resolution of ushaar keratitis.

  4. Relationship between the Phases of Sensory and Motor Activity during a Looming-Evoked Multistage Escape Behavior

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    Fotowat, Haleh; Gabbiani, Fabrizio

    2007-01-01

    The firing patterns of visual neurons tracking approaching objects need to be translated into appropriate motor activation sequences to generate escape behaviors. Locusts possess an identified neuron highly sensitive to approaching objects (looming stimuli), thought to play an important role in collision avoidance through its motor projections. To study how the activity of this neuron relates to escape behaviors, we monitored jumps evoked by looming stimuli in freely behaving animals. By comparing electrophysiological and high-speed video recordings, we found that the initial preparatory phase of jumps occurs on average during the rising phase of the firing rate of the looming-sensitive neuron. The coactivation period of leg flexors and extensors, which is used to store the energy required for the jump, coincides with the timing of the peak firing rate of the neuron. The final preparatory phase occurs after the peak and takeoff happens when the firing rate of the looming-sensitive neuron has decayed to <10% of its peak. Both the initial and the final preparatory phases and takeoff are triggered when the approaching object crosses successive threshold angular sizes on the animal’s retina. Our results therefore suggest that distinct phases of the firing patterns of individual sensory neurons may actively contribute to distinct phases of complex, multistage motor behaviors. PMID:17855619

  5. Distinct Functions of Endophilin Isoforms in Synaptic Vesicle Endocytosis

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    Jifeng Zhang

    2015-01-01

    Full Text Available Endophilin isoforms perform distinct characteristics in their interactions with N-type Ca2+ channels and dynamin. However, precise functional differences for the endophilin isoforms on synaptic vesicle (SV endocytosis remain unknown. By coupling RNA interference and electrophysiological recording techniques in cultured rat hippocampal neurons, we investigated the functional differences of three isoforms of endophilin in SV endocytosis. The results showed that the amplitude of normalized evoked excitatory postsynaptic currents in endophilin1 knockdown neurons decreased significantly for both single train and multiple train stimulations. Similar results were found using endophilin2 knockdown neurons, whereas endophilin3 siRNA exhibited no change compared with control neurons. Endophilin1 and endophilin2 affected SV endocytosis, but the effect of endophilin1 and endophilin2 double knockdown was not different from that of either knockdown alone. This result suggested that endophilin1 and endophilin2 functioned together but not independently during SV endocytosis. Taken together, our results indicate that SV endocytosis is sustained by endophilin1 and endophilin2 isoforms, but not by endophilin3, in primary cultured hippocampal neurons.

  6. Diagnostic accuracy of laser-evoked potentials in diabetic neuropathy.

    Science.gov (United States)

    Di Stefano, Giulia; La Cesa, Silvia; Leone, Caterina; Pepe, Alessia; Galosi, Eleonora; Fiorelli, Marco; Valeriani, Massimiliano; Lacerenza, Marco; Pergolini, Mario; Biasiotta, Antonella; Cruccu, Giorgio; Truini, Andrea

    2017-06-01

    Although the most widely agreed neurophysiological tool for investigating small fiber damage is laser-evoked potential (LEP) recording, no study has documented its diagnostic accuracy. In this clinical, neurophysiological, and skin biopsy study, we collected age-corrected LEP normative ranges, verified the association of LEPs with pinprick sensory disturbances in the typical diabetic mixed fiber polyneuropathy, and assessed the sensitivity and specificity of LEPs in diabetic small fiber neuropathy. From 288 LEP recordings from the face, hand, and foot in 73 healthy subjects, we collected age-corrected normative ranges for LEPs. We then selected 100 patients with mixed-fiber diabetic neuropathy and 25 patients with possible small-fiber diabetic neuropathy. In the 100 patients with mixed fiber neuropathy, we verified how LEP abnormalities were associated with clinically evident pinprick sensory disturbances. In the 25 patients with possible pure small fiber neuropathy, using the skin biopsy for assessing the intraepidermal nerve fiber density as a reference standard, we calculated LEP sensitivity and specificity. In healthy participants, age strongly influenced normative ranges for all LEP variables. By applying age-corrected normative ranges for LEPs, we found that LEPs were strongly associated with pinprick sensory disturbances. In relation to the skin biopsy findings, LEPs yielded 78% sensitivity and 81% specificity in the diagnosis of diabetic small fiber neuropathy. Our study, providing age-corrected normative ranges for the main LEP data and their diagnostic accuracy, helps to make LEPs more reliable as a clinical diagnostic tool, and proposes this technique as a less invasive alternative to skin biopsy for diagnosing diabetic small fiber neuropathy.

  7. EVALUATION OF BRAINSTEM AUDITORY EVOKED POTENTIAL IN MIGRAINE PATIENT

    Directory of Open Access Journals (Sweden)

    Sowmiya R, Vinodha R

    2015-10-01

    Full Text Available Background: Migraine is worldwide common, chronic, Neurovascular disorder, characterized by attacks of severe headache and an Aura involving neurologic symptoms. Its pathogenesis was incompletely understood whether of cortical or brainstem origin. Aim: The present study was undertaken to investigate brainstem auditory functions in Migraine patients. Materials and Methods: The subjects were recruited based on International Headache Society classification for Migraine. Subjects with episodes of headache for at least 2yrs, 2 attacks per month in last quarter year were included in the study. Forty subjects (16 Migraine with Aura & 24 cases – Migraine without aura & forty age / sex matched controls were selected. Brainstem auditory evoked potential was recorded using 4-Channel polygraph (Neuro perfect plus. Electrodes were placed according to 10 – 20 electrode placement system. Auditory stimulus in the form of click sound is delivered through the headphones. Clicks were delivered at a rate of 8-10 /sec. The intensity of the stimulus is set at 30db. About 100 averages were recorded. BAEP waveforms – Wave I, III & V latencies and the interpeak latencies were measured. The results were analysed statistically using student‘t’ test. Results: BAEP recording shows significant prolongation in latencies of Wave I, III & V and the Interpeak latency (IPL I-III, III-V & I-V in Migraine with aura. In Migraine without aura, there was significant prolongation of Wave I, III & V and III-V & I-VIPL (P<0.05. Conclusion: Prolongation suggests that there is involvement of brainstem structures in Migraine, thus BAEP can be used as an effective tool in evaluation of Migraine.

  8. Brainstem auditory-evoked potential in Boxer dogs

    Directory of Open Access Journals (Sweden)

    Mariana Isa Poci Palumbo

    2014-10-01

    Full Text Available Brainstem auditory-evoked potential (BAEP has been widely used for different purposes in veterinary practice and is commonly used to identify inherited deafness and presbycusis. In this study, 43 Boxer dogs were evaluated using the BAEP. Deafness was diagnosed in 3 dogs (2 bilateral and 1 unilateral allowing the remaining 40 Boxers to be included for normative data analysis including an evaluation on the influence of age on the BAEP. The animals were divided into 2 groups of 20 Boxers each based on age. The mean age was 4.54 years (range, 1-8 in group I, and 9.83 years (range, 8.5-12 in group II. The mean latency for I, III, and V waves were 1.14 (±0.07, 2.64 (±0.11, and 3.48 (±0.10 ms in group I, and 1.20 (±0.12, 2.73 (±0.15, and 3.58 (±0.22 ms in group II, respectively. The mean inter-peak latencies for the I-III, III-V and I-V intervals were 1.50 (±0.15, 0.84 (±0.15, and 2.34 (±0.11 ms in group I, and 1.53 (±0.16, 0.85 (±0.15, and 2.38 (±0.19 ms in group II, respectively. Latencies of waves I and III were significant different between group I and II. For the I-III, III-V and I-V intervals, no significant differences were observed between the 2 groups. As far as we know, this is the first normative study of BAEP obtained from Boxer dogs.

  9. Visual Evoked Potential to Assess Retinopathy in Gestational Diabetes Mellitus.

    Science.gov (United States)

    Hari Kumar, K V S; Ahmad, F M H; Sood, Sandeep; Mansingh, Sudhir

    2016-04-01

    We evaluated for early retinopathy using the visual evoked potential (VEP) in patients with gestational diabetes mellitus (GDM) and type 2 diabetes mellitus during pregnancy. All patients with GDM and type 2 diabetes seen between June and October of 2014 were included in this cross-sectional, observational study. Patients with secondary diabetes, ocular or major illness were excluded from the study. VEP was recorded in both eyes to derive prominent positive peak latency (P100), amplitude and initial negative deflection (N75) latency. The data were compared with 10 gestational age-matched controls with normal glucose tolerance. Appropriate statistical methods were used for comparison among the 3 groups. The study participants (40 with GDM, 10 with type 2 diabetes, 10 with normal glucose tolerance) had a median (25th to 75th interquartile range) age of 26 (24.3, 30) years, a gestational age of 24.5 (21, 27) weeks and weights of 66.8 (63.4, 71.5) kg. The P100 latencies were comparable among the 3 groups (p=0.0577). However, patients with any diabetes (GDM and type 2 diabetes) had prolonged P100 latencies (p=0.0139) and low P100 amplitudes (p=0.0391) in comparison to controls. P100 latency showed a direct correlation with hyperglycemia (p=0.0118). Our data showed that VEP abnormalities are detectable even in the short-term hyperglycemia of GDM and type 2 diabetes. Copyright © 2016 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

  10. Early and late activity in somatosensory cortex reflects changes in bodily self-consciousness: an evoked potential study.

    Science.gov (United States)

    Aspell, J E; Palluel, E; Blanke, O

    2012-08-02

    How can we investigate the brain mechanisms underlying self-consciousness? Recent behavioural studies on multisensory bodily perception have shown that multisensory conflicts can alter bodily self-consciousness such as in the "full body illusion" (FBI) in which changes in self-identification with a virtual body and tactile perception are induced. Here we investigated whether experimental changes in self-identification during the FBI are accompanied by activity changes in somatosensory cortex by recording somatosensory-evoked potentials (SEPs). To modulate self-identification, participants were filmed by a video camera from behind while their backs were stroked, either synchronously (illusion condition) or asynchronously (control condition) with respect to the stroking seen on their virtual body. Tibial nerve SEPs were recorded during the FBI and analysed using evoked potential (EP) mapping. Tactile mislocalisation was measured using the crossmodal congruency task. SEP mapping revealed five sequential periods of brain activation during the FBI, of which two differed between the illusion condition and the control condition. Activation at 30-50 ms (corresponding to the P40 component) in primary somatosensory cortex was stronger in the illusion condition. A later activation at ∼110-200 ms, likely originating in higher-tier somatosensory regions in parietal cortex, was stronger and lasted longer in the control condition. These data show that changes in bodily self-consciousness modulate activity in primary and higher-tier somatosensory cortex at two distinct processing steps. We argue that early modulations of primary somatosensory cortex may be a consequence of (1) multisensory integration of synchronous vs. asynchronous visuo-tactile stimuli and/or (2) differences in spatial attention (to near or far space) between the conditions. The later activation in higher-tier parietal cortex (and potentially other regions in temporo-parietal and frontal cortex) likely

  11. Acute stress evokes sexually dimorphic, stressor-specific patterns of neural activation across multiple limbic brain regions in adult rats.

    Science.gov (United States)

    Sood, Ankit; Chaudhari, Karina; Vaidya, Vidita A

    2018-03-01

    Stress enhances the risk for psychiatric disorders such as anxiety and depression. Stress responses vary across sex and may underlie the heightened vulnerability to psychopathology in females. Here, we examined the influence of acute immobilization stress (AIS) and a two-day short-term forced swim stress (FS) on neural activation in multiple cortical and subcortical brain regions, implicated as targets of stress and in the regulation of neuroendocrine stress responses, in male and female rats using Fos as a neural activity marker. AIS evoked a sex-dependent pattern of neural activation within the cingulate and infralimbic subdivisions of the medial prefrontal cortex (mPFC), lateral septum (LS), habenula, and hippocampal subfields. The degree of neural activation in the mPFC, LS, and habenula was higher in males. Female rats exhibited reduced Fos positive cell numbers in the dentate gyrus hippocampal subfield, an effect not observed in males. We addressed whether the sexually dimorphic neural activation pattern noted following AIS was also observed with the short-term stress of FS. In the paraventricular nucleus of the hypothalamus and the amygdala, FS similar to AIS resulted in robust increases in neural activation in both sexes. The pattern of neural activation evoked by FS was distinct across sexes, with a heightened neural activation noted in the prelimbic mPFC subdivision and hippocampal subfields in females and differed from the pattern noted with AIS. This indicates that the sex differences in neural activation patterns observed within stress-responsive brain regions are dependent on the nature of stressor experience.

  12. Pure phase-locking of beta/gamma oscillation contributes to the N30 frontal component of somatosensory evoked potentials

    Directory of Open Access Journals (Sweden)

    Leroy Axelle

    2007-09-01

    Full Text Available Abstract Background Evoked potentials have been proposed to result from phase-locking of electroencephalographic (EEG activities within specific frequency bands. However, the respective contribution of phasic activity and phase resetting of ongoing EEG oscillation remains largely debated. We here applied the EEGlab procedure in order to quantify the contribution of electroencephalographic oscillation in the generation of the frontal N30 component of the somatosensory evoked potentials (SEP triggered by median nerve electrical stimulation at the wrist. Power spectrum and intertrial coherence analysis were performed on EEG recordings in relation to median nerve stimulation. Results The frontal N30 component was accompanied by a significant phase-locking of beta/gamma oscillation (25–35 Hz and to a lesser extent of 80 Hz oscillation. After the selection in each subject of the trials for which the power spectrum amplitude remained unchanged, we found pure phase-locking of beta/gamma oscillation (25–35 Hz peaking about 30 ms after the stimulation. Transition across trials from uniform to normal phase distribution revealed temporal phase reorganization of ongoing 30 Hz EEG oscillations in relation to stimulation. In a proportion of trials, this phase-locking was accompanied by a spectral power increase peaking in the 30 Hz frequency band. This corresponds to the complex situation of 'phase-locking with enhancement' in which the distinction between the contribution of phasic neural event versus EEG phase resetting is hazardous. Conclusion The identification of a pure phase-locking in a large proportion of the SEP trials reinforces the contribution of the oscillatory model for the physiological correlates of the frontal N30. This may imply that ongoing EEG rhythms, such as beta/gamma oscillation, are involved in somatosensory information processing.

  13. Concurrent Isolation of 3 Distinct Cardiac Stem Cell Populations From a Single Human Heart Biopsy.

    Science.gov (United States)

    Monsanto, Megan M; White, Kevin S; Kim, Taeyong; Wang, Bingyan J; Fisher, Kristina; Ilves, Kelli; Khalafalla, Farid G; Casillas, Alexandria; Broughton, Kathleen; Mohsin, Sadia; Dembitsky, Walter P; Sussman, Mark A

    2017-07-07

    The relative actions and synergism between distinct myocardial-derived stem cell populations remain obscure. Ongoing debates on optimal cell population(s) for treatment of heart failure prompted implementation of a protocol for isolation of multiple stem cell populations from a single myocardial tissue sample to develop new insights for achieving myocardial regeneration. Establish a robust cardiac stem cell isolation and culture protocol to consistently generate 3 distinct stem cell populations from a single human heart biopsy. Isolation of 3 endogenous cardiac stem cell populations was performed from human heart samples routinely discarded during implantation of a left ventricular assist device. Tissue explants were mechanically minced into 1 mm3 pieces to minimize time exposure to collagenase digestion and preserve cell viability. Centrifugation removes large cardiomyocytes and tissue debris producing a single cell suspension that is sorted using magnetic-activated cell sorting technology. Initial sorting is based on tyrosine-protein kinase Kit (c-Kit) expression that enriches for 2 c-Kit+ cell populations yielding a mixture of cardiac progenitor cells and endothelial progenitor cells. Flowthrough c-Kit- mesenchymal stem cells are positively selected by surface expression of markers CD90 and CD105. After 1 week of culture, the c-Kit+ population is further enriched by selection for a CD133+ endothelial progenitor cell population. Persistence of respective cell surface markers in vitro is confirmed both by flow cytometry and immunocytochemistry. Three distinct cardiac cell populations with individualized phenotypic properties consistent with cardiac progenitor cells, endothelial progenitor cells, and mesenchymal stem cells can be successfully concurrently isolated and expanded from a single tissue sample derived from human heart failure patients. © 2017 American Heart Association, Inc.

  14. Biologically distinct subsets of nevi

    Science.gov (United States)

    ROGERS, Tova; MARINO, Maria L.; RACITI, Patricia; JAIN, Manu; BUSAM, Klaus J.; MARCHETTI, Michael A.; MARGHOOB, Ashfaq A.

    2017-01-01

    Melanocytic nevi (MN) encompass a range of benign tumors with varying microscopic and macroscopic features. Their development is a multifactorial process under genetic and environmental influences. The clinical importance of MN lies in distinguishing them from melanoma and in recognizing their associations with melanoma risk and cancer syndromes. Historically, the distinction between the different types of MN, as well as between MN and melanoma, was based on clinical history, gross morphology, and histopathological features. While histopathology with clinical correlation remains the gold standard for differentiating and diagnosing melanocytic lesions, in some cases, this may not be possible. The use of dermoscopy has allowed for the assessment of subsurface skin structures and has contributed to the clinical evaluation and classification of MN. Genetic profiling, while still in its early stages, has the greatest potential to refine the classification of MN by clarifying their developmental processes, biological behaviors, and relationships to melanoma. Here we review the most salient clinical, dermoscopic, histopathological, and genetic features of different MN subgroups. PMID:27119653

  15. Penoscrotal porokeratosis: A distinct entity

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    Rajiv Joshi

    2015-01-01

    Full Text Available A 26-year-old man presented with five months history of redness associated with itching and burning over the scrotum and shaft of the penis with a persistent rash on those sites. There had been no response to topical steroid and antifungal creams. Clinical examination revealed a large well-circumscribed erythematous plaque with a thready raised border with a tiny groove at its summit that involved almost two-thirds of the ventral part of the shaft of the penis. Ill-defined erythema with a granular surface was seen over the anterior scrotal skin. A 4 mm punch biopsy of the plaque on the penile shaft revealed multiple cornoid lamellae located adjacent to one another. The patient was treated with topical emollients. Follow up after four months revealed almost complete resolution of the plaque on the penile shaft. Penoscrotal porokeratosis appears to be a distinct entity in the family of porokeratotic diseases, described only in young males in their twenties with involvement of the penile shaft and anterior scrotum with severe burning and itching and histologically associated with multiple cornoid lamellae. It may represent an unusual epidermal porokeratotic reaction pattern and may be a self-resolving condition.

  16. Fifty shades of blue : classification of music-evoked sadness.

    OpenAIRE

    Peltola, Henna-Riikka; Eerola, Tuomas

    2016-01-01

    It has been repeatedly shown that sad music induces mainly pleasant or mixed emotions, and is particularly relevant for self-regulation goals. However, this is not entirely compatible with the view that sadness is one of the basic emotions experienced in the face of an unpleasant event or a loss. Also, a distinction between grief and sadness is often drawn, which seemingly does not have relevance in relation to musical experiences. The discrepancy between the positive accounts of emotions ass...

  17. Quantifying interhemispheric symmetry of somatosensory evoked potentials with the intraclass correlation coefficient

    NARCIS (Netherlands)

    van de Wassenberg, Wilma J. G.; van der Hoeven, Johannes H.; Leenders, Klaus L.; Maurits, Natasha M.

    Although large intersubject variability is reported for cortical somatosensory evoked potentials (SEPs), variability between hemispheres within one subject is thought to be small. Therefore, interhemispheric comparison of SEP waveforms might be clinically useful to detect unilateral abnormalities in

  18. Prestimulus amplitudes modulate P1 latencies and evoked traveling alpha waves

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    Nicole Alexandra Himmelstoss

    2015-05-01

    Full Text Available Traveling waves have been well documented in the ongoing, and more recently also in the evoked EEG. In the present study we investigate what kind of physiological process might be responsible for inducing an evoked traveling wave. We used a semantic judgment task which already proved useful to study evoked traveling alpha waves that coincide with the appearance of the P1 component. We found that the P1 latency of the leading electrode is significantly correlated with prestimulus amplitude size and that this event is associated with a transient change in alpha frequency. We assume that cortical background excitability, as reflected by an increase in prestimulus amplitude, is responsible for the observed change in alpha frequency and the initiation of an evoked traveling trajectory.

  19. The Role of Odor-Evoked Memory in Psychological and Physiological Health

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    Rachel S. Herz

    2016-07-01

    Full Text Available This article discusses the special features of odor-evoked memory and the current state-of-the-art in odor-evoked memory research to show how these unique experiences may be able to influence and benefit psychological and physiological health. A review of the literature leads to the conclusion that odors that evoke positive autobiographical memories have the potential to increase positive emotions, decrease negative mood states, disrupt cravings, and reduce physiological indices of stress, including systemic markers of inflammation. Olfactory perception factors and individual difference characteristics that would need to be considered in therapeutic applications of odor-evoked-memory are also discussed. This article illustrates how through the experimentally validated mechanisms of odor-associative learning and the privileged neuroanatomical relationship that exists between olfaction and the neural substrates of emotion, odors can be harnessed to induce emotional and physiological responses that can improve human health and wellbeing.

  20. Assessment evaluation of transient evoked otoacoustic emission by contralateral suppression in tinnitus patient with normal hearing

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    Helnaz Mokrian

    2014-01-01

    Conclusion: The suppression of the transient evoked otoacoustic emission by contralateral white noise did not reach statistically significant levels in tinnitus patients while the amplitude in control group reduced significantly.

  1. Dynamic Lateralization of Pupil Dilation Evoked by Locus Coeruleus Activation Results from Sympathetic, Not Parasympathetic, Contributions

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    Yang Liu

    2017-09-01

    Full Text Available Pupil size is collectively controlled by the sympathetic dilator and parasympathetic sphincter muscles. Locus coeruleus (LC activation has been shown to evoke pupil dilation, but how the sympathetic and parasympathetic pathways contribute to this dilation remains unknown. We examined pupil dilation elicited by LC activation in lightly anesthetized rats. Unilateral LC activation evoked bilateral but lateralized pupil dilation; i.e., the ipsilateral dilation was significantly larger than the contralateral dilation. Surgically blocking the ipsilateral, but not contralateral, sympathetic pathway significantly reduced lateralization, suggesting that lateralization is mainly due to sympathetic contribution. Moreover, we found that sympathetic, but not parasympathetic, contribution is correlated with LC activation frequency. Together, our results unveil the frequency-dependent contributions of the sympathetic and parasympathetic pathways to LC activation-evoked pupil dilation and suggest that lateralization in task-evoked pupil dilations may be used as a biomarker for autonomic tone.

  2. Clinical Evaluation of the Vestibular Nerve Using Vestibular Evoked Myogenic Potentials.

    Science.gov (United States)

    Bogle, Jamie M

    2018-01-01

    Vestibular evoked myogenic potentials are currently the most clinically accessible method to evaluate the otolith reflex pathways. These responses provide unique information regarding the status of the utriculo-ocular and sacculo-collic reflex pathways, information that has previously been unavailable. Vestibular evoked myogenic potentials are recorded from tonically contracted target muscles known to be innervated by these respective otolith organs. Diagnosticians can use vestibular evoked myogenic potentials to better evaluate the overall integrity of the inner ear and neural pathways; however, there are specific considerations for each otolith reflex protocol. In addition, specific patient populations may require protocol variations to better evaluate atypical function of the inner ear organs, vestibular nerve transmission, or subsequent reflex pathways. This is a review of the clinical application and interpretation of cervical and ocular vestibular evoked myogenic potentials.

  3. Music‐evoked emotions: principles, brain correlates, and implications for therapy

    National Research Council Canada - National Science Library

    Koelsch, Stefan

    2015-01-01

    ... to provide a starting point for a systematic, coherent, and comprehensive theory on music‐evoked emotions that considers both reception and production of music, as well as the relevance of emotion...

  4. Conditioning stimulation techniques for enhancement of transcranially elicited evoked motor responses

    NARCIS (Netherlands)

    Journee, H. -L.; Polak, H. E.; De Kleuver, M.

    2007-01-01

    Introduction. - In spite of the use of multipulse, transcranial electrical stimulation (TES) is still insufficient in a subgroup of patients to elicit motor-evoked potentials during intraoperative neurophysiological monitoring (IONM). Classic facilitation methods used in awake patients are precluded

  5. Heat shock protein 70, heat shock protein 32, and vascular endothelial growth factor production and their effects on lipopolysaccharide-induced apoptosis in porcine aortic endothelial cells.

    Science.gov (United States)

    Bernardini, Chiara; Zannoni, Augusta; Turba, Maria Elena; Fantinati, Paolo; Tamanini, Carlo; Bacci, Maria Laura; Forni, Monica

    2005-01-01

    Lipopolysaccharide (LPS) is a highly proactive molecule that causes in vivo a systemic inflammatory response syndrome and activates in vitro the inflammatory pathway in different cellular types, including endothelial cells (EC). Because the proinflammatory status could lead to EC injury and apoptosis, the expression of proinflammatory genes must be finely regulated through the induction of protective genes. This study aimed at determining whether an LPS exposure is effective in inducing apoptosis in primary cultures of porcine aortic endothelial cells and in stimulating heat shock protein (Hsp)70 and Hsp32 production as well as vascular endothelial growth factor (VEGF) secretion. Cells between third and eighth passage were exposed to 10 microg/mL LPS for 1, 7, 15, and 24 hours (time-course experiments) or to 1, 10, and 100 microg/mL LPS for 7 and 15 hours (dose-response experiments). Apoptosis was not affected by 1 microg/mL LPS but significantly increased in a dose-dependent manner with the highest LPS doses. Furthermore, apoptosis rate increased only till 15 hours of LPS exposure. LPS stimulated VEGF secretion in a dose-dependent manner; its effect became significant after 7 hours and reached a plateau after 15 hours. Both Hsp70 and Hsp32 expressions were induced by LPS in a dose-dependent manner after 7 hours. Subsequent studies were addressed to evaluate the protective role of Hsp32, Hsp70, and VEGF. Hemin, an Hsp32 inducer (5, 20, 50 microM), and recombinant VEGF (100 and 200 ng/mL), were added to the culture 2 hours before LPS (10 microg/mL for 24 hours); to induce Hsp70 expression, cells were heat shocked (42 degrees C for 1 hour) 15 hours before LPS (10 microg/mL for 24 hours). Hemin exposure upregulated Hsp32 expression in a dose-dependent manner and protected cells against LPS-induced apoptosis. Heat shock (HS) stimulated Hsp70 expression but failed to reduce LPS-induced apoptosis; VEGF addition did not protect cells against LPS-induced apoptosis at any

  6. Characterisation of Weibel-Palade body fusion by amperometry in endothelial cells reveals fusion pore dynamics and the effect of cholesterol on exocytosis.

    Science.gov (United States)

    Cookson, Emma A; Conte, Ianina L; Dempster, John; Hannah, Matthew J; Carter, Tom

    2013-12-01

    Regulated secretion from endothelial cells is mediated by Weibel-Palade body (WPB) exocytosis. Plasma membrane cholesterol is implicated in regulating secretory granule exocytosis and fusion pore dynamics; however, its role in modulating WPB exocytosis is not clear. To address this we combined high-resolution electrochemical analysis of WPB fusion pore dynamics, by amperometry, with high-speed optical imaging of WPB exocytosis following cholesterol depletion or supplementation in human umbilical vein endothelial cells. We identified serotonin (5-HT) immunoreactivity in WPBs, and VMAT1 expression allowing detection of secreted 5-HT as discrete current spikes during exocytosis. A high proportion of spikes (∼75%) had pre-spike foot signals, indicating that WPB fusion proceeds via an initial narrow pore. Cholesterol depletion significantly reduced pre-spike foot signal duration and increased the rate of fusion pore expansion, whereas cholesterol supplementation had broadly the reverse effect. Cholesterol depletion slowed the onset of hormone-evoked WPB exocytosis, whereas its supplementation increased the rate of WPB exocytosis and hormone-evoked proregion secretion. Our results provide the first analysis of WPB fusion pore dynamics and highlight an important role for cholesterol in the regulation of WPB exocytosis.

  7. Cervical intraspinal microstimulation evokes robust forelimb movements before and after injury

    Science.gov (United States)

    Sunshine, Michael D.; Cho, Frances S.; Lockwood, Danielle R.; Fechko, Amber S.; Kasten, Michael R.; Moritz, Chet T.

    2013-06-01

    Objective. Intraspinal microstimulation (ISMS) is a promising method for reanimating paralyzed limbs following neurological injury. ISMS within the cervical and lumbar spinal cord is capable of evoking a variety of highly-functional movements prior to injury, but the ability of ISMS to evoke forelimb movements after cervical spinal cord injury is unknown. Here we examine the forelimb movements and muscles activated by cervical ISMS both before and after contusion injury. Approach. We documented the forelimb muscles activated and movements evoked via systematic stimulation of the rodent cervical spinal cord both before injury and three, six and nine weeks following a moderate C4/C5 lateralized contusion injury. Animals were anesthetized with isoflurane to permit construction of somatotopic maps of evoked movements and quantify evoked muscle synergies between cervical segments C3 and T1. Main results. When ISMS was delivered to the cervical spinal cord, a variety of responses were observed at 68% of locations tested, with a spatial distribution that generally corresponded to the location of motor neuron pools. Stimulus currents required to achieve movement and the number of sites where movements could be evoked were unchanged by spinal cord injury. A transient shift toward extension-dominated movements and restricted muscle synergies were observed at three and six weeks following injury, respectively. By nine weeks after injury, however, ISMS-evoked patterns were similar to spinally-intact animals. Significance. The results demonstrate the potential for cervical ISMS to reanimate hand and arm function following spinal cord injury. Robust forelimb movements can be evoked both before and during the chronic stages of recovery from a clinically relevant and sustained cervical contusion injury.

  8. Visual evoked potentials in Negro carriers of the gene for tyrosinase positive oculocutaneous albinism.

    Science.gov (United States)

    Castle, D; Kromberg, J; Kowalsky, R; Moosa, R; Gillman, N; Zwane, E; Fritz, V

    1988-01-01

    Visual evoked potential testing was performed on 15 Negro carriers of the gene for tyrosinase positive oculocutaneous albinism in order to detect whether they have the same visual pathway decussation anomalies as do homozygotes. No subject showed 01-02 asymmetry on monocular testing, indicating that decussation follows the normal pattern. It is concluded that visual evoked potential testing is probably not useful in the detection of Negroes heterozygous for the gene for tyrosinase positive oculocutaneous albinism. PMID:3148727

  9. The paradox of music-evoked sadness:an online survey

    OpenAIRE

    Liila Taruffi; Stefan Koelsch

    2014-01-01

    This study explores listeners’ experience of music-evoked sadness. Sadness is typically assumed to be undesirable and is therefore usually avoided in everyday life. Yet the question remains: Why do people seek and appreciate sadness in music? We present findings from an online survey with both Western and Eastern participants (N = 772). The survey investigates the rewarding aspects of music-evoked sadness, as well as the relative contribution of listener characteristics and situational factor...

  10. Skinfold thickness affects the isometric knee extension torque evoked by Neuromuscular Electrical Stimulation

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    Flávia V. A. Medeiros

    2015-12-01

    Full Text Available BACKGROUND: Subcutaneous adipose tissue may influence the transmission of electrical stimuli through to the skin, thus affecting both evoked torque and comfort perception associated with neuromuscular electrical stimulation (NMES. This could seriously affect the effectiveness of NMES for either rehabilitation or sports purposes. OBJECTIVE: To investigate the effects of skinfold thickness (SFT on maximal NMES current intensity, NMES-evoked torque, and NMES-induced discomfort. METHOD: First, we compared NMES current intensity, NMES-induced discomfort, and NMES-evoked torque between two subgroups of subjects with thicker (n=10; 20.7 mm vs. thinner (n=10; 29.4 mm SFT. Second, we correlated SFT to NMES current intensity, NMES-induced discomfort, and NMES-evoked knee extension torque in 20 healthy women. The NMES-evoked torque was normalized to the maximal voluntary contraction (MVC torque. The discomfort induced by NMES was assessed with a visual analog scale (VAS. RESULTS: NMES-evoked torque was 27.5% lower in subjects with thicker SFT (p=0.01 while maximal current intensity was 24.2% lower in subjects with thinner SFT (p=0.01. A positive correlation was found between current intensity and SFT (r=0.540, p=0.017. A negative correlation was found between NMES-evoked torque and SFT (r=-0.563, p=0.012. No significant correlation was observed between discomfort scores and SFT (rs=0.15, p=0.53. CONCLUSION: These results suggest that the amount of subcutaneous adipose tissue (as reflected by skinfold thickness affected NMES current intensity and NMES-evoked torque, but had no effect on discomfort perception. Our findings may help physical therapists to better understand the impact of SFT on NMES and to design more rational stimulation strategies.

  11. Transient evoked otoacoustic emissions testing for screening of sensorineural deafness in puppies

    OpenAIRE

    McBrearty, A; Penderis, J

    2011-01-01

    Background: Transient evoked otoacoustic emissions (TEOAE) are widely used for human neonatal deafness screening, but have not been reported for clinical use in dogs. \\ud \\ud Hypothesis/Objectives: To investigate the feasibility of TEOAE testing in conscious puppies and the ability of TEOAE testing to correctly identify deaf and hearing ears, as defined by brainstem auditory evoked response (BAER). \\ud \\ud Animals: Forty puppies from 10 litters. \\ud \\ud Methods: Prospective study on puppies p...

  12. Effect of eye lateralization on contralateral suppression of transient evoked otoacoustic emissions

    OpenAIRE

    SOI, D.; Brambilla, D; COMIOTTO, E.; DI Berardino, F; Filipponi, E.; Socci, M; SPREAFICO, E.; Forti, S.; CESARANI, A.

    2012-01-01

    SUMMARY Several studies have previously demonstrated that postural changes modify evoked otoacoustic emission. In order to evaluate a possible interaction between eye muscles and ciliated cells in the inner ear, we studied the effects of eye lateralization on the contralateral suppression of transient evoked otoacoustic emissions (TEOAEs). Thirty-eight normal hearing subjects with TEOAEs were recruited. Their TEAOEs at threshold level were recorded with contralateral suppression (white noise)...

  13. Awareness during anaesthesia for surgery requiring evoked potential monitoring: A pilot study

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    Pritish J Korula

    2017-01-01

    Full Text Available Background: Evoked potential monitoring such as somatosensory-evoked potential (SSEP or motor-evoked potential (MEP monitoring during surgical procedures in proximity to the spinal cord requires minimising the minimum alveolar concentrations (MACs below the anaesthetic concentrations normally required (1 MAC to prevent interference in amplitude and latency of evoked potentials. This could result in awareness. Our primary objective was to determine the incidence of awareness while administering low MAC inhalational anaesthetics for these unique procedures. The secondary objective was to assess the adequacy of our anaesthetic technique from neurophysiologist′s perspective. Methods: In this prospective observational pilot study, 61 American Society of Anesthesiologists 1 and 2 patients undergoing spinal surgery for whom intraoperative evoked potential monitoring was performed were included; during the maintenance phase, 0.7-0.8 MAC of isoflurane was targeted. We evaluated the intraoperative depth of anaesthesia using a bispectral (BIS index monitor as well as the patients response to surgical stimulus (PRST scoring system. Post-operatively, a modified Bruce questionnaire was used to verify awareness. The adequacy of evoked potential readings was also assessed. Results: Of the 61 patients, no patient had explicit awareness. Intraoperatively, 19 of 61 patients had a BIS value of above sixty at least once, during surgery. There was no correlation with PRST scoring and BIS during surgery. Fifty-four out of 61 patient′s evoked potential readings were deemed ′good′ or ′fair′ for the conduct of electrophysiological monitoring. Conclusions: This pilot study demonstrates that administering low MAC inhalational anaesthetics to facilitate evoked potential monitoring does not result in explicit awareness. However, larger studies are needed to verify this. The conduct of SSEP electrophysiological monitoring was satisfactory with the use of this

  14. Neuromodulation of evoked muscle potentials induced by epidural spinal-cord stimulation in paralyzed individuals.

    Science.gov (United States)

    Sayenko, Dimitry G; Angeli, Claudia; Harkema, Susan J; Edgerton, V Reggie; Gerasimenko, Yury P

    2014-03-01

    Epidural stimulation (ES) of the lumbosacral spinal cord has been used to facilitate standing and voluntary movement after clinically motor-complete spinal-cord injury. It seems of importance to examine how the epidurally evoked potentials are modulated in the spinal circuitry and projected to various motor pools. We hypothesized that chronically implanted electrode arrays over the lumbosacral spinal cord can be used to assess functionally spinal circuitry linked to specific motor pools. The purpose of this study was to investigate the functional and topographic organization of compound evoked potentials induced by the stimulation. Three individuals with complete motor paralysis of the lower limbs participated in the study. The evoked potentials to epidural spinal stimulation were investigated after surgery in a supine position and in one participant, during both supine and standing, with body weight load of 60%. The stimulation was delivered with intensity from 0.5 to 10 V at a frequency of 2 Hz. Recruitment curves of evoked potentials in knee and ankle muscles were collected at three localized and two wide-field stimulation configurations. Epidural electrical stimulation of rostral and caudal areas of lumbar spinal cord resulted in a selective topographical recruitment of proximal and distal leg muscles, as revealed by both magnitude and thresholds of the evoked potentials. ES activated both afferent and efferent pathways. The components of neural pathways that can mediate motor-evoked potentials were highly dependent on the stimulation parameters and sensory conditions, suggesting a weight-bearing-induced reorganization of the spinal circuitries.

  15. Characterization of Motor and Somatosensory Evoked Potentials in the Yucatan Micropig Using Transcranial and Epidural Stimulation.

    Science.gov (United States)

    Benavides, Francisco D; Santamaria, Andrea J; Bodoukhin, Nikita; Guada, Luis G; Solano, Juan P; Guest, James D

    2017-09-15

    Yucatan micropigs have brain and spinal cord dimensions similar to humans and are useful for certain spinal cord injury (SCI) translational studies. Micropigs are readily trained in behavioral tasks, allowing consistent testing of locomotor loss and recovery. However, there has been little description of their motor and sensory pathway neurophysiology. We established methods to assess motor and sensory cortical evoked potentials in the anesthetized, uninjured state. We also evaluated epidurally evoked motor and sensory stimuli from the T6 and T9 levels, spanning the intended contusion injury epicenter. Response detection frequency, mean latency and amplitude values, and variability of evoked potentials were determined. Somatosensory evoked potentials were reliable and best detected during stimulation of peripheral nerve and epidural stimulation by referencing the lateral cortex to midline Fz. The most reliable hindlimb motor evoked potential (MEP) occurred in tibialis anterior. We found MEPs in forelimb muscles in response to thoracic epidural stimulation likely generated from propriospinal pathways. Cranially stimulated MEPs were easier to evoke in the upper limbs than in the hindlimbs. Autopsy studies revealed substantial variations in cortical morphology between animals. This electrophysiological study establishes that neurophysiological measures can be reliably obtained in micropigs in a time frame compatible with other experimental procedures, such as SCI and transplantation. It underscores the need to better understand the motor control pathways, including the corticospinal tract, to determine which therapeutics are suitable for testing in the pig model.

  16. Distinctiveness of Ugandapithecus from Proconsul

    Directory of Open Access Journals (Sweden)

    Gommery, D.

    2009-12-01

    Full Text Available The decision to create the genus Ugandapithecus by Senut et al., 2000 has been criticised, either directly and in detail by MacLatchy & Rossie (2005b who argued that it is a junior synonym of Proconsul, or indirectly without providing reasons, firstly by Harrison (2001 who wrote that he did not retain it as a genus distinct from Proconsul, and then by Suwa et al., (2007 who employed the name “Ugandapithecus” with inverted commas, implying some degree of doubt about its validity as a genus, but without providing details. More recently Harrison & Andrews (2009 have recognised the Meswa sample as a separate species but they argue that it should be maintained within Proconsul, despite the morphological differences that it has from other species of the genus. We here re-examine the question by comparing, on the one hand, the holotype maxilla of Proconsul africanus, the type species of the genus, with the upper dentition of Ugandapithecus major, and, on the other hand, the holotype mandible of Ugandapithecus major with the lower dentition and mandibles previously attributed to Proconsul africanus. We conclude that the differences between the known upper and lower dentitions of P. africanus and U. major are of such a degree that the two taxa warrant generic separation, and that the differences are not related to sexual dimorphism. Where Proconsul africanus differs from Ugandapithecus major, it approaches Proconsul nyanzae and Proconsul heseloni from Rusinga.Furthermore, the range of morphometric variation within the fossil samples previously attributed to Ugandapithecus major is so great that it far surpasses variation in any other hominoid, fossil or extant. Previously this great amount of variation was interpreted to mean that U. major was extremely dimorphic, with huge males and small females, but if this is true, then U. major would be unique among hominoids in having females in which the cheek teeth fall completely outside the range of

  17. Umbilical Cord Blood Circulating Progenitor Cells and Endothelial Colony-Forming Cells Are Decreased in Preeclampsia.

    Science.gov (United States)

    Gumina, Diane L; Black, Claudine P; Balasubramaniam, Vivek; Winn, Virginia D; Baker, Christopher D

    2017-07-01

    Preeclampsia (PE) is a pregnancy-specific disease characterized by the new onset of hypertension and proteinuria. Mothers with PE are known to develop endothelial dysfunction, but its effect on infants has been understudied, as newborns are often asymptomatic. Recent studies indicate that infants born from preeclamptic pregnancies develop endothelial dysfunction including higher blood pressure during childhood and an increased risk of stroke later in life. We hypothesize that PE reduces the number and function of fetal angiogenic progenitor cells and may contribute to this increased risk. We quantified 2 distinct types of angiogenic progenitors, pro-angiogenic circulating progenitor cells (CPCs) and endothelial colony-forming cells (ECFCs), from the umbilical cord blood of preeclamptic pregnancies and normotensive controls. Pro-angiogenic and nonangiogenic CPCs were enumerated via flow cytometry and ECFCs by cell culture. Additionally, we studied the growth, migration, and tube formation of ECFCs from PE and gestational age-matched normotensive control pregnancies. We found that PE resulted in decreased cord blood pro-angiogenic CPCs and ECFCs. Nonangiogenic CPCs were also decreased. Preeclamptic ECFCs demonstrated decreased growth and migration but formed tube-like structures in vitro similar to controls. Our results suggest that the preeclamptic environment alters the number and function of angiogenic progenitor cells and may increase the risk of later vascular disease.

  18. Griffonia simplicifolia lectins bind specifically to endothelial cells and some epithelial cells in mouse tissues.

    Science.gov (United States)

    Laitinen, L

    1987-04-01

    The binding of Griffonia simplicifolia agglutinin-I (GSA-I) and the isolectins GSA-I-AB3 and GSA-I-B4, having affinity for some alpha-D-galactosyl and N-acetyl galactosaminyl residues was studied in different mouse tissues. In brain, cardiac muscle and skeletal muscle, the GSA-I-lectin conjugates showed prominent binding only to blood vessel endothelia. Similarly, in the liver and kidney cortex the GSA-I-conjugates selectively reacted with endothelial cells of the sinusoids and with intertubular and glomerular capillaries, respectively. However, a strong reactivity with the GSA-I-conjugates was additionally seen in the acinar cells of the pancreas, in the stratified squamous epithelia of skin and tongue, and in transitional epithelium. SDS-PAGE electrophoresis combined with the lectin-blotting technique indicated that a similar set of glycoproteins are responsible for the GSA-I binding, even in different tissues. Another lectin with specificity for alpha-D-galactose, the Maclura pomifera agglutinin, displayed a distinctly different distribution of binding sites, mainly in the basement membranes, of all mouse tissues studied. The results suggest that some alpha-D-galactosyl residues, recognized by the binding of GSA-I lectins, are preferentially expressed in endothelial cells of mouse tissues, and also provide further evidence that endothelial cells can present a highly specific surface glycosylation pattern.

  19. Leukocyte- and endothelial-derived microparticles: a circulating source for fibrinolysis

    Science.gov (United States)

    Lacroix, Romaric; Plawinski, Laurent; Robert, Stéphane; Doeuvre, Loïc; Sabatier, Florence; Martinez de Lizarrondo, Sara; Mezzapesa, Anna; Anfosso, Francine; Leroyer, Aurelie S.; Poullin, Pascale; Jourde, Noémie; Njock, Makon-Sébastien; Boulanger, Chantal M.; Anglés-Cano, Eduardo; Dignat-George, Françoise

    2012-01-01

    Background We recently assigned a new fibrinolytic function to cell-derived microparticles in vitro. In this study we explored the relevance of this novel property of microparticles to the in vivo situation. Design and Methods Circulating microparticles were isolated from the plasma of patients with thrombotic thrombocytopenic purpura or cardiovascular disease and from healthy subjects. Microparticles were also obtained from purified human blood cell subpopulations. The plasminogen activators on microparticles were identified by flow cytometry and enzyme-linked immunosorbent assays; their capacity to generate plasmin was quantified with a chromogenic assay and their fibrinolytic activity was determined by zymography. Results Circulating microparticles isolated from patients generate a range of plasmin activity at their surface. This property was related to a variable content of urokinase-type plasminogen activator and/or tissue plasminogen activator. Using distinct microparticle subpopulations, we demonstrated that plasmin is generated on endothelial and leukocyte microparticles, but not on microparticles of platelet or erythrocyte origin. Leukocyte-derived microparticles bear urokinase-type plasminogen activator and its receptor whereas endothelial microparticles carry tissue plasminogen activator and tissue plasminogen activator/inhibitor complexes. Conclusions Endothelial and leukocyte microparticles, bearing respectively tissue plasminogen activator or urokinase-type plasminogen activator, support a part of the fibrinolytic activity in the circulation which is modulated in pathological settings. Awareness of this blood-borne fibrinolytic activity conveyed by microparticles provides a more comprehensive view of the role of microparticles in the hemostatic equilibrium. PMID:22733025

  20. PV-1 expression could distinguish the subset of caveolae-presenting telocytes that are endothelial progenitors.

    Science.gov (United States)

    Vrapciu, Alexandra Diana; Rusu, Mugurel Constantin

    2017-01-01

    Telocytes (TCs) are stromal cells with characteristic long, thin and moniliform prolongations termed telopodes. They were formerly termed interstitial Cajal-like cells. A characteristic set of markers to identify TCs in light microscopy has not been established until now. Transmission electron microscopy (TEM) is a better tool for identifying TCs. Telocytes display caveolae and can express caveolin-1. On the other hand, endothelial cells (ECs) as well as endothelial progenitor cells (EPCs) have caveolae. Recent evidence suggests that a subset of TCs are in fact EPCs. The distinction of this progenitor subset of TCs can be easily made by a specific set of ultrastructure markers, as follows. Caveolae of endothelial cells present stomatal diaphragms (SDs). The plasmalemma vesicle-associated protein-1 (PV-1), which is identical with the Pathologische Anatomie Leiden endothelium (PAL-E), is specifically identifying the ECs SDs of caveolae. We therefore raise the reasonable hypothesis that the EPCs subset of caveolae-presenting TCs could be accurately identified, without exploration in TEM, by the positive expression of PV-1 or PAL-E in the SDs.

  1. Vitamin D insufficiency is associated with impaired vascular endothelial and smooth muscle function and hypertension in young rats.

    Science.gov (United States)

    Tare, Marianne; Emmett, Sarah J; Coleman, Harold A; Skordilis, Con; Eyles, Darryl W; Morley, Ruth; Parkington, Helena C

    2011-10-01

    Increasing evidence links vitamin D deficiency and cardiovascular dysfunction in human adults. There is a worldwide increase in the prevalence of vitamin D deficiency in women of reproductive age, particularly dark-skinned and/or veiled women and their infants. We used a rat model to determine the functional impact of vitamin D deficiency during intra uterine and early life on resistance artery reactivity and blood pressure in the offspring as young adults. Rat dams were maintained on vitamin D deficient or replete chow before and during pregnancy and lactation. The offspring were maintained on the same chow until studied at 7-8 weeks of age. Conscious blood pressure was measured. Endothelial and smooth muscle function were tested in mesenteric arteries on a pressure myograph. Vitamin D deficient male and female offspring had a 10-fold lower serum 25-hydroxyvitamin D (P < 0.0001) and markedly elevated blood pressures (11-20 mmHg, P < 0.001) and heart rates (21-40 beats min(-1), P < 0.02) than control fed offspring. Serum calcium was unchanged. Mesenteric artery myogenic tone was doubled in vitamin D deficiency. Endothelium-derived nitric oxide-evoked dilation was halved in arteries from vitamin D deficient males and dioestrous females. Dilation attributed to endothelium-derived hyperpolarizing factor was all but abolished in vitamin D deficient oestrous females. Nitroprusside-evoked dilation was unaltered in arteries from males, but was markedly reduced in vessels of vitamin D deplete females. In conclusion, early life vitamin D deficiency is associated with endothelial vasodilator dysfunction, and this is likely to contribute to the accompanying elevation in blood pressure and an increased cardiovascular disease risk.

  2. Arterial endothelial function measurement method and apparatus

    Science.gov (United States)

    Maltz, Jonathan S; Budinger, Thomas F

    2014-03-04

    A "relaxoscope" (100) detects the degree of arterial endothelial function. Impairment of arterial endothelial function is an early event in atherosclerosis and correlates with the major risk factors for cardiovascular disease. An artery (115), such as the brachial artery (BA) is measured for diameter before and after several minutes of either vasoconstriction or vasorelaxation. The change in arterial diameter is a measure of flow-mediated vasomodification (FMVM). The relaxoscope induces an artificial pulse (128) at a superficial radial artery (115) via a linear actuator (120). An ultrasonic Doppler stethoscope (130) detects this pulse 10-20 cm proximal to the point of pulse induction (125). The delay between pulse application and detection provides the pulse transit time (PTT). By measuring PTT before (160) and after arterial diameter change (170), FMVM may be measured based on the changes in PTT caused by changes in vessel caliber, smooth muscle tone and wall thickness.

  3. Circulating Endothelial Microparticles in Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    A. F. Tramontano

    2010-01-01

    Full Text Available Background. Endothelial Microparticles (EMPs are small vesicles shed from activated or apoptotic endothelial cells and involved in cellular cross-talk. Whether EMP immunophenotypes vary according to stimulus in Diabetes Mellitus (DM is not known. We studied the cellular adhesion molecule (CAM profile of circulating EMPs in patients with and without Diabetes Mellitus type 2, who were undergoing elective cardiac catheterization. Methods and Results. EMPs were analyzed by flow cytometry. The absolute median number of EMPs (EMPs/L specific for CD31, CD105, and CD106 was significantly increased in the DM population. The ratio of CD62E/CD31 EMP populations reflected an apoptotic process. Conclusion. Circulating CD31+, CD105+, and CD106+ EMPs were significantly elevated in patients with DM. EMPs were the only independent predictors of DM in our study cohort. In addition, the EMP immunophenotype reflected an apoptotic process. Circulating EMPs may provide new options for risk assessment.

  4. Endothelial Mineralocorticoid Receptor Mediates Parenchymal Arteriole and Posterior Cerebral Artery Remodeling During Angiotensin II-Induced Hypertension.

    Science.gov (United States)

    Diaz-Otero, Janice M; Fisher, Courtney; Downs, Kelsey; Moss, M Elizabeth; Jaffe, Iris Z; Jackson, William F; Dorrance, Anne M

    2017-12-01

    The brain is highly susceptible to injury caused by hypertension because the increased blood pressure causes artery remodeling that can limit cerebral perfusion. Mineralocorticoid receptor (MR) antagonism prevents hypertensive cerebral artery remodeling, but the vascular cell types involved have not been defined. In the periphery, the endothelial MR mediates hypertension-induced vascular injury, but cerebral and peripheral arteries are anatomically distinct; thus, these findings cannot be extrapolated to the brain. The parenchymal arterioles determine cerebrovascular resistance. Determining the effects of hypertension and MR signaling on these arterioles could lead to a better understanding of cerebral small vessel disease. We hypothesized that endothelial MR signaling mediates inward cerebral artery remodeling and reduced cerebral perfusion during angiotensin II (AngII) hypertension. The biomechanics of the parenchymal arterioles and posterior cerebral arteries were studied in male C57Bl/6 and endothelial cell-specific MR knockout mice and their appropriate controls using pressure myography. AngII increased plasma aldosterone and decreased cerebral perfusion in C57Bl/6 and MR-intact littermates. Endothelial cell MR deletion improved cerebral perfusion in AngII-treated mice. AngII hypertension resulted in inward hypotrophic remodeling; this was prevented by MR antagonism and endothelial MR deletion. Our studies suggest that endothelial cell MR mediates hypertensive remodeling in the cerebral microcirculation and large pial arteries. AngII-induced inward remodeling of cerebral arteries and arterioles was associated with a reduction in cerebral perfusion that could worsen the outcome of stroke or contribute to vascular dementia. © 2017 American Heart Association, Inc.

  5. Computational modeling of shear forces and experimental validation of endothelial cell responses in an orbital well shaker system.

    Science.gov (United States)

    Filipovic, Nenad; Ghimire, Kedar; Saveljic, Igor; Milosevic, Zarko; Ruegg, Curzio

    2016-01-01

    Vascular endothelial cells are continuously exposed to hemodynamic shear stress. Intensity and type of shear stress are highly relevant to vascular physiology and pathology. Here, we modeled shear stress distribution in a tissue culture well (R = 17.5 mm, fill volume 2 ml) under orbital translation using computational fluid dynamics with the finite element method. Free surface distribution, wall shear stress, inclination angle, drag force, and oscillatory index on the bottom surface were modeled. Obtained results predict nonuniform shear stress distribution during cycle, with higher oscillatory shear index, higher drag force values, higher circular component, and larger inclination angle of the shear stress at the periphery of the well compared with the center of the well. The oscillatory index, inclination angle, and drag force are new quantitative parameters modeled in this system, which provide a better understanding of the hydrodynamic conditions experienced and reflect the pulsatile character of blood flow in vivo. Validation experiments revealed that endothelial cells at the well periphery aligned under flow and increased Kruppel-like Factor 4 (KLF-4), cyclooxygenase-2 (COX-2) expression and endothelial nitric oxide synthase (eNOS) phosphorylation. In contrast, endothelial cells at the center of the well did not show clear directional alignment, did not induce the expression of KLF-4 and COX-2 nor increased eNOS phosphorylation. In conclusion, this improved computational modeling predicts that the orbital shaker model generates different hydrodynamic conditions at the periphery versus the center of the well eliciting divergent endothelial cell responses. The possibility of generating different hydrodynamic conditions in the same well makes this model highly attractive to study responses of distinct regions of the same endothelial monolayer to different types of shear stresses thereby better reflecting in vivo conditions.

  6. Flow-mediated dilation and peripheral arterial tonometry are disturbed in preeclampsia and reflect different aspects of endothelial function.

    Science.gov (United States)

    Mannaerts, Dominique; Faes, Ellen; Goovaerts, Inge; Stoop, Tibor; Cornette, Jerome; Gyselaers, Wilfried; Spaanderman, Marc; Van Craenenbroeck, Emeline M; Jacquemyn, Yves

    2017-11-01

    Endothelial function and arterial stiffness are known to be altered in preeclamptic pregnancies. Previous studies have shown conflicting results regarding the best technique for assessing vascular function in pregnancy. In this study, we made a comprehensive evaluation of in vivo vascular function [including flow-mediated dilatation (FMD), peripheral arterial tonometry (PAT), and arterial stiffness] in preeclamptic patients and compared them with normal pregnancies. In addition, we assessed the relation between vascular function and systemic inflammation. Fourteen patients with preeclampsia (PE) and 14 healthy pregnant controls were included. Endothelial function was determined by FMD and PAT and arterial stiffness by carotid-femoral pulse-wave velocity and augmentation index. Systemic inflammation was assessed using mean platelet volume (MPV) and neutrophil-lymphocyte ratio (NLR). The reactive hyperemia index, assessed using PAT, is decreased at the third trimester compared with the first trimester in a normal, uncomplicated pregnancy (P = 0.001). Arterial stiffness is significantly higher in PE versus normal pregnancy (P function, obtained by FMD, is deteriorated in PE versus normal pregnancy (P = 0.015), whereas endothelial function assessment by PAT is improved in PE versus normal pregnancy (P = 0.001). Systemic inflammation (MPV and NLR) increases during normal pregnancy. FMD and PAT are disturbed in PE. Endothelial function, assessed by FMD and PAT, shows distinct results. This may indicate that measurements with FMD and PAT reflect different aspects of endothelial function and that PAT should not be used as a substitute for FMD as a measure of endothelial function in pregnancy. Copyright © 2017 the American Physiological Society.

  7. Targeted endothelial nanomedicine for common acute pathological conditions.

    Science.gov (United States)

    Shuvaev, Vladimir V; Brenner, Jacob S; Muzykantov, Vladimir R

    2015-12-10

    Endothelium, a thin monolayer of specialized cells lining the lumen of blood vessels is the key regulatory interface between blood and tissues. Endothelial abnormalities are implicated in many diseases, including common acute conditions with high morbidity and mortality lacking therapy, in part because drugs and drug carriers have no natural endothelial affinity. Precise endothelial drug delivery may improve management of these conditions. Using ligands of molecules exposed to the bloodstream on the endothelial surface enables design of diverse targeted endothelial nanomedicine agents. Target molecules and binding epitopes must be accessible to drug carriers, carriers must be free of harmful effects, and targeting should provide desirable sub-cellular addressing of the drug cargo. The roster of current candidate target molecules for endothelial nanomedicine includes peptidases and other enzymes, cell adhesion molecules and integrins, localized in different domains of the endothelial plasmalemma and differentially distributed throughout the vasculature. Endowing carriers with an affinity to specific endothelial epitopes enables an unprecedented level of precision of control of drug delivery: binding to selected endothelial cell phenotypes, cellular addressing and duration of therapeutic effects. Features of nanocarrier design such as choice of epitope and ligand control delivery and effect of targeted endothelial nanomedicine agents. Pathological factors modulate endothelial targeting and uptake of nanocarriers. Selection of optimal binding sites and design features of nanocarriers are key controllable factors that can be iteratively engineered based on their performance from in vitro to pre-clinical in vivo experimental models. Targeted endothelial nanomedicine agents provide antioxidant, anti-inflammatory and other therapeutic effects unattainable by non-targeted counterparts in animal models of common acute severe human disease conditions. The results of animal

  8. Ionizing radiation activates vascular endothelial growth factor-A transcription in human umbilical vein endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hyounji; Kim, Kwang Seok; Jeong, Jae Hoon; Lim, Young Bin [Radiation Cancer Biology Team, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2016-12-15

    Vascular endothelial growth factor (VEGF) is an essential paracrine factor for developmental and pathological angiogenesis. VEGF also exerts its effects in an autocrine manner in VEGF-producing cells. For instance, autocrine VEGF signaling occurs in tumor cells and contributes to key aspects of tumorigenesis, such as in the function of cancer stem cells and tumor initiation, which are independent of angiogenesis. In addition to tumors cells, non-transformed cells also express VEGF. For example, a VEGF dependent intracellular autocrine mechanism is crucial for the survival of hematopoietic stem cells and hematopoiesis. Stereotactic body radiation therapy (SBRT) is a novel treatment modality for early primary cancer and oligometastatic disease. SBRT delivers high-dose hypofractionated radiation, such as 20-60 Gy, to tumors in a single fraction or 2-5 fractions. As VEGF is a critical regulator of functional integrity and viability of vascular endothelial cells, we examined whether high-dose irradiation alters VEGF signaling by measuring the expression levels of VEGFA transcript. It is generally believed that endothelial cells do not produce VEGF in response to radiation. In present study, however, we provide the first demonstration of transcriptional regulation of VEGFA in human vascular endothelial cells by IR treatment. Irradiation with doses higher than 10 Gy in a single exposure triggers up-regulation of VEGFA transcription within 2 hours in HUVECs, whereas irradiation with 10 Gy does not alter VEGFA levels. Our data have shown that high-dose irradiation triggers immediate transactivation of VEGFA in human vascular endothelial cells.

  9. Metformin improves endothelial function in aortic tissue and microvascular endothelial cells subjected to diabetic hyperglycaemic conditions.

    Science.gov (United States)

    Ghosh, Suparna; Lakshmanan, Arun P; Hwang, Mu Ji; Kubba, Haidar; Mushannen, Ahmed; Triggle, Chris R; Ding, Hong

    2015-12-01

    The cellular mechanisms whereby metformin, the first line drug for type 2 diabetes (T2DM), mediates its antidiabetic effects remain elusive, particularly as to whether metformin has a direct protective action on the vasculature. This study was designed to determine if a brief 3-h exposure to metformin protects endothelial function against the effects of hyperglycaemia. We investigated the protective effects of metformin on endothelial-dependent vasodilatation (EDV) in thoracic aortae from T2DM db/db mice and on high glucose (HG, 40 mM) induced changes in endothelial nitric oxide synthase (eNOS) signaling in mouse microvascular endothelial cells (MMECs) in culture. Exposure of aortae from db+/? non-diabetic control mice to high glucose (HG, 40 mM) containing Krebs for 3-h significantly (Pmetformin; metformin also improved ACh-induced EDV in aortae from diabetic db/db mice. Immunoblot analysis of MMECs cultured in HG versus NG revealed a significant reduction of the ratio of phosphorylated (p-eNOS)/eNOS and p-Akt/Akt, but not the expression of total eNOS or Akt. The 3-h exposure of MMECs to metformin significantly (Pmetformin can reverse/reduce the impact of HG on endothelial function, via mechanisms linked to increased phosphorylation of eNOS and Akt. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Brain endothelial dysfunction in cerebral adrenoleukodystrophy.

    Science.gov (United States)

    Musolino, Patricia L; Gong, Yi; Snyder, Juliet M T; Jimenez, Sandra; Lok, Josephine; Lo, Eng H; Moser, Ann B; Grabowski, Eric F; Frosch, Matthew P; Eichler, Florian S

    2015-11-01

    See Aubourg (doi:10.1093/awv271) for a scientific commentary on this article.X-linked adrenoleukodystrophy is caused by mutations in the ABCD1 gene leading to accumulation of very long chain fatty acids. Its most severe neurological manifestation is cerebral adrenoleukodystrophy. Here we demonstrate that progressive inflammatory demyelination in cerebral adrenoleukodystrophy coincides with blood-brain barrier dysfunction, increased MMP9 expression, and changes in endothelial tight junction proteins as well as adhesion molecules. ABCD1, but not its closest homologue ABCD2, is highly expressed in human brain microvascular endothelial cells, far exceeding its expression in the systemic vasculature. Silencing of ABCD1 in human brain microvascular endothelial cells causes accumulation of very long chain fatty acids, but much later than the immediate upregulation of adhesion molecules and decrease in tight junction proteins. This results in greater adhesion and transmigration of monocytes across the endothelium. PCR-array screening of human brain microvascular endothelial cells after ABCD1 silencing revealed downregulation of both mRNA and protein levels of the transcription factor c-MYC (encoded by MYC). Interestingly, MYC silencing mimicked the effects of ABCD1 silencing on CLDN5 and ICAM1 without decreasing the levels of ABCD1 protein itself. Together, these data demonstrate that ABCD1 deficiency induces significant alterations in brain endothelium via c-MYC and may thereby contribute to the increased trafficking of leucocytes across the blood-brain barrier as seen in cerebral adrenouleukodystrophy. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. Corneal Donor Tissue Preparation for Endothelial Keratoplasty

    OpenAIRE

    Woodward, Maria A.; Titus, Michael; Mavin, Kyle; Shtein, Roni M.

    2012-01-01

    Over the past ten years, corneal transplantation surgical techniques have undergone revolutionary changes1,2. Since its inception, traditional full thickness corneal transplantation has been the treatment to restore sight in those limited by corneal disease. Some disadvantages to this approach include a high degree of post-operative astigmatism, lack of predictable refractive outcome, and disturbance to the ocular surface. The development of Descemet's stripping endothelial keratoplasty (DSEK...

  12. Endothelial microparticles (EMP in physiology and pathology

    Directory of Open Access Journals (Sweden)

    Ewa Sierko

    2015-08-01

    Full Text Available Endothelial microparticles (EMP are released from endothelial cells (ECs in the process of activation and/or apoptosis. They harbor adhesive molecules, enzymes, receptors and cytoplasmic structures and express a wide range of various constitutive antigens, typical for ECs, at their surface. Under physiological conditions the concentration of EMP in the blood is clinically insignificant. However, it was reported that under pathological conditions EMP concentration in the blood might slightly increase and contribute to blood coagulation, angiogenesis and inflammation. It has been shown that EMP directly and indirectly contribute to the activation of blood coagulation. Endothelial microparticles directly participate in blood coagulation through their surface tissue factor (TF – a major initiator of blood coagulation. Furthermore, EMP exhibit procoagulant potential via expression of negatively charged phospholipids at their surface, which may promote assembly of coagulation enzymes (TF/VII, tenases and prothrombinase complexes, leading to thrombus formation. In addition, they provide a binding surface for coagulation factors: IXa, VIII, Va and IIa. Moreover, it is possible that EMP transfer TF from TF-bearing EMP to activated platelets and monocytes by binding them through adhesion molecules. Also, EMP express von Willebrand factor, which may facilitate platelet aggregation. Apart from their procoagulant properties, it was demonstrated that EMP may express adhesive molecules and metalloproteinases (MMP-2, MMP-9 at their surface and release growth factors, which may contribute to angiogenesis. Additionally, surface presence of C3 and C4 – components of the classical pathway – suggests pro-inflammatory properties of these structures. This article contains a summary of available data on the biology and pathophysiology of endothelial microparticles and their potential role in blood coagulation, angiogenesis and inflammation.

  13. Arecoline is cytotoxic for human endothelial cells.

    Science.gov (United States)

    Ullah, Mafaz; Cox, Stephen; Kelly, Elizabeth; Boadle, Ross; Zoellner, Hans

    2014-11-01

    Oral submucous fibrosis is a pre-malignant fibrotic condition caused by areca nut use and involves reduced mucosal vascularity. Arecoline is the principal areca nut alkaloid and is cytotoxic for epithelium and fibroblasts. Endothelial cell cycle arrest is reported on exposure to arecoline, as is cytotoxicity for endothelial-lung carcinoma hybrid cells. We here describe cytotoxicity for primary human endothelial cultures from seven separate donors. Human umbilical vein endothelial cells were exposed to increasing concentrations of arecoline and examined by: phase-contrast microscopy, haemocytometer counts, transmission electron microscopy, lactate dehydrogenase release and the methyl-thiazol-tetrazolium assay. Vacuolation and detachment of endothelium were observed at and above arecoline concentrations of 333 μg/ml or more. Ultrastructural features of cellular stress were seen after 24-h treatment with 111 μg/ml arecoline and included reduced ribosomal studding of endoplasmic reticulum, increased autophagolysosomal structures, increased vacuolation and reduced mitochondrial cristae with slight swelling. Similar changes were seen at 4 h with arecoline at 333 μg/ml or above, but with more severe mitochondrial changes including increased electron density of mitochondrial matrix and greater cristal swelling, while by 24 h, these cells were frankly necrotic. Haemocytometer counts were paralleled by both lactate dehydrogenase release and the methyl-thiazol-tetrazolium assays. Arecoline is cytotoxic via necrosis for endothelium, while biochemical assays indicate no appreciable cellular leakage before death and detachment, as well as no clear effect on mitochondrial function in viable cells. Arecoline toxicity may thus contribute to reduced vascularity in oral submucous fibrosis. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Sulforaphane reduces advanced glycation end products (AGEs)-induced inflammation in endothelial cells and rat aorta.

    Science.gov (United States)

    Matsui, T; Nakamura, N; Ojima, A; Nishino, Y; Yamagishi, S-I

    2016-09-01

    Advanced glycation end products (AGEs)-receptor RAGE interaction evokes oxidative stress and inflammatory reactions, thereby being involved in endothelial cell (EC) damage in diabetes. Sulforaphane is generated from glucoraphanin, a naturally occurring isothiocyanate found in widely consumed cruciferous vegetables, by myrosinase. Sulforaphane has been reported to protect against oxidative stress-mediated cell and tissue injury. However, effects of sulforaphane on AGEs-induced vascular damage remain unclear. In this study, we investigated whether and how sulforaphane could inhibit inflammation in AGEs-exposed human umbilical vein ECs (HUVECs) and AGEs-injected rat aorta. Sulforaphane treatment for 4 or 24 h dose-dependently inhibited the AGEs-induced increase in RAGE, monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecular-1 (VCAM-1) gene expression in HUVECs. AGEs significantly stimulated MCP-1 production by, and THP-1 cell adhesion to, HUVECs, both of which were prevented by 1.6 μM sulforaphane. Sulforaphane significantly suppressed oxidative stress generation and NADPH oxidase activation evoked by AGEs in HUVECs. Furthermore, aortic RAGE, ICAM-1 and VCAM-1 expression in AGEs-injected rats were increased, which were suppressed by simultaneous infusion of sulforaphane. The present study demonstrated for the first time that sulforaphane could inhibit inflammation in AGEs-exposed HUVECs and AGEs-infused rat aorta partly by suppressing RAGE expression through its anti-oxidative properties. Inhibition of the AGEs-RAGE axis by sulforaphane might be a novel therapeutic target for vascular injury in diabetes. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

  15. The Dual Edema-Preventing Molecular Mechanism of the Crataegus Extract WS 1442 Can Be Assigned to Distinct Phytochemical Fractions.

    Science.gov (United States)

    Fuchs, Simone; Bischoff, Iris; Willer, Elisabeth A; Bräutigam, Jacqueline; Bubik, Martin F; Erdelmeier, Clemens A J; Koch, Egon; Faleschini, Maria T; De Mieri, Maria; Bauhart, Milena; Zahler, Stefan; Hensel, Andreas; Hamburger, Matthias; Potterat, Olivier; Fürst, Robert

    2017-05-01

    The hawthorn (Crataegus spp.) extract WS 1442 is used against mild forms of chronic heart failure. This disease is associated with endothelial barrier dysfunction and edema formation. We have recently shown that WS 1442 protects against this dysfunction by a dual mechanism: it both promotes endothelial barrier integrity by activation of a barrier-enhancing pathway (cortactin activation) and inhibits endothelial hyperpermeability by blocking a barrier disruptive pathway (calcium signaling). In this study, we aimed to identify the bioactive compounds responsible for these actions by using a bioactivity-guided fractionation approach. From the four fractions generated from WS 1442 by successive elution with water, 95 % ethanol, methanol, and 70 % acetone, only the water fraction was inactive, whereas the other three triggered a reduction of endothelial hyperpermeability. Analyses of intracellular calcium levels and cortactin phosphorylation were used as readouts to estimate the bioactivity of subfractions and isolated compounds. Interestingly, only the ethanolic fraction interfered with the calcium signaling, whereas only the methanolic fraction led to an activation of cortactin. Thus, the dual mode of action of WS 1442 could be clearly assigned to two distinct fractions. Although the identification of the calcium-active substance(s) was not successful, we could exclude an involvement of phenolic compounds. Cortactin activation, however, could be clearly attributed to oligomeric procyanidins with a distinct degree of polymerization. Taken together, our study provides the first approach to identify the active constituents of WS 1442 that address different cellular pathways leading to the inhibition of endothelial barrier dysfunction. Georg Thieme Verlag KG Stuttgart · New York.

  16. Descemet membrane endothelial keratoplasty and refractive surgery.

    Science.gov (United States)

    Tong, C Maya; Baydoun, Lamis; Melles, Gerrit R J

    2017-07-01

    Descemet membrane endothelial keratoplasty (DMEK) has become a first-line treatment in corneal endothelial diseases because of its exceptional clinical outcomes and low complication rates. Because of its improved refractive predictability, DMEK is now also considered for managing cases with endothelial decompensation following previous refractive procedures, or in combination with those. This article reviews the clinical outcomes in these cases and discusses the possibility of refractive interventions following DMEK. DMEK has been successfully performed in eyes after laser in-situ keratomileusis, eyes after anterior chamber intraocular lens (IOL) implantation and aphakic eyes. Often, DMEK is combined with cataract surgery (triple-DMEK). Initial reports on reducing the refractive cylinder by toric IOL implantation are available. Although there are some reports on phacoemulsification and IOL implantation after phakic DMEK, reports on laser refractive procedures following DMEK are lacking. In contrast to earlier keratoplasty techniques, DMEK induces on average only mild refractive shifts owing to the 'natural' restoration of the cornea. As such, DMEK may be ideal in managing corneal decompensation in refractive patients. However, further studies are required to assess the safety and efficacy of DMEK after refractive treatment and of refractive procedures following DMEK.

  17. Doinseunggitang Ameliorates Endothelial Dysfunction in Diabetic Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Jung Joo Yoon

    2013-01-01

    Full Text Available Atherosclerosis, a chronic and progressive disease characterized by vascular inflammation, is a leading cause of death in diabetes patients. Doinseunggitang (DYSGT, traditional prescription, has been used for promoting blood circulation to remove blood stasis. The aim of this study was to investigate the beneficial effects of DYSGT on endothelial dysfunction in diabetic atherosclerosis animal model. Apolipoprotein E knockout (ApoE KO mice fed on a Western diet were treated with DYSGT (200 mg/kg/day. DYSGT significantly lowered blood glucose level and glucose tolerance as well as systolic blood pressure. Metabolic parameter showed that DYSGT markedly decreased triglyceride and LDL-cholesterol levels. In the thoracic aorta, the impairment of vasorelaxation response to acetylcholine and atherosclerotic lesion was attenuated by DYSGT. Furthermore, DYSGT restored the reduction of endothelial nitric oxide synthase (eNOS expression, leading to the inhibition of intracellular adhesion molecule-1 (ICAM-1 and endothelin-1 (ET-1 expression. In conclusion, DYSGT improved the development of diabetic atherosclerosis via attenuation of the endothelial dysfunction, possibly by inhibiting ET-1, cell adhesion molecules, and lesion formation. Therefore, these results suggest that Korean traditional prescription Doinseunggitang may be useful in the treatment and prevention of diabetic vascular complications.

  18. Protective effects of Donepezil against endothelial permeability.

    Science.gov (United States)

    Tang, Xuelu; Di, Xiuhua; Liu, Yilin

    2017-09-15

    The endothelium lines the interior surface of blood vessels, and under pathophysiologic conditions, its integrity can be compromised due to a disturbance in the expression of tight junctions. Donepezil is a licensed drug used in the palliative treatment of Alzheimer's disease (AD). Increasing evidence has reported that donepezil has an anti-inflammatory activity. However, little information is available regarding the role of donepezil in vascular diseases. In this study, we found that pretreatment with donepezil significantly ameliorated endothelial permeability induced by tumor necrosis factor (TNF-α) by restoring the expression of the tight junction proteins vascular endothelial cadherin (VE-cadherin) and zonula occludens-1 (ZO-1) in human umbilical vein endothelial cells (HUVECs). Mechanistically, our results indicate that donepezil regulates the expression and activity of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinases 1 (TIMP-1), but not matrix metalloproteinase-2 (MMP-2) or tissue inhibitor of metalloproteinases 2 (TIMP-2). Importantly, the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/ serine-threonine kinase (AKT)/ nuclear factor kappa B (NF-κB) pathway was found to be involved in this process. These results suggest that donepezil may potentially play an important therapeutic role in vascular diseases. Copyright © 2017. Published by Elsevier B.V.

  19. [Auditory evoked potential and personality traits in chronic primary insomniacs].

    Science.gov (United States)

    Shen, Jian; Shui, Ren-de; Feng, Lei; Liu, Yu-Hong; He, Wei; Huang, Jing-Yi; Wang, Wei

    2009-05-01

    To investigate the personality traits and intensity dependence of auditory evoked potentials (AEPs) in chronic primary insomnia. Thirty-seven patients with chronic primary insomnia (insomnia group) and 44 healthy subjects (control group) were enrolled in the study. The AEPs were examined in insomnia and control groups; the personality traits were studied by Zuckerman's Sensation Seeking Scales (SSS) and Zuckerman-Kuhlman's Personality Questionnaire (ZKPQ); and the mood states by Plutchik-van Praag's Depression Inventory (PVP). The scores of neuroticism-anxiety and depression in insomnia group were significantly higher than those in control group (P<0.01); and the scores of impulsivity and aggression-hostility were also higher than those in control group (P<0.05); N1-P2 amplitude of AEP increased with stimulus intensity, which were significantly different in 70, 80, 90,100 dB (P<0.01). There were significant correlations between activity and N1 latency at 80 dB, activity and P2 latency at 100 dB (r=0.270, r=0.276, P<0.05); and between total scores of sensation seeking scale and N1-P2 amplitude (r=0.3746, r=0.35329, P<0.01) at 70 and 90 dB stimulus intensity in insomnia group. There were significant correlations among experience seeking and N1-P2 amplitude, experience seeking and slope rate (P<0.01) at 70, 80, 90, 100 dB stimulus intensity in insomnia group (r=0.539, r=0.3439, r=0.439, r=0.3278). There were significant correlations between sensation seeking of boredom susceptibility and slope rate (r=-0.282998, P<0.05) in insomnia group. There were significant correlations between thrill and adventure seeking and N1-P2 amplitude(r=0.2789, P<0.05) at 90 dB stimulus intensity in insomnia group; there were significant correlations between PVP and N1-P2 amplitude (r=-0.3434, r=-0.3158, P<0.05) at 70 dB and N1 latency at 80 dB in insomnia group. Chronic primary insomnia sufferers have higher levels of neuroticism-anxiety, depression, aggression-hostility and impulsivity

  20. Fluorescent tube light evokes flicker responses in visual neurons.

    Science.gov (United States)

    Eysel, U T; Burandt, U

    1984-01-01

    Single neurons in the cat visual system respond distinctly to the temporal information present in light from fluorescent tubes driven by 50 or 60 Hz alternating current. Despite the resulting flicker frequencies of 100 or 120 Hz all retinal and most thalamic neurons show strong phase locking of the neuronal responses to the modulation of fluorescent tube light. Some retinal ganglion cells have not yet reached their critical flicker fusion frequency under such conditions. Though usually beyond perception, the frequency and depth of modulation of artificial light thus might well play a role in biological light effects.

  1. Nitric oxide and hypoxia stimulate erythropoietin receptor via MAPK kinase in endothelial cells.

    Science.gov (United States)

    Cokic, Bojana B Beleslin; Cokic, Vladan P; Suresh, Sukanya; Wirt, Stacey; Noguchi, Constance Tom

    2014-03-01

    Erythropoietin receptor (EPOR) expression level determines the extent of erythropoietin (EPO) response. Previously we showed that EPOR expression in endothelial cells is increased at low oxygen tension and that EPO stimulation of endothelial cells during hypoxia can increase endothelial nitric oxide (NO) synthase (eNOS) expression and activation as well as NO production. We now observe that while EPO can stimulate NO production, NO in turn can regulate EPOR expression. Human umbilical vein endothelial cells (HUVEC) treated with 10-50 μM of NO donor diethylenetriamine NONOate (DETANO) for 24h showed significant induction of EPOR gene expression at 5% and 2% of oxygen. Also human bone marrow microvascular endothelial cell line (TrHBMEC) cultured at 21 and 2% oxygen with 50 μM DETANO demonstrated a time and oxygen dependent induction of EPOR mRNA expression after 24 and 48 h, particularly at low oxygen tension. EPOR protein was also induced by DETANO at 2% oxygen in TrHBMEC and HUVEC. The activation of signaling pathways by NO donor stimulation appeared to be distinct from EPO stimulation. In reporter gene assays, DETANO treatment of HeLa cells at 2% oxygen increased EPOR promoter activity indicated by a 48% increase in luciferase activity with a 2 kb EPOR promoter fragment and a 71% increase in activity with a minimal EPOR promoter fragment containing 0.2 kb 5'. We found that DETANO activated MAPK kinase in TrHBMEC both in normoxia and hypoxia, while MAPK kinase inhibition showed significant reduction of EPOR mRNA gene expression at low oxygen tension, suggesting MAPK involvement in NO mediated induction of EPOR. Furthermore, DETANO stimulated Akt anti-apoptotic activity after 30 min in normoxia, whereas it inhibited Akt phosphorylation in hypoxia. In contrast, EPO did not significantly increase MAPK activity while EPO stimulated Akt phosphorylation in TrHBMEC in normoxia and hypoxia. These observations provide a new effect of NO on EPOR expression to enhance EPO

  2. Unpredictable Chronic Mild Stress Paradigm Established Effects of Pro- and Anti-inflammatory Cytokine on Neurodegeneration-Linked Depressive States in Hamsters with Brain Endothelial Damages.

    Science.gov (United States)

    Avolio, Ennio; Fazzari, Gilda; Mele, Maria; Alò, Raffaella; Zizza, Merylin; Jiao, Wei; Di Vito, Anna; Barni, Tullio; Mandalà, Maurizio; Canonaco, Marcello

    2017-10-01

    The mechanisms by which inflammation affects the different emotional moods are only partially known. Previous works have pointed to stress hormones like glucocorticoids plus the vascular factor endothelin-1 as key factors evoking stressful states especially in relation to endothelial dysfunctions. With this work, it was our intention to establish the role of pro- and anti-inflammatory cytokine expression variations towards depression-like behaviors and consequently the development of neurodegeneration events caused by endothelial damages in the hamster (Mesocricetus auratus). Such a rodent, which is considered a valuable animal model to test depression and anxiety states, exhibited a variety of depression-like behaviors including reduction in sucrose consumption, locomotion, and exploration (p < 0.01) following exposure to unpredictable chronic mild stress. Contextually, a tight correlation between unpredictable chronic mild stress-induced depressive states and expression of the pro-inflammatory cytokines was detected as shown by marked expression levels (p < 0.01) of IL-1β and NF-kB in the hippocampus, amygdala, and prefrontal cortex. Even the anti-inflammatory cytokine IL-10 supplied notably significant (p < 0.001) expression levels in the same areas of resilient hamsters. Application of hemodynamic and endothelial functional studies pointed to altered arterial endothelial activities in depressed with respect to resilient animals. Moreover, evident damaged neuronal fields in the above areas of depressed hamsters allowed us to correlate such a behavioral phenomenon to the upregulation of IL-1β and NF-κB. Overall, the differing roles of pro- and anti-inflammatory cytokines on depressive states, especially in view of brain endothelial damages, may provide novel therapeutic measures against mood disorders linked to neurodegenerative diseases.

  3. Conserved signaling through vascular endothelial growth (VEGF) receptor family members in murine lymphatic endothelial cells.

    Science.gov (United States)

    Coso, Sanja; Zeng, Yiping; Sooraj, Dhanya; Williams, Elizabeth D

    2011-10-15

    Lymphatic vessels guide interstitial fluid, modulate immune responses by regulating leukocyte and antigen trafficking to lymph nodes, and in a cancer setting enable tumor cells to track to regional lymph nodes. The aim of the study was to determine whether primary murine lymphatic endothelial cells (mLECs) show conserved vascular endothelial growth factor (VEGF) signaling pathways with human LECs (hLECs). LECs were successfully isolated from murine dermis and prostate. Similar to hLECs, vascular endothelial growth factor (VEGF) family ligands activated MAPK and pAkt intracellular signaling pathways in mLECs. We describe a robust protocol for isolation of mLECs which, by harnessing the power of transgenic and knockout mouse models, will be a useful tool to study how LEC phenotype contributes to alterations in lymphatic vessel formation and function. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

  4. Tumor Microvasculature: Endothelial Leakiness and Endothelial Pore Size Distribution in a Breast Cancer Model

    Directory of Open Access Journals (Sweden)

    E.E. Uzgiris

    2008-01-01

    Full Text Available Tumor endothelial leakiness is quantified in a rat mammary adenocarcinoma model using dynamic contrast enhancement MRI and contrast agents of widely varying sizes. The contrast agents were constructed to be of globular configuration and have their uptake rate into tumor interstitium be driven by the same diffusion process and limited only by the availability of endothelial pores of passable size. It was observed that the endothelial pore distribution has a steep power law dependence on size, r−β, with an exponent of −4.1. The model of large pore dominance in tumor leakiness as reported in some earlier investigation with fluorescent probes and optical chamber methods is rejected for this tumor model and a number of other tumor types including chemically induced tumors. This steep power law dependence on size is also consistent with observations on human breast cancer.

  5. Microvascular endothelial dysfunction is associated with albuminuria and CKD in older adults.

    Science.gov (United States)

    Seliger, Stephen L; Salimi, Shabnam; Pierre, Valerie; Giffuni, Jamie; Katzel, Leslie; Parsa, Afshin

    2016-07-13

    Impairment in glomerular endothelial function likely plays a major role in the development of albuminuria and CKD progression. Glomerular endothelial dysfunction may reflect systemic microvascular dysfunction, accounting in part for the greater cardiovascular risk in patients with albuminuria. Prior studies of vascular function in CKD have focused on conduit artery function or those with ESRD, and have not examined microvascular endothelial function with albuminuria. We conducted a cross-sectional study among older hypertensive male veterans with stage 1-4 CKD, and hypertensive controls without CKD. Microvascular function was quantified by two distinct Laser-Doppler flowmetry (LDF) measures: peak responses to 1) post-occlusive reactive hyperemia (PORH) and 2) thermal hyperemia (TH), measured on forearm skin. Associations of each LDF measure with albuminuria, eGFR, and CKD status were estimated using correlation coefficients and multiple linear regression, accounting for potential confounders. Among 66 participants (mean age 69.2 years), 36 had CKD (mean eGFR 46.1 cc/min/1.73 m(2); 30.6 % with overt albuminuria). LDF responses to PORH and TH were 43 and 39 % significantly lower in multivariate analyses among those with macroalbuminuria compared to normoalbuminuria, (β= - 0.42, p = 0.009 and β= -0.37, p = 0.01, respectively). Those with CKD had a 23.9 % lower response to PORH compared to controls (p = 0.02 after adjustment). In contrast, TH responses did not differ between those with and without CKD. Microvascular endothelial function was strongly associated with greater albuminuria and CKD, independent of diabetes and blood pressure. These findings may explain in part the excess systemic cardiovascular risk associated with albuminuria and CKD.

  6. Smooth muscle progenitor cells from peripheral blood promote the neovascularization of endothelial colony-forming cells

    Energy Technology Data Exchange (ETDEWEB)

    Joo, Hyung Joon; Seo, Ha-Rim [Department of Cardiology, Cardiovascular Center, College of Medicine, Korea University, Seoul (Korea, Republic of); Jeong, Hyo Eun [Department of Mechanical Engineering, Korea University, Seoul (Korea, Republic of); Choi, Seung-Cheol; Park, Jae Hyung; Yu, Cheol Woong; Hong, Soon Jun [Department of Cardiology, Cardiovascular Center, College of Medicine, Korea University, Seoul (Korea, Republic of); Chung, Seok [Department of Mechanical Engineering, Korea University, Seoul (Korea, Republic of); Lim, Do-Sun, E-mail: dslmd@kumc.or.kr [Department of Cardiology, Cardiovascular Center, College of Medicine, Korea University, Seoul (Korea, Republic of)

    2014-07-11

    Highlights: • Two distinct vascular progenitor cells are induced from adult peripheral blood. • ECFCs induce vascular structures in vitro and in vivo. • SMPCs augment the in vitro and in vivo angiogenic potential of ECFCs. • Both cell types have synergistic therapeutic potential in ischemic hindlimb model. - Abstract: Proangiogenic cell therapy using autologous progenitors is a promising strategy for treating ischemic disease. Considering that neovascularization is a harmonized cellular process that involves both endothelial cells and vascular smooth muscle cells, peripheral blood-originating endothelial colony-forming cells (ECFCs) and smooth muscle progenitor cells (SMPCs), which are similar to mature endothelial cells and vascular smooth muscle cells, could be attractive cellular candidates to achieve therapeutic neovascularization. We successfully induced populations of two different vascular progenitor cells (ECFCs and SMPCs) from adult peripheral blood. Both progenitor cell types expressed endothelial-specific or smooth muscle-specific genes and markers, respectively. In a protein array focused on angiogenic cytokines, SMPCs demonstrated significantly higher expression of bFGF, EGF, TIMP2, ENA78, and TIMP1 compared to ECFCs. Conditioned medium from SMPCs and co-culture with SMPCs revealed that SMPCs promoted cell proliferation, migration, and the in vitro angiogenesis of ECFCs. Finally, co-transplantation of ECFCs and SMPCs induced robust in vivo neovascularization, as well as improved blood perfusion and tissue repair, in a mouse ischemic hindlimb model. Taken together, we have provided the first evidence of a cell therapy strategy for therapeutic neovascularization using two different types of autologous progenitors (ECFCs and SMPCs) derived from adult peripheral blood.

  7. Molecular sieving characteristics of the cultured endothelial monolayer.

    Science.gov (United States)

    Siflinger-Birnboim, A; Del Vecchio, P J; Cooper, J A; Blumenstock, F A; Shepard, J M; Malik, A B

    1987-07-01

    We examined the selectivity of the bovine pulmonary artery endothelial monolayer in vitro to molecules of different sizes. The cultured bovine pulmonary endothelial monolayer was grown on a gelatinized filter and the transendothelial transport was studied by determining the permeability of molecules ranging from 182 to 340,000 daltons under diffusion conditions. The permeabilities across the cultured bovine endothelium were modeled according to cylindrical pore theory. The data were best fit by a two-pore model with radii 65 A and 304 A and a ratio of small to large pores of 160:1. The results indicate that the cultured endothelial monolayer is a selective barrier to molecules of different sizes and that the molecular selectivity is consistent with a diffusional pathway through endothelial pore equivalents. The cultured endothelial monolayer is a useful system for studying the permeability characteristics of the endothelial barrier.

  8. Receptor-Mediated Transport of Insulin across Endothelial Cells

    Science.gov (United States)

    King, George L.; Johnson, Sandra M.

    1985-03-01

    Hormones such as insulin are transported from the interior to the exterior of blood vessels. Whether endothelial cells, which line the inner walls of blood vessels have a role in this transport of hormones is not clear, but it is known that endothelial cells can internalize and release insulin rapidly with little degradation. The transport of iodine-125-labeled insulin was measured directly through the use of dual chambers separated by a horizontal monolayer of cultured bovine aortic endothelial cells. In this setting, endothelial cells took up and released the labeled insulin, thereby transporting it across the cells. The transport of insulin across the endothelial cells was temperature sensitive and was inhibited by unlabeled insulin and by antibody to insulin receptor in proportion to the ability of these substances to inhibit insulin binding to its receptor. More than 80 percent of the transported insulin was intact. These data suggest that insulin is rapidly transported across endothelial cells by a receptor-mediated process.

  9. Descemet stripping and endothelial keratoplasty in endothelial dysfunctions: Three-month results in 75 eyes

    Directory of Open Access Journals (Sweden)

    Basak Samar

    2008-01-01

    Full Text Available Purpose: To analyze the results of Descemet stripping and endothelial keratoplasty (DSEK in the first consecutive 75 cases. Materials and Methods: Prospective, non-randomized, non-comparative interventional case series. Seventy-five eyes of 75 patients with endothelial dysfunctions of different etiology, scheduled for DSEK, were included in this study. Healthy donor cornea with a cell count of> 2000 cells/sq mm was considered for transplantation in each case. Indications, operative problems and postoperative complications were noted. Best corrected visual acuity (BCVA, refractive and keratometric astigmatism, central corneal thickness (CCT and endothelial cell density (ECD were analyzed for each patient after a minimum follow-up of three months. Results: Main indication was pseudophakic corneal edema and bullous keratopathy in 53 (70.7% eyes. Seventeen (22.7% cases had moderate to severe Fuchs′ dystrophy with various grades of cataract; and DSEK was combined with manual small-incision cataract surgery (MSICS with posterior chamber intraocular lens (PCIOL in those cases. After three months, BCVA was 20/60 or better in 62 (82.7% cases. Mean refractive and keratometric astigmatism were 1.10 ± 0.55 diopter cylinder (DCyl and 1.24 ± 0.92 DCyl. The CCT and ECD were 670.8 ± 0.32 µm and 1485.6 ± 168.6/sq mm respectively. The mean endothelial cell loss after three months was 26.8 ± 4.24% (range: 13.3-38.4%. Dislocation of donor lenticule occurred in six (8.0% eyes. Graft failure occurred in one case. Conclusions: Descemet stripping and endothelial keratoplasty is a safe and effective procedure in patients with endothelial dysfunctions with encouraging surgical and visual outcomes. It can be safely combined with MSICS with PCIOL in patients with moderate to severe Fuchs′ dystrophy with cataract.

  10. Soluble endothelial cell molecules and circulating endothelial cells in patients with venous thromboembolism.

    Science.gov (United States)

    Torres, Cláudia; Matos, Rui; Morais, Sara; Campos, Manuel; Lima, Margarida

    2017-12-01

    : To evaluate the plasma levels of soluble endothelial cell molecules in patients with venous thromboembolism (VTE) out of the acute phase as compared with healthy individuals. We also investigated the possible associations of the soluble endothelial cell molecules among them, as well as with other clinical and laboratory data, including the numbers of circulating endothelial cells (CEC), circulating endothelial progenitor cells (CEP), and CEC expressing activation-related [cluster of differentiation (CD)54 and CD62E] and procoagulant (CD142) markers. In total, 15 patients with VTE and 20 normal individuals were studied. The CEC and CEP were quantified and characterized by flow cytometry. The soluble molecules studied included P-selectin, E-selectin, intercellular cell adhesion molecule 1, vascular cell adhesion molecule 1 and tissue factor (ELISA), and von Willebrand factor antigen (immunoturbidimetry). VTE patients had significantly higher levels of vascular cell adhesion molecule 1 and von Willebrand factor antigen and lower levels of soluble E-selectin than controls. They also showed significantly higher numbers of CEC, as of activated/procoagulant CEC and lower numbers of CEP, compared with controls. We did not find any correlation between the levels of soluble molecules and the numbers of endothelial cell in circulation, but there was with several clinical and laboratory data in VTE patients. Our results would suggest that in VTE patients, the endothelium remains activated and in some hypercoagulable state. The levels of soluble endothelial cell molecules did not seem to be directly related to the numbers of CEC and CEP neither reflected the number of activated CEC, which may be because of the different function that surface and soluble molecules may have.

  11. Vochysia rufa Stem Bark Extract Protects Endothelial Cells against High Glucose Damage.

    Science.gov (United States)

    Moura de Gouveia, Neire; Ramos, Sonia; Martín, María Ángeles; Espindola, Foued Salmen; Goya, Luis; Palomino, Olga M

    2017-02-21

    Background: Increased oxidative stress by persistent hyperglycemia is a widely accepted factor in vascular damage responsible for type 2 diabetes complications. The plant Vochysia rufa (Vr) has been used in folk medicine in Brazil for the treatment of diabetes. Thus; the protective effect of a Vr stem bark extract against a challenge by a high glucose concentration on EA.hy926 (EA) endothelial cells is evaluated. Methods: Vegetal material is extracted with distilled water by maceration and evaporated until dryness under vacuum. Then; it is isolated by capillary electrophoresis-tandem mass spectrometry. Cell viability is evaluated on EA cells treated with 0.5-100 µg/mL of the Vr extract for 24 h. The extract is diluted at concentrations of 5, 10 and 25 µg/mL and maintained for 24 h along with 30 mM of glucose to evaluate its protective effect on reduced glutathione (GSH); glutathione peroxidase (GPx) and reductase (GR) and protein carbonyl groups. Results:V. rufa stem bark is composed mainly of sugars; such as inositol; galactose; glucose; mannose; sacarose; arabinose and ribose. Treatment with Vr up to 100 µg/mL for 24 h did not affect cell viability. Treatment of EA cells with 30 mM of glucose for 24 h significantly increased the cell damage. EA cells treated with 30 mM of glucose showed a decrease of GSH concentration and increased Radical Oxygen Species (ROS) and activity of antioxidant enzymes and protein carbonyl levels; compared to control. Co-treatment of EA with 30 mM glucose plus 1-10 μg/mL Vr significantly reduced cell damage while 5-25 μg/mL Vr evoked a significant protection against the glucose insult; recovering ROS; GSH; antioxidant enzymes and carbonyls to baseline levels. Conclusion:V. rufa extract protects endothelial cells against oxidative damage by modulating ROS; GSH concentration; antioxidant enzyme activity and protein carbonyl levels.

  12. Isoflurane reduces the carbachol-evoked Ca2+ influx in neuronal cells.

    Science.gov (United States)

    Corrales, Alexandra; Xu, Fang; Garavito-Aguilar, Zayra V; Blanck, Thomas J J; Recio-Pinto, Esperanza

    2004-10-01

    The authors previously reported that the isoflurane-caused reduction of the carbachol-evoked cytoplasmic Ca transient increase ([Ca]cyt) was eliminated by K or caffeine-pretreatment. In this study the authors investigated whether the isoflurane-sensitive component of the carbachol-evoked [Ca]cyt transient involved Ca influx through the plasma membrane. Perfused attached human neuroblastoma SH-SY5Y cells were exposed to carbachol (1 mm, 2 min) in the absence and presence of isoflurane (1 mm) and in the absence and presence of extracellular Ca (1.5 mm). The authors studied the effect of the nonspecific cationic channel blocker La (100 microm), of the L-type Ca channel blocker nitrendipine (10 microm), and of the N-type Ca channel blocker omega-conotoxin GVIA (0.1 microm) on isoflurane modulation of the carbachol-evoked [Ca]cyt transient. [Ca]cyt was detected with fura-2 and experiments were carried out at 37 degrees C. Isoflurane reduced the peak and area of the carbachol-evoked [Ca]cyt transient in the presence but not in the absence of extracellular Ca. La had a similar effect as the removal of extracellular Ca. Omega-conotoxin GVIA and nitrendipine did not affect the isoflurane sensitivity of the carbachol response although nitrendipine reduced the magnitude of the carbachol response. The current data are consistent with previous observations in that the carbachol-evoked [Ca]cyt transient involves both Ca release from intracellular Ca stores and Ca entry through the plasma membrane. It was found that isoflurane attenuates the carbachol-evoked Ca entry. The isoflurane sensitive Ca entry involves a cationic channel different from the L- or N- type voltage-dependent Ca channels. These results indicate that isoflurane attenuates the carbachol-evoked [Ca]cyt transient at a site at the plasma membrane that is distal to the muscarinic receptor.

  13. MicroRNA-34a regulation of endothelial senescence

    Energy Technology Data Exchange (ETDEWEB)

    Ito, Takashi; Yagi, Shusuke [Department of Medicine, Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, West Henrietta, NY 14586 (United States); Yamakuchi, Munekazu, E-mail: munekazu_yamakuchi@urmc.rochester.edu [Department of Medicine, Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, West Henrietta, NY 14586 (United States)

    2010-08-06

    Research highlights: {yields} MicroRNA-34a (miR-34a) regulates senescence and cell cycle progression in endothelial cells. {yields} MiR-34a expression increases during endothelial cell senescence and in older mice. {yields} SIRT1 is a miR-34a target gene in endothelial cells. {yields} SIRT1 mediates the effects of miR-34a upon cell senescence in endothelial cells. -- Abstract: Endothelial senescence is thought to play a role in cardiovascular diseases such as atherosclerosis. We hypothesized that endothelial microRNAs (miRNAs) regulate endothelial survival and senescence. We found that miR-34a is highly expressed in primary endothelial cells. We observed that miR-34a expression increases in senescent human umbilical cord vein endothelial cells (HUVEC) and in heart and spleen of older mice. MiR-34a over-expression induces endothelial cell senescence and also suppresses cell proliferation by inhibiting cell cycle progression. Searching for how miR-34a affects senescence, we discovered that SIRT1 is a target of miR-34a. Over-expressing miR-34a inhibits SIRT1 protein expression, and knocking down miR-34a enhances SIRT1 expression. MiR-34a triggers endothelial senescence in part through SIRT1, since forced expression of SIRT1 blocks the ability of miR-34a to induce senescence. Our data suggest that miR-34a contributes to endothelial senescence through suppression of SIRT1.

  14. Strategies to reverse endothelial dysfunction in diabetic nephropathy

    OpenAIRE

    Badal, Shawn S.; Danesh, Farhad R.

    2012-01-01

    Endothelial dysfunction underlies the basic pathophysiology of microvascular complications of diabetes. Endothelial dysfunction is associated with impaired nitric oxide (NO) availability. Since NO production is tightly regulated by endothelial nitric oxide synthase (eNOS), several therapeutic strategies have been investigated and proposed to improve eNOS bioavailability in the vasculature. The findings of Cheng et al. suggest that increased availability of eNOS may be an effective strategy in...

  15. Endothelial progenitor cells, cardiovascular risk factors and lifestyle modifications.

    Science.gov (United States)

    Di Stefano, Rossella; Felice, Francesca; Feriani, Roberto; Balbarini, Alberto

    2013-04-01

    Endothelial progenitor cells (EPCs) contribute substantially to preservation of a structurally and functionally intact endothelium. EPCs home in to the sites of endothelial injury and ischemia, where they proliferate, differentiate and integrate into the endothelial layer or exert a paracrine function by producing vascular growth factors. This review will focus on successful lifestyle interventions that aim to maintain vascular health through beneficial actions on cell populations with vasculogenic potential. The results of the studies proving the role of healthy lifestyle are particularly emphasized.

  16. Endothelial Cell Implantation and Survival within Experimental Gliomas

    Science.gov (United States)

    Lal, Bachchu; Indurti, Ravi R.; Couraud, Pierre-Olivier; Goldstein, Gary W.; Laterra, John

    1994-10-01

    The delivery of therapeutic genes to primary brain neoplasms opens new opportunities for treating these frequently fatal tumors. Efficient gene delivery to tissues remains an important obstacle to therapy, and this problem has unique characteristics in brain tumors due to the blood-brain and blood-tumor barriers. The presence of endothelial mitogens and vessel proliferation within solid tumors suggests that genetically modified endothelial cells might efficiently transplant to brain tumors. Rat brain endothelial cells immortalized with the adenovirus E1A gene and further modified to express the β-galactosidase reporter were examined for their ability to survive implantation to experimental rat gliomas. Rats received 9L, F98, or C6 glioma cells in combination with endothelial cells intracranially to caudate/putamen or subcutaneously to flank. Implanted endothelial cells were identified by β-galactosidase histochemistry or by polymerase chain reaction in all tumors up to 35 days postimplantation, the latest time examined. Implanted endothelial cells appeared to cooperate in tumor vessel formation and expressed the brain-specific endothelial glucose transporter type 1 as identified by immunohistochemistry. The proliferation of implanted endothelial cells was supported by their increased number within tumors between postimplantation days 14 and 21 (P = 0.015) and by their expression of the proliferation antigen Ki67. These findings establish that genetically modified endothelial cells can be stably engrafted to growing gliomas and suggest that endothelial cell implantation may provide a means of delivering therapeutic genes to brain neoplasms and other solid tumors. In addition, endothelial implantation to brain may be useful for defining mechanisms of brain-specific endothelial differentiation.

  17. Multiple roles of protein kinase a in arachidonic acid-mediated Ca2+ entry and tumor-derived human endothelial cell migration.

    Science.gov (United States)

    Fiorio Pla, Alessandra; Genova, Tullio; Pupo, Emanuela; Tomatis, Cristiana; Genazzani, Armando; Zaninetti, Roberta; Munaron, Luca

    2010-11-01

    We recently showed that arachidonic acid (AA) triggers calcium signals in endothelial cells derived from human breast carcinoma (B-TEC). In particular, AA-dependent Ca(2+) entry is involved in the early steps of tumor angiogenesis in vitro. Here, we investigated the multiple roles of the nitric oxide (NO) and cyclic AMP/protein kinase A (PKA) pathways in AA-mediated Ca(2+) signaling in the same cells. B-TEC stimulation with 5 μmol/L AA resulted in endothelial NO synthase (NOS) phosphorylation at Ser(1177), and NO release was measured with the fluorescent NO-sensitive probe DAR4M-AM. PKA inhibition by the use of the membrane-permeable PKA inhibitory peptide myristoylated PKI(14-22) completely prevented both AA- and NO-induced calcium entry and abolished B-TEC migration promoted by AA. AA-dependent calcium entry and cell migration were significantly affected by both the NOS inhibitor N(G)-nitro-l-arginine methyl ester and the NO scavenger 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide, suggesting that NO release is functionally involved in the signaling dependent on AA. Moreover, pretreatment with carboxyamidotriazole, an antiangiogenic compound that interferes with agonist-activated calcium entry, prevented AA-dependent B-TEC motility. Interestingly, even in the absence of AA, enhancement of the cyclic AMP/PKA pathway with the adenylyl cyclase activator forskolin evoked a calcium entry dependent on NOS recruitment and NO release. The functional relevance of AA-induced calcium entry could be restricted to tumor-derived endothelial cells (EC) because AA evoked a smaller calcium entry in normal human microvascular ECs compared with B-TECs, and even more importantly, it was unable to promote cell motility in wound healing assay. This evidence opens an intriguing opportunity for differential pharmacologic treatment between normal and tumor-derived human ECs. ©2010 AACR.

  18. Downregulation of Endothelial Transient Receptor Potential Vanilloid Type 4 Channel and Small-Conductance of Ca2+-Activated K+ Channels Underpins Impaired Endothelium-Dependent Hyperpolarization in Hypertension.

    Science.gov (United States)

    Seki, Takunori; Goto, Kenichi; Kiyohara, Kanako; Kansui, Yasuo; Murakami, Noboru; Haga, Yoshie; Ohtsubo, Toshio; Matsumura, Kiyoshi; Kitazono, Takanari

    2017-01-01

    Endothelium-dependent hyperpolarization (EDH)-mediated responses are impaired in hypertension, but the underlying mechanisms have not yet been determined. The activation of small- and intermediate-conductance of Ca2+-activated K+ channels (SKCa and IKCa) underpins EDH-mediated responses. It was recently reported that Ca2+ influx through endothelial transient receptor potential vanilloid type 4 channel (TRPV4) is a prerequisite for the activation of SKCa/IKCa in endothelial cells in specific beds. Here, we attempted to determine whether the impairment of EDH in hypertension is attributable to the dysfunction of TRPV4 and S/IKCa, using isolated superior mesenteric arteries of 20-week-old stroke-prone spontaneously hypertensive rats (SHRSP) and age-matched Wistar-Kyoto (WKY) rats. In the WKY arteries, EDH-mediated responses were reduced by a combination of SKCa/IKCa blockers (apamin plus TRAM-34; 1-[(2-chlorophenyl)diphenylmethl]-1H-pyrazole) and by the blockade of TRPV4 with the selective antagonist RN-1734 or HC-067047. In the SHRSP arteries, EDH-mediated hyperpolarization and relaxation were significantly impaired when compared with WKY. GSK1016790A, a selective TRPV4 activator, evoked robust hyperpolarization and relaxation in WKY arteries. In contrast, in SHRSP arteries, the GSK1016790A-evoked hyperpolarization was small and relaxation was absent. Hyperpolarization and relaxation to cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine, a selective SKCa activator, were marginally decreased in SHRSP arteries compared with WKY arteries. The expression of endothelial TRPV4 and SKCa protein was significantly decreased in the SHRSP mesenteric arteries compared with those of WKY, whereas function and expression of IKCa were preserved in SHRSP arteries. These findings suggest that EDH-mediated responses are impaired in superior mesenteric arteries of SHRSP because of a reduction in both TRPV4 and SKCa input to EDH. © 2016 American Heart Association

  19. Syncytin is involved in breast cancer-endothelial cell fusions

    DEFF Research Database (Denmark)

    Bjerregaard, B; Holck, Susanne; Christensen, Ib Jarle

    2006-01-01

    Cancer cells can fuse spontaneously with normal host cells, including endothelial cells, and such fusions may strongly modulate the biological behaviour of tumors. However, the underlying mechanisms are unknown. We now show that human breast cancer cell lines and 63 out of 165 (38%) breast cancer...... and inhibits fusions between breast cancer cells and endothelial cells. Moreover, a syncytin inhibitory peptide also inhibits fusions between cancer and endothelial cells. These results are the first to show that syncytin is expressed by human cancer cells and is involved in cancer-endothelial cell fusions....

  20. Femtosecond-laser-assisted Descemet's stripping endothelial keratoplasty.

    Science.gov (United States)

    Cheng, Yanny Y Y; Pels, Elisabeth; Nuijts, Rudy M M A

    2007-01-01

    To our knowledge, we describe the first patient with pseudophakic bullous keratoplasty treated with femtosecond-laser-assisted endothelial keratoplasty. A 5.5 mm corneoscleral tunnel incision was made; after Descemet's membrane was stripped, an 8.0 mm posterior lamellar corneal disk prepared with a femtosecond laser was inserted into the anterior chamber against the recipient cornea without the use of corneal sutures. Four months postoperatively, the posterior corneal disk was clear and the induced astigmatism was 2.1 diopters, demonstrating a functional corneal endothelial layer. The femtosecond laser offers a new surgical approach for minimally invasive endothelial keratoplasty in corneal endothelial disorders.

  1. Vascular Endothelial Growth Factor Levels in Patients with Hypothyroidism

    Directory of Open Access Journals (Sweden)

    O.M. Didushko

    2016-01-01

    Full Text Available The objective of the investigation was to determine the levels of vascular endothelial growth factor in patients with primary hypothyroidism. Having examined 133 patients with manifested hypothyroidism, we discovered that levels of vascular endothelial growth factor significantly increased in blood plasma of both obese and non-obese patients, but the highest indices have been found in patients with hypothyroidism resulting from autoimmune thyroiditis and with obesity. The obtained correlations indicate mutually aggravating effect of thyroid hypofunction, obesity and hypercholesterolemia on the development of endothelial dysfunction in patients with primary hypothyroidism, in particular on the increase of vascular endothelial growth factor levels.

  2. High Calcium Bioglass Enhances Differentiation and Survival of Endothelial Progenitor Cells, Inducing Early Vascularization in Critical Size Bone Defects

    Science.gov (United States)

    Nguyen Ngoc, Christina; Meier, Simon; Nau, Christoph; Schaible, Alexander; Marzi, Ingo; Henrich, Dirk

    2013-01-01

    Early vascularization is a prerequisite for successful bone healing and endothelial progenitor cells (EPC), seeded on appropriate biomaterials, can improve vascularization. The type of biomaterial influences EPC function with bioglass evoking a vascularizing response. In this study the influence of a composite biomaterial based on polylactic acid (PLA) and either 20 or 40% bioglass, BG20 and BG40, respectively, on the differentiation and survival of EPCs in vitro was investigated. Subsequently, the effect of the composite material on early vascularization in a rat calvarial critical size defect model with or without EPCs was evaluated. Human EPCs were cultured with β-TCP, PLA, BG20 or BG40, and seeding efficacy, cell viability, cell morphology and apoptosis were analysed in vitro. BG40 released the most calcium, and improved endothelial differentiation and vitality best. This effect was mimicked by adding an equivalent amount of calcium to the medium and was diminished in the presence of the calcium chelator, EGTA. To analyze the effect of BG40 and EPCs in vivo, a 6-mm diameter critical size calvarial defect was created in rats (n = 12). Controls (n = 6) received BG40 and the treatment group (n = 6) received BG40 seeded with 5×105 rat EPCs. Vascularization after 1 week was significantly improved when EPCs were seeded onto BG40, compared to implanting BG40 alone. This indicates that Ca2+ release improves EPC differentiation and is useful for enhanced early vascularization in critical size bone defects. PMID:24244419

  3. Gene Therapy by Targeted Adenovirus-mediated Knockdown of Pulmonary Endothelial Tph1 Attenuates Hypoxia-induced Pulmonary Hypertension

    Science.gov (United States)

    Morecroft, Ian; White, Katie; Caruso, Paola; Nilsen, Margaret; Loughlin, Lynn; Alba, Raul; Reynolds, Paul N; Danilov, Sergei M; Baker, Andrew H; MacLean, Margaret R

    2012-01-01

    Serotonin is produced by pulmonary arterial endothelial cells (PAEC) via tryptophan hydroxylase-1 (Tph1). Pathologically, serotonin acts on underlying pulmonary arterial cells, contributing to vascular remodeling associated with pulmonary arterial hypertension (PAH). The effects of hypoxia on PAEC-Tph1 activity are unknown. We investigated the potential of a gene therapy approach to PAH using selective inhibition of PAEC-Tph1 in vivo in a hypoxic model of PAH. We exposed cultured bovine pulmonary arterial smooth muscle cells (bPASMCs) to conditioned media from human PAECs (hPAECs) before and after hypoxic exposure. Serotonin levels were increased in hypoxic PAEC media. Conditioned media evoked bPASMC proliferation, which was greater with hypoxic PAEC media, via a serotonin-dependent mechanism. In vivo, adenoviral vectors targeted to PAECs (utilizing bispecific antibody to angiotensin-converting enzyme (ACE) as the selective targeting system) were used to deliver small hairpin Tph1 RNA sequences in rats. Hypoxic rats developed PAH and increased lung Tph1. PAEC-Tph1 expression and development of PAH were attenuated by our PAEC-Tph1 gene knockdown strategy. These results demonstrate that hypoxia induces Tph1 activity and selective knockdown of PAEC-Tph1 attenuates hypoxia-induced PAH in rats. Further investigation of pulmonary endothelial-specific Tph1 inhibition via gene interventions is warranted. PMID:22525513

  4. Complexin Mutants Reveal Partial Segregation between Recycling Pathways That Drive Evoked and Spontaneous Neurotransmission

    Science.gov (United States)

    Sabeva, Nadezhda; Cho, Richard W.; Vasin, Alexander; Gonzalez, Agustin; Littleton, J. Troy

    2017-01-01

    Synaptic vesicles fuse at morphological specializations in the presynaptic terminal termed active zones (AZs). Vesicle fusion can occur spontaneously or in response to an action potential. Following fusion, vesicles are retrieved and recycled within nerve terminals. It is still unclear whether vesicles that fuse spontaneously or following evoked release share similar recycling mechanisms. Genetic deletion of the SNARE-binding protein complexin dramatically increases spontaneous fusion, with the protein serving as the synaptic vesicle fusion clamp at Drosophila synapses. We examined synaptic vesicle recycling pathways at complexin null neuromuscular junctions, where spontaneous release is dramatically enhanced. We combined loading of the lipophilic dye FM1–43 with photoconversion, electron microscopy, and electrophysiology to monitor evoked and spontaneous recycling vesicle pools. We found that the total number of recycling vesicles was equal to those retrieved through spontaneous and evoked pools, suggesting that retrieval following fusion is partially segregated for spontaneous and evoked release. In addition, the kinetics of FM1–43 destaining and synaptic depression measured in the presence of the vesicle-refilling blocker bafilomycin indicated that spontaneous and evoked recycling pools partially intermix during the release process. Finally, FM1–43 photoconversion combined with electron microscopy analysis indicated that spontaneous recycling preferentially involves synaptic vesicles in the vicinity of AZs, whereas vesicles recycled following evoked release involve a larger intraterminal pool. Together, these results suggest that spontaneous and evoked vesicles use separable recycling pathways and then partially intermix during subsequent rounds of fusion. SIGNIFICANCE STATEMENT Neurotransmitter release involves fusion of synaptic vesicles with the plasma membrane in response to an action potential, or spontaneously in the absence of stimulation. Upon

  5. Characterization of the time course of changes of the evoked electrical activity in a model of a chemically-induced neuronal plasticity

    Directory of Open Access Journals (Sweden)

    Ruaro Maria

    2009-01-01

    Full Text Available Abstract Background Neuronal plasticity is initiated by transient elevations of neuronal networks activity leading to changes of synaptic properties and providing the basis for memory and learning 1. An increase of electrical activity can be caused by electrical stimulation 2 or by pharmacological manipulations: elevation of extracellular K+ 3, blockage of inhibitory pathways 4 or by an increase of second messengers intracellular concentrations 5. Neuronal plasticity is mediated by several biochemical pathways leading to the modulation of synaptic strength, density of ionic channels and morphological changes of neuronal arborisation 6. On a time scale of a few minutes, neuronal plasticity is mediated by local protein trafficking 7 while, in order to sustain modifications beyond 2–3 h, changes of gene expression are required 8. Findings In the present manuscript we analysed the time course of changes of the evoked electrical activity during neuronal plasticity and we correlated it with a transcriptional analysis of the underlying changes of gene expression. Our investigation shows that treatment for 30 min. with the GABAA receptor antagonist gabazine (GabT causes a potentiation of the evoked electrical activity occurring 2–4 hours after GabT and the concomitant up-regulation of 342 genes. Inhibition of the ERK1/2 pathway reduced but did not abolish the potentiation of the evoked response caused by GabT. In fact not all the genes analysed were blocked by ERK1/2 inhibitors. Conclusion These results are in agreement with the notion that neuronal plasticity is mediated by several distinct pathways working in unison.

  6. Differential effect of ketamine and lidocaine on spontaneous and mechanical evoked pain in patients with nerve injury pain

    DEFF Research Database (Denmark)

    Gottrup, Hanne; Bach, Flemming Winther; Juhl, Gitte Irene

    2006-01-01

    ketamine, an N-methyl-D-aspartate receptor antagonist and lidocaine, a sodium channel blocker, on spontaneous pain, brush-evoked pain, and pinprick-evoked pain in patients with nerve injury pain. METHODS: Twenty patients participated in two randomized, double-blinded, placebo-controlled, crossover...... experiments in which they, on four different days, received a 30-minute intravenous infusion of ketamine (0.24 mg/kg), lidocaine (5 mg/kg), or saline. Ongoing pain, pain evoked by brush and repetitive pinprick stimuli, and acetone was measured before, during, and after infusion. RESULTS: Ketamine...... significantly reduced ongoing pain and evoked pain to brush and pinprick, whereas lidocaine only reduced evoked pain to repetitive pinprick stimuli. In individual patients, there was no correlation between the pain-relieving effect of lidocaine and ketamine on ongoing or mechanically evoked pains. CONCLUSIONS...

  7. Pattern-reversal visual evoked potentials as a diagnostic tool for ocular malingering

    Directory of Open Access Journals (Sweden)

    Tarciana de Souza Soares

    Full Text Available ABSTRACT Purpose: To investigate the contributions of transient pattern-reversal visual evoked potentials in the diagnosis of ocular malingering at a Brazilian university hospital. Methods: Adult patients with suspected malingering in one or both eyes were referred for visual evoked potential testing. Data from patients' medical records were reviewed and analyzed retrospectively. Data analysis included the distance optotype visual acuity based on a ETDRS retro-illuminated chart and the transient pattern-reversal visual evoked potential parameters of latency (milliseconds and amplitude (microvolts for the P100 component, using checkerboards with visual subtenses of 15' and 60'. Motivations for malingering were noted. Results: The 20 subjects included 11 (55% women. Patient ages ranged from 21 to 61 years (mean= 45.05 ± 11.76 years; median= 49 years. In 8 patients (6 women, both eyes exhibited reduced visual acuity with normal pattern-reversal visually evoked potential parameters (pure malingerers. The remaining 12 patients (7 men exhibited reduced vision in only 1 eye, with simulated reduced vision in the contralateral eye (exaggerators. Financial motivation was noted in 18 patients (9 men. Conclusion: Normal pattern-reversal visually evoked potential parameters with suspected ocular malingering were observed in a 20 patient cohort. This electrophysiological technique appeared to be useful as a measure of visual pathway integrity in this specific population.

  8. From Nose to Memory: The Involuntary Nature of Odor-evoked Autobiographical Memories in Alzheimer's Disease.

    Science.gov (United States)

    El Haj, Mohamad; Gandolphe, Marie Charlotte; Gallouj, Karim; Kapogiannis, Dimitrios; Antoine, Pascal

    2017-12-25

    Research suggests that odors may serve as a potent cue for autobiographical retrieval. We tested this hypothesis in Alzheimer's disease (AD) and investigated whether odor-evoked autobiographical memory is an involuntary process that shares similarities with music-evoked autobiographical memory. Participants with mild AD and controls were asked to retrieve 2 personal memories after odor exposure, after music exposure, and in an odor-and music-free condition. AD participants showed better specificity, emotional experience, mental time travel, and retrieval time after odor and music exposure than in the control condition. Similar beneficial effects of odor and music exposure were observed for autobiographical characteristics (i.e., specificity, emotional experience, and mental time travel), except for retrieval time which was more improved after odor than after music exposure. Interestingly, regression analyses suggested executive involvement in memories evoked in the control condition but not in those evoked after music or odor exposure. These findings suggest the involuntary nature of odor-evoked autobiographical memory in AD. They also suggest that olfactory cuing could serve as a useful and ecologically valid tool to stimulate autobiographical memory, at least in the mild stage of the disease. © The Author(s) 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. Reduction hybrid artifacts of EMG-EOG in electroencephalography evoked by prefrontal transcranial magnetic stimulation

    Science.gov (United States)

    Bai, Yang; Wan, Xiaohong; Zeng, Ke; Ni, Yinmei; Qiu, Lirong; Li, Xiaoli

    2016-12-01

    Objective. When prefrontal-transcranial magnetic stimulation (p-TMS) performed, it may evoke hybrid artifact mixed with muscle activity and blink activity in EEG recordings. Reducing this kind of hybrid artifact challenges the traditional preprocessing methods. We aim to explore method for the p-TMS evoked hybrid artifact removal. Approach. We propose a novel method used as independent component analysis (ICA) post processing to reduce the p-TMS evoked hybrid artifact. Ensemble empirical mode decomposition (EEMD) was used to decompose signal into multi-components, then the components were separated with artifact reduced by blind source separation (BSS) method. Three standard BSS methods, ICA, independent vector analysis, and canonical correlation analysis (CCA) were tested. Main results. Synthetic results showed that EEMD-CCA outperformed others as ICA post processing step in hybrid artifacts reduction. Its superiority was clearer when signal to noise ratio (SNR) was lower. In application to real experiment, SNR can be significantly increased and the p-TMS evoked potential could be recovered from hybrid artifact contaminated signal. Our proposed method can effectively reduce the p-TMS evoked hybrid artifacts. Significance. Our proposed method may facilitate future prefrontal TMS-EEG researches.

  10. Cortical Auditory-Evoked Responses in Preterm Neonates: Revisited by Spectral and Temporal Analyses.

    Science.gov (United States)

    Kaminska, A; Delattre, V; Laschet, J; Dubois, J; Labidurie, M; Duval, A; Manresa, A; Magny, J-F; Hovhannisyan, S; Mokhtari, M; Ouss, L; Boissel, A; Hertz-Pannier, L; Sintsov, M; Minlebaev, M; Khazipov, R; Chiron, C

    2017-08-11

    Characteristic preterm EEG patterns of "Delta-brushes" (DBs) have been reported in the temporal cortex following auditory stimuli, but their spatio-temporal dynamics remains elusive. Using 32-electrode EEG recordings and co-registration of electrodes' position to 3D-MRI of age-matched neonates, we explored the cortical auditory-evoked responses (AERs) after 'click' stimuli in 30 healthy neonates aged 30-38 post-menstrual weeks (PMW). (1) We visually identified auditory-evoked DBs within AERs in all the babies between 30 and 33 PMW and a decreasing response rate afterwards. (2) The AERs showed an increase in EEG power from delta to gamma frequency bands over the middle and posterior temporal regions with higher values in quiet sleep and on the right. (3) Time-frequency and averaging analyses showed that the delta component of DBs, which negatively peaked around 550 and 750 ms over the middle and posterior temporal regions, respectively, was superimposed with fast (alpha-gamma) oscillations and corresponded to the late part of the cortical auditory-evoked potential (CAEP), a feature missed when using classical CAEP processing. As evoked DBs rate and AERs delta to alpha frequency power decreased until full term, auditory-evoked DBs are thus associated with the prenatal development of auditory processing and may suggest an early emerging hemispheric specialization. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  11. Electrically-evoked frequency-following response (EFFR) in the auditory brainstem of guinea pigs.

    Science.gov (United States)

    He, Wenxin; Ding, Xiuyong; Zhang, Ruxiang; Chen, Jing; Zhang, Daoxing; Wu, Xihong

    2014-01-01

    It is still a difficult clinical issue to decide whether a patient is a suitable candidate for a cochlear implant and to plan postoperative rehabilitation, especially for some special cases, such as auditory neuropathy. A partial solution to these problems is to preoperatively evaluate the functional integrity of the auditory neural pathways. For evaluating the strength of phase-locking of auditory neurons, which was not reflected in previous methods using electrically evoked auditory brainstem response (EABR), a new method for recording phase-locking related auditory responses to electrical stimulation, called the electrically evoked frequency-following response (EFFR), was developed and evaluated using guinea pigs. The main objective was to assess feasibility of the method by testing whether the recorded signals reflected auditory neural responses or artifacts. The results showed the following: 1) the recorded signals were evoked by neuron responses rather than by artifact; 2) responses evoked by periodic signals were significantly higher than those evoked by the white noise; 3) the latency of the responses fell in the expected range; 4) the responses decreased significantly after death of the guinea pigs; and 5) the responses decreased significantly when the animal was replaced by an electrical resistance. All of these results suggest the method was valid. Recording obtained using complex tones with a missing fundamental component and using pure tones with various frequencies were consistent with those obtained using acoustic stimulation in previous studies.

  12. Effects of single cycle binaural beat duration on auditory evoked potentials.

    Science.gov (United States)

    Mihajloski, Todor; Bohorquez, Jorge; Özdamar, Özcan

    2014-01-01

    Binaural beat (BB) illusions are experienced as continuous central pulsations when two sounds with slightly different frequencies are delivered to each ear. It has been shown that steady-state auditory evoked potentials (AEPs) to BBs can be captured and investigated. The authors recently developed a new method of evoking transient AEPs to binaural beats using frequency modulated stimuli. This methodology was able to create single BBs in predetermined intervals with varying carrier frequencies. This study examines the effects of the BB duration and the frequency modulating component of the stimulus on the binaural beats and their evoked potentials. Normal hearing subjects were tested with a set of four durations (25, 50, 100, and 200 ms) with two stimulation configurations, binaural dichotic (binaural beats) and diotic (frequency modulation). The results obtained from the study showed that out of the given durations, the 100 ms beat, was capable of evoking the largest amplitude responses. The frequency modulation effect showed a decrease in peak amplitudes with increasing beat duration until their complete disappearance at 200 ms. Even though, at 200 ms, the frequency modulation effects were not present, the binaural beats were still perceived and captured as evoked potentials.

  13. Evoked response audiometry in scrub typhus: prospective, randomised, case-control study.

    Science.gov (United States)

    Thakur, J S; Mohindroo, N K; Sharma, D R; Soni, K; Kaushal, S S

    2011-06-01

    To investigate the hypothesis of cochlear and retrocochlear damage in scrub typhus, using evoked response audiometry. Prospective, randomised, case-control study. The study included 25 patients with scrub typhus and 25 controls with other febrile illnesses not known to cause hearing loss. Controls were age- and sex-matched. All subjects underwent pure tone audiometry and evoked response audiometry before commencing treatment. Six patients presented with hearing loss, although a total of 23 patients had evidence of symmetrical high frequency loss on pure tone audiometry. Evoked response audiometry found significant prolongation of absolute latencies of wave I, III, V, and wave I-III interpeak latency. Two cases with normal hearing had increased interpeak latencies. These findings constitute level 3b evidence. Findings were suggestive of retrocochlear pathology in two cases with normal hearing. In other patients, high frequency hearing loss may have led to altered evoked response results. Although scrub typhus appears to cause middle ear cochlear and retrocochlear damage, the presence of such damage could not be fully confirmed by evoked response audiometry.

  14. Speech-evoked auditory brainstem responses in children with hearing loss.

    Science.gov (United States)

    Koravand, Amineh; Al Osman, Rida; Rivest, Véronique; Poulin, Catherine

    2017-08-01

    The main objective of the present study was to investigate subcortical auditory processing in children with sensorineural hearing loss. Auditory Brainstem Responses (ABRs) were recorded using click and speech/da/stimuli. Twenty-five children, aged 6-14 years old, participated in the study: 13 with normal hearing acuity and 12 with sensorineural hearing loss. No significant differences were observed for the click-evoked ABRs between normal hearing and hearing-impaired groups. For the speech-evoked ABRs, no significant differences were found for the latencies of the following responses between the two groups: onset (V and A), transition (C), one of the steady-state wave (F), and offset (O). However, the latency of the steady-state waves (D and E) was significantly longer for the hearing-impaired compared to the normal hearing group. Furthermore, the amplitude of the offset wave O and of the envelope frequency response (EFR) of the speech-evoked ABRs was significantly larger for the hearing-impaired compared to the normal hearing group. Results obtained from the speech-evoked ABRs suggest that children with a mild to moderately-severe sensorineural hearing loss have a specific pattern of subcortical auditory processing. Our results show differences for the speech-evoked ABRs in normal hearing children compared to hearing-impaired children. These results add to the body of the literature on how children with hearing loss process speech at the brainstem level. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Do puzzle pieces and autism puzzle piece logos evoke negative associations?

    Science.gov (United States)

    Gernsbacher, Morton Ann; Raimond, Adam R; Stevenson, Jennifer L; Boston, Jilana S; Harp, Bev

    2017-08-01

    Puzzle pieces have become ubiquitous symbols for autism. However, puzzle-piece imagery stirs debate between those who support and those who object to its use because they believe puzzle-piece imagery evokes negative associations. Our study empirically investigated whether puzzle pieces evoke negative associations in the general public. Participants' ( N = 400) implicit negative associations were measured with an Implicit Association Task, which is a speeded categorization task, and participants' explicit associations were measured with an Explicit Association Task, which is a standard task for assessing consumers' explicit associations with brands (and images of those brands). Puzzle pieces, both those used as autism logos and those used more generically, evoked negative implicit associations ( t(399) = -5.357, p associations ( z = 4.693, p associated puzzle pieces, even generic puzzle pieces, with incompleteness, imperfection, and oddity. Our results bear public policy implications. If an organization's intention for using puzzle-piece imagery is to evoke negative associations, our results suggest the organization's use of puzzle-piece imagery is apt. However, if the organization's intention is to evoke positive associations, our results suggest that puzzle-piece imagery should probably be avoided.

  16. Relative efficacy of transcranial motor evoked potentials, mechanically-elicited electromyography, and evoked EMG to assess nerve root function during sustained retraction in a porcine model.

    Science.gov (United States)

    Lyon, Russ; Lieberman, Jeremy A; Feiner, John; Burch, Shane

    2009-07-15

    This is an animal experiment using transcranial motor evoked potentials (TcMEP), mechanically elicited electromyography (EMG), and evoked EMG during spinal nerve root retraction in a pig model. To compare the sensitivity of these 3 electrophysiological measures for a constant retraction force applied to an isolated lumbar nerve root for a specific duration of time. The incidence of nerve root injury during lumbar spine surgery ranges from 0.2% to 31%. Direct retraction of spinal nerve roots may cause these injuries, but the amount and duration of force that may safely be applied is not clear. Using an established porcine model, we examined the changes occurring to multimyotomal TcMEPs, mechanically elicited EMGs, and evoked EMGs during continuous retraction of a nerve root at a constant force applied over 10 minutes. TcMEP, mechanically elicited EMG, and evoked EMG responses were recorded from the tibialis anterior (TA) muscle in 10 experiments. The dominant root innervating the TA was determined with evoked EMG; preretraction TcMEP and nerve root stimulation threshold (NRT) was obtained. The dominant root was retracted at 2 Newton (N) for 10 minutes. TcMEP trials were elicited every minute during retraction. NRT was measured immediately after retraction. TcMEP and NRT were measured after 10 minutes of recovery. RESULTS.: During the 10 minutes of retraction at 2 N, the amplitude of the TA muscle progressively decreased in all trials in a highly significant curvilinear fashion. The mean TcMEP amplitude decreased 59% +/- 14% from baseline values. The mean NRT after 10 minutes of retraction at 2 N rose to 1.8 +/- 0.7 mA (P EMG activity was variable; tonic EMG was observed in only 2 nerve roots (20%). Three electrophysiologic methods were used intraoperatively to assess neural function during retraction of a single nerve root. Retraction produced consistent changes in TcMEPs and evoked EMG. These 2 methods show promise for assessing the limits on the force and duration

  17. Dysfunction in the fellow eyes of strabismic and anisometropic amblyopic children assessed by visually evoked potentials

    Directory of Open Access Journals (Sweden)

    Eric Pinheiro Andrade

    Full Text Available ABSTRACT Purpose: To evaluate visual acuity and transient pattern reversal (PR visual evoked potentials (VEPs in the fellow eyes of children with strabismic and/or anisometropic amblyopia. Methods: Children diagnosed with strabismic and/or anisometropic amblyopia were recruited for electrophysiological assessment by VEPs. Monocular grating and optotype acuity were measured using sweep-VEPs and an Early Treatment Diabetic Retinopathy Study chart, respectively. During the same visit, transient PR-VEPs of each eye were recorded using stimuli subtending with a visual angle of 60', 15', and 7.5'. Parameters of amplitude (in μV and latency (in ms were determined from VEP recordings. Results: A group of 40 strabismic and/or anisometropic amblyopic children (22 females: 55%, mean age= 8.7 ± 2.2 years, median= 8 years was examined. A control group of 19 healthy children (13 females: 68.4%, mean age= 8.2 ± 2.6 years, median= 8 years was also included. The fellow eyes of all amblyopes had significantly worse optotype acuity (p=0.021 than the control group, regardless of whether they were strabismic (p=0.040 or anisometropic (p=0.048. Overall, grating acuity was significantly worse in the fellow eyes of amblyopes (p=0.016 than in healthy controls. Statistically prolonged latency for visual angles of 15' and 7.5' (p=0.018 and 0.002, respectively was found in the strabismic group when compared with the control group. For the smaller visual stimulus (7.5', statistically prolonged latency was found among all fellow eyes of amblyopic children (p<0.001. Conclusions: The fellow eyes of amblyopic children showed worse optotype and grating acuity, with subtle abnormalities in the PR-VEP detected as prolonged latencies for smaller size stimuli when compared with eyes of healthy children. These findings show the deleterious effects of amblyopia in several distinct visual functions, mainly those related to spatial vision.

  18. Endothelial cell preservation at hypothermic to normothermic conditions using clinical and experimental organ preservation solutions

    NARCIS (Netherlands)

    Post, Ivo C. J. H.; de Boon, Wadim M. I.; Heger, Michal; van Wijk, Albert C. W. A.; Kroon, Jeffrey; van Buul, Jaap D.; van Gulik, Thomas M.

    2013-01-01

    Endothelial barrier function is pivotal for the outcome of organ transplantation. Since hypothermic preservation (gold standard) is associated with cold-induced endothelial damage, endothelial barrier function may benefit from organ preservation at warmer temperatures. We therefore assessed

  19. The endothelial surface layer: a new target of research in kidney failure and peritoneal dialysis

    NARCIS (Netherlands)

    Vlahu, C.A.

    2016-01-01

    The endothelial glycocalyx is an important regulator of vascular homeostasis, and damage to this complex structure results in increased vascular vulnerability. Together with associated plasma molecules it forms the endothelial surface layer. Because of its vasculoprotective effects, the endothelial

  20. The phenotype of the human materno-fetal endothelial barrier: molecular occupancy of paracellular junctions dictate permeability and angiogenic plasticity.

    Science.gov (United States)

    Leach, Lopa

    2002-06-01

    In vitro models predict that molecular occupancy of endothelial junctions may regulate both barrier function and angiogenesis. Whether this is true in human vascular beds undergoing physiological angiogenesis has not been shown. This review presents data which demonstrate there are two distinct junctional phenotypes, 'activated' and 'stable', present in the vascular tree of the human placenta taken from two distinct highly angiogenic gestational periods (first and last trimester). Stability is conferred by the presence of occludin in tight junctions and plakoglobin in adherens junctions. Their localization may be influenced by vascular endothelial growth factor and angiopoietins 1 and 2 that have a similar temporal and site-specific differential expression. The junctional phenotypes are reversible, as shown in studies with endothelial cells isolated from placental microvessels and grown in the presence/absence of cAMP-enhancing agents. Reductions in protein levels and loss of junctional localization of adhesion molecules result in increased permeability to macromolecules, whilst up-regulation and re-targeting of these molecules inhibit cell proliferation and increase transendothelial resistance. These studies suggest junctional adhesion molecules can regulate physiological angiogenesis and vascular re-modelling. Moreover, the activated junctional phenotype of placental microvessels allows them to participate in increased growth and proliferation. This junctional immaturity appears to be at the expense of barrier function resulting in sites of maximal materno-fetal solute exchange.

  1. Endothelial glycocalyx on brain endothelial cells is lost in experimental cerebral malaria

    DEFF Research Database (Denmark)

    Hempel, Casper; Hyttel, Poul; Kurtzhals, Jørgen Al

    2014-01-01

    electron microscopy and measured circulating glycosaminoglycans by dot blot and ELISA. The glycocalyx was degraded in brain vasculature in cerebral and to a lesser degree uncomplicated malaria. It was affected on both intact and apoptotic endothelial cells. Circulating glycosaminoglycan levels suggested...

  2. Human liver endothelial cells, but not macrovascular or microvascular endothelial cells, engraft in the mouse liver

    NARCIS (Netherlands)

    Filali, Ebtisam El; Hiralall, Johan K.; van Veen, Henk A.; Stolz, Donna B.; Seppen, Jurgen

    2013-01-01

    Liver cell transplantation has had limited clinical success so far, partly due to poor engraftment of hepatocytes. Instead of hepatocytes. other cell types, such as endothelial cells, could be used in ex vivo liver gene therapy. The goal of the present study was to compare the grafting and

  3. Endothelial replacement without surface corneal incisions or sutures: topography of the deep lamellar endothelial keratoplasty procedure.

    Science.gov (United States)

    Terry, M A; Ousley, P J

    2001-01-01

    To evaluate the immediate postoperative corneal topography after the deep lamellar endothelial keratoplasty procedure. Eight eye bank eyes underwent deep lamellar endothelial keratoplasty through a 9.0-mm limbal incision replacing the central 7.0 mm of posterior stroma and endothelium through the lamellar pocket wound. Orbscan topography was performed before and after surgery, and simulated keratometry readings and central corneal diopter power were recorded. The change in astigmatism and corneal power from preoperative to postoperative readings was then determined. The net change in corneal astigmatism averaged 0.4+/-0.5 diopters (range, -0.1 to 1.1 diopters). The net change in corneal power averaged -0.2+/-0.4 diopters of flattening (range, -0.9 to +0.2 diopters). Neither the astigmatism nor the corneal power levels after this surgery were significantly different from the preoperative topography (p = 0.22 and 0.27, respectively). The deep lamellar endothelial keratoplasty procedure, with its absence of corneal surface incisions or sutures, has no significant effect on immediate postoperative corneal topography. The potential advantages of this procedure over penetrating keratoplasty in the treatment of endothelial dysfunction are considerable.

  4. Action Tendency Emotions Evoked by Memorable Breast Cancer Messages and Their Association With Prevention and Detection Behaviors

    OpenAIRE

    Smith, Sandi W.; Hamel, Lauren M; Kotowski, Michael R.; Nazione, Samantha; LaPlante, Carolyn; Atkin, Charles K.; Stohl, Cynthia; Skubisz, Christine

    2010-01-01

    Memorable messages about breast cancer sent by different sources, such as friends and family members, were analyzed for the action tendency emotions that they evoked. Negative emotions of fear, sadness, and anger, and positive emotions of hope and relief were analyzed for their associations with prevention and detection breast cancer behaviors. Messages that evoked fear were significantly more likely to be associated with detection behaviors, whereas messages that evoked relief were significa...

  5. Cyclic AMP directs inositol (1,4,5)-trisphosphate-evoked Ca2+ signalling to different intracellular Ca2+ stores

    OpenAIRE

    Tovey, Stephen C.; Taylor, Colin W.

    2013-01-01

    Cholesterol depletion reversibly abolishes carbachol-evoked Ca2+ release from inositol (1,4,5)-trisphosphate (IP3)-sensitive stores, without affecting the distribution of IP3 receptors (IP3R) or endoplasmic reticulum, IP3 formation or responses to photolysis of caged IP3. Receptors that stimulate cAMP formation do not alone evoke Ca2+ signals, but they potentiate those evoked by carbachol. We show that these potentiated signals are entirely unaffected by cholesterol depletion and that, within...

  6. Radioprotection of mouse CNS endothelial cells in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Lyubimova, N.; Coultas, P.; Martin, R. [Peter McCallum Cancer Institute, Melbourne, VIC (Australia)

    1996-12-31

    Full text: Radioprotection using the minor groove binding DNA ligand Hoechst 33342 has been demonstrated in vitro, and more recently in vivo, in mouse lung. Intravenous administration was used for the lung studies, and both endothelial and alveolar epithelial cells-showed good up-take. Radiation damage to the endothelial cell population has also been postulated as important in late developing radionecrosis of spinal cord and brain. Endothelial cell density in brain can be readily determined by a fluorescent-histochemical technique. Treatment with a monoamine oxidase inhibitor and subsequent injection with L-DOPA results in an accumulation of dopamine (DA) in CNS endothelial cells. DA is converted to a fluorophore by exposure to paraformaldehyde, and cell numbers assayed by fluorescence microscopy. Earlier studies used this technique to monitor post-irradiation changes in endothelial cell density in rodent brain and showed the loss, within 24 hours, of a sensitive subpopulation comprising about 15% of the endothelial cells. Ten minutes after intravenous injection of Hoechst 33342 (80mg/kg) the ligand is confined by its limited penetration to the endothelial cells in mouse brain. When we irradiated at this time, there was protection against early endothelial cell loss. Ablation of the sensitive subpopulation in unprotected mice takes place over a dose range of 1 to 3 Gy {gamma}-rays, but doses between 12 to 20 Gy are required in the presence of ligand. This protection equates to a very high dose modification factor of about 7 and possibly reflects a suppression of apoptosis in the sensitive endothelial subpopulation. The extent to which there is enhanced survival in the endothelial population as a whole and how the observed protection affects late CNS necrosis development has yet to be determined. However present results clearly show potential for the use of DNA-binding radioprotectors with limited penetration for investigations into the relative significance of

  7. SOCS1 prevents graft arteriosclerosis by preserving endothelial cell function.

    Science.gov (United States)

    Qin, Lingfeng; Huang, Qunhua; Zhang, Haifeng; Liu, Renjing; Tellides, George; Min, Wang; Yu, Luyang

    The aim of this study was to determine the role of suppressor of cytokine signaling 1 (SOCS1) in graft arteriosclerosis (GA). GA, the major cause of late cardiac allograft failure, is initiated by immune-mediated endothelial activation resulting in vascular inflammation and consequent neointima formation. SOCS1, a negative regulator of cytokine signaling, is highly expressed in endothelial cells (ECs) and may prevent endothelial inflammatory responses and phenotypic activation. Clinical specimens of coronary arteries with GA, with atherosclerosis, or without disease were collected for histological analysis. SOCS1 knockout or vascular endothelial SOCS1 (VESOCS1) transgenic mice were used in an aorta transplant model of GA. Mouse aortic ECs were isolated for in vitro assays. Dramatic but specific reduction of endothelial SOCS1 was observed in human GA and atherosclerosis specimens, which suggested the importance of SOCS1 in maintaining normal endothelial function. SOCS1 deletion in mice resulted in basal EC dysfunction. After transplantation, SOCS1-deficient aortic grafts augmented leukocyte recruitment and neointima formation, whereas endothelial overexpression of SOCS1 diminished arterial rejection. Induction of endothelial adhesion molecules in early stages of GA was suppressed by the VESOCS1 transgene, and this effect was confirmed in cultured aortic ECs. Moreover, VESOCS1 maintained better vascular function during GA progression. Mechanistically, endothelial SOCS1, by modulating both basal and cytokine-induced expression of the adhesion molecules platelet/endothelial cell adhesion molecule-1, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1, restrained leukocyte adhesion and transendothelial migration during inflammatory cell infiltration. SOCS1 prevents GA progression by preserving endothelial function and attenuating cytokine-induced adhesion molecule expression in vascular endothelium. Copyright © 2014 American College of Cardiology

  8. Production of soluble Neprilysin by endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Kuruppu, Sanjaya, E-mail: Sanjaya.Kuruppu@monash.edu [Department of Biochemistry and Molecular Biology, Building 77, Monash University, Wellington Rd, Clayton, Vic 3800 (Australia); Rajapakse, Niwanthi W. [Department of Physiology, Building 13F, Monash University, Wellington Rd, Clayton, Vic 3800 (Australia); Minond, Dmitriy [Torrey Pines Institute for Molecular Studies, 11350 SW Village Parkway, Port Saint Lucie, FL 34987 (United States); Smith, A. Ian [Department of Biochemistry and Molecular Biology, Building 77, Monash University, Wellington Rd, Clayton, Vic 3800 (Australia)

    2014-04-04

    Highlights: • A soluble full-length form of Neprilysin exists in media of endothelial cells. • Exosomal release is the key mechanism for the production of soluble Neprilysin. • Inhibition of ADAM-17 by specific inhibitors reduce Neprilysin release. • Exosome mediated release of Neprilysin is dependent on ADAM-17 activity. - Abstract: A non-membrane bound form of Neprilysin (NEP) with catalytic activity has the potential to cleave substrates throughout the circulation, thus leading to systemic effects of NEP. We used the endothelial cell line Ea.hy926 to identify the possible role of exosomes and A Disintegrin and Metalloprotease 17 (ADAM-17) in the production of non-membrane bound NEP. Using a bradykinin based quenched fluorescent substrate (40 μM) assay, we determined the activity of recombinant human NEP (rhNEP; 12 ng), and NEP in the media of endothelial cells (10% v/v; after 24 h incubation with cells) to be 9.35 ± 0.70 and 6.54 ± 0.41 μmols of substrate cleaved over 3 h, respectively. The presence of NEP in the media was also confirmed by Western blotting. At present there are no commercially available inhibitors specific for ADAM-17. We therefore synthesised two inhibitors TPI2155-14 and TPI2155-17, specific for ADAM-17 with IC{sub 50} values of 5.36 and 4.32 μM, respectively. Treatment of cells with TPI