[Meta-analytic assessment of parenteral cytoflavin effectiveness in different neurologic disorders]. / Metaanaliticheskaia otsenka klinicheskoi éffektivnosti tsitoflavina pri nevrologicheskikh zabolevaniiakh.

AIM: To carry out an integral quantitative assessment of the clinical efficacy of parenteral use of cytoflavin in treatment of patients with CNS disorders based on the systemic selection of published controlled clinical trials and their meta-analysis. MATERIAL AND METHODS: Twenty-one high evidence-based studies on the efficacy of parenteral use of cytoflavin in different CNS disorders (4314 patients) have been analyzed. Comparisons with basic treatment groups were undertaken to clarify the drug clinical effects adjusted for heterogeneity and variability of response parameters. RESULTS AND CONCLUSION: An analysis of formalized efficacy indicators (increase in the absolute and relative value, odds ratio (OR) etc.) has demonstrated the advantages of cytoflavin. Group combination has increased the statistical power of the meta-analysis. Two models with fixed (Mantel-Haenszel amendment) and random effects were used. All the estimation protocols in different clinical groups of patients with neurologic diseases provided similar results and confirmed the stability of calculated values irrespective of heterogeneity of data arrays. OR of positive outcomes in neuropathologies treated with cytoflavin was 3,02 with χ2 heterogeneity 427,3 and p = 0,000…, I2= 85,7% (82%; 88%).

Antiplatelet Therapy of Cilostazol or Sarpogrelate with Aspirin and Clopidogrel after Percutaneous Coronary Intervention: A Retrospective Cohort Study Using the Korean National Health Insurance Claim Database.

BACKGROUND/OBJECTIVES: Addition of cilostazol or sarpogrelate to the standard dual antiplatelet therapy of aspirin and clopidogrel has been implemented in patients that underwent percutaneous coronary intervention (PCI) with stents in Korea. This study aimed to evaluate the efficacy and safety of triple antiplatelet therapies. METHODS: This retrospective cohort study was performed using the Korean National Insurance Claim Data of the Health Insurance Review and Assessment Service from January 1, 2009 to December 31, 2014. The study cohort population consisted of patients with ischemic heart diseases and a history of PCI. They were treated with antiplatelet therapy of aspirin, clopidogrel (AC); aspirin, clopidogrel, cilostazol (ACCi); or aspirin, clopidogrel, sarpogrelate (ACSa) during the index period from January 1, 2010 to December 31, 2011. During the follow-up period up to December 31, 2014, the major adverse cardiac or cerebral events (MACCE) including death, myocardial infarction, target lesion revascularization, and ischemic stroke were assessed. Bleeding complications were also evaluated as adverse drug events. RESULTS: Out of 93,876 patients with PCI during the index period, 69,491 patients started dual (AC) or triple therapy (ACSa or ACCi). The clinical outcomes of comparing ACSa and ACCi therapy showed beneficial effects in the ACSa group in the prevention of subsequent cardiac or cerebral events. After Propensity score-matching between ACSa and ACCi groups, there were significant differences in MI and revascularization, with corresponding HR of 0.38 (95% CI, 0.20-0.73) and 0.66 (95% CI, 0.53-0.82) in ACSa vs. ACCi at 12 months, respectively. At the 24-month follow-up, the triple therapy groups (ACS or ACC) had a higher incidence of MACCE compared to the dual therapy (AC) group; ACSa vs. AC HR of 1.69 (95% CI, 1.62-1.77); ACC vs. AC HR of 1.22 (95% CI, 1.06-1.41). There was no significant difference in severe or life-threatening bleeding risk among three groups; ACSa vs. AC, HR of 0.68 (95% CI, 0.37-1.24), ACCi vs. AC, HR of 0.91 (95% CI, 0.77-1.09). CONCLUSION: Sarpogrelate-containing triple antiplatelet therapy demonstrated comparable rates of MACCE prevention to the conventional dual antiplatelet therapy after PCI without significantly increasing bleeding risk during the two-year follow-up period.

[ASSESSMENT OF SPECIFIC PHARMACOLOGIC ACTIVITY OF UNIFUSOL ON ENDOTHELIUM DYSFUNCTION MODEL INDUCED BY N-NITRO-L-ARGININE METHYL ETHER.]

Specific pharmacologic activity of sodium-L-arginine succinate (unifusol) was studied on endothelium dysfunction model (EDM) in rats. EDM was induced by daily administration of N-nitro-L-arginine methyl ether (L-NAME). The effectiveness of experimental therapy with unifusol was assessed by changes in the arterial pressure level, duration of endothelium-dependent and -independent vasodilation, and the blood concentration of endothelial dysfunction markers including VEGF, NO, endothelin-I and the number of desquamated endotheliocytes. Administration of unifusol favors correction of blood vessel endothelium state manifested by normalization of its functional activity and reduction of the apoptosis of endotheliocytes. In addition, the obtained results unambiguously confirm considerable vasodilating and antihypertensive effects of unifusol.

[Pharmacoeconomic Analysis of the Use of Hepatoprotectors in Management of Drug-Associated Liver Injury Due to Hodgkin's Lymphoma Chemotherapy].

The data on the pharmacoeconomic research of the use of Remaxol in treatment of drug-associated liver injury due to the chemotherapy in cancer patients are presented. The costs-efficiency method was applied to two groups of the patients with drug-associated liver injury treated according to different schemes. The research showed economical benefits of the Remaxol use.

[Assessment of multimodal effect of cytoflavin in the acute brain stroke in patients with metabolic syndrome].

Sixty patients were randomized to treatment with cytoflavin (n=30) or nootropil (n=30). Patients of the main group received cytoflavin along with standard treatment for correction of hemodynamics. The treatment scheme was as follows: intravenous injections during 10 days, tablets - from 11 to 35 days. The same scheme of treatment was used in the comparison group. The total duration was 35 days. Patients were assessed with NIHSS, the Rankin scale, the Barthel index, MMSE. MRI was used to verify ischemic lesions. The therapeutic efficacy of cytoflavin was significantly higher compared to nootropil in respect to the restoration of neurological functions and self-service abilities as well as to the reduction of cognitive deficit.

[Effectiveness of the hepatoprotective activity of reamberine, remaxol, and ademethionine and risk assessment in their use in patients with respiratory tuberculosis and drug-induced liver injury].

AIM: To comparatively evaluate the hepatoprotective activity of reamberine, remaxol, and exogenous ademethionine and a risk for unfavorable/favorable outcomes of their use in patients with liver injury during antituberculosis chemotherapy. SUBJECTS AND METHODS: One hundred and eighty patients with new-onset respiratory tuberculosis were examined and divided into 4 groups (45 patients in each group): Study Group 1 (SG1): patients who took reamberine; Study Group 2 (SG2): those who received remaxol; Study Group 3 (SG3): those who had ademethionine; and a Comparative Group (CG): those who received 5% glucose solution. The test drugs were intravenously administered in a dropwise manner once daily for 10 days. The laboratory hepatic injury severity index (LHISI) was estimated according to the method described by T.N. Kalachnyuk and the risk for a favorable/unfavorable outcome was assessed, by calculating the average cost of the used hepatotropic agents. RESULTS: LHISI increased statistically significantly with the development of liver injury induced by antituberculosis agents. There was a statistically significant reduction in LHISI during therapy with the test hepatotropic agents versus glucose solution, the most pronounced activity being shown by remaxol. Relative risk (RR) and odds ratio (OR) assessments revealed the high likelihood of a favorable outcome (a reduction in LHISI) when each of the 3 test drugs versus glucose solution was administered; the highest RR and OR were also found in the use of remaxol. Estimation of costs and the number of patients to be treated (NPBT) in order to avoid a case of none LHLIS reduction could reveal the highest efficacy of remaxol. CONCLUSION: The test agents (reamberine, remaxol, and ademethionine) are effective in treating tuberculosis patients with drug-induced liver injury. The administration of remaxol demonstrated the highest positive effect (as estimated by LHISI) in terms of both RR and NPBT.

Safety assessment of a novel ingredient for removable chewing gum.

Rev7 is an indigestible gum polymer used for the manufacturing of chewing gum. It allows for the formulation of chewing gum with low adhesion; thus can be readily removed from surfaces such as sidewalks, clothing, carpets and furniture. In a toxicological safety assessment, Rev7 was found to be non-mutagenic in the AMES assay. The highest concentration tested in a mouse lymphoma thymidine kinase locus gene mutation assay induced a slight but biologically relevant increase in mutations under non-metabolic activation conditions after 24h. Because of this finding, a mouse micronucleus assay was performed, and the test article was found to be negative for inducing chromosomal damage. A 28-day repeated oral toxicity study resulted in a NOAEL of 80,000 ppm; the highest concentration tested. Rev7 was found to be free from contaminants such as heavy metals, monomers, and solvents. Lastly, Rev7 did not demonstrate skin-sensitizing properties in the murine local lymph node assay.