[Observational study of the efficacy and safety of the drug Ampasse in patients with moderate cognitive impairment in chronic cerebral ischemia]. / Nablyudatel'noe issledovanie effektivnosti i bezopasnosti primeneniya preparata Ampasse u patsientov s umerennymi kognitivnymi narusheniyami pri khronicheskoi ishemii golovnogo mozga.

OBJECTIVE: The study of the efficacy and safety of drug Ampasse in the treatment of mild cognitive impairment syndrome (MCI) in patients with chronic cerebral ischemia (CCI) and as an adjuvant therapy in the treatment of chronic pain syndromes of various origins. MATERIAL AND METHODS: 50 patients with an average age of 67±7.4 years with MCI syndrome against the background of CCI, suffering from chronic pain syndromes of various origins, received the drug Ampasse at a dose of 25 mg per day intravenously by bolus for 15 days. At the screening visit, day 15 of therapy, day 30, and day 180 of the observation period, cognitive functions, emotional sphere, severity of pain syndrome, sleep quality, and quality of life were assessed. RESULTS: In 95% of patients during therapy, an improvement in cognitive functions was noted (increase by 2 points on scales MoCA and MMSE, p<0.05). The maximum severity of cognitive improvement was achieved by the 30th day of observation. By the 180th day of observation, 5% of patients had returned to their original cognitive status, which is probably due to the need for a repeated course of therapy to maintain the clinical effect. The antiamnestic effect of Ampasse was also manifested in patients with a multifunctional amnestic phenotype of MCI, which may indicate a comorbidity with a neurodegenerative disease. A total of 84% of patients experienced a decrease in pain intensity during treatment (decrease by 2.3 points on VAS, decrease in consumption of analgesics by 1.5 tablets per day, p<0.05). This effect persisted throughout the observation period and was associated with improved sleep quality. In the course of treatment, no cases of anxiety or depression were detected. All patients showed an improvement in their quality of life according to the scale SF-36. The use of Ampasse showed a good level of tolerability and safety. CONCLUSION: The use of Ampasse is effective and safe in the treatment of MCI in CCI and helps to reduce the clinical manifestations of pain syndromes of various origins. The mechanism of the analgesic action of Ampasse, as well as the need for and optimal timing of repeated courses of therapy, require further study.

[The effect of the start date of cognitive rehabilitation after ischemic stroke on the level of recovery]. / Vliyanie sroka nachala kognitivnoi reabilitatsii posle perenesennogo ishemicheskogo insul'ta na uroven' vosstanovleniya.

OBJECTIVE: The dependence of result of cognitive training in patients who have suffered an ischemic stroke (IS) on the timing of their onset continues to be discussed. The aim was to study the results of cognitive rehabilitation of patients after IS during various periods after it. MATERIAL AND METHODS: 140 patients were examined during complex rehabilitation in terms up to 1, 2-3, 4-6 and 7-12 months after IS, 78 of them received drug support (DS) of rehabilitation with intravenous injections of ampasse. The Montreal Cognitive Assessment (MoCA) and Hospital Anxiety and Depression Scale (HADS) were used to monitor the effectiveness of rehabilitation. RESULTS: In all subgroups, there was a statistically significant increase in the MoCA score after the course, but number of people with an increase in the score by 1 or more points was highest among those who started the course 3 or more months after the development of IS (p=0.015). Among those who received DS, an increase in the MoCA was noted in 87.2%, in those who did not receive it - 38.7% (p<0.001). There was no statistically significant increase in the severity of anxiety and depression after the course of treatment in any of the subgroups. CONCLUSION: The used approach of a combination of cognitive, physical rehabilitation and DS proved to be justified for achieving results during a two-week course of inpatient rehabilitation of patients both in the early and late recovery period after IS.

Oligomerization of ß-Like DNA Polymerases in the Presence of Fe2+ Ions.

This work presents data on the relationship between the oligomeric state and catalytic activity of ß-like DNA polymerases isolated from three cancer cell lines upon replacement of magnesium ions with iron. It was shown that the suppression of the catalytic activity of ß-like DNA polymerases in the presence of divalent iron ions is related to enzyme oligomerization that can be responsible for the suppression of the magnetic isotope effect.

[Ampakines - a promising approach to neuroprotection]. / Ampakiny ­ novyi podkhod k neiroprotektsii.

Increased interest in glutamatergic neurotransmission emerged in the second half of the twentieth century. Later, the role of glutamate neurotransmission in learning and memory processes became clear. AMPA receptors (AMPR) and NMDA receptors (NMDAR) turned out to be important links in the mechanism of long-term potentiation (LTP) involved in memory processes, which was expressed in an increase in the excitatory postsynaptic potential in response to repeated stimuli. The data obtained in recent decades indicate that AMPR is the main regulators of synaptic plasticity, learning and memory. In clinical terms, the greatest interest is not the formation of memory traces in various parts of the brain, but its restoration in various pathological processes, including reactivation of connections between neurons activated by learning in various areas of the brain. AMPAR synaptic plasticity disorder has been detected in several neurodegenerative diseases accompanied by cognitive disorders. Ampakines, a heterogeneous class of numerous small molecules that bind to the allosteric site on the AMPAR receptor, which slows down the kinetics of AMPAR deactivation, enhances excitatory synaptic current and enhances LTP, have become increasingly attracting the attention of researchers.

Radiation-Chemical Biotechnology for Producing Ultrashort (50-100n) Single-Chain Polydeoxyribonucleotides with Anticancer Activity.

The fundamental possibility of obtaining ultrashort (50n-100n) single-stranded polydeoxyribonucleotides by the method of radiation-chemical destruction of total yeast DNA was established and their anticancer activity was shown.

L, D-Polydeoxyribonucleotides to provide an essential inhibitory effect on DNA polymerase ß of human myeloid leukemia HL60 cells.

The inhibitory effect of D and L-polynucleotides of a given length (40-50n) on the catalytic activity of DNA polymerase ß isolated from chromatin cells of acute myeloid leukemia HL-60 was evaluated. The synthesized L enantiomer was found to have a higher inhibitory activity than the synthesized and isolated D enantiomers of polynucleotides. The work also proposes a biophysical model that describes this effect.

[A randomized, double-blind, placebo-controlled study of the efficacy and safety of ampasse in the treatment of chronic cerebral ischemia]. / Randomizirovannoe dvoinoe slepoe platsebo-kontroliruemoe issledovanie éffektivnosti i bezopasnosti preparata ampasse v terapii khronicheskoi ishemii mozga.

AIM: To study the efficacy and safety of ampasse in the treatment of chronic cerebral ischemia. MATERIAL AND METHODS: A randomized, double-blind, placebo-controlled study of the efficacy and safety of the 5-hydroxy-3-carboxypyridine-L-glutamine acid monocalcium salt (ampasse) was performed in 80 patients, aged from 50 to 75 years, with chronic cerebrovascular accident due to arterial hypertension and/or atherosclerosis of the main arteries of the head. The drug was used in daily doses of 5, 10, or 25 mg intravenously once a day for 15 days. Sodium chloride 0.9% was used as a placebo. RESULTS AND CONCLUSION: It has been established that ampasse improves the state of patients with chronic cerebral ischemia in relation to depression, sleep quality and cognitive functions.

Protective Properties of Lanthanum Nitrate against Pathogens with Various Morphological and Functional Properties.

Dose-dependent protective effects of lanthanum nitrate solution and gel were shown on the model of experimental infection caused by a virulent strain of Shigella flexneri 2a or opportunistic bacteria Klebsiella pneumoniae in outbred and DBA mice.

Drift mechanism of the metal nanowires formation in liquid helium.

It is shown theoretically that the mechanism of the rapid coagulation of metal nanospheres into a nanowire in a quantum vortex proposed by E. B. Gordon et al. (Low Temp. Phys., 2010, 36, 590) could not be realized, due to the enormous heat release expelling the nanospheres from the vortex. Also, Gordon's hypothesis on nanowire formation in quantum vortices contradicts the observations that nanowires form above the λ-point (where no quantum vortices exist) and on superfluid helium's surface (parallel to it), which is always perpendicular to the quantum vortices. The nanowire formation process in bulk and dropwise liquid helium is described as a special case of aggregation controlled by diffusion in an external electric field. The nanosphere charging occurs due to the thermoelectric emission from their overheating and also laser ablation. The charged nanospheres attract neutral ones to minimize the electrostatic energy and are also attracted to elevations (field concentrators) on the conductive surfaces surrounding the experimental volume. Both processes lead to nanowire formation and drift prevails over diffusion in both cases. The described mechanism leads to the formation of self-similar anisometric structures in agreement with experimental data.

[Gelation in Low Concentrated Solutions of Cholesterol and Ergosterol].

The molecular dynamics method has been applied to investigate the conformational behavior of biologically important chiral molecules of cholesterol and ergosterol. The formation of strings in the solution of cholesterol in methanol and the lack of strings in solutions of ergosterol in methanol has been experimentally detected. It was shown that the intermolecular dynamics in the molecule has a significant impact on the potential of structure formation. We proposed alternative explanation of the functional significance of cholesterol, apparently associated with the formation of interconnect structures outside the membrane as the biological feasibility of finding ergosterol in non-switched cells of fungi and cholesterol in the switching cells of macroorganisms.

Supercoiling as a Physical Process Providing Formation of Macroscopic Anisometric Supramolecular Structures.

Solutions of chiral and achiral trifluoroacetyl amino alcohols (TFAAA) contain anisometric structures with a diameter <1 nm and length ~7 nm. In homochiral solutions and xerogels, chiral TFAAA form strings with a diameter of ~30-100 nm and length more than ~1 µ, and achiral TFAAA condensate into isometric granule with diameter of ~1 µ. We conclude that molecular chirality determines helicity of strings within tens of nanometers or more. Stabilization of supramolecular structure of strings is presumably achieved via their supercoiling.

["Microbiological aging" by Mechnikov. How to interpret these ideas today?].

I.I. Mechnikov's hypothesis that the key to prolongation of life lies in the introduction of useful microflora to the gut was not proved. Any microflora needs nutrition and perceives the human body only as a nutrient substrate. Destruction of the basement membranes, that delimit the contacting with aggressive microbiological environment epithelium from the deeper parts of the body, can lead to chronic inflammatory diseases and aging of the skin as a consequence of the invasion of microorganisms. At the ultrastructural level it has been shown by the example of prostatitis and skin aging changes. Coupled with the penetration of germs flow of immune cells may cause autoimmune reactions due to abrupt changes in the molecular design of the intermembrane transport. Thus, the physiological process of macroorganism aging can be viewed as a consequence of its microbiological destruction.

[Experimental observation of synergetic regular change of chirality sign in the hierarchy of biomimetic structures].

Having investigated chiroptical characteristics of homochiral solutions of biomimetics the rule of changing a chirality sign in spontaneous formation of supramolecular helical structures was experimentally substantiated. This self-organization presents evidence of a fundamental synergetic law of changing the chirality sign during the transition to a higher hierarchical level, being of common for modular prebiotic homochiral systems and basic molecular biological systems.

Metric similarity of dynamic commutation processes in situ and in vitro.

The dynamics of string growth was studied in model homochiral solutions of biomimetics, trifluoroacetylated amino alcohols (TFAAA) in heptane, water, and inverted heptane-water emulsion. In heptane and water, a thick (~1 µ in diameter) string had a crown of thin strings on its growing terminal and these thin strings effectively adsorbed dissolved TFAAA. In emulsion, the strings grew inside the water droplets, in which this TFAAA cannot be solved, presumably due to transport of TFAAA molecules from heptane into water in the surface layer surrounding the string. Applications of these phenomena to in vivo cell commutation were discussed.

Effects of physicochemical forms of phenazepam and Panavir on their action at ultra-low doses.

A concept of physicochemical forms of biologically active substances introduced in investigation of the action mechanism of ultra-low doses allows qualitative explanation of the main effects of ultra-low doses, chemical diversity of biologically active substances, and physical boundaries for these effects. Phenazepam was shown to possess activity in ultra-low doses only in disperse state, in the form of nanoparticles with a diameter <100-300 nm; these nanoparticles appear as micelles of surface active substances and solvated. Panavir possesses pharmacological activity in ultra-low doses and appears as nanoparticles with a diameter of 200-300 nm, which have uncompensated negative surface charge and polymer nature.

Role of prostatic epithelium basement membrane incompetence in the pathogenesis of chronic prostatitis.

Prostatic inflammation is associated with infections penetrating through the urethra. This inflammation is treated by long courses of wide-spectrum antibiotics. However, the most frequent cause of prostatitis is Escherichia coli and other enteric flora. Electron microscopy of biopsy specimens from the prostate detected gaps in the prostatic epithelium basement membrane, their size explaining the penetration of enteric flora into the prostate. These data suggest another view on the pathogenesis of prostatitis and approaches to improvement of therapy for this disease.

Physicochemical simulation of cell-cell commutation.

Strings, anisometric structures with length-diameter ratio of 10(1)-10(5) are formed in some homochiral solutions at a concentration of 10(-3)-10(-2) M. We studied macroscopic properties of strings (strength, charge at the ends, etc.) and showed that these strings can provide a power commutation of cells. The strength and electrostatic driving force of the strings are sufficient to transport cells with a velocity of app. 1 cm/sec. The formation of strings is a mechanism of directional and error-resistant information exchange and for intercellular distances it is faster and more efficient by substance utilization than the diffusion mechanism. This suggests that strings or similar objects, including cytonemes, play an important role in various aspects of cell-cell commutation.

Biological fluids as chiral anisometric media.

Molecules of dissolved substance in many homochiral solutions are arranged in linear associations forming chiral strings (with length to diameter proportion of 10(1)-10(5)), which leads to solidification of the solution into anisometric gel. This paper describes the formation of the string system in aqueous solution of amino acid phenylalanine, formation of individual strings, weaving of thin strings into thick ones, successive alteration of the solution chirality sign with transition to new levels of the association organization. It seems that biological media are anisometric fluids containing chiral molecular associations and strings, or anisometric gels.

[The influence of calcium N-(5-hydroxynicotinoyl)-L-glutamate on reproductive function, prenatal and postnatal development of rats].

The safety of a new nootrope and neuroprotector--calcium N-(5-hydroxynicotinoyl)-L-glutamate (ampasse)--has been evaluated. It is shown that ampasse at a dose of 6.7 mg/kg (10 times the maximum therapeutic dose for humans) did not affect the reproductive function in experimental animals and did not produced any embryotoxic and teratogenic effects.

Superspiralization of chiral strings.

A phenomenon of superspiralization was revealed in homochiral solutions of biomimetics with strings lengths from 10(2) nm to 10(2) µ and longer: strings of greater size spontaneously formed in solution are twined of the smaller strings, which also have a helical structure. The chiral pitch depends on the conditions of formation of a particular string and can vary by several times in different strings of the same specimen.