[Pavel I. Emdin: Biography without blank spots]. / Pavel Iosifovich Emdin Biografiya neirokhirurga bez belykh pyaten.

The authors present the career of Professor Pavel I. Emdin as one of the pioneers of Russian neurosurgery. Archive documents, biography and scientific articles are analyzed. The merit of Pavel I. Emdin as an organizer of national health care is «armament¼ of neuropathologists with surgical methods of treatment. He created the first in Russia Department of Nervous Diseases with clinics of neurology and neurosurgery at the Don University in Rostov-on-Don. He created the Rostov school of neurosurgeons, whose representatives continued the work of their teacher in various regions of the Soviet Union. Professor Pavel I. Emdin is a bright figure in the galaxy of Russian and Soviet neuropathologists and neurosurgeons with outstanding organizational and professional qualities regarding development of neurosurgery in our country.

False Aneurysm of the Proximal Sano Shunt in a Patient With Hypoplastic Left Heart Syndrome After Bidirectional Superior Cavopulmonary Connection.

The case describes the surgical treatment of a patient with a false aneurysm of the proximal anastomosis of the Sano shunt in a patient with hypoplastic left heart syndrome midterm after bidirectional cavo-pulmonary anastomosis. The diagnostic algorithm included a physical examination, echocardiography, and multispiral computed tomography. Surgical treatment included closure of the right ventricular defect and removal of blood clots from the cavity of the false aneurysm.

[Antibacterial effects of peptides synthesized based on the sequence of ribosome protein S1]. / Antibakterial'nye éffekty peptidov, sintezirovannykh na osnove posledovatel'nosti ribosomnogo belka S1.

Antibiotic resistance of bacteria is a topical problem on a global scale. Sometimes vigorous human activity leads to an increase in the number of bacteria carrying resistance genes in the environment. Antimicrobial peptides (AMPs) and similar compounds are potential candidates for combating antibiotic-resistant bacteria. Previously, we proposed and successfully tested on Thermus thermophilus a new mechanism of AMP action. This mechanism of directed coaggregation is based on the interaction of a peptide capable of forming fibrils with a target protein. In this work, we discuss the criteria for choosing a target for the targeted action of AMP, describe the features of the "parental" S1 ribosomal proteins T. thermophilus and Escherichia coli and the studied peptides using bioinformatic analysis methods, assess the antimicrobial effect of the synthesized peptides on a model organism of E. coli and cytotoxicity on cells of human fibroblasts. The obtained results will be important for the creation of new AMPs for pathogenic organisms.

Comparative Analysis of Aggregation of Thermus thermophilus Ribosomal Protein bS1 and Its Stable Fragment.

Functionally important multidomain bacterial protein bS1 is the largest ribosomal protein of subunit 30S. It interacts with both mRNA and proteins and is prone to aggregation, although this process has not been studied in detail. Here, we obtained bacterial strains overproducing ribosomal bS1 protein from Thermus thermophilus and its stable fragment bS1(49) and purified these proteins. Using fluorescence spectroscopy, dynamic light scattering, and high-performance liquid chromatography combined with mass spectrometric analysis of products of protein limited proteolysis, we demonstrated that disordered regions at the N- and C-termini of bS1 can play a key role in the aggregation of this protein. The truncated fragment bS1(49) was less prone to aggregation compared to the full-size bS1. The revealed properties of the studied proteins can be used to obtain protein crystals for elucidating the structure of the bS1 stable fragment.

Identification of Amyloidogenic Regions in the Spine of Insulin Fibrils.

To reveal conformational changes resulting in the formation of insulin fibrils, it is necessary to identify amyloidogenic regions in the structure of protein monomers. Different models of insulin fibrillogenesis have been proposed previously. However, precise regions responsible for the formation of amyloid fibrils have not been identified. Using bioinformatics programs for predicting amyloidogenic regions, we have determined some common amyloidogenic sequences in the structure of insulin monomers. The use of limited proteolysis and mass spectrometry analysis of the obtained protein fragments resistant to the action of proteases allowed us to identify amino acid sequences in the insulin structure that can form the spine of the insulin fibrils. The obtained results are in agreement with the earlier proposed model of fibril formation from the ring-like oligomers and can be used for designing insulin analogs resistant to amyloidogenesis.

Analysis of Insulin Analogs and the Strategy of Their Further Development.

We analyzed the structural properties of the peptide hormone insulin and described the mechanism of its physiological action, as well as effects of insulin in type 1 and 2 diabetes. Recently published data on the development of novel insulin preparations based on combining molecular design and genetic engineering approaches are presented. New strategies for creation of long-acting insulin analogs, the mechanisms of functioning of these analogs and their structure are discussed. Side effects of insulin preparations are described, including amyloidogenesis and possible mitogenic effect. The pathways for development of novel insulin analogs are outlined with regard to the current requirements for therapeutic preparations due to the wider occurrence of diabetes of both types.

[The Institutionalization of Traumatology and Orthopedics in Russia].

The article considers process of institutionalization of Russian traumatology and orthopedics. It is demonstrated that process of institutionalization goes on in undulating manner takes in average about 50 years, from the moment of statement of a question to ultimate assignment of specialty of traumatology and orthopedics, organization of institutes and chairs of traumotology and orthopedics with alternation of dominance of ducens- and mandate model. On the basis of developed criteria chronological clusters and periods. The selection of traumatology and orthopedics into independent field was related not to a transition to a new stage of development of science but to general process of increasing of differentiation and specialization in medicine.

Possible mechanisms for the effect of protein sensitization on functional properties of the isolated m. soleus and m. EDL from mice.

We studied possible involvement of ATP in the influence of protein sensitization on contractile function and non-quantum secretion in the end-plate of isolated skeletal muscles from mouse leg. The dynamic vector of muscle contraction force was shown to correlate with changes in non-quantum secretion of acetylcholine under various conditions of experimental pathology. However, the degree of these changes was lower in sensitized animals. It can be hypothesized that the ATP-induced variability in functional properties of slow muscles during protein sensitization reflects the development of resistance to external loads. The adaptive changes in fast muscles during protein sensitization are not associated with the ATP-mediated mechanisms of excitation.

Opposite effect of ATP on contraction force of tonic and phasic skeletal muscles in frogs.

Experiments in vitro showed that ATP and adenosine equally suppressed contractions of frog m. sartorius, which belongs to the phasic type muscles. Adenosine receptors antagonist 8-SPT abolished the effect of adenosine, but did not change the effect of ATP. This fact proves the independence of signaling pathways of these purines. ATP produced an opposite effect on the tonic muscle m. cruralis and increased the force of its contraction. Adenosine produced an inhibitory effect on the force of m. cruralis contration. In this case, 8-SPT also eliminated the effect of adenosine, but did not change the effect of ATP. The potentiating effect of ATP was blocked by suramin, a nonselective antagonist of P2 receptors, which attests to their involvement into the effects of this purine. The opposite effects of purinergic regulation reflect fundamental differences in functional organization of phasic and tonic muscular systems. It was hypothesized that the increase in contraction force under the effect of ATP is a mechanism providing maitenance of the contracted state of tonic muscle without appreciable metabolic costs.

Measurements of h(c)(1P(1)) in psi' decays.

We present measurements of the charmonium state h(c)(1P(1)) made with 106x10(6) psi' events collected by BESIII at BEPCII. Clear signals are observed for psi'-->pi0 h(c) with and without the subsequent radiative decay h(c)-->gamma eta(c). First measurements of the absolute branching ratios B(psi'-->pi0 h(c)) = (8.4+/-1.3+/-1.0) x 10(-4) and B(h(c)-->gamma eta(c)) = (54.3+/-6.7+/-5.2)% are presented. A statistics-limited determination of the previously unmeasured h(c) width leads to an upper limit Gamma(h(c))<1.44 MeV (90% confidence). Measurements of M(h(c)) = 3525.40+/-0.13+/-0.18 MeV/c2 and B(psi'-->pi0 h(c)) x B(h(c)-->gamma eta(c)) = (4.58+/-0.40+/-0.50) x 10(-4) are consistent with previous results.

Possible mechanisms for the effect of protein sensitization on contractile function of fast and slow muscles in mice.

We studied the mechanisms underlying the effect of immunobiological reorganization of the organism on contractile function of isolated skeletal muscles from mouse leg (fast muscle, m. extensor digitorum longus; and slow muscle, m. soleus). Protein sensitization was accompanied by changes in contractile properties of fast and slow skeletal muscles. These changes were differently directed in muscles with various phenotypes. The force of carbachol-induced contraction (cholinergic agonist) increased in the slow muscle, but decreased in the fast muscle. The direction of changes in the force of carbachol-induced contractions under conditions of protein sensitization in skeletal muscles correlates with changes in non-quantal secretion of acetylcholine in the endplate (H-effect). Opposite changes in functional properties of fast and slow muscles from mouse leg during protein sensitization are related to choline-mediated excitation of the muscle fiber membrane. Our results suggest that changes in contractile function of skeletal muscles during protein sensitization are associated with variations in choline-mediated excitation of the muscle fiber membrane and modification of electromechanical coupling.

[Ladasten, the new drug with psychostimulant and anxiolytic actions in treatment of neurasthenia (results of the comparative clinical study with placebo)].

An aim of a randomized blind study was to assess therapeutic efficacy and safety of ladasten used as an antiastenic drug in patients with neurasthenia. Tasks of the study included the investigation of characteristics of therapeutical actions, efficacy of the drug comparing to placebo, possible side-effects and probability of the development of "withdrawal syndromes". The design of the study included a wash-out period, a monotherapy with ladasten and placebo during 28 days and a final 1-week period of receiving placebo. Standartisized objective and subjective methods of mental state evaluation in patients were administered. The results obtained suggest that a combination of psychostimulant and anxiolytic actions in the spectrum of psychotropic activity of ladasten determines the its high therapeutic efficacy in asthenic disorders. It has been found that ladasten is superior in the rate and degree of reduction of main symptoms of asthenic syndrome compared to placebo. The absence of "withdrawal syndrome" after the drug withdrawal reveals the lack of addictive potential in this drug.

[Characteristics of ladasten effect in neurasthenia patients with various EEG parameters].

Clinical and electroencephalographic (EEG) analysis ofladasten action in anxiety-asthenic patients with respect to their EEG-defined individual typological characteristics was carried out. Primary psychopathologic disorders and ladasten effects were assessed by objective classification methods (factor and cluster analyses), and individual EEG types characterized by marked or reduced alpha rhythm were determined. No significant correlations between baseline EEG results and the initial mental condition indices were found. Significant differences ofladasten action in patients with different EEG types were found. It was established that, in patients with marked alpha rhythm corresponding to asthenic personal traits, ladasten exhibits predominantly a psychostimulant action assessed by clinical rating scales, which is accompanied by high frequencies of alpha rhythm increase and beta 1 and beta 2 rhythms decrease. In patients with reduced alpha rhythm and the EEG type corresponding to asthenic personal traits, ladasten action was characterized by an increase of alpha-rhythm low frequencies and the opposite reaction of beta 1 and beta 2 rhythms, whose are typical for the EEG pattern of anxiolytic effect. These results may indicate that the effect of ladasten depends on the initial brain activity level, which varies in patients with different individual typological traits.

Effect of GABAergic and adrenergic agents on activity of Na+/K+ pump and Cl(-)-cotransport in somatic muscle cells of earthworm Lumbricus Terrestris.

GABA, baclofen, epinephrine, and norepinephrine hyperpolarized the membrane of earthworm somatic cells. This effect was prevented by furosemide, removal of Cl- from the medium, or activation of Na+/K+ pump by 3-fold increase external potassium concentration. It was hypothesized that GABA, baclofen, epinephrine, and norepinephrine stimulate Na+/K+ transport via specific receptor inputs, but their effect on resting potential can be realized only under conditions of working Cl- symport.

Role of protein kinase C in the effect of ATP on contractile function of the isolated strip from mouse diaphragm.

We studied the effects of adenosine and ATP on contractile function of the isolated strip from mouse diaphragm. ATP significantly increased the strength of muscle contraction induced by carbachol. Adenosine had no effect on carbachol-induced muscle contraction. P2 receptor antagonist suramin abolished the effect of ATP. The positive chronotropic effect of ATP was not observed after treatment with specific protein kinase C inhibitor chelerythrine. Our results indicate that the effect of ATP on contractile function of mouse diaphragm is realized via protein kinase C.

Mechanism of N-ethylmaleimide-induced contraction of the frog sartorius muscle.

We studied parameters of the frog sartorius muscle contraction initiated by ryanodine receptor agonists in the presence of ROS donors. We hypothesized that sodium nitroprusside and hydrogen peroxide inhibit initiation of contractions by N-ethylmaleimide and that this effect of ROS donors on parameters of N-ethylmaleimide-induced contractions is due to a direct effects of sodium nitroprusside and hydrogen peroxide on N-ethylmaleimide, but not to inactivation of ryanodine receptors in the sarcoplasmatic reticulum of frog skeletal muscle.

[Pilot clinical trial of ladasten].

The psychotropic actibn and efficacy of ladasten, a new psychostimulant with anxiolitic activity, was studied in a standard clinical trial involving therapy of patients with psychogenic asthenic disorder. Ladasten exhibits a unique combination of therapeutically significant stimulant and anxiolytic effects, which is unusual of psychostimulants. At the same time, the results of ladasten action upon single administration on the dynamics of psychopatological disorders and psychological self-test indexes show that the psychostimulant action is predominating. The established combination of the psychostimulant and anxiolytic effects of ladasten is optimal for the therapy of patients with psychogenic asthenic disorders. Ladasten shows high efficacy in the treatment of these disorders testify and has good prospects for practical application.

The presynaptic effects of arachidonic acid and prostaglandin E2 at the frog neuromuscular junction.

Arachidonic acid and prostaglandin E2 decreased the frequency of miniature endplate potentials with producing any changes in the their amplitude-time parameters. Arachidonic acid and prostaglandin E2 decreased the quantum composition of endplate currents and the amplitude of the third phase of the nerve ending response, which reflects currents though potential-dependent K+ channels. A perineural method was used to demonstrate that arachidonic acid and prostaglandin E2 suppressed the nerve ending Ca2+ current. The cyclooxygenase blocker indomethacin increased neurotransmitter secretion and decreased the third phase of the nerve ending response. The effects of arachidonic acid and prostaglandin E2 on evoked neurotransmitter release were not seen in the presence of indomethacin, while the third phase of the response continued to show a reduction. It is suggested that prostaglandin E2 mediates the effects of arachidonic acid on spontaneous and evoked neurotransmitter secretion, Ca2+ currents, and Ca2+ -dependent K+ currents. In addition, arachidonic acid and prostaglandin E2 had their own effects on potential-dependent K+ currents in nerve endings.

Mechanisms of hyperpolarizing effect of GABA on resting potential of the Lumbricus terrestris muscular wall somatic cells.

GABA, baclofen, isoguvacine increase, and cis-4-aminocrotonic acid does not modify resting membrane potential of muscle cells. Bicuculline, phaclofen, N-ethylmaleimide, chlorpromazine, verapamil, and removal of Ca2+ from bathing solution abolished the effect of baclofen, while U73122 and D609 were ineffective in this respect. The authors conclude that the Lumbricus terrestris muscle cells contain GABAergic structures similar to a- and b-receptors. Activation of GABA receptors induced Cl- inward current and Ca2+ entry with subsequent activation of calmodulin-like proteins, which causes membrane hyperpolarization by increasing the effect of "pumping potential" on resting membrane potential.