[The methods for the protection against counterfeit medications. Part 1. The estimation of the quality of metoprolol succinate substance and tablets from different manufacturers in terms of "identity" and "active ingredient content"].

This paper was designed to report the results of analysis of metoprolol succinate substance and tablets obtained from two manufacturers, Akrikhin (Russia) and AstraZeneca (Sweden). The analysis was performed by spectroscopy in the near IR region and followed by the chemometric treatment of the data obtained. The method was used to confirm the "identity" of metoprolol succinate tablets. The approach to distinguishing the differences between pharmaceutical dosage forms produced by different manufacturers is proposed. Also, the method for the qualitative determination of metoprolol succinate in the pharmaceutical formulations has been developed.

[Methods for the protection against counterfeit medications. Part 2. The assessment of interlot dispersion of the metoprolol succinate tablets fabricated by different manufacturers].

This paper reports the results of analysis of the metoprolol succinate tablets fabricated by two different manufacturers, Akrikhin (Russia) and AstraZeneka (Sweden) by near-IR spectroscopy in the combination with the chemometric processing of the data obtained (discriminative analysis). It is concluded that this method is applicable for the assessment of interlot dispersion of the metoprolol succinate tablets.

Trimetazidine in Angina Combination Therapy--the TACT study: trimetazidine versus conventional treatment in patients with stable angina pectoris in a randomized, placebo-controlled, multicenter study.

The aim of this study was to assess the efficacy and acceptability of trimetazidine (TMZ) in combination with hemodynamic agents (beta-blockers or long-acting nitrates) in 177 stable angina patients. In this randomized, placebo-controlled study (TACT: Trimetazidine in Angina Combination Therapy), stable angina patients resistant to nitrates or beta-blockers were selected. After a 1-week selection period (W0), patients who had a difference of <10% in duration between 2 positive exercise tests, defined as 1-mm ST-segment depression (STD) 80 milliseconds after J point with angina pain or 1.5 mm without pain were randomly treated with TMZ (20 mg t.i.d., n = 90) or placebo (Pbo t.i.d., n = 87) orally. A final exercise test was performed after 12 weeks of treatment (W12). The efficacy was assessed by exercise test duration, time to 1-mm STD, time to angina onset, mean number of angina attacks, mean short-acting nitrate consumption, and rate-pressure product. Differences (W12 - W0) in these parameters were analyzed using the Student t test. All statistical tests were conducted at the 5% significance level. At inclusion and during the study, 52% of patients received long-acting nitrates, and 48% were treated with a beta-blocker as monotherapy. At the beginning of the study, the TMZ and Pbo groups were statistically homogeneous with respect to all analyzed characteristics (demographic characteristics, characteristics of anamnesis, characteristics used for evaluation of antianginal therapy efficacy). For various reasons, 11 patients (7 from the Pbo group and 4 from the TMZ group) were excluded from the trial. A total of 166 patients (80 from the Pbo group and 86 from the TMZ group) completed the study in full compliance with the protocol. After 12 weeks of therapy, exercise test duration increased from 417.7 +/- 14.2 (W0) to 506.8 +/- 17.7 seconds (W12) in the TMZ group versus 435.3 +/- 14.8 (W0) to 458.9 +/- 16.2 seconds (W12) in the Pbo group (P < 0.05). Time to 1-mm STD increased from 389.0 +/- 15.3 (W0) to 479.6 +/- 18.6 seconds (W12) in the TMZ group versus 411.8 +/- 15.2 (W0) to 428.5 +/- 17.3 seconds (W12) in the Pbo group (P < 0.05). Time to onset of anginal pain increased from 417.0 +/- 16.9 (W0) to 517.3 +/- 21.0 seconds (W12) in the TMZ group versus 415.1 +/- 16.5 (W0) to 436.4 +/- 18.5 seconds (W12) in the Pbo group (P < 0.005). The mean number of anginal attacks per week decreased from 5.6 +/- 0.6 to 2.7 +/- 0.5 in the TMZ group versus 6.8 +/- 0.7 to 5.1 +/- 0.7 in the Pbo group (P < 0.05), mean consumption short-acting nitrates per week decreased from 5.2 +/- 0.9 to 2.8 +/- 0.8 in the TMZ group versus 5.5 +/- 0.8 to 4.1 +/- 0.9 in the Pbo group (NS). No change in the rate-pressure product was seen in both. The combination of trimetazidine with beta-blockers or long-acting nitrates significantly improves exercise stress test parameters and angina symptoms compared with placebo. Due to its metabolic effect, free of any hemodynamic action, trimetazidine has proven to be beneficial for combination in patients with stable angina.

[Trimetazidine in pectoris patients older than 65 years with stable angina]. / Trimetazidin pri stabil'noi stenokardii napriazheniia u bol'nykh starshe 65 let.

AIM: To study efficacy of trimetazidine including action on quality of life in patients over 65 years of age with stable angina pectoris. MATERIAL: Seventy two patients (75% men, age 65-80 years) with stable class II-III angina not completely controlled by baseline conventional combined antianginal therapy (nitrates, beta-blockers, and calcium antagonists). METHODS: Trimetazidine (60 mg/day) was added to baseline therapy for 12 weeks. Clinical evaluation before and after trimetazidine included registration of symptoms, analysis of parameters of treadmill exercise tests (Bruce protocol) including characteristics of post test recovery and assessment of quality of life (Seattle Angina Questionnaire). RESULTS: Sixty nine patients concluded the protocol. The use of trimetazidine was associated with significant (p<0.0001) improvement of quality of life, significant prolongation of exercise time before 1 mm ST depression (p<0.0005), exercise time before appearance of angina (p<0.0001), time before angina cessation after end of exercise (p<0.01), significant reduction of number of anginal attacks (p<0.01), and diminishment of consumption of short acting nitrates (p<0.01). CONCLUSION: Addition of trimetazidine to conventional antianginal therapy in elderly patients was associated with improved quality of life, increased exercise tolerance and decreased clinical signs of stable angina.

[Antihypertensive efficacy, tolerance and safety of lisinopril (sinopril) and captopril (capoten) in patients with mild and moderate arterial hypertension]. / Antigipertenzivnaia éffektivnost', perenosimost' i bezopasnost' lizinoprila (sinoprida) i kaptoprila (kapotena) u bol'nykh miagkoi i umerennoi arterial'noi gipertoniei.

AIM: To compare effectiveness, tolerance and safety of two inhibitors of angiotensin-converting enzyme--sinopril (lisinopril) and capoten (captopril)--in outpatient treatment of patients with mild and moderate hypertension. MATERIALS AND METHODS: The patients were randomly assigned to sinopril or capoten groups. Sinopril was given in daily dose 10-40 mg, capoten--in daily dose 25-100 mg for 8 weeks. In insufficient antihypertensive effect of monotherapy on day 21, hydrochlortiaside was added. The effect was judged by influence on arterial pressure, heart rate, tolerance (questionnaire), safety (blood count, urinalysis. ECG). RESULTS: Sinopril produced good antihypertensive effect in 73.3% of patients (monotherapy) and 88.9% (combined therapy). For capoten it was 68.9 and 82.2%, respectively. The time of the beginning of the antihypertensive effect (4-20 days after the start of the treatment) for sinopril and copoten differed insignificantly and depended on hypertension severity (mild or moderate). Tolerance of both drugs was good, serious side effects were absent. Discontinuation of the drugs was needed in 4% of patients, only. No negative action on bioelectric activity of the heart, clinical and biochemical blood indices were found. CONCLUSION: Sinopril and capoten demonstrate high antihypertensive activity.

[Experimental validation of the use of betamecil in ophthalmology]. / Eksperiemntal'noe obosnovanie primeneniia betametsila v oftal'mologii.

Wound-healing activity of 2% betamicil ointment in comparison with the traditional stimulants of corneal repair regeneration (methyluracyl and solcoseril) was studied in experiments. The rate of epithelialization of a standard trephination wound in rabbit cornea (28 animals), mitotic activity of the anterior corneal epithelium, and strength of the regenerated tissue were assessed after use of different stimulants and in control. A maximal positive effect of local betamicil (2% ointment) was observed: the wounds epithelialized 57% sooner than in control, but there was no reliable difference from solcoseril; the regenerate of linear corneal wound was 1.5 times stronger. Use of this ointment in ophthalmology is validated.

[Role of Helicobacter pylori in the etiology of duodenal ulcer recurrence after selective proximal vagotomy]. / Rol' Helicobacter pylori v vozniknovenii retsidivov iazvennoi bolezni dvenadtsatiperstnoi kishki posle selektivnoi proksimal'noi vagotomii.

126 patients with duodenal peptic ulcer were examined before and in different periods after operation for selective proximal vagotomy (SPV). Endoscopy was performed and Helicobacter pylori (HP) was detected by the urease, bacteriological, and histological methods. The urease test proved to be the most informative, simple, and available method for revealing infection of the gastric mucosa by HP. The frequency of HP detection by this method made up 97-98%. The frequency of ulcer recurrences after SPV coincided with the degree of contamination of the mucosa with HP and increased to 15% in high contamination. Treatment with agent eliminating HP in the early period after SPV promoted cicatrization of the ulcer.

[Leocaine--a new generation of local anesthetics]. / Leokain--mestnyi anestetik novogo pokoleniia.

Leocaine is a new crystal beta-modification of beta-dimethylaminoethyl ether of n-butylaminobenzoic acid hydrochloride. Its chemical formula is the same as for dicaine, but it has a number of advantages over this drug. The anesthetic activity of leocaine is 2.5 times higher than that of dicaine. By the duration and depth of anesthesia 0.3% leocaine solution corresponds to 1% dicaine. Leocaine exerts no toxic effect on the corneal epithelium and its instillation into the conjunctival cavity does not result in the reactive dilatation of corneal or episcleral vessels. Leocaine solution is stable for 2 years. Clinical trials of leocaine carried out on more than 2500 patients showed virtually complete absence of side effects. Commercial manufacture of leocaine is launched at present. One of the commercial preparations represents a 0.3% solution of the active substance in isotonic NaCl solution. Another drug contains, besides leocaine, methylcellulose. Eye drops with leocaine are recommended for practical ophthalmology instead of dicaine for local anesthesia. The drugs are permitted for medical use and commercial manufacture by the Ministry of Health and Medical Industry of Russia.

[The preoperative assessment of concomitant ischemic heart disease in patients with an abdominal aortic aneurysm]. / Predoperatsionnaia otsenka soputstvuiushchei ishemicheskoi bolezni serdtsa u bol'nykh s anevrizmoi briushnoi aorty.

To reveal and evaluate the severity of concurrent coronary heart disease (CHD) in patients with atherosclerotic aneurysm of the abdominal aorta and to optimize preoperative preparation and intraoperative management, 38 patients underwent comprehensive physical examination, echocardiography, a set of ECG exercise tests. Concurrent CHD was encountered in 87% of cases with abdominal aortic aneurysm. The specific feature of CHD in this aortic abnormality is the predominance of its severe forms as evidenced by findings of coronary circulatory reserve. The incidence of postoperative events is directly related to the reserve of coronary circulation. With all these facts, patients with atherosclerotic aneurysm of the aorta should undergo ECG exercise tests and, depending on the findings, differential antianginal therapy in the preoperative period and nitrate use under the control of central hemodynamics during surgery.

[Functional state of the myocardium during transesophageal cardiac pacing in patients with ischemic heart disease selected for surgical treatment based on nuclear stethoscope findings]. / Funktsional'noe sostoianie miokarda v usloviiakh chrespishchevodnoi élektrokardiostimuliatsii u bol'nykh ishemicheskoi bolezn'iu serdtsa na étape otbora k khirurgicheskomu lecheniiu po dannym iadernogo stetoskopa.

A nuclear stethoscope was used to examine central hemodynamic parameters and myocardial contractility in 70 patients with coronary heart disease (CHD). The findings were analyzed according to the degree of cicatricial changes in the myocardium and coronary atherosclerotic lesion. The patients, unlike apparently healthy individuals, were found to show an increase in systolic cardiac output and a decrease in left ventricular ejection fraction in response to transesophageal cardiac pacing. As the cicatricial changes in the myocardium became profound, the maximum left ventricular performance decreased mainly due to the myocardial factor, while there was a reduction in the chronotropic reserve along with relatively slight signs of myocardial dysfunction when coronary atherosclerotic lesion progressed.

[Detection of cardiac insufficiency by computer-assisted monitoring of the response of intra-cardiac hemodynamics to exercise test in patients with ischemic heart disease with similar lesions of the coronary arteries (patient selection for the aortocoronary bypass)]. / Vyiavlenie serdechnoi nedostatochnosti s pomoshch'iu monitorno-kom'iuternogo analiza vnutriserdechnoi gemodinamiki na nagruzochnyi u bol'nykh ishemicheskoi bolezn'iu serdtsa z odinakovym porazheniem koronarnykh arterii (na étape otbora k operatsii aortokoronarnogo shuntirovaniia).

Preoperative identification of cardiac insufficiency in patients with ischemic heart disease (IHD) has proved essential for the success of surgery on the coronary arteries. To provide for an objective assessment of the contractile function of the myocardium in selecting candidates for surgery among IHD patients with over 70-percent narrowing of one, two, and three coronary arteries, use was made of the central hemodynamics indices in response to the loading test during right heart catheterization with computer-assisted monitoring and mathematical analysis. Two patient groups were distinguished during the hemodynamic loading test: group I showing a high and effective chronotropic reserve (+X) and group II presenting a negative chronotropic reserve (-X). It was established that with equal numbers of narrowed coronary arteries and similar clinical manifestations, the estimates of myocardial contraction may differ which determines indications for surgery and preoperative care.

[Indications for aortocoronary shunting in relation to ejection fraction and segmental activity of the left ventricle (data of the coronarography, ventriculography and intra-cardiac hemodynamics)]. / Pokazaniia k operatsii aortokoronarnogo shuntirovaniia v zavisimosti ot fraktsii vybrosa i segmentarnoi aktivnosti levogo zheludochka (po dannym koronaroventrikulografii i vnutriserdechnoi gemodinamiki).

The left-ventricular ejection fraction, reflecting the contractile capacity of the myocardium according to the clinical data, is the most objective criterion in indication for the operation for aortocoronary shunting. The indices of central hemodynamics appearing in response to the exercise test during intracardiac catheterization of the right heart and monitor-computer control with mathematical analysis were used in objective appraisal of the left-ventricular ejection fraction in selecting for surgical treatment patients suffering from ischemic heart disease with normal and reduced ejection fraction of the left ventricle. Two gradations of patients with ischemic heart disease were set apart during the hemodynamic exercise test: the first--patients with a high and effective chronotropic reserve--subgroup I("+X") and the second--patients with a poor and ineffective chronotropic reserve--subgroup II("--X"). It was found that in a single-valued left-ventricular ejection fraction (normal or low) in patients with ischemic heart disease there may be the presence or absence of latent cardiac insufficiency according to the results of the hemodynamic exercise test which must be determined in indications for surgical treatment.

[Radionuclide ventriculography in the evaluation of left-ventricular function in patients with arterial hypertension]. / Radionuklidnaia ventrikulografiia v otsenke funktsii levogo zheludochka u bol'nykh arterial'noi gipertenziei.

Systemic and intracardiac hemodynamic parameters were examined in 29 patients with arterial hypertension by radionuclide ventriculography. No impairments were found in resting left ventricular pump function in the patients. Left ventricular diastolic function exhibited 24 and 34.5% reductions in left ventricular filling rate and its peak filling rate, respectively, as well as a 44.8% increase in peak filling rate time. To assess the potentialities of myocardial adaptation to a postoperative decrease in blood pressure, artificial hypotension test by using the antihypertensive agent naniprus was performed in 15 patients. This test identified a group of patients with pronounced left ventricular diastolic dysfunctions who required a goal-oriented preoperative preparation. It also defined the principles of this preparation.

[Thyroid hormone content of the blood plasma and tolerance for physical loading in ischemic heart disease patients]. / Soderzhanie tireoidnykh gormonov v plazme krovi i tolerantnost' k fizicheskoi nagruzke u bol'nykh ishemicheskoi bolezn'iu serdtsa.

Blood thyroid hormones were measured before and after the rationed exercise test in 79 patients with angiographically verified diagnosis of coronary heart disease. A relationship was demonstrated between postexercise blood T3 variation and functional coronary circulation reserve. Hormonal baselines, and exercise-induced blood T4 changes were basically similar in patients with coronary disease of different severity. The results are suggestive of pathogenetic importance of thyroid function in these patients.

[The scissors phenomenon in the reaction of hormonal systems to the physical load test in ischemic heart disease patients]. / "Fenomen nozhnits" pri reaktsii nekotorykh gormonal'nykh sistem na probu s fizicheskoi nagruzkoi u bol'nykh ishemicheskoi bolezn'iu serdtsa.

A difference between baseline and final plasma hormonal (insulin, cortisol, somatotrophic hormone, triiodothyronine (T3) and thyronine (T4) levels, related to the pattern of response to physical stress, was demonstrated in 67 coronary patients with angiographically verified diagnosis. Post-exercise increase in these hormones was associated with their lowered baseline and elevated final blood levels, as compared to those patients who showed a decrease in hormonal levels in response to exercise, with the baselines exceeding final values.