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The article describes some characteristics of temperature homeostasis regulation while intraoperative period and its correction methods by infusions of balanced crystalloid solutions on the basis amino acids and the Krebs cycle substrates., Materials and Methods: 107 children of different ages were included into the study. All of them underwent surgery on thoracic or abdominal organs. The average age was 13 (7-16) years. All the operations were performed with total intravenous anesthesia and artificial lung ventilation. 0,9% sodium chloride solution, "Mafusol" "Infezol-40" and "Reamberin" were used in order to correct perioperative hypothermia. Results of the study. It was found that solutions based onfumarate (mafusol) and succinate (reamberin) have a significant positive effect on the temperature homeostasis. This fact means they can be recommendfor a broad usage in clinical practice for the purpose ofprevention and elimination of intraoperative hypothermia.

The aim of the study was to evaluate the effectiveness of cytoflavin in the complex treatment of patients with diabetic foot syndrome., Material and Methods: The research is based on the results of a comprehensive survey of 140 people with diabetic foot syndrome. Depending on the treatment, all patients were divided into 2 groups. The first group (n=35) received basic therapy. The second group (n=35) in addition to basic therapy received cytoflavin 10 ml (+200 ml 0.9% NaCl) for 10 days, followed by switching to the tablet form of the drug 2 tablets twice a day for 1 month., Results: Analyzing the severity of polyneuropathy after treatment, we noted a more positive dynamic in patients who in addition to standard therapy received cytoflavin.

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%).

Aim: To improve the results of treatment of patients with acute small bowel obstruction., Material and Methods: The research is based on the results of a comprehensive survey 202 people with acute small bowel obstruction. Reamberin was used in 102 patients treatment., Results: It was established that metalloenzymes take an active part in the formation of endotoxemia in people with acute small bowel obstruction. Also, in patients as a result of an imbalance between oxidant and antioxidant systems, accumulated a significant amount of lipid peroxidation products, along with it a decrease activity of enzymes of antioxidant system. reamberin application in complex treatment of acute small bowel obstruction provided the reduction in the time correction of oxidative stress by preventing the growth and activity of lipid peroxidation products with simultaneous stimulation of the antioxidant system and contributed to the normalization of microelement homeostasis.

Aim: The purpose of the study was to study the effectiveness of the domestic drug Remaxol in reparative processes of laparotomic wound tissues in acute surgical abdominal pathology in patients with diabetes mellitus., Material and Methods: Clinical and laboratory studies were performed in 86 patients with acute surgical pathology of the abdominal cavity, 56 patients with type 1 diabetes mellitus, including 26 patients who received Remaxol in the early postoperative period (daily intravenous infusions of 400.0 ml for 5 days)., Results: It was established that diabetes mellitus is an important aggravating factor in the reparative process of tissue structures of a laparotomic wound. Undoubtedly, a significant factor in reducing the reparative potential of tissues is a significant activation of factors leading to membrane-destabilizing phenomena - oxidative stress, activation of phospholipases, hypoxia. The inclusion of Remaxol, which has antioxidant and antihypoxic effects, allows to significantly correct these pathogenetic components, which is the basis for optimization of the reparative process against the background of diabetes mellitus. There was a significant decrease in wound complications in the early postoperative period, a significant reduction in the stay of patients in the hospital.

Aim: To evaluate the efficacy of cytoflavin in the correction of functional state and working ability of Navy operators after a long working cycle., Material and Methods: Results of the examination of 25 Navy operators, aged from 27 to 42 years, were analyzed at baseline and after treatment with cytoflavin. The Rusalov questionnaire for Individuality Formal Dynamic Properties and EEG were used to evaluate the state of participants., Results and Conclusion: The results demonstrate the ability of cytoflavin to exert the positive effect on the energetic component of the functional state of Navy operators after a long working cycle, increasing the psychomotor activity and optimizing the spontaneous electrical activity of the brain. The activation of energetic potential, physical activity and emotional reactions by cytoflavin is correlated with the growth of the central nervous system reserves in Navy operators treated after a long working cycle.

Curcumin diethyl disuccinate (CDD) is a succinate prodrug of curcuminoids that has better stability in human plasma and improved in vitro cytotoxicity compared to curcumin. Therefore, CDD has the potential for further development as an anticancer agent. In this study, we focused on optimization of the formulation of CDD-loaded chitosan/alginate nanoparticles using Box-Behnken statistical design to enhance the therapeutic efficacy of CDD. Oil-in-water emulsification followed by ionotropic gelification was used to prepare the CDD-loaded chitosan/ alginate nanoparticles. A formulation with a 0.05:1 chitosan/alginate mass ratio, 0.65% (w/v) Pluronic F127 and 1.5 mg/ml CDD was found to be optimal. FTIR, TGA and XRD confirmed the encapsulation of CDD molecules in the nanoparticles. In vitro cytotoxicity and cellular uptake studies showed that CDD-loaded chitosan/alginate nanoparticles had significantly higher cytotoxicity and cellular uptake in human breast adenocarcinoma MDA-MB-231 cells, compared to free CDD. Physical and chemical stability studies indicated that the optimally formulated CDD-loaded chitosan/alginate nanoparticles were stable at 4 °C for 3 months.

Background and Objectives: Curcumin is the major bioactive component of turmeric, but has poor oral bioavailability that limits its clinical applications. To improve the in vitro solubility and alkaline stability, we developed a prodrug of curcumin by succinylation to obtain curcumin diethyl disuccinate, with the goal of improving the oral bioavailability of curcumin., Methods: The in vivo pharmacokinetic profile of curcumin diethyl disuccinate was compared with that of curcumin in male Wistar rats. Doses of curcumin 20 mg/kg intravenous or 40 mg/kg oral were used as standard regimens for comparison with the prodrug at equivalent doses in healthy adult rats. Blood, tissues, urine, and faeces were collected from time zero to 48 h after dosing to determine the prodrug level, curcumin level and a major metabolite by liquid chromatography-tandem spectrometry., Results: The absolute oral bioavailability of curcumin diethyl disuccinate was not significantly improved compared with curcumin, with both compounds having oral bioavailability of curcumin less than 1 %. The major metabolic pathway of the prodrug was rapid hydrolysis to obtain curcumin, followed by glucuronidation. Interestingly, curcumin diethyl disuccinate gave superior tissue distribution with higher tissue to plasma ratio of curcumin and curcumin glucuronide in several organs after intravenous dosing at 1 and 4 h. The primary elimination route of curcumin glucuronide occurred via biliary and faecal excretion, with evidence of an entry into the enterohepatic circulation., Conclusion: Curcumin diethyl disuccinate did not significantly improve the oral bioavailability of curcumin due to first pass metabolism in the gastrointestinal tract. Further studies on reduction of first pass metabolism are required to optimise delivery of curcumin using a prodrug approach.

Sarpogrelate is an antiplatelet agent widely used to treat arterial occlusive diseases. Evaluation of platelet aggregation is essential to monitor therapeutic effects of sarpogrelate. Currently, no molecular signatures are available to evaluate platelet aggregation. Here, we performed comprehensive proteome profiling of platelets collected from 18 subjects before and after sarpogrelate administration using LC-MS/MS analysis coupled with extensive fractionation. Of 5423 proteins detected, we identified 499 proteins affected by sarpogrelate and found that they strongly represented cellular processes related to platelet activation and aggregation, including cell activation, coagulation, and vesicle-mediated transports. Based on the network model of the proteins involved in these processes, we selected three proteins (cut-like homeobox 1; coagulation factor XIII, B polypeptide; and peptidylprolyl isomerase D) that reflect the platelet aggregation-related processes after confirming their alterations by sarpogrelate in independent samples using Western blotting. Our proteomic approach provided a protein profile predictive of therapeutic effects of sarpogrelate., (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)

Aims/introduction: Our previous study found that dexamethasone-induced insulin resistance (IR) was involved in 5-hydroxytryptamine (5-HT) synthesis and 5-hydroxytryptamine 2 receptor (5-HT 2 R) in the periphery. The present study examined the effects of inhibitions of both peripheral 5-HT synthesis and 5-HT 2 R on dexamethasone-induced IR., Materials and Methods: Male rats were exposed to dexamethasone for 10 days, then treated with or without a 5-HT 2 R antagonist, sarpogrelate, a 5-HT synthetic inhibitor, carbidopa, alone or in combination for 20 days., Results: Dexamethasone-induced whole-body IR, with glucose intolerance, decreased insulin sensitivity, hyperglycemia, hyperinsulinemia and dyslipidemia, could be effectively abolished by sarpogrelate or/and carbidopa, whereas IR-related actions of dexamethasone in tissues were accompanied by increased 5-HT synthesis in the liver and visceral adipose, and upregulated 5-HT 2 R (5-HT 2 A R and 5-HT 2 B R) expression in these two tissues as well as in skeletal muscle. Sarpogrelate or/and carbidopa treatment significantly abolished dexamethasone-caused tissue-specific IR. In the liver, increased gluconeogenesis, triglycerides and very low-density lipoprotein syntheses with steatosis, and downregulated expression of plasmalemmal glucose transporter-2 were markedly reversed. In the visceral adipose and skeletal muscle, downregulated expression of plasmalemmal glucose transporter-4 was significantly reversed, and increased lipolysis was also reversed in the visceral adipose. Dexamethasone-induced activations of hepatic mammalian target of rapamycin serine 2448 , and S6K threonine 389/412 phosphorylation were also abolished markedly by sarpogrelate or/and carbidopa. Co-treatment with sarpogrelate and carbidopa showed a synergistic effect on suppressing dexamethasone actions., Conclusion: Inhibitions of both peripheral 5-HT synthesis and 5-HT 2 R are expected to be a dependable target for treatment of steroid-induced diabetes., (© 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

The bombesin analogue, [(99m)Tc-GGC]-(Ornithine)3-BN(2-14), (99m)Tc-BN-O, targeting gastrin releasing peptide receptors (GRPrs) on the surface of tumors, was pre-clinically investigated as potential imaging agent for single photon emission computed tomography (SPECT). In addition, the improvement of its pharmacokinetic profile (PK) was investigated through the co-administration of a succinylated gelatin plasma expander (Gelofusine), aiming to reduce its kidney accumulation and enhance its tumor-to-normal tissue contrast ratios. Biodistribution data were collected from normal mice and rats, and PC-3 tumor bearing mice, in reference to its PK, metabolism and tumor uptake. Imaging data were also collected from PC-3 tumor bearing mice. Biodistribution and imaging experiments showed that (99m)Tc-BN-O was able to efficiently localize the tumor (5.23 and 7.00% ID/g at 30 and 60min post injection, respectively), while at the same time it was rapidly cleared from the circulation through the kidneys. HPLC analysis of kidney samples, collected at 60min p.i. from normal mice and rats, showed that the majority of radioactivity detected was due to intact peptide i.e. 56% for mice and 73% for rats. Co-administration of (99m)Tc-BN-O with Gelo resulted in the reduction of kidney uptake in both animal models. The integrated area under the curve (AUC30-60 min) from the concentration-time plots of kidneys was decreased in both mice and rats by 25 and 50%, respectively. In PC-3 tumor bearing mice, an increase of tumor uptake (AUCtumor increased by 69%) was also observed with Gelo. An improvement in tumor-to-blood and tumor-to-normal tissue ratios was noted in all cases with the exception of the pancreas, which normally expresses GRPr. The results of this preclinical study may also be extended to other similar peptides, which are utilized in prostate cancer imaging and present similar PK profile., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The Aim: a synthesis of evaluations ofReamberin's clinical efficacy as energy protectorfor the results of a meta-analysis of published data obtained during controlled clinical studies with the same design and a high level of evidence., Materials and Methods: To estimate succinic acid based remedy for infusions (reamberin), the meta-analysis was undertaken with data of reamberin use in intensive care, resuscitation departments, in critical post surgery period, in oncology (multiple chemotherapy of tumors), in emergent toxicology and pediatrics. 32 controlled randomized trials and all together 6221 patients were included., Results: Unified indicators of clinical efficiency were systemically and thoroughly processed with advanced statistic tools, resulting data were sufficient for association and assessment of their heterogeneity in different articles. The adjuvant effects of reamberin were proven, as good outcome frequency enlarged more than by 25%, absolute and relative treatment benefits increased more than by 50%, positive outcome chance grew twice and more., Conclusions: According to sensitivity analysis and this meta-analysis results reamberin may be positioned as adjuvant energetic protector valid to improve effectiveness of pharmacologic correction during the treatment of emergencies joint with hypoxia, energy deficiencies and vegetative disregulations.

Porcine reproductive and respiratory syndrome virus (PRRSV), a common viral pathogen, causes huge annual economic losses to the swine industry worldwide. After triggering by specific ligands, the Toll-like receptor 7 (TLR7), a type of pattern-recognition receptor (PRR), induces antiviral cytokines production. Previously, we synthesized an adenine analog, designated SZU101, a TLR7-specific ligand. In this study, we assessed the inhibitory effect of SZU101 on PRRSV infection in vitro. SZU101 significantly suppressed PRRSV infection in primary porcine alveolar macrophages (PAMs) in a dose-dependent manner. Moreover, SZU101-induced inhibition involved NF-κB pathway activation in PAMs to initiate expression of TLR7-mediated cytokines and induce expression of downstream signaling IFN-stimulated genes (ISGs). Chloroquine, a TLR7 inhibitor, and BAY 11-7082, an NF-κB inhibitor, reversed both the SZU101-induced antiviral effect and induction of cytokine genes and ISGs expression. Therefore, SZU101 antiviral effects depend at least in part on TLR7-NF-κB signaling pathway. Additionally, administration of SZU101 enhanced the humoral and cell-mediated immune responses against PRRSV antigens in mice. Given these results, SZU101 holds promise as an antiviral agent and a vaccine adjuvant to prevent PRRSV infection in pigs., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The Aim: to study the effect of solution with methionine "Remaxol" on metabolic disorders andfat embolism developing in severe combined trauma., Materials and Methods: 544 patient with severe skeletal trauma were undergone to a prospective study of dynamics of fat embolism syndrome development depending on the inclusion in the program of infusion therapy drug "Remaxol". The dynamics of lactate, glucose, free fatty acids, globularia and the incidence offat embolism syndrome were analyzed., Results: Corrective action drug with methionine "Remaxol" on hyperglycemia, hyperlactatemia, hyperlipemia and de- crease circulation offat globules, which is reflected in the decrease in the frequency of development offat embolism syndrome was identified., Conclusion: One of the proposed mechanisms reduce the risk offat embolism development is assumed restoration of endogenous carnitine synthesis with methionine and transport offree fatty acids in the cell and their subsequent inclusion in metabolic processes.

This study was aimed at revealing clinical and laboratory peculiarities in the health of married couples suffering of pregnancy miscarriage and the possibility of correcting this state by preconception therapy with reamberin, based on analysis of the results of observations and investigations for 196 married couples. At the first stage, we have studied the influence of provoking factors on the miscarriage during first trimester, including the presence and degree of chronic nonspe- cific intoxication. The patients were divided into groups: first (main) group including 40 couples, in which the pregnancy was complicated by the risk of pre- gnancy termination in the first trimester and second (comparison) group of 74 couples, in which abortion in the first trimester was followed by complex precon- ception therapy. The control group included 82 couples with normal course of pregnancy in the first trimester. At the second stage, we have studied the efficacy of including reamberin in the scheme of therapy. For this purpose, patients in the second (comparison) group were separated into subgroups. In subgroup I, 50 male patients received reamberin (i.v., dropwise, 400 mL per day at a rate of 60 - 70 drops/min, over 10 days), while 24 male patients of subgroup II were treated according to commonly accepted schemes (involving recommendations concerning regime and diet, psychological aid, and polyvitamins in prophylac- tic doses). Analysis of the obtained data revealed the presence of nonspecific intoxication in patients of the main group comparison groups, which was related to the increased level of intermediate metabolism products and osmotic state of plasma, and disorders in the hepatobiliary system as manifested by hyperbiliru- binemia, increased level of transaminases, urea, creatinine, etc. In addition, most patients also exhibited changes in spermograms, including astenozospermia (75.9 ? 7.9%) and teratozospermia (69 ? 8.6%) on the background of relative androgenous insufficiency, and bacterospermia in 26.7 ? 8.1% of patients from couples where the pregnancy of females was complicated by risk of miscarriage in the first trimester, and in 34.3 ? 5.8% of patients from couples receiving re- habilitation care upon abortion in the first trimester. The inclusion of reamberin in the scheme of complex preconception therapy of male in pairs with miscarri- age problems increased the efficacy of therapy. This was manifested by decrease in the parameters of intoxication (on the average by 21 % (d = 0.017), positive dynamics of the main indices of spermograms, and improvement of the general state, which led in turn to increased probability of the onset and maintenance of pregnancy.

Aim: To study an efficacy of Reamberine in complex therapy in early postoperative period after knee-joint surgery., Material and Methods: It was analyzed treatment of 108 patients (47 men and 61 women) with degenerative diseases of knee-joint in postoperative period. Periarticular osteotomy of tibia and knee-joint replacement were performed. Patients were divided into 2 groups. Main group consisted of 43 patients who received Reamberine 400-800 ml with infusion rate 4-5 ml/min during 1-1,5 hours for 4-8 days postoperatively. Control group (65 patients) had conventional therapy with daily volume 400-800 ml., Results: It was revealed that Reamberine increased efficacy of postoperative treatment. There were earlier (by 52.6% compared with control group) improvement of health including weakness disappearance, sleep and appetite recovery. Hemodynamic parameters were also improved (stabilization of blood pressure and pulse). It was observed earlier disappearance of pain and edematous syndrome (by 32.3%). There were also earlier postoperative wound healing (by 21.3%) and reducing of rehabilitation terms (by 72%, i.e. 2.1 ± 0.7 vs. 7.5 ± 0.9 days respectively).

The aim of this study was to investigate the efficiency of metabolic therapy in correction of cognitive impairment in patients with type 2 diabetes. We undertook the analysis of results of the treatment of cognitive dysfunction in 80 patients with a diagnosis of type 2 diabetes. All patients received basic hypoglycemic therapy. 32 patients (study group) received in addition to the basal glucose lowering therapy daily intravenous infusion of 10 mlcytoflavindiluted in 200 ml of a 0.9% sodium chloride solution for 10 days, followed by 2 tablets b.i.d. for 25 days.The group of comparison consisted of 29 patients given in addition to the basal glucose-lowering therapy daily intravenous infusion of 24 ml (600 mg) thioctacid diluted in 200 mL of a 0.9% sodium chloride solution for 10 days. Thereafter, they received 1 tablet of thioctacid BV once daily for 30 days. The control group consisted of 19 patients who received basic hypoglycemic therapy without additional metabolic therapy.Inclusion of cytoflavin in the combined treatment of patients with type 2 diabetes ensured a more effective correction of cognitive impairment. There was a statistically significant improvement in optical-spatial activities (p = 0.001), attention (p = 0.001), abstract thinking (p = 0.046), and memory (p<0.001) compared to those in other groups, according to the MOS test. Positive dynamics was expressed as the improvement of the optical-spatial activities by 9,8 ± 10,3%, attention by 13,5 ± 11,8%, abstract thinking by 7,0 ± 8,9%, and memory by 23.0 ± 14 6%. The study of variations of the serum level of brain neurotrophic factor (BDNF) over time during the treatment with metabolic preparations reveal edits statistically significant increase (p = 0.002) in the patients treated with cytoflavin compared with comparison (p = 0.139) and control (p = 0.078) groups. These results suggest the influence of cytoflavin on the processes of neuroplasticity under conditions of hyperglycemia, improvement of cerebral microcirculation and cerebroprotective action of this medication.

After 100 extensive resections of a liver for excision of metastasises of a colorectal cancer, the different drugs protecting a liver were used for prophylaxis of a liver failure., Material and Methods: Patients were distributed on 2 equivalent groups. Patients of the first group received Ademetionin in a dosage 400 mg 2 times a day within 7 days. Patients of the second group received Remaxol in a dosage 400 ml within 7 days once a day., Results: Frequency of cases of an acute liver failure in the first group of patients was 38%, in the second group of patients - 20% (p<0.05). Patients of the second group had milder course of an acute liver failure (by criteria of ISGLS, 2011) in comparison with patients of the first group. Postoperative bed - days in the first group of patients lasted 13 (11-15) days, in the second group of patients - 11 (10-13) days (p<0.05). There was no postoperative lethality.

Aim: To evaluate the impact of incorporating cytoflavin in a treatment regimen for patients with different stages of hypertensive disease (HD)., Subjects and Methods: The results of treatment were analyzed in 140 patients with HD (53 with Stage I, 50 with Stage II, and 37 with Stage III). According to the treatment regimen, the patients were divided into 2 groups. A study group (n=74) received combination treatment involving antihypertensive therapy and cytoflavin intravenously dropwisely in a single dose of 200 ml of 5% glucose solution for 10 days, then 2 tablets twice daily for 60 days, with a total cycle time being 70 days. A comparison group (n=66) had antihypertensive therapy only. Thirty apparently healthy individuals (a control group) were examined to have reference values. All the patients were examined using conventional clinical and laboratory studies. The patients' complaints and neurological status were assessed using respective questionnaires over time - before and after treatment., Results: The incorporation of cytoflavin in a treatment regimen was ascertained to reduce the degree of anxiety, depressive, dissomnic, and cognitive disorders, improves quality of life in patients with Stage I HD, and lowers the degree of asthenic and autonomic disorders in all disease stages., Conclusion: The found efficacy and safety of the drug may recommend its incorporation in combination therapy regimens for Stages I-III HD.

The study was aimed to investigate the influence of drug reamberin inclusion in the treatment regimen of patients with acute Epstein-Barr virus (EBV) infection on the effectiveness of therapy. Treatment results were analyzed in a group of 70 children aged 4-15 with a diagnosis of moderate to severe EBV infection. By the method of random sampling distribution, patients were divided into two comparable groups of 35 children, which were representative with respect to gender, age, date of admission, and conducted basic therapy. Patients in the control group were treated by the conventional scheme, while the main group received basic therapy with antibacterial drug (according to indication) and symptomatic agents (antipyretics, desensitizing agents, and local antiseptics for the treatment of rotor and nasopharynx) and, in addition, obtained 1.5% reamberin solution intravenously, 10 mL/kg body weight once a day at a rate of 3-4 mL/min (the treatment course did not exceed 3 days). Treatment efficacy was assessed by a decrease in the duration of intoxication symptoms, relief of their clinical manifestations, and normalization of laboratory data (including, in addition to commonly accepted data, the levels of malonic dialdehyde, ferritin, transferrin and catalase before and after treatment).The inclusion of reamberin in the therapy of acute EBV infection in children favors (in comparison to conventional treatment regimen) more pronounced and rapid decrease the intensity of the oxidative process and improves the functioning of the antioxidant system. This was manifested by normalization of immunobiochemical indicators (reduction of malonic dialdehyde and ferritin and increase in the level of catalase) and decrease in the inflammatory response (leukocytosis, ESR, and the number of atypical mononuclear cells in the blood), This resulted in more rapid relief of the clinical manifestations of infection (sore throat, hyperthermia, lymphadenopathy, and hepatomegaly) and shortened the hospital stay by 38.5% (p < 0.05).

Aim: To study an effect of reamberin and α-lipoic acid (α-LA) on the tolerance of mice with experimental diabetes mellitus (DM) to acute cerebrovascular accident (ACVA) in mice experiments., Material and Methods: The authors studied mice with alloxan diabetes and subtotal and total brain ischemia. In additional experimental series, an effect of reamberin and α-lipoic acid on the tolerance to acute hypoxic hypoxia and intensity of hyperglycemia in experimental DM was studied., Results and Conclusion: The increased vulnerability of animals to ACVA due to hyperglycemia and increased sensitivity to acute hypoxic hypoxia was established. Reamberin and α-lipoic acid administered for 14 days in doses, which are equivalent to therapeutic range in humans, enhance the tolerance to ACVA and acute hypoxic hypoxia in mice with alloxan diabetes. These medications also decrease the intensity of hyperglycemia during concurrent insulin replacement therapy. The increased tolerance to ACVA in mice with alloxan diabetes caused by reamberin and alpha-lipoic acid is associated with an antihypoxic effect of these medications and does not depend on their effect on the intensity of hyperglycemia. Reamberin outperformed α-lipoic acid in the antihypoxic activity, protection against ACVA and the rate of onset of glucose reducing effect in experimental diabetes mellitus.

The authors studied the efficiency of the expansion of the standard course of conservative therapy of deforming coxarthrosis by appointment Cytoflavin and behavioral therapy. The study was performed on 104 elderly patients. It was found that the addition of the existing scheme increases the effectiveness of therapeutic interventions, which manifests itself as the improvement of the mental and physical components of quality of life by reducing pain and increasing the functionality of some of the affected hip. At the heart of positive clinical effect is a decrease in processes of inflammation and reduction of tension of regulatory processes in the organism. Positive quality extra medical appointments was the absence of significant side effects when taken orally Cytoflavin requiring discontinuation of the drug, as well as the absence of failure patients from further sessions of behavioral therapy.

Aim: To evaluate the efficiency of Remaxol monotherapy in patients with nonalcoholic fatty liver disease (NAFLD) at the stage of steatohepatitis (SH)., Materials and Methods: The treatment of 156 patients with NAFLD at the stage of SH was analyzed. A study group included 84 patients who had received intravenous Remaxol, 400 ml, dropwise at a rate of 40-60 drops per minute once daily in the morning for 10 days; a control group of 72 patients had been treated with the conventional scheme., Results: During the treatment, the study group showed a rapider relief of the manifestations of asthenovegetative and dyspeptic syndromes and a reduction in the magnitude of biochemical manifestations of cytolytic and cholestatic syndromes than did the control group., Conclusion: Incorporation of Remaxol into the therapy regimen in patients with NAFLD at the stage of SH enhances the effectiveness of treatment.

Aim: To investigate the effect of Remaxol on the efficiency of standard treatment in patients with infiltrative pulmonary tuberculosis (IPT)., Materials and Methods: The results of treatment were analyzed in 90 patients with new-onset IPT in the phase of decay who received basic tuberculosis treatment regimens I, IIb, and IV. In addition, a study group of 45 patients used dropwise intravenous Remaxol 400 ml daily and a control group 45 patients had dropwise intravenous 5% glucose solution 400 ml daily. All the patients underwent clinical, laboratory and instrumental (X-ray) examinations over time., Results: The incorporation of remaxol into the combination treatment of IPT enhanced the efficiency of therapy, which manifested as reductions in the hepatotoxicity of etiotropic drugs and in the degree of dysproteinemia and as accelerated destructive regression in tuberculous infiltrates with a subsequent decrease in the need for phthisiosurgical care. Remaxol included into the standard complex treatment regimens for IPT contributed to the rapider normalization of laboratory parameters of the liver and to the accelerated regression of destructive changes in the tuberculous infiltrates., Conclusion: Incorporation of remaxol into the combination treatment of patients with IPT enhances the efficiency of its therapy, promotes the rapider normalization of laboratory indices of the liver and the accelerated regression of destructive changes in tuberculous infiltrates, which reduces the need for phthisiosurgical care.

Aim: To study the effectiveness of remaxol in erythrocytes oxygen transport function correction in patients with surgical endotoxicosis., Material and Methods: Two groups of patients (main (n = 25) and comparison (n = 27) groups) with acute appendicitis complicated by peritonitis were compared. All patients underwent standard postoperative treatment including infusion therapy 1600--2000 ml/day, antibiotics as combination of semi-synthetic penicillins and aminoglycosides, anesthetic and desensitizing therapy. In the main group daily intravenous infusion of remaxol 400 ml for 5 days was used. The first dose was administered intraoperatively or immediately after surgery. Patients underwent emergency surgery and destructive forms of acute appendicitis accompanied by diffuse purulent or purulent-fibrinous peritonitis were diagnosed. Removal of appendix, debridement and drainage of the abdominal cavity were performed. Observation of clinical and laboratory tests were carried out at admission and in 1, 3, 5 days after surgery., Conclusion: Acute peritonitis leads to changes of hemoglobin conformation and its oxygen-binding capacity according to spectroscopy that is an important factor in the development of general hypoxia. The greatest changes in the hemoglobin molecule were found in the 1st day after surgery as a result of surgical aggression. It is proved that modified conformational state of hemoglobin is associated with processes of lipid peroxidation and endogenous intoxication. Combined therapy with remaxol is effective to correct oxygen transport function of hemoglobin in acute peritonitis. Pronounced positive effect of the drug weakening manifestations of surgical aggression is noted after the first administration. Therapeutic efficacy of the drug is explained by its ability to reduce lipid peroxidation. Rapid recovery of homeostasis including decrease of general hypoxia using remaxol resulted in a clinical benefit.

The aim of the study was to assess the effectiveness of cytoflavin inclusion in complex treatment of patients with hypoparathyroidism occurring after thyroid surgery. To do this, an analysis of treatment of 54 patients who received surgical treatment for thyroid diseases of various etiologies. Depending on the scheme of post-operative medical therapy, the patients were divided into 2 groups: group I patients (27 persons) received basic therapy according to regulatory documents, II of the group (27 patients) in addition cytoflavin intravenous drip of 10 ml to 200 ml 0.9% NaCl for 7 days. In addition to standard clinical and laboratory examination, all patients were studied and the level of active ionized Ca2+ and PTH, oxidation products of the modified protein, lipid peroxidation and antioksidazation system dynamics - 1, 3 and 7 days after surgery. It was revealed that in the first days after the surgical treatment of patients significantly reduced the levels of ionized Ca2+ and PTH that may be regarded as signs of postoperative hypoparathyroidism, as well as the activation of the system of lipid peroxidation and antioxidant system depression. Turning cytoflavin in drug regimens improved the efficiency of the treatment, which was manifested in arresting to 7 days of monitoring signs of hypoparathyroidism, improve tissue oxygenation and restoring the balance by reducing the activity of the system of lipid peroxidation and antioxidant system strengthening.

The aim of the study was to increase the efficiency of the treatment of acute ethanol intoxication in patients with alcoholic fatty liver disease. The article presents the results which received during the investigation and treatment of 166 patients with acute ethanol in- toxication on the background of alcoholic fatty liver disease Patients were assessed by the severity scale APACHE-Il. Were studied the dynamics of clinical, laboratory, biochemical parameters, the state of the antioxidant system activity and lipid peroxidation. The study found the effect of the combination hepatoprotective drug remaxol on the many links of metabolism, which was confirmed by the dynamics of biochemical parameters. There was a quick correction of hyperlactatemia, an effective reduction of ALT activity, the absence of reduction of albumin and urea concentration in the somatic period of ethanol poisoning. Period of using remaxol there was improvement in the clinical course of the disease, which manifested by the reduce the incidence of delirium tremens and shorten the duration of treatment of patients.

To significantly promote tumor uptake and penetration of therapeutics, a nanovehicle system comprising poly(lactic-co-glycolic acid) (PLGA) as the hydrophobic cores coated with pH-responsive N-acetyl histidine modified D-α-tocopheryl polyethylene glycol succinate (NAcHis-TPGS) is developed in this work. The nanocarriers with switchable surface charges in response to tumor extracellular acidity (pHe) were capable of selectively co-delivering indocyanine green (ICG), a photothermal agent, and doxorubicin (DOX), a chemotherapy drug, to tumor sites. The in vitro cellular uptake of ICG/DOX-loaded nanoparticles by cancer cells and macrophages was significantly promoted in weak acidic environments due to the increased protonation of the NAcHis moieties. The results of in vivo and ex vivo biodistribution studies demonstrated that upon intravenous injection the theranostic nanoparticles were substantially accumulated in TRAMP-C1 solid tumor of tumor-bearing mice. Immunohistochemical examination of tumor sections confirmed the active permeation of the nanoparticles into deep tumor hypoxia due to their small size, pHe-induced near neutral surface, and the additional hitchhiking transport via tumor-associated macrophages. The prominent imaging-guided photothermal therapy of ICG/DOX-loaded nanoparticles after tumor accumulation induced extensive tumor tissue/vessel ablation, which further promoted their extravasation and DOX tumor permeation, thus effectively suppressing tumor growth.

Aim: The purpose of the research was to study the effectiveness of enteral insufficiency correction at an acute peritonitis by applying minimally invasive techniques, electrical stimulation and rehabilitation of the bowel and abdominal intestine using Remaxol drug., Material and Methods: The analysis of the results of clinical and laboratory examination and treatment of 110 patients with acute diffuse peritonitis. In the comparison group (62 patients) in the early postoperative period applied standardized treatment, including software reorganization of the abdominal cavity, in the study group (48 patients) -- a comprehensive treatment that includes software laparoscopic sanation abdominal electrical stimulation of the duodenum, and intra-abdominal (single dose, 200 ml), and intracolonic (200 ml, 2 times daily) administration Remaxol. It was noted a significant improvement in treatment outcomes, including reduced mortality by 2.3 times, the shortening of hospital stay by 1.3 times., Results: The major component of the positive effect of the developed scheme of therapy is its ability to promptly arrest the effects of enteral insufficiency, maintain the functional status of the liver. The relatively rapid recovery of motor and intestinal barrier function leads to a lowering of enteral insufficiency syndrome, which along with increased liver detoxification ability underlies the significant reduction of endogenous intoxication in three days. An important contribution to the effectiveness of the treatment makes intra and intracolonic administration Remaxol. The drug, possessing antioxidant, antihypoxic, hepatoprotective effects, contributes to the relatively rapid improvement of the barrier function of the peritoneum and intestines, detoxification ability of the liver recovery that significantly contributes to the relief of endogenous intoxication.

Aim: The aim of the study was to assess the effectiveness of the inclusion in the scheme remaxol treatment of metabolic syndrome in patients with nonalcoholic steatohepatitis and diabetes mellitus 2 type., Materials and Methods: Data of 76 patients with metabolic syndrome in a non-alcoholic steatohepatitis and type 2 diabetes were analyzed. Patients were randomized by gender and age, and are divided into 2 groups according to the scheme of therapy: patients in group I (major - 38) conducted a basic therapy in combination with remaxol: intravenous infusion of 400 ml of 1 times a day for 10 days, group II patients (comparison - 38) combined basic therapy with intravenous ademetionine: 400 mg, in a solution diluted NaCL 0,9% 400 ml 1 time per day for 10 days. In addition to standard clinical and laboratory tests were studied biochemical parameters of liver activity, lipid and carbohydrate metabolism in the dynamics: before therapy and after its completion., Results: It was found that the inclusion in the scheme of drugs from the group of succinates (remaxol) reduces the severity of metabolic syndrome by reducing the manifestations of cholestasis and cytolysis, and improving lipid and glucose metabolism. As a result, significantly reduced the severity of the main clinical syndromes: asthenovegetative 46% and dyspeptic syndromes - 46% and 15%, respectively.

The purpose of this study was to evaluate the efficacy of Reamberin as a component of intensive care edematous form of acute pancreatitis in elderly and senile patients. There were analysed the treatment data of 78 patients of this category diagnosed with «acute pancreatitis edematous form». Based on the regimens, patients were divided into 2 groups: 42 patients of the main group received Reamberin in addition to the standard treatment; patients in the control group (36 patients) received standard basic therapy. Inclusion in Reamberin regimens edematous form of acute pancreatitis in patients older than 60 years increases the effectiveness of treatment due to more rapid relief of symptoms of endogenous intoxication. The drug has a membrane stabilizing action, on the one hand, preventing the progression of the destruction of the pancreas and hence increase endogenous intoxication, the other - limiting structural disorders of the liver, normalizes its detoxification function. In addition, increasing the effectiveness of anticoagulant and fibrinolytic systems Reamberin corrects disturbances in the hemostatic system, contributing to the improvement of organ blood flow hepatopancreatoduodenal zone.

The purpose of this study was to evaluate the effectiveness of combined surgical and medical treatment of infective endocarditis in patients with congenital valvular heart disease when included in a regimen of the drug Reamberin. In this regard, the analysis of the effectiveness of a combination regimen of 74 patients with valvular congenital heart diseases complicated with infective endocarditis. Given the indications for surgical correction operative technique features and possible technical difficulties in carrying out such operations, due to the inflammatory changes and tissue destruction, and ways to overcome them. For the correction of metabolic disorders in the postoperative period, 47 patients (main group) was appointed Reamberin: once, intravenous drip 400 ml/day during the first 5 days after surgery. 27 patients (control group) was conducted infusion therapy depending on the severity of the condition according to the classical scheme. In addition to standard clinical and laboratory examination, to assess the effectiveness of Reamberin was investigated catalase activity of CPK in blood serum in the dynamics of observation (1, 3 and 5 days after surgery). It is revealed that surgical approach, used in complex treatment of patients with valvular congenital heart diseases, including reorganization of the cavities of the heart, increasing the frequency of joints and the use of reinforcing strips of synthetic material that prevents the cutting of sutures through the inflamed tissue has achieved good short-and long-term results. Infective endocarditis and destruction of the valvular annulus fibrosus the use of a frame of strips of polytetrafluoroethylene allows you to restore its integrity and to implant a mechanical prosthesis. The inclusion in the regimen of patients with infective endocarditis complicated by cardiac insufficiency in the early postoperative period the drug Reamberin improves the efficiency of treatment by a more rapid restoration of the normal metabolism of cardiomyocytes and accelerates elimination of signs of heart failure.

Objective: To study the efficacy of remaxol addition in the treatment scheme of alcohol withdrawal syndrome., Material and Methods: Eighty patients with alcohol dependence and physical symptoms of alcohol withdrawal syndrome were enrolled. All patients received basic therapy in accordance to the applicable standards of treatment. The patients were randomized to remaxol introduced intravenously 2 times a day (morning and afternoon) in dose of 400 ml for 7 days (n=40) and saline with 25%-magnesium sulfate (10 ml) and 4% potassium chloride (10 ml) (n=40)., Results: The effectiveness of the inclusion of remaxol was expressed in a more rapid relief of asthenic syndrome, reduction of phenomena such as tension, dysphoria, headache and impaired coordination of samples. Patients treated with remaxol demonstrated a trend towards a more rapid reduction of the affective (p=0.08) and behavioral components (p=0.09) of the syndrome of pathological craving for alcohol. Hepatoprotective and detoxification properties of the drug were confirmed by the significant decline in ALT and AST activity to the 20th day of treatment. Significant positive changes in lipid metabolism (HDL to the 7th day of treatment) and a normalizing effect on the processes of tissue respiration were shown as well. No adverse effects were noted., Conclusion: The data obtained allow to recommend the inclusion of remaxol in the complex treatment regimens of alcohol withdrawal syndrome to improve the treatment efficacy.

Unlabelled: PERPOSE OF RESEARCH: to evaluate the effectiveness of Remaxol in patients with pervasive peritonitis., Materials and Methods: assessed the effectiveness of a balanced infusion of the drug (Remaxol) in the treatment of 44 patients agedfrom 18 to 50 years. Patients were devided into 2 groups by the method of envelopes. All patients received a comprehensive differential therapy: 21 patient 1 group consisting of infusion therapy in the postoperative period received Remaxol at a dose of 800 mg/day for 7 days., Results: the comporative assessment of indicators of systemic hemodinamics, oxygen transport, asid base status, glucose, lactose and free radical oxydation. Patients on the first background was used Remaxol have experiensed a more rapid relief of metabolic disorders, endotoxemia and hepatic dysfunction compared with the indices of the 2 group patients. Noted earlier stabilization of rudicators of systemic hemodynamics and oxygen transport. This has reduced the duration of respiratory and vasopressor suppot, early start ofparenteral intreduction in case the power (p < 0.05)., Conclusions: this study shows that use of the drug for the purpose of relief Remaxol hepatic dysfunction and prevention of drug liver toxicity in conditions ofperitonitis, after 48 hours of operation, provides a positive dynamics and stabilization ofparameters of central hemodynamics, contributing to the abolition of vasopressor support, and contributes to the effective utilization of oxygen, while providing antioxidant effect.

The authors analyzed the antioxidant activity of reamberin and cytoflavin and evaluated their cardioprotective effect, by investigating lipid peroxidation and oxidative modification of plasma proteins, as well as the ultrastructure of newborn rat cardiomyocytes under chronic hemic hypoxia induced by sodium nitrite. Reamberin and cytoflavin can reduce the manifestations of mitochondrial dysfunction and the degree of cardiomyocyte damage in the neonatal rats due to the antioxidant and membrane-protective properties of the drugs. Succinic acid in combination with the metabolic components of the drugs significantly inhibits lipid peroxidation, by improving the structure of membranes and the mitochondrial function of cardiomyocytes.

56 patients at the age of 18-60 years with severe trauma were examined. Influence of the polyelectrolytic (Reamberin)solution on an acid-base state, osmolarity and electrolytic composition of plasma in the acute posttraumatic period was evaluated. It was found that patients, who was treated by isotonic sodium chloride solution and Ringer's solution, had metabolic acidosis and hyperchloremia. In contrast, in the reamberin group 82% of patients had lower concentrations of chloride and had nothing acid-base disturbances on the second day after trauma. Reamberin didn't influence on plasma osmolarity and the rate of metabolic alkalosis during the acute period of a trauma.

Maleic anhydride was reported illegally adulterated into starch to prepare traditional foods for decades in Taiwan. Maleic acid (MA), hydrolyzed from maleic anhydride, could cause kidney damages to animals. The potential health effects due to long-term MA exposures through food consumption have been of great concerns. Assessment of the dietary MA exposures could be very difficult and complicated. One of the alternatives is to analyze an MA-specific biomarker to assess the daily total MA intake. Therefore, this paper aimed to study the mercapturic acid of MA, 2-{[2-(acetylamino)-2-carboxyethyl]sulfanyl}butanedioic acid (MAMA), with our newly-developed isotope-dilution online solid-phase extraction liquid chromatography tandem mass spectrometry (ID-SPE-LC-MS/MS) method. MAMA was first synthesized, purified, and characterized with NMR to reveal two diastereomers and used for developing the analytical method. The method was validated to reveal excellent sensitivity with a LOD at 16.3ng/mL and a LOQ at 20.6ng/mL and used to analyze MAMA in urine samples collected from Sprague-Dawley rats treated with a single dose of 0mg/kg, 6mg/kg, and 60mg/kg (n=5) of MA through gavage. Our results show dose-dependent increases in urinary MAMA contents, and 70% MAMA was excreted within 12h with no gender differences (p>0.05). A half life of urinary MAMA was estimated at 6.8h for rat. The formation of urinary MAMA validates it as a chemically-specific biomarker for current MA exposure. Future study of MA metabolism in vivo will elucidate mechanisms of MAMA formation, and analysis of this marker in epidemiology studies could help to shed light on the causal effects of MA on human., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

The study describes the development of polylactide-tocopheryl polyethylene glycol 1000 succinate (PLA-TPGS)-based nanosystem as a carrier of crizotinib (CZT) to achieve superior anticancer efficacy in lung cancer therapy. We have demonstrated that block copolymer and hydrophobic drug is capable of self-assembling into a very stable nanocarrier, with suitable properties that allow their application for cancer drug delivery. Drug release study showed a sustained release pattern as a result of entrapment in the hydrophobic core of micelles. CZT/PT NP showed a noticeable cytotoxic effect in NCIH3122 lung cancer cells in a dose-dependent manner. Furthermore, morphological imaging and Live/Dead assay revealed a superior anticancer efficacy for nanoformulations. The polymeric nanoparticle showed a predominant presence in the cytoplasmic region of cell, indicating a typical endocytosis-mediated cellular uptake. The annexin V/PI staining-based apoptosis assay showed a remarkable ~40 % apoptosis (early and late apoptosis cells) comparing to only ~25 % apoptosis by free CZT. Taken together, Vitamin E TPGS-modified PLA nanoparticles would be a potential drug delivery system to increase the chemotherapeutic efficacy of CZT in lung cancer chemotherapy.

Background: The rates of stent failure after percutaneous coronary intervention have decreased since the introduction of the drug-eluting stent (DES). However, chronic kidney disease (CKD) and diabetes mellitus (DM) remain strong clinical predictors of poor prognosis despite DES implantation. Sarpogrelate, a selective serotonin (5-hydroxytryptamine (HT)2a [5-HT2A]) receptor antagonist, has antiproliferative effects, reducing neointimal hyperplasia and smooth muscle cell proliferation, as well as potent antiplatelet action, inhibiting 5-HT-induced platelet aggregation. However, efficacy and safety data for sarpogrelate in patients with CKD or DM are limited. We aim to determine whether sarpogrelate has beneficial effects in patients with CDK or DM treated with DES implantation., Methods/design: The SERENADE trial is a multicenter, open-label, prospective, randomized study that will test the superiority of triple anti-platelet therapy (TAT; aspirin, clopidogrel, and sarpogrelate) to conventional dual antiplatelet therapy (DAT; aspirin and clopidogrel) in preventing late lumen loss 9 months after the index procedure in patients with CKD or DM. A total of 220 patients diagnosed with coronary artery disease with DM or CKD will be randomized to the TAT or DAT groups (1:1 ratio) after DES implantation. The primary endpoint is late lumen loss at 9 months assessed by quantitative coronary angiography. Secondary efficacy endpoints are composites of major adverse cardiovascular events including cardiac death, nonfatal myocardial infarction, and target lesion revascularization. Secondary safety endpoints are major bleeding events and hepatic or renal impairment., Discussion: The SERENADE trial will provide insight on the efficacy of adjunctive therapy with sarpogrelate after DES implantation for patients with high-risk profiles such as CKD or DM., Trial Registration: National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov NCT02294643)., (Copyright © 2015. Published by Elsevier Inc.)

Purpose: To determine if sarpogrelate, a selective 5-HT2A receptor antagonist, is protective against light-induced retinopathy in BALB/c mice., Methods: BALB/c mice were dosed intraperitoneally with 5, 15, 30, 40, or 50 mg/kg sarpogrelate 48, 24, and 0 hours prior to bright light exposure (10,000 lux) as well as 24 and 48 hours after exposure. Additionally, a single injection regimen was evaluated by injecting mice with 50 mg/kg sarpogrelate once immediately prior to light exposure. To investigate the potential for additive effects of serotonin receptor agents, a combination therapy consisting of sarpogrelate (15 mg/kg) and 8-OH-DPAT (1 mg/kg) was evaluated with the 5-day treatment regimen. Neuroprotection was characterized by the preservation of retinal thickness and function, measured by spectral-domain optical coherence tomography (SD-OCT) and electroretinography (ERG), respectively., Results: Mice that were light damaged and injected with saline had significantly reduced outer retinal thickness, total retinal thickness, and ERG amplitudes compared with naïve mice. A 5-day administration of 15, 30, or 40 mg/kg of sarpogrelate was able to partially protect retinal morphology and full protection of retinal morphology was achieved with a 50 mg/kg dose. Both 15 and 30 mg/kg doses of sarpogrelate partially preserved retinal function measured by ERG, whereas 40 and 50 mg/kg doses fully preserved retinal function. Additionally, a single administration of 50 mg/kg sarpogrelate was able to fully preserve both retinal morphology and function. Administration of 15 mg/kg of sarpogrelate and 1 mg/kg of 8-OH-DPAT together demonstrated an additive effect and fully preserved retinal morphology., Conclusions: A 5- or 1-day treatment with 50 mg/kg sarpogrelate can completely protect the retina of BALB/c mice from light-induced retinopathy. Partial protection can be achieved with lower doses starting at 15 mg/kg and protection increases in a dose-dependent manner. Treatment with low doses of sarpogrelate and 8-OH-DPAT elicits an additive effect that results in full protection of retinal morphology.

Treatment with the complex preparation containing pantogam, succinic acid, and chitosan normalized the concentration of reduced glutathione and activities of glutathione peroxidase, glutathione reductase, and some NADPH-generating enzymes (glucose-6-phosphate dehydrogenase and NADPH-isocitrate dehydrogenase) in animals with experimental hypoxia/reperfusion of the brain. These results can be explained by suppression of free radical oxidation and normalization of the antioxidant system related to the neuroprotective, antihypoxic, and antioxidant properties of these substances, their involvement into the regulation of cell metabolism under pathological conditions accompanied by oxidative stress.

Objective: Although fresh frozen plasma (FFP) is one of the most commonly used hemostatic agents in clinical specialties today, there is little evidence available supporting its administration. Our present study observed the effects of a priming strategy without FFP during cardiopulmonary bypass (CPB) on postoperative coagulation and clinical recovery in pediatric patients, aiming to supply new evidence for evidence-based use of FFP., Method: Eighty pediatric patients with congenital heart disease undergoing cardiac surgery with CPB were randomized to receive either 10-20 ml/kg 4% succinylated gelatin (Gelofusine, GEL group, n = 40) or 1-2 units FFP (FFP group, n = 40) in the pump prime. Rapid-thromboelastography (r-TEG) and functional fibrinogen level were measured before skin incision and 15 minutes after heparin reversal. We recorded the volume of chest tube drainage, transfusion requirements and the dosage of pharmacological agents. The ventilation time, ICU length of stay and hospitalization time after surgery were also collected., Results: After heparin neutralization, there were significantly elevated levels of fibrinogen in the FFP group, which were manifested by r-TEG parameters MAf and FLEV. No significant differences were observed between the two groups in postoperative bleeding, transfusion requirements and the usage of pharmacological agents. Recovery time was also comparable between the two groups., Conclusion: In conclusion, prophylactic use of FFP in the priming solution does not provide clinical benefits as presumed. Artificial colloids, such as Gelofusine, can be used safely and effectively as a substitute for FFP in the pump prime. TEG is an effective assessment tool to evaluate postoperative coagulation function in pediatric patients., (© The Author(s) 2014.)

The effects of 3-oxypyridine and succinic acid derivatives (emoxipine, reamberin and mexidol) on affective disorders in rats with alloxan diabetes were studied. The efficiency of emoxipine, reamberin and mexidol was compared to alpha-lipoic acid, which is considered a "golden standard" in treatment of diabetic neuropathies. Emoxipine, reamberin and mexidol after seven administrations in single doses, that are equivalent to therapeutic range in humans, corrected the anxiety-depressive disorders in rats with alloxan diabetes. Unlike reamberin and alpha-lipoic acid, emoxipine and mexidol corrected the affective status concurrently with the decrease in hyperglycemia. At the same time, emoxipine outperformed mexidol in tranquilizing action (in maximal doses) but yielded mexidol in the antidepressant effect (in minimal doses).

1. Recently, we demonstrated that sarpogrelate is a potent and selective CYP2D6 inhibitor in vitro. Here, we evaluated the effect of sarpogrelate on the pharmacokinetics and pharmacodynamics of metoprolol in healthy subjects. 2. Nine healthy male subjects genotyped for CYP2D6*1/*1 or *1/*2 were included in an open-label, randomized, three treatment-period and crossover study. A single oral dose of metoprolol (100 mg) was administered with water (treatment A) and sarpogrelate (100 mg bid.; a total dose of 200 mg and treatment B), or after pretreatment of sarpogrelate for three days (100 mg tid.; treatment C). Plasma levels of metoprolol and α-hydroxymetoprolol were determined using a validated LC-MS/MS method. Changes in heart rate and blood pressure were monitored as pharmacodynamic responses to metoprolol. 3. Metoprolol was well tolerated in the three treatment groups. In treatment B and C groups, the AUCt of metoprolol increased by 53% (GMR, 1.53; 90% CI, 1.17-2.31) and by 51% (1.51; 1.17-2.31), respectively. Similar patterns were observed for the increase in Cmax of metoprolol by sarpogrelate. However, the pharmacodynamics of metoprolol did not differ significantly among the three treatment groups. 4. Greater systemic exposure to metoprolol after co-administration or pretreatment with sarpogrelate did not result in clinically relevant effects. Co-administration of both agents is well tolerated and can be employed without the need for dose adjustments.

Aims: In the critically ill patient, fluid loading is commonly done to stabilise hemodynamics and increase diuresis, whereas the absence of diuresis may predispose to harmful overloading. The goal of the current study was to evaluate the diuretic response and determinants thereof upon crystalloid and colloid fluid loading., Subjects and Methods: This is a substudy on 42 clinically hypovolemic, septic or non-septic patients without acute kidney injury, who were randomly assigned, after stratification for sepsis, to a 90-min fluid loading protocol with either 0.9% saline or a colloid solution (gelatin, hydroxyethyl starch 200/0.5 or albumin). Hemodynamics, biochemical parameters and diuresis were recorded. A response was defined by an increase in diuresis of >10% during fluid loading., Results: Diuresis increased more during saline than colloid infusion, together with a decline in colloid osmotic pressure (COP) of plasma and less increase in plasma volume and global hemodynamics with saline, at similar fluid balance. Nine patients (82%) receiving saline had a diuretic response, compared to 13 patients (42%) receiving colloids (P = 0.04), and the response was not predicted by underlying condition, global hemodynamics, volume of fluid infused and COP., Conclusion: In critically ill patients with clinical hypovolemia, diuresis increases more during saline than colloid fluid loading, only partly dependent of a fall in plasma COP.

Metaanalysis was applied to the published data on the randomized clinical trials of Remaxol in the treatment of various diseases associated with the liver injury: chronic hepatitis B and C, severe ethanol intoxication, drug-induced pathologies due to tuberculosis chemotherapy, leptospirosis, psoriasis, tumor polychemotherapy. The database included information on 2250 patients. The total number of the patients of the control group (n = 1099) were treated according to the routine schemes (active placebo) and that of the main group (n = 1151) were additionally treated with Remaxol. Combination of the frequency characteristics of the positive outcomes (% of elimination of the main clinical symptoms and complications) in the patients of the reference groups allowed to estimate the general clinical efficacy of Remaxol, that was equal to 1.75 by the outcome frequency characteristics. The odds ratio of the positive outcomes equaled 5.3 [1.8; 17.0] and the number of the patients needed to treat (NPNT) equaled 8 [6; 14]. Therefore, the infusion Remaxol hepatoprotector based on succinic acid was shown to have statistically and clinically significant therapeutic efficacy in pharmacologic correction of the liver pathologies of diverse genesis.

Design: A randomized prospective study., Patients and Methods: The study included 87 children aged from 5 to 18, ASA I-II. The patients were divided into two groups. We assessed the impact of reamberin 1.5% (succinate-containing infusion solution) on the level of metabolism and recovery after surgery in patients of main group (n = 44) and control group (n = 43) during different surgeries. All patients received general anaesthesia with sevoflurane, fentanyl, and rocuronium., Results: Reamberin 1.5% promotes to increase the level of basal metabolism in the early postoperative period, decreases the duration of awakening periods, improves recovery of motor activity and adequate breathing.

The abnormalities of myoelectrical activity of gastrointestinal tract were detected in 80 victims with severe combined trauma. There were observed a decrease of total electrical activity and dyscoordination of electrical activity of sections of gastrointestinal tract. An application of substrate antihypoxants should normalize the indices of myoelectrical activity of gastrointestinal tract. This approach allowed elimination of imbalance of total power between superposed (the stomach, the duodenum) and other sections of gastrointestinal tract. This would remove dyscoordination contraction of the jejunum and the ileum.

Immediate and long-term results of parenteral and oral administration of cytoflavin to patients with diabetic foot complicated by grade I and II trophic ulcers (Wagner classification) are considered with special reference to the assessment of reparative processes, normalization of the serum pro oxidant-antioxidant system, and improvement of clinical and instrumental bloodflow characteristics.