Begell House Inc.
International Journal of Physiology and Pathophysiology
IJPP
2155-014X
1
3
2010
Effects of RNA on Blood Circulation and Its Adrenergic and Cholinergic Regulation
201-210
10.1615/IntJPhysPathophys.v1.i3.10
Oleksander P.
Neshcheret
Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
Zenovii Yu.
Tkachuk
Institute of Molecular Biology and Genetics of the National Academy of Sciences of Ukraine, Kyiv
Oleksiy O.
Moibenko
International Center for Astronomical and Medico-Biological Research, National academy of Sciences of Ukraine, Department of Experimental Cardiology, Department of General and Molecular Pathophysiology, Bogomoletz institute of Physiology, Kyiv, Ukraine
circulation
heart
coronary vessels
adrenergic regulation
cholinergic regulation
microRNA agent Nucleks
Experimental investigations of the impacts of small RNA agent Nucleks on heart function, coronary and systemic circulation as well as on adrenergic and cholinergic mechanisms of cardiohaemodynamics regulation were performed on anaesthetized dogs. Bolus injection (0.1 − 100.0 mg) or prolonged infusion (2.5 mg/min) of Nucleks into perfusion coronary artery blood stream induced coronary dilatation. Under the intracoronary infusion of Nucleks we observed more pronounced coronary vasodilatation and left ventricle pressure elevation in response to adrenergic heart receptors stimulation by norepinephrine (0.05 − 5.0 mkg, intracoronary). Besides that the drug infusion into coronary blood stream promoted the acceleration of recovery processes of the studied cardiohaemodynamics parameters after norepinephrine injection. After intracoronary infusion of Nucleks the sensitivity of cholinergic receptors to the stimulation by acetylcholine (0.001 − 1.0 mkg, intracoronary) increased significantly. After NO-synthase blockade (L-NAME, infusion 2.0 mg/min, intracoronary) Nucleks did not cause any effect on coronary vessels tone and heart activity both it did not change their adrenergic and cholinergic reactivity.
Cardioprotective Effects of Flocalin in In Vivo Experiments: Influence of the Hemodynamic and on the Damage of Myocardium under Ischemia-Reperfusion
211-218
10.1615/IntJPhysPathophys.v1.i3.20
Ruslan B.
Strutynskyi
Bogomoletz Institute of Physiology of the National Academy of Sciences of Ukraine, Kyiv
Oleksander P.
Neshcheret
Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
Lesya V.
Tumanovska
Department of General and Molecular Pathophysiology, Bogomoletz institute of Physiology, Kyiv, Ukraine
Roman A.
Rovenets
Bogomoletz Institute of Physiology of the National Academy of Sciences of Ukraine, Kyiv
Oleksiy O.
Moibenko
International Center for Astronomical and Medico-Biological Research, National academy of Sciences of Ukraine, Department of Experimental Cardiology, Department of General and Molecular Pathophysiology, Bogomoletz institute of Physiology, Kyiv, Ukraine
KATP channels
flocalin
ischemia-reperfusion
hemodynamic
infarct
In experiments on anesthetized dogs with experimental ischemia (90 min) and reperfusion (180 min) we show the cardioprotective effect of preischemic activation of ATP- sensitive potassium channels (KATP) using intravenous injection of fluorine-containing opener of these channels − flocain in concentration of 0.1 mg/kg, which practically did not change hemodynamic measures under normoxia. Thus, our investigations of flocalin impact on changes in hemodynamic during myocardium ischemia-reperfusion syndrome have shown some peculiarities of ischemia-reperfusion syndrome development under KATP-channels stimulation. From our point of view the positive impacts of flocalin which can support its cardioprotective effects can be arterial pressure lowering, which eases tension on the injured heart and promotes cardiac output retention during the first hours of ischemia. Flocalin-mediated prevention of increase of coronal vascular resistance and retention of myocardial contractility measurements during reperfusion period are of a great importance. All above mentioned flocalin properties promote the reduction of the myocardial infarction area after ischemia-reperfusion by 37% as compared to control.
An Increased Ca2+ Sensitivity of Mitochondrial Permeability Transition Pore in Rat Hearts with Nigrostriatal Dopamine Chronic Deficiency
219-226
10.1615/IntJPhysPathophys.v1.i3.30
Sergiy O.
Talanov
Bogomoletz Institute of Physiology of the National Academy of Sciences of Ukraine, Kyiv, Ukraine
Snezhana V.
Timoshchuk
Bogomoletz Institute of Physiology, National Academy of Science of Ukraine, Kyiv
Olena V.
Rudyk
Bogomoletz Institute of Physiology of the National Academy of Sciences of Ukraine, Kyiv
Vadim F.
Sagach
Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
dopamine deficiency
myocardium
mitochondria permeability transition pore
melatonin
We studied the sensitivity of mitochondrial permeability transition pore (MPTP) opening in response to natural inductor − Ca2+ ions in the rat heart mitochondria which chronic deficiency of nigostriatal dopamine caused by an injection of selective neurotoxin 6-xydroxidofamine in an ascending lateral bundle of the forebrain. MPTP-opening was determined spectrophotometrically (λ = 520 nm) by a decrease in an optical density resulting from mitochondria swelling. It has been shown that the rat heart mitochondria with chronic deficiency of nigrostriatal dopamine are more sensitive to Ca2+ in its physiological concentrations (10−7 M) and overload (10−6 − 10−4 M) in comparison to control animals. Thus, obtained results lead to a conclusion that an increased sensitivity of the mitochondrial permeability transition pore to calcium and mitochondrial membrane permeability may be one of the causes previously reported of disturbance in contractile function of the rat heart with chronic deficiency in nigrostriatal dopamine.
Production of Immunoregulatory Cytokines at Autoimmune Damage of Mammalian Ovaries
227-234
10.1615/IntJPhysPathophys.v1.i3.40
Roman I.
Yanchii
Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
Tetyana Yu.
Voznesenska
Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
Olena A.
Shepel
Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
Tetyana M.
Bryzgina
Bogomoletz Institute of Physiology of the National Academy of Sciences of Ukraine, Kyiv
Vera S.
Sukhina
Bogomoletz Institute of Physiology of the National Academy of Sciences of Ukraine, Kyiv
L. M.
Lazarenko
Kyiv Taras Shevchenko National University, Kyiv, Ukraine
Z. M.
Olenivska
Zabolotny Institute of Microbiology and Virology of the National Academy of Sciences of Ukraine, Kyiv
Mykola Ya.
Spivak
Zabolotny Institute of Microbiology and Virology of the National Academy of Sciences of Ukraine, Kyiv
R. M.
Serbenjuk
Zabolotny Institute of Microbiology and Virology of the National Academy of Sciences of Ukraine, Kyiv
O. M.
Serdyuk
Zabolotny Institute of Microbiology and Virology of the National Academy of Sciences of Ukraine, Kyiv
interferon
tumor necrosis factor-alpha
immune damage of ovaries
Several ovarian disorders in women are associated with autoimmune factors. In this study it was investigated a level of cytokines − TNF-α and IFNs in ovarian homogenate and blood serum at ovarian autoimmune damage of mammals. Experimental immune ovarian failure was induced in CBA mice by either immunization with allogenic ovarian extracts or administration of xenogenic anti-ovarian antibodies. Both models were accompanied with abnormalities in production immunoregulatory cytokines. These data confirm importance of definition of proinflammatory cytokine level for disclosing immune mechanisms which lay in a pathogenesis autoimmune ovarian diseases of female reproductive organs.
Histological and Hormonal Characteristic of Microencapsulated Human Parathyroid Tissue in Long-Term Culture
235-243
10.1615/IntJPhysPathophys.v1.i3.50
Ihor P.
Pasteur
State Institution V.P. Komisarenko Institute of Endocrinology and Metabolism of the AMS of Ukraine, Kyiv
Iryna A.
Balla
State Institution V.P. Komisarenko Institute of Endocrinology and Metabolism of the AMS of Ukraine, Kyiv
Andriy Ye.
Kovalenko
State Institution V.P. Komisarenko Institute of Endocrinology and Metabolism of the AMS of Ukraine, Kyiv
Mykola D.
Tronko
Komisarenko Institute of Endocrinology and Metabolism, National Academy
of Medical Sciences of Ukraine, Kyiv, Ukraine
parathyroid
microencapsulation
cultivation
histology
parathormone
Microencapsulated human parathyroid tissue preserves the viability and high ability to secrete parathormone in long-term culture, which testifies to perspective of further study of efficiency of using this tissue in the presence of compensated hypofunctional state of parathyroid system experimentally on animals.
Changes in UCP2 and UCP3 Genes Expression, in Heart Function and Oxygen Cost of Myocardial Work under Aging and Ischemia-Reperfusion
245-258
10.1615/IntJPhysPathophys.v1.i3.60
Yulia V.
Goshovska
Bogomoletz Institute of Physiology of the National Academy of Sciences of Ukraine, Kyiv
Olexandr O.
Lisovyi
Bogomoletz Institute of Physiology of the National Academy of Sciences of Ukraine, Kyiv
Tetyana V
Shimanskaya
Bogomoletz Institute of Physiology of the National Academy of Sciences of Ukraine, Kyiv
Vadim F.
Sagach
Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
uncoupling proteins UCP2 and UCP3
isolated heart
aging
ischemia- reperfusion
mitochondrial permeability transition pore
mitochondrial membrane potential
To examine effects of ischemia-reperfusion on UCP's genes expression, heart function and oxygen cost of myocardial work hearts of adult (6 mo) and old (24 mo) rats were perfused by Langendorf preparation and subjected to 20 min ischemia and 40 min of reperfusion. Mitochondrial permeability transition due to ischemic stimuli was evaluated by release of mitochondrial factor (λ = 250 nm) which was previously shown as a marker of MPTP opening. Expression of UCPs was detected by reverse transcriptional polymerase chain reaction. Mitochondrial membrane potential (Δψm) and oxygen consumption in isolated heart mitochondria of adult and old rats were measured. It was shown that impaired function of aging rat hearts was accompanied with increased oxygen cost of myocardial work and lower mitochondrial membrane potential comparing with adult rats. At the same time no mitochondrial factor was detected in initial state. Reperfusional disturbances of cardiodynamic, contractile activity of myocardium and noneffective oxygen utilization in early period of reperfusion were less intensive in aged hearts than in adult ones. However, it was detected greater amount of mitochondrial factor in outflow solution in reperfused aged heart indicating excessive MPTP opening. Levels of mRNA of UCP2 in aging hearts were higher and mRNA levels of UCP3 were tended to increase. Expression of UCP2 and UCP3 in adult myocardium was stimulated by ischemia- reperfusion, whereas there was no such effect in aging hearts. It is concluded that MPTP and uncoupling proteins are implicated in age-depended heart dysfunction and pathological mechanisms developed during ischemia-reperfusion.
siRNA-Mediated Silencing of 5-Lipoxygenase Gene (ALOX5) Reduces Necrosis of Cardiomyocytes at Anoxia- Reoxygenation
259-266
10.1615/IntJPhysPathophys.v1.i3.70
Olexandr O.
Lisovyi
Bogomoletz Institute of Physiology of the National Academy of Sciences of Ukraine, Kyiv
Vasyl S.
Nagibin
Bogomoletz Institute of Physiology of the National Academy of Sciences of Ukraine, Kyiv
Olga V.
Surova
Bogomoletz Institute of Physiology of the National Academy of Sciences of Ukraine, Kyiv
Lesya V.
Tumanovska
Department of General and Molecular Pathophysiology, Bogomoletz institute of Physiology, Kyiv, Ukraine
Viktor E.
Dosenko
Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
Oleksiy O.
Moibenko
International Center for Astronomical and Medico-Biological Research, National academy of Sciences of Ukraine, Department of Experimental Cardiology, Department of General and Molecular Pathophysiology, Bogomoletz institute of Physiology, Kyiv, Ukraine
ALOX5
RNA interference
cardiomyocytes
anoxia-reoxigenation
In experiments on the primary culture of isolated neonatal rat cardiomyocytes it was determined that cardiomyocytes express ALOX5 gene encoding enzyme 5-lipoxygenase. Anoxia-reoxygenation does not affect significantly expression of 5-lipoxygenase mRNA in cardiomyocytes. Transfection into cardiomyocytes 5-lipoxygenase-specific small interfering RNA's (siRNA) lead to significant reducing of 5-lipoxygenase mRNA expression in cardiomyocytes after 24 hours of cultivation. ALOX5 gene silencing resulted in improved cell survival during anoxia-reoxygenation. Obtained results indicate that siRNA against ALOX5 effectively protects cardiomyocytes against A/R injury.
The Effect of Lomg-Term Exercise Training on the Changes in the Functional State of Heart duringIschemia-Reperfusion, the Sensitivity of Calcium- Induced Mitochondrial Permeability Transition Pore and the Uncoupling Protein 3 Expression
267-276
10.1615/IntJPhysPathophys.v1.i3.80
Nataliya A.
Strutynska
Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
Snizhana V.
Chorna
Bogomoletz Institute of Physiology, National Academy of Science of Ukraine, Kyiv
Sergiy O.
Talanov
Bogomoletz Institute of Physiology of the National Academy of Sciences of Ukraine, Kyiv, Ukraine
Galyna L.
Vavilova
Bogomoletz Institute of Physiology, National Academy of Science of Ukraine, Kyiv
N. M.
Gaidai
Bogomoletz Institute of Physiology, National Academy of Science of Ukraine, Kyiv
Vadim F.
Sagach
Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
ischemia-reperfusion
MPTP
UCP3
The effect of long exercise training on the indexes of the functional state isolated by Lanhendorf rat hearts during ischemia-reperfusion, the sensitivity of calcium-induced NO-dependent mitochondrial permeability transition pore (MPTP) opening as well as the mitochondrial uncoupling protein 3 (UCP3) expression were investigated. The obtained results indicate the positive effect of long exercise training on the heart functional state. Reperfusion injurings of the heart contractile function and its myocardial oxygen metabolism were less pronounced in adapted to exercise loading rats (trained rats). It was shown that the sensitivity of mitochondrial permeability transition pore opening to its inductor Ca2+ in the trained rats heart decreased compared with control animals. Thus, in the trained rat heart mitochondria had a significant increase in cNOS activity (almost twice), slight increase in the iNOS activity compared with control, and a slight increase in the hydrogen peroxide level. Under adaptation to the long exercise training, the expression level of UCP3 in rat heart mitochondria was reduced by 65 % compared with the control. These results suggest that the decrease in the expression level of UCP3 in the adaptation of animals to exercise training may play the certain role in the complex mechanism of adaptive response of the heart, that may be aimed mainly on the efficiency of oxidative phosphorylation in mitochondria and, consequently, to increase in the ATP synthesis. Thus, long exercise training contributes to the improvement of the heart functional state, namely, its contractile function, and also increases the resistance to reperfusion injury, reducing the sensitivity of the MPTP opening to the action of calcium ions by increasing the activity of mitochondrial constitutive NOS and synthesis of nitric oxide, an endogenous inhibitor of MPTP opening.
Influence of Endothelial Nitric Oxide Synthase T−786→C Promoter Polymorphism on Integral Parameters of Functional Condition of Arterial Vessels
277-286
10.1615/IntJPhysPathophys.v1.i3.90
Alexandr N.
Parkhomenko
National Scientific Center M.D. Strazhesko Institute of Cardiology, Medical Academy of Sciences of Ukraine, Kiev
Yaroslav M.
Lutay
National Scientific Center M.D. Strazhesko Institute of Cardiology, Medical Academy of Sciences of Ukraine, Kiev
Viktor E.
Dosenko
Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
Veronika L.
Gurianova
Bogomoletz Institute of Physiology, NAS of Ukraine, Kyiv, Ukraine
Oleksiy O.
Moibenko
International Center for Astronomical and Medico-Biological Research, National academy of Sciences of Ukraine, Department of Experimental Cardiology, Department of General and Molecular Pathophysiology, Bogomoletz institute of Physiology, Kyiv, Ukraine
Alexandr A.
Skarzevskiy
National Scientific Center M.D. Strazhesko Institute of Cardiology, Medical Academy of Sciences of Ukraine, Kiev
allelic polymorphism
endothelial NO-synthase
endothelial dysfunction
speed of pulse wave spreading
acute coronary syndrome
Frequency of eNOS Т−786→С promoter polymorphism in 325 patients with acute coronary syndrome and 104 control persons and influence of this polymorphism on reactive hyperemia and arterial stiffness were determined. Interrelation between T/T homozygous, T/С heterozygous and С/С homozygous was 42.5 %, 41.2 % and 16.3 % correspondingly (in control − 40.4 %, 53.8 % and 5.8 %; Р < 0.01 by χ2-test). Higher degree of brachial arteries diameter increase in response to ischemia was estimated in patients with Т/Т genotype: 8.03 ± 0.71 % compared to 5.55 ± 0.92 % in Т/С (Р < 0.05) and 5.30 ± 1.21 % in С/С genotypes (P < 0.05). Speed of pulse wave spreading on carotid-radial and carotid-femoral arteries segments was also depended on patients genotype: in Т/Т genotype was 9.10 ± 0.15 and 8.68 ± 0.26 correspondingly, in Т/С - 9.38 ± 0.18 and 8.74 ± 0.21, and in С/С carriers - 9.71 ± 0.22 and 10.02 ± 0.71 (P < 0.05). Thus, obtained data indicate on significantly influencing of Т−786→С promoter polymorphism on integral parameters of functional condition of arterial vessels.
Molecular and Cellular Mechanisms of Alzheimer's Disease Development
287-304
10.1615/IntJPhysPathophys.v1.i3.100
Elena P.
Kostyuk
Bogomoletz Institute of Physiology of the National Academy of Sciences of Ukraine, Kyiv
Tatyana Yu.
Korol
Bogomoletz Institute of Physiology of the National Academy of Sciences of Ukraine, Kyiv
Platon G.
Kostyuk
Bogomoletz Institute of Physiology of the National Academy of Sciences of Ukraine, Kyiv
Alzheimer's disease
amyloid
calcium homeostasis
synaptic plasticity
mitochondria
endoplasmic reticulum
calcium channels
Neuropathological studies classified several neurodegenerative illnesses among which Alzheimer's and Parkinson diseases are the most frequent. Alzheimer's disease is characterized by the presence of cognitive syndromes and almost completes destruction of memory. It is suggested that the basis of these syndromes is an elevation of the amount of β-amyloid-42 protein (mainly in hippocampal neurons), changes in calcium homeostasis and synaptic plasticity. Recent data indicate that alterations of calcium homeostasis connected with changes in neuronal membrane and functioning of the endoplasmic reticulum, leading to long − lasting alterations synaptic potenthiation and depression. Therefore the task of this review was the analysis of alterations in the functioning of structures involved in calcium homeostasis, including mitochondria, calcium channels, processes leading to changes in synaptic plasticity. Beside this we wanted to decide which process are the leading ones in the development of Alzheimer's disease − accumulation in hippocampal neurons and dendrites of β-amyloid or alteration in calcium homeostasis (mainly from the data of literature).