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Sample records for hypertrophic stimulation increases

  1. Increased left ventricular torsion in hypertrophic cardiomyopathy mutation carriers with normal wall thickness

    Science.gov (United States)

    2011-01-01

    Background Increased left ventricular (LV) torsion has been observed in patients with manifest familial hypertrophic cardiomyopathy (HCM), and is thought to be caused by subendocardial dysfunction. We hypothesize that increased LV torsion is already present in healthy mutation carriers with normal wall thickness. Methods Seventeen carriers with an LV wall thickness subendocardial myocardial dysfunction. As similar abnormalities are observed in patients with manifest HCM, the changes in healthy carriers may be target for clinical intervention to delay or prevent the onset of hypertrophy. PMID:21219655

  2. Hypertrophic cardiomyopathy.

    Science.gov (United States)

    Santos Mateo, Juan José; Sabater Molina, María; Gimeno Blanes, Juan Ramón

    2017-11-14

    Hypertrophic cardiomyopathy is the most common inherited cardiovascular disease. It is characterized by increased ventricular wall thickness and is highly complex due to its heterogeneous clinical presentation, several phenotypes, large number of associated causal mutations and broad spectrum of complications. It is caused by mutations in sarcomeric proteins, which are identified in up to 60% of cases of the disease. Clinical manifestations of Hypertrophic Cardiomyopathy include shortness of breath, chest pain, palpitations and syncope, which are related to the onset of diastolic dysfunction, left ventricular outflow tract obstruction, ischemia, atrial fibrillation and abnormal vascular responses. It is associated with an increased risk of sudden cardiac death, heart failure and thromboembolic events. In this article, we discuss the diagnostic and therapeutic aspects of this disease. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  3. Increased left ventricular torsion in hypertrophic cardiomyopathy mutation carriers with normal wall thickness

    Directory of Open Access Journals (Sweden)

    Marcus Tim J

    2011-01-01

    Full Text Available Abstract Background Increased left ventricular (LV torsion has been observed in patients with manifest familial hypertrophic cardiomyopathy (HCM, and is thought to be caused by subendocardial dysfunction. We hypothesize that increased LV torsion is already present in healthy mutation carriers with normal wall thickness. Methods Seventeen carriers with an LV wall thickness Results LV volumes, mass and circumferential strain were comparable between groups, whereas LV ejection fraction, torsion and TECS-ratio were increased in carriers compared to controls (63 ± 3% vs. 60 ± 3%, p = 0.04, 10.1 ± 2.5° vs. 7.7 ± 1.2°, p = 0.001, and 0.52 ± 0.14°/% vs. 0.42 ± 0.10°/%, p = 0.02, respectively. Conclusions Carriers with normal wall thickness display increased LV torsion and TECS-ratio with respect to controls, which might be due to subendocardial myocardial dysfunction. As similar abnormalities are observed in patients with manifest HCM, the changes in healthy carriers may be target for clinical intervention to delay or prevent the onset of hypertrophy.

  4. Hypertrophic scar formation is associated with an increased number of epidermal Langerhans cells.

    NARCIS (Netherlands)

    Niessen, F.B.; Schalkwijk, J.; Vos, H.; Timens, W.

    2004-01-01

    The exact pathogenesis of hypertrophic scar and keloid formation is still unknown and a good therapy to prevent or treat these scars is lacking. Because immunological processes seem to be important in excessive scar formation, immunological cells and parameters were studied in a standardized breast

  5. Hypertrophic scar formation is associated with an increased number of epidermal Langerhans cells

    NARCIS (Netherlands)

    Niessen, FB; Schalkwijk, J; Vos, H; Timens, W

    The exact pathogenesis of hypertrophic scar and keloid formation is still unknown and a good therapy to prevent or treat these scars is lacking. Because immunological processes seem to be important in excessive scar formation, immunological cells and parameters were studied in a standardized breast

  6. Hypoxia inhibits hypertrophic differentiation and endochondral ossification in explanted tibiae.

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    Jeroen C H Leijten

    Full Text Available Hypertrophic differentiation of growth plate chondrocytes induces angiogenesis which alleviates hypoxia normally present in cartilage. In the current study, we aim to determine whether alleviation of hypoxia is merely a downstream effect of hypertrophic differentiation as previously described or whether alleviation of hypoxia and consequent changes in oxygen tension mediated signaling events also plays an active role in regulating the hypertrophic differentiation process itself.Fetal mouse tibiae (E17.5 explants were cultured up to 21 days under normoxic or hypoxic conditions (21% and 2.5% oxygen respectively. Tibiae were analyzed on growth kinetics, histology, gene expression and protein secretion.The oxygen level had a strong influence on the development of explanted fetal tibiae. Compared to hypoxia, normoxia increased the length of the tibiae, length of the hypertrophic zone, calcification of the cartilage and mRNA levels of hypertrophic differentiation-related genes e.g. MMP9, MMP13, RUNX2, COL10A1 and ALPL. Compared to normoxia, hypoxia increased the size of the cartilaginous epiphysis, length of the resting zone, calcification of the bone and mRNA levels of hyaline cartilage-related genes e.g. ACAN, COL2A1 and SOX9. Additionally, hypoxia enhanced the mRNA and protein expression of the secreted articular cartilage markers GREM1, FRZB and DKK1, which are able to inhibit hypertrophic differentiation.Collectively our data suggests that oxygen levels play an active role in the regulation of hypertrophic differentiation of hyaline chondrocytes. Normoxia stimulates hypertrophic differentiation evidenced by the expression of hypertrophic differentiation related genes. In contrast, hypoxia suppresses hypertrophic differentiation of chondrocytes, which might be at least partially explained by the induction of GREM1, FRZB and DKK1 expression.

  7. Increased transient receptor potential vanilloid type 1 (TRPV1) channel expression in hypertrophic heart

    DEFF Research Database (Denmark)

    Thilo, Florian; Liu, Ying; Schulz, Nico

    2010-01-01

    The aim of this study was to compare the expression of transient receptor potential vanilloid type 1 (TRPV1) channels in hypertrophic hearts from transgenic mice showing overexpression of the catalytic subunit alpha of protein phosphatase 2A alpha (PP2Ac alpha) with wild-type mice and with TRPV1......-/- mice. Transcripts of TRPV1, matrix metalloproteinase 9 (MMP9), discoidin domain receptor family, member 2 (DDR-2), atrial natriuretic peptide (ANP), GATA 4, and regulatory microRNA (miR-21) were analyzed using quantitative real-time PCR. Ventricle-to-body-weight-ratio was significantly higher in PP2Ac...

  8. Optogenetic stimulation of MCH neurons increases sleep.

    Science.gov (United States)

    Konadhode, Roda Rani; Pelluru, Dheeraj; Blanco-Centurion, Carlos; Zayachkivsky, Andrew; Liu, Meng; Uhde, Thomas; Glen, W Bailey; van den Pol, Anthony N; Mulholland, Patrick J; Shiromani, Priyattam J

    2013-06-19

    Melanin concentrating hormone (MCH) is a cyclic neuropeptide present in the hypothalamus of all vertebrates. MCH is implicated in a number of behaviors but direct evidence is lacking. To selectively stimulate the MCH neurons the gene for the light-sensitive cation channel, channelrhodopsin-2, was inserted into the MCH neurons of wild-type mice. Three weeks later MCH neurons were stimulated for 1 min every 5 min for 24 h. A 10 Hz stimulation at the start of the night hastened sleep onset, reduced length of wake bouts by 50%, increased total time in non-REM and REM sleep at night, and increased sleep intensity during the day cycle. Sleep induction at a circadian time when all of the arousal neurons are active indicates that MCH stimulation can powerfully counteract the combined wake-promoting signal of the arousal neurons. This could be potentially useful in treatment of insomnia.

  9. Faster cross-bridge detachment and increased tension cost in human hypertrophic cardiomyopathy with the R403Q MYH7 mutation

    NARCIS (Netherlands)

    E.R. Witjas-Paalberends (E. Rosalie); C. Ferrara (Claudia); B. Scellini (Beatrice); N. Piroddi (Nicoletta); J. Montag (Judith); C. Tesi (Chiara); G.J.M. Stienen (Ger); M. Michels (Michelle); C.Y. Ho (Carolyn); T. Kraft (Theresia); C. Poggesi (Corrado); J. van der Velden (Jolanda)

    2014-01-01

    textabstractThe first mutation associated with hypertrophic cardiomyopathy (HCM) is the R403Q mutation in the gene encoding β-myosin heavy chain (β-MyHC). R403Q locates in the globular head of myosin (S1), responsible for interaction with actin, and thus motor function of myosin. Increased

  10. Overexpression of M3 Muscarinic Receptor Suppressed Adverse Electrical Remodeling in Hypertrophic Myocardium Via Increasing Repolarizing K+ Currents

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    Xue Chen

    2017-09-01

    Full Text Available Background/Aims: Cardiac hypertrophy (CH is an adaptive response to diverse cardiovascular conditions, which is accompanied by adverse electrical remodeling manifested as abnormal K+ channel activities. M3 subtype of muscarinic acetylcholine receptor (M3-mAChR is a novel regulator of cardiac electrical activity. In this study we aim to explore if the overexpression of M3-mAChR could attenuate the adverse electrical remodeling in CH and then uncover its underlying electrophysiological mechanisms. Methods: Transgenic mice with M3-mAChR overexpression (M3-TG and wild type (WT mice were subjected to transverse aortic constriction (TAC to induce CH. Myocardial hypertrophy and cardiac function were quantified by the measurement of echocardiography, electrocardiogram, heart weight and tibia length. Whole-cell and signal-cell patch-clamp were employed to record electrophysiological properties by acute isolation of acutely isolated ventricular cardiomyocytes and Western blot was carried out to evaluate the Kir2.1and Kv4.2/4.3 protein levels in left ventricular tissue. Results: Compared with WT group, the elevation of cardiac index, including heart weight/body weight index and heart weight/tibia length index confirmed the myocardial hypertrophic growth induced by TAC. Echocardiography detection revealed that the TAC-treated mice showed an obvious increase in the thickness of left ventricular posterior wall (LVPW and ejection fraction (EF due to compensatory hypertrophy, which attenuated by the overexpression of M3-mAChR. Pressure overload induced a prolongation of QTc interval in WT mice, an effect blunted in M3-TG mice. Furthermore, compared with WT mice, M3-mAChR overexpression in hypertrophic myocardium accelerated cardiac repolarization and shortened action potential duration, and thus correcting the prolongation of QTc interval. Moreover, M3-TG mice have the greater current density of IK1 and Ito in ventricular myocytes after TAC compared with WT

  11. Hypertrophic cardiomyopathy.

    Science.gov (United States)

    Subasic, Kim

    2013-12-01

    Hypertrophic cardiomyopathy (HCM) is an autosomal dominant, cardiovascular disorder that carries the risk of sudden cardiac death. The prevalence of HCM is 1:500 persons. The purpose of this article is to provide an overview of the pathophysiology, symptoms, complications, diagnostic testing, and treatment. The silent presentation of HCM presents unique diagnostic challenges and complicates prompt identification. Diagnostic testing and management strategies for the care of a person with HCM are discussed. HCM has individualized presentation and therefore requires individualized therapy. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. MicroRNA 181b regulates decorin production by dermal fibroblasts and may be a potential therapy for hypertrophic scar.

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    Peter Kwan

    Full Text Available Hypertrophic scarring is a frequent fibroproliferative complication following deep dermal burns leading to impaired function and lifelong disfigurement. Decorin reduces fibrosis and induces regeneration in many tissues, and is significantly downregulated in hypertrophic scar and normal deep dermal fibroblasts. It was hypothesized that microRNAs in these fibroblasts downregulate decorin and blocking them would increase decorin and may prevent hypertrophic scarring. Lower decorin levels were found in hypertrophic scar as compared to normal skin, and in deep as compared to superficial dermis. A decorin 3' un-translated region reporter assay demonstrated microRNA decreased decorin in deep dermal fibroblasts, and microRNA screening predicted miR- 24, 181b, 421, 526b, or 543 as candidates. After finding increased levels of mir-181b in deep dermal fibroblasts, it was demonstrated that TGF-β1 stimulation decreased miR-24 but increased miR-181b and that hypertrophic scar and deep dermis contained increased levels of miR-181b. By blocking miR-181b with an antagomiR, it was possible to increase decorin protein expression in dermal fibroblasts. This suggests miR-181b is involved in the differential expression of decorin in skin and wound healing. Furthermore, blocking miR-181b reversed TGF-β1 induced decorin downregulation and myofibroblast differentiation in hypertrophic scar fibroblasts, suggesting a potential therapy for hypertrophic scar.

  13. KCl stimulation increases norepinephrine transporter function in PC12 cells.

    Science.gov (United States)

    Mandela, Prashant; Ordway, Gregory A

    2006-09-01

    The norepinephrine transporter (NET) plays a pivotal role in terminating noradrenergic signaling and conserving norepinephrine (NE) through the process of re-uptake. Recent evidence suggests a close association between NE release and regulation of NET function. The present study evaluated the relationship between release and uptake, and the cellular mechanisms that govern these processes. KCl stimulation of PC12 cells robustly increased [3H]NE uptake via the NET and simultaneously increased [3H]NE release. KCl-stimulated increases in uptake and release were dependent on Ca2+. Treatment of cells with phorbol-12-myristate-13-acetate (PMA) or okadaic acid decreased [3H]NE uptake but did not block KCl-stimulated increases in [3H]NE uptake. In contrast, PMA increased [3H]NE release and augmented KCl-stimulated release, while okadaic acid had no effects on release. Inhibition of Ca2+-activated signaling cascades with KN93 (a Ca2+ calmodulin-dependent kinase inhibitor), or ML7 and ML9 (myosin light chain kinase inhibitors), reduced [3H]NE uptake and blocked KCl-stimulated increases in uptake. In contrast, KN93, ML7 and ML9 had no effect on KCl-stimulated [3H]NE release. KCl-stimulated increases in [3H]NE uptake were independent of transporter trafficking to the plasma membrane. While increases in both NE release and uptake mediated by KCl stimulation require Ca2+, different intracellular mechanisms mediate these two events.

  14. Hypertrophic Cardiomyopathy Association

    Science.gov (United States)

    ... organization improving the lives of those with hypertrophic cardiomyopathy, HCM, preventing untimely deaths and advancing global understanding. ... item purchased, 10% will be donated to Hypertrophic Cardiomyopathy Association. iGive.com - Online Shopping Joing iGive.com ...

  15. Deep brain stimulation: increasing efficiency by alternative waveforms

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    Argiti Katerina

    2016-09-01

    Full Text Available Deep brain stimulation (DBS is based on the effect of high frequency stimulation (HFS in neuronal tissue. As a therapy option for patients suffering from e.g. Parkinson’s disease, DBS has been used for decades. Despite the widespread use, the effect of HFS on neurons is not fully investigated. Improving the stimulation efficiency und specificity could increase the efficiency of the INS (internal neuronal stimulator as well as potentially reduce unwanted side effects. The effect of HFS on the GABAergic system was quantified using whole cell patch clamp electrophysiology during HFS stimulation in cortical human brain slices in vitro. Rectangular, sine, sawtooth and triangular waveforms were applied extracellularly. Since HFS has been hypothesized to increase the activity of the axons of GABAergic interneurons, a decrease in activity can be observed in the pyramidal cells that the interneurons project to. By isolating the incoming non- GABAergic events, we can filter out only the GABAA currents which can be verified using a GABAA antagonist. The results show that all the waveforms effectively increase the GABAA currents. The triangle waveform causes the highest significant increase in the activity which further increases over time after the stimulation was turned off.

  16. Abnormal papillary muscle morphology is independently associated with increased left ventricular outflow tract obstruction in hypertrophic cardiomyopathy.

    Science.gov (United States)

    Kwon, D H; Setser, R M; Thamilarasan, M; Popovic, Z V; Smedira, N G; Schoenhagen, P; Garcia, M J; Lever, H M; Desai, M Y

    2008-10-01

    Abnormal papillary muscles (PM) are often found in hypertrophic cardiomyopathy (HCM). To assess the relationship between morphological alterations of PM in patients with HCM and left ventricular outflow tract (LVOT) obstruction, using magnetic resonance imaging (MRI) and echocardiography. Fifty-six patients with HCM (mean age 42 years (interquartile range 27, 51), 70% male) and 30 controls (mean age (42 (30, 53) years, 80% male) underwent MRI on a 1.5 T scanner (Siemens, Erlangen, Germany). Standard cine images were obtained in short-axis (base to apex), along with two-, three- and four-chamber views. The presence of bifid PM (none, one or both) and anteroapical displacement of anterolateral PM was recorded by MRI and correlated with resting LVOT gradients obtained by echocardiography. Double bifid PM (70% vs 17%) and anteroapical displacement of anterolateral PM (77% vs 17%) were more prevalent in patients with HCM than in controls (panteroapically displaced PM and double bifid PM had higher resting LVOT gradients than controls (45 (6, 81) vs 12 (0, 12) mm Hg (por=30 mm Hg) peak resting gradient was 7.1 (95% CI 1.4 to 36.7) for anteroapically displaced anterolateral PM and 10.4 (95% CI 1.2 to 91.2) for double bifid PM (both p = 0.005), independent of septal thickness, use of beta-blockers and/or calcium blockers and resting heart rate. Patients with HCM with abnormal PM have a higher degree of resting LVOT gradient, which is independent of septal thickness.

  17. In vitro analysis of SERCA2 gene regulation in hypertrophic cardiomyocytes and increasing transfection efficiency by gene-gun biolistics

    NARCIS (Netherlands)

    K. Eizema (Karin); H.A. van Heugten (Han); K. Bezstarosti (Karel); M.C. van Setten (Marga); J.M.J. Lamers (Jos)

    1999-01-01

    textabstractThe transcriptional downregulation of the SERCA2 gene is studied using neonatal rat cardiomyocytes stimulated with endothelin-1 to induce hypertrophy. Liposome-based transfection of cells with a 1.9 kb SERCA2 promoter fragment directed expression of a reporter gene identical to the

  18. Electrical stimulation to increase lower esophageal sphincter pressure after POEM.

    Science.gov (United States)

    Ciotola, Franco; Ditaranto, Andres; Bilder, Claudio; Badaloni, Adolfo; Lowenstein, Daniel; Riganti, Juan Martin; Hoppo, Toshitaka; Jobe, Blair; Nachman, Fabio; Nieponice, Alejandro

    2015-01-01

    Postoperative reflux remains to be a challenge for patients with achalasia undergoing Heller myotomy. Similarly, per-oral endoscopic myotomy (POEM) is gaining rapid acceptance but the impossibility of adding a fundoplication is questioned as the main pitfall to control reflux. Electrical stimulation of the lower esophageal sphincter (LES) has emerged as a new alternative for the treatment of reflux disease. The objective of this study was to evaluate the potential benefits of combining electrical stimulation with endoscopic esophageal myotomy to prevent post procedural reflux. Five pigs were subjected to POEM. After myotomy was completed, two electrical leads were implanted at the LES level and electrical stimulation was applied with the Endostim system with a regimen of 215 μs (5 mA amplitude), at 20 Hz for 25 min. LES pressures were recorded with manometry at pre and post-myotomy and after LES stimulation. Myotomy was completed successfully in all cases. Mean pre-myotomy LES pressure was 35.99 ± 8.08 mmHg. After myotomy, the LES pressure significantly dropped to 10.60 ± 3.24 mmHg (p = 0.03). Subsequent to LES-EST, LES pressure significantly increased to 21.74 ± 4.65 mmHg (p = 0.01). The findings of this study show that LES-EST in healthy animals increases LES pressure after POEM procedure, and could be useful tool to minimize gastroesophageal reflux.

  19. Tactile thermal oral stimulation increases the cortical representation of swallowing

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    Suntrup Sonja

    2009-06-01

    Full Text Available Abstract Background Dysphagia is a leading complication in stroke patients causing aspiration pneumonia, malnutrition and increased mortality. Current strategies of swallowing therapy involve on the one hand modification of eating behaviour or swallowing technique and on the other hand facilitation of swallowing with the use of pharyngeal sensory stimulation. Thermal tactile oral stimulation (TTOS is an established method to treat patients with neurogenic dysphagia especially if caused by sensory deficits. Little is known about the possible mechanisms by which this interventional therapy may work. We employed whole-head MEG to study changes in cortical activation during self-paced volitional swallowing in fifteen healthy subjects with and without TTOS. Data were analyzed by means of synthetic aperture magnetometry (SAM and the group analysis of individual SAM data was performed using a permutation test. Results Compared to the normal swallowing task a significantly increased bilateral cortical activation was seen after oropharyngeal stimulation. Analysis of the chronological changes during swallowing suggests facilitation of both the oral and the pharyngeal phase of deglutition. Conclusion In the present study functional cortical changes elicited by oral sensory stimulation could be demonstrated. We suggest that these results reflect short-term cortical plasticity of sensory swallowing areas. These findings facilitate our understanding of the role of cortical reorganization in dysphagia treatment and recovery.

  20. Tactile thermal oral stimulation increases the cortical representation of swallowing

    Science.gov (United States)

    Teismann, Inga K; Steinsträter, Olaf; Warnecke, Tobias; Suntrup, Sonja; Ringelstein, Erich B; Pantev, Christo; Dziewas, Rainer

    2009-01-01

    Background Dysphagia is a leading complication in stroke patients causing aspiration pneumonia, malnutrition and increased mortality. Current strategies of swallowing therapy involve on the one hand modification of eating behaviour or swallowing technique and on the other hand facilitation of swallowing with the use of pharyngeal sensory stimulation. Thermal tactile oral stimulation (TTOS) is an established method to treat patients with neurogenic dysphagia especially if caused by sensory deficits. Little is known about the possible mechanisms by which this interventional therapy may work. We employed whole-head MEG to study changes in cortical activation during self-paced volitional swallowing in fifteen healthy subjects with and without TTOS. Data were analyzed by means of synthetic aperture magnetometry (SAM) and the group analysis of individual SAM data was performed using a permutation test. Results Compared to the normal swallowing task a significantly increased bilateral cortical activation was seen after oropharyngeal stimulation. Analysis of the chronological changes during swallowing suggests facilitation of both the oral and the pharyngeal phase of deglutition. Conclusion In the present study functional cortical changes elicited by oral sensory stimulation could be demonstrated. We suggest that these results reflect short-term cortical plasticity of sensory swallowing areas. These findings facilitate our understanding of the role of cortical reorganization in dysphagia treatment and recovery. PMID:19566955

  1. Stimulation of Suicidal Erythrocyte Death by Increased Extracellular Phosphate Concentrations

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    Jakob Voelkl

    2014-02-01

    Full Text Available Background/Aim: Anemia in renal insufficiency results in part from impaired erythrocyte formation due to erythropoietin and iron deficiency. Beyond that, renal insufficiency enhances eryptosis, the suicidal erythrocyte death characterized by phosphatidylserine-exposure at the erythrocyte surface. Eryptosis may be stimulated by increase of cytosolic Ca2+-activity ([Ca2+]i. Several uremic toxins have previously been shown to stimulate eryptosis. Renal insufficiency is further paralleled by increase of plasma phosphate concentration. The present study thus explored the effect of phosphate on erythrocyte death. Methods: Cell volume was estimated from forward scatter, phosphatidylserine-exposure from annexin V binding, and [Ca2+]i from Fluo3-fluorescence. Results: Following a 48 hours incubation, the percentage of phosphatidylserine exposing erythrocytes markedly increased as a function of extracellular phosphate concentration (from 0-5 mM. The exposure to 2 mM or 5 mM phosphate was followed by slight but significant hemolysis. [Ca2+]i did not change significantly up to 2 mM phosphate but significantly decreased at 5 mM phosphate. The effect of 2 mM phosphate on phosphatidylserine exposure was significantly augmented by increase of extracellular Ca2+ to 1.7 mM, and significantly blunted by nominal absence of extracellular Ca2+, by additional presence of pyrophosphate as well as by presence of p38 inhibitor SB203580. Conclusion: Increasing phosphate concentration stimulates erythrocyte membrane scrambling, an effect depending on extracellular but not intracellular Ca2+ concentration. It is hypothesized that suicidal erythrocyte death is triggered by complexed CaHPO4.

  2. Short-term beat-to-beat variability of the QT interval is increased and correlates with parameters of left ventricular hypertrophy in patients with hypertrophic cardiomyopathy.

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    Orosz, Andrea; Baczkó, István; Nagy, Viktória; Gavallér, Henriette; Csanády, Miklós; Forster, Tamás; Papp, Julius Gy; Varró, András; Lengyel, Csaba; Sepp, Róbert

    2015-09-01

    Stratification models for the prediction of sudden cardiac death (SCD) are inappropriate in patients with hypertrophic cardiomyopathy (HCM). We investigated conventional electrocardiogram (ECG) repolarization parameters and the beat-to-beat short-term QT interval variability (QT-STV), a new parameter of proarrhythmic risk, in 37 patients with HCM (21 males, average age 48 ± 15 years). Resting ECGs were recorded for 5 min and the frequency corrected QT interval (QTc), QT dispersion (QTd), beat-to-beat short-term variability of QT interval (QT-STV), and the duration of terminal part of T waves (Tpeak-Tend) were calculated. While all repolarization parameters were significantly increased in patients with HCM compared with the controls (QTc, 488 ± 61 vs. 434 ± 23 ms, p < 0.0001; QT-STV, 4.5 ± 2 vs. 3.2 ± 1 ms, p = 0.0002; Tpeak-Tend duration, 107 ± 27 vs. 91 ± 10 ms, p = 0.0015; QTd, 47 ± 17 vs. 34 ± 9 ms, p = 0.0002), QT-STV had the highest relative increase (+41%). QT-STV also showed the best correlation with indices of left ventricular (LV) hypertrophy, i.e., maximal LV wall thickness normalized for body surface area (BSA; r = 0.461, p = 0.004) or LV mass (determined by cardiac magnetic resonance imaging) normalized for BSA (r = 0.455, p = 0.015). In summary, beat-to-beat QT-STV showed the most marked increase in patients with HCM and may represent a novel marker that merits further testing for increased SCD risk in HCM.

  3. Faster cross-bridge detachment and increased tension cost in human hypertrophic cardiomyopathy with the R403Q MYH7 mutation.

    Science.gov (United States)

    Witjas-Paalberends, E Rosalie; Ferrara, Claudia; Scellini, Beatrice; Piroddi, Nicoletta; Montag, Judith; Tesi, Chiara; Stienen, Ger J M; Michels, Michelle; Ho, Carolyn Y; Kraft, Theresia; Poggesi, Corrado; van der Velden, Jolanda

    2014-08-01

    The first mutation associated with hypertrophic cardiomyopathy (HCM) is the R403Q mutation in the gene encoding β-myosin heavy chain (β-MyHC). R403Q locates in the globular head of myosin (S1), responsible for interaction with actin, and thus motor function of myosin. Increased cross-bridge relaxation kinetics caused by the R403Q mutation might underlie increased energetic cost of tension generation; however, direct evidence is absent. Here we studied to what extent cross-bridge kinetics and energetics are related in single cardiac myofibrils and multicellular cardiac muscle strips of three HCM patients with the R403Q mutation and nine sarcomere mutation-negative HCM patients (HCMsmn). Expression of R403Q was on average 41 ± 4% of total MYH7 mRNA. Cross-bridge slow relaxation kinetics in single R403Q myofibrils was significantly higher (P < 0.0001) than in HCMsmn myofibrils (0.47 ± 0.02 and 0.30 ± 0.02 s(-1), respectively). Moreover, compared to HCMsmn, tension cost was significantly higher in the muscle strips of the three R403Q patients (2.93 ± 0.25 and 1.78 ± 0.10 μmol l(-1) s(-1) kN(-1) m(-2), respectively) which showed a positive linear correlation with relaxation kinetics in the corresponding myofibril preparations. This correlation suggests that faster cross-bridge relaxation kinetics results in an increase in energetic cost of tension generation in human HCM with the R403Q mutation compared to HCMsmn. Therefore, increased tension cost might contribute to HCM disease in patients carrying the R403Q mutation. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

  4. Omentin functions to attenuate cardiac hypertrophic response.

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    Matsuo, Kazuhiro; Shibata, Rei; Ohashi, Koji; Kambara, Takahiro; Uemura, Yusuke; Hiramatsu-Ito, Mizuho; Enomoto, Takashi; Yuasa, Daisuke; Joki, Yusuke; Ito, Masanori; Hayakawa, Satoko; Ogawa, Hayato; Kihara, Shinji; Murohara, Toyoaki; Ouchi, Noriyuki

    2015-02-01

    Cardiac hypertrophy occurs in many obesity-related conditions. Omentin is an adipose-derived plasma protein that is downregulated under obese conditions. Here, we investigated whether omentin modulates cardiac hypertrophic responses in vivo and in vitro. Systemic administration of an adenoviral vector expressing human omentin (Ad-OMT) to wild-type (WT) mice led to the attenuation of cardiac hypertrophy, fibrosis and ERK phosphorylation induced by transverse aortic constriction (TAC) or angiotensin II infusion. In cultured cardiomyocytes, stimulation with phenylephrine (PE) led to an increase in myocyte size, which was prevented by pretreatment with human omentin protein. Pretreatment of cardiomyocytes with omentin protein also reduced ERK phosphorylation in response to PE stimulation. Ad-OMT enhanced phosphorylation of AMP-activated protein kinase (AMPK) in the heart of WT mice after TAC operation. Blockade of AMPK activation by transduction with dominant-negative mutant forms of AMPK reversed the inhibitory effect of omentin on myocyte hypertrophy and ERK phosphorylation following PE stimulation. Moreover, fat-specific transgenic mice expressing human omentin showed reduced cardiac hypertrophy and ERK phosphorylation following TAC surgery compared to littermate controls. These data suggest that omentin functions to attenuate the pathological process of myocardial hypertrophy via the activation of AMPK in the heart, suggesting that omentin may represent a target molecule for the treatment of cardiac hypertrophy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Evaluation of left ventricular torsion in children with hypertrophic cardiomyopathy.

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    Prinz, Christian; Faber, Lothar; Horstkotte, Dieter; Körperich, Hermann; Moysich, Axel; Haas, Nikolaus; Kececioglu, Deniz; Thorsten Laser, Kai

    2014-04-01

    To evaluate the role of torsion in hypertrophic cardiomyopathy in children. A total of 88 children with idiopathic hypertrophic cardiomyopathy (n = 24) and concentric hypertrophy (n = 20) were investigated with speckle-tracking echocardiography and compared with age- and gender-matched healthy controls (n = 44). In hypertrophic cardiomyopathy, we found increased torsion (2.8 ± 1.6 versus 1.9 ± 1.0°/cm [controls], p Hypertrophic cardiomyopathy patients demonstrated a negative correlation between left ventricular muscle mass and torsion (r = -0.7, p hypertrophic cardiomyopathy is characterised by predominantly enhanced systolic basal clockwise rotation. Diastolic untwisting is delayed in both groups. Torsion may be an interesting marker to guide patients with hypertrophic cardiomyopathy.

  6. Increasing honesty in humans with noninvasive brain stimulation.

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    Maréchal, Michel André; Cohn, Alain; Ugazio, Giuseppe; Ruff, Christian C

    2017-04-25

    Honesty plays a key role in social and economic interactions and is crucial for societal functioning. However, breaches of honesty are pervasive and cause significant societal and economic problems that can affect entire nations. Despite its importance, remarkably little is known about the neurobiological mechanisms supporting honest behavior. We demonstrate that honesty can be increased in humans with transcranial direct current stimulation (tDCS) over the right dorsolateral prefrontal cortex. Participants (n = 145) completed a die-rolling task where they could misreport their outcomes to increase their earnings, thereby pitting honest behavior against personal financial gain. Cheating was substantial in a control condition but decreased dramatically when neural excitability was enhanced with tDCS. This increase in honesty could not be explained by changes in material self-interest or moral beliefs and was dissociated from participants' impulsivity, willingness to take risks, and mood. A follow-up experiment (n = 156) showed that tDCS only reduced cheating when dishonest behavior benefited the participants themselves rather than another person, suggesting that the stimulated neural process specifically resolves conflicts between honesty and material self-interest. Our results demonstrate that honesty can be strengthened by noninvasive interventions and concur with theories proposing that the human brain has evolved mechanisms dedicated to control complex social behaviors.

  7. Thyroid stimulating hormone increases hepatic gluconeogenesis via CRTC2.

    Science.gov (United States)

    Li, Yujie; Wang, Laicheng; Zhou, Lingyan; Song, Yongfeng; Ma, Shizhan; Yu, Chunxiao; Zhao, Jiajun; Xu, Chao; Gao, Ling

    2017-05-05

    Epidemiological evidence indicates that thyroid stimulating hormone (TSH) is positively correlated with abnormal glucose levels. We previously reported that TSH has direct effects on gluconeogenesis. However, the underlying molecular mechanism remains unclear. In this study, we observed increased fasting blood glucose and glucose production in a mouse model of subclinical hypothyroidism (only elevated TSH levels). TSH acts via the classical cAMP/PKA pathway and CRTC2 regulates glucose homeostasis. Thus, we explore whether CRTC2 is involved in the process of TSH-induced gluconeogenesis. We show that TSH increases CRTC2 expression via the TSHR/cAMP/PKA pathway, which in turn upregulates hepatic gluconeogenic genes. Furthermore, TSH stimulates CRTC2 dephosphorylation and upregulates p-CREB (Ser133) in HepG2 cells. Silencing CRTC2 and CREB decreases the effect of TSH on PEPCK-luciferase, the rate-limiting enzyme of gluconeogenesis. Finally, the deletion of TSHR reduces the levels of the CRTC2:CREB complex in mouse livers. This study demonstrates that TSH activates CRTC2 via the TSHR/cAMP/PKA pathway, leading to the formation of a CRTC2:CREB complex and increases hepatic gluconeogenesis. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Total substitution of dietary fish oil by vegetable oils stimulates muscle hypertrophic growth in Senegalese sole and the upregulation of fgf6.

    Science.gov (United States)

    Lopes, Graciliana; Castro, Luís Filipe Costa; Valente, Luísa Maria Pinheiro

    2017-05-24

    The long term effects of fish oil (FO) substitution by increasing the levels of vegetable oils (VO), 0% (CTR), 50% (VO50) and 100% (VO100), in diets for Senegalese sole were evaluated in terms of skeletal muscle cellularity and expression of related genes. After 140 days of feeding, all fish had similar body weight and length. The inclusion of 50% VO did not result in differences in muscle cellularity, but dorsal muscle cross-sectional area and fast-twitch fibre diameter increased in fish fed total FO substitution, whilst fibre density was reduced (P growth, but not hyperplastic growth, and associated with a nutritional modulation of fgf6 by dietary VO. This study indicates that 50% VO does not affect the muscle phenotype, but total FO substitution stimulates muscle hypertrophy.

  9. Hypertrophic phenotype in cardiac cell assemblies solely by structural cues and ensuing self-organization.

    Science.gov (United States)

    Chung, Chiung-yin; Bien, Harold; Sobie, Eric A; Dasari, Vikram; McKinnon, David; Rosati, Barbara; Entcheva, Emilia

    2011-03-01

    In vitro models of cardiac hypertrophy focus exclusively on applying "external" dynamic signals (electrical, mechanical, and chemical) to achieve a hypertrophic state. In contrast, here we set out to demonstrate the role of "self-organized" cellular architecture and activity in reprogramming cardiac cell/tissue function toward a hypertrophic phenotype. We report that in neonatal rat cardiomyocyte culture, subtle out-of-plane microtopographic cues alter cell attachment, increase biomechanical stresses, and induce not only structural remodeling, but also yield essential molecular and electrophysiological signatures of hypertrophy. Increased cell size and cell binucleation, molecular up-regulation of released atrial natriuretic peptide, altered expression of classic hypertrophy markers, ion channel remodeling, and corresponding changes in electrophysiological function indicate a state of hypertrophy on par with other in vitro and in vivo models. Clinically used antihypertrophic pharmacological treatments partially reversed hypertrophic behavior in this in vitro model. Partial least-squares regression analysis, combining gene expression and functional data, yielded clear separation of phenotypes (control: cells grown on flat surfaces; hypertrophic: cells grown on quasi-3-dimensional surfaces and treated). In summary, structural surface features can guide cardiac cell attachment, and the subsequent syncytial behavior can facilitate trophic signals, unexpectedly on par with externally applied mechanical, electrical, and chemical stimulation.

  10. HYPERTROPHIC OBSTRUCTIVE CARDIOMYOPATHY

    Directory of Open Access Journals (Sweden)

    A. G. Osiev

    2015-01-01

    Full Text Available Hypertrophic cardiomyopathy (HCMP is a relatively common disease with genetic predisposition, that is widely spread irrespective of gender, race or ethnicity. The cause of this pathology are mutations of genes encoding synthesis of contracting proteins. Degree and type of mutations define clinical manifestation of the disease and its prognosis. HCMP is classified according to four main criteria: depending on morphology, presence of left ventricular outlet obstruction, pressure gradient and hemodynamic parameters. Its prevalence amounts to 1:500, and in the recent years mortality has decreased significantly to 1%. Main symptoms of HCMP include dyspnoea, dizziness, syncope, angina, and heart arrhythmias. HCMP does not manifest obligatorily with all above mentioned signs and symptoms. Presence and severity of any symptoms depend on morphological particulars of the disease. Particular attention should be paid to arrhythmias, with atrial fibrillation among them, that may cause hazardous and occasionally lethal complications. Electrocardiography and echocardiography are recognized as the “golden standard” of HCMP diagnostics, while in the recent years, magnetic resonance imaging has become a highly informative diagnostic tool. Radionuclide diagnostics is used less frequently, while physical examination and assessments have been moving backwards. At present, main strategies in HCMP include medical treatment with β-blockers, calcium antagonists, angiotensin-converting enzyme inhibitors and anti-arrhythmics. There are two techniques for surgical treatment, i.e. myectomy by Morrow and alcohol septal ablation that is becoming increasingly popular. The article reviews literature on state-of-the-art diagnostics and treatment of HCMP patients.

  11. HYPERTROPHIC CARDIOMYOPATHY IN MULTIMORBIDITY

    Directory of Open Access Journals (Sweden)

    A. I. Lakhonina

    2016-06-01

    Full Text Available Aspects of diagnosis, difficulties in the diagnosis and optimal therapeutic strategies in patient with hypertrophic cardiomyopathy and comorbid conditions such as arterial hypertension, ischemic heart disease, dyslipidemia, diabetes mellitus type 2, stenosis of the left renal artery, obesity are reviewed on the example of clinical case. Hypertrophic cardiomyopathy combined with multimorbidity conditions requires a high-quality medical management, where the main goal is to improve the quality and duration of patient's life. This goal is being achieved by optimizing patient's lifestyle and assigning only the minimum amount of medications. Necessity of careful diagnosis of hypertrophic cardiomyopathy, evaluation of the risk of sudden death and search of optimal treatment in patients with multimorbidity pathology are demonstrated in clinical case.

  12. Hypertrophic pachymeningitis: case report

    Directory of Open Access Journals (Sweden)

    Deus-Silva Leonardo de

    2003-01-01

    Full Text Available Hypertrophic pachymeningits is an unusual cause of neurological symptoms and is often secondary to infections, carcinomatosis or inflammatory diseases. It may also be idiopathic. We report a case of pachymeningitis which was manifested primarily by psychosis and visual loss with optic atrophy and destruction of nasal septum. The patient, a 45 year old woman was submitted to extensive investigation without evidence of any underlying disease. A meningeal biopsy was performed and showed a mostly unspecific inflammatory process with extensive fibrosis of the dura and few early stage granulomas. These findings suggest either neurosarcoidosis or idiopathic hypertrophic pachymeningitis.

  13. Psychosocial impact of specialized cardiac genetic clinics for hypertrophic cardiomyopathy.

    Science.gov (United States)

    Ingles, Jodie; Lind, Joanne M; Phongsavan, Philayrath; Semsarian, Christopher

    2008-02-01

    The diagnosis of hypertrophic cardiomyopathy, an autosomal dominant chronic heart disease, can have significant implications, including increased risk of sudden death, exercise limitations, and risk of transmission to offspring. This study sought to describe the psychosocial factors associated with attending a specialty cardiac genetic clinic, and to determine whether these may be predictors of comorbid anxiety and depression in this population. Questionnaires were sent to 184 individuals attending the Royal Prince Alfred Hospital Hypertrophic Cardiomyopathy Clinic. Questionnaires were anonymous and comprised demographics, the Hospital Anxiety and Depression Scale, Patient Experience Scales, and Patient Satisfaction Scales. Completed questionnaires were returned by 109 participants (59.2% response rate), of which 76.9% had a diagnosis of hypertrophic cardiomyopathy, while 23.1% were at-risk relatives attending for clinical screening. Patient satisfaction scores were generally high to very high across all groups, though only 24% of HCM patients showed good adjustment to hypertrophic cardiomyopathy and 10% had low worry about hypertrophic cardiomyopathy scores. Within the disease group, logistic regression analysis adjusting for age, gender, and education revealed adjustment to hypertrophic cardiomyopathy and worry about hypertrophic cardiomyopathy scores to be significantly associated with anxiety, while adjustment scores and location of patient follow-up (i.e., Hypertrophic Cardiomyopathy clinic or another cardiologist) to be significantly associated with depression scores. HCM patients who attend specialized cardiac genetic clinics are better adjusted and worry less, than those who do not attend. An integrated approach, including a genetic counselor, is important in the management of HCM families.

  14. Infantile hypertrophic pyloric stenosis

    DEFF Research Database (Denmark)

    Pedersen, Rikke Neess; Garne, Ester; Loane, Maria

    2008-01-01

    OBJECTIVE: The objective of this study was to present epidemiologic data on infantile hypertrophic pyloric stenosis (IHPS) from seven well-defined European regions, and to compare incidence and changes in incidence over time between these regions. METHODS: This was a population-based study using...

  15. Sacral nerve stimulation increases activation of the primary somatosensory cortex by anal canal stimulation in an experimental model.

    LENUS (Irish Health Repository)

    Griffin, K M

    2011-08-01

    Sacral and posterior tibial nerve stimulation may be used to treat faecal incontinence; however, the mechanism of action is unknown. The aim of this study was to establish whether sensory activation of the cerebral cortex by anal canal stimulation was increased by peripheral neuromodulation.

  16. Follicle-Stimulating Hormone Increases the Risk of Postmenopausal Osteoporosis by Stimulating Osteoclast Differentiation.

    Directory of Open Access Journals (Sweden)

    Jie Wang

    Full Text Available The objectives of this study were to observe the changes in follicle-stimulating hormone (FSH and bone mineral density (BMD in postmenopausal women, to research the relationship between FSH and postmenopausal osteoporosis, and to observe the effects of FSH on osteoclast differentiation in RAW264.7 cells.We analyzed 248 postmenopausal women with normal bone metabolism. A radioimmunoassay (RIA was used to detect serum FSH, luteinizing hormone (LH, and estradiol (E2. Dual-energy X-ray absorptiometry was used to measure forearm BMD. Then, we analyzed the age-related changes in serum FSH, LH and E2. Additionally, FSH serum concentrations were compared between a group of postmenopausal women with osteoporosis and a control group. Osteoclasts were induced from RAW264.7 cells in vitro by receptor activator of nuclear factor kappa B ligand (RANKL, and these cells were treated with 0, 5, 10, and 20 ng/ml FSH. After the osteoclasts matured, tartrate-resistant acid phosphatase (TRAP staining was used to identify osteoclasts, and the mRNA expression levels of genes involved in osteoclastic phenotypes and function, such as receptor activator of NF-κB (Rank, Trap, matrix metalloproteinase-9 (Mmp-9 and Cathepsin K, were detected in different groups using real-time PCR (polymerase chain reaction.1. FSH serum concentrations in postmenopausal women with osteoporosis increased notably compared with the control group. 2. RANKL induced RAW264.7 cell differentiation into mature osteoclasts in vitro. 3. FSH increased mRNA expression of genes involved in osteoclastic phenotypes and function, such as Rank, Trap, Mmp-9 and Cathepsin K, in a dose-dependent manner.The circulating concentration of FSH may play an important role in the acceleration of bone loss in postmenopausal women. FSH increases osteoclastogenesis in vitro.

  17. Follicle-Stimulating Hormone Increases the Risk of Postmenopausal Osteoporosis by Stimulating Osteoclast Differentiation.

    Science.gov (United States)

    Wang, Jie; Zhang, Wenwen; Yu, Chunxiao; Zhang, Xu; Zhang, Haiqing; Guan, Qingbo; Zhao, Jiajun; Xu, Jin

    2015-01-01

    The objectives of this study were to observe the changes in follicle-stimulating hormone (FSH) and bone mineral density (BMD) in postmenopausal women, to research the relationship between FSH and postmenopausal osteoporosis, and to observe the effects of FSH on osteoclast differentiation in RAW264.7 cells. We analyzed 248 postmenopausal women with normal bone metabolism. A radioimmunoassay (RIA) was used to detect serum FSH, luteinizing hormone (LH), and estradiol (E2). Dual-energy X-ray absorptiometry was used to measure forearm BMD. Then, we analyzed the age-related changes in serum FSH, LH and E2. Additionally, FSH serum concentrations were compared between a group of postmenopausal women with osteoporosis and a control group. Osteoclasts were induced from RAW264.7 cells in vitro by receptor activator of nuclear factor kappa B ligand (RANKL), and these cells were treated with 0, 5, 10, and 20 ng/ml FSH. After the osteoclasts matured, tartrate-resistant acid phosphatase (TRAP) staining was used to identify osteoclasts, and the mRNA expression levels of genes involved in osteoclastic phenotypes and function, such as receptor activator of NF-κB (Rank), Trap, matrix metalloproteinase-9 (Mmp-9) and Cathepsin K, were detected in different groups using real-time PCR (polymerase chain reaction). 1. FSH serum concentrations in postmenopausal women with osteoporosis increased notably compared with the control group. 2. RANKL induced RAW264.7 cell differentiation into mature osteoclasts in vitro. 3. FSH increased mRNA expression of genes involved in osteoclastic phenotypes and function, such as Rank, Trap, Mmp-9 and Cathepsin K, in a dose-dependent manner. The circulating concentration of FSH may play an important role in the acceleration of bone loss in postmenopausal women. FSH increases osteoclastogenesis in vitro.

  18. Pregnancy in women with hypertrophic cardiomyopathy

    NARCIS (Netherlands)

    Pieper, P. G.; Walker, F.

    Hypertrophic cardiomyopathy (HCM) is increasingly being diagnosed in pregnant women. Women with HCM generally tolerate pregnancy well. The risk is however higher in women who are symptomatic before pregnancy or in those with severe left ventricular outflow tract obstruction. The incidence of

  19. Genetics Home Reference: familial hypertrophic cardiomyopathy

    Science.gov (United States)

    ... Home Health Conditions Familial hypertrophic cardiomyopathy Familial hypertrophic cardiomyopathy Printable PDF Open All Close All Enable Javascript ... view the expand/collapse boxes. Description Familial hypertrophic cardiomyopathy is a heart condition characterized by thickening (hypertrophy) ...

  20. Clinical predictors of genetic testing outcomes in hypertrophic cardiomyopathy.

    Science.gov (United States)

    Ingles, Jodie; Sarina, Tanya; Yeates, Laura; Hunt, Lauren; Macciocca, Ivan; McCormack, Louise; Winship, Ingrid; McGaughran, Julie; Atherton, John; Semsarian, Christopher

    2013-12-01

    Genetic testing for hypertrophic cardiomyopathy has been commercially available for almost a decade; however, low mutation detection rate and cost have hindered uptake. This study sought to identify clinical variables that can predict probands with hypertrophic cardiomyopathy in whom a pathogenic mutation will be identified. Probands attending specialized cardiac genetic clinics across Australia over a 10-year period (2002-2011), who met clinical diagnostic criteria for hypertrophic cardiomyopathy and who underwent genetic testing for hypertrophic cardiomyopathy were included. Clinical, family history, and genotype information were collected. A total of 265 unrelated individuals with hypertrophic cardiomyopathy were included, with 138 (52%) having at least one mutation identified. The mutation detection rate was significantly higher in the probands with hypertrophic cardiomyopathy with an established family history of disease (72 vs. 29%, P < 0.0001), and a positive family history of sudden cardiac death further increased the detection rate (89 vs. 59%, P < 0.0001). Multivariate analysis identified female gender, increased left-ventricular wall thickness, family history of hypertrophic cardiomyopathy, and family history of sudden cardiac death as being associated with greatest chance of identifying a gene mutation. Multiple mutation carriers (n = 16, 6%) were more likely to have suffered an out-of-hospital cardiac arrest or sudden cardiac death (31 vs. 7%, P = 0.012). Family history is a key clinical predictor of a positive genetic diagnosis and has direct clinical relevance, particularly in the pretest genetic counseling setting.

  1. Process of Hypertrophic Scar Formation: Expression of Eukaryotic Initiation Factor 6

    Science.gov (United States)

    Yang, Qing-Qing; Yang, Si-Si; Tan, Jiang-Lin; Luo, Gao-Xing; He, Wei-Feng; Wu, Jun

    2015-01-01

    Background: Hypertrophic scar is one of the most common complications and often causes the disfigurement or deformity in burn or trauma patients. Therapeutic methods on hypertrophic scar treatment have limitations due to the poor understanding of mechanisms of hypertrophic scar formation. To throw light on the molecular mechanism of hypertrophic scar formation will definitely improve the outcome of the treatment. This study aimed to illustrate the negative role of eukaryotic initiation factor 6 (eIF6) in the process of human hypertrophic scar formation, and provide a possible indicator of hypertrophic scar treatment and a potential target molecule for hypertrophic scar. Methods: In the present study, we investigated the protein expression of eIF6 in the human hypertrophic scar of different periods by immunohistochemistry and Western blot analysis. Results: In the hypertrophic scar tissue, eIF6 expression was significantly decreased and absent in the basal layer of epidermis in the early period, and increased slowly and began to appear in the basal layer of epidermis by the scar formation time. Conclusions: This study confirmed that eIF6 expression was significantly related to the development of hypertrophic scar, and the eIF6 may be a target molecule for hypertrophic scar control or could be an indicator of the outcomes for other treatment modalities. PMID:26481747

  2. Contractile Dysfunction in Sarcomeric Hypertrophic Cardiomyopathy.

    Science.gov (United States)

    MacIver, David H; Clark, Andrew L

    2016-09-01

    The pathophysiological mechanisms underlying the clinical phenotype of sarcomeric hypertrophic cardiomyopathy are controversial. The development of cardiac hypertrophy in hypertension and aortic stenosis is usually described as a compensatory mechanism that normalizes wall stress. We suggest that an important abnormality in hypertrophic cardiomyopathy is reduced contractile stress (the force per unit area) generated by myocardial tissue secondary to abnormalities such as cardiomyocyte disarray. In turn, a progressive deterioration in contractile stress provokes worsening hypertrophy and disarray. A maintained or even exaggerated ejection fraction is explained by the increased end-diastolic wall thickness producing augmented thickening. We propose that the nature of the hemodynamic load in an individual with hypertrophic cardiomyopathy could determine its phenotype. Hypertensive patients with hypertrophic cardiomyopathy are more likely to develop exaggerated concentric hypertrophy; athletic individuals an asymmetric pattern; and inactive individuals a more apical hypertrophy. The development of a left ventricular outflow tract gradient and mitral regurgitation may be explained by differential regional strain resulting in mitral annular rotation. Copyright © 2016. Published by Elsevier Inc.

  3. Increasing bladder capacity by foot stimulation in rats with spinal cord injuries.

    Science.gov (United States)

    Chen, Guoqing; Liao, Limin; Wang, Zhaoxia; Li, Xing; Du, Wenjuan

    2017-09-15

    This study was to explore the possibility that foot stimulation increased bladder capacity(BC) in rats with neurogenic bladder secondary to T10 spinal cord injuries. In 20 awake rats (stimulation group) with T10 spinal cord injuries, 5 repeat cystometrograms (CMGs) were recorded. The 1st and 2nd CMGs were performed without stimulation. The 3rd, 4th, and 5th CMGs were done separately with 1 T, 2 T, and 4 T stimulation, respectively, through a pair of pad electrodes on the skin of the hind foot. In the control group of 20 rats, 5 repeat CMGs were recorded without foot stimulation. The threshold (T) was the minimal stimulation intensity to induce an observable toe twitch. In the stimulation group, foot stimulation with 2 T significantly increased the BC an additional 68.9% ± 20.82% (p stimulation with 4 T increased the BC an additional 120.9% ± 24.82% (p stimulation group, but the 4th (2 T) and 5th (4 T) CMGs were significantly increased (p stimulation of the foot was effective in inhibiting reflex bladder activity and increasing bladder capacity in spinal cord injury rats.

  4. Stimulation of shank muscles during functional electrical stimulation cycling increases ankle excursion in individuals with spinal cord injury.

    Science.gov (United States)

    Fornusek, Ché; Davis, Glen M; Baek, Ilhun

    2012-11-01

    To investigate the effect of shank muscle stimulation on ankle joint excursion during passive and functional electrical stimulation (FES) leg cycling. Within-subject comparisons. Laboratory setting. Well-trained FES cyclists (N=7) with chronic spinal cord injuries. Two experimental sessions were performed on an isokinetic FES cycle ergometer with a pedal boot that allowed the ankle to plantarflex and dorsiflex during cycling. During the first session, the optimal stimulation timings to induce plantarflexion and dorsiflexion were investigated by systematically altering the stimulation angles of the shank muscles (tibialis anterior [TA] and triceps surae [TS]). During the second session, TA and TS stimulation was included with standard FES cycling (quadriceps, hamstrings, and gluteals) for 6 subjects. Ankle, knee, and hip movements were analyzed using 2-dimensional video. The ankle excursions during passive cycling were 19°±6°. TA and TS stimulation increased ankle joint excursion up to 33°±10° and 27°±7°, respectively. Compared with passive cycling, ankle joint excursion was not significantly increased during standard FES cycling (24°±7°). TA and TS stimulation significantly increased the ankle excursion when applied during standard FES cycling (41°±4°). Freeing the ankle joint to rotate during FES cycling was found to be safe. The combination of shank muscle stimulation and repetitive ankle joint movement may be beneficial for improving ankle flexibility and leg conditioning. Further research is required to test and design ankle supports that might maximize the benefits of shank muscle activation. Copyright © 2012 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  5. Skin collagen reproduction increased by ascorbic acid derivative iontophoresis by frequent-reversal bipolar electric stimulation.

    Science.gov (United States)

    Hori, Yusuke; Akimoto, Ryuji; Hori, Akiko; Kato, Katsuhiko; Chino, Daisuke; Matsumoto, Shohei; Kamiya, Shohei; Watanabe, Yasuo

    2009-01-01

    The effect of the iontophoresis of ascorbic acid (Vitamin C; VC) derivative with frequent-reversal bipolar electric stimulation on the production of collagen in rat skin was evaluated in terms of hydroxyproline content through high-performance liquid chromatography. First, a control group was not given electrical stimulation and four groups were stimulated with a unipolar pulse for 0.5-10 min every day for one week. The hydroxyproline level in the skin was increased depending on the length of the stimulation. Second, a control group was not given any electrical stimulation, and three groups were treated with (a) VC solution without any stimulation, (b) a bipolar pulse for 10 min with saline, or (c) a bipolar pulse for 5 min with the VC solution. Significant increases were found in all the stimulation groups, although these treated with the VC solution without any stimulation did not have any effects compared to the control. Thus, in order to increase the hydroxyproline levels in skin, a VC must be delivered with bipolar stimulation as a method of iontophoresis. These results suggest that our newly developed electric stimulation is effective at increasing skin collagen content, and that bipolar stimulation is more effective on the iontophoresis of not only VC but also some medicines such as low- and high-molecular drugs directed to the target organ (7).

  6. Hypertrophic Cardiomyopathy: A Review

    Science.gov (United States)

    Houston, Brian A; Stevens, Gerin R

    2014-01-01

    Hypertrophic cardiomyopathy (HCM) is a global disease with cases reported in all continents, affecting people of both genders and of various racial and ethnic origins. Widely accepted as a monogenic disease caused by a mutation in 1 of 13 or more sarcomeric genes, HCM can present catastrophically with sudden cardiac death (SCD) or ventricular arrhythmias or insidiously with symptoms of heart failure. Given the velocity of progress in both the fields of heart failure and HCM, we present a review of the approach to patients with HCM, with particular attention to those with HCM and the clinical syndrome of heart failure. PMID:25657602

  7. Elevated Level of Troponin but Not N-Terminal Probrain Natriuretic Peptide Is Associated with Increased Risk of Sudden Cardiac Death in Hypertrophic Cardiomyopathy Calculated According to the ESC Guidelines 2014

    Directory of Open Access Journals (Sweden)

    Renata Rajtar-Salwa

    2017-01-01

    Full Text Available The aim of this study was to assess the relationship between biomarkers (high-sensitive troponin I [hs-TnI], N-Terminal probrain natriuretic peptide [NT-proBNP] and calculated 5-year percentage risk score of sudden cardiac death (SCD in hypertrophic cardiomyopathy (HCM. Methods. In 46 HCM patients (mean age 39 ± 7 years, 24 males and 22 females, echocardiographic examination, including the stimulating maneuvers to provoke maximized LVOT gradient, had been performed and next ECG Holter was immediately started. After 24 hours, the ECG Holter was finished and the hs-TnI and NT-proBNP have been measured. Patients were divided according to 1/value of both biomarkers (hs-TnI-positive and hs-TnI-negative subgroups and 2/(NT-proBNP lower and higher subgroup divided by median. Results. In comparison between 19 patients (hs-TnI positive versus 27 patients (hs-TnI negative, the calculated 5-year percentage risk of SCD in HCM was significantly greater (6.38 ± 4.17% versus 3.81 ± 3.23%, P0.05. Conclusions. Patients with HCM and positive hs-TnI test have a higher risk of SCD estimated according to SCD calculator recommended by the ESC Guidelines 2014 than patients with negative hs-TnI test.

  8. Investigating the role of P311 in the hypertrophic scar.

    Directory of Open Access Journals (Sweden)

    Jianglin Tan

    Full Text Available The mechanisms of hypertrophic scar formation are not fully understood. We previously screened the differentially expressed genes of human hypertrophic scar tissue and identified P311 gene as upregulated. As the activities of P311 in human fibroblast function are unknown, we examined the distribution of it and the effects of forced expression or silencing of expression of P311. P311 expression was detected in fibroblast-like cells from the hypertrophic scar of burn injury patients but not in peripheral blood mononuclear cells, bone marrow mesenchymal stem cells, epidermal cells or normal skin dermal cells. Transfection of fibroblasts with P311 gene stimulated the expression of alpha-smooth muscle actin (alpha-SMA, TGF-beta1 and alpha1(I collagen (COL1A1, and enhanced the contraction of fibroblast populated collagen lattices (FPCL. In contrast, interference of fibroblast P311 gene expression decreased the TGF-beta1 mRNA expression and reduced the contraction of fibroblasts in FPCL. These results suggest that P311 may be involved in the pathogenesis of hypertrophic scar via induction of a myofibroblastic phenotype and of functions such as TGF-beta1 expression. P311 could be a novel target for the control of hypertrophic scar development.

  9. Primary hypertrophic osteoarthropathy: ultrasound and MRI findings

    Energy Technology Data Exchange (ETDEWEB)

    Adams, Brook; Kraft, Jeannette K. [Leeds Children' s Hospital at The Leeds General Infirmary, Clarendon Wing Radiology Department, Leeds, West Yorkshire (United Kingdom); Amin, Tania; Leone, Valentina; Wood, Mark [Leeds Children' s Hospital at The Leeds General Infirmary, Department of Paediatric Rheumatology, Leeds (United Kingdom)

    2016-05-15

    Primary hypertrophic osteoarthropathy is a rare genetic disorder related to failures in prostaglandin metabolism. Patients present with joint pain, limb enlargement, skin thickening and finger clubbing. Radiographs show characteristic periosteal reaction and thickening along the long bones. We present MRI and US findings in a child with the condition. Ultrasound showed echogenic tissue surrounding the long bones, presumably reflecting oedema and inflammatory tissue. Doppler sonograms demonstrated increased vascularity on the surface of some superficial bony structures. (orig.)

  10. Misconceptions and Facts About Hypertrophic Cardiomyopathy.

    Science.gov (United States)

    Argulian, Edgar; Sherrid, Mark V; Messerli, Franz H

    2016-02-01

    Hypertrophic cardiomyopathy is the most common genetic heart disease. Once considered relentless, untreatable, and deadly, it has become a highly treatable disease with contemporary management. Hypertrophic cardiomyopathy is one of cardiology's "great masqueraders." Mistakes and delays in diagnosis abound. Hypertrophic cardiomyopathy commonly "masquerades" as asthma, anxiety, mitral prolapse, and coronary artery disease. However, once properly diagnosed, patients with hypertrophic cardiomyopathy can be effectively managed to improve both symptoms and survival. This review highlights some of the misconceptions about hypertrophic cardiomyopathy. Providers at all levels should have awareness of hypertrophic cardiomyopathy to promptly diagnose and properly manage these individuals. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. The embryological basis of subclinical hypertrophic cardiomyopathy.

    Science.gov (United States)

    Captur, Gabriella; Ho, Carolyn Y; Schlossarek, Saskia; Kerwin, Janet; Mirabel, Mariana; Wilson, Robert; Rosmini, Stefania; Obianyo, Chinwe; Reant, Patricia; Bassett, Paul; Cook, Andrew C; Lindsay, Susan; McKenna, William J; Mills, Kevin; Elliott, Perry M; Mohun, Timothy J; Carrier, Lucie; Moon, James C

    2016-06-21

    Hypertrophic cardiomyopathy (HCM) is caused by mutations in sarcomeric proteins, the commonest being MYBPC3 encoding myosin-binding protein C. It is characterised by left ventricular hypertrophy but there is an important pre-hypertrophic phenotype with features including crypts, abnormal mitral leaflets and trabeculae. We investigated these during mouse cardiac development using high-resolution episcopic microscopy. In embryonic hearts from wildtype, homozygous (HO) and heterozygous (HET) Mybpc3-targeted knock-out (KO) mice we show that crypts (one or two) are a normal part of wildtype development but they almost all resolve by birth. By contrast, HO and HET embryos had increased crypt presence, abnormal mitral valve formation and alterations in the compaction process. In scarce normal human embryos, crypts were sometimes present. This study shows that features of the human pre-hypertrophic HCM phenotype occur in the mouse. In an animal model we demonstrate that there is an embryological HCM phenotype. Crypts are a normal part of cardiac development but, along with the mitral valve and trabeculae, their developmental trajectory is altered by the presence of HCM truncating Mybpc3 gene mutation.

  12. Epinephrine-stimulated glycogen breakdown activates glycogen synthase and increases insulin-stimulated glucose uptake in epitrochlearis muscles

    DEFF Research Database (Denmark)

    Kolnes, Anders J; Birk, Jesper Bratz; Eilertsen, Einar

    2015-01-01

    Adrenaline increases glycogen synthase (GS) phosphorylation and decreases GS activity but also stimulates glycogen breakdown and low glycogen content normally activates GS. To test the hypothesis that glycogen content directly regulates GS phosphorylation, glycogen breakdown was stimulated...... in condition with decreased GS activation. Saline or adrenaline (0.02mg/100g rat) was injected subcutaneously in Wistar rats (~130 g) with low (24 h fasted), normal (normal diet) and high glycogen content (fasted-refed) and epitrochlearis muscles were removed after 3 h and incubated ex vivo eliminating...... adrenaline action. Adrenaline injection reduced glycogen content in epitrochlearis muscles with high (120.7±17.8 vs 204.6±14.5 mmol•kg(-1); pglycogen (89.5±7.6 vs 152.6±8.1 mmol•kg(-1); pglycogen (90.0±5.0 vs 102.8±7.8 mmol•kg(-1); p=0...

  13. Pulsed Light Stimulation Increases Boundary Preference and Periodicity of Episodic Motor Activity in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Shuang Qiu

    Full Text Available There is considerable interest in the therapeutic benefits of long-term sensory stimulation for improving cognitive abilities and motor performance of stroke patients. The rationale is that such stimulation would activate mechanisms of neural plasticity to promote enhanced coordination and associated circuit functions. Experimental approaches to characterize such mechanisms are needed. Drosophila melanogaster is one of the most attractive model organisms to investigate neural mechanisms responsible for stimulation-induced behaviors with its powerful accessibility to genetic analysis. In this study, the effect of chronic sensory stimulation (pulsed light stimulation on motor activity in w1118 flies was investigated. Flies were exposed to a chronic pulsed light stimulation protocol prior to testing their performance in a standard locomotion assay. Flies responded to pulsed light stimulation with increased boundary preference and travel distance in a circular arena. In addition, pulsed light stimulation increased the power of extracellular electrical activity, leading to the enhancement of periodic electrical activity which was associated with a centrally-generated motor pattern (struggling behavior. In contrast, such periodic events were largely missing in w1118 flies without pulsed light treatment. These data suggest that the sensory stimulation induced a response in motor activity associated with the modifications of electrical activity in the central nervous system (CNS. Finally, without pulsed light treatment, the wild-type genetic background was associated with the occurrence of the periodic activity in wild-type Canton S (CS flies, and w+ modulated the consistency of periodicity. We conclude that pulsed light stimulation modifies behavioral and electrophysiological activities in w1118 flies. These data provide a foundation for future research on the genetic mechanisms of neural plasticity underlying such behavioral modification.

  14. Overexpression of mitofilin in the mouse heart promotes cardiac hypertrophy in response to hypertrophic stimuli.

    Science.gov (United States)

    Zhang, Yuan; Xu, Jing; Luo, Yu-Xuan; An, Xi-Zhou; Zhang, Ran; Liu, Guang; Li, Hongliang; Chen, Hou-Zao; Liu, De-Pei

    2014-10-20

    Mitofilin was originally described as a heart muscle protein because of its abundance in the heart tissue; however, its function in the heart is still to be elucidated. Thus, this study aims at investigating the role of mitofilin in the heart in response to hypertrophic stimuli. In this study, a significant increase in mitofilin expression was observed in the hearts of patients with hypertrophic cardiomyopathy. Transgenic (TG) mice with cardiomyocyte-specific overexpression of mitofilin were generated, and cardiac hypertrophy was introduced by transverse aortic constriction (TAC) or chronic infusion of isoproterenol (ISO). In TG mice overexpressing mitofilin, the level of cardiac hypertrophy was significantly greater than that in wild-type (WT) mice after TAC and ISO stimulation. A detailed analysis showed that compared with WT mice, the level of reactive oxygen species was increased after TAC and ISO induction and mitochondrial oxidative phosphorylation (OXPHOS) activity in the TG hearts was lower. These alterations may contribute to the aggravated cardiac hypertrophy observed in response to TAC and ISO stimulation. Over-expression of mitofilin promotes cardiac hypertrophy under pathological conditions both in vivo and in vitro. Mitofilin, a mitochondria protein, is shown to be related to cardiac hypertrophy for the first time, which enhances our understanding of the role of mitochondria in cardiac hypertrophy.

  15. Increased follicle-stimulating hormone is associated with higher assisted reproduction use after vasectomy reversal.

    Science.gov (United States)

    Hsiao, Wayland; Sultan, Raymond; Lee, Richard; Goldstein, Marc

    2011-06-01

    Of men with vasectomy 6% elect to have more children. When considering vasectomy reversal vs in vitro fertilization/intracytoplasmic sperm injection, an elucidation of preoperative factors that predict surgical success would help determine appropriate management. We tested the hypothesis that preoperative follicle-stimulating hormone 10 U/l or greater predict a lower paternity rate after vasectomy reversal. Using preoperative follicle-stimulating hormone levels we retrospectively reviewed the records of patients who underwent vasectomy reversal. Follicle-stimulating hormone was measured in cases suspicious for impaired spermatogenesis. The final analysis included 206 men, who were divided by follicle-stimulating hormone less than 10 U/l (normal in 155) and 10 U/l or greater (high in 51). Nominal logistic regression was performed to evaluate assisted reproduction predictors. Mean ± SD follicle-stimulating hormone in the normal and high groups was 5.1 ± 2.2 and 16.2 ± 6.2 U/l, respectively. Postoperative semen parameters were similar. However, in the high hormone group there was greater use of any type of assisted reproduction (78.4% vs 54.8%, p = 0.0028). On multivariate analysis follicle-stimulating hormone 10 U/l or greater (OR 3.02, 95% CI 1.34-6.83) and vasoepididymostomy that was bilateral or to a solitary testis (OR 3.26, 95% CI 1.09-9.69) was associated with greater assisted reproduction use. We evaluated preoperative follicle-stimulating hormone as a predictor of reproductive outcome in men with suspected subfertility who underwent vasectomy reversal. Increased follicle-stimulating hormone was associated with a higher rate of assisted reproduction even after controlling for confounding covariates. Thus, men with increased follicle-stimulating hormone should be counseled on the increased likelihood of needing assisted reproduction to achieve pregnancy after vasectomy reversal. Copyright © 2011 American Urological Association Education and Research, Inc

  16. Do prescription stimulants increase the risk of adverse cardiovascular events?: A systematic review

    Directory of Open Access Journals (Sweden)

    Westover Arthur N

    2012-06-01

    Full Text Available Abstract Background There is increasing concern that prescription stimulants may be associated with adverse cardiovascular events such as stroke, myocardial infarction, and sudden death. Public health concerns are amplified by increasing use of prescription stimulants among adults. Methods The objective of this study was to conduct a systematic review of the evidence of an association between prescription stimulant use and adverse cardiovascular outcomes. PUBMED, MEDLINE, EMBASE and Google Scholar searches were conducted using key words related to these topics (MESH: ADHD; Adults; Amphetamine; Amphetamines; Arrhythmias, Cardiac; Cardiovascular Diseases; Cardiovascular System; Central Nervous Stimulants; Cerebrovascular; Cohort Studies; Case–control Studies; Death; Death, Sudden, Cardiac; Dextroamphetamine; Drug Toxicity; Methamphetamine; Methylphenidate; Myocardial Infarction; Stimulant; Stroke; Safety. Eligible studies were population-based studies of children, adolescents, or adults using prescription stimulant use as the independent variable and a hard cardiovascular outcome as the dependent variable. Results Ten population-based observational studies which evaluated prescription stimulant use with cardiovascular outcomes were reviewed. Six out of seven studies in children and adolescents did not show an association between stimulant use and adverse cardiovascular outcomes. In contrast, two out of three studies in adults found an association. Conclusions Findings of an association between prescription stimulant use and adverse cardiovascular outcomes are mixed. Studies of children and adolescents suggest that statistical power is limited in available study populations, and the absolute risk of an event is low. More suggestive of a safety signal, studies of adults found an increased risk for transient ischemic attack and sudden death/ventricular arrhythmia. Interpretation was limited due to differences in population, cardiovascular outcome

  17. DIFFERENTIAL DIAGNOSIS OF HYPERTROPHIC CARDIOMYOPATHY

    Directory of Open Access Journals (Sweden)

    I. V. Leontyeva

    2017-01-01

    Full Text Available Hypertrophic cardiomyopathy is the most common form of cardiomyopathy, occurring in childhood, occurring when a gene is mutated that encodes proteins of sarcomeric and non-sarcomeric complexes. The diagnosis of the disease is based on the data of echocardiography, revealing structural changes in the heart muscle according to the type of hypertrophy, while the genesis of these changes remains unclear. The causes of hypertrophic cardiomyopathy in childhood are diverse. Of great importance is the early diagnosis of metabolic forms of hypertrophic cardiomyopathy, so in some cases regress of hypertrophy is possible against the background of enzyme-substitution or other drug therapy. The article presents a clinical (cardiac and extracardiac symptoms and laboratory markers of hypertrophic cardiomyopathy with mutations of genes of proteins of the sarcomeric complex, congenital metabolic disorders (glycogenoses, lysosomal pathology, fatty acid metabolism disorders, and mitochondrial diseases, genetic syndromes (Noonan, LEOPARD, Costello, cardio-fascial-cutaneous, neuromuscular diseases. The criteria for differential diagnosis of genetic forms of hypertrophic cardiomyopathy and myocardial hypertrophy in athletes are presented. 

  18. Infrared (IR) stimulated luminescence from feldspars with linearly increasing excitation light intensity

    CERN Document Server

    Bulur, E

    1999-01-01

    IR stimulated luminescence signal from potassium and sodium feldspars were studied by linearly increasing the excitation power from zero to a maximum value during the readout. The peak shaped signals observed in both feldspars could be approximated using a linear combination of three first-order components as deduced by curve fitting. The thermal and radiation dose dependent behavior of the IR-stimulated OSL curves were also studied.

  19. Increasing infection rate in multiple implanted pulse generator changes in movement disorder patients treated with deep brain stimulation

    DEFF Research Database (Denmark)

    Thrane, Jens F; Sunde, Niels A; Bergholt, Bo

    2014-01-01

    Increasing infection rate in multiple implanted pulse generator changes in movement disorder patients treated with deep brain stimulation......Increasing infection rate in multiple implanted pulse generator changes in movement disorder patients treated with deep brain stimulation...

  20. Transcutaneus electrical nerve stimulation for overactive bladder increases rectal motor activity in children: a randomized controlled study

    DEFF Research Database (Denmark)

    Jønsson, Iben; Hagstrøm, Søren; Siggaard, Charlotte

    Transcutaneus electrical nerve stimulation for overactive bladder increases rectal motor activity in children: a randomized controlled study......Transcutaneus electrical nerve stimulation for overactive bladder increases rectal motor activity in children: a randomized controlled study...

  1. Pharmacological and non-pharmacological treatment of obstructive hypertrophic cardiomyopathy.

    Science.gov (United States)

    Hidalgo, Luis F; Naidu, Srihari S; Aronow, Wilbert S

    2018-01-01

    Hypertrophic obstructive cardiomyopathy has been rising in prevalence, due to increased awareness and advanced imaging. For the symptomatic patient, pharmacological management remains an effective approach to the majority of patients with obstructive hypertrophic cardiomyopathy. However, a significant subset fails to improve sufficiently with medical therapy initially, or progressively becomes more symptomatic despite augmented medications over time. Most of the advances in the treatment of obstructive hypertrophic cardiomyopathy have therefore been made in the area of non-pharmacologic management, particularly septal reduction therapy. Both surgical myectomy and alcohol septal ablation have undergone iterative modifications that improve outcomes. Current guidelines support these therapies based on large observational studies, with choice of therapy based on a variety of factors but again based primarily on expert consensus opinion. Areas covered: This article reviews both pharmacological and non-pharmacological interventions to improve outflow tract obstruction and symptoms, and provides an algorithm for addressing the symptomatic obstructive patient. Expert commentary: Current options for hypertrophic cardiomyopathy allow the majority of patients to live their lives with no more than NYHA Class 2 heart failure symptoms. Treatment algorithms can add in identification of patients who may benefit from advanced therapies, and should be instituted routinely to improve care for the majority of patients with symptomatic hypertrophic cardiomyopathy.

  2. Deep brain stimulation increases impulsivity in two patients with obsessive-compulsive disorder.

    Science.gov (United States)

    Luigjes, Judy; Mantione, Mariska; van den Brink, Wim; Schuurman, P Richard; van den Munckhof, Pepijn; Denys, Damiaan

    2011-11-01

    Deep brain stimulation (DBS) is an adjustable, reversible, nondestructive neurosurgical intervention using implanted electrodes to deliver electrical pulses to areas in the brain. DBS has recently shown promising results as an experimental treatment of refractory obsessive-compulsive disorder (OCD). The novelty of the treatment requires careful observation of symptoms and possible side effects in patients. This case report describes two patients with treatment-refractory OCD in whom increased voltage of deep brain stimulation targeted at the nucleus accumbens increased impulsivity. Voltage increase of stimulation resulted in an immediate inflation of self-confidence, irritability and impulsive behaviour and was reversed only after lowering the voltage. The mechanisms behind DBS are not yet fully understood. Possibly, stimulation in the area of the nucleus accumbens affects the corticostriatal circuitry, which plays an important role in impulsivity. Location and amplitude of stimulation might be critical in inducing these behaviours. These two cases underline the importance of a careful clinical assessment of impulsive behaviours during DBS for OCD.

  3. Algal Cell Response to Pulsed Waved Stimulation and Its Application to Increase Algal Lipid Production

    Science.gov (United States)

    Savchenko, Oleksandra; Xing, Jida; Yang, Xiaoyan; Gu, Quanrong; Shaheen, Mohamed; Huang, Min; Yu, Xiaojian; Burrell, Robert; Patra, Prabir; Chen, Jie

    2017-02-01

    Generating renewable energy while sequestering CO2 using algae has recently attracted significant research attention, mostly directing towards biological methods such as systems biology, genetic engineering and bio-refining for optimizing algae strains. Other approaches focus on chemical screening to adjust culture conditions or culture media. We report for the first time the physiological changes of algal cells in response to a novel form of mechanical stimulation, or a pulsed wave at the frequency of 1.5 MHz and the duty cycle of 20%. We studied how the pulsed wave can further increase algal lipid production on top of existing biological and chemical methods. Two commonly used algal strains, fresh-water Chlorella vulgaris and seawater Tetraselmis chuii, were selected. We have performed the tests in shake flasks and 1 L spinner-flask bioreactors. Conventional Gravimetric measurements show that up to 20% increase for algal lipid could be achieved after 8 days of stimulation. The total electricity cost needed for the stimulations in a one-liter bioreactor is only one-tenth of a US penny. Gas liquid chromatography shows that the fatty acid composition remains unchanged after pulsed-wave stimulation. Scanning electron microscope results also suggest that pulsed wave stimulation induces shear stress and thus increases algal lipid production.

  4. Increasing the role of belief information in moral judgments by stimulating the right temporoparietal junction.

    Science.gov (United States)

    Sellaro, Roberta; Güroǧlu, Berna; Nitsche, Michael A; van den Wildenberg, Wery P M; Massaro, Valentina; Durieux, Jeffrey; Hommel, Bernhard; Colzato, Lorenza S

    2015-10-01

    Morality plays a vital role in our social life. A vast body of research has suggested that moral judgments rely on cognitive processes mediated by the right temporoparietal junction (rTPJ), an area thought to be involved in belief attribution. Here we assessed the role of the rTPJ in moral judgments directly by means of transcranial direct current stimulation (tDCS)--a non-invasive brain stimulation technique that, by applying a weak current to the scalp, allows modulating cortical excitability of the area being stimulated. Participants were randomly and equally assigned to receive anodal stimulation (to increase cortical excitability), cathodal stimulation (to decrease cortical excitability), or sham (placebo) stimulation over the rTPJ before completing a moral judgment task. Participants read stories in which protagonists produced either a negative or a neutral outcome based on either a negative or a neutral belief that they were causing harm or no harm, respectively. Results revealed a selective group difference when judging the moral permissibility of accidental harms (belief neutral, outcome negative), but not intentional harms (belief negative, outcome negative), attempted harms (belief negative, outcome neutral), or neutral acts (belief neutral, outcome neutral). Specifically, participants who received anodal stimulation assigned less blame to accidental harms compared to participants who received cathodal or sham stimulation. These results are consistent with previous findings showing that the degree of rTPJ activation reflects reliance on the agent's innocent intention. Crucially, our findings provide direct evidence supporting the critical role of the rTPJ in mediating belief attribution for moral judgment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Living with hypertrophic cardiomyopathy.

    Science.gov (United States)

    Subasic, Kim

    2013-12-01

    The purpose of this study is to provide an insider's account of what it is like to live with hypertrophic cardiomyopathy (HCM), a genetic cardiovascular illness that carries the risk for sudden cardiac death. This study aims to reveal how HCM impacts the family and guides the decision whether or not to pursue genetic testing, how the physical limitations associated with HCM alter being-in-the-world, and how HCM alters social relationships. Fifteen adults with HCM were recruited for a longitudinal, phenomenological, qualitative study through purposive sampling and word of mouth. A total of 45 interviews were conducted by the researcher at a time and place designated by the participant between August 2011 and January 2012. The first interview with each participant was conducted in person. While efforts were made to conduct all interviews in person, a total of three interviews were conducted by telephone as requested by three participants due to scheduling conflicts. Through methods of interpretive phenomenology, three audio-recorded, semistructured interviews occurred over the course of 3 months. Detailed narratives were solicited and transcribed verbatim. Methodological and analytical documentation was supported with the identification of key phrases, similar experiences, themes, and documentation of the rationale for decisions throughout the research process. Participation in genetic testing carries a multitude of personal, familial, financial, and emotional implications. The results of a genetic test elicited an emotional response regardless of whether the results were negative, positive, or inconclusive. Living with a potentially life-threatening illness altered identity, disrupted social relationships, and generated chronic fear and uncertainty. A new normal was re-ordered or transformed by the demands and limitations posed by HCM, and by the person's concerns, priorities, and the meaning of the illness. Results from this study underscore the need for healthcare

  6. Update on hypertrophic scar treatment

    Science.gov (United States)

    Rabello, Felipe Bettini; Souza, Cleyton Dias; Júnior, Jayme Adriano Farina

    2014-01-01

    Scar formation is a consequence of the wound healing process that occurs when body tissues are damaged by a physical injury. Hypertrophic scar/span>s and keloids are pathological scar/span>s resulting from abnormal responses to trauma and can be itchy and painful, causing serious functional and cosmetic disability. The current review will focus on the definition of hypertrophic scar/span>s, distinguishing them from keloids and on the various methods for treating hypertrophic scarring that have been described in the literature, including treatments with clearly proven efficiency and therapies with doubtful benefits. Numerous methods have been described for the treatment of abnormal scars, but to date, the optimal treatment method has not been established. This review will explore the differences between different types of nonsurgical management of hypertrophic scar/span>s, focusing on the indications, uses, mechanisms of action, associations and efficacies of the following therapies: silicone, pressure garments, onion extract, intralesional corticoid injections and bleomycin. PMID:25141117

  7. Familial idiopathic hypertrophic subaortic stenosis

    Directory of Open Access Journals (Sweden)

    Shah Lilam

    1979-01-01

    Full Text Available Echocardiographic features of idiopathic hypertrophic subaortic stenosis (IHSS are described. Systolic anterior motion (SAM of anterior mitral leaflet and asymetric septal hypertrophy (ASH are considered as the diagnostic criteria of IHSS. Effects of amyl nitrite and propranolol-a beta blocker are studied. Echocardio-graphic screening of family members revealed this as a case of fami-lial IHSS.

  8. PERCEPTION STIMULATION GROUP ACTIVITY THERAPY INCREASES E CHILDREN SELF ESTEEM AT PRISON

    Directory of Open Access Journals (Sweden)

    Ah. Yusuf

    2017-07-01

    Full Text Available Introduction: Prison is societal implementer unit which accommodate care and develop the delinquent children. It was recorded that 57% of children at Blitar Child Prison undergo some self concept problems such as low self esteem. This was caused by some factors such as society’s stigmatization toward criminals, development pattern and education, and less support from family. If the self esteem problem is not being overcome soon, the children may  fell useless, disable to control their self and recrime when they are back to society. The objective of this study was to analyze the influence of  GAT (Group Activity Therapy perception stimulation in increasing the children  self esteem at prison. Method:  A quasy experimental pre post control design was used in this study. Samples were recruited by using total sampling and there were 22 samples as on inclusion criteria. The independent variable was GAT perception stimulation and the dependent variable was increasing self esteem of these childen. Data were collected by using questionnare and analyzed by using Wilcoxon Signed Ranks Test and Mann Whitney U Test with the significance level α≤0.05.Result:  The result showed that controlled group has significance level was p=0.654, it is mean there was no self esteem change before and after GAT perception stimulation was given. Whereas treatment group has significance level was p=0.001, it revealed that  there was self esteem change before and after GAT perception stimulation was given. The result of Mann Whitney U Test showed p=0.000 which means was accepted. Discussion: It can be concluded that perception stimulation can increase the children self esteem at prison. Further studies are recommended to study the effect of GAT perception stimulation modified by skill therapy in increasing children self esteem in prison.

  9. Biological and Chemical Removal of Primary Cilia Affects Mechanical Activation of Chondrogenesis Markers in Chondroprogenitors and Hypertrophic Chondrocytes

    Directory of Open Access Journals (Sweden)

    Matthew E. Deren

    2016-02-01

    Full Text Available Chondroprogenitors and hypertrophic chondrocytes, which are the first and last stages of the chondrocyte differentiation process, respectively, are sensitive to mechanical signals. We hypothesize that the mechanical sensitivity of these cells depends on the cell surface primary cilia. To test this hypothesis, we removed the primary cilia by biological means with transfection with intraflagellar transport protein 88 (IFT88 siRNA or by chemical means with chloral hydrate treatment. Transfection of IFT88 siRNA significantly reduced the percentage of ciliated cells in both chondroprogenitor ATDC5 cells as well as primary hypertrophic chondrocytes. Cyclic loading (1 Hz, 10% matrix deformation of ATDC5 cells in three-dimensional (3D culture stimulates the mRNA levels of chondrogenesis marker Type II collagen (Col II, hypertrophic chondrocyte marker Type X collagen (Col X, and a molecular regulator of chondrogenesis and chondrocyte hypertrophy bone morphogenetic protein 2 (BMP-2. The reduction of ciliated chondroprogenitors abolishes mechanical stimulation of Col II, Col X, and BMP-2. In contrast, cyclic loading stimulates Col X mRNA levels in hypertrophic chondrocytes, but not those of Col II and BMP-2. Both biological and chemical reduction of ciliated hypertrophic chondrocytes reduced but failed to abolish mechanical stimulation of Col X mRNA levels. Thus, primary cilia play a major role in mechanical stimulation of chondrogenesis and chondrocyte hypertrophy in chondroprogenitor cells and at least a partial role in hypertrophic chondrocytes.

  10. Muscarinic receptor stimulation increases tolerance of rat salivary gland function to radiation damage

    NARCIS (Netherlands)

    Coppes, RP; Vissink, A; Zeilstra, LJW; Konings, AWT

    1997-01-01

    Purpose: To investigate if muscarinic receptor-stimulated activation of the PLC/PIP2 second messenger pathway prior to irradiation increases the radiotolerance of rat salivary gland. Materials and methods: Rats were treated with pilocarpine, methacholine, reserpine, methacholine plus reserpine, or

  11. ANODAL TRANSCRANIAL DIRECT CURRENT STIMULATION (TDCS) INCREASES ISOMETRIC STRENGTH OF SHOULDER ROTATORS MUSCLES IN HANDBALL PLAYERS.

    Science.gov (United States)

    Hazime, Fuad Ahmad; da Cunha, Ronaldo Alves; Soliaman, Renato Rozenblit; Romancini, Ana Clara Bezerra; Pochini, Alberto de Castro; Ejnisman, Benno; Baptista, Abrahão Fontes

    2017-06-01

    Weakness of the rotator cuff muscles can lead to imbalances in the strength of shoulder external and internal rotators, change the biomechanics of the glenohumeral joint and predispose an athlete to injury. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that has demonstrated promising results in a variety of health conditions. However few studies addressed its potential approach in the realm of athletics. The purpose of this study was to investigate if transcranial direct current stimulation (tDCS) technique increases the isometric muscle strength of shoulder external and internal rotators in handball athletes. Randomized, double-blind, placebo-controlled, crossover study. Eight female handball players aged between 17 and 21 years (Mean=19.65; SD=2.55) with 7.1 ± 4.8 years of experience in training, participating in regional and national competitions were recruited. Maximal voluntary isometric contraction (MVIC) of shoulder external and internal rotator muscles was evaluated during and after 30 and 60 minutes post one session of anodal and sham current (2mA; 0.057mA/cm2) with a one-week interval between stimulations. Compared to baseline, MVIC of shoulder external and internal rotators significantly increased after real but not sham tDCS. Between-group differences were observed for external and internal rotator muscles. Maximal voluntary isometric contraction of external rotation increased significantly during tDCS, and 30 and 60 minutes post-tDCS for real tDCS compared to that for sham tDCS. For internal rotation MVIC increased significantly during and 60 minutes post-tDCS. The results indicate that transcranial direct current stimulation temporarily increases maximal isometric contractions of the internal and external rotators of the shoulder in handball players. 2.

  12. Non-invasive brain stimulation targeting the right fusiform gyrus selectively increases working memory for faces.

    Science.gov (United States)

    Brunyé, Tad T; Moran, Joseph M; Holmes, Amanda; Mahoney, Caroline R; Taylor, Holly A

    2017-04-01

    The human extrastriate cortex contains a region critically involved in face detection and memory, the right fusiform gyrus. The present study evaluated whether transcranial direct current stimulation (tDCS) targeting this anatomical region would selectively influence memory for faces versus non-face objects (houses). Anodal tDCS targeted the right fusiform gyrus (Brodmann's Area 37), with the anode at electrode site PO10, and cathode at FP2. Two stimulation conditions were compared in a repeated-measures design: 0.5mA versus 1.5mA intensity; a separate control group received no stimulation. Participants completed a working memory task for face and house stimuli, varying in memory load from 1 to 4 items. Individual differences measures assessed trait-based differences in facial recognition skills. Results showed 1.5mA intensity stimulation (versus 0.5mA and control) increased performance at high memory loads, but only with faces. Lower overall working memory capacity predicted a positive impact of tDCS. Results provide support for the notion of functional specialization of the right fusiform regions for maintaining face (but not non-face object) stimuli in working memory, and further suggest that low intensity electrical stimulation of this region may enhance demanding face working memory performance particularly in those with relatively poor baseline working memory skills. Published by Elsevier Inc.

  13. Upregulation of TRPC1 contributes to contractile function in isoproterenol-induced hypertrophic myocardium of rat.

    Science.gov (United States)

    Chen, Mo-Si; Xiao, Jun-Hua; Wang, Yong; Xu, Bo-Ming; Gao, Lu; Wang, Jia-Ling

    2013-01-01

    The transient receptor potential canonical channel 1 (TRPC1) is a crucial component of the stretch-activated ion channels (SACs). The objective of this research was to demonstrate the contribution of TRPC1 in maintaining cardiac contractile function in the hypertrophic myocardium. Hypertrophic rat hearts were induced by injecting isoproterenol intraperitoneally, and the expressions of TRPC1/3/6 and Na(+)/Ca(2+) exchanger 1 (NCX1) proteins were analyzed by Western blot. The intracellular calcium images, the action potential of myocardium, the length-dependent contractile force of ventricle muscle and the cardiac output of isolated heart were investigated. The expression of TRPC1 was increased in the hypertrophic myocardium. After being stretched, the ascendant amplitude of the increase in the intracellular calcium ion concentration ([Ca(2+)]i) in the hypertrophic myocardium was higher than that in the normal myocardium. The increase of the APD50 and the amplitude of the membrane potential depolarization were more significant in the hypertrophic myocardium after the activation of SACs. When the heart preparations were perfused with Tyrode's solution, there was no difference in the cardiac systolic function between the cardiac hypertrophy group and the control group. Gadolinium, a SACs blocker, reduced the length-dependent contractile force and suppressed the ascending limb of the Frank-Starling curves in the hypertrophic heart. The upregulation of TRPC1 contributes to the contractile function in the hypertrophic myocardium by increasing [Ca(2+)]i through the SACs. © 2013 S. Karger AG, Basel

  14. Symmetric Dimethylarginine in Cats with Hypertrophic Cardiomyopathy and Diabetes Mellitus

    DEFF Research Database (Denmark)

    Langhorn, R.; Kieler, I. N.; Koch, J.

    2018-01-01

    Background: Symmetric dimethylarginine (SDMA) has been increasingly used as a marker of early chronic kidney disease (CKD) in cats, but little is known about the influence of comorbidities on SDMA in this species. Hypothesis: Hypertrophic cardiomyopathy (HCM) and diabetes mellitus (DM), independe...

  15. Transpinal and transcortical stimulation alter corticospinal excitability and increase spinal output.

    Directory of Open Access Journals (Sweden)

    Maria Knikou

    Full Text Available The objective of this study was to assess changes in corticospinal excitability and spinal output following noninvasive transpinal and transcortical stimulation in humans. The size of the motor evoked potentials (MEPs, induced by transcranial magnetic stimulation (TMS and recorded from the right plantar flexor and extensor muscles, was assessed following transcutaneous electric stimulation of the spine (tsESS over the thoracolumbar region at conditioning-test (C-T intervals that ranged from negative 50 to positive 50 ms. The size of the transpinal evoked potentials (TEPs, induced by tsESS and recorded from the right and left plantar flexor and extensor muscles, was assessed following TMS over the left primary motor cortex at 0.7 and at 1.1× MEP resting threshold at C-T intervals that ranged from negative 50 to positive 50 ms. The recruitment curves of MEPs and TEPs had a similar shape, and statistically significant differences between the sigmoid function parameters of MEPs and TEPs were not found. Anodal tsESS resulted in early MEP depression followed by long-latency MEP facilitation of both ankle plantar flexors and extensors. TEPs of ankle plantar flexors and extensors were increased regardless TMS intensity level. Subthreshold and suprathreshold TMS induced short-latency TEP facilitation that was larger in the TEPs ipsilateral to TMS. Noninvasive transpinal stimulation affected ipsilateral and contralateral actions of corticospinal neurons, while corticocortical and corticospinal descending volleys increased TEPs in both limbs. Transpinal and transcortical stimulation is a noninvasive neuromodulation method that alters corticospinal excitability and increases motor output of multiple spinal segments in humans.

  16. Ovarian stimulation with follicle-stimulating hormone under increasing or minimal concentration of progesterone in dairy cows.

    Science.gov (United States)

    El-Sherry, T M; Matsui, M; Kida, K; Miyamoto, A; Megahed, G A; Shehata, S H; Miyake, Y-I

    2010-03-01

    The objective of this study was to investigate the effect of the presence or absence of Corpus luteum (CL) on the follicular population during superstimulation in dairy cows (Holstein-Friesian cattle). Animals were divided into two groups as follows: (1) Growing CL group (G1): Cows (n=7) received a total dose of 28 Armour units (AU) follicle-stimulating hormone (FSH) through the first 4 d (twice daily) after spontaneous ovulation (Day 0). (2) CL Absence group (G2): Cows (n=10) received prostaglandin F(2alpha) (PGF(2alpha)) at 9 or 10 d after ovulation. After 36h, all the follicles (larger than 5mm) were aspirated (Day 0). The FSH treatment started 24h after aspiration and continued for 4 d. The number of small (3 to or = 8mm) follicles was examined on Days 1, 3, and 5 in all groups. Blood samples were collected daily for 5 d, and progesterone (P(4)), estradiol (E(2)), insulin-like growth factor-1 (IGF-1), and growth hormone (GH) in plasma were measured by enzyme immunoassays. The results showed that in G1, the P(4) level increased gradually from 0.5 ng/mL at Day 1 to 2 ng/mL at Day 5, whereas in G2, the P(4) level was completely below 0.5 ng/mL. All cows of the G2 group showed an increase of E(2) at Day 3 or Day 4 followed by an increase of IGF-1 within 24h, while GH increased concomitantly with the E(2) increase in 8 of 10 trials. On the other hand, cows of the G1 group showed neither E(2) nor IGF-1 increase. Moreover, at the end of the treatment, the number of follicles in the G2 group was significantly increased compared with that of the G1 group (22.8+/-2.0 vs. 11.6+/-2.0). In conclusion, low P(4) level during FSH treatment enhanced multiple follicular growth and E(2) secretion, which was followed by increase of IGF-1 and GH. Therefore, the absence of the CL may play a critical role in the superovulation response by controlling the number of growing follicles. Copyright 2010 Elsevier Inc. All rights reserved.

  17. Pairing voluntary movement and muscle-located electrical stimulation increases cortical excitability

    Directory of Open Access Journals (Sweden)

    Mads Jochumsen

    2016-09-01

    Full Text Available Learning new motor skills has been correlated with increased cortical excitability. In this study, different location of electrical stimulation (ES, nerve or muscle, was paired with voluntary movement to investigate if ES paired with voluntary movement a would increase the excitability of cortical projections to tibialis anterior and b if stimulation location mattered. Cortical excitability changes were quantified using motor evoked potentials (MEPs elicited by transcranial magnetic stimulation at varying intensities during four conditions. Twelve healthy subjects performed 50 dorsiflexions at the ankle during nerve or muscle ES at motor threshold. ES alone was delivered 50 times and the movement was performed 50 times. A significant increase in the excitability from pre- to post-intervention (P=0.0061 and pre- to 30 minutes post-intervention (P=0.017 measurements was observed when voluntary movement was paired with muscle ES located at tibialis anterior. An increase of 50±57% and 28±54% in the maximum MEPs was obtained for voluntary movement paired with muscle-located and nerve-located ES, respectively. The maximum MEPs for voluntary movement alone and muscle-located ES alone were -5±28% and 2±42%, respectively. Pairing voluntary movement with muscle-located ES increases excitability of corticospinal projections of tibialis anterior in healthy participants. This finding suggests that active participation during muscle-located ES protocols increases cortical excitability to a greater extent than stimulation alone. The next stage of this research is to investigate the effect in people with stroke. The results may have implications for motor recovery in patients with motor impairments following neurological injury.

  18. Anodal transcranial direct current stimulation of the motor cortex increases cortical voluntary activation and neural plasticity.

    Science.gov (United States)

    Frazer, Ashlyn; Williams, Jacqueline; Spittles, Michael; Rantalainen, Timo; Kidgell, Dawson

    2016-11-01

    We examined the cumulative effect of 4 consecutive bouts of noninvasive brain stimulation on corticospinal plasticity and motor performance, and whether these responses were influenced by the brain-derived neurotrophic factor (BDNF) polymorphism. In a randomized double-blinded cross-over design, changes in strength and indices of corticospinal plasticity were analyzed in 14 adults who were exposed to 4 consecutive sessions of anodal and sham transcranial direct current stimulation (tDCS). Participants also undertook a blood sample for BDNF genotyping (N = 13). We observed a significant increase in isometric wrist flexor strength with transcranial magnetic stimulation revealing increased corticospinal excitability, decreased silent period duration, and increased cortical voluntary activation compared with sham tDCS. The results show that 4 consecutive sessions of anodal tDCS increased cortical voluntary activation manifested as an improvement in strength. Induction of corticospinal plasticity appears to be influenced by the BDNF polymorphism. Muscle Nerve 54: 903-913, 2016. © 2016 Wiley Periodicals, Inc.

  19. Healthy subjects with a family history of alcoholism show increased stimulative subjective effects of alcohol.

    Science.gov (United States)

    Söderpalm Gordh, Anna H V; Söderpalm, Bo

    2011-08-01

    Research has shown that subjects with a family history positive (FHP) of alcoholism are at increased risk for alcoholism and that this group reacts differently to alcohol than family history negative (FHN) subjects. These different levels of sensitivity may make FHP persons more likely to consume alcohol. Here, we tested the hypothesis that subjects FHP for type 1 alcoholism (according to Cloninger) are more sensitive than control subjects to the stimulative, properties of alcohol following a single moderate dose of alcohol. Fifty-one healthy men and women (22 FHP and 29 FHN) participated in 2 laboratory sessions, in which they consumed a beverage containing ethanol (0.6 g/kg in juice) or placebo (juice alone) in a randomized order. Primary dependent measures were self-report questionnaires of mood states. Subjects with family history of type 1 alcoholism showed increased stimulative responses and an elevated positive mood state after ethanol compared to controls. At this moderate dose, ethanol increased stimulative subjective responses in individuals who were "family history positive." This enhanced sensitivity could motivate to exaggerated drinking and thereby increase the risk for developing alcoholism. Copyright © 2011 by the Research Society on Alcoholism.

  20. Apical hypertrophic cardiomyopathy: clinical and metabolic studies.

    Science.gov (United States)

    Bertrand, M E; Tilmant, P Y; Lablanche, J M; Thieuleux, F A

    1983-11-01

    Among the hypertrophic non-obstructive cardiomyopathies, a particular group of patients with concentric apical hypertrophy can be described. We studied seven patients (five men and two women) who underwent heart catheterization because they had giant negative T waves in the precordial leads. M-mode and two-dimensional echocardiograms revealed no obstruction within the outflow tract of the ventricle. Coronary angiography was normal in all cases. None of these patients demonstrated any significant peak systolic pressure gradient in the outflow tract. A characteristic spade-like configuration (concentric apical hypertrophy) was observed in the right anterior oblique ventriculogram at end diastole. The apical thickness reached 17.2 +/- 0.85 mm and was significantly greater than mid-anterior wall thickness (9.8 +/- 2.14 mm). In five cases, atrial pacing with coronary arterial and venous lactate sampling revealed abnormalities in myocardial metabolism. With a mean follow up of 43 months, three patients remain asymptomatic and one had heart failure. ECG abnormalities were unchanged and echocardiograms showed an increase of the septal and posterior wall thickness, suggesting a transformation in concentric diffuse hypertrophic cardiomyopathy.

  1. Metformin increases insulin-stimulated glucose transport in insulin-resistant human skeletal muscle.

    Science.gov (United States)

    Galuska, D; Zierath, J; Thörne, A; Sonnenfeld, T; Wallberg-Henriksson, H

    1991-05-01

    The effect of metformin (0.1 mM) on glucose transport was investigated in healthy control and in insulin-resistant human skeletal muscle. Muscle samples (200-400 mg) were obtained from the rectus abdominis muscle (abdominal surgery) or from the vastus lateralis portion of the quadriceps femoris muscle (open biopsy technique) from 8 healthy controls (age 38 +/- 4 yrs, BMI 23 +/- 1) and from 6 insulin-resistant subjects (age 53 +/- 5 yrs, BMI 30 +/- 2). Metformin had no effect on basal or insulin-stimulated (100 microU/ml) 3-0-methylglucose transport in incubated muscle strips from healthy subjects. Muscle tissue from the insulin resistant group did not respond to 100 microU/ml of insulin (0.73 +/- 0.17 for basal and 0.81 +/- 0.22 mumol x ml-1 x h-1 for insulin-stimulation, NS). Basal glucose transport was unaffected by metformin, whereas insulin-stimulated (100 microU/ml) glucose transport was increased by 63% in the insulin-resistant muscles (0.73 +/- 0.17 in the absence vs 1.19 +/- 0.18 mumol x ml-1 x h-1 in the presence of metformin, p less than 0.05). In conclusion, metformin abolishes insulin-resistance in human skeletal muscle by normalizing insulin-stimulated glucose transport accross the muscle cell membrane. The mechanism for this effect remains to be elucidated.

  2. Multi-electrode stimulation in somatosensory cortex increases probability of detection

    Science.gov (United States)

    Zaaimi, Boubker; Ruiz-Torres, Ricardo; Solla, Sara A.; Miller, Lee E.

    2013-10-01

    Objective. Brain machine interfaces (BMIs) that decode control signals from motor cortex have developed tremendously in the past decade, but virtually all rely exclusively on vision to provide feedback. There is now increasing interest in developing an afferent interface to replace natural somatosensation, much as the cochlear implant has done for the sense of hearing. Preliminary experiments toward a somatosensory neuroprosthesis have mostly addressed the sense of touch, but proprioception, the sense of limb position and movement, is also critical for the control of movement. However, proprioceptive areas of cortex lack the precise somatotopy of tactile areas. We showed previously that there is only a weak tendency for neighboring neurons in area 2 to signal similar directions of hand movement. Consequently, stimulation with the relatively large currents used in many studies is likely to activate a rather heterogeneous set of neurons. Approach. Here, we have compared the effect of single-electrode stimulation at subthreshold levels to the effect of stimulating as many as seven electrodes in combination. Main results. We found a mean enhancement in the sensitivity to the stimulus (d‧) of 0.17 for pairs compared to individual electrodes (an increase of roughly 30%), and an increase of 2.5 for groups of seven electrodes (260%). Significance. We propose that a proprioceptive interface made up of several hundred electrodes may yield safer, more effective sensation than a BMI using fewer electrodes and larger currents.

  3. Improving Cycling Performance: Transcranial Direct Current Stimulation Increases Time to Exhaustion in Cycling.

    Directory of Open Access Journals (Sweden)

    Marcelo Vitor-Costa

    Full Text Available The central nervous system seems to have an important role in fatigue and exercise tolerance. Novel noninvasive techniques of neuromodulation can provide insights on the relationship between brain function and exercise performance. The purpose of this study was to determine the effects of transcranial direct current stimulation (tDCS on physical performance and physiological and perceptual variables with regard to fatigue and exercise tolerance. Eleven physically active subjects participated in an incremental test on a cycle simulator to define peak power output. During 3 visits, the subjects experienced 3 stimulation conditions (anodal, cathodal, or sham tDCS-with an interval of at least 48 h between conditions in a randomized, counterbalanced order to measure the effects of tDCS on time to exhaustion at 80% of peak power. Stimulation was administered before each test over 13 min at a current intensity of 2.0 mA. In each session, the Brunel Mood State questionnaire was given twice: after stimulation and after the time-to-exhaustion test. Further, during the tests, the electromyographic activity of the vastus lateralis and rectus femoris muscles, perceived exertion, and heart rate were recorded. RM-ANOVA showed that the subjects performed better during anodal primary motor cortex stimulation (491 ± 100 s compared with cathodal stimulation (443 ± 11 s and sham (407 ± 69 s. No significant difference was observed between the cathodal and sham conditions. The effect sizes confirmed the greater effect of anodal M1 tDCS (anodal x cathodal = 0.47; anodal x sham = 0.77; and cathodal x sham = 0.29. Magnitude-based inference suggested the anodal condition to be positive versus the cathodal and sham conditions. There were no differences among the three stimulation conditions in RPE (p = 0.07 or heart rate (p = 0.73. However, as hypothesized, RM- ANOVA revealed a main effect of time for the two variables (RPE and HR: p < 0.001. EMG activity also did not

  4. Squamous Cell Carcinoma Arising in Hypertrophic Lichen Planus: A Review and Analysis of 38 Cases.

    Science.gov (United States)

    Knackstedt, Thomas J; Collins, Lindsey K; Li, Zhongze; Yan, Shaofeng; Samie, Faramarz H

    2015-12-01

    Hypertrophic lichen planus is a chronic variant of lichen planus with controversial malignant association. To describe and analyze the relationship of squamous cell carcinoma (SCC) and hypertrophic lichen planus. A retrospective chart review of patients with hypertrophic lichen planus and SCC was performed at the authors' institution. Thereafter, scientific databases were searched for articles reporting cases of SCC arising in hypertrophic lichen planus. Patient demographics, immune status, lichen planus features, and SCC data points were extracted for each patient and evaluated. Thirty-eight cases of SCC in hypertrophic lichen planus occurred in 16 women, average age: 61.4, and 22 men, average age: 51.3, after a lag time of 88 days to 40 years. Squamous cell carcinoma was uniformly located on the lower extremity. Men had larger SCC than women (p = .027) and a significantly longer lag time to SCC development (p = .002). Long lag time was associated with a smaller SCC size (p = .032). In the past, hypertrophic lichen planus and SCC have been considered isolated diseases. Based on an increasing number of cases, the association between hypertrophic lichen planus and keratinocyte malignancies warrants surveillance.

  5. Structural determinants for the ouabain-stimulated increase in Na-K ATPase activity.

    Science.gov (United States)

    Khundmiri, Syed J; Salyer, Sarah A; Farmer, Brandon; Qipshidze-Kelm, Natia; Murray, Rebecca D; Clark, Barbara J; Xie, Zijian; Pressley, Thomas A; Lederer, Eleanor D

    2014-06-01

    Recent studies suggest that at low concentrations, ouabain increases Na-K ATPase and NHE1 activity and activates the Src signaling cascade in proximal tubule cells. Our laboratory demonstrated that low concentrations of ouabain increase blood pressure in rats. We hypothesize that ouabain-induced increase in blood pressure and Na-K ATPase activity requires NHE1 activity and association. To test this hypothesis we treated rats with ouabain (1μgkg body wt(-1)day(-1)) for 9days in the presence or absence of the NHE1 inhibitor, zoniporide. Ouabain stimulated a significant increase in blood pressure which was prevented by zoniporide. Using NHE1-expressing Human Kidney cells 2 (HK2), 8 (HK8) and 11 (HK11) and Mouse Kidney cells from Wild type (WT) and NHE1 knock-out mice (SWE) cell lines, we show that ouabain stimulated Na-K ATPase activity and surface expression in a Src-dependent manner in NHE1-expressing cells but not in NHE1-deplete cells. Zoniporide prevented ouabain-induced stimulation of (86)Rb uptake in the NHE1-expressing cells. FRET and TIRF microscopy showed that ouabain increased association between GFP-NHE1 and mCherry-Na-K ATPase transfected into NHE1-deficient SWE cells. Mutational analysis demonstrated that the caveolin binding motif (CBM) of Na-K ATPase α1 is required for translocation of both Na-K ATPase α1 and NHE1 to the basolateral membrane. Mutations in activity or scaffold domains of NHE1 resulted in loss of ouabain-mediated regulation of Na-K ATPase. These results support that NHE1 is required for the ouabain-induced increase in blood pressure, and that the caveolin binding motif of Na-K ATPase α1 as well as the activity and scaffolding domains of NHE1 are required for their functional association. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Transcranial direct-current stimulation increases extracellular dopamine levels in the rat striatum

    Science.gov (United States)

    Tanaka, Tomoko; Takano, Yuji; Tanaka, Satoshi; Hironaka, Naoyuki; Kobayashi, Kazuto; Hanakawa, Takashi; Watanabe, Katsumi; Honda, Manabu

    2013-01-01

    Background: Transcranial direct-current stimulation (tDCS) is a non-invasive procedure that achieves polarity-dependent modulation of neuronal membrane potentials. It has recently been used as a functional intervention technique for the treatment of psychiatric and neurological diseases; however, its neuronal mechanisms have not been fully investigated in vivo. Objective/Hypothesis: To investigate whether the application of cathodal or anodal tDCS affects extracellular dopamine and serotonin levels in the rat striatum. Methods: Stimulation and in vivo microdialysis were carried out under urethane anesthesia, and microdialysis probes were slowly inserted into the striatum. After the collection of baseline fractions in the rat striatum, cathodal or anodal tDCS was applied continuously for 10 min with a current intensity of 800 μA from an electrode placed on the skin of the scalp. Dialysis samples were collected every 10 min until at least 400 min after the onset of stimulation. Results: Following the application of cathodal, but not anodal, tDCS for 10 min, extracellular dopamine levels increased for more than 400 min in the striatum. There were no significant changes in extracellular serotonin levels. Conclusion: These findings suggest that tDCS has a direct and/or indirect effect on the dopaminergic system in the rat basal ganglia. PMID:23596399

  7. Hypertrophic osteoarthropathy in primary liver rhabdomyosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Geary, T.R.; Maclennan, A.C.; Irwin, G.J. [Radiology Dept., Royal Hospital for Sick Children, Yorkhill NHS Trust, Glasgow (United Kingdom)

    2004-03-01

    Hypertrophic osteoarthropathy is a well-documented paraneoplastic phenomenon in adults. It is a rare, but important finding in children with malignant disease as it can indicate prognosis. We present a case of hypertrophic osteoarthropathy associated with primary liver rhabdomyosarcoma in a 14-year-old boy. (orig.)

  8. Idiopathic hypertrophic pachymeningitis presenting with occipital ...

    African Journals Online (AJOL)

    Abstract: Background: Although occipital neuralgia is usually caused by degenerative arthropathy, nearly 20 other aetiologies may lead to this condition. Methods: We present the first case report of hypertrophic pachymeningitis revealed by isolated occipital neuralgia. Results and conclusions: Idiopathic hypertrophic ...

  9. Idiopathic hypertrophic pachymeningitis presenting with occipital ...

    African Journals Online (AJOL)

    Background: Although occipital neuralgia is usually caused by degenerative arthropathy, nearly 20 other aetiologies may lead to this condition. Methods: We present the first case report of hypertrophic pachymeningitis revealed by isolated occipital neuralgia. Results and conclusions: Idiopathic hypertrophic ...

  10. Nicotine increases stress-induced serotonin release by stimulating nicotinic acetylcholine receptor in rat striatum.

    Science.gov (United States)

    Takahashi, H; Takada, Y; Nagai, N; Urano, T; Takada, A

    1998-03-01

    We used a microdialysis technique to analyze the effects of footshock stress on the release of serotonin (5-hydroxytryptamine: 5-HT) in the striatum or prefrontal cortex (PFC) in rats that were pretreated with nicotine. Neither nicotine administration alone nor stress application alone changed 5-HT release. During stress application, however, both chronic nicotine administration and local infusion of nicotine to the striatum significantly increased 5-HT release in the striatum, though not in the PFC. These increases in 5-HT release were eradicated by a local infusion of mecamylamine. Release of 5-HT increased in the striatum during stress application when nicotine was injected to the striatum, while nicotinic injection to the dorsal raphe nucleus did not increase 5-HT release in the striatum. The present study demonstrates that nicotine induced a release of 5-HT upon stress application by stimulating presynaptic nicotinic receptors in the striatum.

  11. Subendocardial ischemia in hypertrophic cardiomyopathy.

    Science.gov (United States)

    Kawasaki, Tatsuya; Sugihara, Hiroki

    2014-02-01

    Hypertrophic cardiomyopathy (HCM) patients often develop subendocardial ischemia in the left ventricle without atherosclerotic coronary stenosis. Myocardial ischemia plays an important role in the pathophysiology of HCM, but diagnostic techniques for the detection of subendocardial ischemia have not been widely available. We developed specific techniques to quantify subendocardial ischemia on stress scintigraphy, and have compared the results with various clinical features in patients with HCM. This article reviews our understanding of subendocardial ischemia in HCM based on more than 20 years of experience. Copyright © 2013 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  12. Increased probability of repetitive spinal motoneuron activation by transcranial magnetic stimulation after muscle fatigue in healthy subjects

    DEFF Research Database (Denmark)

    Andersen, Birgit; Felding, Ulrik Ascanius; Krarup, Christian

    2012-01-01

    Triple stimulation technique (TST) has previously shown that transcranial magnetic stimulation (TMS) fails to activate a proportion of spinal motoneurons (MNs) during motor fatigue. The TST response depression without attenuation of the conventional motor evoked potential suggested increased prob...... the muscle is fatigued. Repetitive MN firing may provide an adaptive mechanism to maintain motor unit activation and task performance during sustained voluntary activity.......Triple stimulation technique (TST) has previously shown that transcranial magnetic stimulation (TMS) fails to activate a proportion of spinal motoneurons (MNs) during motor fatigue. The TST response depression without attenuation of the conventional motor evoked potential suggested increased...... probability of repetitive spinal MN activation during exercise even if some MNs failed to discharge by the brain stimulus. Here we used a modified TST (Quadruple stimulation; QuadS and Quintuple stimulation; QuintS) to examine the influence of fatiguing exercise on second and third MN discharges after...

  13. Deep brain stimulation of the ventral striatum increases BDNF in the fear extinction circuit

    Directory of Open Access Journals (Sweden)

    Fabricio H Do-Monte

    2013-08-01

    Full Text Available Deep brain stimulation (DBS of the ventral capsule/ventral striatum (VC/VS reduces the symptoms of treatment-resistant obsessive compulsive disorder (OCD, and improves response to extinction-based therapies. We recently reported that DBS-like stimulation of a rat homologue of VC/VS, the dorsal-VS, reduced conditioned fear and enhanced extinction memory (Rodriguez-Romaguera et al, 2012. In contrast, DBS of the ventral-VS had the opposite effects. To examine possible mechanisms, we assessed the effects of VS DBS on the expression of the neural activity marker Fos and brain-derived neurotrophic factor (BDNF, a key mediator of extinction plasticity in prefrontal-amygdala circuits. Consistent with decreased fear expression, DBS of dorsal-VS increased Fos expression in prelimbic and infralimbic prefrontal cortices and in the lateral division of the central nucleus of amygdala, an area that inhibits amygdala output. Consistent with improved extinction memory, we found that DBS of dorsal-VS, but not ventral-VS, increased neuronal BDNF expression in prelimbic and infralimbic prefrontal cortices. These rodent findings are consistent with the idea that clinical DBS of VC/VS may augment fear extinction through an increase in BDNF expression.

  14. Ghrelin stimulation by hypothalamic-pituitary-adrenal axis activation depends on increasing cortisol levels.

    Science.gov (United States)

    Azzam, I; Gilad, S; Limor, R; Stern, N; Greenman, Y

    2017-11-01

    Ghrelin plasma concentration increases in parallel to cortisol after a standardized psychological stress in humans, but the physiological basis of this interaction is unknown. We aimed to elucidate this question by studying the ghrelin response to pharmacological manipulation of the hypothalamic-pituitary-adrenal (HPA) axis. Six lean, healthy male volunteers were examined under four experimental conditions. Blood samples were collected every 30 min for two sequential periods of two hours. Initially, a baseline period was followed by intravenous injection of a synthetic analog of ACTH (250 μg). Subsequently, a single dose of metyrapone was administered at midnight and in the following morning, blood samples were collected for 2 h, followed by an intravenous injection of hydrocortisone (100 mg) with continued sampling. We show that increased cortisol serum levels secondary to ACTH stimulation or hydrocortisone administration are positively associated with plasma ghrelin levels, whereas central stimulation of the HPA axis by blocking cortisol synthesis with metyrapone is associated with decreased plasma ghrelin levels. Collectively, this suggests that HPA-axis-mediated elevations in ghrelin plasma concentration require increased peripheral cortisol levels, independent of central elevation of ACTH and possibly CRH levels. © 2017 The authors.

  15. Boron stem infusions stimulate soybean yield by increasing pods on lateral branches.

    Science.gov (United States)

    Schon, M K; Blevins, D G

    1987-08-01

    Studies were carried out to determine if supplemental B (H(3)BO(3)) and Ca (CaCl(2)) injected via a stem infusion technique into soybeans could stimulate yield by increasing pods on lateral branches, seed number, and overall seed yield. Boron treatments caused a significant 84.8% increase in the number of lateral pods/plant and a 17.6% increase in total seed weight/plant. This corresponded to a seed yield of 4170 kilograms per hectare in the B-treated plants compared to 3540 kilograms per hectare in the injected control plants, indicating that B deficiency may have been a factor in limiting yield of control plants. Ca treatments tended to accentuate the negative yield effects of apparent B deficiency.

  16. Psychotherapeutical effects of stimulate positive connotation in the increase of forgiveness

    Directory of Open Access Journals (Sweden)

    Andrés Fernando López Pell

    2009-10-01

    Full Text Available This work presents different aspects that have been related to the aptitude to forgive, emphasizing its importance for the psychotherapeutic practice in order to promote an increase of such capacity. Existing empirical evidence tends to relate forgiveness to emotional, physical and psychological well-being of the persons, and shows that the way of providing sense to the experiences influences the process of forgiveness. An alternative to increase the aptitude to forgive is proposed and results of an experimental study with 60 patients demonstrate the psychotherapeutic effects of stimulating positive connotation in the increase of forgiveness. The independent variable was the type of psychotherapeutic approach applied and the dependant variables were measured with the Aptitude to Forgive Scale (CAPER that evaluates the general predisposition of a subject to forgive, across four independent constructs: a Self, b Others, c Situation, and d Beliefs.

  17. Transcranial direct current stimulation transiently increases the blood-brain barrier solute permeability in vivo

    Science.gov (United States)

    Shin, Da Wi; Khadka, Niranjan; Fan, Jie; Bikson, Marom; Fu, Bingmei M.

    2016-03-01

    Transcranial Direct Current Stimulation (tDCS) is a non-invasive electrical stimulation technique investigated for a broad range of medical and performance indications. Whereas prior studies have focused exclusively on direct neuron polarization, our hypothesis is that tDCS directly modulates endothelial cells leading to transient changes in blood-brain-barrier (BBB) permeability (P) that are highly meaningful for neuronal activity. For this, we developed state-of-the-art imaging and animal models to quantify P to various sized solutes after tDCS treatment. tDCS was administered using a constant current stimulator to deliver a 1mA current to the right frontal cortex of rat (approximately 2 mm posterior to bregma and 2 mm right to sagittal suture) to obtain similar physiological outcome as that in the human tDCS application studies. Sodium fluorescein (MW=376), or FITC-dextrans (20K and 70K), in 1% BSA mammalian Ringer was injected into the rat (SD, 250-300g) cerebral circulation via the ipsilateral carotid artery by a syringe pump at a constant rate of ~3 ml/min. To determine P, multiphoton microscopy with 800-850 nm wavelength laser was applied to take the images from the region of interest (ROI) with proper microvessels, which are 100-200 micron below the pia mater. It shows that the relative increase in P is about 8-fold for small solute, sodium fluorescein, ~35-fold for both intermediate sized (Dex-20k) and large (Dex-70k) solutes, 10 min after 20 min tDCS pretreatment. All of the increased permeability returns to the control after 20 min post treatment. The results confirmed our hypothesis.

  18. Insulin stimulation of glucose transport activity in rat skeletal muscle: increase in cell surface GLUT4 as assessed by photolabelling.

    OpenAIRE

    Wilson, C. M.; Cushman, S W

    1994-01-01

    We have used a photoaffinity label to quantify cell surface GLUT4 glucose transporters in isolated rat soleus muscles. In this system, insulin stimulated an 8.6-fold increase in 3-O-methylglucose glucose transport, while photolabelled GLUT4 increased 8-fold. These results demonstrate that the insulin-stimulated increase in glucose transport activity in skeletal muscle can be accounted for by an increase in surface-accessible GLUT4 content.

  19. Valporic acid enhances the Atrial Natriuretic Peptide (ANP) mediated anti-hypertrophic activity by modulating the Npr1 gene transcription in H9c2 cells in vitro.

    Science.gov (United States)

    Manivasagam, Senthamizharasi; Velusamy, Tamilselvi; Sowndharajan, Boopathi; Chandrasekar, Navvi; Dhanusu, Suresh; Vellaichamy, Elangovan

    2017-10-15

    The present study was aimed to determine whether stimulating Npr1 gene activity using Valporic acid (VA), a small short chain fatty acid molecule can enhance ANP mediated anti-hypertrophic activity in isoproterenol (ISO) - treated H9c2 cells in vitro. H9c2 cells were treated with ISO (10 -5 M) and co-treated with VA (10 -5 M) in the presence and absence of ANP (10 -8 M), for 48h. ATRA (10 -5 M) was used as a positive inducer of Npr1 gene transcription. The mRNA expression of Npr1 and PKG-I genes, proto-oncogenes (c-fos, c-jun and c-myc) and hypertrophic markers (ANP, BNP, α-sk and β-MyHC), genes were determined by quantitative PCR (qPCR). The protein profiling of NPR-A, PKG-I and cGMP were evaluated by Western blot, immunofluorescence and ELISA respectively. A marked reduction in the level of expression of Npr1 (3- fold) and PKG-I (2.5-fold) genes and increased expression of proto-oncogenes (pANP mediated anti-hypertrophic activity was enhanced with either VA (pANP can be a novel therapeutical approach for the treatment and management of left ventricular cardiac hypertrophy. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Recombinant acylation stimulating protein administration to C3-/- mice increases insulin resistance via adipocyte inflammatory mechanisms.

    Directory of Open Access Journals (Sweden)

    Mercedes Nancy Munkonda

    Full Text Available BACKGROUND: Complement 3 (C3, a key component of the innate immune system, is involved in early inflammatory responses. Acylation stimulating protein (ASP; aka C3adesArg, a C3 cleavage product, is produced in adipose tissue and stimulates lipid storage. We hypothesized that, depending on the diet, chronic ASP administration in C3(-/- mice would affect lipid metabolism and insulin sensitivity via an adaptive adipose tissue inflammatory response. METHODOLOGY/PRINCIPAL FINDINGS: C3(-/- mice on normal low fat diet (ND or high fat diet (HFD were chronically administered recombinant ASP (rASP for 25 days via an osmotic mini-pump. While there was no effect on food intake, there was a decrease in activity, with a relative increase in adipose tissue weight on ND, and a shift in adipocyte size distribution. While rASP administration to C3(-/- mice on a ND increased insulin sensitivity, on a HFD, rASP administration had the opposite effect. Specifically, rASP administration in C3(-/- HFD mice resulted in decreased gene expression of IRS1, GLUT4, SREBF1 and NFκB in muscle, and decreased C5L2 but increased JNK, CD36, CD11c, CCR2 and NFκB gene expression in adipose tissue as well as increased secretion of proinflammatory cytokines (Rantes, KC, MCP-1, IL-6 and G-CSF. In adipose tissue, although IRS1 and GLUT4 mRNA were unchanged, insulin response was reduced. CONCLUSION: The effects of chronic rASP administration are tissue and diet specific, rASP administration enhances the HFD induced inflammatory response leading to an insulin-resistant state. These results suggest that, in humans, the increased plasma ASP associated with obesity and cardiovascular disease could be an additional factor directly contributing to development of metabolic syndrome, insulin resistance and diabetes.

  1. Hydrocarbons emitted by waggle-dancing honey bees increase forager recruitment by stimulating dancing.

    Science.gov (United States)

    Gilley, David C

    2014-01-01

    Hydrocarbons emitted by waggle-dancing honey bees are known to reactivate experienced foragers to visit known food sources. This study investigates whether these hydrocarbons also increase waggle-dance recruitment by observing recruitment and dancing behavior when the dance compounds are introduced into the hive. If the hydrocarbons emitted by waggle-dancing bees affect the recruitment of foragers to a food source, then the number of recruits arriving at a food source should be greater after introduction of dance compounds versus a pure-solvent control. This prediction was supported by the results of experiments in which recruits were captured at a feeder following introduction of dance-compounds into a hive. This study also tested two nonexclusive behavioral mechanism(s) by which the compounds might stimulate recruitment; 1) increased recruitment could occur by means of increasing the recruitment effectiveness of each dance and/or 2) increased recruitment could occur by increasing the intensity of waggle-dancing. These hypotheses were tested by examining video records of the dancing and recruitment behavior of individually marked bees following dance-compound introduction. Comparisons of numbers of dance followers and numbers of recruits per dance and waggle run showed no significant differences between dance-compound and solvent-control introduction, thus providing no support for the first hypothesis. Comparison of the number of waggle-dance bouts and the number of waggle runs revealed significantly more dancing during morning dance-compound introduction than morning solvent-control introduction, supporting the second hypothesis. These results suggest that the waggle-dance hydrocarbons play an important role in honey bee foraging recruitment by stimulating foragers to perform waggle dances following periods of inactivity.

  2. Azithromycin increases in vitro fibronectin production through interactions between macrophages and fibroblasts stimulated with Pseudomonas aeruginosa

    Science.gov (United States)

    Cory, Theodore J.; Birket, Susan E.; Murphy, Brian S.; Mattingly, Cynthia; Breslow-Deckman, Jessica M.; Feola, David J.

    2013-01-01

    Objectives Chronic azithromycin therapy has been associated with improved clinical outcomes in patients with cystic fibrosis (CF) who are chronically infected with Pseudomonas aeruginosa. We have previously demonstrated that azithromycin polarizes macrophages towards an alternatively activated phenotype, thereby blunting inflammation associated with infection. Because this phenotype is pro-fibrotic, it is important to evaluate azithromycin's consequential effects upon fibroblast function and extracellular matrix (ECM) protein production. Methods We co-cultured macrophages and fibroblasts together and stimulated them by adding P. aeruginosa or lipopolysaccharide to assess the ability of azithromycin to alter the macrophage phenotype, along with the impact exerted upon the production of fibronectin and other effectors that govern tissue remodelling, including transforming growth factor β (TGFβ), matrix metalloproteinase-9 (MMP-9) and arginase. We supported these studies by evaluating the impact of azithromycin treatment on these proteins in a mouse model of P. aeruginosa infection. Results Azithromycin increased arginase expression in vitro, as well as the activation of latent TGFβ, consistent with polarization to the alternative macrophage phenotype. While the drug increased fibronectin concentrations after stimulation in vitro, secretion of the ECM-degrading enzyme MMP-9 was also increased. Neutralization of active TGFβ resulted in the ablation of azithromycin's ability to increase fibronectin concentrations, but did not alter its ability to increase MMP-9 expression. In P. aeruginosa-infected mice, azithromycin significantly decreased MMP-9 and fibronectin concentrations in the alveolar space compared with non-treated, infected controls. Conclusions Our results suggest that azithromycin's effect on MMP-9 is regulated independently of TGFβ activity. Additionally, the beneficial effects of azithromycin may be partially due to effects on homeostasis in which ECM

  3. Epalrestat increases glutathione, thioredoxin, and heme oxygenase-1 by stimulating Nrf2 pathway in endothelial cells

    Directory of Open Access Journals (Sweden)

    Kaori Yama

    2015-04-01

    Full Text Available Epalrestat (EPS is the only aldose reductase inhibitor that is currently available for the treatment of diabetic neuropathy. Recently, we found that EPS at near-plasma concentration increases the intracellular levels of glutathione (GSH in rat Schwann cells. GSH plays a crucial role in protecting endothelial cells from oxidative stress, thereby preventing vascular diseases. Here we show that EPS increases GSH levels in not only Schwann cells but also endothelial cells. Treatment of bovine aortic endothelial cells (BAECs, an in vitro model of the vascular endothelium, with EPS caused a dramatic increase in intracellular GSH levels. This was concomitant with the up-regulation of glutamate cysteine ligase, an enzyme catalyzing the first and rate-limiting step in de novo GSH synthesis. Moreover, EPS stimulated the expression of thioredoxin and heme oxygenase-1, which have important redox regulatory functions in endothelial cells. Nuclear factor erythroid 2-related factor 2 (Nrf2 is a key transcription factor that regulates the expression of antioxidant genes. EPS increased nuclear Nrf2 levels in BAECs. Nrf2 knockdown by siRNA suppressed the EPS-induced glutamate cysteine ligase, thioredoxin-1, and heme oxygenase-1 expression. Interestingly, LY294002, an inhibitor of phosphatidylinositol 3-kinase, abolished the EPS-stimulated GSH synthesis, suggesting that the kinase is associated with Nrf2 activation induced by EPS. Furthermore, EPS reduced the cytotoxicity induced by H2O2 and tert-butylhydroperoxide, indicating that EPS plays a role in protecting cells from oxidative stress. Taken together, the results provide evidence that EPS exerts new beneficial effects on endothelial cells by increasing GSH, thioredoxin, and heme oxygenase-1 levels through the activation of Nrf2. We suggest that EPS has the potential to prevent several vascular diseases caused by oxidative stress.

  4. Hydrocarbons emitted by waggle-dancing honey bees increase forager recruitment by stimulating dancing.

    Directory of Open Access Journals (Sweden)

    David C Gilley

    Full Text Available Hydrocarbons emitted by waggle-dancing honey bees are known to reactivate experienced foragers to visit known food sources. This study investigates whether these hydrocarbons also increase waggle-dance recruitment by observing recruitment and dancing behavior when the dance compounds are introduced into the hive. If the hydrocarbons emitted by waggle-dancing bees affect the recruitment of foragers to a food source, then the number of recruits arriving at a food source should be greater after introduction of dance compounds versus a pure-solvent control. This prediction was supported by the results of experiments in which recruits were captured at a feeder following introduction of dance-compounds into a hive. This study also tested two nonexclusive behavioral mechanism(s by which the compounds might stimulate recruitment; 1 increased recruitment could occur by means of increasing the recruitment effectiveness of each dance and/or 2 increased recruitment could occur by increasing the intensity of waggle-dancing. These hypotheses were tested by examining video records of the dancing and recruitment behavior of individually marked bees following dance-compound introduction. Comparisons of numbers of dance followers and numbers of recruits per dance and waggle run showed no significant differences between dance-compound and solvent-control introduction, thus providing no support for the first hypothesis. Comparison of the number of waggle-dance bouts and the number of waggle runs revealed significantly more dancing during morning dance-compound introduction than morning solvent-control introduction, supporting the second hypothesis. These results suggest that the waggle-dance hydrocarbons play an important role in honey bee foraging recruitment by stimulating foragers to perform waggle dances following periods of inactivity.

  5. Annexin A7 deficiency potentiates cardiac NFAT activity promoting hypertrophic signaling

    Energy Technology Data Exchange (ETDEWEB)

    Voelkl, Jakob; Alesutan, Ioana; Pakladok, Tatsiana; Viereck, Robert; Feger, Martina; Mia, Sobuj [Department of Physiology, University of Tübingen, Tübingen (Germany); Schönberger, Tanja [Department of Cardiology and Cardiovascular Medicine, University of Tübingen, Tübingen (Germany); Noegel, Angelika A. [Center for Biochemistry, Institute of Biochemistry I, University of Cologne, Köln (Germany); Gawaz, Meinrad [Department of Cardiology and Cardiovascular Medicine, University of Tübingen, Tübingen (Germany); Lang, Florian, E-mail: florian.lang@uni-tuebingen.de [Department of Physiology, University of Tübingen, Tübingen (Germany)

    2014-02-28

    Highlights: • Cardiac Anxa7 expression was up-regulated following TAC. • The hypertrophic response following TAC was augmented in Anxa7-deficient mice. • Silencing of Anxa7 increased indicators of HL-1 cardiomyocytes hypertrophy. • Silencing of Anxa7 induced Nfatc1 nuclear translocation. • Silencing of Anxa7 enhanced NFAT-dependent transcriptional activity. - Abstract: Annexin A7 (Anxa7) is a cytoskeletal protein interacting with Ca{sup 2+} signaling which in turn is a crucial factor for cardiac remodeling following cardiac injury. The present study explored whether Anxa7 participates in the regulation of cardiac stress signaling. To this end, mice lacking functional Anxa7 (anxa7{sup −/−}) and wild-type mice (anxa7{sup +/+}) were investigated following pressure overload by transverse aortic constriction (TAC). In addition, HL-1 cardiomyocytes were silenced with Anxa7 siRNA and treated with isoproterenol. Transcript levels were determined by quantitative RT-PCR, transcriptional activity by luciferase reporter assay and protein abundance by Western blotting and confocal microscopy. As a result, TAC treatment increased the mRNA and protein levels of Anxa7 in wild-type mice. Moreover, TAC increased heart weight to body weight ratio and the cardiac mRNA levels of αSka, Nppb, Col1a1, Col3a1 and Rcan1, effects more pronounced in anxa7{sup −/−} mice than in anxa7{sup +/+} mice. Silencing of Anxa7 in HL-1 cardiomyocytes significantly increased nuclear localization of Nfatc1. Furthermore, Anxa7 silencing increased NFAT-dependent transcriptional activity as well as αSka, Nppb, and Rcan1 mRNA levels both, under control conditions and following β-adrenergic stimulation by isoproterenol. These observations point to an important role of annexin A7 in the regulation of cardiac NFAT activity and hypertrophic response following cardiac stress conditions.

  6. Dissociation between phytohaemagglutinin-stimulated generation of inositol phosphates and Ca2+ increase in human mononuclear leucocytes

    NARCIS (Netherlands)

    Michel, M. C.; van Tits, L. J.; Trenn, G.; Sykora, J.; Brodde, O. E.

    1992-01-01

    We have tested whether phytohaemagglutinin (PHA)-stimulated generation of inositol phosphates (IP) and increases in intracellular Ca2+ can be dissociated in human mononuclear leucocytes. Lowering the incubation temperature from 37 degrees to 25 degrees C decreased PHA-stimulated IP generation by

  7. Large increase of the use of psycho-stimulants among youth in the Netherlands between 1996 and 2006

    NARCIS (Netherlands)

    Trip, Anne-Marie; Visser, Sipke T.; Kalverdijk, Luuk J.; de Jong-van den Berg, Lolkje T. W.

    WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT? center dot In the USA psycho-stimulant use has increased rapidly in the 1990s and stabilized around 2000. center dot This study describes the prevalence of psycho-stimulant use between1996 and 2006 in the Netherlands. WHAT THIS STUDY ADDS center dot The

  8. Hypertrophic Obesity and Subcutaneous Adipose Tissue Dysfunction

    Directory of Open Access Journals (Sweden)

    Anna Meiliana

    2014-08-01

    Full Text Available BACKGROUND: Over the past 50 years, scientists have recognized that not all adipose tissue is alike, and that health risk is associated with the location as well as the amount of body fat. Different depots are sufficiently distinct with respect to fatty-acid storage and release as to probably play unique roles in human physiology. Whether fat redistribution causes metabolic disease or whether it is a marker of underlying processes that are primarily responsible is an open question. CONTENT: The limited expandability of the subcutaneous adipose tissue leads to inappropriate adipose cell expansion (hypertrophic obesity with local inflammation and a dysregulated and insulin-resistant adipose tissue. The inability to store excess fat in the subcutaneous adipose tissue is a likely key mechanism for promoting ectopic fat accumulation in tissues and areas where fat can be stored, including the intra-abdominal and visceral areas, in the liver, epi/pericardial area, around vessels, in the myocardium, and in the skeletal muscles. Many studies have implicated ectopic fat accumulation and the associated lipotoxicity as the major determinant of the metabolic complications of obesity driving systemic insulin resistance, inflammation, hepatic glucose production, and dyslipidemia. SUMMARY: In summary, hypertrophic obesity is due to an impaired ability to recruit and differentiate available adipose precursor cells in the subcutaneous adipose tissue. Thus, the subcutaneous adipose tissue may be particular in its limited ability in certain individuals to undergo adipogenesis during weight increase. Inability to promote subcutaneous adipogenesis under periods of affluence would favor lipid overlow and ectopic fat accumulation with negative metabolic consequences. KEYWORDS: obesity, adipogenesis, subcutaneous adipose tissue, visceral adipose tissue, adipocyte dysfunction.

  9. Increasing Sucrose Uptake Capacity of Wheat Grains Stimulates Storage Protein Synthesis1[W

    Science.gov (United States)

    Weichert, Nicola; Saalbach, Isolde; Weichert, Heiko; Kohl, Stefan; Erban, Alexander; Kopka, Joachim; Hause, Bettina; Varshney, Alok; Sreenivasulu, Nese; Strickert, Marc; Kumlehn, Jochen; Weschke, Winfriede; Weber, Hans

    2010-01-01

    Increasing grain sink strength by improving assimilate uptake capacity could be a promising approach toward getting higher yield. The barley (Hordeum vulgare) sucrose transporter HvSUT1 (SUT) was expressed under control of the endosperm-specific Hordein B1 promoter (HO). Compared with the wild type, transgenic HOSUT grains take up more sucrose (Suc) in vitro, showing that the transgene is functional. Grain Suc levels are not altered, indicating that Suc fluxes are influenced rather than steady-state levels. HOSUT grains have increased percentages of total nitrogen and prolamins, which is reflected in increased levels of phenylalanine, tyrosine, tryptophan, isoleucine, and leucine at late grain development. Transcript profiling indicates specific stimulation of prolamin gene expression at the onset of storage phase. Changes in gene expression and metabolite levels related to carbon metabolism and amino acid biosynthesis suggest deregulated carbon-nitrogen balance, which together indicate carbon sufficiency and relative depletion of nitrogen. Genes, deregulated together with prolamin genes, might represent candidates, which respond positively to assimilate supply and are related to sugar-starch metabolism, cytokinin and brassinosteroid functions, cell proliferation, and sugar/abscisic acid signaling. Genes showing inverse expression patterns represent potential negative regulators. It is concluded that HvSUT1 overexpression increases grain protein content but also deregulates the metabolic status of wheat (Triticum aestivum) grains, accompanied by up-regulated gene expression of positive and negative regulators related to sugar signaling and assimilate supply. In HOSUT grains, alternating stimulation of positive and negative regulators causes oscillatory patterns of gene expression and highlights the capacity and great flexibility to adjust wheat grain storage metabolism in response to metabolic alterations. PMID:20018590

  10. The Comparision of Left Atrial Functions Between Hypertrophic Cardiomyopathy and Hypertension

    Directory of Open Access Journals (Sweden)

    Ahmet Akdi

    2016-12-01

    Full Text Available INTRODUCTION: The presence of left ventricule hypertrophy (LVH due to arterial hypertension may impair atrial function. Also, hypertrophic cardiomyopathy (HCM represents a generalized myopathic process affecting both ventricular and atrial myocardium. In this study we aimed to evaluate left atrial volumes, phasic functions in hypertrophic cardiomyopathy and hypertensive heart disease. METHODS: The study consisted of 42 patients (25 men, 17 women; mean age 51.2 years with hypertrophic cardiomyopathy (n = 20 or hypertensive heart disease (n = 22. Two-dimensional echocardiographic left atrial volumes (maximal, minimal and pre-contraction volumes were obtained and left atrial phasic functions (reservoir, conduit, and pumping functions were calculated. The findings were compared with those of age- and sex-matched 20 controls (9 men, 11 women; mean age 44.2 years without structural heart disease. RESULTS: Left atrial volumes were found to be significantly increased in patients with hypertrophic cardiomyopathy and hypertensive heart disease compared with control groups. Left atrial reservoir and conduit functions were significantly lower in patients with hypertrophic cardiomyopathy than in those with hypertensive heart disease and control groups (p < 0.01 and p < 0.01, respectively. There was no significant difference of left atrial pumping functions between study groups (p = 0.2. DISCUSSION AND CONCLUSION: This study showed that left atrial minimal, maximal and pre-contraction volume indexes are increased in hypertensive and hypertrophic cardiomyopathy groups compared with control group, but there was no significant difference between hypertrophic cardiomyopathy and hypertensive patients. In hypertrophic cardiomyopathy group left atrial phasic functions, including conduit, reservoir and pump, were decreased significantly more than hypertensive and control group. In hypertensive patients left atrial phasic functions were decreased but compared with

  11. In vivo charge injection limits increased after 'unsafe' stimulation

    DEFF Research Database (Denmark)

    Meijs, Suzan; Sørensen, Søren; Rechendorff, Kristian

    2015-01-01

    was not observed with any of the stimulation protocols and no tissue damage was observed for the 20 mA – 200 Hz stimulation group. This indicates that the ‘safe potential window’ may not be applicable in vivo, as no damage was done stimulating with 20 mA at 200 Hz, while damage was done using the same current...

  12. Focal increase of blood flow in the cerebral cortex of man during vestibular stimulation

    DEFF Research Database (Denmark)

    Friberg, L; Olsen, T S; Roland, P E

    1985-01-01

    meatus was irrigated with water at body temperature as a control to vestibular stimulation. During vestibular stimulation there was only a single cortical area, located in the superior temporal region, which showed a consistent focal activation in the hemisphere contralateral to the stimulated side...

  13. Stimulation of marketing channels of innovations participants as the way of increasing its management efficiency

    OpenAIRE

    L.О. Syhyda

    2012-01-01

    In article participants of distribution marketing channel are defined. Variants of manufacturer stimulation carrying out are separated. Stages of stimulation process in marketing channel are offered. Methods of stimulation carrying out in marketing channels of traditional and innovative production are defined.

  14. Stimulation of osteoblasts with Emdogain increases the expression of specific mineralization markers.

    Science.gov (United States)

    Weishaupt, Peggy; Bernimoulin, Jean-Pierre; Trackman, Philip; Hägewald, Stefan

    2008-08-01

    The purpose of this study was to determine the effects of enamel matrix derivative on mRNA expression of markers related to periodontal healing. Murine osteoprogenitor cells (MC3T3-E1) were grown for 12 and 16 days in mineralization media and stimulated with 100 microg/mL Emdogain (EMD). Cell cultures treated with 2% and 10% fetal calf serum (FCS) served as control. The mRNA expression of bone sialoprotein (BSP), osteopontin (OPN), and runt-related protein 2 (Runx2) was analyzed by real-time polymerase chain reaction. One-way analysis of variance was used for statistical analysis. Stimulation with EMD significantly (P < .01) enhanced mRNA expression of BSP up to 13.9-fold and of OPN up to 3.2-fold at day 16 compared with the 2% FCS control. The expression of mRNA for transcription factor Runx2 was not significantly changed. The beneficial effects seen in periodontal regeneration after treatment with EMD may be related to an increase of the mineralization markers BSP and OPN at mRNA level.

  15. Gastrin stimulates renal dopamine production by increasing the renal tubular uptake of l-DOPA.

    Science.gov (United States)

    Jiang, Xiaoliang; Zhang, Yanrong; Yang, Yu; Yang, Jian; Asico, Laureano D; Chen, Wei; Felder, Robin A; Armando, Ines; Jose, Pedro A; Yang, Zhiwei

    2017-01-01

    Gastrin is a peptide hormone that is involved in the regulation of sodium balance and blood pressure. Dopamine, which is also involved in the regulation of sodium balance and blood pressure, directly or indirectly interacts with other blood pressure-regulating hormones, including gastrin. This study aimed to determine the mechanisms of the interaction between gastrin and dopamine and tested the hypothesis that gastrin produced in the kidney increases renal dopamine production to keep blood pressure within the normal range. We show that in human and mouse renal proximal tubule cells (hRPTCs and mRPTCs, respectively), gastrin stimulates renal dopamine production by increasing the cellular uptake of l-DOPA via the l-type amino acid transporter (LAT) at the plasma membrane. The uptake of l-DOPA in RPTCs from C57Bl/6J mice is lower than in RPTCs from normotensive humans. l-DOPA uptake in renal cortical slices is also lower in salt-sensitive C57Bl/6J than in salt-resistant BALB/c mice. The deficient renal cortical uptake of l-DOPA in C57Bl/6J mice may be due to decreased LAT-1 activity that is related to its decreased expression at the plasma membrane, relative to BALB/c mice. We also show that renal-selective silencing of Gast by the renal subcapsular injection of Gast siRNA in BALB/c mice decreases renal dopamine production and increases blood pressure. These results highlight the importance of renal gastrin in stimulating renal dopamine production, which may give a new perspective in the prevention and treatment of hypertension. Copyright © 2017 the American Physiological Society.

  16. Stimulating in situ surfactant production to increase contaminant bioavailability and augment bioremediation of petroleum hydrocarbons

    Science.gov (United States)

    Haws, N. W.; Bentley, H. W.; Yiannakakis, A.; Bentley, A. J.; Cassidy, D. P.

    2006-12-01

    The effectiveness of a bioremediation strategy is largely dependent on relationships between contaminant sequestration (geochemical limitations) and microbial degradation potential (biological limitations). As contaminant bioavailability becomes mass transfer limited, contaminant removal will show less sensitivity to biodegradation enhancements without concurrent enhancements to rates of mass transfer into the bioavailable phase. Implementing a strategy that can simultaneously address geochemical and biological limitations is motivated by a subsurface zone of liquid petroleum hydrocarbons (LPH) contamination that is in excess of 10 acres (40,000 sq. meters). Biodegradation potential at the site is high; however, observed biodegradation rates are generally low, indicative of bioavailability limitations (e.g., low aqueous solubilities, nutrient deficiencies, and/or mass transfer limitations), and estimates indicate that bioremediation (i.e., biosparging/bioventing) with unaugmented biodegradation may be unable to achieve the remedial objectives within an acceptable time. Bench-scale experiments using soils native to the site provide evidence that, in addition to nutrient additions, a pulsed oxygen delivery can increase biodegradation rates by stimulating the microbial production of biosurfactants (rhamnolipids), leading to a reduction in surface tension and an increase in contaminant bioavailability. Pilot-scale tests at the field site are evaluating the effectiveness of stimulating in situ biosurfactant production using cyclic biosparging. The cyclic sparging creates extended periods of alternating aerobic and oxygen-depleted conditions in the submerged smear zone. The increased bioavailability of LPH and the resulting biodegradation enhancements during the test are evaluated using measurements of surface tension (as confirmation of biosurfactant accumulation) and nitrate concentrations (as substantiation of anaerobic biodegradation during shut-off periods). The

  17. Hypertrophic Nonunion Humerus Mimicking an Enchondroma

    Directory of Open Access Journals (Sweden)

    N. K. Magu

    2014-01-01

    Full Text Available Introduction. Although fractures of humeral shaft show excellent results with conservative management, nonunion does occur. Case Report. We bring forth the case of a young male with a 1.5-year-old hypertrophic nonunion of the humerus mimicking an enchondroma. The initial X-ray images of the patient appeared to be an enchondroma, which only on further evaluation and histopathological analysis was diagnosed conclusively to be a hypertrophic nonunion. Discussion. Enchondromas are often incidentally diagnosed benign tumours. It is however not common to misdiagnose a hypertrophic nonunion to be an enchondroma. We present this case to highlight the unique diagnostic dilemma the treating team had to face.

  18. Hypertrophic lupus vulgaris: an unusual presentation.

    Science.gov (United States)

    Jain, Vijay K; Aggarwal, Kamal; Jain, Sarika; Singh, Sunita

    2009-07-01

    Lupus vulgaris is the most common form of cutaneous tuberculosis occurring in previously sensitized individuals with a high degree of tuberculin sensitivity. Various forms including plaque, ulcerative, hypertrophic, vegetative, papular, and nodular forms have been described. A 30-year-old male patient presented with a very large hypertrophic lupus vulgaris lesion over left side of chest since 22 years. Histopathological examination showed granulomatous infiltration without caseation necrosis. The Mantoux reaction was strongly positive. Hypertrophic lupus vulgaris of such a giant size and that too at an unusual site is extremely rare and hence is being reported.

  19. Stimulation of the ventral tegmental area increased nociceptive thresholds and decreased spinal dorsal horn neuronal activity in rat.

    Science.gov (United States)

    Li, Ai-Ling; Sibi, Jiny E; Yang, Xiaofei; Chiao, Jung-Chih; Peng, Yuan Bo

    2016-06-01

    Deep brain stimulation has been found to be effective in relieving intractable pain. The ventral tegmental area (VTA) plays a role not only in the reward process, but also in the modulation of nociception. Lesions of VTA result in increased pain thresholds and exacerbate pain in several pain models. It is hypothesized that direct activation of VTA will reduce pain experience. In this study, we investigated the effect of direct electrical stimulation of the VTA on mechanical, thermal and carrageenan-induced chemical nociceptive thresholds in Sprague-Dawley rats using our custom-designed wireless stimulator. We found that: (1) VTA stimulation itself did not show any change in mechanical or thermal threshold; and (2) the decreased mechanical and thermal thresholds induced by carrageenan injection in the hind paw contralateral to the stimulation site were significantly reversed by VTA stimulation. To further explore the underlying mechanism of VTA stimulation-induced analgesia, spinal cord dorsal horn neuronal responses to graded mechanical stimuli were recorded. VTA stimulation significantly inhibited dorsal horn neuronal activity in response to pressure and pinch from the paw, but not brush. This indicated that VTA stimulation may have exerted its analgesic effect via descending modulatory pain pathways, possibly through its connections with brain stem structures and cerebral cortex areas.

  20. Muscle stimulation waveform timing patterns for upper and lower leg muscle groups to increase muscular endurance in functional electrical stimulation pedaling using a forward dynamic model.

    Science.gov (United States)

    Hakansson, Nils A; Hull, M L

    2009-09-01

    Functional electrical stimulation (FES) of pedaling provides a means by which individuals with spinal cord injury can obtain cardiorespiratory exercise. However, the early onset of muscle fatigue is a limiting factor in the cardiorespiratory exercise obtained while pedaling an FES ergometer. One objective of this study was to determine muscle excitation timing patterns to increase muscle endurance in FES pedaling for three upper leg muscle groups and to compare these timing patterns to those used in a commercially available FES ergometer. The second objective was to determine excitation timing patterns for a lower leg muscle group in conjunction with the three upper leg muscle groups. The final objective was to determine the mechanical energy contributions of each of the muscle groups to drive the crank. To fulfill these objectives, we developed a forward dynamic simulation of FES pedaling to determine electrical stimulation on and off times that minimize the muscle stress-time integral of the stimulated muscles. The computed electrical stimulation on and off times differed from those utilized by a commercially available FES ergometer and resulted in 17% and 11% decrease in the muscle stress-time integral for the three upper leg muscle groups and four upper and lower leg muscle groups, respectively. Also, the duration of muscle activation by the hamstrings increased by 5% over a crank cycle for the computed stimulation on and off times, and the mechanical energy generated by the hamstrings increased by 20%. The lower leg muscle group did not generate sufficient mechanical energy to reduce the energy contributions of the upper leg muscle groups. The computed stimulation on and off times could prolong FES pedaling, and thereby provide improved cardiorespiratory and muscle training outcomes for individuals with spinal cord injury. Including the lower leg muscle group in FES pedaling could increase cardiorespiratory demand while not affecting the endurance of the

  1. Does navigated transcranial stimulation increase the accuracy of tractography? A prospective clinical trial based on intraoperative motor evoked potential monitoring during deep brain stimulation.

    Science.gov (United States)

    Forster, Marie-Therese; Hoecker, Alexander Claudius; Kang, Jun-Suk; Quick, Johanna; Seifert, Volker; Hattingen, Elke; Hilker, Rüdiger; Weise, Lutz Martin

    2015-06-01

    Tractography based on diffusion tensor imaging has become a popular tool for delineating white matter tracts for neurosurgical procedures. To explore whether navigated transcranial magnetic stimulation (nTMS) might increase the accuracy of fiber tracking. Tractography was performed according to both anatomic delineation of the motor cortex (n = 14) and nTMS results (n = 9). After implantation of the definitive electrode, stimulation via the electrode was performed, defining a stimulation threshold for eliciting motor evoked potentials recorded during deep brain stimulation surgery. Others have shown that of arm and leg muscles. This threshold was correlated with the shortest distance between the active electrode contact and both fiber tracks. Results were evaluated by correlation to motor evoked potential monitoring during deep brain stimulation, a surgical procedure causing hardly any brain shift. Distances to fiber tracks clearly correlated with motor evoked potential thresholds. Tracks based on nTMS had a higher predictive value than tracks based on anatomic motor cortex definition (P < .001 and P = .005, respectively). However, target site, hemisphere, and active electrode contact did not influence this correlation. The implementation of tractography based on nTMS increases the accuracy of fiber tracking. Moreover, this combination of methods has the potential to become a supplemental tool for guiding electrode implantation.

  2. Optokinetic stimulation increases limb pain and forehead hyperalgesia in complex regional pain syndrome

    DEFF Research Database (Denmark)

    Knudsen, Lone F.; Drummond, Peter D.

    2015-01-01

    BACKGROUND: Ambiguous visual stimuli increase limb pain in patients with complex regional pain syndrome (CRPS), possibly due to afferent sensory feedback conflicts. Conflicting sensory stimuli can also generate unpleasant sensations in healthy people such as during motion sickness. We wanted...... to investigate the mechanisms underlying the link between sensory conflicts and pain in CRPS using optokinetic stimulation (OKS) - a method known to induce motion sickness. METHODS: Twenty-one CRPS patients underwent OKS and rated symptoms of motion sickness. Patients also rated limb pain and pain....... In a subgroup of nauseated patients who withdrew early from OKS, hyperalgesia to pressure in the ipsilateral forehead persisted longer than in the remaining participants. Sharpness sensations remained constant at all sites. CONCLUSIONS: Sensory conflicts may facilitate pain in CRPS by activating the mechanisms...

  3. VEGF increases the permeability of sheep pleura ex vivo through VEGFR2 stimulation.

    Science.gov (United States)

    Peppa, Vasiliki I; Arsenopoulou, Zoi V; Zarogiannis, Sotirios G; Deligiorgi, Triantafyllia; Jagirdar, Rajesh; Makantasis, Ioannis; Stefanidis, Ioannis; Liakopoulos, Vassilios; Molyvdas, Paschalis-Adam; Gourgoulianis, Konstantinos I; Hatzoglou, Chrissi

    2014-10-01

    Vascular endothelial growth factor (VEGF), a cytokine that increases vascular permeability to water and proteins and induces angiogenesis, has been implicated in the development of pleural effusions. Inflammatory and malignant pleural effusions are rich in VEGF content while mesothelial cells produce and excrete VEGF. In this report we aimed at investigating by means of electrophysiology the direct effects of VEGF on the parietal and visceral sheep pleura as well as the type of receptors that mediate this effect. Our findings show that VEGF has a direct effect on the pleural mesothelium rendering it more permeable and this effect is mediated through the stimulation of VEGF receptor 2. Our findings shed more light to the role of VEGF in the pathogenesis of pleural effusions and provide functional evidence for a role of VEGFR2 on the pleural mesothelium that has never been studied before. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Stimulation of body weight increase and epiphyseal cartilage growth by insulin like growth factor

    Science.gov (United States)

    Ellis, S.

    1981-01-01

    The ability of insulin-like growth factor (IGF) to induce growth in hypophysectomized immature rats was tested by continuous infusion of the partially purified factor at daily doses of 6, 21, and 46 mU for an 8-day period. A dose-dependent growth of the proximal epiphyseal cartilage of the tibia and an associated stimulation of the primary spongiosa were produced by these amounts of IGF. The two highest doses of IGF also resulted in dose-dependent increases of body weight. Gel permeation of the sera at neutrality showed that the large-molecular-weight IGF binding protein was not induced by the infusion of IGF, whereas it ws generated in the sera of hypophysectomized rats that were infused with daily doses of 86 mU of human growth hormone.

  5. Cell-surface glycosyltransferases in cultured fibroblasts: increased activity and release during serum stimulation of growth.

    Science.gov (United States)

    LaMont, J T; Gammon, M T; Isselbacher, K J

    1977-01-01

    Cell-surface galactosyltransferase was studied in suspensions of intact baby hamster kidney fibroblasts with both endogenous and exogenous glycoprotein acceptors. The cell-surface location of galactosyltransferase was demonstrated in experiments with the enzyme modifier alpha-lactalbumin, which does not enter the cell. The addition of alpha-lactalbumin to the assay medium for galactosyltransferase resulted in accumulation of lactose in the medium but not in the cells. There was no detectable hydrolysis of UDP-galactose to free galactose by these cells, nor did a 100-fold molar excess of free galactose inhibit cell-surface galactosyltransferase. There was a marked increase in specific activity of cell-surface exogenous galactosyltransferase in serum-stimulated as compared to resting fibroblasts. Dividing but not resting fibroblasts released galactosyltransferase, but not sialyl- or fucosyltransferase, in soluble form into the tissue culture medium. The release of galactosyltransferase was greater from virally transformed than from nontransformed fibroblasts. PMID:191828

  6. Pro-Inflammatory Cytokine Surge After Injury Stimulates An Airway Immunoglobulin A Increase

    Science.gov (United States)

    Jonker, Mark A; Sano, Yoshifumi; Hermsen, Joshua L; Lan, Jinggang; Kudsk, Kenneth A

    2010-01-01

    Background Injury stimulates an innate airway IgA response in severely injured patients, which also occurs in mice. Tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) stimulate the production of polymeric immunoglobulin receptor (pIgR), the protein required to transport immunoglobulin A (IgA) to mucosal surfaces. Blockade of TNF-α and IL-1β eliminates the airway IgA response to injury. IL-6 stimulates differentiation of B cells into IgA secreting plasma cells at mucosal sites. We investigated the local and systemic kinetics of TNF-α, IL-1β, and IL-6 after injury in mice. We also hypothesized that injection of exogenous TNF-α, IL-1β, and IL-6 would replicate the airway IgA response to injury. Methods Experiment 1: Male Institute of Cancer Research (ICR) mice were randomized to uninjured controls (n = 8) or to surgical stress with laparotomy and neck incisions with sacrifice at 1, 2, 3, 5, or 8 hours after injury (n = 8/group). Bronchoalveolar lavage (BAL) and serum levels of TNF-α, IL-1β, and IL-6 were analyzed by ELISA. Experiment 2: Male ICR mice were randomized to uninjured controls (n = 6), Injury (surgical stress that was similar to expt 1 except the peritoneum was left intact, n = 6), or Cytokine injection with intraperitoneal injection of recombinant TNF-α, IL-1β, and IL-6. Animals were sacrificed at 2 hours after injury and nasal airway lavage and bronchoalveolar lavage IgA were analyzed by ELISA. Results Experiment 1: BAL TNF-α, IL-1β and IL-6 levels increased in bimodal pattern after injury at 3 h and 8 h vs controls (p<0.05). Serum IL-6 did not increase at 3 h, but did show a significant increase by 5 h vs control (p<0.05). Serum levels of TNF-α and IL-1β did not change. Experiment 2: Both Injury and combination TNF-α, IL-1β and IL-6 cytokine injection significantly increased IgA levels in airway lavage (BAL+NAL) compared to control (p<0.01 for both). Conclusions Airway levels of TNF-α, IL-1β, and IL-6 increase in a

  7. Myocardial ischemia in hypertrophic cardiomyopathy; Isquemia miocardica na cardiomiopatia hipertrofica

    Energy Technology Data Exchange (ETDEWEB)

    Lima Filho, Moyses de Oliveira; Figueiredo, Geraldo L.; Simoes, Marcus V.; Pyntia, Antonio O.; Marin Neto, Jose Antonio [Sao Paulo Univ., Ribeirao Preto, SP (Brazil). Faculdade de Medicina. Div. de Cardiologia

    2000-08-01

    Myocardial ischemia in hypertrophic cardiomyopathy is multifactorial and explains the occurrence of angina, in about 50% of patients. The pathophysiology of myocardial ischemia may be explained by the increase of the ventricular mass and relative paucity of the coronary microcirculation; the elevated ventricular filling pressures and myocardial stiffness causing a compression of the coronary microvessels; the impaired coronary vasodilator flow reserve caused by anatomic and functional abnormalities; and the systolic compression of epicardial vessel (myocardial bridges). Myocardial ischemia must be investigated by perfusion scintigraphic methods since its presence influences the prognosis and has relevant clinical implications for management of patients. Patients with hypertrophic cardiomyopathy and documented myocardial ischemia usually need to undergo invasive coronary angiography to exclude the presence of concomitant atherosclerotic coronary disease. (author)

  8. Hypertrophic cardiomyopathy screening in young athletes

    Energy Technology Data Exchange (ETDEWEB)

    Rappoport, W.J. [Arizona Heart Inst., Phoenix, AZ (United States); Steingard, P.M. [Phoenix Suns, Phoenix, AZ (United States)

    2006-07-01

    Hypertrophic cardiomyopathy is the leading cause of sudden death during vigorous exercise. Early identification of this abnormality by ECG screening of high-school athletes before they participate in competitive sports helps save lives. (orig.)

  9. Verrucous (Hypertrophic) Cutaneous Lupus Erythematosus: A Case ...

    African Journals Online (AJOL)

    Abstract. Verrucous (Hypertrophic) Lupus Erythematosus (LE) represents a rare but distinct, variant of chronic discoid lupus erythematosus. We report a case of LE with verrucous lesions for its rarity and peculiar location posing a diagnostic dilemma.

  10. Transcranial random noise stimulation mitigates increased difficulty in an arithmetic learning task.

    Science.gov (United States)

    Popescu, Tudor; Krause, Beatrix; Terhune, Devin B; Twose, Olivia; Page, Thomas; Humphreys, Glyn; Cohen Kadosh, Roi

    2016-01-29

    Proficiency in arithmetic learning can be achieved by using a multitude of strategies, the most salient of which are procedural learning (applying a certain set of computations) and rote learning (direct retrieval from long-term memory). Here we investigated the effect of transcranial random noise stimulation (tRNS), a non-invasive brain stimulation method previously shown to enhance cognitive training, on both types of learning in a 5-day sham-controlled training study, under two conditions of task difficulty, defined in terms of item repetition. On the basis of previous research implicating the prefrontal and posterior parietal cortex in early and late stages of arithmetic learning, respectively, sham-controlled tRNS was applied to bilateral prefrontal cortex for the first 3 days and to the posterior parietal cortex for the last 2 days of a 5-day training phase. The training involved learning to solve arithmetic problems by applying a calculation algorithm; both trained and untrained problems were used in a brief testing phase at the end of the training phase. Task difficulty was manipulated between subjects by using either a large ("easy" condition) or a small ("difficult" condition) number of repetition of problems during training. Measures of attention and working memory were acquired before and after the training phase. As compared to sham, participants in the tRNS condition displayed faster reaction times and increased learning rate during the training phase; as well as faster reaction times for both trained and untrained (new) problems, which indicated a transfer effect after the end of training. All stimulation effects reached significance only in the "difficult" condition when number of repetition was lower. There were no transfer effects of tRNS on attention or working memory. The results support the view that tRNS can produce specific facilitative effects on numerical cognition--specifically, on arithmetic learning. They also highlight the importance of

  11. Conditional stimulation of the dorsal penile/clitoral nerve may increase cystometric capacity in patients with spinal cord injury.

    Science.gov (United States)

    Dalmose, A L; Rijkhoff, N J M; Kirkeby, H J; Nohr, M; Sinkjaer, T; Djurhuus, J C

    2003-01-01

    To investigate the feasibility of conditional short duration electrical stimulation of the penile/clitoral nerve as treatment for detrusor hyperreflexia, the present study was initiated. Ten patients with spinal cord injury, 4 women and 6 men, with lesions at different levels above the sacral micturition center had a standard cystometry performed. During a subsequent cystometry, conditional short duration electrical stimulation of the penile/clitoral nerve was performed as treatment for one or more detrusor hyperreflexic contractions. In all patients, at least one contraction (mean, 7.8; range, 1-16 contractions) was inhibited by the stimulations. The mean cystometric capacity was increased significantly by conditional electrical stimulation, from 210 mL in the control cystometries to 349 mL in the stimulation cystometries (P=0.016). The maximal detrusor pressure during the first contraction in the control cystometries was mean 51 cm H(2)O, whereas the maximal pressure of the first contraction in the stimulation cystometries was reduced to mean 33 cm H(2)O (P=0.045). The authors conclude that repeated conditional short duration electrical stimulation significantly increased cystometric capacity in patients with spinal cord injury. The increase was caused mainly by an inhibition of detrusor contractions. The need for a reliable technique for chronic bladder activity monitoring is emphasized, as it is a prerequisite for clinical application of this treatment modality. Copyright 2003 Wiley-Liss, Inc.

  12. Does microcurrent stimulation increase the range of movement of ankle dorsiflexion in children with cerebral palsy?

    Science.gov (United States)

    Mäenpää, Helena; Jaakkola, Riitta; Sandström, Marita; Von Wendt, Lennart

    2004-06-03

    To determine whether microcurrent stimulation (MENS) increases the range of motion (ROM) of the ankle joint in children with cerebral palsy. Twelve children with spastic hemiplegia (age range 4.5 to 16 years) with moderate myocontracture of the triceps surae, received MENS for 1 h five times a week for 4 weeks. An equally long baseline period was preceded. The assessments were: active and passive ROM of ankle dorsiflexion, popliteal flexion and ankle dorsiflexion in maximal flexion of knees in standing position while maintaining the heels in contact with the floor, one foot standing and hopping on one foot. After the treatment with MENS, the passive ROM of ankle dorsiflexion with both knees flexed and extended (p<0.001) increased significantly. Increases were also observed in popliteal flexion (p<0.001) and ankle dorsiflexion (p=0.0012) during maximal flexion of the knees in a standing position. The ROM of active dorsiflexion with the knee flexed (p<0.05) and one foot standing (p<0.05) also improved. Children and parents found this treatment easy to carry out. MENS relieves myocontracture and can enhance conventional rehabilitation programmes for children with cerebral palsy.

  13. Transcranial direct current stimulation over the left prefrontal cortex increases randomness of choice in instrumental learning.

    Science.gov (United States)

    Turi, Zsolt; Mittner, Matthias; Opitz, Alexander; Popkes, Miriam; Paulus, Walter; Antal, Andrea

    2015-02-01

    There is growing evidence from neuro-computational studies that instrumental learning involves the dynamic interaction of a computationally rigid, low-level striatal and a more flexible, high-level prefrontal component. To evaluate the role of the prefrontal cortex in instrumental learning, we applied anodal transcranial direct current stimulation (tDCS) optimized for the left dorsolateral prefrontal cortex, by using realistic MR-derived finite element model-based electric field simulations. In a study with a double-blind, sham-controlled, repeated-measures design, sixteen male participants performed a probabilistic learning task while receiving anodal and sham tDCS in a counterbalanced order. Compared to sham tDCS, anodal tDCS significantly increased the amount of maladaptive shifting behavior after optimal outcomes during learning when reward probabilities were highly dissociable. Derived parameters of the Q-learning computational model further revealed a significantly increased model parameter that was sensitive to random action selection in the anodal compared to the sham tDCS session, whereas the learning rate parameter was not influenced significantly by tDCS. These results congruently indicate that prefrontal tDCS during instrumental learning increased randomness of choice, possibly reflecting the influence of the cognitive prefrontal component. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Carbon-degrading enzyme activities stimulated by increased nutrient availability in Arctic tundra soils.

    Directory of Open Access Journals (Sweden)

    Akihiro Koyama

    Full Text Available Climate-induced warming of the Arctic tundra is expected to increase nutrient availability to soil microbes, which in turn may accelerate soil organic matter (SOM decomposition. We increased nutrient availability via fertilization to investigate the microbial response via soil enzyme activities. Specifically, we measured potential activities of seven enzymes at four temperatures in three soil profiles (organic, organic/mineral interface, and mineral from untreated native soils and from soils which had been fertilized with nitrogen (N and phosphorus (P since 1989 (23 years and 2006 (six years. Fertilized plots within the 1989 site received annual additions of 10 g N · m(-2 · year(-1 and 5 g P · m(-2 · year(-1. Within the 2006 site, two fertilizer regimes were established--one in which plots received 5 g N · m(-2 · year(-1 and 2.5 g P · m(-2 · year(-1 and one in which plots received 10 g N · m(-2 · year(-1 and 5 g P · m(-2 · year(-1. The fertilization treatments increased activities of enzymes hydrolyzing carbon (C-rich compounds but decreased phosphatase activities, especially in the organic soils. Activities of two enzymes that degrade N-rich compounds were not affected by the fertilization treatments. The fertilization treatments increased ratios of enzyme activities degrading C-rich compounds to those for N-rich compounds or phosphate, which could lead to changes in SOM chemistry over the long term and to losses of soil C. Accelerated SOM decomposition caused by increased nutrient availability could significantly offset predicted increased C fixation via stimulated net primary productivity in Arctic tundra ecosystems.

  15. Closed-loop deep brain stimulation by pulsatile delayed feedback with increased gap between pulse phases

    National Research Council Canada - National Science Library

    Oleksandr V Popovych; Borys Lysyansky; Peter A Tass

    2017-01-01

    Computationally it was shown that desynchronizing delayed feedback stimulation methods are effective closed-loop techniques for the control of synchronization in ensembles of interacting oscillators...

  16. Anorectal stimulation causes increased colonic motor activity in subjects with spinal cord injury.

    Science.gov (United States)

    Korsten, Mark A; Singal, Ashwani K; Monga, Amit; Chaparala, Geeta; Khan, Amir M; Palmon, Ron; Mendoza, John Reagan D; Lirio, Juan P; Rosman, Alan S; Spungen, Ann; Bauman, William A

    2007-01-01

    Difficulty with evacuation (DWE) is a major problem after spinal cord injury (SCI). Stimulation of the anal canal and lower rectum, accomplished using a gloved finger (so-called digital rectal stimulation or DRS) is often used as an adjunct to laxatives and enemas to facilitate bowel evacuation. However, the basis for the efficacy of DRS is not known. This study assessed the effect of DRS on colonic motility. Six subjects with SCI were studied several hours after a bowel care session. Colonic motility was assessed using a manometric catheter (affixed endoscopically to the splenic flexure) at baseline, during DRS, and after DRS. In addition, evacuation of barium oatmeal paste (with the consistency of stool and introduced into the rectum and descending colon) was assessed simultaneously using fluoroscopic techniques. The mean number (+/- SEM) of peristaltic waves per minute increased from 0 at baseline to 1.9 (+/- 0.5/min) during DRS and 1.5 (+/- 0.3/min) during the period immediately after cessation of DRS (P < 0.05). The mean amplitude (+/- SEM) of the peristaltic contractions was 43.4 (+/- 2.2) mmHg. The frequency of contractions, as well as amplitude of contractions, during or immediately after DRS was not significantly different. These manometric changes in response to DRS were accompanied by expulsion of barium oatmeal paste in every subject by the fifth DRS. DRS causes left-sided colonic activity in subjects with SCI. At least in part, an anorectal colonic reflex that results in enhanced contractions of the descending colon and rectum may contribute to bowel evacuation in individuals with SCI.

  17. Whole-hand water flow stimulation increases motor cortical excitability: a study of transcranial magnetic stimulation and movement-related cortical potentials.

    Science.gov (United States)

    Sato, Daisuke; Yamashiro, Koya; Onishi, Hideaki; Yasuhiro, Baba; Shimoyama, Yoshimitsu; Maruyama, Atsuo

    2015-02-01

    Previous studies examining the influence of afferent stimulation on corticospinal excitability have demonstrated that the intensity of afferent stimulation and the nature of the afferents targeted (cutaneous/proprioceptive) determine the effects. In this study, we assessed the effects of whole-hand water immersion (WI) and water flow stimulation (WF) on corticospinal excitability and intracortical circuits by measuring motor evoked potential (MEP) recruitment curves and conditioned MEP amplitudes. We further investigated whether whole-hand WF modulated movement-related cortical activity. Ten healthy subjects participated in three experiments, comprising the immersion of participants' right hands with (whole-hand WF) or without (whole-hand WI) water flow, and no immersion (control). We evaluated MEP recruitment curves produced by a single transcranial magnetic stimulation (TMS) pulse at increasing stimulus intensities, short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF) using the paired TMS technique before and after 15 min of intervention. Movement-related cortical potentials (MRCPs) were evaluated to examine primary motor cortex, supplementary motor area, and somatosensory cortex excitability upon movement before and after whole-hand WF. After whole-hand WF, the slope of the MEP recruitment curve significantly increased, whereas SICI decreased and ICF increased in the contralateral motor cortex. The amplitude of the Bereitschaftspotential, negative slope, and motor potential of MRCPs significantly increased after whole-hand WF. We demonstrated that whole-hand WF increased corticospinal excitability, decreased SICI, and increased ICF, although whole-hand WI did not change corticospinal excitability and intracortical circuits. Whole-hand WF modulated movement-related cortical activity, increasing motor cortex activation for the planning and execution of voluntary movements. Copyright © 2015 the American Physiological Society.

  18. Increasing carbon availability stimulates growth and secondary metabolites via modulation of phytohormones in winter wheat.

    Science.gov (United States)

    Huang, Jianbei; Reichelt, Michael; Chowdhury, Somak; Hammerbacher, Almuth; Hartmann, Henrik

    2017-02-01

    Phytohormones play important roles in plant acclimation to changes in environmental conditions. However, their role in whole-plant regulation of growth and secondary metabolite production under increasing atmospheric CO2 concentrations ([CO2]) is uncertain but crucially important for understanding plant responses to abiotic stresses. We grew winter wheat (Triticum aestivum) under three [CO2] (170, 390, and 680 ppm) over 10 weeks, and measured gas exchange, relative growth rate (RGR), soluble sugars, secondary metabolites, and phytohormones including abscisic acid (ABA), auxin (IAA), jasmonic acid (JA), and salicylic acid (SA) at the whole-plant level. Our results show that, at the whole-plant level, RGR positively correlated with IAA but not ABA, and secondary metabolites positively correlated with JA and JA-Ile but not SA. Moreover, soluble sugars positively correlated with IAA and JA but not ABA and SA. We conclude that increasing carbon availability stimulates growth and production of secondary metabolites via up-regulation of auxin and jasmonate levels, probably in response to sugar-mediated signalling. Future low [CO2] studies should address the role of reactive oxygen species (ROS) in leaf ABA and SA biosynthesis, and at the transcriptional level should focus on biosynthetic and, in particular, on responsive genes involved in [CO2]-induced hormonal signalling pathways. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  19. Increased fetal myocardial sensitivity to insulin-stimulated glucose metabolism during ovine fetal growth restriction.

    Science.gov (United States)

    Barry, James S; Rozance, Paul J; Brown, Laura D; Anthony, Russell V; Thornburg, Kent L; Hay, William W

    2016-04-01

    Unlike other visceral organs, myocardial weight is maintained in relation to fetal body weight in intrauterine growth restriction (IUGR) fetal sheep despite hypoinsulinemia and global nutrient restriction. We designed experiments in fetal sheep with placental insufficiency and restricted growth to determine basal and insulin-stimulated myocardial glucose and oxygen metabolism and test the hypothesis that myocardial insulin sensitivity would be increased in the IUGR heart. IUGR was induced by maternal hyperthermia during gestation. Control (C) and IUGR fetal myocardial metabolism were measured at baseline and under acute hyperinsulinemic/euglycemic clamp conditions at 128-132 days gestation using fluorescent microspheres to determine myocardial blood flow. Fetal body and heart weights were reduced by 33% (P = 0.008) and 30% (P = 0.027), respectively. Heart weight to body weight ratios were not different. Basal left ventricular (LV) myocardial blood flow per gram of LV tissue was maintained in IUGR fetuses compared to controls. Insulin increased LV myocardial blood flow by ∼38% (P IUGR fetuses was 73% greater than controls. Similar to previous reports testing acute hypoxia, LV blood flow was inversely related to arterial oxygen concentration (r(2 )= 0.71) in both control and IUGR animals. Basal LV myocardial glucose delivery and uptake rates were not different between IUGR and control fetuses. Insulin increased LV myocardial glucose delivery (by 40%) and uptake (by 78%) (P IUGR fetuses compared to controls. During basal and hyperinsulinemic-euglycemic clamp conditions LV myocardial oxygen delivery, oxygen uptake, and oxygen extraction efficiency were not different between groups. These novel results demonstrate that the fetal heart exposed to nutrient and oxygen deprivation from placental insufficiency appears to maintain myocardial energy supply in the IUGR condition via increased glucose uptake and metabolic response to insulin, which support

  20. IL-21 Is Increased in Nasal Polyposis and after Stimulation with Staphylococcus aureus Enterotoxin B.

    Science.gov (United States)

    Calus, Lien; Derycke, Lara; Dullaers, Melissa; Van Zele, Thibaut; De Ruyck, Natalie; Pérez-Novo, Claudina; Holtappels, Gabriele; De Vos, Geert; Lambrecht, Bart N; Bachert, Claus; Gevaert, Philippe

    2017-01-01

    Chronic rhinosinusitis with nasal polyposis (CRSwNP) is an inflammatory disease associated with lymphoid aggregates and local IgE production related to Staphylococcus aureus enterotoxins. T-follicular helper cells and their effector cytokine interleukin (IL)-21 play an important role in germinal center proliferation. IL-21 was determined on the mRNA level by qPCR in nasal tissue of 3 groups of patients: control (n = 17), chronic rhinosinusitis without nasal polyposis (CRSsNP; n = 23), and CRSwNP (n = 35). The expression of IL-21 by CD4+ T cells was analyzed in tissue at baseline and after 24-h stimulation of tissue fragments with S. aureus enterotoxin B (SEB) using flow cytometry. Finally, human nasal IL-21+CXCR5+CD4+ T cells were isolated and coincubated with human blood naive B cells to investigate their functionality. IL-21 mRNA expression was increased in the CRSwNP group (p B-cell lymphoma-6 and B-lymphocyte-induced maturation protein-1 were upregulated in CRSwNP versus CRSsNP. Furthermore, SEB was able to increase IL-21 mRNA expression significantly (p B cells. IL-21- and IL-21-producing CD4+ T cells were increased in CRSwNP. In addition, SEB induced an increase in IL-21 and IL-21+CD4+ T cells, suggesting that S. aureus can modulate the function of Tfh cells in nasal polyps. We speculate that T-follicular helper cells and IL-21 are important in the pathophysiology of CRSwNP. © 2017 S. Karger AG, Basel.

  1. THE INCREASING OF PRESCHOOL MULTIPLE INTELLIGENCES BY EDUCATIVE PLAYING INSTRUMENT STIMULATION

    Directory of Open Access Journals (Sweden)

    Yuni Sufyanti Arief

    2017-04-01

    Full Text Available Introduction: Multiple Intelligences can be incresed by playing stimulation with educative playing instrument. Educative playing is the activity that uses educate ways and instrument. Educative playing very important to increase speech development, cognitive, socialisation with the environment and also increse the streght and skill of child’s body. Method: Design used in this study was quasy experiment design. The population was preschool children 4–5 years old in working area of Mojo Public Health Centre of Surabaya. The sample was preschool children 4–5 years old that spesific in inclution criteria of this study. Data were analyzed by wilcoxon signed rank test to compare the ordinal data pre and post intervention and mann withney u-test that compare between intervention group and control  group with level of signifi cance of α ≤ 0.05. Result: The result of speech development that analyzed by Wilcoxon signed rank test showed that controlled group had p = 0.157 and intervention group had p = 0.005 and the result of mann whitney test was p = 0.03. The result of kinesthetic development by wilcoxon signed rank test showed that controlled group has p = 0.317 and intervention group has p = 0.005, and analyzed by mann whitney test in kinesthetic development showed the result of p = 0.02. Discussion: Educative playing instrument (picture cards, play dough, origami and meronce increased speech and fine motoric development of preschool children 4–5 years old in Mojo Indah Kindergarten of Surabaya. Educative playing instrument is the activity that makes the playing function optimally in child development and this activity can increase the child development such as physical, speech, cognitive and social adaptation.

  2. Vagus nerve stimulation increases energy expenditure: relation to brown adipose tissue activity.

    Directory of Open Access Journals (Sweden)

    Guy H E J Vijgen

    Full Text Available Human brown adipose tissue (BAT activity is inversely related to obesity and positively related to energy expenditure. BAT is highly innervated and it is suggested the vagus nerve mediates peripheral signals to the central nervous system, there connecting to sympathetic nerves that innervate BAT. Vagus nerve stimulation (VNS is used for refractory epilepsy, but is also reported to generate weight loss. We hypothesize VNS increases energy expenditure by activating BAT.Fifteen patients with stable vns therapy (age: 45 ± 10 yrs; body mass index; 25.2 ± 3.5 kg/m(2 were included between January 2011 and June 2012. Ten subjects were measured twice, once with active and once with inactivated VNS. Five other subjects were measured twice, once with active VNS at room temperature and once with active VNS under cold exposure in order to determine maximal cold-induced BAT activity. BAT activity was assessed by 18-Fluoro-Deoxy-Glucose-Positron-Emission-Tomography-and-Computed-Tomography. Basal metabolic rate (BMR was significantly higher when VNS was turned on (mean change; +2.2%. Mean BAT activity was not significantly different between active VNS and inactive VNS (BAT SUV(Mean; 0.55 ± 0.25 versus 0.67 ± 0.46, P = 0.619. However, the change in energy expenditure upon VNS intervention (On-Off was significantly correlated to the change in BAT activity (r = 0.935, P<0.001.VNS significantly increases energy expenditure. The observed change in energy expenditure was significantly related to the change in BAT activity. This suggests a role for BAT in the VNS increase in energy expenditure. Chronic VNS may have a beneficial effect on the human energy balance that has potential application for weight management therapy.The study was registered in the Clinical Trial Register under the ClinicalTrials.gov Identifier NCT01491282.

  3. Increased Vitreous Shedding of Microparticles in Proliferative Diabetic Retinopathy Stimulates Endothelial Proliferation

    Science.gov (United States)

    Chahed, Sadri; Leroyer, Aurélie S.; Benzerroug, Mounir; Gaucher, David; Georgescu, Adriana; Picaud, Serge; Silvestre, Jean-Sébastien; Gaudric, Alain; Tedgui, Alain; Massin, Pascale; Boulanger, Chantal M.

    2010-01-01

    OBJECTIVE Diabetic retinopathy is associated with progressive retinal capillary activation and proliferation, leading to vision impairment and blindness. Microparticles are submicron membrane vesicles with biological activities, released following cell activation or apoptosis. We tested the hypothesis that proangiogenic microparticles accumulate in vitreous fluid in diabetic retinopathy. RESEARCH DESIGN AND METHODS Levels and cellular origin of vitreous and plasma microparticles from control (n = 26) and diabetic (n = 104) patients were analyzed by flow cytometry, and their proangiogenic activity was assessed by in vitro thymidine incorporation and neovessel formation in subcutaneous Matrigel plugs in mice. RESULTS Microparticles of endothelial, platelet, photoreceptor, and microglial origin were identified in vitreous samples. Levels of photoreceptor and microglial microparticles were undetectable in plasmas but were comparable in diabetic and control vitreous samples. Vitreous platelet and endothelial microparticles levels were increased in diabetic patients and decreased following panretinal laser photocoagulation or intravitreal antivascular endothelial growth factor injection in proliferative diabetic retinopathy (PDR). The ratio of vitreous to plasma microparticle levels was calculated to estimate local formation versus potential plasma leakage. In PDR, the endothelial microparticles ratio—but not that for platelet—was greater than 1.0, indicating local formation of endothelial microparticles from retinal vessels and permeation of platelet microparticles from plasma. Isolated vitreous microparticles stimulated by 1.6-fold endothelial proliferation and increased new vessel formation in mice. CONCLUSIONS The present study demonstrates that vitreous fluid contains shed membrane microparticles of endothelial, platelet, and retinal origin. Vitreous microparticles levels are increased in patients with diabetic retinopathy, where they could contribute to disease

  4. Does the Longer Application of Anodal-Transcranial Direct Current Stimulation Increase Corticomotor Excitability Further? A Pilot Study

    Directory of Open Access Journals (Sweden)

    Shapour Jaberzadeh

    2012-09-01

    Full Text Available Introduction: Anodal transcranial direct current stimulation (a-tDCS of the primary motor cortex (M1 has been shown to be effective in increasing corticomotor excitability.Methods: We investigated whether longer applications of a-tDCS coincide with greater increases in corticomotor excitability compared to shorter application of a-tDCS. Ten right-handed healthy participants received one session of a-tDCS(1mA current with shorter (10 min and longer (10+10 min stimulation durationsapplied to the left M1 of extensor carpi radialis muscle (ECR. Corticomotorexcitability following application of a-tDCS was assessed at rest with transcranial magnetic stimulation (TMS elicited motor evoked otentials (MEP and compared with baseline data for each participant.Results: MEP amplitudes were increased following 10 min of a-tDCS by 67%(p = 0.001 with a further increase (32% after the second 10 min of a-tDCS (p = 0.005. MEP amplitudes remained elevated at 15 min post stimulation compared to baseline values by 65% (p = 0.02.Discussion: The results demonstrate that longer application of a-tDCS within the recommended safety limits, increases corticomotor excitability with after effects of up to 15 minutes post stimulation.

  5. Deep brain stimulation increases impulsivity in two patients with obsessive-compulsive disorder

    NARCIS (Netherlands)

    Luigjes, Judy; Mantione, Mariska; van den Brink, Wim; Schuurman, P. Richard; van den Munckhof, Pepijn; Denys, Damiaan

    2011-01-01

    Deep brain stimulation (DBS) is an adjustable, reversible, nondestructive neurosurgical intervention using implanted electrodes to deliver electrical pulses to areas in the brain. DBS has recently shown promising results as an experimental treatment of refractory obsessive-compulsive disorder (OCD).

  6. Hypertrophic Olivary Degeneration and Palatal or Oculopalatal Tremor

    Directory of Open Access Journals (Sweden)

    Caroline Tilikete

    2017-06-01

    Full Text Available Hypertrophic degeneration of the inferior olive is mainly observed in patients developing palatal tremor (PT or oculopalatal tremor (OPT. This syndrome manifests as a synchronous tremor of the palate (PT and/or eyes (OPT that may also involve other muscles from the branchial arches. It is associated with hypertrophic inferior olivary degeneration that is characterized by enlarged and vacuolated neurons, increased number and size of astrocytes, severe fibrillary gliosis, and demyelination. It appears on MRI as an increased T2/FLAIR signal intensity and enlargement of the inferior olive. There are two main conditions in which hypertrophic degeneration of the inferior olive occurs. The most frequent, studied, and reported condition is the development of PT/OPT and hypertrophic degeneration of the inferior olive in the weeks or months following a structural brainstem or cerebellar lesion. This “symptomatic” condition requires a destructive lesion in the Guillain–Mollaret pathway, which spans from the contralateral dentate nucleus via the brachium conjunctivum and the ipsilateral central tegmental tract innervating the inferior olive. The most frequent etiologies of destructive lesion are stroke (hemorrhagic more often than ischemic, brain trauma, brainstem tumors, and surgical or gamma knife treatment of brainstem cavernoma. The most accepted explanation for this symptomatic PT/OPT is that denervated olivary neurons released from inhibitory inputs enlarge and develop sustained synchronized oscillations. The cerebellum then modulates/accentuates this signal resulting in abnormal motor output in the branchial arches. In a second condition, PT/OPT and progressive cerebellar ataxia occurs in patients without structural brainstem or cerebellar lesion, other than cerebellar atrophy. This syndrome of progressive ataxia and palatal tremor may be sporadic or familial. In the familial form, where hypertrophic degeneration of the inferior olive may not

  7. Vagus nerve stimulation increases energy expenditure: relation to brown adipose tissue activity.

    Science.gov (United States)

    Vijgen, Guy H E J; Bouvy, Nicole D; Leenen, Loes; Rijkers, Kim; Cornips, Erwin; Majoie, Marian; Brans, Boudewijn; van Marken Lichtenbelt, Wouter D

    2013-01-01

    Human brown adipose tissue (BAT) activity is inversely related to obesity and positively related to energy expenditure. BAT is highly innervated and it is suggested the vagus nerve mediates peripheral signals to the central nervous system, there connecting to sympathetic nerves that innervate BAT. Vagus nerve stimulation (VNS) is used for refractory epilepsy, but is also reported to generate weight loss. We hypothesize VNS increases energy expenditure by activating BAT. Fifteen patients with stable vns therapy (age: 45 ± 10 yrs; body mass index; 25.2 ± 3.5 kg/m(2)) were included between January 2011 and June 2012. Ten subjects were measured twice, once with active and once with inactivated VNS. Five other subjects were measured twice, once with active VNS at room temperature and once with active VNS under cold exposure in order to determine maximal cold-induced BAT activity. BAT activity was assessed by 18-Fluoro-Deoxy-Glucose-Positron-Emission-Tomography-and-Computed-Tomography. Basal metabolic rate (BMR) was significantly higher when VNS was turned on (mean change; +2.2%). Mean BAT activity was not significantly different between active VNS and inactive VNS (BAT SUV(Mean); 0.55 ± 0.25 versus 0.67 ± 0.46, P = 0.619). However, the change in energy expenditure upon VNS intervention (On-Off) was significantly correlated to the change in BAT activity (r = 0.935, Penergy expenditure. The observed change in energy expenditure was significantly related to the change in BAT activity. This suggests a role for BAT in the VNS increase in energy expenditure. Chronic VNS may have a beneficial effect on the human energy balance that has potential application for weight management therapy. The study was registered in the Clinical Trial Register under the ClinicalTrials.gov Identifier NCT01491282.

  8. Repeated chlorpromazine administration increases a behavioural response of rats to 5-hydroxytryptamine receptor stimulation.

    Science.gov (United States)

    Green, A R

    1977-01-01

    1 The hyperactivity syndrome produced in rats by administration of tranylcypromine (20 mg/kg i.p.) followed 30 min later by L-tryptophan (50 mg/kg i.p.) is generally considered to be due to increased 5-hydroxytryptamine (5-HT) functional activity. It is inhibited by chlorpromazine (30 mg/kg i.p.) injected 60 min before the tranylcypromine. However, chlorpromazine injection for 4 days either at a dose of 30 mg/kg once daily or 5 mg/kg twice daily results in an enhanced hyperactivity response to tranylcypromine and L-tryptophan administration 24 h after the final dose of chlorpromazine. 2 One injection of chlorpromazine (30 mg/kg) did not produce enhancement 24 h later and the inhibition of the tranylcypromine/L-tryptophan hyperactivity observed after acute chlorpromazine injection was seen if the rats were given tranylcypromine and L-tryptophan 1 h after the fourth chlorpromazine (30 mg/kg) dose. 3 Chlorpromazine (30 mg/kg) once daily or 5 mg/kg twice daily for 4 days resulted in rats displaying enhanced behavioral responses to the suggested 5-HT agonist 5-methoxy N,N-dimethyltryptamine (2 mg/kg) on day 5. 4 Chlorpromazine (30 mg/kg) once daily for 4 days produces a slight increase in brain 5-hydroxytryptamine (5-HT) concentration on day 5, but no difference in the rate of brain 5-HT synthesis or the rate of 5-HT accumulation after tranylcypromine and L-tryptophan administration. 5. There is some evidence that chlorpromazine blocks 5-HT receptors. It has also been observed that several other neuroleptic drugs do not produce enhanced 5-HT responses after repeated administration. It is suggested therefore that the enhanced behavioural response to 5-HT receptor stimulation following repeated chlorpromazine administration may be because this drug blocks 5-HT receptors. PMID:264797

  9. Right ventricular involvement in feline hypertrophic cardiomyopathy.

    Science.gov (United States)

    Schober, K E; Savino, S I; Yildiz, V

    2016-12-01

    To evaluate right ventricular (RV) wall thickness and chamber dimensions in cats with hypertrophic cardiomyopathy (HCM). One hundred fifty-one healthy control cats and 200 cats with HCM. Retrospective, observational, clinical cohort study. Two-dimensional echocardiograms from all cats were analyzed. Right atrial diameter, RV free wall thickness, and RV chamber diameter were quantified using multiple imaging views. Conventional (mean ± 2 standard deviations) and allometrically scaled (Y = a × M b ) reference values were determined in normal cats and compared to values found in cats with HCM. Linear and logistic regression, multivariate regression, and mixed model analysis were performed to identify associations between RV wall thickness and severity of left ventricular (LV) hypertrophy, clinical severity of HCM, and presence of pleural effusion. Mean RV wall thickness was increased in HCM (p0.05) in control cats. Increased RV wall thickness is common in cats with HCM and relates to severity of LV hypertrophy and clinical status. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Brain State-Dependent Transcranial Magnetic Closed-Loop Stimulation Controlled by Sensorimotor Desynchronization Induces Robust Increase of Corticospinal Excitability.

    Science.gov (United States)

    Kraus, Dominic; Naros, Georgios; Bauer, Robert; Khademi, Fatemeh; Leão, Maria Teresa; Ziemann, Ulf; Gharabaghi, Alireza

    2016-01-01

    Desynchronization of sensorimotor rhythmic activity increases instantaneous corticospinal excitability, as indexed by amplitudes of motor-evoked potentials (MEP) elicited by transcranial magnetic stimulation (TMS). The accumulative effect of cortical stimulation in conjunction with sensorimotor desynchronization is, however, unclear. The aim of this study was to investigate the effects of repetitive pairing event-related desynchronization (ERD) with TMS of the precentral gyrus on corticospinal excitability. Closed-loop single-pulse TMS was controlled by beta-band (16-22 Hz) ERD during motor-imagery of finger extension and applied within a brain-computer interface environment in eleven healthy subjects. The same number and pattern of stimuli were applied in a control group of eleven subjects during rest, i.e. independent of ERD. To probe for plasticity resistant to depotentiation, stimulation protocols were followed by a depotentiation task. Brain state-dependent application of approximately 300 TMS pulses during beta-ERD resulted in a significant increase of corticospinal excitability. By contrast, the identical stimulation pattern applied independent of beta-ERD in the control experiment resulted in a decrease of corticospinal excitability. These effects persisted beyond the period of stimulation and the depotentiation task. These results could be instrumental in developing new therapeutic approaches such as the application of closed-loop stimulation in the context of neurorehabilitation. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. [Hypertrophic cardiomyopathy with left ventricular dilatation].

    Science.gov (United States)

    Iwami, G; Miyazaki, Y; Matsuyama, K; Shida, M; Ooga, M; Furuta, Y; Ikeda, H; Toshima, H; Chiba, M; Koga, Y

    1988-06-01

    There is increasing interest in the notion that some patients with hypertrophic cardiomyopathy (HCM) progress to morphological and functional manifestations similar to those of dilated cardiomyopathy (DCM). From 165 consecutive patients with HCM, 20 patients with left ventricular dilatation (left ventricular end-diastolic diameter greater than or equal to 50 mm) were selected and designated as dilated HCM. The diagnosis of HCM was established in these patients either by detection of the classical form of HCM in family members, with 2-dimensional echocardiographic evidence of asymmetric septal hypertrophy (ASH; septal thickness greater than or equal to 15 mm and a ratio of septal to posterior wall thickness greater than or equal to 1.3); or by demonstrating myocardial fiber disarray in autopsy or biopsy samples. The clinical manifestations of these patients with dilated HCM were then compared with those of other forms of HCM without left ventricular dilatation; 1) 40 patients with hypertrophic obstructive cardiomyopathy (HOCM) who had resting intraventricular pressure gradients of 20 mmHg or more, 2) 80 patients with non-obstructive HCM, each of whom had ASH of the entire ventricular septum (typical ASH), and 3) 25 non-obstructive patients whose hypertrophy was localized to the apical region of the ventricular septum (apical ASH). Patients having apical hypertrophy with a spade-like configuration on the left ventriculogram were excluded from the study. Compared with HOCM and typical ASH groups, the patients with dilated HCM had family histories of significantly more frequent HCM and less frequent hypertension. The patients with dilated HCM also had significantly less fractional shortening (FS), decreased interventricular septal thickness, greater left ventricular end-diastolic pressure (LVEDP), and left ventricular dilatation. During the follow-up period (average: 3.5 years), seven patients (35%) with dilated HCM died; five from congestive heart failure (CHF), one

  12. ß-Adrenergic stimulation increases RyR2 activity via intracellular Ca2+ and Mg2+ regulation.

    Directory of Open Access Journals (Sweden)

    Jiao Li

    Full Text Available Here we investigate how ß-adrenergic stimulation of the heart alters regulation of ryanodine receptors (RyRs by intracellular Ca(2+ and Mg(2+ and the role of these changes in SR Ca(2+ release. RyRs were isolated from rat hearts, perfused in a Langendorff apparatus for 5 min and subject to 1 min perfusion with 1 µM isoproterenol or without (control and snap frozen in liquid N2 to capture their phosphorylation state. Western Blots show that RyR2 phosphorylation was increased by isoproterenol, confirming that RyR2 were subject to normal ß-adrenergic signaling. Under basal conditions, S2808 and S2814 had phosphorylation levels of 69% and 15%, respectively. These levels were increased to 83% and 60%, respectively, after 60 s of ß-adrenergic stimulation consistent with other reports that ß-adrenergic stimulation of the heart can phosphorylate RyRs at specific residues including S2808 and S2814 causing an increase in RyR activity. At cytoplasmic [Ca(2+] 1 µM, ß-adrenergic stimulation only decreased cytoplasmic Mg(2+ and Ca(2+ inhibition of RyRs. The Ka and maximum levels of cytoplasmic Ca(2+ activation site were not affected by ß-adrenergic stimulation. Our RyR2 gating model was fitted to the single channel data. It predicted that in diastole, ß-adrenergic stimulation is mediated by 1 increasing the activating potency of Ca(2+ binding to the luminal Ca(2+ site and decreasing its affinity for luminal Mg(2+ and 2 decreasing affinity of the low-affinity Ca(2+/Mg(2+ cytoplasmic inhibition site. However in systole, ß-adrenergic stimulation is mediated mainly by the latter.

  13. Hypoxia Inhibits Hypertrophic Differentiation and Endochondral Ossification in Explanted Tibiae

    NARCIS (Netherlands)

    Leijten, Jeroen Christianus Hermanus; Moreira Teixeira, Liliana; Landman, Ellie; van Blitterswijk, Clemens; Karperien, Hermanus Bernardus Johannes

    2012-01-01

    Purpose: Hypertrophic differentiation of growth plate chondrocytes induces angiogenesis which alleviates hypoxia normally present in cartilage. In the current study, we aim to determine whether alleviation of hypoxia is merely a downstream effect of hypertrophic differentiation as previously

  14. Prevention and curative management of hypertrophic scar formation

    NARCIS (Netherlands)

    Bloemen, M.C.; Veer, van der W.M.; Ulrich, M.; Zuijlen, van P.P.; Niessen, F.B.; Middelkoop, E.

    2009-01-01

    Although hypertrophic scarring commonly occurs following burns, many aspects such as incidence of and optimal treatment for scar hypertrophy remain unclear. This review will focus on hypertrophic scar formation after burn in particular, exploring multiple treatment options and describing their

  15. MicroRNA-21 regulates hTERT via PTEN in hypertrophic scar fibroblasts.

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    Hua-Yu Zhu

    Full Text Available As an important oncogenic miRNA, microRNA-21 (miR-21 is associated with various malignant diseases. However, the precise biological function of miR-21 and its molecular mechanism in hypertrophic scar fibroblast cells has not been fully elucidated.Quantitative Real-Time PCR (qRT-PCR analysis revealed significant upregulation of miR-21 in hypertrophic scar fibroblast cells compared with that in normal skin fibroblast cells. The effects of miR-21 were then assessed in MTT and apoptosis assays through in vitro transfection with a miR-21 mimic or inhibitor. Next, PTEN (phosphatase and tensin homologue deleted on chromosome ten was identified as a target gene of miR-21 in hypertrophic scar fibroblast cells. Furthermore, Western-blot and qRT-PCR analyses revealed that miR-21 increased the expression of human telomerase reverse transcriptase (hTERT via the PTEN/PI3K/AKT pathway. Introduction of PTEN cDNA led to a remarkable depletion of hTERT and PI3K/AKT at the protein level as well as inhibition of miR-21-induced proliferation. In addition, Western-blot and qRT-PCR analyses confirmed that hTERT was the downstream target of PTEN. Finally, miR-21 and PTEN RNA expression levels in hypertrophic scar tissue samples were examined. Immunohistochemistry assays revealed an inverse correlation between PTEN and hTERT levels in high miR-21 RNA expressing-hypertrophic scar tissues.These data indicate that miR-21 regulates hTERT expression via the PTEN/PI3K/AKT signaling pathway by directly targeting PTEN, therefore controlling hypertrophic scar fibroblast cell growth. MiR-21 may be a potential novel molecular target for the treatment of hypertrophic scarring.

  16. Increased odds of live birth in fresh in vitro fertilization cycles with shorter ovarian stimulation.

    Science.gov (United States)

    Pereira, Nigel; Friedman, Caroline; Hutchinson, Anne P; Lekovich, Jovana P; Elias, Rony T; Rosenwaks, Zev

    2017-01-01

    To investigate the impact of prolonged ovarian stimulation on pregnancy outcomes in IVF cycles with fresh day 3 ET. Retrospective cohort study. University-affiliated center. All patients initiating their first IVF cycle with fresh day 3 ET. Prolonged ovarian stimulation was defined as a duration of more than two standard deviations (95th percentile) for the study cohort (i.e., >13 days). None. Live birth rate was considered the primary outcome and was compared between patients undergoing ovarian stimulation for ≤13 days and >13 days. Odds ratios (OR) with 95% confidence intervals (CI) for all pregnancy outcomes after day 3 ET were calculated. The OR for live birth was adjusted using logistic regression. A total of 6,410 and 339 patients underwent ovarian stimulation for ≤13 days and >13 days, respectively. There were no differences in the demographics or mean number of day 3 embryos transferred between the two groups. Ovarian stimulation ≤13 days was associated with increased odds of clinical pregnancy (OR 2.15, 95% CI 1.19-3.89) and live birth (OR 2.35, 95% CI 1.25-4.43). The increased odds for live birth in the ≤13-day group remained unchanged after logistic regression. Patients with clinical pregnancies in the >13-day group were younger (34.6 ± 4.91 years) compared with those who did not conceive (38.2 ± 4.72 years). Our findings suggest that ovarian stimulation ≤13 days is associated with increased odds of clinical pregnancy and live birth. In patients undergoing ovarian stimulation >13 days, younger age is associated with live birth. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  17. Apical Hypertrophic Cardiomyopathy in Association with PulmonaryArtery Hypertension

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    Mehdi Peighambari

    2012-09-01

    Full Text Available Apical Hypertrophic Cardiomyopathy is an uncommon condition constituting 1% -2% of the cases with Hypertrophic Cardiomyopathy (HCM diagnosis. We interestingly report two patients with apical hypertrophic cardiomyopathy in association with significant pulmonary artery hypertension without any other underlying reason for pulmonary hypertension. The patients were assessed by echocardiography, cardiac catheterization and pulmonary function parameters study.

  18. Apical Hypertrophic Cardiomyopathy in Association with Pulmonary Artery Hypertension

    OpenAIRE

    Peighambari, Mehdi; Parsaei, Mozghan; Sadeghpour, Anita; Alizadehasl, Azin

    2012-01-01

    Apical Hypertrophic Cardiomyopathy is an uncommon condition constituting 1% -2% of the cases with Hypertrophic Cardiomyopathy (HCM) diagnosis. We interestingly report two patients with apical hypertrophic cardiomyopathy in association with significant pulmonary artery hypertension without any other underlying reason for pulmonary hypertension. The patients were assessed by echocardiography, cardiac catheterization and pulmonary function parameters study.

  19. WF10 Stimulates NK Cell Cytotoxicity by Increasing LFA-1-Mediated Adhesion to Tumor Cells

    Directory of Open Access Journals (Sweden)

    Louisa Kühne

    2011-01-01

    Full Text Available The redox-active chlorite-based drug WF10 (Immunokine was shown to have modulatory effects on both the innate and adaptive immune system in vitro and in vivo. Animal studies suggest that WF10 enhances immunity against tumors. One possible explanation for such an effect is that WF10 stimulates natural killer cell cytotoxicity against malignant cells. Here, we show that WF10 regulates human NK cell cytotoxicity in a time-dependent manner, following an S-shaped kinetic with an initial stimulation of activity followed by a decrease in activity relative to the untreated controls. WF10 does not activate NK cells on its own but co-stimulates NK cell activation mediated by different activating receptors. This is mediated by enhancing NK cell adhesion to target cells through promoting the activation of the integrin LFA-1. These data demonstrate a direct effect of WF10 on the cytotoxicity of human NK cells.

  20. The increase of alpha-melanocyte-stimulating hormone in the plasma of chronic fatigue syndrome patients

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    Shishioh-Ikejima Nobue

    2010-08-01

    Full Text Available Abstract Background Despite extensive research, no reliable biological marker for chronic fatigue syndrome (CFS has yet been identified. However, hyperactivation of melanotrophs in the pituitary gland and increased levels of plasma alpha-melanocyte-stimulating hormone (α-MSH have recently been detected in an animal model of chronic stress. Because CFS is considered to be caused partly by chronic stress events, increased α-MSH plasma levels may also occur in CFS patients. We therefore examined α-MSH levels in CFS patients. Methods Fifty-five CFS patients, who were previously diagnosed within 10 years of with the disease, were enrolled in this study. Thirty healthy volunteers were studied as controls. Fasting bloods samples were collected in the morning and evaluated for their plasma levels of α-MSH, adrenocorticotropic hormone (ACTH, serum cortisol and dehydroepiandrosterone sulfate (DHEA-S. Mean levels of α-MSH were compared between the CFS and control groups using Welch's t test. Results The mean plasma α-MSH concentration in the CFS group (17.9 ± 1.0 pg/mL was significantly higher than that in healthy controls (14.5 ± 1.0 pg/mL, p = 0.02. However, there was a wide range of values in the CFS group. The factors correlated with the plasma α-MSH values were analyzed using Spearman's rank correlation. A negative correlation was found between the duration of the CFS and the plasma α-MSH values (p = 0.04, rs = -0.28, but no correlations with ACTH, cortisol or DHEA-S levels were identified (p = 0.55, 0.26, 0.33, respectively. The CFS patients were divided into two groups: patients diagnosed for ≤ 5 years' duration, and those diagnosed for 5-10 years' duration. They were compared with the healthy controls using one-way ANOVA and Tukey-Kramer multiple comparison tests. The mean α-MSH concentration in the ≤ 5 years group was 20.8 ± 1.2 pg/mL, which was significantly higher than that in the healthy controls (p Conclusions CFS patients with

  1. Chronic hypertrophic cranial pachymeningitis associated with HTLV-I infection.

    Science.gov (United States)

    Kawano, Y; Kira, J

    1995-10-01

    Two patients presenting with recurrent multiple cranial neuropathy showed diffuse thickening and gadolinium enhancement of the dura mater on brain MRI. Both had anti-HTLV-I antibodies in serum. A quantitative polymerase chain reaction study of the peripheral blood disclosed that the HTLV-I proviral DNA loads increased considerably in one case and moderately in the other. Both showed a spontaneous proliferation of peripheral blood lymphocytes as well as an increase in helper/inducer T cells. Neither had any other underlying infections or autoimmune diseases. Thus it is possible that hypertrophic pachymeningitis developed as a result of multiorgan involvement of HTLV-I infection in these patients.

  2. Comparison of intralesional verapamil with intralesional triamcinolone in the treatment of hypertrophic scars and keloids

    Directory of Open Access Journals (Sweden)

    Margaret Shanthi F

    2008-01-01

    Full Text Available Background : The calcium channel blocker, verapamil stimulates procollagenase synthesis in keloids and hypertrophic scars. Aim : To study the effect of verapamil in the treatment of hypertrophic scars and keloids and to evaluate the effect of verapamil on the rate of reduction of hypertrophic scars and keloids in comparison with triamcinolone. Methods : The study was a randomized, single blind, parallel group study in which 54 patients were allocated to to receive either verapamil or triamcinolone. Drugs were administered intralesionally in both groups. Improvement of the scar was measured using modified Vancouver scale and by using a centimeter scale serially till the scar flattened. Results : There was a reduction in vascularity, pliability, height and width of the scar with both the drugs after 3 weeks of treatment. These changes were present at one year of follow-up after stopping treatment. Scar pigmentation was not changed desirably by either drug. Length of the scars was also not altered significantly by either drug. The rate of reduction in vascularity, pliability, height and width of the scar with triamcinolone was faster than with verapamil. Adverse drug reactions were more with triamcinolone than with verapamil. Conclusion : Intralesional verapamil may be a suitable alternative to triamcinolone in the treatment of hypertrophic scars and keloids.

  3. Mechanical stimulation evokes rapid increases in extracellular adenosine concentration in the prefrontal cortex

    Science.gov (United States)

    Ross, Ashley E.; Nguyen, Michael D.; Privman, Eve; Venton, B. Jill

    2014-01-01

    Mechanical perturbations can release ATP, which is broken down to adenosine. In this work, we used carbon-fiber microelectrodes and fast-scan cyclic voltammetry to measure mechanically-stimulated adenosine in the brain by lowering the electrode 50 μm. Mechanical stimulation evoked adenosine in vivo (average: 3.3 ± 0.6 μM) and in brain slices (average: 0.8 ± 0.1 μM) in the prefrontal cortex. The release was transient, lasting 18 ± 2 s. Lowering a 15 μm diameter glass pipette near the carbon-fiber microelectrode produced similar results as lowering the actual microelectrode. However, applying a small puff of artificial cerebral spinal fluid was not sufficient to evoke adenosine. Multiple stimulations within a 50 μm region of a slice did not significantly change over time or damage cells. Chelating calcium with EDTA or blocking sodium channels with tetrodotoxin (TTX) significantly decreased mechanically evoked adenosine, signifying that the release is activity-dependent. An alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), did not affect mechanically-stimulated adenosine; however, the nucleoside triphosphate diphosphohydrolase 1,2 and 3 (NTDPase) inhibitor POM-1 significantly reduced adenosine so a portion of adenosine is dependent on extracellular ATP metabolism. Thus, mechanical perturbations from inserting a probe in the brain cause rapid, transient adenosine signaling which might be neuroprotective. PMID:24606335

  4. Multimodality imaging in apical hypertrophic cardiomyopathy

    Science.gov (United States)

    Parisi, Rosario; Mirabella, Francesca; Secco, Gioel Gabrio; Fattori, Rossella

    2014-01-01

    Apical hypertrophic cardiomyopathy (AHCM) is a relatively rare morphologic variant of HCM in which the hypertrophy of myocardium is localized to the left ventricular apex. Symptoms of AHCM might vary from none to others mimic coronary artery disease including acute coronary syndrome, thus resulting in inappropriate hospitalization. Transthoracic echocardiography is the first-line imaging technique for the diagnosis of hypertrophic cardiomyopathies. However, when the hypertrophy of the myocardium is localized in the ventricular apex might results in missed diagnosis. Aim of this paper is to review the different imaging techniques used for the diagnosis of AHCM and their role in the detection and comprehension of this uncommon disease. PMID:25276293

  5. On the surgical treatment of hypertrophic scars: a comprehensive guideline for the surgical treatment of hypertrophic scars

    NARCIS (Netherlands)

    Stekelenburg, C.M.; van der Wal, M.B.A.; Middelkoop, E.; Niessen, F.B.; van Zuijlen, P.P.M.

    2012-01-01

    Background: Treating the hypertrophic scar remains a challenging problem. It often leaves the clinician with the questions whether, when and how to treat a hypertrophic scar. Methods: This review will focus on the surgical treatment of hypertrophic scars considering the latest research in this

  6. Amygdala electrical stimulation inducing spatial memory recovery produces an increase of hippocampal bdnf and arc gene expression.

    Science.gov (United States)

    Mercerón-Martínez, D; Almaguer-Melian, W; Alberti-Amador, E; Estupiñán, B; Fernández, I; Bergado, J A

    2016-06-01

    Amygdala seems to promote the consolidation of plastic modification in different brain areas and these long-term brain changes require a rapid de novo RNA and protein synthesis. We have previously shown that basolateral amygdala electrical stimulation produces a partial recovery of spatial memory in fimbria-fornix lesioned animals and it is also able to increase the BDNF protein content in the hippocampus. The emerging question is whether these increased BDNF protein content arises from previously synthesized RNA or from de novo RNA expression. Now we address the question if amygdala electrical stimulation 15min after daily water maze training produces a rapid de novo RNA synthesis in the hippocampus, a critical brain area for spatial memory recovery in fimbria-fornix lesioned animals. In addition, we also study RNA arc expression, a gene which is essential for memory and neural plasticity processes. To this purpose, we study amygdala stimulation effects on the expression of plasticity related-early-genes bdnf and arc in the hippocampus of fimbria-fornix lesioned animals trained in a water-maze for 4days. We also checked on the expression of both genes in non-lesioned, untrained animals (acute condition) at 0.5, 1, 2 and 24h after basolateral amygdala electrical stimulation. Our data from trained animals confirm that daily amygdala electrical stimulation 15min after water maze training produces a partial memory recovery and that is coupled to an increase of bdnf and arc genes expression in the hippocampus. Additionally, the acute study shows that a single session of amygdala stimulation induces a transient increase of both genes (peaking at 30min). These results confirm the memory improving effect of amygdala stimulation in fimbria-fornix-lesioned animals and sustain the assumption that the memory improving effect is mediated by newly synthetized BDNF acting on a memory relevant structure like the hippocampus. The increased amount of BDNF within the hippocampus

  7. Supraventricular arrhythmia as the cause of sudden death in hypertrophic cardiomyopathy.

    Science.gov (United States)

    Madariaga, I; Carmona, J R; Mateas, F R; Lezaun, R; de los Arcos, E

    1994-01-01

    Electrophysiological studies with simultaneous echocardiographic control and invasive measurement of intravascular pressures were carried out in a 13-year-old boy with hypertrophic cardiomyopathy who was hospitalized after an episode of aborted sudden death. Ventricular stimulation did not induce ventricular tachycardia, but atrial stimulation induced atrial fibrillation, atrial flutter and non-sustained ventricular tachycardia. Atrial stimulation (S1) at 200 beats.min-1 (10-15 s) also induced significant repolarization abnormalities in the 5-10 post-stimulation beats. Akinesia of the ventricular septum and posterior wall without opening of the mitral valve was documented by echocardiography. A complete anterior systolic motion, not observed under basal conditions, was detected in the first post-stimulation beat. Atrial stimulation at rates over 120 beats.min-1 caused a drop in systolic blood pressure, a rise in pulmonary artery pressure, and a decrease in cardiac output. Despite therapy with propranolol and amiodarone, the patient died suddenly.

  8. Increasing breadth of semantic associations with left frontopolar direct current brain stimulation: a role for individual differences.

    Science.gov (United States)

    Brunyé, Tad T; Moran, Joseph M; Cantelon, Julie; Holmes, Amanda; Eddy, Marianna D; Mahoney, Caroline R; Taylor, Holly A

    2015-03-25

    The aim of this study was to evaluate the influence of left frontopolar versus auditory (control) cortex transcranial direct current stimulation (tDCS) on the breadth of semantic associations produced in a cued free association task. A within-participants design administered anodal tDCS over the left frontopolar or auditory cortex, centered at electrode site AFZ or T7 using a 4×1 targeted stimulation montage. During stimulation, participants produced free associates in response to cues designed to promote narrow, moderate, or broad semantic associations. We measured the latent semantic associative strength of generated words relative to cues. The cue manipulation produced expected effects on the associative breadth of generated words, but there was no main effect of stimulation site, and calculated Bayes factors showed strong support for the null hypothesis. However, individual differences in creative potential, as assessed by the remote associates test, reliably and positively predicted increases in associative breadth under the frontopolar versus the auditory control condition, but only in response to narrow cues. In conclusion, the present data support neuroimaging studies demonstrating the involvement of left frontopolar cortical regions in generating relatively broad semantic associations. They also provide novel evidence that individual differences in creative potential may modulate the influence of brain stimulation on the breadth of generated semantic associations. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

  9. A Novel Magnetic Stimulator Increases Experimental Pain Tolerance in Healthy Volunteers - A Double-Blind Sham-Controlled Crossover Study

    Science.gov (United States)

    Kortekaas, Rudie; Konopka, Karl-Heinz; Harbers, Marten; van der Hoeven, Johannes H.; van Wijhe, Marten; Aleman, André; Maurits, Natasha M.

    2013-01-01

    The ‘complex neural pulse’TM (CNP) is a neuromodulation protocol employing weak pulsed electromagnetic fields (PEMF). A pioneering paper reported an analgesic effect in healthy humans after 30 minutes of CNP-stimulation using three nested whole head coils. We aimed to devise and validate a stimulator with a novel design entailing a multitude of small coils at known anatomical positions on a head cap, to improve applicability. The main hypothesis was that CNP delivery with this novel device would also increase heat pain thresholds. Twenty healthy volunteers were enrolled in this double-blind, sham-controlled, crossover study. Thirty minutes of PEMF (CNP) or sham was applied to the head. After one week the other treatment was given. Before and after each treatment, primary and secondary outcomes were measured. Primary outcome was heat pain threshold (HPT) measured with thermal quantitative sensory testing. Other outcomes were warmth detection threshold, and aspects of cognition, emotion and motor performance. As hypothesized heat pain threshold was significantly increased after the PEMF stimulation. All other outcomes were unaltered by the PEMF but there was a trend level reduction of cognitive performance after PEMF stimulation as measured by the digit-symbol substitution task. Results from this pilot study suggest that our device is able to stimulate the brain and to modulate its function. This is in agreement with previous studies that used similar magnetic field strengths to stimulate the brain. Specifically, pain control may be achieved with PEMF and for this analgesic effect, coil design does not appear to play a dominant role. In addition, the flexible configuration with small coils on a head cap improves clinical applicability. Trial Registration Dutch Cochrane Centre NTR1093 PMID:23620795

  10. A novel magnetic stimulator increases experimental pain tolerance in healthy volunteers - a double-blind sham-controlled crossover study.

    Directory of Open Access Journals (Sweden)

    Rudie Kortekaas

    Full Text Available UNLABELLED: The 'complex neural pulse'(TM (CNP is a neuromodulation protocol employing weak pulsed electromagnetic fields (PEMF. A pioneering paper reported an analgesic effect in healthy humans after 30 minutes of CNP-stimulation using three nested whole head coils. We aimed to devise and validate a stimulator with a novel design entailing a multitude of small coils at known anatomical positions on a head cap, to improve applicability. The main hypothesis was that CNP delivery with this novel device would also increase heat pain thresholds. Twenty healthy volunteers were enrolled in this double-blind, sham-controlled, crossover study. Thirty minutes of PEMF (CNP or sham was applied to the head. After one week the other treatment was given. Before and after each treatment, primary and secondary outcomes were measured. Primary outcome was heat pain threshold (HPT measured with thermal quantitative sensory testing. Other outcomes were warmth detection threshold, and aspects of cognition, emotion and motor performance. As hypothesized heat pain threshold was significantly increased after the PEMF stimulation. All other outcomes were unaltered by the PEMF but there was a trend level reduction of cognitive performance after PEMF stimulation as measured by the digit-symbol substitution task. Results from this pilot study suggest that our device is able to stimulate the brain and to modulate its function. This is in agreement with previous studies that used similar magnetic field strengths to stimulate the brain. Specifically, pain control may be achieved with PEMF and for this analgesic effect, coil design does not appear to play a dominant role. In addition, the flexible configuration with small coils on a head cap improves clinical applicability. TRIAL REGISTRATION: Dutch Cochrane Centre NTR1093.

  11. Histologic Sequelae of Apical Hypertrophic Cardiomyopathy: Dystrophic Calcification

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    Shahryar G Saba

    2017-05-01

    Full Text Available We present cardiac computed tomography (CT findings demonstrating apical hypertrophic cardiomyopathy with dystrophic calcification of the left ventricular apex. The absence of significant epicardial coronary artery disease demonstrated by coronary CT angiography suggests that increased wall tension and decreased microvascular perfusion over time account for the dyskinetic apical myocardium, rather than myocardial infarction secondary to atherosclerotic plaque rupture. These observations support CT as the imaging modality of choice to visualize the deposition of calcium in injured myocardial tissue, a recognized occurrence in chronically infarcted myocardium.

  12. Functional effects of losartan in hypertrophic cardiomyopathy

    DEFF Research Database (Denmark)

    Axelsson, Anna Karin Irene; Iversen, Kasper; Vejlstrup, Niels G.

    2016-01-01

    OBJECTIVE: There is a lack of disease-modifying treatments in hypertrophic cardiomyopathy (HCM). The aim of this randomised, placebo-controlled study was to assess if losartan could improve or ameliorate deterioration of cardiac function and exercise capacity. METHODS: Echocardiography, exercise...

  13. Fabry Disease in Families With Hypertrophic Cardiomyopathy

    DEFF Research Database (Denmark)

    Adalsteinsdottir, Berglind; Palsson, Runolfur; Desnick, Robert J

    2017-01-01

    BACKGROUND: The screening of Icelandic patients clinically diagnosed with hypertrophic cardiomyopathy resulted in identification of 8 individuals from 2 families with X-linked Fabry disease (FD) caused by GLA(α-galactosidase A gene) mutations encoding p.D322E (family A) or p.I232T (family B...

  14. Alcohol septal ablation for obstructive hypertrophic cardiomyopathy

    NARCIS (Netherlands)

    Steggerda, Robbert

    2015-01-01

    Hypertrophic cardiomyopathy is an inhered heart disease characterised by a thickened heart muscle, common in 1:500 persons. Obstruction of blood flow in the heart due the thickened heart muscle can occur and cause dyspnoea. A heart surgeon can cut away part of the thickened muscle (myectomy). With

  15. Hypertrophic Cardiomyopathy: Pathophysiology, Genetics and Invasive Treatment

    NARCIS (Netherlands)

    M. Michels (Michelle)

    2011-01-01

    textabstractHypertrophic cardiomyopathy (HCM) is the most common inheritable cardiac disorder with a phenotypic prevalence of 1:500. It is defined by the presence of left ventricular hypertrophy (LVH) in the absence of loading conditions (hypertension, valve disease) sufficient to cause the observed

  16. THE IMPACT OF FERTILIZATION AND FOLIAR STIMULATION PRODUCTS BOTH ON INCREASING THE RESISTANCE TO MAJOR PHYTOPATHOGENS ATTACKS, AND ON INCREASING THE QUANTITY AND QUALITY OF WINE GRAPES HARVEST

    Directory of Open Access Journals (Sweden)

    Cristina BUNESCU

    2014-12-01

    Full Text Available The paper aimed to demonstrate the impact of fertilization and foliar stimulation products both on increasing the resistance to major phytopathogens attacks, and on increasing the quantity and quality of wine grapes harvest. Applying the foliar fertilizer products Plonvit Kali (c1, Tytanit (c2 and Optysil (c3 to vines, for a period of three years (2011/2013, in phenophases of intensive growth of shoots and grapes at approved dosages, simultaneously with pesticide treatment, not only a reduction of pathogenic fungi attack was obtained, but also and an increase of harvest without diminishing the quality of the grapes.

  17. Stimulation of Mucin, Mucus, and Viscosity during Lubiprostone in Patients with Chronic Constipation may Potentially Lead to Increase of Lubrication.

    Science.gov (United States)

    Majewski, Marek; Sarosiek, Irene; Wallner, Grzegorz; Edlavitch, Stanley A; Sarosiek, Jerzy

    2014-12-18

    The purpose of this clinical trial was to explore whether lubiprostone increases the rate of mucus and mucin secretion and its viscosity in chronic constipation (CC) patients. The secretion of chloride (CS) into the gastrointestinal tract lumen is pivotal in the body's ability to process non-digestible food components. CS sets the optimal rate of hydration for non-digestible food components, their fluidity, and their adequate propulsion along the alimentary tract. Chloride is also instrumental in the secretion of alimentary tract mucus, and the formation of a gel-like, viscous mucus-buffer layer. This layer acts as the first line and vanguard of the mucosal barrier. This barrier is essential in mucosal lubrication and protection. Lubiprostone, a novel chloride channel stimulator ClC-2, is currently approved for the treatment of CC. Its impact on mucus, mucus secretion, and viscosity is not established. A double-blind, crossover trial was approved by the IRBs at the Kansas University Medical Center (Kansas City, KS) (study site) and at the Texas Tech University HSC (El Paso, TX) (analysis site). The study included 20 patients (17 females (F); mean age: 37 years) with symptoms of CC diagnosed according to the Rome III criteria. Patients were randomized to 1 week of therapy with lubiprostone or placebo followed by a 1 week washout and 1 week of the alternative therapy. Gastric juice was collected basally and during stimulation with pentagastrin (6 μg/kg body weight subcutaneously) at the end of weeks 1 and 3. Pentagastrin stimulation mimics food stimulation. The mucus content in gastric juice was assessed gravimetrically. The mucin content was measured after its purification using ultracentrifugation. The viscosity of the gastric secretion was measured using a digital viscometer. In comparison with placebo, the volume of gastric secretion in patients with CC during administration of lubiprostone increased significantly by 50% (86.3 vs. 57.5 ml/h) (Plubiprostone

  18. Quinapril treatment increases insulin-stimulated endothelial function and adiponectin gene expression in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Hermann, Thomas S; Li, Weijie; Dominguez, Helena

    2005-01-01

    OBJECTIVE: Angiotensin-converting enzyme inhibitors reduce cardiovascular mortality and improve endothelial function in type 2 diabetic patients. We hypothesized that 2 months of quinapril treatment would improve insulin-stimulated endothelial function and glucose uptake in type 2 diabetic subjects...... and simultaneously increase the expression of genes that are pertinent for endothelial function and metabolism. METHODS: Twenty-four type 2 diabetic subjects were randomized to receive 2 months of quinapril 20 mg daily or no treatment in an open parallel study. Endothelium-dependent and -independent vasodilation...... occlusion plethysmography. Gene expression was measured by real-time PCR. RESULTS: Quinapril treatment increased insulin-stimulated endothelial function in the type 2 diabetic subjects (P = 0.005), whereas forearm glucose uptake was unchanged. Endothelial function was also increased by quinapril (P = 0...

  19. Compression therapy affects collagen type balance in hypertrophic scar.

    Science.gov (United States)

    Tejiram, Shawn; Zhang, Jenny; Travis, Taryn E; Carney, Bonnie C; Alkhalil, Abdulnaser; Moffatt, Lauren T; Johnson, Laura S; Shupp, Jeffrey W

    2016-04-01

    The effects of pressure on hypertrophic scar are poorly understood. Decreased extracellular matrix deposition is hypothesized to contribute to changes observed after pressure therapy. To examine this further, collagen composition was analyzed in a model of pressure therapy in hypertrophic scar. Hypertrophic scars created on red Duroc swine (n = 8) received pressure treatment (pressure device mounting and delivery at 30 mm Hg), sham treatment (device mounting and no delivery), or no treatment for 2 wk. Scars were assessed weekly and biopsied for histology, hydroxyproline quantification, and gene expression analysis. Transcription levels of collagen precursors COL1A2 and COL3A1 were quantified using reverse transcription-polymerase chain reaction. Masson trichrome was used for general collagen quantification, whereas immunofluorescence was used for collagen types I and III specific quantification. Total collagen quantification using hydroxyproline assay showed a 51.9% decrease after pressure initiation. Masson trichrome staining showed less collagen after 1 (P < 0.03) and 2 wk (P < 0.002) of pressure application compared with sham and untreated scars. Collagen 1A2 and 3A1 transcript decreased by 41.9- and 42.3-fold, respectively, compared with uninjured skin after pressure treatment, whereas a 2.3- and 1.3-fold increase was seen in untreated scars. This decrease was seen in immunofluorescence staining for collagen types I (P < 0.001) and III (P < 0.04) compared with pretreated levels. Pressure-treated scars also had lower levels of collagen I and III after pressure treatment (P < 0.05) compared with sham and untreated scars. These results demonstrate the modulation of collagen after pressure therapy and further characterize its role in scar formation and therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Increasing Production from Low-Permeability Gas Reservoirs by Optimizing Zone Isolation for Successful Stimulation Treatments

    Energy Technology Data Exchange (ETDEWEB)

    Fred Sabins

    2005-03-31

    Maximizing production from wells drilled in low-permeability reservoirs, such as the Barnett Shale, is determined by cementing, stimulation, and production techniques employed. Studies show that cementing can be effective in terms of improving fracture effectiveness by 'focusing' the frac in the desired zone and improving penetration. Additionally, a method is presented for determining the required properties of the set cement at various places in the well, with the surprising result that uphole cement properties in wells destined for multiple-zone fracturing is more critical than those applied to downhole zones. Stimulation studies show that measuring pressure profiles and response during Pre-Frac Injection Test procedures prior to the frac job are critical in determining if a frac is indicated at all, as well as the type and size of the frac job. This result is contrary to current industry practice, in which frac jobs are designed well before the execution, and carried out as designed on location. Finally, studies show that most wells in the Barnett Shale are production limited by liquid invasion into the wellbore, and determinants are presented for when rod or downhole pumps are indicated.

  1. Increased electrical nerve stimulation threshold of the sciatic nerve in patients with diabetic foot gangrene: a prospective parallel cohort study.

    Science.gov (United States)

    Keyl, Cornelius; Held, Tanja; Albiez, Georg; Schmack, Astrid; Wiesenack, Christoph

    2013-07-01

    Peripheral neuropathy may affect nerve conduction in patients with diabetes mellitus. This study was designed to test the hypothesis that the electrical stimulation threshold for a motor response of the sciatic nerve is increased in patients suffering from diabetic foot gangrene compared to non-diabetic patients. Prospective non-randomised trial with two parallel groups. Two university-affiliated hospitals. Patients scheduled for surgical treatment of diabetic foot gangrene (n = 30) and non-diabetic patients (n = 30) displaying no risk factors for neuropathy undergoing orthopaedic foot or ankle surgery. The minimum current intensity required to elicit a typical motor response (dorsiflexion or eversion of the foot) at a pulse width of 0.1 ms and a stimulation frequency of 1 Hz when the needle tip was positioned under ultrasound control directly adjacent to the peroneal component of the sciatic nerve. The non-diabetic patients were younger [64 (SD 12) vs. 74 (SD 7) years] and predominantly female (23 vs. 8). The geometric mean of the motor stimulation threshold was 0.26 [95% confidence interval (95% CI) 0.24 to 0.28] mA in non-diabetic and 1.9 (95% CI 1.6 to 2.2) mA in diabetic patients. The geometric mean of the electrical stimulation threshold was significantly (P diabetic compared to non-diabetic patients. The electrical stimulation threshold for a motor response of the sciatic nerve is increased by a factor of 7.2 in patients with diabetic foot gangrene, which might hamper nerve identification.

  2. Herbivorous snails can increase water clarity by stimulating growth of benthic algae.

    Science.gov (United States)

    Zhang, Xiufeng; Taylor, William D; Rudstam, Lars G

    2017-11-01

    Eutrophication in shallow lakes is characterized by a switch from benthic to pelagic dominance of primary productivity that leads to turbid water, while benthification is characterized by a shift in primary production from the pelagic zone to the benthos associated with clear water. A 12-week mesocosm experiment tested the hypothesis that the herbivorous snail Bellamya aeruginosa stimulates the growth of pelagic algae through grazing on benthic algae and through accelerating nutrient release from sediment. A tube-microcosm experiment using 32P-PO4 as a tracer tested the effects of the snails on the release of sediment phosphorus (P). The mesocosm experiment recorded greater total nitrogen (TN) concentrations and a higher ratio of TN:TP in the overlying water, and a higher light intensity and biomass of benthic algae as measured by chlorophyll a (Chl a) in the snail treatment than in the control. Concentrations of total phosphorus (TP), total suspended solids (TSSs), and inorganic suspended solids (ISSs) in the overlying water were lower in the snail treatment than in the control, though no significant difference in Chl a of pelagic algae between the snail treatment and control was observed. In the microcosm experiment, 32P activity in the overlying water was higher in the snail treatment than in the control, indicating that snails accelerated P release from the sediment. Our interpretation of these results is that snails enhanced growth of benthic algae and thereby improved water clarity despite grazing on the benthic algae and enhancing P release from the sediment. The rehabilitation of native snail populations may therefore enhance the recovery of eutrophic shallow lakes to a clear water state by stimulating growth of benthic algae.

  3. Systolic anterior motion of the tricuspid valve in a patient with hypertrophic obstructive cardiomyopathy

    NARCIS (Netherlands)

    Farag, Emile S.; Planken, R. Nils; Boekholdt, S. Matthijs; Kluin, Jolanda

    2017-01-01

    Hypertrophic cardiomyopathy is a heterogeneous myocardial disease and is characterized by increased left ventricular wall thickness. Left ventricular outflow tract obstruction occurs in up to 70% of patients and is often caused by systolic anterior motion of the mitral valve, a paradoxical

  4. Obtaining insurance after DNA diagnostics : A survey among hypertrophic cardiomyopathy mutation carriers

    NARCIS (Netherlands)

    Christiaans, Imke; Kok, Tjitske M.; Van Langen, Irene M.; Birnie, Erwin; Bonsel, Gouke J.; Wilde, Arthur A. M.; Smets, Ellen M. A.

    2010-01-01

    Hypertrophic cardiomyopathy (HCM) is a common hereditary heart disease associated with increased mortality. Disclosure of DNA test results may have social implications such as low access to insurance. In the Netherlands, insurance companies are restricted in the use of genetic information of their

  5. Obtaining insurance after DNA diagnostics: a survey among hypertrophic cardiomyopathy mutation carriers

    NARCIS (Netherlands)

    Christiaans, Imke; Kok, Tjitske M.; van Langen, Irene M.; Birnie, Erwin; Bonsel, Gouke J.; Wilde, Arthur A. M.; Smets, Ellen M. A.

    2010-01-01

    Hypertrophic cardiomyopathy (HCM) is a common hereditary heart disease associated with increased mortality. Disclosure of DNA test results may have social implications such as low access to insurance. In the Netherlands, insurance companies are restricted in the use of genetic information of their

  6. High frequency somatosensory stimulation increases sensori-motor inhibition and leads to perceptual improvement in healthy subjects.

    Science.gov (United States)

    Rocchi, Lorenzo; Erro, Roberto; Antelmi, Elena; Berardelli, Alfredo; Tinazzi, Michele; Liguori, Rocco; Bhatia, Kailash; Rothwell, John

    2017-06-01

    High frequency repetitive somatosensory stimulation (HF-RSS), which is a patterned electric stimulation applied to the skin through surface electrodes, improves two-point discrimination, somatosensory temporal discrimination threshold (STDT) and motor performance in humans. However, the mechanisms which underlie these changes are still unknown. In particular, we hypothesize that refinement of inhibition might be responsible for the improvement in spatial and temporal perception. Fifteen healthy subjects underwent 45min of HF-RSS. Before and after the intervention several measures of inhibition in the primary somatosensory area (S1), such as paired-pulse somatosensory evoked potentials (pp-SEP), high-frequency oscillations (HFO), and STDT were tested, as well as tactile spatial acuity and short intracortical inhibition (SICI). HF-RSS increased inhibition in S1 tested by pp-SEP and HFO; these changes were correlated with improvement in STDT. HF-RSS also enhanced bumps detection, while there was no change in grating orientation test. Finally there was an increase in SICI, suggesting widespread changes in cortical sensorimotor interactions. These findings suggest that HF-RSS can improve spatial and temporal tactile abilities by increasing the effectiveness of inhibitory interactions in the somatosensory system. Moreover, HF-RSS induces changes in cortical sensorimotor interaction. HF-RSS is a repetitive electric stimulation technique able to modify the effectiveness of inhibitory circuitry in the somatosensory system and primary motor cortex. Copyright © 2017 International Federation of Clinical Neurophysiology. All rights reserved.

  7. Increased plasma corticosterone levels after periaqueductal gray stimulation-induced escape reaction or panic attacks in rats.

    Science.gov (United States)

    Lim, Lee Wei; Blokland, Arjan; van Duinen, Marlies; Visser-Vandewalle, Veerle; Tan, Sonny; Vlamings, Rinske; Janssen, Mark; Jahanshahi, Ali; Aziz-Mohammadi, Mujzgan; Steinbusch, Harry W M; Schruers, Koen; Temel, Yasin

    2011-04-15

    The hypothalamo-pituitary-adrenal (HPA) axis is involved in stress, depression and anxiety. Controversy exists on HPA axis activation during panic attacks (PAs). We examined whether the HPA axis is involved in the escape or panic-like response in an animal model of PAs induced by electrical stimulation of the dorsolateral periaqueductal gray (dlPAG) in rats. Additionally, rats were also treated with chronic administration of buspirone (BUSP) and escitalopram (ESCIT), respectively; and they were stimulated in the open-field arena for panic-like reaction. Levels of stress hormone corticosterone were measured following 30 min after escape or panic condition. Our results demonstrated that the levels of plasma corticosterone were significantly increased after the induction of escape or panic-like response in comparison with the sham animals. The levels of corticosterone were significantly decreased in the dlPAG stimulated groups after rats were treated chronically with the ESCIT but not the BUSP as compared to the saline treated animals. Importantly, the increase of corticosterone level after escape or panic-like response was paralleled by an increase of neuronal activation of c-Fos in both the parvocellular and magnocellular paraventricular nucleus of the hypothalamus. Moreover, the c-Fos data also showed a decrease in the number of positive cells particularly for the ESCIT as well as the BUSP in comparison with the saline stimulated animals. In conclusion, the present study clearly demonstrated that PA or escape response activates the HPA axis and it remains difficult to anticipate the mechanism underlying HPA axis during PAs and its relationship with 5-HT drugs. Copyright © 2010 Elsevier B.V. All rights reserved.

  8. Ablation of plasma membrane Ca(2+)-ATPase isoform 4 prevents development of hypertrophy in a model of hypertrophic cardiomyopathy.

    Science.gov (United States)

    Prasad, Vikram; Lorenz, John N; Lasko, Valerie M; Nieman, Michelle L; Jiang, Min; Gao, Xu; Rubinstein, Jack; Wieczorek, David F; Shull, Gary E

    2014-12-01

    The mechanisms linking the expression of sarcomeric mutant proteins to the development of pathological hypertrophy in hypertrophic cardiomyopathy (HCM) remain poorly understood. We investigated the role of the plasma membrane Ca(2+)-ATPase PMCA4 in the HCM phenotype using a transgenic model that expresses mutant (Glu180Gly) α-tropomyosin (Tm180) in heart. Immunoblot analysis revealed that cardiac PMCA4 expression was upregulated early in Tm180 disease pathogenesis. This was accompanied by an increase in levels of the L-type Ca(2+)-channel, which is implicated in pathological hypertrophy. When Tm180 mice were crossed with a PMCA4-null line, loss of PMCA4 caused the abrogation of hypertrophy in Tm180/PMCA4-null double mutant mice. RT-PCR analysis of Tm180/PMCA4-null hearts revealed blunting of the fetal program and reversion of pro-fibrotic Col1a1 and Col3a1 gene expression to wild-type levels. This was accompanied by evidence of reduced L-type Ca(2+)-channel expression, and diminished calcineurin activity. Expression of the metabolic substrate transporters glucose transporter 4 and carnitine palmitoyltransferase 1b was preserved and Tm180-related changes in mRNA levels of various contractile stress-related proteins including the cardiac ankyrin protein CARP and the N2B isoform of titin were reversed in Tm180/PMCA4-null hearts. cGMP levels were increased and phosphorylation of vasodilator-stimulated phosphoprotein was elevated in Tm180/PMCA4-null hearts. These changes were associated with a sharp reduction in left ventricular end-diastolic pressure in Tm180/PMCA4-null hearts, which occurred despite persistence of Tm180-related impairment of relaxation dynamics. These results reveal a novel and specific role for PMCA4 in the Tm180 hypertrophic phenotype, with the "protective" effects of PMCA4 deficiency encompassing multiple determinants of HCM-related hypertrophy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. ErythropoieSIS stimulating agent (ESA use is increased following missed dialysis sessions

    Directory of Open Access Journals (Sweden)

    T. Christopher Bond

    2012-06-01

    Missed session episodes result in significant increases in ESA utilization in the post-miss period, and also in total monthly ESA use. Such increases should be considered in any assessment of impact of missed sessions: both clinical and economic.

  10. Prior AICAR stimulation increases insulin sensitivity in mouse skeletal muscle in an AMPK-dependent manner

    DEFF Research Database (Denmark)

    Kjøbsted, Rasmus; Treebak, Jonas Thue; Fentz, Joachim

    2015-01-01

    Acute exercise increases glucose uptake in skeletal muscle by an insulin-independent mechanism. In the period after exercise insulin sensitivity to increase glucose uptake is enhanced. The molecular mechanisms underpinning this phenomenon are poorly understood, but appear to involve an increased ...

  11. Hyperthermic stimulation of blood increases the immunological effects of granulocyte and monocyte adsorption in vitro: relevance to extracorporeal immunomodulation.

    Science.gov (United States)

    Tozawa, Katsuyuki; Fukunaga, Ken; Kamikozuru, Koji; Ohnishi, Kunio; Hida, Nobuyuki; Ohda, Yoshio; Kusaka, Takeshi; Yoshida, Koji; Jinno, Yoshio; Nagase, Kazuko; Nakamura, Shirou; Miwa, Hiroto; Matsumoto, Takayuki

    2008-10-01

    Extracorporeal granulocyte and monocyte/macrophage adsorption (GMA) using an adacolumn filled with cellulose acetate beads as GMA carriers selectively depletes excess and activated myeloid leucocytes from the circulation and has been used as a non-pharmacologic adjunct therapy in patients with inflammatory bowel disease (IBD). In this study we applied hyperthermic stimulation of blood during exposure to the GMA carriers with the aim of enhancing the release of anti-inflammatory substances from leucocytes. In blood from patients with Crohn's disease (CD) and healthy controls (HC), incubation with the carriers was associated with a striking increase in the release of interleukin-1 receptor antagonist (IL-1ra, a powerful anti-inflammatory cytokine) independent of hyperthermic stimulation, while in the blood from both CD and HC, the release of heat shock protein70 (Hsp70, a cytoprotective protein) was increased by two fold. The present data indicate that hyperthermic stimulation of blood at 43 degrees C or exposure to cellulose acetate carriers is a simple strategy to generate substances of therapeutic potential from blood, especially in patients with IBD. These observations are very interesting in the context of extracorporeal immunomodulation in patients with immune pathology.

  12. Stimulating music increases motor coordination in patients afflicted with Morbus Parkinson.

    Science.gov (United States)

    Bernatzky, Günther; Bernatzky, Patrick; Hesse, Horst-Peter; Staffen, Wolfgang; Ladurner, Gunther

    2004-05-06

    The present study measured the short-term effect of special stimulating music on motor coordination in Parkinson patients. Eleven patients with a dominant akinetic Parkinson syndrome as well as ten healthy persons (age-matched control group) participated in this study. In the Parkinson group, the measurement of fine motor coordination with the 'Vienna Test System' showed an improvement in two (aiming, line tracking) of the four subtests after listening to the music. The patients improved their performance with the right arm significantly in the subtest aiming-error-time. No statistical differences were found in the other two subtests (steadiness, tapping) in both groups. There was also no improvement in frequency of tapping movement on the power-force-working-plate. Accordingly, music effects more the precision of a movement than the speediness. The measurements on the power-force-working-plate showed a significant improvement in two of five measured parameters: contact time, variability coefficient for total step and impact maximum changed significantly. This study gives evidence that specific music can improve the precision of arm and finger movements.

  13. Extensive hypertrophic lupus erythematosus: Atypical presentation

    Directory of Open Access Journals (Sweden)

    Tarun Narang

    2012-01-01

    Full Text Available Lupus erythematosus (LE is a disease with a wide spectrum of cutaneous and systemic manifestations. Clinical features of patients with LE show a great variation, and for this reason it is difficult to develop a unifying concept of this disease. Our objective is to present a case of hypertrophic LE with atypical morphology and extensive involvement, who responded favorably to isotretinoin. Diagnosis of hypertrophic lupus erythematosus (HLE was confirmed by characteristic histopathological findings. Combination therapy with isotretinoin and hydroxychloroquine resulted in flattening and repression of previously refractory skin lesions. Sometimes, HLE lesions may present a diagnostic and therapeutic dilemma. In long standing lesions, squamous cell carcinoma may arise. Therefore, HLE requires adequate therapy with clinical and histopathological follow up.

  14. Increased daylength stimulates plasma growth hormone and gill Na+, K+ and -ATPase Atlantic salmon (Salmo salar )

    Science.gov (United States)

    McCormick, S.D.; Bjornsson, Bjorn Thrandur; Sheridan, M.; Eilertson, C.; Carey, J.B.; O'Dea, M.

    1995-01-01

    Atlantic salmon juveniles reared at constant temperature (9–10°C) were exposed to four photoperiod treatment and sampled every 2 weeks from January through May. Fish reared under normal photoperiod exhibited eight-and three fold increases in plasma growth hormone and gill Na+, K+-ATPase activity, respectively, between January and April. Fish exposed to abrupt increases in daylength (LD 15:9) in February or March responded with earlier increases in plasma growth hormone and gill Na+, K+-ATPase activity, and earlier decreases in condition factor relative to fish in the normal photoperiod group. Fish maintained under short daylength (LD 9:15) from January to May exhibited delayed and muted increases in plasma growth hormone and gill Na+, K+-ATPase activity. Plasma thyroxine exhibited a 2.5-fold increase from February to late March in the normal photoperiod group, was generally lower in the LD 9:15 group, but exhibited no obvious response to abrupt increases in daylength. There was an increase in plasma 3,5,3′-triiodo-l-thyronine with time in all groups (43–80%) but no significant response to photoperiod. Plasma levels of somatostatin-25 were highest in the LD 9:15 group, but there was no detectable response to increased daylength in any of the photoperiod treatments. The results indicate that plasma growth hormone is responsive to increased daylength and may be causally related to subsequent increases in gill Na+, K+-ATPase.

  15. Hypertrophic cardiomyopathy: Part 1 - Introduction, pathology and pathophysiology

    OpenAIRE

    Praveen Kerala Varma; Praveen Kumar Neema

    2014-01-01

    Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disease with many genotype and phenotype variations. Earlier terminologies, hypertrophic obstructive cardiomyopathy and idiopathic hypertrophic sub-aortic stenosis are no longer used to describe this entity. Patients present with or without left ventricular outflow tract (LVOT) obstruction. Resting or provocative LVOT obstruction occurs in 70% of patients and is the most common cause of heart failure. The pathology an...

  16. An increase in renal dopamine does not stimulate natriuresis after fava bean ingestion123

    OpenAIRE

    Garland, Emily M; Cesar, Tericka S; Lonce, Suzanna; Ferguson, Marcus C; Robertson, David

    2013-01-01

    Background: Fava beans (Vicia faba) contain dihydroxyphenylalanine (dopa), and their ingestion may increase dopamine stores. Renal dopamine regulates blood pressure and blood volume via a natriuretic effect.

  17. Magnetic resonance imaging of hypertrophic olivary degeneration.

    Science.gov (United States)

    Blanco Ulla, M; López Carballeira, A; Pumar Cebreiro, J M

    2015-01-01

    To review the pathophysiologic mechanisms involved in hypertrophic olivary degeneration, with attention to epidemiologic and clinical aspects and especially to imaging findings. We reviewed 5 patients diagnosed with hypertrophic olivary degeneration at our center from 2010 through 2013, analyzing relevant clinical, epidemiologic, and radiologic findings. In all cases, a hyperintensity was seen in the inferior olivary nuclei in FLAIR and T2-weighted sequences. No signal alterations were seen on T1-weighted sequences, and no enhancement was seen after intravenous injection of contrast material. In the cases studied by diffusion-weighted imaging, no significant alterations were seen in these sequences. Olivary hypertrophy was seen in all patients except in one, in whom presumably not enough time had elapsed for hypertrophy to occur. The alterations were bilateral in two of the five cases. Only one case exhibited the typical clinical manifestations. Given that patients may not present clinical manifestations that can be attributed to hypertrophic olivary degeneration, it is important to recognize the characteristic radiologic signs of this entity. Copyright © 2014 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

  18. Outcomes of acute myocardial infarction in patients with hypertrophic cardiomyopathy.

    Science.gov (United States)

    Gupta, Tanush; Harikrishnan, Prakash; Kolte, Dhaval; Khera, Sahil; Aronow, Wilbert S; Mujib, Marjan; Palaniswamy, Chandrasekar; Sule, Sachin; Jain, Diwakar; Ahmed, Ali; Lanier, Gregg M; Cooper, Howard A; Frishman, William H; Fonarow, Gregg C; Panza, Julio A

    2015-08-01

    Acute myocardial infarction is a recognized complication in patients with hypertrophic cardiomyopathy. However, limited data are available on outcomes of patients with hypertrophic cardiomyopathy and acute myocardial infarction. We analyzed the 2003-2011 Nationwide Inpatient Sample databases to identify all patients aged ≥18 years with a principal diagnosis of acute myocardial infarction. Patients with a concomitant diagnosis of hypertrophic cardiomyopathy were then identified and analyzed as a separate cohort. Multivariate logistic regression was used to compare outcomes in patients with acute myocardial infarction with and without hypertrophic cardiomyopathy. Of 5,901,827 patients with acute myocardial infarction, 5688 (0.1%) had a diagnosis of hypertrophic cardiomyopathy. Patients with hypertrophic cardiomyopathy were older, more likely to be female, and less likely to have traditional cardiovascular risk factors. Compared with patients without hypertrophic cardiomyopathy, patients with hypertrophic cardiomyopathy were less likely to present with ST-elevation myocardial infarction and more likely to present with non-ST-elevation myocardial infarction. Patients with hypertrophic cardiomyopathy with ST-elevation myocardial infarction or non-ST-elevation myocardial infarction were less likely to receive revascularization. In the overall population with acute myocardial infarction, there was no difference in risk-adjusted in-hospital mortality between patients with and without hypertrophic cardiomyopathy (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.84-1.11; P = .59). In the population with ST-elevation myocardial infarction, patients with hypertrophic cardiomyopathy had lower risk-adjusted in-hospital mortality than those without hypertrophic cardiomyopathy (OR, 0.75; 95% CI, 0.63-0.91; P = .003), whereas in the population with non-ST-elevation myocardial infarction, there was no difference in risk-adjusted in-hospital mortality between patients with

  19. Anodal Stimulation of the Left DLPFC Increases IGT Scores and Decreases Delay Discounting Rate in Healthy Males

    Directory of Open Access Journals (Sweden)

    Qinghua He

    2016-09-01

    Full Text Available Previous correlational imaging studies have implicated the dorsolateral prefrontal cortex (DLPFC in decision making. Using High-Definition Transcranial Direct Current Stimulation (HD-tDCS, the present study directly investigated the causal role of the DLPFC in performing the Iowa Gambling Task (IGT and the Inter-Temporal Choice (ITC task. Three experiments were conducted: Exp. 1 (N = 41 to study the left DLPFC, Exp. 2 (N = 49 to study the right DLPFC, and Exp. 3 (N = 20, a subset of those in Exp. 1 to switch the experimental and control conditions. All participants were healthy male college students. For Exps. 1 and 2, participants were randomly assigned to either the HD- tDCS or the sham stimulation condition. For Exp. 3, participants were assigned to the condition they were not in during Exp. 1. Results showed that HD-tDCS over the left DLPFC increased IGT score, decreased the recency parameter in IGT, and lowered delay discounting rate (k in the ITC task. We discussed the potential roles of impulse control and time perception in mediating the effect of tDCS stimulation of left DLPFC on decision making. Our results have clinical implications for the treatment of disorders involving poor decision-making, such as addictions.

  20. Sucralose Increases Antimicrobial Resistance and Stimulates Recovery of Escherichia coli Mutants.

    Science.gov (United States)

    Qu, Yilin; Li, Rongyan; Jiang, Mingshan; Wang, Xiuhong

    2017-07-01

    Because of heavy use of antimicrobials, antimicrobial resistance in bacteria has become of great concern. The effect of some widely used food additives such as sucralose on bacteria in the gut and the environment has also drawn increasing attention. In this study, we investigated the interaction between antimicrobials and sucralose impacting antimicrobial resistance and mutation of Escherichia coli (E. coli). To examine antimicrobial resistance and mutation frequency, different subinhibitory concentrations of sucralose were added to cultures of E.coli BW25113 that were then treated with antimicrobials, oxolinic acid, or moxifloxacin. Then the E.coli were assayed for bacterial survival and recovery of mutants resistant to an unrelated antimicrobial, rifampicin. Pre-treatment of E.coli BW25113 with 1/2 minimal inhibitory concentration (MIC) of sucralose increased the survival rate in oxolinic acid or moxifloxacin. A 1/3 MIC of sucralose increased rifampicin-resistant mutation rate of E.coli BW25113 after 72 h, while rifampicin-resistant mutation rate was increased when co-treated with 1/8 MIC, 1/4 MIC, 1/3 MIC sucralose, and oxolinic acid after 24 h. Sucralose can increase the antimicrobial resistance and mutation frequency of E.coli to some antimicrobials.

  1. Clinical efficacy of utilizing Ultrapulse CO2 combined with fractional CO2 laser for the treatment of hypertrophic scars in Asians-A prospective clinical evaluation.

    Science.gov (United States)

    Lei, Ying; Li, Shi Feng; Yu, Yi Ling; Tan, Jun; Gold, Michael H

    2017-06-01

    Hypertrophic scarring is seen regularly. Tissue penetration of laser energy into hypertrophic scars using computer defaults from some lasers may be insufficient and penetration not enough. We have developed a treatment with an interrupted laser "drilling" by the Ultrapulse CO2 (Manual Fractional Technology, MFT) and, a second pass, with fractional CO2 . The MFT with fractional CO2 lasers to treat hypertrophic scars is evaluated. A total of 158 patients with hypertrophic scars had three sessions of MFT with fractional CO2 laser at 3-month intervals. Evaluations made before and 6 months after the 3rd treatment: (1) the Vancouver Scar Scale (VSS), (2) the University of North Carolina (UNC) Scar Scale, and (3) a survey of patient satisfaction. All data were analyzed using a t-test before and after treatment. The VSS score decreased from 9.35 to 3.12 (PCO2 laser had profound effects on the hypertrophic scars treated. It works by increasing the penetration depth of the CO2 laser in the scar tissue, exerting more precise effects on the hypertrophic scars. MFT combined with fractional CO2 laser has the potential to be a major advance in the treatment of hypertrophic scars. © 2017 Wiley Periodicals, Inc.

  2. Increasing exposure to antibody-stimulating proteins and polysaccharides in vaccines is not associated with risk of autism.

    Science.gov (United States)

    DeStefano, Frank; Price, Cristofer S; Weintraub, Eric S

    2013-08-01

    To evaluate the association between autism and the level of immunologic stimulation received from vaccines administered during the first 2 years of life. We analyzed data from a case-control study conducted in 3 managed care organizations (MCOs) of 256 children with autism spectrum disorder (ASD) and 752 control children matched on birth year, sex, and MCO. In addition to the broader category of ASD, we also evaluated autistic disorder and ASD with regression. ASD diagnoses were validated through standardized in-person evaluations. Exposure to total antibody-stimulating proteins and polysaccharides from vaccines was determined by summing the antigen content of each vaccine received, as obtained from immunization registries and medical records. Potential confounding factors were ascertained from parent interviews and medical charts. Conditional logistic regression was used to assess associations between ASD outcomes and exposure to antigens in selected time periods. The aOR (95% CI) of ASD associated with each 25-unit increase in total antigen exposure was 0.999 (0.994-1.003) for cumulative exposure to age 3 months, 0.999 (0.997-1.001) for cumulative exposure to age 7 months, and 0.999 (0.998-1.001) for cumulative exposure to age 2 years. Similarly, no increased risk was found for autistic disorder or ASD with regression. In this study of MCO members, increasing exposure to antibody-stimulating proteins and polysaccharides in vaccines during the first 2 years of life was not related to the risk of developing an ASD. Copyright © 2013 Mosby, Inc. All rights reserved.

  3. Altering the architecture of tissue engineered hypertrophic cartilaginous grafts facilitates vascularisation and accelerates mineralisation.

    Directory of Open Access Journals (Sweden)

    Eamon J Sheehy

    Full Text Available Cartilaginous tissues engineered using mesenchymal stem cells (MSCs can be leveraged to generate bone in vivo by executing an endochondral program, leading to increased interest in the use of such hypertrophic grafts for the regeneration of osseous defects. During normal skeletogenesis, canals within the developing hypertrophic cartilage play a key role in facilitating endochondral ossification. Inspired by this developmental feature, the objective of this study was to promote endochondral ossification of an engineered cartilaginous construct through modification of scaffold architecture. Our hypothesis was that the introduction of channels into MSC-seeded hydrogels would firstly facilitate the in vitro development of scaled-up hypertrophic cartilaginous tissues, and secondly would accelerate vascularisation and mineralisation of the graft in vivo. MSCs were encapsulated into hydrogels containing either an array of micro-channels, or into non-channelled 'solid' controls, and maintained in culture conditions known to promote a hypertrophic cartilaginous phenotype. Solid constructs accumulated significantly more sGAG and collagen in vitro, while channelled constructs accumulated significantly more calcium. In vivo, the channels acted as conduits for vascularisation and accelerated mineralisation of the engineered graft. Cartilaginous tissue within the channels underwent endochondral ossification, producing lamellar bone surrounding a hematopoietic marrow component. This study highlights the potential of utilising engineering methodologies, inspired by developmental skeletal processes, in order to enhance endochondral bone regeneration strategies.

  4. Heterogeneity of myocardial fluoro-18 2-deoxyglucose uptake in patients with apical hypertrophic cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Shiba, Nobuyuki; Kagaya, Yutaka; Ishide, Nobumasa [Tohoku Univ., Sendai (Japan). School of Medicine] [and others

    1997-03-01

    We have shown that myocardial glucose metabolism is heterogeneous in patients with hypertrophic cardiomyopathy. It is not known, however, whether glucose metabolism is impaired in patients with apical hypertrophic cardiomyopathy, which is fairly common in Japan. We studied 7 patients with apical hypertrophic cardiomyopathy and 5 normal subjects using fluoro-18 2-deoxyglucose (FDG) and positron emission tomography (PET). We calculated regional FDG fractional uptake and the inter-regional coefficient of variation (CV) of FDG fractional uptake in the interventricular septal, anteroapical, and posterolateral regions. The regional FDG fractional uptake was similar in the 2 groups and among the 3 different segments within each group. However, the inter-regional CV of FDG fractional uptake was increased in the anteroapical wall segment of the patient group compared with the control group and also with the other 2 regions in the patient group. The results did not differ when we studied another 5 patients and 6 normal control subjects with a PET scanner with higher spatial resolution. These data suggest that myocardial glucose metabolism may be impaired in the anteroapical wall segment of patients with apical hypertrophic cardiomyopathy. (author)

  5. Observational retrospective study evaluating the effects of oral isotretinoin in keloids and hypertrophic scars.

    Science.gov (United States)

    Guadanhim, Lilia R S; Gonçalves, Rubens G; Bagatin, Ediléia

    2016-11-01

    Acne vulgaris is a chronic inflammatory disease characterized by non-inflammatory and inflammatory lesions that can cause scarring. Oral isotretinoin is the current recommended treatment for moderate and severe cases; however, there are reports of possible influences on the healing process of the skin, leading to an increase in the risk for hypertrophic scars and keloids. This hypothesis, although unproven, represents a contraindication to the treatment of acne scars during the 6-12 months after the cessation of isotretinoin. The aim of this study was to investigate the prevalences of hypertrophic scars and keloids in acne patients treated with oral isotretinoin. Three data collection strategies were used: (i) clinical examination of patients with acne vulgaris, exposed or unexposed to oral isotretinoin, focusing on the occurrence of hypertrophic scars and/or keloids; (ii) telephone interviews of patients using oral isotretinoin to treat acne vulgaris on the occurrence or worsening of keloids; and (iii) clinical examination of patients with previous use of oral isotretinoin followed at a specific keloid treatment clinic. The resulting data showed no differences in wound healing. These findings may indicate that the occurrence of hypertrophic scars or keloids in patients using oral isotretinoin is an undesirable event arising from an individual response and may be related to inflammatory acne evolution. © 2016 The International Society of Dermatology.

  6. Altering the architecture of tissue engineered hypertrophic cartilaginous grafts facilitates vascularisation and accelerates mineralisation.

    Science.gov (United States)

    Sheehy, Eamon J; Vinardell, Tatiana; Toner, Mary E; Buckley, Conor T; Kelly, Daniel J

    2014-01-01

    Cartilaginous tissues engineered using mesenchymal stem cells (MSCs) can be leveraged to generate bone in vivo by executing an endochondral program, leading to increased interest in the use of such hypertrophic grafts for the regeneration of osseous defects. During normal skeletogenesis, canals within the developing hypertrophic cartilage play a key role in facilitating endochondral ossification. Inspired by this developmental feature, the objective of this study was to promote endochondral ossification of an engineered cartilaginous construct through modification of scaffold architecture. Our hypothesis was that the introduction of channels into MSC-seeded hydrogels would firstly facilitate the in vitro development of scaled-up hypertrophic cartilaginous tissues, and secondly would accelerate vascularisation and mineralisation of the graft in vivo. MSCs were encapsulated into hydrogels containing either an array of micro-channels, or into non-channelled 'solid' controls, and maintained in culture conditions known to promote a hypertrophic cartilaginous phenotype. Solid constructs accumulated significantly more sGAG and collagen in vitro, while channelled constructs accumulated significantly more calcium. In vivo, the channels acted as conduits for vascularisation and accelerated mineralisation of the engineered graft. Cartilaginous tissue within the channels underwent endochondral ossification, producing lamellar bone surrounding a hematopoietic marrow component. This study highlights the potential of utilising engineering methodologies, inspired by developmental skeletal processes, in order to enhance endochondral bone regeneration strategies.

  7. Growth Hormone Is Secreted by Normal Breast Epithelium upon Progesterone Stimulation and Increases Proliferation of Stem/Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Sara Lombardi

    2014-06-01

    Full Text Available Using in vitro and in vivo experimental systems and in situ analysis, we show that growth hormone (GH is secreted locally by normal human mammary epithelial cells upon progesterone stimulation. GH increases proliferation of a subset of cells that express growth hormone receptor (GHR and have functional properties of stem and early progenitor cells. In 72% of ductal carcinoma in situ lesions, an expansion of the cell population that expresses GHR was observed, suggesting that GH signaling may contribute to breast cancer development.

  8. Direct Measurements of an increased threshold for stimulated Brillouin scattering with polarization smoothing in ignition hohlraum plasmas

    Energy Technology Data Exchange (ETDEWEB)

    Froula, D; Divol, L; Berger, R L; London, R; Meezan, N; Neumayer, P; Ross, J S; Stagnito, S; Suter, L; Glenzer, S H; Strozzi, D

    2007-11-08

    We demonstrate a significant reduction of stimulated Brillouin scattering by polarization smoothing. The intensity threshold is measured to increase by a factor of 1.7 {+-} 0.2 when polarization smoothing is applied. The results were obtained in a high-temperature (T{sub 3} {approx_equal} 3 keV) hohlraum plasma where filamentation is negligible in determining the backscatter threshold. These results are explained by an analytical model relevant to ICF plasma conditions that modifies the linear gain exponent to account for polarization smoothing.

  9. Wounding stimulates ALLENE OXIDE SYNTHASE gene and increases the level of jasmonic acid in Ipomoea nil cotyledons

    Directory of Open Access Journals (Sweden)

    Emilia Wilmowicz

    2016-03-01

    Full Text Available Allene oxide synthase (AOS encodes the first enzyme in the lipoxygenase pathway, which is responsible for jasmonic acid (JA formation. In this study we report the molecular cloning and characterization of InAOS from Ipomoea nil. The full-length gene is composed of 1662 bp and encodes for 519 amino acids. The predicted InAOS contains PLN02648 motif, which is evolutionarily conserved and characteristic for functional enzymatic proteins. We have shown that wounding led to a strong stimulation of the examined gene activity in cotyledons and an increase in JA level, which suggest that this compound may be a modulator of stress responses in I. nil.

  10. Regularity increases middle latency evoked and late induced beta brain response following proprioceptive stimulation

    DEFF Research Database (Denmark)

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

    2008-01-01

    as an indication of increased readiness. This is achieved through detailed analysis of both evoked and induced responses in the time-frequency domain. Electroencephalography in a 64 channels montage was recorded in four-teen healthy subjects. Two paradigms were explored: A Regular alternation between hand...

  11. Increased yield pressure in the anal canal during sacral nerve stimulation: a pilot study with the functional lumen imaging probe.

    Science.gov (United States)

    Haas, S; Liao, D; Gregersen, H; Lundby, L; Laurberg, S; Krogh, K

    2017-02-01

    Sacral nerve stimulation (SNS) is a well-established treatment for fecal incontinence but its mode of action remains obscure. Anal sphincter function is usually evaluated with manometry but resistance to distension may be a more appropriate parameter than luminal pressure. The functional lumen imaging probe allows detailed description of distension properties of the anal canal. Our objective in this study was to characterize the impact of SNS on distension properties of the anal canal in patients with idiopathic fecal incontinence. We studied 10 women (median age 64 [44-79] years) with idiopathic fecal incontinence at baseline and during SNS. The luminal geometry of the anal canal was examined with the FLIP at rest and during squeeze and the distensibility of the anal canal was investigated during filling of the bag. All patients were successfully treated with SNS and the mean Wexner Incontinence Score was reduced from 14.9 ± 4 to 7.1 ± 4.8 (Panal canal during distension (yield pressure) increased from 14.5 ± 12.2 mmHg at baseline to 20.5 ± 13.3 mmHg during SNS (Panal canal. The yield pressure and the resistance to distension increased in response to SNS for idiopathic fecal incontinence. This will inevitably increase the resistance to flow through the anal canal, which may contribute to the benefits of sacral nerve stimulation. © 2016 John Wiley & Sons Ltd.

  12. Caffeine stimulates voluntary wheel running in mice without increasing aerobic capacity.

    Science.gov (United States)

    Claghorn, Gerald C; Thompson, Zoe; Wi, Kristianna; Van, Lindsay; Garland, Theodore

    2017-03-01

    The "energy drink" Red Bull and the "sports drink" Gatorade are often marketed to athletes, with claims that they cause performance gains. However, both are high in sugars, and also consumed by non-athletes. Few studies have addressed the effects of these drinks or their biologically active components in rodent exercise models. We used three experiments to test effects on both voluntary exercise behavior and maximal aerobic capacity in lines of mice known to differ in "athletic" traits. Mice from four replicate High Runner (HR) lines have been selectively bred for voluntary running on wheels, and run approximately three times as many revolutions per day as do mice from four non-selected Control (C) lines. HR mice also have higher endurance and maximal oxygen consumption (VO 2 max) during forced treadmill exercise. In Experiment 1, we tested the hypothesis that Gatorade or Red Bull might cause or allow mice to increase their voluntary wheel running. On days 5 and 6 of 6days of wheel access, as is used to select breeders, HR mice ran 3.3-fold more than C, and females ran 1.2-fold more than males, with no linetype by sex interaction. On day 7, mice were administered Gatorade, Red Bull or tap water. During the subsequent 19-hour period, Gatorade had no statistical effect on running, but Red Bull significantly increased distance run by both sexes and in both HR and C lines. The increase in distance run caused by Red Bull was attributable to time spent running, not an increase in mean (or maximum) speed. As previous studies have found that sucrose alone does not generally increase wheel running, we tested two other active ingredients in Red Bull, caffeine and taurine, in Experiment 2. With a similar testing protocol, caffeine alone and caffeine+taurine increased running by about half the magnitude of Red Bull. In Experiment 3, we tested the hypothesis that Red Bull or caffeine alone can increase physiological performance ability during aerobic exercise, measured as VO 2

  13. Peroxynitrate formed during a transient episode of brain ischemia increases endothelium-derived hyperpolarization-type dilations in thromboxane/prostaglandin receptor stimulated rat cerebral arteries

    OpenAIRE

    Onetti, Yara; Dantas, Ana Y.; Perez, Belen; McNeish, Alister J.; Vila, Elisabet; Jimenez-Altyayo, Francesc

    2017-01-01

    Aim\\ud Increased thromboxane A2 and peroxynitrite are hallmarks of cerebral ischemia/reperfusion (I/R). Stimulation of thromboxane/prostaglandin receptors (TP) attenuates endothelium-derived hyperpolarization (EDH). We investigated whether EDH-type middle cerebral artery (MCA) relaxations following TP stimulation are altered after I/R and the influence of peroxynitrite.\\ud \\ud Methods\\ud Vascular function was determined by wire myography after TP stimulation with the thromboxane A2 mimetic 9,...

  14. Increasing digesta viscosity using carboxymethylcellulose in weaned piglets stimulates ileal goblet cell numbers and maturation.

    Science.gov (United States)

    Piel, Christelle; Montagne, Lucile; Sève, Bernard; Lallès, Jean-Paul

    2005-01-01

    Intestinal mucin, a family of glycoproteins secreted by goblet cells, is the main constituent of the mucus protecting the gastrointestinal tract. For optimal mucosal protection, both the quantitative and qualitative characteristics of mucin are essential. To evaluate how viscosity influences ileal apparent digestibility and mucin biology, a highly viscous nonfermentable soluble polysaccharide, carboxymethylcellulose (CMC), was fed to weaned piglets for 15 d. The ileal crude mucin concentration was determined by ethanol precipitation, and changes in goblet cell subtypes were analyzed by the histochemistry of ileal and colonic tissues. As expected, CMC increased the viscosity of ileal digesta and the moisture of feces (P digestibility of dry matter, organic matter, nitrogen, and minerals. The number of total ileal goblet cells per villus also was higher (+30%, P piglets fed CMC increased the ileal mucin output and numbers and maturation of goblet cells in ileal villi without effects on the apparent digestibility of the diet.

  15. Heme Induction with Delta-Aminolevulinic Acid Stimulates an Increase in Water and Electrolyte Excretion

    Directory of Open Access Journals (Sweden)

    Syed Quadri

    2012-01-01

    Full Text Available Purpose. Studies were performed to examine hemodynamic and renal function before and after acute induction of the endogenous CO system with delta-aminolevulinic acid (DALA, which drives HO activity. Methods. In vivo studies were conducted on Inactin-anesthetized male Sprague Dawley rats (250–300 g either with or without chronic pretreatment with L-NAME (50 mg/Kg, q12 hours x4d. Results. DALA (80 μmol/Kg, IV bolus administration acutely increased endogenous CO production and HO-1 protein. In untreated and L-NAME-pretreated rats, DALA did not alter BP, GFR, or RBF but increased UF, UNaV, and UKV (untreated: Δ108.8 ± 0.28%, 172.1 ± 18.4%, and 165.2 ± 45.9%; pretreated: Δ109.4 ± 0.29%, 187.3 ± 26.9%, and 197.2 ± 45.7%. Acute administration of biliverdin (20 mg/kg, IV and bilirubin (30 mg/kg, IV to similarly treated animals did not alter UF, UNaV, and UKV. Conclusion. These results demonstrate that heme oxygenase induction increases urine and electrolyte excretion and suggest a direct tubular action of endogenous carbon monoxide.

  16. Fenugreek increases insulin-stimulated creatine content in L6C11 muscle myotubes.

    Science.gov (United States)

    Tomcik, Kristyen A; Smiles, William J; Camera, Donny M; Hügel, Helmut M; Hawley, John A; Watts, Rani

    2017-04-01

    Creatine uptake by muscle cells is increased in the presence of insulin. Accordingly, compounds with insulin-like actions may also augment creatine uptake. The aim of this study was to investigate whether Trigonella foenum-graecum (fenugreek), an insulin mimetic, increases total intracellular creatine levels in vitro. Total cellular creatine content was measured fluorometrically in L6C11 muscle myotubes treated for 1, 4, and 24 h with 0.5 mM creatine (CR), CR and 20 μg/mL fenugreek seed extract (CR + FEN), CR and 100 nM insulin (CR + INS), and CR + INS + FEN (n = 6 per treatment group). Alterations in the expression of the sodium- and chloride-dependent creatine transporter, SLC6A8, and key signaling proteins in the PI3-K/Akt pathway were determined. Compared to control (CON), CR + INS + FEN increased total creatine content after 4 h (P  CON and CR at 1 h (P  CON, CR, and CR + INS at 4 h (P creatine content via a mechanism which is independent of the activity of SLC6A8, suggesting that an alternative mechanism is responsible for the regulation and facilitation of insulin-mediated creatine uptake in skeletal muscle cells.

  17. The Increased Expression of Connexin and VEGF in Mouse Ovarian Tissue Vitrification by Follicle Stimulating Hormone

    Directory of Open Access Journals (Sweden)

    Yanzhou Yang

    2015-01-01

    Full Text Available Ovarian follicular damages were caused by cryoinjury during the process of ovarian vitrification and ischemia/reperfusion during the process of ovarian transplantation. And appropriate FSH plays an important role in antiapoptosis during ovarian follicle development. Therefore, in this study, 0.3 IU/mL FSH was administered into medium during mouse ovarian cryopreservation by vitrification to ascertain the function of FSH on ovarian vitrification and avascular transplantation. The results suggested that the expressions of Cx37, Cx43, apoptotic molecular caspase-3, and angiogenesis molecular VEGF were confirmed using immunohistochemistry, western blotting, and real-time PCR, and the results suggested that the treatment with FSH remarkably increased the number of morphologically normal follicles in vitrified/warmed ovaries by upregulating the expression of Cx37, Cx43, VEGF, and VEGF receptor 2, but downregulating the expression of caspase-3. In addition, the vitrified/warmed ovaries were transplanted, and the related fertility was analyzed, and the results suggested that the fertility, neoangiogenesis, and follicle reserve were remarkably increased in the FSH administrated group. Taken together, administration of 0.3 IU/mL FSH during ovarian cryopreservation by vitrification can maintain ovarian survival during ovarian vitrification and increases the blood supply with avascular transplantation via upregulation of Cx43, Cx37, and VEGF/VEGFR2, as well as through its antiapoptotic effects.

  18. Adrenal Demedullation and Oxygen Supplementation Independently Increase Glucose-Stimulated Insulin Concentrations in Fetal Sheep With Intrauterine Growth Restriction

    Science.gov (United States)

    Macko, Antoni R.; Yates, Dustin T.; Chen, Xiaochuan; Shelton, Leslie A.; Kelly, Amy C.; Davis, Melissa A.; Camacho, Leticia E.; Anderson, Miranda J.

    2016-01-01

    In pregnancies complicated by placental insufficiency and intrauterine growth restriction (IUGR), fetal glucose and oxygen concentrations are reduced, whereas plasma norepinephrine and epinephrine concentrations are elevated throughout the final third of gestation. Here we study the effects of chronic hypoxemia and hypercatecholaminemia on β-cell function in fetal sheep with placental insufficiency-induced IUGR that is produced by maternal hyperthermia. IUGR and control fetuses underwent a sham (intact) or bilateral adrenal demedullation (AD) surgical procedure at 0.65 gestation. As expected, AD-IUGR fetuses had lower norepinephrine concentrations than intact-IUGR fetuses despite being hypoxemic and hypoglycemic. Placental insufficiency reduced fetal weights, but the severity of IUGR was less with AD. Although basal plasma insulin concentrations were lower in intact-IUGR and AD-IUGR fetuses compared with intact-controls, glucose-stimulated insulin concentrations were greater in AD-IUGR fetuses compared with intact-IUGR fetuses. Interestingly, AD-controls had lower glucose- and arginine-stimulated insulin concentrations than intact-controls, but AD-IUGR and AD-control insulin responses were not different. To investigate chronic hypoxemia in the IUGR fetus, arterial oxygen tension was increased to normal levels by increasing the maternal inspired oxygen fraction. Oxygenation of IUGR fetuses enhanced glucose-stimulated insulin concentrations 3.3-fold in intact-IUGR and 1.7-fold in AD-IUGR fetuses but did not lower norepinephrine and epinephrine concentrations. Together these findings show that chronic hypoxemia and hypercatecholaminemia have distinct but complementary roles in the suppression of β-cell responsiveness in IUGR fetuses. PMID:26937714

  19. Red yeast rice stimulates osteoblast proliferation and increases alkaline phosphatase activity in MC3T3-E1 cells.

    Science.gov (United States)

    Cho, Young-Eun; Alcantara, Ethel; Kumaran, Santhy; Son, Kun-Ho; Sohn, Ho-Yong; Lee, Jong-Hwa; Choi, Chung-Sig; Ha, Tae-Youl; Kwun, In-Sook

    2010-07-01

    Red yeast (Monascus purpureus) is used as a traditional hypocholesterolemic dietary food component in Asia due to its bioactive component, lovastatin. Recently, new evidence suggesting that the statins in red yeast enhance bone formation has been reported, but more research is still needed in order to support these claims of osteogenic effects. Therefore, in this study, we hypothesized that red yeast rice (in which red yeast is fermented) can improve osteogenic function through osteoblast cell proliferation and differentiation. We studied the effect of methanol extract of red yeast rice powder (RYRP) on osteoblast proliferation and differentiation by measuring mitochondrial enzyme activity and bone marker alkaline phosphatase (ALP) activity, respectively. Osteoblast-like MC3T3-E1 cells were cultured in various concentrations of RYRP methanol extract (0.001-1 mg/mL) during the osteoblast differentiation period (1, 5, 10, and 15 days). As measured by 3-[4,5-dimethylthiazol-2-y]-2,5-diphenyltetrazolium bromide assay, RYRP extracts stimulated cell proliferation during a 24-hour period, compared to cooked white rice powder extract. The most pronounced effect was observed at the concentration range between 0.075 and 0.1 mg/mL. This RYRP stimulatory effect for cell proliferation was observed during the whole osteogenic period. Cellular (synthesized) ALP activity was increased at a RYRP extract concentration of 0.075 mg/mL during 15 days of culture, but the medium (secreted) ALP activity did not show any significant change. This cellular ALP activity stimulation by RYRP extract was confirmed by the staining of ALP activity on cell matrix layers for matrix calcification. The results imply that RYRP extract may increase osteogenic effect by stimulating cell proliferation and ALP activity in osteoblastic cells. Copyright 2010 Elsevier Inc. All rights reserved.

  20. High Thyroid-stimulating Hormone Levels Increase Proinflammatory and Cardiovascular Markers in Patients with Extreme Obesity.

    Science.gov (United States)

    Gómez-Zamudio, Jaime Héctor; Mendoza-Zubieta, Victoria; Ferreira-Hermosillo, Aldo; Molina-Ayala, Marío Antonio; Valladares-Sálgado, Adán; Suárez-Sánchez, Fernando; de Jesús Peralta-Romero, Jose; Cruz, Miguel

    2016-08-01

    Obesity is an important health problem worldwide and many studies have suggested a relationship between obesity and thyroid function, with controversial results. Interestingly, high TSH levels have been involved with the presence of inflammatory state and risk for developing cardiovascular diseases in hypothyroid and obese patients. The aim in this work was to determine the prevalence of hypothyroidism in patients with extreme obesity and to determine whether their TSH levels were related to increased serum levels of inflammatory and cardiovascular markers. A cross-sectional study in 101 patients with extreme obesity (BMI ≥40) was performed. Anthropometric (weight, height and waist circumference) and biochemical (fasting glucose, glycosylated hemoglobin, triglycerides, total cholesterol, LDL-C, HDL-C and insulin) parameters were measured. TSH and FT4 levels as well as clinical exploration for diagnosis of hypothyroidism were carried out. Serum concentration of IL-10, IL-6, adiponectin, resistin, leptin, ICAM-1, VCAM-1 and E-selectin were determined. A high prevalence for diabetes (37.6%), prediabetes (50.5%), dyslipidemia (74.3%), hypertension (61.4%) and hypothyroidism (48.5%) was observed in patients with extreme obesity. The presence of hypothyroidism increased serum concentration of proinflammatory cytokines IL-6 and leptin and decreased the antiinflammatory cytokine adiponectin. In addition, serum TSH levels showed a correlation for waist circumference, weight, BMI, A1c, insulin, IL-6, leptin, ICAM-1 and E-selectin. There is a high prevalence for hypothyroidism in patients with extreme obesity. High levels of TSH contribute to elevate proinflammatory and cardiovascular risk markers, increasing the risk for development of cardiovascular diseases. Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.

  1. Absence of intestinal microbiota increases ß-cyclodextrin stimulated reverse cholesterol transport.

    Science.gov (United States)

    Mistry, Rima H; Verkade, Henkjan J; Tietge, Uwe J F

    2017-05-01

    Non-digestible oligosaccharides are used as prebiotics for perceived health benefits, among these modulating lipid metabolism. However, the mechanisms of action are incompletely understood. The present study characterized the impact of dietary ß-cyclodextrin (ßCD, 10%, w/w), a cyclic oligosaccharide, on sterol metabolism and reverse cholesterol transport (RCT) in conventional and also germ-free mice to establish dependency on metabolism by intestinal bacteria. In conventional ßCD-fed C57BL/6J wild-type mice plasma cholesterol decreased significantly (-40%, p cholesterol levels and biliary cholesterol secretion were unaltered. Changes in cholesterol metabolism translated into increased macrophage-to-feces RCT in ßCD-administered mice (1.5-fold, p cholesterol (-40%, p cholesterol levels and increases fecal cholesterol excretion from a RCT-relevant pool. Intestinal bacteria decrease the impact of ßCD on RCT. These data suggest that dietary ßCD might have cardiovascular health benefits. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Increased secretion of granulocyte-macrophage colony-stimulating factor in mucosal lesions of inflammatory bowel disease.

    Science.gov (United States)

    Noguchi, M; Hiwatashi, N; Liu, Z X; Toyota, T

    2001-01-01

    Granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-3 transmit a same signal needed for growth and activation in granulocytes and macrophages, because these receptors utilize a common beta chain. Little is known about growth factors for intestinal myeloid cells in lesions of inflammatory bowel disease (IBD). To find out whether GM-CSF is produced by the intestinal cells in IBD patients and controls. We measured levels of GM-CSF, tumor necrosis factor (TNF), and IL-3 in the media of organ culture and lamina propria mononuclear cells (LPMCs) culture of colonic mucosa from the patients with IBD. Next, we have investigated GM-CSF production of colonic epithelial cell lines. Spontaneous secretion of GM-CSF was increased in inflamed mucosa, while secretion of IL-3 was not detected. Release of GM-CSF was enhanced in LPMCs from inflamed mucosa. Mucosal GM-CSF production was correlated to TNF-alpha production. Colonic epithelial cell line and T cell produced GM-CSF with superantigen stimulation. We revealed pivotal production of GM-CSF but not IL-3 in intestinal lesion of IBD. Increased secretion of GM-CSF might lead to chronic gut inflammation. Copyright 2001 S. Karger AG, Basel

  3. Keloid and Hypertrophic Scars Are the Result of Chronic Inflammation in the Reticular Dermis

    Directory of Open Access Journals (Sweden)

    Rei Ogawa

    2017-03-01

    Full Text Available Keloids and hypertrophic scars are caused by cutaneous injury and irritation, including trauma, insect bite, burn, surgery, vaccination, skin piercing, acne, folliculitis, chicken pox, and herpes zoster infection. Notably, superficial injuries that do not reach the reticular dermis never cause keloidal and hypertrophic scarring. This suggests that these pathological scars are due to injury to this skin layer and the subsequent aberrant wound healing therein. The latter is characterized by continuous and histologically localized inflammation. As a result, the reticular layer of keloids and hypertrophic scars contains inflammatory cells, increased numbers of fibroblasts, newly formed blood vessels, and collagen deposits. Moreover, proinflammatory factors, such as interleukin (IL-1α, IL-1β, IL-6, and tumor necrosis factor-α are upregulated in keloid tissues, which suggests that, in patients with keloids, proinflammatory genes in the skin are sensitive to trauma. This may promote chronic inflammation, which in turn may cause the invasive growth of keloids. In addition, the upregulation of proinflammatory factors in pathological scars suggests that, rather than being skin tumors, keloids and hypertrophic scars are inflammatory disorders of skin, specifically inflammatory disorders of the reticular dermis. Various external and internal post-wounding stimuli may promote reticular inflammation. The nature of these stimuli most likely shapes the characteristics, quantity, and course of keloids and hypertrophic scars. Specifically, it is likely that the intensity, frequency, and duration of these stimuli determine how quickly the scars appear, the direction and speed of growth, and the intensity of symptoms. These proinflammatory stimuli include a variety of local, systemic, and genetic factors. These observations together suggest that the clinical differences between keloids and hypertrophic scars merely reflect differences in the intensity, frequency

  4. TLR2 Expression Is Increased in Rosacea and Stimulates Enhanced Serine Protease Production by Keratinocytes

    Science.gov (United States)

    Yamasaki, Kenshi; Kanada, Kimberly; Macleod, Daniel T.; Borkowski, Andrew W.; Morizane, Shin; Nakatsuji, Teruaki; Cogen, Anna L.; Gallo, Richard L.

    2011-01-01

    A diverse environment challenges skin to maintain temperature, hydration, and electrolyte balance while also maintaining normal immunological function. Rosacea is a common skin disease that manifests unique inflammatory responses to normal environmental stimuli. We hypothesized that abnormal function of innate immune pattern recognition could explain the enhanced sensitivity of patients with rosacea, and observed that the epidermis of patients with rosacea expressed higher amounts of Toll-like receptor 2 (TLR2) than normal patients. Increased expression of TLR2 was not seen in other inflammatory skin disorders such as atopic dermatitis or psoriasis. Overexpression of TLR2 on keratinocytes, treatment with TLR2 ligands, and analysis of TLR2-deficient mice resulted in a calcium-dependent release of kallikrein 5 from keratinocytes, a critical protease involved in the pathogenesis of rosacea. These observations show that abnormal TLR2 function may explain enhanced inflammatory responses to environmental stimuli and can act as a critical element in the pathogenesis of rosacea. PMID:21107351

  5. Currently known risk factors for hypertrophic skin scarring : A review

    NARCIS (Netherlands)

    Butzelaar, L.; Ulrich, M. M W; Mink Van Der Molen, A. B.; Niessen, F. B.; Beelen, R. H J

    2016-01-01

    SummaryObjective The study aims to provide an overview of risk factors for hypertrophic scarring. Background Hypertrophic skin scarring remains a major concern in medicine and causes considerable morbidity. Despite extensive research on this topic, the precise mechanism of excessive scarring is

  6. Topical modalities for treatment and prevention of postsurgical hypertrophic scars.

    Science.gov (United States)

    Foo, Chong Wee; Tristani-Firouzi, Payam

    2011-08-01

    There is no universally accepted treatment regimen and no evidence-based literature to guide management of hypertrophic scars. This article summarizes the existing literature regarding topical treatments such as silicone gel sheeting and ointment, onion extract, vitamin E, pressure garment therapy, massage therapy, and topical imiquimod 5% cream in the management of hypertrophic scars. 2011 Elsevier Inc. All rights reserved.

  7. The KCNE genes in hypertrophic cardiomyopathy: a candidate gene study

    DEFF Research Database (Denmark)

    Hedley, Paula L; Haundrup, Ole; Andersen, Paal S

    2011-01-01

    as well as the T-tubules of the sarcolemma. It has been suggested that minK forms part of an "electro-mechanical feed-back" which links cardiomyocyte stretching to changes in ion channel function. We examined whether mutations in KCNE genes were associated with hypertrophic cardiomyopathy (HCM), a genetic...... disease associated with an improper hypertrophic response....

  8. Septal alcoholization in hypertrophic cardiomyopathy: about 11 cases

    African Journals Online (AJOL)

    Outcomes of septal alcoholization in hypertrophic obstructive cardiomyopathy are not enough studied in all centers. The purpose of this study was to determine the outcomes of septal alcoholization in hypertrophic obstructive cardiomyopathy in our hospital. A retrospective and prospective descriptive study focused on all ...

  9. Inhibited early immunologic response is associated with hypertrophic scarring

    NARCIS (Netherlands)

    Butzelaar, Liselotte; Schooneman, Dennis P. M.; Soykan, Ezgi A.; Talhout, Wendy; Ulrich, Magda M. W.; van den Broek, Lenie J.; Gibbs, Susan; Beelen, Robert H. J.; van der Molen, Aebele B. Mink; Niessen, Frank B.

    2016-01-01

    This study aimed to examine changes in the inflammatory response in early hypertrophic compared to normal wound healing. The immune system is thought to be involved in hypertrophic scar formation. However, the exact mechanism and time of onset of the derailment remain unknown. In a prospective

  10. Fermentable carbohydrate stimulates FFAR2-dependent colonic PYY cell expansion to increase satiety.

    Science.gov (United States)

    Brooks, Lucy; Viardot, Alexander; Tsakmaki, Anastasia; Stolarczyk, Emilie; Howard, Jane K; Cani, Patrice D; Everard, Amandine; Sleeth, Michelle L; Psichas, Arianna; Anastasovskaj, Jelena; Bell, Jimmy D; Bell-Anderson, Kim; Mackay, Charles R; Ghatei, Mohammad A; Bloom, Stephen R; Frost, Gary; Bewick, Gavin A

    2017-01-01

    Dietary supplementation with fermentable carbohydrate protects against body weight gain. Fermentation by the resident gut microbiota produces short-chain fatty acids, which act at free fatty acid receptor 2 (FFAR2). Our aim was to test the hypothesis that FFAR2 is important in regulating the beneficial effects of fermentable carbohydrate on body weight and to understand the role of gut hormones PYY and GLP-1. Wild-type or Ffar2(-/-) mice were fed an inulin supplemented or control diet. Mice were metabolically characterized and gut hormone concentrations, enteroendocrine cell density measurements were carried out. Intestinal organoids and colonic cultures were utilized to substantiate the in vivo findings. We provide new mechanistic insight into how fermentable carbohydrate regulates metabolism. Using mice that lack FFAR2, we demonstrate that the fermentable carbohydrate inulin acts via this receptor to drive an 87% increase in the density of cells that produce the appetite-suppressing hormone peptide YY (PYY), reduce food intake, and prevent diet-induced obesity. Our results demonstrate that FFAR2 is predominantly involved in regulating the effects of fermentable carbohydrate on metabolism and does so, in part, by enhancing PYY cell density and release. This highlights the potential for targeting enteroendocrine cell differentiation to treat obesity.

  11. Pholcodine stimulates a dramatic increase of IgE in IgE-sensitized individuals. A pilot study.

    Science.gov (United States)

    Florvaag, E; Johansson, S G O; Oman, H; Harboe, T; Nopp, A

    2006-01-01

    A previous study showed a relation between pholcodine (PHO) consumption, prevalence of IgE-sensitization to PHO, morphine (MOR) and suxamethonium (SUX) and anaphylaxis to neuromuscular blocking agents (NMBA). The purpose of this pilot study was to explore the effect on IgE production, in IgE-sensitized and nonsensitized individuals, of exposure to cough syrup and environmental chemicals containing PHO, MOR and SUX related allergenic structures. Serum concentrations of IgE and IgE antibodies to PHO, MOR and SUX allergens measured by ImmunoCAP (Pharmacia Diagnostics, Uppsala, Sweden) were followed after intake of cough syrup, or exposure to confectionary and other household chemicals containing various amounts of substances cross-reacting with PHO, MOR and SUX. Cough syrup containing PHO gave, in sensitized individuals, within 1-2 weeks, an increase of IgE of 60-105 times and of IgE antibodies to PHO, MOR and SUX in the order of 30-80 times. The tested confectionary did not have any similar stimulating effect but seemed to counteract the expected decrease of IgE. No effect was seen in nonsensitized individuals. The PHO stimulated IgE showed a nonspecific binding to ImmunoCAP with common allergens and glycine background ImmunoCAP that was up to 10-fold higher than that of monomeric myeloma-IgE at twice the concentration. It seems as cough syrups containing PHO have a most remarkable IgE boostering effect in persons IgE-sensitized to PHO, MOR and SUX related allergens. Household chemicals containing such allergenic epitopes seem capable of some, minor, stimulation.

  12. Kinematic evidence that atmospheric nitrogen dioxide increases the rates of cell proliferation and enlargement to stimulate leaf expansion in Arabidopsis.

    Science.gov (United States)

    Takahashi, Misa; Morikawa, Hiromichi

    2015-01-01

    To elucidate the stimulation of leaf growth by atmospheric nitrogen dioxide (NO2), we performed a kinematic analysis of the eighth leaves of Arabidopsis thaliana (accession C24) plants grown for 17-35 days after sowing in the presence or absence of 50 ppb NO2 (designated +NO2 plants and -NO2 plants, respectively). We found that the peak and mean values of the relative rates of leaf expansion, cell division and cell expansion were always greater in +NO2 plants than in -NO2 plants. No evidence for prolonged duration was obtained. Thus, NO2 treatment increased the rates of both cell proliferation and enlargement to increase leaf size. Furthermore, a fold-change analysis showed that cell proliferation and enlargement differentially regulated NO2-induced leaf expansion.

  13. Increased heart rate caused by atrial pacing with the closed-loop stimulation function prevented micturition syncope

    Directory of Open Access Journals (Sweden)

    Tatsuo Haraki, MD,PhD

    2013-10-01

    Full Text Available A 70-year-old man had been experiencing syncope several times a year. We implanted a DDD pacemaker with closed-loop stimulation (CLS function. When he urinated early in the morning, his increased atrial pacing rates elevated his heart rate (HR during and after micturition. After implantation of the DDD-CLS mode, he did not experience symptoms. In contrast, in the DDD-R mode, his intrinsic HR changed to atrial pacing after micturition but decreased to the basal rate within 2 min, and he experienced a sense of cold perspiration and presyncope. Increased HRs caused by atrial pacing with the CLS function were useful in the prevention of micturition syncope.

  14. Increased BOLD Signals Elicited by High Gamma Auditory Stimulation of the Left Auditory Cortex in Acute State Schizophrenia

    Directory of Open Access Journals (Sweden)

    Hironori Kuga, M.D.

    2016-10-01

    We acquired BOLD responses elicited by click trains of 20, 30, 40 and 80-Hz frequencies from 15 patients with acute episode schizophrenia (AESZ, 14 symptom-severity-matched patients with non-acute episode schizophrenia (NASZ, and 24 healthy controls (HC, assessed via a standard general linear-model-based analysis. The AESZ group showed significantly increased ASSR-BOLD signals to 80-Hz stimuli in the left auditory cortex compared with the HC and NASZ groups. In addition, enhanced 80-Hz ASSR-BOLD signals were associated with more severe auditory hallucination experiences in AESZ participants. The present results indicate that neural over activation occurs during 80-Hz auditory stimulation of the left auditory cortex in individuals with acute state schizophrenia. Given the possible association between abnormal gamma activity and increased glutamate levels, our data may reflect glutamate toxicity in the auditory cortex in the acute state of schizophrenia, which might lead to progressive changes in the left transverse temporal gyrus.

  15. Dopaminergic stimulation increases selfish behavior in the absence of punishment threat.

    Science.gov (United States)

    Pedroni, Andreas; Eisenegger, Christoph; Hartmann, Matthias N; Fischbacher, Urs; Knoch, Daria

    2014-01-01

    People often face decisions that pit self-interested behavior aimed at maximizing personal reward against normative behavior such as acting cooperatively, which benefits others. The threat of social sanctions for defying the fairness norm prevents people from behaving overly selfish. Thus, normative behavior is influenced by both seeking rewards and avoiding punishment. However, the neurochemical processes mediating the impact of these influences remain unknown. Several lines of evidence link the dopaminergic system to reward and punishment processing, respectively, but this evidence stems from studies in non-social contexts. The present study investigates dopaminergic drug effects on individuals' reward seeking and punishment avoidance in social interaction. Two-hundred one healthy male participants were randomly assigned to receive 300 mg of L-3,4-dihydroxyphenylalanine (L-DOPA) or a placebo before playing an economic bargaining game. This game involved two conditions, one in which unfair behavior could be punished and one in which unfair behavior could not be punished. In the absence of punishment threats, L-DOPA administration led to more selfish behavior, likely mediated through an increase in reward seeking. In contrast, L-DOPA administration had no significant effect on behavior when faced with punishment threats. The results of this study broaden the role of the dopaminergic system in reward seeking to human social interactions. We could show that even a single dose of a dopaminergic drug may bring selfish behavior to the fore, which in turn may shed new light on potential causal relationships between the dopaminergic system and norm abiding behaviors in certain clinical subpopulations.

  16. Triiodothyronine acutely stimulates glucose transport into L6 muscle cells without increasing surface GLUT4, GLUT1, or GLUT3.

    Science.gov (United States)

    Teixeira, Silvania Silva; Tamrakar, Akhilesh K; Goulart-Silva, Francemilson; Serrano-Nascimento, Caroline; Klip, Amira; Nunes, Maria Tereza

    2012-07-01

    Thyroid hormones (THs) act genomically to stimulate glucose transport by elevating glucose transporter (Slc2a) expression and glucose utilization by cells. However, nongenomic effects of THs are now emerging. Here, we assess how triiodothyronine (T(3)) acutely affects glucose transport and the content of GLUT4, GLUT1, and GLUT3 at the surface of muscle cells, and possible interactions between T(3) and insulin action. Differentiated L6 myotubes transfected with myc-tagged Slc2a4 (L6-GLUT4myc) or Slc2a1 (L6-GLUT1myc) and wild-type L6 myotubes were studied in the following conditions: control, hypothyroid (Tx), Tx plus T(3), Tx plus insulin, and Tx plus insulin and T(3). Glucose uptake and GLUT4 content at the cell surface decreased in the Tx group relative to controls. T(3) treatment for 30 minutes increased glucose transport into L6-GLUT4myc cells without altering surface GLUT4 content, which increased only thereafter. The total amount of GLUT4 protein remained unchanged among the groups studied. The surface GLUT1 content of L6-GLUT1myc cells also remained unaltered after T(3) treatment; however, in these cells glucose transport was not stimulated by T(3). In wild-type L6 cells, although T(3) treatment increased the total amount of GLUT3, it did not change the surface GLUT3 content. Moreover, within 30 minutes, T(3) stimulation of glucose uptake was additive to that of insulin in L6-GLUT4myc cells. As expected, insulin elevated surface GLUT4 content and glucose uptake. However, interestingly, surface GLUT4 content remained unchanged or even dropped with T(3) plus insulin. These data reveal that T(3) rapidly increases glucose uptake in L6-GLUT4myc cells, which, at least for 30 minutes, did not depend on an increment in GLUT4 at the cell surface yet potentiates insulin action. We propose that this rapid T(3) effect involves activation of GLUT4 transporters at the cell surface, but cannot discount the involvement of an unknown GLUT.

  17. The Role of Echocardiography in Hypertrophic Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Jing Ping Sun

    2017-02-01

    Full Text Available Hypertrophic cardiomyopathy (HCM is a common genetic cardiovascular disease and appears in all ethnic groups. HCM is diagnosed on the basis of left ventricular hypertrophy. Echocardiography is a key technique in the diagnosis of HCM, the prognosis of patients with HCM, the management strategy for HCM, and the follow-up of patients with HCM. This review briefly describes and discusses the practical use of established echocardiography techniques and the current and emerging echocardiographic methods that can help physicians in the correct diagnostic and pathophysiological assessment of patients with HCM.

  18. Hypertrophic Cardiomyopathy—Past, Present and Future

    Directory of Open Access Journals (Sweden)

    Alphonsus C. Liew

    2017-12-01

    Full Text Available Hypertrophic cardiomyopathy (HCM is the most common genetic cardiomyopathy with a prevalence of 1 in 500 in the general population. Since the first pathological case series at post mortem in 1957, we have come a long way in its understanding, diagnosis and management. Here, we will describe the history of our understanding of HCM including the initial disease findings, diagnostic methods and treatment options. We will review the current guidelines for the diagnosis and management of HCM, current gaps in the evidence base and discuss the new and promising developments in this field.

  19. Blepharoptosis and hypertrophic osteoarthropathy: A case report

    Directory of Open Access Journals (Sweden)

    Aysun Sanal Dogan

    2016-01-01

    Full Text Available A 52-year-old male patient presented to our hospital with a history of secondary hypertrophic osteoarthropathy (HOA associated with an abdominal neoplasia and blepharoptosis. He had finger clubbing, hyperhidrosis, and hypertrichosis. He also had a recent history of extensive abdominal surgery with a pathology report of myelolipoma. Routine blood work was unremarkable. Upper eyelid reconstruction with blepharoplasty, upper eyelid wedge resection, and brow suspension was performed to address his eyelid concerns. By this case report, we would like to attract notice that the eyelid involvement may be a part of HOA and to emphasize the importance of systemic and pathologic evaluation in failed blepharoptosis surgery.

  20. Hypertrophic Cardiomyopathy—Past, Present and Future

    Science.gov (United States)

    Liew, Alphonsus C.; Vassiliou, Vassilios S.; Cooper, Robert; Raphael, Claire E.

    2017-01-01

    Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiomyopathy with a prevalence of 1 in 500 in the general population. Since the first pathological case series at post mortem in 1957, we have come a long way in its understanding, diagnosis and management. Here, we will describe the history of our understanding of HCM including the initial disease findings, diagnostic methods and treatment options. We will review the current guidelines for the diagnosis and management of HCM, current gaps in the evidence base and discuss the new and promising developments in this field. PMID:29231893

  1. Increased thalamic gamma band activity correlates with symptom relief following deep brain stimulation in humans with Tourette's syndrome.

    Science.gov (United States)

    Maling, Nicholas; Hashemiyoon, Rowshanak; Foote, Kelly D; Okun, Michael S; Sanchez, Justin C

    2012-01-01

    Tourette syndrome (TS) is an idiopathic, childhood-onset neuropsychiatric disorder, which is marked by persistent multiple motor and phonic tics. The disorder is highly disruptive and in some cases completely debilitating. For those with severe, treatment-refractory TS, deep brain stimulation (DBS) has emerged as a possible option, although its mechanism of action is not fully understood. We performed a longitudinal study of the effects of DBS on TS symptomatology while concomitantly examining neurophysiological dynamics. We present the first report of the clinical correlation between the presence of gamma band activity and decreased tic severity. Local field potential recordings from five subjects implanted in the centromedian nucleus (CM) of the thalamus revealed a temporal correlation between the power of gamma band activity and the clinical metrics of symptomatology as measured by the Yale Global Tic Severity Scale and the Modified Rush Tic Rating Scale. Additional studies utilizing short-term stimulation also produced increases in gamma power. Our results suggest that modulation of gamma band activity in both long-term and short-term DBS of the CM is a key factor in mitigating the pathophysiology associated with TS.

  2. Sleep deprivation prevents stimulation-induced increases of levels of P-CREB and BDNF: protection by caffeine.

    Science.gov (United States)

    Alhaider, Ibrahim A; Aleisa, Abdulaziz M; Tran, Trinh T; Alkadhi, Karim A

    2011-04-01

    It is well known that caffeine and sleep deprivation have opposing effects on learning and memory; therefore, this study was undertaken to determine the effects of chronic (4wks) caffeine treatment (0.3g/l in drinking water) on long-term memory deficit associated with 24h sleep deprivation. Animals were sleep deprived using the modified multiple platform method. The results showed that chronic caffeine treatment prevented the impairment of long-term memory as measured by performance in the radial arm water maze task and normalized L-LTP in area CA1 of the hippocampi of sleep-deprived anesthetized rats. Sleep deprivation prevents the high frequency stimulation-induced increases in the levels of phosphorylated-cAMP response element binding protein (P-CREB) and brain-derived neurotrophic factor (BDNF) seen during the expression of late phase long-term potentiation (L-LTP). However, chronic caffeine treatment prevented the effect of sleep-deprivation on the stimulated levels of P-CREB and BDNF. The results suggest that chronic caffeine treatment may protect the sleep-deprived brain probably by preserving the levels of P-CREB and BDNF. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Increased thalamic gamma band activity correlates with symptom relief following deep brain stimulation in humans with Tourette's syndrome.

    Directory of Open Access Journals (Sweden)

    Nicholas Maling

    Full Text Available Tourette syndrome (TS is an idiopathic, childhood-onset neuropsychiatric disorder, which is marked by persistent multiple motor and phonic tics. The disorder is highly disruptive and in some cases completely debilitating. For those with severe, treatment-refractory TS, deep brain stimulation (DBS has emerged as a possible option, although its mechanism of action is not fully understood. We performed a longitudinal study of the effects of DBS on TS symptomatology while concomitantly examining neurophysiological dynamics. We present the first report of the clinical correlation between the presence of gamma band activity and decreased tic severity. Local field potential recordings from five subjects implanted in the centromedian nucleus (CM of the thalamus revealed a temporal correlation between the power of gamma band activity and the clinical metrics of symptomatology as measured by the Yale Global Tic Severity Scale and the Modified Rush Tic Rating Scale. Additional studies utilizing short-term stimulation also produced increases in gamma power. Our results suggest that modulation of gamma band activity in both long-term and short-term DBS of the CM is a key factor in mitigating the pathophysiology associated with TS.

  4. Cubital tunnel syndrome caused by hypertrophic burn scarring: Sonographic envisage

    Directory of Open Access Journals (Sweden)

    Alparslan Bayram Carli

    2015-08-01

    Full Text Available In nerve entrapment syndromes, an electrodiagnostic study during physical examination would usually suffice to assess localization of injury. However, in daily clinical practice, sometimes it may be necessary to depict the insight; in other words to use an imaging tool. From this point of view, with its manifold advantages, ultrasound (US is superior to other imaging technologies such as magnetic resonance imaging (MRI. According to a study, US increased the sensitivity of electrodiagnostic studies from 78% to 98%. By presenting a patient with cubital tunnel syndrome caused by hypertrophic scarring, we wanted to highlight the complementary role of US in nerve entrapment syndromes in confirming the entrapment, as well as the usefulness of it in the follow-up period of burn patients. [Hand Microsurg 2015; 4(2.000: 44-46

  5. Hypertrophic cardiomyopathy and ultra-endurance running - two incompatible entities?

    Directory of Open Access Journals (Sweden)

    Wilson Mathew G

    2011-11-01

    Full Text Available Abstract Regular and prolonged exercise is associated with increased left ventricular wall thickness that can overlap with hypertrophic cardiomyopathy (HCM. Differentiating physiological from pathological hypertrophy has important implications, since HCM is the commonest cause of exercise-related sudden cardiac death in young individuals. Most deaths have been reported in intermittent 'start-stop' sports such as football (soccer and basketball. The theory is that individuals with HCM are unable to augment stroke volume sufficiently to meet the demands of endurance sports and are accordingly 'selected-out' of participation in such events. We report the case of an ultra-endurance athlete with 25 years of > 50 km competitive running experience, with genetically confirmed HCM; thereby demonstrating that these can be two compatible entities.

  6. Hypertrophic cardiomyopathy and ultra-endurance running - two incompatible entities?

    Science.gov (United States)

    Wilson, Mathew G; Chandra, Navin; Papadakis, Michael; O'Hanlon, Rory; Prasad, Sanjay K; Sharma, Sanjay

    2011-11-29

    Regular and prolonged exercise is associated with increased left ventricular wall thickness that can overlap with hypertrophic cardiomyopathy (HCM). Differentiating physiological from pathological hypertrophy has important implications, since HCM is the commonest cause of exercise-related sudden cardiac death in young individuals. Most deaths have been reported in intermittent 'start-stop' sports such as football (soccer) and basketball. The theory is that individuals with HCM are unable to augment stroke volume sufficiently to meet the demands of endurance sports and are accordingly 'selected-out' of participation in such events. We report the case of an ultra-endurance athlete with 25 years of > 50 km competitive running experience, with genetically confirmed HCM; thereby demonstrating that these can be two compatible entities.

  7. The 50-Year History, Controversy, and Clinical Implications of Left Ventricular Outflow Tract Obstruction in Hypertrophic Cardiomyopathy: From Idiopathic Hypertrophic Subaortic Stenosis to Hypertrophic Cardiomyopathy

    National Research Council Canada - National Science Library

    Barry J Maron; Martin S Maron; E Douglas Wigle; Eugene Braunwald

    2009-01-01

    ...) clinical descriptions of hypertrophic cardiomyopathy (HCM) and has proved to be a complex phenomenon unique in many respects, as well as arguably the most visible and well-known pathophysiologic component of this heterogeneous disease...

  8. Electrically stimulated resistance training in SCI individuals increases muscle fatigue resistance but not femoral artery size or blood flow.

    Science.gov (United States)

    Sabatier, M J; Stoner, L; Mahoney, E T; Black, C; Elder, C; Dudley, G A; McCully, K

    2006-04-01

    Longitudinal. The purpose of this study was to evaluate the effect of lower extremity resistance training on quadriceps fatigability, femoral artery diameter, and femoral artery blood flow. Academic Institution. Five male chronic spinal cord injury (SCI) individuals (American Spinal Injury Association (ASIA): A complete; C5-T10; 36+/-5 years old) completed 18 weeks of home-based neuromuscular electrical stimulation (NMES) resistance training. Subjects trained the quadriceps muscle group twice a week with four sets of 10 dynamic knee extensions against resistance while in a seated position. All measurements were made before training and after 8, 12, and 18 weeks of training. Ultrasound was used to measure femoral artery diameter and blood flow. Blood flow was measured before and after 5 and 10 min of distal cuff occlusion, and during a 4-min isometric electrical stimulation fatigue protocol. Training resulted in significant increases in weight lifted and muscle mass, as well as a 60% reduction in muscle fatigue (P = 0.001). However, femoral arterial diameter did not increase. The range was 0.44+/-0.03 to 0.46+/-0.05 cm over the four time points (P = 0.70). Resting, reactive hyperemic, and exercise blood flow did not appear to change with training. NMES resistance training improved muscle size and fatigue despite an absence of response in the supplying vasculature. These results suggest that the decreases in arterial caliber and blood flow seen with SCI are not tightly linked to muscle mass and fatigue resistance. In addition, muscle fatigue in SCI patients can be improved without increases in arterial diameter or blood flow capacity.

  9. Neonatal Nicotine Exposure Increases Excitatory Synaptic Transmission and Attenuates Nicotine-stimulated GABA release in the Adult Rat Hippocampus

    Science.gov (United States)

    Damborsky, Joanne C.; Griffith, William H.; Winzer-Serhan, Ursula H.

    2014-01-01

    Developmental exposure to nicotine has been linked to long-lasting changes in synaptic transmission which may contribute to behavioral abnormalities seen in offspring of women who smoke during pregnancy. Here, we examined the long-lasting effects of developmental nicotine exposure on glutamatergic and GABAergic neurotransmission, and on acute nicotine-induced glutamate and GABA release in the adult hippocampus, a structure important in cognitive and emotional behaviors. We utilized a chronic neonatal nicotine treatment model to administer nicotine (6 mg/kg/day) to rat pups from postnatal day (P) 1–7, a period that falls developmentally into the third human trimester. Using whole-cell voltage clamp recordings from CA1 pyramidal neurons in hippocampal slices, we measured excitatory and inhibitory postsynaptic currents in neonatally control- and nicotine-treated young adult males. Neonatal nicotine exposure significantly increased AMPA receptor-mediated spontaneous and evoked excitatory signaling, with no change in glutamate release probability in adults. Conversely, there was no increase in spontaneous GABAergic neurotransmission in nicotine-males. Chronic neonatal nicotine treatment had no effect on acute nicotine-stimulated glutamate release in adults, but acute nicotine-stimulated GABA release was significantly attenuated. Thus, neonatal nicotine exposure results in a persistent net increase in excitation and a concurrent loss of nicotinic acetylcholine receptor (nAChR)-mediated regulation of presynaptic GABA but not glutamate release, which would exacerbate excitation following endogenous or exogenous nAChR activation. Our data underscore an important role for nAChRs in hippocampal excitatory synapse development, and suggest selective long-term changes at specific presynaptic nAChRs which together could explain some of the behavioral abnormalities associated with maternal smoking. PMID:24950455

  10. Repeated sessions of functional repetitive transcranial magnetic stimulation increases motor cortex excitability and motor control in survivors of stroke.

    Science.gov (United States)

    Massie, Crystal L; Tracy, Brian L; Paxton, Roger J; Malcolm, Matthew P

    2013-01-01

    To determine the impact of a single-session of repetitive transcranial magnetic stimulation (rTMS) and an rTMS intervention on neurophysiology and motor control in survivors of stroke. Twelve stroke survivors were randomized into functional-rTMS or passive-rTMS conditions. Measures of short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF), and force steadiness (coefficient of variation, CV) at 10 and 20% of maximum voluntary contraction were assessed at baseline and after a single-session of rTMS (post single-session), and again following an intervention of 8 rTMS sessions (2 sessions per day; post-intervention). Functional-rTMS required subjects to exceed a muscle activation threshold assessed by surface electromyography to trigger each rTMS train; the passive-rTMS group received rTMS while relaxed. ICF scores significantly increased following the single-session of functional-rTMS compared to the decrease following passive-rTMS. The increase in APB SICI and ICF scores following the intervention was significantly greater for the functional-rTMS group compared to the decreases following passive-rTMS. The groups were significantly different in the CV of force (20%) following the single-session of rTMS, and in the 10 and 20% tasks following the intervention. The functional-rTMS group increased steadiness overtime, whereas the passive group demonstrated a return to baseline following the intervention session. No differences were observed in first dorsal interosseus (FDI) measures (SICI and ICF) between groups. The functional-rTMS protocol enhanced cortical excitability following a single-session and after repeated sessions and improved steadiness, whereas the passive stimulation protocol tended to decrease excitation and no improvements in steadiness were observed.

  11. Keloids and Hypertrophic Scars: Update and Future Directions

    Directory of Open Access Journals (Sweden)

    Chenyu Huang, MD, PhD

    2013-07-01

    Full Text Available Summary: The development of cutaneous pathological scars, namely, hypertrophic scars (HSs and keloids, involves complex pathways, and the exact mechanisms by which they are initiated, evolved, and regulated remain to be fully elucidated. The generally held concepts that keloids and HSs represent “aberrant wound healing” or that they are “characterized by hyalinized collagen bundles” have done little to promote their accurate clinicopathological classification or to stimulate research into the specific causes of these scars and effective preventative therapies. To overcome this barrier, we review here the most recent findings regarding the pathology and pathogenesis of keloids and HSs. The aberrations of HSs and keloids in terms of the inflammation, proliferation, and remodeling phases of the wound healing process are described. In particular, the significant roles that the extracellular matrix and the epidermal and dermal layers of skin play in scar pathogenesis are examined. Finally, the current hypotheses of pathological scar etiology that should be tested by basic and clinical investigators are detailed. Therapies that have been found to be effective are described, including several that evolved directly from the aforementioned etiology hypotheses. A better understanding of pathological scar etiology and manifestations will improve the clinical and histopathological classification and treatment of these important lesions.

  12. Recombinant human granulocyte colony-stimulating factor increases circulating CD34-postive cells in patients with AIDS

    DEFF Research Database (Denmark)

    Nielsen, S D; Dam-Larsen, S; Nielsen, C

    1997-01-01

    .e., the circulating hematopoietic progenitor cells (CD34 cells) in patients with AIDS, using the recombinant human granulocyte colony-stimulating factor (G-CSF). Eight patients with AIDS were treated with G-CSF for neutropenia (... G-CSF for 3-5 consecutive days. Within 5 days of initiation of G-CSF therapy, an increase in the absolute neutrophil count (ANC) was seen in all patients. There was a median increase in ANC from 0.4 to 3.4 x 10(9)/l. In addition, G-CSF treatment significantly increased the absolute number of CD34...... cells. The median increase in CD34 cells was from 0.8 to 2.2 x 10(6)/l. Finally, using a highly sensitive HIV-1 RNA PCR, we found that treatment of AIDS patients with G-CSF did not lead to enhanced HIV replication. These observations indicate that G-CSF may be used to mobilize CD34 cells in patients...

  13. CRF1 receptor activation increases the response of neurons in the basolateral nucleus of the amygdala to afferent stimulation

    Directory of Open Access Journals (Sweden)

    2008-07-01

    Full Text Available The basolateral nucleus (BLA of the amygdala contributes to the consolidation of memories for emotional or stressful events. The nucleus contains a high density of CRF1 receptors that are activated by corticotropin-releasing factor (CRF. Modulation of the excitability of neurons in the BLA by CRF may regulate the immediate response to stressful events and the formation of associated memories. In the present study, CRF was found to increase the amplitude of field potentials recorded in the BLA following excitatory afferent stimulation, in vitro. The increase was mediated by CRF1 receptors, since it could be blocked by the selective, non-peptide antagonists, NBI30775 and NBI35583, but not by the CRF2-selective antagonist, astressin 2B. Furthermore, the CRF2-selective agonist, urocortin II had no effect on field potential amplitude. The increase induced by CRF was long-lasting, could not be reversed by subsequent administration of NBI35583, and required the activation of protein kinase C. This effect of CRF in the BLA may be important for increasing the salience of aversive stimuli under stressful conditions, and for enhancing the consolidation of associated memories. The results provide further justification for studying the efficacy of selective antagonists of the CRF1 receptor to reduce memory formation linked to emotional or traumatic events, and suggest that these compounds might be useful as prophylactic treatment for stress-related illness such as post-traumatic stress disorder.

  14. Mechanical and energetic properties of papillary muscle from ACTC E99K transgenic mouse models of hypertrophic cardiomyopathy

    Science.gov (United States)

    Song, Weihua; Vikhorev, Petr G.; Kashyap, Mavin N.; Rowlands, Christina; Ferenczi, Michael A.; Woledge, Roger C.; MacLeod, Kenneth; Curtin, Nancy A.

    2013-01-01

    We compared the contractile performance of papillary muscle from a mouse model of hypertrophic cardiomyopathy [α-cardiac actin (ACTC) E99K mutation] with nontransgenic (non-TG) littermates. In isometric twitches, ACTC E99K papillary muscle produced three to four times greater force than non-TG muscle under the same conditions independent of stimulation frequency and temperature, whereas maximum isometric force in myofibrils from these muscles was not significantly different. ACTC E99K muscle relaxed slower than non-TG muscle in both papillary muscle (1.4×) and myofibrils (1.7×), whereas the rate of force development after stimulation was the same as non-TG muscle for both electrical stimulation in intact muscle and after a Ca2+ jump in myofibrils. The EC50 for Ca2+ activation of force in myofibrils was 0.39 ± 0.33 μmol/l in ACTC E99K myofibrils and 0.80 ± 0.11 μmol/l in non-TG myofibrils. There were no significant differences in the amplitude and time course of the Ca2+ transient in myocytes from ACTC E99K and non-TG mice. We conclude that hypercontractility is caused by higher myofibrillar Ca2+ sensitivity in ACTC E99K muscles. Measurement of the energy (work + heat) released in actively cycling heart muscle showed that for both genotypes, the amount of energy turnover increased with work done but with decreasing efficiency as energy turnover increased. Thus, ACTC E99K mouse heart muscle produced on average 3.3-fold more work than non-TG muscle, and the cost in terms of energy turnover was disproportionately higher than in non-TG muscles. Efficiency for ACTC E99K muscle was in the range of 11–16% and for non-TG muscle was 15–18%. PMID:23604709

  15. Rupture of mitral valve chordae in hypertrophic cardiomyopathy.

    Science.gov (United States)

    Boissier, Florence; Achkouty, Guy; Bruneval, Patrick; Fabiani, Jean-Noël; Nguyen, Anh Tuan; Riant, Elisabeth; Desnos, Michel; Hagège, Albert

    2015-04-01

    While occasional reports of mitral valve chordal rupture have been described in hypertrophic cardiomyopathy, the exact prevalence and characteristics of this event in a large medical cohort have not been reported. To assess the prevalence of mitral valve chordal rupture in hypertrophic cardiomyopathy and the clinical, echocardiographic, surgical and histological profiles of those patients. We searched for patients with mitral valve chordal rupture diagnosed by echocardiography among all electronic files of patients admitted to our centre for hypertrophic cardiomyopathy between 2000 and 2010. Among 580 patients admitted for hypertrophic cardiomyopathy, six patients (1%, 5 men, age 68-71 years) presented with mitral valve chordal rupture, symptomatic in five cases, always involving the posterior mitral leaflet. In all cases, echocardiography before rupture showed mitral valve systolic anterior motion, with anterior (and not posterior) leaflet elongation compared with a random sample of patients with non-obstructive hypertrophic cardiomyopathy (P=0.006) (and similar to that observed in obstructive hypertrophic cardiomyopathy). Significant resting left ventricular outflow tract obstruction was always present before rupture and disappeared after rupture in the five cases requiring mitral valve surgery for severe mitral regurgitation. Histological findings were consistent with extensive myxomatous degeneration in all cases. Mitral valve chordal rupture is: infrequent in hypertrophic cardiomyopathy; occurs in aged patients with obstructive disease; involves, essentially, the posterior mitral leaflet; and causes, in general, severe mitral regurgitation requiring surgery. Myxomatous degeneration may be the substrate for rupture in these patients. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  16. Cheating the CHA2DS2-VASc Score: Thromboembolism in Apical Hypertrophic Cardiomyopathy

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    Robin A. P. Weir

    2014-01-01

    Full Text Available Atrial fibrillation increases the risk of systemic thromboembolism in general and stroke in particular. Not all patients who develop atrial fibrillation are at significantly heightened risk of thromboembolic complications, however, with the development of risk scoring systems aiding clinicians in determining whether formal anticoagulation is mandated. The most commonly used contemporary scoring systems—CHADS2 and CHA2DS2-VASc—provide a reliable means of assessing stroke risk, but certain cardiac conditions are associated with an increased incidence of thromboembolism without impacting on these risk scores. Hypertrophic cardiomyopathy, with its apical variant, is such a condition. We present a case of a patient with apical hypertrophic cardiomyopathy and atrial fibrillation who suffered dire thromboembolic consequences despite a reassuringly low CHA2DS2-VASc score and suggest that this scoring system is modified to incorporate the thromboembolic risk inherent to certain cardiomyopathies irrespective of impairment of left ventricular systolic dysfunction or clinical heart failure.

  17. Effects of Increasing Neuromuscular Electrical Stimulation Current Intensity on Cortical Sensorimotor Network Activation: A Time Domain fNIRS Study.

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    Makii Muthalib

    Full Text Available Neuroimaging studies have shown neuromuscular electrical stimulation (NMES-evoked movements activate regions of the cortical sensorimotor network, including the primary sensorimotor cortex (SMC, premotor cortex (PMC, supplementary motor area (SMA, and secondary somatosensory area (S2, as well as regions of the prefrontal cortex (PFC known to be involved in pain processing. The aim of this study, on nine healthy subjects, was to compare the cortical network activation profile and pain ratings during NMES of the right forearm wrist extensor muscles at increasing current intensities up to and slightly over the individual maximal tolerated intensity (MTI, and with reference to voluntary (VOL wrist extension movements. By exploiting the capability of the multi-channel time domain functional near-infrared spectroscopy technique to relate depth information to the photon time-of-flight, the cortical and superficial oxygenated (O2Hb and deoxygenated (HHb hemoglobin concentrations were estimated. The O2Hb and HHb maps obtained using the General Linear Model (NIRS-SPM analysis method, showed that the VOL and NMES-evoked movements significantly increased activation (i.e., increase in O2Hb and corresponding decrease in HHb in the cortical layer of the contralateral sensorimotor network (SMC, PMC/SMA, and S2. However, the level and area of contralateral sensorimotor network (including PFC activation was significantly greater for NMES than VOL. Furthermore, there was greater bilateral sensorimotor network activation with the high NMES current intensities which corresponded with increased pain ratings. In conclusion, our findings suggest that greater bilateral sensorimotor network activation profile with high NMES current intensities could be in part attributable to increased attentional/pain processing and to increased bilateral sensorimotor integration in these cortical regions.

  18. Transmastoid galvanic stimulation does not affect the vergence-mediated gain increase of the human angular vestibulo-ocular reflex.

    Science.gov (United States)

    Migliaccio, Americo A; Della Santina, Charles C; Carey, John P

    2013-02-01

    Vergence is one of several viewing contexts that require an increase in the angular vestibular-ocular reflex (aVOR) response. A previous monkey study found that the vergence-mediated gain (eye/head velocity) increase of the aVOR was attenuated by 64 % when anodic currents, which preferentially lower the activity of irregularly firing vestibular afferents, were delivered to both labyrinths. We sought to determine whether there was similar evidence implicating a role for irregular afferents in the vergence-mediated gain increase of the human aVOR. Our study is based upon analysis of the aVOR evoked by head rotations, delivered passively while subjects viewed a near (15 cm) or far (124 cm) target and applying galvanic vestibular stimulation (GVS) via surface electrodes. We tested 12 subjects during 2-3 sessions each. Vestibular stimuli consisted of passive whole-body rotations (sinusoids from 0.05-3 Hz and 12-25°/s, and transients with peak ~15°, 50°/s, 500°/s(2)) and head-on-body impulses (peak ~30°, 150°/s, 3,000°/s(2)). GVS was on for 10 s every 20 s. All polarity combinations were tested, with emphasis on uni- and bi-lateral anodic inhibition. The average stimulus current was 5.9 ± 1.6 mA (range: 3-9.5 mA), vergence angle (during near viewing) was 22.6 ± 2.8° and slow-phase eye velocity caused by left anodic current stimulation with head stationary was -3.4 ± 1.1°/s, -0.2 ± 0.6°/s and 2.5 ± 1.4°/s (torsion, vertical, horizontal). No statistically significant GVS effects were observed, suggesting that surface electrode GVS has no effect on the vergence-mediated gain increase of the aVOR at the current levels (~6 mA) tolerated by most humans. We conclude that clinically practical transmastoid GVS does not effectively silence irregular afferents and hypothesize that currents >10 mA are needed to reproduce the monkey results.

  19. Contributions of ADP and ATP to the increase in skeletal muscle blood flow after manual acupuncture stimulation in rats.

    Science.gov (United States)

    Nagaoka, S; Shinbara, H; Okubo, M; Kawakita, T; Hino, K; Sumiya, E

    2016-06-01

    To investigate the contributions of adenosine triphosphate (ATP) and adenosine diphosphate (ADP) to the increase in skeletal muscle blood flow (MBF) observed following manual acupuncture (MA) stimulation in rats. Male Sprague-Dawley rats were used as experimental animals (300-370 g, n=40). MA was applied to the right tibialis anterior muscle (TA) for 1 min using a stainless steel acupuncture needle. In eight rats, high-performance liquid chromatography with the microdialysis technique was used to measure local extracellular concentrations of ATP, ADP, adenosine monophosphate (AMP), and adenosine in the TA. In the remaining 32 rats, fluorescent microspheres (15 µm in diameter) were used to measure MBF in the TA following pre-treatment with either the P2 receptor antagonist suramin (100 mg/kg intra-arterially) or saline (control) (n=16 each). Rats receiving MA (Suramin+MA and Saline+MA groups, n=8 each) were compared with untreated rats (Suramin and Saline groups, n=8). MA significantly increased the local extracellular concentration of ATP, ADP, and adenosine (pvs 30 min after MA). In addition, MA significantly increased MBF in rats pre-treated with saline or suramin (pvs Saline+MA; pvs Suramin+MA, respectively). However, suramin significantly suppressed this MA-induced increase in MBF (pvs Suramin+MA). These results suggest that both ATP and ADP partially contribute to the MA-induced increase in MBF via P2 receptors. However, further studies are needed to clarify the contributions of other vasodilators. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  20. [Utility of cardiovascular magnetic resonance in hypertrophic cardiomyopathy: when is it superior to echocardiography?].

    Science.gov (United States)

    Kammoun, I; Marrakchi, S; Zidi, A; Ibn ElHaj, Z; Naccache, S; Ben Amara, W; Jebri, F; Bennour, E; Kachboura, S

    2015-02-01

    The diagnosis of hypertrophic cardiomyopathy is usually established by echocardiography. Recently, there has been greatly increased use of cardiac magnetic resonance (CMR) because of its precise determination of myocardial anatomy and the depiction of myocardial fibrosis. In this review, we describe the role of echocardiography and magnetic resonance in the assessment of this complex disease. In conclusion, there is a complementarity between cardiovascular magnetic resonance imaging and echocardiography for the diagnosis and the management of HCM. Copyright © 2014. Published by Elsevier SAS.

  1. Asymmetric left ventricular hypertrophy associated with morbid obesity mimicking familial hypertrophic cardiomyopathy.

    Science.gov (United States)

    Wong, Raymond Ching-Chiew; Tan, Kong Bing

    2014-12-01

    Asymmetric septal hypertrophy with systolic anterior motion of the mitral valve is frequently a phenotypic, but not pathognomonic, expression of genetic hypertrophic cardiomyopathy (HCM) with or without obstruction. It can, however, be associated nonspecifically with other forms of increased left ventricular (LV) afterload. We herein report the case of a young man with obesity cardiomyopathy and heart failure who presented with asymmetric septal hypertrophy and marked LV hypertrophy, and endomyocardial biopsy ruled out genetic HCM.

  2. Addition of Wollastonite Fibers to Calcium Phosphate Cement Increases Cell Viability and Stimulates Differentiation of Osteoblast-Like Cells

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    Juliana Almeida Domingues

    2017-01-01

    Full Text Available Calcium phosphate cement (CPC that is based on α-tricalcium phosphate (α-TCP is considered desirable for bone tissue engineering because of its relatively rapid degradation properties. However, such cement is relatively weak, restricting its use to areas of low mechanical stress. Wollastonite fibers (WF have been used to improve the mechanical strength of biomaterials. However, the biological properties of WF remain poorly understood. Here, we tested the response of osteoblast-like cells to being cultured on CPC reinforced with 5% of WF (CPC-WF. We found that both types of cement studied achieved an ion balance for calcium and phosphate after 3 days of immersion in culture medium and this allowed subsequent long-term cell culture. CPC-WF increased cell viability and stimulated cell differentiation, compared to nonreinforced CPC. We hypothesize that late silicon release by CPC-WF induces increased cell proliferation and differentiation. Based on our findings, we propose that CPC-WF is a promising material for bone tissue engineering applications.

  3. Vinegar Consumption Increases Insulin-Stimulated Glucose Uptake by the Forearm Muscle in Humans with Type 2 Diabetes.

    Science.gov (United States)

    Mitrou, Panayota; Petsiou, Eleni; Papakonstantinou, Emilia; Maratou, Eirini; Lambadiari, Vaia; Dimitriadis, Panayiotis; Spanoudi, Filio; Raptis, Sotirios A; Dimitriadis, George

    2015-01-01

    Vinegar has been shown to have a glucose-lowering effect in patients with glucose abnormalities. However, the mechanisms of this effect are still obscure. The aim of this randomised, crossover study was to investigate the effect of vinegar on glucose metabolism in muscle which is the most important tissue for insulin-stimulated glucose disposal. Eleven subjects with DM2 consumed vinegar or placebo (at random order on two separate days, a week apart), before a mixed meal. Plasma glucose, insulin, triglycerides, nonesterified fatty acids (NEFA), and glycerol were measured preprandially and at 30-60 min for 300 min postprandially from the radial artery and from a forearm vein. Muscle blood flow was measured with strain-gauge plethysmography. Glucose uptake was calculated as the arteriovenous difference of glucose multiplied by blood flow. Vinegar compared to placebo (1) increased forearm glucose uptake (p = 0.0357), (2) decreased plasma glucose (p = 0.0279), insulin (p = 0.0457), and triglycerides (p = 0.0439), and (3) did not change NEFA and glycerol. In DM2 vinegar reduces postprandial hyperglycaemia, hyperinsulinaemia, and hypertriglyceridaemia without affecting lipolysis. Vinegar's effect on carbohydrate metabolism may be partly accounted for by an increase in glucose uptake, demonstrating an improvement in insulin action in skeletal muscle. This trial is registered with Clinicaltrials.gov NCT02309424.

  4. Vinegar Consumption Increases Insulin-Stimulated Glucose Uptake by the Forearm Muscle in Humans with Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Panayota Mitrou

    2015-01-01

    Full Text Available Background and Aims. Vinegar has been shown to have a glucose-lowering effect in patients with glucose abnormalities. However, the mechanisms of this effect are still obscure. The aim of this randomised, crossover study was to investigate the effect of vinegar on glucose metabolism in muscle which is the most important tissue for insulin-stimulated glucose disposal. Materials and Methods. Eleven subjects with DM2 consumed vinegar or placebo (at random order on two separate days, a week apart, before a mixed meal. Plasma glucose, insulin, triglycerides, nonesterified fatty acids (NEFA, and glycerol were measured preprandially and at 30–60 min for 300 min postprandially from the radial artery and from a forearm vein. Muscle blood flow was measured with strain-gauge plethysmography. Glucose uptake was calculated as the arteriovenous difference of glucose multiplied by blood flow. Results. Vinegar compared to placebo (1 increased forearm glucose uptake (p=0.0357, (2 decreased plasma glucose (p=0.0279, insulin (p=0.0457, and triglycerides (p=0.0439, and (3 did not change NEFA and glycerol. Conclusions. In DM2 vinegar reduces postprandial hyperglycaemia, hyperinsulinaemia, and hypertriglyceridaemia without affecting lipolysis. Vinegar’s effect on carbohydrate metabolism may be partly accounted for by an increase in glucose uptake, demonstrating an improvement in insulin action in skeletal muscle. This trial is registered with Clinicaltrials.gov NCT02309424.

  5. Breast feeding increases vasoconstriction induced by electrical field stimulation in rat mesenteric artery. Role of neuronal nitric oxide and ATP.

    Directory of Open Access Journals (Sweden)

    Javier Blanco-Rivero

    Full Text Available OBJECTIVES: The aim of this study was to investigate in rat mesenteric artery whether breast feeding (BF affects the vasomotor response induced by electrical field stimulation (EFS, participation by different innervations in the EFS-induced response and the mechanism/s underlying these possible modifications. METHODS: Experiments were performed in female Sprague-Dawley rats (3 months old, divided into three groups: Control (in oestrous phase, mothers after 21 days of BF, and mothers that had recovered their oestral cycle (After BF, in oestrous phase. Vasomotor response to EFS, noradrenaline (NA and nitric oxide (NO donor DEA-NO were studied. Neuronal NO synthase (nNOS and phosphorylated nNOS (P-nNOS protein expression were analysed and NO, superoxide anion (O(2(.-, NA and ATP releases were also determined. RESULTS: EFS-induced contraction was higher in the BF group, and was recovered after BF. 1 µmol/L phentolamine decreased the response to EFS similarly in control and BF rats. NA vasoconstriction and release were similar in both experimental groups. ATP release was higher in segments from BF rats. 0.1 mmol/L L-NAME increased the response to EFS in both control and BF rats, but more so in control animals. BF decreased NO release and did not modify O(2(.- production. Vasodilator response to DEA-NO was similar in both groups, while nNOS and P-nNOS expressions were decreased in segments from BF animals. CONCLUSION: Breast feeding increases EFS-induced contraction in mesenteric arteries, mainly through the decrease of neuronal NO release mediated by decreased nNOS and P-nNOS expression. Sympathetic function is increased through the increased ATP release in BF rats.

  6. Paired motor cortex and cervical epidural electrical stimulation timed to converge in the spinal cord promotes lasting increases in motor responses.

    Science.gov (United States)

    Mishra, Asht M; Pal, Ajay; Gupta, Disha; Carmel, Jason B

    2017-11-15

    Pairing motor cortex stimulation and spinal cord epidural stimulation produced large augmentation in motor cortex evoked potentials if they were timed to converge in the spinal cord. The modulation of cortical evoked potentials by spinal cord stimulation was largest when the spinal electrodes were placed over the dorsal root entry zone. Repeated pairing of motor cortex and spinal cord stimulation caused lasting increases in evoked potentials from both sites, but only if the time between the stimuli was optimal. Both immediate and lasting effects of paired stimulation are likely mediated by convergence of descending motor circuits and large diameter afferents onto common interneurons in the cervical spinal cord. Convergent activity in neural circuits can generate changes at their intersection. The rules of paired electrical stimulation are best understood for protocols that stimulate input circuits and their targets. We took a different approach by targeting the interaction of descending motor pathways and large diameter afferents in the spinal cord. We hypothesized that pairing stimulation of motor cortex and cervical spinal cord would strengthen motor responses through their convergence. We placed epidural electrodes over motor cortex and the dorsal cervical spinal cord in rats; motor evoked potentials (MEPs) were measured from biceps. MEPs evoked from motor cortex were robustly augmented with spinal epidural stimulation delivered at an intensity below the threshold for provoking an MEP. Augmentation was critically dependent on the timing and position of spinal stimulation. When the spinal stimulation was timed to coincide with the descending volley from motor cortex stimulation, MEPs were more than doubled. We then tested the effect of repeated pairing of motor cortex and spinal stimulation. Repetitive pairing caused strong augmentation of cortical MEPs and spinal excitability that lasted up to an hour after just 5 min of pairing. Additional physiology

  7. Cardiovascular magnetic resonance in hypertrophic cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Shiozaki, Afonso Akio; Parga, Jose Rodrigues; Arteaga, Edmundo; Rochitte, Carlos Eduardo [Sao Paulo Univ. (USP), SP (Brazil). Instituto do Coracao. Setor de Tomografia Computarizada e Ressonancia Magnetica Cardiovascular]. E-mail: rochitte@incor.usp.br; Kim, Raymond J. [Duke Cardiovascular Magnetic Resonance Center, Durham, NC (United States); Tassi, Eduardo Marinho [Diagnosticos da America S.A., Rio de Janeiro, RJ (Brazil). Sector of Cardiovascular Magnetic Resonance and Computed Tomography

    2007-03-15

    Hypertrophic cardiomyopathy (HCM) is the most frequent genetic cardiac disease that causes sudden death in young people, with an incidence of 1:500 adults. The routinely used criteria for worst prognosis have limited sensitivity and specificity. Thus, the estimated risk of evolving to dilated cardiomyopathy or sudden death is somewhat inaccurate, leading to management uncertainty of HCM patients. Therefore, an accurate noninvasive method for the diagnosis of HCM with prognostic value is of great importance. In the last years, Cardiovascular Magnetic Resonance (CMR) emerged not only as a diagnostic tool, but also as a study with prognostic values, by characterizing myocardial fibrosis with great accuracy in HCM patients. Additionally, CMR identifies the types of hypertrophy, analyses the ventricular function, estimates the intraventricular gradient and allows the determination of differential diagnosis. Moreover, CMR can uniquely access myocardial fibrosis in HCM. (author)

  8. Electrodiagnostic evaluation in feline hypertrophic muscular dystrophy.

    Science.gov (United States)

    Howard, J; Jaggy, A; Busato, A; Gaschen, F

    2004-07-01

    Standard needle electromyography (EMG) of 56 muscles and nerve conduction velocities (NCV) of the ulnar and common peroneal nerves were investigated in each of six cats affected with hypertrophic feline muscular dystrophy, 10 related heterozygote carriers and 10 normal cats. The EMG findings were considered normal in carrier and control cats, and consisted of 33% normal readings, 22% myotonic discharges, 18% fibrillation potentials, 11% prolonged insertional potentials, 10% complex repetitive discharges and 6% positive sharp waves in affected cats. Muscles of the proximal limbs were most frequently affected. No differences in NCV were found between the three cat groups. It was concluded that dystrophin-deficient dystrophic cats have widespread and frequent EMG changes, predominantly myotonic discharges and fibrillation potentials, which are most pronounced in the proximal appendicular muscles.

  9. MT-CYB mutations in hypertrophic cardiomyopathy

    DEFF Research Database (Denmark)

    Hagen, Christian M; Aidt, Frederik H; Havndrup, Ole

    2013-01-01

    Mitochondrial dysfunction is a characteristic of heart failure. Mutations in mitochondrial DNA, particularly in MT-CYB coding for cytochrome B in complex III (CIII), have been associated with isolated hypertrophic cardiomyopathy (HCM). We hypothesized that MT-CYB mutations might play an important...... and m.15482T>C; p.S246P were identified. Modeling showed that the p.C93Y mutation leads to disruption of the tertiary structure of Cytb by helix displacement, interfering with protein-heme interaction. The p.S246P mutation induces a diproline structure, which alters local secondary structure and induces...... of HCM patients. We propose that further patients with HCM should be examined for mutations in MT-CYB in order to clarify the role of these variants....

  10. Recent Advances in the Molecular Genetics of Familial Hypertrophic Cardiomyopathy in South Asian Descendants

    Science.gov (United States)

    Kraker, Jessica; Viswanathan, Shiv Kumar; Knöll, Ralph; Sadayappan, Sakthivel

    2016-01-01

    The South Asian population, numbered at 1.8 billion, is estimated to comprise around 20% of the global population and 1% of the American population, and has one of the highest rates of cardiovascular disease. While South Asians show increased classical risk factors for developing heart failure, the role of population-specific genetic risk factors has not yet been examined for this group. Hypertrophic cardiomyopathy (HCM) is one of the major cardiac genetic disorders among South Asians, leading to contractile dysfunction, heart failure, and sudden cardiac death. This disease displays autosomal dominant inheritance, and it is associated with a large number of variants in both sarcomeric and non-sarcomeric proteins. The South Asians, a population with large ethnic diversity, potentially carries region-specific polymorphisms. There is high variability in disease penetrance and phenotypic expression of variants associated with HCM. Thus, extensive studies are required to decipher pathogenicity and the physiological mechanisms of these variants, as well as the contribution of modifier genes and environmental factors to disease phenotypes. Conducting genotype-phenotype correlation studies will lead to improved understanding of HCM and, consequently, improved treatment options for this high-risk population. The objective of this review is to report the history of cardiovascular disease and HCM in South Asians, present previously published pathogenic variants, and introduce current efforts to study HCM using induced pluripotent stem cell-derived cardiomyocytes, next-generation sequencing, and gene editing technologies. The authors ultimately hope that this review will stimulate further research, drive novel discoveries, and contribute to the development of personalized medicine with the aim of expanding therapeutic strategies for HCM. PMID:27840609

  11. Recent Advances in the Molecular Genetics of Familial Hypertrophic Cardiomyopathy in South Asian Descendants

    Directory of Open Access Journals (Sweden)

    Jessica Kraker

    2016-10-01

    Full Text Available The South Asian population, numbered at 1.8 billion, is estimated to comprise around 20% of the global population and 1% of the American population, and has one of the highest rates of cardiovascular disease. While South Asians show increased classical risk factors for developing heart failure, the role of population-specific genetic risk factors has not yet been examined for this group. Hypertrophic cardiomyopathy (HCM is one of the major cardiac genetic disorders among South Asians, leading to contractile dysfunction, heart failure, and sudden cardiac death. This disease displays autosomal dominant inheritance, and it is associated with a large number of variants in both sarcomeric and non-sarcomeric proteins. South Asians, a population with large ethnic diversity, potentially carries region-specific polymorphisms. There is high variability in disease penetrance and phenotypic expression of variants associated with HCM. Thus, extensive studies are required to decipher pathogenicity and the physiological mechanisms of these variants, as well as the contribution of modifier genes and environmental factors to disease phenotypes. Conducting genotype-phenotype correlation studies will lead to improved understanding of HCM and, consequently, improved treatment options for this high-risk population. The objective of this review is to report the history of cardiovascular disease and HCM in South Asians, present previously published pathogenic variants, and introduce current efforts to study HCM using induced pluripotent stem cell-derived cardiomyocytes, next-generation sequencing, and gene editing technologies. The authors ultimately hope that this review will stimulate further research, drive novel discoveries, and contribute to the development of personalized medicine with the aim of expanding therapeutic strategies for HCM.

  12. Current Therapeutic Approach to Hypertrophic Scars

    Directory of Open Access Journals (Sweden)

    Zrinka Bukvić Mokos

    2017-06-01

    Full Text Available Abnormal scarring and its accompanying esthetic, functional, and psychological sequelae still pose significant challe nges. To date, there is no satisfactory prevention or treatment option for hypertrophic scars (HSs, which is mostly due to not completely comprehending the mechanisms underlying their formation. That is why the apprehension of regular and controlled physiological processes of scar formation is of utmost importance when facing hypertrophic scarring, its pathophysiology, prevention, and therapeutic approach. When treating HSs and choosing the best treatment and prevention modality, physicians can choose from a plethora of therapeutic options and many commercially available products, among which currently there is no efficient option that can successfully overcome impaired skin healing. This article reviews current therapeutic approach and emerging therapeutic strategies for the management of HSs, which should be individualized, based on an evaluation of the scar itself, patients’ expectations, and practical, evidence-based guidelines. Clinicians are encouraged to combine various prevention and treatment modalities where combination therapy that includes steroid injections, 5-fluorouracil, and pulsed-dye laser seems to be the most effective. On the other hand, the current therapeutic options are usually empirical and their results are unreliable and unpredictable. Therefore, there is an unmet need for an effective, targeted therapy and prevention, which would be based on an action or a modulation of a particular factor with clarified mechanism of action that has a beneficial effect on wound healing. As the extracellular matrix has a crucial role in cellular and extracellular events that lead to pathological scarring, targeting its components mostly by regulating bone morphogenetic proteins may throw up new therapeutic approach for reduction or prevention of HSs with functionally and cosmetically acceptable outcome.

  13. Hypertrophic Cardiomyopathy (HCM): How Flow Analysis May Drive Medical Management and Surgical Approach

    Science.gov (United States)

    Abraham, Theodore P.

    2011-11-01

    Hypertrophic Cardiomyopathy (HCM) is the most common inherited heart disease and occurs in 1 in 500 persons worldwide regardless of race, age and gender. It is the most common cause of sudden death in the young and also causes heart failure and cardiac arrhythmias. The primary anatomic abnormality is thickening of certain walls, or sometimes global thickening of the left or right ventricle. The patterns of thickening along with increased ventricular stiffness lead to suboptimal ventricular filling and inefficient ejection of blood from the ventricle. Treatment for HCM can be medical or surgical. The choice of therapy is driven by the presence and severity of outflow obstruction. Flow analysis could provide sophisticated information about outflow and inflow ventricular dynamics. These flow dynamics features may enable better medical choices and provide information that would allow superior surgical planning. Associate Professor of Medicine & Director, Hypertrophic Cardiomyopathy Clinic

  14. Melanogenesis stimulation in B16-F10 melanoma cells induces cell cycle alterations, increased ROS levels and a differential expression of proteins as revealed by proteomic analysis

    Energy Technology Data Exchange (ETDEWEB)

    Cunha, Elizabeth S.; Kawahara, Rebeca [Departamento de Bioquimica e Biologia Molecular, Setor de Ciencias Biologicas, Universidade Federal do Parana, P.O. Box 19046, CEP 81531-990, Curitiba, PR (Brazil); Kadowaki, Marina K. [Universidade Estadual do Oeste do Parana, Cascavel, PR (Brazil); Amstalden, Hudson G.; Noleto, Guilhermina R.; Cadena, Silvia Maria S.C.; Winnischofer, Sheila M.B. [Departamento de Bioquimica e Biologia Molecular, Setor de Ciencias Biologicas, Universidade Federal do Parana, P.O. Box 19046, CEP 81531-990, Curitiba, PR (Brazil); Martinez, Glaucia R., E-mail: grmartinez@ufpr.br [Departamento de Bioquimica e Biologia Molecular, Setor de Ciencias Biologicas, Universidade Federal do Parana, P.O. Box 19046, CEP 81531-990, Curitiba, PR (Brazil)

    2012-09-10

    Considering that stimulation of melanogenesis may lead to alterations of cellular responses, besides melanin production, our main goal was to study the cellular effects of melanogenesis stimulation of B16-F10 melanoma cells. Our results show increased levels of the reactive oxygen species after 15 h of melanogenesis stimulation. Following 48 h of melanogenesis stimulation, proliferation was inhibited (by induction of cell cycle arrest in the G1 phase) and the expression levels of p21 mRNA were increased. In addition, melanogenesis stimulation did not induce cellular senescence. Proteomic analysis demonstrated the involvement of proteins from other pathways besides those related to the cell cycle, including protein disulfide isomerase A3, heat-shock protein 70, and fructose biphosphate aldolase A (all up-regulated), and lactate dehydrogenase (down-regulated). In RT-qPCR experiments, the levels of pyruvate kinase M2 mRNA dropped, whereas the levels of ATP synthase (beta-F1) mRNA increased. These data indicate that melanogenesis stimulation of B16-F10 cells leads to alterations in metabolism and cell cycle progression that may contribute to an induction of cell quiescence, which may provide a mechanism of resistance against cellular injury promoted by melanin synthesis. -- Highlights: Black-Right-Pointing-Pointer Melanogenesis stimulation by L-tyrosine+NH{sub 4}Cl in B16-F10 melanoma cells increases ROS levels. Black-Right-Pointing-Pointer Melanogenesis inhibits cell proliferation, and induced cell cycle arrest in the G1 phase. Black-Right-Pointing-Pointer Proteomic analysis showed alterations in proteins of the cell cycle and glucose metabolism. Black-Right-Pointing-Pointer RT-qPCR analysis confirmed alterations of metabolic targets after melanogenesis stimulation.

  15. Low-intensity repetitive magnetic stimulation lowers action potential threshold and increases spike firing in layer 5 pyramidal neurons in vitro.

    Science.gov (United States)

    Tang, Alexander D; Hong, Ivan; Boddington, Laura J; Garrett, Andrew R; Etherington, Sarah; Reynolds, John N J; Rodger, Jennifer

    2016-10-29

    Repetitive transcranial magnetic stimulation (rTMS) has become a popular method of modulating neural plasticity in humans. Clinically, rTMS is delivered at high intensities to modulate neuronal excitability. While the high-intensity magnetic field can be targeted to stimulate specific cortical regions, areas adjacent to the targeted area receive stimulation at a lower intensity and may contribute to the overall plasticity induced by rTMS. We have previously shown that low-intensity rTMS induces molecular and structural plasticity in vivo, but the effects on membrane properties and neural excitability have not been investigated. Here we investigated the acute effect of low-intensity repetitive magnetic stimulation (LI-rMS) on neuronal excitability and potential changes on the passive and active electrophysiological properties of layer 5 pyramidal neurons in vitro. Whole-cell current clamp recordings were made at baseline prior to subthreshold LI-rMS (600 pulses of iTBS, n=9 cells from 7 animals) or sham (n=10 cells from 9 animals), immediately after stimulation, as well as 10 and 20min post-stimulation. Our results show that LI-rMS does not alter passive membrane properties (resting membrane potential and input resistance) but hyperpolarises action potential threshold and increases evoked spike-firing frequency. Increases in spike firing frequency were present throughout the 20min post-stimulation whereas action potential (AP) threshold hyperpolarization was present immediately after stimulation and at 20min post-stimulation. These results provide evidence that LI-rMS alters neuronal excitability of excitatory neurons. We suggest that regions outside the targeted region of high-intensity rTMS are susceptible to neuromodulation and may contribute to rTMS-induced plasticity. Copyright © 2016 IBRO. All rights reserved.

  16. Hypertrophic Synovitis of the Facet Joint Causing Root Pain

    Directory of Open Access Journals (Sweden)

    Koichi Iwatsuki M.D.

    2008-01-01

    Full Text Available Osteoarthritic changes in the facet joints are common in the presence of degenerative disc disease. Changes in the joint capsule accompany changes in the articular surfaces. Intraspinal synovial cysts that cause radicular pain, cauda equina syndrome, and myelopathy have been reported; however, there have been few reports in orthopedic or neurosurgical literature regarding hypertrophic synovitis of the facet joint presenting as an incidental para-articular mass. Here, we report a case of hypertrophic synovitis causing root pain. We describe the case of a 65-year-old man suffering from right sciatica and right leg pain in the L5 nerve-root dermatome for 1 year; magnetic resonance imaging (MRI revealed an enhanced mass around the L4–5 facet joint. We investigated this mass pathologically. After right medial facetectomy, the symptoms resolved. Pathological investigation revealed this mass was hypertrophic synovitis. Hypertrophic synovitis of the facet joint might cause root pain.

  17. Regional ischemia in hypertrophic Langendorff-perfused rat hearts

    NARCIS (Netherlands)

    J.F. Ashruf; C. Ince (Can); H.A. Bruining (Hajo)

    1999-01-01

    textabstractMyocardial hypertrophy decreases the muscle mass-to-vascularization ratio, thereby changing myocardial perfusion. The effect of these changes on myocardial oxygenation in hypertrophic Langendorff-perfused rat hearts was measured using epimyocardial NADH

  18. Hypertrophic Pulmonary Osteoarthropathy Associated with Primary Adenocarcinoma of the Lung

    OpenAIRE

    Ayabe, Hiroyoshi; Hisano, Hiroshi; Oka, Tadayuki; Tsuji, Hiroharu; Hara, Shinsuke; Tagawa, Yutaka; Kawahara, Katsunobu; Tomita, Masaotomita

    1991-01-01

    Hypertrophic pulmonary osteoarthropathy (HPOA) associated with primary lung cancer is reported in a fifty-four-year-old man. Symptoms of HPOA were makedly improved following lung resection for adenocarcinoma of the lung.

  19. Cyanobacteria-phytoplankton dynamics of a hypertrophic African lake

    CSIR Research Space (South Africa)

    Zohary, T

    1995-01-01

    Full Text Available Phytoplankton species composition and abundance were recorded weekly or biweekly for nearly 7 years in a hypertrophic lake ( Hartbeespoort Dam, South Africa), together with a range of physical and chemical parameters. A total of 73 species were...

  20. On the surgical treatment of hypertrophic scars: a comprehensive guideline for the surgical treatment of hypertrophic scars

    NARCIS (Netherlands)

    Stekelenburg, C.M.; van der Wal, M.B.A.; Middelkoop, E.; Niessen, F.B.; van Zuijlen, P.P.M.

    2012-01-01

    Background: Treating the hypertrophic scar remains a challenging problem. It often leaves the clinician with the questions whether, when and how to treat a hypertrophic scar. Methods: This review will focus on the surgical treatment of hypertrophic scars considering the latest research in this

  1. PPARalpha activation and increased dietary lipid oppose thyroid hormone signaling and rescue impaired glucose-stimulated insulin secretion in hyperthyroidism.

    Science.gov (United States)

    Holness, Mark J; Greenwood, Gemma K; Smith, Nicholas D; Sugden, Mary C

    2008-12-01

    The aim of the study was to investigate the impact of hyperthyroidism on the characteristics of the islet insulin secretory response to glucose, particularly the consequences of competition between thyroid hormone and peroxisome proliferator-activated receptor (PPAR)alpha in the regulation of islet adaptations to starvation and dietary lipid-induced insulin resistance. Rats maintained on standard (low-fat/high-carbohydrate) diet or high-fat/low-carbohydrate diet were rendered hyperthyroid (HT) by triiodothyronine (T(3)) administration (1 mg.kg body wt(-1).day(-1) sc, 3 days). The PPARalpha agonist WY14643 (50 mg/kg body wt ip) was administered 24 h before sampling. Glucose-stimulated insulin secretion (GSIS) was assessed during hyperglycemic clamps or after acute glucose bolus injection in vivo and with step-up and step-down islet perifusions. Hyperthyroidism decreased the glucose responsiveness of GSIS, precluding sufficient enhancement of insulin secretion for the degree of insulin resistance, in rats fed either standard diet or high-fat diet. Hyperthyroidism partially opposed the starvation-induced increase in the glucose threshold for GSIS and decrease in glucose responsiveness. WY14643 administration restored glucose tolerance by enhancing GSIS in fed HT rats and relieved the impact of hyperthyroidism to partially oppose islet starvation adaptations. Competition between thyroid hormone receptor (TR) and PPARalpha influences the characteristics of GSIS, such that hyperthyroidism impairs GSIS while PPARalpha activation (and increased dietary lipid) opposes TR signaling and restores GSIS in the fed hyperthyroid state. Increased islet PPARalpha signaling and decreased TR signaling during starvation facilitates appropriate modification of islet function.

  2. Copper oxide nanoparticles stimulate glycolytic flux and increase the cellular contents of glutathione and metallothioneins in cultured astrocytes.

    Science.gov (United States)

    Bulcke, Felix; Dringen, Ralf

    2015-01-01

    Copper oxide nanoparticles (CuO-NPs) are frequently used for industrial or medical applications and are known for their high toxic potential. As little is known so far on the consequences of an exposure of brain cells to such particles, we applied CuO-NPs to cultured primary rat astrocytes and investigated whether such particles affect cell viability and alter their metabolic properties. Astrocytes efficiently accumulated CuO-NPs in a time- and concentration-dependent manner. The cells remained viable during a 24 h incubation with 100 µM copper in the form of CuO-NPs, while higher concentrations of CuO-NPs severely compromised the cell viability. Astrocytes that were exposed for 24 h to 100 µM CuO-NPs showed significantly enhanced extracellular lactate concentrations and increased cellular levels of glutathione and metallothioneins. The CuO-NP-induced increase in lactate release and metallothionein content were prevented by the presence of the membrane-permeable copper chelator tetrathiomolybdate, while this chelator increased already in the absence of CuO-NPs the cellular glutathione content. After removal of the CuO-NPs following a 24 h pre-incubation with 100 µM CuO-NPs, astrocytes maintained during a further 6 h incubation an elevated glycolytic lactate release and exported significantly more glutathione than control cells that had been pre-incubated without CuO-NPs. These data suggest that copper ions which are liberated from internalized CuO-NPs stimulate glycolytic flux as well as the synthesis of glutathione and metallothioneins in cultured viable astrocytes.

  3. Epothilone B impairs functional recovery after spinal cord injury by increasing secretion of macrophage colony-stimulating factor.

    Science.gov (United States)

    Mao, Liang; Gao, Wei; Chen, Shurui; Song, Ying; Song, Changwei; Zhou, Zipeng; Zhao, Haosen; Zhou, Kang; Wang, Wei; Zhu, Kunming; Liu, Chang; Mei, Xifan

    2017-11-02

    The microtubule-stabilizing drug epothilone B (epoB) has shown potential value in the treatment of spinal cord injury (SCI) through diverse mechanisms. However, it remains elusive why a limited overall effect was observed. We aim to investigate the limiting factors underlying functional recovery promoted by epoB. The same SCI model treated by epoB was established as discussed previously. We used a cerebrospinal fluid (CSF) sample to assess the changes in cytokines in milieu of the SCI lesion site after epoB treatment. We then analyzed the source of cytokines, the state of microglia/macrophages/monocytes (M/Ms), and the recruitment of neutrophil in the lesion site by using the results of antibody array. Following these findings, we further evaluated the motor functional recovery caused by the reshaped microenvironment. Systemic administration of epoB significantly increased levels of several cytokines in the CSF of the rat SCI model; macrophage colony-stimulating factor (M-CSF) secreted by intact central nervous system (CNS) cells was one of the cytokines with increased levels. Along with epoB and other cytokines, M-CSF reshapes the SCI milieu by activating the microglias, killing bone marrow-derived macrophages, polarizing the M/M to M1 phenotype, and activating downstream cytokines to exacerbate the SCI injury, but it also increases the expression of neurotrophic factors. Anti-inflammatory therapy using a neutralizing antibody mix shows encouraging results. Using in vivo experiments, our findings indicate that epoB inhibits the SCI functional recovery in many ways by reshaping the milieu, which counteracts the therapeutic efficacy that led to the limited overall effectiveness.

  4. A novel instrument aimed at measuring hypertrophic scar formation

    Energy Technology Data Exchange (ETDEWEB)

    Ramella-Roman, J C; Nguyen, T A; Lemaillet, P [Department of Biomedical Engineering, Catholic University of America (United States); Pavlovich, A R; Jordan, M H; Shupp, J W, E-mail: ramella@cua.edu [Burn Center, Department of Surgery, Washington Hospital Center-MedStar Health Research Institute, Washington, DC (United States)

    2011-01-01

    Hypertrophic scaring is a condition that can occur after thermal trauma and can lead to loss of function and psyco-social complications. Assessment of the development of a hypertrophic scar currently relies on visual inspection and grading. In this paper we propose a system based on polarized illumination and collection capable of capturing images of scars and quantify their roughness. Models of rough surface roughness are ultimately used to quantify the level of roughness of scarred skin compared to normal skin.

  5. Hypertrophic cardiomyopathy with mid-ventricular obstruction and apical aneurysm

    Directory of Open Access Journals (Sweden)

    N.D. Oryshchyn

    2016-11-01

    Full Text Available A case report of apical left ventricular aneurysm in patient with hypertrophic cardiomyopathy with mid-ventricular obstruction (diagnosis and surgical treatment is presented. We revealed apical aneurysm and mid-ventricular obstruction during echocardiography and specified anatomical characteristics of aneurysm during computer tomography. There was no evidence of obstructive coronary artery disease during coronary angiography. Taking into consideration multiple cerebral infarcts, aneurysm resection and left ventricular plastics was performed. Electronic microscopy of myocardium confirmed the diagnosis of hypertrophic cardiomyopathy.

  6. Aberrant α-Adrenergic Hypertrophic Response in Cardiomyocytes from Human Induced Pluripotent Cells

    Directory of Open Access Journals (Sweden)

    Gabor Földes

    2014-11-01

    Full Text Available Cardiomyocytes from human embryonic stem cells (hESC-CMs and induced pluripotent stem cells (hiPSC-CMs represent new models for drug discovery. Although hypertrophy is a high-priority target, we found that hiPSC-CMs were systematically unresponsive to hypertrophic signals such as the α-adrenoceptor (αAR agonist phenylephrine (PE compared to hESC-CMs. We investigated signaling at multiple levels to understand the underlying mechanism of this differential responsiveness. The expression of the normal α1AR gene, ADRA1A, was reversibly silenced during differentiation, accompanied by ADRA1B upregulation in either cell type. ADRA1B signaling was intact in hESC-CMs, but not in hiPSC-CMs. We observed an increased tonic activity of inhibitory kinase pathways in hiPSC-CMs, and inhibition of antihypertrophic kinases revealed hypertrophic increases. There is tonic suppression of cell growth in hiPSC-CMs, but not hESC-CMs, limiting their use in investigation of hypertrophic signaling. These data raise questions regarding the hiPSC-CM as a valid model for certain aspects of cardiac disease.

  7. Increasing thyroid-stimulating hormone is associated with impaired glucose metabolism in euthyroid obese children and adolescents.

    Science.gov (United States)

    Radhakishun, Nalini N E; van Vliet, Mariska; von Rosenstiel, Ines A; Weijer, Olivier; Beijnen, Jos H; Brandjes, Dees P M; Diamant, Michaela

    2013-01-01

    Contrasting data exist regarding the relationship between thyroid-stimulating hormone (TSH) and obesity-related risk factors in children. In the present study, we investigated the association between TSH, free T4 (fT4) and cardiometabolic risk factors in euthyroid obese children and adolescents. A retrospective analysis of patient records was performed on data from 703 multi-ethnic obese children and adolescents who visited an obesity-outpatient clinic. We performed anthropometric measurements, an oral glucose tolerance test, and measured serum TSH, fT4 and lipid levels. A positive association between TSH and the standard deviation score of the body mass index (BMI-Z) was found. After adjustment for ethnicity, sex, pubertal stage and BMI-Z, logistic regression analysis showed significant associations between TSH levels and impaired fasting glucose, impaired glucose tolerance, high total cholesterol, high low-density lipoprotein cholesterol and high triglycerides. No significant associations between fT4 levels and cardiometabolic risk factors were found in linear/logistic regression analysis. In our multi-ethnic cohort of euthyroid obese children and adolescents increasing TSH was associated with impaired glucose metabolism and dyslipidemia.

  8. TNF-alpha stimulation increases dental pulp stem cell migration in vitro through integrin alpha-6 subunit upregulation.

    Science.gov (United States)

    Shi, Lei; Fu, Shanqi; Fahim, Sidra; Pan, Shuang; Lina, He; Mu, Xiaodan; Niu, Yumei

    2017-03-01

    The dissemination of stem cells into tissues requiring inflammatory and reparative response is fundamentally dependent upon their chemotactic migration. Expression of TNF-α is up regulated in inflamed pulps. Dental pulp cells are also known to express integrin α6 subunit. Expression of integrin subunit α6 has been linked to the acquisition of migratory potential in a wide variety of cell types in both pathological and physiological capacities. Therefore, in this study we examined the effects of a pleiotropic cytokine TNF-α on the migration of hDPSCs and investigated its relationship with expression of integrin α6 in hDPSCs during chemotactic migration. hDPSC cultures were established. Protein expression profile of α6 integrin subunit was determined. Effect of exogenous TNF-α (50ng/mL) on hDPSCs' migration potential was evaluated by transwell inserts and in vitro scratch assay. Upregulation/downregulation of TNF-α mediated migration was assayed in presence/absence of integrin α6 respectively. To suppress integrin α6 expression, cells were transfected with integrin α6 siRNA and then cell migration and cytoskeletal changes were evaluated. Our results showed significant increase of hDPSCs' migration after stimulation with TNF-α. By knockdown of integrin α6, which is upregulated by TNF-α, we observed a decrease in the TNF-α directed chemotaxis of hDPSCs. In this study, we show that activation of integrin α6 brought about by TNF-α led to an increase in migratory activity in DPSCs in vitro thus describing a novel association between a cytokine TNF-α and α6 chain of an adhesion receptor integrin in regulating migration of hDPSCs. Copyright © 2016. Published by Elsevier Ltd.

  9. Carbonic Anhydrase I, II, and VI, Blood Plasma, Erythrocyte and Saliva Zinc and Copper Increase After Repetitive Transcranial Magnetic Stimulation

    Science.gov (United States)

    Henkin, Robert I.; Potolicchio, Samuel J.; Levy, Lucien M.; Moharram, Ramy; Velicu, Irina; Martin, Brian M.

    2010-01-01

    Introduction Repetitive transcranial magnetic stimulation (rTMS) has been used to treat symptoms from many disorders; biochemical changes occurred with this treatment. Preliminary studies with rTMS in patients with taste and smell dysfunction improved sensory function and increased salivary carbonic anhydrase (CA) VI and erythrocyte CA I, II. To obtain more information about these changes after rTMS, we measured changes in several CA enzymes, proteins, and trace metals in their blood plasma, erythrocytes, and saliva. Methods Ninety-three patients with taste and smell dysfunction were studied before and after rTMS in an open clinical trial. Before and after rTMS, we measured erythrocyte CA I, II and salivary CA VI, zinc and copper in parotid saliva, blood plasma, and erythrocytes, and appearance of novel salivary proteins by using mass spectrometry. Results After rTMS, CA I, II and CA VI activity and zinc and copper in saliva, plasma, and erythrocytes increased with significant sensory benefit. Novel salivary proteins were induced at an m/z value of 21.5K with a repetitive pattern at intervals of 5K m/z. Conclusions rTMS induced biochemical changes in specific enzymatic activities, trace metal concentrations, and induction of novel salivary proteins, with sensory improvement in patients with taste and smell dysfunction. Because patients with several neurologic disorders exhibit taste and smell dysfunction, including Parkinson disease, Alzheimer disease, and multiple sclerosis, and because rTMS improved their clinical symptoms, the biochemical changes we observed may be relevant not only in our patients with taste and smell dysfunction but also in patients with neurologic disorders with these sensory abnormalities. PMID:20090508

  10. Hypertrophic Effects of Concentric vs. Eccentric Muscle Actions: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Schoenfeld, Brad J; Ogborn, Dan I; Vigotsky, Andrew D; Franchi, Martino V; Krieger, James W

    2017-09-01

    Schoenfeld, BJ, Ogborn, DI, Vigotsky, AD, Franchi, MV, and Krieger, JW. Hypertrophic effects of concentric vs. eccentric muscle actions: A systematic review and meta-analysis. J Strength Cond Res 31(9): 2599-2608, 2017-Controversy exists as to whether different dynamic muscle actions produce divergent hypertrophic responses. The purpose of this paper was to conduct a systematic review and meta-analysis of randomized controlled trials comparing the hypertrophic effects of concentric vs. eccentric training in healthy adults after regimented resistance training (RT). Studies were deemed eligible for inclusion if they met the following criteria: (a) were an experimental trial published in an English-language refereed journal; (b) directly compared concentric and eccentric actions without the use of external implements (i.e., blood pressure cuffs) and all other RT variables equivalent; (c) measured morphologic changes using biopsy, imaging (magnetic resonance imaging, computerized tomography, or ultrasound), bioelectrical impedance, and/or densitometry; (d) had a minimum duration of 6 weeks; and (e) used human participants without musculoskeletal injury or any health condition that could directly, or through the medications associated with the management of said condition, be expected to impact the hypertrophic response to resistance exercise. A systematic literature search determined that 15 studies met inclusion criteria. Results showed that eccentric muscle actions resulted in a greater effect size (ES) compared with concentric actions, but results did not reach statistical significance (ES difference = 0.25 ± 0.13; 95% confidence interval: -0.03 to 0.52; p = 0.076). The mean percent change in muscle growth across studies favored eccentric compared with concentric actions (10.0% vs. 6.8, respectively). The findings indicate the importance of including eccentric and concentric actions in a hypertrophy-oriented RT program, as both have shown to be effective in

  11. The PI3K pathway regulates endochondral bone growth through control of hypertrophic chondrocyte differentiation

    Directory of Open Access Journals (Sweden)

    Beier Frank

    2008-04-01

    Full Text Available Abstract Background The majority of our bones develop through the process of endochondral ossification that involves chondrocyte proliferation and hypertrophic differentiation in the cartilage growth plate. A large number of growth factors and hormones have been implicated in the regulation of growth plate biology, however, less is known about the intracellular signaling pathways involved. PI3K/Akt has been identified as a major regulator of cellular proliferation, differentiation and death in multiple cell types. Results and Discussion Employing an organ culture system of embryonic mouse tibiae and LY294002, a pharmacological inhibitor of PI3K, we show that inhibition of the pathway results in significant growth reduction, demonstrating that PI3K is required for normal endochondral bone growth in vitro. PI3K inhibition reduces the length of the proliferating and particularly of the hypertrophic zone. Studies with organ cultures and primary chondrocytes in micromass culture show delayed hypertrophic differentiation of chondrocytes and increased apoptosis in the presence of LY294002. Surprisingly, PI3K inhibition had no strong effect on IGF1-induced bone growth, but partially blocked the anabolic effects of C-type natriuretic peptide. Conclusion Our data demonstrate an essential role of PI3K signaling in chondrocyte differentiation and as a consequence of this, in the endochondral bone growth process.

  12. The follow-up of progressive hypertrophic cardiomyopathy using magnetic resonance rotating frame relaxation times.

    Science.gov (United States)

    Khan, Muhammad Arsalan; Laakso, Hanne; Laidinen, Svetlana; Kettunen, Sanna; Heikura, Tommi; Ylä-Herttuala, Seppo; Liimatainen, Timo

    2017-12-15

    Magnetic resonance rotating frame relaxation times are an alternative non-contrast agent choice for the diagnosis of chronic myocardial infarct. Fibrosis typically occurs in progressive hypertrophic cardiomyopathy. Fibrosis has been imaged in myocardial infarcted tissue using rotating frame relaxation times, which provides the possibility to follow up progressive cardiomyopathy without contrast agents. Mild and severe left ventricular hypertrophy were induced in mice by transverse aortic constriction, and the longitudinal rotating frame relaxation times (T1ρ ) and relaxation along the fictitious field (TRAFF2 , TRAFF3 ) were measured at 5, 10, 24, 62 and 89 days after transverse aortic constriction in vivo. Myocardial fibrosis was verified using Masson's trichrome staining. Increases in the relative relaxation time differences of T1ρ , together with TRAFF2 and TRAFF3 , between fibrotic and remote tissues over time were observed. Furthermore, TRAFF2 and TRAFF3 showed higher relaxation times overall in fibrotic tissue than T1ρ . Relaxation time differences were highly correlated with an excess of histologically verified fibrosis. We found that TRAFF2 and TRAFF3 are more sensitive than T1ρ to hypertrophic cardiomyopathy-related tissue changes and can serve as non-invasive diagnostic magnetic resonance imaging markers to follow up the mouse model of progressive hypertrophic cardiomyopathy. Copyright © 2017 John Wiley & Sons, Ltd.

  13. Mechanical stimulation of C2C12 cells increases m-calpain expression, focal adhesion plaque protein degradation and cell differentiation

    DEFF Research Database (Denmark)

    Grossi, Alberto; Lawson, Moira Ann

    have shown that m-calpain is necessary for myoblast fusion leading to the formation of muscle fibers and that inhibition of this enzyme restricts myotube formation. Whether there is a link between stretchor load induced signaling and m-calpain expression and activation is not known. Using a magnetic...... documented and has been shown to affect transcription of specific gene sequences, protein synthesis, the immune system and increase in Ca2+ influx. The past 10 years has seen a dramatic increase in the understanding of how proteolytic enzymes such as calpains can affect the growth of muscle. In vivo studies...... bead stimulation assay and a C2C12 mouse myoblast cell population, we have found that mechanical stimulation via laminin receptors leads to an increase in m-calpain expression, an enzyme found to be required for muscle cell fusion. After a short period of stimulation, m-calpain relocates into focal...

  14. Moderate (20%) fructose-enriched diet stimulates salt-sensitive hypertension with increased salt retention and decreased renal nitric oxide.

    Science.gov (United States)

    Gordish, Kevin L; Kassem, Kamal M; Ortiz, Pablo A; Beierwaltes, William H

    2017-04-01

    Previously, we reported that 20% fructose diet causes salt-sensitive hypertension. In this study, we hypothesized that a high salt diet supplemented with 20% fructose (in drinking water) stimulates salt-sensitive hypertension by increasing salt retention through decreasing renal nitric oxide. Rats in metabolic cages consumed normal rat chow for 5 days (baseline), then either: (1) normal salt for 2 weeks, (2) 20% fructose in drinking water for 2 weeks, (3) 20% fructose for 1 week, then fructose + high salt (4% NaCl) for 1 week, (4) normal chow for 1 week, then high salt for 1 week, (5) 20% glucose for 1 week, then glucose + high salt for 1 week. Blood pressure, sodium excretion, and cumulative sodium balance were measured. Systolic blood pressure was unchanged by 20% fructose or high salt diet. 20% fructose + high salt increased systolic blood pressure from 125 ± 1 to 140 ± 2 mmHg (P salt than either high salt, or glucose + high salt (114.2 ± 4.4 vs. 103.6 ± 2.2 and 98.6 ± 5.6 mEq/Day19; P salt group compared to high salt only: 5.33 ± 0.21 versus 7.67 ± 0.31 mmol/24 h; P salt-fed rats, but reduced by 40% in the 20% fructose + high salt group (2139 ± 178 μmol /24 hrs P salt-sensitivity and, combined with a high salt diet, leads to sodium retention, increased blood pressure, and impaired renal nitric oxide availability. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  15. Increased saturated fatty acids in obesity alter resolution of inflammation in part by stimulating prostaglandin production1

    Science.gov (United States)

    Hellmann, Jason; Zhang, Michael J.; Tang, Yunan; Rane, Madhavi; Bhatnagar, Aruni; Spite, Matthew

    2013-01-01

    Extensive evidence indicates that nutrient excess associated with obesity and type 2 diabetes activates innate immune responses that lead to chronic, sterile low-grade inflammation and obese and diabetic humans also have deficits in wound healing and increased susceptibility to infections. Nevertheless, the mechanisms that sustain un-resolved inflammation during obesity remain unclear. Here, we report that saturated free fatty acids that are elevated in obesity alter resolution of acute sterile inflammation by promoting neutrophil survival and decreasing macrophage phagocytosis. Using a targeted mass spectrometry-based lipidomics approach, we found that in db/db mice, prostaglandin (E2/D2) levels were elevated in inflammatory exudates during the development of acute peritonitis. Moreover, in isolated macrophages, palmitic acid stimulated COX-2 induction and prostanoid production. Defects in macrophage phagocytosis induced by palmitic acid were mimicked by PGE2 and PGD2 and were reversed by cyclooxygenase inhibition or prostanoid receptor antagonism. Macrophages isolated from obese-diabetic mice expressed prostanoid receptors, EP2 and DP1, and contained significantly higher levels of downstream effector, cAMP, compared with WT mice. Therapeutic administration of EP2/DP1 dual receptor antagonist, AH6809, decreased neutrophil accumulation in the peritoneum of db/db mice, as well as the accumulation of apoptotic cells in the thymus. Together, these studies provide new insights into the mechanisms underlying altered innate immune responses in obesity and suggest that targeting specific prostanoid receptors may represent a novel strategy for resolving inflammation and restoring phagocyte defects in obese and diabetic individuals. PMID:23785121

  16. Comparison among patients with hypertrophic cardiomyopathy, hypertrophic cardiomyopathy with hypertension and hypertensive heart disease by {sup 123}I-BMIPP myocardial scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Yoneyama, Satoshi; Sugihara, Hiroki; Ito, Kazuki [Kyoto Prefectural Univ. of Medicine (Japan)] [and others

    1997-12-01

    The usefulness of {sup 123}I-BMIPP myocardial SPECT in discriminating hypertrophic cardiomyopathy (46 patients), hypertrophic cardiomyopathy with hypertension (23 patients), and hypertensive hypertrophic heart (20 patients) was studied. SPECT image was divided into 17 domains, and dimension of decreased accumulation was decided visually at each domain as four classes called defect score (DS). Summation of DS (TDS) of each group was used to compare frequency and dimension of decreased accumulation, and characteristic of each site. Frequency of decreased accumulation and TDS in hypertrophic cardiomyopathy were similar in dimension with those in hypertrophic cardiomyopathy with hypertension, and those data in hypertensive hypertrophic heart were lower than those in above-mentioned 2 groups. In the cases of hypertrophic cardiomyopathy and hypertrophic cardiomyopathy with hypertension, decreased accumulation site was similar and was anterior wall-septum junction, septum-posterior wall junction and apex of heart. In the case of hypertensive hypertrophic heart, decreased accumulation site was only the posterior wall. Frequency, dimension and site of decreased accumulation in hypertrophic cardiomyopathy were different from those in hypertensive hypertrophic heart, and BMIPP was thought to be useful in discriminating these diseases. (K.H.)

  17. Keloids and Hypertrophic Scars: Pathophysiology, Classification, and Treatment.

    Science.gov (United States)

    Berman, Brian; Maderal, Andrea; Raphael, Brian

    2017-01-01

    Keloid and hypertrophic scars represent an aberrant response to the wound healing process. These scars are characterized by dysregulated growth with excessive collagen formation, and can be cosmetically and functionally disruptive to patients. Objectives are to describe the pathophysiology of keloid and hypertrophic scar, and to compare differences with the normal wound healing process. The classification of keloids and hypertrophic scars are then discussed. Finally, various treatment options including prevention, conventional therapies, surgical therapies, and adjuvant therapies are described in detail. Literature review was performed identifying relevant publications pertaining to the pathophysiology, classification, and treatment of keloid and hypertrophic scars. Though the pathophysiology of keloid and hypertrophic scars is not completely known, various cytokines have been implicated, including interleukin (IL)-6, IL-8, and IL-10, as well as various growth factors including transforming growth factor-beta and platelet-derived growth factor. Numerous treatments have been studied for keloid and hypertrophic scars,which include conventional therapies such as occlusive dressings, compression therapy, and steroids; surgical therapies such as excision and cryosurgery; and adjuvant and emerging therapies including radiation therapy, interferon, 5-fluorouracil, imiquimod, tacrolimus, sirolimus, bleomycin, doxorubicin, transforming growth factor-beta, epidermal growth factor, verapamil, retinoic acid, tamoxifen, botulinum toxin A, onion extract, silicone-based camouflage, hydrogel scaffold, and skin tension offloading device. Keloid and hypertrophic scars remain a challenging condition, with potential cosmetic and functional consequences to patients. Several therapies exist which function through different mechanisms. Better understanding into the pathogenesis will allow for development of newer and more targeted therapies in the future.

  18. Electrical Stimulation of Low-Threshold Proprioceptive Fibers in the Adult Rat Increases Density of Glutamatergic and Cholinergic Terminals on Ankle Extensor α-Motoneurons.

    Directory of Open Access Journals (Sweden)

    Olga Gajewska-Woźniak

    Full Text Available The effects of stimulation of low-threshold proprioceptive afferents in the tibial nerve on two types of excitatory inputs to α-motoneurons were tested. The first input is formed by glutamatergic Ia sensory afferents contacting monosynaptically α-motoneurons. The second one is the cholinergic input originating from V0c-interneurons, located in lamina X of the spinal cord, modulating activity of α-motoneurons via C-terminals. Our aim was to clarify whether enhancement of signaling to ankle extensor α-motoneurons, via direct electrical stimulation addressed predominantly to low-threshold proprioceptive fibers in the tibial nerve of awake rats, will affect Ia glutamatergic and cholinergic innervation of α-motoneurons of lateral gastrocnemius (LG. LG motoneurons were identified with True Blue tracer injected intramuscularly. Tibial nerve was stimulated for 7 days with continuous bursts of three pulses applied in four 20 min sessions daily. The Hoffmann reflex and motor responses recorded from the soleus muscle, LG synergist, allowed controlling stimulation. Ia terminals and C-terminals abutting on LG-labeled α-motoneurons were detected by immunofluorescence (IF using input-specific anti- VGLUT1 and anti-VAChT antibodies, respectively. Quantitative analysis of confocal images revealed that the number of VGLUT1 IF and VAChT IF terminals contacting the soma of LG α-motoneurons increased after stimulation by 35% and by 26%, respectively, comparing to the sham-stimulated side. The aggregate volume of VGLUT1 IF and VAChT IF terminals increased by 35% and by 30%, respectively. Labeling intensity of boutons was also increased, suggesting an increase of signaling to LG α-motoneurons after stimulation. To conclude, one week of continuous burst stimulation of proprioceptive input to LG α-motoneurons is effective in enrichment of their direct glutamatergic but also indirect cholinergic inputs. The effectiveness of such and longer stimulation in models

  19. Diastolic filling in a physical model of obstructive hypertrophic cardiomyopathy

    Science.gov (United States)

    Schovanec, Joseph; Samaee, Milad; Lai, Hong Kuan; Santhanakrishnan, Arvind

    2015-11-01

    Hypertrophic Cardiomyopathy (HCM) is an inherited heart disease that affects as much as one in 500 individuals, and is the most common cause of sudden death in young athletes. The myocardium becomes abnormally thick in HCM and deforms the internal geometry of the left ventricle (LV). Previous studies have shown that a vortex is formed during diastolic filling, and further that the dilated LV morphology seen in systolic heart failure results in altering the filling vortex from elliptical to spherical shape. We have also previously shown that increasing LV wall stiffness decreases the filling vortex circulation. However, alterations to intraventricular filling fluid dynamics due to an obstructive LV morphology and locally elevated wall stiffness (in the hypertrophied region) have not been previously examined from a mechanistic standpoint. We conducted an experimental study using an idealized HCM physical model and compared the intraventricular flow fields obtained from 2D PIV to a baseline LV physical model with lower wall stiffness and anatomical geometry. The obstruction in the HCM model leads to earlier breakdown of the filling vortex as compared to the anatomical LV. Intraventricular filling in both models under increased heart rates will be discussed.

  20. Hypertrophic osteoarthropathy associated with metastatic melanoma.

    Science.gov (United States)

    Thompson, Michael A; Warner, Noranna B; Hwu, Wen-Jen

    2005-12-01

    Hypertrophic osteoarthropathy (HOA) is one of the paraneoplastic syndromes most commonly associated with non-small-cell lung cancer. Although pulmonary metastasis is the second most common initial site of melanoma metastasis, HOA is rarely detected in patients with metastatic melanoma in the lung. We report a case of a 45-year-old woman with advanced melanoma who developed HOA after her disease had progressed through first-line systemic therapy. The patient's diagnosis of HOA was made on the basis of digital clubbing, arthralgia, pain, joint effusion and periosteal bone formation on X-ray with negative rheumatologic laboratory studies. Only six cases of HOA in metastatic melanoma have been reported previously. This diagnosis should be considered with lung metastases and the presentation of polyarthralgia with appropriate laboratory and imaging findings. Interestingly, the patient responded to bisphosphonates and second-line chemotherapy with carboplatin and paclitaxel, which is commonly used for lung cancer, not advanced melanoma. As with many paraneoplastic syndromes, successful treatment of the underlying disease was associated with a rapid resolution of the symptoms.

  1. A One Health Approach to Hypertrophic Cardiomyopathy

    Science.gov (United States)

    Ueda, Yu; Stern, Joshua A.

    2017-01-01

    Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease in humans and results in significant morbidity and mortality. Research over the past 25 years has contributed enormous insight into this inherited disease particularly in the areas of genetics, molecular mechanisms, and pathophysiology. Our understanding continues to be limited by the heterogeneity of clinical presentations with various genetic mutations associated with HCM. Transgenic mouse models have been utilized especially studying the genotypic and phenotypic interactions. However, mice possess intrinsic cardiac and hemodynamic differences compared to humans and have limitations preventing their direct translation. Other animal models of HCM have been studied or generated in part to overcome these limitations. HCM in cats shows strikingly similar molecular, histopathological, and genetic similarities to human HCM, and offers an important translational opportunity for the study of this disease. Recently, inherited left ventricular hypertrophy in rhesus macaques was identified and collaborative investigations have been conducted to begin to develop a non-human primate HCM model. These naturally-occurring large-animal models may aid in advancing our understanding of HCM and developing novel therapeutic approaches to this disease. This review will highlight the features of HCM in humans and the relevant available and developing animal models of this condition. PMID:28955182

  2. MR imaging findings of hypertrophic olivary degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Do Joong; Jeon, Pyung; Kim, Dong Ik [Yonsei Univ. College of Medicine, Seoul (Korea, Republic of)

    1997-06-01

    To describe the magnetic resonance (MR) imaging findings of hypertrophic olivary degeneration (HOD) MR images of seven patients with HOD were retrospectively reviewed. Two were women and five were men, and they were aged between 48 and 65 (mean 58) years. Imaging examinations were performed with a 1.5-T unit, and the findings were used to evaluate the size and signal intensity of olivary lesions. The time interval from hemorrhagic ictus to MR imaging was between two and 30 months. Follow-up examinations were performed in two patients. All four patients with hemorrhages involving the central tegmental tract in the pons or midbrain showed ipsilateral HOD. Among these four, bilateral HOD was seen in one patient with hemorrhage involving the bilateral central tegmental tract, and in another with tegmental hemorrhage extending to the ipsilateral superior cerebellar peduncle. One patient with cerebellar hemorrhage involving the dentate nucleus had contralateral HOD. Two patients with multiple hemorrhages involving both the pons and cerebellum showed bilateral HOD. Axial MR images showed mild enlargement of the involved olivary mucleus, with high signal intensity on both proton density and T2 weighted images. There was no apparent enhancement on postcontrast T1-weighted images. MR imaging can clearly distinguish secondary olivary degeneration from underlying pathology involving the central tegmental tract in the pons or midbrain and cerebellum. These olivary abnormalities should not, however, be mistaken for primary medullary lesions.

  3. Hypertrophic cardiomyopathy in adults: an overview.

    Science.gov (United States)

    Jacobs, Cynthia

    2014-09-01

    To present an overview of clinical issues related to adults with hypertrophic cardiomyopathy (HCM), their presenting symptoms, diagnosis, physical examination findings, treatment, and follow-up care. A comprehensive search of Medline (PubMed) and CINAHL was conducted using the key terms HCM, treatment, diagnosis, sudden cardiac death (SCD), and complications. This search yielded 21 articles used for this article. There were three reference books used for background, diagnosis, and treatment information as well. Although HCM is the most prevalent genetic disorder affecting the heart, it often goes undiagnosed until midlife after patients show symptoms of myocardial remodeling. Adults with cardiomyopathy suffer SCD or adverse events such as stroke and heart failure from HCM. Early diagnosis will prevent SCD, improve quality of life, and slow patient's progression to heart failure. Early recognition of HCM in adults by their primary care providers will improve patients' quality of life and reduce incidence of SCD, heart failure, and stroke. ©2014 American Association of Nurse Practitioners.

  4. Insulin does not stimulate muscle protein synthesis during increased plasma branched-chain amino acids alone but still decreases whole body proteolysis in humans.

    Science.gov (United States)

    Everman, Sarah; Meyer, Christian; Tran, Lee; Hoffman, Nyssa; Carroll, Chad C; Dedmon, William L; Katsanos, Christos S

    2016-10-01

    Insulin stimulates muscle protein synthesis when the levels of total amino acids, or at least the essential amino acids, are at or above their postabsorptive concentrations. Among the essential amino acids, branched-chain amino acids (BCAA) have the primary role in stimulating muscle protein synthesis and are commonly sought alone to stimulate muscle protein synthesis in humans. Fourteen healthy young subjects were studied before and after insulin infusion to examine whether insulin stimulates muscle protein synthesis in relation to the availability of BCAA alone. One half of the subjects were studied in the presence of postabsorptive BCAA concentrations (control) and the other half in the presence of increased plasma BCAA (BCAA). Compared with that prior to the initiation of the insulin infusion, fractional synthesis rate of muscle protein (%/h) did not change (P > 0.05) during insulin in either the control (0.04 ± 0.01 vs 0.05 ± 0.01) or the BCAA (0.05 ± 0.02 vs. 0.05 ± 0.01) experiments. Insulin decreased (P BCAA (0.89 ± 0.07 vs 0.61 ± 0.03) experiments, but the change was not different between the two experiments (P > 0.05). In conclusion, insulin does not stimulate muscle protein synthesis in the presence of increased circulating levels of plasma BCAA alone. Insulin's suppressive effect on proteolysis is observed independently of the levels of circulating plasma BCAA. Copyright © 2016 the American Physiological Society.

  5. A Novel Magnetic Stimulator Increases Experimental Pain Tolerance in Healthy Volunteers : A Double-Blind Sham-Controlled Crossover Study

    NARCIS (Netherlands)

    Kortekaas, R.; van Nierop, L.E.; Baas, V.G.; Konopka, K.H.; Harbers, M.; van der Hoeven, J.H.; van Wijhe, M.; Aleman, A.; Maurits, N.M.

    2013-01-01

    The 'complex neural pulse'(TM) (CNP) is a neuromodulation protocol employing weak pulsed electromagnetic fields (PEMF). A pioneering paper reported an analgesic effect in healthy humans after 30 minutes of CNP-stimulation using three nested whole head coils. We aimed to devise and validate a

  6. Surface membrane CD4 turnover in phorbol ester stimulated T-lymphocytes. Evidence of degradation and increased synthesis

    DEFF Research Database (Denmark)

    Møller, B K; Andresen, B S; Christensen, E I

    1990-01-01

    Down-regulation of surface membrane CD4 (smCD4) in phorbol ester stimulated T-cells resulted from internalization. Internalization (T1/2 = 15 min at 50 ng PMA/ml) was followed by degradation of CD4-bound antibodies. Degradation in unstimulated T-cells was comparatively insignificant. Release...

  7. Chronic stimulation of the subthalamic nucleus increases daily on-time without dyskinesia in advanced Parkinson's disease

    NARCIS (Netherlands)

    Portman, AT; van Laar, T; Staal, MJ; Rutgers, AWF; Journee, HL; Leenders, KL

    2006-01-01

    We assessed the efficacy of chronic stimulation of the subthalamic nucleus (STN-DBS) in 20 patients with Parkinson's disease (PD) by means of clinical assessments and patient diaries 12 months after surgery. STN-DBS reduced the UPDRS part III off-medication score by 33%, and successively improved

  8. Increases in frontostriatal connectivity are associated with response to dorsomedial repetitive transcranial magnetic stimulation in refractory binge/purge behaviors

    Directory of Open Access Journals (Sweden)

    Katharine Dunlop

    2015-01-01

    Conclusions: Enhanced frontostriatal connectivity was associated with responders to dmPFC-rTMS for binge/purge behavior. rTMS caused paradoxical suppression of frontostriatal connectivity in nonresponders. rs-fMRI could prove critical for optimizing stimulation parameters in a future sham-controlled trial of rTMS in disordered eating.

  9. Determination of relative CMRO2 from CBF and BOLD changes: significant increase of oxygen consumption rate during visual stimulation

    DEFF Research Database (Denmark)

    Kim, S.G.; Rostrup, Egill; Larsson, H.B.

    1999-01-01

    be estimated during neural activity using a reference condition obtained with known CMRO2 change. In this work, nine subjects were studied at a magnetic field of 1.5 T; each subject underwent inhalation of a 5% carbon dioxide gas mixture as a reference and two visual stimulation studies. Relative CBF and BOLD...

  10. Deficiency in macrophage-stimulating protein results in spontaneous intestinal inflammation and increased susceptibility toward epithelial damage in zebrafish

    NARCIS (Netherlands)

    Witte, Merlijn; Huitema, Leonie F. A.; Nieuwenhuis, Edward E. S.; Brugman, Sylvia

    2014-01-01

    Abstract Several genome-wide association studies have identified the genes encoding for macrophage-stimulating protein (MSP) and its receptor RON (Recepteur d'Origine Nantais) as possible susceptibility factors in inflammatory bowel disease. While it has been shown that the MSP-RON signaling pathway

  11. Prevalence of hypertrophic cardiomyopathy in highly trained athletes: relevance to pre-participation screening

    National Research Council Canada - National Science Library

    Basavarajaiah, Sandeep; Wilson, Matthew; Whyte, Gregory; Shah, Ajay; McKenna, William; Sharma, Sanjay

    2008-01-01

    This study sought to determine the prevalence of hypertrophic cardiomyopathy (HCM) in elite athletes. Hypertrophic cardiomyopathy is considered to be the most common cause of exercise-related sudden death in young athletes...

  12. HYPERTROPHIC OBSTRUCTIVE CARDIOMYOPATHY AS A SIDE-EFFECT OF DEXAMETHASONE TREATMENT FOR BRONCHOPULMONARY DYSPLASIA

    NARCIS (Netherlands)

    BRAND, PLP; VANLINGEN, RA; BRUS, F; TALSMA, MD; ELZENGA, NJ

    1993-01-01

    We report three infants who developed hypertrophic obstructive cardiomyopathy during dexamethasone treatment for bronchopulmonary dysplasia. In all three infants, echocardiography had ruled out cardiac abnormalities prior to the dexamethasone course. The hypertrophic obstructive cardiomyopathy

  13. Process of Hypertrophic Scar Formation: Expression of Eukaryotic Initiation Factor 6

    OpenAIRE

    Qing-Qing Yang; Si-Si Yang; Jiang-Lin Tan; Gao-Xing Luo; Wei-Feng He; Jun Wu

    2015-01-01

    Background: Hypertrophic scar is one of the most common complications and often causes the disfigurement or deformity in burn or trauma patients. Therapeutic methods on hypertrophic scar treatment have limitations due to the poor understanding of mechanisms of hypertrophic scar formation. To throw light on the molecular mechanism of hypertrophic scar formation will definitely improve the outcome of the treatment. This study aimed to illustrate the negative role of eukaryotic initiation factor...

  14. The diagnosis of hypertrophic cardiomyopathy by cardiovascular magnetic resonance

    Science.gov (United States)

    2012-01-01

    Hypertrophic cardiomyopathy (HCM) is the most common genetic disease of the heart. HCM is characterized by a wide range of clinical expression, ranging from asymptomatic mutation carriers to sudden cardiac death as the first manifestation of the disease. Over 1000 mutations have been identified, classically in genes encoding sarcomeric proteins. Noninvasive imaging is central to the diagnosis of HCM and cardiovascular magnetic resonance (CMR) is increasingly used to characterize morphologic, functional and tissue abnormalities associated with HCM. The purpose of this review is to provide an overview of the clinical, pathological and imaging features relevant to understanding the diagnosis of HCM. The early and overt phenotypic expression of disease that may be identified by CMR is reviewed. Diastolic dysfunction may be an early marker of the disease, present in mutation carriers prior to the development of left ventricular hypertrophy (LVH). Late gadolinium enhancement by CMR is present in approximately 60% of HCM patients with LVH and may provide novel information regarding risk stratification in HCM. It is likely that integrating genetic advances with enhanced phenotypic characterization of HCM with novel CMR techniques will importantly improve our understanding of this complex disease. PMID:22348519

  15. Keloid and Hypertrophic Scar/span>s Are the Result of Chronic Inflammation in the Reticular Dermis

    Science.gov (United States)

    Ogawa, Rei

    2017-01-01

    Keloids and hypertrophic scar/span>s are caused by cutaneous injury and irritation, including trauma, insect bite, burn, surgery, vaccination, skin piercing, acne, folliculitis, chicken pox, and herpes zoster infection. Notably, superficial injuries that do not reach the reticular dermis never cause keloidal and hypertrophic scarring. This suggests that these pathological scar/span>s are due to injury to this skin layer and the subsequent aberrant wound healing therein. The latter is characterized by continuous and histologically localized inflammation. As a result, the reticular layer of keloids and hypertrophic scar/span>s contains inflammatory cells, increased numbers of fibroblasts, newly formed blood vessels, and collagen deposits. Moreover, proinflammatory factors, such as interleukin (IL)-1α, IL-1β, IL-6, and tumor necrosis factor-α are upregulated in keloid tissues, which suggests that, in patients with keloids, proinflammatory genes in the skin are sensitive to trauma. This may promote chronic inflammation, which in turn may cause the invasive growth of keloids. In addition, the upregulation of proinflammatory factors in pathological scar/span>s suggests that, rather than being skin tumors, keloids and hypertrophic scar/span>s are inflammatory disorders of skin, specifically inflammatory disorders of the reticular dermis. Various external and internal post-wounding stimuli may promote reticular inflammation. The nature of these stimuli most likely shapes the characteristics, quantity, and course of keloids and hypertrophic scar/span>s. Specifically, it is likely that the intensity, frequency, and duration of these stimuli determine how quickly the scars appear, the direction and speed of growth, and the intensity of symptoms. These proinflammatory stimuli include a variety of local, systemic, and genetic factors. These observations together suggest that the clinical differences between keloids and hypertrophic scar/span>s merely reflect differences in

  16. 3.0 T magnetic resonance myocardial perfusion imaging for semi-quantitative evaluation of coronary microvascular dysfunction in hypertrophic cardiomyopathy.

    Science.gov (United States)

    Yin, Liang; Xu, Hai-Yan; Zheng, Sui-Sheng; Zhu, Ying; Xiao, Jiang-Xi; Zhou, Wei; Yu, Si-Si; Gong, Liang-Geng

    2017-12-01

    This study aimed to assess coronary microvascular dysfunction (CMD) differences in hypertrophic cardiomyopathy (HCM) patients using cardiac magnetic resonance (CMR) first-pass perfusion and late gadolinium enhancement imaging. Forty-seven patients with HCM and twenty-one healthy volunteers underwent CMR at rest. Imaging protocols included short axis cine, first-pass myocardial perfusion, and late gadolinium enhancement (LGE). Left ventricular end-diastolic wall thickness (EDTH), LGE, time to peak (T peak ), maximal up-slope (Slope max ), and peak signal intensity (SI peak ) were assessed for each myocardial segment. The HCM myocardial segments were grouped by the degree of LGE and hypertrophy. T peak , SI peak , Slope max and EDTH in multiple groups were assessed and compared by ANOVA test/Kruskal-Wallis test. The Spearman correlation test was used to determine the relationships between EDTH, LGE and perfusion parameters (T peak , Slope max and SI peak ). Compared to control group segments, T peak increased while Slope max and SI peak decreased in non-LGE/non-hypertrophic segments and LGE/hypertrophic segments in the HCM group, while T peak increased more significantly in LGE/hypertrophic segments (all p hypertrophic segments of HCM patients, and it may be helpful in the early diagnosis of coronary microvascular dysfunction in HCM. This abnormal perfusion is associated with the severity of myocardial fibrosis and the degree of hypertrophy.

  17. Repeated 6-Hz Corneal Stimulation Progressively Increases FosB/ΔFosB Levels in the Lateral Amygdala and Induces Seizure Generalization to the Hippocampus.

    Directory of Open Access Journals (Sweden)

    Carmela Giordano

    Full Text Available Exposure to repetitive seizures is known to promote convulsions which depend on specific patterns of network activity. We aimed at evaluating the changes in seizure phenotype and neuronal network activation caused by a modified 6-Hz corneal stimulation model of psychomotor seizures. Mice received up to 4 sessions of 6-Hz corneal stimulation with fixed current amplitude of 32 mA and inter-stimulation interval of 72 h. Video-electroencephalography showed that evoked seizures were characterized by a motor component and a non-motor component. Seizures always appeared in frontal cortex, but only at the fourth stimulation they involved the hippocampus, suggesting the establishment of an epileptogenic process. Duration of seizure non-motor component progressively decreased after the second session, whereas convulsive seizures remained unchanged. In addition, a more severe seizure phenotype, consisting of tonic-clonic generalized convulsions, was predominant after the second session. Immunohistochemistry and double immunofluorescence experiments revealed a significant increase in neuronal activity occurring in the lateral amygdala after the fourth session, most likely due to activity of principal cells. These findings indicate a predominant role of amygdala in promoting progressively more severe convulsions as well as the late recruitment of the hippocampus in the seizure spread. We propose that the repeated 6-Hz corneal stimulation model may be used to investigate some mechanisms of epileptogenesis and to test putative antiepileptogenic drugs.

  18. Forkhead box O1 and muscle RING finger 1 protein expression in atrophic and hypertrophic denervated mouse skeletal muscle

    Science.gov (United States)

    2014-01-01

    Background Forkhead box O (FoxO) transcription factors and E3 ubiquitin ligases such as Muscle RING finger 1 (MuRF1) are believed to participate in the regulation of skeletal muscle mass. The function of FoxO transcription factors is regulated by post-translational modifications such as phosphorylation and acetylation. In the present study FoxO1 protein expression, phosphorylation and acetylation as well as MuRF1 protein expression, were examined in atrophic and hypertrophic denervated skeletal muscle. Methods Protein expression, phosphorylation and acetylation were studied semi-quantitatively using Western blots. Muscles studied were 6-days denervated mouse hind-limb muscles (anterior tibial as well as pooled gastrocnemius and soleus muscles, all atrophic), 6-days denervated mouse hemidiaphragm muscles (hypertrophic) and innervated control muscles. Total muscle homogenates were used as well as separated nuclear and cytosolic fractions of innervated and 6-days denervated anterior tibial and hemidiaphragm muscles. Results Expression of FoxO1 and MuRF1 proteins increased 0.3-3.7-fold in all 6-days denervated muscles studied, atrophic as well as hypertrophic. Phosphorylation of FoxO1 at S256 increased about 0.8-1-fold after denervation in pooled gastrocnemius and soleus muscles and in hemidiaphragm but not in unfractionated anterior tibial muscle. A small (0.2-fold) but statistically significant increase in FoxO1 phosphorylation was, however, observed in cytosolic fractions of denervated anterior tibial muscle. A statistically significant increase in FoxO1 acetylation (0.8-fold) was observed only in denervated anterior tibial muscle. Increases in total FoxO1 and in phosphorylated FoxO1 were only seen in cytosolic fractions of denervated atrophic anterior tibial muscle whereas in denervated hypertrophic hemidiaphragm both total FoxO1 and phosphorylated FoxO1 increased in cytosolic as well as in nuclear fractions. MuRF1 protein expression increased in cytosolic as well

  19. Suppressed inflammatory gene expression during human hypertrophic scar compared to normotrophic scar formation

    NARCIS (Netherlands)

    van den Broek, L.J.; van der Veer, W.M.; de Jong, E.H.; Gibbs, S.; Niessen, F.B.

    2015-01-01

    Hypertrophic scar formation is a result of adverse cutaneous wound healing. The pathogenesis of hypertrophic scar formation is still poorly understood. A problem next to the lack of suitable animal models is that often normal skin is compared to hypertrophic scar (HTscar) and not to normotrophic

  20. An unusual ST-segment elevation: apical hypertrophic cardiomyopathy shows the ace up its sleeve.

    Science.gov (United States)

    de Santis, Francesco; Pergolini, Amedeo; Zampi, Giordano; Pero, Gaetano; Pino, Paolo Giuseppe; Minardi, Giovanni

    2013-01-01

    Apical hypertrophic cardiomyopathy is part of the broad clinical and morphologic spectrum of hypertrophic cardiomyopathy. We report a patient with electrocardiographic abnormalities in whom acute coronary syndrome was excluded and apical hypertrophic cardiomyopathy was demonstrated by careful differential diagnosis. Copyright © 2012 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  1. Hypertrophic olivary degeneration and cerebrovascular disease: movement in a triangle.

    Science.gov (United States)

    Santos, Ana Filipa; Rocha, Sofia; Varanda, Sara; Pinho, João; Rodrigues, Margarida; Ramalho Fontes, João; Soares-Fernandes, João; Ferreira, Carla

    2015-02-01

    Hypertrophic olivary degeneration is a rare kind of trans-synaptic degeneration that occurs after lesions of the dentatorubro-olivary pathway. The lesions, commonly unilateral, may result from hemorrhage due to vascular malformation, trauma, surgical intervention or hypertension, tumor, or ischemia. Bilateral cases are extremely rare. This condition is classically associated with development of palatal tremor, but clinical manifestations can include other involuntary movements. We describe 2 cases: unilateral hypertrophic olivary degeneration in a 60-year-old man with contralateral athetosis and neurologic worsening developing several years after a pontine hemorrhage and bilateral hypertrophic olivary degeneration in a 77-year-old woman with development of palatal tremor, probably secondary to pontine ischemic lesions (small vessel disease). Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  2. Hypertrophic scarring: the greatest unmet challenge following burn injury

    Science.gov (United States)

    Finnerty, Celeste C; Jeschke, Marc G; Branski, Ludwik K; Barret, Juan P.; Dziewulski, Peter; Herndon, David N

    2017-01-01

    Summary Improvements in acute burn care have enabled patients to survive massive burns which would have once been fatal. Now up to 70% of patients develop hypertrophic scars following burns. The functional and psychosocial sequelae remain a major rehabilitative challenge, decreasing quality of life and delaying reintegration into society. The current approach is to optimise the healing potential of the burn wound using targeted wound care and surgery in order to minimise the development of hypertrophic scarring. This approach often fails, and modulation of established scar is continued although the optimal indication, timing, and combination of therapies have yet to be established. The need for novel treatments is paramount, and future efforts to improve outcomes and quality of life should include optimisation of wound healing to attenuate or prevent hypertrophic scarring, well-designed trials to confirm treatment efficacy, and further elucidation of molecular mechanisms to allow development of new preventative and therapeutic strategies. PMID:27707499

  3. Hypertrophic cardiomyopathy: Part 1 - Introduction, pathology and pathophysiology

    Directory of Open Access Journals (Sweden)

    Praveen Kerala Varma

    2014-01-01

    Full Text Available Hypertrophic cardiomyopathy (HCM is the most common genetic cardiovascular disease with many genotype and phenotype variations. Earlier terminologies, hypertrophic obstructive cardiomyopathy and idiopathic hypertrophic sub-aortic stenosis are no longer used to describe this entity. Patients present with or without left ventricular outflow tract (LVOT obstruction. Resting or provocative LVOT obstruction occurs in 70% of patients and is the most common cause of heart failure. The pathology and pathophysiology of HCM includes hypertrophy of the left ventricle with or without right ventricular hypertrophy, systolic anterior motion of mitral valve, dynamic and mechanical LVOT obstruction, mitral regurgitation, diastolic dysfunction, myocardial ischemia, and fibrosis. Thorough understanding of pathology and pathophysiology is important for anesthetic and surgical management.

  4. Risk stratification at the time of diagnosis for children with hypertrophic cardiomyopathy: a report from the Pediatric Cardiomyopathy Registry Study Group

    Science.gov (United States)

    Lipshultz, Steven E; Orav, E John; Wilkinson, James D; Towbin, Jeffrey A; Messere, Jane E; Lowe, April M; Sleeper, Lynn A; Cox, Gerald F; Hsu, Daphne T; Canter, Charles E; Hunter, Juanita A; Colan, Steven D

    2014-01-01

    diagnosis. For all hypertrophic cardiomyopathy subgroups, the risk of death or heart transplantation is significantly increased when two or more risk factors are present and also as the number of risk factors increases. Interpretation Among children with hypertrophic cardiomyopathy, the risk of death or heart transplantation is greater for those who present as infants or with inborn errors of metabolism or with mixed hypertrophic and dilated or restrictive cardiomyopathy. Risk stratification by subgroup of cardiomyopathy, by characteristics such as lower weight, congestive heart failure, or abnormal echocardiographic findings, and by the presence of multiple risk factors allows for more informed clinical decision-making and prognosis at the time of diagnosis. PMID:24011547

  5. Equine Chorionic Gonadotropin and Human Chorionic Gonadotropin Stimulation Increase the Number of Luteinized Follicles and the Progesterone Level Compared with Cabergoline Stimulation in Anoestrus Bitches.

    Science.gov (United States)

    Jurczak, A; Domosławska, A; Bukowska, B; Janowski, T

    2016-08-01

    In this study, ovarian morphologies and blood progesterone concentrations following oestrous induction in bitches were examined. Fifty-three clinically healthy anoestrus bitches received cabergoline at a daily dose of 5 μg/kg of body weight per os for 21 days (group I) or subcutaneous equine chorionic gonadotropin at a dose of 20 IU/kg of body weight for five consecutive days with an additional 500 IU s.c. per bitch of human chorionic gonadotropin on the last day of treatment (group II). Twenty bitches that spontaneously displayed oestrous signs were left untreated and served as controls (group III). The induced oestrous rates and ovulation rates in groups I and II were 60.0% vs 64.3% and 86.7% vs 83.3%, respectively. Morphological assessments of the ovarian structures after ovariohysterectomy revealed an increase in the number of luteinized follicles and cysts in group II compared with the two other groups (p cabergoline (I) and control (III) groups were similar and typical of normally cycling bitches. In conclusion, gonadotropin treatment is associated with an increased progesterone level during the periovulatory period that probably originates from luteinized follicles, whereas cabergoline treatment induces cycles with both physiological progesterone concentrations and ovarian morphologies. © 2016 Blackwell Verlag GmbH.

  6. Stimulation of Cortico-Subthalamic Projections Amplifies Resting Motor Circuit Activity and Leads to Increased Locomotion in Dopamine-Depleted Mice

    Directory of Open Access Journals (Sweden)

    Teresa H. Sanders

    2017-09-01

    Full Text Available Deep brain stimulation (DBS of the subthalamic nucleus (STN improves motor function in patients with Parkinson’s disease (PD. STN-DBS enables similar improved motor function, including increased movement speed (reduced bradykinesia, in the 6-OHDA dopamine-depletion mouse model of PD. Previous analyses of electrophysiological recordings from STN and motor cortex (M1 have explored signaling changes that correspond to PD and amelioration of PD symptoms. The most common results show an increase in beta frequency power during ‘off’ states and a reduction in beta during ‘on’ states. Surprisingly, however, few studies have analyzed whole signal measures of amplitude and coherence during stimulation in freely moving subjects. In previous work by the author, specific transfection of layer five motor cortex projections to the STN revealed an axonal network with collaterals reaching to multiple non-dopaminergic subcortical areas of the brain. The large excitatory shift that stimulation of this axonal network could potentially induce inspired the current study’s hypothesis that amplification of excitatory signaling occurs during stimulation of cortico-subthalamic projections. The results show that, in awake mice, (1 the root-mean-square amplitudes of STN and M1 local field potentials (LFPs are significantly decreased ipsilateral to chronic unilateral 6-OHDA lesions, (2 stimulation of cortico-subthalamic projections increases the amplitude of M1- and STN-LFPs, and 3 M1-LFP amplitude correlates strongly with locomotion speed in lesioned mice. Together, these findings demonstrate that bradykinesia-reducing stimulation of cortico-subthalamic projections amplifies both cortical and subcortical motor circuit activity in unilaterally dopamine-depleted mice. Most PD treatments are focused on increasing dopamine in the dorsal striatum. However, in this study, stimulation of layer five cortico-subthalamic glutamatergic axons that do not directly project

  7. Stimulation of Cortico-Subthalamic Projections Amplifies Resting Motor Circuit Activity and Leads to Increased Locomotion in Dopamine-Depleted Mice.

    Science.gov (United States)

    Sanders, Teresa H

    2017-01-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor function in patients with Parkinson's disease (PD). STN-DBS enables similar improved motor function, including increased movement speed (reduced bradykinesia), in the 6-OHDA dopamine-depletion mouse model of PD. Previous analyses of electrophysiological recordings from STN and motor cortex (M1) have explored signaling changes that correspond to PD and amelioration of PD symptoms. The most common results show an increase in beta frequency power during 'off' states and a reduction in beta during 'on' states. Surprisingly, however, few studies have analyzed whole signal measures of amplitude and coherence during stimulation in freely moving subjects. In previous work by the author, specific transfection of layer five motor cortex projections to the STN revealed an axonal network with collaterals reaching to multiple non-dopaminergic subcortical areas of the brain. The large excitatory shift that stimulation of this axonal network could potentially induce inspired the current study's hypothesis that amplification of excitatory signaling occurs during stimulation of cortico-subthalamic projections. The results show that, in awake mice, (1) the root-mean-square amplitudes of STN and M1 local field potentials (LFPs) are significantly decreased ipsilateral to chronic unilateral 6-OHDA lesions, (2) stimulation of cortico-subthalamic projections increases the amplitude of M1- and STN-LFPs, and 3) M1-LFP amplitude correlates strongly with locomotion speed in lesioned mice. Together, these findings demonstrate that bradykinesia-reducing stimulation of cortico-subthalamic projections amplifies both cortical and subcortical motor circuit activity in unilaterally dopamine-depleted mice. Most PD treatments are focused on increasing dopamine in the dorsal striatum. However, in this study, stimulation of layer five cortico-subthalamic glutamatergic axons that do not directly project to dopaminergic neurons

  8. Arginase inhibition reduces interleukin-1β-stimulated vascular smooth muscle cell proliferation by increasing nitric oxide synthase-dependent nitric oxide production

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Jeongyeon; Ryoo, Sungwoo, E-mail: ryoosw08@kangwon.ac.kr

    2013-06-07

    Highlights: •Arginase inhibition suppressed proliferation of IL-1β-stimulated VSMCs in dose-dependent manner. •NO production from IL-1β-induced iNOS expression was augmented by arginase inhibition, reducing VSMC proliferation. •Incubation with cGMP analogues abolished IL-1β-dependent proliferation of VSMCs. -- Abstract: We investigated whether arginase inhibition suppressed interleukin (IL)-1β-stimulated proliferation in vascular smooth muscle cells (VSMCs) and the possible mechanisms involved. IL-1β stimulation increased VSMC proliferation, while the arginase inhibitor BEC and transfection of the antisense (AS) oligonucleotide against arginase I decreased VSMC proliferation and was associated with increased protein content of the cell cycle regulator p21Waf1/Cip1. IL-1β incubation induced inducible nitric oxide synthase (iNOS) mRNA expression and protein levels in a dose-dependent manner, but did not affect arginase I and II expression. Consistent with this data, IL-1β stimulation resulted in increase in NO production that was significantly augmented by arginase inhibition. The specific iNOS inhibitor 1400W abolished IL-1β-mediated NO production and further accentuated IL-1β-stimulated cell proliferation. Incubation with NO donors GSNO and DETA/NO in the presence of IL-1β abolished VSMCs proliferation and increased p21Waf1/Cip1 protein content. Furthermore, incubation with the cGMP analogue 8-Br-cGMP prevented IL-1β-induced VSMCs proliferation. In conclusion, arginase inhibition augmented iNOS-dependent NO production that resulted in suppression of IL-1β-induced VSMCs proliferation in a cGMP-dependent manner.

  9. Hyperglycemia stimulates p62/PKCζ interaction, which mediates NF-κB activation, increased Nox4 expression, and inflammatory cytokine activation in vascular smooth muscle

    Science.gov (United States)

    Xi, Gang; Shen, Xinchun; Wai, Christine; Vilas, Caroline K.; Clemmons, David R.

    2015-01-01

    Hyperglycemia leads to vascular smooth muscle cell (VSMC) dedifferentiation and enhances responses to IGF-I. Prior studies showed that hyperglycemia stimulated NADPH oxidase 4 (Nox4) synthesis, and IGF-I facilitated its recruitment to a signaling complex where it oxidized src, leading to AKT and MAPK activation. To determine the mechanism that led to these changes, we analyzed the roles of p62 (sequestrosome1) and PKCζ. Hyperglycemia induced a 4.9 ± 1.0-fold increase in p62/PKCζ association, and disruption of PKCζ/p62 using a peptide inhibitor or p62 knockdown reduced PKCζ activation (78 ± 6%). 3-Phosphoinoside–dependent protein kinase 1 was also recruited to the p62 complex and directly phosphorylated PKCζ, leading to its activation (3.1 ± 0.4-fold). Subsequently, activated PKCζ phosphorylated p65 rel, which led to increased Nox4 synthesis. Studies in diabetic mice confirmed these findings (6.0 ± 0.4-fold increase in p62/PKCζ) and their disruption of attenuated Nox4 synthesis (76 ± 9% reduction). PKCζ/p62 activation stimulated inflammatory cytokine production and enhanced IGF-I–stimulated VSMC proliferation. These results define the molecular mechanism by which PKCζ is activated in response to hyperglycemia and suggest that this could be a mechanism by which other stimuli such as cytokines or metabolic stress function to stimulate NF-κB activation, thereby altering VSMC sensitivity to IGF-I.—Xi, G., Shen, X., Wai, C., Vilas, C. K., Clemmons, D. R. Hyperglycemia stimulates p62/PKCζ interaction, which mediates NF-κB activation, increased Nox4 expression, and inflammatory cytokine activation in vascular smooth muscle. PMID:26231202

  10. Scar massage for hypertrophic burns scarring-A systematic review.

    Science.gov (United States)

    Ault, P; Plaza, A; Paratz, J

    2017-06-29

    Scar massage is used in burn units globally to improve functional and cosmetic outcomes of hypertrophic scarring following a burn, however, the evidence to support this therapy is unknown. To review the literature and assess the efficacy of scar massage in hypertrophic burn scars. MEDLINE, PubMed, Embase, CINAHL and the Cochrane Library were searched using the key words "burn", "burn injury", "thermal injury" and "scar", "hypertrophic scar" and "massage", "manipulation", "soft tissue mobilisation", "soft tissue manipulation". The articles were scored by the assessors using the Physiotherapy Evidence Database (PEDro) scale and outcome measures on range of motion (ROM), cosmesis (vascularity, pliability, height), pain scores, pruritus, and psychological measures of depression and anxiety were extracted. Eight publications were included in the review with 258 human participants and 15 animal subjects who received scar massage following a thermal injury resulting in hypertrophic scarring. Outcome measures that demonstrated that scar massage was effective included scar thickness as measured with ultrasonography (p=0.001; g=-0.512); depression (Centre for Epidemiologic Studies - Depression [CES-D]) (p=0.031; g=-0.555); pain as measured with Visual Analogue Scale (VAS) (p=0.000; g=-1.133) and scar characteristics including vascularity (p=0.000; g=-1.837), pliability (p=0.000; g=-1.270) and scar height (p=0.000; g=-2.054). Outcome measures that trended towards significance included a decrease in pruritus (p=0.095; g=-1.157). It appears that there is preliminary evidence to suggest that scar massage may be effective to decrease scar height, vascularity, pliability, pain, pruritus and depression in hypertrophic burns scaring. This review reflects the poor quality of evidence and lack of consistent and valid scar assessment tools. Controlled, clinical trials are needed to develop evidence-based guidelines for scar massage in hypertrophic burns scarring. Copyright © 2017

  11. Deep brain stimulation of the mediodorsal thalamic nucleus yields increases in the expression of zif-268 but not c-fos in the frontal cortex.

    Science.gov (United States)

    Ewing, Samuel G; Porr, Bernd; Pratt, Judith A

    2013-09-01

    This study explores the regions activated by deep brain stimulation of the mediodorsal thalamic nucleus through examination of immediate early genes as markers of neuronal activation. Stimulation was delivered unilaterally with constant current 100 μs duration pulses at a frequency of 130 Hz delivered at an amplitude of 200 μA for 3h. Brains were removed, sectioned and radio-labelled for the IEGs zif-268 and c-fos. In anaesthetised rats, deep brain stimulation of mediodorsal thalamic nucleus produced robust increases in the expression of zif-268 but not c-fos localised to regions that are reciprocally connected with the mediodorsal thalamic nucleus, including the prelimbic and orbitofrontal cortices, and the premotor cortex indicating an increase in synaptic activity in these regions. These findings map those brain regions that are persistently, rather than transiently, activated by high frequency electrical stimulation of the mediodorsal thalamic nucleus by a putatively antidromic mechanism which may be relevant to neuropsychiatric disorders such as schizophrenia in which thalamocortical systems are disrupted and in which DBS protocols are being considered. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Propionic acid and butyric acid inhibit lipolysis and de novo lipogenesis and increase insulin-stimulated glucose uptake in primary rat adipocytes.

    Science.gov (United States)

    Heimann, Emilia; Nyman, Margareta; Degerman, Eva

    2015-01-01

    Fermentation of dietary fibers by colonic microbiota generates short-chain fatty acids (SCFAs), e.g., propionic acid and butyric acid, which have been described to have "anti-obesity properties" by ameliorating fasting glycaemia, body weight and insulin tolerance in animal models. In the present study, we therefore investigate if propionic acid and butyric acid have effects on lipolysis, de novo lipogenesis and glucose uptake in primary rat adipocytes. We show that both propionic acid and butyric acid inhibit isoproterenol- and adenosine deaminase-stimulated lipolysis as well as isoproterenol-stimulated lipolysis in the presence of a phosphodiesterase (PDE3) inhibitor. In addition, we show that propionic acid and butyric acid inhibit basal and insulin-stimulated de novo lipogenesis, which is associated with increased phosphorylation and thus inhibition of acetyl CoA carboxylase, a rate-limiting enzyme in fatty acid synthesis. Furthermore, we show that propionic acid and butyric acid increase insulin-stimulated glucose uptake. To conclude, our study shows that SCFAs have effects on fat storage and mobilization as well as glucose uptake in rat primary adipocytes. Thus, the SCFAs might contribute to healthier adipocytes and subsequently also to improved energy metabolism with for example less circulating free fatty acids, which is beneficial in the context of obesity and type 2 diabetes.

  13. Increased nuclear tri-iodothyronine binding and thyroid hormone-stimulated glucose consumption in mononuclear blood cells from patients with liver cirrhosis

    DEFF Research Database (Denmark)

    Kvetny, J; Matzen, L

    1991-01-01

    control subjects. Serum T3 was decreased in patients with LC. The MBC of T3 was increased significantly (P less than 0.05) in cells from patients with LC compared with patients with AH and controls, whereas the equilibrium association constants did not differ. Unstimulated glucose consumption was slightly......Nuclear tri-iodothyronine (T3) maximal binding capacity (MBC) and thyroxine- and T3-stimulated cellular oxygen consumption and glucose consumption were examined in mononuclear blood cells from six patients with liver cirrhosis (LC), in six patients with alcoholic hepatitis (AH), and in six healthy...... increased (P less than 0.05) in cells from patients with AH and LC compared with controls. Thyroid hormone-stimulated glucose consumption was significantly (P less than 0.05) increased in cells from patients with LC compared with controls and patients with AH. Unstimulated oxygen consumption did not differ...

  14. TRPC4α and TRPC4β Similarly Affect Neonatal Cardiomyocyte Survival during Chronic GPCR Stimulation.

    Science.gov (United States)

    Kirschmer, Nadine; Bandleon, Sandra; von Ehrlich-Treuenstätt, Viktor; Hartmann, Sonja; Schaaf, Alice; Lamprecht, Anna-Karina; Miranda-Laferte, Erick; Langsenlehner, Tanja; Ritter, Oliver; Eder, Petra

    2016-01-01

    The Transient Receptor Potential Channel Subunit 4 (TRPC4) has been considered as a crucial Ca2+ component in cardiomyocytes promoting structural and functional remodeling in the course of pathological cardiac hypertrophy. TRPC4 assembles as homo or hetero-tetramer in the plasma membrane, allowing a non-selective Na+ and Ca2+ influx. Gαq protein-coupled receptor (GPCR) stimulation is known to increase TRPC4 channel activity and a TRPC4-mediated Ca2+ influx which has been regarded as ideal Ca2+ source for calcineurin and subsequent nuclear factor of activated T-cells (NFAT) activation. Functional properties of TRPC4 are also based on the expression of the TRPC4 splice variants TRPC4α and TRPC4β. Aim of the present study was to analyze cytosolic Ca2+ signals, signaling, hypertrophy and vitality of cardiomyocytes in dependence on the expression level of either TRPC4α or TRPC4β. The analysis of Ca2+ transients in neonatal rat cardiomyocytes (NRCs) showed that TRPC4α and TRPC4β affected Ca2+ cycling in beating cardiomyocytes with both splice variants inducing an elevation of the Ca2+ transient amplitude at baseline and TRPC4β increasing the Ca2+ peak during angiotensin II (Ang II) stimulation. NRCs infected with TRPC4β (Ad-C4β) also responded with a sustained Ca2+ influx when treated with Ang II under non-pacing conditions. Consistent with the Ca2+ data, NRCs infected with TRPC4α (Ad-C4α) showed an elevated calcineurin/NFAT activity and a baseline hypertrophic phenotype but did not further develop hypertrophy during chronic Ang II/phenylephrine stimulation. Down-regulation of endogenous TRPC4α reversed these effects, resulting in less hypertrophy of NRCs at baseline but a markedly increased hypertrophic enlargement after chronic agonist stimulation. Ad-C4β NRCs did not exhibit baseline calcineurin/NFAT activity or hypertrophy but responded with an increased calcineurin/NFAT activity after GPCR stimulation. However, this effect was not translated into an

  15. TRPC4α and TRPC4β Similarly Affect Neonatal Cardiomyocyte Survival during Chronic GPCR Stimulation.

    Directory of Open Access Journals (Sweden)

    Nadine Kirschmer

    Full Text Available The Transient Receptor Potential Channel Subunit 4 (TRPC4 has been considered as a crucial Ca2+ component in cardiomyocytes promoting structural and functional remodeling in the course of pathological cardiac hypertrophy. TRPC4 assembles as homo or hetero-tetramer in the plasma membrane, allowing a non-selective Na+ and Ca2+ influx. Gαq protein-coupled receptor (GPCR stimulation is known to increase TRPC4 channel activity and a TRPC4-mediated Ca2+ influx which has been regarded as ideal Ca2+ source for calcineurin and subsequent nuclear factor of activated T-cells (NFAT activation. Functional properties of TRPC4 are also based on the expression of the TRPC4 splice variants TRPC4α and TRPC4β. Aim of the present study was to analyze cytosolic Ca2+ signals, signaling, hypertrophy and vitality of cardiomyocytes in dependence on the expression level of either TRPC4α or TRPC4β. The analysis of Ca2+ transients in neonatal rat cardiomyocytes (NRCs showed that TRPC4α and TRPC4β affected Ca2+ cycling in beating cardiomyocytes with both splice variants inducing an elevation of the Ca2+ transient amplitude at baseline and TRPC4β increasing the Ca2+ peak during angiotensin II (Ang II stimulation. NRCs infected with TRPC4β (Ad-C4β also responded with a sustained Ca2+ influx when treated with Ang II under non-pacing conditions. Consistent with the Ca2+ data, NRCs infected with TRPC4α (Ad-C4α showed an elevated calcineurin/NFAT activity and a baseline hypertrophic phenotype but did not further develop hypertrophy during chronic Ang II/phenylephrine stimulation. Down-regulation of endogenous TRPC4α reversed these effects, resulting in less hypertrophy of NRCs at baseline but a markedly increased hypertrophic enlargement after chronic agonist stimulation. Ad-C4β NRCs did not exhibit baseline calcineurin/NFAT activity or hypertrophy but responded with an increased calcineurin/NFAT activity after GPCR stimulation. However, this effect was not

  16. Human Articular Cartilage Progenitor Cells Are Responsive to Mechanical Stimulation and Adenoviral-Mediated Overexpression of Bone-Morphogenetic Protein 2.

    Directory of Open Access Journals (Sweden)

    Alexander J Neumann

    Full Text Available Articular cartilage progenitor cells (ACPCs represent a new and potentially powerful alternative cell source to commonly used cell sources for cartilage repair, such as chondrocytes and bone-marrow derived mesenchymal stem cells (MSCs. This is particularly due to the apparent resistance of ACPCs to hypertrophy. The current study opted to investigate whether human ACPCs (hACPCs are responsive towards mechanical stimulation and/or adenoviral-mediated overexpression of bone morphogenetic protein 2 (BMP-2. hACPCs were cultured in fibrin-polyurethane composite scaffolds. Cells were cultured in a defined chondro-permissive medium, lacking exogenous growth factors. Constructs were cultured, for 7 or 28 days, under free-swelling conditions or with the application of complex mechanical stimulation, using a custom built bioreactor that is able to generate joint-like movements. Outcome parameters were quantification of BMP-2 and transforming growth factor beta 1 (TGF-β1 concentration within the cell culture medium, biochemical and gene expression analyses, histology and immunohistochemistry. The application of mechanical stimulation alone resulted in the initiation of chondrogenesis, demonstrating the cells are mechanoresponsive. This was evidenced by increased GAG production, lack of expression of hypertrophic markers and a promising gene expression profile (significant up-regulation of cartilaginous marker genes, specifically collagen type II, accompanied by no increase in the hypertrophic marker collagen type X or the osteogenic marker alkaline phosphatase. To further investigate the resistance of ACPCs to hypertrophy, overexpression of a factor associated with hypertrophic differentiation, BMP-2, was investigated. A novel, three-dimensional, transduction protocol was used to transduce cells with an adenovirus coding for BMP-2. Over-expression of BMP-2, independent of load, led to an increase in markers associated with hypertropy. Taken together ACPCs

  17. Subthalamic Nucleus Deep Brain Stimulation in Early Stage Parkinson’s Disease Is Not Associated with Increased Body Mass Index

    OpenAIRE

    Sarah H. Millan; Mallory L. Hacker; Maxim Turchan; Molinari, Anna L.; Currie, Amanda D.; David Charles

    2017-01-01

    Previous studies suggest that deep brain stimulation of the subthalamic nucleus (STN-DBS) for Parkinson's disease (PD) leads to weight gain. This study analyzes changes in body mass index (BMI) in 29 subjects from a prospective, single-blind trial of DBS in early stage PD (age 50?75, Hoehn & Yahr stage II off medication, treated with antiparkinsonian medications for ?6 months but 0.05). BMI change over two years was not different between the groups (p = 0.62, ODT = ?0.89; DBS+ODT = ?0.17). T...

  18. Determination of relative CMRO2 from CBF and BOLD changes: significant increase of oxygen consumption rate during visual stimulation

    DEFF Research Database (Denmark)

    Kim, S.G.; Rostrup, Egill; Larsson, H.B.

    1999-01-01

    The blood oxygenation level-dependent (BOLD) effect in functional magnetic resonance imaging depends on at least partial uncoupling between cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) changes. By measuring CBF and BOLD simultaneously, the relative change in CMRO2 can...... change of 0.6 +/- 0.4%. Assuming that CMRO2 does not change during hypercapnia and that hemodynamic responses during hypercapnia and neural stimulation are similar, relative CMRO2 change was determined using BOLD biophysical models. The average CMRO2 change in the visual cortex ranged from 15.6 +/- 8...

  19. Maternal hyperthyroidism after intrauterine insemination due to hypertrophic action of human chorionic gonadotropin: a case report.

    Science.gov (United States)

    Bakas, P; Tzouma, C; Creatsa, M; Boutas, I; Hassiakos, D

    2016-01-01

    To report a rare case of maternal hyperthyroidism after intrauterine insemination due to hypertrophic action of hCG. A 36-year-old woman after successful intrauterine insemination and triplet pregnancy, developed hyperthyroidism with resistance to medical treatment. All signs of hyperthyroidism resolved and the results of thyroid function tests returned to normal without any medication after embryo meiosis. De novo maternal hyperthyroidism may develop during pregnancy as a result of pathological stimulation of the thyroid gland from the high levels of hCG hormone that can be seen in multiple pregnancies. The risk of hyperthyroidism is related to the number of fetuses. Reversibility of symptomatology can be seen after fetal reduction of multiple pregnancies.

  20. Selective increase of intention-based economic decisions by noninvasive brain stimulation to the dorsolateral prefrontal cortex.

    Science.gov (United States)

    Nihonsugi, Tsuyoshi; Ihara, Aya; Haruno, Masahiko

    2015-02-25

    The intention behind another's action and the impact of the outcome are major determinants of human economic behavior. It is poorly understood, however, whether the two systems share a core neural computation. Here, we investigated whether the two systems are causally dissociable in the brain by integrating computational modeling, functional magnetic resonance imaging, and transcranial direct current stimulation experiments in a newly developed trust game task. We show not only that right dorsolateral prefrontal cortex (DLPFC) activity is correlated with intention-based economic decisions and that ventral striatum and amygdala activity are correlated with outcome-based decisions, but also that stimulation to the DLPFC selectively enhances intention-based decisions. These findings suggest that the right DLPFC is involved in the implementation of intention-based decisions in the processing of cooperative decisions. This causal dissociation of cortical and subcortical backgrounds may indicate evolutionary and developmental differences in the two decision systems. Copyright © 2015 the authors 0270-6474/15/53412-08$15.00/0.

  1. Alcohol decreases baseline brain glucose metabolism more in heavy drinkers than controls but has no effect on stimulation-induced metabolic increases.

    Science.gov (United States)

    Volkow, Nora D; Wang, Gene-Jack; Shokri Kojori, Ehsan; Fowler, Joanna S; Benveniste, Helene; Tomasi, Dardo

    2015-02-18

    During alcohol intoxication, the human brain increases metabolism of acetate and decreases metabolism of glucose as energy substrate. Here we hypothesized that chronic heavy drinking facilitates this energy substrate shift both for baseline and stimulation conditions. To test this hypothesis, we compared the effects of alcohol intoxication (0.75 g/kg alcohol vs placebo) on brain glucose metabolism during video stimulation (VS) versus when given with no stimulation (NS), in 25 heavy drinkers (HDs) and 23 healthy controls, each of whom underwent four PET-(18)FDG scans. We showed that resting whole-brain glucose metabolism (placebo-NS) was lower in HD than controls (13%, p = 0.04); that alcohol (compared with placebo) decreased metabolism more in HD (20 ± 13%) than controls (9 ± 11%, p = 0.005) and in proportion to daily alcohol consumption (r = 0.36, p = 0.01) but found that alcohol did not reduce the metabolic increases in visual cortex from VS in either group. Instead, VS reduced alcohol-induced decreases in whole-brain glucose metabolism (10 ± 12%) compared with NS in both groups (15 ± 13%, p = 0.04), consistent with stimulation-related glucose metabolism enhancement. These findings corroborate our hypothesis that heavy alcohol consumption facilitates use of alternative energy substrates (i.e., acetate) for resting activity during intoxication, which might persist through early sobriety, but indicate that glucose is still favored as energy substrate during brain stimulation. Our findings are consistent with reduced reliance on glucose as the main energy substrate for resting brain metabolism during intoxication (presumably shifting to acetate or other ketones) and a priming of this shift in HDs, which might make them vulnerable to energy deficits during withdrawal. Copyright © 2015 the authors 0270-6474/15/353248-08$15.00/0.

  2. Diel vertical migration of zooplankton in a hypertrophic shallow ...

    African Journals Online (AJOL)

    Zooplankton as important links in the food web of aquatic ecosystems have been studied extensively. In current literature their diel vertical migration (DVM) is a highly discussed issue. In this investigation DVM by zooplankton is studied in a hypertrophic shallow lake in Germany. The objectives of the study were to see if ...

  3. diel vertical migration of zooplankton in a hypertrophic shallow

    African Journals Online (AJOL)

    Preferred Customer

    ABSTRACT: Zooplankton as important links in the food web of aquatic ecosystems have been studied extensively. In current literature their diel vertical migration (DVM) is a highly discussed issue. In this investigation DVM by zooplankton is studied in a hypertrophic shallow lake in Germany. The objectives of the study were ...

  4. Prognosis in hypertrophic cardiomyopathy observed in a large clinic population

    NARCIS (Netherlands)

    M.J.M. Kofflard (Marcel); D.J. Waldstein; J. Vos (Jeroen); F.J. ten Cate (Folkert)

    1993-01-01

    textabstractOverall annual cardiac mortality in hypertrophic cardiomyopathy (HC) has been reported to be between 2 and 4%, although these numbers are primarily from retrospective studies of patients referred to large research institutions. A clinic population of 113 patients with HC was

  5. Hypertrophic cardiomyopathy in South African Blacks | Lewis | South ...

    African Journals Online (AJOL)

    Hypertrophic cardiomyopathy (HCM) has been considered rare among the Black population of southern Africa. We report 7 patients with the disease who presented during a 14-month period. Current concepts in the approach to the diagnosis and treatment of HCM are discussed. It is possible that with greater awareness of ...

  6. Potential cellular and molecular causes of hypertrophic scar formation

    NARCIS (Netherlands)

    Veer, van der W.M.; Bloemen, M.C.; Ulrich, M.; Molema, G.; Zuijlen, van P.P.; Middelkoop, E.; Niessen, F.B.

    2009-01-01

    A scar is an expected result of wound healing. However, in some individuals, and particularly in burn victims, the wound healing processes may lead to a fibrotic hypertrophic scar, which is raised, red, inflexible and responsible for serious functional and cosmetic problems. It seems that a wide

  7. Potential cellular and molecular causes of hypertrophic scar formation

    NARCIS (Netherlands)

    van der Veer, Willem M.; Bloemen, Monica C. T.; Ulrich, Magda M. W.; Molema, Grietje; van Zuijlen, Paul P.; Middelkoop, Esther; Niessen, Frank B.

    A scar is an expected result of wound healing. However, in some individuals, and particularly in burn victims, the wound healing processes may lead to a fibrotic hypertrophic scar, which is raised, red, inflexible and responsible serious functional and cosmetic problems. It seems that a wide array

  8. A case of idiopathc hypertrophic pachtymeningitis | Minne | SA ...

    African Journals Online (AJOL)

    SA Journal of Radiology. Journal Home · ABOUT · Advanced Search · Current Issue · Archives · Journal Home > Vol 8, No 4 (2004) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register. A case of idiopathc hypertrophic pachtymeningitis. C Minne, N Khan. Abstract.

  9. Infantile hypertrophic pyloric stenosis: A case report | Okafor ...

    African Journals Online (AJOL)

    Background: The frequency of infantile hypertrophic stenosis is not known in Nigeria. The first case coming to our attention is described. Method: Descriptive case report. Results and conclusion: The infant was otherwise well with low birth weight.. A suggestive abdominal ultrasound was confirmed by barium contrast study ...

  10. Bilious Vomiting in Infantile Hypertrophic Pyloric Stenosis | Tan ...

    African Journals Online (AJOL)

    Infantile Hypertrophic Pyloric Stenosis (IHPS) is the most common cause of intestinal obstruction requiring surgery in the newborn. The exact aetiology is unknown. IHPS classically presents with non-bilious vomiting. Bilious vomiting is a rare presentation of IHPS that could lead to confusion in diagnosis. In this report we ...

  11. Gastric emptying in adults treated for infantile hypertrophic pyloric stenosis

    DEFF Research Database (Denmark)

    Rasmussen, L; Oster-Jörgensen, E; Hansen, L P

    1989-01-01

    The gastric emptying rate was scintigraphically determined in 6 women and 26 men who had undergone medical or surgical treatment for infantile hypertrophic pyloric stenosis a median of 29 years previously. Dyspeptic complaints were reported by four of the seven medically treated and nine of the 25...

  12. Orchidectomy Ameliorates the Vascular Hypertrophic Effect of A ...

    African Journals Online (AJOL)

    Dr Olaleye Samuel

    Orchidectomy Ameliorates the Vascular Hypertrophic Effect of A. High Salt Diet in Sprague-Dawley Rats. Oloyo, AK1, Vineetha VP 2 , Anigbogu CN1 and Sofola, OA1. 1Department of Physiology, College of Medicine, University of Lagos. 2Laboratory for Experimental Pathology, Biomedical Technology (BMT) Wing, Sree ...

  13. Hypertrophic Cardiomyopathy in a Middle Aged Man - A Case Report

    African Journals Online (AJOL)

    Recognition of the condition in our environment is often difficult because of dearth of facilities and expertise for echocardiograghy in most of our hospitals. Objective: To draw attention to the existence of hypertrophic cardiomyopathy in our environment and need to use echocardiography in evaluating patients with cardiac ...

  14. Penetrance of Hypertrophic Cardiomyopathy in Children and Adolescents

    DEFF Research Database (Denmark)

    Jensen, Morten K; Havndrup, Ole; Christiansen, Michael

    2013-01-01

    The penetrance of hypertrophic cardiomyopathy (HCM) during childhood and adolescence has been only sparsely described. We studied the penetrance of HCM and the short- and long-term outcomes of clinical screening and predictive genetic testing of child relatives of patients with HCM....

  15. Private mitochondrial DNA variants in danish patients with hypertrophic cardiomyopathy

    DEFF Research Database (Denmark)

    Hagen, Christian M; Aidt, Frederik H; Havndrup, Ole

    2015-01-01

    Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease primarily caused by mutations in genes coding for sarcomeric proteins. A molecular-genetic etiology can be established in ~60% of cases. Evolutionarily conserved mitochondrial DNA (mtDNA) haplogroups are susceptibility factors for HCM...

  16. Founder mutations in hypertrophic cardiomyopathy patients in the Netherlands

    NARCIS (Netherlands)

    Christiaans, I.; Nannenberg, E. A.; Dooijes, D.; Jongbloed, R. J. E.; Michels, M.; Postema, P. G.; Majoor-Krakauer, D.; van den Wijngaard, A.; Mannens, M. M. A. M.; van Tintelen, J. P.; van Langen, I. M.; Wilde, A. A. M.

    In this part of a series on cardiogenetic founder mutations in the Netherlands, we review the Dutch founder mutations in hypertrophic cardiomyopathy (HCM) patients. HCM is a common autosomal dominant genetic disease affecting at least one in 500 persons in the general population. Worldwide, most

  17. Infantile Hypertrophic pyloric stenosis: A retrospective study from a ...

    African Journals Online (AJOL)

    Back ground: Infantile hypertrophic pyloric stenosis(IHPS) is a common infantile disorder characterized by enlarged pyloric musculature and gastric outlet obstruction(1). IHPS typically presents with progressive projectile non-bilious vomiting this usually commences between second and eighth week of age. To date there is ...

  18. Peripheral vascular structure and function in hypertrophic cardiomyopathy

    NARCIS (Netherlands)

    Rowley, N.J.; Green, D.J.; George, K.; Thijssen, D.H.J.; Oxborough, D.; Sharma, S.; Somauroo, J.D.; Jones, J.; Sheikh, N.; Whyte, G.

    2012-01-01

    BACKGROUND: Hypertrophic cardiomyopathy (HCM) is characterised by idiopathic cardiac enlargement and represents the most frequent cause of sudden cardiac death in athletes under the age of 35 years. Differentiation between physiological (ie, exercise-related) and pathological (ie, HCM-related)

  19. Increase in oxytocin and vasopressin concentration in the blood outflowing from sella turcica region after superior cervical ganglion stimulation in rat

    Energy Technology Data Exchange (ETDEWEB)

    Lipinska, S.; Orlowska-Majdak, M.; Traczyk, W.Z. [Akademia Medyczna, Lodz (Poland). Katedra Fizjologii

    1996-12-31

    The aim of the study was to investigate whether the stimulation of the superior cervical ganglion influences the oxytocin and vasopressin release into the blood in condition of the of the sella turcica integrity. The experiments were performed on male rats under urethane-chloralose anaesthesia. Four 0.7 ml samples of the blood from the sella turcica region flowing through a tube inserted in the maxillary interna vein were collected in the 30, 35, 60 and 90 min of the experiments. The animals were divided into three groups: 1) control, 2) after the exposition of superior cervical ganglion. 3) after the collection of the 1-st sample of the blood the superior cervical ganglion was electrically stimulated for 30 min with trains of pulses. Vasopressin (AVP) and oxytocin (OXY) were determined in the blood plasma by radioimmunoassay. Stimulation of the superior cervical ganglion evoked an significant increase of AVP and OXY release into the blood. The increase of AVP release occurred after 30 min longer latency than the increase of OXY release. (author). 32 refs, 2 figs.

  20. Increased Responsiveness to Toll-Like Receptor 4 Stimulation in Peripheral Blood Mononuclear Cells from Patients with Recent Onset Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    M. L. Kowalski

    2008-01-01

    Full Text Available Background. Cell signaling via Toll-like receptors (TLRs leads to synovial inflammation in rheumatoid arthritis (RA. We aimed to assess effects of TLR2 and TLR4 stimulation on proinflammatory cytokine production by peripheral blood mononuclear cells (PBMCs from patients with recent-onset RA, osteoarthrosis (OA, and healthy control (HC. Methods. PBMCs were stimulated with LPS, biglycan and cytokine mix. Cytokines were analyzed in supernatants with ELISA. Expression of toll-like receptors mRNA in leukocytes was analyzed using real-time qPCR. Results. PBMCs from RA patients spontaneously produced less IL-6 and TNFα than cells from OA and HC subjects. LPS increased cytokines' production in all groups. In RA patients increase was dramatic (30 to 48-fold and 17 to 31-fold, for respective cytokines compared to moderate (2 to 8-fold in other groups. LPS induced 15-HETE generation in PBMCs from RA (mean 251% and OA patients (mean 43%, although only in OA group, the increase was significant. TLR2 and TLR4 gene expressions decreased in response to cytokine mix, while LPS enhanced TLR2 expression in HC and depressed TLR4 expression in OA patients. Conclusion. PBMCs from recent-onset RA patients are overresponsive to stimulation with bacterial lipopolysaccharide. TLR expression is differentially regulated in healthy and arthritic subjects.

  1. Co-culture with human synovium-derived mesenchymal stem cells inhibits inflammatory activity and increases cell proliferation of sodium nitroprusside-stimulated chondrocytes

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Jae-Sung; Jung, Yeon-Hwa; Cho, Mi-Young; Yeo, Jee Eun; Choi, Yun-Jin; Kim, Yong Il; Koh, Yong-Gon, E-mail: yonseranglab@daum.net

    2014-05-16

    Highlights: • Co-culture of hSDMSCs with SNP-stimulated chondrocytes improves anti-inflammation. • Co-culture system produces IGF-1. • Co-culture system suppresses inflammatory genes expression. • Co-culture system improves cell proliferation. • Exogenous IGF-1 inhibits inflammatory activity in SNP-stimulated chondrocytes. - Abstract: Rheumatoid arthritis (RA) and osteoarthritis (OA) are primarily chronic inflammatory diseases. Mesenchymal stem cells (MSCs) have the ability to differentiate into cells of the mesodermal lineage, and to regulate immunomodulatory activity. Specifically, MSCs have been shown to secrete insulin-like growth factor 1 (IGF-1). The purpose of the present study was to examine the inhibitory effects on inflammatory activity from a co-culture of human synovium-derived mesenchymal stem cells (hSDMSCs) and sodium nitroprusside (SNP)-stimulated chondrocytes. First, chondrocytes were treated with SNP to generate an in vitro model of RA or OA. Next, the co-culture of hSDMSCs with SNP-stimulated chondrocytes reduced inflammatory cytokine secretion, inhibited expression of inflammation activity-related genes, generated IGF-1 secretion, and increased the chondrocyte proliferation rate. To evaluate the effect of IGF-1 on inhibition of inflammation, chondrocytes pre-treated with IGF-1 were treated with SNP, and then the production of inflammatory cytokines was analyzed. Treatment with IGF-1 was shown to significantly reduce inflammatory cytokine secretion in SNP-stimulated chondrocytes. Our results suggest that hSDMSCs offer a new strategy to promote cell-based cartilage regeneration in RA or OA.

  2. Lipoxin A4 stimulates calcium-activated chloride currents and increases airway surface liquid height in normal and cystic fibrosis airway epithelia.

    LENUS (Irish Health Repository)

    2012-01-01

    Cystic Fibrosis (CF) is a genetic disease characterised by a deficit in epithelial Cl(-) secretion which in the lung leads to airway dehydration and a reduced Airway Surface Liquid (ASL) height. The endogenous lipoxin LXA(4) is a member of the newly identified eicosanoids playing a key role in ending the inflammatory process. Levels of LXA(4) are reported to be decreased in the airways of patients with CF. We have previously shown that in normal human bronchial epithelial cells, LXA(4) produced a rapid and transient increase in intracellular Ca(2+). We have investigated, the effect of LXA(4) on Cl(-) secretion and the functional consequences on ASL generation in bronchial epithelial cells obtained from CF and non-CF patient biopsies and in bronchial epithelial cell lines. We found that LXA(4) stimulated a rapid intracellular Ca(2+) increase in all of the different CF bronchial epithelial cells tested. In non-CF and CF bronchial epithelia, LXA(4) stimulated whole-cell Cl(-) currents which were inhibited by NPPB (calcium-activated Cl(-) channel inhibitor), BAPTA-AM (chelator of intracellular Ca(2+)) but not by CFTRinh-172 (CFTR inhibitor). We found, using confocal imaging, that LXA(4) increased the ASL height in non-CF and in CF airway bronchial epithelia. The LXA(4) effect on ASL height was sensitive to bumetanide, an inhibitor of transepithelial Cl(-) secretion. The LXA(4) stimulation of intracellular Ca(2+), whole-cell Cl(-) currents, conductances and ASL height were inhibited by Boc-2, a specific antagonist of the ALX\\/FPR2 receptor. Our results provide, for the first time, evidence for a novel role of LXA(4) in the stimulation of intracellular Ca(2+) signalling leading to Ca(2+)-activated Cl(-) secretion and enhanced ASL height in non-CF and CF bronchial epithelia.

  3. Progressive seizure aggravation in the repeated 6-Hz corneal stimulation model is accompanied by marked increase in hippocampal p-ERK1/2 immunoreactivity in neurons

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    Carmela Giordano

    2016-12-01

    Full Text Available The 6-Hz corneal stimulation test is used to screen novel antiepileptic molecules to overcome the problem of drug refractoriness. Although recognized as a standard test, it has been evaluated only recently in the attempt to characterize the putative neuronal networks involved in seizures caused by corneal stimulation. In particular, by recording from the CA1 region we previously established that the hippocampus participates to propagation of seizure activity. However, these findings were not corroborated by using markers of neuronal activation such as FosB/ΔFosB antigens. In view of this discrepancy, we performed new experiments to characterize the changes in levels of phosphorylated extracellular signal-regulated kinases1/2 (p-ERK1/2, which are also used as markers of neuronal activation. To this aim, mice underwent corneal stimulation up to three different times, in three sessions separated by an interval of three days. To characterize a group in which seizures could be prevented by pharmacological treatment, we also considered pretreatment with the ghrelin receptor antagonist EP-80317 (330 µg/kg. Control mice were sham-treated. Video electrocorticographic recordings were obtained from mice belonging to each group of treatment. Animals were finally used to characterize the immunoreactivity for FosB/ΔFosB and p-ERK1/2 in the hippocampus. As previously shown, FosB/ΔFosB levels were highly increased throughout the hippocampus by the first induced seizure but, in spite of the progressively increased seizure severity, they were restored to control levels after the third stimulation. At variance, corneal stimulation caused a progressive increase in p-ERK1/2 immunoreactivity all over the hippocampus, especially in CA1, peaking in the third session. Predictably, EP-80317 administration reduced both duration and severity of seizures, prevented the increase in FosB/ΔFosB levels in the first session, and partially counteracted the increase in p-ERK1

  4. Mechanism of Progressive Heart Failure and Significance of Pulmonary Hypertension in Obstructive Hypertrophic Cardiomyopathy.

    Science.gov (United States)

    Covella, Michele; Rowin, Ethan J; Hill, Nicholas S; Preston, Ioana R; Milan, Alberto; Opotowsky, Alexander R; Maron, Barry J; Maron, Martin S; Maron, Bradley A

    2017-04-01

    There are limited data on the prevalence, pathophysiology, and management implications of pulmonary hypertension in patients with obstructive hypertrophic cardiomyopathy and advanced heart failure. To assess the clinical significance of measured cardiopulmonary hemodynamics in hypertrophic cardiomyopathy patients with heart failure, we retrospectively assessed right heart catheterization data in 162 consecutive patients with outflow tract gradients (median [interquartile range], 90 mm Hg [70-110 mm Hg]), 59±11 years old, and 49% men, predominately New York Heart Association class III/IV status. Pulmonary hypertension (mean pulmonary artery pressure, ≥25 mm Hg) was present in 82 patients (51%), including 29 (18%) regarded as moderate-severe (mean pulmonary artery pressure, ≥35 mm Hg) and 28 (34%) also had increased pulmonary vascular resistance >3.0 WU. The pulmonary artery wedge pressure was ≤15 mm Hg in 54%, indicating that left atrial hypertension was absent in a majority of patients. Notably, 9 patients (11%) met hemodynamic criteria for precapillary pulmonary hypertension (mean pulmonary artery pressure, ≥25 mm Hg; pulmonary vascular resistance, >3.0 WU; pulmonary artery wedge pressure, ≤15 mm Hg). Over a median follow-up of 327 days (90-743 days) after surgical myectomy (or alcohol septal ablation), 92% and 95% of patients with or without preoperative pulmonary hypertension, respectively, were asymptomatic or mildly symptomatic. One postoperative death occurred in a 59-year-old woman with acute respiratory failure and mean pulmonary artery pressure of 65 mm Hg. Pulmonary hypertension was common in obstructive hypertrophic cardiomyopathy patients with advanced heart failure. Although possibly a contributor to preoperative heart failure, pulmonary hypertension did not significantly influence clinical and surgical outcome. Notably, a novel patient subgroup was identified with resting invasive hemodynamics consistent with pulmonary

  5. Suppressed inflammatory gene expression during human hypertrophic scar compared to normotrophic scar formation.

    Science.gov (United States)

    van den Broek, Lenie J; van der Veer, Willem M; de Jong, Etty H; Gibbs, Susan; Niessen, Frank B

    2015-08-01

    Hypertrophic scar formation is a result of adverse cutaneous wound healing. The pathogenesis of hypertrophic scar formation is still poorly understood. A problem next to the lack of suitable animal models is that often normal skin is compared to hypertrophic scar (HTscar) and not to normotrophic scar (NTscar) tissue. Another drawback is that often only one time period after wounding is studied, while scar formation is a dynamic process over a period of several months. In this study, we compared the expression of genes involved in inflammation, angiogenesis and extracellular matrix (ECM) formation and also macrophage infiltration in biopsies obtained before and up to 52 weeks after standard surgery in five patients who developed HTscar and six patients who developed NTscar. It was found that HTscar formation coincided with a prolonged decreased expression of inflammatory genes (TNFα, IL-1α, IL-1RN, CCL2, CCL3, CXCL2, CXCR2, C3 and IL-10) and an extended increased expression of ECM-related genes (PLAU, Col3A1, TGFβ3). This coincided with a delayed but prolonged infiltration of macrophages (type 2) in HTscar tissue compared to NTscar tissue. These findings were supported by immunohistochemical localization of proteins coding for select genes named above. Our study emphasizes that human cutaneous wound healing is a dynamic process that is needed to be studied over a period of time rather than a single point of time. Taken together, our results suggest innate immune stimulatory therapies may be a better option for improving scar quality than the currently used anti-inflammatory scar therapies. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Evaluating hypertrophic thyroidectomy scar outcomes after treatment with triamcinolone injections and copper bromide laser therapy.

    Science.gov (United States)

    On, Hye Rang; Lee, Sang Hee; Lee, Yong Sang; Chang, Hang-Seok; Park, CheongSoo; Roh, Mi Ryung

    2015-08-01

    Postoperative hypertrophic scar following thyroidectomy can be a major concern due to its disfiguring appearance. Recently, copper bromide laser (CBL) and intralesional triamcinolone injection (TA ILI) have been used to treat hypertrophic thyroidectomy scars. Data regarding the number of treatment sessions needed to reach a certain endpoint and the prognostic factors that affect treatment duration are unknown. The aim of this study was to evaluate the number of treatment sessions required to reduce VSS score by 50%, which was regarded as the treatment endpoint, and to investigate the factors that influence treatment duration when using CBL and TA ILI. A total of 67 patients were enrolled in this study. Baseline characteristics of the patients including age, sex, body mass index (BMI), distance of the scar from the sternal notch, time of development of the hypertrophic scar, sternocleidomastoid (SCM) muscle prominence, and date of operation were collected on the first visit. They were treated with CBL and TA. The concentration of triamcinolone used was 2.5 mg/ml or 5 mg/ml according to the pliability score of each scar. The mean number of treatment sessions required to achieve the endpoint was 3.85 ± 1.25. Among the variables assessed, location of the scar near the sternal notch (P = 0.020) and patient BMI (P = 0.001) were associated with the increasing number of treatment sessions. In our study cohort, four treatments were required to reduce the VSS of thyroidectomy scars by 50% when using a combination treatment of CBL and low concentration TA ILI. Also, scar location and patient BMI are factors that affect treatment outcome. © 2015 Wiley Periodicals, Inc.

  7. SFRP2 and slug contribute to cellular resistance to apoptosis in hypertrophic scars.

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    Liang Chen

    Full Text Available Hypertrophic scars (HS are skin disorders which occur after wounding and thermal injury. Our previous studies have suggested that secreted frizzled-related protein 2 (SFRP2 is involved in HS formation and that the suppression of SFRP2 promotes apoptosis of hypertrophic scar fibroblasts (HSFBs. However, the mechanisms have not been clarified. Previous studies revealed that Slug expression inhibits cell apoptosis, in vitro and in vivo, and SFRP2 regulates the expression of Slug in cervical cancer cells. In the present study, we quantified differential expression levels of expression of SFRP2 and Slug in HS and normal skin tissues by immunohistochemistry, both of which have important anti-apoptosis roles. Furthermore, a short hairpin RNA approach was adopted to investigate the potential function of SFRP2 and Slug in HSFB apoptosis. Cell apoptosis was detected using fluorescence-activated cell sorting and Caspase-3 activity was assayed by spectrophotometry. This study demonstrates that SFRP2 expression, as well as Slug, is dramatically up-regulated in HS relative to normal skin tissues, and the Slug expression is positively correlated with SFRP2. Slug expression was down-regulated in SFRP2-deficient cells, and the down-regulation of Slug expression increased sensitivity to apoptosis which was induced through a caspase-3-dependent pathway. The infected cells with reduced levels of Slug were tested for the expression of apoptosis-related genes (Bcl-2, Bax and PUMA which were previously identified as Slug targets. Bcl-2 expression was down-regulated in Slug-deficient cells. In conclusion, SFRP2 appears to interact with Slug to affect the apoptosis of hypertrophic scar fibroblasts.

  8. Nonfamilial Hypertrophic Cardiomyopathy: Prevalence, Natural History, and Clinical Implications.

    Science.gov (United States)

    Ingles, Jodie; Burns, Charlotte; Bagnall, Richard D; Lam, Lien; Yeates, Laura; Sarina, Tanya; Puranik, Rajesh; Briffa, Tom; Atherton, John J; Driscoll, Tim; Semsarian, Christopher

    2017-04-01

    Yield of causative variants in hypertrophic cardiomyopathy (HCM) is increased in some probands, suggesting different clinical subgroups of disease occur. We hypothesized that a negative family history and no sarcomere mutations represent a nonfamilial subgroup of HCM. We sought to determine the prevalence, natural history, and potential clinical implications of this nonfamilial subgroup of HCM. Four hundred and thirteen unrelated probands with HCM seen in a specialized HCM center between 2002 and 2015 and genetic testing performed were included in this retrospective cohort study. There were 251 (61%) probands with no reported family history of HCM, including 166 (40% of total) probands with no sarcomere mutation, that is, nonfamilial HCM. Quantified family pedigree data revealed no difference in mean number of first-degree relatives screened between nonfamilial and sarcomere-positive groups. Adjusted predictors of nonfamilial status were older age (odds ratio, 1.04; 95% confidence interval, 1.02-1.06; P =0.0001), male sex (odds ratio, 1.96; 95% confidence interval, 1.11-3.45; P =0.02), hypertension (odds ratio, 2.80; 95% confidence interval, 1.57-5.00; P =0.0005), and nonasymmetric septal morphology (odds ratio, 3.41; 95% confidence interval, 1.64-7.08; P =0.001). They had a less severe clinical course with greater event-free survival from major cardiac events ( P =0.04) compared with sarcomere-positive HCM probands. Genotype prediction scores showed good performance in identifying genotype-positive patients (area under the curve, 0.71-0.75) and, in combination with pedigree characteristics, were further improved. Approximately 40% of HCM probands have a nonfamilial subtype, with later onset and less severe clinical course. We propose a revised clinical pathway for management, highlighting the role of genetic testing, a detailed pedigree, and refined clinical surveillance recommendations for family members. © 2017 American Heart Association, Inc.

  9. Sudden death during empiric amiodarone therapy in symptomatic hypertrophic cardiomyopathy.

    Science.gov (United States)

    Fananapazir, L; Leon, M B; Bonow, R O; Tracy, C M; Cannon, R O; Epstein, S E

    1991-01-15

    Amiodarone is reported to improve symptoms and to prevent sudden death in patients with hypertrophic cardiomyopathy (HC). Amiodarone treatment (loading dose 30 g given over 6 weeks; maintenance dose 400 mg/day) was prospectively evaluated in 50 patients with HC in whom the drug was initiated because of symptoms refractory to conventional drug therapy (calcium antagonists and beta blockers). Twenty-one (42%) patients had ventricular tachycardia (VT) during Holter monitoring. Amiodarone significantly and often markedly improved the patients' New York Heart Association functional class status (from 3.3 to 2.7 at 2 months, p less than 0.001) and treadmill exercise duration (p less than 0.001). Eight patients, however, died (7 suddenly) during a mean follow-up period of 2.2 +/- 1.8 years. Of the 7 sudden deaths, 6 occurred within 5 months of initiation of treatment. The 6-month and 1- and 2-year survival rates were 87, 85 and 80%, respectively. The survival rate of patients with VT was significantly worse than that of patients without VT (61 vs 97% at 2 years; p less than 0.01). Sudden death occurred despite abolition of VT on Holter monitoring. Amiodarone increased left ventricular peak filling rate by radionuclide angiography in 20 of 33 patients (61%) (p less than 0.01). Decrease in peak left ventricular filling rate within 10 days of amiodarone therapy (8 of 33 patients) was associated with subsequent sudden death (p less than 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

  10. A Murine Hypertrophic Cardiomyopathy Model: The DBA/2J Strain.

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    Wenyuan Zhao

    Full Text Available Familial hypertrophic cardiomyopathy (HCM is attributed to mutations in genes that encode for the sarcomere proteins, especially Mybpc3 and Myh7. Genotype-phenotype correlation studies show significant variability in HCM phenotypes among affected individuals with identical causal mutations. Morphological changes and clinical expression of HCM are the result of interactions with modifier genes. With the exceptions of angiotensin converting enzyme, these modifiers have not been identified. Although mouse models have been used to investigate the genetics of many complex diseases, natural murine models for HCM are still lacking. In this study we show that the DBA/2J (D2 strain of mouse has sequence variants in Mybpc3 and Myh7, relative to widely used C57BL/6J (B6 reference strain and the key features of human HCM. Four-month-old of male D2 mice exhibit hallmarks of HCM including increased heart weight and cardiomyocyte size relative to B6 mice, as well as elevated markers for cardiac hypertrophy including β-myosin heavy chain (MHC, atrial natriuretic peptide (ANP, brain natriuretic peptide (BNP, and skeletal muscle alpha actin (α1-actin. Furthermore, cardiac interstitial fibrosis, another feature of HCM, is also evident in the D2 strain, and is accompanied by up-regulation of type I collagen and α-smooth muscle actin (SMA-markers of fibrosis. Of great interest, blood pressure and cardiac function are within the normal range in the D2 strain, demonstrating that cardiac hypertrophy and fibrosis are not secondary to hypertension, myocardial infarction, or heart failure. Because D2 and B6 strains have been used to generate a large family of recombinant inbred strains, the BXD cohort, the D2 model can be effectively exploited for in-depth genetic analysis of HCM susceptibility and modifier screens.

  11. Biventricular / Left Ventricular Pacing in Hypertrophic Obstructive Cardiomyopathy: An Overview

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    Radu Vatasescu, MD

    2012-05-01

    Full Text Available Hypertrophic cardiomyopathy (HCM is an autosomal dominant inherited genetic disease characterized by compensatory pathological left ventricle (LV hypertrophy due to sarcomere dysfunction. In an important proportion of patients with HCM, the site and extent of cardiac hypertrophy results in severe obstruction to LV outflow tract (LVOT, contributing to disabling symptoms and increasing the risk of sudden cardiac death (SCD. In patients with progressive and/or refractory symptoms despite optimal pharmacological treatment, invasive therapies that diminish or abolish LVOT obstruction relieve heart failure-related symptoms, improve quality of life and could be associated with long-term survival similar to that observed in the general population. The gold standard in this respect is surgical septal myectomy, which might be supplementary associated with a reduction in SCD. Percutaneous techniques, particularly alcohol septal ablation (ASA and more recently radiofrequency (RF septal ablation, can achieve LVOT gradient reduction and symptomatic benefit in a large proportion of HOCM patients at the cost of a supposedly limited septal myocardial necrosis and a 10-20% risk of chronic atrioventricular block. After an initial period of enthusiasm, standard DDD pacing failed to show in randomized trials significant LVOT gradient reductions and objective improvement in exercise capacity. However, case reports and recent small pilot studies suggested that atrial synchronous LV or biventricular (biV pacing significantly reduce LVOT obstruction and improve symptoms (acutely as well as long-term in a large proportion of severely symptomatic HOCM patients not suitable to other gradient reduction therapies. Moreover, biV/LV pacing in HOCM seems to be associated with significant LV reverse remodelling.

  12. Local inner ear application of dexamethasone in cochlear implant models is safe for auditory neurons and increases the neuroprotective effect of chronic electrical stimulation.

    Directory of Open Access Journals (Sweden)

    Verena Scheper

    Full Text Available Dexamethasone (DEX can reduce fibrous tissue growth as well as loss of residual hearing which may occur after cochlear implantation. Little is known about the effect of local inner ear DEX treatment on the spiral ganglion neurons (SGN, which are the target of the electrical stimulation with a cochlear implant (CI. Three different clinically relevant strategies of DEX-delivery into the inner ear were used. DEX was either eluted from the electrode carriers' silicone, released from a reservoir by passive diffusion, or actively applied using a pump based system. The effect of the locally applied DEX on SGN density, size and function was evaluated. DEX did not affect the SGN density compared to the relevant control groups. Simultaneously applied with chronic electrical stimulation (ES, DEX increased the neuroprotective effect of ES in the basal region and the hearing threshold tended to decrease. The EABR thresholds did not correlate with the relevant SGN density. When correlating the SGN number with fibrosis, no dependency was observed. DEX concentrations as applied in these animal models are safe for inner ear delivery in terms of their effect on SGN density. Additionally, DEX tends to improve the neuroprotective effect of chronic electrical stimulation by increasing the number of surviving neurons. This is an important finding in regard to clinical applications of DEX for local treatment of the inner ear in view of cochlear implantation and other applications.

  13. Local inner ear application of dexamethasone in cochlear implant models is safe for auditory neurons and increases the neuroprotective effect of chronic electrical stimulation.

    Science.gov (United States)

    Scheper, Verena; Hessler, Roland; Hütten, Mareike; Wilk, Maciej; Jolly, Claude; Lenarz, Thomas; Paasche, Gerrit

    2017-01-01

    Dexamethasone (DEX) can reduce fibrous tissue growth as well as loss of residual hearing which may occur after cochlear implantation. Little is known about the effect of local inner ear DEX treatment on the spiral ganglion neurons (SGN), which are the target of the electrical stimulation with a cochlear implant (CI). Three different clinically relevant strategies of DEX-delivery into the inner ear were used. DEX was either eluted from the electrode carriers' silicone, released from a reservoir by passive diffusion, or actively applied using a pump based system. The effect of the locally applied DEX on SGN density, size and function was evaluated. DEX did not affect the SGN density compared to the relevant control groups. Simultaneously applied with chronic electrical stimulation (ES), DEX increased the neuroprotective effect of ES in the basal region and the hearing threshold tended to decrease. The EABR thresholds did not correlate with the relevant SGN density. When correlating the SGN number with fibrosis, no dependency was observed. DEX concentrations as applied in these animal models are safe for inner ear delivery in terms of their effect on SGN density. Additionally, DEX tends to improve the neuroprotective effect of chronic electrical stimulation by increasing the number of surviving neurons. This is an important finding in regard to clinical applications of DEX for local treatment of the inner ear in view of cochlear implantation and other applications.

  14. Motor imagery in REM sleep is increased by transcranial direct current stimulation of the left motor cortex (C3).

    Science.gov (United States)

    Speth, Jana; Speth, Clemens

    2016-06-01

    This study investigates if anodal transcranial direct current stimulation (tDCS) of areas above the motor cortex (C3) influences the quantity and quality of spontaneous motor imagery experienced in REM sleep. A randomized triple-blinded design was used, combining neurophysiological techniques with a tool of quantitative mentation report analysis developed from cognitive linguistics and generative grammar. The results indicate that more motor imagery, and more athletic motor imagery, is induced by anodal tDCS in comparison to cathodal and sham tDCS. This insight may have implications beyond basic consciousness research. Motor imagery in REM sleep has been hypothesized to serve the rehearsal of motor movements, which benefits later motor performance. Electrophysiological manipulations of motor imagery in REM sleep could in the long run be used for rehabilitative tDCS protocols benefitting temporarily immobile clinical patients, especially those who cannot perform specific motor imagery tasks - such as dementia patients, infants with developmental and motor disorders, and coma patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Mechanical Stimulation of C2C12 Cells Increases m-Calpain Expression and Activity, Focal Adhesion Plaque Degradation and Cell Fusion

    DEFF Research Database (Denmark)

    Grossi, Alberto; Lawson, Moira Ann; Karlsson, Anders H

    to stretch- or load-induced signaling is now beginning to be understood as a factor which affects gene sequences, protein synthesis and an increase in Ca2+ infux in myocytes. Evidence of the involvement of Ca2+ dependent activity in myoblast fusion, cell membrane and cytoskeleton component reorganization due......Abstract Mechanical Stimulation of C2C12 Cells Increases m-calpain Expression and Activity, Focal Adhesion Plaque Degradation and Cell Fusion A. Grossi, A. H. Karlsson, M. A. Lawson; Department of Dairy and Food Science, Royal Veterinary and Agricultural University, Frederiksberg C, Denmark...

  16. Exercise in patients with hypertrophic cardiomyopathy: A review of current evidence, national guideline recommendations and a proposal for a new direction to fitness.

    Science.gov (United States)

    Hindieh, Waseem; Adler, Arnon; Weissler-Snir, Adaya; Fourey, Dana; Harris, Sarah; Rakowski, Harry

    2017-04-01

    Hypertrophic cardiomyopathy is a common genetic disorder with a prevalence of 1:500 in the general population. Amongst a varied spectrum of clinical presentations, the most feared complication of this cardiac disorder is sudden cardiac death. Although only a minority of patients with hypertrophic cardiomyopathy who suffer sudden cardiac death or resuscitated cardiac arrest do so during exercise, strenuous physical activity is regarded as an important trigger for these tragic outcomes. Furthermore, during exercise, patients with hypertrophic cardiomyopathy may develop augmentation of left ventricular outflow tract obstruction, myocardial ischemia, diastolic dysfunction and/or inappropriate vasodilation in non-exercising vascular beds. This in turn may lead to exertional dyspnea, chest pain or syncope. Accordingly, patients with hypertrophic cardiomyopathy are disqualified from competitive sports and in many cases are recommended to avoid strenuous physical activity of any kind. Nevertheless, avoidance of physical activity comes with a price. The positive effects of regular exercise have been extensively reported to convey a wide range of benefits including reduced cardiovascular events, weight reduction and improved wellbeing. Therefore, finding the right exercise level that will offer some of the benefits of physical activity without increasing the risk of sudden cardiac death is of utmost importance. In this review, we discuss the current evidence for and against exercise in this patient population and review national guideline recommendations. We also propose alternative fitness strategies including a novel fitness program implemented by our hypertrophic cardiomyopathy center which may be of particular usefulness for hypertrophic cardiomyopathy patients. Copyright © 2016 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  17. Increased Frequency of Peripheral B and T Cells Expressing Granulocyte Monocyte Colony-Stimulating Factor in Rheumatoid Arthritis Patients

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    Anastasia Makris

    2018-01-01

    Full Text Available ObjectivesGranulocyte monocyte colony-stimulating factor (GM-CSF is currently considered a crucial inflammatory mediator and a novel therapeutic target in rheumatoid arthritis (RA, despite the fact that its precise cellular sources remain uncertain. We studied the expression of GM-CSF in peripheral lymphocytes from RA patients and its change with antirheumatic therapies.MethodsIntracellular GM-CSF expression was assessed by flow cytometry in stimulated peripheral B (CD19+ and T (CD3+ cells from RA patients (n = 40, disease (n = 31 including osteoarthritis n = 15, psoriatic arthritis n = 10, and systemic rheumatic diseases n = 6 and healthy (n = 16 controls. The phenotype of GM-CSF+ B cells was assessed as well as longitudinal changes in GM-CSF+ lymphocytes during methotrexate (MTX, n = 10 or anti-tumor necrosis factor (anti-TNF, n = 10 therapy.ResultsAmong untreated RA patients with active disease (Disease Activity Score 28-C-reactive protein = 5.6 ± 0.89 an expanded population of peripheral GM-CSF+ B (4.1 ± 2.2% and T (3.4 ± 1.6% cells was detected compared with both disease (1.7 ± 0.9%, p < 0.0001 and 1.7 ± 1.3%, p < 0.0001, respectively and healthy (0.3 ± 0.2%, p < 0.0001 and 0.6 ± 0.6%, p < 0.0001 controls. RA GM-CSF+ B cells displayed more commonly a plasmablast or transitional phenotype (37.12 ± 18.34% vs. 14.26 ± 9.46%, p = 0.001 and 30.49 ± 15.04% vs. 2.45 ± 1.84%, p < 0.0001, respectively and less a memory phenotype (21.46 ± 20.71% vs. 66.99 ± 16.63%, p < 0.0001 compared to GM-CSF− cells. GM-CSF expression in RA patients did not correlate to disease duration, activity or serological status. Anti-TNF treatment led to a statistically significant decrease in GM-CSF+ B and T cells while MTX had no significant effect.DiscussionThis is the first study showing an expanded population of GM-CSF+ B and T lymphocytes

  18. Immunomodulation Induced by Stem Cell Mobilization and Harvesting in Healthy Donors: Increased Systemic Osteopontin Levels after Treatment with Granulocyte Colony-Stimulating Factor.

    Science.gov (United States)

    Melve, Guro Kristin; Ersvaer, Elisabeth; Akkök, Çiğdem Akalın; Ahmed, Aymen Bushra; Kristoffersen, Einar K; Hervig, Tor; Bruserud, Øystein

    2016-07-19

    Peripheral blood stem cells from healthy donors mobilized by granulocyte colony-stimulating factor (G-CSF) and harvested by leukapheresis are commonly used for allogeneic stem cell transplantation. The frequency of severe graft versus host disease is similar for patients receiving peripheral blood and bone marrow allografts, even though the blood grafts contain more T cells, indicating mobilization-related immunoregulatory effects. The regulatory phosphoprotein osteopontin was quantified in plasma samples from healthy donors before G-CSF treatment, after four days of treatment immediately before and after leukapheresis, and 18-24 h after apheresis. Myeloma patients received chemotherapy, combined with G-CSF, for stem cell mobilization and plasma samples were prepared immediately before, immediately after, and 18-24 h after leukapheresis. G-CSF treatment of healthy stem cell donors increased plasma osteopontin levels, and a further increase was seen immediately after leukapheresis. The pre-apheresis levels were also increased in myeloma patients compared to healthy individuals. Finally, in vivo G-CSF exposure did not alter T cell expression of osteopontin ligand CD44, and in vitro osteopontin exposure induced only small increases in anti-CD3- and anti-CD28-stimulated T cell proliferation. G-CSF treatment, followed by leukapheresis, can increase systemic osteopontin levels, and this effect may contribute to the immunomodulatory effects of G-CSF treatment.

  19. Nitroxyl (HNO stimulates soluble guanylyl cyclase to suppress cardiomyocyte hypertrophy and superoxide generation.

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    Eliane Q Lin

    Full Text Available New therapeutic targets for cardiac hypertrophy, an independent risk factor for heart failure and death, are essential. HNO is a novel redox sibling of NO• attracting considerable attention for the treatment of cardiovascular disorders, eliciting cGMP-dependent vasodilatation yet cGMP-independent positive inotropy. The impact of HNO on cardiac hypertrophy (which is negatively regulated by cGMP however has not been investigated.Neonatal rat cardiomyocytes were incubated with angiotensin II (Ang II in the presence and absence of the HNO donor Angeli's salt (sodium trioxodinitrate or B-type natriuretic peptide, BNP (all 1 µmol/L. Hypertrophic responses and its triggers, as well as cGMP signaling, were determined.We now demonstrate that Angeli's salt inhibits Ang II-induced hypertrophic responses in cardiomyocytes, including increases in cardiomyocyte size, de novo protein synthesis and β-myosin heavy chain expression. Angeli's salt also suppresses Ang II induction of key triggers of the cardiomyocyte hypertrophic response, including NADPH oxidase (on both Nox2 expression and superoxide generation, as well as p38 mitogen-activated protein kinase (p38MAPK. The antihypertrophic, superoxide-suppressing and cGMP-elevating effects of Angeli's salt were mimicked by BNP. We also demonstrate that the effects of Angeli's salt are specifically mediated by HNO (with no role for NO• or nitrite, with subsequent activation of cardiomyocyte soluble guanylyl cyclase (sGC and cGMP signaling (on both cGMP-dependent protein kinase, cGK-I and phosphorylation of vasodilator-stimulated phosphoprotein, VASP.Our results demonstrate that HNO prevents cardiomyocyte hypertrophy, and that cGMP-dependent NADPH oxidase suppression contributes to these antihypertrophic actions. HNO donors may thus represent innovative pharmacotherapy for cardiac hypertrophy.

  20. Pathophysiology and meaning of washout rate in hypertrophic heart. Comparison between hypertensive cardiac hypertrophy and hypertrophic cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Nitta, Yutaka (Kanazawa Univ. (Japan). School of Medicine)

    1989-02-01

    The present study was attempted to clarify clinically the pathogenesis of hypertensive cardiac hypertrophy (HT) and hypertrophic cardiomyopathy (HCM). The exercise thallium-201 (Tl-201) myocardial scintigraphy by bicycle ergometer was performed in three groups: control, HT and HCM. The scintigrams were evaluated by circumferential profile analysis. Furthermore, the change of Tl-201 dynamics of exercise Tl-201 scintigraphy with verapamil injection was compared with the change of coronary sinus flow after verapamil injection at cardiac catheterization. The analysis of exercise Tl-201 scintigraphy without verapamil injection showed that initial uptake was not different among the three groups, but washout rate at three hours after Tl-201 injection (WR{sub 3}) was different among the three groups. Although WR{sub 3} of HT was not different from that of control, WR{sub 3} of HCM was lower than that of control. Comparison of WR{sub 3} with and without verapamil was performed. Although WR{sub 3} with verapamil injection was equal to that without verapamil injection in control and HT, WR{sub 3} with verapamil injection decreased compared to that without verapamil injection in HCM. As an index at the time that circulation changes rapidly and on a large scale, washout rate at one hour after Tl-201 injection (WR{sub 1}) was calculated. WR{sub 1} without verapamil injection was not different in the three groups and did not differ from that with verapamil injection in each group. By intravenous administration of verapamil, coronary sinus flow (CSF) increased to the same extent in the three groups. And the increment of CSF was not different in the three groups. (J.P.N.).

  1. Increases in terrestrially derived carbon stimulate organic carbon processing and CO2 emissions in boreal aquatic ecosystems

    Science.gov (United States)

    Lapierre, Jean-François; Guillemette, François; Berggren, Martin; Del Giorgio, Paul A.

    2013-12-01

    The concentrations of terrestrially derived dissolved organic carbon have been increasing throughout northern aquatic ecosystems in recent decades, but whether these shifts have an impact on aquatic carbon emissions at the continental scale depends on the potential for this terrestrial carbon to be converted into carbon dioxide. Here, via the analysis of hundreds of boreal lakes, rivers and wetlands in Canada, we show that, contrary to conventional assumptions, the proportion of biologically degradable dissolved organic carbon remains constant and the photochemical degradability increases with terrestrial influence. Thus, degradation potential increases with increasing amounts of terrestrial carbon. Our results provide empirical evidence of a strong causal link between dissolved organic carbon concentrations and aquatic fluxes of carbon dioxide, mediated by the degradation of land-derived organic carbon in aquatic ecosystems. Future shifts in the patterns of terrestrial dissolved organic carbon in inland waters thus have the potential to significantly increase aquatic carbon emissions across northern landscapes.

  2. Pregnancy in women with hypertrophic cardiomyopathy : data from the European Society of Cardiology initiated Registry of Pregnancy and Cardiac disease (ROPAC)

    NARCIS (Netherlands)

    Goland, S.; van Hagen, I. M.; Elbaz-Greener, G.; Elkayam, U.; Shotan, A.; Merz, W. M.; Enar, S. C.; Gaisin, I. R.; Pieper, P. G.; Johnson, M. R.; Hall, R.; Blatt, A.; Roos-Hesselink, J. W.

    2017-01-01

    Aims We report the maternal and foetal outcomes at birth and after 6 months in a cohort of pregnant women with hypertrophic cardiomyopathy (HCM). Although most women with HCM tolerate pregnancy well, there is an increased risk of obstetric and cardiovascular complications. Methods and results All

  3. Potential mechanisms for a role of metabolic stress in hypertrophic adaptations to resistance training.

    Science.gov (United States)

    Schoenfeld, Brad J

    2013-03-01

    It is well established that regimented resistance training can promote increases in muscle hypertrophy. The prevailing body of research indicates that mechanical stress is the primary impetus for this adaptive response and studies show that mechanical stress alone can initiate anabolic signalling. Given the dominant role of mechanical stress in muscle growth, the question arises as to whether other factors may enhance the post-exercise hypertrophic response. Several researchers have proposed that exercise-induced metabolic stress may in fact confer such an anabolic effect and some have even suggested that metabolite accumulation may be more important than high force development in optimizing muscle growth. Metabolic stress pursuant to traditional resistance training manifests as a result of exercise that relies on anaerobic glycolysis for adenosine triphosphate production. This, in turn, causes the subsequent accumulation of metabolites, particularly lactate and H(+). Acute muscle hypoxia associated with such training methods may further heighten metabolic buildup. Therefore, the purpose of this paper will be to review the emerging body of research suggesting a role for exercise-induced metabolic stress in maximizing muscle development and present insights as to the potential mechanisms by which these hypertrophic adaptations may occur. These mechanisms include increased fibre recruitment, elevated systemic hormonal production, alterations in local myokines, heightened production of reactive oxygen species and cell swelling. Recommendations are provided for potential areas of future research on the subject.

  4. Prenatal exposure to ethanol stimulates hypothalamic CCR2 chemokine receptor system: Possible relation to increased density of orexigenic peptide neurons and ethanol drinking in adolescent offspring

    Science.gov (United States)

    Chang, G.-Q.; Karatayev, O.; Leibowitz, S. F.

    2015-01-01

    Clinical and animal studies indicate that maternal consumption of ethanol during pregnancy increases alcohol drinking in the offspring. Possible underlying mechanisms may involve orexigenic peptides, which are stimulated by prenatal ethanol exposure and themselves promote drinking. Building on evidence that ethanol stimulates neuroimmune factors such as the chemokine CCL2 that in adult rats is shown to colocalize with the orexigenic peptide, melanin-concentrating hormone (MCH) in the lateral hypothalamus (LH), the present study sought to investigate the possibility that CCL2 or its receptor CCR2 in LH are stimulated by prenatal ethanol exposure, perhaps specifically within MCH neurons. Our paradigm of intraoral administration of ethanol to pregnant rats, at low-to-moderate doses (1 or 3 g/kg/day) during peak hypothalamic neurogenesis, caused in adolescent male offspring two-fold increase in drinking of and preference for ethanol and reinstatement of ethanol drinking in a two-bottle choice paradigm under an intermittent access schedule. This effect of prenatal ethanol exposure was associated with an increased expression of MCH and density of MCH+ neurons in LH of preadolescent offspring. Whereas CCL2+ cells at this age were low in density and unaffected by ethanol, CCR2+ cells were dense in LH and increased by prenatal ethanol, with a large percentage (83–87%) identified as neurons and found to colocalize MCH. Prenatal ethanol also stimulated the genesis of CCR2+ and MCH+ neurons in the embryo, which co-labeled the proliferation marker, BrdU. Ethanol also increased the genesis and density of neurons that co-expressed CCR2 and MCH in LH, with triple-labeled CCR2+/MCH+/BrdU+ neurons that were absent in control rats accounting for 35% of newly generated neurons in ethanol-exposed rats. With both the chemokine and MCH systems believed to promote ethanol consumption, this greater density of CCR2+/MCH+ neurons in the LH of preadolescent rats suggests that these systems

  5. CXCL4 Exposure Potentiates TLR-Driven Polarization of Human Monocyte-Derived Dendritic Cells and Increases Stimulation of T Cells.

    Science.gov (United States)

    Silva-Cardoso, Sandra C; Affandi, Alsya J; Spel, Lotte; Cossu, Marta; van Roon, Joel A G; Boes, Marianne; Radstake, Timothy R D J

    2017-07-01

    Chemokines have been shown to play immune-modulatory functions unrelated to steering cell migration. CXCL4 is a chemokine abundantly produced by activated platelets and immune cells. Increased levels of circulating CXCL4 are associated with immune-mediated conditions, including systemic sclerosis. Considering the central role of dendritic cells (DCs) in immune activation, in this article we addressed the effect of CXCL4 on the phenotype and function of monocyte-derived DCs (moDCs). To this end, we compared innate and adaptive immune responses of moDCs with those that were differentiated in the presence of CXCL4. Already prior to TLR- or Ag-specific stimulation, CXCL4-moDCs displayed a more matured phenotype. We found that CXCL4 exposure can sensitize moDCs for TLR-ligand responsiveness, as illustrated by a dramatic upregulation of CD83, CD86, and MHC class I in response to TLR3 and TLR7/8-agonists. Also, we observed a markedly increased secretion of IL-12 and TNF-α by CXCL4-moDCs exclusively upon stimulation with polyinosinic-polycytidylic acid, R848, and CL075 ligands. Next, we analyzed the effect of CXCL4 in modulating DC-mediated T cell activation. CXCL4-moDCs strongly potentiated proliferation of autologous CD4(+) T cells and CD8(+) T cells and production of IFN-γ and IL-4, in an Ag-independent manner. Although the internalization of Ag was comparable to that of moDCs, Ag processing by CXCL4-moDCs was impaired. Yet, these cells were more potent at stimulating Ag-specific CD8(+) T cell responses. Together our data support that increased levels of circulating CXCL4 may contribute to immune dysregulation through the modulation of DC differentiation. Copyright © 2017 by The American Association of Immunologists, Inc.

  6. Ginkgolide B reduces LOX-1 expression by inhibiting Akt phosphorylation and increasing Sirt1 expression in oxidized LDL-stimulated human umbilical vein endothelial cells.

    Directory of Open Access Journals (Sweden)

    Lina Ma

    Full Text Available Oxidized low-density lipoprotein (ox-LDL is an important risk factor in the development of atherosclerosis. LOX-1, a lectin-like receptor for ox-LDL, is present primarily on endothelial cells and upregulated by ox-LDL, tumor necrosis factor a, shear stress, and cytokines in atherosclerosis. Recent studies demonstrated that ginkgolide B, a platelet-activating factor receptor antagonist, has antiinflammatory and antioxidant effects on endothelial and nerve cells. The present study investigated the effects of ginkgolide B on LOX-1 expression and the possible mechanism of action. Our results showed that ginkgolide B inhibited LOX-1 and intercellular cell adhesion molecule-1 (ICAM-1 expression in ox-LDL-stimulated endothelial cells through a mechanism associated with the attenuation of Akt activation. Similar data were obtained by silencing Akt and LY294002. We also evaluated Sirt1 and nuclear factor erythroid 2-related factor 2 (Nrf2 expression. These molecules play a protective role in endothelial cell injury. The results showed that ginkgolide B increased Sirt1 expression in ox-LDL-treated cells. The inhibitory effects of ginkgolide B on LOX-1 and ICAM-1 expression were reduced in Sirt1 siRNA-transfected cells. Nrf2 expression was increased in ox-LDL-treated cells, and ginkgolide B downregulated Nrf2 expression. These results suggest that ginkgolide B reduces Nrf2 expression by inhibiting LOX-1 expression, consequently reducing oxidative stress injury in ox-LDL-stimulated cells. Altogether, these results indicate that the protective effect of ginkgolide B on endothelial cells may be attributable to a decrease in LOX-1 expression and an increase in Sirt1 expression in ox-LDL-stimulated endothelial cells, the mechanism of which is linked to the inhibition of Akt activation. Ginkgolide B may be a multiple-target drug that exerts protective effects in ox-LDL-treated human umbilical vein endothelial cells.

  7. IL-33 stimulates the release of procoagulant microvesicles from human monocytes and differentially increases tissue factor in human monocyte subsets.

    Science.gov (United States)

    Stojkovic, Stefan; Thulin, Åsa; Hell, Lena; Thaler, Barbara; Rauscher, Sabine; Baumgartner, Johanna; Gröger, Marion; Ay, Cihan; Demyanets, Svitlana; Neumayer, Christoph; Huk, Ihor; Spittler, Andreas; Huber, Kurt; Wojta, Johann; Siegbahn, Agneta; Åberg, Mikael

    2017-06-28

    Monocytes and monocyte-derived microvesicles (MVs) are the main source of circulating tissue factor (TF). Increased monocyte TF expression and increased circulating levels of procoagulant MVs contribute to the formation of a prothrombotic state in patients with cardiovascular disease. Interleukin (IL)-33 is a pro-inflammatory cytokine involved in atherosclerosis and other inflammatory diseases, but its role in regulating thrombosis is still unclear. The aim of the present study was to investigate the effects of IL-33 on the procoagulant properties of human monocytes and monocyte-derived MVs. IL-33 induced a time- and concentration-dependent increase of monocyte TF mRNA and protein levels via binding to the ST2-receptor and activation of the NF-κB-pathway. The IL-33 treated monocytes also released CD14+TF+ MVs and IL-33 was found to increase the TF activity of both the isolated monocytes and monocyte-derived MVs. The monocytes were classified into subsets according to their CD14 and CD16 expression. Intermediate monocytes (IM) showed the highest ST2 receptor expression, followed by non-classical monocytes (NCM), and classical monocytes (CM). IL-33 induced a significant increase of TF only in the IM (p<0.01), with a tendency in NCM (p=0.06), but no increase was observed in CM. Finally, plasma levels of IL-33 were positively correlated with CD14+TF+ MVs in patients undergoing carotid endarterectomy (r=0.480; p=0.032; n=20). We hereby provide novel evidence that the proinflammatory cytokine IL-33 induces differential TF expression and activity in monocyte subsets, as well as the release of procoagulant MVs. In this manner, IL-33 may contribute to the formation of a prothrombotic state characteristic for cardiovascular disease.

  8. Thyroid stimulating immunoglobulins in Graves' disease with goitre growth, low thyroxine and increasing triiodothyronine during PTU treatment

    DEFF Research Database (Denmark)

    Hegedüs, Laszlo; Hansen, J M; Bech, K

    1984-01-01

    In 50 consecutive patients with Graves' disease treated with PTU, 7 (group 1) developed increasing goitre in spite of unmeasurable TSH. Thyroid variables were compared with those from 10 controls with an ordinary response to PTU (group 2). Serum T4 decreased in group 1 from 246 +/- 47 nmol/l (mean...

  9. Atrial myxoma in a patient with hypertrophic cardiomyopathy.

    Science.gov (United States)

    Abdou, Mahmoud; Hayek, Salim; Williams, Byron R

    2013-01-01

    Atrial myxoma is the most common primary cardiac tumor. Patients with atrial myxoma typically present with obstructive, embolic, or systemic symptoms; asymptomatic presentation is very rare. To our knowledge, isolated association of atrial myxoma with hypertrophic cardiomyopathy has been reported only once in the English-language medical literature. We report the case of an asymptomatic 71-year-old woman with known hypertrophic cardiomyopathy in whom a left atrial mass was incidentally identified on cardiac magnetic resonance images. After surgical excision of the mass and partial excision of the left atrial septum, histopathologic analysis confirmed the diagnosis of atrial myxoma. The patient was placed on preventive implantable cardioverter-defibrillator therapy and remained asymptomatic. The management of asymptomatic cardiac myxoma is a topic of debate, because no reports definitively favor either conservative or surgical measures.

  10. Prosthodontist contribution in treating post-burn hypertrophic facial scars

    Directory of Open Access Journals (Sweden)

    Padmanabhan T

    2010-01-01

    Full Text Available The formation of hypertrophic scars is common following healing of the burn wound, particularly in children. The face is one of the areas of the body most frequently affected by burns. Scar formation as a result of burn wounds leads to contraction of the formed granulation tissue, which causes both aesthetic and functional impairment for the patient. Scarring has major psychological and physical repercussions. Scarring on the face and visible regions of the body can be very distressing for the patient. Prevention of scars involves early and continuous use of a compressive orthesis. However, their efficacy is often limited to the facial region because of the contours of this area of body. This paper describes a clinical case of post-burn hypertrophic scars treated with silicone gel sheeting applied with pressure under custom made auto-polymerizing resin stent.

  11. Higher copeptin levels are associated with worse outcome in patients with hypertrophic cardiomyopathy.

    Science.gov (United States)

    Sahin, Irfan; Gungor, Baris; Ozkaynak, Berk; Uzun, Fatih; Küçük, Suat Hayri; Avci, Ilhan Iker; Ozal, Ender; Ayça, Burak; Cetın, Sukru; Okuyan, Ertugrul; Dinckal, Mustafa Hakan

    2017-01-01

    Correlation of increased copeptin levels with various cardiovascular diseases has been described. The clinical use of copeptin levels in patients with hypertrophic cardiomyopathy (HCM) has not been investigated before. In this study, we aimed to investigate the prognostic value of copeptin levels in patients with hypertrophic cardiomyopathy (HCM). HCM was defined as presence of left ventricular wall thickness ≥15 mm in a subject without any concomitant disease that may cause left ventricular hypertrophy. Levels of copeptin and plasma N-terminal probrain natriuretic peptide (NT-proBNP) were evaluated prospectively in 24 obstructive HCM patients, 36 nonobstructive HCM patients, and 36 age- and sex-matched control subjects. Blood samples were collected in the morning between 7 and 9 am after overnight fasting. Patients were followed for 24 months. Hospitalization with diagnosis of heart failure/arrhythmia, implantable cardioverter-defibrillator implantation, and cardiac mortality were accepted as adverse cardiac events. Copeptin and NT-proBNP levels were higher in the HCM group compared with controls (14.1 vs 8.4 pmol/L, P Copeptin and NT-proBNP levels were higher in the obstructive HCM subgroup compared with the nonobstructive HCM subgroup (18.3 vs 13.1 pmol/L, P copeptin and NT-proBNP levels remained as independent predictors of heart failure (P Copeptin and NT-proBNP levels were significantly higher in patients with obstructive HCM, and higher levels were associated with worse outcome. © 2016 Wiley Periodicals, Inc.

  12. Virtual Cardiac Surgery Using CFD: Application to Septal Myectomy in Obstructive Hypertrophic Cardiomyopathy

    Science.gov (United States)

    Vedula, Vijay; Mittal, Rajat; Abraham, Theodore

    2011-11-01

    Obstructive hypertrophic cardiomyopathy (HOCM) is characterized by ventricular wall thickening, diastolic dysfunction, and dynamic outflow tract obstruction, all of which strongly influence the vortex dynamics and pressure distribution in the left ventricle (LV). Severe cases of HCM are usually managed through septal myectomy where the surgeon resects the hypertrophic mass. Surgeons currently try to remove as much tissue as possible in order to optimize the post surgical result. However, excessive debulking increases the chance of ventricular septal defects, bundle branch block or complete heart block, and aneurysmal septal thinning. On the other hand, insufficient tissue removal also leads to unsatisfactory outcomes in terms of reduction of outflow tract pressure gradient. Knowing how much muscle to remove and where to remove it from could reduce the likelihood of complications and suboptimal outcomes. In the present study, we employ an immersed boundary solver to model the effect of septal myectomy for ventricles with HOCM and demonstrate the potential of such an approach for surgical planning. Computational resources were provided by the National Institute of Computational Science under Tergrid grant number TG-CTS100002.

  13. Ultrasound-guided paravertebral block for pyloromyotomy in 3 neonates with congenital hypertrophic pyloric stenosis

    Directory of Open Access Journals (Sweden)

    Javier Mata-Gómez

    2015-08-01

    Full Text Available BACKGROUND AND OBJECTIVES: Hypertrophic pyloric stenosis is a relatively common affection of gastrointestinal tract in childhood that results in symptoms, such as projectile vomiting and metabolic disorders that imply a high risk of aspiration during anesthetic induction. In this way, the carrying out of a technique with general anesthesia and intravenous rapid sequence induction, preoxygenation and cricoid pressure are recommended. After the correction of systemic metabolic alkalosis and pH normalization, cerebrospinal fluid can keep a state of metabolic alkalosis. This circumstance, in addition to the residual effect of neuromuscular blocking agents, inhalant anesthetics and opioids could increase the risk of postoperative apnea after a general anesthesia.CASE REPORT: We present the successful management in 3 neonates in those a pyloromyotomy was carried out because they had presented congenital hypertrophic pyloric stenosis. This procedure was done under general anesthesia with orotracheal intubation and rapid sequence induction. Then, ultrasound-guided paravertebral block was performed as analgesic method without the need for administrating opioids within intraoperative period and keeping an appropriate analgesic level.CONCLUSIONS: Local anesthesia has demonstrated to be safe and effective in pediatric practice. We consider the ultrasound-guided paravertebral block with one dose as a possible alternative for other local techniques described, avoiding the use of opioids and neuromuscular blocking agents during general anesthesia, and reducing the risk of central apnea within postoperative period.

  14. Hypertrophic Cardiomyopathy from A to Z: Genetics, Pathophysiology, Imaging, and Management.

    Science.gov (United States)

    Baxi, Ameya Jagdish; Restrepo, Carlos S; Vargas, Daniel; Marmol-Velez, Alejandro; Ocazionez, Daniel; Murillo, Horacio

    2016-01-01

    Hypertrophic cardiomyopathy (HCM) is a heterogeneous group of diseases related to sarcomere gene mutations exhibiting heterogeneous phenotypes with an autosomal dominant mendelian pattern of inheritance. The disorder is characterized by diverse phenotypic expressions and variable natural progression, which may range from dyspnea and/or syncope to sudden cardiac death. It is found across all racial groups and is associated with left ventricular hypertrophy in the absence of another systemic or cardiac disease. The management of HCM is based on a thorough understanding of the underlying morphology, pathophysiology, and clinical course. Imaging findings of HCM mirror the variable expressivity and penetrance heterogeneity, with the added advantage of diagnosis even in cases where a specific mutation may not yet be found. The diagnostic information obtained from imaging varies depending on the specific stage of HCM-phenotype manifestation, including the prehypertrophic, hypertrophic, and later stages of adverse remodeling into the burned-out phase of overt heart failure. However, subtle or obvious, these imaging findings become critical components in diagnosis, management, and follow-up of HCM patients. Although diagnosis of HCM traditionally relies on clinical assessment and transthoracic echocardiography, recent studies have demonstrated increased utility of multidetector computed tomography (CT) and particularly cardiac magnetic resonance (MR) imaging in diagnosis, phenotype differentiation, therapeutic planning, and prognostication. In this article, we provide an overview of the genetics, pathophysiology, and clinical manifestations of HCM, with the spectrum of imaging findings at MR imaging and CT and their contribution in diagnosis, risk stratification, and therapy. (©)RSNA, 2016.

  15. Phytoplankton biodiversity changes in a shallow tropical reservoir during the hypertrophication process

    Directory of Open Access Journals (Sweden)

    LO. Crossetti

    Full Text Available Study aimed at evaluating phytoplankton biodiversity changes in a shallow tropical reservoir during its hypertrophication process. Samplings were carried out monthly during 8 consecutive years (1997-2004 in 5 depths. Conspicuous limnological changes in the reservoir derived from the presence and/or removal of the water hyacinth, characterized 3 different phases. Over the time series, reservoir changed from a typical polymictic eutrophic system to hypertrophic one, leading to a reduction of approximately 70 species (average 37%. Chlorophyceae accounted for the highest species richness (46% among all algal classes and strictly followed total species richness variation. Internal feedback mechanisms intensification over phase III clearly promoted the sharp decrease in biodiversity. Highest decreases, mainly during springs, occurred simultaneously to the highest Cyanobacteria blooms. Increased turbidity due to heavy phytoplankton blooms suppressed all other algal groups, so that at the end of the present study even Cyanobacteria species richness decreased. Total dissolved phosphorous was included in most of the best selected models used to analyze the temporal patterns in species richness loss. Present data show that biodiversity loss following trophic change was not a single dimension of a single factor but, rather, a template of factors (e.g. light, stability co-varying in consequence of the larger levels of biomass supported in the reservoir.

  16. Clinicopathological profiles of progressive heart failure in hypertrophic cardiomyopathy

    OpenAIRE

    Melacini, Paola; Basso, Cristina; Angelini, Annalisa; Calore, Chiara; Bobbo, Fabiana; Tokajuk, Barbara; Bellini, Nicoletta; Smaniotto, Gessica; Zucchetto, Mauro; Iliceto, Sabino; Thiene, Gaetano; Maron, Barry J.

    2010-01-01

    Aims Hypertrophic cardiomyopathy (HCM) is an important cause of heart failure-related disability over a wide range of ages. Profiles of severe progressive heart failure symptoms and death, or heart transplantation deserve more complete definition within large patient cohorts. Methods and results Clinical and morphological features of heart failure were assessed in 293 consecutive HCM patients over a median follow-up of 6 (inter-quartile range 2?11) years. Gross and histopathological features ...

  17. Hypertrophic neuropathy in Noonan syndrome with multiple lentigines.

    Science.gov (United States)

    Maridet, Claire; Sole, Guilhem; Morice-Picard, Fanny; Taieb, Alain

    2016-06-01

    RASopathies comprise several genetic syndromes with mainly cardio-facial-cutaneous manifestations. We report a patient with Noonan syndrome with multiple lentigines (NSML) due to a PTPN11 (p.Thr468Met) mutation associated with hypertrophic neuropathy of lumbar plexus in an adult woman, initially referred for neuropathic pain. Differential diagnosis of neurofibromatosis type 1 (NF1) and other RASopathies is difficult without molecular testing. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  18. Cardiac troponin T and familial hypertrophic cardiomyopathy: an energetic affair

    Science.gov (United States)

    Schwartz, Ketty; Mercadier, Jean-Jacques

    2003-01-01

    It has long been noted that while patients with familial hypertrophic cardiomyopathy due to cardiac troponin T (cTnT) mutations often suffer sudden cardiac death, they do not develop significant ventricular hypertrophy, suggesting that a distinct cellular mechanism apart from alterations in myocardial contractility is responsible. A new study has revealed that a single missense mutation in cTnT causes a striking disruption to energy metabolism, leading to cardiomyopathy. PMID:12952912

  19. Pyocyanin stimulates quorum sensing-mediated tolerance to oxidative stress and increases persister cell populations in Acinetobacter baumannii.

    Science.gov (United States)

    Bhargava, Nidhi; Sharma, Prince; Capalash, Neena

    2014-08-01

    Acinetobacter baumannii and Pseudomonas aeruginosa are nosocomial pathogens with overlapping sites of infection. This work reports that the two can coexist stably in mixed-culture biofilms. In a study intended to improve our understanding of the mechanism of their coexistence, it was found that pyocyanin, produced by P. aeruginosa that generally eliminates competition from other pathogens, led to the generation of reactive oxygen species (ROS) in A. baumannii cells, which in response showed a significant (P ≤ 0.05) increase in production of enzymes, specifically, catalase and superoxide dismutase (SOD). This work shows for the first time that the expression of catalase and SOD is under the control of a quorum-sensing system in A. baumannii. In support of this observation, a quorum-sensing mutant of A. baumannii (abaI::Km) was found to be sensitive to pyocyanin compared to its wild type and showed significantly (P ≤ 0.001) lower levels of the antioxidant enzymes, which increased on addition of 5 μM N-(3-hydroxydodecanoyl)-l-homoserine lactone. Likewise, in wild-type A. baumannii, there was a significant (P pyocyanin. These findings show that pyocyanin induces a protective mechanism in A. baumannii against oxidative stress and also increases its persistence against antibiotics which could be of clinical significance in the case of coinfections with A. baumannii and P. aeruginosa. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  20. Peroxynitrite formed during a transient episode of brain ischaemia increases endothelium-derived hyperpolarization-type dilations in thromboxane/prostaglandin receptor-stimulated rat cerebral arteries.

    Science.gov (United States)

    Onetti, Y; Dantas, A P; Pérez, B; McNeish, A J; Vila, E; Jiménez-Altayó, F

    2017-05-01

    Increased thromboxane A 2 and peroxynitrite are hallmarks of cerebral ischaemia/reperfusion (I/R). Stimulation of thromboxane/prostaglandin receptors (TP) attenuates endothelium-derived hyperpolarization (EDH). We investigated whether EDH-type middle cerebral artery (MCA) relaxations following TP stimulation are altered after I/R and the influence of peroxynitrite. Vascular function was determined by wire myography after TP stimulation with the thromboxane A 2 mimetic 9,11-dideoxy-9α, 11α -methano-epoxy prostaglandin F2α (U46619) in MCA of Sprague Dawley rats subjected to MCA occlusion (90 min)/reperfusion (24 h) or sham operation, and in non-operated (control) rats. Some rats were treated with saline or the peroxynitrite decomposition catalyst 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrinato iron (III) (20 mg kg -1 ). Protein expression was evaluated in MCA and in human microvascular endothelial cells submitted to hypoxia (overnight)/reoxygenation (24 h) (H/R) using immunofluorescence and immunoblotting. In U46619-pre-constricted MCA, EDH-type relaxation by the proteinase-activated receptor 2 agonist serine-leucine-isoleucine-glycine-arginine-leucine-NH 2 (SLIGRL) was greater in I/R than sham rats due to an increased contribution of small-conductance calcium-activated potassium channels (SK C a ), which was confirmed by the enlarged relaxation to the SK C a activator N-cyclohexyl-N-2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-4-pyrimidinamine. I/R and H/R induced endothelial protein tyrosine nitration and filamentous-actin disruption. In control MCA, either cytochalasin D or peroxynitrite disrupted endothelial filamentous-actin and augmented EDH-type relaxation. Furthermore, peroxynitrite decomposition during I/R prevented the increase in EDH-type responses. Following TP stimulation in MCA, EDH-type relaxation to SLIGRL is greater after I/R due to endothelial filamentous-actin disruption by peroxynitrite, which prevents TP-induced block of SK C a input to EDH

  1. Exercise training favors increased insulin-stimulated glucose uptake in skeletal muscle in contrast to adipose tissue: a randomized study using FDG PET imaging.

    Science.gov (United States)

    Reichkendler, M H; Auerbach, P; Rosenkilde, M; Christensen, A N; Holm, S; Petersen, M B; Lagerberg, A; Larsson, H B W; Rostrup, E; Mosbech, T H; Sjödin, A; Kjaer, A; Ploug, T; Hoejgaard, L; Stallknecht, B

    2013-08-15

    Physical exercise increases peripheral insulin sensitivity, but regional differences are poorly elucidated in humans. We investigated the effect of aerobic exercise training on insulin-stimulated glucose uptake in five individual femoral muscle groups and four different adipose tissue regions, using dynamic (femoral region) and static (abdominal region) 2-deoxy-2-[¹⁸F]fluoro-d-glucose (FDG) PET/CT methodology during steady-state insulin infusion (40 mU·m⁻²·min⁻¹). Body composition was measured by dual X-ray absorptiometry and MRI. Sixty-one healthy, sedentary [V(O2max) 36(5) ml·kg⁻¹·min⁻¹; mean(SD)], moderately overweight [BMI 28.1(1.8) kg/m²], young [age: 30(6) yr] men were randomized to sedentary living (CON; n = 17 completers) or moderate (MOD; 300 kcal/day, n = 18) or high (HIGH; 600 kcal/day, n = 18) dose physical exercise for 11 wk. At baseline, insulin-stimulated glucose uptake was highest in femoral skeletal muscle followed by intraperitoneal visceral adipose tissue (VAT), retroperitoneal VAT, abdominal (anterior + posterior) subcutaneous adipose tissue (SAT), and femoral SAT (P exercise groups in femoral skeletal muscle (MOD 24[9, 39] μmol·kg⁻¹·min⁻¹, P = 0.004; HIGH 22[9, 35] μmol·kg⁻¹·min⁻¹, P = 0.003) (mean[95% CI]) and in five individual femoral muscle groups but not in femoral SAT. Standardized uptake value of FDG decreased ~24% in anterior abdominal SAT and ~20% in posterior abdominal SAT compared with CON but not in either intra- or retroperitoneal VAT. Total adipose tissue mass decreased in both exercise groups, and the decrease was distributed equally among subcutaneous and intra-abdominal depots. In conclusion, aerobic exercise training increases insulin-stimulated glucose uptake in skeletal muscle but not in adipose tissue, which demonstrates some interregional differences.

  2. Management of Keloid and Hypertrophic Scar/span>s

    Science.gov (United States)

    Edriss, A.S.; Mesták, J.

    2005-01-01

    Summary Scar management for the prevention of excessive scar formation has always been important but never so important as it is today. Optimal management continues to be an enigma for surgeons, and the best modality of treatment has been debated for many years. However, most studies have unfortunately been either retrospective or case report descriptions. Advances in scar management have been hampered by confusing or ambiguous terminology. There is no consensus on what amount of post-traumatic skin scar formation is "normal" and what should be considered "hypertrophic". In the World Health Organization's ICD-9, there is no diagnostic code for hypertrophic scar - only keloid is listed. Yet the medical and scientific literature distinguishes them as different conditions. This confusion results in inappropriate management of scar formation, and occasionally contributes to decision making related to elective or cosmetic surgery. Our experience suggests that there is no single treatment for scars that is adequate and that clinical judgement is very important when considering treatment and balancing the potential benefits of the various treatments available. The goal of treating scars is to restore functionality, provide relief of symptoms, enhance cosmetics, and prevent recurrence. This article is based on our scientific and clinical experiences and focuses on over-the-counter options to manage keloid and hypertrophic scar/span>s. PMID:21991008

  3. Two cases of apical ballooning syndrome masking apical hypertrophic cardiomyopathy.

    Science.gov (United States)

    Roy, Ranjini Raina; Hakim, Fayaz A; Hurst, R Todd; Simper, David; Appleton, Christopher P

    2014-04-01

    Apical akinesis and dilation in the absence of obstructive coronary artery disease is a typical feature of stress-induced (takotsubo) cardiomyopathy, whereas apical hypertrophy is seen in apical-variant hypertrophic cardiomyopathy. We report the cases of 2 patients who presented with takotsubo cardiomyopathy and were subsequently found to have apical-variant hypertrophic cardiomyopathy, after the apical ballooning from the takotsubo cardiomyopathy had resolved. The first patient, a 43-year-old woman with a history of alcohol abuse, presented with shortness of breath, electrocardiographic and echocardiographic features consistent with takotsubo cardiomyopathy, and no significant coronary artery disease. An echocardiogram 2 weeks later revealed a normal left ventricular ejection fraction and newly apparent apical hypertrophy. The 2nd patient, a 70-year-old woman with pancreatitis, presented with chest pain, apical akinesis, and a left ventricular ejection fraction of 0.39, consistent with takotsubo cardiomyopathy. One month later, her left ventricular ejection fraction was normal; however, hypertrophy of the left ventricular apex was newly noted. To our knowledge, these are the first reported cases in which apical-variant hypertrophic cardiomyopathy was masked by apical ballooning from stress-induced cardiomyopathy.

  4. Left Atrial Mechanical Function and Global Strain in Hypertrophic Cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Kyung-Jin Kim

    Full Text Available Atrial fibrillation is the most common arrhythmia and is associated with adverse outcomes in hypertrophic cardiomyopathy (HCM. Although left atrial (LA remodeling and dysfunction are known to associate with the development of atrial fibrillation in HCM, the changes of the LA in HCM patients remain unclear. This study aimed to evaluate the changes in LA size and mechanical function in HCM patients compared to control subjects and to determine the characteristics of HCM associated with LA remodeling and dysfunction.Seventy-nine HCM patients (mean age, 54 ± 11 years; 76% were men were compared to 79 age- and sex-matched controls (mean age, 54 ± 11 years; 76% were men and 20 young healthy controls (mean age, 33 ± 5 years; 45% were men. The LA diameter, volume, and mechanical function, including global strain (ε, were evaluated by 2D-speckle tracking echocardiography. The phenotype of HCM, maximal left ventricular (LV wall thickness, LV mass, and presence and extent of late gadolinium enhancement (LGE were evaluated with cardiac magnetic resonance imaging.HCM patients showed increased LA volume index, impaired reservoir function, and decreased LA ε compared to the control subjects. When we divided the HCM group according to a maximal LA volume index (LAVImax of 38.7 ml/m2 or LA ε of 21%, no significant differences in the HCM phenotype and maximal LV wall thickness were observed for patients with LAVImax >38.7 ml/m2 or LA ε ≤21%. Conversely, the LV mass index was significantly higher both in patients with maximal LA volume index >38.7 ml/m2 and with LA ε ≤21% and was independently associated with LAVImax and LA ε. Although the LGE extent was increased in patients with LA ε ≤21%, it was not independently associated with either LAVImax or LA ε.HCM patients showed progressed LA remodeling and dysfunction; the determinant of LA remodeling and dysfunction was LV mass index rather than LV myocardial fibrosis by LGE-magnetic resonance

  5. Continuous light after 2 months of long days stimulates ram testis volume and increases fertility in spring.

    Science.gov (United States)

    Chesneau, D; Guillaume, D; Chemineau, P; Malpaux, B

    2017-07-01

    Seasonal reproduction is one of the major biotechnical and economic constraints of sheep production in temperate latitudes. Treatments using extra light followed by melatonin implants have been used satisfactorily in open barns, farms and artificial insemination centres to produce out-of-season sexual activity in rams. The aim of the present study is to explore the possibility of replacing melatonin implants with continuous light (LL), which was recently shown to increase LH secretion similar to melatonin and/or pinealectomy. Four experiments during 4 consecutive years were conducted in 'Ile-de-France' rams. In each study, one group was systematically exposed to permanent light after a first photoperiodic treatment of 60 long days (LD-LL) during the winter and compared with various other control groups subjected either to a natural photoperiod or the classical LD-melatonin treatment. As expected, blood nocturnal melatonin secretion was suppressed by LL. In all four experiments, LL treatment produced a highly significant and robust increase in ram testicular volume in the spring compared with the testicular volume of control rams or of that of treated rams at the end of the LD. For the two experiments in which fertility was tested, fertility after hand-mating was significantly higher in LD-LL rams than in control rams (76% v. 64%). Therefore, permanent light after an LD treatment may be an interesting alternative to LD-melatonin treatment to induce out-of-season sexual activity in rams.

  6. SWIMMING EXERCISE STIMULATES NEURO-GENESIS IN THE SUBVENTRICULAR ZONE VIA INCREASE IN SYNAPSIN I AND NERVE GROWTH FACTOR LEVELS

    Directory of Open Access Journals (Sweden)

    Chae C-H

    2015-01-01

    Full Text Available In this study, we investigated the effects of 8-weeks of swimming exercise on neurogenesis in the subventricular zone (SVZ and on the levels of nerve growth factor (NGF and synapsin I protein in the olfactory bulb (OB of adult rats at a series of relevant time points (2 days, 1 week, 2 weeks, 4 weeks, 3 months, and 6 months. Ninety-six male Sprague Dawley rats were divided into 2 groups: (1 a control group (COG; n = 48, n = 8 for each time point and (2 a swimming exercise group (SEG; total n = 48; n = 8 for each time point. SEG performed swimming exercise for 5 days per week over a period of 8 weeks. We found that the number of 5-bromo-2’-deoxyuridine-5’-monophosphate (BrdU- and doublecortin (DCX-positive cells was significantly higher in SEG than in COG at all time points (Day 2, Week 1, Week 2, Week 4, Month 3, and Month 6; p < 0.001. Furthermore, NGF and synapsin I protein levels were significantly higher in SEG on Day 2, and Weeks 1, 2, and 4 than in COG (p < 0.05 for each time point. Our findings suggest that regular swimming exercise in adult rats increases neurogenesis, neuronal survival, and neuronal maintenance in the SVZ; furthermore, swimming exercise increases the levels of NGF and synapsin I in the OB.

  7. Intermittent theta burst over M1 may increase peak power of a Wingate anaerobic test and prevent the reduction of voluntary activation measured with transcranial magnetic stimulation

    Directory of Open Access Journals (Sweden)

    Louis-Solal Giboin

    2016-07-01

    Full Text Available Despite the potential of repetitive transcranial magnetic stimulation (rTMS to improve performances in patients suffering from motor neuronal afflictions, its effect on motor performance enhancement in healthy subjects during a specific sport task is still unknown. We hypothesised that after an intermittent theta burst (iTBS treatment, performance during the Wingate Anaerobic Test (WAnT, will increase and supraspinal fatigue following the exercise will be lower in comparison to a control treatment.Ten subjects participated in two randomised experiments consisting of a WAnT 5 minutes after either an iTBS or a control treatment. We determined voluntary activation (VA of the right knee extensors with TMS (VATMS and with peripheral nerve stimulation (VAPNS of the femoral nerve, before and after the WAnT. T-tests were applied to the WAnT results and a 2 way within subject ANOVA was applied to VA results. The iTBS treatment increased the peak power and the maximum pedalling cadence and suppressed the reduction of VATMS following the WAnT compared to the control treatment. No behavioural changes related to fatigue (mean power and fatigue index were observed.These results indicate for the first time that iTBS could be used as a potential intervention to improve anaerobic performance in a sport specific task.

  8. Caffeine Induces a Stimulant Effect and Increases Dopamine Release in the Nucleus Accumbens Shell Through the Pulmonary Inhalation Route of Administration in Rats.

    Science.gov (United States)

    Galvalisi, Martín; Prieto, José Pedro; Martínez, Marcela; Abin-Carriquiry, Juan Andrés; Scorza, Cecilia

    2017-01-01

    Oral, intraperitoneal, or intravenous have been the common routes of administration used to study the behavioral and neurochemical pharmacology of caffeine, one of the most widely used psychoactive substances worldwide. We have reported that caffeine is an active adulterant frequently found in coca-paste (CP)-seized samples, a highly addictive form of smokable cocaine. The role of caffeine in the psychostimulant and neurochemical effects induced by CP remains under study. No preclinical animal studies have been performed so far to characterize the effects of caffeine when it is administered through the pulmonary inhalation route. Caffeine (10, 25, and 50 mg) was volatilized and rats were exposed to one inhalation session of its vapor. The stimulant effect was automatically recorded and plasmatic levels of caffeine were measured. Caffeine capability (50 mg) to increase extracellular dopamine (DA) levels in nucleus accumbens shell was also studied by in vivo microdialysis in non-anesthetized animals. A dose-dependent stimulant effect induced by volatilized caffeine was observed and this effect was directly related with caffeine plasmatic levels. A significant increase in the extracellular DA was achieved after 50 mg of volatilized caffeine exposure. This is the first report showing pharmacological acute effects of caffeine through the pulmonary inhalation route of administration and suggests that this could be a condition under which caffeine can elevate its weak reinforcing effect and even enhance the psychostimulant effect and abuse liability of smokable adulterated psychostimulant drugs.

  9. Repetitive transcranial magnetic stimulation effectively facilitates spatial cognition and synaptic plasticity associated with increasing the levels of BDNF and synaptic proteins in Wistar rats.

    Science.gov (United States)

    Shang, Yingchun; Wang, Xin; Shang, Xueliang; Zhang, Hui; Liu, Zhipeng; Yin, Tao; Zhang, Tao

    2016-10-01

    Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique, by which cognitive deficits can be alleviated. Furthermore, rTMS may facilitate learning and memory. However, its underlying mechanism is still little known. The aim of this study was to investigate if the facilitation of spatial cognition and synaptic plasticity, induced by rTMS, is regulated by enhancing pre- and postsynaptic proteins in normal rats. Morris water maze (MWM) test was performed to examine the spatial cognition. The synaptic plasticity, including long-term potentiation (LTP) and depotentiation (DEP), presynaptic plasticity paired-pulse facilitation (PPF), from the hippocampal Schaffer collaterals to CA1 region was subsequently measured using in vivo electrophysiological techniques. The expressions of brain-derived neurotrophic factor (BDNF), presynaptic protein synaptophysin (SYP) and postsynaptic protein NR2B were measured by Western blot. Our data show that the spatial learning/memory and reversal learning/memory in rTMS rats were remarkably enhanced compared to that in the Sham group. Furthermore, LTP and DEP as well as PPF were effectively facilitated by 5Hz-rTMS. Additionally, the expressions of BDNF, SYP and NR2B were significantly increased via magnetic stimulation. The results suggest that rTMS considerably increases the expressions of BDNF, postsynaptic protein NR2B and presynaptic protein SYP, and thereby significantly enhances the synaptic plasticity and spatial cognition in normal animals. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Leptin-induced transphosphorylation of vascular endothelial growth factor receptor increases Notch and stimulates endothelial cell angiogenic transformation.

    Science.gov (United States)

    Lanier, Viola; Gillespie, Corey; Leffers, Merle; Daley-Brown, Danielle; Milner, Joy; Lipsey, Crystal; Webb, Nia; Anderson, Leonard M; Newman, Gale; Waltenberger, Johannes; Gonzalez-Perez, Ruben Rene

    2016-10-01

    Leptin increases vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2), and Notch expression in cancer cells, and transphosphorylates VEGFR-2 in endothelial cells. However, the mechanisms involved in leptin's actions in endothelial cells are not completely known. Here we investigated whether a leptin-VEGFR-Notch axis is involved in these leptin's actions. To this end, human umbilical vein and porcine aortic endothelial cells (wild type and genetically modified to overexpress VEGFR-1 or -2) were cultured in the absence of VEGF and treated with leptin and inhibitors of Notch (gamma-secretase inhibitors: DAPT and S2188, and silencing RNA), VEGFR (kinase inhibitor: SU5416, and silencing RNA) and leptin receptor, OB-R (pegylated leptin peptide receptor antagonist 2: PEG-LPrA2). Interestingly, in the absence of VEGF, leptin induced the expression of several components of Notch signaling pathway in endothelial cells. Inhibition of VEGFR and Notch signaling significantly decreased leptin-induced S-phase progression, proliferation, and tube formation in endothelial cells. Moreover, leptin/OB-R induced transphosphorylation of VEGFR-1 and VEGFR-2 was essential for leptin's effects. These results unveil for the first time a novel mechanism by which leptin could induce angiogenic features via upregulation/trans-activation of VEGFR and downstream expression/activation of Notch in endothelial cells. Thus, high levels of leptin found in overweight and obese patients might lead to increased angiogenesis by activating VEGFR-Notch signaling crosstalk in endothelial cells. These observations might be highly relevant for obese patients with cancer, where leptin/VEGFR/Notch crosstalk could play an important role in cancer growth, and could be a new target for the control of tumor angiogenesis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Combined Stimulation of IL-2 and 4-1BB Receptors Augments the Antitumor Activity of E7 DNA Vaccines by Increasing Ag-Specific CTL Responses

    Science.gov (United States)

    Kim, Ha; Kwon, Byungsuk; Sin, Jeong-Im

    2013-01-01

    Human papillomavirus (HPV) infection is a major cause of cervical cancer. Here, we investigate whether concurrent therapy using HPV E7 DNA vaccines (pE7) plus IL-2 vs. IL-15 cDNA and anti-4-1BB Abs might augment antitumor activity against established tumors. IL-2 cDNA was slightly better than IL-15 cDNA as a pE7 adjuvant. Co-delivery of pE7+IL-2 cDNA increased tumor cure rates from 7% to 27%, whereas co-delivery of pE7+IL-2 cDNA with anti-4-1BB Abs increased tumor cure rates from 27% to 67% and elicited long-term memory responses. This increased activity was concomitant with increased induction of Ag-specific CTL activity and IFN-γ responses, but not with Ag-specific IgG production. Moreover, the combined stimulation of IL-2 and 4-1BB receptors with rIL-2 and anti-4-1BB Abs resulted in enhanced production of IFN-γ from Ag-specific CD8+ T cells. However, this effect was abolished by treatment with anti-IL-2 Abs and 4-1BB-Fc, suggesting that the observed effect was IL-2- and anti-4-1BB Ab-specific. A similar result was also obtained for Ag-specific CTL activity. Thus, these studies demonstrate that combined stimulation through the IL-2 and 4-1BB receptors augments the Ag-specific CD8+ CTL responses induced by pE7, increasing tumor cure rates and long-term antitumor immune memory. These findings may have implications for the design of DNA-based therapeutic vaccines against cancer. PMID:24391824

  12. Increases in food intake or food-seeking behavior induced by GABAergic, opioid, or dopaminergic stimulation of the nucleus accumbens: is it hunger?

    Science.gov (United States)

    Hanlon, Erin C; Baldo, Brian A; Sadeghian, Ken; Kelley, Ann E

    2004-03-01

    Previous work has shown that stimulation of GABAergic, opioid, or dopaminergic systems within the nucleus accumbens modulates food intake and food-seeking behavior. However, it is not known whether such stimulation mimics a motivational state of food deprivation that commonly enables animals to learn a new operant response to obtain food. In order to address this question, acquisition of lever pressing for food in hungry animals was compared with acquisition in non-food-deprived rats subjected to various nucleus accumbens drug treatments. All animals were given the opportunity to learn an instrumental response (a lever press) to obtain a food pellet. Prior to training, ad lib-fed rats were infused with the gamma-aminobutyric acid (GABA)A agonist muscimol (100 ng/0.5 microl per side) or the mu-opioid receptor agonist D-Ala2, N-me-Phe4, Gly-ol5-enkephalin (DAMGO, 0.25 microg/0.5 microl per side), or saline into the nucleus accumbens shell (AcbSh). The indirect dopamine agonist amphetamine (10 microg/0.5 microl per side) was infused into the AcbSh or nucleus accumbens core (AcbC) of ad lib-fed rats. An additional group was food deprived and infused with saline in the AcbSh. Chow and sugar pellet intake responses after drug treatments were also evaluated in free-feeding tests. Muscimol, DAMGO, or amphetamine did not facilitate acquisition of lever pressing for food, despite clearly increasing food intake in free-feeding tests. In contrast, food-deprived animals rapidly learned the task. These findings suggest that pharmacological stimulation of any of these neurochemical systems in isolation is insufficient to enable acquisition of a food-reinforced operant task. Thus, these selective processes, while likely involved in control of food intake and food-seeking behavior, appear unable to recapitulate the conditions necessary to mimic the state of negative energy balance.

  13. Mangosteen leaf extract increases melanogenesis in B16F1 melanoma cells by stimulating tyrosinase activity in vitro and by up-regulating tyrosinase gene expression.

    Science.gov (United States)

    Hamid, Mariani Abdul; Sarmidi, Mohamad Roji; Park, Chang Seo

    2012-02-01

    Melanin synthesis is stimulated by various effectors, including α-melanocyte stimulating hormone (α-MSH), cyclic AMP (cAMP)-elevating agents (forskolin, isobutylmethylxantine, glycyrrhizin) and ultraviolet light. Our investigation focused on the identification of the melanogenic efficacy of mangosteen (Garcinia mangostana) leaf extract with regard to its effects on melanogenesis in B16F1 melanoma cells, since it has been known to possess strong anti-oxidant activities. The mangosteen leaf extract was found to stimulate melanin synthesis and tyrosinase activity in a dose-dependent manner without any significant effects on cell proliferation. Cytotoxicity of the extract was measured using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; the highest concentration of the extract that did not affect cell viability was 32 µg/ml. Formation of melanin from cultured B16F1 melanoma induced by extract treatment was estimated using spectrophotometry. In order to clarify the subsequent mechanism of tyrosinase activation by the extract, the levels of tyrosinase expression in B16F1 melanoma were examined using an intracellular tyrosinase assay and tyrosinase zymography. Up-regulation of intracellular tyrosinase expression seemed to correlate with an increase in microphtalmia-associated transcription factor (MITF) protein levels since MITF is the key factor for genes involved in melanogenesis. Both of the results showed that tyrosinase activity was markedly enhanced from extract-treated cells. The overall results suggest that mangosteen leaf extract may be a promising candidate for the treatment of hypopigmentation disorder and useful for self-tanning cosmetic products.

  14. Is abandonment of nonoperative management of hypertrophic pyloric stenosis warranted?

    Science.gov (United States)

    Lukac, Marija; Antunovic, Sanja Sindjic; Vujovic, Dragana; Pavicevic, Polina; Jesic, Milos; Krstajic, Tamara; Petronic, Ivana; Nikolic, Dejan

    2013-02-01

    Evaluation of the effectiveness of oral atropine versus surgical therapy for hypertrophic pyloric stenosis (HPS). A total of 66 consecutive patients with HPS were treated at the University Children's Hospital between January 2006 and December 2011. The diagnosis was initially based on medical history and confirmed by ultrasonography (US). The patients were divided into two groups according to the treatment preferred by their parents. The conservatively treated group, consisting of 33 boys and 7 girls, mean age 22.25 days, was given water-soluble atropine sulfate therapy at an initial dose of 0.05 mg/kg/day divided into 8 single doses, and administered after stomach decompression, 20 minutes prior to feeding. If vomiting persisted, the daily dose was progressively increased up to 0.18 mg/kg. If vomiting did not stop and full oral feeding was not reestablished in a week, surgery was done. The second group of 26 patients, mean age 20.86 days, underwent an operative procedure, Ramstedt extramucosal pyloromyotomy after the initial resuscitation. US evaluation was performed on days 7, 14, and 21. The outcome of the treatment was tested by Yates modification of the χ2 test. In the group of patients treated with atropine sulfate, 10 (25%) failed to respond to therapy, therefore, 8 boys and 2 girls underwent surgical treatment between the fifth and seventh day following institution of therapy. The remaining patients who received atropine sulfate (75%) were discharged when vomiting ceased, between the sixth and eighth day. They continued to take oral medication for 4 to 6 weeks, and were followed up by an ultrasound examination. The operated patients were discharged between the third and fifth day after surgery. There was a significant statistical difference between the groups regarding the outcome at a significance level of p < 0.05 (Yates χ2 = 5.839), with no complications regardless of the treatment option. However, at the significance level of p < 0.01 (Yates χ2 = 7

  15. Nuclear DNA content variation associated with muscle fiber hypertrophic growth in fishes.

    Science.gov (United States)

    Jimenez, Ana Gabriela; Kinsey, Stephen T

    2012-05-01

    Muscle fiber hypertrophic growth can lead to an increase in the myonuclear domain (MND), leading to greater diffusion distances within the cytoplasmic volume that each nucleus services. We tested the hypothesis that hypertrophic growth in the white muscle of fishes was associated with increases in the mean DNA content of nuclei, which may be a strategy to offset increasing diffusion constraints. DAPI-stained chicken erythrocytes standards and image analysis were used to estimate nuclear DNA content in erythrocytes and muscle fibers from 17 fish species. Mean diploid (2C) values in fish erythrocytes ranged from 0.78 to 7.2 pg. Erythrocyte 2C values were used to determine ploidy level in muscle tissue of small and large size classes of each species. Within each species, mean muscle fiber diameter was greater in the large size class than the small size class, and MND was significantly greater in larger fibers for 11 of the 17 species. Nuclear DNA content per species in muscle ranged from 2 to 64C. Fiber-size dependent increases in ploidy were observed in nine species, which is consistent with our hypothesis and indicates that endoreduplication is occurring during fiber growth. However, two species exhibited significantly lower ploidy in the larger size class, and the mechanistic basis and potential advantage of this ploidy shift is unclear. These results suggest that increases in ploidy may be a common mechanism to compensate for increases in MND associated with fiber hypertrophy in fishes, although it is likely that other factors also affect ploidy changes that occur in muscle during animal growth.

  16. Training-specific functional, neural, and hypertrophic adaptations to explosive- vs. sustained-contraction strength training.

    Science.gov (United States)

    Balshaw, Thomas G; Massey, Garry J; Maden-Wilkinson, Thomas M; Tillin, Neale A; Folland, Jonathan P

    2016-06-01

    Training specificity is considered important for strength training, although the functional and underpinning physiological adaptations to different types of training, including brief explosive contractions, are poorly understood. This study compared the effects of 12 wk of explosive-contraction (ECT, n = 13) vs. sustained-contraction (SCT, n = 16) strength training vs. control (n = 14) on the functional, neural, hypertrophic, and intrinsic contractile characteristics of healthy young men. Training involved 40 isometric knee extension repetitions (3 times/wk): contracting as fast and hard as possible for ∼1 s (ECT) or gradually increasing to 75% of maximum voluntary torque (MVT) before holding for 3 s (SCT). Torque and electromyography during maximum and explosive contractions, torque during evoked octet contractions, and total quadriceps muscle volume (QUADSVOL) were quantified pre and post training. MVT increased more after SCT than ECT [23 vs. 17%; effect size (ES) = 0.69], with similar increases in neural drive, but greater QUADSVOL changes after SCT (8.1 vs. 2.6%; ES = 0.74). ECT improved explosive torque at all time points (17-34%; 0.54 ≤ ES ≤ 0.76) because of increased neural drive (17-28%), whereas only late-phase explosive torque (150 ms, 12%; ES = 1.48) and corresponding neural drive (18%) increased after SCT. Changes in evoked torque indicated slowing of the contractile properties of the muscle-tendon unit after both training interventions. These results showed training-specific functional changes that appeared to be due to distinct neural and hypertrophic adaptations. ECT produced a wider range of functional adaptations than SCT, and given the lesser demands of ECT, this type of training provides a highly efficient means of increasing function. Copyright © 2016 the American Physiological Society.

  17. Children's exposure to violent political conflict stimulates aggression at peers by increasing emotional distress, aggressive script rehearsal, and normative beliefs favoring aggression.

    Science.gov (United States)

    Huesmann, L Rowell; Dubow, Eric F; Boxer, Paul; Landau, Simha F; Gvirsman, Shira Dvir; Shikaki, Khalil

    2017-02-01

    We examine the hypothesis that children's exposure to ethnic-political conflict and violence over the course of a year stimulates their increased aggression toward their own in-group peers in subsequent years. In addition, we examine what social cognitive and emotional processes mediate these effects and how these effects are moderated by gender, age, and ethnic group. To accomplish these aims, we collected three waves of data from 901 Israeli and 600 Palestinian youths (three age cohorts: 8, 11, and 14 years old) and their parents at 1-year intervals. Exposure to ethnic-political violence was correlated with aggression at in-group peers among all age cohorts. Using a cross-lagged structural equation model from Year 1 to Year 3, we found that the relation between exposure and aggression is more plausibly due to exposure to ethnic-political violence stimulating later aggression at peers than vice versa, and this effect was not moderated significantly by gender, age cohort, or ethnic group. Using three-wave structural equation models, we then showed that this effect was significantly mediated by changes in normative beliefs about aggression, aggressive script rehearsal, and emotional distress produced by the exposure. Again the best fitting model did not allow for moderation by gender, age cohort, or ethnic group. The findings are consistent with recent theorizing that exposure to violence leads to changes both in emotional processes promoting aggression and in the acquisition through observational learning of social cognitions promoting aggression.

  18. Topical Calcipotriol for Preventive Treatment of Hypertrophic Scars A Randomized, Double-blind, Placebo-Controlled Trial

    NARCIS (Netherlands)

    van der Veer, Willem M.; Jacobs, Xander E.; Waardenburg, Ingmar E.; Ulrich, Magda M.; Niessen, Frank B.

    2009-01-01

    Objectives: To evaluate the efficacy of topical application of calcipotriol to healing wounds in preventing or reducing hypertrophic scar formation and to investigate the biochemical properties of the epidermis associated with hypertrophic scar formation. Design: Randomized, double-blind,

  19. Topical Calcipotriol for Preventive Treatment of Hypertrophic Scars A Randomized, Double-blind, Placebo-Controlled Trial

    NARCIS (Netherlands)

    van der Veer, Willem M.; Jacobs, Xander E.; Waardenburg, Ingmar E.; Ulrich, Magda M.; Niessen, Frank B.

    2009-01-01

    Objectives: To evaluate the efficacy of topical application of calcipotriol to healing wounds in preventing or reducing hypertrophic scar formation and to investigate the biochemical properties of the epidermis associated with hypertrophic scar formation. Design: Randomized, double-blind,

  20. Increasing palmitic acid intake enhances milk production and prevents glucose-stimulated fatty acid disappearance without modifying systemic glucose tolerance in mid-lactation dairy cows.

    Science.gov (United States)

    Mathews, A T; Rico, J E; Sprenkle, N T; Lock, A L; McFadden, J W

    2016-11-01

    first week of PALM treatment; however, glucose disposal following glucose tolerance tests was not modified. In contrast, C16:0 feeding reduced glucose-stimulated NEFA disappearance by wk 7. Results demonstrate that increasing dietary energy from C16:0 for 7wk improves milk yield and milk composition without modifying systemic glucose tolerance. Reduced glucose-stimulated NEFA disappearance with C16:0 feeding and elevated circulating NEFA may reflect changes in adipose tissue insulin sensitivity. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  1. Exercise training favors increased insulin-stimulated glucose uptake in skeletal muscle in contrast to adipose tissue: a randomized study using FDG PET imaging

    DEFF Research Database (Denmark)

    Reichkendler, M. H.; Auerbach, P.; Rosenkilde, M.

    2013-01-01

    Physical exercise increases peripheral insulin sensitivity, but regional differences are poorly elucidated in humans. We investigated the effect of aerobic exercise training on insulin-stimulated glucose uptake in five individual femoral muscle groups and four different adipose tissue regions...... was highest in femoral skeletal muscle followed by intraperitoneal visceral adipose tissue (VAT), retroperitoneal VAT, abdominal (anterior + posterior) subcutaneous adipose tissue (SAT), and femoral SAT (P ... groups in femoral skeletal muscle (MOD 24[9, 39] μmol·kg−1·min−1, P = 0.004; HIGH 22[9, 35] μmol·kg−1·min−1, P = 0.003) (mean[95% CI]) and in five individual femoral muscle groups but not in femoral SAT. Standardized uptake value of FDG decreased ∼24% in anterior abdominal SAT and ∼20% in posterior...

  2. Carriers of a VEGFA enhancer polymorphism selectively binding CHOP/DDIT3 are predisposed to increased circulating levels of thyroid-stimulating hormone

    DEFF Research Database (Denmark)

    Ahluwalia, Tarun Veer Singh; Troelsen, Jesper Thorvald; Balslev-Harder, Marie

    2017-01-01

    BACKGROUND: Levels of serum thyroid-stimulating hormone (TSH) indicate thyroid function, because thyroid hormone negatively controls TSH release. Genetic variants in the vascular endothelial growth factor A (VEGFA) gene are associated with TSH levels. The aim of this study was to characterise...... the association of VEGFA variants with TSH in a Danish cohort and to identify and characterise functional variants. METHODS: We performed an association study of the VEGFA locus for circulating TSH levels in 8445 Danish individuals. Lead variants were tested for allele-specific effects in vitro using luciferase...... reporter and gel-shift assays. RESULTS: Four SNPs in VEGFA were associated with circulating TSH (rs9472138, rs881858, rs943080 and rs4711751). For rs881858, the presence of each G-allele was associated with a corresponding decrease in TSH levels of 2.3% (p=8.4×10(-9)) and an increase in circulating free T4...

  3. Diammonium phosphate stimulates transcription of L-lactate dehydrogenase leading to increased L-lactate production in the thermotolerant Bacillus coagulans strain.

    Science.gov (United States)

    Sun, Lifan; Li, Yanfeng; Wang, Limin; Wang, Yanping; Yu, Bo

    2016-08-01

    Exploration of cost-effective fermentation substrates for efficient lactate production is an important economic objective. Although some organic nitrogen sources are also cheaper, inorganic nitrogen salts for lactate fermentation have additional advantages in facilitating downstream procedures and significantly improving the commercial competitiveness of lactate production. In this study, we first established an application of diammonium phosphate to replace yeast extract with a reduced 90 % nitrogen cost for a thermotolerant Bacillus coagulans strain. In vivo enzymatic and transcriptional analyses demonstrated that diammonium phosphate stimulates the gene expression of L-lactate dehydrogenase, thus providing higher specific enzyme activity in vivo and increasing L-lactic acid production. This new information provides a foundation for establishing a cost-effective process for polymer-grade L-lactic acid production in an industrial setting.

  4. Two weeks of moderate-intensity continuous training, but not high-intensity interval training, increases insulin-stimulated intestinal glucose uptake.

    Science.gov (United States)

    Motiani, Kumail K; Savolainen, Anna M; Eskelinen, Jari-Joonas; Toivanen, Jussi; Ishizu, Tamiko; Yli-Karjanmaa, Minna; Virtanen, Kirsi A; Parkkola, Riitta; Kapanen, Jukka; Grönroos, Tove J; Haaparanta-Solin, Merja; Solin, Olof; Savisto, Nina; Ahotupa, Markku; Löyttyniemi, Eliisa; Knuuti, Juhani; Nuutila, Pirjo; Kalliokoski, Kari K; Hannukainen, Jarna C

    2017-05-01

    Similar to muscles, the intestine is also insulin resistant in obese subjects and subjects with impaired glucose tolerance. Exercise training improves muscle insulin sensitivity, but its effects on intestinal metabolism are not known. We studied the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on intestinal glucose and free fatty acid uptake from circulation in humans. Twenty-eight healthy, middle-aged, sedentary men were randomized for 2 wk of HIIT or MICT. Intestinal insulin-stimulated glucose uptake and fasting free fatty acid uptake from circulation were measured using positron emission tomography and [ 18 F]FDG and [ 18 F]FTHA. In addition, effects of HIIT and MICT on intestinal GLUT2 and CD36 protein expression were studied in rats. Training improved aerobic capacity ( P = 0.001) and whole body insulin sensitivity ( P = 0.04), but not differently between HIIT and MICT. Insulin-stimulated glucose uptake increased only after the MICT in the colon (HIIT = 0%; MICT = 37%) ( P = 0.02 for time × training) and tended to increase in the jejunum (HIIT = -4%; MICT = 13%) ( P = 0.08 for time × training). Fasting free fatty acid uptake decreased in the duodenum in both groups (HIIT = -6%; MICT = -48%) ( P = 0.001 time) and tended to decrease in the colon in the MICT group (HIIT = 0%; MICT = -38%) ( P = 0.08 for time × training). In rats, both training groups had higher GLUT2 and CD36 expression compared with control animals. This study shows that already 2 wk of MICT enhances insulin-stimulated glucose uptake, while both training modes reduce fasting free fatty acid uptake in the intestine in healthy, middle-aged men, providing an additional mechanism by which exercise training can improve whole body metabolism. NEW & NOTEWORTHY This is the first study where the effects of exercise training on the intestinal substrate uptake have been investigated using the most advanced techniques

  5. Hypertrophic scars after therapy with CO2 laser for treatment of multiple cutaneous neurofibromas

    NARCIS (Netherlands)

    J.U. Ostertag (Judith); C.C.W. Theunissen (Chantal); H.A.M. Neumann (Martino)

    2002-01-01

    textabstractBACKGROUND. CO2 laser surgery is a treatment modality for cutaneous neurofibromas. OBJECTIVE. Hypertrophic and atrophic scars can result from treatment with CO2 laser surgery. We present a case of cutaneous neurofibromatosis that developed hypertrophic scars postoperatively. METHODS.

  6. Survival and sudden cardiac death after septal ablation for hypertrophic obstructive cardiomyopathy

    DEFF Research Database (Denmark)

    Jensen, Morten Kvistholm; Havndrup, Ole; Hassager, Christian

    2011-01-01

    Reports of long-term survival and the risk of sudden cardiac death (SCD) after percutaneous transluminal septal myocardial ablation (PTSMA) in patients with hypertrophic obstructive cardiomyopathy (HOCM) are sparse.......Reports of long-term survival and the risk of sudden cardiac death (SCD) after percutaneous transluminal septal myocardial ablation (PTSMA) in patients with hypertrophic obstructive cardiomyopathy (HOCM) are sparse....

  7. Influence of Septal Thickness on the Clinical Outcome After Alcohol Septal Alation in Hypertrophic Cardiomyopathy

    DEFF Research Database (Denmark)

    Jensen, Morten K; Jacobsson, Linda; Almaas, Vibeke Marie

    2016-01-01

    BACKGROUND: We assessed the influence of interventricular septal thickness (IVSd) on the clinical outcome and survival after alcohol septal ablation (ASA) in patient with hypertrophic cardiomyopathy. METHODS AND RESULTS: We analyzed 531 patients with hypertrophic cardiomyopathy (age: 56±14 years...

  8. HYPERTROPHIC CARDIOMYOPATHY AS A PART OF INHERITED MALFORMATION SYNDROMES IN INFANTS

    Directory of Open Access Journals (Sweden)

    M.V. Tural'chuk

    2011-01-01

    Full Text Available The data of clinical and instrumental examination of two infantile patients with obstructive hypertrophic cardiomyopathy in association with marked multisystem involvement as a picture of inherited malformation syndromes are given.Key words: infants, hypertrophic cardiomyopathy, LEOPARD syndrome, Noonan syndrome.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2011; 10 (3: 166–169

  9. Outcome of Alcohol Septal Ablation in Mildly Symptomatic Patients With Hypertrophic Obstructive Cardiomyopathy

    DEFF Research Database (Denmark)

    Veselka, Josef; Faber, Lothar; Liebregts, Max

    2017-01-01

    BACKGROUND: The long-term efficacy and safety of alcohol septal ablation (ASA) in patients with highly symptomatic hypertrophic obstructive cardiomyopathy has been demonstrated. The aim of this study was to evaluate the long-term outcomes of mildly symptomatic patients with hypertrophic obstructive...

  10. Collecting, Analyzing, and Publishing Massive Data about the Hypertrophic Cardiomyopathy

    Science.gov (United States)

    Montserrat, Lorenzo; Cotelo-Lema, Jose Antonio; Luaces, Miguel R.; Seco, Diego

    We present in this paper the architecture and some implementation details of a Document Management System and Workflow to help in the diagnosis of the hypertrophic cardiomyopathy, one of the most frequent genetic cardiovascular diseases. The system allows a gradual and collaborative creation of a knowledge base about the mutations associated with this disease. The system manages both the original documents of the scientific papers and the data extracted from these papers by the experts. Furthermore, a semiautomatic report generation module exploits this knowledge base to create high quality reports about the studied mutations.

  11. [Hypertrophic pyloric stenosis. Review of 314 cases (author's transl)].

    Science.gov (United States)

    De Jaureguizar, E; Cabrera, R; Herrero, E; Monereo, J

    1978-04-01

    Three hundred fourteen patients with hypertrophic pyloric stenosis have been operated from 1969 to 1976. The different etiologies are discussed. Clinical and analytical data are evaluated. Radiology is employed in 99 per 100 of the cases with no complications. Medical treatment used is exposed clearly as well as the surgical procedure (Monereo's modification of the classical Fredet-Ramstedt technique). Postoperative results and complications such as vomiting, wound infection (4.4 per 100), eventration (0.6 per 100) and fatal outcome (0.6 per 100) are thouroughly detailed as well as the associated pathology.

  12. Lung carcinoma with hypertrophic osteoarthropathy in a teenager

    Directory of Open Access Journals (Sweden)

    Jeremy Whelan

    2011-03-01

    Full Text Available Hypertrophic osteoarthropathy (HOA characterised by arthralgia, clubbing and periosteal proliferation of long bones, is rarely encountered in children and adolescents. Whereas in adults over 80% of cases are associated with malignancy, in children the majority of cases are due to non-neoplastic causes such as cystic fibrosis, bilary atresia and congenital heart disease. Up to 5% of adults with lung cancer demonstrate signs of HOA. However, lung cancer is extremely uncommon in children and young people. Here we report a case of lung adenocarcinoma in an 18 year old male associated with HOA present both at diagnosis and at subsequent disease progression.

  13. FACTORS INFLUENCING THE OCCURRENCE OF HYPERTROPHIC SCARS AMONG POSTOPERATIVE PATIENTS IN GARUT, INDONESIA

    Directory of Open Access Journals (Sweden)

    Andri Nugraha

    2017-02-01

    Full Text Available Background: Hypertrophic scar causes physical and psychological problems. Thus understanding the factors related to the occurrence of hypertrophic scar tissue is needed. Little is known about its influencing factors in Indonesia, especially in Garut. Objective: This study aims to examine the relationships between hypertrophic scar and its influencing factors, and identify the most dominant factor of the occurrence of hypertrophic scars. Methods: This was an observational case control study using retrospective approach in Polyclinic of Surgery of Regional Public Hospital of dr. Slamet of Garut Regency. There were 40 samples recruited in this study by purposive sampling, which was divided to be case group (20 patients and control group (20 patients. Data were collected using Stony Brook Scar Evaluation Scale by observation and documentation of the medical records of patients. Data were analyzed using logistic regression analysis Results: Findings indicated that there were significant relationships between the surgical wound infection (p = 0.02, family history (p = 0.026, and type of suture (p = 0.043 with the occurrence of hypertrophic scars. The most dominant factor on the occurrence of hypertrophic scars was type of suture, acid polyglactin 910. The variables that had no significant relationships with the occurrence of hypertrophic scar tissue were age (p = 0.34, area of surgical wound (p = 0.177, and smoking habit (p = 0.479. Conclusion: There were significant relationships between infection of surgical wound, genetic history, the type of suture, and the occurrence of hypertrophic scar tissue. The most dominant factor that influenced the occurrence of hypertrophic scar tissue was the type of suture. Therefore, it is suggested to health professionals to modify the using of acid polyglactin 910 sutures, and nurses particularly need to provide the information regarding the family history and genetic-related hypertrophic scar, and prevent the

  14. A soluble granulocyte colony stimulating factor decoy receptor as a novel tool to increase hematopoietic cell homing and reconstitution in mice.

    Science.gov (United States)

    Fortin, Audrey; Benabdallah, Basma; Palacio, Lina; Carbonneau, Cynthia L; Le, Oanh N; Haddad, Elie; Beauséjour, Christian M

    2013-03-15

    The relative ineffectiveness of hematopoietic stem cells in reaching the bone marrow upon transplantation combined with the limited number of these cells available is a major reason for graft failure and delayed hematopoietic recovery. Hence, the development of strategies that could enhance homing is of high interest. Here, we provide evidence that homing is severely impaired postexposure to ionizing radiation (IR) in mice, an effect we found was time dependent and could be partially rescued using mesenchymal stromal cell (MSC) therapy. In an attempt to further increase homing, we took advantage of our observation that the granulocyte colony stimulating factor (G-CSF), a cytokine known to induce cell mobilization, is increased in the marrow of mice shortly after their exposure to IR. As such, we developed a truncated, yet functional, soluble G-CSF receptor (solG-CSFR), which we hypothesized could act as a decoy and foster homing. Using MSCs or conditioned media as delivery vehicles, we show that an engineered solG-CSFR has the potential to increase homing and hematopoietic reconstitution in mice. Altogether, our results provide novel findings at the interplay of IR and stromal cell therapy and present the regulation of endogenous G-CSF as an innovative proof-of-concept strategy to manipulate hematopoietic cell homing.

  15. Increase in body weight is a non-motor side effect of deep brain stimulation of the subthalamic nucleus in Parkinson's disease.

    Science.gov (United States)

    Novakova, Lucie; Ruzicka, Evzen; Jech, Robert; Serranova, Tereza; Dusek, Petr; Urgosik, Dusan

    2007-02-01

    Deep brain stimulation of the subthalamic nucleus (DBS STN) is an effective treatment method in advanced Parkinson's disease (PD) providing marked improvement of its major motor symptoms. In addition, non-motor effects have been reported including weight gain in PD patients after DBS STN. Using retrospective survey, we aimed to evaluate weight changes in our patients with advanced PD treated with DBS STN. We inquired 25 PD patients (16 men, 9 women), of mean age 55 (42-65) years, mean PD duration 15 (9-21) years, who previously received bilateral DBS STN. We obtained valid data from 23 patients. In the first survey, 1 to 45 months after DBS, weight gain was found in all patients comparing to pre-DBS period. The mean increase was 9.4 kg (from 1 to 25 kg). The patients' mean body mass index (BMI) increased from 23.7 to 27.0 kg/m2, i.e. by 3.3 kg/m2 (+2 to +6.1 kg/m2). In the repeated survey one year later, in 12 of the patients body weight moderately decreased, 3 did not change, and 6 patients further increased their weight. Possible explanations of body weight gain after DBS STN include a reduction of energy output related to elimination of dyskinesias, improved alimentation or direct influence on function of lateral hypothalamus by DBS STN.

  16. Granulocyte-Colony Stimulating Factor Increases Cerebral Blood Flow via a NO Surge Mediated by Akt/eNOS Pathway to Reduce Ischemic Injury

    Directory of Open Access Journals (Sweden)

    Hock-Kean Liew

    2015-01-01

    Full Text Available Granulocyte-colony stimulating factor (G-CSF protects brain from ischemic/reperfusion (I/R injury, and inhibition of nitric oxide (NO synthases partially reduces G-CSF protection. We thus further investigated the effects of G-CSF on ischemia-induced NO production and its consequence on regional cerebral blood flow (rCBF and neurological deficit. Endothelin-1 (ET-1 microinfused above middle cerebral artery caused a rapid reduction of rCBF (ischemia which lasted for 30 minutes and was followed by a gradual recovery of blood flow (reperfusion within the striatal region. Regional NO concentration increased rapidly (NO surge during ischemia and recovered soon to the baseline. G-CSF increased rCBF resulting in shorter ischemic duration and an earlier onset of reperfusion. The enhancement of the ischemia-induced NO by G-CSF accompanied by elevation of phospho-Akt and phospho-eNOS was noted, suggesting an activation of Akt/eNOS. I/R-induced infarct volume and neurological deficits were also reduced by G-CSF treatment. Inhibition of NO synthesis by L-NG-Nitroarginine Methyl Ester (L-NAME significantly reduced the effects of G-CSF on rCBF, NO surge, infarct volume, and neurological deficits. We conclude that G-CSF increases rCBF through a NO surge mediated by Akt/eNOS, which partially contributes to the beneficial effect of G-CSF on brain I/R injury.

  17. Consumption of selenium-enriched broccoli increases cytokine production in human peripheral blood mononuclear cells stimulated ex vivo, a preliminary human intervention study.

    Science.gov (United States)

    Bentley-Hewitt, Kerry L; Chen, Ronan K-Y; Lill, Ross E; Hedderley, Duncan I; Herath, Thanuja D; Matich, Adam J; McKenzie, Marian J

    2014-12-01

    Selenium (Se) is a micronutrient essential for human health, including immune function. Previous research indicates that Se supplementation may cause a shift from T helper (Th)1- to Th2-type immune responses. We aim to test the potential health promoting effects of Se-enriched broccoli. In a human trial, 18 participants consumed control broccoli daily for 3 days. After a 3-day wash-out period, the participants were provided with Se-enriched broccoli containing 200 μg of Se per serving for 3 days. Plasma and peripheral blood mononuclear cell (PBMC) samples were collected at the start and end of each broccoli feeding period for analysis of total Se and measurement of cytokine production from PBMC stimulated with antigens ex vivo. Plasma Se content remained consistent throughout the control broccoli feeding period and the baseline of the Se-enriched broccoli period (1.22 μmol/L) and then significantly increased following 3 days of Se-enriched broccoli feeding. Interleukin (IL-2, IL-4, IL-5, IL-13, and IL-22) production from PBMC significantly increased after 3 days of Se-enriched broccoli feeding compared with baseline. This study indicates that consumption of Se-enriched broccoli may increase immune responses toward a range of immune challenges. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Noradrenaline increases intracellular glutathione in human astrocytoma U-251 MG cells by inducing glutamate-cysteine ligase protein via β3-adrenoceptor stimulation.

    Science.gov (United States)

    Yoshioka, Yasuhiro; Kadoi, Hisatsugu; Yamamuro, Akiko; Ishimaru, Yuki; Maeda, Sadaaki

    2016-02-05

    Glutathione (GSH) plays a critical role in protecting cells from oxidative damage. Since neurons rely on the supply of GSH from astrocytes to maintain optimal intracellular GSH concentrations, the GSH concentration of astrocytes is important for the survival of neighboring neurons against oxidative stress. The neurotransmitter noradrenaline is known to modulate the functions of astrocytes and has been suggested to have neuroprotective properties in neurodegenerative diseases. To elucidate the mechanisms underlying the neuroprotective properties of noradrenaline, in this study, we investigated the effect of noradrenaline on the concentrations of intracellular GSH in human U-251 malignant glioma (MG; astrocytoma) cells. Treatment of the cells with noradrenaline for 24h concentration-dependently increased their intracellular GSH concentration. This increase was inhibited by a non-selective β-adrenoceptor antagonist propranolol and by a selective β3-adrenoceptor antagonist SR59230A, but not by a non-selective α-adrenoceptor antagonist phenoxybenzamine, or by a selective β1-adrenoceptor antagonist atenolol or by a selective β2-adrenoceptor antagonist butoxamine. In addition, the selective β3-adrenoceptor agonist CL316243 increased the intracellular GSH in U-251 MG cells. Treatment of the cells with noradrenaline (10μM) for 24h increased the protein level of the catalytic subunit of glutamate-cysteine ligase (GCLc), the rate-limiting enzyme of GSH synthesis; and this increase was inhibited by SR59230A. These results thus suggest that noradrenaline increased the GSH concentration in astrocytes by inducing GCLc protein in them via β3-adrenoceptor stimulation. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Isolated papillary muscle hypertrophy: A gap in our knowledge of hypertrophic cardiomyopathy?

    Science.gov (United States)

    Ferreira, Catarina; Delgado, Carlos; Vázquez, María; Trinidad, Carmen; Vilar, Manuel

    2014-06-01

    Increased thickness of left ventricular walls is the predominant characteristic and one of the diagnostic criteria of hypertrophic cardiomyopathy (HCM). This case illustrates an uncommon but important finding of isolated hypertrophy of the papillary muscles (PMs), observed in a young woman in whom an abnormal electrocardiogram was initially detected. During the investigation isolated PM hypertrophy was identified. The structural characteristics of the PMs have received scant attention in this setting and there is little information in the literature on this entity, whose real prevalence and clinical significance remain to be determined. The available information relates solitary PM hypertrophy with an early form or a different pattern of HCM. In this case PM hypertrophy was only detected due to the finding of an abnormal electrocardiogram, which prompted further diagnostic tests and a search for possible etiologies. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  20. Increased enzymatic hydrolysis of sugarcane bagasse by a novel glucose- and xylose-stimulated β-glucosidase from Anoxybacillus flavithermus subsp. yunnanensis E13T.

    Science.gov (United States)

    Liu, Yang; Li, Rui; Wang, Jing; Zhang, Xiaohan; Jia, Rong; Gao, Yi; Peng, Hui

    2017-03-16

    β-Glucosidase is claimed as a key enzyme in cellulose hydrolysis. The cellulosic fibers are usually entrapped with hemicelluloses containing xylose. So there is ongoing interest in searching for glucose- and xylose-stimulated β-glucosidases to increase the efficiency of hydrolysis of cellulosic biomass. A thermostable β-glucosidase gene (Bglp) was cloned from Anoxybacillus flavithermus subsp. yunnanensis E13T and characterized. Optimal enzyme activity was observed at 60 °C and pH 7.0. Bglp was relatively stable at 60 °C with a 10-h half-life. The kinetic parameters V max and K m for p-nitrophenyl-β-D-glucopyranoside (pNPG) were 771 ± 39 μmol/min/mg and 0.29 ± 0.01 mM, respectively. The activity of Bglp is dramatically stimulated by glucose or xylose at concentrations up to 1.4 M. After Bglp was added to Celluclast® 1.5 L, the conversion of sugarcane bagasse was 48.4 ± 0.8%, which was much higher than of Celluclast® 1.5 L alone. Furthermore, Bglp showed obvious advantages in the hydrolysis when initial concentrations of glucose and xylose are high. The supplementation of BglP significantly enhanced the glucose yield from sugarcane bagasse, especially in the presence of high concentrations of glucose or xylose. Bglp should be a promising candidate for industrial applications.

  1. Colony stimulating factor-1 and leukemia inhibitor factor expression from current-cycle cannula isolated endometrial cells are associated with increased endometrial receptivity and pregnancy.

    Science.gov (United States)

    Camargo-Díaz, Felipe; García, Valeria; Ocampo-Bárcenas, Azucena; González-Marquez, Humberto; López-Bayghen, Esther

    2017-08-22

    Poor endometrial quality is associated with more than a third of embryo implantation failures. Current ultrasonography technology lacks the capacity to determine efficiently the endometrial receptivity during ongoing cycle transfers. We analyzed the relationship between the gene expression profile associated with implantation and clinical pregnancy from endometrial cells taken during embryo transfer. Seventy-six patients submitted to a standard ovarian stimulation protocol, in vitro fertilization, and good quality embryos were collected (morphological assessment). Endometrial samples were taken with ultrasonography guidance and cells were Hematoxylin and Eosin stained for morphological identification. Total RNA was extracted and the expression of Mucin 1 (MUC1), Homeobox A10 (HOXA-10), Leukemia Inhibitor Factor (LIF), Colony Stimulating Factor-1 (CSF-1), and ribosomal 18 s (endogenous control) were analyzed using RT-qPCR. Presence of a gestational sac, β-hGC (≥10 mIU/mL on Day 20), and a fetal heartbeat were used to determine a positive embryo implantation and pregnancy. Samples collected from same cycle embryo transfer showed clear morphological staining for endometrial cells (80-90% of the cells). Cells in the sample were molecularly identified as the endometrium (HOXA-10 positive and MUC-1 negative). CSF-1 expression was 4.55-fold and LIF expression was 12.25-fold higher in patients who became pregnant. Both increases were statistically significant (p endometrial receptivity. Furthermore, we demonstrate that the expression profile, based on LIF and CSF-1, showed a difference between a receptive and a non-receptive endometrium.

  2. Postexercise hypertrophic adaptations: a reexamination of the hormone hypothesis and its applicability to resistance training program design.

    Science.gov (United States)

    Schoenfeld, Brad J

    2013-06-01

    It has been well documented in the literature that resistance training can promote marked increases in skeletal muscle mass. Postexercise hypertrophic adaptations are mediated by a complex enzymatic cascade whereby mechanical tension is molecularly transduced into anabolic and catabolic signals that ultimately lead to a compensatory response, shifting muscle protein balance to favor synthesis over degradation. Myocellular signaling is influenced, in part, by the endocrine system. Various hormones have been shown to alter the dynamic balance between anabolic and catabolic stimuli in muscle, helping to mediate an increase or decrease in muscle protein accretion. Resistance training can have an acute impact on the postexercise secretion of several of these hormones including insulin-like growth factor, testosterone, and growth hormone (GH). Studies show that hormonal spikes are magnified after hypertrophy-type exercise that involves training at moderate intensities with shortened rest intervals as compared with high-intensity strength-oriented training. The observed positive relationship between anabolic hormones and hypertrophy-type training has led to the hormone hypothesis, which postulates that acute postexercise hormonal secretions mediate increases in muscle size. Several researchers have suggested that these transient hormonal elevations may be more critical to hypertrophic adaptations than chronic changes in resting hormonal concentrations. Theoretically, high levels of circulating hormones increase the likelihood of interaction with receptors, which may have particular hypertrophic importance in the postworkout period when muscles are primed for anabolism. Moreover, hormonal spikes may enhance intracellular signaling so that postexercise protein breakdown is rapidly attenuated and anabolic processes are heightened, thereby leading to a greater supercompensatory response. Although the hormone hypothesis has received considerable support in the literature

  3. Scintigraphic evaluation of regional myocardial sympathetic activity in patients with hypertrophic cardiomyopathy. Comparison between asymmetrical hypertrophic cardiomyopathy and apical hypertrophy

    Energy Technology Data Exchange (ETDEWEB)

    Eno, Shin; Takeo, Eiichiro; Sasaki, Satoshi; Matsuda, Keiji; Fujii, Hideaki; Kanazawa, Ikuo [Chugoku Rosai General Hospital, Kure, Hiroshima (Japan)

    1998-02-01

    Using {sup 123}I-MIBG (metaiodobenzylguanidine) and {sup 201}Tl imagings, an examination concerning the relation between the hypertrophic region and its sympathetic nervous function was done. Subjects were 12 normal adults (4 males and 8 females, mean age 61.3 yr), 13 patients with asymmetrical hypertrophic cardiomyopathy (10 males and 3 females, 63.9 yr) and 13 patients with apical hypertrophy (9 males and 4 females, 67.2 yr). The SPECT apparatus was Toshiba two-gated gamma camera GCA 7200A. At 20 min and 3 hr after intravenous injection of 111 MBq of {sup 123}I-MIBG, myocardial SPECT and planar images were obtained with collimator LEHR under following conditions: photoelectric peak 159 KeV, window width 20%, matrix size 64 x 64 (256 x 256 for the planar image), step angle 6deg, 40 sec/step and 180deg for 1 camera. In another day, {sup 201}Tl SPECT and planar imagings were performed 10 min after intravenous injection of 111 MBq of {sup 201}Tl for the photoelectric peak 72 KeV under similar conditions to above. SPECT images were reconstructed using Butterworth filter and Shepp and Logan filter. Images were examined for the defect score, myocardium/mediastinum ratio, whole heart washout rate and regional washout rate. In the asymmetrical hypertrophic myopathy, abnormal sympathetic nerve function was recognized on the regions regardless of their disease severity while in the apical hypertrophy, abnormality was restricted on the apical region. Therefore, the two diseases were found different from each other from the aspect of sympathetic nerve functions. (K.H.)

  4. Molecular mechanisms of gallic acid-induced growth inhibition, apoptosis, and necrosis in hypertrophic scar fibroblasts.

    Science.gov (United States)

    Hsieh, Shu-Chung; Wu, Chun-Chi; Hsu, Shih-Lan; Yen, Jung-Hsing

    2017-06-15

    To explore the effect and molecular mechanism of gallic acid (GA) on the cytostatic and cytotoxicity of hypertrophic scar fibroblasts (HSFs). HSFs were treated with a serial dose of GA for indicated time. The cytostatic and cytotoxicity of GA were evaluated by microscopy, trypan blue exclusion assay and LDH releasing. The mechanisms of GA-induced cytostatic were examined by cell cycle distribution assay and the expression of cell cycle-relative protein. GA-elicited apoptosis were verified by TUNEL assay, mitochondria membrane potential, caspase activity and the expression of apoptosis-relative protein. GA-induced necrosis was confirmed by lysosome rupture using acridine orange stain. Various blockers, including intracellular calcium chelator; BAPTA-AM, IP3R blocker; 2-APB, calpain inhibitor, ALLM and ALLN were used to address the signaling cascade in GA-induced HSF necrosis. GA-induced growth inhibition, apoptosis, and necrosis in HSFs depend on increasing dose. HSFs treated with GA at non-cytotoxic concentrations (50 to 75μM) significant increased both the S- and G2/M-phase HSFs population, and this event was accompanied with down-regulation of cyclin A, cyclin B, CDK1 and CDK2. Incubation of HSFs with 100-150μM of GA induced apoptosis through Bcl2/Bax-mitochondrial-dependent pathway. While the concentrations up to 200μM of GA that elicited necrosis via a calcium/calpain I/lysosome rupture signaling axis. Interestingly, GA at 200μM did not harm to keratinocyte. These results revealed that GA might have the potential to be developed as a treatment for patients with hypertrophic scar. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Pathogenesis of depression- and anxiety-like behavior in an animal model of hypertrophic cardiomyopathy.

    Science.gov (United States)

    Dossat, Amanda M; Sanchez-Gonzalez, Marcos A; Koutnik, Andrew P; Leitner, Stefano; Ruiz, Edda L; Griffin, Brittany; Rosenberg, Jens T; Grant, Samuel C; Fincham, Francis D; Pinto, Jose R; Kabbaj, Mohamed

    2017-06-01

    Cardiovascular dysfunction is highly comorbid with mood disorders, such as anxiety and depression. However, the mechanisms linking cardiovascular dysfunction with the core behavioral features of mood disorder remain poorly understood. In this study, we used mice bearing a knock-in sarcomeric mutation, which is exhibited in human hypertrophic cardiomyopathy (HCM), to investigate the influence of HCM over the development of anxiety and depression. We employed behavioral, MRI, and biochemical techniques in young (3-4 mo) and aged adult (7-8 mo) female mice to examine the effects of HCM on the development of anxiety- and depression-like behaviors. We focused on females because in both humans and rodents, they experience a 2-fold increase in mood disorder prevalence vs. males. Our results showed that young and aged HCM mice displayed echocardiographic characteristics of the heart disease condition, yet only aged HCM females displayed anxiety- and depression-like behaviors. Electrocardiographic parameters of sympathetic nervous system activation were increased in aged HCM females vs. controls and correlated with mood disorder-related symptoms. In addition, when compared with controls, aged HCM females exhibited adrenal gland hypertrophy, reduced volume in mood-related brain regions, and reduced hippocampal signaling proteins, such as brain-derived neurotrophic factor and its downstream targets vs. controls. In conclusion, prolonged systemic HCM stress can lead to development of mood disorders, possibly through inducing structural and functional brain changes, and thus, mood disorders in patients with heart disease should not be considered solely a psychologic or situational condition.-Dossat, A. M., Sanchez-Gonzalez, M. A., Koutnik, A. P., Leitner, S., Ruiz, E. L., Griffin, B., Rosenberg, J. T., Grant, S. C., Fincham, F. D., Pinto, J. R. Kabbaj, M. Pathogenesis of depression- and anxiety-like behavior in an animal model of hypertrophic cardiomyopathy. © FASEB.

  6. 5, 8, 11, 14-eicosatetraynoic acid suppresses CCL2/MCP-1 expression in IFN-γ-stimulated astrocytes by increasing MAPK phosphatase-1 mRNA stability

    Directory of Open Access Journals (Sweden)

    Lee Jee

    2012-02-01

    Full Text Available Abstract Background The peroxisome proliferator-activated receptor (PPAR-α activator, 5,8,11,14-eicosatetraynoic acid (ETYA, is an arachidonic acid analog. It is reported to inhibit up-regulation of pro-inflammatory genes; however, its underlying mechanism of action is largely unknown. In the present study, we focused on the inhibitory action of ETYA on the expression of the chemokine, CCL2/MCP-1, which plays a key role in the initiation and progression of inflammation. Methods To determine the effect of ETYA, primary cultured rat astrocytes and microglia were stimulated with IFN-γ in the presence of ETYA and then, expression of CCL2/MCP-1 and MAPK phosphatase (MKP-1 were determined using RT-PCR and ELISA. MKP-1 mRNA stability was evaluated by treating actinomycin D. The effect of MKP-1 and human antigen R (HuR was analyzed by using specific siRNA transfection system. The localization of HuR was analyzed by immunocytochemistry and subcellular fractionation experiment. Results We found that ETYA suppressed CCL2/MCP-1 transcription and secretion of CCL2/MCP-1 protein through up-regulation of MKP-1mRNA levels, resulting in suppression of c-Jun N-terminal kinase (JNK phosphorylation and activator protein 1 (AP1 activity in IFN-γ-stimulated brain glial cells. Moreover, these effects of ETYA were independent of PPAR-α. Experiments using actinomycin D revealed that the ETYA-induced increase in MKP-1 mRNA levels reflected an increase in transcript stability. Knockdown experiments using small interfering RNA demonstrated that this increase in MKP-1 mRNA stability depended on HuR, an RNA-binding protein known to promote enhanced mRNA stability. Furthermore, ETYA-induced, HuR-mediated mRNA stabilization resulted from HuR-MKP-1 nucleocytoplasmic translocation, which served to protect MKP-1 mRNA from the mRNA degradation machinery. Conclusion ETYA induces MKP-1 through HuR at the post-transcriptional level in a receptor-independent manner. The mechanism

  7. Imaging hypertrophic heart diseases with cardiovascular MR

    Energy Technology Data Exchange (ETDEWEB)

    Proctor, Robin D.; Shambrook, James S.; McParland, Paula; Peebles, Charles R.; Brown, Ivan W. [Department of Cardiothoracic Radiology, Southampton University Hospitals NHS Trust, Southampton (United Kingdom); Harden, Stephen P., E-mail: stephen.harden@suht.swest.nhs.u [Department of Cardiothoracic Radiology, Southampton University Hospitals NHS Trust, Southampton (United Kingdom)

    2011-02-15

    The assessment of ventricular hypertrophy is an increasingly common indication for cardiac MR (CMR) in every day clinical practice. CMR is useful to confirm the presence of hypertrophy and to help to define the underlying cause through a combination of a detailed assessment of ventricular function and tissue characterising sequences. As well as being a useful diagnostic tool, some CMR imaging features are of prognostic significance. In this article, we review the typical appearances of common forms of ventricular hypertrophy, focussing principally on left ventricular hypertrophy, and demonstrate the techniques that can be used to differentiate one form of hypertrophy from another.

  8. Interplay between the E2F pathway and β-adrenergic signaling in the pathological hypertrophic response of myocardium.

    Science.gov (United States)

    Major, Jennifer L; Salih, Maysoon; Tuana, Balwant S

    2015-07-01

    The E2F/Pocket protein (Rb) pathway regulates cell growth, differentiation, and death by modulating gene expression. We previously examined this pathway in the myocardium via manipulation of the unique E2F repressor, E2F6, which is believed to repress gene activity independently of Rb. Mice with targeted expression of E2F6 in postnatal myocardium developed dilated cardiomyopathy (DCM) without hypertrophic growth. We assessed the mechanisms of the apparent failure of compensatory hypertrophic growth as well as their response to the β-adrenergic agonist isoproterenol. As early as 2 weeks, E2F6 transgenic (Tg) mice present with dilated thinner left ventricles and significantly reduced ejection fraction and fractional shortening which persists at 6 weeks of age, but with no apparent increase in left ventricle weight: body weight (LVW:BW). E2F6-Tg mice treated with isoproterenol (6.1 mg/kg/day) show double the increase in LVW:BW than their Wt counterparts (32% vs 16%, p-value: 0.007). Western blot analysis revealed the activation of the adrenergic pathway in Tg heart tissue under basal conditions with ~2-fold increase in the level of β2-adrenergic receptors (p-value: 8.9E-05), protein kinase A catalytic subunit (PKA-C) (p-value: 0.0176), activated c-Src tyrosine-protein kinase (p-value: 0.0002), extracellular receptor kinase 2 (ERK2) (p-value: 0.0005), and induction of the anti-apoptotic protein Bcl2 (p-value 0. 0.00001). In contrast, a ~60% decrease in the cardiac growth regulator: AKT1 (p-value 0.0001) and a ~four fold increase in cyclic AMP dependent phosphodiesterase 4D (PDE4D), the negative regulator of PKA activity, were evident in the myocardium of E2F6-Tg mice. The expression of E2F3 was down-regulated by E2F6, but was restored by isoproterenol. Further, Rb expression was down-regulated in Tg mice in response to isoproterenol implying a net activation of the E2F pathway. Thus the unique regulation of E2F activity by E2F6 renders the myocardium hypersensitive

  9. Co action of CFTR and AQP1 increases permeability of peritoneal epithelial cells on estrogen-induced ovarian hyper stimulation syndrome

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    Jin Pei-Yin

    2012-08-01

    Full Text Available Abstract Background Ovarian hyper stimulation syndrome (OHSS is an iatrogenic complication associated with fertility drugs. It is characterized by increased vascular permeability and substantial fluid shift with accumulation in the body cavity. The pathogenesis of OHSS remains obscure, and no definitive treatments are currently available. Results Using western blot and short-circuit current (Isc techniques, we investigate the potential coactions of analysis in cystic fibrosis transmembrane conductance regulator (CFTR and aquaporin 1 (AQP1 on the hyper permeability of body cavity peritoneal epithelial cells in the pathogenesis of OHSS. The rats develop OHSS symptoms, with the up regulation of both CFTR and AQP1 expression and enhanced CFTR channel activity in peritoneal epithelial cells, can also be mimicked by administration of estrogen, alone in ovariectomized rats. Administration of progesterone suppresses CFTR activity, OHSS symptoms as well as CFTR and AQP1 expression. Besides, AQP1 inhibitor, HgCl2, can suppress CFTR channel activity. Therefore, antisera against CFTR or AQP1 to OHSS animals may result in alleviation of the symptom. Conclusion This study confirms the coactions of CFTR and AQP1 play a critical role in the development and progression of increased peritoneal epithelial permeability in severe OHSS. These findings may provide grounds for ameliorating assisted reproduction treatment strategy to reduce the risk of OHSS in in vitro fertilization (IVF.

  10. A C-terminal fragment of Agouti-related protein increases feeding and antagonizes the effect of alpha-melanocyte stimulating hormone in vivo.

    Science.gov (United States)

    Rossi, M; Kim, M S; Morgan, D G; Small, C J; Edwards, C M; Sunter, D; Abusnana, S; Goldstone, A P; Russell, S H; Stanley, S A; Smith, D M; Yagaloff, K; Ghatei, M A; Bloom, S R

    1998-10-01

    Agouti-related protein (Agrp) is present in rat and human hypothalamus and is structurally related to agouti protein. Overexpression of either of these proteins results in obesity. However the effect of exogenous Agrp and its in vivo interaction with alpha-melanocyte stimulating hormone (alphaMSH), the likely endogenous melanocortin 3 and 4 receptor (MC3-R and MC4-R) agonist, have not been demonstrated. We report that 1 nmol of Agrp(83-132), a C-terminal fragment of Agrp, when administered intracerebroventricularly (ICV) into rats, increased food intake over a 24-h period (23.0+/-1.4 g saline vs 32.9+/-2.3 g Agrp, pinhibition of cAMP activation to that previously reported for the full length peptide. In conclusion, Agrp(83-132) administered i.c.v. increases feeding with long lasting effects and is able to inhibit the action of alphaMSH. This interaction may be mediated by the MC3-R and/or MC4-R.

  11. Propolis Reduces Phosphatidylcholine-Specific Phospholipase C Activity and Increases Annexin a7 Level in Oxidized-LDL-Stimulated Human Umbilical Vein Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Hongzhuan Xuan

    2014-01-01

    Full Text Available To understand the mechanisms underlying the regulating dyslipidemia action of Chinese propolis and Brazilian green propolis, we investigated their effects on phosphatidylcholine-specific phospholipase C (PC-PLC activity and annexin a7 (ANXA7 level which play crucial roles in the control of the progress of atherosclerosis. Furthermore, active oxygen species (ROS levels, nuclear factor-KappaB p65 (NF-κB p65, and mitochondrial membrane potential (MMP were also investigated in oxidized-LDL- (ox-LDL- stimulated human umbilical vein endothelial cells (HUVECs. Our data indicated that the treatment of both types of propolis 12.5 μg/mL significantly increased cell viability and attenuated apoptosis rate, increased ANXA7 level, and decreased PC-PLC activity. Both types of propolis also inhibited ROS generation as well as the subsequent MMP collapse, and NF-κB p65 activation induced by ox-LDL in HUVECs. Our results also indicated that Chinese propolis and Brazilian green propolis had similar biological activities and prevented ox-LDL induced cellular dysfunction in HUVECs.

  12. DHEA prevents mineralo- and glucocorticoid receptor-induced chronotropic and hypertrophic actions in isolated rat cardiomyocytes.

    Science.gov (United States)

    Mannic, Tiphaine; Mouffok, Mounira; Python, Magaly; Yoshida, Takehisa; Maturana, Andres D; Vuilleumier, Nicolas; Rossier, Michel F

    2013-03-01

    Corticosteroids have been involved in the genesis of ventricular arrhythmias associated with pathological heart hypertrophy, although molecular mechanisms responsible for these effects have not been completely explained. Because mineralocorticoid receptor (MR) antagonists have been demonstrated to be beneficial on the cardiac function, much attention has been given to the action of aldosterone on the heart. However, we have previously shown that both aldosterone and corticosterone in vitro induce a marked acceleration of the spontaneous contractions, as well as a significant cell hypertrophy in isolated neonate rat ventricular cardiomyocytes. Moreover, a beneficial role of the steroid hormone dehydroepiandrosterone (DHEA) has been also proposed, but the mechanism of its putative cardioprotective function is not known. We found that DHEA reduces both the chronotropic and the hypertrophic responses of cardiomyocytes upon stimulation of MR and glucocorticoid receptor (GR) in vitro. DHEA inhibitory effects were accompanied by a decrease of T-type calcium channel expression and activity, as assessed by quantitative PCR and the patch-clamp technique. Prevention of cell hypertrophy by DHEA was also revealed by measuring the expression of A-type natriuretic peptide and BNP. The kinetics of the negative chronotropic effect of DHEA, and its sensitivity to actinomycin D, pointed out the presence of both genomic and nongenomic mechanisms of action. Although the genomic action of DHEA was effective mostly upon MR activation, its rapid, nongenomic response appeared related to DHEA antioxidant properties. On the whole, these results suggest new mechanisms for a putative cardioprotective role of DHEA in corticosteroid-associated heart diseases.

  13. Keloids and Hypertrophic Scar/span>s: Update and Future Directions

    Science.gov (United States)

    Huang, Chenyu; Murphy, George F.; Akaishi, Satoshi

    2013-01-01

    Summary: The development of cutaneous pathological scar/span>s, namely, hypertrophic scar/span>s (HSs) and keloids, involves complex pathways, and the exact mechanisms by which they are initiated, evolved, and regulated remain to be fully elucidated. The generally held concepts that keloids and HSs represent “aberrant wound healing” or that they are “characterized by hyalinized collagen bundles” have done little to promote their accurate clinicopathological classification or to stimulate research into the specific causes of these scars and effective preventative therapies. To overcome this barrier, we review here the most recent findings regarding the pathology and pathogenesis of keloids and HSs. The aberrations of HSs and keloids in terms of the inflammation, proliferation, and remodeling phases of the wound healing process are described. In particular, the significant roles that the extracellular matrix and the epidermal and dermal layers of skin play in scar pathogenesis are examined. Finally, the current hypotheses of pathological scar etiology that should be tested by basic and clinical investigators are detailed. Therapies that have been found to be effective are described, including several that evolved directly from the aforementioned etiology hypotheses. A better understanding of pathological scar etiology and manifestations will improve the clinical and histopathological classification and treatment of these important lesions. PMID:25289219

  14. The Huntington's disease-related cardiomyopathy prevents a hypertrophic response in the R6/2 mouse model.

    Directory of Open Access Journals (Sweden)

    Michal Mielcarek

    Full Text Available Huntington's disease (HD is neurodegenerative disorder for which the mutation results in an extra-long tract of glutamines that causes the huntingtin protein to aggregate. It is characterized by neurological symptoms and brain pathology that is associated with nuclear and cytoplasmic aggregates and with transcriptional deregulation. Despite the fact that HD has been recognized principally as a neurological disease, there are multiple epidemiological studies showing that HD patients exhibit a high rate of cardiovascular events leading to heart failure. To unravel the mechanistic basis of cardiac dysfunction in HD, we employed a wide range of molecular techniques using the well-established genetic R6/2 mouse model that develop a considerable degree of the cardiac atrophy at end stage disease. We found that chronic treatment with isoproterenol, a potent beta-adrenoreceptor agonist, did not change the overall gross morphology of the HD murine hearts. However, there was a partial response to the beta-adrenergenic stimulation by the further re-expression of foetal genes. In addition we have profiled the expression level of Hdacs in the R6/2 murine hearts and found that the isoproterenol stimulation of Hdac expression was partially blocked. For the first time we established the Hdac transcriptional profile under hypertrophic conditions and found 10 out of 18 Hdacs to be markedly deregulated. Therefore, we conclude that R6/2 murine hearts are not able to respond to the chronic isoproterenol treatment to the same degree as wild type hearts and some of the hypertrophic signals are likely attenuated in the symptomatic HD animals.

  15. Subaortic and midventricular obstructive hypertrophic cardiomyopathy with extreme segmental hypertrophy

    Directory of Open Access Journals (Sweden)

    Karoulas Takis

    2007-03-01

    Full Text Available Abstract Background Subaortic and midventricular hypertrophic cardiomyopathy in a patient with extreme segmental hypertrophy exceeding the usual maximum wall thickness reported in the literature is a rare phenomenon. Case Presentation A 19-year-old man with recently diagnosed hypertrophic cardiomyopathy (HCM was referred for sudden death risk assessment. The patient had mild exertional dyspnea (New York Heart Association functional class II, but without syncope or chest pain. There was no family history of HCM or sudden death. A two dimensional echocardiogram revealed an asymmetric type of LV hypertrophy; anterior ventricular septum = 49 mm; posterior ventricular septum = 20 mm; anterolateral free wall = 12 mm; and posterior free wall = 6 mm. The patient had 2 types of obstruction; a LV outflow obstruction due to systolic anterior motion of both mitral leaflets (Doppler-estimated 38 mm Hg gradient at rest; and a midventricular obstruction (Doppler-estimated 43 mm Hg gradient, but without apical aneurysm or dyskinesia. The patient had a normal blood pressure response on exercise test and no episodes of non-sustained ventricular tachycardia in 24-h ECG recording. Cardiac MRI showed a gross late enhancement at the hypertrophied septum. Based on the extreme degree of LV hypertrophy and the myocardial hyperenhancement, an implantation of a cardioverter-defibrillator was recommended prophylactically for primary prevention of sudden death. Conclusion Midventricular HCM is an infrequent phenotype, but may be associated with an apical aneurysm and progression to systolic dysfunction (end-stage HCM.

  16. Family communication in a population at risk for hypertrophic cardiomyopathy.

    Science.gov (United States)

    Batte, Brittany; Sheldon, Jane P; Arscott, Patricia; Huismann, Darcy J; Salberg, Lisa; Day, Sharlene M; Yashar, Beverly M

    2015-04-01

    Encouraging family communication is an integral component of genetic counseling; therefore, we sought to identify factors impacting communication to family members at risk for Hypertrophic Cardiomyopathy (HCM). Participants (N = 383) completed an online survey assessing: 1) demographics (gender, genetic test results, HCM family history, and disease severity); 2) illness representations; 3) family functioning and cohesiveness; 4) coping styles; 5) comprehension of HCM autosomal dominant inheritance; and 6) communication of HCM risk information to at-risk relatives. Participants were a national sample of individuals with HCM, recruited through the Hypertrophic Cardiomyopathy Association. Data from 183 participants were analyzed using a logistic regression analysis, with family communication as a dichotomous dependent variable. We found that female gender and higher comprehension of autosomal dominant inheritance were significant predictors of participants' communication of HCM risk information to all their siblings and children. Our results suggest that utilizing interventions that promote patient comprehension (e.g., a teaching-focused model of genetic counseling) are important and may positively impact family communication within families with HCM.

  17. CT findings of intrathoricic neoplasm associated with hypertrophic osteoarthropathy

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    Hwang, Hee Sung; Choe, Kyu Ok; Chung, Jin Il; Oh, Sei Chung [College of Medicine Yonsei University, Seoul (Korea, Republic of)

    1994-02-15

    Hypertrophic osteoarthropathy(HOA) is a clinical syndrome consisting of clubbing, periostitis and synovitis. Most frequent causes of hypertrophic osteoarthropathy are intrathoracic neoplasms, among which the bronchogenic carcinoma ranks the highest. But computed tomographic evaluation of intrathoracic neoplasm associated with HOA has been seldom reported. The purpose of this study is to evaluate CT findings of intrathoracic neoplasm associated with HOA, and to infer possible mechanism. Seven cases of intrathoracic neoplasm associated with HOA were included in our study. Diagnoses of HOA were made by Tc99m bone scintigraphy or plain radiography. The findings of chest CT scans were reviewed retrospectively, with main interests on their size, location and internal characteristics, ect. Seven cases of intrathoracic neoplasm consisted of five bronchogenic carcinomas and two thymic tumors. The size of intrathoracic tumors were relatively large ranging from 6cm to 13cm(average 8.0cm). All thoracic neoplasms showed wide pleural contact, and one of them invaded thoracic wall. The range of length of pleural contact was 5-18cm(average 9.9cm). All of seven patients had internal necrosis, and one of them showed cavitation in thoracic mass. Intrathoracic neoplasms associated with HOA had a tendency to be large, to contain internal necrosis, and to widely abut the thoracic pleura.

  18. Planktonic ciliates in a hypertrophic pond: functional role and importance.

    Science.gov (United States)

    Sanchez Rodriguez, Ma del Rosario; Lugo Vazquez, Alfonso; Oliva Martinez, Ma Guadalupe; Verver y Vargas, Jaqueline Garcia; Rodriguez Rocha, Armando; Peralta Soriano, Laura

    2011-07-01

    Taxonomical composition and abundance of the planktonic ciliate assemblage in a Lake Tezozomoc, a hypertrophic pond located into an urban park in Mexico City, was investigated along the rainy season (May to October). The aims of the study were to know the main trophic roles and ecological significance of ciliates in a highly productive environment. A low number of taxa (27) and a wide abundance fluctuation (104-387 cil ml(-1)) were found. The most abundant species (up to 162 cil ml(-1)) was Halteria grandinella, an oligotrich ciliate that graze on bacteria and picoplankton, but also several big body sized species that feed on pico and nanoplankton were abundant. Sudden temporal changes in species dominance occurred. Ciliate biomass was very high and fluctuated widely (1.6-88 10(6) microm(3) ml(-1)) being dominated by the >50 microm size fraction that mainly included the pico and nanoplankton feeders. Ciliates are a very important component in the plankton of hypertrophic lakes and their main control factor seems to be the grazing by big-body size Daphnia species.

  19. Sucrose and naltrexone prevent increased pain sensitivity and impaired long-term memory induced by repetitive neonatal noxious stimulation: Role of BDNF and β-endorphin.

    Science.gov (United States)

    Nuseir, Khawla Q; Alzoubi, Karem H; Alhusban, Ahmed; Bawaane, Areej; Al-Azzani, Mohammed; Khabour, Omar F

    2017-10-01

    Pain in neonates is associated with short and long-term adverse outcomes. Data demonstrated that long-term consequences of untreated pain are linked to the plasticity of the neonate's brain. Sucrose is effective and safe for reducing painful procedures from single events. However, the mechanism of sucrose-induced analgesia is not fully understood. The role of the opioid system in this analgesia using the opioid receptor antagonist Naltrexone was investigated, plus the long-term effects on learning and memory formation during adulthood. Pain was induced in rat pups via needle pricks of the paws. Sucrose solution and/or naltrexone were administered before the pricks. All treatments started on day one of birth and continued for two weeks. At the end of 8weeks, behavioral studies were conducted to test spatial learning and memory using radial arm water maze (RAWM), and pain threshold via foot-withdrawal response to a hot plate. The hippocampus was dissected; levels of brain derived neurotrophic factor (BDNF) and endorphins were assessed using ELISA. Acute repetitive neonatal pain increased pain sensitivity later in life, while naltrexone with sucrose decreased pain sensitivity. Naltrexone and/or sucrose prevented neonatal pain induced impairment of long-term memory, while neonatal pain decreased levels of BDNF in the hippocampus; this decrease was averted by sucrose and naltrexone. Sucrose with naltrexone significantly increased β-endorphin levels in noxiously stimulated rats. In conclusion, naltrexone and sucrose can reverse increased pain sensitivity and impaired long-term memory induced by acute repetitive neonatal pain probably by normalizing BDNF expression and increasing β-endorphin levels. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Hypertrophic Cardiomyopathy: New Evidence Since the 2011 American Cardiology of Cardiology Foundation and American Heart Association Guideline.

    Science.gov (United States)

    Fraiche, Ariane; Wang, Andrew

    2016-07-01

    Since publication of the 2011 American College of Cardiology Foundation (ACCF) and American Heart Association (AHA) Guideline for the diagnosis and treatment of hypertrophic cardiomyopathy (HCM), more recent studies offer greater insights about this condition. With increased recognition of the role of sarcomere protein mutations and myocardial structural abnormalities in the pathophysiology of this disease, new evidence offers potential improvements for the management of patients with HCM. In this review of studies published since 2011, we highlight several studies that may impact diagnostic considerations, risk stratification, and treatment of symptoms in HCM.

  1. Concomitant Caffeine Increases Binge Consumption of Ethanol in Adolescent and Adult Mice, But Produces Additive Motor Stimulation Only in Adolescent Animals.

    Science.gov (United States)

    Fritz, Brandon M; Quoilin, Caroline; Kasten, Chelsea R; Smoker, Michael; Boehm, Stephen L

    2016-06-01

    Binge co-consumption of highly caffeinated energy drinks with alcohol (ethanol [EtOH]) has become a common practice among adolescents/young adults and has been associated with an increased incidence of hazardous behaviors. Animal models are critical in advancing our understanding the neurobehavioral consequences of this form of binge drinking. Surprisingly, virtually no work has explored caffeine and EtOH co-consumption or its long-term consequences in adolescent animals. The primary objective of the current study was to extend a previously established mouse model of voluntary binge caffeine and EtOH co-consumption to explore adolescent consumption and responses compared to adults. Adolescent and adult male C57BL/6J mice had daily limited access to caffeine (0.03% w/v), EtOH (20% v/v), a combined EtOH/caffeine solution, or water for 14 days via the binge-like drinking paradigm, drinking-in-the-dark (DID). Home cage locomotor activity was measured during DID in a subset of mice. Following DID, all mice rested for 18 days so that adolescents reached adulthood, whereupon all mice underwent 7 days of continuous access 2-bottle choice drinking for 10% (v/v) EtOH or water. Co-consumption with caffeine significantly increased EtOH intake and resultant blood ethanol concentrations in both adolescent and adult mice. In addition, adolescent mice exhibited a uniquely robust locomotor stimulant response to caffeine and EtOH co-consumption. Later EtOH intake and preference was not influenced, however, by prior fluid consumption history via DID. Together with findings from the human literature, our results suggest that caffeine co-consumption may positively influence binge alcohol consumption in adolescents/young adults. Importantly, this age group may be particularly sensitive to the additive stimulant effects of caffeinated alcohol consumption, an effect which may be related to the high incidence of associated negative outcomes in this population. These observations are

  2. Effects of losartan on left ventricular hypertrophy and fibrosis in patients with nonobstructive hypertrophic cardiomyopathy.

    Science.gov (United States)

    Shimada, Yuichi J; Passeri, Jonathan J; Baggish, Aaron L; O'Callaghan, Caitlin; Lowry, Patricia A; Yannekis, Gia; Abbara, Suhny; Ghoshhajra, Brian B; Rothman, Richard D; Ho, Carolyn Y; Januzzi, James L; Seidman, Christine E; Fifer, Michael A

    2013-12-01

    The aim of this study was to evaluate the effects of losartan on left ventricular (LV) hypertrophy and fibrosis in patients with nonobstructive hypertrophic cardiomyopathy (HCM). Despite evidence that myocardial hypertrophy and fibrosis are mediated by angiotensin II and are important determinants of morbidity and mortality in patients with HCM, no prior studies have evaluated the effects of angiotensin receptor blockers on LV hypertrophy and fibrosis with cardiac magnetic resonance imaging. In double-blind fashion, 20 patients (3 women, 17 men; age: 51 ± 13 years) with HCM were randomly assigned to receive placebo (n = 9) or losartan 50 mg twice a day (n = 11) for 1 year. Cardiac magnetic resonance imaging was performed at baseline and 1 year to measure LV mass and extent of fibrosis as assessed by late gadolinium enhancement. There was a trend toward a significant difference in the percent change in LV mass (median [interquartile range]: +5% [-4% to +21%] with placebo vs. -5% [-11% to -0.9%] with losartan; p = 0.06). There was a significant difference in the percent change in extent of late gadolinium enhancement, with the placebo group experiencing a larger increase (+31% ± 26% with placebo vs. -23% ± 45% with losartan; p = 0.03). This pilot study suggests attenuation of progression of myocardial hypertrophy and fibrosis with losartan in patients with nonobstructive HCM. Confirmation of these results in a larger trial is required to confirm a place for angiotensin receptor blockers in the management of patients with HCM. (Effect of Losartan in Patients With Nonobstructive Hypertrophic Cardiomyopathy; NCT01150461). Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  3. Rising CO2 Levels Will Intensify Phytoplankton Blooms in Eutrophic and Hypertrophic Lakes

    Science.gov (United States)

    Verspagen, Jolanda M. H.; Van de Waal, Dedmer B.; Finke, Jan F.; Visser, Petra M.; Van Donk, Ellen; Huisman, Jef

    2014-01-01

    Harmful algal blooms threaten the water quality of many eutrophic and hypertrophic lakes and cause severe ecological and economic damage worldwide. Dense blooms often deplete the dissolved CO2 concentration and raise pH. Yet, quantitative prediction of the feedbacks between phytoplankton growth, CO2 drawdown and the inorganic carbon chemistry of aquatic ecosystems has received surprisingly little attention. Here, we develop a mathematical model to predict dynamic changes in dissolved inorganic carbon (DIC), pH and alkalinity during phytoplankton bloom development. We tested the model in chemostat experiments with the freshwater cyanobacterium Microcystis aeruginosa at different CO2 levels. The experiments showed that dense blooms sequestered large amounts of atmospheric CO2, not only by their own biomass production but also by inducing a high pH and alkalinity that enhanced the capacity for DIC storage in the system. We used the model to explore how phytoplankton blooms of eutrophic waters will respond to rising CO2 levels. The model predicts that (1) dense phytoplankton blooms in low- and moderately alkaline waters can deplete the dissolved CO2 concentration to limiting levels and raise the pH over a relatively wide range of atmospheric CO2 conditions, (2) rising atmospheric CO2 levels will enhance phytoplankton blooms in low- and moderately alkaline waters with high nutrient loads, and (3) above some threshold, rising atmospheric CO2 will alleviate phytoplankton blooms from carbon limitation, resulting in less intense CO2 depletion and a lesser increase in pH. Sensitivity analysis indicated that the model predictions were qualitatively robust. Quantitatively, the predictions were sensitive to variation in lake depth, DIC input and CO2 gas transfer across the air-water interface, but relatively robust to variation in the carbon uptake mechanisms of phytoplankton. In total, these findings warn that rising CO2 levels may result in a marked intensification of

  4. ENerGetIcs in hypertrophic cardiomyopathy: traNslation between MRI, PET and cardiac myofilament function (ENGINE study).

    Science.gov (United States)

    Güçlü, A; Germans, T; Witjas-Paalberends, E R; Stienen, G J M; Brouwer, W P; Harms, H J; Marcus, J T; Vonk, A B A; Stooker, W; Yilmaz, A; Klein, P; Ten Berg, J M; Kluin, J; Asselbergs, F W; Lammertsma, A A; Knaapen, P; van Rossum, A C; van der Velden, J

    2013-12-01

    Hypertrophic cardiomyopathy (HCM) is an autosomal dominant heart disease mostly due to mutations in genes encoding sarcomeric proteins. HCM is characterised by asymmetric hypertrophy of the left ventricle (LV) in the absence of another cardiac or systemic disease. At present it lacks specific treatment to prevent or reverse cardiac dysfunction and hypertrophy in mutation carriers and HCM patients. Previous studies have indicated that sarcomere mutations increase energetic costs of cardiac contraction and cause myocardial dysfunction and hypertrophy. By using a translational approach, we aim to determine to what extent disturbances of myocardial energy metabolism underlie disease progression in HCM. Hypertrophic obstructive cardiomyopathy (HOCM) patients and aortic valve stenosis (AVS) patients will undergo a positron emission tomography (PET) with acetate and cardiovascular magnetic resonance imaging (CMR) with tissue tagging before and 4 months after myectomy surgery or aortic valve replacement + septal biopsy. Myectomy tissue or septal biopsy will be used to determine efficiency of sarcomere contraction in-vitro, and results will be compared with in-vivo cardiac performance. Healthy subjects and non-hypertrophic HCM mutation carriers will serve as a control group. Our study will reveal whether perturbations in cardiac energetics deteriorate during disease progression in HCM and whether these changes are attributed to cardiac remodelling or the presence of a sarcomere mutation per se. In-vitro studies in hypertrophied cardiac muscle from HOCM and AVS patients will establish whether sarcomere mutations increase ATP consumption of sarcomeres in human myocardium. Our follow-up imaging study in HOCM and AVS patients will reveal whether impaired cardiac energetics are restored by cardiac surgery.

  5. Risk factors for sudden cardiac death in childhood hypertrophic cardiomyopathy: A systematic review and meta-analysis.

    Science.gov (United States)

    Norrish, Gabrielle; Cantarutti, Nicoletta; Pissaridou, Eleni; Ridout, Deborah A; Limongelli, Giuseppe; Elliott, Perry M; Kaski, Juan Pablo

    2017-07-01

    Aims To perform a systematic literature review and meta-analysis of clinical risk factors for sudden cardiac death (SCD) in childhood hypertrophic cardiomyopathy. Methods Medline and PubMed databases were searched for original articles published in English from 1963 through to December 2015 that included patients under 18 years of age with a primary or secondary end-point of either SCD or SCD-equivalent events (aborted cardiac arrest or appropriate implantable cardioverter-defibrillator discharge) or cardiovascular death (CVD). Results Twenty-five studies (3394 patients) met the inclusion criteria. We identified four conventional major risk factors that were evaluated in at least four studies and that we found to be statistically associated with an increased risk of death in at least two studies: previous adverse cardiac event (pooled hazard ratio [HR] 5.4, 95% confidence interval [CI] 3.67-7.95, p cardiomyopathy means that the evidence base for individual risk factors is not robust. We have identified four clinical parameters that are likely to be associated with increased risk of SCD, SCD-equivalent events or CVD. Multi-centre prospective studies are needed in order to further determine the relevance of these factors in predicting SCD in childhood hypertrophic cardiomyopathy and to identify novel risk markers. Condensed abstract A systematic review and meta-analysis of clinical risk factors predicting sudden cardiac death in childhood hypertrophic cardiomyopathy was performed, identifying four 'major' factors: previous adverse cardiac event; non-sustained ventricular tachycardia; syncope; and extreme left ventricular hypertrophy. Well-designed multi-centre studies are required in the future in order to confirm these findings.

  6. Nicotine stimulates pancreatic cancer xenografts by systemic increase in stress neurotransmitters and suppression of the inhibitory neurotransmitter gamma-aminobutyric acid.

    Science.gov (United States)

    Al-Wadei, Hussein A N; Plummer, Howard K; Schuller, Hildegard M

    2009-03-01

    Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer mortality in Western countries. We have shown previously that four representative human PDAC cell lines were regulated by beta-adrenoreceptors via cyclic adenosine 3',5'-monophosphate (cAMP)-dependent signaling. In the current study, we have tested the hypothesis that nicotine stimulates the growth of PDAC xenografts in nude mice by increasing the systemic levels of the stress neurotransmitters adrenaline and noradrenaline, which are the physiological agonists for beta-adrenoreceptors and that inhibition by gamma-aminobutyric acid (GABA) of the adenylyl cyclase-dependent pathway downstream of adrenoreceptors blocks this effect. The size of xenografts from PDAC cell line Panc-1 was determined 30 days after inoculation of the cancer cells. Stress neurotransmitters in serum as well as cAMP in the cellular fraction of blood and in tumor tissue were assessed by immunoassays. Levels of GABA, its synthesizing enzymes GAD65 and GAD67 and beta-adrenergic signaling proteins in the tumor tissue were determined by western blotting. Nicotine significantly increased the systemic levels of adrenaline, noradrenaline and cAMP while increasing xenograft size and protein levels of cAMP, cyclic AMP response element-binding protein and p-extracellular signal-regulated kinase 1/2 in the tumor tissue. Nicotine additionally reduced the protein levels of both GAD isozymes and GABA in tumor tissue. Treatment with GABA abolished these responses to nicotine and blocked the development of xenografts in mice not exposed to nicotine. These findings suggest that the development and progression of PDAC is subject to significant modulation by stimulatory stress neurotransmitters and inhibitory GABA and that treatment with GABA may be useful for marker-guided cancer intervention of PDAC.

  7. Changes in gadolinium-DTPA enhanced magnetic resonance signal intensity ratio in hypertrophic cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Tsukihashi, Hironori; Ishibashi, Yutaka; Shimada, Toshio; Hatano, Jun; Tanabe, Kazuaki; Ooyake, Nobuyuki; Morioka, Shigefumi; Moriyama, Katsutoshi (Shimane Medical Univ., Izumo (Japan))

    Serial gadolinium-diethylene-triamine-pentaacetic acid (Gd-DTPA) enhanced magnetic resonance (MR) signal intensity ratios were measured in 6 normal subjects and 20 hypertrophic cardiomyopathy (HCM) patients to try to differentiate normal from disorganized myocardial tissue. Images were obtained at 10-minute intervals 5-60 minutes after Gd-DTPA (0.1 mmol/kg) injection. The signal intensity ratio (myocardial signal intensity/skeletal muscle signal intensity) was measured at both hypertrophic and non-hypertrophic regions in each image at the apex and mid-ventricular levels. The signal intensity ratio was standardized to compare each case. Hypertrophic myocardium was classified into two types. Type I in 11 of 20 patients was visualized as a homogeneous image, while type II in the other 9 patients was revealed as a mixed isointensity and high intensity area. The peak value of the standardized signal intensity ratio at the apex level was 1.28[+-]0.09 in HCM patients and 1.23[+-]0.06 in normal subjects, and at the mid ventricular level was 1.26[+-]0.07 in hypertrophic regions, 1.17[+-]0.12 in non-hypertrophic regions, and 1.16[+-]0.07 in normal subjects. Thirty minutes after Gd injection, the standardized signal intensity ratio at the apex level was 1.21[+-]0.08 in HCM patients and 1.07[+-]0.08 in normal subjects, and those at the mid ventricular level was 1.20[+-]0.09 in hypertrophic regions, 1.11[+-]0.11 in non-hypertrophic regions, and 1.04[+-]0.06 in normal subjects. The delayed decay of the signal intensity ratio and high signal intensity ratio in Gd-DTPA enhanced MR images are useful in myocardial tissue characterization in hypertrophic cardiomyopathy. (author).

  8. Whey proteins have beneficial effects on intestinal enteroendocrine cells stimulating cell growth and increasing the production and secretion of incretin hormones.

    Science.gov (United States)

    Gillespie, Anna L; Calderwood, Danielle; Hobson, Laura; Green, Brian D

    2015-12-15

    Whey protein has been indicated to curb diet-induced obesity, glucose intolerance and delay the onset of type 2 diabetes mellitus. Here the effects of intact crude whey, intact individual whey proteins and beta-lactoglobulin hydrolysates on an enteroendocrine (EE) cell model were examined. STC-1 pGIP/neo cells were incubated with several concentrations of yogurt whey (YW), cheese whey (CW), beta-lactoglobulin (BLG), alpha-lactalbumin (ALA) and bovine serum albumin (BSA). The findings demonstrate that BLG stimulates EE cell proliferation, and also GLP-1 secretion (an effect which is lost following hydrolysis with chymotrypsin or trypsin). ALA is a highly potent GLP-1 secretagogue which also increases the intracellular levels of GLP-1. Conversely, whey proteins and hydrolysates had little impact on GIP secretion. This appears to be the first investigation of the effects of the three major proteins of YW and CW on EE cells. The anti-diabetic potential of whey proteins should be further investigated. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Increasing muscle strength and mass of thigh in elderly people with the hybrid-training method of electrical stimulation and volitional contraction.

    Science.gov (United States)

    Takano, Yoshio; Haneda, Yoshihiro; Maeda, Takashi; Sakai, Yutaka; Matsuse, Hiroo; Kawaguchi, Takumi; Tagawa, Yoshihiko; Shiba, Naoto

    2010-05-01

    The "Hybrid training" (HYBT) method utilizing combined electrical stimulation and voluntary muscle contraction has been developed as a muscle training method. It has already been shown that the method is technically sound and clinically effective in healthy young subjects. The purpose of this study was to investigate the effect of the HYBT method on the knee extensor strength considering safety for elderly people. Twenty subjects were randomly divided into two groups: the HYBT group and the weight machine training (WMT) group. All the subjects performed knee flexion and extension for 19 min per session, twice a week for 12 weeks. At the baseline and after the training, the subjects' maximal isometric torque of knee extension and cross-sectional area (CSA) of quadriceps femoris muscle were measured. The subjects completed the study without adverse effects. The knee extension torque significantly increased in both groups (39% in HYBT group and 42% in WMT group, P muscle strength and mass, and that this method is as effective as the WMT. In addition, unlike the WMT, the HYBT device, which is portable and not large in size, is so easy to handle that it can be placed at the bedside. Therefore, the HYBT has potential to become a safe, effective method of muscle training for elderly people.

  10. The increase in the cardiodepressant activity and vasopressin concentration in the sella turcica venous blood during vagal afferents stimulation or after angiotensin II infusion

    Energy Technology Data Exchange (ETDEWEB)

    Goraca, A.; Orlowska-Majdak, M.; Traczyk, W.Z. [Akademia Medyczna, Lodz (Poland). Katedra Fizjologii

    1996-12-31

    It has previously been demonstrated that the cardiodepressant activity is present in the bovine hypothalamic extract and in the fluid incubating the posterior pituitary lobe {sup i}n situ{sup .} The present study was an attempt to reveal if the cardiodepressant factor and vasopressin were simultaneously released from the pituitary into blood. The samples of venous blood flowing from the sella turcica and, for comparison, from the posterior paw were collected in anesthetized rats. Blood from the sella turcica was collected with a fine cannula inserted into the internal maxillary vein. The concentration of vasopressin in blood plasma was determined by radioimmunoassay and cardiodepressant activity-using a biological test on a spontaneously discharged pacemaker tissue of the right auricle of the right heart atrium. Stimulation of the central ends of the cut vagus nerves or intra-arterial infusion of angiotensin II simultaneously caused an increase in the cardiodepressant activity and vasopressin concentration in the sella turcica venous blood. The cardiodepressant activity and vasopressin concentration was also enhanced to some degree in blood outflowing from the posterior paw. Present results indicate that both vasopressin and the cardiodepressant factor are released into blood from the posterior pituitary lobe. (author). 37 refs, 4 figs.

  11. Preclinical Study of Novel Gene Silencer Pyrrole-Imidazole Polyamide Targeting Human TGF-β1 Promoter for Hypertrophic Scar/span>s in a Common Marmoset Primate Model

    Science.gov (United States)

    Igarashi, Jun; Fukuda, Noboru; Inoue, Takashi; Nakai, Shigeki; Saito, Kosuke; Fujiwara, Kyoko; Matsuda, Hiroyuki; Ueno, Takahiro; Matsumoto, Yoshiaki; Watanabe, Takayoshi; Nagase, Hiroki; Bando, Toshikazu; Sugiyama, Hiroshi; Itoh, Toshio; Soma, Masayoshi

    2015-01-01

    We report a preclinical study of a pyrrole-imidazole (PI) polyamide that targets the human transforming growth factor (hTGF)-β1 gene as a novel transcriptional gene silencer in a common marmoset primate model. We designed and then synthesized PI polyamides to target the hTGF-β1 promoter. We examined effects of seven PI polyamides (GB1101-1107) on the expression of hTGF-β1 mRNA stimulated with phorbol 12-myristate 13-acetate (PMA) in human vascular smooth muscle cells. GB1101, GB1105 and GB1106 significantly inhibited hTGF-β1 mRNA expression. We examined GB1101 as a PI polyamide to hTGF-β1 for hypertrophic scar/span>s in marmosets in vivo. Injection of GB1101 completely inhibited hypertrophic scar formation at 35 days post-incision and inhibited cellular infiltration, TGF-β1 and vimentin staining, and epidermal thickness. Mismatch polyamide did not affect hypertrophic scarring or histological changes. Epidermis was significantly thinner with GB1101 than with water and mismatch PI polyamides. We developed the PI polyamides for practical ointment medicines for the treatment of hypertrophic scar/span>s. FITC-labeled GB1101 with solbase most efficiently distributed in the nuclei of epidermal keratinocytes, completely suppressed hypertropic scarring at 42 days after incision, and considerably inhibited epidermal thickness and vimentin-positive fibroblasts. PI polyamides targeting hTGF-β1 promoter with solbase ointment will be practical medicines for treating hypertrophic scar/span>s after surgical operations and skin burns. PMID:25938472

  12. Cardiac sarcoid: a chameleon masquerading as hypertrophic cardiomyopathy and dilated cardiomyopathy in the same patient.

    Science.gov (United States)

    Agarwal, Anushree; Sulemanjee, Nasir Z; Cheema, Omar; Downey, Francis X; Tajik, A Jamil

    2014-05-01

    Sarcoidosis is a multisystem, granulomatous disease of unknown etiology often seen in young adults, with cardiac involvement in more than one-quarter of sarcoid patients. The clinical presentation of cardiac sarcoid depends upon the location and extent of myocardium involved. Although cardiac sarcoid may produce asymmetrical septal hypertrophy, it is most commonly considered in the differential diagnosis of dilated cardiomyopathy. The hypertrophic stage of cardiac sarcoid is rarely seen. We describe a case of cardiac sarcoid in a young patient wherein a distinctive appearance of the cardiac sarcoid spectrum from "hypertrophic" stage to thinned/scarred stage, masquerading as hypertrophic cardiomyopathy followed by dilated cardiomyopathy, is demonstrated. © 2014, Wiley Periodicals, Inc.

  13. Down Syndrome with Complete Atrioventricular Septal Defect, Hypertrophic Cardiomyopathy, and Pulmonary Vein Stenosis.

    Science.gov (United States)

    Mahadevaiah, Guruprasad; Gupta, Manoj; Ashwath, Ravi

    2015-10-01

    The prevalence of congenital heart disease in infants with Down syndrome is 40%, compared with 0.3% in children who have normal chromosomes. Atrioventricular and ventricular septal defects are often associated with chromosomal aberrations, such as in trisomy 21, whereas hypertrophic cardiomyopathy is chiefly thought to be secondary to specific gene mutations. We found only one reported case of congenital hypertrophic cardiomyopathy and atrioventricular septal defect in an infant with Down syndrome. Here, we report atrioventricular septal defect, hypertrophic cardiomyopathy, and pulmonary vein stenosis in a neonate with Down syndrome-an apparently unique combination. In addition, we discuss the relevant medical literature.

  14. Perioperative anesthetic management of patients with hypertrophic cardiomyopathy for noncardiac surgery: A case series

    Directory of Open Access Journals (Sweden)

    Sahoo Rajendra

    2010-01-01

    Full Text Available Hypertrophic cardiomyopathy with or without left ventricular outflow tract obstruction is characterized by asymmetric hypertrophy of the interventricular septum causing intermittent obstruction of the left ventricular outflow tract. Because Hypertrophic cardiomyopathy is the most common genetic cardiovascular disease, it may present to the anesthesiologist more often than anticipated, sometimes in undiagnosed form during routine preoperative visit. Surgery and anesthesia often complicate the perioperative outcome if adequate monitoring and proper care are not taken. Therefore, a complete understanding of the pathophysiology, hemodynamic changes and anesthetic implications is needed for successful perioperative outcome. We hereby describe the perioperative management of three patients with Hypertrophic cardiomyopathy for different surgical procedures.

  15. Pathogenesis of Hypertrophic Cardiomyopathy is Mutation Rather Than Disease Specific: A Comparison of the Cardiac Troponin T E163R and R92Q Mouse Models.

    Science.gov (United States)

    Ferrantini, Cecilia; Coppini, Raffaele; Pioner, Josè Manuel; Gentile, Francesca; Tosi, Benedetta; Mazzoni, Luca; Scellini, Beatrice; Piroddi, Nicoletta; Laurino, Annunziatina; Santini, Lorenzo; Spinelli, Valentina; Sacconi, Leonardo; De Tombe, Pieter; Moore, Rachel; Tardiff, Jil; Mugelli, Alessandro; Olivotto, Iacopo; Cerbai, Elisabetta; Tesi, Chiara; Poggesi, Corrado

    2017-07-22

    In cardiomyocytes from patients with hypertrophic cardiomyopathy, mechanical dysfunction and arrhythmogenicity are caused by mutation-driven changes in myofilament function combined with excitation-contraction (E-C) coupling abnormalities related to adverse remodeling. Whether myofilament or E-C coupling alterations are more relevant in disease development is unknown. Here, we aim to investigate whether the relative roles of myofilament dysfunction and E-C coupling remodeling in determining the hypertrophic cardiomyopathy phenotype are mutation specific. Two hypertrophic cardiomyopathy mouse models carrying the R92Q and the E163R TNNT2 mutations were investigated. Echocardiography showed left ventricular hypertrophy, enhanced contractility, and diastolic dysfunction in both models; however, these phenotypes were more pronounced in the R92Q mice. Both E163R and R92Q trabeculae showed prolonged twitch relaxation and increased occurrence of premature beats. In E163R ventricular myofibrils or skinned trabeculae, relaxation following Ca(2+) removal was prolonged; resting tension and resting ATPase were higher; and isometric ATPase at maximal Ca(2+) activation, the energy cost of tension generation, and myofilament Ca(2+) sensitivity were increased compared with that in wild-type mice. No sarcomeric changes were observed in R92Q versus wild-type mice, except for a large increase in myofilament Ca(2+) sensitivity. In R92Q myocardium, we found a blunted response to inotropic interventions, slower decay of Ca(2+) transients, reduced SERCA function, and increased Ca(2+)/calmodulin kinase II activity. Contrarily, secondary alterations of E-C coupling and signaling were minimal in E163R myocardium. In E163R models, mutation-driven myofilament abnormalities directly cause myocardial dysfunction. In R92Q, diastolic dysfunction and arrhythmogenicity are mediated by profound cardiomyocyte signaling and E-C coupling changes. Similar hypertrophic cardiomyopathy phenotypes can be

  16. The induction of colitis and ileitis in mice is associated with marked increases in intestinal concentrations of stimulants of TLRs 2, 4, and 5.

    Directory of Open Access Journals (Sweden)

    Clett Erridge

    Full Text Available BACKGROUND: Inflammatory bowel diseases (IBDs appear to be modulated by the interaction of pathogen-associated molecular patterns (PAMPs derived from intestinal bacteria with their respective innate immune receptors, including Toll-like receptors (TLRs. We aimed to establish if intestinal concentrations of proinflammatory bacterial ligands of TLR2, TLR4, or TLR5 may be altered in murine IBD models, and to characterize which of the major bacterial groups may contribute to each signal. METHODOLOGY/PRINCIPAL FINDINGS: PAMPs specific for TLR2 (lipopeptide equivalents, TLR4 (lipopolysaccharide equivalents, and TLR5 (flagellin equivalents in human and murine fecal and intestinal samples were quantified using HEK-293 cells transfected with respective TLRs and calibrated with defined standard PAMPs. The induction of colitis in mice by dextran-sodium-sulphate treatment significantly increased colonic lipopeptide (fourfold and LPS equivalent (550-fold concentrations, while flagellin equivalent concentrations remained similar. The induction of ileitis by oral infection with Toxoplasma gondii dramatically increased ileal concentrations of lipopeptide (370-fold, LPS (3,300-fold, and flagellin equivalents (38-fold, all P<0.01. Analysis of representative strains of the major bacterial groups of the human intestine revealed that enterobacterial species are likely to be more significant contributors of soluble TLR2 and TLR4 stimulants to the intestinal milieu than Bacteroides species or Gram-positive Firmicutes. CONCLUSIONS/SIGNIFICANCE: We conclude that the induction of colitis or ileitis in mice is associated with significant disease-specific alterations to the PAMP profile of the gut microbiota.

  17. Osthole, a coumadin analog from Cnidium monnieri (L.) Cusson, stimulates corticosterone secretion by increasing steroidogenic enzyme expression in mouse Y1 adrenocortical tumor cells.

    Science.gov (United States)

    Pan, Zhiqiang; Fang, Zhaoqin; Lu, Wenli; Liu, Xiaomei; Zhang, Yuanyuan

    2015-12-04

    Osthole is an O-methylated coumadin, which was isolated and purified from the seeds of Cnidium monnieri (L.) Cusson. Osthole is a commonly used traditional Chinese medicine to treat patients with Kidney-Yang deficiency patients, who exhibit clinical signs similar to those of glucocorticoid withdrawal. However, the mechanism of action of osthole is not fully understood. This study was designed to reveal the effects of osthole on corticosterone production in mouse Y1 cell. Mouse Y1 adrenocortical cells were used to evaluate corticosterone production, which was quantified by enzyme-linked immunosorbent assay (ELISA) kits. Cell viability was tested using the MTT assay, and the mRNA and protein expression of genes encoding steroidogenic enzymes and transcription factors was monitored by quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) and western blotting, respectively. Osthole stimulated corticosterone secretion from mouse Y1 cells in a dose- and time-dependent manner, and osthole enhanced the effect of dibutyryl-cAMP (Bu2cAMP) on corticosterone production. Further, osthole also increased StAR and CYP11B1 mRNA expression in a dose-dependent manner and enhanced the expression of transcription factors such as HSD3B1, FDX1, POR and RXRα as well as immediate early genes such as NR4A1. Moreover, osthole significantly increased SCARB1(SRB1) mRNA and StAR protein expression in the presence or absence of Bu2cAMP; these proteins are an important for the transport of the corticosteroid precursor cholesterol transport into mitochondria. Our results show that the promotion of corticosterone biosynthesis and secretion is a novel effect of osthole, suggesting that this agent can be utilized for the prevention and treatment of Kidney-Yang deficiency syndrome. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. Myosin cross-bridges do not form precise rigor bonds in hypertrophic heart muscle carrying troponin T mutations.

    Science.gov (United States)

    Midde, K; Dumka, V; Pinto, J R; Muthu, P; Marandos, P; Gryczynski, I; Gryczynski, Z; Potter, J D; Borejdo, J

    2011-09-01

    Distribution of orientations of myosin was examined in ex-vivo myofibrils from hearts of transgenic (Tg) mice expressing Familial Hypertrophic Cardiomyopathy (FHC) troponin T (TnT) mutations I79N, F110I and R278C. Humans are heterozygous for sarcomeric FHC mutations and so hypertrophic myocardium contains a mixture of the wild-type (WT) and mutated (MUT) TnT. If mutations are expressed at a low level there may not be a significant change in the global properties of heart muscle. In contrast, measurements from a few molecules avoid averaging inherent in the global measurements. It is thus important to examine the properties of only a few molecules of muscle. To this end, the lever arm of one out of every 60,000 myosin molecules was labeled with a fluorescent dye and a small volume within the A-band (~1 fL) was observed by confocal microscopy. This volume contained on average 5 fluorescent myosin molecules. The lever arm assumes different orientations reflecting different stages of acto-myosin enzymatic cycle. We measured the distribution of these orientations by recording polarization of fluorescent light emitted by myosin-bound fluorophore during rigor and contraction. The distribution of orientations of rigor WT and MUT myofibrils was significantly different. There was a large difference in the width and of skewness and kurtosis of rigor distributions. These findings suggest that the hypertrophic phenotype associated with the TnT mutations can be characterized by a significant increase in disorder of rigor cross-bridges. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Evaluation of the effect of fractional CO2 laser on histopathological picture and TGF-β1 expression in hypertrophic scar.

    Science.gov (United States)

    Makboul, Mohamed; Makboul, Rania; Abdelhafez, Assem Hk; Hassan, Safaa Said; Youssif, Sherif M

    2014-09-01

    Hypertrophic scar is a form of abnormal wound healing process in which tissue repair regulating mechanism is disrupted. Transforming growth factor β1 has a particular importance in the fibrotic scarring response. Treatment of hypertrophic scar included many chemical, physical, and surgical options. Fractional CO2 laser devices have gained acceptance as a way for managing hypertrophic scar. Aims of this study are: (a) to determine the clinical and histopathological effects of fractional CO2 laser on hypertrophic scar, (b) to evaluate the expression pattern of transforming growth factor-β1 (TGF-β1) as an important fibrogenic factor before and 6 months after fractional CO2 laser treatment. Forty patients of hypertrophic scar were selected, each patient was treated by four sessions with 1 month apart with fractional CO2 laser. Vancouver Scar Scale (VSS) was used to assess the patients before and after laser treatment. Skin biopsy was taken from eight cases before and 3 months after four fractional CO2 laser sessions and four normal skin control biopsies. All were assessed by hematoxylin-eosin (H&E), Masson's trichrome, Van Gieson and immunohistochemical (IHC) staining with TGF-β1. The epidermal thickness was assessed before and after treatment by image analyzing system software. There was statistically significant difference in VSS before and after fractional CO2 laser (P > 0.001). The epidermal thickness showed significant increase after laser treatment (P > 0.001), and there was also thinning in stratum corneum and replacement of the irregular collagen bands with organized new collagen fibrils as demonstrated by H&E and the other special stains. The study also showed significant decrease in TGF-β1 expression after laser therapy (P = 0.008). Fractional CO2 laser could be considered as a good way for hypertrophic scar management. It normalizes dermal collagen as imaged by histopathological picture and the change in TGF-β1 expression. © 2014 Wiley

  20. Relationship between fibrosis and lactate dehydrogenase isoenzymes in the experimental hypertrophic heart of rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Revis, N.W.; Cameron, A.J.V.

    1978-06-01

    Cardiac hypertrophy was induced in rabbits by injecting either thyroxine or isoprenaline or by surgically constricting the abdominal aorta. An increase in heart weight was associated with a change in the lactate dehydrogenase isoenzyme pattern and an increase in fibrosis (as measured by hydroxyproline concentrations). Isoprenaline treatment led to a moderate increase in heart weight, a marked decrease in the heart/skeletal muscle subunit ratio of lactate dehydrogenase, and a marked increase in hydroxyproline. Thyroxine treatment led to a small increase in both heart weight and hydroxyproline and a small decrease in the heart/skeletal muscle subunit ratio. Coarctation of the aorta, in contrast, caused a marked increase in heart weight, a moderate decrease in heart/skeletal muscle subunit ratio, and a moderate increase in hydroxyproline. These results suggest that the decrease in the heart/skeletal muscle subunit ratio of lactate dehydrogenase in the experimental hypertrophic heart reflects the extent of myocardial fibrosis, rather than changes within the hypertrophied myocardial cells.

  1. Functional characterization of TRAP1-like protein involved in modulating fibrotic processes mediated by TGF-β/Smad signaling in hypertrophic scar fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Wang, X. [Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200011 (China); Department of Pediatric Surgery, Shanghai Children’s Medical Center, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200127 (China); Chu, J. [Department of Pediatric Surgery, Shanghai Children’s Medical Center, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200127 (China); Wen, C.J.; Fu, S.B.; Qian, Y.L. [Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200011 (China); Wo, Y. [Department of Anatomy, Institutes of Medical Sciences, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025 (China); Wang, C., E-mail: wangchen2369@163.com [Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200011 (China); Wang, D.R., E-mail: wangdanru@126.com [Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200011 (China)

    2015-03-15

    The transforming growth factor-β1 (TGF-β)-mediated signaling pathway is believed to be closely associated with wound healing and scar formation, in which TRAP1-like protein (TLP) plays a role in regulating the balance of Smad2 vs. Smad3 signaling. Our previous study revealed the relation between TLP and collagen synthesis in normal human skin fibroblasts. Here, we present a detailed analysis of the effects of TLP on the process of hypertrophic scar formation and contraction. To explore and verify a contribution of TLP to the pathological mechanism of hypertrophic scar fibroblasts (HSFb), we constructed lentiviral vectors that either overexpressed TLP or encoded small hairpin RNAs (shRNAs) targeting TLP, then we transfected them into HSFb. TLP knockdown in HSFb resulted in reduced levels of cell contraction, type I and type III collagen mRNA transcripts and protein expression, and higher levels of fibronectin (FN) compared to control groups. In addition, knockdown of TLP promoted the phosphorylation of Smad3 but repressed Smad2 and Erk-1/2 phosphorylation in human hypertrophic scar fibroblasts compared to control groups. The reduction of TLP did not interfere with HSF proliferative ability, but exogenous TLP cooperated with TGF-β1 to increase cell viability. Together, our findings demonstrate evidence for a contribution of TLP expression in hypertrophic scar formation and contraction. - Highlights: • TLP acted different roles in the activating of Smad2- and Smad3-dependent signaling. • TLP may induce TGF-β1-mediated collagens expression through Smad signalings and MAPK signaling. • TLP may enhance HSFb contraction by increasing the expression of α-SMA. • Exogenous TLP can cooperate with TGF-β1 to increase cell viability.

  2. Ultrastructural myocardial changes in seven cats with spontaneous hypertrophic cardiomyopathy

    DEFF Research Database (Denmark)

    Christiansen, Liselotte Bruun; Prats Gavalda, Clara; Hyttel, Poul

    2015-01-01

    OBJECTIVES: Hypertrophic cardiomyopathy (HCM) is the most common heart disease in cats and shares clinical and pathological characteristics with human HCM. Little is known about the pathogenic mechanisms underlying development of spontaneous feline HCM. ANIMALS: The study population consisted...... of seven cats diagnosed with HCM and eight age-matched cats with no evidence of cardiac disease. METHODS: Fresh myocardial biopsies taken from the middle of the left ventricular posterior free wall were obtained and examined with transmission electron microscopy. RESULTS: Electron microscopic examination...... showed ultrastructural aberrations of the myocardial cytoarchitecture and of the interstitium in the seven cats with HCM. In the most severely affected cats the myofibrils were disorganized and subsarcolemmal mitochondria were depleted. In control cats, contraction band artifacts were commonly seen...