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Sample records for adult rat ventricular

  1. Model of excitation-contraction coupling of rat neonatal ventricular myocytes.

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    Korhonen, Topi; Hänninen, Sandra L; Tavi, Pasi

    2009-02-01

    The neonatal rat ventricular myocyte culture is one of the most popular experimental cardiac cell models. To our knowledge, the excitation-contraction coupling (ECC) of these cells, i.e., the process linking the electrical activity to the cytosolic Ca2+ transient and contraction, has not been previously analyzed, nor has it been presented as a complete system in detail. Neonatal cardiomyocytes are in the postnatal developmental stage, and therefore, the features of their ECC differ vastly from those of adult ventricular myocytes. We present the first complete analysis of ECC in these cells by characterizing experimentally the action potential and calcium signaling and developing the first mathematical model of ECC in neonatal cardiomyocytes that we know of. We show that in comparison to adult cardiomyocytes, neonatal cardiomyocytes have long action potentials, heterogeneous cytosolic Ca2+ signals, weaker sarcoplasmic reticulum Ca2+ handling, and stronger sarcolemmal Ca2+ handling, with a significant contribution by the Na+/Ca2+ exchanger. The developed model reproduces faithfully the ECC of rat neonatal cardiomyocytes with a novel description of spatial cytosolic [Ca2+] signals. Simulations also demonstrate how an increase in the cell size (hypertrophy) affects the ECC in neonatal cardiomyocytes. This model of ECC in developing cardiomyocytes provides a platform for developing future models of cardiomyocytes at different developmental stages.

  2. Influx mechanisms in the embryonic and adult rat choroid plexus

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    Saunders, Norman R; Dziegielewska, Katarzyna M; Møllgård, Kjeld

    2015-01-01

    The transcriptome of embryonic and adult rat lateral ventricular choroid plexus, using a combination of RNA-Sequencing and microarray data, was analyzed by functional groups of influx transporters, particularly solute carrier (SLC) transporters. RNA-Seq was performed at embryonic day (E) 15 and a...

  3. Thallium-201: quantitation of right ventricular hypertrophy in chronically hypoxic rats

    International Nuclear Information System (INIS)

    Rabinovitch, M.; Fisher, K.; Gamble, W.; Reid, L.; Treves, S.

    1979-01-01

    Sprague Dawley rats were divided into two groups. Ten were kept in room air and 10 in hypobaric hypoxia (air at 380 m Hg). After two weeks all were injected intravenously with 50 μCi of 201 Tl and sacrificed. The right and left ventricles were separated, weighed, and measured for radioactivity in a gamma well counter. Left and right ventricular mass ratios (MR) correlated with 201 Tl radioactivity ratios (TAR) in both control and hypoxic rats: r = 0.962 where MR = 0.863 TAR + 0.27. Myocardial 201 Tl uptake reflects and quantitates normal and abnormal ventricular mass, the abnormal mass in this model consisting of right ventricular hypertrophy associated with hypoxic pulmonary hypertension

  4. Dual effect of ethanol on inward rectifier potassium current IK1 in rat ventricular myocytes

    Czech Academy of Sciences Publication Activity Database

    Bébarová, M.; Matejovič, P.; Pásek, Michal; Šimurdová, M.; Šimurda, J.

    2014-01-01

    Roč. 65, č. 4 (2014), s. 497-509 ISSN 0867-5910 Grant - others:GA MZd NT14301 Institutional support: RVO:61388998 Keywords : ethanol * rat ventricular myocyte * rat ventricular action potential model Subject RIV: BO - Biophysics Impact factor: 2.386, year: 2014

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

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

    2018-06-01

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

  6. Possible involvement of mitochondrial energy-producing ability in the development of right ventricular failure in monocrotaline-induced pulmonary hypertensive rats.

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    Daicho, Takuya; Yagi, Tatsuya; Abe, Yohei; Ohara, Meiko; Marunouchi, Tetsuro; Takeo, Satoshi; Tanonaka, Kouichi

    2009-09-01

    The present study was undertaken to explore the possible involvement of alterations in the mitochondrial energy-producing ability in the development of the right ventricular failure in monocrotaline-administered rats. The rats at the 6th week after subcutaneous injection of 60 mg/kg monocrotaline revealed marked myocardial hypertrophy and fibrosis, that is, severe cardiac remodeling. The time-course study on the cardiac hemodynamics of the monocrotaline-administered rat by the cannula and echocardiographic methods showed a reduction in cardiac double product, a decrease in cardiac output index, and an increase in the right ventricular Tei index, suggesting that the right ventricular failure was induced at the 6th week after monocrotaline administration in rats. The mitochondrial oxygen consumption rate of the right ventricular muscle isolated from the monocrotaline-administered animal was decreased, which was associated with a reduction in myocardial high-energy phosphates. Furthermore, the decrease in mitochondrial oxygen consumption rate was inversely related to the increase in the right ventricular Tei index of the monocrotaline-administered rats. These results suggest that impairment of the mitochondrial energy-producing ability is involved in the development of the right ventricular failure in monocrotaline-induced pulmonary hypertensive rats.

  7. Regulatory effect of connexin 43 on basal Ca2+ signaling in rat ventricular myocytes.

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    Chen Li

    Full Text Available BACKGROUND: It has been found that gap junction-associated intracellular Ca(2+ [Ca(2+](i disturbance contributes to the arrhythmogenesis and hyperconstriction in diseased heart. However, whether functional gaps are also involved in the regulation of normal Ca(2+ signaling, in particular the basal [Ca(2+](i activities, is unclear. METHODS AND RESULTS: Global and local Ca(2+ signaling and gap permeability were monitored in cultured neonatal rat ventricular myocytes (NRVMs and freshly isolated mouse ventricular myocytes by Fluo4/AM and Lucifer yellow (LY, respectively. The results showed that inhibition of gap communication by heptanol, Gap 27 and flufenamic acid or interference of connexin 43 (Cx43 with siRNA led to a significant suppression of LY uptake and, importantly, attenuations of global Ca(2+ transients and local Ca(2+ sparks in monolayer NRVMs and Ca(2+ sparks in adult ventricular myocytes. In contrast, overexpression of rat-Cx43 in NRVMs induced enhancements in the above measurements, and so did in HEK293 cells expressing rat Cx43. Additionally, membrane-permeable inositol 1,4,5-trisphosphate (IP(3 butyryloxymethyl ester and phenylephrine, an agonist of adrenergic receptor, could relieve the inhibited Ca(2+ signal and LY uptake by gap uncouplers, whereas blockade of IP(3 receptor with xestospongin C or 2-aminoethoxydiphenylborate mimicked the effects of gap inhibitors. More importantly, all these gap-associated effects on Ca(2+ signaling were also found in single NRVMs that only have hemichannels instead of gap junctions. Further immunostaining/immunoblotting single myocytes with antibody against Cx43 demonstrated apparent increases in membrane labeling of Cx43 and non-junctional Cx43 in overexpressed cells, suggesting functional hemichannels exist and also contribute to the Ca(2+ signaling regulation in cardiomyocytes. CONCLUSIONS: These data demonstrate that Cx43-associated gap coupling plays a role in the regulation of resting Ca(2

  8. Sustained exposure to catecholamines affects cAMP/PKA compartmentalised signalling in adult rat ventricular myocytes.

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    Fields, Laura A; Koschinski, Andreas; Zaccolo, Manuela

    2016-07-01

    In the heart compartmentalisation of cAMP/protein kinase A (PKA) signalling is necessary to achieve a specific functional outcome in response to different hormonal stimuli. Chronic exposure to catecholamines is known to be detrimental to the heart and disrupted compartmentalisation of cAMP signalling has been associated to heart disease. However, in most cases it remains unclear whether altered local cAMP signalling is an adaptive response, a consequence of the disease or whether it contributes to the pathogenetic process. We have previously demonstrated that isoforms of PKA expressed in cardiac myocytes, PKA-I and PKA-II, localise to different subcellular compartments and are selectively activated by spatially confined pools of cAMP, resulting in phosphorylation of distinct downstream targets. Here we investigate cAMP signalling in an in vitro model of hypertrophy in primary adult rat ventricular myocytes. By using a real time imaging approach and targeted reporters we find that that sustained exposure to catecholamines can directly affect cAMP/PKA compartmentalisation. This appears to involve a complex mechanism including both changes in the subcellular localisation of individual phosphodiesterase (PDE) isoforms as well as the relocalisation of PKA isoforms. As a result, the preferential coupling of PKA subsets with different PDEs is altered resulting in a significant difference in the level of cAMP the kinase is exposed to, with potential impact on phosphorylation of downstream targets. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  9. The Change of Left Ventricular Function in Rats with Subclinical Hypothyroid and the Effects of Thyroxine Replacement.

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    Chen, Xuedi; Gao, Cuixia; Gong, Ningning; Wang, Yu; Tian, Limin

    2018-01-01

    The main purpose of this study was to explore the relationships between serca2a, Ryr2, adipokines, and the left ventricular function in the subclinical hypothyroidism with different TSH levels and to determine the impact of L-T4 treatment on these indexes. Sixty-five male Wistar rats were randomly divided into five groups: control group; sHT A, B, and C group; and sHT + T4 group. The sHT rats were induced by methimazole (MMI), and the sHT + T4 rats were administered with L-T4 treatment after 8 weeks of MMI administration. Serum TT4, TSH, APN, chemerin, and TNF- α were detected by radioimmunoassay kits and ELISA kits; left ventricular function was measured by PowerLab system via subclavian artery catheter. The expression of Serca2a, Ryr2, APN, chemerin, and TNF- α were detected by RT-PCR, Western blot, and immunohistochemistry. The sHT groups had significantly higher TSH, chemerin, and TNF- α and lower Serca2a, Ryr2, and APN. The left ventricular pressure and heart rate in sHT groups were significantly lower in control and sHT + T4 group. Histopathological examination revealed the pathological changes in the sHT rats' heart. L-T4 administration reduced TSH level and improved left ventricular function. TSH can impair left ventricular function by regulating several factors, and L-T4 treatment ameliorates it in sHT rats.

  10. Contemporary Assessment of Left Ventricular Diastolic Function in Older Adults

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    Shah, Amil M.; Claggett, Brian; Kitzman, Dalane

    2017-01-01

    Background: Although age-Associated changes in left ventricular diastolic function are well recognized, limited data exist characterizing measures of diastolic function in older adults, including both reference ranges reflecting the older adult population and prognostically relevant values...

  11. Hemoglobin A1c and arterial and ventricular stiffness in older adults.

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    Susan J Zieman

    Full Text Available Arterial and ventricular stiffening are characteristics of diabetes and aging which confer significant morbidity and mortality; advanced glycation endproducts (AGE are implicated in this stiffening pathophysiology. We examined the association between HbA(1c, an AGE, with arterial and ventricular stiffness measures in older individuals without diabetes.Baseline HbA(1c was measured in 830 participants free of diabetes defined by fasting glucose or medication use in the Cardiovascular Health Study, a population-based cohort study of adults aged ≥ 65 years. We performed cross-sectional analyses using baseline exam data including echocardiography, ankle and brachial blood pressure measurement, and carotid ultrasonography. We examined the adjusted associations between HbA(1c and multiple arterial and ventricular stiffness measures by linear regression models and compared these results to the association of fasting glucose (FG with like measures.HbA(1c was correlated with fasting and 2-hour postload glucose levels (r = 0.21; p<0.001 for both and positively associated with greater body-mass index and black race. In adjusted models, HbA(1c was not associated with any measure of arterial or ventricular stiffness, including pulse pressure (PP, carotid intima-media thickness, ankle-brachial index, end-arterial elastance, or left ventricular mass (LVM. FG levels were positively associated with systolic, diastolic and PP and LVM.In this sample of older adults without diabetes, HbA(1c was not associated with arterial or ventricular stiffness measures, whereas FG levels were. The role of AGE in arterial and ventricular stiffness in older adults may be better assessed using alternate AGE markers.

  12. Paeoniflorin improves cardiac function and decreases adverse postinfarction left ventricular remodeling in a rat model of acute myocardial infarction

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    Chen H

    2018-04-01

    Full Text Available Hengwen Chen,* Yan Dong,* Xuanhui He, Jun Li, Jie Wang Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China *These authors contributed equally to this work Background: Paeoniflorin (PF is the active component of Paeonia lactiflora Pall. or Paeonia veitchii Lynch. This study was, therefore, aimed to evaluate the improvement and mechanism of the PF on ventricular remodeling in rats with acute myocardial infarction (AMI. Materials and methods: In this study, AMI model was established by ligating the anterior descending coronary artery in Wistar rats. After 4 weeks gavage of PF, the apparent signs and the left ventricle weight index of Wistar rats were observed. The left ventricular ejection fraction (LVEF was evaluated by Doppler ultrasonography. Changes in cardiac morphology were observed by pathologic examination, and apoptosis was observed by the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. In addition, enzyme-linked immunosorbent assay was used to detect the expression of tumor necrosis factor-α (TNF-α, interleukin-6 (IL-6 interleukin-10 (IL-10 and brain natriuretic peptide (BNP. Immunohistochemistry and Western blot method were applied to detect Caspase-3 and Caspase-9. Results: Compared with the model control, the survival conditions of rats in all treatment groups were generally improved after PF treatment. LVEF was significantly increased, and both left ventricular end-diastolic inner diameter and left ventricular end-systolic inner diameter were significantly reduced. Moreover, pathologic examination showed that the myocardium degeneration of the rats treated with PF was decreased, including neater arrangement, more complete myofilament, more uniform gap and less interstitial collagen fibers. Furthermore, the mitochondrial structure of cardiomyocytes was significantly improved. The ultrastructure was clear, and the arrangement of myofilament was more regular. Also, the expression of

  13. Hemodynamic, morphometric and autonomic patterns in hypertensive rats - renin-angiotensin system modulation

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    Fernanda S. Zamo

    2010-01-01

    Full Text Available BACKGROUND: Spontaneously hypertensive rats develop left ventricular hypertrophy, increased blood pressure and blood pressure variability, which are important determinants of heart damage, like the activation of renin-angiotensin system. AIMS: To investigate the effects of the time-course of hypertension over 1 hemodynamic and autonomic patterns (blood pressure; blood pressure variability; heart rate; 2 left ventricular hypertrophy; and 3 local and systemic Renin-angiotensin system of the spontaneously hypertensive rats. METHODS: Male spontaneously hypertensive rats were randomized into two groups: young (n=13 and adult (n=12. Hemodynamic signals (blood pressure, heart rate, blood pressure variability (BPV and spectral analysis of the autonomic components of blood pressure were analyzed. LEFT ventricular hypertrophy was measured by the ratio of LV mass to body weight (mg/g, by myocyte diameter (μm and by relative fibrosis area (RFA, %. ACE and ACE2 activities were measured by fluorometry (UF/min, and plasma renin activity (PRA was assessed by a radioimmunoassay (ng/mL/h. Cardiac gene expressions of Agt, Ace and Ace2 were quantified by RT-PCR (AU. RESULTS: The time-course of hypertension in spontaneously hypertensive rats increased BPV and reduced the alpha index in adult spontaneously hypertensive rats. Adult rats showed increases in left ventricular hypertrophy and in RFA. Compared to young spontaneously hypertensive rats, adult spontaneously hypertensive rats had lower cardiac ACE and ACE2 activities, and high levels of PRA. No change was observed in gene expression of Renin-angiotensin system components. CONCLUSIONS: The observed autonomic dysfunction and modulation of Renin-angiotensin system activity are contributing factors to end-organ damage in hypertension and could be interacting. Our findings suggest that the management of hypertensive disease must start before blood pressure reaches the highest stable levels and the consequent

  14. Effect of streptozotocin-induced diabetes on left ventricular function in adult rats: an in vivo Pinhole Gated SPECT study

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    Weytjens Caroline

    2007-10-01

    Full Text Available Abstract Background Recent studies have suggested that diabetes mellitus (DM may cause left ventricular (LV dysfunction directly resulting in increased susceptibility to heart failure. Using pinhole collimators and advances in data processing, gated SPECT was recently adapted to image the rat heart. The present study was aimed to assess this new imaging technique for quantifying LV function and remodeling from the Streptozotocin (STZ rat model compared to controls. Methods Twenty one rats were randomly assigned to control or diabetic group. Six months after the induction of diabetes by STZ, Pinhole 99 m Tc-sestamibi gated SPECT was performed for determining rat LV volumes and function. Post-mortem histopathologic analysis was performed to evaluate the determinant of LV remodeling in this model. Results After six months, the normalized to body weight LV End-systolic volume was significantly different in diabetic rats compared to controls (0.46 ± 0.02 vs 0.33 ± 0.03 μL/g; p = 0.01. The normalized LV End-diastolic volume was also different in both groups (1.51 ± 0.03 vs 0.88 ± 0.05 μL/g; p = 0.001 and the normalized stroke volume was significantly higher in STZ-rats (1.05 ± 0.02 vs 0.54 ± 0.06 μL/g; p = 0.001. The muscular fibers were thinner at histology in the diabetic rats (0.44 ± 0.07 vs 0.32 ± 0.06 AU; p = 0.01. Conclusion Pinhole 99 m Tc-sestamibi gated SPECT can successfully be applied for the evaluation of cardiac function and remodeling in STZ-induced diabetic rats. In this model, LV volumes were significantly changed compared to a control population, leading to a LV dysfunction. These findings were consistent with the histopathological abnormalities. Finally, these data further suggest the presence of diabetes cardiomyopathy.

  15. In vivo behavior of 111In-DTPA in rat and mouse after intra-ventricular administration

    International Nuclear Information System (INIS)

    Matsushima, Hiroaki; Kato, Makoto; Sugimura, Yukiharu; Hazue, Masaaki

    1977-01-01

    In vivo behavior of 111 In-DTPA in rat and mouse after intra-ventricular administration was studied. Thus, 50μCi and 35μCi of 111 In-DTPA was injected intraventricularly to rat and mouse respectively. At specific time intervals, the animals were sacrificed, then distribution in organs was determined by radioactivity counting and autoradiographic method. Urinary and fecal excretion were separately collected and excretion rates were estimated. Metabolites in urine of rat were examined with chromatography. A part of 111 In-DTPA injected intra-ventricularly to the animals migrated to subarachnoid space, then radioactivity in cerebrospinal fluid effused into blood with about 1 hr initial half-life. Blood clearance was also rapid, about 1 hr after administration the blood level reached maximum and then decreased showing an initial half-life of about 1 hr. The predominant excretion route in rat was urinary and about 90% and 5% of administered dose were excreted within 48 hr through urine and feces respectively. Judging from the Rf-value of radioactivity peak on chromatograms, 111 In-DTPA seems to be excreted without suffering any metabolic change. Concerning to the behavior of 111 In-DTPA in male and female rat, no difference was observed, and the distribution pattern of 111 In-DTPA in mouse was similar to that of rat. (auth.)

  16. Soybean oil increases SERCA2a expression and left ventricular contractility in rats without change in arterial blood pressure

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    Vassallo Dalton

    2010-05-01

    Full Text Available Abstract Background Our aim was to evaluate the effects of soybean oil treatment for 15 days on arterial and ventricular pressure, myocardial mechanics and proteins involved in calcium handling. Methods Wistar rats were divided in two groups receiving 100 μL of soybean oil (SB or saline (CT i.m. for 15 days. Ventricular performance was analyzed in male 12-weeks old Wistar rats by measuring left ventricle diastolic and systolic pressure in isolated perfused hearts according to the Langendorff technique. Protein expression was measured by Western blot analysis. Results Systolic and diastolic arterial pressures did not differ between CT and SB rats. However, heart rate was reduced in the SB group. In the perfused hearts, left ventricular isovolumetric systolic pressure was higher in the SB hearts. The inotropic response to extracellular Ca2+ and isoproterenol was higher in the soybean-treated animals than in the control group. Myosin ATPase and Na+-K+ATPase activities, the expression of sarcoplasmic reticulum calcium pump (SERCA2a and sodium calcium exchanger (NCX were increased in the SB group. Although the phosfolamban (PLB expression did not change, its phosphorylation at Ser16 was reduced while the SERCA2a/PLB ratio was increased. Conclusions In summary, soybean treatment for 15 days in rats increases the left ventricular performance without affecting arterial blood pressure. These changes might be associated with an increase in the myosin ATPase activity and SERCA2a expression.

  17. Decreasing Compensatory Ability of Concentric Ventricular Hypertrophy in Aortic-Banded Rat Hearts

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    Alexandre Lewalle

    2018-02-01

    Full Text Available The cardiac system compensates for variations in physiological and pathophysiological conditions through a dynamic remodeling at the organ, tissue, and intracellular levels in order to maintain function. However, on longer time scales following the onset of ventricular pressure overload, such remodeling may begin to inhibit physiological function and ultimately lead to heart failure. This progression from compensatory to decompensatory behavior is poorly understood, in particular owing to the absence of a unified perspective of the concomitantly remodeling subsystems. To address this issue, the present study investigates the evolution of compensatory mechanisms, in response to overload, by integrating diffusion-tensor MRI, echocardiography, and intracellular and hemodynamic measurements within consistent computational simulations of aortic-banded rat hearts. This approach allows a comparison of the relative leverage of different cardiac properties (geometry, passive mechanical stiffness, fiber configuration, diastolic and peak calcium concentrations, calcium-binding affinity, and aortic impedance to affect cardiac contraction. Measurements indicate that, following aortic banding, an ejection fraction (EF of 75% was maintained, relative to control rats, despite significant remodeling of the left-ventricular wall thickness (increasing by ~90% over 4 weeks. Applying our framework, we identified the left-ventricular wall thickness (concentric hypertrophy and the intracellular calcium dynamics as playing the dominant roles in preserving EF acutely, whereas the significance of hypertrophy decreased subsequently. This trend suggests an increasing reliance on intracellular mechanisms (average increase ~50%, rather than on anatomical features (average decrease ~60%, to achieve compensation of pump function in the early phase of heart failure.

  18. The impact of exercise on ventricular arrhythmias in adults with tetralogy of Fallot.

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    Ávila, Pablo; Marcotte, François; Dore, Annie; Mercier, Lise-Andrée; Shohoudi, Azadeh; Mongeon, François-Pierre; Mondésert, Blandine; Proietti, Anna; Ibrahim, Reda; Asgar, Anita; Poirier, Nancy; Khairy, Paul

    2016-09-15

    Sudden death of presumed arrhythmic etiology is the leading cause of mortality in adults with tetralogy of Fallot. To assess the impact of exercise on ventricular arrhythmias in adults with tetralogy of Fallot. Adults with repaired tetralogy of Fallot were randomized in a 2:1 ratio to an open-label trial of standard care versus 12weeks of supervised combined aerobic/resistance training with continuous Holter monitoring. Proportion of premature ventricular complexes (PVC) and runs of non-sustained ventricular tachycardia (NSVT) were assessed by mixed and Poisson regression models with generalized estimating equations for repeated measures. A total of 152 Holters were performed in 17 patients, median age 35 (interquartile range [IQR] 28, 42) years, 65% male, 13 of whom were randomized to exercise training. Baseline characteristics were similar between groups. Exercise training resulted in significant increases in peak oxygen uptake (11±19%, p=0.028), metabolic equivalents (11±18%, p=0.027), and exercise duration (8±10%, p=0.009) compared to no changes in controls. Frequent (≥30 per hour) PVCs were present in 46% of patients, couplets in 62%, and 3 to 7 beat runs of NSVT in 31%. The median proportion of PVCs was 1.93‰ (IQR 0.41, 5.89) at baseline and 1.45‰ (IQR 0.08, 2.76) during the initial exercise session (p=0.722), and remained stable over time (ß coefficient=-0.031, p=0.408). Runs of NSVT decreased significantly over time (ß coefficient=-0.032, p=0.018). In adults with repaired tetralogy of Fallot, exercise training is safe, improves exercise capacity, and appears to confer a beneficial effect on ventricular arrhythmias. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Rest and exercise ventricular function in adults with congenital ventricular septal defects

    International Nuclear Information System (INIS)

    Jablonsky, G.; Hilton, J.D.; Liu, P.P.; Morch, J.E.; Druck, M.N.; Bar-Shlomo, B.Z.; McLaughlin, P.R.

    1983-01-01

    Rest and exercise right and left ventricular function were compared using equilibrium gated radionuclide angiography in 19 normal sedentary control subjects and 34 patients with hemodynamically documented congenital ventricular septal defect (VSD). Gated radionuclide angiography was performed at rest and during each level of graded supine bicycle exercise to fatigue. Heart rate, blood pressure, maximal work load achieved, and right and left ventricular ejection fractions were assessed. The control subjects demonstrated an increase in both the left and right ventricular ejection fractions with exercise. All study groups failed to demonstrate an increase in ejection fraction in either ventricle with exercise. Furthermore, resting left ventricular ejection fraction in Groups 2 and 3 was lower than that in the control subjects and resting right ventricular ejection fraction was lower in Group 3 versus control subjects. Thus left and right ventricular function on exercise were abnormal in patients with residual VSD as compared with control subjects; rest and exercise left ventricular ejection fractions remained abnormal despite surgical closure of VSD in the remote past; resting left and right ventricular function was abnormal in patients with Eisenmenger's complex; lifelong volume overload may be detrimental to myocardial function

  20. Fourth ventricular thyrotropin induces satiety and increases body temperature in rats.

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    Smedh, Ulrika; Scott, Karen A; Moran, Timothy H

    2018-05-01

    Besides its well-known action to stimulate thyroid hormone release, thyrotropin mRNA is expressed within the brain, and thyrotropin and its receptor have been shown to be present in brain areas that control feeding and gastrointestinal function. Here, the hypothesis that thyrotropin acts on receptors in the hindbrain to alter food intake and/or gastric function was tested. Fourth ventricular injections of thyrotropin (0.06, 0.60, and 6.00 µg) were given to rats with chronic intracerebroventricular cannulas aimed at the fourth ventricle. Thyrotropin produced an acute reduction of sucrose intake (30 min). The highest dose of thyrotropin caused inhibition of overnight solid food intake (22 h). In contrast, subcutaneous administration of corresponding thyrotropin doses had no effect on nutrient intake. The highest effective dose of fourth ventricular thyrotropin (6 µg) did not produce a conditioned flavor avoidance in a standardized two-bottle test, nor did it affect water intake or gastric emptying of glucose. Thyrotropin injected in the fourth ventricle produced a small but significant increase in rectal temperature and lowered plasma levels of tri-iodothyronin but did not affect plasma levels of thyroxine. In addition, there was a tendency toward a reduction in blood glucose 2 h after fourth ventricular thyrotropin injection ( P = 0.056). In conclusion, fourth ventricular thyrotropin specifically inhibits food intake, increases core temperature, and lowers plasma levels of tri-iodothyronin but does not affect gastromotor function.

  1. The Histological Effects of L-arginine on Ventricular Myocardium in Iron Treated Male Rats

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    M Sofiabadi

    2012-05-01

    Full Text Available

    Background and Objectives: Iron overload is detrimental for the body and can create damage to different body tissues, such as myocardium by producing oxidative stress. Therefore, the antioxidant factors can neutralize iron induced damages. According to available reports, L-arginine as a precursor nitric oxide production has antioxidant effects. This study was carried out to evaluate the histological effects of iron overload on ventricular muscle and preventive role of L-arginine in male rats.
    Methods: In this experiment, 40 male rats with weight range of 300-250g were divided at random into five equal groups including:1- Control, 2- Iron (10mg/kg, ip, 3- Iron(10mg/kg, ip+L-arginine (1mg/ml, po, 4- Iron (50mg/kg, ip and 5- Iron (50mg/kg,ip+L-arginine(1mg/ml,po. After treatment (6 weeks, the animals were anesthetized and the samples of left apical ventricular myocardium were taken out and morphological studies were done following fixation with 10% formalin and H&E staining. Microscopic parameters under study were cell swelling, vessel dilatation and hypercongestion, cell necrosis and tissue deformity. The type and severity of damage to the tissue were also noted. Data were analyzed using chi-square statistical procedure, and Pvalue≤0.05 were considered to be significant. 
    Results: The data showed moderate changes in the ventricular myocardium of group 2 that was significant in comparison to the control group (P<0.05. The ventricular myocardium of group 3 showed low changes and wasn't significant in comparison to control group (P=0.84. The ventricular myocardium of the group 4 showed severe changes in comparison to the control group (P<0.01. The low change showed in the ventricular myocardium of group 5 that wasn't significant in comparison to the control group.

    Conclusion: This study showed

  2. Cerebroventricular Microinjection (CVMI) into Adult Zebrafish Brain Is an Efficient Misexpression Method for Forebrain Ventricular Cells

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    Kizil, Caghan; Brand, Michael

    2011-01-01

    The teleost fish Danio rerio (zebrafish) has a remarkable ability to generate newborn neurons in its brain at adult stages of its lifespan-a process called adult neurogenesis. This ability relies on proliferating ventricular progenitors and is in striking contrast to mammalian brains that have rather restricted capacity for adult neurogenesis. Therefore, investigating the zebrafish brain can help not only to elucidate the molecular mechanisms of widespread adult neurogenesis in a vertebrate species, but also to design therapies in humans with what we learn from this teleost. Yet, understanding the cellular behavior and molecular programs underlying different biological processes in the adult zebrafish brain requires techniques that allow manipulation of gene function. As a complementary method to the currently used misexpression techniques in zebrafish, such as transgenic approaches or electroporation-based delivery of DNA, we devised a cerebroventricular microinjection (CVMI)-assisted knockdown protocol that relies on vivo morpholino oligonucleotides, which do not require electroporation for cellular uptake. This rapid method allows uniform and efficient knockdown of genes in the ventricular cells of the zebrafish brain, which contain the neurogenic progenitors. We also provide data on the use of CVMI for growth factor administration to the brain – in our case FGF8, which modulates the proliferation rate of the ventricular cells. In this paper, we describe the CVMI method and discuss its potential uses in zebrafish. PMID:22076157

  3. The impact of isolated obesity on right ventricular function in young adults.

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    Sokmen, Abdullah; Sokmen, Gulizar; Acar, Gurkan; Akcay, Ahmet; Koroglu, Sedat; Koleoglu, Murat; Yalcintas, Sila; Aydin, M Naci

    2013-08-01

    Obesity is an independent risk factor for cardiovascular diseases. The effects of obesity on left ventricular structure and function have been reported, but relatively little is known regarding right ventricular (RV) function in obesity. To evaluate subclinical RV alterations in obese, but otherwise healthy, young adults by conventional echocardiography and tissue Doppler imaging (TDI). In this study, we included 35 normal weight healthy subjects with a body mass index (BMI) 35 kg/m² (group III). All subjects underwent transthoracic echocardiography. In addition to standard echocardiographic measurements, tricuspid annular peak systolic (Sm), peak early (Em), and late diastolic (Am) velocities, isovolumetric contraction (ICTm), relaxation (IRTm) time, and ejection time (ETm) were obtained by TDI, and RV myocardial performance index (MPIm) was calculated. In group II, RV Em/Am was significantly decreased and IRTm and MPIm were significantly increased compared to group I (p obesity in young normotensive adults was associated with subclinical abnormalities in RV structure and function.

  4. [Intervention of systolic pressure and left ventricular hypertrophy in rats under cold stress].

    Science.gov (United States)

    Sun, C F; Wang, S G; Peng, Y G; Shi, Y; Du, Y P; Shi, G X; Wen, T; Wang, Y K; Su, H

    2016-06-20

    To investigate the effects of different drugs on systolic blood pressure (SBP) and left ventricular hypertrophy (LVH) in spontaneously hypertensive rats under cold stress. A total of 40 male spontaneously hypertensive rats aged 10 weeks (160~200 g) were given adaptive feeding for 7 days at a temperature of 20±1°C and then randomly divided into control group, cold stress group, metoprolol group, amlodipine group, and benazepril group, with 8 rats in each group. SBP, body weight, and heart rate were measured once a week. After the rats were sacrificed by exsanguination, left ventricular weight (LVW) was measured, and left ventricular weight index (LVWI; mg/g) was calculated. Radioimmunoassay was used to measure the concentrations of endothelin-1 (ET-1) and angiotensin-II (Ang-II) in plasma and myocardium, and the chemical method was used to measure the concentrations of nitric oxide (NO) in plasma and myocardium. RT-PCR was used to measure the mRNA expression of endothelin-A receptor. Compared with the cold stress group, all medication groups showed significant reductions in SBP since week 5 (Pcold stress group showed a significant increase in LVWI compared with the control group (3.38±0.27 mg/g vs 2.89±0.19 mg/g, Pcold stress group (2.98±0.28 mg/g vs 3.38±0.27 mg/g, Pcold stress group showed a significant reduction in plasma NO concentration compared with the control group (104.9±19.5 μmol/L vs 129.3±17.8 μmol/L, Pcold stress group, all the medication groups showed significant increases in blood NO concentration (Pcold stress group showed a significant increase in myocardial ET-1 concentration compared with the control group (6.3±1.5 pg/100 mg vs 4.5±1.9 pg/100 mg, Pcold stress group, the amlodipine group showed a significant reduction in myocardial ET-1 concentration (4.4±1.0 pg/100 mg vs 6.3±1.5 pg/100 mg, Pcold stress group had significantly higher mRNA expression of endothelin-A receptor than the control group (0.86±0.23 vs 0.45±0.16, Pcold

  5. Zinc Is Indispensable in Exercise-Induced Cardioprotection against Intermittent Hypoxia-Induced Left Ventricular Function Impairment in Rats.

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    Tsung-I Chen

    Full Text Available In obstructive sleep apnea (OSA, recurrent obstruction of the upper airway leads to intermittent hypoxia (IH during sleep, which can result in impairment of cardiac function. Although exercise can have beneficial effects against IH-induced cardiac dysfunction, the mechanism remains unclear. This study aimed to investigate the interactions of zinc and exercise on IH-triggered left ventricular dysfunction in a rat model that mimics IH in OSA patients. Nine-week-old male Sprague-Dawley rats were randomly assigned to either a control group (CON or to a group receiving 10 weeks of exercise training (EXE. During weeks 9 and 10, half the rats in each group were subjected to IH for 8 h per day for 14 days (IHCON, IHEXE, whereas the remainder continued to breathe room air. Rats within each of the CON, IHCON, EXE, and IHEXE groups were further randomly assigned to receive intraperitoneal injections of either zinc chloride, the zinc chelator N,N,N',N'-tetrakis(2-pyridylmethyl ethylenediamine (TPEN, or injection vehicle only. IH induced a lower left ventricular fractional shortening, reduced ejection fraction, higher myocardial levels of inflammatory factors, increased levels oxidative stress, and lower levels of antioxidative capacity, all of which were abolished by zinc treatment. IHEXE rats exhibited higher levels of cardiac function and antioxidant capacity and lower levels of inflammatory factors and oxidative stress than IHCON rats; however, IHEXE rats receiving TPEN did not exhibit these better outcomes. In conclusion, zinc is required for protecting against IH-induced LV functional impairment and likely plays a critical role in exercise-induced cardioprotection by exerting a dual antioxidant and anti-inflammatory effect.

  6. Zinc Is Indispensable in Exercise-Induced Cardioprotection against Intermittent Hypoxia-Induced Left Ventricular Function Impairment in Rats

    Science.gov (United States)

    Chen, Michael Yu-Chih

    2016-01-01

    In obstructive sleep apnea (OSA), recurrent obstruction of the upper airway leads to intermittent hypoxia (IH) during sleep, which can result in impairment of cardiac function. Although exercise can have beneficial effects against IH-induced cardiac dysfunction, the mechanism remains unclear. This study aimed to investigate the interactions of zinc and exercise on IH-triggered left ventricular dysfunction in a rat model that mimics IH in OSA patients. Nine-week-old male Sprague-Dawley rats were randomly assigned to either a control group (CON) or to a group receiving 10 weeks of exercise training (EXE). During weeks 9 and 10, half the rats in each group were subjected to IH for 8 h per day for 14 days (IHCON, IHEXE), whereas the remainder continued to breathe room air. Rats within each of the CON, IHCON, EXE, and IHEXE groups were further randomly assigned to receive intraperitoneal injections of either zinc chloride, the zinc chelator N,N,N',N'-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN), or injection vehicle only. IH induced a lower left ventricular fractional shortening, reduced ejection fraction, higher myocardial levels of inflammatory factors, increased levels oxidative stress, and lower levels of antioxidative capacity, all of which were abolished by zinc treatment. IHEXE rats exhibited higher levels of cardiac function and antioxidant capacity and lower levels of inflammatory factors and oxidative stress than IHCON rats; however, IHEXE rats receiving TPEN did not exhibit these better outcomes. In conclusion, zinc is required for protecting against IH-induced LV functional impairment and likely plays a critical role in exercise-induced cardioprotection by exerting a dual antioxidant and anti-inflammatory effect. PMID:27977796

  7. Left ventricular hypertrophy in children, adolescents and young adults with sickle cell anemia

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    Gustavo Baptista de Almeida Faro

    2015-10-01

    Full Text Available OBJECTIVE: The aims of this study were to estimate the frequency of left ventricular hypertrophy and to identify variables associated with this condition in under 25-year-old patients with sickle cell anemia.METHODS: A cross-sectional study was performed of children, adolescents and young adults with sickle cell anemia submitted to a transthoracic Doppler echocardiography. The mass of the left ventricle was determined by the formula of Devereux et al. with correction for height, and the percentile curves of gender and age were applied. Individuals with rheumatic and congenital heart disease were excluded. The patients were divided into two groups according to the presence or absence of left ventricular hypertrophy and compared according to clinical, echocardiographic and laboratory variables.RESULTS: A total of 37.6% of the patients had left ventricular hypertrophy in this sample. There was no difference between the groups of patients with and without hypertrophy according to pathological history or clinical characteristics, except possibly for the use of hydroxyurea, more often used in the group without left ventricular hypertrophy. Patients with left ventricular hypertrophy presented larger left atria and lower hemoglobin and hematocrit levels, reticulocyte index and a higher albumin:creatinine ratio in urine.CONCLUSION: Left ventricular hypertrophy was observed in more than one-third of the young patients with sickle cell anemia with this finding being inversely correlated to the hemoglobin and hematocrit levels, and reticulocyte index and directly associated to a higher albumin/creatinine ratio. It is possible that hydroxyurea had had a protective effect on the development of left ventricular hypertrophy.

  8. Comparison between radionuclide ventriculography and echocardiography for quantification of left ventricular systolic function in rats exposed to doxorubicin

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    Oliveira, Luciano Fonseca Lemos de; Carvalho, Eduardo Elias Vieira de; Romano, Minna Moreira Dias; Maciel, Benedito Carlos; Simões, Marcus Vinicius, E-mail: msimoes@fmrp.usp.br [Universidade de Sao Paulo (USP), Ribeirao Preto, SP (Brazil). Centro de Cardiologia; O' Connell, João Lucas; Pulici, Érica Carolina Campos [Universidade Federal de Uberlândia (UFU), MG (Brazil)

    2017-01-15

    Background: Radionuclide ventriculography (RV) is a validated method to evaluate the left ventricular systolic function (LVSF) in small rodents. However, no prior study has compared the results of RV with those obtained by other imaging methods in this context. Objectives: To compare the results of LVSF obtained by RV and echocardiography (ECHO) in an experimental model of cardiotoxicity due to doxorubicin (DXR) in rats. Methods: Adult male Wistar rats serving as controls (n = 7) or receiving DXR (n = 22) in accumulated doses of 8, 12, and 16 mg/kg were evaluated with ECHO performed with a Sonos 5500 Philips equipment (12-MHz transducer) and RV obtained with an Orbiter-Siemens gamma camera using a pinhole collimator with a 4-mm aperture. Histopathological quantification of myocardial fibrosis was performed after euthanasia. Results: The control animals showed comparable results in the LVSF analysis obtained with ECHO and RV (83.5 ± 5% and 82.8 ± 2.8%, respectively, p > 0.05). The animals that received DXR presented lower LVSF values when compared with controls (p < 0.05); however, the LVSF values obtained by RV (60.6 ± 12.5%) were lower than those obtained by ECHO (71.8 ± 10.1%, p = 0.0004) in this group. An analysis of the correlation between the LVSF and myocardial fibrosis showed a moderate correlation when the LVSF was assessed by ECHO (r = -0.69, p = 0.0002) and a stronger correlation when it was assessed by RV (r = -0.79, p < 0.0001). On multiple regression analysis, only RV correlated independently with myocardial fibrosis. Conclusion: RV is an alternative method to assess the left ventricular function in small rodents in vivo. When compared with ECHO, RV showed a better correlation with the degree of myocardial injury in a model of DXR-induced cardiotoxicity. (author)

  9. Comparison between radionuclide ventriculography and echocardiography for quantification of left ventricular systolic function in rats exposed to doxorubicin

    International Nuclear Information System (INIS)

    Oliveira, Luciano Fonseca Lemos de; Carvalho, Eduardo Elias Vieira de; Romano, Minna Moreira Dias; Maciel, Benedito Carlos; Simões, Marcus Vinicius

    2017-01-01

    Background: Radionuclide ventriculography (RV) is a validated method to evaluate the left ventricular systolic function (LVSF) in small rodents. However, no prior study has compared the results of RV with those obtained by other imaging methods in this context. Objectives: To compare the results of LVSF obtained by RV and echocardiography (ECHO) in an experimental model of cardiotoxicity due to doxorubicin (DXR) in rats. Methods: Adult male Wistar rats serving as controls (n = 7) or receiving DXR (n = 22) in accumulated doses of 8, 12, and 16 mg/kg were evaluated with ECHO performed with a Sonos 5500 Philips equipment (12-MHz transducer) and RV obtained with an Orbiter-Siemens gamma camera using a pinhole collimator with a 4-mm aperture. Histopathological quantification of myocardial fibrosis was performed after euthanasia. Results: The control animals showed comparable results in the LVSF analysis obtained with ECHO and RV (83.5 ± 5% and 82.8 ± 2.8%, respectively, p > 0.05). The animals that received DXR presented lower LVSF values when compared with controls (p < 0.05); however, the LVSF values obtained by RV (60.6 ± 12.5%) were lower than those obtained by ECHO (71.8 ± 10.1%, p = 0.0004) in this group. An analysis of the correlation between the LVSF and myocardial fibrosis showed a moderate correlation when the LVSF was assessed by ECHO (r = -0.69, p = 0.0002) and a stronger correlation when it was assessed by RV (r = -0.79, p < 0.0001). On multiple regression analysis, only RV correlated independently with myocardial fibrosis. Conclusion: RV is an alternative method to assess the left ventricular function in small rodents in vivo. When compared with ECHO, RV showed a better correlation with the degree of myocardial injury in a model of DXR-induced cardiotoxicity. (author)

  10. Comparison between Radionuclide Ventriculography and Echocardiography for Quantification of Left Ventricular Systolic Function in Rats Exposed to Doxorubicin

    Directory of Open Access Journals (Sweden)

    Luciano Fonseca Lemos de Oliveira

    Full Text Available Abstract Background: Radionuclide ventriculography (RV is a validated method to evaluate the left ventricular systolic function (LVSF in small rodents. However, no prior study has compared the results of RV with those obtained by other imaging methods in this context. Objectives: To compare the results of LVSF obtained by RV and echocardiography (ECHO in an experimental model of cardiotoxicity due to doxorubicin (DXR in rats. Methods: Adult male Wistar rats serving as controls (n = 7 or receiving DXR (n = 22 in accumulated doses of 8, 12, and 16 mg/kg were evaluated with ECHO performed with a Sonos 5500 Philips equipment (12-MHz transducer and RV obtained with an Orbiter-Siemens gamma camera using a pinhole collimator with a 4-mm aperture. Histopathological quantification of myocardial fibrosis was performed after euthanasia. Results: The control animals showed comparable results in the LVSF analysis obtained with ECHO and RV (83.5 ± 5% and 82.8 ± 2.8%, respectively, p > 0.05. The animals that received DXR presented lower LVSF values when compared with controls (p < 0.05; however, the LVSF values obtained by RV (60.6 ± 12.5% were lower than those obtained by ECHO (71.8 ± 10.1%, p = 0.0004 in this group. An analysis of the correlation between the LVSF and myocardial fibrosis showed a moderate correlation when the LVSF was assessed by ECHO (r = -0.69, p = 0.0002 and a stronger correlation when it was assessed by RV (r = -0.79, p < 0.0001. On multiple regression analysis, only RV correlated independently with myocardial fibrosis. Conclusion: RV is an alternative method to assess the left ventricular function in small rodents in vivo. When compared with ECHO, RV showed a better correlation with the degree of myocardial injury in a model of DXR-induced cardiotoxicity.

  11. Uptake of trace elements in adult and suckling rat lenses

    International Nuclear Information System (INIS)

    Nabekura, Tomohiro; Ito, Yoshimasa; Minami, Takeshi; Hirunuma, Rieko; Enomoto, Shuichi

    2001-01-01

    The uptake of trace elements in the lens was compared in adult and suckling rat lenses. Multitracers, including 15 trace elements, As, Be, Co, Fe, Mn, Rb, Rh, Ru, Sc, Se, Sr, Y, V, Zn, and Zr, were incubated with the lenses for 4 hr and their concentrations in the lens were measured. A high uptake rate of Zn was observed in the lenses of both adult and suckling rats in comparison with those of the other elements, and the Zn concentration in the lens of suckling rats was higher than that of adult rats. The uptake rate of Sr was higher in adult rats than in suckling rats. On the other contrary, Rb and Se concentrations in the lens were higher in suckling rats than in adult rats. The present study suggests that the different mechanisms depending on development serve to transport trace elements into the lens. (author)

  12. (−-Epicatechin Reduces Blood Pressure and Improves Left Ventricular Function and Compliance in Deoxycorticosterone Acetate-Salt Hypertensive Rats

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    Douglas Jackson

    2018-06-01

    Full Text Available (−-Epicatechin (E is a flavanol found in green tea and cocoa and has been shown to attenuate tumour necrosis factor alpha (TNF-α-mediated inflammation, improve nitric oxide levels, promote endothelial nitric oxide synthase (eNOS activation and inhibit NADPH oxidase. This study investigated the effect of 28 days of low epicatechin dosing (1 mg/kg/day on the cardiovascular function of deoxycorticosterone acetate (DOCA-salt hypertensive rats. Wistar rats (n = 120, 8 weeks of age underwent uninephrectomy and were randomised into four groups (uninephrectomy (UNX, UNX + E, DOCA, DOCA + E. DOCA and DOCA + E rats received 1% NaCl drinking water along with subcutaneous injections of 25 mg deoxycorticosterone-acetate (in 0.4 mL of dimethylformamide every fourth day. UNX + E and DOCA + E rats received 1 mg/kg/day of epicatechin by oral gavage. Single-cell micro-electrode electrophysiology, Langendorff isolated-heart assessment and isolated aorta and mesenteric organ baths were used to assess cardiovascular parameters. Serum malondialdehyde concentration was used as a marker of oxidative stress. Myocardial stiffness was increased and left ventricular compliance significantly diminished in the DOCA control group, and these changes were attenuated by epicatechin treatment (p < 0.05. Additionally, the DOCA + E rats showed significantly reduced blood pressure and malondialdehyde concentrations; however, there was no improvement in left ventricular hypertrophy, electrophysiology or vascular function. This study demonstrates the ability of epicatechin to reduce blood pressure, prevent myocardial stiffening and preserve cardiac compliance in hypertrophied DOCA-salt rat hearts.

  13. The Actions of Lyophilized Apple Peel on the Electrical Activity and Organization of the Ventricular Syncytium of the Hearts of Diabetic Rats

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    Elideth Martínez-Ladrón de Guevara

    2016-01-01

    Full Text Available This study was designed to examine the effects of lyophilized red delicious apple peel (RDP on the action potentials (APs and the input resistance-threshold current relationship. The experiments were performed on isolated papillary heart muscles from healthy male rats, healthy male rats treated with RDP, diabetic male rats, and diabetic male rats treated with RDP. The preparation was superfused with oxygenated Tyrode’s solution at 37°C. The stimulation and the recording of the APs, the input resistance, and the threshold current were made using conventional electrophysiological methods. The RDP presented no significant effect in normal rats. Equivalent doses in diabetic rats reduced the APD and ARP. The relationship between input resistance and threshold current established an inverse correlation. The results indicate the following: (1 The functional structure of the cardiac ventricular syncytium in healthy rats is heterogeneous, in terms of input resistance and threshold current. Diabetes further accentuates the heterogeneity. (2 As a consequence, conduction block occurs and increases the possibility of reentrant arrhythmias. (3 These modifications in the ventricular syncytium, coupled with the increase in the ARP, are the adequate substrate so that, with diabetes, the heart becomes more arrhythmogenic. (4 RDP decreases the APD, the ARP, and most syncytium irregularity caused by diabetes.

  14. Effects of valsartan on ventricular arrhythmia induced by programmed electrical stimulation in rats with myocardial infarction

    Science.gov (United States)

    Jiao, Kun-Li; Li, Yi-Gang; Zhang, Peng-Pai; Chen, Ren-Hua; Yu, Yi

    2012-01-01

    Abstract The impact of angiotensin II receptor blockers (ARBs) on electrical remodelling after myocardial infarction (MI) remains unclear. The purpose of the present study was to evaluate the effect of valsartan on incidence of ventricular arrhythmia induced by programmed electrical stimulation (PES) and potential link to changes of myocardial connexins (Cx) 43 expression and distribution in MI rats. Fifty-nine rats were randomly divided into three groups: Sham (n = 20), MI (n = 20) and MI + Val (20 mg/kg/day per gavage, n = 19). After eight weeks, the incidence of PES-induced ventricular tachycardia (VT) and fibrillation (VF) was compared among groups. mRNA and protein expressions of Cx43, angiotensin II type 1 receptor (AT1R) in the LV border zone (BZ) and non-infarct zone (NIZ) were determined by real-time PCR and Western blot, respectively. Connexins 43 protein and collagen distribution were examined by immunohistochemistry in BZ and NIZ sections from MI hearts. Valsartan effectively improved the cardiac function, reduced the prolonged QTc (163.7 ± 3.7 msec. versus 177.8 ± 4.5 msec., P valsartan. The mRNA and protein expressions of Cx43 in BZ were significantly reduced after MI and up-regulated by valsartan. Increased collagen deposition and reduced Cx43 expression in BZ after MI could be partly attenuated by Valsartan. Valsartan reduced the incidence of PES-induced ventricular arrhythmia, this effect was possibly through modulating the myocardial AT1R and Cx43 expression. PMID:22128836

  15. Radiation nephropathy in young and adult rats

    International Nuclear Information System (INIS)

    Jongejan, H.T.; van der Kogel, A.J.; Provoost, A.P.; Molenaar, J.C.

    1987-01-01

    The effects of bilateral kidney irradiation were compared in young and adult rats. During a 1 year period after a single dose of 0, 7.5, 10, 12.5, or 15 Gy on both kidneys, renal function (glomerular filtration rate and effective renal plasma flow), urine composition, and systolic blood pressure were measured periodically. The first changes after irradiation were observed in the glomerular filtration rate and urine osmolality. One month after 10, 12.5, and 15 Gy, glomerular filtration rate (GFR) and urine osmolality had declined below control values in the young rats. After this initial decline, renal function increased at control rate or even more during the third and fourth month after irradiation but decreased progressively thereafter. In the adult rats, GFR and urine osmolality started to decrease 3 months after 10, 12.5, and 15 Gy. A rise in systolic blood pressure and proteinuria started 2-3 months after 12.5 and 15 Gy in both age groups. Early changes in the glomerular filtration rate with a drop in urine osmolality in young rats, occurring during a period of rapid renal development indicated an irradiation-induced inhibition of glomerular and tubular development. Although renal function deteriorated at a later time in adult rats, dose-response relationships obtained in young and adult rats did not show significant differences

  16. Ventricular performance and Na+-K+ ATPase activity are reduced early and late after myocardial infarction in rats

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    I. Stefanon

    2009-10-01

    Full Text Available Myocardial infarction leads to compensatory ventricular remodeling. Disturbances in myocardial contractility depend on the active transport of Ca2+ and Na+, which are regulated by Na+-K+ ATPase. Inappropriate regulation of Na+-K+ ATPase activity leads to excessive loss of K+ and gain of Na+ by the cell. We determined the participation of Na+-K+ ATPase in ventricular performance early and late after myocardial infarction. Wistar rats (8-10 per group underwent left coronary artery ligation (infarcted, Inf or sham-operation (Sham. Ventricular performance was measured at 3 and 30 days after surgery using the Langendorff technique. Left ventricular systolic pressure was obtained under different ventricular diastolic pressures and increased extracellular Ca2+ concentrations (Ca2+e and after low and high ouabain concentrations. The baseline coronary perfusion pressure increased 3 days after myocardial infarction and normalized by 30 days (Sham 3 = 88 ± 6; Inf 3 = 130 ± 9; Inf 30 = 92 ± 7 mmHg; P < 0.05. The inotropic response to Ca2+e and ouabain was reduced at 3 and 30 days after myocardial infarction (Ca2+ = 1.25 mM; Sham 3 = 70 ± 3; Inf 3 = 45 ± 2; Inf 30 = 29 ± 3 mmHg; P < 0.05, while the Frank-Starling mechanism was preserved. At 3 and 30 days after myocardial infarction, ventricular Na+-K+ ATPase activity and contractility were reduced. This Na+-K+ ATPase hypoactivity may modify the Na+, K+ and Ca2+ transport across the sarcolemma resulting in ventricular dysfunction.

  17. The position of the left and right ventricular outlets during septation. A comparison of chicken and rat development

    NARCIS (Netherlands)

    Wagenaar, J. A.; Lamers, W. H.; Los, J. A.

    1986-01-01

    A comparative study was made of the relative position of the outflow tracts of chicken and rat hearts with respect to the ventricles during septation. For this purpose the position of the left and right ventricular outlet including the aortic and pulmonary valve primordia and the left and right

  18. Effect of endurance exercise training on left ventricular size and remodeling in older adults with hypertension.

    Science.gov (United States)

    Turner, M J; Spina, R J; Kohrt, W M; Ehsani, A A

    2000-04-01

    It is not known whether exercise training can induce a reduction of blood pressure (BP) and a regression of left ventricular hypertrophy (LVH) in older hypertensive subjects. This study was designed to determine whether endurance exercise training, by lowering BP, can induce regression of LVH and left ventricular (LV) concentric remodeling in older hypertensive adults. We studied 11 older adults with mild to moderate hypertension (BP 152.0 +/- 2.5/91.3 +/- 1.5 mm Hg, mean +/- SE), 65.5 +/- 1.2 years old, who exercised for 6.8 +/- 3.8 months. Seven sedentary hypertensive (BP 153 +/- 3/89 +/- 2 mm Hg) subjects, 68.5 +/- 1 years old, served as controls. LV size and geometry and function were assessed with the use of two-dimensional echocardiography. Exercise training increased aerobic power by 16% (p hypertension.

  19. Persistence of neoangiogenesis and cardiomyocyte divisions in right ventricular myocardium of rats born and raised in hypoxic conditions.

    NARCIS (Netherlands)

    Moravec, M.; Turek, Z.I.; Moravec, J.

    2002-01-01

    Effects of chronic hypoxia on capillary and myocyte growth were examined in rats born and raised in a low pressure chamber (equivalent of 3500 m a.s.l.). The animals were sacrificed at the age of 3 months and their hearts were used to study right ventricular growth and vascularization. The results

  20. Right Ventricular Endomyocardial Fibrosis Presenting With Ventricular Tachycardia And Apical Thrombus - An Interesting Presentation

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    Amitesh Aggarwal

    2009-11-01

    Full Text Available Endomyocardial fibrosis is a progressive disease of unknown origin affecting children and young adults. It involves inflow portion of right and/or left ventricle and apex. It may be associated with thrombus. Literature regarding right ventricular endomyocardial fibrosis with thrombus is scarce. Here we report a rare case of right ventricular endomyocardial fibrosis presenting as ventricular tachycardia and echocardiographic evidence of apical thrombus. Interestingly there was no pulmonary involvement or evidence of deep venous thrombosis. This case also underscores the importance of urgent echocardiography in diagnosis of obscure cases of ventricular tachycardia.

  1. Effect of ventricular function and volumes on exercise capacity in adults with repaired Tetralogy of Fallot

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    Natalia Dłużniewska

    2018-01-01

    Conclusion: Exercise intolerance in adults with repaired ToF is markedly depressed. The decreased exercise capacity is correlated with impaired RV function and may be associated also with LV dysfunction, which suggests right-to-left ventricular interaction.

  2. Developmental-stage-dependent radiosensitivity of neural cells in the ventricular zone of telencephalon in mouse and rat fetuses

    International Nuclear Information System (INIS)

    Hoshino, K.; Kameyama, Y.

    1988-01-01

    Pregnant ICR mice were treated with single whole-body X-radiation at a dose of 0.24 Gy on day 10, 13, or 15 of gestation. Fetuses were obtained from mothers during 1 and 24 hours after irradiation. Pyknotic cells in the ventricular zone of telencephalon were counted in serial histological sections. Incidence of pyknotic cells peaked during 6 and 9 hours after irradiation in each gestation day group. Then, dose-response curves were obtained 6 hours after 0-0.48 Gy of irradiation. All three dose-response curves showed clear linearity in the dose range lower than 0.24 Gy. Ratios of radiosensitivity estimated from the slopes of dose-response curves in day 10, 13, and 15 groups were 1, 1.4, and 0.4, respectively. These demonstrated that ventricular cells in the day 13 fetal telencephalon were the most radiosensitive among the three different age groups. In order to confirm the presence of the highly radiosensitive stage common to mammalian cerebral cortical histogenesis, pregnant F344 rats were treated with single whole-body gamma-irradiation at a dose of 0.48 Gy on day 13, 14, 15, 17, or 19 of gestation. The incidence of pyknotic cells in the ventricular zone of telencephalon was examined microscopically during 1 and 24 hours after irradiation. The peak incidence was shown 6 hours after irradiation in all the treated groups, and the highest peak incidence was shown in day-15-treated group. The developmental stage of telencephalon of day 15 rat fetuses was comparable to that of day 13 mouse fetuses. Thus, the highest radiosensitivity in terms of acute cell death was shown in the same developmental stage of brain development, i.e., the beginning phase of cerebral cortical histogenesis, in both mice and rats

  3. Effects of Resistance Training on Ventricular Function and Hypertrophy in a Rat Model

    Science.gov (United States)

    Barauna, Valério Garrone; Rosa, Kaleizu Teodoro; Irigoyen, Maria Cláudia; de Oliveira, Edilamar Menezes

    2007-01-01

    Objective: The purpose of this study was to follow the ventricular function and cardiac hypertrophy in rats undergoing a resistance-training program for a period of 3 months. Design: Forty animals were divided into two major groups: control (n=16) and resistance trained (n=24). From the resistance-trained group, 12 animals were resistance trained for 1 month and another 12 for 3 months. The resistance-training protocol was performed with 4 sets of 12 repetitions using 65% to 75% of one repetition maximum (maximum lifted weight with the exercise apparatus). Methods: Echocardiographic analysis was performed at the beginning of the resistance-training period and at the end of each month. The repetition maximum was measured every 2 weeks. Cardiac hypertrophy was determined by echocardiography, by the absolute weight of the cardiac chambers and by histology of the left ventricle. Results: Before resistance training, both groups had similar repetition maximums, ranging from 1.8-fold to 2-fold the body weight; however, at the end of the resistance-training period, the repetition maximum of the resistance-trained group was 6-fold greater than the body weight. The left ventricular mass as assessed by echocardiography was 8%, 12% and 16% larger in the resistance-trained group than in the control group in the first, second and third months, respectively. This hypertrophy showed a similar increase in the interventricular septum and in the free posterior wall mass. There was no reduction in the end-diastolic left ventricular internal diameter during the 3-month resistance-training period. Systolic function did not differ between the groups throughout the resistance-training period. Conclusion: Resistance training induces the development of concentric cardiac hypertrophy without ventricular dysfunction or cavity reduction. Although diastolic function was not completely investigated, we cannot exclude the possibility that resistance training results in diastolic dysfunction. PMID

  4. Correlation of Ventricular Arrhythmogenesis with Neuronal Remodeling of Cardiac Postganglionic Parasympathetic Neurons in the Late Stage of Heart Failure after Myocardial Infarction.

    Science.gov (United States)

    Zhang, Dongze; Tu, Huiyin; Wang, Chaojun; Cao, Liang; Muelleman, Robert L; Wadman, Michael C; Li, Yu-Long

    2017-01-01

    Introduction: Ventricular arrhythmia is a major cause of sudden cardiac death in patients with chronic heart failure (CHF). Our recent study demonstrates that N-type Ca 2+ currents in intracardiac ganglionic neurons are reduced in the late stage of CHF rats. Rat intracardiac ganglia are divided into the atrioventricular ganglion (AVG) and sinoatrial ganglion. Only AVG nerve terminals innervate the ventricular myocardium. In this study, we tested the correlation of electrical remodeling in AVG neurons with ventricular arrhythmogenesis in CHF rats. Methods and Results: CHF was induced in male Sprague-Dawley rats by surgical ligation of the left coronary artery. The data from 24-h continuous radiotelemetry ECG recording in conscious rats showed that ventricular tachycardia/fibrillation (VT/VF) occurred in 3 and 14-week CHF rats but not 8-week CHF rats. Additionally, as an index for vagal control of ventricular function, changes of left ventricular systolic pressure (LVSP) and the maximum rate of left ventricular pressure rise (LV dP/dt max ) in response to vagal efferent nerve stimulation were blunted in 14-week CHF rats but not 3 or 8-week CHF rats. Results from whole-cell patch clamp recording demonstrated that N-type Ca 2+ currents in AVG neurons began to decrease in 8-week CHF rats, and that there was also a significant decrease in 14-week CHF rats. Correlation analysis revealed that N-type Ca 2+ currents in AVG neurons negatively correlated with the cumulative duration of VT/VF in 14-week CHF rats, whereas there was no correlation between N-type Ca 2+ currents in AVG neurons and the cumulative duration of VT/VF in 3-week CHF. Conclusion: Malignant ventricular arrhythmias mainly occur in the early and late stages of CHF. Electrical remodeling of AVG neurons highly correlates with the occurrence of ventricular arrhythmias in the late stage of CHF.

  5. Observational cohort study of ventricular arrhythmia in adults with Marfan syndrome caused by FBN1 mutations.

    Directory of Open Access Journals (Sweden)

    Ali Aydin

    Full Text Available Marfan syndrome is associated with ventricular arrhythmia but risk factors including FBN1 mutation characteristics require elucidation.We performed an observational cohort study of 80 consecutive adults (30 men, 50 women aged 42±15 years with Marfan syndrome caused by FBN1 mutations. We assessed ventricular arrhythmia on baseline ambulatory electrocardiography as >10 premature ventricular complexes per hour (>10 PVC/h, as ventricular couplets (Couplet, or as non-sustained ventricular tachycardia (nsVT, and during 31±18 months of follow-up as ventricular tachycardia (VT events (VTE such as sudden cardiac death (SCD, and sustained ventricular tachycardia (sVT. We identified >10 PVC/h in 28 (35%, Couplet/nsVT in 32 (40%, and VTE in 6 patients (8%, including 3 with SCD (4%. PVC>10/h, Couplet/nsVT, and VTE exhibited increased N-terminal pro-brain natriuretic peptide serum levels(P10/h and Couplet/nsVT also related to increased indexed end-systolic LV diameters (P = .024 and P = .020, to moderate mitral valve regurgitation (P = .018 and P = .003, and to prolonged QTc intervals (P = .001 and P = .006, respectively. Moreover, VTE related to mutations in exons 24-32 (P = .021. Kaplan-Meier analysis corroborated an association of VTE with increased NT-proBNP (P<.001 and with mutations in exons 24-32 (P<.001.Marfan syndrome with causative FBN1 mutations is associated with an increased risk for arrhythmia, and affected persons may require life-long monitoring. Ventricular arrhythmia on electrocardiography, signs of myocardial dysfunction and mutations in exons 24-32 may be risk factors of VTE.

  6. The dorso-lateral recess of the hypothalamic ventricle in neonatal rats.

    Science.gov (United States)

    Menéndez, A; Alvarez-Uría, M

    1987-10-01

    Light and electron microscopy of the hypothalamic ventricle in neonatal rats demonstrate morphological specializations of the ventricular wall at the level of the premammillary region of the third ventricle. The morphological features are: (1) A ventricular recess that we have called the "hypothalamic dorso-lateral recess" (HDR). (2) The presence of intraventricular capillaries near the dorso-lateral recess. (3) The HDR possessing a specialized ependymal lining; this consists of non-ciliated cells with short microvilli and bleb-like processes. (4) The existence of cerebrospinal fluid-contacting neurons within the HDR. (5) The presence of numerous phagocytic supraependymal cells. The HDR is not found in adult rats. This indicates that the dorso-lateral recess may play a physiological role during development.

  7. Congenital left ventricular wall abnormalities in adults detected by gated cardiac multidetector computed tomography: Clefts, aneurysms, diverticula and terminology problems

    International Nuclear Information System (INIS)

    Erol, Cengiz; Koplay, Mustafa; Olcay, Ayhan; Kivrak, Ali Sami; Ozbek, Seda; Seker, Mehmet; Paksoy, Yahya

    2012-01-01

    Objectives: Our aim was to evaluate congenital left ventricular wall abnormalities (clefts, aneurysms and diverticula), describe and illustrate imaging features, discuss terminology problems and determine their prevalence detected by cardiac CT in a single center. Materials and methods: Coronary CT angiography images of 2093 adult patients were evaluated retrospectively in order to determine congenital left ventricular wall abnormalities. Results: The incidence of left ventricular clefts (LVC) was 6.7% (141 patients) and statistically significant difference was not detected between the sexes regarding LVC (P = 0.5). LVCs were single in 65.2% and multiple in 34.8% of patients. They were located at the basal to mid inferoseptal segment of the left ventricle in 55.4%, the basal to mid anteroseptal segment in 24.1%, basal to mid inferior segment in 17% and septal–apical septal segment in 3.5% of cases. The cleft length ranged from 5 to 22 mm (mean 10.5 mm) and they had a narrow connection with the left ventricle (mean 2.5 mm). They were contractile with the left ventricle and obliterated during systole. Congenital left ventricular septal aneurysm that was located just under the aortic valve was detected in two patients (0.1%). No case of congenital left ventricular diverticulum was detected. Conclusion: Cardiac CT allows us to recognize congenital left ventricular wall abnormalities which have been previously overlooked in adults. LVC is a congenital structural variant of the myocardium, is seen more frequently than previously reported and should be differentiated from aneurysm and diverticulum for possible catastrophic complications of the latter two.

  8. Delayed Repolarization Underlies Ventricular Arrhythmias in Rats With Heart Failure and Preserved Ejection Fraction.

    Science.gov (United States)

    Cho, Jae Hyung; Zhang, Rui; Kilfoil, Peter J; Gallet, Romain; de Couto, Geoffrey; Bresee, Catherine; Goldhaber, Joshua I; Marbán, Eduardo; Cingolani, Eugenio

    2017-11-21

    Heart failure with preserved ejection fraction (HFpEF) represents approximately half of heart failure, and its incidence continues to increase. The leading cause of mortality in HFpEF is sudden death, but little is known about the underlying mechanisms. Dahl salt-sensitive rats were fed a high-salt diet (8% NaCl) from 7 weeks of age to induce HFpEF (n=38). Rats fed a normal-salt diet (0.3% NaCl) served as controls (n=13). Echocardiograms were performed to assess systolic and diastolic function from 14 weeks of age. HFpEF-verified and control rats underwent programmed electrical stimulation. Corrected QT interval was measured by surface ECG. The mechanisms of ventricular arrhythmias (VA) were probed by optical mapping, whole-cell patch clamp to measure action potential duration and ionic currents, and quantitative polymerase chain reaction and Western blotting to investigate changes in ion channel expression. After 7 weeks of a high-salt diet, 31 of 38 rats showed diastolic dysfunction and preserved ejection fraction along with signs of heart failure and hence were diagnosed with HFpEF. Programmed electric stimulation demonstrated increased susceptibility to VA in HFpEF rats ( P hearts demonstrated prolonged action potentials ( P hearts. Susceptibility to VA was markedly increased in rats with HFpEF. Underlying abnormalities include QT prolongation, delayed repolarization from downregulation of potassium currents, and multiple reentry circuits during VA. Our findings are consistent with the hypothesis that potassium current downregulation leads to abnormal repolarization in HFpEF, which in turn predisposes to VA and sudden cardiac death. © 2017 American Heart Association, Inc.

  9. Development of acute hydrocephalus does not change brain tissue mechanical properties in adult rats, but in juvenile rats.

    Science.gov (United States)

    Pong, Alice C; Jugé, Lauriane; Bilston, Lynne E; Cheng, Shaokoon

    2017-01-01

    Regional changes in brain stiffness were previously demonstrated in an experimental obstructive hydrocephalus juvenile rat model. The open cranial sutures in the juvenile rats have influenced brain compression and mechanical properties during hydrocephalus development and the extent by which closed cranial sutures in adult hydrocephalic rat models affect brain stiffness in-vivo remains unclear. The aims of this study were to determine changes in brain tissue mechanical properties and brain structure size during hydrocephalus development in adult rat with fixed cranial volume and how these changes were related to brain tissue deformation. Hydrocephalus was induced in 9 female ten weeks old Sprague-Dawley rats by injecting 60 μL of a kaolin suspension (25%) into the cisterna magna under anaesthesia. 6 sham-injected age-matched female SD rats were used as controls. MR imaging (9.4T, Bruker) was performed 1 day before and then at 3 days post injection. T2-weighted anatomical MR images were collected to quantify ventricle and brain tissue cross-sectional areas. MR elastography (800 Hz) was used to measure the brain stiffness (G*, shear modulus). Brain tissue in the adult hydrocephalic rats was more compressed than the juvenile hydrocephalic rats because the skulls of the adult hydrocephalic rats were unable to expand like the juvenile rats. In the adult hydrocephalic rats, the cortical gray matter thickness and the caudate-putamen cross-sectional area decreased (Spearman, P hydrocephalus is complex and is not solely dependent on brain tissue deformation. Further studies on the interactions between brain tissue stiffness, deformation, tissue oedema and neural damage are necessary before MRE can be used as a tool to track changes in brain biomechanics in hydrocephalus.

  10. BAG3 regulates contractility and Ca2+ homeostasis in adult mouse ventricular myocytes

    OpenAIRE

    Feldman, Arthur M.; Gordon, Jennifer; Wang, JuFang; Song, Jianliang; Zhang, Xue-Qian; Myers, Valerie D.; Tilley, Douglas G.; Gao, Erhe; Hoffman, Nicholas E.; Tomar, Dhanendra; Madesh, Muniswamy; Rabinowitz, Joseph; Koch, Walter J.; Su, Feifei; Khalili, Kamel

    2016-01-01

    Bcl2-associated athanogene 3 (BAG3) is a 575 amino acid anti-apoptotic protein that is constitutively expressed in the heart. BAG3 mutations, including mutations leading to loss of protein, are associated with familial cardiomyopathy. Furthermore, BAG3 levels have been found to be reduced in end-stage non-familial failing myocardium. In contrast to neonatal myocytes in which BAG3 is found in the cytoplasm and involved in protein quality control and apoptosis, in adult mouse left ventricular (...

  11. Influence of iron on plutonium absorption by the adult and neonatal rat

    International Nuclear Information System (INIS)

    Sullivan, M.F.; Ruemmler, P.S.; Buschbom, R.L.

    1986-01-01

    To determine how iron affects plutonium absorption, adult rats were gavaged with 238 Pu nitrate (pH 2) after they had been fed an iron-deficient diet or treated with iron supplements. Neonatal rats born to dams on an iron-deficient diet were also gavaged with 238 Pu. An iron-deficient diet resulted in enhanced 238 Pu absorption both in the adults and in neonates born to iron-deficient dams. Ferric iron increased 238 Pu absorption 12-fold in adult rats; injected iron-dextran reduced that increase; gavaged ferrous iron reduced 238 Pu absorption to one-third of the control value. Rat neonates absorbed 30 to 40 times as much 238 Pu as adults; absorption was lowered in groups that received iron supplements: Iron-dextran caused a 50% reduction; ferric iron, 95%; and ferrous iron, greater than 95%. The results demonstrate an effect of the oxidation state of iron on plutonium absorption in adult rats different from that observed in suckling rats. The results suggest that the high rate of 238 Pu absorption by neonatal animals is due not only to the permeability of their intestines but also to their high demand for iron

  12. Maternal exposure to cadmium during gestation perturbs the vascular system of the adult rat offspring

    International Nuclear Information System (INIS)

    Ronco, Ana Maria; Montenegro, Marcela; Castillo, Paula; Urrutia, Manuel; Saez, Daniel; Hirsch, Sandra; Zepeda, Ramiro; Llanos, Miguel N.

    2011-01-01

    Several cardiovascular diseases (CVD) observed in adulthood have been associated with environmental influences during fetal growth. Here, we show that maternal exposure to cadmium, a ubiquitously distributed heavy metal and main component of cigarette smoke is able to induce cardiovascular morpho-functional changes in the offspring at adult age. Heart morphology and vascular reactivity were evaluated in the adult offspring of rats exposed to 30 ppm of cadmium during pregnancy. Echocardiographic examination shows altered heart morphology characterized by a concentric left ventricular hypertrophy. Also, we observed a reduced endothelium-dependent reactivity in isolated aortic rings of adult offspring, while endothelium-independent reactivity remained unaltered. These effects were associated with an increase of hem-oxygenase 1 (HO-1) expression in the aortas of adult offspring. The expression of HO-1 was higher in females than males, a finding likely related to the sex-dependent expression of the vascular cell adhesion molecule 1 (VCAM-1), which was lower in the adult female. All these long-term consequences were observed along with normal birth weights and absence of detectable levels of cadmium in fetal and adult tissues of the offspring. In placental tissues however, cadmium levels were detected and correlated with increased NF-κB expression - a transcription factor sensitive to inflammation and oxidative stress - suggesting a placentary mechanism that affect genes related to the development of the cardiovascular system. Our results provide, for the first time, direct experimental evidence supporting that exposure to cadmium during pregnancy reprograms cardiovascular development of the offspring which in turn may conduce to a long term increased risk of CVD.

  13. Effect of trimetazidine treatment on the transient outward potassium current of the left ventricular myocytes of rats with streptozotocin-induced type 1 diabetes mellitus

    Energy Technology Data Exchange (ETDEWEB)

    Xiang, Yu-luan; He, Li [Department of Cardiology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing (China); Xiao, Jun [Department of Cardiology, Chongqing Emergency Medical Center, Chongqing (China); Xia, Shuang; Deng, Song-bai [Department of Cardiology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing (China); Xiu, Yun [Institute of Life Science, Chongqing Medical University, Chongqing (China); She, Qiang [Department of Cardiology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing (China)

    2012-02-17

    Cardiovascular complications are a leading cause of mortality in patients with diabetes mellitus (DM). The present study was designed to investigate the effects of trimetazidine (TMZ), an anti-angina drug, on transient outward potassium current (I{sub to}) remodeling in ventricular myocytes and the plasma contents of free fatty acid (FFA) and glucose in DM. Sprague-Dawley rats, 8 weeks old and weighing 200-250 g, were randomly divided into three groups of 20 animals each. The control group was injected with vehicle (1 mM citrate buffer), the DM group was injected with 65 mg/kg streptozotocin (STZ) for induction of type 1 DM, and the DM+TMZ group was injected with the same dose of STZ followed by a 4-week treatment with TMZ (60 mg·kg{sup −1}·day{sup −1}). All animals were then euthanized and their hearts excised and subjected to electrophysiological measurements or gene expression analyses. TMZ exposure significantly reversed the increased plasma FFA level in diabetic rats, but failed to change the plasma glucose level. The amplitude of I{sub to} was significantly decreased in left ventricular myocytes from diabetic rats relative to control animals (6.25 ± 1.45 vs 20.72 ± 2.93 pA/pF at +40 mV). The DM-associated I{sub to} reduction was attenuated by TMZ. Moreover, TMZ treatment reversed the increased expression of the channel-forming alpha subunit Kv1.4 and the decreased expression of Kv4.2 and Kv4.3 in diabetic rat hearts. These data demonstrate that TMZ can normalize, or partially normalize, the increased plasma FFA content, the reduced I{sub to} of ventricular myocytes, and the altered expression Kv1.4, Kv4.2, and Kv4.3 in type 1 DM.

  14. Effect of trimetazidine treatment on the transient outward potassium current of the left ventricular myocytes of rats with streptozotocin-induced type 1 diabetes mellitus

    International Nuclear Information System (INIS)

    Xiang, Yu-luan; He, Li; Xiao, Jun; Xia, Shuang; Deng, Song-bai; Xiu, Yun; She, Qiang

    2012-01-01

    Cardiovascular complications are a leading cause of mortality in patients with diabetes mellitus (DM). The present study was designed to investigate the effects of trimetazidine (TMZ), an anti-angina drug, on transient outward potassium current (I to ) remodeling in ventricular myocytes and the plasma contents of free fatty acid (FFA) and glucose in DM. Sprague-Dawley rats, 8 weeks old and weighing 200-250 g, were randomly divided into three groups of 20 animals each. The control group was injected with vehicle (1 mM citrate buffer), the DM group was injected with 65 mg/kg streptozotocin (STZ) for induction of type 1 DM, and the DM+TMZ group was injected with the same dose of STZ followed by a 4-week treatment with TMZ (60 mg·kg −1 ·day −1 ). All animals were then euthanized and their hearts excised and subjected to electrophysiological measurements or gene expression analyses. TMZ exposure significantly reversed the increased plasma FFA level in diabetic rats, but failed to change the plasma glucose level. The amplitude of I to was significantly decreased in left ventricular myocytes from diabetic rats relative to control animals (6.25 ± 1.45 vs 20.72 ± 2.93 pA/pF at +40 mV). The DM-associated I to reduction was attenuated by TMZ. Moreover, TMZ treatment reversed the increased expression of the channel-forming alpha subunit Kv1.4 and the decreased expression of Kv4.2 and Kv4.3 in diabetic rat hearts. These data demonstrate that TMZ can normalize, or partially normalize, the increased plasma FFA content, the reduced I to of ventricular myocytes, and the altered expression Kv1.4, Kv4.2, and Kv4.3 in type 1 DM

  15. Effect of exercise training on Ca2+ release units of left ventricular myocytes of spontaneously hypertensive rats.

    Science.gov (United States)

    Carneiro-Júnior, M A; Quintão-Júnior, J F; Drummond, L R; Lavorato, V N; Drummond, F R; Amadeu, M A; Oliveira, E M; Felix, L B; Cruz, J S; Mill, J G; Natali, A J; Prímola-Gomes, T N

    2014-08-29

    In cardiomyocytes, calcium (Ca2+) release units comprise clusters of intracellular Ca2+ release channels located on the sarcoplasmic reticulum, and hypertension is well established as a cause of defects in calcium release unit function. Our objective was to determine whether endurance exercise training could attenuate the deleterious effects of hypertension on calcium release unit components and Ca2+ sparks in left ventricular myocytes of spontaneously hypertensive rats. Male Wistar and spontaneously hypertensive rats (4 months of age) were divided into 4 groups: normotensive (NC) and hypertensive control (HC), and normotensive (NT) and hypertensive trained (HT) animals (7 rats per group). NC and HC rats were submitted to a low-intensity treadmill running protocol (5 days/week, 1 h/day, 0% grade, and 50-60% of maximal running speed) for 8 weeks. Gene expression of the ryanodine receptor type 2 (RyR2) and FK506 binding protein (FKBP12.6) increased (270%) and decreased (88%), respectively, in HC compared to NC rats. Endurance exercise training reversed these changes by reducing RyR2 (230%) and normalizing FKBP12.6 gene expression (112%). Hypertension also increased the frequency of Ca2+ sparks (HC=7.61±0.26 vs NC=4.79±0.19 per 100 µm/s) and decreased its amplitude (HC=0.260±0.08 vs NC=0.324±0.10 ΔF/F0), full width at half-maximum amplitude (HC=1.05±0.08 vs NC=1.26±0.01 µm), total duration (HC=11.51±0.12 vs NC=14.97±0.24 ms), time to peak (HC=4.84±0.06 vs NC=6.31±0.14 ms), and time constant of decay (HC=8.68±0.12 vs NC=10.21±0.22 ms). These changes were partially reversed in HT rats (frequency of Ca2+ sparks=6.26±0.19 µm/s, amplitude=0.282±0.10 ΔF/F0, full width at half-maximum amplitude=1.14±0.01 µm, total duration=13.34±0.17 ms, time to peak=5.43±0.08 ms, and time constant of decay=9.43±0.15 ms). Endurance exercise training attenuated the deleterious effects of hypertension on calcium release units of left ventricular myocytes.

  16. Effect of exercise training on Ca2+ release units of left ventricular myocytes of spontaneously hypertensive rats

    Directory of Open Access Journals (Sweden)

    M.A. Carneiro-Júnior

    2014-11-01

    Full Text Available In cardiomyocytes, calcium (Ca2+ release units comprise clusters of intracellular Ca2+ release channels located on the sarcoplasmic reticulum, and hypertension is well established as a cause of defects in calcium release unit function. Our objective was to determine whether endurance exercise training could attenuate the deleterious effects of hypertension on calcium release unit components and Ca2+ sparks in left ventricular myocytes of spontaneously hypertensive rats. Male Wistar and spontaneously hypertensive rats (4 months of age were divided into 4 groups: normotensive (NC and hypertensive control (HC, and normotensive (NT and hypertensive trained (HT animals (7 rats per group. NC and HC rats were submitted to a low-intensity treadmill running protocol (5 days/week, 1 h/day, 0% grade, and 50-60% of maximal running speed for 8 weeks. Gene expression of the ryanodine receptor type 2 (RyR2 and FK506 binding protein (FKBP12.6 increased (270% and decreased (88%, respectively, in HC compared to NC rats. Endurance exercise training reversed these changes by reducing RyR2 (230% and normalizing FKBP12.6 gene expression (112%. Hypertension also increased the frequency of Ca2+ sparks (HC=7.61±0.26 vs NC=4.79±0.19 per 100 µm/s and decreased its amplitude (HC=0.260±0.08 vs NC=0.324±0.10 ΔF/F0, full width at half-maximum amplitude (HC=1.05±0.08 vs NC=1.26±0.01 µm, total duration (HC=11.51±0.12 vs NC=14.97±0.24 ms, time to peak (HC=4.84±0.06 vs NC=6.31±0.14 ms, and time constant of decay (HC=8.68±0.12 vs NC=10.21±0.22 ms. These changes were partially reversed in HT rats (frequency of Ca2+ sparks=6.26±0.19 µm/s, amplitude=0.282±0.10 ΔF/F0, full width at half-maximum amplitude=1.14±0.01 µm, total duration=13.34±0.17 ms, time to peak=5.43±0.08 ms, and time constant of decay=9.43±0.15 ms. Endurance exercise training attenuated the deleterious effects of hypertension on calcium release units of left ventricular myocytes.

  17. Effect of exercise training on Ca2+ release units of left ventricular myocytes of spontaneously hypertensive rats

    International Nuclear Information System (INIS)

    Carneiro-Júnior, M.A.; Quintão-Júnior, J.F.; Drummond, L.R.; Lavorato, V.N.; Drummond, F.R.; Amadeu, M.A.; Oliveira, E.M.; Felix, L.B.; Cruz, J.S.; Mill, J.G.; Natali, A.J.; Prímola-Gomes, T.N.

    2014-01-01

    In cardiomyocytes, calcium (Ca 2+ ) release units comprise clusters of intracellular Ca 2+ release channels located on the sarcoplasmic reticulum, and hypertension is well established as a cause of defects in calcium release unit function. Our objective was to determine whether endurance exercise training could attenuate the deleterious effects of hypertension on calcium release unit components and Ca 2+ sparks in left ventricular myocytes of spontaneously hypertensive rats. Male Wistar and spontaneously hypertensive rats (4 months of age) were divided into 4 groups: normotensive (NC) and hypertensive control (HC), and normotensive (NT) and hypertensive trained (HT) animals (7 rats per group). NC and HC rats were submitted to a low-intensity treadmill running protocol (5 days/week, 1 h/day, 0% grade, and 50-60% of maximal running speed) for 8 weeks. Gene expression of the ryanodine receptor type 2 (RyR2) and FK506 binding protein (FKBP12.6) increased (270%) and decreased (88%), respectively, in HC compared to NC rats. Endurance exercise training reversed these changes by reducing RyR2 (230%) and normalizing FKBP12.6 gene expression (112%). Hypertension also increased the frequency of Ca 2+ sparks (HC=7.61±0.26 vs NC=4.79±0.19 per 100 µm/s) and decreased its amplitude (HC=0.260±0.08 vs NC=0.324±0.10 ΔF/F 0 ), full width at half-maximum amplitude (HC=1.05±0.08 vs NC=1.26±0.01 µm), total duration (HC=11.51±0.12 vs NC=14.97±0.24 ms), time to peak (HC=4.84±0.06 vs NC=6.31±0.14 ms), and time constant of decay (HC=8.68±0.12 vs NC=10.21±0.22 ms). These changes were partially reversed in HT rats (frequency of Ca 2+ sparks=6.26±0.19 µm/s, amplitude=0.282±0.10 ΔF/F 0 , full width at half-maximum amplitude=1.14±0.01 µm, total duration=13.34±0.17 ms, time to peak=5.43±0.08 ms, and time constant of decay=9.43±0.15 ms). Endurance exercise training attenuated the deleterious effects of hypertension on calcium release units of left ventricular myocytes

  18. The inotropic effect of the active metabolite of levosimendan, OR-1896, is mediated through inhibition of PDE3 in rat ventricular myocardium.

    Directory of Open Access Journals (Sweden)

    Øivind Ørstavik

    Full Text Available We recently published that the positive inotropic response (PIR to levosimendan can be fully accounted for by phosphodiesterase (PDE inhibition in both failing human heart and normal rat heart. To determine if the PIR of the active metabolite OR-1896, an important mediator of the long-term clinical effects of levosimendan, also results from PDE3 inhibition, we compared the effects of OR-1896, a representative Ca2+ sensitizer EMD57033 (EMD, levosimendan and other PDE inhibitors.Contractile force was measured in rat ventricular strips. PDE assay was conducted on rat ventricular homogenate. cAMP was measured using RII_epac FRET-based sensors.OR-1896 evoked a maximum PIR of 33 ± 10% above basal at 1 μM. This response was amplified in the presence of the PDE4 inhibitor rolipram (89 ± 14% and absent in the presence of the PDE3 inhibitors cilostamide (0.5 ± 5.3% or milrinone (3.2 ± 4.4%. The PIR was accompanied by a lusitropic response, and both were reversed by muscarinic receptor stimulation with carbachol and absent in the presence of β-AR blockade with timolol. OR-1896 inhibited PDE activity and increased cAMP levels at concentrations giving PIRs. OR-1896 did not sensitize the concentration-response relationship to extracellular Ca2+. Levosimendan, OR-1896 and EMD all increased the sensitivity to β-AR stimulation. The combination of either EMD and levosimendan or EMD and OR-1896 further sensitized the response, indicating at least two different mechanisms responsible for the sensitization. Only EMD sensitized the α1-AR response.The observed PIR to OR-1896 in rat ventricular strips is mediated through PDE3 inhibition, enhancing cAMP-mediated effects. These results further reinforce our previous finding that Ca2+ sensitization does not play a significant role in the inotropic (and lusitropic effect of levosimendan, nor of its main metabolite OR-1896.

  19. Intracellular [Ca2+] and Vo2 after manipulation of the free-energy of the Na+/Ca(2+)-exchanger in isolated rat ventricular myocytes

    NARCIS (Netherlands)

    Fiolet, J. W.; Baartscheer, A.; Schumacher, C. A.

    1995-01-01

    We have investigated whether the Na+/Ca(2+)-exchanger has a functional regulatory role in the control of oxidative metabolism in suspensions of isolated rat ventricular myocytes. Therefore we simultaneously measured intracellular [Ca2+] ([Ca2+]i) with Indo-1 and respiratory rate (Vo2) after abrupt

  20. Left Ventricular Geometry In Nigerians With Type II Diabetes Mellitus ...

    African Journals Online (AJOL)

    Background: Left ventricular hypertrophy is independently associated with increased incidence of cardiovascular disease, cardiovascular and all cause mortality. In a relatively healthy hypertensive adult population, type II diabetes is associated with higher left ventricular mass, concentric left ventricular geometry and lower ...

  1. [Subcutaneous transplants of juvenile rat testicular tissues continue to develop and secret androgen in adult rats].

    Science.gov (United States)

    Yu, Zhou; Wang, Tong; Cui, Jiangbo; Song, Yajuan; Ma, Xianjie; Su, Yingjun; Peng, Pai

    2017-12-01

    Objective To explore the effects of subcutaneous microenvironment of adult rats on survival, development and androgen secretion of Leydig cells of transplanted juvenile rat testis. Methods Healthy adult SD rats were randomly divided into control group, sham group, castrated group and non-castrated group. Rats in the control group were kept intact, no testis was transplanted subcutaneously after adult recipients were castrated in the sham group; 5-7-day juvenile rat testes were transplanted subcutaneously in the castrated group, with one testis per side; Testes resected from juvenile rats were directly transplanted subcutaneously on both sides of the recipients in the non-castrated group. The grafts were obtained and weighed 4 weeks later. Then the histological features of the grafts were examined by HE staining; the expression and distribution of hydroxysteroid 17-beta dehydrogenase 1 (HSD-17β1) were investigated by immunohistochemistry; and the serum androgen level was determined by ELISA. Results The average mass of grafts obtained from the castrated group was significantly higher than that of the non-castrated group. Immunohistochemistry indicated that Leydig cells were visible in the tissues from both the castrated and non-castrated groups, but the number of HSD-17β1-posotive cells in the castrated group was larger than that in the non-castrated group. ELISA results showed that the serum androgen level was higher in the control group and non-castrated group than in the sham group and castrated group, and compared with the sham group, the serum androgen level in the castrated group was significantly higher. Conclusion The juvenile rat testis subcutaneously transplanted could further develop under the adult recipient rat skin, and the Leydig cells of grafts harbored the ability to produce and secret androgen.

  2. Alpha1A-adrenergic receptor-directed autoimmunity induces left ventricular damage and diastolic dysfunction in rats.

    Directory of Open Access Journals (Sweden)

    Katrin Wenzel

    Full Text Available BACKGROUND: Agonistic autoantibodies to the alpha(1-adrenergic receptor occur in nearly half of patients with refractory hypertension; however, their relevance is uncertain. METHODS/PRINCIPAL FINDINGS: We immunized Lewis rats with the second extracellular-loop peptides of the human alpha(1A-adrenergic receptor and maintained them for one year. Alpha(1A-adrenergic antibodies (alpha(1A-AR-AB were monitored with a neonatal cardiomyocyte contraction assay by ELISA, and by ERK1/2 phosphorylation in human alpha(1A-adrenergic receptor transfected Chinese hamster ovary cells. The rats were followed with radiotelemetric blood pressure measurements and echocardiography. At 12 months, the left ventricles of immunized rats had greater wall thickness than control rats. The fractional shortening and dp/dt(max demonstrated preserved systolic function. A decreased E/A ratio in immunized rats indicated a diastolic dysfunction. Invasive hemodynamics revealed increased left ventricular end-diastolic pressures and decreased dp/dt(min. Mean diameter of cardiomyocytes showed hypertrophy in immunized rats. Long-term blood pressure values and heart rates were not different. Genes encoding sarcomeric proteins, collagens, extracellular matrix proteins, calcium regulating proteins, and proteins of energy metabolism in immunized rat hearts were upregulated, compared to controls. Furthermore, fibrosis was present in immunized hearts, but not in control hearts. A subset of immunized and control rats was infused with angiotensin (Ang II. The stressor raised blood pressure to a greater degree and led to more cardiac fibrosis in immunized, than in control rats. CONCLUSIONS/SIGNIFICANCE: We show that alpha(1A-AR-AB cause diastolic dysfunction independent of hypertension, and can increase the sensitivity to Ang II. We suggest that alpha(1A-AR-AB could contribute to cardiovascular endorgan damage.

  3. Right ventricular pressure elevated in one-kidney, one clip Goldblatt hypertensive rats.

    Science.gov (United States)

    Ketabchi, Farzaneh; Bajoovand, Shirin; Adlband, Mojtaba; Naseh, Maryam; Nekooeian, Ali A; Mashghoolozekr, Elaheh

    2017-01-01

    Both renal and respiratory diseases are common with high mortality rate around the world. This study was the first to compare effects of two kidneys, one clip (2K1C) and one-kidney, one clip (1K1C) Goldblatt hypertension on right ventricular pressure during normal condition and mechanical ventilation with hypoxia gas. Male Sprague-Dawley rats were subjected to control, 2K1C, or 1K1C groups. Twenty-eight days after the first surgery, animals were anesthetized, and femoral artery and vein, and right ventricle cannulated. Systemic arterial pressure and right ventricular systolic pressures (RVSP) were recorded during ventilation the animals with normoxic or hypoxic gas. RVSP in the 1K1C group was significantly more than the control and 2K1C groups during baseline conditions and ventilation the animals with hypoxic gas. Administration of antioxidant Trolox increased RVSP in the 1K1C and control groups compared with their baselines. Furthermore, there was no alteration in RVSP during hypoxia in the presence of Trolox. This study indicated that RVSP only increased after 28 days induction of 1K1C but not 2K1C model. In addition, it seems that the response to hypoxic gas and antioxidants in 1K1C is more than 2K1C. These data also suggest that effects of 1K1C may partially be related to reactive oxygen species (ROS) pathways.

  4. In vitro uptake of 75Se-selenite by lens of young and adult rats

    International Nuclear Information System (INIS)

    Sladkova, J.; Ostadalova, I.; Babicky, A.; Obenberger, J.

    1988-01-01

    The uptake was observed of 75 Se-selenite by the lens in Wistar strain rats in adult animals, in 17-day old rats kept with their mothers and in prematurely weaned rats. Also measured was the excretion of 75 Se by the lens of young and adult rats following incubation in the medium with radioselenium. The metabolites were analysed which were discharged by the lens containing 75 Se. In Brattleboro rats the uptake of 75 Se-selenite was also measured by the lens in young and adult rats. The uptake of 75 Se-selenite by the lens in young Wistar rats was found to be 1.6 times higher than by the lens of adult rats and the time course of the radioselenium uptake was slightly different. In the lens of prematurely weaned rats no significant difference was found in the uptake of radioselenium after 4 hours as compared with rats of the same age kept with their mothers. In homozygous Brattleboro rats, a higher uptake of 75 Se-selenite was found as compared with both young and adult heterozygous rats. The time course and the quantity of 75 Se efflux from the lens of young and adult Wistar rats differed significantly after 0.5 hour of pre-incubation. From metabolites containing 75 Se excreted by the lens following preincubation, glutathione selenotrisulfide and a not yet accurately determined fraction with a large share of radioactivity were isolated. The stated results provide yet more proof that selenium cataract is a manifestation of the ontogenic dependence of selenium metabolism in the lens and in the entire organism. (author). 4 tabs., 30 refs

  5. Radiation-induced apoptosis in the neonatal and adult rat spinal cord.

    Science.gov (United States)

    Li, Y Q; Wong, C S

    2000-09-01

    This study was designed to characterize radiation-induced apoptosis in the spinal cord of the neonatal and young adult rat. Spinal cords (C2-T2) of 1-, 2- and 10-week-old rats were irradiated with a single dose of 8, 18 or 22 Gy. Apoptosis was assessed histologically according to its specific morphological features or by using the TUNEL assay. Cell proliferation was assessed immunohistochemically using BrdU. Identities of cell types undergoing apoptosis were assessed using immunohistochemistry or in situ hybridization using markers for neurons, glial progenitor cells, microglia, oligodendrocytes and astrocytes. The time course of radiation-induced apoptosis in 1- or 2-week-old rat spinal cord was similar to that in the young adult rat spinal cord. A peak response was observed at about 8 h after irradiation, and the apoptosis index returned to the levels in nonirradiated spinal cords at 24 h. The neonatal rat spinal cord demonstrated increased apoptosis compared to the adult. Values for total yield of apoptosis over 24 h induced by 8 Gy in the neonatal rat spinal cord were significantly greater than that in the adult. Immunohistochemistry studies using Leu7, galactocerebroside, Rip and adenomatous polyposis coli tumor suppressor protein indicated that most apoptotic cells were cells of the oligodendroglial lineage regardless of the age of the animal. No evidence of Gfap or factor VIII-related antigen-positive apoptotic cells was observed, and there was a small number of apoptotic microglial cells (lectin-Rca1 positive) in the neonatal and adult rat spinal cord. In the neonatal but not adult rat spinal cord, about 10% of the apoptotic cells appeared to be neurons and were immunoreactive for synaptophysin. Labeling indices (LI) for BrdU in nonirradiated 1- and 2-week-old rat spinal cord were 20.0 and 16.3%, respectively, significantly greater than the LI of 1.0% in the 10-week-old rat spinal cord. At 8 h after a single dose of 8 Gy, 13.4% of the apoptotic cells were

  6. Reduced Cerebral Oxygen Content in the DG and SVZ In Situ Promotes Neurogenesis in the Adult Rat Brain In Vivo.

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    Kuan Zhang

    Full Text Available Neurogenesis in the adult brain occurs mainly within two neurogenic structures, the dentate gyrus (DG of the hippocampus and the sub-ventricular zone (SVZ of the forebrain. It has been reported that mild hypoxia promoted the proliferation of Neural Stem Cells (NSCsin vitro. Our previous study further demonstrated that an external hypoxic environment stimulated neurogenesis in the adult rat brain in vivo. However, it remains unknown how external hypoxic environments affect the oxygen content in the brain and result in neurogenesis. Here we use an optical fiber luminescent oxygen sensor to detect the oxygen content in the adult rat brain in situ under normoxia and hypoxia. We found that the distribution of oxygen in cerebral regions is spatiotemporally heterogeneous. The Po2 values in the ventricles (45∼50 Torr and DG (approximately 10 Torr were much higher than those of other parts of the brain, such as the cortex and thalamus (approximately 2 Torr. Interestingly, our in vivo studies showed that an external hypoxic environment could change the intrinsic oxygen content in brain tissues, notably reducing oxygen levels in both the DG and SVZ, the major sites of adult neurogenesis. Furthermore, the hypoxic environment also increased the expression of HIF-1α and VEGF, two factors that have been reported to regulate neurogenesis, within the DG and SVZ. Thus, we have demonstrated that reducing the oxygen content of the external environment decreased Po2 levels in the DG and SVZ. This reduced oxygen level in the DG and SVZ might be the main mechanism triggering neurogenesis in the adult brain. More importantly, we speculate that varying oxygen levels may be the physiological basis of the regionally restricted neurogenesis in the adult brain.

  7. Computerized tomography in diagnosing cerebral atrophy (measurements of the ventricular system and hemispheric sulci in healthy adults)

    International Nuclear Information System (INIS)

    Taneva, N.

    1996-01-01

    Brain atrophy problem faced in healthy adults and in patients with a variety of diseases is disputable in the literature. An important issue of interpretation of CT-results is the criterion of normal values of the ventricular system and sulci. The results obtained in this investigation of forty healthy adults help to establish the values in norm and pathology. The data are compared with those reported by other authors. A number of characteristic features, attributable to gender and age, are noted. 10 refs., 2 tabs., 2 figs. (author)

  8. Effect of Losartan on Right Ventricular Dysfunction: Results From the Double-Blind, Randomized REDEFINE Trial (Right Ventricular Dysfunction in Tetralogy of Fallot: Inhibition of the Renin-Angiotensin-Aldosterone System) in Adults With Repaired Tetralogy of Fallot.

    Science.gov (United States)

    Bokma, Jouke P; Winter, Michiel M; van Dijk, Arie P; Vliegen, Hubert W; van Melle, Joost P; Meijboom, Folkert J; Post, Martijn C; Berbee, Jacqueline K; Boekholdt, S Matthijs; Groenink, Maarten; Zwinderman, Aeilko H; Mulder, Barbara J M; Bouma, Berto J

    2018-04-03

    The effect of angiotensin II receptor blockers on right ventricular (RV) function is still unknown. Angiotensin II receptor blockers are beneficial in patients with acquired left ventricular dysfunction, and recent findings have suggested a favorable effect in symptomatic patients with systemic RV dysfunction. The current study aimed to determine the effect of losartan, an angiotensin II receptor blocker, on subpulmonary RV dysfunction in adults after repaired tetralogy of Fallot. The REDEFINE trial (Right Ventricular Dysfunction in Tetralogy of Fallot: Inhibition of the Renin-Angiotensin-Aldosterone System) is an investigator-initiated, multicenter, prospective, 1:1 randomized, double-blind, placebo-controlled study. Adults with repaired tetralogy of Fallot and RV dysfunction (RV ejection fraction [EF] 0.30 for all). In predefined subgroup analyses, losartan did not have a statistically significant impact on RV EF in subgroups with symptoms, restrictive RV, RV EFtetralogy of Fallot. Future larger studies may determine whether there might be a role for losartan in specific vulnerable subgroups. URL: https://www.clinicaltrials.gov. Unique identifier: NCT02010905. © 2017 American Heart Association, Inc.

  9. Situs inversus totalis associated with subaortic stenosis, restrictive ventricular septal defect, and tricuspid dysplasia in an adult dog.

    Science.gov (United States)

    Piantedosi, Diego; Cortese, Laura; Meomartino, Leonardo; Di Loria, Antonio; Ciaramella, Paolo

    2011-11-01

    A rare association between situs inversus totalis (SIT), restrictive ventricular septal defect, severe subaortic stenosis, and tricuspid dysplasia was observed in an adult mixed-breed dog. Primary ciliary dyskinesia and Kartagener's syndrome were excluded. After 15 mo the dog died suddenly. The association between SIT and congenital heart diseases is discussed.

  10. Effect of exercise training on Ca{sup 2+} release units of left ventricular myocytes of spontaneously hypertensive rats

    Energy Technology Data Exchange (ETDEWEB)

    Carneiro-Júnior, M.A. [Universidade Federal do Espírito Santo, Departamento de Ciências Fisiológicas, Vitória, ES (Brazil); Universidade Federal de Viçosa, Laboratório de Biologia do Exercício, Departamento de Educação Física, Viçosa, MG (Brazil); Quintão-Júnior, J.F.; Drummond, L.R.; Lavorato, V.N.; Drummond, F.R. [Universidade Federal de Viçosa, Laboratório de Biologia do Exercício, Departamento de Educação Física, Viçosa, MG (Brazil); Amadeu, M.A.; Oliveira, E.M. [Universidade de São Paulo, Laboratório de Bioquímica e Biologia Molecular do Exercício, Escola de Educação Física e Esportes, São Paulo, SP (Brazil); Felix, L.B. [Universidade Federal de Viçosa, Departamento de Engenharia Elétrica, Viçosa, MG (Brazil); Cruz, J.S. [Universidade Federal de Minas Gerais, Laboratório de Membranas Excitáveis e Biologia Cardiovascular, Departamento de Bioquímica e Imunologia, Belo Horizonte, MG (Brazil); Mill, J.G. [Universidade Federal do Espírito Santo, Departamento de Ciências Fisiológicas, Vitória, ES (Brazil); Natali, A.J.; Prímola-Gomes, T.N. [Universidade Federal de Viçosa, Laboratório de Biologia do Exercício, Departamento de Educação Física, Viçosa, MG (Brazil)

    2014-08-29

    In cardiomyocytes, calcium (Ca{sup 2+}) release units comprise clusters of intracellular Ca{sup 2+} release channels located on the sarcoplasmic reticulum, and hypertension is well established as a cause of defects in calcium release unit function. Our objective was to determine whether endurance exercise training could attenuate the deleterious effects of hypertension on calcium release unit components and Ca{sup 2+} sparks in left ventricular myocytes of spontaneously hypertensive rats. Male Wistar and spontaneously hypertensive rats (4 months of age) were divided into 4 groups: normotensive (NC) and hypertensive control (HC), and normotensive (NT) and hypertensive trained (HT) animals (7 rats per group). NC and HC rats were submitted to a low-intensity treadmill running protocol (5 days/week, 1 h/day, 0% grade, and 50-60% of maximal running speed) for 8 weeks. Gene expression of the ryanodine receptor type 2 (RyR2) and FK506 binding protein (FKBP12.6) increased (270%) and decreased (88%), respectively, in HC compared to NC rats. Endurance exercise training reversed these changes by reducing RyR2 (230%) and normalizing FKBP12.6 gene expression (112%). Hypertension also increased the frequency of Ca{sup 2+} sparks (HC=7.61±0.26 vs NC=4.79±0.19 per 100 µm/s) and decreased its amplitude (HC=0.260±0.08 vs NC=0.324±0.10 ΔF/F{sub 0}), full width at half-maximum amplitude (HC=1.05±0.08 vs NC=1.26±0.01 µm), total duration (HC=11.51±0.12 vs NC=14.97±0.24 ms), time to peak (HC=4.84±0.06 vs NC=6.31±0.14 ms), and time constant of decay (HC=8.68±0.12 vs NC=10.21±0.22 ms). These changes were partially reversed in HT rats (frequency of Ca{sup 2+} sparks=6.26±0.19 µm/s, amplitude=0.282±0.10 ΔF/F{sub 0}, full width at half-maximum amplitude=1.14±0.01 µm, total duration=13.34±0.17 ms, time to peak=5.43±0.08 ms, and time constant of decay=9.43±0.15 ms). Endurance exercise training attenuated the deleterious effects of hypertension on calcium release units of

  11. A novel hydrodynamic approach of drag-reducing polymers to improve left ventricular hypertrophy and aortic remodeling in spontaneously hypertensive rats

    Directory of Open Access Journals (Sweden)

    Zhang X

    2016-12-01

    Full Text Available Xinlu Zhang,1,* Xu Wang,2,* Feng Hu,1 Boda Zhou,3 Hai-Bin Chen,1 Daogang Zha,1 Yili Liu,1 Yansong Guo,4 Lemin Zheng,2 Jiancheng Xiu1 1Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, 2The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, and Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, Peking University Health Science Center, 3Department of Cardiology, Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, and Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides of Ministry of Health, Peking University Third Hospital, Beijing, 4Department of Cardiovascular Medicine, Fujian Provincial Hospital, Fuzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Drag-reducing polymers (DRPs, when added in minute concentrations, have been shown to decrease peripheral vascular resistance. In this study, the effect of DRPs on the hypertension-induced left ventricular hypertrophy and aortic remodeling was evaluated in spontaneously hypertensive rats (SHR. Male SHR and age-matched Wistar rats were divided into four groups and received intravenous injection of normal saline (NS or DRPs. Body weight (BW, heart rate (HR and systolic blood pressure (SBP were measured. Echocardiography was used to evaluate the changes in left ventricle (LV function and global wall motion. The LV and aorta were stained by hematoxylin and eosin. Cell size of cardiomyocytes and aortic medial thickness were evaluated for each section. The expression of endothelin-1 (ET-1 of LV and aorta was examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR and immunohistochemistry. There was no significant difference in the increase of SBP among SHR + NS, SHR + 10DRP and SHR + 20DRP groups. SHR + NS group had markedly smaller left ventricular end

  12. High affinity [3H]glibenclamide binding sites in rat neuronal and cardiac tissue: Localization and developmental characteristics

    International Nuclear Information System (INIS)

    Miller, J.A.; Velayo, N.L.; Dage, R.C.; Rampe, D.

    1991-01-01

    We examined the binding of the antidiabetic sulfonylurea [3H] glibenclamide to rat brain and heart membranes. High affinity binding was observed in adult rat forebrain (Kd = 137.3 pM, maximal binding site density = 91.8 fmol/mg of protein) and ventricle (Kd = 77.1 pM, maximal binding site density = 65.1 fmol/mg of protein). Binding site density increased approximately 250% in forebrain membranes during postnatal development but was constant in ventricular membranes. Quantitative autoradiography was used to examine the regional distribution of [3H] glibenclamide binding sites in sections from rat brain, spinal cord and heart. The greatest density of binding in adult brain was found in the substantia nigra and globus pallidus, whereas the other areas displayed heterogenous binding. In agreement with the membrane binding studies, 1-day-old rat brain had significantly fewer [3H]glibenclamide binding sites than adult brain. Additionally, the pattern of distribution of these sites was qualitatively different from that of the adult. In adult rat spinal cord, moderate binding densities were observed in spinal cord gray and displayed a rostral to caudal gradient. In adult rat heart, moderate binding densities were observed and the sites were distributed homogeneously. In conclusion, significant development of [3H]glibenclamide binding sites was seen in the brain but not the heart during postnatal maturation. Furthermore, a heterogeneous distribution of binding sites was observed in both the brain and spinal cord of adult rats

  13. Pharmacokinetics of bisphenol A in neonatal and adult Sprague-Dawley rats

    International Nuclear Information System (INIS)

    Doerge, Daniel R.; Twaddle, Nathan C.; Vanlandingham, Michelle; Fisher, Jeffrey W.

    2010-01-01

    Bisphenol A (BPA) is an important industrial chemical used in the manufacture of polycarbonate plastic products and epoxy resin-based food can liners. The presence of BPA in urine of > 90% of Americans aged 6-60 suggests ubiquitous and frequent exposure. The current study used LC/MS/MS to measure serum pharmacokinetics of aglycone (active) and conjugated (inactive) BPA in adult and neonatal Sprague-Dawley rats by oral and injection routes. Deuterated BPA was used to avoid issues of background contamination. Linear pharmacokinetics were observed in adult rats treated orally in the range of 0-200 μg/kg bw. Evidence for enterohepatic recirculation of conjugated, but not aglycone, BPA was observed in adult rats. Significant inverse relationships were observed between postnatal age and measures of internal exposures to aglycone BPA and its elimination. In neonatal rats treated orally, internal exposures to aglycone BPA were substantially lower than from subcutaneous injection. The results reinforce the critical role for first-pass Phase II metabolism of BPA in gut and liver after oral exposure that attenuates internal exposure to the aglycone form in rats of all ages. The internal exposures to aglycone BPA observed in adult and neonatal rats following a single oral dose of 100 μg/kg bw are inconsistent with effects mediated by classical estrogen receptors based on binding affinities. However, an impact on alternative estrogen signaling pathways that have higher receptor affinity cannot be excluded in neonatal rats. These findings emphasize the importance of matching aglycone BPA internal dosimetry with receptor affinities in experimental animal studies reporting toxicity.

  14. Age-related ventricular-vascular coupling during acute inflammation in humans: Effect of physical activity.

    Science.gov (United States)

    Lane, Abbi D; Kappus, Rebecca M; Bunsawat, Kanokwan; Ranadive, Sushant M; Yan, Huimin; Phillips, Shane; Baynard, Tracy; Woods, Jeffrey A; Motl, Robert; Fernhall, Bo

    2015-07-01

    Aging is commonly accompanied by increased arterial and ventricular stiffness (determined by arterial elastance (Ea) and ventricular elastance (Elv)), augmented ventricular-vascular coupling ratios (Ea/Elv) and systemic inflammation. Acute inflammation may impact ventricular-vascular coupling and predispose older adults to cardiovascular events. However, physically active older adults have more compliant large arteries and left ventricles and lower inflammation than sedentary older adults. We hypothesized that acute inflammation would alter Ea, Elv, and Ea/Elv more in older versus younger adults but that higher levels of physical activity would attenuate inflammation-induced changes. End-systolic and central blood pressures were obtained using applanation tonometry before and at 24 and 48 h post-influenza vaccination in 24 older and 38 younger adults. Ultrasonography was used to measure ventricular volumes and other indices of cardiac performance. Physical activity was measured with accelerometry. Ea and Ea/Elv were maintained (p > 0.05), but Elv was reduced (p  0.05) except in the most active group of seniors (p < 0.05). Aging did not affect the elastance responses but did affect central blood pressure and other ventricular systolic responses to acute inflammation. Aging, not physical activity, appears to modulate cardiovascular responses to acute inflammation, except in the most active older adults. © The European Society of Cardiology 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  15. Situs inversus totalis associated with subaortic stenosis, restrictive ventricular septal defect, and tricuspid dysplasia in an adult dog

    OpenAIRE

    Piantedosi, Diego; Cortese, Laura; Meomartino, Leonardo; Di Loria, Antonio; Ciaramella, Paolo

    2011-01-01

    A rare association between situs inversus totalis (SIT), restrictive ventricular septal defect, severe subaortic stenosis, and tricuspid dysplasia was observed in an adult mixed-breed dog. Primary ciliary dyskinesia and Kartagener’s syndrome were excluded. After 15 mo the dog died suddenly. The association between SIT and congenital heart diseases is discussed.

  16. Atorvastatin Improves Ventricular Remodeling after Myocardial Infarction by Interfering with Collagen Metabolism

    Science.gov (United States)

    Reichert, Karla; Pereira do Carmo, Helison Rafael; Galluce Torina, Anali; Diógenes de Carvalho, Daniela; Carvalho Sposito, Andrei; de Souza Vilarinho, Karlos Alexandre; da Mota Silveira-Filho, Lindemberg; Martins de Oliveira, Pedro Paulo

    2016-01-01

    Purpose Therapeutic strategies that modulate ventricular remodeling can be useful after acute myocardial infarction (MI). In particular, statins may exert effects on molecular pathways involved in collagen metabolism. The aim of this study was to determine whether treatment with atorvastatin for 4 weeks would lead to changes in collagen metabolism and ventricular remodeling in a rat model of MI. Methods Male Wistar rats were used in this study. MI was induced in rats by ligation of the left anterior descending coronary artery (LAD). Animals were randomized into three groups, according to treatment: sham surgery without LAD ligation (sham group, n = 14), LAD ligation followed by 10mg atorvastatin/kg/day for 4 weeks (atorvastatin group, n = 24), or LAD ligation followed by saline solution for 4 weeks (control group, n = 27). After 4 weeks, hemodynamic characteristics were obtained by a pressure-volume catheter. Hearts were removed, and the left ventricles were subjected to histologic analysis of the extents of fibrosis and collagen deposition, as well as the myocyte cross-sectional area. Expression levels of mediators involved in collagen metabolism and inflammation were also assessed. Results End-diastolic volume, fibrotic content, and myocyte cross-sectional area were significantly reduced in the atorvastatin compared to the control group. Atorvastatin modulated expression levels of proteins related to collagen metabolism, including MMP1, TIMP1, COL I, PCPE, and SPARC, in remote infarct regions. Atorvastatin had anti-inflammatory effects, as indicated by lower expression levels of TLR4, IL-1, and NF-kB p50. Conclusion Treatment with atorvastatin for 4 weeks was able to attenuate ventricular dysfunction, fibrosis, and left ventricular hypertrophy after MI in rats, perhaps in part through effects on collagen metabolism and inflammation. Atorvastatin may be useful for limiting ventricular remodeling after myocardial ischemic events. PMID:27880844

  17. Performance of two-dimensional Doppler echocardiography for the assessment of infarct size and left ventricular function in rats

    Directory of Open Access Journals (Sweden)

    Nozawa E.

    2006-01-01

    Full Text Available Although echocardiography has been used in rats, few studies have determined its efficacy for estimating myocardial infarct size. Our objective was to estimate the myocardial infarct size, and to evaluate anatomic and functional variables of the left ventricle. Myocardial infarction was produced in 43 female Wistar rats by ligature of the left coronary artery. Echocardiography was performed 5 weeks later to measure left ventricular diameter and transverse area (mean of 3 transverse planes, infarct size (percentage of the arc with infarct on 3 transverse planes, systolic function by the change in fractional area, and diastolic function by mitral inflow parameters. The histologic measurement of myocardial infarction size was similar to the echocardiographic method. Myocardial infarct size ranged from 4.8 to 66.6% when determined by histology and from 5 to 69.8% when determined by echocardiography, with good correlation (r = 0.88; P < 0.05; Pearson correlation coefficient. Left ventricular diameter and mean diastolic transverse area correlated with myocardial infarct size by histology (r = 0.57 and r = 0.78; P < 0.0005. The fractional area change ranged from 28.5 ± 5.6 (large-size myocardial infarction to 53.1 ± 1.5% (control and correlated with myocardial infarct size by echocardiography (r = -0.87; P < 0.00001 and histology (r = -0.78; P < 00001. The E/A wave ratio of mitral inflow velocity for animals with large-size myocardial infarction (5.6 ± 2.7 was significantly higher than for all others (control: 1.9 ± 0.1; small-size myocardial infarction: 1.9 ± 0.4; moderate-size myocardial infarction: 2.8 ± 2.3. There was good agreement between echocardiographic and histologic estimates of myocardial infarct size in rats.

  18. Kinetics of lead retention and distribution in suckling and adult rats

    International Nuclear Information System (INIS)

    Momcilovic, B.; Kostial, K.

    1974-01-01

    The kinetics of lead distribution was studied in suckling and adult rats 8 days after a single intraperitoneal injection of 203 Pb. Marked differences were observed in the kinetics of lead retention and distribution in suckling as compared to adult rats. The rate of 203 Pb disappearance was lower in the whole body, blood and kidneys, but higher in the liver, while the deposition processes predominated in the brain, femur and teeth of sucklings as compared to adult animals. (auth)

  19. Different Densities of Na-Ca Exchange Current in T-Tubular and Surface Membranes and Their Impact on Cellular Activity in a Model of Rat Ventricular Cardiomyocyte

    Czech Academy of Sciences Publication Activity Database

    Pásek, Michal; Šimurda, J.; Christé, G.

    2017-01-01

    Roč. 2017, č. 2017 (2017), č. článku 6343821. ISSN 2314-6133 Institutional support: RVO:61388998 Keywords : rat ventricular cell * mathematical model * Na-Ca current * t-tubules Subject RIV: BO - Biophysics OBOR OECD: Biophysics Impact factor: 2.476, year: 2016

  20. Hypertension after bilateral kidney irradiation in young and adult rats

    International Nuclear Information System (INIS)

    Jongejan, H.T.; van der Kogel, A.J.; Provoost, A.P.; Molenaar, J.C.

    1987-01-01

    The mechanism of a rise in blood pressure after kidney irradiation is unclear but most likely of renal origin. We have investigated the role of the renin-angiotensin system and dietary salt restriction in the development of systolic hypertension after bilateral kidney irradiation in young and adult rats. Three to 12 months after a single X-ray dose of 7.5 or 12.5 Gy to both kidneys of young and adult rats, the systolic blood pressure (SBP) and plasma renin concentration (PRC) were measured regularly. A single X-ray dose of 12.5 Gy caused a moderate rise in SBP and a slight reduction in PRC in both young and adult rats. A dose of 7.5 Gy did not significantly alter the SBP or PRC during the follow-up period of 1 year. In a second experiment, the kidneys of young rats received an X-ray dose of 20 Gy. Subsequently, rats were kept on a standard diet (110 mmol sodium/kg) or a sodium-poor diet (10 mmol sodium/kg). On both diets, SBP started to rise rapidly 3 months after kidney irradiation. Sodium balance studies carried out at that time revealed an increased sodium retention in the irradiated rats compared to controls on the same diet. In rats on a low sodium intake, there was neither a delay nor an alleviation in the development of hypertension. Compared to controls, the PRC tended to be lower in irradiated rats up to 4 months after irradiation. Subsequently, malignant hypertension developed in all 20 Gy rats, resulting in pressure natriuresis, stimulating the renin-angiotensin system. Our findings indicated that hypertension after bilateral kidney irradiation was not primarily the result of an activation of the renin-angiotensin system. Although there were some indications that sodium retention played a role, dietary sodium restriction did not influence the development of hypertension

  1. chronic sleep deprevation and ventricular arrhythmias: effect of symphatic nervous system

    Directory of Open Access Journals (Sweden)

    Samira Choopani

    2016-04-01

    Full Text Available Introduction: We assessed the effect of chronic sleep deprivation on incidence of ischemia/reperfusion-induced ventricular arrhythmias (ventricular tachycardia and ventricular fibrillation and the role of the sympathetic nervous system in this respect. Material and methods: Rats were randomly divided into four groups; 1 ischemia/reperfusion group (IR: 30 minutes ischemia followed by 60 minutes reperfusion was induced, 2 control group (CON: rats has been placed in large multiple platforms for 72h prior to ischemia and reperfusion, 3 Chronic sleep deprivation group( SD: 72h sleep deprivation was induced by using small  multiple platform prior to ischemia and reperfusion, 4 Sympathectomy group (SYM: chemical sympathectomy was done 24h before to chronic sleep deprivation and then underwent ischemia and reperfusion. The heart isolated and perfused by langendorff apparatus. After thoracotomy and aorta cannulation, the hearts perfused in the langendorff apparatus using krebs-Henseleit buffer. Hearts were allowed to recovery for 15 min. After recovery period, 15 minutes was considered as baseline prior to 30 minutes ischemia followed by 60 minutes reperfusion.Tow thin stainless stell electrodes fixed on the ventricular apex and right atrium for recording the lead II of electrocardiogram (ECG.Results: There were no significant differences between heart rates between groups, and ventricular tachycardia significantly increased in chronic sleep deprivation group As compared with IR group in ischemia period. Sympathectomy significantly reduced ventricular tachycardia incidence when compared with SD. There is no difference in incidence of ventricular tachycardia between control group and IR group. The incidence of ventricular fibrillation during early reperfusion was significantly augmented (P<0.05 in sleep deprivation group as compared with IR group and Sympathectomy significantly could reverse ventricular fibrillation incidence to IR group level as

  2. Avaliação ecocardiográfica evolutiva do infarto do miocárdio em ratos jovens e adultos Echocardiographic assessment of myocardial infarction evolution in young and adult rats

    Directory of Open Access Journals (Sweden)

    Francisco Cesar Pabis

    2008-11-01

    Full Text Available FUNDAMENTO: A regeneração dos cardiomiócitos após o infarto do miocárdio (IM é mais evidente em animais jovens; entretanto, não se sabe se é acompanhada de melhora funcional. OBJETIVO: Realizar a análise funcional pela ecocardiografia (eco de ratos jovens e adultos submetidos a IM. MÉTODOS: Setenta e dois animais foram incluídos no estudo: 35 ratos jovens (grupo J com 28 dias, e 37 ratos adultos (grupo A com 153 dias. Os ratos foram subdivididos em dois subgrupos: infartado (JI e AI e controle (JC e AC. Os animais foram avaliados por meio de ecocardiograma no 7º e 30º dias de pós-operatório para análise da fração de ejeção (FE e dos volumes sistólico (VSF e diastólico (VDF finais do ventrículo esquerdo. Foram incluídos no grupo de estudo somente animais com FE menor que 40%. RESULTADOS: Na comparação dos VDF e VSF entre infartados e controles, observou-se aumento significativo nos animais adultos infartados nas duas fases analisadas. Nos animais jovens, apenas o VSF, no 7º dia, foi significativamente maior. Na evolução intragrupo, observou-se aumento do VDF e do VSF nos dois subgrupos jovens, proporcional ao crescimento, e somente aumento do VDF no grupo adulto infartado. Houve melhora da FE nos ratos jovens, enquanto nos ratos adultos a FE permaneceu diminuída em relação aos controles. CONCLUSÃO: Os ratos jovens infartados apresentaram melhora da função sistólica e dos volumes ventriculares após 30 dias do infarto, enquanto nos ratos adultos houve aumento do VDF sem melhora da função sistólica.BACKGROUND: The regeneration of cardiomyocytes after a myocardial infarction (MI is more evident in young animals; however, it is not known whether it is associated with functional improvement. OBJECTIVE: To perform the functional analysis by echocardiography (echo of young adult rats submitted to MI. METHODS: Seventy-two animals were included in the study: 35 young rats (group Y that were 28 days old and 37 adult

  3. Flow-related Right Ventricular - Pulmonary Arterial Pressure Gradients during Exercise.

    Science.gov (United States)

    Wright, Stephen P; Opotowsky, Alexander R; Buchan, Tayler A; Esfandiari, Sam; Granton, John T; Goodman, Jack M; Mak, Susanna

    2018-06-06

    The assumption of equivalence between right ventricular and pulmonary arterial systolic pressure is fundamental to several assessments of right ventricular or pulmonary vascular hemodynamic function. Our aims were to 1) determine whether systolic pressure gradients develop across the right ventricular outflow tract in healthy adults during exercise, 2) examine the potential correlates of such gradients, and 3) consider the effect of such gradients on calculated indices of right ventricular function. Healthy untrained and endurance-trained adult volunteers were studied using right-heart catheterization at rest and during submaximal cycle ergometry. Right ventricular and pulmonary artery pressures were simultaneously transduced, and cardiac output was determined by thermodilution. Systolic pressures, peak and mean gradients, and indices of chamber, vascular, and valve function were analyzed offline. Summary data are reported as mean ± standard deviation or median [interquartile range]. No significant right ventricular outflow tract gradients were observed at rest (mean gradient = 4 [3-5] mmHg), and calculated effective orifice area was 3.6±1.0 cm2. Right ventricular systolic pressure increases during exercise were greater than that of pulmonary artery systolic pressure. Accordingly, mean gradients developed during light exercise (8 [7-9] mmHg) and increased during moderate exercise (12 [9-14] mmHg, p < 0.001). The magnitude of the mean gradient was linearly related to cardiac output (r2 = 0.70, p < 0.001). In healthy adults without pulmonic stenosis, systolic pressure gradients develop during exercise, and the magnitude is related to blood flow rate.

  4. [Effect of tail-suspension on the reproduction of adult male rats].

    Science.gov (United States)

    Zhou, Dang-xia; Qiu, Shu-dong; Wang, Zhi-yong; Zhang, Jie

    2006-04-01

    To study the effects on the male reproduction in adult male rats and its mechanisms through simulated weightlessness using tail-suspension, in order to do a basic works of exploring the effects on human being's reproduction in outer space. Forty Spraque-Dawley adult male rats were randomly divided into four groups, two experimental groups and two control groups. Rats in the two experimental groups were tail-suspended for 14 d and 28 d respectively, then we examined the weight and morphology of testis, the quality and amount of sperm, also tested the serum hormone by radioimmunoassay and analyzed apoptosis rate of testicular cells by TUNEL in the experimental rats and control rats. After tail-suspension, the weight of testis, the sperm count and sperm motility significantly decreased (P 0.05). These changes were not significant between two experimental groups (P > 0.05). In addition, the seminiferous tubules became atrophy with the reduction of the layers of seminiferous epithelium, and sperm amount in lumens of seminiferous tubules decreased in experimental groups. The above were more remarkable in the 28 d experimental group. Simulating weightlessness has a harmful effect on reproduction of adult male rats. These may be caused by inducing apoptosis. The blocking apoptosis of testicular cells may be useful in improving the harmful effect.

  5. Plzf as a Candidate Gene Predisposing the Spontaneously Hypertensive Rat to Hypertension, Left Ventricular Hypertrophy, and Interstitial Fibrosis

    Czech Academy of Sciences Publication Activity Database

    Liška, F.; Mancini, M.; Krupková, M.; Chylíková, B.; Křenová, D.; Šeda, O.; Šilhavý, Jan; Mlejnek, Petr; Landa, Vladimír; Zídek, Václav; d´Amati, G.; Pravenec, Michal; Křen, Vladimír

    2014-01-01

    Roč. 27, č. 1 (2014), s. 99-106 ISSN 0895-7061 R&D Projects: GA ČR(CZ) GAP301/10/0756; GA ČR(CZ) GAP301/12/0696; GA MŠk(CZ) LL1204; GA MŠk(CZ) 7E10067 Grant - others:Univerzita Karlova(CZ) PRVOUK-P25/LF1/2 Institutional support: RVO:67985823 Keywords : hypertension * left ventricular hypertrophy * myocardial interstitial fibrosis * spontaneously hypertensive rat * Plzf (promyelocytic leukemia zinc finger) gene Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.852, year: 2014

  6. Low vagally-mediated heart rate variability and increased susceptibility to ventricular arrhythmias in rats bred for high anxiety.

    Science.gov (United States)

    Carnevali, Luca; Trombini, Mimosa; Graiani, Gallia; Madeddu, Denise; Quaini, Federico; Landgraf, Rainer; Neumann, Inga D; Nalivaiko, Eugene; Sgoifo, Andrea

    2014-04-10

    In humans, there is a documented association between anxiety disorders and cardiovascular disease. Putative underlying mechanisms may include an impairment of the autonomic nervous system control of cardiac function. The primary objective of the present study was to characterize cardiac autonomic modulation and susceptibility to arrhythmias in genetic lines of rats that differ largely in their anxiety level. To reach this goal, electrocardiographic recordings were performed in high-anxiety behavior (HAB, n=10) and low-anxiety behavior (LAB, n=10) rats at rest, during stressful stimuli and under autonomic pharmacological manipulations, and analyzed by means of time- and frequency-domain indexes of heart rate variability. During resting conditions, HAB rats displayed a reduced heart rate variability, mostly in terms of lower parasympathetic (vagal) modulation compared to LAB rats. In HAB rats, this relatively low cardiac vagal control was associated with smaller heart rate responsiveness to acute stressors compared to LAB counterparts. In addition, beta-adrenergic pharmacological stimulation induced a larger incidence of ventricular tachyarrhythmias in HABs compared to LABs. At sacrifice, a moderate increase in heart-body weight ratio was observed in HAB rats. We conclude that high levels of anxiety-related behavior in rats are associated with signs of i) impaired autonomic modulation of heart rate (low vagally-mediated heart rate variability), ii) poor adaptive heart rate responsiveness to stressful stimuli, iii) increased arrhythmia susceptibility, and iv) cardiac hypertrophy. These results highlight the utility of the HAB/LAB model for investigating the mechanistic basis of the comorbidity between anxiety disorders and cardiovascular disease. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Effect of exercise training on Ca²⁺ release units of left ventricular myocytes of spontaneously hypertensive rats.

    Science.gov (United States)

    Carneiro-Júnior, M A; Quintão-Júnior, J F; Drummond, L R; Lavorato, V N; Drummond, F R; Amadeu, M A; Oliveira, E M; Felix, L B; Cruz, J S; Mill, J G; Natali, A J; Prímola-Gomes, T N

    2014-11-01

    In cardiomyocytes, calcium (Ca²⁺) release units comprise clusters of intracellular Ca²⁺ release channels located on the sarcoplasmic reticulum, and hypertension is well established as a cause of defects in calcium release unit function. Our objective was to determine whether endurance exercise training could attenuate the deleterious effects of hypertension on calcium release unit components and Ca²⁺ sparks in left ventricular myocytes of spontaneously hypertensive rats. Male Wistar and spontaneously hypertensive rats (4 months of age) were divided into 4 groups: normotensive (NC) and hypertensive control (HC), and normotensive (NT) and hypertensive trained (HT) animals (7 rats per group). NC and HC rats were submitted to a low-intensity treadmill running protocol (5 days/week, 1 h/day, 0% grade, and 50-60% of maximal running speed) for 8 weeks. Gene expression of the ryanodine receptor type 2 (RyR2) and FK506 binding protein (FKBP12.6) increased (270%) and decreased (88%), respectively, in HC compared to NC rats. Endurance exercise training reversed these changes by reducing RyR2 (230%) and normalizing FKBP12.6 gene expression (112%). Hypertension also increased the frequency of Ca²⁺ sparks (HC=7.61 ± 0.26 vs NC=4.79 ± 0.19 per 100 µm/s) and decreased its amplitude (HC=0.260 ± 0.08 vs NC=0.324 ± 0.10 ΔF/F0), full width at half-maximum amplitude (HC=1.05 ± 0.08 vs NC=1.26 ± 0.01 µm), total duration (HC=11.51 ± 0.12 vs NC=14.97 ± 0.24 ms), time to peak (HC=4.84 ± 0.06 vs NC=6.31 ± 0.14 ms), and time constant of decay (HC=8.68 ± 0.12 vs NC=10.21 ± 0.22 ms). These changes were partially reversed in HT rats (frequency of Ca²⁺ sparks=6.26 ± 0.19 µm/s, amplitude=0.282 ± 0.10 ΔF/F0, full width at half-maximum amplitude=1.14 ± 0.01 µm, total duration=13.34 ± 0.17 ms, time to peak=5.43 ± 0.08 ms, and time constant of decay=9.43 ± 0.15 ms). Endurance exercise training attenuated the deleterious effects of hypertension on calcium release

  8. Age-dependent changes in expression of alpha1-adrenergic receptors in rat myocardium

    International Nuclear Information System (INIS)

    Schaffer, W.; Williams, R.S.

    1986-01-01

    The expression of alpha 1 -adrenergic receptors within ventricular myocardium of rats ranging in age from 21 days of fetal life to 24 months after birth was measured from [ 125 I] 2-(β hydroxy phenyl) ethylaminomethyl tetralone binding isotherms. No difference was observed in binding affinity between any of the age groups studied. The number of alpha 1 -adrenergic receptors was found to be 60-120% higher in membranes from fetal or immature rats up to 25 days of age when compared with adult animals. The increased expression of alpha 1 -adrenergic receptors in the developing heart relative to that observed in adult heart is consistent with the hypothesis that alpha 1 -adrenergic receptor stimulation may modulate protein synthesis and growth in mammalian myocardium

  9. Effects of Mercury Chloride on the Cerebral Cortex of Adult Wistar Rats

    African Journals Online (AJOL)

    Mercury is among the heavy metals that have been reported to cause devastating health problem worldwide. The primary site of action of mercury chloride is the central nervous system. This study investigated the effect of mercury chloride on the cerebral cortex of adult wistar rats. Twenty-four (24) adult wistar rats were used ...

  10. Comparison and modification of Pu-239 kinetics in young and adult rats

    International Nuclear Information System (INIS)

    Volf, V.; Gamer, A.; Laengle, U.

    1987-01-01

    It is obvious that the biokinetics of bone-seeking radionuclides are influenced by skeletal growth and remodelling, the rate of which in general decreases with increasing age. For plutonium, Mahlum and Sikov (1974) observed that rats injected with Pu-239 as weanlings retained a lower percentage in the liver and more in the bones than the animals injected as adults. However, skeletal Pu-239 was diluted more rapidly in the young rats because of intensive new bone formation and this led to a more pronounced reduction in the accumulation of radiation dose than was the case in adult animals. The aim of the present experiments was to study: a) The age effect on Pu-239 biokinetics in adult rates as influenced by the sex of the animals. b) Early retention and distribution of Pu-239 in the bones of young and adult rats injected with an optimal osteosarcomogenic dose. c) The effectiveness of a delayed prolonged administration of Zn-DTPA in drinking water for the mobilization of injected Pu-239 in rats of various age. 3 refs.; 5 figs.; 1 table

  11. Obesity and exercise-induced ectopic ventricular arrhythmias in apparently healthy middle aged adults.

    Science.gov (United States)

    Sabbag, Avi; Sidi, Yechezkel; Kivity, Shaye; Beinart, Roy; Glikson, Michael; Segev, Shlomo; Goldenberg, Ilan; Maor, Elad

    2016-03-01

    Obesity and overweight are strongly associated with cardiovascular morbidity and mortality. However, there are limited data on the association between excess weight and the risk of ectopic ventricular activity. We investigated the association between body mass index (BMI) and the risk for ectopic ventricular activity (defined as multiple ventricular premature beats (≥3), ventricular bigeminy, nonsustained ventricular tachycardia or sustained ventricular tachycardia) during exercise stress testing among 22,516 apparently healthy men and women who attended periodic health screening examinations between the years 2000 and 2014. All subjects had completed maximal exercise stress testing annually according to the Bruce protocol. Subjects were divided at baseline into three groups: normal weight (BMI ≥ 18.5 kg/m(2) andexercise-induced ectopic ventricular activity arrhythmias was highest among obese subjects, intermediate among overweight subjects and lowest among subjects with normal weight (3.4%, 2.7% and 2.2% respectively; p exercise compared with subjects with normal weight (p = 0.005), and that each 1 kg/m(2) increase in BMI was associated with a significant 4% (p = 0.002) increased adjusted risk for exercise-induced ventricular arrhythmias. Obesity is independently associated with increased likelihood of ectopic ventricular arrhythmia during exercise. © The European Society of Cardiology 2015.

  12. Maternal protein restriction compromises myocardial contractility in the young adult rat by changing proteins involved in calcium handling.

    Science.gov (United States)

    de Belchior, Aucelia C S; Freire, David D; da Costa, Carlos P; Vassallo, Dalton V; Padilha, Alessandra S; Dos Santos, Leonardo

    2016-02-01

    Maternal protein restriction (MPR) during pregnancy is associated with increased cardiovascular risk in the offspring in adulthood. In this study we evaluated the cardiac function of young male rats born from mothers subjected to MPR during pregnancy, focusing on the myocardial mechanics and calcium-handling proteins. After weaning, rats received normal diet until 3 mo old, when the following parameters were assessed: arterial and left ventricular hemodynamics and in vitro cardiac contractility in isolated papillary muscles. The body weight was lower and arterial pressure higher in the MPR group compared with young adult offspring of female rats that received standard diet (controls); and left ventricle time derivatives increased in the MPR group. The force developed by the cardiac muscle was similar; but time to peak and relaxation time were longer, and the derivatives of force were depressed in the MPR. In addition, MPR group exhibited decreased post-pause potentiation of force, suggesting reduced reuptake function of the sarcoplasmic reticulum. Corroborating, the myocardial content of SERCA-2a and phosphorylated PLB-Ser16/total PLB ratio was decreased and sodium-calcium exchanger was increased in the MPR group. The contraction dependent on transsarcolemmal influx of calcium was higher in MPR if compared with the control group. In summary, young rats born from mothers subjected to protein restriction during pregnancy exhibit changes in the myocardial mechanics with altered expression of calcium-handling proteins, reinforcing the hypothesis that maternal malnutrition is related to increased cardiovascular risk in the offspring, not only for hypertension, but also cardiac dysfunction. Copyright © 2016 the American Physiological Society.

  13. Prevention of airway hyperresponsiveness induced by left ventricular dysfunction in rats

    Directory of Open Access Journals (Sweden)

    Petak Ferenc

    2012-12-01

    Full Text Available Abstract Background The effectiveness of strategies for treatment of the altered static lung volume and against the development of bronchial hyperreactivity (BHR following a left ventricular dysfunction (LVD induced by myocardial ischaemia was investigated in a rat model of sustained postcapillary pulmonary hypertension. Methods Airway resistance (Raw was identified from the respiratory system input impedance (Zrs in four groups of rats. End-expiratory lung volume (EELV was determined plethysmographically, and Zrs was measured under baseline conditions and following iv infusions of 2, 6 or 18 μg/kg/min methacholine. Sham surgery was performed in the rats in Group C, while the left interventricular coronary artery was ligated and Zrs and its changes following identical methacholine challenges were reassessed in the same rats 8 weeks later, during which no treatment was applied (Group I, or the animals were treated daily with a combination of an angiotensin enzyme converter inhibitor and a diuretic (enalapril and furosemide, Group IE, or a calcium channel blocker (diltiazem, Group ID. The equivalent dose of methacholine causing a 100% increase in Raw (ED50 was determined in each group. Diastolic pulmonary arterial pressure (PapD was assessed by introducing a catheter into the pulmonary artery. Results The sustained presence of a LVD increased PapD in all groups of rats, with variable but significant elevations in Groups I (p = 0.004, ID (p = 0.013 and IE (p = 0.006. A LVD for 8 weeks induced no changes in baseline Raw but elevated the EELV independently of the treatments. In Group I, BHR consistently developed following the LVD, with a significant decrease in ED50 from 10.0 ± 2.5 to 6.9 ± 2.5 μg/kg/min (p = 0.006. The BHR was completely abolished in both Groups ID and IE, with no changes in ED50 (9.5 ± 3.6 vs. 10.7 ± 4.7, p = 0.33 and 10.6 ± 2.1 vs. 9.8 ± 3.5 μg/kg/min p = 0.56, respectively

  14. Evaluation of right and left ventricular function during adult respiratory distress syndrom using radionuclide angiocardiography conventional and tomographic approaches

    International Nuclear Information System (INIS)

    Devaux, J.Y.; Dhainaut, J.F.; Roucayrol, J.C.; Brunol, J.

    1982-01-01

    Despite numerous experimental and clinical studies, the cardiovascular effects of mechanical ventilation with positive-end-expiratory pressure (PEEP) are unclear. Specially, the constant fall in cardiac output is not well undestood. The purpose of this study was to investigate the effects of PEEP on right and left ventricular systolic and diastolic performance before and after volume expansion using angioscintigraphy with red blood cells, in vitro labelled with 99m Tc, a reliable, non invasive method to assess right and left ventricular dimensions and global and segmental contractility. First results in patients with adult respiratory distress syndrom (ARDS) confirm the capabilities of such a method for evaluation of regional wall motion in both ventricles

  15. Desmodium gangeticum root extract attenuates isoproterenol-induced cardiac hypertrophic growth in rats.

    OpenAIRE

    Divya Hitler; Parthasarathy Arumugam; Mathivanan Narayanasamy; Elangovan Vellaichamy

    2014-01-01

    Context: Desmodium gangeticum (L) DC (Fabaceae; DG), a medicinal plant that grows in tropical habitats, is widely used to treat various ailments including digestive and inflammatory disorders. Aims: To investigate the possible cardioprotective activity of a DG root extract against isoproterenol (ISO)-induced left ventricular cardiac hypertrophy (LVH) in adult Wistar rats. Methods: Daily intraperitoneal administration of ISO (10 mg/kg body weight, single injection) for 7 days induced LVH...

  16. Activation of calcium-sensing receptor increases TRPC3 expression in rat cardiomyocytes

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Shan-Li [Department of Clinical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086 (China); Sun, Ming-Rui [Department of Pharmacology, Qiqihaer Medical College, Qiqihaer 160001 (China); Li, Ting-Ting; Yin, Xin [Department of Clinical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086 (China); Xu, Chang-Qing [Department of Pathophysiology, Harbin Medical University, Harbin 150086 (China); Sun, Yi-Hua, E-mail: syh200415@126.com [Department of Clinical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086 (China)

    2011-03-11

    Research highlights: {yields} Calcium-sensing receptor (CaR) activation stimulates TRP channels. {yields} CaR promoted transient receptor potential C3 (TRPC3) expression. {yields} Adult rat ventricular myocytes display capacitative calcium entry (CCE), which was operated by TRPCs. {yields} TRPC channels activation induced by CaR activator sustained the increased [Ca{sup 2+}]{sub i} to evoke cardiomyocytes apoptosis. -- Abstract: Transient receptor potential (TRP) channels are expressed in cardiomyocytes, which gate a type of influx of extracellular calcium, the capacitative calcium entry. TRP channels play a role in mediating Ca{sup 2+} overload in the heart. Calcium-sensing receptors (CaR) are also expressed in rat cardiac tissue and promote the apoptosis of cardiomyocytes by Ca{sup 2+} overload. However, data about the link between CaR and TRP channels in rat heart are few. In this study, reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting were used to examine the expression of the TRP canonical proteins TRPC1 and TRPC3 in adult and neonatal rat cardiomyocytes. Laser scan confocal microscopy was used to detect intracellular [Ca{sup 2+}]{sub i} levels in isolated adult rat ventricular myocytes. The results showed that, in adult rat cardiomyocytes, the depletion of Ca{sup 2+} stores in the endoplasmic/sarcoplasmic reticulum (ER/SR) by thapsigargin induced a transient increase in [Ca{sup 2+}]{sub i} in the absence of [Ca{sup 2+}]{sub o} and the subsequent restoration of [Ca{sup 2+}]{sub o} sustained the increased [Ca{sup 2+}]{sub i} for a few minutes, whereas, the persisting elevation of [Ca{sup 2+}]{sub i} was reduced in the presence of the TRPC inhibitor SKF96365. The stimulation of CaR by its activator gadolinium chloride (GdCl{sub 3}) or spermine also resulted in the same effect and the duration of [Ca{sup 2+}]{sub i} increase was also shortened in the absence of [Ca{sup 2+}]{sub o}. In adult and neonatal rat cardiomyocytes, GdCl{sub 3

  17. Methylphenidate increases glucose uptake in the brain of young and adult rats.

    Science.gov (United States)

    Réus, Gislaine Z; Scaini, Giselli; Titus, Stephanie E; Furlanetto, Camila B; Wessler, Leticia B; Ferreira, Gabriela K; Gonçalves, Cinara L; Jeremias, Gabriela C; Quevedo, João; Streck, Emilio L

    2015-10-01

    Methylphenidate (MPH) is the drug of choice for pharmacological treatment of attention deficit hyperactivity disorder. Studies have pointed to the role of glucose and lactate as well as in the action mechanisms of drugs used to treat these neuropsychiatric diseases. Thus, this study aims to evaluate the effects of MPH administration on lactate release and glucose uptake in the brains of young and adult rats. MPH (1.0, 2.0 and 10.0mg/kg) or saline was injected in young and adult Wistar male rats either acutely (once) or chronically (once daily for 28 days). Then, the levels of lactate release and glucose uptake were assessed in the prefrontal cortex, hippocampus, striatum, cerebellum and cerebral cortex. Chronic MPH treatment increased glucose uptake at the dose of 10.0mg/kg in the prefrontal cortex and striatum, and at the dose of 2.0mg/kg in the cerebral cortex of young rats. In adult rats, an increase in glucose uptake was observed after acute administration of MPH at the dose of 10.0mg/kg in the prefrontal cortex. After chronic treatment, there was an increase in glucose uptake with MPH doses of 2.0 and 10.0mg/kg in the prefrontal cortex, and at an MPH dose of 2.0mg/kg in the striatum of adult rats. The lactate release did not change with either acute or chronic treatments in young or adult rats. These findings indicate that MPH increases glucose consumption in the brain, and that these changes are dependent on age and posology. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  18. Different Astrocytic Activation between Adult Gekko japonicus and Rats during Wound Healing In Vitro.

    Directory of Open Access Journals (Sweden)

    Yun Gu

    Full Text Available Glial scar formation is a major obstacle to regeneration after spinal cord injury. Moreover, it has been shown that the astrocytic response to injury differs between species. Gekko japonicas is a type of reptile and it shows differential glial activation compared to that of rats. The purpose of the present study was to compare the proliferation and migration of astrocytes in the spinal cords of geckos and rats after injury in vitro. Spinal cord homogenate stimulation and scratch wound models were used to induce astrocytic activation in adult and embryonic rats, as well as in adult geckos. Our results indicated that astrocytes from the adult rat were likely activated by mechanical stimulation, even though they showed lower proliferation abilities than the astrocytes from the gecko under normal conditions. Furthermore, a transcriptome analysis revealed that the differentially expressed genes in astrocytes from adult rats and those from geckos were enriched in pathways involved in proliferation and the response to stimuli. This implies that intrinsic discrepancies in gene expression patterns might contribute to the differential activation of astrocytes between species.

  19. Dietary modulation of parathion-induced neurotoxicity in adult and juvenile rats.

    Science.gov (United States)

    Liu, Jing; Karanth, Subramanya; Pope, Carey

    2005-06-01

    Previous studies indicated that dietary glucose (15% in drinking water) could markedly exacerbate the toxicity of parathion in adult rats. The present study evaluated the effect of consumption of the commonly used sweetener, high fructose corn syrup (HFCS), on parathion toxicity in adult and juvenile rats. Animals were given free access to either water or 15% HFCS in drinking water for a total of 10 days and challenged with parathion (6 or 18 mg/kg, s.c., for juveniles or adults, respectively) on the 4th day. Signs of cholinergic toxicity, body weight and chow/fluid intake were recorded daily. Acetylcholinesterase (AChE) activity and immunoreactivity (AChE-IR) in frontal cortex and diaphragm were measured at 2, 4, and 7 days after parathion. As HFCS was associated with significant reduction in chow intake, adult rats were also pair-fed to evaluate the effect of similar reduced chow intake alone on parathion toxicity. The results indicated that the cholinergic toxicity of parathion was significantly increased by HFCS feeding in both age groups. The excess sugar consumption, however, did not significantly affect parathion-induced AChE inhibition in either tissue or either age group. Enzyme immunoreactivity in frontal cortex was generally not affected in either age group while diaphragm AChE-IR was significantly reduced by parathion and HFCS alone in adult animals at 2 and 4 days timepoints, and more so by the combination of sugar feeding and parathion exposure in both age groups. Food restriction alone did not exacerbate parathion toxicity. While the mechanism(s) remains unclear, we conclude that voluntary consumption of the common sweetener HFCS can markedly amplify parathion acute toxicity in both juvenile and adult rats.

  20. Dorsally exophytic glioblastoma arising from the medulla oblongata in an adult presenting as 4th ventricular mass

    Science.gov (United States)

    Das, Kuntal Kanti; Bettaswamy, Guru Prasad; Mehrotra, Anant; Jaiswal, Sushila; Jaiswal, Awadhesh Kumar; Behari, Sanjay

    2017-01-01

    Brainstem gliomas are relatively rare in adults (medulla oblongata in a 55-year-old lady who presented with a 4th ventricular mass, and present a brief review of the literature. Till now, six cases of glioblastoma arising from the medulla oblongata have been reported. So, ours is the seventh such report. To the best of our knowledge, it also happens to be the sixth reported case of dorsally exophytic brainstem glioblastoma till date. PMID:28484537

  1. Low tidal volume ventilation ameliorates left ventricular dysfunction in mechanically ventilated rats following LPS-induced lung injury.

    Science.gov (United States)

    Cherpanath, Thomas G V; Smeding, Lonneke; Hirsch, Alexander; Lagrand, Wim K; Schultz, Marcus J; Groeneveld, A B Johan

    2015-10-07

    High tidal volume ventilation has shown to cause ventilator-induced lung injury (VILI), possibly contributing to concomitant extrapulmonary organ dysfunction. The present study examined whether left ventricular (LV) function is dependent on tidal volume size and whether this effect is augmented during lipopolysaccharide(LPS)-induced lung injury. Twenty male Wistar rats were sedated, paralyzed and then randomized in four groups receiving mechanical ventilation with tidal volumes of 6 ml/kg or 19 ml/kg with or without intrapulmonary administration of LPS. A conductance catheter was placed in the left ventricle to generate pressure-volume loops, which were also obtained within a few seconds of vena cava occlusion to obtain relatively load-independent LV systolic and diastolic function parameters. The end-systolic elastance / effective arterial elastance (Ees/Ea) ratio was used as the primary parameter of LV systolic function with the end-diastolic elastance (Eed) as primary LV diastolic function. Ees/Ea decreased over time in rats receiving LPS (p = 0.045) and high tidal volume ventilation (p = 0.007), with a lower Ees/Ea in the rats with high tidal volume ventilation plus LPS compared to the other groups (p tidal volume ventilation without LPS (p = 0.223). A significant interaction (p tidal ventilation and LPS for Ees/Ea and Eed, and all rats receiving high tidal volume ventilation plus LPS died before the end of the experiment. Low tidal volume ventilation ameliorated LV systolic and diastolic dysfunction while preventing death following LPS-induced lung injury in mechanically ventilated rats. Our data advocates the use of low tidal volumes, not only to avoid VILI, but to avert ventilator-induced myocardial dysfunction as well.

  2. Long-term organ culture of adult rat colon

    DEFF Research Database (Denmark)

    Shamsuddin, A.K.M.; Barrett, L.A.; Autrup, Herman

    1978-01-01

    . The effect of in vivo carcinogen pretreatment was also studied. The explant culture from control untreated animals showed good epithelial differentiation with crypts until 6 weeks. In contrast, the explants from animals pretreated with 4 weekly doses of azoxymethane consistently showed epithelial......Colon explants from adult rats were maintained in culture for over 3 months in our laboratories with good epithelial preservation and cellular differentiation. The light and transmission electron microscopic features of rat colon mucosa during the culture period are described. In all the explants...

  3. Immature rats show ovulatory defects similar to those in adult rats lacking prostaglandin and progesterone actions

    Directory of Open Access Journals (Sweden)

    Sanchez-Criado Jose E

    2004-09-01

    Full Text Available Abstract Gonadotropin-primed immature rats (GPIR constitute a widely used model for the study of ovulation. Although the equivalence between the ovulatory process in immature and adult rats is generally assumed, the morphological and functional characteristics of ovulation in immature rats have been scarcely considered. We describe herein the morphological aspects of the ovulatory process in GPIR and their response to classical ovulation inhibitors, such as the inhibitor of prostaglandin (PG synthesis indomethacin (INDO and a progesterone (P receptor (PR antagonist (RU486. Immature Wistar rats were primed with equine chorionic gonadotropin (eCG at 21, 23 or 25 days of age, injected with human chorionic gonadotropin (hCG 48 h later, and sacrificed 16 h after hCG treatment, to assess follicle rupture and ovulation. Surprisingly, GPIR showed age-related ovulatory defects close similar to those in adult rats lacking P and PG actions. Rats primed with eCG at 21 or 23 days of age showed abnormally ruptured corpora lutea in which the cumulus-oocyte complex (COC was trapped or had been released to the ovarian interstitum, invading the ovarian stroma and blood and lymphatic vessels. Supplementation of immature rats with exogenous P and/or PG of the E series did not significantly inhibit abnormal follicle rupture. Otherwise, ovulatory defects were practically absent in rats primed with eCG at 25 days of age. GPIR treated with INDO showed the same ovulatory alterations than vehicle-treated ones, although affecting to a higher proportion of follicles. Blocking P actions with RU486 increased the number of COC trapped inside corpora lutea and decreased ovulation. The presence of ovulatory defects in GPIR, suggests that the capacity of the immature ovary to undergo the coordinate changes leading to effective ovulation is not fully established in Wistar rats primed with eCG before 25 days of age.

  4. Desmodium gangeticum root extract attenuates isoproterenol-induced cardiac hypertrophic growth in rats.

    Directory of Open Access Journals (Sweden)

    Divya Hitler

    2014-10-01

    Full Text Available Context: Desmodium gangeticum (L DC (Fabaceae; DG, a medicinal plant that grows in tropical habitats, is widely used to treat various ailments including digestive and inflammatory disorders. Aims: To investigate the possible cardioprotective activity of a DG root extract against isoproterenol (ISO-induced left ventricular cardiac hypertrophy (LVH in adult Wistar rats. Methods: Daily intraperitoneal administration of ISO (10 mg/kg body weight, single injection for 7 days induced LVH in rats. The LVH rats were post-treated orally with DG (100 mg/kg body weight for a period of 30 days. Thereafter, changes in heart weight (HW and body weight (BW, HW/BW ratio, percent of hypertrophy, collagen accumulation, activities of matrix metalloproteinase (MMP -2 and -9, superoxide dismutase (SOD and catalase (CAT enzymes, and the level of an oxidative stress marker, lipid peroxide (LPO, were determined. Results: HW/BW ratio, an indicator of hypertrophic growth, was significantly reduced in DG root post-treated LVH rats as compared with that for the non-treated LVH rats. The altered levels of ventricular LPO, collagen, MMPs-2 and -9, and antioxidant enzymes in the ISO-treated animals reverted back to near normal upon DG treatment. Further, the anti-hypertrophic activity of DG was comparable to that of the standard drug losartan (10 mg/kg. Conclusions: The results of the present study suggest that the aqueous root extract of DG exhibited anti-hypertrophic activity in-vivo by inhibiting ISO-induced ROS generation and MMP activities.

  5. Dedifferentiation, Proliferation, and Redifferentiation of Adult Mammalian Cardiomyocytes After Ischemic Injury.

    Science.gov (United States)

    Wang, Wei Eric; Li, Liangpeng; Xia, Xuewei; Fu, Wenbin; Liao, Qiao; Lan, Cong; Yang, Dezhong; Chen, Hongmei; Yue, Rongchuan; Zeng, Cindy; Zhou, Lin; Zhou, Bin; Duan, Dayue Darrel; Chen, Xiongwen; Houser, Steven R; Zeng, Chunyu

    2017-08-29

    Adult mammalian hearts have a limited ability to generate new cardiomyocytes. Proliferation of existing adult cardiomyocytes (ACMs) is a potential source of new cardiomyocytes. Understanding the fundamental biology of ACM proliferation could be of great clinical significance for treating myocardial infarction (MI). We aim to understand the process and regulation of ACM proliferation and its role in new cardiomyocyte formation of post-MI mouse hearts. β-Actin-green fluorescent protein transgenic mice and fate-mapping Myh6-MerCreMer-tdTomato/lacZ mice were used to trace the fate of ACMs. In a coculture system with neonatal rat ventricular myocytes, ACM proliferation was documented with clear evidence of cytokinesis observed with time-lapse imaging. Cardiomyocyte proliferation in the adult mouse post-MI heart was detected by cell cycle markers and 5-ethynyl-2-deoxyuridine incorporation analysis. Echocardiography was used to measure cardiac function, and histology was performed to determine infarction size. In vitro, mononucleated and bi/multinucleated ACMs were able to proliferate at a similar rate (7.0%) in the coculture. Dedifferentiation proceeded ACM proliferation, which was followed by redifferentiation. Redifferentiation was essential to endow the daughter cells with cardiomyocyte contractile function. Intercellular propagation of Ca 2+ from contracting neonatal rat ventricular myocytes into ACM daughter cells was required to activate the Ca 2+ -dependent calcineurin-nuclear factor of activated T-cell signaling pathway to induce ACM redifferentiation. The properties of neonatal rat ventricular myocyte Ca 2+ transients influenced the rate of ACM redifferentiation. Hypoxia impaired the function of gap junctions by dephosphorylating its component protein connexin 43, the major mediator of intercellular Ca 2+ propagation between cardiomyocytes, thereby impairing ACM redifferentiation. In vivo, ACM proliferation was found primarily in the MI border zone. An ischemia

  6. Intrauterine ethanol exposure results in hypothalamic oxidative stress and neuroendocrine alterations in adult rat offspring.

    Science.gov (United States)

    Dembele, Korami; Yao, Xing-Hai; Chen, Li; Nyomba, B L Grégoire

    2006-09-01

    Prenatal ethanol (EtOH) exposure is associated with low birth weight, followed by increased appetite, catch-up growth, insulin resistance, and impaired glucose tolerance in the rat offspring. Because EtOH can induce oxidative stress, which is a putative mechanism of insulin resistance, and because of the central role of the hypothalamus in the regulation of energy homeostasis and insulin action, we investigated whether prenatal EtOH exposure causes oxidative damage to the hypothalamus, which may alter its function. Female rats were given EtOH by gavage throughout pregnancy. At birth, their offspring were smaller than those of non-EtOH rats. Markers of oxidative stress and expression of neuropeptide Y and proopiomelanocortin (POMC) were determined in hypothalami of postnatal day 7 (PD7) and 3-mo-old (adult) rat offspring. In both PD7 and adult rats, prenatal EtOH exposure was associated with decreased levels of glutathione and increased expression of MnSOD. The concentrations of lipid peroxides and protein carbonyls were normal in PD7 EtOH-exposed offspring, but were increased in adult EtOH-exposed offspring. Both PD7 and adult EtOH-exposed offspring had normal neuropeptide Y and POMC mRNA levels, but the adult offspring had reduced POMC protein concentration. Thus only adult offspring preexposed to EtOH had increased hypothalamic tissue damage and decreased levels of POMC, which could impair melanocortin signaling. We conclude that prenatal EtOH exposure causes hypothalamic oxidative stress, which persists into adult life and alters melanocortin action during adulthood. These neuroendocrine alterations may explain weight gain and insulin resistance in rats exposed to EtOH early in life.

  7. A case report of arrhythmogenic right ventricular dysplasia

    Directory of Open Access Journals (Sweden)

    Henry Anselmo Mayala

    2013-01-01

    Full Text Available Background Arrhythmogenic right ventricular dysplasia is an autosomal dominant disorder affecting parts of myocardium known as desmosomes, areas on the surface of heart muscle cells which link the cells together. The hallmark feature is fibro-fatty replacement of the right ventricle myocardium characterized by hypokinetic areas with associated arrhythmias originating in the right ventricle. CasePresentation Inthisreporta42yearoldmanwasadmittedatWuhanunion Hospital with the presenting complaints of visual hallucination and difficulty in breathing on exertion, with a family history of sudden death. Clinical and imaging findings are suggestive of Arrhythmogenic right ventricular dysplasia. Conclusion Despitebeingamongtherarecardiacdisease,Arrhythmogenicright ventricular dysplasia is an important cause of ventricular arrhythmias in children and young adults, it is also responsible for sudden cardiac death in the young population, making it necessary for this case report.

  8. Some behavioral aspects of adult rats irradiated prenatally

    International Nuclear Information System (INIS)

    Vekovishcheva, O.Yu.; Blagova, O.E.; Borovitskaya, A.E.; Evtushenko, V.I.; Khanson, K.P.

    1992-01-01

    This is a study of the effects of prenatal irradiation on the behavior of rats. The experiments were performed on 42 eighteen month old rats of both sexes. Eight of the males and thirteen females had been irradiated prenatally. The results of this experiment indicated that in general, the activation of behavior, the appearance of aggression and the increase in chaos along with the presence of behavior poses were typical of the suppressed condition of the prenatal irradiated animal. Also, among prenatally irradiated animals, there was a greater degree of anxiety, a slow rate of adjustment to unfamiliar situations and unfriendly relationships between animals of the same sex. These results were compared with the results of behavioral experiments on irradiated adult rats

  9. The effect of prenatal methamphetamine exposure on recognition memory in adult rats.

    Science.gov (United States)

    Fialová, Markéta; Šírová, Jana; Bubeníková-Valešová, Věra; Šlamberová, Romana

    2015-01-01

    The use of methamphetamine (MA) among pregnant women is an increasing world-wide health problem. Prenatal MA exposure may cause changes in foetus but the exact effects have remained unclear. The aim of this study is to present the effect of prenatal MA exposure on recognition memory in adult rats. Adult female Wistar rats were injected daily with D-methamphetamine HCl (MA; 5 mg/kg, s.c.) during the entire gestation period. Control females were treated with saline in the same regime. Adult male offspring was administrated acutely by MA (1 mg/kg i.p.) or saline 30 minutes before beginning of an experiment. For testing recognition memory two tasks were chosen: Novel Object Recognition Test (NORT) and Object Location Test (OLT). Our results demonstrate that prenatally MA-exposed animals were worse in NORT independently on an acute administration of MA in adulthood. Prenatally MA-exposed rats did not deteriorate in OLT, but after acute administration of MA in adulthood, there was significant worsening compared to appropriate control. Prenatally saline-exposed offspring did not deteriorate in any test even after acute administration of MA. Our data suggest that prenatal MA exposure in rats cause impairment in recognition memory in adult offspring, but not in spatial memory. In addition, acute administration of MA to controls did not deteriorate either recognition or spatial memory.

  10. Co-regulation of the atrial natriuretic factor and cardiac myosin light chain-2 genes during alpha-adrenergic stimulation of neonatal rat ventricular cells. Identification of cis sequences within an embryonic and a constitutive contractile protein gene which mediate inducible expression.

    Science.gov (United States)

    Knowlton, K U; Baracchini, E; Ross, R S; Harris, A N; Henderson, S A; Evans, S M; Glembotski, C C; Chien, K R

    1991-04-25

    To study the mechanisms which mediate the transcriptional activation of cardiac genes during alpha adrenergic stimulation, the present study examined the regulated expression of three cardiac genes, a ventricular embryonic gene (atrial natriuretic factor, ANF), a constitutively expressed contractile protein gene (cardiac MLC-2), and a cardiac sodium channel gene. alpha 1-Adrenergic stimulation activates the expression and release of ANF from neonatal ventricular cells. As assessed by RNase protection analyses, treatment with alpha-adrenergic agonists increases the steady-state levels of ANF mRNA by greater than 15-fold. However, a rat cardiac sodium channel gene mRNA is not induced, indicating that alpha-adrenergic stimulation does not lead to an increase in the expression of all cardiac genes. Studies employing a series of rat ANF luciferase and rat MLC-2 luciferase fusion genes identify 315- and 92-base pair cis regulatory sequences within an embryonic gene (ANF) and a constitutively expressed contractile protein gene (MLC-2), respectively, which mediate alpha-adrenergic-inducible gene expression. Transfection of various ANF luciferase reporters into neonatal rat ventricular cells demonstrated that upstream sequences which mediate tissue-specific expression (-3003 to -638) can be segregated from those responsible for inducibility. The lack of inducibility of a cardiac Na+ channel gene, and the segregation of ANF gene sequences which mediate cardiac specific from those which mediate inducible expression, provides further insight into the relationship between muscle-specific and inducible expression during cardiac myocyte hypertrophy. Based on these results, a testable model is proposed for the induction of embryonic cardiac genes and constitutively expressed contractile protein genes and the noninducibility of a subset of cardiac genes during alpha-adrenergic stimulation of neonatal rat ventricular cells.

  11. Left Ventricular Function Improves after Pulmonary Valve Replacement in Patients with Previous Right Ventricular Outflow Tract Reconstruction and Biventricular Dysfunction

    Science.gov (United States)

    Kane, Colin; Kogon, Brian; Pernetz, Maria; McConnell, Michael; Kirshbom, Paul; Rodby, Katherine; Book, Wendy M.

    2011-01-01

    Congenital heart defects that have a component of right ventricular outflow tract obstruction, such as tetralogy of Fallot, are frequently palliated in childhood by disruption of the pulmonary valve. Although this can provide an initial improvement in quality of life, these patients are often left with severe pulmonary valve insufficiency. Over time, this insufficiency can lead to enlargement of the right ventricle and to the deterioration of right ventricular systolic and diastolic function. Pulmonary valve replacement in these patients decreases right ventricular volume overload and improves right ventricular performance. To date, few studies have examined the effects of pulmonary valve replacement on left ventricular function in patients with biventricular dysfunction. We sought to perform such an evaluation. Records of adult patients who had undergone pulmonary valve replacement from January 2003 through November 2006 were analyzed retrospectively. We reviewed preoperative and postoperative echocardiograms and calculated left ventricular function in 38 patients. In the entire cohort, the mean left ventricular ejection fraction increased by a mean of 0.07 after pulmonary valve replacement, which was a statistically significant change (P < 0.01). In patients with preoperative ejection fractions of less than 0.50, mean ejection fractions increased by 0.10. We conclude that pulmonary valve replacement in patients with biventricular dysfunction arising from severe pulmonary insufficiency and right ventricular enlargement can improve left ventricular function. Prospective studies are needed to verify this finding. PMID:21720459

  12. EFFECTS OF EARLY POSTNATAL ANOXIA ON ADULT LEARNING AND EMOTION IN RATS

    NARCIS (Netherlands)

    BUWALDA, B; NYAKAS, C; VOSSELMAN, HJ; LUITEN, PGM; Vosselman, Henk Jan

    Cognitive functioning, behavioural attention and anxiety were studied in adult male Wistar rats after early postnatal anoxia. Spatial memory performance in the holeboard learning task was impaired in anoxic rats when compared with control animals. Attention assessed by the behavioural immobility

  13. Turnover time of Leydig cells and other interstitial cells in testes of adult rats

    NARCIS (Netherlands)

    Teerds, K. J.; de rooij, D. G.; Rommerts, F. F.; van der Tweel, I.; Wensing, C. J.

    1989-01-01

    The aim of this study was to investigate the turnover of Leydig cells and other interstitial cells in the adult rat testis. Normal adult rats received injections of [3H]thymidine at 9:00 and 21:00 for 2, 5, or 8 days. The percentage of labeled Leydig cells, which was initially low (0.8% +/- 0.2%),

  14. [Effect of 2,3-butanedione monoxime on calcium paradox-induced heart injury in rats].

    Science.gov (United States)

    Kong, Ling-Heng; Gu, Xiao-Ming; Su, Xing-Li; Sun, Na; Wei, Ming; Zhu, Juan-Xia; Chang, Pan; Zhou, Jing-Jun

    2016-05-01

    To investigate the Effect of 2,3-butanedione monoxime (BDM) on calcium paradox-induced heart injury and its underlying mechanisms. Thirty-two adult male SD rats were randomized into 4 groups, namely the control group, BDM treatment control group, calcium paradox group, and BDM treatment group. Isolated Sprague Dawley male rat hearts underwent Langendorff perfusion and the left ventricular pressure (LVP) and left ventricular end-diastolic pressure (LVEDP) were monitored. Left ventricular developed pressure (LVDP) was calculated to evaluate the myocardial performance. Lactate dehydrogenase (LDH) content in the coronary flow was determined. Triphenyltetrazolium chloride staining was used to measure the infarct size, and myocardial cell apoptosis was tested with TUNEL method. Western blotting was used to determine the expression of cleaved caspase-3 and cytochrome c. Compared with the control group, BDM at 20 mmol/L had no effect on cardiac performance, cell death, apoptotic index or the content of LDH, cleaved caspase-3 and cytochrome c at the end of perfusion under control conditions (P>0.05). Calcium paradox treatment significantly decreased the cardiac function and the level of LVDP and induced a larger infarct size (Pparadox, and markedly down-regulated the levels of LVEDP and LDH (Pparadox, suggesting the value of BDM as an potential drug for myocardial ischemia reperfusion injur.

  15. Acute effects of ethanol on action potential and intracellular Ca2+ transient in cardiac ventricular cells: a simulation study

    Czech Academy of Sciences Publication Activity Database

    Pásek, Michal; Bébarová, M.; Christé, G.; Šimurdová, M.; Šimurda, J.

    2016-01-01

    Roč. 54, č. 5 (2016), s. 753-762 ISSN 0140-0118 Institutional support: RVO:61388998 Keywords : ethanol * cardiomyocyte * action potential * rat ventricular cell model * human ventricular cell model Subject RIV: BO - Biophysics Impact factor: 1.916, year: 2016

  16. Ventricular Effective Refraction Period and Ventricular Repolarization Analysis in Experimental Tachycardiomyopathy in Swine.

    Science.gov (United States)

    Noszczyk-Nowak, Agnieszka; Pasławska, Urszula; Gajek, Jacek; Janiszewski, Adrian; Pasławski, Robert; Zyśko, Dorota; Nicpoń, Józef

    2016-01-01

    Swine are recognized animal models of human cardiovascular diseases. However, little is known on the CHF-associated changes in the electrophysiological ventricular parameters of humans and animals. The aim of this study was to analyze changes in the durations of ventricular effective refraction period (VERP), QT and QTc intervals of pigs with chronic tachycardia-induced tachycardiomyopathy (TIC). The study was comprised of 28 adult pigs (8 females and 20 males) of the Polish Large White breed. A one-chamber pacemaker was implanted in each of the 28 pigs. Electrocardiographic, echocardiographic and electrophysiological studies were carried out prior to the pacemaker implantation and at subsequent 4-week intervals. All electrocardiographic, echocardiographic and short electrophysiological study measurements in all swine were done under general anesthesia (propofol) after premedication with midazolam, medetomidine, and ketamine. No significant changes in the duration of QT interval and corrected QT interval (QTc) were observed during consecutive weeks of the experiment. The duration of the QTc interval of female pigs was shown to be significantly longer than that of the males throughout the whole study period. Beginning from the 12th week of rapid ventricular pacing, a significant increase in duration of VERP was observed in both male and female pigs. Males and females did not differ significantly in terms of VERP duration determined throughout the whole study period. Ventricular pacing, stimulation with 2 and 3 premature impulses at progressively shorter coupling intervals and an imposed rhythm of 130 bpm or 150 bpm induced transient ventricular tachycardia in one female pig and four male pigs. One episode of permanent ventricular tachycardia was observed. The number of induced arrhythmias increased proportionally to the severity of heart failure and duration of the experiment. However, relatively aggressive protocols of stimulation were required in order to induce

  17. The effect of hypertension on adult hippocampal neurogenesis in young adult spontaneously hypertensive rats and Dahl rats

    Czech Academy of Sciences Publication Activity Database

    Pištíková, Adéla; Brožka, Hana; Bencze, Michal; Radostová, Dominika; Valeš, Karel; Stuchlík, Aleš

    2017-01-01

    Roč. 66, č. 5 (2017), s. 881-887 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GBP304/12/G069 Grant - others:Rada Programu interní podpory projektů mezinárodní spolupráce AV ČR(CZ) M200111204 Institutional support: RVO:67985823 Keywords : adult neurogenesis * Captopril * hypertension * Dahl rats * SHR * young animals Subject RIV: FH - Neurology OBOR OECD: Neurosciences (including psychophysiology Impact factor: 1.461, year: 2016

  18. Effect of Consuming Iodized Salt on Fertility Indices in Male Adult Rats

    Directory of Open Access Journals (Sweden)

    M. Mehrabani Natanzi

    2017-06-01

    Full Text Available Introduction: Today about 27.4 percent of female 15-44 years and 1 percent of female in fertility age are affected by infertility. Iodine is a rare element that is essential for the synthesis of thyroid hormones. Concentration of the thyroid hormones in blood under the influence of iodine intake and changes in thyroid hormones levels interact with reproductive system. Today, all the people of Iran consuming iodized salt regardless of iodine status in their body. In this study according to high prevalence of the infertility among young couples, iodized salt intake on fertility in male rats were investigated. Materials and Methods: In this study 20 male and 20 female adult Wistar rats were used. Twenty male adult Wistar rats were randomly divided into 2 groups. Including the control group and treatment group that received iodine and female adult Wistar were fed with a regular diet. Five male rats from each group were killed at the end of the fourth weeks in order to evaluate the possible effect of iodized salt on sperm analysis and weight of testis. After a month, male and female rats were placed in pairs in separate cages and their offspring were investigated in terms of number, gender and health. Results: The result of this study showed that the number of healthy offspring of treated male rats was significantly lower than the control group. Conclusion: Due to the negative effect of excessive iodine intake on fertility rate, it is recommended to couples to perform functional tests of their thyroid glands before intake of iodized salts.

  19. A terrified-sound stress induced proteomic changes in adult male rat hippocampus.

    Science.gov (United States)

    Yang, Juan; Hu, Lili; Wu, Qiuhua; Liu, Liying; Zhao, Lingyu; Zhao, Xiaoge; Song, Tusheng; Huang, Chen

    2014-04-10

    In this study, we investigated the biochemical mechanisms in the adult rat hippocampus underlying the relationship between a terrified-sound induced psychological stress and spatial learning. Adult male rats were exposed to a terrified-sound stress, and the Morris water maze (MWM) has been used to evaluate changes in spatial learning and memory. The protein expression profile of the hippocampus was examined using two-dimensional gel electrophoresis (2DE), matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and bioinformatics analysis. The data from the MWM tests suggested that a terrified-sound stress improved spatial learning. The proteomic analysis revealed that the expression of 52 proteins was down-regulated, while that of 35 proteins were up-regulated, in the hippocampus of the stressed rats. We identified and validated six of the most significant differentially expressed proteins that demonstrated the greatest stress-induced changes. Our study provides the first evidence that a terrified-sound stress improves spatial learning in rats, and that the enhanced spatial learning coincides with changes in protein expression in rat hippocampus. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Extinction of conditioned cues attenuates incubation of cocaine craving in adolescent and adult rats.

    Science.gov (United States)

    Madsen, Heather B; Zbukvic, Isabel C; Luikinga, Sophia J; Lawrence, Andrew J; Kim, Jee Hyun

    2017-09-01

    Relapse to drug use is often precipitated by exposure to drug associated cues that evoke craving. Cue-induced drug craving has been observed in both animals and humans to increase over the first few weeks of abstinence and remain high over extended periods, a phenomenon known as 'incubation of craving'. As adolescence represents a period of vulnerability to developing drug addiction, potentially due to persistent reactivity to drug associated cues, we first compared incubation of cocaine craving in adolescent and adult rats. Adolescent (P35) and adult (P70) rats were trained to lever press to obtain intravenous cocaine, with each drug delivery accompanied by a light cue that served as the conditioned stimulus (CS). Following acquisition of stable responding, rats were tested for cue-induced cocaine-seeking after either 1 or 30days of abstinence. Additional groups of rats were also tested after 30days of abstinence, however these rats were subjected to a cue extinction session 1week into the abstinence period. Rats were injected with aripiprazole, a dopamine 2 receptor (D2R)-like partial agonist, or vehicle, 30min prior to cue extinction. We found that adolescent and adult rats acquired and maintained a similar level of cocaine self-administration, and rats of both ages exhibited a higher level of cue-induced cocaine-seeking if they were tested after 30days of abstinence compared to 1day. Incubation of cocaine craving was significantly reduced to 1day levels in both adults and adolescents that received cue extinction training. Administration of aripiprazole prior to cue extinction did not further reduce cue-induced drug-seeking. These results indicate that cue extinction training during abstinence may effectively reduce cue-induced relapse at a time when cue-induced drug craving is usually high. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Eating high fat chow enhances the locomotor-stimulating effects of cocaine in adolescent and adult female rats.

    Science.gov (United States)

    Baladi, Michelle G; Koek, Wouter; Aumann, Megan; Velasco, Fortino; France, Charles P

    2012-08-01

    Dopamine systems vary through development in a manner that can impact drugs acting on those systems. Dietary factors can also impact the effects of drugs acting on dopamine systems. This study examined whether eating high fat chow alters locomotor effects of cocaine (1-56 mg/kg) in adolescent and adult female rats. Cocaine was studied in rats (n = 6/group) with free access to standard (5.7% fat) or high fat (34.3%) chow or restricted access to high fat chow (body weight matched to rats eating standard chow). After 1 week of eating high fat chow (free or restricted access), sensitivity to cocaine was significantly increased in adolescent and adult rats, compared with rats eating standard chow. Sensitivity to cocaine was also increased in adolescent rats with restricted, but not free, access to high fat chow for 4 weeks. When adolescent and adult rats that previously ate high fat chow ate standard chow, sensitivity to cocaine returned to normal. In adolescent and adult female rats eating high fat chow, but not those eating standard chow, sensitivity to cocaine increased progressively over once weekly tests with cocaine (i.e., sensitization) in a manner that was not statistically different between adolescents and adults. These results show that eating high fat chow alters sensitivity of female rats to acutely administered cocaine and also facilitates the development of sensitization to cocaine. That the type of food consumed can increase drug effects might have relevance to vulnerability to abuse cocaine in the female population.

  2. L-arginine fails to prevent ventricular remodeling and heart failure in the spontaneously hypertensive rat.

    Science.gov (United States)

    Brooks, Wesley W; Conrad, Chester H; Robinson, Kathleen G; Colucci, Wilson S; Bing, Oscar H L

    2009-02-01

    The effects of long-term oral administration of L-arginine, a substrate for nitric oxide (NO) production, on left ventricular (LV) remodeling, myocardial function and the prevention of heart failure (HF) was compared to the angiotensin-converting enzyme (ACE) inhibitor captopril in a rat model of hypertensive HF (aged spontaneously hypertensive rat (SHR)). SHRs and age-matched normotensive Wistar-Kyoto (WKY) rats were assigned to either no treatment, treatment with L-arginine (7.5 g/l in drinking water) or captopril (1 g/l in drinking water) beginning at 14 months of age, a time when SHRs exhibit stable compensated hypertrophy with no hemodynamic impairment; animals were studied at 23 months of age or at the time of HF. In untreated SHR, relative to WKY, there was significant LV hypertrophy, myocardial fibrosis, and isolated LV muscle performance and response to isoproterenol (ISO) were depressed; and, 7 of 10 SHRs developed HF. Captopril administration to six SHRs attenuated hypertrophy and prevented impaired inotropic responsiveness to ISO, contractile dysfunction, fibrosis, increased passive stiffness, and HF. In contrast, L-arginine administration to SHR increased LV hypertrophy and myocardial fibrosis while cardiac performance was depressed; and 7 of 9 SHRs developed HF. In WKY, L-arginine treatment but not captopril resulted in increased LV weight and the contractile response to ISO was blunted. Neither L-arginine nor captopril treatment of WKY changed fibrosis and HF did not occur. These data demonstrate that in contrast to captopril, long-term treatment with L-arginine exacerbates age-related cardiac hypertrophy, fibrosis, and did not prevent contractile dysfunction or the development of HF in aging SHR.

  3. Analysis of testosterone effects on sonic hedgehog signaling in juvenile, adolescent and adult sprague dawley rat penis.

    Science.gov (United States)

    Bond, Christopher W; Angeloni, Nicholas L; Podlasek, Carol A

    2010-03-01

    Smooth muscle apoptosis is a major contributing factor to erectile dysfunction (ED) development in prostatectomy and diabetic patients and animal models. A critical regulator of penile smooth muscle and apoptosis is Sonic hedgehog (SHH). The SHH protein is decreased in ED models and SHH treatment of cavernous nerve (CN) injured rats prevents smooth muscle apoptosis. A close association between androgen deficiency and ED has been suggested in the literature, but few studies have examined the molecular effects on penile smooth muscle and on known signaling mechanisms that regulate morphology. Aim. Examine testosterone and SHH interaction in eugonadal adult, adolescent and juvenile rats by performing castration studies and treatment with supraphysiological testosterone. The eugonadal adult Sprague Dawley rats were either treated with testosterone for 7 or 14 days (N = 14) or were castrated for 4 or 7 days (N = 12). The juvenile rats were treated with testosterone for 8 days (N = 7). The adolescent rats were castrated and sacrificed at P88 (N = 8). The control rats had empty vehicle (N = 22) or sham surgery (N = 20). The active form of SHH protein and mRNA were quantified by semi-quantitative immunohistochemical analysis and real-time reverse transcriptase polymerase chain reaction (RT-PCR). Testosterone treatment did not alter SHH signaling in juvenile rats. Shh mRNA increased 3.2-fold and SHH protein increased 1.2-fold in rats castrated during puberty. In adult rats, castration decreased Shh mRNA 3.2-fold but did not alter SHH protein. Testosterone supplement in adult rats increased Shh mRNA 2.3-fold and decreased SHH protein 1.3-fold. SHH signaling is independent of testosterone in normal juvenile rats and is sensitive to testosterone during adolescence, while testosterone supplement in the adult adversely impacts SHH signaling in a very similar manner to that observed with CN injury.

  4. Effects of prenatal caffeine exposure on glucose homeostasis of adult offspring rats

    Science.gov (United States)

    Kou, Hao; Wang, Gui-hua; Pei, Lin-guo; Zhang, Li; Shi, Chai; Guo, Yu; Wu, Dong-fang; Wang, Hui

    2017-12-01

    Epidemiological evidences show that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR). The IUGR offspring also present glucose intolerance and type 2 diabetes mellitus after maturity. We have previously demonstrated that PCE induced IUGR and increased susceptibility to adult metabolic syndrome in rats. This study aimed to further investigate the effects of PCE on glucose homeostasis in adult offspring rats. Pregnant rats were administered caffeine (120 mg/kg/day, intragastrically) from gestational days 11 to 20. PCE offspring presented partial catch-up growth pattern after birth, characterizing by the increased body weight gain rates. Meanwhile, PCE had no significant influences on the basal blood glucose and insulin phenotypes of adult offspring but increased the glucose tolerance, glucose-stimulated insulin section and β cell sensitivity to glucose in female progeny. The insulin sensitivity of both male and female PCE offspring were enhanced accompanied with reduced β cell fraction and mass. Western blotting results revealed that significant augmentation in protein expression of hepatic insulin signaling elements of PCE females, including insulin receptor (INSR), insulin receptor substrate 1 (IRS-1) and the phosphorylation of serine-threonine protein kinase (Akt), was also potentiated. In conclusion, we demonstrated that PCE reduced the pancreatic β mass but increased the glucose tolerance in adult offspring rats, especially for females. The adaptive compensatory enhancement of β cell responsiveness to glucose and elevated insulin sensitivity mainly mediated by upregulated hepatic insulin signaling might coordinately contribute to the increased glucose tolerance.

  5. Histological changes in the cerebelli of adult wistar rats exposed to ...

    African Journals Online (AJOL)

    The different constituents of tobacco smoke have been linked to different diseased conditions. In this work, the histological effects of cigarette smoke on the cerebellum of adult male Wistar rats were studied. Sixteen Wistar rats with mean weight of 153.24 ± 4.12 g were grouped equally into four. The Control Group A was ...

  6. Modification Of Cesium Toxicity By Prussian Blue In Adult Male Albino Rats

    International Nuclear Information System (INIS)

    MANGOOD, S.A.; HAGGAG, A.M.

    2009-01-01

    The purposes of this study were to asses the toxicological effects of stable cesium chloride, and investigate the possible therapeutic role of Prussian blue (PB) in adult male albino rats.Thirty two adult male albino rats were used in this study and classified to 4 groups (8 rats/group) as follows:1- Group one (G1): rats were considered as controls and kept on the commercial diet without any treatments.2-Group two (G2): treated with daily oral cesium chloride (50 mg/300 g body weight).3-Group three (G3): treated with daily oral Prussian blue (250 mg/rats).4-Group four (G4): treated with cesium chloride at a daily oral dose of 50 mg/300 g body weight + Prussian blue at a daily oral dose of 250 mg/rats.All animals were administered the CsCl and/or PB via intubation tube and the duration of this study was 35 consecutive days. Hemoglobin (Hb), hematocrit (Ht%), red blood cells (RBC), white blood cells (WBC), folic acid, vitamin B12, total protein, albumin, globulin, A/G ratio, ALT, AST, total bilirubin, alkaline phosphatase, blood glucose, urea, creatinine, creatine phosphokinase (CPK), lactate dehydrogenase (LDH), sodium, potassium, calcium and inorganic phosphorous and body weight were determined in all groups.The data obtained revealed that the intake of stable cesium chloride in adult male rats caused significant decreases in the Hb, hematocrit, folic acid, vitamin B12 and potassium contents, with significant increases in WBC count, urea and creatinine levels and no effect on the other parameters. On the other hand, PB as a therapeutic agent caused significant amelioration in the changes produced by CsCl with variable degrees leading to the conclusion that the therapeutic agents might provide a protection against the toxicological effects of CsCl.

  7. Comparison of airway measurements during influenza-induced tachypnea in infant and adult cotton rats

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    Prince Gregory A

    2009-06-01

    Full Text Available Abstract Background Increased respiratory rate (tachypnea is frequently observed as a clinical sign of influenza pneumonia in pediatric patients admitted to the hospital. We previously demonstrated that influenza infection of adult cotton rats (Sigmodon hispidus also results in tachypnea and wanted to establish whether this clinical sign was observed in infected infant cotton rats. We hypothesized that age-dependent differences in lung mechanics result in differences in ventilatory characteristics following influenza infection. Methods Lung tidal volume, dynamic elastance, resistance, and pleural pressure were measured in a resistance and compliance system on mechanically-ventilated anesthestized young (14–28 day old and adult (6–12 week old cotton rats. Animals at the same age were infected with influenza virus, and breathing rates and other respiratory measurements were recorded using a whole body flow plethysmograph. Results Adult cotton rats had significantly greater tidal volume (TV, and lower resistance and elastance than young animals. To evaluate the impact of this increased lung capacity and stiffening on respiratory disease, young and adult animals were infected intra-nasally with influenza A/Wuhan/359/95. Both age groups had increased respiratory rate and enhanced pause (Penh during infection, suggesting lower airway obstruction. However, in spite of significant tachypnea, the infant (unlike the adult cotton rats maintained the same tidal volume, resulting in an increased minute volume. In addition, the parameters that contribute to Penh were different: while relaxation time between breaths and time of expiration was decreased in both age groups, a disproportionate increase in peak inspiratory and expiratory flow contributed to the increase in Penh in infant animals. Conclusion While respiratory rate is increased in both adult and infant influenza-infected cotton rats, the volume of air exchanged per minute (minute volume is

  8. Effects of simultaneous exposure to stress and nicotine on nicotine-induced locomotor activation in adolescent and adult rats

    Energy Technology Data Exchange (ETDEWEB)

    Zago, A. [Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP (Brazil); Leão, R.M.; Carneiro-de-Oliveira, P.E. [Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP (Brazil); Programa Interinstitucional de Pós-Graduação em Ciências Fisiológicas, Universidade Federal de São Carlos/Universidade Estadual de São Paulo, Araraquara, SP (Brazil); Marin, M.T.; Cruz, F.C. [Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP (Brazil); Planeta, C.S. [Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP (Brazil); Programa Interinstitucional de Pós-Graduação em Ciências Fisiológicas, Universidade Federal de São Carlos/Universidade Estadual de São Paulo, Araraquara, SP (Brazil)

    2011-11-18

    Preclinical studies have shown that repeated stress experiences can result in an increase in the locomotor response to the subsequent administration of drugs of abuse, a phenomenon that has been termed behavioral cross-sensitization. Behavioral sensitization reflects neuroadaptive processes associated with drug addiction and drug-induced psychosis. Although crosssensitization between stress- and drug-induced locomotor activity has been clearly demonstrated in adult rats, few studies have evaluated this phenomenon in adolescent rats. In the present study, we determined if the simultaneous exposure to stress and nicotine was capable of inducing behavioral sensitization to nicotine in adolescent and adult rats. To this end, adolescent (postnatal day (P) 28-37) and adult (P60-67) rats received nicotine (0.4 mg/kg, sc) or saline (0.9% NaCl, sc) and were immediately subjected to restraint stress for 2 h once a day for 7 days. The control group for stress was undisturbed following nicotine or saline injections. Three days after the last exposure to stress and nicotine, rats were challenged with a single dose of nicotine (0.4 mg/kg, sc) or saline and nicotine-induced locomotion was then recorded for 30 min. In adolescent rats, nicotine caused behavioral sensitization only in animals that were simultaneously exposed to stress, while in adult rats nicotine promoted sensitization independently of stress exposure. These findings demonstrate that adolescent rats are more vulnerable to the effects of stress on behavioral sensitization to nicotine than adult rats.

  9. Effects of simultaneous exposure to stress and nicotine on nicotine-induced locomotor activation in adolescent and adult rats

    International Nuclear Information System (INIS)

    Zago, A.; Leão, R.M.; Carneiro-de-Oliveira, P.E.; Marin, M.T.; Cruz, F.C.; Planeta, C.S.

    2011-01-01

    Preclinical studies have shown that repeated stress experiences can result in an increase in the locomotor response to the subsequent administration of drugs of abuse, a phenomenon that has been termed behavioral cross-sensitization. Behavioral sensitization reflects neuroadaptive processes associated with drug addiction and drug-induced psychosis. Although crosssensitization between stress- and drug-induced locomotor activity has been clearly demonstrated in adult rats, few studies have evaluated this phenomenon in adolescent rats. In the present study, we determined if the simultaneous exposure to stress and nicotine was capable of inducing behavioral sensitization to nicotine in adolescent and adult rats. To this end, adolescent (postnatal day (P) 28-37) and adult (P60-67) rats received nicotine (0.4 mg/kg, sc) or saline (0.9% NaCl, sc) and were immediately subjected to restraint stress for 2 h once a day for 7 days. The control group for stress was undisturbed following nicotine or saline injections. Three days after the last exposure to stress and nicotine, rats were challenged with a single dose of nicotine (0.4 mg/kg, sc) or saline and nicotine-induced locomotion was then recorded for 30 min. In adolescent rats, nicotine caused behavioral sensitization only in animals that were simultaneously exposed to stress, while in adult rats nicotine promoted sensitization independently of stress exposure. These findings demonstrate that adolescent rats are more vulnerable to the effects of stress on behavioral sensitization to nicotine than adult rats

  10. Effects of simultaneous exposure to stress and nicotine on nicotine-induced locomotor activation in adolescent and adult rats

    Directory of Open Access Journals (Sweden)

    A. Zago

    2012-01-01

    Full Text Available Preclinical studies have shown that repeated stress experiences can result in an increase in the locomotor response to the subsequent administration of drugs of abuse, a phenomenon that has been termed behavioral cross-sensitization. Behavioral sensitization reflects neuroadaptive processes associated with drug addiction and drug-induced psychosis. Although cross-sensitization between stress- and drug-induced locomotor activity has been clearly demonstrated in adult rats, few studies have evaluated this phenomenon in adolescent rats. In the present study, we determined if the simultaneous exposure to stress and nicotine was capable of inducing behavioral sensitization to nicotine in adolescent and adult rats. To this end, adolescent (postnatal day (P 28-37 and adult (P60-67 rats received nicotine (0.4 mg/kg, sc or saline (0.9% NaCl, sc and were immediately subjected to restraint stress for 2 h once a day for 7 days. The control group for stress was undisturbed following nicotine or saline injections. Three days after the last exposure to stress and nicotine, rats were challenged with a single dose of nicotine (0.4 mg/kg, sc or saline and nicotine-induced locomotion was then recorded for 30 min. In adolescent rats, nicotine caused behavioral sensitization only in animals that were simultaneously exposed to stress, while in adult rats nicotine promoted sensitization independently of stress exposure. These findings demonstrate that adolescent rats are more vulnerable to the effects of stress on behavioral sensitization to nicotine than adult rats.

  11. A case report of arrhythmogenic right ventricular dysplasia

    Directory of Open Access Journals (Sweden)

    Henry Anselmo Mayala

    2013-07-01

    Full Text Available Background Arrhythmogenic right ventricular dysplasia is an autosomal dominant disorder affecting parts of myocardium known as desmosomes, areas on the surface of heart muscle cells which link the cells together. The hallmark feature is fibro-fatty replacement of the right ventricle myocardium characterized by hypokinetic areas with associated arrhythmias originating in the right ventricle. Case Presentation In this report a 42 year old man was admitted at Wuhan union Hospital with the presenting complaints of visual hallucination and difficulty in breathing on exertion, with a family history of sudden death. Clinical and imaging findings are suggestive of Arrhythmogenic right ventricular dysplasia. Conclusion Despite being among the rare cardiac disease, Arrhythmogenic right ventricular dysplasia is an important cause of ventricular arrhythmias in children and young adults, it is also responsible for sudden cardiac death in the young population, making it necessary for this case report.

  12. Toluene effects on the motor activity of adolescent, young-adult, middle-age and senescent male Brown Norway rats.

    Science.gov (United States)

    MacPhail, R C; Farmer, J D; Jarema, K A

    2012-01-01

    Life stage is an important risk factor for toxicity. Children and aging adults, for example, are more susceptible to certain chemicals than are young adults. In comparison to children, relatively little is known about susceptibility in older adults. Additionally, few studies have compared toxicant susceptibility across a broad range of life stages. Results are presented for behavioral evaluations of male Brown Norway rats obtained as adolescents (1 month), or young (4 months), middle-age (12 months) and senescent (24 months) adults. Motor activity was evaluated in photocell devices during 30-min sessions. Age-related baseline characteristics and sensitivity to toluene (0, 300, 650, or 1000mg/kg, p.o.) were determined. In Experiment 1, young-adult, middle-age and senescent rats were treated with corn-oil vehicle before five weekly test sessions. Baselines of horizontal and vertical activity decreased with age, but each age-group's averages remained stable across weeks of testing. Baseline activity of older rats was more variable than that of the young adults; older rats were also more variable individually from week to week. Toluene (1000mg/kg) increased horizontal activity proportionately more in senescent rats (ca. 300% of control) than in middle-age or young-adult rats (ca.145-175% of control). Experiment 2 established toluene dose-effect functions in individual adolescent, young-adult, middle-age and senescent rats; each rat received all treatments, counterbalanced across four weekly sessions. Toluene produced dose-related increases in horizontal activity that increased proportionately with age. Experiment 3 replicated the effects of toluene (1000mg/kg) in Experiment 1, showing that toluene-induced increases in horizontal activity were greatest in the oldest rats. Collectively, the results show that aging increased susceptibility to toluene and also increased variability in toluene response. Given the rapid growth of the aged population, further research is

  13. Gastrointestinal absorption and retention of polonium in adult and newborn rats and guinea pigs

    International Nuclear Information System (INIS)

    Haines, J.W.; Naylor, G.P.L.; Pottinger, H.; Harrison, J.D.

    1993-01-01

    The gastrointestinal absorption of 210 Po was determined by comparing tissue retention after oral and systemic administration. The results indicate an increase in absorption in adult rats for 210 Po administered in liver compared with 210 Po nitrate with estimated absorption of 5 and 13%, respectively. For 210 Po citrate, values of about 7% were obtained in 1-day-old neonate and adult rats while absorption in guinea pigs was estimated to be about 23% in 1-day-old neonates, 17% in 5-day-old neonates, and 9% in adults. Gut retention of ingested 210 Po in neonates was high in rats but not guinea pigs. In adult animals, but not neonates, the liver accounted for a greater proportion of 210 Po reaching the bloodstream after ingestion than after systemic injection. The significance of these results is discussed in relation to current assumptions made in the calculation of doses from 210 Po. (author)

  14. Early life stress impairs social recognition due to a blunted response of vasopressin release within the septum of adult male rats.

    Science.gov (United States)

    Lukas, Michael; Bredewold, Remco; Landgraf, Rainer; Neumann, Inga D; Veenema, Alexa H

    2011-07-01

    Early life stress poses a risk for the development of psychopathologies characterized by disturbed emotional, social, and cognitive performance. We used maternal separation (MS, 3h daily, postnatal days 1-14) to test whether early life stress impairs social recognition performance in juvenile (5-week-old) and adult (16-week-old) male Wistar rats. Social recognition was tested in the social discrimination test and defined by increased investigation by the experimental rat towards a novel rat compared with a previously encountered rat. Juvenile control and MS rats demonstrated successful social recognition at inter-exposure intervals of 30 and 60 min. However, unlike adult control rats, adult MS rats failed to discriminate between a previously encountered and a novel rat after 60 min. The social recognition impairment of adult MS rats was accompanied by a lack of a rise in arginine vasopressin (AVP) release within the lateral septum seen during social memory acquisition in adult control rats. This blunted response of septal AVP release was social stimulus-specific because forced swimming induced a rise in septal AVP release in both control and MS rats. Retrodialysis of AVP (1 μg/ml, 3.3 μl/min, 30 min) into the lateral septum during social memory acquisition restored social recognition in adult MS rats at the 60-min interval. These studies demonstrate that MS impairs social recognition performance in adult rats, which is likely caused by blunted septal AVP activation. Impaired social recognition may be linked to MS-induced changes in other social behaviors like aggression as shown previously. Copyright © 2010 Elsevier Ltd. All rights reserved.

  15. Nicorandil prevents right ventricular remodeling by inhibiting apoptosis and lowering pressure overload in rats with pulmonary arterial hypertension.

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    Xiang-Rong Zuo

    Full Text Available BACKGROUND: Most of the deaths among patients with severe pulmonary arterial hypertension (PAH are caused by progressive right ventricular (RV pathological remodeling, dysfunction, and failure. Nicorandil can inhibit the development of PAH by reducing pulmonary artery pressure and RV hypertrophy. However, whether nicorandil can inhibit apoptosis in RV cardiomyocytes and prevent RV remodeling has been unclear. METHODOLOGY/PRINCIPAL FINDINGS: RV remodeling was induced in rats by intraperitoneal injection of monocrotaline (MCT. RV systolic pressure (RVSP was measured at the end of each week after MCT injection. Blood samples were drawn for brain natriuretic peptide (BNP ELISA analysis. The hearts were excised for histopathological, ultrastructural, immunohistochemical, and Western blotting analyses. The MCT-injected rats exhibited greater mortality and less weight gain and showed significantly increased RVSP and RV hypertrophy during the second week. These worsened during the third week. MCT injection for three weeks caused pathological RV remodeling, characterized by hypertrophy, fibrosis, dysfunction, and RV mitochondrial impairment, as indicated by increased levels of apoptosis. Nicorandil improved survival, weight gain, and RV function, ameliorated RV pressure overload, and prevented maladaptive RV remodeling in PAH rats. Nicorandil also reduced the number of apoptotic cardiomyocytes, with a concomitant increase in Bcl-2/Bax ratio. 5-hydroxydecanoate (5-HD reversed these beneficial effects of nicorandil in MCT-injected rats. CONCLUSIONS/SIGNIFICANCE: Nicorandil inhibits PAH-induced RV remodeling in rats not only by reducing RV pressure overload but also by inhibiting apoptosis in cardiomyocytes through the activation of mitochondrial ATP-sensitive K(+ (mitoK(ATP channels. The use of a mitoK(ATP channel opener such as nicorandil for PAH-associated RV remodeling and dysfunction may represent a new therapeutic strategy for the amelioration of RV

  16. c-kitpos GATA-4 high rat cardiac stem cells foster adult cardiomyocyte survival through IGF-1 paracrine signalling.

    Directory of Open Access Journals (Sweden)

    Nanako Kawaguchi

    2010-12-01

    Full Text Available Resident c-kit positive (c-kitpos cardiac stem cells (CSCs could be considered the most appropriate cell type for myocardial regeneration therapies. However, much is still unknown regarding their biological properties and potential.We produced clones of high and low expressing GATA-4 CSCs from long-term bulk-cultured c-kitpos CSCs isolated from adult rat hearts. When c-kitpos GATA-4 high expressing clonal CSCs (cCSCs were co-cultured with adult rat ventricular cardiomyocytes, we observed increased survival and contractility of the cardiomyocytes, compared to cardiomyocytes cultured alone, co-cultured with fibroblasts or c-kitpos GATA-4 low expressing cCSCs. When analysed by ELISA, the concentration of IGF-1 was significantly increased in the c-kitpos GATA-4 high cCSC/cardiomyocyte co-cultures and there was a significant correlation between IGF-1 concentration and cardiomyocyte survival. We showed the activation of the IGF-1 receptor and its downstream molecular targets in cardiomyocytes co-cultured with c-kitpos GATA-4 high cCSCs but not in cardiomyocytes that were cultured alone, co-cultured with fibroblasts or c-kitpos GATA-4 low cCSCs. Addition of a blocking antibody specific to the IGF-1 receptor inhibited the survival of cardiomyocytes and prevented the activation of its signalling in cardiomyocytes in the c-kitpos GATA-4 high cCSC/cardiomyocyte co-culture system. IGF-1 supplementation or IGF-1 high conditioned medium taken from the co-culture of c-kitpos GATA-4 high cCSCs plus cardiomyocytes did extend the survival and contractility of cardiomyocytes cultured alone and cardiomyocytes co-cultured with c-kitpos GATA-4 low cCSCs.c-kitpos GATA-4 high cCSCs exert a paracrine survival effect on cardiomyocytes through induction of the IGF-1R and signalling pathway.

  17. Effect of Amphetamine on Adult Male and Female Rats Prenatally Exposed to Methamphetamine

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    Romana Šlamberová

    2014-01-01

    Full Text Available The aim of the present study was to examine the cross-sensitization induced by prenatal methamphetamine (MA exposure to adult amphetamine (AMP treatment in male and female rats. Rat mothers received a daily injection of MA (5 mg/kg or saline throughout the gestation period. Adult male and female offspring (prenatally MA- or saline-exposed were administered with AMP (5 mg/kg or saline (1 ml/kg in adulthood. Behaviour in unknown environment was examined in open field test (Laboras, active drug-seeking behaviour in conditioned place preference test (CPP, spatial memory in the Morris water maze (MWM, and levels of corticosterone (CORT were analyzed by enzyme immunoassay (EIA. Our data demonstrate that in Laboras test, AMP treatment in adulthood increased general locomotion (time and distance travelled regardless of the prenatal exposure and sex, while AMP increased exploratory activity (rearing only in prenatally MA-exposed animals. AMP induced sensitization only in male rats, but not in females when tested drug-seeking behaviour in the CPP test. In the spatial memory MWM test, AMP worsened the performance only in females, but not in males. On the other hand, males swam faster after chronic AMP treatment regardless of the prenatal drug exposure. EIA analysis of CORT levels demonstrated higher level in females in all measurement settings. In males, prenatal MA exposure and chronic adult AMP treatment decreased CORT levels. Thus, our data demonstrated that adult AMP treatment affects behaviour of adult rats, their spatial memory and stress response in sex-specific manner. The effect is also influenced by prenatal drug exposure.

  18. Pulmonary arterial hypertension reduces energy efficiency of right, but not left, rat ventricular trabeculae.

    Science.gov (United States)

    Pham, Toan; Nisbet, Linley; Taberner, Andrew; Loiselle, Denis; Han, June-Chiew

    2018-04-01

    peak external work output was lower due to reduced extent and velocity of shortening. Despite lower peak work output, suprabasal enthalpy was unaffected, thereby rendering suprabasal efficiency lower. Crossbridge efficiency, however, was unaffected. In contrast, LV trabeculae from PAH rats maintained normal mechano-energetic performance. Pulmonary arterial hypertension reduces the suprabasal energy efficiency of hypertrophied right ventricular tissues as a consequence of the increased energy cost of Ca 2+ cycling. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

  19. Normal left ventricular mechanics by two-dimensional speckle-tracking echocardiography. Reference values in healthy adults.

    Science.gov (United States)

    Kocabay, Gonenc; Muraru, Denisa; Peluso, Diletta; Cucchini, Umberto; Mihaila, Sorina; Padayattil-Jose, Seena; Gentian, Denas; Iliceto, Sabino; Vinereanu, Dragos; Badano, Luigi P

    2014-08-01

    Two-dimensional speckle-tracking echocardiography is a novel tool to assess myocardial function. The purpose of this study was to evaluate left ventricular myocardial strain and rotation parameters by two-dimensional speckle-tracking echocardiography in a large group of healthy adults across a wide age range to establish their reference values and to assess the influence of age, sex, and hemodynamic factors. Transthoracic echocardiograms were acquired in 247 healthy volunteers (139 women, 44 years [standard deviation, 16 years old] (range, 18-80 years). We measured longitudinal, circumferential, and radial peak systolic strain values, and left ventricular rotation and twist. Average values of global longitudinal, radial, and circumferential strain were -21.5% (standard deviation, 2.0%), 40.1% (standard deviation, 11.8%) and -22.2% (standard deviation, 3.4%), respectively. Longitudinal strain was significantly more negative in women, whereas radial and circumferential strain and rotational parameters were similar in both sexes. Accordingly, lower limits of normality for the strain components were -16.9% in men and -18.5% in women for longitudinal strain, and -15.4% for circumferential and 24.6% for radial strain, irrespective of sex. Longitudinal strain values were more negative at the base than at apical segments. Mean rotational values were -6.9° (standard deviation, 3.5°) for the base, 13.0° (standard deviation, 6.5°) for apical rotation, and 20.0° (standard deviation, 7.3°) for net twist. We report the comprehensive assessment of normal myocardial deformation and rotational mechanics in a large cohort of healthy volunteers. We found that women have more negative longitudinal strain, accounting for their higher left ventricular ejection fraction. Availability of reference values for these parameters may foster their implementation in the clinical routine. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

  20. Social instability stress differentially affects amygdalar neuron adaptations and memory performance in adolescent and adult rats

    Directory of Open Access Journals (Sweden)

    Sheng-Feng eTsai

    2014-02-01

    Full Text Available Adolescence is a time of developmental changes and reorganization in the brain. It has been hypothesized that stress has a greater neurological impact on adolescents than on adults. However, scientific evidence in support of this hypothesis is still limited. We treated adolescent (4-week-old and adult (8-week-old rats with social instability stress for five weeks and compared the subsequent structural and functional changes to amygdala neurons. In the stress-free control condition, the adolescent group showed higher fear-potentiated startle responses, larger dendritic arborization, more proximal dendritic spine distribution and lower levels of truncated TrkB than the adult rats. Social instability stress exerted opposite effects on fear-potentiated startle responses in these two groups, i.e., the stress period appeared to hamper the performance in adolescents but improved it in adult rats. Furthermore, whilst the chronic social stress applied to adolescent rats reduced their dendritic field and spine density in basal and lateral amygdala neurons, the opposite stress effects on neuron morphology were observed in the adult rats. Moreover, stress in adolescence suppressed the amygdala expression of synaptic proteins, i.e., full-length TrkB and SNAP-25, whereas, in the adult rats, chronic stress enhanced full-length and truncated TrkB expressions in the amygdala. In summary, chronic social instability stress hinders amygdala neuron development in the adolescent brain, while mature neurons in the amygdala are capable of adapting to the stress. The stress induced age-dependent effects on the fear-potentiated memory may occur by altering the BDNF-TrkB signaling and neuroplasticity in the amygdala.

  1. Basement membrane chondroitin sulfate proteoglycans: localization in adult rat tissues

    DEFF Research Database (Denmark)

    McCarthy, K J; Couchman, J R

    1990-01-01

    Heparan sulfate proteoglycans have been described as the major proteoglycan component of basement membranes. However, previous investigators have also provided evidence for the presence of chondroitin sulfate glycosaminoglycan in these structures. Recently we described the production...... and characterization of core protein-specific monoclonal antibodies (MAb) against a chondroitin sulfate proteoglycan (CSPG) present in Reichert's membrane, a transient extra-embryonic structure of rodents. This CSPG was also demonstrated to be present in adult rat kidney. We report here the tissue distribution...... of epitopes recognized by these MAb. The ubiquitous presence of these epitopes in the basement membranes of nearly all adult rat tissues demonstrates that at least one CSPG is a constituent of most basement membranes, and by virtue of its unique distribution is distinct from other chondroitin and dermatan...

  2. Arrhythmogenic right ventricular cardiomyopathy: contribution of different electrocardiographic techniques.

    Science.gov (United States)

    Moreira, Davide; Delgado, Anne; Marmelo, Bruno; Correia, Emanuel; Gama, Pedro; Pipa, João; Nunes, Luís; Santos, Oliveira

    2014-04-01

    Arrhythmogenic right ventricular cardiomyopathy, also known as arrhythmogenic right ventricular dysplasia, is a condition in which myocardium is replaced by fibrous or fibrofatty tissue, predominantly in the right ventricle. It is clinically characterized by potentially lethal ventricular arrhythmias, and is a leading cause of sudden cardiac death. Its prevalence is not known exactly but is estimated at approximately 1:5000 in the adult population. Diagnosis can be on the basis of structural and functional alterations of the right ventricle, electrocardiographic abnormalities (including depolarization and repolarization alterations and ventricular arrhythmias) and family history. Diagnostic criteria facilitate the recognition and interpretation of non-specific clinical features of this disease. The authors present a case in which the diagnosis of arrhythmogenic right ventricular cardiomyopathy was prompted by the suspicion of right ventricular disease on transthoracic echocardiography. This was confirmed by detection of epsilon waves on analysis of the ECG, which generally go unnoticed but in this case were the key to the diagnosis. Their presence was also shown by non-conventional ECG techniques such as modified Fontaine ECG. The course of the disease culminated in the occurrence of ventricular tachycardia, which prompted placement of an implantable cardioverter-defibrillator. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  3. Behavioral changes in preweaning and adult rats exposed prenatally to low ionizing radiation

    International Nuclear Information System (INIS)

    Norton, S.

    1986-01-01

    Seven behavioral tests were used to evaluate the postnatal behavior of rats after exposure on gestational Day 15 to 0, 25, 50, 75, or 125 r, whole body irradiation of the pregnant rat. Three tests were administered in the first 2 postnatal weeks (righting reflex, negative geotaxis, and reflex suspension); three tests were administered on postnatal Day 21 (modified open field, spatial maze, and continuous corridor). As adults, the rats were retested with the same tests as at 21 days and also in the running wheel. Dose-response decreases in body weight were greater in the younger rats. Some behavioral tests were not altered by irradiation, while others showed clear dose-response relationships, starting as low as 25 r. The early changes were characterized by light body weight, delays in behavioral development and hypoactivity, followed by recovery of some parameters with maturation. Eventually hyperactivity developed in adult rats after gestational irradiation. However, it cannot be concluded that either morphological or behavioral tests are more sensitive than neonatal body weight change for detection of damage from gestational irradiation

  4. Use of gated N-13-NH3 micro-PET to examine left ventricular function in rats

    NARCIS (Netherlands)

    Szymanski, Mariusz K.; Kruizinga, Silvana; Tio, Rene A.; Willemsen, Antoon T. M.; Schaefers, Michael A.; Stegger, Lars; Dierckx, Rudi A.; Hillege, Hans L.; Slart, Riemer H. J. A.

    Introduction: Myocardial perfusion gating techniques offer the possibility of measurement of left ventricular end-systolic (ESV) and end-diastolic volume (EDV) and left ventricular ejection fraction (LVEF) in clinical and preclinical trials. The aim of this study was to evaluate left ventricular

  5. Intrauterine programming mechanism for hypercholesterolemia in prenatal caffeine-exposed female adult rat offspring.

    Science.gov (United States)

    Xu, Dan; Luo, Hanwen W; Hu, Wen; Hu, Shuwei W; Yuan, Chao; Wang, Guihua H; Zhang, Li; Yu, Hong; Magdalou, Jacques; Chen, Liaobin B; Wang, Hui

    2018-05-02

    Clinical and animal studies have indicated that hypercholesterolemia and its associated diseases have intrauterine developmental origins. Our previous studies showed that prenatal caffeine exposure (PCE) led to fetal overexposure to maternal glucocorticoids (GCs) and increased serum total cholesterol levels in adult rat offspring. This study further confirms the intrauterine programming of PCE-induced hypercholesterolemia in female adult rat offspring. Pregnant Wistar rats were intragastrically administered caffeine (30, 60, and 120 mg/kg/d) from gestational day (GD)9 to 20. Female rat offspring were euthanized at GD20 and postnatal wk 12; several adult rat offspring were additionally subjected to ice-water swimming stimulation to induce chronic stress prior to death. The effects of GCs on cholesterol metabolism and epigenetic regulation were verified using the L02 cell line. The results showed that PCE induced hypercholesterolemia in adult offspring, which manifested as significantly higher levels of serum total cholesterol and LDL cholesterol (LDL-C) as well as higher ratios of LDL-C/HDL cholesterol. We further found that the cholesterol levels were increased in fetal livers but were decreased in fetal blood, accompanied by increased maternal blood cholesterol levels and reduced placental cholesterol transport. Furthermore, analysis of PCE offspring in the uterus and in a postnatal basal/chronic stress state and the results of in vitro experiments showed that hepatic cholesterol metabolism underwent GC-dependent changes and was associated with cholesterol synthase via abnormalities in 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) histone acetylation. We concluded that, to compensate for intrauterine placentally derived decreases in fetal blood cholesterol levels, high intrauterine GC levels activated fetal hepatic CCAAT enhancer binding protein α signaling and down-regulated Sirtuin1 expression, which mediated the high levels of histone acetylation ( via H3K9

  6. Enhanced mesenchymal cell engraftment by IGF-1 improves left ventricular function in rats undergoing myocardial infarction.

    Science.gov (United States)

    Enoki, Chiharu; Otani, Hajime; Sato, Daisuke; Okada, Takayuki; Hattori, Reiji; Imamura, Hiroji

    2010-01-07

    We hypothesized that enhanced mesenchymal cell (MC) engraftment with insulin-like growth factor-1 (IGF-1) improves left ventricular (LV) function and survival. IGF-1 (10 microg/ml) increased adhesion and inhibited apoptosis under hypoxia in vitro through activation of phosphatidylinositol 3-kinase (PI3K) in bone marrow-derived MCs obtained from transgenic rats expressing green fluorescence protein. Myocardial infarction (MI) in rats was produced by ligature of the left coronary artery. One month after MI, rat hearts were injected with MCs in the presence or absence of 10 microg/ml IGF-1 with or without PI3K inhibitor, 5 microM LY294002. IGF-1 significantly increased engraftment of MCs between 6 h and 3 days after transplantation associated with the increase in stromal cell-derived factor-1alpha in the infracted LV. The transplanted MCs had disappeared 1 month after transplantation in all groups. MC transplantation with IGF-1 significantly increased neovascularization and inhibited cardiomyocyte apoptosis 3 days and 1 month after MC transplantation. This was associated with improved LV function 1 month after MC transplantation and eventually survival. LY294002 abrogated all of the beneficial effects of MC transplantation with IGF-1. IGF-1 alone had no effect on neovascularization and did not improve LV function and/or survival. These results suggest that IGF-1 improves engraftment of MCs at the time of transplantation via activation of PI3K and this improved engraftment of MCs may be attributed to an increased neovascularization and inhibition of cardiomyocyte death, leading to improvement of LV function and prolongation of survival despite the eventual loss of the transplanted MCs.

  7. Islands of spatially discordant APD alternans underlie arrhythmogenesis by promoting electrotonic dyssynchrony in models of fibrotic rat ventricular myocardium

    Science.gov (United States)

    Majumder, Rupamanjari; Engels, Marc C.; de Vries, Antoine A. F.; Panfilov, Alexander V.; Pijnappels, Daniël A.

    2016-04-01

    Fibrosis and altered gap junctional coupling are key features of ventricular remodelling and are associated with abnormal electrical impulse generation and propagation. Such abnormalities predispose to reentrant electrical activity in the heart. In the absence of tissue heterogeneity, high-frequency impulse generation can also induce dynamic electrical instabilities leading to reentrant arrhythmias. However, because of the complexity and stochastic nature of such arrhythmias, the combined effects of tissue heterogeneity and dynamical instabilities in these arrhythmias have not been explored in detail. Here, arrhythmogenesis was studied using in vitro and in silico monolayer models of neonatal rat ventricular tissue with 30% randomly distributed cardiac myofibroblasts and systematically lowered intercellular coupling achieved in vitro through graded knockdown of connexin43 expression. Arrhythmia incidence and complexity increased with decreasing intercellular coupling efficiency. This coincided with the onset of a specialized type of spatially discordant action potential duration alternans characterized by island-like areas of opposite alternans phase, which positively correlated with the degree of connexinx43 knockdown and arrhythmia complexity. At higher myofibroblast densities, more of these islands were formed and reentrant arrhythmias were more easily induced. This is the first study exploring the combinatorial effects of myocardial fibrosis and dynamic electrical instabilities on reentrant arrhythmia initiation and complexity.

  8. Influence of superior cervical ganglionectomy on hippocampal neurogenesis and learning and memory in adult rats

    Institute of Scientific and Technical Information of China (English)

    Yanping Ding; Baoping Shao; Shiyuan Yu; Shanting Zhao; Jianlin Wang

    2009-01-01

    BACKGROUND: Studies have shown that neurogenesis in the dentate gyrus plays an important role in learning and memory. However, studies have not determined whether the superior cervical ganglion or the sympathetic nerve system influences hippocampal neurogenesis or learning and memory in adult rats. OBJECTIVE: To observe differences in dentate gyrus neurogenesis, as well as learning and memory, in adult rats following superior cervical ganglionectomy. DESIGN, TIME AND SETTING: A randomized, controlled, animal study was performed at the Immunohistochemistry Laboratory of the School of Life Sciences in Lanzhou University from July 2006 to July 2007.MATERIALS: Doublecortin polyclonal antibody was provided by Santa Cruz Biotechnology, USA;avidin-biotin-peroxidase complex was purchased from Zhongshan Goldenbride Biotechnology, China;Morris water maze was bought from Taimeng Technology, China. METHODS: A total of 20 adult, male, Wistar rats were randomly divided into surgery and control groups, with 10 rats in each group. In the surgery group, the bilateral superior cervical ganglions were transected. In the control group, the superior cervical ganglions were only exposed, but no ganglionectomy was performed. MAIN OUTCOME MEASURES: To examine distribution, morphology, and number of newborn neurons in the dentate gyrus using doublecortin immunohistochemistry at 36 days following surgical procedures. To examine ability of learning and memory in adult rats using the Morris water maze at 30 days following surgical procedures. RESULTS: Doublecortin immunohistochemical results showed that a reduction in the number of doublecortin-positive neurons in the surgery group compared to the control group (P<0.05), while the distribution of doublecortin-positive neurons was identical in the two groups. The surgery group exhibited significantly worse performance in learning and spatial memory tasks compared to the control group (P<0.05). CONCLUSION: Superior cervical ganglionectomy

  9. Effects of acute and chronic administration of fenproporex on DNA damage parameters in young and adult rats.

    Science.gov (United States)

    Gonçalves, Cinara L; Rezin, Gislaine T; Ferreira, Gabriela K; Jeremias, Isabela C; Cardoso, Mariane R; Valvassori, Samira S; Munhoz, Bruna J P; Borges, Gabriela D; Bristot, Bruno N; Leffa, Daniela D; Andrade, Vanessa M; Quevedo, João; Streck, Emilio L

    2013-08-01

    Obesity is a chronic and multifactorial disease, whose prevalence is increasing in many countries. Pharmaceutical strategies for the treatment of obesity include drugs that regulate food intake, thermogenesis, fat absorption, and fat metabolism. Fenproporex is the second most commonly consumed amphetamine-based anorectic worldwide; this drug is rapidly converted in vivo into amphetamine, which is associated with neurotoxicity. In this context, the present study evaluated DNA damage parameters in the peripheral blood of young and adult rats submitted to an acute administration and chronic administration of fenproporex. In the acute administration, both young and adult rats received a single injection of fenproporex (6.25, 12.5 or 25 mg/kg i.p.) or vehicle. In the chronic administration, both young and adult rats received one daily injection of fenproporex (6.25, 12.5, or 25 mg/kg i.p.) or Tween for 14 days. 2 h after the last injection, the rats were killed by decapitation and their peripheral blood removed for evaluation of DNA damage parameters by alkaline comet assay. Our study showed that acute administration of fenproporex in young and adult rats presented higher levels of damage index and frequency in the DNA. However, chronic administration of fenproporex in young and adult rats did not alter the levels of DNA damage in both parameters of comet assay. The present findings showed that acute administration of fenproporex promoted damage in DNA, in both young and adult rats. Our results are consistent with other reports which showed that other amphetamine-derived drugs also caused DNA damage. We suggest that the activation of an efficient DNA repair mechanism may occur after chronic exposition to fenproporex. Our results are consistent with other reports that showed some amphetamine-derived drugs also caused DNA damage.

  10. Copolymer-1 enhances cognitive performance in young adult rats

    Science.gov (United States)

    Meneses, Alfredo; Cruz-Martínez, Yolanda; Anaya-Jiménez, Rosa María; Liy-Salmerón, Gustavo; Carvajal, Horacio Guillermo; Ponce-López, Maria Teresa

    2018-01-01

    Cognitive impairment is a dysfunction observed as a sequel of various neurodegenerative diseases, as well as a concomitant element in the elderly stages of life. In clinical settings, this malfunction is identified as mild cognitive impairment. Previous studies have suggested that cognitive impairment could be the result of a reduction in the expression of brain-derived neurotrophic factor (BDNF) and/or immune dysfunction. Copolymer-1 (Cop-1) is an FDA-approved synthetic peptide capable of inducing the activation of Th2/3 cells, which are able to release BDNF, as well as to migrate and accumulate in the brain. In this study, we evaluated the effect of Cop-1 immunization on improvement of cognition in adult rats. For this purpose, we performed four experiments. We evaluated the effect of Cop-1 immunization on learning/memory using the Morris water maze for spatial memory and autoshaping for associative memory in 3- or 6-month-old rats. BDNF concentrations at the hippocampus were determined by ELISA. Cop-1 immunization induced a significant improvement of spatial memory and associative memory in 6-month-old rats. Likewise, Cop-1 improved spatial memory and associative memory when animals were immunized at 3 months and evaluated at 6 months old. Additionally, Cop-1 induced a significant increase in BDNF levels at the hippocampus. To our knowledge, the present investigation reports the first instance of Cop-1 treatment enhancing cognitive function in normal young adult rats, suggesting that Cop-1 may be a practical therapeutic strategy potentially useful for age- or disease-related cognitive impairment. PMID:29494605

  11. Long-term pretreatment with desethylamiodarone (DEA) or amiodarone (AMIO) protects against coronary artery occlusion induced ventricular arrhythmias in conscious rats.

    Science.gov (United States)

    Morvay, Nikolett; Baczkó, István; Sztojkov-Ivanov, Anita; Falkay, György; Papp, Julius Gy; Varró, András; Leprán, István

    2015-09-01

    The aim of this investigation was to compare the effectiveness of long-term pretreatment with amiodarone (AMIO) and its active metabolite desethylamiodarone (DEA) on arrhythmias induced by acute myocardial infarction in rats. Acute myocardial infarction was induced in conscious, male, Sprague-Dawley rats by pulling a previously inserted loose silk loop around the left main coronary artery. Long-term oral pretreatment with AMIO (30 or 100 mg·(kg body mass)(-1)·day(-1), loading dose 100 or 300 mg·kg(-1) for 3 days) or DEA (15 or 50 mg·kg(-1)·day(-1), loading dose 100 or 300 mg·kg(-1) for 3 days), was applied for 1 month before the coronary artery occlusion. Chronic oral treatment with DEA (50 mg·kg(-1)·day(-1)) resulted in a similar myocardial DEA concentration as chronic AMIO treatment (100 mg·kg(-1)·day(-1)) in rats (7.4 ± 0.7 μg·g(-1) and 8.9 ± 2.2 μg·g(-1)). Both pretreatments in the larger doses significantly improved the survival rate during the acute phase of experimental myocardial infarction (82% and 64% by AMIO and DEA, respectively, vs. 31% in controls). Our results demonstrate that chronic oral treatment with DEA resulted in similar cardiac tissue levels to that of chronic AMIO treatment, and offered an equivalent degree of antiarrhythmic effect against acute coronary artery ligation induced ventricular arrhythmias in conscious rats.

  12. August rats are more resistant to arrhythmogenic effect of myocardial ischemia and reperfusion than Wistar rats.

    Science.gov (United States)

    Belkina, L M; Kirillina, T N; Pshennikova, M G; Arkhipenko, Yu V

    2002-06-01

    As differentiated from Wistar rats, myocardial ischemia and reperfusion produce no ventricular fibrillation in August rats. Pretreatment with nitric oxide synthase inhibitor Nw-nitro-L-arginine increased mortality rate in August rats with acute myocardial infarction from 20 to 40%. Under these conditions mortality rate in Wistar rats increased from 50 to 71%. Interstrain differences in the resistance of these animals to the arrhythmogenic effect of ischemia are probably associated with higher activity of the nitric oxide system in August rats compared to Wistar rats.

  13. Transient severe left ventricular dysfunction following percutaneous patent ductus arteriosus closure in an adult with bicuspid aortic valve: A case report.

    Science.gov (United States)

    Hwang, Hui-Jeong; Yoon, Kyung Lim; Sohn, Il Suk

    2016-03-01

    The present study reported the case of a 60-year-old female with patent ductus arteriosus (PDA) and a bicuspid aortic valve, who presented with transient severe left ventricular (LV) dysfunction following percutaneous closure of PDA, as identified by speckle tracking analysis. Transient LV dysfunction following PDA closure has previously been reported; however, severe LV dysfunction is rare. In the present case, the combination of a large PDA size, large amount of shunting, LV remodeling and bicuspid aortic valve may have induced serious deterioration of LV function following PDA closure. Furthermore, speckle-tracking echocardiography may be useful in the estimation of functional alterations in the myocardium of the LV following PDA closure. The observations detailed in the present study may improve the understanding of the pathophysiology and myocardial patterns of transient left ventricular dysfunction following PDA closure in adult humans.

  14. Aging-Dependent Changes in the Radiation Response of the Adult Rat Brain

    International Nuclear Information System (INIS)

    Schindler, Matthew K.; Forbes, M. Elizabeth; Robbins, Mike E.; Riddle, David R.

    2008-01-01

    Purpose: To assess the impact of aging on the radiation response in the adult rat brain. Methods and Materials: Male rats 8, 18, or 28 months of age received a single 10-Gy dose of whole-brain irradiation (WBI). The hippocampal dentate gyrus was analyzed 1 and 10 weeks later for sensitive neurobiologic markers associated with radiation-induced damage: changes in density of proliferating cells, immature neurons, total microglia, and activated microglia. Results: A significant decrease in basal levels of proliferating cells and immature neurons and increased microglial activation occurred with normal aging. The WBI induced a transient increase in proliferation that was greater in older animals. This proliferation response did not increase the number of immature neurons, which decreased after WBI in young rats, but not in old rats. Total microglial numbers decreased after WBI at all ages, but microglial activation increased markedly, particularly in older animals. Conclusions: Age is an important factor to consider when investigating the radiation response of the brain. In contrast to young adults, older rats show no sustained decrease in number of immature neurons after WBI, but have a greater inflammatory response. The latter may have an enhanced role in the development of radiation-induced cognitive dysfunction in older individuals

  15. Tooth movement characteristics in relation to root resorption in young and adult rats.

    NARCIS (Netherlands)

    Ren, Y.; Maltha, J.C.; Kuijpers-Jagtman, A.M.

    2007-01-01

    The aim of this study was to investigate tooth movement characteristics in relation to root resorption in young and adult rats. Two groups of 30 rats each (aged 6 wk and 9-12 months, respectively) were used. Standardized orthodontic appliances were placed to move the maxillary molars mesially.

  16. Tooth movement characteristics in relation to root resorption in young and adult rats

    NARCIS (Netherlands)

    Ren, Yijin; Maltha, Jaap C.; Kuijpers-Jagtman, Anne Marie

    2007-01-01

    The aim of this study was to investigate tooth movement characteristics in relation to root resorption in young and adult rats. Two groups of 30 rats each (aged 6 wk and 9-12 months, respectively) were used. Standardized orthodontic appliances were placed to move the maxillary molars mesially.

  17. Ghrelin modulates testicular germ cells apoptosis and proliferation in adult normal rats

    International Nuclear Information System (INIS)

    Kheradmand, Arash; Dezfoulian, Omid; Alirezaei, Masoud; Rasoulian, Bahram

    2012-01-01

    Highlights: ► Spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. ► Numerous studies have documented the direct action of ghrelin in the modulation of apoptosis in different cell types. ► Ghrelin may be considered as a modulator of spermatogenesis in normal adult rats. ► Ghrelin may be potentially implicated for abnormal spermatogenesis in some testicular germ cell tumors. -- Abstract: Under normal condition in the most mammals, spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. The present study was designed to determine the effects of ghrelin treatment on in vivo quality and quantity expression of apoptosis and proliferation specific indices in rat testicular germ cells. Twenty eight adult normal rats were subdivided into equal control and treatment groups. Treatment group received 3 nmol of ghrelin as subcutaneous injection for 30 consecutive days or vehicle to the control animals. The rats from each group (n = 7) were killed on days 10 and 30 and their testes were taken for immunocytochemical evaluation and caspase-3 assay. Immunohistochemical analysis indicated that the accumulations of Bax and PCNA peptides are generally more prominent in spermatocytes and spermatogonia of both groups. Likewise, the mean percentage of immunoreactive spermatocytes against Bax increased (P 0.05). Upstream of Bax substance parallel to down-regulation of PCNA demonstrate that ghrelin may prevent massive accumulation of germ cells during normal spermatogenesis. These observations also indicate that ghrelin may be considered as a modulator of spermatogenesis in normal adult rats and could be potentially implicated for abnormal spermatogenesis in some testicular germ cell tumors.

  18. Substance P Differentially Modulates Firing Rate of Solitary Complex (SC) Neurons from Control and Chronic Hypoxia-Adapted Adult Rats

    Science.gov (United States)

    Nichols, Nicole L.; Powell, Frank L.; Dean, Jay B.; Putnam, Robert W.

    2014-01-01

    NK1 receptors, which bind substance P, are present in the majority of brainstem regions that contain CO2/H+-sensitive neurons that play a role in central chemosensitivity. However, the effect of substance P on the chemosensitive response of neurons from these regions has not been studied. Hypoxia increases substance P release from peripheral afferents that terminate in the caudal nucleus tractus solitarius (NTS). Here we studied the effect of substance P on the chemosensitive responses of solitary complex (SC: NTS and dorsal motor nucleus) neurons from control and chronic hypoxia-adapted (CHx) adult rats. We simultaneously measured intracellular pH and electrical responses to hypercapnic acidosis in SC neurons from control and CHx adult rats using the blind whole cell patch clamp technique and fluorescence imaging microscopy. Substance P significantly increased the basal firing rate in SC neurons from control and CHx rats, although the increase was smaller in CHx rats. However, substance P did not affect the chemosensitive response of SC neurons from either group of rats. In conclusion, we found that substance P plays a role in modulating the basal firing rate of SC neurons but the magnitude of the effect is smaller for SC neurons from CHx adult rats, implying that NK1 receptors may be down regulated in CHx adult rats. Substance P does not appear to play a role in modulating the firing rate response to hypercapnic acidosis of SC neurons from either control or CHx adult rats. PMID:24516602

  19. Can prenatal low-dose irradiation affect behavior of adult rats?

    International Nuclear Information System (INIS)

    Smajda, B.; Tomasova, L.; Kokocova, N.

    2011-01-01

    The aim of our study was to determine whether exposure of very low dose gamma-rays during the critical phase of brain development affects some selected behavioral parameters in adult rats. Pregnant female Wistar rats were irradiated with 1 Gy gamma-rays from a cobalt source at 17 th day of pregnancy. The progeniture of irradiated as well as non-irradiated females have undergone behavioral tests at the age of 3 months. Irradiated animals exhibited lower locomotor and exploratory activity in the open field test. (authors)

  20. Two-Dimensional Speckle Tracking Echocardiography Detects Subclinical Left Ventricular Systolic Dysfunction among Adult Survivors of Childhood, Adolescent, and Young Adult Cancer

    Directory of Open Access Journals (Sweden)

    Anthony F. Yu

    2016-01-01

    Full Text Available Two-dimensional speckle tracking echocardiography (2DSTE provides a sensitive measure of left ventricular (LV systolic function and may aid in the diagnosis of cardiotoxicity. 2DSTE was performed in a cross-sectional study of 134 patients (mean age: 31.4±8.8 years; 55% male; mean time since diagnosis: 15.4±9.4 years previously treated with anthracyclines (mean cumulative dose: 320±124 mg/m2, with (n=52 or without (n=82 mediastinal radiotherapy. The prevalence of LV systolic dysfunction, defined as fractional shortening < 27%, LV ejection fraction (LVEF < 55%, and global longitudinal strain (GLS ≤ 16%, was 5.2%, 6.0%, and 23.1%, respectively. Abnormal GLS was observed in 24 (18% patients despite a normal LVEF. Indices of LV systolic function were similar regardless of anthracycline dose. However, GLS was worse (18.0 versus 19.0, p=0.003 and prevalence of abnormal GLS was higher (36.5% versus 14.6%, p=0.004 in patients treated with mediastinal radiotherapy. Mediastinal radiotherapy was associated with reduced GLS (p=0.040 after adjusting for sex, age, and cumulative anthracycline dose. In adult survivors of childhood, adolescent, and young adult cancer, 2DSTE frequently detects LV systolic dysfunction despite a normal LVEF and may be useful for the long-term cardiac surveillance of adult cancer survivors.

  1. Right ventricular function and N-terminal pro-brain natriuretic peptide levels in adult patients with simple dextro-transposition of the great arteries.

    Science.gov (United States)

    Martínez-Quintana, Efrén; Marrero-Negrín, Natalia; Gopar-Gopar, Silvia; Rodríguez-González, Fayna

    2017-06-01

    Dextro-transposition of the great arteries (d-TGA) patients is at high risk of developing right ventricular dysfunction and tricuspid regurgitation in adulthood. Determining the relation between echocardiographic parameters, N-terminal pro-brain natriuretic peptide (NT-pro-BNP) levels and the New York Heart Association (NYHA) functional class may help determining the best time to operate them. Patients with simple d-TGA operated in infancy with an atrial switch procedure (Mustard or Senning operation) were followed up in our Adult Congenital Heart Disease Unit. Analytical, echocardiographic, and clinical parameters were determined to evaluate the correlation between right echocardiographic ventricular function, NT-pro-BNP levels, and NYHA functional class. Twenty-four patients with d-TGA were operated in infancy of whom 17 alive patients had simple d-TGA. Nine patients had NT-pro-BNP levels lower than 200 pg/mL and eight patients were above 200 pg/mL. Patients with lower hemoglobin concentration, higher right ventricular diameter or under diuretic treatment showed significant higher NT-pro-BNP levels (above 200 pg/dL). The Spearman test showed a positive correlation between basal right ventricular diameter and tricuspid regurgitation with pro NT BNP levels (correlation coefficient of .624; P=.017 and .490; P=.046, respectively) and a negative correlation with the right ventricle fractional area change (-.508, P=.045). No correlation was seen between NT-pro-BNP levels and the rest of echocardiographic parameters or the NYHA functional class. NT-pro-BNP levels showed a positive correlation with basal right ventricular diameter and tricuspid regurgitation but not with NYHA association functional class in d-TGA patients. © 2017, Wiley Periodicals, Inc.

  2. Acute and Chronic Effects of Dietary Lactose in Adult Rats Are not Explained by Residual Intestinal Lactase Activity.

    Science.gov (United States)

    van de Heijning, Bert J M; Kegler, Diane; Schipper, Lidewij; Voogd, Eline; Oosting, Annemarie; van der Beek, Eline M

    2015-07-08

    Neonatal rats have a high intestinal lactase activity, which declines around weaning. Yet, the effects of lactose-containing products are often studied in adult animals. This report is on the residual, post-weaning lactase activity and on the short- and long-term effects of lactose exposure in adult rats. Acutely, the postprandial plasma response to increasing doses of lactose was studied, and chronically, the effects of a 30% lactose diet fed from postnatal (PN) Day 15 onwards were evaluated. Intestinal lactase activity, as assessed both in vivo and in vitro, was compared between both test methods and diet groups (lactose vs. control). A 50%-75% decreased digestive capability towards lactose was observed from weaning into adulthood. Instillation of lactose in adult rats showed disproportionally low increases in plasma glucose levels and did not elicit an insulin response. However, gavages comprising maltodextrin gave rise to significant plasma glucose and insulin responses, indicative of a bias of the adult GI tract to digest glucose polymers. Despite the residual intestinal lactase activity shown, a 30% lactose diet was poorly digested by adult rats: the lactose diet rendered the animals less heavy and virtually devoid of body fat, whereas their cecum tripled in size, suggesting an increased bacterial fermentation. The observed acute and chronic effects of lactose exposure in adult rats cannot be explained by the residual intestinal lactase activity assessed.

  3. Left ventricular remodeling and change of systolic function after closure of patent ductus arteriosus in adults: device and surgical closure.

    Science.gov (United States)

    Jeong, Young-Hoon; Yun, Tae-Jin; Song, Jong-Min; Park, Jung-Jun; Seo, Dong-Man; Koh, Jae-Kon; Lee, Se-Whan; Kim, Mi-Jeong; Kang, Duk-Hyun; Song, Jae-Kwan

    2007-09-01

    Left ventricular (LV) remodeling and predictors of LV systolic function late after closure of patent ductus arteriosus (PDA) in adults remain to be clearly demonstrated. In 45 patients with PDA, including 28 patients who received successful occlusion using the Amplatzer device (AD group) (AGA, Golden Valley, MN) and 17 patients who received surgical closure (OP group), echocardiography studies were performed before closure and 1 day (AD group) or within 7 days (OP group) after closure, and then were repeated at > or = 6 months (17 +/- 13 months). In both groups, LV ejection fraction (EF) and end-diastolic volume index were significantly decreased immediately after closure, whereas end-systolic volume index did not change. During the long-term follow-up period, end-systolic as well as end-diastolic volume indices decreased significantly in both groups and LV EF recovered compared to the immediate postclosure state. However, LV EF remained low compared to the preclosure state. Five patients (11.1%) including 3 patients in the AD group and 2 patients in the OP group showed persistent late LV systolic dysfunction (EF or = 62% had a sensitivity of 72% and a specificity of 83% for predicting late normal LV EF after closure. Left ventricular EF remains low late after PDA closure compared with preclosure state in adults. Preclosure LV EF is the best index to predict late postclosure LV EF.

  4. Competition among oxidizable substrates in brains of young and adult rats. Dissociated cells.

    OpenAIRE

    Roeder, L M; Tildon, J T; Holman, D C

    1984-01-01

    The rates of conversion of D-(-)-3-hydroxy[3-14C]butyrate, [3-14C]acetoacetate, [6-14C]glucose and [U-14C]glutamine into 14CO2 were measured in the presence and absence of alternative oxidizable substrates in intact dissociated cells from the brains of young and adult rats. When unlabelled glutamine was added to [6-14C]glucose or unlabelled glucose was added to [U-14C]glutamine, the rate of 14CO2 production was decreased in both young and adult rats. The rate of oxidation of 3-hydroxy[3-14C]b...

  5. Maternal nutrient restriction during pregnancy and lactation leads to impaired right ventricular function in young adult baboons.

    Science.gov (United States)

    Kuo, Anderson H; Li, Cun; Huber, Hillary F; Schwab, Matthias; Nathanielsz, Peter W; Clarke, Geoffrey D

    2017-07-01

    Maternal nutrient restriction induces intrauterine growth restriction (IUGR) and leads to heightened cardiovascular risks later in life. We report right ventricular (RV) filling and ejection abnormalities in IUGR young adult baboons using cardiac magnetic resonance imaging. Both functional and morphological indicators of poor RV function were seen, many of which were similar to effects of ageing, but also with a few key differences. We observed more pronounced RV changes compared to our previous report of the left ventricle, suggesting there is likely to be a component of isolated RV abnormality in addition to expected haemodynamic sequelae from left ventricular dysfunction. In particular, our findings raise the suspicion of pulmonary hypertension after IUGR. This study establishes that IUGR also leads to impairment of the right ventricle in addition to the left ventricle classically studied. Maternal nutrient restriction induces intrauterine growth restriction (IUGR), increasing later life chronic disease including cardiovascular dysfunction. Our left ventricular (LV) CMRI studies in IUGR baboons (8 M, 8 F, 5.7 years - human equivalent approximately 25 years), control offspring (8 M, 8 F, 5.6 years), and normal elderly (OLD) baboons (6 M, 6 F, mean 15.9 years) revealed long-term LV abnormalities in IUGR offspring. Although it is known that right ventricular (RV) function is dependent on LV health, the IUGR right ventricle remains poorly studied. We examined the right ventricle with cardiac magnetic resonance imaging in the same cohorts. We observed decreased ejection fraction (49 ± 2 vs. 33 ± 3%, P < 0.001), cardiac index (2.73 ± 0.27 vs. 1.89 ± 0.20 l min -1 m -2 , P < 0.05), early filling rate/body surface area (BSA) (109.2 ± 7.8 vs. 44.6 ± 7.3 ml s -1  m -2 , P < 0.001), wall thickening (61 ± 3 vs. 44 ± 5%, P < 0.05), and longitudinal shortening (26 ± 3 vs. 15 ± 2%, P < 0.01) in IUGR animals with increased

  6. Long-term effects of 239Pu injection in adult, weanling, newborn and fetal rats

    International Nuclear Information System (INIS)

    Sikov, M.R.; Mahlum, D.D.; Hess, J.O.; Carr, D.B.

    1979-01-01

    We have completed biological evaluations comparing long-term effects in rats exposed to 239 Pu citrate as adults, weanlings, newborns, or late fetuses, and statistical analyses have been initiated. In rats exposed postnatally, statistically significant alterations in terminal body weight and in weights of several organs were found at higher doses. Survivorship decreased with increasing dose in the postnatal groups, but not in rats exposed prenatally

  7. Left Ventricular Hypertrophy in Pediatric Hypertension: A Mini Review

    Directory of Open Access Journals (Sweden)

    Robert P. Woroniecki

    2017-05-01

    Full Text Available Adults with arterial hypertension (HTN have stroke, myocardial infarction, end-stage renal disease (ESRD, or die at higher rates than those without. In children, HTN leads to target organ damage, which includes kidney, brain, eye, blood vessels, and heart, which precedes “hard outcomes” observed in adults. Left ventricular hypertrophy (LVH or an anatomic and pathologic increase in left ventricular mass (LVM in response to the HTN is a pediatric surrogate marker for HTN-induced morbidity and mortality in adults. This mini review discusses current definitions, clinically relevant methods of LVM measurements and normalization methods, its epidemiology, management, and issue of reversibility in children with HTN. Pediatric definition of LVH and abnormal LVM is not uniformed. With multiple definitions, prevalence of pediatric HTN-induced LVH is difficult to ascertain. In addition while in adults cardiac magnetic resonance imaging is considered “the gold standard” for LVM and LVH determination, pediatric data are limited to “special populations”: ESRD, transplant, and obese children. We summarize available data on pediatric LVH treatment and reversibility and offer future directions in addressing LVH in children with HTN.

  8. Substance P differentially modulates firing rate of solitary complex (SC neurons from control and chronic hypoxia-adapted adult rats.

    Directory of Open Access Journals (Sweden)

    Nicole L Nichols

    Full Text Available NK1 receptors, which bind substance P, are present in the majority of brainstem regions that contain CO2/H(+-sensitive neurons that play a role in central chemosensitivity. However, the effect of substance P on the chemosensitive response of neurons from these regions has not been studied. Hypoxia increases substance P release from peripheral afferents that terminate in the caudal nucleus tractus solitarius (NTS. Here we studied the effect of substance P on the chemosensitive responses of solitary complex (SC: NTS and dorsal motor nucleus neurons from control and chronic hypoxia-adapted (CHx adult rats. We simultaneously measured intracellular pH and electrical responses to hypercapnic acidosis in SC neurons from control and CHx adult rats using the blind whole cell patch clamp technique and fluorescence imaging microscopy. Substance P significantly increased the basal firing rate in SC neurons from control and CHx rats, although the increase was smaller in CHx rats. However, substance P did not affect the chemosensitive response of SC neurons from either group of rats. In conclusion, we found that substance P plays a role in modulating the basal firing rate of SC neurons but the magnitude of the effect is smaller for SC neurons from CHx adult rats, implying that NK1 receptors may be down regulated in CHx adult rats. Substance P does not appear to play a role in modulating the firing rate response to hypercapnic acidosis of SC neurons from either control or CHx adult rats.

  9. Differential effects of magnetic field exposure from domestic power supply on loco motor and exploratory behavior of an adult rat

    International Nuclear Information System (INIS)

    Anandavadivel, A.; Caleo, M.

    2011-01-01

    In the present study, we have examined the low intense magnetic field exposed on adult rats to understand effect of several behavioral parameters. The rats are tested in the open field and spontaneous alternation task after either a single or chronic exposure to the magnetic field. We found that magnetic field exposure had no effect on locomotor behavior in the adult. However, the exploratory behavior of adult rats in the open field was significantly affected. Indeed, we found a consistent increase in behavior performance viz. exploration time and number of exploration events in rats exposed to magnetic field. Our results demonstrate behavioral changes after magnetic field exposure in adult subjects. This also suggests possible deleterious effects of magnetic field exposure in the brain. (author)

  10. Automated Assessment of Left Ventricular Function and Mass Using Heart Deformation Analysis: Initial Experience in 160 Older Adults.

    Science.gov (United States)

    Lin, Kai; Collins, Jeremy D; Lloyd-Jones, Donald M; Jolly, Marie-Pierre; Li, Debiao; Markl, Michael; Carr, James C

    2016-03-01

    To assess the performance of automated quantification of left ventricular function and mass based on heart deformation analysis (HDA) in asymptomatic older adults. This study complied with Health Insurance Portability and Accountability Act regulations. Following the approval of the institutional review board, 160 asymptomatic older participants were recruited for cardiac magnetic resonance imaging including two-dimensional cine images covering the entire left ventricle in short-axis view. Data analysis included the calculation of left ventricular ejection fraction (LVEF), left ventricular mass (LVM), and cardiac output (CO) using HDA and standard global cardiac function analysis (delineation of end-systolic and end-diastolic left ventricle epi- and endocardial borders). The agreement between methods was evaluated using intraclass correlation coefficient (ICC) and coefficient of variation (CoV). HDA had a shorter processing time than the standard method (1.5 ± 0.3 min/case vs. 5.8 ± 1.4 min/case, P HDA. There was a systemic bias toward lower LVEF (62.8% ± 8.3% vs. 69.3% ± 6.7%, P HDA compared to the standard technique. Conversely, HDA overestimated LVM (114.8 ± 30.1 g vs. 100.2 ± 29.0 g, P HDA has the potential to measure LVEF, CO, and LVM without the need for user interaction based on standard cardiac two-dimensional cine images. Copyright © 2015 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  11. The local expression of adult chicken heart myosins during development. II. Ventricular conducting tissue

    NARCIS (Netherlands)

    Sanders, E.; de Groot, I. J.; Geerts, W. J.; de Jong, F.; van Horssen, A. A.; Los, J. A.; Moorman, A. F.

    1986-01-01

    The development of the ventricular conducting tissue of the embryonic chicken heart has been studied using a previous finding that morphologically recognizable atrial conducting tissue coexpresses the atrial and the ventricular myosin isoforms. It is found that, by these criteria, at 9 days part of

  12. Cardio-protective effects of carnitine in streptozotocin-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Malone Michael A

    2006-01-01

    Full Text Available Abstract Background Streptozotocin-induced diabetes (STZ-D in rats has been associated with carnitine deficiency, bradycardia and left ventricular enlargement. Aim The purpose of this study was to determine whether oral carnitine supplementation would normalize carnitine levels and cardiac function in STZ-D rats. Methods Wistar rats (48 were made hyperglycemic by STZ at 26 weeks of age. Same age normal Wistar rats (24 were used for comparison. Echocardiograms were performed at baseline 2, 6, 10, and 18 weeks after STZ administration in all animals. HbA1c, serum carnitine and free fatty acids (FFA were measured at the same times. Since STZ-D rats become carnitine deficient, 15 STZ-D rats received supplemental oral carnitine for 16 weeks. Results The heart rates for the STZ-D rats (290 ± 19 bpm were less than control rats (324 ± 20 bpm (p Conclusion Thus, supplemental oral carnitine in STZ-D rats normalized serum carnitine, heart rate regulation and left ventricular size. These findings suggest a metabolic mechanism for the cardiac dysfunction noted in this diabetic animal model.

  13. Comparison of Quantitative Characteristics of Early Post-resuscitation EEG Between Asphyxial and Ventricular Fibrillation Cardiac Arrest in Rats.

    Science.gov (United States)

    Chen, Bihua; Chen, Gang; Dai, Chenxi; Wang, Pei; Zhang, Lei; Huang, Yuanyuan; Li, Yongqin

    2018-04-01

    Quantitative electroencephalogram (EEG) analysis has shown promising results in studying brain injury and functional recovery after cardiac arrest (CA). However, whether the quantitative characteristics of EEG, as potential indicators of neurological prognosis, are influenced by CA causes is unknown. The purpose of this study was designed to compare the quantitative characteristics of early post-resuscitation EEG between asphyxial CA (ACA) and ventricular fibrillation CA (VFCA) in rats. Thirty-two Sprague-Dawley rats of both sexes were randomized into either ACA or VFCA group. Cardiopulmonary resuscitation was initiated after 5-min untreated CA. Characteristics of early post-resuscitation EEG were compared, and the relationships between quantitative EEG features and neurological outcomes were investigated. Compared with VFCA, serum level of S100B, neurological deficit score and brain histopathologic damage score were dramatically higher in the ACA group. Quantitative measures of EEG, including onset time of EEG burst, time to normal trace, burst suppression ratio, and information quantity, were significantly lower for CA caused by asphyxia and correlated with the 96-h neurological outcome and survival. Characteristics of earlier post-resuscitation EEG differed between cardiac and respiratory causes. Quantitative measures of EEG not only predicted neurological outcome and survival, but also have the potential to stratify CA with different causes.

  14. The rate of cerebral utilization of glucose, ketone bodies, and oxygen: a comparative in vivo study of infant and adult rats.

    Science.gov (United States)

    Dahlquist, G; Persson, B

    1976-11-01

    Cerebral blood flow (CBF) was measured by means of Celabeled microspheres in infant (20-day-old) and adult (3-month-old) rats, anesthetised with Na-5-ethyl-5-(1-methylpropyl)2-thiobarbituric acid. Cerebral arteriovenous differences of acetoacetate, D-beta-hydroxybutyrate, glucose, lactate, and oxygen and brain DNA content were determined in other groups of similarly treated infant and adult animals fed or starved for 48 or 72 hr. The mean CBF values of 0.48+/-0.04 and 0.62+/-0.07 ml/(g X min), +/- SEM, in infant and adult animals, respectively, were not significantly different. CBF was unaffected by starvation. At any given arterial concentration the cerebral arteriovenous difference of acetoacetate was significantly higher in infant than adult rats. The same was true for D-beta-hydroxybutyrate at arterial concentrations above 1 mmol/liter. There was an approximately linear relationship between arterial concentration of acetoacetate and its cerebral arteriovenous difference in both infant and adult rats. A similar relationship was found for D-beta-hydroxybutyrate only in infant animals. In the fed state, the cerebral uptake of glucose and ketone bodies (micromoles per (mg DNA X min)) was not different in infant and adult rats. During starvation, cerebral uptake of ketone bodies expressed as micromoles per (mg DNA X min) was higher in infant than adult rats, indicating a higher rate of utilization of ketone bodies per cell in these animals. For glucose, no such difference was found in either fed or starved groups (Table 3). The average percentage of the total cerebral uptake of substrates (micromoles per min) accounted for by ketone bodies increased in both infant and adult rats during starvation. This percentage value was clearly higher in infant than adult rats during starvation. After 72 hr of starvation the values were 38.8% and 15.2% in infant and adult rats, respectively (Fig. 3). Calculated cerebral metabolic rate for oxygen (CMRO2), assuming complete

  15. Rapid reorganization of adult rat motor cortex somatic representation patterns after motor nerve injury.

    OpenAIRE

    Sanes, J N; Suner, S; Lando, J F; Donoghue, J P

    1988-01-01

    The potential for peripheral nerve injury to reorganize motor cortical representations was investigated in adult rats. Maps reflecting functional connections between the motor cortex and somatic musculature were generated with intracortical electrical stimulation techniques. Comparison of cortical somatotopic maps obtained in normal rats with maps generated from rats with a facial nerve lesion indicated that the forelimb and eye/eyelid representations expanded into the normal vibrissa area. R...

  16. Sexual odor discrimination and physiological profiles in adult male rats after a neonatal, short term, reversible nasal obstruction.

    Science.gov (United States)

    Thornton, S N; Padzys, G S; Trabalon, M

    2014-05-01

    The present study was designed to examine behavioral responses (interpreted as preferences) to olfactory cues (nest bedding odor and odors of estrous and anestrus females) in adult male rats after they had a short term reversible, bilateral, nasal obstruction (RbNO) as developing rat pups. These results were compared to behavior of control (untreated) and sham operated male littermates. Behavioral tests and physiological parameters were analyzed 90 days after recovery of nasal breathing. Experiments investigated the time spent in arms or the center of a maze of male rats in response to odors from the nest bedding or from adult females. There were no differences in responses between untreated, sham and RbNO adult male rats to fresh and nest bedding odors. RbNO males spent more time in the center of the maze when given a choice of estrus or anestrus female odors, or bedding odors from untreated or sham operated female rats. In contrast untreated and sham male rats preferred the odors of estrous females and of untreated or sham females. Plasma corticosterone levels in the males increased during the behavioral tests. Plasma testosterone levels were significantly lower in RbNO males compared to untreated males and did not increase during the behavioral tests compared to sham operated males. Males from all groups had similar preferences for the odor of bedding from adult RbNO females. Plasma levels of cholesterol and triglycerides were increased in RbNO adults. In conclusion, short term nasal obstruction in males while juvenile has long term consequences on hormones and behavioral preferences, thus potential partner selection when adult. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Effect of hydration status on atrial and ventricular volumes and function in healthy adult volunteers

    Energy Technology Data Exchange (ETDEWEB)

    Schantz, Daryl I. [The Hospital for Sick Children, The Labatt Family Heart Centre in the Department of Paediatrics, Toronto, ON (Canada); University of Manitoba, Variety Children' s Heart Centre, Winnipeg, MB (Canada); Dragulescu, Andreea [The Hospital for Sick Children, The Labatt Family Heart Centre in the Department of Paediatrics, Toronto, ON (Canada); Memauri, Brett [University of Manitoba, Department of Radiology, St. Boniface General Hospital, Winnipeg, MB (Canada); Grotenhuis, Heynric B. [The Hospital for Sick Children, The Labatt Family Heart Centre in the Department of Paediatrics, Toronto, ON (Canada); Wilhelmina Children' s Hospital, Utrecht (Netherlands); Seed, Mike; Grosse-Wortmann, Lars [The Hospital for Sick Children, The Labatt Family Heart Centre in the Department of Paediatrics, Toronto, ON (Canada); The Hospital for Sick Children, Department of Diagnostic Imaging, Toronto, ON (Canada)

    2016-10-15

    Assessment of cardiac chamber volumes is a fundamental part of cardiac magnetic resonance (CMR) imaging. While the effects of inter- and intraobserver variability have been studied and have a recognized effect on the comparability of serial cardiac MR imaging studies, the effect of differences in hydration status has not been evaluated. To evaluate the effects of volume administration on cardiac chamber volumes. Thirteen healthy adults underwent a baseline cardiac MR to evaluate cardiac chamber volumes after an overnight fast. They were then given two saline boluses of 10 ml/kg of body weight and the cardiac MR was repeated immediately after each bolus. From the baseline scan to the final scan there was a significant increase in all four cardiac chamber end-diastolic volumes. Right atrial volumes increased 8.0%, from 61.1 to 66.0 ml/m2 (P<0.001), and left atrial volumes increased 10.0%, from 50.0 to 55.0 ml/m2 (P<0.001). Right ventricular volumes increased 6.0%, from 91.1 to 96.5 ml/m2 (P<0.001), and left ventricular volumes increased 3.2%, from 87.0 to 89.8 ml/m2 (P<0.001). Hydration status has a significant effect on the end-diastolic volumes of all cardiac chambers assessed by cardiac MR. Thus, hydration represents a ''variable'' that should be taken into account when assessing cardiac chamber volumes, especially when performing serial imaging studies in a patient. (orig.)

  18. Effect of hydration status on atrial and ventricular volumes and function in healthy adult volunteers

    International Nuclear Information System (INIS)

    Schantz, Daryl I.; Dragulescu, Andreea; Memauri, Brett; Grotenhuis, Heynric B.; Seed, Mike; Grosse-Wortmann, Lars

    2016-01-01

    Assessment of cardiac chamber volumes is a fundamental part of cardiac magnetic resonance (CMR) imaging. While the effects of inter- and intraobserver variability have been studied and have a recognized effect on the comparability of serial cardiac MR imaging studies, the effect of differences in hydration status has not been evaluated. To evaluate the effects of volume administration on cardiac chamber volumes. Thirteen healthy adults underwent a baseline cardiac MR to evaluate cardiac chamber volumes after an overnight fast. They were then given two saline boluses of 10 ml/kg of body weight and the cardiac MR was repeated immediately after each bolus. From the baseline scan to the final scan there was a significant increase in all four cardiac chamber end-diastolic volumes. Right atrial volumes increased 8.0%, from 61.1 to 66.0 ml/m2 (P<0.001), and left atrial volumes increased 10.0%, from 50.0 to 55.0 ml/m2 (P<0.001). Right ventricular volumes increased 6.0%, from 91.1 to 96.5 ml/m2 (P<0.001), and left ventricular volumes increased 3.2%, from 87.0 to 89.8 ml/m2 (P<0.001). Hydration status has a significant effect on the end-diastolic volumes of all cardiac chambers assessed by cardiac MR. Thus, hydration represents a ''variable'' that should be taken into account when assessing cardiac chamber volumes, especially when performing serial imaging studies in a patient. (orig.)

  19. In vivo and in vitro dermal penetration of 2,4,5,2',4', 5'-hexachlorobiphenyl in young and adult rats

    International Nuclear Information System (INIS)

    Shah, P.V.; Sumler, M.R.; Fisher, H.L.; Hall, L.L.

    1989-01-01

    Penetration of 2,4,5,2',4',5'-[ 14 C]hexachlorobiphenyl (HCB) through skin of young (33 days) and adult (82 days) female Fischer 344 rats was determined in vivo and by two in vitro methods. In vivo dermal penetration at 120 hr was 45% in young and 43% in adults. At 72 hr in vivo dermal penetration was 35% in young and 26% in adults compared to 1.5% for young and 1.0% for adult as measured with a continuous flow in vitro system and 2.9% for young and 1.9% for adults as measured with a static in vitro system. Most of the dermally absorbed HCB remained in the body as only 4.9 and 2.6% of that absorbed was excreted by young and adult rats, respectively, at the end of 120 hr. Significant differences in dermal penetration and kinetics of HCB between young and adult female rats were observed. The elimination of ECB-derived material was approximately six times higher in feces than in urine. A physiological pharmacokinetic model was fitted to the organ and tissue radioactivity distribution data. Parameters in the model determined from dermal dosing of female Fischer 344 rats were in reasonable agreement with those reported in the literature for adult male Sprague-Dawley rats (iv dose). The rate constant for dermal penetration was 0.83 x 10 -4 min -1 for adults and 0.96 x 10 -4 min -1 for young. The delay or lag time parameter for dermal penetration was 4.4 hr in adults and 1.1 hr in young

  20. [Expression of connective tissue growth factor in cardiomyocyte of young rats with heart failure and benazepril intervention].

    Science.gov (United States)

    Zhang, Qin; Yi, Qi-jian; Qian, Yong-ru; Li, Rong; Deng, Bing; Wang, Qiao

    2006-10-01

    Ventricular remodeling is an important pathologic progress in almost all end stage heart failure (HF), and it is characterized by ventricular thickening and cardiac fibrosis with poor prognosis. The connective tissue growth factor (CTGF), a new growth factor with multi-function, has an important role in fibrosis of tissue and organs. It has been demonstrated that angiotensin-converting enzyme inhibitor (ACEI) can prevent the development of cardiomyocyte from remodeling and improve cardiac function. Researchers try to test the hypothesis that cardiac function improvement attributable to ACEI is associated with inhibiting expression of CTGF in patients with HF. The aim of this study was to observe changes in CTGF expression in cardiomyocyte of young rats with HF and effect of benazepril on CTGF. The animal model of HF was established by constriction of abdominal aorta. Five weeks old rats were randomly divided into 3 groups after 6 weeks of operation: (1) HF group without treatment (n = 15); (2) HF group where rats were treated with benazepril (n = 15); (3) sham-operated group (n = 15) where rats were administered benazepril through direct gastric gavage. After 4 weeks of treatment, the high frequency ultrasound was performed. The expression of CTGF was detected by immunohistochemistry and semi-quantative reverse transcription-polymerase chain reaction. Compared with the sham-operated group, left ventricular diastolic dimension (LVEDD), left ventricular systolic dimension (LVESD), interventricular septal thickness at end-diastole (IVSTd), interventricular septal thickness at end-systole (IVSTs), left ventricular posterior wall thickness at end-diastole (LVPWTd), left ventricular posterior wall thickness at end-systole (LVPWTs), left ventricular relative weight (LVRW), and right ventricular relative weight (RVRW) were all increased (P benazepril when compared with HF group without treatment. LVESD, IVSTd, IVSTs, LVPWTd, LVPWTs, LVRW and RVRW were higher (P benazepril

  1. Adolescent TBI-induced hypopituitarism causes sexual dysfunction in adult male rats.

    Science.gov (United States)

    Greco, Tiffany; Hovda, David A; Prins, Mayumi L

    2015-02-01

    Adolescents are at greatest risk for traumatic brain injury (TBI) and repeat TBI (RTBI). TBI-induced hypopituitarism has been documented in both adults and juveniles and despite the necessity of pituitary function for normal physical and brain development, it is still unrecognized and untreated in adolescents following TBI. TBI induced hormonal dysfunction during a critical developmental window has the potential to cause long-term cognitive and behavioral deficits and the topic currently remains unaddressed. The purpose of this study was to determine if four mild TBIs delivered to adolescent male rats disrupts testosterone production and adult behavioral outcomes. Plasma testosterone was quantified from 72 hrs preinjury to 3 months postinjury and pubertal onset, reproductive organ growth, erectile function and reproductive behaviors were assessed at 1 and 2 months postinjury. RTBI resulted in both acute and chronic decreases in testosterone production and delayed onset of puberty. Significant deficits were observed in reproductive organ growth, erectile function and reproductive behaviors in adult rats at both 1 and 2 months postinjury. These data suggest adolescent RTBI-induced hypopituitarism underlies abnormal behavioral changes observed during adulthood. The impact of undiagnosed hypopituitarism following RTBI in adolescence has significance not only for growth and puberty, but also for brain development and neurobehavioral function as adults. © 2014 Wiley Periodicals, Inc.

  2. Ventricular Ganglioneuroblastoma in an Adult and Successful Treatment with Radiotherapy

    Directory of Open Access Journals (Sweden)

    Mustafa Akın

    2014-06-01

    Full Text Available Background: Ganglioneuroblastomas (GNBs are rare embryonic neoplasms in the spectrum of neuroblastic tumours and 80% of cases occur in the first decade. In adults, GNBs are usually located in the retroperitoneum, mediastinum and neck but intracranial GNBs are extremely rare. Case Report: A 34-year-old male applied to the Department of Neurology outpatient clinic with a two month history of headache and numbness in his legs. Detailed examinations and cranial CT were performed and showed a mass with a 5 cm diameter running from the third to the fourth ventricle. Referral to a neurosurgeon was performed for partial removal of the tumour, as the histological and immunohistochemical studies defined the diagnosis of GNB. Three months later, when the patient experienced dizziness, an MRI was performed, which showed a 4x3 cm ventricular mass, with hypointense characterisation in T1-weighted and hyperintense characteristics in T2-weighted and flair sequences. Afterwards, fractioned radiotherapy (54 Gy/30 fx was chosen as the appropriate therapy. In the follow-up period, MRI was performed 3 months and 1 year after treatment, and revealed shrinkage of the tumour by at least 50%. Meanwhile the patient’s post-irradiation course was favourable. Conclusion: Data following the use of radiotherapy as treatment for intracranial GNB showing favourable results has been reported.

  3. Adult neurogenesis and its anatomical context in the hippocampus of three mole-rat species

    Directory of Open Access Journals (Sweden)

    Irmgard eAmrein

    2014-05-01

    Full Text Available African mole-rats (family Bathyergidae are small to medium sized, long-lived and strictly subterranean rodents that became valuable animal models as a result of their longevity and diversity in social organization. The formation and integration of new hippocampal neurons in adult mammals (adult hippocampal neurogenesis, AHN correlates negatively with age and positively with habitat complexity. Here we present quantitative data on AHN in wild-derived mole-rats of one year and older, and briefly describe its anatomical context including markers of neuronal function (calbindin and parvalbumin. Solitary Cape mole-rats (Georychus capensis, social highveld mole-rats (Cryptomys hottentotus pretoriae, and eusocial naked mole-rats (Heterocephalus glaber were assessed. Compared to other rodents, the hippocampal formation in mole-rats is small, but shows a distinct cytoarchitecture in the dentate gyrus and CA1. Distributions of the calcium-binding proteins differ from those seen in rodents; e.g., calbindin in CA3 of naked mole-rats distributes similar to the pattern seen in early primate development, and calbindin staining extends into the stratum lacunosum-moleculare of Cape mole-rats. Proliferating cells and young neurons are found in low numbers in the hippocampus of all three mole-rat species. Resident granule cell numbers are low as well. Proliferating cells expressed as a percentage of resident granule cells are in the range of other rodents, while the percentage of young neurons is lower than that observed in surface dwelling rodents. Between mole-rat species, we observed no difference in the percentage of proliferating cells. The percentages of young neurons are high in social highveld and naked mole-rats, and low in solitary Cape mole-rats. The findings support that proliferation is regulated independently of average life expectancy and habitat. Instead, neuronal differentiation reflects species-specific demands, which appear lower in subterranean

  4. Adult neurogenesis and its anatomical context in the hippocampus of three mole-rat species.

    Science.gov (United States)

    Amrein, Irmgard; Becker, Anton S; Engler, Stefanie; Huang, Shih-Hui; Müller, Julian; Slomianka, Lutz; Oosthuizen, Maria K

    2014-01-01

    African mole-rats (family Bathyergidae) are small to medium sized, long-lived, and strictly subterranean rodents that became valuable animal models as a result of their longevity and diversity in social organization. The formation and integration of new hippocampal neurons in adult mammals (adult hippocampal neurogenesis, AHN) correlates negatively with age and positively with habitat complexity. Here we present quantitative data on AHN in wild-derived mole-rats of 1 year and older, and briefly describe its anatomical context including markers of neuronal function (calbindin and parvalbumin). Solitary Cape mole-rats (Georychus capensis), social highveld mole-rats (Cryptomys hottentotus pretoriae), and eusocial naked mole-rats (Heterocephalus glaber) were assessed. Compared to other rodents, the hippocampal formation in mole-rats is small, but shows a distinct cytoarchitecture in the dentate gyrus and CA1. Distributions of the calcium-binding proteins differ from those seen in rodents; e.g., calbindin in CA3 of naked mole-rats distributes similar to the pattern seen in early primate development, and calbindin staining extends into the stratum lacunosum-moleculare of Cape mole-rats. Proliferating cells and young neurons are found in low numbers in the hippocampus of all three mole-rat species. Resident granule cell numbers are low as well. Proliferating cells expressed as a percentage of resident granule cells are in the range of other rodents, while the percentage of young neurons is lower than that observed in surface dwelling rodents. Between mole-rat species, we observed no difference in the percentage of proliferating cells. The percentages of young neurons are high in social highveld and naked mole-rats, and low in solitary Cape mole-rats. The findings support that proliferation is regulated independently of average life expectancy and habitat. Instead, neuronal differentiation reflects species-specific demands, which appear lower in subterranean rodents.

  5. Radial glia in the proliferative ventricular zone of the embryonic and adult turtle, Trachemys scripta elegans.

    Science.gov (United States)

    Clinton, Brian K; Cunningham, Christopher L; Kriegstein, Arnold R; Noctor, Stephen C; Martínez-Cerdeño, Verónica

    2014-01-01

    To better understand the role of radial glial (RG) cells in the evolution of the mammalian cerebral cortex, we investigated the role of RG cells in the dorsal cortex and dorsal ventricular ridge of the turtle, Trachemys scripta elegans. Unlike mammals, the glial architecture of adult reptile consists mainly of ependymoradial glia, which share features with mammalian RG cells, and which may contribute to neurogenesis that continues throughout the lifespan of the turtle. To evaluate the morphology and proliferative capacity of ependymoradial glia (here referred to as RG cells) in the dorsal cortex of embryonic and adult turtle, we adapted the cortical electroporation technique, commonly used in rodents, to the turtle telencephalon. Here, we demonstrate the morphological and functional characteristics of RG cells in the developing turtle dorsal cortex. We show that cell division occurs both at the ventricle and away from the ventricle, that RG cells undergo division at the ventricle during neurogenic stages of development, and that mitotic Tbr2+ precursor cells, a hallmark of the mammalian SVZ, are present in the turtle cortex. In the adult turtle, we show that RG cells encompass a morphologically heterogeneous population, particularly in the subpallium where proliferation is most prevalent. One RG subtype is similar to RG cells in the developing mammalian cortex, while 2 other RG subtypes appear to be distinct from those seen in mammal. We propose that the different subtypes of RG cells in the adult turtle perform distinct functions.

  6. MiR-139-3p is related to left ventricular hypertrophy and cardiomyocyte apoptosis in two-kidney one-clip hypertensive rats

    Directory of Open Access Journals (Sweden)

    Yang Xiaomin

    2015-01-01

    Full Text Available MicroRNAs (miRNAs are important post-transcriptional regulators of gene expression in many physiological and pathological processes. Previous studies have reported the role of miR-139-3p in cancer. However, its specific roles and functions in the heart undergoing hypertrophy have yet to be fully elucidated. In the present study, a significant upregulation of miR-139-3p expression was demonstrated in the left ventricular myocardium of two-kidney one-clip (2K1C hypertensive rats using microarray and quantitative real-time PCR (qRT-PCR. Based on computational analysis, we observed that miR-139-3p can control the expression of mitogen-activated protein kinase 1 (MAPK1 as a target gene, which is essential for the induction of cardiac hypertrophy and cardiomyocyte apoptosis. This study provides first information that the highly expressed miR-139-3p might be closely involved in MAPK1-mediated cardiac hypertrophy and cardiomyocyte apoptotic processes in 2K1C rat.

  7. Neonatal tobacco smoke reduces thermogenesis capacity in brown adipose tissue in adult rats

    Directory of Open Access Journals (Sweden)

    T.C. Peixoto

    2018-04-01

    Full Text Available Maternal smoking is a risk factor for progeny obesity. We have previously shown, in a rat model of neonatal tobacco smoke exposure, a mild increase in food intake and a considerable increase in visceral adiposity in the adult offspring. Males also had secondary hyperthyroidism, while females had only higher T4. Since brown adipose tissue (BAT hypofunction is related to obesity, here we tested the hypothesis that higher levels of thyroid hormones are not functional in BAT, suggesting a lower metabolic rate. We evaluated autonomic nerve activity in BAT and its function in adult rats that were exposed to tobacco smoke during lactation. At birth, litters were adjusted to 3 male and 3 female pups/litter. From postnatal day (PND 3 to 21, Wistar lactating rats and their pups were divided into SE group, smoke-exposed in a cigarette smoking machine (4 times/day and C group, exposed to filtered air. Offspring were sacrificed at PND180. Adult SE rats of both genders had lower interscapular BAT autonomic nervous system activity, with higher BAT mass but no change in morphology. BAT UCP1 and CPT1a protein levels were decreased in the SE groups of both genders. Male SE rats had lower β3-AR, TRα1, and TRβ1 expression while females showed lower PGC1α expression. BAT Dio2 mRNA and hypothalamic POMC and MC4R levels were similar between groups. Hypothalamic pAMPK level was higher in SE males and lower in SE females. Thus, neonatal cigarette smoke exposure induces lower BAT thermogenic capacity, which can be obesogenic at adulthood.

  8. Neonatal tobacco smoke reduces thermogenesis capacity in brown adipose tissue in adult rats.

    Science.gov (United States)

    Peixoto, T C; Moura, E G; Oliveira, E; Younes-Rapozo, V; Soares, P N; Rodrigues, V S T; Santos, T R; Peixoto-Silva, N; Carvalho, J C; Calvino, C; Conceição, E P S; Guarda, D S; Claudio-Neto, S; Manhães, A C; Lisboa, P C

    2018-01-01

    Maternal smoking is a risk factor for progeny obesity. We have previously shown, in a rat model of neonatal tobacco smoke exposure, a mild increase in food intake and a considerable increase in visceral adiposity in the adult offspring. Males also had secondary hyperthyroidism, while females had only higher T4. Since brown adipose tissue (BAT) hypofunction is related to obesity, here we tested the hypothesis that higher levels of thyroid hormones are not functional in BAT, suggesting a lower metabolic rate. We evaluated autonomic nerve activity in BAT and its function in adult rats that were exposed to tobacco smoke during lactation. At birth, litters were adjusted to 3 male and 3 female pups/litter. From postnatal day (PND) 3 to 21, Wistar lactating rats and their pups were divided into SE group, smoke-exposed in a cigarette smoking machine (4 times/day) and C group, exposed to filtered air. Offspring were sacrificed at PND180. Adult SE rats of both genders had lower interscapular BAT autonomic nervous system activity, with higher BAT mass but no change in morphology. BAT UCP1 and CPT1a protein levels were decreased in the SE groups of both genders. Male SE rats had lower β3-AR, TRα1, and TRβ1 expression while females showed lower PGC1α expression. BAT Dio2 mRNA and hypothalamic POMC and MC4R levels were similar between groups. Hypothalamic pAMPK level was higher in SE males and lower in SE females. Thus, neonatal cigarette smoke exposure induces lower BAT thermogenic capacity, which can be obesogenic at adulthood.

  9. Effects of chronic fluoxetine treatment on neurogenesis and tryptophan hydroxylase expression in adolescent and adult rats.

    Science.gov (United States)

    Klomp, Anne; Václavů, Lena; Meerhoff, Gideon F; Reneman, Liesbeth; Lucassen, Paul J

    2014-01-01

    The antidepressant drug fluoxetine (Prozac) has been increasingly prescribed to children and adolescents with depressive disorders despite a lack of thorough understanding of its therapeutic effects in the paediatric population and of its putative neurodevelopmental effects. Within the framework of PRIOMEDCHILD ERA-NET, we investigated; a) effects of chronic fluoxetine treatment on adult hippocampal neurogenesis, a structural readout relevant for antidepressant action and hippocampal development; b) effects on tryptophan hydroxylase (TPH) expression, a measure of serotonin synthesis; c) whether treatment effects during adolescence differed from treatment at an adult age, and d) whether they were subregion-specific. Stereological quantification of the number of proliferating (Ki-67+) cells and of the number of young migratory neurons (doublecortin+), revealed a significant age-by-treatment interaction effect, indicating that fluoxetine affects both proliferation and neurogenesis in adolescent-treated rats differently than it does in adult-treated rats. In terms of subregional differences, fluoxetine enhanced proliferation mainly in the dorsal parts of the hippocampus, and neurogenesis in both the suprapyramidal and infrapyramidal blades of the dentate gyrus in adolescent-treated rats, while no such differences were seen in adult-treated rats. Fluoxetine exerted similar age-by-treatment interaction effects on TPH cells mainly in the ventral portion of the dorsal raphe nucleus. We conclude that fluoxetine exerts divergent effects on structural plasticity and serotonin synthesis in adolescent versus adult-treated rats. These preliminary data indicate a differential sensitivity of the adolescent brain to this drug and thus warrant further research into their behavioural and translational aspects. Together with recent related findings, they further call for caution in prescribing these drugs to the adolescent population.

  10. Effects of chronic fluoxetine treatment on neurogenesis and tryptophan hydroxylase expression in adolescent and adult rats.

    Directory of Open Access Journals (Sweden)

    Anne Klomp

    Full Text Available The antidepressant drug fluoxetine (Prozac has been increasingly prescribed to children and adolescents with depressive disorders despite a lack of thorough understanding of its therapeutic effects in the paediatric population and of its putative neurodevelopmental effects. Within the framework of PRIOMEDCHILD ERA-NET, we investigated; a effects of chronic fluoxetine treatment on adult hippocampal neurogenesis, a structural readout relevant for antidepressant action and hippocampal development; b effects on tryptophan hydroxylase (TPH expression, a measure of serotonin synthesis; c whether treatment effects during adolescence differed from treatment at an adult age, and d whether they were subregion-specific. Stereological quantification of the number of proliferating (Ki-67+ cells and of the number of young migratory neurons (doublecortin+, revealed a significant age-by-treatment interaction effect, indicating that fluoxetine affects both proliferation and neurogenesis in adolescent-treated rats differently than it does in adult-treated rats. In terms of subregional differences, fluoxetine enhanced proliferation mainly in the dorsal parts of the hippocampus, and neurogenesis in both the suprapyramidal and infrapyramidal blades of the dentate gyrus in adolescent-treated rats, while no such differences were seen in adult-treated rats. Fluoxetine exerted similar age-by-treatment interaction effects on TPH cells mainly in the ventral portion of the dorsal raphe nucleus. We conclude that fluoxetine exerts divergent effects on structural plasticity and serotonin synthesis in adolescent versus adult-treated rats. These preliminary data indicate a differential sensitivity of the adolescent brain to this drug and thus warrant further research into their behavioural and translational aspects. Together with recent related findings, they further call for caution in prescribing these drugs to the adolescent population.

  11. Cardiovascular magnetic resonance findings in a pediatric population with isolated left ventricular non-compaction

    Directory of Open Access Journals (Sweden)

    Uribe Sergio

    2012-01-01

    Full Text Available Abstract Background Isolated Left Ventricular Non-compaction (LVNC is an uncommon disorder characterized by the presence of increased trabeculations and deep intertrabecular recesses. In adults, it has been found that Ejection Fraction (EF decreases significantly as non-compaction severity increases. In children however, there are a few data describing the relation between anatomical characteristics of LVNC and ventricular function. We aimed to find correlations between morphological features and ventricular performance in children and young adolescents with LVNC using Cardiovascular Magnetic Resonance (CMR. Methods 15 children with LVNC (10 males, mean age 9.7 y.o., range 0.6 - 17 y.o., underwent a CMR scan. Different morphological measures such as the Compacted Myocardial Mass (CMM, Non-Compaction (NC to the Compaction (C distance ratio, Compacted Myocardial Area (CMA and Non-Compacted Myocardial Area (NCMA, distribution of NC, and the assessment of ventricular wall motion abnormalities were performed to investigate correlations with ventricular performance. EF was considered normal over 53%. Results The distribution of non-compaction in children was similar to published adult data with a predilection for apical, mid-inferior and mid-lateral segments. Five patients had systolic dysfunction with decreased EF. The number of affected segments was the strongest predictor of systolic dysfunction, all five patients had greater than 9 affected segments. Basal segments were less commonly affected but they were affected only in these five severe cases. Conclusion The segmental pattern of involvement of non-compaction in children is similar to that seen in adults. Systolic dysfunction in children is closely related to the number of affected segments.

  12. Measuring ventricular width on cranial computed tomography. Feasibility of dose reduction in a custom-made adult phantom

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    Daubner, D.; Cerhova, J.; Linn, J. [Dresden Univ. (Germany). Dept. of Neuroradiology; Spieth, S. [Dresden Univ. (Germany). Dept. of Radiology; Kirchhof, K. [Chemnitz Hospital (Germany). Dept. of Diagnostic and Interventional Radiology and Neuradiology

    2016-01-15

    To estimate feasible dose reduction to reliably measure ventricular width in adults with hydrocephalus in follow-up cranial computed tomography (CCT) using a custom-made phantom. A gelatine-filled adult calvarium with embedded central fibers of two carrots representing the lateral ventricles was used as a phantom. The phantom was scanned 11 times with two CT scanners (LightSpeed Ultra, GE and Somatom Sensation, Siemens), using tube currents of 380/400, 350, 300, 250, 200, 150 and 100 mA, and tube voltages of 140, 120, 100 and 80 kV. The width of the carrots was measured at four sites in consensus decision of two principle investigators blinded to the scan parameters. Values measured at 380/400 mA and 140 kV served as a reference for the width of the ventricles. Measurements received 1 point if they did not differ more than 0.5 mm from the reference values. A maximum score of 4 could be achieved. The relationship between the correct width measurement of the carrots (lateral ventricles) and the radiation dose can be described by a quadratic regression function. Pixel noise increases and accuracy of measurements decreases with a lower radiation dose. Starting from a tube current of 380/400 mA and a tube voltage of 140 kV, the dose can be reduced by 76 % for LightSpeed Ultra and by 80 % for Somatom Sensation provided that a margin of error of 37.5 % (score = 2.5) for correct width measurement of the carrots is accepted. Lowering the radiation dose by up to 48 % for LightSpeed Ultra and by 52 % for Somatom Sensation, compared to the standard protocol (120 kV and 400 mA) still allowed reliable measurements of ventricular widths in this model.

  13. Measuring ventricular width on cranial computed tomography. Feasibility of dose reduction in a custom-made adult phantom

    International Nuclear Information System (INIS)

    Daubner, D.; Cerhova, J.; Linn, J.; Spieth, S.; Kirchhof, K.

    2016-01-01

    To estimate feasible dose reduction to reliably measure ventricular width in adults with hydrocephalus in follow-up cranial computed tomography (CCT) using a custom-made phantom. A gelatine-filled adult calvarium with embedded central fibers of two carrots representing the lateral ventricles was used as a phantom. The phantom was scanned 11 times with two CT scanners (LightSpeed Ultra, GE and Somatom Sensation, Siemens), using tube currents of 380/400, 350, 300, 250, 200, 150 and 100 mA, and tube voltages of 140, 120, 100 and 80 kV. The width of the carrots was measured at four sites in consensus decision of two principle investigators blinded to the scan parameters. Values measured at 380/400 mA and 140 kV served as a reference for the width of the ventricles. Measurements received 1 point if they did not differ more than 0.5 mm from the reference values. A maximum score of 4 could be achieved. The relationship between the correct width measurement of the carrots (lateral ventricles) and the radiation dose can be described by a quadratic regression function. Pixel noise increases and accuracy of measurements decreases with a lower radiation dose. Starting from a tube current of 380/400 mA and a tube voltage of 140 kV, the dose can be reduced by 76 % for LightSpeed Ultra and by 80 % for Somatom Sensation provided that a margin of error of 37.5 % (score = 2.5) for correct width measurement of the carrots is accepted. Lowering the radiation dose by up to 48 % for LightSpeed Ultra and by 52 % for Somatom Sensation, compared to the standard protocol (120 kV and 400 mA) still allowed reliable measurements of ventricular widths in this model.

  14. Behavioral cross-sensitization between testosterone and fenproporex in adolescent and adult rats.

    Science.gov (United States)

    Conceição, C Q; Engi, S A; Cruz, F C; Planeta, C S

    2017-11-17

    The abuse of psychoactive drugs is considered a global health problem. During the last years, a relevant number of studies have investigated the relationship between anabolic-androgenic steroids (AAS) and other psychoactive drugs. AAS, such as testosterone, can cause a dependence syndrome that shares many features with the classical dependence to psychoactive substances. Pre-clinical evidence shows that there are interactions between testosterone and psychoactive drugs, such as cocaine. However, few studies have been performed to investigate the effect of repeated testosterone treatment on behavioral effects of amphetamine derivatives, such as fenproporex. The purpose of the present study was to investigate the effects of repeated testosterone administration on fenproporex-induced locomotor activity in adolescent and adult rats. Adolescent male Wistar rats were injected with testosterone (10 mg/kg sc for 10 days). After 3 days, animals received an acute injection of fenproporex (3.0 mg/kg ip) and the locomotor activity was recorded during 40 min. Thirty days later, the same animals received the same treatment with testosterone followed by a fenproporex challenge injection as described above. Our results demonstrated that repeated testosterone induced behavioral sensitization to fenproporex in adolescent but not in adult rats. These findings suggest that repeated AAS treatment might increase the dependence vulnerability to amphetamine and its derivatives in adolescent rats.

  15. Early Effects of a Low Fat, Fructose-Rich Diet on Liver Metabolism, Insulin Signaling, and Oxidative Stress in Young and Adult Rats

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    Raffaella Crescenzo

    2018-04-01

    Full Text Available The increase in the use of refined food, which is rich in fructose, is of particular concern in children and adolescents, since the total caloric intake and the prevalence of metabolic syndrome are increasing continuously in these populations. Nevertheless, the effects of high fructose diet have been mostly investigated in adults, by focusing on the effect of a long-term fructose intake. Notably, some reports evidenced that even short-term fructose intake exerts detrimental effects on metabolism. Therefore, the aim of this study was to compare the metabolic changes induced by the fructose-rich diet in rats of different age, i.e., young (30 days old and adult (90 days old rats. The fructose-rich diet increased whole body lipid content in adult, but not in young rats. The analysis of liver markers of inflammation suggests that different mechanisms depending on the age might be activated after the fructose-rich diet. In fact, a pro-inflammatory gene-expression analysis showed just a minor activation of macrophages in young rats compared to adult rats, while other markers of low-grade metabolic inflammation (TNF-alpha, myeloperoxidase, lipocalin, haptoglobin significantly increased. Inflammation was associated with oxidative damage to hepatic lipids in young and adult rats, while increased levels of hepatic nitrotyrosine and ceramides were detected only in young rats. Interestingly, fructose-induced hepatic insulin resistance was evident in young but not in adult rats, while whole body insulin sensitivity decreased both in fructose-fed young and adult rats. Taken together, the present data indicate that young rats do not increase their body lipids but are exposed to metabolic perturbations, such as hepatic insulin resistance and hepatic oxidative stress, in line with the finding that increased fructose intake may be an important predictor of metabolic risk in young people, independently of weight status. These results indicate the need of corrective

  16. Adult naked mole-rat brain retains the NMDA receptor subunit GluN2D associated with hypoxia tolerance in neonatal mammals.

    Science.gov (United States)

    Peterson, Bethany L; Park, Thomas J; Larson, John

    2012-01-11

    Adult naked mole-rats show a number of systemic adaptations to a crowded underground habitat that is low in oxygen and high in carbon dioxide. Remarkably, brain slice tissue from adult naked mole-rats also is extremely tolerant to oxygen deprivation as indicated by maintenance of synaptic transmission under hypoxic conditions as well as by a delayed neuronal depolarization during anoxia. These characteristics resemble hypoxia tolerance in brain slices from neonates in a variety of mammal species. An important component of neonatal tolerance to hypoxia involves the subunit composition of NMDA receptors. Neonates have a high proportion of NMDA receptors with GluN2D subunits which are protective because they retard calcium entry into neurons during hypoxic episodes. Therefore, we hypothesized that adult naked mole-rats retain a protective, neonatal-like, NMDA receptor subunit profile. We used immunoblotting to assess age-related changes in NMDA receptor subunits in naked mole-rats and mice. The results show that adult naked mole-rat brain retains a much greater proportion of the hypoxia-protective GluN2D subunit compared to adult mice. However, age-related changes in other subunits (GluN2A and GluN2B) from the neonatal period to adulthood were comparable in mice and naked mole-rats. Hence, adult naked mole-rat brain only retains the neonatal NMDA receptor subunit that is associated with hypoxia tolerance. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  17. A comparative study on the effect of high cholesterol diet on the hippocampal CA1 area of adult and aged rats.

    Science.gov (United States)

    Abo El-Khair, Doaa M; El-Safti, Fatma El-Nabawia A; Nooh, Hanaa Z; El-Mehi, Abeer E

    2014-06-01

    Dementia is one of the most important problems nowadays. Aging is associated with learning and memory impairments. Diet rich in cholesterol has been shown to be detrimental to cognitive performance. This work was carried out to compare the effect of high cholesterol diet on the hippocampus of adult and aged male albino rats. Twenty adult and twenty aged male rats were used in this study. According to age, the rats were randomly subdivided into balanced and high cholesterol diet fed groups. The diet was 15 g/rat/day for adult rats and 20 g/rat/day for aged rats for eight weeks. Serial coronal sections of hippocampus and blood samples were taken from each rat. For diet effect evaluation, Clinical, biochemical, histological, immunohistochemical, and morphometric assessments were done. In compare to a balanced diet fed rat, examination of Cornu Ammonis 1 (CA 1) area in the hippocampus of the high cholesterol diet adult rats showed degeneration, a significant decrease of the pyramidal cells, attenuation and/or thickening of small blood vessels, apparent increase of astrocytes and apparent decrease of Nissl's granules content. Moreover, the high cholesterol diet aged rats showed aggravation of senility changes of the hippocampus together with Alzheimer like pathological changes. In conclusion, the high cholesterol diet has a significant detrimental effect on the hippocampus and aging might pronounce this effect. So, we should direct our attention to limit cholesterol intake in our food to maintain a healthy life style for a successful aging.

  18. Risk of Ventricular Arrhythmia with Citalopram and Escitalopram: A Population-Based Study.

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    Elena Qirjazi

    Full Text Available The risk of ventricular arrhythmia with citalopram and escitalopram is controversial. In this study we investigated the association between these two drugs and the risk of ventricular arrhythmia.We conducted a population-based retrospective cohort study of older adults (mean age 76 years from 2002 to 2012 in Ontario, Canada, newly prescribed citalopram (n = 137 701 or escitalopram (n = 38 436, compared to those prescribed referent antidepressants sertraline or paroxetine (n = 96 620. After inverse probability of treatment weighting using a propensity score, the baseline characteristics of the comparison groups were similar. The primary outcome was a hospital encounter with ventricular arrhythmia within 90 days of a new prescription, assessed using hospital diagnostic codes. The secondary outcome was all-cause mortality within 90 days.Citalopram was associated with a higher risk of a hospital encounter with ventricular arrhythmia compared with referent antidepressants (0.06% vs. 0.04%, relative risk [RR] 1.53, 95% confidence intervals [CI]1.03 to 2.29, and a higher risk of mortality (3.49% vs. 3.12%, RR 1.12, 95% CI 1.06 to 1.18. Escitalopram was not associated with a higher risk of ventricular arrhythmia compared with the referent antidepressants (0.03% vs. 0.04%, RR 0.84, 95% CI 0.42 to 1.68, but was associated with a higher risk of mortality (2.86% vs. 2.63%, RR 1.09, 95% CI 1.01 to 1.18.Among older adults, initiation of citalopram compared to two referent antidepressants was associated with a small but statistically significant increase in the 90-day risk of a hospital encounter for ventricular arrhythmia.

  19. Risk of Ventricular Arrhythmia with Citalopram and Escitalopram: A Population-Based Study.

    Science.gov (United States)

    Qirjazi, Elena; McArthur, Eric; Nash, Danielle M; Dixon, Stephanie N; Weir, Matthew A; Vasudev, Akshya; Jandoc, Racquel; Gula, Lorne J; Oliver, Matthew J; Wald, Ron; Garg, Amit X

    2016-01-01

    The risk of ventricular arrhythmia with citalopram and escitalopram is controversial. In this study we investigated the association between these two drugs and the risk of ventricular arrhythmia. We conducted a population-based retrospective cohort study of older adults (mean age 76 years) from 2002 to 2012 in Ontario, Canada, newly prescribed citalopram (n = 137 701) or escitalopram (n = 38 436), compared to those prescribed referent antidepressants sertraline or paroxetine (n = 96 620). After inverse probability of treatment weighting using a propensity score, the baseline characteristics of the comparison groups were similar. The primary outcome was a hospital encounter with ventricular arrhythmia within 90 days of a new prescription, assessed using hospital diagnostic codes. The secondary outcome was all-cause mortality within 90 days. Citalopram was associated with a higher risk of a hospital encounter with ventricular arrhythmia compared with referent antidepressants (0.06% vs. 0.04%, relative risk [RR] 1.53, 95% confidence intervals [CI]1.03 to 2.29), and a higher risk of mortality (3.49% vs. 3.12%, RR 1.12, 95% CI 1.06 to 1.18). Escitalopram was not associated with a higher risk of ventricular arrhythmia compared with the referent antidepressants (0.03% vs. 0.04%, RR 0.84, 95% CI 0.42 to 1.68), but was associated with a higher risk of mortality (2.86% vs. 2.63%, RR 1.09, 95% CI 1.01 to 1.18). Among older adults, initiation of citalopram compared to two referent antidepressants was associated with a small but statistically significant increase in the 90-day risk of a hospital encounter for ventricular arrhythmia.

  20. Chronic heart failure modifies respiratory mechanics in rats: a randomized controlled trial

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    Deise M. Pacheco

    2016-01-01

    Full Text Available ABSTRACT Objective To analyze respiratory mechanics and hemodynamic alterations in an experimental model of chronic heart failure (CHF following myocardial infarction. Method Twenty-seven male adult Wistar rats were randomized to CHF group (n=12 or Sham group (n=15. Ten weeks after coronary ligation or sham surgery, the animals were anesthetized and submitted to respiratory mechanics and hemodynamic measurements. Pulmonary edema as well as cardiac remodeling were measured. Results The CHF rats showed pulmonary edema 26% higher than the Sham group. The respiratory system compliance (Crs and the total lung capacity (TLC were lower (40% and 27%, respectively in the CHF rats when compared to the Sham group (P<0.01. There was also an increase in tissue resistance (Gti and elastance (Hti (28% and 45%, respectively in the CHF group. Moreover, left ventricular end-diastolic pressure was higher (32 mmHg vs 4 mmHg, P<0.01, while the left ventricular systolic pressure was lower (118 mmHg vs 130 mmHg, P=0.02 in the CHF group when compared to the control. Pearson’s correlation coefficient showed a negative association between pulmonary edema and Crs (r=–0.70, P=0.0001 and between pulmonary edema and TLC (r=–0.67,P=0.0034. Pulmonary edema correlated positively with Gti (r=0.68, P=0.001 and Hti (r=0.68, P=0.001. Finally, there was a strong positive relationship between pulmonary edema and heart weight (r=0.80, P=0.001. Conclusion Rats with CHF present important changes in hemodynamic and respiratory mechanics, which may be associated with alterations in cardiopulmonary interactions.

  1. Reorganization of auditory map and pitch discrimination in adult rats chronically exposed to low-level ambient noise

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    Weimin eZheng

    2012-09-01

    Full Text Available Behavioral adaption to a changing environment is critical for an animal’s survival. How well the brain can modify its functional properties based on experience essentially defines the limits of behavioral adaptation. In adult animals the extent to which experience shapes brain function has not been fully explored. Moreover, the perceptual consequences of experience-induced changes in the brains of adults remain unknown. Here we show that the tonotopic map in the primary auditory cortex of adult rats living with low-level ambient noise underwent a dramatic reorganization. Behaviorally, chronic noise-exposure impaired fine, but not coarse pitch discrimination. When tested in a noisy environment, the noise-exposed rats performed as well as in a quiet environment whereas the control rats performed poorly. This suggests that noise-exposed animals had adapted to living in a noisy environment. Behavioral pattern analyses revealed that stress or distraction engendered by the noisy background could not account for the poor performance of the control rats in a noisy environment. A reorganized auditory map may therefore have served as the neural substrate for the consistent performance of the noise-exposed rats in a noisy environment.

  2. Effects of cannabidiol on contractions and calcium signaling in rat ventricular myocytes.

    Science.gov (United States)

    Ali, Ramez M; Al Kury, Lina T; Yang, Keun-Hang Susan; Qureshi, Anwar; Rajesh, Mohanraj; Galadari, Sehamuddin; Shuba, Yaroslav M; Howarth, Frank Christopher; Oz, Murat

    2015-04-01

    Cannabidiol (CBD), a major nonpsychotropic cannabinoid found in Cannabis plant, has been shown to influence cardiovascular functions under various physiological and pathological conditions. In the present study, the effects of CBD on contractility and electrophysiological properties of rat ventricular myocytes were investigated. Video edge detection was used to measure myocyte shortening. Intracellular Ca(2+) was measured in cells loaded with the Ca(2+) sensitive fluorescent indicator fura-2 AM. Whole-cell patch clamp was used to measure action potential and Ca(2+) currents. Radioligand binding was employed to study pharmacological characteristics of CBD binding. CBD (1μM) caused a significant decrease in the amplitudes of electrically evoked myocyte shortening and Ca(2+) transients. However, the amplitudes of caffeine-evoked Ca(2+) transients and the rate of recovery of electrically evoked Ca(2+) transients following caffeine application were not altered. CBD (1μM) significantly decreased the duration of APs. Further studies on L-type Ca(2+) channels indicated that CBD inhibits these channels with IC50 of 0.1μM in a voltage-independent manner. Radioligand studies indicated that the specific binding of [(3)H]Isradipine, was not altered significantly by CBD. The results suggest that CBD depresses myocyte contractility by suppressing L-type Ca(2+) channels at a site different than dihydropyridine binding site and inhibits excitation-contraction coupling in cardiomyocytes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Effects of dimethylarsinic and dimethylarsinous acid on evoked synaptic potentials in hippocampal slices of young and adult rats

    International Nuclear Information System (INIS)

    Krueger, Katharina; Repges, Hendrik; Hippler, Joerg; Hartmann, Louise M.; Hirner, Alfred V.; Straub, Heidrun; Binding, Norbert; Musshoff, Ulrich

    2007-01-01

    In this study, the effects of pentavalent dimethylarsinic acid ((CH 3 ) 2 AsO(OH); DMA V ) and trivalent dimethylarsinous acid ((CH 3 ) 2 As(OH); DMA III ) on synaptic transmission generated by the excitatory Schaffer collateral-CA1 synapse were tested in hippocampal slices of young (14-21 day-old) and adult (2-4 month-old) rats. Both compounds were applied in concentrations of 1 to 100 μmol/l. DMA V had no effect on the amplitudes of evoked fEPSPs or the induction of LTP recorded from the CA1 dendritic region either in adult or in young rats. However, application of DMA III significantly reduced the amplitudes of evoked fEPSPs in a concentration-dependent manner with a total depression following application of 100 μmol/l DMA III in adult and 10 μmol/l DMA III in young rats. Moreover, DMA III significantly affected the LTP-induction. Application of 10 μmol/l DMA III resulted in a complete failure of the postsynaptic potentiation of the fEPSP amplitudes in slices taken both from adult and young rats. The depressant effect was not reversible after a 30-min washout of the DMA III . In slices of young rats, the depressant effects of DMA III were more pronounced than in those taken from adult ones. Compared to the (absent) effect of DMA V on synaptic transmission, the trivalent compound possesses a considerably higher neurotoxic potential

  4. Synergistic effect of estradiol and fluoxetine in young adult and middle-aged female rats in two models of experimental depression.

    Science.gov (United States)

    Récamier-Carballo, Soledad; Estrada-Camarena, Erika; Reyes, Rebeca; Fernández-Guasti, Alonso

    2012-08-01

    The antidepressant effect of estrogens combined with antidepressants is controversial: some preclinical data showed that estrogens facilitate the effect of antidepressants in the forced swimming test (FST) in young adult rats, while others failed to find such effect in middle-aged rats in the chronic mild stress (CMS) model. In clinics similar differences were reported and may be due to the compounds, the depression model or type of depression, the experimental design, and the age of the subjects or the women's menopause stage. The objective of this study was to analyze the antidepressant-like effect of the combination of 17β-estradiol (E(2)) and fluoxetine (FLX) in young adults (2-4 months) and middle-aged (12-14 months) ovariectomized (OVX) rats in two experimental models: FST and CMS. E(2) (5 and 10 μg/rat) and FLX (2.5 and 10 mg/kg) per se dose-dependently reduced immobility in both age groups and, in young adults both compounds increased swimming, whereas in middle-aged rats they increased swimming and climbing. Analysis of the antidepressant-like effect of the combination of suboptimal doses of FLX (1.25 mg/kg) and E(2) (2.5 μg/rat) showed a decrease in immobility and an increase in swimming in both age groups. In the CMS, chronic E(2) (2.5 μg/rat) with FLX (1.25 mg/kg) augmented relative sucrose intake, but middle-aged rats responded 2 weeks earlier than young adults. These results show that the antidepressant-like effect of the combination of E(2) and FLX in young adult and middle-aged female rats is evidenced in the two animal models of depression: FST and CMS. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. The expression of NFATc1 in adult rat skeletal muscle fibres.

    Science.gov (United States)

    Mutungi, Gabriel

    2008-03-01

    Although numerous studies have recently implicated the calcineurin-nuclear factor of activated T-cells (Cn-NFAT) signalling pathway in the regulation of activity-dependent fibre type switching in adult mammalian skeletal muscles, little is known about the endogenous expression of NFAT proteins in the various fibre types present in these muscles. In this study, the immunolocalization of NFATc1 (also known as NFATc or NFAT2) in the extensor digitorum longus (EDL; a mainly fast-twitch muscle) and the soleus (a predominantly slow-twitch muscle) muscles of adult ( approximately 90-day-old) Wistar rats was investigated. The results show that NFATc1 is expressed only in oxidative fibres (i.e. type I and type IIA fibres) that stain intensely for succinate dehydrogenase activity irrespective of whether they are from the fast- or slow-twitch muscle. Thus, 99 +/- 4% (n = 7 rats) of the muscle fibres in the soleus and 42 +/- 2% (n = 7 rats) of those in the EDL expressed NFATc1. In the soleus muscle fibres, NFATc1 was localized mainly in the fibre nuclei, whereas in the EDL fibres it was localized in both the cytoplasm and the nuclei. However, no difference in its localization was observed between type I and type IIA fibres in both muscles. Western blot experiments showed that the soleus expressed more NFATc1 proteins than the EDL. From these results, we suggest that NFATc1 controls the number and distribution of both type I and type IIA fibres, as well as the oxidative capacity of adult mammalian skeletal muscles.

  6. Dobutamine stress echocardiography in healthy adult male rats

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    Couet Jacques

    2005-10-01

    Full Text Available Abstract Background Dobutamine stress echocardiography is used to investigate a wide variety of heart diseases in humans. Dobutamine stress echocardiography has also been used in animal models of heart disease despite the facts that the normal response of healthy rat hearts to this type of pharmacological stress testing is unknown. This study was performed to assess this normal response. Methods 15 normal adult male Wistar rats were evaluated. Increasing doses of dobutamine were infused intravenously under continuous imaging of the heart by a 12 MHz ultrasound probe. Results Dobutamine stress echocardiography reduced gradually LV diastolic and systolic dimensions. Ejection fraction increased by a mean of +24% vs. baseline. Heart rate increased progressively without reaching a plateau. Changes in LV dimensions and ejection fraction reached a plateau after a mean of 4 minutes at a constant infusion rate. Conclusion DSE can be easily performed in rats. The normal response is an increase in heart rate and ejection fraction and a decrease in LV dimensions. A plateau in echocardiographic measurements is obtained after 4 minutes of a constant infusion rate in most animals.

  7. Surgical ablation of ventricular tachycardia secondary to congenital ventricular septal aneurysm.

    Science.gov (United States)

    Graffigna, A; Minzioni, G; Ressia, L; Vigano, M

    1994-04-01

    Three patients underwent surgical ablation for ventricular tachycardia resulting from an aneurysm of the membranous portion of the ventricular septum. Two patients had a definite history of cardiac murmur during infancy, and one of them was found at the time of operation to have a left-to-right shunt through the apex of the aneurysm. The earliest ventricular activation sites were located around the neck of the aneurysm and were ablated in 1 patient by encircling the endocardial ventriculotomy and by cryoablation in the remaining 2. After focus resection had been completed, aneurysm resection and ventricular septal reconstruction were performed. All patients were alive and free of ventricular tachycardia and did not need medication as of 61, 66, and 88 months postoperatively. Spontaneous closure of a ventricular septal defect may lead to the formation of an aneurysm in the ventricular septum that may sustain ventricular tachycardias. Such arrhythmias can be effectively treated using electrically guided surgical techniques.

  8. Histiocytoid cardiomyopathy and ventricular noncompaction presenting as sudden death in an adult male.

    Science.gov (United States)

    Val-Bernal, J Fernando; Mayorga, Marta; Ortega, Clara; Linares, Emma

    2017-11-01

    Histiocytoid/oncocytic cardiomyopathy (HCM) is a rare, distinctive arrhythmogenic disorder that presents as arrhythmia or sudden death in infants and children. Ventricular noncompaction (VNC) is a rare cardiomyopathy characterized by a thickened endocardial layer of noncompacted myocardium and a thin epicardial layer of compacted myocardium. Only six cases of the association of both cardiomyopathies have been reported previously in the literature. All these cases were in children. To the best of our knowledge, a case of HCM has not been described in the adult. We report the case of a 45-year-old man with an increased heart weight and involvement of both ventricles by HCM and VNC cardiomyopathy. Besides, multiple foci of myocardial disorganization were detected. He died suddenly while hiking. The association of both processes HCM and VNC was an unexpected finding at autopsy. The death was linked to functional abnormalities of the cardiac histiocytoid cells, and it was favored by a state of abnormal development of the heart. Copyright © 2017 Elsevier GmbH. All rights reserved.

  9. Use of the light/dark test for anxiety in adult and adolescent male rats.

    Science.gov (United States)

    Arrant, Andrew E; Schramm-Sapyta, Nicole L; Kuhn, Cynthia M

    2013-11-01

    The light/dark (LD) test is a commonly used rodent test of unconditioned anxiety-like behavior that is based on an approach/avoidance conflict between the drive to explore novel areas and an aversion to brightly lit, open spaces. We used the LD test to investigate developmental differences in behavior between adolescent (postnatal day (PN) 28-34) and adult (PN67-74) male rats. We investigated whether LD behavioral measures reflect anxiety-like behavior similarly in each age group using factor analysis and multiple regression. These analyses showed that time in the light compartment, percent distance in the light, rearing, and latency to emerge into the light compartment were measures of anxiety-like behavior in each age group, while total distance traveled and distance in the dark compartment provided indices of locomotor activity. We then used these measures to assess developmental differences in baseline LD behavior and the response to anxiogenic drugs. Adolescent rats emerged into the light compartment more quickly than adults and made fewer pokes into the light compartment. These age differences could reflect greater risk taking and less risk assessment in adolescent rats than adults. Adolescent rats were less sensitive than adults to the anxiogenic effects of the benzodiazepine inverse agonist N-methyl-β-carboline-3-carboxamide (FG-7142) and the α₂ adrenergic antagonist yohimbine on anxiety-like behaviors validated by factor analysis, but locomotor variables were similarly affected. These data support the results of the factor analysis and indicate that GABAergic and noradrenergic modulation of LD anxiety-like behavior may be immature during adolescence. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Abstinence environment contributes to age differences in reinstatement of cocaine seeking between adolescent and adult male rats.

    Science.gov (United States)

    Li, Chen; Frantz, Kyle J

    2017-07-01

    Extinction responding and cue-induced reinstatement of cocaine seeking after 60-days of forced abstinence are attenuated in male rats that self-administered cocaine during adolescence, compared with adults. Given that environmental enrichment during abstinence decreases reinstatement among adults, a possible explanation for attenuated reinstatement among adolescents is that standard pair-housing in prior studies creates a more stimulating environment for younger rats. Therefore, we tested whether standard pair-housing is necessary for the attenuated reinstatement among adolescents by determining whether an impoverished environment during abstinence would increase reinstatement among adolescents, up to adult levels. Conversely, we also tested whether environmental enrichment could further decrease reinstatement among adolescents, and whether we could replicate effects of environmental enrichment to decrease reinstatement among adults down to adolescent levels (positive controls). Adolescent and adult male Wistar rats self-administered cocaine intravenously for 12days (fixed ratio 1; 0.36mg/kg per infusion; 2h sessions). Rats were then moved into enriched (grouped, large cages, novel toys), standard (pair-housed, shoebox cages), or impoverished (isolated, hanging cages) housing conditions. After 60days, extinction and cue-induced reinstatement of cocaine seeking were tested, followed by drug-primed reinstatement (0, 5, 10mg/kg cocaine, i.p.). Consistent with previous results, extinction and cue-induced reinstatement were attenuated in adolescent-onset groups compared with adults; this age difference also extended to drug-primed reinstatement. In support of the present hypothesis, an impoverished environment during abstinence increased reinstatement among adolescents to levels that were not different from adult standard-housing levels. These data suggest that abstinence environment influences the enduring effects of cocaine among adolescents as well as adults

  11. Effects of monomethylarsonic and monomethylarsonous acid on evoked synaptic potentials in hippocampal slices of adult and young rats

    International Nuclear Information System (INIS)

    Krueger, Katharina; Straub, Heidrun; Hirner, Alfred V.; Hippler, Joerg; Binding, Norbert; Musshoff, Ulrich

    2009-01-01

    Arsenite and its metabolites, dimethylarsinic or dimethylarsinous acid, have previously been shown to disturb synaptic transmission in hippocampal slices of rats (Krueger, K., Gruner, J., Madeja, M., Hartmann, L.M., Hirner, A.V., Binding, N., Muβhoff, U., 2006a. Blockade and enhancement of glutamate receptor responses in Xenopus oocytes by methylated arsenicals. Arch. Toxicol. 80, 492-501, Krueger, K., Straub, H., Binding, N., Muβhoff, U., 2006b. Effects of arsenite on long-term potentiation in hippocampal slices from adult and young rats. Toxicol. Lett. 165, 167-173, Krueger, K., Repges, H., Hippler, J., Hartmann, L.M., Hirner, A.V., Straub, H., Binding, N., Muβhoff, U., 2007. Effects of dimethylarsinic and dimethylarsinous acid on evoked synaptic potentials in hippocampal slices of young and adult rats. Toxicol. Appl. Pharmacol. 225, 40-46). The present experiments investigate, whether the important arsenic metabolites monomethylarsonic acid (MMA V ) and monomethylarsonous acid (MMA III ) also influence the synaptic functions of the hippocampus. In hippocampal slices of young (14-21 days-old) and adult (2-4 months-old) rats, evoked synaptic field potentials from the Schaffer collateral-CA1 synapse were measured under control conditions and during and after 30 and 60 min of application of the arsenic compounds. MMA V had no effect on the synapse functions neither in slices of adult nor in those from young rats. However, MMA III strongly influenced the synaptic transmission: it totally depressed the amplitudes of fEPSPs at concentrations of 50 μmol/l (adult rats) and 25 μmol/l (young rats) and LTP amplitudes at concentrations of 25 μmol/l (adult rats) and 10 μmol/l (young rats), respectively. In contrast, application of 1 μmol/l MMA III led to an enhancement of the LTP amplitude in young rats, which is interpretable by an enhancing effect on NMDA receptors and a lack of the blocking effect on AMPA receptors at this concentration (Krueger, K., Gruner, J

  12. HISTOLOGICAL STUDIES OF THE EFFECTS OF RED PEPPER ON THE STOMACH OF ADULT WISTAR RATS

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    Josiah O. Adjene

    2007-01-01

    Full Text Available Histological effects of red pepper commonly used as spice in food on the stomach of adult wistar rats were carefully investigated. The rats of both sexes (n=24, average weight of 200g were randomly assigned into two treatments (n=16 and control (n=6 groups. The rats in the treatments groups received 1g and 2g of red pepper thoroughly mixed with 20g of their feeds for 7 and 14 days, while the control rats received equal amounts of feeds without the red pepper added. The rats were fed with grower's mash purchased from Edo feeds and flour mill Ltd, Ewu, Edo State and were given water liberally. The rats were sacrificed on day eight and fifteen of the experiment respectively.The stomach was carefully dissected out and quickly fixed in 10% formol saline for routine histological procedure after H & E method.The histological findings after H&E methods indicated that the treated sections of the stomach showed some level of cellular hypertrophy, congestion of blood vessels degenerative changes disruption and distortion of the cytoarchitecture of the stomach.These findings indicate that red pepper may have some deleterious effects on the microanatomy of the stomach of adult wistar rat at higher doses. It is recommended that further studies aimed at corroborating these findings be carried out.

  13. Behavioral cross-sensitization between testosterone and fenproporex in adolescent and adult rats

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    C.Q. Conceição

    2017-11-01

    Full Text Available The abuse of psychoactive drugs is considered a global health problem. During the last years, a relevant number of studies have investigated the relationship between anabolic-androgenic steroids (AAS and other psychoactive drugs. AAS, such as testosterone, can cause a dependence syndrome that shares many features with the classical dependence to psychoactive substances. Pre-clinical evidence shows that there are interactions between testosterone and psychoactive drugs, such as cocaine. However, few studies have been performed to investigate the effect of repeated testosterone treatment on behavioral effects of amphetamine derivatives, such as fenproporex. The purpose of the present study was to investigate the effects of repeated testosterone administration on fenproporex-induced locomotor activity in adolescent and adult rats. Adolescent male Wistar rats were injected with testosterone (10 mg/kg sc for 10 days. After 3 days, animals received an acute injection of fenproporex (3.0 mg/kg ip and the locomotor activity was recorded during 40 min. Thirty days later, the same animals received the same treatment with testosterone followed by a fenproporex challenge injection as described above. Our results demonstrated that repeated testosterone induced behavioral sensitization to fenproporex in adolescent but not in adult rats. These findings suggest that repeated AAS treatment might increase the dependence vulnerability to amphetamine and its derivatives in adolescent rats.

  14. Effect of Tumor Necrosis Factor-α on Neutralization of Ventricular Fibrillation in Rats with Acute Myocardial Infarction

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    Yu Chen

    2011-01-01

    Full Text Available The purpose of this study was to explore the effects of tumor necrosis factor-α (TNF-α on ventricular fibrillation (VF in rats with acute myocardial infarction (AMI. Rats were randomly classified into AMI group, sham operation group and recombinant human tumor necrosis factor receptor:Fc fusion protein (rhTNFR:Fc group. Spontaneous and induced VFs were recorded. Monophasic action potentials (MAPs among different zones of myocardium were recorded at eight time points before and after ligation and MAP duration dispersions (MAPDds were calculated. Then expression of TNF-α among different myocardial zones was detected. After ligation of the left anterior descending coronary artery, total TNF-α expression in AMI group began to markedly increase at 10 min, reached a climax at 20–30min, and then gradually decreased. The time-windows of VFs and MAPDds in the border zone performed in a similar way. At the same time-point, the expression of TNF-α in the ischemia zone was greater than that in the border zone, and little in the non-ischemia zone. Although the time windows of TNF-α expression, the MAPDds in the border zone and the occurrence of VFs in the rhTNFR:Fc group were similar to those in the AMI group, they all decreased in the rhTNFR:Fc group. Our findings demonstrate that TNF-α could enlarge the MAPDds in the border zone, and promote the onset of VFs.

  15. Preconception paternal bisphenol A exposure induces sex-specific anxiety and depression behaviors in adult rats.

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    Ying Fan

    Full Text Available Bisphenol A (BPA, an environmental endocrine-disrupting compound, has drawn a great attention for its adverse effect on behavioral development. Maternal exposure to this compound has been reported to induce anxiety and depression in offspring, but the effect of its paternal exposure is rarely discussed. This study investigated whether preconception paternal BPA exposure can affect the emotions of male rats and their offspring. Eighteen adult male rats (F0 received either a vehicle or 50 μg/kg/day BPA diet for 21 weeks and were then mated with non-exposed females to produce offspring (F1. The affective behaviors of F0 and F1 rats were evaluated in the open-field test, the elevated-plus maze and the forced swimming test, and their serum corticosterone were then examined. BPA exposure induced increased anxiety behaviors along with increased serum corticosterone in F0 rats. This paternal exposure also led to increased anxiety behaviors in F1 females and aggravated depression behaviors in both sexes of F1 rats. Furthermore, only F1 females exhibited increased serum corticosterone. Overall, these data indicate that preconception paternal exposure to a low dose of BPA may induce transgenerational sex-specific impairments in the affection of adult rats.

  16. Protective effects of valsartan and benazepril combined with atorvastatin on cardiorenal syndrome in rats.

    Science.gov (United States)

    Tang, S-Y; Peng, D-F; Hu, Y-J; Chen, J

    2015-01-01

    To study the protective effects of valsartan (Val) and benazepril, (Ben) combined with atorvastatin (Ato), on cardiorenal syndrome (CRS) in rats. After establishing cardiorenal syndrome model, the rats were randomly divided into control, Ato, Ben+Ato and Val+Ato groups, which were treated with corresponding drugs. Before and 4 weeks after treatment, the serum creatinine (Scr), blood urea nitrogen (BUN), type-B natriuretic peptide (BNP), aldosterone (ALD), angiotensin (Ang) II, C-reactive protein (CRP), blood lipid and urine protein were determined. The left ventricular systolic pressure (LVSP), left ventricular diastolic pressure (LVDP), left ventricular end-diastolic pressure (LVEDP) as well as maximum rising and falling rates of left ventricular pressure (±dp/dtmax) were detected. The heart weight index was also determined. 6, 3, 1 and 2 rats control, Ato, Ben+Ato and Val+Ato groups died, respectively. Compared with control group, the serum Cr, BUN, BNP, ALD, CRP and urinary protein levels in treatment groups significantly decreased, and the blood lipid level, LVDP, LVEDP and heart weight index significantly decreased, with increased LVSP. No statistically significant difference was observed among treatment groups. Valsartan and benazepril, combined with atorvastatin, can have significant protective effects on cardiorenal functions of rats with CRS, with no significant difference between these two drugs.

  17. Effects of amphetamine administration on neurogenesis in adult rats

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    Tomasz Stępień

    2017-12-01

    Full Text Available In our study expression of phospho-(Ser-10-histone H3 (pH3S10, a marker for the early stage of neurogenesis, and cellular early response genes were investigated using c-Fos protein as an example of a transcription factor in the neurogenic process in rats. Neurogenesis in the adult brain is regulated by endo- and exogenous factors, which influence the proliferation potential of progenitor cells and accelerate the dendritic development of newborn neurons. D-amphetamine, a psychoactive substance, is one of the exogenous factors able to influence the process of neurogenesis. The rats were injected with D-amphetamine at a dose of 1.5 mg/kg/body weight (b.w. under one administration scheme. Analysis of the pH3S10 and c-Fos expression levels in the group of D-amphetamine administered rats provided evidence of enhanced expression of these proteins in the regions of neurogenesis occurrence in rats. However, conclusions concerning stimulant effects of amphetamine on neurogenesis should be formulated with great caution, taking into account amphetamine dosage and the administration scheme. It should also be remembered that doses of psychoactive substances used in animal models can be lethal to humans.

  18. α-Lipoic Acid Mitigates Arsenic-Induced Hematological Abnormalities in Adult Male Rats

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    Sonali Ghosh

    2017-05-01

    Full Text Available Background: Arsenic toxicity is a major global health problem and exposure via contaminated drinking water has been associated with hematological and other systemic disorders. The present investigation has been conducted in adult male rats to evaluate the protective ability of α-lipoic acid (ALA against such hematological disorders. Methods: Twenty-four adult male Wister rats (b.wt.130±10g were grouped and accordingly group I (control received the normal diet, group II (treated was given arsenic orally for 28 consecutive days as arsenic trioxide (3 mg/kgbw/rat/day whereas group III (supplemented received the same dose of arsenic along with ALA (25 mg/kgbw/rat/day as oral supplement. Hematological profile, plasma oxidant/antioxidant status, and erythrocyte morphology were assessed. Statistical analysis was done by one-way ANOVA using SPSS software (version 16.0. Results: Arsenic exposure caused reduction of erythrocyte (P=0.021, leucocyte (P<0.001, and hemoglobin (P=0.031 associated with echinocytic transformation as evidenced by light and scanning electron microscopic studies. The other significantly altered parameters include increased mean corpuscular volume (P=0.041 and lymphocytopenia (P<0.001 with insignificant neutropenia and eosinophilia. Altered serum oxidative balance as evidenced by decreased TAS (P<0.001 and increased TOS (P<0.001 with OSI (P<0.001 was also noted. The dietary supplementation of ALA has a beneficial effect against the observed (P<0.05 arsenic toxicities. It brings about the protection by restoring the hematological redox and inflammatory status near normal in treated rats. Arsenic-induced morphological alteration of erythrocytes was also partially attenuated by ALA supplementation. Conclusion: It is concluded that arsenicosis is associated with hematological alterations and ALA co-supplementation can partially alleviate these changes in an experimental male rat model.

  19. Importance of neural mechanisms in colonic mucosal and muscular dysfunction in adult rats following neonatal colonic irritation

    OpenAIRE

    Chaloner, A.; Rao, A.; Al-Chaer, E.D.; Meerveld, B. Greenwood-Van

    2009-01-01

    Previous studies have shown that early life trauma induced by maternal separation or colonic irritation leads to hypersensitivity to colorectal distension in adulthood. We tested the hypothesis that repetitive colorectal distension in neonates leads to abnormalities in colonic permeability and smooth muscle function in the adult rat. In neonatal rats, repetitive colorectal distension was performed on days 8, 10, and 12. As adults, stool consistency was graded from 0 (formed stool) to 3 (liqui...

  20. TRPC1 expression and distribution in rat hearts

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    W. Niu

    2009-12-01

    Full Text Available Transient receptor potential canonical (TRPC proteins have been identified as a family of plasma membrane calcium-permeable channels. TRPC proteins can be activated by various stimuli and act as cellular sensors in mammals. Stretch-activated ion channels (SACs have been proposed to underlie cardiac mechano-electric feedback (MEF, although the molecular entity of SAC remains unknown. There is evidence suggesting that transient receptor potential canonical 1 (TRPC1 is a stretch-activated ion channel. As a non-selective cation channel, TRPC1 may cause stretch-induced depolarization and arrhythmia and thus may contribute to the MEF of the heart. In this study, we examined the expression patterns of TRPC1 in detail at both the mRNA and protein levels in rat hearts.We isolated total RNA from the left and right atria, and the left and right ventricles, and detected TRPC1 mRNA in these tissues using reverse-transcriptase polymerase chain reaction (RT-PCR. To study the protein localization and targeting, we performed immunohistochemistry and immunofluorescence labeling with the antibody against TRPC1. TRPC1 was detected in the cardiomyocytes of the ventricle and atrium at both the mRNA and protein levels. The cell membrane and Ttubule showed strong fluorescence labeling in the ventricular myocytes. Purkinje cells, the endothelial cells and smooth muscle cells of the coronary arterioles also displayed TRPC1 labeling. No TRPC1 was detected in fibroblasts. In conclusion, TRPC1 is widely expressed in the rat heart, including in working cells, Purkinje cells and vascular cells, suggesting that it plays an important role in the heart. The specific distribution pattern offered a useful insight into its function in adult rat ventricular cells. Further investigations are needed to clarify the role of TRPC1 in regulating cardiac activity, including cardiac MEF.

  1. Estudo histomorfométrico dos cardiomiócitos do ventrículo esquerdo das ratas albinas durante a prenhez Histomorphometrical study of cardiomyocytes of the left ventricular of albino rats during pregnancy

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    A.W. Liberatori Filho

    1999-07-01

    Full Text Available OBJETIVO. No presente estudo propusemo-nos a avaliar, por meio da microscopia de luz, os aspectos morfológicos e morfométricos dos cardiomiócitos do ventrículo esquerdo de ratas albinas durante a prenhez. MÉTODOS. Acasalamos doze ratas virgens que foram dividas ao acaso em quatro grupos, de acordo com a idade gestacional. Os animais correspondentes a cada grupo foram sacrificados ao 1o(G-A, 7o(G-B, 14o(G-C e 21o(G-D dias de prenhez, sendo coletados fragmentos do terço médio do ventrículo esquerdo, os quais após processamento apropriado, permitiram observação adequada à microscopia de luz. A cariometria foi realizada mensurando-se os diâmetros maiores e menores dos cardiomiócitos com o auxílio de um tambor rotativo modelo K 8 X adaptado a um microscópio de luz. RESULTADOS. O estudo em nível da microscopia de luz praticamente não mostrou alterações com o decorrer da prenhez. No entanto, a morfometria revelou que os volumes dos cardiomiócitos estão aumentados no 14o dia da prenhez, mostrando-se estatisticamente significante quando comparado aos demais grupos estudados. Assim, nossos resultados demonstraram haver hipertrofia ventricular esquerda durante a gestação. CONCLUSÃO. Durante a gestação há um processo dinâmico reversível de remodelação ventricular em conseqüência das alterações adaptativas gravídicas.PURPOSE. In the present study we evaluated, by light microscopy, and throughout morphometry, whether hypertrophy of cardiac striated muscular fibers of left ventricular occur in albino rat, during pregnancy. METHODS. After maiting, 12 nuliparous rats were divided into four groups with three animals for each group. The female rats corresponding to each group were killed at 1st, 7th, 14th and 21st days of pregnancy. RESULTS. Observation, on light microscopy (H.E had at one view, did not display any alterations during pregnancy. However, the morphometry revealed that nuclei of cardiomyocytes are augmented in

  2. Effect of norbinaltorphimine on ∆⁹-tetrahydrocannabinol (THC)-induced taste avoidance in adolescent and adult Sprague-Dawley rats.

    Science.gov (United States)

    Flax, Shaun M; Wakeford, Alison G P; Cheng, Kejun; Rice, Kenner C; Riley, Anthony L

    2015-09-01

    The aversive effects of ∆(9)-tetrahydrocannabinol (THC) are mediated by activity at the kappa opioid receptor (KOR) as assessed in adult animals; however, no studies have assessed KOR involvement in the aversive effects of THC in adolescents. Given that adolescents have been reported to be insensitive to the aversive effects induced by KOR agonists, a different mechanism might mediate the aversive effects of THC in this age group. The present study was designed to assess the impact of KOR antagonism on the aversive effects of THC in adolescent and adult rats using the conditioned taste avoidance (CTA) procedure. Following a single pretreatment injection of norbinaltorphimine (norBNI; 15 mg/kg), CTAs induced by THC (0, 0.56, 1.0, 1.8, and 3.2 mg/kg) were assessed in adolescent (n = 84) and adult (n = 83) Sprague-Dawley rats. The KOR antagonist, norBNI, had weak and inconsistent effects on THC-induced taste avoidance in adolescent rats in that norBNI both attenuated and strengthened taste avoidance dependent on dose and trial. norBNI had limited impact on the final one-bottle avoidance and no effects on the two-bottle preference test. Interestingly, norBNI had no effect on THC-induced taste avoidance in adult rats as well. That norBNI had no significant effect on THC-induced avoidance in adults, and a minor and inconsistent effect in adolescents demonstrates that the aversive effects of THC are not mediated by KOR activity as assessed by the CTA design in Sprague-Dawley rats.

  3. Locomotor activity and catecholamine receptor binding in adult normotensive and spontaneously hypertensive rats

    International Nuclear Information System (INIS)

    Hellstrand, K.; Engel, J.

    1980-01-01

    The binding of 3 H-WB 4101, an α 1 -adrenoceptor antagonist, the membranes of the cerebral cortex, the hypothalamus, and the lower brainstem was examined in adult spontaneously hypertensive (SH) rats and in normotensive Wistar Kyoto (WK) controls. The specific binding of 3 H-WB 4101 (0.33 nM) was significantly higher in homogenates from the cerebral cortex of SH rats as compared to WK rats. No differences were detected between SH and WK rats in the specific binding of 3 H-spiroperidol (0.25 nM), a dopamine receptor antagonist, to membranes from the corpus striatum and the limbic forebrain. The locomotor activity was significantly higher in SH rats as compared to WK controls, in all probability due to a lack of habituation to environmental change. It is suggested that the high reactivity of SH rats is related to a disfunction in the noradrenergic neurons in the central nervous system. (author)

  4. The satiating hormone amylin enhances neurogenesis in the area postrema of adult rats

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    Claudia G. Liberini

    2016-10-01

    Full Text Available Objective: Adult neurogenesis in the subgranular zone and subventricular zone is generally accepted, but its existence in other brain areas is still controversial. Circumventricular organs, such as the area postrema (AP have recently been described as potential neurogenic niches in the adult brain. The AP is the major site of action of the satiating hormone amylin. Amylin has been shown to promote the formation of neuronal projections originating from the AP in neonatal rodents but the role of amylin in adult neurogenesis remains unknown. Methods: To test this, we first performed an RNA-sequencing of the AP of adult rats acutely injected with either amylin (20 μg/kg, amylin plus the amylin receptor antagonist AC187 (500 μg/kg or vehicle. Second, animals were subcutaneously equipped with minipumps releasing either amylin (50 μg/kg/day or vehicle for 3 weeks to assess cell proliferation and differentiation with the 5′-bromo-2-deoxyuridine (BrdU technique. Results: Acute amylin injections affected genes involved in pathways and processes that control adult neurogenesis. Amylin consistently upregulated NeuroD1 transcript and protein in the adult AP, and this effect was blocked by the co-administration of AC187. Further, chronic amylin treatment increased the number of newly proliferated AP-cells and significantly promoted their differentiation into neurons rather than astrocytes. Conclusion: Our findings revealed a novel role of the satiating hormone amylin in promoting neurogenesis in the AP of adult rats. Keywords: Amylin, Adult neurogenesis, Area postrema, BrdU, Circumventricular organs

  5. Left ventricular systolic function in sickle cell anaemia: an ...

    African Journals Online (AJOL)

    Keywords: Left ventricular systolic function, sickle cell anaemia, echocardiographic evaluation, adult Nigerian patients. ..... Quadratic .505. -0.390. 12.231. 8.587 .001*. Cubic .510. -0.180. 8.264. 8.619 .001*. This relationship was further evaluated by means of scat- ter plots and subsequently by regression analysis. The.

  6. Maternal-pup interaction disturbances induce long-lasting changes in the newborn rat pulmonary vasculature.

    Science.gov (United States)

    Shifrin, Yulia; Sadeghi, Sina; Pan, Jingyi; Jain, Amish; Fajardo, Andres F; McNamara, Patrick J; Belik, Jaques

    2015-11-15

    The factors accounting for the pathological maintenance of a high pulmonary vascular (PV) resistance postnatally remain elusive, but neonatal stressors may play a role in this process. Cross-fostering in the immediate neonatal period is associated with adult-onset vascular and behavioral changes, likely triggered by early-in-life stressors. In hypothesizing that fostering newborn rats induces long-lasting PV changes, we evaluated them at 14 days of age during adulthood and compared the findings with animals raised by their biological mothers. Fostering resulted in reduced maternal-pup contact time when compared with control newborns. At 2 wk of age, fostered rats exhibited reduced pulmonary arterial endothelium-dependent relaxation secondary to downregulation of tissue endothelial nitric oxide synthase expression and tetrahydrobiopterin deficiency-induced uncoupling. These changes were associated with neonatal onset-increased ANG II receptor type 1 expression, PV remodeling, and right ventricular hypertrophy that persisted into adulthood. The pulmonary arteries of adult-fostered rats exhibited a higher contraction dose response to ANG II and thromboxane A2, the latter of which was abrogated by the oxidant scavenger Tempol. In conclusion, fostering-induced neonatal stress induces long-standing PV changes modulated via the renin-angiotensin system. Copyright © 2015 the American Physiological Society.

  7. Low serum magnesium concentrations are associated with a high prevalence of premature ventricular complexes in obese adults with type 2 diabetes

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    Del Gobbo Liana C

    2012-03-01

    Full Text Available Abstract Background Premature ventricular complexes (PVC predict cardiovascular mortality among several adult populations. Increased arrhythmia prevalence has been reported during controlled magnesium (Mg depletion studies in adults. We thus hypothesized that serum magnesium (sMg concentrations are inversely associated with the prevalence of PVC in adults at high cardiovascular risk. Methods Anthropometric, demographic and lifestyle characteristics were assessed in 750 Cree adults, aged > 18 yrs, who participated in an age-stratified, cross-sectional health survey in Quebec, Canada. Holter electrocardiograms recorded heart rate variability and cardiac arrhythmias for two consecutive hours. Multivariate logistic regression was used to evaluate the associations between sMg and PVC. Results PVC prevalence in adults with hypomagnesemia (sMg ≤ 0.70 mmol/L was more than twice that of adults without hypomagnesemia (50% vs. 21%, p = 0.015; results were similar when adults with cardiovascular disease history were excluded. All hypomagnesemic adults with PVC had type 2 diabetes (T2DM. Prevalence of PVC declined across the sMg concentration gradient in adults with T2DM only (p 0.70 mmol/L was 0.24 (95% CI: 0.06-0.98 p = 0.046 compared to those with sMg ≤ 0.70 mmol/L. Conclusions sMg concentrations were inversely associated with the prevalence of PVC in patients with T2DM in a dose response manner, indicating that suboptimal sMg may be a contributor to arrhythmias among patients with T2DM.

  8. Impairment of male reproduction in adult rats exposed to hydroxyprogesterone caproate in utero

    Science.gov (United States)

    Pushpalatha, T.; Ramachandra Reddy, P.; Sreenivasula Reddy, P.

    Hydroxyprogesterone caproate is one of the most effective and widely used drugs for the treatment of uterine bleeding and threatened miscarriage in women. Hydroxyprogesterone caproate was administered to pregnant rats in order to assess the effect of intraperitoneal exposure to supranormal levels of hydroxyprogesterone caproate on the male reproductive potential in the first generation. The cauda epididymal sperm count and motility decreased significantly in rats exposed to hydroxyprogesterone caproate during embryonic development, when compared with control rats. The levels of serum testosterone decreased with an increase in follicle stimulating hormone and luteinizing hormone in adult rats exposed to hydroxyprogesterone caproate during the embryonic stage. It was suggested that the impairment of male reproductive performance could be mediated through the inhibition of testosterone production.

  9. Remote ischemic preconditioning differentially attenuates post-ischemic cardiac arrhythmia in streptozotocin-induced diabetic versus nondiabetic rats.

    Science.gov (United States)

    Hu, Zhaoyang; Chen, Mou; Zhang, Ping; Liu, Jin; Abbott, Geoffrey W

    2017-04-26

    Sudden cardiac death (SCD), a leading cause of global mortality, most commonly arises from a substrate of cardiac ischemia, but requires an additional trigger. Diabetes mellitus (DM) predisposes to SCD even after adjusting for other DM-linked cardiovascular pathology such as coronary artery disease. We previously showed that remote liver ischemia preconditioning (RLIPC) is highly protective against cardiac ischemia reperfusion injury (IRI) linked ventricular arrhythmias and myocardial infarction, via induction of the cardioprotective RISK pathway, and specifically, inhibitory phosphorylation of GSK-3β (Ser 9). We evaluated the impact of acute streptozotocin-induced DM on coronary artery ligation IRI-linked ventricular arrhythmogenesis and RLIPC therapy in rats. Post-IRI arrhythmia induction was similar in nondiabetic and DM rats, but, unexpectedly, DM rats exhibited lower incidence of SCD during reperfusion (41 vs. 100%), suggesting uncontrolled hyperglycemia does not acutely predispose to SCD. RLIPC was highly effective in both nondiabetic and DM rats at reducing incidence and duration of, and increasing latency to, all classes of ventricular tachyarrhythmias. In contrast, atrioventricular block (AVB) was highly responsive to RLIPC in nondiabetic rats (incidence reduced from 72 to 18%) but unresponsive in DM rats. RISK pathway induction was similar in nondiabetic and DM rats, thus not explaining the DM-specific resistance of AVB to therapy. Our findings uncover important acute DM-specific differences in responsiveness to remote preconditioning for ventricular tachyarrhythmias versus AVB, which may have clinical significance given that AVB is a malignant arrhythmia twofold more common in human diabetics than nondiabetics, and correlated to plasma glucose levels >10 mmol/L.

  10. Acquisition of i.v. cocaine self-administration in adolescent and adult male rats selectively bred for high and low saccharin intake.

    Science.gov (United States)

    Perry, Jennifer L; Anderson, Marissa M; Nelson, Sarah E; Carroll, Marilyn E

    2007-05-16

    Adolescence and excessive intake of saccharin have each been previously associated with enhanced vulnerability to drug abuse. In the present study, we focused on the relationship between these two factors using male adolescent and adult rats selectively bred for high (HiS) and low (LoS) levels of saccharin intake. On postnatal day 25 (adolescents) or 150 (adults), rats were implanted with an intravenous catheter and trained to self-administer cocaine (0.4 mg/kg) using an autoshaping procedure that consisted of two 6-h sessions. In the first 6 h, rats were given non-contingent cocaine infusions at random intervals 10 times per hour, and during the second 6-h session, rats were allowed to self-administer cocaine under a fixed ratio 1 (FR 1) lever-response contingency. Acquisition was defined as a total of at least 250 infusions over 5 consecutive days, and rats were given 30 days to meet the acquisition criterion. Subsequently, saccharin phenotype scores were determined by comparing 24-h saccharin and water consumption in two-bottle tests to verify HiS/LoS status. Adolescent LoS rats had a faster rate of acquisition of cocaine self-administration than adult LoS rats; however, adolescent and adult HiS rats acquired at the same rate. Both HiS and LoS adolescents had significantly higher saccharin phenotype scores than HiS and LoS adults, respectively. Additionally, saccharin score was negatively correlated with the number of days to meet the acquisition criterion for cocaine self-administration, but this was mostly accounted for by the HiS adolescents. These results suggest that during adolescence, compared with adulthood, rats have both an increased avidity for sweets and vulnerability to initiate drug abuse.

  11. Beneficial Effect of Ocimum sanctum (Linn) against Monocrotaline-Induced Pulmonary Hypertension in Rats.

    Science.gov (United States)

    Meghwani, Himanshu; Prabhakar, Pankaj; Mohammed, Soheb A; Dua, Pamila; Seth, Sandeep; Hote, Milind P; Banerjee, Sanjay K; Arava, Sudheer; Ray, Ruma; Maulik, Subir Kumar

    2018-04-17

    The study was designed to explore any beneficial effect of Ocimum sanctum (Linn) (OS) in experimental pulmonary hypertension (PH) in rats. OS is commonly known as “holy basil” and “Tulsi” and is used in the Indian System of Medicine as antidiabetic, antioxidant, hepatoprotective, adaptogenic, and cardioprotective. Monocrotaline (MCT) administration caused development of PH in rats after 28 days and rats were observed for 42 days. Treatments (sildenafil; 175 µg/kg, OS; 200 mg/kg) were started from day 29 after the development of PH and continued for 14 days. Parameters to assess the disease development and effectiveness of interventions were echocardiography, right and left ventricular systolic pressures, and right ventricular end diastolic pressure, percentage medial wall thickness (%MWT) of pulmonary artery, oxidative stress markers in lung tissue, NADPH oxidase (Nox-1) protein expression in lung, and mRNA expression of Bcl2 and Bax in right ventricular tissue. OS (200 mg/kg) treatment ameliorated increased lung weight to body weight ratio, right ventricular hypertrophy, increased RVSP, and RVoTD/AoD ratio. Moreover, OS treatment decreases Nox-1 expression and increases expression of Bcl2/Bax ratio caused by MCT. The present study demonstrates that OS has therapeutic ability against MCT-induced PH in rat which are attributed to its antioxidant effect. The effect of OS was comparable with sildenafil.

  12. A large ventricular septal defect complicating resuscitation after blunt trauma

    Directory of Open Access Journals (Sweden)

    Henry D I De′Ath

    2012-01-01

    Full Text Available A young adult pedestrian was admitted to hospital after being hit by a car. On arrival to the Accident and Emergency Department, the patient was tachycardic, hypotensive, hypoxic, and acidotic with a Glasgow Coma Scale of 3. Despite initial interventions, the patient remained persistently hypotensive. An echocardiogram demonstrated a traumatic ventricular septal defect (VSD with right ventricular strain and increased pulmonary artery pressure. Following a period of stabilization, open cardiothoracic surgery was performed and revealed an aneurysmal septum with a single large defect. This was repaired with a bovine patch, resulting in normalization of right ventricular function. This case provides a vivid depiction of a large VSD in a patient following blunt chest trauma with hemodynamic compromise. In all thoracic trauma patients, and particularly those poorly responsive to resuscitation, VSDs should be considered. Relevant investigations and management strategies are discussed.

  13. Repeated exposure to methamphetamine induces sex-dependent hypersensitivity to ischemic injury in the adult rat heart.

    Directory of Open Access Journals (Sweden)

    Boyd R Rorabaugh

    Full Text Available We previously reported that adult female, but not male rats that were prenatally exposed to methamphetamine exhibit myocardial hypersensitivity to ischemic injury. However, it is unknown whether hypersensitivity to ischemic injury develops when rats are exposed to methamphetamine during adulthood. The goal of this study was to determine whether methamphetamine exposure during adulthood sensitizes the heart to ischemic injury.Adult male and female rats received daily injections of methamphetamine (5 mg/kg or saline for 10 days. Their hearts were isolated on day 11 and subjected to a 20 min ischemic insult on a Langendorff isolated heart apparatus. Cardiac contractile function was measured by an intraventricular balloon, and infarct size was measured by triphenyltetrazolium chloride staining.Hearts from methamphetamine-treated females exhibited significantly larger infarcts and suppressed postischemic recovery of contractile function compared to hearts from saline-treated females. In contrast, methamphetamine had no effect on infarct size or contractile recovery in male hearts. Subsequent experiments demonstrated that hypersensitivity to ischemic injury persisted in female hearts following a 1 month period of abstinence from methamphetamine. Myocardial protein kinase C-ε expression, Akt phosphorylation, and ERK phosphorylation were unaffected by adult exposure to methamphetamine.Exposure of adult rats to methamphetamine sex-dependently increases the extent of myocardial injury following an ischemic insult. These data suggest that women who have a heart attack might be at risk of more extensive myocardial injury if they have a recent history of methamphetamine abuse.

  14. Repeated exposure to methamphetamine induces sex-dependent hypersensitivity to ischemic injury in the adult rat heart

    Science.gov (United States)

    Seeley, Sarah L.; Stoops, Thorne S.; D’Souza, Manoranjan S.

    2017-01-01

    Background We previously reported that adult female, but not male rats that were prenatally exposed to methamphetamine exhibit myocardial hypersensitivity to ischemic injury. However, it is unknown whether hypersensitivity to ischemic injury develops when rats are exposed to methamphetamine during adulthood. The goal of this study was to determine whether methamphetamine exposure during adulthood sensitizes the heart to ischemic injury. Methods Adult male and female rats received daily injections of methamphetamine (5 mg/kg) or saline for 10 days. Their hearts were isolated on day 11 and subjected to a 20 min ischemic insult on a Langendorff isolated heart apparatus. Cardiac contractile function was measured by an intraventricular balloon, and infarct size was measured by triphenyltetrazolium chloride staining. Results Hearts from methamphetamine-treated females exhibited significantly larger infarcts and suppressed postischemic recovery of contractile function compared to hearts from saline-treated females. In contrast, methamphetamine had no effect on infarct size or contractile recovery in male hearts. Subsequent experiments demonstrated that hypersensitivity to ischemic injury persisted in female hearts following a 1 month period of abstinence from methamphetamine. Myocardial protein kinase C-ε expression, Akt phosphorylation, and ERK phosphorylation were unaffected by adult exposure to methamphetamine. Conclusions Exposure of adult rats to methamphetamine sex-dependently increases the extent of myocardial injury following an ischemic insult. These data suggest that women who have a heart attack might be at risk of more extensive myocardial injury if they have a recent history of methamphetamine abuse. PMID:28575091

  15. Associations of Blood Pressure Dipping Patterns With Left Ventricular Mass and Left Ventricular Hypertrophy in Blacks: The Jackson Heart Study.

    Science.gov (United States)

    Abdalla, Marwah; Caughey, Melissa C; Tanner, Rikki M; Booth, John N; Diaz, Keith M; Anstey, D Edmund; Sims, Mario; Ravenell, Joseph; Muntner, Paul; Viera, Anthony J; Shimbo, Daichi

    2017-04-05

    Abnormal diurnal blood pressure (BP), including nondipping patterns, assessed using ambulatory BP monitoring, have been associated with increased cardiovascular risk among white and Asian adults. We examined the associations of BP dipping patterns (dipping, nondipping, and reverse dipping) with cardiovascular target organ damage (left ventricular mass index and left ventricular hypertrophy), among participants from the Jackson Heart Study, an exclusively black population-based cohort. Analyses included 1015 participants who completed ambulatory BP monitoring and had echocardiography data from the baseline visit. Participants were categorized based on the nighttime to daytime systolic BP ratio into 3 patterns: dipping pattern (≤0.90), nondipping pattern (>0.90 to ≤1.00), and reverse dipping pattern (>1.00). The prevalence of dipping, nondipping, and reverse dipping patterns was 33.6%, 48.2%, and 18.2%, respectively. In a fully adjusted model, which included antihypertensive medication use and clinic and daytime systolic BP, the mean differences in left ventricular mass index between reverse dipping pattern versus dipping pattern was 8.3±2.1 g/m 2 ( P pattern versus dipping pattern was -1.0±1.6 g/m 2 ( P =0.536). Compared with participants with a dipping pattern, the prevalence ratio for having left ventricular hypertrophy was 1.65 (95% CI, 1.05-2.58) and 0.96 (95% CI, 0.63-1.97) for those with a reverse dipping pattern and nondipping pattern, respectively. In this population-based study of blacks, a reverse dipping pattern was associated with increased left ventricular mass index and a higher prevalence of left ventricular hypertrophy. Identification of a reverse dipping pattern on ambulatory BP monitoring may help identify black at increased risk for cardiovascular target organ damage. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  16. Aversive effects of ethanol in adolescent versus adult rats: potential causes and implication for future drinking.

    Science.gov (United States)

    Schramm-Sapyta, Nicole L; DiFeliceantonio, Alexandra G; Foscue, Ethan; Glowacz, Susan; Haseeb, Naadeyah; Wang, Nancy; Zhou, Cathy; Kuhn, Cynthia M

    2010-12-01

    Many people experiment with alcohol and other drugs of abuse during their teenage years. Epidemiological evidence suggests that younger initiates into drug taking are more likely to develop problematic drug seeking behavior, including binge and other high-intake behaviors. The level of drug intake for any individual depends on the balance of rewarding and aversive effects of the drug in that individual. Multiple rodent studies have demonstrated that aversive effects of drugs of abuse are reduced in adolescent compared to adult animals. In this study, we addressed 2 key questions: First, do reduced aversive effects of ethanol in younger rats correlate with increased ethanol consumption? Second, are the reduced aversive effects in adolescents attributable to reduced sensitivity to ethanol's physiologic effects? Adolescent and adult rats were tested for ethanol conditioned taste aversion (CTA) followed by a voluntary drinking period, including postdeprivation consumption. Multivariate regression was used to assess correlations. In separate experiments, adolescent and adult rats were tested for their sensitivity to the hypothermic and sedative effects of ethanol, and for blood ethanol concentrations (BECs). We observed that in adolescent rats but not adults, taste aversion was inversely correlated with postdeprivation consumption. Adolescents also exhibited a greater increase in consumption after deprivation than adults. Furthermore, the age difference in ethanol CTA was not attributable to differences in hypothermia, sedation, or BECs. These results suggest that during adolescence, individuals that are insensitive to aversive effects are most likely to develop problem drinking behaviors. These results underscore the importance of the interaction between developmental stage and individual variation in sensitivity to alcohol. Copyright © 2010 by the Research Society on Alcoholism.

  17. Negative Effect of Zinc on Testes, Testosterone and Gonadotrophins Levels in Adult Male Wistar Rats

    Directory of Open Access Journals (Sweden)

    D. Sohrabi

    2008-10-01

    Full Text Available Background and ObjectivesThe toxic effects of zinc leading to sebaceous gland closure, skin eczema and blister have been previously demonstrated in other studies. The aim of this study is to determine the chronic effects of zinc chloride (ZnCl2 on testicular tissues, testosterone and gonadotrophins in adult male Wistar rats.Methods Twenty four Adult male Wistar rats were divided in to two groups of study and control with each group consisting of 12 rats. Study group rats received 10 mg/kg interaperitoneal Zinc chloride in normal saline (N.S every other day for 30 days. Control group rats received N.S during this time. Blood sample for hormonal evaluation were collected from hearts of these rats. The rats were destroyed and their testes were removed and fixed in a 10% formaldehyde and glutaraldehyde solution.ResultsThe results of this study showed a significant decrease in the level of LH and testosterone hormone among the rats in the study group compared to the control group with p< 0.001 and p< 0.01 respectively. Study of fine structure of testicular cells and tissues in the study group rats revealed swelling of mitochondria, increase in smooth endoplasmic reticulum vacuolization and lysosomic granules (Autophagic vacuoles in cytosol of their germinal cells.ConclusionBased on the results of this study consumption of large amount of compounds which contain zinc should be controlled and limited among men. There is a need for further studies to evaluate and determine the reversibility of most hormonal and physiological changes due to usage of zinc containing compounds.Keywords: Zinc Chloride; Testis; Testosterone; Gonadotrophins

  18. Angiotensin II prevents hypoxic pulmonary hypertension and vascular changes in rat

    International Nuclear Information System (INIS)

    Rabinovitch, M.; Mullen, M.; Rosenberg, H.C.; Maruyama, K.; O'Brodovich, H.; Olley, P.M.

    1988-01-01

    Angiotensin II, a vasoconstrictor, has been previously demonstrated to produce a secondary vasodilatation due to release of prostaglandins. Because of this effect, the authors investigated whether infusion of exogenous angiotensin II via miniosmopumps in rats during a 1-wk exposure to chronic hypobaric hypoxia might prevent pulmonary hypertension, right ventricular hypertrophy, and vascular changes. They instrumented the rats with indwelling cardiovascular catheters and compared the hemodynamic and structural response in animals given angiotensin II, indomethacin in addition to angiotensin II (to block prostaglandin production), or saline with or without indomethacin. They then determine whether angiotensin II infusion also prevents acute hypoxic pulmonary vasoconstriction. They observed that exogenous angiotensin II infusion abolished the rise in pulmonary artery pressure, the right ventricular hypertrophy, and the vascular changes induced during chronic hypoxia in control saline-infused rats with or without indomethacin. The protective effects of angiotensin II was lost when indomethacin was given to block prostaglandin synthesis. During acute hypoxia, both antiotensin II and prostacyclin infusion similarly prevented the rise in pulmonary artery pressure observed in saline-infused rats and in rats given indomethacin or saralasin in addition to angiotensin II. Thus exogenous angiotensin II infusion prevents chronic hypoxic pulmonary hypertension, associated right ventricular hypertrophy, and vascular changes and blocks acute hypoxic pulmonary hypertension, and this is likely related to its ability to release vasodilator prostaglandins

  19. Systolic left ventricular function according to left ventricular concentricity and dilatation in hypertensive patients

    DEFF Research Database (Denmark)

    Bang, Casper; Gerdts, Eva; Aurigemma, Gerard P

    2013-01-01

    Left ventricular hypertrophy [LVH, high left ventricular mass (LVM)] is traditionally classified as concentric or eccentric based on left ventricular relative wall thickness. We evaluated left ventricular systolic function in a new four-group LVH classification based on left ventricular dilatation...... [high left ventricular end-diastolic volume (EDV) index and concentricity (LVM/EDV)] in hypertensive patients....

  20. Left ventricular function in patients with ventricular arrhythmias and aortic valve disease

    International Nuclear Information System (INIS)

    Santinga, J.T.; Kirsh, M.M.; Brady, T.J.; Thrall, J.; Pitt, B.

    1983-01-01

    Forty patients having aortic valve replacement were evaluated preoperatively for ventricular arrhythmia and left ventricular ejection fraction. Arrhythmias were classified as complex or simple using the Lown criteria on the 24-hour ambulatory electrocardiogram; ejection fractions were determined by radionuclide gated blood pool analysis and contrast angiography. The ejection fractions determined by radionuclide angiography were 59.1 +/- 13.1% for 26 patients with simple or no ventricular arrhythmias, and 43.9 +/- 20.3% for 14 patients with complex ventricular arrhythmias (p less than 0.01). Ejection fractions determined by angiography, available for 31 patients, were also lower in patients with complex ventricular arrhythmias (61.1 +/- 16.3% versus 51.4 +/- 13.4%; p less than 0.05). Seven of 9 patients showing conduction abnormalities on the electrocardiogram had complex ventricular arrhythmias. Eight of 20 patients with aortic stenosis had complex ventricular arrhythmias, while 2 of 13 patients with aortic insufficiency had such arrhythmias. It is concluded that decreased left ventricular ejection fraction, intraventricular conduction abnormalities, and aortic stenosis are associated with an increased frequency of complex ventricular arrhythmias in patients with aortic valve disease

  1. Effects of physical exercise on object recognition memory in adult rats of postnatal isoflurane exposures

    Directory of Open Access Journals (Sweden)

    Xiao-yan FANG

    2017-08-01

    Full Text Available Objective To investigate effects of physical exercise (PE on object recognition memory in adult rats of postnatal isoflurane (Iso exposures. Methods One hundred and ten postnatal 7-day SD rats (P7 were randomly divided into four groups: normal control group (Naive, Naive+PE group (received physical exercise in P21: a treadmill exercise 30min each day, 5 times/week, for 6 weeks, Iso group (three times of 2-hour Iso exposure in P7, P9, and P11, and Iso+PE group (received PE in P21 after postnatal Iso exposures. In P67, behavioral testing was conducted including open field and object recognition task (ORT, recording the time (Discrimination Ratios, DR that rats spent on exploring each object, evaluating effects of PE on object recognition memory. Results There was no significant difference in influence of PE on open field testing in all of the groups (P>0.05. Compared with Naive, there was no group difference in DR (P>0.05 for all groups, but the DR of Iso male rats was significantly higher than that of Naive female rats in P67, with significant difference (P=0.034. Compared with non-PE groups, whether or not postnatal Iso exposures, the DR of PE male groups was significantly higher (compared with Naive and Iso group: P67, P=0.050, P=0.017; P95, P=0.037, P=0.019; in female rats, the DR for ISO+PE group was lower than that of Iso group in P67 (P=0.036, but the DR of Naive+PE group was higher than that of Naive group in P95 (P=0.004. Compared with male rats, the DR of non-PE female rats was significantly higher in P67 (vis. Naive and Iso group: P=0.022, P=0.011; but in P95, the DR of non- Iso female groups was significantly higher than that of male groups (vis. Naive and Naive+PE: P=0.008, P=0.017. Conclusions There is no obvious impact of postnatal Iso exposures on object recognition memory of adult rats. These results also indicate that postnatal PE could improve object recognition memory of non-spatial learning in adult rats. In addition, exercise

  2. Do right-ventricular trabeculae gain energetic advantage from having a greater velocity of shortening?

    Science.gov (United States)

    Pham, Toan; Han, June-Chiew; Taberner, Andrew; Loiselle, Denis

    2017-10-15

    We designed a study to test whether velocity of shortening in right-ventricular tissue preparations is greater than that of the left side under conditions mimicking those encountered by the heart in vivo. Our experiments allowed us to explore whether greater velocity of shortening results in any energetic advantage. We found that velocity of shortening was higher in the rat right-ventricular trabeculae. These results at the tissue level seem paradoxical to the velocity of ventricular ejection at the organ level, and are not always in accord with shortening of unloaded cells. Despite greater velocity of shortening in right-ventricular trabeculae, they neither gained nor lost advantage with respect to both mechanical efficiency and the heat generated during shortening. Our study aimed to ascertain whether the interventricular difference of shortening velocity, reported for isolated cardiac tissues in vitro, affects interventricular mechano-energetic performance when tested under physiological conditions using a shortening protocol designed to mimic those in vivo. We isolated trabeculae from both ventricles of the rat, mounted them in a calorimeter, and performed experiments at 37°C and 5 Hz stimulus frequency to emulate conditions of the rat heart in vivo. Each trabecula was subjected to two experimental protocols: (i) isotonic work-loop contractions at a variety of afterloads, and (ii) isometric contractions at a variety of preloads. Velocity of shortening was calculated from the former protocol during the isotonic shortening phase of the contraction. Simultaneous measurements of force-length work and heat output allowed calculation of mechanical efficiency. The shortening-dependent thermal component was quantified from the difference in heat output between the two protocols. Our results show that both extent of shortening and velocity of shortening were higher in trabeculae from the right ventricle. Despite these differences, trabeculae from both ventricles

  3. Calorie restriction attenuates cardiac remodeling and diastolic dysfunction in a rat model of metabolic syndrome.

    Science.gov (United States)

    Takatsu, Miwa; Nakashima, Chieko; Takahashi, Keiji; Murase, Tamayo; Hattori, Takuya; Ito, Hiromi; Murohara, Toyoaki; Nagata, Kohzo

    2013-11-01

    Calorie restriction (CR) can modulate the features of obesity-related metabolic and cardiovascular diseases. We have recently characterized DahlS.Z-Lepr(fa)/Lepr(fa) (DS/obese) rats, derived from a cross between Dahl salt-sensitive and Zucker rats, as a new animal model of metabolic syndrome. DS/obese rats develop hypertension and manifest left ventricular remodeling and diastolic dysfunction, as well as increased cardiac oxidative stress and inflammation. We have now investigated the effects of CR on cardiac pathophysiology in DS/obese rats. DS/obese rats were fed either normal laboratory chow ad libitum or a calorie-restricted diet (65% of the average food intake for ad libitum) from 9 to 13 weeks. Age-matched homozygous lean (DahlS.Z-Lepr(+)/Lepr(+) or DS/lean) littermates served as controls. CR reduced body weight in both DS/obese and DS/lean rats, as well as attenuated the development of hypertension in DS/obese rats without affecting blood pressure in DS/lean rats. CR also reduced body fat content, ameliorated left ventricular hypertrophy, fibrosis, and diastolic dysfunction, and attenuated cardiac oxidative stress and inflammation in DS/obese rats. In addition, it increased serum adiponectin concentration, as well as downregulated the expression of angiotensin-converting enzyme and angiotensin II type 1A receptor genes in the heart of DS/obese rats. Our results thus show that CR attenuated obesity and hypertension, as well as left ventricular remodeling and diastolic dysfunction in DS/obese rats, with these latter effects being associated with reduced cardiac oxidative stress and inflammation.

  4. Compartmentalized cAMP Signaling Associated With Lipid Raft and Non-raft Membrane Domains in Adult Ventricular Myocytes.

    Science.gov (United States)

    Agarwal, Shailesh R; Gratwohl, Jackson; Cozad, Mia; Yang, Pei-Chi; Clancy, Colleen E; Harvey, Robert D

    2018-01-01

    Aim: Confining cAMP production to discrete subcellular locations makes it possible for this ubiquitous second messenger to elicit unique functional responses. Yet, factors that determine how and where the production of this diffusible signaling molecule occurs are incompletely understood. The fluid mosaic model originally proposed that signal transduction occurs through random interactions between proteins diffusing freely throughout the plasma membrane. However, it is now known that the movement of membrane proteins is restricted, suggesting that the plasma membrane is segregated into distinct microdomains where different signaling proteins can be concentrated. In this study, we examined what role lipid raft and non-raft membrane domains play in compartmentation of cAMP signaling in adult ventricular myocytes. Methods and Results: The freely diffusible fluorescence resonance energy transfer-based biosensor Epac2-camps was used to measure global cytosolic cAMP responses, while versions of the probe targeted to lipid raft (Epac2-MyrPalm) and non-raft (Epac2-CAAX) domains were used to monitor local cAMP production near the plasma membrane. We found that β-adrenergic receptors, which are expressed in lipid raft and non-raft domains, produce cAMP responses near the plasma membrane that are distinctly different from those produced by E-type prostaglandin receptors, which are expressed exclusively in non-raft domains. We also found that there are differences in basal cAMP levels associated with lipid raft and non-raft domains, and that this can be explained by differences in basal adenylyl cyclase activity associated with each of these membrane environments. In addition, we found evidence that phosphodiesterases 2, 3, and 4 work together in regulating cAMP activity associated with both lipid raft and non-raft domains, while phosphodiesterase 3 plays a more prominent role in the bulk cytoplasmic compartment. Conclusion: These results suggest that different membrane

  5. Autonomic responses during acute myocardial infarction in the rat model: implications for arrhythmogenesis.

    Science.gov (United States)

    Kolettis, Theofilos M; Kontonika, Marianthi; Lekkas, Panagiotis; Vlahos, Antonios P; Baltogiannis, Giannis G; Gatzoulis, Konstantinos A; Chrousos, George P

    2018-04-10

    Autonomic responses participate in the pathophysiology of acute myocardial infarction, but their precise time course remains unclear. Here, we investigated the autonomic activity and ventricular tachyarrhythmias in conscious, unrestrained rats post-infarction. The left coronary artery was ligated in 12 Wistar rats, and six rats were sham operated, followed by 24-h electrocardiographic recording via implanted telemetry transmitters. Sympathetic activity was assessed by detrended fluctuation analysis and vagal activity by time- and frequency-domain analysis of heart rate variability. The duration of the ventricular tachyarrhythmias was measured, and voluntary motion served as a marker of heart failure. In sham-operated rats, heart rate and sympathetic activity remained low, whereas vagal activity rose progressively after the fourth hour. Post-ligation, medium-sized antero-septal necrosis was observed, reaching ~20% of the left ventricular volume; tachyarrhythmias were frequent, displaying a bimodal curve, and motion counts were low. Vagal activity decreased early post-ligation, coinciding with a high incidence of tachyarrhythmias, but tended to rise subsequently in rats with higher motion counts. Sympathetic activity increased after the third hour, along with a second tachyarrhythmia peak, and remained elevated throughout the 24-h period. Vagal withdrawal, followed by gradual sympathetic activation, may participate in arrhythmogenesis during acute myocardial infarction.

  6. Stochastic Simulation of Cardiac Ventricular Myocyte Calcium Dynamics and Waves

    OpenAIRE

    Tuan, Hoang-Trong Minh; Williams, George S. B.; Chikando, Aristide C.; Sobie, Eric A.; Lederer, W. Jonathan; Jafri, M. Saleet

    2011-01-01

    A three dimensional model of calcium dynamics in the rat ventricular myocyte was developed to study the mechanism of calcium homeostasis and pathological calcium dynamics during calcium overload. The model contains 20,000 calcium release units (CRUs) each containing 49 ryanodine receptors. The model simulates calcium sparks with a realistic spontaneous calcium spark rate. It suggests that in addition to the calcium spark-based leak, there is an invisible calcium leak caused by the stochastic ...

  7. Ursodeoxycholic acid prevents ventricular conduction slowing and arrhythmia by restoring T-type calcium current in fetuses during cholestasis

    Science.gov (United States)

    Adeyemi, Oladipupo; Alvarez-Laviada, Anita; Schultz, Francisca; Ibrahim, Effendi; Trauner, Michael; Williamson, Catherine; Glukhov, Alexey V.

    2017-01-01

    Background Increased maternal serum bile acid concentrations in intrahepatic cholestasis of pregnancy (ICP) are associated with fetal cardiac arrhythmias. Ursodeoxycholic acid (UDCA) has been shown to demonstrate anti-arrhythmic properties via preventing ICP-associated cardiac conduction slowing and development of reentrant arrhythmias, although the cellular mechanism is still being elucidated. Methods High-resolution fluorescent optical mapping of electrical activity and electrocardiogram measurements were used to characterize effects of UDCA on one-day-old neonatal and adult female Langendorff-perfused rat hearts. ICP was modelled by perfusion of taurocholic acid (TC, 400μM). Whole-cell calcium currents were recorded from neonatal rat and human fetal cardiomyocytes. Results TC significantly prolonged the PR interval by 11.0±3.5% (P<0.05) and slowed ventricular conduction velocity (CV) by 38.9±5.1% (P<0.05) exclusively in neonatal and not in maternal hearts. A similar CV decline was observed with the selective T-type calcium current (ICa,T) blocker mibefradil 1μM (23.0±6.2%, P<0.05), but not with the L-type calcium current (ICa,L) blocker nifedipine 1μM (6.9±6.6%, NS). The sodium channel blocker lidocaine (30μM) reduced CV by 60.4±4.5% (P<0.05). UDCA co-treatment was protective against CV slowing induced by TC and mibefradil, but not against lidocaine. UDCA prevented the TC-induced reduction in the ICa,T density in both isolated human fetal (−10.2±1.5 versus −5.5±0.9 pA/pF, P<0.05) and neonatal rat ventricular myocytes (−22.3±1.1 versus −9.6±0.8 pA/pF, P<0.0001), whereas UDCA had limited efficacy on the ICa,L. Conclusion Our findings demonstrate that ICa,T plays a significant role in ICP-associated fetal cardiac conduction slowing and arrhythmogenesis, and is an important component of the fetus-specific anti-arrhythmic activity of UDCA. PMID:28934223

  8. Ursodeoxycholic acid prevents ventricular conduction slowing and arrhythmia by restoring T-type calcium current in fetuses during cholestasis.

    Directory of Open Access Journals (Sweden)

    Oladipupo Adeyemi

    Full Text Available Increased maternal serum bile acid concentrations in intrahepatic cholestasis of pregnancy (ICP are associated with fetal cardiac arrhythmias. Ursodeoxycholic acid (UDCA has been shown to demonstrate anti-arrhythmic properties via preventing ICP-associated cardiac conduction slowing and development of reentrant arrhythmias, although the cellular mechanism is still being elucidated.High-resolution fluorescent optical mapping of electrical activity and electrocardiogram measurements were used to characterize effects of UDCA on one-day-old neonatal and adult female Langendorff-perfused rat hearts. ICP was modelled by perfusion of taurocholic acid (TC, 400μM. Whole-cell calcium currents were recorded from neonatal rat and human fetal cardiomyocytes.TC significantly prolonged the PR interval by 11.0±3.5% (P<0.05 and slowed ventricular conduction velocity (CV by 38.9±5.1% (P<0.05 exclusively in neonatal and not in maternal hearts. A similar CV decline was observed with the selective T-type calcium current (ICa,T blocker mibefradil 1μM (23.0±6.2%, P<0.05, but not with the L-type calcium current (ICa,L blocker nifedipine 1μM (6.9±6.6%, NS. The sodium channel blocker lidocaine (30μM reduced CV by 60.4±4.5% (P<0.05. UDCA co-treatment was protective against CV slowing induced by TC and mibefradil, but not against lidocaine. UDCA prevented the TC-induced reduction in the ICa,T density in both isolated human fetal (-10.2±1.5 versus -5.5±0.9 pA/pF, P<0.05 and neonatal rat ventricular myocytes (-22.3±1.1 versus -9.6±0.8 pA/pF, P<0.0001, whereas UDCA had limited efficacy on the ICa,L.Our findings demonstrate that ICa,T plays a significant role in ICP-associated fetal cardiac conduction slowing and arrhythmogenesis, and is an important component of the fetus-specific anti-arrhythmic activity of UDCA.

  9. Arrhythmogenic Right Ventricular Cardiomyopathy in an Endurance Athlete Presenting with Ventricular Tachycardia and Normal Right Ventricular Function.

    Science.gov (United States)

    Hedley, Jeffrey S; Al Mheid, Ibhar; Alikhani, Zoubin; Pernetz, Maria A; Kim, Jonathan H

    2017-08-01

    Arrhythmogenic right ventricular cardiomyopathy, a genetically inherited disease that results in fibrofatty replacement of normal cardiac myocytes, has been associated with sudden cardiac death in athletes. Long-term participation in endurance exercise hastens the development of both the arrhythmic and structural arrhythmogenic right ventricular cardiomyopathy phenotypes. We describe the unusual case of a 34-year-old, symptomatic, female endurance athlete who had arrhythmogenic right ventricular cardiomyopathy in the presence of a structurally normal right ventricle. Clinicians should be aware of this infrequent presentation when evaluating athletic patients who have ventricular arrhythmias and normal findings on cardiac imaging studies.

  10. Prophylactic implantable defibrillator in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia and no prior ventricular fibrillation or sustained ventricular tachycardia.

    LENUS (Irish Health Repository)

    Corrado, Domenico

    2010-09-21

    The role of implantable cardioverter-defibrillator (ICD) in patients with arrhythmogenic right ventricular cardiomyopathy\\/dysplasia and no prior ventricular fibrillation (VF) or sustained ventricular tachycardia is an unsolved issue.

  11. Prenatal zinc reduces stress response in adult rat offspring exposed to lipopolysaccharide during gestation.

    Science.gov (United States)

    Galvão, Marcella C; Chaves-Kirsten, Gabriela P; Queiroz-Hazarbassanov, Nicolle; Carvalho, Virgínia M; Bernardi, Maria M; Kirsten, Thiago B

    2015-01-01

    Previous investigations by our group have shown that prenatal treatment with lipopolysaccharide (LPS; 100 μg/kg, intraperitoneally) on gestation day (GD) 9.5 in rats, which mimics infections by Gram-negative bacteria, induces short- and long-term behavioral and neuroimmune changes in the offspring. Because LPS induces hypozincemia, dams were treated with zinc after LPS in an attempt to prevent or ameliorate the impairments induced by prenatal LPS exposure. LPS can also interfere with hypothalamic-pituitary-adrenal (HPA) axis development; thus, behavioral and neuroendocrine parameters linked to HPA axis were evaluated in adult offspring after a restraint stress session. We prenatally exposed Wistar rats to LPS (100 μg/kg, intraperitoneally, on GD 9.5). One hour later they received zinc (ZnSO4, 2 mg/kg, subcutaneously). Adult female offspring that were in metestrus/diestrus were submitted to a 2 h restraint stress session. Immediately after the stressor, 22 kHz ultrasonic vocalizations, open field behavior, serum corticosterone and brain-derived neurotrophic factor (BDNF) levels, and striatal and hypothalamic neurotransmitter and metabolite levels were assessed. Offspring that received prenatal zinc after LPS presented longer periods in silence, increased locomotion, and reduced serum corticosterone and striatal norepinephrine turnover compared with rats treated with LPS and saline. Prenatal zinc reduced acute restraint stress response in adult rats prenatally exposed to LPS. Our findings suggest a potential beneficial effect of prenatal zinc, in which the stress response was reduced in offspring that were stricken with infectious/inflammatory processes during gestation. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Severity of structural and functional right ventricular remodeling depends on training load in an experimental model of endurance exercise.

    Science.gov (United States)

    Sanz-de la Garza, Maria; Rubies, Cira; Batlle, Montserrat; Bijnens, Bart H; Mont, Lluis; Sitges, Marta; Guasch, Eduard

    2017-09-01

    Arrhythmogenic right ventricular (RV) remodeling has been reported in response to regular training, but it remains unclear how exercise intensity affects the presence and extent of such remodeling. We aimed to assess the relationship between RV remodeling and exercise load in a long-term endurance training model. Wistar rats were conditioned to run at moderate (MOD; 45 min, 30 cm/s) or intense (INT; 60 min, 60 cm/s) workloads for 16 wk; sedentary rats served as controls. Cardiac remodeling was assessed with standard echocardiographic and tissue Doppler techniques, sensor-tip pressure catheters, and pressure-volume loop analyses. After MOD training, both ventricles similarly dilated (~16%); the RV apical segment deformation, but not the basal segment deformation, was increased [apical strain rate (SR): -2.9 ± 0.5 vs. -3.3 ± 0.6 s -1 , SED vs. MOD]. INT training prompted marked RV dilatation (~26%) but did not further dilate the left ventricle (LV). A reduction in both RV segments' deformation in INT rats (apical SR: -3.3 ± 0.6 vs. -3.0 ± 0.4 s -1 and basal SR: -3.3 ± 0.7 vs. -2.7 ± 0.6 s -1 , MOD vs. INT) led to decreased global contractile function (maximal rate of rise of LV pressure: 2.53 ± 0.15 vs. 2.17 ± 0.116 mmHg/ms, MOD vs. INT). Echocardiography and hemodynamics consistently pointed to impaired RV diastolic function in INT rats. LV systolic and diastolic functions remained unchanged in all groups. In conclusion, we showed a biphasic, unbalanced RV remodeling response with increasing doses of exercise: physiological adaptation after MOD training turns adverse with INT training, involving disproportionate RV dilatation, decreased contractility, and impaired diastolic function. Our findings support the existence of an exercise load threshold beyond which cardiac remodeling becomes maladaptive. NEW & NOTEWORTHY Exercise promotes left ventricular eccentric hypertrophy with no changes in systolic or diastolic function in healthy rats. Conversely, right

  13. Chronic intermittent hypoxia promotes expression of 3-mercaptopyruvate sulfurtransferase in adult rat medulla oblongata.

    Science.gov (United States)

    Li, Mingqiang; Nie, Lihong; Hu, Yajie; Yan, Xiang; Xue, Lian; Chen, Li; Zhou, Hua; Zheng, Yu

    2013-12-01

    The present experiments were carried out to investigate the expression of 3-mercaptopyruvate sulfurtransferase (3MST) in medulla oblongata of rats and effects of chronic intermittent hypoxia (CIH) on its expression. Sprague Dawley adult rats were randomly divided into two groups, including control (Con) group and CIH group. The endogenous production of hydrogen sulfide (H2S) in medulla oblongata tissue homogenates was measured using the methylene blue assay method, 3MST mRNA and protein expression were analyzed by RT-PCR and Western blotting, respectively, and the expression of 3MST in the neurons of respiratory-related nuclei in medulla oblongata of rats was investigated with immunohistochemical technique. CIH elevated the endogenous H2S production in rat medulla oblongata (Pmedulla oblongata of rats and CIH promoted their expression (P<0.01). Immunohistochemical staining indicated that 3MST existed in the neurons of pre-Bötzinger complex (pre-BötC), hypoglossal nucleus (12N), ambiguous nucleus (Amb), facial nucleus (FN) and nucleus tractus solitarius (NTS) in the animals and the mean optical densities of 3MST-positive neurons in the pre-BötC, 12N and Amb, but not in FN and NTS, were significantly increased in CIH group (P<0.05). In conclusion, 3MST exists in the neurons of medullary respiratory nuclei and its expression can be up-regulated by CIH in adult rat, suggesting that 3MST-H2S pathway may be involved in regulation of respiration and protection on medullary respiratory centers from injury induced by CIH. © 2013.

  14. Severe Sepsis Manifesting as A-Fib with Rapid Ventricular Rate

    Directory of Open Access Journals (Sweden)

    Paul Nicholson

    2018-01-01

    Full Text Available Audience: This simulation is designed to educate emergency medicine residents and medical students on the diagnosis and management of an adult patient with sepsis due to a decubitus ulcer manifesting as acute-onset atrial fibrillation (A-fib with rapid ventricular response (RVR. Introduction: Adult patients frequently present critically ill from sepsis. Proper diagnosis and management require a focused but thorough history and physical exam, as well as an appropriate diagnostic workup. Management includes aggressive care with antibiotics and intravenous fluids, and may require vasoactive agents. Objectives: Learners will be able to identify and manage atrial fibrillation with rapid ventricular response. Additionally, learners will be able to identify the concurrent infection and determine the appropriate management in the setting of A-fib with RVR. The case also provides learners with the opportunity to review principles of leadership, teamwork, and effective communication. Method: This session was conducted using high-fidelity simulation, followed by a debriefing session.

  15. Electroacupuncture Ameliorates Cognitive Deficit and Improves Hippocampal Synaptic Plasticity in Adult Rat with Neonatal Maternal Separation

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    Lili Guo

    2018-01-01

    Full Text Available Exposure to adverse early-life events is thought to be the risk factors for the development of psychiatric and altered cognitive function in adulthood. The purpose of this study was to investigate whether electroacupuncture (EA treatment in young adult rat would improve impaired cognitive function and synaptic plasticity in adult rat with neonatal maternal separation (MS. Wistar rats were randomly divided into four groups: control group, MS group, MS with EA treatment (MS + EA group, and MS with Sham-EA treatment (MS + Sham-EA group. We evaluated the cognitive function by using Morris water maze and fear conditioning tests. Electrophysiology experiment used in vivo long-term potentiation (LTP at Schaffer Collateral-CA1 synapses was detected to assess extent of synaptic plasticity. Repeated EA stimulation at Baihui (GV 20 and Yintang (GV 29 during postnatal 9 to 11 weeks was identified to significantly ameliorate poor performance in behavior tests and improve the impaired LTP induction detected at Schaffer Collateral-CA1 synapse in hippocampus. Collectively, the findings suggested that early-life stress due to MS may induce adult cognitive deficit associated with hippocampus, and EA in young adult demonstrated that its therapeutic efficacy may be via ameliorating deficit of hippocampal synaptic plasticity.

  16. A comparative study of myosin and its subunits in adult and neonatal-rat hearts and in rat heart cells from young and old cultures.

    OpenAIRE

    Ghanbari, H A; McCarl, R L

    1980-01-01

    A possible explanation for the decrease in myosin Ca2+-dependent ATPase activity as rat heart cells age in culture is presented. The subunit structure and enzyme kinetics of myosin from adult and neonatal rat hearts and from rat heart cells of young and old cultures are compared. These studies indicate that the loss in Ca-ATPase activity of myosin from older cultures was an intrinsic property of the myosin itself. Myofibrillar fractions from the indicated four sources showed no qualitative or...

  17. Negative Effect of Zinc on Testes, Testosterone and Gonadotrophins Levels in Adult Male Wistar Rats

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    D Sohrabi

    2012-05-01

    Full Text Available

    Background and Objectives

    The toxic effects of zinc leading to sebaceous gland closure, skin eczema and blister have been previously demonstrated in other studies. The aim of this study is to determine the chronic effects of zinc chloride (ZnCl2   on testicular tissues, testosterone and gonadotrophins in adult male Wistar rats.

     

    Methods

    Twenty four Adult male Wistar rats were divided in to two groups of study and control with each group consisting of 12 rats. Study group rats received 10 mg/kg interaperitoneal Zinc chloride in normal saline (N.S every other day for 30 days. Control group rats received N.S during this time. Blood sample for hormonal evaluation were collected from hearts of these rats. The rats were destroyed and their testes were removed and fixed in a 10% formaldehyde and glutaraldehyde solution.

     

    Results

    The results of this study showed a significant decrease in the level of LH and testosterone hormone among the rats in the study group compared to the control group with p< 0.001  and

    p< 0.01 respectively. Study of fine structure of testicular cells and tissues in the study group rats  revealed swelling of mitochondria, increase in smooth endoplasmic reticulum vacuolization and lysosomic granules (Autophagic vacuoles in cytosol of their germinal cells.

     

    Conclusion

    Based on the results of this study consumption of large amount of compounds which contain zinc should be controlled and limited among men. There is a need for further studies to evaluate and determine the reversibility of most hormonal and physiological changes due to usage of zinc containing compounds.

  18. Traditional Chinese Medicine Tongxinluo Improves Cardiac Function of Rats with Dilated Cardiomyopathy

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    Fang-Fang Shen

    2014-01-01

    Full Text Available The study aimed at testing the hypothesis that tongxinluo capsule might exert its cardioprotective effect by preventing ventricular remodeling and improving coronary microvascular function in a rat model of doxorubicin-induced dilated cardiomyopathy (DCM. Rats that survived DCM induction were randomly divided into three groups to be given 1.5 g·kg−1·day−1 (TXL-H, n=9 or 0.15 g·kg−1·day−1 (TXL-L, n=10 of tongxinluo, or normal saline at the same volume (DCM-C, n=10 intragastrically. Age matched normal rats treated with normal saline were used as normal controls (NOR-C, n=9. After four weeks of treatment, the DCM-C, TXL-H, and TXL-L groups exhibited significant cardiac dysfunction, left ventricular remodeling, and coronary microvascular dysfunction, compared with the NOR-C rats. However, myocardial functional parameters were significantly improved and microvascular density (MVD increased in the TXL-H group compared with the DCM-C group (all P<0.01. Left ventricular remodeling was prevented. There were close linear relationships between CVF and LVEF (r=-0.683, P<0.05, MVD and LVEF (r=0.895, P<0.05, and MVD and CVF (r=-0.798, P<0.05. It was indicated that high-dose tongxinluo effectively improved cardiac function in rat model of DCM.

  19. Inhibition of Rac1 reduces store overload-induced calcium release and protects against ventricular arrhythmia.

    Science.gov (United States)

    Zhang, Lili; Lu, Xiangru; Gui, Le; Wu, Yan; Sims, Stephen M; Wang, Guoping; Feng, Qingping

    2016-08-01

    Rac1 is a small GTPase and plays key roles in multiple cellular processes including the production of reactive oxygen species (ROS). However, whether Rac1 activation during myocardial ischaemia and reperfusion (I/R) contributes to arrhythmogenesis is not fully understood. We aimed to study the effects of Rac1 inhibition on store overload-induced Ca(2+) release (SOICR) and ventricular arrhythmia during myocardial I/R. Adult Rac1(f/f) and cardiac-specific Rac1 knockdown (Rac1(ckd) ) mice were subjected to myocardial I/R and their electrocardiograms (ECGs) were monitored for ventricular arrhythmia. Myocardial Rac1 activity was increased and ventricular arrhythmia was induced during I/R in Rac1(f/f) mice. Remarkably, I/R-induced ventricular arrhythmia was significantly decreased in Rac1(ckd) compared to Rac1(f/f) mice. Furthermore, treatment with Rac1 inhibitor NSC23766 decreased I/R-induced ventricular arrhythmia. Ca(2+) imaging analysis showed that in response to a 6 mM external Ca(2+) concentration challenge, SOICR was induced with characteristic spontaneous intracellular Ca(2+) waves in Rac1(f/f) cardiomyocytes. Notably, SOICR was diminished by pharmacological and genetic inhibition of Rac1 in adult cardiomyocytes. Moreover, I/R-induced ROS production and ryanodine receptor 2 (RyR2) oxidation were significantly inhibited in the myocardium of Rac1(ckd) mice. We conclude that Rac1 activation induces ventricular arrhythmia during myocardial I/R. Inhibition of Rac1 suppresses SOICR and protects against ventricular arrhythmia. Blockade of Rac1 activation may represent a new paradigm for the treatment of cardiac arrhythmia in ischaemic heart disease. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  20. Comparison of two surgical techniques for creating an acute myocardial infarct in rats

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    Luiz Guilherme Achcar Capriglione

    2014-12-01

    Full Text Available Objective: To perform a comparative assessment of two surgical techniques that are used creating an acute myocardial infarc by occluding the left anterior descending coronary artery in order to generate rats with a left ventricular ejection fraction of less than 40%. Methods: The study was completely randomized and comprised 89 halothane-anaesthetised rats, which were divided into three groups. The control group (SHAM comprised fourteen rats, whose left anterior descending coronary artery was not occluded. Group 1 (G1: comprised by 35 endotracheally intubated and mechanically ventilated rats, whose left anterior descending coronary artery was occluded. Group 2 (G2: comprised 40 rats being manually ventilated using a nasal respirator whose left anterior descending coronary artery was occluded. Other differences between the two techniques include the method of performing the thoracotomy and removing the pericardium in order to expose the heart, and the use of different methods and suture types for closing the thorax. Seven days after surgery, the cardiac function of all surviving rats was determined by echocardiography. Results: No rats SHAM group had progressed to death or had left ventricular ejection fraction less than 40%. Nine of the 16 surviving G1 rats (56.3% and six of the 20 surviving G2 rats (30% had a left ventricular ejection fraction of less than 40%. Conclusion: The results indicate a tendency of the technique used in G1 to be better than in G2. This improvement is probably due to the greater duration of the open thorax, which reduces the pressure over time from the surgeon, allowing occlusion of left anterior descending coronary artery with higher accuracy.

  1. Analgesia for early-life pain prevents deficits in adult anxiety and stress in rats.

    Science.gov (United States)

    Victoria, Nicole C; Karom, Mary C; Murphy, Anne Z

    2015-01-01

    Previous studies in rats have established that inflammatory pain experienced on the day of birth (P0) decreases sensitivity to acute noxious, anxiety- and stress-provoking stimuli. However, to date, the impact of early-life pain on adult responses to chronic stress is not known. Further, the ability of morphine, administered at the time of injury, to mitigate changes in adult behavioral and hormonal responses to acute or chronic stressors has not been examined. P0 male and female Sprague-Dawley rat pups were given an intraplantar injection of 1% carrageenan or handled in an identical manner in the presence or absence of morphine. As adults, rats that experienced early-life pain displayed decreased sensitivity to acute stressors, as indicated by increased time in the inner area of the Open Field, and increased latency to immobility and decreased time immobile in the Forced Swim Test (FST). An accelerated return of corticosterone to baseline was also observed. Morphine administration at the time of injury completely reversed this 'hyporesponsive' phenotype. By contrast, following 7 days of chronic variable stress, injured animals displayed a 'hyperresponsive' phenotype in that they initiated immobility and spent significantly more time immobile in the FST than controls. Responses to chronic stress were also rescued in animals that received morphine at the time of injury. These data suggest that analgesia for early-life pain prevents adult hyposensitivity to acute anxiety- and stress-provoking stimuli and increased vulnerability to chronic stress, and have important clinical implications for the management of pain in infants. © 2014 S. Karger AG, Basel.

  2. Primary cardiac tumor presenting as left ventricular outflow tract obstruction and complex arrhythmia.

    Science.gov (United States)

    Fries, R; Achen, S; O'Brien, M T; Jackson, N D; Gordon, S

    2017-10-01

    An adult female mixed breed dog presented for recurrent collapsing episodes over several weeks. Holter evaluation revealed periods of sinus arrest and echocardiography identified a soft tissue mass with subsequent severe dynamic obstruction of the left ventricular outflow tract. The patient was euthanized five days after presentation for severe dyspnea. Necropsy revealed an irregular mass circumferentially lining the left ventricular outflow tract as well as multiple myocardial metastases. The final diagnosis was an undifferentiated pleomorphic endocardial sarcoma. Published by Elsevier B.V.

  3. Regional ventricular performance and exercise training in children and young adults after repair of tetralogy of Fallot: randomized controlled pilot study.

    Science.gov (United States)

    Duppen, Nienke; Geerdink, Lianne M; Kuipers, Irene M; Bossers, Sjoerd S M; Koopman, Laurens P; van Dijk, Arie P J; Roos-Hesselink, Jolien W; De Korte, Chris L; Helbing, Willem A; Kapusta, Livia

    2015-04-01

    Public-health guidelines recommend patients with congenital heart disease to exercise. Studies have shown that patients with congenital heart disease can improve physical exercise capacity. The effect of training on regional ventricular performance has hardly been studied. We performed a pilot study to assess whether an exercise training program would result in adverse changes of regional ventricular performance in patients with corrected tetralogy of Fallot. Multicenter prospective randomized controlled pilot study in patients with tetralogy of Fallot aged 10 to 25 years. A 12-week standardized aerobic dynamic exercise training program (3 one-hour sessions per week) was used. Pre- and post-training cardiopulmonary exercise tests, MRI, and echocardiography, including tissue-Doppler imaging, were performed. Patients were randomized to the exercise group (n=28) or control group (n=20). One patient in the exercise group dropped out. Change in tissue-Doppler imaging parameters was similar in the exercise group and control group (change in right ventricle free wall peak velocity E' exercise group, 0.8±2.6 cm/s; control group, 0.9±4.1; peak velocity A' exercise group, 0.4±2.4 m/s; control group 4.6±18.1 cm/s). This randomized controlled pilot study provides preliminary data suggesting that regional ventricular performance is well maintained during 3-month aerobic dynamic exercise training in children and young adults with repaired tetralogy of Fallot. This information might help patients adhere to current public-health guidelines. URL: http//:www.trialregister.nl. Unique identifier: NTR2731. © 2015 American Heart Association, Inc.

  4. Aging influences multiple indices of oxidative stress in the heart of the Fischer 344/NNia x Brown Norway/BiNia rat.

    Science.gov (United States)

    Asano, Shinichi; Rice, Kevin M; Kakarla, Sunil; Katta, Anjaiah; Desai, Devashish H; Walker, Ernest M; Wehner, Paulette; Blough, Eric R

    2007-01-01

    We report the influence of aging on multiple markers of oxidative-nitrosative stress in the heart of adult (6-month), aged (30-month) and very aged (36-month) Fischer 344/NNiaHSd x Brown Norway/BiNia (F344/NXBN) rats. Compared to adult (6-month) hearts, indices of oxidative (superoxide anion [O2*-], 4-hydroxy-2-nonenal [4-HNE]) and nitrosative (protein nitrotyrosylation) stress were 34.1 +/- 28.1%, 186 +/- 28.1% and 94 +/- 5.8% higher, respectively, in 36-month hearts and these findings were highly correlated with increases in left ventricular wall thickness (r > 0.669; r > 0.710 and P lead to age-associated alterations in cardiac oxidative stress.

  5. Eating high fat chow decreases dopamine clearance in adolescent and adult male rats but selectively enhances the locomotor stimulating effects of cocaine in adolescents.

    Science.gov (United States)

    Baladi, Michelle G; Horton, Rebecca E; Owens, William A; Daws, Lynette C; France, Charles P

    2015-03-24

    Feeding conditions can influence dopamine neurotransmission and impact behavioral and neurochemical effects of drugs acting on dopamine systems. This study examined whether eating high fat chow alters the locomotor effects of cocaine and dopamine transporter activity in adolescent (postnatal day 25) and adult (postnatal day 75) male Sprague-Dawley rats. Dose-response curves for cocaine-induced locomotor activity were generated in rats with free access to either standard or high fat chow or restricted access to high fat chow (body weight matched to rats eating standard chow). Compared with eating standard chow, eating high fat chow increased the sensitivity of adolescent, but not adult, rats to the acute effects of cocaine. When tested once per week, sensitization to the locomotor effects of cocaine was enhanced in adolescent rats eating high fat chow compared with adolescent rats eating standard chow. Sensitization to cocaine was not different among feeding conditions in adults. When adolescent rats that previously ate high fat chow ate standard chow, sensitivity to cocaine returned to normal. As measured by chronoamperometry, dopamine clearance rate in striatum was decreased in both adolescent and adult rats eating high fat chow compared with age-matched rats eating standard chow. These results suggest that high fat diet-induced reductions in dopamine clearance rate do not always correspond to increased sensitivity to the locomotor effects of cocaine, suggesting that mechanisms other than dopamine transporter might play a role. Moreover, in adolescent but not adult rats, eating high fat chow increases sensitivity to cocaine and enhances the sensitization that develops to cocaine. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  6. Limitations and pitfalls in measurements of right ventricular stroke volume in an animal model of right heart failure

    International Nuclear Information System (INIS)

    Vildbrad, Mads Dam; Andersen, Asger; Andersen, Thomas Krarup; Axelgaard, Sofie; Holmboe, Sarah; Andersen, Stine; Nielsen-Kudsk, Jens Erik; Ringgaard, Steffen

    2015-01-01

    Right heart failure occurs in various heart and pulmonary vascular diseases and may be fatal. We aimed to identify limitations in non-invasive measurements of right ventricular stroke volume in an animal model of right ventricular failure. Data from previous studies randomising rats to pulmonary trunk banding (PTB, n = 33) causing pressure-overload right ventricular failure or sham operation (n = 16) was evaluated retrospectively. We measured right ventricular stroke volume by high frequency echocardiography and magnetic resonance imaging (MRI). We found correlation between right ventricular stroke volume measured by echocardiography and MRI in the sham animals (r = 0.677, p = 0.004) but not in the PTB group. Echocardiography overestimated the stroke volume compared to MRI in both groups. Intra- and inter-observer variation did not explain the difference. Technical, physiological and anatomical issues in the pulmonary artery might explain why echocardiography over-estimates stroke volume. Flow acceleration close to the pulmonary artery banding can cause uncertainties in the PTB model and might explain the lack of correlation. In conclusion, we found a correlation in right ventricular stroke volume measured by echocardiography versus MRI in the sham group but not the PTB group. Echocardiography overestimated right ventricular stroke volume compared to MRI. (paper)

  7. Neuroprotective Effect of Melatonin Against PCBs Induced Behavioural, Molecular and Histological Changes in Cerebral Cortex of Adult Male Wistar Rats.

    Science.gov (United States)

    Bavithra, S; Selvakumar, K; Sundareswaran, L; Arunakaran, J

    2017-02-01

    There is ample evidence stating Polychlorinated biphenyls (PCBs) as neurotoxins. In the current study, we have analyzed the behavioural impact of PCBs exposure in adult rats and assessed the simultaneous effect of antioxidant melatonin against the PCBs action. The rats were grouped into four and treated intraperitoneally with vehicle, PCBs, PCBs + melatonin and melatonin alone for 30 days, respectively. After the treatment period the rats were tested for locomotor activity and anxiety behaviour analysis. We confirmed the neuronal damage in the cerebral cortex by molecular and histological analysis. Our data indicates that there is impairment in locomotor activity and behaviour of PCBs treated rats compared to control. The simultaneous melatonin treated rat shows increased motor coordination and less anxiety like behaviour compared to PCBs treated rats. Molecular and histological analysis supports that, the impaired motor coordination in PCBs treated rats is due to neurodegeneration in motor cortex region. The results proved that melatonin treatment improved the motor co-ordination and reduced anxiety behaviour, prevented neurodegeneration in the cerebral cortex of PCBs-exposed adult male rats.

  8. HISTOLOGICAL STUDIES OF THE EFFECTS OF MONOSODIUM GLUTAMATE ON THE INFERIOR COLLICULUS OF ADULT WISTAR RATS.

    Directory of Open Access Journals (Sweden)

    A.O. Eweka.

    2008-01-01

    Full Text Available Histological effects of Monosodium glutamate (MSG commonly used as food additive on the inferior colliculus (IC of adult Wistar rats were carefully studied. The rats of both sexes (n=24, average weight of 185g were randomly assigned into two treatments (n=16 and control (n=8 groups. The rats in the treatment groups received 3g and 6g of MSG thoroughly mixed with their feeds for fourteen days, while the control rats received equal amounts of feeds without MSG added. The rats were fed with growers' mash purchased from Edo Feeds and Flour Mill Ltd, Ewu, Edo State and were given water liberally. The rats were sacrificed on day fifteen of the experiment. The inferior colliculus was carefully dissected out and quickly fixed in 10% formal saline for routine histological study after H&E method.The histological findings after H&E methods indicated that the treated sections of the inferior colliculus showed some cellular degenerative changes, cellular hypertrophy, and autophagic vacuoles with some intercellular vacuolations appearing in the stroma, and some degree of neuronal hypertrophy when compared to the control sections.These findings indicate that MSG consumption may have a deleterious effect on the neurons of the inferior colliculus (IC. MSG may probably have adverse effects on the auditory sensibilities by its deleterious effects on the nerve cells of the IC of adult Wistar rats. It is recommended that further studies aimed at corroborating these observations be carried out.

  9. HISTOLOGICAL EFFECTS OF CHRONIC CONSUMPTION OF NUTMEG ON THE LATERAL GENICULATE BODY OF ADULT WISTAR RATS.

    Directory of Open Access Journals (Sweden)

    J.O. Adjene

    2010-01-01

    Full Text Available The effects of chronic consumption of nutmeg commonly used as a spice in various dishes, as components of teas and soft drinks or mixed in milk and alcohol on the lateral geniculate body of adult wistar rats was studied.The rats of both sexes, with average weight of 200g were randomly assigned into treatment and control groups. The rats in the treatment group (n=8 received 2g of nutmeg thoroughly mixed with the feeds on a daily basis for thirty-two days. The control group (n=8 received equal amount of feeds daily without nutmeg added for thirty-two days. The growers mash feeds was obtained from Edo Feeds and Flour Mill Limited, Ewu, Edo State, Nigeria and the rats were given water liberally. The rats were sacrificed on the thirty-three day of the experiment. The lateral geniculate body was carefully dissected out and quickly fixed in 10% formal saline for histological study.The findings indicate that rats in the treated group showed some cellular degenerative changes like sparse cellular population, pyknotic nuclei with some microcystic changes, edema and vacuolations in the stroma of the treated lateral geniculate body as compared to that of the control group.Chronic consumption of nutmeg may therefore have an adverse effect on the visual sensibilities by affecting the microanatomy of the lateral geniculate body of adult wistar rats. It is recommended for further studies aimed at corroborating these observations.

  10. Cortex-dependent recovery of unassisted hindlimb locomotion after complete spinal cord injury in adult rats

    Science.gov (United States)

    Manohar, Anitha; Foffani, Guglielmo; Ganzer, Patrick D; Bethea, John R; Moxon, Karen A

    2017-01-01

    After paralyzing spinal cord injury the adult nervous system has little ability to ‘heal’ spinal connections, and it is assumed to be unable to develop extra-spinal recovery strategies to bypass the lesion. We challenge this assumption, showing that completely spinalized adult rats can recover unassisted hindlimb weight support and locomotion without explicit spinal transmission of motor commands through the lesion. This is achieved with combinations of pharmacological and physical therapies that maximize cortical reorganization, inducing an expansion of trunk motor cortex and forepaw sensory cortex into the deafferented hindlimb cortex, associated with sprouting of corticospinal axons. Lesioning the reorganized cortex reverses the recovery. Adult rats can thus develop a novel cortical sensorimotor circuit that bypasses the lesion, probably through biomechanical coupling, to partly recover unassisted hindlimb locomotion after complete spinal cord injury. DOI: http://dx.doi.org/10.7554/eLife.23532.001 PMID:28661400

  11. Ghrelin modulates testicular germ cells apoptosis and proliferation in adult normal rats

    Energy Technology Data Exchange (ETDEWEB)

    Kheradmand, Arash, E-mail: arashkheradmand@yahoo.com [Department of Clinical Sciences, School of Veterinary Medicine, Lorestan University, P.O. Box: 465, Khorram Abad (Iran, Islamic Republic of); Dezfoulian, Omid [Department of Pathobiology, School of Veterinary Medicine, Lorestan University, Khorram Abad (Iran, Islamic Republic of); Alirezaei, Masoud [Division of Biochemistry, School of Veterinary Medicine, Lorestan University, P.O. Box: 465, Khorram Abad (Iran, Islamic Republic of); Rasoulian, Bahram [Razi Herbal Medicine Research Center, Lorestan University of Medical Sciences, Khorram Abad (Iran, Islamic Republic of)

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer Spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. Black-Right-Pointing-Pointer Numerous studies have documented the direct action of ghrelin in the modulation of apoptosis in different cell types. Black-Right-Pointing-Pointer Ghrelin may be considered as a modulator of spermatogenesis in normal adult rats. Black-Right-Pointing-Pointer Ghrelin may be potentially implicated for abnormal spermatogenesis in some testicular germ cell tumors. -- Abstract: Under normal condition in the most mammals, spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. The present study was designed to determine the effects of ghrelin treatment on in vivo quality and quantity expression of apoptosis and proliferation specific indices in rat testicular germ cells. Twenty eight adult normal rats were subdivided into equal control and treatment groups. Treatment group received 3 nmol of ghrelin as subcutaneous injection for 30 consecutive days or vehicle to the control animals. The rats from each group (n = 7) were killed on days 10 and 30 and their testes were taken for immunocytochemical evaluation and caspase-3 assay. Immunohistochemical analysis indicated that the accumulations of Bax and PCNA peptides are generally more prominent in spermatocytes and spermatogonia of both groups. Likewise, the mean percentage of immunoreactive spermatocytes against Bax increased (P < 0.01) in the ghrelin-treated group on day 10, while despite of 30% increment in the Bax level of spermatocytes in the treated rats on day 30, however, it was not statistically significant. During the experimental period, only a few spermatogonia represented Bax expression and the changes of Bax immunolabling cells were negligible upon ghrelin treatment. Likewise, there were immunostaining cells against Bcl-2 in each germ cell neither in the control nor in the treated animals. In fact

  12. Serial Noninvasive Assessment of Apoptosis During Right Ventricular Disease Progression in Rats

    NARCIS (Netherlands)

    Campian, Maria E.; Verberne, Hein J.; Hardziyenka, Maxim; de Bruin, Kora; Selwaness, Mariana; van den Hoff, Maurice J. B.; Ruijter, Jan M.; van Eck-Smit, Berthe L. F.; de Bakker, Jacques M. T.; Tan, Hanno L.

    2009-01-01

    Right ventricular (RV) function is the major determinant of survival in patients with pulmonary hypertension. Yet, the pathophysiologic basis of RV disease is unresolved. We aimed to study the role of apoptosis in RV disease by monitoring it serially during disease progression using in vivo

  13. Persistent changes in ability to express long-term potentiation/depression in the rat hippocampus after juvenile/adult stress.

    Science.gov (United States)

    Maggio, Nicola; Segal, Menahem

    2011-04-15

    The ventral hippocampus (VH) was recently shown to express lower magnitude long-term potentiation (LTP) compared with the dorsal hippocampus (DH). Exposure to acute stress reversed this difference, and VH slices from stressed rats expressed larger LTP than that produced in the DH, which was reduced by stress. Stressful experience in adolescence has been shown to produce long-lasting effects on animal behavior and on ability to express LTP/long-term depression (LTD) of reactivity to afferent stimulation in the adult. We are interested in possible interactions between juvenile and adult stress in their effects of adult plasticity. We studied the effects of a composite juvenile (28-30 days) stress, followed by a reminder stressful experience in the young adult (60 days) rat, on the ability to produce LTP and LTD in CA1 region of slices of the VH and DH. Juvenile or adult stress produced a transient decrease in ability to express LTP in DH and a parallel increase in LTP in VH. Stress in the young adult after juvenile stress produced a striking prolongation of the DH/VH disparity with respect to the ability to express both LTP and LTD into the adulthood of the rat. These results have important implications for the impact of juvenile stress on adult neuronal plasticity and on the understanding the functions of the different sectors of the hippocampus. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  14. Stress induced right ventricular dysfunction: An indication of reversible right ventricular ischaemia

    International Nuclear Information System (INIS)

    Underwood, S.R.; Walton, S.; Emanuel, R.W.; Swanton, R.H.; Campos Costa, D.; Laming, P.J.; Ell, P.J.

    1987-01-01

    Stress induced changes in left ventricular ejection fraction are widely used in the detection and assessment of coronary artery disease. This study demonstrates that right ventricular dysfunction may also occur, and assesses its significance in terms of coronary artery anatomy. This study involved 14 normal subjects and 26 with coronary artery disease investigated by equilibrium radionuclide ventriculography, at rest and during maximal dynamic exercise. Mean normal resting right ventricular ejection fraction (RVEF) was 0.40 (SD 0.118), and all normal subjects increased RVEF with stress (mean ΔRVEF+0.13 SD 0.099). Mean ΔRVEF in the subjects with coronary artery disease was significantly lower at 0.00 (SD 0.080), but there was overlap between the two groups. The largest falls in RVEF were seen if the right coronary artery was occluded without retrograde filling. In this subgroup with the most severely compromised right ventricular perfusion (nine subjects), RVEF always fell with stress, and mean ΔRVEF was -0.08 (SD 0.050). There was no significant correlation between ΔLVEF and ΔRVEF, implying that the right ventricular dysfunction was due to right ventricular ischaemia, rather than secondary to left ventricular dysfunction. Stress induced right ventricular ischaemia can therefore be detected readily by radionuclide ventriculography. (orig.)

  15. Mitogen response of B cells, but not T cells, is impaired in adult vitamin A-deficient rats

    NARCIS (Netherlands)

    van Bennekum, A. M.; Wong Yen Kong, L. R.; Gijbels, M. J.; Tielen, F. J.; Roholl, P. J.; Brouwer, A.; Hendriks, H. F.

    1991-01-01

    The effect of vitamin A deficiency on the mitogen response of splenic B and T lymphocytes was determined in adult vitamin A-deficient rats. Female weanling Brown Norway/Billingham-Rijswijk (BN/BiRij) and Sprague-Dawley rats were fed a semipurified, essentially vitamin A-free diet, which resulted in

  16. A combined phytohemagglutinin and a-ketoglutarate pharmacology study of gut morphology and growth in older adult rats

    DEFF Research Database (Denmark)

    Filip, R.; Harrison, Adrian Paul; Pierzynowski, S.G.

    2008-01-01

    This study has evaluated the effect of phytohaemagglutinin (PHA) in combination with alpha-ketoglutaric acid (AKG), on GI-tract morphology and N balance in adult rats. Rats, aged approx. 15 months, were assigned to one of four experimental groups, (1) Control group, (2) AKG group, (3) AKG+PHA 100...

  17. Pattern of chondroitin sulfate proteoglycan expression after ablation of the sensorimotor cortex of the neonatal and adult rat brain

    Directory of Open Access Journals (Sweden)

    Dacić Sanja

    2008-01-01

    Full Text Available The central nervous system has a limited capacity for self-repair after damage. However, the neonatal brain has agreater capacity for recovery than the adult brain. These differences in the regenerative capability depend on local environmental factors and the maturational stage of growing axons. Among molecules which have both growth-promoting and growth-inhibiting activities is the heterogeneous class of chondroitin sulfate proteoglycans (CSPGs. In this paper, we investigated the chondroitin-4 and chondroitin-6 sulfate proteoglycan expression profile after left sensorimotor cortex ablation of the neonatal and adult rat brain. Immunohistochemical analysis revealed that compared to the normal uninjured cortex, lesion provoked up regulation of CSPGs showing a different pattern of expression in the neonatal vs. the adult brain. Punctuate and membrane-bound labeling was predominate after neonatal lesion, where as heavy deposition of staining in the extracellular matrix was observed after adult lesion. Heavy deposition of CSPG immunoreactivity around the lesionsite in adult rats, in contrast to a less CSPG-rich environment in neonatal rats, indicated that enhancement of the recovery process after neonatal injury is due to amore permissive environment.

  18. Electroconvulsive Stimulation, but not Chronic Restraint Stress, Causes Structural Alterations in Adult Rat Hippocampus

    DEFF Research Database (Denmark)

    Olesen, Mikkel V.; Wörtwein, Gitta; Pakkenberg, Bente

    2015-01-01

    The neurobiological mechanisms underlying depression are not fully understood. Only a few previous studies have used validated stereological methods to test how stress and animal paradigms of depression affect adult hippocampal neurogenesis and whether antidepressant therapy can counteract possible...... changes in an animal model. Thus, in this study we applied methods that are state of the art in regard to stereological cell counting methods. Using a validated rat model of depression in combination with a clinically relevant schedule of electroconvulsive stimulation, we estimated the total number...... of newly formed neurons in the hippocampal subgranular zone. Also estimated were the total number of neurons and the volume of the granule cell layer in adult rats subjected to chronic restraint stress and electroconvulsive stimulation either alone or in combination. We found that chronic restraint stress...

  19. Indications for CSF shunting in normal pressure hydrocephalus following subarachnoid hemorrhage with lateral ventricular size change on cine-MR

    Energy Technology Data Exchange (ETDEWEB)

    Fujitsuka, Mitsuyuki [Kyorin Univ., Mitaka, Tokyo (Japan). School of Medicine

    2002-09-01

    To clarify the indications for cerebrospinal fluid (CSF) shunting in normal pressure hydrocephalus (NPH) following subarachnoid hemorrhage (SAH), the author investigated changes in the pulsatile brain motions during a cardiac cycle in 17 cases with ventriculomegaly following SAH on cardiac gated cine MR images comparing with those in 50 normal adults. In 15 of these seventeen cases, the lateral ventricles not only constricted immediately following the R-wave related to brain expansion but also expanded paradoxically over the initial size during a cardiac diastole. These patterns were different from those of normal adults, and eleven of them showed excellent response to CSF shunting. Theses findings in ventricular motion during a cardiac cycle indicate that the forceful intraventricular CSF flows and stagnancy expand the ventricular walls causing compression of the surrounding brain against the skull. In the remaining two, the lateral ventricles only constricted immediately following the R-wave and the ventricular size change was similar to those of normal adults, and they were diagnosed as not requiring CSF shunting. Assessing ventricular size change on cine-MR enables non-invasive differentiation of NPH from other form of ventriculomegaly, and evaluation of the benefit of CSF shunting is also possible by this technique preoperatively. (author)

  20. Dynamic Action Potential Restitution Contributes to Mechanical Restitution in Right Ventricular Myocytes From Pulmonary Hypertensive Rats.

    Science.gov (United States)

    Hardy, Matthew E L; Pervolaraki, Eleftheria; Bernus, Olivier; White, Ed

    2018-01-01

    We investigated the steepened dynamic action potential duration (APD) restitution of rats with pulmonary artery hypertension (PAH) and right ventricular (RV) failure and tested whether the observed APD restitution properties were responsible for negative mechanical restitution in these myocytes. PAH and RV failure were provoked in male Wistar rats by a single injection of monocrotaline (MCT) and compared with saline-injected animals (CON). Action potentials were recorded from isolated RV myocytes at stimulation frequencies between 1 and 9 Hz. Action potential waveforms recorded at 1 Hz were used as voltage clamp profiles (action potential clamp) at stimulation frequencies between 1 and 7 Hz to evoke rate-dependent currents. Voltage clamp profiles mimicking typical CON and MCT APD restitution were applied and cell shortening simultaneously monitored. Compared with CON myocytes, MCT myocytes were hypertrophied; had less polarized diastolic membrane potentials; had action potentials that were triggered by decreased positive current density and shortened by decreased negative current density; APD was longer and APD restitution steeper. APD90 restitution was unchanged by exposure to the late Na + -channel blocker (5 μM) ranolazine or the intracellular Ca 2+ buffer BAPTA. Under AP clamp, stimulation frequency-dependent inward currents were smaller in MCT myocytes and were abolished by BAPTA. In MCT myocytes, increasing stimulation frequency decreased contraction amplitude when depolarization duration was shortened, to mimic APD restitution, but not when depolarization duration was maintained. We present new evidence that the membrane potential of PAH myocytes is less stable than normal myocytes, being more easily perturbed by external currents. These observations can explain increased susceptibility to arrhythmias. We also present novel evidence that negative APD restitution is at least in part responsible for the negative mechanical restitution in PAH myocytes. Thus

  1. The H{sub 1}–H{sub 2} domain of the α{sub 1} isoform of Na{sup +}–K{sup +}–ATPase is involved in ouabain toxicity in rat ventricular myocytes

    Energy Technology Data Exchange (ETDEWEB)

    Xiong, Chen; Li, Jun-xia; Guo, Hui-cai; Zhang, Li-nan; Guo, Wei; Meng, Jing; Wang, Yong-li, E-mail: wangyongli@gmail.com

    2012-07-01

    The composition of different isoforms of Na{sup +}-K{sup +}-ATPase (NKA, Na/K pump) in ventricular myocytes is an important factor in determining the therapeutic effect and toxicity of cardiac glycosides (CGs) on heart failure. The mechanism whereby CGs cause these effects is still not completely clear. In the present study, we prepared two site-specific antibodies (SSA78 and WJS) against the H{sub 1}–H{sub 2} domain of α{sub 1} and α{sub 2} isoforms of NKA in rat heart, respectively, and compared their influences on the effect of ouabain (OUA) in isolated rat ventricular myocytes. SSA78 or WJS, which can specifically bind with the α{sub 1} or α{sub 2} isoform, were assessed with enzyme linked immunosorbent assay (ELISA), Western blot and immunofluorescent staining methods. Preincubation of myocytes with SSA78 inhibited low OUA affinity pump current but not high OUA affinity pump current, reduced the rise in cytosolic calcium concentration ([Ca{sup 2+}]{sub i}), attenuated mitochondrial Ca{sup 2+} overload, restored mitochondrial membrane potential reduction, and delayed the decrease of the myocardial contractile force as well as the occurrence of arrhythmic contraction induced by high concentrations (1 mM) but not low concentrations (1 μM) of OUA. Similarly, preincubation of myocytes with WJS inhibited high OUA affinity pump current, reduced the increase of [Ca{sup 2+}]{sub i} and the contractility induced by 1 μM but not that induced by 1 mM OUA. These results indicate that the H{sub 1}–H{sub 2} domain of the NKA α{sub 1} isoform mediates OUA-induced cardiac toxicity in rat ventricular myocytes, and inhibitors for this binding site may be used as an adjunct to CGs treatment for cardiovascular disease. -- Highlights: ► We prepared two antibodies against the H{sub 1}-H{sub 2} domain of α{sub 1} and α{sub 2} isoforms of NKA. ► The H{sub 1}-H{sub 2} domain of the NKA α{sub 1} isoform mediates OUA-induced cardiac toxicity. ► The H{sub 1}-H{sub 2

  2. Differential cardiac effects in rats exposed to atmospheric ...

    Science.gov (United States)

    The results of this study demonstrate that atmospheric smog generated from both isoprene and toluene cause cardiac effects in rats. In addition, it appears that smog from toluene is more toxic in terms of cardiac arrhythmogenicity. Smog, which is a complex mixture of particulate matter and gaseous irritants (ozone, sulfur dioxide, reactive aldehydes), as well as components which react with sunlight to form secondary pollutants, has recently been linked to increased risk of adverse cardiac responses. The components, and therefore health effects, of atmospheric smog are determined by the fuel used to generate them. In this study we examined the difference between isoprene- and toluene-generated smog in causing cardiac effects in rats and hypothesized that both atmospheres would cause cardiac electrical and functional changes in rats. Male Wistar-Kyoto rats were exposed to either atmospheric smog generated by the USEPA’s mobile reaction chamber using either isoprene or toluene, or filtered air for four hours. One day later, rats were anesthetized and left ventricular functional responses to dobutamine were measured using a Millar probe and arrhythmia sensitivity to aconitine. Baseline left ventricular pressure (LVP) was lower in toluene-exposed animals but not isoprene when compared to air. Increases in LVP with increasing doses of dobutamine were impaired only in toluene-exposed rats. Both isoprene and toluene impaired the rate of ventri

  3. Systolic ventricular filling.

    Science.gov (United States)

    Torrent-Guasp, Francisco; Kocica, Mladen J; Corno, Antonio; Komeda, Masashi; Cox, James; Flotats, A; Ballester-Rodes, Manel; Carreras-Costa, Francesc

    2004-03-01

    The evidence of the ventricular myocardial band (VMB) has revealed unavoidable coherence and mutual coupling of form and function in the ventricular myocardium, making it possible to understand the principles governing electrical, mechanical and energetical events within the human heart. From the earliest Erasistratus' observations, principal mechanisms responsible for the ventricular filling have still remained obscured. Contemporary experimental and clinical investigations unequivocally support the attitude that only powerful suction force, developed by the normal ventricles, would be able to produce an efficient filling of the ventricular cavities. The true origin and the precise time frame for generating such force are still controversial. Elastic recoil and muscular contraction were the most commonly mentioned, but yet, still not clearly explained mechanisms involved in the ventricular suction. Classical concepts about timing of successive mechanical events during the cardiac cycle, also do not offer understandable insight into the mechanism of the ventricular filling. The net result is the current state of insufficient knowledge of systolic and particularly diastolic function of normal and diseased heart. Here we summarize experimental evidence and theoretical backgrounds, which could be useful in understanding the phenomenon of the ventricular filling. Anatomy of the VMB, and recent proofs for its segmental electrical and mechanical activation, undoubtedly indicates that ventricular filling is the consequence of an active muscular contraction. Contraction of the ascendent segment of the VMB, with simultaneous shortening and rectifying of its fibers, produces the paradoxical increase of the ventricular volume and lengthening of its long axis. Specific spatial arrangement of the ascendent segment fibers, their interaction with adjacent descendent segment fibers, elastic elements and intra-cavitary blood volume (hemoskeleton), explain the physical principles

  4. Physiological Stress Elicits Impaired Left Ventricular Function in Preterm-Born Adults.

    Science.gov (United States)

    Huckstep, Odaro J; Williamson, Wilby; Telles, Fernando; Burchert, Holger; Bertagnolli, Mariane; Herdman, Charlotte; Arnold, Linda; Smillie, Robert; Mohamed, Afifah; Boardman, Henry; McCormick, Kenny; Neubauer, Stefan; Leeson, Paul; Lewandowski, Adam J

    2018-03-27

    Experimental and clinical studies show that prematurity leads to altered left ventricular (LV) structure and function with preserved resting LV ejection fraction (EF). Large-scale epidemiological data now links prematurity to increased early heart failure risk. The authors performed echocardiographic imaging at prescribed exercise intensities to determine whether preterm-born adults have impaired LV functional response to physical exercise. We recruited 101 normotensive young adults born preterm (n = 47; mean gestational age 32.8 ± 3.2 weeks) and term (n = 54) for detailed cardiovascular phenotyping. Full clinical resting and exercise stress echocardiograms were performed, with apical 4-chamber views collected while exercising at 40%, 60%, and 80% of peak exercise capacity, determined by maximal cardiopulmonary exercise testing. Preterm-born individuals had greater LV mass (p = 0.015) with lower peak systolic longitudinal strain (p = 0.038) and similar EF to term-born control subjects at rest (p = 0.62). However, by 60% exercise intensity, EF was 6.7% lower in preterm subjects (71.9 ± 8.7% vs 78.6 ± 5.4%; p = 0.004) and further declined to 7.3% below the term-born group at 80% exercise intensity (69.8 ± 6.4% vs 77.1 ± 6.3%; p = 0.004). Submaximal cardiac output reserve was 56% lower in preterm-born subjects versus term-born control subjects at 40% of peak exercise capacity (729 ± 1,162 ml/min/m 2 vs. 1,669 ± 937 ml/min/m 2 ; p = 0.021). LV length and resting peak systolic longitudinal strain predicted EF increase from rest to 60% exercise intensity in the preterm group (r = 0.68, p = 0.009 and r = 0.56, p = 0.031, respectively). Preterm-born young adults had impaired LV response to physiological stress when subjected to physical exercise, which suggested a reduced myocardial functional reserve that might help explain their increased risk of early heart failure. (Young Adult Cardiovascular Health sTudy [YACHT]; NCT02103231

  5. Trading new neurons for status: Adult hippocampal neurogenesis in eusocial Damaraland mole-rats.

    Science.gov (United States)

    Oosthuizen, M K; Amrein, I

    2016-06-02

    Diversity in social structures, from solitary to eusocial, is a prominent feature of subterranean African mole-rat species. Damaraland mole-rats are eusocial, they live in colonies that are characterized by a reproductive division of labor and a subdivision into castes based on physiology and behavior. Damaraland mole-rats are exceptionally long lived and reproductive animals show delayed aging compared to non-reproductive animals. In the present study, we described the hippocampal architecture and the rate of hippocampal neurogenesis of wild-derived, adult Damaraland mole-rats in relation to sex, relative age and social status or caste. Overall, Damaraland mole-rats were found to have a small hippocampus and low rates of neurogenesis. We found no correlation between neurogenesis and sex or relative age. Social status or caste was the most prominent modulator of neurogenesis. An inverse relationship between neurogenesis and social status was apparent, with queens displaying the lowest neurogenesis while the worker mole-rats had the most. As there is no natural progression from one caste to another, social status within a colony was relatively stable and is reflected in the level of neurogenesis. Our results correspond to those found in the naked mole-rat, and may reflect an evolutionary and environmentally conserved trait within social mole-rat species. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  6. Neonatal bee venom exposure induces sensory modality-specific enhancement of nociceptive response in adult rats.

    Science.gov (United States)

    Li, Mengmeng; Chen, Huisheng; Tang, Jiaguang; Chen, Jun

    2014-06-01

    Previous studies have shown that inflammatory pain at the neonatal stage can produce long-term structural and functional changes in nociceptive pathways, resulting in altered pain perception in adulthood. However, the exact pattern of altered nociceptive response and associated neurochemical changes in the spinal cord in this process is unclear. In this study, we used an experimental paradigm in which each rat first received intraplantar bee venom (BV) or saline injection on postnatal day 1, 4, 7, 14, 21, or 28. This was followed 2 months later by a second intraplantar bee venom injection in the same rats to examine the difference in nociceptive responses. We found that neonatal inflammatory pain induced by the first BV injection significantly reduced baseline paw withdrawal mechanical threshold, but not baseline paw withdrawal thermal latency, when rats were examined 2 months from the first BV injection. Neonatal inflammatory pain also exacerbated mechanical, but not thermal, hyperalgesia in response to the second BV injection in these same rats. Rats exposed to neonatal inflammation also showed up-regulation of spinal NGF, TrkA receptor, BDNF, TrkB receptor, IL-1β, and COX-2 expression following the second BV injection, especially with prior BV exposure on postnatal day 21 or 28. These results indicate that neonatal inflammation produces sensory modality-specific changes in nociceptive behavior and alters neurochemistry in the spinal cord of adult rats. These results also suggest that a prior history of inflammatory pain during the developmental period might have an impact on clinical pain in highly susceptible adult patients. Wiley Periodicals, Inc.

  7. Experience With a Long-term Pulsatile Ventricular Assist Device as a Bridge to Heart Transplant in Adults.

    Science.gov (United States)

    Gómez Bueno, Manuel; Segovia Cubero, Javier; Serrano Fiz, Santiago; Ugarte Basterrechea, Juan; Hernández Pérez, Francisco José; Goirigolzarri Artaza, Josebe; Castedo Mejuto, Evaristo; Burgos Lázaro, Raúl; García Montero, Carlos; Moñivas Palomero, Vanessa; Mingo Santos, Susana; González Román, Ana Isabel; Álvarez Avelló, José Manuel; Vidal Fernández, Mercedes; Forteza Gil, Alberto; Alonso-Pulpón, Luis

    2017-09-01

    Most long-term ventricular assist devices (VADs) that are currently implanted are intracorporeal continuous-flow devices. Their main limitations include their high cost and inability to provide biventricular support. The aim of this study was to describe the results of using paracorporeal pulsatile-flow VADs as a bridge to transplant (BTT) in adult patients. Retrospective analysis of the characteristics, complications, and outcomes of a single-center case series of consecutive patients treated with the EXCOR VAD as BTT between 2009 and 2015. During the study period, 25 VADs were implanted, 6 of them biventricular. Ventricular assist devices were indicated directly as a BTT in 12 patients and as a bridge to decision in 13 due to the presence of potentially reversible contraindications or chance of heart function recovery. Twenty patients (80%) were successfully bridged to heart transplant after a median of 112 days (range, 8-239). The main complications included infectious (52% of patients), neurological events (32%, half of them fatal), bleeding (28%), and VAD malfunction requiring component replacement (28%). Eighty percent of patients with the EXCOR VAD as BTT achieved the goal after an average of almost 4 months of support. The most frequent complications were infectious, and the most severe were neurological. In our enivonment, the use of these pulsatile-flow VAD as BTT is a feasible strategy that obtains similar outcomes to those of intracorporeal continuous-flow devices. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  8. Hypothyroidism in the adult rat causes incremental changes in brain-derived neurotrophic factor, neuronal and astrocyte apoptosis, gliosis, and deterioration of postsynaptic density.

    Science.gov (United States)

    Cortés, Claudia; Eugenin, Eliseo; Aliaga, Esteban; Carreño, Leandro J; Bueno, Susan M; Gonzalez, Pablo A; Gayol, Silvina; Naranjo, David; Noches, Verónica; Marassi, Michelle P; Rosenthal, Doris; Jadue, Cindy; Ibarra, Paula; Keitel, Cecilia; Wohllk, Nelson; Court, Felipe; Kalergis, Alexis M; Riedel, Claudia A

    2012-09-01

    Adult hypothyroidism is a highly prevalent condition that impairs processes, such as learning and memory. Even though tetra-iodothyronine (T(4)) treatment can overcome the hypothyroidism in the majority of cases, it cannot fully recover the patient's learning capacity and memory. In this work, we analyzed the cellular and molecular changes in the adult brain occurring with the development of experimental hypothyroidism. Adult male Sprague-Dawley rats were treated with 6-propyl-2-thiouracil (PTU) for 20 days to induce hypothyroidism. Neuronal and astrocyte apoptosis were analyzed in the hippocampus of control and hypothyroid adult rats by confocal microscopy. The content of brain-derived neurotrophic factor (BDNF) was analyzed using enzyme-linked immunosorbent assay (ELISA) and in situ hybridization. The glutamatergic synapse and the postsynaptic density (PSD) were analyzed by electron microscopy. The content of PSD proteins like tyrosine receptor kinase B (TrkB), p75, and N-methyl-D-aspartate receptor (NMDAr) were analyzed by immunoblot. We observed that the hippocampus of hypothyroid adult rats displayed increased apoptosis levels in neurons and astrocyte and reactive gliosis compared with controls. Moreover, we found that the amount of BDNF mRNA was higher in the hippocampus of hypothyroid rats and the content of TrkB, the receptor for BDNF, was reduced at the PSD of the CA3 region of hypothyroid rats, compared with controls. We also observed that the glutamatergic synapses from the stratum radiatum of CA3 from hypothyroid rats, contained thinner PSDs than control rats. This observation was in agreement with a reduced content of NMDAr subunits at the PSD in hypothyroid animals. Our data suggest that adult hypothyroidism affects the hippocampus by a mechanism that alters the composition of PSD, reduces neuronal and astrocyte survival, and alters the content of the signaling neurotrophic factors, such as BDNF.

  9. Percutaneous absorption of triadimefon in the adult and young male and female rat

    International Nuclear Information System (INIS)

    Knaak, J.B.; Yee, K.; Ackerman, C.R.; Zweig, G.; Wilson, B.W.

    1984-01-01

    The percutaneous absorption of 14 C-phenoxy ring labeled triadimefon was studied in adult and young male and female Sprague-Dawley rats. Triadimefon was applied (41.1 to 46.4 micrograms/cm2) in 0.2 ml of acetone to areas comprising 3% of the body surface (7.0 to 14.5 cm2). Thirty-six animals were treated at the initiation of each study. Groups of three animals were subsequently killed at 1, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hr after treatment. Skin from the treated area as well as blood, heart, liver, kidneys, remaining carcass, urine, and feces were analyzed for 14 C by scintillation counting techniques. Based on 14 C counts, triadimefon was lost more rapidly from the skin of young animals (t 1/2, 20 to 25 hr) than from the skin of adult animals (t 1/2, 29 to 53 hr). Recovery studies indicated that adult males, adult females, young males, and young females, respectively, absorbed 53, 82, 57, and 52% of the dose. The rest of the dose based on material balance was presumably lost by evaporation. Approximately 2.5 to 3.9% of the dose penetrated the skin in one hour and was available for absorption. The rate of entry triadimefon into blood was 2 to 2.5 times faster for young than that observed in adult animals. Elimination of it from blood was faster in the case of the young animals. Triadimefon was absorbed through the skins of the adult male, adult female, young male, and young female rats, respectively, at rates of 0.20, 0.50, 0.58, and 0.48 micrograms/hr/cm2 of skin

  10. Inhibition of cyclooxygenase-2 reduces hypothalamic excitation in rats with adriamycin-induced heart failure.

    Directory of Open Access Journals (Sweden)

    Min Zheng

    Full Text Available BACKGROUND: The paraventricular nucleus (PVN of the hypothalamus plays an important role in the progression of heart failure (HF. We investigated whether cyclooxygenase-2 (COX-2 inhibition in the PVN attenuates the activities of sympathetic nervous system (SNS and renin-angiotensin system (RAS in rats with adriamycin-induced heart failure. METHODOLOGY/PRINCIPAL FINDING: Heart failure was induced by intraperitoneal injection of adriamycin over a period of 2 weeks (cumulative dose of 15 mg/kg. On day 19, rats received intragastric administration daily with either COX-2 inhibitor celecoxib (CLB or normal saline. Treatment with CLB reduced mortality and attenuated both myocardial atrophy and pulmonary congestion in HF rats. Compared with the HF rats, ventricle to body weight (VW/BW and lung to body weight (LW/BW ratios, heart rate (HR, left ventricular end-diastolic pressure (LVEDP, left ventricular peak systolic pressure (LVPSP and maximum rate of change in left ventricular pressure (LV±dp/dtmax were improved in HF+CLB rats. Angiotensin II (ANG II, norepinephrine (NE, COX-2 and glutamate (Glu in the PVN were increased in HF rats. HF rats had higher levels of ANG II and NE in plasma, higher level of ANG II in myocardium, and lower levels of ANP in plasma and myocardium. Treatment with CLB attenuated these HF-induced changes. HF rats had more COX-2-positive neurons and more corticotropin releasing hormone (CRH positive neurons in the PVN than did control rats. Treatment with CLB decreased COX-2-positive neurons and CRH positive neurons in the PVN of HF rats. CONCLUSIONS: These results suggest that PVN COX-2 may be an intermediary step for PVN neuronal activation and excitatory neurotransmitter release, which further contributes to sympathoexcitation and RAS activation in adriamycin-induced heart failure. Treatment with COX-2 inhibitor attenuates sympathoexcitation and RAS activation in adriamycin-induced heart failure.

  11. Sex differences in ventricular-vascular coupling following endurance training.

    Science.gov (United States)

    Lane, A D; Yan, H; Ranadive, S M; Kappus, R M; Sun, P; Cook, M D; Harvey, I; Woods, J; Wilund, K; Fernhall, B

    2014-12-01

    Ventricular and vascular coupling is defined as the ratio of arterial elastance (Ea) to ventricular elastance (Elv) and describes the interaction between the heart and arterial system. There are sex differences in both arterial and ventricular function in response to both acute exercise and aerobic exercise training. To examine the effects of aerobic exercise training on elastances and the coupling ratio in young adult men and women. We hypothesized a reduction in the coupling ratio in both sexes due to a decrease in Ea that would be more pronounced in men and an increase in Elv that would be larger in women. Fifty-three healthy, young adults completed the study. Central pulse wave velocity and heart volumes were measured before and after an 8-week aerobic training intervention. Elastances were calculated as Ea = end-systolic pressure/stroke volume and Elv = end-systolic pressure/end-systolic volume and indexed to body surface area. After the intervention, women augmented indexed and un-indexed Elv from 2.09 ± 0.61 to 2.52 ± 0.80 mmHg/ml, p 0.05). Women also reduced end-systolic pressure (from 91 ± 10 to 87 ± 10 mmHg), and both groups reduced central pulse wave velocity (from 6.0 ± 1.0 to 5.6 ± 0.6 m/s, p < 0.05). We conclude that after 8 weeks of aerobic training, only women reduced their coupling ratio due to an increase in Elv. This suggests that aerobic exercise training elicits sex-dependent changes in the coupling ratio in young, healthy individuals.

  12. Teaching Adult Rats Spinalized as Neonates to Walk Using Trunk Robotic Rehabilitation: Elements of Success, Failure, and Dependence.

    Science.gov (United States)

    Udoekwere, Ubong I; Oza, Chintan S; Giszter, Simon F

    2016-08-10

    Robot therapy promotes functional recovery after spinal cord injury (SCI) in animal and clinical studies. Trunk actions are important in adult rats spinalized as neonates (NTX rats) that walk autonomously. Quadrupedal robot rehabilitation was tested using an implanted orthosis at the pelvis. Trunk cortical reorganization follows such rehabilitation. Here, we test the functional outcomes of such training. Robot impedance control at the pelvis allowed hindlimb, trunk, and forelimb mechanical interactions. Rats gradually increased weight support. Rats showed significant improvement in hindlimb stepping ability, quadrupedal weight support, and all measures examined. Function in NTX rats both before and after training showed bimodal distributions, with "poor" and "high weight support" groupings. A total of 35% of rats initially classified as "poor" were able to increase their weight-supported step measures to a level considered "high weight support" after robot training, thus moving between weight support groups. Recovered function in these rats persisted on treadmill with the robot both actuated and nonactuated, but returned to pretraining levels if they were completely disconnected from the robot. Locomotor recovery in robot rehabilitation of NTX rats thus likely included context dependence and/or incorporation of models of robot mechanics that became essential parts of their learned strategy. Such learned dependence is likely a hurdle to autonomy to be overcome for many robot locomotor therapies. Notwithstanding these limitations, trunk-based quadrupedal robot rehabilitation helped the rats to visit mechanical states they would never have achieved alone, to learn novel coordinations, and to achieve major improvements in locomotor function. Neonatal spinal transected rats without any weight support can be taught weight support as adults by using robot rehabilitation at trunk. No adult control rats with neonatal spinal transections spontaneously achieve similar changes

  13. CHRONIC ALCOHOLISM ON THE SEMINAL VESICLE AND TESTIS WEIGHT OF ADULT RATS (Rattus norvegicus)

    OpenAIRE

    Martinez, F. E.; Martinez, M.; Cagnon, V. H. A.; Mello Junior, W.; Padovani, C. R.; Garcia, P. J.

    1997-01-01

    Effects of experimental chronic alcoholism on the accessory sexual glands weight and testes weight were studied. Male adult albino rats received only sugar cane brandy at 30 Gay Lussac (v/v), while the controls received tap water. After periods of 60, 120, 180 and 240 days, rats from each group were anesthetized, weighed and sacrificed. Alterations in mean daily solid food intake and liquid, mean daily weight gain, mean prostate weight, mean seminal vesicle and coagulating gland weights and t...

  14. TVP1022 and propargylamine protect neonatal rat ventricular myocytes against doxorubicin-induced and serum starvation-induced cardiotoxicity.

    Science.gov (United States)

    Kleiner, Yana; Bar-Am, Orit; Amit, Tamar; Berdichevski, Alexandra; Liani, Esti; Maor, Gila; Reiter, Irina; Youdim, Moussa B H; Binah, Ofer

    2008-09-01

    We recently reported that propargylamine derivatives such as rasagiline (Azilect) and its S-isomer TVP1022 are neuroprotective. The aim of this study was to test the hypothesis that the neuroprotective agents TVP1022 and propargylamine (the active moiety of propargylamine derivatives) are also cardioprotective. We specifically investigated the protective efficacy of TVP1022 and propargylamine in neonatal rat ventricular myocytes (NRVM) against apoptosis induced by the anthracycline chemotherapeutic agent doxorubicin and by serum starvation. We demonstrated that pretreatment of NRVM cultures with TVP1022 or propargylamine attenuated doxorubicin-induced and serum starvation-induced apoptosis, inhibited the increase in cleaved caspase 3 levels, and reversed the decline in Bcl-2/Bax ratio. These cytoprotective effects were shown to reside in the propargylamine moiety. Finally, we showed that TVP1022 neither caused proliferation of the human cancer cell lines HeLa and MDA-231 nor interfered with the anti-cancer efficacy of doxorubicin. These results suggest that TVP1022 should be considered as a novel cardioprotective agent against ischemic insults and against anthracycline cardiotoxicity and can be coadministered with doxorubicin in the treatment of human malignancies.

  15. Modeling CICR in rat ventricular myocytes: voltage clamp studies

    Directory of Open Access Journals (Sweden)

    Palade Philip T

    2010-11-01

    Full Text Available Abstract Background The past thirty-five years have seen an intense search for the molecular mechanisms underlying calcium-induced calcium-release (CICR in cardiac myocytes, with voltage clamp (VC studies being the leading tool employed. Several VC protocols including lowering of extracellular calcium to affect Ca2+ loading of the sarcoplasmic reticulum (SR, and administration of blockers caffeine and thapsigargin have been utilized to probe the phenomena surrounding SR Ca2+ release. Here, we develop a deterministic mathematical model of a rat ventricular myocyte under VC conditions, to better understand mechanisms underlying the response of an isolated cell to calcium perturbation. Motivation for the study was to pinpoint key control variables influencing CICR and examine the role of CICR in the context of a physiological control system regulating cytosolic Ca2+ concentration ([Ca2+]myo. Methods The cell model consists of an electrical-equivalent model for the cell membrane and a fluid-compartment model describing the flux of ionic species between the extracellular and several intracellular compartments (cell cytosol, SR and the dyadic coupling unit (DCU, in which resides the mechanistic basis of CICR. The DCU is described as a controller-actuator mechanism, internally stabilized by negative feedback control of the unit's two diametrically-opposed Ca2+ channels (trigger-channel and release-channel. It releases Ca2+ flux into the cyto-plasm and is in turn enclosed within a negative feedback loop involving the SERCA pump, regulating[Ca2+]myo. Results Our model reproduces measured VC data published by several laboratories, and generates graded Ca2+ release at high Ca2+ gain in a homeostatically-controlled environment where [Ca2+]myo is precisely regulated. We elucidate the importance of the DCU elements in this process, particularly the role of the ryanodine receptor in controlling SR Ca2+ release, its activation by trigger Ca2+, and its

  16. Failure of antiarrhythmic drugs to prevent experimental reperfusion ventricular fibrillation.

    Science.gov (United States)

    Naito, M; Michelson, E L; Kmetzo, J J; Kaplinsky, E; Dreifus, L S

    1981-01-01

    Ninety-nine adult mongrel dogs underwent acute ligation of the proximal left anterior descending coronary artery. Thirty minutes later, the occlusion was released to evaluate the effectiveness of five antiarrhythmic protocols in eliminating reperfusion ventricular fibrillation. The five protocols included: protocol 1 --i.v. lidocaine, preligation and prerelease (n = 19); protocol 2 -- i.v. lidocaine, prereperfusion only (n = 22); protocol 3 -- chronic, oral, daily amiodarone for 2 weeks preligation (n = 19); protocol 4 -- i.v. procainamide, preligation and prereperfusion (n = 21); and protocol 5 -- i.v. verapamil, prereperfusion (n = 18). Each regimen was evaluated with respect to the incidence of reperfusion ventricular fibrillation in dogs that survived to reperfusion, and the results were compared to 77 control dogs that underwent identical coronary artery occlusion and release procedures without drug therapy. The incidence of reperfusion ventricular fibrillation was as follows: protocol 1 -- seven of 15 dogs (47%); protocol 2 -- six of 18 (33%); protocol 3 -- 11 of 16 dogs (69%); protocol 4 -- eight of 17 dogs (47%); and protocol 5 -- 10 of 17 dogs (59%), compared with 36 of 60 (60%) in control dogs. Using chi-square analysis, protocol 2 was beneficial (p antecedent coronary artery ligation periods, and predictive risk indexes for the occurrence of reperfusion ventricular fibrillation were developed. the Mantel-Haenszel method of statistical analysis revealed that none of these protocols resulted in a statistically significant reduction in the incidence of reperfusion ventricular fibrillation. Thus, use of these predictive indexes plus appropriate statistical methods has revealed, unexpectedly, limitations in the efficacy of a spectrum of antiarrhythmic agents in preventing reperfusion ventricular fibrillation.

  17. In vitro reestablishment of cell-cell contacts in adult rat cardiomyocytes. Functional role of transmembrane components in the formation of new intercalated disk-like cell contacts.

    Science.gov (United States)

    Eppenberger, H M; Zuppinger, C

    1999-01-01

    Primary adult rat cardiomyocytes (ARC)in culture are shown to be a model system for cardiac cell hypertrophy in vitro. ARC undergo a process of morphological transformation and grow only by increase in cell size, however, without loss of the cardiac phenotype. The isolated cells spread and establish new cell-cell contacts, eventually forming a two-dimensional heart tissue-like synchronously beating cell sheet. The reformation of specific cell contacts (intercalated disks) is shown also between ventricular and atrial cardiomyocytes by using antibodies against the gap junction protein connexin-43 and after microinjection into ARC of N-cadherin cDNA fused to reporter green fluorescent protein (GFP) cDNA. The expressed fusion protein allowed the study of live cell cultures and of the dynamics of the adherens junction protein N-cadherin during the formation of new cell-cell contacts. The possible use of the formed ARC cell-sheet cells under microgravity conditions as a test system for the reformation of the cytoskeleton of heart muscle cells is proposed.

  18. 4-Guanidino-n-butyl syringate (Leonurine, SCM 198) protects H9c2 rat ventricular cells from hypoxia-induced apoptosis.

    Science.gov (United States)

    Liu, Xin-hua; Chen, Pei-fang; Pan, Li-long; Silva, Ranil De; Zhu, Yi-zhun

    2009-11-01

    In the present study, we examined the ability of a chemically synthesized compound based on the structure of leonurine, a phytochemical component of Herba leonuri, to protect H9c2 rat ventricular cells from apoptosis induced by hypoxia and serum deprivation, as a model of ischemia. The results revealed a concentration-dependent increase in cell viability associated with leonurine treatment, accompanied by a consistent decline in lactate dehydrogenase leakage into the culture medium. The fraction of annexin V-fluorescein isothiocyanate-positive cells was increased by hypoxia but reduced by leonurine. These changes were associated with increased expression of the antiapoptotic gene, Bcl-2, and reduced expression of the proapoptotic gene, Bax. Leonurine also reduced the cytosolic Ca overload induced by hypoxia. These results suggest that leonurine elicits potent cardioprotective effects in H9c2 cells, and these effects may be mediated by inhibition of intracellular Ca overload and apoptosis during hypoxia.

  19. Expression of developmental myosin and morphological characteristics in adult rat skeletal muscle following exercise-induced injury.

    Science.gov (United States)

    Smith, H K; Plyley, M J; Rodgers, C D; McKee, N H

    1999-07-01

    The extent and stability of the expression of developmental isoforms of myosin heavy chain (MHCd), and their association with cellular morphology, were determined in adult rat skeletal muscle fibres following injury induced by eccentrically-biased exercise. Adult female Wistar rats [274 (10) g] were either assigned as non-exercised controls or subjected to 30 min of treadmill exercise (grade, -16 degrees; speed, 15 m x min(-1)), and then sacrificed following 1, 2, 4, 7, or 12 days of recovery (n = 5-6 per group). Histologically and immunohistologically stained serial, transverse cryosections of the soleus (S), vastus intermedius (VI), and tibialis anterior (TA) muscles were examined using light microscopy and digital imaging. Fibres staining positively for MHCd (MHCd+) were seldom detected in the TA. In the VI and S, higher proportions of MHCd+ fibres (0.8% and 2.5%, respectively) were observed in rats at 4 and 7 days post-exercise, in comparison to all other groups combined (0.2%, 1.2%; P < or = 0.01). In S, MHCd+ fibres were observed less frequently by 12 days (0.7%) than at 7 days (2.6%) following exercise. The majority (85.1%) of the MHCd+ fibres had morphological characteristics indicative of either damage, degeneration, repair or regeneration. Most of the MHCd+ fibres also expressed adult slow, and/or fast myosin heavy chain. Quantitatively, the MHCd+ fibres were smaller (< 2500 microm2) and more angular than fibres not expressing MHCd. Thus, there was a transient increase in a small, but distinct population of MHCd+ fibres following unaccustomed, functional exercise in adult rat S and VI muscles. The observed close coupling of MHCd expression with morphological changes within muscle fibres suggests that these characteristics have a common, initial exercise-induced injury-related stimulus.

  20. Western High-Fat Diet Consumption during Adolescence Increases Susceptibility to Traumatic Stress while Selectively Disrupting Hippocampal and Ventricular Volumes

    Science.gov (United States)

    Kalyan-Masih, Priya; Vega-Torres, Julio David; Haddad, Elizabeth; Rainsbury, Sabrina; Baghchechi, Mohsen

    2016-01-01

    Abstract Psychological trauma and obesity co-occur frequently and have been identified as major risk factors for psychiatric disorders. Surprisingly, preclinical studies examining how obesity disrupts the ability of the brain to cope with psychological trauma are lacking. The objective of this study was to determine whether an obesogenic Western-like high-fat diet (WD) predisposes rats to post-traumatic stress responsivity. Adolescent Lewis rats (postnatal day 28) were fed ad libitum for 8 weeks with either the experimental WD diet (41.4% kcal from fat) or the control diet (16.5% kcal from fat). We modeled psychological trauma by exposing young adult rats to a cat odor threat. The elevated plus maze and the open field test revealed increased psychological trauma-induced anxiety-like behaviors in the rats that consumed the WD when compared with control animals 1 week after undergoing traumatic stress (p < 0.05). Magnetic resonance imaging showed significant hippocampal atrophy (20% reduction) and lateral ventricular enlargement (50% increase) in the animals fed the WD when compared with controls. These volumetric abnormalities were associated with behavioral indices of anxiety, increased leptin and FK506-binding protein 51 (FKBP51) levels, and reduced hippocampal blood vessel density. We found asymmetric structural vulnerabilities to the WD, particularly the ventral and left hippocampus and lateral ventricle. This study highlights how WD consumption during adolescence impacts key substrates implicated in post-traumatic stress disorder. Understanding how consumption of a WD affects the developmental trajectories of the stress neurocircuitry is critical, as stress susceptibility imposes a marked vulnerability to neuropsychiatric disorders. PMID:27844058

  1. Inhibition of acetylcholinesterase activity in brain and behavioral analysis in adult rats after chronic administration of fenproporex.

    Science.gov (United States)

    Rezin, Gislaine T; Scaini, Giselli; Ferreira, Gabriela K; Cardoso, Mariane R; Gonçalves, Cinara L; Constantino, Larissa S; Deroza, Pedro F; Ghedim, Fernando V; Valvassori, Samira S; Resende, Wilson R; Quevedo, João; Zugno, Alexandra I; Streck, Emilio L

    2012-12-01

    Fenproporex is an amphetamine-based anorectic and it is rapidly converted in vivo into amphetamine. It elevates the levels of extracellular dopamine in the brain. Acetylcholinesterase is a regulatory enzyme which is involved in cholinergic synapses and may indirectly modulate the release of dopamine. Thus, we investigated whether the effects of chronic administration of fenproporex in adult rats alters acquisition and retention of avoidance memory and acetylcholinesterase activity. Adult male Wistar rats received repeated (14 days) intraperitoneal injection of vehicle or fenproporex (6.25, 12.5 or 25 mg/kg i.p.). For behavioral assessment, animals were submitted to inhibitory avoidance (IA) tasks and continuous multiple trials step-down inhibitory avoidance (CMIA). Acetylcholinesterase activity was measured in the prefrontal cortex, hippocampus, hypothalamus and striatum. The administration of fenproporex (6.25, 12.5 and 25 mg/kg) did not induce impairment in short and long-term IA or CMIA retention memory in rats. In addition, longer periods of exposure to fenproporex administration decreased acetylcholinesterase activity in prefrontal cortex and striatum of rats, but no alteration was verified in the hippocampus and hypothalamus. In conclusion, the present study showed that chronic fenproporex administration decreased acetylcholinesterase activity in the rat brain. However, longer periods of exposure to fenproporex did not produce impairment in short and long-term IA or CMIA retention memory in rats.

  2. TVP1022 Protects Neonatal Rat Ventricular Myocytes against Doxorubicin-Induced Functional Derangements

    Science.gov (United States)

    Berdichevski, Alexandra; Meiry, Gideon; Milman, Felix; Reiter, Irena; Sedan, Oshra; Eliyahu, Sivan; Duffy, Heather S.; Youdim, Moussa B.; Binah, Ofer

    2010-01-01

    Our recent studies demonstrated that propargylamine derivatives such as rasagiline (Azilect, Food and Drug Administration-approved anti-Parkinson drug) and its S-isomer TVP1022 protect cardiac and neuronal cell cultures against apoptotic-inducing stimuli. Studies on structure-activity relationship revealed that their neuroprotective effect is associated with the propargylamine moiety, which protects mitochondrial viability and prevents apoptosis by activating Bcl-2 and protein kinase C-ε and by down-regulating the proapoptotic protein Bax. Based on the established cytoprotective and neuroprotective efficacies of propargylamine derivatives, as well as on our recent study showing that TVP1022 attenuates serum starvation-induced and doxorubicin-induced apoptosis in neonatal rat ventricular myocytes (NRVMs), we tested the hypothesis that TVP1022 will also provide protection against doxorubicin-induced NRVM functional derangements. The present study demonstrates that pretreatment of NRVMs with TVP1022 (1 μM, 24 h) prevented doxorubicin (0.5 μM, 24 h)-induced elevation of diastolic [Ca2+]i, the slowing of [Ca2+]i relaxation kinetics, and the decrease in the rates of myocyte contraction and relaxation. Furthermore, pretreatment with TVP1022 attenuated the doxorubicin-induced reduction in the protein expression of sarco/endoplasmic reticulum calcium (Ca2+) ATPase, Na+/Ca2+ exchanger 1, and total connexin 43. Finally, TVP1022 diminished the inhibitory effect of doxorubicin on gap junctional intercellular coupling (measured by means of Lucifer yellow transfer) and on conduction velocity, the amplitude of the activation phase, and the maximal rate of activation (dv/dtmax) measured by the Micro-Electrode-Array system. In summary, our results indicate that TVP1022 acts as a novel cardioprotective agent against anthracycline cardiotoxicity, and therefore potentially can be coadmhence, the inistered with doxorubicin in the treatment of malignancies in humans. PMID:19915070

  3. Release of atrial natriuretic peptide from rat myocardium in vitro: effect of minoxidil-induced hypertrophy.

    Science.gov (United States)

    Kinnunen, P.; Taskinen, T.; Leppäluoto, J.; Ruskoaho, H.

    1990-01-01

    1. Ventricular hypertrophy is characterized by stimulation of ventricular synthesis of atrial natriuretic peptide (ANP). To examine the role of ventricular ANP levels in the secretion of ANP into the circulation, atrial and ventricular levels of immunoreactive-ANP (IR-ANP) as well as ANP messenger RNA (mRNA), and the release of IR-ANP from isolated perfused hearts, both before and after atrialectomy, were measured simultaneously in control and minoxidil-treated Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. 2. IR-ANP levels in the ventricles of untreated, 12 month-old SHR with severe ventricular hypertrophy were increased when compared to age-matched WKY rats. Minoxidil treatment for 8 weeks in both strains resulted in a decrease in mean arterial pressure and increases in ventricular weight to body weight ratios, plasma IR-ANP concentrations (in WKY from 133 +/- 20 to 281 +/- 34 pg ml-1, P less than 0.01; in SHR from 184 +/- 38 to 339 +/- 61 pg ml-1, P less than 0.05), and in ventricular IR-ANP contents (in WKY: 53%; in SHR: 41%). A highly significant correlation was found between ventricular IR-ANP content and ventricular weight to body weight ratio (r = 0.59, P less than 0.001, n = 26). 3. When studied in vitro, in isolated perfused heart preparations, the hypertrophied ventricular tissue after atrialectomy secreted more ANP into the perfusate than ventricles of the control hearts; ventricles contributed 28%, 22%, 18% and 15% of the total ANP release to perfusate in the minoxidil-treated SHR, control SHR, minoxidil-treated WKY and control WKY, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2141796

  4. Time-dependent responses of rat troponin I and cardiac injury following isoproterenol administration

    Directory of Open Access Journals (Sweden)

    Sabaheta Hasić

    2011-02-01

    Full Text Available Aim To develop a rat model of myocardial infarction induced by isoproterenol (ISO. We investigated a type of histological myocardial changes and cardiac troponin I (TnI kinetic. Methods The study has used adult, male, Wistar strain rats. Rats were distributed in ISO and control groups. Rats treated with ISO were divided into groups according to the time of cTnI and myocardial lesion analyses: ISO I (30’, ISO II (60’, ISO III (120’ and ISO IV (240’. We determined cTnI (Life Diagnostics Inc. West Chester PA, USA in the serum by ELISA method. We performed histological analysis on the specimens of left ventricular wall stained by hematoxillin-eosin (HE method. Results The irst statistically signiicant rise of cTnI was noted 30 minutes after the ISO administration. There was no statistically signiicant difference between cTnI mean values among the ISO groups. Observed myocardial histological changes were time dependent. Conclusions This model can be suitable for cardioprotective and cardiotoxicity supstance investigations followed by cTnI measurement in blood. The similarity between induced myocardial lesion on animal model in our study and human myocardial lesion in ischemia give us suficient impulse for further preclinical researches of new cardiac markers.

  5. Developmental vitamin D deficiency alters MK 801-induced hyperlocomotion in the adult rat: An animal model of schizophrenia.

    Science.gov (United States)

    Kesby, James P; Burne, Thomas H J; McGrath, John J; Eyles, Darryl W

    2006-09-15

    Developmental vitamin D (DVD) deficiency has been proposed as a risk factor for schizophrenia. The behavioral phenotype of adult rats subjected to transient low prenatal vitamin D is characterized by spontaneous hyperlocomotion but normal prepulse inhibition of acoustic startle (PPI). The aim of this study was to examine the impact of selected psychotropic agents and one well-known antipsychotic agent on the behavioral phenotype of DVD deplete rats. Control versus DVD deplete adult rats were assessed on holeboard, open field and PPI. In the open field, animals were given MK-801 and/or haloperidol. For PPI, the animals were given apomorphine or MK-801. DVD deplete rats had increased baseline locomotion on the holeboard task and increased locomotion in response to MK-801 compared to control rats. At low doses, haloperidol antagonized the MK-801 hyperactivity of DVD deplete rats preferentially and, at a high dose, resulted in a more pronounced reduction in spontaneous locomotion in DVD deplete rats. DVD depletion did not affect either baseline or drug-mediated PPI response. These results suggest that DVD deficiency is associated with a persistent alteration in neuronal systems associated with motor function but not those associated with sensory motor gating. In light of the putative association between low prenatal vitamin D and schizophrenia, the discrete behavioral differences associated with the DVD model may help elucidate the neurobiological correlates of schizophrenia.

  6. Thyroxine binding to serum thyronine-binding globulin in thyroidectomized adult and normal neonatal rats

    International Nuclear Information System (INIS)

    Young, R.A.; Meyers, B.; Alex, S.; Fang, S.L.; Braverman, L.E.

    1988-01-01

    The amount of tracer [125I]T4 bound to serum thyronine-binding globulin (TBG) was measured by polyacrylamide gel electrophoresis in adult thyroidectomized (TX) rats and normal 1-day to 4-week-old rat puts. Thyroidectomy was associated with the appearance of significant amounts of [125I]T4 binding to serum TBG in lean rats, but not in obese Zucker rats. Treatment of the TX rats in vivo with replacement doses of T4 prevented this increase in TBG binding, but enrichment of serum from TX rats with T4 did not. Significant amounts of tracer [125I]T4 binding to TBG was present in serum from 1- to 3-week-old normal rat pups, but not in 1-day- or 4-week-old pups. There were significantly higher levels of TBG binding of [125I]T4 in serum from 2-week-old rat pups raised in litters of 16 pups compared to those raised in litters of 4 pups. All manipulations that result in the appearance of TBG in rat serum also result in either weight loss or a slowing in the rate of growth, suggesting that the appearance of TBG in rat serum has a nutritional component. This possibility is further supported by the observations that increases in TBG binding of [125I]T4 are not found in obese Zucker rats fed a low protein-high carbohydrate diet for 14 days or fasted for 7 days, or after thyroidectomy, perhaps owing to the large stores of fuel in the obese rat

  7. Applications of magnetic resonance imaging in the assessment of left ventricular dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Beacock, David John

    2002-07-01

    This thesis has described the use of Magnetic Resonance Imaging (MRI) in the investigation of left ventricular dimensions and systolic function. This has been performed in conditions of left ventricular dysfunction, in congestive cardiac failure and following anterior myocardial infarction. The reproducibility of measurements of left ventricular dimensions using MRI has been presented. Such measurements were shown to be reproducible between different MRI studies of normal volunteers and patients with congestive heart failure. Furthermore, measurements from different MRI studies obtained from two commercially different systems were reproducible for the same subject groups. Ventricular dimensions and systolic function was evaluated in adult normal volunteers of different ages. Although left ventricular volumes and mass remained unchanged, detailed studies of the systolic images revealed significant differences between the two age groups. Differences in left ventricular cavity volumes and mass between patients with congestive heart failure and age-matched normal volunteers were also investigated. Left ventricular volumes and myocardial mass were assessed in a group of patients following anterior myocardial infarction. End-systolic volume was significantly increased compared to age-matched volunteers, but no changes in end-diastolic volume or myocardial mass was observed. Serial re-evaluation of these patients revealed no other changes over the subsequent six months. All these patients were treated with optimal medical therapy (thrombolysis, aspirin, beta-blockade and angiotensin converting enzyme inhibition). Thus, the use of this therapy may attenuate the process of left ventricular remodelling. Regional wall thickness was measured in the post-infarct patients. Wall thickening was significantly reduced both in the infarcted regions and in myocardium remote to the infarction. In contrast to previous echocardiographic studies, no 'hypercontractility' was

  8. Low maternal care exacerbates adult stress susceptibility in the chronic mild stress rat model of depression

    DEFF Research Database (Denmark)

    Henningsen, Kim; Johannesen, Mads Dyrvig; Bouzinova, Elena

    2012-01-01

    In the present study we report the finding that the quality of maternal care, in early life, increased the susceptibility to stress exposure in adulthood, when rats were exposed to the chronic mild stress paradigm. Our results indicate that high, as opposed to low maternal care, predisposed rats...... to a differential stress-coping ability. Thus rats fostered by low maternal care dams became more prone to adopt a stress-susceptible phenotype developing an anhedonic-like condition. Moreover, low maternal care offspring had lower weight gain and lower locomotion, with no additive effect of stress. Subchronic...... exposure to chronic mild stress induced an increase in faecal corticosterone metabolites, which was only significant in rats from low maternal care dams. Examination of glucocorticoid receptor exon 17 promoter methylation in unchallenged adult, maternally characterized rats, showed an insignificant...

  9. Protein-Energy Malnutrition Causes Deficits in Motor Function in Adult Male Rats.

    Science.gov (United States)

    Alaverdashvili, Mariam; Li, Xue; Paterson, Phyllis G

    2015-11-01

    Adult protein-energy malnutrition (PEM) often occurs in combination with neurological disorders affecting hand use and walking ability. The independent effects of PEM on motor function are not well characterized and may be obscured by these comorbidities. Our goal was to undertake a comprehensive evaluation of sensorimotor function with the onset and progression of PEM in an adult male rat model. In Expt. 1 and Expt. 2, male Sprague-Dawley rats (14-15 wk old) were assigned ad libitum access for 4 wk to normal-protein (NP) or low-protein (LP) diets containing 12.5% and 0.5% protein, respectively. Expt. 1 assessed muscle strength, balance, and skilled walking ability on days 2, 8, and 27 by bar-holding, cylinder, and horizontal ladder walking tasks, respectively. In addition to food intake and body weight, nutritional status was determined on days 3, 9, and 28 by serum acute-phase reactant and corticosterone concentrations and liver lipids. Expt. 2 addressed the effect of an LP diet on hindlimb muscle size. PEM evolved over time in rats consuming the LP diet. Total food intake decreased by 24% compared with the NP group. On day 28, body weight and serum albumin decreased by 31% and 26%, respectively, and serum α2-macroglobulin increased by 445% (P malnutrition. This model can be used in combination with disease models of sensorimotor deficits to examine the interactions between nutritional status, other treatments, and disease progression. © 2015 American Society for Nutrition.

  10. Outcomes of ventricular assist device implantation in children and young adults: the Melbourne experience.

    Science.gov (United States)

    Shi, William Y; Marasco, Silvana F; Saxena, Pankaj; d'Udekem, Yves; Yong, Matthew S; Mitnovetski, Sergei; Brizard, Christian P; McGiffin, David C; Weintraub, Robert G; Konstantinov, Igor E

    2016-12-01

    We evaluated our experience with ventricular assist device (VAD) implantation in children and young adults. A total of 64 patients underwent VAD implantation in two centres. The mean age was 15 ± 7.2 years. Thirty-five (55%) patients were under 18 years of age. Devices implanted included the Thoratec Paracorporeal in 30 (47%) patients, Berlin Heart EXCOR in 11 (17%) and VentrAssist in 14 (22%). The diagnosis was cardiomyopathy in 53, congenital heart disease in 11, and graft failure in four patients. There were 10 (16%) in-hospital deaths. Mortality was higher in patients <18 years of age (26% compared with 3.4% for those ≥18 years, P = 0.02). The use of extracorporeal membrane oxygenation prior to VAD implantation was associated with higher mortality (P = 0.006). Seventeen (27%) patients experienced stroke. Nine patients (14%) required change of VAD because of thrombosis. Transplantation was performed in 44 patients after a mean of 131 ± 141 days on VAD, 11 patients died without transplantation and three patients currently await transplantation. The VAD was explanted in six patients because of recovery. Overall survival from VAD implantation was 69% and 61% at 5 and 10 years, respectively. The 5-year post-transplant survival for those bridged with VAD support was 91% and was comparable with a cohort of patients who did not receive a pre-transplant VAD. Children requiring pre-transplant VAD support have a higher mortality and morbidity compared with young adults. Survival after heart transplantation those supported with VADs was similar to patients of similar age who did not require pre-transplant support. © 2015 Royal Australasian College of Surgeons.

  11. Changes in calcium uptake rate by rat cardiac mitochondria during postnatal development.

    Science.gov (United States)

    Bassani, R A; Fagian, M M; Bassani, J W; Vercesi, A E

    1998-10-01

    Ca2+ uptake, transmembrane electrical potential (Deltapsim) and oxygen consumption were measured in isolated ventricular mitochondria of rats from 3 days to 5 months of age. Estimated values of ruthenium red-sensitive, succinate-supported maximal rate of Ca2+ uptake (Vmax, expressed as nmol Ca2+/min/mg protein) were higher in neonates and gradually fell during postnatal development (from 435+/-24 at 3-6 days, to 156+/-10 in adults,Palpha-ketoglutarate as substrates) and state 3ADP (alpha-ketoglutarate-supported) respiration rates, as well as Deltapsim values (approximately-150 mV). Respiration-independent Deltapsim and Ca2+ uptake, supported by valinomycin-induced K+ efflux were also investigated at these ages. A transient Deltapsim (approximately -30 mV) was evoked by valinomycin in both neonatal and adult mitochondria. Respiration-independent Ca2+ uptake was also transient, but its initial rate was significantly higher in neonates than in adults (49. 4+/-10.0v 28.0+/-5.7 mmol Ca2+/min/mg protein,P<0.01). These results indicate that Ca2+ uptake capacity of rat cardiac mitochondria is remarkably high just after birth and declines over the first weeks of postnatal life, without change in apparent affinity of the transporter. Increased mitochondrial Ca2+ uptake rate in neonates appears to be related to the uniporter itself, rather than to modification of the driving force of the transport. Copyright 1998 Academic Press

  12. Moxonidine-induced central sympathoinhibition improves prognosis in rats with hypertensive heart failure.

    Science.gov (United States)

    Honda, Nobuhiro; Hirooka, Yoshitaka; Ito, Koji; Matsukawa, Ryuichi; Shinohara, Keisuke; Kishi, Takuya; Yasukawa, Keiji; Utsumi, Hideo; Sunagawa, Kenji

    2013-11-01

    Enhanced central sympathetic outflow is an indicator of the prognosis of heart failure. Although the central sympatholytic drug moxonidine is an established therapeutic strategy for hypertension, its benefits for hypertensive heart failure are poorly understood. In the present study, we investigated the effects of central sympathoinhibition by intracerebral infusion of moxonidine on survival in a rat model of hypertensive heart failure and the possible mechanisms involved. As a model of hypertensive heart failure, we fed Dahl salt-sensitive rats an 8% NaCl diet from 7 weeks of age. Intracerebroventricular (ICV) infusion of moxonidine (moxonidine-ICV-treated group [Mox-ICV]) or vehicle (vehicle-ICV-treated group [Veh-ICV]) was performed at 14-20 weeks of age, during the increased heart failure phase. Survival rates were examined, and sympathetic activity, left ventricular function and remodelling, and brain oxidative stress were measured. Hypertension and left ventricular hypertrophy were established by 13 weeks of age. At around 20 weeks of age, Veh-ICV rats exhibited overt heart failure concomitant with increased urinary norepinephrine (uNE) excretion as an index of sympathetic activity, dilated left ventricle, decreased percentage fractional shortening, and myocardial fibrosis. Survival rates at 21 weeks of age (n = 28) were only 23% in Veh-ICV rats, and 76% (n = 17) in Mox-ICV rats with concomitant decreases in uNE, myocardial fibrosis, collagen type I/III ratio, brain oxidative stress, and suppressed left ventricular dysfunction. Moxonidine-induced central sympathoinhibition attenuated brain oxidative stress, prevented cardiac dysfunction and remodelling, and improved the prognosis in rats with hypertensive heart failure. Central sympathoinhibition can be effective for the treatment of hypertensive heart failure.

  13. Ultrafine Particulate Matter Combined With Ozone Exacerbates Lung Injury in Mature Adult Rats With Cardiovascular Disease.

    Science.gov (United States)

    Wong, Emily M; Walby, William F; Wilson, Dennis W; Tablin, Fern; Schelegle, Edward S

    2018-05-01

    Particulate matter (PM) and ozone (O3) are dominant air pollutants that contribute to development and exacerbation of multiple cardiopulmonary diseases. Mature adults with cardiovascular disease (CVD) are particularly susceptible to air pollution-related cardiopulmonary morbidities and mortalities. The aim was to investigate the biologic potency of ultrafine particulate matter (UFPM) combined with O3 in the lungs of mature adult normotensive and spontaneously hypertensive (SH) Wistar-Kyoto rats. Conscious, mature adult male normal Wistar-Kyoto (NW) and SH rats were exposed to one of the following atmospheres: filtered air (FA); UFPM (∼ 250 μg/m3); O3 (1.0 ppm); or UFPM + O3 (∼ 250 μg/m3 + 1.0 ppm) combined for 6 h, followed by an 8 h FA recovery period. Lung sections were evaluated for lesions in the large airways, terminal bronchiolar/alveolar duct regions, alveolar parenchyma, and vasculature. NW and SH rats were similarly affected by the combined-pollutant exposure, displaying severe injury in both large and small airways. SH rats were particularly susceptible to O3 exposure, exhibiting increased injury scores in terminal bronchioles and epithelial degeneration in large airways. UFPM-exposure groups had minimal histologic changes. The chemical composition of UFPM was altered by the addition of O3, indicating that ozonolysis promoted compound degradation. O3 increased the biologic potency of UFPM, resulting in greater lung injury following exposure. Pathologic manifestations of CVD may confer susceptibility to air pollution by impairing normal lung defenses and responses to exposure.

  14. Dyssynchronous Ventricular Activation in Asymptomatic Wolff-Parkinson-White Syndrome: A Risk Factor for Development of Dilated Cardiomyopathy

    Science.gov (United States)

    Udink ten Cate, Floris EA; Wiesner, Nathalie; Trieschmann, Uwe; Khalil, Markus; Sreeram, Narayanswami

    2010-01-01

    A subset of children and adults with Wolff-Parkinson-White (WPW) syndrome develop dilated cardiomyopathy (DCM). Although DCM may occur in symptomatic WPW patients with sustained tachyarrhythmias, emerging evidence suggests that significant left ventricular dysfunction may arise in WPW in the absence of incessant tachyarrhythmias. An invariable electrophysiological feature in this non-tachyarrhythmia type of DCM is the presence of a right-sided septal or paraseptal accessory pathway. It is thought that premature ventricular activation over these accessory pathways induces septal wall motion abnormalities and ventricular dyssynchrony. LV dyssynchrony induces cellular and structural ventricular remodelling, which may have detrimental effects on cardiac performance. This review summarizes recent evidence for development of DCM in asymptomatic patients with WPW, discusses its pathogenesis, clinical presentation, management and treatment. The prognosis of accessory pathway-induced DCM is excellent. LV dysfunction reverses following catheter ablation of the accessory pathway, suggesting an association between DCM and ventricular preexcitation. Accessory pathway-induced DCM should be suspected in all patients presenting with heart failure and overt ventricular preexcitation, in whom no cause for their DCM can be found. PMID:20552060

  15. Relationship between Fibrosis and Ventricular Arrhythmias in Chagas Heart Disease Without Ventricular Dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Tassi, Eduardo Marinho, E-mail: etassi@ibest.com.br [Instituto de Cardiologia Edson Saad - Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ (Brazil); Continentino, Marcelo Abramoff [Hospital Frei Galvão, Guaratinguetá, SP (Brazil); Nascimento, Emília Matos do; Pereira, Basílio de Bragança [Instituto de Cardiologia Edson Saad - Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ (Brazil); Coppe - Instituto Alberto Luiz Coimbra de Pós-Graduação e Pesquisa de Engenharia - UFRJ, Rio de Janeiro, RJ (Brazil); Pedrosa, Roberto Coury [Instituto de Cardiologia Edson Saad - Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ (Brazil)

    2014-05-15

    Patients with Chagas disease and segmental wall motion abnormality (SWMA) have worse prognosis independent of left ventricular ejection fraction (LVEF). Cardiac magnetic resonance (CMR) is currently the best method to detect SWMA and to assess fibrosis. To quantify fibrosis by using late gadolinium enhancement CMR in patients with Chagas disease and preserved or minimally impaired ventricular function (> 45%), and to detect patterns of dependence between fibrosis, SWMA and LVEF in the presence of ventricular arrhythmia. Electrocardiogram, treadmill exercise test, Holter and CMR were carried out in 61 patients, who were divided into three groups as follows: (1) normal electrocardiogram and CMR without SWMA; (2) abnormal electrocardiogram and CMR without SWMA; (3) CMR with SWMA independently of electrocardiogram. The number of patients with ventricular arrhythmia in relation to the total of patients, the percentage of fibrosis, and the LVEF were, respectively: Group 1, 4/26, 0.74% and 74.34%; Group 2, 4/16, 3.96% and 68.5%; and Group 3, 11/19, 14.07% and 55.59%. Ventricular arrhythmia was found in 31.1% of the patients. Those with and without ventricular arrhythmia had mean LVEF of 59.87% and 70.18%, respectively, and fibrosis percentage of 11.03% and 3.01%, respectively. Of the variables SWMA, groups, age, LVEF and fibrosis, only the latter was significant for the presence of ventricular arrhythmia, with a cutoff point of 11.78% for fibrosis mass (p < 0.001). Even in patients with Chagas disease and preserved or minimally impaired ventricular function, electrical instability can be present. Regarding the presence of ventricular arrhythmia, fibrosis is the most important variable, its amount being proportional to the complexity of the groups.

  16. Relationship between Fibrosis and Ventricular Arrhythmias in Chagas Heart Disease Without Ventricular Dysfunction

    International Nuclear Information System (INIS)

    Tassi, Eduardo Marinho; Continentino, Marcelo Abramoff; Nascimento, Emília Matos do; Pereira, Basílio de Bragança; Pedrosa, Roberto Coury

    2014-01-01

    Patients with Chagas disease and segmental wall motion abnormality (SWMA) have worse prognosis independent of left ventricular ejection fraction (LVEF). Cardiac magnetic resonance (CMR) is currently the best method to detect SWMA and to assess fibrosis. To quantify fibrosis by using late gadolinium enhancement CMR in patients with Chagas disease and preserved or minimally impaired ventricular function (> 45%), and to detect patterns of dependence between fibrosis, SWMA and LVEF in the presence of ventricular arrhythmia. Electrocardiogram, treadmill exercise test, Holter and CMR were carried out in 61 patients, who were divided into three groups as follows: (1) normal electrocardiogram and CMR without SWMA; (2) abnormal electrocardiogram and CMR without SWMA; (3) CMR with SWMA independently of electrocardiogram. The number of patients with ventricular arrhythmia in relation to the total of patients, the percentage of fibrosis, and the LVEF were, respectively: Group 1, 4/26, 0.74% and 74.34%; Group 2, 4/16, 3.96% and 68.5%; and Group 3, 11/19, 14.07% and 55.59%. Ventricular arrhythmia was found in 31.1% of the patients. Those with and without ventricular arrhythmia had mean LVEF of 59.87% and 70.18%, respectively, and fibrosis percentage of 11.03% and 3.01%, respectively. Of the variables SWMA, groups, age, LVEF and fibrosis, only the latter was significant for the presence of ventricular arrhythmia, with a cutoff point of 11.78% for fibrosis mass (p < 0.001). Even in patients with Chagas disease and preserved or minimally impaired ventricular function, electrical instability can be present. Regarding the presence of ventricular arrhythmia, fibrosis is the most important variable, its amount being proportional to the complexity of the groups

  17. Effects of thiamine deficiency on food intake and body weight increment in adult female and growing rats.

    Science.gov (United States)

    Bâ, Abdoulaye

    2012-09-01

    The present study compared the effects of thiamine (vitamin B1) deficiency (TD) on the patterns of food intake and body weight in adult female and neonatal Wistar rats. The adults weighed 250-270 g at the start and were fed for 60 days either with a synthetic TD diet (211 B1) or with the same synthetic diet+thiamine (210 B1). TD led to a marked reduction in food intake and the body weight set point, both recovering rapidly to their initial level in only 3 days after dietetic reversion. The effects of TD in developing rats were evaluated by subjecting pregnant rats to thiamine restriction during different time windows: prenatal (3 days before mating to parturition); perinatal (7 days after mating to the 10th postnatal day); and postnatal (from parturition to weaning). The effect of TD on the occurrence of low birth weight and ponderal growth retardation was examined from postnatal days 1 to 45. Only perinatal TD significantly decreased birth weight relative to untreated or pair-fed controls. Moreover, compared with the control treatments, ponderal growth retardation was not induced by prenatal TD, whereas induction of TD from perinatal into postnatal periods did cause ponderal growth retardation, with long-lasting effects persisting in adulthood. The results suggest a major physiological role of thiamine in the homeostasis of body weight programming, increment, and set point regulation in both offspring and adult female rats.

  18. Peripubertal castration of male rats, adult open field ambulation and partner preference behavior.

    Science.gov (United States)

    Brand, T; Slob, A K

    1988-09-15

    The validity of the hypothesis put forward earlier, that testicular secretions during puberty have an organizing effect on open field ambulation was examined. Male rats were castrated or sham-operated at days 21, 43 or 70. At the age of 17 weeks the males were tested in an automated, octagonal open field (3 consecutive days, 3 min/day) for locomotor activity. Male rats castrated at day 21 or day 43 ambulated more than sham-castrated controls. Males castrated at day 70 did not differ from sham-castrated controls. It thus appears that pubertal testicular secretion(s) organize adult open field locomotor activity in male rats. From 18 weeks of age partner preference behavior was tested in the same open field apparatus with one adjacent cage containing an ovariectomized female and an opposite one containing an ovariectomized female brought into heat. The females in the adjacent cages were separated from the experimental males in the octagonal cage by wire mesh. Peripubertally castrated males did not show a clear-cut partner preference, whereas the intact males preferred the vicinity of the estrous female. There were no differences among the males castrated either before, during or after puberty. Testosterone treatment (crystalline T in silastic capsules) caused peripubertally castrated males to prefer the estrous female. Thus, adult partner preference behavior does not seem to be organized by peripubertal testicular androgens.

  19. Neonatal programming with testosterone propionate reduces dopamine transporter expression in nucleus accumbens and methylphenidate-induced locomotor activity in adult female rats.

    Science.gov (United States)

    Dib, Tatiana; Martínez-Pinto, Jonathan; Reyes-Parada, Miguel; Torres, Gonzalo E; Sotomayor-Zárate, Ramón

    2018-07-02

    Research in programming is focused on the study of stimuli that alters sensitive periods in development, such as prenatal and neonatal stages, that can produce long-term deleterious effects. These effects can occur in various organs or tissues such as the brain, affecting brain circuits and related behaviors. Our laboratory has demonstrated that neonatal programming with sex hormones affects the mesocorticolimbic circuitry, increasing the synthesis and release of dopamine (DA) in striatum and nucleus accumbens (NAcc). However, the behavioral response to psychostimulant drugs such as methylphenidate and the possible mechanism(s) involved have not been studied in adult rats exposed to sex hormones during the first hours of life. Thus, the aim of this study was to examine the locomotor activity induced by methylphenidate (5mg/kg i.p.) and the expression of the DA transporter (DAT) in NAcc of adult rats exposed to a single dose of testosterone propionate (TP: 1mg/50μLs.c.) or estradiol valerate (EV: 0.1mg/50μLs.c.) at postnatal day 1. Our results demonstrated that adult female rats treated with TP have a lower methylphenidate-induced locomotor activity compared to control and EV-treated adult female rats. This reduction in locomotor activity is related with a lower NAcc DAT expression. However, neither methylphenidate-induced locomotor activity nor NAcc DAT expression was affected in EV or TP-treated adult male rats. Our results suggest that early exposure to sex hormones affects long-term dopaminergic brain areas involved in the response to psychostimulants, which could be a vulnerability factor to favor the escalating doses of drugs of abuse. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Study of the effects of a prenatal or postnatal irradiation of 150 rads in adult rats

    International Nuclear Information System (INIS)

    Coffigny, H.; Pasquier, C.

    Pregnant females and newborn rats were exposed to a gamma irradiation of 150 rads. The stage of gestation at the time of irradiation varied from 14 to 21 days. The newborn rats were irradiated at 0, 1 and 2 days of age. The effect of irradiation of foetus and newborn rats depends on the age of the animal at the time of irradiation. This effect was specially important at the beginning of the foetal life. Neonatal mortality, growth of body weight and adult brain development were investigated. A modification of germ cell radiosensitivity during the period studied, was emphasized [fr

  1. Adult and newborn rat inner retinal oxygenation during carbogen and 100% oxygen breathing. Comparison using magnetic resonance imaging delta Po2 mapping.

    Science.gov (United States)

    Berkowitz, B A

    1996-09-01

    To test the hypothesis that breathing carbogen (95% O2-5% CO2) oxygenates the inner retina better than breathing 100% oxygen using an magnetic resonance imaging (MRI) method that noninvasively measures inner retinal oxygenation in normal adult and newborn rats. Urethane-anesthetized adult and newborn (day 18) rats were studied. Sequential images were acquired in room air combined with either 100% oxygen or carbogen breathing. Normalized vitreous signal intensity changes were converted to oxygen tension changes (delta PO2) either on a pixel-by-pixel basis or in specific regions of interest. Systemic levels of hyperoxia during carbogen or 100% oxygen breathing were not significantly different (P > 0.05). In the adult rat, a significant difference (P = 0.017) was found in the preretinal vitreous delta PO2 during the breathing of either carbogen (130 +/- 9 mm Hg, mean +/- SEM; n = 5) or 100% oxygen (88 +/- 16 mm Hg; n = 5). Agreement was found between the MRI-determined delta PO2 values and literature oxygen microelectrodes data. In the newborn rat, significant differences (P delta PO2 were found during carbogen (164 +/- 23 mm Hg; n = 3) and oxygen breathing (91 +/- 8 mm Hg; n = 3). MRI delta PO2 mapping demonstrated for the first time that in the normal adult and newborn rat eye, carbogen breathing oxygenates the inner retina better than 100% oxygen breathing.

  2. Cardiopulmonary Changes with Moderate Decompression in Rats

    Science.gov (United States)

    Robinson, R.; Little, T.; Doursout, M.-F.; Butler, B. D.; Chelly, J. E.

    1996-01-01

    Sprague-Dawley rats were compressed to 616 kPa for 120 min then decompressed at 38 kPa/min to assess the cardiovascular and pulmonary responses to moderate decompression stress. In one series of experiments the rats were chronically instrumented with Doppler ultrasonic probes for simultaneous measurement of blood pressure, cardiac output, heart rate, left and right ventricular wall thickening fraction, and venous bubble detection. Data were collected at base-line, throughout the compression/decompression protocol, and for 120 min post decompression. In a second series of experiments the pulmonary responses to the decompression protocol were evaluated in non-instrumented rats. Analyses included blood gases, pleural and bronchoalveolar lavage (BAL) protein and hemoglobin concentration, pulmonary edema, BAL and lung tissue phospholipids, lung compliance, and cell counts. Venous bubbles were directly observed in 90% of the rats where immediate post-decompression autopsy was performed and in 37% using implanted Doppler monitors. Cardiac output, stroke volume, and right ventricular wall thickening fractions were significantly decreased post decompression, whereas systemic vascular resistance was increased suggesting a decrease in venous return. BAL Hb and total protein levels were increased 0 and 60 min post decompression, pleural and plasma levels were unchanged. BAL white blood cells and neutrophil percentages were increased 0 and 60 min post decompression and pulmonary edema was detected. Venous bubbles produced with moderate decompression profiles give detectable cardiovascular and pulmonary responses in the rat.

  3. Mild Thyroid Hormone Insufficiency During Development Compromises Activity-Dependent Neuroplasticity in the Hippocampus of Adult Male Rats

    Data.gov (United States)

    U.S. Environmental Protection Agency — behavioral measures of learning and memory in adult offspring of rats treated with thyroid hormone synthesis inhibitor, propylthiouracil. Electrophysiological...

  4. Comparative Effects of Oral Chlorpyrifos Exposure on Cholinesterase Activity and Muscarinic Receptor Binding in Neonatal and Adult Rat Heart

    Science.gov (United States)

    Howard, Marcia D.; Mirajkar, Nikita; Karanth, Subramanya; Pope, Carey N.

    2010-01-01

    Organophosphorus (OP) pesticides elicit acute toxicity by inhibiting acetylcholinesterase (AChE), the enzyme responsible for inactivating acetylcholine (ACh) at cholinergic synapses. A number of OP toxicants have also been reported to interact directly with muscarinic receptors, in particular the M2 muscarinic subtype. Parasympathetic innervation to the heart primarily regulates cardiac function by activating M2 receptors in the sinus node, atrial-ventricular node and conducting tissues. Thus, OP insecticides can potentially influence cardiac function in a receptor–mediated manner indirectly by inhibiting acetylcholinesterase and directly by binding to muscarinic M2 receptors. Young animals are generally more sensitive than adults to the acute toxicity of OP insecticides and age related differences in potency of direct binding to muscarinic receptors by some OP toxicants have been reported. We thus compared the effects of the common OP insecticide chlorpyrifos (CPF) on functional signs of toxicity and cardiac ChE activity and muscarinic receptor binding in neonatal and adult rats. Dosages were based on acute lethality (i.e., 0.5 and 1 × LD10: neonates, 7.5 and 15 mg/kg; adults, 68 and 136 mg/kg). Dose- and time-related changes in body weight and cholinergic signs of toxicity (involuntary movements) were noted in both age groups. With 1 × LD10, relatively similar maximal reductions in ChE activity (95%) and muscarinic receptor binding (≈ 30%) were noted, but receptor binding reductions appeared earlier in adults and were more prolonged in neonates. In vitro inhibition studies indicated that ChE in neonatal tissues was markedly more sensitive to inhibition by the active metabolite of chlorpyrifos (i.e., chlorpyrifos oxon, CPO) than enzyme in adult tissues (IC50 values: neonates, 17 nM; adults, 200 nM). Chelation of free calcium with EDTA had relatively little effect on in vitro cholinesterase inhibition, suggesting that differential A-esterase activity was not

  5. Effects of chronic isoproterenol administration of β1-adrenoceptors and growth of pancreas of young and adult rats

    International Nuclear Information System (INIS)

    Schneyer, C.A.; Humphreys-Beher, M.

    1988-01-01

    [ 3 H]Dihydroalprenolol (DHA) binding of membranes of adult pancreas differed from that of pancreas of young rats, and the DHA binding in the presence of atenolol or butoxamine also was different in the two age groups. The adult pancreas had 93% β 2 - and 7% β 1 -adrenoceptors and did not exhibit an increased incorporation of [ 3 H]thymidine into deoxyribonucleic acid (DNA) following 2 days of DL-isoproterenol (ISO) administration; in contrast, pancreas of the 20-day-old rat had 71% β 2 -adrenoceptors and 27% β 1 -adrenoceptors and exhibited a 34-fold increase over that of adult, and a 6-fold increase over that of the control 20-day-old pancreas. Acinar cell differentiation was also accelerated by a 7-day regimen of ISO administration from 13 to 20 days of age. These growth responses to ISO appear to be β 1 mediated. The lack of β 1 -adrenoceptors in the adult may account for the failure of the adult pancreas to exhibit a growth response to ISO

  6. Growth hormone-releasing hormone promotes survival of cardiac myocytes in vitro and protects against ischaemia-reperfusion injury in rat heart.

    Science.gov (United States)

    Granata, Riccarda; Trovato, Letizia; Gallo, Maria Pia; Destefanis, Silvia; Settanni, Fabio; Scarlatti, Francesca; Brero, Alessia; Ramella, Roberta; Volante, Marco; Isgaard, Jorgen; Levi, Renzo; Papotti, Mauro; Alloatti, Giuseppe; Ghigo, Ezio

    2009-07-15

    The hypothalamic neuropeptide growth hormone-releasing hormone (GHRH) stimulates GH synthesis and release in the pituitary. GHRH also exerts proliferative effects in extrapituitary cells, whereas GHRH antagonists have been shown to suppress cancer cell proliferation. We investigated GHRH effects on cardiac myocyte cell survival and the underlying signalling mechanisms. Reverse transcriptase-polymerase chain reaction analysis showed GHRH receptor (GHRH-R) mRNA in adult rat ventricular myocytes (ARVMs) and in rat heart H9c2 cells. In ARVMs, GHRH prevented cell death and caspase-3 activation induced by serum starvation and by the beta-adrenergic receptor agonist isoproterenol. The GHRH-R antagonist JV-1-36 abolished GHRH survival action under both experimental conditions. GHRH-induced cardiac cell protection required extracellular signal-regulated kinase (ERK)1/2 and phosphoinositide-3 kinase (PI3K)/Akt activation and adenylyl cyclase/cAMP/protein kinase A signalling. Isoproterenol strongly upregulated the mRNA and protein of the pro-apoptotic inducible cAMP early repressor, whereas GHRH completely blocked this effect. Similar to ARVMs, in H9c2 cardiac cells, GHRH inhibited serum starvation- and isoproterenol-induced cell death and apoptosis through the same signalling pathways. Finally, GHRH improved left ventricular recovery during reperfusion and reduced infarct size in Langendorff-perfused rat hearts, subjected to ischaemia-reperfusion (I/R) injury. These effects involved PI3K/Akt signalling and were inhibited by JV-1-36. Our findings suggest that GHRH promotes cardiac myocyte survival through multiple signalling mechanisms and protects against I/R injury in isolated rat heart, indicating a novel cardioprotective role of this hormone.

  7. Cardiac Resynchronization Therapy Defibrillator Treatment in a Child with Heart Failure and Ventricular Arrhythmia

    Directory of Open Access Journals (Sweden)

    Hak Ju Kim

    2016-08-01

    Full Text Available Cardiac resynchronization therapy (CRT is a new treatment for refractory heart failure. However, most patients with heart failure treated with CRT are adults, middle-aged or older with idiopathic or ischemic dilated cardiomyopathy. We treated a 12-year-old boy, who was transferred after cardiac arrest, with dilated cardiomyopathy, left bundle-branch block, and ventricular tachycardia. We performed cardiac resynchronization therapy with a defibrillator (CRT-D. After CRT-D, left ventricular ejection fraction improved from 22% to 4 4% a ssessed by e chocardiog ram 1 year p ostoperatively. On e lectrocardiog ram, Q RS d uration was shortened from 206 to 144 ms. The patient’s clinical symptoms also improved. For pediatric patients with refractory heart failure and ventricular arrhythmia, CRT-D could be indicated as an effective therapeutic option.

  8. Amiodarone for the treatment and prevention of ventricular fibrillation and ventricular tachycardia

    Directory of Open Access Journals (Sweden)

    Hugo Van Herendael

    2010-06-01

    Full Text Available Hugo Van Herendael, Paul DorianDivision of Cardiology, St. Michael’s Hospital, University of Toronto, Toronto, CanadaAbstract: Amiodarone has emerged as the leading antiarrhythmic therapy for termination and prevention of ventricular arrhythmia in different clinical settings because of its proven efficacy and safety. In patients with shock refractory out-of-hospital cardiac arrest and hemodynamically destabilizing ventricular arrhythmia, amiodarone is the most effective drug available to assist in resuscitation. Although the superiority of the transvenous implantable cardioverter defibrillator (ICD over amiodarone has been well established in the preventive treatment of patients at high risk of life-threatening ventricular arrhythmias, amiodarone (if used with a beta-blocker is the most effective antiarrhythmic drug to prevent ICD shocks and treat electrical storm. Both the pharmacokinetics and the electrophysiologic profile of amiodarone are complex, and its optimal and safe use requires careful patient surveillance with respect to potential adverse effects.Keywords: amiodarone, ventricular fibrillation, unstable ventricular tachycardia

  9. A procedure for culturing rat neocortex explants in a serum-free nutrient medium

    NARCIS (Netherlands)

    Romijn, H. J.; de Jong, B. M.; Ruijter, J. M.

    1988-01-01

    A procedure is described for long-term culturing of rat neocortex explants in a serum-free growth medium. Slices spanning the entire cortical depth from pial to ventricular side are prepared from 6-day-old rat pups. After preincubation in Hanks' balanced salt solution with extra glucose, the

  10. The overloaded right heart and ventricular interdependence.

    Science.gov (United States)

    Naeije, Robert; Badagliacca, Roberto

    2017-10-01

    The right and the left ventricle are interdependent as both structures are nested within the pericardium, have the septum in common and are encircled with common myocardial fibres. Therefore, right ventricular volume or pressure overloading affects left ventricular function, and this in turn may affect the right ventricle. In normal subjects at rest, right ventricular function has negligible interaction with left ventricular function. However, the right ventricle contributes significantly to the normal cardiac output response to exercise. In patients with right ventricular volume overload without pulmonary hypertension, left ventricular diastolic compliance is decreased and ejection fraction depressed but without intrinsic alteration in contractility. In patients with right ventricular pressure overload, left ventricular compliance is decreased with initial preservation of left ventricular ejection fraction, but with eventual left ventricular atrophic remodelling and altered systolic function. Breathing affects ventricular interdependence, in healthy subjects during exercise and in patients with lung diseases and altered respiratory system mechanics. Inspiration increases right ventricular volumes and decreases left ventricular volumes. Expiration decreases both right and left ventricular volumes. The presence of an intact pericardium enhances ventricular diastolic interdependence but has negligible effect on ventricular systolic interdependence. On the other hand, systolic interdependence is enhanced by a stiff right ventricular free wall, and decreased by a stiff septum. Recent imaging studies have shown that both diastolic and systolic ventricular interactions are negatively affected by right ventricular regional inhomogeneity and prolongation of contraction, which occur along with an increase in pulmonary artery pressure. The clinical relevance of these observations is being explored. Published on behalf of the European Society of Cardiology. All rights

  11. Neonatal stress tempers vulnerability of acute stress response in adult socially isolated rats

    Directory of Open Access Journals (Sweden)

    Mariangela Serra

    2014-06-01

    Full Text Available Adverse experiences occurred in early life and especially during childhood and adolescence can have negative impact on behavior later in life and the quality of maternal care is considered a critical moment that can considerably influence the development and the stress responsiveness in offspring. This review will assess how the association between neonatal and adolescence stressful experiences such as maternal separation and social isolation, at weaning, may influence the stress responsiveness and brain plasticity in adult rats. Three hours of separation from the pups (3-14 postnatal days significantly increased frequencies of maternal arched-back nursing and licking-grooming by dams across the first 14 days postpartum and induced a long-lasting increase in their blood levels of corticosterone. Maternal separation, which per sedid not modified brain and plasma allopregnanolone and corticosterone levels in adult rats, significantly reduced social isolation-induced decrease of the levels of these hormones. Moreover, the enhancement of corticosterone and allopregnanolone levels induced by foot shock stress in socially isolated animals that were exposed to maternal separation was markedly reduced respect to that observed in socially isolated animals. Our results suggest that in rats a daily brief separation from the mother during the first weeks of life, which per se did not substantially alter adult function and reactivity of hypothalamic-pituitary-adrenal (HPA axis, elicited a significant protection versus the subsequent long-term stressful experience such that induced by social isolation from weaning. Proceedings of the 10th International Workshop on Neonatology · Cagliari (Italy · October 22nd-25th, 2014 · The last ten years, the next ten years in NeonatologyGuest Editors: Vassilios Fanos, Michele Mussap, Gavino Faa, Apostolos Papageorgiou

  12. Surgery for ventricular tachycardia in patients undergoing surgical ventricular restoration: the Karolinska approach.

    Science.gov (United States)

    Sartipy, Ulrik; Albåge, Anders; Insulander, Per; Lindblom, Dan

    2007-09-01

    This article presents a review on the efficacy of surgical ventricular restoration and direct surgery for ventricular tachycardia in patients with left ventricular aneurysm or dilated ischemic cardiomyopathy. The procedure includes a non-electrophysiologically guided subtotal endocardiectomy and cryoablation in addition to endoventricular patch plasty of the left ventricle. Coronary artery bypass surgery and mitral valve repair are performed concomitantly as needed. In our experience, this procedure yielded a 90% success rate in terms of freedom from spontaneous ventricular tachycardia, with an early mortality rate of 3.8%. A practical guide to the pre- and postoperative management of these patients is provided.

  13. Decreased creatine kinase is linked to diastolic dysfunction in rats with right heart failure induced by pulmonary artery hypertension

    NARCIS (Netherlands)

    Fowler, Ewan D.; Benoist, David; Drinkhill, Mark J.; Stones, Rachel; Helmes, Michiel; Wüst, Rob C. I.; Stienen, Ger J. M.; Steele, Derek S.; White, Ed

    2015-01-01

    Our objective was to investigate the role of creatine kinase in the contractile dysfunction of right ventricular failure caused by pulmonary artery hypertension. Pulmonary artery hypertension and right ventricular failure were induced in rats by monocrotaline and compared to saline-injected control

  14. Thymoquinone supplementation ameliorates lead-induced testis function impairment in adult rats.

    Science.gov (United States)

    Mabrouk, Aymen; Ben Cheikh, Hassen

    2016-06-01

    This study was realized to investigate the possible beneficial effect of thymoquinone (TQ), the major active component of volatile oil of Nigella sativa seeds, against lead (Pb)-induced inhibition of rat testicular functions. Adult rats were randomized into four groups: a control group receiving no treatment; a Pb group exposed to 2000 parts per million (ppm) of Pb acetate in drinking water; a Pb-TQ group co-treated with Pb (as in Pb group) plus TQ (5 mg/kg body weight (b.w.)/day, per orally (p.o.)); and a TQ group receiving TQ (5 mg/kg b.w./day, p.o.). All treatments were for 5 weeks. No significant differences were observed for the body weight gain or for relative testes weight among the four groups of animals. Testicular Pb content significantly increased in metal-intoxicated rats compared with that in control rats. TQ supplementation had no effect on this testicular Pb accumulation. Interestingly, when coadministrated with Pb, TQ significantly improved the low plasma testosterone level and the decreased epididymal sperm count caused by Pb. In conclusion, the results suggest, for the first time, that TQ protects against Pb-induced impairment of testicular steroidogenic and spermatogenic functions. This study will open new perspectives for the clinical use of TQ in Pb intoxication. © The Author(s) 2014.

  15. The impact of adult vitamin D deficiency on behaviour and brain function in male Sprague-Dawley rats.

    Directory of Open Access Journals (Sweden)

    Jacqueline H Byrne

    Full Text Available BACKGROUND: Vitamin D deficiency is common in the adult population, and this has been linked to depression and cognitive outcomes in clinical populations. The aim of this study was to investigate the effects of adult vitamin D (AVD deficiency on behavioural tasks of relevance to neuropsychiatric disorders in male Sprague-Dawley rats. METHODS: Ten-week old male Sprague-Dawley rats were fed a control or vitamin D deficient diet for 6 weeks prior to, and during behavioural testing. We first examined a range of behavioural domains including locomotion, exploration, anxiety, social behaviour, learned helplessness, sensorimotor gating, and nociception. We then assessed locomotor response to the psychomimetic drugs, amphetamine and MK-801. Attention and vigilance were assessed using the 5 choice serial reaction time task (5C-SRT and the 5 choice continuous performance task (5C-CPT and, in a separate cohort, working memory was assessed using the delay match to sample (DMTS task. We also examined excitatory and inhibitory neurotransmitters in prefrontal cortex and striatum. RESULTS: AVD-deficient rats were deficient in vitamin D3 (<10 nM and had normal calcium and phosphate levels after 8-10 weeks on the diet. Overall, AVD deficiency was not associated with an altered phenotype across the range of behavioural domains tested. On the 5C-SRT AVD-deficient rats made more premature responses and more head entries during longer inter-trial intervals (ITI than control rats. On the 5C-CPT AVD-deficient rats took longer to make false alarm (FA responses than control rats. AVD-deficient rats had increases in baseline GABA levels and the ratio of DOPAC/HVA within the striatum. CONCLUSIONS: AVD-deficient rats exhibited no major impairments in any of the behavioural domains tested. Impairments in premature responses in AVD-deficient rats may indicate that these animals have specific alterations in striatal systems governing compulsive or reward-seeking behaviour.

  16. Sex-Specific Skeletal Muscle Fatigability and Decreased Mitochondrial Oxidative Capacity in Adult Rats Exposed to Postnatal Hyperoxia

    Directory of Open Access Journals (Sweden)

    Laura H. Tetri

    2018-03-01

    Full Text Available Premature birth affects more than 10% of live births, and is characterized by relative hyperoxia exposure in an immature host. Long-term consequences of preterm birth include decreased aerobic capacity, decreased muscular strength and endurance, and increased prevalence of metabolic diseases such as type 2 diabetes mellitus. Postnatal hyperoxia exposure in rodents is a well-established model of chronic lung disease of prematurity, and also recapitulates the pulmonary vascular, cardiovascular, and renal phenotype of premature birth. The objective of this study was to evaluate whether postnatal hyperoxia exposure in rats could recapitulate the skeletal and metabolic phenotype of premature birth, and to characterize the subcellular metabolic changes associated with postnatal hyperoxia exposure, with a secondary aim to evaluate sex differences in this model. Compared to control rats, male rats exposed to 14 days of postnatal hyperoxia then aged to 1 year demonstrated higher skeletal muscle fatigability, lower muscle mitochondrial oxidative capacity, more mitochondrial damage, and higher glycolytic enzyme expression. These differences were not present in female rats with the same postnatal hyperoxia exposure. This study demonstrates detrimental mitochondrial and muscular outcomes in the adult male rat exposed to postnatal hyperoxia. Given that young adults born premature also demonstrate skeletal muscle dysfunction, future studies are merited to determine whether this dysfunction as well as reduced aerobic capacity is due to reduced mitochondrial oxidative capacity and metabolic dysfunction.

  17. Effect of sex on ethanol consumption and conditioned taste aversion in adolescent and adult rats.

    Science.gov (United States)

    Schramm-Sapyta, Nicole L; Francis, Reynold; MacDonald, Andrea; Keistler, Colby; O'Neill, Lauren; Kuhn, Cynthia M

    2014-04-01

    Vulnerability to alcoholism is determined by many factors, including the balance of pleasurable vs. aversive alcohol-induced sensations: pleasurable sensations increase intake, while aversive sensations decrease it. Female sex and adolescent age are associated with lower sensitivity to intake-reducing effects and more rapid development of alcohol abuse. This study assessed voluntary drinking and the aversive effects of alcohol to determine whether these measures are inversely related across the sexes and development. Voluntary drinking of 20 % ethanol in an every-other-day (EOD) availability pattern and the dose-response relationship of ethanol conditioned taste aversion (CTA) were assessed in male and female adolescent and adult rats. CTA was sex specific in adult but not adolescent rats, with adult females exhibiting less aversion. Voluntary ethanol consumption varied according to age and individual differences but was not sex specific. Adolescents initially drank more than adults, exhibited greater day-to-day variation in consumption, were more susceptible to the alcohol deprivation effect, and took longer to establish individual differences in consumption patterns. These results show that the emergence of intake patterns differs between adolescents and adults. Adolescents as a group initiate drinking at high levels but decrease intake as they mature. A subset of adolescents maintained high drinking levels into adulthood. In contrast, most adults consumed at steady, low levels, but a small subset quickly established and maintained high-consumption patterns. Adolescents also showed marked deprivation-induced increases. Sex differences were not observed in EOD drinking during either adolescence or adulthood.

  18. Effect of 8 weeks Resistance Training on BDNF and TrkB in the Hippocampus of Adult Male Rats

    Directory of Open Access Journals (Sweden)

    S Mojtahedi

    2014-08-01

    Full Text Available Background & aim: Exercise enhances the synaptic plasticity and neuroprotective effects in the adult brain. However, it remains unknown that how plasticity molecules change following types of training. The purpose of this study was to determine the effect of eight weeks resistance training on protein levels of Brain Derived Neurotrophic Factor(BDNF and receptor of TrkB, in the hippocampus of adult male rats. Methods: In this experimental study, twelve adult male rats, 8 weeks of age, with an average weight of 200 to 225 grams were randomly divided into two groups, control and exercise respectively. The exercise was to increase the weight on the ladder. 24 hours after their last training session. The animals were killed and the hippocampus was removed for further testing. ELISA determined changes in protein levels. Data were analyzed by independent t test. Results: There was a significant difference between train and control groups In protein level of variables statically (p≤0.05. In addition, protein levels of BDNF and TrkB in the hippocampus of rats increased. Conclusion: Resistance training is beneficial for promoting hippocampal plasticity associated with BDNF signaling and consequently functional and cognitive benefits.

  19. Prenatal exposure to vapors of gasoline-ethanol blends causes few cognitive deficits in adult rats

    Science.gov (United States)

    Developmental exposure to inhaled ethanol-gasoline fuel blends is a potential public health concern. Here we assessed cognitive functions in adult offspring of pregnant rats that were exposed to vapors of gasoline blended with a range of ethanol concentrations, including gasoli...

  20. [The reasonable use of right ventricular protection strategy in right ventricular outflow tract reconstruction].

    Science.gov (United States)

    Zhang, Y; Yuan, H Y; Liu, X B; Wen, S S; Xu, G; Cui, H J; Zhuang, J; Chen, J M

    2018-06-01

    As a result of right ventricular outflow tract reconstruction, which is the important and basic step of complex cardiac surgery, the blood flow of right ventricular outflow tract is unobstructed, while pulmonary valve regurgitation and right heart dysfunction could be happened. These problems are often ignored in early days, more and more cases of right heart dysfunction need clinical intervention, which is quite difficult and less effective. How to protect effectively the right ventricular function is the focus. At present main methods to protect the right ventricular function include trying to avoid or reduce length of right ventricular incision, reserving or rebuilding the function of the pulmonary valve, using growth potential material for surgery. The protection of the right ventricular function is a systemic project, it involves many aspects, single measures is difficult to provide complete protection, only the comprehensive use of various protection strategy, can help to improve the long-term prognosis.

  1. Mechanism of the negative force-frequency relationship in physiologically intact rat ventricular myocardium. Studies by intracellular Ca2+ monitor with iodo-1 and by 31P-nuclear magnetic resonance spectroscopy

    International Nuclear Information System (INIS)

    Morii, Isao; Kihara, Yasuki; Sasayama, Shigetake; Konishi, Takashi; Inubushi, Toshiro.

    1996-01-01

    We studied the subcellular mechanisms of the negative force-frequency relationship in rat myocardium by measuring intracellular Ca 2+ transients by indo-1 fluorometry and intracellular pH (pH i ) and phosphate compounds with 31 P-nuclear magnetic resonance (NMR). The data were compared with those from guinea pig hearts, which show a positive force-frequency relationship. By increasing the pacing rate from 3 Hz to 5 Hz, the peak positive first derivative of left ventricular pressure (LVdP/dt) in rat heart decreased by 10±1% (n=6). In contrast to this negative inotropic response, simultaneously measured peak Ca 2+ transients increased by 6±1%. Guinea pig heart (n=6) showed an increase in peak positive LVdP/dt (33±1%) which was associated with an increase in peak Ca 2+ transients (8±1%). Under equivalent experimental conditions in an NMR spectrometer, this increase in the pacing rate did not affect intracellular levels of phosphate compounds in either rat (n=6) or guinea pig heart (n=6). In contrast, pH i showed a decrease of 0.031±0.006 pH units in rat heart, while no changes were observed in guinea pig heart. These results suggest that in physiological rat myocardium, pH i is susceptible to changes in the stimulus frequency and may affect the Ca 2+ -responsiveness of contractile proteins, which results in the negative force-frequency relationship. (author)

  2. The effects of gonadectomy and binge-like ethanol exposure during adolescence on open field behaviour in adult male rats.

    Science.gov (United States)

    Yan, Wensheng; Kang, Jie; Zhang, Guoliang; Li, Shuangcheng; Kang, Yunxiao; Wang, Lei; Shi, Geming

    2015-09-14

    Binge drinking ethanol exposure during adolescence can lead to long-term neurobehavioural damage. It is not known whether the pubertal surge in testosterone that occurs during adolescence might impact the neurobehavioural effects of early ethanol exposure in adult animals. We examined this hypothesis by performing sham or gonadectomy surgeries on Sprague-Dawley rats around postnatal day (P) 23. From P28-65,the rats were administered 3.0g/kg ethanol using a binge-like model of exposure. Dependent measurements included tests of open field behaviour, blood ethanol concentrations, and testosterone levels. As adults, significant decreases in open field activity were observed in the GX rats. The open field behaviour of the GX rats was restored after testosterone administration. Binge-like ethanol exposure altered most of the parameters of the open field behaviour, suggestive of alcohol-induced anxiety, but rats treated with alcohol in combination with gonadectomy showed less motor behaviour and grooming behaviour and an increase in immobility, suggesting ethanol-induced depression. These results indicated that testosterone is required for ethanol-induced behavioural changes and that testicular hormones are potent stimulators of ethanol-induced behaviours. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Importance of neural mechanisms in colonic mucosal and muscular dysfunction in adult rats following neonatal colonic irritation.

    Science.gov (United States)

    Chaloner, A; Rao, A; Al-Chaer, E D; Greenwood-Van Meerveld, B

    2010-02-01

    Previous studies have shown that early life trauma induced by maternal separation or colonic irritation leads to hypersensitivity to colorectal distension in adulthood. We tested the hypothesis that repetitive colorectal distension in neonates leads to abnormalities in colonic permeability and smooth muscle function in the adult rat. In neonatal rats, repetitive colorectal distension was performed on days 8, 10, and 12. As adults, stool consistency was graded from 0 (formed stool) to 3 (liquid stool). Colonic tissue was isolated for histology and myeloperoxidase levels. The colonic mucosa was placed in modified Ussing chambers for measurements of permeability and short-circuit current responses to forskolin, electrical field stimulation, and carbachol. Segments of colonic musculature were placed in organ baths and contractile response to potassium chloride, electrical field stimulation, and carbachol were determined. In adult rats that experienced neonatal colonic irritation, no significant changes in colonic histology or myeloperoxidase activity were observed; however, stool consistency scores were increased. Mucosal permeability, measured as an increase in basal conductance, was significantly increased but no changes in short-circuit current responses were observed. In adulthood, rats that underwent colorectal distension as neonates exhibited an elevated smooth muscle contractile response to potassium chloride, but no changes in response to electrical field stimulation or carbachol. In summary, neonatal colonic irritation, shown previously to produce colonic hypersensitivity, leads to significant alterations in colonic mucosal and smooth muscle function characterized by loose stools, increased mucosal permeability, and increased smooth muscle contractility in the absence of colon inflammation in adulthood. Published by Elsevier Ltd.

  4. Estimated GFR and Subsequent Higher Left Ventricular Mass in Young and Middle-Aged Adults With Normal Kidney Function: The Coronary Artery Risk Development in Young Adults (CARDIA) Study.

    Science.gov (United States)

    Bansal, Nisha; Lin, Feng; Vittinghoff, Eric; Peralta, Carmen; Lima, Joao; Kramer, Holly; Shlipak, Michael; Bibbins-Domingo, Kirsten

    2016-02-01

    Left ventricular hypertrophy is common and is associated with cardiovascular events and death among patients with known chronic kidney disease. However, the link between reduced glomerular filtration rate (GFR) and left ventricular mass index (LVMI) remains poorly explored among young and middle-aged adults with preserved kidney function. In this study, we examined the association of cystatin C-based estimated GFR (eGFRcys) and rapid decline in eGFR with subsequent LVMI. Observational study. We included 2,410 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort with eGFRcys > 60mL/min/1.73m(2) at year 15 and who had an echocardiogram obtained at year 25. eGFRcys at year 15 and rapid decline in eGFRcys (defined as >3% per year over 5 years from years 15 to 20). LVMI measured at year 25. We adjusted for age, sex, race, diabetes, body mass index, low- and high-density lipoprotein cholesterol levels, cumulative systolic blood pressure, and albuminuria. Mean age was 40±4 (SD) years, 58% were women, and 43% were black. After 10 years of follow-up, mean LVMI was 39.6±13.4g/m(2.7). Compared with eGFRcys > 90mL/min/1.73m(2) (n = 2,228), eGFRcys of 60 to 75mL/min/1.73m(2) (n = 29) was associated with 5.63 (95% CI, 0.90-10.36) g/m(2.7) greater LVMI (P = 0.02), but there was no association of eGFRcys of 76 to 90mL/min/1.73m(2) (n = 153) with LVMI after adjustment for confounders. Rapid decline in eGFRcys was associated with higher LVMI compared with participants without a rapid eGFRcys decline (β coefficient, 1.48; 95% CI, 0.11-2.83; P = 0.03) after adjustment for confounders. There were a limited number of participants with eGFRcys of 60 to 90mL/min/1.73m(2). Among young and middle-aged adults with preserved kidney function, eGFRcys of 60 to 75mL/min/1.73m(2) and rapid decline in eGFRcys were significantly associated with subsequently higher LVMI. Further studies are needed to understand the mechanisms that contribute to elevated

  5. L-Arginine ameliorates cardiac left ventricular oxidative stress by upregulating eNOS and Nrf2 target genes in alloxan-induced hyperglycemic rats

    International Nuclear Information System (INIS)

    Ramprasath, Tharmarajan; Hamenth Kumar, Palani; Syed Mohamed Puhari, Shanavas; Senthil Murugan, Ponniah; Vasudevan, Varadaraj; Selvam, Govindan Sadasivam

    2012-01-01

    Highlights: ► L-Arginine treatment reduced the metabolic disturbances in diabetic animals. ► Antioxidant marker proteins were found high in myocardium by L-arginine treatment. ► Elevated antioxidant status, mediates the reduced TBA-reactivity in left ventricle. ► L-Arginine treatment enhanced the Nrf2 and eNOS signaling in left ventricle. ► Improved cell survival signaling by arginine, offers a novel tactic for targeting. -- Abstract: Hyperglycemia is independently related with excessive morbidity and mortality in cardiovascular disorders. L-Arginine-nitric oxide (NO) pathway and the involvement of NO in modulating nuclear factor-E2-related factor-2 (Nrf2) signaling were well established. In the present study we investigated, whether L-arginine supplementation would improve the myocardial antioxidant defense under hyperglycemia through activation of Nrf2 signaling. Diabetes was induced by alloxan monohydrate (90 mg kg −1 body weight) in rats. Both non-diabetic and diabetic group of rats were divided into three subgroups and they were administered either with L-arginine (2.25%) or L-NAME (0.01%) in drinking water for 12 days. Results showed that L-arginine treatment reduced the metabolic disturbances in diabetic rats. Antioxidant enzymes and glutathione levels were found to be increased in heart left ventricles, thereby reduction of lipid peroxidation by L-arginine treatment. Heart histopathological analysis further validates the reversal of typical diabetic characteristics consisting of alterations in myofibers and myofibrillary degeneration. qRT-PCR studies revealed that L-arginine treatment upregulated the transcription of Akt and downregulated NF-κB. Notably, transcription of eNOS and Nrf2 target genes was also upregulated, which were accompanied by enhanced expression of Nrf2 in left ventricular tissue from diabetic and control rats. Under these findings, we suggest that targeting of eNOS and Nrf2 signaling by L-arginine supplementation could be

  6. L-Arginine ameliorates cardiac left ventricular oxidative stress by upregulating eNOS and Nrf2 target genes in alloxan-induced hyperglycemic rats

    Energy Technology Data Exchange (ETDEWEB)

    Ramprasath, Tharmarajan; Hamenth Kumar, Palani; Syed Mohamed Puhari, Shanavas; Senthil Murugan, Ponniah; Vasudevan, Varadaraj [Molecular Cardiology Unit, Department of Biochemistry, Center for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai 625 021, Tamilnadu (India); Selvam, Govindan Sadasivam, E-mail: drselvamgsbiochem@rediffmail.com [Molecular Cardiology Unit, Department of Biochemistry, Center for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai 625 021, Tamilnadu (India)

    2012-11-23

    Highlights: Black-Right-Pointing-Pointer L-Arginine treatment reduced the metabolic disturbances in diabetic animals. Black-Right-Pointing-Pointer Antioxidant marker proteins were found high in myocardium by L-arginine treatment. Black-Right-Pointing-Pointer Elevated antioxidant status, mediates the reduced TBA-reactivity in left ventricle. Black-Right-Pointing-Pointer L-Arginine treatment enhanced the Nrf2 and eNOS signaling in left ventricle. Black-Right-Pointing-Pointer Improved cell survival signaling by arginine, offers a novel tactic for targeting. -- Abstract: Hyperglycemia is independently related with excessive morbidity and mortality in cardiovascular disorders. L-Arginine-nitric oxide (NO) pathway and the involvement of NO in modulating nuclear factor-E2-related factor-2 (Nrf2) signaling were well established. In the present study we investigated, whether L-arginine supplementation would improve the myocardial antioxidant defense under hyperglycemia through activation of Nrf2 signaling. Diabetes was induced by alloxan monohydrate (90 mg kg{sup -1} body weight) in rats. Both non-diabetic and diabetic group of rats were divided into three subgroups and they were administered either with L-arginine (2.25%) or L-NAME (0.01%) in drinking water for 12 days. Results showed that L-arginine treatment reduced the metabolic disturbances in diabetic rats. Antioxidant enzymes and glutathione levels were found to be increased in heart left ventricles, thereby reduction of lipid peroxidation by L-arginine treatment. Heart histopathological analysis further validates the reversal of typical diabetic characteristics consisting of alterations in myofibers and myofibrillary degeneration. qRT-PCR studies revealed that L-arginine treatment upregulated the transcription of Akt and downregulated NF-{kappa}B. Notably, transcription of eNOS and Nrf2 target genes was also upregulated, which were accompanied by enhanced expression of Nrf2 in left ventricular tissue from diabetic

  7. Protein synthesis in the rat brain: a comparative in vivo and in vitro study in immature and adult animals

    International Nuclear Information System (INIS)

    Shahbazian, F.M.

    1985-01-01

    Rates of protein synthesis of CNS and other organs were compared in immature and adult rats by in vivo and slice techniques with administration of flooding doses of labeled precursor. The relationship between synthesis and brain region, cell type, subcellular fraction, or MW was examined. Incorporation of [ 14 C]valine into protein of CNS regions in vivo was about 1.2% per hour for immature rats and 0.6% for adults. For slices, the rates decreased significantly more in adults. In adult organs, the highest synthesis rate in vivo was found in liver (2.2% per hour) followed by kidney, spleen, lung, heart, brain, and muscle (0.5% per hour). In immature animals synthesis was highest in liver and spleen (2.5% per hour) and lowest in muscle (0.9% per hour). Slices all showed lower rates than in vivo, especially in adults. In vivo, protein synthesis rates of immature neurons and astrocytes and adult neurons exceeded those of whole brain, while that in adult astrocytes was the same. These results demonstrate a developmental difference of protein synthesis (about double in immature animals) in all brain cells, cell fractions and most brain protein. Similarly the decreased synthesis in brain slices - especially in adults, affects most proteins and structural elements

  8. Radionuclide stroke count ratios for assessment of right and left ventricular volume overload in children

    International Nuclear Information System (INIS)

    Parrish, M.D.; Graham, T.P. Jr.; Born, M.L.; Jones, J.P.; Boucek, R.J. Jr.; Artman, M.; Partain, C.L.

    1983-01-01

    The ratio of left ventricular to right ventricular stroke counts measured by radionuclide angiography has been used in adults to estimate the severity of left-sided valvular regurgitation. The validation of this technique in children for assessment of right and left ventricular volume overload is reported herein. Radionuclide stroke count ratios in 60 children aged 0.5 to 19 years (mean 11) were determined. Based on their diagnoses, the patients were divided into 3 groups: (1) normal--40 patients with no shunts or valvular regurgitation, (2) left ventricular volume overload--13 patients with mitral or aortic regurgitation, or both, and (3) right ventricular volume overload--7 patients, 2 with severe tricuspid regurgitation, 3 with atrial septal defects, and 2 with total anomalous pulmonary venous drainage. The radionuclide stroke count ratio clearly differentiated these groups (p less than 0.05): normal patients had a stroke count ratio of 1.04 +/- 0.17 (mean +/- 1 standard deviation), the left ventricular volume overload group had a stroke count ratio of 2.43 +/- 0.86, and the right ventricular volume overload group had a stroke count ratio of 0.44 +/- 0.17. In 22 of our 60 patients, radionuclide stroke count ratios were compared with cineangiographic stroke volume ratios, resulting in a correlation coefficient of 0.88. It is concluded that radionuclide ventriculography is an excellent tool for qualitative and quantitative assessment of valvular regurgitation in children

  9. BAG3 regulates contractility and Ca(2+) homeostasis in adult mouse ventricular myocytes.

    Science.gov (United States)

    Feldman, Arthur M; Gordon, Jennifer; Wang, JuFang; Song, Jianliang; Zhang, Xue-Qian; Myers, Valerie D; Tilley, Douglas G; Gao, Erhe; Hoffman, Nicholas E; Tomar, Dhanendra; Madesh, Muniswamy; Rabinowitz, Joseph; Koch, Walter J; Su, Feifei; Khalili, Kamel; Cheung, Joseph Y

    2016-03-01

    Bcl2-associated athanogene 3 (BAG3) is a 575 amino acid anti-apoptotic protein that is constitutively expressed in the heart. BAG3 mutations, including mutations leading to loss of protein, are associated with familial cardiomyopathy. Furthermore, BAG3 levels have been found to be reduced in end-stage non-familial failing myocardium. In contrast to neonatal myocytes in which BAG3 is found in the cytoplasm and involved in protein quality control and apoptosis, in adult mouse left ventricular (LV) myocytes BAG3 co-localized with Na(+)-K(+)-ATPase and L-type Ca(2+) channels in the sarcolemma and t-tubules. BAG3 co-immunoprecipitated with β1-adrenergic receptor, L-type Ca(2+) channels and phospholemman. To simulate decreased BAG3 protein levels observed in human heart failure, we targeted BAG3 by shRNA (shBAG3) in adult LV myocytes. Reducing BAG3 by 55% resulted in reduced contraction and [Ca(2+)]i transient amplitudes in LV myocytes stimulated with isoproterenol. L-type Ca(2+) current (ICa) and sarcoplasmic reticulum (SR) Ca(2+) content but not Na(+)/Ca(2+) exchange current (INaCa) or SR Ca(2+) uptake were reduced in isoproterenol-treated shBAG3 myocytes. Forskolin or dibutyryl cAMP restored ICa amplitude in shBAG3 myocytes to that observed in WT myocytes, consistent with BAG3 having effects upstream and at the level of the receptor. Resting membrane potential and action potential amplitude were unaffected but APD50 and APD90 were prolonged in shBAG3 myocytes. Protein levels of Ca(2+) entry molecules and other important excitation-contraction proteins were unchanged in myocytes with lower BAG3. Our findings that BAG3 is localized at the sarcolemma and t-tubules while modulating myocyte contraction and action potential duration through specific interaction with the β1-adrenergic receptor and L-type Ca(2+) channel provide novel insight into the role of BAG3 in cardiomyopathies and increased arrhythmia risks in heart failure. Copyright © 2016 Elsevier Ltd. All rights

  10. BAG3 regulates contractility and Ca2+ homeostasis in adult mouse ventricular myocytes

    Science.gov (United States)

    Feldman, Arthur M.; Gordon, Jennifer; Wang, JuFang; Song, Jianliang; Zhang, Xue-Qian; Myers, Valerie D.; Tilley, Douglas G.; Gao, Erhe; Hoffman, Nicholas E.; Tomar, Dhanendra; Madesh, Muniswamy; Rabinowitz, Joseph; Koch, Walter J.; Su, Feifei; Khalili, Kamel; Cheung, Joseph Y.

    2016-01-01

    Bcl2-associated athanogene 3 (BAG3) is a 575 amino acid anti-apoptotic protein that is constitutively expressed in the heart. BAG3 mutations, including mutations leading to loss of protein, are associated with familial cardiomyopathy. Furthermore, BAG3 levels have been found to be reduced in end-stage non-familial failing myocardium. In contrast to neonatal myocytes in which BAG3 is found in the cytoplasm and involved in protein quality control and apoptosis, in adult mouse left ventricular (LV) myocytes BAG3 co-localized with Na+-K+-ATPase and L-type Ca2+ channels in the sarcolemma and t-tubules. BAG3 co-immunoprecipitated with β1-adrenergic receptor, L-type Ca2+ channels and phospholemman. To simulate decreased BAG3 protein levels observed in human heart failure, we targeted BAG3 by shRNA (shBAG3) in adult LV myocytes. Reducing BAG3 by 55% resulted in reduced contraction and [Ca2+]i transient amplitudes in LV myocytes stimulated with isoproterenol. L-type Ca2+ current (ICa) and sarcoplasmic reticulum (SR) Ca2+ content but not Na+/Ca2+ exchange current (INaCa) or SR Ca2+ uptake were reduced in isoproterenol-treated shBAG3 myocytes. Forskolin or dibutyrl cAMP restored ICa amplitude in shBAG3 myocytes to that observed in WT myocytes, consistent with BAG3 having effects upstream and at the level of the receptor. Resting membrane potential and action potential amplitude were unaffected but APD50 and APD90 were prolonged in shBAG3 myocytes. Protein levels of Ca2+ entry molecules and other important excitation-contraction proteins were unchanged in myocytes with lower BAG3. Our findings that BAG3 is localized at the sarcolemma and t-tubules while modulating myocyte contraction and action potential duration through specific interaction with the β1-adrenergic receptor and L-type Ca2+ channel provide novel insight into the role of BAG3 in cardiomyopathies and increased arrhythmia risks in heart failure. PMID:26796036

  11. Impact of experimental hypothyroidism on monoamines level in discrete brain regions and other peripheral tissues of young and adult male rats.

    Science.gov (United States)

    Hassan, Wafaa A; Aly, Mona S; Rahman, Taghride Abdel; Shahat, Asmaa S

    2013-06-01

    The levels of dopamine (DA), norepinephrine (NE) and serotonin (5-HT) in different brain regions as well as in blood plasma, cardiac muscle and adrenal gland of young and adult male albino rats were measured following experimentally induced hypothyroidism. Hypothyroidism induced by daily oral administration of propylthiouracil (PTU, 5mg/kg body wt) caused a significant reduction in DA levels in most of the tissues examined of both young and adult rats after 21 and 28 days, in NE levels after all the time intervals studied in young rats, and after 21 and 28 days in adult rats. 5-HT exhibited a significant reduction in the selected brain regions and blood plasma after 21 and 28 days and in cardiac muscle after all the time intervals in the two age groups of animals. It may be suggested that the changes in monoamine levels induced by hypothyroidism may be due to disturbance in the synthesis and release of these amines through the neurons impairment or may be due to an alteration pattern of their synthesizing and/or degradative enzymes. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.

  12. Acquisition of i.v. cocaine self-administration in adolescent and adult male rats selectively bred for high and low saccharin intake

    OpenAIRE

    Perry, Jennifer L.; Anderson, Marissa M.; Nelson, Sarah E.; Carroll, Marilyn E.

    2007-01-01

    Adolescence and excessive intake of saccharin have each been previously associated with enhanced vulnerability to drug abuse. In the present study, we focused on the relationship between these two factors using male adolescent and adult rats bred for high (HiS) and low (LoS) levels of saccharin intake. On postnatal day 25 (adolescents) or 150 (adults), rats were implanted with an intravenous catheter and trained to self-administer cocaine (0.4 mg/kg) using an autoshaping procedure that consis...

  13. Expression of Lymphatic Markers in the Adult Rat Spinal Cord.

    Science.gov (United States)

    Kaser-Eichberger, Alexandra; Schroedl, Falk; Bieler, Lara; Trost, Andrea; Bogner, Barbara; Runge, Christian; Tempfer, Herbert; Zaunmair, Pia; Kreutzer, Christina; Traweger, Andreas; Reitsamer, Herbert A; Couillard-Despres, Sebastien

    2016-01-01

    Under physiological conditions, lymphatic vessels are thought to be absent from the central nervous system (CNS), although they are widely distributed within the rest of the body. Recent work in the eye, i.e., another organ regarded as alymphatic, revealed numerous cells expressing lymphatic markers. As the latter can be involved in the response to pathological conditions, we addressed the presence of cells expressing lymphatic markers within the spinal cord by immunohistochemistry. Spinal cord of young adult Fisher rats was scrutinized for the co-expression of the lymphatic markers PROX1 and LYVE-1 with the cell type markers Iba1, CD68, PGP9.5, OLIG2. Rat skin served as positive control for the lymphatic markers. PROX1-immunoreactivity was detected in many nuclei throughout the spinal cord white and gray matter. These nuclei showed no association with LYVE-1. Expression of LYVE-1 could only be detected in cells at the spinal cord surface and in cells closely associated with blood vessels. These cells were found to co-express Iba1, a macrophage and microglia marker. Further, double labeling experiments using CD68, another marker found in microglia and macrophages, also displayed co-localization in the Iba1+ cells located at the spinal cord surface and those apposed to blood vessels. On the other hand, PROX1-expressing cells found in the parenchyma were lacking Iba1 or PGP9.5, but a significant fraction of those cells showed co-expression of the oligodendrocyte lineage marker OLIG2. Intriguingly, following spinal cord injury, LYVE-1-expressing cells assembled and reorganized into putative pre-vessel structures. As expected, the rat skin used as positive controls revealed classical lymphatic vessels, displaying PROX1+ nuclei surrounded by LYVE-1-immunoreactivity. Classical lymphatics were not detected in adult rat spinal cord. Nevertheless, numerous cells expressing either LYVE-1 or PROX1 were identified. Based on their localization and overlapping expression with

  14. Fourth ventricular ependymoma with a distant intraventricular metastasis: Report of a rare case

    Directory of Open Access Journals (Sweden)

    Sudheer Ambekar

    2013-01-01

    Full Text Available Ependymoma is one of the uncommon tumors of the central nervous system (CNS in the adult age group. These tumors have a distinct propensity for metastasis, both within and outside the CNS. However, dissemination at the time of first presentation and retrograde dissemination of the tumor is rare. We report the case of a patient with fourth ventricular anaplastic ependymoma who presented with left lateral ventricular metastasis which was anatomically different from the primary tumor. We describe the clinic-pathological detail of the patient and discuss the probable pathophysiological basis for this rare presentation and its significance in management of the patient.

  15. Transfer RNA methylases in rat placenta

    International Nuclear Information System (INIS)

    Jagtiani, S.K.; Narurkar, L.M.; Narurkar, M.V.

    1977-01-01

    Presence of tRNA methylases (5-adenosylmethionine : tRNA methyltransferases) was demonstrated at various stages of gestation in rat placenta, the enzyme being 50-100% higher than that of adult rat liver during early gestation. Placental tRNA methylases were shown to differ from those of liver in the extent of methylation. Glycine methyltransferase (S-adenosylmethionine : glycine methyltransferase), a regulatory enzyme in adult rat liver, was absent in placenta throughout gestation. The placental tRNA methylases could be inhibited in vitro by semipurified glycine methyltransferase from adult rat liver. The high placental tRNA methylase activity was comparable with the inhibitor-free enzyme activity of the adult rat liver. S-adenosyl-[Me- 14 C]-methionine was used in the investigation. (author)

  16. Effects of Chronic Exposure to Triclosan on Reproductive and Thyroid Endpoints in the Adult Wistar Female Rat

    Data.gov (United States)

    U.S. Environmental Protection Agency — This dataset includes the results of a long term adult female rat oral exposure to triclosan and includes hormone, estrous cyclicity, thyroid histology and liver...

  17. Prognostic impact of isolated right ventricular dysfunction in sepsis and septic shock: an 8-year historical cohort study.

    Science.gov (United States)

    Vallabhajosyula, Saraschandra; Kumar, Mukesh; Pandompatam, Govind; Sakhuja, Ankit; Kashyap, Rahul; Kashani, Kianoush; Gajic, Ognjen; Geske, Jeffrey B; Jentzer, Jacob C

    2017-09-07

    Echocardiographic myocardial dysfunction is reported commonly in sepsis and septic shock, but there are limited data on sepsis-related right ventricular dysfunction. This study sought to evaluate the association of right ventricular dysfunction with clinical outcomes in patients with severe sepsis and septic shock. Historical cohort study of adult patients admitted to all intensive care units at the Mayo Clinic from January 1, 2007 through December 31, 2014 for severe sepsis and septic shock, who had an echocardiogram performed within 72 h of admission. Patients with prior heart failure, cor-pulmonale, pulmonary hypertension and valvular disease were excluded. Right ventricular dysfunction was defined by the American Society of Echocardiography criteria. Outcomes included 1-year survival, in-hospital mortality and length of stay. Right ventricular dysfunction was present in 214 (55%) of 388 patients who met the inclusion criteria-isolated right ventricular dysfunction was seen in 100 (47%) and combined right and left ventricular dysfunction in 114 (53%). The baseline characteristics were similar between cohorts except for the higher mechanical ventilation use in patients with isolated right ventricular dysfunction. Echocardiographic findings demonstrated lower right ventricular and tricuspid valve velocities in patients with right ventricular dysfunction and lower left ventricular ejection fraction and increased mitral E/e' ratios in patients with combined right and left ventricular dysfunction. After adjustment for age, comorbidity, illness severity, septic shock and use of mechanical ventilation, isolated right ventricular dysfunction was independently associated with worse 1-year survival-hazard ratio 1.6 [95% confidence interval 1.2-2.1; p = 0.002) in patients with sepsis and septic shock. Isolated right ventricular dysfunction is seen commonly in sepsis and septic shock and is associated with worse long-term survival.

  18. The Effects of Early-Life Predator Stress on Anxiety- and Depression-Like Behaviors of Adult Rats

    Directory of Open Access Journals (Sweden)

    Lu-jing Chen

    2014-01-01

    Full Text Available Childhood emotional trauma contributes significantly to certain psychopathologies, such as post-traumatic stress disorder. In experimental animals, however, whether or not early-life stress results in behavioral abnormalities in adult animals still remains controversial. Here, we investigated both short-term and long-term changes of anxiety- and depression-like behaviors of Wistar rats after being exposed to chronic feral cat stress in juvenile ages. The 2-week predator stress decreased spontaneous activities immediately following stress but did not increase depression- or anxiety-like behaviors 4 weeks after the stimulation in adulthood. Instead, juvenile predator stress had some protective effects, though not very obvious, in adulthood. We also exposed genetic depression model rats, Wistar Kyoto (WKY rats, to the same predator stress. In WKY rats, the same early-life predator stress did not enhance anxiety- or depression-like behaviors in both the short-term and long-term. However, the stressed WKY rats showed slightly reduced depression-like behaviors in adulthood. These results indicate that in both normal Wistar rats and WKY rats, early-life predator stress led to protective, rather than negative, effects in adulthood.

  19. The Effects of Early-Life Predator Stress on Anxiety- and Depression-Like Behaviors of Adult Rats

    Science.gov (United States)

    Chen, Lu-jing; Shen, Bing-qing; Liu, Dan-dan; Li, Sheng-tian

    2014-01-01

    Childhood emotional trauma contributes significantly to certain psychopathologies, such as post-traumatic stress disorder. In experimental animals, however, whether or not early-life stress results in behavioral abnormalities in adult animals still remains controversial. Here, we investigated both short-term and long-term changes of anxiety- and depression-like behaviors of Wistar rats after being exposed to chronic feral cat stress in juvenile ages. The 2-week predator stress decreased spontaneous activities immediately following stress but did not increase depression- or anxiety-like behaviors 4 weeks after the stimulation in adulthood. Instead, juvenile predator stress had some protective effects, though not very obvious, in adulthood. We also exposed genetic depression model rats, Wistar Kyoto (WKY) rats, to the same predator stress. In WKY rats, the same early-life predator stress did not enhance anxiety- or depression-like behaviors in both the short-term and long-term. However, the stressed WKY rats showed slightly reduced depression-like behaviors in adulthood. These results indicate that in both normal Wistar rats and WKY rats, early-life predator stress led to protective, rather than negative, effects in adulthood. PMID:24839560

  20. Stable right ventricular size and function during short-term follow-up in patients with pulmonary regurgitation after tetralogy of Fallot repair

    International Nuclear Information System (INIS)

    Śpiewak, M.; Małek, Ł.A.; Petryka, J.; Biernacka, E.K.; Hoffman, P.; Demkow, M.; Miśko, J.; Rużyłło, W.

    2013-01-01

    Aim: To assess changes in ventricular size and function over time in conservatively treated adult patients with repaired tetralogy of Fallot (TOF) and significant pulmonary regurgitation (PR). Materials and methods: Patients with repaired TOF who had undergone more than one cardiac magnetic resonance study were identified. To confine the cause of ventricular size and function deviation to PR, patients with residual ventricular septal defect, more than mild regurgitation at a valve other than the pulmonary valve, and known coronary artery disease were excluded. Results: The final analysis included 27 adults with PR fraction >20%. During a follow-up of mean 2.1 ± 0.8 years, there was no change in right ventricular (RV) end-diastolic volume (EDV; 162.1 ± 27.6 versus 164 ± 29.6 ml/m 2 , p = 0.5). Left ventricular (LV) EDV showed a small decrease (85.1 ± 16.2 versus 81.5 ± 14.1 ml/m 2 , p = 0.02). The mean PR fraction, PR volume, and peak RV outflow tract gradient did not change. Additionally, both RV ejection fraction (EF) and LVEF remained stable over the follow-up period (48.1 ± 6.5 versus 48.4 ± 6.7%, p = 0.83, and 57.3 ± 5.4 versus 57.2 ± 5.1 %, p = 0.91, respectively). Only two asymptomatic patients (7.4% of the study group) developed symptoms and the remaining did not deteriorate. Conclusion: The RVEDV, RVEF, and LVEF remained stable over a mean follow-up of approximately 2 years in the majority of adult patients after TOF repair with significant PR and a wide range of RVEDV

  1. Effect of Nigella sativa Linn oil on tramadol-induced hepato- and nephrotoxicity in adult male albino rats

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    A. Elkhateeb

    2015-01-01

    Full Text Available The present study was carried out to evaluate the role of Nigella sativa Linn (NsL oil against subacute tramadol-induced hepatotoxicity, nephrotoxicity as well as oxidative stress in adult male albino rats. Sixty adult male albino rats were divided into four groups. Group I: control group; 30 rats equally subdivided into: Ia; −ve control group, Ib; +ve control group received saline, Ic; +ve control group received corn oil. Group II: 10 rats received NsL oil; 1 mg/kg in 1 ml corn oil/day, group III: 10 rats received tramadol; 30 mg/kg/day, group IV: 10 rats received tramadol + NsL oil in the previous doses. Treatments were given by gavage for 30 days. Then rats were sacrificed and specimens from the livers and kidneys were taken for biochemical and histopathological study. Biochemical data showed elevated liver enzymes; alanine transaminase (ALT, aspartate transaminase (AST, gamma glutamyltransferase (GGT, bilirubin as well as urea and creatinine in tramadol group. A significant increase in hepatic and renal malondialdehyde (MDA and a decrease in glutathione peroxidase (GPx levels were also noticed. Histological analysis of the liver showed vacuolated hepatocyte cytoplasm indicating hydropic degeneration with binucleated cells, apoptotic nuclei, congested central veins, cellular infiltration and hemorrhage. Kidney sections revealed atrophied glomeruli with collapsed tufts and wide Bowman's space, degenerated tubules, hemorrhage and mononuclear cellular infiltration. There was also an increase in area % of collagen fibers in both organs. Concomitant use of NsL oil with tramadol induced partial improvement in the hepato- and nephrotoxic effects. In conclusion, this study suggested that concomitant use of NsL oil with tramadol proved to be capable of ameliorating tramadol-induced hepato- and nephrotoxicity which might be due to its antioxidant potential.

  2. Right Ventricular Outflow Tract Tachycardia with Structural Abnormalities of the Right Ventricle and Left Ventricular Diverticulum

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    Bortolo Martini

    2015-01-01

    Full Text Available A 43-year-old woman presented to the emergency room with a sustained ventricular tachycardia (VT. ECG showed a QRS in left bundle branch block morphology with inferior axis. Echocardiography, ventricular angiography, and cardiac magnetic resonance imaging (CMRI revealed a normal right ventricle and a left ventricular diverticulum. Electrophysiology studies with epicardial voltage mapping identified a large fibrotic area in the inferolateral layer of the right ventricular wall and a small area of fibrotic tissue at the anterior right ventricular outflow tract. VT ablation was successfully performed with combined epicardial and endocardial approaches.

  3. The flavonoid quercetin reverses pulmonary hypertension in rats.

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    Daniel Morales-Cano

    Full Text Available Quercetin is a dietary flavonoid which exerts vasodilator, antiplatelet and antiproliferative effects and reduces blood pressure, oxidative status and end-organ damage in humans and animal models of systemic hypertension. We hypothesized that oral quercetin treatment might be protective in a rat model of pulmonary arterial hypertension. Three weeks after injection of monocrotaline, quercetin (10 mg/kg/d per os or vehicle was administered for 10 days to adult Wistar rats. Quercetin significantly reduced mortality. In surviving animals, quercetin decreased pulmonary arterial pressure, right ventricular hypertrophy and muscularization of small pulmonary arteries. Classic biomarkers of pulmonary arterial hypertension such as the downregulated expression of lung BMPR2, Kv1.5, Kv2.1, upregulated survivin, endothelial dysfunction and hyperresponsiveness to 5-HT were unaffected by quercetin. Quercetin significantly restored the decrease in Kv currents, the upregulation of 5-HT2A receptors and reduced the Akt and S6 phosphorylation. In vitro, quercetin induced pulmonary artery vasodilator effects, inhibited pulmonary artery smooth muscle cell proliferation and induced apoptosis. In conclusion, quercetin is partially protective in this rat model of PAH. It delayed mortality by lowering PAP, RVH and vascular remodeling. Quercetin exerted effective vasodilator effects in isolated PA, inhibited cell proliferation and induced apoptosis in PASMCs. These effects were associated with decreased 5-HT2A receptor expression and Akt and S6 phosphorylation and partially restored Kv currents. Therefore, quercetin could be useful in the treatment of PAH.

  4. Radionuclide analysis of right and left ventricular response to exercise in patients with atrial and ventricular septal defects

    International Nuclear Information System (INIS)

    Peter, C.A.; Bowyer, K.; Jones, R.H.

    1983-01-01

    In patients with ventricular or atrial septal defect, the ventricle which is chronically volume overloaded might not appropriately respond to increased demand for an augmentation in output and thereby might limit total cardiac function. In this study we simultaneously measured right and left ventricular response to exercise in 10 normal individuals, 10 patients with ventricular septal defect (VSD), and 10 patients with atrial septal defect (ASD). The normal subjects increased both right and left ventricular ejection fraction, end-diastolic volume, and stroke volume to achieve a higher cardiac output during exercise. Patients with VSD failed to increase right ventricular ejection fraction, but increased right ventricular end-diastolic volume and stroke volume. Left ventricular end-diastolic volume did not increase in these patients but ejection fraction, stroke volume, and forward left ventricular output achieved during exercise were comparable to the response observed in healthy subjects. In the patients with ASD, no rest-to-exercise change occurred in either right ventricular ejection fraction, end-diastolic volume, or stroke volume. In addition, left ventricular end-diastolic volume failed to increase, and despite an increase in ejection fraction, left ventricular stroke volume remained unchanged from rest to exercise. Therefore, cardiac output was augmented only by the heart rate increase in these patients. Right ventricular function appeared to be the major determinant of total cardiac output during exercise in patients with cardiac septal defects and left-to-right shunt

  5. Neurochemical Changes after Acute Binge Toluene Inhalation in Adolescent and Adult Rats: A High-Resolution Magnetic Resonance Spectroscopy Study

    Science.gov (United States)

    O'Leary-Moore, Shonagh K.; Galloway, Matthew P.; McMechan, Andrew P.; Irtenkauf, Susan; Hannigan, John H.; Bowen, Scott E.

    2009-01-01

    Inhalant abuse in young people is a growing public health concern. We reported previously that acute toluene intoxication in young rats, using a pattern of exposures that approximate abuse patterns of inhalant use in humans, significantly altered neurochemical measures in select brain regions. In this study, adolescent and young adult rats were exposed similarly to an acute (2 × 15 min), high dose (8000 − 12000 ppm) of toluene and high-resolution magic angle spinning proton magnetic resonance spectroscopy (HR-MAS 1H-MRS) was used to assess neurochemical profiles of tissue samples from a number of brain regions collected immediately following solvent exposure. The current investigation focused on N-acetyl-aspartate (NAA), choline-containing compounds, creatine, glutamate, GABA, and glutamine. Contrary to our predictions, no significant alterations were found in levels of NAA, choline, creatine, glutamate, or glutamine in adolescent animals. In contrast to these minimal effects in adolescents, binge toluene exposure altered several neurochemical parameters in young adult rats, including decreased levels of choline and GABA in the frontal cortex and striatum and lowered glutamine and NAA levels in the frontal cortex. One of the more robust findings was a wide-ranging increase in lactate after toluene exposure in adult animals, an effect not observed in adolescents. These age-dependent effects of toluene are distinct from those reported previously in juvenile rats and suggest a developmental difference in vulnerability to the effects of inhalants. Specifically, the results suggest that the neurochemical response to toluene in adolescents is attenuated compared to adults, and imply an association between these neurochemical differences and age-influenced differences in solvent abuse in humans. PMID:19628036

  6. Aconitine-induced Ca2+ overload causes arrhythmia and triggers apoptosis through p38 MAPK signaling pathway in rats

    International Nuclear Information System (INIS)

    Sun, Gui-bo; Sun, Hong; Meng, Xiang-bao; Hu, Jin; Zhang, Qiang; Liu, Bo; Wang, Min; Xu, Hui-bo; Sun, Xiao-bo

    2014-01-01

    Aconitine is a major bioactive diterpenoid alkaloid with high content derived from herbal aconitum plants. Emerging evidence indicates that voltage-dependent Na + channels have pivotal roles in the cardiotoxicity of aconitine. However, no reports are available on the role of Ca 2+ in aconitine poisoning. In this study, we explored the importance of pathological Ca 2+ signaling in aconitine poisoning in vitro and in vivo. We found that Ca 2+ overload lead to accelerated beating rhythm in adult rat ventricular myocytes and caused arrhythmia in conscious freely moving rats. To investigate effects of aconitine on myocardial injury, we performed cytotoxicity assay in neonatal rat ventricular myocytes (NRVMs), as well as measured lactate dehydrogenase level in the culture medium of NRVMs and activities of serum cardiac enzymes in rats. The results showed that aconitine resulted in myocardial injury and reduced NRVMs viability dose-dependently. To confirm the pro-apoptotic effects, we performed flow cytometric detection, cardiac histology, transmission electron microscopy and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay. The results showed that aconitine stimulated apoptosis time-dependently. The expression analysis of Ca 2+ handling proteins demonstrated that aconitine promoted Ca 2+ overload through the expression regulation of Ca 2+ handling proteins. The expression analysis of apoptosis-related proteins revealed that pro-apoptotic protein expression was upregulated, and anti-apoptotic protein BCL-2 expression was downregulated. Furthermore, increased phosphorylation of MAPK family members, especially the P-P38/P38 ratio was found in cardiac tissues. Hence, our results suggest that aconitine significantly aggravates Ca 2+ overload and causes arrhythmia and finally promotes apoptotic development via phosphorylation of P38 mitogen-activated protein kinase. - Highlights: • Aconitine-induced Ca 2+ overload causes arrhythmia in rats

  7. Inhibition of ErbB2 by receptor tyrosine kinase inhibitors causes myofibrillar structural damage without cell death in adult rat cardiomyocytes

    International Nuclear Information System (INIS)

    Pentassuglia, Laura; Graf, Michael; Lane, Heidi; Kuramochi, Yukio; Cote, Gregory; Timolati, Francesco; Sawyer, Douglas B.; Zuppinger, Christian; Suter, Thomas M.

    2009-01-01

    Inhibition of ErbB2 (HER2) with monoclonal antibodies, an effective therapy in some forms of breast cancer, is associated with cardiotoxicity, the pathophysiology of which is poorly understood. Recent data suggest, that dual inhibition of ErbB1 (EGFR) and ErbB2 signaling is more efficient in cancer therapy, however, cardiac safety of this therapeutic approach is unknown. We therefore tested an ErbB1-(CGP059326) and an ErbB1/ErbB2-(PKI166) tyrosine kinase inhibitor in an in-vitro system of adult rat ventricular cardiomyocytes and assessed their effects on 1. cell viability, 2. myofibrillar structure, 3. contractile function, and 4. MAPK- and Akt-signaling alone or in combination with Doxorubicin. Neither CGP nor PKI induced cardiomyocyte necrosis or apoptosis. PKI but not CGP caused myofibrillar structural damage that was additive to that induced by Doxorubicin at clinically relevant doses. These changes were associated with an inhibition of excitation-contraction coupling. PKI but not CGP decreased p-Erk1/2, suggesting a role for this MAP-kinase signaling pathway in the maintenance of myofibrils. These data indicate that the ErbB2 signaling pathway is critical for the maintenance of myofibrillar structure and function. Clinical studies using ErbB2-targeted inhibitors for the treatment of cancer should be designed to include careful monitoring for cardiac dysfunction.

  8. Four cases of right ventricular dysplasia

    International Nuclear Information System (INIS)

    Takamura, Ichiro; Ando, Joji; Miyamoto, Atsushi; Kobayashi, Takeshi; Sakamoto, Sanya; Yasuda, Hisakazu

    1985-01-01

    Finding of 81 Kr right ventriculography and 201 Tl myocardial perfusion imaging in 4 patients with right ventricular dysplasia (RVD) were compared with those in 28 patients with dilated cardiomyopathy. Remarkably dilated right ventricle was detected on 201 Tl myocardial perfusion imaging in the RVD group. In a patient with RVD who died suddenly, perfusion defect of the left ventricular myocardium, a decreased right ventricular ejection fraction, and an increased right ventricular end diastolic volume were seen. Perfusion defect of the left ventricular myocardium was seen in 10 of the 28 patients with dilated cardiomyopathy, 4 of whom died suddenly. In these 4 patients, a decreased left ventricular ejection fraction and an increased right ventricular end diastolic volume were seen. These findings obtained by the radionuclide techniques suggested that there are differences in cardiac dysfunction of the both ventricles between the groups with RVD and dilated cardiomyopathy. (Namekawa, K.)

  9. Beneficial Effects of Coenzyme Q10 in Reduction of Testicular Tissue Alteration Following Induction of Diabetes in Adult Rats

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    Kianifard Davoud

    2015-03-01

    Full Text Available Background and Aims: Various types of infertility are associated with uncontrolled hyperglycemia and diabetes. Development of oxidative stress is one the most important factors in the alteration of spermatogenesis in diabetic conditions. Consequently, the reduction of oxidative stress with antioxidant compounds can be effective in the reduction of tissue alterations. The aim of this study was to evaluate the efficacy of coenzyme Q10 in improvement of spermatogenesis in adult diabetic rats. Material and Methods: 32 adult rats were divided into four groups of control and treatment. Coenzyme Q10 (10 mg/kg body weight - b.w. was administrated to one control and one diabetic (intraperitoneal injection of 45 mg/kg b.w. of Streptozotocin groups. Blood concentrations of FSH, LH and Testosterone were measured. Histology of testicular tissue and sperm analysis were considered for evaluation of spermatogenesis. Results: Administration of Coenzyme Q10 led to increase of pituitary gonadotropins levels in diabetic rats. Testosterone levels were not changed significantly. Testicular morphology, spermatogenic indices and sperm analysis were improved in treated diabetic rats. Conclusions: The results of this study suggest that the use of Coenzyme Q10 has positive effects in reduction of spermatogenic alterations following induction of experimental diabetes in rats.

  10. Impact of chronic exposure to the pesticide chlorpyrifos on respiratory parameters and sleep apnea in juvenile and adult rats.

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    Walaa Darwiche

    Full Text Available The widely used organophosphorus pesticide chlorpyrifos (CPF is often detected in food. CPF inhibits acetylcholinesterase and can modify muscle contractility and respiratory patterns. We studied the effects of chronic exposure to CPF on respiratory parameters and diaphragm contractility in 21- and 60-days old rats. Pregnant rats were exposed to oral CPF (1 or 5 mg/ kg /day: CPF-1 or CPF-5 groups vs vehicle: controls from gestation onset up to weaning of the pups that were individually gavaged (CPF or vehicle thereafter. Two developmental time points were studied: weaning (day 21 and adulthood (day 60. Whole-body plethysmography was used to score breathing patterns and apnea index during sleep. Then, diaphragm strips were dissected for the assessment of contractility and acetylcholinesterase activity. Results showed that the sleep apnea index was higher in CPF-exposed rats than in controls. In adult rats, the expiratory time and tidal volume were higher in CPF-exposed animals than in controls. At both ages, the diaphragm's amplitude of contraction and fatigability index were higher in the CPF-5 group, due to lower acetylcholinesterase activity. We conclude that chronic exposure to CPF is associated with higher sleep apnea index and diaphragm contractility, and modifies respiratory patterns in sleeping juvenile and adult rats.

  11. Effects of chronic prenatal MK-801 treatment on object recognition, cognitive flexibility, and drug-induced locomotor activity in juvenile and adult rat offspring.

    Science.gov (United States)

    Gallant, S; Welch, L; Martone, P; Shalev, U

    2017-06-15

    Patients with schizophrenia display impaired cognitive functioning and increased sensitivity to psychomimetic drugs. The neurodevelopmental hypothesis of schizophrenia posits that disruption of the developing brain predisposes neural networks to lasting structural and functional abnormalities resulting in the emergence of such symptoms in adulthood. Given the critical role of the glutamatergic system in early brain development, we investigated whether chronic prenatal exposure to the glutamate NMDA receptor antagonist, MK-801, induces schizophrenia-like behavioural and neurochemical changes in juvenile and adult rats. Pregnant Long-Evans rats were administered saline or MK-801 (0.1mg/kg; s.c.) at gestation day 7-19. Object recognition memory and cognitive flexibility were assessed in the male offspring using a novel object preference task and a maze-based set-shifting procedure, respectively. Locomotor-activating effects of acute amphetamine and MK-801 were also assessed. Adult, but not juvenile, prenatally MK-801-treated rats failed to show novel object preference after a 90min delay, suggesting that object recognition memory may have been impaired. In addition, the set-shifting task revealed impaired acquisition of a new rule in adult prenatally MK-801-treated rats compared to controls. This deficit appeared to be driven by regression to the previously learned behaviour. There were no significant differences in drug-induced locomotor activity in juvenile offspring or in adult offspring following acute amphetamine challenges. Unexpectedly, MK-801-induced locomotor activity in adult prenatally MK-801-treated rats was lower compared to controls. Glutamate transmission dysfunction during early development may modify behavioural parameters in adulthood, though these parameters do not appear to model deficits observed in schizophrenia. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Astrocytes from adult Wistar rats aged in vitro show changes in glial functions.

    Science.gov (United States)

    Souza, Débora Guerini; Bellaver, Bruna; Raupp, Gustavo Santos; Souza, Diogo Onofre; Quincozes-Santos, André

    2015-11-01

    Astrocytes, the most versatile cells of the central nervous system, play an important role in the regulation of neurotransmitter homeostasis, energy metabolism, antioxidant defenses and the anti-inflammatory response. Recently, our group characterized cortical astrocyte cultures from adult Wistar rats. In line with that work, we studied glial function using an experimental in vitro model of aging astrocytes (30 days in vitro after reaching confluence) from newborn (NB), adult (AD) and aged (AG) Wistar rats. We evaluated metabolic parameters, such as the glucose uptake, glutamine synthetase (GS) activity, and glutathione (GSH) content, as well as the GFAP, GLUT-1 and xCT expression. AD and AG astrocytes take up less glucose than NB astrocytes and had decreased GLUT1 expression levels. Furthermore, AD and AG astrocytes exhibited decreased GS activity compared to NB cells. Simultaneously, AD and AG astrocytes showed an increase in GSH levels, along with an increase in xCT expression. NB, AD and AG astrocytes presented similar morphology; however, differences in GFAP levels were observed. Taken together, these results improve the knowledge of cerebral senescence and represent an innovative tool for brain studies of aging. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. 11beta-hydroxysteroid dehydrogenase type 2 expression in the newly formed Leydig cells after ethane dimethanesulphonate treatment of adult rats.

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    Katerina Georgieva

    2008-01-01

    Full Text Available The enzyme 11beta-hydroxysteroid dehydrogenase (11beta-HSD catalyzes the reversible conversion of physiologically active corticosterone to the biologically inert 11beta-dehydrocorticosterone in rat testis and protect the Leydig cells (LCs against the suppressive effect of glucocorticoids. The developmental pathway of the adult LCs population is accompanied with an increase in the 11beta-HDS activity. Thus, 11beta-HDS together with its role in controlling the toxicological effect of glucocorticoids on LCs can be used as a marker for their functional maturity. Ethane 1,2-dimethanesulphonate (EDS treatment of adult rats become unique appropriate model, which enable to answer many questions related to the differentiation of adult LCs in the prepubertal rat testis. The aim of the present study was to investigate the specific changes in the 11beta-HDS type 2 immunoreactivity in tandem with the expression of androgen receptor (AR during renewal of LCs population after EDS treatment. In the present study, we observed the first appearance of immunostaining for 11beta-HSD2 in new LCs population on day 14 after EDS administration when the progenitor LCs were detected. Our immunohistochemical analysis revealed progressive increases in the 11beta-HSD2 reaction intensity on 21 days after EDS treatment and reached a maximum on day 35. AR immunoexpression was found in new LCs on day 14 and 21 after EDS injection with an increasing curve of intensity. The most prominent AR immunostaining in new population LCs was evident by 35 days after EDS and that coincided with the increased number of LCs and restoration of adult LCs population. Our results demonstrated similar pattern of immunoreactivity for 11beta-HSD2 and AR in new LCs population after EDS treatment and suggested that the changes in 11beta-HSD2 expression can be used for evaluation of adult LCs differentiation in rat testis.

  14. Adenosine A1 receptor antagonist mitigates deleterious effects of sleep deprivation on adult neurogenesis and spatial reference memory in rats.

    Science.gov (United States)

    Chauhan, G; Ray, K; Sahu, S; Roy, K; Jain, V; Wadhwa, M; Panjwani, U; Kishore, K; Singh, S B

    2016-11-19

    Sleep deprivation (SD) upsurges intracellular levels of adenosine, impairs adult neuronal cell proliferation (NCP) and cognition while caffeine, a non-selective adenosine A1 receptor (A1R) antagonist improves cognition and adult NCP during SD. We examined the selective antagonistic effects of adenosine A1R using 8-cyclopentyl-1,3-dimethylxanthine (8-CPT) on impairment of spatial reference memory and adult NCP during 48h SD. Adult male Sprague Dawley rats were sleep deprived for 48h, using an automatic cage vibrating stimulus based on animal activity. Spatial reference memory was tested as a measure of cognitive performance employing Morris Water Maze. Rats were given 8-CPT dissolved in 50% dimethyl sulfoxide (DMSO), twice daily (10mg/kg, i.p.) along with 5-bromo-2-deoxyuridine (BrdU) (50mg/kg/day, i.p.). The rats treated with 8-CPT showed significantly short mean latency and path-length to reach the platform compared to the SD rats. Consistent with these findings, 8-CPT-treated group was found to have significantly increased the number of BrdU, Ki-67 and doublecortin (DCX) positive cells. However, no significant difference was seen in NeuN expression in the Dentate Gyrus (DG). Brain-derived neurotropic factor (BDNF) expression in the DG and CA1 region was observed to decrease significantly after SD and be rescued by 8-CPT treatment. Furthermore, latency to reach platform showed a negative correlation with number of BrdU, DCX type-1 cells and BDNF expression in DG. Thus, it may be concluded that treatment with 8-CPT, an adenosine A1R antagonist during SD mitigates SD induced decline in spatial reference memory and adult NCP possibly via up regulation of BDNF levels in DG and CA1 regions. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  15. Large right ventricular sinusoids in an infant with aorta-left ventricular tunnel and proximal right coronary artery atresia.

    Science.gov (United States)

    Chen, Peter C; Spinner, Joseph A; Heinle, Jeffrey S

    2018-07-01

    We report a 1-month-old infant diagnosed with an aorta-left ventricular tunnel, ventricular septal defect, and right coronary atresia with right ventricular sinusoids. The patient's anatomy and physiology did not indicate right-ventricular-dependent coronary circulation, and therefore right ventricular decompression could be performed without compromising coronary perfusion during surgical correction. A detailed understanding of the coronary anatomy is critical in managing this defect when coronary anomalies are present.

  16. Efeitos da estimulação ventricular convencional em pacientes com função ventricular normal Efectos de la estimulación ventricular convencional en pacientes con función ventricular normal Conventional ventricular stimulation effects on patients with normal ventricular function

    Directory of Open Access Journals (Sweden)

    Luiz Antonio Batista de Sá

    2009-08-01

    Full Text Available FUNDAMENTO: A estimulação de ventrículo direito pode ser deletéria em pacientes com disfunção ventricular, entretanto há poucas evidências sobre o impacto dessa estimulação em pacientes com função normal. OBJETIVO: Avaliar a evolução clínica e laboratorial de pacientes com função ventricular normal submetidos a implante de marcapasso cardíaco artificial. MÉTODOS: Foram estudados de forma prospectiva 16 pacientes com os seguintes critérios de inclusão: função ventricular normal definida pelo ecocardiograma e presença de estimulação ventricular superior 90% (avaliação por telemetria do gerador. Parâmetros analisados: classe funcional (CF, teste de caminhada, dosagem de BNP, ecocardiograma (convencional e parâmetros de dessincronia intraventricular e teste de qualidade de vida (SF36. Essas medidas fora feitas com 10 dias(d (t1, 120d(t2 e 240 d(t3. Os dados foram comparados ao longo do tempo segundo método ANOVA. Comparações múltiplas de médias foram efetuadas utilizando-se o método de Tukey. RESULTADOS: Dos dados avaliados os seguintes não apresentaram variação estatística significante (p>0,05: classe funcional, dosagem de BNP, parâmetros ecocardiográficos convencionais, dessincronia intraventricular (Doppler tecidual. Apresentaram piora (pFUNDAMENTO: La estimulación del ventrículo derecho puede ser dañosa a pacientes con disfunción ventricular. Sin embargo, hay pocas evidencias sobre el impacto de esa estimulación en pacientes con función normal. OBJETIVO: Evaluar la evolución clínica y laboratorial de pacientes con función ventricular normal sometidos a implante de marcapaso cardíaco artificial. MÉTODOS: Se estudiaron de forma prospectiva a 16 pacientes con los siguientes criterios de inclusión: función ventricular normal definida por el ecocardiograma y presencia de estimulación ventricular superior a 90% (evaluación por telemetría del generador. Parámetros analizados: clase funcional

  17. In vivo study about specific captation of 125 I-insulin by rat brain structures

    International Nuclear Information System (INIS)

    Sanvitto, G.L.

    1986-01-01

    The specific captation of 125 I-insulin was evaluated by brain structures, as olfactory bulbous, hypothalamus and cerebellum in rats, from in vivo experiences that including two different aspects: captation measure of 125 I-insulin after the intravenous injection of the labelled hormone, in fed rats and in rats with 48 h of fast or convulsion, procedure by the pentylene tetrazole; captation measure of 125 I-insulin after intra-cerebral-ventricular injection of the labelled hormone in fed rats. (C.G.C.)

  18. Association of obesity in early adulthood and middle age with incipient left ventricular dysfunction and structural remodeling: the CARDIA study (Coronary Artery Risk Development in Young Adults).

    Science.gov (United States)

    Kishi, Satoru; Armstrong, Anderson C; Gidding, Samuel S; Colangelo, Laura A; Venkatesh, Bharath A; Jacobs, David R; Carr, J Jeffery; Terry, James G; Liu, Kiang; Goff, David C; Lima, João A C

    2014-10-01

    The goal of this study was to investigate the relationship of body mass index (BMI) and its 25-year change to left ventricular (LV) structure and function. Longstanding obesity may be associated with clinical cardiac dysfunction and heart failure. Whether obesity relates to cardiac dysfunction during young adulthood and middle age has not been investigated. The CARDIA (Coronary Artery Risk Development in Young Adult) study enrolled white and black adults ages 18 to 30 years in 1985 to 1986 (Year-0). At Year-25, cardiac function was assessed by conventional echocardiography, tissue Doppler imaging (TDI), and speckle tracking echocardiography (STE). Twenty-five-year change in BMI (classified as low: obesity from young adulthood to middle age is associated with impaired LV systolic and diastolic function assessed by conventional echocardiography, TDI, and STE in a large biracial cohort of adults age 43 to 55 years. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  19. Neurological assessments after treatment with the antimalarial β-arteether in neonatal and adult rats.

    Science.gov (United States)

    Erickson, R I; Defensor, E B; Fairchild, D G; Mirsalis, J C; Steinmetz, K L

    2011-08-01

    The World Health Organization currently recommends combinatorial treatment including artemisinins as first-line therapy against drug-resistant Plasmodium falciparum malaria. Although highly efficacious, artemisinin and its derivatives, including β-arteether (βAE), are associated with ototoxicity, tremors, and other autonomic and motor impairments in the clinic. Similar neurological symptoms, as well as brainstem lesions, have been observed in adult laboratory species (mice, rats, dogs, and non human primates) following acute treatment with βAE; however, few long-term, nonclinical studies have been conducted. Furthermore, the majority of deaths attributed to malarial infection occur in children under age five, yet no laboratory studies have been initiated in neonatal or juvenile animals. In the current study, neonatal 7-day-old rats were administered intramuscular doses of 1-90 mg/kg βAE in sesame oil for up to eight treatment cycles (one cycle=7 days treatment+7 days without treatment). Neonates were tested for changes in sensorimotor function, and the same animals were tested as adults in the Functional Observational Battery, for motor activity, and in the 8-arm radial maze. Pups receiving a single cycle of 60 or 90 mg/kg died within a week of treatment but had few behavioral changes and no brainstem pathology. In the long-term study, behavioral and motor changes and brainstem lesions were observed in a dose- and time-related manner. Rats given repeated cycles of 1 or 5mg/kg βAE showed subtle motor abnormalities (e.g., slight loss of righting reflex) while repeated cycles of 10mg/kg βAE treatment resulted in obvious motor and behavioral changes. Rats receiving 1mg/kg βAE had no brainstem lesions whereas some rats treated with 5mg/kg βAE and all rats treated with 10 mg/kg βAE had brainstem lesions. Brainstem lesions were observed after as few as five cycles and were characterized by gliosis, satellitosis and progressive necrosis in motor neurons of the

  20. Effects of Maternal Behavior Induction and Pup Exposure on Neurogenesis in Adult, Virgin Female Rats

    Science.gov (United States)

    Furuta, Miyako; Bridges, Robert S.

    2009-01-01

    The states of pregnancy and lactation bring about a range of physiological and behavioral changes in the adult mammal that prepare the mother to care for her young. Cell proliferation increases in the subventricular zone (SVZ) of the female rodent brain during both pregnancy and lactation when compared to that in cycling, diestrous females. In the present study, the effects of maternal behavior induction and pup exposure on neurogenesis in nulliparous rats were examined in order to determine whether maternal behavior itself, independent of pregnancy and lactation, might affect neurogenesis. Adult, nulliparous, Sprague-Dawley, female rats were exposed daily to foster young in order to induce maternal behavior. Following the induction of maternal behavior each maternal subject plus females that were exposed to pups for a comparable number of test days, but did not display maternal behavior, and subjects that had received no pup exposure were injected with bromodeoxyuridine (BrdU, 90 mg/kg, i.v.). Brain sections were double-labeled for BrdU and the neural marker, NeuN, to examine the proliferating cell population. Increases in the number of double-labeled cells were found in the maternal virgin brain when compared with the number of double-labeled cells present in non-maternal, pup-exposed nulliparous rats and in females not exposed to young. No changes were evident in the dentate gyrus of the hippocampus as a function of maternal behavior. These data indicate that in nulliparous female rats maternal behavior itself is associated with the stimulation of neurogenesis in the SVZ. PMID:19712726

  1. Chronic Oral Capsaicin Exposure During Development Leads to Adult Rats with Reduced Taste Bud Volumes.

    Science.gov (United States)

    Omelian, Jacquelyn M; Samson, Kaeli K; Sollars, Suzanne I

    2016-09-01

    Cross-sensory interaction between gustatory and trigeminal nerves occurs in the anterior tongue. Surgical manipulations have demonstrated that the strength of this relationship varies across development. Capsaicin is a neurotoxin that affects fibers of the somatosensory lingual nerve surrounding taste buds, but not fibers of the gustatory chorda tympani nerve which synapse with taste receptor cells. Since capsaicin is commonly consumed by many species, including humans, experimental use of this neurotoxin provides a naturalistic perturbation of the lingual trigeminal system. Neonatal or adults rats consumed oral capsaicin for 40 days and we examined the cross-sensory effect on the morphology of taste buds across development. Rats received moderate doses of oral capsaicin, with chronic treatments occurring either before or after taste system maturation. Tongue morphology was examined either 2 or 50 days after treatment cessation. Edema, which has been previously suggested as a cause of changes in capsaicin-related gustatory function, was also assessed. Reductions in taste bud volume occurred 50 days, but not 2 days post-treatment for rats treated as neonates. Adult rats at either time post-treatment were unaffected. Edema was not found to occur with the 5 ppm concentration of capsaicin we used. Results further elucidate the cooperative relationship between these discrete sensory systems and highlight the developmentally mediated aspect of this interaction. Chronic exposure to even moderate levels of noxious stimuli during development has the ability to impact the orosensory environment, and these changes may not be evident until long after exposure has ceased.

  2. Quantification of the rat left ventricle force and Ca2+ -frequency relationships: similarities to dog and human.

    Science.gov (United States)

    Taylor, David G; Parilak, Leonard D; LeWinter, Martin M; Knot, Harm J

    2004-01-01

    To measure and quantify the force-frequency (FFR) and Ca(2+)-frequency (CaFR) relationships in isolated rat left ventricular (LV) muscle at physiological heart rates and compare the obtained FFR to that measured in larger mammalian muscle from dog and human using the same experimental protocol. Rat papillary muscle was isolated from the LV of adult male Sprague-Dawley rats, and dog and human muscles were from free-wall LV biopsies, loaded with the Ca(2+) indicator Fura-2, allowed to recover from isolation trauma and then subjected to direct electrical stimulation while measuring force production and intracellular Ca(2+) transients. We obtained a positive FFR between 1 and 4 Hz that is qualitatively similar to that found in isolated LV epicardial muscle strips from dogs and humans with normal LV function. The FFR reflects the cytosolic Ca(2+) transients in amplitude. Isoproterenol yielded an enhancement in force, but flattening of the FFR, whereas cyclopiazonic acid caused depression of FFR amplitude without changing frequency-dependent shape. We describe an experimental protocol that consistently yields positive FFRs in rat, dog and human LV muscle at stimulation rates between 1 and 4 Hz, without significant qualitative differences. We attribute previously observed negative FFR in rat muscle to an increase in SERCA activity early after excision and preparation of the muscle strips.

  3. Role of ventricular tachycardia ablation in arrhythmogenic right ventricular cardiomyopathy

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    Alberto Cipriani

    2017-11-01

    Full Text Available Arrhythmogenic right ventricular cardiomyopathy (ARVC is characterized by progressive fibro-fatty replacement of the myocardium that represents the substrate for recurrent sustained ventricular tachycardia (VT. These arrhythmias characterize the clinical course of a sizeable proportion of patients and have significant implications for their quality of life and long-term prognosis. Antiarrhythmic drugs are often poorly tolerated and usually provide incomplete control of arrhythmia relapses. Catheter ablation is a potentially effective strategy to treat frequent VT episodes and ICD shocks in ARVC patients. The aims of this review are to discuss the electrophysiological and electroanatomic substrates of ventricular tachycardia in patients with ARVC and to analyze the role of catheter ablation in their management with particular reference to selection of patients, technical issues, potential complications and outcomes.

  4. The effects of cinnamon on glycemic indexes and insulin resistance in adult male diabetic rats with streptozotocin

    OpenAIRE

    SEbrahim Hosseini; STaereh Shojaei; SAli Hosseini

    2015-01-01

    Background: Diabetes is a common disease that for its treatment and control different methods are recommended such as the use of natural remedies and lifestyle modification. Since the use of herbal medicines have less side effects than many chemical drugs, hence, this study aimed to investigate the effect of cinnamon extract on blood glucose, insulin and insulin resistance in diabetic rats with streptozotocin. Materials and Methods: This experimental study was conducted on 40 adult male rats,...

  5. Toxicity Induced after Subchronic Administration of the Synthetic Food Dye Tartrazine in Adult Rats, Role of Oxidative Stress

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    Narges El Golli

    2016-04-01

    Full Text Available The present study was conducted to evaluate the toxic potential of tartrazine, a food color, in different tissues in adult rat: blood, liver, kidneys, and spleen. Tartrazine was administered orally at a dose of 300 mg/kg of body weight to adult male Wistar rats during a period of 30 days. Tartrazine treatment led to an increase in platelets count, a reduction in peripheral lymphocytes and in spleen T CD8-lymphocytes. Furthermore, tartrazine increased the activities of hepatocellular enzymes and promoted changes in kidney biomarkers. In order to explore the possible mechanism involved, oxidative-stress assessment was performed. Results identified critical oxidative alterations in all tested organs, as shown by the promotion of lipid peroxidation and the modification of endogenous antioxidant-defense enzymes. Thus, tartrazine is able to induce in adult rats’ hematotoxicity, immunotoxicity, and liver and kidney injuries by changing the whole balance between oxidants and antioxidants.

  6. Aconitine-induced Ca{sup 2+} overload causes arrhythmia and triggers apoptosis through p38 MAPK signaling pathway in rats

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Gui-bo; Sun, Hong; Meng, Xiang-bao [Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193 (China); Hu, Jin; Zhang, Qiang; Liu, Bo [Academy of Chinese Medical Sciences of Jilin Province, Changchun, Jilin 130021 (China); Wang, Min [Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193 (China); Xu, Hui-bo, E-mail: xhb_6505@163.com [Academy of Chinese Medical Sciences of Jilin Province, Changchun, Jilin 130021 (China); Sun, Xiao-bo, E-mail: sun_xiaobo163@163.com [Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193 (China)

    2014-08-15

    Aconitine is a major bioactive diterpenoid alkaloid with high content derived from herbal aconitum plants. Emerging evidence indicates that voltage-dependent Na{sup +} channels have pivotal roles in the cardiotoxicity of aconitine. However, no reports are available on the role of Ca{sup 2+} in aconitine poisoning. In this study, we explored the importance of pathological Ca{sup 2+} signaling in aconitine poisoning in vitro and in vivo. We found that Ca{sup 2+} overload lead to accelerated beating rhythm in adult rat ventricular myocytes and caused arrhythmia in conscious freely moving rats. To investigate effects of aconitine on myocardial injury, we performed cytotoxicity assay in neonatal rat ventricular myocytes (NRVMs), as well as measured lactate dehydrogenase level in the culture medium of NRVMs and activities of serum cardiac enzymes in rats. The results showed that aconitine resulted in myocardial injury and reduced NRVMs viability dose-dependently. To confirm the pro-apoptotic effects, we performed flow cytometric detection, cardiac histology, transmission electron microscopy and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay. The results showed that aconitine stimulated apoptosis time-dependently. The expression analysis of Ca{sup 2+} handling proteins demonstrated that aconitine promoted Ca{sup 2+} overload through the expression regulation of Ca{sup 2+} handling proteins. The expression analysis of apoptosis-related proteins revealed that pro-apoptotic protein expression was upregulated, and anti-apoptotic protein BCL-2 expression was downregulated. Furthermore, increased phosphorylation of MAPK family members, especially the P-P38/P38 ratio was found in cardiac tissues. Hence, our results suggest that aconitine significantly aggravates Ca{sup 2+} overload and causes arrhythmia and finally promotes apoptotic development via phosphorylation of P38 mitogen-activated protein kinase. - Highlights: • Aconitine-induced Ca

  7. Effect of single x-irradiation on glucocorticoid function of adrenal glands of adult and old rats

    International Nuclear Information System (INIS)

    Gorban', Je.M.; Topol'nyikova, N.V.

    2001-01-01

    The peculiarities of short-term (1 h, 1 day) adrenal glucocorticoid function in adult and old rats after single x-irradiation at different doses was studied. changes in the glucocorticoid function of the adrenal glands at studied terms after single x-irradiation at used doses were observed in adult but not in old animals. This testifies to an age-related decrease in the range of adaptive possibilities of this link of the organism adaptive system to x-irradiation effects

  8. Dynamic Changes of QRS Morphology of Premature Ventricular Contractions During Ablation in the Right Ventricular Outflow Tract: A Case Report.

    Science.gov (United States)

    Yue-Chun, Li; Jia-Feng, Lin; Jia-Xuan, Lin

    2015-10-01

    Electrocardiographic characteristics can be useful in differentiating between right ventricular outflow tract (RVOT) and aortic sinus cusp (ASC) ventricular arrhythmias. Ventricular arrhythmias originating from ASC, however, show preferential conduction to RVOT that may render the algorithms of electrocardiographic characteristics less reliable. Even though there are few reports describing ventricular arrhythmias with ASC origins and endocardial breakout sites of RVOT, progressive dynamic changes in QRS morphology of the ventricular arrhythmias during ablation obtained were rare.This case report describes a patient with symptomatic premature ventricular contractions of left ASC origin presenting an electrocardiogram (ECG) characteristic of right ventricular outflow tract before ablation. Pacing at right ventricular outflow tract reproduced an excellent pace map. When radiofrequency catheter ablation was applied to the right ventricular outflow tract, the QRS morphology of premature ventricular contractions progressively changed from ECG characteristics of right ventricular outflow tract origin to ECG characteristics of left ASC origin.Successful radiofrequency catheter ablation was achieved at the site of the earliest ventricular activation in the left ASC. The distance between the successful ablation site of the left ASC and the site with an excellent pace map of the RVOT was 20 mm.The ndings could be strong evidence for a preferential conduction via the myocardial bers from the ASC origin to the breakout site in the right ventricular outflow tract. This case demonstrates that ventricular arrhythmias with a single origin and exit shift may exhibit QRS morphology changes.

  9. Epilepsy is associated with ventricular alterations following convulsive status epilepticus in children.

    Science.gov (United States)

    Ali, Wail; Bubolz, Beth A; Nguyen, Linh; Castro, Danny; Coss-Bu, Jorge; Quach, Michael M; Kennedy, Curtis E; Anderson, Anne E; Lai, Yi-Chen

    2017-12-01

    Convulsive status epilepticus can exert profound cardiovascular effects in adults including ventricular depolarization-repolarization abnormalities. Whether status epilepticus adversely affects ventricular electrical properties in children is less understood. Therefore, we sought to characterize ventricular alterations and the associated clinical factors in children following convulsive status epilepticus. We conducted a 2-year retrospective, case-control study. Children between 1 month and 21 years of age were included if they were admitted to the pediatric intensive care unit with primary diagnosis of convulsive status epilepticus and had 12-lead electrocardiogram (ECG) within 24 hours of admission. Children with heart disease, ion channelopathy, or on vasoactive medications were excluded. Age-matched control subjects had no history of seizures or epilepsy. The primary outcome was ventricular abnormalities represented by ST segment changes, abnormal T wave, QRS axis deviation, and corrected QT (QTc) interval prolongation. The secondary outcomes included QT/RR relationship, beat-to-beat QTc interval variability, ECG interval measurement between groups, and clinical factors associated with ECG abnormalities. Of 317 eligible children, 59 met the inclusion criteria. History of epilepsy was present in 31 children (epileptic) and absent in 28 children (non-epileptic). Compared with the control subjects (n = 31), the status epilepticus groups were more likely to have an abnormal ECG with overall odds ratio of 3.8 and 7.0 for the non-epileptic and the epileptic groups respectively. Simple linear regression analysis demonstrated that children with epilepsy exhibited impaired dependence and adaptation of the QT interval on heart rate. Beat-to-beat QTc interval variability, a marker of ventricular repolarization instability, was increased in children with epilepsy. Convulsive status epilepticus can adversely affect ventricular electrical properties and stability in children

  10. Stress-induced locomotor sensitization to amphetamine in adult, but not in adolescent rats, is associated with increased expression of ΔFosB in the nucleus accumbens.

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    Paulo Eduardo Carneiro de Oliveira

    2016-09-01

    Full Text Available While clinical and pre-clinical evidence suggests that adolescence is a risk period for the development of addiction, the underlying neural mechanisms are largely unknown. Stress during adolescence has a huge influence on drug addiction. However, little is known about the mechanisms related to the interaction among stress, adolescence and addiction. Studies point to ΔFosB as a possible target for this phenomenon. In the present study, adolescent and adult rats (postnatal day 28 and 60, respectively were restrained for 2 hours once a day for 7 days. Three days after their last exposure to stress, the animals were challenged with saline or amphetamine (1.0 mg/kg i.p. and amphetamine-induced locomotion was recorded. Immediately after the behavioral tests, rats were decapitated and the nucleus accumbens was dissected to measure ΔFosB protein levels. We found that repeated restraint stress increased amphetamine-induced locomotion in both adult and adolescent rats. Furthermore, in adult rats, stress-induced locomotor sensitization was associated with increased expression of ΔFosB in the nucleus accumbens. Our data suggest that ΔFosB may be involved in some of the neuronal plasticity changes associated with stress induced-cross sensitization with amphetamine in adult rats.

  11. Arrhythmogenic right ventricular dysplasia: MRI findings

    International Nuclear Information System (INIS)

    Wall, E.E. van der; Bootsma, M.M.; Schalij, M.J.; Kayser, H.W.M.; Roos, A. de

    2000-01-01

    Arrhythmogenic right ventricular dysplasia (ARVD) is a heart muscle disorder of unknown cause that is characterized pathologically by fibrofatty replacement of the right ventricular myocardium. Clinical manifestations include structural and functional malformations of the right ventricle, electrocardiographic abnormalities, and presentation with ventricular tachycardias with left bundle branch pattern or sudden death. The disease is often familial with an autosomal inheritance. In addition to right ventricular dilatation, right ventricular aneurysms are typical deformities of ARVD and they are distributed in the so-called ''triangle of dysplasia'', i. e., right ventricular outflow tract, apex, and infundibulum. Ventricular aneurysms at these sites can be considered pathognomonic of ARVD. Another typical hallmark of ARVD is fibrofatty infiltration of the right ventricular free wall. These functional and morphologic characteristics are relevant to clinical imaging investigations such as contrast angiography, echocardiography, radionuclide angiography, ultrafast computed tomography, and magnetic resonance imaging (MRI). Among these techniques, MRI allows the clearest visualization of the heart, in particular because the right ventricle is involved, which is usually more difficult to explore with the other imaging modalities. Furthermore, MRI offers the specific advantage of visualizing adipose infiltration as a bright signal of the right ventricular myocardium. MRI provides the most important anatomic, functional, and morphologic criteria for diagnosis of ARVD within one single study. As a result, MRI appears to be the optimal imaging technique for detecting and following patients with clinical suspicion of ARVD. (orig.) [de

  12. Tolerância ao esforço em ratos com estenose aórtica e disfunção ventricular diastólica e/ou sistólica Exercise tolerance in rats with aortic stenosis and ventricular diastolic and/or systolic dysfunction

    Directory of Open Access Journals (Sweden)

    Olga Castro Mendes

    2013-01-01

    although there is no data available on this parameter in animals with ventricular dysfunction and no signs of HF. OBJECTIVE: Evaluate ST in rats with ventricular diastolic dysfunction isolated or associated with systolic dysfunction induced by ascending aortic stenosis (AoS. METHODS: Young male Wistar rats (20-30 days old, divided in: control group (CG, n=11 and AoSG group, (n=12. Animals were assessed at 6 and 18 weeks after AoS surgery. Treadmill exercise test was until exhaustion and evaluated treadmill speed and lactate concentration [LAC] at lactate threshold, treadmill speed and [LAC] at exhaustion, and total testing time. RESULTS: Echocardiography data revealed remodeling of the left atrium and left ventricular concentric hypertrophy at 6 and 18 weeks. Endocardial fractional shortening was greater in AoSG than CG at 6 and 18 weeks. Midwall fractional shortening was greater in AoSG than in CG only 6 week. Cardiac index was similar in CG and AoSG at 6 and 18 weeks and decreased between from 6 to 18 weeks in both groups. The E wave to A wave ratio was greater in CG than in AoSG at both periods and did not change in both groups between week 6 and 18. Treadmill stress testing parameters were similar in both groups at 6 or 18 weeks. CONCLUSION: Although AoS promotes isolated diastolic dysfunction or associated with systolic dysfunction at 6 or 18 weeks, it is not sufficient to modify physical stress tolerance.

  13. Lodenafil treatment in the monocrotaline model of pulmonary hypertension in rats

    OpenAIRE

    Polonio, Igor Bastos; Acencio, Milena Marques Pagliareli; Pazetti, Rogério; Almeida, Francine Maria de; Silva, Bárbara Soares da; Pereira, Karina Aparecida Bonifácio; Souza, Rogério

    2014-01-01

    We assessed the effects of lodenafil on hemodynamics and inflammation in the rat model of monocrotaline-induced pulmonary hypertension (PH). Thirty male Sprague-Dawley rats were randomly divided into three groups: control; monocrotaline (experimental model); and lodenafil (experimental model followed by lodenafil treatment, p.o., 5 mg/kg daily for 28 days) Mean pulmonary artery pressure (mPAP) was obtained by right heart catheterization. We investigated right ventricular hypertrophy (RVH) and...

  14. Hydrocephalus induces dynamic spatiotemporal regulation of aquaporin-4 expression in the rat brain

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    Praetorius Jeppe

    2010-11-01

    Full Text Available Abstract Background The water channel protein aquaporin-4 (AQP4 is reported to be of possible major importance for accessory cerebrospinal fluid (CSF circulation pathways. We hypothesized that changes in AQP4 expression in specific brain regions correspond to the severity and duration of hydrocephalus. Methods Hydrocephalus was induced in adult rats (~8 weeks by intracisternal kaolin injection and evaluated after two days, one week and two weeks. Using magnetic resonance imaging (MRI we quantified lateral ventricular volume, water diffusion and blood-brain barrier properties in hydrocephalic and control animals. The brains were analysed for AQP4 density by western blotting and localisation by immunohistochemistry. Double fluorescence labelling was used to study cell specific origin of AQP4. Results Lateral ventricular volume was significantly increased over control at all time points after induction and the periventricular apparent diffusion coefficient (ADC value significantly increased after one and two weeks of hydrocephalus. Relative AQP4 density was significantly decreased in both cortex and periventricular region after two days and normalized after one week. After two weeks, periventricular AQP4 expression was significantly increased. Relative periventricular AQP4 density was significantly correlated to lateral ventricular volume. AQP4 immunohistochemical analysis demonstrated the morphological expression pattern of AQP4 in hydrocephalus in astrocytes and ventricular ependyma. AQP4 co-localized with astrocytic glial fibrillary acidic protein (GFAP in glia limitans. In vascular structures, AQP4 co-localized to astroglia but not to microglia or endothelial cells. Conclusions AQP4 levels are significantly altered in a time and region dependent manner in kaolin-induced hydrocephalus. The presented data suggest that AQP4 could play an important neurodefensive role, and may be a promising future pharmaceutical target in hydrocephalus and CSF

  15. Anti-dopamine beta-hydroxylase immunotoxin-induced sympathectomy in adult rats

    Science.gov (United States)

    Picklo, M. J.; Wiley, R. G.; Lonce, S.; Lappi, D. A.; Robertson, D.

    1995-01-01

    Anti-dopamine beta-hydroxylase immunotoxin (DHIT) is an antibody-targeted noradrenergic lesioning tool comprised of a monoclonal antibody against the noradrenergic enzyme, dopamine beta-hydroxylase, conjugated to saporin, a ribosome-inactivating protein. Noradrenergic-neuron specificity and completeness and functionality of sympathectomy were assessed. Adult, male Sprague-Dawley rats were given 28.5, 85.7, 142 or 285 micrograms/kg DHIT i.v. Three days after injection, a 6% to 73% decrease in the neurons was found in the superior cervical ganglia of the animals. No loss of sensory, nodose and dorsal root ganglia, neurons was observed at the highest dose of DHIT. In contrast, the immunotoxin, 192-saporin (142 micrograms/kg), lesioned all three ganglia. To assess the sympathectomy, 2 wk after treatment (285 micrograms/kg), rats were anesthetized with urethane (1 g/kg) and cannulated in the femoral artery and vein. DHIT-treated animals' basal systolic blood pressure and heart rate were significantly lower than controls. Basal plasma norepinephrine levels were 41% lower in DHIT-treated animals than controls. Tyramine-stimulated release of norepinephrine in DHIT-treated rats was 27% of controls. Plasma epinephrine levels of DHIT animals were not reduced. DHIT-treated animals exhibited a 2-fold hypersensitivity to the alpha-adrenergic agonist phenylephrine. We conclude that DHIT selectively delivered saporin to noradrenergic neurons resulting in destruction of these neurons. Anti-dopamine beta-hydroxylase immunotoxin administration produces a rapid, irreversible sympathectomy.

  16. Left ventricular function in right ventricular overload

    International Nuclear Information System (INIS)

    Iwanaga, Shiro; Handa, Shunnosuke; Abe, Sumihisa; Onishi, Shohei; Nakamura, Yoshiro; Kunieda, Etsuo; Ogawa, Koichi; Kubo, Atsushi

    1989-01-01

    This study clarified regional and global functions of the distorted left ventricle due to right ventricular overload by gated radionuclide ventriculography (RNV). Cardiac catheterization and RNV were performed in 13 cases of atrial septal defect (ASD), 13 of pure mitral stenosis (MS), 10 of primary pulmonary hypertension (PPH), and 10 of normal subjects (NL). Right ventricular systolic pressure (RVSP) was 32.9±13.9, 45.0±12.2, 88.3±17.1, and 21.2±4.5 mmHg, respectively. The end-systolic LAO view of the left ventricle was halved into septal and free-wall sides. The end-diastolic halves were determined in the same plane. Ejection fractions of the global left ventricle (LVEF), global right ventricle (RVEF), the septal half of the left ventricle (SEPEF), and the free-wall half of the left ventricle (FWEF) were obtained. LVEF was 56.8±9.8% in NL, 52.8±10.5% in ASD, and 49.5±12.9% in PPH. In MS, LVEF (47.0±13.0%) was smaller than those in the other groups. RVEF was 37.0±5.2% in NL, 43.7±15.5% in ASD, and 32.8±11.5% in MS. In PPH, RVEF (25.0±10.6%) was smaller than those in the other groups. SEPEF was smaller in ASD (42.5±13.2%), MS (40.4±13.1%), PPH (40.5±12.5%) than in NL (53.5±8.5%). Systolic function of the septal half of the left ventricle was disturbed by right ventricular overload. RVEF (r=-0.35, p<0.05) and SEPEF (r=-0.51, p<0.01) had negative correlations with RVSP. As RVSP rose, systolic function of the septal half of the left ventricle was more severely disturbed. FWEF was the same among the four groups; NL (57.0±12.6%), ASD (48.6±15.2%), MS (50.5±12.0%), and PPH (51.1±12.3%). There was a good correlation between SEPEF and LVEF in NL (r=0.81), although in PPH this correlation was poor (r=0.64). These data showed that the distorted left ventricular due to right ventricular overload maintains its global function with preserved function of the free-wall side. (J.P.N.)

  17. Gestational Protein Restriction Increases Cardiac Connexin 43 mRNA levels in male adult rat offspring

    Science.gov (United States)

    Rossini, Kamila Fernanda; de Oliveira, Camila Andrea; Rebelato, Hércules Jonas; Esquisatto, Marcelo Augusto Marreto; Catisti, Rosana

    2017-01-01

    Background The dietary limitation during pregnancy influences the growth and development of the fetus and offspring and their health into adult life. The mechanisms underlying the adverse effects of gestational protein restriction (GPR) in the development of the offspring hearts are not well understood. Objectives The aim of this study was to evaluate the effects of GPR on cardiac structure in male rat offspring at day 60 after birth (d60). Methods Pregnant Wistar rats were fed a normal-protein (NP, 17% casein) or low-protein (LP, 6% casein) diet. Blood pressure (BP) values from 60-day-old male offspring were measured by an indirect tail-cuff method using an electro sphygmomanometer. Hearts (d60) were collected for assessment of connexin 43 (Cx43) mRNA expression and morphological and morphometric analysis. Results LP offspring showed no difference in body weight, although they were born lighter than NP offspring. BP levels were significantly higher in the LP group. We observed a significant increase in the area occupied by collagen fibers, a decrease in the number of cardiomyocytes by 104 µm2, and an increase in cardiomyocyte area associated with an increased Cx43 expression. Conclusion GPR changes myocardial levels of Cx43 mRNA in male young adult rats, suggesting that this mechanism aims to compensate the fibrotic process by the accumulation of collagen fibers in the heart interstitium. PMID:28678925

  18. Nitrous Oxide Induces Prominent Cell Proliferation in Adult Rat Hippocampal Dentate Gyrus

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    Farah Chamaa

    2018-05-01

    Full Text Available The identification of distinct and more efficacious antidepressant treatments is highly needed. Nitrous oxide (N2O is an N-methyl-D-aspartic acid (NMDA antagonist that has been reported to exhibit antidepressant effects in treatment-resistant depression (TRD patients. Yet, no studies have investigated the effects of sub-anesthetic dosages of N2O on hippocampal cell proliferation and neurogenesis in adult brain rats. In our study, adult male Sprague-Dawley rats were exposed to single or multiple exposures to mixtures of 70% N2O and 30% oxygen (O2. Sham groups were exposed to 30% O2 and the control groups to atmospheric air. Hippocampal cell proliferation was assessed by bromodeoxyuridine (BrdU incorporation, and BrdU-positive cells were counted in the dentate gyrus (DG using confocal microscopy. Results showed that while the rates of hippocampal cell proliferation were comparable between the N2O and sham groups at day 1, levels increased by 1.4 folds at day 7 after one session exposure to N2O. Multiple N2O exposures significantly increased the rate of hippocampal cell proliferation to two folds. Therefore, sub-anesthetic doses of N2O, similar to ketamine, increase hippocampal cell proliferation, suggesting that there will ultimately be an increase in neurogenesis. Future studies should investigate added N2O exposures and their antidepressant behavioral correlates.

  19. Repeated exposure of adult rats to transient oxidative stress induces various long-lasting alterations in cognitive and behavioral functions.

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    Yoshio Iguchi

    Full Text Available Exposure of neonates to oxidative stress may increase the risk of psychiatric disorders such as schizophrenia in adulthood. However, the effects of moderate oxidative stress on the adult brain are not completely understood. To address this issue, we systemically administrated 2-cyclohexen-1-one (CHX to adult rats to transiently reduce glutathione levels. Repeated administration of CHX did not affect the acquisition or motivation of an appetitive instrumental behavior (lever pressing rewarded by a food outcome under a progressive ratio schedule. In addition, response discrimination and reversal learning were not affected. However, acute CHX administration blunted the sensitivity of the instrumental performance to outcome devaluation, and this effect was prolonged in rats with a history of repeated CHX exposure, representing pro-depression-like phenotypes. On the other hand, repeated CHX administration reduced immobility in forced swimming tests and blunted acute cocaine-induced behaviors, implicating antidepressant-like effects. Multivariate analyses segregated a characteristic group of behavioral variables influenced by repeated CHX administration. Taken together, these findings suggest that repeated administration of CHX to adult rats did not cause a specific mental disorder, but it induced long-term alterations in behavioral and cognitive functions, possibly related to specific neural correlates.

  20. Effect of Ruta graveolens and Cannabis sativa alcoholic extract on spermatogenesis in the adult wistar male rats

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    M R Sailani

    2007-01-01

    Full Text Available Objective: The present study was undertaken to evaluate the effects of alcohol extracts of Ruta graveolens and Cannabis sativa that were used traditionally in medieval Persian medicine as male contraceptive drugs, on spermatogenesis in the adult male rats. Materials and Methods: Ethanol extracts of these plants were obtained by the maceration method. The male rats were injected intraperitionaly with C. sativa and R. graveolens 5% ethanol extracts at dose of 20 mg/day for 20 consecutive days, respectively. Twenty-four hours after the last treatment, testicular function was assessed by epididymal sperm count. Result: The statistical results showed that the ethanol extracts of these plants reduced the number of sperms significantly ( P =0.00 in the treatment groups in comparison to the control group. The results also showed that the group, treated by extract of R. graveolens reduced spermatogenesis more than the group treated by extracts of C. sativa . Conclusion: The present study demonstrated the spermatogenesis reducing properties of the ethanol extracts of R. graveolens and C. sativa in the adult male wistar rats but more studies are necessary to reveal the mechanism of action that is involved in spermatogenesis.

  1. Adolescent social instability stress increases aggression in a food competition task in adult male Long-Evans rats.

    Science.gov (United States)

    Cumming, Mark J; Thompson, Madison A; McCormick, Cheryl M

    2014-11-01

    Adolescent social instability stress (SS; daily 1 hr isolation + new cage partners postnatal days 30-45; thereafter with original cage partner, also in the SS condition) and control (CTL) rats competed for access to a preferred food in five sessions against their cage partner. In the first session, SS pairs displayed more aggression (face whacks, p = .02; rear attacks, p = .03), were less likely to relinquish access to the food voluntarily (p = .03), spent more time at the feeder than CTL pairs (p = .06), but did not differ in latency to access the feeder (p = .41). Pairs were considered in dominant-submissive relationships (DSR) if one rat spent significantly more time at the feeder than the other; 8 of 12 SS and 8 of 12 CTL pairs displayed DSRs (remaining: no-DSR). Aggression increased from the 1st to 5th session (p food reward. These results add to evidence that SS in adolescence modifies the adult social repertoire of rats and highlight the importance of adolescent social experiences for adult behavior. © 2014 Wiley Periodicals, Inc.

  2. Measurement of ventricular function using Doppler ultrasound

    International Nuclear Information System (INIS)

    Teague, S.M.

    1986-01-01

    Doppler has wide application in the evaluation of valvular heart disease. The need to know ventricular function is a much more common reason for an echocardiographic evaluation. Interestingly, Doppler examinations can assess ventricular function from many perspectives. Description of ventricular function entails measurement of the timing, rate and volume of ventricular filling and ejection. Doppler ultrasound examination reveals all of these aspects of ventricular function noninvasively, simply, and without great expense or radiation exposure, as described in this chapter

  3. Right ventricular function in patients with ischemic heart disease

    International Nuclear Information System (INIS)

    Araki, Haruo; Hisano, Ryuichi; Nagata, Yoshiyuki; Caglar, N.; Nakamura, Motoomi

    1985-01-01

    Thirty-five patients with ischemic heart disease (IHD) and 10 normal subjects were studied. Right and left ventricular ejecction fractions (EF) were determined using equilibrium radionuclide ventriculography with technetium-99m. Furthermore, abnormal motion of the right ventricular septal wall was obtained by cardiac cathetelization, and its relation to the right ventricular EF was examined. In IHD patients with anterior myocardial infarction, left ventricular EF decreased, but right ventricular EF was normal. This suggested that left ventricular dysfunction does not always have an effect on right ventricular function. Right ventricular EF was normal even when akinesis or dyskinesis was present in the ventricular septul, suggesting that abnormal motion of the ventricular septal wall has no significantly stimulant effect on right ventricular function. A decreased right ventricular EF was likely to occur only when the right ventricular free wall became ischemic or necrotic simultaneously with occurrence of posterior myocardial infarction. (Namekawa, K.)

  4. Endogenous stem cell proliferation induced by intravenous hedgehog agonist administration after contusion in the adult rat spinal cord.

    Science.gov (United States)

    Bambakidis, Nicholas C; Horn, Eric M; Nakaji, Peter; Theodore, Nicholas; Bless, Elizabeth; Dellovade, Tammy; Ma, Chiyuan; Wang, Xukui; Preul, Mark C; Coons, Stephen W; Spetzler, Robert F; Sonntag, Volker K H

    2009-02-01

    Sonic hedgehog (Shh) is a glycoprotein molecule that upregulates the transcription factor Gli1. The Shh protein plays a critical role in the proliferation of endogenous neural precursor cells when directly injected into the spinal cord after a spinal cord injury in adult rodents. Small-molecule agonists of the hedgehog (Hh) pathway were used in an attempt to reproduce these findings through intravenous administration. The expression of Gli1 was measured in rat spinal cord after the intravenous administration of an Hh agonist. Ten adult rats received a moderate contusion and were treated with either an Hh agonist (10 mg/kg, intravenously) or vehicle (5 rodents per group) 1 hour and 4 days after injury. The rats were killed 5 days postinjury. Tissue samples were immediately placed in fixative. Samples were immunohistochemically stained for neural precursor cells, and these cells were counted. Systemic dosing with an Hh agonist significantly upregulated Gli1 expression in the spinal cord (p < 0.005). After spinal contusion, animals treated with the Hh agonist had significantly more nestin-positive neural precursor cells around the rim of the lesion cavity than in vehicle-treated controls (means +/- SDs, 46.9 +/- 12.9 vs 20.9 +/- 8.3 cells/hpf, respectively, p < 0.005). There was no significant difference in the area of white matter injury between the groups. An intravenous Hh agonist at doses that upregulate spinal cord Gli1 transcription also increases the population of neural precursor cells after spinal cord injury in adult rats. These data support previous findings based on injections of Shh protein directly into the spinal cord.

  5. The value of right ventricular longitudinal strain in the evaluation of adult patients with repaired tetralogy of Fallot: a new tool for a contemporary challenge.

    Science.gov (United States)

    Almeida-Morais, Luís; Pereira-da-Silva, Tiago; Branco, Luísa; Timóteo, Ana T; Agapito, Ana; de Sousa, Lídia; Oliveira, José A; Thomas, Boban; Jalles-Tavares, Nuno; Soares, Rui; Galrinho, Ana; Cruz-Ferreira, Rui

    2017-04-01

    The role of right ventricular longitudinal strain for assessing patients with repaired tetralogy of Fallot is not fully understood. In this study, we aimed to evaluate its relation with other structural and functional parameters in these patients. Patients followed-up in a grown-up CHD unit, assessed by transthoracic echocardiography, cardiac MRI, and treadmill exercise testing, were retrospectively evaluated. Right ventricular size and function and pulmonary regurgitation severity were assessed by echocardiography and MRI. Right ventricular longitudinal strain was evaluated in the four-chamber view using the standard semiautomatic method. In total, 42 patients were included (61% male, 32±8 years). The mean right ventricular longitudinal strain was -16.2±3.7%, and the right ventricular ejection fraction, measured by MRI, was 42.9±7.2%. Longitudinal strain showed linear correlation with tricuspid annular systolic excursion (r=-0.40) and right ventricular ejection fraction (r=-0.45) (all ptetralogy of Fallot. It correlated with echocardiographic right ventricular function parameters and was independently associated with right ventricular ejection fraction derived by MRI.

  6. P-wave dispersion: relationship to left ventricular function in sickle cell anaemia.

    Science.gov (United States)

    Oguanobi, N I; Onwubere, B J; Ike, S O; Anisiuba, B C; Ejim, E C; Ibegbulam, O G

    2011-01-01

    The prognostic implications of P-wave dispersion in patients with a variety of cardiac disease conditions are increasingly being recognised. The relationship between P-wave dispersion and left ventricular function in sickle cell anaemia is unknown. This study was aimed at evaluating the relationship between P-wave dispersion and left ventricular function in adult Nigerian sickle cell anaemia patients. Between February and August 2007, a total of 62 sickle cell anaemia patients (aged 18-44 years; mean 28.27 ± 5.58) enrolled in the study. These were drawn from patients attending the adult sickle cell clinic of the University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu. An equal number of age- and gender-matched normal subjects served as controls. All the participants were evaluated with electrocardiography and echocardiography. P-wave dispersion was defined as the difference between the maximum and minimum P-wave duration measured in a 12-lead electrocardiogram. P-wave duration and P-wave dispersion were significantly higher in patients than in controls. Significant correlation was demonstrated between P-wave dispersion and age in the patients (r = 0.387; p = 0.031). A comparison of subsets of sickle cell anaemia patients and controls with comparable haematocrit values (30-35%) showed significantly higher P-wave duration and P-wave dispersion in the patients than in the controls. The P-wave duration in patients and controls, respectively, was 111.10 ± 14.53 ms and 89.14 ± 16.45 ms (t = 3.141; p = 0.006). P-wave dispersion was 64.44 ± 15.86 ms in the patients and 36.43 ± 10.35 ms in the controls (t = 2.752; p = 0.013). Significant negative correlation was found between P-wave dispersion and left ventricular transmitral E/A ratio (r = -0.289; p = 0.023). These findings suggest that P-wave dispersion could be useful in the evaluation of sickle cell patients with left ventricular diastolic dysfunction. Further prospective studies are recommended to evaluate

  7. Transient gestational and neonatal hypothyroidism-induced specific changes in androgen receptor expression in skeletal and cardiac muscles of adult rat.

    Science.gov (United States)

    Annapoorna, K; Anbalagan, J; Neelamohan, R; Vengatesh, G; Stanley, J; Amudha, G; Aruldhas, M M

    2013-03-01

    The present study aims to identify the association between androgen status and metabolic activity in skeletal and cardiac muscles of adult rats with transient gestational/neonatal-onset hypothyroidism. Pregnant and lactating rats were made hypothyroid by exposing to 0.05% methimazole in drinking water; gestational exposure was from embryonic day 9-14 (group II) or 21 (group III), lactational exposure was from postnatal day 1-14 (group IV) or 29 (group V). Serum was collected for hormone assay. Androgen receptor status, Glu-4 expression, and enzyme activities were assessed in the skeletal and cardiac muscles. Serum testosterone and estradiol levels decreased in adult rats of groups II and III, whereas testosterone remained normal but estradiol increased in group IV and V, when compared to coeval control. Androgen receptor ligand binding activity increased in both muscle phenotypes with a consistent increase in the expression level of its mRNA and protein expressions except in the forelimb of adult rats with transient hypothyroidism (group II-V). Glut-4 expression remained normal in skeletal and cardiac muscle of experimental rats. Specific activity of hexokinase and lactate dehydrogenase increased in both muscle phenotypes whereas, creatine kinase activity increased in skeletal muscles alone. It is concluded that transient gestational/lactational exposure to methimazole results in hypothyroidism during prepuberal life whereas it increases AR status and glycolytic activity in skeletal and cardiac muscles even at adulthood. Thus, the present study suggests that euthyroid status during prenatal and early postnatal life is essential to have optimal AR status and metabolic activity at adulthood. © Georg Thieme Verlag KG Stuttgart · New York.

  8. Right ventricular failure after implantation of a continuous-flow left ventricular assist device

    DEFF Research Database (Denmark)

    Cordtz, Johan Joakim; Nilsson, Jens C; Hansen, Peter B

    2014-01-01

    Right ventricular failure (RVF) is a significant complication after implantation of a left ventricular assist device. We aimed to identify haemodynamic changes in the early postoperative phase that predicted subsequent development of RVF in a cohort of HeartMate II (HMII) implanted patients....

  9. Effect of Electromagnetic Radiation Exposure on Histology and DNA Content of the Brain Cortex and Hypothalamus of Young and Adult Male Albino Rats

    International Nuclear Information System (INIS)

    Othman, A.I.; Othman, A.I.

    2012-01-01

    Concerns have been raised regarding the potential adverse effects of exposure to electromagnetic radiation (EMR) arising from mobile phone. The present study investigates the effect of the daily exposure of adult and young rats to EMR for 1 hour (at a frequency of 900 MHz, a power density of 0.02 mW/cm 2 and an average specific absorption rate of 1.165 W/kg) on the DNA content and tissue architecture of the cortex and hypothalamus of the rat brain. Both young and adult rats were sacrificed at two intervals, after 4 months of daily EMR exposure and after 1 month of stopping the exposure. The present results showed a significant increase in the DNA intensity of young and adult rats in both areas after 4 months of daily EMR exposure. However, decreased DNA content around the normal level was observed after one month of stopping the exposure. Light microscopic examination of irradiated rats revealed edema, vacuolation, necrosis and proliferated glial cells. Stopping EMR exposure showed mild amelioration in the structural damage of the cerebral cortex of young animals, however, most drastic changes still persisted in the other animals. In conclusion, these data may confirm the neurotoxic risks arising from the extensive use of mobile phones that may alter the brain histology and impair its function

  10. A exposição crônica à fumaça do cigarro resulta em remodelação cardíaca e prejuízo da função ventricular em ratos Chronic cigarette smoke exposure results in cardiac remodeling and impaired ventricular function in rats

    Directory of Open Access Journals (Sweden)

    Édson Castardeli

    2005-04-01

    Full Text Available OBJETIVO: Determinar as alterações cardíacas estruturais e funcionais causadas pela exposição à fumaça do cigarro em ratos. MÉTODOS: Os animais foram aleatoriamente distribuídos em dois grupos: fumante (F, composto por 10 animais, expostos à fumaça do cigarro, na taxa de 40 cigarros/dia e controle (C, constituído por 10 animais não submetidos à exposição. Após 4 meses, os animais foram submetidos a estudo morfológico e funcional por meio do ecocardiograma. As variáveis estudadas foram analisadas pelo teste t ou pelo teste de Mann-Whitney. RESULTADOS: Os ratos fumantes apresentaram maior átrio esquerdo (F=4,2± 0,7mm; C=3,5±0,6mm; pOBJECTIVE: To determine the cardiac structural and functional alterations caused by cigarette smoke exposure in rats. METHODS: The animals were randomly distributed into the following 2 groups: 1 smokers (S, comprising 10 animals exposed to cigarette smoke at a rate of 40 cigarettes/day; and 2 control (C, comprising 10 animals not exposed to cigarette smoke. After 4 months, the animals underwent morphological and functional study with echocardiography. The variables studied were analyzed by use of the t test or the Mann-Whitney test. RESULTS: The smoking rats had a greater left atrium (S=4.2±0.7mm; C=3.5±0.6mm; P<0.05, and greater left ventricular diastolic (S=7.9±0.7mm; C=7.2±0.5mm; P<0.05 and systolic (S=4.1±0.5; C=3.4±0.5; P<0.05 diameters. The left ventricular mass index was greater in the smoking animals (S=1.5mg/kg±0.2; C=1.3mg/kg±0.2; P<0.05, and the ejection fraction (S=0.85±0.03; C=0.89±0.03; P<0.05 and the shortening fraction (S=47.8%±3.7; C=52.7%±4.6; P<0.05 were greater in the control group. No differences were observed in the diastolic transmitral flow variables (E wave, A wave, and E/A ratio. CONCLUSION: Chronic cigarette smoke exposure results in cardiac remodeling with a decrease in ventricular functional capacity.

  11. Adiponectin protects rat myocardium against chronic intermittent hypoxia-induced injury via inhibition of endoplasmic reticulum stress.

    Directory of Open Access Journals (Sweden)

    Wenxiao Ding

    Full Text Available Obstructive sleep apnea syndrome (OSAS is associated with many cardiovascular disorders such as heart failure, hypertension, atherosclerosis, and arrhythmia and so on. Of the many associated factors, chronic intermittent hypoxia (CIH in particular is the primary player in OSAS. To assess the effects of CIH on cardiac function secondary to OSAS, we established a model to study the effects of CIH on Wistar rats. Specifically, we examined the possible underlying cellular mechanisms of hypoxic tissue damage and the possible protective role of adiponectin against hypoxic insults. In the first treatment group, rats were exposed to CIH conditions (nadir O2, 5-6% for 8 hours/day, for 5 weeks. Subsequent CIH-induced cardiac dysfunction was measured by echocardiograph. Compared with the normal control (NC group, rats in the CIH-exposed group experienced elevated levels of left ventricular end-systolic dimension and left ventricular end-systolic volume and depressed levels of left ventricular ejection fraction and left ventricular fractional shortening (p<0.05. However, when adiponectin (Ad was added in CIH + Ad group, we saw a rescue in the elevations of the aforementioned left ventricular function (p<0.05. To assess critical cardiac injury, we detected myocardial apoptosis by Terminal deoxynucleotidyl transfer-mediated dUTP nick end-labeling (TUNEL analysis. It was showed that the apoptosis percentage in CIH group (2.948% was significantly higher than that in NC group (0.4167% and CIH + Ad group (1.219% (p<0.05. Protein expressions of cleaved caspase-3, cleaved caspase-9, and cleaved-caspase-12 validated our TUNEL results (p<0.05. Mechanistically, our results demonstrated that the proteins expressed with endoplasmic reticulum stress and the expression of reactive oxygen species (ROS were significantly elevated under CIH conditions, whereas Ad supplementation partially decreased them. Overall, our results suggested that Ad augmentation could improve CIH

  12. The Role of Sulfur Dioxide in the Regulation of Mitochondrion-Related Cardiomyocyte Apoptosis in Rats with Isopropylarterenol-Induced Myocardial Injury

    Directory of Open Access Journals (Sweden)

    Junbao Du

    2013-05-01

    Full Text Available The authors investigated the regulatory effects of sulfur dioxide (SO2 on myocardial injury induced by isopropylarterenol (ISO hydrochloride and its mechanisms. Wistar rats were divided into four groups: control group, ISO group, ISO plus SO2 group, and SO2 only group. Cardiac function was measured and cardiomyocyte apoptosis was detected. Bcl-2, bax and cytochrome c (cytc expressions, and caspase-9 and caspase-3 activities in the left ventricular tissues were examined in the rats. The opening status of myocardial mitochondrial permeability transition pore (MPTP and membrane potential were analyzed. The results showed that ISO-treated rats developed heart dysfunction and cardiac injury. Furthermore, cardiomyocyte apoptosis in the left ventricular tissues was augmented, left ventricular tissue bcl-2 expression was down-regulated, bax expression was up-regulated, mitochondrial membrane potential was significantly reduced, MPTP opened, cytc release from mitochondrion into cytoplasm was significantly increased, and both caspase-9 and caspase-3 activities were increased. Administration of an SO2 donor, however, markedly improved heart function and relieved myocardial injury of the ISO-treated rats; it lessened cardiomyocyte apoptosis, up-regulated myocardial bcl-2, down-regulated bax expression, stimulated mitochondrial membrane potential, closed MPTP, and reduced cytc release as well as caspase-9 and caspase-3 activities in the left ventricular tissue. Hence, SO2 attenuated myocardial injury in association with the inhibition of apoptosis in myocardial tissues, and the bcl-2/cytc/caspase-9/caspase-3 pathway was possibly involved in this process.

  13. Histological changes in kidneys of adult rats treated with Monosodium glutamate: A light microscopic study

    Directory of Open Access Journals (Sweden)

    Singh BR, Ujwal Gajbe, Anil Kumar Reddy, Vandana Kumbhare

    2015-01-01

    Full Text Available Introduction: Monosodium Glutamate (MSG, which is chemically known as AJI-NO-MOTO also familiar as MSG in routine life. MSG is always considered to be a controversial food additive used in the world. It is a natural excitatory neurotransmitter, helps in transmitting the fast synaptic signals in one third of CNS. Liver and kidney play a crucial role in metabolism as well as elimination of MSG from the body. Present study is to detect structural changes in adult rat kidney tissue treated with MSG; observations are done with a light microscope. Materials & Methods: The study was conducted in the department of Anatomy, J.N.M.C, Sawangi (M Wardha. Thirty (30 adult Wistar rats (2-3 months old weighing about (200 ± 20g were used in the current study, animals were divided into three groups (Group – A, B, C. Group A: Control, Group B: 3 mg /gm body weight, Group C: 6 mg /gm body weight, MSG were administered orally daily for 45 days along with the regular diet. Observations & Results: The Mean values of animals weight at the end of experiment (46th day respectively were 251.2 ± 13, 244.4 ± 19.9 and 320 ± 31.1. Early degenerative changes like, Glomerular shrinkage (GSr, loss of brush border in proximal convoluted tubules and Cloudy degeneration was observed in sections of kidney treated with 3 mg/gm body weight of MSG. Animals treated with 6 mg/gm body weight of MSG showed rare changes like interstitial chronic inflammatory infiltrate with vacuolation in some of the glomeruli, and much glomerular shrinkage invaginated by fatty lobules. Conclusion: The effects of MSG on kidney tissues of adult rats revealed that the revelatory changes are directly proportional to the doses of MSG.

  14. Testosterone potentiates the hypoxic ventilatory response of adult male rats subjected to neonatal stress.

    Science.gov (United States)

    Fournier, Sébastien; Gulemetova, Roumiana; Joseph, Vincent; Kinkead, Richard

    2014-05-01

    Neonatal stress disrupts development of homeostatic systems. During adulthood, male rats subjected to neonatal maternal separation (NMS) are hypertensive and show a larger hypoxic ventilatory response (HVR), with greater respiratory instability during sleep. Neonatal stress also affects sex hormone secretion; hypoxia increases circulating testosterone of NMS (but not control) male rats. Given that these effects of NMS are not observed in females, we tested the hypothesis that testosterone elevation is necessary for the stress-related increase of the HVR in adult male rats. Pups subjected to NMS were placed in an incubator for 3 h per day from postnatal day 3 to 12. Control pups remained undisturbed. Rats were reared until adulthood, and the HVR was measured by plethysmography (fractional inspired O2 = 0.12, for 20 min). We used gonadectomy to evaluate the effects of reducing testosterone on the HVR. Gonadectomy had no effect on the HVR of control animals but reduced that of NMS animals below control levels. Immunohistochemistry was used to quantify androgen receptors in brainstem areas involved in the HVR. Androgen receptor expression was generally greater in NMS rats than in control rats; the most significant increase was noted in the caudal region of the nucleus tractus solitarii. We conclude that the abnormal regulation of testosterone is important in stress-related augmentation of the HVR. The greater number of androgen receptors within the brainstem may explain why NMS rats are more sensitive to testosterone withdrawal. Based on the similarities of the cardiorespiratory phenotype of NMS rats and patients suffering from sleep-disordered breathing, these results provide new insight into its pathophysiology, especially sex-based differences in its prevalence. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

  15. Modification of the β-Adrenoceptor Stimulation Pathway in Zucker Obese and Obese Diabetic Rat Myocardium.

    Science.gov (United States)

    Jiang, Cheng; Carillion, Aude; Na, Na; De Jong, Audrey; Feldman, Sarah; Lacorte, Jean-Marc; Bonnefont-Rousselot, Dominique; Riou, Bruno; Amour, Julien

    2015-07-01

    Although metabolic syndrome is associated with increased sympathetic activity that chronically stimulates β-adrenoceptors, the β-adrenoceptor signaling pathway has been poorly studied in this situation. We studied the β-adrenoceptor signaling pathway in Zucker lean, obese, and obese diabetic rats. Experimental, prospective study. University medical research laboratory. Adult male Zucker lean (control), obese, and obese diabetic rats. The effects of β-adrenoceptor stimulation were investigated in vitro in isolated left ventricular papillary muscles in control, obese, and obese diabetic rats. β1-, β2-, and β3-adrenoceptors and multidrug resistance-associated protein 4 were quantified by Western Blotting. Triglyceride, cholesterol, leptin, adiponectin, and C-peptide plasma concentrations were measured. Data are mean ± SD. Hyperlipidemia, high leptin, and C-peptide concentrations were observed in obese and obese diabetic strains, whereas hyperglycemia occurred only in the diabetic strain. The positive inotropic effect of isoproterenol was slightly reduced in obese rats (183% ± 11% of baseline; p = 0.003; n = 7) and markedly reduced in obese diabetic rats (137% ± 18% of baseline; p < 0.001; n = 10) when compared with control rats (210% ± 17% of baseline; n = 9). β1-adrenoceptors were down-regulated in obese (-41%; p = 0.02) and diabetic (-54%; p = 0.003) when compared with control rats, whereas β3-adrenoceptors and multidrug resistance-associated protein expression remained unchanged. Direct stimulation of adenylate cyclase with forskolin or administration of 3',5'-cyclic adenosine monophosphate suggests that subtle impairments also occurred beside the down-regulation of β1-adrenoceptor. The positive inotropic effect of β-adrenoceptor stimulation is slightly decreased in Zucker obese rats and was more markedly decreased in Zucker diabetic rats. These decreases are mainly related to β1-adrenoceptor down-regulation.

  16. Alterations in monoamines level in discrete brain regions and other peripheral tissues in young and adult male rats during experimental hyperthyroidism.

    Science.gov (United States)

    Hassan, Wafaa A; Rahman, Taghride Abdel; Aly, Mona S; Shahat, Asmaa S

    2013-08-01

    The present study was conducted to investigate the effect of experimentally-induced hyperthyroidism on dopamine (DA), norepinephrine (NE) and serotonin (5-HT) levels in different brain regions as well as in blood plasma, cardiac muscle and adrenal gland of young and adult male albino rats (60 rats of each age). Hyperthyroidism was induced by daily s.c. injection of L-thyroxine (L-T4, 500 μg/kg body wt.) for 21 consecutive days. Induction of hyperthyroidism caused a significant elevation in DA and 5-HT levels in most of the tissues studied of both young and adult animals after 7, 14, and 21 days. NE content significantly decreased after 21 days in most of the brain regions examined and after 14 and 21 days in blood plasma of young rats following hyperthyroidism. In adult rats, NE content decreased after 14 and 21 days in cardiac muscle and after 21 days only in adrenal gland. It may be suggested that the changes in monoamines level induced by hyperthyroidism may be due to disturbance in the synthesis, turnover and release of these amines through the neurons impairment or may attributed to an alteration pattern of their synthesis and/or degradative enzymes or changes in the sensitivity of their receptors. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.

  17. Ventricular fibrillation in an ambulatory patient supported by a left ventricular assist device: highlighting the ICD controversy.

    Science.gov (United States)

    Boilson, Barry A; Durham, Lucian A; Park, Soon J

    2012-01-01

    Left ventricular assist devices (LVADs) provide an effective means of managing advanced pump failure as a means of bridging to cardiac transplantation or as permanent therapy. Although ventricular arrhythmias remain common post-LVAD implantation, such therapy may allow malignant arrhythmias to be tolerated hemodynamically. This report describes the clinical findings in a patient who had likely been in a ventricular tachyarrhythmia for several days and presented in ventricular fibrillation, ambulatory, and mentating normally. This report, with previous similar reports, is additive to the body of evidence that LVADs alter the physiologic impact of ventricular arrhythmias in advanced heart failure and highlights the need for thoughtful programming of implantable cardioverter defibrillator therapies in these patients.

  18. Recurrent left ventricular myxoma presenting as cerebrovascular accidents in a teenage girl.

    Science.gov (United States)

    Vermeulen, Tom; Conraads, Viviane M; Vrints, Christiaan; Rodrigus, Inez E

    2009-12-01

    Myxoma cordis is the most frequent primary cardiac tumour in adults. Paediatric primary cardiac tumours are rare, the most common type being rhabdomyoma. Atrial and ventricular myxomas occur infrequently in the paediatric age group. Intracardiac myxomas are seen with an estimated incidence of 0.5 per million population per year. Approximately 70% of the affected patients are of female gender. Recurrences are rare (1.3%). Asymptomatic recurrences are observed in young patients who have a familial history of tumour or multifocal myxomas. Although rare, cardiac aetiology (atrial fibrillation, intracardiac thrombi, patent foramen ovale, myxoma, endocarditis) should be considered. In children presenting with central neurological symptoms, a cardiac aetiology has to be considered. We describe a rare case of an 18-year-old girl presenting with a recurrent left ventricular myxoma, accompanied by neurological deficits.

  19. Action potential conduction between a ventricular cell model and an isolated ventricular cell

    NARCIS (Netherlands)

    Wilders, R.; Kumar, R.; Joyner, R. W.; Jongsma, H. J.; Verheijck, E. E.; Golod, D.; van Ginneken, A. C.; Goolsby, W. N.

    1996-01-01

    We used the Luo and Rudy (LR) mathematical model of the guinea pig ventricular cell coupled to experimentally recorded guinea pig ventricular cells to investigate the effects of geometrical asymmetry on action potential propagation. The overall correspondence of the LR cell model with the recorded

  20. Contractilidad del músculo ventricular bajo la acción de prajmalina-propanolol y prajmalina-epinefrina Contractibility of the ventricular muscle under the action of prajmaline-propanolol and prajmaline-epinephrine

    Directory of Open Access Journals (Sweden)

    Jorge Pérez Valdivia

    2005-03-01

    Full Text Available Los efectos de la estimulación adrenérgica alfa y beta, pueden ser logrados por agentes agonistas y antagonistas, como la epinefrina y el propranolol respectivamente. Con el objetivo de precisar aspectos relacionados con la contractilidad del músculo ventricular, se realizaron un total de trece experimentos utilizando combinaciones de prajmalina-epinefrina y prajmalina-propanolol, prefundiendo preparaciones de tiras de músculo ventricular de trece ejemplares adultos de ranas catesbeiana. La prajmalina, antiarrítmico del grupo I, se obtuvo a partir de la Rauvvolfia viridis, planta endémica de Cuba. Las preparaciones fueron estimuladas con pulsos de corriente, y la tensión desarrollada por el músculo fue registrada por un transductor fuerza-desplazamiento. Las señales eléctricas fueron convertidas en trazos por un equipo registrador. Los resultados indican que las combinaciones de prajmalina-epinefrina y prajmanina-propanolol afectan de forma diametralmente opuesta la contractilidad del músculo cardíaco, aumentando en un 40% y disminuyendo en un 15% respectivamente la fuerza de la contracción del músculo ventricular. Por otra parte se sugiere un posible mecanismo de acción de la prajmalina sobre los receptores alfa presentes en las membranas de las células ventriculares.The effects of alfa and beta adrenergic stimulation can be accomplished by agonist and antagonist agents such as epinephrine and propanolol respectively. Aimed at determining the aspects related to contractibility of ventricular muscle, thirteen experiments were performed using combinations of prajmaline "epinephrine and prajmaline" propanolol, being perfused preparations of ventricular muscle strips of thirteen samples of adult Catesblian frogs. Prajmaline, a group I antiarrhythmic, was obtained from Rauvvolfia viridis, an endemic plant in Cuba. The preparations were stimulated with electric current pulses and the tension performed by the muscle was registered by a

  1. Tacrolimus-related hypertrophic cardiomyopathy in an adult cardiac transplant patient

    Institute of Scientific and Technical Information of China (English)

    LIU Tong; DONG Jian-zeng; GAO Yun; GAO Yu-long; CHENG Yu-tong; WANG Su; LI Zhi-zhong; ZHANG Hai-bo; MENG Xu; MA Chang-sheng

    2012-01-01

    Left ventricular hypertrophy associated with the use of tacrolimus is a rare complication of solid organ transplantation in adult recipients.We present a cardiac transplant recipient who developed severe concentric left ventricular hypertrophy with congestive heart failure related to myocardial hypertrophy on tacrolimus.Hypertrophy improved when the drug was discontinued and replaced with sirolimus.

  2. Moderate perinatal thyroid hormone insufficiency alters visual system function in adult rats.

    Science.gov (United States)

    Boyes, William K; Degn, Laura; George, Barbara Jane; Gilbert, Mary E

    2018-04-21

    Thyroid hormone (TH) is critical for many aspects of neurodevelopment and can be disrupted by a variety of environmental contaminants. Sensory systems, including audition and vision are vulnerable to TH insufficiencies, but little data are available on visual system development at less than severe levels of TH deprivation. The goal of the current experiments was to explore dose-response relations between graded levels of TH insufficiency during development and the visual function of adult offspring. Pregnant Long Evans rats received 0 or 3 ppm (Experiment 1), or 0, 1, 2, or 3 ppm (Experiment 2) of propylthiouracil (PTU), an inhibitor of thyroid hormone synthesis, in drinking water from gestation day (GD) 6 to postnatal day (PN) 21. Treatment with PTU caused dose-related reductions of serum T4, with recovery on termination of exposure, and euthyroidism by the time of visual function testing. Tests of retinal (electroretinograms; ERGs) and visual cortex (visual evoked potentials; VEPs) function were assessed in adult offspring. Dark-adapted ERG a-waves, reflecting rod photoreceptors, were increased in amplitude by PTU. Light-adapted green flicker ERGs, reflecting M-cone photoreceptors, were reduced by PTU exposure. UV-flicker ERGs, reflecting S-cones, were not altered. Pattern-elicited VEPs were significantly reduced by 2 and 3 ppm PTU across a range of stimulus contrast values. The slope of VEP amplitude-log contrast functions was reduced by PTU, suggesting impaired visual contrast gain. Visual contrast gain primarily reflects function of visual cortex, and is responsible for adjusting sensitivity of perceptual mechanisms in response to changing visual scenes. The results indicate that moderate levels of pre-and post-natal TH insufficiency led to alterations in visual function of adult rats, including both retinal and visual cortex sites of dysfunction. Copyright © 2018. Published by Elsevier B.V.

  3. The response of young and adult rats to the riboflavin supplementation

    Directory of Open Access Journals (Sweden)

    Camille Feitoza França

    2010-08-01

    Full Text Available The aim of this article was to study the response of young and adult rats on the supplementation of diet with riboflavin. Twenty-four young and adult normotensives (Wistar male rats, subdivided into two groups: treated (10mg riboflavin/Kg of body weight and control (receiving vehicle were daily evaluated for physical and behavioural aspects. Systolic blood pressure was determined twice a week and liver toxicity was investigated it the end of treatment. Data were evaluated using one-way ANOVA and pO processo do envelhecimento e alguns transtornos, incluindo hipertensão, foram estreitamente associados ao estresse oxidativo. Em relação à riboflavina (vitamina B2, existe uma possibilidade de que suas propriedades antioxidantes podem contribuir para controlar esse evento. Assim, esse estudo utilizou vinte e quatro ratos machos jovens e velhos normotensos (Wistar, sendo subdivididos em dois grupos: tratado (riboflavina 10 mg / kg de peso corporal e o controle (recebendo veículo. Foram avaliados diariamente aspectos físicos e comportamentais. A pressão arterial sistólica foi determinada duas vezes por semana e a toxicidade hepática foi investigada no final do tratamento. Os dados foram avaliados usando ANOVA one-way e p <0,05. A suplementação não alterou os aspectos de saúde geral dos ratos tratados, no entanto, a suplementação provocou uma significativa (p <0,05 redução da pressão arterial sistólica.

  4. Maternal periodontal disease in rats decreases insulin sensitivity and insulin signaling in adult offspring.

    Science.gov (United States)

    Shirakashi, Daisy J; Leal, Rosana P; Colombo, Natalia H; Chiba, Fernando Y; Garbin, Cléa A S; Jardim, Elerson G; Antoniali, Cristina; Sumida, Doris H

    2013-03-01

    Periodontal disease during pregnancy has been recognized as one of the causes of preterm and low-birth-weight (PLBW) babies. Several studies have demonstrated that PLBW babies are prone to developing insulin resistance as adults. Although there is controversy over the association between periodontal disease and PLBW, the phenomenon known as programming can translate any stimulus or aggression experienced during intrauterine growth into physiologic and metabolic alterations in adulthood. The purpose of the present study is to investigate whether the offspring of rats with periodontal disease develop insulin resistance in adulthood. Ten female Wistar rats were divided into periodontal disease (PED) and control (CN) groups. All rats were mated at 7 days after induction of periodontal disease. Male offspring were divided into two groups: 1) periodontal disease offspring (PEDO; n = 24); and 2) control offspring (CNO; n = 24). Offspring body weight was measured from birth until 75 days. When the offspring reached 75 days old, the following parameters were measured: 1) plasma concentrations of glucose, insulin, fructosamine, lipase, amylase, and tumor necrosis factor-α (TNF-α); 2) insulin sensitivity (IS); and 3) insulin signal transduction (IST) in insulin-sensitive tissues. Low birth weight was not detected in the PEDO group. However, plasma concentrations of glucose, insulin, fructosamine, lipase, amylase, and TNF-α were increased and IS and IST were reduced (P PEDO group compared with the CNO group. Maternal periodontal disease may induce insulin resistance and reduce IST in adult offspring, but such alterations are not attributable to low birth weight.

  5. Effects of caffeine on cortical epileptic afterdischarges in adult rats are modulated by postnatal treatment