1,720,984 research outputs found
Cardioprotection by ouabain and digoxin in perfused rat hearts
No full textThis work was aimed at determining the cardioprotective effect of digitalis glycosides in rat heart, and to relate it with Na+, K+-ATPase inhibition and ERK1/2 activation. Isolated working rat hearts were perfused in the presence of ouabain or digoxin, which were used at concentrations ranging from 10(-8) to 10(-5) M. The hearts were then subjected to 30 minutes of global normothermic ischemia followed by 120 minutes of retrograde reperfusion; irreversible tissue injury was determined on the basis of triphenyltetrazolium chloride staining. Significant cardioprotection was observed with 10(-7) M and 10(-5) M ouabain (ischemic injury averaged 7.0 +/- 3.5% and 8.3 +/- 0.6% versus 37.3 +/- 2.0% in controls. P < 0.01 in each case). Hearts treated with digoxin showed decreased ischemic injury at 10(-6) M and 10(-5) M (18.0 +/- 1.5% and 14.2 +/- 1.0%, P < 0.01 versus control in both cases). In parallel experiments, ERK2 phosphorylation was increased by 10(-7) to 10(-5) M ouabain, while ERK1 and ERK2 phosphorylation was increased by 10(-6) to 10(-5) M digoxin. The cardioprotective effect was not related to Na+, K+-ATPase inhibition, since Rb+ uptake was not significantly different between control and treated hearts
Production of ouabain-like factor in normal and ischemic rat heart
No full textEndogenous ouabain-like factor (OLF) has been detected in mammalian plasma, adrenal gland, and hypothalamus. We investigate whether cardiac tissue may also produce OLF. HPLC chromatographic separation of cardiac extracts showed that RIA-determined OLF activity coincided with the elution profile of exogenous ouabain and with the ability to inhibit 86Rb uptake in human erythrocytes. OLF activity was remarkably higher in excised hearts (3.94 +/- 0.84 pmol/g wet weight by RIA) than in rat blood (0.05 +/- 0.02 pmol/ml). Similar values were obtained in perfused working hearts, without significant changes over time from 5 to 30 minutes of aerobic perfusion. Significant OLF release in the perfusion buffer was also observed (0.54 +/- 0.05 pmoles over 30 minutes). In hearts subjected to 15 minutes of aerobic perfusion followed by 15 minutes of global myocardial ischemia OLF concentration was remarkably increased (8.59 +/- 1.13 versus 4.58 +/- 0.57 pmol/g wet weight by RIA, P < 0.01; an increase after ischemia was confirmed by the assay of 86Rb uptake). Our findings suggest that the rat heart is able to produce OLF, and that its concentration increases during ischemia. Myocardial OLF might modulate the Na/K-ATPase, producing relevant effects on ionic homeostasis and/or gene transcription
The role of tandem mass spectrometry in clinical chemistry: quantification of steroid hormones and vitamin D
No full textNowadays tandem mass spectrometry coupled to liquid chromatography is considered as the "gold standard" technique for steroid hormones quantification in biological fluids. Its emerging role in the clinical laboratories is mainly due to its capability to overcome the main limitations of the widespread immunoassays (IAs), providing, at the same time, the simultaneous quantification of several steroids of interest. This is a very important feature, as it allows, just in a single analysis, the monitoring of some key steroids in a metabolic pathway. In this chapter, we will describe the instrumental layout to be used in the measurement of clinically relevant steroids or steroid panels, and we will discuss the advantages and disadvantages of tandem mass spectrometry with respect to the main IA-based assays. The quantification of the main metabolites of vitamin D, 25-hydroxyvitamin D3, which is considered a steroid hormone, is also discussed in the chapter. Applications concerning 11β-HSD enzyme activity, 21-hydroxylase deficiency in newborns, hypovitaminosis D in patients with heart failure and vitamin D intoxication are discussed
LTI Models for 3-Iodothyronamine Time Dynamics: A Multiscale View.
No full text3-Iodothyronamine (T1AM) is a novel relative of
thyroid hormone that plays a role in critical body regulatory
processes, such as glucose metabolism, thermal regulation and
heart beating. This work was aimed at characterizing time
dynamics of T1AM and its catabolite 3-iodothyroacetic acid
(TA1) in different biological scales with LTI (Linear Time
Invariant) models. Culture medium samples coming from
culture of H9c2 murine cells and perfusion liquid samples from
perfused rat heart were collected after the injection of a T1AM
bolus. T1AM and TA1 concentrations in the samples were
assayed with high performance liquid chromatography
coupled to tandem mass spectrometry. Kinetic constants
relative to T1AM transport and conversion were estimated
with Weighted Least Squares method. We found that these
constants can be related with an allometric power law
depending on mass, with a negative exponent of -0.27± 0.19,
implying that the velocity of conversion and internalization of
T1AM decrease with increasing of system mass
Ca2+ channel remodelling in perfused heart: effects of mechanical work and interventations affecting Ca2+ cycling on sarcolemmal and sarcoplasmic reticulum Ca2+ channels
No full text
Preconditioning by adenosine is associated with increased sarcoplasmic reticulum phospholamban expression
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