Regulation of Papillary Muscle Contractility by NAD and Ammonia Interplay: Contribution of Ion Channels and Exchangers.

Various models, including stem cells derived and isolated cardiomyocytes with overexpressed channels, are utilized to analyze the functional interplay of diverse ion currents involved in cardiac automaticity and excitation-contraction coupling control. Here, we used β-NAD and ammonia, known hyperpolarizing and depolarizing agents, respectively, and applied inhibitory analysis to reveal the interplay of several ion channels implicated in rat papillary muscle contractility control. We demonstrated that: 4 mM β-NAD, having no strong impact on resting membrane potential (RMP) and action potential duration (APD90) of ventricular cardiomyocytes, evoked significant suppression of isometric force (F) of paced papillary muscle.

[ABNORMAL UTERINE BLEEDING IN ADOLESCENT GIRLS: HEREDITARY AND ENVIRONMENTAL RISK FACTORSS].

The objective of this work was to identify prognostic factors of the environment and heredity in the families of girls with abnormal uterine bleeding during puberty. Clinical and genealogical analysis has been carried out according to P. Harper in the families of 70 girls with abnormal uterine bleeding (AUB) during puberty.

Deregulation of Ca-Signaling Systems in White Adipocytes, Manifested as the Loss of Rhythmic Activity, Underlies the Development of Multiple Hormonal Resistance at Obesity and Type 2 Diabetes.

Various types of cells demonstrate ubiquitous rhythmicity registered as simple and complex Ca-oscillations, spikes, waves, and triggering phenomena mediated by G-protein and tyrosine kinase coupled receptors. Phospholipase C/IP-receptors (PLC/IPR) and endothelial NO-synthase/Ryanodine receptors (NOS/RyR)-dependent Ca signaling systems, organized as multivariate positive feedback generators (PLC-G and NOS-G), underlie this rhythmicity. Loss of rhythmicity at obesity may indicate deregulation of these signaling systems.

[PHYSICAL DEVELOPMENT AS A KEY TO THE SUCCESS OF THE FORMATION OF REPRODUCTIVE POTENTIAL].

The aim of this study was to analyze the characteristics of physical and sexual development of patients with menstrual irregularities while monitoring over the past 20 years. Physical and sexual development of 497 patients with abnormal uterine bleeding (AMC PP) and 677 with hypomenstrual syndrome (HMS) aged 10 to 18 years were evaluated who were treated in the period 1997-2002 and 2010-2016. The data were compared with the results of epidemiological studies of a population of schoolgirls in Kharkov region.

Dissecting Cellular Mechanisms of Long-Chain Acylcarnitines-Driven Cardiotoxicity: Disturbance of Calcium Homeostasis, Activation of Ca-Dependent Phospholipases, and Mitochondrial Energetics Collapse.

Long-chain acylcarnitines (LCAC) are implicated in ischemia-reperfusion (I/R)-induced myocardial injury and mitochondrial dysfunction. Yet, molecular mechanisms underlying involvement of LCAC in cardiac injury are not sufficiently studied. It is known that in cardiomyocytes, palmitoylcarnitine (PC) can induce cytosolic Ca accumulation, implicating L-type calcium channels, Na/Ca exchanger, and Ca-release from sarcoplasmic reticulum (SR).

The mitochondrial NO-synthase/guanylate cyclase/protein kinase G signaling system underpins the dual effects of nitric oxide on mitochondrial respiration and opening of the permeability transition pore.

The available data on the involvement of nitric oxide (NO) and mitochondrial calcium-dependent NO synthase (mtNOS) in the control of mitochondrial respiration and the permeability transition pore (mPTP) are contradictory. We have proposed that the mitochondrial mtNOS/guanylate cyclase/protein kinase G signaling system (mtNOS-SS) is also implicated in the control of respiration and mPTP, providing the interplay between NO and mtNOS-SS, which, in turn, may result in inconsistent effects of NO. Therefore, using rat liver mitochondria, we applied specific inhibitors of the enzymes of this signaling system to evaluate its role in the control of respiration and mPTP opening.

Angiotensin II activates different calcium signaling pathways in adipocytes.

Angiotensin II (Ang II) is an important mammalian neurohormone involved in reninangiotensin system. Ang II is produced both constitutively and locally by RAS systems, including white fat adipocytes. The influence of Ang II on adipocytes is complex, affecting different systems of signal transduction from early Са(2+) responses to cell proliferation and differentiation, triglyceride accumulation, expression of adipokine-encoding genes and adipokine secretion.

To Break or to Brake Neuronal Network Accelerated by Ammonium Ions?

Purpose: The aim of present study was to investigate the effects of ammonium ions on in vitro neuronal network activity and to search alternative methods of acute ammonia neurotoxicity prevention.

Methods: Rat hippocampal neuronal and astrocytes co-cultures in vitro, fluorescent microscopy and perforated patch clamp were used to monitor the changes in intracellular Ca2+- and membrane potential produced by ammonium ions and various modulators in the cells implicated in neural networks.

Results: Low concentrations of NH4Cl (0.

Acetylcholine promotes Ca2+ and NO-oscillations in adipocytes implicating Ca2+→NO→cGMP→cADP-ribose→Ca2+ positive feedback loop--modulatory effects of norepinephrine and atrial natriuretic peptide.

Purpose: This study investigated possible mechanisms of autoregulation of Ca(2+) signalling pathways in adipocytes responsible for Ca(2+) and NO oscillations and switching phenomena promoted by acetylcholine (ACh), norepinephrine (NE) and atrial natriuretic peptide (ANP).

Methods: Fluorescent microscopy was used to detect changes in Ca(2+) and NO in cultures of rodent white adipocytes. Agonists and inhibitors were applied to characterize the involvement of various enzymes and Ca(2+)-channels in Ca(2+) signalling pathways.

[Alpha-adrenergic regulation of two calcium signal pathways in adipocytes].

Using selective receptor's agonist and antagonists we show that mouse white fat cells express alpha1A-, alpha2-adrenergic receptors, which activation with noradrenaline is capable of causing calcium responses different by formation mechanism. Adipocyte's calcium responses to alpha1-adrenoreceptor agonists are caused by alpha1A-type adrenoreceptor and suppressed by inhibitors of PLC-dependent pathway. Calcium responses to alpha2-adrenoreceptors agonists are realized only in the presence of more than 200 microM of L-arginine and suppressed by inhibitors of NOS-PKG-RyR pathway.

[Destabilization of the cytosolic calcium level and cardiomyocyte death in the presence of long-chain fatty acid derivatives].

It has been shown using the fluorescent microscopy technique that long-chain fatty acid derivatives, myristoylcarnitine and palmitoylcarnitine, exert the most toxic effect on rat ventricular cardiomyoctes. The addition of 20-50 microM acylcarnitines increases calcium concentration in cytoplasm ([Ca2+]i) and causes cell death after the 4-8 min lag-period. This effect is independent on extracellular calcium and L-type calcium channel inhibitors.

[Classification of pneumoconiosis].

The article presents a modern classification of pneumoconiosis taking account of the international classification and experience gained by specialists in this country.

Stoichiometric traps in the tricarboxylic acid cycle. I. Self-inhibition and triggering phenomena.

The steady-state oxidation of 2 mM pyruvate in pigeon and rat heart mitochondria in the presence of ADP-glucose-hexokinase load can be strongly inhibited by excess (10-40 mM) of pyruvate or beta-hydroxybutyrate. This inhibition is accompanied by the accumulation of alpha-ketoglutarate and a decrease of malate. The mechanism of such substrate inhibition may be associated with the limitation of the tricarboxylic acid cycle flux by low levels of oxaloacetate and free CoA due to their being trapped as alpha-ketoglutarate and acetyl-CoA.

Regulation of the tricarboxylic acid cycle and beta-oxidation by excess substrates.

A simple mathematical model is proposed to explain the inhibition of beta-oxidation and of the tricarboxylic acid cycle by excess of fatty acids. This model is based on the peculiar stoichiometry of beta-oxidation reactions, which accounts for the formation of dynamical traps for free CoA and its esters in the form of 3-ketoacyl-CoA derivatives. It follows from the analysis of the model that the fatty acids can produce 100% inhibition of respiration at some critical concentrations depending on their chain lengths.

[Substrate inhibition in the tricarboxylic acid cycle].

It has been shown in the experiments on rat liver mitochondria under glucose hexo-kinase load that excess of substrates of (1-20 mM) pyruvate, acetate, propionate, pent-4-enoate and malate may induce oxidation of NAD(P)H and inhibition of mitochondrial respiration (by 20-50% and more) due to a decreased rate of hydrogen production by tricarboxylic acid cycle. It has been concluded from the analysis of mathematical models and metabolite-testings which remove this inhibition that for pyruvate and acetate this inhibition is an autocatalytic one. It is related to a decreased level of CoA and oxaloacetate due to the formation of "traps" such as acetyl-CoA and alpha-kotoglutarate.

[Mechanisms of the regulation of muscle energy metabolism on oxidation of glucose and fatty acids. A mathematical model].

A mathematical model was used to study the role of various allosteric regulatory mechanisms in the oxidation of glucose and fatty acids by muscle energy metabolism. A large number of such mechanisms were shown to be involved in simultaneous oxidation of both substrates: glycolysis is regulated by the ATP/ADP ratio at the phosphofructokinase (PFK) step; the control over pyruvate dehydrogenase is exercised by the NADHm/NADm+ and CoAsAc/CoAsH ratios as well as by the level of pyruvate; the Krebs cycle is regulated by oxaloacetate and citrate concentrations in the citrate synthase reaction and by the ATP/ADP and NADHm/NADm+ ratios in the isocitrate dehydrogenase reaction. The inhibition of PFK and pyruvate dehydrogenase by excess of CoAsAcyl as well as the inhibition of PFK by citrate are additional equivalent regulatory mechanisms.

[Mechano-metabolic coupling in the myocardium in response to electric stimulation].

Fluorescent and mechanical responses to a series of electrical impulses of papillary muscle bands of the rabbit right ventricle during glucose oxidation were investigated. The kinetics of fluorescent responses consists of two phases: the primary one--the fall, and secondary one--the rise of NADN fluorescence up to the initial level and higher (overshoot). The fluorescence change in the first phase and overshoot value increase in response to an increased mechanical load, as well as to an increased concentration of extracellular Ca++ or adrenaline injection.