CC BY
34
As it can be seen in Table 3, new negative wave T (98.0 %), change of ECG in other (except for Vj-V3) diversions (62.4 %), depression of segment ST (48.9 %), signs of LVH (38.2 %) and «Front» localization of changes in ECG (in diversions Vj-V3) (37.3 %) were revealed most often in ECG ofACS patients at admission. Elevation of segment ST in ECG was established in 14.7 % of patients; new pathological waves Q— in 13.4 % and new complete left bundle branch block — in 0.5 %.
It should be noted that the share of ACS patients with elevations of ST is traditionally higher and forms around 1/3 of ACS patients. Our group had quite a lot of «young» and «light» patients with ACS without elevations of ST, perhaps, this is why they were treated in a common ward and not in an ICU.
Thereupon, data of clinical and biochemical blood tests and other methods of examination in ACS patients at the time of admission were analyzed (Table 4).
Table 4 shows that a mean value of different indicators (biochemical, clinical, echo-cardio graphic etc.) in ACS patients at the time of admission was: creatinine — 89.4 ^mol (min.-max. — 140230 ^mol), glucose — 5.2 mmol/l (min.-max. — 3.3-9.6 mmol/l), glucose in fasting — 4.9 mmol/l (min.-max. — 3.0-8.8 mmol/l), total cholesterol — 6.1 mmol/l (min.-max. — 5.8-6.6 mmol/l), leucocytes — 6.1 thousand/ml (min.-max. — 3.3-5.8 thousand/ml), hemoglobin — 9.8 g/l (min.-max. — 76-120 g/l), hematocrit — 29.6 % (mini.-max. — 27.2-32.7 %), thrombocytes — 42.0 % (min.-max. — 180.0-320.0 thousand/ml) and EF — 42.0 % (min.-max. — 28.0 and 62.0 %).
It should be noted that at the time of admission, 240 ACS patients (39.2 %) had left ventricular ejection fraction < 40 %. Ejection fraction > 40 % was revealed in 372 patients (60.8 %); P < 0.05.
During the analysis according to the values of prognostic scales, it was established that the share of patients with intermediate and high risk of death at hospital according to GRACE scale (> 1 for ACS w/o elevation of ST and > 2 for ACS with elevation of ST) is determined with frequency 53.9 %, and the share with a very high risk of death at hospital according to GRACE scale (> 150 grades) — 9.8 %.
According to RECORD scale, intermediate and high risk of death at hospital (> 2 grades) was noted in 50.6 % of patients, and a very high risk of death at hospital (> 3 grades) — in 13.4 % of patients (P < 0.001).
Conclusions
1. Most common clinical symptoms of ACS are chest pain (93.1 %), heart beating (75.3 %) and fatigue (19.3 %). Most ACS patients have decreased left ventricle ej ection fraction and decreased hemoglobin level and a high risk of death at hospital (50.6 %).
2. Among the deceased from ACS, there were significantly more patients aged > 65. Deceased patients often had MI in their anamnesis (100.0 %) and kidney failure (100.0 %); but they smoked less often, had angina and arterial hypertension. There were significantly more patients of high and very high risk (81.8 %) according to RECORD scale. Those deceased at hospital were given aspirin more often (100.0 %), ACE inhibitors (100,0 %) and AC (100.0 %); thrombolytic therapy and beta blockers were not used (0.0 %).
3. Registers and conduct of registration programs similar to RECORD register helps objectively view the problems ofthe approach to treatment and « saving» prevention of the patients with acute coronary syndrome (ACS) and find solutions for them. In the conditions of the research region, they are acceptable, cost-effective and efficient in optimization of methods of early detection and treatment ofACS.
References:
1. Evstifeeva S. E., Lupanov V. P., Samko A. N. Evaluation of clinical treatment, forecast and efficiency of drug treatment, heart bypass and percutaneous transluminal coronary angiography in patients with ischemic heart disease with constrictive coronary atherosclerosis (data from a 5 year prospective observation)//Cardiology. - 2006. - 6: 4-9.
2. Trostyanetskaya N. A., Bykova E. G., Tretyakova N. S., Boldueva S. A. Risk factors and peculiarities of the course of acute myocardial infarction in women depending on age//Cardio-vascular therapy and prevention. - 2008. - 7(6), Annex 1. - P. 371.
3. Canto J. G., Goldberg R. J., Hand M. M. Symptom presentation of women with acute coronary syndromes: myth vs reality//Arch Intern Med. - 2007, Dec 10. - 167(22): 2405-2413.
4. Asian Pacific Journal of Cancer Prevention. - 2009. - Vol. 10.
5. Boersma E., Pieper K. S., Steyerberg E. W. Predictors of outcome in patients with acute coronary syndromes without persistent ST-segment elevation. Results from an international trial of9461 patients. The PURSUIT Investigators//Circulation. - 2000. - 101: 2557-2567.
6. Erlich A. D., Graytsiansy N. A. et al. Characteristics of patients and treatment before the discharge from hospital//Atherothrombo-sis. - 2009. - № 1(2): 105-119.
Kasymova Gulmira Gafurovna, Scientific Research Institute of Hematology and Blood Transfusion
E-mail: [email protected]
Effect of combined pharmacotherapy lipid peroxidation and activity of enzymes antioxidant protection in rat livergepatoсancerogeneze
Аbstract: When hepatitis carcinogenesis marked imbalance in the system of lipid peroxidation and antioxidant enzyme system. Pharmacotherapy cytostatic leads to even greater intensification of lipid peroxidation. Thus activity of antioxidant defense enzymes even more oppressed. Roncoleukin results to some rebalancing of the system of lipid peroxidation and antioxidant enzyme systems. Which has a temporary nature. The combined use of doxorubicin and ronkolejkin some what reduces the marked of doxorubicin hyperlipidperoxidation and increases the activity of antioxidant enzymes.
Keywords: hepatocarcinogenez, system of lipid peroxidation and antioxidant enzyme systems.
Effect of combined pharmacotherapy lipid peroxidation and activity of enzymes antioxidant protection.
Malignant tumors of the liver, according to the literature, comprise 2-3 % in the structure of cancer [4; 10]. Among all primary liver tumors malignant transformation has to 86-90.2 %, and among all primary Malignant tumors of liver tumors the bulk (about 90 %) of tumors gepat hepatocellular carcinoma of liver [4]. To date, the incidence of the disease is increasing in Uzbekistan (3.8 per 100,000 population), which is probably due to the prevalence of VJ-virus hepatitis B and C, which are the most common cause of hepatocellular carcinoma [9; 13]. One of the mechanisms of neoplastic transformation glue-current is a long-term effect on the body increased the number ofhighly oxidizing [12; 16].
The stages of initiation and promotion of carcinogenesis is dominated by electrophilic compounds that interact directly with the DNA has a direct genotoxic effect and interaction with various chemical compounds — procarcinogens, leads to the formation of carcinogens as a result of hydroxylation, epoxidation and other chemical reactions [15]. However, it should be said that active radicals are one of the highlights of the launch of apoptosis [3; 17]. However, for the induction of apoptosis requires its low physiological concentrations, free radicals, radical formation and causes unwanted excessive radical formation ion up to necrosis or malignant transformation [12].
Despite advances in the treatment of liver cancer mortality remains high mortality. In recent years, to improve the efficiency of the treatment of tumors is apply recombinant interleukin-2 (IL-2) — roncoleukin. It's action is based on the ability to activate cytotoxic potential of NK cells cytotoxic lymphocytes that play a key role in the antitumor surveillance system [2; 7]. However ronkolejkina influence on the processes oflipid peroxidation (LPO) have not been studied at hepatocarcinogen.
Objective
To evaluate the effectiveness of inclusion ronkolejkin correction hyper lipid peroxidation in plasma and liver tissue in DENA — induced carcinogenesis.
Material and methods
The study was conducted on 180 male rats, weight 100-120 g. body/Animals were kept in a vivarium on a standard diet without milk. We used a model DENA-induced hepatocarcinogenesis. DENA synthesis was performed at the Institute of Chemistry of the Academy of Sciences of Uzbekistan laboratory method by V. G. Ev-grafova et al. [6]. The synthesized product contains 98 % DENA, with a specific gravity of 0.943, the boiling temperature 177 °S, a refractive index of 1.438 and a well mixed with water. We used the widespread introduction of the scheme carcinogen DENA, which allows you to get the development of hepatocellular liver cancer [6]. To induce hepatocarcinogen in 170 rats were carcinogen administered intragastric probe 5 times a week at a dose of10 mg/kg body weight for 2 months. The mortality rate at the end of the introduction of the carcinogen was 22.9 %.
After 5 months from commencement of the experiment the survivors 131 rats were divided into 4 groups:
• 1st — 35 rat hepatocarcinogenesis administered saline at a dose of 0.5 ml/100 g.;
• 2nd — 32 rats treated with the antitumor antibiotic dok-sorubicine — 0.6 mg/kg i/p for 3 days (Doxorubicin, "Pharmitalia" firm) [1];
• 3rd — 32 rats treated roncoleukin at 0.006 mg/kg intra-peritoneally (Company "Biotech", St. Petersburg) 3 days;
• 4th — 32 rats received a combination of these drugs in the in tumors inhibits the synthesis of interleukin as in tumors is inhibited by interleukin -2 synthesis.
The drug activates the cytotoxic potential of natural helper and cytotoxic lymphocytes, which play a key role in the antitumor surveillance [2; 7]. The control group consisted of 10 intact rats, kept under the same conditions throughout the experiment. The mortality rate at the end of the experiment was 28.6; 25; 25 and 18.7 %, respectively, groups. Animals were sacrificed at 6,7 and 8 months from the start of the experiment.
The appropriate animal research deadlines sacrificed under light ether anesthesia by decapitation in a cold room with air temperature 0° - +2 °C during killed all ethical norms. In the blood serum malonic dialdehyde (MDA) [1], the enzymes superoxide dismutase (SOD) [1], catalase [8] and the total protein content with micro-biuret method. Statistical processing of the results was performed on Pentium-IV computer using the package at application program.
Results and its discussion
Studies have shown an increase in MDA plasma levels in the 1.19 time at 6 months in hepatocarcinogenesis in rats, and in the future, we observed a sharp decline it and by the end of the experiment was less than 1.72 times (P < 0.05) (Table 1).
Given that, the intensity of lipid peroxidation hyper depends on the activity of the HPA, we studied the activity of SOD and catalase. So, after 6 months we have been revealed to you, sharp inhibition of SOD activity (significant reduction in 2 times). During the progression and metastasis of tumor erythrocyte SOD activity even more inhibited (at 3.77 times, P < 0.001). The activity of catalase in 6 months Dost truly exceeded regulatory parameters in 1.43 times (P < 0.05). During the period of progression, and metastasis of the disease process of catalase activity in blood progress decreased by the end of the experiment, it was 1.29 times (P < 0.05).
Pharmacotherapy hepatitis carcinogenesis Doxorubicin sharply intensified lipid peroxidation processes. MDA level was significantly increased in 1.7; 1.69 and 2.29 times the figures, relatively untreated group to 2.03; 1.73 and 1.33 times — compared to indicators in intact rats, respectively timing at 6, 7 and 8 months. Thus of SOD decreased in 1.16; 1.28 and 1.27 times, the activity of catalase — 1.92; 1.73 and 2.03 times the values of the untreated group. Regarding the values of intact rats was 2.38 for the ODS in; 3.72 and 4.81 times for the catalase — 1.35; 2.29 and 2.63 times, respectively, tively terms 6, 7 and 8 months.
Our findings suggest an important role of reactive oxygen species in the cytotoxic action of anticancer drugs, as the education of free radicals-highly active oxidants is the principal mechanism of most conservative methods of cancer treatment (radiotherapy, chemotherapy and photodynamic therapy) [12]. The antitumor effect of the drug is associated with blocking DENA template activity of DENA polymerase and DENA -dependent RNA polymerase systems, which disrupts the synthesis of nucleic acids.
Action ronkoleukin less evident imbalance in the lipid peroxida-tion and antioxidant enzyme system. If after 6 months, we found no significant differences in the study of the relative values of the untreated animal group, then 7 months MDA level significantly increased, it intensified and adequately AOS enzymes. The same trend continued in the future. It should be noted that the severity of hyper-lipid peroxidation was significantly lower activity of antioxidant enzymes — higher relative to the group values of animals treated with doxorubicin. However, non-spite of these positive developments, of lipid peroxidation and antioxidant enzyme system performance in this group of animals was significantly different from the values of intact rats.
We have obtained positive results were due to the fact that IL-2-domain gives the ability to induce the activity of virtually all clones [2; 7; 14]. Histochemical studies have shown that
cytokines performs a protective role, providing recruitment in the Studies O. E. Cecina et al. (2011), but it was shown that recombi-
pathological focus Add-tional number of effector cells, stimulating nant IL-2 at 0.1 ng/ml has a pro-apoptotic activity against lympho-
their phagocytic activity and hearth launch of antigen-specific re- cytic cells by changing the ratio of anti- (Bcl-2, Bcl-x1) and proapop-
sponse, all of which contributes to the elimination of tumor cells [5]. mitotic (Bad) proteins Bcl-2 family in favor of the latter [17].
Table 1. - The level of MDA, activity of SOD and catalase in blood of rats at gepatocantcerogeneze (M ± m)
Dates and Groups MDA nmol/ml SOD conv/min.mg/ protein Catalase, mol H2O2 min. mg/ protein
6 mon.: intact 3.77 t Q.16 0.212 ± 0.011 0.218 ± 0.015
Group 1 4.SQ t Q.27 а 0.103 ± 0.002 а 0.311 ± 0.021 а
Group 2 7.64 ± Q.37 а' ь 0.089 ± 0.002 а 0.162 ± 0.011 а- b
Group 3 S.Q1 ± Q.26 а 0.111 ± 0.008 а 0.296 ± 0.014 а
Group 4 6.SS ± Q.34 а' ь 0.134 ± 0.012 а' b 0.241 ± 0.017 6
7 mon.: intact 4.12 t Q.32 0.227 ± 0.014 0.224 ± 0.015
Group 1 4.22 t Q.19 0.078 ± 0.001 а 0.170 ± 0.015 а
Group 2 7.13 t Q.2S а' ь 0.061 ± 0.004 а' b 0.098 ± 0.005 а' b
Group 3 S.77 t Q.16 а' ь 0.141 ± 0.011 а' b 0.187 ± 0.009
Group 4 6.SS t Q.24 а' ь 0.128 ± 0.012 а' b 0.153 ± 0.011 а
S mon.: intact 4.34 t Q.14 0.226 ± 0.011 0.239 ± 0.011
Group 1 2.S2 t Q.1S а 0.060 ± 0.001 а 0.185 ± 0.013 а
Group 2 S.7S t Q.22 а' ь 0.047 ± 0.002 а- b 0.091 ± 0.004 а' b
Group 3 3.21 t Q.14 а' ь 0.095 ± 0.004 а' b 0.165 ± 0.009 а
Group 4 S.12 t Q.ll а> ь 0.078 ± 0.003 а' b 0.138 ± 0.007 а- b
Note: a — the difference between the contact and the experimental groups; b — treatment and non- treatment group (P < 0.05).
With the combination of doxorubicin and ronkoleukina MDA level significantly exceeds the value of the untreated group and treated ronkoleukine, but was slightly lower than in the group of rats treated with doxorubicin. The activity of SOD significantly exceeds the value of pre-untreated group and treated with doxorubicin animals, but was slightly lower than in rats treated ronkoleukine. Catalase activity was slightly lower values and untreated groups of animals treated ronkoleukine, but was higher than in the group of rats treated with doxorubicin. In all cases of active-antioxidant enzyme was lower than the values of control rats. Apparently, when co-administered drugs formation of reactive oxygen species in the super-high concentrations of doxorubicin under the action slows down some what, due to activation of antioxidant enzymes, which determines the increase in proapoptotic tumor cell death.
Thus, when unbalance is marked hepatocellular carcinogenesis system lipid peroxidation and antioxidant enzyme system. Therefore, the expediency of different-not only the determination of the activity of antioxidant enzymes and the level of lipid peroxidation products, but also their relationship, which allows, in our view, the differentiated vat stage neoplastic degeneration of the liver. Pharmacotherapy with cytostatic, leads to an even greater intensification of lipid peroxidation system. At the same time the activity of antioxidant enzyme enzyme system protection even more oppressed. Ron-coleukin leads to the restored some balance to recommend measures of lipid peroxidation and antioxidant enzyme system, which has a temporary nature. The combined use of doxorubicin and reduce ronkoleukina several marked doksorubicin giperlipoperoksidat and increases the activity of antioxidant enzymes system.
References:
1.
Андреева Л. И., Кожемякин Л. А., Кушкин А. А. Модификация метода определения перекисей липидов в тесте с тиобарбиту-ровой кислотой//Лабораторное дело. - 1989. - № 1. - С. 41-43.
Бережная Н. М., Горецкий Б. А. Интерлейкин-2 и злокачественные новообразования. - Киев: Наук. думка, 1992. - 172 с. Владимирская Е. Б. Апоптоз и его роль в регуляции клеточного равновесия//Клиническая лабораторная диагностика. - 2002. -№ 11. - С. 25-27.
Готье С. В. Гепатоцеллюлярная карцинома//Российский журнал гастроэнтерологии, гепатологии, колопроктологии. - 1997. -№ 5. - С. 19-21.
Джафарова И. У. Параллели морфологического и иммуногистохимического изучения интерлейкина-2 при злокачественной фиброзной гистиоцитоме мягких тканей//Вестник СПб. мед.академии им. М. М. Мечникова. - 2009. - Т. 30, № 1. - С. 105-109. Евграфов В. Г., Смирнов В. П. О применении нитрозаминов для индукции опухолей//Бюллетень экспериментальной биологии и медицины. - 1966. - Т. 92, № 5. - С. 100-102.
Киселевский М. В. Адоптивная иммунотерапия при злокачественных новообразованиях//Вестник РАМН. - 2003. -№ 1. - С. 40-44.
Коралюк М. А., Иванова Л. И., Майорова И. Г. Определение активности каталазы//Лабораторное дело. - 1988. - № 1. - С. 16-19. Кутлимурадов А. Б. Частота заболеваемости населения Узбекистана злокачественными опухолями: Сб. научн. трудов Уз НИИ онкологии. - Ташкент, 1993. - С. 15-18.
10. Мухин Н. А. Гепатоцеллюлярная карцинома//Врач. - 1997. - № 7. - С. 16-19.
11. Мхитарян В. Г., Бадалян Г. Е. Влияние пероксидированных и непероксидированных ненасыщенных жирных кислот на активность супероксиддисмутазы//Журнал экспериментальной и клинической медицины. - 1978. - № 6. - С. 7-11.
12. Немцова Е. Р., Сергеева Т. В., Безбородова О. А., Якубовская Р. И. Антиоксиданты - место и роль в онкологии//Росс. Онкол. журнал. - 2003. - № 5. - С. 48-53.
Comparison of fixed topical combination glaucoma drugs in patients with open-angle glaucomsa or ocular hypertension
13. Пулатов Д. А. Первичный рак печени: характеристика молекулярно-метаболических аспектов патогенеза и пути повышения эффективности лечения//Дисс. ... д. м. н. - Ташкент, 2005. - 240 с.
14. Симбирцев А. С. Иммунотропные препараты на основе цитокинов. 2006// [Electronic resource]. - Available from: http://www. asvomed.ru/php/content.phpid =697.
15. Турусов В. С., Билицкий Г. А. Канцерогенез. - М., 2000. - С. 106-121.
16. Ткаченко Е. В., Касьян Е. М., Крылова М. Н. Изменения антиокислительного статуса крови крыс в первые дни индуцированного химического канцерогенеза//Российский онкологический журнал. - 1996. - № 2. - С. 29-33.
17. Чечина О. Е., Разанцева Н. В., Новицкий В. В. Белки семейства Bcl-2 - молекулярные мишени проапоптотического действия ИЛ-2 и ИЛ-4//Иммунология. - 2011. - Т. 32, № 3. - С. 127-130.
Bakhritdinova Fazilat Arifovna, Tashkent medical academy, Minister of Health of Republic of Uzbekistan
E-mail: [email protected] Karimov Ulugbek Rasulovich, Syrdarya regional ophthalmologic hospital, Uzbekistan E-mail: [email protected] Mirrakhimova Saida Sh., Tashkent medical academy, Minister of Health of Republic of Uzbekistan
Akshey Khera,
Ophthalmic clinic "Vedanta medical", Tashkent E-mail: [email protected]
Comparison of fixed topical combination glaucoma drugs in patients with open-angle glaucomsa or ocular hypertension
Аbstract: The purpose of study was to compare the intraocular pressure lowering efficacy, safety and cost-efficiency of fixed combinations travoprost 0.004 %/timolol 0.5 % (tim + tarv), brimonidine 0.2 %/timolo0.5 % (tim + brim), brinzol-amide 1 %/timolol 0.5 % (tim + brinz) and pilocarpin 2 %/timolol 0.5 % (tim + pil) in patients with ocular hypertension or open-angle glaucoma. In this prospective, randomized clinical trial included 80 qualifying patients (4 groups) during six month. It was found that the fixed combination travoprost 0.004 %/timolol with 0.5 % is more effective, stabile and safe combination and recommend for long-term therapy of POAG and ocular hypertension. Combination of brimonidine + 0.2 %/timolol 0.5 % and timol + brinsolamid are recommend for fast and effective reduction IOP, short term cost effective therapy of POAG. Combination of pilocarpin 2 % and timolol 0.5 % usually is not recommend for therapy of POAG, but can be use as costly treatment for short time.
Keywords: open angle glaucoma, therapy, fixed combination glaucoma drops.
Bakcgroud
According to the literature to compensate for the intraocular pressure are often (25 to 70 %) is used two or more antihypertensive drug [1; 2; 3]. Today, our market represented a significant arsenal of the fixed combination of antihypertensive drugs, and it is necessary to compare the effectiveness of drugs to determine their characteristics and hypotensive activity. However, the authors of contradictory results [3; 4; 5; 6; 7; 8]. Perhaps this is due to the fact that studies have been conducted in different ethnic groups or different stages of glaucoma, with enough informative methods of research.
According to the requirements of evidence-based medicine, the most reliable are objective imaging technique of the optic nerve — the data of optical coherence tomography (O CT) of the optic nerve (optic disc), and color duplex scanning (CDS) orbit vessels. OCT will identify and quantify the dynamic aspect of the reduction of peripapillary nerve fiber layer (NFL), which is the best indicator of glaucomatous lesions, compared with the computer perimeter [9; 10; 11; 12]. However, the practical application of color duplex scanning orbital vessels, will allow to quantify the condition of blood circulation of the
orbital vessels supplying the optic nerve [13; 14; 15; 16; 17]. According to the literature the most important and reliable parameter of orbital vascular blood flow rate is "resistance index» (Pourcelot's ratio IR) arteria ophthalmica (AO) and posterior short ciliary arteries (PSCA) [18; 19; 20; 21; 22]. resistance index in the AO and PSCA can serve as predictor of progressive deterioration of visual functions in POAG; The authors offer the best of its values: 0.72 and 0.65 for the AO to PSCA [23; 24; 25; 26; 27]. In addition to the above-mentioned indicators are also important indicators of safety, efficiency and ease of use of drugs.
Purpose — to evaluate the features of the hypotensive effect of the fixed combination of timolol 0.5 % + travoprost 0.004 % (tim + trav), timolol 0.5 % brimonidine + 0.2 % (tim + brim), timolol 0.5 % + 1 % brinzolamide (tim + brinz), timolol 0.5 % pilocarpine + 2 % (tim + pil) and their impact on clinical and functional parameters of eye in patients with POAG.
Materials and methods
The survey of 80 patients (158 eyes) with POAG II — III stage. Parameters patient groups are shown in Table 1. The four groups of patients have been formed; The first group (40 eyes) buried
