Method for early identification of risk of developing impaired glucose tolerance in patients with stable effort angina with underlying administering beta-adrenergic blocking agents with no additional vasodilating properties

FIELD: medicine.

SUBSTANCE: invention can be used to identify a high risk of developing impaired glucose tolerance in patients with stable effort angina with underlying administering beta-adrenergic blocking agents with no additional vasodilating properties. Therapy is preceded by conducting 2 exercise tests on the same day to achieve a threshold load power according to the same protocol, initially and 2 hours after administering a single dose of the beta-adrenergic blocking agents. If observing an interval gain of 120 seconds and more from the beginning of the load to the angina attack and/or reduction of an ischemic ST segment on the electrocardiogram not less than 1 mm at the 2nd load as compared to the 1st load, a risk of impaired glucose tolerance is considered to be high. A glucose tolerance test is carried out in these patients 4-5 weeks after the scheduled administration of the beta-adrenergic blocking agents. If impaired glucose tolerance is detected, administering the beta-adrenergic blocking agents is withdrawn. If the 2nd load as compared to the 1st load shows an interval to the angina attack and/or reduction of the ischemic ST segment on the electrocardiogram at a depth not less than 1 mm increasing less than by 120 seconds, a risk of developing impaired glucose tolerance is considered to be negligible. Treatment of these patients with the beta-adrenergic blocking agents is continued without the glucose tolerance test required.

EFFECT: method provides preventing carbohydrate metabolic disorders by the early identification of the high risk of developing impaired glucose tolerance in the given patients by detecting a compensatory increase of the glucose consumption with insulin resistance and a lower availability of free fatty acids to provide myocardial energy needs.

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Nowadays, a large amount of scientific and clinical data on the presence of beta-blockers unwanted systemic metabolic effects, among which the most important are disorders of glucose homeostasis, contributing to the development of prediabetes and diabetes [1, 2]. Considering the fact that among patients with coronary heart disease disorders of carbohydrate metabolism occur approximately in 2 times more often than in the General population [3], the control of carbohydrate metabolism in patients receiving beta-blockers should be timely and adequate.

The problem of prevention of disorders of carbohydrate metabolism when taking beta-blockers is particularly important socio-economic importance in connection with the steady aging of the population, the projected increase in the number of patients with angina taking antianginal drugs, and large expenditures on treatment of patients with diabetes.

The main goal in the appointment of beta-blockers to patients with angina is the achievement of antianginal (ischemia angina attacks) and antiischemic (improving exercise capacity) effects. The basis of therapeutic effect of beta-blockers for angina is the reduction of requirement of a myocardium in oxygen, associated with a slow heart rate juice is asheni (HR), the weakening of the contractility of the heart and lower blood pressure (BP), which reduces the degree of mismatch between the value of coronary blood flow in stenosed coronary arteries and energy demands of the myocardium under load.

In addition, the blockade of beta-adrenergic receptors affects the metabolism of energy substrates during exercise. As a result of inhibition of lipolysis in patients receiving beta-blockers decreases the level of free fatty acids in the blood and is a compensatory enhancement of glucose utilization. In this regard, on the background of beta-adrenergic blockade, the role of glucose to meet the energy deficit that occurs during physical activity [4].

Currently, the most common are beta-blockers without additional vasodilating properties (BB without ice), such as atenolol, metoprolol, talinolol, propranolol, nadolol, tertatolol etc. These drugs are used not only for treatment of angina, but also in other forms of cardiovascular disease: arterial hypertension, chronic heart failure, atrial fibrillation. Welcome BB without ice, as with other beta-blockers, may lead to the development of disorders of carbohydrate metabolism.

In everyday medical practice monitoring, Metabo is the ISM glucose, including in patients receiving beta-blockers, in most cases is limited to determining the level of glycemia on an empty stomach. However, in the first 1-2 months of receiving BB without DIC concentration of fasting blood glucose did not increase and may even decline [5]. As a result of this violation of carbohydrate metabolism caused by the admission of BB without ice, can at the initial stage of treatment to remain unrecognized, the continued administration of the drug in such cases will contribute to their aggravation and, in the future, the development of prediabetes and diabetes.

The most informative method for the detection of disorders of carbohydrate metabolism in patients with ischemic heart disease is the test for glucose tolerance, evaluation of only one indicator of the level of glycemia on an empty stomach is not able to recognize glycometabolism violations of more than 20% of patients [6]. Test glucose tolerance glucose in venous blood to determine 2 times on an empty stomach after an overnight fast 10-11 hours, and 2 hours after ingestion of 75 g glucose dissolved in a glass of warm water. The test results are evaluated in accordance with the criteria of the who 1999: normal glucose levels <110 mg/DL, at a concentration of glucose ≥110 mg/DL and < 126 mg/DL are diagnosed with impaired fasting glucose. 2-hour postprandial glycemia ≥140 mg/DL and <200 mg/DL p is sceneway as impaired glucose tolerance.

A disadvantage and limitation to its widespread use is poor tolerability of this procedure, a considerable part of patients. As a result of this repeated execution test glucose tolerance in the same patient to assess the safety of drug therapy from the point of view of the possible development of disorders of carbohydrate metabolism are rarely, mainly for research purposes [7].

To nivasini methods to identify individuals with a high probability of disorders of carbohydrate metabolism, are the so-called Scor-model to calculate the risk of diabetes of the 2nd type, which include data on anthropometry, dietary habits, peculiarities of the style of life and some others. These models have sufficient validity in the detection of diabetes, but does not allow to assess the risk tolerance to glucose and prediabetes [8].

Also known model for calculating the risk of prediabetes, which takes into account demographic, laboratory parameters (HbA1c, glucose concentration in venous blood on an empty stomach), age, waist circumference, blood pressure and has a high predictive ability in relation to what constitutes a violation of glucose tolerance at the time of the survey [9]. However, this model is not intended for special primeneniyu patients with ischemic heart disease, does not account for its presence in the calculation of the index and, most importantly, it is not possible to estimate the probability of development of disorders of carbohydrate metabolism during treatment, including when taking beta-blockers.

The claimed invention is directed to improving the safety and efficiency of application of the BB without DIC in patients with stable angina and is the creation of a method of early detection of patients with high risk of developing disorders of glucose tolerance in the background of their reception. This allows to adjust therapy, and to reduce the need to test glucose tolerance to oversee the development diabetogenic actions of these drugs.

The technical result of the invention is the prevention of disorders of carbohydrate metabolism due to early detection of high risk violations glucose tolerance in patients with angina admission BB without ice by identifying compensatory increase of glucose utilization in conditions of insulin resistance and reduced availability of free fatty acids for energy needs of the myocardium.

At the same time, this category of patients is the most vulnerable to the negative effects of beta-blockers on the sensitivity of peripheral tissues to insulin, the trail is a journey of which is the development of disorders of glucose tolerance during the first month of receiving BB without ice.

This technical result is achieved by assessing individual antiischemic effect when taking a single dose of BB without ice in a particular patient. The presence of such effect when taking BB without the internal combustion engine is associated with dysfunctions of the insulin/glucose, in particular insulin resistance of peripheral tissues, and reflects the importance of glucose as an energy substrate in the background of the action of beta-blocker.

The method is as follows.

The proposed method is carried out using the method of paired exercise tests, which consists in carrying out the same day, in the morning, no earlier than 2 hours after a light Breakfast, according to the same Protocol 2 tests before reaching the threshold of load power. 1-I load performed prior to receiving a single dose of BB without ice, 2-I - 2 hours after administration. According to the results of each test to determine the magnitude of the time interval from the start of loading until angina medium intensity and/or reduction of ischemic ST segment type depth of ≥1 mm on the electrocardiogram (↓ST≥1 mm). If you increase this time interval of 120 s or more when the 2nd load compared to the 1st - the drug has anti-ischemic effect. When the value of this ratio less than 120 C - antiischemic effect of no is. The method can be applied both in-patient and out-patient, is not difficult for the trained personnel and well tolerated. In addition, it provides additional clinically important information that is associated with drug tolerance, the presence of asymptomatic myocardial ischemia, the effect on hemodynamics, and is recommended for use at the stage of choice of treatment in patients with stable angina who do not have contraindications of exercise tests [10]. Before treatment a patient who is scheduled long-term use BB without ice, conduct a paired exercise test on the treadmill or Bicycle Ergometer with a single dose of the drug. If the data pair exercise test the drug has anti-ischemic effect, the patient has a high risk of developing disorders of glucose tolerance during the first month of his admission. In this case, after 4-5 weeks of use BB without ice conduct a standard test for glucose tolerance, the detection of impaired glucose tolerance drug gradually abolished and prescribe an effective medication to another group.

If the data pair exercise test BB without ice in a single dose does not exert anti-ischemic effect, the patient can take this drug is due to the presence of other indications (for example, about hypertension) without additional test glucose tolerance as risk of developing disorders of glucose tolerance is small.

Examined 43 patients with stable angina. All patients when performing the exercise test occurred angina attack and/or ↓ST≥1 mm.

Before treatment, each patient were conducted paired exercise tests with a single dose BB without ice for the evaluation of anti-ischemic effect (metoprolol 50 mg, atenolol 50 mg, propranolol 40 mg). According to the paired exercise tests the patients were divided into 2 groups: 24 patients, the drug was effective in 19 patients antiischemic effect was absent. Further, all patients received a BB without ice in the initial single dose 2 times a day for 4-5 weeks, at the end of this period conducted control the exercise test 2 hours after administration of the next dose.

To study the effect of BB without ice on carbohydrate metabolism in each patient were performed 2 tests for glucose tolerance: before treatment and after 4-5 weeks of regular use of the drug. In the serum was measured by the glucose concentration automated glucose oxydase method and the concentration of insulin radioimmunoassay method (Insuline IRMA, Immunotech, Czeh Republic). The status of carbohydrate metabolism was evaluated according to who criteria 1999 insulin Sensitivity was determined by the ISI index0,120(Insulin Sensitivity Index), calculated with respect to body weight and levels of glucose and insulin before and 120 min after exercise according to test glucose tolerance [11]. The ISI index0,120reflects mainly the insulin resistance of peripheral tissues. The decrease in ISI0,120indicates reduced sensitivity of tissues to insulin and increase insulin resistance.

According to the paired exercise tests, groups of patients with and without anti-ischemic effect BB without ice did not differ by baseline indicator of physical stress. The duration of the 1st load (without drug) until onset of angina and/or ↓ST≥1 mm was in patients with the presence of anti-ischemic effect 317,3±86,8 with, in patients with no anti-ischemic effect 311,7±90,6 (M±SD, p=0,84). 2 hours after taking the BB without ice the specified index in patients with the presence of anti-ischemic effect increased to 518,6±102,4 (+201,3±69,1 C, p<0,001), while no effect was changed insignificantly and amounted to 363,7±102,7 with (+52,0±35,4, p=0,107). Important was the fact that the pronounced differences in antiischemic efficacy BB without ice was observed however is similar hemodynamic effects of the drug, measured by the dynamics of heart rate and blood pressure, indicating that approximately the same degree of decrease in the demand of oxygen in these groups of patients.

Before treatment groups of patients with and without anti-ischemic effect BB without ice did not differ on levels of glucose and insulin in blood on an empty stomach. However, the test for glucose tolerance were significant differences between these groups of patients in terms of postprandial glucose and insulin. Before treatment, patients with the presence of anti-ischemic effect compared to patients without anti-ischemic effect had higher 2-hour glucose concentration 119,6±21,7 vs 90,6±of 28.0 mg/DL (M±SD, p=0.009) and insulin 68,6±44,5 vs 34,3±37,7 mked/ml (M±SD, p=0.01), indicating that the lack of recovery of the initial level of blood glucose 2 hours after glucose load. Patients with the presence of anti-ischemic effect BB without ice sensitivity of peripheral tissues to insulin, characterized by the ISI index0,120was significantly lower than in patients with no such effect, 74,8±32,5 and USD 114.9±47,0, respectively (p=0.003). In addition, prior to the treatment in 7 of 24 patients with antiischemic effect was identified impaired glucose tolerance, in the group with no antiischemic effect cases narusevicienes to glucose was absent.

After 4-5 weeks of use BB without ice in both groups of patients statistically significant changes in glucose and insulin 2 hours after glucose load compared with the period before treatment, have been identified. However, continued differences between the groups with and without anti-ischemic effect in terms postprandial glucose: 135,3±27,2 vs to 104.8±24.6 mg/DL (p=0.006) and insulin: 64,3±46,2 vs 37,6±27,1 mked/ml (p=0.008).

After 4-5 weeks of use BB without ice among the 24 patients with antiischemic effect of the number of cases of impaired glucose tolerance increased from 7 to 12, and among patients with no anti-ischemic effect of impaired glucose tolerance was not observed.

At the same time, according to control stress test on the treadmill, after 4-5 weeks of treatment in groups of patients with the presence and absence of anti-ischemic effect BB without ice remained level of exercise tolerance achieved with a single dose of the drug. Effect of cumulation or addiction to the drug is not marked. The frequency of angina attacks in patients with the presence of anti-ischemic effect decreased from 7.7±2.2 to 3.7±1.4 in the week (M±SD, p<0,001); in patients without anti-ischemic effect has not changed and amounted to 7.2±2,3 and 6.5±1.4 attacks per week, respectively (M±SD, p=0,23).

The practical is important ski, what in patients receiving BB without DIC concentration of fasting blood glucose in both groups of patients was not increased, which created a false impression about the absence of negative trends in the state of carbohydrate metabolism.

Clinical example 1

Patient L s EA, 58 years. Diagnosis: Ischemic heart disease, angina II functional class (FC). Chronic gastritis.

Were treated with metoprolol. Before treatment:

Paired with physical activity: before taking the drug, the time of occurrence of ↓ST≥1 mm 398, 2 hours after administration of a single dose of metoprolol 50 mg 544 C. Increase the time of occurrence of ↓ST≥1 mm was 146 (>120), a single dose of the drug was provided in the anti-ischemic effect.

HR at rest before taking 50 mg of metoprolol - 80 beats./min, BP 125/75 mm Hg, 2 hours HR 55 beats./min, BP 115/75 mm Hg, the Frequency of angina attacks 8 a week.

Test for glucose tolerance: the concentration of glucose 87 mg/DL, 2 hours after glucose load - 99 mg/DL. Conclusion: the normal fasting glucose and normal glucose tolerance.

After 5 weeks of taking metoprolol 50 mg 2 times a day:

Test for glucose tolerance: fasting glucose 102 mg/DL, 2 hours after glucose load - 167 mg/DL. Conclusion: the normal fasting glucose, impaired glucose tolerance.

HR at rest 58 beats./is in HELL 130/80 mm Hg, the Frequency of angina attacks 3,5 per week.

Thus, in a patient with angina pectoris with normal carbohydrate metabolism before treatment and the presence of anti-ischemic effect in single dose of 50 mg of metoprolol after 5 weeks was identified impaired glucose tolerance, thus remained normal concentration of glucose in blood on an empty stomach. Paired with physical activity helped to correctly predict high risk of developing impaired glucose tolerance. Despite good antianginal effect of treatment with metoprolol was discontinued, appointment of diltiazem.

Clinical example 2

The patient s NS, 57 years. Diagnosis: Ischemic heart disease, angina SFC. Hypertension II Art. Obesity I tbsp. Myopia of an average degree.

Were treated with metoprolol. Before treatment:

Paired with physical activity: before taking the drug, the time of occurrence of ↓ST≥1 mm 344 C, 2 hours after administration of 50 mg of metoprolol 391 C. Increase the time of occurrence of ↓ST≥1 mm was 47 (<120 (C), a single dose of the drug did not antiischemic effect.

HR at rest before taking metoprolol 66 beats./min, a HELL of 145/90 mm Hg, 2 hours HR 59 beats./min, BP 140/80 mm Hg, the Frequency of angina attacks 11 week.

Test for glucose tolerance: glucose concentration Natasha is 99 mg/DL, 2 hours after glucose load - 104 mg/DL. Conclusion: the normal fasting glucose and normal glucose tolerance.

After 4 weeks of taking metoprolol 50 mg 2 times a day:

Test for glucose tolerance: fasting glucose 83 mg/DL, 2 hours after glucose load is 81 mg/DL. Conclusion: the normal fasting glucose and normal glucose tolerance.

HR at rest 63 beats./min, BP 110/70 mm Hg, the Frequency of angina attacks 12,5 per week.

Thus, in a patient with angina pectoris with normal carbohydrate metabolism before treatment and lack antiishemiceski effect at the single dose of metoprolol after 4 weeks of regular use of the drug marked normal fasting glucose and normal glucose tolerance according to test glucose tolerance. Paired with physical activity helped to correctly predict a low probability of violation of glucose tolerance. Angina is not urodeles, however, normalization of blood pressure, and therefore recommended to continue treatment with metoprolol in combination with long-acting nitrates.

Clinical example 3

Patient E s A.S., 59 years old. Diagnosis: Ischemic heart disease, angina PFC. Hypertension II stodulski arthritis of the big toe of the left foot (remission).

Conducted Leche is of the atenolol To treat:

Paired with physical activity: before taking the drug, the time of occurrence of ↓ST≥1 270 mm, 2 hours after administration of 50 mg of atenolol 450 C. Increase the time of occurrence of ↓ST≥1 mm was 180 s (>120), a single dose of the drug showed anti-ischemic effect.

HR at rest before taking 50 mg of atenolol 80 beats./min, BP 115/75 mm Hg, 2 hours HR 55 beats./min, BP 125/75 mm Hg, the Frequency of angina attacks 6 a week.

Test for glucose tolerance: the concentration of glucose 88 mg/DL, 2 hours after glucose load was 98 mg/DL. Conclusion: the normal fasting glucose and normal glucose tolerance.

After 4 weeks of taking atenolol 50 mg 2 times a day:

Test for glucose tolerance: fasting glucose 109 mg/DL, 2 hours after glucose load is 150 mg/DL. Conclusion: the normal fasting glucose, impaired glucose tolerance.

HR at rest 58 beats./min, BP 130/80 mm Hg, the Frequency of angina attacks 4 per week, portability daily loads have improved.

Thus, in a patient with angina pectoris with normal carbohydrate metabolism before treatment and the presence of anti-ischemic effect according to the pairwise exercise test with a single dose of atenolol with the regular administration of the drug was identified impaired glucose tolerance and normal fasting glucose. The results of pregateste the exercise allowed the patient to correctly predict a high probability of violations of glucose tolerance during treatment. Atenolol was cancelled and assigned diltiazem and kardiket.

Clinical example 4

Patient M-s MA, 61, Diagnosis: Ischemic heart disease, angina PFC. Hypertension II senior Supraventricular extrasystole. Status after coronary artery bypass grafting (2001).

Were treated with atenolol. Before treatment:

Paired with physical activity: before taking the drug is the time of occurrence of ↓ST≥1 mm 309 C, 2 hours after administration of 50 mg of atenolol 289 C.

Changing the time of occurrence of ↓ST≥1 mm was -20 C (<120 (C), a single dose of the drug did not antiischemic effect.

HR at rest before taking atenolol 84 beats./min, BP 130/80 mm Hg after 2 hours HR 50 beats./min, BP 105/65 mm Hg, the Frequency of angina attacks 9 a week.

Test for glucose tolerance: fasting glucose 100 mg/DL, 2 hours after glucose load - 69 mg/DL. Conclusion: the normal fasting glucose and normal glucose tolerance.

After 4 weeks of taking atenolol 50 mg 2 times a day:

Test for glucose tolerance: fasting glucose 109 mg/DL, 2 hours after glucose load - 102 mg/DL. Conclusion: the normal fasting glucose and normal glucose tolerance. HR at rest 64 beats./min, BP 120/80 mm Hg, the Frequency of angina attacks 8 a week.

Thus, in a patient with angina pectoris with normal source show the roles of carbohydrate metabolism and the lack of anti-ischemic effect in single dose atenolol amid regular intake of the drug was observed with normal fasting glucose and normal glucose tolerance. Paired with physical activity helped to correctly predict a low probability of violation glucose tolerance when taking atenolol. On the background of treatment, the frequency of angina attacks did not decrease, however, was marked by sustained normalization of blood pressure, arrythmia significantly aradillas. Recommended to continue taking atenolol in previous doses in combination with nitrates.

Clinical example 5

Patient P s VN, 66 years. Diagnosis: Ischemic heart disease, angina PFC. Postinfarction cardiosclerosis (1997).

Were treated with propranolol. Before treatment:

Paired with physical activity: before taking the drug, the time of occurrence of ↓ST≥1 mm 465, 2 hours after administration of 40 mg of propranolol 621 C. Increase the time of occurrence of ↓ST≥1 mm was 156 (>120), a single dose of the drug showed anti-ischemic effect.

HR at rest before taking 40 mg propranolol 73 beats./min, BP 120/80 mm Hg, 2 hours HR 60 beats./min, BP 110/75 mm Hg, the Frequency of angina attacks 8 a week.

Test for glucose tolerance: the concentration of glucose 107 mg/DL, 2 hours after glucose load - 118 mg/DL. Conclusion: the normal fasting glucose and normal glucose tolerance.

After 5 weeks of taking propranolol 40 mg 2 times a day:

Test for glucose tolerance: fasting glucose 09 mg/DL, 2 hours after glucose load - 169 mg/DL. Conclusion: the normal fasting glucose, impaired glucose tolerance.

HR at rest 64 beats./min, BP 125/80 mm Hg, the Frequency of angina attacks 4 per week, the intensity of angina decreased tolerability of daily exercise improved.

Thus, in a patient with angina pectoris with normal carbohydrate metabolism before treatment and the presence of anti-ischemic effect according to the pairwise exercise test with a single dose of propranolol with the regular administration of the drug was identified impaired glucose tolerance and normal fasting glucose. The results of the pairwise test exercise allowed the patient to correctly predict a high probability of violations of glucose tolerance during treatment. Propranolol has been cancelled and assigned verapamil in combination with trinitrolong.

Clinical example 6

The patient Had s G.N., 71, Diagnosis: Ischemic heart disease, angina PFC. Cyst of the liver. A cyst of the right kidney. Chronic prostatitis.

Were treated with propranolol. Before treatment:

Paired with physical activity: before taking the drug is the time of occurrence of ↓ST≥1 mm 456, 2 hours after administration of 40 mg of propranolol - 512 C. Increase the time of occurrence of ↓ST≥1 mm was 56 with (<120 (C), a single dose of p is eparate had no anti-ischemic effect.

HR at rest before taking 40 mg propranolol 86 beats./min, BP 120/70 mm Hg after 2 hours HR 75 beats./min, BP 100/70 mm Hg, the Frequency of angina attacks 6 a week.

Test for glucose tolerance: fasting glucose of 99 mg/DL, 2 hours after glucose load of 75 mg/DL. Conclusion: the normal fasting glucose and normal glucose tolerance.

After 5 weeks of taking propranolol 40 mg 2 times a day:

Test for glucose tolerance: fasting glucose 90 mg/DL, 2 hours after glucose load - 122 mg/DL. Conclusion: the normal fasting glucose and normal glucose tolerance. HR at rest 74 beats./min, BP 115/75 mm Hg, the Frequency of angina attacks 7 a week.

Thus, in a patient with angina pectoris with baseline normal carbohydrate metabolism and the lack of anti-ischemic effect in single dose propranolol on the background of regular intake of the drug was observed with normal fasting glucose and normal glucose tolerance. Paired with physical activity helped to correctly predict a low probability of violation glucose tolerance when taking propranolol. On the background of treatment, the frequency of angina attacks have not diminished. However, the patient had before the treatment the tendency to tachycardia, marked improvement in overall health in connection with the normalization of heart rate, ceased to bother episodes castor the heart with emotional and physical stress. It is recommended to continue taking the drug in combination with nitrosorbid.

Presents clinical examples indicate that the carrying out paired exercise tests with a single dose BB without ice provides an important and reliable information about the likelihood of the development of disorders of carbohydrate metabolism in the background of regular intake of these drugs. This allows you to define a group of patients in need of test glucose tolerance after 4-5 weeks of regular treatment, and allows depending on its results make timely correction therapy.

Patients with angina with "negative" result pair exercise test, at which regular use BB without the internal combustion engine does not provide the desired antianginal effect, have the opportunity to take it due to the presence of other indications - hypertension, heart rhythm disturbance - while having an insignificant risk of developing disorders of carbohydrate metabolism, and do not need to test glucose tolerance to control for possible diabetogenic effect of the drug.

Thus, the found new applications for known methods-paired exercise tests - identification of high risk violations glucose tolerance in patients with angina in the background is the Riem BB without ice, which, of course, will contribute to the prevention of disorders of carbohydrate metabolism associated with the use of the drugs in this group.

For the first time identified a pattern, according to which in patients with stable angina severe clinical efficacy BB without ice, which is characterized by substantial improvement of the portability of everyday stress and ischemia angina attacks associated with risk of developing disorders of glucose tolerance in patients receiving the drug. It is shown that in patients with stable angina, the presence of anti-ischemic effect when taking BB without the internal combustion engine according to a paired exercise test performed before treatment, is associated with reduced sensitivity of peripheral tissues to insulin and may serve as a predictor of early development of impairment of glucose tolerance when taking these drugs.

The presence of such patterns is due to the fact that in patients with angina antiischemic efficacy of BB without ice depends on complex factors related to the influence of the drug on systemic hemodynamics and metabolic processes. Among these factors plays an important role in the possibility of a compensatory increase the use of glucose for energy needs of the myocardium during physical load and ischemia, that depends on the state of glucose homeostasis and its content in the peripheral blood.

Literature

1. Bangalore S, Parkar S, Grossman E, Messerii FH. A meta-analysis of 94,492 patients with beta-blockers determine the risk of new-onset diabetes mellitus. Am J Cardiol 2007; 100:1254-1262.

2. Sarafidis P.A., Bakris G.L. Antihypertensive treatment with beta-blockers and the spectrum ofglycaemic control. Q J Med 2006; 99:431-436.

3. Bartnik M, Ryden L, Ferrari R et al. The prevalence of abnormal glucose regulation in patients with coronary artery disease across Europe. The Euro Heart Survey on Diabetes and the Heart. Eur Heart J 2004, 25, 1880-90.

4. Mora-Rodriguez R, Hodgkinson BJ, Byerley LO et al. Effects of p-adrenergic receptor stimulation and blockade on substrate metabolism during submaximal exercise. Am J Physiol Endocrinol Metab 2001; 280: E752-E760 Showed.

5. Vardeny O, Zebrack J, Gilbert EM. Effects of beta-blocker titration on glucose homeostasis in heart failure. J Pharm Technol 2009; 25(2) : 71-78.

6. Bartnik M, Ryden L, Ohrvik J et al. Oral glucose tolerance test is needed for appropriate classification of glucose regulation in patients with coronary artery disease: a report from the Euro Heart Survey on Diabetes and the Heart. Heart. 2007; 93: 72-77.

7. Hakamaki T, Lehtonen A. Metabolic effects of spirapril and atenolol: results from a randomized, long-term study. Int J Clin Pharmacol Ther 1997 Jun; 35(6) : 227-30.

8. Dong J-j, Lou N-j, Zhao Z-w et al. Evaluation of a risk factor scoring model in screening for undiagnosed diabetes in China's population. J Zhejiang Univ-Sci (Biomed&Biotechnol)2011; 12(10): 846-852.

9. Luders S, Hammersen F, Kulschewski A, et al. Diagnosis of impaired glucose tolerance in hypertensive patients in daily clinical practice. Int J Clin Pract 2005; 59(6):632-8.

10. Kokurina E.V., Kukushkin S. Kaliev, Bochkareva E.V. et al. The choice of effective combined antianginal therapy using a paired exercise tests in patients with stable angina. Methodological rivers is to advise, Moscow, 2003, 19 S.

11. Gutt, M., Davis C.L., Spitzer S.B. et al. Validation of the insulin sensitivity index (ISI(0,120)): comparison with other measures. Diabetes Res Clin Pract. 2000; 47(3):177-184.

The way to identify high risk violations glucose tolerance in patients with stable angina taking beta-blockers without additional vasodilating properties (BB without ice), characterized in that prior to treatment the patient is carried out in the same day 2 exercise test before reaching the threshold power load according to the same Protocol, source and 2 hours after taking a single dose of BB without ice, and in the detection of an increase of 120 seconds or more time interval from the start of loading until angina and/or reduction in the electrocardiogram ST segment ischemic type depth of not less than 1 mm at the 2nd load in comparison with the 1st load the risk of developing disorders of glucose tolerance is considered high, and after 4-5 weeks of regular use BB without the engine being tested on glucose tolerance, the detection of impaired glucose tolerance treatment BB without engine stop, and if in the 2nd load in comparison with the 1st load time interval to onset of angina and/or reduction in the electrocardiogram ST segment ischemic type depth of not less than 1 mm increases less than 120 seconds, ri is to the development of impaired glucose tolerance is considered minor and BB treatment without internal combustion engines spend no dough on glucose tolerance.



 

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1 tbl, 2 ex, 1 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutics and represents a method for identifying a compound applicable for treating periodontal diseases, involving: preparing the first gingival sample from a mammal suffering from an oral disease or condition; preparing the second gingival sample from the mammalian oral cavity; conducting a reaction of the first sample and the analysed compound; conducting a reaction of the second sample and a positive reference that is a compound known as inhibiting an expression of one or more biomarkers specified in a group consisting of DEFB4, CTSS, BGN, BF and IL-12A (halogenated diphenyl ester); measuring a degree of inhibiting the expression of one or more biomarkers by the analysed compound; measuring a degree of inhibiting the expression of one or more biomarkers by the positive reference; and comparing the degree of inhibiting the expression of one or more biomarkers by the analysed compound to the degree of inhibiting the expression of one or more biomarkers by the positive reference; wherein the analysed compound which inhibits the expression of one or more biomarkers equally or more than the above positive reference, is a compound applicable for treating periodontitis.

EFFECT: developing the method for identifying the compound applicable for treating a periodontal disease.

4 cl, 4 ex, 2 tbl, 1 dwg

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to a method for laboratory assessment of the effectiveness in endogenous intoxication treatment in emergency patients consisting in the fact that a patient's venous blood or serum is simultaneously examined for the concentrations of phenyl-acetic, parahydroxyphenyl-acetic, phenyl-lactic and parahydroxyphenyl-lactic acids, and if observing an increased or preserved initially high level of any of the determined acids as compared to their pre-therapeutic level, the therapy is considered to be ineffective.

EFFECT: using the declared method enables simultaneous and objective assessment of the clinical effectiveness of endogenous intoxication treatment in various groups of emergency patients.

4 dwg, 9 tbl, 5 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, and aims at treating chronic obstructive pulmonary disease (COPD). When taking into account a quantity of courses of antibiotic administration for aggravated COPD during previous 12 months, a standard 6-minute walking test involves estimating a 6-minute distance, the heart rate prior to the walking test and oxygen saturation after the walking test; a biomaterial is sampled from the posterior wall of the pharynx by oropharyngeal smears to recover DNA and to sequence; observing proteobacteria involves recoding of the derived data into a qualitative variable; genome DNA is recovered from the COPD patients' blood that is followed by genetic typing by CD14 rs2569190 and IL18 rs1946518 genes; the genetic typing data are pre-recorded into digital values to calculate a discriminant function and to make a forecast.

EFFECT: presented method enables a higher accuracy, information value and sensitivity and enables predicting a severity of COPD effectively, as well as differentiating a severe and very severe clinical course of a moderate and mild COPD.

1 dwg, 4 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: group of inventions relates to a system and a method of control of at least one blood parameter of a particular patient with application of an access device for creation of access to the patient's blood through skin, a device of sampling for blood sampling for obtaining the blood sample, a device of blood test, a calculation device for calculation of medicinal parameters of medication, which must be introduced to the patient, and a supplying device for supply of medication with the calculated medicinal parameters. Identification of blood samples is realised with application of barcodes.

EFFECT: achievement of a higher accuracy and reliability of control.

11 cl, 3 dwg

FIELD: medicine.

SUBSTANCE: invention refers to a method for prediction of increasing a cardio-malleolar-vascular stiffness index in the patients with chronic obstructive pulmonary disease combined with ischemic heart disease which involves studying initial systemic inflammatory biomarkers of C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-alpha) and anti-inflammatory interleukine 4 (IL-4) and calculating the discriminant equation D=1.42*(TNF-α)+0.78*(CRP)-0.534*(IL-4), and if D is more than 4.82, a one-year increase of the cardio-malleolar-vascular stiffness index for one year is predicted, and if D is 4.82 or less, no increase of the cardio-malleolar-vascular stiffness index is predicted.

EFFECT: more effective prediction of increasing the cardio-malleolar-vascular stiffness index.

2 ex

FIELD: biotechnology.

SUBSTANCE: invention is a method of determining in an athlete of state of fatigue and a state of "overtraining" on increased gene expression of tryptophanyl-total RNA synthetase (TRSase). The method comprises taking a control sample from the athlete prior to intense training and the test sample after an intense training. As the sample the sample of blood or scraping or flushing with the oral cavity is used. The obtained cells are selected and washed. Total RNA is isolated from the cells. Reverse transcription is carried out and then amplifying of the cDNA obtained. The gene expression in TRSase is assessed in test and the control samples. Fatigue state and the state of "overtraining" is determined in case of a significant increase in gene expression level of TRSase in the test sample compared with a control sample, namely more than 1.45 times.

EFFECT: invention enables to increase significantly informational content, to simplify and accelerate the procedure of testing.

4 cl, 1 tbl, 3 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to medicine, specifically cardiology, and concerns treating chronic cardiac failure. That is ensured by administering a pharmaceutical composition containing an activated potentiated form of very-low-dose angiotensin II receptor antibodies and an activated potentiated form of very-low-dose endothelial NO-synthase antibodies.

EFFECT: method provides improving quality of life and higher tolerance to physical loads in the given group of patients.

11 cl, 2 ex, 2 tbl

FIELD: medicine.

SUBSTANCE: invention can be used for preventing developing cognitive disorders in patients suffering from ischemic heart disease (IHD) after complete coronary bypass surgery. For this purpose, 10-14 days before the planned surgery with underlying standard drug therapy containing ACE inhibitors, beta-blockers, nitrates, calcium antagonists and acetylsalicylic acid, rosuvastatin is additionally prescribed in a daily dose of 20 mg nocte. After the coronary bypass surgery, taking the preparation is continued for the whole hospital period, taking continuously after discharge from the hospital is recommended.

EFFECT: method enables preventing developing early postoperative cognitive dysfunction in the patients following the cardiosurgical complete bypass procedures.

5 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: 10 daily procedures of ozone therapy are performed. The 1st and 2nd procedures involve saturating 0.9% sodium chloride 200 ml with ozone-oxygen gas mixture in the concentration of 10 mg/l for 2 minutes and administering intravenously for 20 minutes. For the 3rd and 4th procedures, 0.9% sodium chloride 200 ml is saturated with ozone-oxygen gas mixture in the concentration of 15 mg/l for 2 minutes and administered intravenously for 20 minutes. According to the 5th, 6th, 7th, 8th, 9th and 10th procedures, 0.9% sodium chloride 200 ml is saturated with ozone-oxygen gas mixture in the concentration of 20 mg/l for 2 minutes and administered intravenously for 20 minutes. Ozone therapy is further followed 1 hour later with 10 sessions of gravity therapy, which involves the four-staged exposure of a patient to centrifugal forces in the direction from head to lower extremities. At the first stage, a centrifuge rotation speed is 32 rpm with a length of the session being 10 min - 1 session. At the second stage, the centrifuge rotation speed is 34 rpm with a length of the session being 10 min - 2 sessions. At the third stage, the centrifuge rotation speed is 36 rpm with a length of the session being 15 min - 3 sessions. At the fourth stage, the centrifuge rotation speed is 36 rpm with a length of the session being 20 min - 4 sessions.

EFFECT: invention enables achieving collateral blood flow stimulation, atherosclerosis regression, a lower degree of ischemia in patients with obliterating lower extremity atherosclerotic vascular disease by a combination of methods of gravity and ozone therapies.

1 ex

FIELD: biotechnology.

SUBSTANCE: invention relates to binuclear form of dinitrosyl iron complex with ethyl ether of glutathione (DNIC-EEG) of the formula [(EEGS)2Fe2(NO)4] with the structural formula: , where R-S represents ethyl ether of glutathione containing a thiol group. The invention also relates to a composition for reducing functional disorders of myocardium subjected to hypoxia-reoxygenation which contains binuclear form of dinitrosyl iron complex with ethyl ether of glutathione (DNIC EEG) as defined above and a pharmaceutically acceptable carrier. Also the use of DNIC-EEG is disclosed as antihypoxic agent.

EFFECT: reduction of hypoxic contracture, arrhythmias intensity and improvement of recovery of contractile function of the heart after reoxygenation.

3 cl, 1 tbl, 16 dwg, 4 ex

FIELD: biotechnology.

SUBSTANCE: invention relates to an agent for treatment of ischemic lesions of tissues, which is a mixture with the ratio of 1.5-3 of two cultures of mesenchymal stem cells, one of which is modified by the genetic structure based on the viral vector which provides hyperproduction of vascular endothelial growth factor, and the other is modified by the genetic structure based on the viral vector which provides hyperproduction of angiopoietin, and a method of treatment of ischemic lesions of tissues by puncture of ischemic tissue, and can be used in medicine.

EFFECT: invention enables to achieve effective vascularisation and repair of ischemic tissue.

4 cl, 4 dwg, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new phenylpyrimidone derivatives of formula I possessing the properties of a phosphodiesterase type 5 (PDE5) inhibitor. The compounds of formula I can be used for treating various vascular disorders, such as erectile dysfunction, pulmonary arterial hypertension, etc. In formula each R1 and R2 independently means H; C1-C10alkyl; halogen; CF3; CN; OR5; NR6R7; NHCOR8; aryl; or C1-C4alkyl optionally substituted by OR5; Z means OR3; R3 means C1-C6alkyl or C1-C3alkyl, substituted by C1-C3alkoxy group; R4 means SO2NR6R7; NR9R10, providing NR9R10 is other than NH2; COR11; OR12; or R4 means 5-6-merous heterocyclyl optionally substituted by one or more substitutes specified in a group consisting of OH and C1-C6 alkyl; or R4 means 5- or 6-merous cyclic monosaccharide group; R5 means C1-C6alkyl; C1-C4alkyl optionally substituted by C1-C4alkoxy group; each R6 and R7 independently means H, OH, C1-C6alkyl, C1-C6alkoxy group, C3-C6alkenyl, C3-C6cycloalkyl, adamantyl, C3-C8lactamyl, aryl, Het or (CH2CH2O)jH, wherein j is 1-3; or each R6 and R7 independently means C1-C6alkyl, optionally substituted by OH, C1-C4alkoxy group, SO3H, SO2NR13R14, SO2R16, NR13R14, aryl, Het or 5-6-merous heterocyclyl; or each R6 and R7 independently means 5-6-merous heterocyclyl optionally substituted by one or more substitutes specified in a group consisting of C1-C6 alkyl and C1-C6alkyl substituted by hydroxyl; or R6 and R7 together with a nitrogen atom attached whereto form 5-7-merous heterocyclyl optionally substituted by one or more substitutes specified in a group consisting of OH, COOR8, (CH2CH2O)jH, wherein j is 1-3, C1-C4alkoxy group, Het and C1-C6alkyl substituted by aryl; or R6 and R7 together with a nitrogen atom attached whereto form a glucosyl amino group, an amino acid residue, a residue of an amino acid ester or an amino amide residue. The other radical values are specified in the patent claim.

EFFECT: invention refers to pharmaceutical compositions based on the above compounds, using them, methods for preparing the compounds, and intermediate products.

18 cl, 2 tbl, 224 ex

FIELD: medicine.

SUBSTANCE: preparation citicoline is administered for the purpose of preventing cerebral ischemia in precerebral vasculoplasty prior to and after a carotid occlusion. Prior to the occlusion, citicoline is administered in a dose of 2000 mg in 0.9% sodium chloride 400 ml for a period of time sufficient for approaching the operated vessels, and terminated 5-7 minutes prior to the occlusion. After the occlusion, citicoline is administered starting from the second postoperative day for 5-8 days daily once a day, in a dose of 1000 mg in 0.9% sodium chloride 200 ml.

EFFECT: more effective prevention of cerebral ischemia in precerebral vasculoplasty by the empirically selected regimen of the staged administration of citicoline.

4 ex

FIELD: veterinary medicine.

SUBSTANCE: for correction of skeletal muscle ischemia in rats with ischemia of lower leg muscles, modelled on the second day of the experiment, resveratrol is intragastrically administered in a daily dose of 2.0 mg/kg every 46 hours of the first 7 days of the experiment. The microcirculation level in the muscle of lower leg was evaluated on the 28th day of induction of ischemia.

EFFECT: effective treatment of skeletal muscle ischemia in the experiment due to stimulation of neoangiogenesis.

1 ex, 1 tbl

FIELD: medicine.

SUBSTANCE: invention describes using S-amlodipine nicotinate in treating cerebrovascular disorders specified in a group: haemorrhagic stroke, ischemic stroke, including transient global ischemia. A pharmaceutical composition for treating the cerebrovascular disorders contains S-amlodipine nicotinate as an active ingredient in an effective amount of 0.1 mg to 50 mg per a dose, and pharmaceutically acceptable excipients. The composition represents either a tablet, or a solution for injections.

EFFECT: expanding the usage of S-amlodipine nicotinate.

2 cl, 3 dwg, 3 ex

FIELD: medicine.

SUBSTANCE: invention refers to biotechnology, more specifically to using microRNA (miRNA) for treating pathological cardiac hypertrophy, myocardial infarction or cardiac failure. The method provides introducing a first anti-sense oligonucleotide containing a sequence that is at least partially complementary to the mature nucleotide sequence miR-208a or miR-208b, and a second anti-sense oligonucleotide containing a sequence that is at least partially complementary to the mature nucleotide sequence miR-499 into an individual suffering the cardiac activity.

EFFECT: combined introduction of the above oligonucleotides ensured by manifesting the synergetic effect enables a more effective decrease of the expression or activity of miR-208a or miR-208b and miR-499 in individual's cardiac cells.

30 cl, 7 dwg, 5 ex

FIELD: medicine.

SUBSTANCE: method involves intravenous allogeneic transplantation of multipotent mesenchymal stromal cells recovered from the placenta in an amount of 6 mln cells/kg. Additionally, haemopoietic stem cells recovered from umbilical blood in an amount of 300 thousand cells/kg are introduced.

EFFECT: method enables reducing the number of cytogenetically changed cells, promotes activating myeloid tissue regeneration in old laboratory animals.

4 tbl, 1 ex

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