[Leonid Vasilyevich Sobolev: the first Russian diabetologist, or the History of an unnoticed discovery].

Leonid Vasilyevich Sobolev is an outstanding pathologist, whose name definitely should occupy an honorable place in the galaxy of great scientists of Russia. However, his name was undeservedly forgotten, and the role of his work was underestimated. This Russian scientist made the most important discovery: he proved in an experiment that it is the islets of Langerhans in the pancreas that secrete a humoral regulator, "factor X", the deficiency of which leads to diabetes mellitus. This mysterious islet factor will be isolated from the pancreas of dogs in 1921 by the future Nobel laureate Frederick G. Banting and will become part of the medicine as insulin. However, there is every reason to believe that the discovery of F. G. Banting, who repeated a series of experiments by Leonid Vasilyevich Sobolev, is, in fact, secondary, which is the research subject in this paper.

[Professor D.Ya. Shurygin - the founder of military endocrinology (to the 100th anniversary of his birth)].

In 2023 it would have been 100 years since the birth of a prominent Soviet endocrinologist, Honored Scientist of the RSFSR, chief endocrinologist of the USSR Ministry of Defense (1962-1982), head of the Department of Therapy No. 1 for the improvement of doctors of the Military Medical Academy. CM. Kirov (1972-1982), Professor and Major General of the Medical Service Dorofei Yakovlevich Shurygin.

[Legal regulation of clinical drug trials for the use in military-medical organisations].

The authors identified problematic issues of legal regulation of clinical drug trials for medical use, and proposed possible solutions. It has been established that the conduction of clinical trials, of medicinal products is based on the norms of various branches of law embodied in the Constitution of the Russian Federation, the norms of international law, the Civil Code of the Russian Federation and federal laws and subordinate legislations regulating health and pharmaceutical activity. According to the authors, the norms of bioethics can be attributed to the sources of legal doctrine. It is proposed to oblige executives of clinical trials to make a report about effectiveness and safety of drugs and pass the results to the customer, in his/her turn the customer is obliged to accept the results of these trials and pay for them.

[Thiotriazoline in the Treatment of Stable Angina Pectoris of II-III Functional Class].

Trimetazidine is a metabolic agent of proven efficacy in improving myocardial ischemia and angina. A comparative international multicenter randomized trial, assessed anti-anginal anti ischemic efficacy and safety of Trimetazidine (60 mg/d) and Thiotriazoline (600 mg/d) in symptomatic patients with chronic ischemic heart disease receiving the first line therapy. The study assessed the efficacy of the two drugs on total exercise duration, time to 1-mm ST segment depression, the number of angina attacks and nitroglycerin tablets consumed amount. Both drugs have demonstrated clinical efficacy equal for all primary and secondary endpoints.

[Thiotriazoline in the Treatment of Stable Angina IIIII Functional Class].

Trimetazidine is a metabolic agent of proven efficacy in improving myocardial ischemia and angina. A comparative international multicenter randomized trial, assessed anti-anginal anti ischemic efficacy and safety of Trimetazidine (60 mg/d) and Thiotriazoline (600 mg/d) in symptomatic patients with chronic ischemic heart disease receiving the first line therapy. The study assessed the efficacy of the two drugs on total exercise duration, time to 1-mm ST segment depression, the number of angina attacks and nitroglycerin tablets consumed amount. Both drugs have demonstrated clinical efficacy equal for all primary and secondary endpoints.

Treatment with aliskiren/amlodipine combination in patients with moderate-to-severe hypertension: a randomised, double-blind, active comparator trial.

AIMS: To assess the extent of reduction in blood pressure (BP) of aliskiren/amlodipine combination therapy compared with amlodipine monotherapy in moderate-to-severe hypertensive patients. METHODS: This was an 8-week multicentre, randomised, double-blind study. After a 1-to 4-week washout period, eligible patients [mean sitting systolic blood pressure (msSBP) ≥ 160 to < 200 mmHg] were randomised to receive a once-daily dose of aliskiren/amlodipine 150/5mg (n = 244) or amlodipine 5 mg (n = 241) for 1 week, followed by up-titration to aliskiren/amlodipine 300/10 mg or amlodipine 10 mg for 7 weeks. Efficacy outcome measures included change from baseline to week 8 endpoint in msSBP (primary endpoint), mean sitting diastolic blood pressure (msDBP), and BP control rate (< 140/90 mmHg). Safety was assessed by monitoring and recording all adverse events (AEs) and laboratory abnormalities. RESULTS: Patients' demographic characteristics were balanced between the two groups, mean baseline BP being 171.0/94.3 mmHg for aliskiren/amlodipine and 171.8/95.6 mmHg for amlodipine. Of 485 randomised patients, 433 (89.3%) completed the study. At week 8 endpoint, combination therapy resulted in significantly greater msSBP/msDBP reductions and BP control rate, compared with monotherapy (all: p ≤ 0.0001). The overall incidence of AEs was similar between the two groups. The most commonly reported AE was peripheral oedema with the incidence lower for combination therapy (14.4%) than for monotherapy (18.3%). CONCLUSION: In this population with considerably elevated BP, use of aliskiren/amlodipine combination showed significantly greater BP reductions and allowed more patients to achieve BP control compared with amlodipine monotherapy, with no additional safety concerns.

[Non-invasive assessment of coronary blood flow in veterans of the Ministry of Defence with ischemic heart disease and age-dependent androgen deficiency].

It was examined 51 pensioners of Ministry of Defence with coronary heart disease (average age 55 [52, 59] years). In 20 patients it was verified age-related androgen deficiency, in 31 patients the level of testosterone was within normal limits. The evaluation of coronary circulation was made on single-photon emission tomography with determination of myocardial perfusion in a rest and after pharmacological loading, bicycle exercise test, holter-monitoring of ECG. It was found in 39% cases in patients with coronary heart disease the androgen deficiency in pensioners of Ministry of Defence, that is exceeded the level of common population. Ishaemic changes were found on exercise test in patients with androgen deficiency more often in comparison with patients with normal testosterone level. During myocardial perfusion scintigraphy with adenosine triphosphate there were no differences among group in area of induced coronary heart insufficiency. It was found the negative correlation between the level of testosterone and the duration of ischaemic ST-depression, and positive correlation between testosterone level and tolerance to physical activity.

[Aortic stenosis of alkaptonuric genesis].

Main approaches to intravital diagnosis of alcaptonuria are described. Attention is focused on damages determining invalidisation of patients. A clinical case is presented which demonstrates success of surgical treatment of aortic stenosis of alkaptonuric genesis.

[Frequency and character of violations of cardiac rhythm according to data of intraday monitoring among healthy military servicemen of young age].

For investigation of character and frequency of detection of violations of rhythm and conductivity there was effectuated monitoring of ECG using Holter monitor. In investigation were included 238 military servicemen of young age (23-35 years old), situated in similar conditions of life, chosen according to practical health. Normative indexes of daily variation of arrhythmia were determined using method of non-parametric analyze of qualitative data. On the base of this method, acceptable for using in elaboration of normative values of physiological indexes, the norm could be called isolated cases of ectopic complexes of 5 ventricular and of 24 supraventricular extrasystoles (SVE) for a day. Ventricular extrasystoles (VE) are monotypic, SVE could be polytypic, also could be singular paired complexes. Also could be combination of VE and SVE. Other, more complicated violations of rhythm could be referred either to pathological evidence or to premorbid conditions. Violations of conductivity should be absent in norm.

[Modern tendencies in the treatment of patients with high risk of development of cardiovascular complications and intolerance to angiotensin converting enzyme inhibitors: value of results of TRANSCEND trial for clinical practice].

Clinical value of pharmacologic blockade of renin angiotensin aldosterone system for deceleration of cardiovascular continuum is strongly proved. Up to 20% of population is intolerant to ACE inhibitors. There are no strong evidences that ACE inhibitors differ from angiotensin receptors blockers in influence on main cardiovascular outcomes. In placebo controlled randomized multicentre trial TRANSCEND clinical efficacy, safety and tolerability of telmisartan was studied in elderly patients with high cardiovascular risk who were intolerant to ACE inhibitors. Telmisartan based therapy was associated with decrease of secondary end point (composite of cardiovascular death, myocardial infarction, or stroke) by 13% in comparison with placebo (p=0.048). There were significantly less hospitalizations due to cardiovascular causes in telmisartan group than in placebo group. Risks of new diabetes mellitus, renal dysfunction and serious adverse events were similar in both groups. Combined results of TRANSCEND and PRoFESS trials have demonstrated significant advantage of active telmisartan based therapy concerning the primary outcome of composite of cardiovascular death, myocardial infarction, stroke, or hospitalization for heart failure ( 7%, p=0.026).

[Diabetes mellitus in elderly: comorbid characteristics of patients with different ontogenetic forms of the disease].

Diabetes in elderly is the interdisciplinary problem of diabetology and gerontology. Unlike adults the specific feature of these patients is comorbidities. On the other hand well known is the influence both age and aging on clinical sings of diabetes. The aim of the study was to investigate prevalence and structure comorbid chronic diseases in elderly patients with different ontogenetic forms of diabetes mellitus type 2 (DM2). We examined 169 elderly women with clinical diagnosis "DM2" (mean age--69.8 yrs., mean BMI--29.5 kg/m2, mean HbA1c--7.03%). The stratification was made by ontogenetic stage of diabetes onset and there were five ontogenetic forms of DM2: menstrual (Ms), early-postmenopausal (EPM), late-postmenopausal (LPM), early-involutional (EI) and late-involutional (LI). Anthropometrical, biochemical and immunochemical assays (HbA1c) were made by standard methods. Gognitive index (CGI) and affective index (AFI) were calculated by SCAG scale as mentalmnestic and affective disturbances accordingly. Comorbid index (CI) was calculated as a sum of concomitant diseases. The most comorbid serious was the early-postmenopausal group (CI--6.04 +/- 0.5), mainly by hypertension (92%) coronary heart disease (80%) and osteoarthritis (80%). The lightest comorbid status was in the late-involutional group (CI--4.5 +/- 0.3), with the minimum of gastroenterological diseases (39.5%), kidney diseases (26.3%), thyroid disorders (23.7%) and exclusively the group had valid negative relationship between age and CI (r = -0.550, p = 0.000). As a whole in the elderly diabetic cohort the magnitude of CI correlated positively with BMI (r = +0.344, p = 0.000), frequency of family diabetes (r = +0.204, p = 0.009), AFI (r = +0.161, p = 0.040), menarche (r = +0.175, p = 0.025) and no significantly with CGI (p > 0.05). Thus early ontogenetic forms of DM2 had more comorbidities, especially those with onset DM2 during first 5 years after menopause. And on the contrary, the latest ontogenetic forms with onset DM2 during 20 years after menopause had minimum concomitant diseases. Also early ontogenetic phase (EPM and El) groups had higher magnitudes of CI, frequency of family diabetes and low frequency of familial longevity than late ontogenetic phase (LPM and LI) groups, which allow us to consider early ontogenetic phase DM2 as a phenomena of accelerated aging.

[The light diffusion technique for estimation of the size of urine particles in patients with type 2 diabetes mellitus in the Tamm-Horsfall protein precipitation].

Tamm-Horsfall uroprotein accounts for more than 50% of the urinary proteins in healthy individuals. In abnormalities, it creates a favorable background for detecting smaller-sized uroproteins and for diagnosing pathological processes from the results of native urine tests. In this connection, there is a need for precipitating Tamm-Horsfall glycoprotein while applying laser correlation spectroscopy to analyze the size of urine particles in patients with type 2 diabetes mellitus. Eighty patients with this condition concurrent with different stages of diabetic nephropathy and 23 apparently healthy individuals were examined. The findings suggest that the subfraction urine composition before and after Tamm-Horsfall protein precipitation is different in apparently healthy individuals and patients with type 2 diabetes mellitus concurrent with diabetic nephropathy. This is most likely to be due to the change in the qualitative composition of protein as renal lesion progresses, to the specific features of protein excretion at different stages of a pathological process, and to different concentrations of other low and high molecular-weight proteins.

[Clinical genetic determinants of carbohydrate metabolism disturbances in patients with hypertension and excessive weight].

AIM: To elucidate associations of polymorphic markers of PPAR, PPARG2, IRS1, IRS2 genes with disturbances of carbohydrate metabolism in patients with hypertension and excessive weight. MATERIAL: Patients (n=145, 53 men and 92 women, age 40-75 years) with untreated stage 1 hypertension (systolic BP 140-159 and diastolic BP <100 mm Hg) and excessive weight or obesity (body mass index >27 kg/m(2)) were divided into 2 groups: with (group 1, n=124) and without (group II, n=21) disturbances of carbohydrate metabolism. Group I comprised patients with insulin resistance, abnormal fasting blood glucose or glucose tolerance, type 2 diabetes. Results of oral glucose tolerance test were normal in 25 and abnormal in 99 of these patients. RESULTS: Carriers of Pro allele compared with carriers of Ala allele of PPARG2 gene had higher frequency of insulin resistance. No association was found between insulin resistance and alleles and genotypes of PPAR, IRS1, and IRS2 genes. There was an association between diastolic BP and polymorphic markers Pro12Ala of PPARG2 gene and C24313G of PPARA gene. Carriers of C allele of PPARA gene and Ala allele of PPARG2 gene had higher diastolic BP. No association was found between systolic BP and alleles and genotypes of polymorphic markers of PPARG2 and PPARA genes.

[Significance of pharmacological blockade of angiotensin II type I receptors for correction of abnormal 24-hour blood pressure profile depending on its variability in patients with arterial hypertension stage II]. / Znachenie farmakologicheskoi blokady retseptorov angiotenzina II pervogo tipa dlia korrektsii narushenii sutochnogo profilia arterial'nogo davleniia s uchetom razlichnoi stepeni ego variabel'nosti u bol'nykh arterial'noi gipertoniei 2-i stepeni.

AIM: To specify variable 24-h arterial hypertension (AH) stage II profile and to assess significance of pharmacological block of the end of the renin-angiotensin-aldosteron system for correction of the determined disorders. MATERIAL AND METHODS: The study was made of 46 men (mean age 42.8 +/- 3.28 years) with stage II AH and 25 normotensive controls (mean age 39.2 +/- 3.10 years). Depending on the magnitude of mean 24-h AP variability (APV), hypertensive patients were divided into two groups. Variability of systolic and/or diastolic AP (SAPV and DAPV, respectively) was considered high in at least 15.2 and/or 12.3 mm Hg variability, respectively, and normal at less values. RESULTS: AP 24-h profile in men with AH stage II and high APV compared to patients with normal APV is characterized by higher frequency of AP rise and less frequency of its night fall. In patients with high APV the drug eprosartan (teveten) is more effective in correction of hypertension and night fall of AP. CONCLUSION: Eprosartan has an adequate corrective activity in relation to absolute values of SAP and DAP in different hours. The highest hypotensive activity of the drug was seen in persons with initially high circadian AP variability within 24 hours.

[Circadian variability of cardiac arrhythmias in patients with cardiovascular diseases]. / Sutochnaia dinamika aritmii u bol'nykh s zabolevaniiami serdechno-sosudistoi sistemy.

A total of 1063 results of Holter monitoring in patients with cardiovascular diseases were analyzed. There were regularities in the circadian rhythm of arrhythmias with their decreased values at night and increased ones in the daytime, and peak in the morning. The profile of rhythm depends on the pattern of arrhythmia and cardiac disease. The main oscillators are as follows: sleep-awakening, activity-rest patterns, circadian variations in the sympathetic tone, severity of disease, diurnal variations in myocardial oxygen demand, blood pressure, cardiosclerosis. Conduction disturbances were increased during sleep and early in the morning. Thus, the main unfavourable period in arrhythmia disturbances are early morning, pre- and postawakening periods.

[Aspects of hemodynamics in thyroid dysfunction]. / Osobennossti gemodinamiki pri narusheniiakh funktsii shchitovidnoi zhelezy.

Quantitative electrocardiography, echocardiography and variation pulsometry were used in examination of 231 patients with thyroid dysfunction of various degree. Changes in the central and pulmonary hemodynamics, clinical course, ECG depended on thyroid and thyrotropic blood activity, sympathetic and parasympathetic components of autonomic nervous system. Thyrotoxicosis patients had hemodynamic disorders of the greater and lesser circulation, hypothyroidism patients had only the former.

[Reclid effects on carbohydrate, lipid metabolism, lipid peroxidation and hemodynamics in patients with diabetes mellitus type 2]. / Vliianie reklida na pokazateli uglevodnogo, lipidnogo obmena, perekisnogo okisleniia lipidov i sostoianie gemodinamiki u bol'nykh sakharnym diabetom tipa 2.

Patients with diabetes mellitus type II have disorders in carbohydrate, lipid and other kinds of metabolism. This increases the risk of cardiovascular complications and atherogenesis. Therefore, it is advisable to use drugs preventing an excessive late phase of insulin secretion with resultant reduction of hyperinsulinemia. Reclid, the drug of this group, improves metabolic processes, insulin resistance, lipid metabolism, hemostasis and microcirculation. 3-month reclid therapy of patients with non-insulin-dependent diabetes mellitus produced a good hypoglycemic effect in 85% of the cases. This effect consisted in reduction of basal and postprandial glycemia, levels of glycosylated hemoglobin, 24-h glucosuria. In patients with diabetes mellitus type II reclid diminished the levels of total cholesterol, triglycerides, glycosylated hemoglobin. In patients with left ventricular diastolic dysfunction, reclid improved transmitral blood flow. Thus, reclid provides a good metabolic control in patients with non-insulin-dependent diabetes mellitus. Moreover, it positively affects mechanisms initiating cardiovascular complications in diabetic patients.