The functional indexes of RBCs and microcirculation in the traumatic brain injury with the action of 2-ethil-6-methil-3-hydroxypiridin succinate.

RESEARCH AIM: To study the RBCs functional and metabolic parameters and the microcirculatory brain structure at traumatic brain injury (TBI) under the action of 2-ethyl-6-methyl-3-hydroxypyridine succinate. METHODS: A closed TBI was modeled by the free fall of a load on the parietooccipital regions of head. We made studies of the influence of 2-ethil-6-methil-3-hydroxipiridin succinate on aggregation and electrophoretic mobility of RBCs, catalase activity, malonic dialdehyde concentration, adenosine triphosphate and 2.3-biphosphoglycerate (2.3 - BPG) concentrations in RBCs. The state of parenchyma and microcirculatory brain mainstream in post-traumatic period of TBI have been studied on micro-preparations. RESULTS: The use of 2-ethyl-6-methyl-3-hydroxypyridine succinate under conditions of head injury leads to a decrease in MDA concentration and in aggregation of RBCs, to an increase in the 2.3-BPG concentration and RBC electrophoretic mobility compared to the control (group value). The most pronounced changes under the action of 2-ethyl-6-methyl-3-hydroxypyridine succinate were observed 3-7 days after the TBI. Significant indicators of the restoration of the microvasculature and brain tissue provoked by the use of 2-ethyl-6-methyl-3-hydroxypyridine succinate of were evident from the 7th day unlike the control group, where the restoration of structural morphological parameters was observed only on the 12th day of the post-traumatic period. Fast recovery of blood flow under the action of 2-ethyl-6-methyl-3-hydroxypyridine succinate ensured effective restoration of neurons and glia in comparison with the control group. CONCLUSIONS: Early and long-term cytoprotective correction intensifies the oxygen transport function of the blood, prevents and / or reduces disorders of microvessels, neurons and glia in the post-traumatic period, thereby provides correction of hypoxic state and drives to the restoration of brain tissues homeostasis.

Discovery of JNJ-63576253: A Clinical Stage Androgen Receptor Antagonist for F877L Mutant and Wild-Type Castration-Resistant Prostate Cancer (mCRPC).

Persistent androgen receptor (AR) activation drives therapeutic resistance to second-generation AR pathway inhibitors and contributes to the progression of advanced prostate cancer. One resistance mechanism is point mutations in the ligand binding domain of AR that can transform antagonists into agonists. The AR F877L mutation, identified in patients treated with enzalutamide or apalutamide, confers resistance to both enzalutamide and apalutamide. Compound 4 (JNJ-pan-AR) was identified as a pan-AR antagonist with potent activity against wild-type and clinically relevant AR mutations including F877L. Metabolite identification studies revealed a latent bioactivation pathway associated with 4. Subsequent lead optimization of 4 led to amelioration of this pathway and nomination of 5 (JNJ-63576253) as a clinical stage, next-generation AR antagonist for the treatment of castration-resistant prostate cancer (CRPC).

A 2-year study of the impact of reduced nitrogen application combined with double inhibitors on soil nitrogen transformation and wheat productivity under drip irrigation.

BACKGROUND: Nitrification inhibitors (NIs) and urease inhibitors (UIs) can decrease the risk of nitrogen (N) loss and extend N uptake by plants. However, there are few case studies about reduced N application combined with double inhibitors (DIs, NI plus UI), especially under drip irrigation systems. A 2-year field experiment was therefore conducted to explore the effect of 80% N application rate combined with NI or DIs on soil N transformation, wheat productivity and N use efficiency (NUE) in a drip-irrigated field. The four treatments included a no-fertilizer control, 100% urea, 80% urea + NI (nitrapyrin) and 80% urea + DIs (nitrapyrin and N-(n-butyl) thiophosphorictriamide (NBPT)). RESULTS: Our results showed that the 80% urea + DIs treatment significantly increased the ratio of NH4 + to NO3 - and N content (urea-N, NH4 + -N and NO3 - -N) in soil at 0-20 cm depth (P < 0.05) at the heading stage and the filling stage of wheat in both 2013 and 2014, relative to the 100% urea treatment. A total of 80% urea + NI treatment decreased wheat N uptake and wheat productivity (plant biomass and yield) compared to 100% urea treatments (P < 0.05). However, application of 80% urea combined with DIs achieved equivalent wheat productivity with 100% urea treatment. Moreover, the greatest NUE (43.6%) was recorded with the application of DIs. CONCLUSIONS: Cutting the N application rate by 20% combined with NBPT and nitrapyrin could provide a sustainable fertilization strategy for wheat production under drip irrigation. © 2020 Society of Chemical Industry.

[The effect of Mexidol on cerebral mitochondriogenesis at a young age and during aging]. / Vliianie Meksidola na tserebral'nyi mitokhondriogenez v molodom vozraste i pri starenii.

AIM: To study the ability of mexidol to induce cerebral mitochondriogenesis in the brain of young and aging rats. MATERIAL AND METHODS: Expression level of marker proteins of cerebral mitochondriogenesis was evaluated during treatment with mexidol (20, 40, 100 mg/kg; 20 days; intraperitoneally) in the cerebral cortex of young (3 month) and aging (6, 9, 12, and 15 month) outbred male rats, using the Western blot analysis. RESULTS: It has been shown for the first time that the course injections of mexidol in doses of 40 and 100 mg/kg is accompanied by dose-dependent induction of the succinate receptor SUCNR1 and protein markers of mitochondrial biogenesis: transcription coactivator PGC-1α, transcription factors (NRF1, TFAM), catalytic subunits of respiratory enzymes (NDUV2, NDUV2,cytb, COX2) and ATP synthase (ATP5A) in the cerebral cortex of young and aging outbred male rats. Mexidol-dependent overexpression of subunits of mitochondrial enzymes and PGC-1α is observed only with the course of the drug. CONCLUSION: The results indicate the ability of mexidol to induce cerebral mitochondriogenesis and eliminate mitochondrial dysfunction in young and aging animals and, thus, exert an effect on one of the key pathogenetic links of the development of disorders in aging and neurodegenerative diseases.

Synthesis and Characterization of Fluorine-18-Labeled N-(4-Chloro-3-((fluoromethyl-d2)thio)phenyl)picolinamide for Imaging of mGluR4 in Brain.

We have synthesized and characterized [18F]-N-(4-chloro-3-((fluoromethyl-d2)thio)phenyl)-picolinamide ([18F]15) as a potential ligand for the positron emission tomography (PET) imaging of mGluR4 in the brain. Radioligand [18F]15 displays central nervous system drug-like properties, including mGluR4 affinity, potent mGluR4 PAM activity, and selectivity against other mGluRs, as well as sufficient metabolic stability. Radiosynthesis was carried out in two steps. The radiochemical yield of [18F]15 was 11.6 ± 2.9% (n = 7, decay corrected) with a purity of 99% and a molar activity of 84.1 ± 11.8 GBq/µmol. Ex vivo biodistribution studies showed reversible binding of [18F]15 in all investigated tissues including the brain, liver, heart, lungs, and kidneys. PET imaging studies in male Sprague Dawley rats showed that [18F]15 accumulates in the brain regions known to express mGluR4. Pretreatment with the unlabeled mGluR4 PAM compounds 13 (methylthio analogue) and 15 showed significant dose-dependent blocking effects. These results suggest that [18F]15 is a promising radioligand for PET imaging mGluR4 in the brain.

Neuroprotective and Antiamnestic Effects of a New Drug Emopag in Rats.

Emopag, a new drug, preventively administered in doses of 10 and 30 mg/kg/day over 4 days produced a pronounced neuroprotective effect in the model of brain ischemia caused by gravitational overload and reduced animal mortality from 17 to 0%. The preparation more effectively corrected neurological deficit than the reference drugs Mexidol (in considerably larger doses of 30 and 90 mg/kg/day) and antihypoxic drug amtizol (30 mg/kg/day). Moreover, Emopag exhibited considerable antiamnestic activity comparable to that of Mexidol (in 3-fold higher doses); in a dose of 30 mg/kg/day Emopag was more effective than Mexidol and amtizol in the same dose. Thus, Emopag showed marked neuroprotective and antiamnestic effects in the model of gravitational overload in rats.

Membranotropic and Antiradical Properties of 2-Nitroxysuccinate 3-Hydroxy-6-Methyl-2-Ethylpyridine.

We studied membranotropic properties of NO donor 2-nitroxysuccinate 3-hydroxy-6-methyl-2-ethylpyridine and its structural analog succinate 3-hydroxy-6-methyl-2-ethylpyridine (Mexidol). It was shown that the compounds under study are incorporated into modeled membranes and form long-living complexes with pyrene in the region of fatty acid tails of phospholipids. Luminol-amplified chemiluminescence analysis showed that both compounds exhibited antiradical activity and in a concentration of 0.1 mM reduced chemiluminescence intensity by more than 70%. 2-Nitroxysuccinate 3-hydroxy-6-methyl-2-ethylpyridine inhibited catalytic activity of monoamine oxidase A more efficiently than its structural analogue Mexidol.

Colon cleansing efficacy and safety with 1 L NER1006 versus sodium picosulfate with magnesium citrate: a randomized phase 3 trial.

BACKGROUND: Polyethylene glycol (PEG) bowel preparations are widely used for precolonoscopy bowel cleansing. This phase 3 trial assessed the efficacy, safety, and tolerability of the novel 1 L PEG-based NER1006 vs. sodium picosulfate plus magnesium citrate (SP + MC) in day-before dosing. METHODS: Patients requiring colonoscopy were randomized (1 : 1) to receive NER1006 or SP + MC. Cleansing was assessed on the Harefield Cleansing Scale (HCS) and Boston Bowel Preparation Scale (BBPS) using central readers. Two primary end points were assessed: overall colon cleansing success and high-quality cleansing of the right colon. Intention-to-treat (modified full analysis set [mFAS]) and per protocol (PP) analyses were performed. RESULTS: Of 515 patients, efficacy was analyzed in 501 (NER1006, n = 250; SP + MC, n = 251) and 379 patients (NER1006, n = 172; SP + MC, n = 207) in the mFAS and PP analyses, respectively. Non-inferiority of NER1006 vs. SP + MC was established in the mFAS for both overall cleansing (62.0 % vs. 53.8 %; P = 0.04) and high-quality cleansing in the right colon (4.4 % vs. 1.2 %; P = 0.03). Superiority of NER1006 was demonstrated using HCS in the PP set for overall cleansing success (68.0 % vs. 57.5 %; P = 0.02) and right colon high-quality cleansing (5.2 % vs. 1.0 %; P = 0.02) and using BBPS in the mFAS for overall cleansing success (58.4 % vs. 45.8 %; P = 0.003) and right colon high-quality cleansing (4.0 % vs. 0.8 %; P = 0.02). Mean segmental scores for 4/5 segments were higher with NER1006 (P ≤ 0.04). Both treatments were well tolerated, with more mild adverse events for NER1006 (17.0 % vs. 10.0 %; P = 0.03). CONCLUSIONS: Colon cleansing with NER1006 vs. SP + MC was non-inferior (mFAS) and superior (PP), with acceptable safety.European Clinical Trials Database (EudraCT)2014-002186-30TRIAL REGISTRATION: Multicenter, randomized, parallel group, phase 3 study 2014-002186-30 at https://eudract.ema.europa.eu/.

[Effect of mexidol on physical working capacity and level of lactate in the blood of rats in conditions of light deprivation]. / Vliianie meksidola na fizicheskuiu rabotosposobnost' i uroven' laktata v krovi krys v usloviiakh svetovykh desinkhronozov.

AIM: To study an effect of mexidol on the performance of rats after light or dark deprivations in the swimming test with a load and to evaluate the state of glycolytic processes under these conditions. MATERIAL AND METHODS: The experiment was carried out in the spring on 70 Wistar male rats. Three groups (30 animals) were in natural light conditions. One of them was not affected. The other two groups were subjected to exercise and 30 minutes before it either saline or mexidol was administered intramuscularly. Four other groups (40 animals) for 10 days were under conditions of dark or light deprivation prior to the presentation of physical activity and received either saline or mexidol before the test after deprivation was canceled. A forced swimming test with an additional load, which was presented to animals every day at 10-11 am for five days in a row, was used as a model of physical activity. The level of lactate was determined by colorimetric method. RESULTS AND CONCLUSION: Mexidol increased the performance of rats in the swimming test, both under natural lighting conditions and with light desynchronization, contributed to the formation of cross adaptation to physical activity under natural lighting conditions and prolonged this state under conditions of light deprivation, did not change the content of lactate in the blood of rats after exercise in natural lighting conditions and dark deprivation and prevented its rise after light deprivation.

Antioxidant Properties of a Pharmaceutical Substance Hypocard, a Potential Drug for Ischemic Disease.

Antioxidant activity of a pharmaceutical substance hypocard was compared with activity of nitromalic acid and well-known agents nicorandil and Mexidol. The ability of these substances to inhibit spontaneous and oxidant-induced LPO process in rat brain homogenate was analyzed. The mechanisms of these effects were studied. The antioxidant properties of hypocard manifested in the inhibition of Fe(II)-induced LPO were significantly more pronounced in comparison with Mexidol and nicorandil.

Pharmaceutical salts of emoxypine with dicarboxylic acids.

New salt forms of the antioxidant drug emoxypine (EMX, 2-ethyl-6-methylpyridin-3-ol) with pharmaceutically acceptable maleic (Mlt), malonic (Mln) and adipic (Adp) acids were obtained {emoxypinium maleate, C8H12NO+·C4H3O4-, [EMX+Mlt], emoxypinium malonate, C8H12NO+·C3H3O4-, [EMX+Mln], and emoxypinium adipate, C8H12NO+·C6H9O4-, [EMX+Adp]} and their crystal structures determined. The molecular packing in the three EMX salts was studied by means of solid-state density functional theory (DFT), followed by QTAIMC (quantum theory of atoms in molecules and crystals) analysis. It was found that the major contribution to the packing energy comes from pyridine-carboxylate and hydroxy-carboxylate heterosynthons forming infinite one-dimensional ribbons, with [EMX+Adp] additionally stabilized by hydrogen-bonded C(9) chains of Adp- ions. The melting processes of the [EMX+Mlt] (1:1), [EMX+Mln] (1:1) and [EMX+Adp] (1:1) salts were studied and the fusion enthalpy was found to increase with the increase of the calculated lattice energy. The dissolution process of the EMX salts in buffer (pH 7.4) was also studied. It was found that the formation of binary crystals of EMX with dicarboxylic acids increases the EMX solubility by more than 30 times compared to its pure form.

Evaluation of the Possibility of Correction of Doxorubicin-Induced Chronic Heart Failure in the Experiment with 3-Hydroxypyridine Acetylcysteinate and 3-Hydroxypyridine Succinate.

The possibility of correction of morphological changes in the myocardium and biochemical parameters of the blood with 3-hydroxypyridine acetylcysteinate in a dose of 25 mg/kg was studied in the model of doxorubicin-induced chronic heart failure in rats. It was found that 3-hydroxypyridine acetylcysteinate in a dose of 25 mg/kg produced less pronounced cardio-protective effect in experimental chronic heart failure than 3-hydroxypyridine succinate.

[The study of the membrane-protective potential of the combination of 2-ethyl-6-methyl-3-hydroxypyridine-succinate and citicoline]. / Issledovanie membranoprotektivnogo potentsiala kombinatsii preparatov 2-étil-6-metil-3-oksipiridina-suktsinata i tsitikolina.

AIM: To assess the changes in the composition of plasma phospholipids in patients with chronic cerebrovascular disease treated with neuroprotectors 2-ethyl-6-methyl-3-hydroxypyridine succinate (neurox) and citicoline (neipilept), the natural metabolites involved in biochemical processes in the body, and their composition. MATERIAL AND METHODS: The study included 40 patients, 18 men and 22 women, aged from 54 to 72 years, with chronic cerebrovascular disease at the decompensation stage complicated with the hypertensive crisis and/or arrhythmia. RESULTS AND CONCLUSION: During extraction of phospholipids from blood cells, a significant decrease in the amount of total lipids was found to the end of treatment of patients who received neurox or neipilept or their combination. The study of quantitative composition of phospholipids showed no significant changes in patients treated with neurox, while the use of citicoline or combination of citicoline with 2-ethyl-6-methyl-3-hydroxypyridine succinate resulted in the increase of their total mass. There were no significant changes in the qualitative composition of phospholipid classes in blood plasma in patients treated with neurox. In patients treated with neipilept or with the combination of citicoline with 2-ethyl-6-methyl-3-hydroxypyridine succinate, plasma phosphatidylcholine was significantly increased. No significant changes in the content of phosphatidylinositol, phosphatidylserine and sphingomyelin were observed.

bis-(p-hydroxyphenyl)-pyridyl-2-methane (BHPM)-the active metabolite of the laxatives bisacodyl and sodium picosulfate-enhances contractility and secretion in human intestine in vitro.

BACKGROUND: Stimulant laxatives are widely used to treat constipation. We investigated in human small and large intestinal preparations the effects of bis-(p-hydroxyphenyl)-pyridyl-2-methane (BHPM), the active metabolite of the laxatives bisacodyl and sodium picosulfate on smooth muscle tone and epithelial secretion. METHODS: Circular and longitudinal muscle tone of small or large intestinal preparations were recorded with isometric force transducers. Epithelial ion flux (ISC ) and tissue resistance was measured with Ussing chamber technique after apical and basolateral BHPM application to large intestinal mucosa/submucosa preparations. Studies were performed in macroscopically normal specimens from 79 patients. KEY RESULTS: BHPM concentration-dependently (0.5-5 µM) increased the tone of circular and longitudinal muscle from small to large intestine. The effect was strongest in large intestinal longitudinal muscle and smallest in small intestinal circular muscle. Increase in muscle tone was prevented by the L-type Ca++ channel blocker nifedipine but insensitive to the nerve blocker tetrodotoxin. Apical or basolateral BHPM concentration-dependently decreased or increased ISC, respectively. The KCa 1.1 (BK) channel blocker iberiotoxin reversed apical ISC decrease whereas tetrodotoxin reversed basolateral ISC increase. BHPM had no effect on tissue resistance or nerve-mediated secretory or muscle response with one exception: at the highest concentration basolateral BHPM reduced nerve-mediated secretion. CONCLUSIONS AND INTERFERENCES: BHPM enhanced mucosal secretion and muscle contractility. Results suggested that the laxative effect of BHPM was a consequence of the increase in muscle tone as well as an increased K+ secretion when acting luminally and a nerve-driven Cl- and HCO3- secretion once acting basolaterally after absorption.

Efficacy and Safety of Sodium Picosulfate/Magnesium Citrate for Bowel Preparation in a Physically Disabled Outpatient Population: A Randomized, Endoscopist-Blinded Comparison With Ascorbic Acid-Enriched Polyethylene Glycol Solution Plus Bisacodyl (The PICO-MOVI Study).

BACKGROUND: Because of its volume, adequate bowel preparation remains problematic in physically unfit patients. OBJECTIVE: This study aimed to compare a small-volume sodium picosulfate/magnesium citrate preparation with a 2-L ascorbic acid-enriched polyethylene glycol solution plus bisacodyl. DESIGN: This study has a noninferiority design, assuming that ascorbic acid-enriched polyethylene glycol solution plus bisacodyl is 70% efficacious in achieving an Ottawa score ≤7 and accepting a difference in success rate of <15% with a target enrollment of 146 patients per group. SETTING: This study was conducted in an outpatient department. PATIENTS: Patients referred for diagnostic colonoscopy were randomly assigned. Key exclusion criteria were severe kidney disease, ASA class ≥III, and hospital admission. INTERVENTION: Patients were randomly assigned to receive sodium picosulfate/magnesium citrate or ascorbic acid-enriched polyethylene glycol solution plus bisacodyl according to a split-dose regimen. Patients in the sodium picosulfate/magnesium citrate group received advice on the recommended 4-L fluid intake. Patients in the ascorbic acid-enriched polyethylene glycol solution plus bisacodyl group received 2 bisacodyl tablets 2 days before and advice on the additionally recommended 2-L fluid intake. MAIN OUTCOME MEASURES: To assess bowel-cleansing adequacy, the Ottawa, Aronchick, and Boston scores were used. Colonoscopy quality measures were obtained. Safety was assessed for a 30-day follow-up period. RESULTS: Overall, 341 patients (169 men, mean age 57.0 years; BMI 26.2 kg/m) were included. Comorbidities were present in 76.2% of patients, and 75.4% of patients used medication. An adequate Ottawa score was obtained in 81.4% and 75.8% of patients receiving ascorbic acid-enriched polyethylene glycol solution plus bisacodyl and sodium picosulfate/magnesium citrate (difference of 5.6% (95% CI, -3.5 to -14.6; p = 0.023)), showing noninferiority of the sodium picosulfate/magnesium citrate therapy. Ottawa segmental scores were lower for sodium picosulfate/magnesium citrate in the right and transverse colon. In both groups, successful ileocecal intubation was achieved in 95%. No medication-related adverse events were reported. LIMITATIONS: These results in a physically disabled ambulant population cannot be extrapolated to immobile, hospitalized patients. CONCLUSIONS: Sodium picosulfate/magnesium citrate proved to be noninferior to ascorbic acid-enriched polyethylene glycol solution plus bisacodyl in efficacy and safety. Timing of the colonoscopy and addition of bisacodyl to sodium picosulfate/magnesium citrate warrants further consideration. See Video Abstract at http://links.lww.com/DCR/A461.

The Role of Succinate in Regulation of Immediate HIF-1α Expression in Hypoxia.

Hypoxia-induced immediate expression of transcription factor HIF-1α in the brain cortex is regulated by succinate produced in both the tricarbonic acid cycle and GABA shunt reactions and is induced by succinate-containing drugs. These facts prove the existence of succinate-dependent signalling regulation involved in immediate and delayed molecular adaptation and increased body resistance to oxygen deficiency, where succinate acts as a signal molecule. The intensity of this process differs in animals with low and high resistance to hypoxia.

[A modern concept of antihypoxic and antioxidant effects of mexidol]. / Sovremennye predstavleniia ob antigipoksicheskom i antioksidantnom éffektakh meksidola.

The review article presents a modern concept of the mechanism of antioxidant and antihypoxic action of the original drug mexidol (2-ethyl-6-methyl-3-hydroxypyridine succinate). The direct antioxidant activity of mexidol has been described, which consists in the ability of the drug to inactivate free radicals and increase the activity of the antioxidant enzymes glutathione peroxidase and superoxide dismutase in vitro. The results of the indirect antioxidant activity of mexidol, manifested in the increased expression under the ischemia of the transcription factor Nrf2, responsible for the cell resistance to oxidative stress are presented. The antihypoxic action of mexidol due to the presence of succinic acid in its molecule, which on the one hand supports the work of the Krebs cycle succinate oxidase under oxygen deficiency conditions, and on the other hand, binds to its specific receptors (GPR91), and starts a cascade of biochemical reactions that increases the body's resistance to lack of oxygen is discussed. The results of preclinical and clinical studies confirming the antioxidant and antihypoxic effects of mexidol are summarized.

Homo- and heteroleptic Pt(II) complexes of ONN donor hydrazone and 4-picoline: A synthetic, structural and detailed mechanistic anticancer investigation.

Two series of homoleptic Pt(II)(hydrazone)Cl (C1a-C5a) and heteroleptic Pt(II)(hydrazone)(4-picoline). BF4 (C1b-C5b) complexes were prepared and characterized by 1H, 13C, 19F NMR and HR ESI-MS. Structure of C2b was confirmed by single crystal X-ray analysis. These complexes were studied for their in vitro anticancer activities in human multiple cancer cells including breast (MCF-7), liver (HepG2), lung (H460), colon (HCT116) and cervical (Hela) cancers. C1a-C5a and C1b-C5b showed considerable anticancer effect. The overall anticancer effect of all these complexes was higher in liver (HepG2) and lung (H460) cancer cell lines and the effect of C2b and C3b was observed to be the highest among these 10 complexes. Therefore, we selected C2b and C3b to study their in vitro anticancer mechanism in HepG2 and H460 cancer cells. C2b and C3b changed cancer cell morphology and inhibited cell migration. The anticancer mechanistic studies demonstrated that C2b and C3b induced cell apoptosis, as evidenced by DAPI and AO/EB staining and flow cytometry analyses. Moreover, qRT-PCR and western blotting analysis showed that H460 and HepG2 cells treated with C2b and C3b significantly increased the expression of p53, p63, p21, p15, Bax and decreased Bcl-2 and c-Myc levels. The DNA binding property of these complexes was investigated by gel electrophoresis using pBR322 plasmid DNA. Taken together, the results obtained from the present study demonstrated the potentials of this new class of Pt(II) complexes in reduction of cell viability, suppression of cell migration and acceleration of apoptosis in different cancer cells.

[Disorders in structural-functional properties of erythrocytes in experimental acute destructive pancreatitis of alcohol etiology and their correction]. / Narushenie strukturno-funktsional'nykh svoistv éritrotsitov pri éksperimental'nom ostrom destruktivnom pankreatite alkogol'noi étiologii i ikh korrektsiia.

The effects of various combinations of pharmacological agents on parameters characterizing red blood cell (RBC) membrane proteins and lipids have been investigated in RBC isolated from Wistar male rats with acute destructive pancreatitis induced under conditions of forced alcoholization for 60 days. Administration of a combination of Hepon, Hypoxenum, and Phosphogliv normalized 22.5% of parameters altered change during development of acute destructive pancreatitis under conditions of chronic alcoholization of parameters, corrected towards normal values 42.5% of parameters (35% of parameters remained unchanged). Administration of Glutoxim, Mexidol and Heptral, was more effective: this combination normalized 50.0% of parameters studied, corrected towards normal values 37.5% of parameters, leaving unchanged only 12.5% of parameters studied.

Comparison of the Pharmacological Effects of Dimeric Dipeptide Nerve Growth Factor Mimetic GK-2 and Mexidol on the Model of Ischemic Stroke in Rats.

We compared the effects of GK-2 (dimeric dipeptide mimetic of nerve growth factor) and Mexidol (standard preparation for the therapy of stroke) on rat model of transient occlusion of the middle cerebral artery. GK-2 and Mexidol were administered intraperitoneally in the most active doses (1 and 100 mg/kg, respectively) 6 h after surgery and then once a day for 6 days. The preparations reduced the volume of cerebral infarction (by 60 and 30%, respectively). At the same time, GK-2 had a pronounced and statistically more reliable effect in a dose that is lower by two orders of magnitude. In addition, GK-2 significantly reduced the neurological deficit in the limb placement test, while Mexidol was ineffective in this test.