[Comparative study of the clinical efficacy and safety of the fixed dose combination Levroso Long with Melaxen and Diphenhydramine in patients with insomnia]. / Rezul'taty sravnitel'nogo klinicheskogo issledovaniya effektivnosti i bezopasnosti kombinirovannogo lekarstvennogo preparata Levroso Long s preparatami Melaksen i Dimedrol u patsientov s bessonnitsei.

OBJECTIVE: Evaluation of the efficacy and safety of Levroso Long (fixed dose combination (hereinafter referred to as «FDC¼) diphenhydramine and melatonin, 25 mg + 3 mg and FDC diphenhydramine and melatonin 50 mg + 3 mg, respectively, capsules with modified release, NovaMedica Innotech LLC) in comparison with diphenhydramine medicines 50 mg (Diphenhydramine tablets, DALHIMFARM OJSC, Russia) and 3 mg melatonin (Melaxen tablets, Unipharm Inc., USA) in patients with insomnia. MATERIALS AND METHODS: Material and methods. A multicenter open randomized comparative clinical trial was conducted in parallel groups. The study included 312 patients with an insomnia diagnosis verified in accordance with the DSM-IV criteria (ICD code F51.0-10) and an insomnia severity index (ICI) >8 points. The patients were randomized into 4 groups and took the following medications for 10 days: patients of group 1 - Levroso Long (25 mg diphenhydramine and 3 mg melatonin), group 2 - Levroso Long combination drug (50 mg diphenhydramine and 3 mg melatonin), Group 3 -Diphenhydramine 50 mg, 4th - Melaxen 3 mg. A comparative assessment was performed on the 7th and 10th days of therapy according to the primary endpoint - ICI, and secondary endpoints - the results of the assessment based on the Leeds Sleep Assessment Questionnaire, the Pittsburgh Sleep Quality Questionnaire, the Scale of the overall clinical impression of improvement and the analysis of the profile of adverse events (NA). RESULTS: The FDC of diphenhydramine 25 mg + melatonin 3 mg was more effective than diphenhydramine 50 mg, and FDC diphenhydramine 50 mg + melatonin 3 mg was more effective than diphenhydramine 50 mg or melatonin 3 mg on both primary and secondary endpoints. In a safety assessment, the highest incidence of adverse events (48.7%) in the diphenhydramine 50 mg group was significantly lower in groups 1 (29.5%), 2 (12.8%) and 4 (1.3%). All reported adverse events in the FDC groups were mild or moderate in severity. CONCLUSION: The study showed that Levroso Long in two dosages surpassed monotherapy with 50 mg of Diphenhydramine (50 mg) or Melaxen (3 mg) in patients with insomnia in terms of efficacy parameters. The benefit/risk ratio of the studied drug is favorable compared to monotherapy.

[The results of phase III multicenter open randomized controlled study REM-Chol-III-16 in patients with intrahepatic cholestasis syndrome caused by chronic diffuse liver diseases].

AIM: To assess the safety and efficacy of Remaxol, solution for infusion, compared with parenteral form of S-adenosyl-L-methionine, in the treatment of patients with intrahepatic cholestasis syndrome accompanying chronic diffuse liver diseases of various etiology. MATERIALS AND METHODS: In a multicenter open-label comparative study of the safety and efficacy of Remaxol (inosine + meglumine + methionine + nicotinamide + succinic acid) 317 patients aged 18 to 65 years were randomized into 2 groups: patients of the experimental group (n=168) received intravenous Remaxol, solution for infusion, 400 ml, and patients of the control group (n=149) Heptral (S-adenosyl-L-methionine) 800 mg. The duration of treatment was 10 days. The primary efficacy endpoint was the proportion of patients who responded to therapy, as demonstrated by dynamics of laboratory parameters of liver functional status: decrease in gamma glutamyl transpeptidase level by 40%, and/or alkaline phosphatase level by 30%, and/or decrease total bilirubin level by 30% from baseline by the end of the treatment course. RESULTS: The proportion of responders was 51% in the Remaxol group vs. 44.9% in the Heptral group (p=0.303); the lower limit of the one-sided 95% confidence interval for the difference in the proportions of responders was -4.01%, which exceeds the non-inferiority margin pre-defined by the study protocol, thus, the non-inferiority hypothesis was proven, i.e. Remaxol at a dose of 400 ml/day demonstrates similar efficacy to Heptral at a dose of 800 mg/day in patients with intrahepatic cholestasis syndrome associated with chronic diffuse liver diseases. Similar positive trends in the levels of transaminases, total bilirubin and the severity of pruritus were revealed in both treatment groups. We did not reveal statistically significant between-group differences in the frequency of adverse events definitely related to the study treatment. CONCLUSION: Administration of Remaxol as a part of the pathogenetic therapy of patients with intrahepatic cholestasis syndrome who need hepatoprotection is justified.

[INFLUENCE OF LIPOSUCTION OF LARGE VOLUME ON SYSTEMIC AND LUNG CIRCULATION, OXIGENATED LUNG FUNCTION].

The authors measured the changes of hemodynamics in 72 patients. It was also estimated a blood oxygenation and volume of liquid sectors of the organism in different degree of obesity before and after liposuction of the large volume. It was shown, that this operation facilitated to an improvement of respiratory lung function due to changes of pulmonary circulation.

[Role of intrarenal product TNF-alpha in the development of glomerular and tubulointerstitial tissues changes in elderly patients with diabetic nephropathy].

The aim of this study was to investigate the expression of TNF-alpha produced in the kidney in patients with diabetic nephropathy (DN) type 2 diabetes and its impact on the development of glomerular and tubulointerstitial tissue changes in these patients. The survey was conducted in 49 elderly patients (mean age 66.53 +/- 3.50 years) with type 2 diabetes complicated by the development of DN. The study included patients with serum creatinine less than 0.13-0.14 mmol/l and in the initial stage of chronic renal failure in the level of serum creatinine less than 0.20 mmol/l. Diabetes duration was 17.89 +/- 0.44 years, and the duration of diabetic nephropathy was 1.60 +/- 0.44 years. Light and immunofluorescence microscopy of the renal biopsy specimens obtained by needle lifetime biopsy was performed for all patients. Morphological changes in the tissue were assessed in accordance with the latest international classification of diabetic nephropathy. In addition to light and immunofluorescence microscopy the expression of TNF-alpha in the glomerulus and interstitial tissue by monoclonal antibodies labeled Fitc ("Dako", Germany) were determined in all patients. The location of TNF-alpha expression in the glomeruli (capillary loops, mesangial matrix, glomerular capsule) and in the interstitial tissue (urinary epithelium convoluted tubule basement membrane of urinary tubules, interstitial cells) were estimated. Correlation analysis of the influence of the expression of TNF-alpha on the expression of morphological changes of tissues revealed that a maximum of cytokine production in the glomeruli at the stage IIa class cytokine affected only the development of segmental glomerular sclerosis. With the decrease in TNF-alpha production in the glomeruli you can observe the progression of histological changes--periglomerulyarny sclerosis development, builds thickening of the glomerular basement membrane; mesangial expansion goes from mild to severe and affects more than 25% of mesangial matrix (IIb stage), nodular lesions of Kimmelstil-Wilson are forming. Interstitial produce of TNF-alpha remains relatively high in the epithelium of the urinary tubules and in the interstitial cells of the kidney regardless of the class of diabetic nephropathy and influence the development of tubulointerstitial fibrosis.

[Mathematical model of removal of impurities from antibiotic pastes]. / Matematicheskaia model' protsessa osvobozhdeniia past antibiotikov ot primesnykh veshchestv.

The process of antibiotic paste washing by repulpation in a solvent, as well as the process of replacing washing of antibiotic filter cakes was studied. This enabled to develop a mathematical model of the process of admixture removing from antibiotic pastes by successive repulpation and replacing washing. The model connects the initial admixture levels in pastes, the filter cake characteristics, the specification requirements to the drug quality and the technological parameters of the process. The results of the studies confirmed the model adequacy.

[Stability of rifamycin B in aqueous solutions]. / Ustoichivost' rifamitsina B v vodnykh rastvorakh.

Stability of rifamycin B in aqueous solutions at various values of pH and temperature was studied. It was shown that inactivation of the antibiotic in neutral and alkaline solutions proceeded according to the first order equation. In acid solutions rifamycin B was oxidized with air oxygen to form rifamycin O.

[Rifamycin in B distribution between aqueous and organic phases]. / K voprosu o raspredelenii rifamitsina B mezhdu vodnoi i organicheskoi fazoi.

Dependence of the coefficient of rifamycin B distribution in the system of butyl acetate-buffer solution on pH of the equilibrium acqueous phase, antibiotic concentration in the solution and temperature was studied. It was shown that the coefficient value did not depend on the antibiotic concentration within 1000-2000 gamma/ml and temperature.