[Use of endovascular drug-coated devices in lesions of femoropopliteoltibial arteries]. / Ispol'zovanie éndovaskuliarnykh ustroistv s lekarstvennym pokrytiem pri porazhenii arterii bedrenno-podkolenno-bertsovogo segmenta.

Endovascular intervention is one of the main methods of treatment in atherosclerotic lesions of the infrainguinal segment in patients with chronic lower limb ischaemia. Recent years have witnessed active use of drug-eluting techniques, significantly improving the long-term outcomes of peripheral reconstructions. This article is a review of publications on the results of using modern drug-eluting balloon catheters and stents in the femoropopliteoltibial position. The accumulated data will help solve the main problems of the classic balloon angioplasty, reducing the incidence of restenosis, improving primary patency, and decreasing the need for repeat interventions in the remote period of follow-up.

[Comparison of efficacy of rivaroxaban and warfarin after open operations on the infrainguinal segment]. / Sravnenie éffektivnosti rivaroksabana i varfarina posle otkrytykh operatsii na infraingvinal'nom segmente.

The authors analysed oral anticoagulant agents prescribed in the postoperative period to patients after endured reconstructive operative intervention on arteries of the femorotibial segment. The study included a total of 104 patients subjected to femoropopliteal or femorotibial bypass grafting using an autologous vein or a prosthesis. Depending on the prescribed anticoagulation agent, the patients were subdivided into two groups. Group One patients (n=43) in the postoperative period received rivaroxaban, and Group Two patients (n=61) took warfarin. Efficacy of therapy was evaluated by the frequency of haemorrhage and thromboses in the early and remote postoperative periods. The findings of the immediate postoperative period demonstrated comparable rates of haemorrhagic complications, early thromboses and redo interventions in both Groups (p=0.7). The duration of long-term postoperative period varied from 3 months to 5 years. No statistically significant differences in patency of the performed reconstructions were revealed between the groups. The 3-year primary assisted patency rate in the rivaroxaban group and warfarin group amounted to 89 and 80%, respectively. The incidence of haemorrhagic complications in the postoperative period was insignificant in the studied groups. Hence, rivaroxaban may be prescribed in the early and remote postoperative period to patients who underwent open reconstructive operative intervention on arteries of the infrainguinal zone.

[Results of hybrid loop endarterectomy from the superficial femoral artery with the MultiTASC]. / Rezul'taty gibridnoi petlevoi éndarteréktomii iz poverkhnostnoi bedrennoi arterii petlei MultiTASC.

The purpose of this study was to analyse the results of hybrid loop endarterectomy from the superficial femoral artery (SFA) in its occlusion, preformed in a total of forty-two patients. Of these, 27 patients had prior to the intervention been diagnosed with stage II B ischaemia and 15 patients had been diagnosed as having critical ischaemia. Technical success of the operation amounted to 88%, with the frequency of early thromboses equalling 2.7%. In the early postoperative period, one patient died of acute myocardial infarction. The 1-, 2- and 3-year remote cumulative primary patency rate amounted to 81, 74 and 74%, respectively. There were no amputations performed within the timeframe of the follow-up period. The technique of hybrid loop endarterectomy with the MultiTASC loop followed by stenting of the proximal portion of the popliteal artery in occlusion of the SFA and stenoses of the common femoral artery has proved to be a highly efficient intervention yielding good immediate and remote results.

Long-term hyperthermia impairs activity of both photosystems.

This is the first study to perform a simultaneous analysis of the activity of photosystem 1 and photosystem 2 after long-term exposure to elevated temperature. It was found that the quantum yield of photochemical reactions decreases in both photosystems. It is shown that, in photosystem 2, the regulated nonphotochemical quenching decreases whereas the unregulated non-photochemical quenching increases. In photosystem 1, limitation on both acceptor and donor sides increases.

Signaling targets of alcoholic intoxication in human skeletal muscle.

Intracellular signaling pathways were investigated in skeletal muscle cells at the early stages of alcohol addiction manifestations. No muscle fiber atrophy was observed in m. vastus lateralis of male patients. No significant changes in the signaling mechanisms that control protein degradation were detected as well. However, the concentration of the insulin-like growth factor (IGF-1) in blood plasma as well as the content of markers of intracellular signaling pathways regulating protein synthesis were significantly reduced compared to the control group.

[Effect of Combined Aerobic and Strength Exercise on Regulation of Mitochondrial Biogenesis, Protein Synthesis and Degradation in Human Skeletal Muscle.]

We tested the hypothesis that strength exercise after intermittent aerobice exercise might activate signalling pathways related to mitochondrial biogenesis (phosphorylation level of AMPK, p38; expression of PGC-1a, NT-PGC-la, TFAM, VEGFA), to protein synthesis (phosphorylation level of p70S6Kl(Thr389) eEF2(Thr56) expression of IGF-lEa, IGF-lEc (MGF), REDDl) and to proteolysis (phosphorylation level of FOXOl(Ser256) and expression of MURFl, MAFbx, Myostatin) in trained skeletal muscle. Nine amateur endurance-trained athletes performed 70-Min bicycle intermittent exercise with both legs (E), followed by one-leg strength exercise (ES: 4 bouts of knee extensions at 75% MVC till exhaustion). Gene expression and protein level were evaluated in samples from m. vastus lateralis before, 40 min, 5 and 22 h after the aerobic exercise. The phosphorylation level of the ACC(Ser79/222)(an endogenous marker of AMPK activity) and expression of PGC-la-related TFAM - marker of mitochondrial biogenesis were increased after E exercise and did not changed after ES. Expression of PGC-lα and truncated isoform NT- PGC-lα was increased in both legs as well. Insulin concentration in blood was dramatically, 7.5-fold diminished after intermittent aerobic exercise. Phosphorylation of FOXO(Ser256) - regulator of ubiquitin-related proteolysis - was decreased after both E and ES exercise, it means it was activated in both cases, while expression of E3-ubiquitin ligase MURFl was increased only after E exercise. Both aerobic and combined exercise did not affect regulation of protein synthesis: neither expression of IGF-lEa and IGF-Ec (MGF) mRNA isoforms nor phosphorylation levels of markers of protein synthesis p70S6Kl(Thr389) and eEF2(Thr56) were changed. Thus effects of aerobic exercise in trained muscles are noticeably suppressed by performing strength exercise immediately after endurance one. In particular, the activity of signalling cascades and expression of genes regulating mitochondrial biogenesis are lessened, but protein synthesis regulation is not affected. And at last strength exercise suppresses induced by aerobic exercise expression of MURF1 gene - marker of ubiquitin proteasome system. It means that strength exercise just after intermittent aerobic exercise might have a negative effect on aerobic performance if used chronically.

On the mechanism of erythrocyte hemolysis induced by photooxidized psoralen.

Contemporary concepts on a possible mechanism of erythrocyte hemolysis induced by photooxidized psoralen - the medicinal photosensitizing furocoumarin - are reviewed. The hypothesis on the mechanochemical mechanism of hemolysis is considered in view of recent data on photoinduced aggregation in photooxidized psoralen solutions. Appropriate chemical structures of photoproduct hemolysins and aggregating photoproducts are discussed.

[The Effect of Single Aerobic Training on the Regulation of Mitochondrial Biogenesis in Skeletal Muscles of Trained Men: a Time-Course Study].

Adaptation of skeletal muscles to physical training depends on intensity and duration of exercise sessions. The purpose of this study was to investigate the effect of the duration of moderately intensive single aerobic exercise session (60% V(O2max)) on the activation of signalling kinases which regulate PGC-1α gene expression and on the expression of regulatory genes of mitochondrial biogenesis and muscle catabolism. Nine athletes (V(O2max)) 59 mL/min/kg) performed 30-, 60-, and 90-min cycling sessions. An exercise-induced increase in PGC-1α gene expression was proved to occur without activation of AM PK, p38 MAPK and CAMKII. It was found that 60- and 90-min sessions result in comparable increases of PGC-lα gene expression, while VEGFA gene expression increased only after 90-min session. Even 90-min exercise did not induce the activation of FOXO1-E3 ubiquitin ligase pathway and did not result in an increase of expression of exercise-induced catabolic genes.

Regulation of PGC-1α Isoform Expression in Skeletal Muscles.

The coactivator PGC-1α is the key regulator of mitochondrial biogenesis in skeletal muscle. Skeletal muscle expresses several PGC-1α isoforms. This review covers the functional role of PGC-1α isoforms and the regulation of their exercise-associated expression in skeletal muscle. The patterns of PGC-1α mRNA expression may markedly differ at rest and after muscle activity. Different signaling pathways are activated by different physiological stimuli, which regulate the expression of the PGC-1α gene from the canonical and alternative promoters: expression from a canonical (proximal) promoter is regulated by activation of the AMPK; expression from an alternative promoter, via a ß2-adrenergic receptor. All transcripts from both promoters are subject to alternative splicing. As a result, truncated isoforms that possess different properties are translated: truncated isoforms are more stable and predominantly activate angiogenesis, whereas full-length isoforms manly regulate mitochondrial biogenesis. The existence of several isoforms partially explains the broad-spectrum function of this protein and allows the organism to adapt to different physiological stimuli. Regulation of the PGC-1α gene expression by different signaling pathways provides ample opportunity for pharmacological influence on the expression of this gene. Those opportunities might be important for the treatment and prevention of various diseases, such as metabolic syndrome and diabetes mellitus. Elucidation of the regulatory mechanisms of the PGC-1α gene expression and their functional role may provide an opportunity to control the expression of different isoforms through exercise and/or pharmacological intervention.

[THE INDICATORS OF GROWTH AND MYOGENESIS IN THE GLYCOLYTIC AND OXIDATIVE MUSCLES OF THE RAT AFTER INDIRECT ELECTROSTIMULATION].

A comparative analysis of the signaling pathways activity and gene expression in the red (RG) and white (WG) parts of the gastrocnemius muscle of rat after a series of short (1 s) tetanic contractions induced by motor nerve stimulation at a frequency of 100 Hz and with an amplitude that provides activation of all motor units of the muscle. WG compared to RG demonstrated a marked increase in the phosphorylation level of ERK1/2, although the increase in the phosphorylation of AMPK was not different in two muscles 2 h after the stimulation. Along with that, content of MyoD and myogenin mRNA in WG increased much higher than in RG, whereas the effect of stimulation on IGF-1, MaFbx and MuRF genes expression was weak and comparable in WG and RG. There was an increase of myostatin mRNA in RG. Thus, glycolytic muscle fibers of WG exhibit more pronounced regulatory shifts of hypertrophic character than oxidative muscle fibers of RG.

[Regional differences in the level of ERK1/2 phosphorylation and expression of the myogenic regulatory factors following electrostimulation with different mechanic and metabolic action on the gastrocnemius muscle].

Effect of high-frequency electrical stimulation of the sciatic nerve on ERK1/2 kinase phosphorylation and mRNA expression in MyoD (myogenic regulation factor) and myogenin in the red (RGM) and white (WGM) parts of the medial head in rat's m. gastrocnemius was studied. Two stimulation regimes were equalized both lengthwise and in total effort but differed in duration and number of contractions and, therefore, in mechanic and metabolic effects on the muscle. It was shown that growth of the number of phosphorylated ERK1/2 was particularly high in WCM due to application of the protocol for multiple short-time contractions. Whatever the stimulation regime, MyoD mRNA expression in RGM and WGM increases to the same extent, whereas myogenin mRNA expression does not change. Consequently, the regime with the predominantly mechanic effect is favorable to activation of the ERK signaling pathway in glycolytic myofibers.

[Effect of branched-chain amino acids mixture on repair of atrophied rats' skeletal muscles].

Loss of muscle mass (atrophy) is a regular consequence of gravitational unloading. In hypogravity, muscle atrophy ensues from depression of protein synthesis and increase of its degradation. Both of these processes underlie also atrophy caused by muscle immobilization, cancer cachexia, cardiomyopathy and age-related sarcopenia. At the same time, atrophy of skeletal muscles due to chronic alcohol intoxication is the outcome of protein synthesis depression primarily. The study was part of a program aimed to develop a technique for atrophied muscle recovery by activation of anabolic signal pathways. A similar approach is applied to correct hypogravity-induced atrophy; however, analysis of effectiveness of this approach to the treatment of alcoholic muscle atrophy will be more "pure", as proteolytic processes in intoxicated animals are on the level typical of the intact ones. The issue in hand was whether injection of branched-chain amino acids (BCAA) would facilitate repair of m. gastrocnemius medialis in rats in the period of 30 days after 16-week alcoholic intoxication. BCAA was shown to enhance regain size by fast muscular fibers, full recovery of phosphorylated p90RSK concentrations without consequential effects on general proliferative processes and myonuclear number in rat's m. gastrocnemius medialis.

[The study of intron containing pre-mRNA and spliced mRNA in maize chloroplasts with the use of RT-PCR].

The study of chloroplast RNA splicing is usually performed by such complicated methods as Northern blot hybridization, RNAse protection or primer extension. An application of simpler RT-PCR technique may lead to underestimation of unspliced pre-mRNA. We used five protein coding genes from maize plastome to analyze factors that can reduce a pool ofintron containing transcripts as compared to a mature RNA. We revealed that a mode of DNAse inactivation, a temperature of cDNA synthesis, and a type of DNA polymerase used are important for the proper detection of unspliced RNA level. The increase in a number of PCR cycles was accompanied with a concomitant decrease in the proportion of unspliced RNA for a one gene only. We demonstrated that after PCR intron containing and intron free strands of amplicons are able to form heteroduplexes. The information obtained let us to introduce the simple and effective method for the investigation of a chloroplast spliced mRNA and unspliced pre-mRNA.

[Outcomes of hybrid operations in multi storeyed lesions of arteries of the aortoiliac and femoropopliteal segments].

The work was aimed at analysing immediate and remote outcomes of hybrid operations in storey atherosclerotic lesions of the aortoiliac and femoropopliteal segments. Over the period from 1997 to 2012 hybrid operations were performed in a total of 224 patients presenting with multi-storeyed lesions of iliac and lower-limb arteries, classified as TASC A, B, C, and D. The operations were carried out at departments of vascular surgery of Clinical Hospital No 83 of the Federal Biomedical Agency of Russia and the Centre of Cardiovascular and Endovascular Surgery of Clinical Hospital No 119 of the Federal Biomedical Agency of Russia. All operations were simultaneous. The patients were subdivided into groups according to the character of intervention on iliac arteries: 1 - balloon angioplasty of iliac arteries, 2 - stenosing of iliac arteries, 3 - loop endarterectomy from iliac arteries followed by implantation of a covered stent into the zone of rupture of the intimal cylinder. In all cases the interventions of the arteries of the aortoiliac segment were combined with various open surgical reconstructions of the femoropopliteal segment. Technical success amounted to 99.1%. Interventional complications of the endovascular stage requiring conversion occurred in 2 cases. The immediate period complications influencing patency of the reconstructions performed were noted in 10 (4.5%) patients. Patency on the hospital stage with the deduction of cases of technical failures amounted to 98.6%. The remote results were followed up during 5 years in 76.5% of patients. Five-year primary assisted patency of the aortoiliac zone amounted to: in group 1 - 79.2%, in group 2 - 77.9%, and in group 3 - 89.4%. Five-year assisted patency of the femoropopliteal segment amounted to: for EAE of the common femoral artery - 98.2%, for profundoplasty - 100%, femoral proximal popliteal bypass grafting - 77.3%, femoral distal popliteal bypass grafting - 74.1%, femoral-tibial bypass grafting - 61.4%. There were no statistically significant differences in patency of the reconstructions of the femoropopliteal segment depending upon the type of intervention on the aortoiliac segment.

[Optimization of training: development of a new partial load mode of strength training].

Hypertrophic effect of strength training is known to originate from mechanical and metabolic stimuli. During exercise with restricted blood supply ofworking muscles, that is under conditions of intensified metabolic shifts, training effect may be achieved with much lower external loads (20% of one repetition maximum (1 RM)). The aim of the study was to compare the effects of 8 wks high-intensity (80-85% MVC) strength training and low-intensity (50% 1 RM) training without relaxation. The high-intensity strength training leads to somewhat higher increments in strength and size of trained muscles than training without relaxation. During high-intensity training an increase of area occupied by type II fibers at muscle cross section prevails while during training without relaxation - an increase of area occupied by type I fibers takes place. An exercise session without relaxation leads to a more pronounced increase in secretion of growth hormone, IGF-1 and cortisol. Expression of gene regulating myogenesis (Myostatin) is changed in different ways after high-intensity strength exercise session and after exercise session without relaxation. Low-intensity strength training (50% 1 RM) without relaxation is an effective way for inducing increases of strength and size of trained muscles. This low intensive type of training may be used in restorative medicine, sports and physical culture.

[Proteolytic signaling mechanisms in skeletal muscles in patients with alcohol-induced muscle disease].

Chronic alcoholic myopathy is one of most numerous and profound manifestations of chronic alcohol intoxication. This disease is characterized by the pronounced atrophy of the locomotor muscles, which involves predominantly those fibers expressing myosin isoforms of the I "fast" type. In early experiments with alcohol-fed rats and studies of patients it was shown the impairment of the anabolic intracellular signaling pathways and decrease in protein synthesis rate. We were the first to analyze the signaling pathways involved in the pathogenesis of alcoholic myopathy with different fiber atrophy levels. At the early stages of the pathogenesis we observed also the sufficient increase of mRNA of E3 ubiquitin ligases. However the ubiquitinylation level was not altered in patients as compared to the control subjects. This phenomenon could be associated with the increased expression of the heat-shock proteins, known for their protective action.

[Effects of recombinant mechano-dependent growth factor against the background of chronic alcoholisation in rats].

In alcoholised rats, proliferation of satellite cells consistently decreased as well as the number of myonuclei, while phosphorylation of p90RSK became reduced. The mechano-growth factor abministration increased the proliferate activity of the myogenic precursors and restored the myonuclei pool. Phosphorylation of p90RSK increased too.

Role of NO-synthase in regulation of protein metabolism of stretched rat m. soleus muscle during functional unloading.

Gravitational unloading causes atrophy of muscle fibers and can lead to destruction of cytoskeletal and contractile proteins. Along with the atrophic changes, unloaded muscle frequently demonstrates significant shifts in the ratio of muscle fibers expressing fast and slow myosin heavy chain isoforms. Stretching of the m. soleus during hindlimb suspension prevents its atrophy. We supposed that neuronal NO-synthase (NOS) (which is attached to membrane dystrophin-sarcoglycan complex) can contribute to maintenance of protein metabolism in the muscle and prevent its atrophy when m. soleus is stretched. To test this hypothesis, we used Wistar rats (56 animals) in experiments with hindlimb suspension during 14 days. The group of hindlimb suspended rats with stretched m. soleus was injected with L-NAME to block NOS activity. We found that m. soleus mass and its protein content in hindlimb-suspended rats with stretched m. soleus were preserved due to prevention of protein degradation. NOS is involved in maintenance of expression of some muscle proteins. Proliferation of satellite cells in stretched m. soleus may be due to nNOS activity, but maintenance of muscle mass upon stretching is regulated not by NOS alone.

Protective effect of L-Arginine administration on proteins of unloaded m. soleus.

Cytoskeletal and contractile proteins degenerate during functional unloading of muscle. The ratio of myosin heavy chain (MHC) expression changes simultaneously. We have supposed that NO can be a signal molecule related to the regulation of protein metabolism upon muscle unloading. To test this hypothesis, Wistar rats underwent functional unloading for 14 days without and with peroral administration of L-arginine (500 mg/kg) as NO precursor. Significant decreases in m. soleus mass, NO, nNOS, dystrophin, Hsp90, p-S6K, and type I MHC mRNA contents were found in the group of animals with unloading without preparation compared to those in control and in the group with unloading and administration of L-arginine; at the same time, increased contents of atrogin-1/MAFbx and MuRF-1 (p < 0.05) were found. No difference in the IGF-1 mRNA content between all three groups was found. Atrophy was significantly less pronounced in the group with unloading and L-arginine administration compared to that without the amino acid, and no destruction of cytoskeletal proteins was observed. We conclude that administration of L-arginine upon functional unloading decreases the extent of m. soleus atrophy, prevents the decrease in it of type I MHC mRNA, and blocks destructive changes in some cytoskeletal proteins. Such effect can be due to the absence of increase in this group of the content of some ubiquitin ligases and decreased intensity of the p70S6 kinase synthesis marker.