[Association of the structure of the glucocorticoid receptor and single nucleotide NR3C1 gene polymorphisms with metabolic disorders].

Glucocorticoid therapy is widely used in the treatment of various pathologies. Sensitivity to glucocorticoids  (GC) has a serious impact not only on the effectiveness of their action, but also on the severity of side effects, the formation of risk factors and the development  of cardiovascular diseases (CVD). Variability of sensitivity to GC causes different phenotypes and severity of metabolic disorders underlying  CVD. Among  them, one can distinguish  a decrease in muscle mass and strength, obesity, glucose and lipid metabolism impairment, and others. Glucocorticoids carry out their effects by binding to the glucocorticoid receptor (GR), and therefore this is considered a critical point in their action. This review presents data on the significance of the glucocorticoid  receptor structure, examines the main single nucleotide polymorphisms (SNP) of the NR3C1 gene associated with hypersensitivity  or relative resistance to glucocorticoids  in the context of metabolic disorders and the development of CVD. The association of the four most studied SNP of the GR gene with metabolic risks is described in detail: BclI (rs41423247), N363S (rs56149945), ER22/23EK (rs6189/rs6190), GR-9ß (rs6198). Their determination can contribute to clarifying the prognosis of both the effectiveness of GC and the development of metabolic disorders, and subsequent early correction of CVD risk factors.

Clinical significance of lipohypertrophy without visual and palpable changes detected by ultrasonography of subcutaneous fat.

AIM: To estimate clinical significance of lipohypertrophy (LH) without visual and palpable changes, detected by ultrasonography of subcutaneous fat. MATERIALS AND METHODS: This study included 140 diabetic patients who received insulin in basal-bolus regimen. Ultrasonography of subcutaneous fat was performed for LH diagnostics in these diabetic patients. Than clinical significance of LH without visual and palpable changes was estimated. HbA1c level, fasting and postprandial glucose, episodes of hypoglycemia, body mass index (BMI) and scheme of insulinotherapy were evaluated at the moment of LH, after 3 and 6 months in all patients. RESULTS: After changing injection sites, good results were demonstrated by measuring glucose and HbA1c level. Thus fasting glucose decreased from 9.03±1.98 mmol/l to 7.11±0.95 mmol/l (p=0.023). Postprandial glucose reduced from 10.27±2.72 mmol/l to 9.34±1.21 mmol/l (p=0.011). HbA1c level reduced from 9.27±1.75% to 7.43±1.02% (p=0.002). Also BMI decreased from 33.75±3.49 kg/m2 to 30.5±2.96 kg/m2 (p=0.018). CONCLUSION: LH without visual and palpable changes could worsen compensation of glycemic control and leads to hypoglycemia and chronic Somogyi rebound. So, LH without visual and palpable is as important and clinically significant as classic LH.

[Correlation of parameters of carbohydrate metabolism and saturated fatty acids in blood serum in elderly people.]

The study involved 106 elderly people of the Arctic aged 61-74 years, 42 of them were residents of the Subarctic region (SR) and 64 residents of the Arctic region (AR). Using gas-liquid chromatography there was determined the serum content of saturated fatty acids (SFA): short-chain (SCFA), medium-chain (MCFA) and long-chain (LCFA); and the levels of carbohydrate metabolism parameters were determined by spectrophotometric methods. Correlation analysis showed that elderly people of SR had no significant interrelationships between the contents of SCFA, MCFA and LCFA, since all the correlation dependences were weak (r=0,2-0,29, p=0,08-0,786), against AR with a lower occurrence of high values of glucose (Glu), lactate (Lac) and low pyruvate (Pyr). In AR, with the highest occurrence of high and low values of GIu, the greatest number of its interrelations was noted with LCFA (palmitic, margarine, stearic, behenic, tricosanoic), then with MCFA (myristic, pentadecanoic) and SCFA (pelargonic), low values of Pyr with MCFA (lauric, myristic, ∑MCFA) and SCFA (decanoic), and a slight decrease in the occurrence of high levels of Lac and Lac/Pyr with LCFA (palmitic, margarine, stearic, tricosanoic), MCFA (lauric, tridecanoic) and SCFA (caproic, capric).

[Nonalcoholic fatty liver disease: What do we know and what will we have to learn?] / Nealkogol'naia zhirovaia bolezn' pecheni: chto my znaem i chto predstoit uznat'.

The article reviews relevant data on the prevalence, natural history, pathogenesis, diagnosis, and treatment of nonalcoholic fatty liver disease and critically assesses the fixed notion of this disease.

[Association between depression and metabolic syndrome--a two-way street].

The study with the use of the CES-D scale revealed the combination of depression and metabolic syndrome in 24% of the examined patients. The HADS scale showed depression in 16% of the interviewed patients. Based on the two scales, depression was documented in 32% of the patients. The chance of development of metabolic disorders in case of depression was estimated as 2.4 (95%); CI--1.3-4.6. Urinary 6-COMT level at 4.00 correlated with its total nocturnal and daytime concentrations and with sleep disorders (r = -0.41; r = -0.48; r = -0.43 respectively). Daytime sleepiness correlated with the daytime 6-COMT level (r = -0.32). The score values by the CES-D scale correlated with daytime 6-COMT level (r = -0.23). Multiple regression analysis showed that reduced melatonin level deteriorates quality of nocturnal sleep and increases the risk of depression (R = 0.4. coefficient ß = -0.413 (p<0.04) and F = 4.5).

[The content of apolipoproteins in blood M and parameters of lipid metabolism in population of North Polar regions and Southern regions of Caucasus].

The study was carried out concerning the between content of apolipoproteins A and B in blood and lipid metabolism in population of North Polar regions and Southern regions of Caucasus. The differences of correlation relationships depending on concentration of apolipoproteins A and B in blood in population dwelling in territories climate geographic regions were detected.

[Microalbuminuria as a marker of endothelial dysfunction in the long-term follow-up patients after surgical correction of aortic coarctation].

1170 patients after surgical correction of aortic coarctation during the period from 1988 to 2002 were studied. The median period of medical supervision after coarctation repair was 13,8 years, maximum age - 24 years. For diagnostics of the Microalbuminuria (MAU) it were used the special test-strings Microalbu PHAN (PLIVA-Lachema Diagnostica). MAU were discovered in 62.6% of and 34.9% of normotesive patients. Credible decrease of MAU of hypertensive patients with corrected coarctation of the aorta were defined after 3 months-long treatment by Losartan.

[Melatonin and metabolic syndrome: is there an association?].

The basis for the current view of the mechanisms for regulating metabolic processes is the hypothesis proposed by the United Kingdom scientists E. Scott and P. Grant that evolutionary fixed adaptation to seasonal environmental changes is impaired. Under the hypothesis, impairment in seasonal and circadian rhythms is the key condition for the occurrence of obesity, arterial hypertension (AH), and type 2 diabetes mellitus. The diseases of civilization, namely obesity, insulin resistance, and AH, are a direct result of chronic metabolic disturbance due to light pollution.

[Melatonin as a regulator of metabolism].

High prevalence of metabolic syndrome (MS) necessitates elucidation of its causes. Disturbed melatonin synthesis is supposed to be one of them. This work was aimed at studying melatonin (M) secretion in MS and its influence on the main symptoms of MS. It was shown that melatonin production decreases at 4 a.m. and increases in the afternoon when it is correlated with waist circumference, insulin and LDLP levels (+0.28, -0.30, -0.44). M secretion in the morning correlates with blood glucose level and mean daily AP (-0.37, -0.22). Correlation of M secretion at 4 a.m., in the afternoon and at night with MS parameters was described by coefficients R equaling 0.79, 0.75 and 0.74 respectively. It is concluded that the intragroup risk of MS development is 2.9 and increases when M secretion is disturbed.

[Arterial hypertension and metabolic disorders].

Combination of arterial hypertension (AH) and metabolic disorders accelerates development of organic lesions in target organs. As shown in recent prospective studies, myocardial hypertrophy rate closely correlated with severity of metabolic disturbance. The thickness of interventricular septum and posterior wall show stronger dependence of severity of metabolic disorders than left ventricular density while left atrial enlargement is correlates with fasting glycemia and excess body mass. There is close relationship between microalbuminurea and hyperinsulinemia and the number of metabolic syndrome components is linearly correlated with glomerular filtration rate below 60 ml/min. It is shown that rigidity of arteries is a new independent risk factor of cardiovascular complications in obese patients. Moreover, metabolic disturbances cause affective disorders that impair quality of life and therapy motivation. Combination of AH, metabolic disturbances, and borderline psychic disorders dictated consideration of abnormal melatonin secretion as a condition developing as a consequence of disturbed adaptive circadian rhythms. This hypothesis was prompted by the discovery of the so-called "clock genes" in the central nervous system and practically all peripheral organs including heart, vessels, and adipose tissue.

[Antihypertensive treatment compliance and obstacles to its improvement. Results of Russian program ARGUS-2].

AIM: To study barriers made by the patients for adequate treatment of arterial hypertension. MATERIAL AND METHODS: The ARGUS-2 trial was made in 15 centers of 13 cities of Russia. Anonymous questionnaire survey covered 1298 patients (796 outpatients and 502 inpatients). The patients answered the following questions: 1) what are basic problems of life with hypertension; 2) compliance with intake of antihypertensive drugs; 3) causes of missed intakes of the drugs; 4) opposition to intake of drugs by the patients. Questioning procedure was preset by the trial protocol. RESULTS: Only 37.4% (38.9% outpatients, 34.6% inpatients) were the treatment adopters. Drug intake was missed most frequently because offorgetting. The problems of life with hypertension were differently interpreted by patients and physicians: for the latter main problems were financial and routine while AH complications were on the 6-7 place. The latter were of primary importance for the patients while financial problems took place 4-6 Barriers to regular intake for the patients were poor self-control and unawareness about side effects of the drugs. CONCLUSION: Complience of the patient can be improved only by complex approach: improvement of education, higher motivation, active involvement of patients into the treatment process, better contacts between the physician and the patient.

[Problems of a physician-patient interaction and control of arterial hypertension in Russia. Main results of scientific-practical program ARGUS-2].

OBJECTIVE: To study the problems of physician-patient cooperation, patient- and physician related barrieres to target blood pressure (BP) achievement and to demonstrate improvement of BP control with indapamide SR 1.5 mg, when given to patients remaining uncontrolled while receiving antihypertensive therapy without thiazide diuretics (TD). METHODS: The trial Improvement of Arterial Hypertension Control in High-Risk Hypertensive Patients (ARGUS-2) run in 15 Russian centres during the year 2006. Retrospective analysis of medical notes of 684 outpatients and 575 inpatients with arterial hypertension. Validated questionnaires were used for interview of 373 physicians and 1298 patients. The study of Arifon retard efficacy was carried out in 1438 outpatients with difficult-to-control hypertension. RESULTS: BP was above the goal level in 97.1% pts at the first analyzed visit to an outpatient department. Antihypertensive therapy was unchanged in 20.5% cases, the drug dose was increased in 46,6%, additional medication was administered in 36,8%. In 30.8% pts antihypertensive agent was substituted by another class drug. At the last analyzed visit target BP was found in 24.4% pts. BP control was poorer in pts with BP goal <130/80 mmHg (20.1%) than in those with higher target BP (25.9%). Achievement of BP goal was associated with combination therapy, higher rate of TD administration and with more frequent visits to physician. During hospitalization target BP <140/<90 mmHg was achieved in 87.1%,<130/<80 mmHg in. 76.2%. Arifon retard administration resulted in target BO achievement in 84.5% patients. Physicians percept low adherence to antihypertensive treatment, lack of patients knowledge about risk related to arterial hypertension, economical problems as main barriers to improvement of arterial hypertension management. Patients considered economical problems related to antihypertensive treatment more much less important than physicians did. CONCLUSION: The study results suggest the importance of therapeutic inertia overcome to improve arterial hypertension management in Russia. Low rate of multiple combination therapy and TD prescription are important features of therapeutic inertia. Polar perception of problems related to arterial hypertension by physicians and patients should be considered as influencing factors for educational programs development.

[Effect of therapy with lisinopril on the state of cerebral blood flow in women with hypertension in peri- and postmenopause]. / Vliianie terapii lizinoprilom na sostoianie tserebral'nogo krovotoka u zhenshchin s arterial'noi gipertenzieiv peri- i postmenopauze.

Blood flow in extra and intracranial arteries was assessed by doppler ultrasound in 26 hypertensive women without history of stroke. Studies were performed before treatment, after acute test with lisinopril and in 1 month of therapy with lisinopril. Baseline investigation revealed changes of velocity characteristics of blood flow and resistance indexes indicative of impaired cerebral hemodynamics both at extra- and intracranial level. After treatment with lisinopril signs of improvement of blood flow in extra- and intracranial arteries were found. Most important finding was normalization of ability of extracranial arteries to spasm and dilation presumably associated with restoration of hemodynamic reserve of cerebral vessels.

[Stratification of patients with hypertension and selection of antihypertensive therapy]. / Stratifikatsiia bol'nykh s arterial'noi gipertenziei i vybor antigipertenzivnoi terapii.

Patients with hypertension (78 men, 113 women aged 20-73 years) were stratified according to risk of development of cardiovascular complications. In low and moderate risk patients (n=31) with borderline hypertension, dyslipidemia and pronounced obesity mainly non-drug measures were employed directed at lowering of excess body mass. Medium risk patients (n=25) with isolated hypertension group were treated with angiotensin converting enzyme inhibitors and phenylalkylamine calcium antagonists. High risk patients (n=55) with metabolic syndrome received same antihypertensive drugs as medium risk patients. In very high risk patients (n=79) with diabetes, excessive body mass, dyslipidemia and proteinuria complex therapy consisting of antihypertensive and hypoglycemic drugs and non-drug interventions was used. This risk stratification based management of patients with hypertension on turned out to be highly effective and resulted not only in normalization of blood pressure but also in improvement of carbohydrate and lipid metabolism, lowering of resistance to insulin and excessive body mass, and improvement of renal function.

[Ednit effects on activity of renin-angiotensin-aldosterone system and renal function in hypertensive subjects with diabetes mellitus]. / Vliianie édnita na aktivnost' renin-angiotenzin-al'dosteronovoi sistemy i funktsiiu pochek u bol'nykh arterial'nymi gipertoniiami v sochetanii s sakharnym diabetom.

AIM: To evaluate effects of enalapril (ednit) therapy on activity and reactivity of renin-angiotensin-aldosteron system (RAAS) and renal function. MATERIALS AND METHODS: Ednit was given in a dose 5-10 mg/day to 30 patients with mild or moderate arterial hypertension (AH) in combination with moderate or severe non-insulin-dependent diabetes mellitus (NIDDM) in compensation or subcompensation of carbohydrate metabolism. RESULTS: Ednit lowered blood pressure after 6-7 days of treatment. Normal blood pressure was achieved on the treatment week 4-6. Antihypertensive effect of ednit resulted from a significant reduction in a total peripheral vascular resistance under unchanged cardiac output. Adequate hypoglycemic and antihypertensive therapy normalized carbohydrate metabolism. Renal elimination of nitrogen did not change much. Glomerular filtration rate in patients with hyper- and hypofiltration returned to normal. Proteinuria reduced, microalbuminuria was not registered. RAAS activity normalized. CONCLUSION: Ednit has both high antihypertensive activity and marked renoprotective effect with minor influence on carbohydrate metabolism in AH patients with NIDDM.

[Metabolic effects of quinapril in hepertensive patients]. / Metabolicheskie éffekty kvinaprila u bol'nykh arterial'nymi gipertoniiami.

AIM: The study of antihypertensive and metabolic effects of quinapril (accupro) in patients with essential hypertension (EH). MATERIALS AND METHODS: Serum levels of cholesterol, its fractions and triglycerides were measured and standard glucose tolerance test was made in 40 EH patients before accupro therapy and 1 and 3 months after continuous accupro treatment (10-20 mg/day). RESULTS: Antihypertensive effect of accupro was accompanied by marked improvement in carbohydrate and lipid metabolism in 28 patients. Normalization of blood pressure in the absence of negative effect of accupro on parameters of carbohydrate and lipid metabolism was recorded in 12 patients free of coexisting metabolic disorders. CONCLUSION: The results of the trial allow to recommend antihypertensive treatment with accupro as effective both in patients with metabolic disorders and free of them.