[New medical technologies in cough therapy: results of a double-blind randomized placebo-controlled multicenter clinical trial].

AIM: To study the efficacy and safety of Eladis® in comparison with placebo in patients with non-productive cough. MATERIALS AND METHODS: A phase III clinical trial enrolled 250 patients aged 18-65 years with acute respiratory viral infection with upper respiratory tract involvement or acute bronchitis. Patients were randomized into 2 groups of 125 subjects: group 1 received Eladis® (40 mg tablets), group 2 received a matching placebo. The patients received the study drugs 1 tablet BID for 7-14 days. After the treatment, patients were followed up (day 7±2) to assess the effect of therapy on the frequency of coughing attacks, the frequency and severity of daytime and nocturnal cough, the severity of cough, the duration of clinical cough cure, and the effect on the severity of the main acute respiratory viral infection symptoms. RESULTS AND CONCLUSION: The results of the study demonstrate the overall efficacy and statistically significant superiority of Eladis® over placebo: there were significant differences between the study groups in the proportion of patients who decreased the coughing attack frequency by ≥50% by day 5 (p<0.0001). In addition, the clinical cure of cough in the Eladis® group occurred 2 days earlier: the median time was 6 days, vs 8 days in placebo group. There was a decrease in the frequency of cough attacks and a decrease in its severity by more than 3.5 points by day 5 of treatment. All the effects were associated with high safety of the drug.

Expression of Genes Encoding Nuclear Factors PPARγ, LXRß, and RORα in Epicardial and Subcutaneous Adipose Tissues in Patients with Coronary Heart Disease.

The nuclear factors PPARγ, RORα, and LXRß are involved in transcriptional control of adipogenesis and implicated in glucose and lipid metabolism. In adipose tissues, they regulate inflammation. This study focuses on expression of the PPARG, RORA, and LXRß (NR1H2) genes in epicardial and subcutaneous adipose tissues in patients with coronary heart disease as well as with concomitant abdominal obesity. In patients with coronary heart disease and abdominal obesity, PPARG mRNA level in subcutaneous adipose tissue was reduced in comparison with control group. In patients with total coronary occlusions, LXRß mRNA level in epicardial adipose tissue was reduced, and it positively correlated with plasma HDL cholesterol. Thus, in cases of concomitant abdominal obesity and chronic total coronary occlusions, coronary heart disease is characterized by down-regulated expression of the genes of various transcriptional adipogenesis-regulating factors in adipose tissue.

[The Expression of Genes Encoding ABCA1 and ABCG1 Transporters and PPARγ, LXRß, and RORα Transcriptional Factors in Subcutaneous and Visceral Adipose Tissue in Women with Metabolic Syndrome].

The study aimed to investigate tissue-specific gene expression of ABCA1 and ABCG1, encoding cholesterol transporters, as well as PPARG, LXRß (NR1H2), and RORA, encoding the most important transcriptional regulators of lipid metabolism, in subcutaneous and visceral adipose tissue (SAT and VAT) in women with metabolic syndrome. It was shown that the ABCG1 mRNA SAT/VAT ratio decreases with age and correlates with the development of metabolic syndrome. After age adjustment, women have reduced chances of metabolic syndrome development when ABCG1 gene expression in SAT is higher relative to VAT than women with VAT ABCG1 gene expression higher or comparable to SAT: OR = 0.15 (95% CI 0.03-0.76), p = 0.023. The ABCA1 mRNA SAT/VAT ratio positively correlated with HDL cholesterol levels (after age adjustment ß = 0.350, p = 0.046), therefore individuals with higher ABCA1 mRNA level in SAT relative to VAT had elevated HDL levels. The ABCA1 mRNA level in SAT was decreased in smokers (p = 0.001). There was a negative correlation between the PPARG mRNA level in SAT with body mass index and waist circumference in the general sample (ß = -0.602, p = 0.003 and ß = -0.642, p = 0.001, respectively, after age adjustment). A decrease of the PPARG mRNA SAT/VAT ratio was associated with elevated plasma insulin level and the insulin resistance index HOMA-IR ß = -0.819, p = 0.004 and ß = -1.053, p = 0.008, respectively, after age adjustment). Thus, the study has shown that the ratio of ABCA1, ABCG1, and PPARG genes expression in different types of adipose tissue (SAT/VAT) could be a significant factor that predicts the development of atherogenic dyslipidemia, metabolic syndrome, and insulin resistance in obesity.

Association of myocardial and serum miRNA expression patterns with the presence and extent of coronary artery disease: A cross-sectional study.

BACKGROUND: MicroRNA (miRNAs) participate in the pathogenesis of coronary artery disease (CAD). OBJECTIVE: To evaluate the expressions of myocardial and serum miRNA-27а, miRNA-133а, and miRNA-203 in CAD patients. METHOD: This cross-sectional observational study comprised 100 subjects (60.9 ± 1.0 years; 67% men). The right atrial and serum expressions of miRNA-27a, miRNA -133a, and miRNA-203 in 80 patients referred for elective coronary artery bypass graft surgery (CABG) and 20 control patients scheduled for heart valve surgery were analyzed using real-time polymerase chain reaction. RESULTS: There was a positive correlation between the SYNTAX score I index and serum miRNA-203 expression level (r = 0.693; p < .001). Patients with ≥3 coronary artery lesions had significantly higher myocardial expressions of miRNA-27a, miRNA-133а, and miRNA-203 than patients with 1-2 vessel disease in the atrial myocardium (miRNA-27a: 234.62 ± 29.51 vs. 182.39 ± 19.62 relative expression unit (REU); miRNA-133а: 127.53 ± 13.41 vs. 111.35 ± 12.31 REU; and miRNA-203: 5.25 ± 0.96 vs. 4.71 ± 0.67 REU; р < 0.05); the same association was found for serum miRNA expressions (miRNA-27a: 11.41 ± 3.85 vs. 4.82 ± 1.82 REU; miRNA-133а: 8.42 ± 2.43 vs. 4.35 ± 1.23 REU; and miRNA-203: 145.71 ± 15.73 vs. 43.70 ± 9.67 REU; р < 0.05). The decision tree method established that the risk of multivessel lesions was increased five-fold if the miRNA-203 serum expression was >101.00 REU (OR, 5.90; 95% CI, 2.34-9.46; p < .001). CONCLUSIONS: Both myocardial and serum miRNA-27а, miRNA-133а, and miRNA-203 expressions are higher in CABG patients than in non-CAD subjects. The serum miRNA-203 expression level corresponds to myocardial expression and is strongly correlated with the extent of coronary atherosclerosis.

[Prognostic value of epicardial fat thickness in coronary heart disease patients after myocardial revascularization].

Objective To study the role of epicardial adipose tissue (EAT) in determination of risk for adverse course of ischemic heart disease (IHD) in patients after myocardial revascularization.Materials and Methods This study included 217 subjects, 182 IHD patients and 35 evaluated individuals without IHD. Percutaneous coronary intervention (PCI) was performed for 104 patients and coronary bypass (CB) was performed for 78 patients. Also echocardiography (EchoCG) and cardiac computed tomography were performed.Results In IHD patients, EAT volume and thickness were greater than in evaluated subjects without IHD. The composite endpoint (CEP) was observed after PCI more frequently than after CB. In IHD patients with an EAT thickness of 8.5 to 10.2 mm measured with EchoCG in the atrioventricular groove, the risk of CEP was 4.3 times higher after myocardial revascularization than with thicker or thinner EAT regardless of the revascularization method.Conclusion An EAT thickness of 8.5 to 10.2 mm in the atrioventricular groove as measured with EchoCG was associated with a risk of adverse IHD course in patients who have underwent myocardial revascularization.

[Epicardial and subcutenious adipose tissue adiponectin gene expression in coronary artery disease patients].

Aim To determine the expression of adiponectin gene (ADIPOQ) and the content of high-molecular-weight adiponectin (HMWA) in epicardial (EAT) and subcutaneous adipose tissue (SCAT) in patients with ischemic heart disease (IHD).Material and methods Paired samples of EAT and SCAT and blood serum were withdrawn from patients with IHD after bypass surgery and 16 subjects without IHD (comparison group). Matrix RNA (mRNA) level was measured using real-time polymerase chain reaction. HMWA levels in EAT and SCAT were evaluated by Western blotting. Serum adiponectin concentration was measured immunoenzymatically. For all patients, echocardiography was performed to measure the EAT thickness; coronarography was performed to determine severity of coronary atherosclerosis.Results Serum adiponectin concentration was lower in IHD patients than in the comparison group (p<0.001). Levels of ADIPOO gene mRNA and HMWA in SCAT were lower in IHD patients than in the comparison group (р=0.020 and p=0.003, respectively). The HMWA level in EAT was lower with the EAT thickness of 8 mm compared to the HMWA level in IHD patients with EAT ≤8 mm (p=0.034).Conclusion The decreased serum concentration of antiatherogenic adiponectin and the reduced expression of ADIPOQ gene in SCAT (mRNA, HMWA) are associated with IHD.

[Common Carotid Intima-Media Thickness, Levels of Total and High-Molecular Weight Adiponectin in Women With Abdominal Obesity].

OBJECTIVE: to investigate influence of different forms of adiponectin on carotid intima-media thickness (CIMT) in women with abdominal obesity (AO) in St.­Petersburg. It has been recognized before that AO is associated with cardiovascular diseases, including atherosclerosis, but mechanism of this association remains unclear. AO leads to imbalance of adipokines, in particularly decrease of adiponectin, which may lead to atherosclerotic lesion of carotid arteries. MATERIALS AND METHODS: We investigated 81 women with AO (IDF criteria, 2005) and 21 women with normal waist circumference. СIMT was evaluated by an ultrasound scanner. RESULTS: Among patients with AO 54.9 % had CIMT >0.9 mm and 38.5 % had atherosclerotic plaques in common carotid arteries. The total adiponectin level (TA) was lower in women with CIMT> 0.9 mm, than in women with normal CIMT (23.20 [2.55; 40.65] and 18.09 [1.60; 38.92] µg/ml, respectively; р0.9 mm, than in women with normal CIMT (2.21 [0.50; 6.85] and 2.88 [1.29; 15.45] µg/ml, respectively; р0.9 mm, than in women with CIMT >0.9 mm and atherosclerotic plaques in carotid arteries (3.09 [1.34; 6.85] and1.82 [0.50; 2.94] mcg/ml, respectively; р0.9 mm depended on waist circumference, diastolic blood pressure and level of C-reactive protein (CRP), while presence of atherosclerotic plaques was associated with levels of HMWA and CRP. CONCLUSIONS: Factors that make the greatest contribution at early stages of atherosclerosis development in carotid arteries in women with AO can be increased waist circumference, high diastolic blood pressure, and high level of CRP. At later stages of atherosclerosis development lowered HMWA level can contribute to the formation of atherosclerotic plaques.

[Safety and Efficacy of Amlodipine, Lisinopril and Rosuvastatin Therapy in Patients With Metabolic Syndrome and Nonalcoholic Fatty Liver Disease].

AIM: To evaluate the efficacy and safety of amlodipin, lisinopril and rosuvastatin therapy in metabolic syndrome and high cardiovascular risk patients with nonalcoholic fatty liver disease (NAFLD). PATIENTS AND METHODS: 6 months randomized study of fixed combination of amlodipin and lisinopril with or without rosuvastatin of 20 patients with 2 grade of arterial hypertension, dyslipidemia with metabolic syndrome and nonalcoholic fatty liver disease (NAFLD). Efficacy and safety was revealed: office BP, ABPM, NAFLD Fibrosis scale, insulin resistance index (HOMA-IR), serum lipids were measured basically and after 6 months of therapy. RESULTS: 6 months amlodipin and lisinopril therapy results: office BP decreased from 153,4+/-2,9/83,3+/-2,5 to 131,0+/-2,4/79,9+/-4,5 mm Hg (=0,001, for systolic BP).159/91 to 132/77 mm Hg. 24-hours BP decreased from 153,6+/-3,6/89,5+/-3,2 to 127,1+/-3,0/73,5+/-2,9 (=0,002); in 85% of patients BP normalized. Low density lipoprotein cholesterol (LDL-C) decreased lower 2.5 mmol/l in all patients and lower 1.8 mmol/l in 45% patients on rosuvastatin therapy. Before therapy 3 patients had elevated ALT levels, after 6 months therapy all patients had normal levels of ALT and AST. ALT decreased from 33,7+/-4,3 to 23,2+/-3,5 U/l (=0,01). Alkaline phosphatase decreased from 65,4+/-4,1 to 51,1+/-6,9 U/l (=0,02), gamma glutamyl transpeptidase level was stable. NAFLD Fibrosis index revealed fibrosis and was stable -0,9+/-0,2 and -0,9+/-0,2 (>0,05). HOMA-IR decreased from 4.2+/-0,4 to 2,9+/-0,4 (=0,02). DISCUSSION: Some antihypertensive drugs and statins can be hepatotoxic especially in patients with metabolic syndrome and NAFLD. Antihypertensive drugs and statins with minimal liver metabolism can be preferable in NAFLD patients. CONCLUSION: Amlodipin, lisinopril and rosuvastatin therapy is effective and safe in patients with metabolic syndrome of high cardiovascular risk and liver steatosis.

Ischemic preconditioning of the rat brain as a method of endothelial protection from ischemic/repercussion injury.

The studies reported here addressed the endothelium-protecting action of local and remote ischemic preconditioning of the brain in rats. Cerebral ischemia lasting 30 min was reproduced by thermocoagulation of the vertebral arteries with simultaneous clamping of the carotid arteries, the procedure being followed by reperfusion via the carotid arteries for 120 min (controls). The early and late phases of ischemic preconditioning and remote preconditioning were reproduced. Brain blood flow was recorded using high-frequency Doppler ultrasonography. The early and late phases of local ischemic preconditioning and the late phase of remote ischemic preconditioning were found to have endothelium-protecting actions apparent as improvements in the recovery of brain blood flow in the post-ischemic period in preconditioned rats, with lower levels of endothelial desquamation and cerebral edema. Blockade of nitric oxide synthesis eliminated the protective effects of both phases of preconditioning.