Begell House Inc.
International Journal of Physiology and Pathophysiology
IJPP
2155-014X
6
3
2015
Effects of Deltaran and Melatonin on Immune System in Rats in Experimental Contact Dermatitis
177-183
10.1615/IntJPhysPathophys.v6.i3.10
Oleksii O.
Shandra
"Odessa National Medical University"
experimental contact dermatitis
immune reactivity
neutrophil alteration index
lymphocyte alteration index
deltaran
melatonin
pharmacological correction
We investigated the activity of humoral and cellular links of immunity and leukocyte functional stability indicators in rats with experimental contact dermatitis (ECD) under pharmacological correction by application of deltaran and melatonin. Chronic experiments were performed on the model of chrome-induced ECD. Complex pharmacological correction of humoral and cellular links of immunity and leukocyte stability was assessed using separate and combined administrations of deltaran and melatonin. The results have shown the pronounced disturbances in humoral and cellular links of immunity, as well as neutrophil and lymphocyte functional stability under chrome-induced ECD in rats. Violations of the functional activity of the immune system were corrected by applications of deltaran and melatonin. The activity of the therapeutic complex had exponential character.
Effect of Enzymatic Treatment Using Proteases on Properties of Persistent Sodium Current in CA1 Pyramidal Neurons of Rat Hippocampus
185-189
10.1615/IntJPhysPathophys.v6.i3.20
Oleksiy O.
Lunko
Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
Dmytro S.
Isaev
Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
Oleksandr P.
Maximyuk
Bogomolets Institute of Physiology, National Academy of Sciences of
Ukraine, Kyiv, Ukraine
Oleg O.
Krishtal
Bogomolets Institute of Physiology, National Academy of Sciences of
Ukraine, Kyiv, Ukraine
Olena V.
Isaeva
Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
persistent sodium current
enzymatic treatment
protease
We investigated the effect of proteases, widely used for neuron isolation in electrophysiological studies, on the amplitude and kinetic characteristics of persistent sodium current (INaP) in hippocampal CA1 pyramidal neurons. Properties of INaP were studied on neurons isolated by mechanical treatment (control group) and by mechanical and enzymatic treatment using pronase E (from Streptomyces griseus) or protease type XXIII (from Aspergillus oryzae). We have shown that kinetics of activation and density of INaP in neurons isolated with pronase E was unchanged. Enzymatic treatment with protease type XXIII did not alter INaP activation but resulted in a significant decrease in INaP density. Our data indicate that enzymatic treatment with pronase E for neuron isolation is preferable to investigate INaP.
Hematological Effects of Protein Kinases Inhibitor Maleimide Derivative in Dimethylhydrazine-Induced Colorectal Carcinogenesis in Rats
191-201
10.1615/IntJPhysPathophys.v6.i3.30
Iryna V.
Byelinska
Taras Shevchenko National University of Kyiv, Kyiv, Ukraine
Oksana V.
Lynchak
Kyiv Taras Shevchenko National University, Kyiv, Ukraine
Taras V.
Rybalchenko
Taras Shevchenko National University of Kyiv, Kyiv, Ukraine
Oksana M.
Gurnyak
Taras Shevchenko National University of Kyiv, Kyiv, Ukraine
maleimide derivative
protein kinase inhibitor
1
2-dimethylhydrazine-induced colon carcinogenesis
erythrocytes
leukocytes
platelets
The effect of the protein kinases inhibitor maleimide derivative (MI-1, 1-(4-Cl-benzyl)-3-Cl-4-(CF3-phenylamino)-1H-pyrrole-2, 5-dione) on the blood cells of rats with 1, 2-dimethylhydrazine (DMH)-induced colon carcinogenesis was studied. It has been revealed that the introduction of MI-1 in a dose of 2.7 mg / kg for 20 weeks prevents anemia which accompanies cancer and complicates the course of the latter. This is evidenced by the reduction in the number of reticulocytes (0.19[0.15; 0.21]·1012/l) and restitution of the content (18.02 [17.44;19.03] pg) and concentration (309.42 [292.38;318.27] g/l) of hemoglobin in the erythrocytes to the control values (0.17 [0.15;0.19], 18.31 [17.95;18.45]), 310.78 [306.25;316.18], respectively) in contrast to the group injected with DMH (0.28 [0.24;0.39]; 17.50 [17.00;17.96]; 288.10 [284.71;303.73], respectively). MI-1 normalizes the count of monocytes (1.40 [0.95; 2.50] ·109 /l) and platelets (646.32 [575.23; 700.50] ·109 /l) in the blood after 26 weeks of experiment. In subjected to DMH rats, these parameters are significantly higher (1.97 [1.52; 2.58], 783.90 [687.64; 922.27], respectively) compared to the control group (1.23 [0.94; 1.68], 629.34 [590.19; 711.48], respectively). MI-1 reduces the involvement of these cells in the tumor progression and metastasis. Reduced monocytosis and thrombocytosis may be mediated by: 1) a decrease in the number of tumors and the area of colon lesions and, consequently, the influence of their cytokines on hematopoietic tissue; 2) an inhibition of proliferation and differentiation of hematopoietic progenitor cells through inhibiting receptor protein kinases of vascular endothelial and epidermal growth factors and non-receptor PDK1-, Src- and Syk-protein kinases that are involved in hematopoiesis and carcinogenesis.
Propargylglycine Restores Endothelium-Dependent Relaxation of Aortic Smooth Muscle in Old Rats
203-212
10.1615/IntJPhysPathophys.v6.i3.40
Konstantin O.
Drachuk
Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
Anatoliy V.
Kotsuruba
Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
Olga V.
Bazilyuk
Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
Lyubov G.
Stepanenko
Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
Vadim F.
Sagach
Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
propargylglycine
hydrogen sulfide
cystathionine-γ-lyase
acetylcholine
nitrogen oxide
endothelium
smooth muscle
aorta
aging
oxidative stress
Endothelium-dependent relaxation of the vascular smooth muscles (SM) is responsible for the development of basic cardiovascular reactions, and its violation is the basis of aging-associated cardiovascular diseases. We studied effects of inhibiting cystathionine-γ-lyase (CSE), the enzyme for de novo synthesis of hydrogen sulfide, on the endothelium-dependent relaxation of thoracic aorta SM from old rats. It has been shown that an inhibition of CSE by propargylglycine (PAG) results in restoration of decreased ACh-induced relaxation of aortic SM in old rats. That effect of PAG was removed by blocking nitric oxide (NO) synthesis in the endothelial cells. Age-related changes in the levels of H2S2 NO2−and enzyme activity of the constitutive synthesis of NO (cNOS) in the heart were determined. It has been demonstrated that introduced PAG elevates decreased levels of H2S2 NO2−and stimulates suppressed activity of cNOS in old rats. These results suggest that PAG activates alternative ways of H2S synthesis and stimulates the constitutive synthesis of NO to restore endothelial function in old rats.
The Content of Blood Leptin and Activity of Systemic Inflammatory Response in Patients with Type 2 Diabetes Mellitus depending on Weight and Length of the Process
213-219
10.1615/IntJPhysPathophys.v6.i3.50
Boris
Mankovsky
Lviv National Medical University, Lviv, Ukraine
Alina
Urbanovych
Lviv National Medical University, Lviv, Ukraine
type 2 diabetes mellitus
leptin
interleukin-2
interleukin-6
tumor necrosis factor α
The aim of the study was to establish the relationship between the blood leptin content and the markers of generalized non-specific inflammation in patients with type 2 diabetes mellitus (DM), depending on its duration, excess weight and obesity. We compared the contents of leptin, interleukins (IL) IL-2, IL-6, and tumor necrosis factor α (TNF-α) in groups with different duration of type 2 diabetes mellitus, in normal, overweight, and obese patients. In the patients with high leptin content, significantly lower levels of TNF-α (7.82 ± 0.34 ng / ml) have been found. The positive correlation of the latter with body mass index (r = 0.48, P < 0.0001) and IL-6 (r = 0.13, P = 0.019) was observed, resulting from the increased pool of visceral adipose tissue that produces leptin and 10 − 35% of IL-6. In patients with newly diagnosed type 2 diabetes mellitus, the levels of leptin (19.35 ± 1.39 ng / ml) and TNF-α (7.82 ± 0.94 ng / ml) were significantly lower compared to the control values. The highest contents of leptin and cytokines were observed in the patients with diabetes duration of 5 to 10 years. As a rule, cardiovascular complications are developed just in this period. In the group of patients with normal weight, the contents of leptin (6.39 ± 1.15 ng / ml) were the lowest, whereas the contents of TNF-α (11.37 ± 3.77 ng / ml) and IL-6 (10.12 ± 6.91 ng / ml) were the highest. Perhaps it is the high content of these cytokines that makes it possible to maintain a normal body weight in these patients. It is known that under prolonged glucose - and lipotoxicity metabolic immunosuppression emerges, defined by the changes in T-cell immunity, which also contributes to autoimmunity in type 2.diabetes mellitus.
The Role of Calcium Uniporter in Calcium Homeostasis of Extraorbital Lacrimal Gland Secretory Cells
221-230
10.1615/IntJPhysPathophys.v6.i3.60
Anna B.
Kotliarova
Bogomolets Institute of Physiology, NASU, Kyiv, Ukraine
Volodymyr M.
Merlavsky
Ivan Franko National University of L'viv, Ukraine
Olga M.
Dorosh
Ivan Franko National University of L'viv, Ukraine
Volodymyr V.
Manko
Ivan Franko National University, Lviv, Ukraine
Calcium-uniporter of mitochondria
ruthenium red
sarcoendoplasmic reticulum Ca2+ -ATPase (SERCA)
inositol-1
4
5-trisphosphate receptors (IP3Rs)
ryanodine receptors (RyRs)
lacrimal
The role of mitochondrial calcium-uniporter in the control of calcium homeostasis, and correlations of calcium-uniporter with other calcium-transport systems of the rat extraorbital lacrimal gland secretory cells were studied. The experiments were performed on intact and digitonin-permeabilized cells. The interdependence of calcium-uniporter and the operation of other calcium-transporting systems were assessed on the basis of the inhibitors/agonists effects additivity, the action of which was accompanied by a decrease in Ca2+ content in the gland cells. It has been revealed that simultaneous inhibition of the calcium pump in the sarco/endoplasmic reticulum (SERCA) and mitochondrial calcium-uniporter results in a passive release of Ca2+ from different calcium stores, since the effects of the inhibitors of calcium-transport systems (thapsigargin and ruthenium red, respectively) were additive. Similarly, the effects of activation of the inositol-1, 4, 5-trisphosphate receptors (IP3Rs) and inhibition of mitochondrial calcium-uniporter were additive. In contrast, the effects of ryanodine and ruthenium red on the Ca2+ content in cells were non-additive. In addition, ryanodine at concentrations 1 − 3 µM reduced respiration rate of studied cells in a dose-dependent manner, and the effect was persisted in cells pre-incubated with ruthenium red or thapsigargin. Thus, besides the activation of ryanodine receptors (RyRs) in the endoplasmic reticulum, ryanodine inhibits Ca2+ influx in the mitochondrial matrix that was insensitive to ruthenium red.
Alcohol-Associated Suppression of Strength Response by Musculus Gastrocnemius Caput Mediale in Rats with Critical Vascular Ischemia of Hind Limbs
231-248
10.1615/IntJPhysPathophys.v6.i3.70
Olexiy
Melnychuk
Lesia Ukrainka Eastern European National University, Lutsk, Ukraine
Olexander P.
Motuziuk
Lesia Ukrainka Eastern European National University, Lutsk, Ukraine
Svitlana Yu.
Zay
Lesia Ukrainka Eastern European National University, Lutsk, Ukraine
Dmytro N.
Nozdrenko
Taras Shevchenko National University of Kyiv, Kyiv, Ukraine
Kateryna I.
Bogutska
Taras Shevchenko National University of Kyiv, Kyiv, Ukraine
Yuriy P.
Sklyarov
Bogomolets National Medical University, Kyiv, Ukraine
Yuriy I.
Prylutskyy
Taras Shevchenko National University of Kyiv, Kyiv, Ukraine
alcoholic Wistar rats
musculus gastrocnemius caput mediale
critical vascular ischemia
The change in m. gastrocnemius caput mediale strength response in alcoholic rats was studied in conditions of experimentally induced critical vascular ischemia of hind limbs. The experiment was performed on 30 male 5 months old Wistar rats weighing 145 - 150 g. Chronic alcohol intoxication of the animals was induced by intragastric delivery of 40% ethyl alcohol for 30 days. Unilateral vascular ischemia was induced by ligating a. femoralis. The mechanical activity of the muscle was registered in isometric contraction under conditions of applied stimulation. To describe the change in muscle strength response to each tetanic contraction, we calculated tetanic force, time to tetanus peak, fusion and fatigue indices. Also, for the last muscle contraction in each tetanic contraction, we calculated the time of contraction, the time of half-relaxation and speed-force index. The alcohol-associated suppression of m. gastrocnemius strength response in alcoholic rats is proved by a low initial tetanus force, which is 50% of the muscle initial force in the controls and non-alcoholic rats. The rate of decrease in the muscle tetanic force during the experiment with alcoholic rats proved to be greater than that in non-alcoholic rats. This fact together with the low values of isometric force developed by the muscle evidences that muscle atrophy in the animals is caused by alcohol. However, no pronounced differences have been found for the time of attaining tetanic force peak and fusion index for alcoholic rats in comparison with non-alcoholic animals. The analysis of time course of the last muscular contraction in tetanus has not revealed any profound change in duration of intervals between contractility in the tetanus. However, we have found reliable changes in the direction of muscle force development: in alcoholic and non-alcoholic rats the muscle develops force at an acute angle in comparison with the controls, which indicates ischemia-associated destabilization of myofibrils. The obtained results show the gathering evidence of the synergy of ethyl alcohol myotoxic effects and destructive influence of vascular ischemia by reducing contractility of m. gastrocnemius in alcoholic rats, which results in intensified ischemia-associated motor dysfunction.
Changes in Processes of Free Radical Oxidation of Lipids and Proteins, Antioxidant Defense in Rats with Thyroid Hypofunction against Iodine and Copper Deficiency
249-259
10.1615/IntJPhysPathophys.v6.i3.80
Natalia M.
Voronych-Semchenko
Ivano-Frankivsk National Medical University, Ministry of Health of Ukraine, Ivano-Frankivsk, Ukraine
Tetyana V.
Guranych
Ivano-Frankivsk National Medical University, Ministry of Health of Ukraine, Ivano-Frankivsk, Ukraine
thyroidhypofunction
microelement imbalance
free radical oxidation of lipids
peroxidative oxidation of proteins
antioxidant system
Thyroid status, copper balance, correlation of processes of peroxide oxidation of lipids (POL), proteins (POP), antioxidant defense (AOD) were examined in experiments on rats with hypofunction of thyroid gland against iodine monodeficit (THI) and combined iodine and copper deficiency (THI+Cu). It has been found that combined deficiency of microelements is accompanied by copper redistribution between different tissues (an increase in the levels of the latter in the red blood cell mass and the brain, and a decrease in copper content in the myocardium), as well as essential changes in indexes of hypothalamic-pituitary-thyroid axis, oxygen-dependent metabolism, anti-radical protection, exacerbating negative effects of each of them on the body. It has been revealed that THI+Cu inhibits oxygen-dependent processes, as evidenced by a decrease in the content of dyenic conjugates (DC) by 69.70% in the thyroid gland, TBA-reacting products (TBA-RP) by 47.72% in the diencephalon, the products of oxidative modified proteins (OMP) by 37.10 − 98.98% in the tissues of the diencephalon, the thyroid gland and the liver against the background of selective activation of peroxidation in the blood serum (an increase in TBA-RP content 7.11 times), and in the myocardium (an increase in DC level 2.86 times, OMP − 2.64 times) in comparison with the same indexes in intact animals. The results obtained (manifestations of the POL and POP processes, a decrease in copper concentration in the myocardium of examined animals) let us suppose the key role of microelement disbalance and metabolic mechanisms in pathogenesis of cardiac pathology against the background of thyroid dysfunction. The development of HTGI+Cu exhausts the resources of AOD, as evidenced by a decrease in the activity of catalase (by 47.05%), superoxide dismutase (by 33.13%), and saturation of transferrin with iron (by 56.76%) in comparison with the control data. The long-term disturbances of AOD may be the reason for enhancing oxygen-dependent processes and the development of pathological changes in separate physiological systems of the body.
Pathophysiological Mechanisms of Intrahepatic Portal Hypertension Syndrome
261-267
10.1615/IntJPhysPathophys.v6.i3.90
Taras V.
Romaniuk
Ivan Horbachevsky Ternopil State Medical University, Ternopil, Ukraine
Ihor Ya.
Dziubanovskyi
Ivan Horbachevsky Ternopil State Medical University, Ternopil, Ukraine
Oleh V.
Kuziv
Ivan Horbachevsky Ternopil State Medical University, Ternopil, Ukraine
pathogenesis
portal hypertension syndrome
complications of portal hypertension
The review presents current understanding of pathophysiological mechanisms leading to intrahepatic portal hypertension syndrome, as well as the development of major complications, such as esophageal varices, cardial bleeding, ascites, hypersplenism.