WorldWideScience

Sample records for spontaneous myometrial contractility

  1. Relaxant effect of a novel calcium-activated potassium channel modulator on human myometrial spontaneous contractility in vitro

    DEFF Research Database (Denmark)

    Rosenbaum, S.T.; Larsen, T.; Joergensen, J.C.

    2012-01-01

    Aim: To investigate the effect of 4,5-dichloro-1,3-diethyl-1,3-dihydro-benzoimidazol-2-one (NS4591), a novel SK/IK channels positive modulator, on human myometrial activity. Methods: Organ bath studies were performed on myometrial preparations obtained from women undergoing elective caesarean....... Simultaneous vehicle controls were performed for all experiments. The effects of drugs were studied on spontaneous contractions. Results: NS4591 exerted an inhibitory effect on myometrial contractions in muscle strips from non-pregnant and pregnant women. The contractility in non-pregnant and pregnant...

  2. In vitro myometrial contractility reflects indication for caesarean section.

    Science.gov (United States)

    Quenby, S; Matthew, A; Zhang, J; Dawood, F; Wray, S

    2011-11-01

    To assess the extent to which in vitro measurements of myometrial contractility reflect the clinical indication for caesarean section. A prospective, observational hypothesis-generating study. Women were recruited from Liverpool Women's NHS Foundation Trust and experiments were performed in the Physiology Department at the University of Liverpool. Myometrial samples were taken from women undergoing a caesarean section during labour (n = 50) or from women having a repeat nonlabouring caesarean section (n = 70). The demographic characteristics of the women and indications for current and previous caesarean sections were recorded. The force, frequency and duration of spontaneous contractions of myometrial strips, and changes in the intracellular calcium concentration of the strips, were measured. Kruskall-Wallis and post hoc tests were used to assess the significance of differences between groups. Samples from women whose caesarean section was for fetal distress/acidosis (scalp pH force than those from women whose caesarean section was for delay in the first stage of labour (P force than did samples from women whose first caesarean section was for delay in the first stage of labour (P = 0.03). These findings suggest that the myometrium contracts with greater force in women who have a caesarean section for fetal distress. © 2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2011 RCOG.

  3. High-Throughput Screening of Myometrial Calcium-Mobilization to Identify Modulators of Uterine Contractility.

    Science.gov (United States)

    Herington, Jennifer L; Swale, Daniel R; Brown, Naoko; Shelton, Elaine L; Choi, Hyehun; Williams, Charles H; Hong, Charles C; Paria, Bibhash C; Denton, Jerod S; Reese, Jeff

    2015-01-01

    The uterine myometrium (UT-myo) is a therapeutic target for preterm labor, labor induction, and postpartum hemorrhage. Stimulation of intracellular Ca2+-release in UT-myo cells by oxytocin is a final pathway controlling myometrial contractions. The goal of this study was to develop a dual-addition assay for high-throughput screening of small molecular compounds, which could regulate Ca2+-mobilization in UT-myo cells, and hence, myometrial contractions. Primary murine UT-myo cells in 384-well plates were loaded with a Ca2+-sensitive fluorescent probe, and then screened for inducers of Ca2+-mobilization and inhibitors of oxytocin-induced Ca2+-mobilization. The assay exhibited robust screening statistics (Z´ = 0.73), DMSO-tolerance, and was validated for high-throughput screening against 2,727 small molecules from the Spectrum, NIH Clinical I and II collections of well-annotated compounds. The screen revealed a hit-rate of 1.80% for agonist and 1.39% for antagonist compounds. Concentration-dependent responses of hit-compounds demonstrated an EC50 less than 10μM for 21 hit-antagonist compounds, compared to only 7 hit-agonist compounds. Subsequent studies focused on hit-antagonist compounds. Based on the percent inhibition and functional annotation analyses, we selected 4 confirmed hit-antagonist compounds (benzbromarone, dipyridamole, fenoterol hydrobromide and nisoldipine) for further analysis. Using an ex vivo isometric contractility assay, each compound significantly inhibited uterine contractility, at different potencies (IC50). Overall, these results demonstrate for the first time that high-throughput small-molecules screening of myometrial Ca2+-mobilization is an ideal primary approach for discovering modulators of uterine contractility.

  4. High-Throughput Screening of Myometrial Calcium-Mobilization to Identify Modulators of Uterine Contractility

    Science.gov (United States)

    Herington, Jennifer L.; Swale, Daniel R.; Brown, Naoko; Shelton, Elaine L.; Choi, Hyehun; Williams, Charles H.; Hong, Charles C.; Paria, Bibhash C.; Denton, Jerod S.; Reese, Jeff

    2015-01-01

    The uterine myometrium (UT-myo) is a therapeutic target for preterm labor, labor induction, and postpartum hemorrhage. Stimulation of intracellular Ca2+-release in UT-myo cells by oxytocin is a final pathway controlling myometrial contractions. The goal of this study was to develop a dual-addition assay for high-throughput screening of small molecular compounds, which could regulate Ca2+-mobilization in UT-myo cells, and hence, myometrial contractions. Primary murine UT-myo cells in 384-well plates were loaded with a Ca2+-sensitive fluorescent probe, and then screened for inducers of Ca2+-mobilization and inhibitors of oxytocin-induced Ca2+-mobilization. The assay exhibited robust screening statistics (Z´ = 0.73), DMSO-tolerance, and was validated for high-throughput screening against 2,727 small molecules from the Spectrum, NIH Clinical I and II collections of well-annotated compounds. The screen revealed a hit-rate of 1.80% for agonist and 1.39% for antagonist compounds. Concentration-dependent responses of hit-compounds demonstrated an EC50 less than 10μM for 21 hit-antagonist compounds, compared to only 7 hit-agonist compounds. Subsequent studies focused on hit-antagonist compounds. Based on the percent inhibition and functional annotation analyses, we selected 4 confirmed hit-antagonist compounds (benzbromarone, dipyridamole, fenoterol hydrobromide and nisoldipine) for further analysis. Using an ex vivo isometric contractility assay, each compound significantly inhibited uterine contractility, at different potencies (IC50). Overall, these results demonstrate for the first time that high-throughput small-molecules screening of myometrial Ca2+-mobilization is an ideal primary approach for discovering modulators of uterine contractility. PMID:26600013

  5. The effects of prostaglandin E1 and prostaglandin E2 on in vitro myometrial contractility and uterine structure.

    Science.gov (United States)

    Chiossi, Giuseppe; Costantine, Maged M; Bytautiene, Egle; Kechichian, Talar; Hankins, Gary D V; Sbrana, Elena; Saade, George R; Longo, Monica

    2012-09-01

    To estimate the effects of prostaglandin E1 (PGE1) and E2 (PGE2) on myometrial contractility and structure in vitro. Myometrial strips from 18 women were incubated with PGE1 (10-5 mol/L), PGE2 (10-5 mol/L), or solvent (CTR) for up to 360 minutes in organ chambers for isometric tension recording. The area under the contraction curve, total collagen content, and percentage of the area covered by connective tissue were calculated at various time periods. PGE1 significantly increased in vitro myometrial contractility up to 90 minutes when compared with PGE2 and CTR (p prostaglandins on the uterus cannot be solely explained by contractility. Treatment with PGE1 significantly increased myometrial contractions and decreased both total collagen content and the area covered by connective tissue. Such findings may explain the higher rates of vaginal delivery, tachysystole, and uterine rupture associated with PGE1 use. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  6. Control of myometrial contractility : an experimental study in the chronically instrumented ewe

    NARCIS (Netherlands)

    J. Ramondt (Jaap)

    1991-01-01

    textabstractThis thesis presents the results of experimental studies to evaluate the functional relationship between estrogen and prostanoid action, formation of gap junctions, and myometrial activity. The following questions were specifically addressed: - are estrogen-induced changes in myometrial

  7. Does preincubation with prostaglandin E1 or prostaglandin E2 enhance oxytocin-induced myometrial contractility in vitro?

    Science.gov (United States)

    Chiossi, Giuseppe; Reed, Luckey C; Costantine, Maged M; Hankins, Gary D V; Saade, George R; Longo, Monica

    2013-09-01

    To determine if preincubation with prostaglandin E1 (PGE1) and E2 (PGE2) enhances oxytocin-induced myometrial contractility in vitro. Myometrial strips from 13 women were incubated with PGE1 (10-5 mol/L or 10-6 mol/L), PGE2 (10-5 mol/L or 10-6 mol/L) or solvent before adding cumulative concentrations of oxytocin (10-10 to 10-6 mol/L). The area under the contraction curve was calculated after addition of each agent. One- and two-way analysis of variance was used for comparison (significance p prostaglandins was detected on oxytocin 10-8 mol/L (10-5 mol/L > 10-6 mol/L; p < 0.05). Contrary to the hypothesis, neither PGE1 nor PGE2 enhanced oxytocin-induced myometrial contractility; in fact, PGE2 decreased contractility. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  8. Magnetically Bioprinted Human Myometrial 3D Cell Rings as A Model for Uterine Contractility.

    Science.gov (United States)

    Souza, Glauco R; Tseng, Hubert; Gage, Jacob A; Mani, Arunmani; Desai, Pujan; Leonard, Fransisca; Liao, Angela; Longo, Monica; Refuerzo, Jerrie S; Godin, Biana

    2017-03-23

    Deregulation in uterine contractility can cause common pathological disorders of the female reproductive system, including preterm labor, infertility, inappropriate implantation, and irregular menstrual cycle. A better understanding of human myometrium contractility is essential to designing and testing interventions for these important clinical problems. Robust studies on the physiology of human uterine contractions require in vitro models, utilizing a human source. Importantly, uterine contractility is a three-dimensionally (3D)-coordinated phenomenon and should be studied in a 3D environment. Here, we propose and assess for the first time a 3D in vitro model for the evaluation of human uterine contractility. Magnetic 3D bioprinting is applied to pattern human myometrium cells into rings, which are then monitored for contractility over time and as a function of various clinically relevant agents. Commercially available and patient-derived myometrium cells were magnetically bioprinted into rings in 384-well formats for throughput uterine contractility analysis. The bioprinted uterine rings from various cell origins and patients show different patterns of contractility and respond differently to clinically relevant uterine contractility inhibitors, indomethacin and nifedipine. We believe that the novel system will serve as a useful tool to evaluate the physiology of human parturition while enabling high-throughput testing of multiple agents and conditions.

  9. In vitro effects of ritodrine, magnesium sulfate and their combination on spontaneous contractions of myometrial strips of pregnant rat uteri.

    Science.gov (United States)

    Hacivelioglu, S; Cirpan, T; Cosan Terek, M; Kanit, L; Kazandi, M; Oztekin, K

    2007-01-01

    To investigate in vitro effects of ritodrine, magnesium sulfate and their combination on spontaneous contractions of myometrial strips obtained from pregnant rat uteri. A total of 13 pregnant Sprague Dawley rats with weights between 180-200 g were used in this study. Three strips from each rat were kept in an organ bath containing 20 ml Krebs-Henseleit solution (pH: 7.4 and 37 degrees C). 10(-8) 10(-6) and 10(-4) M concentrations of ritodrine, magnesium sulfate and the combination was applied over myometrial strips in Groups I (n: 10), II (n: 10) and III (n: 8), respectively. Amplitude and frequency of spontaneous myometrial contractions, which were recorded at the beginning of each experiment, were considered as reference values. Amplitude and frequency changes in spontaneous myometrial contractions were calculated at approximately ten-minute intervals right after the application of drugs as the percentage of difference at the first reference response. Magnesium sulfate application did not lead to any significant difference on the amplitude and frequency of contractions at any of its concentrations. 10 and 10(-4) M concentrations of ritodrine caused a significant decrease in the amplitude of contractions. It was also found that ritodrine significantly decreased the frequency values at all concentrations. A significant decrease in amplitude was observed at 10(-8) and 10(-6) M concentrations in the combination group. No significant decrease in frequency values was found at any concentration in the combination group. The tocolytic effect of ritodrine is superior to that of magnesium sulfate.

  10. Spontaneous oscillations of elastic contractile materials with turnover.

    Science.gov (United States)

    Dierkes, Kai; Sumi, Angughali; Solon, Jérôme; Salbreux, Guillaume

    2014-10-03

    Single and collective cellular oscillations driven by the actomyosin cytoskeleton have been observed in numerous biological systems. Here, we propose that these oscillations can be accounted for by a generic oscillator model of a material turning over and contracting against an elastic element. As an example, we show that during dorsal closure of the Drosophila embryo, experimentally observed changes in actomyosin concentration and oscillatory cell shape changes can, indeed, be captured by the dynamic equations studied here. We also investigate the collective dynamics of an ensemble of such contractile elements and show that the relative contribution of viscous and friction losses yields different regimes of collective oscillations. Taking into account the diffusion of force-producing molecules between contractile elements, our theoretical framework predicts the appearance of traveling waves, resembling the propagation of actomyosin waves observed during morphogenesis.

  11. Spontaneous and α-adrenoceptor-induced contractility in human collecting lymphatic vessels require chloride

    DEFF Research Database (Denmark)

    Mohanakumar, Sheyanth; Majgaard, Jens; Telinius, Niklas

    2018-01-01

    - with the impermeant anion aspartate and inhibition of Cl- transport and channels with the clinical diuretics furosemide and bendroflumethiazide, as well as DIDS and NPPB. The molecular expression of calcium-activated chloride channels was investigated by RT-PCR and proteins localized using immunoreactivity....... Spontaneous and norepinephrine-induced contractility in human lymphatic vessels was highly abrogated after Cl- substitution with aspartate. 100‒300µM DIDS or NPPB inhibited spontaneous contractile behavior. Norepinephrine-stimulated tone was furthermore markedly abrogated by 200µM DIDS. Furosemide lowered...

  12. Identification of a myometrial molecular profile for dystocic labor.

    LENUS (Irish Health Repository)

    Brennan, Donal J

    2011-01-01

    The most common indication for cesarean section (CS) in nulliparous women is dystocia secondary to ineffective myometrial contractility. The aim of this study was to identify a molecular profile in myometrium associated with dystocic labor.

  13. Sustained inhibition of rat myometrial gap junctions and contractions by lindane

    Directory of Open Access Journals (Sweden)

    Grindatti Carmen M

    2003-10-01

    Full Text Available Abstract Background Gap junctions increase in size and abundance coincident with parturition, forming an intercellular communication network that permits the uterus to develop the forceful, coordinated contractions necessary for delivery of the fetus. Lindane, a pesticide used in the human and veterinary treatment of scabies and lice as well as in agricultural applications, inhibits uterine contractions in vitro, inhibits myometrial gap junctions, and has been associated with prolonged gestation length in rats. The aim of the present study was to investigate whether brief exposures to lindane would elicit sustained inhibition of rat uterine contractile activity and myometrial gap junction intercellular communication. Methods To examine effects on uterine contraction, longitudinal uterine strips isolated from late gestation (day 20 rats were exposed to lindane in muscle baths and monitored for changes in spontaneous phasic contractions during and after exposure to lindane. Lucifer yellow dye transfer between myometrial cells in culture was used to monitor gap junction intercellular communication. Results During a 1-h exposure, 10 micro M and 100 micro M lindane decreased peak force and frequency of uterine contraction but 1 micro M lindane did not. After removal of the exposure buffer, contraction force remained significantly depressed in uterine strips exposed to 100 micro M lindane, returning to less than 50% basal levels 5 h after cessation of lindane exposure. In cultured myometrial myocytes, significant sustained inhibition of Lucifer yellow dye transfer was observed 24 h after lindane exposures as brief as 10 min and as low as 0.1 micro M lindane. Conclusion Brief in vitro exposures to lindane have long-term effects on myometrial functions that are necessary for parturition, inhibiting spontaneous phasic contractions in late gestation rat uterus and gap junction intercellular communication in myometrial cell cultures.

  14. Sustained inhibition of rat myometrial gap junctions and contractions by lindane

    Science.gov (United States)

    Loch-Caruso, Rita K; Criswell, Kay A; Grindatti, Carmen M; Brant, Kelly A

    2003-01-01

    Background Gap junctions increase in size and abundance coincident with parturition, forming an intercellular communication network that permits the uterus to develop the forceful, coordinated contractions necessary for delivery of the fetus. Lindane, a pesticide used in the human and veterinary treatment of scabies and lice as well as in agricultural applications, inhibits uterine contractions in vitro, inhibits myometrial gap junctions, and has been associated with prolonged gestation length in rats. The aim of the present study was to investigate whether brief exposures to lindane would elicit sustained inhibition of rat uterine contractile activity and myometrial gap junction intercellular communication. Methods To examine effects on uterine contraction, longitudinal uterine strips isolated from late gestation (day 20) rats were exposed to lindane in muscle baths and monitored for changes in spontaneous phasic contractions during and after exposure to lindane. Lucifer yellow dye transfer between myometrial cells in culture was used to monitor gap junction intercellular communication. Results During a 1-h exposure, 10 micro M and 100 micro M lindane decreased peak force and frequency of uterine contraction but 1 micro M lindane did not. After removal of the exposure buffer, contraction force remained significantly depressed in uterine strips exposed to 100 micro M lindane, returning to less than 50% basal levels 5 h after cessation of lindane exposure. In cultured myometrial myocytes, significant sustained inhibition of Lucifer yellow dye transfer was observed 24 h after lindane exposures as brief as 10 min and as low as 0.1 micro M lindane. Conclusion Brief in vitro exposures to lindane have long-term effects on myometrial functions that are necessary for parturition, inhibiting spontaneous phasic contractions in late gestation rat uterus and gap junction intercellular communication in myometrial cell cultures. PMID:14567758

  15. Identification of a Myometrial Molecular Profile for Dystocic Labor

    LENUS (Irish Health Repository)

    Brennan, Donal J

    2011-10-16

    Abstract Background The most common indication for cesarean section (CS) in nulliparous women is dystocia secondary to ineffective myometrial contractility. The aim of this study was to identify a molecular profile in myometrium associated with dystocic labor. Methods Myometrial biopsies were obtained from the upper incisional margins of nulliparous women undergoing lower segment CS for dystocia (n = 4) and control women undergoing CS in the second stage who had demonstrated efficient uterine action during the first stage of labor (n = 4). All patients were in spontaneous (non-induced) labor and had received intrapartum oxytocin to accelerate labor. RNA was extracted from biopsies and hybridized to Affymetrix HuGene U133A Plus 2 microarrays. Internal validation was performed using quantitative SYBR Green Real-Time PCR. Results Seventy genes were differentially expressed between the two groups. 58 genes were down-regulated in the dystocia group. Gene ontology analysis revealed 12 of the 58 down-regulated genes were involved in the immune response. These included (ERAP2, (8.67 fold change (FC)) HLA-DQB1 (7.88 FC) CD28 (2.60 FC), LILRA3 (2.87 FC) and TGFBR3 (2.1 FC)) Hierarchical clustering demonstrated a difference in global gene expression patterns between the samples from dystocic and non-dystocic labours. RT-PCR validation was performed on 4 genes ERAP2, CD28, LILRA3 and TGFBR3 Conclusion These findings suggest an underlying molecular basis for dystocia in nulliparous women in spontaneous labor. Differentially expressed genes suggest an important role for the immune response in dystocic labor and may provide important indicators for new diagnostic assays and potential intrapartum therapeutic targets.

  16. Innexin gap junctions in nerve cells coordinate spontaneous contractile behavior in Hydra polyps.

    Science.gov (United States)

    Takaku, Yasuharu; Hwang, Jung Shan; Wolf, Alexander; Böttger, Angelika; Shimizu, Hiroshi; David, Charles N; Gojobori, Takashi

    2014-01-07

    Nerve cells and spontaneous coordinated behavior first appeared near the base of animal evolution in the common ancestor of cnidarians and bilaterians. Experiments on the cnidarian Hydra have demonstrated that nerve cells are essential for this behavior, although nerve cells in Hydra are organized in a diffuse network and do not form ganglia. Here we show that the gap junction protein innexin-2 is expressed in a small group of nerve cells in the lower body column of Hydra and that an anti-innexin-2 antibody binds to gap junctions in the same region. Treatment of live animals with innexin-2 antibody eliminates gap junction staining and reduces spontaneous body column contractions. We conclude that a small subset of nerve cells, connected by gap junctions and capable of synchronous firing, act as a pacemaker to coordinate the contraction of the body column in the absence of ganglia.

  17. Innexin gap junctions in nerve cells coordinate spontaneous contractile behavior in Hydra polyps

    KAUST Repository

    Takaku, Yasuharu

    2014-01-07

    Nerve cells and spontaneous coordinated behavior first appeared near the base of animal evolution in the common ancestor of cnidarians and bilaterians. Experiments on the cnidarian Hydra have demonstrated that nerve cells are essential for this behavior, although nerve cells in Hydra are organized in a diffuse network and do not form ganglia. Here we show that the gap junction protein innexin-2 is expressed in a small group of nerve cells in the lower body column of Hydra and that an anti-innexin-2 antibody binds to gap junctions in the same region. Treatment of live animals with innexin-2 antibody eliminates gap junction staining and reduces spontaneous body column contractions. We conclude that a small subset of nerve cells, connected by gap junctions and capable of synchronous firing, act as a pacemaker to coordinate the contraction of the body column in the absence of ganglia.

  18. Altered contractile responses of arteries from spontaneously hypertensive rat: The role of endogenous mediators and membrane depolarization

    Czech Academy of Sciences Publication Activity Database

    Bencze, Michal; Behuliak, Michal; Vavřínová, Anna; Zicha, Josef

    2016-01-01

    Roč. 166, Dec 1 (2016), s. 46-53 ISSN 0024-3205 R&D Projects: GA ČR(CZ) GAP304/12/0259; GA MZd(CZ) NV15-25396A Institutional support: RVO:67985823 Keywords : femoral artery * SHR * vascular contractility * adrenergic contraction * tyramine * propranolol * neuropeptide Y Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 2.936, year: 2016

  19. Enhanced myometrial autophagy in postpartum uterine involution

    Directory of Open Access Journals (Sweden)

    Keng-Fu Hsu

    2014-09-01

    Conclusion: Autophagy of myocytes may play an important role in uterine involution. These results have implications for our understanding of myometrial functional adaptations during pregnancy and the physiological role of autophagy in the uterine remodeling events in the postpartum period.

  20. Pennogenin tetraglycoside induces rat myometrial contraction and MLC20 phosphorylation via PLC-IP(3 and RhoA/Rho kinase signaling pathways.

    Directory of Open Access Journals (Sweden)

    Limei Wang

    Full Text Available BACKGROUND: Total steroidal saponins extracted from the rhizome of Paris polyphylla Sm. var. yunnanensis (TSSPs have been widely used in China for the treatment of abnormal uterine bleeding. We previously studied the main active constituents of TSSPs and their structure-activity relationships with respect to rat myometrial contractions. Tg (pennogenin tetraglycoside was identified as one of the active ingredients in TSSPs able to induce rat myometrial contractions. However, the mechanisms underlying the pharmacological actions on uterine activity have not been described clearly. METHODS: Here Tg was screened for effects on contractile activity in isolated uterine strips from estrogen-primed rats and on MLC20 phosphorylation and related signaling pathways in cultured rat myometrial cells as determined by Western blot. Intracellular calcium ([Ca(2+](i was monitored under a confocal microscope using Fluo-4 AM-loaded myometrial cells. RESULTS: Tg dose-dependently stimulated rat myometrial contractions as well as MLC20 phosphorylation in vitro, which could be completely suppressed by an inhibitor of myosin light chain kinase (MLCK. Use of Ca(2+ channel blockers and kinase inhibitors demonstrated that Tg-induced myometrial contractions are mediated by activation of the phospholipase C (PLC-inositol triphosphate (IP3 signaling pathway, resulting in increased MLC20 phosphorylation. Furthermore, Y27632, a specific inhibitor of Rho kinase (ROK, notably suppressed Tg-stimulated myometrial contractions and decreased MLC20 phosphorylation. CONCLUSIONS: These data provide evidence that rat myometrial contractility induced by Tg results from enhanced MLC20 phosphorylation, while both PLC-IP3 and RhoA/ROK signaling pathways mediate the process. These mechanisms may be responsible for the therapeutic effects of TSSPs on abnormal uterine bleeding.

  1. Role of the endocannabinoid system in the control of mouse myometrium contractility during the menstrual cycle.

    Science.gov (United States)

    Pagano, Ester; Orlando, Pierangelo; Finizio, Stefania; Rossi, Antonietta; Buono, Lorena; Iannotti, Fabio Arturo; Piscitelli, Fabiana; Izzo, Angelo A; Di Marzo, Vincenzo; Borrelli, Francesca

    2017-01-15

    Cannabis and cannabinoids are known to affect female reproduction. However, the role of the endocannabinoid system in mouse uterine contractility in the dioestrus and oestrus phases has not been previously investigated. The present study aimed at filling this gap. Endocannabinoid (anandamide and 2-arachidonoylglycerol) levels were measured in mouse uterus at dioestrus and oestrus phases by liquid chromatography-mass spectrometry; quantitative reverse transcription-PCR and western blot were used to measured the expression of cannabinoid receptors and enzymes involved in the metabolism of endocannabinoids. Contractility was evaluated in vitro either on the spontaneous contractions or by stimulating the isolated uterus with exogenous spasmogens. The tissue concentrations of anandamide and 2-AG were reduced in the oestrus phase, compared to dioestrus. Uteri obtained in the dioestrus, but not oestrus, phase showed spontaneous phasic prostaglandin-mediated contractions that were reduced by ACEA (CB 1 receptor agonist) and to a lower extent by JWH133 (CB 2 receptor agonist). These inhibitory effects were counteracted by the corresponding selective antagonists. Neither ACEA nor JWH133 did affect the contractions induced by exogenous PGE 2 in the uterus from the oestrus phase. The FAAH inhibitor JNJ1661010 and, to a lower extent, the MAGL inhibitor JZL184 also reduced spontaneous contractions. It is concluded that the endocannabinoid system undergoes to adaptive changes between the oestrus and dioestrus phases. CB 1 and, to a lower extent, CB 2 receptor activation results in selective inhibition of myometrial contractility, without un-specific relaxing effects on the smooth muscle. These results might be of interest for female marijuana smokers as well as for the design of novel tocolytic agents. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. A Study of Myometrial Growth and Development.

    Science.gov (United States)

    Cramer, Stewart F; Oshri, Assaf; Heller, Debra S

    2015-10-01

    To evaluate myometrial growth and development. Thirty-five autopsy uteri, ranging from 10 weeks' gestation to age 18 years, acquired over 3 decades from 2 hospitals, were studied based on specimen availability, photographed for documentation, and reviewed at the end of the study. Most were embedded in toto, with 1 block and 1 slide per case. Some were immunostained for actin, CD10, MIB-1, and/or trichrome stain for collagen and muscle. Myometrial thickness was measured by ocular micrometry when sections were nontangential and analyzed by paired-sample t tests and bivariate linear regression. Two university-affiliated hospitals. From 20 to 34 weeks, lateral wall corpus thickness increased 6-fold, with a 4- to 6-fold perinatal burst of growth (P development. There was a pubertal burst of inframucosal myometaplasia. Myometaplasia accounted for most myometrial growth, especially in the perinatal and pubertal bursts of growth. Pressure effects, related to myometrial tone, appeared to affect myometrial development. True endocervix, with a fibrous wall and mucinous epithelium, appeared late in development. Copyright © 2015 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  3. Misoprostol modulates the gene expression prostaglandin E2 and oxidative stress markers in myometrial cells.

    Science.gov (United States)

    Konopka, Cristine Kolling; Azzolin, Verônica Farina; Cadoná, Francine Carla; Machado, Alencar Kolinski; Dornelles, Eduardo Bortoluzzi; Barbisan, Fernanda; da Cruz, Ivana Beatrice Mânica

    2016-11-01

    Misoprostol, prostaglandin E1 analogue, used for labour induction. However, one-third of patients who have labour induced with prostaglandins do not reach vaginal delivery. The differential expression of prostaglandin receptors in myometrial cells could account for this differential response. Since delivery physiology also involves modulation of oxidative metabolism that can be potentially affected by pharmacological drugs, in the present investigation the role of misoprostol on expression of prostaglandin receptors, and oxidative markers of myometrial cells was evaluated. Samples of myometrial tissues procured from women with spontaneous (SL) and nonspontaneous (NSL) labours were cultured in vitro and exposed to different concentrations of misoprostol. Gene expression was evaluated by qRT-PCR and oxidative biomarkers were evaluated by spectrophotometric and fluorometric analysis. Cells from SL women presented greater responsiveness to misoprostol, since an upregulation of genes related to increased muscle contraction was observed. Otherwise, cells from NSL women had low responsiveness to misoprostol exposure or even a suppressive effect on the expression of these genes. Oxidative biomarkers that previously have been related to labour physiology were affected by misoprostol treatment: lipoperoxidation and protein carbonylation (PC). However, a decrease in lipoperoxidation was observed only in SL cells treated with low concentrations of misoprostol, whereas a decrease of PC occurred in all samples treated with different misoprostol concentrations. The results suggest a pharmacogenetic effect of misoprostol in labour induction involving differential regulation of EP receptor genes, as well as some minor differential modulation of oxidative metabolism in myometrial cells. Copyright © 2016. Published by Elsevier Inc.

  4. Development and validation of primary human myometrial cell culture models to study pregnancy and labour

    Directory of Open Access Journals (Sweden)

    Mosher Andrea A

    2013-01-01

    Full Text Available Abstract Background The development of the in vitro cell culture model has greatly facilitated the ability to study gene expression and regulation within human tissues. Within the human uterus, the upper (fundal segment and the lower segment may provide distinct functions throughout pregnancy and during labour. We have established primary cultured human myometrial cells, isolated from both upper and lower segment regions of the pregnant human uterus, and validated them for the purpose of studying human pregnancy and labour. The specific objectives of this study were to monitor the viability and characterize the expression profile using selected cellular, contractile and pregnancy associated markers in the primary cultured human myometrial cells. Labour has been described as an inflammatory process; therefore, the ability of these cells to respond to an inflammatory stimulus was also investigated. Methods Myometrial cells isolated from paired upper segment (US and lower segment (LS biopsies, obtained from women undergoing Caesarean section deliveries at term prior to the onset of labour, were used to identify expression of; α smooth muscle actin, calponin, caldesmon, connexin 43, cyclo-oxygenase-2 (COX-2, oxytocin receptor, tropomyosin and vimentin, by RT-PCR and/or immunocytochemistry. Interleukin (IL-1β was used to treat cells, subsequently expression of COX-2 mRNA and release of interleukin-8 (CXCL8, were measured. ANOVA followed by Bonferroni’s multiple comparisons test was performed. Results We demonstrate that US and LS human myometrial cells stably express all markers examined to at least passage ten (p10. Connexin 43, COX-2 and vimentin mRNA expression were significantly higher in LS cells compared to US cells. Both cell populations respond to IL-1β, demonstrated by a robust release of CXCL8 and increased expression of COX-2 mRNA from passage one (p1 through to p10. Conclusions Isolated primary myometrial cells maintain expression of

  5. 17 alpha-hydroxyprogesterone caproate vehicle, castor oil, enhances the contractile effect of oxytocin in human myometrium in pregnancy.

    Science.gov (United States)

    O'Sullivan, Michael D; Hehir, Mark P; O'Brien, Yvonne M; Morrison, John J

    2010-05-01

    The possibility exists that the vehicle for 17-alpha-hydroxyprogesterone caproate, castor oil, exerts an effect on human uterine contractility. The aim of this study was to evaluate its effects on contractility of myometrial preparations that were obtained during pregnancy. Myometrial strips were suspended under isometric conditions. Contractility was induced with oxytocin. Strips were incubated in castor oil or physiologic salt solution and suspended for a further oxytocin challenge. Contractile integrals were compared between both groups. Strips that were exposed to castor oil demonstrated increased contractile activity that was elicited by oxytocin (mean contractility value, 165.53%+/-17.03%; n=8; P=.004), compared with control strips (mean contractility value, 72.57%+/-7.48%; n=8; P=.003). There was a significant increase in contractile activity of the castor oil-exposed strips, compared with those that were exposed to physiologic salt solution (n=8; Pcastor oil results in enhanced oxytocin-induced contractility. Copyright (c) 2010 Mosby, Inc. All rights reserved.

  6. DREAM Is Involved in the Genesis of Inflammation-Induced Prolabour Mediators in Human Myometrial and Amnion Cells

    Directory of Open Access Journals (Sweden)

    Priyanka Goradia

    2018-01-01

    Full Text Available Preterm birth is the primary cause of perinatal morbidity and mortality worldwide. Inflammation induces a cascade of events leading to preterm birth by activating nuclear factor-κB (NF-κB. In nongestational tissues, downstream regulatory element antagonist modulator (DREAM regulates NF-κB activity. Our aims were to analyse DREAM expression in myometrium and fetal membranes obtained at term and preterm and to determine the effect of DREAM inhibition on prolabour mediators in primary myometrial and amnion cells. DREAM mRNA expression was significantly higher in fetal membranes obtained after spontaneous labour compared to nonlabour and in amnion from women with histological preterm chorioamnionitis when compared to amnion from women without chorioamnionitis. In primary myometrial and amnion cells, the effect of DREAM silencing by siRNA was a significant decrease in the expression of proinflammatory cytokine IL-6, the chemokines IL-8 and MCP-1, the adhesion molecule ICAM-1, MMP-9 mRNA expression and activity, and NF-κB transcriptional activity when stimulated with the proinflammatory cytokine IL-1β, the bacterial products fsl-1 or flagellin, or the viral dsRNA analogue poly(I:C. These data suggest that, in states of heightened inflammation, DREAM mRNA expression is increased and that, in myometrial and amnion cells, DREAM regulates proinflammatory and prolabour mediators which may be mediated via NF-κB.

  7. Reproducibility of measurement of myometrial invasion in endometrial carcinoma

    NARCIS (Netherlands)

    Putten, L.J.M. van der; Vijver, K. van der; Bartosch, C.; Davidson, B.; Gatius, S.; Matias-Guiu, X.; McCluggage, W.G.; Toledo, G.; Wurff, A.A. van der; Pijnenborg, J.M.A.; Massuger, L.F.A.G.; Bulten, J.

    2017-01-01

    Myometrial invasion (MI) as a percentage (%MI), categorized into <50 or >/=50 %, is an important predictor of prognosis in endometrial carcinoma. Recent studies suggest that tumor-free distance (TFD) to serosa and the absolute depth of invasion (DOI) might be stronger predictors of prognosis.

  8. Successful pregnancy following trans-myometrial embryo transfer ...

    African Journals Online (AJOL)

    ... factor infertility (poor motility). Routine mock embryo transfer indicated severe cervical stenosis which was confirmed at hysteroscopy. She subsequently had trans-myometrial embryo transfer. Blood pregnancy test at 2 weeks was positive and interval transvaginal ultrasound confirmed 2 viable intrauterine foetal poles.

  9. In Vitro Contractile Response of Rabbit Myometrium to BKCa and KATP Potassium Channel Openers

    Directory of Open Access Journals (Sweden)

    Soňa Fraňová

    2009-01-01

    Full Text Available The aim of the study was to evaluate the participation of ligand-sensitive potassium large conductance calcium-activated channels (BKCa and ATP-sensitive potassium channels in uterine smooth muscle reactivity during different stages of the experimentally induced proliferatory and secretory phase in the sexual cycle in ovariectomised rabbits in vitro. The myometrial reactivity to oxytocin (10-6 mol l-1 was investigated by an in vitro method in female rabbits 14 days after ovariectomy treated with 17β-estradiol - 1 mg/kg/day i.m. for 7 days, or with a combination of progesterone 2 mg/kg/day s.c. for 7 days and 17β-estradiol - 0.2 mg/ kg/day (day 3–7. The strips of myometrial smooth muscle were incubated with a specific opener (NS 1619 and an antagonist (TEA of potassium large conductance calcium-activated channel, or with a specific opener (pinacidil and an antagonist (glybenclamide of ATP-sensitive potassium channels before the administration of oxytocin. NS1619 produced more potent inhibition of the oxytocin-induced contraction during the gestagen dominance (experimental secretory phase than the one observed during the oestrogen dominance (experimental proliferatory phase. TEA antagonized the NS1619 induced inhibition of the myometrial contraction. In the matter of KATP potassium channels, after the administration of pinacidil we observed a similar situation in the changes of myometrial contractility. Pinacidil produced more pronounced inhibition of oxytocin-induced contraction during the secretory phase, and its effect was abolished by the selective inhibitor glybenclamide. Our experimental results indicate that both potassium large conductance calcium-activated channels and ATP-sensitive potassium channels significantly participate in the regulation of myometrial oxytocin-induced contractions and the activity of these channels is probably influenced by the levels of oestrogens and gestagens.

  10. Intrauterine Telemetry to Measure Mouse Contractile Pressure In Vivo

    Science.gov (United States)

    Rada, Cara C.; Pierce, Stephanie L.; Grotegut, Chad A.; England, Sarah K.

    2015-01-01

    A complex integration of molecular and electrical signals is needed to transform a quiescent uterus into a contractile organ at the end of pregnancy. Despite the discovery of key regulators of uterine contractility, this process is still not fully understood. Transgenic mice provide an ideal model in which to study parturition. Previously, the only method to study uterine contractility in the mouse was ex vivo isometric tension recordings, which are suboptimal for several reasons. The uterus must be removed from its physiological environment, a limited time course of investigation is possible, and the mice must be sacrificed. The recent development of radiometric telemetry has allowed for longitudinal, real-time measurements of in vivo intrauterine pressure in mice. Here, the implantation of an intrauterine telemeter to measure pressure changes in the mouse uterus from mid-pregnancy until delivery is described. By comparing differences in pressures between wild type and transgenic mice, the physiological impact of a gene of interest can be elucidated. This technique should expedite the development of therapeutics used to treat myometrial disorders during pregnancy, including preterm labor. PMID:25867820

  11. Fractalkine depresses cardiomyocyte contractility.

    Directory of Open Access Journals (Sweden)

    David Taube

    Full Text Available Our laboratory reported that male mice with cardiomyocyte-selective knockout of the prostaglandin E2 EP4 receptor sub-type (EP4 KO exhibit reduced cardiac function. Gene array on left ventricles (LV showed increased fractalkine, a chemokine implicated in heart failure. We therefore hypothesized that fractalkine is regulated by PGE2 and contributes to depressed contractility via alterations in intracellular calcium.Fractalkine was measured in LV of 28-32 week old male EP4 KO and wild type controls (WT by ELISA and the effect of PGE2 on fractalkine secretion was measured in cultured neonatal cardiomyocytes and fibroblasts. The effect of fractalkine on contractility and intracellular calcium was determined in Fura-2 AM-loaded, electrical field-paced cardiomyocytes. Cardiomyocytes (AVM from male C57Bl/6 mice were treated with fractalkine and responses measured under basal conditions and after isoproterenol (Iso stimulation.LV fractalkine was increased in EP4 KO mice but surprisingly, PGE2 regulated fractalkine secretion only in fibroblasts. Fractalkine treatment of AVM decreased both the speed of contraction and relaxation under basal conditions and after Iso stimulation. Despite reducing contractility after Iso stimulation, fractalkine increased the Ca(2+ transient amplitude but decreased phosphorylation of cardiac troponin I, suggesting direct effects on the contractile machinery.Fractalkine depresses myocyte contractility by mechanisms downstream of intracellular calcium.

  12. Inhibition of isolated human myometrium contractility by minoxidil and reversal by glibenclamide.

    Science.gov (United States)

    Prabhakaran, S S; Dhanasekar, K R; Thomas, E; Jose, R; Peedicayil, J; Samuel, P

    2010-03-01

    This study investigated the ability of the antihypertensive drug minoxidil to inhibit potassium chloride (KCl)-induced contractility of the isolated human myometrium. Twelve strips of myometrium obtained from 12 patients who underwent hysterectomy were triggered to contract with 55 mM KCl before and after incubation with 3 concentrations (1, 3 and 10 microM) of minoxidil. The percent inhibition by minoxidil on the extent of contraction, and the area under the contractile curve of KCl-induced contraction of the myometrial strips was determined. Furthermore, the effect of 10 microM glibenclamide on the inhibition generated by 3 microM minoxidil on KCl-induced contractility was studied. It was found that minoxidil produced a concentration-dependent inhibition of KCl-induced contractility of the myometrium and that glibenclamide reversed this inhibitory effect. These results suggest that the inhibitory effect of minoxidil on isolated human myometrium contractility may prove useful in clinical conditions requiring relaxation of the myometrium. 2010 Prous Science, S.A.U. or its licensors. All rights reserved.

  13. Linking myometrial physiology to intrauterine pressure; how tissue-level contractions create uterine contractions of labor.

    Directory of Open Access Journals (Sweden)

    Roger C Young

    2014-10-01

    Full Text Available The mechanisms used to coordinate uterine contractions are not known. We develop a new model based on the proposal that there is a maximum distance to which action potentials can propagate in the uterine wall. This establishes "regions", where one action potential burst can rapidly recruit all the tissue. Regions are recruited into an organ-level contraction via a stretch-initiated contraction mechanism (myometrial myogenic response. Each uterine contraction begins with a regional contraction, which slightly increases intrauterine pressure. Higher pressure raises tension throughout the uterine wall, which initiates contractions of more regions and further increases pressure. The positive feedback synchronizes regional contractions into an organ-level contraction. Cellular automaton (CA simulations are performed with Mathematica. Each "cell" is a region that is assigned an action potential threshold. An anatomy sensitivity factor converts intrauterine pressure to regional tension through the Law of Laplace. A regional contraction occurs when regional tension exceeds regional threshold. Other input variables are: starting and minimum pressure, burst and refractory period durations, enhanced contractile activity during an electrical burst, and reduced activity during the refractory period. Complex patterns of pressure development are seen that mimic the contraction patterns observed in laboring women. Emergent behavior is observed, including global synchronization, multiple pace making regions, and system memory of prior conditions. The complex effects of nifedipine and oxytocin exposure are simulated. The force produced can vary as a nonlinear function of the number of regions. The simulation directly links tissue-level physiology to human labor. The concept of a uterine pacemaker is re-evaluated because pace making activity may occur well before expression of a contraction. We propose a new classification system for biological CAs that parallels

  14. Evaluation of myometrial invasion in patients with endometrial cancer by magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Matsuura, Yusuke; Kashimura, Masamichi; Shinohara, Michioki; Sakamoto, Chikara (University of Occupational and Environmental Health, Kitakyushu (Japan))

    1992-07-01

    Magnetic Resonance Imaging (MRI) has been widely used for the diagnosis of gynecologic disease. We studied the clinical usefulness of MRI in 34 patients with endometrial cancer from July 1988 to August 1991. Pre-operative pelvic MRI was carried out to evaluate the myometrial invasion in these patients. MRI was accurate in predicting the presence or absence of myometrial invasion in 23 of 34 cases (68%), while echo or CT (computed tomography) was accurate in 26% and 8%. In conclusion, MRI is considered to be the most useful examination for the evaluation of myometrial invasion in endometrial cancer. (author).

  15. In vitro contractile effects of agents used in the clinical management of postpartum haemorrhage.

    Science.gov (United States)

    Morrison, John J; Crosby, David A; Crankshaw, Denis J

    2016-10-15

    Uterine atony is a major cause of postpartum haemorrhage and maternal mortality. However, the comparative pharmacology of agents used to treat this condition is poorly understood. This study evaluates, using human pregnant myometrium in vitro, a range of contractile parameters for agents used in the clinical treatment of atonic postpartum haemorrhage. The effects of oxytocin, carbetocin, ergometrine, carboprost, syntometrine and misoprostol were investigated in 146 myometrial strips from 19 donors. The potency and maximal response values were obtained, and compared, using both maximal amplitude and mean contractile force as indices of contraction. Single, EC50 concentrations of the agents were administered and both force and contraction peak parameters were compared during a 15-min exposure. Differences were considered significant when Poxytocin and carbetocin being the most potent. The most important difference between the agents was in their ability to increase the mean contractile force, with oxytocin superior to all agents except syntometrine. In single dose experiments, mean contractile force was the parameter that separated the agents. In this respect, oxytocin was not statistically different from carboprost or syntometrine, but was superior to all other agents. These findings support a clear role for oxytocin as the first line agent for treatment of postpartum haemorrhage and raise doubts about the potential clinical usefulness of misoprostol. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Calix[4]arene C-99 inhibits myosin ATPase activity and changes the organization of contractile filaments of myometrium

    Directory of Open Access Journals (Sweden)

    R. D. Labyntseva,

    2015-12-01

    Full Text Available Calix[4]arenes are cup-like macrocyclic (polyphenolic compounds, they are regarded as promising molecular “platforms” for the design of new physiologically active compounds. We have earlier found that сalix[4]arenе C-99 inhibits the ATPase activity of actomyosin and myosin subfragment-1 of pig uterus іn vitro. The aim of this study was to investigate the interaction of calix[4]arene C-99 with myosin from rat uterine myocytes. It was found that the ATPase activity of myosin prepared from pre-incubated with 100 mM of calix[4]arene C-99 myocytes was almost 50% lower than in control. Additionally, we have revealed the effect of calix[4]arene C-99 on the subcellular distribution of actin and myosin in uterus myocytes by the method of confocal microscopy. This effect can be caused by reorganization of the structure of the contractile smooth muscle cell proteins due to their interaction with calix[4]arene. The obtained results demonstrate the ability of calix[4]arene C-99 to penetrate into the uterus muscle cells and affect not only the myosin ATPase activity, but also the structure of the actin and myosin filaments in the myometrial cells. Demonstrated ability of calix[4]arene C-99 can be used for development of new pharmacological agents for efficient normalization of myometrial contractile hyperfunction.

  17. [Correlation between the myometrial thickness in the second trimester and preterm delivery in a prospective study].

    Science.gov (United States)

    Guo, Yeqing; Long, Xiangdang; Yao, Sui

    2015-02-01

    To investigate the relationship between preterm delivery and anterior myometrial (MA) thickness measured by ultrasound in the second trimester. The general information and pregnancy outcome of singleton pregnant women who had antenatal visit in the Hunan Provincial People's Hospital between Oct 2010 and Sep 2013 were collected prospectively. The MA thickness was measured at 20-27(+6) gestational weeks. The cases were divided into preterm delivery group and term delivery group. (1) A total of 1 031 pregnant women were recruited in this study. 147 pregnant women were in the preterm delivery group (14.26%, 147/1 031) and 884 women were in the term delivery group (85.74% , 884/1 031). The gestation age at delivery of the preterm delivery group was significantly earlier than the term delivery group [(34.57 ± 2.39) vs (39.23 ± 0.92) weeks, P history of preterm delivery, cesarean delivery rate and gestational age at the time of MA measurement between the two groups (P > 0.05). The incidence of premature rupture of membrane (PROM) in the preterm delivery group and in the term delivery group were 49.0% (72/147) and 15.8% (140/884), respectively, with statistically significant difference (P delivery group was (5.49 ± 1.39) mm, while in the preterm delivery group it was (5.60 ± 0.87) mm. There was no statistically significant difference between the two groups(P > 0.05). The mean value of MA thickness in the spontaneous preterm delivery group was(5.15 ± 0.75) mm, and was (5.61 ± 1.38 ) mm in the term delivery group, with statistically significant difference (P delivery group with PROM it was (5.38 ± 1.12) mm. The difference between the two groups were statistically significant (P 0.05). No correlation was found among PROM and MA thickness(r = 0.058, P > 0.05). However, in the preterm delivery group, the mean value of MA in PPROM was significantly thicker than the spontaneous preterm delivery cases (P delivery and PPROM, while the MA thickness should not be considered as

  18. Lipid-soluble fraction of Shakuyaku-kanzo-to inhibits myometrial contraction in pregnant women.

    Science.gov (United States)

    Sumi, Genichiro; Yasuda, Katsuhiko; Tsuji, Shoko; Kanamori, Chiharu; Tsuzuki, Tomoko; Cho, Hisayuu; Nishigaki, Akemi; Okada, Hidetaka; Kanzaki, Hideharu

    2015-05-01

    Shakuyaku-kanzo-to, a Kampo medicine composed equally of shakuyaku and kanzo, is an antispasmodic drug that can inhibit contraction of uterine smooth muscles in pregnant women and rats. We aimed to test the inhibitory effects of water- and lipid-soluble extracts of shakuyaku-kanzo-to, shakuyaku, and kanzo in order to identify the fraction responsible for inhibiting uterine smooth muscle contraction in pregnancy. Myometrial tissues were obtained from pregnant women and rats. The water- and lipid-soluble fractions of shakuyaku-kanzo-to, shakuyaku, and kanzo were obtained using the method of Bligh and Dyer. Lipid-soluble fractions were also partially purified using thin-layer chromatography (TLC) with a chloroform : methanol : water (65:25:4 by volume) solvent system to yield four TLC fractions. The effect of each fraction on oxytocin-induced myometrial contraction was examined in vitro. Lipid-soluble fractions obtained from shakuyaku-kanzo-to and kanzo inhibited myometrial contraction; water-soluble fractions had no effect. Of the four TLC fractions, the inhibitory effect was greatest with TLC fraction 1 (0.75 effect of shakuyaku-kanzo-to on myometrial contraction. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

  19. Cine MRI during spontaneous cramps in women with menstrual pain.

    Science.gov (United States)

    Hellman, Kevin M; Kuhn, Caroline S; Tu, Frank F; Dillane, Katlyn E; Shlobin, Nathan A; Senapati, Sangeeta; Zhou, Xiaojie; Li, Wei; Prasad, Pottumarthi V

    2018-05-01

    The lack of noninvasive methods to study dysmenorrhea has resulted in poor understanding of the mechanisms underlying pain, insufficient diagnostic tests, and limited treatment options. To address this knowledge gap, we have developed a magnetic resonance imaging-based strategy for continuously monitoring the uterus in relationship to participants' spontaneous pain perception. The study objective was to evaluate whether magnetic resonance imaging can detect real-time changes in myometrial activity during cramping episodes in women with dysmenorrhea, with a handheld squeeze bulb for pain reporting. Sixteen women with dysmenorrhea and 10 healthy control women both on and off their menses were evaluated with magnetic resonance imaging while not taking analgesic medication. Continuous magnetic resonance imaging was acquired using half-Fourier acquisition single-shot turbo spin echo sequence along with simultaneous reporting of pain severity with a squeeze bulb. Pearson's coefficient was used to compare results between reviewers. Proportional differences between women with dysmenorrhea and controls on/off menses were evaluated with a Fisher exact test. The temporal relationships between signal changes were evaluated with Monte Carlo simulations. Spontaneous progressive decreases in myometrial signal intensity were more frequently observed in women on their menses than in the absence of pain in the same women off their menses or participants without dysmenorrhea (P < .01). Women without reductions in myometrial signal intensity on their menses either had a history of endometriosis or were not in pain. Observations of myometrial events were consistently reported between 2 raters blinded to menstrual pain or day status (r = 0.97, P < .001). Episodes of cramping occurred either immediately before or 32-70 seconds after myometrial signal change onset (P < .05). Transient decreases in myometrial uterine T2-weighted signal intensity can be reliably measured in women with

  20. Myometrial invasion in endometrial cancer: diagnostic performance of diffusion-weighted MR imaging at 1.5-T

    International Nuclear Information System (INIS)

    Rechichi, Gilda; Sironi, Sandro; Galimberti, Stefania; Valsecchi, Maria Grazia; Signorelli, Mauro; Perego, Patrizia

    2010-01-01

    To determine the diagnostic accuracy of diffusion-weighted (DW) magnetic resonance (MR) imaging in the preoperative assessment of myometrial invasion by endometrial cancer. In this prospective study, 47 patients with histologically confirmed endometrial cancer underwent preoperative MR imaging and total hysterectomy. The MR protocol included spin-echo multishot T2-weighted, dynamic T1-weighted and DW images acquired with b-values of 0 and 500 s/mm 2 . Myometrial tumour spread was classified as superficial (<50%) or deep (≥50% myometrial thickness). Postoperative histopathological findings served as a reference standard. Indices of diagnostic performance were assessed for each sequence. At histopathological examination, superficial myometrial invasion was found in 34 patients and deep myometrial invasion in 13. In the assessment of tumour invasion, sensitivity, specificity, positive and negative predictive values of T2-weighted images were 92.3%, 76.5%, 60.0% and 96.3%, respectively. The corresponding values for dynamic images were 69.2%, 61.8%, 40.9% and 84.0%, and for DW images 84.6%, 70.6%, 52.4% and 92.3%. T2-weighted and DW imaging proved to be the most accurate techniques for tumour spread determination. DW imaging proved to be accurate in assessing myometrial invasion, and it could replace dynamic imaging as an adjunct to routine T2-weighted imaging for preoperative evaluation of endometrial cancer. (orig.)

  1. Stimulation of the cardiopulmonary baroreflex enhances ventricular contractility in awake dogs: a mathematical analysis study.

    Science.gov (United States)

    Sala-Mercado, Javier A; Moslehpour, Mohsen; Hammond, Robert L; Ichinose, Masashi; Chen, Xiaoxiao; Evan, Sell; O'Leary, Donal S; Mukkamala, Ramakrishna

    2014-08-15

    The cardiopulmonary baroreflex responds to an increase in central venous pressure (CVP) by decreasing total peripheral resistance and increasing heart rate (HR) in dogs. However, the direction of ventricular contractility change is not well understood. The aim was to elucidate the cardiopulmonary baroreflex control of ventricular contractility during normal physiological conditions via a mathematical analysis. Spontaneous beat-to-beat fluctuations in maximal ventricular elastance (Emax), which is perhaps the best available index of ventricular contractility, CVP, arterial blood pressure (ABP), and HR were measured from awake dogs at rest before and after β-adrenergic receptor blockade. An autoregressive exogenous input model was employed to jointly identify the three causal transfer functions relating beat-to-beat fluctuations in CVP to Emax (CVP → Emax), which characterizes the cardiopulmonary baroreflex control of ventricular contractility, ABP to Emax, which characterizes the arterial baroreflex control of ventricular contractility, and HR to Emax, which characterizes the force-frequency relation. The CVP → Emax transfer function showed a static gain of 0.037 ± 0.010 ml(-1) (different from zero; P baroreflex. Following β-adrenergic receptor blockade, the CVP → Emax transfer function showed a static gain of 0.0007 ± 0.0113 ml(-1) (different from control; P baroreflex increases ventricular contractility through β-adrenergic receptor system mediation. Copyright © 2014 the American Physiological Society.

  2. The role of voltage-gated potassium channels in the regulation of mouse uterine contractility

    Directory of Open Access Journals (Sweden)

    Abel Peter W

    2007-11-01

    Full Text Available Abstract Background Uterine smooth muscle cells exhibit ionic currents that appear to be important in the control of uterine contractility, but how these currents might produce the changes in contractile activity seen in pregnant myometrium has not been established. There are conflicting reports concerning the role of voltage-gated potassium (Kv channels and large-conductance, calcium-activated potassium (BK channels in the regulation of uterine contractility. In this study we provide molecular and functional evidence for a role for Kv channels in the regulation of spontaneous contractile activity in mouse myometrium, and also demonstrate a change in Kv channel regulation of contractility in pregnant mouse myometrium. Methods Functional assays which evaluated the effects of channel blockers and various contractile agonists were accomplished by quantifying contractility of isolated uterine smooth muscle obtained from nonpregnant mice as well as mice at various stages of pregnancy. Expression of Kv channel proteins in isolated uterine smooth muscle was evaluated by Western blots. Results The Kv channel blocker 4-aminopyridine (4-AP caused contractions in nonpregnant mouse myometrium (EC50 = 54 micromolar, maximal effect at 300 micromolar but this effect disappeared in pregnant mice; similarly, the Kv4.2/Kv4.3 blocker phrixotoxin-2 caused contractions in nonpregnant, but not pregnant, myometrium. Contractile responses to 4-AP were not dependent upon nerves, as neither tetrodotoxin nor storage of tissues at room temperature significantly altered these responses, nor were responses dependent upon the presence of the endometrium. Spontaneous contractions and contractions in response to 4-AP did not appear to be mediated by BK, as the BK channel-selective blockers iberiotoxin, verruculogen, or tetraethylammonium failed to affect either spontaneous contractions or 4-AP-elicited responses. A number of different Kv channel alpha subunit proteins were

  3. Inhibition of Uterine Contractility by Thalidomide Analogs via Phosphodiesterase-4 Inhibition and Calcium Entry Blockade

    Directory of Open Access Journals (Sweden)

    Eduardo Fernández-Martínez

    2016-10-01

    Full Text Available Uterine relaxation is crucial during preterm labor. Phosphodiesterase-4 (PDE-4 inhibitors have been proposed as tocolytics. Some thalidomide analogs are PDE-4 inhibitors. The aim of this study was to assess the uterus-relaxant properties of two thalidomide analogs, methyl 3-(4-nitrophthalimido-3-(3,4-dimethoxyphenyl-propanoate (4NO2PDPMe and methyl 3-(4-aminophthalimido-3-(3,4-dimethoxyphenyl-propanoate (4APDPMe and were compared to rolipram in functional studies of spontaneous phasic, K+-induced tonic, and Ca2+-induced contractions in isolated pregnant human myometrial tissues. The accumulation of cAMP was quantified in HeLa cells. The presence of PDE-4B2 and phosphorylated myosin light-chain (pMLC, in addition to the effect of thalidomide analogs on oxytocin-induced pMLC, were assessed in human uterine myometrial cells (UtSMCs. Thalidomide analogs had concentration-dependent inhibitory effects on spontaneous and tonic contractions and inhibited Ca2+-induced responses. Tonic contraction was equipotently inhibited by 4APDPMe and rolipram (IC50 = 125 ± 13.72 and 98.45 ± 8.86 µM, respectively. Rolipram and the thalidomide analogs inhibited spontaneous and tonic contractions equieffectively. Both analogs increased cAMP accumulation in a concentration-dependent manner (p < 0.05 and induced changes in the subcellular localization of oxytocin-induced pMLC in UtSMCs. The inhibitory effects of thalidomide analogs on the contractions of pregnant human myometrium tissue may be due to their PDE-4 inhibitory effect and novel mechanism as calcium-channel blockers.

  4. Modulatory effects of taurine on jejunal contractility

    International Nuclear Information System (INIS)

    Yao, Q.Y.; Chen, D.P.; Ye, D.M.; Diao, Y.P.; Lin, Y.

    2014-01-01

    Taurine (2-aminoethanesulfonic acid) is widely distributed in animal tissues and has diverse pharmacological effects. However, the role of taurine in modulating smooth muscle contractility is still controversial. We propose that taurine (5-80 mM) can exert bidirectional modulation on the contractility of isolated rat jejunal segments. Different low and high contractile states were induced in isolated jejunal segments of rats to observe the effects of taurine and the associated mechanisms. Taurine induced stimulatory effects on the contractility of isolated rat jejunal segments at 3 different low contractile states, and inhibitory effects at 3 different high contractile states. Bidirectional modulation was not observed in the presence of verapamil or tetrodotoxin, suggesting that taurine-induced bidirectional modulation is Ca 2+ dependent and requires the presence of the enteric nervous system. The stimulatory effects of taurine on the contractility of isolated jejunal segments was blocked by atropine but not by diphenhydramine or by cimetidine, suggesting that muscarinic-linked activation was involved in the stimulatory effects when isolated jejunal segments were in a low contractile state. The inhibitory effects of taurine on the contractility of isolated jejunal segments were blocked by propranolol and L-NG-nitroarginine but not by phentolamine, suggesting that adrenergic β receptors and a nitric oxide relaxing mechanism were involved when isolated jejunal segments were in high contractile states. No bidirectional effects of taurine on myosin phosphorylation were observed. The contractile states of jejunal segments determine taurine-induced stimulatory or inhibitory effects, which are associated with muscarinic receptors and adrenergic β receptors, and a nitric oxide associated relaxing mechanism

  5. Modulatory effects of taurine on jejunal contractility

    Energy Technology Data Exchange (ETDEWEB)

    Yao, Q.Y.; Chen, D.P.; Ye, D.M.; Diao, Y.P.; Lin, Y. [Dalian Medical University, Dalian, Liaoning (China)

    2014-10-14

    Taurine (2-aminoethanesulfonic acid) is widely distributed in animal tissues and has diverse pharmacological effects. However, the role of taurine in modulating smooth muscle contractility is still controversial. We propose that taurine (5-80 mM) can exert bidirectional modulation on the contractility of isolated rat jejunal segments. Different low and high contractile states were induced in isolated jejunal segments of rats to observe the effects of taurine and the associated mechanisms. Taurine induced stimulatory effects on the contractility of isolated rat jejunal segments at 3 different low contractile states, and inhibitory effects at 3 different high contractile states. Bidirectional modulation was not observed in the presence of verapamil or tetrodotoxin, suggesting that taurine-induced bidirectional modulation is Ca{sup 2+} dependent and requires the presence of the enteric nervous system. The stimulatory effects of taurine on the contractility of isolated jejunal segments was blocked by atropine but not by diphenhydramine or by cimetidine, suggesting that muscarinic-linked activation was involved in the stimulatory effects when isolated jejunal segments were in a low contractile state. The inhibitory effects of taurine on the contractility of isolated jejunal segments were blocked by propranolol and L-NG-nitroarginine but not by phentolamine, suggesting that adrenergic β receptors and a nitric oxide relaxing mechanism were involved when isolated jejunal segments were in high contractile states. No bidirectional effects of taurine on myosin phosphorylation were observed. The contractile states of jejunal segments determine taurine-induced stimulatory or inhibitory effects, which are associated with muscarinic receptors and adrenergic β receptors, and a nitric oxide associated relaxing mechanism.

  6. Modulatory effects of taurine on jejunal contractility

    Directory of Open Access Journals (Sweden)

    Q.Y. Yao

    2014-12-01

    Full Text Available Taurine (2-aminoethanesulfonic acid is widely distributed in animal tissues and has diverse pharmacological effects. However, the role of taurine in modulating smooth muscle contractility is still controversial. We propose that taurine (5-80 mM can exert bidirectional modulation on the contractility of isolated rat jejunal segments. Different low and high contractile states were induced in isolated jejunal segments of rats to observe the effects of taurine and the associated mechanisms. Taurine induced stimulatory effects on the contractility of isolated rat jejunal segments at 3 different low contractile states, and inhibitory effects at 3 different high contractile states. Bidirectional modulation was not observed in the presence of verapamil or tetrodotoxin, suggesting that taurine-induced bidirectional modulation is Ca2+ dependent and requires the presence of the enteric nervous system. The stimulatory effects of taurine on the contractility of isolated jejunal segments was blocked by atropine but not by diphenhydramine or by cimetidine, suggesting that muscarinic-linked activation was involved in the stimulatory effects when isolated jejunal segments were in a low contractile state. The inhibitory effects of taurine on the contractility of isolated jejunal segments were blocked by propranolol and L-NG-nitroarginine but not by phentolamine, suggesting that adrenergic β receptors and a nitric oxide relaxing mechanism were involved when isolated jejunal segments were in high contractile states. No bidirectional effects of taurine on myosin phosphorylation were observed. The contractile states of jejunal segments determine taurine-induced stimulatory or inhibitory effects, which are associated with muscarinic receptors and adrenergic β receptors, and a nitric oxide associated relaxing mechanism.

  7. Modulatory effects of taurine on jejunal contractility

    Science.gov (United States)

    Yao, Q.Y.; Chen, D.P.; Ye, D.M.; Diao, Y.P.; Lin, Y.

    2014-01-01

    Taurine (2-aminoethanesulfonic acid) is widely distributed in animal tissues and has diverse pharmacological effects. However, the role of taurine in modulating smooth muscle contractility is still controversial. We propose that taurine (5-80 mM) can exert bidirectional modulation on the contractility of isolated rat jejunal segments. Different low and high contractile states were induced in isolated jejunal segments of rats to observe the effects of taurine and the associated mechanisms. Taurine induced stimulatory effects on the contractility of isolated rat jejunal segments at 3 different low contractile states, and inhibitory effects at 3 different high contractile states. Bidirectional modulation was not observed in the presence of verapamil or tetrodotoxin, suggesting that taurine-induced bidirectional modulation is Ca2+ dependent and requires the presence of the enteric nervous system. The stimulatory effects of taurine on the contractility of isolated jejunal segments was blocked by atropine but not by diphenhydramine or by cimetidine, suggesting that muscarinic-linked activation was involved in the stimulatory effects when isolated jejunal segments were in a low contractile state. The inhibitory effects of taurine on the contractility of isolated jejunal segments were blocked by propranolol and L-NG-nitroarginine but not by phentolamine, suggesting that adrenergic β receptors and a nitric oxide relaxing mechanism were involved when isolated jejunal segments were in high contractile states. No bidirectional effects of taurine on myosin phosphorylation were observed. The contractile states of jejunal segments determine taurine-induced stimulatory or inhibitory effects, which are associated with muscarinic receptors and adrenergic β receptors, and a nitric oxide associated relaxing mechanism. PMID:25387674

  8. Compensatory Hypertrophy of Skeletal Muscle: Contractile Characteristics

    Science.gov (United States)

    Ianuzzo, C. D.; Chen, V.

    1977-01-01

    Describes an experiment using rats that demonstrates contractile characteristics of normal and hypertrophied muscle. Compensatory hypertrophy of the plantaris muscle is induced by surgical removal of the synergistic gastrocnemium muscle. Includes methods for determination of contractile properties of normal and hypertrophied muscle and…

  9. Cellular contractility requires ubiquitin mediated proteolysis.

    Directory of Open Access Journals (Sweden)

    Yuval Cinnamon

    Full Text Available BACKGROUND: Cellular contractility, essential for cell movement and proliferation, is regulated by microtubules, RhoA and actomyosin. The RhoA dependent kinase ROCK ensures the phosphorylation of the regulatory Myosin II Light Chain (MLC Ser19, thereby activating actomyosin contractions. Microtubules are upstream inhibitors of contractility and their depolymerization or depletion cause cells to contract by activating RhoA. How microtubule dynamics regulates RhoA remains, a major missing link in understanding contractility. PRINCIPAL FINDINGS: We observed that contractility is inhibited by microtubules not only, as previously reported, in adherent cells, but also in non-adhering interphase and mitotic cells. Strikingly we observed that contractility requires ubiquitin mediated proteolysis by a Cullin-RING ubiquitin ligase. Inhibition of proteolysis, ubiquitination and neddylation all led to complete cessation of contractility and considerably reduced MLC Ser19 phosphorylation. CONCLUSIONS: Our results imply that cells express a contractility inhibitor that is degraded by ubiquitin mediated proteolysis, either constitutively or in response to microtubule depolymerization. This degradation seems to depend on a Cullin-RING ubiquitin ligase and is required for cellular contractions.

  10. Role of Stro1+/CD44+ stem cells in myometrial physiology and uterine remodeling during pregnancy.

    Science.gov (United States)

    Mas, Aymara; Prusinski, Lauren; Yang, Qiwei; Diaz-Gimeno, Patricia; Stone, Lelyand; Diamond, Michael P; Simón, Carlos; Al-Hendy, Ayman

    2017-01-01

    Regulation of myometrial functions during pregnancy has been considered the result of the integration of endocrine and mechanical signals. Nevertheless, uterine regeneration is poorly understood, and the cellular source within the gravid uterus is largely unexplored.In this study, we isolated and quantified the myometrial stem cells (MSC) population from pregnant female Eker rat uteri, by using Stro1/CD44 surface markers. We demonstrated that prior parity significantly increased the percentage of Stro1+/CD44+ MSC because of injured tissue response. Interestingly, we established that Stro1+/CD44+ MSC respond efficiently to physiological cues when they were treated in vitro under different dose-dependent pregnant rat serum.Previous studies reveal strong regulatory links between O2 availability and stem cell function. Based on these premises, cell proliferation assays showed that isolated Stro1+/CD44+ MSC possess a higher proliferative rate under hypoxic versus normoxic conditions. We also detected a total of 37 upregulated and 44 downregulated hypoxia-related genes, which were differentially expressed in Stro1+/CD44+ MSC, providing an alternative approach to infer into complex molecular mechanisms such as energy metabolism, inflammatory response, uterine expansion, and/or remodeling.Since these cells preferentially grow under low oxygen conditions, we propose that the increase of the rat uterus during pregnancy involves myometrial oxygen consumption, thereby enhancing MSC proliferation. Moreover, pregnancy-induced mechanical stretching results in hypoxic conditions, ultimately creating an environment that promotes stem cell proliferation and further uterine enlargement, which is essential for a successful pregnancy. In summary, all of these data support that rat Stro1+/CD44+ MSC contribute to uterine enlargement during pregnancy. © The Author 2016. Published by Oxford University Press on behalf of Society for the Study of Reproduction.

  11. Proposed biological linkages between obesity, stress, and inefficient uterine contractility during labor in humans.

    Science.gov (United States)

    Lowe, Nancy K; Corwin, Elizabeth J

    2011-05-01

    Cesarean delivery has reached epidemic proportions in contemporary western healthcare. For otherwise healthy first-time (nulliparous) women at term gestation with a single fetus in a head down position, the most common clinical diagnosis prompting cesarean delivery is dystocia, including clinical terms such as uterine dysfunction, failure to progress, arrest of dilation and/or arrest of descent of the fetal head. In 2006, the cesarean rate for this lowest risk population of childbearing women was 26% in the United States despite the goal of Healthy People 2010 to reduce this rate to 15% from a baseline of 18% in 1998. While multiple lines of evidence suggest that the nulliparous uterus is particularly vulnerable to a diagnosis of uterine dysfunction during labor, pathophysiologic explanations for this dysfunction have not been well described. The acute stress response has been implicated as one factor in this dysfunction for many years, while more recently the growing epidemic of adiposity among women of childbearing age has been suggested as an additional pathway by which myometrial cell function may be disrupted. Using both clinical and in vitro evidence, we hypothesize a combined model in which pathways of acute stress and changes associated with maternal adiposity, particularly exaggerated levels of cholesterol and leptin, may independently and synergistically impair the contractile apparatus of the myocyte leading to the clinical diagnosis of uterine dystocia and subsequent cesarean delivery. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Spontaneous pneumothorax

    Directory of Open Access Journals (Sweden)

    Davari R

    1996-07-01

    Full Text Available A case with bilateral spontaneous pneumothorax was presented. Etiology, mechanism, and treatment were discussed on the review of literature. Spontaneous Pneumothorax is a clinical entity resulting from a sudden non traumatic rupture of the lung. Biach reported in 1880 that 78% of 916 patients with spontaneous pneumothorax had tuberculosis. Kjergaard emphasized 1932 the primary importance of subpleural bleb disease. Currently the clinical spectrum of spontaneous pneumothorax seems to have entered a third era with the recognition of the interstitial lung disease and AIDS as a significant etiology. Standard treatment is including: observation, thoracocentesis, tube thoracostomy. Chemical pleurodesis, bullectomy or wedge resection of lung with pleural abrasion and occasionally pleurectomy. Little information has been reported regarding the efficacy of such treatment in spontaneous pneumothorax secondary to non bleb disease

  13. Basal Plate Myometrial Fibers and Hypertensive Disorders of Pregnancy: A Case-Control Study.

    Science.gov (United States)

    Wang, Ann A; Ernst, Linda M; Miller, Emily S

    2017-01-01

    Introduction Basal plate myometrium (BPMYO), the pathological presence of myometrial fibers in the basal plate, is a common finding on pathological examination of the placenta, yet its clinical correlates are not well studied. As myometrial fibers are frequently located in proximity to poorly converted maternal spiral arteries, our objective was to determine whether BPMYO is associated with hypertensive disorders of pregnancy (HDP), a well-known clinical sequela of abnormal maternal artery remodeling. Methods This case-control study included women who delivered a live-born singleton gestation whose placentas were sent for pathological examination. Cases were women with HDP (gestational hypertension, preeclampsia, or HELLP syndrome) as defined by American College of Obstetricians and Gynecologists. Controls were women without HDP. Women with chronic hypertension were excluded. The primary outcome was the presence of BPMYO. Secondary outcomes included the pathologic stage of BPMYO and the incidence of pathologically defined accreta. Each outcome was compared between cases and controls in bivariable and multivariable analyses. Results Of the 306 women who met inclusion criteria, 230 (75%) had HDP. BPMYO was present in 99 (32%) of placentas. Compared to controls, cases were younger, had higher body mass index, and were more likely to have diabetes, be nulliparous, deliver preterm, and have had a prior cesarean. There were no differences in the incidence of BPMYO, stage of BPMYO, or incidence of pathologically defined accreta between cases and controls. These findings persisted after controlling for potential confounders. Conclusions Although BPMYO may be more common in the setting of abnormal placental vasculature, there is no significant association between BPMYO and HDP.

  14. Cardiac tolerance to ischemia in neonatal spontaneously hypertensive rats

    Czech Academy of Sciences Publication Activity Database

    Charvátová, Z.; Ošťádalová, Ivana; Zicha, Josef; Kuneš, Jaroslav; Maxová, H.; Ošťádal, Bohuslav

    2012-01-01

    Roč. 61, Suppl.1 (2012), S145-S153 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510 Institutional research plan: CEZ:AV0Z50110509 Keywords : neonatal spontaneously hypertensive rats * contractile function * ischemic preconditioning * chronic hypoxia Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.531, year: 2012

  15. Tamsulosin modulates, but does not abolish the spontaneous activity in the guinea pig prostate gland.

    Science.gov (United States)

    Chakrabarty, Basu; Dey, Anupa; Lam, Michelle; Ventura, Sabatino; Exintaris, Betty

    2015-06-01

    To examine the effects of the α1A -adrenoceptor antagonist, tamsulosin, on spontaneous contractile and electrical activity in the guinea-pig prostate gland. The effects of tamsulosin (0.1 and 0.3 nM) were investigated in adult and ageing male guinea pig prostate glands using conventional tension recording and electrophysiological intracellular microelectrode recording techniques. Tamsulosin reduced spontaneous activity, and had different age-dependent effects on adult and ageing guinea pigs at different concentrations. 0.1 nM tamsulosin caused a significantly greater reduction of spontaneous contractile and electrical activity in ageing guinea pigs in comparison to adult guinea pigs. In contrast, 0.3 nM tamsulosin had a significantly greater reduction of spontaneous contractile and electrical activity in adult guinea pigs in comparison to ageing guinea pigs. This study demonstrates that tamsulosin can modulate spontaneous myogenic stromal contractility and the underlying spontaneous electrical activity; tamsulosin does not block spontaneous activity. This reduction in spontaneous activity suggests that downstream cellular mechanisms underlying smooth muscle tone are being targeted, and these may represent novel therapeutic targets to better treat benign prostatic hyperplasia. © 2014 Wiley Periodicals, Inc.

  16. BK channel activation by NS11021 decreases excitability and contractility of urinary bladder smooth muscle

    DEFF Research Database (Denmark)

    Layne, Jeffrey J; Nausch, Bernhard; Olesen, Søren-Peter

    2009-01-01

    reduction was blocked by pretreatment with the BK channel blocker iberiotoxin. NS11021 (3 microM) had no effect on contractions evoked by nerve stimulation. These findings indicate that activating BK channels reduces the force of UBSM spontaneous phasic contractions, principally through decreasing......Large-conductance Ca(2+)-activated potassium (BK) channels play an important role in regulating the function and activity of urinary bladder smooth muscle (UBSM), and the loss of BK channel function has been shown to increase UBSM excitability and contractility. However, it is not known whether...... activation of BK channels has the converse effect of reducing UBSM excitability and contractility. Here, we have sought to investigate this possibility by using the novel BK channel opener NS11021. NS11021 (3 microM) caused an approximately threefold increase in both single BK channel open probability (P...

  17. Actomyosin contractility rotates the cell nucleus

    Science.gov (United States)

    Kumar, Abhishek; Maitra, Ananyo; Sumit, Madhuresh; Ramaswamy, Sriram; Shivashankar, G. V.

    2014-01-01

    The cell nucleus functions amidst active cytoskeletal filaments, but its response to their contractile stresses is largely unexplored. We study the dynamics of the nuclei of single fibroblasts, with cell migration suppressed by plating onto micro-fabricated patterns. We find the nucleus undergoes noisy but coherent rotational motion. We account for this observation through a hydrodynamic approach, treating the nucleus as a highly viscous inclusion residing in a less viscous fluid of orientable filaments endowed with active stresses. Lowering actin contractility selectively by introducing blebbistatin at low concentrations drastically reduced the speed and coherence of the angular motion of the nucleus. Time-lapse imaging of actin revealed a correlated hydrodynamic flow around the nucleus, with profile and magnitude consistent with the results of our theoretical approach. Coherent intracellular flows and consequent nuclear rotation thus appear to be an intrinsic property of cells. PMID:24445418

  18. Levothyroxine treatment generates an abnormal uterine contractility patterns in an in vitro animal model

    Directory of Open Access Journals (Sweden)

    Stéphanie Corriveau, MSc

    2015-12-01

    Conclusion: Our data suggest that changes in myometrial reactivity are induced by T4 treatment. Thus, in conjunction with our previous observations on human myometrial strips, management of hypothyroidism should be improved to reduce the rate of C-sections in this group of patients.

  19. Spontaneous deregulation

    NARCIS (Netherlands)

    Edelman, Benjamin; Geradin, Damien

    Platform businesses such as Airbnb and Uber have risen to success partly by sidestepping laws and regulations that encumber their traditional competitors. Such rule flouting is what the authors call “spontaneous private deregulation,” and it’s happening in a growing number of industries. The authors

  20. Dynamic contrast-enhanced MR imaging to assess physiologic variations of myometrial perfusion

    International Nuclear Information System (INIS)

    Thomassin-Naggara, Isabelle; Balvay, Daniel; Cuenod, Charles A.; Darai, Emile; Marsault, Claude; Bazot, Marc

    2010-01-01

    To prospectively evaluate the ability of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to assess physiological microvascular states in normal myometrium. Eighty-five women (62 women of reproductive age, 23 postmenopausal) undergoing DCE-MRI of the pelvis were included. Microvascular parameters for the inner and outer myometrium were analysed using a pharmacokinetic model. These parameters were tissue blood flow (F), blood volume fraction (V b ), permeability-surface area product (PS), interstitial volume fraction (V e ) and lag time (Dt). In the women of reproductive age, the inner myometrium displayed higher F and PS, lower V b and V e , and longer Dt than the outer myometrium (p = 0.02, p = 0.01, p = 0.005, p = 0.03 and p = 0.01, respectively). The inner myometrium presented microvascular variations during the menstrual cycle with a pre-ovulatory peak followed by a fall reaching a nadir of F and V b about 4 days after ovulation. Compared with women of reproductive age, in the postmenopausal state, F and V b decreased in the outer myometrium, while PS, V e and Dt increased (p < 0.0001, p = 0.001, p = 0.001, p = 0.03 and p = 0.0004, respectively). DCE-MRI is a non-invasive technique that can measure variations of myometrial microcirculation, and thereby be potentially useful to help characterize the role and states of the myometrium in assisted reproductive therapy. (orig.)

  1. Contractile network models for adherent cells.

    Science.gov (United States)

    Guthardt Torres, P; Bischofs, I B; Schwarz, U S

    2012-01-01

    Cells sense the geometry and stiffness of their adhesive environment by active contractility. For strong adhesion to flat substrates, two-dimensional contractile network models can be used to understand how force is distributed throughout the cell. Here we compare the shape and force distribution for different variants of such network models. In contrast to Hookean networks, cable networks reflect the asymmetric response of biopolymers to tension versus compression. For passive networks, contractility is modeled by a reduced resting length of the mechanical links. In actively contracting networks, a constant force couple is introduced into each link in order to model contraction by molecular motors. If combined with fixed adhesion sites, all network models lead to invaginated cell shapes, but only actively contracting cable networks lead to the circular arc morphology typical for strongly adhering cells. In this case, shape and force distribution are determined by local rather than global determinants and thus are suited to endow the cell with a robust sense of its environment. We also discuss nonlinear and adaptive linker mechanics as well as the relation to tissue shape. © 2012 American Physical Society

  2. Elastomeric contractile actuators for hand rehabilitation splints

    Science.gov (United States)

    Carpi, Federico; Mannini, Andrea; De Rossi, Danilo

    2008-03-01

    The significant electromechanical performances typically shown by dielectric elastomer actuators make this polymer technology particularly attractive for possible active orthoses for rehabilitation. Folded contractile actuators made of dielectric elastomers were recently described as a simple configuration, suitable to easily implement linear contractile devices. This paper describes an application of folded actuators for so-called hand splints: they consist of orthotic systems for hand rehabilitation. The dynamic versions of the state-of-the-art splints typically include elastic bands, which exert a passive elastic resistance to voluntary elongations of one or more fingers. In order to provide such splints with the possibility of electrically modulating the compliance of the resistive elements, the substitution of the passive elastic bands with the contractile actuators is here described. The electrical activation of the actuators is used to vary the compliance of the system; this enables modulations of the force that acts as an antagonist to voluntary finger movements, according to programmable rehabilitation exercises. The paper reports results obtained from the first prototype implementations of such a type of system.

  3. Influence of menopausal status on diagnostic accuracy of myometrial invasion in endometrial cancer: diffusion-weighted and dynamic contrast-enhanced MRI at 3 T

    International Nuclear Information System (INIS)

    Lin, G.; Huang, Y.-T.; Chao, A.; Ng, K.-K.; Yang, L.-Y.; Ng, S.-H.; Lai, C.-H.

    2015-01-01

    Aim: To assess the influence of menopausal status on the diagnostic accuracy of diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) for evaluating myometrial invasion in patients diagnosed with endometrial cancer. Materials and methods: In this prospective study, 91 consecutive female patients diagnosed with endometrial cancer were enrolled for preoperative evaluation using 3 T MRI. Two radiologists interpreted myometrial invasion depth on DW (b=1000 s/mm 2 ) and DCE MRI images, with surgical histopathology as the reference standard. Statistical methods included kappa statistics for evaluating reader agreement and diagnostic performance analysis between pre- and postmenopausal groups. Results: Reader agreement of DW MRI was poor (κ=0.20) for premenopausal patients. The diagnostic accuracy of DW MRI in detecting myometrial involvement was significantly lower in premenopausal compared with postmenopausal patients (0.42 versus 0.73, p=0.006). There was no difference in the diagnostic accuracy of DW MRI in detecting deep myometrial invasion between premenopausal and postmenopausal groups (0.94 versus 0.95, p>0.99). Conclusion: For premenopausal patients who plan to receive fertility-preserving treatment for endometrial cancer, DCE MRI is superior to DW MRI in excluding any possible myometrial invasion. For preoperative assessment of deep myometrial invasion, DW MRI can be a legitimate alternative to DCE MRI regardless of menopausal status and is particularly beneficial for patients at risk of nephrogenic systemic fibrosis. - Highlights: • Tumour ADC value is higher in premenopausal patients or with Type 1 cancer. • DWI can be an alternative to DCE for assessing deep myometrial invasion. • Caution should be made in assessing premenopausal patients by using DWI.

  4. The Value of Preoperative CA 125 Levels in Prediction of Myometrial Invasion in Patients with Early-stage Endometrioid- type Endometrial Cancer.

    Science.gov (United States)

    Atguden, Zeynep; Yildiz, Askin; Aksut, Hayri; Yalcin, Serenat Eris; Yalcin, Yakup; Uysal, Dilek; Yetimalar, Hakan

    2016-01-01

    To evaluate the relationship between pre-operative CA-125 levels and myometrial invasion in patients with early-stage endometrioid-type endometrial cancer. Two-hundred and sixty patients were diagnosed with endometrial cancer between January 2007 and December 2012. Of these, 136 patients with stage 1 endometrioid histologic-type and documented pre-operative serum CA-125 levels were included in the study. Age, preoperative CA-125 level, histologic grade, surgical grade, and presence of deep myometrial invasion were recorded. Additionally, 16, 20, and 35 IU/ml cutoff values were used and compared to evaluate the relationship between pre-operative CA-125 levels and myometrial invasion. The average serum CA-125 level was 35.4±36.7 in patients with deep myometrial invasion, and 21.5±35.8 in cases without deep myometrial invasion. The relationship between the presence of deep myometrial invasion and CA-125 cut-off values (16, 20, 35 IU/ml) was statistically significant, although the correlation was weak (pCA-125 cut-off values and the presence of deep myometrial invasion was studied, specifity and sensitivity values were identified as: 0.60-0.68 for 16 IU/ml; 0.73-0.48 for 20 IU/ml; and 0.89-0.33 for 35 IU/ml. The sensitivity of 16 IU/ml cut-off value was higher when compared to other values. This study demonstrates that preoperative serum CA-125 values maybe used as a predictive test in patients with early stage endometrioid-type endometrium cancer, and as a prognostic factor alone. Further studies should be conducted to identify different CA-125 cut-off values in patients with low risk endometrial cancer.

  5. Mechanism of cytokinetic contractile ring constriction in fission yeast.

    Science.gov (United States)

    Stachowiak, Matthew R; Laplante, Caroline; Chin, Harvey F; Guirao, Boris; Karatekin, Erdem; Pollard, Thomas D; O'Shaughnessy, Ben

    2014-06-09

    Cytokinesis involves constriction of a contractile actomyosin ring. The mechanisms generating ring tension and setting the constriction rate remain unknown because the organization of the ring is poorly characterized, its tension was rarely measured, and constriction is coupled to other processes. To isolate ring mechanisms, we studied fission yeast protoplasts, in which constriction occurs without the cell wall. Exploiting the absence of cell wall and actin cortex, we measured ring tension and imaged ring organization, which was dynamic and disordered. Computer simulations based on the amounts and biochemical properties of the key proteins showed that they spontaneously self-organize into a tension-generating bundle. Together with rapid component turnover, the self-organization mechanism continuously reassembles and remodels the constricting ring. Ring constriction depended on cell shape, revealing that the ring operates close to conditions of isometric tension. Thus, the fission yeast ring sets its own tension, but other processes set the constriction rate. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Cell stiffness, contractile stress and the role of extracellular matrix

    International Nuclear Information System (INIS)

    An, Steven S.; Kim, Jina; Ahn, Kwangmi; Trepat, Xavier; Drake, Kenneth J.; Kumar, Sarvesh; Ling, Guoyu; Purington, Carolyn; Rangasamy, Tirumalai; Kensler, Thomas W.; Mitzner, Wayne; Fredberg, Jeffrey J.; Biswal, Shyam

    2009-01-01

    Here we have assessed the effects of extracellular matrix (ECM) composition and rigidity on mechanical properties of the human airway smooth muscle (ASM) cell. Cell stiffness and contractile stress showed appreciable changes from the most relaxed state to the most contracted state: we refer to the maximal range of these changes as the cell contractile scope. The contractile scope was least when the cell was adherent upon collagen V, followed by collagen IV, laminin, and collagen I, and greatest for fibronectin. Regardless of ECM composition, upon adherence to increasingly rigid substrates, the ASM cell positively regulated expression of antioxidant genes in the glutathione pathway and heme oxygenase, and disruption of a redox-sensitive transcription factor, nuclear erythroid 2 p45-related factor (Nrf2), culminated in greater contractile scope. These findings provide biophysical evidence that ECM differentially modulates muscle contractility and, for the first time, demonstrate a link between muscle contractility and Nrf2-directed responses.

  7. Cell stiffness, contractile stress and the role of extracellular matrix

    Energy Technology Data Exchange (ETDEWEB)

    An, Steven S., E-mail: san@jhsph.edu [Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Room E-7616, Baltimore, MD 21205 (United States); Kim, Jina [Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Room E-7616, Baltimore, MD 21205 (United States); Ahn, Kwangmi [Division of Biostatistics, Penn State College of Medicine, Hershey, PA 17033 (United States); Trepat, Xavier [CIBER, Enfermedades Respiratorias, 07110 Bunyola (Spain); Drake, Kenneth J. [Division of Molecular and Integrative Physiological Sciences, Harvard School of Public Health, Boston, MA 02115 (United States); Kumar, Sarvesh; Ling, Guoyu; Purington, Carolyn; Rangasamy, Tirumalai; Kensler, Thomas W.; Mitzner, Wayne [Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Room E-7616, Baltimore, MD 21205 (United States); Fredberg, Jeffrey J. [Division of Molecular and Integrative Physiological Sciences, Harvard School of Public Health, Boston, MA 02115 (United States); Biswal, Shyam [Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Room E-7616, Baltimore, MD 21205 (United States); Division of Pulmonary and Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21205 (United States)

    2009-05-15

    Here we have assessed the effects of extracellular matrix (ECM) composition and rigidity on mechanical properties of the human airway smooth muscle (ASM) cell. Cell stiffness and contractile stress showed appreciable changes from the most relaxed state to the most contracted state: we refer to the maximal range of these changes as the cell contractile scope. The contractile scope was least when the cell was adherent upon collagen V, followed by collagen IV, laminin, and collagen I, and greatest for fibronectin. Regardless of ECM composition, upon adherence to increasingly rigid substrates, the ASM cell positively regulated expression of antioxidant genes in the glutathione pathway and heme oxygenase, and disruption of a redox-sensitive transcription factor, nuclear erythroid 2 p45-related factor (Nrf2), culminated in greater contractile scope. These findings provide biophysical evidence that ECM differentially modulates muscle contractility and, for the first time, demonstrate a link between muscle contractility and Nrf2-directed responses.

  8. Dynamic contrast-enhanced MR imaging to assess physiologic variations of myometrial perfusion

    Energy Technology Data Exchange (ETDEWEB)

    Thomassin-Naggara, Isabelle [Assistance Publique-Hopitaux de Paris, Department of Radiology, Hopital Tenon, Paris (France); Universite Rene Descartes, Laboratoire de Recherche en Imagerie-INSERM U970, Paris (France); Hopital Tenon, Service de Radiologie, Paris (France); Balvay, Daniel [Universite Rene Descartes, Laboratoire de Recherche en Imagerie-INSERM U970, Paris (France); Cuenod, Charles A. [Universite Rene Descartes, Laboratoire de Recherche en Imagerie-INSERM U970, Paris (France); Hopital Europeen Georges Pompidou (HEGP), Department of Radiology, Paris (France); Darai, Emile [Assistance Publique-Hopitaux de Paris, Department of Gynaecology-Obstetrics, Hopital Tenon, Paris (France); Marsault, Claude; Bazot, Marc [Assistance Publique-Hopitaux de Paris, Department of Radiology, Hopital Tenon, Paris (France)

    2010-04-15

    To prospectively evaluate the ability of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to assess physiological microvascular states in normal myometrium. Eighty-five women (62 women of reproductive age, 23 postmenopausal) undergoing DCE-MRI of the pelvis were included. Microvascular parameters for the inner and outer myometrium were analysed using a pharmacokinetic model. These parameters were tissue blood flow (F), blood volume fraction (V{sub b}), permeability-surface area product (PS), interstitial volume fraction (V{sub e}) and lag time (Dt). In the women of reproductive age, the inner myometrium displayed higher F and PS, lower V{sub b} and V{sub e}, and longer Dt than the outer myometrium (p = 0.02, p = 0.01, p = 0.005, p = 0.03 and p = 0.01, respectively). The inner myometrium presented microvascular variations during the menstrual cycle with a pre-ovulatory peak followed by a fall reaching a nadir of F and V{sub b} about 4 days after ovulation. Compared with women of reproductive age, in the postmenopausal state, F and V{sub b} decreased in the outer myometrium, while PS, V{sub e} and Dt increased (p < 0.0001, p = 0.001, p = 0.001, p = 0.03 and p = 0.0004, respectively). DCE-MRI is a non-invasive technique that can measure variations of myometrial microcirculation, and thereby be potentially useful to help characterize the role and states of the myometrium in assisted reproductive therapy. (orig.)

  9. Cell uptake mechanisms of PAMAM G4-FITC dendrimer in human myometrial cells

    Energy Technology Data Exchange (ETDEWEB)

    Oddone, Natalia; Zambrana, Ana I.; Tassano, Marcos [Instituto de Investigaciones Biologicas Clemente Estable, Laboratorio de Senalizacion Celular y Nanobiologia (Uruguay); Porcal, Williams [Universidad de la Republica, Grupo de Quimica Medicinal, Instituto de Quimica Biologica, Facultad de Ciencias-Facultad de Quimica (Uruguay); Cabral, Pablo [Universidad de la Republica, Laboratorio de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias (Uruguay); Benech, Juan C., E-mail: benech@iibce.edu.uy [Instituto de Investigaciones Biologicas Clemente Estable, Laboratorio de Senalizacion Celular y Nanobiologia (Uruguay)

    2013-07-15

    The high incidence and severity of diseases which involve smooth muscle dysfunction dictates the need of continued search for novel therapeutic strategies to treat these conditions. Dendrimers are branched macromolecules with multiple end-groups that can be functionalized for applications which include drug delivery. There is no data regarding the cellular uptake mechanisms used by dendrimers in smooth muscle human myometrial cells (HMC). Polyamidoamine G4 dendrimers were conjugated with fluorescein isothiocyanate (FITC) and the resulting conjugate (G4-FITC) was characterized using high-performance liquid chromatography, nuclear magnetic resonance, and atomic force microscopy. G4-FITC showed to have no significant effect on the primary culture HMC viability up to 48 h. HMC incubated with G4-FITC were analyzed by laser confocal microscopy. Peri-nuclear fluorescence distribution was observed at 5 h of incubation or more (24, 36, and 48 h). At 24 h, G4-FITC partially co-localized with lysotracker. Uptake of G4-FITC by HMC was slightly inhibited by filipin (8.0 {+-} 3.9 %) and significantly inhibited by chlorpromazine (63.5 {+-} 3.7 %). In non-electroporated HMC, G4-FITC was never observed inside the cell nucleus. Interestingly, we detected G4-FITC inside the nuclear domain of some electroporated cells. Thus, electroporation changed intracellular G4-FITC localization. Isolated nuclei of HMC incubated with G4-FITC showed fluorescence signal inside the nuclear domain. The results suggest that in HMC, G4-FITC is taken up by clathrin-mediated endocytosis with endosomal and lysosomal localization at 24 h. The combination of electroporation and dendrimers could be an interesting technology to electrotransfer drugs into smooth muscle cells cytosol and nuclei.

  10. Cardiac myofibrillar contractile properties during the progression from hypertension to decompensated heart failure.

    Science.gov (United States)

    Hanft, Laurin M; Emter, Craig A; McDonald, Kerry S

    2017-07-01

    Heart failure arises, in part, from a constellation of changes in cardiac myocytes including remodeling, energetics, Ca 2+ handling, and myofibrillar function. However, little is known about the changes in myofibrillar contractile properties during the progression from hypertension to decompensated heart failure. The aim of the present study was to provide a comprehensive assessment of myofibrillar functional properties from health to heart disease. A rodent model of uncontrolled hypertension was used to test the hypothesis that myocytes in compensated hearts exhibit increased force, higher rates of force development, faster loaded shortening, and greater power output; however, with progression to overt heart failure, we predicted marked depression in these contractile properties. We assessed contractile properties in skinned cardiac myocyte preparations from left ventricles of Wistar-Kyoto control rats and spontaneous hypertensive heart failure (SHHF) rats at ~3, ~12, and >20 mo of age to evaluate the time course of myofilament properties associated with normal aging processes compared with myofilaments from rats with a predisposition to heart failure. In control rats, the myofilament contractile properties were virtually unchanged throughout the aging process. Conversely, in SHHF rats, the rate of force development, loaded shortening velocity, and power all increased at ~12 mo and then significantly fell at the >20-mo time point, which coincided with a decrease in left ventricular fractional shortening. Furthermore, these changes occurred independent of changes in β-myosin heavy chain but were associated with depressed phosphorylation of myofibrillar proteins, and the fall in loaded shortening and peak power output corresponded with the onset of clinical signs of heart failure. NEW & NOTEWORTHY This novel study systematically examined the power-generating capacity of cardiac myofilaments during the progression from hypertension to heart disease. Previously

  11. Cadmium translocation by contractile roots differs from that in regular, non-contractile roots.

    Science.gov (United States)

    Lux, Alexander; Lackovič, Andrej; Van Staden, Johannes; Lišková, Desana; Kohanová, Jana; Martinka, Michal

    2015-06-01

    Contractile roots are known and studied mainly in connection with the process of shrinkage of their basal parts, which acts to pull the shoot of the plant deeper into the ground. Previous studies have shown that the specific structure of these roots results in more intensive water uptake at the base, which is in contrast to regular root types. The purpose of this study was to find out whether the basal parts of contractile roots are also more active in translocation of cadmium to the shoot. Plants of the South African ornamental species Tritonia gladiolaris were cultivated in vitro for 2 months, at which point they possessed well-developed contractile roots. They were then transferred to Petri dishes with horizontally separated compartments of agar containing 50 µmol Cd(NO3)2 in the region of the root base or the root apex. Seedlings of 4-d-old maize (Zea mays) plants, which do not possess contractile roots, were also transferred to similar Petri dishes. The concentrations of Cd in the leaves of the plants were compared after 10 d of cultivation. Anatomical analyses of Tritonia roots were performed using appropriately stained freehand cross-sections. The process of contraction required specific anatomical adaptation of the root base in Tritonia, with less lignified and less suberized tissues in comparison with the subapical part of the root. These unusual developmental characteristics were accompanied by more intensive translocation of Cd ions from the basal part of contractile roots to the leaves than from the apical-subapical root parts. The opposite effects were seen in the non-contractile roots of maize, with higher uptake and transport by the apical parts of the root and lower uptake and transport by the basal part. The specific characteristics of contractile roots may have a significant impact on the uptake of ions, including toxic metals from the soil surface layers. This may be important for plant nutrition, for example in the uptake of nutrients from

  12. Effects of Silodosin and Tamsulosin on the Seminal Vesicle Contractile Response.

    Science.gov (United States)

    Hayashi, Tokumasa; Takeya, Mitsue; Nakamura, Kei-ichiro; Matsuoka, Kei

    2016-01-01

    To understand the mechanisms underlying ejaculation dysfunction caused by α1A-adrenocetor (AR) antagonists, the effects of α1A-AR antagonists on the contractile responses of the seminal vesicle were investigated. Isolated seminal vesicles from guinea pigs were cannulated and pressurized, and the changes in the intraluminal pressure were recorded. Periodic applications of electrical stimulation (ES) caused biphasic increase in the intraluminal pressure, that is, initial and subsequent contractions. The effects of silodosin and tamsulosin, α1A-AR antagonists, on the contractile responses were examined. The ES-induced biphasic contractions were blocked by tetrodotoxin (TTX). Silodosin and tamsulosin suppressed the initial contractions in a dose-dependent manner, while also exerting various inhibitory effects on the subsequent contractions. Increases in the intraluminal pressure facilitated spontaneous phasic contractions. The spontaneous contractions were not affected by TTX or α1A-AR antagonists, but were abolished by nifedipine. The initial contractions triggered by neuronal excitations were suppressed by silodosin and tamsulosin, suggesting that the ejaculation dysfunction may be attributed to the α1A-AR antagonist-mediated suppression of nerve-evoked contractions in the seminal vesicle. The subsequent contractions may be induced by mechanical stimulation associated with the initial, nerve-evoked contractions. Alternatively, other transmitters may be involved to various degrees in the neuromuscular transmission of the seminal vesicle. © 2014 Wiley Publishing Asia Pty Ltd.

  13. Transvaginal ultrasound assessment of myometrial and cervical stroma invasion in women with endometrial cancer -interobserver reproducibility among ultrasound experts and gynaecologists

    DEFF Research Database (Denmark)

    Eriksson, LS; Lindqvist, PG; Flöter Rådestad, A

    2014-01-01

    OBJECTIVES: To assess interobserver reproducibility among ultrasound experts and gynaecologists in the prediction of deep myometrial- and cervical stroma invasion by transvaginal ultrasound in women with endometrial cancer. METHODS: Video-clips of the corpus- and cervix uteri of 53 women...... with endometrial cancer, examined preoperatively by the same ultrasound expert, were integrated in a digitalized survey. Nine ultrasound experts and 9 gynaecologists evaluated presence or absence of deep myometrial- and cervical stroma invasion. Histopathology from hysterectomy specimen was used as gold standard.......001). CONCLUSION: Preoperative ultrasound assessment of deep myometrial- and cervical stroma invasion in endometrial cancer is best performed by ultrasound experts, as they show a higher degree of agreement to histopathology and higher interobserver reproducibility in the assessment of cervical stromal invasion....

  14. 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.

  15. Assessment of deep myometrial invasion of endometrial cancer on MRI: added value of second-opinion interpretations by radiologists subspecialized in gynaecologic oncology.

    Science.gov (United States)

    Woo, Sungmin; Kim, Sang Youn; Cho, Jeong Yeon; Kim, Seung Hyup

    2017-05-01

    To investigate the added value of secondary reports issued by radiologists subspecializing in gynaecologic imaging for determining deep myometrial invasion of endometrial cancer on MRI. Initial (from referring institutions) and secondary (by subspecialized radiologists) interpretations of MRI of 55 patients with endometrial cancer were retrospectively reviewed. A radiologist blinded to clinicopathological information assessed both reports for the presence of deep myometrial invasion. Reference standard was based on hysterectomy specimens. Kappa coefficients (k) were used to measure their concordance. McNemar testing and receiver operating characteristic (ROC) analysis was used to compare sensitivities, specificities and areas under the curves (AUCs). Deep myometrial invasion was present in 25 (45.5 %) patients. Among 27.3 % (15/55; k = 0.458) patients with discrepant results, secondary interpretations were correct in 10 (66.7 %) cases. Sensitivity was higher in secondary than in initial reports (76.0 % vs. 48.0 %, p = 0.039) while no significant difference was seen in specificity (70.0 % vs. 76.7 %, p = 0.668). At ROC analysis, there was a tendency for higher AUCs in secondary reports (0.785 vs 0.669, p = 0.096). Secondary readings of MRI by subspecialized gynaecologic oncologic radiologists may provide incremental value in determining deep myometrial invasion of endometrial cancer. • Deep myometrial invasion is an important prognostic factor in endometrial cancer. • Assessment of deep myometrial invasion is often discrepant between initial and secondary reports. • Secondary reports showed higher sensitivity and accuracy. • Secondary review of MRI may provide incremental value in endometrial cancer patients.

  16. Predictive value of T2-weighted imaging and contrast-enhanced MR imaging in assessing myometrial invasion in endometrial cancer: a pooled analysis of prospective studies

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Lian-Ming [Shanghai Jiao Tong University School of Medicine, Department of Radiology, Renji Hospital, Shanghai (China); Wayne State University, Department of Radiology, Detroit, MI (United States); Xu, Jian-Rong; Gu, Hai-Yan; Hua, Jia [Shanghai Jiao Tong University School of Medicine, Department of Radiology, Renji Hospital, Shanghai (China); Haacke, E.M.; Hu, Jiani [Wayne State University, Department of Radiology, Detroit, MI (United States)

    2013-02-15

    To obtain diagnostic performance values of T2-weighted imaging (T2WI) and contrast-enhanced magnetic resonance imaging (CE-MRI) in the prediction of myometrial invasion in patients with endometrial cancer. Databases including MEDLINE and EMBASE were searched for relevant original articles published from January1995 to March 2012. Pooled estimation data were obtained by statistical analysis. Eleven articles (548 patients) were included. For assessing any myometrial involvement, the pooled sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for CE-MRI were 0.81 (95% CI, 0.72, 0.88), 0.72 (95% CI, 0.64, 0.79), 0.65 (95% CI, 0.56, 0.73) and 0.85 (95% CI, 0.78, 0.91); for T2WI, they were 0.87 (95% CI, 0.78, 0.94), 0.58 (95% CI, 0.47, 0.69), 0.64 (95% CI, 0.54, 0.73), 0.84 (95% CI, 0.73, 0.92) respectively. The pooled specificity of CE-MRI (0.72) was significantly higher than T2WI (0.58) (P < 0.05). For assessing deep myometrial involvement, there was no statistically significant difference between CE-MRI and T2WI, (P > 0.05). CE-MRI has a good diagnostic performance in the prediction of any myometrial invasion and is superior to T2WI. But its PPV is somewhat suboptimal. For assessing deep myometrial involvement, its NPV appears relative high and negative findings strongly suggest an absence of deep myometrial involvement, which can guide therapeutic decision-making. (orig.)

  17. The adverse effects of aldrin and dieldrin on both myometrial contractions and the secretory functions of bovine ovaries and uterus in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Wrobel, Michał H., E-mail: m.wrobel@pan.olsztyn.pl; Grzeszczyk, Marlena; Mlynarczuk, Jaroslaw; Kotwica, Jan

    2015-05-15

    Aldrin and dieldrin are chloroorganic insecticides which are recognised as endocrine disruptors. The aim of the study was to investigate their effect on the secretory functions of the uterus and ovary and on myometrial contractions. Myometrial strips and uterine and ovarian cells from nonpregnant cows were incubated with the xenobiotics (0.1, 1 or 10 ng/ml) for 24 or 72 h. Next, their effect on viability of myometrial, endometrial, granulosa and luteal cells, myometrial strip contractions, the synthesis and secretion of prostaglandins (PGs: PGF2α and PGE2) from uterine cells, the secretion of oestradiol (E2), testosterone (T) and oxytocin (OT) from granulosa cells and the secretion of progesterone (P4) and OT from luteal cells were determined. Neither of the xenobiotics (10 ng/ml) affected (P > 0.05) the viability of the ovarian and uterine cells, while both (0.1–10 ng/ml) decreased (P < 0.05) the basal and OT-stimulated myometrial contractions. In spite of these effects, neither of the insecticides affected (P > 0.05) the synthesis and the secretion of PGs from the myometrial cells. Although they also did not impair the secretion of the PGs from the endometrial cells, they abolished (P < 0.05) the stimulatory effect of OT (P < 0.05) on the secretion of the PGs and stimulated (P < 0.05) the secretion of OT from the granulosa and luteal cells. Moreover, aldrin and dieldrin stimulated secretion of E2 and T from the granulosa cells, while only dieldrin increased (P < 0.05) the secretion of P4 from luteal cells. The data show that aldrin and dieldrin stimulated the secretory function of the cultured granulosa and luteal cells and inhibited the myometrial contractions of cows in vitro, which may affect on natural parturition. - Highlights: • Aldrin and dieldrin inhibited bovine myometrial contractions. • The studied xenobiotics stimulated steroids and oxytocin secretion from ovaries. • Prostaglandins are not involved in adverse effect of the xenobiotics on

  18. Considerations for Contractile Electroactive Materials and Actuators

    Energy Technology Data Exchange (ETDEWEB)

    Lenore Rasmussen, David Schramm, Paul Rasmussen, Kevin Mullaly, Ras Labs, LLC, Intelligent Materials for Prosthetics & Automation, Lewis D. Meixler, Daniel Pearlman and Alice Kirk

    2011-05-23

    Ras Labs produces contractile electroactive polymer (EAP) based materials and actuators that bend, swell, ripple, and contract (new development) with low electric input. In addition, Ras Labs produces EAP materials that quickly contract and expand, repeatedly, by reversing the polarity of the electric input, which can be cycled. This phenomenon was explored using molecular modeling, followed by experimentation. Applied voltage step functions were also investigated. High voltage steps followed by low voltage steps produced a larger contraction followed by a smaller contraction. Actuator control by simply adjusting the electric input is extremely useful for biomimetic applications. Muscles are able to partially contract. If muscles could only completely contract, nobody could hold an egg, for example, without breaking it. A combination of high and low voltage step functions could produce gross motor function and fine manipulation within the same actuator unit. Plasma treated electrodes with various geometries were investigated as a means of providing for more durable actuation.

  19. Genome sequence of Haloplasma contractile, an unusual contractile bacterium from a deep-sea anoxic brine lake.

    KAUST Repository

    Antunes, Andre

    2011-09-01

    We present the draft genome of Haloplasma contractile, isolated from a deep-sea brine and representing a new order between Firmicutes and Mollicutes. Its complex morphology with contractile protrusions might be strongly influenced by the presence of seven MreB/Mbl homologs, which appears to be the highest copy number ever reported.

  20. Effects of Crocetin Esters and Crocetin from Crocus sativus L. on Aortic Contractility in Rat Genetic Hypertension

    Directory of Open Access Journals (Sweden)

    Silvia Llorens

    2015-09-01

    Full Text Available Background: Endothelial dysfunction, characterized by an enhancement in vasoconstriction, is clearly associated with hypertension. Saffron (Crocus sativus L. bioactive compounds have been recognized to have hypotensive properties. Recently, we have reported that crocetin exhibits potent vasodilator effects on isolated aortic rings from hypertensive rats. In this work, we have aimed to analyze the anticontractile ability of crocetin or crocetin esters pool (crocins isolated from saffron. Thus, we have studied the effects of saffron carotenoids on endothelium-dependent and -independent regulation of smooth muscle contractility in genetic hypertension. Methods: We have measured the isometric responses of aortic segments with or without endothelium obtained from spontaneously hypertensive rats. The effects of carotenoids were studied by assessing the endothelial modulation of phenylephrine-induced contractions (10−9–10−5 M in the presence or absence of crocetin or crocins. The role of nitric oxide and prostanoids was analyzed by performing the experiments with L-NAME (NG-nitro-l-arginine methyl ester or indomethacin (both 10−5 M, respectively. Results: Crocetin, and to a minor extent crocins, diminished the maximum contractility of phenylephrine in intact rings, while crocins, but not crocetin, increased this contractility in de-endothelizated vessels. In the intact vessels, the effect of crocetin on contractility was unaffected by indomethacin but was abolished by L-NAME. However, crocetin but not crocins, lowered the already increased contractility caused by L-NAME. Conclusions: Saffron compounds, but especially crocetin have endothelium-dependent prorelaxing actions. Crocins have procontractile actions that take place via smooth muscle cell mechanisms. These results suggest that crocetin and crocins activate different mechanisms involved in the vasoconstriction pathway in hypertension.

  1. Parasympathetic neurons in the cranial medial ventricular fat pad on the dog heart selectively decrease ventricular contractility.

    Science.gov (United States)

    Dickerson, L W; Rodak, D J; Fleming, T J; Gatti, P J; Massari, V J; McKenzie, J C; Gillis, R A

    1998-05-28

    We hypothesized that selective control of ventricular contractility might be mediated by postganglionic parasympathetic neurons in the cranial medial ventricular (CMV) ganglion plexus located in a fat pad at the base of the aorta. Sinus rate, atrioventricular (AV) conduction (ventricular rate during atrial pacing), and left ventricular contractile force (LV dP/dt during right ventricular pacing) were measured in eight chloralose-anesthetized dogs both before and during bilateral cervical vagus stimulation (20-30 V, 0.5 ms pulses, 15-20 Hz). Seven of these dogs were tested under beta-adrenergic blockade (propranolol, 0.8 mg kg(-1) i.v.). Control responses included sinus node bradycardia or arrest during spontaneous rhythm, high grade AV block or complete heart block, and a 30% decrease in contractility from 2118 +/- 186 to 1526 +/- 187 mm Hg s(-1) (P 0.05) decrease in contractility but still elicited the same degree of sinus bradycardia and AV block (N = 8, P < 0.05). Five dogs were re-tested 3 h after trimethaphan fat pad injection, at which time blockade of vagally-induced negative inotropy was partially reversed, as vagal stimulation decreased LV dP/dt by 19%. The same dose of trimethaphan given either locally into other fat pads (PVFP or IVC-ILA) or systemically (i.v.) had no effect on vagally-induced negative inotropy. Thus, parasympathetic ganglia located in the CMV fat pad mediated a decrease in ventricular contractility during vagal stimulation. Blockade of the CMV fat pad had no effect on vagally-mediated slowing of sinus rate or AV conduction.

  2. Assessment of deep myometrial invasion of endometrial cancer on MRI: added value of second-opinion interpretations by radiologists subspecialized in gynaecologic oncology

    Energy Technology Data Exchange (ETDEWEB)

    Woo, Sungmin [Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Kim, Sang Youn [Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Cho, Jeong Yeon; Kim, Seung Hyup [Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Seoul National University Medical Research Center, Institute of Radiation Medicine and Kidney Research Institute, Seoul (Korea, Republic of)

    2017-05-15

    To investigate the added value of secondary reports issued by radiologists subspecializing in gynaecologic imaging for determining deep myometrial invasion of endometrial cancer on MRI. Initial (from referring institutions) and secondary (by subspecialized radiologists) interpretations of MRI of 55 patients with endometrial cancer were retrospectively reviewed. A radiologist blinded to clinicopathological information assessed both reports for the presence of deep myometrial invasion. Reference standard was based on hysterectomy specimens. Kappa coefficients (k) were used to measure their concordance. McNemar testing and receiver operating characteristic (ROC) analysis was used to compare sensitivities, specificities and areas under the curves (AUCs). Deep myometrial invasion was present in 25 (45.5 %) patients. Among 27.3 % (15/55; k = 0.458) patients with discrepant results, secondary interpretations were correct in 10 (66.7 %) cases. Sensitivity was higher in secondary than in initial reports (76.0 % vs. 48.0 %, p = 0.039) while no significant difference was seen in specificity (70.0 % vs. 76.7 %, p = 0.668). At ROC analysis, there was a tendency for higher AUCs in secondary reports (0.785 vs 0.669, p = 0.096). Secondary readings of MRI by subspecialized gynaecologic oncologic radiologists may provide incremental value in determining deep myometrial invasion of endometrial cancer. (orig.)

  3. Impaired recovery of intracellular calcium and force after activation in isolated myometrial and subcutaneous resistance arteries from women with preeclampsia.

    Science.gov (United States)

    Wimalasundera, Ruwan C; Wijetunge, Sumangali; Thom, Simon M; Regan, Lesley; Hughes, Alun D

    2010-03-01

    Preeclampsia is a major cause of maternal and perinatal morbidity and mortality, but its cause is poorly understood. This study investigated whether there is an abnormality of intracellular calcium ([Ca2=]i) and tension during recovery from activation in isolated resistance arteries in preeclampsia and investigated the underlying mechanisms. Subcutaneous and myometrial resistance arteries from preeclamptic, normotensive pregnant and nonpregnant women were mounted on an isometric myograph and loaded with fura-2 to allow simultaneous measurement of force and [Ca2+]i. Arteries were activated by a high-potassium solution or noradrenaline, and the rate of decline in force and [Ca2+]i examined following washout. Basal tone and [Ca2+]i and rise in force and [Ca2+]i induced by high-potassium solution did not differ between groups but the rate of decline after washout was significantly slowed in both subcutaneous and myometrial arteries from preeclamptic women as compared with normotensive pregnant or nonpregnant women. The rate of decline in force after noradrenaline was also slowed in arteries from preeclamptic women. In subcutaneous resistance arteries from nonpregnant women, removal of the endothelium did not affect the rate of decline in force after high-potassium solution. However, inhibition of the plasma membrane Ca ATPase with carboxyeosin mimicked the findings seen in preeclampsia. In contrast, inhibition of the sarcoplasmic endoreticulum Ca ATPase with cyclopiazonic acid had no effect on the rate of decline in force or [Ca2+]i. The rate of relaxation and decline in [Ca2+]i in resistance arteries are impaired in preeclampsia. This may be mediated by decreased activity of plasma membrane Ca2+ ATPase and could be a mechanism contributing to elevated peripheral resistance and raised blood pressure in preeclampsia.

  4. Considerations for Contractile Electroactive Materials and Actuators

    Energy Technology Data Exchange (ETDEWEB)

    Rasmussen, Lenore; Erickson, Carl J.; Meixler, Lewis D.; Ascione, George; Gentile, Charles A.; Tilson, Carl; Bernasek, Stephen L.; Abelev, Esta

    2010-02-19

    Ras Labs produces electroactive polymer (EAP) based materials and actuators that bend, swell, ripple and now contract (new development) with low electric input. This is an important attribute because of the ability of contraction to produce life-like motion. The mechanism of contraction is not well understood. Radionuclide-labeled experiments were conducted to follow the movement of electrolytes and water in these EAPs when activated. Extreme temperature experiments were performed on the contractile EAPs with very favorable results. One of the biggest challenges in developing these actuators, however, is the electrode-EAP interface because of the pronounced movement of the EAP. Plasma treatments of metallic electrodes were investigated in order to improve the attachment of the embedded electrodes to the EAP material. Surface analysis, adhesive testing, and mechanical testing were conducted to test metal surfaces and metal-polymer interfaces. The nitrogen plasma treatment of titanium produced a strong metal-polymer interface; however, oxygen plasma treatment of both stainless steel and titanium produced even stronger metal-polymer interfaces. Plasma treatment of the electrodes allows for the embedded electrodes and the EAP material of the actuator to work and move as a unit, with no detachment, by significantly improving the metal-polymer interface.

  5. Geometrical Origins of Contractility in Disordered Actomyosin Networks

    Directory of Open Access Journals (Sweden)

    Martin Lenz

    2014-10-01

    Full Text Available Movement within eukaryotic cells largely originates from localized forces exerted by myosin motors on scaffolds of actin filaments. Although individual motors locally exert both contractile and extensile forces, large actomyosin structures at the cellular scale are overwhelmingly contractile, suggesting that the scaffold serves to favor contraction over extension. While this mechanism is well understood in highly organized striated muscle, its origin in disordered networks such as the cell cortex is unknown. Here, we develop a mathematical model of the actin scaffold’s local two- or three-dimensional mechanics and identify four competing contraction mechanisms. We predict that one mechanism dominates, whereby local deformations of the actin break the balance between contraction and extension. In this mechanism, contractile forces result mostly from motors plucking the filaments transversely rather than buckling them longitudinally. These findings shed light on recent in vitro experiments and provide a new geometrical understanding of contractility in the myriad of disordered actomyosin systems found in vivo.

  6. [Inotropic effect of a new probiotic product on myocardial contractility. Comparison with diazoxide].

    Science.gov (United States)

    Sobol', K V; Korotkov, S M; Nesterov, V P

    2014-01-01

    The inotropic effect of a new probiotic product on myocardial contractility of the frog Rana ridibunda and the effect of probiotic product on the rat cardiac mitochondria swelling were studied. In both cases, the comparison with known cardioprotector diazoxide was done. Probiotic product and diazoxide were shown to cause a dual effect on the maximum force induced by the muscle sample during spontaneous atrial contraction. Addition of agents caused a negative impact, while washing out exerted a positive inotropic effect. At the same time probiotic product has virtually no effect on the amplitude of contraction induced by electrical stimulation of the ventricle fragments. Probiotic product decreases both proton passive permeability in the inner mitochondrial membrane, and potassium active transport in mitochondria caused by activation of K(+)-uniporter of cardiomyocytes. A possible mechanism of action of probiotic product is discussed.

  7. MRI evaluation of myometrial invasion by endometrial carcinoma. Comparison between fast-spin-echo T2W and coronal FMPSPGR Gadolinium-Dota-Enhanced Sequences

    International Nuclear Information System (INIS)

    Nasi, Francesca; Fiocchi, Federica; Pecchi, Annarita; Torricelli, Pietro; Rivasi, Francesco

    2005-01-01

    Purpose. The depth of myometrial invasion by endometrial carcinoma strongly affects the incidence of metastasis to regional nodes and influences the surgical strategies. The aim of this paper is to compare the results of FSE T2-w and Gadolinium-enhanced FMPSGR MR sequences in assessing the depth of myometrial invasion by endometrial cancer. Materials and methods. Forty-five women with histopathologically-proven endometrial carcinoma underwent preoperative MRI. Axial SE TI w, axial, sagittal and para-coronal FSE T2w and para-coronal Gadolinium enhanced FMPSGR sequences were performed using a high field strength magnet (1.5T). Within one month of MR all patients underwent hysterectomy, and anatomical evaluation of the surgical specimen was done sectioning the uterus along the short axis. Based upon the results of the histological evaluation the results of the FSE T2w and Gadolinium-enhanced sequences were compared and the statistical difference between the results obtained was statistically evaluated. Results. The histological evaluation showed intra mucosal neoplasm in 11 patients, myometrial infiltration less than 50% in 31 patients, myometrial infiltration more than 50% in 12 patients and transmural cancer 1 patient. Statistical evaluation showed that the FSE T2w sequence had a global sensitivity and specificity of 80.6% and 87.6%, respectively, with a mean Negative Predictive Value of 92.6% and a mean Positive Predictive Value of 86%. Gadolinium-enhanced FMPSPGR sequence had a global sensitivity and specificity of 90.6% and 93.3%, respectively, with a mean Negative Predictive Value of 96,3% and a mean Positive Predictive Value of 88%. The staging accuracy (χ 2 test) on FMPSPGR images (95%) was higher than that on FSE T2w images (78%). Conclusions. In our experience Gadolinium-enhanced dynamic sequences increase the accuracy of MR imaging in diagnosing the depth of myometrial invasion. In particular they improve the visualisation of the inner myometrium, the so

  8. Actin in dividing cells: contractile ring filaments bind heavy meromyosin.

    Science.gov (United States)

    Schroeder, T E

    1973-06-01

    Many microfilaments and microtubules are well preserved after glycerol-extraction of HeLa cells at room temperature (22 degrees ). Incubation in heavy meromyosin from rabbit skeletal muscle results in conspicuous and characteristic "decoration" of microfilaments of the contractile ring. Decoration is completely prevented by 10 mM ATP or 2 mM pyrophosphate, and fails to occur if heavy meromyosin is either omitted or replaced by egg albumin, a nonspecific protein. Decorated microfilaments have a substructure consisting of polarized, repeating arrowheads 27-35 nm apart. The specificity of these results strongly suggests that microfilaments of the contractile ring in HeLa cells are closely related to muscle actin. Very thin undecorated strands among the microfilaments of the contractile ring possibly represent a myosin component. These findings are discussed in terms of: the actomyosin-like properties of the contractile ring as a mechanochemical organelle that causes cell cleavage; the probable universal occurrence of actin-like protein in all dividing animal cells; and the contractile ring's combined sensitivity to cytochalasin B and its affinity for heavy meromyosin, a combination unique among microfilamentous organelles.

  9. Clinical Outcomes in International Federation of Gynecology and Obstetrics Stage IA Endometrial Cancer With Myometrial Invasion Treated With or Without Postoperative Vaginal Brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Diavolitsis, V. [Department of Radiation Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL (United States); Rademaker, A. [Department of Preventive Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL (United States); Lurain, J.; Hoekstra, A. [Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL (United States); Strauss, J. [Department of Radiation Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL (United States); Small, W., E-mail: wsmall@nmff.org [Department of Radiation Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL (United States)

    2012-10-01

    Purpose: To assess the clinical outcomes of patients with Stage IA endometrial cancer with myometrial invasion treated with postoperative vaginal brachytherapy (VBT) with those who received no adjuvant therapy (NAT). Methods and Materials: All patients treated with hysterectomy for endometrial cancer at Northwestern Memorial Hospital between 1978 and 2005 were identified. Those patients with Stage IA disease with myometrial invasion who were treated with VBT alone or NAT were identified and included in the present analysis. Results: Of 252 patients with Stage IA endometrial cancer with superficial (<50%) myometrial invasion who met the inclusion criteria, 169 underwent VBT and 83 received NAT. The median follow-up in the VBT and NAT groups was 103 and 61 months, respectively. In the VBT group, 56.8% had Grade 1, 37.9% had Grade 2, and 5.3% had Grade 3 tumors. In the NAT group, 75.9%, 20.5%, and 3.6% had Grade 1, 2, and 3 tumors, respectively. Lymphatic or vascular space invasion was noted in 12.4% of the VBT patients and 5.6% of the NAT patients. The 5-year overall survival rate was 95.5%. The 5-year recurrence-free survival rate was 92.4% for all patients, 94.4% for the VBT group, and 87.4% for the NAT group (p = NS). Of the 169 VBT patients and 83 NAT patients, 8 (4.7%) and 6 (7.2%) developed recurrent disease. One vaginal recurrence occurred in the VBT group (0.6%) and three in the NAT group (3.8%). Recurrences developed 2-102 months after surgical treatment. Two of the four vaginal recurrences were salvaged. No Grade 3 or higher acute or late radiation toxicity was noted. Conclusions: The use of postoperative VBT in patients with Stage I endometrial cancer with <50% myometrial invasion yielded excellent vaginal disease control and disease-free survival, with minimal toxicity.

  10. Primary Human Uterine Leiomyoma Cell Culture Quality Control: Some Properties of Myometrial Cells Cultured under Serum Deprivation Conditions in the Presence of Ovarian Steroids.

    Directory of Open Access Journals (Sweden)

    Camila Bonazza

    Full Text Available Cell culture is considered the standard media used in research to emulate the in vivo cell environment. Crucial in vivo experiments cannot be conducted in humans and depend on in vitro methodologies such as cell culture systems. However, some procedures involving the quality control of cells in culture have been gradually neglected by failing to acknowledge that primary cells and cell lines change over time in culture. Thus, we report methods based on our experience for monitoring primary cell culture of human myometrial cells derived from uterine leiomyoma. We standardized the best procedure of tissue dissociation required for the study of multiple genetic marker systems that include species-specific antigens, expression of myofibroblast or myoblast markers, growth curve, serum deprivation, starvation by cell cycle synchronization, culture on collagen coated plates, and 17 β-estradiol (E2 and progesterone (P4 effects. The results showed that primary myometrial cells from patients with uterine leiomyoma displayed myoblast phenotypes before and after in vitro cultivation, and leiomyoma cells differentiated into mature myocyte cells under the appropriate differentiation-inducing conditions (serum deprivation. These cells grew well on collagen coated plates and responded to E2 and P4, which may drive myometrial and leiomyoma cells to proliferate and adhere into a focal adhesion complex involvement in a paracrine manner. The establishment of these techniques as routine procedures will improve the understanding of the myometrial physiology and pathogenesis of myometrium-derived diseases such as leiomyoma. Mimicking the in vivo environment of fibrotic conditions can prevent false results and enhance results that are based on cell culture integrity.

  11. Effect of serotonin on small intestinal contractility in healthy volunteers

    DEFF Research Database (Denmark)

    Hansen, M.B.; Arif, F.; Gregersen, H.

    2008-01-01

    -duodeno-jejunal contractility in healthy human volunteers. Manometric recordings were obtained and the effects of either a standard meal, continuous intravenous infusion of serotonin (20 nmol/kg/min) or intraluminal bolus infusions of graded doses of serotonin (2.5, 25 or 250 nmol) were compared. In addition, platelet......-depleted plasma levels of serotonin, blood pressure, heart rate and electrocardiogram were evaluated. All subjects showed similar results. Intravenous serotonin increased migrating motor complex phase In frequency 3-fold and migrating velocity 2-fold. Intraluminal infusion of serotonin did not change contractile...

  12. Contractile injection systems of bacteriophages and related systems

    DEFF Research Database (Denmark)

    Taylor, Nicholas M I; van Raaij, Mark J; Leiman, Petr G

    2018-01-01

    through the target cell membrane. Subsequently, the bacteriophage genome is injected through the tube. The structural transformation of the bacteriophage T4 baseplate upon binding to the host cell has been recently described in near-atomic detail. In this review we discuss structural elements and features...... of this mechanism that are likely to be conserved in all contractile injection systems (systems evolutionary and structurally related to contractile bacteriophage tails). These include the type VI secretion system (T6SS), which is used by bacteria to transfer effectors into other bacteria and into eukaryotic cells...

  13. Comparison of contractile and extensile pneumatic artificial muscles

    Science.gov (United States)

    Pillsbury, Thomas E.; Wereley, Norman M.; Guan, Qinghua

    2017-09-01

    Pneumatic artificial muscles (PAMs) are used in robotic and prosthetic applications due to their high power to weight ratio, controllable compliance, and simple design. Contractile PAMs are typically used in traditional hard robotics in place of heavy electric motors. As the field of soft robotics grows, extensile PAMs are beginning to have increased usage. This work experimentally tests, models, and compares contractile and extensile PAMs to demonstrate the advantages and disadvantages of each type of PAM and applications for which they are best suited.

  14. Adherent basal plate myometrial fibers in the delivered placenta as a risk factor for development of subsequent placenta accreta.

    Science.gov (United States)

    Linn, Rebecca L; Miller, Emily S; Lim, Grace; Ernst, Linda M

    2015-12-01

    Placenta accreta is implantation of chorionic tissue directly upon the myometrium without normal intervening decidua. The clinical significance of myometrial fibers attached to the basal plate (BPMYO) has yet to be fully elucidated. To determine the importance of depth and quantity of BPMYO in predicting subsequent accreta in the next pregnancy. Women with placentas from two successive pregnancies submitted for pathologic evaluation were included. 50 cases had clinical and/or pathologic diagnosis of accreta in an index pregnancy. 100 controls had no evidence of accreta in an index pregnancy. H&E slides were re-reviewed and stage of accreta/BPMYO was determined. The stages were defined as: Stage 0-no BPMYO; Stage 1-BPMYO with intervening decidua; Stage 2 placenta was quantified. Prior placentas of cases were twice as likely to have BPMYO compared to controls (84%vs42%, P placenta (38%vs2%, P placenta are significantly associated with the subsequent development of accreta. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Spontaneous pneumothorax in weightlifters.

    Science.gov (United States)

    Marnejon, T; Sarac, S; Cropp, A J

    1995-06-01

    Spontaneous pneumothorax is infrequently caused by strenuous exertion. To our knowledge there has only been one case of spontaneous pneumothorax associated with weightlifting reported in the medical literature. We describe three consecutive cases of spontaneous pneumothorax associated with weightlifting. We postulate that spontaneous pneumothorax in these patients may be secondary to improper breathing techniques. It is important that physicians and weight trainers be aware of the association between weight lifting and spontaneous pneumothorax and assure that proper instruction is given to athletes who work with weights.

  16. Different roles of alpha2-adrenoceptor subtypes in non-pregnant and late-pregnant uterine contractility in vitro in the rat.

    Science.gov (United States)

    Gáspár, Róbert; Gál, Adrienn; Gálik, Márta; Ducza, Eszter; Minorics, Renáta; Kolarovszki-Sipiczki, Zoltán; Klukovits, Anna; Falkay, George

    2007-10-01

    The roles of the alpha2-adrenoceptor (alpha2-AR) subtypes (alpha2A-, alpha2B- and alpha2C-AR) in uterine contractility have not been investigated. The aims of this study were to identify these receptors in the non-pregnant and the late-pregnant rat myometrium and to determine their roles in contractions. We found that the myometrial alpha2-AR subtypes are involved differently in the control of late-pregnant contractions, while they have no influence on the contractions of the non-pregnant myometrium. The myometrial expressions of the alpha2-AR subtypes were determined by RT-PCR and Western blotting techniques. In vitro contractions were stimulated with noradrenaline, and its effect was modified with the selective antagonists BRL 44408 (alpha2A), ARC 239 (alpha2B/C) and spiroxatrine (alpha2C). cAMP production was followed by noradrenaline stimulation in the presence of isobutylmethylxanthine and forskolin, and alterations induced in it by the antagonists were determined with an Enzyme Immunoassay Kit. The most effective antagonist was tested on labour-induced uteri in vitro. All the alpha2-AR subtypes were identified in both non-pregnant and pregnant uteri. Noradrenaline was not able to contract the non-pregnant tissue in the presence of propranolol and doxazosin, while its contracting effect in the pregnant uteri was enhanced by BRL 44408, spiroxatrine and the combination BRL 44408+spiroxatrine. ARC 239 exerted a strong inhibitory effect on noradrenaline-stimulated contractions. The increasing and the decreasing effects of the compounds were confirmed by the changes in the intracellular cAMP levels. The effect of ARC 239 on the labour-induced myometrium was similar to that on the 22-day-pregnant myometrium. The stimulation of alpha2-ARs does not evoke contractions in the non-pregnant uterus. The alpha2A- and alpha2C-ARs mediate decreases, while the alpha2B-AR mediates an increase in the contractions in the 22-day-pregnant myometrium. These differences may offer new

  17. Inhalation of Budesonide/Formoterol Increases Diaphragm Muscle Contractility

    Directory of Open Access Journals (Sweden)

    Chiyohiko Shindoh

    2012-01-01

    Conclusions: BUD/FORM inhalation has an inotropic effect on diaphragm muscle, protects diaphragm muscle deterioration after endotoxin injection, and inhibits NO production. Increments in muscle contractility with BUD/FORM inhalation are induced through a synergistic effect of an anti-inflammatory agent and 02-agonist.

  18. Regional gastrointestinal contractility parameters using the wireless motility capsule

    DEFF Research Database (Denmark)

    Farmer, A D; Wegeberg, A-M L; Brock, B

    2018-01-01

    BACKGROUND: The wireless motility capsule concurrently measures temperature, pH and pressure as it traverses the gastrointestinal tract. AIMS: To describe normative values for motility/contractility parameters across age, gender and testing centres. METHODS: Healthy participants underwent a stand...

  19. Clinical Relationship between Steatocholecystitis and Gallbladder Contractility Measured by Cholescintigraphy

    Directory of Open Access Journals (Sweden)

    Chang Seok Bang

    2015-01-01

    Full Text Available Objective. Contractility of gallbladder is known to be decreased in fatty gallbladder diseases. However, clinical estimation data about this relationship is still lacking. The aim of this study was to investigate the association between steatocholecystitis and contractility of gallbladder. Methods. Patients with cholecystitis (steatocholecystitis versus nonsteatocholecystitis who underwent cholescintigraphy before cholecystectomy were retrospectively evaluated in a single teaching hospital of Korea. The association of steatocholecystitis with contractility of gallbladder, measured by preoperative cholescintigraphy, was assessed by univariable and multivariable analysis. Results. A total of 432 patients were finally enrolled (steatocholecystitis versus nonsteatocholecystitis; 75 versus 357, calculous versus acalculous cholecystitis; 316 versus 116. In the multivariable analysis, age (OR: 0.94, 95% CI: 0.90–0.99, P=0.01 and total serum cholesterol (OR: 1.02, 95% CI: 1.01–1.04, P=0.04 were related to steatocholecystitis in patients with acalculous cholecystitis. Only age (OR: 0.97, 95% CI: 0.94–0.99, P=0.004 was significantly related to steatocholecystitis in patients with calculous cholecystitis. However, ejection fraction of gallbladder reflecting contractility measured by cholescintigraphy was not related to steatocholecystitis irrespective of presence of gallbladder stone in patients with cholecystitis. Conclusion. Ejection fraction of gallbladder measured by cholescintigraphy cannot be used for the detection or confirmation of steatocholecystitis.

  20. Systolic Intrinsic Frequency and Various Measures of Left Ventricle Contractility

    Science.gov (United States)

    Pahlevan, Niema

    2017-11-01

    There has been growing interest during past six decades to introduce new indices for quantifying left ventricular (LV) contractility. We have recently introduced a new method, called intrinsic frequency (IF), for analyzing the dynamics of systemic circulation. IF method models LV and arterial network as an object rotating around an origin where the angular velocity of the rotation during systole (when LV and arterial network are coupled) and diastole (when arterial network is decoupled) are intrinsic frequencies, ω1 and ω2 respectively. ω1 and ω2 can be extracted from a carotid pulse waveform using IF method. In this study, Huntington Medical Research Institutes heart study data have been used to compare ω1 with various measures of LV contractility such as ejection fraction, mean velocity of circumferential fiber shortening, LV end-systolic meridional wall stress, and maximal LV power corrected for end-diastolic volume. Here, LV contractility indices were computed noninvasively from cardiac MRI and tonometry data. The results indicate that ω1 can be used as a surrogate of LV contractility. This is clinically significant since ω1 can be accurately obtained by a standard iPhone camera.

  1. Tension cost correlates with mechanical and biochemical parameters in different myocardial contractility conditions

    Directory of Open Access Journals (Sweden)

    Cleci M. Moreira

    2012-01-01

    Full Text Available OBJECTIVES: Tension cost, the ratio of myosin ATPase activity to tension, reflects the economy of tension development in the myocardium. To evaluate the mechanical advantage represented by the tension cost, we studied papillary muscle contractility and the activity of myosin ATPase in the left ventricles in normal and pathophysiological conditions. METHODS: Experimental protocols were performed using rat left ventricles from: (1 streptozotocin-induced diabetic and control Wistar rats; (2 N-nitro-L-arginine methyl ester (L-NAME hypertensive and untreated Wistar rats; (3 deoxycorticosterone acetate (DOCA salt-treated, nephrectomized and salt- and DOCA-treated rats; (4 spontaneous hypertensive rats (SHR and Wistar Kyoto (WKY rats; (5 rats with myocardial infarction and shamoperated rats. The isometric force, tetanic tension, and the activity of myosin ATPase were measured. RESULTS: The results obtained from infarcted, diabetic, and deoxycorticosterone acetate-salt-treated rats showed reductions in twitch and tetanic tension compared to the control and sham-operated groups. Twitch and tetanic tension increased in the N-nitro-L-arginine methyl ester-treated rats compared with the Wistar rats. Myosin ATPase activity was depressed in the infarcted, diabetic, and deoxycorticosterone acetate salt-treated rats compared with control and sham-operated rats and was increased in N-nitro-L-arginine methyl ester-treated rats. These parameters did not differ between SHR and WKY rats. In the studied conditions (e.g., post-myocardial infarction, deoxycorticosterone acetate salt-induced hypertension, chronic N-nitro-L-arginine methyl ester treatment, and streptozotocin-induced diabetes, a positive correlation between force or plateau tetanic tension and myosin ATPase activity was observed. CONCLUSION: Our results suggest that the myocardium adapts to force generation by increasing or reducing the tension cost to maintain myocardial contractility with a better

  2. Is Tumor Size Really Important for Prediction of Lymphatic Dissemination in Grade 1 Endometrial Carcinoma With Superficial Myometrial Invasion?

    Science.gov (United States)

    Oz, Murat; Korkmaz, Vakkas; Meydanli, Mehmet Mutlu; Sari, Mustafa Erkan; Cuylan, Zeliha Firat; Gungor, Tayfun

    2017-09-01

    Selection of patients with endometrioid endometrial cancer (EEC), in whom systematic lymph node dissection (LND) is indicated, is an important part of management to maintain optimal oncological outcomes, while avoiding unnecessary morbidities. According to the current approach, LND is recommended for the patients with International Federation of Gynecology and Obstetrics (FIGO) grade 1 to 2 tumors and a primary tumor diameter (PTD) greater than 2 cm, even with myometrial invasion (MMI) of less than 50%. We aimed to determine incidence of LN metastasis in this particular group of patients with grade 1 tumors, superficial MMI, and a PTD greater than 2 cm. This study only focused on women with FIGO grade 1 EEC having less than 50% MMI. Therefore, women with grade 2 or 3 tumors were excluded, as well as patients with 50% or greater MMI. We also excluded women with macroscopic extrauterine disease, as well as patients with cervical stromal involvement. Patients were divided into subgroups with regard to PTD; group 1 was composed of patients with PTD of 20 mm or less, whereas group 2 was composed of patients with PTD greater than 20 mm. All clinical and pathological variables were compared between the groups. Final pathology reports of 484 women with EEC who underwent surgical staging were analyzed. Among these women, there were 123 women in group 1 (PTD ≤ 20 mm) and 120 women in group 2 (PTD > 20 mm), with FIGO grade 1 tumors and superficial MMI. The median number of total LNs removed was 54 (range, 20-151). There were no women with pelvic and/or para-aortic LN metastasis in group 2, as well as in group 1. Our results suggest that lymphadenectomy may be omitted in women with FIGO grade 1 EEC having superficial MMI regardless of PTD. Deferral of systematic LND in this subgroup of patients may lead to reductions in costs and surgical morbidity.

  3. Extra and intracellular calcium signaling pathway(s) differentially regulate histamine-induced myometrial contractions during early and mid-pregnancy stages in buffaloes (Bubalus bubalis).

    Science.gov (United States)

    Sharma, Abhishek; Nakade, Udayraj P; Choudhury, Soumen; Yadav, Rajkumar Singh; Garg, Satish Kumar

    2017-04-01

    This study examines the differential role of calcium signaling pathway(s) in histamine-induced uterotonic action during early and mid-pregnancy stages in buffaloes. Compared to mid pregnancy, tonic contraction, amplitude and mean-integral tension were significantly increased by histamine to produce myometrial contraction during early pregnancy with small effects on phasic contraction and frequency. Although uterotonic action of histamine during both stages of pregnancy is sensitive to nifedipine (a L-type Ca 2+ channels blocker) and NNC55-0396 (T-type Ca 2+ channels blocker), the role of extracellular calcium seems to be more significant during mid-pregnancy as in this stage histamine produced only 9.38±0.96% contraction in Ca 2+ free-RLS compared to 21.60±1.45% in uteri of early pregnancy stage. Intracellular calcium plays major role in histamine-induced myometrial contraction during early pregnancy as compared to mid pregnancy, as in the presence of cyclopiazonic acid (CPA) Ca 2+ -free RLS, histamine produced significantly higher contraction in myometrial strips of early-pregancy in comparison to mid-pregnancy (10.59±1.58% and 3.13±0.46%, respectively). In the presence of U-73122, the DRC of histamine was significantly shifted towards right with decrease in maximal effect (E max ) only in early pregnancy suggesting the predominant role of phospholipase-C (PL-C) in this stage of pregnancy. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Adjustment of serum HE4 to reduced glomerular filtration and its use in biomarker-based prediction of deep myometrial invasion in endometrial cancer

    DEFF Research Database (Denmark)

    Chovanec, Josef; Serlingerova, Iveta; Greplova, Kristina

    2017-01-01

    Background: We investigated the efficacy of circulating biomarkers together with histological grade and age to predict deep myometrial invasion (dMI) in endometrial cancer patients. Methods: HE4ren was developed adjusting HE4 serum levels towards decreased glomerular filtration rate as quantified...... based on single-institution data from 120 EC patients and validated against multicentric data from 379 EC patients. Results: In non-cancer individuals, serum HE4 levels increase log-linearly with reduced glomerular filtration of eGFR = 90 ml/min/1.73 m2. HE4ren, adjusting HE4 serum levels to decreased e...

  5. Spontaneous uterine rupture

    African Journals Online (AJOL)

    ABSTRACT. Rupture of a gravid uterus is a surgical emergency. Predisposing factors include a scarred uterus. Spontaneous rupture of an unscarred uterus during pregnancy is a rare occurrence. We hereby present the case of a spontaneous complete uterine rupture at a gestational age of 34 weeks in a 35 year old patient ...

  6. Spontaneous intracranial hypotension.

    LENUS (Irish Health Repository)

    Fullam, L

    2012-01-31

    INTRODUCTION: Spontaneous\\/primary intracranial hypotension is characterised by orthostatic headache and is associated with characteristic magnetic resonance imaging findings. CASE REPORT: We present a case report of a patient with typical symptoms and classical radiological images. DISCUSSION: Spontaneous intracranial hypotension is an under-recognised cause of headache and can be diagnosed by history of typical orthostatic headache and findings on MRI brain.

  7. Impact of Severe Thermal Injury on Cardiac Contractility and Metabolism

    Directory of Open Access Journals (Sweden)

    M. A. Goldzon

    2011-01-01

    Full Text Available Objective: to experimentally study cardiac functional and metabolic disturbances in the acute period of severe thermal injury. Material and methods. Experiments were carried out on 25 outbred male albino rats anesthesized with Nembutal (50 mg/kg intraperitoneally. Five-mm-thick copper plates heated up to 60°C were used to simulate thermal injury. Skin contact with the thermal agent lasted 15 seconds. Myocardial contractility and metabolism were examined using the specimen of the isolated isovolumically contracted heart. Results. Severe thermal injury was found to induce acute heart failure caused by cardiac bioenergy impairment, hypoxia, metabolic acidosis, and cardiomyocyte membrane destruction. Key words: thermal injury, cardiac contractility and metabolism.

  8. Disordered Actomyosin Is Sufficient to Promote Cooperative and Telescopic Contractility

    Science.gov (United States)

    Murrell, Michael; Linsmeier, Ian; Banerjee, Shiladitya; Kim, Tae Yoon; Jung, Wonyeong; Oakes, Patrick

    While the molecular interactions between myosin motors and F-actin are well known, the relationship between F-actin organization and myosin-mediated force generation remains poorly understood. Here, we explore the accumulation of myosin-induced stresses within a 2D biomimetic model of the actomyosin cortex, where myosin activity is controlled spatially and temporally using light. By controlling the geometry and the duration of myosin activation, we show that contraction of disordered actomyosin is highly cooperative, telescopic with the activation area and generates a pattern of mechanical stresses consistent with those observed in contractile cells. We quantitatively reproduce these properties using an in vitro isotropic model of the actomyosin cytoskeleton, and explore the physical origins of telescopic contractility in disordered networks using agent-based simulations. NSF CMMI-1525316.

  9. Effect of Aloe Barbadensis on Rat's Uterine Contractility | Iranloye ...

    African Journals Online (AJOL)

    The present study was undertaken to investigate the effect of the aqueous extract of Aloe barbadensis on the contractility of the uterine stip of a rat. Aqueous extract at final bath concentrations (FBC)1x10-4 mg/ml to 3x101 mg/ml produced a progressive increase in frequency of contraction of the uterine strip. The force of ...

  10. Multicellular contractility contributes to the emergence of mesothelioma nodules

    Science.gov (United States)

    Czirok, Andras

    Malignant pleural mesothelioma (MPM) nodules arise from the mesothelial lining of the pleural cavity by a poorly understood mechanism. We demonstrate that macroscopic multicellular aggregates, reminiscent of the MPM nodules found in patients, develop when MPM cell lines are cultured at high cell densities for several weeks. Surprisingly, the nodule-like aggregates do not arise by excessive local cell proliferation, but by myosin II-driven cell contractility. Contractile nodules contain prominent actin cables that can span several cells. Several features of the in vitro MPM nodule development can be explained by a computational model that assumes uniform and steady intercellular contractile forces within a monolayer of cells, and a mechanical load-dependent lifetime of cell-cell contacts. The model behaves as a self-tensioned Maxwell fluid and exhibits an instability that leads to pattern formation. Altogether, our findings suggest that inhibition of the actomyosin system may provide a hitherto not utilized therapeutic approach to affect MPM growth. NIH R01-GM102801.

  11. TREK-1 Channel Expression in Smooth Muscle as a Target for Regulating Murine Intestinal Contractility: Therapeutic Implications for Motility Disorders

    Directory of Open Access Journals (Sweden)

    Ruolin Ma

    2018-03-01

    Full Text Available Gastrointestinal (GI motility disorders such as irritable bowel syndrome (IBS can occur when coordinated smooth muscle contractility is disrupted. Potassium (K+ channels regulate GI smooth muscle tone and are key to GI tract relaxation, but their molecular and functional phenotypes are poorly described. Here we define the expression and functional roles of mechano-gated K2P channels in mouse ileum and colon. Expression and distribution of the K2P channel family were investigated using quantitative RT-PCR (qPCR, immunohistochemistry and confocal microscopy. The contribution of mechano-gated K2P channels to mouse intestinal muscle tension was studied pharmacologically using organ bath. Multiple K2P gene transcripts were detected in mouse ileum and colon whole tissue preparations. Immunohistochemistry confirmed TREK-1 expression was smooth muscle specific in both ileum and colon, whereas TREK-2 and TRAAK channels were detected in enteric neurons but not smooth muscle. In organ bath, mechano-gated K2P channel activators (Riluzole, BL-1249, flufenamic acid, and cinnamyl 1-3,4-dihydroxy-alpha-cyanocinnamate induced relaxation of KCl and CCh pre-contracted ileum and colon tissues and reduced the amplitude of spontaneous contractions. These data reveal the specific expression of mechano-gated K2P channels in mouse ileum and colon tissues and highlight TREK-1, a smooth muscle specific K2P channel in GI tract, as a potential therapeutic target for combating motility pathologies arising from hyper-contractility.

  12. The radiological myometrial appearance after cesarean section: is it associated with postpartum complications and subsequent delivery outcome?

    Science.gov (United States)

    Bogot, Naama R; Rottenstreich, Misagv; Nabulsi, Rinad M; Turner, Yonatan; Farkash, Rivka; Samueloff, Arnon; Grisaru-Granovsky, Sorina

    2017-11-28

    To evaluate whether the characteristics of the radiological uterine myometrial discontinuity (RMD) is associated with maternal-neonatal outcomes and post-cesarean section (CS) complications. A secondary aim was to describe the evolution of the CT uterine surgical incision and the related outcome of a subsequent trial of labor after cesarean (TOLAC). Single center retrospective cohort study of CT scans was performed within 6 weeks from cesarean delivery. Demographic characteristics of patients were recorded (age, intrapartum fever, CS data, and hospital stay length). Abdominopelvic CT scans were performed using a multidetector CT (16 or 256 slice) with intravenous contrast material. CT analysis was performed by two radiologists in consensus. The RMD seen as low attenuation gap in expected incision site was assessed for: visualization, thickness, and presence of gas. Logistic regression analysis was fitted to assess the relationship of the delivery-CT time interval with the presence of RMD and gas. Of a total of 75,791 births during the study period there were 8775 CS (11.6%). The study group consisted of 101 CTs in 84 woman after CS. RMD defined in 73 (72.2%) of all CT exams; the mean RMD thickness was 7 mm ± 3.9, "RMD gas" observed in 15 (17.9%) of CT exams. RMD thickness or gas presence were strongly associated with a CS-1st CT exam time interval of less than 7 days, OR 5.8 [CI 1.5-22.6], p = 0.010, but not with maternal, delivery, or neonatal characteristics. A subsequent successful vaginal birth was achieved in 75% of the patients with no uterine rupture, regardless of the RMD gas presence. RMD gas visualization on CT is not associated with febrile morbidity, cesarean characteristics, and subsequent TOLAC results. RMD gas is a normal post-operative finding and should not lead to changes in the postpartum delivery complication management or recommendations for the future mode of delivery.

  13. Enhanced Expression of Contractile-Associated Proteins and Ion Channels in Preterm Delivery Model Mice With Chronic Odontogenic Porphyromonas Gingivalis Infection.

    Science.gov (United States)

    Miyoshi, Hiroshi; Konishi, Haruhisa; Teraoka, Yuko; Urabe, Satoshi; Furusho, Hisako; Miyauchi, Mutsumi; Takata, Takashi; Kudo, Yoshiki

    2016-07-01

    Inflammation and infection have been reported to induce preterm delivery. We have studied the relationship between inflammation and various ion channels, including the L-type Ca(2+) channel and P2X7 receptor, during acute inflammation of the pregnant rat uterus induced by lipopolysaccharides. Recently, we found that mice with odontogenic Porphyromonas gingivalis (P.g, an important odontogenic pathogen) infection delivered at day 18.3 of gestation (vs. day 20.5 in normal mice). The purpose of this study was to investigate the expression of myometrial contractile-associated proteins inducing contractions and confirm that these mice are useful as a model for preterm delivery induced by chronic inflammation. We examined the expression of the oxytocin receptor, connexin 43, prostaglandin F receptors, L-type Ca(2+) channel, and P2X7 receptor in the myometrium at day 18 of gestation by real-time PCR and western blot analyses. We also measured TNF-α and IL-1β levels in the blood serum, placenta, fetal membrane and myometrium on the same day. mRNA expression of the oxytocin receptor, connexin 43, prostaglandin F receptors, L-type Ca(2+) channel, and P2X7 receptor was elevated by 5.4, 3.2, 2.4, 2.5, and 1.7 fold, respectively, in the P.g-infected mice. Protein levels of the oxytocin receptor and connexin 43 also increased. Serum levels of TNF-α and IL-1β were elevated, showing that systemic inflammation continued during pregnancy. IL-1β levels in the placenta and fetal membrane also increased, suggesting inflammatory reactions were induced. Thus, mice with odontogenic infection may be useful as a model of chronic inflammation-induced preterm delivery. © The Author(s) 2015.

  14. MR diffusion imaging for preoperative staging of myometrial invasion in patients with endometrial cancer: a systematic review and meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Andreano, Anita; Rebora, Paola; Valsecchi, Maria Grazia; Galimberti, Stefania [University of Milano-Bicocca, Center of Biostatistics for Clinical Epidemiology, Department of Health Sciences, Monza, MB (Italy); Rechichi, Gilda [S. Gerardo Hospital, Department of Radiology, Monza, MB (Italy); Sironi, Sandro [University of Milano-Bicocca, Center of Biostatistics for Clinical Epidemiology, Department of Health Sciences, Monza, MB (Italy); S. Gerardo Hospital, Department of Radiology, Monza, MB (Italy)

    2014-06-15

    To compare the diagnostic accuracy of dynamic contrast-enhanced (DCE) and diffusion-weighted (DW) MR imaging in detecting deep myometrial invasion in endometrial cancer, using surgical-pathological staging as reference standard. After searching a wide range of electronic databases and screening titles/abstracts, we obtained full papers for potentially eligible studies and evaluated according to predefined inclusion criteria. Quality assessment was conducted by adapting the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) checklist. From each study, we extracted information on diagnostic performance of DW and DCE sequences. After exploring heterogeneity, we adopted a bivariate generalized linear mixed model to compare the effect of the two MR sequences jointly on sensitivity and specificity. Nine studies (442 patients) were considered. Significant evidence of heterogeneity was found only for specificity, both in DW and DCE imaging (I {sup 2} = 70.8 % and 70.6 %). Pooled sensitivity of DW and DCE was 0.86 and specificity did not significantly differ (p = 0.16) between the two sequences (DW = 0.86 and DCE = 0.82). No difference was found between 3-T and 1.5-T MR. There was no evidence of publication bias. MR diagnostic accuracy in presurgical detection of deep myometrial infiltration in endometrial cancer is high. DCE and DW imaging do not differ in sensitivity and specificity. (orig.)

  15. Nitrate supplementation enhances the contractile properties of human skeletal muscle.

    Science.gov (United States)

    Haider, Georg; Folland, Jonathan P

    2014-12-01

    Dietary nitrate supplementation positively affects cardiovascular function at rest and energy metabolism during exercise in humans and has recently also been reported to markedly enhance the in vitro contractile properties of mouse fast-twitch muscle. The aim of this study was to investigate the effects of short-term nitrate supplementation on the in vivo contractile properties of the skeletal muscle and voluntary muscle function of humans. In a double-blind, randomized, crossover design, 19 healthy untrained men (21 ± 3 yr) ingested a nitrate-rich concentrated beetroot juice (NIT; nitrate dosage, approximately 9.7 mmol·d) and a placebo (PLA) for seven consecutive days. After the last supplementation dose, force was recorded while participants completed a series of voluntary and involuntary (electrically evoked) unilateral isometric contractions of the knee extensors. NIT enhanced the peak force response to low-frequency electrical stimulation, as follows: maximal twitch (NIT, 149 ± 41 N, vs PLA, 138 ± 37 N; P = 0.008; effect size, r (ES) = 0.56) and submaximal 1- to 20-Hz contractions (5%-10%, ES = 0.53-0.63). Whereas explosive (rising phase) force production during the first 50 ms of evoked maximal twitch and octet contractions (eight electrical impulses at 300 Hz) was also 3%-15% greater after NIT compared with that after PLA (P = 0.023-0.048, ES = 0.52-0.59), explosive voluntary force remained similar (P = 0.510, ES = 0.16). Maximum voluntary force was also unchanged after NIT (P = 0.539, ES = 0.15). These results indicate that 7 d of dietary nitrate supplementation enhanced the in vivo contractile properties of the human skeletal muscle. Specifically, nitrate supplementation improved excitation-contraction coupling at low frequencies of stimulation and enhanced evoked explosive force production but did not affect maximum or explosive voluntary force production in untrained individuals.

  16. Myometrial invasion and overall staging of endometrial carcinoma: assessment using fusion of T2-weighted magnetic resonance imaging and diffusion-weighted magnetic resonance imaging

    Directory of Open Access Journals (Sweden)

    Guo Y

    2017-12-01

    Full Text Available Yu Guo,1,2 Ping Wang,2 Penghui Wang,2 Wei Gao,1 Fenge Li,3 Xueling Yang,1 Hongyan Ni,2 Wen Shen,2 Zhi Guo1 1Department of Interventional Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin, 2Department of Radiology, Tianjin First Center Hospital, The First Central Clinical College of Tianjin Medical University, Tianjin, 3Department of Gynecology, Tianjin First Center Hospital, Tianjin, People’s Republic of China Background: The age of onset of endometrial carcinoma has been decreasing in recent years. In endometrial carcinoma, it is important to accurately assess invasion depth and preoperative staging. Fusion of T2-weighted magnetic resonance imaging (T2WI and diffusion-weighted magnetic resonance imaging (DWI may contribute to the improvement of anatomical localization of lesions.Materials and methods: In our study, a total of 58 endometrial carcinoma cases were included. Based on the revised 2009 International Federation of Gynecology and Obstetrics staging system, a fusion of T2WI and DWI was utilized for the evaluation of invasion depth and determination of the overall stage. Postoperative pathologic assessment was considered as the reference standard. The consistency of T2WI image staging and pathologic staging, and the consistency of fused T2WI and DWI and pathologic staging were all analyzed using Kappa statistics.Results: Compared with the T2WI group, a significantly higher diagnostic accuracy was observed for myometrial invasion with fusion of T2WI and DWI (77.6% for T2WI; 94.8% for T2WI-DWI. For the identification of deep invasion, we calculated values for diagnostic sensitivity (69.2% for T2WI; 92.3% for T2WI-DWI, specificity (80% for T2WI; 95.6% for T2WI-DWI, positive predictive value (50% for T2WI; 85.7% for T2WI-DWI, and negative predictive value (90% for

  17. Opioid mediated activity and expression of mu and delta opioid receptors in isolated human term non-labouring myometrium.

    LENUS (Irish Health Repository)

    Fanning, Rebecca A

    2013-01-05

    The existence of opioid receptors in mammalian myometrial tissue is now widely accepted. Previously enkephalin degrading enzymes have been shown to be elevated in pregnant rat uterus and a met-enkephalin analogue has been shown to alter spontaneous contractility of rat myometrium. Here we have undertaken studies to determine the effects of met-enkephalin on in vitro human myometrial contractility and investigate the expression of opioid receptors in pregnant myometrium. Myometrial biopsies were taken from women undergoing elective caesarean delivery at term. Organ bath experiments were used to investigate the effect of the met-enkephalin analogue [d-Ala 2, d-met 5] enkephalin (DAMEA) on spontaneous contractility. A confocal immunofluorescent technique and real time PCR were used to determine the expression of protein and mRNA, respectively for two opioid receptor subtypes, mu and delta. DAMEA had a concentration dependent inhibitory effect on contractile activity (1 × 10(-7)M-1 × 10(-4)M; 54% reduction in contractile activity, P<0.001 at 1 × 10(-4)M concentration). Mu and delta opioid receptor protein sub-types and their respective mRNA were identified in all tissues sampled. This is the first report of opioid receptor expression and of an opioid mediated uterorelaxant action in term human non-labouring myometrium in vitro.

  18. Spontaneous activity in peripheral diaphragmatic lymphatic loops.

    Science.gov (United States)

    Moriondo, Andrea; Solari, Eleonora; Marcozzi, Cristiana; Negrini, Daniela

    2013-10-01

    The spontaneous contractility of FITC-dextran-filled lymphatics at the periphery of the pleural diaphragm was documented for the first time "in vivo" in anesthetized Wistar rats. We found that lymphatic segments could be divided into four phenotypes: 1) active, displaying rhythmic spontaneous contractions (51.8% of 197 analyzed sites); 2) stretch-activated, whose contraction was triggered by passive distension of the vessel lumen (4.1%); 3) passive, which displayed a completely passive distension (4.5%); and 4) inert, whose diameter never changed over time (39.6%). Smooth muscle actin was detected by immunofluorescence and confocal microscopy in the vessel walls of active but also of inert sites, albeit with a very different structure within the vessel wall. Indeed, while in active segments, actin was arranged in a dense mesh completely surrounding the lumen, in inert segments actin decorated the vessels wall in sparse longitudinal strips. When located nearby along the same lymphatic loop, active, stretch-activated, and passive sites were always recruited in temporal sequence starting from the active contraction. The time delay was ∼0.35 s between active and stretch-activated and 0.54 s between stretch-activated and passive segments, promoting a uniform lymph flux of ∼150/200 pl/min. We conclude that, unlike more central diaphragmatic lymphatic vessels, loops located at the extreme diaphragmatic periphery do require an intrinsic pumping mechanism to propel lymph centripetally, and that such an active lymph propulsion is attained by means of a complex interplay among sites whose properties differ but are indeed able to organize lymph flux in an ordered fashion.

  19. Resolving the role of actoymyosin contractility in cell microrheology.

    Directory of Open Access Journals (Sweden)

    Christopher M Hale

    2009-09-01

    Full Text Available Einstein's original description of Brownian motion established a direct relationship between thermally-excited random forces and the transport properties of a submicron particle in a viscous liquid. Recent work based on reconstituted actin filament networks suggests that nonthermal forces driven by the motor protein myosin II can induce large non-equilibrium fluctuations that dominate the motion of particles in cytoskeletal networks. Here, using high-resolution particle tracking, we find that thermal forces, not myosin-induced fluctuating forces, drive the motion of submicron particles embedded in the cytoskeleton of living cells. These results resolve the roles of myosin II and contractile actomyosin structures in the motion of nanoparticles lodged in the cytoplasm, reveal the biphasic mechanical architecture of adherent cells-stiff contractile stress fibers interdigitating in a network at the cell cortex and a soft actin meshwork in the body of the cell, validate the method of particle tracking-microrheology, and reconcile seemingly disparate atomic force microscopy (AFM and particle-tracking microrheology measurements of living cells.

  20. Lidocaine decreases the xylazine-evoked contractility in pregnant cows.

    Science.gov (United States)

    Piccinno, M; Rizzo, A; Mutinati, M; D'Onghia, G; Sciorsci, R L

    2016-08-01

    The objective of this in vitro study was to evaluate and compare the effects of xylazine on basal uterine contractility of bovine pregnant uterine strips and that of lidocaine on xylazine-sensitized bovine pregnant uterine strips, at different stages of pregnancy. Basal contractility was evaluated in an isolated organ bath and the functionality of the strips throughout the experiment was evaluated using a dose of carbachol (10(-5)M). Uterine motility, expressed with amplitude, frequency of contractions as well as the area under the curve, was recorded in different stages of pregnancy and data were collected at 15-min intervals (5-min before and 5-min after xylazine administration and 5-min after lidocaine addition on the plateau contraction induced by xylazine). Uterine motility increased in all the stages of pregnancy after xylazine addition and gradually decreased after treatment with lidocaine. These data suggest that lidocaine might decrease the tonic effect induced by xylazine on bovine pregnant uteri. Copyright © 2016. Published by Elsevier Ltd.

  1. Fiber plucking: large emergent contractility in stiff biopolymer networks

    Science.gov (United States)

    Ronceray, Pierre; Broedersz, Chase; Lenz, Martin

    The mechanical properties of the cell depend crucially on the tension of its cytoskeleton. Contractile stresses in this fiber network originate from the forces exerted by active motor proteins. Importantly, experimentally observed cell-scale stresses are much larger than would be expected from linear elastic transmission of the molecular forces. We have recently proposed a mechanism for this nonlinear stress amplification, involving extended filament buckling in the network. We propose here an alternate mechanism: when active forces are exerted transversely on a filament, they induce a nonlinear tension in the plucked fiber. The resulting contractile response in the far-field can overwhelm dramatically the linear stress prediction. Importantly, such a plucking force amplification relies on the surrounding network to be stiff and only moderately stressed. These conditions compete with those required to observe amplification due to fiber buckling. Fiber networks thus provide several distinct pathways for living systems to amplify their molecular forces. Their relative importance in biological relevant situations could be assessed using experimentally testable scaling laws.

  2. Pelvic floor muscle contractility: digital assessment vs transperineal ultrasound.

    Science.gov (United States)

    van Delft, K; Thakar, R; Sultan, A H

    2015-02-01

    A significant reduction in hiatal area and anteroposterior diameter can be induced by pelvic floor muscle contraction, and this has been demonstrated using three-dimensional/four-dimensional (3D/4D) transperineal ultrasound (TPS) in a small group of women. Our objective was to correlate pelvic floor muscle contractility using digital assessment with the change in TPS hiatus measurements during maximum pelvic floor muscle contraction. Nulliparous pregnant women were recruited from the antenatal clinic. Pelvic floor muscle contractility was assessed by digital palpation using the validated Modified Oxford Scale (MOS). Subsequently, women underwent 3D/4D TPS. Measurements of the hiatal area and anteroposterior diameter were taken from the rendered ultrasound images at rest and at maximum contraction, and differences in measurements were expressed as percentages. Spearman's rank (ρ) was used to assess the correlation. Four hundred and fifty-nine assessments were performed, of which 268 were from women at around 36 weeks' gestation, and 191 were from women following delivery at 3 months postpartum. The overall correlation between MOS and TPS was found to be ρ = 0.47 for hiatal area (P biofeedback when training patients in pelvic floor muscle exercises. As TPS is non-intrusive, it may be the method of choice for some women. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

  3. Effect of serotonin on small intestinal contractility in healthy volunteers

    DEFF Research Database (Denmark)

    Hansen, M.B.; Arif, F.; Gregersen, H.

    2008-01-01

    The physiological significance of serotonin released into the intestinal lumen for the regulation of motility is unknown in humans. The aim of this study was to evaluate the effect of serotonin infused into the lumen of the gastric antrum, duodenum or the jejunum, on antro-duodeno-jejunal contrac......The physiological significance of serotonin released into the intestinal lumen for the regulation of motility is unknown in humans. The aim of this study was to evaluate the effect of serotonin infused into the lumen of the gastric antrum, duodenum or the jejunum, on antro......-duodeno-jejunal contractility in healthy human volunteers. Manometric recordings were obtained and the effects of either a standard meal, continuous intravenous infusion of serotonin (20 nmol/kg/min) or intraluminal bolus infusions of graded doses of serotonin (2.5, 25 or 250 nmol) were compared. In addition, platelet......-depleted plasma levels of serotonin, blood pressure, heart rate and electrocardiogram were evaluated. All subjects showed similar results. Intravenous serotonin increased migrating motor complex phase In frequency 3-fold and migrating velocity 2-fold. Intraluminal infusion of serotonin did not change contractile...

  4. Human Engineered Heart Tissue: Analysis of Contractile Force.

    Science.gov (United States)

    Mannhardt, Ingra; Breckwoldt, Kaja; Letuffe-Brenière, David; Schaaf, Sebastian; Schulz, Herbert; Neuber, Christiane; Benzin, Anika; Werner, Tessa; Eder, Alexandra; Schulze, Thomas; Klampe, Birgit; Christ, Torsten; Hirt, Marc N; Huebner, Norbert; Moretti, Alessandra; Eschenhagen, Thomas; Hansen, Arne

    2016-07-12

    Analyzing contractile force, the most important and best understood function of cardiomyocytes in vivo is not established in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). This study describes the generation of 3D, strip-format, force-generating engineered heart tissues (EHT) from hiPSC-CM and their physiological and pharmacological properties. CM were differentiated from hiPSC by a growth factor-based three-stage protocol. EHTs were generated and analyzed histologically and functionally. HiPSC-CM in EHTs showed well-developed sarcomeric organization and alignment, and frequent mitochondria. Systematic contractility analysis (26 concentration-response curves) reveals that EHTs replicated canonical response to physiological and pharmacological regulators of inotropy, membrane- and calcium-clock mediators of pacemaking, modulators of ion-channel currents, and proarrhythmic compounds with unprecedented precision. The analysis demonstrates a high degree of similarity between hiPSC-CM in EHT format and native human heart tissue, indicating that human EHTs are useful for preclinical drug testing and disease modeling. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  5. Spontaneous Atraumatic Mediastinal Hemorrhage

    Directory of Open Access Journals (Sweden)

    Morkos Iskander BSc, BMBS, MRCS, PGCertMedEd

    2013-04-01

    Full Text Available Spontaneous atraumatic mediastinal hematomas are rare. We present a case of a previously fit and well middle-aged lady who presented with acute breathlessness and an increasing neck swelling and spontaneous neck bruising. On plain chest radiograph, widening of the mediastinum was noted. The bruising was later confirmed to be secondary to mediastinal hematoma. This life-threatening diagnostic conundrum was managed conservatively with a multidisciplinary team approach involving upper gastrointestinal and thoracic surgeons, gastroenterologists, radiologists, intensivists, and hematologists along with a variety of diagnostic modalities. A review of literature is also presented to help surgeons manage such challenging and complicated cases.

  6. Proinflammatory Cytokines Are Soluble Mediators Linked with Ventricular Arrhythmias and Contractile Dysfunction in a Rat Model of Metabolic Syndrome

    Science.gov (United States)

    Fernández-Sada, Evaristo; Silva-Platas, Christian; García, Noemí; Rodríguez-Rodríguez, César; De la Peña, Erasmo; Bernal-Ramírez, Judith

    2017-01-01

    Metabolic syndrome (MS) increases cardiovascular risk and is associated with cardiac dysfunction and arrhythmias, although the precise mechanisms are still under study. Chronic inflammation in MS has emerged as a possible cause of adverse cardiac events. Male Wistar rats fed with 30% sucrose in drinking water and standard chow for 25–27 weeks were compared to a control group. The MS group showed increased weight, visceral fat, blood pressure, and serum triglycerides. The most important increases in serum cytokines included IL-1β (7-fold), TNF-α (84%), IL-6 (41%), and leptin (2-fold), the latter also showing increased gene expression in heart tissue (35-fold). Heart function ex vivo in MS group showed a decreased mechanical performance response to isoproterenol challenge (ISO). Importantly, MS hearts under ISO showed nearly twofold the incidence of ventricular fibrillation. Healthy rat cardiomyocytes exposed to MS group serum displayed impaired contractile function and Ca2+ handling during ISO treatment, showing slightly decreased cell shortening and Ca2+ transient amplitude (23%), slower cytosolic calcium removal (17%), and more frequent spontaneous Ca2+ release events (7.5-fold). As spontaneous Ca2+ releases provide a substrate for ventricular arrhythmias, our study highlights the possible role of serum proinflammatory mediators in the development of arrhythmic events during MS. PMID:29201273

  7. Crosstalk between monocytes and myometrial smooth muscle in culture generates synergistic pro-inflammatory cytokine production and enhances myocyte contraction, with effects opposed by progesterone

    Science.gov (United States)

    Rajagopal, S.P.; Hutchinson, J.L.; Dorward, D.A.; Rossi, A.G.; Norman, J.E.

    2015-01-01

    Both term and preterm parturition are characterized by an influx of macrophages and neutrophils into the myometrium and cervix, with co-incident increased peripheral blood monocyte activation. Infection and inflammation are strongly implicated in the pathology of preterm labour (PTL), with progesterone considered a promising candidate for its prevention or treatment. In this study, we investigated the effect of monocytes on myometrial smooth muscle cell inflammatory cytokine production both alone and in response to LPS, a TLR4 agonist used to trigger PTL in vivo. We also investigated the effect of monocytes on myocyte contraction. Monocytes, isolated from peripheral blood samples from term pregnant women, were cultured alone, or co-cultured with PHM1-41 myometrial smooth muscle cells, for 24 h. In a third set of experiments, PHM1-41 myocytes were cultured for 24 h in isolation. Cytokine secretion was determined by ELISA or multiplex assays. Co-culture of monocytes and myocytes led to synergistic secretion of pro-inflammatory cytokines and chemokines including IL-6, IL-8 and MCP-1, with the secretion being further enhanced by LPS (100 ng/ml). The synergistic secretion of IL-6 and IL-8 from co-cultures was mediated in part by direct cell–cell contact, and by TNF. Conditioned media from co-cultures stimulated contraction of PHM1-41 myocytes, and the effect was inhibited by progesterone. Both progesterone and IL-10 inhibited LPS-stimulated IL-6 and IL-8 secretion from co-cultures, while progesterone also inhibited chemokine secretion. These data suggest that monocytes infiltrating the myometrium at labour participate in crosstalk that potentiates pro-inflammatory cytokine secretion, an effect that is enhanced by LPS, and can augment myocyte contraction. These effects are all partially inhibited by progesterone. PMID:26002969

  8. Spontaneous Appendicocutaneous Fistula I

    African Journals Online (AJOL)

    M T0k0de* MB, BS and. Dr 0. A. AWOj0bi+ FMCS (Nig). ABSTRACT. Ruptured appendicitis is not a common cause of spontaneous enterocutaneous fistula. A case of ruptured retrocaecal appendicitis presenting as an enterocutaneous fistula in a Nigerian woman is presented. The literature on this disorder is also reviewed.

  9. [Spontaneous bacterial peritonitis].

    Science.gov (United States)

    Strauss, Edna; Caly, Wanda Regina

    2003-01-01

    Spontaneous bacterial peritonitis occurs in 30% of patients with ascites due to cirrhosis leading to high morbidity and mortality rates. The pathogenesis of spontaneous bacterial peritonitis is related to altered host defenses observed in end-stage liver disease, overgrowth of microorganisms, and bacterial translocation from the intestinal lumen to mesenteric lymph nodes. Clinical manifestations vary from severe to slight or absent, demanding analysis of the ascitic fluid. The diagnosis is confirmed by a number of neutrophils over 250/mm3 associated or not to bacterial growth in culture of an ascites sample. Enterobacteriae prevail and Escherichia coli has been the most frequent bacterium reported. Mortality rates decreased markedly in the last two decades due to early diagnosis and prompt antibiotic treatment. Third generation intravenous cephalosporins are effective in 70% to 95% of the cases. Recurrence of spontaneous bacterial peritonitis is common and can be prevented by the continuous use of oral norfloxacin. The development of bacterial resistance demands the search for new options in the prophylaxis of spontaneous bacterial peritonitis; probiotics are a promising new approach, but deserve further evaluation. Short-term antibiotic prophylaxis is recommended for patients with cirrhosis and ascites shortly after an acute episode of gastrointestinal bleeding.

  10. Spontaneous Grammar Explanations.

    Science.gov (United States)

    Tjoo, Hong Sing; Lewis, Marilyn

    1998-01-01

    Describes one New Zealand university language teacher's reflection on her own grammar explanations to university-level students of Bahasa Indonesian. Examines form-focused instruction through the teacher's spontaneous answers to students' questions about the form of the language they are studying. The teacher's experiences show that it takes time…

  11. EDITORIAL SPONTANEOUS BACTERIAL PERITONITIS ...

    African Journals Online (AJOL)

    hi-tech

    Spontaneous bacterial peritonitis (SBP) frequent]y occurs in patients with liver cirrhosis and ascites. It is defined as an infection of previously sterile ascitic fluid without any demonstrable intrabdominal source of infection. It is now internationally agreed that a polymorphonuclear (PMN) cell count in the ascitic fluid of over 250 ...

  12. Spontaneous dimensional reduction?

    Science.gov (United States)

    Carlip, Steven

    2012-10-01

    Over the past few years, evidence has begun to accumulate suggesting that spacetime may undergo a "spontaneous dimensional reduction" to two dimensions near the Planck scale. I review some of this evidence, and discuss the (still very speculative) proposal that the underlying mechanism may be related to short-distance focusing of light rays by quantum fluctuations.

  13. The Effect of Creatine Kinase Inhibition on Contractile Properties of Human Resistance Arteries

    NARCIS (Netherlands)

    Taherzadeh, Zhila; Karamat, Fares A.; Ankum, Willem M.; Clark, Joseph F.; van Montfrans, Gert A.; van Bavel, Ed; Brewster, Lizzy M.

    2016-01-01

    Creatine kinase (CK) is a main predictor of blood pressure, and this is thought to largely depend on high resistance artery contractility. We previously reported an association between vascular contractility and CK in normotensive pregnancy, but pregnancy is a strong CK inducer, and data on human

  14. Reliability of contractile properties of the knee extensor muscles in individuals with post-polio syndrome

    NARCIS (Netherlands)

    Voorn, Eric L.; Brehm, Merel A.; Beelen, Anita; de Haan, Arnold; Nollet, Frans; Gerrits, Karin H. L.

    2014-01-01

    To assess the reliability of contractile properties of the knee extensor muscles in 23 individuals with post-polio syndrome (PPS) and 18 age-matched healthy individuals. Contractile properties of the knee extensors were assessed from repeated electrically evoked contractions on 2 separate days, with

  15. Free radicals in hypoxic rat diaphragm contractility: no role for xanthine oxidase.

    NARCIS (Netherlands)

    Heunks, L.M.A.; Machiels, H.A.; Abreu, R.A. de; Zhu, X.; Heijden, E. van der; Dekhuijzen, P.N.R.

    2001-01-01

    Recent evidence indicates that hypoxia enhances the generation of oxidants. Little is known about the role of free radicals in contractility of the rat diaphragm during hypoxia. We hypothesized that antioxidants improve contractility of the hypoxic rat diaphragm and that xanthine oxidase (XO) is an

  16. Effects of lengthening contraction on calcium kinetics and skeletal muscle contractility in humans

    DEFF Research Database (Denmark)

    Nielsen, J S; Madsen, K; Jørgensen, L V

    2005-01-01

    We have tested the hypothesis that the altered muscle contractility after lengthening contractions (LC) is caused by altered calcium (Ca2+) kinetics.......We have tested the hypothesis that the altered muscle contractility after lengthening contractions (LC) is caused by altered calcium (Ca2+) kinetics....

  17. Contractility of the guinea pig bladder measured in situ and in vitro

    NARCIS (Netherlands)

    J.M. Groen (Jan); R. van Mastrigt (Ron); J.L.H.R. Bosch (Ruud)

    1994-01-01

    textabstractTo study the relative importance of neurogenic factors in detrusor contractility and to relate a total bladder in vitro contractility model to a previously described bladder wall strip model, active intravesical pressure values were compared in situ and in vitro in eight male guinea

  18. The benefit of enhanced contractility in the infarct borderzone: A virtual experiment.

    Directory of Open Access Journals (Sweden)

    Zhihong eZhang

    2012-04-01

    Full Text Available A. Objectives Contractile function in the normally perfused infarct borderzone (BZ is depressed. However, the impact of reduced BZ contractility on left ventricular (LV pump function is unknown. As a consequence, there have been no therapies specifically designed to improve BZ contractility. We tested the hypothesis that an improvement in borderzone contractility will improve LV pump function.B. Methods From a previously reported study, magnetic resonance (MRI images with non-invasive tags were used to calculate 3D myocardial strain in five sheep 16 weeks after anteroapical myocardial infarction. Animal specific finite element (FE models were created using MRI data and LV pressure obtained at early diastolic filling. Analysis of borderzone function using those FE models has been previously reported. Chamber stiffness, pump function (Starling’s law and stress in the fiber, cross fiber and circumferential directions were calculated. Animal-specific FE models were performed for three cases: a impaired BZ contractility (INJURED; b BZ contractility fully restored (100% BZ IMPROVEMENT; or c BZ contractility partially restored (50% BZ IMPROVEMENT.C. Results 100% BZ IMPROVEMENT and 50% BZ IMPROVEMENT both caused an upward shift in the Starling relationship, resulting in a large (36% and 26% increase in stroke volume at LVPED = 20 mm Hg (8.0 ml, p<0.001. Moreover, there were a leftward shift in the end systolic pressure volume relationship, resulting in a 7% and 5% increase in LVPES at 110 mm Hg (7.7 ml, p<0.005. It showed that even 50% BZ IMPROVEMENT was sufficient to drive much of the calculated increase in function. D. Conclusions. Improved borderzone contractility has a beneficial effect on LV pump function. Partial improvement of borderzone contractility was sufficient to drive much of the calculated increase in function. Therapies specifically designed to improve borderzone contractility should be developed.

  19. The effects of watermelon (Citrullus lanatus) extracts and L-citrulline on rat uterine contractility.

    Science.gov (United States)

    Munglue, Phukphon; Eumkep, Graingsak; Wray, Susan; Kupittayanant, Sajeera

    2013-04-01

    In uterine smooth muscle, the effects of watermelon and its citrulline content are unknown. The aims of this study were therefore, to determine the effects of watermelon extract and citrulline on the myometrium and to investigate their mechanisms of action. The effects of extracts of watermelon flesh and rind and L-citrulline (64 μmol/L) were evaluated on 3 types of contractile activity; spontaneous, those elicited by potassium chloride (KCl) depolarization, or oxytocin (10 nmol/L) application in isolated rat uterus. Inhibitors of nitric oxide (NO) and its mechanisms of action, N ω-Nitro-L-arginine methyl ester hydrochloride (L-NAME, 100 μmol/L), LY83583 (1 μmol/L), and tetraethylamonium chloride (5 mmol/L), as well as Ca signaling pathways, were determined. Both flesh and rind extracts significantly decreased the force produced by all 3 mechanisms, in a dose-dependent manner. The extracts could also significantly decrease the force under conditions of sustained high Ca levels (depolarization and agonist) and when the force was produced only by sarcoplasmic reticulum (SR) Ca release. L-citrulline produced the same effects on force as watermelon extracts. With submaximal doses of extract, the additive effects of L-citrulline were found. The inhibitory effects of extracts and L-citrulline were reversed upon the addition of NO inhibitors, and pretreatment of tissues with these inhibitors prevented the actions of both extracts and L-citrulline. Thus, these data show that watermelon and citrulline are potent tocolytics, decreasing the force produced by calcium entry and SR release and arising by different pathways, including oxytocin stimulation. Their major mechanism is to stimulate the NO-cyclic guanosine monophosphate (cGMP) relaxant pathway.

  20. Cardiac contractility, central haemodynamics and blood pressure regulation during semistarvation

    DEFF Research Database (Denmark)

    Stokholm, K H; Breum, L; Astrup, A

    1991-01-01

    and equilibrium technique by [99Tcm]red blood cells). Cardiac output decreased concomitantly with the reduction in oxygen uptake as the calculated systemic arteriovenous difference of oxygen was unaltered. There were no significant decreases in left ventricular contractility indices, i.e. the ejection fraction......Eight obese patients were studied before and after 2 weeks of treatment by a very-low-calorie diet (VLCD). Cardiac output and central blood volume (pulmonary blood volume and left atrial volume) were determined by indicator dilution (125I-albumin) and radionuclide angiocardiography (first pass......, the peak ejection rate and changes in end-systolic volume. Also the diastolic function evaluated by the peak filling rate remained normal. Furthermore, no sign of backward failure could be demonstrated since the central blood volume was not significantly increased. Both systolic and diastolic blood...

  1. Contractile reaction of isolated frog aorta after X-irradiation

    International Nuclear Information System (INIS)

    Michailov, M.C.; Prechter, I.; Greimel, H.; Welscher, U.E.

    1983-01-01

    The action of X-rays (50 kV, filtered by 0.3 mm Al) on helical strip of frog aorta (rana esculenta) has been investigated. The isolated preparations have a stable basal tone and are radio-sensitive to X-rays which induce reversible, dose-dependent, contractile responses. After repeated irradiational tachyphylaxis appears. The threshold doses are about 250 R at 3 to 6 kR/min, antiadrenergic (phentolamine, propranolol), anticholinergic (atropin), antihistaminic (Neo-Bridal) and serotoninergic (Deseril) drugs have no visible influence on the X-ray induced reaction, i.e. these action mechanisms of the irradiation-induced contraction do not seem probable. Theophylline and cAMP inhibit the X-ray contraction probably non-specifically. Indometacin also inhibits the X-ray contraction: this suggests participation of prostaglandin-mechanism on the contraction of frog aorta after irradiation. (orig.) [de

  2. Contractile Changes in the Vasculature After Subchronic Smoking

    DEFF Research Database (Denmark)

    Haanes, Kristian Agmund; Kruse, Lars Schack; Johansson, Helle Wulf

    2016-01-01

    INTRODUCTION: Cigarette smoking is a well-known risk factor for developing cardiovascular diseases, but the underlying mechanisms are largely unknown. Recent data suggest that vasocontractile receptor modulation could be an important factor. Surfactant protein D (SP-D) is important in the particle...... clearance in the lungs and knock-out (KO) mice for this protein develop emphysema. SP-D is also weakly expressed in the vasculature. We aimed to investigate whether SP-D was important in the cardiovascular response to cigarette smoke exposure (CSE), by utilizing SP-D KO mice and a myograph setup. METHODS......: Wild type (WT) and SP-D KO mice were exposed to cigarette smoke (CS) or room air for 12 weeks. The pulmonary artery, left anterior descending coronary artery, and basilar artery (BA) were isolated and mounted in wire myographs. Contractile concentration response curves to endothelin-1 and UDP were...

  3. Redox regulation in skeletal muscle during contractile activity and aging.

    Science.gov (United States)

    Palomero, J; Jackson, M J

    2010-04-01

    Skeletal muscle has the ability to adapt and remodel after functional, mechanical, and metabolic stresses by activation of different adaptation mechanisms that induce gene expression, biochemical changes, and structural remodeling. Skeletal muscle cells continuously generate reactive oxygen and nitrogen species (RONS), which can act as mediators in cellular signaling pathways that regulate the adaptation mechanisms. There is strong evidence that indicates that RONS are generated in skeletal muscle cells during contractile activity and this induces the activation of transcription factors which modulate gene expression of antioxidant and protective proteins. Thus, it has been proposed that RONS act as signals that modulate the adaptation mechanisms in skeletal muscle and other cells. Structural and functional changes occur in skeletal muscle during aging and are characterized by a reduction of muscle mass and force (sarcopenia). The causes are known, however, there is considerable support for an involvement of RONS in the process of aging and sarcopenia. Several studies indicate that adaptive responses of skeletal muscle that are activated and regulated by RONS are disrupted during aging. This reduction of skeletal muscle adaptation to contractile activity during aging might be responsible for the loss of muscle mass and function and the progressive deterioration of this organ. In summary, there is sufficient evidence that indicates that cellular redox regulation in skeletal muscle is crucial in the physiology and pathology of skeletal muscle. However, new methodologies and experimental models are required for understanding the complex biology of RONS in the cell. This will provide future interventions that mitigate pathologies and aging of skeletal muscle.

  4. Contractile properties of early human embryonic stem cell-derived cardiomyocytes: beta-adrenergic stimulation induces positive chronotropy and lusitropy but not inotropy.

    Science.gov (United States)

    Pillekamp, Frank; Haustein, Moritz; Khalil, Markus; Emmelheinz, Markus; Nazzal, Rewa; Adelmann, Roland; Nguemo, Filomain; Rubenchyk, Olga; Pfannkuche, Kurt; Matzkies, Matthias; Reppel, Michael; Bloch, Wilhelm; Brockmeier, Konrad; Hescheler, Juergen

    2012-08-10

    Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) provide the unique opportunity to study the very early development of the human heart. The aim of this study was to investigate the effect of calcium and beta-adrenergic stimulation on the contractile properties of early hESC-CMs. Beating clusters containing hESC-CMs were co-cultured in vitro with noncontractile slices of neonatal murine ventricles. After 5-7 days, when beating clusters had integrated morphologically into the damaged tissue, isometric force measurements were performed during spontaneous beating as well as during electrical field stimulation. Spontaneous beating stopped when extracellular calcium ([Ca²⁺](ec)) was removed or after administration of the Ca²⁺ channel blocker nifedipine. During field stimulation at a constant rate, the developed force increased with incremental concentrations of [Ca²⁺](ec). During spontaneous beating, rising [Ca²⁺](ec) increased beating rate and developed force up to a [Ca²⁺](ec) of 2.5 mM. When [Ca²⁺](ec) was increased further, spontaneous beating rate decreased, whereas the developed force continued to increase. The beta-adrenergic agonist isoproterenol induced a dose-dependent increase of the frequency of spontaneous beating; however, it did not significantly change the developed force during spontaneous contractions or during electrical stimulation at a constant rate. Force developed by early hESC-CMs depends on [Ca²⁺](ec) and on the L-type Ca²⁺ channel. The lack of an inotropic reaction despite a pronounced chronotropic response after beta-adrenergic stimulation most likely indicates immaturity of the sarcoplasmic reticulum. For cell-replacement strategies, further maturation of cardiac cells has to be achieved either in vitro before or in vivo after transplantation.

  5. Spontaneous healing of spontaneous coronary artery dissection.

    Science.gov (United States)

    Almafragi, Amar; Convens, Carl; Heuvel, Paul Van Den

    2010-01-01

    Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome and sudden cardiac death. It should be suspected in every healthy young woman without cardiac risk factors, especially during the peripartum or postpartum periods. It is important to check for a history of drug abuse, collagen vascular disease or blunt trauma of the chest. Coronary angiography is essential for diagnosis and early management. We wonder whether thrombolysis might aggravate coronary dissection. All types of treatment (medical therapy, percutaneous intervention or surgery) improve the prognosis without affecting survival times if used appropriately according to the clinical stability and the angiographic features of the involved coronary arteries. Prompt recognition and targeted treatment improve outcomes. We report a case of SCAD in a young female free of traditional cardiovascular risk factors, who presented six hours after thrombolysis for ST elevation myocardial infarction. Coronary angiography showed a dissection of the left anterior descending and immediate branch. She had successful coronary artery bypass grafting, with complete healing of left anterior descending dissection.

  6. Eicosanomic profiling reveals dominance of the epoxygenase pathway in human amniotic fluid at term in spontaneous labor.

    Science.gov (United States)

    Maddipati, Krishna Rao; Romero, Roberto; Chaiworapongsa, Tinnakorn; Zhou, Sen-Lin; Xu, Zhonghui; Tarca, Adi L; Kusanovic, Juan Pedro; Munoz, Hernan; Honn, Kenneth V

    2014-11-01

    Lipid mediators play an important role in reproductive biology, especially, in parturition. Enhanced biosynthesis of eicosanoids, such as prostaglandin E2 (PGE2) and PGF2α, precedes the onset of labor as a result of increased expression of inducible cyclooxygenase 2 (COX-2) in placental tissues. Metabolism of arachidonic acid results in bioactive lipid mediators beyond prostaglandins that could significantly influence myometrial activity. Therefore, an unbiased lipidomic approach was used to profile the arachidonic acid metabolome of amniotic fluid. In this study, liquid chromatography-mass spectrometry was used for the first time to quantitate these metabolites in human amniotic fluid by comparing patients at midtrimester, at term but not in labor, and at term and in spontaneous labor. In addition to exposing novel aspects of COX pathway metabolism, this lipidomic study revealed a dramatic increase in epoxygenase- and lipoxygenase-pathway-derived lipid mediators in spontaneous labor with remarkable product selectivity. Despite their recognition as anti-inflammatory lipid mediators and regulators of ion channels, little is known about the epoxygenase pathway in labor. Epoxygenase pathway metabolites are established regulators of vascular homeostasis in cardiovascular and renal physiology. Their presence as the dominant lipid mediators in spontaneous labor at term portends a yet undiscovered physiological function in parturition. © FASEB.

  7. Calcium-induced contraction and contractile protein of gallbladder smooth muscle after high-cholesterol feeding of prairie dogs

    NARCIS (Netherlands)

    Li, Y. F.; Weisbrodt, N. W.; Moody, F. G.; Coelho, J. C.; Gouma, D. J.

    1987-01-01

    Feeding a high-cholesterol diet to prairie dogs causes a reduction in contractile responses of gallbladder smooth muscle from these animals. In this study, the influence of cholesterol feeding on the contractile response to calcium and on the concentration of the contractile proteins actin and

  8. Spontaneous spinal epidural abscess.

    LENUS (Irish Health Repository)

    Ellanti, P

    2011-10-01

    Spinal epidural abscess is an uncommon entity, the frequency of which is increasing. They occur spontaneously or as a complication of intervention. The classical triad of fever, back pain and neurological symptoms are not always present. High index of suspicion is key to diagnosis. Any delay in diagnosis and treatment can have significant neurological consequences. We present the case of a previously well man with a one month history of back pain resulting from an epidural abscess.

  9. Peritubular Contractile Cells in Testis and Epididymis of the Dog, Canis lupus familiaris

    Directory of Open Access Journals (Sweden)

    Gunter F. Egger

    2009-01-01

    Full Text Available Contractile cells surrounding the tubular system of the mammalian testis and epididymis are supposed to contribute to the initial transport of spermatozoa from the testis to epididymis. Testicular peritubular smooth muscle cells have been characterised in detail especially in rodents and humans. The aim of our study was to assess the distribution of peritubular contractile cells of the canine tubuli seminiferi, rete testis channels, ductuli efferentes, and ductus epididymidis by immunohistochemistry and transmission electron microscopy and to classify these cells with respect to their possible physiological function. The entire tubular system of the canine testis and epididymis is surrounded by contractile cells expressing smooth muscle actin, smooth muscle myosin and desmin, which are enveloped, at least partly, by a basal lamina. Some contractile cells of the tubuli seminiferi, rete channels, and efferent ducts and sometimes also single peritubular cells of the ductus epididymidis express vimentin. Contractile cells of seminiferous tubules and efferent ducts represent an intermediate cell type exhibiting characteristics of both smooth muscle cells (SMC and myofibroblasts, those of rete channels stellate myofibroblasts, and those of the ductus epididymidis SMC. Differences in structure and arrangement of the contractile cells between seminiferous tubules, rete channels, efferent ducts, and ductus epididymidis suggest different functions. Myofibroblasts and contractile cells similar to them could be mainly responsible for the maintenance of an appropriate tissue turgor, whereas contraction of SMC of the ductus epididymidis might cause propulsion of spermatozoa by peristaltic waves.

  10. Jackhammer esophagus: Assessing the balance between prepeak and postpeak contractile integral.

    Science.gov (United States)

    Xiao, Y; Carlson, D A; Lin, Z; Alhalel, N; Pandolfino, J E

    2017-11-29

    We hypothesized that symptoms in Jackhammer esophagus (JH) are associated with an imbalance between the prepeak and postpeak phases of contraction. Thus, we developed a method to distinguish the contractile integral components of prepeak and postpeak phase contractile activity to determine the contribution of each phase and their association with dysphagia. Patients diagnosed with JH were enrolled and compared to controls. The first five intact swallows during manometry were analyzed. A single swallow was divided into a prepeak and postpeak phase. The contractile integral of each phase and its corresponding time-controlled integral were computed. All metrics were compared between controls and JH patients subcategorized by the impaction dysphagia question (IDQ) score with cut-off of 6. Thirty eight JH patients and 71 controls were included. Twelve JH patients had IDQ ≤ 6 and 26 with IDQ > 6. JH patients had higher contractile integral in both phases, and a higher ratio between postpeak to prepeak contractile integral independent of duration. Similarly, JH patients with an IDQ > 6 had higher contractile metrics than those with IDQ ≤ 6. There was a correlation between the IDQ score and the ratio within the postpeak to prepeak contractile integral (r = .375). Abnormalities in contractile integral of the postpeak phase are more significant in JH with higher dysphagia scores Although the total postpeak contractile integral was higher in symptomatic patients, this was associated with longer duration of postpeak activity suggesting that dysphagia patients with JH have a defect in the postpeak phase of peristalsis. © 2017 John Wiley & Sons Ltd.

  11. Catecholamines and myocardial contractile function during hypodynamia and with an altered thyroid hormone balance

    Science.gov (United States)

    Pruss, G. M.; Kuznetsov, V. I.; Zhilinskaya, A. A.

    1980-01-01

    The dynamics of catecholamine content and myocardial contractile function during hypodynamia were studied in 109 white rats whose motor activity was severely restricted for up to 30 days. During the first five days myocardial catecholamine content, contractile function, and physical load tolerance decreased. Small doses of thyroidin counteracted this tendency. After 15 days, noradrenalin content and other indices approached normal levels and, after 30 days, were the same as control levels, although cardiac functional reserve was decreased. Thyroidin administration after 15 days had no noticeable effect. A detailed table shows changes in 17 indices of myocardial contractile function during hypodynamia.

  12. Tests of running performance do not predict subsequent spontaneous running in rats.

    Science.gov (United States)

    Lambert, M I; Van Zyl, C; Jaunky, R; Lambert, E V; Noakes, T D

    1996-07-01

    Rats of similar mass and genetic stock have up to a 50-fold difference in spontaneous daily running distance. However, the reasons for this large variability in spontaneous running distance are not known. This study examined whether tests of running performance predict subsequent spontaneous running distance in rats housed in individual running wheel cages. Long-Evans rats (n = 56) were randomly assigned to either a sedentary control group (C) or a group housed in specially designed wheel cages in which they were able to exercise spontaneously (ES). They then underwent a high-intensity running test (MAX), during which oxygen consumption was measured at a submaximal (VO2 submax) and maximal workload (VO2 max). The rats' submaximal running endurance (END) and maximal sprinting speed (SPRINT) were also tested on the treadmill. After 8 weeks the average spontaneous running distance of ES was 29.7 +/- 3.7 km.wk-1 (mean +/- SE), but ranged from 1.4 to 71.1 km.wk-1. Tests of running performance and oxygen consumption were repeated in both groups, followed by in situ measurements of muscle contractile properties and of citrate synthase activity in the skeletal muscle. None of the measurements of running performance or oxygen consumption during the initial tests conducted at the start of the experiment was related to subsequent average spontaneous running distance. After 8 weeks, the mean peak force generated by the electrically stimulated gastrocnemius/plantaris muscles was greater in ES than in C (746 +/- 89 vs. 455 +/- 28 mg, p SPRINT (r = 0.61, p < 0.0005) and was inversely related to running intensity (r = -0.66, p < 0.002) after 8 weeks of training. It can be concluded from this study that 1) spontaneous running distance in rats cannot be predicted by pretraining tests of running performance. Hence, low levels of spontaneous running activity in some rats are not explained by skeletal muscular and cardiovascular factors thought to determine running capacity, and 2

  13. Spontaneous Thigh Compartment Syndrome

    Directory of Open Access Journals (Sweden)

    Khan, Sameer K

    2011-02-01

    Full Text Available A young man presented with a painful and swollen thigh, without any history of trauma, illness, coagulopathic medication or recent exertional exercise. Preliminary imaging delineated a haematoma in the anterior thigh, without any fractures or muscle trauma. Emergent fasciotomies were performed. No pathology could be identified intra-operatively, or on follow-up imaging. A review of thigh compartment syndromes described in literature is presented in a table. Emergency physicians and traumatologists should be cognisant of spontaneous atraumatic presentations of thigh compartment syndrome, to ensure prompt referral and definitive management of this limb-threatening condition. [West J Emerg Med. 2011;12(1:134-138].

  14. Contractile Force of Human Extraocular Muscle: A Theoretical Analysis

    Directory of Open Access Journals (Sweden)

    Hongmei Guo

    2016-01-01

    Full Text Available Aim. The length-contractile force relationships of six human extraocular muscles (EOMs in primary innervations should be determined during eye movement modeling and surgery of clinical EOMs. This study aims to investigate these relationships. Method. The proposal is based on the assumption that six EOMs have similar constitutive relationships, with the eye suspended in the primary position. The constitutive relationships of EOMs are obtained by optimizing from previous experimental data and the theory of mechanical equilibrium using traditional model. Further, simulate the existing experiment of resistance force, and then compare the simulated results with the existing experimental results. Finally, the mechanical constitutive relationships of EOMs are obtained. Results. The results show that the simulated resistance forces from the other four EOMs except for the horizontal recti well agree with previous experimental results. Conclusion. The mechanical constitutive relationships of six EOMs in primary innervations are obtained, and the rationality of the constitutive relationships is verified. Whereafter, the active stress-strain relationships of the six EOMs in the primary innervations are obtained. The research results can improve the eye movement model to predict the surgical amounts of EOMs before EOM surgery more precisely.

  15. Contractility, differential tension and membrane removal lead zebrafish epiboly biomechanics.

    Science.gov (United States)

    Marsal, Maria; Hernández-Vega, Amayra; Martin-Blanco, Enrique

    2017-07-18

    Precise tissue remodeling during development is essential for shaping embryos and optimal organ function. Epiboly is an early gastrulation event by which the blastoderm expands around the yolk to engulf it. Three different layers are involved in this process, an epithelial layer (the enveloping layer, EVL), the embryo proper, constituted by the deep cells (DCs), and the yolk cell. Although teleost epiboly has been studied for many years, a clear understanding of its mechanics was still missing. Here we present new information on the cellular, molecular and mechanical elements involved in epiboly that, together with some other recent data and upon comparison with previous biomechanical models, lets conclude that the expansion of the epithelia is passive and driven by active cortical contraction and membrane removal in the adjacent layer, the External Yolk Syncytial Layer (E-YSL). The isotropic actomyosin contraction of the E-YSL cortex generates an anisotropic stress pattern and a directional net movement consequence of the differences in the deformation response of the 2 opposites adjacent domains (EVL and the Yolk Cytoplasmic Layer - YCL). Contractility is accompanied by the local formation of membrane folds and its removal by Rab5ab dependent macropinocytosis. The increase in area of the epithelia during the expansion is achieved by cell-shape changes (flattening) responding to spherical geometrical cues. The counterbalance between the geometry of the embryo and forces dissipation among different elements is therefore essential for epiboly global coordination.

  16. Mechanism of action of ethanol on heart contractility

    International Nuclear Information System (INIS)

    Oquendo-Muriente, I.; De Mello, W.C.

    1986-01-01

    Ethanol depresses heart contractility. To investigate the mechanism of the negative inotropic action of ethanol, rat ventricular strips were dissected and mounted vertically in a transparent chamber. The preparation was superfused initially with normal oxygenated Tyrode solution (32.5 0 C) and electrically stimulated (1 Hz). After 1 hour of equilibration, contractures were elicited by exposing the muscle strips to high K + (100 mM) solution. Studies on the influence of (Ca 2+ ) 0 on K + contractures showed that the first rapid component of the contracture (58 mg/sec - S.E. +/- 8; n = 8) was greatly dependent upon (Ca 2+ ) 0 while the second slow component (20 mg/sec - S.E. +/- 5; n = 8) was slightly altered. The addition of ethanol (400 mg/100 ml) to high K solution abolished the fast component and reduced the amplitude of the second phase of K contractures. Similar results were obtained with verapamil (10 -5 M). These results, as well as studies on the effect of the drug on 45 Ca fluxes support the view that ethanol decreases the permeability of the heart cell membrane to Ca

  17. Mechanism of action of ethanol on heart contractility

    Energy Technology Data Exchange (ETDEWEB)

    Oquendo-Muriente, I.; De Mello, W.C.

    1986-03-05

    Ethanol depresses heart contractility. To investigate the mechanism of the negative inotropic action of ethanol, rat ventricular strips were dissected and mounted vertically in a transparent chamber. The preparation was superfused initially with normal oxygenated Tyrode solution (32.5/sup 0/C) and electrically stimulated (1 Hz). After 1 hour of equilibration, contractures were elicited by exposing the muscle strips to high K/sup +/ (100 mM) solution. Studies on the influence of (Ca/sup 2 +/)/sub 0/ on K/sup +/ contractures showed that the first rapid component of the contracture (58 mg/sec - S.E. +/- 8; n = 8) was greatly dependent upon (Ca/sup 2 +/)/sub 0/ while the second slow component (20 mg/sec - S.E. +/- 5; n = 8) was slightly altered. The addition of ethanol (400 mg/100 ml) to high K solution abolished the fast component and reduced the amplitude of the second phase of K contractures. Similar results were obtained with verapamil (10/sup -5/ M). These results, as well as studies on the effect of the drug on /sup 45/Ca fluxes support the view that ethanol decreases the permeability of the heart cell membrane to Ca.

  18. Deactivation rate and shortening velocity as determinants of contractile frequency.

    Science.gov (United States)

    Marsh, R L

    1990-08-01

    The kinetic properties of muscle that could influence locomotor frequency include rate of activation, rate of cross-bridge "attachment", intrinsic shortening velocity, and rate of deactivation. The latter two mechanisms are examined using examples from high-speed running in lizards and escape swimming in scallops. During running, inertial loading and elastic energy storage probably mitigate the effects of thermal alterations in intrinsic muscle shortening velocity. The result is a rather low thermal dependence of stride frequency over a 15-20 degree C temperature range. However, at lower temperatures, the longer times required for deactivation cause the thermal dependence of frequency to increase greatly. Scallops use a single muscle to swim by jet propulsion. In vivo shortening velocity in these animals also shows a low thermal dependence. As with high-speed running, the mechanics of jet propulsion may limit the effects of thermally induced changes in intrinsic shortening velocity. The largest thermal effect during swimming is on the initial phase of valve opening. The effects of temperature on the rate of deactivation of the adductor muscle could play an important role in limiting reextension of the muscle, which is dependent on elastic energy storage in the hinge ligament. These examples illustrate that the relative importance of various intrinsic contractile properties in controlling locomotor performance depends on the mechanics of the movements.

  19. Reduced calcium responsiveness characterizes contractile dysfunction following coronary microembolization.

    Science.gov (United States)

    Skyschally, Andreas; Gres, Petra; van Caster, Patrick; van de Sand, Anita; Boengler, Kerstin; Schulz, Rainer; Heusch, Gerd

    2008-11-01

    We addressed calcium responsiveness in microembolized myocardium at 6 h after coronary microembolization (ME). In anesthetized pigs calcium responsiveness was determined as the increase of a myocardial work index (WI; LV pressure development vs. wall thickening) in response to a graded intracoronary infusion of CaCl(2) at baseline and at 6 h after ME or placebo, respectively. At baseline, CaCl(2 )infusion increased WI in both groups (ME: 296 +/- 22 to 468 +/- 47 mmHg*mm; placebo: 324 +/- 24 to 485 +/- 38 mmHg*mm; mean +/- SEM). At 6 h after ME, WI was decreased by 159 +/- 16 mmHg*mm (P < 0.05 vs. baseline) and remained reduced at any calcium concentration, whereas it was unchanged with placebo. The calcium concentration in coronary blood necessary to achieve the half maximal increase in WI remained unchanged from baseline to 6 h and did not differ between placebo and ME. The ME-induced myocardial dysfunction is not related to an altered calcium sensitivity, but is characterized by a reduced maximal contractile force.

  20. The contractility of elongated microvilli in early sea urchin embryos.

    Science.gov (United States)

    Spiegel, Evelyn; Howard, Louisa; Spiegel, Melvin

    1990-04-01

    Elongated microvilli attach the early sea urchin embryo to the fertilization envelope and support it in a concentric position within the perivitelline space. The contractility of the elongated microvilli was demonstrated in several ways. (1) During normal cleavage, these microvilli change their length to adapt to the change in shape and numbers of blastomeres. (2) When treated with calcium-free sea water, embryos become eccentrically located and the microvilli extend further than normal on one side; when returned to normal sea water, the embryos become centered again. (3) Several agents cause the fertilization envelope to become higher and thinner than normal and the elongated microvilli to extend correspondingly if treated within ten min after fertilization. In some cases, both elongated microvilli and fertilization envelope return to normal size when returned to normal sea water. (4) Fertilization in a papain solution causes the elongated microvilli and the fertilization envelope to contract to the surface of the embryo. (5) Refertilization after the papain-induced contraction can bring about the elongation of these microvilli and the elevation of the fertilization envelope a second time. It was also shown that elongated microvilli are extended immediately upon fertilization, at the same time as the short microvilli. The firm adherence of the tips of elongated microvilli to the fertilization envelope by means of extracellular matrix fibers is shown in a high voltage electron microscope stereoimage. This allows us to understand why it is that when the elongated microvilli extend or contract, the fertilization envelope also extends and contracts accordingly.

  1. Considerations for Contractile Electroactive Polymeric Materials and Actuators

    International Nuclear Information System (INIS)

    Rasmussen, L.; Erickson, Carl J.; Meixler, Lewis D.; Ascione, G.; Gentile, Charles A.; Tilson, C.; Bernasek, Stephen L.; Abelev, E.

    2009-01-01

    Ras Labs produces electroactive polymer (EAP) based materials and actuators that bend, swell, ripple and now contract (new development) with low electric input. This is an important attribute because of the ability of contraction to produce life-like motion. The mechanism of contraction is not well understood. Radionuclide-labeled experiments were conducted to follow the movement of electrolytes and water in these EAPs when activated. Extreme temperature experiments were performed on the contractile EAPs with very favorable results. One of the biggest challenges in developing these actuators, however, is the electrode-EAP interface because of the pronounced movement of the EAP. Plasma treatments of metallic electrodes were investigated in order to improve the attachment of the embedded electrodes to the EAP material. Surface analysis, adhesive testing, and mechanical testing were conducted to test metal surfaces and metal-polymer interfaces. The nitrogen plasma treatment of titanium produced a strong metal-polymer interface; however, oxygen plasma treatment of both stainless steel and titanium produced even stronger metal-polymer interfaces. Plasma treatment of the electrodes allows for the embedded electrodes and the EAP material of the actuator to work and move as a unit, with no detachment, by significantly improving the metal-polymer interface

  2. Considerations for Contractile Electroactive Polymeric Materials and Actuators

    Energy Technology Data Exchange (ETDEWEB)

    Rasmussen, Lenore; Erickson, Carl J.; Meixler, Lewis D.; Ascione, George; Gentile, Charles A.; Tilson, Charles; Bernasek, Stephen L.; Abelev, Esta

    2009-06-16

    Ras Labs produces electroactive polymer (EAP) based materials and actuators that bend, swell, ripple and now contract (new development) with low electric input. This is an important attribute because of the ability of contraction to produce life-like motion. The mechanism of contraction is not well understood. Radionuclide-labeled experiments were conducted to follow the movement of electrolytes and water in these EAPs when activated. Extreme temperature experiments were performed on the contractile EAPs with very favorable results. One of the biggest challenges in developing these actuators, however, is the electrode-EAP interface because of the pronounced movement of the EAP. Plasma treatments of metallic electrodes were investigated in order to improve the attachment of the embedded electrodes to the EAP material. Surface analysis, adhesive testing, and mechanical testing were conducted to test metal surfaces and metal-polymer interfaces. The nitrogen plasma treatment of titanium produced a strong metal-polymer interface; however, oxygen plasma treatment of both stainless steel and titanium produced even stronger metal-polymer interfaces. Plasma treatment of the electrodes allows for the embedded electrodes and the EAP material of the actuator to work and move as a unit, with no detachment, by significantly improving the metal-polymer interface.

  3. Modeling the dispersion effects of contractile fibers in smooth muscles

    Science.gov (United States)

    Murtada, Sae-Il; Kroon, Martin; Holzapfel, Gerhard A.

    2010-12-01

    Micro-structurally based models for smooth muscle contraction are crucial for a better understanding of pathological conditions such as atherosclerosis, incontinence and asthma. It is meaningful that models consider the underlying mechanical structure and the biochemical activation. Hence, a simple mechanochemical model is proposed that includes the dispersion of the orientation of smooth muscle myofilaments and that is capable to capture available experimental data on smooth muscle contraction. This allows a refined study of the effects of myofilament dispersion on the smooth muscle contraction. A classical biochemical model is used to describe the cross-bridge interactions with the thin filament in smooth muscles in which calcium-dependent myosin phosphorylation is the only regulatory mechanism. A novel mechanical model considers the dispersion of the contractile fiber orientations in smooth muscle cells by means of a strain-energy function in terms of one dispersion parameter. All model parameters have a biophysical meaning and may be estimated through comparisons with experimental data. The contraction of the middle layer of a carotid artery is studied numerically. Using a tube the relationships between the internal pressure and the stretches are investigated as functions of the dispersion parameter, which implies a strong influence of the orientation of smooth muscle myofilaments on the contraction response. It is straightforward to implement this model in a finite element code to better analyze more complex boundary-value problems.

  4. Adipose-derived stem cells inhibit the contractile myofibroblast in Dupuytren's disease.

    NARCIS (Netherlands)

    Verhoekx, J.S.; Mudera, V.; Walbeehm, E.T.; Hovius, S.E.

    2013-01-01

    BACKGROUND: In an attempt to provide minimally invasive treatment for Dupuytren's disease, percutaneous disruption of the affected tissue followed by lipografting is being tested. Contractile myofibroblasts drive this fibroproliferative disorder, whereas stem cells have recently been implicated in

  5. Spontaneous Tumor Lysis Syndrome

    Directory of Open Access Journals (Sweden)

    Alicia C. Weeks MD

    2015-08-01

    Full Text Available Tumor lysis syndrome (TLS is a known complication of malignancy and its treatment. The incidence varies on malignancy type, but is most common with hematologic neoplasms during cytotoxic treatment. Spontaneous TLS is thought to be rare. This case study is of a 62-year-old female admitted with multisystem organ failure, with subsequent diagnosis of aggressive B cell lymphoma. On admission, laboratory abnormalities included renal failure, elevated uric acid (20.7 mg/dL, and 3+ amorphous urates on urinalysis. Oliguric renal failure persisted despite aggressive hydration and diuretic use, requiring initiation of hemodialysis prior to chemotherapy. Antihyperuricemic therapy and hemodialysis were used to resolve hyperuricemia. However, due to multisystem organ dysfunction syndrome with extremely poor prognosis, the patient ultimately expired in the setting of a terminal ventilator wean. Although our patient did not meet current TLS criteria, she required hemodialysis due to uric acid nephropathy, a complication of TLS. This poses the clinical question of whether adequate diagnostic criteria exist for spontaneous TLS and if the lack of currently accepted guidelines has resulted in the underestimation of its incidence. Allopurinol and rasburicase are commonly used for prevention and treatment of TLS. Although both drugs decrease uric acid levels, allopurinol mechanistically prevents formation of the substrate rasburicase acts to solubilize. These drugs were administered together in our patient, although no established guidelines recommend combined use. This raises the clinical question of whether combined therapy is truly beneficial or, conversely, detrimental to patient outcomes.

  6. Platelets as Contractile Nanomachines for Targeting Drug Delivery in Hemostasis and Thrombosis

    Science.gov (United States)

    2015-12-01

    AWARD NUMBER: W81XWH-13-1-0495 TITLE: Platelets as Contractile Nanomachines for Targeting Drug Delivery in Hemostasis and Thrombosis PRINCIPAL...TITLE AND SUBTITLE 5a. CONTRACT NUMBER Platelets as Contractile Nanomachines for Targeting Drug Delivery in Hemostasis and Thrombosis 5b. GRANT...controlled nanocarriers as a novel and potentially paradigm-shifting strategy for targeted drug delivery to achieve hemostasis during bleeding. We have

  7. Effect of heart rate and myocardial contractile force on coronary resistance.

    OpenAIRE

    Saito, Daiji; Ueeda, Masayuki; Hina, Kazuyoshi; Watanabe, Hirofumi; Mima, Tsutomu; Hasui, Masahiro; Yamada, Nobuyuki; Haraoka, Shoichi; Tsuji, Takao

    1988-01-01

    The effect of the heart rate and myocardial contractile force on the extravascular resistance to blood flow of the left anterior descending coronary artery (LAD) was evaluated in 15 mongrel dogs anesthetized with sodium pentobarbital. The LAD was maximally dilated by intracoronary infusion of adenosine, which precluded the influence of vasomotor tone. Increases in the heart rate and myocardial contractile force decreased coronary blood flow in the absence of a change in coronary perfusion pre...

  8. A study of ventricular contractility and other parameters possibly related to vasodepressor syncope

    Science.gov (United States)

    Hyatt, K. H.; Sullivan, R. W.; Spears, W. R.; Vetter, W. R.

    1973-01-01

    The effects of diminished orthostatic and exercise tolerance resulting from prolonged bedrest were studied by noninvasion methods to determine if alterations in myocardial contractility were induced by bedrest. These methods were apexcardiography, systolic time intervals, and echocardiography. It is concluded that bedrest causes detrimental alterations in the contractile state of the myocardium which accounts for the decreases in maximal oxygen uptaken during exercise after bedrest. Tabulated test data are included.

  9. Escherichia coli-mediated impairment of ureteric contractility is uropathogenic E. coli specific.

    Science.gov (United States)

    Floyd, Rachel V; Upton, Mathew; Hultgren, Scott J; Wray, Susan; Burdyga, Theodor V; Winstanley, Craig

    2012-11-15

    Ureters are fundamental for keeping kidneys free from uropathogenic Escherichia coli (UPEC), but we have shown that 2 strains (J96 and 536) can subvert this role and reduce ureteric contractility. To determine whether this is (1) a widespread feature of UPEC, (2) exhibited only by UPEC, and (3) dependent upon type 1 fimbriae, we analyzed strains representing epidemiologically important multilocus sequence types ST131, ST73, and ST95 and non-UPEC E. coli. Contractility and calcium transients in intact rat ureters were compared between strains. Mannose and fim mutants were used to investigate the role of type 1 fimbriae. Non-UPEC had no significant effect on contractility, with a mean decrease after 8 hours of 8.8%, compared with 8.8% in controls. UPEC effects on contractility were strain specific, with decreases from 9.47% to 96.7%. Mannose inhibited the effects of the most potent strains (CFT073 and UTI89) but had variable effects among other UPEC strains. Mutation and complementation studies showed that the effects of the UTI89 cystitis isolate were fimH dependent. We find that (1) non-UPEC do not affect ureteric contractility, (2) impairment of contractility is a common feature of UPEC, and (3) the mechanism varies between strains, but for the most potent UPEC type 1 fimbriae are involved.

  10. A comparative study of contractility of the heart ventricle in some ectothermic vertebrates

    Directory of Open Access Journals (Sweden)

    Sergey Kharin

    2009-07-01

    Full Text Available The purpose of this study was to analyze contractility of the heart ventricle in selected reptilian and amphibian species having the same ventricular excitation pattern. Systolic time intervals and indices of contractility of the heart ventricle were measured in anaesthetized frogs, snakes, and tortoises by use of polycardiography. The electromechanical delay was significantly shorter in tortoises compared with the other two species. The isovolumetric contraction time in frogs was approximately twofold longer than in reptiles. The pre-ejection period was the longest in frogs and the shortest in tortoises, whereas snakes were intermediate. The ejection time was slightly longer in tortoises compared with the other two species. The greatest isovolumetric contraction index and the smallest myocardial tension index corresponded to the frog and tortoise heart ventricle, respectively. The intrasystolic index in tortoises was significantly greater than in frogs, whereas quite similar to that in snakes. The frog ventricle had lower contractility compared with the reptilian one. Although ventricular contractility tended to be lower in snakes compared with tortoises, this difference was not statistically significant. Possible causes for these differences are discussed. We suppose a large variety in ventricular contractility among amphibian and reptilian species having the same ventricular activation pattern. This variety may be conditioned by heart anatomy, intracardiac shunting, lifestyles, and habitats. It can only be hypothesized that on the average, ventricular contractility is higher in reptiles compared with amphibians and in chelonians compared with snakes.

  11. Reliability of contractile properties of the knee extensor muscles in individuals with post-polio syndrome.

    Directory of Open Access Journals (Sweden)

    Eric L Voorn

    Full Text Available To assess the reliability of contractile properties of the knee extensor muscles in 23 individuals with post-polio syndrome (PPS and 18 age-matched healthy individuals.Contractile properties of the knee extensors were assessed from repeated electrically evoked contractions on 2 separate days, with the use of a fixed dynamometer. Reliability was determined for fatigue resistance, rate of torque development (MRTD, and early and late relaxation time (RT50 and RT25, using the intraclass correlation coefficient (ICC and standard error of measurement (SEM, expressed as % of the mean.In both groups, reliability for fatigue resistance was good, with high ICCs (>0.90 and small SEM values (PPS: 7.1%, healthy individuals: 7.0%. Reliability for contractile speed indices varied, with the best values found for RT50 (ICCs>0.82, SEM values <2.8%. We found no systematic differences between test and retest occasions, except for RT50 in healthy subjects (p = 0.016.In PPS and healthy individuals, the reliability of fatigue resistance, as obtained from electrically evoked contractions is high. The reliability of contractile speed is only moderate, except for RT50 in PPS, demonstrating high reliability.This was the first study to examine the reliability of electrically evoked contractile properties in individuals with PPS. Our results demonstrate its potential to study mechanisms underlying muscle fatigue in PPS and to evaluate changes in contractile properties over time in response to interventions or from natural course.

  12. Reliability of contractile properties of the knee extensor muscles in individuals with post-polio syndrome.

    Science.gov (United States)

    Voorn, Eric L; Brehm, Merel A; Beelen, Anita; de Haan, Arnold; Nollet, Frans; Gerrits, Karin H L

    2014-01-01

    To assess the reliability of contractile properties of the knee extensor muscles in 23 individuals with post-polio syndrome (PPS) and 18 age-matched healthy individuals. Contractile properties of the knee extensors were assessed from repeated electrically evoked contractions on 2 separate days, with the use of a fixed dynamometer. Reliability was determined for fatigue resistance, rate of torque development (MRTD), and early and late relaxation time (RT50 and RT25), using the intraclass correlation coefficient (ICC) and standard error of measurement (SEM, expressed as % of the mean). In both groups, reliability for fatigue resistance was good, with high ICCs (>0.90) and small SEM values (PPS: 7.1%, healthy individuals: 7.0%). Reliability for contractile speed indices varied, with the best values found for RT50 (ICCs>0.82, SEM values <2.8%). We found no systematic differences between test and retest occasions, except for RT50 in healthy subjects (p = 0.016). In PPS and healthy individuals, the reliability of fatigue resistance, as obtained from electrically evoked contractions is high. The reliability of contractile speed is only moderate, except for RT50 in PPS, demonstrating high reliability. This was the first study to examine the reliability of electrically evoked contractile properties in individuals with PPS. Our results demonstrate its potential to study mechanisms underlying muscle fatigue in PPS and to evaluate changes in contractile properties over time in response to interventions or from natural course.

  13. Effects of Amoxicillin and Clavulanic Acid on the Spontaneous Mechanical Activity of Juvenile Rat Duodenum.

    Science.gov (United States)

    Ciciora, Steven L; Williams, Kent C; Gariepy, Cheryl E

    2015-09-01

    There are a limited number of medications for the treatment of foregut dysmotility. Enteral amoxicillin/clavulanic acid induces phase III duodenal contractions in a fasting pediatric patient. The mechanism by which this occurs is unknown. We examined the individual contributions of amoxicillin and clavulanic acid on the spontaneous mechanical activity of juvenile rat duodenum to better understand this phenomenon. Duodenal segments from juvenile rats were longitudinally attached to force transducers in organ baths. Samples were cumulatively exposed to amoxicillin or clavulanic acid. Separate samples were exposed to carbachol alone to assess response in both the presence and absence of amoxicillin or clavulanic acid. Basal tone, frequency, and amplitude of contractions were digitized and recorded. The amplitude of the spontaneous contractions increased with amoxicillin. Inhibition of neuronal activity prevented this effect. Clavulanic acid did not affect the spontaneous contractions. Basal tone and the rate of contractions did not differ with either drug. Stimulation with carbachol in the presence of amoxicillin caused a statistically significant increase in the contractility compared with carbachol alone. Amoxicillin alters the spontaneous longitudinal mechanical activity of juvenile rat duodenum. Our results suggest that amoxicillin modulates the spontaneous pattern of cyclic mechanical activity of duodenal smooth muscle through noncholinergic, neurally mediated mechanisms. Our work provides an initial physiologic basis for the therapeutic use of amoxicillin in patients with gastrointestinal dysmotility.

  14. Spontaneous Intracranial Hypotension

    International Nuclear Information System (INIS)

    Joash, Dr.

    2015-01-01

    Epidemiology is not only rare but an important cause of new daily persistent headaches among young & middle age individuals. The Etiology & Pathogenesis is generally caused by spinal CSF leak. Precise cause remains largely unknown, underlying structural weakness of spinal meninges is suspected. There are several MR Signs of Intracranial Hypotension that include:- diffuse pachymeningeal (dural) enhancement; bilateral subdural, effusion/hematomas; Downward displacement of brain; enlargement of pituitary gland; Engorgement of dural venous sinuses; prominence of spinal epidural venous plexus and Venous sinus thrombosis & isolated cortical vein thrombosis. The sum of volumes of intracranial blood, CSF & cerebral tissue must remain constant in an intact cranium. Treatment in Many cases can be resolved spontaneously or by use Conservative approach that include bed rest, oral hydration, caffeine intake and use of abdominal binder. Imaging Modalities for Detection of CSF leakage include CT myelography, Radioisotope cisternography, MR myelography, MR imaging and Intrathecal Gd-enhanced MR

  15. Spontaneous wave packet reduction

    International Nuclear Information System (INIS)

    Ghirardi, G.C.

    1994-06-01

    There are taken into account the main conceptual difficulties met by standard quantum mechanics in dealing with physical processes involving macroscopic system. It is stressed how J.A.Wheeler's remarks and lucid analysis have been relevant to pinpoint and to bring to its extreme consequences the puzzling aspects of quantum phenomena. It is shown how the recently proposed models of spontaneous dynamical reduction represent a consistent way to overcome the conceptual difficulties of the standard theory. Obviously, many nontrivial problems remain open, the first and more relevant one being that of generalizing the model theories considered to the relativistic case. This is the challenge of the dynamical reduction program. 43 refs, 2 figs

  16. Muscle fatigue in frog semitendinosus: alterations in contractile function

    Science.gov (United States)

    Thompson, L. V.; Balog, E. M.; Riley, D. A.; Fitts, R. H.

    1992-01-01

    The purpose of this study was to characterize the contractile properties of the frog semitendinosus (ST) muscle before and during recovery from fatigue, to relate the observed functional changes to alterations in specific steps in the crossbridge model of muscle contraction, and to determine how fatigue affects the force-frequency relationship. The frog ST (22 degrees C) was fatigued by direct electrical stimulation with 100-ms 150-Hz trains at 1/s for 5 min. The fatigue protocol reduced peak twitch (Pt) and tetanic (Po) force to 32 and 8.5% of initial force, respectively. The decline in Pt was less than Po, in part due to a prolongation in the isometric contraction time (CT), which increased to 300% of the initial value. The isometric twitch duration was greatly prolonged as reflected by the lengthened CT and the 800% increase in the one-half relaxation time (1/2RT). Both Pt and Po showed a biphasic recovery, a rapid initial phase (2 min) followed by a slower (40 min) return to the prefatigue force. CT and 1/2RT also recovered in two phases, returning to 160 and 265% of control in the first 5 min. CT returned to the prefatigue value between 35 and 40 min, whereas even at 60 min 1/2RT was 133% of control. The maximal velocity of shortening, determined by the slack test, was significantly reduced [from 6.7 +/- 0.5 to 2.5 +/- 0.4 optimal muscle length/s] at fatigue. The force-frequency relationship was shifted to the left, so that optimal frequency for generating Po was reduced.(ABSTRACT TRUNCATED AT 250 WORDS).

  17. LPS and cytokines inhibit rat cardiomyocyte contractility in vitro

    Science.gov (United States)

    Hobai, Ion A.; Morse, Justin C.; Siwik, Deborah A.; Colucci, Wilson S.

    2014-01-01

    Background Sepsis-induced cardiomyopathy (SIC) is thought to be the result of detrimental effects of inflammatory mediators on cardiac muscle. Here we studied the effects of prolonged (24 ± 4 h) exposure of adult rat ventricular myocytes (ARVM) to bacterial lipopolysaccharide (LPS) and inflammatory cytokines tumor necrosis factor (TNF) and interleukins-1 (IL-1) and -6 (IL-6). Materials and methods We measured sarcomere shortening (SS) and cellular calcium (Ca2+) transients (ΔCai, with fura-2AM) in isolated cardiomyocytes externally paced at 5Hz at 37 °C. Results SS decreased after incubation with LPS (100 µg/ml), IL-1 (100 ng/ml) and IL-6 (30 ng/ml), but not with lesser doses of these mediators, or TNF (10 –100 ng/ml). A combination of LPS (100 µg/ml), TNF, IL-1 and IL-6 (each 100 ng/ml; i.e. “Cytomix-100”) induced a maximal decrease in SS and ΔCai. Sarcoplasmic reticulum (SR) Ca2+ load (CaSR, measured with caffeine) was unchanged by Cytomix-100, however, SR fractional release (ΔCai/CaSR) was decreased. Underlying these effects, Ca2+ influx into the cell (via L-type Ca2+ channels) and Ca2+ extrusion via Na+/Ca2+ exchange were decreased by Cytomix-100. SR Ca2+ pump (SERCA) was not affected. Conclusions Prolonged exposure of ARVM to a mixture of LPS and inflammatory cytokines inhibits cell contractility. The effect is mediated by the inhibition of Ca2+ influx via LTCC, and partially opposed by the inhibition of Na+/Ca2+ exchange. Since both mechanisms are commonly seen in animal models of SIC, we conclude that prolonged challenge with Cytomix-100 of ARVM may represent an accurate in vitro model for SIC. PMID:25439505

  18. Lipopolysaccharide and cytokines inhibit rat cardiomyocyte contractility in vitro.

    Science.gov (United States)

    Hobai, Ion A; Morse, Justin C; Siwik, Deborah A; Colucci, Wilson S

    2015-02-01

    Sepsis-induced cardiomyopathy (SIC) is thought to be the result of detrimental effects of inflammatory mediators on the cardiac muscle. Here we studied the effects of prolonged (24 ± 4 h) exposure of adult rat ventricular myocytes (ARVM) to bacterial lipopolysaccharide (LPS) and inflammatory cytokines tumor necrosis factor (TNF) and interleukins-1 (IL-1) and IL-6. We measured sarcomere shortening (SS) and cellular calcium (Ca(2+)) transients (ΔCai, with fura-2 AM) in isolated cardiomyocytes externally paced at 5 Hz at 37°C. SS decreased after incubation with LPS (100 μg/mL), IL-1 (100 ng/mL), and IL-6 (30 ng/mL), but not with lesser doses of these mediators, or TNF (10-100 ng/mL). A combination of LPS (100 μg/mL), TNF, IL-1, and IL-6 (each 100 ng/mL; i.e., "Cytomix-100") induced a maximal decrease in SS and ΔCai. Sarcoplasmic reticulum (SR) Ca(2+) load (CaSR, measured with caffeine) was unchanged by Cytomix-100; however, SR fractional release (ΔCai/CaSR) was decreased. Underlying these effects, Ca(2+) influx into the cell (via L-type Ca(2+) channels, LTCC) and Ca(2+) extrusion via Na(+)/Ca(2+) exchange were decreased by Cytomix-100. SR Ca(2+) pump (SERCA) (SR Ca(2+) ATPase) was not affected. Prolonged exposure of ARVM to a mixture of LPS and inflammatory cytokines inhibits cell contractility. The effect is mediated by the inhibition of Ca(2+) influx via LTCC, and partially opposed by the inhibition of Na(+)/Ca(2+) exchange. Because both mechanisms are commonly seen in animal models of SIC, we conclude that prolonged challenge with Cytomix-100 of ARVM may represent an accurate in vitro model for SIC. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Characterisation of the contractile dynamics of the resting ex vivo urinary bladder of the pig.

    Science.gov (United States)

    Lentle, Roger G; Reynolds, Gordon W; Janssen, Patrick W M; Hulls, Corrin M; King, Quinten M; Chambers, John Paul

    2015-12-01

    To characterise the area and movements of ongoing spontaneous localised contractions in the resting porcine urinary bladder and relate these to ambient intravesical pressure (Pves ), to further our understanding of their genesis and role in accommodating incoming urine. We used image analysis to quantify the areas and movements of discrete propagating patches of contraction (PPCs) on the anterior, anterolateral and posterior surfaces of the urinary bladders of six pigs maintained ex vivo with small incremental increases in volume. We then correlated the magnitude of Pves and cyclic changes in Pves with parameters derived from spatiotemporal maps. Contractile movements in the resting bladder consisted only of PPCs that covered around a fifth of the surface of the bladder, commenced at various sites, and were of ≈6 s in duration. They propagated at around 6 mm/s, mainly across the anterior and lateral surface of the bladder by various, sometimes circular, routes in a quasi-stable rhythm, and did not traverse the trigone. The frequencies of these rhythms were low (3.15 cycles/min) and broadly similar to those of cyclic changes in Pves (3.55 cycles/min). Each PPC was associated with a region of stretching (positive strain rate) and these events occurred in a background of more constant strain. The amplitudes of cycles in Pves and the areas undergoing PPCs increased after a sudden increase in Pves but the frequency of cycles of Pves and of origin of PPCs did not change. Peaks in Pves cycles occurred when PPCs were traversing the upper half of the bladder, which was more compliant. The velocity of propagation of PPCs was similar to that of transverse propagation of action potentials in bladder myocytes and significantly greater than that reported in interstitial cells. The size of PPCs, their frequency and their rate of propagation were not affected by intra-arterial dosage with tetrodotoxin or lidocaine. The origin and duration of PPCs influence both Pves and cyclic

  20. Spontaneous compactification to homogeneous spaces

    International Nuclear Information System (INIS)

    Mourao, J.M.

    1988-01-01

    The spontaneous compactification of extra dimensions to compact homogeneous spaces is studied. The methods developed within the framework of coset space dimensional reduction scheme and the most general form of invariant metrics are used to find solutions of spontaneous compactification equations

  1. Screening for spontaneous preterm birth

    NARCIS (Netherlands)

    van Os, M.A.; van Dam, A.J.E.M.

    2015-01-01

    Preterm birth is the most important cause of perinatal morbidity and mortality worldwide. In this thesis studies on spontaneous preterm birth are presented. The main objective was to investigate the predictive capacity of mid-trimester cervical length measurement for spontaneous preterm birth in a

  2. Contractile effect of tachykinins on rabbit small intestine.

    Science.gov (United States)

    Valero, Marta Sofía; Fagundes, Diego Santos; Grasa, Laura; Arruebo, María Pilar; Plaza, Miguel Ángel; Murillo, María Divina

    2011-04-01

    To study the role of the tachykinin receptors in spontaneous contractions of longitudinal and circular smooth muscle from rabbit small intestine and to determine the mechanism of action of Substance P (SP). Rabbit duodenum, jejunum and ileum segments were prepared. The spontaneous contractions of longitudinal and circular smooth muscle were recorded using a computer via an isometric force transducer. The specific agonists and antagonists of tachykinin receptors were added into the organ bath. The agonists of tachykinin NK1 receptor (SP and [Sar9] SP), NK2 receptor (NKA and (β-Ala8)-NKA), and NK3 receptor (NKB and Senktide) all induced contractions in the small intestine. The contractions were diminished by NK1 receptor antagonist L-733,060, NK2 receptor antagonist GR-94800, and NK3 receptor antagonist SB 218795. Contractions caused by SP were also reduced by atropine, verapamil, PKC inhibitor staurosporine, and PLC inhibitor U73122. Ttachykinin NK1, NK2, and NK3 receptors mediate the contractions of the smooth muscle in rabbit intestine. Furthermore, SP acts directly on smooth muscle cells through the tachykinin NK1 receptor.

  3. Spontaneous Pneumomediastinum: Hamman Syndrome

    Directory of Open Access Journals (Sweden)

    Tushank Chadha, BS

    2018-04-01

    significant fat stranding. The image also showed an intraluminal stent traversing the gastric antrum and gastric pylorus with no indication of obstruction. Circumferential mural thickening of the gastric antrum and body were consistent with the patient’s history of gastric adenocarcinoma. The shotty perigastric lymph nodes with associated fat stranding, along the greater curvature of the distal gastric body suggested local regional nodal metastases and possible peritoneal carcinomatosis. The thoracic CT scans showed extensive pneumomediastinum that tracked into the soft tissues of the neck, which given the history of vomiting also raised concern for esophageal perforation. There was still no evidence of mediastinal abscess or fat stranding. Additionally, a left subclavian vein port catheter, which terminates with tip at the cavoatrial junction of the superior vena cava can also be seen on the image. Discussion: Spontaneous Pneumomediastinum, also known as Hamman syndrome, is defined by the uncommon incidence of free air in the mediastinum due to the bursting of alveoli, as a result of extended spells of shouting, coughing, or vomiting.1,2 The condition is diagnosed when a clear cause (aerodigestive rupture, barotrauma, infection secondary to gas-forming organisms3 for pneumomediastinum cannot be clearly identified on diagnostic studies. Macklin and Macklin were the first to note the pathogenesis of the syndrome and explained that the common denominator to spontaneous pneumomediastinum was that increased alveolar pressure leads to alveolar rupture.3 Common clinical findings for spontaneous pneumomediastinum include: chest pain, dyspnea, cough, and emesis.4 The condition is not always readily recognized on initial presentation in part for its rare incidence, estimated to be approximately 1 in every 44,500 ED patients3and also because of the non-specific presenting symptoms. For this patient, there was no clear singular cause, and therefore she received care for spontaneous

  4. [Mechanism of 17β-estrogen on intracellular free calcium regulation in smooth muscle cells at the endometrial-myometrial interface in uteri with adenomyosis].

    Science.gov (United States)

    Wang, Sha; Duan, Hua; Zhang, Ying; Wang, Liping; Zhang, Henghui; Li, Guoli

    2015-07-01

    To investigate the regulation mechanism of estrogen on the free calcium of smooth muscle cells at the endometrial-myometrial interface (EMI) in uteri with adenomyosis. From September 2011 to November 2012, 59 uterine myometrial specimens were obtained from 59 cases underwent hysterectomy, including 28 adenomyosis patients as adenomyosis (ADS) group and 31 patients with cervical intraepithelial neoplasia III as control group. EMI smooth muscle cells were cultured and loaded with calcium ion fluorescent probe fluo-4/AM. After treated with trisphosphate (IP3) receptor antagonist, blocker of sarcoplasmic reticulum calcium-adenosine triphosphate (ATP), depleted agent of the ryanodine receptor-operated Ca(2+), inhibitor of L-type calcium channel, inhibitor of Na(+)-Ca(2+) exchanger, the labeled cells were stimulated with estrogen. The changes of intracellular Ca(2+) fluorescence intensity were detected by laser scanning microscopy. The changes of intracellular Ca(2+) concentration was indicated by △F[Ca(2+)](i). (1) Under normal calcium conditions, after the stimulation of estrogen, intracellular Ca(2+) fluorescence intensity in ADS group and control group both increased than those without estrogen. The △F[Ca(2+)](i) in ADS group was 384 ± 26, and in the control group △F[Ca(2+)](i) was 235 ± 20. The △F[Ca(2+)](i) in ADS group was higher than that in the control (P calcium conditions, the △F[Ca(2+)](i) in ADS group was 207 ± 17, and in the control group △F[Ca(2+)](i) was 221 ± 19. The △F[Ca(2+)](i) in ADS group was almost the same with the increase in the control (P = 0.731). The △F[Ca(2+)](i) in ADS group was significantly decreased compared with the calcium condition (P calcium conditions (P = 0.060). (2) After treated with IP3 receptor antagonist, blocker of sarcoplasmic reticulum calcium-ATP, depleted agent of the ryanodine receptor-operated Ca(2+), the △F[Ca(2+)]i in both groups were significantly reduced (P calcium channel, the △F[Ca(2+)](i

  5. TRADD, TRAF2, RIP1 and TAK1 are required for TNF-α-induced pro-labour mediators in human primary myometrial cells.

    Science.gov (United States)

    Lim, Ratana; Barker, Gillian; Lappas, Martha

    2017-07-01

    TNF-α plays a central role in the processes of human labour and delivery. This study sought to determine the role of the adaptor proteins TNFR1-associated death domain protein (TRADD), TNF receptor-associated factor 2 (TRAF2), receptor interacting protein 1 (RIP1) and transforming growth factor beta-activated kinase 1 (TAK1) in TNF-α-induced formation of pro-labour mediators. Human primary myometrial cells were transfected with siRNA against TRADD (siTRADD), TRAF2 (siTRAF2), RIP1 (siRIP1) or TAK1 (siTAK1), treated with TNF-α, and assayed for pro-inflammatory mediators expression. siTRADD, siTRAF2, siRIP1 and siTAK1 significantly decreased TNF-α-induced IL-1α, IL-1β, IL-6, IL-8, MCP-1 mRNA expression and release of IL-6, IL-8 and MCP-1; and cyclooxygenase (COX)-2 expression and release of prostaglandin PGF 2α . There was a significant attenuation of TNF-α-induced expression of adhesion molecules ICAM-1 and VCAM-1 mRNA with siTRADD, siTRAF2 or siRIP1. siTRADD and siRIP1 significantly attenuated TNF-α-induced MMP-9 mRNA expression and release and nuclear factor κB (NF-κB) transcriptional activity. There was a significant increase in TNF-α-induced sVCAM-1 release, MMP-9 mRNA expression and NF-κB activity with siTAK1. TRADD, TRAF2, RIP1 and TAK1 are involved in TNF-α signalling in human myometrium. Further studies are required to determine whether inhibition of these proteins can prevent preterm birth. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Impact of Cardiac Contractility during Cerebral Blood Flow in Ischemia

    Directory of Open Access Journals (Sweden)

    Silver, Brian

    2011-05-01

    Full Text Available Objective: In cerebral regions affected by ischemia, intrinsic vascular autoregulation is often lost. Blood flow delivery depends upon cardiac function and may be influenced by neuro-endocrine mediated myocardial suppression. Our objective is to evaluate the relation between ejection fraction (EF and transcranial doppler (TCD peak systolic velocities (PSV in patients with cerebral ischemic events.Methods: We conducted a retrospective cohort study from an existing TCD registry. We evaluated patients admitted within 24 hours of onset of a focal neurological deficit who had an echocardiogram and TCD performed within 72 hours of admission.Results: We identified 58 patients from March to October 2003. Eighty-one percent (n=47 had a hospital discharge diagnosis of ischemic stroke and 18.9% (n=11 had a diagnosis of transient ischemic attack. Fourteen patients had systolic dysfunction (EF50% compared to those with systolic dysfunction (EF<50% was as follows: middle cerebral artery 62.0 + 28.6 cm/s vs. 51.0 + 23.3 cm/s, p=0.11; anterior cerebral artery 52.1 + 21.6 cm/s vs. 45.9 + 22.7 cm/s, p=0.28; internal carotid artery 56.5 + 20.1 cm/s vs. 46.4 + 18.4 cm/s, p=0.04; ophthalmic artery 18.6 + 7.2 cm/s vs. 15.3 + 5.2 cm/s, p=0.11; vertebral artery 34.0 + 13.9 cm/s vs. 31.6 + 15.0 cm/s, p=0.44.Conclusion: Cerebral blood flow in the internal carotid artery territory appears to be higher in cerebral ischemia patients with preserved left ventricular contractility. Our study was unable to differentiate pre-existing cardiac dysfunction from neuro-endocrine mediated myocardial stunning. Future research is necessary to better understand heart-brain interactions in this setting and to further explore the underlying mechanisms and consequences of neuro-endocrine mediated cardiac dysfunction. [West J Emerg Med. 2011;12(2:227-232.

  7. Spontaneous breaking of supersymmetry

    Energy Technology Data Exchange (ETDEWEB)

    Zumino, B.

    1981-12-01

    There has been recently a revival of interest in supersymmetric gauge theories, stimulated by the hope that supersymmetry might help in clarifying some of the questions which remain unanswered in the so called Grand Unified Theories and in particular the gauge hierarchy problem. In a Grand Unified Theory one has two widely different mass scales: the unification mass M approx. = 10/sup 15/GeV at which the unification group (e.g. SU(5)) breaks down to SU(3) x SU(2) x U(1) and the mass ..mu.. approx. = 100 GeV at which SU(2) x U(1) is broken down to the U(1) of electromagnetism. There is at present no theoretical understanding of the extreme smallness of the ratio ..mu../M of these two numbers. This is the gauge hierarchy problem. This lecture attempts to review the various mechanisms for spontaneous supersymmetry breaking in gauge theories. Most of the discussions are concerned with the tree approximation, but what is presently known about radiative correction is also reviewed.

  8. Spontaneous intracranial hypotension

    International Nuclear Information System (INIS)

    Haritanti, A.; Karacostas, D.; Drevelengas, A.; Kanellopoulos, V.; Paraskevopoulou, E.; Lefkopoulos, A.; Economou, I.; Dimitriadis, A.S.

    2009-01-01

    Spontaneous intracranial hypotension (SIH) is an uncommon but increasingly recognized syndrome. Orthostatic headache with typical findings on magnetic resonance imaging (MRI) are the key to diagnosis. Delayed diagnosis of this condition may subject patients to unnecessary procedures and prolong morbidity. We describe six patients with SIH and outline the important clinical and neuroimaging findings. They were all relatively young, 20-54 years old, with clearly orthostatic headache, minimal neurological signs (only abducent nerve paresis in two) and diffuse pachymeningeal gadolinium enhancement on brain MRI, while two of them presented subdural hygromas. Spinal MRI was helpful in detecting a cervical cerebrospinal fluid leak in three patients and dilatation of the vertebral venous plexus with extradural fluid collection in another. Conservative management resulted in rapid resolution of symptoms in five patients (10 days-3 weeks) and in one who developed cerebral venous sinus thrombosis, the condition resolved in 2 months. However, this rapid clinical improvement was not accompanied by an analogous regression of the brain MR findings that persisted on a longer follow-up. Along with recent literature data, our patients further point out that SIH, to be correctly diagnosed, necessitates increased alertness by the attending physician, in the evaluation of headaches

  9. Spontaneous lateral temporal encephalocele.

    Science.gov (United States)

    Tuncbilek, Gokhan; Calis, Mert; Akalan, Nejat

    2013-01-01

    A spontaneous encephalocele is one that develops either because of embryological maldevelopment or from a poorly understood postnatal process that permits brain herniation to occur. We here report a rare case of lateral temporal encephalocele extending to the infratemporal fossa under the zygomatic arch. At birth, the infant was noted to have a large cystic mass in the right side of the face. After being operated on initially in another center in the newborn period, the patient was referred to our clinic with a diagnosis of temporal encephalocele. He was 6 months old at the time of admission. Computerized tomography scan and magnetic resonance imaging studies revealed a 8 × 9 cm fluid-filled, multiloculated cystic mass at the right infratemporal fossa. No intracranial pathology or connection is seen. The patient was operated on to reduce the distortion effect of the growing mass. The histopathological examination of the sac revealed well-differentiated mature glial tissue stained with glial fibrillary acid protein. This rare clinical presentation of encephaloceles should be taken into consideration during the evaluation of the lateral facial masses in the infancy period, and possible intracranial connection should be ruled out before surgery to avoid complications.

  10. Effects of imatinib mesylate on the spontaneous activity generated by the guinea-pig prostate.

    Science.gov (United States)

    Lam, Michelle; Dey, Anupa; Lang, Richard J; Exintaris, Betty

    2013-08-01

    What's known on the subject? and what does the study add?: Several studies have examined the functional role of tyrosine kinase receptors in the generation of spontaneous activity in various segments of the gastrointestinal and urogenital tracts through the application of its inhibitor, imatinib mesylate (Glivec®), but results are fairly inconsistent. This is the first study detailing the effects of imatinib mesylate on the spontaneous activity in the young and ageing prostate gland. As spontaneous electrical activity underlies the spontaneous rhythmic prostatic contractions that occur at rest, elucidating the mechanisms involved in the regulation of the spontaneous electrical activity and the resultant phasic contractions could conceivably lead to the identification of better targets and the development of more specific therapeutic agents to treat prostate conditions. To investigate the effect of imatinib mesylate, a tyrosine kinase receptor inhibitor, in the generation of spontaneous electrical and contractile activity in the young and ageing guinea-pig prostate. Standard tension and intracellular recording were used to measure spontaneous contractions and slow waves, respectively from the guinea-pig prostate at varying concentrations of imatinib mesylate (1-50 μm). Imatinib mesylate (1-10 μm), did not significantly affect slow waves recorded in the prostate of both age groups but at 50 μm, the amplitude of slow waves from the ageing guinea-pig prostate was significantly reduced (P imatinib mesylate attenuated the amplitude and slowed the frequency of contractions in ageing guinea-pigs to 5.15% and 3.3% at 1 μm (n = 6); 21.1% and 20.8% at 5 μm (n = 8); 58.4% and 8.8% at 10 μm (n = 11); 72.7% and 60% at 50 μm (n = 5). A significant reduction in contractions but persistence of slow waves suggests imatinib mesylate may affect the smooth muscle contractile mechanism. Imatinib mesylate also significantly reduced contractions in the prostates of younger guinea

  11. Magnitude-dependent proliferation and contractility modulation of human bladder smooth muscle cells under physiological stretch.

    Science.gov (United States)

    Luo, De-Yi; Wazir, Romel; Du, Caigan; Tian, Ye; Yue, Xuan; Wei, Tang-Qiang; Wang, Kun-Jie

    2015-11-01

    The purpose of this study was to describe and test a kind of stretch pattern which is based on modified BOSE BioDynamic system to produce optimum physiological stretch during bladder cycle. Moreover, we aimed to emphasize the effects of physiological stretch's amplitude upon proliferation and contractility of human bladder smooth muscle cells (HBSMCs). HBSMCs were seeded onto silicone membrane and subjected to stretch simulating bladder cycle at the range of stretches and time according to customized software on modified BOSE BioDynamic bioreactor. Morphological changes were assessed using immunofluorescence and confocal laser scanning microscope. Cell proliferation and cell viability were determined by BrdU incorporation assay and Cell Counting Kit-8, respectively. Contractility of the cells was determined using collagen gel contraction assay. RT-PCR was used to assess phenotypic and contractility markers. HBSMCs were found to show morphologically spindle-shaped and orientation at various elongations in the modified bioreactor. Stretch-induced proliferation and viability depended on the magnitude of stretch, and stretches also regulate contractility and contraction markers in a magnitude-dependent manner. We described and tested a kind of stretch pattern which delivers physiological stretch implemented during bladder cycle. The findings also showed that mechanical stretch can promote magnitude-dependent morphological, proliferative and contractile modulation of HBSMCs in vitro.

  12. Bilateral spontaneous carotid artery dissection.

    Science.gov (United States)

    Townend, Bradley Scott; Traves, Laura; Crimmins, Denis

    2005-06-01

    Bilateral internal carotid artery dissections have been reported, but spontaneous bilateral dissections are rare. Internal carotid artery dissection can present with a spectrum of symptoms ranging from headache to completed stroke. Two cases of spontaneous bilateral carotid artery dissection are presented, one with headache and minimal symptoms and the other with a stroke syndrome. No cause could be found in either case, making the dissections completely spontaneous. Bilateral internal carotid artery dissection (ICAD) should be considered in young patients with unexplained head and neck pain with or without focal neurological symptoms and signs. The increasing availability of imaging would sustain the higher index of suspicion.

  13. Plasticity of TOM complex assembly in skeletal muscle mitochondria in response to chronic contractile activity.

    Science.gov (United States)

    Joseph, Anna-Maria; Hood, David A

    2012-03-01

    We investigated the assembly of the TOM complex within skeletal muscle under conditions of chronic contractile activity-induced mitochondrial biogenesis. Tom40 import into mitochondria was increased by chronic contractile activity, as was its time-dependent assembly into the TOM complex. These changes coincided with contractile activity-induced augmentations in the expression of key protein import machinery components Tim17, Tim23, and Tom22, as well as the cytosolic chaperone Hsp90. These data indicate the adaptability of the TOM protein import complex and suggest a regulatory role for the assembly of this complex in exercise-induced mitochondrial biogenesis. Copyright © 2011 Elsevier B.V. and Mitochondria Research Society. All rights reserved. All rights reserved.

  14. Contractile properties are disrupted in Becker muscular dystrophy, but not in limb girdle type 2I

    DEFF Research Database (Denmark)

    Løkken, Nicoline; Hedermann, Gitte; Thomsen, Carsten

    2016-01-01

    We investigated whether a linear relationship between muscle strength and cross-sectional area (CSA) is preserved in calf muscles of patients with Becker muscular dystrophy (BMD, n = 14) and limb-girdle type 2I muscular dystrophy (LGMD2I, n = 11), before and after correcting for muscle fat...... infiltration. The Dixon magnetic resonance imaging technique was used to quantify fat and calculate a fat-free contractile CSA. Strength was assessed by dynamometry. Muscle strength/CSA relationships were significantly lower in patients versus controls. The strength/contractile-CSA relationship was still...... severely lowered in BMD, but was almost normalized in LGMD2I. Our findings suggest close to intact contractile properties in LGMD2I, which are severely disrupted in BMD. Ann Neurol 2016;80:466-471....

  15. Effects of minoxidil and nitroprusside on reflex increases in myocardial contractility.

    Science.gov (United States)

    Robie, N W

    1978-01-01

    1 The effects of nitroprusside and minoxidil on increases in myocardial contractility resulting from carotid artery occlusion were investigated in anaesthetized dogs. The results were compared with those produced by intravenous influsion of noradrenaline. 2 Nitroprusside and minoxidil attenuated the pressor responses produced by carotid artery occlusion. 3 Nitroprusside, but not minoxidil, attenuated the maximal myocardial contractility resulting from carotid occlusion. 4 The pressor and contractility responses to noradrenaline infusion were unaffected by either agent. 5 Nitroprusside failed to alter the myocardial responses produced by dimethylphenylpiperazinium. 6 These results, in conjunction with those of other investigators who have demonstrated that nitroprusside does not affect the release of noradrenaline from adrenergic neurons, suggest that nitroprusside may inhibit sympathetic nervous system reflex activity via an afferent and/or central component. PMID:620094

  16. Spontaneous intraorbital hematoma: case report

    Directory of Open Access Journals (Sweden)

    Vinodan Paramanathan

    2010-12-01

    Full Text Available Vinodan Paramanathan, Ardalan ZolnourianQueen's Hospital NHS Foundation Trust, Burton on Trent, Staffordshire DE13 0RB, UKAbstract: Spontaneous intraorbital hematoma is an uncommon clinical entity seen in ophthalmology practice. It is poorly represented in the literature. Current evidence attributes it to orbital trauma, neoplasm, vascular malformations, acute sinusitis, and systemic abnormalities. A 65-year-old female presented with spontaneous intraorbital hematoma manifesting as severe ocular pains, eyelid edema, proptosis, and diplopia, without a history of trauma. Computer tomography demonstrated a fairly well defined extraconal lesion with opacification of the paranasal sinuses. The principal differential based on all findings was that of a spreading sinus infection and an extraconal tumor. An unprecedented finding of a spontaneous orbital hematoma was discovered when the patient was taken to theater. We discuss the rarity of this condition and its management.Keywords: hemorrhage, ophthalmology, spontaneous, intra-orbital, hematoma

  17. The Effects of Histamine H3 Receptors on Contractile Responses on Rat Gastric Fundus

    Directory of Open Access Journals (Sweden)

    Aşkın Hekimoğlu

    2006-01-01

    Full Text Available The aim of this study is to determine the effects of histamine receptors on the gastrointestinal system smooth muscle contractions and the role of histamine H3 receptors on these effects. İsolated rat gastric fundus preparations were hanged on isolated organ bath and histamine receptor agonist and anthagonists were added to the bath solution and the electrical field stimulation-induced contractile responses were evaluated. In our study groups after blocking one of the histamine receptors H1, H2,H3; contractile responses were observed. Then, other two receptors were blocked one by one or combination of them to observe the changes on the contractile responses given to the electrical stimulation .To blocke histamine receptors pyrilamine (10-6м as H1 receptor blocker, famotidine (10-6м as H2 receptor blocker and thioperamide (10-5м as H3 receptor blocker and various combination of them were used. All groups were treated with H3 receptor anthagonist thioperamide (10-5м and agonist (R-α-methylhistamine (RMHA on 10-8, 10-7, 10-6 ve 10-5 molar concentrations cumulatively to observe its mediator effects on contractile responses. We suggested that (R-α-methylhistamine mediates the inhibition on the contractile effects of rat gastric fundus. This conclusion was supported by these findings: a the selective agonists (RMHA caused a dumping of the contractile effect of acetylcholine; b the effect of (RMHA was prevented by the selective H3 receptor antagonist thioperamide.

  18. Accessory left atrial diverticulae: contractile properties depicted with 64-slice cine-cardiac CT.

    LENUS (Irish Health Repository)

    Killeen, Ronan P

    2012-02-01

    To assess the contractility of accessory left atrial appendages (LAAs) using multiphasic cardiac CT. We retrospectively analyzed the presence, location, size and contractile properties of accessory LAAs using multiphasic cardiac 64-slice CT in 102 consecutive patients (63 males, 39 females, mean age 57). Multiplanar reformats were used to create image planes in axial oblique, sagittal oblique and coronal oblique planes. For all appendages with an orifice diameter >or= 10 mm, axial and sagittal diameters and appendage volumes were recorded in atrial diastole and systole. Regression analysis was performed to assess which imaging appearances best predicted accessory appendage contractility. Twenty-three (23%) patients demonstrated an accessory LAA, all identified along the anterior LA wall. Dimensions for axial oblique (AOD) and sagittal oblique (SOD) diameters and sagittal oblique length (SOL) were 6.3-19, 3.4-20 and 5-21 mm, respectively. All appendages (>or=10 mm) demonstrated significant contraction during atrial systole (greatest diameter reduction was AOD [3.8 mm, 27%]). Significant correlations were noted between AOD-contraction and AOD (R = 0.57, P < 0.05) and SOD-contraction and AOD, SOD and SOL (R = 0.6, P < 0.05). Mean diverticulum volume in atrial diastole was 468.4 +\\/- 493 mm(3) and in systole was 171.2 +\\/- 122 mm(3), indicating a mean change in volume of 297.2 +\\/- 390 mm(3), P < 0.0001. Stepwise multiple regression analysis revealed SOL to be the strongest independent predictor of appendage contractility (R(2) = 0.86, P < 0.0001) followed by SOD (R(2) = 0.91, P < 0.0001). Accessory LAAs show significant contractile properties on cardiac CT. Those accessory LAAs with a large sagittal height or depth should be evaluated for contractile properties, and if present should be examined for ectopic activity during electrophysiological studies.

  19. Smoothelin-B deficiency results in reduced arterial contractility, hypertension, and cardiac hypertrophy in mice.

    Science.gov (United States)

    Rensen, Sander S; Niessen, Petra M; van Deursen, Jan M; Janssen, Ben J; Heijman, Edwin; Hermeling, Evelien; Meens, Merlijn; Lie, Natascha; Gijbels, Marion J; Strijkers, Gustav J; Doevendans, Pieter A; Hofker, Marten H; De Mey, Jo G R; van Eys, Guillaume J

    2008-08-19

    Smoothelins are actin-binding proteins that are abundantly expressed in healthy visceral (smoothelin-A) and vascular (smoothelin-B) smooth muscle. Their expression is strongly associated with the contractile phenotype of smooth muscle cells. Analysis of mice lacking both smoothelins (Smtn-A/B(-/-) mice) previously revealed a critical role for smoothelin-A in intestinal smooth muscle contraction. Here, we report on the generation and cardiovascular phenotype of mice lacking only smoothelin-B (Smtn-B(-/-)). Myograph studies revealed that the contractile capacity of the saphenous and femoral arteries was strongly reduced in Smtn-B(-/-) mice, regardless of the contractile agonist used to trigger contraction. Arteries from Smtn-A/B(-/-) compound mutant mice exhibited a similar contractile deficit. Smtn-B(-/-) arteries had a normal architecture and expressed normal levels of other smooth muscle cell-specific genes, including smooth muscle myosin heavy chain, alpha-smooth muscle actin, and smooth muscle-calponin. Decreased contractility of Smtn-B(-/-) arteries was paradoxically accompanied by increased mean arterial pressure (20 mm Hg) and concomitant cardiac hypertrophy despite normal parasympathetic and sympathetic tone in Smtn-B(-/-) mice. Magnetic resonance imaging experiments revealed that cardiac function was not changed, whereas distension of the proximal aorta during the cardiac cycle was increased in Smtn-B(-/-) mice. However, isobaric pulse wave velocity and pulse pressure measurements indicated normal aortic distensibility. Collectively, our results identify smoothelins as key determinants of arterial smooth muscle contractility and cardiovascular performance. Studies on mutations in the Smtn gene or alterations in smoothelin levels in connection to hypertension in humans are warranted.

  20. Store-operated Ca2+ entry supports contractile function in hearts of hibernators.

    Directory of Open Access Journals (Sweden)

    Olga V Nakipova

    Full Text Available Hibernators have a distinctive ability to adapt to seasonal changes of body temperature in a range between 37°C and near freezing, exhibiting, among other features, a unique reversibility of cardiac contractility. The adaptation of myocardial contractility in hibernation state relies on alterations of excitation contraction coupling, which becomes less-dependent from extracellular Ca2+ entry and is predominantly controlled by Ca2+ release from sarcoplasmic reticulum, replenished by the Ca2+-ATPase (SERCA. We found that the specific SERCA inhibitor cyclopiazonic acid (CPA, in contrast to its effect in papillary muscles (PM from rat hearts, did not reduce but rather potentiated contractility of PM from hibernating ground squirrels (GS. In GS ventricles we identified drastically elevated, compared to rats, expression of Orai1, Stim1 and Trpc1/3/4/5/6/7 mRNAs, putative components of store operated Ca2+ channels (SOC. Trpc3 protein levels were found increased in winter compared to summer GS, yet levels of Trpc5, Trpc6 or Trpc7 remained unchanged. Under suppressed voltage-dependent K+, Na+ and Ca2+ currents, the SOC inhibitor 2-aminoethyl diphenylborinate (2-APB diminished whole-cell membrane currents in isolated cardiomyocytes from hibernating GS, but not from rats. During cooling-reheating cycles (30°C-7°C-30°C of ground squirrel PM, 2-APB did not affect typical CPA-sensitive elevation of contractile force at low temperatures, but precluded the contractility at 30°C before and after the cooling. Wash-out of 2-APB reversed PM contractility to control values. Thus, we suggest that SOC play a pivotal role in governing the ability of hibernator hearts to maintain their function during the transition in and out of hibernating states.

  1. Spontaneous ischaemic stroke in dogs

    DEFF Research Database (Denmark)

    Gredal, Hanne Birgit; Skerritt, G. C.; Gideon, P.

    2013-01-01

    Translation of experimental stroke research into the clinical setting is often unsuccessful. Novel approaches are therefore desirable. As humans, pet dogs suffer from spontaneous ischaemic stroke and may hence offer new ways of studying genuine stroke injury mechanisms.......Translation of experimental stroke research into the clinical setting is often unsuccessful. Novel approaches are therefore desirable. As humans, pet dogs suffer from spontaneous ischaemic stroke and may hence offer new ways of studying genuine stroke injury mechanisms....

  2. Spontaneity and international marketing performance

    OpenAIRE

    Souchon, Anne L.; Hughes, Paul; Farrell, Andrew M.; Nemkova, Ekaterina; Oliveira, Joao S.

    2016-01-01

    The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. Purpose – The purpose of this paper is to ascertain how today’s international marketers can perform better on the global scene by harnessing spontaneity. Design/methodology/approach – The authors draw on contingency theory to develop a model of the spontaneity – international marketing performance relationship, and identify three potential m...

  3. Validation of an in vitro contractility assay using canine ventricular myocytes

    Energy Technology Data Exchange (ETDEWEB)

    Harmer, A.R., E-mail: alex.harmer@astrazeneca.com; Abi-Gerges, N.; Morton, M.J.; Pullen, G.F.; Valentin, J.P.; Pollard, C.E.

    2012-04-15

    Measurement of cardiac contractility is a logical part of pre-clinical safety assessment in a drug discovery project, particularly if a risk has been identified or is suspected based on the primary- or non-target pharmacology. However, there are limited validated assays available that can be used to screen several compounds in order to identify and eliminate inotropic liability from a chemical series. We have therefore sought to develop an in vitro model with sufficient throughput for this purpose. Dog ventricular myocytes were isolated using a collagenase perfusion technique and placed in a perfused recording chamber on the stage of a microscope at ∼ 36 °C. Myocytes were stimulated to contract at a pacing frequency of 1 Hz and a digital, cell geometry measurement system (IonOptix™) was used to measure sarcomere shortening in single myocytes. After perfusion with vehicle (0.1% DMSO), concentration–effect curves were constructed for each compound in 4–30 myocytes taken from 1 or 2 dog hearts. The validation test-set was 22 negative and 8 positive inotropes, and 21 inactive compounds, as defined by their effect in dog, cynolomolgous monkey or humans. By comparing the outcome of the assay to the known in vivo contractility effects, the assay sensitivity was 81%, specificity was 75%, and accuracy was 78%. With a throughput of 6–8 compounds/week from 1 cell isolation, this assay may be of value to drug discovery projects to screen for direct contractility effects and, if a hazard is identified, help identify inactive compounds. -- Highlights: ► Cardiac contractility is an important physiological function of the heart. ► Assessment of contractility is a logical part of pre-clinical drug safety testing. ► There are limited validated assays that predict effects of compounds on contractility. ► Using dog myocytes, we have developed an in vitro cardiac contractility assay. ► The assay predicted the in vivo contractility with a good level of accuracy.

  4. Effects of ageing on single muscle fibre contractile function following short-term immobilisation

    DEFF Research Database (Denmark)

    Hvid, Lars G; Ørtenblad, Niels; Aagaard, Per

    2011-01-01

    Very little attention has been given to the combined effect of healthy ageing and short-term disuse on the contractile function of human single muscle fibres. Therefore, the present study investigated the effects of 2 weeks of lower limb cast immobilisation (i.e. disuse) on selected contractile...... properties of single muscle fibres (n=378) from vastus lateralis of 9 young (24 ± 1 years) and 8 old (67 ± 2 years) healthy men with comparable levels of physical activity. Prior to immobilisation, MHC IIa fibres produced higher maximum Ca2+-activated force (approx. 32%) and specific force (approx. 33......%) and had lower Ca2+ sensitivity than MHC I fibres (p...

  5. The GSTM2 C-Terminal Domain Depresses Contractility and Ca2+ Transients in Neonatal Rat Ventricular Cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Ruwani P Hewawasam

    Full Text Available The cardiac ryanodine receptor (RyR2 is an intracellular ion channel that regulates Ca2+ release from the sarcoplasmic reticulum (SR during excitation-contraction coupling in the heart. The glutathione transferases (GSTs are a family of phase II detoxification enzymes with additional functions including the selective inhibition of RyR2, with therapeutic implications. The C-terminal half of GSTM2 (GSTM2C is essential for RyR2 inhibition, and mutations F157A and Y160A within GSTM2C prevent the inhibitory action. Our objective in this investigation was to determine whether GSTM2C can enter cultured rat neonatal ventricular cardiomyocytes and influence contractility. We show that oregon green-tagged GSTM2C (at 1 μM is internalized into the myocytes and it reduces spontaneous contraction frequency and myocyte shortening. Field stimulation of myocytes evoked contraction in the same percentage of myocytes treated either with media alone or media plus 15 μM GSTM2C. Myocyte shortening during contraction was significantly reduced by exposure to 15 μM GSTM2C, but not 5 and 10 μM GSTM2C and was unaffected by exposure to 15 μM of the mutants Y160A or F157A. The amplitude of the Ca2+ transient in the 15 μM GSTM2C - treated myocytes was significantly decreased, the rise time was significantly longer and the decay time was significantly shorter than in control myocytes. The Ca2+ transient was not altered by exposure to Y160A or F157A. The results are consistent with GSTM2C entering the myocytes and inhibiting RyR2, in a manner that indicates a possible therapeutic potential for treatment of arrhythmia in the neonatal heart.

  6. A case of spontaneous ventriculocisternostomy

    International Nuclear Information System (INIS)

    Yamane, Kanji; Yoshimoto, Hisanori; Harada, Kiyoshi; Uozumi, Tohru; Kuwabara, Satoshi.

    1983-01-01

    The authors experienced a case of spontaneous ventriculocisternostomy diagnosed by CT scan with metrizamide and Conray. Patient was 23-year-old male who had been in good health until one month before admission, when he began to have headache and tinnitus. He noticed bilateral visual acuity was decreased about one week before admission and vomiting appeared two days before admission. He was admitted to our hospital because of bilateral papilledema and remarkable hydrocephalus diagnosed by CT scan. On admission, no abnormal neurological signs except for bilateral papilledema were noted. Immediately, right ventricular drainage was performed. Pressure of the ventricle was over 300mmH 2 O and CSF was clear. PVG and PEG disclosed an another cavity behind the third ventricle, which was communicated with the third ventricle, and occlusion of aqueduct of Sylvius. Metrizamide CT scan and Conray CT scan showed a communication between this cavity and quadrigeminal and supracerebellar cisterns. On these neuroradiological findings, the diagnosis of obstructive hydrocephalus due to benign aqueduct stenosis accompanied with spontaneous ventriculocisternostomy was obtained. Spontaneous ventriculocisternostomy was noticed to produce arrest of hydrocephalus, but with our case, spontaneous regression of such symptoms did not appeared. By surgical ventriculocisternostomy (method by Torkildsen, Dandy, or Scarff), arrest of hydrocephalus was seen in about 50 to 70 per cent, which was the same results as those of spontaneous ventriculocisternostomy. It is concluded that VP shunt or VA shunt is thought to be better treatment of obstructive hydrocephalus than the various kinds of surgical ventriculocisternostomy. (J.P.N.)

  7. Optical antenna enhanced spontaneous emission.

    Science.gov (United States)

    Eggleston, Michael S; Messer, Kevin; Zhang, Liming; Yablonovitch, Eli; Wu, Ming C

    2015-02-10

    Atoms and molecules are too small to act as efficient antennas for their own emission wavelengths. By providing an external optical antenna, the balance can be shifted; spontaneous emission could become faster than stimulated emission, which is handicapped by practically achievable pump intensities. In our experiments, InGaAsP nanorods emitting at ∼ 200 THz optical frequency show a spontaneous emission intensity enhancement of 35 × corresponding to a spontaneous emission rate speedup ∼ 115 ×, for antenna gap spacing, d = 40 nm. Classical antenna theory predicts ∼ 2,500 × spontaneous emission speedup at d ∼ 10 nm, proportional to 1/d(2). Unfortunately, at d antenna efficiency drops below 50%, owing to optical spreading resistance, exacerbated by the anomalous skin effect (electron surface collisions). Quantum dipole oscillations in the emitter excited state produce an optical ac equivalent circuit current, I(o) = qω|x(o)|/d, feeding the antenna-enhanced spontaneous emission, where q|x(o)| is the dipole matrix element. Despite the quantum-mechanical origin of the drive current, antenna theory makes no reference to the Purcell effect nor to local density of states models. Moreover, plasmonic effects are minor at 200 THz, producing only a small shift of antenna resonance frequency.

  8. A device for rapid and quantitative measurement of cardiac myocyte contractility

    Science.gov (United States)

    Gaitas, Angelo; Malhotra, Ricky; Li, Tao; Herron, Todd; Jalife, José

    2015-03-01

    Cardiac contractility is the hallmark of cardiac function and is a predictor of healthy or diseased cardiac muscle. Despite advancements over the last two decades, the techniques and tools available to cardiovascular scientists are limited in their utility to accurately and reliably measure the amplitude and frequency of cardiomyocyte contractions. Isometric force measurements in the past have entailed cumbersome attachment of isolated and permeabilized cardiomyocytes to a force transducer followed by measurements of sarcomere lengths under conditions of submaximal and maximal Ca2+ activation. These techniques have the inherent disadvantages of being labor intensive and costly. We have engineered a micro-machined cantilever sensor with an embedded deflection-sensing element that, in preliminary experiments, has demonstrated to reliably measure cardiac cell contractions in real-time. Here, we describe this new bioengineering tool with applicability in the cardiovascular research field to effectively and reliably measure cardiac cell contractility in a quantitative manner. We measured contractility in both primary neonatal rat heart cardiomyocyte monolayers that demonstrated a beat frequency of 3 Hz as well as human embryonic stem cell-derived cardiomyocytes with a contractile frequency of about 1 Hz. We also employed the β-adrenergic agonist isoproterenol (100 nmol l-1) and observed that our cantilever demonstrated high sensitivity in detecting subtle changes in both chronotropic and inotropic responses of monolayers. This report describes the utility of our micro-device in both basic cardiovascular research as well as in small molecule drug discovery to monitor cardiac cell contractions.

  9. Intestine of dystrophic mice presents enhanced contractile resistance to stretching despite morphological impairment.

    Science.gov (United States)

    Alves, Gabriel A; Silva, Luisa R; Rosa, Eloi F; Aboulafia, Jeannine; Freymüller-Haapalainen, Edna; Souccar, Caden; Nouailhetas, Viviane L A

    2014-02-01

    Protein dystrophin is a component of the dystrophin-associated protein complex, which links the contractile machinery to the plasma membrane and to the extracellular matrix. Its absence leads to a condition known as Duchenne muscular dystrophy (DMD), a disease characterized by progressive skeletal muscle degeneration, motor disability, and early death. In mdx mice, the most common DMD animal model, loss of muscle cells is observed, but the overall disease alterations are less intense than in DMD patients. Alterations in gastrointestinal tissues from DMD patients and mdx mice are not yet completely understood. Thus, we investigated the possible relationships between morphological (light and electron microscopy) and contractile function (by recording the isometric contractile response) with alterations in Ca²⁺ handling in the ileum of mdx mice. We evidenced a 27% reduction in the ileal muscular layer thickness, a partial damage to the mucosal layer, and a partial damage to mitochondria of the intestinal myocytes. Functionally, the ileum from mdx presented an enhanced responsiveness during stretch, a mild impairment in both the electromechanical and pharmacomechanical signaling associated with altered calcium influx-induced contraction, with no alterations in the sarcoplasmic reticulum Ca²⁺ storage (maintenance of the caffeine and thapsigargin-induced contraction) compared with control animals. Thus, it is evidenced that the protein dystrophin plays an important role in the preservation of both the microstructure and ultrastructure of mice intestine, while exerting a minor but important role concerning the intestinal contractile responsiveness and calcium handling.

  10. Hydrogen ion changes and contractile behavior in the perfused rat heart

    NARCIS (Netherlands)

    Cingolani, H.E.; Maas, A.H.J.; Zimmerman, A.N.E.; Meijler, F.L.

    1975-01-01

    The effect of acid-base alterations was analyzed using isolated rat hearts perfused at constant coronary perfusion pressure, and stimulated to contract at constant rate. The amount of shortening in the major axis and its derivative were measured to assess myocardial contractility. Both the

  11. Clinical comparison of bladder contractility parameters calculated from isometric contractions and pressure-flow studies

    NARCIS (Netherlands)

    R. van Mastrigt (Ron); D.J. Griffiths (Derek)

    1987-01-01

    textabstractParameters describing the contractility of the urinary bladder can be calculated from both isometric contractions and pressure-flow studies. The first method has the advantage of making very little demand either on the patient or on the urodynamicist, and the disadvantage of yielding a

  12. Transforming growth factor-beta 1 specifically induce proteins involved in the myofibroblast contractile apparatus

    DEFF Research Database (Denmark)

    Malmström, Johan; Lindberg, Henrik Have; Lindberg, Claes

    2004-01-01

    is to participate in the depolymerization and stabilization of the microfilaments. These results show that TGF-beta(1) induces not only alpha-SMA but a whole set of actin-associated proteins that may contribute to the increased contractile properties of the myofibroblast. These proteins accompany the induced...

  13. Contractile speed and fatigue of adductor pollicis muscle in multiple sclerosis.

    NARCIS (Netherlands)

    Ruiter, C.J. de; Jongen, P.J.H.; Woude, L.H.V. van der; Haan, A. de

    2001-01-01

    The purpose of the study was to investigate differences in contractile speed, force, and fatigability of the adductor pollicis muscle between 12 patients with multiple sclerosis (MS) and 8 sedentary control subjects matched for age and gender. There were no differences between the patients with MS

  14. Contractile speed and fatigue of adductor pollicis muscle in multiple sclerosis

    NARCIS (Netherlands)

    de Ruiter, C.J.; Jongen, P.J.H.; van der Woude, L.H.V.; de Haan, A.

    2001-01-01

    The purpose of the study was to investigate differences in contractile speed, force, and fatigability of the adductor pollicis muscle between 12 patients with multiple sclerosis (MS) and 8 sedentary control subjects matched for age and gender. There were no differences between the patients with MS

  15. Analysis of Contractility and Invasion Potential of Two Canine Mammary Tumor Cell Lines

    Directory of Open Access Journals (Sweden)

    Kaisa Rajakylä

    2017-09-01

    Full Text Available Cancer cells are surrounded by a mechanically and biochemically distinct microenvironment that undergoes dynamic changes throughout the neoplastic progression. During this progression, some cancer cells acquire abnormal characteristics that potentiate their escape from the primary tumor site, to establish secondary tumors in distant organs. Recent studies with several human cancer cell lines have shown that the altered physical properties of tumor cells, such as their ability to apply high traction forces to the surroundings, are directly linked with their potential to invade and metastasize. To test the hypothetical interconnection between actomyosin-mediated traction forces and invasion potential within 3D-microenvironment, we utilized two canine mammary tumor cell lines with different contractile properties. These cell lines, canine mammary tumor (CMT-U27 and CMT-U309, were found to have distinct expression patterns of lineage-specific markers and organization of actin-based structures. In particular, CMT-U309 carcinoma cells were typified by thick contractile actomyosin bundles that exerted high forces to their environment, as measured by traction force microscopy. These high contractile forces also correlated with the prominent invasiveness of the CMT-U309 cell line. Furthermore, we found high contractility and 3D-invasion potential to be dependent on the activity of 5′AMP-activated protein kinase (AMPK, as blocking AMPK signaling was found to reverse both of these features. Taken together, our findings implicate that actomyosin forces correlate with the invasion potential of the studied cell lines.

  16. Relaxation-systolic pressure relation. A load-independent assessment of left ventricular contractility

    NARCIS (Netherlands)

    Gillebert, T. C.; Leite-Moreira, A. F.; de Hert, S. G.

    1997-01-01

    This contribution reviews the regulation of left ventricular pressure (LVP) fall by load and relates this regulation to left ventricular contractility. Load regulation of LVP fall has to be distinguished from neurohumoral regulation, from effects induced by arterial reflected waves and from

  17. Effects of Myocardial Contractility on Microemboli Production by Mechanical Heart Valves in a Bovine Model

    OpenAIRE

    Deklunder, Ghislaine; Lecroart, Jean-Louis; Conger, Jeff L.; Lapeyre, Didier; Gregoric, Igor; Rose, Harris; Tamez, Daniel; Frazier, O. H.

    2000-01-01

    Microemboli caused by mechanical heart valves have the potential to cause cerebrovascular events. We investigated the effects of myocardial contractility and heart rate on microemboli production in association with conventional and experimental mechanical heart valves implanted in the mitral position in a bovine model.

  18. Four days of muscle disuse impairs single fiber contractile function in young and old healthy men

    DEFF Research Database (Denmark)

    Hvid, Lars G; Suetta, Charlotte; Aagaard, Per

    2013-01-01

    The purpose of the study was to investigate the effects of 4days of disuse (knee brace) on contractile function of isolated vastus lateralis fibers (n=486) from 11 young (24.3±0.9yrs) and 11 old (67.2±1.0yrs) healthy men having comparable levels of physical activity. Prior to disuse single fiber...

  19. Transient impairments in single muscle fibre contractile function after prolonged cycling in elite endurance athletes

    DEFF Research Database (Denmark)

    Hvid, L G; Gejl, Kasper Degn; Bech, R D

    2013-01-01

    Prolonged muscle activity impairs whole-muscle performance and function. However, little is known about the effects of prolonged muscle activity on the contractile function of human single muscle fibres. The purpose of this study was to investigate the effects of prolonged exercise and subsequent...

  20. Chronic clenbuterol treatment compromises force production without directly altering skeletal muscle contractile machinery.

    Science.gov (United States)

    Py, G; Ramonatxo, C; Sirvent, P; Sanchez, A M J; Philippe, A G; Douillard, A; Galbès, O; Lionne, C; Bonnieu, A; Chopard, A; Cazorla, O; Lacampagne, A; Candau, R B

    2015-04-15

    Clenbuterol is a β2 -adrenergic receptor agonist known to induce skeletal muscle hypertrophy and a slow-to-fast phenotypic shift. The aim of the present study was to test the effects of chronic clenbuterol treatment on contractile efficiency and explore the underlying mechanisms, i.e. the muscle contractile machinery and calcium-handling ability. Forty-three 6-week-old male Wistar rats were randomly allocated to one of six groups that were treated with either subcutaneous equimolar doses of clenbuterol (4 mg kg(-1) day(-1) ) or saline solution for 9, 14 or 21 days. In addition to the muscle hypertrophy, although an 89% increase in absolute maximal tetanic force (Po ) was noted, specific maximal tetanic force (sPo) was unchanged or even depressed in the slow twitch muscle of the clenbuterol-treated rats (P clenbuterol treatment significantly reduced the rate constant of force development and the slow and fast rate constants of relaxation in extensor digitorum longus muscle (P clenbuterol-treated animals demonstrated decreased amplitude after 14 days (-19%, P clenbuterol treatment reduces contractile efficiency, with altered contraction and relaxation kinetics, but without directly altering the contractile machinery. Lower Ca(2+) release during contraction could partially explain these deleterious effects. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  1. Prolonged ischemic heart disease and coronary artery bypass - relation to contractile reserve

    DEFF Research Database (Denmark)

    Kofoed, Klaus F; Bangsgaard, Regitze; Carstensen, Steen

    2002-01-01

    OBJECTIVE: A major effect of coronary artery bypass grafting (CABG) in patients with ischemic heart disease and impaired left ventricular (LV) contractile function is believed to be an improvement in LV function due to recovery of dysfunctional, but viable myocardium. However, recent studies have...

  2. Spontaneous subcapsular and perirrenal hemorrhage

    International Nuclear Information System (INIS)

    Fuster, M.J.; Saez, J.; Perez-Paya, F.J.; Fernandez, F.

    1997-01-01

    To assess the role of CT in the etiologic diagnosis of spontaneous subcapsular and perirrenal hemorrhage. The CT findings are described in 13 patients presenting subcapsular and perirrenal hemorrhage. Those patients in whom the bleeding was not spontaneous were excluded. Surgical confirmation was obtained in nine cases. In 11 of the 13 cases (84.6%), involving five adenocarcinomas, five angiomyolipoma, two complicated cysts and one case of panarterities nodosa, CT disclosed the underlying pathology. In two cases (15.4%), it only revealed the extension of the hematoma, but gave no clue to its origin. CT is the technique of choice when spontaneous subcapsular and perirrenal hemorrhage is suspected since, in most cases, it reveals the underlying pathology. (Author)

  3. Characterization of the adenosine receptor in cultured embryonic chick atrial myocytes: Coupling to modulation of contractility and adenylate cyclase activity and identification by direct radioligand binding

    International Nuclear Information System (INIS)

    Liang, B.T.

    1989-01-01

    Adenosine receptors in a spontaneously contracting atrial myocyte culture from 14-day chick embryos were characterized by radioligand binding studies and by examining the involvement of G-protein in coupling these receptors to a high-affinity state and to the adenylate cyclase and the myocyte contractility. Binding of the antagonist radioligand [3H]-8-cyclopentyl-1,3-diproylxanthine ([3H]CPX) was rapid, reversible and saturable and was to a homogeneous population of sites with a Kd value of 2.1 +/- 0.2 nM and an apparent maximum binding of 26.2 +/- 3 fmol/mg of protein (n = 10, +/- S.E.). Guanyl-5-yl-(beta, gamma-imido)diphosphate had no effect on either the Kd or the maximum binding and CPX reversed the N6-R-phenyl-2-propyladenosine-induced inhibition of adenylate cyclase activity and contractility, indicating that [3H] CPX is an antagonist radioligand. Competition curves for [3H] CPX binding by a series of reference adenosine agonists were consistent with labeling of an A1 adenosine receptor and were better fit by a two-site model than by a one-site model. ADP-ribosylation of the G-protein by the endogenous NAD+ in the presence of pertussis toxin shifted the competition curves from bi to monophasic with Ki values similar to those of the KL observed in the absence of prior pertussis intoxication. The adenosine agonists were capable of inhibiting both the adenylate cyclase activity and myocyte contractility in either the absence or the presence of isoproterenol. The A1 adenosine receptor-selective antagonist CPX reversed these agonist effects. The order of ability of the reference adenosine receptor agonists in causing these inhibitory effects was similar to the order of potency of the same agonists in inhibiting the specific [3H]CPX binding (N6-R-phenyl-2-propyladenosine greater than N6-S-phenyl-2-propyladenosine or N-ethyladenosine-5'-uronic acid)

  4. Dynamic MR cholangiography after fatty meal loading. Cystic contractility and dynamic evaluation of biliary stasis

    International Nuclear Information System (INIS)

    Omata, Takayuki; Saito, Kazuhiro; Kotake, Fumio; Mizokami, Yuji; Matsuoka, Takeshi; Abe, Kimihiko

    2002-01-01

    Dynamic MR cholangiography was conducted on patients with cholelithiasis or choledocholithiasis who had consumed a fatty test meal (Molyork) and the cystic contractility and dynamics of biliary stasis was evaluated. The subjects were 25 with intracystic cholelithiasis, 10 with choledocholithiasis and 10 normal controls. For an imaging sequence, the rapid acquisition with relaxation enhancement (RARE) method was employed and imaging was conducted for 40 min (every 30 s following Molyork administration) without breath-holding. The gallbladder contraction ratio was computed and the contractile ratio for the common bile duct was calculated. To determine the bile flow to the duodenum, the high-intensity signal, indicating the flow from the lower common bile duct, and perfusion of the duodenum were observed in dynamic mode on the monitor with the naked eye and interpreted as positive bile flow. The frequency of this flow was visually monitored. The gallbladder contractile ratio was significantly reduced in patients with cholelithiasis or choledocholithiasis compared with the controls. In a comparison with the normal controls, no sequential changes were noted in the mean contractile ratio of the common bile duct of the patients with cholelithiasis or choledocholithiasis. The mean frequency of bile flow observed for each 40 min period was 13±2.4, 6±2.2, and 4±1.3 times for the controls, those with intracystic cholelithiasis, and those with choledocholithiasis, respectively. Compared with the controls, the latter two patient groups showed evident reductions in the frequency of bile flow to the duodenum (p<0.001). Dynamic MRC combined with Molyork loading makes it possible to compute cystic contractile ratios and perform a dynamic examination of bile flow under non-invasive, near-physiological conditions. (author)

  5. Esophagogastric junction contractile integral (EGJ-CI) quantifies changes in EGJ barrier function with surgical intervention.

    Science.gov (United States)

    Wang, D; Patel, A; Mello, M; Shriver, A; Gyawali, C P

    2016-05-01

    Esophagogastric junction contractile integral (EGJ-CI) assesses EGJ barrier function on esophageal high resolution manometry (HRM). We assessed EGJ-CI values in achalasia and gastroesophageal reflux disease (GERD) to determine if postoperative EGJ-CI changes reflected surgical intervention. Twenty-one achalasia patients (42.8 ± 3.2 years, 62% F) with HRM before and after Heller myotomy (HM) and 68 GERD patients (53.9 ± 1.8 years, 66% F) undergoing antireflux surgery (ARS) were compared to 21 healthy controls (27.6 ± 0.6 years, 52% F). Esophagogastric junction contractile integral (mmHg.cm) was calculated using the distal contractile integral measurement across the EGJ, measured above the gastric baseline and corrected for respiration. Pre and postsurgical EGJ-CI and conventional lower esophageal sphincter pressure (LESP) metrics were compared within and between these groups using non-parametric tests. Correlation between EGJ-CI and conventional LESP metrics was assessed. Baseline EGJ-CI was higher in achalasia compared to GERD (p integral declined by 59.2% after HM in achalasia (p = 0.001), and increased by 26.3% after ARS in GERD (p = 0.005). End-expiratory and basal LESP decreased by 74.5% and 64.5% with HM, but increased by only 17.8% and 4.3% with ARS. Differences were noted between Dor vs Toupet fundoplication in achalasia (p = 0.007), and partial vs complete ARS in GERD (p = 0.03). Esophagogastric junction contractile integral correlated modestly with both end-expiratory and basal LESP (Pearson's r of 0.8 for all), but was less robust in GERD (0.7). Esophagogastric junction contractile integral has clinical utility in assessing EGJ barrier function at baseline and after surgical intervention to the EGJ, and could complement conventional EGJ metrics. © 2016 John Wiley & Sons Ltd.

  6. Predicting changes in cardiac myocyte contractility during early drug discovery with in vitro assays

    Energy Technology Data Exchange (ETDEWEB)

    Morton, M.J., E-mail: michael.morton@astrazeneca.com [Discovery Sciences, AstraZeneca, Macclesfield, Cheshire SK10 4TG (United Kingdom); Armstrong, D.; Abi Gerges, N. [Drug Safety and Metabolism, AstraZeneca, Macclesfield, Cheshire SK10 4TG (United Kingdom); Bridgland-Taylor, M. [Discovery Sciences, AstraZeneca, Macclesfield, Cheshire SK10 4TG (United Kingdom); Pollard, C.E.; Bowes, J.; Valentin, J.-P. [Drug Safety and Metabolism, AstraZeneca, Macclesfield, Cheshire SK10 4TG (United Kingdom)

    2014-09-01

    Cardiovascular-related adverse drug effects are a major concern for the pharmaceutical industry. Activity of an investigational drug at the L-type calcium channel could manifest in a number of ways, including changes in cardiac contractility. The aim of this study was to define which of the two assay technologies – radioligand-binding or automated electrophysiology – was most predictive of contractility effects in an in vitro myocyte contractility assay. The activity of reference and proprietary compounds at the L-type calcium channel was measured by radioligand-binding assays, conventional patch-clamp, automated electrophysiology, and by measurement of contractility in canine isolated cardiac myocytes. Activity in the radioligand-binding assay at the L-type Ca channel phenylalkylamine binding site was most predictive of an inotropic effect in the canine cardiac myocyte assay. The sensitivity was 73%, specificity 83% and predictivity 78%. The radioligand-binding assay may be run at a single test concentration and potency estimated. The least predictive assay was automated electrophysiology which showed a significant bias when compared with other assay formats. Given the importance of the L-type calcium channel, not just in cardiac function, but also in other organ systems, a screening strategy emerges whereby single concentration ligand-binding can be performed early in the discovery process with sufficient predictivity, throughput and turnaround time to influence chemical design and address a significant safety-related liability, at relatively low cost. - Highlights: • The L-type calcium channel is a significant safety liability during drug discovery. • Radioligand-binding to the L-type calcium channel can be measured in vitro. • The assay can be run at a single test concentration as part of a screening cascade. • This measurement is highly predictive of changes in cardiac myocyte contractility.

  7. Dynamic MR cholangiography after fatty meal loading. Cystic contractility and dynamic evaluation of biliary stasis

    Energy Technology Data Exchange (ETDEWEB)

    Omata, Takayuki; Saito, Kazuhiro; Kotake, Fumio; Mizokami, Yuji; Matsuoka, Takeshi; Abe, Kimihiko [Tokyo Medical Coll., Ami, Ibaraki (Japan). Kasumigaura Hospital

    2002-07-01

    Dynamic MR cholangiography was conducted on patients with cholelithiasis or choledocholithiasis who had consumed a fatty test meal (Molyork) and the cystic contractility and dynamics of biliary stasis was evaluated. The subjects were 25 with intracystic cholelithiasis, 10 with choledocholithiasis and 10 normal controls. For an imaging sequence, the rapid acquisition with relaxation enhancement (RARE) method was employed and imaging was conducted for 40 min (every 30 s following Molyork administration) without breath-holding. The gallbladder contraction ratio was computed and the contractile ratio for the common bile duct was calculated. To determine the bile flow to the duodenum, the high-intensity signal, indicating the flow from the lower common bile duct, and perfusion of the duodenum were observed in dynamic mode on the monitor with the naked eye and interpreted as positive bile flow. The frequency of this flow was visually monitored. The gallbladder contractile ratio was significantly reduced in patients with cholelithiasis or choledocholithiasis compared with the controls. In a comparison with the normal controls, no sequential changes were noted in the mean contractile ratio of the common bile duct of the patients with cholelithiasis or choledocholithiasis. The mean frequency of bile flow observed for each 40 min period was 13{+-}2.4, 6{+-}2.2, and 4{+-}1.3 times for the controls, those with intracystic cholelithiasis, and those with choledocholithiasis, respectively. Compared with the controls, the latter two patient groups showed evident reductions in the frequency of bile flow to the duodenum (p<0.001). Dynamic MRC combined with Molyork loading makes it possible to compute cystic contractile ratios and perform a dynamic examination of bile flow under non-invasive, near-physiological conditions. (author)

  8. PKA catalytic subunit compartmentation regulates contractile and hypertrophic responses to β-adrenergic signaling

    Science.gov (United States)

    Yang, Jason H.; Polanowska-Grabowska, Renata K.; Smith, Jeffrey S.; Shields, Charles W.; Saucerman, Jeffrey J.

    2014-01-01

    β-adrenergic signaling is spatiotemporally heterogeneous in the cardiac myocyte, conferring exquisite control to sympathetic stimulation. Such heterogeneity drives the formation of protein kinase A (PKA) signaling microdomains, which regulate Ca2+ handling and contractility. Here, we test the hypothesis that the nucleus independently comprises a PKA signaling microdomain regulating myocyte hypertrophy. Spatially-targeted FRET reporters for PKA activity identified slower PKA activation and lower isoproterenol sensitivity in the nucleus (t50 = 10.60±0.68 min; EC50 = 89.00 nmol/L) than in the cytosol (t50 = 3.71±0.25 min; EC50 = 1.22 nmol/L). These differences were not explained by cAMP or AKAP-based compartmentation. A computational model of cytosolic and nuclear PKA activity was developed and predicted that differences in nuclear PKA dynamics and magnitude are regulated by slow PKA catalytic subunit diffusion, while differences in isoproterenol sensitivity are regulated by nuclear expression of protein kinase inhibitor (PKI). These were validated by FRET and immunofluorescence. The model also predicted differential phosphorylation of PKA substrates regulating cell contractility and hypertrophy. Ca2+ and cell hypertrophy measurements validated these predictions and identified higher isoproterenol sensitivity for contractile enhancements (EC50 = 1.84 nmol/L) over cell hypertrophy (EC50 = 85.88 nmol/L). Over-expression of spatially targeted PKA catalytic subunit to the cytosol or nucleus enhanced contractile and hypertrophic responses, respectively. We conclude that restricted PKA catalytic subunit diffusion is an important PKA compartmentation mechanism and the nucleus comprises a novel PKA signaling microdomain, insulating hypertrophic from contractile β-adrenergic signaling responses. PMID:24225179

  9. Right ventricle contractility during early postoperative period after coronary artery bypass grafting with cardiopulmonary bypass

    Directory of Open Access Journals (Sweden)

    А. Е. Баутин

    2015-10-01

    Full Text Available Emphasis in this research was placed on contractility of the right ventricle with regard to its relationship with systemic hemodynamics in patients undergoing coronary artery bypass grafting (CABG under cardiopulmonary bypass (CPB. The study included 25 patients (14 males, 11 females, mean age was 587 years admitted to ICU after CABG under CPB. All patients required inotropic therapy. The criterion for prescribing inotropic support in the postoperative period was a drop of the stroke volume index of the left ventricle below 35 ml/m 2 provided that the values of this indicator were normal before the perfusion period. Patients with previous pathology of the right ventricle or right coronary artery were excluded from the study. To evaluate the right ventricular function and systemic hemodynamics indicators, use was made of the PiCCO plus system and VoLEF addon device. It was found out that reduced contractility of the right ventricle may cause the reduction in stroke volume of the left ventricle with normal contractility. It was also observed that the increase of preload in patients with right ventricular ejection fraction less than 30% does not improve its function but leads to the increase of its end-diastolic volume. In 68% of cases, the need in inotropic agents in the early postoperative period after CABG was associated with the drop in right ventricle contractility, in 40% - with isolated right ven-tricular dysfunction. Patients with isolated reduction in right ventricle contractility required a longer period of inotropic support and ICU stay as compared with those with left ventricular failure.

  10. An Acanthamoeba castellanii metacaspase associates with the contractile vacuole and functions in osmoregulation.

    Science.gov (United States)

    Saheb, Entsar; Trzyna, Wendy; Bush, John

    2013-03-01

    Acanthamoeba castellanii is a free-living protozoan. Some strains are opportunistic pathogens. A type-I metacaspase was identified in A. castellanii (Acmcp) and was shown to be expressed through the encystation process. The model organism, Dictyostelium discoideum, has been used here as a model for studying these caspase-like proteins. Separate cell lines expressing a GFP-tagged version of the full length Acmcp protein, as well as a deletion proline region mutant of Acmcp protein (GFP-Acmcp-dpr), have been introduced into D. discoideum. Both mutants affect the cellular metabolism, characterized by an increase in the growth rate. Microscopic imaging revealed an association between Acmcp and the contractile vacuole system in D. discoideum. The treatment of cells with selected inhibitors in different environments added additional support to these findings. This evidence shows that Acmcp plays an important role in contractile vacuole regulation and mediated membrane trafficking in D. discoideum. Additionally, the severe defect in contractile vacuole function in GFP-Acmcp-dpr mutant cells suggests that the proline-rich region in Acmcp has an essential role in binding this protein with other partners to maintain this process. Furthermore, Yeast two-hybrid system identified there are weak interactions of the Dictyostelium contractile vacuolar proteins, including Calmodulin, RabD, Rab11 and vacuolar proton ATPase, with Acmcp protein. Taken together, our findings suggest that A. castellanii metacaspase associate with the contractile vacuole and have an essential role in cell osmoregulation, which contributes to its attractiveness as a possible target for treatment therapies against A. castellanii infection. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Effect of Agonist and Antagonist on the In Vitro Contractility of Inflamed Vermiform Appendix.

    Science.gov (United States)

    Singh, Phani Bhushan; Tiwary, Pushpakant; Singh, Sanjeev K; Pandey, Ratna; Roy, Atanu; Kar, Amrita Ghosh; Basu, Somprakas; Tiwari, Anil Kumar

    2017-06-01

    Appendicitis poses a great health problem worldwide. Previous studies demonstrated structural damage to neuronal network and interstitial cell of Cajal in appendicitis. Above observations suggest for the alterations in appendicular motility/contractility in appendicitis. But the mechanisms involved in mediating the contractility in inflamed vermiform appendix is not known till date. The present in vitro study was performed to find out the mechanisms responsible for contractility in the inflamed human vermiform appendix. Contractions of the longitudinal muscle strips of inflamed appendix were recorded in vitro at 37±0.5°C. Control contractions were recorded for 30 min after an initial tension of 0.5 gram. Initially dose-response experiments of agonists (acetylcholine, serotonin and histamine) were performed separately and the dose that produced maximum contraction was determined with each agonist. This maximal dose of agonist was used to elicit contractions in next series of experiments before and after pre-treatment with appropriate antagonists like atropine, ondansetron (5-HT 3 antagonist) and chlorpheniramine maleate respectively. Acetylcholine (ACh) and serotonin (5-HT) elicited maximum amplitude of contraction at 10 µM and 1 µM concentration respectively. These contractions were significantly blocked by prior exposure of muscle strips with atropine (100 µM) and ondansetron (10 µM). Histamine produced very low amplitude of contractions in comparison to ACh or 5-HT and did not exhibit dose-response relations. The histamine induced contractions were blocked by H 1 antagonist chlorpheniramine maleate (100 µM). The observations suggested that the contractility of longitudinal muscle strips of inflamed vermiform appendix in human beings was predominantly mediated by muscarinic and serotonergic (5-HT 3 ) mechanisms, whereas, histaminergic mechanisms played a minor role in mediating the contractility.

  12. Antihypertensive Effect of Syzygium cumini in Spontaneously Hypertensive Rats.

    Science.gov (United States)

    Ribeiro, Rachel Melo; Pinheiro Neto, Vicente Férrer; Ribeiro, Kllysmann Santos; Vieira, Denilson Amorim; Abreu, Iracelle Carvalho; Silva, Selma do Nascimento; Cartágenes, Maria do Socorro de Sousa; Freire, Sônia Maria de Farias; Borges, Antonio Carlos Romão; Borges, Marilene Oliveira da Rocha

    2014-01-01

    This study evaluated the in vivo potential antihypertensive effect of hydroalcoholic extract of Syzygium cumini leaves (HESC) in normotensive Wistar rats and in spontaneously hypertensive rats (SHR), as well as its in vitro effect on the vascular reactivity of resistance arteries. The hypotensive effect caused by intravenous infusion of HESC (0.01-4.0 mg/kg) in anesthetized Wistar rats was dose-dependent and was partially inhibited by pretreatment with atropine sulfate. SHR received HESC (0.5 g/kg/day), orally, for 8 weeks and mean arterial pressure, heart rate, and vascular reactivity were evaluated. Daily oral administration of HESC resulted in a time-dependent blood pressure reduction in SHR, with a maximum reduction of 62%. In the endothelium-deprived superior mesenteric arteries rings the treatment with HESC reduced by 40% the maximum effect (E max⁡) of contraction induced by NE. The contractile response to calcium and NE of endothelium-deprived mesenteric rings isolated from untreated SHR was reduced in a concentration-dependent manner by HESC (0.1, 0.25, and 0.5 mg/mL). This study demonstrated that Syzygium cumini reduces the blood pressure and heart rate of SHR and that this antihypertensive effect is probably due to the inhibition of arterial tone and extracellular calcium influx.

  13. Antihypertensive Effect of Syzygium cumini in Spontaneously Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Rachel Melo Ribeiro

    2014-01-01

    Full Text Available This study evaluated the in vivo potential antihypertensive effect of hydroalcoholic extract of Syzygium cumini leaves (HESC in normotensive Wistar rats and in spontaneously hypertensive rats (SHR, as well as its in vitro effect on the vascular reactivity of resistance arteries. The hypotensive effect caused by intravenous infusion of HESC (0.01–4.0 mg/kg in anesthetized Wistar rats was dose-dependent and was partially inhibited by pretreatment with atropine sulfate. SHR received HESC (0.5 g/kg/day, orally, for 8 weeks and mean arterial pressure, heart rate, and vascular reactivity were evaluated. Daily oral administration of HESC resulted in a time-dependent blood pressure reduction in SHR, with a maximum reduction of 62%. In the endothelium-deprived superior mesenteric arteries rings the treatment with HESC reduced by 40% the maximum effect (Emax⁡ of contraction induced by NE. The contractile response to calcium and NE of endothelium-deprived mesenteric rings isolated from untreated SHR was reduced in a concentration-dependent manner by HESC (0.1, 0.25, and 0.5 mg/mL. This study demonstrated that Syzygium cumini reduces the blood pressure and heart rate of SHR and that this antihypertensive effect is probably due to the inhibition of arterial tone and extracellular calcium influx.

  14. Spontaneous isolated celiac artery dissection

    Directory of Open Access Journals (Sweden)

    Tuba Cimilli Ozturk

    2011-01-01

    Full Text Available Dyspepsia with mild, stabbing epigastric discomfort without history of trauma is a very common symptom that emergency physicians see in their daily practice. Vascular emergencies, mostly the aortic dissection and aneurysm, are always described in the differential diagnosis with persistent symptoms. Isolated celiac artery dissection occurring spontaneously is a very rare diagnosis. The involvement of branch vessels is generally observed and patients show various clinical signs and symptoms according to the involved branch vessel. Here we are presenting a case with spontaneous isolated celiac artery dissection, without any branch vessel involvement or visceral damage, detected by computed tomography scans taken on admission.

  15. Spontaneous waves in muscle fibres

    Energy Technology Data Exchange (ETDEWEB)

    Guenther, Stefan; Kruse, Karsten [Department of Theoretical Physics, Saarland University, 66041 Saarbruecken (Germany); Max Planck Institute for the Physics of Complex Systems, Noethnitzer Street 38, 01187 Dresden (Germany)

    2007-11-15

    Mechanical oscillations are important for many cellular processes, e.g. the beating of cilia and flagella or the sensation of sound by hair cells. These dynamic states originate from spontaneous oscillations of molecular motors. A particularly clear example of such oscillations has been observed in muscle fibers under non-physiological conditions. In that case, motor oscillations lead to contraction waves along the fiber. By a macroscopic analysis of muscle fiber dynamics we find that the spontaneous waves involve non-hydrodynamic modes. A simple microscopic model of sarcomere dynamics highlights mechanical aspects of the motor dynamics and fits with the experimental observations.

  16. Human Papillomavirus Infection as a Possible Cause of Spontaneous Abortion and Spontaneous Preterm Delivery

    DEFF Research Database (Denmark)

    Ambühl, Lea Maria Margareta; Baandrup, Ulrik; Dybkær, Karen

    2016-01-01

    , and 10.9% (95% CI; 10.1–11.7) for umbilical cord blood. Summary estimates for HPV prevalence of spontaneous abortions and spontaneous preterm deliveries, in cervix (spontaneous abortions: 24.5%, and pretermdeliveries: 47%, resp.) and placenta (spontaneous abortions: 24.9%, and preterm deliveries: 50......%, resp.), were identified to be higher compared to normal full-term pregnancies (푃 spontaneous abortion, spontaneous preterm...

  17. Biventricular Pacing Cardiac Contractility Modulation Improves Cardiac Contractile Function via Upregulating SERCA2 and miR-133 in a Rabbit Model of Congestive Heart Failure

    Directory of Open Access Journals (Sweden)

    Bin Ning

    2014-05-01

    Full Text Available Objective: To compare the effects of biventricular electrical pacing and conventional single-ventricular pacing for cardiac contractility modulation (CCM on cardiac contractile function and to delineate the underlying molecular mechanisms. Methods: Forty rabbits were divided into four groups before surgery: healthy control, HF sham, HF left ventricular pacing CCM (LVP-CCM, and HF biventricular pacing CCM (BVP-CCM groups with n=10 for each group. A rabbit model of chronic heart failure was established by ligating ascending aortic root of rabbits. Then electrical stimulations during the absolute refractory period were delivered to the anterior wall of left ventricle in the LVP-CCM group and on the anterior wall of both left and right ventricles in the BVP-CCM group lasting six hours per day for seven days. Changes in ventricular structure, cardiac function and electrocardiogram were monitored before and after CCM stimulation. Results: Compared with the sham-operated group, heart weight, heart weight index, LV end-systolic diameter (LVESD, LV end-diastolic diameter (LVEDD in the LVP-CCM and BVP-CCM groups were significantly decreased (ppp2+-ATPase (SERCA2a protein levels were upregulated by 1.7 and 2.4 fold, along with simultaneous upregulation of a cardiac-enriched microRNA miR-133 levels by 2.6 and 3.3 fold, in LVP-CCM and BVP-CCM, respectively, compared to sham. Conclusions: Biventricular pacing CCM is superior to conventional monoventricular pacing CCM, producing greater improvement cardiac contractile function. Greater upregulation of SERCA2 and miR-133 may account, at least partially, for the improvement by BVP-CCM.

  18. Spontaneous emission by moving atoms

    International Nuclear Information System (INIS)

    Meystre, P.; Wilkens, M.

    1994-01-01

    It is well known that spontaneous emission is not an intrinsic atomic property, but rather results from the coupling of the atom to the vacuum modes of the electromagnetic field. As such, it can be modified by tailoring the electromagnetic environment into which the atom can radiate. This was already realized by Purcell, who noted that the spontaneous emission rate can be enhanced if the atom placed inside a cavity is resonant with one of the cavity is resonant with one of the cavity modes, and by Kleppner, who discussed the opposite case of inhibited spontaneous emission. It has also been recognized that spontaneous emission need not be an irreversible process. Indeed, a system consisting of a single atom coupled to a single mode of the electromagnetic field undergoes a periodic exchange of excitation between the atom and the field. This periodic exchange remains dominant as long as the strength of the coupling between the atom and a cavity mode is itself dominant. 23 refs., 6 figs

  19. Spontaneous Development of Moral Concepts

    Science.gov (United States)

    Siegal, M.

    1975-01-01

    Moral competence is more difficult to attain than scientific competence. Since language comprehension plays a central role in conceptual development, and moral language is difficult to learn, there is a common deficiency in moral conceptual development. This suggests a theory of non-spontaneous solutions to moral problems. (Author/MS)

  20. Shell theorem for spontaneous emission

    DEFF Research Database (Denmark)

    Kristensen, Philip Trøst; Mortensen, Jakob Egeberg; Lodahl, Peter

    2013-01-01

    and therefore is given exactly by the dipole approximation theory. This surprising result is a spontaneous emission counterpart to the shell theorems of classical mechanics and electrostatics and provides insights into the physics of mesoscopic emitters as well as great simplifications in practical calculations....

  1. Prediction of Spontaneous Preterm Birth

    NARCIS (Netherlands)

    Dijkstra, Karolien

    2002-01-01

    Preterm birth is a leading cause of neonatal morbidity and mortality. It is a major goal in obstetrics to lower the incidence of spontaneous preterm birth (SPB) and related neonatal morbidity and mortality. One of the principal objectives is to discover early markers that would allow us to identify

  2. EAMJ Dec. Spontaneous.indd

    African Journals Online (AJOL)

    2008-12-12

    Dec 12, 2008 ... surgical abortion at one month gestation without any complication. The second pregnancy which was a year prior resulted in a spontaneous miscarriage at two months followed by evacuation of retained products of conception with no post abortion complications. Antibiotics were taken following both.

  3. Spontaneous fission of superheavy nuclei

    Indian Academy of Sciences (India)

    the Yukawa-plus-exponential potential. The microscopic shell and pairing corrections are obtained using the Strutinsky and BCS approaches and the cranking formulae yield the inertia tensor. Finally, the WKB method is used to calculate penetrabilities and spontaneous fission half-lives. Calculations are performed for the ...

  4. Spontaneous Retropharyngeal Emphysema: A Case Report | Chi ...

    African Journals Online (AJOL)

    ... is a rare clinical condition in pediatric otolaryngology. The predominant symptoms are sore throat, odynophagia, dysphagia, and neck pain. Here, we report a case of spontaneous retropharyngeal emphysema. Keywords: Iatrogenic injury, retropharyngeal emphysema, spontaneous retropharyngeal emphysem, trauma ...

  5. La maladie de Grisel : Spontaneous atlantoaxial subluxation

    NARCIS (Netherlands)

    Meek, MF; Robinson, PH; Hermens, RAEC

    Objective: "La maladie de Grisel" (Grisel's syndrome) is a spontaneously occurring atlantoaxial subluxation with torticollis. We present a case of atlantoaxial subluxation occurring in a 20-year period of pharyngoplasty surgery. The occurrence of a "spontaneous" atlantoaxial subluxation after oral

  6. Measuring the Contractile Response of Isolated Tissue Using an Image Sensor

    Directory of Open Access Journals (Sweden)

    David Díaz-Martín

    2015-04-01

    Full Text Available Isometric or isotonic transducers have traditionally been used to study the contractile/relaxation effects of drugs on isolated tissues. However, these mechanical sensors are expensive and delicate, and they are associated with certain disadvantages when performing experiments in the laboratory. In this paper, a method that uses an image sensor to measure the contractile effect of drugs on blood vessel rings and other luminal organs is presented. The new method is based on an image-processing algorithm, and it provides a fast, easy and non-expensive way to analyze the effects of such drugs. In our tests, we have obtained dose-response curves from rat aorta rings that are equivalent to those achieved with classical mechanic sensors.

  7. Effect of a crude sulfated polysaccharide from Halymenia floresia (Rhodophyta on gastrointestinal smooth muscle contractility

    Directory of Open Access Journals (Sweden)

    José Ronaldo Vasconcelos Graça

    2011-10-01

    Full Text Available The aim of this work was to study the effect of Halymenia floresia (Hf on duodenum contractility, and on experimental protocols of gastric compliance (GC in rats. Fraction Hf2s exhibited a concentration-dependent myocontractile effect (EC50 12.48 µg/ml, and an inhibitory effect after consecutive washing. The contractile response promoted by Hf2s in the duodenum strips was completely inhibited by verapamil, and the effects were prevented in the presence of Ca2+-free medium. The pretreatment with atropine prevented the Hf2s myocontractile effect. Hf2s was also capable to decrease the GC (from 3.8±0.06 to 3.4±0.13 ml, P<0.05, which did not return to basal levels after more 50 min of observation. These results indicated that the algal polysaccharide possessed in vitro and in vivo gastrointestinal effects.

  8. Pharmacology of Casimiroa edulis; III. Relaxant and contractile effects in rat aortic rings.

    Science.gov (United States)

    Magos, G A; Vidrio, H; Enríquez, R

    1995-06-23

    The relaxant and contractile effects of an aqueous extract of the seeds of the hypotensive plant Casimiroa edulis were investigated in rat aortic rings. The extract inhibited contractions elicited by noradrenaline, serotonin and prostaglandin F2 alpha, but did not affect responses to KCl. Inhibition did not require the presence of intact vascular endothelium and was not affected by histamine antagonists. In this preparation, the extract also elicited concentration-related contractions which were more marked in the absence of endothelium, were not blocked by histamine antagonists, and were completely suppressed by alpha-adrenergic blockade. It was concluded that the relaxant effect of the extract is not exerted through release of an endothelial relaxing factor nor through blockade of calcium channels or of specific smooth muscle receptors, and does not involve histaminergic mechanisms. The contractile effect is modulated by vascular endothelium and is alpha-adrenergic in nature.

  9. Effects of ageing on single muscle fibre contractile function following short-term immobilisation

    DEFF Research Database (Denmark)

    Hvid, Lars G; Ortenblad, Niels; Aagaard, Per

    2011-01-01

    Very little attention has been given to the combined effects of healthy ageing and short-term disuse on the contractile function of human single muscle fibres. Therefore, the present study investigated the effects of 2 weeks of lower limb cast immobilisation (i.e. disuse) on selected contractile.......05), respectively. In conclusion, 2 weeks of lower limb immobilisation caused greater impairments in single muscle fibre force and specific force in MHC IIa than MHC I fibres independently of age. In contrast, immobilisation-induced changes in Ca(2+) sensitivity that were dependent on age and MHC isoform....... properties of single muscle fibres (n = 378) from vastus lateralis of nine young (24 ± 1 years) and eight old (67 ± 2 years) healthy men with comparable levels of physical activity. Prior to immobilisation, MHC IIa fibres produced higher maximum Ca(2+)-activated force (approx. 32%) and specific force (approx...

  10. Effect of changes in contractility on the index of myocardial performance in the dysfunctional left ventricle

    Directory of Open Access Journals (Sweden)

    Lavine Steven J

    2006-11-01

    Full Text Available Abstract Background The index of myocardial performance has prognostic power in patients with cardiomyopathy and following myocardial infarction. As the index of myocardial performance has been shown to be preload and afterload dependent, the effect of altering contractility on IMP and its components with left ventricular dysfunction has been incompletely delineated. Methods Chronic left ventricular dysfunction was induced in 10 canines using coronary microsphere embolization. Each dog was instrumented and imaged with 2D echo and Doppler. At the same atrially paced rate, contractility was increased with a dobutamine infusion and then following 4 weeks of oral digoxin. Results With chronic left ventricular dysfunction, a reduced left ventricular ejection fraction (42 ± 3%, p Conclusion Increased inotropy with digoxin and dobutamine reduced the index of myocardial performance in dogs with left ventricular dysfunction. Shortened isovolumic contraction time, increased diastolic filling period, and reduced left ventricular end diastolic pressure with digoxin may provide insight into its efficacy in heart failure.

  11. Contractile responses to ergotamine and dihydroergotamine in the perfused middle cerebral artery of rat

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Peer; Nilsson, Elisabeth; Edvinsson, Lars

    2007-01-01

    , with pEC(50) values of 7.6+/-0.2 for ergotamine and 8.4+/-0.5 for DHE. The responses were blocked by the 5-HT(2A) receptor antagonist ketanserin (concentration 10(-12) to 10(-5) M) and partially with the 5-HT(1B) receptor antagonist BRL-11557PM-B. The 5-HT(1D) receptor antagonist SB-224289-A had...... no significant effect. Using a myograph technique, isolated ring segments of the MCA with intact endothelium were mounted on two metal wires. Neither agonist caused relaxation of resting vessels, however, they both responded by weak contractile responses (26+/-3% of submaximal contractile capacity relative to 60...

  12. A computerized experimental set-up for in vitro evaluation of smooth muscle contractility.

    Science.gov (United States)

    Das, J; Vereecken, R L; Schellemans, D

    1986-12-01

    A fully automated system is designed and developed for the investigation of in vitro contractility of muscle tissue in response to dose-dependent pharmacologic and/or electrical stimulation. The heart of the set-up is a personal technical computer. It drives the experiment by selecting and changing drug concentrations, by applying electrical stimulation, by sampling the tissue's contractile response and by real-time calculation of results. Parameters of interest are derived and updated for further selection and statistical manipulation. Alpha-numerical or graphical hardcopies may be drawn at any time. Investigator's intervention is limited to preparing perfusing solutions, mounting the muscle tissue strips, deciding test condition parameters, supervising the experimental progress and leading statistical calculations.

  13. Numerical investigation of perforated polymer microcantilever sensor for contractile behavior of cardiomyocytes

    Science.gov (United States)

    Khoa Nguyen, Trieu; Lee, Dong-Weon; Lee, Bong-Kee

    2017-06-01

    In this study, a numerical investigation of microcantilever sensors for detecting the contractile behavior of cardiomyocytes (CMs) was performed. Recently, a novel surface-patterned perforated SU-8 microcantilever sensor has been developed for the preliminary screening of cardiac toxicity. From the contractile motion of the CMs cultured on the microcantilever surface, a macroscopic bending of the microcantilever was obtained, which is considered to reflect a physiological change. As a continuation of the previous research, a novel numerical method based on a surface traction model was proposed and verified to further understand the bending behavior of the microcantilevers. Effects of various factors, including surface traction magnitude, focal area of CMs, and stiffness of microcantilever, on the bending displacement were investigated. From static and transient analyses, the focal area was found to be the most crucial factor. In addition, the current result can provide a design guideline for various micromechanical devices based on the same principle.

  14. Slow force response and auto-regulation of contractility in heterogeneous myocardium.

    Science.gov (United States)

    Markhasin, Vladimir S; Balakin, Alexander A; Katsnelson, Leonid B; Konovalov, Pavel; Lookin, Oleg N; Protsenko, Yuri; Solovyova, Olga

    2012-01-01

    Classically, the slow force response (SFR) of myocardium refers to slowly developing changes in cardiac muscle contractility induced by external mechanical stimuli, e.g. sustained stretch. We present evidence for an intra-myocardial SFR (SFR(IM)), caused by the internal mechanical interactions of muscle segments in heterogeneous myocardium. Here we study isometric contractions of a pair of end-to-end connected functionally heterogeneous cardiac muscles (an in-series muscle duplex). Duplex elements can be either biological muscles (BM), virtual muscles (VM), or a hybrid combination of BM and VM. The VM implements an Ekaterinburg-Oxford mathematical model accounting for the ionic and myofilament mechanisms of excitation-contraction coupling in cardiomyocytes. SFR(IM) is expressed in gradual changes in the overall duplex force and in the individual contractility of each muscle, induced by cyclic auxotonic deformations of coupled muscles. The muscle that undergoes predominant cyclic shortening shows force enhancement upon return to its isometric state in isolation, whereas average cyclic lengthening may decrease the individual muscle contractility. The mechanical responses are accompanied with slow and opposite changes in the shape and duration of both the action potential and Ca²⁺ transient in the cardiomyocytes of interacting muscles. Using the mathematical model we found that the contractility changes in interacting muscles follow the alterations in the sarcoplasmic reticulum loading in cardiomyocytes which result from the length-dependent Ca²⁺ activation of myofilaments and intracellular mechano-electrical feedback. The SFR(IM) phenomena unravel an important mechanism of cardiac functional auto-regulation applicable to the heart in norm and pathology, especially to hearts with severe electrical and/or mechanical dyssynchrony. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Intestine of dystrophic mice presents enhanced contractile resistance to stretching despite morphological impairment

    OpenAIRE

    Alves, Gabriel A. [UNIFESP; Silva, Luisa R. [UNIFESP; Rosa, Eloi F. [UNIFESP; Aboulafia, Jeannine [UNIFESP; Freymueller-Haapalainen, Edna [UNIFESP; Souccar, Caden [UNIFESP; Nouailhetas, Viviane L. A. [UNIFESP

    2014-01-01

    Protein dystrophin is a component of the dystrophin-associated protein complex, which links the contractile machinery to the plasma membrane and to the extra-cellular matrix. Its absence leads to a condition known as Duchenne muscular dystrophy (DMD), a disease characterized by progressive skeletal muscle degeneration, motor disability, and early death. in mdx mice, the most common DMD animal model, loss of muscle cells is observed, but the overall disease alterations are less intense than in...

  16. Cardiac-Specific Overexpression of Catalase Attenuates Lipopolysaccharide-Induced Myocardial Contractile Dysfunction: Role of Autophagy

    Science.gov (United States)

    Turdi, Subat; Han, Xuefeng; Huff, Anna F.; Roe, Nathan D.; Hu, Nan; Gao, Feng; Ren, Jun

    2012-01-01

    Lipopolysaccharide (LPS) from Gram-negative bacteria is a major initiator of sepsis, leading to cardiovascular collapse. Accumulating evidence has indicated a role of reactive oxygen species (ROS) in cardiovascular complication in sepsis. This study was designed to examine the effect of cardiac-specific overexpression of catalase in LPS-induced cardiac contractile dysfunction and the underlying mechanism(s) with a focus on autophagy. Catalase transgenic and wild-type FVB mice were challenged with LPS (6 mg/kg) and cardiac function was evaluated. Levels of oxidative stress, autophagy, apoptosis and protein damage were examined using fluorescence microscopy, Western blot, TUNEL assay, caspase-3 activity and carbonyl formation. Kaplan-Meier curve was constructed for survival following LPS treatment. Our results revealed a lower mortality in catalase mice compared with FVB mice following LPS challenge. LPS injection led to depressed cardiac contractile capacity as evidenced by echocardiography and cardiomyocyte contractile function, the effect of which was ablated by catalase overexpression. LPS treatment induced elevated TNF-α level, autophagy, apoptosis (TUNEL, caspase-3 activation, cleaved caspase-3), production of ROS and O2−, and protein carbonyl formation, the effects of which were significantly attenuated by catalase overexpression. Electron microscopy revealed focal myocardial damage characterized by mitochondrial injury following LPS treatment, which was less severe in catalase mice. Interestingly, LPS-induced cardiomyocyte contractile dysfunction was prevented by antioxidant NAC and the autophagy inhibitor 3-methyladenine. Taken together, our data revealed that catalase protects against LPS-induced cardiac dysfunction and mortality, which may be associated with inhibition of oxidative stress and autophagy. PMID:22902401

  17. Cardiac-specific overexpression of catalase attenuates lipopolysaccharide-induced myocardial contractile dysfunction: role of autophagy.

    Science.gov (United States)

    Turdi, Subat; Han, Xuefeng; Huff, Anna F; Roe, Nathan D; Hu, Nan; Gao, Feng; Ren, Jun

    2012-09-15

    Lipopolysaccharide (LPS) from gram-negative bacteria is a major initiator of sepsis, leading to cardiovascular collapse. Accumulating evidence has indicated a role of reactive oxygen species (ROS) in cardiovascular complications in sepsis. This study was designed to examine the effect of cardiac-specific overexpression of catalase in LPS-induced cardiac contractile dysfunction and the underlying mechanism(s) with a focus on autophagy. Catalase transgenic and wild-type FVB mice were challenged with LPS (6 mg/kg) and cardiac function was evaluated. Levels of oxidative stress, autophagy, apoptosis, and protein damage were examined using fluorescence microscopy, Western blot, TUNEL assay, caspase-3 activity, and carbonyl formation. A Kaplan-Meier curve was constructed for survival after LPS treatment. Our results revealed a lower mortality in catalase mice compared with FVB mice after LPS challenge. LPS injection led to depressed cardiac contractile capacity as evidenced by echocardiography and cardiomyocyte contractile function, the effect of which was ablated by catalase overexpression. LPS treatment induced elevated TNF-α level, autophagy, apoptosis (TUNEL, caspase-3 activation, cleaved caspase-3), production of ROS and O(2)(-), and protein carbonyl formation, the effects of which were significantly attenuated by catalase overexpression. Electron microscopy revealed focal myocardial damage characterized by mitochondrial injury after LPS treatment, which was less severe in catalase mice. Interestingly, LPS-induced cardiomyocyte contractile dysfunction was prevented by the antioxidant N-acetylcysteine and the autophagy inhibitor 3-methyladenine. Taken together, our data revealed that catalase protects against LPS-induced cardiac dysfunction and mortality, which may be associated with inhibition of oxidative stress and autophagy. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Cardiac-Specific Overexpression of Catalase Attenuates Lipopolysaccharide-Induced Myocardial Contractile Dysfunction: Role of Autophagy

    OpenAIRE

    Turdi, Subat; Han, Xuefeng; Huff, Anna F.; Roe, Nathan D.; Hu, Nan; Gao, Feng; Ren, Jun

    2012-01-01

    Lipopolysaccharide (LPS) from Gram-negative bacteria is a major initiator of sepsis, leading to cardiovascular collapse. Accumulating evidence has indicated a role of reactive oxygen species (ROS) in cardiovascular complication in sepsis. This study was designed to examine the effect of cardiac-specific overexpression of catalase in LPS-induced cardiac contractile dysfunction and the underlying mechanism(s) with a focus on autophagy. Catalase transgenic and wild-type FVB mice were challenged ...

  19. Myosin phosphorylation improves contractile economy of mouse fast skeletal muscle during staircase potentiation.

    Science.gov (United States)

    Bunda, Jordan; Gittings, William; Vandenboom, Rene

    2018-01-30

    Phosphorylation of the myosin regulatory light chain (RLC) by skeletal myosin light chain kinase (skMLCK) potentiates rodent fast twitch muscle but is an ATP-requiring process. Our objective was to investigate the effect of skMLCK-catalyzed RLC phosphorylation on the energetic cost of contraction and the contractile economy (ratio of mechanical output to metabolic input) of mouse fast twitch muscle in vitro (25°C). To this end, extensor digitorum longus (EDL) muscles from wild-type (WT) and from skMLCK-devoid (skMLCK -/- ) mice were subjected to repetitive low-frequency stimulation (10 Hz for 15 s) to produce staircase potentiation of isometric twitch force, after which muscles were quick frozen for determination of high-energy phosphate consumption (HEPC). During stimulation, WT muscles displayed significant potentiation of isometric twitch force while skMLCK -/- muscles did not (i.e. 23% versus 5% change, respectively). Consistent with this, RLC phosphorylation was increased ∼3.5-fold from the unstimulated control value in WT but not in skMLCK -/- muscles. Despite these differences, the HEPC of WT muscles was not greater than that of skMLCK -/- muscles. As a result of the increased contractile output relative to HEPC, the calculated contractile economy of WT muscles was greater than that of skMLCK -/- muscles. Thus, our results suggest that skMLCK-catalyzed phosphorylation of the myosin RLC increases the contractile economy of WT mouse EDL muscle compared with skMLCK -/- muscles without RLC phosphorylation. © 2018. Published by The Company of Biologists Ltd.

  20. Robust gap repair in the contractile ring ensures timely completion of cytokinesis.

    OpenAIRE

    Silva, AM; Osório, DS; Pereira, AJ; Maiato, H; Pinto, IM; Rubinstein, B; Gassmann, R; Telley, IA; Carvalho, AX

    2016-01-01

    Cytokinesis in animal cells requires the constriction of an actomyosin contractile ring, whose architecture and mechanism remain poorly understood. We use laser microsurgery to explore the biophysical properties of constricting rings in Caenorhabditis elegans embryos. Laser cutting causes rings to snap open. However, instead of disintegrating, ring topology recovers and constriction proceeds. In response to severing, a finite gap forms and is repaired by recruitment of new material in an acti...

  1. The Effects of Histamine H3 Receptors on Contractile Responses on Rat Gastric Fundus

    OpenAIRE

    Aşkın Hekimoğlu; Ramazan Çiçek

    2006-01-01

    The aim of this study is to determine the effects of histamine receptors on the gastrointestinal system smooth muscle contractions and the role of histamine H3 receptors on these effects. İsolated rat gastric fundus preparations were hanged on isolated organ bath and histamine receptor agonist and anthagonists were added to the bath solution and the electrical field stimulation-induced contractile responses were evaluated. In our study groups after blocking one of the histamine receptor...

  2. Systematics of spontaneous positron lines

    International Nuclear Information System (INIS)

    Mueller, U.; Reus, T. de; Reinhardt, J.; Mueller, B.; Greiner, W.

    1985-08-01

    Dynamical and spontaneous positron emission are investigated for heavy-ion collisions with long time delay using a semiclassical description. Numerical results and analytical expressions for the characteristic quantities of the resulting spontaneous positron line, i.e., its position, width, and cross section, are compared. The expected behaviour of the line position and cross section and its visibility against the spectrum of dynamically created positrons is discussed in dependence of the united charge Zsub(u) of projectile and target nucleus in a range of systems from Zsub(u)=180 up to Zsub(u)=188. The results are confronted with presently available experimental data, and possible implications on further experiments are worked out. (orig.)

  3. Spontaneous Rotational Inversion in Phycomyces

    KAUST Repository

    Goriely, Alain

    2011-03-01

    The filamentary fungus Phycomyces blakesleeanus undergoes a series of remarkable transitions during aerial growth. During what is known as the stagea IV growth phase, the fungus extends while rotating in a counterclockwise manner when viewed from above (stagea IVa) and then, while continuing to grow, spontaneously reverses to a clockwise rotation (stagea IVb). This phase lasts for 24-48Ah and is sometimes followed by yet another reversal (stageAIVc) before the overall growth ends. Here, we propose a continuum mechanical model of this entire process using nonlinear, anisotropic, elasticity and show how helical anisotropy associated with the cell wall structure can induce spontaneous rotation and, under appropriate circumstances, the observed reversal of rotational handedness. © 2011 American Physical Society.

  4. Spontaneous regression of colon cancer.

    Science.gov (United States)

    Kihara, Kyoichi; Fujita, Shin; Ohshiro, Taihei; Yamamoto, Seiichiro; Sekine, Shigeki

    2015-01-01

    A case of spontaneous regression of transverse colon cancer is reported. A 64-year-old man was diagnosed as having cancer of the transverse colon at a local hospital. Initial and second colonoscopy examinations revealed a typical cancer of the transverse colon, which was diagnosed as moderately differentiated adenocarcinoma. The patient underwent right hemicolectomy 6 weeks after the initial colonoscopy. The resected specimen showed only a scar at the tumor site, and no cancerous tissue was proven histologically. The patient is alive with no evidence of recurrence 1 year after surgery. Although an antitumor immune response is the most likely explanation, the exact nature of the phenomenon was unclear. We describe this rare case and review the literature pertaining to spontaneous regression of colorectal cancer. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Management of intractable spontaneous epistaxis

    Science.gov (United States)

    Rudmik, Luke

    2012-01-01

    Background: Epistaxis is a common otolaryngology emergency and is often controlled with first-line interventions such as cautery, hemostatic agents, or anterior nasal packing. A subset of patients will continue to bleed and require more aggressive therapy. Methods: Intractable spontaneous epistaxis was traditionally managed with posterior nasal packing and prolonged hospital admission. In an effort to reduce patient morbidity and shorten hospital stay, surgical and endovascular techniques have gained popularity. A literature review was conducted. Results: Transnasal endoscopic sphenopalatine artery ligation and arterial embolization provide excellent control rates but the decision to choose one over the other can be challenging. The role of transnasal endoscopic anterior ethmoid artery ligation is unclear but may be considered in certain cases when bleeding localizes to the ethmoid region. Conclusion: This article will focus on the management of intractable spontaneous epistaxis and discuss the role of endoscopic arterial ligation and embolization as it pertains to this challenging clinical scenario. PMID:22391084

  6. Cellular contractility and substrate elasticity: a numerical investigation of the actin cytoskeleton and cell adhesion.

    Science.gov (United States)

    Ronan, William; Deshpande, Vikram S; McMeeking, Robert M; McGarry, J Patrick

    2014-04-01

    Numerous experimental studies have established that cells can sense the stiffness of underlying substrates and have quantified the effect of substrate stiffness on stress fibre formation, focal adhesion area, cell traction, and cell shape. In order to capture such behaviour, the current study couples a mixed mode thermodynamic and mechanical framework that predicts focal adhesion formation and growth with a material model that predicts stress fibre formation, contractility, and dissociation in a fully 3D implementation. Simulations reveal that SF contractility plays a critical role in the substrate-dependent response of cells. Compliant substrates do not provide sufficient tension for stress fibre persistence, causing dissociation of stress fibres and lower focal adhesion formation. In contrast, cells on stiffer substrates are predicted to contain large amounts of dominant stress fibres. Different levels of cellular contractility representative of different cell phenotypes are found to alter the range of substrate stiffness that cause the most significant changes in stress fibre and focal adhesion formation. Furthermore, stress fibre and focal adhesion formation evolve as a cell spreads on a substrate and leading to the formation of bands of fibres leading from the cell periphery over the nucleus. Inhibiting the formation of FAs during cell spreading is found to limit stress fibre formation. The predictions of this mutually dependent material-interface framework are strongly supported by experimental observations of cells adhered to elastic substrates and offer insight into the inter-dependent biomechanical processes regulating stress fibre and focal adhesion formation.

  7. Changes of contractile responses due to simulated weightlessness in rat soleus muscle

    Science.gov (United States)

    Elkhammari, A.; Noireaud, J.; Léoty, C.

    1994-08-01

    Some contractile and electrophysiological properties of muscle fibers isolated from the slow-twitch soleus (SOL) and fast-twitch extensor digitorum longus (EDL) muscles of rats were compared with those measured in SOL muscles from suspended rats. In suspendede SOL (21 days of tail-suspension) membrane potential (Em), intracellular sodium activity (aiNa) and the slope of the relationship between Em and log [K]o were typical of fast-twitch muscles. The relation between the maximal amplitude of K-contractures vs Em was steeper for control SOL than for EDL and suspended SOL muscles. After suspension, in SOL muscles the contractile threshold and the inactivation curves for K-contractures were shifted to more positive Em. Repriming of K-contractures was unaffected by suspencion. The exposure of isolated fibers to perchlorate (ClO4-)-containing (6-40 mM) solutions resulted ina similar concentration-dependent shift to more negative Em of activation curves for EDL and suspended SOL muscles. On exposure to a Na-free TEA solution, SOL from control and suspended rats, in contrast to EDL muscles, generated slow contractile responses. Suspended SOL showed a reduced sensitivity to the contracture-producing effect of caffeine compared to control muscles. These results suggested that the modification observed due to suspension could be encounted by changes in the characteristics of muscle fibers from slow to fast-twitch type.

  8. Combination Therapy Comprising a Static Magnetic Field with Contractility Improves Skin Wounds.

    Science.gov (United States)

    Song, Byeong-Wook; Hong, Hyunki; Jung, Yu Jin; Lee, Ju Hyung; Kim, Bong-Soo; Lee, Hoon-Bum

    2018-03-21

    Cutaneous wounds can present significant clinical problems because of abnormal healing after deep dermal damage. Despite technical advances in wound care, there are still unmet needs that result from inefficient treatment. In this study, we aimed to improve skin wound healing using a contractibility band with static magnetic field (SMF), termed a Magnetic band (Mb). To examine the effect of the Mb on wound healing, full-thickness 15 mm × 35 mm excision wounds were surgically created on the dorsum of rats. An elastic and contractile band (non-treatment), or one neodymium magnet (Nd-1) or two magnets with an elastic and contractile band (Nd-2) were topically applied to the wound daily and the wound size was measured from day 1 to 7 after surgery. Nd-2 showed a significant (95%) reduction in the wound size at day 3. Histological analysis showed that pro-inflammatory cytokine levels were diminished by Nd-2, and granulation tissue and microvessels were increased compared with those in the sham group. During Mb-induced wound healing, apoptosis was significantly reduced and matrix remodeling-related factors were initially regulated. The results suggest that combination therapy comprising an SMF and an elastic and contractile band could be a promising tool to heal cutaneous wounds rapidly.

  9. Impact of tamsulosin and nifedipine on contractility of pregnant rat ureters in vitro.

    Science.gov (United States)

    Haddad, Lisette; Corriveau, Stéphanie; Rousseau, Eric; Blouin, Simon; Pasquier, Jean-Charles; Ponsot, Yves; Roy-Lacroix, Marie-Ève

    2018-01-01

    To evaluate the in vitro effect of tamsulosin and nifedipine on the contractility of pregnant rat ureters and to perform quantitative analysis of the pharmacological effects. Medical expulsive therapy (MET) is commonly used to treat urolithiasis. However, this treatment is seldom used in pregnant women since no studies support this practice. This was an in vitro study on animal tissue derived from pregnant Sprague-Dawley rats. A total of 124 ureteral segments were mounted in an organ bath system and contractile response to methacholine (MCh) was assessed. Tamsulosin or nifedipine were added at cumulative concentrations (0.001-1 μM). The area under the curve (AUC) from isometric tension measurements was calculated. The effect of pharmacological agents and the respective controls were assessed by calculating the AUC for each 5-min interval. Statistical analyses were performed using the Mann-Whitney-Wilcoxon nonparametric test. Both drugs displayed statistically significant inhibitory activity at concentrations of 0.1 and 1 μM for tamsulosin and 1 μM for nifedipine when calculated as the AUC as compared to DMSO controls. Tamsulosin and nifedipine directly inhibit MCh-induced contractility of pregnant rat ureters. Further work is needed to determine the clinical efficacy of these medications for MET in pregnancy.

  10. Improvement of diaphragm and limb muscle isotonic contractile performance by K+ channel blockade

    Directory of Open Access Journals (Sweden)

    Pollarine Jennifer

    2010-01-01

    Full Text Available Abstract The K+ channel blocking aminopyridines greatly improve skeletal muscle isometric contractile performance during low to intermediate stimulation frequencies, making them potentially useful as inotropic agents for functional neuromuscular stimulation applications. Most restorative applications involve muscle shortening; however, previous studies on the effects of aminopyridines have involved muscle being held at constant length. Isotonic contractions differ substantially from isometric contractions at a cellular level with regards to factors such as cross-bridge formation and energetic requirements. The present study tested effects of 3,4-diaminopyridine (DAP on isotonic contractile performance of diaphragm, extensor digitorum longus (EDL and soleus muscles from rats. During contractions elicited during 20 Hz stimulation, DAP improved work over a range of loads for all three muscles. In contrast, peak power was augmented for the diaphragm and EDL but not the soleus. Maintenance of increased work and peak power was tested during repetitive fatigue-inducing stimulation using a single load of 40% and a stimulation frequency of 20 Hz. Work and peak power of both diaphragm and EDL were augmented by DAP for considerable periods of time, whereas that of soleus muscle was not affected significantly. These results demonstrate that DAP greatly improves both work and peak power of the diaphragm and EDL muscle during isotonic contractions, which combined with previous data on isometric contractions indicates that this agent is suitable for enhancing muscle performance during a range of contractile modalities.

  11. Acute pergolide exposure stiffens engineered valve interstitial cell tissues and reduces contractility in vitro.

    Science.gov (United States)

    Capulli, Andrew K; MacQueen, Luke A; O'Connor, Blakely B; Dauth, Stephanie; Parker, Kevin Kit

    2016-01-01

    Medications based on ergoline-derived dopamine and serotonin agonists are associated with off-target toxicities that include valvular heart disease (VHD). Reports of drug-induced VHD resulted in the withdrawal of appetite suppressants containing fenfluramine and phentermine from the US market in 1997 and pergolide, a Parkinson's disease medication, in 2007. Recent evidence suggests that serotonin receptor activity affected by these medications modulates cardiac valve interstitial cell activation and subsequent valvular remodeling, which can lead to cardiac valve fibrosis and dysfunction similar to that seen in carcinoid heart disease. Failure to identify these risks prior to market and continued use of similar drugs reaffirm the need to improve preclinical evaluation of drug-induced VHD. Here, we present two complimentary assays to measure stiffness and contractile stresses generated by engineered valvular tissues in vitro. As a case study, we measured the effects of acute (24 h) pergolide exposure to engineered porcine aortic valve interstitial cell (AVIC) tissues. Pergolide exposure led to increased tissue stiffness, but it decreased both basal and active contractile tone stresses generated by AVIC tissues. Pergolide exposure also disrupted AVIC tissue organization (i.e., tissue anisotropy), suggesting that the mechanical properties and contractile functionality of these tissues are governed by their ability to maintain their structure. We expect further use of these assays to identify off-target drug effects that alter the phenotypic balance of AVICs, disrupt their ability to maintain mechanical homeostasis, and lead to VHD. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Kaurane and pimarane-type diterpenes from the Viguiera species inhibit vascular smooth muscle contractility.

    Science.gov (United States)

    Ambrosio, Sergio R; Tirapelli, Carlos R; da Costa, Fernando B; de Oliveira, Ana M

    2006-08-01

    The research, development and use of natural products as therapeutic agents, especially those derived from plants, have been increasing in recent years. Despite the fact that plants provide a rich source of novel biologically active compounds, only a small percentage have been phytochemically investigated and studied for their medical potential. Viguiera is a genus that belongs to the family Asteraceae and to the sunflower tribe Heliantheae, which is widespread mostly in Mexico and in other areas of the Andes and upland areas of Brazil. A review on the secondary metabolites pointed out that sesquiterpene lactones and diterpenes, of the kaurane and pimarane-type, are the main compounds produced by these plants. Some reports have shown that kaurane- and pimarane-type diterpenes exert several biological activities such as anti-inflammatory action, antimicrobial and antispasmodic activities. Kaurenoic and pimaradienoic acids, which are the main secondary metabolites isolated by our research group from the roots of Viguiera robusta and V. arenaria, respectively, have been evaluated on vascular smooth muscle contractility. We showed that these diterpenoids are able to inhibit the vascular contractility mainly by blocking extracellular Ca(2+) influx. Additionally, in this review we discuss the structure-activity relationship of the diterpenes regarding their inhibitory activity on vascular contractility.

  13. Impaired contractility and remodeling of the upper gastrointestinal tract in diabetes mellitus type-1.

    Science.gov (United States)

    Frokjaer, Jens Brondum; Andersen, Soren-Due; Ejskjaer, Niels; Funch-Jensen, Peter; Drewes, Asbjorn-Mohr; Gregersen, Hans

    2007-09-28

    To investigate that both the neuronal function of the contractile system and structural apparatus of the gastrointestinal tract are affected in patients with longstanding diabetes and auto mic neuropathy. The evoked esophageal and duodenal contractile activity to standardized bag distension was assessed using a specialized ultrasound-based probe. Twelve type-1 diabetic patients with autonomic neuropathy and severe gastrointestinal symptoms and 12 healthy controls were studied. The geometry and biomechanical parameters (strain, tension/stress, and stiffness) were assessed. The diabetic patients had increased frequency of distension-induced contractions (6.0 +/- 0.6 vs 3.3 +/- 0.5, P 0.14). The impaired contractile activity with an imbalance in the distension-induced contractions likely reflects neuronal abnormalities due to autonomic neuropathy. However, structural changes and remodeling of the gastrointestinal tract are also evident and may add to the neuronal changes. This may contribute to the pathophysiology of diabetic gut dysfunction and impact on future management of diabetic patients with gastrointestinal symptoms.

  14. Acute Pergolide Exposure Stiffens Engineered Valve Interstitial Cell Tissues and Reduces Contractility In Vitro

    Science.gov (United States)

    Capulli, Andrew K.; MacQueen, Luke A.; O’Connor, Blakely B.; Dauth, Stephanie; Parker, Kevin Kit

    2016-01-01

    Medications based on ergoline-derived dopamine and serotonin agonists are associated with off-target toxicities that include valvular heart disease (VHD). Reports of drug-induced VHD resulted in the withdrawal of appetite suppressants containing fenfluramine and phentermine from the U.S. market in 1997 and pergolide, a Parkinson’s disease medication, in 2007. Recent evidence suggests that serotonin receptor activity affected by these medications modulates cardiac valve interstitial cell activation and subsequent valvular remodeling, which can lead to cardiac valve fibrosis and dysfunction similar to that seen in carcinoid heart disease. Failure to identify these risks prior to market, and continued use of similar drugs, reaffirms the need to improve preclinical evaluation of drug-induced VHD. Here, we present two complimentary assays to measure stiffness and contractile stresses generated by engineered valvular tissues in vitro. As a case study, we measured the effects of acute (24 hr) pergolide exposure to engineered porcine aortic valve interstitial cell (AVIC) tissues. Pergolide exposure led to increased tissue stiffness but it decreased both basal and active contractile tone stresses generated by AVIC tissues. Pergolide exposure also disrupted AVIC tissue organization (i.e., tissue anisotropy), suggesting that the mechanical properties and contractile functionality of these tissues are governed by their ability to maintain their structure. We expect further use of these assays to identify off-target drug effects that alter the phenotypic balance of AVICs, disrupt their ability to maintain mechanical homeostasis, and lead to VHD. PMID:27174867

  15. Robust gap repair in the contractile ring ensures timely completion of cytokinesis.

    Science.gov (United States)

    Silva, Ana M; Osório, Daniel S; Pereira, Antonio J; Maiato, Helder; Pinto, Inês Mendes; Rubinstein, Boris; Gassmann, Reto; Telley, Ivo Andreas; Carvalho, Ana Xavier

    2016-12-19

    Cytokinesis in animal cells requires the constriction of an actomyosin contractile ring, whose architecture and mechanism remain poorly understood. We use laser microsurgery to explore the biophysical properties of constricting rings in Caenorhabditis elegans embryos. Laser cutting causes rings to snap open. However, instead of disintegrating, ring topology recovers and constriction proceeds. In response to severing, a finite gap forms and is repaired by recruitment of new material in an actin polymerization-dependent manner. An open ring is able to constrict, and rings repair from successive cuts. After gap repair, an increase in constriction velocity allows cytokinesis to complete at the same time as controls. Our analysis demonstrates that tension in the ring increases while net cortical tension at the site of ingression decreases throughout constriction and suggests that cytokinesis is accomplished by contractile modules that assemble and contract autonomously, enabling local repair of the actomyosin network. Consequently, cytokinesis is a highly robust process impervious to discontinuities in contractile ring structure. © 2016 Silva et al.

  16. Morphometric Parameters, Contractility and Architecture of the Left Ventricle Myocardium in Pigs

    Directory of Open Access Journals (Sweden)

    Mikhail P. Roshchevsky, PhD, ScD

    2012-03-01

    Full Text Available This study aims to reveal the interrelations found within the architecture of the muscular fibers, the morphometric parameters and contractility of the left ventricular myocardium in the Landrace breed of conventional pigs. The left ventricular morphometric parameters were investigated at three levels (basal, middle, apical utilizing echocardiography, myocardial contractility was estimated by the ejection fraction, fractional shortening and fractional thickening. The fiber architecture of the working myocardium was studied following the method of the layer-by-layer splitting of muscular fibers. The fibers ofthe superficial and deep layers of the left ventricle showed an oblique orientation, while the muscular fibers of the middle layer were distinguishable as high-lying and low-lying fibers. During the cardiac cycle, the greatest reduction in the transverse dimension and the greatest thickening of the walls were observed in the middle level when compared with the basal and apical levels, that is related with more thick layer of muscular circumferential fibers in the middle section of the ventricle and large papillary muscles. A low contractile ability of the left ventricle myocardium was revealed in pigs.

  17. Morphology, ultrastructure and contractile properties of muscles responsible for superior tentacle movements of the snail.

    Science.gov (United States)

    Krajcs, Nóra; Márk, L; Elekes, K; Kiss, T

    2012-01-01

    Bending, twitching and quivering are different types of tentacle movements observed during olfactory orientation of the snail. Three recently discovered special muscles, spanning along the length of superior tentacles from the tip to the base, seem to be responsible for the execution of these movements. In this study we have investigated the ultrastructure, contractile properties and protein composition of these muscles. Our ultrastructural studies show that smooth muscle fibers are loosely embedded in a collagen matrix and they are coupled with long sarcolemma protrusions. The muscle fibers apparently lack organized SR and transverse tubular system. Instead subsarcolemmal vesicles and mitochondria have been shown to be possible Ca2+ pools for contraction. It was shown that external Ca2+ is required for contraction elicited by high (40 mM) K+ or 10-4 M ACh. Caffeine (5 mM) induced contraction in Ca2+-free solution suggesting the presence of a substantial intracellular Ca2+ pool. High-resolution electrophoretic analysis of columellar and tentacular muscles did not reveal differences in major contractile proteins, such as actin, myosin and paramyosin. Differences were observed however in several bands representing presumably regulatory enzymes. It is concluded that, the ultrastructural, biochemical and contractile properties of the string muscles support their special physiological function.

  18. Short term doxycycline treatment induces sustained improvement in myocardial infarction border zone contractility.

    Science.gov (United States)

    Spaulding, Kimberly; Takaba, Kiyoaki; Collins, Alexander; Faraji, Farshid; Wang, Guanying; Aguayo, Esteban; Ge, Liang; Saloner, David; Wallace, Arthur W; Baker, Anthony J; Lovett, David H; Ratcliffe, Mark B

    2018-01-01

    Decreased contractility in the non-ischemic border zone surrounding a MI is in part due to degradation of cardiomyocyte sarcomeric components by intracellular matrix metalloproteinase-2 (MMP-2). We recently reported that MMP-2 levels were increased in the border zone after a MI and that treatment with doxycycline for two weeks after MI was associated with normalization of MMP-2 levels and improvement in ex-vivo contractile protein developed force in the myocardial border zone. The purpose of the current study was to determine if there is a sustained effect of short term treatment with doxycycline (Dox) on border zone function in a large animal model of antero-apical myocardial infarction (MI). Antero-apical MI was created in 14 sheep. Seven sheep received doxycycline 0.8 mg/kg/hr IV for two weeks. Cardiac MRI was performed two weeks before, and then two and six weeks after MI. Two sheep died prior to MRI at six weeks from surgical/anesthesia-related causes. The remaining 12 sheep completed the protocol. Doxycycline induced a sustained reduction in intracellular MMP-2 by Western blot (3649±643 MI+Dox vs 9236±114 MI relative intensity; p = 0.0009), an improvement in ex-vivo contractility (65.3±2.0 MI+Dox vs 39.7±0.8 MI mN/mm2; pborder zone six weeks after MI. These findings were associated with a reduction in intracellular MMP-2 activity.

  19. Adaptive responses of mouse skeletal muscle to contractile activity: The effect of age.

    Science.gov (United States)

    Vasilaki, A; McArdle, F; Iwanejko, L M; McArdle, A

    2006-11-01

    This study has characterised the time course of two major transcriptional adaptive responses to exercise (changes in antioxidant defence enzyme activity and heat shock protein (HSP) content) in muscles of adult and old male mice following isometric contractions and has examined the mechanisms involved in the age-related reduction in transcription factor activation. Muscles of B6XSJL mice were subjected to isometric contractions and analysed for antioxidant defence enzyme activities, heat shock protein content and transcription factor DNA binding activity. Data demonstrated a significant increase in superoxide dismutase (SOD) and catalase activity and HSP content of muscles of adult mice following contractile activity which was associated with increased activation of the transcription factors, nuclear factor-kappaB (NF-kappaB), activator protein-1 (AP-1) and heat shock factor (HSF) following contractions. Significant increases in SOD and catalase activity and heat shock cognate (HSC70) content were seen in quiescent muscles of old mice. The increase in antioxidant defence enzyme activity following contractile activity seen in muscles of adult mice was not seen in muscles of old mice and this was associated with a failure to fully activate NF-kappaB and AP-1 following contractions. In contrast, although the production of HSPs was also reduced in muscles of old mice following contractile activity compared with muscles of adult mice following contractions, this was not due to a gross reduction in the DNA binding activity of HSF.

  20. Spontaneous baryogenesis in warm inflation

    OpenAIRE

    Brandenberger, Robert H.; Yamaguchi, Masahide

    2003-01-01

    We discuss spontaneous baryogenesis in the warm inflation scenario. In contrast with standard inflation models, radiation always exists in the warm inflation scenario, and the inflaton must be directly coupled to it. Also, the transition to the post-inflationary radiation dominated phase is smooth and the entropy is not significantly increased at the end of the period of inflation. In addition, after the period of warm inflation ends, the inflaton does not oscillate coherently but slowly roll...

  1. Galectin-3 and fibulin-1 in systolic heart failure - relation to glucose metabolism and left ventricular contractile reserve

    OpenAIRE

    Holmager, Pernille; Egstrup, Michael; Gustafsson, Ida; Schou, Morten; Dahl, Jordi S.; Rasmussen, Lars Melholt; M?ller, Jacob E.; Tuxen, Christian; Faber, Jens; Kistorp, Caroline

    2017-01-01

    Background: Heart failure (HF) patients with diabetes (DM) have an adverse prognosis and reduced functional capacity, which could be associated with cardiac fibrosis, increased chamber stiffness and reduced left ventricular (LV) contractile reserve. Galectin-3 (Gal-3) and fibulin-1 are circulating biomarkers potentially reflecting cardiac fibrosis. We hypothesize that plasma levels of Gal-3 and fibulin-1 are elevated in HF patients with DM and are associated with reduced LV contractile reserv...

  2. Spontaneous Splenic Rupture in Melanoma

    Directory of Open Access Journals (Sweden)

    Hadi Mirfazaelian

    2014-01-01

    Full Text Available Spontaneous rupture of spleen due to malignant melanoma is a rare situation, with only a few case reports in the literature. This study reports a previously healthy, 30-year-old man who came with chief complaint of acute abdominal pain to emergency room. On physical examination, abdominal tenderness and guarding were detected to be coincident with hypotension. Ultrasonography revealed mild splenomegaly with moderate free fluid in abdominopelvic cavity. Considering acute abdominal pain and hemodynamic instability, he underwent splenectomy with splenic rupture as the source of bleeding. Histologic examination showed diffuse infiltration by tumor. Immunohistochemical study (positive for S100, HMB45, and vimentin and negative for CK, CD10, CK20, CK7, CD30, LCA, EMA, and chromogranin confirmed metastatic malignant melanoma. On further questioning, there was a past history of a nasal dark skin lesion which was removed two years ago with no pathologic examination. Spontaneous (nontraumatic rupture of spleen is an uncommon situation and it happens very rarely due to neoplastic metastasis. Metastasis of malignant melanoma is one of the rare causes of the spontaneous rupture of spleen.

  3. Novel method to study pericyte contractility and responses to ischaemia in vitro using electrical impedance.

    Science.gov (United States)

    Neuhaus, Ain A; Couch, Yvonne; Sutherland, Brad A; Buchan, Alastair M

    2017-06-01

    Pericytes are contractile vascular mural cells overlying capillary endothelium, and they have been implicated in a variety of functions including regulation of cerebral blood flow. Recent work has suggested that both in vivo and ex vivo, ischaemia causes pericytes to constrict and die, which has implications for microvascular reperfusion. Assessing pericyte contractility in tissue slices and in vivo is technically challenging, while in vitro techniques remain unreliable. Here, we used isolated cultures of human brain vascular pericytes to examine their contractile potential in vitro using the iCelligence electrical impedance system. Contraction was induced using the vasoactive peptide endothelin-1, and relaxation was demonstrated using adenosine and sodium nitroprusside. Endothelin-1 treatment also resulted in increased proliferation, which we were able to monitor in the same cell population from which we recorded contractile responses. Finally, the observation of pericyte contraction in stroke was reproduced using chemical ischaemia, which caused a profound and irreversible contraction clearly preceding cell death. These data demonstrate that isolated pericytes retain a contractile phenotype in vitro, and that it is possible to quantify this contraction using real-time electrical impedance recordings, providing a significant new platform for assessing the effects of vasoactive and vasculoprotective compounds on pericyte contractility.

  4. Heightened Pelvic Floor Muscle Tone and Altered Contractility in Women With Provoked Vestibulodynia.

    Science.gov (United States)

    Morin, Mélanie; Binik, Yitzchak M; Bourbonnais, Daniel; Khalifé, Samir; Ouellet, Stéphane; Bergeron, Sophie

    2017-04-01

    Pelvic floor muscle (PFM) dysfunctions are reported to be involved in provoked vestibulodynia (PVD). Although heightened PFM tone has been suggested, the relative contribution of active and passive components of tone remains misunderstood. Likewise, alterations in PFM contractility have been scarcely studied. To compare PFM tone, including the relative contribution of its active and passive components, and muscular contractility in women with PVD and asymptomatic controls. Fifty-six asymptomatic women and 56 women with PVD participated in the study. The PVD diagnosis was confirmed by a gynecologist based on a standardized examination. PFM function was evaluated using a dynamometric speculum combined with surface electromyography (EMG). PFM general tone was evaluated in static conditions at different vaginal apertures and during repeated dynamic cyclic stretching. The active contribution of tone was characterized using the ratio between EMG in a static position and during stretching and the proportion of women presenting PFM activation during stretching. Contribution of the passive component was evaluated using resting forces, stiffness, and hysteresis in women sustaining a negligible EMG signal during stretching. PFM contractility, such as strength, speed of contraction, coordination, and endurance, also was assessed during voluntary isometric efforts. Greater PFM resting forces and stiffness were found in women with PVD compared with controls, indicating an increased general tone. An increased active component also was found in women with PVD because they presented a superior EMG ratio, and a larger proportion of them presented PFM activation during stretching. Higher passive properties also were found in women with PVD. Women with PVD also showed decreased strength, speed of contraction, coordination, and endurance compared with controls. Findings provide further evidence of the contribution of PFM alterations in the etiology of PVD. These alterations should be

  5. Myocardial contractility in the echo lab: molecular, cellular and pathophysiological basis

    Directory of Open Access Journals (Sweden)

    Bombardini Tonino

    2005-09-01

    Full Text Available Abstract In the standard accepted concept, contractility is the intrinsic ability of heart muscle to generate force and to shorten, independently of changes in the preload or afterload with fixed heart rates. At molecular level the crux of the contractile process lies in the changing concentrations of Ca2+ ions in the myocardial cytosol. Ca2+ ions enter through the calcium channel that opens in response to the wave of depolarization that travels along the sarcolemma. These Ca2+ ions "trigger" the release of more calcium from the sarcoplasmic reticulum (SR and thereby initiate a contraction-relaxation cycle. In the past, several attempts were made to transfer the pure physiological concept of contractility, expressed in the isolated myocardial fiber by the maximal velocity of contraction of unloaded muscle fiber (Vmax, to the in vivo beating heart. Suga and Sagawa achieved this aim by measuring pressure/volume loops in the intact heart: during a positive inotropic intervention, the pressure volume loop reflects a smaller end-systolic volume and a higher end-systolic pressure, so that the slope of the pressure volume relationship moves upward and to the left. The pressure volume relationship is the most reliable index for assessing myocardial contractility in the intact circulation and is almost insensitive to changes in preload and after load. This is widely used in animal studies and occasionally clinically. The limit of the pressure volume relationship is that it fails to take into account the frequency-dependent regulation of contractility: the frequency-dependent control of transmembrane Ca2+ entry via voltage-gated Ca2+ channels provides cardiac cells with a highly sophisticated short-term system for the regulation of intracellular Ca2+ homeostasis. An increased stimulation rate increases the force of contraction: the explanation is repetitive Ca2+ entry with each depolarization and, hence, an accumulation of cytosolic calcium. As the heart

  6. Spontaneous oscillations in microfluidic networks

    Science.gov (United States)

    Case, Daniel; Angilella, Jean-Regis; Motter, Adilson

    2017-11-01

    Precisely controlling flows within microfluidic systems is often difficult which typically results in systems being heavily reliant on numerous external pumps and computers. Here, I present a simple microfluidic network that exhibits flow rate switching, bistablity, and spontaneous oscillations controlled by a single pressure. That is, by solely changing the driving pressure, it is possible to switch between an oscillating and steady flow state. Such functionality does not rely on external hardware and may even serve as an on-chip memory or timing mechanism. I use an analytic model and rigorous fluid dynamics simulations to show these results.

  7. General features of spontaneous baryogenesis

    Science.gov (United States)

    Arbuzova, Elena

    2017-04-01

    The classical version of spontaneous baryogenesis is studied in details. It is shown that the relation between the time derivative of the (pseudo)goldstone field and the baryonic chemical potential essentially depends upon the representation chosen for the fermionic fields with non-zero baryonic number (quarks). The kinetic equation, used for the calculations of the cosmological baryon asymmetry, is generalized to the case of non-stationary background. The effects of the finite interval of the integration over time are also included into consideration.

  8. Spontaneous osteonecrosis of the knee

    Energy Technology Data Exchange (ETDEWEB)

    Kattapuram, Taj M. [Department of Radiology, Massachusetts General Hospital (United States); Kattapuram, Susan V. [Department of Radiology, Massachusetts General Hospital (United States)], E-mail: skattapuram@partners.org

    2008-07-15

    Spontaneous osteonecrosis of the knee presents with acute onset of severe, pain in elderly patients, usually female and usually without a history of trauma. Originally described as idiopathic osteonecrosis, the exact etiology is still debated. Evidence suggests that an acute fracture occurs as a result of chronic stress or minor trauma to a weakened subchondral bone plate. The imaging characteristics on MR reflect the age of the lesion and the symptoms. More appropriate terminology may be ' subchondral insufficiency fracture of the knee' or 'focal subchondral osteonecrosis'.

  9. Radiological evaluation of spontaneous pneumoperitoneum

    International Nuclear Information System (INIS)

    Kim, H. S.; Kim, J. D.; Rhee, H. S.

    1982-01-01

    112 cases of spontaneous penumoperitoneum, the causes of which were confirmed by clinical and surgical procedure at Presbyterian Medical Center from January, 1977 to July, 1981 were reviewed radiologically. The results were as follows: 1. Perforation of duodenal ulcer (46/112: 41.1%), stomach ulcer (22/112: 19.6%), and stomach cancer (11/112: 9.8%) were the three most common causes of spontaneous penumoperitoneum. These were 70.5% of all causes. 2. The most common site of free gas was both subdiaphragmatic areas (46: 41.1%). Others were Rt. subdiaphragmatic only (31: 27.7%), both subdiaphragmatic with subhepatic (16: 14.3%), Rt. subdiaphragmatic with subhepatic (7: 6.2%), Rt. subdiaphragmatic only (5: 4.4%), diffuse in abdomen (4: 3.6%), and subhepatic only (3: 2.7%). So 92.0% (103/112) were located in RUQ. 3. The radiological shape of free gas was classified: crescent (52: 46.4%) of small amount; half-moon (21: 18.8%) of moderate amount; large or diffuse (39: 34.8%) of large amount.4. The age between 31 and 60 occupied 69.1% (77/112), and male was predominant (5.2 times). 5. The patient's position showing free air most frequently was erect

  10. A Case of Multiple Spontaneous Keloid Scars

    Directory of Open Access Journals (Sweden)

    Abdulhadi Jfri

    2015-07-01

    Full Text Available Keloid scars result from an abnormal healing response to cutaneous injury or inflammation that extends beyond the borders of the original wound. Spontaneous keloid scars forming in the absence of any previous trauma or surgical procedure are rare. Certain syndromes have been associated with this phenomenon, and few reports have discussed the evidence of single spontaneous keloid scar, which raises the question whether they are really spontaneous. Here, we present a 27-year-old mentally retarded single female with orbital hypertelorism, broad nasal bridge, repaired cleft lip and high-arched palate who presented with progressive multiple spontaneous keloid scars in different parts of her body which were confirmed histologically by the presence of typical keloidal collagen. This report supports the fact that keloid scars can appear spontaneously and are possibly linked to a genetic factor. Furthermore, it describes a new presentation of spontaneous keloid scars in the form of multiple large lesions in different sites of the body.

  11. Spontaneity of communication in individuals with autism.

    Science.gov (United States)

    Chiang, Hsu-Min; Carter, Mark

    2008-04-01

    This article provides an examination of issues related to spontaneity of communication in children with autism. Deficits relating to spontaneity or initiation are frequently reported in individuals with autism, particularly in relation to communication and social behavior. Nevertheless, spontaneity is not necessarily clearly conceptualized or measured. Several approaches to conceptualization of communicative spontaneity are examined with a particular focus on the continuum model and how it might be practically applied. A range of possible explanations for deficits in spontaneity of communication in children with autism is subsequently explored, including external factors (highly structured teaching programs, failure to systematically instruct for spontaneity) and intrinsic characteristics (intellectual disability, stimulus overselectivity, weak central coherence). Possible implications for future research are presented.

  12. GRK2 – A Link Between Myocardial Contractile Function and Cardiac Metabolism

    Science.gov (United States)

    Woodall, Meryl C.; Ciccarelli, Michele; Woodall, Benjamin P.; Koch, Walter J.

    2014-01-01

    Heart failure (HF) causes a tremendous burden on the worldwide healthcare system, affecting more than 23 million people. There are many cardiovascular disorders that contribute to the development of HF and multiple risk factors that accelerate its occurrence, but regardless of its underlying cause, HF is characterized by a marked decrease in myocardial contractility and loss of pump function. One biomarker molecule consistently shown to be upregulated in human HF and several animal models is G protein-coupled receptor (GPCR) kinase 2 (GRK2), a kinase originally discovered to be involved in GPCR desensitization, especially β-adrenergic receptors (βARs). Indeed, higher levels of GRK2 can impair βAR-mediated inotropic reserve and its inhibition or molecular reduction has shown to improve pump function in several animal models including a pre-clinical pig model of HF. Recently, non-classical roles for GRK2 in cardiovascular disease have been described, including negative regulation of insulin signaling, a role in myocyte cell survival and apoptotic signaling, and it has been shown to be localized in/on mitochondria. These new roles of GRK2 suggest that GRK2 may be a nodal link in the myocyte, influencing both cardiac contractile function and cell metabolism and survival and contributing to HF independent of its canonical role on GPCR desensitization. In this review, classical and non-classical roles for GRK2 will be discussed, focusing on recently discovered roles for GRK2 in cardiomyocyte metabolism and the effects that these roles may have on myocardial contractile function and HF development. PMID:24812353

  13. The role of apical contractility in determining cell morphology in multilayered epithelial sheets and tubes

    Science.gov (United States)

    Zhen Tan, Rui; Lai, Tanny; Chiam, K.-H.

    2017-08-01

    A multilayered epithelium is made up of individual cells that are stratified in an orderly fashion, layer by layer. In such tissues, individual cells can adopt a wide range of shapes ranging from columnar to squamous. From histological images, we observe that, in flat epithelia such as the skin, the cells in the top layer are squamous while those in the middle and bottom layers are columnar, whereas in tubular epithelia, the cells in all layers are columnar. We develop a computational model to understand how individual cell shape is governed by the mechanical forces within multilayered flat and curved epithelia. We derive the energy function for an epithelial sheet of cells considering intercellular adhesive and intracellular contractile forces. We determine computationally the cell morphologies that minimize the energy function for a wide range of cellular parameters. Depending on the dominant adhesive and contractile forces, we find four dominant cell morphologies for the multilayered-layered flat sheet and three dominant cell morphologies for the two-layered curved sheet. We study the transitions between the dominant cell morphologies for the two-layered flat sheet and find both continuous and discontinuous transitions and also the presence of multistable states. Matching our computational results with histological images, we conclude that apical contractile forces from the actomyosin belt in the epithelial cells is the dominant force determining cell shape in multilayered epithelia. Our computational model can guide tissue engineers in designing artificial multilayered epithelia, in terms of figuring out the cellular parameters needed to achieve realistic epithelial morphologies.

  14. Changes in muscle fiber contractility and extracellular matrix production during skeletal muscle hypertrophy.

    Science.gov (United States)

    Mendias, Christopher L; Schwartz, Andrew J; Grekin, Jeremy A; Gumucio, Jonathan P; Sugg, Kristoffer B

    2017-03-01

    Skeletal muscle can adapt to increased mechanical loads by undergoing hypertrophy. Transient reductions in whole muscle force production have been reported during the onset of hypertrophy, but contractile changes in individual muscle fibers have not been previously studied. Additionally, the extracellular matrix (ECM) stores and transmits forces from muscle fibers to tendons and bones, and determining how the ECM changes during hypertrophy is important in understanding the adaptation of muscle tissue to mechanical loading. Using the synergist ablation model, we sought to measure changes in muscle fiber contractility, collagen content, and cross-linking, and in the expression of several genes and activation of signaling proteins that regulate critical components of myogenesis and ECM synthesis and remodeling during muscle hypertrophy. Tissues were harvested 3, 7, and 28 days after induction of hypertrophy, and nonoverloaded rats served as controls. Muscle fiber specific force (sF o ), which is the maximum isometric force normalized to cross-sectional area, was reduced 3 and 7 days after the onset of mechanical overload, but returned to control levels by 28 days. Collagen abundance displayed a similar pattern of change. Nearly a quarter of the transcriptome changed over the course of overload, as well as the activation of signaling pathways related to hypertrophy and atrophy. Overall, this study provides insight into fundamental mechanisms of muscle and ECM growth, and indicates that although muscle fibers appear to have completed remodeling and regeneration 1 mo after synergist ablation, the ECM continues to be actively remodeling at this time point. NEW & NOTEWORTHY This study utilized a rat synergist ablation model to integrate changes in single muscle fiber contractility, extracellular matrix composition, activation of important signaling pathways in muscle adaption, and corresponding changes in the muscle transcriptome to provide novel insight into the basic

  15. Update on corpus cavernosum smooth muscle contractile pathways in erectile function: a role for testosterone?

    Science.gov (United States)

    Zhang, Xin-Hua; Melman, Arnold; Disanto, Michael E

    2011-07-01

    Normal erectile function (EF) involves a coordinated relaxation of the arteries that supply the penis and the corpus cavernosum smooth muscle (CCSM), resulting in expansion of the sinusoids and increased intracavernous pressure. But the CCSM spends the majority of its time in the contracted state which is mediated by norepinephrine released from nerve endings and other vasoconstrictors like endothelins released from the endothelium. These agents cause smooth muscle myosin (SMM) phosphorylation by elevating intracellular calcium. When calcium returns to basal levels, the calcium sensitivity increases and prevents myosin dephosphorylation, which involves the RhoA/Rho-kinase (ROK) mechanism, thus maintaining force. Although mounting evidences demonstrate that androgens have a major influence on EF that is not just centrally mediated, this notion remains quite controversial. To summarize the current knowledge on CCSM contractile pathways, the role they play in modulating EF, and the influence of androgens. The article reviews the literature and contains some previously unpublished data on CCSM contraction signaling including the role that androgens are known to play in modulating these pathways. Data from peer-reviewed publications and previously unpublished observations. In addition to downregulation of many pro-erectile molecular mechanisms, decreased testosterone (T) levels upregulate CCSM contractility, including hyperresponsiveness to α-adrenergic agonists, increased SMM phosphorylation, alteration of SMM isoform composition, activation of RhoA/ROK signaling and modulation of sphingosine-1-phosphate regulation of CCSM tone. Decreased T levels upregulate CCSM contractile signaling. Meanwhile, it downregulates CCSM relaxation pathways synergizing to produce erectile dysfunction (ED). Although some urologists and researchers are still skeptical of the influence of androgens on penile erection, understanding these molecular control mechanisms as well as the influence

  16. The effect of exercise hypertrophy and disuse atrophy on muscle contractile properties: a mechanomyographic analysis.

    Science.gov (United States)

    Than, Christian; Tosovic, Danijel; Seidl, Laura; Mark Brown, J

    2016-12-01

    To determine whether mechanomyographic (MMG) determined contractile properties of the biceps brachii change during exercise-induced hypertrophy and subsequent disuse atrophy. Healthy subjects (mean ± SD, 23.7 ± 2.6 years, BMI 21.8 ± 2.4, n = 19) performed unilateral biceps curls (9 sets × 12 repetitions, 5 sessions per week) for 8 weeks (hypertrophic phase) before ceasing exercise (atrophic phase) for the following 8 weeks (non-dominant limb; treatment, dominant limb; control). MMG measures of muscle contractile properties (contraction time; T c , maximum displacement; D max , contraction velocity; V c ), electromyographic (EMG) measures of muscle fatigue (median power frequency; MPF), strength measures (maximum voluntary contraction; MVC) and measures of muscle thickness (ultrasound) were obtained. Two-way repeated measures ANOVA showed significant differences (P muscle thickness was greater than control, reflecting gross hypertrophy. MMG variables Dmax (weeks 2, 7) and Vc (weeks 7, 8) declined. During the atrophic phase, MVC (weeks 9-12) and muscle thickness (weeks 9, 10) initially remained high before declining to control levels, reflecting gross atrophy. MMG variables D max (weeks 9, 14) and V c (weeks 9, 14, 15) also declined during the atrophic phase. No change in T c was found throughout the hypertrophic or atrophic phases. MMG detects changes in contractile properties during stages of exercise-induced hypertrophy and disuse atrophy suggesting its applicability as a clinical tool in musculoskeletal rehabilitation.

  17. Contractility-afterload mismatch in patients with protein-losing enteropathy after the Fontan operation.

    Science.gov (United States)

    Ozawa, Hideto; Ueno, Takayoshi; Iwai, Shigemitsu; Kawata, Hiroaki; Nishigaki, Kyouichi; Kishimoto, Hidefumi; Sawa, Yoshiki

    2014-10-01

    This study aimed to clarify the relationship between onset of protein-losing enteropathy (PLE) and Fontan circulation, with special reference to the development of contractility-afterload mismatch. The PLE group comprised 9 patients who experienced PLE after undergoing the Fontan operation, and the control group consisted of 32 patients had did not experienced PLE more than 10 years after the Fontan operation. The study compared the pre- and postoperative values of arterial elastance (Ea), end-systolic elastance (Ees), and contractility-afterload mismatch (Ea/Ees). Furthermore, the variations in the values were examined during the preoperative, postoperative, and midterm postoperative periods in seven PLE patients who underwent cardiac catheterization at the onset of PLE and during the pre- and postintervention periods in three PLE patients who underwent surgical intervention to improve the Fontan circulation after the onset of PLE. Comparison of the values obtained before and after Fontan operations showed that the Ea values increased significantly in the PLE group. However, the pre- and postoperative Ees values did not differ in the two groups. During the postoperative period, Ea/Ees increased significantly, and the Ea and Ea/Ees values increased continuously until the onset of PLE in the PLE group. In the patients who underwent surgical intervention to improve the Fontan circulation after the onset of PLE, the Ea/Ees decreased significantly, and the serum albumin levels improved after the intervention. Contractility-afterload mismatch, mainly caused by the increase in the afterload of the systemic ventricle, may have an important role in the development of PLE after the Fontan operation.

  18. Alteration of contractile and regulatory proteins in estrogen-induced hypertrophy of female rabbit bladder.

    Science.gov (United States)

    Lin, Alpha Dian-Yu; Levin, Robert M; Kogan, Barry A; Whitbeck, Catherine; Leggett, Robert E; Kearns, Christine; Mannikarottu, Anita

    2006-11-01

    Estrogen is essential to mediate physiologic functions in female bladders. Deficiency of estrogen has been speculated to be an etiologic factor for bladder dysfunction in postmenopausal women. Our previous studies have demonstrated that estrogen supplementation in female rabbits induces a "functional hypertrophy" of the urinary bladder smooth muscle. The present study investigated the alterations in the contractile and regulatory proteins in this model. Twenty New Zealand white female rabbits were separated into five groups of 4 rabbits each. Group 1 served as the control, groups 2 to 6 underwent ovariectomy (Ovx), and group 2 served as the Ovx without estradiol treatment group. Two weeks after Ovx, groups 3 to 5 were given 17-beta estradiol (1 mg/kg/day) by subcutaneous implant for 1, 3, and 7 days, respectively. The expression of the contractile and regulatory proteins, such as myosin light chain kinase, rho-kinase, and caldesmon, was analyzed by Western blotting. The expression of myosin light chain kinase was enhanced by estradiol supplementation. The expression of rho-kinase-alpha was increased significantly (20-fold) after Ovx, which was downregulated after estrogen supplementation. No significant change was seen in rho-kinase-beta after Ovx or estradiol supplementation. The expression of caldesmon isoforms was enhanced by 1-day estradiol supplementation but decreased to lower levels than those of the control group by 3 and 7 days of estrogen treatment. The results of the present study have provided more understanding about the role of the contractile and regulatory proteins in detrusor muscle, in both dysfunctional atrophy induced by Ovx and functional hypertrophy induced by estrogen supplementation.

  19. Dobutamine enhances both contractile function and energy reserves in hypoperfused canine right ventricle.

    Science.gov (United States)

    Yi, K D; Downey, H F; Bian, X; Fu, M; Mallet, R T

    2000-12-01

    Although the beta(1)-adrenergic agent dobutamine is used clinically to provide inotropic support to the failing myocardium, it could jeopardize the myocardium by depleting energy reserves. This investigation delineated the contractile and energetic effects of low versus high dobutamine doses in the hypoperfused right ventricular (RV) myocardium. The right coronary artery (RCA) of anesthetized dogs was cannulated for controlled perfusion with arterial blood, and regional RV contractile function was measured. RCA perfusion pressure was lowered from 100 mmHg baseline to 40 mmHg, and flow fell by 54%. At 15-min hypoperfusion, dobutamine was infused into the RCA at either 0.01 (low-dose dobutamine) or 0.06 microgram. kg(-1). min(-1) (high-dose dobutamine) for 15 min. Regional power (systolic segment shortening x isometric developed force x heart rate) stabilized at 63% of baseline during hypoperfusion. Low-dose dobutamine restored power to baseline but did not increase RV myocardial O(2) consumption (MVO(2)) and thus increased myocardial O(2) utilization efficiency (O(2)UE:power/MVO(2)). At 5 min, high-dose dobutamine enhancement of power was similar to that of low-dose dobutamine, but by 15 min, power and O(2)UE fell to untreated levels. Remarkably, low-dose dobutamine tripled cytosolic phosphorylation potential; in contrast, high-dose dobutamine lowered phosphorylation potential to 45% of the untreated value. Analyses of glucose uptake and glycolytic intermediates revealed sustained enhancement of glycolysis by low-dose dobutamine, but glycolysis became limited at glyceraldehyde 3-phosphate dehydrogenase during high-dose dobutamine treatment. In summary, low-dose dobutamine improved mechanical performance and efficiency of the hypoperfused RV myocardium while increasing myocardial energy reserves, but high-dose dobutamine failed to sustain improved function and depleted energy reserves. Dobutamine is capable of improving both contractile function and cellular

  20. Contractile properties of muscle fibers from the deep and superficial digital flexors of horses.

    Science.gov (United States)

    Butcher, M T; Chase, P B; Hermanson, J W; Clark, A N; Brunet, N M; Bertram, J E A

    2010-10-01

    Equine digital flexor muscles have independent tendons but a nearly identical mechanical relationship to the main joint they act upon. Yet these muscles have remarkable diversity in architecture, ranging from long, unipennate fibers ("short" compartment of DDF) to very short, multipennate fibers (SDF). To investigate the functional relevance of the form of the digital flexor muscles, fiber contractile properties were analyzed in the context of architecture differences and in vivo function during locomotion. Myosin heavy chain (MHC) isoform fiber type was studied, and in vitro motility assays were used to measure actin filament sliding velocity (V(f)). Skinned fiber contractile properties [isometric tension (P(0)/CSA), velocity of unloaded shortening (V(US)), and force-Ca(2+) relationships] at both 10 and 30°C were characterized. Contractile properties were correlated with MHC isoform and their respective V(f). The DDF contained a higher percentage of MHC-2A fibers with myosin (heavy meromyosin) and V(f) that was twofold faster than SDF. At 30°C, P(0)/CSA was higher for DDF (103.5 ± 8.75 mN/mm(2)) than SDF fibers (81.8 ± 7.71 mN/mm(2)). Similarly, V(US) (pCa 5, 30°C) was faster for DDF (2.43 ± 0.53 FL/s) than SDF fibers (1.20 ± 0.22 FL/s). Active isometric tension increased with increasing Ca(2+) concentration, with maximal Ca(2+) activation at pCa 5 at each temperature in fibers from each muscle. In general, the collective properties of DDF and SDF were consistent with fiber MHC isoform composition, muscle architecture, and the respective functional roles of the two muscles in locomotion.

  1. Myocardial mitochondrial and contractile function are preserved in mice lacking adiponectin.

    Directory of Open Access Journals (Sweden)

    Martin Braun

    Full Text Available Adiponectin deficiency leads to increased myocardial infarct size following ischemia reperfusion and to exaggerated cardiac hypertrophy following pressure overload, entities that are causally linked to mitochondrial dysfunction. In skeletal muscle, lack of adiponectin results in impaired mitochondrial function. Thus, it was our objective to investigate whether adiponectin deficiency impairs mitochondrial energetics in the heart. At 8 weeks of age, heart weight-to-body weight ratios were not different between adiponectin knockout (ADQ-/- mice and wildtypes (WT. In isolated working hearts, cardiac output, aortic developed pressure and cardiac power were preserved in ADQ-/- mice. Rates of fatty acid oxidation, glucose oxidation and glycolysis were unchanged between groups. While myocardial oxygen consumption was slightly reduced (-24% in ADQ-/- mice in isolated working hearts, rates of maximal ADP-stimulated mitochondrial oxygen consumption and ATP synthesis in saponin-permeabilized cardiac fibers were preserved in ADQ-/- mice with glutamate, pyruvate or palmitoyl-carnitine as a substrate. In addition, enzymatic activity of respiratory complexes I and II was unchanged between groups. Phosphorylation of AMP-activated protein kinase and SIRT1 activity were not decreased, expression and acetylation of PGC-1α were unchanged, and mitochondrial content of OXPHOS subunits was not decreased in ADQ-/- mice. Finally, increasing energy demands due to prolonged subcutaneous infusion of isoproterenol did not differentially affect cardiac contractility or mitochondrial function in ADQ-/- mice compared to WT. Thus, mitochondrial and contractile function are preserved in hearts of mice lacking adiponectin, suggesting that adiponectin may be expendable in the regulation of mitochondrial energetics and contractile function in the heart under non-pathological conditions.

  2. Spontaneous cryptococcal peritonitis in cirrhotic patients.

    Directory of Open Access Journals (Sweden)

    Sungkanuparph S

    2002-07-01

    Full Text Available Spontaneous bacterial peritonitis is a common complication in patients with cirrhosis and ascites. However, spontaneous peritonitis caused by Cryptococcus neoformans is uncommon. Delayed diagnosis of cryptococcal peritonitis often results in death. We describe three cases of spontaneous cryptococcal peritonitis in patients with decompensated cirrhosis. One case had associated symptomatic human immunodeficiency virus infection. Clinical awareness of this entity may lead to the early diagnosis and proper treatment.

  3. Spontaneous Intracranial Hypotension without Orthostatic Headache

    Directory of Open Access Journals (Sweden)

    Tülay Kansu

    2009-03-01

    Full Text Available We report 2 cases of spontaneous intracranial hypotension that presented with unilateral abducens nerve palsy, without orthostatic headache. While sixth nerve palsies improved without any intervention, subdural hematoma was detected with magnetic resonance imaging. We conclude that headache may be absent in spontaneous intracranial hypotension and spontaneous improvement of sixth nerve palsy can occur, even after the development of a subdural hematoma

  4. Spontaneous renal hematoma - a case report

    International Nuclear Information System (INIS)

    Obrzut, M.; Obrzut, M.; Homa, J.; Obrzut, B.

    2006-01-01

    Spontaneous pararenal hematoma is a rare pathology most frequently coexisting with renal tumours, vascular anomalies and inflammatory processes. In some cases one cannot establish its etiology. The paper describes a case of a 58-year-old man with a spontaneous pararenal hematoma and presents a diagnostic algorithm. Ultrasonography and CT play an important role in diagnostics of spontaneous pararenal haemorrhages. These methods enable a precise evaluation of size and location of hematoma and its evolution. (author)

  5. Interaction Between Troponin and Myosin Enhances Contractile Activity of Myosin in Cardiac Muscle

    OpenAIRE

    Schoffstall, Brenda; LaBarbera, Vincent A.; Brunet, Nicolas M.; Gavino, Belinda J.; Herring, Lauren; Heshmati, Sara; Kraft, Brittany H.; Inchausti, Vanessa; Meyer, Nancy L.; Moonoo, Danamarie; Takeda, Aya K.; Chase, Prescott Bryant

    2011-01-01

    Ca2+ signaling in striated muscle cells is critically dependent upon thin filament proteins tropomyosin (Tm) and troponin (Tn) to regulate mechanical output. Using in vitro measurements of contractility, we demonstrate that even in the absence of actin and Tm, human cardiac Tn (cTn) enhances heavy meromyosin MgATPase activity by up to 2.5-fold in solution. In addition, cTn without Tm significantly increases, or superactivates sliding speed of filamentous actin (F-actin) in skeletal motility a...

  6. Prolonged ischemic heart disease and coronary artery bypass - relation to contractile reserve

    DEFF Research Database (Denmark)

    Kofoed, Klaus F; Bangsgaard, Regitze; Carstensen, Steen

    2002-01-01

    OBJECTIVE: A major effect of coronary artery bypass grafting (CABG) in patients with ischemic heart disease and impaired left ventricular (LV) contractile function is believed to be an improvement in LV function due to recovery of dysfunctional, but viable myocardium. However, recent studies have...... indicated a time limit for such a recovery. We therefore investigated the extent of viable myocardium in patients with impaired LV function due to ischemic heart disease after a prolonged strategy of medical treatment and its relation to changes in clinical variables after CABG. METHODS: Forty......-five consecutive patients with a mean duration of ischemic heart symptoms of 9 years and LV ejection fraction (EF) stress...

  7. Post-exercise contractility, diastolic function, and pressure: Operator-independent sensor-based intelligent monitoring for heart failure telemedicine

    Directory of Open Access Journals (Sweden)

    Giannoni Massimo

    2009-05-01

    Full Text Available Abstract Background New sensors for intelligent remote monitoring of the heart should be developed. Recently, a cutaneous force-frequency relation recording system has been validated based on heart sound amplitude and timing variations at increasing heart rates. Aim To assess sensor-based post-exercise contractility, diastolic function and pressure in normal and diseased hearts as a model of a wireless telemedicine system. Methods We enrolled 150 patients and 22 controls referred for exercise-stress echocardiography, age 55 ± 18 years. The sensor was attached in the precordial region by an ECG electrode. Stress and recovery contractility were derived by first heart sound amplitude vibration changes; diastolic times were acquired continuously. Systemic pressure changes were quantitatively documented by second heart sound recording. Results Interpretable sensor recordings were obtained in all patients (feasibility = 100%. Post-exercise contractility overshoot (defined as increase > 10% of recovery contractility vs exercise value was more frequent in patients than controls (27% vs 8%, p 1 in 20 patients and in none of the controls (p 1 in only 3 patients (p Conclusion Post-exercise contractility, diastolic time and pressure changes can be continuously measured by a cutaneous sensor. Heart disease affects not only exercise systolic performance, but also post-exercise recovery, diastolic time intervals and blood pressure changes – in our study, all of these were monitored by a non-invasive wearable sensor.

  8. Blebbistain, a myosin II inhibitor, as a novel strategy to regulate detrusor contractility in a rat model of partial bladder outlet obstruction.

    Directory of Open Access Journals (Sweden)

    Xinhua Zhang

    Full Text Available Partial bladder outlet obstruction (PBOO, a common urologic pathology mostly caused by benign prostatic hyperplasia, can coexist in 40-45% of patients with overactive bladder (OAB and is associated with detrusor overactivity (DO. PBOO that induces DO results in alteration in bladder myosin II type and isoform composition. Blebbistatin (BLEB is a myosin II inhibitor we recently demonstrated potently relaxed normal detrusor smooth muscle (SM and reports suggest varied BLEB efficacy for different SM myosin (SMM isoforms and/or SMM vs nonmuscle myosin (NMM. We hypothesize BLEB inhibition of myosin II as a novel contraction protein targeted strategy to regulate DO. Using a surgically-induced male rat PBOO model, organ bath contractility, competitive and Real-Time-RT-PCR were performed. It was found that obstructed-bladder weight significantly increased 2.74-fold while in vitro contractility of detrusor to various stimuli was impaired ∼50% along with decreased shortening velocity. Obstruction also altered detrusor spontaneous activities with significantly increased amplitude but depressed frequency. PBOO switched bladder from a phasic-type to a more tonic-type SM. Expression of 5' myosin heavy chain (MHC alternatively spliced isoform SM-A (associated with tonic-type SM increased 3-fold while 3' MHC SM1 and essential light chain isoform MLC(17b also exhibited increased relative expression. Total SMMHC expression was decreased by 25% while the expression of NMM IIB (SMemb was greatly increased by 4.5-fold. BLEB was found to completely relax detrusor strips from both sham-operated and PBOO rats pre-contracted with KCl, carbachol or electrical field stimulation although sensitivity was slightly decreased (20% only at lower doses for PBOO. Thus we provide the first thorough characterization of the response of rat bladder myosin to PBOO and demonstrate complete BLEB-induced PBOO bladder SM relaxation. Furthermore, the present study provides valuable

  9. Biomarkers of spontaneous preterm birth

    DEFF Research Database (Denmark)

    Polettini, Jossimara; Cobo, Teresa; Kacerovsky, Marian

    2017-01-01

    predictors of pregnancy outcome. This systematic review was conducted to synthesize the knowledge on PTB biomarkers identified using multiplex analysis. Three electronic databases (PubMed, EMBASE and Web of Science) were searched for studies in any language reporting the use of multiplex assays for maternal......Despite decades of research on risk indicators of spontaneous preterm birth (PTB), reliable biomarkers are still not available to screen or diagnose high-risk pregnancies. Several biomarkers in maternal and fetal compartments have been mechanistically linked to PTB, but none of them are reliable......) followed by MIP-1β, GM-CSF, Eotaxin, and TNF-RI (two studies) were reported more than once in maternal serum. However, results could not be combined due to heterogeneity in type of sample, study population, assay, and analysis methods. By this systematic review, we conclude that multiplex assays...

  10. Spontaneous Strategies in Innovation Networks

    DEFF Research Database (Denmark)

    Plesner, Ursula; Husted, Emil Krastrup

    and a site ontology, we show how physical sites and objects become constitutive of the inside of virtual worlds through innovation processes. This argument is in line with ANT’s perspective on strategy, where sites and objects are considered a strategically relevant resource in the innovation process...... of materiality in relation to the organization and structuring of virtual worlds. We examine various innovation processes in five Danish entrepreneurial companies where actors continuously struggle to stabilize virtual worlds as platforms for professional communication. With inspiration from actor-network theory....... Empirically, the analysis is founded on descriptive accounts from the five entrepreneurs. By highlighting the spontaneous strategies described by actors, we show how sites and objects are actively used as an element in their strategy, and also how the sites and objects end up facilitating new ways of thinking...

  11. Recurrent spontaneous attacks of dizziness.

    Science.gov (United States)

    Lempert, Thomas

    2012-10-01

    This article describes the common causes of recurrent vertigo and dizziness that can be diagnosed largely on the basis of history. Ninety percent of spontaneous recurrent vertigo and dizziness can be explained by six disorders: (1) Ménière disease is characterized by vertigo attacks, lasting 20 minutes to several hours, with concomitant hearing loss, tinnitus, and aural fullness. Aural symptoms become permanent during the course of the disease. (2) Attacks of vestibular migraine may last anywhere from minutes to days. Most patients have a previous history of migraine headaches, and many experience migraine symptoms during the attack. (3) Vertebrobasilar TIAs affect older adults with vascular risk factors. Most attacks last less than 1 hour and are accompanied by other symptoms from the posterior circulation territory. (4) Vestibular paroxysmia is caused by vascular compression of the eighth cranial nerve. It manifests itself with brief attacks of vertigo that recur many times per day, sometimes with concomitant cochlear symptoms. (5) Orthostatic hypotension causes brief episodes of dizziness lasting seconds to a few minutes after standing up and is relieved by sitting or lying down. In older adults, it may be accompanied by supine hypertension. (6) Panic attacks usually last minutes, occur in specific situations, and are accompanied by choking, palpitations, tremor, heat, and anxiety. Less common causes of spontaneous recurrent vertigo and dizziness include perilymph fistula, superior canal dehiscence, autoimmune inner ear disease, otosclerosis, cardiac arrhythmia, and medication side effects. Neurologists need to venture into otolaryngology, internal medicine, and psychiatry to master the differential diagnosis of recurrent dizziness.

  12. Crows spontaneously exhibit analogical reasoning.

    Science.gov (United States)

    Smirnova, Anna; Zorina, Zoya; Obozova, Tanya; Wasserman, Edward

    2015-01-19

    Analogical reasoning is vital to advanced cognition and behavioral adaptation. Many theorists deem analogical thinking to be uniquely human and to be foundational to categorization, creative problem solving, and scientific discovery. Comparative psychologists have long been interested in the species generality of analogical reasoning, but they initially found it difficult to obtain empirical support for such thinking in nonhuman animals (for pioneering efforts, see [2, 3]). Researchers have since mustered considerable evidence and argument that relational matching-to-sample (RMTS) effectively captures the essence of analogy, in which the relevant logical arguments are presented visually. In RMTS, choice of test pair BB would be correct if the sample pair were AA, whereas choice of test pair EF would be correct if the sample pair were CD. Critically, no items in the correct test pair physically match items in the sample pair, thus demanding that only relational sameness or differentness is available to support accurate choice responding. Initial evidence suggested that only humans and apes can successfully learn RMTS with pairs of sample and test items; however, monkeys have subsequently done so. Here, we report that crows too exhibit relational matching behavior. Even more importantly, crows spontaneously display relational responding without ever having been trained on RMTS; they had only been trained on identity matching-to-sample (IMTS). Such robust and uninstructed relational matching behavior represents the most convincing evidence yet of analogical reasoning in a nonprimate species, as apes alone have spontaneously exhibited RMTS behavior after only IMTS training. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Role of the antidiabetic drugs: Glibenclamide and metformin on the contractility of isolated rat uteri.

    Science.gov (United States)

    Kelany, Mohamed Elsayed; Alqahtani, Saeed; Alkuriji, Afrah; Al-Omar, SulimanYousef

    2016-01-01

    The current investigation has designed to study the role of two antidiabetics, glibenclamide and metformin on the spontaneous uterine contractions in the non-diabetic non-pregnant female rats. The rat uteri were isolated and allocated to two groups: 1)the glibenclamide group: After recording the normal spontaneous uterine contractions, the vehicle (ethanol) and glibenclamide molar concentrations (10(-7), 10(-6) and 10(-5) M) were analyzed on uterine contractions by recording on smoked paper on a rotating kymograph drum, and 2) the metformin group: After recording the normal spontaneous uterine contractions, the metformin concentrations (10(-7), 10(-6) and 10(-5) M) were analyzed on uterine contractions. Responses to the two drugs and vehicle control (ethanol) were recorded for 30 min. Glibenclamide has not significantly effected on the amplitude and frequency of spontaneous contractions of the isolated rat uteri. Metformin also has no significant effect on the amplitude and frequency of spontaneous contractions of the isolated rat uteri. In conclusion, the two oral antidiabetics glibenclamide and metformin have not changed both the amplitude and frequency of spontaneous uterine contractions in the non-pregnant non-diabetic female rats.

  14. Epigenetic Reprogramming of Human Embryonic Stem Cells into Skeletal Muscle Cells and Generation of Contractile Myospheres

    Directory of Open Access Journals (Sweden)

    Sonia Albini

    2013-03-01

    Full Text Available Direct generation of a homogeneous population of skeletal myoblasts from human embryonic stem cells (hESCs and formation of three-dimensional contractile structures for disease modeling in vitro are current challenges in regenerative medicine. Previous studies reported on the generation of myoblasts from ESC-derived embryoid bodies (EB, but not from undifferentiated ESCs, indicating the requirement for mesodermal transition to promote skeletal myogenesis. Here, we show that selective absence of the SWI/SNF component BAF60C (encoded by SMARCD3 confers on hESCs resistance to MyoD-mediated activation of skeletal myogenesis. Forced expression of BAF60C enables MyoD to directly activate skeletal myogenesis in hESCs by instructing MyoD positioning and allowing chromatin remodeling at target genes. BAF60C/MyoD-expressing hESCs are epigenetically committed myogenic progenitors, which bypass the mesodermal requirement and, when cultured as floating clusters, give rise to contractile three-dimensional myospheres composed of skeletal myotubes. These results identify BAF60C as a key epigenetic determinant of hESC commitment to the myogenic lineage and establish the molecular basis for the generation of hESC-derived myospheres exploitable for “disease in a dish” models of muscular physiology and dysfunction.

  15. Scintigraphic measurement of the contractile activity of the gastric antrum using factor analysis

    International Nuclear Information System (INIS)

    Bergmann, H.; Hoebart, J.; Kugi, A.; Stacher, G.; Granser, G.V.

    1990-01-01

    The motor activity of the gastric antrum is difficult to record by manometric means and scintigraphic methods have proved unsatisfactory so far as no consistent relationship between antral contractile activity and gastric emptying rate could be detected. We investigated, using data recorded in 16 healthy human subjects after the ingestion of a semisolid standard meal, whether a newly developed method employing factor analysis would yield more meaningful and reproducible results. Factor analysis was applied to sequential scintigraphic images (3-s frame time) of gastric antrum. The computed factor images and the respective factor curves are representative of distinct dynamic structures of the antrum. From the more or less sinusoidal excursions of the factor curves, which exhibited the 3 cycles per minute frequency characteristic for the stomach, amplitude, frequency and propagation velocity of antral contractions can be calculated. The amplitudes of the factor curves were used to calculate a contraction index. This contraction index was found to be correlated significantly negatively with the gastric half-emptying time of the ingested meal. The employed factor analytical approach thus seems a promising tool to further investigate the role of antral contractility in the process of gastric emptying. (Authors)

  16. Effects of histamine on atrial and ventricular contractility in the canine isovolumic heart.

    Science.gov (United States)

    Vidrio, H; Priola, D V

    1990-03-01

    The effects of intracoronary administration of histamine on atrial and ventricular contractility were determined in a paced canine isovolumic heart preparation. Contractility was assessed by recording the pressure developed in saline-filled balloons placed in each of the four cardiac chambers. At doses above 0.1 mg and up to 100 mg histamine produced dose-related positive inotropic responses in all chambers. These were preceded by transient negative effects. The positive responses were not affected by a combination of H1 and H2 receptor antagonists antazoline and cimetidine but were almost completely abolished by the beta adrenoceptor blocker timolol. The negative responses were uninfluenced by either treatment. It was concluded that, in the canine isovolumic heart not subjected to complicating chronotropic and extracardiac factors, moderate doses of histamine are devoid of inotropic effects. Higher doses do produce myocardial stimulation, not mediated by histamine receptors, but probably due to norepinephrine release. These responses are preceded by transient non-specific depressant effects.

  17. Taurine depresses cardiac contractility and enhances systemic heart glucose utilization in the cuttlefish, Sepia officinalis.

    Science.gov (United States)

    MacCormack, Tyson J; Callaghan, N I; Sykes, A V; Driedzic, W R

    2016-02-01

    Taurine is the most abundant amino acid in the blood of the cuttlefish, Sepia officinalis, where levels can exceed 200 mmol L(-1). In mammals, intracellular taurine modulates cardiac Ca(2+) handling and carbohydrate metabolism at much lower concentrations but it is not clear if it exerts similar actions in cephalopods. Blood Ca(2+) levels are high in cephalopods and we hypothesized that taurine would depress cardiac Ca(2+) flux and modulate contractility in systemic and branchial hearts of cuttlefish. Heart performance was assessed with an in situ perfused systemic heart preparation and contractility was evaluated using isometrically contracting systemic and branchial heart muscle rings. Stroke volume, cardiac output, and Ca(2+) sensitivity were significantly lower in systemic hearts perfused with supplemental taurine (100 mmol L(-1)) than in controls. In muscle ring preparations, taurine impaired relaxation at high contraction frequencies, an effect abolished by supra-physiological Ca(2+) levels. Taurine did not affect oxygen consumption in non-contracting systemic heart muscle, but extracellular glucose utilization was twice that of control preparations. Collectively, our results suggest that extracellular taurine depresses cardiac Ca(2+) flux and potentiates glucose utilization in cuttlefish. Variations in taurine levels may represent an important mechanism for regulating cardiovascular function and metabolism in cephalopods.

  18. Dietary nitrate increases tetanic [Ca2+]i and contractile force in mouse fast-twitch muscle.

    Science.gov (United States)

    Hernández, Andrés; Schiffer, Tomas A; Ivarsson, Niklas; Cheng, Arthur J; Bruton, Joseph D; Lundberg, Jon O; Weitzberg, Eddie; Westerblad, Håkan

    2012-08-01

    Dietary inorganic nitrate has profound effects on health and physiological responses to exercise. Here, we examined if nitrate, in doses readily achievable via a normal diet, could improve Ca(2+) handling and contractile function using fast- and slow-twitch skeletal muscles from C57bl/6 male mice given 1 mm sodium nitrate in water for 7 days. Age matched controls were provided water without added nitrate. In fast-twitch muscle fibres dissected from nitrate treated mice, myoplasmic free [Ca(2+)] was significantly greater than in Control fibres at stimulation frequencies from 20 to 150 Hz, which resulted in a major increase in contractile force at ≤ 50 Hz. At 100 Hz stimulation, the rate of force development was ∼35% faster in the nitrate group. These changes in nitrate treated mice were accompanied by increased expression of the Ca(2+) handling proteins calsequestrin 1 and the dihydropyridine receptor. No changes in force or calsequestrin 1 and dihydropyridine receptor expression were measured in slow-twitch muscles. In conclusion, these results show a striking effect of nitrate supplementation on intracellular Ca(2+) handling in fast-twitch muscle resulting in increased force production. A new mechanism is revealed by which nitrate can exert effects on muscle function with applications to performance and a potential therapeutic role in conditions with muscle weakness.

  19. The RhoGEF TEM4 Regulates Endothelial Cell Migration by Suppressing Actomyosin Contractility.

    Directory of Open Access Journals (Sweden)

    Natalia Mitin

    Full Text Available Persistent cellular migration requires efficient protrusion of the front of the cell, the leading edge where the actin cytoskeleton and cell-substrate adhesions undergo constant rearrangement. Rho family GTPases are essential regulators of the actin cytoskeleton and cell adhesion dynamics. Here, we examined the role of the RhoGEF TEM4, an activator of Rho family GTPases, in regulating cellular migration of endothelial cells. We found that TEM4 promotes the persistence of cellular migration by regulating the architecture of actin stress fibers and cell-substrate adhesions in protruding membranes. Furthermore, we determined that TEM4 regulates cellular migration by signaling to RhoC as suppression of RhoC expression recapitulated the loss-of-TEM4 phenotypes, and RhoC activation was impaired in TEM4-depleted cells. Finally, we showed that TEM4 and RhoC antagonize myosin II-dependent cellular contractility and the suppression of myosin II activity rescued the persistence of cellular migration of TEM4-depleted cells. Our data implicate TEM4 as an essential regulator of the actin cytoskeleton that ensures proper membrane protrusion at the leading edge of migrating cells and efficient cellular migration via suppression of actomyosin contractility.

  20. O-GlcNAcylation, contractile protein modifications and calcium affinity in skeletal muscle

    Directory of Open Access Journals (Sweden)

    Caroline eCieniewski-Bernard

    2014-10-01

    Full Text Available Phosphorylation is recognized as being one of the major post-translational modification involved in the fine modulation of all if not all cellular processes including skeletal muscle contractile activity. However, phosphorylation presents a dynamic and highly regulated interplay with an atypical glycosylation on intracellular proteins, the O-GlcNAcylation. Akin to phosphorylation, O-GlcNAcylation is also involved in the physiopathology of several acquired diseases, such as muscle insulin resistance in diabetes or muscle atrophy. Recent data underline that the interplay between phosphorylation and O-GlcNAcylation acts as a modulator of skeletal muscle contractile activity. In particular, the O-GlcNAcylation level of the phosphoprotein MLC2 seems to be crucial in the modulation of the calcium activation properties, and should be responsible of changes in calcium properties observed in atrophy. Moreover, since several key structural proteins are O-GlcNAc-modified, and because of the localization of the enzymes involved in the O-GlcNAcylation/de-O-GlcNAcylation process to the nodal Z disk, a role of O-GlcNAcylation in the modulation of the sarcomeric structure should be considered.

  1. Role of UCP3 in state 4 respiration during contractile activity-induced mitochondrial biogenesis.

    Science.gov (United States)

    Ljubicic, Vladimir; Adhihetty, Peter J; Hood, David A

    2004-09-01

    In an effort to better characterize uncoupling protein-3 (UCP3) function in skeletal muscle, we assessed basal UCP3 protein content in rat intermyofibrillar (IMF) and subsarcolemmal (SS) mitochondrial subfractions in conjunction with measurements of state 4 respiration. UCP3 content was 1.3-fold (P respiration was 2.6-fold greater (P respiration by approximately 40% (P respiration in IMF mitochondria only. We used chronic electrical stimulation (3 h/day for 7 days) to investigate the relationship between changes in UCP3 protein expression and alterations in state 4 respiration during contractile activity-induced mitochondrial biogenesis. UCP3 content was increased by 1.9- and 2.3-fold in IMF and SS mitochondria, respectively, which exceeded the concurrent 40% (P respiration by 1.4-fold (P respiration in IMF mitochondria, which was independent of the induced twofold difference in UCP3 content due to chronic contractile activity. Thus modifications in UCP3 function are more important than changes in UCP3 expression in modifying state 4 respiration. This effect is evident in IMF but not SS mitochondria. We conclude that UCP3 at physiological concentrations accounts for a significant portion of state 4 respiration in both IMF and SS mitochondria, with the contribution being greater in the IMF subfraction. In addition, the contradiction between human and rat training studies with respect to UCP3 protein expression may partly be explained by the greater than twofold difference in mitochondrial UCP3 content between rat and human skeletal muscle.

  2. Evolutionarily conserved sites in yeast tropomyosin function in cell polarity, transport and contractile ring formation

    Directory of Open Access Journals (Sweden)

    Susanne Cranz-Mileva

    2015-08-01

    Full Text Available Tropomyosin is a coiled-coil protein that binds and regulates actin filaments. The tropomyosin gene in Schizosaccharomyces pombe, cdc8, is required for formation of actin cables, contractile rings, and polar localization of actin patches. The roles of conserved residues were investigated in gene replacement mutants. The work validates an evolution-based approach to identify tropomyosin functions in living cells and sites of potential interactions with other proteins. A cdc8 mutant with near-normal actin affinity affects patch polarization and vacuole fusion, possibly by affecting Myo52p, a class V myosin, function. The presence of labile residual cell attachments suggests a delay in completion of cell division and redistribution of cell patches following cytokinesis. Another mutant with a mild phenotype is synthetic negative with GFP-fimbrin, inferring involvement of the mutated tropomyosin sites in interaction between the two proteins. Proteins that assemble in the contractile ring region before actin do so in a mutant cdc8 strain that cannot assemble condensed actin rings, yet some cells can divide. Of general significance, LifeAct-GFP negatively affects the actin cytoskeleton, indicating caution in its use as a biomarker for actin filaments.

  3. Natural Antioxidant-Isoliquiritigenin Ameliorates Contractile Dysfunction of Hypoxic Cardiomyocytes via AMPK Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Xiaoyu Zhang

    2013-01-01

    Full Text Available Isoliquiritigenin (ISL, a simple chalcone-type flavonoid, is derived from licorice compounds and is mainly present in foods, beverages, and tobacco. Reactive oxygen species (ROS is a critical factor involved in modulating cardiac stress response signaling during ischemia and reperfusion. We hypothesize that ISL as a natural antioxidant may protect heart against ischemic injury via modulating cellular redox status and regulating cardioprotective signaling pathways. The fluorescent probe H2DCFDA was used to measure the level of intracellular ROS. The glucose uptake was determined by 2-deoxy-D-glucose-3H accumulation. The IonOptix System measured the contractile function of isolated cardiomyocytes. The results demonstrated that ISL treatment markedly ameliorated cardiomyocytes contractile dysfunction caused by hypoxia. ISL significantly stimulated cardioprotective signaling, AMP-activated protein kinase (AMPK, and extracellular signal-regulated kinase (ERK signaling pathways. The ROS fluorescent probe H2DCFDA determination indicated that ISL significantly reduced cardiac ROS level during hypoxia/reoxygenation. Moreover, ISL reduced the mitochondrial potential (Δψ of isolated mouse cardiomyocytes. Taken together, ISL as a natural antioxidant demonstrated the cardioprotection against ischemic injury that may attribute to the activation of AMPK and ERK signaling pathways and balance of cellular redox status.

  4. Predictive K-PLSR myocardial contractility modeling with phase contrast MR velocity mapping.

    Science.gov (United States)

    Lee, Su-Lin; Wu, Qian; Huntbatch, Andrew; Yang, Guang-Zhong

    2007-01-01

    With the increasing versatility of CMR, further understanding of intrinsic contractility of the myocardium can be achieved by performing subject-specific modeling by integrating structural and functional information available. The recent introduction of the virtual tagging framework allows for visualization of the localized deformation of the myocardium based on phase contrast myocardial velocity mapping. The purpose of this study is to examine the use of a non-linear, Kernel-Partial Least Squares Regression (K-PLSR) predictive motion modeling scheme for the virtual tagging framework. The method allows for the derivation of a compact non-linear deformation model such that the entire deformation field can be predicted by a limited number of control points. When applied to virtual tagging, the technique can be used to predictively guide the mesh refinement based on the motion of the coarse grid, thus greatly reducing the search space and increasing the convergence speed of the algorithm. The effectiveness and numerical accuracy of the proposed technique are assessed with both numerically simulated data sets and in vivo phase contrast CMR velocity mapping from a group of 7 subjects. The technique presented has a distinct advantage over the conventional mesh refinement scheme and brings CMR myocardial contractility analysis closer to routine clinical practice.

  5. Cortical contractility triggers a stochastic switch to fast amoeboid cell motility.

    Science.gov (United States)

    Ruprecht, Verena; Wieser, Stefan; Callan-Jones, Andrew; Smutny, Michael; Morita, Hitoshi; Sako, Keisuke; Barone, Vanessa; Ritsch-Marte, Monika; Sixt, Michael; Voituriez, Raphaël; Heisenberg, Carl-Philipp

    2015-02-12

    3D amoeboid cell migration is central to many developmental and disease-related processes such as cancer metastasis. Here, we identify a unique prototypic amoeboid cell migration mode in early zebrafish embryos, termed stable-bleb migration. Stable-bleb cells display an invariant polarized balloon-like shape with exceptional migration speed and persistence. Progenitor cells can be reversibly transformed into stable-bleb cells irrespective of their primary fate and motile characteristics by increasing myosin II activity through biochemical or mechanical stimuli. Using a combination of theory and experiments, we show that, in stable-bleb cells, cortical contractility fluctuations trigger a stochastic switch into amoeboid motility, and a positive feedback between cortical flows and gradients in contractility maintains stable-bleb cell polarization. We further show that rearward cortical flows drive stable-bleb cell migration in various adhesive and non-adhesive environments, unraveling a highly versatile amoeboid migration phenotype. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Oxidative Stress in Hypertensive Patients Induces an Increased Contractility in Vein Grafts Independent of Endothelial Function

    Directory of Open Access Journals (Sweden)

    Claudio Joo Turoni

    2011-01-01

    Full Text Available Objective. To evaluate the impact of oxidative stress on vascular reactivity to vasoconstrictors and on nitric oxide (NO bioavailability in saphenous vein (SV graft with endothelial dysfunction from hypertensive patients (HT. Methods. Endothelial function, vascular reactivity, oxidative state, nitrites and NO release were studied in isolated SV rings from HT and normotensive patients (NT. Only rings with endothelial dysfunction were used. Results. HT rings presented a hyperreactivity to vasoconstrictors that was reverted by diphenylene iodonium (DPI. In NT, no effect of DPI was obtained, but Nω-nitro-L-arginine methyl ester (L-NAME increased the contractile response. NO was present in SV rings without endothelial function. Nitrites were higher in NT than in HT (1066.1 ± 86.3 pmol/mg; n=11 versus 487.8 ± 51.6; n=23; P<0.01 and inhibited by nNOS inhibitor. L-arginine reversed this effect. Antioxidant agents increased nitrites and NO contents only in HT. The anti-nNOS-stained area by immunohistochemistry was higher in NT than HT. HT showed an elevation of oxidative state. Conclusions. Extraendothelial NO counter-regulates contractility in SV. However, this action could be altered in hypertensive situations by an increased oxidative stress or a decreased ability of nNOS to produce NO. Further studies should be performed to evaluate the implication of these results in graft patency rates.

  7. Effects of clenbuterol on contractility and Ca2+ homeostasis of isolated rat ventricular myocytes

    Science.gov (United States)

    Siedlecka, U.; Arora, M.; Kolettis, T.; Soppa, G. K. R.; Lee, J.; Stagg, M. A.; Harding, S. E.; Yacoub, M. H.; Terracciano, C. M. N.

    2008-01-01

    Clenbuterol, a compound classified as a β2-adrenoceptor (AR) agonist, has been employed in combination with left ventricular assist devices (LVADs) to treat patients with severe heart failure. Previous studies have shown that chronic administration of clenbuterol affects cardiac excitation-contraction coupling. However, the acute effects of clenbuterol and the signaling pathway involved remain undefined. We investigated the acute effects of clenbuterol on isolated ventricular myocyte sarcomere shortening, Ca2+ transients, and L-type Ca2+ current and compared these effects to two other clinically used β2-AR agonists: fenoterol and salbutamol. Clenbuterol (30 μM) produced a negative inotropic response, whereas fenoterol showed a positive inotropic response. Salbutamol had no significant effects. Clenbuterol reduced Ca2+ transient amplitude and L-type Ca2+ current. Selective β1-AR blockade did not affect the action of clenbuterol on sarcomere shortening but significantly reduced contractility in the presence of fenoterol and salbutamol (P clenbuterol. In addition, overexpression of inhibitory G protein (Gi) by adenoviral transfection induced a stronger clenbuterol-mediated negative inotropic effect, suggesting the involvement of the Gi protein. We conclude that clenbuterol does not increase and, at high concentrations, significantly depresses contractility of isolated ventricular myocytes, an effect not seen with fenoterol or salbutamol. In its negative inotropism, clenbuterol predominantly acts through Gi, and the consequent downstream signaling pathways activation may explain the beneficial effects observed during chronic administration of clenbuterol in patients treated with LVADs. PMID:18775853

  8. A stepwise procedure to test contractility and susceptibility to injury for the rodent quadriceps muscle

    Directory of Open Access Journals (Sweden)

    Stephen J.P. Pratt

    2014-07-01

    Full Text Available In patients with muscle injury or muscle disease, assessment of muscle damage is typically limited to clinical signs, such as tenderness, strength, range of motion, and more recently, imaging studies.  Biological markers can also be used in measuring muscle injury, such as increased creatine kinase levels in the blood, but these are not always correlated with loss in muscle function (i.e. loss of force production.  This is even true of histological findings from animals, which provide a “direct measure” of damage, but do not account for loss of function.  The most comprehensive measure of the overall health of the muscle is contractile force.  To date, animal models testing contractile force have been limited to the muscle groups moving the ankle.  Here we describe an in vivo animal model for the quadriceps, with abilities to measure torque, produce a reliable muscle injury, and follow muscle recovery within the same animal over time.  We also describe a second model used for direct measurement of force from an isolated quadriceps muscle in situ. 

  9. Izalpinin from fruits of Alpinia oxyphylla with antagonistic activity against the rat bladder contractility.

    Science.gov (United States)

    Yuan, Yuan; Tan, Yin-Feng; Xu, Peng; Li, Hailong; Li, Yong-Hui; Chen, Wen-Ya; Zhang, Jun-Qing; Chen, Feng; Huang, Guo-Jun

    2014-01-01

    Alpinia oxyphylla (Zingiberaceae), an herbaceous perennial plant, its capsular fruit is commonly used in traditional Chinese medicine for the treatment of different urinary incontinence symptoms including frequency, urgency and nocturia. These symptoms are similar to the overactive bladder syndrome. In our lab, we found that the 95% ethanol extract of the capsular fruits exhibited significant anti-muscarinic activity. Some constituents in capsular fruits including flavonoids (e.g., izalpinin and tectochrysin), diarylheptanoids (e.g., yakuchinone A and yakuchinone B) and sesquiterpenes (e.g., nootkatone), are regarded as representative chemicals with putative pharmacological activities. This study aimed to evaluate the in vitro antagonistic actions of izalpinin on carbachol-induced contraction of the rat detrusor muscle. In vitro inhibition of rat detrusor contractile response to carbachol was used to study the functional activity of izalpinin. The isolated detrusor strips of rats were mounted in organ baths containing oxygenated Krebs' solution. The cumulative consecutive concentration-response curves to carbachol-evoked contractions in strips of rat bladder were obtained. Carbachol induced concentration-dependent contractions of isolated rat bladder detrusor strips. The vehicle DMSO had no impact on the contraction response. The contraction effects were concentration-dependently antagonized by izalpinin, with a mean EC50 value of 0.35 µM. The corresponding cumulative agonist concentration-response curves shifted right-ward. Izalpinin exhibits inhibitory role of muscarinic receptor-related detrusor contractile activity, and it may be a promising lead compound to treat overactive bladder.

  10. PPARγ Ligands Regulate Noncontractile and Contractile Functions of Airway Smooth Muscle: Implications for Asthma Therapy

    Directory of Open Access Journals (Sweden)

    Chantal Donovan

    2012-01-01

    Full Text Available In asthma, the increase in airway smooth muscle (ASM can contribute to inflammation, airway wall remodeling and airway hyperresponsiveness (AHR. Targetting peroxisome proliferator-activated receptor γ (PPARγ, a receptor upregulated in ASM in asthmatic airways, may provide a novel approach to regulate these contributions. This review summarises experimental evidence that PPARγ ligands, such as rosiglitazone (RGZ and pioglitazone (PGZ, inhibit proliferation and inflammatory cytokine production from ASM in vitro. In addition, inhaled administration of these ligands reduces inflammatory cell infiltration and airway remodelling in mouse models of allergen-induced airways disease. PPARγ ligands can also regulate ASM contractility, with acute treatment eliciting relaxation of mouse trachea in vitro through a PPARγ-independent mechanism. Chronic treatment can protect against the loss of bronchodilator sensitivity to β2-adrenoceptor agonists and inhibit the development of AHR associated with exposure to nicotine in utero or following allergen challenge. Of particular interest, a small clinical trial has shown that oral RGZ treatment improves lung function in smokers with asthma, a group that is generally unresponsive to conventional steroid treatment. These combined findings support further investigation of the potential for PPARγ agonists to target the noncontractile and contractile functions of ASM to improve outcomes for patients with poorly controlled asthma.

  11. Baseplate assembly of phage Mu: Defining the conserved core components of contractile-tailed phages and related bacterial systems.

    Science.gov (United States)

    Büttner, Carina R; Wu, Yingzhou; Maxwell, Karen L; Davidson, Alan R

    2016-09-06

    Contractile phage tails are powerful cell puncturing nanomachines that have been co-opted by bacteria for self-defense against both bacteria and eukaryotic cells. The tail of phage T4 has long served as the paradigm for understanding contractile tail-like systems despite its greater complexity compared with other contractile-tailed phages. Here, we present a detailed investigation of the assembly of a "simple" contractile-tailed phage baseplate, that of Escherichia coli phage Mu. By coexpressing various combinations of putative Mu baseplate proteins, we defined the required components of this baseplate and delineated its assembly pathway. We show that the Mu baseplate is constructed through the independent assembly of wedges that are organized around a central hub complex. The Mu wedges are comprised of only three protein subunits rather than the seven found in the equivalent structure in T4. Through extensive bioinformatic analyses, we found that homologs of the essential components of the Mu baseplate can be identified in the majority of contractile-tailed phages and prophages. No T4-like prophages were identified. The conserved simple baseplate components were also found in contractile tail-derived bacterial apparatuses, such as type VI secretion systems, Photorhabdus virulence cassettes, and R-type tailocins. Our work highlights the evolutionary connections and similarities in the biochemical behavior of phage Mu wedge components and the TssF and TssG proteins of the type VI secretion system. In addition, we demonstrate the importance of the Mu baseplate as a model system for understanding bacterial phage tail-derived systems.

  12. Effects of dihydropyridines on tension and calcium-45 influx in isolated mesenteric resistance vessels from spontaneously hypertensive and normotensive rats

    International Nuclear Information System (INIS)

    Cauvin, C.; Hwang, O.; Yamamoto, M.; van Breemen, C.

    1987-01-01

    Contractile tension responses to norepinephrine and depolarizing potassium (80 mM K+), as well as calcium-45 influx stimulated by these agents, were studied in isolated mesenteric resistance vessels (each 100 microM internal diameter) from spontaneously hypertensive rats (SHRs) and from normotensive Wistar Kyoto rats (WKYs). Inhibitory effects of 2 dihydropyridine Ca++ antagonists, PN 200-110 (isradipine) and nisoldipine, on these parameters were also determined. Contractile responses to 80 mM K+ were inhibited by both Ca++ antagonists with the same potency and efficacy in SHR compared with WKY vessels (PN 200-110 IC50 = 2.8 +/- 1.3 X 10(-8) M in SHRs and 2.5 +/- 1.5 X 10(-8) M in WKYs; nisoldipine IC50 = 1.1 +/- 0.4 X 10(-8) M in SHRs and 1.2 +/- 0.9 X 10(-8) M in WKYs). However, contractile responses to norepinephrine (10(-4) M) were inhibited less potently by nisoldipine in SHR vessels (IC50 = 2.2 +/- 0.3 X 10(-9) M) compared with WKY vessels (IC50 = 1.6 +/- 0.6 X 10(-10) M). Similarly, PN 200-110 tended to be less (but not significantly less) potent in SHR vessels (IC50 = 3.3 +/- 1.8 X 10(-8) M) than in WKY vessels (IC50 = 3.4 +/- 0.9 X 10(-9) M); its efficacy was significantly depressed in the SHR vessels (by approximately 20%). When norepinephrine-stimulated calcium-45 influx was determined in the presence of these Ca++ antagonists, a similar profile emerged with respect to a comparison of SHR and WKY vessels. These results support a previously hypothesized alteration in receptor-activated Ca++ influx pathways in SHR mesenteric resistance vessels

  13. Stabiliteit spontane taal bij chronische milde afasie

    NARCIS (Netherlands)

    Wolthuis, Nienke; Mendez Orellana, Carolina; Nouwens, Femke; Jonkers, Roel; Visch-Brink, Evy; Bastiaanse, Roelien

    2014-01-01

    In aphasia, an analysis of spontaneous speech provides opportunities to establish the linguistic and communicative abilities, to create suitable therapy plans and to measure language progress. The current study investigated the stability of spontaneous speech within an interview of ten mild aphasic

  14. Spontaneously broken abelian gauge invariant supersymmetric model

    International Nuclear Information System (INIS)

    Mainland, G.B.; Tanaka, K.

    A model is presented that is invariant under an Abelian gauge transformation and a modified supersymmetry transformation. This model is broken spontaneously, and the interplay between symmetry breaking, Goldstone particles, and mass breaking is studied. In the present model, spontaneously breaking the Abelian symmetry of the vacuum restores the invariance of the vacuum under a modified supersymmetry transformation. (U.S.)

  15. Spontaneous Achilles tendon rupture in alkaptonuria | Mohammed ...

    African Journals Online (AJOL)

    Spontaneous Achilles tendon ruptures are uncommon. We present a 46-year-old man with spontaneous Achilles tendon rupture due to ochronosis. To our knowledge, this has not been previously reported in Sudan literature. The tendon of the reported patient healed well after debridement and primary repairs.

  16. Spontaneous rupture of choledochal cyst: case report

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Ho Seob; Nam, Kyung Jin; Lee, Jin Hwa; Kim, Chan Sung; Choi, Jong Cheol; Oh, Jong Young [Dong-a University College of Medicine, Pusan (Korea, Republic of)

    2002-11-01

    Spontaneous rupture of a choledochal cyst leading to biliary peritonitis is a rare complication which can be fatal if not promptly diagnosed. The authors report the ultrasound and CT findings of two cases of spontaneous choledochal cystic rupture and the biliary peritonitis which ensued.

  17. Spontaneity and Equilibrium II: Multireaction Systems

    Science.gov (United States)

    Raff, Lionel M.

    2014-01-01

    The thermodynamic criteria for spontaneity and equilibrium in multireaction systems are developed and discussed. When N reactions are occurring simultaneously, it is shown that G and A will depend upon N independent reaction coordinates, ?a (a = 1,2, ..., N), in addition to T and p for G or T and V for A. The general criteria for spontaneity and…

  18. Endothelin-1 and endothelin-2 initiate and maintain contractile responses by different mechanisms in rat mesenteric and cerebral arteries

    DEFF Research Database (Denmark)

    Compeer, M. G.; Janssen, G. M. J.; De Mey, J. G. R.

    2013-01-01

    , but relaxed ET-1-induced contractions in MRA. A PLC inhibitor prevented contractile responses to ET-1 and ET-2 in MRA and BA, and relaxed ET-1- and ET-2-induced responses in MRA and ET-1 effects in BA. A Rho-kinase inhibitor did not modify sensitivity, maximum and maintenance of responses to both peptides...... in both arteries but relaxed ET-2, but not ET-1, effects in MRA and ET-1 effects in BA. Conclusions and ImplicationsPLC played a key role in arterial contractile responses to ETs, but ET-1 and ET-2 initiated and maintained vasoconstriction through different mechanisms, and these differed between MRA...

  19. Alterations in serotonin receptor-induced contractility of bovine lateral saphenous vein in cattle grazing endophyte-infected tall fescue.

    Science.gov (United States)

    Klotz, J L; Brown, K R; Xue, Y; Matthews, J C; Boling, J A; Burris, W R; Bush, L P; Strickland, J R

    2012-02-01

    As part of a 2-yr study documenting the physiologic impact of grazing endophyte-infected tall fescue on growing cattle, 2 experiments were conducted to characterize and evaluate effects of grazing 2 levels of toxic endophyte-infected tall fescue pastures on vascular contractility and serotonin receptors. Experiment 1 examined vasoconstrictive activities of 5-hydroxytryptamine (5HT), α-methylserotonin (ME5HT; a 5HT(2) receptor agonist), d-lysergic acid (LSA), and ergovaline (ERV) on lateral saphenous veins collected from steers immediately removed from a high-endophyte-infected tall fescue pasture (HE) or a low-endophyte-infected mixed-grass (LE) pasture. Using the same pastures, Exp. 2 evaluated effects of grazing 2 levels of toxic endophyte-infected tall fescue on vasoconstrictive activities of (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), BW 723C86 (BW7), CGS-12066A (CGS), and 5-carboxamidotryptamine hemiethanolate maleate (5CT), agonists for 5HT(2A),( 2B), 5HT(1B), and 5HT(7) receptors, respectively. One-half of the steers in Exp. 2 were slaughtered immediately after removal from pasture, and the other one-half were fed finishing diets for >91 d before slaughter. For Exp. 1, maximal contractile intensities were greater (P grazing LE pastures than HE pastures for 5HT (73.3 vs. 48.9 ± 2.1%), ME5HT (52.7 vs. 24.9 ± 1.5%), and ERV (65.7 vs. 49.1 ± 2.6%). Onset of contractile response did not differ for 5HT (P = 0.26) and ERV (P = 0.93), but onset of ME5HT contraction was not initiated (P grazing steers. For Exp. 2, maximal contractile intensities achieved with DOI were 35% less (P grazing HE pastures. Contractile response to CGS did not differ between pasture groups, and there was an absence of contractile response to BW7 in both groups. There were no differences between endophyte content in contractile responses after animals were finished for >91 d. Experiment 1 demonstrated that grazing of HE pastures for 89 to 105 d induces

  20. Early pregnancy angiogenic markers and spontaneous abortion

    DEFF Research Database (Denmark)

    Andersen, Louise B; Dechend, Ralf; Karumanchi, S Ananth

    2016-01-01

    BACKGROUND: Spontaneous abortion is the most commonly observed adverse pregnancy outcome. The angiogenic factors soluble Fms-like kinase 1 and placental growth factor are critical for normal pregnancy and may be associated to spontaneous abortion. OBJECTIVE: We investigated the association between...... maternal serum concentrations of soluble Fms-like kinase 1 and placental growth factor, and subsequent spontaneous abortion. STUDY DESIGN: In the prospective observational Odense Child Cohort, 1676 pregnant women donated serum in early pregnancy, gestational week ..., interquartile range 71-103). Concentrations of soluble Fms-like kinase 1 and placental growth factor were determined with novel automated assays. Spontaneous abortion was defined as complete or incomplete spontaneous abortion, missed abortion, or blighted ovum

  1. The (perceived) meaning of spontaneous thoughts.

    Science.gov (United States)

    Morewedge, Carey K; Giblin, Colleen E; Norton, Michael I

    2014-08-01

    Spontaneous thoughts, the output of a broad category of uncontrolled and inaccessible higher order mental processes, arise frequently in everyday life. The seeming randomness by which spontaneous thoughts arise might give people good reason to dismiss them as meaningless. We suggest that it is precisely the lack of control over and access to the processes by which they arise that leads people to perceive spontaneous thoughts as revealing meaningful self-insight. Consequently, spontaneous thoughts potently influence judgment. A series of experiments provides evidence supporting two hypotheses. First, we hypothesize that the more a thought is perceived to be spontaneous, the more it is perceived to provide meaningful self-insight. Participants perceived more spontaneous kinds of thought (e.g., intuition) to reveal greater self-insight than did more controlled kinds of thought in Study 1 (e.g., deliberation). In Studies 2 and 3, participants perceived thoughts with the same content and target to reveal greater self-insight when spontaneously rather than deliberately generated (i.e., childhood memories and impressions formed). Second, we hypothesize that the greater self-insight attributed to thoughts that are (perceived to be) spontaneous leads those thoughts to more potently influence judgment. Participants felt more sexually attracted to an attractive person whom they thought of spontaneously than deliberately in Study 4, and reported their commitment to a current romantic relationship would be more affected by the spontaneous rather than deliberate recollection of a good or bad experience with their romantic partner in Study 5. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  2. Fullerenol C60(OH)24 nanoparticles decrease relaxing effects of dimethyl sulfoxide on rat uterus spontaneous contraction

    International Nuclear Information System (INIS)

    Slavic, Marija; Djordjevic, Aleksandar; Radojicic, Ratko; Milovanovic, Slobodan; Orescanin-Dusic, Zorana; Rakocevic, Zlatko; Spasic, Mihajlo B.; Blagojevic, Dusko

    2013-01-01

    Dimethyl sulfoxide (DMSO) is a widely used solvent and cryoprotectant that can cause impaired blood flow, reduction in intracranial pressure, tissue edema, inflammatory reactions, inhibition of vascular smooth muscle cell migration and proliferation, processes which can lead to atherosclerosis of the coronary, peripheral and cerebral circulation. Although the adverse effects are rare when DMSO is administered in clinically established concentrations, there is no safe antagonist for an overdose. In this work, we treated isolated spontaneous and calcium-induced contractile active rat uteri (Wistar, virgo intacta), with DMSO and fullerenol C 60 (OH) 24 nanoparticle (FNP) in DMSO. FNP is a water-soluble derivative of fullerene C 60 . Its size is a 1.1 nm in diameter and is a very promising candidate for a drug carrier in nanomedicine. FNP also displays free radical scavenging activity. DMSO decreased both spontaneous and calcium-induced contractions. In contrast, FNP only decreased spontaneous contraction. FNP decreased copper–zinc superoxide dismutase activity and prevented the DMSO-induced increase in glutathione reductase activity. Atomic force microscopy detected that FNP aggregated with calcium ions. Our results indicate that FNP has properties that make it a good candidate to be a modulator of DMSO activity which could minimize side effects of the latter.

  3. Fullerenol C60(OH)24 nanoparticles decrease relaxing effects of dimethyl sulfoxide on rat uterus spontaneous contraction

    Science.gov (United States)

    Slavic, Marija; Djordjevic, Aleksandar; Radojicic, Ratko; Milovanovic, Slobodan; Orescanin-Dusic, Zorana; Rakocevic, Zlatko; Spasic, Mihajlo B.; Blagojevic, Dusko

    2013-05-01

    Dimethyl sulfoxide (DMSO) is a widely used solvent and cryoprotectant that can cause impaired blood flow, reduction in intracranial pressure, tissue edema, inflammatory reactions, inhibition of vascular smooth muscle cell migration and proliferation, processes which can lead to atherosclerosis of the coronary, peripheral and cerebral circulation. Although the adverse effects are rare when DMSO is administered in clinically established concentrations, there is no safe antagonist for an overdose. In this work, we treated isolated spontaneous and calcium-induced contractile active rat uteri (Wistar, virgo intacta), with DMSO and fullerenol C60(OH)24 nanoparticle (FNP) in DMSO. FNP is a water-soluble derivative of fullerene C60. Its size is a 1.1 nm in diameter and is a very promising candidate for a drug carrier in nanomedicine. FNP also displays free radical scavenging activity. DMSO decreased both spontaneous and calcium-induced contractions. In contrast, FNP only decreased spontaneous contraction. FNP decreased copper-zinc superoxide dismutase activity and prevented the DMSO-induced increase in glutathione reductase activity. Atomic force microscopy detected that FNP aggregated with calcium ions. Our results indicate that FNP has properties that make it a good candidate to be a modulator of DMSO activity which could minimize side effects of the latter.

  4. Retigabine diminishes the effects of acetylcholine, adrenaline and adrenergic agonists on the spontaneous activity of guinea pig smooth muscle strips in vitro.

    Science.gov (United States)

    Apostolova, Elisaveta; Zagorchev, Plamen; Kokova, Vesela; Peychev, Lyudmil

    2017-03-01

    The aim of this study is to evaluate the effect of retigabine on the smooth muscle response to acetylcholine, adrenaline, α-and β-adrenoceptor agonists. We studied the change in the spontaneous smooth muscle contraction of guinea pig gastric corpus strips before and after 20-min treatment with 2μM retigabine. We also evaluated the effect of retigabine on the smooth muscle response to 10μM acetylcholine, 1 and 10μM adrenaline, 1μM methoxamine, 0.1μM p-iodoclonidine and 10μM isoproterenol. We observed a significant reduction in the effects of all studied mediators and agonists when they were added to organ baths in the presence of retigabine. Retigabine diminished the effect of acetylcholine on the spontaneous smooth muscle activity. The effect was fully antagonized by XE-991 (Kv7 channel blocker), which supports our hypothesis about the role of KCNQ channels in the registered changes. The increase in the contraction force after adding of 1μM adrenaline, methoxamine, and 0.1μM p-iodoclonidine was also significantly smaller in presence of retigabine. However, comparing the effect of 10μM adrenaline on the contractility before and after treatment with retigabine, we observed increased contractility when retigabine was present in the organ baths. A possible explanation for the observed diminished effects of mediators and receptor agonists is that the effect of retigabine on smooth muscle contractility is complex. The membrane hyperpolarization, the interaction between Kv7 channels and adrenoceptors, and the influence on signaling pathways may contribute to the summary smooth muscle response. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Glucuronidated Quercetin Lowers Blood Pressure in Spontaneously Hypertensive Rats via Deconjugation

    Science.gov (United States)

    Galindo, Pilar; Rodriguez-Gómez, Isabel; González-Manzano, Susana; Dueñas, Montserrat; Jiménez, Rosario; Menéndez, Carmen; Vargas, Félix; Tamargo, Juan; Santos-Buelga, Celestino; Pérez-Vizcaíno, Francisco; Duarte, Juan

    2012-01-01

    Background Chronic oral quercetin reduces blood pressure and restores endothelial dysfunction in hypertensive animals. However, quercetin (aglycone) is usually not present in plasma, because it is rapidly metabolized into conjugated, mostly inactive, metabolites. The aim of the study is to analyze whether deconjugation of these metabolites is involved in the blood pressure lowering effect of quercetin. Methodology/Principal Findings We have analyzed the effects on blood pressure and vascular function in vitro of the conjugated metabolites of quercetin (quercetin-3-glucuronide, Q3GA; isorhamnetin-3-glucuronide, I3GA; and quercetin-3′-sulfate, Q3'S) in spontaneously hypertensive rats (SHR). Q3GA and I3GA (1 mg/kg i.v.), but not Q3'S, progressively reduced mean blood pressure (MBP), measured in conscious SHR. The hypotensive effect of Q3GA was abolished in SHR treated with the specific inhibitor of β-glucuronidase, saccharic acid 1,4-lactone (SAL, 10 mg/ml). In mesenteric arteries, unlike quercetin, Q3GA had no inhibitory effect in the contractile response to phenylephrine after 30 min of incubation. However, after 1 hour of incubation Q3GA strongly reduced this contractile response and this effect was prevented by SAL. Oral administration of quercetin (10 mg/Kg) induced a progressive decrease in MBP, which was also suppressed by SAL. Conclusions Conjugated metabolites are involved in the in vivo antihypertensive effect of quercetin, acting as molecules for the plasmatic transport of quercetin to the target tissues. Quercetin released from its glucuronidated metabolites could be responsible for its vasorelaxant and hypotensive effect. PMID:22427863

  6. Acute exposure to lead increases myocardial contractility independent of hypertension development

    Energy Technology Data Exchange (ETDEWEB)

    Fioresi, M. [Programa de Pós-Graduação em Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Departamento de Enfermagem, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Furieri, L.B.; Simões, M.R.; Ribeiro, R.F. Junior; Meira, E.F.; Fernandes, A.A.; Stefanon, I. [Programa de Pós-Graduação em Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Vassallo, D.V. [Programa de Pós-Graduação em Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Centro de Ciências da Saúde de Vitória, Escola Superior de Ciências da Santa Casa de Misericórdia de Vitória, Vitória, ES (Brazil)

    2013-02-01

    We studied the effects of the acute administration of small doses of lead over time on hemodynamic parameters in anesthetized rats to determine if myocardial contractility changes are dependent or not on the development of hypertension. Male Wistar rats received 320 µg/kg lead acetate iv once, and their hemodynamic parameters were measured for 2 h. Cardiac contractility was evaluated in vitro using left ventricular papillary muscles as were Na{sup +},K{sup +}-ATPase and myosin Ca{sup 2+}-ATPase activities. Lead increased left- (control: 112 ± 3.7 vs lead: 129 ± 3.2 mmHg) and right-ventricular systolic pressures (control: 28 ± 1.2 vs lead: 34 ± 1.2 mmHg) significantly without modifying heart rate. Papillary muscles were exposed to 8 µM lead acetate and evaluated 60 min later. Isometric contractions increased (control: 0.546 ± 0.07 vs lead: 0.608 ± 0.06 g/mg) and time to peak tension decreased (control: 268 ± 13 vs lead: 227 ± 5.58 ms), but relaxation time was unchanged. Post-pause potentiation was similar between groups (n = 6 per group), suggesting no change in sarcoplasmic reticulum activity, evaluated indirectly by this protocol. After 1-h exposure to lead acetate, the papillary muscles became hyperactive in response to a β-adrenergic agonist (10 µM isoproterenol). In addition, post-rest contractions decreased, suggesting a reduction in sarcolemmal calcium influx. The heart samples treated with 8 µM lead acetate presented increased Na{sup +},K{sup +}-ATPase (approximately 140%, P < 0.05 for control vs lead) and myosin ATPase (approximately 30%, P < 0.05 for control vs lead) activity. Our results indicated that acute exposure to low lead concentrations produces direct positive inotropic and lusitropic effects on myocardial contractility and increases the right and left ventricular systolic pressure, thus potentially contributing to the early development of hypertension.

  7. Contractile function and motor unit firing rates of the human hamstrings.

    Science.gov (United States)

    Kirk, Eric A; Rice, Charles L

    2017-01-01

    Neuromuscular properties of the lower limb in health, aging, and disease are well described for major lower limb muscles comprising the quadriceps, triceps surae, and dorsiflexors, with the notable exception of the posterior thigh (hamstrings). The purpose of this study was to further characterize major muscles of the lower limb by comprehensively exploring contractile properties in relation to spinal motor neuron output expressed as motor unit firing rates (MUFRs) in the hamstrings of 11 (26.5 ± 3.8) young men. Maximal isometric voluntary contraction (MVC), voluntary activation, stimulated contractile properties including a force-frequency relationship, and MUFRs from submaximal to maximal voluntary contractile intensities were assessed in the hamstrings. Strength and MUFRs were assessed at two presumably different muscle lengths by varying the knee joint angles (90° and 160°). Knee flexion MVCs were 60-70% greater in the extended position (160°). The frequency required to elicit 50% of maximum tetanic torque was 16-17 Hz. Mean MUFRs at 25-50% MVC were 9-31% less in the biceps femoris compared with the semimembranosus-semitendinosus group. Knee joint angle (muscle length) influenced MUFRs such that mean MUFRs were greater in the shortened (90°) position at 50% and 100% MVC. Compared with previous reports, mean maximal MUFRs in the hamstrings are greater than those in the quadriceps and triceps surae and somewhat less than those in the tibialis anterior. Mean maximal MUFRs in the hamstrings are influenced by changes in knee joint angle, with lower firing rates in the biceps femoris compared with the semimembranosus-semitendinosus muscle group. We studied motor unit firing rates (MUFRs) at various voluntary contraction intensities in the hamstrings, one of the only major lower limb muscles to have MUFRs affected by muscle length changes. Within the hamstrings muscle-specific differences have greater impact on MUFRs than length changes, with the biceps femoris

  8. Na+,K+-pump stimulation improves contractility in isolated muscles of mice with hyperkalemic periodic paralysis.

    Science.gov (United States)

    Clausen, Torben; Nielsen, Ole Bækgaard; Clausen, Johannes D; Pedersen, Thomas Holm; Hayward, Lawrence J

    2011-07-01

    In patients with hyperkalemic periodic paralysis (HyperKPP), attacks of muscle weakness or paralysis are triggered by K(+) ingestion or rest after exercise. Force can be restored by muscle work or treatment with β(2)-adrenoceptor agonists. A missense substitution corresponding to a mutation in the skeletal muscle voltage-gated Na(+) channel (Na(v)1.4, Met1592Val) causing human HyperKPP was targeted into the mouse SCN4A gene (mutants). In soleus muscles prepared from these mutant mice, twitch, tetanic force, and endurance were markedly reduced compared with soleus from wild type (WT), reflecting impaired excitability. In mutant soleus, contractility was considerably more sensitive than WT soleus to inhibition by elevated [K(+)](o). In resting mutant soleus, tetrodotoxin (TTX)-suppressible (22)Na uptake and [Na(+)](i) were increased by 470 and 58%, respectively, and membrane potential was depolarized (by 16 mV, P Na(+),K(+) pump-mediated (86)Rb uptake was 83% larger than in WT. Salbutamol stimulated (86)Rb uptake and reduced [Na(+)](i) both in mutant and WT soleus. Stimulating Na(+),K(+) pumps with salbutamol restored force in mutant soleus and extensor digitorum longus (EDL). Increasing [Na(+)](i) with monensin also restored force in soleus. In soleus, EDL, and tibialis anterior muscles of mutant mice, the content of Na(+),K(+) pumps was 28, 62, and 33% higher than in WT, respectively, possibly reflecting the stimulating effect of elevated [Na(+)](i) on the synthesis of Na(+),K(+) pumps. The results confirm that the functional disorders of skeletal muscles in HyperKPP are secondary to increased Na(+) influx and show that contractility can be restored by acute stimulation of the Na(+),K(+) pumps. Calcitonin gene-related peptide (CGRP) restored force in mutant soleus but caused no detectable increase in (86)Rb uptake. Repeated excitation and capsaicin also restored contractility, possibly because of the release of endogenous CGRP from nerve endings in the isolated

  9. Spontaneous Metacognition in Rhesus Monkeys.

    Science.gov (United States)

    Rosati, Alexandra G; Santos, Laurie R

    2016-09-01

    Metacognition is the ability to think about thinking. Although monitoring and controlling one's knowledge is a key feature of human cognition, its evolutionary origins are debated. In the current study, we examined whether rhesus monkeys (Macaca mulatta; N = 120) could make metacognitive inferences in a one-shot decision. Each monkey experienced one of four conditions, observing a human appearing to hide a food reward in an apparatus consisting of either one or two tubes. The monkeys tended to search the correct location when they observed this baiting event, but engaged in information seeking-by peering into a center location where they could check both potential hiding spots-if their view had been occluded and information seeking was possible. The monkeys only occasionally approached the center when information seeking was not possible. These results show that monkeys spontaneously use information about their own knowledge states to solve naturalistic foraging problems, and thus provide the first evidence that nonhumans exhibit information-seeking responses in situations with which they have no prior experience. © The Author(s) 2016.

  10. Spontaneous flocking in human groups.

    Science.gov (United States)

    Belz, Michael; Pyritz, Lennart W; Boos, Margarete

    2013-01-01

    Flocking behaviour, as a type of self-organised collective behaviour, is described as the spatial formation of groups without global control and explicit inter-individual recruitment signals. It can be observed in many animals, such as bird flocks, shoals or herds of ungulates. Spatial attraction between humans as the central component of flocking behaviour has been simulated in a number of seminal models but it has not been detected experimentally in human groups so far. The two other sub-processes of this self-organised collective movement - collision avoidance and alignment - are excluded or held constant respectively in this study. We created a computer-based, multi-agent game where human players, represented as black dots, moved on a virtual playground. The participants were deprived of social cues about each other and could neither communicate verbally nor nonverbally. They played two games: (1) Single Game, where other players were invisible, and (2) Joint Game, where each player could see players' positions in a local radius around himself/herself. We found that individuals approached their neighbours spontaneously if their positions were visible, leading to less spatial dispersion of the whole group compared to moving alone. We conclude that human groups show the basic component of flocking behaviour without being explicitly instructed or rewarded to do so. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Simultaneous bilateral primary spontaneous pneumothorax

    Directory of Open Access Journals (Sweden)

    Arife Zeybek

    2014-04-01

    Full Text Available Simultaneous bilateral primary pneumothorax is a very rare (1.6 / 100,000 and life-threatening condition. Clinical presentation may vary from mild dyspnea to tension pneumothorax. It may be milder particularly in younger patients, but more severe in patients with advanced age, and tube thoracostomy is a life preserver in the latter group. Since mortality and recurrence rates following tube thoracostomy are high, endoscopic approaches to bilateral hemithorax have been reported in literature. Apical wedge resection and pleural procedures are recommended in video thoracoscopy or mini thoracotomy even if no bulla and/or bleb are detected. Bilateral surgical interventions and additional pleural procedures are associated with increased rate of post-operative complications and longer postoperative hospital-stays. As a first-line approach, the surgical method toward any side of lung with air leakage following a previous tube thoracostomy is considered less invasive, especially in younger patients. Here, we present a case of simultaneous bilateral primary spontaneous pneumothorax (SBPSP in a 21-year old male with no history of smoking and chronic pulmonary disease. A unilateral surgical intervention was performed, and no recurrence was observed during 5-year follow up.

  12. Bilateral spontaneous hemotympanum: Case report

    Directory of Open Access Journals (Sweden)

    Economou Nicolas C

    2006-10-01

    Full Text Available Abstract Background The most common causes of hemotympanum are therapeutic nasal packing, epistaxis, blood disorders and blunt trauma to the head. Hemotympanum is characterized as idiopathic, when it is detected in the presence of chronic otitis media. A rare case of spontaneous bilateral hemotympanum in a patient treated with anticoagulants is presented herein. Case presentation A 72-year-old male presented with acute deterioration of hearing. In the patient's medical history aortic valve replacement 1 year before presentation was reported. Since then he had been administered regularly coumarinic anticoagulants, with INR levels maintained between 3.4 and 4.0. Otoscopy revealed the presence of bilateral hemotympanum. The audiogram showed symmetrical moderately severe mixed hearing loss bilaterally, with the conductive component predominating. Tympanograms were flat bilaterally with absent acoustic reflexes. A computerized tomography scan showed the presence of fluid in the mastoid and middle ear bilaterally. Treatment was conservative and consisted of a 10-day course of antibiotics, anticongestants and temporary interruption of the anticoagulant therapy. After 3 weeks, normal tympanic membranes were found and hearing had returned to previous levels. Conclusion Anticoagulant intake should be included in the differential diagnosis of hemotympanum, because its detection and appropriate treatment may lead to resolution of the disorder.

  13. Continuum mechanical model for cross-linked actin networks with contractile bundles

    Science.gov (United States)

    Ferreira, J. P. S.; Parente, M. P. L.; Natal Jorge, R. M.

    2018-01-01

    In the context of a mechanical approach to cell biology, there is a close relationship between cellular function and mechanical properties. In recent years, an increasing amount of attention has been given to the coupling between biochemical and mechanical signals by means of constitutive models. In particular, on the active contractility of the actin cytoskeleton. Given the importance of the actin contraction on the physiological functions, this study propose a constitutive model to describe how the filamentous network controls its mechanics actively. Embedded in a soft isotropic ground substance, the network behaves as a viscous mechanical continuum, comprised of isotropically distributed cross-linked actin filaments and actomyosin bundles. Trough virtual rheometry experiments, the present model relates the dynamics of the myosin motors with the network stiffness, which is to a large extent governed by the time-scale of the applied deformations/forces.

  14. Contractile properties of rat fast-twitch skeletal muscle during reinnervation - Effects of testosterone and castration

    Science.gov (United States)

    Yeagle, S. P.; Mayer, R. F.; Max, S. R.

    1983-01-01

    The peroneal nerve of subject rats were crushed 1 cm from the muscle in order to examine the isometric contractile properties of skeletal muscle in the recovery sequency during reinnervation of normal, castrated, and testosterone-treated rats. The particular muscle studied was the extensor digitorum longus, with functional reinnervation first observed 8-9 days after nerve crush. No evidence was found that either castration or testosterone injections altered the process of reinnervation after the nerve crush, with the conclusion being valid at the 0.05 p level. The most reliable index of reinnervation was found to be the twitch:tetanus ratio, a factor of use in future studies of the reinnervation of skeletal muscle.

  15. Image Processing Techniques for Assessing Contractility in Isolated Adult Cardiac Myocytes

    Directory of Open Access Journals (Sweden)

    Carlos Bazan

    2009-01-01

    The physiologic application of the methodology is evaluated by assessing overall contraction in enzymatically dissociated adult rat cardiocytes. Our results demonstrate the effectiveness of the proposed approach in characterizing the true, two-dimensional, “shortening” in the contraction process of adult cardiocytes. We compare the performance of the proposed method to that of a popular edge detection system in the literature. The proposed method not only provides a more comprehensive assessment of the myocyte contraction process but also can potentially eliminate historical concerns and sources of errors caused by myocyte rotation or translation during contraction. Furthermore, the versatility of the image processing techniques makes the method suitable for determining myocyte shortening in cells that usually bend or move during contraction. The proposed method can be utilized to evaluate changes in contractile behavior resulting from drug intervention, disease modeling, transgeneity, or other common applications to mammalian cardiocytes.

  16. Prolonged ischemic heart disease and coronary artery bypass - relation to contractile reserve

    DEFF Research Database (Denmark)

    Kofoed, Klaus F; Bangsgaard, Regitze; Carstensen, Steen

    2002-01-01

    OBJECTIVE: A major effect of coronary artery bypass grafting (CABG) in patients with ischemic heart disease and impaired left ventricular (LV) contractile function is believed to be an improvement in LV function due to recovery of dysfunctional, but viable myocardium. However, recent studies have...... was correlated to the LV extent of myocardial metabolism--blood flow reverse mismatch. Most of the patients experienced an improvement in their angina pectoris, heart failure symptoms and exercise capacity after CABG; the overall 3-year survival was 77%. CONCLUSIONS: Patients with chronic ischemic heart disease...... indicated a time limit for such a recovery. We therefore investigated the extent of viable myocardium in patients with impaired LV function due to ischemic heart disease after a prolonged strategy of medical treatment and its relation to changes in clinical variables after CABG. METHODS: Forty...

  17. Clock frequency estimation under spontaneous emission

    Science.gov (United States)

    Qin, Xi-Zhou; Huang, Jia-Hao; Zhong, Hong-Hua; Lee, Chaohong

    2018-02-01

    We investigate the quantum dynamics of a driven two-level system under spontaneous emission and its application in clock frequency estimation. By using the Lindblad equation to describe the system, we analytically obtain its exact solutions, which show three different regimes: Rabi oscillation, damped oscillation, and overdamped decay. From the analytical solutions, we explore how the spontaneous emission affects the clock frequency estimation. We find that under a moderate spontaneous emission rate, the transition frequency can still be inferred from the Rabi oscillation. Our results enable potential practical applications in frequency measurement and quantum control under decoherence.

  18. Spontaneous Bacterial Peritonitis in Subclinical Hypothyroidism

    Directory of Open Access Journals (Sweden)

    Dalip Gupta

    2013-11-01

    Full Text Available Hypothyroidism is an uncommon cause of ascites. Here we describe a case of a 75 year-old female patient with spontaneous bacterial peritonitis and subclinical hypothyroidism that resolved with thyroid replacement and antibiotic therapy respectively. Ascitic fluid analysis revealed a gram-positive bacterium on gram staining. A review of the literature revealed just one other reported case of myxoedema ascites with concomitant spontaneous bacterial peritonitis and no case has till been reported of spontaneous bacterial peritonitis in subclinical hypothyroidism.

  19. Spontaneous regression of an invasive thymoma.

    Science.gov (United States)

    Yutaka, Yojiro; Omasa, Mitsugu; Shikuma, Kei; Okuda, Masato; Taki, Toshihiko

    2009-05-01

    Although there are many reports of spontaneous regression of noninvasive thymoma, there are no reports of spontaneous regression of an invasive thymoma. Moreover, the mechanism of the spontaneous regression is still unknown. The present case concerns a 47-year-old man who presented with chest pain. Computed tomography (CT) showed a large anterior mediastinal mass with left pleural effusion that occluded the innominate vein. The tissue obtained by video-assisted thoracic surgery suggested a diagnosis of invasive thymic carcinoma. One month later CT showed prominent regression of the tumor, and the tumor was completely resected. On pathology, the diagnosis was thymoma type B3.

  20. Spontaneous Dissection of the Superior Mesenteric Artery

    International Nuclear Information System (INIS)

    Sheldon, Patrick J.; Esther, James B.; Sheldon, Elana L.; Sparks, Steven R.; Brophy, David P.; Oglevie, Steven B.

    2001-01-01

    Spontaneous dissection of the superior mesenteric artery (SMA) is a rare occurrence, especially when not associated with aortic dissection. Currently, only 28 cases appear to have been reported. Due to the scarcity of cases in the literature, the natural history of isolated, spontaneous SMA dissection is unclear. CT has been reported to be useful for the initial diagnosis of SMA dissection [2-5]. We present two recent cases of spontaneous SMA dissection in which enhanced spiral CT was instrumental in following the disease process and guiding clinical decision making

  1. Abnormal glucose metabolism is associated with reduced left ventricular contractile reserve and exercise intolerance in patients with chronic heart failure

    DEFF Research Database (Denmark)

    Egstrup, M; Kistorp, C N; Schou, M

    2013-01-01

    intolerance related to diabetes. CONCLUSION: Diabetes, known or newly detected by OGTT, is independently associated with reduced LV contractile reserve and exercise...... intolerance in outpatients with systolic HF. These findings may offer one explanation for the excess mortality related to diabetes in HF....

  2. TRPM4 Is a Novel Component of the Adhesome Required for Focal Adhesion Disassembly, Migration and Contractility.

    Directory of Open Access Journals (Sweden)

    Mónica Cáceres

    Full Text Available Cellular migration and contractility are fundamental processes that are regulated by a variety of concerted mechanisms such as cytoskeleton rearrangements, focal adhesion turnover, and Ca2+ oscillations. TRPM4 is a Ca2+-activated non-selective cationic channel (Ca2+-NSCC that conducts monovalent but not divalent cations. Here, we used a mass spectrometry-based proteomics approach to identify putative TRPM4-associated proteins. Interestingly, the largest group of these proteins has actin cytoskeleton-related functions, and among these nine are specifically annotated as focal adhesion-related proteins. Consistent with these results, we found that TRPM4 localizes to focal adhesions in cells from different cellular lineages. We show that suppression of TRPM4 in MEFs impacts turnover of focal adhesions, serum-induced Ca2+ influx, focal adhesion kinase (FAK and Rac activities, and results in reduced cellular spreading, migration and contractile behavior. Finally, we demonstrate that the inhibition of TRPM4 activity alters cellular contractility in vivo, affecting cutaneous wound healing. Together, these findings provide the first evidence, to our knowledge, for a TRP channel specifically localized to focal adhesions, where it performs a central role in modulating cellular migration and contractility.

  3. TRPM4 Is a Novel Component of the Adhesome Required for Focal Adhesion Disassembly, Migration and Contractility

    Science.gov (United States)

    Cáceres, Mónica; Ortiz, Liliana; Recabarren, Tatiana; Romero, Anibal; Colombo, Alicia; Leiva-Salcedo, Elías; Varela, Diego; Rivas, José; Silva, Ian; Morales, Diego; Campusano, Camilo; Almarza, Oscar; Simon, Felipe; Toledo, Hector; Park, Kang-Sik; Trimmer, James S.; Cerda, Oscar

    2015-01-01

    Cellular migration and contractility are fundamental processes that are regulated by a variety of concerted mechanisms such as cytoskeleton rearrangements, focal adhesion turnover, and Ca2+ oscillations. TRPM4 is a Ca2+-activated non-selective cationic channel (Ca2+-NSCC) that conducts monovalent but not divalent cations. Here, we used a mass spectrometry-based proteomics approach to identify putative TRPM4-associated proteins. Interestingly, the largest group of these proteins has actin cytoskeleton-related functions, and among these nine are specifically annotated as focal adhesion-related proteins. Consistent with these results, we found that TRPM4 localizes to focal adhesions in cells from different cellular lineages. We show that suppression of TRPM4 in MEFs impacts turnover of focal adhesions, serum-induced Ca2+ influx, focal adhesion kinase (FAK) and Rac activities, and results in reduced cellular spreading, migration and contractile behavior. Finally, we demonstrate that the inhibition of TRPM4 activity alters cellular contractility in vivo, affecting cutaneous wound healing. Together, these findings provide the first evidence, to our knowledge, for a TRP channel specifically localized to focal adhesions, where it performs a central role in modulating cellular migration and contractility. PMID:26110647

  4. Effect of Propafenone on the Contractile Activity of Latissimus Dorsi Muscle Isolated in an Organ Chamber: Experimental Study in Rats

    Directory of Open Access Journals (Sweden)

    Ricardo Simões

    2002-03-01

    Full Text Available OBJECTIVE: To study the effect of propafenone on the contractile function of latissimus dorsi muscle isolated from rats in an organ chamber. METHODS: We studied 20 latissimus dorsi muscles of Wistar rats and divided them into 2 groups: group I (n=10, or control group - we studied the feasibility of muscle contractility; group II (n=10, in which the contralateral muscles were grouped - we analyzed the effect of propafenone on muscle contractility. After building a muscle ring, 8 periods of sequential 2-minute baths were performed, with intervals of preprogrammed electrical stimulation using a pacemaker of 50 stimuli/min. In group II, propafenone, at the concentration of 9.8 µg/mL, was added to the bath in period 2 and withdrawn in period 4. RESULTS: In group I, no significant depression in muscle contraction occurred up to period 5 (p>0.05. In group II, a significant depression occurred in all periods, except between the last 2 periods (p0.05. CONCLUSION: Propafenone had a depressing effect on the contractile function of latissimus dorsi muscle isolated from rats and studied in an organ chamber.

  5. Growth differentiation factor 15 impairs aortic contractile and relaxing function through altered caveolar signaling of the endothelium

    NARCIS (Netherlands)

    Mazagova, Magdalena; Buikema, Hendrik; Landheer, Sjoerd W.; Vavrinec, Peter; van Buiten, Azuwerus; Henning, Robert H.; Deelman, Leo E.

    Mazagova M, Buikema H, Landheer SW, Vavrinec P, van Buiten A, Henning RH, Deelman LE. Growth differentiation factor 15 impairs aortic contractile and relaxing function through altered caveolar signaling of the endothelium. Am J Physiol Heart Circ Physiol 304: H709-H718, 2013. First published

  6. Contractile responses to natural tachykinins and selective tachykinin analogs in normal and inflamed ileal and colonic muscle.

    Science.gov (United States)

    Al-Saffar, A; Hellström, P M

    2001-05-01

    Tachykinins and acetylcholine are main physiological motility stimulators in the gut by their effects exerted through neurokinin and muscarinic receptors. Longitudinal and circular muscle strips from normal ileum and colon or corresponding tissues from patients with inflammatory bowel disease were studied in organ baths. Contractile responses to the tachykinins substance P, neurokinin A, neurokinin B and neuropeptide gamma and specific analogs for their respective receptors were compared to acetylcholine. Acetylcholine caused concentration-dependent phasic contractions in longitudinal and circular muscle of normal ileum and colon (both P tachykinins and their specific analogs caused concentration-dependent phasic, tonic and rhythmic contractions (each P tachykinin analogs, Nle10-NKA(4-10) was more potent than substance P methyl ester and senktide, indicating neurokinin 2 receptors are predominant for contractile effects of tachykinins. In inflamed tissues, contractile responses to tachykinins were reduced to 0%-42% in ileum (P tachykinins exert gut contractile effects, of similar strength as acetylcholine, predominantly through activation of neurokinin 2 receptors. These responses are greatly reduced in inflamed tissues of ulcerative colitis and Crohn disease.

  7. Gated dynamic 31P MRS shows reduced contractile phosphocreatine breakdown in mice deficient in cytosolic creatine kinase and adenylate kinase.

    NARCIS (Netherlands)

    Kan, H.E.; Veltien, A.A.; Arnts, H.F.G.; Nabuurs, C.I.H.C.; Luijten, B.M.A.; Haan, A. de; Wieringa, B.; Heerschap, A.

    2009-01-01

    We developed a new dedicated measurement protocol for dynamic (31)P MRS analysis in contracting calf muscles of the mouse, using minimally invasive assessment of the contractile force combined with the acquisition of spectroscopic data gated to muscle contraction and determination of phosphocreatine

  8. Effect of a Periodized Power Training Program on the Functional Performances and Contractile Properties of the Quadriceps in Sprinters

    Science.gov (United States)

    Kamandulis, Sigitas; Skurvydas, Albertas; Brazaitis, Marius; Stanislovaitis, Aleksas; Duchateau, Jacques; Stanislovaitiene, Jurate

    2012-01-01

    Our purpose was to compare the effect of a periodized preparation consisting of power endurance training and high-intensity power training on the contractile properties of the quadriceps muscle and functional performances in well trained male sprinters (n = 7). After 4 weeks of high-intensity power training, 60-m sprint running time improved by an…

  9. Effects of testosterone on contractile properties of sexually dimorphic forelimb muscles in male bullfrogs (Rana catesbeiana, Shaw 1802).

    Science.gov (United States)

    Kampe, Aaron R; Peters, Susan E

    2013-01-01

    This study examined the effects of testosterone (T) on the contractile properties of two sexually dimorphic forelimb muscles and one non-dimorphic muscle in male bullfrogs (Rana catesbeiana, Shaw 1802). The dimorphic muscles in castrated males with testosterone replacement (T+) achieved higher forces and lower fatigability than did castrated males without replaced testosterone (T0 males), but the magnitude of the differences was low and many of the pair-wise comparisons of each muscle property were not statistically significant. However, when taken as a whole, the means of seven contractile properties varied in the directions expected of masculine values in T+ animals in the sexually dimorphic muscles. Moreover, these data, compared with previous data on male and female bullfrogs, show that values for T+ males are similar to normal males and are significantly different from females. The T0 males tended to be intermediate in character between T+ males and females, generally retaining masculine values. This suggests that the exposure of young males to T in their first breeding season produces a masculinizing effect on the sexually dimorphic muscles that is not reversed between breeding seasons when T levels are low. The relatively minor differences in contractile properties between T+ and T0 males may indicate that as circulating T levels rise during breeding season in normal males, contractile properties can be enhanced rapidly to maximal functional levels for breeding success.

  10. Effects of testosterone on contractile properties of sexually dimorphic forelimb muscles in male bullfrogs (Rana catesbeiana, Shaw 1802

    Directory of Open Access Journals (Sweden)

    Aaron R. Kampe

    2013-07-01

    This study examined the effects of testosterone (T on the contractile properties of two sexually dimorphic forelimb muscles and one non-dimorphic muscle in male bullfrogs (Rana catesbeiana, Shaw 1802. The dimorphic muscles in castrated males with testosterone replacement (T+ achieved higher forces and lower fatigability than did castrated males without replaced testosterone (T0 males, but the magnitude of the differences was low and many of the pair-wise comparisons of each muscle property were not statistically significant. However, when taken as a whole, the means of seven contractile properties varied in the directions expected of masculine values in T+ animals in the sexually dimorphic muscles. Moreover, these data, compared with previous data on male and female bullfrogs, show that values for T+ males are similar to normal males and are significantly different from females. The T0 males tended to be intermediate in character between T+ males and females, generally retaining masculine values. This suggests that the exposure of young males to T in their first breeding season produces a masculinizing effect on the sexually dimorphic muscles that is not reversed between breeding seasons when T levels are low. The relatively minor differences in contractile properties between T+ and T0 males may indicate that as circulating T levels rise during breeding season in normal males, contractile properties can be enhanced rapidly to maximal functional levels for breeding success.

  11. Alterations in serotonin receptor-induced contractility of bovine lateral saphenous vein in cattle grazing endophyte-infected tall fescue

    Science.gov (United States)

    As part of a large 2-year study documenting the physiologic impact of grazing endophyte-infected tall fescue on growing cattle, 2 experiments were conducted to characterize and evaluate the effects of grazing 2 levels of toxic endophyte-infected tall fescue pastures on vascular contractility and ser...

  12. Effect of acute and chronic simvastatin treatment on post-ischemic contractile dysfunction in isolated rat heart

    Czech Academy of Sciences Publication Activity Database

    Szárszoi, Ondrej; Malý, J.; Ošťádal, P.; Netuka, I.; Bešík, J.; Kolář, František; Ošťádal, Bohuslav

    2008-01-01

    Roč. 57, č. 5 (2008), s. 793-796 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510 Institutional research plan: CEZ:AV0Z50110509 Keywords : simvastatin * contractile dysfunction * protection Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.653, year: 2008

  13. The Effect of Cleft Palate Repair on Contractile Properties of Single Permeabilized Muscle Fibers From Congenitally Cleft Goats Palates

    Science.gov (United States)

    A cleft palate goat model was used to study the contractile properties of the levator veli palatini (LVP) muscle which is responsible for the movement of the soft palate. In 15-25% of patients that undergo palatoplasty, residual velopharyngeal insufficiency (VPI) remains a problem and often require...

  14. AMP-activated protein kinase deficiency rescues paraquat-induced cardiac contractile dysfunction through an autophagy-dependent mechanism.

    Science.gov (United States)

    Wang, Qiurong; Yang, Lifang; Hua, Yinan; Nair, Sreejayan; Xu, Xihui; Ren, Jun

    2014-11-01

    Paraquat, a quaternary nitrogen herbicide, is a highly toxic prooxidant resulting in multi-organ failure including the heart although the underlying mechanism still remains elusive. This study was designed to examine the role of the cellular fuel sensor AMP-activated protein kinase (AMPK) in paraquat-induced cardiac contractile and mitochondrial injury. Wild-type and transgenic mice with overexpression of a mutant AMPK α2 subunit (kinase dead, KD), with reduced activity in both α1 and α2 subunits, were administered with paraquat (45 mg/kg) for 48 h. Paraquat elicited cardiac mechanical anomalies including compromised echocardiographic parameters (elevated left ventricular end-systolic diameter and reduced factional shortening), suppressed cardiomyocyte contractile function, intracellular Ca(2+) handling, reduced cell survival, and overt mitochondrial damage (loss in mitochondrial membrane potential). In addition, paraquat treatment promoted phosphorylation of AMPK and autophagy. Interestingly, deficiency in AMPK attenuated paraquat-induced cardiac contractile and intracellular Ca(2+) derangement. The beneficial effect of AMPK inhibition was associated with inhibition of the AMPK-TSC-mTOR-ULK1 signaling cascade. In vitro study revealed that inhibitors for AMPK and autophagy attenuated paraquat-induced cardiomyocyte contractile dysfunction. Taken together, our findings revealed that AMPK may mediate paraquat-induced myocardial anomalies possibly by regulating the AMPK/mTOR-dependent autophagy. © The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  15. Does Spontaneous Favorability to Power (vs. Universalism) Values Predict Spontaneous Prejudice and Discrimination?

    Science.gov (United States)

    Souchon, Nicolas; Maio, Gregory R; Hanel, Paul H P; Bardin, Brigitte

    2017-10-01

    We conducted five studies testing whether an implicit measure of favorability toward power over universalism values predicts spontaneous prejudice and discrimination. Studies 1 (N = 192) and 2 (N = 86) examined correlations between spontaneous favorability toward power (vs. universalism) values, achievement (vs. benevolence) values, and a spontaneous measure of prejudice toward ethnic minorities. Study 3 (N = 159) tested whether conditioning participants to associate power values with positive adjectives and universalism values with negative adjectives (or inversely) affects spontaneous prejudice. Study 4 (N = 95) tested whether decision bias toward female handball players could be predicted by spontaneous attitude toward power (vs. universalism) values. Study 5 (N = 123) examined correlations between spontaneous attitude toward power (vs. universalism) values, spontaneous importance toward power (vs. universalism) values, and spontaneous prejudice toward Black African people. Spontaneous positivity toward power (vs. universalism) values was associated with spontaneous negativity toward minorities and predicted gender bias in a decision task, whereas the explicit measures did not. These results indicate that the implicit assessment of evaluative responses attached to human values helps to model value-attitude-behavior relations. © 2016 The Authors. Journal of Personality Published by Wiley Periodicals, Inc.

  16. Cardioselective Dominant-negative Thyroid Hormone Receptor (Δ337T) Modulates Myocardial Metabolism and Contractile Dfficiency

    Energy Technology Data Exchange (ETDEWEB)

    Hyyti, Outi M.; Olson, Aaron; Ge, Ming; Ning, Xue-Han; Buroker, Norman E.; Chung, Youngran; Jue, Thomas; Portman, Michael A.

    2008-06-03

    Dominant- negative thyroid hormone receptors (TRs) show elevated expression relative to ligand-binding TRs during cardiac hypertrophy. We tested the hypothesis that overexpression of a dominant-negative TR alters cardiac metabolism and contractile efficiency (CE). We used mice expressing the cardioselective dominant-negative TRβ1 mutation Δ337T. Isolated working Δ337T hearts and nontransgenic control (Con) hearts were perfused with 13C-labeled free fatty acids (FFA), acetoacetate (ACAC), lactate, and glucose at physiological concentrations for 30 min. 13C NMR spectroscopy and isotopomer analyses were used to determine substrate flux and fractional contributions (Fc) of acetyl-CoA to the citric acid cycle (CAC). Δ337T hearts exhibited rate depression but higher developed pressure and CE, defined as work per oxygen consumption (MV˙ O2). Unlabeled substrate Fc from endogenous sources was higher in Δ337T, but ACAC Fc was lower. Fluxes through CAC, lactate, ACAC, and FFA were reduced in Δ337T. CE and Fc differences were reversed by pacing Δ337T to Con rates, accompanied by an increase in FFA Fc. Δ337T hearts lacked the ability to increase MV˙ O2. Decreases in protein expression for glucose transporter-4 and hexokinase-2 and increases in pyruvate dehydrogenase kinase-2 and -4 suggest that these hearts are unable to increase carbohydrate oxidation in response to stress. These data show that Δ337T alters the metabolic phenotype in murine heart by reducing substrate flux for multiple pathways. Some of these changes are heart rate dependent, indicating that the substrate shift may represent an accommodation to altered contractile protein kinetics, which can be disrupted by pacing stress.

  17. Modeling beta-adrenergic control of cardiac myocyte contractility in silico

    Science.gov (United States)

    Saucerman, Jeffrey J.; Brunton, Laurence L.; Michailova, Anushka P.; McCulloch, Andrew D.; McCullough, A. D. (Principal Investigator)

    2003-01-01

    The beta-adrenergic signaling pathway regulates cardiac myocyte contractility through a combination of feedforward and feedback mechanisms. We used systems analysis to investigate how the components and topology of this signaling network permit neurohormonal control of excitation-contraction coupling in the rat ventricular myocyte. A kinetic model integrating beta-adrenergic signaling with excitation-contraction coupling was formulated, and each subsystem was validated with independent biochemical and physiological measurements. Model analysis was used to investigate quantitatively the effects of specific molecular perturbations. 3-Fold overexpression of adenylyl cyclase in the model allowed an 85% higher rate of cyclic AMP synthesis than an equivalent overexpression of beta 1-adrenergic receptor, and manipulating the affinity of Gs alpha for adenylyl cyclase was a more potent regulator of cyclic AMP production. The model predicted that less than 40% of adenylyl cyclase molecules may be stimulated under maximal receptor activation, and an experimental protocol is suggested for validating this prediction. The model also predicted that the endogenous heat-stable protein kinase inhibitor may enhance basal cyclic AMP buffering by 68% and increasing the apparent Hill coefficient of protein kinase A activation from 1.0 to 2.0. Finally, phosphorylation of the L-type calcium channel and phospholamban were found sufficient to predict the dominant changes in myocyte contractility, including a 2.6x increase in systolic calcium (inotropy) and a 28% decrease in calcium half-relaxation time (lusitropy). By performing systems analysis, the consequences of molecular perturbations in the beta-adrenergic signaling network may be understood within the context of integrative cellular physiology.

  18. Exposure to low mercury concentration in vivo impairs myocardial contractile function

    International Nuclear Information System (INIS)

    Furieri, Lorena Barros; Fioresi, Mirian; Junior, Rogerio Faustino Ribeiro; Bartolome, Maria Visitacion; Fernandes, Aurelia Araujo; Cachofeiro, Victoria; Lahera, Vicente; Salaices, Mercedes; Stefanon, Ivanita; Vassallo, Dalton Valentim

    2011-01-01

    Increased cardiovascular risk after mercury exposure has been described but cardiac effects resulting from controlled chronic treatment are not yet well explored. We analyzed the effects of chronic exposure to low mercury concentrations on hemodynamic and ventricular function of isolated hearts. Wistar rats were treated with HgCl 2 (1st dose 4.6 μg/kg, subsequent dose 0.07 μg/kg/day, im, 30 days) or vehicle. Mercury treatment did not affect blood pressure (BP) nor produced cardiac hypertrophy or changes of myocyte morphometry and collagen content. This treatment: 1) in vivo increased left ventricle end diastolic pressure (LVEDP) without changing left ventricular systolic pressure (LVSP) and heart rate; 2) in isolated hearts reduced LV isovolumic systolic pressure and time derivatives, and β-adrenergic response; 3) increased myosin ATPase activity; 4) reduced Na + -K + ATPase (NKA) activity; 5) reduced protein expression of SERCA and phosphorylated phospholamban on serine 16 while phospholamban expression increased; as a consequence SERCA/phospholamban ratio reduced; 6) reduced sodium/calcium exchanger (NCX) protein expression and α-1 isoform of NKA, whereas α-2 isoform of NKA did not change. Chronic exposure for 30 days to low concentrations of mercury does not change BP, heart rate or LVSP but produces small but significant increase of LVEDP. However, in isolated hearts mercury treatment promoted contractility dysfunction as a result of the decreased NKA activity, reduction of NCX and SERCA and increased PLB protein expression. These findings offer further evidence that mercury chronic exposure, even at small concentrations, is an environmental risk factor affecting heart function. - Highlights: → Unchanges blood pressure, heart rate, systolic pressure. → Increases end diastolic pressure. → Promotes cardiac contractility dysfunction. → Decreases NKA activity, NCX and SERCA, increases PLB protein expression. → Small concentrations constitutes

  19. Pentamidine rescues contractility and rhythmicity in a Drosophila model of myotonic dystrophy heart dysfunction

    Directory of Open Access Journals (Sweden)

    Mouli Chakraborty

    2015-12-01

    Full Text Available Up to 80% of individuals with myotonic dystrophy type 1 (DM1 will develop cardiac abnormalities at some point during the progression of their disease, the most common of which is heart blockage of varying degrees. Such blockage is characterized by conduction defects and supraventricular and ventricular tachycardia, and carries a high risk of sudden cardiac death. Despite its importance, very few animal model studies have focused on the heart dysfunction in DM1. Here, we describe the characterization of the heart phenotype in a Drosophila model expressing pure expanded CUG repeats under the control of the cardiomyocyte-specific driver GMH5-Gal4. Morphologically, expression of 250 CUG repeats caused abnormalities in the parallel alignment of the spiral myofibrils in dissected fly hearts, as revealed by phalloidin staining. Moreover, combined immunofluorescence and in situ hybridization of Muscleblind and CUG repeats, respectively, confirmed detectable ribonuclear foci and Muscleblind sequestration, characteristic features of DM1, exclusively in flies expressing the expanded CTG repeats. Similarly to what has been reported in humans with DM1, heart-specific expression of toxic RNA resulted in reduced survival, increased arrhythmia, altered diastolic and systolic function, reduced heart tube diameters and reduced contractility in the model flies. As a proof of concept that the fly heart model can be used for in vivo testing of promising therapeutic compounds, we fed flies with pentamidine, a compound previously described to improve DM1 phenotypes. Pentamidine not only released Muscleblind from the CUG RNA repeats and reduced ribonuclear formation in the Drosophila heart, but also rescued heart arrhythmicity and contractility, and improved fly survival in animals expressing 250 CUG repeats.

  20. Effect of beta-alanine and carnosine supplementation on muscle contractility in mice.

    Science.gov (United States)

    Everaert, Inge; Stegen, Sanne; Vanheel, Bert; Taes, Youri; Derave, Wim

    2013-01-01

    Enhanced carnosine levels have been shown to be ergogenic for high-intensity exercise performances, although the role of carnosine in the control of muscle function is poorly understood. Therefore, the aim of this study was to investigate the effect of long-term supplementation with increasing doses of carnosine and beta-alanine on muscle carnosine, anserine, and taurine levels and on in vitro contractility and fatigue in mice. Male Naval Medical Research Institute mice (n = 66) were control fed or supplemented with either carnosine (0.1%, 0.5%, or 1.8%) or beta-alanine (0.6 or 1.2%) in their drinking water for 8-12 wk. Soleus and extensor digitorum longus (EDL) were tested for in vitro contractile properties, and carnosine, anserine, and taurine content were measured in EDL and tibialis anterior by high-performance liquid chromatography. Only supplementation with 1.8% carnosine and 1.2% beta-alanine resulted in markedly higher carnosine (up to +160%) and anserine levels (up to +46%) compared with control mice. Beta-alanine supplementation (1.2%) resulted in increased fatigue resistance in the beginning of the fatigue protocol in soleus (+2%-4%) and a marked leftward shift of the force-frequency relation in EDL (10%-31% higher relative forces). Comparable with humans, beta-alanine availability seems to be the rate-limiting step for synthesis of muscle histidine-containing dipeptides in mice. Moreover, muscle histidine-containing dipeptides loading in mice moderately and muscle dependently affects excitation-contraction coupling and fatigue.

  1. A short-term statin treatment changes the contractile properties of fast-twitch skeletal muscles.

    Science.gov (United States)

    Piette, Antoine Boulanger; Dufresne, Sébastien S; Frenette, Jérôme

    2016-10-28

    Cumulative evidence indicates that statins induce myotoxicity. However, the lack of understanding of how statins affect skeletal muscles at the structural, functional, and physiological levels hampers proper healthcare management. The purpose of the present study was to investigate the early after-effects of lovastatin on the slow-twitch soleus (Sol) and fast-twitch extensor digitorum longus (EDL) muscles. Adult C57BL/6 mice were orally administrated with placebo or lovastatin [50 mg/kg/d] for 28 days. At the end of the treatment, the isometric ex vivo contractile properties of the Sol and EDL muscles were measured. Subtetanic and tetanic contractions were assessed and contraction kinetics were recorded. The muscles were then frozen for immunohistochemical analyses. Data were analyzed by two-way ANOVA followed by an a posteriori Tukey's test. The short-term lovastatin treatment did not induce muscle mass loss, muscle fiber atrophy, or creatine kinase (CK) release. It had no functional impact on slow-twitch Sol muscles. However, subtetanic stimulations at 10 Hz provoked greater force production in fast-twitch EDL muscles. The treatment also decreased the maximal rate of force development (dP/dT) of twitch contractions and prolonged the half relaxation time (1/2RT) of tetanic contractions of EDL muscles. An early short-term statin treatment induced subtle but significant changes in some parameters of the contractile profile of EDL muscles, providing new insights into the selective initiation of statin-induced myopathy in fast-twitch muscles.

  2. Assessment of pelvic floor muscle contractility: digital palpation versus 2D and 3D perineal ultrasound.

    Science.gov (United States)

    Albrich, Stefan; Steetskamp, Joscha; Knoechel, Sophie-Luise; Porta, Saskia; Hoffmann, Gerald; Skala, Christine

    2016-04-01

    The aim of our study was to investigate 2D and 3D ultrasound assessment of pelvic floor muscle contractility as an objective non-invasive diagnostic tool in urogynecologic patients. Patients from our urogynecological outpatient clinic were examined clinically by a single investigator including digital palpation as well as 2D and 3D perineal ultrasound. Muscle contractility was graded according to the modified Oxford Score and ultrasound images were saved for later analysis. Stored images were evaluated offline by another investigator blinded to all clinical data at a later stage. Bladder neck distance from pubic symphysis and symphysis-levator distance were measured in 2D at rest and during maximal pelvic floor muscle contraction. Hiatal area at the level of minimal hiatal dimensions as a 3D ultrasound parameter was measured at rest and during maximal pelvic floor muscle contraction, too. Spearman's rho was used to calculate statistical correlation between ultrasound parameters and digital assessment. A total of 114 patients were examined in our study. We found a significant correlation between modified Oxford Score and 2D ultrasound parameters of elongation of bladder neck length (Spearman's rho 0.292, p = 0.002) and reduction of symphysis-levator distance (Spearman's rho 0.0.301, p = 0.001), respectively. In addition, we detected a statistical significant correlation of modified Oxford Score and reduction of hiatal area in 3D ultrasound (Spearman's rho 0.458, p pelvic floor muscle strength with 2D and 3D ultrasound parameters as an objective diagnostic tool.

  3. Leucine elicits myotube hypertrophy and enhances maximal contractile force in tissue engineered skeletal muscle in vitro.

    Science.gov (United States)

    Martin, Neil R W; Turner, Mark C; Farrington, Robert; Player, Darren J; Lewis, Mark P

    2017-10-01

    The amino acid leucine is thought to be important for skeletal muscle growth by virtue of its ability to acutely activate mTORC1 and enhance muscle protein synthesis, yet little data exist regarding its impact on skeletal muscle size and its ability to produce force. We utilized a tissue engineering approach in order to test whether supplementing culture medium with leucine could enhance mTORC1 signaling, myotube growth, and muscle function. Phosphorylation of the mTORC1 target proteins 4EBP-1 and rpS6 and myotube hypertrophy appeared to occur in a dose dependent manner, with 5 and 20 mM of leucine inducing similar effects, which were greater than those seen with 1 mM. Maximal contractile force was also elevated with leucine supplementation; however, although this did not appear to be enhanced with increasing leucine doses, this effect was completely ablated by co-incubation with the mTOR inhibitor rapamycin, showing that the augmented force production in the presence of leucine was mTOR sensitive. Finally, by using electrical stimulation to induce chronic (24 hr) contraction of engineered skeletal muscle constructs, we were able to show that the effects of leucine and muscle contraction are additive, since the two stimuli had cumulative effects on maximal contractile force production. These results extend our current knowledge of the efficacy of leucine as an anabolic nutritional aid showing for the first time that leucine supplementation may augment skeletal muscle functional capacity, and furthermore validates the use of engineered skeletal muscle for highly-controlled investigations into nutritional regulation of muscle physiology. © 2017 The Authors. Journal of Cellular Physiology Published by wiley periodicals, Inc.

  4. Moderate Continuous Aerobic Exercise Training Improves Cardiomyocyte Contractility in Β1 Adrenergic Receptor Knockout Mice

    Directory of Open Access Journals (Sweden)

    Aurora Corrêa Rodrigues

    2018-02-01

    Full Text Available Abstract Background: The lack of cardiac β1-adrenergic receptors (β1-AR negatively affects the regulation of both cardiac inotropy and lusitropy, leading, in the long term, to heart failure (HF. Moderate-intensity aerobic exercise (MCAE is recommended as an adjunctive therapy for patients with HF. Objective: We tested the effects of MCAE on the contractile properties of left ventricular (LV myocytes from β1 adrenergic receptor knockout (β1ARKO mice. Methods: Four- to five-month-old male wild type (WT and β1ARKO mice were divided into groups: WT control (WTc and trained (WTt; and β1ARKO control (β1ARKOc and trained (β1ARKOt. Animals from trained groups were submitted to a MCAE regimen (60 min/day; 60% of maximal speed, 5 days/week on a treadmill, for 8 weeks. P ≤ 0.05 was considered significant in all comparisons. Results: The β1ARKO and exercised mice exhibited a higher (p < 0.05 running capacity than WT and sedentary ones, respectively. The β1ARKO mice showed higher body (BW, heart (HW and left ventricle (LVW weights, as well as the HW/BW and LVW/BW than WT mice. However, the MCAE did not affect these parameters. Left ventricular myocytes from β1ARKO mice showed increased (p < 0.05 amplitude and velocities of contraction and relaxation than those from WT. In addition, MCAE increased (p < 0.05 amplitude and velocities of contraction and relaxation in β1ARKO mice. Conclusion: MCAE improves myocyte contractility in the left ventricle of β1ARKO mice. This is evidence to support the therapeutic value of this type of exercise training in the treatment of heart diseases involving β1-AR desensitization or reduction.

  5. Does phototherapy enhance skeletal muscle contractile function and postexercise recovery? A systematic review.

    Science.gov (United States)

    Borsa, Paul A; Larkin, Kelly A; True, Jerry M

    2013-01-01

    Recently, researchers have shown that phototherapy administered to skeletal muscle immediately before resistance exercise can enhance contractile function, prevent exercise-induced cell damage, and improve postexercise recovery of strength and function. To critically evaluate original research addressing the ability of phototherapeutic devices, such as lasers and light-emitting diodes (LEDs), to enhance skeletal muscle contractile function, reduce exercise-induced muscle fatigue, and facilitate postexercise recovery. We searched the electronic databases PubMed, SPORTDiscus, Web of Science, Scopus, and Rehabilitation & Physical Medicine without date limitations for the following key words: laser therapy, phototherapy, fatigue, exercise, circulation, microcirculation, and photobiomodulation. Eligible studies had to be original research published in English as full papers, involve human participants, and receive a minimum score of 7 out of 10 on the Physiotherapy Evidence Database (PEDro) scale. Data of interest included elapsed time to fatigue, total number of repetitions to fatigue, total work performed, maximal voluntary isometric contraction (strength), electromyographic activity, and postexercise biomarker levels. We recorded the PEDro scores, beam characteristics, and treatment variables and calculated the therapeutic outcomes and effect sizes for the data sets. In total, 12 randomized controlled trials met the inclusion criteria. However, we excluded data from 2 studies, leaving 32 data sets from 10 studies. Twenty-four of the 32 data sets contained differences between active phototherapy and sham (placebo-control) treatment conditions for the various outcome measures. Exposing skeletal muscle to single-diode and multidiode laser or multidiode LED therapy was shown to positively affect physical performance by delaying the onset of fatigue, reducing the fatigue response, improving postexercise recovery, and protecting cells from exercise-induced damage

  6. Spatio-temporal changes of lymphatic contractility and drainage patterns following lymphadenectomy in mice.

    Directory of Open Access Journals (Sweden)

    Sunkuk Kwon

    Full Text Available To investigate the redirection of lymphatic drainage post-lymphadenectomy using non-invasive near-infrared fluorescence (NIRF imaging, and to subsequently assess impact on metastasis.Cancer-acquired lymphedema arises from dysfunctional fluid transport after lymphadenectomy performed for staging and to disrupt drainage pathways for regional control of disease. However, little is known about the normal regenerative processes of the lymphatics in response to lymphadenectomy and how these responses can be accelerated, delayed, or can impact metastasis.Changes in lymphatic "pumping" function and drainage patterns were non-invasively and longitudinally imaged using NIRF lymphatic imaging after popliteal lymphadenectomy in mice. In a cohort of mice, B16F10 melanoma was inoculated on the dorsal aspect of the paw 27 days after lymphadenectomy to assess how drainage patterns affect metastasis.NIRF imaging demonstrates that, although lymphatic function and drainage patterns change significantly in early response to popliteal lymph node (PLN removal in mice, these changes are transient and regress dramatically due to a high regenerative capacity of the lymphatics and co-opting of collateral lymphatic pathways around the site of obstruction. Metastases followed the pattern of collateral pathways and could be detected proximal to the site of lymphadenectomy.Both lymphatic vessel regeneration and co-opting of contralateral vessels occur following lymphadenectomy, with contractile function restored within 13 days, providing a basis for preclinical and clinical investigations to hasten lymphatic repair and restore contractile lymphatic function after surgery to prevent cancer-acquired lymphedema. Patterns of cancer metastasis after lymphadenectomy were altered, consistent with patterns of re-directed lymphatic drainage.

  7. Experimental and Computational Insight Into Human Mesenchymal Stem Cell Paracrine Signaling and Heterocellular Coupling Effects on Cardiac Contractility and Arrhythmogenicity.

    Science.gov (United States)

    Mayourian, Joshua; Cashman, Timothy J; Ceholski, Delaine K; Johnson, Bryce V; Sachs, David; Kaji, Deepak A; Sahoo, Susmita; Hare, Joshua M; Hajjar, Roger J; Sobie, Eric A; Costa, Kevin D

    2017-08-04

    Myocardial delivery of human mesenchymal stem cells (hMSCs) is an emerging therapy for treating the failing heart. However, the relative effects of hMSC-mediated heterocellular coupling (HC) and paracrine signaling (PS) on human cardiac contractility and arrhythmogenicity remain unresolved. The objective is to better understand hMSC PS and HC effects on human cardiac contractility and arrhythmogenicity by integrating experimental and computational approaches. Extending our previous hMSC-cardiomyocyte HC computational model, we incorporated experimentally calibrated hMSC PS effects on cardiomyocyte L-type calcium channel/sarcoendoplasmic reticulum calcium-ATPase activity and cardiac tissue fibrosis. Excitation-contraction simulations of hMSC PS-only and combined HC+PS effects on human cardiomyocytes were representative of human engineered cardiac tissue (hECT) contractile function measurements under matched experimental treatments. Model simulations and hECTs both demonstrated that hMSC-mediated effects were most pronounced under PS-only conditions, where developed force increased ≈4-fold compared with non-hMSC-supplemented controls during physiological 1-Hz pacing. Simulations predicted contractility of isolated healthy and ischemic adult human cardiomyocytes would be minimally sensitive to hMSC HC, driven primarily by PS. Dominance of hMSC PS was also revealed in simulations of fibrotic cardiac tissue, where hMSC PS protected from potential proarrhythmic effects of HC at various levels of engraftment. Finally, to study the nature of the hMSC paracrine effects on contractility, proteomic analysis of hECT/hMSC conditioned media predicted activation of PI3K/Akt signaling, a recognized target of both soluble and exosomal fractions of the hMSC secretome. Treating hECTs with exosome-enriched, but not exosome-depleted, fractions of the hMSC secretome recapitulated the effects observed with hMSC conditioned media on hECT-developed force and expression of calcium

  8. A Small Molecule Inhibitor of Sarcomere Contractility Acutely Relieves Left Ventricular Outflow Tract Obstruction in Feline Hypertrophic Cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Joshua A Stern

    Full Text Available Hypertrophic cardiomyopathy (HCM is an inherited disease of the heart muscle characterized by otherwise unexplained thickening of the left ventricle. Left ventricular outflow tract (LVOT obstruction is present in approximately two-thirds of patients and substantially increases the risk of disease complications. Invasive treatment with septal myectomy or alcohol septal ablation can improve symptoms and functional status, but currently available drugs for reducing obstruction have pleiotropic effects and variable therapeutic responses. New medical treatments with more targeted pharmacology are needed, but the lack of preclinical animal models for HCM with LVOT obstruction has limited their development. HCM is a common cause of heart failure in cats, and a subset exhibit systolic anterior motion of the mitral valve leading to LVOT obstruction. MYK-461 is a recently-described, mechanistically novel small molecule that acts at the sarcomere to specifically inhibit contractility that has been proposed as a treatment for HCM. Here, we use MYK-461 to test whether direct reduction in contractility is sufficient to relieve LVOT obstruction in feline HCM. We evaluated mixed-breed cats in a research colony derived from a Maine Coon/mixed-breed founder with naturally-occurring HCM. By echocardiography, we identified five cats that developed systolic anterior motion of the mitral valve and LVOT obstruction both at rest and under anesthesia when provoked with an adrenergic agonist. An IV MYK-461 infusion and echocardiography protocol was developed to serially assess contractility and LVOT gradient at multiple MYK-461 concentrations. Treatment with MYK-461 reduced contractility, eliminated systolic anterior motion of the mitral valve and relieved LVOT pressure gradients in an exposure-dependent manner. Our findings provide proof of principle that acute reduction in contractility with MYK-461 is sufficient to relieve LVOT obstruction. Further, these studies

  9. Protective effects of anisodamine on cigarette smoke extract-induced airway smooth muscle cell proliferation and tracheal contractility

    International Nuclear Information System (INIS)

    Xu, Guang-Ni; Yang, Kai; Xu, Zu-Peng; Zhu, Liang; Hou, Li-Na; Qi, Hong; Chen, Hong-Zhuan; Cui, Yong-Yao

    2012-01-01

    Anisodamine, an antagonist of muscarinic acetylcholine receptors (mAChRs), has been used therapeutically to improve smooth muscle function, including microvascular, intestinal and airway spasms. Our previous studies have revealed that airway hyper-reactivity could be prevented by anisodamine. However, whether anisodamine prevents smoking-induced airway smooth muscle (ASM) cell proliferation remained unclear. In this study, a primary culture of rat ASM cells was used to evaluate an ASM phenotype through the ability of the cells to proliferate and express contractile proteins in response to cigarette smoke extract (CSE) and intervention of anisodamine. Our results showed that CSE resulted in an increase in cyclin D1 expression concomitant with the G0/G1-to-S phase transition, and high expression of M2 and M3. Functional studies showed that tracheal hyper-contractility accompanied contractile marker α-SMA high-expression. These changes, which occur only after CSE stimulation, were prevented and reversed by anisodamine, and CSE-induced cyclin D1 expression was significantly inhibited by anisodamine and the specific inhibitor U0126, BAY11-7082 and LY294002. Thus, we concluded that the protective and reversal effects and mechanism of anisodamine on CSE-induced events might involve, at least partially, the ERK, Akt and NF-κB signaling pathways associated with cyclin D1 via mAChRs. Our study validated that anisodamine intervention on ASM cells may contribute to anti-remodeling properties other than bronchodilation. -- Highlights: ► CSE induces tracheal cell proliferation, hyper-contractility and α-SMA expression. ► Anisodamine reverses CSE-induced tracheal hyper-contractility and cell proliferation. ► ERK, PI3K, and NF-κB pathways and cyclin D1 contribute to the reversal effect.

  10. Cardiac-specific catalase overexpression rescues anthrax lethal toxin-induced cardiac contractile dysfunction: role of oxidative stress and autophagy.

    Science.gov (United States)

    Kandadi, Machender R; Yu, Xuejun; Frankel, Arthur E; Ren, Jun

    2012-11-07

    Lethal and edema toxins secreted by Bacillus anthracis during anthrax infection were found to incite serious cardiovascular complications. However, the underlying mechanisms in anthrax lethal toxin-induced cardiac anomalies remain unknown. This study was designed to evaluate the impact of antioxidant enzyme catalase in anthrax lethal toxin-induced cardiomyocyte contractile dysfunction. Wild type (WT) and cardiac-specific catalase overexpression mice were challenged with lethal toxin (2 μg/g, intraperotineally (i.p.)). Cardiomyocyte contractile and intracellular Ca(2+) properties were assessed 18 h later using an IonOptix edge-detection system. Proteasome function was assessed using chymotrypsin-like and caspase-like activities. GFP-LC3 puncta and Western blot analysis were used to evaluate autophagy and protein ubiquitination. Lethal toxin exposure suppressed cardiomyocyte contractile function (suppressed peak shortening, maximal velocity of shortening/re-lengthening, prolonged duration of shortening/re-lengthening, and impaired intracellular Ca(2+) handling), the effects of which were alleviated by catalase. In addition, lethal toxin triggered autophagy, mitochondrial and ubiquitin-proteasome defects, the effects of which were mitigated by catalase. Pretreatment of cardiomyocytes from catalase mice with the autophagy inducer rapamycin significantly attenuated or ablated catalase-offered protection against lethal toxin-induced cardiomyocyte dysfunction. On the other hand, the autophagy inhibitor 3-MA ablated or significantly attenuated lethal toxin-induced cardiomyocyte contractile anomalies. Our results suggest that catalase is protective against anthrax lethal toxin-induced cardiomyocyte contractile and intracellular Ca(2+) anomalies, possibly through regulation of autophagy and mitochondrial function.

  11. Cardiac-specific catalase overexpression rescues anthrax lethal toxin-induced cardiac contractile dysfunction: role of oxidative stress and autophagy

    Directory of Open Access Journals (Sweden)

    Kandadi Machender R

    2012-11-01

    Full Text Available Abstract Background Lethal and edema toxins secreted by Bacillus anthracis during anthrax infection were found to incite serious cardiovascular complications. However, the underlying mechanisms in anthrax lethal toxin-induced cardiac anomalies remain unknown. This study was designed to evaluate the impact of antioxidant enzyme catalase in anthrax lethal toxin-induced cardiomyocyte contractile dysfunction. Methods Wild type (WT and cardiac-specific catalase overexpression mice were challenged with lethal toxin (2 μg/g, intraperotineally (i.p.. Cardiomyocyte contractile and intracellular Ca2+ properties were assessed 18 h later using an IonOptix edge-detection system. Proteasome function was assessed using chymotrypsin-like and caspase-like activities. GFP-LC3 puncta and Western blot analysis were used to evaluate autophagy and protein ubiquitination. Results Lethal toxin exposure suppressed cardiomyocyte contractile function (suppressed peak shortening, maximal velocity of shortening/re-lengthening, prolonged duration of shortening/re-lengthening, and impaired intracellular Ca2+ handling, the effects of which were alleviated by catalase. In addition, lethal toxin triggered autophagy, mitochondrial and ubiquitin-proteasome defects, the effects of which were mitigated by catalase. Pretreatment of cardiomyocytes from catalase mice with the autophagy inducer rapamycin significantly attenuated or ablated catalase-offered protection against lethal toxin-induced cardiomyocyte dysfunction. On the other hand, the autophagy inhibitor 3-MA ablated or significantly attenuated lethal toxin-induced cardiomyocyte contractile anomalies. Conclusions Our results suggest that catalase is protective against anthrax lethal toxin-induced cardiomyocyte contractile and intracellular Ca2+ anomalies, possibly through regulation of autophagy and mitochondrial function.

  12. Protective effects of anisodamine on cigarette smoke extract-induced airway smooth muscle cell proliferation and tracheal contractility

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Guang-Ni; Yang, Kai; Xu, Zu-Peng; Zhu, Liang; Hou, Li-Na; Qi, Hong; Chen, Hong-Zhuan, E-mail: hongzhuan_chen@hotmail.com; Cui, Yong-Yao, E-mail: yongyaocui@yahoo.com.cn

    2012-07-01

    Anisodamine, an antagonist of muscarinic acetylcholine receptors (mAChRs), has been used therapeutically to improve smooth muscle function, including microvascular, intestinal and airway spasms. Our previous studies have revealed that airway hyper-reactivity could be prevented by anisodamine. However, whether anisodamine prevents smoking-induced airway smooth muscle (ASM) cell proliferation remained unclear. In this study, a primary culture of rat ASM cells was used to evaluate an ASM phenotype through the ability of the cells to proliferate and express contractile proteins in response to cigarette smoke extract (CSE) and intervention of anisodamine. Our results showed that CSE resulted in an increase in cyclin D1 expression concomitant with the G0/G1-to-S phase transition, and high expression of M2 and M3. Functional studies showed that tracheal hyper-contractility accompanied contractile marker α-SMA high-expression. These changes, which occur only after CSE stimulation, were prevented and reversed by anisodamine, and CSE-induced cyclin D1 expression was significantly inhibited by anisodamine and the specific inhibitor U0126, BAY11-7082 and LY294002. Thus, we concluded that the protective and reversal effects and mechanism of anisodamine on CSE-induced events might involve, at least partially, the ERK, Akt and NF-κB signaling pathways associated with cyclin D1 via mAChRs. Our study validated that anisodamine intervention on ASM cells may contribute to anti-remodeling properties other than bronchodilation. -- Highlights: ► CSE induces tracheal cell proliferation, hyper-contractility and α-SMA expression. ► Anisodamine reverses CSE-induced tracheal hyper-contractility and cell proliferation. ► ERK, PI3K, and NF-κB pathways and cyclin D1 contribute to the reversal effect.

  13. Right Diaphragm Spontaneous Rupture: A Surgical Approach

    Directory of Open Access Journals (Sweden)

    Duilio Divisi

    2011-01-01

    Full Text Available We present a case of spontaneous rupture of the diaphragm, characterized by nonspecific symptoms. The rapid diagnosis and appropriate surgical approach led to a positive resolution of the pathology.

  14. Spontaneous cecal perforation secondary to acute fulminant ...

    African Journals Online (AJOL)

    Spontaneous cecal perforation secondary to acute fulminant gastroenteritis: report of a rare case. Duvuru Ram, Vilvapathy S. Karthikeyan, Sarath C. Sistla, Sheik M. Ali, Parnandi Sridhar, Nagarajan Rajkumar ...

  15. Spontaneous Trait Inferences on Social Media.

    Science.gov (United States)

    Levordashka, Ana; Utz, Sonja

    2017-01-01

    The present research investigates whether spontaneous trait inferences occur under conditions characteristic of social media and networking sites: nonextreme, ostensibly self-generated content, simultaneous presentation of multiple cues, and self-paced browsing. We used an established measure of trait inferences (false recognition paradigm) and a direct assessment of impressions. Without being asked to do so, participants spontaneously formed impressions of people whose status updates they saw. Our results suggest that trait inferences occurred from nonextreme self-generated content, which is commonly found in social media updates (Experiment 1) and when nine status updates from different people were presented in parallel (Experiment 2). Although inferences did occur during free browsing, the results suggest that participants did not necessarily associate the traits with the corresponding status update authors (Experiment 3). Overall, the findings suggest that spontaneous trait inferences occur on social media. We discuss implications for online communication and research on spontaneous trait inferences.

  16. Spontane abdominale arteriovenøse fistler

    DEFF Research Database (Denmark)

    Flarup, S; Lindholt, Jes Sanddal

    1997-01-01

    Spontaneous arteriovenous fistulas between major abdominal vessels (AAVF) complicates about 1% of abdominal aortic aneurysms. AAVF produces severe circulatory disturbances with high operative mortality. Preoperative diagnosis is important but difficult due to the varied nature of presentation. Fo...

  17. Depressive disorder and grief following spontaneous abortion.

    Science.gov (United States)

    Kulathilaka, Susil; Hanwella, Raveen; de Silva, Varuni A

    2016-04-12

    Abortion is associated with moderate to high risk of psychological problems such as depression, use of alcohol or marijuana, anxiety, depression and suicidal behaviours. The increased risk of depression after spontaneous abortion in Asian populations has not been clearly established. Only a few studies have explored the relationship between grief and depression after abortion. A study was conducted to assess the prevalence and risk factors of depressive disorder and complicated grief among women 6-10 weeks after spontaneous abortion and compare the risk of depression with pregnant women attending an antenatal clinic. Spontaneous abortion group consisted of women diagnosed with spontaneous abortion by a Consultant Obstetrician. Women with confirmed or suspected induced abortion were excluded. The comparison group consisted of randomly selected pregnant, females attending the antenatal clinics of the two hospitals. Diagnosis of depressive disorder was made according to ICD-10 clinical criteria based on a structured clinical interview. This assessment was conducted in both groups. The severity of depressive symptoms were assessed using the Patients Health Questionnaire (PHQ-9). Grief was assessed using the Perinatal Grief Scale which was administered to the women who had experienced spontaneous abortion. The sample consisted of 137 women in each group. The spontaneous abortion group (mean age 30.39 years (SD = 6.38) were significantly older than the comparison group (mean age 28.79 years (SD = 6.26)). There were more females with ≥10 years of education in the spontaneous abortion group (n = 54; SD = 39.4) compared to the comparison group (n = 37; SD = 27.0). The prevalence of depression in the spontaneous abortion group was 18.6 % (95 CI, 11.51-25.77). The prevalence of depression in the comparison group was 9.5 % (95 CI, 4.52-14.46). Of the 64 women fulfilling criteria for grief, 17 (26.6 %) also fulfilled criteria for a depressive episode. The relative risk of

  18. Postmenopausal spontaneous uterine perforation: Case report

    Science.gov (United States)

    İşlek Seçen, Elçin; Ağış, Hilal; Altunkaya, Canan; Avşar, Ayşe Filiz

    2015-01-01

    Spontaneous uterine rupture and generalized peritonitis caused by pyometra occurs rarely with high morbidity and mortality. A correct and definite diagnosis can be made with laparotomy or laparoscopy. The clinical findings of perforated pyometra are similar to perforation of the gastrointestinal tract and gynecologic symptoms are less frequent, which makes preoperative diagnosis difficult. We report a case of a patient aged 82 years who underwent surgery for spontaneous uterine rupture and generalized peritonitis as a result of pyometra. PMID:28913055

  19. Endometriosis-related spontaneous diaphragmatic rupture.

    Science.gov (United States)

    Triponez, Frédéric; Alifano, Marco; Bobbio, Antonio; Regnard, Jean-François

    2010-10-01

    Non-traumatic, spontaneous diaphragmatic rupture is a rare event whose pathophysiology is not known. We report the case of endometriosis-related spontaneous rupture of the right diaphragm with intrathoracic herniation of the liver, gallbladder and colon. We hypothesize that the invasiveness of endometriotic tissue caused diaphragm fragility, which finally lead to its complete rupture without traumatic event. The treatment consisted of a classical management of diaphragmatic rupture, with excision of the endometriotic nodule followed by medical ovarian suppression for six months.

  20. Spontaneous regression of metastatic Merkel cell carcinoma.

    LENUS (Irish Health Repository)

    Hassan, S J

    2010-01-01

    Merkel cell carcinoma is a rare aggressive neuroendocrine carcinoma of the skin predominantly affecting elderly Caucasians. It has a high rate of local recurrence and regional lymph node metastases. It is associated with a poor prognosis. Complete spontaneous regression of Merkel cell carcinoma has been reported but is a poorly understood phenomenon. Here we present a case of complete spontaneous regression of metastatic Merkel cell carcinoma demonstrating a markedly different pattern of events from those previously published.

  1. Spontaneous intracranial epidural hematoma during rivaroxaban treatment

    Energy Technology Data Exchange (ETDEWEB)

    Ruschel, Leonardo Gilmone; Rego, Felipe Marques Monteiro do; Milano, Jeronimo Buzetti; Jung, Gustavo Simiano; Silva Junior, Luis Fernando; Ramina, Ricardo, E-mail: leonardoruschel@yahoo.com.br [Instituto de Neurologia de Curitiba (INC), Curitiba, PR (Brazil)

    2016-11-15

    According to our research, this is the first case described in the literature of spontaneous intracranial epidural hematoma secondary to the use of Xarelto®. Spontaneous intracranial epidural hematomas are rarely described in the literature. They are associated with infectious diseases of the skull, coagulation disorders, vascular malformations of the dura mater and metastasis to the skull. Long-term post-marketing monitoring and independent reports will probably detect the full spectrum of hemorrhagic complications of the use of rivaroxaban. (author)

  2. Spontaneous intracranial epidural hematoma during rivaroxaban treatment.

    Science.gov (United States)

    Ruschel, Leonardo Gilmone; Rego, Felipe Marques Monteiro do; Milano, Jerônimo Buzetti; Jung, Gustavo Simiano; Silva, Luis Fernando; Ramina, Ricardo

    2016-11-01

    According to our research, this is the first case described in the literature of spontaneous intracranial epidural hematoma secondary to the use of Xareltor. Spontaneous intracranial epidural hematomas are rarely described in the literature. They are associated with infectious diseases of the skull, coagulation disorders, vascular malformations of the dura mater and metastasis to the skull. Long-term post-marketing monitoring and independent reports will probably detect the full spectrum of hemorrhagic complications of the use of rivaroxaban.

  3. FEL gain optimisation and spontaneous radiation

    Energy Technology Data Exchange (ETDEWEB)

    Bali, L.M.; Srivastava, A.; Pandya, T.P. [Lucknow Univ. (India)] [and others

    1995-12-31

    Colson have evaluated FEL gains for small deviations from perfect electron beam injection, with radiation of the same polarisation as that of the wiggler fields. We find that for optimum gain the polarisation of the optical field should be the same as that of the spontaneous emission under these conditions. With a helical wiggler the axial oscillations resulting from small departures from perfect electron beam injection lead to injection dependent unequal amplitudes and phases of the spontaneous radiation in the two transverse directions. Viewed along the axis therefore the spontaneous emission is elliptically polarised. The azimuth of the ellipse varies with the difference of phase of the two transverse components of spontaneous emission but the eccentricity remains the same. With planar wigglers the spontaneous emission viewed in the axial direction is linearly polarised, again with an injection dependent azimuth. For optimum coherent gain of a radiation field its polarisation characteristics must be the same as those of the spontaneous radiation with both types of wiggler. Thus, with a helical wiggler and the data reported earlier, an increase of 10% in the FEL gain at the fundamental frequency and of 11% at the fifth harmonic has been calculated in the small gain per pass limit. Larger enhancements in gain may result from more favourable values of input parameters.

  4. Adenylyl cyclase-mediated effects contribute to increased Isoprenaline-induced cardiac contractility in TRPM4-deficient mice.

    Science.gov (United States)

    Uhl, Sebastian; Mathar, Ilka; Vennekens, Rudi; Freichel, Marc

    2014-09-01

    TRPM4 and TRPM5 proteins belong to the Transient Receptor Potential (TRP) ion channel family and form Ca(2+)-activated nonselective cation channels. Recently we showed a significant increase of Isoprenaline-induced inotropy in TRPM4-deficient (Trpm4(-/-)) mice. This is caused by increased Ca(2+) entry via L-type calcium channels due to faster action potential repolarization in Trpm4(-/-) ventricular myocytes [Mathar et al., 2013]. Here, we investigated the contribution of various steps of the β-adrenergic signalling cascade to the augmented positive inotropic response in the absence of TRPM4, and whether the closely related TRPM5 additively contributes to this process using TRPM4/TRPM5-double deficient (Trpm4/Trpm5((-/-)2)) mice. We performed contractility measurements on isolated papillary muscles from wild type, Trpm4(-/-) and Trpm4/Trpm5((-/-)2) mice. As shown in Trpm4(-/-) mice, Isoprenaline-induced inotropy in Trpm4/Trpm5((-/-)2) papillary muscles was significantly increased compared to wild type, whereas basal, frequency- and Ca(2+)-dependent contractility was unaltered. Equivalent to Isoprenaline, activation of adenylyl cyclase using Forskolin led to a significantly increased twitch force in Trpm4(-/-) heart preparations whereas the Isoprenaline-mediated increase in cAMP level was comparable to wild type mice. Notably, the positive inotropic response evoked by phosphodiesterase inhibition with 3-isobutyl-1-methylxanthine (IBMX) was unchanged between both genotypes. Furthermore, experiments performed with increasing concentrations of IBMX after prestimulation with Forskolin and vice versa did not provide evidence that the increased β-adrenergic positive inotropic response in TRPM4-deficient papillary muscles is due to differences in accumulation of cAMP. Compared to inhibition of phosphodiesterase, the rise of intracellular cAMP by activating adenylyl cyclase is accompanied by ATP breakdown. To test the relevance of TRPM4 during forced ATP consumption we

  5. Dietary fat influences the expression of contractile and metabolic genes in rat skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Wataru Mizunoya

    Full Text Available Dietary fat plays a major role in obesity, lipid metabolism, and cardiovascular diseases. To determine whether the intake of different types of dietary fats affect the muscle fiber types that govern the metabolic and contractile properties of the skeletal muscle, we fed male Wistar rats with a 15% fat diet derived from different fat sources. Diets composed of soybean oil (n-6 polyunsaturated fatty acids (PUFA-rich, fish oil (n-3 PUFA-rich, or lard (low in PUFAs were administered to the rats for 4 weeks. Myosin heavy chain (MyHC isoforms were used as biomarkers to delineate the skeletal muscle fiber types. Compared with soybean oil intake, fish oil intake showed significantly lower levels of the fast-type MyHC2B and higher levels of the intermediate-type MyHC2X composition in the extensor digitorum longus (EDL muscle, which is a fast-type dominant muscle. Concomitantly, MyHC2X mRNA levels in fish oil-fed rats were significantly higher than those observed in the soybean oil-fed rats. The MyHC isoform composition in the lard-fed rats was an intermediate between that of the fish oil and soybean oil-fed rats. Mitochondrial uncoupling protein 3, pyruvate dehydrogenase kinase 4, and porin mRNA showed significantly upregulated levels in the EDL of fish oil-fed rats compared to those observed in soybean oil-fed and lard-fed rats, implying an activation of oxidative metabolism. In contrast, no changes in the composition of MyHC isoforms was observed in the soleus muscle, which is a slow-type dominant muscle. Fatty acid composition in the serum and the muscle was significantly influenced by the type of dietary fat consumed. In conclusion, dietary fat affects the expression of genes related to the contractile and metabolic properties in the fast-type dominant skeletal muscle, where the activation of oxidative metabolism is more pronounced after fish oil intake than that after soybean oil intake.

  6. Controlled chaos: three-dimensional kinematics, fiber histochemistry, and muscle contractile dynamics of autotomized lizard tails.

    Science.gov (United States)

    Higham, Timothy E; Lipsett, Kathryn R; Syme, Douglas A; Russell, Anthony P

    2013-01-01

    The ability to shed an appendage occurs in both vertebrates and invertebrates, often as a tactic to avoid predation. The tails of lizards, unlike most autotomized body parts of animals, exhibit complex and vigorous movements once disconnected from the body. Despite the near ubiquity of autotomy across groups of lizards and the fact that this is an extraordinary event involving the self-severing of the spinal cord, our understanding of why and how tails move as they do following autotomy is sparse. We herein explore the histochemistry and physiology of the tail muscles of the leopard gecko (Eublepharis macularius), a species that exhibits vigorous and variable tail movements following autotomy. To confirm that the previously studied tail movements of this species are generally representative of geckos and therefore suitable for in-depth muscle studies, we quantified the three-dimensional kinematics of autotomized tails in three additional species. The movements of the tails of all species were generally similar and included jumps, flips, and swings. Our preliminary analyses suggest that some species of gecko exhibit short but high-frequency movements, whereas others exhibit larger-amplitude but lower-frequency movements. We then compared the ATPase and oxidative capacity of muscle fibers and contractile dynamics of isolated muscle bundles from original tails, muscle from regenerate tails, and fast fibers from an upper limb muscle (iliofibularis) of the leopard gecko. Histochemical analysis revealed that more than 90% of the fibers in original and regenerate caudal muscles had high ATPase but possessed a superficial layer of fibers with low ATPase and high oxidative capacity. We found that contraction kinetics, isometric force, work, power output, and the oscillation frequency at which maximum power was generated were lowest in the original tail, followed by the regenerate tail and then the fast fibers of the iliofibularis. Muscle from the original tail exhibited

  7. Comparative analysis of mouse skeletal muscle fibre type composition and contractile responses to calcium channel blocker

    Directory of Open Access Journals (Sweden)

    Järvilehto Matti

    2005-02-01

    Full Text Available Abstract Background In this study, we examined the correlation between excitation-contraction coupling characteristics and skeletal muscle fibre type by (1 localizing the distribution of dihydropyridine receptor (DHPR protein and (2 comparing the effect of DHPR blocker on muscles with different fibre type composition, in order to better understand the differences between contractile phenotypes of fibres and to explain the contradictory reports to date on the interaction of dihydropyridines with skeletal muscle isoform of DHPR. Results Histochemical experiments revealed that fluorophore conjugated dihydropyridines stain selectively the membranes of muscle fibres. The staining was most evident in type IIA fibres. The major fibre type in gluteus and femoris, revealed by mATPase staining, was IIA (45.0 and 38.1 %, respectively. In gastrocnemius the content of IIA fibres was 22.7 %. Contraction forces before and after the addition of blocker for the three muscles investigated were: gluteus 0.075 ± 0.017 N vs. 0.052 ± 0.011 N, femoris 0.045 ± 0.005 N vs. 0.033 ± 0.005 N and gastrocnemius 0.089 ± 0.016 N vs. 0.075 ± 0.014 N, respectively. The attenuation of contraction force proportional to the cross-sectional area of the muscle was significantly (P = 0.023 higher in gluteus (28.3 ± 3.5 % and femoris (27.6 ± 3.2 % as compared to gastrocnemius (16.1 ± 2.5 %. However, no significant change in the control measurements was observed ruling out the possibility of fatigue. Conclusion The results indicate that the attenuation of the contraction force was largest in muscles with a high percentage of type IIA fibres. This supports our finding that the abundance of dihydropyridine receptors of IIA fibres outnumbers that in the other fibre types. The present data show that the correlation of density of dihydropyridine receptors can be one of the important factors influencing the overall contractile properties of the muscle and for its part explain the

  8. Spontaneous body movements in spatial cognition

    Directory of Open Access Journals (Sweden)

    Sergiu eTcaci Popescu

    2012-05-01

    Full Text Available People often perform spontaneous body movements during spatial tasks such as giving complex directions or orienting themselves on maps. How are these spontaneous gestures related to spatial problem-solving? We measured spontaneous movements during a perspective-taking task inspired by map reading. Analyzing the motion data to isolate rotation and translation components of motion in specific geometric relation to the task, we found out that most participants executed spontaneous miniature rotations of the head that were significantly related to the main task parameter. These head rotations were as if participants were trying to align themselves with the orientation on the map either in the image plane or on the ground plane, but with tiny amplitudes, typically below 1% of the actual movements. Our results are consistent with a model of sensorimotor prediction driving spatial reasoning. The efference copy of planned movements triggers this prediction mechanism. The movements themselves may then be mostly inhibited; the small spontaneous gestures that we measure are the visible traces of these planned but inhibited actions.

  9. Bilateral spontaneous rupture of 'hale' kidneys

    International Nuclear Information System (INIS)

    Naumov, N.; Zozikov, B.; Otzetov, A.; Kamenova, M.; Martinova, F.; Kalyonski, R.

    2002-01-01

    A rare case of spontaneous bilateral rupture of the kidneys, occurring consecutively over a one-year period in a young male patient with 'hale' kidneys until then, is described. The patient's past history and thorough examination performed do not justify to assign the case under the heading of some of the etiological factors as the underlying cause of spontaneous kidney rupture. The literature survey on spontaneous bilateral non-tumor ruptures of kidneys shows that over a 20-year period, only 3 cases of bilateral spontaneous ruptures have been reported. It is pointed out that panarteritis nodosa followed by hemorrhagic fever with renal syndrome is the commonest underlying cause of such ruptures. Clinically spontaneous ruptures become manifest with emergency condition presenting severe renal colic, impaired to serious general condition, often with acute abdomen and hemodynamic breakdown, and no past history evidence of renal disease or injury. In the initial phase diagnosing is not always easy; it is usually made on the ground of physical examination and the full range of imaging studies used in urological practice and during operative treatment. Emphasis is laid on the fact that the imaging methods are not invariably sufficient to identify the exact etiological factor giving rise to such a severe condition, but nevertheless these methods have an essential practical bearing on diagnosing a rupture. (authors)

  10. Surgical management of spontaneous hypertensive brainstem hemorrhage

    Directory of Open Access Journals (Sweden)

    Bal Krishna Shrestha

    2015-09-01

    Full Text Available Spontaneous hypertensive brainstem hemorrhage is the spontaneous brainstem hemorrhage associated with long term hypertension but not having definite focal or objective lesion. It is a catastrophic event which has a poor prognosis and usually managed conservatively. It is not uncommon, especially in eastern Asian populations, accounting approximately for 10% of the intracerebral hemorrhage. Before the advent of computed tomography, the diagnosis of brainstem hemorrhage was usually based on the clinical picture or by autopsy and believed to be untreatable via surgery. The introduction of computed tomography permitted to categorize the subtypes of brainstem hemorrhage with more predicted outcome. Continuous ongoing developments in the stereotactic surgery and microsurgery have added more specific surgical management in these patients. However, whether to manage conservatively or promptly with surgical evacuation of hematoma is still a controversy. Studies have shown that an accurate prognostic assessment based on clinical and radiological features on admission is critical for establishing a reasonable therapeutic approach. Some authors have advocate conservative management, whereas others have suggested the efficacy of surgical treatment in brainstem hemorrhage. With the widening knowledge in microsurgical techniques as well as neuroimaging technology, there seems to have more optimistic hope of surgical management of spontaneous hypertensive brainstem hemorrhage for better prognosis. Here we present five cases of severe spontaneous hypertensive brainstem hemorrhage patients who had undergone surgery; and explore the possibilities of surgical management in patients with the spontaneous hypertensive brainstem hemorrhage.

  11. Cursed lamp: the problem of spontaneous abortion.

    Science.gov (United States)

    Simkulet, William

    2017-08-09

    Many people believe human fetuses have the same moral status as adult human persons, that it is wrong to allow harm to befall things with this moral status, and thus voluntary, induced abortion is seriously morally wrong. Recently, many prochoice theorists have argued that this antiabortion stance is inconsistent; approximately 60% of human fetuses die from spontaneous abortion, far more than die from induced abortion, so if antiabortion theorists really believe that human fetuses have significant moral status, they have strong moral obligations to oppose spontaneous abortion. Yet, few antiabortion theorists devote any effort to doing so. Many prochoice theorists argue that to resolve this inconsistency, antiabortion theorists should abandon their opposition to induced abortion. Here, I argue that those who do not abandon their opposition to induced abortion but continue to neglect spontaneous abortion act immorally. Aristotle argues that moral responsibility requires both control and awareness; I argue that once an antiabortion theorist becomes aware of the frequency of spontaneous abortion, they have a strong moral obligation to redirect their efforts towards combating spontaneous abortion; failure to do so is morally monstrous. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  12. Pro-contractile action of the Na,K-ATPase/Src-kinase signaling pathway in the vascular wall

    DEFF Research Database (Denmark)

    Bouzinova, Elena; Aalkjær, Christian; Matchkov, Vladimir

    Aim: Na,K-ATPase is essential for maintaining the transmembrane ion gradient and might initiate various intracellular signaling. These signals possibly act through a modification of the local ion concentrations or via Src-kinase activation. It is known that inhibition of the α-2 isoform of Na...... of ouabain. Here we demonstrate results of our research on the mechanisms involved in the modulation of vascular wall contractility by ouabain-sensitive Na,K-ATPase. Methods: The experiments were performed using rat mesenteric arteries in isometric myograph conditions. To inhibit kinase activity a Src......-family selective tyrosine kinase inhibitor, PP2, and pNaKtide - a membrane-permeable small peptide which antagonizes ouabain-induced activation of Src-kinase were used. Results: The pro-contractile action of ouabain is associated with activation of Src. This is supported by Western blot analyses showing activation...

  13. Non-Invasive Acoustical sensing of Drug-Induced Effects on the Contractile Machinery of Human Cardiomyocyte Clusters.

    Directory of Open Access Journals (Sweden)

    Angelika Kunze

    Full Text Available There is an urgent need for improved models for cardiotoxicity testing. Here we propose acoustic sensing applied to beating human cardiomyocyte clusters for non-invasive, surrogate measuring of the QT interval and other characteristics of the contractile machinery. In experiments with the acoustic method quartz crystal microbalance with dissipation monitoring (QCM-D, the shape of the recorded signals was very similar to the extracellular field potential detected in electrochemical experiments, and the expected changes of the QT interval in response to addition of conventional drugs (E-4031 or nifedipine were observed. Additionally, changes in the dissipation signal upon addition of cytochalasin D were in good agreement with the known, corresponding shortening of the contraction-relaxation time. These findings suggest that QCM-D has great potential as a tool for cardiotoxicological screening, where effects of compounds on the cardiomyocyte contractile machinery can be detected independently of whether the extracellular field potential is altered or not.

  14. Non-Invasive Acoustical sensing of Drug-Induced Effects on the Contractile Machinery of Human Cardiomyocyte Clusters

    Science.gov (United States)

    Kunze, Angelika; Steel, Daniella; Dahlenborg, Kerstin; Sartipy, Peter; Svedhem, Sofia

    2015-01-01

    There is an urgent need for improved models for cardiotoxicity testing. Here we propose acoustic sensing applied to beating human cardiomyocyte clusters for non-invasive, surrogate measuring of the QT interval and other characteristics of the contractile machinery. In experiments with the acoustic method quartz crystal microbalance with dissipation monitoring (QCM-D), the shape of the recorded signals was very similar to the extracellular field potential detected in electrochemical experiments, and the expected changes of the QT interval in response to addition of conventional drugs (E-4031 or nifedipine) were observed. Additionally, changes in the dissipation signal upon addition of cytochalasin D were in good agreement with the known, corresponding shortening of the contraction-relaxation time. These findings suggest that QCM-D has great potential as a tool for cardiotoxicological screening, where effects of compounds on the cardiomyocyte contractile machinery can be detected independently of whether the extracellular field potential is altered or not. PMID:25961711

  15. Integrated Analysis of Contractile Kinetics, Force Generation, and Electrical Activity in Single Human Stem Cell-Derived Cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Jan David Kijlstra

    2015-12-01

    Full Text Available The quantitative analysis of cardiomyocyte function is essential for stem cell-based approaches for the in vitro study of human cardiac physiology and pathophysiology. We present a method to comprehensively assess the function of single human pluripotent stem cell-derived cardiomyocyte (hPSC-CMs through simultaneous quantitative analysis of contraction kinetics, force generation, and electrical activity. We demonstrate that statistical analysis of movies of contracting hPSC-CMs can be used to quantify changes in cellular morphology over time and compute contractile kinetics. Using a biomechanical model that incorporates substrate stiffness, we calculate cardiomyocyte force generation at single-cell resolution and validate this approach with conventional traction force microscopy. The addition of fluorescent calcium indicators or membrane potential dyes allows the simultaneous analysis of contractility and calcium handling or action potential morphology. Accordingly, our approach has the potential for broad application in the study of cardiac disease, drug discovery, and cardiotoxicity screening.

  16. α-Actinin links extracellular matrix rigidity-sensing contractile units with periodic cell-edge retractions

    Science.gov (United States)

    Meacci, Giovanni; Wolfenson, Haguy; Liu, Shuaimin; Stachowiak, Matthew R.; Iskratsch, Thomas; Mathur, Anurag; Ghassemi, Saba; Gauthier, Nils; Tabdanov, Erdem; Lohner, James; Gondarenko, Alexander; Chander, Ashok C.; Roca-Cusachs, Pere; O’Shaughnessy, Ben; Hone, James; Sheetz, Michael P.

    2016-01-01

    During spreading and migration, the leading edges of cells undergo periodic protrusion–retraction cycles. The functional purpose of these cycles is unclear. Here, using submicrometer polydimethylsiloxane pillars as substrates for cell spreading, we show that periodic edge retractions coincide with peak forces produced by local contractile units (CUs) that assemble and disassemble along the cell edge to test matrix rigidity. We find that, whereas actin rearward flow produces a relatively constant force inward, the peak of local contractile forces by CUs scales with rigidity. The cytoskeletal protein α-actinin is shared between these two force-producing systems. It initially localizes to the CUs and subsequently moves inward with the actin flow. Knockdown of α-actinin causes aberrant rigidity sensing, loss of CUs, loss of protrusion–retraction cycles, and, surprisingly, enables the cells to proliferate on soft matrices. We present a model based on these results in which local CUs drive rigidity sensing and adhesion formation. PMID:27122603

  17. Endothelium protectant and contractile effects of the antivaricose principle escin in rat aorta.

    Science.gov (United States)

    Carrasco, Omar F; Vidrio, Horacio

    2007-07-01

    The triterpene saponin escin is the active component of the extract of seeds of Aesculus hippocastanum used in the treatment of chronic venous insufficiency. Escin is also used experimentally to increase membrane permeability in isolated cells. Since endothelial dysfunction is postulated to be involved in venous insufficiency, the possible endothelium-protectant effect of escin was explored in rat aortic rings, a model widely used to study such effects with cardiovascular agents. Escin enhanced endothelium-dependent relaxation induced by acetylcholine when such relaxation had been reduced by exposure to the superoxide ion generator pyrogallol. This effect was attributed to enhanced nitric oxide production by endothelial nitric oxide synthase, a calcium-dependent enzyme, activated by the increased endothelial cell permeability to calcium induced by escin. Another effect of escin thought to contribute to its therapeutic activity is its ability to produce venous contraction. The compound was found to induce concentration-related contraction also in rat aortic rings. This response was partially inhibited by removal of the endothelium or by preincubation with indomethacin, and was completely abolished by incubation in a calcium-free perfusion fluid. Contraction was considered to be due mainly to the aforementioned effect on calcium permeability, with some mediation by release of endothelial vasoconstrictor prostanoids. It was concluded that, in rat aorta, escin possesses an endothelium-protectant action and a direct contractile effect. The former could contribute to its beneficial effect in the treatment of venous insufficiency, while the latter could constitute a limiting side effect.

  18. [Heart sound recognition algorithm based on PNN for evaluating cardiac contractility change trend].

    Science.gov (United States)

    Guo, Xingming; Yan, Yan; Yao, Xiaoshuai; Xiao, Shouzhong

    2006-10-01

    This paper discusses the recognition of heart sound for evaluating the cardiac contractility change trend, which includes heart sound samples recorded at different exercise condition. Especially, focused on the recognition of heart sound recorded after high intensity exercise workload. The algorithm proposed consisted of two correlative methods. The first was to recognize heart sound recorded at rest and after low intensity exercise workloads by probabilistic neural network and the second was to recognize heart sound recorded after high intensity exercise workloads based on the characteristic of heart sound. Both methods have two consecutive phases. Firstly, all peaks, including the peaks of both heart sounds and noise, are marked by a repetitive threshold detecting algorithm. Secondly, probabilistic neural network is employed to classify the peaks detected in the first phase into Si, S2, and noise. Finally, the performance of the algorithm was evaluated using 45 digital heart sound recordings including normal and abnormal heart sound, which were recorded at rest and after low intensity exercise workloads, and 28 digital heart sound recordings recorded after high intensity exercise workloads. The results showed that over 94% of heart sound samples were classified and recognized correctly. Moreover, the reasons for the wrong classification, of which omitting and misdetection are two main problems, are also discussed and solutions are proposed. So this method can be improved and refined in following studies. In conclusion, this algorithm is a reliable approach to detect and classify heart sounds, providing a solid basis for further heart sound analysis.

  19. Multiple effects of sibutramine on ejaculation and on vas deferens and seminal vesicle contractility

    International Nuclear Information System (INIS)

    Nojimoto, Fernanda D.; Piffer, Renata C.; Kiguti, Luiz Ricardo de A.; Lameu, Claudiana; Camargo, Antonio C.M. de; Pereira, Oduvaldo C.M.; Pupo, Andre S.

    2009-01-01

    Sibutramine is an inhibitor of norepinephrine and 5-HT reuptake largely used in the management of obesity. Although a fairly safe drug, postmarketing adverse effects of sibutramine were reported including abnormal ejaculation in men. This study investigates the effects of sibutramine on ejaculation and vas deferens and seminal vesicle contractility. Adult male rats received sibutramine (5; 20; or 50 mg kg -1 , ip) and after 60 min were exposed to receptive females for determination of ejaculation parameters. The vasa deferentia and seminal vesicles of untreated rats were mounted in isolated organ baths for recording of isometric contractions and HEK293 cells loaded with fluorescent calcium indicator were used to measure intracellular Ca 2+ transients. Sibutramine 5 and 20 mg kg -1 reduced ejaculation latency whereas 50 mg kg -1 increased ejaculation latency. Sibutramine 3 to 30 μM greatly increased the sensitivity of the seminal vesicle and vas deferens to norepinephrine, but at concentrations higher than 10 μM there were striking depressions of maximal contractions induced by norepinephrine, carbachol and CaCl 2 . In HEK293 cells, sibutramine 10 to 100 μM inhibited intracellular Ca 2+ transients induced by carbachol. Depending on the doses, sibutramine either facilitates or inhibits ejaculation. Apart from its actions in the central nervous system, facilitation of ejaculation may result from augmented sensitivity of smooth muscles to norepinephrine while reductions of intracellular Ca 2+ may be involved in the delayed ejaculation observed with high doses of sibutramine.

  20. Simulation of the contractile response of cells on an array of micro-posts.

    LENUS (Irish Health Repository)

    McGarry, J P

    2009-09-13

    A bio-chemo-mechanical model has been used to predict the contractile responses of smooth cells on a bed of micro-posts. Predictions obtained for smooth muscle cells reveal that, by converging onto a single set of parameters, the model captures all of the following responses in a self-consistent manner: (i) the scaling of the force exerted by the cells with the number of posts; (ii) actin distributions within the cells, including the rings of actin around the micro-posts; (iii) the curvature of the cell boundaries between the posts; and (iv) the higher post forces towards the cell periphery. Similar correspondences between predictions and measurements have been demonstrated for fibroblasts and mesenchymal stem cells once the maximum stress exerted by the stress fibre bundles has been recalibrated. Consistent with measurements, the model predicts that the forces exerted by the cells will increase with both increasing post stiffness and cell area (or equivalently, post spacing). In conjunction with previous assessments, these findings suggest that this framework represents an important step towards a complete model for the coupled bio-chemo-mechanical responses of cells.

  1. Distensibility of portacaval shunts in portal hypertensive cats: index of contractility model.

    Science.gov (United States)

    Inglés, A C; Legare, D J; Lautt, W W

    1994-06-01

    Complete shunting of portal blood flow through portacaval shunts was obtained using a constrictor around the portal vein to gradually produce a total occlusion. After 4 weeks, acute experiments were conducted in anesthetized cats. Blood from the femoral artery was shunted through a pump to supply and control the entire portal blood flow. As shunted portal blood flow was varied over a wide range, the portal shunt resistance showed distensibility. Decreasing portal venous pressure from 15.0 +/- 0.9 to 11.1 +/- 0.6 mmHg (1 mmHg = 133.3 Pa) resulted in elevations of resistance of 58%. The relation between the resistance (R) and the distending pressure (Pd) was a constant, the index of contractility (IC), where IC = R.Pd3. In steady state, the IC was 485 +/- 55 mmHg4.mL-1.min.kg and did not change passively in response to changes in portal blood flow. In conclusion, portacaval shunts are passively distensible, and resistance is altered as a cubic function of the distending pressure. Because resistance is altered both actively and passively, the IC should prove useful to differentiate these alternatives for evaluation of changes in portal hypertensive therapy.

  2. The Effect of Ischemia and Reperfusion on Enteric Glial Cells and Contractile Activity in the Ileum.

    Science.gov (United States)

    Mendes, Cristina Eusébio; Palombit, Kelly; Vieira, Cátia; Silva, Isabel; Correia-de-Sá, Paulo; Castelucci, Patricia

    2015-09-01

    We investigated the effects of ischemia followed by different periods of reperfusion (I/R) on immunoreactive S100β-positive glial and Hu-immunoreactive neurons co-expressing the P2X2 receptor in the myenteric plexus of the rat ileum. The ileal artery was occluded for 35 min with an atraumatic vascular clamp. The animals were killed 24 h, 72 h, and 1 week after ischemia. Sham animals were not submitted to ileal artery occlusion. The relative density, size, and co-localization of P2X2 receptor-expressing cells in relation to S100β-immunoreactive glial and Hu-immunoreactive neuronal cells were evaluated. Additionally, we analyzed the effects of I/R on gastrointestinal transit and ileum contractile activity. The cellular density of P2X2 receptor and neuronal Hu immunoreactivity/cm(2) decreased after I/R, whereas glial S100β immunoreactivity/cm(2) increased. No significant differences between sham and I/R groups were observed regarding the perikarya area of Hu-positive neurons. The area of S100β-immunoreactive glial cells increased by 24.1 % 1 week after I/R compared with the 24 h group. Methylene blue progression along the small intestine decreased (P glial cells, may contribute to decreased GI motility after I/R.

  3. Cardiac index in atrio- and interventricular delay optimized cardiac resynchronization therapy and cardiac contractility modulation

    Directory of Open Access Journals (Sweden)

    Tumampos J.

    2015-09-01

    Full Text Available Cardiac resynchronization therapy (CRT is an established therapy for heart failure patients and improves quality of life in patients with sinus rhythm, reduced left ventricular ejection fraction (LVEF, left bundle branch block and wide QRS duration. Since approximately sixty percent of heart failure patients have a normal QRS duration they do not benefit or respond to the CRT. Cardiac contractility modulation (CCM releases nonexcitatoy impulses during the absolute refractory period in order to enhance the strength of the left ventricular contraction. The aim of the investigation was to evaluate differences in cardiac index between optimized and nonoptimized CRT and CCM devices versus standard values. Impedance cardiography, a noninvasive method was used to measure cardiac index (CI, a useful parameter which describes the blood volume during one minutes heart pumps related to the body surface. CRT patients indicate an increase of 39.74 percent and CCM patients an improvement of 21.89 percent more cardiac index with an optimized device.

  4. Accuracy of Dobutamine Stress Echocardiography in Detecting Recovery of Contractile Reserve after Revascularization of Ischemic Myocardium

    Directory of Open Access Journals (Sweden)

    Abas Ali karimi

    2007-09-01

    Full Text Available Background: This study was designed to investigate the accuracy of dobutamine stress echocardiography (DSE in detecting the post-revascularization recovery rate of contractile reserve (CR in ischemic myocardium. Methods: A total of 112 segments from seven patients with low ejection fraction (<35% and coronary artery disease were evaluated with DSE one week before and 12 weeks after coronary artery bypass graft surgery (CABG. Sensitivity, specificity, and positive and negative predictive values of DSE for detecting the recovery rate of CR were calculated based upon their standard definition and were presented with 95% confidence intervals (CI. Results: The mean baseline left ventricular ejection fraction was 31±4%, which reached 35±7% after CABG unremarkably. The recovery rates of resting function and CR were 18.2% and 50% for hypokinetic and 15.6% and 24.1 for akinetic segments respectively. Specificity, sensitivity, and positive and negative predictive values of DSE for detecting the recovery of CR were 83% (CI=69-97, 89% (CI=83-96, 94% (CI = 88-99, and 73 % (CI = 55-88, respectively. Conclusion: Despite acceptable sensitivity, specificity, and positive predictive value, DSE has a relatively lower negative predictive value for detecting the recovery of CR in ischemic myocardium and, consequently, the full extent of myocardial viability. Further sensitive techniques may, therefore, be needed to provide complementary information regarding long-term functional outcome.

  5. Contractile and relaxant actions of prostaglandins on guinea-pig isolated trachea.

    Science.gov (United States)

    Coleman, R. A.; Kennedy, I.

    1980-01-01

    1 The effects of 12 prostaglandins on guinea-pig isolated trachea have been examined in the presence of indomethacin. Two series of experiments were carried out, the first on preparations without tone ('zero tone'), and the second on preparations with tone induced with acetylcholine ('high tone'). 2 The compounds tested fell into two groups. The first, comprising prostaglandins F1 alpha, F2 alpha, F2 alpha acetal, I2 and Wy 17186, contracted both zero and high tone preparations. The second, comprising prostaglandins A1, A2, B1, B2, E1, E2 and F2 beta, contracted zero, but relaxed high tone preparations. Responses to the second group of compounds are probably the resultant of their contractile and relaxant actions. 3 The order of potency for contracting zero tone preparations was prostaglandin E (PGE) greater than F = 1 = Wy 17186 greater than B greater than A, 2-series compounds being 5 to 18 times more potent than 1-series compounds. 4 The order of potency for relaxing high tone preparations was PGE greater than F beta greater than B greater than A greater than Wy 17186 greater than F alpha = I = 0. There was little difference between the potency of 1- and 2-series compounds. 5 The possible relevance of these results to the interpretation of the effects of prostaglandins on human airways is discussed. PMID:7052343

  6. Cardiac contractile function during coronary stenosis in dogs: association of adenosine in glycolytic dependence.

    Science.gov (United States)

    Fang, H K; Sturgeon, C; Segil, L J; Ripper, R L; Law, W R

    1997-05-01

    We tested the hypothesis that during critical coronary stenosis, endogenous adenosine alters myocardial glucose utilization to support myocardial contractile function (MCF). Anesthetized mongrel dogs were instrumented to measure hemodynamic variables, regional MCF (sonomicrometry), and substrate uptakes. Critical coronary artery stenosis was established with a screw clamp on the left circumflex coronary artery (LCX). Either 8-phenyltheophylline (3 x 10(-7) mol/min; adenosine-receptor blockade), iodoacetate (1 x 10(-5) mol/min; glycolysis blockade), or vehicle was infused into the LCX and the left anterior descending coronary artery (LAD). Critical coronary stenosis caused small decreases in arterial blood pressure and LCX blood flow, but no significant changes in MCF or other hemodynamics. There was a significant decrease in the O2 supply-to-consumption ratio in the stenotic region and an increased glucose uptake. Infusion of either 8-phenyltheophylline or iodoacetate caused a decrease in MCF in the stenotic LCX region concomitant with a decreased glucose uptake and without further changes in blood flow. This was not seen in the nonstenotic (LAD) region. These data support the hypothesis, indicating that glycolysis is vital for maintaining regional MCF during a decrease in the myocardial O2 supply-to-consumption ratio and that adenosine is important in this regard, independent of its vasoactive properties.

  7. Overexpression of TEAD-1 in transgenic mouse striated muscles produces a slower skeletal muscle contractile phenotype.

    Science.gov (United States)

    Tsika, Richard W; Schramm, Christine; Simmer, Gretchen; Fitzsimons, Daniel P; Moss, Richard L; Ji, Juan

    2008-12-26

    TEA domain (TEAD) transcription factors serve important functional roles during embryonic development and in striated muscle gene expression. Our previous work has implicated a role for TEAD-1 in the fast-to-slow fiber-type transition in response to mechanical overload. To investigate whether TEAD-1 is a modulator of slow muscle gene expression in vivo, we developed transgenic mice expressing hemagglutinin (HA)-tagged TEAD-1 under the control of the muscle creatine kinase promoter. We show that striated muscle-restricted HA-TEAD-1 expression induced a transition toward a slow muscle contractile protein phenotype, slower shortening velocity (Vmax), and longer contraction and relaxation times in adult fast twitch extensor digitalis longus muscle. Notably, HA-TEAD-1 overexpression resulted in an unexpected activation of GSK-3alpha/beta and decreased nuclear beta-catenin and NFATc1/c3 protein. These effects could be reversed in vivo by mechanical overload, which decreased muscle creatine kinase-driven TEAD-1 transgene expression, and in cultured satellite cells by TEAD-1-specific small interfering RNA. These novel in vivo data support a role for TEAD-1 in modulating slow muscle gene expression.

  8. Human embryonic stem cell derived mesenchymal progenitors express cardiac markers but do not form contractile cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Christophe M Raynaud

    Full Text Available Mesenchymal progenitors or stromal cells have shown promise as a therapeutic strategy for a range of diseases including heart failure. In this context, we explored the growth and differentiation potential of mesenchymal progenitors (MPs derived in vitro from human embryonic stem cells (hESCs. Similar to MPs isolated from bone marrow, hESC derived MPs (hESC-MPs efficiently differentiated into archetypical mesenchymal derivatives such as chondrocytes and adipocytes. Upon treatment with 5-Azacytidine or TGF-β1, hESC-MPs modified their morphology and up-regulated expression of key cardiac transcription factors such as NKX2-5, MEF2C, HAND2 and MYOCD. Nevertheless, NKX2-5+ hESC-MP derivatives did not form contractile cardiomyocytes, raising questions concerning the suitability of these cells as a platform for cardiomyocyte replacement therapy. Gene profiling experiments revealed that, although hESC-MP derived cells expressed a suite of cardiac related genes, they lacked the complete repertoire of genes associated with bona fide cardiomyocytes. Our results suggest that whilst agents such as TGF-β1 and 5-Azacytidine can induce expression of cardiac related genes, but treated cells retain a mesenchymal like phenotype.

  9. Spontaneous Regression of Lumbar Herniated Disc

    Directory of Open Access Journals (Sweden)

    Chun-Wei Chang

    2009-12-01

    Full Text Available Intervertebral disc herniation of the lumbar spine is a common disease presenting with low back pain and involving nerve root radiculopathy. Some neurological symptoms in the majority of patients frequently improve after a period of conservative treatment. This has been regarded as the result of a decrease of pressure exerted from the herniated disc on neighboring neurostructures and a gradual regression of inflammation. Recently, with advances in magnetic resonance imaging, many reports have demonstrated that the herniated disc has the potential for spontaneous regression. Regression coincided with the improvement of associated symptoms. However, the exact regression mechanism remains unclear. Here, we present 2 cases of lumbar intervertebral disc herniation with spontaneous regression. We review the literature and discuss the possible mechanisms, the precipitating factors of spontaneous disc regression and the proper timing of surgical intervention.

  10. Spontaneous hemothorax: primary pleural epithelioid angiosarcoma

    Directory of Open Access Journals (Sweden)

    Amit Panjwani

    2016-01-01

    Full Text Available Spontaneous hemothorax is a rare condition seen in coagulation and vascular disorders. Uncommonly, malignant neoplasms may cause spontaneous hemothorax. Primary pleural epithelioid angiosarcomas (excluding the cases with pleuropulmonary or chest wall involvement are extremely rare pleural tumors, which may be mistaken for mesothelioma or adenocarcinoma, and only 19 cases (one of them from India have been reported in the English literature, to date. It commonly occurs in older men, has a nonspecific clinicoradiological presentation, and carries a poor prognosis with no survivors beyond a year of establishing the diagnosis. We report a case of primary pleural epithelioid angiosarcoma presenting as a life-threatening spontaneous hemothorax. We also present a brief literature review on pleural angiosarcoma.

  11. Computed tomographic findings of spontaneous intracranial hemorrhage

    Energy Technology Data Exchange (ETDEWEB)

    Ko, Seung Sook; Kim, Young Sook; Kim, Young Chul [College of Medicine, Chosun University, Kwangju (Korea, Republic of)

    1987-10-15

    Computed tomography (CT) was a reliable technique to evaluate the exact size and location of spontaneous intracranial hemorrhage and to predict it's prognosis. Fifty-nine cases of spontaneous intracranial hemorrhage were evaluated and reviewed by CT scan. The following results were obtained. 1. The sex ratio of male to female was 1 to 1.4, The highest incidence was in 6th and 7th decades. 2. The most common cause of spontaneous intracranial hemorrhage was hypertension (74.6%), followed by the aneurysm (13.5%), arteriovenous malformation (5.1%), occlusive vascular disease (3.4%), and blood dyscrasia (3.4%). 3. The most common location was basal ganglia and thalamic hemorrhage (37.3%), followed by lobar hemorrhage (27.1%), cerebellar hemorrhage (13.5%), and subarachnoid hemorrhage (11.9%). 4. Primary intraventricular hemorrhage carried the highest mortality. 5. The larger volume of hematoma, the higher the mortality rate.

  12. Spontaneous Perforation of Pyometra: A Case Report

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available Pyometra is the accumulation of purulent material in the uterine cavity. Its reported incidence is 0.01–0.5% in gynecologic patients; however, as far as elderly patients are concerned, its incidence is 13.6% [3]. The most common cause of pyometra is malignant diseases of genital tract and the consequences of their treatment (radiotherapy. Other causes are benign tumors like leiomyoma, endometrial polyps, senile cervicitis, cervical occlusion after surgery, puerperal infections, and congenital cervical anomalies. Spontaneous rupture of the uterus is an extremely rare complication of pyometra. To our knowledge, only 21 cases of spontaneous perforation of pyometra have been reported in English literature since 1980. This paper reports an additional case of spontaneous uterine rupture.

  13. The neuromechanical functional contractile properties of the thigh muscles measured using tensiomyography in male athletes and non-athletes

    Directory of Open Access Journals (Sweden)

    Toskić Lazar

    2016-01-01

    Full Text Available Involuntary neuromechanical muscle contractile properties, especially of the extensor muscles and knee joint flexors as the largest muscle groups of the caudal part of the body, play an important role in both everyday movement and sport. Based on these data we can obtain important information on the functional properties of muscles. The basic means of evaluation of the functional involuntary neuromechanical muscles contractile properties is the non-invasive tensiomyographic method (TMG. The aim of this study was to determine the differences between the involuntary neuromechanical contractile properties of the thigh muscles measured using the TMG method on a sample of male athletes and non-athletes. The sample of participants was made up of 17 athletes and 10 non-athletes. By applying the multivariate analysis of variance (MANOVA and the t-test, we achieved results which indicate that of the overall 30 variables, a difference was determined among 13 of them. Most of the differences were determined for the extensor muscles of the right knee, especially of the rectus femoris muscle. It was also shown that in addition to the main knee joint extensor muscle (rectus femoris the main knee joint flexor muscle (biceps femoris also takes part in the definition of the difference between athletes and non-athletes. The results have shown that the following variables: contraction time (Tc and delay contraction time (Td are the functional parameters for which the highest difference between athletes and non-athletes were determined (from t = -2.284, p < 0.05 for the vastus lateralis of the right leg to t = -4.018, p < 0.01 for the rectus femoris of the left leg. These results have shown that it is possible to determine the differences in the functional involuntary neuromechanical contractile properties of the thigh muscles among trained and untrained individuals using the tensiomyographic method, but at the same time indicated that these differences were very

  14. Stochastic Ratcheting on a Funneled Energy Landscape Is Necessary for Highly Efficient Contractility of Actomyosin Force Dipoles

    Science.gov (United States)

    Komianos, James E.; Papoian, Garegin A.

    2018-04-01

    Current understanding of how contractility emerges in disordered actomyosin networks of nonmuscle cells is still largely based on the intuition derived from earlier works on muscle contractility. In addition, in disordered networks, passive cross-linkers have been hypothesized to percolate force chains in the network, hence, establishing large-scale connectivity between local contractile clusters. This view, however, largely overlooks the free energy of cross-linker binding at the microscale, which, even in the absence of active fluctuations, provides a thermodynamic drive towards highly overlapping filamentous states. In this work, we use stochastic simulations and mean-field theory to shed light on the dynamics of a single actomyosin force dipole—a pair of antiparallel actin filaments interacting with active myosin II motors and passive cross-linkers. We first show that while passive cross-linking without motor activity can produce significant contraction between a pair of actin filaments, driven by thermodynamic favorability of cross-linker binding, a sharp onset of kinetic arrest exists at large cross-link binding energies, greatly diminishing the effectiveness of this contractility mechanism. Then, when considering an active force dipole containing nonmuscle myosin II, we find that cross-linkers can also serve as a structural ratchet when the motor dissociates stochastically from the actin filaments, resulting in significant force amplification when both molecules are present. Our results provide predictions of how actomyosin force dipoles behave at the molecular level with respect to filament boundary conditions, passive cross-linking, and motor activity, which can explicitly be tested using an optical trapping experiment.

  15. Cardiac-specific catalase overexpression rescues anthrax lethal toxin-induced cardiac contractile dysfunction: role of oxidative stress and autophagy

    OpenAIRE

    Kandadi, Machender R; Yu, Xuejun; Frankel, Arthur E; Ren, Jun

    2012-01-01

    Abstract Background Lethal and edema toxins secreted by Bacillus anthracis during anthrax infection were found to incite serious cardiovascular complications. However, the underlying mechanisms in anthrax lethal toxin-induced cardiac anomalies remain unknown. This study was designed to evaluate the impact of antioxidant enzyme catalase in anthrax lethal toxin-induced cardiomyocyte contractile dysfunction. Methods Wild type (WT) and cardiac-specific catalase overexpression mice were challenged...

  16. Dynamic dyssynchrony and impaired contractile reserve of the left ventricle in beta-thalassaemia major: an exercise echocardiographic study.

    Directory of Open Access Journals (Sweden)

    Yiu-fai Cheung

    Full Text Available BACKGROUND: Performance of the left ventricle during exercise stress in thalassaemia patients is uncertain. We aimed to explore the phenomenon of dynamic dyssynchrony and assess contractile reserve in patients with beta-thalassaemia major and determine their relationships with myocardial iron load. METHODS AND RESULTS: Thirty-two thalassaemia patients (16 males, aged 26.8 ± 6.9 years, without heart failure and 17 healthy controls were studied. Their left ventricular (LV volumes, ejection fraction, systolic dyssynchrony index (SDI, and myocardial acceleration during isovolumic LV contraction (IVA were determined at rest and during submaximal bicycle exercise testing using 3-dimensional and tissue Doppler echocardiography. Myocardial iron load as assessed by T2* cardiac magnetic resonance in patients were further related to indices of LV dyssynchrony and contractile reserve. At rest, patients had significantly greater LV SDI (p4.6%, control+2SD increased from baseline 25% to 84% in patients. Δ SDI(exercise-baseline correlated with exercise-baseline differences in LV ejection fraction (p<0.001 and stroke volume (p = 0.006. Compared with controls, patients had significantly less exercise-induced increase in LV ejection fraction, cardiac index, and IVA (interaction, all p<0.05 and had impaired contractile reserve as reflected by the gentler IVA-heart rate slope (p = 0.018. Cardiac T2* in patients correlated with baseline LV SDI (r = -0.44, p = 0.011 and IVA-heart rate slope (r = 0.36, p = 0.044. CONCLUSIONS: Resting LV dyssynchrony is associated with myocardial iron load. Exercise stress further unveils LV dynamic dyssynchrony and impaired contractile reserve in patients with beta-thalassaemia major.

  17. Differential Kolaviron Attenuated Contractile Responses to Agonists on Isolated Rabbit Aorta in Na+-K+ Pump Blockade.

    Science.gov (United States)

    Uche, O K; Ofeimun, J O

    2017-12-30

    The mechanism of kolaviron-induced vascular smooth muscles (VSMs) responses has not been fullycharacterised. The present study investigated the effect and mode of action of kolaviron a biflavanoid-complex and majorcomponent of Garcinia Kola-fraction on differential contractile responses to agonists-[phenylephrine (PHE) and histamine(HIST)] on VSMs of rabbit isolated aortic rings in K+-free physiological salt solution (KFPSS). Cumulative concentrationresponses to PHE and HIST were examined on 2 mm ring segments of the thoracic aortae which were suspended in 20 mlorgan baths containing physiological salt solution (PSS) for measurement of isometric contractions, at 370C and pH 7.4. Themedium was bubbled with 95% O2, 5% CO2, and rings were given an initial load of 1g. Cumulative contractile responses tothe agonists were studied in normal PSS (control) and following 30 minutes exposure to K+-free PSS and/or 800µg/mLkolaviron. Contractile responses were expressed as percentage of 80 mM K+ contractions in normal PSS. Maximalcontractions (Emax) induced by PHE and HIST compared with high K+ contraction in the various preparations weredifferentially altered following exposure to K+-free or 800µg/mL kolaviron in both intact (+E) and endotheliumdenuded (-E) rings. Based on the efficacy (Emax) and potency (EC50) values for the dose-response curves of the agonists, it isconcluded that enhanced differential contractile responses elicited by agonists in K+-free PSS were significantly attenuatedby kolaviron concentration-dependently. This observation probably suggests the existence of another pathway of kolavironmode of action in vascular smooth muscle reactivity.

  18. Stochastic Ratcheting on a Funneled Energy Landscape Is Necessary for Highly Efficient Contractility of Actomyosin Force Dipoles

    Directory of Open Access Journals (Sweden)

    James E. Komianos

    2018-04-01

    Full Text Available Current understanding of how contractility emerges in disordered actomyosin networks of nonmuscle cells is still largely based on the intuition derived from earlier works on muscle contractility. In addition, in disordered networks, passive cross-linkers have been hypothesized to percolate force chains in the network, hence, establishing large-scale connectivity between local contractile clusters. This view, however, largely overlooks the free energy of cross-linker binding at the microscale, which, even in the absence of active fluctuations, provides a thermodynamic drive towards highly overlapping filamentous states. In this work, we use stochastic simulations and mean-field theory to shed light on the dynamics of a single actomyosin force dipole—a pair of antiparallel actin filaments interacting with active myosin II motors and passive cross-linkers. We first show that while passive cross-linking without motor activity can produce significant contraction between a pair of actin filaments, driven by thermodynamic favorability of cross-linker binding, a sharp onset of kinetic arrest exists at large cross-link binding energies, greatly diminishing the effectiveness of this contractility mechanism. Then, when considering an active force dipole containing nonmuscle myosin II, we find that cross-linkers can also serve as a structural ratchet when the motor dissociates stochastically from the actin filaments, resulting in significant force amplification when both molecules are present. Our results provide predictions of how actomyosin force dipoles behave at the molecular level with respect to filament boundary conditions, passive cross-linking, and motor activity, which can explicitly be tested using an optical trapping experiment.

  19. Age-dependent changes in contractile function and passive elastic properties of myocardium from mice lacking muscle LIM protein (MLP).

    Science.gov (United States)

    Unsöld, Bernhard; Schotola, Hanna; Jacobshagen, Claudius; Seidler, Tim; Sossalla, Samuel; Emons, Julius; Klede, Stefanie; Knöll, Ralph; Guan, Kaomei; El-Armouche, Ali; Linke, Wolfgang A; Kögler, Harald; Hasenfuss, Gerd

    2012-04-01

    Muscle LIM protein (MLP) null mice are often used as a model for human dilated cardiomyopathy. So far, little is known about the time course and pathomechanisms leading to the development of the adult phenotype. We systematically analysed the contractile phenotype, myofilament calcium (Ca(2)(+)) responsiveness, passive myocardial mechanics, histology, and mRNA expression in mice aged 4 and 12 weeks. In 4-week-old animals, there was no significant difference in the force-frequency relationship (FFR) and catecholamine response of intact isolated papillary muscles between wild-type (WT) and MLP null myocardium. In 12-week-old animals, WT myocardium exhibited a significantly positive FFR, while that of MLP null mice was significantly negative, and the inotropic response to catecholamines was significantly reduced in MLP null mice. This time course of decline in contractile function was confirmed in vivo by echocardiography. Whereas at 4 weeks of age MLP null mice and WT littermates showed similar levels of SERCA2a (sarcoplasmic reticulum Ca(2+) ATPase) expression, the expression was significantly lower in 12-week-old MLP null mice compared with littermate controls. Myofilament Ca(2)(+) responsiveness was not affected by the lack of MLP, irrespective of age. Whereas in 4-week-old animals MLP null myocardium showed a trend to an increased compliance compared with the WT, myocardium of 12-week-old MLP null mice was significantly less compliant than WT myocardium. Parallel to the decrease in compliance there was an increase in fibrosis in the MLP null animals. Our data suggest that MLP deficiency does not primarily influence myocardial contractility. A lack of MLP leads to an age-dependent impairment of excitation-contraction coupling with resulting contractile dysfunction and secondary fibrosis.

  20. Pharmacological evidence of hypotensive activity of Marrubium vulgare and Foeniculum vulgare in spontaneously hypertensive rat.

    Science.gov (United States)

    El Bardai, S; Lyoussi, B; Wibo, M; Morel, N

    2001-05-01

    The hypotensive effects of the water extract of Marrubium vulgare L. and Foeniculum vulgare L. were investigated in spontaneously hypertensive rats (SHR) and in normotensive Wistar-Kyoto rats (WKY). Oral administration of Marrubium or Foeniculum extract lowered the systolic blood pressure of SHR but not of WKY. In SHR, Foeniculum but not Marrubium treatment increased water, sodium and potassium excretion. Ex vivo as well as in vitro, Marrubium extract inhibited the contractile responses of rat aorta to noradrenaline and to KCl (100 mM). Inhibition was greater in aorta from SHR compared to WKY and was not affected by the NO synthase inhibitor N-nitro-L-arginine. Vascular effects of Foeniculum extract were less pronounced than those of Marrubium and were blocked by N-nitro-L-arginine. These results indicate that hypotensive activity of Marrubium and Foeniculum extracts seems to be mediated through different pathways: Foeniculum appeared to act mainly as a diuretic and a natriuretic while Marrubium displayed vascular relaxant activity.

  1. Towards a Tissue-Engineered Contractile Fontan-Conduit: The Fate of Cardiac Myocytes in the Subpulmonary Circulation.

    Directory of Open Access Journals (Sweden)

    Daniel Biermann

    Full Text Available The long-term outcome of patients with single ventricles improved over time, but remains poor compared to other congenital heart lesions with biventricular circulation. Main cause for this unfavourable outcome is the unphysiological hemodynamic of the Fontan circulation, such as subnormal systemic cardiac output and increased systemic-venous pressure. To overcome this limitation, we are developing the concept of a contractile extracardiac Fontan-tunnel. In this study, we evaluated the survival and structural development of a tissue-engineered conduit under in vivo conditions. Engineered heart tissue was generated from ventricular heart cells of neonatal Wistar rats, fibrinogen and thrombin. Engineered heart tissues started beating around day 8 in vitro and remained contractile in vivo throughout the experiment. After culture for 14 days constructs were implanted around the right superior vena cava of Wistar rats (n = 12. Animals were euthanized after 7, 14, 28 and 56 days postoperatively. Hematoxylin and eosin staining showed cardiomyocytes arranged in thick bundles within the engineered heart tissue-conduit. Immunostaining of sarcomeric actin, alpha-actin and connexin 43 revealed a well -developed cardiac myocyte structure. Magnetic resonance imaging (d14, n = 3 revealed no constriction or stenosis of the superior vena cava by the constructs. Engineered heart tissues survive and contract for extended periods after implantation around the superior vena cava of rats. Generation of larger constructs is warranted to evaluate functional benefits of a contractile Fontan-conduit.

  2. Contractile Defect Caused by Mutation in MYBPC3 Revealed under Conditions Optimized for Human PSC-Cardiomyocyte Function

    Directory of Open Access Journals (Sweden)

    Matthew J. Birket

    2015-10-01

    Full Text Available Maximizing baseline function of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs is essential for their effective application in models of cardiac toxicity and disease. Here, we aimed to identify factors that would promote an adequate level of function to permit robust single-cell contractility measurements in a human induced pluripotent stem cell (hiPSC model of hypertrophic cardiomyopathy (HCM. A simple screen revealed the collaborative effects of thyroid hormone, IGF-1 and the glucocorticoid analog dexamethasone on the electrophysiology, bioenergetics, and contractile force generation of hPSC-CMs. In this optimized condition, hiPSC-CMs with mutations in MYBPC3, a gene encoding myosin-binding protein C, which, when mutated, causes HCM, showed significantly lower contractile force generation than controls. This was recapitulated by direct knockdown of MYBPC3 in control hPSC-CMs, supporting a mechanism of haploinsufficiency. Modeling this disease in vitro using human cells is an important step toward identifying therapeutic interventions for HCM.

  3. Generation of Functional Cardiomyocytes from Efficiently Generated Human iPSCs and a Novel Method of Measuring Contractility.

    Directory of Open Access Journals (Sweden)

    Sheeja Rajasingh

    Full Text Available Human induced pluripotent stem cells (iPSCs derived cardiomyocytes (iCMCs would provide an unlimited cell source for regenerative medicine and drug discoveries. The objective of our study is to generate functional cardiomyocytes from human iPSCs and to develop a novel method of measuring contractility of CMCs. In a series of experiments, adult human skin fibroblasts (HSF and human umbilical vein endothelial cells (HUVECs were treated with a combination of pluripotent gene DNA and mRNA under specific conditions. The iPSC colonies were identified and differentiated into various cell lineages, including CMCs. The contractile activity of CMCs was measured by a novel method of frame-by-frame cross correlation (particle image velocimetry-PIV analysis. Our treatment regimen transformed 4% of HSFs into iPSC colonies at passage 0, a significantly improved efficiency compared with use of either DNA or mRNA alone. The iPSCs were capable of differentiating both in vitro and in vivo into endodermal, ectodermal and mesodermal cells, including CMCs with >88% of cells being positive for troponin T (CTT and Gata4 by flow cytometry. We report a highly efficient combination of DNA and mRNA to generate iPSCs and functional iCMCs from adult human cells. We also report a novel approach to measure contractility of iCMCs.

  4. Generation of Functional Cardiomyocytes from Efficiently Generated Human iPSCs and a Novel Method of Measuring Contractility.

    Science.gov (United States)

    Rajasingh, Sheeja; Thangavel, Jayakumar; Czirok, Andras; Samanta, Saheli; Roby, Katherine F; Dawn, Buddhadeb; Rajasingh, Johnson

    2015-01-01

    Human induced pluripotent stem cells (iPSCs) derived cardiomyocytes (iCMCs) would provide an unlimited cell source for regenerative medicine and drug discoveries. The objective of our study is to generate functional cardiomyocytes from human iPSCs and to develop a novel method of measuring contractility of CMCs. In a series of experiments, adult human skin fibroblasts (HSF) and human umbilical vein endothelial cells (HUVECs) were treated with a combination of pluripotent gene DNA and mRNA under specific conditions. The iPSC colonies were identified and differentiated into various cell lineages, including CMCs. The contractile activity of CMCs was measured by a novel method of frame-by-frame cross correlation (particle image velocimetry-PIV) analysis. Our treatment regimen transformed 4% of HSFs into iPSC colonies at passage 0, a significantly improved efficiency compared with use of either DNA or mRNA alone. The iPSCs were capable of differentiating both in vitro and in vivo into endodermal, ectodermal and mesodermal cells, including CMCs with >88% of cells being positive for troponin T (CTT) and Gata4 by flow cytometry. We report a highly efficient combination of DNA and mRNA to generate iPSCs and functional iCMCs from adult human cells. We also report a novel approach to measure contractility of iCMCs.

  5. A casein kinase 1 prevents expulsion of the oocyte meiotic spindle into a polar body by regulating cortical contractility

    Science.gov (United States)

    Flynn, Jonathan R.; McNally, Francis J.

    2017-01-01

    During female meiosis, haploid eggs are generated from diploid oocytes. This reduction in chromosome number occurs through two highly asymmetric cell divisions, resulting in one large egg and two small polar bodies. Unlike mitosis, where an actomyosin contractile ring forms between the sets of segregating chromosomes, the meiotic contractile ring forms on the cortex adjacent to one spindle pole, then ingresses down the length of the spindle to position itself at the exact midpoint between the two sets of segregating chromosomes. Depletion of casein kinase 1 gamma (CSNK-1) in Caenorhabditis elegans led to the formation of large polar bodies that contain all maternal DNA, because the contractile ring ingressed past the spindle midpoint. Depletion of CSNK-1 also resulted in the formation of deep membrane invaginations during meiosis, suggesting an effect on cortical myosin. Both myosin and anillin assemble into dynamic rho-dependent cortical patches that rapidly disassemble in wild-type embryos. CSNK-1 was required for disassembly of both myosin patches and anillin patches. Disassembly of anillin patches was myosin independent, suggesting that CSNK-1 prevents expulsion of the entire meiotic spindle into a polar body by negatively regulating the rho pathway rather than through direct inhibition of myosin. PMID:28701347

  6. On spontaneous breakdown in Σ-models

    International Nuclear Information System (INIS)

    Ivanov, E.A.

    1975-01-01

    The group theory aspects of spontaneous breakdown in linear Σ-models are discussed. General conditions are formulated under which multiplet of group G (compact or noncompact) is suitable for constructing the Σ-model with a given subgroup of stability of vacuum. It is shown that the Σ-models of spontaneously broken space-time symmetries can be constructed in general only if some extra coordinates are introduced in addition to an ordinary 4-coordinate xsub(μ). The connection between Σ-models of internal symmetries and appropriate nonlinear realizations has also been investigated

  7. Two cases of spontaneous temporal encephalocele.

    Science.gov (United States)

    Kamiya, Kouhei; Mori, Harushi; Kunimatsu, Akira; Kawai, Kensuke; Usami, Kenichi; Ohtomo, Kuni

    2012-12-01

    This is a report of two cases of spontaneous temporal encephalocele: one was anteroinferior and presented with epilepsy; the other was posteroinferior and presented with facial neuritis and labyrinthitis. Spontaneous temporal encephalocele is relatively rare and apparently not familiar to a majority of primary physicians. It may present with a variety of symptoms according to its anatomical location, including cerebrospinal fluid fistulas, recurrent meningitis, chronic otitis media, hearing loss, facial nerve palsy and medically intractable epilepsy. Attention should be paid to this disease entity, as it is easily overlooked in imaging studies and can leave serious neurological deficits. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  8. Spontaneous abortion and physical strain around implantation

    DEFF Research Database (Denmark)

    Hjollund, N H; Jensen, Tina Kold; Bonde, Jens Peter

    2000-01-01

    Existing studies of physical strain and spontaneous abortion are mainly retrospective or based only on pregnancies that have survived the first trimester. Furthermore, almost all studies have relied on averaged measures of physical strain, which tend to blur an effect if peak values during short...... pregnancy the women recorded physical strain prospectively in a structured diary. Physical strain around the time of implantation was associated with later spontaneous abortion. The adjusted risk ratio for women who reported physical strain higher than average at day 6 to 9 after the estimated date...

  9. Need for spontaneous breakdown of chiral symmetry

    International Nuclear Information System (INIS)

    Salomone, A.; Schechter, J.; Tudron, T.

    1981-01-01

    The question of whether the chiral symmetry of the theory of strong interactions (with massless quarks) is required to be spontaneously broken is examined in the framework of a previously discussed effective Lagrangian for quantum chromodynamics. The assumption that physical masses of the theory be finite leads in a very direct way to the necessity of spontaneous breakdown. This result holds for all N/sub F/> or =2, where N/sub F/ is the number of different flavors of light quarks. The atypical cases N/sub F/ = 1,2 are discussed separately

  10. Spontaneous subdural hematoma associated to Duret hemorrhage

    Directory of Open Access Journals (Sweden)

    William Alves Martins, MD

    2015-03-01

    Full Text Available Subdural hematoma (SH is a neurosurgical emergency, usually caused by head trauma. Non-traumatic causes include aneurysm or arterial–venous malformation rupture, coagulopathy and others. We report the case of a 66 year-old man who developed apparently unprovoked signs of increased intracranial pressure. Brain computed tomography scan showed an acute spontaneous SH, surgically treated. Throughout surgery, a ruptured cortical artery with intensive bleeding appeared and was cauterized. After surgery, patient remained comatose and a new CT demonstrated Duret hemorrhage at the brainstem. Acute spontaneous SH of arterial origin is rare and highly lethal, in which a good prognosis relies on early diagnosis and treatment.

  11. Primer on spontaneous heating and pyrophoricity

    Energy Technology Data Exchange (ETDEWEB)

    1994-12-01

    This primer was prepared as an information resource for personnel responsible for operation of DOE nuclear facilities. It has sections on combustion principles, spontaneous heating/ignition of hydrocarbons and organics, pyrophoric gases and liquids, pyrophoric nonmetallic solids, pyrophoric metals (including Pu and U), and accident case studies. Although the information in this primer is not all-encompassing, it should provide the reader with a fundamental knowledge level sufficient to recognize most spontaneous combustion hazards and how to prevent ignition and widespread fires. This primer is provided as an information resource only, and is not intended to replace any fire protection or hazardous material training.

  12. Cavity enhanced rephased amplified spontaneous emission

    International Nuclear Information System (INIS)

    A Williamson, Lewis; J Longdell, Jevon

    2014-01-01

    Amplified spontaneous emission is usually treated as an incoherent noise process. Recent theoretical and experimental work using rephasing optical pulses has shown that rephased amplified spontaneous emission (RASE) is a potential source of wide bandwidth time-delayed entanglement. Due to poor echo efficiency the plain RASE protocol does not in theory achieve perfect entanglement. Experiments done to date show a very small amount of entanglement at best. Here we show that RASE can, in principle, produce perfect multimode time-delayed two mode squeezing when the active medium is placed inside a Q-switched cavity. (paper)

  13. Spontaneous supersymmetry breaking on the lattice

    Energy Technology Data Exchange (ETDEWEB)

    Wenger, Urs [Albert Einstein Center for Fundamental Physics, Institute for Theoretical Physics, University of Bern, Sidlerstrasse 5, CH-3012 Bern (Switzerland)

    2013-07-01

    We discuss various strategies for regularising supersymmetric quantum field theories on a space-time lattice. In general, simulations of lattice models with spontaneously broken supersymmetry suffer from a fermion sign problem related to the vanishing of the Witten index. We discuss a novel approach which evades this problem in low dimensions by formulating the path integral on the lattice in terms of fermion loops. Then we present exact results on the spectrum and the Witten index for N=2 supersymmetric quantum mechanics and results from simulations of the spontaneously broken N=1 Wess-Zumino model.

  14. Inhibition of porcine detrusor contractility by the flavonoid fraction of Bryophyllum pinnatum--a potential phytotherapeutic drug for the treatment of the overactive bladder syndrome.

    Science.gov (United States)

    Fürer, K; Eberli, D; Betschart, C; Brenneisen, R; De Mieri, M; Hamburger, M; Mennet-von Eiff, M; Potterat, O; Schnelle, M; Simões-Wüst, A P; von Mandach, U

    2015-01-15

    To determine if the phytotherapeutic agent, Bryophyllum pinnatum, could serve as an alternative drug for the overactive bladder syndrome, and to characterise the fraction responsible for the inhibition of detrusor contractility. Fractions were prepared from the MeOH extract of B. pinnatum and further analysed by HPLC-PDA-MS. Detrusor muscle strips were prepared from porcine bladders and the electrically induced muscle contractility measured by organ bath. The effect of B. pinnatum leaf press juice (2.5-10%), a flavonoid fraction (0.1-1 mg/ml), and a bufadienolide fraction (0.1-40 μg/ml) on detrusor contractility was assessed and compared with controls (polar fraction (0.5-5 mg/ml) and oxybutynin (10(-8)-10(-6) M)). The press juice, at a concentration of 10% led to a reduction of detrusor contractility. Bladder strips treated with the flavonoid fraction showed a significant reduction of the contractility to 21.3 ± 5.2% (1 mg/ml) while the bufadienolide fraction had no inhibitory effect in the investigated concentrations. The polar fraction showed a reduction of the contractility in a pH-dependent fashion. At 10(-6) M concentration oxybutynin reduced the detrusor contractility to 21.9 ± 4.7%. The flavonoid fraction of Bryophyllum pinnatum reduces the porcine detrusor contractility in a dose- and time-dependent manner. Fractions from B. pinnatum may be a new pharmacological approach for the treatment of OAB. Copyright © 2014. Published by Elsevier GmbH.

  15. Ca(2+) -calmodulin interacts with DdCAD-1 and promotes DdCAD-1 transport by contractile vacuoles in Dictyostelium cells.

    Science.gov (United States)

    Sriskanthadevan, Shrivani; Brar, Simuran K; Manoharan, Kumararaaj; Siu, Chi-Hung

    2013-04-01

    The Ca(2+) -dependent cell-cell adhesion molecule DdCAD-1, encoded by the cadA gene of Dictyostelium discoideum, is synthesized at the onset of development as a soluble protein and then transported to the plasma membrane by contractile vacuoles. Calmodulin associates with contractile vacuoles in a Ca(2+) -dependent manner, and co-localizes with DdCAD-1 on the surface of contractile vacuoles. Bioinformatics analysis revealed multiple calmodulin-binding motifs in DdCAD-1. Co-immunoprecipitation and pull-down studies showed that only Ca(2+) -bound calmodulin was able to bind DdCAD-1. Structural integrity of DdCAD-1, but not the native conformation, was required for its interaction with calmodulin. To investigate the role of calmodulin in the import of DdCAD-1 into contractile vacuoles, an in vitro import assay consisting of contractile vacuoles derived from cadA(-) cells and recombinant proteins was employed. Prior stripping of the bound calmodulin from contractile vacuoles by EGTA impaired import of DdCAD-1, which was restored by addition of exogenous calmodulin. The calmodulin antagonists W-7 and compound 48/80 blocked the binding of calmodulin onto stripped contractile vacuoles, and inhibited the import of DdCAD-1. Together, the data show that calmodulin forms a complex with DdCAD-1 and promotes the docking and import of DdCAD-1 into contractile vacuoles. CaM physically interacts with DdCAD-1 by pull down (View Interaction: 1, 2) DdCAD-1 binds to CaM by far western blotting (View interaction) DdCAD-1 physically interacts with CaM by anti bait coimmunoprecipitation (View interaction). © 2013 The Authors Journal compilation © 2013 FEBS.

  16. Regulation of glycogen synthesis in rat skeletal muscle after glycogen-depleting contractile activity: effects of adrenaline on glycogen synthesis and activation of glycogen synthase and glycogen phosphorylase.

    OpenAIRE

    Franch, J; Aslesen, R; Jensen, J

    1999-01-01

    We investigated the effects of insulin and adrenaline on the rate of glycogen synthesis in skeletal muscles after electrical stimulation in vitro. The contractile activity decreased the glycogen concentration by 62%. After contractile activity, the glycogen stores were fully replenished at a constant and high rate for 3 h when 10 m-i.u./ml insulin was present. In the absence of insulin, only 65% of the initial glycogen stores was replenished. Adrenaline decreased insulin-stimulated glycogen s...

  17. Functional involvement of protein kinase C, Rho-kinase and TRPC3 decreases while PLC increases with advancement of pregnancy in mediating oxytocin-induced myometrial contractions in water buffaloes (Bubalus bubalis).

    Science.gov (United States)

    Sharma, Abhishek; Nakade, Udayraj P; Choudhury, Soumen; Garg, Satish Kumar

    2017-04-01

    Present study unravels the involvement of different calcium signaling pathways in oxytocin-induced contractions in myometrium of non-pregnant and pregnant buffaloes during early and mid-pregnancy stages. Uteri of pregnant animals were more sensitive than of non-pregnant buffaloes. Phasic contractions and frequency of contraction significantly increased with advancement of pregnancy, while tonic contractions non-significantly and amplitude significantly decreased from six months pregnancy onward. Oxytocin produced concentration-dependent-contraction on isolated myometrial strips of pregnant and non-pregnant buffaloes and the dose response curves (DRCs) of oxytocin were significantly (P < 0.05) shifted to right in the presence of nifedipine (1 μM), in Ca 2+ -free Ringer Locke solution (RLS), ruthenium red (30 μM), ruthenium red + nifedipine, cyclopiazonic acid (CPA; Ca 2+ free RLS as well as RLS), CPA (10 μM)+nifedipine, U-73122 (1 μM) + nifedipine and SKF96365 (25 μM) on uteri of non-pregnant and pregnant (early and mid) animals. The DRCs were also significantly shifted towards right in the presence of Y-27632 (10 μM), GF109203X (5 μM) and Pyr3 (10 μM) on uteri of non-pregnant and early pregnancy stage buffaloes while only in the presence of U-73122 (1 μM) on uteri of mid-pregnancy stage buffaloes. Our finding suggest that and L-type Ca 2+ channels, IP3-RyR-gated, and store-operated calcium channels including transient receptor potential channel (TRPC) pathways play significant role in mediating oxytocin-induced contractions in myometrium of pregnant and non-pregnant buffaloes. SERCA plays major role only during early-pregnancy while functional role of protein kinase C (PKC), Rho-kinase and TRPC3 pathways decreased and role of G-protein coupled receptor-phospholipase C (GPCR-PLC) pathway increased with advancement of pregnancy. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Wheaten ferments spontaneous fermantation in biotechnological methods

    OpenAIRE

    KAKHRAMON SANOQULOVICH RAKHMONOV; ISABAEV ISMAIL BABADJANOVICH

    2016-01-01

    In article are shown results of research of biotechnological properties of wheaten leavens of spontaneous fermentation (in the example of pea-anisetree leaven) and their analysis. Also is established influence of the given type of leavens on the basic biopolymers of the flour, on the property of the pastry and quality of bread from wheaten flour.

  19. Original article Spontaneous Pregnancy Outcome after Surgical ...

    African Journals Online (AJOL)

    2011-09-28

    Sep 28, 2011 ... Table 2: Spontaneous pregnancy in relation to postoperative semen parameters. (no statistically significant difference), comparable to the mean ages of 22, 28.4 and. 34.9 years, respectively, reported by Bach et al9, Abdel- Meguid et al10 and Baazeem et al11. The mean age of the wives who did or did.

  20. Spontaneous symmetry breakdown in gauge theories

    International Nuclear Information System (INIS)

    Scadron, M.D.

    1982-01-01

    The dynamical theory of spontaneous breakdown correctly predicts the bound states and relates the order parameters of electron-photon superconductivity and quark-gluon chiral symmetry. A similar statement cannot be made for the standard electro-weak gauge symmetry. (author)

  1. Identical Twin Primigravid Sisters -Spontaneous Labour and ...

    African Journals Online (AJOL)

    We report 2 cases of identical twin sisters, the older sibling getting married 14 months earlier but both got pregnant for their first child at about the same time and were managed by the same Obstetrician and fell into spontaneous labour within a few hours of each other. Both were delivered by emergency caesarean section ...

  2. SPONTANEOUS CP VIOLATION AND QUARK MASS AMBIGUITIES.

    Energy Technology Data Exchange (ETDEWEB)

    CREUTZ,M.

    2004-09-21

    I explore the regions of quark masses where CP will be spontaneously broken in the strong interactions. The boundaries of these regions are controlled by the chiral anomaly, which manifests itself in ambiguities in the definition of non-degenerate quark masses. In particular, the concept of a single massless quark is ill defined.

  3. 1 INFLUENCE OF SPONTANEOUS FERMENTATION ON SOME ...

    African Journals Online (AJOL)

    RopSvr

    Spontaneous fermentation has been identified to improve the quality characteristics of foods derived from them. When combined with cowpea fortification and nixtamalization, it is expected to improve the nutritional, functional, physico-chemical and sensory qualities of maize based foods thereby improving the qualities as ...

  4. Association between Nutritional Status with Spontaneous Abortion

    Directory of Open Access Journals (Sweden)

    Rahimeh Ahmadi

    2016-11-01

    Full Text Available Background: Spontaneous abortion is the most common adverse pregnancy outcome. We aimed to investigate a possible link between nutrient deficiencies and the risk of spontaneous abortion. Materials and Methods: This case-control study included the case group (n=331 experiencing a spontaneous abortion before 14 weeks of pregnancy and the control group (n=331 who were healthy pregnant women over 14 weeks of pregnancy. The participants filled out Food Frequency Questionnaire (FFQ, in which they reported their frequency of consumption for a given serving of each food item during the past three months, on a daily, weekly or monthly basis. The reported frequency for each food item was converted to a daily intake. Then, consumption of nutrients was compared between the two groups. Results: There are significant differences between the two groups regarding consumed servings/day of vegetables, bread and cereal, meat, poultry, fish, eggs, beans, fats, oils and dairy products (P=0.012, P<0.001, P=0.004, P<0.001, P=0.019, respectively. There are significant differences between the two groups in all micronutrient including folic acid, iron, vitamin C, vitamin B6, vitamin B12 and zinc (P<0.001. Conclusion: Poor nutrientions may be correlated with increased risk of spontaneous abortion

  5. Spontaneous regression of an intraspinal disc cyst

    Energy Technology Data Exchange (ETDEWEB)

    Demaerel, P.; Eerens, I.; Wilms, G. [University Hospital, Leuven (Belgium). Dept. of Radiology; Goffin, J. [Dept. of Neurosurgery, University Hospitals, Leuven (Belgium)

    2001-11-01

    We present a patient with a so-called disc cyst. Its location in the ventrolateral epidural space and its communication with the herniated disc are clearly shown. The disc cyst developed rapidly and regressed spontaneously. This observation, which has not been reported until now, appears to support focal degeneration with cyst formation as the pathogenesis. (orig.)

  6. Spontaneous rupture of an infected renal cyst

    Energy Technology Data Exchange (ETDEWEB)

    Kopp, W.; Toelly, E.; Ebner, F.; Kullnig, P.

    1986-07-01

    Spontaneous or traumatic rupture of renal cysts is a rare occurrence. The contents of the cyst can perforate into the renal calyx system or into the perirenal space. Perforation into the peritoneal cavity has also been described (1, 2, 4, 5).

  7. Proteomic Biomarkers for Spontaneous Preterm Birth

    DEFF Research Database (Denmark)

    Kacerovsky, Marian; Lenco, Juraj; Musilova, Ivana

    2014-01-01

    This review aimed to identify, synthesize, and analyze the findings of studies on proteomic biomarkers for spontaneous preterm birth (PTB). Three electronic databases (Medline, Embase, and Scopus) were searched for studies in any language reporting the use of proteomic biomarkers for PTB published...

  8. Spontaneous emission from saturated parametric amplifiers

    DEFF Research Database (Denmark)

    Rottwitt, Karsten; Ott, Johan Raunkjær; Steffensen, Henrik

    2009-01-01

    Noise performance of parametric amplifiers is typically calculated assuming un-depleted operation. However, in many applications especially when applied as regenerative amplifiers in systems based on phase shift keyed modulation schemes, this assumption is not valid. Here we show the impact...... on accumulated spontaneous emission for a parametric amplifier operated in saturation....

  9. Spontaneous Non-verbal Counting in Toddlers

    Science.gov (United States)

    Sella, Francesco; Berteletti, Ilaria; Lucangeli, Daniela; Zorzi, Marco

    2016-01-01

    A wealth of studies have investigated numerical abilities in infants and in children aged 3 or above, but research on pre-counting toddlers is sparse. Here we devised a novel version of an imitation task that was previously used to assess spontaneous focusing on numerosity (i.e. the predisposition to grasp numerical properties of the environment)…

  10. Editorial: Spontaneous bacterial peritonitis | Lule | East African ...

    African Journals Online (AJOL)

    Journal Home > Vol 81, No 3 (2004) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register. Editorial: Spontaneous bacterial peritonitis. GN Lule. Abstract. No Abstract Available. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT ...

  11. Spontaneous conversion of first onset atrial fibrillation

    DEFF Research Database (Denmark)

    Lindberg, Søren Østergaard; Hansen, Sidsel; Nielsen, Tonny

    2011-01-01

    Background  We studied all patients admitted to hospital with first onset atrial fibrillation (AF) to determine the probability of spontaneous conversion to sinus rhythm and to identify factors predictive of such a conversion. Methods and Results  We retrospectively reviewed charts of 438...

  12. Spontaneous dimensional reduction in quantum gravity

    Science.gov (United States)

    Carlip, S.

    2016-07-01

    Hints from a number of different approaches to quantum gravity point to a phenomenon of “spontaneous dimensional reduction” to two spacetime dimensions near the Planck scale. I examine the physical meaning of the term “dimension” in this context, summarize the evidence for dimensional reduction, and discuss possible physical explanations.

  13. Surgical management of spontaneous ruptured hepatocellular adenoma

    Directory of Open Access Journals (Sweden)

    Marcelo Augusto Fontenelle Ribeiro Junior

    2009-01-01

    Full Text Available AIMS: Spontaneous ruptured hepatocellular adenoma (SRHA is a rare life-threatening condition that may require surgical treatment to control hemorrhaging and also stabilize the patient. We report a series of emergency surgeries performed at our institution for this condition. METHODS: We reviewed medical records and radiology files of 28 patients (from 1989 to 2006 with a proven diagnosis of hepatocellular adenoma (HA. Three (10.7% of 28 patients had spontaneous ruptured hepatocellular adenoma, two of which were associated with intrahepatic hemorrhage while one had intraperitoneal bleeding. Two patients were female and one was male. Both female patients had a background history of oral contraceptive use. Sudden abdominal pain associated with hemodynamic instability occurred in all patients who suffered from spontaneous ruptured hepatocellular adenoma. The mean age was 41.6 years old. The preoperative assessment included liver function tests, ultrasonography and computed tomography. RESULTS: The surgical approaches were as follows: right hemihepatectomy for controlling intraperitoneal bleeding, and right extended hepatectomy and non-anatomic resection of the liver for intrahepatic hemorrhage. There were no deaths, and the postoperative complications were bile leakage and wound infection (re-operation, as well as intraperitoneal abscess (re-operation and pleural effusion. CONCLUSION: Spontaneous ruptured hepatocellular adenoma may be treated by surgery for controlling hemorrhages and stabilizing the patient, and the decision to operate depends upon both the patient's condition and the expertise of the surgical team.

  14. Chronic Allium sativum administration alters spontaneous ...

    African Journals Online (AJOL)

    This study was conducted to investigate the effects of Allium sativum extract on the medial prefrontal cortex and neurobehaviour of adult Wistar rats. ... altered spontaneous alternation, while cellular pathologic changes were observed in the medial prefrontal cortex of these test groups in a dose dependent sequence.

  15. Spontaneous hedonic reactions to social media cues

    NARCIS (Netherlands)

    Koningsbruggen, G.M. van; Hartmann, T.; Eden, A.; Veling, H.P.

    2017-01-01

    Why is it so difficult to resist the desire to use social media? One possibility is that frequent social media users possess strong and spontaneous hedonic reactions to social media cues, which, in turn, makes it difficult to resist social media temptations. In two studies (total N = 200), we

  16. Recurrent spontaneous intracerebral hemorrhage associated with ...

    African Journals Online (AJOL)

    Spontaneous intracerebral hemorrhage (ICH) accounts for 15% of stroke cases in the US and Europe and up to 30% in Asian populations. Intracerebral hemorrhage is a relatively uncommon form of stroke-it causes only 10 to 15 percent of all strokes. It is more disabling and has a higher mortality rate than ischemic stroke, ...

  17. Ovarian hyperstimulation syndrome in a spontaneous pregnancy ...

    African Journals Online (AJOL)

    It is known that most cases of Ovarian Hyperstimulation Syndrome (OHSS) are associated with the therapies for ovulation induction. However, OHSS may rarely be associated with a spontaneous ovulatory cycle, usually in the case of multiple gestations, hypothyroidism or polycystic ovary syndrome. We report a case of ...

  18. Spontaneous left main coronary artery dissection

    Directory of Open Access Journals (Sweden)

    Alptug Tokatli

    2016-03-01

    Full Text Available Spontaneous coronary artery dissection (SCAD is a very rare clinical condition. Physiopathology of SCAD is still mostly unclear. Clinical presentation of SCAD ranges from atypical symptoms to sudden cardiac death. The diagnosis of dissection is generally made by using conventional coronary angiography. Invasive or conservative treatment is reasonable.

  19. Spontaneous extracranial decompression of epidural hematoma

    International Nuclear Information System (INIS)

    Neely, John C.; Jones, Blaise V.; Crone, Kerry R.

    2008-01-01

    Epidural hematoma (EDH) is a common sequela of head trauma in children. An increasing number are managed nonsurgically, with close clinical and imaging observation. We report the case of a traumatic EDH that spontaneously decompressed into the subgaleal space, demonstrated on serial CT scans that showed resolution of the EDH and concurrent enlargement of the subgaleal hematoma. (orig.)

  20. Spontaneous extracranial decompression of epidural hematoma

    Energy Technology Data Exchange (ETDEWEB)

    Neely, John C. [Marshall University School of Medicine, Huntington, WV (United States); Jones, Blaise V. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Crone, Kerry R. [Cincinnati Children' s Hospital Medical Center, Division of Neurosurgery, Cincinnati, OH (United States)

    2008-03-15

    Epidural hematoma (EDH) is a common sequela of head trauma in children. An increasing number are managed nonsurgically, with close clinical and imaging observation. We report the case of a traumatic EDH that spontaneously decompressed into the subgaleal space, demonstrated on serial CT scans that showed resolution of the EDH and concurrent enlargement of the subgaleal hematoma. (orig.)

  1. Spontaneous Sourcing among Students Reading Multiple Documents

    Science.gov (United States)

    Stromso, Helge I.; Braten, Ivar; Britt, M. Anne; Ferguson, Leila E.

    2013-01-01

    This study used think-aloud methodology to explore undergraduates' spontaneous attention to and use of source information while reading six documents that presented conflicting views on a controversial social scientific issue in a Google-like environment. Results showed that students explicitly and implicitly paid attention to sources of documents…

  2. Massive Spontaneous Hemothorax, Giant Intrathoracic Meningocele ...

    African Journals Online (AJOL)

    haemothorax associated with von Recklinghausen's disease: Review of occurrence in Japan. Thorax 1997;52:575‑8. 3. Fedoruk LM, English J, Fradet GJ. Spontaneous hemothorax and neurofibromatosis: A review of a lethal combination. Asian Cardiovasc. Thorac Ann 2007;15:342‑4. 4. Conlon NP, Redmond KC, Celi LA.

  3. A Fatal Complication of Dermatomyositis: Spontaneous Pneumomediastinum

    Directory of Open Access Journals (Sweden)

    Ezgi Demirdöğen Çetinoğlu

    2016-04-01

    Full Text Available Interstitial lung disease (ILD is a negative prognostic factor associated with increased morbidity and mortality in patients with dermatomyositis (DM. Spontaneous pneumomediastinum is a rare complication of DM and it can be fatal. We present a 48-year-old woman with DM and ILD complicated by pneumomediastinum without pneumothorax and subcutaneous emphysema.

  4. Grooming behavior of spontaneously hypertensive rats

    NARCIS (Netherlands)

    Buuse, M. van den; Jong, Wybren de

    1987-01-01

    In an open field spontaneously hypertensive rats (SHR) exhibited lower scores for grooming when compared to their normotensive controls, the Wistar Kyoto rats (WKY). After i.c.v. injection of 1 μg ACTH1–24 cumulative 50-min grooming scores were lower in SHR. Analysis of subscores indicated that the

  5. Spontaneous abortion and physical strain around implantation

    DEFF Research Database (Denmark)

    Hjollund, N H; Jensen, Tina Kold; Bonde, Jens Peter

    2000-01-01

    Existing studies of physical strain and spontaneous abortion are mainly retrospective or based only on pregnancies that have survived the first trimester. Furthermore, almost all studies have relied on averaged measures of physical strain, which tend to blur an effect if peak values during short ...

  6. Spontaneous Hedonic Reactions to Social Media Cues.

    Science.gov (United States)

    van Koningsbruggen, Guido M; Hartmann, Tilo; Eden, Allison; Veling, Harm

    2017-05-01

    Why is it so difficult to resist the desire to use social media? One possibility is that frequent social media users possess strong and spontaneous hedonic reactions to social media cues, which, in turn, makes it difficult to resist social media temptations. In two studies (total N = 200), we investigated less-frequent and frequent social media users' spontaneous hedonic reactions to social media cues using the Affect Misattribution Procedure-an implicit measure of affective reactions. Results demonstrated that frequent social media users showed more favorable affective reactions in response to social media (vs. control) cues, whereas less-frequent social media users' affective reactions did not differ between social media and control cues (Studies 1 and 2). Moreover, the spontaneous hedonic reactions to social media (vs. control) cues were related to self-reported cravings to use social media and partially accounted for the link between social media use and social media cravings (Study 2). These findings suggest that frequent social media users' spontaneous hedonic reactions in response to social media cues might contribute to their difficulties in resisting desires to use social media.

  7. Spontaneous electric fields in solid films: spontelectrics

    DEFF Research Database (Denmark)

    Field, David; Plekan, Oksana; Cassidy, Andrew

    2013-01-01

    When dipolar gases are condensed at sufficiently low temperature onto a solid surface, they form films that may spontaneously exhibit electric fields in excess of 108V/m. This effect, called the ‘spontelectric effect’, was recently revealed using an instrument designed to measure scattering...

  8. Spontaneous Retroperitoneal Hemorrhage from Adrenal Artery Aneurysm

    International Nuclear Information System (INIS)

    Gonzalez Valverde, F.M.; Balsalobre, M.; Torregrosa, N.; Molto, M.; Gomez Ramos, M.J.; Vazquez Rojas, J.L.

    2007-01-01

    Spontaneous adrenal hemorrhage is a very rare but serious disorder of the adrenal gland that can require emergent treatment. We report on a 42-year-old man who underwent selective angiography for diagnosis and treatment of retroperitoneal hemorrhage from small adrenal artery aneurysm. This case gives further details about the value of transluminal artery embolization in the management of visceral aneurysm rupture

  9. Individual differences in spontaneous analogical transfer.

    Science.gov (United States)

    Kubricht, James R; Lu, Hongjing; Holyoak, Keith J

    2017-05-01

    Research on analogical problem solving has shown that people often fail to spontaneously notice the relevance of a semantically remote source analog when solving a target problem, although they are able to form mappings and derive inferences when given a hint to recall the source. Relatively little work has investigated possible individual differences that predict spontaneous transfer, or how such differences may interact with interventions that facilitate transfer. In this study, fluid intelligence was measured for participants in an analogical problem-solving task, using an abridged version of the Raven's Progressive Matrices (RPM) test. In two experiments, we systematically compared the effect of augmenting verbal descriptions of the source with animations or static diagrams. Solution rates to Duncker's radiation problem were measured across varying source presentation conditions, and participants' understanding of the relevant source material was assessed. The pattern of transfer was best fit by a moderated mediation model: the positive impact of fluid intelligence on spontaneous transfer was mediated by its influence on source comprehension; however, this path was in turn modulated by provision of a supplemental animation via its influence on comprehension of the source. Animated source depictions were most beneficial in facilitating spontaneous transfer for those participants with low scores on the fluid intelligence measure.

  10. Spontaneous regression of a mandibular arteriovenous malformation

    Directory of Open Access Journals (Sweden)

    Scott B. Raymond, MD, PhD

    2015-06-01

    Full Text Available Mandibular arteriovenous malformations (AVMs are rare lesions that may initially present as catastrophic bleeding during dental surgical procedures. Owing to the significant risk of bleeding, most mandibular AVMs are treated definitively by resection or embolization. In this report, we describe a mandibular AVM that spontaneously regressed after biopsy.

  11. Unified gauge theories with spontaneous symmetry breaking

    International Nuclear Information System (INIS)

    MacDowell, S.W.

    1975-01-01

    Unified gauge theories with spontaneous symmetry breaking are studied with a view to renormalize quantum field theory. Georgi-Glashow and Weinberg-Salam models to unify weak and electromagnetic interactions are discussed in detail. Gauge theories of strong interactions are also considered [pt

  12. Influence of spontaneous fermentation on some quality ...

    African Journals Online (AJOL)

    Spontaneous fermentation has been identified to improve the quality characteristics of foods derived from them. When combined with cowpea fortification and nixtamalization, it is expected to improve the nutritional, functional, physico- chemical and sensory qualities of maize based foods thereby improving the qualities as ...

  13. Maternal Factors Associated With Early Spontaneous Singleton ...

    African Journals Online (AJOL)

    Background: Knowledge of the maternal factors predisposing to preterm deliveries should affect the anticipatory care of mothers at risk of delivering preterm babies and improve perinatal outcome. Objective: To determine the maternal socio-biological characteristics associated with the delivery of early spontaneous ...

  14. PERIODIC-SOLUTIONS IN SPONTANEOUSLY BROKEN THEORIES

    NARCIS (Netherlands)

    BRIHAYE, Y; KUNZ, J

    A class of spontaneously broken field theories is proposed, and the occurrence of their periodic, classical solutions is investigated in detail. The emergence of multiple solutions is observed, their normal modes of oscillation are studied, and the bifurcations of the classical energy functional are

  15. Spontaneous sensorimotor coupling with multipart music.

    Science.gov (United States)

    Hurley, Brian K; Martens, Peter A; Janata, Petr

    2014-08-01

    Music often evokes spontaneous movements in listeners that are synchronized with the music, a phenomenon that has been characterized as being in "the groove." However, the musical factors that contribute to listeners' initiation of stimulus-coupled action remain unclear. Evidence suggests that newly appearing objects in auditory scenes orient listeners' attention, and that in multipart music, newly appearing instrument or voice parts can engage listeners' attention and elicit arousal. We posit that attentional engagement with music can influence listeners' spontaneous stimulus-coupled movement. Here, 2 experiments-involving participants with and without musical training-tested the effect of staggering instrument entrances across time and varying the number of concurrent instrument parts within novel multipart music on listeners' engagement with the music, as assessed by spontaneous sensorimotor behavior and self-reports. Experiment 1 assessed listeners' moment-to-moment ratings of perceived groove, and Experiment 2 examined their spontaneous tapping and head movements. We found that, for both musically trained and untrained participants, music with more instruments led to higher ratings of perceived groove, and that music with staggered instrument entrances elicited both increased sensorimotor coupling and increased reports of perceived groove. Although untrained participants were more likely to rate music as higher in groove, trained participants showed greater propensity for tapping along, and they did so more accurately. The quality of synchronization of head movements with the music, however, did not differ as a function of training. Our results shed new light on the relationship between complex musical scenes, attention, and spontaneous sensorimotor behavior.

  16. Swimming exercise reverses aging-related contractile abnormalities of female heart by improving structural alterations.

    Science.gov (United States)

    Ozturk, Nihal; Olgar, Yusuf; Er, Hakan; Kucuk, Murathan; Ozdemir, Semir

    2017-01-01

    The objective of this study was to examine the effect of swimming exercise on aging-related Ca2+ handling alterations and structural abnormalities of female rat heart. For this purpose, 4-month and 24-month old female rats were used and divided into three following groups: sedentary young (SY), sedentary old (SO), and exercised old (Ex-O). Swimming exercise was performed for 8 weeks (60 min/day, 5 days/week). Myocyte shortening, L-type Ca2+ currents and associated Ca2+ transients were measured from ventricular myocytes at 36 ± 1°C. NOX-4 levels, aconitase activity, glutathione measurements and ultrastructural examination by electron microscopy were conducted in heart tissue. Swimming exercise reversed the reduced shortening and slowed kinetics of aged cardiomyocytes. Although the current density was similar for all groups, Ca2+ transients were higher in SO and Ex-O myocytes with respect to the SY group. Caffeine-induced Ca2+ transients and the integrated NCX current were lower in cardiomyocytes of SY rats compared with other groups, suggesting an increased sarcoplasmic reticulum Ca2+ content in an aged heart. Aging led to upregulated cardiac NOX-4 along with declined aconitase activity. Although it did not reverse these oxidative parameters, swimming exercise achieved a significant increase in glutathione levels and improved structural alterations of old rats' hearts. We conclude that swimming exercise upregulates antioxidant defense capacity and improves structural abnormalities of senescent female rat heart, although it does not change Ca2+ handling alterations further. Thereby, it improves contractile function of aged myocardium by mitigating detrimental effects of oxidative stress.

  17. β-Citronellol, an alcoholic monoterpene with inhibitory properties on the contractility of rat trachea

    Directory of Open Access Journals (Sweden)

    T.B. Vasconcelos

    2016-01-01

    Full Text Available β-Citronellol is an alcoholic monoterpene found in essential oils such Cymbopogon citratus (a plant with antihypertensive properties. β-Citronellol can act against pathogenic microorganisms that affect airways and, in virtue of the popular use of β-citronellol-enriched essential oils in aromatherapy, we assessed its pharmacologic effects on the contractility of rat trachea. Contractions of isolated tracheal rings were recorded isometrically through a force transducer connected to a data-acquisition device. β-Citronellol relaxed sustained contractions induced by acetylcholine or high extracellular potassium, but half-maximal inhibitory concentrations (IC50 for K+-elicited stimuli were smaller than those for cholinergic contractions. It also inhibited contractions induced by electrical field stimulation or sodium orthovanadate with pharmacologic potency equivalent to that seen against acetylcholine-induced contractions. When contractions were evoked by selective recruitment of Ca2+ from the extracellular medium, β-citronellol preferentially inhibited contractions that involved voltage-operated (but not receptor-operated pathways. β-Citronellol (but not verapamil inhibited contractions induced by restoration of external Ca2+ levels after depleting internal Ca2+ stores with the concomitant presence of thapsigargin and recurrent challenge with acetylcholine. Treatment of tracheal rings with L-NAME, indomethacin or tetraethylammonium did not change the relaxing effects of β-citronellol. Inhibition of transient receptor potential vanilloid subtype 1 (TRPV1 or transient receptor potential ankyrin 1 (TRPA1 receptors with selective antagonists caused no change in the effects of β-citronellol. In conclusion, β-citronellol exerted inhibitory effects on rat tracheal rings, with predominant effects on contractions that recruit Ca2+ inflow towards the cytosol by voltage-gated pathways, whereas it appears less active against contractions elicited by

  18. Modulation of Cardiac Contractility – a New Method in the Treatment of Heart Failure

    Directory of Open Access Journals (Sweden)

    A. A. Petrukhina

    2016-01-01

    Full Text Available The review analyzes new treatment for patients with chronic heart failure (CHF with low ejection fraction – cardiac contractility modulation (CCM. CCM is carried out by supplying electric signals to an absolutely refractory ventricular myocardium, to elicit a positive inotropic effect without increasing myocardial oxygen consumption. These effects are independent on QRS duration; consequently, the therapy might be beneficial for patients who are not candidates for cardiac resynchronization therapy (CRT. It should be noted that the use of CCM treatment of CHF should begin only with maximum active therapy when its efficacy is not enough. It is not an alternative, but complement to the most active treatment of patients. Clinical studies primarily focused on patients with normal QRS duration because the CPT is optimal treatment of patients with prolonged QRS. The article focuses on the prerequisites for the development of the method and discusses the results obtained when evaluating the clinical efficacy and safety of treatment of patients with CHF in randomized clinical trials FIX-HF-3 (n=25, FIX-HF-4 (n=164, FIX-HF-5 (n=428. The total number of patients included into these studies was 617 people. Baseline patient characteristics were similar for all 3 studies. All participants received optimal medical therapy, had a normal QRS duration. All patients were II and III functional class (by NYHA. The studies analyzed the changes in NYHA class, ejection fraction, peak oxygen consumption (VO2, the precursor of brain natriuretic peptide (NT-proBNP level. Quality of life was assessed by the Minnesota questionnaire; the mortality rate was compared with that predicted by MAGGIC scale. CCM therapy had beneficial effect on the survival and quality of life in patients with CHF. However, more data is needed to assess long-term effects of the CCM therapy.

  19. Deletion of Dicer in smooth muscle affects voiding pattern and reduces detrusor contractility and neuroeffector transmission.

    Directory of Open Access Journals (Sweden)

    Mardjaneh Karbalaei Sadegh

    Full Text Available MicroRNAs have emerged as important regulators of smooth muscle phenotype and may play important roles in pathogenesis of various smooth muscle related disease states. The aim of this study was to investigate the role of miRNAs for urinary bladder function. We used an inducible and smooth muscle specific Dicer knockout (KO mouse which resulted in significantly reduced levels of miRNAs, including miR-145, miR-143, miR-22, miR125b-5p and miR-27a, from detrusor preparations without mucosa. Deletion of Dicer resulted in a disturbed micturition pattern in vivo and reduced depolarization-induced pressure development in the isolated detrusor. Furthermore, electrical field stimulation revealed a decreased cholinergic but maintained purinergic component of neurogenic activation in Dicer KO bladder strips. The ultrastructure of detrusor smooth muscle cells was well maintained, and the density of nerve terminals was similar. Western blotting demonstrated reduced contents of calponin and desmin. Smooth muscle α-actin, SM22α and myocardin were unchanged. Activation of strips with exogenous agonists showed that depolarization-induced contraction was preferentially reduced; ATP- and calyculin A-induced contractions were unchanged. Quantitative real time PCR and western blotting demonstrated reduced expression of Cav1.2 (Cacna1c. It is concluded that smooth muscle miRNAs play an important role for detrusor contractility and voiding pattern of unrestrained mice. This is mediated in part via effects on expression of smooth muscle differentiation markers and L-type Ca(2+ channels in the detrusor.

  20. Quantifying inter-species differences in contractile function through biophysical modelling.

    Science.gov (United States)

    Tøndel, Kristin; Land, Sander; Niederer, Steven A; Smith, Nicolas P

    2015-03-01

    Animal models and measurements are frequently used to guide and evaluate clinical interventions. In this context, knowledge of inter-species differences in physiology is crucial for understanding the limitations and relevance of animal experimental assays for informing clinical applications. Extensive effort has been put into studying the structure and function of cardiac contractile proteins and how differences in these translate into the functional properties of muscles. However, integrating this knowledge into a quantitative description, formalising and highlighting inter-species differences both in the kinetics and in the regulation of physiological mechanisms, remains challenging. In this study we propose and apply a novel approach for the quantification of inter-species differences between mouse, rat and human. Assuming conservation of the fundamental physiological mechanisms underpinning contraction, biophysically based computational models are fitted to simulate experimentally recorded phenotypes from multiple species. The phenotypic differences between species are then succinctly quantified as differences in the biophysical model parameter values. This provides the potential of quantitatively establishing the human relevance of both animal-based experimental and computational models for application in a clinical context. Our results indicate that the parameters related to the sensitivity and cooperativity of calcium binding to troponin C and the activation and relaxation rates of tropomyosin/crossbridge binding kinetics differ most significantly between mouse, rat and human, while for example the reference tension, as expected, shows only minor differences between the species. Hence, while confirming expected inter-species differences in calcium sensitivity due to large differences in the observed calcium transients, our results also indicate more unexpected differences in the cooperativity mechanism. Specifically, the decrease in the unbinding rate of