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GENETIC ASPECTS OF BETA1-BLOCKERS TREATMENT FOR PATIENTS WITH HYPERTENSION

Authors: Dudchenko I.O., Prystupa L.N.

Pages: 246-255

Abstract

Introduction. Analysis of scientific studies has revealed the relationship between the T393C polymorphism of GNAS1 gene and Arg389Gly of ADRβ1 gene, and effectiveness of treatment using β1-blockers. However, these results are controversial, which may be due to ethnicity of the studied groups. In Ukraine, the study of T393C polymorphism of GNAS1 gene and its impact on the effectiveness of antihypertensive therapy using β1-blockers were not carried out.

Our aim was to determine the impact T393C polymorphisms of gene GNAS1 and Arg389Gly of ADRβ1 gene on efficiency of treatment using β1-blockers for patients with hypertension.

Materials and methods. The study involved 70 patients with verified diagnosis of hypertension. At baseline, β1‑blockers were appointed for patients at doses: metoprolol – 12.5 mg/kg per day, carvedilol – 25 mg/kg per day, and bisoprolol – 5 mg/kg per day. Efficacy of treatment was determined after 2 weeks by measuring heart rate and blood pressure. Polymorphism of gene was determined by polymerase chain reaction followed by restriction fragment analysis. Statistical analysis of the data was performed using the SPSS Statistics 21.0 program.

Discussion. It is proved that determining of T393C polymorphisms of GNAS1 gene and Arg389Gly of ADRβ1 gene plays an important role for the treatment with β1-blockers, because:

    • in patients with T393T genotype of GNAS1 gene observed higher level of reduction of systolic blood pressure and heart rate, when the treatment by β1-blocker was used, than in patients with C393C genotype;
    • in patients with Arg389Arg and Arg389Gly genotypes of ADRβ1 gene the level of reduction of heart rate and systolic blood pressure, when the treatment by β1‑blocker was used, was higher than in patients with Gly389Gly genotype.
    • in case when T393C or C393C genotypes of GNAS1 gene and Gly389Gly of ADRβ1 gene are combined, application of β1-adrenergic blockers is ineffective, even with its dose adjustment.

Key words: β1-blockers, gene polymorphism, heart rate, blood pressure.

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INTESTINAL HOMEOSTASIS AND HIV-INFECTION (REVIEW)

Authors: Dyachenko A.G., Gorobchenko K.M., Savinova E.V., Miroshnechenko E.A.,Shkrioba O.A.

Pages: 259-272

Abstract

  

Permanent balance between microbiota, intestinal barrier and mucosal immune system is the basis of the normal intestinal homeostasis. HIV infection leads to significant violations of the immune status and structural damage of the intestinal mucosa that is a threat barrier function. The weakening of the immune pressure leads to disbiotic processes and microbial translocation that causes chronic activation of the immune system and the progression of HIV infection. Although the introduction of combined antiretroviral therapy is a great achievement in the treatment of HIV infection remains a need for some additional measures aimed to restorethe structure and functional integrity of the intestinal epithelium.

The hypothesis that probiotic administration protects the gut surface and can delay progression of HIV infection to the AIDS was proposed in 1995. Over the last five years, new studies have clarified the significance of HIV-1 infection of the gut associated lymphoid tissue (GALT) for subsequent alterations in the microflora and breakdown of the gut mucosal barrier leading to pathogenesis and development of AIDS. Current studies show that loss of gut CD4+ Th17 cells, which differentiate in response to normal microflora, occurs early in HIV-1 disease. Microbial translocation and suppression of the T regulatory (Treg) cell response is associated with chronic immune activation and inflammation. Combinations of probiotic bacteria, which upregulate Treg activation, have a promising effect in suppressing pro inflammatory immune response in models of autoimmunity including inflammatory bowel disease and provide a rationale for use of probiotics in HIV-1/AIDS. Disturbance of the microbiota early in HIV-1 infection leads to greater dominance of potential pathogens, reducing levels of bifidobacteria and lactobacillus species and increasing mucosal inflammation. The interaction of chronic or recurrent infections and immune activation contributes to nutritional deficiencies that have lasting consequences. As discussed here, current and emerging studies support the concept that probiotic bacteria can provide specific benefit in HIV-1 infection.

Key words: intestinal microbiota, intestinal barrier, dysbacteriosis, HIV infection.

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Yin L, Rodriguez CA, Hou W, Potter O, Caplan MJ, Goodenow MM, Sleasman JW. Antiretroviral therapy corrects HIV-1-induced expansion of CD8+ CD45RA+ CD27− CD11a(bright) activated T cells. J Allergy Clin Immunol. 2008;122(1):166–172.

 

CEREBROPROTECTIVE ACTIVITY OF PIRACETAM UNDER COADMINISTRATION WITH HYPOGLYCEMIC, ANTIOXIDANT OR ANTIPLATELET DRUGS IN EXPERIMENTAL DIABETES

Authors: ZhyliukV.I., MamchurV.I., LievykhA.E., Petruk N.S.

Pages: 273-282

Abstract

  

The paper presents the results of research of piracetam cerebroprotective activity under coadministration with hypoglycemic, antioxidant or antiplatelet drugs in rats with hyperglycemia.

Research was carried out on 70 white rats weighing 250–300 g. Experimental diabetes was initiated by subcutaneous injection of alloxan monohydrate. On the 11th day after administration of alloxan the animals were randomized in 7 groups : I – intact (distilled water); II – diabetes (distilled water); III – diabetes + piracetam (500 mg/kg); IV – diabetes + piracetam (400 mg/kg) + metformin (500 mg/kg); V – diabetes + piracetam (400 mg/kg) + pioglitazone (10 mg/kg); VI – diabetes + piracetam (400 mg/kg) + thiotriazoline (100 mg/kg); VII – diabetes + piracetam (400 mg/kg) + acetylsalicylic acid (50 mg/kg). Experimental combinations and distilled water were administered intragastrically for 20 days.

We assessed content of protein oxidative modification markers and total level of nitrates/nitrites in homogenates of neocortex using spectrophotometric analysis. Ultrastructural studies of neocortical tissue were performed using a transmission electron microscope TEM-100-01 according to the standard plan.

We found that experimental model of diabetes was accompanied by the development of carbonyl stress and led to overproduction of nitric oxide in neocortex. Piracetam, when used with metformin, thiotriazoline or acetylsalicylic acid, significantly reduced content of early and late markers of protein molecules degradation (aldehydephenylhydrazones and ketonephenylhydrazones) and decreased level of nitric oxide stable metabolites. Coadministration of piracetam with pioglitazone did not result in considerable effect on content of these substances. We established that the use of all experimental drug combinations did not provide full recovery of ultrastructural changes in the neocortex; however, coadministration of piracetam with thiotriazolin, acetylsalicylic acid and metformin, but not with pioglitazone, led to a significant limitation of destructive changes in neurons and synaptic mechanism. Cerebroprotective activity of the combinations did not depend on the presence of hypoglycemic properties.

Key words: piracetam, metformin, pioglitazone, thiotriazoline, acetylsalicylic acid, protein oxidative modification, nitric oxide, diabetes, neocortex.

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THE EFFECT OF LAPROXIDES ON BLOOD SERUM PHOSPHORESCENCE INTENSITY IN SUBACUTE TRIAL AND ITS PROGNOSTIC VALUE

Authors: Kucheriavchenko M.A.

Pages: 283-291

Abstract

  

Introduction. The investigatedxenobiotics are employed to produce plastic, epoxide resins, varnishes, enamels, paints, foam plastic and et cetera. The study of pathophysiological mechanisms triggering structural and metabolic disorders in response to prolonged subtoxic exposure on the body was commissioned by the absence of prognostic characteristics of potential danger, which laproxides can constitute for hematothermal animals and humans. The study showed that determination of integral intensity of blood serum phosphorescence would become a promising methodological approach in early diagnosis of blood serum protein capacity. Considering its high sensitivity and informative value, phosphorescence enables to detect abnormalities when studying electron excitation states of molecules, photochemical reactions, fast molecular transition dynamics, structures and properties of chemical and biological systems. Properties and differences of protein exchange and their conformational compact structure tend to develop with the progression of the impairment. Previous studies have confirmed that alteration of qualitative properties of proteins is always associated with the impairment of their main functions, such as enzyme, hormone, receptor, transport, structural, mechanical, supporting, reserve, substrate-energetic, contractile, electro-osmotic, energy transforming, cogenic, gene regulating, immunologic, anti-toxic, neutralizing and hemostatic functions.

The aim was to determine the effect of laproxides in response to prolonged subtoxic exposure on the indices of blood serum phosphorescence in white rats and assess its prognostic value.

Material and Methods. The study implied determination of blood serum phosphorescence intensity in animals exposed to peroral exposure to epoxide-containing oligo-ethers in dosages of 1/10; 1/100 and 1/1000 DL50 during 45 days. New substances (the trade name “Laproxides”) were employed, namely triglycidyl ether of polyoxypropylene triol with molecular mass 303 (L-303) and ethylene glycol propylene epoxide with molecular mass 500 (L-500). Aqueous solutions of the substances at the above mentioned doses were administered endogastrically with a metal feeding tube on an empty stomach in the morning. The control group received corresponding doses of drinking water.

Discussion. The study of laproxides L-303 and L-500 effect showed a significant increase in blood serum phosphorescence intensity in the group of animals in response to peroral exposure to xenobiotics in 1/10 and 1/100 DL50 dosages in spectral lines of excitation light 297; 313; 334; 365; 404 and 434 nm. In 1/1000 DL50 the substances did not exert any effect on blood serum phosphorescence intensity rate. Thus, high levels of phosphorescence intensity indicate that laproxides at subtoxic doses of 1/10 and 1/100 DL50 induce the development of significant amount of reactive molecules, capable to condition chain reactions of lipids, proteins, nucleic acids and other biological substrates oxidation. The results show that these compounds are capable of changing conformational properties of proteins, nucleic acids and nucleotides, as well as their functional activity, resulted from the formation of free radical membrane pathology.

Key words: xenobiotics, laproxides, blood serum phosphorescence.

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INFLUENCE OF IRON NANOPARTICLES ON INTESTINAL MICROFLORA OF RATS WITH IRON DEFICIENCY ANEMIA

Authors: Doroshenko A.M., Dybkova S.M., Rieznichenko L.S., Gruzina T.G., UlbergZ.R., Chekman I.S.

Pages: 292-299

Abstract

  

According to the WHO data, iron deficiency anemia (IDA) is one of the most widespread pathological states as well as social problem. IDA is also one of the most important causes of intestinal dysbacteriosis. Varieties of oral iron preparations are widely prescribed as a part of medical care for patients with IDA. However, iron of existing oral antianemic drugs is not usually effectively absorbed. It may lead to elevation of intestinal iron content. The excess of iron in intestine can also result in dysbacteriosis. Moreover, existing antianemic drugs are not usually effective and safe. Thus, either IDA or oral iron supplementation may cause intestinal dysbacteriosis. Therefore, synthesis and development of new classes of biosafe and biocompatible antianemic drugs is an urgent task. Iron nanoparticles are promising in this direction. Due to high biological activity of iron nanoparticles, preclinical study of their effectiveness and safety for IDA treatment should include determining of their impact on intestinal microflora. The aim of this work was to study the influence of iron nanoparticles on intestinal microflora under conditions of oral administration to rats with IDA.

Substance of 40 nm sized spherical zero-valent iron nanoparticles (FeNPs) used in this study have been synthesized according to the original protocol of chemical condensation in water medium by iron (III) chloride reduction. We studied biological activity of FeNPs, as potential pharmacological substance with antianemic properties, on the model of IDA using Wistar female rats. IDA in experimental animals was modelled using iron deficiency diet. The experimental treatment course of rats with IDA included 10 days oral administration of FeNPs at/in therapeutic (12 mg/kg) dose. Commercial preparation based on pharmacological substance ferri (III) hydroxydi polymaltosum complexus was used as comparison drug in therapeutic dose. The status of microflora in lower part of rats’ gastrointestinal tract after experimental treatment course has been determined using standard microbiological protocols.

According to microbiological tests, rats fed with iron deficient diet demonstrated intestinal dysbiosis. In this case, there was a significant reduction of the protective microflora (bifidobacteria and lactobacilli). After 10 days of experimental treatment course (either with FeNPs or comparison drug), we observed normalization of quantitative parameters of protective and transient intestinal microorganisms in rats with IDA up to a level of healthy animals. However, recovery of number of sulphite-reductive clostridia in anemic animals’ gut, which had been receiving FeNPs, was more effective than in the case of comparison drug administration. FeNPs are possessed by favourable effect on the gastrointestinal tract microflora in case of IDA. Therefore, FeNPs are perspective as biosafe and biocompatible pharmacological substance for development of new class antianemic preparations.

Key words: iron nanoparticles, anemia, iron deficiency, dysbacteriosis, intestinal microflora, normalization.

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References

 
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IMMUNOMORPHOLOGICAL AND MORPHOMETRIC CHARACTERIZATION OF CENTRAL AND PERIPHERAL ORGANS OF IMMUNOGENESIS IN MICE UNDER PUTRESCINE ADMINISTRATION TO EXPERIMENTAL ANIMALS

Authors: Zilfyan A.V., Avagyan S.A. 

Pages: 300-307

Abstract

  

We studied the influence of exogenously administered putrescine on morphofunctional state of the central and peripheral organs of immunogenesis of experimental animals. White mice were exposed to single intravascular administration of putrescine (Sigma, USA) at a concentration of 10-9 mg/mL per 100 g animal body weight. Animals were euthanized in 2 and 8 hours after putrescine administration observing all standards set forth by the Yerevan State Medical University (YSMU) Committee on Bioethics for investigations involving laboratory animals.

Structural changes corresponding to the notion of “accidental involution” occurred in the cortical layer of thymus in experimental animals 8 hours after putrescine administration. Structural shifts manifested as a targeted activation of B-dependent zones and layers were observed in spleen and lymph nodes. The performed immunomorphological studies revealed that activation of B-dependent zones expresses a marked increase in number of B-lymphocytes containing IgG, as well as an increase of IL-1α content in these cells. It is not excluded that putrescine at rather low concentrations (similar to those determined in blood serum of intact mammals) in spleen and lymph nodes exerts targeted immunomodulating action and selectively activates B-lymphocytes populations, which, in turn, are responsible for activation of humoral immunity reactions.

Key words: putrescine, organs of immunogenesis, structural shifts, B-lymphocytes, interleukin 1 α, immunomodulation.

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STUDYING OF REPARATIVE PROPERTIES OF A NEW COMBINED OINTMENT ON THERMAL BURN MODELS IN RATS

Authors: Tsulun O.V. 

Pages: 308-315

Abstract

  

Introduction. Burn can be defined as a tissue damage caused by a variety of agents such as heat, chemicals, electricity, sunlight, or nuclear radiation. Treatment of burns has an important medico-social significance in order to speed up the recovery of injured people and return them working ability. One of perspective directions is to create preparations that possess antioxidant properties, have sufficient reparative anti-inflammatory effect, and are safe.

My aim is to assess the effect of a topical ointment with licorice extract, coenzyme Q10 and dihydroquercetin (further mentioned as LCD ointment) on healing of partial thickness burn wounds in rats.

Material and Methods. Burns were modeled on 20 albino rats, weighting 260–300 g under ketamine (100 mg/kg) anesthesia by pouring hot molten wax at 80°C into pattern of 4 cm2 placed on depilated skin on one side of the animals. Rats were divided into four groups: group 1 – control group; group 2 – treated with LCD ointment; group 3 – treated with methyluracil ointment (reference-drug); group 4 – treated with ointment containing rutin, coenzyme Q10 and licorice extract (further mentioned as LCR ointment). Ointments were applied topically once a day. I performed evaluation by measuring wound contraction and recording the period of epithelialization.

Results and Discussion. Topical application of ointments LCD and LCR enhanced significantly healing of burn wounds. The mean period of epithelialization was significantly reduced in topical LCD ointment (by 31.5%) group and LCR ointment (by 20.4%) group as compared to the control.

Conclusion. I established that ointments LCD and LCR promoted healing of burns and exhibited evident reparative activity on the model of wax-induced burn wounds in rats. Ointments LCD and LCR reduced epithelialization period by 6.8 and 4.4 days respectively, compared to the control group. Planimetric parameters showed that burn area decreased by 63.5% on day 5 and by 98.2% on day 15 in LCD treated group; in LCR ointment group percentages of wound contraction were 44.6% and 94% respectively, which exceeded reference-drug. Therefore, ointments LCD and LCR have expressed reparative activity; they can become promising drugs for further pharmacological studies to use in clinical practice.

Key words: dihydroquercetin, licorice extract, thermal burn, reparative properties, ointment.

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CEREBROSPINAL FLUID AS AN ENVIRONMENT WITH RADIOPROTECTIVE PROPERTIES

Authors: Absettarova A.I., Kakura S.I., Oleynikova O.K.Pikaluk V.S.Bessalova Ye.Yu. 

Pages: 316-322

Abstract

  

Our aim is to analyze a xenogenic cerebrospinal fluid as radioprotectivebiological substrate. The article is devoted to revealing and studying of the morphological changes of the irradiated Wistar rats' bone marrow, blood, hypophysis and peripheral glands after parenteral injection of xenogenic cerebrospinal fluid in different periods of postnatal development (newborn, immature, mature). Lactating cows aged 4–6 years were taken as cerebrospinal fluid donors. We studied the effect of cerebrospinal fluid using certain anatomical and histological methods.

It was found out that cerebrospinal fluid preparation caused different inhibiting effects on destructive processes in cells of some organs; it is associated with the presence of broad spectrum of biological active substances in mammalian cerebrospinal fluid. The evident radioprotective effect was proved by the analyses of the destructive processes degree in red bone marrow cells of the rats exposed to total body radiation at 5 Gr and 3- and 10-times infusions of cerebrospinal fluid. Findings testify to activating of regenerator and strengthening processes of all sprouts of red marrow at the correction of consequences of irradiation by introduction of cerebrospinal fluid. However, the least degree of expression of these processes is noticed in the old age group: there is, probably, cerebrospinal fluid with the decline of activity of adaptation mechanisms. Morphofunctional indexes and age-dependent dynamics were revealed using white rats after xenogenic CSF parenteral injections at various ontogenetic periods.

Nowadays, cerebrospinal fluid is considered to be a morphological substrate at the homeostasis anatomophysiological component; it also participates in the intersystemic nervous and endocrine regulation. These facts allow us to formulate a new scientific conception of xenogenic cerebrospinal fluid morphophysiological regulatory effects. That provides their systemic cognition at leading intention to disclose liquor’s regulatory physiological role at an organism. Considering none immunopathological response onto injection of cerebrospinal fluid and the complex assessment of its anatomophysiological effects, we set up challenging perspectives to develop a directional bioactive drug based on cow’s cerebrospinal fluid. This drug can be applied in fields of medical and veterinary science, animal breeding and experimental morphology.

Key words: cerebrospinal fluid, radiation, bone marrow, nervous, endocrine, immune regulation.

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SHIFTS IN CONTENT OF INTERLEUKINS IL-1 alpha, IL-2, IL-6 AND gamma-INTERFERON, PROLACTIN AND INSULIN-LIKE GROWTH FACTOR IN ORGANS OF IMMUNOGENESIS UNDER THE CONDITIONS OF PUTRESCINE ADMINISTRATION TO EXPERIMENTAL ANIMALS

Authors: Zilfyan A. V.,Avagyan S. A. 

Pages: 323-330

Abstract

  

Method of immune enzyme assay (ELISA) was employed to study the shifts in content of immunocytokines, prolactin, and insulin-like growth factor-1 in the central and peripheral organs of immunogenesis in mice. Single intravascular administration of putrescine was performed at rather low doses similar to levels determined in blood serum of small laboratory animals (rats and mice). Animals were euthanized by decapitation under the Nembutal narcosis in accordance with the strict requirements of Yerevan State Medical University (YSMU) Committee on Bioethics for investigations involving laboratory animals.

Shifts revealed in thymus of experimental animals signified putrescine-dependent immune-suppressive effect regarding the selective inhibition of IL-2, IL-6 and γ-IFN synthesis in the central organs of immunity. High indices of IL-1a, IL-6 and prolactin were recorded in the spleen and nodes of experimental animals 8 hours after the putrescine administration. It is not excluded that under conditions of our experiment, IL-6 high levels in spleen and lymph nodes were also conditioned by stimulant effect of prolactin towards B-lymphocytes populations (this effect is induced by relatively high levels of prolactin); besides that, similar mechanism of prolactin direct stimulating influence on B-lymphocytes in the aspect of IL-1a synthesis by B-lymphocytes is described in the literature.

It is also known that the enhanced synthesis of γ-IFN in immunocompetent cells is accompanied with the marked activation of specific T-lymphocytes sub-populations: T-suppressors and T-killers possessing the cytotoxic activity. Therefore, we might make an assumption: exogenous putrescine administered by us to the animal organism at rather low concentrations directly and/or indirectly inhibits the activity of cytotoxic T-lymphocytes sub-populations.

Key words: putrescine, organs of immunogenesis, B-lymphocytes, immunocytokines, prolactin, immunomodulation.

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CYSTATIN C – A MARKER OF RENAL AND MYOCARDIAL DYSFUNCTIONS IN PATIENTS WITH ISCHEMIC HEART DISEASE ASSOCIATED WITH INITIAL STAGES OF CHRONIC KIDNEY DISEASE

Authors: Kravchun P.G., Mykhailova Yu.O., Lapsina L.A.

Pages: 331-338

Abstract

  

Introduction. Renal dysfunction in patients with chronic heart failure (CHF) plays a key role as a risk factor and predictor of unfavorable prognosis, marker of increasing the frequency of hospitalizations and deaths. In recent years cystatin C as a marker of early diagnosis of glomerular functions, staging and prognosis of chronic kidney disease (CKD) is often used for assessment of renal function. There are a lot of publications about the role of cystatin C as an independent biomarker of cardiovascular events, including myocardial dysfunction in patients without primary renal impairment.

Our aim was to access the cardiorenal interactions in patients with CHF associated with CKD I–II stage by determining the levels of cystatin C.

Material and Methods. We examined 103 patients with CHF. 58 patients with CHF and CKD comprised group 1; group 2 – 45 patients with CHF without CKD. Serum creatinine was measured by Jaffe-method, the levels of cystatin C – by ELISA, glomerular filtration rate (GFR) was calculated by MDRD formula; also used echocardiography, kidneys ultrasound.

Discussion. We determined the increase of creatinine levels in patients with CHF and CKD in 58 % cases, cystatin C – in 78 % cases; the decrease of GFR – in 76.1 % cases, in patients with CHF without CKD – in 42 %, 64 % and 68.9 % cases respectively.

The increase of cystatin C levels was more significant than the classical indicators of glomerular function (creatinine and GFR) in patients with CHF and CKD and without CKD in general groups, also in such subgroups as: 1) patients with preserved systolic function (ejection fraction>45%) and systolic dysfunction (ejection fraction≤45%), 2) patients with presence of left ventricular hypertrophy, 3) with normal values of GFR (GFR ≥ 90 ml/min/1.73 m2) and a moderate decline of GFR (GFR ≤ 89 ml/min/1.73 m2). Thus, cystatin C can be considered as an earlier marker of renal function disorders. We found correlations between ejection fraction and left ventricular mass index with cystatin C. Perhaps, cystatin C contributes to formation of hemodynamic disturbances. Early stages of CKD in patients with CHF potentiate disorders of renal function and play the role as an additional risk factor forprogression of heart failure.

Assessment of cystatin C in CHF with CKD and without CKD patients can help doctors in daily practice to improve the quality of early diagnosis and prognosis.

Key words: chronic heart failure, chronic kidney disease I - II stage, cystatin C, glomerular filtration rate (MDRD), creatinine.

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References

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CONTENTS OF COBALT, NICKEL AND LEAD IN THE “MOTHER-PLACENTA-FETUS-NEWBORN” SYSTEM UNDER PHYSIOLOGICAL CONDITIONS

Authors: Tarasova I.V., Turova L.O., Kasian S.M., Shvydun K.O. 

Pages: 339-345

Abstract

  

Our aims was to study the contents of trace elements (Co, Ni, Pb) in biological fluid of the pregnant women and newborns. The objects of investigation were 30 women with physiological pregnancy and 30 healthy full-term newborns. We measured levels of these trace elements in the serum, erythrocytes, cord blood and placenta. The content and balance of microelements were analyzed by the atomic absorption spectrophotometry method using aspectrophotometer C 15-M1 with a flame atomizer(“Selmi”, Ukraine).We also characterized the features of transplacental migration of these micronutrients to a fetus. We studied the placenta barrier function and deposition of cobalt, nickel and lead. Our research proved that lead retained less in the placenta of a pregnant woman than nickel. Thus, nickel can be more vulnerable to the fetus, because of its toxic effect during the prenatal period. We also reported that placenta plays an important role in balance of trace elements in the fetus; it performs a barrier and depot functions. Unfortunately, the placenta barrier function is relatively weak against lead, nickel and cobalt. Although, the placenta can accumulate a greater amount of nickel (accumulation index – 275.8 %) than lead (accumulation index – 204.0 %) and, especially, cobalt (accumulation index – 121.2 %).

Key words: placenta, fetus, full-term newborn.

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References

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THE PREVALENCE OF RISK FACTORS AMONG INFERTILE COUPLES IN THE CHERNIVETSKY REGION OVER TIME

Authors: Tymchenko O.I., Koba O.P., Mykytenko D.O., Maksiyan O.I., Lynchak O.V.

Pages: 346-352

Abstract

  

Introduction. In conditions of decreasing birthrate, the infertile couples as well as couples with reproductive losses could be as a reserve of increasing birthrate. These families want, but cannot have got their own children. A sequential detection and study of complex cases and mechanisms of infertility development allows us to determine the exact individual strategy of treatment. In the same time, the measures of primary prevention (based on the prevention of negative influence of different risk factors) are efficient on a population level. Even in a case of reproductive clinics activity, the prevention measures on a primary stage of pregnancy planning are necessary and urgent. Many factors, which could be important in human pathology development, should be taken into account in order to prognostication of individual reproductive health status. That is why process of regional investigation results extrapolation to the other regions without analysis of their features is inadequate and ineffective.

The aim is to determine the infertility development risk factors prevalence between people of the Chernivetsky region over time.

Material and Methods. The primary materials were 273 special registration cards for cases of infertile couples in the Chernivetsky region (in 1999–2003 and 2012–2013).The cases of healthy children birth were taken as control (1010). The risk was calculated as Odds Ratio indicator, including 95 % confidence interval. The infertility risk factors prevalence was determined by comparison of infertile couples percentage in 1999–2003 and 2012–2013. The critical level of statistical criterions was accepted as P ≤ 0.05.

Discussion. In 1999–2003 the main infertility risk factors were chronic female and male infections (OR = 4.02 95%CI:3.35–4.82 and 4.82 95%CI:4.18–5.61 accordingly). In comparison with 1999–2003 / 2012–2013, we noticed the absence of differences in prevalence of extragenital and endocrine pathology, chronic infections, professional risks as well as smoking between infertile couples. Over time between infertile women and men, we detected increasing of educational level and fraction of unemployed individuals. Moreover, 7-time increasing of fraction of couples, who used paid medical services, was shown as well as 4-time increasing of fraction of couples, whose total income allows them to use paid medical services.

Key words: infertility, married couples, risk factors.

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References

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THE IMPACT OF SOCIAL AND ECONOMIC FACTORS OF PATIENTS ON THEIR ADHERENCE TO MEDICATIONS AFTER ISCHEMIC HEART DISEASE IN AL-NAJAF CITY

Authors: Diaa Kareem Abd-Ali, Halima Yusuf Al-Rubaiyee

Pages: 353-364

Abstract

  

Cardiovascular disease (CVD) remains a global health problem that affects millions of people worldwide. This disease affects people at all ages; it's not a disease of the elderly. Thus, this study is conducted to establish a data base for the patient adherence to medications and the impact of social and economic factors on such adherence after ischemic heart disease in Al-Najaf City.

Our aim was to assess patients’ adherence to medications after ischemic heart disease (IHD), to assess the social and economic factors of the patients, which may affect their adherence to medications, and to find out the impact of social and economic factors on patients’ adherence to medications.

Material and Method. We carried out a cross-sectional study in Al-Najaf Health Directorate, Al-Sadder Medical City and Al-Najaf Center for Heart Diseases and Surgery from June 5, 2013 to April 10, 2014. A non-probability sampling (purposive sample) of 102 patients diagnosed medically as the ischemic heart disease patients (angina and myocardial infarction) were included in the study. We collected the data using the semi-structured questionnaire, which consisted of three parts: 1) socio-demographic and clinical data form; 2) patient adherence to medications scale; 3) socioeconomic factors of a patient. The data were described statistically and analyzed using the descriptive and inferential statistical analyses.

Results and Discussion. Our results reveled a deficient in the patients’ adherence to medications. Moreover, there was a significant impact of the social and economic factors on the patients’ adherence to medications after ischemic heart disease.

Conclusion. We found a deficient in the patients’ adherence to therapeutic recommendations, specifically to medications use. Certain defects were with the social and economic factors, which could enhance the patient adherence to medications. The intensive comprehensive wide population-based studies should be conducted to assess the factors, which affect the patient adherence to medications after the IHD suggesting a suitable solution for these factors to improve the level of patient adherence. The health education program should be implemented to increase patients’ knowledge about importance of adherence to medications, certain factors that may affect their adherence, and possible ways to solve this problem.

Key words: impact, patient adherence, ischemic heart disease.

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MEDICAL AND PSYCHOLOGICAL FEATURES OF QUALITY OF LIFE OF YOUNG ADULTS AFTER CONGENITAL HEART SURGERY

Authors: Kasianova A.Yu., Lebid I.G.

Pages: 365-372

Abstract


Modern cardiosurgery opportunities of highly qualified specialists can help patients with congenital heart disease (CHD) to improve significantly their health and life longevity, but at the same time, many patients still complain of weakness, fast tiredness, bad mood and low quality of life.

Our aims was to identify medical and psychological features of low quality of life of adult patients of younger age after congenital heart surgery.

Material and Methods. The study involved patients (aged 19 ± 2.8 years) with surgically corrected inborn congenital heart disease. The psychodiagnostics included the study of the quality of life and the identification of signs of anxiety and depression in the patients.
Discussion. We identified gender differences in the quality of life of young adult patients with CHD: namely, every day activities of men were significantly limited due to their physical condition, – it either precedes or follows the worsening of their emotional status – but women had rather high indices of life quality. However, both men and women displayed a dramatic limitation of social contacts. Young adult patients with surgically corrected CHD displayed significant limitation of social contacts, decrease in communication levels due to the worsening of their physical and emotional condition. 42 % of male and 50 % of female patients displayed the symptoms of anxiety and/or depressive disorders.

Conclusion. Having analyzed practical advantages and possible disadvantages of different foreign questionnaires, which are adapted in Russian to assess the quality of life, we found out that MHFLQ (Minnesota Living with Heart Failure Questionnaire) is very simple and easy to use in individual analysis. However, it does not allow us to differentiate the calculation of component parts of mental, physical and social functioning for a specific group of patients. At the same time, the MOS SF-36 (36-Item Short Form Health Survey) and WHOQoL-bref (World Health Organization Quality of Life) methods allow us to assess a specific influence of physical, mental and social components on the quality of life. Unfortunately, these surveys have displayed different results. The HADS (Hospital Anxiety Depression Scale) method provides an opportunity to single out a patients’ risk group characterized by a clinical level of depression and anxiety. The implementation of active and timely psychodiagnostics and psychocorrection measures will help adult patients with the inborn congenital heart disease after the surgery to improve their quality of life.

Key words: congenital heart disease, adult patients, cardiosurgery, quality of life, anxiety, depression.

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ASSOCIATION BETWEEN HYPOVITAMINOSIS D AND METABOLIC SYNDROME IN OBESE PATIENTS WITH CORONARY HEART DISEASE

Authors: Orlovskyi V.F, Hordina M.A., Orlovskyi O.V., Skoropad Yu.I.

Pages: 373-380

Abstract


Introduction. Metabolic syndrome(MS) is a problem of the 21st century in industrialized countries. Hypovitaminosis D is a risk factor, which may cause development of metabolic disorders. D-deficiency is usually registered in obese patients. Our aim was to find the association between metabolic syndrome and vitamin D levels in obese patients.

Material and Methods. We examined 62 obese patients with coronary heart disease: 33 patients with MS (aged 63.9 ± 1.69 years with BMI 35.1 ± 0.59 kg/m2) and 29 without MS (aged 66.9± 2.25, (p >0,05); with BMI 34.9 ± 0.57kg/m2). 25(OH) vitamin D3 levels were measured by the immunoassay analysis. Insulin resistance was estimated by fasting blood insulin, HOMA-IRQUCKI and НОМА%S.

Discussion. Serum 25(OH)D3 levels were significantly lower in MS obese patients than in obese patients without MS (39.2 ± 2.11 vs 46.5 ± 2.97, p < 0.05). The low 25(OH)D3 levels correlated with BMI, total cholesterol, triglycerides, high and low density lipoproteins, insulin, and HOMA-IR (p<0.05). After stratifying the study population according to 25(OH)D3 concentrations, patients in the lowest quartile showed a markedly increased prevalence of MS compared with those in the highest quartile (68.8 vs 25 %). Using the one way analysis of variance (ANOVA), we revealed that patients in quartile IV (with the highest 25(OH)D plasma level (53.9–70.7 nmol/l)) had significantly lower blood glucose (p = 0,007) and fasting insulin (p < 0.001). Moreover, there was better performance sensitivity of peripheral tissues insulin that is likely to lower the level of HOMA-IR index and raise the QUCKI index (p < 0.001). They also maintained a more favorable performance lipids levels: significantly lower concentrations of total cholesterol (p < 0.001), triglycerides (p < 0.001), but higher HDL levels (p = 0.020). We did not find any significant difference between quartiles I and IV for anthropometric indicators, as well as HOMA%S.

Conclusion. A strong association exists between hypovitaminosis D and MS in obese patients independently/disregarding / from BMI and waist circumference. This indicates that the association between low 25(OH)D levels and MS is not merely induced by vitamin D deposition in fat tissue and hypovitaminosis D in patients with obesity may contribute to the development of metabolic changes, such as atherogenic dyslipidemia and insulin resistance that are components of MS.

Key words: vitamin D, obesity, metabolic syndrome, insulin resistance.

mgordina@yandex.ru

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EVALUATION OF THE EFFECTIVENESS OF SURGICAL TREATMENT OF BENIGN BREAST DISEASES

Authors: Yazykov O.V., Leonov V.V.

Pages: 381-389

Abstract


Introduction. Up to 70 % of the female population of Ukraine has benign breast diseases, so it is extremely important to treat these patients. We know that sector resection of breast is aimed at the elimination of pathologically altered focus, but this method does not provide satisfactory aesthetic results. Scar deformation of the breast, the loss of its natural appearance after surgery significantly reduces the quality of life of patients, which can be a convincing evidence of the low efficiency of sector resection.

Our aim is to analyze the effectiveness of breast benign surgery using traditional and modified techniques.

Material  and Methods. We studied the results of treatment of 151 patients with benign breast diseases: 106 women were operated using the developed methods, sector resection of the breast was performed on 45 patients performed. We used the instruments SF-36v2TM to assess quality of life; we used BEQ before surgery, in 3 and 12 months after surgery to assess the aesthetic satisfaction tool. We estimated radicality and validity of operations from the results of histological examination of removed tissue.

Discussion. The analysis of questionnaires for three observation periods revealed that sector resection of the breast did not change the health-related quality of life of patients (51.9 and 46.08 vs. 50.8 and 47.75 points before surgery for PCS and MCS, respectively (MID ˂ 2). At the same time, a significant negative impact on the aesthetic component of quality of life made the results of surgical treatment unsatisfactory. However, the developed operations enhanced health-related quality of life of patients in a year (53.7 and 53.8 vs. 51.01 and 43.57 points before surgery for PCS and MCS respectively, p = 0.01; MID ˃ 2). For instance, significantly increased the satisfaction of the aesthetic state of breast (3.82 and 3.78 vs. 3.58 and 3.53 points before surgery for satisfaction with attributes level of self-confidence, p ˂ 0.05). Polycystic breast lesions in more than 20 % of cases expressed proliferative and degenerative changes. Therefore, the maximum removal of tissue is the prevention of breast cancer. Due to the high probability of dysplastic changes in fibroadenomas in patients older than 35 years (10 %), we believe that observation and conservative treatment is unacceptable.

Key words: breast benign lesions, mini-invasive operations, plastic and reconstructive surgery, quality of life.

yazikov@i.ua

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ALLELIC CONDITION OF GENE PPAR-GAMMA2, ACE IN PATIENTS WITH ARTERIAL HYPERTENSION AND ABDOMINAL OBESITY

Authors: Sokolenko A.A., Sydorchuk L.P., Sokolenko M.O.

Pages: s1-s12

Abstract

  

Introduction. Abdominal obesity (AO) is one of the major independent risk factors of arterial hypertension (AH). AH and AO are multifactorial polygenic diseases. The peroxisome proliferator activated by gamma 2 receptor (PPAR-g2) plays a pivotal role in the lipid metabolism. PPAR receptors modulate the activity of the renin-angiotensin-aldosterone system (RAAS) through transcriptional control of the synthesis of renin, angiotensin, angiotensin-converting enzyme (ACE) and angiotensin II receptor type 1, linking biological effects of RAAS and PPARs. Therefore, the study of genes polymorphism PPAR-γ2 receptor and ACE allows us to explore in detail their role in the pathogenesis of AH and AO.

Our aim was to analyze the frequency of alleles and genotypes of Pro12Ala polymorphism of PPAR--g2 gene (rs1801282) and I/D polymorphism of ACE gene (rs4646994) in patients with essential AH (EAH) combined with overweight or AO.

Material and Methods. 110 screened patients with EAH I–III stages participated in a prospective study: 56.4 % women, 43.6 % men; mean age – 53.3 ± 6.05 years. Among them we revealed EAH I in 22.7 % cases, EAH II – in 45.45 %, EAG III – 31.8 %; overweight persons – 38.2 %, with AO – 53.6 %. The control group included 50 healthy individuals. Alleles of polymorphic locus were studied by polymerase chain reaction based method. Statistical processing was performed usingthe Statistica® 7.0 software. The differences were considered significant at p < 0.05.

Results. The DD-genotype of ACE gene in EAH patients is observed in 39.1 % cases, which is 2.2 times more than in the control group. In patients with EAH dominated "unfavorable" D allele. DD-genotype is associated with a greater frequency of concomitant coronary artery disease, cerebrovascular disease, left ventricle hypertrophy (LVH) in women, higher levels of systolic blood pressure (SBP), and obliterative arterial disease of lower extremities (OADVE).

ProPro-genotype of PPAR-g2 gene was found in 63.6 % cases, which generally does not differ from the control group (60.0 %). Among patients with EAH dominates Pro-allele by 3.9 times (79.5 % vs. 20.4 % Ala-allele carriers), likewise in the control group by 3.5 times (78.0 % vs. 22.0 %), respectively. ProPro-genotype in patients with EAH associated with significantly more frequent cases of diabetes mellitus type 2, AO, LVH in men, OADVE, inherited AO, higher SBP, diastolic BP, and waist circumferences in men. In patients with EAH I dominates I-allele of ACE gene by 3.8 and 3.23 times and ProPro-genotype of PPAR-g2 gene over AlaAla-genotype by 4.67 and 14 times. Exclusively D-allele and Pro-allele carriers were available among patients with EAH III stage. In patients with EAH with normal body weight and AO 1st degree II genotype prevails over DD-option by 2 and 4 times, respectively. In those with overweight, AO 2nd degree the ProPro-genotype dominated the AlaAla-genotype by 12–17 times; among those with overweight available only D-allele carriers; in patients with EAH AO 3rd degree – there are only ProPro-carriers.

Conclusion. DD-genotype or D-allele of ACE gene is a risk factor for EAH II and III stages (OR = 2.33–4.45, p ≤ 0.014–0.013), excess body weight (OR = 4.10–4.45, p < 0.001), AO (OR = 4.45, p < 0.001) with the lowest probability of EAH I stage (OR = 0.22, p = 0.007).

Key words: arterial hypertension, abdominal obesity, АСЕ gene (I/D), PPAR-g2 (Pro12Ala).

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STUDY OF ENOS GENE EXPRESSION IN PLACENTAL TISSUE DURING IRON DEFICIENCY ANEMIA

Authors: Ancheva I.A. 

Pages: s13-s19

Abstract


Introduction. One ofthe mosturgent problemsof modern obstetricsis the occurrenceof iron deficiencyin pregnant women. The experts assess its prevalence in 20–30 % ofcasesin economicallydeveloped countriesand50–80 % – in developing countries.InUkrainein the recent years,the incidenceof iron deficiency anemia during pregnancy increased from15.0 to 22.6 %. The interest ofresearchersto the problemof IDAdue to the factthat inthispathological conditionincidenceof preeclampsia,preterm labor, polyhydramnios, prematurerupture of membranes,weakness of laborforces and otherpregnancy complicationssignificantly increased.According toexperts, theincrease in the amountof blood lossduring laboris in 10 % ofpregnant women withIDA.This populationof pregnant womenhasalsopostpartumseptic complicationsandhypogalactia. Iron deficiency significantly worsensoverall condition of mother and fetus.

Our aim was to evaluate the gene expression of eNOS in placental tissue of the pregnant women with iron deficiency anemia.

Material and Methods. Research performed at the maternity hospital № 2 (Odessa), Genetic Laboratories "Nadiaya" and pathomorphological department of State Institution "IPOG NAMSU" (Head, Professor, MD Zadorozhna TD, Kyiv). The study involved 100 women in labor; we took placenta samples from them. Thus, the following clinical groups were designed: group 1 – the placenta samples of women with physiological pregnancy and childbirth (n = 20), group 2 – the placenta samples of pregnant women with a history of anemia (n = 40), group 3 – the placenta of women with placental dysfunction and a history of anemia (n = 40). In addition to the general clinical research methods, we used current clinical protocol approved by the order № 782 dated 29.12.2005 “On approval of clinical protocols for obstetric and gynecological care”, further research was conducted analysis of immunohistochemical expression of endothelial nitric synthase (eNOS) in placental tissue. Age of pregnant women ranged from 20 to 35 years (28.5 ± 2.8 years).

Discussion. As a result the level of eNOS gene expression increased by 1.4 folds in patients with IDA, while the combination of IDA and placental dysfunction eNOS gene expression level reduced by 10 folds. We discuss the adaptive nature of changes in eNOS gene expression in iron deficiency amongst pregnant women. There were compared genetic and phenotypic characteristics of the enzyme activity of endothelial nitric oxide synthase in decidual tissue. When comparing detected changes of eNOS gene expression with the phenotypic manifestations we found that the expression of endothelial nitric oxide synthase in patients with dysfunction of the placenta in the cytoplasm synticia villi and fetal capillary endothelium and vascular decidua reduced, and the presence of a combination of placental dysfunction and iron deficiency anemia occured with the paradoxical increase expression of the enzyme. Thus, inhibition of eNOS gene expression is a reflection of the exhaustion of the adaptive capacity of the organism. This circumstance suggests that routine administration of nitric oxide precursor (L-arginine medication) in women with gestational endoteliopatiyi manifestations may not give the desired effect due to the presence of a genetically determined deficiency of endothelial nitric oxide synthase and its products. Besides, when isolated iron deficiency anemia occurs than changes in eNOS gene expression is less evident.

Key words: iron deficiency anemia, pregnancy, nitric oxide synthase, genetics.

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АNALYSIS OF THE EFFECT OF BONE MORPHOGENETIC PROTEIN-2 (BMP-2) GENE SER37ALA POLYMORPHISM ON SOME CHARACTERISTICS OF THE ACUTE CORONARY SYNDROME

Authors: Garbuzova V.Yu. 

Pages: s20-s28

Abstract


 

Introduction. BMP-2, like other bone morphogenetic proteins, plays an important role in the development of bone and cartilage, in osteoblast differentiation. As the calcification of the atherosclerotic plaque is an untoward prognostic factor of the acute coronary syndrome, the polymorphism of gene BMP-2 can be associated with the disease progression.

The aim isto establish the association of allelic variants of BMP-2 gene Ser37Ala polymorphism on some characteristics of the acute coronary syndrome (clinical variants, ECG manifestations, development of complications).

Material and Methods. We used venous blood of 118 patients with ACS (22 % women and 78 % men) aged 40 to 73 years (mean age 55.9 ± 0.89 years) hospitalized in the cardiology department of Sumy City Clinical Hospital № 1. The control group consisted of 234 patients. I performed definition of Ser37Ala polymorphism (rs2273073) of BMP-2 gene using PCR with the following restriction fragment length analysis of the allocation of them by electrophoresis in agarose gel. Restriction endonuclease Hpy99I was used for restriction analysis. Statistical analysis was performed by using the software package SPSS-17. Thus, the significance of differences was determined by the χ2-criterion. The value of P < 0.05 was considered as significant.

Results. There isn’t significant difference in the ratio of genotypes (Ser/Ser, Ser/Ala, Ala/Ala) between patients with anginal form of acute coronary syndrome (ACS) and patients with other forms of ACS (аsthmatic, abdominal, arhythmic and painless). It accounted for 51.5; 30.1 and 18.4 % in the group with anginal form of ACS; and 40.0, 46.7 and 13.3 % – in the group with other forms of ACS. Using the χ2-Pearson criterion, it did not reveal association between the Ser37Ala polymorphism of ВМР-2 gene and the clinical variants of ACS (χ= 1.652, Р = 0.438). Analysis of the data about correlation Ser37Ala polymorphism of BMP-2 gene with different clinical variants of ACS showed no association of investigated SNP with different clinical manifestations of this disease (unstable angina, non-Q-myocardial infarction, Q-and QS-myocardial infarction). There is no veracity in the distribution of genotypes considering such risk factors as gender, BMI, hypertension, lipid composition and blood hypercoagulation, diabetes, and obesity. The difference of allelic variants frequency was statistically significant (P = 0.033) in groups with different clinical forms of ACS only in patients, who smoke. Smokers with Ser/Ser genotype were significantly more likely to develop anginal form of ACS. Significant difference in the distribution of patients with unstable angina, non-Q-myocardial infarction, Q-and QS-myocardial infarction was found only in patients with obesity (P = 0.018). I did not find significant difference in the distribution of genotypes between patients with complications and those who have had the disease without complications. However, the association with the development of complications of ACS was for male patients, smokers, patients without DAC and without obesity.

Ambiguity and deficiency of data about relationship Ser37Ala and other polymorphisms of BMP-2 gene with the development of ACS requires further research in this area.

Conclusion: Smoking patients with Ser/Ser genotype BMP-2 gene Ser37Ala polymorphism are significantly more likely to develop anginal form of ACS.

There is significant difference in the distribution of genotypes among individuals with unstable angina, non-Q-myocardial infarction, Q-and QS-myocardial infarction in the group without obesity.

There is a link with the development of complications of ACS for male patients, smokers, patients without atherogenic dislipoproteinemia and without obesity.

Key words: allelic polymorphism, bone morphogenetic protein-2, acute coronary syndrome.

vikgarbuzova@yandex.ru 

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CYTOKINES GENES POLYMORPHISM IN PATIENTS WITH HIV INFECTION

Authors: Piddubna A.I., Chemych M.D.

Pages: s29-s37

Abstract


Our aim was to study distribution character of the allelic variants of cytokines genes in HIV-infected Ukrainians.

Data for the study were DNA samples, received from 200 inhabitants of Ukraine: 78 HIV-infected, 22 HIV-negative individuals from the group of high risk of contamination, 100 healthy blood donors. IL-4 (-590C/T), IL-10 (-592C/A) andTNF-α (-308G/A) genes polymorphisms detection was made with the PCR-RLFP method.

By analysis of frequency of IL-4 gene allelic variants, we discovered that homozygotes by the main allel were the dominant variant. Among people with HIV T/T minor gene carriers were 4.5 more often met in comparison with the control group (p < 0.05) that can prove the tendency to association of the mentioned genotype with infection. Distribution of allelic variants of IL-10 gene promoter region in position -592 is characterized by homozygote dominance by the main gene. Among the individuals with HIV A/A minor allel carriers were 3.4 more often than in the control group (p < 0.05). Individuals with A/A genotype were not identified in group of high risk of virus infection. The abovementioned proves the tendency to association of minor allel carrier state with HIV infection. Theoccurrenceofthehomozygouscombinationoftheallelicvariant G/GofthepromoterofTNF-αis provedtoprevailalmosttwofoldovertheoccurrenceofthevariantG/Aamong all groups. High frequency of heterozygote by the main allel was recorded among the individuals with HIV. Thus, G/A genotype frequency in group of HIV-infected people by 2 and 1.5 times exceeded the appropriate indices of group of high risk of infection and comparison group correspondingly (p < 0.05) that points on the tendency to association of the mentioned variant with infection. We concluded that cytokines genes variationsmaycontributetotheacquisitionofHIVinfectionin the Ukrainians andencourages carrying out further populations studies in this sphere of HIV-infection immunogenetics.

Key words: HIV infection, cytokines, allelic polymorphism.

tranki1@mail.ru

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ASSOCIATION OF K121Q POLYMORPHISM ECTONUCLEOTIDE PYROPHOSPHATASE/PHOSPHODIESTERASE 1 (ENPPI) GENE WITH ACUTE CORONARY SYNDROME IN PERSONS OF DIFFERENT SEXES

Authors: Rozymenko I.A. 

Pages: s38-s44

Abstract


Introduction. Ectonucleotide pyrophosphatase/phosphodiesterase family member 1 is an enzyme, which is encoded by the ENPP1 gene in humans. This gene is a member of the ecto-nucleotide pyrophosphatase/phosphodiesterase (ENPP) family. The encoded protein is a type II transmembrane glycoprotein comprising two identical disulfide-bonded subunits. This protein has broad specificity and cleaves a variety of substrates, including phosphodiester bonds of nucleotides and nucleotide sugars and pyrophosphate bonds of nucleotides and nucleotide sugars. This protein may function to hydrolyze nucleoside 5' triphosphates to their corresponding monophosphates and may also hydrolyze diadenosine polyphosphates. Mutations in this gene have been associated with іdiopathic infantile arterial calcification, ossification of the posterior longitudinal ligament of the spine, insulin resistance. As the calcification of the atherosclerotic plaque is an untoward prognostic factor of the acute coronary syndrome, the polymorphism of gene ENPP1 can be associated with the disease progression.

The aim was to establish the frequency of allelic variants of the ENPPI gene for K121Q polymorphism in patients of different sexes with acute coronary syndrome (ACS).

Material and Methods. We used venous blood of 118 patients with ACS (22 % women and 78 % men) aged 40 to 73 years (mean age 55.9 ± 0.89 years) who were hospitalized in the cardiology department of Sumy City Clinical Hospital № 1. The control group consisted of 110 patients. Definition of K121Q polymorphism (rs1044498) of ENPPI gene was performed using PCR with the following restriction fragment length analysis of the allocation of them by electrophoresis in agarose gel. Restriction endonuclease Eco47I (AvaII) was used for restriction analysis. Statistical analysis was performed using the software package SPSS-17. Thus, the significance of differences was determined by the χ2-criterion. The value of P < 0.05 was considered as significant.

Results. Using the χ2-Pearson criterion, I did not reveal association between the K121Q polymorphism of ENPPI gene and the development of ACS. Distribution of different types of genotype between patients with ACS and healthy patients did not differ statistically significantly. I pointed out that in patients with ACS value homozygotes for the major allele (K/K) and minor allele carriers (K/Q + Q/Q) were 66.9 and 33.1 %, while in the control group –75.5 and 24.5 %, respectively. Factor P, defined by χ2-Pearson criterion, was equal to 0.157 and indicated a lack of significant difference in the distribution of allelic variants of the gene ENPP1 K121Q polymorphism in patients with ACS and the controls.

The value of the given options polymorphism in females was unreliable in patients with ACS and controls (P = 0.280). The distribution of allelic potions K121Q polymorphism in males also did not differ in comparison to patients with ACS and controls (P = 0.320).

Conclusion. There is no link between the polymorphism K121Q of gene ENPP1 and the acute coronary syndrome in males and females.

Key words: ectonucleotide pyrophosphatase/phosphodiesterase, acute coronary syndrome, allelic polymorphism.

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  21. Bertrand ME, Simoons ML, Fox KA, Wallentin LC, Hamm CW, McFadden E, De Feyter PJ, Specchia G, Ruzyllo W. Management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J. 2002;23:1809–1840.
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CONNECTION OF BCL1 POLYMORPHISM OF GLUCOCORTICOIDS RECEPTOR GENE WITH SEVERITY OF COURSE AND OBESITY PATIENTS WITH BRONCHIAL ASTHMA

Authors: Kmyta V.V.

Pages: s45-s51

Abstract


The purpose of our investigation was study the connection between Bcl1 polymorphism of glucocorticoids receptor gene (GR) with severity of course of disease and obesity patients with bronchial asthma (BA).

188 patients with BA and 95 almost healthy patients were examined. Body mass index, the pulmonary function test (PFT)were investigated. Determination of Bcl1 polymorphism of 2d glucocorticoids receptor exongene (GR) performed with FleuryI. etal. method with modifications. Statistically results processing were done with using of the SPSS-17programs.

The results of analyses of the genotype distribution by Bcl1 polymorphism GR gene dependingon severity of BA course showed that C/C genotype associated with easy course of disease, meanwhile, G/G with severe course. The analyzes of distributing allelic variations GR depending onforced expiratory volume in 1 second (FEV1)  showed more expressed obstructive changes in minor allele carries (C/G+G/G) comparing with homozygotes by main allele. We pointed out that patients with BA with C/C genotype index FEV1 showed 68.6 (95% CI 64.9–7.3), and with G/G genotype – 59.9(95% CI 57.02–62.7).

The analysis of genotype distribution by Bcl1 polymorphism GR gene depending on the level FEV1 with consideration BMI showed that genotype C/C mostly occured in patients with normal body mass and FEV1 in normal limits and in range of 60–80% from appropriate values, and genotype G/G –in patients with obesity and severe disorders FEV1.

Obtained results proved the availability of connection between genotypes by Bcl1 polymorphism GR gene, BMI and degree of disorder PFT in patients with BA.

Key words: bronchial asthma, Bcl1 polymorphism, body mass index, the degree of severity.

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References

 

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  14. Pietras T, Panek M, Tworek D,Oszajca K, Wujcik R, Grski P, Kuna P, SzemrajThe BclI single nucleotide polymorphism of the human glucocorticoid receptor gene h-GR/NR3C1 promoter in patients with bronchial asthma: pilot study. Mol Biol Rep. 2011;38(6):3953–3958.

 

 

COMPUTED TOMOGRAPHY CHANGES OF THE BRAIN IN PATIENTS WITH TRAUMATIC BRAIN INJURY AND THEIR DEPENDENCE ON THE -675 4G/5G POLYMORPHISM IN THE PAI-1 GENE

Authors: Potapov O.O., Kmyta O.P.

Pages: s52-s57

Abstract


Secondary changes in the brain that occur during the early posttraumatic period remain a major cause of death in patients with severe traumatic brain injury. The purpose of our study was to analyze brain changes over time in patients with severe traumatic brain injury studying the association between the results of computed tomography examinations and the -675 4G/5G polymorphism in the PAI-1 gene.

We examined 119 patients with severe traumatic brain injury. Computed tomography changes of brain tissues in patients with severe traumatic brain injury were investigated. Determination of the -675 4G/5G polymorphism in the PAI-1 genewas performed. Statistical processing of the results was done with programsSPSS-17.

We found an association between posttraumatic computed tomography changes of brain tissues in patients with severe traumatic brain injury and the genotypes for the -675 4G/5G polymorphism in the PAI-1 gene: namely, more evident and accelerated involution of lesions in patients with 5G/5G genotype; more rapid recovery in patients with 4G/4G genotype; confirmed predisposition to developing secondary complications, pathological lesions evolution in the brain, and secondary ischemic complications in patients with 4G/5G genotype for the investigated polymorphism.

The obtained results proved the availability of connection between genotypes -675 4G/5G polymorphism in the PAI-1 gene, secondary complications, pathological lesions evolution in the brain, and secondary ischemic complications in patients with severe traumatic brain injury.

Key words: traumatic brain injury, computed tomography examination of the brain, the -675 4G/5G polymorphism in the PAI-1 gene.

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LIPID PROFILE AND LEVEL OF INFLAMMATORY MARKERS IN PATIENTS WITH CORONARY HEART DISEASE DEPENDING ON Ɛ4-ALLELE CARRIER Ɛ2/Ɛ3/Ɛ4-GENE POLYMORPHISM OF LIPOPROTEIN E

Authors: Prystupa L.N., Psarova O.V.

Pages: s58-s65

Abstract


Our aim was to investigate the level of blood lipids and inflammatory markers in patients with coronary artery disease (CAD) depending on carrier ɛ4-allele ɛ2/ɛ3/ɛ4-apolipoprotein E gene polymorphism.

Material and Methods. The study involved 150 patients with CAD. Gene polymorphism of apolipoprotein E studied by Hixson et. al. (1990). DNA was extracted from whole blood using the sets DIAtom DNA Prep 100 («Isogene», Russia). rs7412 and rs429358 polymorphisms exon 4 was determined by polymerase chain reaction followed by restriction fragment length analysis. We performed enzymatic colorimetric method using a set of reagents "Olveks diagnosticum" (Russia) in accordance with the manufacturer's methods to study total cholesterol, HDL and TG. We identified CRP, IL-6 and TNF-α to assess the presence of systemic inflammatory response of the body. Their quantitative assessment was performed using the kits JSC "VECTOR-BEST" (Russia) and by enzyme immunoassay technique according to the manufacturer. Processing of the results was performed using the statistical analysis package SPSS 17.0

Results. Analysis of the genetic polymorphism of apoE showed that among 150 patients with CAD carriers ɛ4-allele were 37 (24.7%) patients, whereas no carriers – 113 (75.3%). We established that carriers ɛ4-allele were mostly men 28 (75.7%), while women – 9 (24.3%); statistically significant differences in Pearson χ2 criterion were found (p = 0.566). We found that in patients who are not carriers of allele frequency ɛ4-hypertension, SBP and DBP levels were significantly higher compared with native ɛ4-allele (p = 0.007, 0.058, 0.03, respectively). The analysis of HDL levels in patients with CAD depending on carrier ɛ4-allele showed that patients who are carriers of ɛ4-allele HDL was significantly lower compared with non-carriers ɛ4-allele (p = 0.013). Atherogenic index (AI) was significantly higher in patients who are carriers ɛ4-allele compared with non-carriers ɛ4-allele (p = 0.006). Patients who are carriers ɛ4-allele had higher levels of CRP and IL-6, but statistically significant differences in the Pearson χ2 criterion were found (p = 0.295, 0.492, respectively).

Conclusion. ɛ4-allele carriers have higher levels of blood lipids and inflammatory markers, indicating the progression of atherosclerosis.

Key words: coronary heart disease, apoE gene polymorphism, lipid profile, inflammatory markers.

psaryova@mail.ru

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NEW APPROACHES TO THE DEVELOPMENT OF LIPOSOMAL VIRAL VACCINES

Authors: Davidova T. V., Volianskiy A. Yu.

Pages: 391-404

Abstract

  

Liposomal technology vaccine delivery is currently experiencing a new renaissance. Liposomes (phospholipid vesicles with bilayer) is a versatile and reliable systems of antigens delivery to induce antibodies and T lymphocytes. Over the past 15 years, improved technology liposomal vaccines and today several vaccines containing liposomes with adjuvants approved or have reached the last stage of clinical evaluation. With this in mind, we have provided a systematic review of physical and chemical factors that should be considered designing liposomal vaccines. The overall analysis of the literature clearly shows that these factors (size, charge, composition, method of attachment of the antigen) have significant implications for the potential immunogenicity of the drug and should be carefully chosen. Despite the tendencies of associative connection biophysical parameters vesicles of immunogenicity, the interconnectedness of various biophysical factors determines need to optimize some specific compositions for vaccination programs for each. Although a large number of literary references describes the importance of biophysical parameters of liposomal formulations for the exercise of their specific immunogenicity, many important questions remain unanswered. At the cellular level is not clear how lipid substances affect the processing of the antigen and its presentation? Little is known about the cellular distribution of lipid modified peptides.
Further research is needed to determine mechanistic basis adjuvant action of cationic lipids and liposomal formulations in general. Given the versatility of liposomal carriers and their ability to simultaneous operation of several molecules adjuvants, liposomes seemingly ideal system model to study the phenomenon of synergism in great detail in vitro and in vivo.

Keywords: vaccines, liposomes, immunogenicity.

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SOCIO-ECONOMIC STATUS AND PREVALENCE OF RISK FACTORS CARDIOVASCULAR DISEASE PATIENTS TYPE 2 DIABETES AND HYPERTENSION (LITERATURE REVIEW)

Authors: Bereznyakov I. G., Levadna Y. V., Doroshenko, O. V., Sidorov D. Y , Pozhar V. I.

Pages: 405-416

Abstract

  

The article deals with the socio-economic status (SES) and the prevalence of risk factors (RF) in patients with diabetes mellitus (DM) type 2 and essential hypertension (EH). Determined the prevalence of risk factors, depending on the occupational status, smoking, alcohol consumption, low physical activity influence on mortality according to age. Paying special role metabolic syndrome, its dependence on SES. Attention is given to the link between SES, presence of DM type 2, the presence of hypertension and the prevalence of risk factors for cardiovascular disease. Comorbid diseases becomes actualer when combined diseases have great medical and social importance. These diseases include such common diseases accompanied by high morbidity, disability and mortality, treatment and which prevention causes high economic costs. Diabetes mellitus (DM) type 2 and hypertension can be included for these deasease confidently. Distribution and danger of these diseases give necessity to study the pathogenesis, treatment and prevention.

Diabetes, especially type 2, is a very common disease, and epidemiological studies in recent years suggest the "epidemic of diabetes." primary goal of treatment of patients with hypertension is "to achieve maximum reduction in the long-term total risk of cardiovascular morbidity and mortality. It requires the treatment of all modified risk factors, including smoking, dyslipidemia, abdominal obesity or diabetes, adequate therapy associated with hypertension clinical conditions and reduce high blood pressure. Personal risk factors for cardiovascular disease (smoking, alcohol abuse, sedentary lifestyle, poor diet, obesity) are more common in individuals with low SES. Obesity and smoking are often seen as indicators of social stress. Most studies have reported on the relationship between the parameters of SES and cardiovascular disease. An inverse relationship between SES and metabolic syndrome is established, which is largely mediated by lifestyle.

Кеу words: diabetes mellitus, essential hypertension, socio-economic status, risk factors.

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