Urotensin II-Induced Increase in Myocardial Distensibility Is Modulated by Angiotensin II and Endothelin-1

Endogenous regulators, such as angiotensin-II (AngII), endothelin-1 (ET-1) and urotensin-II (U-II) are released from various cell types and their plasma levels are elevated in several cardiovascular diseases. The present study evaluated a potential crosstalk between these systems by investigating if the myocardial effects of U-II are modulated by AngII or ET-1. Effects of U-II (10(-8), 10(-7), 10(-6) M) were tested in rabbit papillary muscles in the absence and in the presence of losartan (selective AT, receptor antagonist), PD-145065 (nonselective ET-1 receptors antagonist), losartan plus PD-145065, AngII or ET-1. U-II promoted concentration-dependent negative inotropic and lusitropic effects that were abolished in all experimental conditions. Also, U-II increased resting muscle length up to 1.008 +/- 0.002 L/L(max). Correcting it to its initial value resulted in a 19.5 +/- 3.5 % decrease of resting tension, indicating increased muscle distensibility. This effect on muscle length was completely abolished in the presence of losartan and significantly attenuated by PD-145065 or losartan plus PD-145065. This effect was increased in the presence of AngII, resulting in a 27.5 +/- 3.9 % decrease of resting tension, but was unaffected by the presence of ET-1. This study demonstrated an interaction of the U-II system with the AngII and ET-1 systems in terms of regulation of systolic and diastolic function

Modulation of Myocardial Stiffness by beta-Adrenergic Stimulation Its Role in Normal and Failing Heart

The acute effects of ß-adrenergic stimulation on myocardial stiffness were evaluated. New-Zealand white rabbits were treated with saline (control group) or doxorubicin to induce heart failure (HF) (DOXO-HF group). Effects of isoprenaline (10 -10-1 -5 M), a non-selective ß-adrenergic agonist, were tested in papillary muscles from both groups. In the control group, the effects of isoprenaline were also evaluated in the presence of a damaged endocardial endothelium, atenolol (ßi-adrenoceptor antagonist), ICI-118551 (ßz-adrenoceptor antagonist), KT-5720 (PKA inhibitor), L-NNA (NO-synthase inhibitor), or indomethacin (cyclooxygenase inhibitor). Passive length-tension relations were constructed before and after adding isoprenaline (10 -5 M). In the control group, isoprenaline increased resting muscle length up to 1.017±0.006 L/L max. Correction of resting muscle length to its initial value resulted in a 28.5±3.1% decrease of resting tension, indicating decreased muscle stiffness, as confirmed by the isoprenaline-induced right-downward shift of the passive lengthtension relation. These effects were modulated by ßr and ß 2adrenoceptors and PKA. In DOXO-HF group, the effect on myocardial stiffness was significantly decreased. We conclude that ß-adrenergic stimulation is a relevant mechanism of acute neurohumoral modulation of the diastolic function. Furthermore, this study clarifies the mechanisms by which myocardial stiffness is decreased. (c) 2011 Institute of Physiology v.v.i., Academy of Sciences of the Czech Republic, Prague, Czech Republic

Echocardiographic evaluation including tissue Doppler imaging in New Zealand white rabbits sedated with ketamine and midazolam

Limited data are available on the use of more recent echocardiographic parameters in the rabbit. Echocardiographic examination, including conventional echocardiography and tissue Doppler imaging (TDI), was performed on 26 male New Zealand white rabbits under ketamine-midazolam sedation. Particular emphasis was placed on the more recent systolic and diastolic parameters, such as myocardial performance index (Tei index) and mitral annular motion (from septal and lateral sides of the left ventricle) obtained using pulsed TDI. Parameters that assessed systolic and diastolic function (fractional shortening, Tei index, and maximal mitral E- and A-wave velocities) were comparable to those reported in the literature for rabbits in the awake state. The less cardiodepressive anaesthetic protocol could offer a good alternative in performing echocardiographic evaluation whenever such caution is necessary. TDI is feasible in healthy rabbits and potentially suitable for the investigation of left ventricle systolic and diastolic function

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

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

Five-Year Outcome in Stroke Patients Submitted to Thrombolysis

BACKGROUND AND PURPOSE: Little is known on long-term follow-up after thrombolysis in ischemic stroke patients because the majority of studies evaluated outcome at 3 to 12 months. We aimed to assess 5-year outcome after intravenous thrombolysis (IVT). METHODS: Cohort study based on the prospective registry of all consecutive ischemic stroke patients submitted to IVT in our Stroke Unit. Five-year outcome, including living settings, functional outcome, stroke recurrence, and mortality, was ascertained by telephonic interviews and additional review of clinical records. Multivariate analyses were performed to identify predictors of outcome and mortality. Excellent outcome was defined as modified Rankin scale 0 to 1. RESULTS: Five-year outcome was available for 155/164 patients submitted to IVT. At 5 years, 32.9% of patients had an excellent outcome (95% confidence interval (CI) =25.5-43.3) and mortality was 43.9% (95%CI=36.1-51.7). Increasing age (odds ratio =0.93, 95% CI =0.90-0.97) and increasing National Institute of Health Stroke Scale (NIHSS) 24 h after thrombolysis (odds ratio =0.81, 95% CI =0.74-0.90) were independently associated with a lower likelihood of an excellent 5-year outcome. Age (hazards ratio =1.07, 95% CI =1.03-1.11) and excellent functional outcome 3 months after thrombolysis (hazards ratio =0.28, 95%CI=0.12-0.66) were independently associated with mortality during follow-up. CONCLUSIONS: One third of ischemic stroke patients have excellent 5-year outcome after IVT. Younger age, lower NIHSS 24 h after IVT, and excellent 3-month functional outcome are independent predictors of excellent 5-year outcome

Negative inotropic effect of selective AT(2) receptor stimulation and its modulation by the endocardial endothelium

Angiotensin II is an octapeptide whose effects are mediated by two types of receptors. AT, receptors are responsible for the vasoconstrictor, positive inotropic and growth promoting properties, while AT(2) receptors have been linked to vasodilator and anti-mitogenic properties. In this study we investigated the effects of selective AT, receptor stimulation on myocardial contractility and lusitropy. Effects of selective AT2 receptor activation were evaluated in rabbit right papillary muscles (n=96) by adding increasing concentrations of H-9395, an AT(2) receptor agonist, alone or in presence of a selective AT, receptor antagonist (ZD-7155), or alternatively, by adding increasing concentrations of angiotensin 11 in presence of ZD-7155. In the latter conditions, selective AT2 receptor activation was also performed in presence of NG-nitro-L-Arginine, indomethacin, proadifen, hydroxocobalamin, apamin plus charybdotoxin, Hoe-140 or PD-123,319, as well as, after endocardial endothelium removal. Selective AT2 stimulation induced a negative inotropic and lusitropic effect in the first three protocols. This effect was completely abolished after selective removal of the endocardial endothelium and blunted in presence of Hoe-140, hydroxocobalamin, apamin plus charybdotoxin and PD-123,319, but maintained in presence of NG-nitro-L-Arginine, indomethacin or proadifen. Selective AT(2) receptor stimulation induces a negative inotropic and lusitropic effect, which is modulated by endocardial endothelium, and mediated by bradykinin B, receptors through NO release and calcium dependent potassium channels activation. Such findings may help to better understand the therapeutic effects of selective AT, antagonists, which are increasingly used for treating cardiovascular diseases. (C) 2007 Published by Elsevier B.V

Numerical study of circulation on the inner Amazon Shelf

Author Posting. © Springer, 2008. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Ocean Dynamics 58 (2008): 187-198, doi:10.1007/s10236-008-0139-4.We studied the circulation on the coastal domain of the Amazon Shelf by applying the hydrodynamic module of the Estuarine and Coastal Ocean Model and Sediment Transport - ECOMSED. The first barotropic experiment aimed to explain the major bathymetric effects on tides and those generated by anisotropy in sediment distribution. We analyzed the continental shelf response of barotropic tides under realistic bottom stress parametrization (Cd), considering sediment granulometry obtained from a faciologic map, where river mud deposits and reworked sediments areas are well distinguished, among others classes of sediments. Very low Cd values were set in the fluid mud regions off the Amapa coast (1.0 10-4 ), in contrast to values around 3:5 10-3 for coarser sediment regions off the Para coast. Three-dimensional experiments represented the Amazon River discharge and trade winds, combined to barotropic tide influences and induced vertical mixing. The quasi-resonant response of the Amazon Shelf to the M2 tide act on the local hydrodynamics by increasing tidal admittance, along with tidal forcing at the shelf break and extensive fluid mud regions. Harmonic analysis of modeled currents agreed well with analysis of the AMASSEDS observational data set. Tidal-induced vertical shear provided strong homogenization of threshold waters, which are subject to a kind of hydraulic control due to the topographic steepness. Ahead of the hydraulic jump, the low-salinity plume is disconnected from the bottom and acquires negative vorticity, turning southeastward. Tides act as a generator mechanism and topography, via hydraulic control, as a maintainer mechanism for the low-salinity frontal zone positioning. Tidally induced southeastward plume fate is overwhelmed by northwestward trade winds so that, along with background circulation, probably play the most important role on the plume fate and variability over the Amazon Shelf

Neuregulin1/ErbB system: importance in the control of cardiovascular function

The family of Neuregulins (NRG), growth factors like epidermal growth factor, is known to induce growth and differentiation of epithelial, glial, neuronal, and skeletal muscle cells. This family comprises four members, being NRG1 the most largely studied, particularly at the cardiovascular level. The biological effects of NRG1 in the adult heart are mediated by the tyrosine kinase receptors ErbB. In the adult heart, NRG1 is expressed by cells of the endocardial endothelium and the cardiac microvascular endothelium, and the receptors ErbB2/ErbB4 are expressed by ventricular cardiomyocytes and are located in T-tubule system and intercalated disks in close proximity to the system components of excitation-contraction coupling. The importance of the NRG/ErbB signaling axis at the cardiovascular level became evident after discovering that patients treated with trastuzumab (inhibitory antibody against ErbB2, used in the treatment of breast cancer) can develop ventricular dysfunction and have higher risk of cardiomyopathy when co-administered with anthracyclines. Subsequent studies in vitro and in vivo have clarified the effects and the respective signaling pathways associated with the NRG/ErbB system in the adult heart. Some cardiovascular functions of the NRG1/ErbB system have been described at the vascular (stimulation of angiogenesis and ateroprotector effect) and myocardium level (negative inotropic effect) as well as effect on the survival, cell growth and organization of the cardiomyocytes (myofibrillar organization and cell-to-cell contact between cardiomyocytes). Furthermore, the interaction of this system with other neurohumoral mediators has been studied. Thus, there seems to be a physiological role in modulating the sympathovagal balance and an interaction with endothelin-1 signaling. All these effects result from the activation of different intracellular signaling cascades, as a consequence of the binding of NRG1 to ErbB receptors. Some cardiac signaling pathways identified until now include molecules such as MEK / Erk 1/2, phosphatidylinositol 3-kinase/ Akt, focal adhesion kinase, Gab (Grb-2-associated binder) family, vascular endothelial growth factor and NO production by endothelial nitric oxide synthase. Thus, the aim of this paper was to make an up-to-date review of existing information on NRG1/ErbB signaling axis, with particular focus on its cardiovascular effects

Regulated Nuclear Trafficking of rpL10A Mediated by NIK1 Represents a Defense Strategy of Plant Cells against Virus

The NSP-interacting kinase (NIK) receptor-mediated defense pathway has been identified recently as a virulence target of the geminivirus nuclear shuttle protein (NSP). However, the NIK1–NSP interaction does not fit into the elicitor–receptor model of resistance, and hence the molecular mechanism that links this antiviral response to receptor activation remains obscure. Here, we identified a ribosomal protein, rpL10A, as a specific partner and substrate of NIK1 that functions as an immediate downstream effector of NIK1-mediated response. Phosphorylation of cytosolic rpL10A by NIK1 redirects the protein to the nucleus where it may act to modulate viral infection. While ectopic expression of normal NIK1 or a hyperactive NIK1 mutant promotes the accumulation of phosphorylated rpL10A within the nuclei, an inactive NIK1 mutant fails to redirect the protein to the nuclei of co-transfected cells. Likewise, a mutant rpL10A defective for NIK1 phosphorylation is not redirected to the nucleus. Furthermore, loss of rpL10A function enhances susceptibility to geminivirus infection, resembling the phenotype of nik1 null alleles. We also provide evidence that geminivirus infection directly interferes with NIK1-mediated nuclear relocalization of rpL10A as a counterdefensive measure. However, the NIK1-mediated defense signaling neither activates RNA silencing nor promotes a hypersensitive response but inhibits plant growth and development. Although the virulence function of the particular geminivirus NSP studied here overcomes this layer of defense in Arabidopsis, the NIK1-mediated signaling response may be involved in restricting the host range of other viruses

Application of Chinese Jun-Cao technique for the production of Brazilian Ganoderma lucidum strains

Ganoderma lucidum is a medicinal mushroom traditionally used in China against a wide range of diseases such as cancer and also for its prevention. In this work, commercial Chinese strains G. lucidum were compared to wild Brazilian strains aiming to determine the cultivation potential through the use of Jun-Cao. Six formulations were tested and the strains presented good response to the applied method. In general, the mixture between the grass and wood was well suited for the basidiomycetes, contributing to the preparation of substrates that generated better results in Jun Cao