Toll-like receptor 4 stimulation initiates an inflammatory response that decreases cardiomyocyte contractility.

Toll-like receptors (TLRs) have been identified as primary innate immune receptors for the recognition of pathogen-associated molecular patterns by immune cells, initiating a primary response toward invading pathogens and recruitment of the adaptive immune response. TLRs, especially Toll-like receptor 4 (TLR4), can also be stimulated by host-derived molecules and are expressed in the cardiovascular system, thus acting as a possible key link between cardiovascular diseases and the immune system. TLR4 is involved in the acute myocardial dysfunction caused by septic shock and myocardial ischemia.

Cardiomyocyte Toll-like receptor 4 is involved in heart dysfunction following septic shock or myocardial ischemia.

Toll-like receptors are expressed in immune cells and cardiac muscle. We examined whether the cardiac Toll-like receptor 4 (TLR4) is involved in the acute myocardial dysfunction caused by septic shock and myocardial ischemia (MI). We used wild type mice (WT), TLR4 deficient (TLR4-ko) mice and chimeras that underwent myeloablative bone marrow transplantation to dissociate between TLR4 expression in the heart (TLR4-ko/WT) and the immunohematopoietic system (WT/TLR4-ko).

Adenosine A3 receptor-mediated cardioprotection against doxorubicin-induced mitochondrial damage.

Cardiotoxicity associated with doxorubicin (DOX) treatment limits the therapeutic efficiency of this drug against cancer. 2-Chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide (Cl-IB-MECA), a selective agonist of A(3) adenosine receptor (A(3)R), reduces DOX toxicity in newborn rat cultured cardiomyocytes. The study's aim was to determine whether the protection demonstrated by Cl-IB-MECA attenuates cardiac depression in vivo.

Exogenous nitric oxide triggers classic ischemic preconditioning by preventing intracellular Ca2+ overload in cardiomyocytes.

The involvement of nitric oxide (NO) in the late phase of ischemic preconditioning is well established. However, the role of NO as a trigger or mediator of "classic preconditioning" remains to be determined. The present study was designed to investigate the effects of NO on calcium homeostasis in cultured newborn rat cardiomyocytes in normoxia and hypoxia.

Effects of menadione and its derivative on cultured cardiomyocytes with mitochondrial disorders.

Mitochondrial disorder is characteristic of many myocardial injuries such as endotoxemia, shock, acidosis, ischemia/reperfusion, and others. The goal of possible therapy is to increase ATP production. Derivatives of vitamins K may be a potent electron carrier between various mitochondrial electron-donating and electron-accepting enzyme complexes.

Analysis of calcium responses mediated by the A3 adenosine receptor in cultured newborn rat cardiac myocytes.

Intracellular calcium signaling cascade induced by adenosine A(3) receptor activation was studied in this work. It was found that adenosine A(3) receptor activation (and not A(1) or A(2A) adenosine receptors activation) leads to an increase in cytosolic calcium and its further extrusion. A selective A(3) agonist Cl-IB-MECA (2-chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide) induced an increase in cytoplasmic calcium in a dose-dependent manner, and was independent on extracellular calcium.

Detecting scaling in the period dynamics of multimodal signals: application to Parkinsonian tremor.

Patients with Parkinson's disease exhibit tremor, involuntary movement of the limbs. The frequency spectrum of tremor typically has broad peaks at "harmonic" frequencies, much like that seen in other physical processes. In general, this type of harmonic structure in the frequency domain may be due to two possible mechanisms: a nonlinear oscillation or a superposition of (multiple) independent modes of oscillation.

Correlation differences in heartbeat fluctuations during rest and exercise.

We study the heartbeat activity of healthy individuals at rest and during exercise. We focus on correlation properties of the intervals formed by successive peaks in the pulse wave and find significant scaling differences between rest and exercise. For exercise the interval series is anticorrelated at short-time scales and correlated at intermediate-time scales, while for rest we observe the opposite crossover pattern--from strong correlations in the short-time regime to weaker correlations at larger scales.

Nitric oxide is necessary for multiple memory processes after learning that a food is inedible in aplysia.

Nitric oxide (NO) signaling was inhibited via N(omega)-nitro-L-arginine methyl ester (L-NAME) during and after training Aplysia that a food is inedible. Treating animals with L-NAME 10 min before the start of training blocked the formation of three separable memory processes: (1) short-term, (2) intermediate-term, and (3) long-term memory. The treatment also attenuated, but did not block, a fourth memory process, very short-term memory.

Cardiomyocyte resistance to doxorubicin mediated by A(3) adenosine receptor.

Recently, we reported that the activation of A(3) adenosine receptor (A(3)R) in newborn cultured cardiomyocytes by highly selective agonist Cl-IB-MECA (2-chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide) induces protection against the anthracycline antibiotic doxorubicin (DOX) cardiotoxicity. The present study was undertaken to further characterize the cardioprotective action of A(3)R activation by revealing the structural changes in cardiomyocytes elicited upon exposure to DOX. Morphological observations (ultrastructural and immunocytochemical) indicate that after DOX treatment, the cardiomyocytes undergo destructive alterations, and protective action of A(3)R is not connected with its anti-apoptotic activity.

Mechanisms underlying fictive feeding in aplysia: coupling between a large neuron with plateau potentials activity and a spiking neuron.

The buccal ganglia of Aplysia contain a central pattern generator (CPG) that organizes the rhythmic movements of the radula and buccal mass during feeding. Many of the cellular and synaptic elements of this CPG have been identified and characterized. However, the roles that specific cellular and synaptic properties play in generating patterns of activity are not well understood.

Activation of A(3)adenosine receptor protects against doxorubicin-induced cardiotoxicity.

Adenosine exerts a marked protective effect on the heart during cardiac ischemia. This protection is mediated by binding to the A(1)and A(3)subtypes of adenosine receptor (A(1)R and A(3)R, respectively). The objective of the present study was to investigate whether activation of A(1)and A(3)adenosine receptors may reduce doxorubicin-induced damage to cardiomyocytes in culture.

Increased cardiac alpha-1-adrenoceptor density in rats following treatment with amiodarone.

This study was undertaken to investigate the interaction between amiodarone and alpha-1-adrenoceptors in rat cardiac cells. The level (Bmax) and affinity (Kd) of alpha-1-adrenoceptors in heart cells were determined by [3H]prazosin radioligand binding following amiodarone treatment. In cultured intact cardiocytes treated for 48 h with 10 microM amiodarone, [3H]prazosin binding increased by 31% compared with the control cells (p<0.

Cardioprotective effects of adenosine A1 and A3 receptor activation during hypoxia in isolated rat cardiac myocytes.

Adenosine (ADO) is a well-known regulator of a variety of physiological functions in the heart. In stress conditions, like hypoxia or ischemia, the concentration of adenosine in the extracellular fluid rises dramatically, mainly through the breakdown of ATP. The degradation of adenosine in the ischemic myocytes induced damage in these cells, but it may simultaneously exert protective effects in the heart by activation of the adenosine receptors.

Induction of apoptosis in rat cardiocytes by A3 adenosine receptor activation and its suppression by isoproterenol.

The purpose of the present study was to investigate the mechanisms involved in the induction of apoptosis in newborn cultured cardiomyocytes by activation of adenosine (ADO) A3 receptors and to examine the protective effects of beta-adrenoceptors. The selective agonist for A3 ADO receptors Cl-IB-MECA (2-chloro-N6-iodobenzyl-5-N-methylcarboxamidoadenosine) and the antagonist MRS1523 (5-propyl-2-ethyl-4-propyl-3-(ethylsulfanylcarbonyl)-6-phenylpy rid ine-5-carboxylate) were used. High concentrations of the Cl-IB-MECA (> or = 10 microM) agonist induced morphological modifications of myogenic cells, such as rounding and retraction of cell body and dissolution of contractile filaments, followed by apoptotic death.

Uptake of glucose analogs reflects the rate of contraction of cultured myocytes.

The present study demonstrates that: a) adenosine and R-N6-(2-phenylisopropyl)-adenosine (R-PIA, A1 and A3 adenosine receptor agonist) inhibited [3H]deoxyglucose uptake or [3H]3-O-methyl-D-glucose uptake; b) sugar uptake reflects the rate of contraction in cardiac cultures; c) [3H]deoxyglucose uptake or [3H]3-O-methyl-D-glucose uptake are useful quantitative probes for beating rate evaluation. A 25-40% decrease in [3H]deoxyglucose uptake (p < 0.01) was obtained following 13-21 min treatment with 100 microM adenosine together with 1 microM dipyridamole or with 10 microM R-PIA, which inhibited spontaneous contractions.

Separate effects of a classical conditioning procedure on respiratory pumping, swimming, and inking in Aplysia fasciata.

We examined whether swimming and inking, two defensive responses in Aplysia fasciata, are facilitated by a classical conditioning procedure that has been shown to facilitate a third defensive response, respiratory pumping. Training consisted of pairing a head shock (UCS) with a modified seawater (85%, 120%, or pH 7.0 seawater--CSs).